Podiatry Review Vol 71:2TECHNICAL ARTICLE page 6

Erchonia Laser Therapy in the Treatment of OnychomycosisRobert Sullivan1 and Deirdre O’Flynn2

1Clinical Director of Midleton Foot Clinic, Midleton, Ireland2Deirdre O’Flynn Senior Associate, Midleton Foot Clinic

A preliminary report on an ongoing clinical trialAbstract

This is the preliminary report of anongoing clinical trial in laser therapy usingthe Erchonia Laser for the treatment ofonychomycosis. The study has to date beencarried out on 320 patients both male andfemale with an average age of 40. There isa further 400 patients awaiting treatmentto conclude this study. The laser treatmentconsists of 4 treatments at weekly intervalusing the Lunula Laser manufactured byErchonia. This is a laser that combines twodifferent wavelengths of laser light - one at405 nm for direct fungicidal activity andone at 635 nm to stimulate a naturalimmune response - to provide effectiveclearing of the nail bed; it is claimed, withinthree months. Unlike other lasers used forthe treatment of this condition, the Lunulalaser is reported to cause no pain to thepatient treated and no temperaturechange to the area exposed to the lights.This is an eighteen month study and isongoing at this time. The treatment targetis eight hundred patients. The follow upintervals are twelve weeks post final laser,twenty four week post final laser, fifty twoweeks post final laser and finally at seventysix weeks post laser. Usual studies of thistype normally conclude in fifty two weeksor less, however, it is the aim of theresearchers to observe the nail up toseventy six weeks to ascertain the efficacyof the treatment. In the treatment to datethere has been 36 reports of side effectsand the majority 93% of patients are happywith the treatment. It is the primary aim ofthis study to present laser as an effectivetreatment for onychomycosis with a goodevidence base.

Key words: onychomycosis, fungal nailinfection, Lunula Laser,

IntroductionOnychomycosis is a persistent nail

infection of the nail bed, the nail matrixand or the nail plate, statistically it is themost common nail disorder in adultsaffecting up to 50% of patients presentingwith nail disorders (Zaias et al 1996,Schlefman 1999, Ghannoum et al 2000).Fungal skin infections account for 33% ofall skin infections (Zaias et al 1996,

Schlefman 1999). Onychomycosis is causedby dermatophytes that colanise dead skin,nail and hair tissue and nondermatophytemoulds, Candida species rarely form partof this condition (Evans 1998). The mostcommon dermatophytes seen in themycology of onychomycosis areTrichophyton rubrum and Trichophytonmentagrophytes, Trichophyton rubrum isresponsible for approximately 90% of allpresentations (Zaias et al 1996, Schlefman1999). The over all prevalence ofonychomycosis in the general populationranges from 2 to 14%. The risk of infectionincreases with age and 15 to 20% of thepopulation aged between 40 and 70, 32%of those between 60 and 70 and 48% ofthose over 70 (Schlefman 1999). Evidencesuggests that the instance ofonychomycosis in the population is on therise (Schlefman 1999, Ghannoum et al2000). There are several conditions thatpresent visually in the same way asonychomycosis including lichen planus, nailtrauma, atopic dermatitis and psoriasis.

There are many treatment options foronychomycosis; these include systemicantifungal agents, topical antifungalagents, mechanical debridement, chemicaldebridement, combinations of thesetreatments and palliative approaches. Thetreatment choice is dependent on thepractitioners training, experience andother available modalities andinterventions as well as cost (Gupta et al2003)

The treatment of advancedonychomycosis is expensive due to theinput needed from the clinician and issubject to high failure rates. Antimycoticsprescribed for the treatment ofonychomycosis are usually delivered overseveral months and have cure rates of 40 -80%, Terbinafine, Fluconoazole andIntraconazole are among the morefrequently used drugs (Gupta et al 1998,De Doncker et al 1996). These drugshowever are associated with a number ofcommon side effects such as headache,rash, gastrointestinal and endocrinedisturbances (liver) (Gupta et al 1998,Scher 1999). The usual course of drugtherapy is for three months unless a pulse

dose is used. Patients have theinconvenience of frequent blood testsduring drug therapy. Topical antifungalproducts are widely promoted on thetelevision and other media, these productsare available direct to the public without aprescription, they are safe to use andrelatively cheap, these topical products areseldom effective (Ciclopirox 2000).

Lasers have been used in medicalsettings for a considerable time. Lasersused however in the treatment ofonychomycosis have not, nor have theyundergone any rigorous examination.There has to date been no significantclinical trial carried out on a largedemographic to support the claims madeby manufacturers of laser devices claimingmarket advantage with their products. It isthe intention of this study to produce goodquality information from research that willsupport or deny the use of laser in thetreatment of onychomycosis to inform bestpractice.

This study is presented using simplestatistics expressed as a percentage, thefigures shown are as the authors and otherclinicians understand. P values etc will becalculated and extensive statistical analysismade at the end of this study. But in thisthe primary report the authors have keptit simple and basted their finding in clinicalevidence based practice.

MethodsThis clinical study relies on all subjects

having a positive mycology, therefore thereis no need for a control group as allpatients received active laser. 320 patientsor 2320 toes were subject to laserirradiation at 405nm and 635nm for twelveminutes at weekly intervals for four weeks.

Inclusion criteriaParticipation in this study is reliant on thefollowing:-

• onychomycosis present in at leastone great toenail.

• Disease involvement in the greattoenail(s) with onychomycosis of atleast 10%.

43498 Podiatry Rev Mar 20/02/2014 15:43 Page 6

Podiatry Review Vol 71:2page 7 TECHNICAL ARTICLE

• Spikes of disease extending to thenail matrix in the affected greattoenail(s).

• Proximal subungual onychomycosis.

• Distal subungual onychomycosis.

• White superficial onychomycosis.

• Patient is willing and able to refrainfrom using other (non-study)treatments (traditional oralternative) for his or her toenailonychomycosis throughout studyparticipation.

• Patient has not used othertreatments for at least 6 monthsprior to participation in the study.

• Patient is willing and able to refrainfrom the nail cosmetics such as clearand/or colour nail lacquersthroughout study.

• Male or female. 18 years of age orolder.

A copy of the study protocols is availableon request.

Exclusion criteria Patients who have used oral antifungal

medicines within 3 months prior to theadministration of the first laser treatmentare excluded from this study as are patientswho are unable to abstain from the use ofnail cosmetics. Other exclusions are nevoidsubungual formation, psoriasis of the nailplate, atopic dermatitis and lichen planus.

Treatment procedureThis treatment has two principle aims,

1.) to restore the affected nails to healthwithin the 18 month course of this study,and 2.), to eradicate the fungus from thenail and related area within the four weektreatment protocol.

As this is a positive mycology study onlypatients who test positive foronychomycosis and meet the inclusioncriteria are offered treatment. Sampleswere collected and cultured in the normalway. Patients were treated in groupsdependent on the percentage nailinclusion. The graph shows the averagepercentage amount of total nail infected at

the time of treatment in the 320 patients.All patients were given a diary to fill in everweek noting any adverse response totreatment along with and any visualchanges to the nail. No support productswere given and all subjects had to refrainfrom using any nail cosmetics for theduration of the laser active stage in thestudy.

All patients were treated as outlinedbelow at each of their four visits.

1. The foot to be treated was cleansedusing a clinell wipe.

2. Nails were clipped and reduced usinga bur where necessary.

3. The foot was cleansed to remove anydebris and dust.

4. The forefoot was photographedusing a high resolution digitalcamera. These photos were takenfrom a fixed position that wasrepeatable throughout the study.Measurements were taken from thepictures by an independent lab usingdigital measures.

It is important to note that no chemicalswere used to pre soften thickened nails asthe researchers wanted to remove anypossibility of interference from outsidesources.

This is a four week protocol where thelaser is administered on the same day eachweek for 12 minutes. All laser units areprogrammed to deliver constant therapyfor this time and then turn off.

After the pre-treatment was completethe laser therapy was administered usingthe LanulaLaserTM (Erchonia FX-405™).This is a double-headed laser with a dual-diode omitting a light wavelength of 635nm and 405 nm covering both the

ultraviolet and infrared light spectrums.The device is mains powered and stands onthe floor. The treatment area of the unit isaseptically cleaned after each patient istreated. The diagram show the, 1.) laserdiodes, 2.) the magnetic catch for closingthe unit, 3.) the heel plate which is also thedoor to the unit and 4.) the aperture intowhich the forefoot sits for the 12 minutetreatment.

Unlike other lasers applications used forthe treatment of onychomycosis noreports of any pain were made by any ofthe 320 patients (2320 toes) which havecurrently been treated.

Treatment reviews pointsIt is important to remember that this is

an 18 month study. 18 months was chosenin order to evaluate the long term effectsof the treatments and to chart anyrecurrence rate. It should be further notedthat a recurrence after a clear nail ispresented is not evidence of treatmentfailure as environmental factors must betaken into account. All patients on thisstudy are issued with a “Maintaining YourFoot Health” leaflet.

Follow up measurements were taken at12 week post final (forth) laser as well as at24, 36 (samples taken for mycology), 48,52, 64 and 76 weeks. A patient isdischarged from the study once a clear nailis presented and maintained for 12 weeks.

Interim resultsThe following graphs represent the

finding to date and show the amount ofremaining infected nail at the time ofpublication:-

Graph showing % nail inclusion Diagram showing the laser unit used

43498 Podiatry Rev Mar 20/02/2014 15:43 Page 7

Podiatry Review Vol 71:2TECHNICAL ARTICLE page 8

Of the 80 patients shown in this graph72 or 90% were discharged by week 48 asthey presented with clear nails whichremained clear for 12 weeks. None of thesepatients required additional treatments atthis time and it is expected that by week 52all will have been discharged.

The above graph shows the averageremaining infected nail at 48 week. 61 orjust over 87% of patients were dischargedfrom the study due to clear presentaton at48 weeks and 2 were recommended tohave further treatments.

At week 48, 88 patients, or just over80% were discharged from the study asthey presented with clear nails. 5 patientswere recommended to have furthertreatments.

Of the 40 patients 18 were discharged

from the study by week 48 as theypresented with clear nails, this representsa 45% success rate with 80% nail inclusion

1 was recommended further treatment.

No patients were discharged from thisgroup and all patients have beenrecommended further treatments as theyhave all seemed to reach a plateaux wherethe nail has no significant growth fromweek 36 to week 48. The average growthrate in this cohort is 51% over 36 weeks.Blood and tissue analysis was carried outon samples taken from the nail matrix andit was noted that there was a lack of fatcells at the matrix. Further investigation isongoing.

Findings from patient’s diary’sAdverse reactions from the notes of the

320 participants involved to date

• Tingling sensation during treatmentwas reported by 29 patients, allhowever said that this was slight andthe common consent was that it feltlike a vibration in the forefoot.

• 1 patient reported headache everytime the laser was activated. Glasseswere given for the frequencies usedbut the pain still persisted.

• 4 patients felt numbness to theforefoot

• 2 patients related that they haddiarrhoea that they felt was a directresult of the treatment.

The total of adverse events was 36 ofthe patients involved in this study 201 werewomen and 119 were men. 72 patientsreported using nail cosmetics during thetreatment stage of the study.

Types of Onychomycosis Onychomycosis may be classified into

several types: distal subungual, whitesuperficial, proximal subungual, endonyx,and total dystrophic.

Distal subungual onychomycosis, wasthe most common type seen in this studytoday, this involves the nail bed andsubsequently the nail plate. Whitesuperficial onychomycosis was seen assuperficial white patches with distinctedges on the surface of the nail plate.Proximal subungual onychomycosis is aresult of the fungal organism entering viathe cuticle and the ventral aspect of theproximal nail fold. In endonyxonychomycosis, fungal organisms invadethe nail plate without resulting nail bedhyperkeratosis, onycholysis, or nail bedinflammatory changes. In total dystrophiconychomycosis, complete dystrophy of thenail plate occurs; these changes may beprimary or secondary.

Data to date in plain EnglishAll of the above graphs and results are

predicated on four laser treatments over 4weeks with these results processed as perthe finding up to and including week 48.Further results will be published at the endof the study for all timelines as per theprotocol.

Graph 1

Graph 2

Graph 3

Graph 4

Graph 5

43498 Podiatry Rev Mar 20/02/2014 15:43 Page 8

Podiatry Review Vol 71:2page 9 TECHNICAL ARTICLE

Graph 1 shows the progression of the20% infected nail cohort. There were 80patients in this group, by week 48, 72 ofthese patients had been discharged andtherefore one can conclude that over 48weeks with four laser applications asuccess rate of 90% was achieved.

Graph 2 is the results of the secondtreatment cohort with 40% nail inclusion.These patients had at least 21% inclusionand show a success rate of 87% with a fourweek treatment protocol.

Graph 3 is the result drawn from thethird cohort with 60% nail inclusion. All ofthese patients had at least 41% inclusionand show a success rate of 80%, again witha four laser application.

Graph 4 shows the results of the fourthcohort with 80% nail inclusion. All of thesepatients had at least 61% inclusion andshow a success rate of 45%, with thestandard delivery protocol applied.

Graph 5 is the result of the fifth cohortwith 100% nail inclusion. No patient hasbeen discharged form this cohort at thistime but all show good growth, theaverage being 51%

From the above interim results from thisstudy it is possible to say that this type ofcold laser (Lunula Laser manufactured byErchonia) with a duel light frequency is84.25% effective over 48 week ononychomycosis for nails up to 80% effectedwith the condition, and 51% affective onnails that are totally included and orendonyx or dystrophic.

DiscussionDermatophytes cause infections of the

skin, hair and nails due to their ability toobtain nutrients from keratinised material.The organisms colonize the keratin tissuesand inflammation is caused by hostresponse to metabolic by-products. Theyare usually restricted to the nonlivingcornified layer of the epidermis because oftheir inability to penetrate viable tissue ofan immunocompetent host. Invasion doeselicit a host response ranging from mild tosevere. Acid protenases, elastase,keratinase and other proteinasesreportedly act as virulence factors(Rosenberg and Gallin 1999).

Dermatophytes are transmitted bydirect contact with infected host (human oranimal) or by direct or indirect contact withinfected exfoliated skin or hair in clothing,combs, hair brushes, theatre seats, caps,furniture, bed linens, shoes, socks, towels,hotel rugs, sauna, bathhouse, and lockerroom floors (Ajello and Getz 1954).Depending on the species the organismmay be viable in the environment for up to15 months. There is an increasedsusceptibility to infection when there is apre-existing injury to the skin such as scars,burns, excessive temperature and humidity.

Increasingly Onychomycosis is beingviewed as a more cosmetic problem aspeople become ever more conscious oftheir appearance. Fungi from the nails mayhappen before secondary bacterialinfections such as cellulitis, idiopathicreactions and chronic urticarial. Infectedtoenails may act as a reservoir for fungi,facilitations their transmission to otherparts of the body and potentially to otherpeople.

Clinical diagnosis of Onychomycosis isbased on physical examination, microscopyand culture of nail specimens. Factors suchas diabetes, hyperhidrosis, nail trauma,poor peripheral circulation; can contributeto the condition. Differential diagnosis foronychomycosis, as mentioned earlier,should be considered so as to allow theclinician to choose the most appropriatetreatment.

It has been found to date, in this study,that 4 treatments for nails up to 60%inclusion has a satisfactory outcome andthat nails with over 60% benefit fromfurther pain free treatments. The authors

of this study would agree with a recentcomment made by Kerry Zang, one of thelead developers of this laser system, Unlikeother treatment modalities, such assystemic anti-fungal agents or repeatedClass IV lasers, the Lunula cold laser systemcan be utilized as many times as necessaryto resolve the problem and can be utilizedwithout fear of any side effects or adversereactions (Zang 2013).

ConclusionLunula laser has performed consistently

throughout this study. This study is nowapproximately half way through and someend point data (18 months post last laser)is now being generated and this is lookingvery promising. The authors of this studyreport agree with Kerry Zany when he says,I believe that the Lunula laser systemstimulates the production of peroxyntritewhich interacts with the lipid portions ofthe cell membrane as well as DNA andother protein components of the invadingmicro-organisms which is cytotoxic to andinactivates the mycosis. The patientsgeneral medical condition influences therate of nail growth and the effects the risksfor re-infection. Depending on the patientsgeneral condition will determine thenumber of treatments necessary tocytotoxic to the mycosis present.

References and full study protocols areavailable on request from the principalauthor robertsullivan01@gmail.com

The above plates show the before treatment (top) and the below plates show 48 post treatments

43498 Podiatry Rev Mar 20/02/2014 15:43 Page 9