facial soft-tissue fillers conference: assessing the state of the … · 2020. 8. 18. · groups...

Facial Soft-Tissue Fillers conference: Assessing theState of the Science

C. William Hanke, MD, Rod J. Rohrich, MD,

Mariano Busso, MD, Alastair Carruthers, MA, BM, BCh, Jean Carruthers, MD, Steven Fagien, MD,

Rebecca Fitzgerald, MD, Richard Glogau, MD, Phyllis E. Greenberger, MSW, Z. Paul Lorenc, MD,

Ellen S. Marmur, MD, Gary D. Monheit, MD, Andrea Pusic, MD, MHS, Mark G. Rubin, MD,Berthold Rzany, MD, ScM, Anthony Sclafani, MD, Susan Taylor, MD, Susan Weinkle, MD,

Michael F. McGuire, MD, David M. Pariser, MD, Laurie A. Casas, MD, Karen J. Collishaw, Roger A. Dailey, MD,

Stephen C. Duffy, Elizabeth Jan Edgar, MS, Barbara L. Greenan, Kelly Haenlein, MHA,

Ronald A. Henrichs, CAE, Keith M. Hume, MA, Flora Lum, MD, David R. Nielsen, MD,

Lisle Poulsen, Lori Shoaf, JD, William Seward, MA, Wendy Smith Begolka, MS,

Robert G. Stanton, Katherine J. Svedman, CAE, J. Regan Thomas, MD, Jonathan M. Sykes, MD,

Carol Wargo, MA, and Robert A. Weiss, MD

Dallas, Texas, and Carmel, Indiana

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Summary: The American Academy of Dermatology and the American Society of Plastic Surgeons, with thesupport of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Scienceconference in December of 2009. The American Academy of Dermatology and the American Society ofPlastic Surgeons established a panel of leading experts in the field of soft-tissue fillers—from researchers toclinicians—and other stakeholders for the conference to examine and discuss issues of patient safety,efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and otherfactors, including the training and level of experience of individuals administering fillers. This reportrepresents the systematic literature review that examines comprehensively the available evidence and gapsin the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-scienceconference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field. ( J Am Acad Dermatol 2011;64:S66-85.)

In November of 2008, the U.S. Food and DrugAdministration’s General and Plastic SurgeryPanel held a meeting to receive an ‘‘update on

safety information collected on dermal fillers in thecommercial setting, discuss current premarket andpostmarket approved study designs, and make rec-ommendations on general issues concerning the

the Department of Plastic Surgery, University of Texas

edical Center, and the Department of Dermatology, Saint

ncent Carmel Medical Center, Laser and Skin Surgery Center

Indiana.

ared for the American Academy of Dermatology and the

merican Society of Plastic Surgeons and by The Lewin Group.

osures: Rod J. Rohrich, M.D., declares he is the recipient of

search grant funds received by the University of Texas South-

estern Medical Center from Medicis, Contura, Mentor (dermal

lers or botulinum toxin type A studies), and Baxter (fibrin

alant study). C. William Hanke, M.D., declares financial interest

a shareholder in Medicis and Allergan. In addition, he declares

ving been the recipient of research support from Medicis,

llergan, Merz, Dermik, and Galderma. For additional disclosure

formation, please see the Disclosure Appendix in this issue.

supplement in its entirety is jointly published by the Journal

the American Academy of Dermatology and Plastic and

constructive Surgery.

ion of the articles in the JAAD follows this format: Hanke CW,

hrich RJ, Busso M, Carruthers A, Carruthers J, Fagien S, et al.

cial Soft-Tissue Fillers: Assessing the State of the Science

study of various dermal fillers.’’1 They are cited inbrackets at the end of the article for programmaticreasons only. A complete summary of this meeting isprovided.1

In response to the rapidly growing use of soft-tissue fillers and the findings of the U.S. Foodand Drug Administration panel, the following

conference—Proceedings report. J Am Acad Dermatol 2011;64

(Suppl):S53-65.

Citation of the articles in PRS follows this format: Rohrich RJ, Hanke

CW. Facial Soft-Tissue Fillers: Assessing the State-of-the-Science

Conference—Proceedings Report. Plast Reconstr Surg 2011;127

(Suppl 2):9S-21S.

Received for publicationMay 25, 2010; accepted November 5, 2010.

Correspondence to: Rod J. Rohrich, M.D., Department of Plastic

Surgery, University of Texas Southwestern Medical Center, 1801

Harry Hines Boulevard, Dallas, Texas 75390-9132, E-mail:

[email protected] or C. William Hanke, M.D.,

Department of Dermatology, Saint Vincent Carmel Medical

Center, Laser & Skin Surgery Center of Indiana, 13400 North

Meridian Street, Suite 290, Carmel, Ind. 46032 E-mail:

[email protected].

0190-9622/$36.00

� 2011 by the American Academy of Dermatology, Inc and

Copyright � 2011 by the American Society of Plastic Surgeons.

doi:10.1016/j.jaad.2011.02.009

mailto:[email protected]

mailto:[email protected]

http://dx.doi.org/10.1016/j.jaad.2011.02.009

Table I. PubMed literature search strategy

Concept Search string Hits

General terms fordermal fillers

‘‘dermal filler*’’ [tiab] OR ‘‘soft tissue filler*’’ [tiab]OR ‘‘soft-tissue filler*’’ [tiab] OR ‘‘injectablefiller*’’ [tiab] OR ‘‘wrinkle filler*’’ [tiab] OR ‘‘skinfiller*’’ [tiab] OR ‘‘facial filler*’’ [tiab] OR‘‘collagen* filler*’’ OR ((‘‘cosmetic techniques’’[MH] OR ‘‘rejuvenation’’ [MH]) AND (‘‘collagen’’[MH] OR ‘‘hyaluronic acid’’ [MH] OR ‘‘lactic acid’’[MH] OR ‘‘durapatite’’ [MH] OR ‘‘polymethylmethacrylate’’ [MH] OR ‘‘silicone oils’’ [MH]))

OR AND 621

Collagen fillers ‘‘cosmoderm’’ OR ‘‘cosmoplast’’ OR ‘‘cymetra’’ OR‘‘fascian’’ OR ‘‘zyderm’’ OR ‘‘zyplast’’ OR‘‘glutaraldehyde-cross-linked collagen’’ OR‘‘evolence’’

Hyaluronic acid fillers ‘‘juvederm’’ OR ‘‘perlane’’ OR ‘‘restylane’’ OR hylan-B gel [Substance Name] OR ‘‘hylaform’’ OR‘‘puragen’’ OR ‘‘captique’’

Poly-L-lactic acid fillers ‘‘sculptra’’ OR ‘‘new-fill’’ [Substance Name]Calcium hydroxylapatite fillers ‘‘radiesse’’Polymethyl methacrylate fillers ‘‘artefill’’Limits (humans[MH] AND English[lang] NOT (editorial[pt] OR letter[pt] OR

comment[pt]) NOT (review[pt] NOT (review[pt] AND (systematic[tiab]OR comprehensive[tiab] OR method*[tiab] OR medline*[tiab] ORpubmed*[tiab])))

The asterisk (*) is a ‘‘truncation symbol’’ or ‘‘wildcard,’’ which means that any characters that come after it are retrieved, including those with

no other characters. The quotation marks (‘‘ ’’) mean that the search looked for the words as a phrase. The [tiab] means the search looked for

the indicated term in the title or abstract. A search term with the [MH] after the term does not have the asterisk because it is a set MeSH

thesaurus term and will not have any variations.

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VOLUME 64, NUMBER 4Hanke et al S67

groups convened the Facial Soft-Tissue Fillers:Assessing the State of the Science conferenceon December 6 through 7, 2009, in Washington,D.C.:

d AmericanAcademyofDermatology (sponsor society)d American Academy of Facial Plastic and Recon-structive Surgery (supporting society)

d American Academy of Ophthalmology (support-ing society)

d American Academy of OtolaryngologyeHead andNeck Surgery (supporting society)

d American Society for Aesthetic Plastic Surgeons(supporting society)

d American Society for Dermatologic Surgery (sup-porting society)

d American Society of Plastic Surgeons (sponsorsociety)

Please see the companion article that summarizesthe conference proceedings. The purpose of thissystematic literature review is to examine compre-hensively and assess the available evidence and gapsin the evidence related to soft-tissue fillers to informand support the work of the state-of-the-scienceconference panel.

METHODOLOGYSearch strategy

A comprehensive search strategy was developedto search PubMed, which includes access toMEDLINE, and citations for selected articles in lifescience journals not included in MEDLINE. Thesearch strategy was designed to ensure broad cap-ture of all relevant articles. Search strings using MeSH(Medical Subject Headings, PubMed’s controlledvocabulary for indexing studies) terms and key textterms were combined to produce the resultingsearch strategy. Varied constructs of search termswere captured with the use of truncation (repre-sented by an asterisk). Additional parameters werealso applied to the search strategy, including limitingretrieval to articles with abstracts in English, andfocused on humans. Using the date limit functionwithin PubMed, we limited our search to studiespublished since January 1, 1994. We also used a limitfunction in PubMed to exclude letters, editorials, andcommentaries. Table I lists the search terms andparameters we applied. This search yielded a total of621 abstracts.

We conducted a title and abstract review ofthese studies, applying inclusion/exclusion criteria

Table II. Inclusion/exclusion criteria forabstract/title review

Included study typesMeta-analysisSystematic reviewClinical trialRandomized controlled trialControlled clinical trialUncontrolled clinical trial

Epidemiologic studyCohort studyCase-control studyCross-sectional studyFollow-up studyEvaluation study

Case report/seriesExcluded study types*Nonsystematic reviewsGuidelines

Included treatment typesSoft-tissue fillers, including the following:CollagenHyaluronic acidPoly-L-lactic acidCalcium hydroxylapatitePolymethylmethacrylateSilicone oil fillers

Polyacrylamide gelsExcluded treatment typesBotulinum toxinPolymers and collagen-related implantsDermal stimulators

*Particularly informative reviews and guidelines were retained to

inform the background section.

Table III. Full-text studies by type of study andtype of soft-tissue filler

Type of study Collagen HA PLLA CaHA PMMA Other Total*

SR 0 1 1 0 0 2 4RCT 13 25 2 3 2 1 33CCT 2 0 0 0 0 0 2UCT 1 13 4 15 0 8 41Cohort 1 4 7 2 1 4 18Cross-sectional 0 1 0 1 0 1 3Case series 17 39 19 11 10 20 97Total 34 83 33 32 13 36 198

HA, Hyaluronic acid; PLLA, poly-l-lactic acid; CaHA, calcium

hydroxylapatite; PMMA, polymethylmethacrylate; SR, systematic

review; RCT, randomized controlled trial; CCT, controlled clinical

trial; UCT, uncontrolled clinical trial.

*Citations pertaining to more than one soft-tissue filler type within

a study are counted for soft-tissue filler, but only once for the

‘‘Totals’’ column.

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APRIL 2011S68 Hanke et al

developed in collaboration with the SteeringCommittee and based on study type and treatmenttype. These inclusion/exclusion criteria are pre-sented in Table II. The review of title and abstractsyielded a total of 213 potentially relevant studies.Full-text articles for these studies were ordered andcarefully reviewed, and a precise classification ofeach of the articles was performed. After the full-textreview, a total of 198 unique, relevant studies wereidentified for inclusion in this review.

Although case reports and small case series stud-ies are not typically included in an evidence review,we reviewed these study types for this report basedon the assumption that there is little information onadverse events associated with use of soft-tissuefillers in general. Case reports and case series,though methodologically limited, are importantsources of adverse event data, which are of highpriority for evaluating soft-tissue fillers. Table IIIsummarizes the distribution of the articles identifiedby study design and soft-tissue filler type.

Data abstraction and gradingTo capture information from the included studies,

data abstraction forms were developed in aMicrosoftAccess (Microsoft Corp., Redmond, Wash.) database.Trained abstractors reviewed full-text versions ofeach in-scope study and recorded key study datausing the forms, including basic information aboutthe study (e.g., year of publication), patient popula-tion, intervention, outcomes measured, results, andadverse events. Drawing from the data abstracted inthe forms, the Access database was used to createevidence tables by soft-tissue filler type. Studiesaddressing more than one soft-tissue filler type arecounted for each type, as relevant. Evidence tablesfor all included studies can be found in AppendixA (available at http://www.eblue.org). Figure 1 out-lines the phases of the literature review process andthe number of studies excluded at each stage.

In addition to abstraction of relevant data fromeach study, studies were assessed for their quality.Assessing the quality of individual studies helps todetermine and characterize the overall strength of abody of evidence for a given research question ortopic. To provide a quality grade or rating to eachstudy, we adapted quality assessment methods usedby the Agency for Healthcare Research and QualityEffective Health Care Program, which essentiallyinvolves three stages: (1) classify the study design;(2) apply predefined criteria for quality and criticalappraisal; and (3) arrive at a summary judgment ofthe study’s quality.2

After classifying the study designs and abstractingrelevant data from the 198 included studies, weapplied 11 predetermined criteria, which we adap-ted from the Agency for Healthcare Research and

http://www.eblue.org

Fig 1. Literature review flow diagram.

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Quality Methods Reference Guide, to form a judg-ment about the validity of each study’s results. TableIV presents these criteria.

Although some of these criteria are straightfor-ward, others require consideration of the specificcharacteristics of each soft-tissue filler being exam-ined in a study. For example, the selection, mea-surement, and clinical relevance of the outcomes andthe appropriateness of the timing of follow-up in agiven study were evaluated with respect to thecharacteristics and expected duration of the soft-tissue filler(s) being studied.

Similar to the process used by the Effective HealthCare Program, we assigned a summary grading of‘‘good,’’ ‘‘fair,’’ or ‘‘poor,’’ to rate the overall quality ofa study, where the rating of ‘‘good’’ was given to astudy meeting all of the above criteria. Using thismethod, by default, only formal randomized con-trolled trials could receive a grade of ‘‘good.’’However, randomized controlled trials could alsobe downgraded to ‘‘fair’’ or ‘‘poor’’ if they did notmeet all of the criteria. The highest rating attainableby observational (nonexperimental retrospective orprospective) studies was ‘‘fair.’’ Case series/singlecase reports were all rated ‘‘poor.’’

SUMMARY OF THE EVIDENCEShort- and long-term safety, efficacy, andeffectiveness

All 198 studies (including 97 case series/reports)that we identified in our search investigated and/orreported on the safety (e.g., occurrence of adverseevents), efficacy, or effectiveness of soft-tissue fillers,including 33 studies thatwere randomized controlledtrials. The findings from these studies are organizedbelow by soft-tissue filler and, within each section,are presented by the site of injection. Hyaluronic acidfillers were most often investigated, and nasolabialfolds were the most commonly injected areas.

Hyaluronic acid fillersOur search returned 83 studies evaluating the

efficacy and/or safety of hyaluronic acid fillers,including 25 randomized controlled trials, 13 uncon-trolled clinical trials, four cohort studies, one cross-sectional study, and one systematic review. Inaddition, we identified 39 case series/reports thatdiscussed adverse events in patients treated withhyaluronic acid fillers. The various hyaluronic acidfillers that were investigated in the literature, and the

Table V. Distribution of reported commercialhyaluronic acid fillers by study design

HA filler RCTs Other study designs

Restylane 15 12Juv�ederm 12 1Hylaform 5 0Perlane 4 2Captique 2 0Puragen 2 0Teosyal 0 1

HA, Hyaluronic acid; RCTs, randomized controlled trials.

Table IV. Evidence grading criteria

RCT (i.e., comparative study design with least risk of bias)Clear description of the following:PopulationSetting of careInterventionsComparison groupsOutcomes

Duration/timing of follow-upStatistical/analytical methodsNo obvious reporting errorsLow dropout rateClear reporting of dropouts

RCT, Randomized controlled trial.

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number of randomized controlled trials and otherstudy designs (excluding case reports and caseseries) we identified per hyaluronic acid filler, arelisted in Table V. Restylane appeared most often inthe relevant studies that were captured. Follow-upperiods ranged from 3 to 12 months, with fewer thanhalf of the studies (43 percent) conducting follow-uppast 6 months.

Of the 25 randomized controlled trials that exam-ined the hyaluronic acid fillers, 20 assessed the use ofa hyaluronic acid filler injected exclusively into thenasolabial fold area. The remaining clinical trials andother study designs examined injection at other sites,including lips, glabellar lines, marionette lines, arm,hand, cheek, chin, and/or unspecified sites. Thefollowing sections describe relevant studies by thesite of injection.

Nasolabial folds. The majority of the studiesfocused on hyaluronic acid treatment in the nasola-bial folds were randomized controlled trials (n = 20)and compared the use of a hyaluronic acid filler withanother filler. Of these, hyaluronic acid was com-pared with collagen (seven studies) and calciumhydroxylapatite (two studies), whereas 11 studiescompared two hyaluronic acid fillers. Of the 11studies comparing two hyaluronic acid fillers, com-parisons were conducted in a variety of ways: onehyaluronic acid filler versus another hyaluronic acidfiller (seven studies), one concentration of a hyalur-onic acid filler versus a different concentration of thesame filler (one study), the same hyaluronic acidfiller with and without the incorporation of lidocaine(two studies), and the same hyaluronic acid fillerwhile the time point at which subjects receivedretreatment was varied (one study). In addition tothese randomized controlled trials, three uncon-trolled clinical trials examined hyaluronic acid usefor nasolabial fold exclusively.

In general, among the seven randomized con-trolled trials comparing hyaluronic acid with

collagen, hyaluronic acid was equal or superior tocollagen in correcting nasolabial folds, and theadverse events tended to occur early, were minor,and resolved soon after injection. Two of theserandomized controlled trials compared the hyalur-onic acid filler Juv�ederm (Allergan, Inc., Irvine,Calif.) to the bovine collagen filler Zyplast (InamedCorp., Santa Barbara, Calif.). In one of these studies,a double-masked randomized controlled trial con-ducted in the United States (n = 439), subjects wererandomized to receive one of three smooth-gelJuv�ederm fillers (Juv�ederm 30, Juv�ederm Ultra, andJuv�ederm Ultra Plus) intradermally to the nasolabialfold on one side of the face. Each subject thenreceived cross-linked Zyplast in the nasolabial foldon the other side of the face. In comparison toZyplast, the study found that the three Juv�ederm soft-tissue fillers provided a longer lasting correction,measured by the mean level of improvement innasolabial fold severity using the five-point WrinkleAssessment Scale. At 24 weeks, the mean level ofimprovement (i.e., a reduction in points using theWrinkle Assessment Scale) from baseline was greaterthan or equal to one point with the Juv�ederm fillersand less than or equal to a half point with the Zyplastcomparison. The trial also found that all fillers weresimilarly well tolerated by patients.3

Similarly, in a double-blind, within-subject, ran-domized controlled trial (n = 87) comparingJuv�ederm Ultra Plus treatment with Zyplast, themean correction after treatment (using the static,validated Wrinkle Assessment Scale) was compara-ble for both products. However, over the 24-weekfollow-up period, scores for Zyplast nearly returnedto baseline, whereas the Juv�ederm Ultra Plus scoresmarking improvement remained. Subjects wereallowed to receive a repeated treatment with thehyaluronic acid filler at the 24-week follow-up visit.The study found that 88 percent of the severenasolabial folds treated still had clinically significantcorrection at 1 year after retreatment, which requireda significantly lower injection volume (0.6 ml

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compared with 1.7 ml). Occurrence of treatment-siteadverse reactions was similar for both soft-tissuefillers investigated in this study. The majority of theindividual reactions reported lasted no more than 7days, were mild or moderate in severity, and re-quired no further intervention. Examples includederythema, induration, pain, edema, nodules, bruis-ing, pruritus, and discoloration.4

Another two randomized controlled trials com-pared the hyaluronic acid filler Restylane (Q-MedEsthetics, Uppsala, Sweden) with a collagen filler.One of these randomized controlled trials, a double-blind, within-subject, randomized controlled trial(n = 138) conducted in 2003 compared Restylanewith Zyplast, with outcomes assessed at 2, 4, and 6months after injection into contralateral nasolabialfolds. The study concluded that Restylane providedmore durable aesthetic improvement than collagen,as indicated by Wrinkle Severity Rating Scale(p \ 0.0001) and Global Aesthetic ImprovementScale (p\ 0.0001) evaluation. The study noted thatthe frequency, intensity, and duration of localinjection-site reactions were similar for the two fillertypes. Furthermore, the study found that mild ormoderate delayed-onset reactions (defined by thestudy as reaction occurring 14 days or more aftertreatment) occurred in 12 patients and with equalfrequency at hyaluronic acide and collagen-treatedsites. Of these reactions, redness was the most com-mon, and all were mild or moderate in intensity andresolved within 2 to 3 months without treatment.5

A multicenter, within-subject, randomizedcontrolled trial (n = 149) conducted in 2007 comp-ared treatment with Restylane and porcine collagen-derived Dermicol-P35 (Evolence; ColBar LifeScienceLtd., Herzliya, Israel). Based on a 6-month follow-upevaluation and Modified Fitzpatrick Wrinkle Scaleassessments, 97.3 percent of subjects injected withEvolence saw a half-point improvement in theirModified Fitzpatrick Wrinkle Scale assessment, com-pared with 98 percent of subjects injected withRestylane. The study concluded that the effectivenessof Evolence is maintained for at least 6 months and isequivalent to hyaluronic acid for the correction ofnasolabial folds. The majority of injection-site reac-tions were of 4 days’ duration or less, with almost allresolving within 1 week. Erythema was the mostcommonly reported reaction.6

The two studies comparing hyaluronic acid andcalcium hydroxylapatite, also known as Radiesse(BioForm Medical, Inc., San Mateo, Calif.), weremulticenter, blinded, split-face, randomized con-trolled trials conducted in Europe by the sameinvestigators, and determined that calcium hydrox-ylapatite was superior to hyaluronic acid fillers in the

treatment of nasolabial folds. One of these studies(n = 205) compared three hyaluronic acid fillers[Juv�ederm 24, Juv�ederm 24HV, and Perlane (Q-MedEsthetics)] with calcium hydroxylapatite, with out-comes assessed at 4, 8, and 12 months. Investigatoranalysis using the Global Aesthetic ImprovementScale found that calcium hydroxylapatite showed thelargest number of nasolabial folds rated ‘‘improved’’or better. This was statistically significant comparedwith all hyaluronic acid fillers and all time pointsexcept one (at 12 months compared with Juv�ederm24HV, p # 0.05 ), and led the authors to concludethat the calcium hydroxylapatite was more effectiveand longer lasting than each hyaluronic acid filler inmaintaining nasolabial fold augmentation. With re-spect to safety, no serious adverse events requiringintervention were required at any time points for anyof the injected materials.7 The other study (n = 60) bythe same investigators compared Restylane andcalcium hydroxylapatite with outcomes assessed at6, 9, and 12 months. Calcium hydroxylapatite wasfound to be significantly more effective than hyalur-onic acid, showing greater improvement and longerlasting effects, as evidenced by blinded evaluatorWrinkle Severity Rating Scale ratings that showed amean improvement at 12 months of 0.41 for calciumhydroxylapatite and 0.14 for hyaluronic acid (p =0.007). Both products were well tolerated, and noserious adverse events were reported with eithertreatment. Only four adverse events (two hemato-mas, one nodule, and one extrusion) were reportedin 118 folds injected two times each during thecourse of treatment and were resolved withoutcomplications.8

The majority of randomized controlled trials thatexamined the use of hyaluronic acid fillers fornasolabial folds (n = 11 studies) compared twodifferent hyaluronic acid fillers. For example, adouble-blind, randomized controlled trial (n = 150)conducted in Canada in 2005 compared treatmentwith Perlane and Hylaform (Inamed), with eachpatient receiving contralateral injections of each fillerinto the mid or deep dermis nasolabial folds. Thestudy found that Perlane provides a superior im-provement compared with Hylaform, as indicated byWrinkle Severity Rating Scale and Global AestheticImprovement Scale assessments at 6 months show-ing greater and longer lasting improvement. Usingthe Wrinkle Severity Rating Scale, 75 percent ofpatients receiving Perlane treatment had a greaterthan one grade improvement at 6 months, andevaluators rated 64 percent of patients’ correctionssuperior to those achieved with Hylaform. Forpatients treated with Hylaform, 38 percent had agreater than one grade improvement in Wrinkle

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Severity Rating Scale score, and evaluators rated 8percent as superior. Adverse events occurred morefrequently with use of Perlane than with Hylaform(41.3 percent compared with 21.3 percent) but werelimited to common reactions such as swelling, pain,and redness, and the study concluded that this wasan acceptable tolerability profile.9

A more recent randomized controlled trial, con-ducted in 2009 (n = 84), compared the newerhyaluronic acid filler Puragen (Mentor Corp., SantaBarbara, Calif.) and Captique (Inamed), and carriedout follow-up evaluations at 2, 4, and 6months. Usingthe Wrinkle Severity Rating Scale, Puragen wasassessed to be superior to Captique at all follow-uptime points (p \ 0.05). At 6 months after baseline,Puragen was superior to Captique in 60.4 percent ofcases, andCaptiqueproved superior to Puragen in 5.8percent of cases (p \ 0.05). In terms of the GlobalAesthetic Improvement Scale evaluation, Puragenwas also rated significantly higher compared withCaptique at all follow-up time points (p\ 0.05) At 6months after baseline, Puragen was superior toCaptique in 75 percent of patients, and Captiquewas superior to Puragen in 5.8 percent (p \ 0.05).Efficacy assessments by patients gave resultsequivalent to those of the investigator. During thefollow-up period, adverse reactions were observedexclusively at the injection site in 14.7 percent ofPuragen patients and 11.8 percent of Captique pa-tients. Furthermore, delayed-onset complications(defined in the study as arising 14 days after the lasttreatment) had a similar incidence between the twoproducts and subsided spontaneously within 2months after treatment. The study concluded thatboth products are equally effective and safe in elim-inating nasolabial folds, although treatment withPuragenobtainedmore long-lasting and stable resultsin subjects.10

Among the three uncontrolled clinical trials as-sessing the use of hyaluronic acid fillers for nasola-bial folds, we identified a study (n = 18) conducted inCanada that focused on the use of Perlane to treatnasolabial folds in human immunodeficiency virusepositive men with facial lipoatrophy. Facialassessment was conducted at 1 and 12 months usingphotographic evaluation on a seven-point Likertscale. During the study, patients did not regress totheir preinjection levels of lipoatrophy. At the 12-month interval, there was still a slight significantdifference in facial assessment from the preinjectionscores (p = 0.0466). Furthermore, no significantdifference in Likert scale grade was shown betweenthe 1- and 12-month photographs (p = 0.3693),indicating that the patients did not regress to theirpreinjection levels of lipoatrophy. The investigators

concluded that Perlane is a feasible option forcorrection of facial lipoatrophy, and the procedurewas well tolerated without any long-term adverseevents observed.11

Other sites. From our review, a total of 17studies investigated hyaluronic acid filler injectionat specific sites other than or in combination withnasolabial folds, including three randomized con-trolled trials, 12 uncontrolled clinical trials, and twocohort studies. Restylane was used as a hyaluronicacid filler for treatment in all of the studies describedbelow by respective injection site.

For example, a prospective, blinded, randomizedcontrolled trial (n = 283) conducted in 2008 in theUnited States compared the use of two hyaluronicacid fillers, Restylane and Perlane, for midface vol-ume correction of nasolabial folds and marionettelines. Injection occurred at a total of 1021 sites acrossthe patient population, and touch-up injections werediscouraged to parallel clinical practice. Patientswere followed for 12 weeks for adverse eventsonly. A total of 336 local injection-related eventswere reported at 12 weeks, including bruising,tenderness, edema, and pain. Furthermore, the inci-dence of local adverse events was higher at 72 hoursafter injection compared with 2 weeks. The prelim-inary logistic regression demonstrated that injectiontechnique variables strongly influenced the rate oflocal adverse events, including injection type, fanlikeinjection technique, injection volume, and correctiontime. It was also determined that other variables,such as the product injected, injection site, andinjection depth were not found to be correlatedwith the rate of local adverse events. The authorsconcluded that local adverse events following injec-tion with the hyaluronic acid gel fillers used wererelated to investigator technique and not intrinsicdifferences between the hyaluronic acid filler prop-erties, which suggested that moderating the rate ofinjection of hyaluronic acid fillers may lessen theonset of local adverse events.12

Two much smaller randomized controlled trialscompared Restylane to another hyaluronic acid fillerbut at different sites of injection and with differentresults. One randomized controlled trial (n = 10)conducted in Japan compared Restylane andPuragen in the treatment of glabellar lines.Evaluator-blinded assessments at 12 months deter-mined that Puragen was considered superior in 70percent of patients and Restylane was consideredsuperior in 10 percent of patients, although nodifference was seen in the remaining 20 percent.Adverse events were not reported, and the studyconcluded that both Restylane and Puragen areeffective in producing an optimal cosmetic result,

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whereas Puragen provides a more durable aestheticimprovement in the treatment of glabellar lines.13

Restylane was compared with the collagen fillerCosmoplast (Inamed) for the treatment of femalepatients experiencing dermal thinning of the dorsalhands in a double-blind, within-subject, random-ized controlled trial (n = 10) conducted in 2008 inCanada. Follow-up assessment was conducted at 6months by two blinded physicians using a scale of1 to 5 to rate the general clearance of rhytides,veins, bony prominence, and dermal and subcuta-neous atrophy. In addition, patients assessed toler-ability and satisfaction on scales ranging from 1 to5, and the resulting scores indicated that Restylanewas superior to collagen regarding duration andadministration. Reported adverse events includedpain, tingling, and bruising, and one patientexperienced nodule formation at the collagen in-jection site, which resolved itself by the 6-monthfollow-up.14

Restylane was also studied in an uncontrolledclinical trial (n = 154), conducted in 2005 in Canada,to treat the lips of women with prominent down-turned mouth corners. Evaluation was conducted bythe treating investigator at 3, 4.5, and 6months, usinga set of standardized criteria indicating the amount ofimprovement obtained by the patient (i.e., none,slight, moderate, or superb). Evaluation at 4.5months showed that 60 percent of subjects had amoderate or slight improvement and that, at 6months, 50 percent retained a slight improvement,whereas the remaining 50 percent returned to base-line. Adverse events such as pain, redness, swelling,lumping, superficial aggregate of material, and can-ker sore were reported following injection but wereexpected and transient. Three subjects reportedpostinjection herpes labialis that was treated for 7days. The investigators concluded that hyaluronicacid injection to improve age-related changes in thelateral lip corners was effective, safe, and welltolerated in this small prospective study. It was alsonoted that the persistence of correction at 3, 4.5, andin some cases up to 6 months was longer than theyhad experienced with other temporary biodegrada-ble soft-tissue fillers.15

In another, smaller uncontrolled clinical trial (n =60), patients seeking chin and/or cheek augmenta-tion were treated with Restylane SubQ. Injectionswere performed in 98 cheeks and 16 chins, with 12patients receiving touch-up injections at 20 sites(cheek, n = 13; chin, n = 7). Follow-up was carriedout at 1, 3, 6, 9, and 12 months using GlobalAesthetic Improvement Scale assessment performedby patients and investigators. Patients reported anaesthetic improvement (i.e., somewhat, moderately,

or very much improved) at the treatment site(s) in91 percent of cases at 6 months and 58 percent ofcases at 12 months. Investigators considered treat-ment to be effective in 96 percent of cases at 6months and 52 percent of cases at 12 months.Reported adverse events occurred in 58 percent ofpatients and were treatment-related at the injectionsite, including swelling, tenderness, redness, bruis-ing, pain, and pruritus. The majority of adverseevents (70 percent) occurred on the day of treat-ment or on the following day. Skin induration wasfrequently a delayed-onset adverse event and per-sisted for 4 months on average. The study con-cluded that Restylane is well tolerated and providesrelatively long-lasting aesthetic correction of thecheeks and chin.16

Among the cohort studies that examined hyalur-onic acid filler use in other injection sites, a morerecent prospective, open noncomparative study(n = 16) investigated treatment of mild to moderatebrachial ptosis in women. Subjects were treated withRestylane Vital in the arm with three sessions at 30-day intervals. Statistically significant increases at 90days were measured for skin hydration, thickness,and gross elasticity, indicating that hyaluronic acidtreatment can improve the biophysical propertiesand appearance of the skin. No unexpected orserious adverse events were reported, and all ex-pected treatment-related adverse events includingdiscomfort at the injection site, bruising, and hema-toma were of mild intensity.17

Collagen fillersOur search returned 34 studies evaluating the

efficacy and/or safety of collagen fillers, including 13randomized controlled trials, two controlled clinicaltrials, one uncontrolled clinical trial, one cohortstudy, and 17 case series/reports. Among the 17studies (excluding case series/reports), nine ran-domized controlled trials assessed the use of colla-gen injected exclusively into the nasolabial fold area,and the one cohort study assessed its use in thenasolabial fold and other facial wrinkles, includingradial upper lip lines and marionette lines. Theremaining seven studies examined the use of colla-gen in other sites, including the postauricular area(three studies), lip (two studies), arm (one study),and hand (one study). Studies are described by thesite of injection below.

Nasolabial fold and other wrinkles. All 10studies (nine randomized controlled trials) on colla-gen treatments in the nasolabial fold and other facialwrinkles compared the use of a collagen filler withanother filler. The majority of these studies com-pared collagen with another type of filler, including

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hyaluronic acid fillers (six studies), polymethylme-thacrylate (two studies), and calcium hydroxylapa-tite (one study), whereas one study compared twodifferent collagen fillers.

The majority of studies comparing collagen withhyaluronic acid fillers determined that hyaluronicacid fillers were superior to collagen in correctingwrinkles. For example, two randomized controlledtrials described previously demonstrated thatJuv�ederm produced better results than Zyplast asmeasured by the nasolabial fold severity score.3 Oneof these randomized controlled trials (n = 138)concluded that Restylane demonstrated significantsuperiority compared with collagen at 2, 4, and 6months after treatment, as indicated by assessmentsusing the Wrinkle Severity Rating Scale (p\ 0.0001)and the Global Aesthetic Improvement Scale(p \ 0.0001). The study noted that the frequency,intensity, and duration of local injection-site reac-tions were similar for the two types of fillers. Inaddition, the study found that mild or moderatedelayed-onset reactions (defined by the study asreactions occurring 14 days or more after treatment)occurred in 12 patients with equal frequency athyaluronic acide and collagen-treated sites. Of thesereactions, redness was the most common, and allwere mild or moderate in intensity and resolvedwithin 2 to 3 months without treatment.5

The three studies that compared a collagen fillerto polymethylmethacrylate were related studies thatinvestigated polymethylmethacrylate (Artefill; ArtesMedical, Inc., San Diego, Calif.), using Zyderm II(Inamed) or Zyplast as a control, to compare thecosmetic correction of nasolabial folds as a result ofusing each filler and to explore the safety of poly-methylmethacrylate.18-20 These studies are describedlater in the section on polymethylmethacrylate.

Of the remaining studies that examined collagentreatment of nasolabial folds and other wrinkles, onerandomized controlled trial (n = 117) enrolled sub-jects with moderate to deep nasolabial folds whowere randomized to receive calcium hydroxylapatiteon the nasolabial fold on one side of the face andhuman collagen (Cosmoplast) on the other side. Thestudy found that 79 percent of subjects had superiorimprovement at the calcium hydroxylapatiteeinjected site through 6 months (p \ 0.0001). Thestudy reported that adverse event rates were com-parable for both treatments; however, there wassome increase in bruising and edema at the calciumhydroxylapatiteeinjected site. Adverse event dura-tion was similar for both treatments and resolvedwithin 14 to 21 days.21

The remaining randomized controlled trial(n = 12) compared the efficacy and safety of

Evolence30, a porcine-derived collagen gel basedon Glymatrix (ColBar LifeScience) cross-linkingtechnology, with Zyplast, a bovine cross-linkedcollagen. Assessed using the Modified FitzpatrickWrinkle Scale, the two fillers initially improvedwrinkle severity of the nasolabial fold to a similarextent; however, after an average follow-up of 18months, Evolence30 demonstrated superior resultsin nine subjects (p = 0.022). No treatment-relatedadverse events were reported, although transienterythema was observed in both treated sides.22

Lip. We identified two studies that investigatedthe use of collagen fillers in the lip, including onerandomized controlled trial and one cohort study.The randomized controlled trial (n = 44) randomlyassigned patients with age-related changes in thesize and contour of the upper lip to Zyplast or aninjectable acellular dermal graft (Cymetra; LifeCellCorp., Branchburg, N.J.). Using a number of mea-surements, it was concluded that Cymetra-treatedpatients experienced a greater increase in upper lipbulk, vermilion, and lower lip projection. All patientsin the study tolerated treatment well, without anysignificant local or systemic complications.23

A retrospective cohort study examined the safetyand efficacy of Dermicol-P35 30G (Evolence) insubjects who received the injection to restore thecontour of the upper and/or lower lip. Scoresmeasuring investigator assessment, investigator sat-isfaction, and patient satisfaction indicated thatDermicol-P35 30G produced favorable lip enhance-ment results. At the 10-month follow-up, 95 percentof patients experienced no swelling, 100 percentexperienced no bruising, 100 percent experiencedno pain associated with treatment, and 85 percentexperience no lumpiness. When present, lumpinesswas assessed to be very slight or well defined, asopposed to the more serious assessments of moder-ate or severe.24

Other sites. Three studies by Sclafani et al. ex-amined the use of collagen in the postauricular area,including one randomized controlled trial and twocontrolled clinical trials. The randomized controlledtrial (n = 10) evaluated the clinical persistence andhistologic appearance of intradermal Zyplast with asubdermally implanted acellular dermal graft(AlloDerm; LifeCell). Digital photographs of theimplant sites were taken at 1-, 3-, 6-, 9-, and 12-month follow-up visits for assessing the volume ofthe sites. The study found that Zyplast was progres-sively absorbed and lost complete clinical effect by 6months. In contrast, the apparent volume at the siteof the AlloDerm sheets decreased during the first 6months and then stabilized over the next 6 months.25

One of the controlled clinical trials (n = 5) compared

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Zyplast to an autologous collagen dispersion(autologenPlease provide name and city/state loca-tion of manufacturer of Autologen, per Journal stylefor use of brand names.), whereas the other (n = 20)compared Zyplast to a homologous collagen disper-sion (Dermalogen; Collagen Matrix Technologies,Inc., Beverly, Mass.). Both studies concluded that therespective collagen dispersion was a viable alterna-tive to Zyplast based on clinical observations andhistologic findings.26,27

An uncontrolled clinical trial (n = 530), conductedin the United States, also focused on the use ofEvolence. In this study, the potential of Evolence toelicit allergic reactions was examined. Enrolled sub-jects received an intradermal injection of Evolence inthe left forearm and a second injection in the rightforearm after 2 weeks. Injection sites were assessedclinically at 30 minutes and 72 hours after eachinjection and at 30 days after the second injection.Serum anticollagen antibody analyses were alsoperformed before treatment and at the end of thestudy. After treatment, no significant erythematousreactions of positive hypersensitivity were observedin subjects. In addition, most subjects did not displayantibodies against porcine type 1 collagen, and thosewho did showed no change in antibody levels duringthe study, indicating that the injection of the filler didnot result in an immune response by the body. Theinvestigators concluded that the Evolence implantappears to have a low potential for hypersensitivity,and as a result, intradermal skin testing before its useseems to be unnecessary.

As described previously, the injection of thehyaluronic acid filler Restylane was compared withthe collagen filler Cosmoplast for the treatment offemale patients experiencing dermal thinning of thedorsal hands in a small randomized controlled trial(n = 10) conducted in Canada. Follow-up assessmentwas conducted at 6 months by two blinded physi-cians using a scale of 1 to 5 to rate the generalclearance of rhytides, veins, bony prominence, anddermal and subcutaneous atrophy. In addition, pa-tients assessed tolerability and satisfaction on scalesranging from 1 to 5, and the resulting scores indi-cated that hyaluronic acid was superior to collagenregarding duration and administration. Reportedadverse events included pain, tingling, and bruising,and one patient experienced a nodule formation atthe collagen injection site, which resolved itself bythe 6-month follow-up.14

Calcium hydroxylapatiteOur search identified 32 studies on the use of

calcium hydroxylapatite (Radiesse), including threerandomized controlled trials, 15 uncontrolled clinical

trials, two cohort studies, one cross-sectional study,and 11 case series/reports. The most frequentlystudied site across these studies was the nasolabialfolds, followed by the cheeks.

Nasolabial folds and other facialwrinkles. The three randomized controlled trialsthat examined the use of calcium hydroxylapatitewere all conducted in patients with moderate tosevere nasolabial folds. The largest randomizedcontrolled trial (n = 205) treated patients with eithercalcium hydroxylapatite or one of three hyaluronicacid fillers (Juvederm 24, Juvederm 24HV, orPerlane) for the correction of nasolabial folds. Thestudy evaluated efficacy outcomes using GlobalAesthetic Improvement Scale and Wrinkle SeverityRating Scale scores and patient satisfaction using asurvey. At 8 months, Global Aesthetic ImprovementScale scores indicated that significantly more cal-cium hydroxylapatiteetreated nasolabial folds wereimproved compared with the hyaluronic acide-treated nasolabial folds. Mean change in WrinkleSeverity Rating Scale scores from baseline, however,showed no statistically significant difference be-tween the products. Calcium hydroxylapatite wasrated the highest on all four yes/no survey questionson patient satisfaction. No serious adverse eventswere reported at any time during the study.7

Another randomized controlled trial (n = 60) com-pared the use of calcium hydroxylapatite withRestylane and found that at 6-, 9-, and 12-monthfollow-up, calcium hydroxylapatite was significantlymore effective than hyaluronic acid in correctingnasolabial folds based on blinded Global AestheticImprovement Scale and Wrinkle Severity RatingScale ratings. Both products were considered safeand well tolerated.8 The third randomized con-trolled trial (n = 117) compared calcium hydroxyl-apatite with human-based collagen (Cosmoplast)for 6 months. An evaluation of subject photographsby blinded experts indicated that calcium hydrox-ylapatite achieved superior improvement comparedwith collagen (p\ 0.0001). Adverse event rates forboth treatments were comparable, with some in-crease in bruising and edema at calcium hydrox-ylapatiteetreated sites.21

In addition to the three randomized controlledtrials, 10 other studies assessed the use of calciumhydroxylapatite for the correction of nasolabialfolds, including eight uncontrolled clinical trials,one cohort study, and one cross-sectional study.Overall, these studies indicated that calcium hy-droxylapatite was effective and well tolerated inpatients for treating nasolabial folds. For example,the cohort study (n = 1000), which followed patientsfor 52 months, found that calcium hydroxylapatite

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performed well and resulted in a favorable safetyprofile, high patient satisfaction, and good durabil-ity.28 A recently published uncontrolled clinical trial(n = 100) assessed 6-month safety results of calciumhydroxylapatite for the treatment of nasolabial foldsin Fitzpatrick skin types IV to VI. Results from thisstudy indicated that study subjects with dark skininjected subdermally with calcium hydroxylapatitedid not show signs of keloid formation, hypertro-phic scarring, hyperpigmentation or hypopigmen-tation, or other clinically significant adverseevents.29

Although most of the calcium hydroxylapatitestudies examined patient outcomes, one clinical trial(n = 58) used radiography and computed tomo-graphic scans to assess whether calcium hydroxyl-apatite poses radiographic safety concerns. Thestudy determined that calcium hydroxylapatite isusually visible and does not obscure underlyingstructures on computed tomographic scans. In addi-tion, the study found no evidence that calciumhydroxylapatite migrates or that osteogenesis resultsfrom the calcium hydroxylapatite being placed in thedeep dermis and subcutaneous plane.30

Cheeks. We identified five uncontrolled clinicaltrials that examined the effect of calcium hydroxyl-apatite in the cheek area, all of which reportedimproved cosmetic outcomes and minimal adverseevents. One of these studies (n = 100) was conductedin patients with human immunodeficiency viruseassociated lipoatrophy. The 18-month open-labelclinical trial enrolled 94 men and six women whoreceived calcium hydroxylapatite injections into thesubmalar region. All patients were rated as improvedor better on the Global Aesthetic Improvement Scaleat every time point through 12 months; 91 percentwere rated as improved or better at 18 months. Inaddition, skin thickness measurements were statisti-cally improved at 12 months compared with base-line. Adverse events resulting from the treatmentwere mild (e.g., ecchymosis, edema, erythema, pain,pruritus) and of short duration.31

The other four clinical trials were performed inhealthy patients seeking a fuller appearance to thecheeks. For example, one study (n = 19) treatedwomen with signs of midface volume loss byinjecting calcium hydroxylapatite into the subder-mal and subcutaneous planes of the malar area. At 6months, physician-assessed Global AestheticImprovement Scale ratings indicated that 15 of theremaining 16 subjects were improved, much im-proved, or very much improved. Patient-assessedGlobal Aesthetic Improvement Scale ratings weresimilar, with 14 patients reporting their appearancewas improved, much improved, or very much

improved. Adverse events were reported in twopatients; one reported mild edema and hematoma,and another reported mild ecchymosis andedema.32

Poly-l-lactic acidA total of 33 studies examined outcomes follow-

ing poly-l-lactic acid soft-tissue filler (Sculptra;Sanofi-Aventis, Bridgewater, N.J.) treatment, includ-ing one systematic review, two randomized con-trolled trials, four uncontrolled clinical trials, sevencohort studies, and 19 case series/reports. Of the 14studies (excluding case series/reports), seven studiesevaluated the filler’s use in cheeks only; two studiesevaluated its use in cheeks and other sites (e.g.,temples, infraorbital groove, perioral region, perior-bital region); and the remaining five studies focusedon injection sites including facial scars, nasolabialfold, neck and chest, and hand.

Cheeks. One systematic review, two randomizedcontrolled trials, two uncontrolled clinical trials, andtwo cohort studies assessed the use of poly-l-lacticacid in cheeks as the only injection site. Two addi-tional cohort studies reported data on multipleinjection sites that included cheeks. The majority ofthese studies were conducted exclusively in patientswith human immunodeficiency virus (five studies),whereas two studies included both human immuno-deficiency virusepositive and human immunodefi-ciency virusenegative patients. The remaining studyevaluated poly-l-lactic acid for cosmetic use incheeks and other sites.

The systematic review, published in 2006, identi-fied six clinical trials that assessed the intradermalinjection of poly-l-lactic acid for the treatment ofhuman immunodeficiency viruseassociated lipoat-rophy. Based on results from the clinical trials, thereview found that patients who received poly-l-lacticacid had improved cutaneous thickness. In addition,adverse events were mild and tolerable in mostpatients. However, the review noted that all six trialswere conducted primarily in white men and thatfurther research is needed in nonwhite populations.33

The other studies that included patients withhuman immunodeficiency virus similarly supportthe use of poly-l-lactic acid in cheeks. For example,a randomized controlled trial (n = 30) that random-ized subjects to immediate or delayed poly-l-lacticacid treatments found that both treatment groupssustained significant improvements in facial assess-ment using visual analogue scale scores at 18 monthscompared with baseline (immediate, p \ 0.05;delayed, p\0.001). The randomized controlled trialalso determined that patients’ Hospital Anxiety andDepression Scale scores improved for both groups

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following treatment (p \ 0.05). This change wasstatistically significant (p \ 0.05) for Depressionscores in the delayed group. The randomizedcontrolled trial reported one case of injection-siteinduration and nine cases of injection-sitenodules, none of which was described as serious orsevere.34

One retrospective study conducted in the UnitedKingdom (n = 221) evaluated the use of poly-l-lacticacid for cosmetic purposes. Themajority of subjects inthis studywerewomenwho received facial injectionsin a variety of specific sites, including cheeks, chin,perioral region, and periorbital region. The studyobserved that subjects treated with poly-l-lactic acidreported cosmetic improvements that were sustainedfor up to 24 months. The most frequently reportedadverse events were related to injection and resolvedspontaneously within several days with no furthertreatment; however, the study found that treatment tothe perioral and periorbital regions was associatedwith an increased risk of papules or nodules.35

Other sites. Two studies examined the use ofpoly-l-lactic acid in the nasolabial fold. One of thesestudies, published in 2008, was a clinical trialconducted in Brazil that assessed poly-l-lactic acidtreatment in the nasolabial folds of 10 healthywomen for aesthetic reasons. The study concludedthat poly-l-lactic acid was able to correct nasolabialfolds successfully, with results lasting up to 18months for most subjects and up to 36 months forfour subjects. Minor complications (e.g., edema,small hematomas) lasting 2 to 10 days after injectionwere observed in several subjects.36 The other studywas a prospective cohort study from Spain (n = 138)that was limited to human immunodeficiency viruseinfected subjects presenting with antiretroviral-associated facial lipoatrophy. Following subjects for96 weeks, the study compared the effects of poly-l-lactic acid treatment to polyacrylamide gel andautologous fat treatments for correcting sunken naso-labial folds. No serious adverse events were detectedwith any of the treatments. All treatments were deter-mined to be effective based on clinical inspection andfacial photographs of patients for up to 48 weeks.37

One clinical trial conducted in the United States(n = 20) treated patients with poly-l-lactic acid forfacial scars resulting frommoderate to severe acne orvaricella. Results from the trial indicate that poly-l-lactic acid was effective in significantly reducingscar size. Adverse events were limited and notrelated to treatment.38

A retrospective cohort study conducted in theUnited States (n = 26) examined data from threeclinical practices using poly-l-lactic acid to rejuve-nate the aging hand. The study reported that patients

were very satisfied with the results of the treatmentand experienced only minor and short-terminjection-related adverse events.39

As previously described, a retrospective study con-ducted in the United Kingdom (n = 221) found thatnodules occurred in subjects who were treated withpoly-l-lactic acid in the perioral andperiorbital regions.As such, the study recommended that these areas beavoided as sites for poly-l-lactic acid treatment.35

PolymethylmethacrylateOur search returned two randomized controlled

trials and one cohort study on polymethylmethacry-late soft-tissue fillers (Artefill). In addition, weidentified 10 case series/reports pertaining topolymethylmethacrylate.

The two studies that compared polymethylme-thacrylate to a collagen filler were related studies.A 2004 randomized controlled trial (n = 251) inves-tigated polymethylmethacrylate (Artefill), usingZyderm II or Zyplast as a control, to compare thecosmetic correction and explore the safety of poly-methylmethacrylate at 1, 3, 6, and 12 months as aninjectable implant. Nasolabial fold correction wasassessed by masked observers (using photographs)and investigator ratings using the facial fold assess-ment scale. Although there were no statisticallysignificant differences in cosmetic correction be-tween the two fillers after 1 month, polymethylme-thacrylate exhibited significant improvement by the3-month evaluation (masked observers, p \ 0.001for both groups). Polymethylmethacrylate correctioncontinued until the final follow-up at 12 months(p \ 0.001 for both groups). Although adverseevents were uncommon in both groups, redness,swelling, and lumpiness were noted more in thecollagen group. There were a total of 27 adverseevents in the Artefill group compared with 38 in thecollagen-treated group (p = not significant). It wasconcluded that the study demonstrated the safetyand effectiveness of Artefill relative to the collagencontrol for the treatment of nasolabial folds.18

In 2006, the authors published a follow-up studyon a subgroup of patients (n = 69) who receivedpolymethylmethacrylate, recalled 4 to 5 years later.Investigator Facial Fold Assessment Scale ratings at 4or 5 yearswere improved frombaseline by 1.67points(p\ 0.001). With respect to adverse events experi-enced, five patients reported six late adverse events,of 272 wrinkles injected (2.2 percent), that occurredfrom 2 to 5 years after the initial injection. Four werecases of mild lumpiness, and two were severe,including a nodular, minimally inflammatory to non-inflammatory reaction in both nasolabial folds.19

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In 2007, the same investigators published a 5-yearfollow-up study of the polymethylmethacrylate filleretreated cohort that participated in the originalrandomized controlled trial to evaluate the long-term safety and efficacy of the product. Facial foldassessment ratings were performed by blinded ob-servers at 5 years compared with baseline, and thepolymethylmethacrylate filler maintained significantnasolabial fold correction at 5 years compared withbaseline (p \ 0.001). As such, polymethyl-methacrylate is the only U.S. Food and DrugAdministrationeapproved filler with a documenteddurability over a 5-year period. Of the 145 subjectsthat were evaluated for safety, 20 treatment-relatedadverse events were observed among 15 subjects;the most commonly observed was lumpiness, and itwas deemed mild in 80 percent of cases. Thepolymethylmethacrylate filler may offer additionalsafety benefits because of the fact that few repeatedtreatments are needed.20

Level of experience/training and supervisionof staff administering filler

None of the studies from our review directlyevaluated the level of experience or training of staffadministering the filler. In most cases, studies did notindicate who provided the injections. Among thestudies that did specify the staff, most reported that aphysician performed the injection.

A 2007 case series described three adverse reac-tions experienced by patients receiving injections at aclinic administered by a practitioner with no medicaltraining or supervision. Records indicated that theinjections contained silicone oil, but the study indi-cated that this could not be verified subsequent topatients’ adverse reactions. In one case, a womanexperienced headache and vomiting only 30 minutesafter injection. On arrival at an emergency depart-ment, she was found to be experiencing acute renalfailure. Two other cases required emergency depart-ment visits andhospital admissionswith interventionssuch as hemodialysis for up to 5 weeks. An investiga-tion of the facility treating these patients found mul-tiple breaches of standard infection-control practice,and promotional materials on the Internet indicated afamilymedicine practice. The practitioner in questionwas trained as a radiology technician and had admin-istered the soft-tissue filler injections without medicalsupervision. These findings emphasize the risks in-volved with soft-tissue filler injections administeredby practitioners with no medical training, and theimportance of public health officials’ awareness ofadverse events associated with such injections.40

In a 2006 study from Brazil, complications afterpolymethylmethacrylate injection are presented.

A variety of practitioners were responsible foradministering the injections, including certified plas-tic surgeons (n = 16), dermatologists (n = 9),urologists (n = 2), and one nonphysician (i.e., anurse). Despite this discrepancy in level of experi-ence and training, the study does not explicitlyaddress or associate the onset of adverse events withthis. It is concluded that, despite being rare, com-plications caused by polymethylmethacrylate fillerinjection are often difficult to treat and that safetyguidelines should be observed when using the fillerfor augmentation.41

As described previously, a prospective, blinded,randomized controlled trial (n = 283) conducted in2008 in the United States compared the use of twohyaluronic acid fillers, Restylane and Perlane, formidface volume correction of nasolabial folds andmarionette lines. Injectionwas performed at a total of1021 sites across the patient population, and touch-up injections were discouraged, to parallel clinicalpractice. Patients were followed for 12 weeks foradverse events only. A total of 336 local injection-related events were reported at 12 weeks, includingbruising, tenderness, edema, and pain. Furthermore,the incidence of local adverse events was higher at72 hours after injection compared with 2 weeks. Thepreliminary logistic regression demonstrated thatinjection technique variables strongly influencedthe rate of local adverse events, including injectiontype, fanlike injection technique, injection volume,and correction time. It was also determined thatother variables, such as the product injected, injec-tion site, and injection depth were not found to becorrelated with the rate of local adverse events. Theauthors concluded that local adverse events follow-ing injection with the hyaluronic acid gel fillers usedwere related to investigator technique and notintrinsic differences between the hyaluronic acidfiller properties, which suggested that moderatingthe rate of injection of hyaluronic acid fillers maylessen the onset of local adverse events.12

Adverse event reportingRegistries and databases. Registries and data-

bases have been used to collect adverse event dataassociated with injectable soft-tissue filler devices.Although data from these sources cannot be used todraw conclusions between the use of soft-tissuefillers and adverse events, they do provide importantdata that have the potential to identify possibleassociations.

The U.S. Food and Drug Administration maintainsthe Manufacturer and User Facility DeviceExperience database, which represents voluntaryreports of adverse events involving medical devices,

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such as soft-tissue fillers. A recent U.S. Food andDrug Administration analysis of soft-tissue filler de-vices stated that 930 cases of adverse events werereported from January 1, 2003, through September20, 2008. The most frequently reported injection sitewas the nasolabial fold, accounting for 35.6 percentof the reports in which the site of injection wasspecified. However, the majority of reported adverseevents occurred in sites other than the nasolabial fold(e.g., lips, periorbital region, perioral region).1,42

The analysis found that many of the reportedadverse events were mild, such as minor swellingand erythema, and were expected reactions, whichare specified in the product labeling. However,several adverse events were unexpected and seriousin nature, such as facial, lip, and eye palsy; disfig-urement; and retina vascular occlusion. A few rarebut potentially fatal events were reported, such assevere allergic reactions and anaphylactic shock. Inaddition, some of the mild adverse events thatoccurred shortly after treatment had delayed onsetand/or developed into more serious problems. TheU.S. Food and Drug Administration also noted that anumber of reports indicated that the injection wasperformed by untrained personnel or in nonclinicalsettings, which may have contributed to the occur-rence of the adverse event.42

Although the U.S. Food andDrug Administration’sanalysis provides some insight into adverse eventsassociated with soft-tissue fillers, the U.S. Food andDrug Administration noted the limitations of the dataanalysis. For example, a number of reports did notspecify the site of injection (n = 394), and manyreports indicated that a patient received injections atmultiple sites but did not specify which site wasinvolved with the adverse event reported.42

The largest adverse event registry identified by ourreview comprised a database maintained by Q-MedEsthetics, a medical device company that manufac-tures nonanimal stabilized hyaluronic acid fillers(Restylane, Perlane, and Restylane Fine Lines). Thedatabase includes adverse event data from 1999 and2000 that were collected from physicians in Europe,Canada, Australia, South American, and Asia.A retrospective review of these data found thatapproximately 144,000 patients were treated withhyaluronic acid in 1999. During that year, 104 cases ofhypersensitivity, 68 cases of injection-site inflamma-tion, and 30 cases of other adverse events werereported. No systemic symptoms or anaphylaxeswere reported; however, there were rare reports oflocalized granulomatous reactions, bacterial infec-tion, and acneiform and cystic lesions. In 2000, anestimated 262,000 patients were treated, and 52 casesof hypersensitivity, 49 cases of injection-site

inflammation, and 43 cases of other adverse eventswere reported. Two cases of injection-site necrosiswere reported in the glabellar area a few days afterinjection. Rare reports of granulomatous reactions,bacterial infection, and acneiform and cystic lesionswere also reported in 2000. The study concluded thathypersensitivity was the greatest risk associated withhyaluronic acid fillers; however, the study indicatedthat the introduction of a more purified hyaluronicacid material during 1999 appeared to decrease theincidence of hypersensitivity.43

Our review identified two studies reporting datafrom the Berlin-based Injectable Filler Safety registry,a partially population-based registry collecting dataregarding adverse reactions to injectable fillers. Oneof these studies discussed the occurrence of adverseevents following poly-l-lactic acid treatment. Thestudy contacted 583 physicians in private practicesand clinics and achieved a 57.3 percent responserate. Based on the responses by the respondingphysicians, the study identified 22 patients withadverse reactions to poly-l-lactic acid. The mostfrequent adverse event report was nodule formation,which occurred in all 22 patients, followed bypigmentation (n = 8) and inflammation (n = 5). Themean latency between first treatment with poly-l-lactic acid and the first appearance of adverse reac-tion was 6.006 5.84 months. Of the 22 patients withnodule formation, 13 were described as severe. Thestudy noted that the frequency of reported adversereactions to poly-l-lactic acid decreased after 2004,during which the recommended dilution of poly-l-lactic acid was changed from 3 ml to 5 ml. Even withincreased dilution of poly-l-lactic acid, the studyconcluded that adverse events still occur and advisedthat poly-l-lactic acid continue to be monitored forsafety.44

The other study on the Berlin Injectable FillerSafety registry characterized adverse reactions toDermaLive (Dermatech, Paris, France), a fixed com-bination of hydroxyethylmethacrylate and ethylme-thacrylate with hyaluronic acid. The study identified30 patients who were treated with this filler. The mostfrequently treated sites were the nasolabial folds (65percent), followed by glabella and lips. Of the 95treated sites, 87 reported the occurrence of an adversereaction. The most frequently observed adverseevents were the formation of nodules (n = 85),discoloration (n = 39), erythema or inflammation(n = 32), and swelling (n = 24). Most nodular reactionswere rated as severe. The mean time after the lasttreatment to appearance of an adverse reaction was23.1 6 22.8 months, a considerably longer latencyperiod than that observed for poly-l-lactic acid in thestudy described above. Based on the frequency and

Table VI. Distribution of case series/reports bysoft-tissue filler

Soft-tissue filler No. of studies

Collagen 17Hyaluronic acid 39Poly-L-lactic acid 19Calcium hydroxylapatite 11Polymethylmethacrylate 10Other 20

Table VII. Distribution of case series/reports byadverse event reported

Adverse event No. of studies

Allergic reaction 5Swelling 24Inflammatory reaction 20Erythema 18Infection 4Vascular event 2Pain 7Blister/cyst 8Nonspecific mass 15Beading 13Numbness 0Migration 1Biofilm 0Other adverse event 14

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severity of the adverse reactions to DermaLive, theauthors of this study recommended against the use ofthis filler.45

Case series/reportsIn addition to the three studies on adverse

event registries, our review identified 96 case ser-ies/reports presenting a variety of adverse events.Detailed information on adverse events reported inthese case series/reports and other studies can befound in the evidence tables in Appendix B (avail-able at http://www.eblue.org). Table VI shows thebreakdown of these studies by soft-tissue filler type.Of the 96 case studies we identified, the majorityinvolved use of a hyaluronic acid filler.

Table VII below presents the total number of casereports in our review that reported on adverseevents. Among the various types of adverse eventsreported, swelling, inflammatory reactions, anderythema were most often reported.

OUTCOMES IN SUBJECTS WITHFITZPATRICK SKIN TYPES IV THROUGHVI

Among the studies we identified and reviewed,three specifically analyzed the effects of a soft-tissuefiller in patients with Fitzpatrick skin types IVthrough VI. Since 2003, the U.S. Food and DrugAdministration has required postapproval studies ofsoft-tissue fillers in the population with Fitzpatrickskin types IV through VI, a group that was under-represented in premarket clinical studies of soft-tissue fillers. Our search identified a recentlypublished study, which presented results from tworandomized controlled trials that followed subjectswith Fitzpatrick skin phototypes of IV, V, or VI for 24weeks after soft-tissue filler injection into the naso-labial fold. In one of these randomized controlledtrials (n = 160), subjects were randomized to one ofthree high-concentration hyaluronic acid fillers inone nasolabial fold and collagen in the other. In thesecond randomized controlled trial (n = 119),subjects were randomized to receive one of threelow-concentration hyaluronic acid fillers in both

nasolabial folds. The majority of subjects in bothrandomized controlled trials maintained improve-ment in nasolabial fold severity scores through 24weeks. For subjects treated with the high-concentration fillers, there were no occurrences ofhypersensitivity or hypertrophic scarring and noincreased incidence of hyperpigmentation or hypo-pigmentation. For subjects treated with the low-concentration fillers, there were three cases of mildhyperpigmentation and no instances of keloid for-mation, hypertrophic scarring, hypopigmentation,or hypersensitivity. Overall, these findings suggestthat all of the fillers were effective and well toleratedin individuals with skin of color.46

The second study we identified relevant to sub-jects with Fitzpatrick skin types IV through VI alsoreported that a soft-tissue filler was efficacious andsafe in this population. This open-label, nonrandom-ized trial evaluated 100 subjects with Fitzpatrick skintypes IV through VI who received subdermal injec-tions of calcium hydroxylapatite for correcting mod-erate to severe nasolabial folds. For up to 6 monthsafter treatment, there were no signs of keloid forma-tion, hypertrophic scarring, hyperpigmentation orhypopigmentation, or other clinically significantadverse events.29 Similarly, a case series comparinghyaluronic acid treatment in 40 patients withFitzpatrick skin types I through III with 20 patientswith Fitzpatrick skin types IV through VI concludedthat patients with Fitzpatrick skin types IV through VIachieved improved aesthetic outcomes that weresimilar to patients with other skin types. No transientor permanent adverse events were reported amongpatients with Fitzpatrick skin types IV through VI.47

In addition to the three studies described above,five studies included individuals with Fitzpatrick skin

http://www.eblue.org

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types IV through VI in their study sample. Althoughthe five studies do not conduct subgroup analyses inpatients with different skin types, their findings maybe potentially relevant to individuals with Fitzpatrickskin types IV through VI, depending on the extent towhich these individuals are represented in thestudy population. We identified one randomizedcontrolled trial (n = 439) in particular that includeda relatively high percentage of subjects withFitzpatrick skin types IV through VI. This random-ized controlled trial (n = 439) compared the effec-tiveness and safety of hyaluronic acid with collagenfor treating nasolabial folds in subjects of allFitzpatrick skin types (type I, 4 percent; type II, 24percent; type III, 35 percent; type IV, 20 percent; typeV, 13 percent; and type VI, 3 percent). Results fromthis randomized controlled trial were published intwo studies from our review. One of these studiesanalyzed outcomes for all 439 subjects and reportedthat hyaluronic acid soft-tissue fillers offer safer andlonger-lasting clinical correction than collagen. Thestudy did not present the results by skin type;however, it mentioned that the pattern and incidenceof treatment-site reactions were generally similarbetween white and nonwhite subjects.3 The secondstudy examined a set of 87 patients (36 percent withFitzpatrick skin types IV through VI) classified ashaving severe nasolabial folds and similarly con-cluded that hyaluronic acid is a safe and effectivesoft-tissue filler that provides correction for 1 year ormore.4

PREDICTIVE ABILITY AND ACCURACY OFEVALUATION METHODS

In addition to conducting a review of the safety,efficacy, and effectiveness of soft-tissue fillers, wealso searched for studies focused on the predictiveability and accuracy of evaluation methods used forboth approved and off-label use of soft-tissue fillers.Our search identified no directly relevant studies.However, studies identified in our search oftendescribed the specific methods and tools used toassess various outcomes of interest. The followingsection provides an overview of the types of out-comes that were measured in these studies and themethods and tools used to assess these outcomes.None of the methods or tools we came across wasused to predict treatment outcomes resulting fromthe use of soft-tissue fillers.

Efficacy/effectiveness outcomesAcross the literature on soft-tissue fillers, effective-

ness was often determined by the level of aestheticimprovement. Although aesthetic improvement maybe subjective and difficult to quantify, a variety of

evaluation tools have been developed that aim toimprove the validity and reliability of assessments.These tools include ratings of appearance, patientsatisfaction, and treatment success, which were usedin studies evaluating on-label or off-label uses ofsoft-tissue fillers. For studies on facial augmentationfor human immunodeficiency viruseassociated lipo-atrophy, evaluation tools often included methods todetermine skin thickness. Evaluation tools that wereless frequently used included patient questionnaireson quality of life and psychological state and three-dimensional imaging.

Although many studies assessed patient satisfac-tion, very few used validated scales. This finding wasconfirmed by a systematic review on patient-reportedoutcome measures for facial cosmetic surgery andnonsurgical facial rejuvenation. The review found thatvalid, reliable, responsible instruments to measurethese outcomes are lacking. Based on an assessmentof the available literature, the review concluded thatthere is a need to develop patient-reported outcomemeasures designed to measure satisfaction with facialappearance following aesthetic procedures.48

Ratings of appearanceDespite the large variation across the evidence

with regard to soft-tissue filler type, injection tech-nique, injection site, study population, and on-labelversus off-label uses, the majority of studies evaluat-ing aesthetic appearance included the use of avalidated scale, such as the Global AestheticImprovement Scale, the Wrinkle Severity RatingScale, the Facial Fold Assessment scale, theLemperle Rating Scale, the Nasal Fold Severity scale,and the Modified Fitzpatrick Wrinkle Scale. Theevaluation process incorporating these validatedscales varied across the studies we reviewed.Studies differed with regard to the evaluator (e.g.,investigator, physician, expert panel, patient),masked versus unmasked assessment, and liveversus photographic assessment.

Studies that did not use a validated scale to assessaesthetic outcomes tended to examine off-label usesof a soft-tissue filler. For example, one uncontrolledclinical trial on hyaluronic acid treatment for correct-ing downturned mouth corners used a four-pointscale that included ‘‘no difference,’’ ‘‘slight improve-ment,’’ ‘‘moderate improvement,’’ and ‘‘superb im-provement.’’15 One randomized controlled trial (n =44) that treated patients’ lips with bovine collagen(Zyplast) or an injectable acellular dermal graft(Cymetra) assessed lip aesthetics by photographingpatients and using a ruler to measure changes in thenasolabial angle, percentage of the total lip ac-counted for by the exposed red lip in the midline

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and on the lateral view, the visible red upper andlower lip surface areas, and the anterior projection ofthe upper and lower lips.23

Ratings of treatment successSeveral studies used scales to rate treatment suc-

cess; however, all of these scales appeared to benonvalidated. Furthermore, these studies providedvery little detail on how the scales were developed orwhat the criteria were for each score within the scale.For example, the investigators for one randomizedcontrolled trial (n = 119) used a five-point ordinalscale to rate the success of polymethylmethacrylatetreatment. The only description for this scale was alist of the scores, which included ‘‘completely suc-cessful,’’ ‘‘very successful,’’ ‘‘moderately successful,’’‘‘somewhat successful,’’ and ‘‘not at all successful.’’20

Measurements of skin thicknessParticularly in studies focusing on human immu-

nodeficiency viruseassociated lipoatrophy, skinthickness was a frequently assessed outcome mea-sure. None of the methods for determining skinthickness was validated in these studies. The mostfrequently usedmethod for measuring skin thicknessinvolved skin calipers. For example, in an open-labeltrial in which patients received serial injections ofpoly-l-lactic acid, patients were evaluated for in-crease in total cutaneous thickness by skin calipers.The study found that patients had a mean increase inskin thickness of 65.1 percent after treatmentcompared with baseline values.49

Safety outcomesThere was great variation in the level of adverse

event reporting across the studies we reviewed. Mostinterventional and epidemiologic studies (i.e.,nonecase series/reports) simply reported the inci-dence and severity of local and systematic adverseevents. In general, these studies observed few ad-verse events, whichwere transient andmild in natureand the majority of which were associated with theinjection process, such as ecchymosis and erythema.

Several studies reported safety data beyond ad-verse event incidence and descriptions of severity.For example, one open-label trial (n = 25) measuredthe level of cutaneous inflammation after hyaluronicacid injection using an erythema meter and infraredthermometer. These measurements indicated thathyaluronic acid caused some initial inflammation at10 to 20 minutes after injection; however, the inflam-mation decreased substantially by 3 hours.50

Another clinical trial (n = 58) used radiographyand computed tomography to assess whether cal-cium hydroxylapatite poses radiographic safety

concerns. Blinded radiologists determined that cal-cium hydroxylapatite is usually visible and does notobscure underlying structures on computed tomo-graphic scans. In addition, there is no evidence thatcalcium hydroxylapatite migrates or that osteogene-sis results from the calcium hydroxylapatite beingplaced in the deep dermis and subcutaneous plane.30

We identified five studies that characterizedthe immunologic safety profile of a soft-tissuefiller.5-27,51,52 For example, in a study assessingRestylane and Perlane for nasolabial fold correction,Hamilton et al. used skin and serology testing toevaluate humoral immune responses with potentialfor immediate (type I) or immunecomplexemediated(type II and III) hypersensitivity. The study alsogathered histopathologic data using biopsy speci-mens collected from skin test sites to examine subjectsfor possible cell-mediated inflammation that is asso-ciated with delayed (type IV) hypersensitivity. Basedon these evaluations, the study determined thatnoneanimal-stabilized hyaluronic acid does not elicitclinical/laboratory evidence for cellular or humoralimmune responses in 98 percent of individuals,supporting the conclusion that Restylane andPerlane are not commonly immunogenic or aller-genic.51 The other four studies assessed the use ofcollagen as a soft-tissue filler, including one study thatconducted serum anticollagen antibody tests andthree studies that conducted histologic tests. All fourstudies found that the examined collagen filler hadlow potential for immunologic reactions.25-27,52

IMPLICATIONS FOR FUTURE RESEARCHTo inform and support thework of the state-of-the-

science conference panel on soft-tissue fillers, thisreport summarizes and assesses the available litera-ture related to soft-tissuefillers.Our search inPubMedreturned a total of 198 relevant in-scope studies,including four systematic reviews, 33 randomizedcontrolled trials, two controlled clinical trials, 41uncontrolled clinical trials, 18 cohort studies, threecross-sectional studies, and 97 case series or reports.The studies included in this review varied greatlywithregard to study populations, treatment technique(e.g., volume of filler, number of injections, injectionsite), andoutcomesmeasured. Althoughwe classifiedfour studies as systematic reviews, only one of thesestudies documented the methods they used, whereasthe other three studies simply mentioned that aliterature searchwas performed. Among the availableliterature, hyaluronic acid fillers were the most fre-quently discussed filler type (n = 83 studies), followedby collagen (n = 34 studies), poly-l-lactic acid (n = 33studies), calcium hydroxylapatite (n = 32), and poly-methylmethacrylate (n = 13 studies) fillers. A number

Table VIII. Full-text studies reviewed by type ofstudy and quality of evidence grade

Type of study Good Fair Poor

SR 0 0 4RCT 22 9 2CCT 0 1 1UCT 0 0 41Cohort 0 1 17Cross-sectional 0 0 3Case series/case report 0 0 97Total 22 11 165

SR, Systematic review; RCT, randomized controlled trial; CCT,

controlled clinical trial; UCT, uncontrolled clinical trial.

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of studies (n = 36) also addressed other filler typessuch as silicone oil or polyacrylamide gel.

The quality of the studies we captured rangedfrom several well-designed randomized controlledtrials meeting a ‘‘good’’ quality rating to many casereports of single patients, which received a ‘‘poor’’quality rating. Twenty-two of the 33 reviewed ran-domized controlled trials received a ‘‘good’’ qualityrating, whereas only two randomized controlledtrials were graded as ‘‘poor.’’ Thus, the majority ofsoft-tissue filler randomized controlled trials,although not overwhelming in number, werehigh-quality studies. The remaining studies, withoutformal randomization and/or comparison groups,based on the grading system we used, could notreceive a grade higher than ‘‘fair,’’ and only two ofthe studies that were not randomized controlledtrials received a ‘‘fair’’ rating. The 97 case series, withinherent methodologic limitations, were unilaterallymarked as ‘‘poor.’’ Table VIII presents the gradesgiven across the studies we reviewed. Although thegrading was largely based on study design, it shouldbe noted that many of the studies reviewed satisfieda number of other criteria that were included inour evaluation. Evidence tables in AppendixA include the quality grades that were assigned toeach study.

Overall, the evidence indicates that soft-tissuefillers are effective and well tolerated for correctingnasolabial folds, other moderate to severe wrinklesand folds, and volume loss in cheeks. These findingswere observed among patients seeking aestheticfacial rejuvenation and patients with human immu-nodeficiency viruseassociated facial lipoatrophy. Ingeneral, the adverse events in studies focusing onthese treatment sites were mild and transient, such aserythema and ecchymosis, and typically resolvedwithin several days without treatment; however,several studies reported the formation of nodulesin several patients. The reported longevity of soft-

tissue filler effects varied to some extent acrossstudies; however, duration of results generally de-pended on the composition of the filler. The effectsof biological products such as collagen and hyalur-onic acid typically lasted for less than 1 year aftertreatment. Semipermanent fillers, including poly-l-lactic acid and calcium hydroxylapatite, were ob-served to persist for 1 to 2 years in patients.Nonabsorbable fillers such as polymethylmethacry-late, silicone oil, and polyacrylamide gel achievedthe longest lasting aesthetic results, persisting forover 2 years in some studies.

The small number of quality studies examiningother treatment sites (e.g., lips, perioral region,periorbital region) limits the ability to draw firmconclusions regarding the use of soft-tissue fillers inthese areas. Although nearly all patients indicatedhigh levels of satisfaction in studies on other treat-ment sites, these studies tended to have methodo-logic shortcomings, including small sample sizes andthe use of unvalidated evaluation tools. Adverseevents observed were generally minor in othertreatment sites; however, data from one study indi-cated an increased risk of nodules associated withthe use of poly-l-lactic acid treatment in the perioraland periorbital regions.

None of the studies from our review evaluated theimpact of different staff administering soft-tissuefiller treatment or the validity of assessment tools.Our review identified very few studies of patientswith Fitzpatrick skin types IV through VI. The threestudies that specifically assessed outcomes in thesepatients consistently reported favorable efficacy andsafety outcomes following treatment with a soft-tissue filler. Based on our review of the literature,several gaps in the current evidence base wereobserved, including the following key issues.

Need for long-term safety and efficacy dataAlthough the body of evidence we identified

demonstrated that soft-tissue fillers are efficacious,effective, and in general fairly safe, the vast majorityof studies we examined had limited follow-upperiods. Only one study followed patients for5 years.

Need for studies addressing the impact of staffadministering treatment

Soft-tissue fillers are being administered by avariety of practitioners, ranging from trained plasticsurgeons and cosmetic dermatologists to nonclini-cians. Although the training and experience of indi-viduals administering fillers is a growing concern,our review of the literature found no studies thataddressed this issue.

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Development and validation of evaluationtools for assessing effectiveness

Again, our review of the evidence found nodirectly relevant studies that assessed tools to eval-uate the use of soft-tissue fillers. For example,although patient satisfaction following injection ofa soft-tissue filler is often examined, similar to ourfindings, a systematic review of patient-reportedoutcome measures also found valid, reliable instru-ments to measure these outcomes to be lacking. Tothe extent that efforts are made to meet the growinguse and demand for soft-tissue fillers through re-search and development of new and longer lastingfillers, these types of issues should be explored andaddressed to ensure the continued safety, efficacy,and effectiveness of these devices.

The American Academy of Dermatology and theAmerican Society of Plastic Surgeons contracted with TheLewin Group, a health and human services consulting firmlocated in the Washington, D.C., metropolitan area, toprovide analytical support to the conference, including asystematic literature review to inform thework of an expertpanel that was to be established for the conference. TheLewin Group was also contracted to facilitate the expertpanel discussion during the conference and summarize thefindings of the conference in the present report.

REFERENCES

1. U.S. Department of Health and Human Services, U.S. Food and

Drug Administration. Panel Meeting Summary: November 18-

19, 2008 Meeting of the General and Plastic Surgery Devices

Panel. Available at: http://www.fda.gov/cdrh/panel/summary/

gpsd-111808.html. Accessed March 22, 2009.

2. Agency for Healthcare Research and Quality. Methods Refer-

ence Guide for Effectiveness and Comparative Effectiveness

Reviews, Version 1.0 (draft posted October of 2007). Available

at: http://effectivehealthcare.ahrq.gov/repFiles/2007_10Draft

MethodsGuide.pdf. Accessed 2009.

3. Baumann LS, Shamban AT, Lupo MP. Comparison of smooth-

gel hyaluronic acid dermal fillers with cross-linked bovine

collagen: A multicenter, double-masked, randomized, within-

subject study. Dermatol Surg 2007;33(Suppl 2):S128-35.

4. Lupo MP, Smith SR, Thomas JA, Murphy DK, Beddingfield FC

III. Effectiveness of Juv�ederm Ultra Plus dermal filler in the

treatment of severe nasolabial folds. Plast Reconstr Surg 2008;

121:289-97.

5. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A

randomized, double-blind, multicenter comparison of the

efficacy and tolerability of Restylane versus Zyplast for the

correction of nasolabial folds. Dermatol Surg 2003;29:588-95.

6. Narins RS, Brandt FS, Lorenc ZP. A randomized, multicenter

study of the safety and efficacy of Dermicol-P35 and non-

animal-stabilized hyaluronic acid gel for the correction of

nasolabial folds. Dermatol Surg 2007;33(Suppl 2):S213-21.

7. Moers-Carpi M, Vogt S, Santos BM, Planas J, Vallve SR,

Howell DJ. A multicenter, randomized trial comparing

calcium hydroxylapatite to two hyaluronic acids for treat-

ment of nasolabial folds. Dermatol Surg 2007;33(Suppl 2):

S144-51.

8. Moers-Carpi MM, Tufet JO. Calcium hydroxylapatite versus

nonanimal stabilized hyaluronic acid for the correction of

nasolabial folds: A 12-month, multicenter, prospective, random-

ized, controlled, split-face trial. Dermatol Surg 2008;34:210-5.

9. Carruthers A, Carey W, De Lorenzi C, Remington K, Schachter

D, Sapra S. Randomized, double-blind comparison of the

efficacy of two hyaluronic acid derivatives, restylane perlane

and hylaform, in the treatment of nasolabial folds. Dermatol

Surg 2005;31:1591-8.

10. Onesti M, Toscani M, Curinga G, Chiummariello S, Scuderi N.

Assessment of a new hyaluronic acid filler: Double-blind,

randomized, comparative study between Puragen and Cap-

tique in the treatment of nasolabial folds. In Vivo 2009;23:

479-86.

11. Denton AB, Tsaparas Y. Injectable hyaluronic acid for the

correction of HIV-associated facial lipoatrophy. Otolaryngol

Head Neck Surg 2007;136:563-7.

12. Glogau RG, Kane MA. Effect of injection techniques on the rate

of local adverse events in patients implanted with nonanimal

hyaluronic acid gel dermal fillers. Dermatol Surg 2008;34

(Suppl 1):S105-9.

13. Kono T, Kinney BM, Groff WF, Chan HH, Ercocen AR, Nozaki M.

Randomized, evaluator-blind, split-face comparison study of

single cross-linked versus double cross-linked hyaluronic acid

in the treatment of glabellar lines. Dermatol Surg 2008;34

(Suppl 1):S25-30.

14. Man J, Rao J, Goldman M. A double-blind, comparative study

of nonanimal-stabilized hyaluronic acid versus human colla-

gen for tissue augmentation of the dorsal hands. Dermatol

Surg 2008;34:1026-31.

15. Carruthers J, Klein AW, Carruthers A, Glogau RG, Canfield D.

Safety and efficacy of nonanimal stabilized hyaluronic acid for

improvement of mouth corners. Dermatol Surg 2005;31:

276-80.

16. DeLorenzi C,WeinbergM,SolishN, SwiftA. The long-termefficacy

and safety of a subcutaneously injected large-particle stabilized

hyaluronic acid-based gel of nonanimal origin in esthetic facial

contouring. Dermatol Surg 2009;35(Suppl 1):313-21.

17. Distante F, Pagani V, Bonfigli A. Stabilized hyaluronic acid of

non-animal origin for rejuvenating the skin of the upper arm.

Dermatol Surg 2009;35(Suppl 1):389-93; discussion 394.

18. Cohen SR, Holmes RE. Artecoll: A long-lasting injectable

wrinkle filler material. Report of a controlled, randomized,

multicenter clinical trial of 251 subjects. Plast Reconstr Surg

2004;114:964-76; discussion 977-9.

19. Cohen SR, Berner CF, Busso M. ArteFill: A long-lasting inject-

able wrinkle filler material. Summary of the U.S. Food and

Drug Administration trials and a progress report on 4- to 5-

year outcomes. Plast Reconstr Surg 2006;118(3 Suppl):64S-76S.

20. Cohen SR, Berner CF, Busso M. Five-year safety and efficacy of

a novel polymethylmethacrylate aesthetic soft tissue filler for

the correction of nasolabial folds. Dermatol Surg 2007;33

(Suppl 2):S222-30.

21. Smith S, Busso M, McClaren M, Bass LS. A randomized,

bilateral, prospective comparison of calcium hydroxylapatite

microspheres versus human-based collagen for the correction

of nasolabial folds. Dermatol Surg 2007;33(Suppl 2):S112-21.

22. Monstrey SJ, Pitaru S, Hamdi M. A two-stage phase I trial of

Evolence30 collagen for soft-tissue contour correction. Plast

Reconstr Surg 2007;120:303-11.

23. Sclafani AP, Romo T III, Jacono AA. Rejuvenation of the aging

lip with an injectable acellular dermal graft (Cymetra). Arch

Facial Plast Surg 2002;4:252-7.

24. De Boulle BK, Swinberghe S, Engman M, Shoshani D. Lip

augmentation and contour correction with a ribose cross-

http://www.fda.gov/cdrh/panel/summary/gpsd-111808.html

http://www.fda.gov/cdrh/panel/summary/gpsd-111808.html

http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf

http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf

J AM ACAD DERMATOL


linked collagen dermal filler. J Drugs Dermatol 2009;8(3

Suppl):1-8.

25. Sclafani AP, Romo T III, Jacono AA, McCormick SA, Cocker R,

Parker A. Evaluation of acellular dermal graft (AlloDerm) sheet

for soft tissue augmentation: A 1-year follow-up of clinical

observations and histological findings. Arch Facial Plast Surg

2001;3:101-3.

26. Sclafani AP, Romo T III, Parker A, McCormick SA, Cocker R,

Jacono A. Autologous collagen dispersion (autologen) as a

dermal filler: Clinical observations and histologic findings. Arch

Facial Plast Surg 2000;2:48-52.

27. Sclafani AP, Romo T III, Parker A, McCormick SA, Cocker R,

Jacono A. Homologous collagen dispersion (dermalogen) as a

dermal filler: Persistence and histology compared with bovine

collagen. Ann Plast Surg 2002;49:181-8.

28. Tzikas TL. A 52-month summary of results using calcium

hydroxylapatite for facial soft tissue augmentation. Dermatol

Surg 2008;34(Suppl 1):S9-15.

29. Marmur ES, Taylor SC, Grimes PE, Boyd CM, Porter JP, Yoo JY.

Six-month safety results of calcium hydroxylapatite for treat-

ment of nasolabial folds in Fitzpatrick skin types IV to VI.

Dermatol Surg 2009;35(Suppl 2):1641-5.

30. Carruthers A, Liebeskind M, Carruthers J, Forster BB. Radio-

graphic and computed tomographic studies of calcium hy-

droxylapatite for treatment of HIV-associated facial

lipoatrophy and correction of nasolabial folds. Dermatol

Surg 2008;34(Suppl 1):S78-84.

31. Silvers SL, Eviatar JA, Echavez MI, Pappas AL. Prospective, open-

label, 18-month trial of calcium hydroxylapatite (Radiesse) for

facial soft-tissue augmentation in patients with human immu-

nodeficiency virus-associated lipoatrophy: One-year durability.

Plast Reconstr Surg 2006;118(3 Suppl):34S-45S.

32. Beer K, Yohn M, Cohen JL. Evaluation of injectable CaHA for

the treatment of mid-face volume loss. J Drugs Dermatol

2008;7:359-66.

33. El-Beyrouty C, Huang V, Darnold CJ, Clay PG. Poly-L-lactic acid

for facial lipoatrophy in HIV. Ann Pharmacother 2006;40:

1602-6.

34. Moyle GJ, Brown S, Lysakova L, Barton SE. Long-term safety

and efficacy of poly-L-lactic acid in the treatment of HIV-

related facial lipoatrophy. HIV Med 2006;7:181-5.

35. Lowe NJ, Maxwell CA, Lowe P, Shah A, Patnaik R. Injectable

poly-l-lactic acid: 3 years of aesthetic experience. Dermatol

Surg 2009;35(Suppl 1):344-9.

36. Salles AG, Lotierzo PH, Gimenez R, Camargo CP, Ferreira MC.

Evaluation of the poly-L-lactic acid implant for treatment of

the nasolabial fold: 3-year follow-up evaluation. Aesthetic

Plast Surg 2008;32:753-6.

37. Negredo E, Higueras C, Adell X. Reconstructive treatment for

antiretroviral-associated facial lipoatrophy: A prospective

study comparing autologous fat and synthetic substances.

AIDS Patient Care STDS 2006;20:829-37.

38. Beer KA. single-center, open-label study on the use of inject-

able poly-L-lactic acid for the treatment of moderate to severe

scarring from acne or varicella. Dermatol Surg 2007;33(Suppl

2):S159-67.

39. Sadick NS, Anderson D, Werschler WP. Addressing volume loss

in hand rejuvenation: A report of clinical experience. J Cosmet

Laser Ther 2008;10:237-41.

40. Centers for Disease Control and Prevention. Acute renal failure

associated with cosmetic soft-tissue filler injections: North

Carolina, 2007. MMWR Morb Mortal Wkly Rep 2008;57:453-6.

41. Salles AG, Lotierzo PH, Gemperli R. Complications after

polymethylmethacrylate injections: Report of 32 cases. Plast

Reconstr Surg 2008;121:1811-20.

42. Mirsaidi N. Post-Market Evaluation of Adverse Events Reported

to FDA on Dermal Fillers. Washington, DC: U.S. Food and Drug

Administration; 2009.

43. Friedman PM, Mafong EA, Kauvar AN, Geronemus RG. Safety

data of injectable nonanimal stabilized hyaluronic acid gel for

soft tissue augmentation. Dermatol Surg 2002;28:491-4.

44. Rossner F, Rossner M, Hartmann V, Erdmann R, Wiest LG,

Rzany B. Decrease of reported adverse events to injectable

polylactic acid after recommending an increased dilution: 8-

year results from the Injectable Filler Safety study. J Cosmet

Dermatol 2009;8:14-8.

45. Rossner M, Rossner F, Bachmann F, Wiest L, Rzany B. Risk of

severe adverse reactions to an injectable filler based on a fixed

combination of hydroxyethylmethacrylate and ethylmethacry-

late with hyaluronic acid. Dermatol Surg 2009;35(Suppl 1):

367-74.

46. Grimes PE, Thomas JA, Murphy DK. Safety and effectiveness of

hyaluronic acid fillers in skin of color. J Cosmet Dermatol 2009;

8:162-8.

47. Odunze M, Cohn A, Few JW. Restylane and people of color.

Plast Reconstr Surg 2007;120:2011-6.

48. Kosowski TR, McCarthy C, Reavey PL. A systematic review of

patient-reported outcome measures after facial cosmetic

surgery and/or nonsurgical facial rejuvenation. Plast Reconstr

Surg 2009;123:1819-27.

49. Mest DR, Humble G. Safety and efficacy of poly-L-lactic acid

injections in persons with HIV-associated lipoatrophy: The US

experience. Dermatol Surg 2006;32:1336-45.

50. Judodihardjo H, Dykes P. Objective and subjective measure-

ments of cutaneous inflammation after a novel hyaluronic acid

injection. Dermatol Surg 2008;34(Suppl 1):S110-4.

51. Hamilton RG, Strobos J, Adkinson NF Jr. Immunogenicity

studies of cosmetically administered nonanimal-stabilized

hyaluronic acid particles. Dermatol Surg 2007;33(Suppl 2):

S176-85.

52. Shoshani D, Markovitz E, Cohen Y, Heremans A, Goldlust A.

Skin test hypersensitivity study of a cross-linked, porcine

collagen implant for aesthetic surgery. Dermatol Surg 2007;

33(Suppl 2):S152-8.

S85.e1 Hanke et al J Am AcAd dermAtol

April 2011

Ap

pen

dix

A. A

SPS/

AA

D e

vid

ence

tab

les

wit

h o

utc

om

e m

easu

res

and

co

ncl

usi

on

s, lis

tin

g s

tud

ies

by

der

mal

fille

r typ

e an

d s

tud

y ty

pe

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Hya

luro

nic

Aci

d F

iller

sS

yste

mat

ic R

evie

w: N

o. o

f st

ud

ies,

1Pr

ice

et a

l., 2

007

PMID

:174

6661

3Sy

stem

atic

revi

ewU

KN

/AN

/AH

AN

/AD

erm

al fi

ller o

f ch

oic

e fo

r mo

st s

urg

eon

s. In

20

04, a

pp

roxi

mat

ely

45,0

00 t

reat

men

ts w

ere

adm

inis

tere

d b

y A

SPS

mem

ber

su

rgeo

ns.

Incr

ease

d te

n-f

old

by

the

follo

win

g y

ear.

Poo

r

Ran

do

miz

ed C

on

tro

lled

Tri

al: N

o. o

f st

ud

ies,

25

Bau

man

n e

t al

., 20

07PM

ID:1

8086

050

Mu

ltic

ente

r, d

ou

ble

-mas

ked,

ra

nd

om

ized

, w

ith

in-s

ub

ject

st

ud

y

USA

/Su

bje

cts

at le

ast

30 y

r an

d w

ith

fully

vi

sib

le b

ilate

ral

NLF

s th

at w

ere

app

roxi

mat

ely

sym

met

rica

l (b

oth

m

od

erat

e o

r bo

th

seve

re)

439

(423

) 24

wk

HA

: Ju

véd

erm

30

(J30

), Ju

véd

erm

Ult

ra (2

4HV

), Ju

véd

erm

Ult

ra P

lus

(30H

V);

med

ian

, 1.6

ml

(0.8

–5.6

ml)

Sub

ject

s w

ere

ran

do

mly

ass

ign

ed

to re

ceiv

e o

ne

of

the

thre

e sm

oo

th-

gel

HA

fille

rs,

intr

ader

mal

ly to

th

e N

LF o

n o

ne

sid

e o

f th

e fa

ce. I

n a

ll su

bje

cts,

the

NLF

o

n t

he

oth

er s

ide

of

the

face

was

tre

ated

w

ith

Zyp

last

.

All

the

HA

der

mal

fille

rs

resu

lted

in a

mea

n

imp

rove

men

t (i.

e., a

re

du

ctio

n) f

rom

bas

elin

e in

NLF

sev

erit

y sc

ore

, cl

inic

ally

sig

nifi

can

t at

ea

ch t

ime

po

int.

Furt

her

, th

e H

A d

erm

al fi

llers

p

rovi

ded

lon

ger

-las

tin

g

clin

ical

co

rrec

tio

n t

han

b

ovin

e co

llag

en.

Go

od

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l Z

ypla

st (c

ross

-lin

ked

bov

ine

colla

gen

) Va

st m

ajo

rity

of

sub

ject

s h

ad o

nly

o

ne

trea

tmen

t vi

sit.

The

new

sm

oo

th g

el H

A

der

mal

fille

rs w

ere

hig

hly

eff

ecti

ve in

co

rrec

tin

g N

LFs

for

6 m

o o

r lo

ng

er a

fter

tr

eatm

ent.

The

maj

ori

ty

of s

ub

ject

s ac

hie

ved

o

pti

mal

co

rrec

tio

n w

ith

o

nly

a s

ing

le in

ject

ion

o

f th

e H

A d

erm

al fi

ller,

and

th

e fil

lers

wer

e al

so

sim

ilarl

y w

ell t

ole

rate

d.

An

ove

rwh

elm

ing

m

ajo

rity

of s

ub

ject

s ex

pre

ssed

a p

refe

ren

ce

for t

he

smo

oth

gel

HA

d

erm

al fi

llers

ove

r bov

ine

colla

gen

.

Hanke et al S85.e2J Am AcAd dermAtol

Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Bee

r, 20

07

PMID

:176

6193

5 D

ou

ble

-blin

d R

CT

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l

US/

Wo

men

15

(15)

2

wk,

3, 4

.5, a

nd

6

mo

R

esty

lan

e (H

A g

el),

0.7–

2.1

ml

Hyl

afo

rm P

lus

(hyl

an B

plu

s),

0.7–

2.2

ml

A p

hys

icia

n o

r nu

rse

adm

inis

tere

d a

ra

nd

om

ly a

ssig

ned

tr

eatm

ent

to

on

e si

de

of e

ach

p

atie

nt’s

nas

ola

bia

l fo

ld a

nd

th

e o

ther

tr

eatm

ent

to t

he

nas

ola

bia

l fo

ld o

n

the

op

po

site

sid

e.

The

resu

lts

of t

his

stu

dy

con

firm

th

e ef

ficac

y o

f b

oth

HA

gel

an

d h

ylan

B

plu

s g

el in

co

rrec

tin

g

nas

ola

bia

l fo

lds.

Bo

th

imp

rove

men

t an

d

du

rati

on

of t

reat

men

t ef

fect

wer

e g

reat

er w

ith

H

A g

el t

han

wit

h t

he

hyl

an B

plu

s, as

sh

ow

n b

y p

ost

trea

tmen

t WSR

S an

d

GA

IS a

sses

smen

ts.

Go

od

Ran

do

miz

ed C

on

tro

lled

Tri

al (R

CT

): N

o. o

f stu

die

s, 25

Car

ruth

ers

et a

l., 2

005

PMID

:164

1664

3

Do

ub

le-b

lind

RC

TC

anad

a/Pa

tien

ts

seek

ing

co

smet

ic

corr

ecti

on

of

mo

der

ate

to

seve

re n

aso

lab

ial

fold

s

150

(140

) 3,

4.5

, 6 m

o

Res

tyla

ne

Perl

ane,

1.3

ml

(avg

) (n

= 1

50)

Hyl

afo

rm, 1

.6 m

l (av

g)

(n =

150

)

Co

ntr

alat

eral

inje

ctio

n

of e

ach

fille

r in

to

the

mid

- or d

eep

d

erm

is n

aso

lab

ial

Res

tyla

ne

Perl

ane

pro

vid

es

a m

ore

du

rab

le a

esth

etic

im

pro

vem

ent

than

H

ylaf

orm

an

d o

ffer

s ac

cep

tab

le to

lera

bili

ty

Go

od

Car

ruth

ers

J et

al.,

20

03

PMID

:128

5937

8

Pro

spec

tive

, par

alle

l g

rou

p s

tud

y C

anad

a/A

du

lt fe

mal

e su

bje

cts

wit

h

mo

der

ate

to

seve

re g

lab

ella

r rh

ytid

es

38

32 w

k N

ASH

A (R

esty

lan

e)

(n =

19)

BTX

-A (B

oto

x) +

NA

SHA

(1

wk

late

r)

(n =

19)

1 cm

ab

ove

the

sup

rao

rbit

al n

otc

h

(on

bo

th s

ides

)

Go

od

Des

sy e

t al

., 20

08

PMID

:188

3304

3 R

and

om

ized

p

rosp

ecti

ve s

tud

y It

aly/

Pati

ents

wit

h

clea

r sig

ns

of

pre

mat

ure

faci

al

agin

g

100

1, 3

, 6, 1

2 m

o

Wip

elin

e (H

A c

on

cen

trat

ion

1.

6%)

Wip

elin

e (H

A c

on

cen

trat

ion

2.

0%)

Site

: fo

ld a

nd

wri

nkl

es

in t

he

face

Th

ree

sess

ion

s w

ith

4-

wk

inte

rval

s b

etw

een

th

em

.

The

effic

acy

of t

his

pro

du

ct,

Wip

elin

e, h

as b

een

cl

inic

ally

su

pp

ort

ed.

This

revi

taliz

ing

fille

r su

ccee

ded

in in

crea

sin

g

skin

ela

stic

ity

and

ton

e b

y d

erm

al h

ydra

tio

n. T

he

pro

ced

ure

is s

imp

le a

nd

m

inim

ally

inva

sive

. Th

is is

a

go

od

op

tio

n to

rest

ore

vi

talit

y an

d t

urg

idit

y o

f sk

in p

rese

nti

ng

sig

ns

of

agin

g.

Poo

r


April 2011

Glo

gau

et

al.,

200

8 PM

ID:1

8547

173

Pro

spec

tive

, blin

ded

, ra

nd

om

ized

co

ntr

olle

d s

tud

y

USA

/Gen

eral

p

op

ula

tio

n28

3 12

wk

Res

tyla

ne

(NA

SHA

-sm

all)

(n

= 1

42)

Perl

ane

(NA

SHA

-lar

ge)

Mid

face

vo

lum

e co

rrec

tio

n o

f th

e N

LFs

and

ora

l co

mm

issu

res

(mar

ion

ette

lin

es)

1,02

1 to

tal i

nje

ctio

n

site

s To

uch

-up

inje

ctio

ns

wer

e d

isco

ura

ged

to

par

alle

l clin

ical

p

ract

ice,

wh

ere

corr

ecti

on

is u

sual

ly

com

ple

ted

in a

si

ng

le s

essi

on

Loca

l ad

vers

e ev

ents

fo

llow

ing

inje

ctio

n w

ith

th

e N

ASH

A g

el fi

llers

u

sed

in t

his

stu

dy

wer

e re

late

d to

inve

stig

ato

r te

chn

iqu

e an

d n

ot

to d

iffer

ence

s in

th

e in

trin

sic

pro

per

ties

o

f th

e N

ASH

A a

gen

ts,

sug

ges

tin

g t

hat

m

od

erat

ing

th

e ra

te o

f in

ject

ion

of N

ASH

A fi

llers

m

ay le

ssen

th

e o

nse

t o

f lo

cal a

dve

rse

even

ts.

Go

od

Prel

imin

ary

log

isti

c re

gre

ssio

n a

nal

ysis

su

gg

este

d t

hat

ad

vers

e ev

ents

wer

e co

rrel

ated

w

ith

th

e fo

llow

ing

va

riab

les:

inje

ctio

n

typ

e, fa

nlik

e in

ject

ion

te

chn

iqu

e, in

ject

ion

vo

lum

e (g

reat

er m

ean

vo

lum

e), a

nd

co

rrec

tio

n

tim

e G

old

man

et

al.,

20

07

PMID

:174

5157

5

Ran

do

miz

ed,

eval

uat

or b

lind

ed,

clin

ical

tri

al

USA

/Pat

ien

ts w

ith

p

rom

inen

t n

aso

lab

ial f

old

s

36 (3

3)

56 d

R

esty

lan

e, a

lon

e an

d in

co

mb

inat

ion

wit

h la

ser/

RF/I

PL

Nas

ola

bia

l fo

lds

(tre

ated

wit

h H

A

gel

imp

lan

tati

on

on

o

ne

sid

e o

f th

e fa

ce

and

HA

gel

follo

wed

b

y o

ne

of t

he

no

nab

lati

ve la

ser/

RF/I

PL t

her

apie

s o

n

the

con

tral

ater

al

sid

e o

f th

e fa

ce)

Des

pit

e th

e lo

w n

um

ber

o

f via

ble

sam

ple

s, cl

inic

al a

nd

ext

rap

ola

ted

h

isto

log

ic d

ata

sup

po

rt

the

use

of l

aser

/RF/

IPL

trea

tmen

ts d

irec

tly

over

H

A g

el d

erm

al im

pla

nts

w

ith

ou

t af

fect

ing

pat

ien

t sa

fety

or i

mp

lan

t ef

ficac

y.

Fair

Ran

do

miz

ed

Co

ntr

olle

d T

rial

(R

CT

): N

o. o

f st

ud

ies,

25


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Gri

mes

et

al.,

2009

PM

ID:1

9735

512

Stu

dy

1:

do

ub

le- b

lind,

ra

nd

om

ized

cl

inic

al t

rial

St

ud

y 2:

op

en- l

abel

, ra

nd

om

ized

cl

inic

al t

rial

USA

/Pat

ien

ts w

ith

Fi

tzp

atri

ck s

kin

ty

pes

IV, V

, or V

I

Stu

dy

1: 1

60

Stu

dy

2: 1

19

24 w

k St

ud

y 1:

Ju

véd

erm

Ult

ra,

Ult

ra P

lus,

and

30

and

Z

ypla

st c

olla

gen

St

ud

y 2:

Hyl

afo

rm, H

ylaf

orm

Pl

us,

and

Cap

tiq

ue

Nas

ola

bia

l fo

lds

The

HA

fille

rs w

ere

effe

ctiv

e an

d w

ell

tole

rate

d in

ski

n o

f co

lor,

wit

h n

o o

ccu

rren

ces

of h

yper

tro

ph

ic o

r ke

loid

al s

carr

ing

or

hyp

erse

nsi

tivi

ty, a

nd

n

o in

crea

sed

inci

den

ce

of h

yper

pig

men

tati

on

o

r hyp

op

igm

enta

tio

n

com

par

ed w

ith

C

auca

sian

ski

n. T

he

fille

rs

pro

vid

ed s

mo

oth

, nat

ura

l lo

oki

ng,

an

d lo

ng

-las

tin

g

wri

nkl

e co

rrec

tio

n a

nd

a

go

od

saf

ety

pro

file

in

per

son

s w

ith

dar

ker s

kin

ty

pes

Fair

Ham

ilto

n e

t al

., 20

07

PMID

:180

8605

6

His

top

ath

olo

gic

st

ud

y o

f sam

ple

s fr

om

tw

o

pro

spec

tive

, m

aske

d R

CTs

USA

/Pat

ien

ts

un

der

go

ing

d

erm

al

aug

men

tati

on

of

NLF

s

433

0, 6

, 24

wk

Res

tyla

ne

Perl

ane

Bo

th N

LFs

NA

SHA

ad

min

istr

atio

n

do

es n

ot

elic

it c

linic

al

or l

abo

rato

ry e

vid

ence

fo

r cel

lula

r or h

um

ora

l im

mu

ne

resp

on

ses

in 9

8% o

f in

div

idu

als,

sup

po

rtin

g t

he

con

clu

sio

n th

at R

esty

lan

e an

d/o

r Per

lan

e ar

e n

ot

com

mo

nly

imm

un

og

enic

Fair

Ko

no

et

al.,

2008

PM

ID:1

8547

178

Ran

do

miz

ed,

eval

uat

or-

blin

d

stu

dy

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l

Jap

an

10 (1

0)

3, 6

, 9, 1

2 m

o

Res

tyla

ne,

sin

gle

cro

ss-

linke

d H

A (S

CH

A) (

n =

10)

Pura

gen

, do

ub

le c

ross

- lin

ked

HA

(DC

HA

) (n

=10

)

On

e si

de

of e

ach

p

atie

nt’s

gla

bel

lar

lines

was

tre

ated

w

ith

SC

HA

an

d

the

oth

er s

ide

was

tr

eate

d w

ith

DC

HA

Bo

th S

CH

A a

nd

DC

HA

ar

e eq

ual

ly e

ffec

tive

in

pro

du

cin

g a

n o

pti

mal

co

smet

ic re

sult

. DC

HA

p

rovi

des

a m

ore

du

rab

le

aest

het

ic im

pro

vem

ent

wh

en c

om

par

ed w

ith

SC

HA

in t

he

trea

tmen

t o

f g

lab

ella

r lin

es.

Poo

r


April 2011

Levy

et

al.,

PMID

:192

0732

2 Pr

osp

ecti

ve, d

ou

ble

-b

lind

RC

T Fr

ance

/Su

bje

cts

wit

h m

od

erat

e to

se

vere

bila

tera

l N

LFs

60N

on

e Ju

véd

erm

Ult

ra 3

, wit

h a

nd

w

ith

ou

t p

rein

corp

ora

ted

lid

oca

ine;

0.6

2 m

l

For e

ach

su

bje

ct, t

he

NLF

on

on

e si

de

was

ran

do

mly

as

sig

ned

to

trea

tmen

t w

ith

H

A+

lido

cain

e, a

nd

th

e o

pp

osi

te to

tr

eatm

ent

wit

h H

A

gel

alo

ne.

The

smo

oth

co

hes

ive

HA

g

el w

ith

pre

inco

rpo

rate

d

lido

cain

e re

sult

ed

in b

ette

r co

mfo

rt

du

rin

g N

LF in

ject

ion

an

d a

bet

ter i

nje

ctio

n

exp

erie

nce

th

an

an H

A g

el w

ith

ou

t p

rein

corp

ora

ted

lid

oca

ine.

Go

od

Lin

dq

vist

et

al.,

2005

PM

ID:1

5622

265

RC

T N

orw

ay a

nd

Sw

eden

/Pa

tien

ts w

ith

p

rom

inen

t N

LFs

68 (4

3)

2, 4

, 6, 9

, 12

mo

Pe

rlan

e (n

=68

) (o

ne

nas

ola

bia

l fo

ld)

Intr

ader

mal

inje

ctio

n

to t

he

nas

ola

bia

l fo

lds

Perl

ane

has

acc

epta

ble

lo

ng

-ter

m s

afet

y an

d

off

ers

a lo

ng

er-l

asti

ng

ae

sth

etic

imp

rove

men

t th

an Z

ypla

st.

Go

od

Zyp

last

(n =

68) (

con

tral

ater

al

NLF

) R

and

om

ized

Co

ntr

olle

d T

rial

(R

CT

): N

o. o

f st

ud

ies,

25

Lup

o e

t al

., 20

08

PMID

:181

7623

3 M

ult

icen

ter,

do

ub

le-b

lind,

ra

nd

om

ized

, w

ith

in- s

ub

ject

, co

ntr

olle

d s

tud

y

USA

/Su

bje

cted

p

rese

nti

ng

wit

h

seve

re N

LF ra

ted

as

3 o

r ab

ove

87 (8

2)

4, 8

, 12,

16,

20,

24,

48

wk

Juvé

der

m U

ltra

Plu

s (H

A)

1.7

ml f

or i

nit

ial t

reat

men

t, 0.

6 m

l fo

r rep

eate

d

trea

tmen

tZ

ypla

st (b

ovin

e co

llag

en)

Sub

ject

s ra

nd

om

ized

to

tre

atm

ent

wit

h

Juvé

der

m U

ltra

Pl

us

in o

ne

NLF

an

d Z

ypla

st in

th

e o

pp

osi

te N

LF.

The

mo

st s

ign

ifica

nt

find

ing

fr

om

th

e st

ud

y is

th

e ex

ten

ded

du

rati

on

of

corr

ecti

on

for J

uvé

der

m

Ult

ra P

lus,

par

ticu

larl

y fo

r sev

ere

fold

s. G

iven

th

at J

uvé

der

m o

utl

asts

th

e te

mp

ora

ry d

erm

al

fille

rs, p

erh

aps

it

sho

uld

be

com

par

ed to

se

mip

erm

eab

le fi

llers

R

adie

sse

and

Scu

lptr

a.

Go

od

70 (8

1%) o

f su

bje

cts

retu

rned

for

com

plim

enta

ry

rep

eate

d t

reat

men

t w

ith

Ju

véd

erm

Ult

ra

Plu

s, p

erfo

rmed

b

etw

een

24

and

36

wk

Man

et

al.,

2008

PM

ID:1

8430

173

Do

ub

le-b

lind,

co

mp

arat

ive

stu

dy

Pati

ents

ser

ved

as

Can

ada/

Fem

ale

pat

ien

ts w

ho

d

emo

nst

rate

d

der

mal

th

inn

ing

of

the

do

rsal

han

ds

10 (1

0)

1 w

k, 1

, 3, 6

mo

R

esty

lan

e (H

A),

1.4

ml (

n =

10

Co

smo

pla

st (C

olla

gen

), 2.

0 m

l (n

=10

)

Pati

ents

wer

e ra

nd

om

ized

to

rece

ived

tw

o v

ials

to

eit

her

th

eir r

igh

t o

r lef

t h

and

. Tw

o

vial

s o

f co

llag

en w

as

adm

inis

tere

d in

to

the

con

tral

ater

al

han

d.

Hya

luro

nic

aci

d p

rove

d

to b

e su

per

ior i

n

adm

inis

trat

ion

an

d

du

rati

on

to c

olla

gen

.

Go

od


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Mo

ers-

Car

pi e

t al

. 20

07

PMID

:180

8605

2

Mu

ltic

ente

r, b

lind

ed,

ran

do

miz

ed t

rial

Eu

rop

e/En

rolle

d

pat

ien

ts h

ad

mo

der

ate

or

seve

re N

LFs

205

(192

) 4,

8, 1

2 m

o

Rad

iess

e (C

aHA

), 2.

21 m

l to

tal v

olu

me

(n =

70)

Juvé

der

m 2

4 (H

A-1

A),

4.78

m

l to

tal v

olu

me

(n =

33

Juvé

der

m 2

4HV

(HA

-1B

), 2.

94

ml t

ota

l vo

lum

e (n

=33

) Pe

rlan

e (H

A-2

), 2.

89 m

l to

tal

volu

me

(n =

65)

Pati

ents

tre

ated

w

ith

eit

her

CaH

A

gel

or H

A fo

r th

e co

rrec

tio

n o

f bo

th

NLF

s. N

earl

y al

l p

atie

nts

(n =

189)

re

ceiv

ed a

tou

ch-u

p

trea

tmen

t at

4 m

o.

Bo

th C

aHA

gel

an

d

the

HA

pro

du

cts

dis

pla

y ad

equ

ate

and

co

mp

arab

le

safe

ty p

rofil

es. I

n t

his

co

ntr

olle

d s

tud

y, C

aHA

g

el ra

nke

d h

igh

est

in

pat

ien

t sa

tisf

acti

on

an

d

likel

iho

od

to re

turn

. Th

e m

ater

ial w

as m

ore

ef

fect

ive

and

lon

ger

la

stin

g t

han

eac

h H

A

in m

ain

tain

ing

NLF

au

gm

enta

tio

n. T

he

auth

ors

bel

ieve

CaH

A

gel

off

ers

adva

nta

ges

in

du

rab

ility

, pat

ien

t sa

tisf

acti

on

, an

d c

ost

, fo

r sa

fe c

orr

ecti

on

of N

LFs.

Go

od

Mo

ers-

Car

pi e

t al

. 20

08

PMID

:180

9319

9

Mu

ltic

ente

r, p

rosp

ecti

ve,

ran

do

miz

ed,

con

tro

lled,

sp

lit-

face

tri

al

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l.

Ger

man

y &

Sp

ain

/M

od

erat

e to

se

vere

NLF

s (3

or 4

o

n W

SRS)

60 (5

8)

6, 9

, 12

mo

R

adie

sse

Res

tyla

ne

Volu

me

req

uir

ed fo

r co

rrec

tio

n in

CaH

A

trea

ted

fold

was

30%

le

ss t

han

th

e vo

lum

e o

f N

ASH

A

Pati

ents

rece

ived

tw

o

inje

ctio

ns

3 m

o

apar

t. A

t th

e in

itia

l vi

sit,

pat

ien

t w

as

trea

ted

wit

h C

aHA

to

co

rrec

t o

ne

NLF

an

d N

ASH

A

to c

orr

ect

the

oth

er N

LF. A

t th

e 3

mo

vis

it, p

atie

nts

re

ceiv

ed a

tou

ch-

up

tre

atm

ent

in

bo

th fo

lds.

CaH

A w

as fo

un

d to

be

sig

nifi

can

tly

mo

re

effe

ctiv

e th

an N

ASH

A.

At

all t

ime

po

ints

, CaH

A

dem

on

stra

ted

lon

ger

la

stin

g re

sult

s an

d

gre

ater

imp

rove

men

t th

an N

ASH

A.

Go

od

Ran

do

miz

ed C

on

tro

lled

Tri

al (R

CT

): N

o. o

f stu

die

s, 25

Nar

ins

et a

l., 2

003

PMID

:127

8670

0 D

ou

ble

-blin

d R

CT

US/

corr

ecti

on

of

nas

ola

bia

l fo

lds

138

(138

)2,

4, 6

mo

R

esty

lan

e (n

= 1

38)

Zyp

last

(n =

138

In

ject

ion

of e

ach

m

ater

ial t

o

con

tral

ater

al

nas

ola

bia

l fo

lds

Res

tyla

ne

pro

vid

es m

ore

d

ura

ble

aes

thet

ic

imp

rove

men

t th

an

colla

gen

an

d is

wel

l to

lera

ted

Go

od


April 2011

Nar

ins

et a

l., 2

007

PMID

:180

8606

1 R

and

om

ized

, m

ult

icen

ter

wit

hin

- su

bje

ct

(sp

lit fa

ce)

no

nin

feri

ori

ty

stu

dy

USA

/Su

bje

cts

wit

h

app

roxi

mat

ely

sym

met

rica

l NLF

s cl

assi

fied

as

Gra

de

2 o

r gre

ater

on

M

FWS

164

(149

)6

mo

Der

mic

ol-

P35

(n =

149

) R

esty

lan

e (N

ASH

A)

(n =

149

)

NLF

s D

erm

ico

l-P3

5: m

ean

1.

48 m

l, 72

rece

ived

to

uch

-up

inje

ctio

ns

(0.5

9 m

l) R

esty

lan

e: m

ean

1.1

6 m

l. 73

rece

ived

to

uch

-up

inje

ctio

ns

(0.4

5 m

l)

The

effe

ctiv

enes

s o

f D

erm

ico

l-P3

5 is

m

ain

tain

ed fo

r at

leas

t 6

mo

an

d is

eq

uiv

alen

t to

N

ASH

A fo

r th

e co

rrec

tio

n

of N

LFs.

Go

od

Nar

ins

et a

l., 2

008

PMID

:185

4717

7 M

ult

icen

ter,

ran

do

miz

ed,

eval

uat

or-

blin

ded

st

ud

y Pa

tien

ts s

erve

d a

s th

eir o

wn

co

ntr

ol

USA

/Pat

ien

ts w

ith

m

od

erat

e to

se

vere

NLF

s

75 (6

3)

18 m

o in

teri

m o

f a

30 m

o s

tud

y R

esty

lan

e Pa

tien

ts w

ere

then

ra

nd

om

ized

to

retr

eatm

ent

at 4

.5 m

o a

nd

re

trea

tmen

t o

f th

e o

ther

N

LF a

t 9

mo.

All

pat

ien

ts re

ceiv

ed

an in

ject

ion

in b

oth

N

LFs

at t

he

first

vi

sit,

wit

h to

uch

-u

p in

ject

ion

s as

n

eed

ed a

t th

e 2

wk

follo

w-u

p v

isit

.

Imp

rove

men

ts s

een

aft

er

init

ial N

ASH

A fi

ller

trea

tmen

t p

ersi

sted

fo

r up

to 1

8 m

o w

ith

o

ne

retr

eatm

ent.

The

resp

on

se w

as e

qu

ival

ent

for r

etre

atm

ent

at 4

.5

and

9 m

o.

Fair

Nar

ins

et a

l., 2

008

PMID

:185

4717

9 R

and

om

ized

, wit

hin

su

bje

ct (s

plit

-fa

ce),

eval

uat

or-

blin

ded

tri

al

USA

/Clin

ical

evi

den

ce

of b

ilate

ral a

gin

g

def

ects

in t

he

nas

ola

bia

l are

a w

ith

wri

nkl

es

rate

d a

s 2

or

gre

ater

149

6, 9

, 12

mo

D

erm

ico

l-P3

5 (n

= 1

49)

Res

tyla

ne

(HA

) (n

=14

9)Ea

ch N

LF re

ceiv

ed o

ne

fille

r, o

ne

tou

ch-u

p

inje

ctio

n c

ou

ld

be

giv

en a

fter

2

wee

ks to

ob

tain

an

o

pti

mal

co

smet

ic

resu

lt (O

CR)

The

dat

a p

rese

nte

d in

dic

ate

that

th

e co

rrec

tio

n o

f N

LFs

ach

ieve

d w

ith

D

erm

ico

l-P3

5 in

ject

ion

is

mai

nta

ined

for u

p to

yea

r.

Fair

On

esti

et

al.,

2009

PM

ID:1

9454

518

Do

ub

le-b

lind

RC

TPa

tien

t se

rved

as

Ital

y/25

to 8

0 yr

wit

h

mar

ked

nas

ola

bia

l fo

lds

84 (6

8)

14 d

, 2, 4

, 6 m

o

Pura

gen

(n =

84)

Cap

tiq

ue

(n =

84)

Dep

th o

f in

ject

ion

an

d t

he

volu

me

to

be

inje

cted

wer

e at

th

e o

per

ato

r’s

dis

cret

ion

. Ea

ch p

atie

nt

rece

ived

Pu

rag

en in

on

e N

LF a

nd

Cap

tiq

ue

in t

he

con

tral

ater

al

fold

, in

a

Bo

th p

rod

uct

s u

sed

. Pu

rag

en a

nd

Cap

tiq

ue

are

equ

ally

eff

ecti

ve

and

saf

e in

elim

inat

ing

n

aso

lab

ial f

old

s. Th

e b

ioch

emic

al a

nd

st

ruct

ura

l ch

arac

teri

stic

s o

f Pu

rag

en e

nab

led

mo

re

lon

g-l

asti

ng

an

d s

tab

le

resu

lts

to b

e

Fair

Pin

sky

et a

l., 2

008

PMID

:190

8350

2 D

ou

ble

-blin

d, s

plit

- fa

ce R

CT

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l

USA

/Su

bje

cts

wit

h

fully

vis

ible

NLF

s 29

2 (2

80) 6

,9

mo

Ju

véd

erm

Ult

ra/J

uvé

der

m

Ult

ra P

lus

(n =

292)

Z

ypla

st b

ovin

e co

llag

en

(n =

292)

1.5

ml f

or i

nit

ial

trea

tmen

t, 0.

7 m

l fo

r re

pea

t tr

eatm

ent

Juvé

der

m U

ltra

an

d U

ltra

Pl

us

pro

vid

e lo

ng

-las

tin

g

clin

ical

imp

rove

men

t fo

r m

ore

th

an 9

mo

nth

s an

1

year

aft

er t

reat

men

t. re

spec

tive

ly. T

her

efo

re,

ind

ivid

ual

s tr

eate

d w

ith

th

ese

der

mal

fille

rs w

ill

req

uir

e re

pea

t tre

atm

ents

le

ss fr

equ

entl

y.

Fair


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Ran

do

miz

ed C

on

tro

lled

Tri

al (R

CT

): N

o. o

f stu

die

s, 25

Rao

et

al.,

2005

PM

ID:1

6416

642

RC

T U

SA/p

atie

nts

u

nd

erg

oin

g

corr

ecti

on

of

nas

ola

bia

l fo

lds

8 (8

) 12

wk

Res

tyla

ne

0.7

ml (

n =

8)

Co

ntr

alat

eral

inje

ctio

n

of e

ach

fille

r in

to

the

mid

- or d

eep

d

erm

is n

aso

lab

ial

Bo

th fi

llers

are

eff

ecti

ve fo

r ti

ssu

e au

gm

enta

tio

n

of t

he

nas

ola

bia

l fo

lds.

Res

tyla

ne

dem

on

stra

ted

h

igh

er p

atie

nt

sati

sfac

tio

n.

Fair

Hyl

afo

rm 1

.0 m

l (n

=8)

Va

rtan

ian

et

al.,

2005

PM

ID:1

6027

343

Pro

spec

tive

, se

qu

enti

al

Each

pat

ien

t se

rved

as

his

or h

er o

wn

co

ntr

ol

USA

/Gen

eral

p

op

ula

tio

n12

(8)

120

d

1. H

yalu

ron

idas

e an

d s

alin

e (n

=12

) 2.

Th

ree

diff

eren

t d

ose

s o

f h

yalu

ron

idas

e

Hya

luro

nid

ase

inje

cted

in

cu

tan

eus

area

s p

revi

ou

sly

inje

cted

w

ith

HA

(Res

tyla

ne)

.

Intr

ader

mal

hya

luro

nid

ase

inje

ctio

ns

can

be

use

d

to re

du

ce d

erm

al

aug

men

tati

on

fro

m

pre

vio

usl

y in

ject

ed

Res

tyla

ne.

A s

mal

l do

se o

f h

yalu

ron

idas

e (5

to 1

0 U

) m

ay b

e in

ject

ed in

itia

lly.

Go

od

Wei

nkl

e et

al.,

200

9 PM

ID:1

9735

519

RC

T U

S/Pa

tien

ts

un

der

go

ing

in

ject

ion

s to

th

e n

aso

lab

ial f

old

s

72 (7

2)

2 w

ks

Juvé

der

m (J

UV

) 1.6

ml (

max

) (n

=72

)Ju

véd

erm

+ li

do

cain

e (J

UV

+L)

1.6

ml (

max

) (n

=

72)

Inje

ctio

n o

f JU

V

and

JU

V+

L to

co

ntr

alat

eral

n

aso

lab

ial f

old

s

The

der

mal

fille

r fo

rmu

late

d

wit

h li

do

cain

e is

eff

ecti

ve

in re

du

cin

g p

roce

du

ral

pai

n d

uri

ng

co

rrec

tio

n

of f

acia

l wri

nkl

es a

nd

fo

lds

wh

ile m

ain

tain

ing

a

sim

ilar s

afet

y an

d

effe

ctiv

enes

s p

rofil

e to

th

e fil

ler w

ith

ou

t

Fair

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

13

Arl

ette

et

al.,

2008

PM

ID:1

8547

183

Pro

spec

tive

, no

n-

ran

do

miz

ed,

par

tial

ly b

lind

ed

Can

ada/

Sub

ject

s u

nd

erg

oin

g M

oh

s m

icro

gra

ph

ic

surg

ery

for b

asal

ce

ll ca

rcin

om

a o

f th

e N

LF a

rea

16

No

t re

po

rted

Juvé

der

m

NLF

Th

e p

red

om

inan

t lo

caliz

atio

n o

f in

ject

ed

HA

fille

r is

wit

hin

th

e su

bcu

tis.

A re

lati

vely

th

ink

NLF

der

mal

th

ickn

ess

(<1.

50 m

m)

likel

y p

recl

ud

es a

ccu

rate

in

ject

ion

of fi

ller i

nto

d

erm

al c

olla

gen

. Th

e re

sult

s su

gg

est

that

d

erm

al lo

caliz

atio

n o

f H

A fi

ller p

rod

uct

s is

no

t re

qu

ired

for a

n e

xcel

len

t co

smet

ic

Poo

r


April 2011

Bu

gg

e et

al.,

200

7 PM

ID:1

7944

679

Un

con

tro

lled

clin

ical

tr

ial

No

rway

/ H

IV-i

nfe

cted

p

atie

nts

old

er th

an

18 y

r of a

ge

wit

h

seve

re n

aso

gen

ian

at

rop

hy

20 (1

9)52

wk

Res

tyla

ne

Sub

Q 1

.5-2

.0 m

L in

eac

h c

hee

k 13

pat

ien

ts

also

rece

ived

a to

uch

-up

tr

eatm

ent

of R

esty

lan

e Su

bQ

1.0

mL

at w

k 4

Pati

ents

rece

ived

an

inje

ctio

n in

ea

ch c

hee

k in

th

e n

aso

gen

ian

are

a.

All

inje

ctio

ns

wer

e p

erfo

rmed

by

the

sam

e p

last

ic

surg

eon

at

an

ou

tpat

ien

t cl

inic

.

Res

tyla

ne

Sub

Q is

a u

sefu

l an

d w

ellt

ole

rate

d d

erm

al

fille

r fo

r tre

atin

g H

IV

po

siti

ve p

atie

nts

wit

h

faci

al li

po

atro

ph

y.

Poo

r

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

13

Car

ruth

ers

et a

l. 20

05

PMID

:158

4162

6

Clin

ical

Tri

al

Can

ada/

no

n-

pre

gn

ant,

no

n-

bre

astf

eed

ing

w

om

en a

ged

25

-60

yrs

wit

h

pro

min

ent

do

wn

turn

ed

mo

uth

co

rner

s

15 (1

4)

1wee

k 3,

4.5

, an

d

6 m

o

Res

tyla

ne

0.44

ml (

avg

up

per

lip

) an

d 1

.49

ml (

avg

lo

wer

lip

)

Seri

al p

un

ctu

re u

sin

g

a “p

ush

ah

ead

” te

chn

iqu

e ac

ross

th

e la

tera

l par

t o

f th

e u

pp

er a

nd

low

er

lip p

lus

intr

ader

mal

ex

ten

sio

n fr

om

ea

ch la

tera

l co

mm

issu

re

Res

tyla

ne

is s

afe

and

ef

fect

ive

as a

so

ft t

issu

e-au

gm

enti

ng

ag

ent

Poo

r

DeL

ore

nzi

et

al.,

Sub

cuta

neo

us

and

/or 2

006

PMID

:164

4204

0

Clin

ical

Tri

al

Can

ada/

pat

ien

ts

seek

ing

ch

in

and

/or c

hee

k au

gm

enta

tio

n

wit

h n

o a

esth

etic

fa

cial

su

rger

y in

th

e p

ast

12

mo

nth

s

571,

3, 6

, 9, 1

2 m

oR

esty

lan

e 10

.0 m

L (m

axim

um

)

Ave

rag

e in

ject

ion

of 2

.2 m

L (c

hee

k) a

nd

2.1

mL

(ch

in)

Sub

cuta

neo

us

and

/o

r su

pra

po

rio

stal

in

ject

ion

s

Res

tyla

ne

is w

ell t

ole

rate

d

and

mai

nta

ins

aest

het

ic

corr

ecti

on

of t

he

chee

ks

and

PM

:164

4204

0 ch

in

for a

t le

ast

3 m

o a

fter

tr

eatm

ent

Poo

r

DeL

ore

nzi

et

al.

2009

PM

:192

0732

0

Pro

spec

tive

, o

pen

lab

el s

tud

yC

anad

a/G

ener

al

po

pu

lati

on

571,

3, 6

, 9,

12 m

oR

esty

lan

e Su

bQ

.

Mea

n v

olu

mes

inje

cted

into

ea

ch c

hee

k w

as 2

.1 m

L,

and

into

eac

h c

hin

2.2

mL.

98 c

hee

ks, a

nd

16

chin

s.Th

irte

en p

atie

nts

re

ceiv

ed to

uch

-up

in

ject

ion

s at

20

site

s.

The

find

ing

s o

f th

is s

tud

y in

dic

ate

that

larg

e-p

arti

cle

stab

ilize

d

hya

luro

nic

aci

db

ased

g

el p

rovi

des

rela

tive

ly

lon

g-l

asti

ng

est

het

ic

corr

ecti

on

of t

he

chee

ks

and

ch

in. O

vera

ll, t

his

p

rod

uct

ap

pea

rs to

be

wel

l to

lera

ted,

an

d t

his

st

ud

y ra

ised

no

maj

or

safe

ty c

on

cern

s.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Den

ton

et

al.,

2007

PM

ID:1

7418

252

Pro

spec

tive

, o

bse

rvat

ion

al

clin

ical

stu

dy

Can

ada/

HIV

-po

siti

ve

mal

es w

ith

faci

al

lipo

atro

ph

y, m

ean

ag

e=47

.2yr

s

18 (1

4)

12 m

o

Perl

ane,

2.1

ml p

er s

ide

of

the

face

N

aso

lab

ial f

old

s, su

bm

alar

reg

ion

Th

e au

tho

rs’ s

tate

th

at

thei

r fin

din

gs

ind

icat

e th

at P

erla

ne

is a

feas

ible

o

pti

on

for c

orr

ecti

on

o

f fac

ial l

ipo

atro

ph

y.

The

pro

ced

ure

was

wel

l to

lera

ted

wit

ho

ut

any

lon

g-t

erm

seq

uel

ae

ob

serv

ed. P

atie

nts

ac

hie

ved

a s

ign

ifica

nt

imp

rove

men

t in

ap

pea

ran

ce la

stin

g fr

om

u

p to

1 y

ear.

Poo

r

Du

ran

ti e

t al

., 19

98

PMID

:986

5196

C

linic

al T

rial

It

aly/

pat

ien

ts

un

der

go

ing

au

gm

enta

tio

n

ther

apy

for

wri

nkl

es

158

(158

) 1,

2, 4

, 8 m

o

Res

tyla

ne

1.4

ml (

avg

) In

ject

ion

to t

he

mid

der

mis

of

the

gla

bel

la,

nas

ola

bia

l fo

lds,

ora

l co

mm

issu

re, a

nd

/o

r lip

s

Hya

luro

nic

aci

d g

el is

w

ell t

ole

rate

d a

nd

ef

fect

ive

for s

oft

tis

sue

aug

men

tati

on

of t

he

face

Poo

r

Han

et

al.,

2006

PM

ID:1

6508

353

Clin

ical

Tri

al

Ko

rea/

pat

ien

ts

un

der

go

ing

au

gm

enta

tio

n

rhin

op

last

y

11 (6

) 12

mo

C

ult

ure

d h

um

an fi

bro

bla

sts

susp

end

ed in

Res

tyla

ne

0.6-

1.0

ml

Inje

ctio

n in

to t

he

sub

cuta

neo

us

laye

r o

f th

e n

asal

do

rsu

m

Res

tyla

ne

wit

h s

usp

end

ed

cult

ure

d h

um

an

fibro

bla

sts

has

th

e p

ote

nti

al to

be

use

d a

s a

lon

g-l

asti

ng

inje

ctab

le

soft

- tis

sue

Poo

r

Jud

od

ihar

djo

et

al.

2008

PM

ID:1

8547

174

Op

en u

nco

ntr

olle

d

clin

ical

tri

al

UK

/Gen

eral

p

op

ula

tio

n25

(22)

24

hr,

4 w

k, 1

2 w

k Te

osy

al (h

ylau

ron

ic a

cid

) ~

0.83

ml p

er n

aso

lab

ial

fold

Sin

gle

inje

ctio

n in

to

each

nas

ola

bia

l fo

ld

The

mea

sure

men

ts

ob

tain

ed b

y th

e er

yth

ema

met

er a

nd

th

e in

frar

ed t

her

mo

met

er

corr

elat

ed w

ell w

ith

su

bje

ctiv

e cl

inic

al s

core

s. Th

e er

yth

ema

met

er a

nd

in

frar

ed t

her

mo

met

er

are

effe

ctiv

e to

ols

to

ob

ject

ivel

y m

easu

re

mild

infla

mm

atio

n p

ost

h

yalu

ron

ic a

cid

inje

ctio

n.

Poo

r

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

13

Ker

sch

er e

t al

., 20

08

PMID

:183

8461

9 Si

ng

le-c

ente

r, p

rosp

ecti

ve,

un

con

tro

lled

cl

inic

al t

rial

Ger

man

y/Sk

in t

ypes

I-

IV, s

agg

ing

/sl

acke

nin

g fa

cial

sk

in, a

ctin

ic

elas

tosi

s, lo

ss o

f sk

in e

last

icit

y,

>30

y

20 (1

9)

4, 8

, 12,

24

wk

Res

tyla

ne,

1.0

ml

Elig

ible

pat

ien

ts

rece

ived

bila

tera

l in

ject

ion

s o

f HA

in

the

low

er p

art

of

the

chee

ks in

th

ree

sess

ion

s (s

tart

, 4,

8 w

k)

The

stu

dy

sug

ges

ts

that

mic

rop

un

ctu

re

inje

ctio

ns

of N

ASH

A a

re

wel

l to

lera

ted

an

d c

an

imp

rove

der

mal

ela

stic

ity

and

red

uce

ski

n s

urf

ace

rou

gh

nes

s.

Poo

r


April 2011

Seri

al p

un

ctu

re

tech

niq

ue,

ap

pro

xim

atel

y 50

0.

02 m

l in

ject

ion

s p

er s

essi

on

Lo

we

et a

l. 20

06PM

:168

7546

8C

linic

al T

rial

US

and

UK

/ p

atie

nts

re

qu

esti

ng

au

gm

enta

tio

n o

f th

e u

pp

er c

hee

k o

r ch

in c

on

tou

r

72 (7

2)64

wk

Res

tyla

ne

Sub

Q 3

.9 m

LPe

rcu

tan

eou

s in

ject

ion

.

Slo

wly

inje

cted

wit

h

pal

pat

ion

. 5-8

in

ject

ion

tu

nn

els

crea

ted

wit

h

dep

osi

tio

n.

Res

tyla

ne

Sub

Q is

a u

sefu

l in

ject

able

ag

ent

to

aug

men

t an

d li

ft u

pp

er

chee

ks a

nd

reco

nto

ur

chin

s.

Poo

r

Ole

niu

s 19

98

PMID

:950

2839

C

linic

al T

rial

Sw

eden

/ p

atie

nts

u

nd

erg

oin

g

soft

tis

sue

aug

men

tati

on

for

faci

al w

rin

kles

113

(100

) 1,

2, 1

2, 2

6 w

k R

esty

lan

eN

aso

lab

ial f

old

s, g

lab

ella

r lin

es,

mo

uth

an

gle

w

rin

kles

, gen

eric

fa

cial

lin

es

Res

tyla

ne

fulfi

lled

th

e ex

pec

tati

on

s o

f giv

ing

sa

fe a

nd

eff

ecti

ve t

issu

e au

gm

enta

tio

n

Poo

r

Reu

ther

et

al.,

2009

PM

ID:1

9730

872

Sin

gle

-cen

tere

d,

pro

spec

tive

, o

pen

- lab

el

clin

ical

tri

al

Ger

man

y/h

ealt

hy

wo

men

ag

ed 3

0 yr

o

r old

er w

ith

loss

o

f ski

n e

last

icit

y

19

16 w

k R

esty

lan

e V

ital

(NA

SHA

), 1.

0ml a

t ea

ch o

f 3

trea

tmen

t se

ssio

ns

bila

tera

l in

ject

ion

s in

lo

wer

par

t o

f th

e fa

cial

ch

eeks

Trea

tmen

t o

f fac

ial s

kin

w

ith

NA

SHA

has

an

im

pac

t o

n t

he

intr

insi

c vi

sco

elas

tic

pro

per

ties

o

f th

e sk

in. T

he

pre

sen

t re

sult

s fr

om

th

is s

tud

y in

dic

ate

that

NA

SHA

ca

n im

pro

ve t

he

skin

’s vi

sco

elas

tic

beh

avio

r b

oth

by

tig

hte

nin

g t

he

skin

an

d b

y im

pro

vin

g

the

reco

il ca

pac

itie

s, m

akin

g it

ver

y in

tere

stin

g

as a

reju

ven

atio

n

app

roac

h. F

urt

her

in v

ivo

st

ud

ies,

idea

lly in

volv

ing

a

con

tro

l gro

up

, in

ad

dit

ion

to e

vid

ence

at

the

mo

lecu

lar l

evel

, are

re

qu

ired

to c

on

firm

th

ese

resu

lts

and

elu

cid

ate

a p

oss

ible

mec

han

ism

of

acti

on

.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Co

ho

rt S

tud

y N

um

ber

of s

tud

ies:

4 D

ista

nte

et

al.,

2009

PM

ID:1

9207

331

Pro

spec

tive

, op

en,

sin

gle

-cen

ter,

no

nco

mp

arat

ive

stu

dy

Ital

y/H

ealt

hy

wo

men

w

ith

mild

to

mo

der

ate

bra

chia

l p

tosi

s

16

90 d

R

esty

lan

e V

ital

, 1 m

l per

se

ssio

n p

er a

rm

Arm

Tr

eatm

ent

wit

h N

ASH

A c

an

imp

rove

th

e b

iop

hys

ical

p

rop

erti

es a

nd

ap

pea

ran

ce o

f th

e sk

in.

Poo

r

Thre

e se

ssio

ns

at

inte

rval

s o

f 30

d (

T0,

T30,

T60

). Fo

llow

-up

occ

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1492

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286

(286

) N

/A

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tyla

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ola

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nas

ola

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mel

ola

bia

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verm

illio

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olu

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enh

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men

t, g

lab

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r fo

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niq

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, vo

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nd

p

oin

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nd

an

esth

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r diff

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b

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Fran

ce/P

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llow

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pro

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er

der

mal

fille

rs u

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revi

ou

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Poo

r


April 2011

Cro

ss-s

ecti

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of s

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4320

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e. O

nly

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vers

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last

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ar.

Poo

r

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ort

Nu

mb

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et

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2007

PM:1

7761

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Cas

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Tr

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atri

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The

vari

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ASH

As

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or

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., 20

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8 R

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cas

e re

po

rt

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yea

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w

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12

yr, 2

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R

esty

lan

e M

elo

lab

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old

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on

sid

erin

g t

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po

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le

sid

e ef

fect

s w

ith

in

tro

du

cin

g a

fore

ign

su

bst

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into

th

e sk

in,

it is

cru

cial

th

at b

oth

th

e p

atie

nt

and

th

e p

hys

icia

n re

cog

niz

e th

e ri

sk o

f th

ese

pro

du

cts,

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th

e p

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nt

sho

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b

e in

form

ed a

bo

ut

the

po

ssib

le a

dve

rse

reac

tio

ns

fro

m u

sin

g a

n

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

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nC

on

clu

sio

ns

Gra

de

Bo

snia

k et

al.,

200

4 PM

ID:1

5545

531

Ret

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Bra

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pat

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1446

24

hr;

1 &

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, 6,

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Res

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Gla

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r lin

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p

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mb

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wit

h a

lin

ear t

hre

adin

g

tech

niq

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Fo

r bro

ader

d

epre

ssio

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fan

nin

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r cr

oss

-hat

chin

g

tech

niq

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wer

e u

sed,

su

pp

lem

ente

d

wit

h s

eria

l p

un

ctu

res.

The

du

rati

on

of t

he

NA

SHA

fil

ling

eff

ect

com

bin

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wit

h t

he

lack

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sub

stan

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co

mp

licat

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r ski

n p

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stin

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N

ASH

A a

n e

ffec

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tern

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oth

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tem

po

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inje

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fille

rs.

Poo

r

Inje

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ns

to t

he

gla

bel

lar a

rea,

n

aso

lab

ial f

old

s, o

ral c

om

mis

sure

, an

d li

ps

Cas

e Se

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/Rep

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Nu

mb

er o

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s: 39

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2007

PM

ID:1

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Cas

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Fille

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pla

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rep

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exc

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atie

nts

wh

o d

o n

ot

wis

h to

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su

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aso

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2 - p

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al a

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nkl

es

The

auth

ors

sta

te t

hat

p

atie

nts

wit

h s

arco

ido

sis

and

pat

ien

ts in

fect

ed

wit

h H

CV

sh

ou

ld b

e aw

are

of t

he

risk

of

fore

ign

bo

dy

gra

nu

lom

as

and

be

excl

ud

ed fr

om

an

y fil

ler i

nje

ctio

ns.

The

auth

ors

als

o fe

el t

hat

a

blo

od

test

for H

CV

sh

ou

ld

be

un

der

take

n b

efo

re

inje

ctio

n a

der

ma

fille

r.

Poo

r


April 2011

Do

use

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. 20

08

PMID

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8021

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Cas

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USA

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Cas

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der

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Fern

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cen

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200

3 PM

ID:1

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668

Ret

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rep

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Sp

ain

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Res

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nu

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ign

b

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HA

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isk

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Th

e fil

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rovi

de

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ger

th

an 1

yea

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an

be

fully

reve

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le

wit

h t

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ctio

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f h

yalu

ron

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e. T

he

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t is

qu

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in

th

is a

nec

do

tal s

erie

s w

as n

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be

safe

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r

Frie

dm

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02

PMID

:120

8167

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Ret

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ecti

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Euro

pe,

Can

ada,

A

ust

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, So

uth

A

mer

ica,

Asi

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Fin

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per

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resp

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uri

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e p

rod

uct

Poo

r

Cas

e Se

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N

um

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09

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sug

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Der

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nu

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s, as

was

se

en w

ith

th

e p

atie

nt

pre

sen

ted

in t

his

rep

ort

.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

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sio

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de

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. 20

06

PMID

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Ret

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r old

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man

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k - 3

mo

R

esta

lyn

e (h

yalu

ron

ic a

cid

) 27

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ge

nee

dle

lo

ng

itu

din

al

inje

ctio

n to

th

e m

elo

lab

ial,

gla

bel

lar,

and

per

iorb

ital

w

rin

kles

.

The

cau

se o

f lat

e in

flam

mat

ion

or

gra

nu

lom

a fo

rmat

ion

in

so

me

pat

ien

ts a

fter

in

ject

ion

of H

A is

no

t ye

t kn

ow

n, b

ut

wh

atev

er it

m

ay b

e, H

A R

esty

lan

e ca

nn

ot

be

con

sid

ered

in

no

cuo

us

and

pat

ien

ts

sho

uld

be

info

rmed

o

f th

ese

po

ssib

le

com

plic

atio

ns.

Poo

r

Go

din

et

al 2

006

PM:1

6549

735

Pro

spec

tive

Cas

e Se

ries

US/

pat

ien

ts

un

der

go

ing

faci

al

aug

men

tati

on

101

(61)

l10

mo

Rad

iess

e n

= 7

2

Rad

iess

e an

d R

esty

lan

e n

=29

Inje

ctio

n to

th

e n

aso

lab

ial f

old

s, u

pp

era

nd

low

er li

p

verm

illio

n b

ord

ers,

“lip

stic

k li

nes

” an

d

per

iora

l lin

es

Co

mb

inat

ion

gro

up

te

nd

ed to

hav

e g

reat

er

inte

rmed

iate

an

d o

vera

ll sa

tisf

acti

on

sco

res

than

th

e R

adie

sse

alo

ne

gro

up

.

Poo

r

Go

ldb

erg

et

al.,

2006

PM

ID:1

6985

414

Ret

rosp

ecti

ve c

ase

seri

es

USA

/155

pat

ien

ts,

(n =

41 m

ales

an

d

n=

114

fem

ales

w

ith

avg

ag

e o

f 53

yr)

155

(121

) 6-

12 m

o

Res

tyla

ne,

mea

n in

ject

ion

s w

ere:

0.96

ml a

t 1s

t in

ject

ion

0.87

ml a

t 2n

d in

ject

ion

0.78

ml a

t 3r

d in

ject

ion

Orb

ital

rim

, zyg

om

atic

an

d s

epta

l co

nflu

ence

ho

llow

s in

th

e ti

ssu

e p

lan

e d

eep

to t

he

orb

icu

lari

s o

culi

mu

scle

The

anat

om

y o

f th

e p

erio

rbit

al a

rea

is

tric

ky, b

ut

wit

h p

ract

ice,

p

atie

nce

, an

d fi

nes

se in

la

yin

g d

ow

n t

he

laye

rs o

f g

el, s

atis

fact

ori

ly s

mo

oth

co

nto

urs

can

be

crea

ted

. C

om

plic

atio

ns

incl

ud

ing

b

ruis

ing,

irre

gu

lar o

r lu

mp

y co

nto

ur,

blu

ish

o

r dar

k co

lor,

and

flu

id

accu

mu

lati

on

can

occ

ur.

The

auth

ors

’ fo

un

d t

hat

in

mo

st c

ases

, th

ese

wer

e n

ot

suffi

cien

tly

seve

re to

lim

it p

atie

nt

acce

pta

nce

. A

lth

ou

gh

th

e au

tho

rs’

reco

gn

ize

the

limit

atio

n

that

22

pat

ien

ts in

th

e st

ud

y h

ad n

o fo

llow

-u

p, t

he

anec

do

tal d

ata

sug

ges

t th

at t

he

maj

ori

ty

of p

atie

nts

are

sat

isfie

d

wit

h t

he

imp

rove

men

t.

Poo

r


April 2011

Hir

sch

et

al.,

2007

PM

ID:1

7373

195

Ret

rosp

ecti

ve c

ase

rep

ort

U

S/43

yr o

ld w

om

an

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der

m

Mu

ltip

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eep

der

mal

in

ject

ion

s al

on

g

the

nas

ola

bia

l fo

lds

usi

ng

a

linea

r th

read

ing

te

chn

iqu

e

This

cas

e p

rovi

des

in

cen

tive

to e

limin

ate

un

sup

ervi

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inje

ctio

ns

of fi

llin

g a

gen

ts b

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nq

ual

ified

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amed

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p

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el w

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lim

ited

tr

ain

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Th

e au

tho

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also

sp

ecu

late

th

at

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luro

nid

ase

may

h

ave

bee

n e

ffec

tive

at

trea

tin

g t

his

pat

ien

t b

y d

ecre

asin

g t

he

volu

me

of

the

hya

luro

nic

aci

d.

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 39

Ja

con

o 2

008

PMID

:182

0911

9 C

ase

seri

es

USA

/co

nse

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ve

pat

ien

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rese

tin

g

to a

faci

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last

ic

and

reco

nst

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ive

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ery

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ctic

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r in

ject

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lip

au

gm

enta

tio

n

66 p

atie

nts

re

ceiv

ing

137

tr

eatm

ents

9mo

s R

esty

lan

e Ve

rmili

on

, su

bve

rmili

on

, p

eris

tom

al, p

hilt

ral

colu

mn

, an

d o

ral

com

mis

sure

Au

tho

rs in

dic

ate

new

cla

ssifi

cati

on

o

f lip

an

ato

mic

al

zon

es fo

r dir

ecti

ng

in

ject

ion

Usi

ng

new

cla

ssifi

cati

on

o

f lip

an

ato

mic

al z

on

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to d

irec

t th

e in

ject

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o

f a n

on

-an

imal

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e st

abili

zed

hya

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nic

ac

id h

as in

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th

e au

tho

r’s a

bili

ty to

bet

ter

con

tro

l lip

sh

ape

and

siz

e in

lip

au

gm

enta

tio

n. T

his

te

chn

iqu

e w

as m

et w

ith

h

igh

pat

ien

t sa

tisf

acti

on

an

d n

o a

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cts.

Pers

iste

nce

of i

nje

cted

n

on

anim

al- s

ou

rces

st

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zed

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luro

nic

aci

d

was

sim

ilar t

o t

hat

see

n

in o

ther

stu

die

s.

Poo

r

Jham

et

al.,

PMID

:191

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0 C

ase

rep

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pre

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Vari

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56

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Up

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lip

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Poo

r

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Cas

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Nu

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e p

refe

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m

eth

od

for t

he

trea

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t o

f vo

lum

e lo

ss

to t

he

face

.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

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llo

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pT

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SA/2

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35

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24

10 d

0.

1-0.

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1)

30/3

2-g

aug

e in

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o

f Res

tyla

ne

in t

he

low

er e

yelid

The

auth

or s

tate

s th

at

corr

ecti

on

of t

ear t

rou

gh

d

efo

rmit

y w

ith

Res

tyla

ne

is a

co

mp

rom

ise

solu

tio

n

that

do

es n

ot

fix t

he

roo

t ca

use

of t

he

pro

ble

m,

bu

t it

can

imp

rove

its

app

eara

nce

wit

ho

ut

Poo

r

Len

nox

et

al.,

2007

PM

ID:1

7966

181

Cas

e re

po

rt

USA

/ 46

yr o

ld

fem

ale

pre

sen

ted

fo

r eva

luat

ion

o

f co

smet

ic

issu

es fo

llow

ing

m

aste

cto

my

and

si

lico

ne

imp

lan

t re

con

stru

ctio

n

1 4

wk

Juvé

der

m U

ltra

, 0.4

ml i

nto

ea

ch n

ipp

le in

eac

h o

f 2

trea

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t se

ssio

ns

nip

ple

s D

esp

ite

the

adve

nt

of

nu

mer

ou

s te

chn

iqu

es

use

d to

rest

ore

th

e n

ipp

le a

reo

la c

om

ple

x,

nip

ple

pro

ject

ion

has

re

mai

ned

un

sati

sfac

tory

. In

th

is c

ase,

th

e im

med

iate

resu

lts

of

usi

ng

hya

luro

nic

aci

d

fille

r was

exc

epti

on

ally

g

rati

fyin

g to

th

e p

atie

nt.

It w

ou

ld b

e w

ort

hw

hile

fo

r a la

rge

scal

e cl

inic

al

tria

l to

eva

luat

e th

e im

pac

t o

f hya

luro

ns

in

po

stm

aste

cto

my

pat

ien

ts

to d

eter

min

e ch

ang

e in

se

lf-ap

pea

ran

ce a

nd

sel

f-

este

em.

Poo

r

Low

e et

al.

2007

PM:1

7852

625

Cas

e re

po

rtU

S/ 3

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-old

fem

ale

wit

h m

ildly

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rop

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up

per

lip

an

d m

elo

men

tal

fold

s

1 (1

)1

hr f

ollo

win

g

trea

tmen

tR

esty

lan

e 1.

5 cc

Fille

r was

inje

cted

in

th

e u

pp

er li

p

and

mel

om

enta

l ar

ea a

fter

1%

X

ylo

cain

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erve

b

lock

was

giv

en fo

r an

aest

hes

ia

The

3D p

ho

tog

rap

hy

imag

ery

has

po

ten

tial

fo

r an

alyz

ing

th

e ch

ang

e o

f vo

lum

e b

oth

for

diff

eren

t p

arts

of t

he

face

, in

clu

din

g t

he

lips

in t

his

in

stan

ce.

Poo

r

Mal

ho

tra

2007

PM

ID:1

8071

111

Ret

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USA

/pat

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18

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5 6-

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Res

tyla

ne

Sub

-Q (h

yalu

ron

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acid

), 2m

l eac

h a

t 2

trea

tmen

ts

Intr

aco

nal

an

d

extr

aco

nal

po

ster

ior

orb

it

The

auth

ors

sta

te t

hat

th

is s

mal

l cas

e se

ries

su

gg

ests

th

e sa

fety

an

d

tole

rab

ility

of S

ub

-Q

into

th

e in

trac

on

al a

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Poo

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April 2011

Nyt

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PMID

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5 C

ase

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nas

al o

bst

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1 2

d

Res

tyla

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0.1

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dal

-med

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urf

ace

of t

he

up

per

late

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cart

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f th

e n

asal

val

ve

Up

per

late

ral c

arti

lag

e o

f th

e n

asal

val

ve

The

auth

ors

sta

tes

that

sp

read

er g

raft

inje

ctio

n

app

ears

to b

e a

viab

le,

no

nsu

rgic

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pti

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fo

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ng

nas

al

ob

stru

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n s

eco

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tern

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.

Poo

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Cas

e Se

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/Rep

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Nu

mb

er o

f stu

die

s: 39

O

du

nze

et

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2007

PM

ID:1

8090

767

Ret

rosp

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ase

seri

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USA

/pat

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av

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e o

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Fi

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tzp

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6-9

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R

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lan

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th

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erm

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pid

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n o

f th

e n

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old

s, fo

reh

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gla

bel

la,

mar

ion

ette

lin

es,

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sin

g

seri

al t

hre

adin

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un

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use

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mis

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stu

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dem

on

stra

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the

idea

th

at w

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per

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us

inje

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tech

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me

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Res

tyla

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ther

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Para

da

et a

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005

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9 H

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on

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nas

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bia

l fo

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l rh

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ent

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elo

ped

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he

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st b

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t. Th

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m

ay h

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n fr

om

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th

e au

tho

rs q

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n t

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kin

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Poo

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Pete

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:167

6465

8 R

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spec

tive

cas

e re

po

rt

Ger

man

y/48

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ld

man

1

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Res

tyla

ne

Gla

bel

lar a

rea

and

th

e ch

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Ev

en s

mal

l am

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mat

eria

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ca

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age

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reti

na.

Th

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ase

sho

uld

b

e a

war

nin

g t

hat

wid

ely

per

form

ed a

nd

sim

ple

p

roce

du

res

can

hav

e se

rio

us

com

plic

atio

ns.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

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ion

des

crip

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nC

on

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sio

ns

Gra

de

Req

uen

a et

al.,

200

1 PM

ID:1

1391

099

Ret

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seri

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Spai

n/5

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old

man

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yr o

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4 6-

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Art

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inio

n, i

s b

enefi

cial

an

d s

afe

wh

en it

is

use

d p

rop

erly

in s

mal

l am

ou

nts

for c

uta

neo

us

soft

tis

sue

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 39

R

oss

ner

et

al.,

2009

PM

ID:1

9207

327

Ret

rosp

ecti

ve c

ase

seri

es u

sin

g

Ber

lin re

gis

try

dat

a o

n a

dve

rse

reac

tio

ns

to

inje

ctab

le fi

llers

Ger

man

y/Pa

tien

ts

trea

ted

wit

h a

m

eth

acry

late

b

ased

fille

r wh

o

dev

elo

ped

a

reac

tio

n in

th

e sa

me

area

34

N/A

D

erm

aliv

e (h

dro

xyet

hyl

met

hac

ryla

te

and

eth

ylm

eth

acry

late

in

a fix

ed c

om

bin

atio

n w

ith

h

yalu

ron

ic a

cid

)

Fille

rs in

ject

ed in

95

area

s am

on

g t

he

34

pat

ien

ts.

Co

mm

on

are

as: N

LFs

(46.

3%)

Co

rner

s o

f th

e m

ou

th

(17.

9%)

Gla

bel

la (1

7.9%

) U

pp

er li

p (1

2.6%

)

Der

mal

ive

is a

lon

g-l

asti

ng

in

ject

able

fille

r wit

h a

b

iod

egra

dab

le p

art

(HA

) an

d a

no

nb

iod

egra

dab

le

par

t (m

eth

acry

late

).

Alt

ho

ug

h t

hes

e in

gre

die

nts

are

wid

ely

acce

pte

d a

s co

mp

atib

le

sub

stan

ces,

the

stu

dy

was

ab

le to

sh

ow

a la

rge

nu

mb

er o

f pat

ien

ts

dev

elo

pin

g a

dve

rse

Poo

r

Sch

wei

ger

et

al.

2008

PM

ID:1

8318

726

Cas

e re

po

rt

USA

/ 21

yr o

ld fe

mal

e b

orn

wit

h c

left

lip

, p

rio

r to

tre

atm

ent

had

rece

ived

12

reco

nst

ruct

ive

pro

ced

ure

s b

y cr

anio

faci

al

surg

eon

s;

com

pla

ined

of l

ip

asym

met

ry

1 A

pp

roxi

- mat

ely

4 m

o

Res

tyla

ne,

0.7

ml

up

per

lip

Th

e au

tho

rs b

elie

ve t

his

is

the

first

rep

ort

ed c

ase

usi

ng

hya

luro

nic

aci

d to

tr

eat

lip a

sym

met

ry in

a

pat

ien

t w

ith

cle

ft li

p,

wit

h s

ucc

essf

ul r

esu

lts.

The

auth

ors

co

ncl

ud

e th

at in

ject

able

so

ft

tiss

ue

fille

rs, e

spec

ially

h

yalu

ron

ic a

cid,

may

p

rovi

de

a m

inim

ally

in

vasi

ve m

eth

od

for

cosm

etic

en

han

cem

ent

in p

atie

nts

wit

h c

left

lip

wh

o d

esir

es fu

rth

er

aest

het

ic im

pro

vem

ent

afte

r su

rgic

al

Poo

r


April 2011

Sid

wel

l et

al.,

2004

PM

ID:1

5550

141

Ret

rosp

ecti

ve c

ase

rep

ort

U

K/4

0 yr

old

wh

ite

fem

ale

1 8,

12

mo

D

erm

aliv

e (s

ynth

etic

h

yalu

ron

ic a

cid

an

d

acry

lic h

yrd

og

el)

Inje

ctio

ns

of D

erm

aliv

e to

th

e n

aso

lab

ial

fold

s

The

auth

ors

po

int

ou

t th

at h

yalu

ron

ic a

cid

ar

e co

nsi

der

ed m

edic

al

dev

ices

, no

t d

rug

s, an

d a

s su

ch a

re s

cru

tin

ized

less

b

y th

e FD

A (D

erm

aliv

e is

no

t ye

t ap

pro

ved

). Th

ey a

dvo

cate

mo

re

com

pre

hen

sive

hu

man

te

stin

g p

rio

r to

ap

pro

val

of n

ew s

kin

fille

rs.

Poo

r

Sop

arka

r et

al.,

2005

PM

ID:1

5778

672

Ret

rosp

ecti

ve c

ase

rep

ort

U

S/62

yr o

ld w

om

an

1 7

d, 1

7 d,

5 m

o

2 0.

7 m

l syr

ing

es R

esty

lan

e N

aso

lab

ial f

old

s Th

e au

tho

rs a

re c

on

fuse

d

as to

th

e ca

use

–th

e tw

o

syri

ng

es w

ere

fro

m t

he

sam

e lo

t, an

d o

ne

was

p

rob

lem

atic

wh

ile t

he

oth

er w

as n

ot.

Poo

r

Tab

an e

t al

. 200

9PM

:196

1778

0C

ase

Seri

es/R

epo

rts

US/

Infa

nts

wit

h

con

gen

ital

eye

lid

mal

po

siti

on

s

5 (5

)M

ean

follo

w u

p

11.8

mo

Res

tyla

ne

0.5

mL

per

eye

lidH

yalu

ron

ic a

cid

gel

w

as in

ject

ed in

sm

all a

mo

un

ts

acro

ss t

he

len

gth

of

the

up

per

or l

ow

er

eyel

id

Hya

luro

nic

aci

d g

el s

ho

ws

pro

mis

e as

a n

ovel

, q

uic

k, s

afe,

eff

ecti

ve,

pre

dic

tab

le, n

on

-su

rgic

al

mea

ns

to m

anag

e a

vari

ety

of e

yelid

m

alp

osi

tio

ns.

Poo

r

Varg

as- M

ach

uca

et

al.,

2006

PM

ID:1

6625

084

Ret

rosp

ecti

ve c

ase

rep

ort

Sp

ain

/50

yr o

ld

wo

man

1

1 yr

2 m

o

Der

mal

ive

Peri

ora

l ski

n

Pati

ents

oft

en d

o n

ot

kno

w

the

fille

r in

ject

ed a

nd

it

is d

ifficu

lt to

ob

tain

su

ch in

form

atio

n fr

om

p

ract

itio

ner

s; t

his

mak

es

his

top

ath

olo

gic

stu

dy

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 39

W

olfr

am e

t al

., 20

06

PMID

:171

3573

5 R

etro

spec

tive

cas

e se

ries

A

ust

ria/

2 58

yr o

ld

wo

men

, 1 5

3 yr

old

w

om

an

3 3

mo

- 2

yr

New

fill,

Res

tyla

ne,

Der

maL

ive

Zyg

om

atic

arc

h,

eyel

ids,

fore

hea

d,

nas

ola

bia

l fo

lds,

chee

ks

Giv

en t

he

incr

easi

ng

use

o

f fille

rs, i

t m

igh

t b

e w

ort

h c

on

sid

erin

g

rem

ovin

g t

hem

fro

m

the

list

of m

edic

al it

ems

and

incl

ud

ing

th

em in

a

cate

go

ry w

ith

mo

re

stri

ng

ent

inve

stig

atio

n.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Co

llag

en F

iller

sR

and

om

ized

Co

ntr

olle

d T

rial

(R

CT

): N

o. o

f st

ud

ies,

13

Bau

man

n e

t al

. 200

7 PM

:180

8605

0 M

ult

icen

ter,

do

ub

le-m

aske

d,

ran

do

miz

ed,

wit

hin

- su

bje

ct

stu

dy

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l

USA

/Su

bje

cts

at le

ast

30 y

r an

d w

ith

fully

vi

sib

le b

ilate

ral

NLF

s th

at w

ere

app

roxi

mat

ely

sym

met

rica

l (b

oth

m

od

erat

e o

r bo

th

seve

re).

439

(423

) 24

wk

HA

: Ju

véd

erm

30

(J30

), Ju

véd

erm

Ult

ra (2

4HV

), Ju

véd

erm

Ult

ra P

lus

(30H

V) m

edia

n 1

.6 m

l (0

.8-5

.6 m

l)

Zyp

last

(cro

ss-l

inke

d b

ovin

e co

llag

en)

Sub

ject

s w

ere

ran

do

mly

ass

ign

ed

to re

ceiv

e o

ne

of

the

thre

e sm

oo

th-

gel

HA

fille

rs,

intr

ader

mal

ly to

th

e N

LF o

n o

ne

sid

e o

f th

e fa

ce. I

n a

ll su

bje

cts,

the

NLF

o

n t

he

oth

er s

ide

of

the

face

was

tre

ated

w

ith

Zyp

last

.

All

the

HA

der

mal

fille

rs

resu

lted

in a

mea

n

imp

rove

men

t (i.

e., a

re

du

ctio

n) f

rom

bas

elin

e in

NLF

sev

erit

y sc

ore

, cl

inic

ally

sig

nifi

can

t at

ea

ch t

ime

po

int.

Furt

her

, th

e H

A d

erm

al fi

llers

p

rovi

ded

lon

ger

-las

tin

g

clin

ical

co

rrec

tio

n t

hat

b

ovin

e co

llag

en.

Go

od

Vast

maj

ori

ty o

f su

bje

cts

had

on

ly

on

e tr

eatm

ent

visi

t.

The

new

sm

oo

th-g

el H

A

der

mal

fille

rs w

ere

hig

hly

eff

ecti

ve in

co

rrec

tin

g N

LFs

for

6 m

o o

r lo

ng

er a

fter

tr

eatm

ent.

The

maj

ori

ty

of s

ub

ject

s ac

hie

ved

o

pti

mal

co

rrec

tio

n w

ith

o

nly

a s

ing

le in

ject

ion

o

f th

e H

A d

erm

al fi

ller,

and

th

e fil

lers

wer

e al

so

sim

ilarl

y w

ell t

ole

rate

d.

An

ove

rwh

elm

ing

m

ajo

rity

of s

ub

ject

s ex

pre

ssed

a p

refe

ren

ce

for t

he

smo

oth

- gel

HA

d

erm

al fi

llers

ove

r bov

ine

colla

gen

. C

oh

en e

t al

. 200

4 PM

:154

6840

6 R

CT

US/

pat

ien

ts a

t le

ast

18 y

ears

of

age

pre

sen

tin

g

for g

lab

ella

r, n

aso

lab

ial f

old

s, ra

dia

l up

per

lip

lin

es, m

ario

net

te

lines

co

rrec

tio

n

251

(251

) (11

1 at

12

1, 3

, 6, 1

2 m

o

Art

eco

ll n

=12

8 Z

yder

m II

or Z

ypla

st n

=12

3 Tu

nn

elin

g te

chn

iqu

e:

lab

ella

, nas

ola

bia

l fo

lds,

rad

ial u

pp

er

lip li

nes

, mar

ion

ette

lin

es

Stu

dy

dem

on

stra

ted

th

e re

lati

ve s

afet

y an

d

effe

ctiv

enes

s o

f Art

eco

ll re

lati

ve to

th

at o

f co

llag

en

Go

od


April 2011

Co

hen

et

al. 2

006

PM:1

6936

546

RC

T (d

ou

ble

-blin

d)

US/

pat

ien

ts w

ith

w

rin

kles

of t

he

gla

bel

la, n

aso

lab

ial

fold

s, ra

dia

l up

per

lip

lin

es, a

nd

co

rner

s o

f th

e m

ou

th; t

reat

ed

wit

h P

MM

A fi

ller

in p

ivo

tal R

CT

(Co

hen

200

4)

251

(233

) (69

4 to

5

year

) 1,

3, 6

, 12

mo

4-5

ye

ars

Art

eFill

(am

ou

nt

no

t sp

ecifi

ed) n

=12

8 C

olla

gen

(am

ou

nt

no

t sp

ecifi

ed) n

=12

3

Inje

ctio

n a

t th

e g

lab

ella

, nas

ola

bia

l fo

lds,

rad

ial u

pp

er

lip li

nes

, or c

orn

ers

of t

he

mo

uth

Stu

dy

dem

on

stra

ted

th

e ov

eral

l saf

ety

and

ef

fect

iven

ess

of A

rteF

ill

rela

tive

to a

co

llag

en

con

tro

l. Ef

fect

iven

ess

was

dem

on

stra

ted

for a

ll ar

eas

trea

ted

.

Go

od

Ran

do

miz

ed C

on

tro

lled

Tri

al (R

CT

): N

um

ber

of s

tud

ies,

13G

rim

es e

t al

. 200

9 PM

:197

3551

2 St

ud

y 1:

d

ou

ble

- blin

d,

ran

do

miz

ed

clin

ical

tri

al

Stu

dy

2: o

pen

- lab

el,

ran

do

miz

ed

clin

ical

tri

al

USA

/pat

ien

ts w

ith

Fi

tzp

atri

ck s

kin

ty

pes

IV, V

, or V

I

Stu

dy

1: 1

60

Stu

dy

2: 1

19

24 w

k St

ud

y 1:

Ju

véd

erm

Ult

ra,

Ult

ra P

lus,

and

30

and

Z

ypla

st c

olla

gen

St

ud

y 2:

Hyl

afo

rm, H

ylaf

orm

Pl

us,

and

Cap

tiq

ue

Nas

ola

bia

l fo

lds

The

HA

fille

rs w

ere

effe

ctiv

e an

d w

ell

tole

rate

d in

ski

n o

f co

lor,

wit

h n

o o

ccu

rren

ces

of h

yper

tro

ph

ic o

r ke

loid

al s

carr

ing

or

hyp

erse

nsi

tivi

ty, a

nd

n

o in

crea

sed

inci

den

ce

of h

yper

pig

men

tati

on

o

r hyp

op

igm

enta

tio

n

com

par

ed to

Cau

casi

an

skin

. Th

e fil

lers

pro

vid

ed

smo

oth

, nat

ura

l-lo

oki

ng,

an

d lo

ng

-las

tin

g w

rin

kle

corr

ecti

on

an

d a

go

od

sa

fety

pro

file

in p

erso

ns

wit

h

Fair

Lin

dq

vist

et

al. 2

005

PM:1

5622

265

RC

T N

orw

ay a

nd

Sw

eden

/Pa

tien

ts w

ith

p

rom

inen

t n

aso

lab

ial f

old

s

68 (4

3)

2, 4

, 6, 9

, 12

mo

Pe

rlan

e n

=68

(on

e n

aso

lab

ial

fold

)

Zyp

last

n=

68 (c

on

tral

ater

al)

Intr

ader

mal

inje

ctio

n

to t

he

nas

ola

bia

l fo

lds

Perl

ane

has

acc

epta

ble

lo

ng

-ter

m s

afet

y an

d

off

ers

a lo

ng

er-l

asti

ng

ae

sth

etic

imp

rove

men

t th

an Z

ypla

st

Go

od

Lup

o e

t al

. 200

8 PM

:181

7623

3 M

ult

icen

ter,

do

ub

le-b

lind,

ra

nd

om

ized

, w

ith

in- s

ub

ject

, co

ntr

olle

d s

tud

y

USA

/Su

bje

cted

p

rese

nti

ng

wit

h

seve

re N

LF ra

ted

as

3 o

r ab

ove

87 (8

2)

4, 8

, 12,

16,

20,

24,

48

wk

Juvé

der

m U

ltra

Plu

s (H

A)

1.7

ml f

or i

nit

ial t

reat

men

t, 0.

6 m

l fo

r rep

eate

d

trea

tmen

t

Sub

ject

s ra

nd

om

ized

to

tre

atm

ent

wit

h

Juvé

der

m U

ltra

Pl

us

in o

ne

NLF

an

d Z

ypla

st in

th

e o

pp

osi

te N

LF.

70 (8

1%) o

f su

bje

cts

retu

rned

for

com

plim

enta

ry

rep

eate

d t

reat

men

t w

ith

Ju

véd

erm

Ult

ra

Plu

s, p

erfo

rmed

b

etw

een

24

and

36

wk

The

mo

st s

ign

ifica

nt

find

ing

fr

om

th

e st

ud

y is

th

e ex

ten

ded

du

rati

on

of

corr

ecti

on

for J

uvé

der

m

Ult

ra P

lus,

par

ticu

larl

y fo

r sev

ere

fold

s. G

iven

th

at J

uvé

der

m o

utl

ats

the

tem

po

rary

der

mal

fil

lers

, per

hap

s it

sh

ou

ld b

e co

mp

ared

to

sem

iper

mea

ble

fille

rs

Rad

iess

e an

d S

culp

tra.

Go

od


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Man

et

al. 2

008

PM:1

8430

173

Do

ub

le-b

lind,

co

mp

arat

ive

stu

dy

Pati

ents

ser

ved

as

Can

ada/

Fem

ale

pat

ien

ts w

ho

d

emo

nst

rate

d

der

mal

th

inn

ing

of

the

do

rsal

han

ds

10 (1

0)

1 w

k, 1

, 3, 6

mo

R

esty

lan

e (H

A),

1.4

ml n

=10

Co

smo

pla

st (C

olla

gen

), 2.

0 m

l n=

10

Pati

ents

wer

e ra

nd

om

ized

to

rece

ived

tw

o v

ials

to

eit

her

th

eir r

igh

t o

r lef

t h

and

. Tw

o

vial

s o

f co

llag

en w

as

adm

inis

tere

d in

to

the

con

tral

ater

al

han

d.

Hya

luro

nic

aci

d p

rove

d

to b

e su

per

ior i

n

adm

inis

trat

ion

an

d

du

rati

on

to c

olla

gen

.

Go

od

Mo

nst

rey

et a

l. 20

07PM

:175

7257

9 b

lind

ed, r

and

om

ized

cl

inic

al t

rial

B

elg

ium

an

d Is

rael

/p

atie

nts

wit

h

clin

ical

evi

den

ce

of b

ilate

ral a

gin

g

def

ects

in t

he

nas

ola

bia

l are

a

12

18 m

o

Evo

len

ce, 1

.72m

l Z

ypla

st, 1

.72m

ln

aso

lab

ial f

old

s Th

e re

sult

s o

f th

is c

linic

al

stu

dy

sug

ges

t th

at

Evo

len

ce c

ou

ld p

rovi

de

a su

bst

anti

ally

imp

rove

d

alte

rnat

ive

to t

he

exis

tin

g

trea

tmen

t av

aila

ble

. Th

e re

sult

s o

f th

is s

tud

y m

ust

b

e co

nfir

med

in fu

ture

cl

inic

al s

tud

ies.

Go

od

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

Nu

mb

er o

f S

tud

ies:

13

Nar

ins

et a

l. 20

03

PM:1

2786

700

Do

ub

le-b

lind

RC

T U

S/co

rrec

tio

n o

f n

aso

lab

ial f

old

s 13

8 (1

38)

2, 4

, 6 m

o

Res

tyla

ne

(n=

138

)Z

ypla

st (n

= 1

38)

Inje

ctio

n o

f eac

h

mat

eria

l to

co

ntr

alat

eral

n

aso

lab

ial f

old

s

Res

tyla

ne

pro

vid

es m

ore

d

ura

ble

aes

thet

ic

imp

rove

men

t th

an

colla

gen

an

d is

wel

l to

lera

ted

Go

od

Nar

ins

et a

l. 20

08

PM:1

8547

179

Ran

do

miz

ed, w

ith

in

sub

ject

(sp

lit-

face

), ev

alu

ato

r-b

lind

ed t

rial

USA

/Clin

ical

evi

den

ce

of b

ilate

ral a

gin

g

def

ects

in t

he

nas

ola

bia

l are

a w

ith

wri

nkl

es

rate

d a

s 2

or

gre

ater

149

6, 9

, 12

mo

D

erm

ico

l-P3

5 (n

= 1

49)

Res

tyla

ne

(HA

) (n

=14

9)

Each

NLF

rece

ived

on

e fil

ler,

on

e to

uch

-up

in

ject

ion

co

uld

b

e g

iven

aft

er 2

w

eeks

to o

bta

in a

n

op

tim

al c

osm

etic

re

sult

(OC

R)

The

dat

a p

rese

nte

d in

dic

ate

that

th

e co

rrec

tio

n o

f N

LFs

ach

ieve

d w

ith

D

erm

ico

l-P3

5 in

ject

ion

is

mai

nta

ined

for u

p to

yea

r.

Fair

Scla

fan

i et

al. 2

001

PM:1

1368

660

RC

T U

S/p

atie

nts

no

t al

lerg

ic to

bov

ine

colla

gen

10 (1

0)

1, 3

, 6, 9

, 12

mo

A

lloD

erm

5.0

mm

(n=

10)

Allo

Der

m p

lace

d

surg

ical

ly in

a

sub

der

mal

pla

ne

in

on

e p

ost

auri

cula

r cr

ease

Allo

Der

m a

re s

tab

le a

s so

ft

tiss

ue

fille

rs a

nd

are

su

per

ior t

o Z

ypla

st w

ith

re

gar

ds

to re

abso

rpti

on

Go

od

Zyp

last

0.5

ml (

n=

10)

Zyp

last

inje

cted

in a

su

bd

erm

al p

lan

e in

th

e o

pp

osi

te

po

stau

ricu

lar c

reas

e


April 2011

Scla

fan

i et

al. 2

002

PM:1

2437

432

RC

T U

S/p

atie

nts

wit

h a

ge-

re

late

d c

han

ges

in

th

e si

ze a

nd

co

nto

ur o

f th

e lip

44 (4

4)

3, 6

, 9, 1

2 m

o

Cym

etra

(n=

19)

Zyp

last

(n=

25)

Inje

ctio

n to

th

e u

pp

er li

p b

etw

een

th

e o

rbic

ula

ris

ori

s m

usc

le a

nd

th

e ov

erly

ing

m

uco

cuta

neo

us

jun

ctio

n o

f th

e u

pp

er li

p

Cym

etra

incr

ease

s th

e u

pp

er li

p b

ulk

, ver

mili

on

, an

d lo

wer

lip

pro

ject

ion

Go

od

Smit

h e

t al

.200

7PM

:180

8604

8R

and

om

ized

, ev

alu

ato

r-b

lind

ed, b

ilate

ral,

pro

spec

tive

co

mp

aris

on

USA

/Po

ten

tial

su

bje

cts

wer

e re

qu

ired

to

hav

e sy

mm

etri

c,

mo

der

atet

o- d

eep

N

LFs

117

(113

)1,

3, 6

mo

Rad

iess

e (C

olla

gen

)

Co

smo

pla

st (C

aHA

)

Each

sid

e w

as

trea

ted

un

til,

in

the

jud

gm

ent

of

the

inve

stig

ato

r, an

op

tim

al re

sult

w

as a

chie

ved

. At

2 w

k fo

llow

ing

tr

eatm

ent,

sub

ject

s co

uld

rece

ive

tou

ch-u

p in

ject

ion

s at

th

e d

iscr

etio

n

of t

he

ph

ysic

ian

O

ccu

rred

at

2 w

k in

terv

als,

max

imu

m

of t

wo

ad

dit

ion

al

trea

tmen

t se

ssio

ns.

Qu

alify

ing

su

bje

cts

rece

ived

CaH

A

pro

du

ct o

n o

ne

sid

e, a

nd

th

e H

C

pro

du

ct o

n t

he

oth

er.

The

CaH

A-b

ased

pro

du

ct

giv

es s

ign

ifica

ntl

y lo

ng

er la

stin

g c

orr

ecti

on

o

f NLF

s co

mp

ared

to

hu

man

co

llag

en. F

ewer

in

ject

ion

s an

d le

ss to

tal

mat

eria

l are

req

uir

ed. T

he

adve

rse

even

t p

rofil

es o

f th

e tw

o fi

llers

are

sim

ilar.

Go

od

Co

llag

en F

iller

s C

on

tro

lled

Clin

ical

Tri

al N

um

ber

of

stu

die

s: 2

Sc

lafa

ni e

t al

. 200

0 PM

:109

2542

4 C

on

tro

lled

Clin

ical

Tr

ial

US/

pat

ien

ts

un

der

go

ing

faci

al

asth

etic

su

rger

y w

ith

ski

n e

xcis

ion

5 (3

) 2,

4, 1

2 w

k A

uto

log

en 0

.5 m

l n=

5 Z

ypla

st 0

.5 m

l n=

5 Tw

o in

ject

ion

s o

f ea

ch m

ater

ial

con

tral

ater

aly

to t

he

po

stau

ricu

lar a

rea

Au

tolo

go

us

colla

gen

d

isp

ersi

on

may

be

a vi

able

alt

ern

ativ

e to

b

ovin

e co

llag

en

Poo

r

Scla

fan

i et

al. 2

002

PM:1

2187

346

Co

ntr

olle

d c

linic

al

tria

l U

S/h

ealt

hy

adu

lts

20 (1

7)

4 an

d 1

2 w

k D

erm

alo

gen

0.1

ml n

= 2

0

Zyp

last

0.1

ml n

= 2

0

Inje

ctio

n b

ehin

d t

he

con

tral

ater

al e

ar

Der

mal

og

en is

saf

e, e

asily

ad

min

iste

red,

an

d w

ell

tole

rate

d s

imila

rly

to

Zyp

last

Fair


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of

stu

die

s: 2

Sh

osh

ani e

t al

. 200

7 PM

:180

8605

3 Si

ng

le-c

ente

r o

pen

-lab

el,

un

con

tro

lled

st

ud

y to

exa

min

e th

e p

ote

nti

al o

f Ev

ole

nce

imp

lan

t to

elic

it a

llerg

ic

reac

tio

ns

USA

/Gen

eral

p

op

ula

tio

n53

0 30

min

, 72

hr,

30 d

Ev

ole

nce

, 0.1

ml

Enro

lled

su

bje

cts

rece

ived

an

in

trad

erm

al

inje

ctio

n in

th

e le

ft fo

rear

m, a

nd

a

seco

nd

inje

ctio

n in

th

e ri

gh

t fo

rear

m

afte

r 2 w

k

Du

e to

a lo

w p

ote

nti

al fo

r h

yper

sen

siti

vity

, Evo

len

ce

intr

ader

mal

ski

n te

stin

g

do

es n

ot

app

ear t

o

be

nec

essa

ry, a

s it

is

com

par

able

to t

hat

of

oth

er d

erm

al fi

llers

th

at

can

be

use

d s

afel

y an

d

effe

ctiv

ely

wit

ho

ut

a

Poo

r

Co

ho

rt S

tud

y N

um

ber

of s

tud

ies:

1 B

ou

lle e

t al

. 200

9PM

:192

8869

2O

pen

, mu

ltic

ente

r, re

tro

spec

tive

d

ata

colle

ctio

n

stu

dy

Bel

giu

m, S

wed

en/

Pati

ents

wh

o

had

un

der

go

ne

Der

mic

ol-

P35

30G

lip

inje

ctio

ns

Safe

ty: 5

7Ef

ficac

y: 5

14-

10 m

oD

erm

ico

l-P3

5 30

GD

ata

colle

cted

fro

m

pat

ien

ts to

en

han

ce

or r

esto

re t

he

con

tou

r of t

he

up

per

an

d/o

r lo

wer

lip

in e

ith

er t

he

verm

illio

n b

ord

er,

the

bo

dy

of t

he

lip,

or b

oth

.

Thes

e re

tro

spec

tive

st

ud

y re

sult

s su

pp

ort

D

erm

ico

l-P3

5 30

G a

s a

safe

an

d e

ffec

tive

tr

eatm

ent.

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 17

B

rau

n e

t al

. 200

8PM

:185

6159

Pro

spec

tive

cas

e se

ries

USA

/fem

ale

pat

ien

ts

pre

sen

ted

to

clin

ic fo

r lip

en

han

cem

ent

or

aug

men

tati

on

201

yrEv

ole

nce

, 1.0

ml

Bo

dy

of l

ip, m

assa

ge

tech

niq

ue

use

d

imm

edia

tely

aft

er

inje

ctio

n

Wit

h re

gar

ds

to E

vole

nce

, it

is t

he

auth

ors

exp

erie

nce

th

at it

sh

ou

ld n

ot

be

inje

cted

into

th

e lip

s, as

Evo

len

ce h

as fa

r to

o

hig

h a

n in

cid

ence

of

un

des

irab

le n

od

ule

fo

rmat

ion

. Co

lbar

Li

fesc

ien

ce s

ho

uld

u

pd

ate

and

cla

rify

th

e p

rod

uct

info

rmat

ion

fo

r Evo

len

ce fo

r th

e b

enefi

t o

f ph

ysic

ian

s an

d

pat

ien

ts.

Poo

r

de

Lace

rda

et a

l. 20

07

PM:1

8086

060

Cas

e re

po

rt

Bra

zil/

2 fe

mal

es, a

ged

45

an

d 5

2yo

2

Cas

e 1

- 1 y

r

Cas

e 2

- 4m

os

Cas

e 1

- Evo

len

ce (p

orc

ine

colla

gen

), 2m

l

Cas

e 2

- Vo

lum

a (H

yalu

ron

ic

acid

), 2m

l

Cas

e 1

- no

se,

nas

ola

bia

l fo

lds,

and

lip

s

Cas

e 2

- no

se,

nas

ola

bia

l fo

lds,

and

lip

s

Fille

r rh

ino

pla

sty

rep

rese

nts

an

exc

elle

nt

alte

rnat

ive

for p

atie

nts

wh

o d

o n

ot

wis

h to

un

der

go

su

rger

y.

It is

a m

inim

ally

inva

sive

an

d c

ost

-eff

ecti

ve o

ffice

p

roce

du

re.

Poo

r


April 2011

Fisc

her

et

al. 2

007

PM:1

7438

184

Ret

rosp

ecti

ve c

ase

rep

ort

G

erm

any/

48 y

r old

w

om

an

1 10

yr

Art

eco

ll In

ject

ion

s in

th

e u

pp

er

and

low

er li

ps,

nas

ola

bia

l gro

oves

, an

d g

lab

ella

This

rep

ort

sh

ow

s th

e p

ote

nti

al lo

ng

-ter

m

risk

s; t

he

risk

of s

ever

e in

tera

ctio

n w

ith

in

terf

ero

n o

r oth

er

imm

un

ost

imu

lato

ry

med

icat

ion

s sh

ou

ld b

e in

clu

ded

in t

he

con

sen

t fo

rm fo

r in

ject

able

ae

sth

etic

mic

roim

pla

nts

.

Poo

r

Ho

pki

ns

et a

l. 20

09

PM:1

9260

892

Cas

e se

ries

U

K/4

1 fe

mal

es a

nd

17

mal

es, m

ean

ag

e=36

yrs;

58

min

imu

m fo

llow

u

p w

as 6

mo,

w

ith

n=

40

un

der

go

ing

fu

rth

er re

view

at

12m

os

and

n=

31

at 2

4mo

s

Perm

aco

l (ac

ellu

lar c

ross

- lin

ked

po

rcin

e d

erm

al

colla

gen

)

Nas

al re

gio

n d

uri

ng

rh

ino

pla

sty

The

auth

ors

aw

ait

lon

g-t

erm

fo

llow

-up

, bu

t st

ate

that

th

eir 5

yr e

xper

ien

ce

wit

h P

erm

aco

l has

bee

n

extr

emel

y p

rom

isin

g.

The

auth

ors

sta

te

that

Per

mac

ol i

s an

id

eal i

mp

lan

t m

ater

ial,

allo

win

g e

xcel

len

t nat

ura

l re

sult

s co

mp

lem

enti

ng

th

e u

se o

f au

tolo

go

us

Poo

r

Ino

ue

et a

l. PM

:183

1709

7 C

ase

rep

ort

Ja

pan

/50

yr o

ld

fem

ale

wit

h n

o

pri

or c

osm

etic

su

rger

y

1 43

d

Res

tyla

ne

and

Sh

eba

(co

llag

en)

Nas

al t

ip (R

esty

lan

e)

and

up

per

lip

an

d

nas

ola

bia

l fo

ld a

nd

u

pp

er v

erm

ilio

n

(co

llag

en)

The

auth

ors

sta

te t

hat

al

tho

ug

h t

he

acci

den

tal

intr

a-ar

teri

al in

ject

ion

o

f der

mal

fille

rs is

ap

par

entl

y ra

re, t

he

po

ten

tial

ris

k o

f vas

cula

r em

bo

lizat

ion

sh

ou

ld

be

no

ted,

esp

ecia

lly

wh

en in

ject

ion

into

th

e su

bcu

tis

of t

he

gla

bel

lar

reg

ion

, th

e n

asal

ala

, an

d

the

nas

ola

bia

l fo

lds.

Poo

r

Jham

et

al.

PM:1

9138

600

Cas

e re

po

rts

and

co

mp

reh

ensi

ve

liter

atu

re re

view

Vari

ou

s/G

ener

al

po

pu

lati

on

56

Va

rio

us

Up

per

/lo

wer

lip

, NLF

, ch

eek

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 17

K

im e

t al

. 200

4 PM

:150

5614

8 C

ase

Stu

dy

Ko

rea/

Wo

man

wit

h

Art

eco

ll tr

eatm

ent

for n

eck

wri

nkl

es

1 4

yr

Art

eco

ll N

ot

rep

ort

ed

Fore

ign

gra

nu

lom

a d

ue

to

Art

eco

ll in

ject

ion

tre

ated

w

ith

th

ree

inje

ctio

ns

of

tria

mci

no

lon

e. A

rtec

oll

sho

uld

no

t b

e u

sed

as

an

imp

lan

t m

ater

ial i

n t

hin

an

d c

on

stan

tly

mov

able

sk

in.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Lan

dau

200

8 PM

:183

8020

5 C

ase

Seri

es

Isra

el/f

emal

e p

atie

nts

w

ith

an

ave

rag

e ag

e o

f 52.

3yo

15

6 m

o

Evo

len

ce B

reez

e (p

orc

ine

colla

gen

-der

ived

der

mal

fil

ler)

, 1.4

ml

lip a

nd

nas

ola

bia

l fo

lds

In a

ll p

atie

nts

, a n

atu

ral

loo

k w

as a

chie

ved

an

d

fille

r mat

eria

l co

uld

no

t b

e p

alp

ated

. In

all

case

s, th

e co

smet

ic e

ffec

t w

as

mai

nta

ined

up

to t

he

last

vis

it a

t 6

mo

aft

er

inje

ctio

n.

Poo

r

Lom

bar

di e

t al.

2004

PM

:147

2019

8 R

etro

spec

tive

cas

e se

ries

Fr

ance

/Pat

ien

ts

wit

h A

rtec

oll,

D

erm

aliv

e, N

ew-

Fill,

or L

iqu

id-

Silic

on

e in

du

ced

g

ran

ulo

mas

11

No

t re

po

rted

A

rtec

oll

Der

mal

ive

New

-Fill

Li

qu

id-S

ilico

ne

No

t re

po

rted

N

ew d

erm

al fi

llers

may

re

sult

in n

ew t

ypes

of

gra

nu

lom

as t

hat

will

n

eed

to b

e id

enti

fied

for

med

ico

-leg

al re

aso

ns

Poo

r

Luu

et

al. 2

007

PM:1

7321

875

Ret

rosp

ecti

ve c

ase

seri

es

USA

/pat

ien

ts w

ho

u

nd

erw

ent

lary

ng

op

last

y b

etw

een

199

7 an

d

2006

895

No

t re

po

rted

Z

ypla

st

Para

glo

ttic

co

mp

artm

ent

of t

he

voca

l fo

lds

The

auth

ors

’ fin

d t

hat

p

ercu

tan

eou

s co

llag

en

inje

ctio

n la

ryn

go

pla

sty

is s

afe

in p

atie

nts

tak

ing

w

arfa

rin

. Ho

wev

er, t

he

dec

isio

n to

per

form

su

ch in

ject

ion

s in

an

tico

agu

late

d

pat

ien

ts re

sts

wit

h t

he

ph

ysic

ian

per

form

ing

th

is p

roce

du

re. A

lso,

th

e au

tho

rs’ f

eel i

n t

hei

r ex

per

ien

ce, p

rio

r ski

n

hyp

erse

nsi

tivi

ty te

stin

g is

u

nn

eces

sary

wit

h b

ovin

e cr

oss

-lin

ked

co

llag

en.

Poo

r

Mo

od

y et

al.

2000

PM

:110

5049

7 R

etro

spec

tive

cas

e re

po

rt

US/

54 y

r old

wh

ite

wo

man

1

2 m

o

1 cc

Der

mal

og

en (h

um

an

colla

gen

) 30

-gau

ge

nee

dle

test

in

ject

ion

in v

ola

r fo

rear

m

The

liter

atu

re s

ug

ges

ts t

hat

w

hile

hu

man

co

llag

en is

q

uit

e sa

fe, t

he

po

ssib

ility

st

ill e

xist

s fo

r ad

vers

e re

acti

on

.

Poo

r

Mo

od

y et

al.

2001

PM

:115

5316

5 R

etro

spec

tive

cas

e re

po

rt

US/

45 y

r old

wo

man

1

7 w

k Z

yder

m II

(bov

ine

colla

gen

) M

ento

lab

ial c

reas

e,

chin

, lip

s To

pic

al t

acro

limu

s is

a

safe

an

d p

ote

nti

ally

ef

fect

ive

med

icin

e fo

r th

e tr

eatm

ent

of b

ovin

e co

llag

en h

yper

sen

siti

vity

. Th

e au

tho

rs in

dic

ate

furt

her

stu

dy

is re

qu

ired

.

Poo

r


April 2011

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 17

Po

ved

a et

al.

2006

PM

:163

8828

5 R

etro

spec

tive

cas

e se

ries

Sp

ain

/55-

yr-o

ld

wo

man

, 72

year

o

ld w

om

an, 7

0 ye

ar o

ld w

om

an,

54 y

ear o

ld

wo

man

, 43

year

o

ld w

om

an

5 1

mo

B

otu

linu

m to

xin

typ

e A

(B

oto

x) n

=1

Co

llag

en n

=1

Dim

eth

ylp

oly

silo

xan

e (s

ilico

ne)

n=

3

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er li

p,

nas

og

enia

n a

rea,

fa

cial

are

a, c

hee

ks,

chin

, an

d b

ucc

al

mu

cosa

.

The

auth

ors

feel

th

at t

hes

e fil

lers

sh

ou

ld n

ot

be

con

sid

ered

inn

ocu

ou

s. Th

e re

acti

on

to s

ilico

ne

is t

he

mo

st v

iru

len

t, b

ut

adve

rse

reac

tio

ns

hav

e b

een

ob

serv

ed

wit

h p

ract

ical

ly a

ll th

e p

rod

uct

s u

sed

. Th

ey

say

that

mo

re s

tud

ies

are

nec

essa

ry to

stu

dy

oth

er p

oss

ible

bo

dily

re

spo

nse

s to

sili

con

e.

Poo

r

Req

uen

a et

al.

2001

PM

:113

9109

9 R

etro

spec

tive

cas

e se

ries

Sp

ain

/52

yr o

ld m

an,

42 y

r old

wo

man

, 2

38 y

r old

wo

men

4 6-

14 m

o

Art

eco

ll n

=1

Der

mal

ive

n=

1 Si

lico

ne

n=

2

Art

eco

ll: n

aso

lab

ial a

nd

fo

reh

ead

fold

sD

erm

aliv

e: fo

reh

ead

an

d p

erio

cula

r ri

dg

es

Silic

on

e: n

aso

lab

ial

fold

s, ch

eeks

Art

eco

ll an

d D

erm

aliv

e ar

e ab

le to

sti

mu

late

a

clin

ical

ly e

vid

ent

gra

nu

lom

ato

us

reac

tio

n in

rare

cas

es,

even

th

ou

gh

th

ey a

re

com

po

sed

of m

ost

ly

iner

t m

ater

ials

. Sili

con

e,

con

trar

y to

po

pu

lar

op

inio

n, i

s b

enefi

cial

an

d s

afe

wh

en it

is

use

d p

rop

erly

in s

mal

l am

ou

nts

for c

uta

no

ue

soft

tis

sue

Poo

r

Rey

tan

et

al. 2

007

PM:1

7903

163

Cas

e re

po

rt

Ger

man

y/26

yr

old

mal

e w

ith

m

and

ibu

lar

pro

fnat

hia

1 9

wk

Evo

len

ce, 2

.9m

l ove

r 2

sess

ion

s p

hilt

rum

are

a,

verm

illio

n b

ord

er,

and

lip

red

This

cas

e re

po

rt il

lust

rate

s a

pat

ien

t w

ith

man

dib

ula

r p

rog

nat

hia

an

d m

ild

fun

ctio

nal

defi

cits

w

ho

was

ab

le to

hav

e co

rrec

ted

fulln

ess

of

the

up

per

lip

du

e to

co

llag

en fi

ller.

Inje

ctab

le

fille

rs c

ou

ld b

e u

sed

to

aug

men

t o

rom

axill

ofa

cial

su

rger

y w

hen

th

e o

bta

ined

aes

thet

ic

resu

lts

are

no

t as

go

od

as

exp

ecte

d.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Rey

tan

et

al. 2

008

PM:1

9112

805

Pro

spec

tive

cas

e re

po

rt

Ger

man

y/61

yr o

ld

Cau

casi

an H

IV-

po

siti

ve m

ale

pre

sen

ted

wit

h

faci

al li

po

atro

ph

y;

pat

ien

t al

so h

as

his

tory

of H

ep C

1 14

mo

Ev

ole

nce

, 5m

l in

per

iocu

lar

reg

ion

an

d 6

ml i

n c

hee

k au

gm

enta

tio

n to

tal o

ver 4

tr

eatm

ents

chee

k, p

erio

cula

r re

gio

n

The

auth

ors

sta

te t

hat

th

is

case

rep

ort

sh

ow

s th

at

nov

el b

ovin

e co

llag

en

fille

rs o

ffer

an

oth

er

op

tio

n fo

r dec

reas

ing

th

e vi

sib

ility

of f

acia

l lip

oat

rop

hy.

Res

ult

s p

ersi

sted

for 1

4mo

s, al

tho

ug

h fu

rth

er fo

llow

u

p w

ill s

ho

w t

hat

th

e p

atie

nt

req

uir

es re

pea

ted

in

ject

ion

s ov

er t

ime.

A

dd

itio

nal

stu

die

s sh

ou

ld b

e co

nd

uct

ed

to fu

rth

er in

vest

igat

e th

e u

se o

f th

ese

fille

rs

in t

he

trea

tmen

t o

f H

IV- a

sso

ciat

ed fa

cial

lip

oat

rop

hy.

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 17

R

icci

et

al. 2

007

PM:1

8320

835

cas

e se

ries

Ital

y/m

ales

bet

wee

n

43 a

nd

78

yr

old

wit

h s

ever

e d

ysp

hag

ia d

ue

to

par

tial

7 1

yr

Zyp

last

(bov

ine

colla

gen

) L

aryn

go

pla

sty

The

auth

ors

co

ncl

ud

e th

at t

hes

e re

sult

s, ev

en if

refe

rrin

g to

a

smal

l nu

mb

er o

f cas

es,

sho

w t

hat

inje

ctio

n

lary

ng

op

last

y th

rou

gh

fib

er e

nd

osc

op

y ca

n b

e co

nsi

der

ed

a g

oo

d s

olu

tio

n fo

r d

ysp

hag

ia a

fter

par

tial

la

ryn

gec

tom

y. A

lso

th

e vo

ice

can

imp

rove

w

ith

th

is p

roce

du

re.

The

auth

ors

als

o s

tate

th

at it

is w

ort

hw

hile

st

ress

ing

th

at lo

go

pae

dic

re

hab

ilita

tio

n is

fu

nd

amen

tal i

n o

rder

to

stre

ng

then

th

e re

sult

s o

f su

rgic

al t

reat

men

t o

f d

ysp

hag

ia.

Poo

r


April 2011

CaH

A F

iller

s

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

No

. of

stu

die

s, 3

M

oer

s-C

arp

i et

al.

2007

PM

:180

8605

2

Mu

ltic

ente

r, b

lind

ed,

ran

do

miz

ed t

rial

Eu

rop

e/En

rolle

d

pat

ien

ts h

ad

mo

der

ate

or

seve

re N

LFs

205

(192

) 4,

8, 1

2 m

o

Rad

iess

e (C

aHA

), 2.

21 m

l to

tal v

olu

me

(n=

70)

Juvé

der

m 2

4 (H

A-1

A),

4.78

m

l to

tal v

olu

me

(n=

33)

Juvé

der

m 2

4HV

(HA

-1B

), 2.

94

ml t

ota

l vo

lum

e (n

=33

)

Perl

ane

(HA

-2),

2.89

ml t

ota

l vo

lum

e (n

=65

)

Pati

ents

tre

ated

w

ith

eit

her

CaH

A

gel

or H

A fo

r th

e co

rrec

tio

n o

f bo

th

NLF

s. N

earl

y al

l p

atie

nts

(n=

189)

re

ceiv

ed a

tou

ch-u

p

trea

tmen

t at

4 m

o.

Bo

th C

aHA

gel

an

d

the

HA

pro

du

cts

dis

pla

y ad

equ

ate

and

co

mp

arab

le

safe

ty p

rofil

es. I

n t

his

co

ntr

olle

d s

tud

y, C

aHA

g

el ra

nke

d h

igh

est

in

pat

ien

t sa

tisf

acti

on

an

d

likel

iho

od

to re

turn

. Th

e m

ater

ial w

as m

ore

ef

fect

ive

and

lon

ger

la

stin

g t

han

eac

h H

A

in m

ain

tain

ing

NLF

au

gm

enta

tio

n. T

he

auth

ors

bel

ieve

CaH

A

gel

off

ers

adva

nta

ges

in

du

rab

ility

, pat

ien

t sa

tisf

acti

on

, an

d c

ost

, fo

r sa

fe c

orr

ecti

on

of N

LFs.

Go

od

Mo

ers-

Car

pi e

t al

. 20

08

PM:1

8093

199

Mu

ltic

ente

r, p

rosp

ecti

ve,

ran

do

miz

ed,

con

tro

lled,

sp

lit-

face

tri

al

Pati

ents

ser

ved

as

thei

r ow

n c

on

tro

l.

Ger

man

y &

Sp

ain

/M

od

erat

e to

se

vere

NLF

s (3

or 4

o

n W

SRS)

60 (5

8)

6, 9

, 12

mo

R

adie

sse

Res

tyla

ne

Volu

me

req

uir

ed fo

r co

rrec

tio

n in

CaH

A

trea

ted

fold

was

30%

le

ss t

han

th

e vo

lum

e o

f N

ASH

A

Pati

ents

rece

ived

tw

o

inje

ctio

ns

3 m

o

apar

t. A

t th

e in

itia

l vi

sit,

pat

ien

t w

as

trea

ted

wit

h C

aHA

to

co

rrec

t o

ne

NLF

an

d N

ASH

A

to c

orr

ect

the

oth

er N

LF. A

t th

e 3

mo

vis

it, p

atie

nts

re

ceiv

ed a

tou

ch-

up

tre

atm

ent

in

bo

th fo

lds.

CaH

A w

as fo

un

d to

be

sig

nifi

can

tly

mo

re

effe

ctiv

e th

an N

ASH

A.

At

all t

ime

po

ints

, CaH

A

dem

on

stra

ted

lon

ger

la

stin

g re

sult

s an

d

gre

ater

imp

rove

men

t th

an N

ASH

A.

Go

od


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Smit

h e

t al

.200

7PM

:180

8604

8R

and

om

ized

, ev

alu

ato

r-b

lind

ed, b

ilate

ral,

pro

spec

tive

co

mp

aris

on

USA

/Po

ten

tial

su

bje

cts

wer

e re

qu

ired

to

hav

e sy

mm

etri

c,

mo

der

atet

o- d

eep

N

LFs

117

(113

)1,

3, 6

mo

Rad

iess

e (C

olla

gen

)

Co

smo

pla

st (C

aHA

)

Each

sid

e w

as

trea

ted

un

til,

in

the

jud

gm

ent

of

the

inve

stig

ato

r, an

op

tim

al re

sult

w

as a

chie

ved

. At

2 w

k fo

llow

ing

tr

eatm

ent,

sub

ject

s co

uld

rece

ive

tou

ch-u

p in

ject

ion

s at

th

e d

iscr

etio

n

of t

he

ph

ysic

ian

O

ccu

rred

at

2 w

k in

terv

als,

max

imu

m

of t

wo

ad

dit

ion

al

trea

tmen

t se

ssio

ns.

Qu

alify

ing

su

bje

cts

rece

ived

CaH

A

pro

du

ct o

n o

ne

sid

e, a

nd

th

e H

C

pro

du

ct o

n t

he

oth

er.

The

CaH

A-b

ased

pro

du

ct

giv

es s

ign

ifica

ntl

y lo

ng

er la

stin

g c

orr

ecti

on

o

f NLF

s co

mp

ared

to

hu

man

co

llag

en. F

ewer

in

ject

ion

s an

d le

ss to

tal

mat

eria

l are

req

uir

ed. T

he

adve

rse

even

t p

rofil

es o

f th

e tw

o fi

llers

are

sim

ilar.

Go

od

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

15

Bec

ker 2

008

PM:1

8520

907

Un

con

tro

lled

clin

ical

tr

ial

USA

/Gen

eral

p

op

ula

tio

n

24 (1

8)

2-48

mo

R

adie

sse,

0.2

5 to

1.3

ml a

t in

itia

l in

ject

ion

Va

rio

us

loca

tio

ns,

nu

mb

ers

of

inje

ctio

ns

Ch

eek

In s

om

e p

atie

nt,

the

du

rati

on

of

aug

men

tati

on

ext

end

ed

to 2

6 m

o. O

n a

vera

ge,

th

e le

ng

th o

f co

rrec

tio

n

was

9 m

o, a

nd

tou

ch-u

p

pro

ced

ure

s av

erag

ed

6 m

o a

fter

th

e in

itia

l in

ject

ion

an

d re

qu

irin

g a

sm

alle

r vo

lum

e.

Poo

r

Bee

r et

al. 2

008

PM:1

8459

517

Un

con

tro

lled

clin

ical

tr

ial

USA

/Fem

ales

wit

h

sig

ns

of m

id-f

ace

volu

me

loss

19 (1

6)

1, 3

, 6 m

o

Rad

iess

e, v

olu

me

at

dis

cret

ion

of p

hys

icia

n

Tou

ch-u

p t

reat

men

ts

wer

e ad

min

iste

red

at

1 m

o a

t d

iscr

etio

n o

f p

hys

icia

n

Bas

ed o

n t

his

stu

dy

and

ad

dit

ion

al e

xper

ien

ce

wit

h C

aHA

inje

ctio

n, i

t is

bel

ieve

d t

hat

th

e fil

ler

off

ers

a sa

fe, r

easo

nab

le

and

rep

rod

uci

ble

al

tern

ativ

e to

inva

sive

fa

cial

reju

ven

atio

n

Poo

r


April 2011

Ber

lin e

t al

. 200

8PM

:185

4718

4U

nco

ntr

olle

d c

linic

al

tria

lU

SA/S

ub

ject

s w

ith

p

rom

inen

t n

aso

lab

ial r

hyt

ids

56

mo

Rad

iess

e, 0

.1 to

0.2

ml

Rig

ht

po

stau

ricu

lar

area

Soft

tis

sues

au

gm

enta

tio

n

wit

h C

aHA

fille

rs le

ads

to

the

lon

g-t

erm

dep

osi

tio

n

of n

ew c

olla

gen

su

rro

un

din

g fi

ller

mic

rosp

her

es. T

his

may

co

ntr

ibu

te to

th

e ov

eral

l im

pro

vem

ent

in t

he

app

eara

nce

of t

reat

ed

rhyt

ids.

Poo

r

Car

ruth

ers

et a

l. 20

08

PM:1

8547

186

Op

en-l

abel

, si

ng

le- c

ente

r u

nco

ntr

olle

d

clin

ical

tri

al

USA

/Pat

ien

ts w

ith

lip

oat

rop

hy

or

pro

no

un

ced

NLF

s

58

No

ne

Rad

iess

e N

ot

rep

ort

ed

Earl

ier c

linic

al t

rial

s es

tab

lish

ed C

aHA

as

a sa

fe a

nd

eff

ecti

ve s

oft

ti

ssu

e fil

ler.

This

CaH

A

stu

dy

sho

ws

no

ove

rt

rad

iog

rap

hic

saf

ety

con

cern

s. C

aHA

is

un

likel

y to

be

con

fuse

d

wit

h c

onv

enti

on

al

and

ab

no

rmal

an

d

adve

rse

rad

iog

rap

hic

fin

din

gs.

This

pro

du

ct

is n

ot

alw

ays

visi

ble

on

X

-ray

. Alt

ho

ug

h u

sual

ly

visi

ble

on

CT

scan

s, it

s ap

pea

ran

ce is

dis

tin

ct

fro

m t

he

surr

ou

nd

ing

b

on

y st

ruct

ure

s an

d d

oes

n

ot

inte

rfer

e w

ith

no

rmal

an

alys

is. T

he

pro

du

ct

also

do

es n

ot

ob

scu

re

un

der

lyin

g s

tru

ctu

res

on

C

T sc

ans.

Poo

r

Jaco

vella

et

al. 2

006

PM:1

6936

540

Clin

ical

Tri

al

Arg

enti

na/

faci

al

inje

ctio

ns

for

cosm

etic

pu

rpo

ses

40 (4

0)

18 m

o

Rad

iess

e 0.

5-2.

0 m

l (av

erag

e o

f 0.7

5 m

l) In

ject

ion

s to

th

e g

lab

ella

r wri

nkl

es,

nas

ola

bia

l fo

lds,

lips,

no

se, a

nd

/or

infr

aorb

ital

are

a

Rad

iess

e is

hig

hly

eff

ecti

ve

and

lon

g la

stin

g w

ith

h

igh

pat

ien

t sa

tisf

acti

on

fo

r vo

lum

etri

c au

gm

enta

tio

n.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

15

Jan

sen

et

al. 2

006

PM:1

6936

541

Clin

ical

Tri

al

US/

faci

al in

ject

ion

s fo

r co

smet

ic

pu

rpo

ses

609

(155

; 6 m

o)

(112

; 12-

24

mo

) 6,

12-

24 m

o

Rad

iess

e N

aso

lab

ial f

old

s 0.

62 m

l eac

h

n=

395

area

s U

pp

er li

p 0

.6 m

l Lo

wer

lip

0.2

5 m

l n

=33

8 ar

eas

(co

mb

ined

lip

s)

Rad

ial l

ip li

ne

0.25

ml p

er li

ne

n=

163

area

s C

orn

er o

f mo

uth

0.2

8 m

l n

=12

5 ar

eas

Mar

ion

ette

lin

es 0

.49

ml

each

sid

e n

=75

are

as

Gla

bel

lar l

ines

0.2

2 m

l n=

10

6 ar

eas

Ch

in/c

hee

k lin

es 0

.20

ml

n=

50 a

reas

A

cne

scar

s 0.

12 m

l n=

33

area

s Sc

ar d

efo

rmit

ies

0.2-

0.4

ml

n=

21 a

reas

Fa

cial

dep

ress

ion

(HIV

lip

oat

rop

hy)

5.2

5 m

l n=

14

area

s C

hee

k au

gm

enta

tio

n 0

.85

ml

each

sid

e n

=14

are

as

Nas

al d

epre

ssio

ns

0.2

ml n

=6

area

s Te

ar tr

ough

s 0.

35 m

l n=

8 ar

eas

Tou

ch-u

ps

aver

age

0.3

ml

Inje

ctio

ns

to t

he

nas

ola

bia

l fo

lds,

mar

ion

ette

lin

es,

ora

l co

mm

issu

re,

chee

ks, c

hin

, lip

s, an

d/o

r rad

ial l

ip

lines

The

imp

lan

t is

saf

e, lo

ng

la

stin

g, a

nd

hig

hly

ef

fect

ive

Poo

r

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

15

Mar

mu

r et

al. 2

009

PM:1

9708

875

Un

con

tro

lled

clin

ical

tr

ial

USA

/fem

ale

pat

ien

ts

aged

60-

80yo

w

ith

so

ft t

issu

e d

efici

ency

of t

he

do

rsa

of t

he

han

ds

5 24

wks

R

adie

sse,

1.3

ml p

er h

and

for

n=

4 p

atie

nts

an

d 2

.6m

l p

er h

and

for n

=1

pat

ien

t

do

rsal

sid

e o

f han

d

To t

he

auth

ors

’ kn

ow

led

ge,

th

is is

th

e fir

st IR

B a

pp

rove

d

stu

dy

per

form

ed to

d

emo

nst

rate

th

e cl

inic

al

resu

lts

of C

aHA

for s

oft

ti

ssu

e au

gm

enta

tio

n

in t

he

han

ds.

Clin

ical

im

pro

vem

ent

was

st

ill s

een

aft

er 2

4wks

af

ter i

nje

ctio

n. P

atie

nt

sati

sfac

tio

n w

as h

igh

af

ter i

nit

ial i

nje

ctio

n a

nd

re

mai

ned

so

th

rou

gh

th

e

Poo

r


April 2011

Mar

mu

r et

al. 2

009

PM:1

9708

876

No

nra

nd

om

ized

cl

inic

al t

rial

U

SA/p

atie

nts

ag

ed 1

8 yr

an

d o

lder

wit

h

Fitz

pat

rick

ski

n

typ

es IV

to V

I

100

6mo

R

adie

sse,

0.6

-2.8

ml

faci

al w

rin

kles

an

d

fold

s, in

clu

din

g

nas

ola

bia

l fo

lds

The

auth

ors

’ sta

te t

hat

th

e d

ata

sho

w t

hat

p

eop

le w

ith

dar

k sk

in,

if in

ject

ed s

ub

der

mal

ly

wit

h C

aHA

, do

no

t sh

ow

sig

ns

of k

elo

id

form

atio

n, h

yper

tro

ph

ic

scar

rin

g, o

r hyp

er-o

r h

ypo

pig

men

tati

on

. B

ecau

se o

f th

is s

afet

y fe

atu

re, a

s w

ell a

s o

ther

ch

arac

teri

stic

s o

f th

e p

rod

uct

alr

ead

y sh

ow

n in

cl

inic

al li

tera

ture

, CaH

A is

an

att

ract

ive

der

mal

fille

r in

th

is p

op

ula

tio

n.

Poo

r

O’H

ara

et a

l. 20

06

PM:1

6651

970

Clin

ical

Tri

al

US/

pat

ien

ts

un

der

go

ing

zy

go

mat

ic

aug

men

tati

on

8 (8

) 1,

7 d

3, 6

, 12

mo

H

ydro

xyap

atit

e in

ject

ion

s in

0.

5-1.

0cc

incr

emen

ts fr

om

2.

0cc

to 4

.0 c

c p

er s

ide

(ave

rag

e 2.

5cc)

Tran

sco

nju

nct

ival

in

ject

ion

s in

to t

he

sub

per

iost

eal m

alar

p

ock

ets

Inje

ctio

n o

f hyd

roxy

apat

ite

gra

nu

les

thro

ug

h

a tr

ansc

on

jun

ctiv

al

app

roac

h in

to t

he

sub

per

iost

eal m

alar

p

ock

ets

resu

lts

in m

easu

reab

le

aug

men

tati

on

wit

h

min

imal

co

mp

licat

ion

s an

d h

igh

pat

ien

t sa

tisf

acti

on

.

Poo

r

Roy

et

al. 2

006

PM:1

6970

693

Un

con

tro

lled

clin

ical

tr

ial

USA

/pat

ien

ts

req

ues

tin

g

faci

al s

oft

tis

sue

aug

men

tati

on

, n

=3

mal

es a

nd

n

=79

fem

ales

82

3-6

mo

R

adie

sse

The

mea

n a

mo

un

t o

f m

ater

ial i

nje

cted

at

th

e in

itia

l vis

it

was

0.2

9ml i

n t

he

mel

ola

bia

l fo

ld (p

er

sid

e), 0

.34m

l in

th

e u

pp

er li

p, 0

.37m

l in

th

e lo

wer

lip

, an

d 0

.12m

l in

th

e in

frac

om

mis

sura

l fo

ld

The

auth

ors

’ pri

mar

y ex

per

ien

ce w

ith

Rad

iess

e is

ver

y p

osi

tive

, an

d t

hey

d

eter

min

e it

is a

saf

e,

easy

to u

se, p

red

icta

ble

, an

d re

liab

le im

pla

nt

for f

acia

l so

ft t

issu

e au

gm

enta

tio

n.

Poo

r

The

mea

n a

mo

un

t o

f m

ater

ial i

nje

cted

d

uri

ng

tou

ch-u

p

inje

ctio

ns

was

0.

15m

l in

th

e m

elo

lab

ial f

old

s (p

er s

ide)

, 0.1

3ml

in t

he

up

per

lip

, an

d 0

.12m

l in

th

e lo

wer

lip


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Un

con

tro

lled

Clin

ical

Tri

al N

um

ber

of s

tud

ies:

15

Sad

ick

et a

l. 20

07

PM:1

8086

049

Two

sit

e, o

pen

- lab

el

stu

dy

USA

/Su

bje

cts

wit

h fa

cial

so

ft

tiss

ue

defi

cien

cy

amen

able

to

trea

tmen

t

113

6 m

o

Rad

iess

e; 1

.0 m

l (n

=10

2), 2

.0

ml (

n=

12)

Mo

st c

om

mo

nly

tr

eate

d s

ite

was

th

e N

LF (n

=86

). O

ther

sit

es in

clu

ded

p

erio

ral l

ines

, acn

e sc

ars,

tear

tro

ug

h

dep

ress

ion

s, an

d

pre

jow

l su

lcu

s.

In t

he

stu

dy,

CaH

A

per

form

ed w

ell a

nd

ex

hib

ited

a fa

vora

ble

sa

fety

pro

file

alo

ng

wit

h

hig

h p

atie

nts

sat

isfa

ctio

n

and

go

od

du

rab

ility

.

Poo

r

75 (6

7%) h

ad a

sin

gle

in

ject

ion

ses

sio

n; 3

8 (3

4%) h

ad m

ult

iple

se

ssio

ns.

Silv

ers

et a

l. 20

06

PM:1

6936

543

Clin

ical

Tri

al

US/

pat

ien

ts w

ith

fa

cial

lip

oat

rop

hy

seco

nd

ary

to H

IV

100

(100

) 3,

6, 1

2, 1

8 m

o

Rad

iess

e 4.

8 m

l (av

g)

Inje

ctio

ns

to t

he

chee

k ar

ea (s

ub

mal

ar)

per

form

ed b

y th

e in

vest

igat

ors

.

Rad

iess

e is

an

ap

pro

pri

ate

and

wel

l- to

lera

ted

tr

eatm

ent

for p

atie

nts

w

ith

faci

al li

po

atro

ph

y.

Poo

r

Init

ial i

nje

ctio

ns

follo

wed

up

w

ith

su

bse

qu

ent

inje

ctio

ns

at 1

, 6,

and

18

mo

U

nco

ntr

olle

d C

linic

al T

rial

Nu

mb

er o

f stu

die

s: 15

Sk

lar e

t al

. 200

4 PM

:150

9932

2 C

linic

al T

rial

U

S/p

atie

nts

wit

h

sub

cuta

neo

us

or

dee

p t

issu

e at

rop

y

64 (6

4)

6 m

o

Rad

ian

ce F

N

Nas

ola

bia

l fo

lds

0.91

ml (

avg

) 0.

4-2.

0 m

l n

=52

Te

ar t

rou

gh

0.3

5

ml (

avg

) 0.3

-0.7

ml

n=

15

Lip

s 0.

67 m

l (av

g) 0

.2-1

.4 m

l n

=15

In

frao

ral 0

.29

ml (

avg

) 0.1

-0.5

m

l n=

11

Ch

eeks

0.6

0 m

l (av

g) 0

.3- 1

.2

ml n

=4

Men

tal c

reas

e 0.

15 m

l (av

g)

0.1-

0.2

ml n

=2

Ab

ove

up

per

lip

0.2

0 m

l (a

vg) 0

.2 m

l n=

1 B

ucc

al re

gio

n 2

.0 m

l (av

g) 2

.9

ml n

=1

Inje

ctio

ns

in a

re

tro

gra

de

tech

niq

ue

to

Nas

ola

bia

l fo

lds,

Tear

tro

ug

h, L

ips,

Infr

aora

l, C

hee

ks,

Men

tal c

reas

e,

Ab

ove

up

per

lip

, B

ucc

al re

gio

n

Rad

ian

ce F

N c

an b

e u

sed

as

a d

eep

so

ft t

issu

e fil

ler

wit

h im

med

iate

aes

thet

ic

effe

ct a

nd

litt

le d

ow

n-

tim

e

Poo

r


April 2011

Stu

pak

et

al. 2

007

PM:1

7372

068

Pro

spec

tive

, bef

ore

-an

d-a

fter

, clin

ical

tr

ial

USA

/pat

ien

ts w

ith

p

ost

-rh

ino

pla

sty

con

tou

r ir

reg

ula

riti

es o

r as

ymm

etry

13

2.5

mo

R

adie

sse,

mea

n d

ose

was

0.

19m

l D

ors

um

an

d b

ilate

ral

wal

ls o

f th

e n

asal

re

gio

n

Cal

ciu

m h

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ite

has

b

een

sh

ow

n in

th

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tud

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resu

lt in

imp

rove

men

t in

po

st-r

hin

op

last

y n

asal

sym

met

ry a

nd

in

sm

oo

thin

g o

f th

e cu

rves

an

d li

nes

th

at

con

stit

ute

th

e co

nto

ur o

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e n

ose

. Ove

rall,

pat

ien

t sa

tisf

acti

on

was

hig

h

and

few

pro

ble

ms

wer

e en

cou

nte

red

. Lo

ng

-ter

m

stu

die

s o

f saf

ety

and

ef

ficac

y ar

e w

arra

nte

d.

Poo

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Un

con

tro

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Clin

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al N

um

ber

of s

tud

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15

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as 2

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Clin

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US/

pat

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so

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6 m

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ian

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N 0

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l (av

g)

Inje

ctio

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ub

der

mal

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bet

wee

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su

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tan

eou

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th

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aso

lab

ial

fold

s, g

lab

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ario

net

te

lines

, pre

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epre

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acn

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and

su

rgic

al

soft

tis

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def

ects

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Rad

ian

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N is

eff

ecti

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w

ell-

tole

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d.

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Inje

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th

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th

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lan

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mu

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14

6 m

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Rad

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ean

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init

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surg

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nas

al

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30

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req

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dit

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uch

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at 2

wk

follo

w-

up

vis

it

All

pat

ien

ts to

lera

ted

th

e p

roce

du

re w

ell,

and

on

ly

on

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req

ues

ted

a

min

or t

ou

ch-u

p a

t 2

wk.

A

t th

e 6

mo

follo

w-u

p,

cosm

etic

resu

lts

and

p

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nt

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PM:1

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188

Ret

rosp

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revi

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USA

/Pat

ien

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18 y

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so

ft

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defi

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amen

able

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1000

1

yr

Rad

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ean

vo

lum

e 1.

9 m

l Va

riet

y fa

cial

co

nto

uri

ng

ap

plic

atio

ns,

maj

ori

ty N

LFs

and

m

ario

net

te li

nes

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

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pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

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sio

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Gra

de

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al S

tud

y N

um

ber

of s

tud

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1 A

lam

et

al. 2

007

PM:1

7224

371

Pro

spec

tive

follo

w-

up

stu

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USA

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ts

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sen

ted

for

corr

ecti

on

of

dep

ress

ion

s o

f th

e n

aso

lab

ial f

old

s

22 (1

8)

1-1.

5yr

Rad

iess

e, 1

-2m

l in

eac

h N

LF

Nas

ola

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l fo

lds

Wh

en a

co

nsi

sten

t, d

efin

ed

inje

ctio

n te

chn

iqu

e is

u

sed,

inje

ctab

le c

alci

um

h

ydro

xyla

pat

ite

app

ears

to

be

a w

ell-

tole

rate

d

soft

-tis

sue

aug

men

tati

on

m

ater

ial f

or c

orr

ecti

on

o

f nas

ola

bia

l fo

ld

dep

ress

ion

s. A

lon

g

du

rati

on

of e

ffec

t m

ay

mak

e th

is m

ater

ial

par

ticu

larl

y d

esir

able

for

som

e p

atie

nts

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Poo

r

Cas

e Se

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/Rep

ort

Nu

mb

er o

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die

s: 11

B

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007

PM:1

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619

Cas

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po

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USA

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6 w

k R

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3.9

ml

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ola

bia

l cre

ases

an

d

mar

ion

ette

lin

es

In t

his

cas

e, a

dis

tan

t n

od

ule

is

do

cum

ente

d fo

llow

ing

in

ject

ion

s o

f Rad

iess

e.

Alt

ho

ug

h t

he

pro

du

ct

is s

afe

and

eff

ecti

ve fo

r co

smet

ic in

dic

atio

ns,

on

e sh

ou

ld b

e aw

are

of t

he

po

ten

tial

for t

his

or a

ny

fille

r to

mig

rate

an

d b

e p

rep

ared

to d

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th

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qu

ence

s.

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ase

Seri

es

US/

Pati

ents

wit

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hyp

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lic

sub

cuta

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lesi

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d a

h

isto

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f fac

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5 (5

) N

A

Rad

iess

e 1.

Inje

ctio

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to t

he

left

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azyg

om

atic

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gio

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2. In

ject

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s to

th

e in

frao

rbit

al a

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in

fraz

ygo

mat

ic

reg

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Inje

ctio

ns

to t

he

infr

aorb

ital

an

d

infr

azyg

om

atic

re

gio

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4. In

ject

ion

s to

th

e in

frao

rbit

al,

nas

ola

bia

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aro

tid

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d p

erio

ral r

egio

ns

5. In

ject

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s to

th

e in

frao

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infr

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d

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l

CaH

a d

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ller i

s h

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nu

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g o

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o

n F

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o

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term

edia

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ign

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nd

is a

p

ote

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ause

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Poo

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April 2011

Go

din

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PM:1

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Pro

spec

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Cas

e Se

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US/

pat

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101

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10 m

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old

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pp

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p

verm

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ord

ers,

“lip

stic

k lin

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p

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Co

mb

inat

ion

gro

up

te

nd

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hav

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reat

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inte

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d o

vera

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tisf

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sco

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than

th

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:159

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Ret

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Seri

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Nu

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K

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us

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l. 20

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rep

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1 6

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Rad

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o 1

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gio

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auth

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pre

sen

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or p

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ass

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om

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nas

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auth

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ve t

hey

hav

e p

rese

nte

d t

he

first

cas

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po

rt d

escr

ibin

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ad

vers

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acti

on

an

d t

he

trea

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r th

is p

rob

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e au

tho

rs b

elie

ve t

hat

p

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a m

etic

ulo

us

inje

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an

d a

void

ance

o

f ove

r- in

ject

ion

w

ill h

elp

pre

ven

t th

is

com

plic

atio

n.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

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de

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tho

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ca

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un

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th

at

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cosm

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fille

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fo

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me

mo

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om

mo

n, d

enti

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sho

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qu

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on

pat

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abo

ut

any

cosm

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p

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they

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un

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p

earl

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d

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ell

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bel

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lines

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The

auth

ors

sta

te t

hat

to

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led

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is t

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first

des

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of t

he

fille

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du

cin

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ap

pea

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kin

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th

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ith

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Poo

r


April 2011

Cas

e Se

ries

/Rep

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Nu

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Ret

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w

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ing

up

to 2

yea

rs.

The

tech

niq

ue

sho

wn

in

this

stu

dy

pro

vid

es a

n

easy

, sem

iper

man

ent,

safe

ap

pro

ach

to s

mal

l sk

ull

def

ects

th

at c

an b

e p

erfo

rmed

in a

n o

ffice

o

r am

bu

lato

ry s

urg

ery

sett

ing.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

PL

LA

Fill

ers

Sys

tem

atic

Rev

iew

: No

. of

stu

die

s, 1

El

-Bey

rou

ty e

t al

. 20

06

PM:1

6912

248

Syst

emat

ic R

evie

w

US,

En

gla

nd

an

d

Fran

ce/

syst

emat

ic

revi

ew o

f stu

die

s co

nd

uct

ed in

H

IV li

po

atro

ph

y p

op

ula

tio

ns

of

wh

ite

mal

es

6 cl

inic

al t

rial

s: V

EGA

Ch

else

a an

d W

estm

in-

ster

Laf

auti

e et

al.

APE

X 0

01

APE

X 0

02

Blu

e Pa

cific

Vari

ou

s Po

ly-L

-lac

tic

acid

1.

VEG

A: P

oly

-L-l

acti

c ac

id 4

.0

ml n

=47

2.

Ch

else

a an

d W

estm

inst

er:

Poly

-L-l

acti

c ac

id 3

.0 m

l n

=29

3.

Laf

auti

e et

al.:

Po

ly-L

- lac

tic

acid

2.5

ml n

=94

4.

APE

X 0

01: P

oly

-L-l

acti

c ac

id

1.0-

8.0

ml n

= 1

00

5. A

PEX

002

: Po

ly-L

-lac

tic

acid

8.

0 m

l n=

99

6. B

lue

Paci

fic G

rou

p: P

oly

-L-

lact

ic a

cid

6.0

ml n

=99

Inje

ctio

ns

to t

he

chee

ks fo

r th

e tr

eatm

ent

of H

IV

lipo

atro

ph

y

Poly

-L-l

acti

c ac

id o

ffer

s a

trea

tmen

t al

tern

ativ

e fo

r pat

ien

ts w

ith

HIV

- as

soci

ated

lip

oat

rop

y in

w

hit

e

Poo

r

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

No

. of

stu

die

s, 2

M

oyle

et

al. 2

004

PM:1

5012

646

RC

TU

K/P

atie

nts

wit

h

HIV

ind

uce

d f

acia

l lip

oat

rop

hy

30 (3

0)0,

12,

24

wk

New

-Fill

imm

edia

te

trea

tmen

t n

=15

New

-Fill

del

ayed

tre

atm

ent

n=

15

Inje

ctio

n in

to t

he

dee

p

der

mis

ove

rlyi

ng

th

e b

ucc

al fa

t p

ad

PLA

inje

ctio

ns

led

to

imp

rove

men

ts in

pat

ien

t se

lf p

erce

pti

on

an

d

dec

reas

ed a

nxi

ety

and

d

epre

ssio

n s

core

s

Go

od

PL

LA

Fill

ers

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

No

. of

stu

die

s, 2

M

oyle

et

al.2

006

PM:1

6494

632

RC

TU

S/Pa

tien

ts w

ith

H

IVre

late

d fa

cial

lip

oat

rop

hy

30 (2

7)18

mo

Scu

lptr

a (P

LLA

) im

med

iate

tr

eatm

ent

3.0

ml n

=15

Scu

lptr

a (P

LLA

) del

ayed

tr

eatm

ent

3.0

ml n

=15

Thre

e se

ts o

f bila

tera

l in

ject

ion

s, 2

wee

ks

apar

t, to

th

e d

eep

d

erm

is a

bov

e th

e b

ucc

al fa

t p

ad

PLLA

has

a fa

vora

ble

lon

g-

term

saf

ety

and

effi

cacy

p

rofil

e

Go

od

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f st

ud

ies,

4

Bee

r 200

7 PM

:180

8605

4 Si

ng

le-c

ente

r, o

pen

-la

bel

stu

dy

USA

/Su

bje

cts

wit

h fa

cial

sca

rs

resu

ltin

g fr

om

m

od

erat

e to

se

vere

acn

e o

r va

rice

lla

20 (1

6)

At

each

tre

atm

ent

sess

ion

Sc

ulp

tra

Inje

ctio

ns

wer

e g

iven

at

1 m

o in

terv

als

to

pri

mar

y en

dp

oin

t o

f re

solu

tio

n o

f sca

rs

(up

to 7

tre

atm

ent)

Inje

ctab

le P

LLA

as

use

d in

th

is in

vest

igat

ion

ap

pea

rs

to c

orr

ect

the

typ

es o

f ac

ne

scar

s tr

eate

d in

th

is

stu

dy

wit

ho

ut

the

seri

ou

s si

de

effe

cts.

Trea

tmen

t 6

and

7 d

ata

sug

ges

t th

at

red

uct

ion

s in

siz

e an

d

seve

rity

may

pla

teau

af

ter T

reat

men

t 6.

Poo

r


April 2011

Bu

rges

s et

al.

2005

PM

:156

9246

7 C

linic

al T

rial

U

S/H

IV-i

nfe

cted

m

ales

on

HA

AR

T w

ith

faci

al

lipo

atro

ph

y

61

6, 1

8 m

o

New

-Fill

St

age

I lip

oat

rop

hy

4.0-

12.

0 cc

n=

9 St

age

II lip

oat

rop

hy

8.0-

12.

0 cc

n=

15

Stag

e III

lip

oat

rop

hy

12.0

- 24

.0 c

c n

=30

St

age

IV li

po

atro

ph

y 16

.0-

24.0

cc n

=7

Inje

ctio

n to

th

e ju

nct

ion

of t

he

sub

cuta

neo

us-

dee

p d

erm

al p

lan

e.

Fan

nin

g in

ject

ion

te

chn

iqu

e w

as u

sed

to

cre

ate

a d

eep

d

erm

al la

ttic

e

Use

of P

LA to

tre

at fa

cial

lip

oat

rop

hy

resu

lted

in

sig

nifi

can

t an

d

pro

lon

ged

imp

rove

men

t in

tre

ated

pat

ien

ts u

p to

tw

o y

ears

Poo

r

Han

ke e

t al

. 200

7 PM

:173

7316

9 U

nco

ntr

olle

d c

linic

al

tria

l U

SA/2

7 H

IV p

osi

tive

p

aten

ts a

nd

38

HIV

n

egat

ive

pat

ien

ts

65

2 yr

Sc

ulp

tra,

4-8

ml

chee

ks

PLLA

is a

n in

ject

able

fille

r th

at c

orr

ects

so

ft-t

issu

e vo

lum

e lo

ss s

eco

nd

ary

to H

IV li

po

atro

ph

y an

d li

po

atro

ph

y o

f ag

ing.

Tre

atm

ent

is

safe

an

d e

ffec

tive

in

bo

th H

IV p

osi

tive

an

d

HIV

neg

ativ

e p

atie

nts

. Pr

ecis

e te

chn

iqu

e is

es

sen

tial

for g

oo

d re

sult

s. R

esu

lts

are

lon

g la

stin

g

and

ass

oci

ated

wit

h

hig

h ra

tes

of p

atie

nt

sati

sfac

tio

n.

Poo

r

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f st

ud

ies,

4

Salle

s et

al.

2008

PM:1

8551

341

Un

con

tro

lled

clin

ical

tr

ial

Bra

zil/

Gen

eral

p

op

ula

tio

n10

6, 3

6 m

oSc

ulp

tra

NLF

s, O

ne

inje

ctio

n p

er

mo

for 3

mo.

Rat

ien

ts n

eed

to b

e co

un

sele

d a

bo

ut

the

del

ayed

pro

cess

of

aest

het

ic t

ran

sfo

rmat

ion

. Th

e re

sult

s sh

ow

ed t

hat

at

3 y

, th

e PL

A fi

ller w

as

stab

le. T

he

aug

men

tati

on

re

sult

s w

ith

PLA

fille

r co

uld

last

up

to 3

yr.

Poo

r

Co

ho

rt S

tud

y N

um

ber

of s

tud

ies:

7 K

avo

un

i et

al. 2

008

PM:1

8449

827

Ret

rosp

ecti

ve

anal

ysis

of P

LLA

tr

eatm

ent

UK

/HIV

-po

siti

ve

pat

ien

ts w

ith

faci

al

lipo

atro

ph

y

441

3-32

mo

N

ew-F

ill

Min

imu

m 1

0 m

l in

ject

ed in

to fa

cial

ar

eas

incl

ud

ing

th

e te

mp

les,

infr

aorb

ital

g

roov

es, b

ucc

al

area

s, n

aso

lab

ial

fold

s, ab

ove

and

b

elo

w t

he

zyg

om

a an

d p

rep

aro

tid

The

char

acte

rist

ics

of t

he

trea

tmen

t p

roto

col t

hat

al

low

ed fo

r an

incr

ease

in

the

per

ceiv

ed re

solu

tio

n

of f

acia

l ch

ang

es to

90%

in

clu

ded

usi

ng

tw

o v

ials

p

er s

essi

on

(on

e vi

al p

er

each

sid

e o

f th

e fa

ce),

a si

gn

ifica

nt

exp

ansi

on

of

the

faci

al a

reas

tre

ated

, an

d a

n in

crea

se in

th

e n

um

ber

of s

essi

on

s b

ased

on

lip

oat

rop

hy

seve

rity

.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Levy

et

al. 2

008

PM:1

9022

099

Pro

spec

tive

co

ho

rt

stu

dy

USA

/HIV

po

siti

ve

and

HIV

neg

ativ

e p

atie

nts

65 (5

3)3

yrSc

ulp

tra,

5.0

mL

Hal

f of t

he

volu

me

inje

cted

into

d

erm

is, h

alf i

nto

th

e u

nd

erly

ing

su

bcu

tan

eou

s ti

ssu

e; 4

to 8

are

as

on

eac

h c

hee

k

PLLA

is a

saf

e an

d e

ffec

tive

tr

eatm

ent

to c

orr

ect

HIV

lip

oat

rop

hy

and

lip

oat

rop

hy

of a

gai

n.

Res

ult

s ap

pea

r to

be

lon

g

last

ing,

per

sist

ing

for u

p

to 3

yea

rs w

ith

ad

dit

ion

al

trea

tmen

t in

a s

ub

set

of p

atie

nts

an

d a

nd

at

leas

t 1

year

aft

er t

he

last

tre

atm

ent.

Pati

ent

sati

sfac

tio

n w

ith

PLL

A

is h

igh

.

Poo

r

Low

e et

al.

2009

PM:1

9207

324

Sin

gle

-cen

ter,

retr

osp

ecti

ve

surv

ey

UK

/Pat

ien

ts

rece

ivin

g 1

-5 P

LLA

tr

eatm

ents

221

6 to

24

mo

Scu

lptr

aC

hee

ks, p

erio

ral,

chin

, d

elto

ids,

thig

hs,

glu

teal

, fo

reh

ead

Inje

ctab

le P

LLA

pro

vid

es

an o

pti

on

for c

orr

ecti

ng

ar

eas

of v

olu

me

loss

. Se

vera

l tre

atm

ent

sess

ion

s ar

e re

qu

ired

to

ob

tain

max

imu

m

ben

efits

, wh

ich

may

be

a p

ract

ical

pro

ble

m fo

r p

atie

nts

. Th

e ef

ficac

y an

d s

afet

y is

en

han

ced

b

y u

sin

g a

n o

pti

miz

ed

inje

ctio

n te

chn

iqu

e an

d

app

rop

riat

e p

ost

inje

ctio

n

care

, in

clu

din

g m

assa

ge.

Poo

r

Maz

zuco

et

al. 2

009

PM:1

9438

668

Pro

spec

tive

, n

on

com

par

ativ

e st

ud

y

Bra

zil/

Pati

ents

wit

h

on

e o

r mo

re o

f th

e fo

llow

ing

sig

ns

of

agin

g: c

uta

neo

us

flacc

idit

y, a

tro

ph

y,

and

wri

nkl

es in

th

e n

eck

and

ch

est

36

60 d

, 18

mo

A

vera

ge

3.9

ml d

ose

inje

cted

p

er s

essi

on

n=

36

Nec

k an

d c

hes

t (p

rest

ern

al a

rea)

; av

erag

e 1.

8 se

ssio

ns

per

pat

ien

t

The

use

of P

LLA

in t

he

nec

k an

d c

hes

t w

as

safe

an

d e

ffica

cio

us

and

re

pre

sen

ts a

pro

ph

ylac

tic

and

th

erap

euti

c al

tern

ativ

e fo

r th

e tr

eatm

ent

of fl

acci

dit

y an

d li

po

atro

ph

y o

f th

ese

diffi

cult

are

as, w

ith

low

er

risk

an

d m

orb

idit

y th

an

conv

enti

on

al s

urg

ical

Poo

r


April 2011

Co

ho

rt S

tud

y N

um

ber

of s

tud

ies,

7 M

est

et a

l. 20

09

PM:1

9207

325

Sin

gle

-sit

e, o

pen

- la

bel

, ret

reat

men

t st

ud

y in

itia

ted

af

ter t

he

12- m

on

th,

trea

tmen

t- fr

ee,

follo

w-u

p p

has

e o

f th

e B

lue

Paci

fic

stu

dy.

USA

/HIV

-po

siti

ve

pat

ien

ts

65

24 m

o

PLLA

, 1-1

0 m

l Pa

tien

ts t

reat

ed a

t 5-

wee

k in

terv

als

un

til f

ull

corr

ecti

on

w

as o

bta

ined

.

Inje

ctab

le P

LLA

is a

saf

e an

d e

ffec

tive

lon

g-t

erm

tr

eatm

ent

op

tio

n fo

r HIV

- as

soci

ated

lip

oat

rop

hy.

Poo

r

Neg

red

o e

t al

. 200

6 PM

:171

9214

8 C

om

par

ativ

e,

pro

spec

tive

co

ho

rt s

tud

y

Spai

n/

HIV

-in

fect

ed

pat

ien

ts

pre

sen

tin

g w

ith

an

tire

trov

iral

- as

soci

ated

faci

al

lipo

atro

ph

y fo

r m

ore

th

an 6

mo

s

138

(n=

8 re

ceiv

ed

fat,

n=

25

rece

ived

po

ly-L

- la

ctic

aci

d, a

nd

n

=10

5 re

ceiv

ed

po

lyac

ryla

mid

g

el)

96 w

k A

nal

og

ou

s fa

t o

bta

ined

by

lipo

suct

ion

, 50m

l Po

lyla

ctic

Aci

d, 3

-14m

l Po

lyac

ryla

mid

gel

, 4-1

8ml

Nas

ola

bia

l fo

lds

The

auth

ors

’ co

ncl

ud

e th

at p

oly

acry

lam

ide

gel

pro

vid

es t

he

lon

ges

t la

stin

g re

sult

s o

f th

e th

ree

pro

du

cts

com

par

ed. H

ow

ever

, b

iod

egra

dab

le p

rod

uct

s, su

ch a

s fa

t an

d

po

lyla

ctic

aci

d s

ho

uld

al

so b

e co

nsi

der

ed

as v

iab

le o

pti

on

s fo

r th

e tr

eatm

ent

of f

acia

l lip

oat

rop

hy.

Th

e ch

oic

e o

f th

e b

est

pro

du

ct fo

r re

con

stru

ctiv

e p

urp

ose

s sh

ou

ld b

e m

ade

in

con

cord

ance

wit

h a

p

hys

icia

n’s

clin

ical

ev

alu

atio

n a

nd

th

e p

atie

nt’s

pre

fere

nce

s.

Fair

Sad

ick

et a

l. 20

08

PM:1

9016

062

Ret

rosp

ecti

ve

coh

ort

U

SA/G

ener

al

po

pu

lati

on

26

6-

12 m

o

PLLA

, 1.5

-2.0

ml

Han

d, m

ean

2.3

8 tr

eatm

ents

per

p

atie

nt

The

over

all r

esu

lts

fro

m t

he

thre

e cl

inic

s p

rese

nte

d

sho

w t

hat

pat

ien

ts w

ere

very

sat

isfie

d w

ith

th

e re

sult

s o

f PLL

A t

reat

men

t fo

r th

e h

and

s, an

d

exp

erie

nce

d o

nly

min

or

and

sh

ort

-ter

m in

ject

ion

-re

late

d a

nd

rela

ted

ev

ents

.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

19

Ap

ikia

n e

t al

. 200

7 PM

:175

2412

5 R

etro

spec

tive

cas

e se

ries

A

ust

ralia

/4 w

hit

e w

om

en a

ged

48

-57

4 7

d -

2 yr

N

ew-F

ill

Rep

ort

1: i

nfr

aorb

ital

ar

eas,

tem

po

ral

area

s, ch

eek

area

The

use

of N

ewFi

ll in

th

e in

frao

rbit

al re

gio

n s

ho

uld

b

e av

oid

ed u

nti

l mo

re

stu

die

s ar

e co

mp

lete

d.

Poo

r

Rep

ort

2: e

ach

in

frao

rbit

al re

gio

n

and

nas

ola

bia

l lin

e R

epo

rt 3

: in

frao

rbit

al

area

, nas

oju

gal

lin

es,

mar

ion

ette

lin

es

in fi

rst

trea

tmen

t, in

frao

rbit

al a

rea,

ch

eek

bo

ne

area

, an

d m

ario

net

te

lines

6 w

eeks

alt

er.

Rep

ort

4: i

nfr

aorb

ital

ar

eas,

chee

ks, a

nd

m

ario

net

te li

nes

. B

eer 2

009

PM:1

9207

333

Pro

spec

tive

Cas

e R

epo

rt

US/

64 y

r old

w

om

an c

osm

etic

tr

eatm

ent

of

per

iorb

ital

are

as,

59-y

r- o

ld w

om

an

eval

uat

ed fo

r fac

ial

reju

ven

atio

n

US/

59-y

ear-

old

w

om

an t

reat

men

t o

f mid

-fac

e d

esce

nt

2 (2

) 12

-18

mo

PL

LA, 2

.0 m

l eac

h te

ar

tro

ug

h, t

wo

ses

sio

ns,

4 w

ks a

par

t PL

LA, 1

.0 m

l, ea

ch te

ar

tro

ug

h

Dep

ot

inje

ctio

ns

into

ea

ch te

ar t

rou

gh

m

ade

at t

he

leve

l of

the

per

iost

eum

Inje

ctio

ns

into

th

e ch

eeks

, tea

r tro

ug

hs,

and

zyg

om

atic

arc

h

area

s

The

auth

ors

co

ncl

ud

e th

at

del

ayed

form

atio

n o

f p

apu

les

in t

he

per

iorb

ital

ar

ea w

ere

pre

sen

ted

by

the

pat

ien

t.Th

e au

tho

rs

also

su

gg

est

that

clin

ical

tr

ials

in t

his

are

a m

ay

pro

vid

e m

ore

insi

gh

t in

to t

he

etio

log

y an

d

trea

tmen

t to

imp

rove

th

e o

utc

om

es a

sso

ciat

ed

wit

h P

LLA

.

Poo

r

Bel

jaar

ds

et a

l. 20

05

PM:1

6029

705

Ret

rosp

ecti

ve c

ase

rep

ort

Th

e N

eth

erla

nd

s/3

wo

men

ag

ed

35-5

3

3 12

-22

mo

1-

3 m

l rec

on

stit

ute

d N

ewFi

ll (p

oly

lact

ic a

cid

) N

aso

lab

ial f

old

s, ch

eeks

, lip

s, n

eck.

Ph

ysic

ian

s sh

ou

ld b

e ap

pre

hen

sive

ab

ou

t u

sin

g N

ewFi

ll. B

ecau

se

ther

e ar

e n

o te

sts

avai

lab

le to

ind

icat

e w

ho

m

ay b

e su

scep

tib

le to

th

e o

bse

rved

sid

e ef

fect

s, th

e au

tho

rs s

ug

ges

t th

at t

he

use

of f

ore

ign

b

od

y m

ater

ials

for t

issu

e au

gm

enta

tio

n is

ris

ky.

Poo

r


April 2011

Bu

rges

s 20

08

PM:1

8231

700

Cas

e re

po

rt

USA

/ 69

yr o

ld

Afr

ican

-Am

eric

an

wo

man

1 18

mo

s Sc

ulp

tra,

5m

l eac

h t

reat

men

t, tw

o t

reat

men

ts to

tal

der

mal

su

bcu

tan

eou

s p

lan

e o

f th

e u

pp

er

and

low

er c

hee

ks

as w

ell a

s th

e p

reau

ricu

lar a

nd

m

alar

reg

ion

s

The

auth

ors

co

ncl

ud

e th

at t

he

use

of P

LLA

re

pre

sen

ts a

wel

l-to

lera

ted

an

d e

ffec

tive

m

inim

ally

inva

sive

tr

eatm

ent

for f

acia

l co

nto

ur d

efec

ts c

ause

d

by

lipo

atro

ph

y.

Poo

r

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

19

Ham

ilto

n e

t al

. 200

8 PM

:180

5303

1 C

ase

rep

ort

Fr

ance

/58

yr o

ld

imm

un

o -

com

pet

ent

fem

ale

pre

sen

ted

wit

h

sub

cuta

neo

us

no

du

les

1 4

yr

Scu

lptr

a, 9

ml

Nas

ola

bia

l fo

lds

(6m

l) C

uta

neo

us

bo

rder

of

the

verm

ilio

n (1

ml)

Jug

om

alar

dep

ress

ion

ad

jace

nt

to

the

infr

aorb

ital

p

erio

steu

m (2

ml)

The

auth

ors

bel

ieve

th

at

inad

vert

ent

pla

cem

ent

of P

LA in

th

e u

pp

er

der

mis

or t

he

clu

mp

ing

o

f im

pla

nt

bea

ds

in t

he

dee

per

tis

sue

pla

nes

is a

co

mm

on

cau

se o

f ear

ly-

on

set

no

du

les.

It is

th

e ex

per

ien

ce o

f th

e au

tho

rs

that

hig

her

dilu

tio

ns

of

PLA

ap

pea

r to

yie

ld lo

wer

in

cid

ence

of l

ate-

on

set,

infla

mm

ato

ry n

od

ule

s.

Poo

r

Jham

et

al.

PM:1

9138

600

Cas

e re

po

rts

and

co

mp

reh

ensi

ve

liter

atu

re re

view

Vari

ou

s/G

ener

al

po

pu

lati

on

56

Va

rio

us

Up

per

/lo

wer

lip

, NLF

, ch

eek

Poo

r

Kat

es e

t al

. 200

8PM

:190

8355

2C

ase

rep

ort

USA

/ 2

wh

ite

mal

es

in t

hei

r 40s

wit

h

faci

al li

po

atro

ph

y w

ho

had

bee

n

HIV

-po

siti

ve fo

r m

ore

th

an 1

0yrs

212

mo

PLLA

dee

p d

erm

is o

r su

bcu

tan

eou

s la

yer o

f th

e fa

ce, 2

vi

als

in e

ach

of 5

tr

eatm

ents

sp

aced

4

wks

ap

art

As

dem

on

stra

ted

wit

h

thes

e ca

ses,

PLLA

is

an e

xcel

len

t ch

oce

for

vlu

me

reto

rati

on

in t

he

HIV

-ass

oci

ated

faci

al

lipo

atro

ph

y p

atie

nt

wit

h

lon

g-l

asti

ng

resu

lts.

Poo

r

Lom

bar

di e

t al.

2004

PM

:147

2019

8 R

etro

spec

tive

cas

e se

ries

Fr

ance

/Pat

ien

ts

wit

h A

rtec

oll,

D

erm

aliv

e, N

ew-

Fill,

or L

iqu

id-

Silic

on

e in

du

ced

g

ran

ulo

mas

11

No

t re

po

rted

A

rtec

oll

Der

mal

ive

New

-Fill

Li

qu

id-S

ilico

ne

No

t re

po

rted

N

ew d

erm

al fi

llers

may

re

sult

in n

ew t

ypes

of

gra

nu

lom

as t

hat

will

n

eed

to b

e id

enti

fied

for

med

ico

-leg

al re

aso

ns

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Mes

t et

al.

2006

PM

:170

8358

5 Pr

osp

ecti

ve c

ase

seri

es

USA

/pat

ien

ts o

ver

the

age

of 1

8 w

ith

H

IV s

ero

po

siti

vity

an

d fa

cial

lip

oat

rop

hy

97(7

5)

12 m

o

PLLA

, 1-6

ml p

er s

essi

on

, w

ith

pat

ien

ts re

ceiv

ing

b

etw

een

1 a

nd

6 s

essi

on

s

chee

ks a

nd

tem

ple

s Th

e re

sult

s o

f th

is s

tud

y cl

earl

y sh

ow

th

e lo

ng

-ter

m (1

2mo

) ef

fect

iven

ess

of

inje

ctab

le P

LLA

in

the

trea

tmen

t o

f H

IV-a

sso

ciat

ed fa

cial

lip

oat

rop

hy.

Th

e fin

din

gs

of t

his

stu

dy

also

rein

forc

e p

revi

ou

s Eu

rop

ean

stu

die

s th

at

PLLA

is a

saf

e an

d

effe

ctiv

e tr

eatm

ent

for

HIV

- ass

oci

ated

faci

al

lipo

atro

ph

y.

Poo

r

Pove

da

et a

l. 20

06

PM:1

6388

285

Ret

rosp

ecti

ve c

ase

seri

es

Spai

n/5

5-yr

-old

w

om

an, 7

2 ye

ar

old

wo

man

, 70

year

old

wo

man

, 54

yea

r old

w

om

an, 4

3 ye

ar

old

wo

man

5 1

mo

B

otu

linu

m to

xin

typ

e A

(B

oto

x) n

=1

Co

llag

en n

=1

Dim

eth

ylp

oly

silo

xan

e (s

ilico

ne)

n=

3

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er li

p,

nas

og

enia

n a

rea,

fa

cial

are

a, c

hee

ks,

chin

, an

d b

ucc

al

mu

cosa

.

The

auth

ors

feel

th

at t

hes

e fil

lers

sh

ou

ld n

ot

be

con

sid

ered

inn

ocu

ou

s. Th

e re

acti

on

to s

ilico

ne

is t

he

mo

st v

iru

len

t, b

ut

adve

rse

reac

tio

ns

hav

e b

een

ob

serv

ed

wit

h p

ract

ical

ly a

ll th

e p

rod

uct

s u

sed

. Th

ey

say

that

mo

re s

tud

ies

are

nec

essa

ry to

stu

dy

oth

er p

oss

ible

bo

dily

re

spo

nse

s to

sili

con

e.

Poo

r

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

19

Ral

sto

n e

t al

. 200

6 PM

:173

7315

1 R

etro

spec

tive

cas

e re

po

rt

US/

40 y

r old

wh

ite

wo

man

1

10 m

o

Scu

lptr

a U

pp

er a

rm

Mel

ano

ma

pat

ien

t h

ad

sig

nifi

can

t im

pro

vem

ent

fro

m o

ne

trea

tmen

t w

ith

Sc

ulp

tra.

Th

is e

xper

ien

ce

sug

ges

ts t

hat

th

is

pro

du

ct m

ay b

e ab

le to

b

e u

sed

for t

reat

men

t af

ter e

xcis

ion

al s

urg

ery.

Poo

r


April 2011

Red

aelli

200

6 PM

:171

7774

5 C

ase

seri

es

Ital

y/fe

mal

e p

atie

nts

ag

ed b

etw

een

59

-72

27

6-15

mo

PL

LA, 2

ml p

er h

and

in t

he

first

ses

sio

n, 1

-2m

l fo

r su

bse

qu

ent

sess

ion

s

do

rsu

m o

f th

e h

and

Po

lyla

ctic

aci

d c

an t

reat

th

e p

rob

lem

of h

and

ae

sth

etic

s w

ith

a g

oo

d

chan

ce o

f su

cces

s. Th

e ex

per

ien

ce is

sti

ll sm

all

and

mu

st b

e va

lidat

ed

over

th

e ye

ars.

Ab

ove

all,

the

real

ab

sen

ces

of m

ajo

r sid

e ef

fect

s m

ust

be

con

firm

ed

wit

h lo

ng

er fo

llow

-up

, ai

min

g in

par

ticu

lar t

o

avo

id n

od

ule

s. In

th

e au

tho

r’s o

pin

ion

th

e p

rin

cip

al s

ide

effe

cts,

no

du

les,

are

ascr

ibab

le

to a

n u

nsa

tisf

acto

ry

tech

niq

ue.

On

e ca

nn

ot

forg

et t

hat

at

leas

t 1.

5 h

rs w

ith

an

esth

esia

an

d

mas

sag

e is

th

e re

qu

ired

ti

me

for t

his

pro

ced

ure

. In

ord

er to

ob

tain

go

od

re

sult

s, it

is m

and

ato

ry to

h

ave

this

tim

e av

aila

ble

to

co

mp

lete

all

the

step

s w

ith

du

e ca

re.

Poo

r

Ren

do

n e

t al

. 200

8 PM

:184

4184

3 Pr

osp

ecti

ve c

ase

rep

ort

U

SA/6

4 yr

old

wo

man

w

ho

un

der

wen

t ex

ten

sive

su

rgic

al

pro

ced

ure

s fo

r d

amag

e to

th

e cr

anio

faci

al a

rea

follo

win

g a

car

ac

cid

ent

1 5

mo

Po

ly-L

-lac

tic

Aci

d, 5

ml

Dee

p d

erm

is o

f th

e ch

eeks

(2m

l);

nas

ola

bia

l fo

lds

(1m

l), z

ygo

mat

ic

arch

es (1

ml),

tem

ps

(0.5

ml),

an

d c

hin

(0

.5m

l) A

bov

e tr

eatm

ent

rep

eate

d 2

mo

re

tim

es a

bo

ut

a m

on

th a

par

t

The

auth

ors

sta

te t

hat

th

is

case

rep

ort

dem

on

stra

tes

that

PLL

A c

an b

e u

sed

for c

orr

ecti

on

of

faci

al li

pat

rop

hy

and

as

ymm

etry

sec

on

dar

y to

tra

um

atic

inju

ry. P

LLA

sh

ou

ld b

e co

nsi

der

ed in

th

e tr

eatm

ent

of t

rau

ma

ind

uce

d fa

cial

lip

otr

aph

y an

d a

sym

met

ry a

nd

may

h

ave

a fu

ture

role

in t

he

trea

tmen

t o

f co

ng

enti

al

abn

orm

alit

ies

as w

ell.

Poo

r

Res

zko

et

al. 2

009

PM:1

9207

329

Ret

rosp

ecti

ve C

ase

Rep

ort

U

S/62

yr o

ld

imm

un

o -

com

pet

ent

pat

ien

t

1 (1

) 12

-18

mo

sin

ce

trea

tmen

t Sc

ulp

tra

(Po

ly-L

-lat

ic a

cid

) B

ilate

ral c

hee

ks, c

hin

, an

d in

frao

rbit

al

area

s

Wh

ile fo

reig

n b

od

y g

ran

ulo

mas

are

a

rep

ort

ed s

ide

effe

ct

fro

m P

LA in

ject

ion

, wit

h

app

rop

riat

e d

epo

siti

on

te

chn

iqu

e an

d a

deq

uat

e d

iluti

on

, th

is a

dve

rse

even

t ca

n b

e ra

re.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

19

Ro

ssn

er e

t al

. 200

9 PM

:192

5016

0 C

ase

seri

es

Ger

man

y/Pa

tien

ts fr

om

B

erlin

Reg

istr

y p

rese

nti

ng

an

ad

vers

e re

acti

on

to

PLA

22

8 yr

N

ew-F

ill

No

t re

po

rted

PL

A is

an

inje

ctab

le fi

ller

sub

stan

ce t

hat

in

mo

st c

ases

of a

dve

rse

even

ts p

rod

uce

d

sub

cuta

neo

us

no

du

les.

As

the

freq

uen

cy o

f th

e re

po

rted

reac

tio

ns

was

follo

wed

ove

r a

per

iod

of 8

yr,

the

dat

a su

gg

est

a p

osi

tive

in

fluen

ce o

f hig

her

d

iluti

on

of P

LA to

war

ds

a d

ecre

ased

ris

k o

f no

du

le

form

atio

n. T

her

efo

re, a

h

igh

er d

iluti

on

sh

ou

ld

be

reco

mm

end

ed to

p

hys

icia

ns

usi

ng

PLA

.

Poo

r

Sch

ulm

an e

t al

. 20

08

PM:1

8186

871

Cas

e re

po

rt

USA

/63

yr o

ld t

hin

fe

mal

e w

ho

co

mp

lain

ed o

f a

sup

erio

r “st

ep-

off

def

orm

ity

and

vis

ible

in

terc

ost

al s

pac

es

afte

r im

pla

nt

reco

nst

ruct

ion

1 9

mo

Sc

ulp

tra

- 4 t

reat

men

ts a

t 1

mo

nth

inte

rval

s, ea

ch

trea

tmen

t w

as t

wo

36

7.5m

g v

ials

Sub

cuta

neo

us

tiss

ue

and

dee

p d

erm

a la

yers

of t

he

sup

erio

r an

d m

edia

l ri

gh

t ch

est

wal

l

The

auth

ors

sta

te t

hat

th

ey h

ave

pre

sen

ted

a

succ

essf

ul c

ase

of t

he

use

of S

culp

tra

in t

he

corr

ecti

on

of a

per

sist

ent

ches

t w

all d

efec

t af

ter

imp

act

reco

nst

ruct

ion

in

an

ext

rem

ely

thin

w

om

an.

Poo

r

Stew

art

et a

l. 20

07

PM:1

7667

102

Cas

e re

po

rt

USA

/39

yr o

ld fe

mal

e p

rese

nte

d w

ith

m

ult

iple

vis

ible

, p

alp

able

pap

ule

s in

bila

tera

l in

frao

rbit

al re

gio

n

1 4

mo

Sc

ulp

tra

bila

tera

l in

frao

rbit

al

reg

ion

In

the

case

of P

LLA

, pro

per

re

con

stit

utio

n o

f th

e p

rod

uct a

pp

ears

to p

lay

a si

gn

ifica

nt ro

le in

rate

s of

n

odul

e fo

rmat

ion

. Sh

ould

a

sym

pto

mat

ic g

ran

ulom

a fo

rm in

the

per

iorb

ital

ar

ea, c

urre

ntly

the

mos

t ef

fect

ive

trea

tmen

t wou

ld

be

a m

inim

ally

inva

sive

su

rgic

al

Poo

r

Wo

erle

et

al. 2

004

PM:1

5303

782

Pro

spec

tive

cas

e se

ries

an

d

retr

osp

ecti

ve

case

rep

ort

Euro

pe/

300

pat

ien

ts

(70%

m) f

or

pro

spec

tive

, 48

yr

old

man

an

d 5

1 yr

old

wo

man

for

retr

o

302

12-2

4 m

o

Poly

-L-l

acti

c ac

id

26 g

aug

e n

eed

le in

to

the

nas

ola

bia

l fo

lds,

Mar

ion

ette

lin

es,

lab

iom

enta

l cre

ases

, u

pp

er li

p, c

hee

ks,

chin

, an

d te

mp

les.

The

auth

ors

dee

m p

oly

-L-

lact

ic a

cid

eff

ecti

ve

for w

inkl

es, f

old

s, an

d

dep

ress

ion

s o

f th

e lo

wer

fa

ce.

Poo

r


April 2011

Fro

m 1

999-

2002

th

e ac

id m

ixtu

re s

too

d

for 2

-12

ho

urs

b

efo

re in

ject

ion

. A

fter

war

ds

the

mix

ture

sto

od

for

36-4

8 h

ou

rs.

Wo

lfram

et

al. 2

006

PM:1

7135

735

Ret

rosp

ecti

ve c

ase

seri

es

Au

stri

a/2

58 y

r old

w

om

en, 1

53

yr o

ld

wo

man

3 3

mo

- 2

yr

New

fill,

Res

tyla

ne,

Der

maL

ive

Zyg

om

atic

arc

h,

eyel

ids,

fore

hea

d,

nas

ola

bia

l fo

lds,

chee

ks

Giv

en t

he

incr

easi

ng

use

o

f fille

rs, i

t m

igh

t b

e w

ort

h c

on

sid

erin

g

rem

ovin

g t

hem

fro

m

the

list

of m

edic

al it

ems

and

incl

ud

ing

th

em in

a

cate

go

ry w

ith

mo

re

stri

ng

ent

inve

stig

atio

n.

Poo

r

PM

MA

Fill

ers

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

No

. of

stu

die

s, 2

C

oh

en e

t al

. 200

4 PM

:154

6840

6 R

CT

US/

pat

ien

ts a

t le

ast

18 y

ears

of

age

pre

sen

tin

g

for g

lab

ella

r, n

aso

lab

ial f

old

s, ra

dia

l up

per

lip

lin

es, m

ario

net

te

lines

co

rrec

tio

n

251

(251

) (11

1 at

12

1, 3

, 6, 1

2 m

o

Art

eco

ll n

=12

8 Z

yder

m II

or Z

ypla

st n

=12

3 Tu

nn

elin

g te

chn

iqu

e:

lab

ella

, nas

ola

bia

l fo

lds,

rad

ial u

pp

er

lip li

nes

, mar

ion

ette

lin

es

Stu

dy

dem

on

stra

ted

th

e re

lati

ve s

afet

y an

d

effe

ctiv

enes

s o

f Art

eco

ll re

lati

ve to

th

at o

f co

llag

en

Go

od

Co

hen

et

al. 2

006

PM:1

6936

546

RC

T (d

ou

ble

-blin

d)

US/

pat

ien

ts w

ith

w

rin

kles

of t

he

gla

bel

la, n

aso

lab

ial

fold

s, ra

dia

l up

per

lip

lin

es, a

nd

co

rner

s o

f th

e m

ou

th; t

reat

ed

wit

h P

MM

A fi

ller

in p

ivo

tal R

CT

(Co

hen

200

4)

251

(233

) 69

4 to

5

year

) 1,

3, 6

, 12

mo

4-5

ye

ars

Art

eFill

(am

ou

nt

no

t sp

ecifi

ed) n

=12

8 C

olla

gen

(am

ou

nt

no

t sp

ecifi

ed) n

=12

3

Inje

ctio

n a

t th

e g

lab

ella

, nas

ola

bia

l fo

lds,

rad

ial u

pp

er

lip li

nes

, or c

orn

ers

of t

he

mo

uth

Stu

dy

dem

on

stra

ted

th

e ov

eral

l saf

ety

and

ef

fect

iven

ess

of A

rteF

ill

rela

tive

to a

co

llag

en

con

tro

l. Ef

fect

iven

ess

was

dem

on

stra

ted

for a

ll ar

eas

trea

ted

.

Go

od


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Co

ho

rt S

tud

y N

um

ber

of s

tud

ies:

1 C

oh

en e

t al

. 200

7 PM

:180

8606

2 5

yr fo

llow

-up

o

f ori

gin

al

RC

T, s

ub

ject

s ra

nd

om

ized

to

po

lym

eth

yl -

met

ha-

cry

late

(P

MM

A) fi

ller

trea

tmen

t o

r wh

o

elec

ted

to c

ross

ov

er to

PM

MA

fil

ler t

her

apy

at

the

con

clu

sio

n

of 6

mo

co

llag

en

con

tro

l tre

atm

ent

USA

/Pat

ien

ts t

reat

ed

wit

h P

MM

A fi

ller

in p

ivo

tal R

CT

(Co

hen

200

4)

251

(145

) 5

yr

Art

eFill

, 0.8

2 m

l/fo

ld n

=12

8 N

LF

Follo

w-u

p s

tud

y sh

ow

ed

PMM

A fi

ller c

on

tin

ued

to

mai

nta

in s

ign

ifica

nt

cosm

etic

co

rrec

tio

n fo

r 5

yr p

ost

inje

ctio

n. T

his

is

the

on

ly F

DA

ap

pro

ved

fil

ler w

ith

a d

ocu

men

ted

d

ura

bili

ty o

ver a

5 y

r p

erio

d. T

he

pro

du

ct w

as

wel

l to

lera

ted,

an

d it

s sa

fety

was

co

nsi

sten

t w

ith

oth

er s

oft

tis

sue

fille

r ag

ents

. May

als

o

off

er a

dd

itio

nal

saf

ety

ben

efits

bec

ause

few

re

pea

t tr

eatm

ents

are

n

eed

ed.

Poo

r

Cas

e Se

ries

/Rep

ort

Nu

mb

er o

f stu

die

s: 10

Bed

ocs

et

al. 2

008

PM:1

8441

850

Cas

e re

po

rt

USA

/ 19

70 w

om

an

pre

sen

ted

wit

h

a 3m

o h

isto

ry o

f an

ery

them

ato

us

pru

riti

c p

laq

ue

loca

ted

in

the

area

of a

n

un

conv

enti

on

al

invi

sib

le t

atto

o

pla

ced

on

th

e u

pp

er a

rm

1 9

mo

sin

ce

pro

ced

ure

PM

MA

wit

h fl

uo

resc

ent

dye

U

pp

er a

rm

PMM

A is

an

ele

gan

t co

mp

ou

nd

wit

h v

ario

us

form

s an

d fu

nct

ion

s. In

co

ntr

act

to it

s o

ther

m

edic

al u

ses,

PMM

A u

se

in d

erm

ato

log

y h

as b

een

m

et w

ith

resi

stan

ce d

ue

to in

crea

sed

rep

ort

ed

inci

den

ce o

f ad

vers

e ev

ents

. Th

e au

tho

rs

bel

ieve

th

is is

th

e fir

st

rep

ort

ed c

ase

of a

g

ran

ulo

ma

form

atio

n

cau

sed

by

recr

eati

on

al

use

of a

PM

MA

imp

lan

t in

th

e fo

rm o

f an

invi

sib

le

tatt

oo.

Poo

r


April 2011

Car

valh

o, I

et a

l. 20

09

PM:1

9438

669

Pro

spec

tive

cas

e re

po

rt

Bra

zil/

men

an

d

wo

men

wit

ho

ut

pre

vio

us

faci

al

aug

men

tati

on

tr

eatm

ents

, 30%

(n

=79

) wit

h fa

cial

at

rop

hy

du

e to

A

IDS,

60%

(n=

159)

w

ith

ph

oto

agin

g

sig

ns,

9% (n

=5)

w

ith

dep

ress

ed

bu

t d

iste

nsi

ble

sc

ars,

and

1%

(n

=3)

wit

h re

sid

ule

d

epre

ssio

ns

fro

m

cuta

neo

us

lup

us

pro

fou

nd

us

154

fem

ales

11

2 m

ales

1

mo

an

d 6

mo

p

ost

- tre

atm

ent,

and

th

en e

ach

yr

for 9

yrs

Met

acri

ll (P

MM

A),

1ml-

8m

l d

epen

din

g o

n p

atie

nt

24-,

23-,

or 2

6- g

aug

e n

eed

les

use

d,

pro

du

ct in

sert

ed a

t th

e su

bcu

tan

eou

s ti

ssu

e o

r su

bd

erm

al

laye

r

sess

ion

s va

ried

fro

m

1-4,

wit

hin

inte

rval

s o

f ap

pro

xim

atel

y 40

-60

day

s b

etw

een

ap

plic

atio

ns.

Au

tho

rs n

ote

th

at t

hei

r st

ud

y in

dic

ates

PM

MA

to

be

safe

, an

d t

hat

th

ey

ob

serv

ed a

hig

h ra

te

of p

atie

nt

sati

sfac

tio

n,

corr

ob

ora

tin

g p

rod

uct

ef

ficac

y an

d g

oo

d re

sult

s ev

en a

fter

sev

eral

yea

rs

of t

he

pro

ced

ure

. As

a re

sult

of t

his

stu

dy,

th

e au

tho

rs c

on

clu

de

that

PM

MA

use

d fo

r th

e tr

eatm

ent

of a

tro

ph

y,

dep

ress

ion

s, an

d fa

cila

w

rin

kles

has

bee

n

sho

wn

to b

e ef

fect

ive,

lo

ng

-las

tin

g, s

afe,

an

d

gra

tify

ing

to p

atie

nts

an

d

ph

ysic

ian

s.

Poo

r

da

Co

sta

Mig

uel

et

al. 2

009

PM:1

9243

914

Ret

rosp

ecti

ve c

ase

rep

ort

B

razi

l/56

yr o

ld

fem

ale

pre

sen

ted

w

ith

sw

ellin

g in

th

e lo

wer

lip

1 ca

se p

rese

nte

d

1yr f

ollo

win

g

trea

tmen

t

PMM

A

Lip

Th

is c

ase

rep

ort

ale

rts

pro

fess

ion

al to

th

e p

oss

ibili

ty o

f un

usu

al

clin

ical

pre

sen

tati

on

s o

f fo

reig

n b

od

y g

ran

ulo

mas

as

soci

ated

wit

h t

he

inje

ctio

n o

f per

man

ent

cosm

etic

fille

rs.

Poo

r

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

10

Gel

fer e

t al

. 200

7 PM

:174

5158

7 C

ase

Seri

es

Un

ited

Sta

tes/

Gen

eral

p

op

ula

tio

n

10

Up

to 3

y

10 c

ases

pre

sen

ted

. Va

rio

us

site

s Th

e so

ft t

issu

e au

gm

enti

ng

ag

ent A

rtec

oll

has

pro

ven

to

be

a sa

fe, e

ffec

tive

, an

d lo

ng

-las

tin

g

solu

tio

n fo

r der

mal

co

nto

uri

ng

defi

cien

cies

. In

exp

erie

nce

d h

and

s, it

is

ass

oci

ated

wit

h a

ver

y lo

w in

cid

ence

of a

dve

rse

effe

cts.

The

mai

n c

on

cern

ab

ou

t it

s u

se is

rep

ort

s o

f gra

nu

lom

a fo

rmat

ion

as

a la

te c

om

plic

atio

n.

Alt

ho

ug

h t

he

rate

of

gra

nu

lom

a fo

rmat

ion

has

d

ecre

ased

sig

nifi

can

tly

du

e to

pro

du

ct e

volu

tio

n

fro

m A

rtep

last

to A

rtec

oll

to A

rtefi

ll, it

rem

ain

s a

con

cern

th

at n

eed

s to

be

add

ress

ed.

Poo

r


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Jham

et

al.

PM:1

9138

600

Cas

e re

po

rts

and

co

mp

reh

ensi

ve

liter

atu

re re

view

Vari

ou

s/G

ener

al

po

pu

lati

on

56

Va

rio

us

Up

per

/lo

wer

lip

, NLF

, ch

eek

Poo

r

Nel

son

et

al. 2

008

PM:1

8023

267

Ret

rosp

ecti

ve c

ase

seri

es

UK

/ Pa

tien

ts w

ith

H

IV- a

sso

ciat

ed

lipo

dys

tro

ph

y

46 (4

6)

Ran

ged

fro

m 1

-14

mo

C

ole

man

au

tolo

go

us

fat

inje

ctio

n n

=26

N

ewfil

l n=

10

Bio

-Alc

amid

n=

8 Tr

eatm

ent

(e.g

., lip

osu

ctio

n)

for f

at a

ccu

mu

lati

on

New

fill i

nje

ctio

ns

wer

e p

erfo

rmed

b

y a

trai

ned

nu

rse

spec

ialis

t. O

ne

vial

o

f New

fill p

er c

hee

k w

as in

ject

ed to

th

e d

eep

der

mis

o

f aff

ecte

d a

reas

(i.

e., c

hee

k, te

mp

le)

du

rin

g e

ach

tr

eatm

ent

sess

ion

.

Bas

ed o

n t

hei

r exp

erie

nce

, th

e re

sear

cher

s co

ncl

ud

ed t

hat

th

ey

favo

red

th

e u

se o

f au

tolo

go

us

fat

inje

ctio

ns

for f

acia

l lip

oat

rop

hy

bu

t h

ave

fou

nd

fille

rs to

be

use

ful i

n p

atie

nts

wit

h

inad

equ

ate

fat

rese

rves

.

Poo

r

Bio

-alc

amid

inje

ctio

ns

wer

e p

erfo

rmed

in

a t

hea

tre

envi

ron

men

t. Th

e p

rod

uct

was

in

ject

ed u

nti

l to

tal c

orr

ecti

on

o

f th

e d

efici

t w

as

ob

tain

ed.

Para

da

et a

l. 20

05

PM:1

6276

149

His

tolo

gic

p

rep

arat

ion

s fr

om

11

bio

psi

es

colle

cted

ove

r a

two

yea

r per

iod

.

Bra

zil

11

No

t re

po

rted

n

=13

(Res

ult

s n

ot

pro

vid

ed

for t

his

revi

ew)

Res

tyla

ne

(hya

luro

nic

aci

d),

Met

acri

l (p

oly

met

hyl

-m

eth

acry

late

), A

qu

amid

(p

oly

acry

lam

ide)

, New

-Fill

(p

oly

lact

ic a

cid

), A

rtec

oll

(po

lym

eth

ylm

eth

acry

late

su

spen

ded

in a

co

llag

en

solu

tio

n).

Bio

psi

es fi

xed

in 1

0%

form

alin

. Th

e au

tho

rs p

ost

ula

te t

hat

in

crea

sin

g n

um

ber

s o

f “b

izar

re fo

reig

n b

od

y-ty

pe

gra

nu

lom

ato

us

reac

tio

ns

in t

he

ora

l fa

cial

reg

ion

s o

f mid

dle

-ag

ed w

om

en” a

re d

ue

to in

ject

ion

s w

ith

on

e o

r m

ore

of t

hes

e fil

lers

.

Poo

r


April 2011

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

10

Salle

s et

al.

2008

PM

:184

5400

7 R

etro

spec

tive

cas

e se

ries

B

razi

l/ 7

mal

es a

nd

25

fem

ales

wit

h

an a

vera

ge

age

of 4

3.6

325

yr s

ince

tre

atm

ent

Poly

met

hyl

-met

hac

ryla

te

No

se, p

enis

, nas

ola

bia

l fo

ld, g

lute

us,

mal

ar

and

su

bm

alar

re

gio

ns,

abd

om

en,

per

iocu

lar,

fro

nta

l d

epre

ssed

sca

r, fr

on

tal r

egio

n a

nd

ch

in, g

lab

ella

, lip

The

auth

ors

sta

te t

hat

co

mp

ared

to t

he

nu

mb

er

of s

ucc

essf

ul c

ases

of

po

lym

eth

ylm

eth

acry

late

in

ject

ion

s, co

mp

licat

ion

s ar

e ra

re, h

ow

ever

, d

esp

ite

bei

ng

rare

, th

ese

com

plic

atio

ns

wer

e se

vere

, per

man

ent,

and

diffi

cult

or e

ven

im

po

ssib

le to

tre

at. F

or

this

reas

on

, th

e au

tho

rs

stat

e th

at s

om

e sa

fety

g

uid

elin

es s

ho

uld

b

e o

bse

rved

, su

ch a

s av

oid

ing

hig

h v

olu

mes

an

d a

void

ing

intr

ader

mal

an

d in

tram

usc

ula

r in

ject

ion

s. Th

e au

tho

rs

do

no

t ad

vise

inje

ctio

n

in t

he

lips

or i

n t

he

bo

dy

(glu

teu

s o

r pen

is).

Poo

r

Zie

lke

et a

l. 20

08

trea

ted

are

as

in 4

8 PM

:181

7739

9

Cas

e se

ries

Th

e au

tho

r’s d

ata

sup

po

rt p

rio

r tr

eatm

ents

of

der

mafi

llers

wh

o

dev

elo

ped

a

reac

tio

n in

on

e o

r mo

re o

f th

e tr

eate

d a

reas

Ger

man

y/p

atie

nts

w

ith

th

e n

eed

fo

r fem

ales

, n

=1

mal

es);

8 p

atie

nts

wer

e ex

clu

ded

so

th

at n

=48

re

mai

ned

for

furt

her

an

alys

is

56 (

n=5

5 P

oo

r h

yalu

ron

ic a

cid

, an

d

no

n b

iod

egra

dab

le

fille

r, P

MM

A,

po

lyac

ryla

mid

e g

el,

and

po

lyet

hyl

ene

No

t re

po

rted

pat

ien

ts

Nas

ola

bia

l fo

ld (n

=

67),

follo

wed

by

the

lips

(n =

27)

, co

rner

s o

f th

e m

ou

th (n

=

27),

and

gla

bel

la

(n=

16)

Bio

deg

rad

able

fille

r, g

oo

d p

ost

mar

keti

ng

su

rvei

llan

ce t

hat

will

le

ad u

s to

a b

ette

r u

nd

erst

and

ing

of

the

nat

ure

an

d r

isks

o

f in

ject

able

fille

r su

bst

ance

s an

d t

hei

r si

de

effe

cts.

Esp

ecia

lly

no

nb

iod

egra

dab

le

pro

du

cts

hav

e to

be

care

fully

mo

nit

ore

d,

sin

ce t

he

adve

rse

even

ts

asso

ciat

ed w

ith

th

ese

pro

du

cts

are

esp

ecia

lly

diffi

cult

to

167


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Sili

con

e O

il F

iller

s S

yste

mat

ic R

evie

w: N

o. o

f st

ud

ies,

1

Ch

asan

200

7 PM

:180

9077

0 Sy

stem

atic

revi

ew

USA

N

/A

N/A

Si

lico

ne

oil

N/A

In

its

curr

ent u

se, s

ilico

ne

oil

for p

erm

anen

t so

ft ti

ssu

e au

gm

enta

tio

n c

ou

ld

be

a ve

ry p

ower

ful t

oo

l. Th

ere

is s

om

e lit

erat

ure

th

at s

up

po

rts

the

use

of a

sm

all a

mo

un

t of p

uri

fied,

h

igh

vis

cosi

ty s

ilico

ne

oil;

how

ever

, th

ere

has

no

t bee

n a

sin

gle

lo

ng

itu

din

al s

tud

y to

dat

e w

ith

ap

pro

pri

ate

follo

w-

up

dat

a. T

he

un

answ

ered

q

ues

tio

n re

mai

ns:

Are

the

risk

s w

ort

h th

e p

ote

nti

al

ben

efits

of s

ilico

ne

oil

as a

per

man

ent fi

ller?

H

owev

er, t

her

e is

sti

ll a

lack

of l

on

g- t

erm

follo

w-

up

dat

a.

Poo

r

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f st

ud

ies,

1

Jon

es e

t al

. 200

4 PM

:154

5852

3 O

pen

pilo

t tr

ial

Un

ited

Sta

tes

and

C

anad

a/Pa

tien

ts

wit

h s

tab

le, w

ell-

con

tro

lled

HIV

77

N/A

Si

liko

n 1

000

or V

itre

Sil 1

000

n=

77

Ch

eeks

for t

reat

men

t o

f fac

ial l

ipo

atro

ph

y 37

6 to

tal i

nje

ctio

n

amo

ng

77

pat

ien

ts

Pilo

t tr

ial h

as d

emo

nst

rate

d

that

hig

hly

pu

rifie

d 1

000-

cSt

silic

on

e o

il is

a s

afe

and

eff

ecti

ve t

reat

men

t o

pti

on

for h

um

an

imm

un

od

efici

ency

vi

rus

faci

al li

po

atro

ph

y.

Lon

ger

-ter

m s

afet

y an

d e

ffica

cy in

hu

man

im

mu

no

defi

cien

cy v

iru

s p

atie

nts

rem

ain

s to

be

pro

ven

.

Poo

r

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

4

Jaci

nto

200

5 PM

:164

1663

7 R

etro

spec

tive

ca

se s

erie

s P

hili

pp

ines

/p

atie

nts

u

nd

erg

oin

g

206

case

s (1

91

case

s)

NA

S

ilico

ne

Oil

0.5

- 4.

6 m

l In

trad

erm

al

inje

ctio

ns

for

acn

e an

d

po

stva

rice

lla

scar

s

Sili

con

e o

il in

ject

ed w

ith

th

e co

rrec

t in

dic

atio

ns

and

tec

hn

iqu

es a

nd

w

ith

mic

rod

rop

let

inje

ctio

ns

is a

saf

e,

eco

no

mic

al, a

nd

p

erm

anen

t d

erm

al

and

su

bcu

tan

eou

s fi

ller.

Po

or


April 2011

Dee

p d

erm

al

inje

ctio

ns

for

nas

ola

bia

l g

roo

ves,

g

lab

ella

r fr

ow

n

lines

, in

fram

alar

cr

ease

s an

d

dep

ress

ion

s,

mar

ion

ette

lin

es,

and

sle

ep li

nes

S

ilico

ne

Oil

Fill

ers

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

4

Para

da

et a

l. 20

05

PM:1

6276

149

His

tolo

gic

p

rep

arat

ion

s fr

om

11

bio

psi

es

colle

cted

ove

r a

two

yea

r p

erio

d.

Bra

zil

11

No

t re

po

rted

R

esta

lyn

e (h

yalu

ron

ic

acid

), M

etac

ril

(po

lym

eth

yl -

met

hac

ryla

te),

A

qu

amid

(p

oly

acry

lam

ide)

, N

ew-F

ill (

po

lyla

ctic

ac

id),

A

rtec

oll

(po

lym

eth

yl-

met

hac

ryla

te

susp

end

ed in

a

colla

gen

so

luti

on

).

Bio

psi

es fi

xed

in

10%

fo

rmal

in.

Th

e au

tho

rs p

ost

ula

te

that

incr

easi

ng

n

um

ber

s o

f “b

izar

re

fore

ign

bo

dy-

typ

e g

ran

ulo

mat

ou

s re

acti

on

s in

th

e o

ral

faci

al r

egio

ns

of

mid

dle

-ag

ed w

om

en”

are

du

e to

inje

ctio

ns

wit

h o

ne

or

mo

re o

f th

ese

fille

rs.

Po

or

Pove

da

et a

l. 20

06

PM:1

6388

285

Ret

rosp

ecti

ve

case

ser

ies

Sp

ain

/55-

yr-o

ld

wo

man

, 72

year

o

ld w

om

an,

70 y

ear

old

w

om

an, 5

4 ye

ar

old

wo

man

, 43

year

old

wo

man

5 1

mo

B

otu

linu

m t

oxi

n t

ype

A

(Bo

tox)

n=1

C

olla

gen

n=1

D

imet

hyl

po

lysi

loxa

ne

(sili

con

e) n

=3

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er

lip, n

aso

gen

ian

ar

ea, f

acia

l are

a,

chee

ks, c

hin

, an

d

bu

ccal

mu

cosa

.

Th

e au

tho

rs f

eel t

hat

th

ese

fille

rs s

ho

uld

n

ot

be

con

sid

ered

in

no

cuo

us.

Th

e re

acti

on

to

sili

con

e is

th

e m

ost

vir

ule

nt,

b

ut

adve

rse

reac

tio

ns

hav

e b

een

ob

serv

ed

wit

h p

ract

ical

ly a

ll th

e p

rod

uct

s u

sed

. Th

ey

say

that

mo

re s

tud

ies

are

nec

essa

ry t

o s

tud

y o

ther

po

ssib

le b

od

ily

resp

on

ses

to s

ilico

ne.

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Req

uen

a et

al.

2001

PM

:113

9109

9 R

etro

spec

tive

ca

se s

erie

s S

pai

n/5

2 yr

old

m

an, 4

2 yr

old

w

om

an, 2

38

yr

old

wo

men

4.6-

14 m

o

Art

eco

ll n

=1

Der

mal

ive

n=1

S

ilico

ne

n=2

Art

eco

ll: n

aso

lab

ial

and

fo

reh

ead

fo

lds

Der

mal

ive:

fo

reh

ead

an

d

per

iocu

lar

rid

ges

S

ilico

ne:

nas

ola

bia

l fo

lds,

ch

eeks

Art

eco

ll an

d D

erm

aliv

e ar

e ab

le t

o s

tim

ula

te

a cl

inic

ally

evi

den

t g

ran

ulo

mat

ou

s re

acti

on

in r

are

case

s, e

ven

th

ou

gh

th

ey a

re c

om

po

sed

o

f m

ost

ly in

ert

mat

eria

ls. S

ilico

ne,

co

ntr

ary

to p

op

ula

r o

pin

ion

, is

ben

efici

al

and

saf

e w

hen

it

is u

sed

pro

per

ly in

sm

all a

mo

un

ts f

or

cuta

neo

us

soft

tis

sue

Po

or

Oth

er F

iller

sS

yste

mat

ic R

evie

w: N

o. o

f st

ud

ies,

1

Ko

sow

ski e

t al

. 200

9 PM

:194

8358

4 S

yste

mat

ic r

evie

w U

S/P

atie

nts

wh

o

rece

ived

ele

ctiv

e fa

cial

co

smet

ic

pro

ced

ure

s (e

.g.,

inje

ctab

le

fille

rs, i

mp

lan

ts,

bo

tulin

um

to

xin

tr

eatm

ent)

to

im

pro

ve f

acia

l

9 q

ues

tio

n-

nai

res

to

asse

ss f

acia

l ap

pea

ran

ce

N/A

In

ject

able

fille

rs

Imp

lan

ts

Bo

tulin

um

to

xin

No

t re

po

rted

V

alid

, rel

iab

le,

and

res

po

nsi

ve

inst

rum

ents

des

ign

ed

to m

easu

re p

atie

nt-

rep

ort

ed o

utc

om

es

follo

win

g s

urg

ical

an

d n

on

surg

ical

fa

cial

rej

uve

nat

ion

ar

e la

ckin

g. A

p

atie

nt-

rep

ort

ed

ou

tco

me

mea

sure

that

re

pre

sen

ts p

erce

ptio

ns

of f

acia

l co

smet

ic

surg

ery

pat

ien

ts a

nd

sa

tisfi

es a

ccep

ted

h

ealth

mea

sure

men

t cr

iteri

a is

Po

or

Ran

do

miz

ed C

on

tro

lled

Tri

al (

RC

T):

No

. of

stu

die

s, 1

Sc

lafa

ni e

t al

. 200

2 PM

:124

3743

2 R

CT

U

S/p

atie

nts

wit

h

age-

rel

ated

ch

ang

es in

th

e si

ze a

nd

co

nto

ur

of

the

lip

44 (

44)

3, 6

, 9, 1

2 m

o

Cym

etra

n

= 19

Z

ypla

st

n=

25

Inje

ctio

n t

o t

he

up

per

lip

b

etw

een

th

e o

rbic

ula

ris

ori

s m

usc

le a

nd

th

e o

verl

yin

g

mu

cocu

tan

eou

s ju

nct

ion

of

the

up

per

lip

Cym

etra

incr

ease

s th

e u

pp

er li

p b

ulk

, ve

rmili

on

, an

d lo

wer

lip

pro

ject

ion

Go

od


April 2011

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f st

ud

ies,

7

Bja

rnsh

olt

et

al.

2009

PM

:197

0913

3

Un

con

tro

lled

cl

inic

al t

rial

D

enm

ark/

pat

ien

ts

wit

h a

dve

rse

reac

tio

ns

afte

r in

ject

ion

of

po

lyac

ryla

mid

e g

el

8 14

d -

2yr

sin

ce

inje

ctio

n

n=7

Aq

uam

id

n=1

Inte

rfal

l n

=3 li

p

n=1

pen

is n

=1b

reas

t n

=1 t

ear

tro

ug

h

n=1

nas

ola

bia

l fo

ld

n=1

ch

eek

Res

ult

s p

rese

nte

d in

th

is r

epo

rt s

up

po

rt

the

idea

th

at r

ou

tin

e b

acte

rial

cu

ltu

re

swab

s d

etec

t o

nly

a

frac

tio

n o

f th

e b

acte

ria

in r

eact

ive

tiss

ues

inje

cted

wit

h

po

lyac

ryla

mid

e g

el.

Th

e fa

ct t

hat

on

e b

iop

sy d

id n

ot

sho

w

any

bac

teri

a d

id n

ot

excl

ud

e p

oss

ibili

ty o

f an

infe

ctio

n.

Po

or

de

Cas

sia

et a

l. 20

03

PM:1

4612

994

Clin

ical

tri

al

Sw

eden

/pat

ien

ts

un

der

go

ing

fa

cial

au

gm

enta

tio

n

59

2-16

mo

(9

mo

av

g)

Aq

uam

id

Inje

ctio

n

sub

cuta

neo

usl

y b

y re

tro

gra

de

linea

r tr

acin

g

inje

ctio

n

tech

niq

ue

for

lip

aug

men

tati

on

, ch

eekb

on

e en

larg

emen

t,

dee

p n

aso

lab

ial

fold

s, g

lab

ella

, ch

in

Aq

uam

id g

ives

a

pro

per

ly in

crea

sed

vo

lum

e w

ith

nat

ura

l el

asti

city

an

d v

isco

sity

Po

or

Oth

er F

iller

s U

nco

ntr

olle

d C

linic

al T

rial

: No

. of

stu

die

s, 7

H

an e

t al

. 200

6 PM

:165

0835

3 C

linic

al T

rial

K

ore

a/ p

atie

nts

u

nd

erg

oin

g

aug

men

tati

on

rh

ino

pla

sty

11 (

6)

12 m

o

Cu

ltu

red

hu

man

fi

bro

bla

sts

susp

end

ed

in R

esty

lan

e 0.

6-1.

0 m

l

Inje

ctio

n in

to t

he

sub

cuta

neo

us

laye

r o

f th

e n

asal

d

ors

um

Res

tyla

ne

wit

h

susp

end

ed c

ult

ure

d

hu

man

fib

rob

last

s h

as

the

po

ten

tial

to

be

use

d a

s a

lon

g-l

asti

ng

in

ject

able

so

ft-

tiss

ue

Po

or

Trea

cy e

t al

. 200

6 PM

:167

9264

5 C

linic

al T

rial

U

S/H

IV p

atie

nts

w

ith

fac

ial

lipo

dys

tro

ph

y

11 (

11)

3 an

d 1

8 m

o

Bio

Alc

amid

po

lyal

ylim

ide

gel

15.

0-30

.0 c

m3

Po

lyal

ylim

ide

gel

in

ject

ed in

to t

he

bu

ccal

, mal

ar,

and

tem

po

ral

area

s o

f th

e

face

, su

per

fici

al

to t

he

sup

erfi

cial

m

usc

ulo

a -p

on

euro

tic

Po

lyal

kylim

ide

gel

in

ject

ion

s ca

n le

ad

to s

ign

ifica

nt

clin

ical

an

d b

ehav

iora

l im

pro

vem

ents

in H

LS

pat

ien

ts

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

von

et

al. 2

005

PM:1

6163

108

Clin

ical

Tri

al

Den

mar

k,

Ger

man

y, It

aly,

N

eth

erla

nd

s,

Sp

ain

, Sw

eden

/P

atie

nts

u

nd

erg

oin

g

faci

al

aug

men

tati

on

an

d

enh

ance

men

t o

f fa

cial

co

nto

urs

d

ue

to a

gin

g,

acn

e, t

rau

ma,

or

surg

ery

251

(228

).

7, 2

8 d

3, 6

, 12

mo

A

qu

amid

0.2

-12.

0 m

l G

el a

dm

inis

tere

d

thro

ug

h t

he

sub

cuta

neo

us

tiss

ue

usi

ng

a

thin

nee

dle

. In

ject

ion

sta

rts

as t

he

nee

dle

is

wit

hd

raw

n f

rom

th

e n

aso

lab

ial

and

gla

bel

la

fold

s, d

epre

ssed

co

rner

s o

f th

e m

ou

th, p

erio

ral

wri

nkl

es, l

ip,

chin

, ch

eeks

, n

ose

, an

d

verm

illio

n b

ord

er

Aq

uam

id is

an

eas

y to

u

se s

oft

tis

sue

fille

r w

ith

lon

g-l

asti

ng

ti

ssu

e en

han

cem

ent

for

at le

ast

12 m

o

Po

or

von

et

al. 2

006

PM:1

6936

548

Un

con

tro

lled

cl

inic

al t

rial

G

erm

any/

pat

ien

ts

wit

h m

ean

ag

e o

f 48

yrs,

8%

m

ale

251

(101

) 24

mo

A

qu

amid

Nas

ola

bia

l an

d

gla

bel

la f

old

s,

dep

ress

ed

corn

ers

of

the

mo

uth

, an

d

per

iora

l wri

nkl

es

Faci

al c

on

tou

rin

g,

lip a

ug

men

tati

on

Th

e ef

fica

cy o

f p

oly

acry

lam

id

hyd

rog

el f

or

faci

al s

oft

-tis

sue

aug

men

tati

on

was

as

go

od

at

the

2yr

follo

win

g a

s th

at s

een

at

th

e 12

mo

vis

it.

Th

us,

th

e au

tho

rs

stat

e th

at a

lon

g-

last

ing

eff

ect

afte

r in

ject

ion

of

Aq

uam

id

can

be

Po

or


April 2011

Wo

lter

s et

al.

2009

PM

:192

0732

3 P

rosp

ecti

ve,

mu

ltic

ente

r tr

ial

Ger

man

y/G

ener

al

po

pu

lati

on

25

1 (8

1)

36 t

o 4

8 m

o

Cro

ss-l

inke

d

po

lyac

ryla

mid

e h

ydro

gel

Var

iou

s fa

cial

co

nto

uri

ng

lo

cati

on

s,

no

t ex

plic

itly

re

po

rted

Wh

erea

s b

iolo

gic

al

fille

rs a

re

com

ple

tely

or

par

tial

ly r

eab

sorb

ed

thro

ug

h e

nzy

mat

ic

deg

rad

atio

n, r

equ

irin

g

rep

eate

d in

ject

ion

s fo

r p

erm

anen

t fi

llin

g e

ffec

ts,

syn

thet

ic fi

llers

are

n

ot

deg

rad

ed a

nd

p

rod

uce

per

man

ent

resu

lts

afte

r o

ne

or

few

inje

ctio

ns,

b

ut

do

cto

rs h

ave

bee

n h

esit

ant

to u

se

no

nd

egra

dab

le fi

llers

, b

ecau

se a

nu

mb

er

of

adve

rse

reac

tio

ns

hav

e b

een

rep

ort

ed.

Th

e p

oly

acry

lam

ide

hyd

rog

el fi

ller

was

st

ill w

ell t

ole

rate

d

afte

r 36

to

48

mo

nth

s w

ith

no

lon

g-t

erm

u

nex

pec

ted

ad

vers

e ev

ents

an

d n

o lo

ss

of

fille

r

Po

or

Co

ho

rt S

tud

y: N

o. o

f st

ud

ies,

4

Ho

nig

200

8 PM

:186

5073

7 C

oh

ort

stu

dy

Ger

man

y/N

on

rela

ted

HIV

se

rop

osi

tive

p

atie

nts

wit

h

faci

al L

A

9 m

edia

n 2

yr

Bio

-Alc

amid

, 7

to 2

5 m

l in

ch

eek

1 to

3 m

l in

NLF

1

to 2

ml i

n li

p li

ne

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, ch

eek,

lip

lin

e T

he

pre

sen

t st

ud

y st

ron

gly

su

gg

ests

th

at B

io-A

lcam

id

is s

uit

able

fo

r th

e co

rrec

tio

n o

f re

mar

kab

le d

efec

ts

of

faci

al a

tro

ph

y,

oth

erw

ise

trea

tab

le

on

ly b

y su

rger

y w

ith

m

yofa

scia

l fre

e fl

aps.

Po

or

Kal

anta

r- H

orm

ozi

et a

l. 20

08

PM:1

9083

518

Ret

rosp

ecti

ve

Iran

/Pat

ien

ts w

ith

a

his

tory

of

PA

AG

in

ject

ion

s

600

2-5

yr

Po

lyac

ryla

mid

e g

el

PA

AG

) 54

2 in

var

iou

s fa

cial

lo

cati

on

s T

he

auth

ors

rec

om

men

d

that

co

mp

licat

ion

s fr

om

tre

atm

ent

wit

h

PA

AG

be

stu

die

d

furt

her

bef

ore

w

ides

pre

ad u

se o

f th

is s

oft

tis

sue

fille

r.

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Neg

red

o e

t al

. 200

6 PM

:171

9214

8 C

om

par

ativ

e,

pro

spec

tive

co

ho

rt s

tud

y

Sp

ain

/ HIV

-in

fect

ed p

atie

nts

p

rese

nti

ng

wit

h

anti

retr

ovi

ral-

as

soci

ated

fac

ial

lipo

atro

ph

y fo

r m

ore

th

an 6

mo

s

138

(n=8

re

ceiv

ed f

at,

n=2

5 re

ceiv

ed

po

ly-L

- la

ctic

aci

d,

and

n=1

05

rece

ived

p

oly

acry

la-

mid

e g

el)

96 w

k A

nal

og

ou

s fa

t o

bta

ined

b

y lip

osu

ctio

n, 5

0ml

Po

lyla

ctic

Aci

d, 3

-14m

l P

oly

acry

lam

ide

gel

, 4-

18m

l

Nas

ola

bia

l fo

lds

Th

e au

tho

rs’ c

on

clu

de

that

po

lyac

ryla

mid

e g

el p

rovi

des

th

e lo

ng

est

last

ing

res

ult

s o

f th

e th

ree

pro

du

cts

com

par

ed. H

ow

ever

, b

iod

egra

dab

le

pro

du

cts,

su

ch a

s fa

t an

d p

oly

lact

ic

acid

sh

ou

ld a

lso

b

e co

nsi

der

ed a

s vi

able

op

tio

ns

for

the

trea

tmen

t o

f fa

cial

lip

oat

rop

hy.

T

he

cho

ice

of

the

bes

t p

rod

uct

fo

r re

con

stru

ctiv

e p

urp

ose

s sh

ou

ld b

e m

ade

in c

on

cord

ance

w

ith

a p

hys

icia

n’s

cl

inic

al e

valu

atio

n

and

th

e p

atie

nt’

s p

refe

ren

ces.

Fair

Red

a-La

ri 2

008

PM:1

9083

517

Ret

rosp

ecti

ve

asse

ssm

ent

Ku

wai

t/P

atie

nts

tr

eate

d w

ith

P

AH

G f

or

soft

tis

sue

aug

men

tati

on

of

the

mal

ar a

rea

2136

3

mo

to

6 y

r P

oly

acry

lam

ide

hyd

rog

el,

1.5

to 5

ml

Per

iorb

ital

(te

ar

tro

ug

h, u

pp

er

lid),

tem

ple

, la

tera

l fac

e (g

on

ial a

ng

le

area

), b

ucc

al,

mal

ar, n

asal

, n

aso

lab

ial,

lip

and

ch

in, o

r an

y co

mb

inat

ion

of

the

abo

ve.

In t

he

exp

erie

nce

, PA

HG

is

saf

e fo

r fa

cial

so

ft

tiss

ue

aug

men

tati

on

, as

on

ly a

sm

all

nu

mb

er o

f si

de

effe

cts

occ

urr

ed d

uri

ng

th

e fo

llow

-up

per

iod

. P

AH

G p

rovi

ded

su

stai

nab

le a

nd

lo

ng

-las

tin

g r

esu

lts

and

hig

h p

atie

nt

sati

sfac

tio

n r

ate.

Lo

ng

er f

ollo

w u

p is

n

eces

sary

.

Po

or


April 2011

Cro

ss-s

ecti

on

al S

tud

y: N

o. o

f st

ud

ies,

1

Zap

pi e

t al

. PM

:180

8605

7 Fo

llow

-up

ev

alu

atio

n

stu

dy

US

/Pat

ien

ts tr

eate

d

wit

h L

IS f

or

dep

ress

ed s

cars

o

n t

he

face

35 s

amp

les

(25

pat

ien

ts)

1 to

23

yr

Liq

uid

inje

ctab

le s

ilico

ne

(LIS

), 0

.05-

0.2

ml

No

t re

po

rted

. A

s a

resu

lt o

f it

s h

igh

p

erm

anen

ce a

nd

in

ertn

ess,

wh

ich

is

refl

ecte

d b

y th

e la

ck

of

adve

rse

reac

tio

ns,

si

lico

ne

sho

uld

b

e re

gar

ded

as

a va

luab

le fi

ller,

at

leas

t fo

r th

e co

rrec

tio

n o

f sm

all d

epre

ssed

fac

ial

scar

s.

Po

or

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

16

Am

in e

t al

. 200

4 PM

:156

0682

6 R

etro

spec

tive

ca

se r

epo

rt

Fran

ce/6

4 yr

old

fe

mal

e U

S

citi

zen

1 5

mo

P

oly

acry

lam

ide

gel

D

erm

al in

ject

ion

s o

f p

oly

acry

lam

ide

gel

in c

hee

ks

Po

lyac

ryla

mid

e g

el

is p

ote

nti

ally

a

pro

mis

ing

syn

thet

ic

soft

tis

sue

fille

r, b

ut

exp

erie

nce

in t

he

US

is v

ery

limit

ed.

Th

e au

tho

rs r

epo

rt

the

firs

t ca

se o

f a

del

ayed

rea

ctio

n

to p

oly

acry

lam

ide

gel

inje

cted

into

th

e fa

ce f

or

soft

tis

sue

aug

men

tati

on

, in

th

eir

kno

wle

dg

e.

Po

or

Ap

te e

t al

. 200

3 PM

:129

7277

3 R

etro

spec

tive

ca

se r

epo

rt

US

/48

yr o

ld

wo

man

1

2 m

o

Cym

etra

(h

um

an c

adav

er

colla

gen

) Fo

reh

ead

T

he

mic

ron

izat

ion

o

f co

llag

en in

th

is

pro

du

ct is

su

ffici

ent

to a

llow

par

ticu

late

co

llag

en a

cces

s to

th

e co

roid

al v

ascu

latu

re.

Po

or

Ch

eng

et

al. 2

006

PM:1

6547

628

Ret

rosp

ecti

ve

case

ser

ies

Ch

ina/

Wo

men

ag

ed 2

4-45

yr

15

1-7

yr

Po

lyac

ryla

mid

e g

el

Face

, bre

asts

, leg

s It

is t

oo

ear

ly t

o a

sses

s th

e lo

ng

-ter

m e

ffica

cy

of

PA

AG

as

a cl

inic

ally

sa

fe, s

oft

tis

sue

filli

ng

m

ater

ial b

ecau

se o

f it

s u

nst

able

loca

lizat

ion

p

rop

oer

ty in

imp

lan

t re

gio

ns

and

its

ten

den

cy t

o m

ove

ea

sily

in r

esp

on

se t

o

gra

vity

an

d

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

des

crip

tio

nC

on

clu

sio

ns

Gra

de

Des

cam

ps

et a

l. 20

08

PM:1

8446

029

Cas

e re

po

rts

Fran

ce/p

atie

nts

w

ith

ch

ron

ic

hep

atit

is C

tr

eate

d w

ith

al

ph

a- in

terf

ero

n 2

Cas

e 1

- 5

yr p

ost

tr

eatm

ent

Cas

e 2

- 2

year

s p

ost

- tr

eatm

ent

Cas

e 1

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nkn

ow

n

per

man

ent

der

mafi

ller

Cas

e 2

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yalu

ron

ic

acid

Cas

e 1

- m

eslo

lab

ial

and

nas

ola

bia

l fo

lds

Cas

e 2

- p

erib

ucc

al

and

lio

n’s

w

rin

kles

Th

e au

tho

rs s

tate

th

at p

atie

nts

wit

h

sarc

oid

osi

s an

d

pat

ien

ts in

fect

ed w

ith

H

CV

sh

ou

ld b

e aw

are

of

the

risk

of

fore

ign

b

od

y g

ran

ulo

mas

an

d

be

excl

ud

ed f

rom

an

y fi

ller

inje

ctio

ns.

Th

e au

tho

rs a

lso

fee

l th

at

a b

loo

d t

est

for

HC

V

sho

uld

be

un

der

take

n

bef

ore

inje

ctio

n a

d

erm

a fi

ller.

Po

or

Go

ldm

an 2

009

PM:1

9207

334

Cas

e R

epo

rt

US

A, I

taly

/46

yr

old

wo

man

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(1)

2 d

fo

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fi

nal

tre

atm

ent

thro

ug

h 1

0mo

fo

llow

ing

fin

al

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tmen

t

Aq

uam

id

(Po

lyac

ryla

mid

e g

el)

3.0m

l in

200

2 0.

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n

Au

gu

st 2

004

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n A

ug

ust

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ruar

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er 2

007

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n N

ove

mb

er 2

007

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uri

ng

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ug

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old

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p in

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ug

ust

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-up

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ebru

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2007

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ove

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Au

tho

rs b

elie

ve t

hat

p

atie

nt

pre

sen

ts t

he

firs

t ca

se r

epo

rt o

f p

ress

ure

-in

du

ced

m

igra

tio

n o

f a

per

man

ent

soft

-tis

sue

fille

r, a

nd

th

e au

tho

rs

susp

ect

that

th

e p

ress

ure

gen

erat

ed

by

inje

ctio

n o

f b

iod

egra

dab

le fi

llers

to

au

gm

ent

lip s

ize

forc

ed a

dis

sect

ion

al

on

g t

issu

e p

lan

es

of

the

per

man

ent

enca

psu

late

d fi

ller.

Po

or


April 2011

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

16

Gri

mal

di e

t al

. 200

8 PM

:186

5073

8 C

ase

Rep

ort

It

aly/

50 y

r o

ld

fem

ale

wit

h

Ro

mb

erg

sy

nd

rom

e o

f th

e le

ft f

ace,

wh

ich

sh

e h

as h

ad f

or

20yr

s

1 N

ot

rep

ort

ed

Po

lyg

lact

ic a

cid

an

d f

at

fro

m t

he

abd

om

inal

ar

ea

Of

fat:

-

15 m

l in

th

e ri

gh

t zy

go

mat

ic r

egio

n

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ml i

n le

ft c

hee

k -1

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l in

bu

ccal

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me

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l in

th

e le

ft

up

per

eye

lid

-15

ml i

n t

he

left

te

mp

ora

l are

a

Res

ult

s o

bta

ined

in

this

rep

ort

pro

ve t

he

effi

cacy

of

com

bin

ing

sk

in t

hic

ken

ing

u

sin

g p

oly

gla

ctic

ac

id w

ith

th

e C

ole

man

tec

hn

iqu

e fo

r re

con

stru

ctin

g

thre

e- d

imen

sio

nal

p

roje

ct o

f fa

ce

con

tou

r to

res

tore

th

e su

per

fici

al d

ensi

ty

of

faci

al t

issu

es. T

he

auth

ors

sta

te t

hat

th

e sa

tisf

acti

on

of

the

pat

ien

t co

nfi

rms

the

qu

alit

y o

f th

e re

sult

s.

Po

or

Jham

et

al.

PM:1

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600

Cas

e re

po

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and

co

mp

reh

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ve

liter

atu

re

revi

ew

Var

iou

s/G

ener

al

po

pu

lati

on

56

V

ario

us

Up

per

/low

er li

p,

NLF

, ch

eek

Po

o

Kan

chw

ala

et a

l. 20

05PM

:159

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8.

Ret

rosp

ecti

ve

Cas

e S

erie

sU

S/p

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u

nd

erg

oin

g

faci

al

aug

men

tati

on

976

3, 6

, 9, 1

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uto

log

ou

s fa

t n

=697

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afo

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=52

Res

tyla

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n=8

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adie

sse

n=1

41

Nas

ola

bia

l fo

lds,

lip

s, g

lab

ella

Su

cces

sfu

l fat

tr

ansp

lan

tati

on

ap

pea

rs t

o b

e th

e p

refe

rred

met

ho

d

for

the

trea

tmen

t o

f vo

lum

e lo

ss t

o t

he

face

.

Poo

r

Kar

agoz

og

lu e

t al

. 20

08

PM:1

8313

268

Cas

e re

po

rt

Net

her

lan

ds/

39

yr o

ld w

om

an

refe

rred

by

her

den

tist

b

ecau

se o

f a

smal

l mo

bile

su

bm

uco

sal

swel

ling

in t

he

left

ch

eek

1 p

rese

nte

d 3

yr

sin

ce

trea

tmen

t;

follo

w u

p o

f 6m

os

po

st

pre

sen

tati

on

Aq

uam

id

(po

lyac

ryla

min

de

gel

) N

aso

lab

ial f

old

In

this

cas

e bo

th s

urge

on

and

path

olog

ist w

ere

mis

led

by th

e in

itial

ly

nega

tive

hist

ory

of

the

patie

nt a

nd b

y th

e hi

stop

atho

logi

c as

pect

s of

the

biop

sy s

peci

men

, ev

en m

imic

king

m

ucoe

pide

rmoi

d

carc

inom

a.

App

aren

tly, c

osm

etic

in

terv

entio

ns h

ave

beco

me

so c

omm

on in

ou

r so

ciet

y th

at n

eith

er

doct

ors

nor

patie

nts

may

ask

abo

ut o

r m

entio

n th

em. S

ome

patie

nts

may

be

relu

ctan

t to

disc

lose

su

ch p

roce

dure

s to

th

eir

doct

or.

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

Fo

llo

w-u

pT

reat

men

tIn

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ion

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on

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ns

Gra

de

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. 20

06

PM:1

6545

711

Ret

rosp

ecti

ve

case

rep

ort

B

razi

l/61

yr o

ld

wh

ite

wo

man

1

8-14

mo

S

ing

le d

ose

Aq

uam

id

(2.5

% p

oly

acry

lam

ide)

S

ing

le d

ose

of

Aq

uam

id in

ject

ed

in t

he

nas

ola

bia

l fo

ld.

Firs

t ca

se in

au

tho

r’s

kno

wle

dg

e o

f an

in

trao

ral f

ore

ign

bo

dy

reac

tio

n r

esu

ltin

g

fro

m A

qu

amid

ap

plic

atio

n in

th

e n

aso

lab

ial f

old

.

Po

or

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

16

Lah

iri e

t al

. 200

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ed

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9

121.

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(s

ynth

etic

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lym

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p

oly

akyl

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ncl

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d

wit

h c

olla

gen

)

Inje

ctio

ns

for

faci

al

and

ch

est

wal

l d

efo

rmit

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Alc

amid

is v

ery

eng

ou

rag

ing

fo

r fa

cial

lo

po

atro

ph

y, c

hes

t w

all d

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rmit

ies,

as

an a

dju

nct

to

bre

ast

reco

nst

ruct

ion

, an

d

corr

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on

of

oth

er

typ

es o

f co

ng

enit

al

and

acq

uir

ed c

on

tou

r d

efo

rmit

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e co

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licat

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e ve

ry lo

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Cas

e

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ach

bu

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rst

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400

ml i

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Cas

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Pra

ctit

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ho

p

erfo

rmed

all

ori

gin

al

trea

tmen

ts w

as f

ou

nd

to

no

t h

ave

a m

edic

al

licen

se a

nd

was

su

bse

qu

entl

y ar

rest

ed

afte

r in

vest

igat

ion

.

Po

or


April 2011

Para

da

et a

l. 20

05

PM:1

6276

149

His

tolo

gic

p

rep

arat

ion

s fr

om

11

bio

psi

es

colle

cted

ove

r a

two

yea

r p

erio

d.

Bra

zil

11

No

t re

po

rted

R

esty

lan

e (h

yalu

ron

ic

acid

), M

etac

ril

(po

lym

eth

yl -

met

hac

ryla

te),

A

qu

amid

(p

oly

acry

lam

ide)

, N

ew-F

ill (

po

lyla

ctic

ac

id),

A

rtec

oll

(po

lym

eth

yl -

met

hac

ryla

te

susp

end

ed in

a

colla

gen

so

luti

on

).

Bio

psi

es fi

xed

in

10%

fo

rmal

in.

Th

e au

tho

rs p

ost

ula

te

that

incr

easi

ng

n

um

ber

s o

f “b

izar

re

fore

ign

bo

dy-

typ

e g

ran

ulo

mat

ou

s re

acti

on

s in

th

e o

ral

faci

al r

egio

ns

of

mid

dle

-ag

ed w

om

en”

are

du

e to

inje

ctio

ns

wit

h o

ne

or

mo

re o

f th

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fille

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or

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:191

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gm

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451

wk,

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3-6m

os

po

sttr

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ent;

at

tim

e o

f re

po

rt, m

edia

n

follo

w-u

p t

ime

for

pat

ien

ts

was

13

mo

s

Per

mac

ol (

xen

og

raft

)n

asal

reg

ion

Au

tho

rs p

rese

nt

the

firs

t re

po

rted

ser

ies

o

f P

erm

aco

l use

in

au

gm

enta

tio

n

rhin

op

last

y. A

uth

ors

st

ate

that

bec

ause

lo

ng

er t

erm

fo

low

-u

p o

f p

atie

nts

is

req

uir

ed b

efo

re

defi

nit

e co

ncl

usi

on

s ca

n b

e d

raw

n o

n it

s lo

ng

-ter

m s

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ess,

th

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on

clu

de

that

th

e u

se o

f P

erm

aco

l as

an

alt

ern

ativ

e to

au

tog

eno

us

cart

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e g

raft

in a

ug

men

tati

on

rh

ino

pla

sty

des

erve

s fu

rth

er e

valu

atio

n.

Poo

r

Cas

e S

erie

s/R

epo

rt: N

o. o

f st

ud

ies,

16

Ro

ssn

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t al

. 200

9 PM

:192

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spec

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ca

se s

erie

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sin

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n a

dve

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reac

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ns

to

inje

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llers

Ger

man

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tr

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a

met

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ller

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th

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34

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dro

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late

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Fille

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ject

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95

are

as a

mo

ng

th

e 34

pat

ien

ts.

Co

mm

on

are

as:

NLF

s (4

6.3%

) C

orn

ers

of

the

mo

uth

(17

.9%

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lab

ella

(17

.9%

) U

pp

er li

p (

12.6

%)

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mal

ive

is a

lon

g-

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ller

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h a

bio

deg

rad

able

p

art

(HA

) an

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n

on

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deg

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p

art

(met

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ryla

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A

lth

ou

gh

th

ese

ing

red

ien

ts a

re

wid

ely

acce

pte

d

as c

om

pat

ible

su

bst

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s, t

he

stu

dy

was

ab

le t

o s

ho

w

a la

rge

nu

mb

er o

f p

atie

nts

dev

elo

pin

g

adve

rse

Po

or


Volume 64, Number 4

Ap

pen

dix

A. C

on

t’d

Stu

dy

Des

ign

Co

un

try/p

op

ula

tio

n

typ

eSa

mp

le s

ize

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llo

w-u

pT

reat

men

tIn

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mafi

llers

w

ho

d e

velo

ped

a

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tio

n in

on

e o

r m

ore

of

the

trea

ted

are

as

56 (

n=5

5 fe

mal

es, n

=1

mal

es);

8

pat

ien

ts w

ere

excl

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o

that

n=4

8 re

mai

ned

fo

r fu

rth

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anal

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No

t re

po

rted

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deg

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llow

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), c

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=

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=16)

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tho

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pp

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th

e n

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fo

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s to

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fille

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d t

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du

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hav

e to

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care

fully

mo

nit

ore

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sin

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he

adve

rse

even

ts a

sso

ciat

ed

wit

h t

hes

e p

rod

uct

s ar

e es

pec

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lt

to t

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.

Poo

r

J Am AcAd dermAtol

April 2011S85.e69 Hanke et al

Ap

pen

dix

B.

ASP

S/A

AD

evi

den

ce t

able

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d c

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listi

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die

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ller t

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Stu

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oll

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Ad

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ID:1

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Ass

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n to

o

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rve

tran

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Ult

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ject

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e N

LF o

n o

ne

sid

e o

f th

e fa

ce. I

n a

ll su

bje

cts,

the

NLF

on

th

e o

ther

sid

e o

f th

e fa

ce w

as t

reat

ed w

ith

Z

ypla

st. T

he

vast

maj

ori

ty

of s

ub

ject

s h

ad o

nly

on

e tr

eatm

ent

visi

t.

1. F

ive-

po

int W

AS

2. E

ffica

cy

3. P

atie

nt

sati

sfac

tio

n

Freq

uen

cy a

nd

sev

erit

y o

f tre

atm

ent-

site

re

acti

on

s w

ere

sim

ilar f

or a

ll fil

lers

. Th

ere

wer

e n

o t

reat

men

t-re

late

d A

Es e

ven

ts

oth

er t

han

th

ose

loca

lized

to t

he

area

of

inje

ctio

n.

In a

ll tr

eatm

ent

gro

up

s, th

e m

ajo

rity

of

reac

tio

ns

at t

he

trea

tmen

t si

te w

ere

mild

to m

od

erat

e in

sev

erit

y, d

id n

ot

req

uir

e in

terv

enti

on

, an

d la

sted

7 d

ays

or l

ess.

Ther

e w

as o

ne

sig

nifi

can

t A

E re

po

rted

: ste

rile

ab

sces

s at

th

e in

ject

ion

si

te o

ccu

rrin

g 4

mo

aft

er t

reat

men

t w

ith

bov

ine

colla

gen

. AE

pat

tern

s an

d

inci

den

ce w

ere

sim

ilar b

etw

een

Cau

casi

an

and

no

n-C

auca

sian

su

bje

cts.

Bee

r, 20

07 P

MID

: 17

6619

35

USA

/Wo

men

15

(15)

2

wk,

3, 4

.5,

6 m

o

Res

tyla

ne

(HA

gel

), 0.

7– 2

.1 m

l H

ylaf

orm

, 1.6

ml

Hyl

afo

rm, 1

.6 m

l (a

vera

ge)

(n =

150

)

A p

hys

icia

n o

r nu

rse

adm

inis

tere

d a

ran

do

mly

as

sig

ned

tre

atm

ent

to

on

e si

de

of e

ach

pat

ien

t’s

NLF

an

d t

he

oth

er

trea

tmen

t to

th

e N

LF o

n

the

op

po

site

sid

e.

1. W

SRS

sco

re

2. G

AIS

sco

reA

Es a

sso

ciat

ed w

ith

bo

th H

A g

el a

nd

Hyl

an B

Pl

us

inje

ctio

ns

incl

ud

ed b

ruis

ing,

red

nes

s, sw

ellin

g, p

ain

, itc

hin

g, a

nd

no

du

les.

All

wer

e o

f mild

to m

od

erat

e se

veri

ty a

nd

la

sted

sev

eral

day

s.


Volume 64, Number 4A

pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e m

easu

res

Ad

vers

e ev

ents

Car

ruth

ers

et

al.,

2005

PM

ID:1

6416

643

Can

ada/

Pati

ents

see

kin

g

cosm

etic

co

rrec

tio

n

of m

od

erat

e to

sev

ere

nas

ola

bia

l fo

lds

150(

140)

3,

4.5

, 6 m

o R

esty

lan

e Pe

rlan

e, 1

.3

ml (

aver

age)

(n

= 1

50)

Hyl

afo

rm, 1

.6 m

l H

ylaf

orm

, 1.6

ml

(ave

rag

e)

(n =

150

)

Co

ntr

alat

eral

inje

ctio

n o

f ea

ch fi

ller i

nto

th

e m

id o

r d

eep

der

mis

nas

ola

bia

l fo

lds

1. W

SRS

sco

re

2. G

AIS

sco

reSw

ellin

g, p

ain

, an

d re

dn

ess

wer

e th

e m

ost

co

mm

on

an

d o

ccu

rred

mo

re fr

equ

entl

y in

R

esty

lan

e Pe

rlan

e th

an in

Hyl

afo

rm (4

1.3%

vs

. 21.

3%).

Car

ruth

ers

etal

., 20

03 P

MID

: 12

8593

78

Can

ada/

Ad

ult

fem

ale

sub

ject

s w

ith

m

od

erat

e to

sev

ere

gla

bel

lar r

hyt

ides

38

32 w

k N

ASH

A (R

esty

lan

e)

(n =

19)

B

otu

linu

m to

xin

typ

e A

+ N

ASH

A

(1 w

k la

ter)

(n

= 1

9)

1 cm

ab

ove

the

sup

rao

rbit

al

no

tch

(on

bo

th s

ides

)2.

Glo

bal

imp

rove

men

t at

16

wk

1. M

edia

n t

ime

for r

etu

rn to

p

rein

ject

ion

fu

rro

w

Mild

ad

vers

e ev

ents

rep

ort

ed b

y a

maj

ori

ty o

f th

e su

bje

cts,

rela

ted

to m

ild to

mo

der

ate

ten

der

nes

s an

d s

wel

ling

in b

oth

gro

up

s. N

o s

ign

ifica

nt

diff

eren

ce b

etw

een

th

e tw

o

gro

up

s.

Des

sy e

t al

., 20

08

PMID

:188

3304

3 It

aly/

Pati

ents

wit

h c

lear

si

gn

s o

f pre

mat

ure

fa

cial

ag

ing

100

1, 3

, 6, 1

2 m

oW

ipel

ine

(H

A c

on

cen

trat

ion

, 1.

6%)

Wip

elin

e

(HA

co

nce

ntr

atio

n,

2.0%

)

Site

: fo

ld a

nd

wri

nkl

es in

th

e fa

ce

Thre

e se

ssio

ns

wit

h 4

-wk

inte

rval

s b

etw

een

th

em

VAS

sco

re to

ev

alu

ate

turg

idit

y,

elas

tici

ty, a

nd

lu

min

osi

ty.

Pro

du

cts

wer

e w

ell t

ole

rate

d a

nd

no

ad

vers

e re

acti

on

s w

ere

ob

serv

ed.

Glo

gau

et

al.,

2008

PM

ID:

1854

7173

USA

/Gen

eral

po

pu

lati

on

283

12

wk

Res

tyla

ne

(NA

SHA

, sm

all)

(n =

142

)Pe

rlan

e (N

ASH

A, l

arg

e)

(n =

141

)

Mid

face

vo

lum

e co

rrec

tio

n

of t

he

NLF

s an

d o

ral

com

mis

sure

s

(mar

ion

ette

lin

es)

AEs

on

ly

Tota

l of 3

36 lo

cal-

rela

ted

AEs

12

wk

of

follo

w-u

p t

reat

men

t. M

ost

co

mm

on

wer

e b

ruis

ing,

ten

der

nes

s, ed

ema,

an

d p

ain

.

1021

tota

l in

ject

ion

sit

esTo

uch

-up

inje

ctio

ns

afte

r. In

pat

ien

ts in

ject

ed

wit

h P

erla

ne,

wer

e d

isco

ura

ged

to p

aral

lel

clin

ical

pra

ctic

e, w

her

e co

rrec

tio

n is

usu

ally

co

mp

lete

d in

a s

ing

le

sess

ion

.

Inci

den

ce o

f lo

cal A

Es w

as h

igh

er a

t 72

hr

afte

r in

ject

ion

co

mp

ared

wit

h 2

wk

afte

r. In

pat

ien

ts in

ject

ed w

ith

Per

lan

e, a

ll A

Es

wer

e re

solv

ed b

y w

eek

2.

J Am AcAd dermAtol


Go

ldm

an e

t al

., 20

07 P

MID

: 17

4515

75

USA

/Pat

ien

ts w

ith

p

rom

inen

t n

aso

lab

ial

fold

s

36 (3

3)

56 d

ays

Res

tyla

ne,

alo

ne

and

in

co

mb

inat

ion

w

ith

lase

r/RF

/IPL

Nas

ola

bia

l fo

lds

(tre

ated

w

ith

HA

gel

imp

lan

tati

on

o

n o

ne

sid

e o

f th

e fa

ce

and

HA

gel

follo

wed

by

on

e o

f th

e n

on

abla

tive

la

ser/

RF/I

PL t

her

apie

s o

n

the

con

tral

ater

al s

ide

of

the

face

)

Clin

ical

effi

cacy

u

sin

g S

ever

ity

Rat

ing

Sca

le

(1–5

) bet

wee

n

HA

alo

ne

and

th

ose

tr

eate

d w

ith

co

nco

mit

ant

HA

/las

er/R

F/IP

LPa

tien

t se

lf-as

sess

men

t u

sin

g G

AIS

(0

–4) b

etw

een

H

A a

lon

e an

d t

ho

se

trea

ted

wit

h

con

com

itan

t H

A/l

aser

/RF/

IPL

Ther

e w

ere

six

AEs

rep

ort

ed d

uri

ng

this

stu

dy.

Tw

o o

f th

ese,

a s

erio

us

AE

of m

yoca

rdia

l in

farc

tio

n (o

f mo

der

ate

inte

nsi

ty) a

nd

a

no

nse

rio

us

even

t o

f an

emia

(of m

ild

inte

nsi

ty),

wer

e co

nsi

der

ed u

nre

late

d

to t

he

stu

dy.

Th

ree

adve

rse

exp

erie

nce

s (h

erp

es s

imp

lex

viru

s re

acti

vati

on

on

th

e u

pp

er li

p, m

ild e

ryth

ema

afte

r IPL

, an

d

bru

isin

g) w

ere

pro

bab

ly re

late

d to

th

e st

ud

y an

d w

ere

of m

ild in

ten

sity

. An

oth

er

adve

rse

exp

erie

nce

(pal

pab

le c

hee

k lu

mp

) p

oss

ibly

rela

ted

to s

tud

y tr

eatm

ent

was

al

so o

f mild

inte

nsi

ty. T

he

sub

ject

wit

h

bru

isin

g d

id n

ot

rece

ive

trea

tmen

t o

n d

ay

14 b

ut

com

ple

ted

th

e re

st o

f th

e st

ud

y.

Gri

mes

et

al.,

2009

PM

ID:

1973

5512

USA

/Pat

ien

ts w

ith

Fi

tzp

atri

ck s

kin

typ

es

IV, V

, or V

I

Stu

dy

1: 1

60

24 w

k St

ud

y 1:

Ju

véd

erm

U

ltra

, Ult

ra P

lus,

and

30

and

Zyp

last

co

llag

en

Nas

ola

bia

l fo

lds

1. N

aso

lab

ial f

old

se

veri

ty

Stu

dy

1: T

her

e w

ere

no

occ

urr

ence

s o

f hyp

erse

nsi

tivi

ty o

r hyp

ertr

op

hic

sc

arri

ng,

an

d n

o in

crea

sed

inci

den

ce o

f h

yper

pig

men

tati

on

or h

ypo

pig

men

tati

on

in

no

n-C

auca

sian

vs.

Cau

casi

an s

ub

ject

s. St

ud

y 2:

119

Stu

dy

2: H

ylaf

orm

,Hyl

afo

rm

Plu

s, an

d C

apti

qu

e St

ud

y 2:

Th

ere

was

no

occ

urr

ence

of

kelo

id fo

rmat

ion

, hyp

ertr

op

ic s

carr

ing,

h

ypo

pig

men

tati

on

, or h

yper

sen

siti

vity

, an

d t

hre

e in

stan

ces

of m

ild

hyp

erp

igm

enta

tio

n.

Ham

ilto

n e

t al

., 20

07 P

MID

: 18

0860

56

USA

/Pat

ien

ts

un

der

go

ing

der

mal

au

gm

enta

tio

n o

f N

LFs

433

0, 6

, 24

wk

Res

tyla

ne

Bo

th N

LFs

1. ID

-ST,

IgE

anti

-NA

SHA

im

mu

no

assa

y

42 s

yste

mic

ad

vers

e ex

per

ien

ces

wer

e re

po

rted

by

37 p

arti

cip

ants

. All

bu

t o

ne

wer

e ju

dg

ed b

y in

vest

igat

ors

to b

e u

nre

late

d to

NA

SHA

ad

min

istr

atio

n.

Perl

ane

2. S

ero

log

ic

resu

lts

3. 2

4-w

k ID

-ST

bio

psi

es

Ko

no

et

al.,

2008

PM

ID:

1854

7178

Jap

an

10 (1

0)

3, 6

, 9, 1

2 m

o

Res

tyla

ne,

SC

HA

(n

= 1

0)

Pura

gen

, DC

HA

(n

=10

)

On

e si

de

of e

ach

pat

ien

t’s

gla

bel

lar l

ines

was

tre

ated

w

ith

SC

HA

an

d t

he

oth

er

sid

e w

as t

reat

ed w

ith

D

CH

A.

1. C

linic

al e

ffica

cy

2. C

om

par

sio

nN

ot

rep

ort

ed

Levy

et

al.,

2009

PM

ID:

1920

7322

Fran

ce/S

ub

ject

s w

ith

m

od

erat

e to

sev

ere

bila

tera

l NLF

s

60

No

ne

Juvé

der

m U

ltra

3,

wit

h/

wit

ho

ut

pre

inco

rpo

rate

d

lido

cain

e; 0

.62

ml

For e

ach

su

bje

ct, t

he

NLF

on

o

ne

sid

e w

as ra

nd

om

ly

assi

gn

ed to

tre

atm

ent

wit

h H

A +

lid

oca

ine,

an

d

the

op

po

site

to t

reat

men

t w

ith

HA

gel

alo

ne.

1. P

hys

icia

n

asse

ssm

ent

pai

n

2. S

ub

ject

as

sess

men

t o

f p

ain

3. E

ase

of i

nje

ctio

n

Seve

rity

an

d fr

equ

ency

of i

nje

ctio

n-s

ite

reac

tio

ns

wer

e si

mila

r fo

r bo

th t

reat

men

ts

and

loca

lized

. Mo

st w

ere

mild

to m

od

erat

e in

sev

erit

y, d

id n

ot

req

uir

e in

terv

enti

on

, an

d la

sted

<5

day

s.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e m

easu

res

Ad

vers

e ev

ents

Lin

dq

vist

et

al.,

2005

PM

ID:

1562

2265

No

rway

an

d S

wed

en/

Pati

ents

wit

h

pro

min

ent

NLF

s

68 (4

3)

2, 4

, 6, 9

, 12

mo

Pe

rlan

e (n

= 6

8)

(on

e n

aso

lab

ial

fold

)

Intr

ader

mal

inje

ctio

n to

th

e N

LFs

1. W

SRS

asse

ssm

ent

On

ly m

ino

r ad

vers

e ev

ents

at

6 m

o a

nd

no

ne

at 1

2 m

o.

Zyp

last

(n =

68)

(c

on

tral

ater

al

nas

ola

bia

l fo

ld)

2. G

AIS

sco

re

Lup

o e

t al

., 20

08 P

MID

: 18

1762

33

USA

/Su

bje

cts

p

rese

nti

ng

wit

h

seve

re N

LF ra

ted

as

3 o

r ab

ove

87 (8

2)

4, 8

, 12,

16,

20

, 24,

48

wk

Juvé

der

m U

ltra

Plu

s (H

A),

1.7

ml f

or

init

ial t

reat

men

t, 0.

6 m

l fo

r rep

eate

d

trea

tmen

t

Sub

ject

s ra

nd

om

ized

to

trea

tmen

t w

ith

Ju

véd

erm

U

ltra

Plu

s in

on

e N

LF a

nd

Z

ypla

st in

th

e o

pp

osi

te

NLF

1. E

ffica

cy, i

nit

ial

trea

tmen

t p

erio

d

Occ

urr

ence

of t

reat

men

t-si

te re

acti

on

s w

as

sim

ilar f

or u

véd

erm

Ult

ra P

lus

and

Zyp

last

.

Zyp

last

(bov

ine

colla

gen

) 70

(81%

) of s

ub

ject

s re

turn

ed fo

r co

mp

limen

tary

rep

eate

d

trea

tmen

t w

ith

Ju

véd

erm

U

ltra

Plu

s, p

erfo

rmed

b

etw

een

24

and

36

wk

2. P

atie

nt

sati

sfac

tio

n,

init

ial

trea

tmen

t p

erio

d

Maj

ori

ty o

f in

div

idu

al re

acti

on

s la

sted

no

m

ore

th

an 7

day

s, w

ere

mild

or m

od

erat

e in

sev

erit

y, a

nd

req

uir

ed n

o fu

rth

er

inte

rven

tio

n.

3. E

ffica

cy,

rep

eate

d

trea

tmen

t p

erio

d

Exam

ple

s: Er

yth

ema,

ind

ura

tio

n, p

ain

, ed

ema,

no

du

le, b

ruis

ing,

pru

ritu

s, an

d

dis

colo

rati

on

.

Man

et

al.,

2008

PM

ID:

1843

0173

Can

ada/

Fem

ale

p

atie

nts

wh

o

dem

on

stra

ted

d

erm

al t

hin

nin

g o

f th

e d

ors

al h

and

s

10 (1

0)

1 w

k, 1

, 3, 6

m

o

Res

tyla

ne

(HA

), 1.

4 m

l (n

= 1

0)

Co

smo

Plas

t (C

olla

gen

), 2.

0 m

l (n

= 1

0)

Pati

ents

wer

e ra

nd

om

ized

to

rece

ived

tw

o v

ials

to

eit

her

th

eir r

igh

t o

r lef

t h

and

. Tw

o v

ials

o

f co

llag

en w

ere

adm

inis

tere

d in

to t

he

con

tral

ater

al h

and

.

1. T

ole

rab

ility

(0

–3)

2. P

atie

nt

sati

sfac

tio

n

(1–5

) 3.

Cle

aran

ce S

core

(1

-5),

asse

ssed

b

y fo

ur b

lind

ed

ind

epen

den

t o

ard

-cer

tifie

d

inve

stig

ato

rs

Ad

vers

e si

de

effe

cts

rep

ort

ed w

ith

inje

ctio

ns

incl

ud

ed p

ain

, tin

glin

g, a

nd

bru

isin

g.

On

e p

atie

nt

exp

erie

nce

d a

no

du

le fo

rmat

ion

at

th

e co

llag

en in

ject

ion

sit

e th

at re

solv

ed

by

6 m

o.

J Am AcAd dermAtol


Mo

ers-

Car

pi e

t al

., 20

07 P

MID

: 18

0860

52

Euro

pe/

Enro

lled

p

atie

nts

had

m

od

erat

e o

r sev

ere

NLF

s

205

192)

4,

8, 1

2 m

o

Rad

iess

e (C

aHA

), 2.

21

ml t

ota

l vo

lum

e

(n =

70)

Pati

ents

tre

ated

wit

h e

ith

er

CaH

A g

el o

r HA

for t

he

corr

ecti

on

of b

oth

NLF

s. N

earl

y al

l pat

ien

ts (n

=

189)

rece

ived

a to

uch

-up

tr

eatm

ent

at 4

mo.

1. P

atie

nt

sati

sfac

tio

n

No

ser

iou

s ad

vers

e ev

ents

req

uir

ing

in

terv

enti

on

wer

e re

po

rted

at

any

tim

e p

oin

ts fo

r an

y o

f th

e in

ject

ed m

ater

ials

.

Juvé

der

m 2

4

(HA

-1A

), 4.

78 m

l to

tal v

olu

me

(n

= 3

3)

2. In

vest

igat

or

GA

IS a

nal

ysis

Juvé

der

m 2

4HV

(H

A-1

B),

2.94

ml

tota

l vo

lum

e

(n =

33)

3. W

RSR

anal

ysis

Perl

ane

(HA

-2),

2.89

ml

tota

l vo

lum

e

(n =

65)

Mo

ers-

Car

pi

et a

l., 2

008

PMID

:180

9319

9

Ger

man

y an

d S

pai

n/

Mo

der

ate

to s

ever

e N

LFs

(3 o

r on

WSR

S)

60 (5

8)

6, 9

, 12

mo

R

adie

sse

Res

tyla

ne

Volu

me

equ

ired

for

corr

ecti

on

in C

aHA

-tr

eate

d fo

ld w

as

30%

less

th

an t

he

volu

me

of N

ASH

A.

Pati

ents

rece

ived

tw

o

inje

ctio

ns

3 m

o a

par

t. A

t th

e in

itia

l vis

it, p

atie

nt

was

tre

ated

wit

h C

aHA

to

co

rrec

t o

ne

NLF

an

d

NA

SHA

to c

orr

ect

the

oth

er N

LF. A

t th

e 3-

mo

vi

sit,

pat

ien

ts re

ceiv

ed a

to

uch

-up

tre

atm

ent

in

bo

th fo

lds.

1. G

AIS

rati

ng

s

2. B

lind

ed

eval

uat

ors

ra

tin

g

Bo

th p

rod

uct

s w

ere

safe

an

d w

ell t

ole

rate

d.

No

ser

iou

s ev

ents

wer

e re

po

rted

wit

h

eith

er t

reat

men

t.

Fou

r AEs

wer

e re

po

rted

: tw

o h

emat

om

as,

on

e n

od

ule

, an

d o

ne

extr

usi

on

(of 1

18

fold

s in

ject

ed t

wo

tim

es e

ach

du

rin

g t

he

cou

rse

of t

he

stu

dy)

. Th

e tw

o h

emat

om

as

reso

lved

in 4

–5 d

ays

wit

h n

o fu

rth

er

com

plic

atio

ns.

The

no

du

le w

as t

reat

ed

wit

h 0

.2 m

l of t

riam

cin

olo

ne

acet

on

ide

and

was

cle

ared

in 1

4 d

ays.

The

extr

usi

on

ap

pea

red

in a

n N

ASH

A-t

reat

ed fo

ld. I

t w

as t

reat

ed w

ith

an

tib

ioti

cs a

nd

reso

lved

w

ith

ou

t co

mp

licat

ion

s. N

arin

s et

al.

2003

PM

ID:

1278

6700

USA

/Co

rrec

tio

n o

f n

aso

lab

ial f

old

s 13

8 (1

38)

2, 4

, 6 m

o

Res

tyla

ne

(n =

138

) Z

ypla

st (n

= 1

38)

Inje

ctio

n o

f eac

h m

ater

ial t

o

con

tral

ater

al n

aso

lab

ial

fold

s

1. W

SRS

2. G

AIS

Trea

tmen

t-re

late

d A

Es w

ere

rep

ort

ed

in 3

8.4%

of p

atie

nts

bec

ause

of l

oca

l in

ject

ion

-sit

e re

acti

on

s (2

6.8%

in

Res

tyla

ne

and

39.

1%in

Zyp

last

).

Nar

ins

et a

l.,

2007

PM

ID:

1808

6061

USA

/Su

bje

cts

wit

h

app

roxi

mat

ely

sym

met

rica

l NLF

s cl

assi

fied

as

gra

de

2 o

r g

reat

er o

n M

FWS

164(

149)

6

mo

Der

mic

ol-

P35

(n

= 1

49)

Res

tyla

ne

(NA

SHA

) (n

= 1

49)

NLF

sD

erm

ico

l-P3

5: m

ean

, 1.4

8 m

l; 72

rece

ived

tou

ch-u

p

inje

ctio

ns

(0.5

9 m

l) R

esty

lan

e: m

ean

, 1.1

6 m

l; 73

rece

ived

tou

ch- u

p

inje

ctio

ns

(0.4

5 m

l)

1. M

FWS

asse

ssm

ent

2. Im

pro

vem

ent

of

at le

ast

0.5

in

the

MFW

S

3. B

lind

ed

inve

stig

ato

r G

IA e

valu

atio

n

4. S

ub

ject

GIA

ev

alu

atio

n

Loca

l ski

n re

acti

on

s: Er

yth

ema,

pai

n, s

wel

ling,

b

ruis

ing,

pru

ritu

s, in

du

rati

on

wer

e ex

pec

ted

an

d o

bse

rved

in m

ost

su

bje

cts

at o

ne

orm

ore

tim

e p

oin

ts.

Eryt

hem

a w

as t

he

mo

st fr

equ

entl

y re

po

rted

tr

eatm

ent

reac

tio

n.

Ove

rwh

elm

ing

maj

ori

ty o

f in

ject

ion

-sit

e re

acti

on

s w

ere

of 4

day

s’ d

ura

tio

n o

r les

s, w

ith

alm

ost

all

of t

hem

reso

lvin

g w

ith

in

1 w

k.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e m

easu

res

Ad

vers

e ev

ents

Nar

ins

et a

l.,

2008

PM

ID:

1854

7177

USA

/Pat

ien

ts w

ith

m

od

erat

e to

sev

ere

NLF

s

75 (6

3)

18-m

o

inte

rim

o

f a

30-m

o

stu

dy

Res

tyla

ne

Pati

ents

wer

e th

en

ran

do

miz

ed

to re

trea

tmen

t at

4.5

mo

an

d

retr

eatm

ent

of t

he

oth

er N

LF a

t 9

mo.

All

pat

ien

ts re

ceiv

ed a

n

inje

ctio

n in

bo

th N

LFs

at

the

first

vis

it, w

ith

tou

ch-

up

inje

ctio

ns

as n

eed

ed

at t

he

2 w

k fo

llow

-up

vis

it.

1. E

valu

ato

r’s

rati

ng

on

th

e W

SRS

No

alle

rgic

reac

tio

ns

wer

e re

po

rted

by

pat

ien

ts in

eit

her

tre

atm

ent

gro

up

. AEs

w

ere

rep

ort

ed b

y 33

% o

f par

tici

pan

ts. T

he

mo

st c

om

mo

n w

ere

swel

ling

(23%

) an

d/

or b

ruis

ing

(20%

) at

the

inje

ctio

n s

ite.

AEs

re

solv

ed o

ver t

ime,

an

d n

o t

reat

men

t-re

late

d A

E w

as ra

ted

as

seri

ou

s.

Nar

ins

et a

l.,

2008

PM

ID:

1854

7179

USA

/Clin

ical

evi

den

ce o

f b

ilate

ral a

gin

g d

efec

ts

in t

he

nas

ola

bia

l are

a w

ith

wri

nkl

es ra

ted

as

2 o

r gre

ater

149

6, 9

, 12

mo

D

erm

ico

l-P3

5

(n =

149

)

Res

tyla

ne

(HA

) (n

= 1

49)

Each

NLF

rece

ived

on

e fil

ler;

on

e to

uch

-up

inje

ctio

n

cou

ld b

e g

iven

aft

er 2

w

k to

ob

tain

an

op

tim

al

cosm

etic

resu

lt.

1. P

ersi

sten

ce

of n

aso

lab

ial

fold

co

rrec

tio

n

(imp

rove

men

t fr

om

bas

elin

e in

th

e M

FWS

was

at

leas

t 0.

5 p

oin

t) w

ith

D

erm

ico

l- P

35

Bef

ore

6 m

o: 5

(3.4

%) o

f Der

mic

ol-

P35;

1

(0.7

%) o

f HA

At

6 m

o: 2

(1.4

%) o

f Der

mic

ol-

P35;

1 (0

.7%

) o

f HA

On

inve

stig

ato

r exa

min

atio

n o

f su

bje

cts

at

the

9- a

nd

12-

mo

follo

w-u

p w

ere

mild

er

yth

ema

and

mild

no

du

le fo

rmat

ion

.

At

the

12 m

o fo

llow

-up,

123

su

bje

cts

elec

ted

to

hav

e a

reco

rrec

tio

n fi

ller i

nje

ctio

n;

58 c

ho

se to

rece

ive

Der

mic

ol-P

35, a

nd

65

ch

ose

to re

ceiv

e H

A. L

oca

l ad

vers

e ev

ents

occ

urr

ing

aft

er t

hes

e re

corr

ecti

on

in

ject

ion

s w

ere

11 (1

9.0%

) in

Der

mic

ol-P

35

and

th

ree

(4.6

%) i

n H

A.

No

ne

was

co

nsi

der

ed s

ever

e o

r ser

iou

s an

d a

ll w

ere

anti

cip

ated

loca

l ad

vers

e ev

ents

2. B

lind

ed

inve

stig

ato

r g

lob

al

imp

rove

men

t ra

tin

gs

On

esti

et

al.,

2009

PM

ID:

1945

4518

Ital

y/25

to 8

0 yr

wit

h

mar

ked

nas

ola

bia

l fo

lds

84 (6

8)14

day

s, 2,

4,

6 m

o

Pura

gen

(n =

84)

C

apti

qu

e (n

= 8

4)

Dep

th o

f in

ject

ion

an

d t

he

volu

me

to b

e in

ject

ed

wer

e at

th

e o

per

ato

r’s

dis

cret

ion

.

1. W

SRS

2. G

AIS

A

fter

init

ial t

reat

men

t, ad

vers

e re

acti

on

s at

in

ject

ion

po

int

wer

e 92

% fo

r Pu

rag

en a

nd

90

.3%

for C

apti

qu

e, m

ain

ly o

f a m

ild to

m

od

erat

e in

ten

sity

an

d s

ho

rt-l

ived

. Ea

ch p

atie

nt

rece

ived

Pu

rag

en in

on

e N

LF

and

Cap

tiq

ue

in t

he

con

tral

ater

al fo

ld, i

n a

to

tally

ran

do

m fa

shio

n.

Du

rin

g t

he

6-m

o fo

llow

-up

, ad

vers

e re

acti

on

s w

ere

ob

serv

ed e

xclu

sive

ly a

t th

e in

ject

ion

si

te in

14.

7% o

f Pu

rag

en p

atie

nts

an

d

11.8

% o

f Cap

tiq

ue

pat

ien

ts.

Co

mp

licat

ion

s ar

isin

g 1

4 d

ays

afte

r th

e la

st t

reat

men

t h

ad a

sim

ilar i

nci

den

ce

bet

wee

n t

he

two

pro

du

cts.

All

del

ayed

-on

set

com

plic

atio

ns

sub

sid

ed

spo

nta

neo

usl

y w

ith

in a

per

iod

of 2

mo

of

trea

tmen

t.

J Am AcAd dermAtol


Pin

sky

et a

l.,

2008

PM

ID:

1908

3502

USA

/Su

bje

cts

wit

h fu

lly

visi

ble

NLF

s 29

2 (2

80)

6, 9

mo

Ju

véd

erm

Ult

ra/

Juvé

der

m U

ltra

Pl

us

(n

= 2

92)

Zyp

last

bov

ine

colla

gen

(n

= 2

92)

1.5

ml f

or i

nit

ial t

reat

men

t, 0.

7 m

l fo

r rep

eate

d

trea

tmen

t

1. In

vest

igat

or

asse

ssm

ent

of

NLF

sev

erit

y

2. C

linic

ally

si

gn

ifica

nt

imp

rove

men

t at

9 m

o

No

ser

iou

s tr

eatm

ent-

rela

ted

AEs

wer

e re

po

rted

wit

h a

ny

of t

he

fille

rs. F

or b

oth

tr

eatm

ent

gro

up

s, m

ost

tre

atm

ent-

site

re

acti

on

s (e

.g.,

eryt

hem

a, in

du

rati

on

, p

ain

, ed

ema,

no

du

le fo

rmat

ion

, bru

isin

g,

pru

ritu

s, an

d d

isco

lora

tio

n) w

ere

mild

or

mo

der

ate

in s

ever

ity

and

did

no

t re

qu

ire

inte

rven

tio

n.

Rao

et

al.,

2005

PM

ID:

1641

6642

USA

/Pat

ien

ts u

nd

erg

oin

g

corr

ecti

on

of N

LFs

8 (8

) 12

wk

Res

tyla

ne

0.7

ml

(n =

8)

Co

ntr

alat

eral

inje

ctio

n o

f ea

ch fi

ller i

nto

th

e m

id o

r d

eep

der

mis

NLF

s

1. S

ub

ject

sa

tisf

acti

on

sc

ore

No

t re

po

rted

Hyl

afo

rm 1

.0 m

l (n

= 8

) 2.

Blin

ded

in

dep

end

ent

revi

ewer

as

sess

men

t o

f im

pro

vem

ent

Vart

ania

n e

t al

., 20

05 P

MID

: 16

0273

43

USA

/Gen

eral

po

pu

lati

on

12

(8)

120

day

s 1.

Hya

luro

nid

ase

and

sa

line

(n =

12)

2. T

hre

e d

iffer

ent

do

ses

of

hya

luro

nid

ase

Hya

luro

nid

ase

inje

cted

in

cu

tan

eou

s ar

eas

pre

vio

usl

y in

ject

ed w

ith

H

A (R

esty

lan

e)

1. S

ize

of

aug

men

tati

on

cr

eate

d b

y in

ject

ed

Res

tyla

ne

25%

of p

atie

nts

dem

on

stra

ted

loca

lized

, se

lf-lim

itin

g h

yper

sen

siti

vity

reac

tio

ns

to

inje

cted

hya

luro

nid

ase.

2. C

uta

neo

us

aug

men

tati

on

Wei

nkl

e et

al.,

20

09 P

MID

: 19

7355

19

USA

/Pat

ien

ts re

ceiv

ing

in

ject

ion

s to

th

e N

LFs

72 (7

2)

2 w

k Ju

véd

erm

, 1.6

ml

(max

imu

m) (

n =

72)

Juvé

der

m li

do

cain

e,

1.6

ml (

max

imu

m)

(n =

72)

Inje

ctio

n o

f Ju

véd

erm

an

d J

uvé

der

m P

ain

at

inje

ctio

n s

ite

in t

he

Juvé

der

m a

rm li

do

cain

e to

co

ntr

alat

eral

NLF

1. P

roce

du

ral p

ain

o

n a

n 1

1-p

oin

t sc

ale

2. N

LF s

ever

ity

at

2 w

k u

sin

g t

he

WA

S

Pain

at

inje

ctio

n s

ite

in t

he

Juvé

der

m a

rm

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f S

tud

ies,

13

Arl

ette

et

al.,

2008

PM

ID:

1854

7183

C

anad

a/Su

bje

cts

un

der

go

ing

Mo

hs’

mic

rog

rap

hic

su

rger

y fo

r b

asal

cel

l car

cin

om

a o

f th

e N

LF a

rea

16

No

t re

po

rted

Juvé

der

m

NLF

1.

An

ato

mic

al lo

cati

on

o

f in

ject

ed H

A g

el

No

t re

po

rted



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Bu

gg

e et

al.,

200

7 PM

ID:

1794

4679

N

orw

ay/H

IV-i

nfe

cted

p

atie

nts

old

er t

han

18

yr

wit

h s

ever

e n

aso

gen

ian

at

rop

hy

20 (1

9)

52 w

k R

esty

lan

e Su

bQ

, 1.5

–2.0

m

l in

eac

h c

hee

k; 1

3 p

atie

nts

als

o re

ceiv

ed a

to

uch

-up

tre

atm

ent

of

Res

tyla

ne

Sub

Q, 1

.0 m

l at

wk

4

Pati

ents

rece

ived

an

inje

ctio

n in

ea

ch c

hee

k in

th

e n

aso

gen

ian

are

a.

All

inje

ctio

ns

wer

e p

erfo

rmed

by

the

sam

e p

last

ic s

urg

eon

at

an

ou

tpat

ien

t cl

inic

.

1. T

ota

l cu

tan

eou

s th

ickn

ess

(ep

ider

mal

, d

erm

al, a

nd

su

bcu

tan

eou

s th

ickn

ess)

in t

he

nas

og

enia

n a

rea

usi

ng

sta

nd

ard

ized

u

ltra

son

og

rap

hy

Mo

st p

atie

nts

exp

erie

nce

d

som

e lo

cal s

wel

ling

an

d

ten

der

nes

s o

n t

he

first

1–3

d

ays

afte

r tre

atm

ent

and

so

me

had

loca

l red

nes

s.

2. G

AIS

sco

re

3. V

AS

sco

re

4. R

ose

nb

erg

Sel

f-Es

teem

Eig

ht

pat

ien

ts h

ad p

alp

able

lu

mp

s af

ter t

reat

men

t, o

f w

hic

h s

om

e w

ere

visi

ble

. In

th

ree

pat

ien

ts, t

he

lum

ps

wer

e st

ill p

rese

nt

at w

k 53

. O

ne

pat

ien

t re

po

rted

feve

r, re

dn

ess,

swel

ling,

an

d

vesi

cles

on

his

rig

ht

chee

k 2–

3 d

ays

afte

r tre

atm

ent.

He

reco

gn

ized

th

e ve

sicl

es a

s re

curr

ent

her

pes

zo

ster

an

d

self-

trea

ted

wit

h a

cycl

ovir.

Fo

llow

ing

th

e to

uch

-up

tr

eatm

ent,

he

had

a s

imila

r re

acti

on

(wit

ho

ut

vesi

cles

) o

n h

is le

ft c

hee

k, w

hic

h

was

reso

lved

aft

er 2

–3 d

ays

wit

ho

ut

med

ical

tre

atm

ent.

Car

ruth

ers

et a

l., 2

005

PMID

: 158

4162

6 C

anad

a/N

on

pre

gn

ant,

no

n–b

reas

t-fe

edin

g

wo

men

ag

ed 2

5–60

yr

wit

h p

rom

inen

t d

ow

ntu

rned

mo

uth

co

rner

s

15 (1

4)

1 w

k, 3

, 4.5

, 6

mo

R

esty

lan

e, 0

.44

ml

(ave

rag

e u

pp

er li

p)

and

1.4

9 m

l (av

erag

e lo

wer

lip

)

Seri

al p

un

ctu

re u

sin

g a

ad

” tec

hn

iqu

e ac

ross

th

e la

tera

l par

t o

f th

e u

pp

er a

nd

low

er

lip p

lus

intr

ader

mal

ex

ten

sio

n fr

om

eac

h

late

ral c

om

mis

sure

1. S

elf-

asse

ssm

ent

2. E

valu

atio

n b

y an

in

dep

end

ent

aest

het

ic ju

dg

e u

sin

g s

tan

dar

diz

ed

crit

eria

Pain

, red

nes

s, sw

ellin

g, lu

mp

, su

per

ficia

l ag

gre

gat

e o

f m

ater

ial,

and

can

ker s

ore

w

ere

all r

epo

rted

aft

er

inje

ctio

n b

ut

dis

app

eare

d

sho

rtly

th

erea

fter

.

Thre

e su

bje

cts

rep

ort

ed

po

stin

ject

ion

her

pes

lab

ialis

.

DeL

ore

nzi

et

al.,

2006

PM

ID: 1

6442

040

Can

ada/

Pati

ents

see

kin

g

chin

an

d/o

r ch

eek

aug

men

tati

on

wit

h n

o

aest

het

ic fa

cial

su

rger

y in

th

e p

ast

12 m

o

57

1, 3

, 6, 9

, 12

mo

R

esty

lan

e 10

.0 m

l (m

axim

um

)

Ave

rag

e in

ject

ion

of 2

.2

ml (

chee

k) a

nd

2.1

ml

(ch

in)

Sub

cuta

neo

us

and

/o

r su

pra

per

iost

eal

inje

ctio

ns

1. E

ffica

cy m

easu

red

u

sin

g t

he

five-

gra

de

GA

IS b

y th

e in

vest

igat

or a

nd

p

atie

nt

Imp

lan

tati

on

co

mp

licat

ion

s o

ccu

rred

in e

igh

t p

atie

nts

.

Thre

e p

atie

nts

had

th

eir

imp

lan

ts re

mov

ed w

ith

in

3 m

o b

ecau

se o

f ski

n

ind

ura

tio

n.

J Am AcAd dermAtol


DeL

ore

nzi

et

al.,

2009

PM

ID: 1

9207

320

Can

ada/

Gen

eral

p

op

ula

tio

n

57

1, 3

, 6, 9

, 12

mo

R

esty

lan

e Su

bQ

Mea

n v

olu

mes

inje

cted

w

ere

2.1

ml i

nto

eac

h

chee

k an

d 2

.2 m

l in

to

each

ch

in

98 c

hee

ks a

nd

16

chin

s

13 p

atie

nts

rece

ived

to

uch

-up

inje

ctio

ns

at

20 s

ites

.

1. G

AIS

ass

essm

ent

per

form

ed b

y p

atie

nt

2. G

AIS

ass

essm

ent

per

form

ed b

y in

vest

igat

or

Trea

tmen

t-re

late

d A

Es o

f p

red

om

inan

tly

mild

inte

nsi

ty

wer

e re

po

rted

in 5

8% o

f p

atie

nts

. Th

e m

ost

co

mm

on

ly

rep

ort

ed e

ven

ts w

ere

loca

l in

ject

ion

-sit

e re

acti

on

s su

ch

as s

wel

ling,

ten

der

nes

s, re

dn

ess,

bru

isin

g, p

ain

, an

d

pru

ritu

s; 2

6% re

po

rted

ski

n

ind

ura

tio

n, a

nd

19%

rep

ort

ed

imp

lan

tati

on

co

mp

licat

ion

s. 70

% o

f eve

nts

ap

pea

red

in

th

e d

ay o

f tre

atm

ent

or f

ollo

win

g d

ay. S

kin

in

du

rati

on

was

freq

uen

tly

del

ayed

on

set,

mild

inte

nsi

ty

bu

t lo

ng

last

ing,

per

sist

ing

fo

r ap

pro

xim

atel

y 4

mo

on

av

erag

e.

Den

ton

et

al.,

2007

PM

ID: 1

7418

252

Can

ada/

HIV

-po

siti

ve m

en

wit

h fa

cial

lip

oat

rop

hy;

m

ean

ag

e, 4

7.2

yr

18 (1

4)

12 m

o

Perl

ane,

2.1

ml p

er s

ide

of

the

face

N

aso

lab

ial f

old

s, su

bm

alar

reg

ion

Fa

cial

ass

essm

ent

usi

ng

p

ho

tog

rap

hy

and

se

ven

- po

int

Like

rt

scal

e

Ther

e w

ere

a to

tal o

f 17

AEs

in

14

pat

ien

ts, i

ncl

ud

ing

er

yth

ema

bey

on

d 1

wk,

d

isco

mfo

rt, p

alp

abili

ty o

f p

rod

uct

, tel

ang

iect

asia

, ec

chym

osi

s, o

ozin

g fo

llow

ing

in

ject

ion

, sev

ere

inje

ctio

n

pai

n, a

nd

hyp

erse

nsi

tivi

ty.

Du

ran

ti e

t al

., 19

98

PMID

: 986

5196

It

aly/

Pati

ents

un

der

go

ing

au

gm

enta

tio

n t

her

apy

for w

rin

kles

158

(158

) 1,

2, 4

, 8 m

o

Res

tyla

ne,

1.4

ml (

aver

age)

In

ject

ion

to t

he

mid

d

erm

is o

f th

e g

lab

ella

, N

LFs,

ora

l co

mm

issu

re,

and

/or l

ips

1. S

ub

ject

ive

asse

ssm

ent

by

ph

ysic

ian

, pat

ien

t, an

d p

ho

tog

rap

hic

m

eth

od

Swel

ling

(n =

13)

Ery

them

a (n

=

7) E

dem

a (n

= 5

) Dis

com

fort

(n

= 5

) Ten

der

nes

s (n

= 3

) B

ruis

ing

(n =

3) I

tch

ing

(n =

1)

Pain

(n =

1)

2. F

ore

ign

bo

dy

reac

tio

n

Han

et

al.,

2006

PM

ID:

1650

8353

K

ore

a/Pa

tien

ts u

nd

erg

oin

g

aug

men

tati

on

rh

ino

pla

sty

11 (6

) 12

mo

C

ult

ure

d h

um

an

fibro

bla

sts

susp

end

ed

in R

esty

lan

e, 0

.6–1

.0 m

l

Inje

ctio

n in

to t

he

sub

cuta

neo

us

laye

r of

the

nas

al d

ors

um

1. A

pp

eara

nce

of

reco

nst

ruct

ed

no

ses,

deg

ree

and

ti

me

of r

eso

rpti

on

, an

d o

ccu

rren

ce o

f co

mp

licat

ion

s

Mild

deg

ree

of d

ors

al d

evia

tio

n

in o

ne

pat

ien

t

2. P

atie

nt

sati

sfac

tio

n

usi

ng

a V

AS

form



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Jud

od

ihar

djo

et

al.,

2008

PM

ID: 1

8547

174

UK

/Gen

eral

po

pu

lati

on

25

(22)

24

hr;

4, 1

2 w

k Te

osy

al (H

A),

~0.

83 m

l p

er N

LF

Sin

gle

inje

ctio

n in

to e

ach

n

aso

lab

ial f

old

1.

WSR

S M

ild in

flam

mat

ion

2. G

AIS

3.

Clin

ical

infla

mm

atio

n

scal

es fo

r ery

them

a an

d e

dem

a as

sess

ed

by

a d

erm

ato

log

ist

4. E

ryth

ema

met

er,

asse

ssed

by

spec

tro

ph

oto

met

er

(Mex

amet

er)

5. S

kin

tem

per

atu

re,

asse

ssed

by

infr

ared

te

r 6.

Su

bje

ct d

isco

mfo

rt,

asse

ssed

by

a 10

0-m

m V

AS

Ker

sch

er e

t al

., 20

08

PMID

: 183

8461

9 G

erm

any/

Skin

typ

es I–

IV,

sag

gin

g/s

lack

enin

g

faci

al s

kin

, act

inic

el

asto

sis,

loss

of s

kin

el

asti

city

, >30

yr

20 (1

9)

4, 8

, 12,

24

wk

Res

tyla

ne,

1.0

ml

Elig

ible

pat

ien

ts re

ceiv

ed

bila

tera

l in

ject

ion

s o

f H

A in

th

e lo

wer

par

t o

f th

e ch

eeks

in t

hre

e se

ssio

ns

(sta

rt, 4

, 8 w

k)

1. P

atie

nt

sati

sfac

tio

n

2. E

last

icit

y

3. S

kin

su

rfac

e m

orp

ho

log

y

4. S

kin

th

ickn

ess

and

d

ensi

ty

No

ser

iou

s A

Es o

ccu

rred

du

rin

g

the

cou

rse

of t

he

stu

dy,

an

d n

o p

atie

nts

wit

hd

rew

b

ecau

se o

f an

AE.

Fou

r pat

ien

ts d

evel

op

ed

tran

sien

t, m

ild h

emat

om

as

afte

r in

ject

ion

.

Two

pat

ien

ts e

xper

ien

ced

te

mp

ora

ry, m

ild e

ryth

ema

afte

r in

ject

ion

(las

ted

2 w

k).

On

e p

atie

nt

dev

elo

ped

a n

od

ule

ap

pro

xim

atel

y 3

mm

in

dia

met

er a

fter

th

e se

con

d

inje

ctio

n.

Seri

al p

un

ctu

re

tech

niq

ue,

ap

pro

xim

atel

y 50

0.

02-m

l in

ject

ion

s p

er

sess

ion

Low

e et

al.,

200

6mPM

ID:

1687

5468

U

SA a

nd

UK

/Pat

ien

ts

req

ues

tin

g

aug

men

tati

on

of t

he

up

per

ch

eek

or c

hin

co

nto

ur

72 (7

2)

64 w

k R

esty

lan

e Su

bQ

, 3.9

ml

Perc

uta

neo

us

inje

ctio

n;

slo

wly

inje

cted

w

ith

pal

pat

ion

; five

to

eig

ht

inje

ctio

n

tun

nel

s cr

eate

d w

ith

d

epo

siti

on

1. P

atie

nt

and

ph

ysic

ian

sa

tisf

acti

on

Tr

ansi

ent

hem

ato

ma

dev

elo

ped

in

tw

o p

atie

nts

.

On

e p

atie

nt

had

a s

mal

l-vo

lum

e lo

cal e

xtru

sio

n o

f mat

eria

l at

th

e m

edia

l asp

ect

of o

ne

chee

k.

On

e p

atie

nt

had

so

me

mo

bili

ty

in t

he

Imp

lan

t.

J Am AcAd dermAtol


Ole

niu

s, 19

98 P

MID

: 95

0283

9 Sw

eden

/Pat

ien

ts

un

der

go

ing

so

ft-t

issu

e au

gm

enta

tio

n fo

r fac

ial

wri

nkl

es

113

(100

) 1,

2, 1

2, 2

6 w

k;

12 m

o

Res

tyla

ne

(gla

bel

lar l

ines

, m

ou

th)

NLF

s, m

ater

ial a

ng

le

wri

nkl

es, g

ener

ic fa

cial

lin

es

1. S

afet

y o

f th

e in

ject

ion

2. E

ffica

cy o

f tre

atm

ent

eval

uat

ed b

y a

VAS

fro

m 0

–100

Mo

der

ate

red

nes

s, sp

ots

, sw

ellin

g

Dis

colo

rati

on

Pain

Reu

ther

et

al.,

2009

PM

ID: 1

9730

872

Ger

man

y/H

ealt

hy

wo

men

ag

ed ≥

30 y

r wit

h lo

ss o

f sk

in e

last

icit

y

19

16 w

k R

esty

lan

e V

ital

(NA

SHA

), 1.

0 m

l at

each

of t

hre

e tr

eatm

ent

sess

ion

s

Bila

tera

l in

ject

ion

s in

lo

wer

par

t o

f th

e fa

cial

ch

eeks

12 p

aram

eter

s d

escr

ibin

g t

he

visc

oel

asti

c p

rop

erti

es o

f th

e sk

in

usi

ng

th

e su

ctio

n

cham

ber

pri

nci

ple

Fou

r pat

ien

ts d

evel

op

ed

tran

sien

t, m

ild h

emat

om

a af

ter i

nje

ctio

n.

Two

pat

ien

ts d

evel

op

ed

tem

po

rary

, mild

ery

them

a.

On

e p

atie

nt

dev

elo

ped

a

no

du

le a

pp

roxi

mat

ely

2 m

m

in d

iam

eter

th

at p

ersi

sted

fo

r ap

pro

xim

atel

y 2

wk

bef

ore

dis

app

eari

ng

wit

ho

ut

trea

tmen

t.

Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

4

Dis

tan

te e

t al

., 20

09

PMID

: 192

0733

1 It

aly/

Hea

lth

y w

om

en

wit

h m

ild to

mo

der

ate

bra

chia

l pto

sis

16

90 d

ays

Res

tyla

ne

Vit

al, 1

m

l per

ses

sio

n

per

arm

Arm

Thre

e se

ssio

ns

at in

terv

als

of

30 d

ays

(T0,

T30,

T60

)

Follo

w-u

p o

ccu

rred

at T

90.

1. H

ydra

tio

n

2. S

kin

th

ickn

ess

3. E

last

icit

y

No

un

exp

ecte

d A

Es

wer

e re

po

rted

. All

exp

ecte

d t

reat

men

t-re

late

d A

Es, s

uch

as

dis

com

fort

at

th

e in

ject

ion

si

te, b

ruis

ing,

an

d

hem

ato

ma,

wer

e o

f m

ild in

ten

sity

. No

se

rio

us

AEs

wer

e re

po

rted

.

McC

rack

en e

t al

., 20

06

PMID

: 167

1492

7 U

SA/P

atie

nts

at

nin

e A

mer

ican

So

ciet

y o

f O

ph

thal

mic

Pla

stic

an

d

Rec

on

stru

ctiv

e Su

rger

y p

ract

ices

286

(286

) N/A

R

esty

lan

e

Nas

ola

bia

l fo

lds,

0.8

ml

(n =

234

)

Mel

ola

bia

l fo

lds,

0.5

ml

(n =

54)

Verm

illio

n b

ord

er, 0

.5 m

l (n

= 1

98)

Lip

vo

lum

e en

han

cem

ent,

0.6

ml (

n =

144

)

Gla

bel

lar f

old

s 0.

3 m

l,

(n =

18)

Vari

ou

s fa

cial

loca

tio

ns:

NLF

s m

elo

lab

ial f

old

s, ve

rmill

ion

bo

rder

, lip

vo

lum

e en

han

cem

ent,

gla

bel

lar f

old

s

Phys

icia

n p

erce

pti

on

o

f pat

ien

t sa

tisf

acti

on

on

a

scal

e fr

om

1–1

0 (lo

w–h

igh

)

Loca

l co

mp

licat

ion

s o

f b

ruis

ing,

sw

ellin

g,

bu

mp

ines

s, as

ymm

etry

, an

d

red

nes

s



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Ras

pal

do,

200

8 PM

ID:

1878

8032

Fr

ance

/Pat

ien

ts

pre

sen

tin

g w

ith

ho

llow

su

bp

alp

ebra

l gro

oves

, m

alar

des

cen

t, fla

t ch

eekb

on

es, h

ollo

w

tem

po

ral a

reas

, sca

r d

epre

ssio

n, o

r ch

in

retr

usi

on

102

6–18

mo

Ju

véd

erm

Vo

lum

a,

volu

me

inje

cted

bas

ed

on

bas

elin

e vo

lum

e lo

ss

sco

re

Mid

face

reg

ion

: Su

bm

alar

/su

bp

alp

ebra

l are

a (c

entr

al

mid

face

) an

d m

alar

are

a (la

tera

l mid

face

)

1. G

AIS

inve

stig

ato

r as

sess

men

t o

f vo

lum

e re

sto

rati

on

2. In

vest

igat

or

asse

ssm

ent

of t

he

over

all

volu

miz

ing

eff

ect

3. P

atie

nt a

sses

smen

t o

f aes

thet

ic e

ffec

t

Nin

e te

mp

ora

ry A

Es

wer

e re

cord

ed in

ei

gh

t p

atie

nts

, wh

ich

la

sted

bet

wee

n 3

an

d 4

2 d

ays.

Rep

ort

ed c

ases

wer

e sw

ellin

g, h

emat

om

a,

over

corr

ecti

on

, an

d

hyp

erse

nsi

tivi

ty.

On

ly o

ne

pat

ien

t re

qu

ired

an

tiin

flam

mat

ory

m

edic

atio

n fo

r tr

eatm

ent.

Wah

l, 20

08 P

MID

: 19

1466

07

16 E

uro

pea

n c

ou

ntr

ies/

Pati

ents

inje

cted

wit

h a

re

sorb

able

der

mal

fille

r in

th

e p

revi

ou

s 18

mo

3566

N

ot

rep

ort

ed

HA

fille

r in

corp

ora

tin

g

lido

cain

e (H

AL)

; mea

n,

1.1

ml

NLF

reg

ion

1.

Inje

cto

r-as

sess

ed

ease

2. P

atie

nt-

rep

ort

ed

pai

n le

vels

(Bri

tish

Pa

in S

cale

)

3. In

ject

or-

rate

d

aest

het

ic e

ffec

t

Occ

urr

ed in

6%

of

sub

ject

s, al

l of w

hic

h

wer

e te

mp

ora

ry in

n

atu

re.

Cro

ss-S

ecti

on

al S

tud

y: N

o. o

f S

tud

ies,

1

An

dre

, 200

4 PM

ID:

1519

6154

Fr

ance

/Pat

ien

ts re

ceiv

ing

N

ASH

A in

ject

ion

s 43

20

N/A

Res

tyla

ne

Vari

ou

s N

ot

rep

ort

ed

34 c

ases

of h

yper

sen

siti

vity

reac

tio

ns

wer

e re

po

rted

wit

h 1

6 im

med

iate

se

nsi

tivi

ty a

nd

18

del

ayed

sen

siti

vity

. Pe

rlan

e N

o b

acte

rial

infe

ctio

n

Up

to 4

% in

cid

ence

of h

erp

etic

re

curr

ence

s D

isco

lora

tio

n o

f th

e sk

in if

th

e p

rod

uct

is

pla

ced

too

su

per

ficia

lly

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

39

Alij

ota

s-R

eig

et

al.,

2008

PM

ID:

1821

1407

Vari

ou

s/Pa

tien

ts w

ith

sev

ere,

d

elay

ed s

ide

effe

cts

re

late

d to

HA

- AH

25

up

to 6

0 m

o

HA

alo

ne

(n =

16)

HA

-AH

co

mp

ou

nd

s

(n =

9)

Rep

ort

s o

n 2

5 ca

ses;

pat

ien

ts w

ith

in

term

edia

te o

r del

ayed

-on

set

sid

e ef

fect

s re

late

d to

co

smet

ic/

aest

het

ic im

pla

nt

fille

rs

Ave

rag

e la

ten

cy t

ime,

13.

7 m

o (r

ang

e,

1– 6

0 m

o)

J Am AcAd dermAtol


Al-

Shra

im e

t al

., 20

07

PMID

: 177

6174

4 U

SA/6

2-yr

-old

wo

man

1

10 m

o s

ince

tre

atm

ent;

6 m

o fo

llow

ing

re

mov

al o

f no

du

le

Res

tyla

ne

Man

dib

le re

gio

n

No

t re

po

rted

1-

cm s

ub

cuta

neo

us

no

du

le o

verl

yin

g

the

low

er t

hir

d o

f th

e m

and

ible

An

war

et

al.,

2007

PM

ID: 1

7549

561

UK

/41-

yr-o

ld w

hit

e w

om

an

1 36

mo

D

erm

aLiv

e (6

0%

hya

luro

nic

aci

d)

Inje

ctio

ns

for

nas

ola

bia

l w

rin

kles

Del

ayed

sw

ellin

g a

t in

ject

ion

sit

e th

at

gra

du

ally

incr

ease

d in

siz

e

Arr

on

et

al.,

2007

PM

ID: 1

7760

694

Trea

tmen

t o

ccu

rred

in

Hu

ng

ary/

59-y

r-o

ld

Cau

casi

an w

om

an

1 1

yr

Mat

rid

ur a

nd

M

atri

gel

(N

ASH

A)

Mel

ola

bia

l fo

lds,

gla

bel

la, l

ips,

and

per

iora

l rh

ytid

es

No

t re

po

rted

2

day

s af

ter t

reat

men

t, p

atie

nt

no

ted

si

gn

ifica

nt

swel

ling

an

d p

ain

at

the

inje

ctio

n s

ites

; sw

ellin

g p

rog

ress

ed

and

5 d

ays

afte

r tre

atm

ent,

pat

ien

t w

as a

dm

itte

d to

th

e h

osp

ital

for

sig

nifi

can

t fa

cial

ed

ema.

Pa

tien

t p

rese

nte

d to

th

e au

tho

r’s c

linic

2

mo

aft

er t

reat

men

t w

ith

no

tab

le

edem

a w

ith

ery

them

a o

f th

e g

lab

ella

an

d m

elo

lab

ial f

old

s an

d

was

tre

ated

wit

h h

yalu

ron

idas

e.

Rea

ctio

n re

solv

ed c

om

ple

tely

by

1 yr

af

ter i

nje

ctio

n o

f hya

luro

nid

ase.

Bar

daz

zi e

t al

., 20

07

PMID

: 177

6069

4 It

aly/

54-y

r-o

ld w

om

an

1 2

yr 2

mo

R

esty

lan

e M

elo

lab

ial f

old

s A

fter

2 y

r of c

on

tin

uo

us,

tro

ub

le-f

ree

use

, on

e tr

eatm

ent

resu

lted

in a

g

ran

ulo

mat

ou

s re

acti

on

in t

he

mel

ola

bia

l fo

lds.

Bo

snia

k et

al.,

200

4 PM

ID: 1

5545

531

Bra

zil/

Pati

ents

un

der

go

ing

lip

au

gm

enta

tio

n a

nd

faci

al

rhyt

ide

abla

tio

n

1446

24

hr;

1 an

d 2

wk;

3, 6

, 9

mo

R

esty

lan

e, 1

.4 c

m3

(max

imu

m)

Inje

cted

su

per

ficia

l to

th

e m

idd

le

der

mal

la

yer w

ith

th

e n

eed

le

inse

rted

bev

el

up

. Fo

r lin

ear

dep

ress

ion

s, se

rial

p

un

ctu

res

wer

e co

mb

ined

w

ith

a li

nea

r th

read

ing

te

chn

iqu

e.

For b

road

er

dep

ress

ion

s, fa

nn

ing

or

cro

ss-h

atch

ing

te

chn

iqu

es

wer

e u

sed,

su

pp

lem

ente

d

wit

h s

eria

l p

un

ctu

res.

1. S

atis

fact

ion

sc

ale

(0–3

) Tr

ansi

ent

eryt

hem

a at

inje

ctio

n s

ite



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Gla

bel

lar a

rea

(n

= 1

85)

Nas

ola

bia

l fo

lds

(n

= 1

020)

O

ral c

om

mis

sure

(n

= 3

52)

Lip

s (n

= 6

85)

Inje

ctio

ns

to t

he

gla

bel

lar a

rea,

N

LFs,

ora

l co

mm

issu

re,

and

lip

s

2. P

hys

icia

n

eval

uat

ion

o

f gla

bel

lar,

NLF

s, an

d o

ral

com

mis

sure

u

sin

g t

he

4 d

egre

es

of r

hyt

ide

red

uct

ion

(0

–3)

3. P

hys

icia

n

eval

uat

ion

o

f lip

s u

sin

g

pre

trea

tmen

t/

po

sttr

eatm

ent

ph

oto

gra

ph

ic

com

par

iso

n

of v

olu

me

and

co

nto

ur

char

acte

rist

ics

(0–3

)

de

Lace

rda

et a

l.,

2007

PM

ID:

1808

6060

Bra

zil/

Two

wo

men

, ag

ed 4

5 an

d 5

2 yr

2

Cas

e 1:

1 y

r Cas

e 2:

4

mo

C

ase

1: E

vole

nce

(p

orc

ine

colla

gen

), 2

ml

Cas

e 1:

No

se, N

LFs,

and

lip

s N

ot

rep

ort

ed

Cas

e 1:

No

ne

rep

ort

ed

C

ase

2: V

olu

ma

(HA

), 2

ml

Cas

e 2:

No

se, N

LFs,

lips

Cas

e 2:

Min

imal

ed

ema

that

d

isap

pea

red

by

day

5 a

fter

tr

eatm

ent

Des

cam

ps

et a

l., 2

008

PMID

: 184

4602

9Fr

ance

/Pat

ien

ts w

ith

ch

ron

ic h

epat

itis

C

trea

ted

wit

h in

terf

ero

n

alfa

s

2C

ase

1: 5

yr a

fter

tr

eatm

ent

Cas

e 2:

2

yr a

fter

tre

atm

ent

Cas

e 1:

Un

kno

wn

p

erm

anen

t d

erm

al fi

ller

Cas

e 2:

HA

Cas

e 1:

Mes

ola

bia

l an

d n

aso

lab

ial

fold

s

Cas

e 2:

Per

ibu

ccal

an

d li

on’

s w

rin

kles

No

t re

po

rted

C

ase

1: S

arco

idal

gra

nu

lom

as p

rese

nt

in n

od

ule

s fo

un

d in

th

e le

gs,

edem

a in

th

e fa

ce w

ith

infil

trat

ed m

asse

s in

th

e m

eso

lab

ial a

nd

nas

ola

bia

l fo

lds

pre

sen

t w

ith

gra

nu

lom

as

wit

h v

acu

ola

ted

mac

rop

hag

es,

pu

lmo

nar

y fu

nct

ion

test

s re

veal

d

ecre

ase

in t

he

diff

usi

on

cap

acit

y o

f ca

rbo

n m

on

oxid

e (5

8% o

f no

rmal

va

lue)

, an

d t

ub

ercu

lin a

ner

gy

was

o

bse

rved

.

J Am AcAd dermAtol


Cas

e 2:

Ed

ema

and

infil

trat

ed n

odul

es

with

pur

pur

a in

the

lips

and

the

inje

cted

are

as; b

iop

sy c

onfir

med

fo

reig

n b

ody

gra

nulo

ma,

inte

rfer

on

and

rib

aviri

n w

ere

dis

cont

inue

d

but

late

r cirr

hosi

s w

as d

iag

nose

d

and

inte

rfer

on a

nd ri

bav

irin

wer

e g

iven

ag

ain;

pat

ient

dev

elop

ed s

icca

sy

mp

tom

s an

d e

dem

a an

d p

urp

uric

in

filtr

ated

lesi

ons

flare

d u

p a

gai

n,

bio

psy

was

typ

ical

of s

arco

idos

is;

ches

t CT

scan

dem

onst

rate

d

pul

mon

ary

sarc

oid

osis

with

ly

mp

had

enop

athy

and

mic

rono

dul

es

wer

e co

nfirm

ed b

y g

alliu

m.

Do

use

-Dea

n e

t al

., 20

08 P

MID

: 18

3802

10

USA

/Wo

men

bet

wee

n 4

3 an

d

50 y

r old

3

2 w

k–1

yr

Cas

e 1:

HA

Cas

e 2:

HA

Cas

e 3:

HA

Cas

e 1:

Mel

ola

bia

l fo

ld r

hyt

ides

Cas

e 2:

Mar

ion

ette

lin

es

Cas

e 3:

Ver

mill

ion

b

ord

er

No

t re

po

rted

C

ase

1: 1

wk

afte

r tre

atm

ent,

pat

ien

t n

ote

d a

n u

nd

esir

able

blu

e/g

ray

dis

colo

rati

on

tow

ard

th

e m

edia

l p

ort

ion

of t

he

mel

ola

bia

l fo

lds.

Cas

e 2:

Blu

ish

dis

colo

rati

on

alo

ng

m

ario

net

te li

nes

th

at d

id n

ot

sub

sid

e 1

yr a

fter

tre

atm

ent

Cas

e 3:

Pat

ien

t co

mp

lain

ed o

f blu

ish

b

um

ps

on

th

e ve

rmill

ion

bo

rder

2

wk

afte

r in

ject

ion

s.

Fern

and

ez- A

cen

ero

et

al.,

200

3 PM

ID:

1472

5668

Spai

n/4

8-yr

-old

wo

man

1

2 m

o

Res

tyla

ne

Inje

ctio

n o

f R

esty

lan

e in

u

pp

er li

p

No

t re

po

rted

D

iscr

ete

no

du

les

on

up

per

lip

Fezz

a, 2

008

PMID

: 18

3171

50

USA

/Cau

casi

an, f

air-

ski

nn

ed

pat

ien

ts w

ith

low

er e

yelid

ci

catr

icia

l ect

rop

ion

15 (n

= 7

1 y

r fe

mal

e, n

=

8 m

ale

pat

ien

ts)

1 yr

R

esty

lan

e, 1

cc

Eyel

id

Rat

e o

f su

cces

s 12

sh

ow

ed b

ruis

ing

an

d t

hre

e h

ad s

mal

l fille

r lu

mp

s th

at w

ere

trea

ted

wit

h m

assa

ge

(no

ser

iou

s co

mp

licat

ion

s).

Frie

dm

an e

t al

., 20

02

PMID

: 120

8167

7 Eu

rop

e, C

anad

a, A

ust

ralia

, So

uth

Am

eric

a, A

sia/

AEs

to

NA

SHA

406,

000

NA

N

A

Res

tyla

ne,

Per

lan

e,

Res

tyla

ne

Fin

e Li

nes

No

t re

po

rted

N

ot

rep

ort

ed

In 1

999,

222

AEs

in 1

44,0

00

pat

ient

s tr

eate

d; m

ajor

ity w

ere

hyp

erse

nsiti

vity

reac

tions

and

in

ject

ion-

site

infla

mm

atio

n; o

ther

rare

re

por

ts o

f loc

aliz

ed g

ranu

lom

atou

s re

actio

ns, b

acte

rial i

nfec

tions

, and

ac

neifo

rm a

nd c

ystic

lesi

ons.

In 2

000,

144

AEs

in 2

62,0

00 p

atie

nts

; m

ajo

rity

wer

e h

yper

sen

siti

vity

re

acti

on

s an

d in

ject

ion

-sit

e in

flam

mat

ion

; tw

o c

ases

of

inje

ctio

n-s

ite

nec

rosi

s; o

ther

rare

re

po

rts

of l

oca

lized

gra

nu

lom

ato

us

reac

tio

ns,

bac

teri

al in

fect

ion

s, an

d

acn

eifo

rm a

nd

cys

tic

lesi

on

s.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Furm

ancz

yk e

t al

., 20

09 P

MID

: 19

2073

30

USA

an

d T

hai

lan

d/5

8-yr

-old

1

(1) m

an

4- a

nd

8- w

k in

terv

als

Der

maL

ive

No

t re

po

rted

N

ot

rep

ort

ed

Vio

lace

ou

s n

od

ule

s ac

ross

fore

hea

d,

gla

bel

la, t

emp

les,

nas

ola

bia

l fo

lds,

and

mar

ion

ette

lin

es

Man

y n

od

ule

s h

ad c

om

edo

nes

, p

inp

oin

t p

ust

ule

s, an

d s

cab

s. Fo

reig

n b

od

y g

ran

ulo

mas

Gh

isla

nzo

ni e

t l.,

200

6 PM

ID: 1

6536

824

Ital

y/41

-yr-

old

wo

man

1

5 w

k–3

mo

R

esty

lan

e (H

A)

27-g

aug

e n

eed

le

lon

git

ud

inal

in

ject

ion

to

the

mel

ola

bia

l, g

lab

ella

r, an

d

per

iorb

ital

w

rin

kles

Eryt

hem

ato

us

no

du

les

dev

elo

ped

si

mu

ltan

eou

sly

at a

ll si

tes

of

inje

ctio

n 5

wk

afte

r tre

atm

ent,

sho

win

g d

ense

mu

ltin

od

ula

r in

filtr

atio

n o

f th

e d

erm

is a

nd

su

bcu

tan

eou

s fa

t.

Go

din

et

al.,

2006

PM

ID: 1

6549

735

USA

/Pat

ien

ts u

nd

erg

oin

g

faci

al s

aug

men

tati

on

10

1 (6

1)10

mo

R

adie

sse

(n =

72)

Rad

iess

e an

d

Res

tyla

ne

(n

= 2

9)

Inje

ctio

n to

th

e n

aso

lab

ial

fold

s, u

pp

er

and

low

er li

p

verm

illio

n

bo

rder

s, “l

ipst

ick

lines

,” an

d p

erio

ral

lines

Imm

edia

te a

nd

lo

ng

-ter

m

pat

ien

t sa

tisf

acti

on

su

rvey

(1

0-p

oin

t sc

ale)

No

t re

po

rted

Go

ldb

erg

et

al.,

2006

PM

ID: 1

6985

414

USA

/155

pat

ien

ts, (

41 m

en a

nd

11

4 w

om

en w

ith

ave

rag

e ag

e o

f 53

yr)

155

(121

) 6–

12 m

oR

esty

lan

e; m

ean

in

ject

ion

s w

ere:

0.

96 m

l at

first

in

ject

ion

0.8

7 m

l at

seco

nd

in

ject

ion

0.7

8 m

l at

thir

d

inje

ctio

n

Orb

ital

rim

, zy

go

mat

ic

and

sep

tal

con

fluen

ce

ho

llow

s in

th

e ti

ssu

e p

lan

e d

eep

to t

he

orb

icu

lari

s o

culi

mu

scle

Pati

ent

sati

sfac

tio

n

Bru

isin

g o

ccu

rred

in 2

2% o

f in

ject

ion

s, w

ith

9%

of i

nje

ctio

ns

resu

ltin

g in

p

atie

nts

wh

o o

bje

cted

to t

he

colo

r ch

ang

e.

Lum

ps

or c

on

tou

r irr

egu

lari

ties

are

al

mo

st u

nifo

rmly

pre

sen

t; h

ow

ever

, m

ost

pat

ien

ts fo

un

d t

he

effe

ct

acce

pta

bly

sm

oo

th.

Five

dev

elo

ped

do

ug

hy

edem

a in

th

e m

alar

are

a.

Hir

sch

et

al.,

2007

PM

ID: 1

7373

195

USA

/43-

yr-o

ld w

om

an

1 2

wk

Juvé

der

m

Mu

ltip

le d

eep

d

erm

al

inje

ctio

ns

alo

ng

th

e N

LFs

usi

ng

a li

nea

r th

read

ing

te

chn

iqu

e

48 h

r aft

er in

ject

ion

s, th

e p

atie

nt

rep

ort

ed p

ain

in t

he

trea

ted

are

a an

d h

er fa

ce “l

oo

ked

like

a p

izza

.”

J Am AcAd dermAtol


Ino

ue

et a

l., 2

008

PMID

: 183

1709

7 Ja

pan

/50-

yr-o

ld w

om

an

wit

h n

o p

rio

r co

smet

ic

surg

ery

1 43

day

s R

esty

lan

e an

d S

heb

a (c

olla

gen

)

Nas

al t

ip

(Res

tyla

ne)

an

d

up

per

lip

an

d

NLF

an

d u

pp

er

verm

ilio

n

(co

llag

en)

No

t re

po

rted

Im

med

iate

ly a

fter

th

e in

ject

ion

of

colla

gen

, th

e p

atie

nt

had

str

ikin

g

pai

n o

n t

he

left

sid

e o

f her

face

. A

few

ho

urs

late

r, sh

e n

oti

ced

re

dd

ish

dis

colo

rati

on

fro

m t

he

left

sid

e o

f th

e n

ose

an

d u

pp

er

lip to

th

e g

lab

ella

r reg

ion

, wh

ich

co

rres

po

nd

ed to

the

area

no

uri

shed

b

y th

e an

gu

lar b

ran

ch o

f th

e fa

cial

art

ery.

By

the

thir

d d

ay o

f o

nse

t, b

liste

rs h

ad a

pp

eare

d a

t th

e le

ft n

asal

ala

. Wh

en t

he

pat

ien

t co

nsu

lted

a h

osp

ital

on

th

e si

xth

d

ay, a

gan

gre

no

us

skin

nec

rosi

s m

easu

rin

g 1

× 1

.5 c

m w

as p

rese

nt

on

th

e le

ft n

asal

ala

. Th

e n

ecro

sis

exte

nd

ed to

th

e su

rro

un

din

g s

kin

an

d s

ub

cuta

neo

us

tiss

ue,

an

d w

as re

mov

ed s

urg

ical

ly

on

day

12.

A fu

ll-th

ickn

ess

skin

g

raft

tak

en fr

om

th

e p

ost

auri

cula

r ar

ea w

as g

raft

ed to

th

e re

sid

ual

sk

in d

efec

t o

n d

ay 4

3 an

d w

as

succ

essf

ully

acc

epte

d.

Jaco

no,

200

8 PM

ID:

1820

9119

U

SA/C

on

secu

tive

pat

ien

ts

pre

sen

tin

g to

a fa

cial

p

last

ic a

nd

reco

nst

ruct

ive

surg

ery

pra

ctic

e fo

r in

ject

able

lip

au

gm

enta

tio

n 66

pat

ien

ts

rece

ivin

g

137

trea

tmen

ts

9 m

o

Res

tyla

ne

Verm

ilio

n,

sub

verm

ilio

n,

per

isto

mal

, p

hilt

ral c

olu

mn

, an

d o

ral

com

mis

sure

Au

tho

rs

ind

icat

e n

ew

clas

sific

atio

n o

f lip

an

ato

mic

al

zon

es fo

r d

irec

tin

g

inje

ctio

n

Mea

n s

atis

fact

ion

sc

ore

Mea

n

per

sist

ence

u

nti

l lip

s re

turn

ed to

p

reo

per

ativ

e ap

pea

ran

ce

bae

d o

n

pat

ien

t su

bje

ctiv

e ev

alu

atio

n

No

ne

rep

ort

ed

Jham

et

al.,

2009

PM

ID: 1

9138

600

Vari

ou

s/G

ener

al p

op

ula

tio

n

56

Vari

ou

s U

pp

er/l

ow

er li

p,

NLF

, ch

eek

No

t re

po

rted

C

linic

al p

rese

nta

tio

n: S

ing

le n

od

ule

, d

iffu

se s

wel

ling,

mu

ltip

le n

od

ule

s, m

ass,

oth

er

Trea

tmen

ts: E

xcis

ion

al b

iop

sy, s

tero

ids

(sys

tem

ic a

nd

intr

ales

ion

al),

anti

bio

tics

, no

nst

ero

idal

an

tiin

flam

mat

ory

dru

gs,

uri

cosu

ric

agen

t, im

mu

no

reg

ula

tor

Jord

an, 2

005

PMID

: 16

2347

15



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e m

easu

res

Ad

vers

e ev

ents

Kan

chw

ala

et a

l.,

2005

PM

ID:

1598

5788

USA

/Pat

ien

ts u

nd

erg

oin

g

faci

al a

ug

men

tati

on

97

6 3,

6, 9

, 12

o

Au

tolo

go

us

fat

(n

= 6

97)

Hyl

afo

rm (n

= 5

2)

Res

tyla

ne

(n =

86)

Rad

iess

e

(n =

141

)

NLF

s, lip

s, g

lab

ella

1.

Typ

e o

f pro

du

ct

use

d

2. A

nat

om

ical

re

gio

n in

ject

ed

3. In

fect

ion

rate

4. T

ou

ch-u

p/

revi

sio

n ra

te

and

ove

rall

lon

gev

ity

No

t re

po

rted

Kan

e, 2

005

PMID

: 16

1516

56

USA

/24

wo

men

ag

ed

35–5

6 yr

24

10 d

ays

0.1–

0.45

ml

Res

tyla

ne

(n

= 2

3)

30-/

32-g

aug

e in

ject

ion

of

Res

tyla

ne

in t

he

low

er

eyel

id

Pati

ent

sati

sfac

tio

n

The

wo

man

to re

ceiv

e H

ylaf

orm

had

h

eavy

sw

ellin

g a

nd

dis

colo

rati

on

of

the

trea

tmen

t ar

ea fo

r 2 w

k.

Len

nox

et

al.,

2007

PM

ID: 1

7966

181

USA

/46-

yr-o

ld w

om

an

pre

sen

ted

for e

valu

atio

n o

f co

smet

ic is

sues

follo

win

g

mas

tect

om

y an

d s

ilico

ne

mp

lan

t re

con

stru

ctio

n

1 4

wk

Juvé

der

m U

ltra

, 0.

4 m

l in

to

each

nip

ple

in

each

of t

wo

tr

eatm

ent

sess

ion

s

Nip

ple

s N

ot

rep

ort

ed

No

ne

rep

ort

ed

Low

e et

al.,

200

7 PM

ID: 1

7852

625

USA

/32-

yr-o

ld w

om

an w

ith

m

ildly

atr

op

hic

up

per

lip

an

d m

elo

men

tal f

old

s

1 (1

)1

hr a

fter

tre

atm

ent

Res

tyla

ne,

1.5

cc

Fille

r was

inje

cted

in

th

e u

pp

er

lip a

nd

m

elo

men

tal

area

aft

er 1

%

lido

cain

e n

erve

b

lock

was

g

iven

for b

lock

w

as g

iven

for

anae

sth

esia

Ch

ang

e in

lip

vo

lum

e u

sin

g t

hre

e-d

imen

sio

nal

p

ho

tog

rap

hy

imag

ery

(Su

rfac

e Im

agin

g L

td

and

Can

field

Sc

ien

tific

Ve

ctra

3D

Vo

lum

etri

c A

nal

ysis

)

Loca

lized

sw

ellin

g a

s as

sess

ed b

y th

e th

ree-

dim

ensi

on

al im

ager

y

Mal

ho

tra,

200

7 PM

ID:

1807

1111

U

SA/P

atie

nts

fro

m

18–

36 y

r old

5

6–9

mo

R

esty

lan

e Su

b-Q

(H

A),

2 m

l ea

ch a

t tw

o

trea

tmen

ts

Intr

aco

nal

an

d

extr

aco

nal

p

ost

erio

r orb

it

No

t re

po

rted

O

ne

pat

ien

t re

qu

ired

hya

luro

nid

ase

for m

igra

tin

g g

el, w

hic

h c

ause

d

low

er e

yelid

sw

ellin

g; o

ne

pat

ien

t re

qu

ired

orb

ital

mag

net

ic

reso

nan

ce im

agin

g 9

mo

aft

er

inje

ctio

n, a

nd

vo

lum

etri

c an

alys

is

bas

ed o

n c

oro

nal

an

d a

xial

cu

ts.

J Am AcAd dermAtol


Nyt

e, 2

007

PMID

: 17

5808

05

USA

/50-

yr-o

ld m

an

pre

sen

ted

wit

h lo

ng

h

isto

ry o

f nas

al

ob

stru

ctio

n

12

day

s R

esty

lan

e, 0

.15

ml

Cau

dal

-med

ial

surf

ace

of t

he

up

per

late

ral

cart

ilag

e o

f th

e n

asal

val

ve

No

t re

po

rted

Min

or m

idd

le v

ault

dis

com

fort

an

d

swel

ling

or d

ays

afte

r tre

atm

ent

Up

per

late

ral

cart

ilag

e o

f th

e n

asal

val

ve

Od

un

ze e

t al

., 20

07

PMID

: 180

9076

7 U

SA/P

atie

nts

wit

h

aver

age

age

of 5

6 yr

60

(n =

45

Fitz

pat

rick

I–

III, n

= 2

0 Fi

tzp

atri

ck

IV-V

I)

6–9

mo

R

esty

lan

e In

ject

ion

s to

th

e d

erm

al-

epid

erm

al

jun

ctio

n o

f th

e N

LFs,

fore

hea

d,

gla

bel

la,

ario

net

te li

nes

, an

d s

cars

u

sin

g s

eria

l th

read

ing

; se

rial

pu

nct

ure

u

sed

at

tear

tr

ou

gh

, ch

eek,

an

d o

ral

com

mis

sure

Co

mp

aris

on

s b

etw

een

Fi

tzp

atri

ck I–

III

and

Fit

zpat

rick

IV

–VI c

oh

ort

s

Of F

itzp

atri

ck I–

III, n

o p

erm

anen

t ad

vers

e o

utc

om

es; h

ow

ever

, tw

o

pat

ien

ts h

ad t

ran

sien

t se

qu

elae

an

d o

ne

pat

ien

t h

ad id

iop

ath

ic

ang

ioed

ema

of t

he

lips

for 3

6 h

r; o

ne

pat

ien

t al

so h

ad in

clu

sio

n c

yst

that

req

uir

ed d

rain

age.

Para

da

et a

l., 2

005

PMID

: 162

7614

9 B

razi

l 11

No

t re

po

rted

R

esty

lan

e (H

A),

Met

aCri

ll (p

oly

met

hyl

-m

eth

acry

late

), A

qu

amid

(p

oly

acry

lam

ide)

, N

ew-F

ill (p

oly

lact

ic

acid

), A

rtec

oll

(po

lym

eth

yl-

met

hac

ryla

te

susp

end

ed in

a

colla

gen

so

luti

on

)

Bio

psy

sp

ecim

ens

fixed

in 1

0%

form

alin

Res

tyla

ne:

An

infla

mm

ato

ry p

roce

ss

occ

urr

ed o

n t

he

dee

p re

ticu

lar d

erm

is,

hyp

od

erm

is, a

nd

at

the

leve

l of t

he

der

mal

mu

scu

latu

re. P

eria

dn

exal

an

d

per

ivas

cula

r lym

ph

om

on

on

ucl

ear

infil

trat

es w

ere

ob

serv

ed in

th

e

sup

erfic

ial a

nd

dee

p d

erm

is, i

n

add

itio

n to

nu

mer

ou

s eo

sin

op

hils

.

Aq

uam

id: I

nfla

mm

ato

ry in

filtr

ates

wer

e

ob

serv

ed o

n t

he

dee

p re

ticu

lar d

erm

is,

hyp

od

erm

is, a

nd

der

mal

mu

scu

latu

re.

Met

aCri

ll: A

foca

l or d

iffu

se in

flam

mat

ory

infil

trat

e at

th

e re

ticu

lar d

erm

is a

nd

hyp

od

erm

is w

as o

bse

rved

.

New

-Fill

: A c

on

nec

tive

tis

sue

pre

sen

ted

diff

use

infla

mm

ato

ry in

filtr

ate.

Art

eco

ll: A

co

nn

ecti

ve fi

bro

us

and

str

iate

d

mu

scu

lar t

issu

e p

rese

nte

d w

ith

den

se

and

diff

use

infla

mm

ato

ry in

filtr

ate.

Liq

uid

Sili

con

e: F

ibri

llar c

on

nec

tive

tis

sue

pre

sen

ted

wit

h d

iffu

se in

flam

mat

ory

infil

trat

e.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Pate

l et

al.,

2006

PM

ID: 1

6651

928

USA

/65-

yr-o

ld w

om

an

11

yr

Res

tyla

ne,

0.7

-ml

syri

ng

e 30

-gau

ge

inje

ctio

ns

in

the

NLF

s, lip

s, an

d p

erio

ral

rhyt

ides

Exte

nsi

ve e

ryth

ema,

ed

ema,

an

d

ind

ura

tio

n o

f th

e in

ject

ion

reg

ion

s o

f th

e N

LFs

and

per

iora

l are

as

occ

urr

ed 1

2 w

k af

ter f

ou

rth

tr

eatm

ent.

Pete

r et

al.,

2006

PM

ID: 1

6764

658

Ger

man

y/48

-yr-

old

man

1

18 m

oR

esty

lan

eG

lab

ella

r are

a an

d

the

chee

ksO

ne

min

ute

aft

er la

st in

ject

ion

, pat

ien

t re

po

rted

par

tial

vis

ual

loss

in h

is

rig

ht

eye.

A re

tin

al b

ran

ch a

rter

y o

cclu

sio

n o

f th

e su

per

ior t

emp

le

arte

ry w

as id

enti

fied

.

Req

uen

a et

al.,

200

1 PM

ID:1

1391

099

Spai

n/5

2 yr

old

man

, 42

yr o

ld w

om

an,

2 38

yr o

ld w

om

en

46-

14 m

oA

rtec

oll

(n =

1)

Der

mal

ive

(n =

1)

Silic

on

e (n

=2)

Art

eco

ll:

Nas

ola

bia

l an

d

fore

hea

d fo

lds

Der

mal

ive:

Fo

reh

ead

an

d

per

iocu

lar

rid

ges

Silic

on

e:

Nas

ola

bia

l fo

lds,

chee

ks

Art

eco

ll: E

ryth

emat

ou

s, ri

bb

ed,

pal

pab

le in

du

rati

on

s o

f bo

th

nas

ola

bia

l an

d fo

reh

ead

s fo

lds

Der

mal

ive:

Ery

them

ato

us

pal

pab

le

ind

ura

tio

ns

on

fore

hea

d

Silic

on

e: E

ryth

emat

ou

s p

alp

able

in

du

rati

on

s o

f bo

th n

aso

lab

ial

fold

s, p

alp

able

ind

ura

tio

ns

on

bo

th

chee

ks w

ith

mild

ery

them

a

Ro

ssn

err e

t al

., 20

09

PMID

: 192

0732

7G

erm

any/

Pati

ents

tre

ated

w

ith

a m

eth

acry

late

-bas

ed

fille

r wh

o d

evel

op

ed a

re

acti

on

in t

he

sam

e ar

ea

34N

/AD

erm

aliv

e (h

ydro

xyet

hyl

-m

eth

acry

late

an

d

eth

ylm

eth

acry

late

in

a fi

xed

co

mb

inat

ion

w

ith

HA

)

Fille

rs in

ject

ed

in 9

5 ar

eas

amo

ng

th

e 34

p

atie

nts

Co

mm

on

are

as:

NLF

s (4

6.3%

) C

orn

ers

of t

he

mo

uth

(17.

9%)

Gla

bel

la

(17.

9%) U

pp

er

lip (1

2.6%

)

No

t re

po

rted

. In

th

e 34

pat

ien

ts, t

he

met

hac

ryla

te

fille

r was

inje

cted

into

95

area

s. O

f th

ese

95 a

reas

, 87

(91.

6%) s

ho

wed

a

reac

tio

n.

The

mo

st fr

equ

entl

y o

bse

rved

ad

vers

e ev

ents

wer

e th

e d

evel

op

men

t o

f n

od

ule

s (n

= 8

5), d

isco

lora

tio

n

(n =

39)

, ery

them

a o

r in

flam

mat

ion

(n

= 3

2), a

nd

sw

ellin

g (n

= 2

4). M

ost

n

od

ula

r rea

ctio

ns

wer

e ra

ted

as

seve

re.

Mea

n t

ime

of o

nse

t w

as 2

3.1

(SD

22.

8)

mo.

Sch

wei

ger

et

al.,

2008

PM

: 183

1872

6 U

SA/2

1-yr

-old

wo

man

w

ith

cle

ft li

p, p

rio

r to

tr

eatm

ent

had

rece

ived

12

reco

nst

ruct

ive

pro

ced

ure

s b

y cr

anio

faci

al s

urg

eon

s;

com

pla

ined

of l

ip

asym

met

ry

1 ~

4 m

o

Res

tyla

ne,

0.7

ml

Up

per

lip

N

ot

rep

ort

ed

No

ne

rep

ort

ed

J Am AcAd dermAtol


Sid

wel

l et

al.,

2004

PM

ID: 1

5550

141

UK

/40-

yr-o

ld w

hit

e w

om

an

wo

man

1

8, 1

2 m

o

Der

mal

ive

(syn

thet

ic

hya

luro

nic

aci

d

and

acr

ylic

h

ydro

gel

)

Inje

ctio

ns

of

Der

mal

ive

to

the

nas

ola

bia

l fo

lds

Firm

red

lin

ear l

ines

dev

elo

ped

4 m

o

afte

r pro

ced

ure

alo

ng

th

e si

tes

of

the

inje

ctio

ns.

Sop

arka

r et

al.,

2005

PM

ID: 1

5778

672

USA

/62-

yr-o

ld w

om

an

1 7

and

17

day

s, 5

mo

Tw

o 0

.7-m

l sy

rin

ges

of

Res

tyla

ne

NLF

s N

ot

rep

ort

ed

Pro

gre

ssiv

e sw

ellin

g, p

ain

, war

mth

, an

d e

ryth

ema

alo

ng

on

e o

f th

e tw

o in

ject

ion

sit

es a

fter

7 d

ays.

Pres

crib

ed m

eth

ylp

red

nis

olo

ne

over

6 d

ays.

Imm

edia

tely

aft

er

sto

pp

ing

med

icin

e, p

atie

nt

rep

ort

ed ra

pid

exa

cerb

atio

n o

f her

sy

mp

tom

s.

Tab

an e

t al

., 20

09

PMID

: 196

1778

0 U

SA/I

nfa

nts

wit

h c

on

gen

ital

ey

elid

mal

po

siti

on

s 5

(5)

Mea

n fo

llow

-up

, 11.

8 m

o

Res

tyla

ne,

0.5

ml

per

eye

lid

HA

gel

was

in

ject

ed in

sm

all a

mo

un

ts

acro

ss t

he

len

gth

of t

he

up

per

or l

ow

er

eyel

id

1. E

yelid

po

siti

on

an

d d

egre

e o

f ke

rato

pat

hy

2. D

egre

e o

f la

go

ph

thal

mo

s

Co

mp

licat

ion

s w

ere

min

or a

nd

in

clu

ded

tra

nsi

ent

ecch

ymo

sis,

edem

a, c

on

tou

r irr

egu

lari

ties

, an

d

ten

der

no

f in

ject

ion

. ess

at

the

site

s

Ove

rall,

th

ere

was

a n

on

–sta

tist

ical

ly

Sig

nifi

can

t d

ecre

ase

in m

arg

in

refle

x d

ista

nce

1 a

nd

/or m

arg

in

refle

x d

ista

nce

2, w

ith

ou

t o

bst

ruct

ion

of t

he

visu

al a

xis.

On

e p

atie

nt

had

incr

ease

d

asti

gm

atis

m o

n o

ne

sid

e (2

.00

dio

pte

rs w

ith

th

e ru

le) a

fter

tr

eatm

ent.

Varg

as- M

ach

uca

et

al.

2006

PM

ID:

1662

5084

Spai

n/5

0-yr

-old

wo

man

1

1 yr

2 m

o

Der

mal

ive

Peri

ora

l ski

n

4 m

o a

fter

inje

ctio

ns,

pat

ien

t n

ote

d

eryt

hem

ato

us

pap

ule

s th

at

pro

gre

ssiv

ely

aug

men

ted

in s

ize

and

ind

ura

ted

.

Wo

lfram

et

al.,

2006

PM

ID: 1

7135

735

Au

stri

a/Tw

o

58-y

r-o

ld w

om

en, o

ne

53-y

r-o

ld w

om

an

3 3

mo

–2 y

r N

ewfil

l, R

esty

lan

e,

Der

maL

ive

Zyg

om

atic

ar

ch, e

yelid

s, fo

reh

ead,

NLF

s, ch

eeks

Eryt

hem

ato

us

ind

ura

tio

ns

at in

ject

ion

si

tes

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D; A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

N/A

, no

t ap

plic

able

; PM

ID, P

ub

Med

iden

tific

atio

n n

um

ber

; HA

, hya

luro

nic

aci

d; U

SA, U

nit

ed S

tate

s; N

LF, n

aso

lab

ial f

old

; A

Es, a

dve

rse

even

ts; W

SRS,

Wri

nkl

e Se

veri

ty R

atin

g S

cale

; GA

IS, G

lob

al A

esth

etic

Imp

rove

men

t Sc

ale;

WA

S, W

rin

kle

Ass

essm

ent

Scal

e; V

AS,

vis

ual

an

alo

gu

e sc

ale;

NA

SHA

, no

n–a

nim

al-s

tab

ilize

d h

yalu

ron

ic

acid

; ID

-ST,

intr

ader

mal

ski

n te

st; I

gE,

imm

un

og

lob

ulin

E; R

F, ra

dio

freq

uen

cy; I

PL, i

nte

nse

pu

lsed

lig

ht;

SCH

A, s

ing

le c

ross

-lin

ked

hya

luro

nic

aci

d; D

CH

A, d

ou

ble

cro

ss-l

inke

d h

yalu

ron

ic a

cid

; CaH

A, c

alci

um

h

ydro

xyla

pat

ite;

MFW

S, M

od

ified

Fit

zpat

rick

Wri

nkl

e Sc

ale;

GIA

, Glo

bal

Imp

rove

men

t A

sses

smen

t; C

T, c

om

pu

ted

tom

og

rap

hic

; HIV

, hu

man

imm

un

od

efici

ency

vir

us;

AH

, acr

ylic

hyd

rog

el.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Co

llag

en F

iller

s R

and

om

ized

Co

ntr

olle

d T

rial

: No

. of

Stu

die

s, 1

3

Bau

man

n e

t al

., 20

07

PMID

: 180

8605

0 U

SA/S

ub

ject

s at

leas

t 30

yr

old

an

d w

ith

fully

vis

ible

b

ilate

ral N

LFs

that

wer

e ap

pro

xim

atel

y sy

mm

etri

cal

(bo

th m

od

erat

e o

r bo

th

seve

re)

439

(423

) 24

wk

HA

: Ju

véd

erm

30

(J30

), Ju

véd

erm

U

ltra

(24H

V),

Juvé

der

m U

ltra

Pl

us

(30H

V);

med

ian

, 1.6

ml

(ran

ge,

0.8

–5.6

m

l)

Zyp

last

; med

ian

, 2.

0 m

l (r

ang

e, 0

.8–7

.7

ml)

Sub

ject

s w

ere

assi

gn

ed

ran

do

mly

to

rece

ive

on

e o

f th

e th

ree

smo

oth

-gel

H

A fi

llers

, in

trad

erm

ally

to

th

e N

LF o

n

on

e si

de

the

NLF

on

on

e si

de

sub

ject

s, th

e N

LF o

n t

he

oth

er s

ide

of

the

face

was

tr

eate

d w

ith

in

terv

enti

on

, an

d la

sted

7

day

s o

r les

s. Z

ypla

st.

1. F

ive-

po

int W

AS

2. E

ffica

cy

3. P

atie

nt

sati

sfac

tio

n

Freq

uen

cy a

nd

sev

erit

y o

f tre

atm

ent-

site

reac

tio

ns

wer

e si

mila

r fo

r all

fille

rs. T

her

e w

ere

no

tre

atm

ent-

rela

ted

AEs

oth

er t

han

th

ose

lo

caliz

ed to

th

e ar

ea o

f in

ject

ion

.

In a

ll tr

eatm

ent

gro

up

s, th

e m

ajo

rity

o

f rea

ctio

ns

at t

he

trea

tmen

t si

te

wer

e m

ild to

mo

der

ate

in s

ever

ity,

d

id n

ot

req

uir

e in

terv

enti

on

, an

d la

sted

7 d

ays

or l

ess.

Ther

e w

as o

ne

sig

nifi

can

t A

E re

po

rted

: st

erile

ab

sces

s at

th

e in

ject

ion

sit

e o

ccu

rrin

g 4

mo

aft

er t

reat

men

t w

ith

b

ovin

e co

llag

en.

AE

pat

tern

s an

d in

cid

ence

wer

e si

mila

r b

etw

een

Cau

casi

an a

nd

no

n-

Cau

casi

an s

ub

ject

s.

The

vast

maj

ori

ty

of s

ub

ject

s h

ad o

nly

on

e tr

eatm

ent

visi

t.

Co

hen

et

al.,

2004

PM

ID: 1

5468

406

USA

/Pat

ien

ts a

t le

ast

18 y

r of

age

pre

sen

tin

g fo

r gla

bel

lar,

NLF

, rad

ial u

pp

er li

p li

ne,

m

ario

net

te li

ne

corr

ecti

on

251

(251

) (11

1 at

12m

o)

1, 3

, 6, 1

2 m

o

Art

eco

ll (n

= 1

28)

Zyd

erm

II o

r Z

ypla

st

(n =

123

)

Tun

nel

ing

te

chn

iqu

e:

Gla

bel

la,

NLF

s, ra

dia

l u

pp

er li

p li

nes

, m

ario

net

te

lines

1. C

osm

etic

co

rrec

tio

n

at 6

an

d 1

2 m

o u

sin

g

the

FFA

S b

y th

ree

mas

ked

o

bse

rver

s an

d

ph

ysic

ian

s

27 A

Es in

Art

eco

ll g

rou

p; 3

8 A

Es in

co

llag

en c

on

tro

l gro

up

J Am AcAd dermAtol


Co

hen

et

al.,

2006

PM

ID: 1

6936

546

USA

/Pat

ien

ts w

ith

wri

nkl

es

of t

he

gla

bel

la, n

aso

lab

ial

fold

s, ra

dia

l up

per

lip

lin

es,

and

co

rner

s o

f th

e m

ou

th;

trea

ted

wit

h P

MM

A fi

ller i

n

piv

ota

l RC

T (C

oh

en 2

004)

251

(233

) (69

4–

5 yr

) 1,

3, 6

, 12

mo

4–5

yr

Art

eFill

(am

ou

nt

no

t sp

ecifi

ed)

(n =

128

)

Co

llag

en (a

mo

un

t n

ot

spec

ified

) (n

= 1

23)

Inje

ctio

n a

t th

e g

lab

ella

, n

aso

lab

ial

fold

s, ra

dia

l u

pp

er li

p li

nes

, o

r co

rner

s o

f th

e m

ou

th

1. C

osm

etic

co

rrec

tio

n

2. P

hys

icia

n’s

asse

ssm

ent

of

succ

ess

3. F

acia

l Fo

ld

Ass

essm

ent

Scal

e ra

tin

g

4. L

on

g-t

erm

co

smet

ic

corr

ecti

on

5. P

hys

icia

n’s

asse

ssm

ent

of l

on

g-t

erm

su

cces

s

6. S

afet

y an

d A

E

1. R

edn

ess,

swel

ling

an

d lu

mp

ines

s at

th

e in

ject

ion

sit

e fo

r co

llag

en

2. 2

7 A

Es fo

r Art

eFill

vs.

38 A

Es fo

r co

llag

en

3. S

ix la

te A

Es fo

r Art

eFill

: Tw

o s

ever

e an

d fo

ur m

od

erat

e

Gri

mes

et

al.,

2009

PM

ID: 1

9735

512

USA

/Pat

ien

ts w

ith

Fit

zpat

rick

sk

in t

ypes

IV, V

, or V

I St

ud

y 1:

24

wk

160

Stu

dy

2: 1

19

Stu

dy

1: J

uvé

der

m

Ult

ra, U

ltra

Pl

us,

and

30

and

Zyp

last

co

llag

en

Stu

dy

2: H

ylaf

orm

,

Hyl

afo

rm P

lus,

and

C

apti

qu

e

Nas

ola

bia

l fo

lds

1. N

aso

lab

ial f

old

se

veri

ty

Stu

dy

1: N

o o

ccu

rren

ces

of

hyp

erse

nsi

tivi

ty o

r hyp

ertr

op

hic

sc

arri

ng,

an

d n

o in

crea

sed

in

cid

ence

of h

yper

pig

men

tati

on

o

r hyp

op

igm

enta

tio

n in

no

n-

Cau

casi

an v

s. C

auca

sian

su

bje

cts

Stu

dy

2: N

o o

ccu

rren

ce o

f ke

loid

form

atio

n, h

yper

tro

pic

sc

arri

ng,

hyp

op

igm

enta

tio

n, o

r h

yper

sen

siti

vity

, an

d t

hre

e in

stan

ces

of m

ild h

yper

pig

men

tati

on

Lin

dq

vist

et

al.,

2005

PM

ID: 1

5622

265

No

rway

an

d S

wed

en/P

atie

nts

w

ith

pro

min

ent

NLF

s 68

(43)

2,

4, 6

, 9, 1

2 m

o

Perl

ane

(n =

68)

(o

ne

NLF

)

Zyp

last

(n =

68)

(c

on

tral

ater

al

(NLF

)

Intr

ader

mal

in

ject

ion

to

the

nas

ola

bia

l fo

lds

1. W

SRS

2. G

AIS

On

ly m

ino

r AEs

at

6 m

o a

nd

no

ne

at

12 m

o

Lup

o e

t al

., 20

08

PMID

: 181

7623

3 U

SA/S

ub

ject

s p

rese

nti

ng

w

ith

sev

ere

NLF

rate

d

as 3

or a

bov

e

87 (8

2)

4, 8

, 12,

16,

20,

24,

48

wk

Juvé

der

m U

ltra

Pl

us

(HA

) 1.7

m

l fo

r in

itia

l tr

eatm

ent,

0.6

ml f

or r

epea

ted

tr

eatm

ent

Sub

ject

s ra

nd

om

ized

to

trea

tmen

t w

ith

Ju

véd

erm

Ult

ra

Plu

s in

on

e N

LF

and

Zyp

last

in

the

op

po

site

N

LF.

1. E

ffica

cy, i

nit

ial

trea

tmen

t p

erio

d

Occ

urr

ence

of t

reat

men

t-si

te re

acti

on

s w

as s

imila

r fo

r Ju

véd

erm

Ult

ra P

lus

and

Zyp

last

.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Zyp

last

(bov

ine

colla

gen

) 70

(81%

) of

sub

ject

s re

turn

ed fo

r co

mp

limen

tary

re

pea

ted

tr

eatm

ent

wit

h J

uvé

der

m

Ult

ra P

lus,

per

form

ed

bet

wee

n 2

4 an

d 3

6 w

k

2. P

atie

nt

satis

fact

ion,

in

itial

tr

eatm

ent

per

iod

3. E

ffica

cy,

rep

eate

d

trea

tmen

t p

erio

d

Maj

ori

ty o

f in

div

idu

al re

acti

on

s la

sted

n

o m

ore

th

an 7

day

s, w

ere

mild

or

mo

der

ate

in s

ever

ity,

an

d re

qu

ired

n

o fu

rth

er in

terv

enti

on

.

Exam

ple

s: Er

yth

ema,

ind

ura

tio

n, p

ain

, ed

ema,

no

du

le, b

ruis

ing,

pru

ritu

s, an

d d

isco

lora

tio

n

Man

et

al.,

2008

PM

ID: 1

8430

173

Can

ada/

Fem

ale

pat

ien

ts w

ho

d

emo

nst

rate

d d

erm

al

thin

nin

g o

f th

e d

ors

al

han

ds

10 (1

0)

1 w

k, 1

, 3, 6

mo

R

esty

lan

e (H

A),

1.4

ml (

n =

10)

Co

smo

pla

st

(co

llag

en),

2.0

ml (

n =

10)

Pati

ents

wer

e ra

nd

om

ized

to

rece

ived

tw

o

vial

s to

eit

her

th

eir r

igh

t o

r lef

t h

and

. Tw

o v

ials

of

colla

gen

wer

e ad

min

iste

red

in

to t

he

con

tral

ater

al

han

d.

1. T

ole

rab

ility

(0

–3)

2. P

atie

nt

sati

sfac

tio

n

(1–5

)

3. C

lear

ance

Sc

ore

(1–5

), as

sess

ed b

y fo

ur b

lind

ed

ind

epen

den

t b

oar

d-c

erti

fied

in

vest

igat

ors

Ad

vers

e si

de

effe

cts

rep

ort

ed w

ith

in

ject

ion

s in

clu

din

g p

ain

, tin

glin

g,

and

bru

isin

g

On

e p

atie

nt

exp

erie

nce

d a

no

du

le

form

atio

n a

t th

e co

llag

en in

ject

ion

si

te t

hat

reso

lved

by

6 m

o.

Mo

nst

rey

et a

l., 2

007

PMID

: 175

7257

9 B

elg

ium

an

d Is

rael

/Pat

ien

ts

wit

h c

linic

al e

vid

ence

of

bila

tera

l ag

ing

def

ects

in

the

nas

ola

bia

l gra

de

scal

e:

clas

s 0

= n

on

e, a

rea

gra

de

scal

e: c

lass

0 =

no

ne,

1218

mo

Ev

ole

nce

, 1.7

2 m

l

Zyp

last

, 1.7

2 m

l

NLF

s Th

e w

rin

kle

seve

rity

in t

he

nas

ola

bia

l are

a w

as s

core

d b

y th

e tw

o s

tud

y p

hys

icia

ns

and

b

y th

e p

atie

nts

o

n a

fou

r- c

lass

1

= fi

ne,

cla

ss

2 =

fin

e to

m

od

erat

e,

and

cla

ss 3

=

mo

der

ate

to

dee

p.

A to

tal o

f 13

AEs

wer

e re

po

rted

. No

ne

was

rela

ted

to s

tud

y d

evic

es. E

igh

t o

f th

e A

Es w

ere

mild

an

d t

he

oth

er

five

wer

e o

f mo

der

ate

seve

rity

.

AEs

incl

ud

ed h

yper

sen

siti

vity

no

t re

late

d to

th

e in

vest

igat

ion

al

pro

du

ct, g

astr

oen

teri

tis,

her

pes

si

mp

lex,

uri

nar

y tr

act

infe

ctio

n,

first

-deg

ree

bu

rn, l

imb

inju

ry,

ten

do

nit

is, c

hee

k p

apu

lae,

nas

al

op

erat

ion

, var

ico

se v

ein

op

erat

ion

, an

d h

yper

ten

sio

n.

The

thre

e b

lind

ed a

sses

sors

use

d

the

valid

ated

Mo

difi

ed F

itzp

atri

ck

Wri

nkl

e Sc

ale,

a s

even

-gra

de

scal

e:

clas

s 0

= n

o w

rin

kle,

cla

ss 1

= fi

ne

wri

nkl

e, c

lass

2 =

mo

der

ate

wri

nkl

e,

and

cla

ss 3

= d

eep

wri

nkl

e, w

ith

th

ree

add

itio

nal

inte

rmed

iate

sco

res

of 0

.5, 1

.5, a

nd

2.5

.

J Am AcAd dermAtol


Nar

ins

et a

l., 2

003

PMID

: 127

8670

0 U

SA/C

orr

ecti

on

of N

LFs

138

(138

) 2,

4, 6

mo

R

esty

lan

e (n

= 1

38)

Zyp

last

(n =

138

)

Inje

ctio

n o

f eac

h

mat

eria

l to

co

ntr

alat

eral

N

LFs

1. W

SRS

2. G

AIS

Trea

tmen

t-re

late

d A

Es w

ere

rep

ort

ed

in 3

8.4%

of p

atie

nts

bec

ause

of

loca

l in

ject

ion

-sit

e re

acti

on

s (2

6.8%

in

Res

tyla

ne

and

39.

1%in

Zyp

last

).

Nar

ins

et a

l., 2

008

PMID

: 185

4717

9 U

SA/C

linic

al e

vid

ence

of

bila

tera

l ag

ing

def

ects

in

the

nas

ola

bia

l are

a w

ith

w

rin

kles

rate

d a

s 2

or

gre

ater

149

6, 9

, 12

mo

D

erm

ico

l-P3

5

(n =

149

) R

esty

lan

e (H

A)

(n =

149

)

Each

NLF

rece

ived

o

ne

fille

r, o

ne

tou

ch-u

p

inje

ctio

n c

ou

ld

be

giv

en a

fter

2

wk

to o

bta

in

an o

pti

mal

co

smet

ic re

sult

1. P

ersi

sten

ce

of n

aso

lab

ial

fold

co

rrec

tio

n

(imp

rove

men

t fr

om

bas

elin

e in

th

e M

FWS

was

at

leas

t 0.

5 p

oin

t) w

ith

D

erm

ico

l-P3

5

Prio

r to

6 m

o: 5

(3.4

%) o

f Der

mic

ol-

P35;

1

(0.7

%) o

f HA

A

t 6

mo

: 2 (1

.4%

) of D

erm

ico

l-P3

5; 1

(0

.7%

) of H

A

On

inve

stig

ato

r exa

min

atio

n o

f su

bje

cts

at t

he

9- a

nd

12

mo

follo

w-

up

wer

e m

ild e

ryth

ema

and

mild

n

od

ule

form

atio

n.

At

the

12-m

o fo

llow

-up

, 123

su

bje

cts

elec

ted

to h

ave

a re

corr

ecti

on

fil

ler i

nje

ctio

n; 5

8 ch

ose

to re

ceiv

e D

erm

ico

l- P

35, a

nd

65

cho

se to

re

ceiv

e H

A. L

oca

l AEs

occ

urr

ing

af

ter t

hes

e re

corr

ecti

on

inje

ctio

ns

wer

e 11

(19.

0%) i

n D

erm

ico

l-P3

5,

and

th

ree

(4.6

%) i

n H

A. N

on

e w

as

con

sid

ered

sev

ere

or s

erio

us

and

all

wer

e an

tici

pat

ed lo

cal A

Es.

2. B

lind

ed

inve

stig

ato

r g

lob

al

imp

rove

men

t ra

tin

gs

Scla

fan

i et

al.,

2001

PM

ID: 1

1368

660

USA

/Pat

ien

ts n

ot

alle

rgic

to

bov

ine

colla

gen

10

(10)

1,

3, 6

, 9, 1

2 m

o

Allo

Der

m, 5

.0 m

m

(n =

10)

Zyp

last

, 0.5

ml

(n =

10)

Allo

Der

m p

lace

d

surg

ical

ly in

a

sub

der

mal

p

lan

e in

on

e p

ost

auri

cula

r cr

ease

Zyp

last

inje

cted

in

a s

ub

der

mal

p

lan

e in

th

e o

pp

osi

te

po

stau

ricu

lar

crea

se

1. V

olu

me

2. H

isto

log

ic

anal

ysis

No

t re

po

rted



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Scla

fan

i et

al.,

2002

PM

ID: 1

2437

432

USA

/Pat

ien

ts w

ith

ag

e-

rela

ted

ch

ang

es in

th

e

size

an

d c

on

tou

r of t

he

lip

44 (4

4)

3, 6

, 9, 1

2 m

o

Cym

etra

(n =

19)

Zyp

last

(n =

25)

Inje

ctio

n to

th

e u

pp

er li

p

bet

wee

n t

he

orb

icu

lari

s o

ris

mu

scle

an

d

the

over

lyin

g

mu

cocu

-ta

neo

us

jun

ctio

n o

f th

e u

pp

er li

p

1. C

han

ges

in

the

nas

ola

bia

l an

gle

2. P

erce

nta

ge

of

the

tota

l lip

ac

cou

nte

d

for b

y th

e ex

po

sed

red

lip

in t

he

mid

line

and

on

th

e la

tera

l vie

w

3. V

isib

le re

d

up

per

an

d

low

er li

p

surf

ace

area

s

4. A

nte

rio

r p

roje

ctio

n o

f th

e u

pp

er a

nd

lo

wer

lip

s

No

sig

nifi

can

t lo

cal o

r sys

tem

ic

com

plic

atio

ns

Smit

h e

t al

., 20

07

PMID

: 180

8604

8 U

SA/P

ote

nti

al s

ub

ject

s w

ere

req

uir

ed to

hav

e sy

mm

etri

c,

mo

der

ate

to d

eep

NLF

s

117

(113

) 1,

3, 6

mo

R

adie

sse

(Co

llag

en)

Co

smo

pla

st

(CaH

A)

Each

sid

e w

as

trea

ted

unt

il, in

th

e ju

dg

men

t of

the

inve

stig

ator

, an

op

timal

resu

lt

was

ach

ieve

d.

At 2

wk

afte

r tr

eatm

ent,

sub

ject

s co

uld

re

ceiv

e to

uch-

up in

ject

ions

at

the

dis

cret

ion

of

the

phy

sici

an.

Occ

urre

d a

t 2-

wk

inte

rval

s, m

axim

um o

f tw

o ad

diti

onal

tr

eatm

ent

sess

ions

. Q

ualif

ying

su

bje

cts

rece

ived

CaH

A

pro

duc

t on

one

sid

e, a

nd th

e H

C p

rod

uct o

n

the

othe

r.

1. N

um

ber

of

inje

ctio

n

sess

ion

s re

qu

ired

: B

asel

ine

on

ly

2. M

ean

ch

ang

e in

LRS

fro

m

bas

elin

e, a

t 6

mo

3. S

ub

ject

-by-

sub

ject

dir

ect

com

par

iso

n, a

t 6

mo

4. G

AIS

sco

re o

f Im

pro

ved,

M

uch

Im

pro

ved,

or

Very

Mu

ch

Imp

rove

d

5. In

vest

igat

or

and

su

bje

ct

pre

fere

nce

Safe

ty a

nal

ysis

incl

ud

ed a

ll 11

7 su

bje

cts.

Co

nsi

sten

t w

ith

oth

er in

ject

able

fille

r cl

inic

al s

tud

ies,

eryt

hem

a, e

dem

a,

and

ecc

hym

ose

s w

ere

som

e o

f th

e m

ost

co

mm

on

pro

du

ct-r

elat

ed

AEs

. Bo

th e

dem

a an

d b

ruis

ing

wer

e si

gn

ifica

ntl

y m

ore

co

mm

on

on

C

aHA

- tre

ated

sid

es t

han

th

e H

C

sid

e (p

< 0

.001

). Th

ese

reac

tio

ns

last

ed a

pp

roxi

mat

ely

1 w

k af

ter

any

inje

ctio

n. M

ean

du

rati

on

for

eryt

hem

a w

as 2

–3 w

k, w

ith

no

si

gn

ifica

nt

diff

eren

ce b

etw

een

th

e tw

o t

reat

men

ts.

CaH

A: O

ne

no

du

le; H

C: t

hre

e n

od

ule

s. N

o g

ran

ulo

mas

, alle

rgie

s, u

lcer

atio

ns

or o

ther

ser

iou

s ad

vers

e ev

ents

wer

e n

ote

d.

J Am AcAd dermAtol


Co

ntr

olle

d C

linic

al T

rial

: No

. of

Stu

die

s, 2

Scla

fan

i et

al.,

2000

PM

ID:

1092

5424

U

SA/P

atie

nts

un

der

go

ing

fa

cial

aes

thet

ic s

urg

ery

wit

h s

kin

exc

isio

n

5 (3

) 2,

4, 1

2 w

k A

uto

log

en, 0

.5 m

l (n

= 5

)

Zyp

last

, 0.5

ml (

n =

5)

Two

inje

ctio

ns

of e

ach

mat

eria

l co

ntr

alat

eral

ly to

th

e p

ost

auri

cula

r are

a

1.C

linic

al

per

sist

ence

2. H

ost

tis

sue

inva

sio

n

No

t re

po

rted

.

Scla

fan

i et

al.,

2002

PM

ID:

1218

7346

U

SA/H

ealt

hy

adu

lts

20 (1

7)

4, 1

2 w

k D

erm

alo

gen

, 0.1

ml (

n =

20)

Zyp

last

, 0.1

ml (

n =

20)

Inje

ctio

n b

ehin

d t

he

con

tral

ater

al e

ar

1. P

ersi

sten

ce

2. H

isto

log

ic

iden

tific

atio

n

Infla

mm

ato

ry c

ells

wer

e id

enti

fied

at

4 w

k in

12

Der

mal

og

en a

nd

19

Zyp

last

pat

ien

ts.

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f S

tud

ies,

1

Sho

shan

i et

al.,

2007

PM

ID: 1

8086

053

USA

/Gen

eral

po

pu

lati

on

53

0 30

min

, 72

hr,

30

day

s

Evo

len

ce,

0.1

ml

Enro

lled

su

bje

cts

rece

ived

an

in

trad

erm

al in

ject

ion

in t

he

left

fo

rear

m a

nd

a s

eco

nd

inje

ctio

n in

th

e ri

gh

t fo

rear

m a

fter

2 w

k.

1. F

ollo

w-u

p s

kin

stu

dy

asse

ssm

ents

2. S

eru

m a

nti

colla

gen

an

tib

od

y d

eter

min

atio

ns

3. H

yper

sen

siti

vity

95 a

dve

rse

even

ts w

ere

reco

rded

in

62

sub

ject

s; 1

7 (1

7.9%

) wer

e co

nsi

der

ed re

late

d to

imp

lan

ts.

All

wer

e lo

caliz

ed to

imp

lan

t si

tes,

mild

in n

atu

re, a

nd

tra

nsi

ent.

Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

1

Bo

ulle

et

al.,

2009

PM

ID:

1928

8692

B

elg

ium

, Sw

eden

/Pat

ien

ts

wh

o h

ad u

nd

erg

on

e D

erm

ico

l-P3

5 30

G li

p

inje

ctio

ns

Safe

ty: 5

7

Effic

acy:

51

4–10

mo

D

erm

ico

l-P3

5 30

G

Dat

a co

llect

ed fr

om

pat

ien

ts to

en

han

ce o

r res

tore

th

e co

nto

ur

of t

he

up

per

an

d/o

r lo

wer

lip

in

eit

her

th

e ve

rmill

ion

bo

rder

, th

e b

od

y o

f th

e lip

, or b

oth

.

1. In

vest

igat

or a

sses

smen

t2.

Inve

stig

ato

r sat

isfa

ctio

n

At

lon

g-t

erm

follo

w-u

p, 9

5%

of p

atie

nts

exp

erie

nce

d n

o

swel

ling,

100

% e

xper

ien

ced

n

o b

ruis

ing,

88%

ex

per

ien

ced

no

lum

pin

ess,

and

100

% e

xper

ien

ced

n

o p

ain

ass

oci

ated

wit

h

trea

tmen

t. W

hen

pre

sen

t, lu

mp

ines

s w

as a

sses

sed

as

very

slig

ht

or w

ell-

defi

ned

, n

ot

mo

der

ate

or s

ever

e.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

17

Bra

un

et

al.,

2008

PM

ID:

1856

1590

U

SA/F

emal

e p

atie

nts

p

rese

nti

ng

to c

linic

fo

r lip

en

han

cem

ent

or a

ug

men

tati

on

20

1 yr

Ev

ole

nce

, 1.0

ml

Bo

dy

of l

ip, m

assa

ge

tech

niq

ue

use

d

imm

edia

tely

aft

er

inje

ctio

n

No

t re

po

rted

Th

ere

wer

e n

o A

Es im

med

iate

ly

afte

r tre

atm

ent.

Wit

hin

3 w

k, p

atie

nts

co

nta

cted

cl

inic

exp

ress

ing

co

nce

rn o

ver

“bu

mp

s” in

th

eir l

ips;

exa

min

atio

n

ind

icat

ed s

ub

cuta

neo

us

no

du

les

vary

ing

in s

ize

fro

m 2

to 5

mm

in

16

pat

ien

ts; n

od

ule

s w

ere

firm

an

d s

ligh

tly

yello

w in

co

lor.

On

e p

atie

nt

dev

elo

ped

fou

r cys

tic

pu

stu

les

in h

er li

ps

that

en

clo

sed

a

yello

w, p

uru

len

t m

ater

ial.

Ove

r 1 y

r lat

er, s

ix p

atie

nts

sti

ll h

ad

no

du

les

in t

hei

r lip

s.

de

Lace

rda

et a

l., 2

007

PMID

: 18

0860

60

Bra

zil/

Two

wo

men

, ag

ed

45 a

nd

52

yr

2 C

ase

1: 1

yr C

ase

2: 4

mo

C

ase

1: E

vole

nce

(p

orc

ine

colla

gen

), 2

ml

Cas

e 2:

Vo

lum

a (H

A),

2 m

l

Cas

e 1:

No

se, N

LFs,

and

lip

s

Cas

e 2:

No

se, N

LFs,

and

lip

s

No

t re

po

rted

C

ase

1: N

on

e re

po

rted

Cas

e 2:

Min

imal

ed

ema

that

d

isap

pea

red

by

day

5 a

fter

tr

eatm

ent

Fisc

her

et

al.,

2007

PM

ID:

1743

8184

G

erm

any/

48-y

r-o

ld

wo

man

1

10 y

r A

rtec

oll

Inje

ctio

ns

in t

he

up

per

an

d lo

wer

lip

s, n

aso

lab

ial

gro

oves

, an

d

gla

bel

la

Trea

tmen

t fo

r ch

ron

ic h

epat

itis

C

infe

ctio

n w

ith

peg

inte

rfer

on

al

fa-2

a an

d o

ral r

ibav

irin

in

sam

e in

ject

ion

sit

e as

Art

eco

ll in

ject

ion

s 10

yr p

rio

r res

ult

ed in

p

rog

ress

ivel

y d

isfig

uri

ng

faci

al

edem

a.

Ho

pki

ns

et a

l. 20

09 P

MID

: 19

2608

92

UK

/41

wo

men

an

d 1

7 m

en; m

ean

ag

e, 3

6 yr

58

Min

imu

m

follo

w-u

p w

as

6 m

o, w

ith

40

un

der

go

ing

fu

rth

er

revi

ew a

t 12

m

o a

nd

31

at

24 m

o

Perm

aco

l (ac

ellu

lar

cro

ss- l

inke

d p

orc

ine

der

mal

co

llag

en)

Nas

al re

gio

n d

uri

ng

rh

ino

pla

sty

No

t re

po

rted

O

ne

case

of p

ost

op

erat

ive

infe

ctio

n;

it is

no

t cl

ear w

het

her

th

is w

as

dir

ectl

y re

late

d to

th

e u

se o

f Pe

rmac

ol,

wh

ich

has

no

t n

eed

ed

rem

oval

.

On

e ca

se o

f ste

rile

cys

t fo

rmin

g o

ver

gra

ft 1

yr a

fter

tre

atm

ent

Two

pat

ien

ts re

qu

ired

min

or

revi

sio

n fr

om

a c

osm

etic

p

ersp

ecti

ve.

J Am AcAd dermAtol


Ino

ue

et a

l., 2

008

PMID

: 18

3170

97

Jap

an/5

0-yr

-old

wo

man

w

ith

no

pri

or

cosm

etic

su

rger

y

1 43

day

s R

esty

lan

e an

d S

heb

a (c

olla

gen

) N

asal

tip

(Res

tyla

ne)

an

d u

pp

er li

p

and

NLF

an

d

up

per

ver

mili

on

(c

olla

gen

)

No

t re

po

rted

Im

med

iate

ly a

fter

th

e in

ject

ion

o

f co

llag

en, t

he

pat

ien

t h

ad

stri

kin

g p

ain

on

th

e le

ft s

ide

of

her

face

. A fe

w h

ou

rs la

ter,

she

no

tice

d re

dd

ish

dis

colo

rati

on

fr

om

th

e le

ft s

ide

of t

he

no

se

and

up

per

lip

to t

he

gla

bel

lar

reg

ion

, wh

ich

co

rres

po

nd

ed

to t

he

area

no

uri

shed

by

the

ang

ula

r bra

nch

of t

he

faci

al

arte

ry. B

y th

e th

ird

day

of o

nse

t, b

liste

rs h

ad a

pp

eare

d a

t th

e le

ft n

asal

ala

. Wh

en t

he

pat

ien

t co

nsu

lted

a h

osp

ital

on

th

e si

xth

d

ay, a

gan

gre

no

us

skin

nec

rosi

s m

easu

rin

g 1

× 1

.5 c

m w

as

pre

sen

t o

n t

he

left

nas

al a

la.

The

nec

rosi

s ex

ten

ded

to

the

surr

ou

nd

ing

ski

n a

nd

su

bcu

tan

eou

s ti

ssu

e, a

nd

was

re

mov

ed s

urg

ical

ly o

n t

he

twel

fth

day

. A fu

ll-th

ickn

ess

skin

gra

ft t

aken

fro

m t

he

po

stau

ricu

lar a

rea

was

gra

fted

to

the

resi

du

al s

kin

def

ect

on

day

43

and

was

su

cces

sfu

lly a

ccep

ted

.

Jham

et

al.,

2009

PM

ID: 1

9138

600

Vari

ou

s/G

ener

al

po

pu

lati

on

56

Va

rio

us

Up

per

/lo

wer

lip

, NLF

, ch

eek

No

t re

po

rted

C

linic

al p

rese

nta

tio

n: S

ing

le n

od

ule

, d

iffu

se s

wel

ling,

mu

ltip

le

no

du

les,

mas

s, o

ther

Trea

tmen

ts: E

xcis

ion

al b

iop

sy,

ster

oid

s (s

yste

mic

an

d

intr

ales

ion

al),

anti

bio

tics

, n

on

ster

oid

al a

nti

infla

mm

ato

ry

dru

gs,

uri

cosu

ric

agen

t, im

mu

no

reg

ula

tor

Kim

et

al.,

2004

PM

ID:

1505

6148

K

ore

a/W

om

an w

ith

A

rtec

oll

trea

tmen

t fo

r n

eck

wri

nkl

es

1 4

yr

Art

eco

ll N

ot

rep

ort

ed

No

t re

po

rted

A

rtec

oll-

ind

uce

d fo

reig

n g

ran

ulo

ma

(ski

n- c

olo

red

pla

qu

es) i

n t

he

nec

k

Lan

dau

, 200

8 PM

ID:

1838

0205

Is

rael

/Fem

ale

pat

ien

ts

wit

h a

n a

vera

ge

age

of 5

2.3

yr

15

6 m

o

Evo

len

ce B

reez

e (p

orc

ine

colla

gen

-d

eriv

ed d

erm

al fi

ller)

, 1.

4 m

l

Lip

an

d n

aso

lab

ial

fold

s Pa

tien

t re

po

rted

sa

tisf

acti

on

wit

h

resu

lts.

Min

imal

sw

ellin

g w

as n

ote

d a

fter

in

ject

ion

; tra

nsi

ent

lum

pin

ess

ob

serv

ed in

itia

lly, i

t d

isap

pea

red

sp

on

tan

eou

sly

by

wk

4.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Lom

bar

di e

t al

., 20

04 P

MID

: 14

7201

98

Fran

ce/P

atie

nts

wit

h

Art

eco

ll, D

erm

aliv

e,

New

-Fill

, or L

iqu

id-

Silic

on

e–in

du

ced

g

ran

ulo

mas

11

No

t re

po

rted

A

rtec

oll

D

erm

aliv

e

New

-Fill

Liq

uid

-Si

lico

ne

No

t re

po

rted

N

ot

rep

ort

ed

12 b

iop

sy s

pec

imen

s ta

ken

: lip

s

(n =

6),

chee

ks (n

= 2

) nas

ola

bia

l fo

lds

(n =

1),

gla

bel

la (n

= 2

), an

d

low

er e

yelid

(n =

1).

All

wer

e ei

ther

CFB

Gs

or C

MG

s.

All

lesi

on

s w

ere

asym

pto

mat

ic.

Diff

eren

t ty

pes

of C

FBG

s w

ere

rela

ted

to v

ario

us

fille

rs:

Typ

e 1:

Art

eco

ll o

r Art

epla

stTy

pe

2: D

erm

aliv

e Ty

pe

3: N

ew-F

ill

Typ

e 4:

Bio

pla

stiq

ue.

CM

Gs

wer

e as

soci

ated

wit

h

Liq

uid

- Sili

con

e in

ject

ion

s.

Luu

et

al.,

2007

PM

ID:

1732

1875

U

SA/P

atie

nts

wh

o

un

der

wen

t la

ryn

go

pla

sty

bet

wee

n 1

997

and

20

06

895

No

t re

po

rted

Z

ypla

st

Para

glo

ttic

co

mp

artm

ent

of

the

voca

l fo

lds

Safe

ty o

f bov

ine

cro

ss- l

inke

d

colla

gen

in

pat

ien

ts w

ho

are

ta

kin

g w

arfa

rin

an

d a

lso

in

pat

ien

ts w

ith

ou

t p

rio

r ski

n

hyp

erse

nsi

tivi

ty

test

ing

No

ne

rep

ort

ed

Mo

od

y et

al.,

200

0 PM

ID:

1105

0497

U

SA/5

4-yr

-old

wh

ite

wo

man

1

2 m

o

1 cc

Der

mal

og

en

(hu

man

co

llag

en)

30-g

aug

e n

eed

le te

st

inje

ctio

n in

vo

lar

fore

arm

Test

inje

ctio

n in

fore

arm

resu

lted

in

an

ery

them

ato

us

8-m

m

ind

ura

ted

pap

ule

1 m

o a

fter

in

ject

ion

. On

e m

on

th la

ter,

the

sym

pto

ms

had

su

bsi

ded

.

Mo

od

y et

al.,

200

1 PM

ID:

1155

3165

U

SA/4

5-yr

-old

wo

man

1

7 w

k Z

yder

m II

(bov

ine

colla

gen

) M

ento

lab

ial c

reas

e,

chin

, lip

s N

ot

rep

ort

ed

21 d

ays

afte

r tre

atm

ent,

pat

ien

t re

po

rted

red

nes

s, sw

ellin

g, a

nd

p

ruri

tus

at t

reat

men

t si

tes.

Pove

da

et a

l., 2

006

PMID

: 16

3882

85

Spai

n/5

5-yr

-old

wo

man

,72

-yr-

old

wo

man

,70

-yr-

old

wo

man

,54

-yr-

old

wo

man

,43

-yr-

old

wo

man

5 1

mo

B

otu

linu

m to

xin

typ

e A

(B

oto

x) (n

= 1

)

Co

llag

en (n

= 1

)

Dim

eth

ylp

oly

silo

xan

e (s

ilico

ne)

(n =

3)

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er

lip, n

aso

gen

ian

ar

ea, f

acia

l are

a,

chee

ks, c

hin

, an

d

bu

ccal

mu

cosa

Dis

cret

e tr

abec

ula

tio

n o

f th

e m

and

ibu

lar a

nd

su

bm

and

ibu

lar

sub

cuta

neo

us

fat

rela

ted

to

infla

mm

atio

n c

han

ges

; in

ten

se

infla

mm

ato

ry p

roce

sses

aff

ecti

ng

al

mo

st t

he

enti

re s

ub

cuta

neo

us

cellu

lar t

issu

e co

veri

ng

th

e m

axill

ae a

nd

th

e flo

or o

f th

e m

ou

th a

nd

a la

rge

par

t o

f th

e b

ucc

al m

uco

sa; g

ener

aliz

ed,

bila

tera

l, fa

cial

Tu

mef

acti

on

; sw

ellin

g o

f th

e lip

s an

d c

hee

ks

J Am AcAd dermAtol


Req

uen

a et

al.,

200

1 PM

ID:

1139

1099

Sp

ain

/52-

yr-o

ld m

an,

42-y

r-o

ld w

om

an,

two

38-

yr-o

ld

wo

men

4 6–

14 m

o

Art

eco

ll (n

= 1

)

Der

mal

ive

(n =

1)

Silic

on

e (n

= 2

)

Art

eco

ll: N

aso

lab

ial

and

fore

hea

d fo

lds

Der

mal

ive:

Fo

reh

ead

an

d p

erio

cula

r ri

dg

es

Silic

on

e: N

LFs,

chee

ks

Art

eco

ll: E

ryth

emat

ou

s, ri

bb

ed,

pal

pab

le in

du

rati

on

s o

f bo

th

nas

ola

bia

l an

d fo

reh

ead

fold

s

Der

mal

ive:

Ery

them

ato

us

pal

pab

le

ind

ura

tio

ns

on

fore

hea

d

Silic

on

e: E

ryth

emat

ou

s p

alp

able

in

du

rati

on

s o

f bo

th n

aso

lab

ial

fold

s, p

alp

able

ind

ura

tio

ns

on

b

oth

ch

eeks

wit

h m

ild e

ryth

ema

Rey

tan

et

al.,

2007

PM

ID:

1790

3163

G

erm

any/

26-y

r-o

ld m

an

wit

h m

and

ibu

lar

pro

gn

ath

ia

1 9

wk

Evo

len

ce, 2

.9 m

l ove

r tw

o s

essi

on

s Ph

iltru

m a

rea,

ve

rmill

ion

bo

rder

, an

d li

p re

d

No

t re

po

rted

N

ot

rep

ort

ed

Rey

tan

et

al.,

2008

PM

ID:

1911

2805

G

erm

any/

61-y

r-o

ld C

auca

sian

H

IV- p

osi

tive

man

p

rese

nte

d w

ith

faci

al

lipo

atro

ph

y; p

atie

nt

also

has

his

tory

of

hep

atit

is C

1 14

mo

Ev

ole

nce

, 5 m

l in

p

erio

cula

r reg

ion

an

d 6

ml i

n c

hee

k au

gm

enta

tio

n; t

ota

l ov

er fo

ur t

reat

men

ts

Ch

eek,

per

iocu

lar

reg

ion

N

ot

rep

ort

ed

No

ne

rep

ort

ed; c

osm

etic

resu

lts

per

sist

ed fo

r 14

mo.

Ric

ci e

t al

., 20

07 P

MID

: 18

3208

35

Ital

y/M

en b

etw

een

43

and

78

yr o

ld w

ith

se

vere

dys

ph

agia

ca

use

d b

y p

arti

al

lary

ng

ecto

my

7 1

yr

Zyp

last

(bov

ine

colla

gen

) La

ryn

go

pla

sty

No

t re

po

rted

Fo

r tw

o p

atie

nts

(28.

5%, c

ases

5

and

6),

on

ly a

par

tial

po

siti

ve

resu

lt w

as a

chie

ved,

as

1 m

o

afte

r an

init

ial i

mp

rove

men

t, d

ysp

hag

ia fo

r liq

uid

s w

as a

gai

n

ob

serv

ed; t

hes

e tw

o p

atie

nts

h

ad v

ery

diffi

cult

an

ato

mic

al

situ

atio

ns,

wit

h a

wid

e n

eog

lott

ic

insu

ffici

ency

.

In o

ne

pat

ien

t (1

4.4%

, cas

e 7)

, p

osi

tive

resu

lts

wer

e n

ot

ach

ieve

d d

esp

ite

colla

gen

in

ject

ion

th

rou

gh

fib

er

end

osc

op

y, a

nd

follo

wed

b

y PD

MS

inje

ctio

n t

hro

ug

h

mic

rola

ryn

go

sco

py.

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D; A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

PM

ID, P

ub

Med

iden

tific

atio

n n

um

ber

; USA

, Un

ited

Sta

tes;

NLF

, nas

ola

bia

l fo

ld; H

A, h

yalu

ron

ic a

cid

; WA

S, W

rin

kle

Ass

essm

ent

Scal

e; A

Es, a

dve

rse

even

ts; P

MM

A, p

oly

met

hyl

met

hac

ryla

te; R

CT,

ran

do

miz

ed c

on

tro

lled

tri

al; F

FAS,

Fac

ial F

old

Ass

essm

ent

Scal

e; W

SRS,

Wri

nkl

e Se

veri

ty R

atin

g S

cale

; GA

IS, G

lob

al A

esth

etic

Im

pro

vem

ent

Scal

e; M

FWS,

Mo

difi

ed F

itzp

atri

ck W

rin

kle

Scal

e; C

aHA

, cal

ciu

m h

ydro

xyla

pat

ite;

HC

, hu

man

-bas

ed c

olla

gen

; LRS

, Lem

per

le R

atin

g S

cale

; CFB

G, c

lass

ic fo

reig

n b

od

y ty

pe

gra

nu

lom

a; C

MB,

cys

tic

and

mac

rop

hag

ic-t

ype

gra

nu

lom

as; H

IV, h

um

an im

mu

no

defi

cien

cy v

iru

s; P

DM

S, p

oly

dim

eth

ylsi

loxa

ne.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

CaH

A F

iller

s R

and

om

ized

Co

ntr

olle

d T

rial

: No

. of

Stu

die

s, 3

Mo

ers-

Car

pi e

t al

., 20

07 P

MID

: 18

0860

52

Euro

pe/

Enro

lled

p

atie

nts

had

m

od

erat

e o

r sev

ere

NLF

s

205

(192

) 4,

8, 1

2 m

o

Rad

iess

e (C

aHA

), 2.

21 m

l to

tal v

olu

me

(n =

70)

Juvé

der

m 2

4 (H

A-1

A),

4.78

ml t

ota

l vo

lum

e (n

= 3

3)

Juvé

der

m 2

4HV

(HA

-1B

), 2.

94 m

l to

tal v

olu

me

Perl

ane

(HA

-2),

2.89

ml

tota

l vo

lum

e (n

= 6

5)

Pati

ents

tre

ated

wit

h e

ith

er C

aHA

g

el o

r HA

for t

he

corr

ecti

on

of

bo

th N

LFs.

Nea

rly

all p

atie

nts

(n

= 1

89) r

ecei

ved

a to

uch

-up

tr

eatm

ent

at 4

mo.

1. P

atie

nt

sati

sfac

tio

n

2. In

vest

igat

or G

AIS

an

alys

is

3. W

RSR

anal

ysis

No

ser

iou

s A

Es re

qu

irin

g in

terv

enti

on

w

ere

rep

ort

ed a

t an

y ti

me

po

ints

fo

r an

y o

f th

e in

ject

ed m

ater

ials

.

Mo

ers-

Car

pi e

t al

., 20

08 P

MID

: 18

0931

99

Ger

man

y an

d S

pai

n/

Mo

der

ate

to s

ever

e N

LFs

(3 o

r 4 o

n

WSR

S)

60 (5

8)

6, 9

, 12

mo

R

adie

sse

Res

tyla

ne

Volu

me

req

uir

ed fo

r co

rrec

tio

n in

CaH

A-

trea

ted

fold

was

30%

le

ss t

han

th

e vo

lum

e o

f NA

SHA

.

Pati

ents

rece

ived

tw

o in

ject

ion

s 3

mo

ap

art.

At

the

init

ial v

isit

, p

atie

nt

was

tre

ated

wit

h C

aHA

to

co

rrec

t o

ne

NLF

an

d N

ASH

A

to c

orr

ect

the

oth

er N

LF. A

t th

e 3-

mo

vis

it, p

atie

nts

rece

ived

a

tou

ch-u

p t

reat

men

t in

bo

th

fold

s.

1. G

AIS

rati

ng

s

2. B

lind

ed e

valu

ato

rs

rati

ng

Bo

th p

rod

uct

s w

ere

safe

an

d w

ell

tole

rate

d. N

o s

erio

us

AEs

wer

e re

po

rted

wit

h e

ith

er t

reat

men

t.

Fou

r AEs

wer

e re

po

rted

: tw

o

hem

ato

mas

, on

e n

od

ule

, an

d

on

e ex

tru

sio

n (o

f 118

fold

s in

ject

ed t

wo

tim

es e

ach

du

rin

g

the

cou

rse

of t

he

stu

dy)

. Th

e tw

o

hem

ato

mas

reso

lved

in 4

–5 d

ays

wit

h n

o fu

rth

er c

om

plic

atio

ns.

The

no

du

le w

as t

reat

ed w

ith

0.2

ml o

f tr

iam

cin

olo

ne

acet

on

ide

and

was

cl

eare

d in

14

day

s. Th

e ex

tru

sio

n

app

eare

d in

a N

ASH

A-t

reat

ed fo

ld.

It w

as t

reat

ed w

ith

an

tib

ioti

cs a

nd

re

solv

ed w

ith

ou

t co

mp

licat

ion

s. Sm

ith

et

al.,

2007

PM

ID:

1808

6048

USA

/Po

ten

tial

su

bje

cts

wer

e re

qu

ired

to

hav

e sy

mm

etri

c,

mo

der

ate

to d

eep

N

LFs

117

(113

) 1,

3, 6

mo

R

adie

sse

(Co

llag

en)

Co

smo

pla

st (C

aHA

)

Each

sid

e w

as t

reat

ed u

nti

l, in

th

e ju

dg

men

t o

f th

e in

vest

igat

or,

an o

pti

mal

resu

lt w

as a

chie

ved

. A

t 2

wk

afte

r tre

atm

ent,

sub

ject

s co

uld

rece

ive

tou

ch-

up

inje

ctio

ns

at t

he

dis

cret

ion

o

f th

e p

hys

icia

n (o

ccu

rred

at

2-w

k in

terv

als;

max

imu

m o

f tw

o

add

itio

nal

tre

atm

ent

sess

ion

s).

Qu

alify

ing

su

bje

cts

rece

ived

CaH

A

pro

du

ct o

n o

ne

sid

e, a

nd

th

e H

C

pro

du

ct o

n t

he

oth

er.

1. N

um

ber

of i

nje

ctio

n

sess

ion

s re

qu

ired

: b

asel

ine

on

ly

2. M

ean

ch

ang

e in

LRS

fro

m b

asel

ine,

at

6 m

o

3. S

ub

ject

-by-

sub

ject

d

irec

t co

mp

aris

on

, at

6 m

o

4. G

AIS

sco

re o

f Im

pro

ved,

Mu

ch

Imp

rove

d, o

r Ver

y M

uch

Imp

rove

d

5. In

vest

igat

or a

nd

su

bje

ct p

refe

ren

ce

Safe

ty a

nal

ysis

incl

ud

ed a

ll 11

7 su

bje

cts.

Co

nsi

sten

t w

ith

oth

er in

ject

able

fille

r cl

inic

al s

tud

ies,

eryt

hem

a, e

dem

a,

and

ecc

hym

ose

s w

ere

som

e o

f th

e m

ost

co

mm

on

pro

du

ct-r

elat

ed

AEs

. Bo

th e

dem

a an

d b

ruis

ing

wer

e si

gn

ifica

ntl

y m

ore

co

mm

on

on

C

aHA

- tre

ated

sid

es t

han

th

e H

C

sid

e (p

< 0

.001

). Th

ese

reac

tio

ns

last

ed a

pp

roxi

mat

ely

1 w

k af

ter

any

inje

ctio

n. M

ean

du

rati

on

for

eryt

hem

a w

as 2

–3 w

k, w

ith

no

si

gn

ifica

nt

diff

eren

ce b

etw

een

th

e tw

o t

reat

men

ts.

CaH

A: o

ne

no

du

le; H

C: t

hre

e n

od

ule

s. N

o g

ran

ulo

mas

, alle

rgie

s, u

lcer

atio

ns

or o

ther

ser

iou

s A

Es w

ere

not

ed.

J Am AcAd dermAtol


Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f st

ud

ies,

15

Bec

ker,

2008

PM

ID:

1852

0907

USA

/Gen

eral

p

op

ula

tio

n

24 (1

8)

2–48

mo

R

adie

sse,

0.2

5–1.

3 m

l at

init

ial i

nje

ctio

n

Vari

ou

s lo

cati

on

s, n

um

ber

s o

f in

ject

ion

s

1. P

atie

nt

sati

sfac

tio

n

(0–

10)

No

t re

po

rted

Bee

r et

al.,

2008

PM

ID:

1845

9517

USA

/Wo

men

wit

h

sig

ns

of m

idfa

ce

volu

me

loss

19 (1

6)

1, 3

, 6 m

o

Rad

iess

e, v

olu

me

at d

iscr

etio

n o

f ph

ysic

ian

C

hee

k

Tou

ch-u

p t

reat

men

ts

wer

e ad

min

iste

red

at

1 m

o a

t d

iscr

etio

n

of p

hys

icia

n.

1. P

hys

icia

n-e

valu

ated

ae

sth

etic

rati

ng

s

2. P

atie

nt

sati

sfac

tio

n

3. P

hys

icia

n G

AIS

rati

ng

s

Rep

ort

ed in

tw

o p

atie

nts

(13%

). O

ne

rep

ort

ed m

ild e

dem

a an

d

hem

ato

ma,

reso

lvin

g in

less

th

an 2

wk.

Th

e re

po

rted

mild

ec

chym

osi

s an

d e

dem

a af

ter

init

ial t

reat

men

t, an

d m

ild e

dem

a af

ter t

ou

ch-u

p t

reat

men

t. Th

ese

reso

lved

wit

hin

5 d

ays.

Ber

lin e

t al

., 20

08 P

MID

: 18

5471

84

USA

/Su

bje

cts

wit

h

pro

min

ent

nas

ola

bia

l rh

ytid

es 5

6 m

o

Rad

iess

e, 0

.1–0

.2 m

l R

igh

t p

ost

auri

cula

r are

a 1.

Po

stau

ricu

lar b

iop

sies

u

sin

g t

rad

itio

nal

h

emat

oxyl

in a

nd

eo

sin

st

ain

ing

2. P

SR s

tain

ing

3. IH

C a

nal

ysis

All

five

sub

ject

s co

mp

lete

d t

he

stu

dy

wit

ho

ut

any

seri

ou

s o

r lo

ng

-ter

m c

om

plic

atio

ns.

Car

ruth

ers

et

al.,

2008

PM

ID:

1854

7186

USA

/Pat

ien

ts w

ith

lip

oat

rop

hy

or

pro

no

un

ced

NLF

s

58

No

ne

Rad

iess

e N

ot

rep

ort

ed

1. X

-ray

sca

n

2. C

T sc

an

3. O

ther

No

t re

po

rted

Jaco

vella

et

al.,

2006

PM

ID:

1693

6540

Arg

enti

na/

Faci

al

inje

ctio

ns

for

cosm

etic

pu

rpo

ses

40 (4

0)

18 m

o

Rad

iess

e, 0

.5–2

.0 m

l (a

vera

ge,

0.7

5 m

l) In

ject

ion

s to

th

e g

lab

ella

r wri

nkl

es,

nas

ola

bia

l fo

lds,

lips,

no

se, a

nd

/or

infr

aorb

ital

are

a

1. P

atie

nt

sati

sfac

tio

n

No

sys

tem

ic e

ffec

ts o

r im

mu

no

log

ic

resp

on

ses

Ecch

ymo

sis

and

hem

ato

ma

in t

wo

p

atie

nts

Jan

sen

et

al.,

2006

PM

ID:

1693

6541

USA

/Fac

ial i

nje

ctio

ns

for c

osm

etic

p

urp

ose

s

609

(155

, 6

mo

) (1

12,

12–

24

mo

)

6, 1

2–24

m

o

Rad

iess

e

Nas

ola

bia

l fo

lds

0.62

ml e

ach

(n =

395

are

as)

Up

per

lip

, 0.6

ml;

low

er li

p, 0

.25

ml (

n =

338

are

as,

com

bin

ed li

ps)

Rad

ial l

ip li

ne,

0.2

5 m

l per

lin

e (n

= 1

63 a

reas

)

Co

rner

of m

ou

th, 0

.28

ml (

n =

125

are

as)

Mar

ion

ette

lin

es, 0

.49

ml e

ach

sid

e (n

= 7

5 ar

eas)

Gla

bel

lar l

ines

, 0.2

2 m

l (n

= 1

06 a

reas

)

Ch

in/c

hee

k lin

es, 0

.20

ml (

n =

50

area

s)

Acn

e sc

ars,

0.12

ml (

n =

33

area

s)

Scar

def

orm

itie

s, 0.

2–0.

4 m

l (n

= 2

1 ar

eas)

Faci

al d

epre

ssio

n (H

IV li

po

atro

ph

y), 5

.25

ml

(n =

14

area

s)

Ch

eek

aug

men

tati

on

, 0.8

5 m

l eac

h s

ide

(n

= 1

4 ar

eas)

Nas

al d

epre

ssio

ns,

0.2

ml (

n =

6 a

reas

)

Tear

tro

ug

hs,

0.35

ml (

n =

8 a

reas

)

Tou

ch-u

ps,

aver

age

0.3

ml

Inje

ctio

ns

to t

he

nas

ola

bia

l fo

lds,

mar

ion

ette

lin

es, o

ral

com

mis

sure

, ch

eeks

, ch

in, l

ips,

and

/or

rad

ial l

ip li

nes

1. T

reat

men

t sa

tisf

acti

on

su

rvey

(sca

le o

f 1–5

) an

d c

on

tin

ued

use

2. A

Es

Dev

elo

pm

ent

of e

asily

tre

ated

n

od

ule

s in

48

pat

ien

ts (4

2 fo

r lip

m

uco

sa a

ug

men

tati

on

an

d s

ix

for r

adia

l lip

lin

es)



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/

po

pu

lati

on

typ

e Sa

mp

le

size

Fo

llo

w-

up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Mar

mu

r et

al.,

2009

PM

ID:

1970

8875

USA

/Fem

ale

pat

ien

ts

aged

60–

80 y

r w

ith

so

ft- t

issu

e d

efici

ency

of t

he

do

rsa

of t

he

han

ds

5 24

wk

Rad

iess

e, 1

.3 m

l per

han

d fo

r fo

ur p

atie

nts

an

d 2

.6

ml p

er h

and

for o

ne

pat

ien

t D

ors

al s

ide

of h

and

Pa

tien

t sa

tisf

acti

on

leve

ls

All

pat

ien

ts h

ad m

ild to

mo

der

ate

eryt

hem

a an

d e

dem

a th

at d

id

no

t re

qu

ire

trea

tmen

t an

d

sub

sid

ed w

ith

in 3

–6 d

ays.

On

e p

atie

nt

had

ed

ema

reo

ccu

r 10

day

s af

ter t

reat

men

t an

d

con

tin

ue

for 3

wk.

On

e p

atie

nt

ob

serv

ed e

cch

ymo

sis

last

ing

7 d

ays

fro

m t

reat

men

t an

d g

rad

ual

ly re

solv

ing

wit

ho

ut

inte

rven

tio

n.

An

oth

er p

atie

nt

rep

ort

ed a

feel

ing

o

f war

mth

an

d p

ruri

tus

last

ing

fo

r 24

hr t

hat

cle

ared

wit

hin

2

day

s.

Mar

mu

r et

al.,

2009

PM

ID:

1970

8876

USA

/Pat

ien

ts a

ged

18

yr a

nd

old

er

wit

h F

itzp

atri

ck

skin

typ

es IV

–VI

100

6 m

o

Rad

iess

e, 0

.6–2

.8 m

l Fa

cial

wri

nkl

es a

nd

fo

lds,

incl

ud

ing

NLF

s In

cid

ence

of h

yper

tro

ph

ic

scar

rin

g, k

elo

id

form

atio

n, a

nd

h

yper

pig

men

tati

on

or

hyp

op

igm

enta

tio

n

No

ne

rep

ort

ed

O’H

ara

et a

l.,

2006

PM

ID:

1665

1970

USA

/Pat

ien

ts

un

der

go

ing

zy

go

mat

ic

aug

men

tati

on

8 (8

) 1,

7 d

ays;

3,

6, 1

2 m

o

Hyd

roxy

apat

ite

inje

ctio

ns

in 0

.5- t

o 1

.0-c

c in

crem

ents

fro

m 2

.0–4

.0 c

c p

er s

ide

(a

vera

ge,

2.5

cc)

Tran

sco

nju

nct

ival

in

ject

ion

s in

to t

he

sub

per

iost

eal m

alar

p

ock

ets

1. P

atie

nt

sati

sfac

tio

n

2. P

reo

per

ativ

e,

po

sto

per

ativ

e, a

nd

fo

llow

-up

rig

ht

ang

le

dis

tan

ce fr

om

th

e p

oin

t o

f mal

ar p

rom

inen

ce to

th

e n

asal

e- s

ub

nas

ale

line

was

sig

nifi

can

tly

less

in a

ll p

ost

op

erat

ive

and

follo

w-u

p

mea

sure

men

ts

com

par

ed w

ith

th

e sa

me

pat

ien

t’s

pre

op

erat

ive

mea

sure

men

ts .

No

ne

rep

ort

ed

J Am AcAd dermAtol


Roy

et

al.,

2006

PM

ID:

1697

0693

USA

/Pat

ien

ts

req

ues

tin

g

faci

al s

oft

- tis

sue

aug

men

tati

on

, th

ree

men

an

d 7

9 w

om

en

82

3–6

mo

R

adie

sse

The

mea

n a

mo

un

t o

f m

ater

ial i

nje

cted

at

th

e in

itia

l vis

it

was

0.2

9 m

l in

th

e m

elo

lab

ial f

old

(per

si

de)

, 0.3

4 m

l in

th

e u

pp

er li

p, 0

.37

ml i

n t

he

low

er li

p,

and

0.1

2 m

l in

th

e in

frac

om

mis

sure

fold

The

mea

n a

mo

un

t o

f m

ater

ial i

nje

cted

d

uri

ng

tou

ch-u

p

inje

ctio

ns

was

0.1

5 m

l in

th

e m

elo

lab

ial

fold

s (p

er s

ide)

, 0.1

3 m

l in

th

e u

pp

er li

p,

and

0.1

2 m

l in

th

e lo

wer

lip

Pati

ents

an

d

surg

eon

seva

luat

ed

the

loo

k an

d fe

elo

f th

e im

pla

nt

bas

ed o

n

thef

ollo

win

g s

cale

:

1 =

un

sati

sfac

tory

2 =

po

or

3 =

sat

isfa

cto

ry

4 =

ver

y g

oo

d

5 =

exc

elle

nt.

Mild

ery

them

a an

d m

inim

al e

dem

a la

stin

g fo

r sev

eral

ho

urs

was

th

e m

ost

co

mm

on

sid

e ef

fect

.

Six

(7%

) dev

elo

ped

su

bm

uco

sal

no

du

les

in t

he

lips.

Sad

ick

et a

l.,

2007

PM

ID:

1808

6049

USA

/Su

bje

cts

wit

h

faci

al s

oft

-tis

sue

defi

cien

cy

amen

able

to

trea

tmen

t

113

6 m

o

Rad

iess

e, 1

.0 m

l (n

= 1

02),

2.0

ml (

n =

12)

M

ost

co

mm

on

ly t

reat

ed

site

was

th

e N

LF

(n =

86)

. Oth

er s

ites

in

clu

ded

per

iora

l lin

es, a

cne

scar

s, te

ar

tro

ug

h d

epre

ssio

ns,

and

pre

jow

l su

lcu

s.

75 (6

7%) h

ad a

sin

gle

in

ject

ion

ses

sio

n; 3

8 (3

4%) h

ad m

ult

iple

se

ssio

ns.

1. E

ffica

cy ra

tin

g b

y tr

eati

ng

ph

ysic

ian

(1–5

), 6

mo

2. E

ffica

cy ra

tin

g b

y p

atie

nt

No

alle

rgic

reac

tio

ns

wer

e re

po

rted

.

Mild

ery

them

a an

d m

inim

al e

dem

a (f

ew h

ou

rs to

a fe

w d

ays)

wer

e th

e m

ost

co

mm

on

sid

e ef

fect

s.

Seve

n p

atie

nts

rep

ort

ed m

ino

r A

Es. A

ll w

ere

con

sid

ered

sh

ort

-te

rm a

nd

reso

lved

wit

hin

1 m

o.

Tran

sien

t ec

chym

osi

s

(n =

3),

sub

mu

cosa

l no

du

les

of

the

lip (n

= 2

), in

flam

mat

ion

an

d

edem

a (n

= 2

) res

olv

ed w

ith

ora

l p

red

nis

olo

ne.

Silv

ers

et a

l.,

2006

PM

ID:

1693

6543

USA

/Pat

ien

ts w

ith

fa

cial

lip

oat

rop

hy

seco

nd

ary

to H

IV

100

(100

) 3,

6, 1

2, 1

8 m

o

Rad

iess

e, 4

.8 m

l (av

erag

e)

Inje

ctio

ns

to t

he

chee

k ar

ea (s

ub

mal

ar)

per

form

ed b

y th

e in

vest

igat

ors

Init

ial i

nje

ctio

ns

follo

wed

up

w

ith

su

bse

qu

ent

inje

ctio

ns

at 1

, 6, a

nd

18

mo

1. G

AIS

imp

rove

men

t at

3

mo

an

d c

on

firm

atio

n

usi

ng

ph

oto

gra

ph

y

2. G

AIS

imp

rove

men

t at

6

mo

an

d s

kin

fold

th

ickn

ess

at 3

an

d 6

mo

3. G

AIS

imp

rove

men

t at

12

mo

4. G

AIS

imp

rove

men

t at

18

mo

AEs

at

12 m

o w

ere

mild

, no

t u

nex

pec

ted,

an

d s

ho

rt in

d

ura

tio

n.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/

po

pu

lati

on

typ

e Sa

mp

le

size

Fo

llo

w-

up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Skla

r et

al.,

2004

PM

ID:

1509

9322

USA

/Pat

ien

ts w

ith

su

bcu

tan

eou

s o

r dee

p t

issu

e at

rop

hy

64 (6

4)

6 m

o

Rad

ian

ce F

N

Nas

ola

bia

l fo

lds,

0.91

ml (

aver

age)

; ran

ge,

0.4

–2.0

m

l (n

= 5

2)

Tear

tro

ug

h, 0

.35

ml (

aver

age)

; ran

ge,

0.3

–0.7

ml

(n =

15)

Lip

s 0.

67 m

l (av

erag

e); r

ang

e, 0

.2–1

.4 m

l (n

= 1

5)

Intr

aora

l, 0.

29 m

l (av

erag

e); r

ang

e, 0

.1–0

.5 m

l (n

= 1

1)

Ch

eeks

, 0.6

0 m

l (av

erag

e); r

ang

e, 0

.3–1

.2 m

l (n

= 4

)

Men

tal c

reas

e, 0

.15

ml (

aver

age)

; ran

ge,

0.1

–0.2

ml

(n =

2)

Ab

ove

up

per

lip

, 0.2

0 m

l (av

erag

e); r

ang

e, 0

.2 m

l (n

= 1

)

Bu

ccal

reg

ion

, 2.0

ml (

aver

age)

; ran

ge,

2.9

ml (

n =

1)

Inje

ctio

ns

in a

re

tro

gra

de

tech

niq

ue

to N

LFs,

tear

tro

ug

h, l

ips,

intr

aora

l, ch

eeks

, m

enta

l cre

ase,

ab

ove

up

per

lip

, bu

ccal

re

gio

n

Pati

ent

and

ph

ysic

ian

sa

tisf

acti

on

Th

ree

pat

ien

ts h

ad p

alp

able

bu

mp

s.

On

e p

atie

nt

had

ove

rco

rrec

tio

n o

f th

e te

ar t

rou

gh

are

a re

sult

ing

in

pu

ffy

eyes

.

Stu

pak

et

al.,

2007

PM

ID:

1737

2068

USA

/Pat

ien

ts w

ith

p

ost

rhin

op

last

y co

nto

ur

irre

gu

lari

ties

or

asym

met

ry

13

2.5

mo

R

adie

sse;

mea

n d

ose

, 0.1

9 m

l D

ors

um

an

d b

ilate

ral

wal

ls o

f th

e n

asal

re

gio

n

Pati

ent

sati

sfac

tio

n

Pho

tog

rap

hic

im

pro

vem

ent

No

ser

iou

s co

mp

licat

ion

s o

ccu

rred

in

an

y p

atie

nts

.

On

e p

atie

nt

des

crib

ed a

per

iod

of

seve

ral d

ays

of m

ild e

ryth

ema,

b

ut

reso

lved

wit

ho

ut

trea

tmen

t.

Tzik

as, 2

004

PMID

: 15

2627

17

USA

/Pat

ien

ts s

eeki

ng

so

ft-t

issu

e au

gm

enta

tio

n

90

6 m

o

Rad

ian

ce F

N, 0

.2 m

l (av

erag

e)

Inje

ctio

n s

ub

der

mal

ly

bet

wee

n d

erm

is a

nd

su

bcu

tan

eou

s fa

t to

th

e N

LFs,

gla

bel

lar

rhyt

ides

, mar

ion

ette

lin

es, p

rejo

wl

dep

ress

ion

s, ac

ne

scar

s, an

d s

urg

ical

so

ft-t

issu

e d

efec

ts

Inje

ctio

n to

th

e lip

s in

th

e p

lan

e su

per

ficia

l to

th

e o

rbic

ula

ris

mu

scle

Ap

pea

ran

ce, s

oft

nes

s, ov

eral

l pat

ien

t sa

tisf

acti

on

Seve

n p

atie

nts

had

per

sist

ent

visi

ble

m

uco

sal l

ip n

od

ule

s.

Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

2

Ro

khsa

r et

al.,

2008

PM

ID:

1838

4613

U

SA/S

ub

ject

s w

ith

or w

ith

ou

t a

his

tory

of s

urg

ical

rh

ino

pla

sty

14

6 m

o

Rad

iess

e, m

ean

0.

27 m

l at

init

ial v

isit

No

nsu

rgic

al n

asal

reco

nto

uri

ng,

30

% o

f pat

ien

ts re

qu

este

d

add

itio

nal

tou

ch-u

ps

at 2

-wk

follo

w-u

p v

isit

1. P

atie

nt

sati

sfac

tio

n

57%

sh

ow

ed e

cch

ymo

ses

for 2

–7 d

ays.

64%

had

ed

ema

for 2

–5 d

ays.

No

infe

ctio

n o

r su

rfac

e ir

reg

ula

rity

AEs

w

ere

reco

rded

at

eith

er v

isit

.

Tzik

as, 2

008

PMID

: 185

4718

8 U

SA/P

atie

nts

>18

yr w

ith

a

faci

al s

oft

- tis

sue

defi

cien

cy

amen

able

to t

reat

men

t

1000

1

yr

Rad

iess

e; m

ean

vo

lum

e, 1

.9 m

l Va

riet

y fa

cial

co

nto

uri

ng

ap

plic

atio

ns,

maj

ori

ty N

LFs

and

mar

ion

ette

lin

es

1. D

ura

tio

n o

f ef

fect

M

ino

r; m

ost

reso

lved

wit

ho

ut

trea

tmen

t.

J Am AcAd dermAtol


Cro

ss-S

ecti

on

al S

tud

y: N

o. o

f S

tud

ies,

1

Ala

m e

t al

., 20

07

PMID

: 172

2437

1 U

SA/P

atie

nts

pre

sen

ted

for

corr

ecti

on

of d

epre

ssio

ns

of t

he

NLF

s

22 (1

8)

1–1.

5 yr

R

adie

sse,

1–2

m

l in

eac

h

NLF

NLF

s 1.

Lo

ng

evit

y o

f res

ult

s

2. P

atie

nt

sati

sfac

tio

n w

ith

C

aHA

Of t

he

18 p

atie

nts

, all

rep

ort

ed a

t le

ast

mild

po

stin

ject

ion

red

nes

s an

d s

wel

ling,

wh

ich

ab

ated

wit

hin

1–

5 d

ays.

Bru

isin

g w

as re

po

rted

by

few

er t

han

hal

f an

d re

solv

ed w

ith

in

4–10

day

s. Pa

lpab

le b

ut

no

t vi

sib

le

no

du

les

wer

e re

po

rted

by

two

of 1

8 p

atie

nts

; th

ese

reso

lved

wit

hin

3 m

o

of i

nje

ctio

n.

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

11

Bee

r, 20

07 P

MID

: 17

7636

19

USA

/59-

yr-o

ld w

om

an

1 6

wk

Rad

iess

e, 3

.9 m

l N

aso

lab

ial c

reas

es a

nd

mar

ion

ette

lin

es

No

t re

po

rted

2

wk

afte

r tre

atm

ent,

exam

inat

ion

reve

aled

an

o

paq

ue,

wh

ite

no

du

le, 1

.5 c

m,

loca

ted

on

th

e la

bia

mu

cosa

o

f th

e lo

wer

lip

; no

du

le w

as

solid

an

d n

on

mal

leab

le.

Pati

ent

was

tre

ated

wit

h K

enal

og

(t

hre

e tr

eatm

ents

of 2

0 m

g/

ml,

2 w

k ap

art)

, wh

ich

red

uce

d

the

size

of t

he

no

du

le to

1 c

m.

Feen

ey e

t al

., 20

09 P

MID

: 19

6644

80

USA

/Pat

ien

ts w

ith

h

yper

atte

nu

atin

g

hyp

erm

etab

olic

su

bcu

tan

eou

s le

sio

ns

and

a h

isto

ry o

f fac

ial

inje

ctio

ns

5 (5

) N

A

Rad

iess

e 1.

Inje

ctio

ns

to t

he

left

in

fraz

ygo

mat

ic re

gio

n

2. In

ject

ion

s to

th

e in

frao

rbit

al a

nd

in

fraz

ygo

mat

ic re

gio

ns

3. In

ject

ion

s to

th

e in

frao

rbit

al a

nd

in

fraz

ygo

mat

ic re

gio

ns

4. In

ject

ion

s to

th

e in

frao

rbit

al,

nas

ola

bia

l, p

aro

tid

an

d p

erio

ral

reg

ion

s

5. In

ject

ion

s to

th

e in

frao

rbit

al,

infr

azyg

om

atic

, an

d p

erio

ral

reg

ion

s

No

t re

po

rted

A

ll ca

ses

had

su

bcu

tan

eou

s h

igh

- att

enu

atio

n m

ater

ial o

n

CT

scan

(ran

ge,

280

–700

HU

), w

hic

h w

as F

DG

avi

d o

n P

ET,

wit

h a

SU

V ra

ng

e o

f 2.9

–13.

4.

MRI

dem

on

stra

ted

a

het

ero

gen

eou

s in

term

edia

te

sig

nal

inte

nsi

ty s

ub

cuta

neo

us

lesi

on

wit

h e

nh

ance

men

t p

ost

-gad

olin

ium

in o

ne

case

.

Go

din

et

al.,

2006

PM

ID:

1654

9735

USA

/Pat

ien

ts

un

der

go

ing

faci

al

aug

men

tati

on

101

(61)

10

mo

R

adie

sse

(n =

72)

Rad

iess

e an

d

Res

tyla

ne

(n

= 2

9)

Inje

ctio

n to

th

e N

LFs,

up

per

an

d

low

er li

p v

erm

illio

n b

ord

ers,

“lip

stic

k lin

es” a

nd

per

iora

l lin

es

Imm

edia

te a

nd

lo

ng

-ter

m p

atie

nt

sati

sfac

tio

n s

urv

ey

(10-

po

int

scal

e)

No

t re

po

rted



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Kan

chw

ala

et a

l.,

2005

PM

ID:

1598

5788

USA

/Pat

ien

ts

un

der

go

ing

faci

al

aug

men

tati

on

976

3, 6

, 9, 1

2 m

o

Au

tolo

go

us

fat

(n =

697

)

Hyl

afo

rm

(n =

52)

Res

tyla

ne

(n =

86)

Rad

iess

e (n

= 1

41)

Nas

ola

bia

l fo

lds,

lips,

gla

bel

la

1. T

ype

of p

rod

uct

u

sed

2. A

nat

om

ical

reg

ion

in

ject

ed

3. In

fect

ion

rate

4. T

ou

ch-u

p/r

evis

ion

ra

te a

nd

ove

rall

lon

gev

ity

No

t re

po

rted

Ko

tlu

s et

al.,

20

07 P

MID

: 17

6671

06

USA

/66-

yr-o

ld m

an

pre

sen

ted

wit

h

ano

ph

thal

mic

en

op

hth

alm

os

cau

sed

by

an a

ccid

ent 1

6 m

o

Rad

iess

e, t

wo

1.3

-m

l tre

atm

ents

3

wk

apar

t

Left

orb

ital

reg

ion

N

ot

rep

ort

ed

No

ne

rep

ort

ed

Lee

et a

l.,

2008

PM

ID:

1880

6674

Ko

rea/

37-y

r-o

ld w

om

an

wit

h 2

-mo

his

tory

of

fulln

ess

and

pto

sis

of

the

left

up

per

eye

lid

1 4

mo

R

adie

sse

Eyel

id a

nd

orb

ital

reg

ion

N

ot

rep

ort

ed

Pati

ent

com

pla

ined

of f

ulln

ess

and

pto

sis

of t

he

left

up

per

ey

elid

for 8

wk

that

dev

elo

ped

ab

rup

tly

and

wo

rsen

ed o

ver

2– 3

wk.

Mar

ked

pto

sis

of t

he

left

up

per

ey

elid

an

d e

leva

tio

n o

f th

e le

ft

low

er e

yelid

wer

e o

bse

rved

.Su

rgic

al e

xcis

ion

was

per

form

ed

and

gra

y-w

hite

mas

ses

and

a

gel-l

ike

mat

eria

l wer

e fo

und

b

etw

een

the

orb

ital s

eptu

m

and

the

orb

icul

aris

ocu

li m

uscl

e.

Mic

rosc

op

ic e

xam

inat

ion

of

the

spec

imen

sh

ow

ed C

aHA

m

icro

sph

eru

les

surr

ou

nd

ed

by

colla

gen

an

d h

isti

ocy

tes.

San

kar e

t al

., 20

07 P

MID

: 17

6708

76

USA

/51-

yr-o

ld w

om

an

pre

sen

ted

wit

h c

hie

f co

mp

lain

t o

f a lu

mp

o

n t

he

mu

cosa

l as

pec

t o

f her

low

er li

p

on

th

e le

ft s

ide

1 U

nkn

ow

n

Rad

iess

e Li

p

No

t re

po

rted

Le

sio

n o

f yel

low

no

du

le

mea

suri

ng

6 ×

3 m

m w

ith

w

ell-

defi

ned

, irr

egu

larl

y sh

aped

bo

rder

s th

at w

as fi

rm

on

pal

pat

ion

; aft

er re

mov

al,

exci

sed

mas

s w

as p

ale

yello

w

and

rub

ber

y in

co

nsi

sten

cy.

Fin

al h

isto

log

ic d

iag

no

sis

was

th

e p

rese

nce

of a

fore

ign

mat

eria

l al

on

g w

ith

a fl

ori

d fo

reig

n

bo

dy

gia

nt

cell

reac

tio

n

of t

he

soft

-tis

sue,

ch

ron

ic

infla

mm

atio

n, a

nd

fib

rosi

s.

J Am AcAd dermAtol


Shu

mak

er e

t al

., 20

09 P

MID

: 19

2073

28

USA

/57-

yr-o

ld w

om

an

pre

sen

ted

wit

h a

se

vera

l-m

on

th h

isto

ry

of e

nla

rgin

g p

laq

ue

of

the

left

su

per

ior N

LF;

afte

r exa

min

atio

n,

pat

ien

t h

ad a

p

earl

y p

laq

ue

that

d

emo

nst

rate

d b

asal

ce

ll ca

rcin

om

a

1 Pr

esen

ted

8 y

r af

ter fi

rst

trea

tmen

t

Rad

iess

e N

aso

lab

ial f

old

N

ot

rep

ort

ed

Fore

ign

bo

dy

gra

nu

lom

a

Sire

s et

al.,

20

08 P

MID

: 18

5208

38

USA

/57-

yr-o

ld

imm

un

oco

mp

eten

t w

om

an w

ho

d

evel

op

ed h

erp

etic

-ap

pea

rin

g s

kin

le

sio

ns

afte

r in

ject

ion

o

f Rad

iess

e in

th

e g

lab

ella

1 6

mo

R

adie

sse,

fou

r 0.3

-m

l tre

atm

ents

G

lab

ella

, mar

ion

ette

lin

es, a

nd

N

LFs

No

t re

po

rted

Pa

tien

t p

rese

nte

d w

ith

te

nd

ern

ess,

tin

glin

g, a

nd

re

dn

ess

wit

h b

um

ps

alo

ng

th

e g

lab

ella

r reg

ion

; exa

min

atio

n

reve

aled

ery

them

a w

ith

ve

sicl

es o

r pu

stu

les,

swel

ling,

an

d te

nd

ern

ess

in t

he

rig

ht

gla

bel

la re

gio

n.

Vag

efi e

t al

., 20

07 P

MID

: 18

0253

56

USA

/Th

ree

wo

men

an

d

on

e m

an; m

ean

ag

e,

36 y

r; al

l wit

h P

EESS

4 45

–71

wk

Rad

iess

e, 1

.3–2

.6

ml

Extr

aco

nal

sp

ace

in t

he

orb

ital

re

gio

n

Eno

ph

thal

mo

s m

easu

red

by

Her

tel

exo

ph

thal

mo

met

ry

On

e p

atie

nt

exp

erie

nce

d

per

ibu

lbar

hem

orr

hag

e re

late

d to

retr

ob

ulb

ar

anes

thes

ia a

dm

inis

trat

ion

d

uri

ng

inje

ctio

n.

Vag

efi e

t al

., 20

08 P

MID

: 18

5208

33

USA

/Pat

ien

ts w

ith

bo

ny

def

ects

of t

he

fro

nta

l b

on

e fr

om

pri

or

trau

ma

or s

urg

ery

3 (t

wo

men

, on

e)

wo

man

) 2–

7 m

o

Rad

iess

e/ca

lciu

m

hyd

roxy

lap

atit

e,

1.3–

3.9

ml

Fille

r in

ject

ed in

to b

on

y d

efec

ts

sub

der

mal

ly, i

n c

on

jun

ctio

n

wit

h o

ther

eye

lid p

roce

du

res

No

t re

po

rted

N

on

e re

po

rted

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D; A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

CaH

A, c

alci

um

hyd

roxy

lap

atit

e; P

MID

, Pu

bM

ed id

enti

ficat

ion

nu

mb

er; N

LF, n

aso

lab

ial f

old

; GA

IS, G

lob

al A

esth

etic

Im

pro

vem

ent

Scal

e; W

SRS,

Wri

nkl

e Se

veri

ty R

atin

g S

cale

; AEs

, ad

vers

e ev

ents

; HA

, hya

luro

nic

aci

d; N

ASH

A, n

on

–an

imal

-sta

bili

zed

hya

luro

nic

aci

d; U

SA, U

nit

ed S

tate

s; H

C, h

um

an-b

ased

co

llag

en; L

RS,

Lem

per

le R

atin

g S

cale

; PSR

, pic

rosi

riu

s re

d ;

IHC

, im

mu

no

his

toch

emis

try;

CT,

co

mp

ute

d to

mo

gra

ph

ic; H

IV, h

um

an im

mu

no

defi

cien

cy v

iru

s; F

DG

, flu

oro

deo

xyg

luco

se; P

ET, p

osi

tro

n e

mis

sio

n to

mo

gra

ph

y; S

UV,

st

and

ard

ized

up

take

val

ue;

MRI

, mag

net

ic re

son

ance

imag

ing

; NA

. no

t ap

plic

able

; PEE

SS, p

ost

enu

clea

tio

n o

r evi

scer

atio

n s

ock

et s

ynd

rom

e.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

PL

LA

Fill

ers

Sys

tem

atic

Rev

iew

: No

. of

Stu

die

s, 1

El-B

eyro

uty

et

al.,

2006

PM

ID:

1691

2248

USA

, En

gla

nd,

an

d

Fran

ce/S

yste

mat

ic

revi

ew o

f stu

die

s co

nd

uct

ed in

H

IV li

po

atro

ph

y p

op

ula

tio

ns

of

wh

ite

men

6 cl

inic

al t

rial

s: V

EGA

, C

hel

sea

and

W

estm

inst

er, L

afau

tie

et a

l., A

PEX

001

, APE

X

002,

an

d B

lue

Paci

fic

Vari

ou

s PL

LA

1. V

EGA

: PLL

A, 4

.0 m

l (n

= 4

7)

2. C

hel

sea

and

Wes

tmin

ster

: PL

LA, 3

.0 m

l (n

= 2

9)

3. L

afau

tie

et a

l.: P

LLA

, 2.5

ml

(n =

94)

4. A

PEX

001

: PLL

A, 1

.0–8

.0 m

l (n

= 1

00)

5. A

PEX

002

: PLL

A, 8

.0 m

l (n

= 9

9)

6. B

lue

Paci

fic G

rou

p: P

LLA

aci

d,

6.0

ml (

n =

99)

Inje

ctio

ns

to t

he

chee

ks fo

r th

e tr

eatm

ent

of

HIV

1. T

ota

l cu

tan

eou

s th

ickn

ess

2. S

kin

th

ickn

ess

3. P

atie

nt’s

p

erce

pti

on

of

imp

rove

men

t u

sin

g

a VA

S

4. P

atie

nt

sati

sfac

tio

n ra

ted

o

n a

sca

le fr

om

1–

10

5. P

atie

nt

sati

sfac

tio

n ra

ted

o

n a

sca

le fr

om

1–

5

6. F

acia

l ski

n

thic

knes

s

No

du

les

dev

elo

ped

in 2

6 o

f 50

pat

ien

ts (

VEG

A).

Hem

ato

ma

dev

elo

ped

in 1

4 o

f 50

pat

ien

ts (

VEG

A).

Nin

e o

f 30

pat

ien

ts re

po

rted

an

in

ject

ion

-sit

e p

apu

le o

r no

du

le

(Ch

else

a an

d W

estm

inst

er).

39 o

f 70

pat

ien

ts d

evel

op

ed n

od

ule

s (A

PEX

001

).

Six

of 9

9 p

atie

nts

dev

elo

ped

su

bcu

tan

eou

s p

apu

les

(APE

X 0

02).

13 p

atie

nts

dev

elo

ped

inje

ctio

n-s

ite

pap

ule

(Blu

e Pa

cific

Gro

up

).

Two

ser

iou

s A

Es: a

nap

hyl

acti

c re

acti

on

an

d p

erip

her

al fa

cial

pal

sy (L

afau

tie

et a

l.).

Ran

do

miz

ed C

on

tro

lled

Tri

al: N

o. o

f S

tud

ies,

2

Moy

le e

t al

., 20

04 P

MID

: 15

0126

46

UK

/Pat

ien

ts w

ith

H

IV-i

nd

uce

d

faci

al li

po

atro

ph

y

30 (3

0)

0, 1

2, 2

4 w

k N

ew-F

ill im

med

iate

tre

atm

ent

(n

= 1

5)

New

-Fill

del

ayed

tre

atm

ent

Inje

ctio

n in

to t

he

dee

p d

erm

is

over

lyin

g t

he

bu

ccal

fat

pad

1. V

AS

(0–1

0, w

ith

low

sc

ore

s in

dic

atin

g

extr

eme

thin

nes

s)

2. H

AD

S (0

–10,

w

ith

low

sco

res

ind

icat

ing

less

d

epre

ssio

n/

anxi

ety)

3. B

lind

ass

essm

ent

of p

ho

tog

rap

hs

No

ne

rep

ort

ed.

Moy

le e

t al

., 20

06 P

MID

: 16

4946

32

USA

/Pat

ien

ts w

ith

H

IV-r

elat

ed fa

cial

lip

oat

rop

hy

30 (2

7)

18 m

o

Scu

lptr

a (P

LLA

) im

med

iate

tr

eatm

ent,

3.0

ml (

n =

15)

Scu

lptr

a (P

LLA

) del

ayed

tre

atm

ent,

3.0

ml (

n =

15)

Thre

e se

ts o

f b

ilate

ral

inje

ctio

ns,

2 w

k ap

art,

to t

he

dee

p

der

mis

ab

ove

the

bu

ccal

fat

pad

1. E

ffica

cy a

nd

p

atie

nt

sati

sfac

tio

n

asse

ssed

by

a VA

S

2. H

AD

S

On

e ca

se o

f in

ject

ion

-sit

e in

du

rati

on

Nin

e ca

ses

of i

nje

ctio

n-s

ite

no

du

les

J Am AcAd dermAtol


Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f S

tud

ies,

4

Bee

r, 20

07 P

MID

: 18

0860

54

USA

/Su

bje

cts

wit

h fa

cial

sc

ars

resu

ltin

g

fro

m m

od

erat

e to

sev

ere

acn

e o

r var

icel

la

20 (1

6)

At

each

tr

eatm

ent

sess

ion

Scu

lptr

a In

ject

ion

s w

ere

giv

en

at 1

-mo

inte

rval

s to

p

rim

ary

end

po

int

of

reso

luti

on

of s

cars

(up

to

sev

en t

reat

men

ts)

1. In

vest

igat

or-

asse

ssed

re

du

ctio

n in

acn

e sc

ar s

ize

2. P

atie

nt-

asse

ssed

red

uct

ion

in

acn

e sc

ar s

ize

3. P

atie

nt

sati

sfac

tio

n

(Bee

r Sca

le)

AEs

wer

e lim

ited

to

dep

ress

ion

(n =

1) a

nd

no

t re

late

d to

tre

atm

ent.

Bu

rges

s et

al.,

20

05 P

MID

: 15

6924

67

USA

/HIV

-in

fect

ed m

en

on

HA

AR

T w

ith

faci

al

lipo

atro

ph

y

61

6, 1

8 m

o

New

-Fill

Stag

e I l

ipo

atro

ph

y, 4

.0–1

2.0

cc (n

= 9

)

Stag

e II

lipo

atro

ph

y, 8

.0–1

2.0

cc (n

= 1

5)

Stag

e III

lip

oat

rop

hy,

12.

0–24

.0 c

c

(n =

30)

Stag

e IV

lip

oat

rop

hy,

16.

0–24

.0 c

c (n

= 7

)

Inje

ctio

n to

th

e ju

nct

ion

o

f th

e su

bcu

tan

eou

s-

dee

p d

erm

al p

lan

e;

fan

nin

g in

ject

ion

te

chn

iqu

e w

as u

sed

to

crea

te a

dee

p d

erm

al

latt

ice

1. T

reat

men

t ev

alu

atio

n s

cale

2. P

hys

icia

n a

nd

no

ntr

eati

ng

p

hys

icia

n

No

t re

po

rted

Han

ke e

t al

., 20

07 P

MID

: 17

3731

69

USA

/27

HIV

-p

osi

tive

p

aten

ts a

nd

38

HIV

- neg

ativ

e p

atie

nts

65

2 yr

Sc

ulp

tra,

4–8

ml

Ch

eeks

Ef

ficac

y as

sess

men

t u

sin

g t

he

Faci

al L

ipo

atro

ph

y G

rad

ing

Sc

ale

(0–5

): 0

= n

o fa

cial

lip

oat

rop

hy

and

5 =

sev

ere

faci

al li

po

atro

ph

y

Pati

ent

sati

sfac

tio

n (1

–5):

1

= v

ery

un

sati

sfied

; 5

= v

ery

sati

sfied

61 p

atie

nts

(94%

) had

no

co

mp

licat

ion

s. B

oth

HIV

-p

osi

tive

an

d H

IV- n

egat

ive

pat

ien

ts h

ad s

imila

r co

mp

licat

ion

rate

s. Tw

o

pat

ien

ts w

ith

HIV

an

d

two

pat

ien

ts w

ith

ou

t h

ad

do

cum

ente

d p

apu

les

at

the

eyel

id m

arg

in. O

ne

pat

ien

t h

ad t

wo

sm

all

sub

cuta

neo

us

pap

ule

s at

th

e o

ral c

om

mis

sure

. Tw

o p

atie

nts

had

th

ree

pap

ule

s o

n t

he

chee

ks.

All

sub

cuta

neo

us

pap

ule

s re

solv

ed w

ith

tim

e w

ith

ou

t tr

eatm

ent.

Bas

ed o

n

Fish

er’s

exac

t te

st, H

IV-

neg

ativ

e p

atie

nts

do

no

t h

ave

sig

nifi

can

tly

gre

ater

n

um

ber

of c

om

plic

atio

ns

than

HIV

-po

siti

ve p

atie

nts

.

Salle

s et

al.,

20

08 P

MID

: 18

5513

41

Bra

zil/

Gen

eral

p

op

ula

tio

n

10

6, 3

6 m

o

Scu

lptr

a N

LFs,

on

e in

ject

ion

per

mo

fo

r 3 m

o

1. P

atie

nt

sati

sfac

tio

n2.

VA

S M

ino

r co

mp

licat

ion

s (e

dem

a an

d s

mal

l hem

ato

mas

) la

sted

on

ly 2

–10

day

s af

ter

the

inje

ctio

ns

and

reso

lved

sp

on

tan

eou

sly

wit

ho

ut

spec

ific

inte

rven

tio

ns.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

7

Kav

ou

ni e

t al

., 20

08 P

MID

: 18

4498

27

UK

/HIV

-po

siti

ve p

atie

nts

w

ith

faci

al li

po

atro

ph

y 441

3–32

mo

N

ew-F

ill

Min

imu

m 1

0 m

l in

ject

ed

into

faci

al a

reas

in

clu

din

g t

he

tem

ple

s, in

frao

rbit

al g

roov

es,

bu

ccal

are

as, N

LFs,

abov

e an

d b

elo

w t

he

zyg

om

a, a

nd

pre

par

oti

d

1. H

AD

S

2. A

pp

eara

nce

Sa

tisf

acti

on

Q

ues

tio

nn

aire

3. P

atie

nt

sati

sfac

tio

n

Rep

ort

ed A

Es d

uri

ng

th

e tr

eatm

ent

per

iod

wer

e m

inim

al a

nd

incl

ud

ed

inje

ctio

n s

ite

eryt

hem

a, te

nd

ern

ess,

edem

a, a

nd

ecc

hym

osi

s.

Inci

den

ce o

f no

du

le fo

rmat

ion

was

2.

9%.

Levy

et

al.,

2008

PM

ID:

1902

2099

USA

/HIV

-po

siti

ve a

nd

HIV

-neg

ativ

e p

atie

nts

65 (5

3)

3 yr

Sc

ulp

tra,

5.0

ml

Hal

f of t

he

volu

me

inje

cted

into

der

mis

, h

alf i

nto

th

e u

nd

erly

ing

su

bcu

tan

eou

s ti

ssu

e;

fou

r to

eig

ht

area

s o

n

each

ch

eek

1. E

valu

atio

n o

f fac

ial

lipo

atro

ph

y, n

et 3

-yr

imp

rove

men

t

2. P

atie

nt

sati

sfac

tio

n

At

2-yr

follo

w-u

p, 6

1 p

atie

nts

(94%

) h

ad n

o c

om

plic

atio

ns.

The

mo

st

com

mo

n c

om

plic

atio

n w

as

sub

cuta

neo

us

pap

ule

s, w

hic

h

dev

elo

ped

in fo

ur p

atie

nts

(6%

).

At

3-yr

follo

w-u

p, t

hre

e ad

dit

ion

al

pat

ien

ts d

evel

op

ed s

mal

l su

bcu

tan

eou

s p

apu

les.

The

tota

l nu

mb

er o

f PLL

A v

ials

re

ceiv

ed o

ver t

he

cou

rse

of t

he

trea

tmen

t w

as s

tro

ng

ly c

orr

elat

ed

wit

h t

he

dev

elo

pm

ent

of

sub

cuta

neo

us

pap

ule

s (p

< 0

.01)

.

The

vast

maj

ori

ty o

f pap

ule

s w

ere

no

t n

oti

ceab

le c

linic

ally

an

d o

nly

ap

pre

ciat

ed w

hen

pal

pat

ed.

Low

e et

al.,

20

09 P

MID

: 19

2073

24

UK

/Pat

ien

ts re

ceiv

ing

1–5

PLLA

tre

atm

ents

221

6–24

mo

Sc

ulp

tra

Ch

eeks

, per

iora

l, ch

in,

del

toid

s, th

igh

s, g

lute

al,

fore

hea

d

1. P

atie

nt-

rep

ort

ed

du

rati

on

of e

ffec

t In

ject

ion

-rel

ated

AEs

wer

e th

e m

ost

fr

equ

entl

y re

po

rted

, an

d m

ost

re

solv

ed s

po

nta

neo

usl

y w

ith

in 2

–7

day

s w

ith

no

furt

her

tre

atm

ent

req

uir

ed.

Clin

ical

ly re

leva

nt

pap

ule

s o

ccu

rred

, b

ut

the

maj

ori

ty w

ere

no

t vi

sib

le.

The

mai

n r

isk

for p

apu

les

or

no

du

les

wer

e th

e p

erio

rbit

al a

nd

p

erio

ral r

egio

ns.

The

auth

ors

cu

rren

tly

do

no

t re

com

men

d t

hes

e ar

eas.

Som

e n

od

ule

s to

ok

up

to

18 m

o to

reso

lve.

J Am AcAd dermAtol


Maz

zuco

et

al.,

2009

PM

ID:

1943

8668

Bra

zil/

Pati

ents

wit

h

on

e o

r mo

re o

f th

e fo

llow

ing

sig

ns

of

agin

g: c

uta

neo

us

flacc

idit

y, a

tro

ph

y, a

nd

w

rin

kles

in t

he

nec

k an

d c

hes

t

36

60 d

ays,

18

mo

A

vera

ge

3.9-

ml d

ose

in

ject

ed p

er

sess

ion

(n

= 3

6)

Nec

k an

d c

hes

t (p

rest

ern

al

area

); av

erag

e, 1

.8

sess

ion

s p

er p

atie

nt

1. Im

pro

vem

ent

bas

ed

on

ph

oto

gra

ph

ic

anal

ysis

per

form

ed

by

thre

e in

dep

end

ent

eval

uat

ors

at

60 d

ays

2. P

atie

nt

sati

sfac

tio

n

3. 1

8-m

o fo

llow

-up

Ap

pea

ran

ce o

f hem

ato

mas

an

d

ecch

ymo

sis

occ

urr

ed in

all

36 p

atie

nts

an

d re

gre

ssed

sp

on

tan

eou

sly

afte

r 7–1

0 d

ays.

On

e p

atie

nt

had

pal

pab

le n

od

ule

s, b

ut

this

pat

ien

t re

po

rted

no

t h

avin

g

mas

sag

ed t

he

area

acc

ord

ing

to

inst

ruct

ion

s.

Mes

t et

al.,

20

09 P

MID

: 19

2073

25

USA

/HIV

-po

siti

ve

pat

ien

ts

65

24 m

o

PLLA

, 1–1

0 m

l Pa

tien

ts t

reat

ed a

t 5-

wk

inte

rval

s u

nti

l fu

ll co

rrec

tio

n w

as o

bta

ined

1. P

atie

nt

sati

sfac

tio

n

(1–5

, wit

h 5

bei

ng

ve

ry s

atis

fied

)

2. N

um

ber

of

retr

eatm

ents

req

uir

ed

No

ser

iou

s A

Es

Neg

red

o e

t al

., 20

06 P

MID

: 17

1921

48

Spai

n/H

IV-i

nfe

cted

p

atie

nts

pre

sen

tin

g

wit

h a

nti

retr

ovir

al-

asso

ciat

ed fa

cial

lip

oat

rop

hy

for >

6 m

o 13

8 (e

igh

t re

ceiv

ed

fat,

25 re

ceiv

ed

PLLA

, an

d

105

rece

ived

p

oly

acry

lam

ide

gel

)

96 w

k A

nal

og

ou

s fa

t o

bta

ined

by

lipo

suct

ion

, 50

ml

Poly

lact

ic a

cid,

3–

14 m

l

Poly

acry

lam

ide

gel

, 4–1

8 m

l

NLF

s Le

vel o

f fac

ial

lipo

atro

ph

y fr

om

p

ho

tog

rap

hic

an

d

self-

ass

essm

ent

All

pat

ien

ts c

om

pla

ined

of p

ain

at

the

infil

trat

ion

sit

e d

uri

ng

th

e in

terv

enti

on

, an

d fa

cial

ed

ema

for 2

–3 d

ays,

wh

ich

was

alw

ays

min

imal

an

d t

ran

sien

t. Ec

chym

ose

s w

ere

ob

serv

ed in

14%

of p

atie

nts

, m

ost

cas

es (1

3%) b

ein

g in

th

e p

oly

acry

lam

ide

gro

up

. Sev

en

of 2

1 w

om

en (3

3%) i

ncl

ud

ed

in t

he

po

lyac

ryla

mid

e g

rou

p

man

ifest

ed e

cch

ymo

ses.

All

case

s re

solv

ed s

po

nta

neo

usl

y w

ith

in 3

–5 d

ays.

Two

pat

ien

ts

fro

m t

he

PLLA

gro

up

(1.4

% o

f th

e to

tal n

um

ber

of p

atie

nts

in

clu

ded

) pre

sen

ted

pal

pab

le

sub

cuta

neo

us

mic

ron

od

ule

s in

th

e m

alar

are

a, a

nd

tw

o s

ub

ject

s fr

om

th

e p

oly

acry

lam

ide

gro

up

(1

.4%

of t

he

tota

l) d

evel

op

ed a

su

per

ficia

l cu

tan

eou

s in

fect

ion

, w

hic

h w

as e

asily

co

ntr

olle

d w

ith

an

ora

l an

tib

ioti

c (t

he

spec

ific

typ

e o

f bac

teri

a w

as n

ot

iden

tifie

d).

On

ly t

wo

pat

ien

ts re

qu

ired

w

ith

dra

wal

of t

he

sub

stan

ce a

fter

p

oly

acry

lam

ide

infil

trat

ion

bec

ause

o

f a h

yper

corr

ecti

on

or e

xces

s o

f su

bst

ance

in t

he

mal

ar a

rea

(on

e m

an a

nd

on

e w

om

an).



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Sad

ick

et a

l.,

2008

PM

ID:

1901

6062

USA

/Gen

eral

po

pu

lati

on

26

6–12

mo

PL

LA, 1

.5–2

.0

ml

Han

d: m

ean

, 2.3

8 tr

eatm

ents

per

pat

ien

t N

ot

rep

ort

ed

The

mo

st c

om

mo

nly

rep

ort

ed A

Es,

such

as

bru

isin

g, s

wel

ling,

an

d p

ain

, w

ere

inje

ctio

n-r

elat

ed a

nd

reso

lved

w

ith

in a

few

day

s o

f tre

atm

ent.

No

p

apu

les

or n

od

ule

s w

ere

rep

ort

ed

in a

ny

pat

ien

ts, a

nd

th

ere

wer

e n

o

seri

ou

s A

Es.

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

19

Ap

ikia

n e

t al

., 20

07

PMID

: 175

2412

5 A

ust

ralia

/Fo

ur w

hit

e w

om

en

aged

48–

57 y

r 4

7 d

ays–

2 yr

N

ew-F

ill

Rep

ort

1: I

nfr

aorb

ital

are

as,

tem

po

ral a

reas

, ch

eek

area

Rep

ort

2: E

ach

infr

aorb

ital

re

gio

n a

nd

nas

ola

bia

l lin

e

Rep

ort

3: I

nfr

aorb

ital

ar

ea, n

aso

jug

al li

nes

, m

ario

net

te li

nes

in fi

rst

trea

tmen

t, in

frao

rbit

al

area

, ch

eek

bo

ne

area

, an

d m

ario

net

te li

nes

6

wk

late

r

Rep

ort

1: S

ever

al fi

rm 1

- to

2-m

m

asym

pto

mat

ic n

od

ule

s in

th

e in

frao

rbit

al a

reas

6 w

k af

ter

trea

tmen

t

Rep

ort

2: T

hre

e as

ymp

tom

atic

firm

n

od

ule

s ~

3 m

m w

ith

in 7

day

s o

f th

e p

roce

du

re

Rep

ort

3: P

alp

able

3-m

m

asym

pto

mat

ic n

od

ule

aft

er 6

wk

Rep

ort

4: T

hre

e as

ymp

tom

atic

n

od

ule

s 7–

10 d

ays

afte

r tre

atm

ent

Bee

r, 20

09 P

MID

: 19

2073

33

USA

/64-

yr-o

ld w

om

an fo

r co

smet

ic t

reat

men

t o

f p

erio

rbit

al a

reas

, 59-

yr-

old

wo

man

eva

luat

ed fo

r fa

cial

reju

ven

atio

n

USA

/59-

yr-o

ld w

om

an fo

r tr

eatm

ent

of m

idfa

ce

des

cen

t

2 (2

) 12

–18

mo

PL

LA, 2

.0 m

l eac

h te

ar t

rou

gh

, tw

o s

essi

on

s, 4

wk

apar

tPL

LA, 1

.0 m

l, ea

ch te

ar t

rou

gh

Dep

ot

inje

ctio

ns

into

eac

h

tear

tro

ug

h m

ade

at t

he

leve

l of t

he

per

iost

eum

Inje

ctio

ns

into

th

e ch

eeks

, te

ar t

rou

gh

s, an

d

zyg

om

atic

arc

h a

reas

No

t re

po

rted

D

evel

op

men

t o

f su

bcu

tan

eou

s p

apu

les

cau

sed

by

a fo

reig

n b

od

y re

acti

on

Den

se fo

reig

n b

od

y re

acti

on

wit

h

abu

nd

ant

form

atio

n o

f co

llag

en

Bel

jaar

ds

et a

l.,

2005

PM

ID:

1602

9705

The

Net

her

lan

ds/

Thre

e w

om

en a

ged

35–

53 y

r 3

12–2

2 m

o

1–3

ml r

eco

nst

itu

ted

New

-Fill

(p

oly

lact

ic a

cid

) N

LFs,

chee

ks, l

ips,

nec

k Pa

lpab

le s

tran

ds

on

th

e N

LF, s

tran

ds

and

no

du

les

alo

ng

tre

ated

w

rin

kles

, pal

pab

le s

up

erfic

ial

no

du

les

aro

un

d t

reat

men

t si

te

Bu

rges

s, 20

08 P

MID

: 18

2317

00

USA

/69-

yr-o

ld A

fric

an

Am

eric

an w

om

an

1 18

mo

Sc

ulp

tra,

5 m

l eac

h t

reat

men

t, tw

o t

reat

men

ts to

tal

Der

mal

su

bcu

tan

eou

s p

lan

e o

f th

e u

pp

er a

nd

lo

wer

ch

eeks

an

d t

he

pre

auri

cula

r an

d m

alar

re

gio

ns

No

t re

po

rted

N

on

e re

po

rted

J Am AcAd dermAtol


Ham

ilto

n e

t al

., 20

08 P

MID

: 18

0530

31

Fran

ce/5

8-yr

-old

im

mu

no

com

pet

ent

wo

man

pre

sen

ted

wit

h

sub

cuta

neo

us

no

du

les

1 4

yr

Scu

lptr

a, 9

ml

NLF

s (6

ml)

Cu

tan

eou

s b

ord

er o

f th

e ve

rmili

on

(1 m

l)

Jug

om

alar

dep

ress

ion

ad

jace

nt

to t

he

infr

aorb

ital

per

iost

eum

No

t re

po

rted

Pr

esen

ted

wit

h te

nd

er n

od

ule

s at

inje

ctio

n s

ites

; was

tre

ated

w

ith

intr

ales

ion

al t

riam

cin

olo

ne

inje

ctio

ns.

Aft

er s

ever

al m

on

ths,

exam

inat

ion

re

veal

ed s

ever

al re

d, n

on

ten

der

, d

eep

no

du

les,

and

faci

al s

kin

at

rop

hy

and

tela

ng

iect

asia

s.

No

du

les

per

sist

ed a

nd

pat

ien

t ev

entu

ally

was

tre

ated

wit

h

tria

mci

no

lon

e at

40

mg

/ml t

o

reso

lve

the

infla

mm

atio

n.

Jham

et

al.,

2009

PM

ID: 1

9138

600

Vari

ou

s/G

ener

al p

op

ula

tio

n

56

Vari

ou

s U

pp

er/l

ow

er li

p, N

LF, c

hee

k N

ot

rep

ort

ed

Clin

ical

pre

sen

tati

on

: Sin

gle

no

du

le,

diff

use

sw

ellin

g, m

ult

iple

no

du

les,

mas

s, o

ther

Trea

tmen

ts: E

xcis

ion

al b

iop

sy,

ster

oid

s (s

yste

mic

an

d

intr

ales

ion

al),

anti

bio

tics

, n

on

ster

oid

al a

nti

infla

mm

ato

ry

dru

gs,

uri

cosu

ric

agen

t, im

mu

no

reg

ula

tor

Kat

es e

t al

., 20

08

PMID

: 190

8355

2 U

SA/T

wo

wh

ite

men

in

thei

r 40s

wit

h fa

cial

lip

oat

rop

hy

wh

o h

ad

bee

n H

IV-p

osi

tive

for

>10

yr

2 12

mo

PL

LA

Dee

p d

erm

is o

r su

bcu

tan

eou

s la

yer o

f th

e fa

ce, t

wo

via

ls in

ea

ch o

f five

tre

atm

ents

sp

aced

4 w

k ap

art

No

t re

po

rted

Tr

eatm

ents

ass

oci

ated

wit

h m

ild

swel

ling

th

at re

solv

ed w

ith

in 5

–7

day

s, b

ruis

ing

was

no

t o

bse

rved

, n

o p

apu

les

wer

e re

po

rted

in t

he

follo

w-u

p p

erio

d o

f 12

mo.

Lom

bar

di e

t al

., 20

04 P

MID

: 14

7201

98

Fran

ce/P

atie

nts

wit

h

Art

eco

ll, D

erm

aliv

e,

New

-Fill

, or L

iqu

id-

Silic

on

e in

du

ced

g

ran

ulo

mas

11

No

t re

po

rted

A

rtec

oll

Der

mal

ive

New

-Fill

Liq

uid

-Sili

con

e

No

t re

po

rted

N

ot

rep

ort

ed

12 b

iop

sy s

pec

imen

s ta

ken

: lip

s

(n =

6),

chee

ks (n

= 2

), n

aso

lab

ial

fold

s (n

= 1

), g

lab

ella

(n =

2),

and

lo

wer

eye

lid (n

= 1

).

All

wer

e ei

ther

CFB

Gs

or C

MG

s.

All

lesi

on

s w

ere

asym

pto

mat

ic.

Diff

eren

t ty

pes

of C

FBG

s w

ere

rela

ted

to

var

iou

s fil

lers

: Ty

pe

1: A

rtec

oll

or A

rtep

last

Ty

pe

2: D

erm

aliv

e Ty

pe

3: N

ew-F

illTy

pe

4: B

iop

last

iqu

e.

CM

Gs

wer

e as

soci

ated

wit

h

Liq

uid

- Sili

con

e in

ject

ion

s.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Mes

t et

al.,

200

6 PM

ID: 1

7083

585

USA

/Pat

ien

ts o

lder

th

an 1

8 w

ith

HIV

ser

op

osi

tivi

ty

and

faci

al li

po

atro

ph

y

97 (7

5)

12 m

o

PLLA

, 1–6

ml p

er s

essi

on

, wit

h

pat

ien

ts re

ceiv

ing

bet

wee

n

on

e an

d s

ix s

essi

on

s

Ch

eeks

an

d te

mp

les

Incr

ease

in

tota

l cu

ta-

neo

us

thic

k nes

s b

y sk

in

calip

ers

Pati

ent

sati

sfac

tio

n

on

a 1

–5

scal

e

No

ne

rep

ort

ed

Pove

da

et a

l., 2

006

PMID

: 163

8828

5 Sp

ain

/55-

yr-o

ld w

om

an,

72-y

r-o

ld w

om

an,

70-y

r-o

ld w

om

an,

54-y

r-o

ld w

om

an,

43-y

r-o

ld w

om

an

5 1

mo

B

otu

linu

m to

xin

typ

e A

(Bo

tox)

(n

= 1

)

Co

llag

en (n

= 1

)

Dim

eth

ylp

oly

silo

xan

e (s

ilico

ne)

(n =

3)

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er li

p,

nas

og

enia

n a

rea,

faci

al

area

, ch

eeks

, ch

in, a

nd

b

ucc

al m

uco

sa

Dis

cret

e tr

abec

ula

tio

n o

f th

e m

and

ibu

lar a

nd

su

bm

and

ibu

lar

sub

cuta

neo

us

fat

rela

ted

to

infla

mm

atio

n c

han

ges

; in

ten

se

infla

mm

ato

ry p

roce

sses

aff

ecti

ng

al

mo

st t

he

enti

re s

ub

cuta

neo

us

cellu

lar t

issu

e co

veri

ng

th

e m

axill

ae a

nd

th

e flo

or o

f th

e m

ou

th a

nd

a la

rge

par

t o

f th

e b

ucc

al m

uco

sa; g

ener

aliz

ed,

bila

tera

l, fa

cial

tu

mef

acti

on

.; sw

ellin

g o

f th

e lip

s an

d c

hee

ks

Ral

sto

n e

t al

., 20

06

PMID

: 173

7315

1 U

SA/4

0-yr

-old

w

hit

e w

om

an

1 10

mo

Sc

ulp

tra

Up

per

arm

Ve

ry m

ino

r ten

der

nes

s an

d e

ryth

ema

Red

aelli

, 200

6 PM

ID:

1717

7745

It

aly/

Fem

ale

pat

ien

ts a

ged

b

etw

een

59

and

72

yr

27

6–15

mo

PL

LA, 2

ml p

er h

and

in t

he

first

ses

sio

n, 1

–2 m

l fo

r su

bse

qu

ent

sess

ion

s

Do

rsu

m o

f th

e h

and

Pa

tien

t sa

tisf

acti

on

sc

ore

an

d

ph

ysic

ian

sa

tisf

acti

on

sc

ore

usi

ng

a

defi

nit

ive

gra

du

ated

sc

ore

On

e p

atie

nt

exp

erie

nce

d n

od

ule

fo

rmat

ion

th

at d

isap

pea

red

w

ith

ou

t tr

eatm

ent.

Ren

do

n e

t al

., 20

08

PMID

: 184

4184

3 U

SA/6

4-yr

-old

wo

man

wh

o

un

der

wen

t ex

ten

sive

su

rgic

al p

roce

du

res

for d

amag

e to

th

e cr

anio

faci

al a

rea

follo

win

g

a ca

r acc

iden

t

1 5

mo

PL

LA, 5

ml

Dee

p d

erm

is o

f th

e ch

eeks

(2

ml);

NLF

s (1

ml),

zy

go

mat

ic a

rch

es (1

ml),

te

mp

les

(0.5

ml),

an

d

chin

(0.5

ml)

Ab

ove

trea

tmen

t re

pea

ted

tw

o m

ore

tim

es ~

1 m

o

apar

t

Pati

ent’s

q

ual

ify o

f lif

e

No

ne

rep

ort

ed

J Am AcAd dermAtol


Res

zko

et

al.,

2009

PM

ID: 1

9207

329

USA

/62-

yr-o

ld

imm

un

oco

mp

eten

t p

atie

nt

1 (1

) 12

–18

mo

sin

ce

trea

tmen

t Sc

ulp

tra

(PLL

A)

Bila

tera

l ch

eeks

, ch

in, a

nd

in

frao

rbit

al a

reas

N

ot

rep

ort

ed

>60

firm

2- t

o 1

8-m

m p

apu

les

and

n

od

ule

s o

n b

ilate

ral c

hee

ks, c

hin

, an

d in

frao

rbit

al a

reas

No

du

les

con

tain

ed fo

reig

n b

od

y g

ran

ulo

mas

of i

rreg

ula

rly

shap

ed

po

lari

zab

le c

ryst

als.

Ro

ssn

er e

t al

., 20

09

PMID

: 192

5016

0 G

erm

any/

Pati

ents

fro

m

Ber

lin R

egis

try

pre

sen

tin

g

an a

dve

rse

reac

tio

n to

PL

LA

22

8 yr

N

ew-F

ill

No

t re

po

rted

N

ot

rep

ort

ed

Mo

st s

ever

e A

E w

as n

od

ule

fo

rmat

ion

, rat

ed a

s se

vere

in 1

3 (5

9.1%

) cas

es.

Usu

ally

, th

e n

od

ule

s to

ok

seve

ral

mo

nth

s to

dev

elo

p a

nd

per

sist

ed

mo

re t

han

1 y

r in

mo

st p

atie

nts

.

The

freq

uen

cy o

f pat

ien

ts w

ith

AEs

d

ecre

ased

in t

he

per

iod

fro

m

2000

to 2

007.

Sch

ulm

an e

t al

., 20

08 P

MID

: 18

1868

71

USA

/63-

yr-o

ld t

hin

wo

man

w

ho

co

mp

lain

ed o

f a

sup

erio

r “st

ep-o

ff”

def

orm

ity

and

vis

ible

in

terc

ost

al s

pac

es a

fter

im

pla

nt

reco

nst

ruct

ion

1 9

mo

Sc

ulp

tra:

Fo

ur t

reat

men

ts

at 1

-mo

inte

rval

s, ea

ch

trea

tmen

t w

as t

wo

367

.5-

mg

via

ls

Sub

cuta

neo

us

tiss

ue

and

d

eep

der

mal

laye

rs o

f th

e su

per

ior a

nd

med

ial

rig

ht

ches

t w

all

No

t re

po

rted

N

on

e re

po

rted

Stew

art

et a

l., 2

007

PMID

: 176

6710

2 U

SA/3

9-yr

-old

wo

man

p

rese

nte

d w

ith

mu

ltip

le

visi

ble

, pal

pab

le p

apu

les

in b

ilate

ral i

nfr

aorb

ital

re

gio

n

1 4

mo

Sc

ulp

tra

Bila

tera

l in

frao

rbit

al re

gio

n

No

t re

po

rted

3–

4 d

ays

afte

r tre

atm

ent,

bu

mp

s d

evel

op

ed a

lon

g t

he

orb

ital

rim

an

d n

asal

sid

ewal

l; tr

eatm

ent

over

th

e n

ext

3 m

o w

ith

intr

ales

ion

al

tria

mci

no

lon

e ac

eto

nid

e (3

mg

/m

l) d

id n

ot

imp

rove

th

e b

um

ps.

Bio

psy

reve

aled

fore

ign

bo

dy

gra

nu

lom

ato

us

reac

tio

n p

atte

rn.

Res

tyla

ne

was

inje

cted

in t

he

tear

tr

ou

gh

to c

amo

ufla

ge

pap

ule

s, b

ut

this

mad

e th

em m

ore

ap

par

ent.

Surg

ical

exc

isio

n w

as u

sed

to re

mov

e th

e p

apu

les.



pp

end

ix B

. Co

nt’d

PM

MA

Fill

ers

Ran

do

miz

ed C

on

tro

lled

Tri

al: N

o. o

f S

tud

ies,

2

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Co

hen

et

al.,

2004

PM

ID:

1546

8406

USA

/Pat

ien

ts a

t le

ast

18 y

r old

pre

sen

tin

g

for g

lab

ella

r, N

LFs,

rad

ial u

pp

er li

p li

nes

, m

ario

net

te li

nes

co

rrec

tio

n

251

(251

) (11

1 at

12

mo

) 1,

3, 6

, 12

mo

A

rtec

oll

(n =

128

)

Zyd

erm

II o

r Zyp

last

(n

= 1

23)

Tun

nel

ing

tech

niq

ue:

g

lab

ella

, NLF

s, ra

dia

l u

pp

er li

p li

nes

, m

ario

net

te li

nes

1. C

osm

etic

co

rrec

tio

n a

t 6

and

12

mo

usi

ng

th

e Fa

cial

Fo

ld A

sses

smen

t Sc

ale

by

thre

e m

aske

d o

bse

rver

s an

d

ph

ysic

ian

s

2. P

hys

icia

n a

nd

pat

ien

t as

sess

men

t

27 A

Es in

Art

eco

ll g

rou

p; 3

8 A

Es in

co

llag

en c

on

tro

l g

rou

p

Co

hen

et

al.,

2006

PM

ID:

1693

6546

USA

/Pat

ien

ts w

ith

w

rin

kles

of t

he

gla

bel

la,

nas

ola

bia

l fo

lds,

rad

ial

up

per

lip

lin

es, a

nd

co

rner

s o

f th

e m

ou

th;

trea

ted

wit

h P

MM

A

fille

r in

piv

ota

l RC

T (C

oh

en 2

004)

251

(233

) 69

4–5

yr)

1, 3

, 6, 1

2 m

o;

4–5

yr

Art

eFill

(am

ou

nt

no

t sp

ecifi

ed) (

n =

128

)

Co

llag

en (a

mo

un

t n

ot

spec

ified

) (n

= 1

23)

Inje

ctio

n a

t th

e g

lab

ella

, N

LFs,

rad

ial u

pp

er li

p

lines

, or c

orn

ers

of t

he

mo

uth

1. C

osm

etic

co

rrec

tio

n

2. P

hys

icia

n’s

asse

ssm

ent

of

succ

ess

3. F

acia

l Fo

ld A

sses

smen

t Sc

ale

rati

ng

4. L

on

g-t

erm

co

smet

ic

corr

ecti

on

5. P

hys

icia

n’s

asse

ssm

ent

of

lon

g-t

erm

su

cces

s

6. S

afet

y an

d A

E

1. R

edn

ess,

swel

ling,

an

d

lum

pin

ess

at t

he

inje

ctio

n

site

for c

olla

gen

2. 2

7 ad

vers

e ev

ents

for

Art

eFill

vs.

38 a

dve

rse

even

ts fo

r co

llag

en

3. S

ix la

te a

dve

rse

even

ts fo

r A

rteF

ill: t

wo

sev

ere

and

fou

r m

od

erat

e

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Wo

erle

et

al.,

2004

PM

ID: 1

5303

782

Euro

pe/

300

pat

ien

ts (7

0%

men

) fo

r pro

spec

tive

, 48

-yr-

old

man

an

d

51-y

r-o

ld w

om

an fo

r re

tro

spec

tive

cas

e re

po

rt 30

2 12

–24

mo

PL

LA

26-g

aug

e n

eed

le in

to

the

nas

ola

bia

l fo

lds,

mar

ion

ette

lin

es,

lab

iom

enta

l cre

ases

, u

pp

er li

p, c

hee

ks, c

hin

, an

d te

mp

les

Fro

m 1

999–

2002

, th

e ac

id

mix

ture

sto

od

for 2

–12

hr b

efo

re in

ject

ion

; af

terw

ard,

th

e m

ixtu

re

sto

od

for 3

6–48

hr.

Pati

ent

sati

sfac

tio

n

In t

he

first

par

t o

f th

e st

ud

y, 1

0%

dev

elo

ped

su

bcu

tan

eou

s p

apu

les

that

reso

lved

in 1

2–24

mo

w

ith

ou

t tr

eatm

ent

and

3 m

o w

ith

tr

eatm

ent.

Wo

lfram

et

al.,

2006

PM

ID: 1

7135

735

Au

stri

a/Tw

o 5

8-yr

-old

w

om

en, o

ne

53-y

r-o

ld

wo

man

3 3

mo

–2 y

r N

ew-F

ill, R

esty

lan

e, D

erm

aLiv

e Z

ygo

mat

ic a

rch

, eye

lids,

fore

hea

d, n

aso

lab

ial

fold

s, ch

eeks

Eryt

hem

ato

us

ind

ura

tio

ns

at

inje

ctio

n s

ites

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D, A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

PLL

A, p

oly

-L-l

acti

c ac

id; P

MID

, Pu

bM

ed id

enti

ficat

ion

nu

mb

er; U

SA, U

nit

ed S

tate

s; H

IV, h

um

an im

mu

no

defi

cien

cy v

iru

s;

AEs

, ad

vers

e ev

ents

; VA

S, v

isu

al a

nal

og

ue

scal

e; H

AD

S, H

osp

ital

An

xiet

y an

d D

epre

ssio

n S

cale

; HA

AR

T, h

igh

ly a

ctiv

e an

tire

trov

iral

th

erap

y; N

LF, n

aso

lab

ial f

old

; CFB

Gs,

clas

sic

fore

ign

bo

dy

typ

e g

ran

ulo

mas

; C

MG

s, cy

stic

an

d m

acro

ph

agic

-typ

e g

ran

ulo

mas

.

J Am AcAd dermAtol


Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

1

Co

hen

et

al.,

2007

PM

ID:

1808

6062

USA

/Pat

ien

ts t

reat

ed w

ith

PM

MA

fille

r in

piv

ota

l R

CT

(Co

hen

, 200

4)

251

(145

)5

yrA

rteF

ill, 0

.82

ml/

fold

(n

= 1

28)

NLF

1. B

lind

ed o

bse

rver

FFA

ra

tin

gs

at 5

yr c

om

par

ed to

b

asel

ine

2. In

vest

igat

or F

FA s

core

s3.

Inve

stig

ato

r su

cces

s ra

te4.

Pat

ien

t sa

tisf

acti

on

5. E

ffica

cy a

t 5

yr

145

sub

ject

s w

ere

eval

uat

ed

for s

afet

y; 2

8 to

tal a

dve

rse

wer

e ex

per

ien

ced

by

21

sub

ject

s; 2

0 tr

eatm

ent-

rela

ted

AEs

wer

e d

istr

ibu

ted

am

on

g 1

5 su

bje

cts.

Mo

st

com

mo

n w

as lu

mp

ines

s;

80%

wer

e d

eem

ed m

ild.

Trea

tmen

t-re

late

d e

ven

ts:

Mild

: 8.3

% M

od

erat

e: 1

.4%

Se

vere

: 0.7

%Se

vere

eve

nt:

Lum

py,

infla

med

n

od

ule

in e

ach

of t

he

NLF

s at

5 y

r. A

ffec

ted

are

a p

arti

ally

resp

on

ded

to

intr

ales

ion

al s

tero

id t

her

apy

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

10

Bed

ocs

et

al.,

2008

PM

ID:

1844

1850

USA

/Wo

man

pre

sen

ted

w

ith

a 3

-mo

his

tory

o

f an

ery

them

ato

us

pru

riti

c p

laq

ue

loca

ted

in

th

e ar

ea o

f an

u

nco

nven

tio

nal

invi

sib

le

tatt

oo

pla

ced

on

th

e u

pp

er a

rm

19

mo

sin

ce

pro

ced

ure

PMM

A w

ith

flu

ore

scen

t d

yeU

pp

er a

rmN

ot

rep

ort

edPh

ysic

al e

xam

inat

ion

reve

aled

a

6.5-

cm e

ryth

emat

ou

s p

laq

ue

of c

oal

esci

ng

firm

p

apu

les

in t

he

shap

e o

f a

styl

ized

su

n lo

cate

d o

n le

ft

late

ral a

rm

His

tolo

gic

exa

min

atio

n

dis

clo

sed

that

the

epid

erm

is

app

eare

d u

nch

ang

ed, t

he

der

mis

co

nta

ined

mu

ltip

le

epit

hel

ioid

gra

nu

lom

as

surr

ou

nd

ed b

y a

spar

se

lym

ph

ocy

tic

infil

trat

e; s

mal

l, cl

ear s

ph

eric

al, p

arti

cles

w

ith

so

me

vari

atio

n in

siz

e an

dsh

ape

wer

e p

rese

nt

wit

hin

th

ese

gra

nu

lom

as..

Para

ffin

-em

bed

ded

sec

tio

n

fluo

resc

ed u

nd

er W

oo

d

lam

p e

xam

inat

ion



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Car

valh

o e

t al

., 20

09 P

MID

: 19

4386

69

Bra

zil/

Men

an

d w

om

en

wit

ho

ut

pre

vio

us

faci

al a

ug

men

tati

on

tr

eatm

ents

, 30%

(n =

79

) wit

h fa

cial

atr

op

hy

cau

sed

by

AID

S,

60%

(n =

159

) wit

h

ph

oto

agin

g s

ign

s, 9%

(n

= 5

) wit

h d

epre

ssed

b

ut

dis

ten

sib

le s

cars

, an

d 1

% (n

= 3

) wit

h

resi

du

al d

epre

ssio

ns

fro

m c

uta

neo

us

lup

us

pro

fun

du

s

154

wo

men

, 112

m

en

1 m

o a

nd

6

mo

aft

er

trea

tmen

t, an

d t

hen

ea

ch y

ear

for 9

yr

Met

aCri

ll (P

MM

A),

1–8

ml d

epen

din

g o

n

pat

ien

t

bet

wee

n a

pp

licat

ion

s

24-,

23-,

or 2

6-g

aug

e n

eed

les

use

d, p

rod

uct

in

sert

ed a

t th

e su

bcu

tan

eou

s ti

ssu

e o

r su

bd

erm

al la

yer

Sess

ion

s va

ried

fr

om

on

e to

fou

r, w

ith

in in

terv

als

of

app

roxi

mat

ely

40–6

0 d

ays

Sati

sfac

tio

n w

ith

tre

atm

ent

and

imp

rove

men

t in

sel

f-

este

em

Tem

po

rary

sw

ellin

g, e

ryth

ema,

an

d b

ruis

ing

Cas

tro

et

al.,

2007

PM

ID:

1827

8234

Bra

zil/

77-y

r-o

ld o

man

1

Un

rep

ort

ed

nu

mb

er o

f d

ays

PMM

AN

aso

gen

ian

gro

ove

No

t re

po

rted

Pres

ente

d w

ith

faci

al p

ain

, ed

ema,

an

d c

yan

osi

s in

rig

ht

hem

iface

24

hr

afte

r tre

atm

ent;

furt

her

d

evel

op

ed in

to fa

cial

n

ecro

sis

in t

he

area

s n

ou

rish

ed b

y th

e ri

gh

t in

feri

or a

nd

su

per

ior l

abia

l co

ron

al a

rter

ies

and

th

e ri

gh

t an

gu

lar a

rter

ies

da

Co

sta

Mig

uel

et

al.,

2009

PM

ID:

1924

3914

Bra

zil/

56-y

r-o

ld w

om

an

pre

sen

ted

wit

h s

wel

ling

in

th

e lo

wer

lip

1C

ase pre

sen

ted

1

yr a

fter

tr

eatm

ent

PMM

ALi

pN

ot

rep

ort

edFi

rm p

ink

no

du

le c

over

ed

wit

h n

on

ulc

erat

ed m

uco

sa,

loca

ted

in t

he

rig

ht

ante

rio

r in

feri

or a

lveo

lar

mu

cosa

; bio

psy

resu

lts

no

te

pre

sen

ce o

f fo

reig

n b

od

y g

ran

ulo

ma.

Gel

fer e

t al

., 20

07 P

MID

: 17

4515

87

USA

/Gen

eral

po

pu

lati

on

10U

p to

3 y

r10

cas

es p

rese

nte

dVa

rio

us

site

sN

/A10

cas

es p

rese

nte

d w

ith

in

flam

mat

ory

reac

tio

ns,

incl

ud

ing

gra

nu

lom

as,

no

du

les,

and

ind

ura

tio

n.

Oth

er a

dve

rse

even

ts in

clu

de

eryt

hem

a,sw

ellin

g, p

ain

, an

d d

isco

lora

tio

n.

Ad

vers

e re

acti

on

on

set

vari

ed

fro

m 3

mo

to 4

yr a

fter

last

in

ject

ion

.

J Am AcAd dermAtol


Jham

et

al.,

PMID

: 19

1386

00Va

rio

us/

Gen

eral

p

op

ula

tio

n56

Vari

ou

sU

pp

er/l

ow

er li

p, N

LF,

chee

k N

ot

rep

ort

edC

linic

al p

rese

ntat

ion:

Sin

gle

no

dul

e, d

iffus

e sw

ellin

g,

mul

tiple

nod

ules

, mas

s, ot

her

Trea

tmen

ts: E

xcis

ion

al

bio

psy

, ste

roid

s (s

yste

mic

an

d in

tral

esio

nal

), an

tib

ioti

cs, n

on

ster

oid

al

- an

tiin

flam

mat

ory

d

rug

s, u

rico

suri

c ag

ent,

imm

un

ore

gu

lato

r

Nel

son

et

al.,

2008

PM

ID:

1802

3267

UK

/Pat

ien

ts w

ith

H

IV- a

sso

ciat

ed

lipo

dys

tro

ph

y

46 (4

6)R

ang

e, 1

–14

mo

Co

lem

an a

uto

log

ou

s fa

t in

ject

ion

(n =

26)

New

-Fill

(n =

10)

Bio

-Alc

amid

(n =

8)

Trea

tmen

t (e

.g.,

lipo

suct

ion

) fo

r fat

ac

cum

ula

tio

n(n

= 1

3) (r

esu

lts

no

t p

rovi

ded

for t

his

re

view

)

New

-Fill

inje

ctio

ns

wer

e p

erfo

rmed

b

y a

trai

ned

nur

se

spec

ialis

t. O

ne

vial

of

New

-Fill

per

ch

eek

was

in

ject

ed to

the

dee

p

der

mis

of a

ffec

ted

ar

eas

(i.e.

, ch

eek,

te

mp

le) d

urin

g e

ach

tr

eatm

ent s

essi

on.

Bio

-Alc

amid

inje

ctio

ns

wer

e p

erfo

rmed

in a

th

eate

r env

iro

nm

ent.

The

pro

du

ct w

as

inje

cted

un

til t

ota

l co

rrec

tio

n o

f th

e d

efici

t w

as o

bta

ined

1. P

atie

nt

sati

sfac

tio

n s

core

u

sin

g a

vis

ual

an

alo

gu

e sc

ale

2. C

hee

k vo

lum

e u

sin

g 3

D

faci

al im

age

scan

(on

ly

per

form

ed in

pat

ien

ts

Au

tolo

go

us

fat:

Bru

isin

g a

nd

sw

ellin

g o

ccu

rred

in fi

ve

pat

ien

ts p

ost

op

erat

ivel

y.N

ew-F

ill: N

on

e re

po

rted

.B

io-A

lcam

id: C

om

plic

atio

ns

incl

ud

ed b

ruis

ing

an

d

swel

ling

per

sist

ing

up

to

1 m

o. T

wo

pat

ien

ts h

ad

min

or a

sym

met

ry re

qu

irin

g

corr

ecti

ve p

roce

du

res.

Para

da

et a

l.,

2005

PM

ID:

1627

6149

Bra

zil

11N

ot

rep

ort

edR

esty

lan

e (h

yalu

ron

ic

acid

), M

etaC

rill

po

lym

eth

yl-

met

hac

ryla

te),

Aq

uam

id

(po

lyac

ryla

mid

e),

New

-Fill

(po

lyla

ctic

ac

id),

Art

eco

ll PM

MA

su

spen

ded

in

a c

olla

gen

so

luti

on

).

Bio

psy

sp

ecim

ens

fixed

in

10%

form

alin

.R

esty

lan

e: A

n in

flam

mat

ory

p

roce

ss o

ccu

rred

on

th

e d

eep

reti

cula

r der

mis

, h

ypo

der

mis

, an

d a

t th

e le

vel o

f th

e d

erm

al

mu

scu

latu

re. P

eria

dn

exal

an

d p

eriv

ascu

lar

lym

ph

om

on

on

ucl

ear

infil

trat

es w

ere

ob

serv

ed

in t

he

sup

erfic

ial a

nd

dee

p

der

mis

, in

ad

dit

ion

to

nu

mer

ou

s eo

sin

op

hils

.

Aq

uam

id: I

nfla

mm

ato

ry

infil

trat

es w

ere

ob

serv

ed o

n

the

dee

p re

ticu

lar d

erm

is,

hyp

od

erm

is, a

nd

der

mal

m

usc

ula

ture

.

Met

aCri

ll: A

foca

l or d

iffu

se

infla

mm

ato

ry in

filtr

ate

at

the

reti

cula

r der

mis

an

d

hyp

od

erm

is w

as o

bse

rved

.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

New

-Fill

: A c

on

nec

tive

ti

ssu

e p

rese

nte

d d

iffu

se

infla

mm

ato

ry in

filtr

ate.

Art

eco

ll: A

co

nn

ecti

ve fi

bro

us

and

str

iate

d m

usc

ula

r tis

sue

pre

sen

ted

wit

h d

ense

an

d d

iffu

se in

flam

mat

ory

in

filtr

ate.

Liq

uid

Sili

con

e: F

ibri

llar

con

nec

tive

tis

sue

pre

sen

ted

w

ith

diff

use

infla

mm

ato

ry

infil

trat

e.

Salle

s et

al.,

20

08 P

MID

: 18

4540

07

Bra

zil/

Seve

n m

en a

nd

25

wo

men

wit

h a

n a

vera

ge

age

of 4

3.6

yr

32

5 yr

sin

ce

trea

tmen

t PM

MA

N

ose

, pen

is, N

LF, g

lute

us,

mal

ar a

nd

su

bm

alar

re

gio

ns,

abd

om

en,

per

iocu

lar,

fro

nta

l dep

ress

ed s

car,

fro

nta

l reg

ion

an

d

chin

, gla

bel

la, l

ip

No

t re

po

rted

Ti

ssue

nec

rosi

s (n

= 5

); se

vere

g

ran

ulom

a (n

= 1

0); c

hro

nic

in

flam

mat

ory

reac

tion

(n

= 1

0); l

ip s

tiffn

ess,

lym

ph

edem

a, a

nd

nod

ules

(n

= 6

); hy

per

emia

, ed

ema,

an

d

pus

tule

form

atio

n (n

= 1

)

Zie

lke

et a

l.,

2008

PM

ID:

1817

7399

Ger

man

y/Pa

tien

ts w

ith

p

rio

r tre

atm

ents

of

der

mal

fille

rs w

ho

d

evel

op

ed a

reac

tio

n

In o

ne

or m

ore

of t

he

trea

ted

are

as

56 (5

5 w

om

en,

on

e m

an);

eig

ht

pat

ien

ts w

ere

excl

ud

ed

so t

hat

48

rem

ain

ed

for f

urt

her

an

alys

is

No

t re

po

rted

B

iod

egra

dab

le

fille

r, H

A, a

nd

n

on

bio

deg

rad

able

fil

ler,

PMM

A,

po

lyac

ryla

mid

e g

el,

and

po

lyet

hyl

ene

167

trea

ted

are

as in

48

pat

ien

ts

NLF

(n =

67)

, fo

llow

ed

by

the

lips

(n =

27)

, co

rner

s o

f th

e m

ou

th

(n =

27)

, an

d g

lab

ella

(n

= 1

6)

No

t re

po

rted

In

10

pat

ien

ts, 2

4 ar

eas

wer

e tr

eate

d w

ith

HA

. Th

e ar

eas

mo

st o

ften

inje

cted

wer

e th

e n

aso

lab

ial f

old

s (n

= 1

5).

In re

lati

on

to t

he

nu

mb

er

of a

reas

tre

ated

wit

h H

A,

the

mo

st fr

equ

ent

AEs

wer

e sw

ellin

g (7

0.8%

), er

yth

ema

(66.

7%),

and

no

du

le

form

atio

n (6

2.5%

).

In 1

3 ca

ses,

51 a

reas

wer

e in

ject

ed w

ith

po

lyla

ctic

ac

id; t

he

area

s m

ost

o

ften

tre

ated

wer

e th

e n

aso

lab

ial f

old

s (n

= 1

8).

AEs

wer

e n

od

ule

s (6

6.7%

), it

chin

g (2

5.5%

), an

d

lpig

men

tati

on

(17.

6%)

In s

ix p

atie

nts

, 21

area

s w

ere

trea

ted

wit

h P

MM

A, t

he

lip

verm

ilio

n (n

= 8

) bei

ng

th

e ar

ea t

reat

ed m

ost

oft

en. T

he

mo

st fr

equ

entl

y o

bse

rved

A

Es a

fter

PM

MA

inje

ctio

n

wer

e n

od

ule

s (6

6.7%

), er

yth

ema

(33.

3%),

and

sw

ellin

g (1

9.9%

)

J Am AcAd dermAtol


In 1

5 p

atie

nts

, 53

area

s w

ere

trea

ted

wit

h H

EMA

. Th

e ar

eas

mo

st o

ften

tre

ated

w

ere

the

nas

ola

bia

l fo

lds

(n =

22)

. No

du

les

(86.

8%),

eryt

hem

a (5

2.8%

), an

d

pig

men

tati

on

37.

7%)

occ

urr

ed m

ost

(oft

en in

re

lati

on

to t

he

nu

mb

er o

f tr

eate

d a

reas

)..

In fo

ur p

atie

nts

, 18

area

s w

ere

trea

ted

wit

h

po

lyac

ryla

mid

e; t

he

NLF

s (n

= 6

) wer

e tr

eate

d m

ost

o

ften

. In

rela

tio

n to

th

e n

um

ber

of t

reat

ed a

reas

, p

igm

enta

tio

n (3

8.9%

), n

od

ule

s (3

8.9%

), an

d p

ain

(3

8.9%

) wer

e re

po

rted

mo

st

oft

en a

fter

tre

atm

ent

wit

h

po

lyac

ryla

mid

e.

HA

, ery

them

a, s

wel

ling,

an

d

nod

ule

form

atio

n w

ere

the

rele

vant

ad

vers

e ev

ents

w

ith a

med

ian

sev

erit

y g

reat

er th

an 0

. HA

cau

sed

si

gn

ifica

ntly

mor

e se

vere

er

yth

ema

(med

ian

, 1) a

nd

sw

ellin

g (m

edia

n, 2

) th

an

the

oth

er d

egra

dab

le fi

ller

pol

ylac

tic a

cid

[med

ian

fo

r ery

them

a, 0

(p =

0.0

01);

med

ian

for s

wel

ling,

0 (p

=

0.0

02)]

. Pol

ylac

tic a

cid

sh

owed

a m

edia

n g

reat

er

than

0 o

nly

for n

odul

e fo

rmat

ion

(med

ian

, 2).

In

the

non

bio

deg

rad

able

g

roup

, HEM

A c

ause

d m

ore

seve

re n

odul

es (m

edia

n, 3

) th

an P

MM

A [m

edia

n, 2

(p =

0.

03)]

. Nod

ule

form

atio

n in

H

EMA

was

acc

omp

anie

d b

y er

yth

ema

with

a m

edia

n o

f 1.

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D, A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

PM

MA

, po

lym

eth

ylm

eth

acry

late

; PM

ID, P

ub

Med

iden

tific

atio

n n

um

ber

; USA

, Un

ited

Sta

tes;

NLF

, nas

ola

bia

l fo

ld; A

Es,

adve

rse

even

ts; R

CT,

ran

do

miz

ed c

on

tro

lled

tri

al; F

FA, F

acia

l Fo

ld A

sses

smen

t; A

IDS,

acq

uir

ed im

mu

no

defi

cien

cy s

ynd

rom

e; N

/A, n

ot

app

licab

le; H

IV, h

um

an im

mu

no

defi

cien

cy v

iru

s; H

A, h

yalu

ron

ic a

cid

; 3D

, th

ree-

dim

ensi

on

al; H

EMA

, 2-h

ydro

xyet

hyl

met

hac

ryla

te.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Sili

con

e O

il F

iller

sS

yste

mat

ic R

evie

w: N

o. o

f S

tud

ies,

1

Ch

asan

, 200

7 PM

ID:

1809

0770

U

SAN

/AN

/ASi

lico

ne

oil

N/A

N/A

Maj

ori

ty o

f co

mp

licat

ion

s in

volv

ed t

he

chee

ks, N

LFs,

and

gla

bel

la. R

ang

e o

n

com

plic

atio

n o

nse

t is

6

mo

–36

yr. M

ajo

rity

of

com

plic

atio

ns

ob

serv

ed

incl

ud

e g

ran

ulo

mas

, n

od

ula

rity

, mig

rati

on

, an

d

chro

nic

cel

lulit

es.

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f S

tud

ies,

1Jo

nes

et

al.,

2004

PM

ID: 1

5458

523

USA

an

d C

anad

a/Pa

tien

ts

wit

h s

tab

le, w

ell-

con

tro

lled

HIV

77N

/ASi

liko

n 1

000

or

Vit

reSi

l 100

0

(n =

77)

Ch

eeks

for t

reat

men

t o

f fac

ial l

ipo

atro

ph

y 37

6 to

tal i

nje

ctio

n

amo

ng

77

pat

ien

ts

1. M

ean

nu

mb

er o

f wee

ks

nee

ded

to a

chie

ve

com

ple

te c

orr

ecti

on

, firs

t to

la

st in

ject

ion

2. M

ean

nu

mb

er o

f tre

atm

ents

3. M

ean

tota

l vo

lum

e in

ject

ed

(ml)

Bas

ed o

n C

arru

ther

s lip

oat

rop

hy

seve

rity

sca

le

No

AEs

wer

e n

ote

d a

fter

an

y tr

eatm

ent.

AEs

are

defi

ned

as

po

sttr

eatm

ent

pai

n,

eryt

hem

a, o

r ed

ema

last

ing

lo

ng

er t

han

3 d

ays

or

ecch

ymo

sis

last

ing

lon

ger

th

an 2

wk.

The

maj

ori

ty o

f pat

ien

ts

exp

erie

nce

d m

ild to

m

od

erat

e d

isco

mfo

rt

rela

ted

to m

ult

iple

nee

dle

p

un

ctu

res

req

uir

ed fo

r th

e in

ject

ion

tech

niq

ue.

Mo

st p

atie

nts

exp

erie

nce

d

mild

po

sttr

eatm

ent

eryt

hem

a, a

nd

occ

asio

nal

ly

mild

ten

der

nes

s, w

hic

h in

al

l cas

es re

solv

ed in

less

th

an 3

day

s.

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

4Ja

cin

to, 2

005

PMID

: 16

4166

37

Phili

pp

ines

/Pat

ien

ts

un

der

go

ing

so

ft-t

issu

e au

gm

enta

tio

n

206

case

s N

/A (1

91

case

s)

N/A

Silic

on

e o

il, 0

.5–4

.6 m

l In

trad

erm

al in

ject

ions

for a

cne

and

pos

tvar

icel

la s

cars

Dee

p d

erm

al in

ject

ion

s fo

r nas

ola

bia

l gro

oves

, g

lab

ella

r fro

wn

lin

es,

infr

amal

ar c

reas

es a

nd

d

epre

ssio

ns,

mar

ion

ette

lin

es, a

nd

sle

ep li

nes

Clin

ical

im

pro

vem

ent

gra

ded

as

exce

llen

t, g

oo

d,

fair,

or p

oo

r

Five

had

ery

them

ato

us

pap

ule

s.

J Am AcAd dermAtol


Para

da

et a

l., 2

005

PMID

: 162

7614

9 B

razi

l11

No

t re

po

rted

Res

tyla

ne

(HA

), M

etaC

rill

(po

lym

eth

ylm

eth

acry

late

), A

qu

amid

(po

lyac

ryla

mid

e),

New

-Fill

(po

lyla

ctic

ac

id),

Art

eco

ll (p

oly

met

hyl

met

hac

ryla

te

susp

end

ed in

a c

olla

gen

so

luti

on

)

Bio

psy

sp

ecim

ens

fixed

in

10%

form

alin

R

esty

lan

e: A

n in

flam

mat

ory

p

roce

ss o

ccu

rred

on

th

e d

eep

reti

cula

r der

mis

, h

ypo

der

mis

, an

d a

t th

e le

vel

of t

he

der

mal

mu

scu

latu

re.

Peri

adn

exal

an

d p

eriv

ascu

lar

lym

ph

om

on

on

ucl

ear

infil

trat

es w

ere

ob

serv

ed

in t

he

sup

erfic

ial a

nd

dee

p

der

mis

, in

ad

dit

ion

to

nu

mer

ou

s eo

sin

op

hils

.

Aq

uam

id: I

nfla

mm

ato

ry

infil

trat

es w

ere

ob

serv

ed o

n

the

dee

p re

ticu

lar d

erm

is,

hyp

od

erm

is, a

nd

der

mal

m

usc

ula

ture

.M

etaC

rill:

A fo

cal o

r diff

use

in

flam

mat

ory

infil

trat

e at

th

e re

ticu

lar d

erm

is a

nd

h

ypo

der

mis

was

ob

serv

ed.

New

-Fill

: A c

on

nec

tive

ti

ssu

e p

rese

nte

d d

iffu

se

infla

mm

ato

ry in

filtr

ate.

Art

eco

ll: A

co

nn

ecti

ve fi

bro

us

and

str

iate

d m

usc

ula

r tis

sue

pre

sen

ted

wit

h d

ense

an

d d

iffu

se in

flam

mat

ory

in

filtr

ate.

Liq

uid

Sili

con

e: F

ibri

llar

con

nec

tive

tis

sue

pre

sen

ted

w

ith

diff

use

infla

mm

ato

ry

infil

trat

e.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/

po

pu

lati

on

ty

pe

Sam

ple

si

ze

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

4

Pove

da

et a

l., 2

006

PMID

: 163

8828

5 Sp

ain

/55-

yr-o

ld

wo

man

,72

-yr-

old

wo

man

,

70-y

r-o

ld w

om

an,

54-y

r-o

ld w

om

an,

43-y

r-o

ld w

om

an

51

mo

Bo

tulin

um

toxi

n t

ype

A (B

oto

x)

(n =

1)

Co

llag

en (n

= 1

)

Dim

eth

ylp

oly

silo

xan

e (s

ilico

ne)

(n

= 3

)

Inje

ctio

ns

into

th

e lo

wer

an

d u

pp

er li

ps,

nas

og

enia

n a

rea,

faci

al

area

, ch

eeks

, ch

in, a

nd

b

ucc

al m

uco

sa

Dis

cret

e tr

abec

ula

tio

n

of t

he

man

dib

ula

r an

d s

ub

man

dib

ula

r su

bcu

tan

eou

s fa

t re

late

d

to in

flam

mat

ion

ch

ang

es;

inte

nse

infla

mm

ato

ry

pro

cess

es a

ffec

tin

g a

lmo

st

the

enti

re s

ub

cuta

neo

us

cellu

lar t

issu

e co

veri

ng

th

e m

axill

ae a

nd

th

e flo

or

of t

he

mo

uth

an

d a

larg

e p

art

of t

he

bu

ccal

mu

cosa

; g

ener

aliz

ed, b

ilate

ral,

faci

al

tum

efac

tio

n; s

wel

ling

of t

he

lips

and

ch

eeks

Req

uen

a et

al.,

200

1 PM

ID: 1

1391

099

Spai

n/5

2-yr

-old

m

an, 4

2-yr

-old

w

om

an, t

wo

38

-yr-

old

wo

men

46–

14 m

oA

rtec

oll

(n =

1)

Der

mal

ive

(n =

1)

Silic

on

e (n

= 2

)

Art

eco

ll: N

aso

lab

ial a

nd

fo

reh

ead

fold

sD

erm

aliv

e: F

ore

hea

d a

nd

p

erio

cula

r rid

ges

Silic

on

e: N

LFs,

chee

ks

Art

eco

ll: E

ryth

emat

ou

s, ri

bb

ed,

pal

pab

le in

du

rati

on

s o

f bo

th

nas

ola

bia

l an

d fo

reh

ead

fo

lds

Der

mal

ive:

Ery

them

ato

us

pal

pab

le in

du

rati

on

s o

n

fore

hea

d

Silic

on

e: E

ryth

emat

ou

s p

alp

able

ind

ura

tio

ns

of b

oth

n

aso

lab

ial f

old

s, p

alp

able

in

du

rati

on

s o

n b

oth

ch

eeks

w

ith

mild

ery

them

a

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D, A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

PM

ID, P

ub

Med

iden

tific

atio

n n

um

ber

; USA

, Un

ited

Sta

tes;

N/A

, no

t ap

plic

able

; NLF

s, n

aso

lab

ial f

old

s; A

Es, a

dve

rse

even

ts; H

IV, h

um

an im

mu

no

defi

cien

cy v

iru

s.

J Am AcAd dermAtol


Oth

er F

iller

sS

yste

mat

ic R

evie

w: N

o. o

f S

tud

ies,

1

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

Size

F

oll

ow

-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

Ko

sow

ski e

t al

.,

2009

PM

ID: 1

9483

584

USA

/Pat

ien

ts w

ho

re

ceiv

ed e

lect

ive

faci

al

cosm

etic

pro

ced

ure

s (e

.g.,

inje

ctab

le fi

llers

, im

pla

nts

, bo

tulin

um

to

xin

tre

atm

ent)

to

imp

rove

faci

al

app

eara

nce

Nin

e q

ues

tio

n-

nai

res

to

asse

ss fa

cial

ap

pea

ran

ce

N/A

Inje

ctab

le

fille

rs

Imp

lan

ts

Bo

tulin

um

to

xin

No

t re

po

rted

1. R

hin

op

last

y O

utc

om

es

Eval

uat

ion

2. G

lasg

ow

Ben

efit

Inve

nto

ry,

Faci

al A

pp

eara

nce

So

rtin

g T

est

3. F

acia

l Lin

es T

reat

men

t Sa

tisf

acti

on

Qu

esti

on

nai

re

4. S

kin

Rej

uve

nat

ion

Ou

tco

mes

Ev

alu

atio

n

5. F

acia

l Lin

es O

utc

om

es

Qu

esti

on

nai

re

6. F

acel

ift O

utc

om

es E

valu

atio

n

7. R

hin

op

last

y O

utc

om

es

Eval

uat

ion

8. D

erri

ford

Ap

pea

ran

ce S

cale

59

N/A



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

Ran

do

miz

ed C

on

tro

lled

Tri

al: N

o. o

f S

tud

ies,

1

Scla

fan

i et

al.,

2002

PM

ID:

1243

7432

U

SA/P

atie

nts

wit

h a

ge-

re

late

d c

han

ges

in t

he

size

an

d c

on

tou

r of

the

lip

44 (4

4)3,

6, 9

, 12

mo

C

ymet

ra

(n =

19)

Zyp

last

(n

= 2

5)

Inje

ctio

n to

th

e u

pp

er li

p

bet

wee

n t

he

orb

icu

lari

s o

ris

mu

scle

an

d t

he

over

lyin

g

mu

cocu

tan

eou

s ju

nct

ion

of

the

up

per

lip

1. C

han

ges

in t

he

nas

ola

bia

l an

gle

2. P

erce

nta

ge

of t

he

tota

l lip

acc

ou

nte

d

for b

y th

e ex

po

sed

re

d li

p in

th

e m

idlin

e an

d o

n t

he

late

ral v

iew

3. V

isib

le re

d u

pp

er

and

low

er li

p

surf

ace

area

s

4. A

nte

rio

r pro

ject

ion

o

f th

e u

pp

er a

nd

lo

wer

lip

s

No

sig

nifi

can

t lo

cal o

r sys

tem

ic

com

plic

atio

ns

Un

con

tro

lled

Clin

ical

Tri

al: N

o. o

f S

tud

ies,

7

Bja

rnsh

olt

et

al.,

2009

PM

ID: 1

9709

133

Den

mar

k/Pa

tien

ts w

ith

ad

vers

e re

acti

on

s af

ter i

nje

ctio

n o

f p

oly

acry

lam

ide

gel

814

day

s– 2

yr s

ince

in

ject

ion

A

qu

amid

(n =

1)

Inte

rfal

l (n

= 1

) Li

p (n

= 3

) Pen

is (n

= 1

) Bre

ast

(n =

1) T

ear t

rou

gh

(n =

1)

NLF

(n =

1) C

hee

k (n

= 1

)

Pres

ence

of b

acte

ria

in

bio

psy

sp

ecim

en o

f le

sio

ns

fro

m a

dve

rse

reac

tio

n to

der

mal

fille

r

Lesi

on

s fr

om

der

mal

fil

ler

de

Cas

sia

et a

l., 2

003

PMID

: 146

1299

4 Sw

eden

/Pat

ien

ts

un

der

go

ing

faci

al

aug

men

tati

on

592–

16 m

o (9

mo

av

erag

e)A

qu

amid

Inje

ctio

n s

ub

cuta

neo

usl

y b

y re

tro

gra

de

linea

r tra

cin

g

inje

ctio

n te

chn

iqu

e fo

r lip

au

gm

enta

tio

n, c

hee

kbo

ne

enla

rgem

ent,

dee

p N

LFs,

gla

bel

la, c

hin

Pati

ent

sati

sfac

tio

nSl

igh

t re

dn

ess

and

te

mp

ora

ry s

wel

ling

im

med

iate

ly a

fter

in

ject

ion

su

bsi

ded

w

ith

in 3

6 h

r.

J Am AcAd dermAtol


Han

et

al.,

2006

PM

ID:

1650

8353

K

ore

a/Pa

tien

ts

un

der

go

ing

au

gm

enta

tio

n

rhin

op

last

y

11 (6

)12

mo

Cu

ltu

red

hu

man

fib

rob

last

s su

spen

ded

in

Res

tyla

ne,

0.6

–1.0

ml

Inje

ctio

n in

to t

he

sub

cuta

neo

us

laye

r of t

he

nas

al d

ors

um

1. A

pp

eara

nce

of

reco

nst

ruct

ed

no

ses,

deg

ree

and

ti

me

of r

eso

rpti

on

, an

d o

ccu

rren

ce o

f co

mp

licat

ion

s

2. P

atie

nt

sati

sfac

tio

n

usi

ng

a V

AS

form

Mild

deg

ree

of d

ors

al

dev

iati

on

in o

ne

pat

ien

t

Trea

cy e

t al

., 20

06 P

MID

: 16

7926

45

USA

/HIV

pat

ien

ts w

ith

fa

cial

lip

od

ystr

op

hy

11 (1

1)3

and

18

mo

B

io-A

lcam

id

po

lyac

ryla

mid

e g

el,

15.0

–30.

0 cm

3

Poly

acry

lam

ide

gel

inje

cted

in

to t

he

bu

ccal

, mal

ar,

and

tem

po

ral a

reas

o

f th

e fa

ce, s

up

erfic

ial

to t

he

sup

erfic

ial

mu

scu

loap

on

euro

tic

syst

em

1. Q

ual

ity

of l

ife u

sin

g

a m

od

ified

Bec

k d

epre

ssio

n s

cale

2. C

linic

al im

pro

vem

ent

at

3 a

nd

18

mo

No

ne

von

Bu

elo

w e

t al

., 20

05

PMID

: 161

6310

8 D

enm

ark,

Ger

man

y, It

aly,

Th

e N

eth

erla

nd

s, Sp

ain

, Sw

eden

/Pa

tien

ts u

nd

erg

oin

g

faci

al a

ug

men

tati

on

an

d e

nh

ance

men

t o

f fa

cial

co

nto

urs

cau

sed

b

y ag

ing,

acn

e, t

rau

ma,

o

r su

rger

y

251

(228

)7,

28

day

s; 3

, 6, 1

2 m

o

Aq

uam

id, 0

.2–1

2.0

ml

Gel

ad

min

iste

red

th

rou

gh

th

e su

bcu

tan

eou

s ti

ssu

e u

sin

g

a th

in n

eed

le. I

nje

ctio

n

star

ts a

s th

e n

eed

le is

w

ith

dra

wn

fro

m t

he

nas

ola

bia

l an

d g

lab

ella

fo

lds,

dep

ress

ed c

orn

ers

of t

he

mo

uth

, per

iora

l w

rin

kles

, lip

, ch

in, c

hee

ks,

no

se, a

nd

ver

mill

ion

b

ord

er.

1. A

esth

etic

ou

tco

me

as e

valu

ated

by

the

ph

ysic

ian

at

12 m

o

2. A

esth

etic

ou

tco

me

as e

valu

ated

by

the

pat

ien

t at

12

mo

Neu

tro

pen

ia in

on

e p

atie

nt

Mo

st c

om

mo

n A

Es

incl

ud

ed t

ran

sien

t sw

ellin

g, h

emat

om

a,

red

nes

s, p

ain

, or

itch

ing

(37

case

s).

von

Bu

elo

w e

t al

., 20

06

PMID

: 169

3654

8 G

erm

any/

Pati

ents

wit

h

mea

n a

ge

of 4

8 yr

, 8%

m

ale

251

(101

)24

mo

Aq

uam

idN

aso

lab

ial a

nd

gla

bel

la fo

lds,

dep

ress

ed c

orn

ers

of

the

mo

uth

, an

d p

erio

ral

wri

nkl

es F

acia

l co

nto

uri

ng,

lip

au

gm

enta

tio

n P

atie

nt

sati

sfac

tio

n c

lass

ified

as

very

sat

isfie

d, s

atis

fied,

or

no

t sa

tisfi

ed.

Effic

acy

mea

sure

d b

y ae

sth

etic

resu

lts

to b

e ve

ry g

oo

d, g

oo

d, b

ad,

or v

ery

bad

69 A

Es re

po

rted

in

the

first

yea

r, w

ith

37

cas

es h

avin

g a

p

oss

ible

to a

lmo

st

cert

ain

rela

tio

nsh

ip

to t

he

gel

inje

ctio

n.

28 t

ran

sien

t lo

cal

tiss

ue

reac

tio

ns

Oth

er o

bse

rvat

ion

s in

clu

de

faci

al

pim

ple

s, h

erp

es,

neu

tro

pen

ia,

eosi

no

ph

ilia,

m

on

ocy

tosi

s, an

d

an.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

elev

atio

n o

f cir

cula

tin

g

imm

un

og

lob

ulin

On

e p

atie

nt

dev

elo

ped

a

hem

ato

ma

at 2

8 d

ays

afte

r tre

atm

ent

and

imp

rove

d o

ver

the

nex

t 2

wk.

At

the

2-yr

follo

w-u

p,

pat

ien

t re

po

rted

an

into

lera

nce

to

sun

ligh

t ex

po

sure

at

aff

ecte

d s

ites

th

at

reve

aled

a fl

uid

-fil

led

cys

t.

An

oth

er p

atie

nt

rep

ort

ed a

tr

ansi

ent

per

iod

of

efflo

resc

ent

eyel

ids

last

ing

ove

r 2 w

k th

at o

ccu

rred

at

5 m

o a

fter

tre

atm

ent

Wo

lter

s et

al.,

200

9 PM

ID: 1

9207

323

Ger

man

y/G

ener

al

po

pu

lati

on

251

(81)

36–4

8 m

oC

ross

-lin

ked

p

oly

acry

lam

ide

hyd

rog

el

Vari

ou

s fa

cial

co

nto

uri

ng

lo

cati

on

s, n

ot

exp

licit

ly

rep

ort

ed

1. P

atie

nt

sati

sfac

tio

n

2. In

vest

igat

or a

sses

smen

t at

36/

48 m

o

Two

(2.5

%) o

f nin

e (1

1%) A

Es re

po

rted

d

uri

ng

th

e st

ud

y p

erio

d w

ere

con

sid

ered

to

hav

e a

po

ssib

le

rela

tio

nsh

ip to

th

e fil

ler i

nje

ctio

n.

Gra

nu

lom

a fo

rmat

ion

w

as n

ot

det

ecte

d a

t an

y o

f th

e fo

llow

-up

vi

sits

.

J Am AcAd dermAtol


Co

ho

rt S

tud

y: N

o. o

f S

tud

ies,

4H

on

ig, 2

008

PMID

: 18

6507

37

Ger

man

y/N

on

rela

ted

H

IV-s

ero

po

siti

ve

pat

ien

ts w

ith

fa

cial

LA

9M

edia

n,

2 yr

B

io-A

lcam

id,

7–25

ml i

n

chee

k 1–

3 m

l in

NLF

1–2

ml

in li

p li

ne

NLF

, ch

eek,

lip

lin

e1.

Lev

el o

f sat

isfa

ctio

n w

ith

su

rgic

al o

utc

om

eN

ot

rep

ort

ed

Kal

anta

r-H

orm

ozi

et a

l., 2

008

PM:1

9083

518

Iran

/Pat

ien

ts w

ith

a

his

tory

of P

AA

G

inje

ctio

ns

600

2–5

yrPA

AG

542

in v

ario

us

faci

al

loca

tio

ns

Ove

rall

rate

of c

om

plic

atio

n: 7

.7%

. 85%

occ

urr

ed

<1

yr a

fter

inje

ctio

n. I

n t

wo

pat

ien

ts, a

n a

bsc

ess

app

eare

d in

the

inje

ctio

n s

ite

afte

r mo

re th

an 3

yr.

Ab

sces

s fo

rmat

ion

(5.9

%) D

isp

lace

men

t o

f gel

(5.3

%)

Neg

red

o e

t al

., 20

06 P

MID

: 17

1921

48

Spai

n/H

IV-i

nfe

cted

p

atie

nts

p

rese

nti

ng

wit

h

anti

retr

ovir

al-

asso

ciat

ed fa

cial

lip

oat

rop

hy

for

mo

re t

han

6 m

o

138

(eig

ht

rece

ived

fa

t, 25

rece

ived

PL

LA, a

nd

10

5 re

ceiv

ed

po

lyac

ryla

mid

e g

el)

96 w

kA

nal

og

ou

s fa

t o

bta

ined

by

lipo

suct

ion

, 50

ml

PLLA

, 3–1

4 m

l

Poly

acry

lam

ide

gel

, 4–1

8 m

l

NLF

sLe

vel o

f fac

ial l

ipo

atro

ph

y fr

om

ph

oto

gra

ph

ic a

nd

se

lf- a

sses

smen

t

All

pat

ien

ts c

om

pla

ined

of p

ain

at

the

infil

trat

ion

si

te d

uri

ng

th

e in

terv

enti

on

, an

d fa

cial

ed

ema

for 2

–3 d

ays,

wh

ich

was

alw

ays

min

imal

an

d

tran

sien

t. Ec

chym

ose

s w

ere

ob

serv

ed in

14%

o

f pat

ien

ts, m

ost

cas

es (1

3%) b

ein

g in

th

e p

oly

acry

lam

ide

gro

up

. Sev

en o

f 21

wo

men

(33%

) in

clu

ded

in t

he

po

lyac

ryla

mid

e g

rou

p m

anife

sted

ec

chym

ose

s. A

ll ca

ses

reso

lved

sp

on

tan

eou

sly

wit

hin

3–5

day

s. Tw

o p

atie

nts

fro

m t

he

PLLA

g

rou

p (1

.4%

of t

he

tota

l nu

mb

er o

f pat

ien

ts

incl

ud

ed) p

rese

nte

d p

alp

able

su

bcu

tan

eou

s m

icro

no

du

les

in t

he

mal

ar a

rea,

an

d t

wo

su

bje

cts

fro

m t

he

po

lyac

ryla

mid

e g

rou

p (1

.4%

o

f th

e to

tal)

dev

elo

ped

a s

up

erfic

ial c

uta

neo

us

infe

ctio

n, w

hic

h w

as e

asily

co

ntr

olle

d w

ith

an

o

ral a

nti

bio

tic

(th

e sp

ecifi

c ty

pe

of b

acte

ria

was

no

t id

enti

fied

). O

nly

tw

o p

atie

nts

req

uir

ed

wit

hd

raw

al o

f th

e su

bst

ance

aft

er p

oly

acry

lam

ide

infil

trat

ion

s b

ecau

se o

f a h

yper

corr

ecti

on

or

exce

ss o

f su

bst

ance

in t

he

mal

ar a

rea

(on

e m

an

and

on

e w

om

an).

Red

a-La

ri, 2

008

PMID

: 190

8351

7Ku

wai

t/Pa

tien

ts

trea

ted

wit

h P

AH

G

for s

oft

- tis

sue

aug

men

tati

on

of

the

mal

ar a

rea

2136

3 m

o–6

yr

PAH

G, 1

.5–5

ml

Peri

orb

ital

(tea

r tr

ou

gh

, up

per

lid

), te

mp

le, l

ater

al

face

(go

nia

l an

gle

ar

ea),

bu

ccal

, mal

ar,

nas

al, n

aso

lab

ial,

lip a

nd

ch

in, o

r an

y co

mb

inat

ion

of t

he

abov

e

1. P

atie

nt

sati

sfac

tio

nO

ccu

rred

in 1

11 p

atie

nts

(8.4

%)

Lum

ps

(n =

56)

Gel

dis

pla

cem

ent

(n =

43)

Pro

lon

ged

p

ain

(n =

5) I

nfe

ctio

n (n

= 3

)



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

F

oll

ow

-up

Tre

atm

ent

Inje

ctio

n

des

crip

tio

nO

utc

om

e

mea

sure

sA

dve

rse

even

ts

Cro

ss-S

ecti

on

al S

tud

y: N

o. o

f S

tud

ies,

1

Zap

pi e

t al

., PM

ID: 1

8086

057

USA

/Pat

ien

ts t

reat

ed w

ith

LIS

for

dep

ress

ed s

cars

on

th

e fa

ce

35 s

amp

les

(25

pat

ien

ts)

1–23

yr

LIS,

0.0

5–0.

2 m

l sp

ecim

en

No

t re

po

rted

1. L

igh

t m

icro

sco

py

ex

amin

atio

n o

f ski

n

bio

psy

Det

ecte

d s

ilico

ne

faile

d to

el

icit

an

y si

gn

ifica

nt

adve

rse

reac

tio

n.

Cas

e S

erie

s/R

epo

rt: N

o. o

f S

tud

ies,

16

Am

in e

t al

., 20

04

PMID

: 15

6068

26

Fran

ce/6

4-yr

-old

fem

ale

U.S

. cit

izen

1

5 m

oPA

AG

Der

mal

inje

ctio

ns

of

po

lyac

ryla

mid

e g

el in

ch

eeks

Eryt

hem

ato

us

no

du

les

at in

ject

ion

sit

e

Ap

te e

t al

., 20

03

PMID

: 12

9727

73

USA

/48-

yr-o

ld w

om

an1

2 m

oC

ymet

ra (h

um

an c

adav

er

colla

gen

) Fo

reh

ead

The

pat

ien

t re

po

rted

nau

sea

and

d

iap

ho

resi

s im

med

iate

ly fo

llow

ing

th

e p

roce

du

re. S

he

then

no

tice

d

on

e-si

ded

per

iocu

lar p

ain

, an

d

blu

rred

vis

ion

in h

er le

ft e

ye. T

wo

m

on

ths

late

r, p

atie

nt

had

lig

ht

per

cep

tio

n v

isio

n w

ith

a m

arke

d

affe

ren

t p

up

illar

y d

efec

t an

d la

rge

area

s o

f ret

inal

pig

men

t ep

ith

eliu

m

atro

ph

y an

d p

igm

ent

dis

per

sio

n.

Ch

eng

et

al.,

2006

PM

ID:

1654

7628

Ch

ina/

Wo

men

ag

ed

24–4

5 yr

15

1–7

yrPA

AG

Face

, bre

asts

, leg

sB

od

y co

nto

ur d

isfig

ure

men

t an

d

imp

lan

t d

isp

lace

men

t. Th

e g

el

lum

ps

cou

ld b

e m

oved

un

der

p

ress

ure

pal

pat

ion

.D

esca

mp

s et

al

., 20

08

PMID

: 18

4460

29

Fran

ce/P

atie

nts

wit

h

chro

nic

hep

atit

is C

tr

eate

d w

ith

inte

rfer

on

al

fa

2C

ase

1: 5

yr a

fter

tr

eatm

ent

Cas

e 2:

2

yr a

fter

tr

eatm

ent

Cas

e 1:

Un

kno

wn

per

man

ent

der

mal

fille

r C

ase

2: H

yalu

ron

ic

acid

Cas

e 1:

Mes

ola

bia

l an

d

nas

ola

bia

l fo

lds

Cas

e 2:

Per

ibu

ccal

an

d

lion’

s w

rin

kles

No

t re

po

rted

Cas

e 1:

Sar

coid

al g

ran

ulo

mas

pre

sen

t in

no

du

les

fou

nd

in t

he

leg

s, ed

ema

in t

he

face

wit

h in

filtr

ated

mas

ses

in t

he

mes

ola

bia

l an

d n

aso

lab

ial

fold

s p

rese

nt

wit

h g

ran

ulo

mas

w

ith

vac

uo

late

d m

acro

ph

ages

, p

ulm

on

ary

fun

ctio

n te

sts

reve

al

dec

reas

e in

th

e d

iffu

sio

n c

apac

ity

of

carb

on

mo

nox

ide

(58%

of n

orm

al

valu

e) a

nd

tu

ber

culin

an

erg

y w

as

ob

serv

ed.

J Am AcAd dermAtol


Cas

e 2:

Ed

ema

and

infil

trat

ed n

od

ule

s w

ith

pu

rpu

ra in

th

e lip

s an

d t

he

inje

cted

are

as; b

iop

sy c

on

firm

ed

fore

ign

bo

dy

gra

nu

lom

a; in

terf

ero

n

and

rib

avir

in w

ere

dis

con

tin

ued

b

ut

late

r cir

rho

sis

was

dia

gn

ose

d

and

inte

rfer

on

an

d r

ibav

irin

wer

e g

iven

ag

ain

; pat

ien

t d

evel

op

ed

sicc

a sy

mp

tom

s an

d e

dem

a an

d p

urp

uri

c in

filtr

ated

lesi

on

s fla

red

up

ag

ain

; bio

psy

was

ty

pic

al o

f sar

coid

osi

s; c

hes

t C

T sc

an d

emo

nst

rate

d p

ulm

on

ary

sarc

oid

osi

s w

ith

lym

ph

aden

op

ath

y an

d m

icro

no

du

les

wer

e co

nfir

med

b

y g

alliu

m.

Go

ldm

an,

2009

PM

ID:

1920

7334

USA

, Ita

ly/4

6-yr

-old

w

om

an1

(1)

2 d

ays

afte

r fin

al

trea

tmen

t th

rou

gh

10

mo

aft

er fi

nal

tr

eatm

ent

Aq

uam

id (p

oly

acry

lam

ide

gel

)

3.0

ml i

n 2

002,

0.7

ml i

n A

ug

ust

o

f 200

4, 1

ml i

n A

ug

ust

of

2005

, 1 m

l in

Feb

ruar

y o

f 20

05, 0

.8 m

l in

Oct

ob

er o

f 20

07, 1

ml i

n N

ovem

ber

of

2007

Up

per

an

d lo

wer

lip

s d

uri

ng

tw

o s

epar

ate

sess

ion

s, 2

wk

apar

t in

20

02; N

LF in

Au

gu

st o

f 20

04; N

LF a

nd

up

per

lip

in A

ug

ust

of 2

005;

u

pp

er a

nd

low

er li

p

and

NLF

in F

ebru

ary

of

2005

; lip

s in

Oct

ob

er

of 2

007;

lip

s in

N

ovem

ber

of 2

007

No

t re

po

rted

Swel

ling

of t

he

rig

ht

up

per

lip

th

at

app

eare

d a

s a

firm

, par

tial

ly m

ob

ile,

no

nte

nd

er, s

ub

cuta

neo

us,

har

d

no

du

le w

ith

ou

t er

yth

ema

2 m

o a

fter

fin

al t

reat

men

t, p

atie

nt

pre

sen

ted

wit

h fr

eely

mo

bile

, n

on

ten

der

su

bcu

tan

eou

s n

od

ule

15

mm

in d

iam

eter

on

th

e le

ft

mid

bu

ccal

mu

cosa

.

Gri

mal

di e

t al

., 20

08

PMID

: 18

6507

38

Ital

y/50

-yr-

old

wo

man

w

ith

Ro

mb

erg

sy

nd

rom

e o

f th

e le

ft

face

of 2

0-yr

du

rati

on

1N

ot

rep

ort

edPo

lyg

lact

ic a

cid

an

d fa

t fr

om

th

e ab

do

min

al a

rea

Of f

at: 1

5 m

l in

th

e ri

gh

t zy

go

mat

ic re

gio

n

25 m

l in

left

ch

eek

10 m

l in

bu

ccal

rim

e

5 m

l in

th

e le

ft u

pp

er

eyel

id

15 m

l in

th

e le

ft te

mp

ora

l ar

ea

3 m

l in

su

pra

orb

ital

are

a

No

t re

po

rted

No

ne

rep

ort

ed



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

Jham

et

al.,

PMID

: 19

1386

00

Vari

ou

s/G

ener

al

po

pu

lati

on

56Va

rio

us

Up

per

/lo

wer

lip

, NLF

, ch

eek

No

t re

po

rted

Clin

ical

pre

sen

tati

on

: Sin

gle

no

du

le,

diff

use

sw

ellin

g, m

ult

iple

no

du

les,

mas

s, o

ther

Trea

tmen

ts: E

xcis

ion

al b

iop

sy, s

tero

ids

(sys

tem

ic a

nd

intr

ales

ion

al),

anti

bio

tics

, no

nst

ero

idal

an

tiin

flam

mat

ory

dru

gs,

uri

cosu

ric

agen

t, im

mu

no

reg

ula

tor

Kan

chw

ala

et a

l., 2

005

PMID

: 15

9857

88

USA

/Pat

ien

ts u

nd

erg

oin

g

faci

al a

ug

men

tati

on

976

3, 6

, 9, 1

2

mo

Au

tolo

go

us

fat

(n =

697

)

Hyl

afo

rm (n

= 5

2)

Res

tyla

ne

(n =

86)

Rad

iess

e (n

= 1

41)

Nas

ola

bia

l fo

lds,

lips,

gla

bel

la

1. T

ype

of p

rod

uct

u

sed

2. A

nat

om

ical

re

gio

n in

ject

ed

3. In

fect

ion

rate

4. T

ou

ch-u

p/

revi

sio

n ra

te a

nd

ov

eral

l lo

ng

evit

y

No

t re

po

rted

Kar

agoz

og

lu

et a

l., 2

008

PMID

: 18

3132

68

The

Net

her

lan

ds/

39-y

r-o

ld w

om

an re

ferr

ed

by

her

den

tist

bec

ause

o

f a s

mal

l mo

bile

su

bm

uco

sal s

wel

ling

in

th

e le

ft c

hee

k

1Pr

esen

ted

3

yr s

ince

tr

eatm

ent;

follo

w-u

p o

f 6

mo

aft

er

pre

sen

tati

on

Aq

uam

id (p

oly

acry

lam

ide

gel

) N

LFN

ot

rep

ort

edA

fter

per

form

ing

bio

psy

of t

he

cyst

, th

e h

isto

pat

ho

log

ic e

xam

inat

ion

re

po

rted

th

at t

he

tiss

ue

mo

st

likel

y re

pre

sen

ted

a p

art

of a

m

uco

us

cyst

, bu

t th

e p

oss

ibili

ty o

f m

uco

epid

erm

oid

car

cin

om

a w

as

also

co

nsi

der

ed.

His

top

ath

olo

gic

an

alys

is o

f bo

th

no

du

les

reve

aled

sal

ivar

y g

lan

d t

issu

e w

ith

a h

isto

cyti

c in

flam

mat

ory

infil

trat

e co

nta

inin

g

nu

mer

ou

s fo

reig

n b

od

y g

ian

t ce

lls t

hat

wer

e lin

ing

bir

efri

ng

ent

mat

eria

l.

J Am AcAd dermAtol


Kaw

amu

ra e

t al

., 20

06

PMID

: 16

5457

11

Bra

zil/

61-y

r-o

ld w

hit

e w

om

an1

8–14

mo

Sin

gle

do

se o

f Aq

uam

id (2

.5%

p

oly

acry

lam

ide)

Sin

gle

do

se o

f Aq

uam

id

inje

cted

into

th

e N

LFFi

bro

us

no

du

les

in b

ucc

al m

uco

sa

cau

sed

by

fore

ign

bo

dy

reac

tio

n

Lah

iri e

t al

., 20

07

PMID

: 17

4850

56

UK

/18

men

, 16

wo

men

, ag

ed 2

1–59

yr

121.

5–11

0 m

l Bio

-Alc

amid

(s

ynth

etic

po

lym

eric

p

oly

acry

lam

ide,

en

clo

sed

w

ith

co

llag

en)

Inje

ctio

ns

for f

acia

l an

d

ches

t w

all d

efo

rmit

ies

Pati

ent

sati

sfac

tio

n

wit

h p

roce

du

re

and

resu

lts

On

e H

IV p

atie

nt

dev

elo

ped

an

in

fect

ion

on

th

e ri

gh

t te

mp

ora

l ar

ea t

hat

resu

lted

in a

sm

all a

rea

of

skin

bre

akd

ow

n a

nd

sp

on

tan

eou

s d

isch

arg

e o

f th

e in

ject

ed m

ater

ial.

No

ne;

200

8 PM

ID:

1845

1755

USA

/Hea

lth

y w

om

en3

Cas

e 1,

10

day

s;

Cas

e 2,

13

day

s; C

ase

3,

14 d

ays

Cas

e 1:

Un

kno

wn

for fi

rst

trea

tmen

t; d

erm

al s

ilico

ne

for s

eco

nd

tre

atm

ent

Cas

e 2:

Sili

con

e d

erm

al fi

ller,

500

ml e

ach

bu

tto

ck in

firs

t tr

eatm

ent

and

th

en 4

00 m

l in

sec

on

d t

reat

men

t

Cas

e 3:

Un

kno

wn

so

ft- t

issu

e fil

ler

Cas

e 1:

Bu

tto

cks

Cas

e 2:

Bu

tto

cks

Cas

e 3:

Bu

tto

cks

No

t re

po

rted

Cas

e 1:

Hea

dac

he

and

vo

mit

ing,

pu

rple

u

rin

e w

ith

in 3

0 m

inu

tes

of r

ecei

vin

g

inje

ctio

n o

f der

mal

sili

con

e in

th

e b

utt

ock

s; fo

un

d to

be

in a

cute

ren

al

failu

re.

Cas

e 2:

Wit

hin

1 h

r of s

eco

nd

tr

eatm

ent,

exp

erie

nce

d h

ead

ach

e an

d n

ause

a an

d b

urg

un

dy

uri

ne;

fo

un

d to

hav

e ac

ute

ren

al fa

ilure

; b

iop

sy la

ter r

evea

led

sev

ere

acu

te t

ub

ula

r nec

rosi

s w

ith

cas

e fo

rmat

ion

.

Cas

e 3:

Dev

elo

ped

ab

do

min

al p

ain

1

hr a

fter

tre

atm

ent;

fou

nd

to h

ave

seru

m c

reat

ine

leve

l of 1

1 m

g/

dl;

ren

al b

iop

sy la

ter f

ou

nd

acu

te

inte

rsti

tial

nep

hri

tis

wit

h s

ub

stat

ion

n

um

ber

s o

f eo

sin

op

hils

.



pp

end

ix B

. Co

nt’d

Stu

dy

Co

un

try/p

op

ula

tio

n

typ

e Sa

mp

le

size

Fo

llo

w-u

pT

reat

men

tIn

ject

ion

d

escr

ipti

on

Ou

tco

me

m

easu

res

Ad

vers

e ev

ents

Para

da

et

al.,

2005

PM

ID:

1627

6149

Bra

zil

11N

ot

rep

ort

edR

esty

lan

e (h

yalu

ron

ic

acid

), M

etaC

rill

(po

lym

eth

ylm

eth

acry

late

), A

qu

amid

(po

lyac

ryla

mid

e),

New

-Fill

(PLL

A),

Art

eco

ll (p

oly

met

hyl

met

hac

ryla

te

susp

end

ed in

a c

olla

gen

so

luti

on

).

Bio

psy

sp

ecim

ens

fixed

in

10%

form

alin

R

esty

lan

e: A

n in

flam

mat

ory

pro

cess

o

ccu

rred

on

th

e d

eep

reti

cula

r d

erm

is, h

ypo

der

mis

, an

d a

t th

e le

vel o

f th

e d

erm

al m

usc

ula

ture

. Pe

riad

nex

al a

nd

per

ivas

cula

r ly

mp

ho

mo

no

nu

clea

r in

filtr

ates

w

ere

ob

serv

ed in

th

e su

per

ficia

l an

d d

eep

der

mis

, in

ad

dit

ion

to

nu

mer

ou

s eo

sin

op

hils

.

Aq

uam

id: I

nfla

mm

ato

ry in

filtr

ates

wer

e o

bse

rved

on

th

e d

eep

reti

cula

r d

erm

is, h

ypo

der

mis

, an

d d

erm

al

mu

scu

latu

re.

Met

aCri

ll: A

foca

l or d

iffu

se

infla

mm

ato

ry in

filtr

ate

at t

he

reti

cula

r der

mis

an

d h

ypo

der

mis

w

as o

bse

rved

.

New

-Fill

: A c

on

nec

tive

tis

sue

pre

sen

ted

d

iffu

se in

flam

mat

ory

infil

trat

e.

Art

eco

ll: A

co

nn

ecti

ve fi

bro

us

and

str

iate

d m

usc

ula

r tis

sue

pre

sen

ted

wit

h d

ense

an

d d

iffu

se

infla

mm

ato

ry in

filtr

ate.

Liq

uid

Sili

con

e: F

ibri

llar c

on

nec

tive

ti

ssu

e p

rese

nte

d w

ith

diff

use

in

flam

mat

ory

infil

trat

e.

Pitk

in e

t al

.,

2008

PM

ID:

1912

6141

UK

/Pat

ien

ts u

nd

erg

oin

g

rhin

op

last

y au

gm

enta

tio

n

451

wk,

1 m

o,

and

eve

ry

3– 6

mo

aft

er

trea

tmen

t; at

tim

e o

f rep

ort

, m

edia

n

follo

w-u

p

tim

e fo

r p

atie

nts

was

13

mo

Perm

aco

l (xe

no

gra

ft)

Nas

al re

gio

nN

ot

rep

ort

edO

ne

pat

ien

t (3

8-yr

-old

man

, ext

ern

al

app

roac

h r

hin

op

last

y) s

uff

ered

ep

ista

xis

at 1

wk

afte

r tre

atm

ent.

Seco

nd

pat

ien

t (4

2-yr

-old

man

, in

tern

al

app

roac

h r

hin

op

last

y) h

ad im

pla

nt

rem

oved

in t

he

first

po

sto

per

ativ

e w

eek.

J Am AcAd dermAtol


Ro

ssn

er e

t al

., 20

09

PMID

: 19

2073

27

Ger

man

y/Pa

tien

ts

trea

ted

wit

h a

m

eth

acry

late

-bas

ed

fille

r wh

o d

evel

op

ed

a re

acti

on

in t

he

sam

e ar

ea

34N

/AD

erm

aliv

e (h

ydro

xyet

hyl

met

hac

ryla

te

and

eth

ylm

eth

acry

late

in

fixed

co

mb

inat

ion

wit

h

hya

luro

nic

aci

d)

Fille

rs in

ject

ed in

95

area

s am

on

g t

he

34 p

atie

nts

Co

mm

on

are

as: N

LFs

(46.

3%) C

orn

ers

of t

he

mo

uth

17.

9%) G

lab

ella

(1

7.9%

) Up

per

lip

(1

2.6%

)

No

t re

po

rted

In t

he

34 p

atie

nts

, th

e m

eth

acry

late

fil

ler w

as in

ject

ed in

to 9

5 ar

eas.

Of

thes

e 95

are

as, 8

7 (9

1.6%

) sh

ow

ed

a re

acti

on

.

The

mo

st fr

equ

entl

y o

bse

rved

AEs

w

ere

the

dev

elo

pm

ent

of n

od

ule

s (n

= 8

5), d

isco

lora

tio

n (n

= 3

9),

eryt

hem

a o

r in

flam

mat

ion

(n =

32)

, an

d s

wel

ling

(n =

24)

. Mo

st n

od

ula

r re

acti

on

s w

ere

rate

d a

s se

vere

.

Mea

n t

ime

of o

nse

t w

as 2

3.1

(SD

22.

8)

mo.

Zie

lke

et

al.,

2008

PM

ID:

1817

7399

Ger

man

y/Pa

tien

ts w

ith

p

rio

r tre

atm

ents

of

der

mal

fille

rs w

ho

d

evel

op

ed a

reac

tio

n

in o

ne

or m

ore

of t

he

swel

ling

tre

ated

are

as

56 (5

5 w

om

en,

on

e m

an);

eig

ht

pat

ien

ts

wer

e ex

clu

ded

so

th

at 4

8 re

mai

ned

fo

r fu

rth

er

anal

ysis

No

t re

po

rted

Bio

deg

rad

able

fille

r, H

A,

no

nb

iod

egra

dab

le

fille

r, PM

MA

, PA

AG

, an

d

po

lyet

hyl

ene

167

trea

ted

are

as in

48

pat

ien

ts

Nas

ola

bia

l fo

ld (n

= 6

7),

follo

wed

by

the

lips

(n

= 2

7), c

orn

ers

of t

he

mo

uth

(n =

27)

, an

d

gla

bel

la (n

=16

)

No

t re

po

rted

In 1

0 p

atie

nts

, 24

area

s w

ere

trea

ted

w

ith

HA

. Th

e ar

eas

mo

st o

ften

in

ject

ed w

ere

the

NLF

s (n

= 1

5).

In re

lati

on

to t

he

nu

mb

er o

f are

as

trea

ted

wit

h H

A, t

he

mo

st fr

equ

ent

adve

rse

even

ts w

ere

swel

ling

(7

0.8%

), er

yth

ema

(66.

7%),

and

n

od

ule

form

atio

n (6

2.5%

).

In 1

3 ca

ses,

51 a

reas

wer

e in

ject

ed w

ith

PL

LA; t

he

area

s m

ost

oft

en t

reat

ed

wer

e th

e N

LFs

(n =

18)

. AEs

incl

ud

ed

no

du

les

(66.

7%),

itch

ing

(25.

5%),

and

pig

men

tati

on

(17.

6%).

In s

ix p

atie

nts

, 21

area

s w

ere

trea

ted

w

ith

PM

MA

, wit

h t

he

lip v

erm

ilio

n

(n =

8) b

ein

g t

he

area

tre

ated

mo

st

oft

en. T

he

mo

st fr

equ

entl

y o

bse

rved

A

Es a

fter

PM

MA

inje

ctio

n w

ere

no

du

les

(66.

7%),

eryt

hem

a (3

3.3%

), an

d s

wel

ling

(19.

9%).

In 1

5 p

atie

nts

, 53

area

s w

ere

trea

ted

w

ith

HEM

A. T

he

area

s m

ost

oft

en

trea

ted

wer

e th

e N

LFs

(n =

22)

. N

od

ule

s (8

6.8%

), er

yth

ema

(52.

8%),

and

pig

men

tati

on

(37.

7%) o

ccu

rred

m

ost

oft

en in

rela

tio

n to

th

e n

um

ber

of t

reat

ed a

reas

.



pp

end

ix B

. Co

nt’d

In fo

ur p

atie

nts

, 18

area

s w

ere

trea

ted

w

ith

po

lyac

ryla

mid

e; t

he

NLF

s (n

=

6) w

ere

trea

ted

mo

st o

ften

. In

re

lati

on

to t

he

nu

mb

er o

f tre

ated

ar

eas,

pig

men

tati

on

(38.

9%),

no

du

les

(38.

9%),

and

pai

n (3

8.9%

) w

ere

rep

ort

ed m

ost

oft

en a

fter

tr

eatm

ent

wit

h p

oly

acry

lam

ide.

HA

, ery

them

a, s

wel

ling,

an

d n

od

ule

fo

rmat

ion

wer

e th

e re

leva

nt

AEs

, w

ith

a m

edia

n s

ever

ity

gre

ater

th

an

0. H

A c

ause

dsi

gn

ifica

ntl

y m

ore

se

vere

ery

them

a (m

edia

n, 1

) an

d

swel

ling

(med

ian

, 2) t

han

th

e o

ther

d

egra

dab

le fi

ller P

LLA

[med

ian

for

eryt

hem

a, 0

(p =

0.0

01);

med

ian

fo

r sw

ellin

g, 0

(p =

0.0

02)]

. PLL

A

sho

wed

a m

edia

n g

reat

er t

han

0

on

ly fo

r no

du

le fo

rmat

ion

(med

ian

2)

. In

th

e n

on

bio

deg

rad

able

gro

up

, H

EMA

cau

sed

mo

re s

ever

e n

od

ule

s (m

edia

n, 3

) th

an P

MM

A (m

edia

n, 2

; p

= 0

.03)

. No

du

le fo

rmat

ion

in H

EMA

w

as a

cco

mp

anie

d b

y er

yth

ema

wit

h

a m

edia

n o

f 1.

ASP

S, A

mer

ican

So

ciet

y o

f Pla

stic

Su

rgeo

ns;

AA

D, A

mer

ican

Aca

dem

y o

f Der

mat

olo

gy;

PM

ID, P

ub

Med

iden

tific

atio

n n

um

ber

; USA

, Un

ited

Sta

tes;

N/A

, no

t ap

plic

able

; NLF

, nas

ola

bia

l fo

ld; H

IV, h

um

an

imm

un

od

efici

ency

vir

us;

VA

S, v

isu

al a

nal

og

ue

scal

e; A

Es, a

dve

rse

even

ts; L

A, l

ipo

atro

ph

y; P

LLA

, po

ly-L

-lac

tic

acid

; PA

AG

, po

lyac

ryla

mid

e g

el; P

AH

G, p

oly

acry

lam

ide

hyd

rog

el; L

IS, l

iqu

id in

ject

able

sili

con

e; C

T,

com

pu

ted

tom

og

rap

hic

; PM

MA

, po

lym

eth

ylm

eth

acry

late

; HA

, hya

luro

nic

aci

d; H

EMA

, 2-h

ydro

xyet

hyl

met

hac

ryla

te.

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