1003

ARTICLE

Submitted: Ja

From Lindenh(Rosenberg),York, USA.

Presented in

Correspondincom.

Q 2018 ASCPublished by

Visual and keratometric outcomes ofkeratoconus patients after sequential

corneal crosslinking and topography-guidedsurface ablation: Early United States experience

Alanna Nattis, DO, Eric D. Donnenfeld, MD, Eric Rosenberg, DO, MSE, Henry D. Perry, MD

Purpose: To evaluate a sequential treatment algorithm for visualand keratometric improvement in keratoconus patients aftercorneal crosslinking (CXL) followed by topography-guidedphotorefractive keratectomy (PRK).

Setting: Ophthalmic Consultants of Long Island, Garden City,New York, USA.

Design: Retrospective case series.

Methods: This study reviewed patients with keratoconus whohad CXL followed by custom topography-guided PRK betweenApril 2016 and December 2016. The following data werecollected at baseline, the time of CXL, and 3 months and6 months after PRK: uncorrected (UDVA) and corrected (CDVA)distance visual acuities, keratometric astigmatism, sphericalequivalent, maximum and mean keratometry readings, andcorneal thickness at the cone apex. Demographic data, age attime of CXL and PRK, and time elapsed between CXL and PRK

nuary 4, 2018 | Final revision submitted: May 1, 2018 | Accepted: May

urst Eye Physicians and Surgeons (Nattis), Babylon, Ophthalmic ConsultaNew York Medical College, Valhalla, Nassau University Medical Center (P

part at the ASCRS Symposium on Cataract, IOL and Refractive Surgery

g author: Alanna Nattis, DO, Lindenhurst Eye Physicians and Surgeons PC

RS and ESCRSElsevier Inc.

were analyzed for significance and a correlation with visual andastigmatic outcomes.

Results: The study comprised 56 patients (62 eyes), 34 who hadboth topographic and refractive treatment and 28 patients who hadtreatment of topographic irregularities only. The mean age was38.08 years G 13.07 (SD) at CXL and 40.33 G 13.44 years attopography-guided PRK. Six months after PRK, there was asignificant improvement in UDVA and CDVA in the refractivegroup (20/60 and 20/30, respectively) versus the nonrefractivegroup (20/100 and 20/40, respectively). Ninety-three percent ofeyes that had refractive treatment had 20/40 or better CDVA.There were no significant adverse events in any case.

Conclusions: The data support the use of refractive treatment inaddition to topographic treatment for visual improvement in pa-tients with keratoconus having CXL and PRK.

J Cataract Refract Surg 2018; 44:1003–1011Q 2018 ASCRS and ESCRS

Keratoconus is a noninflammatory progressiveectasia of the cornea characterized commonly bybilateral, asymmetric degeneration, leading to pro-

trusion and paracentral thinning.1,A Nonsurgical treat-ment of the reduced vision often seen in keratoconusincludes spectacle correction, rigid gas-permeable contactlenses, and scleral lenses. Surgical treatment modalitiesthat do not require corneal transplantation include epiker-atoplasty, photorefractive keratectomy (PRK), and intra-stromal corneal ring segment (ICRS) implantation.1

These surgical techniques might help correct refractiveerror but not halt disease progression.1 Ultimately, these

treatment modalities might correct vision for a period oftime; however, in at least 20% of patients keratoconuscan still progress to the point of requiring a penetratingkeratoplasty or deep anterior lamellar keratoplasty.1,A

Cornea crosslinking (CXL) for keratoconus has beenshown to improve the biomechanics of the cornea.1,A Itshows that the collagen is disorganized in keratoconus,leading to alteration of the refractive function, high myopia,and irregular astigmatism.1–3,A,B Keratoconic corneas alsohave increased levels of collagenolysis, loss of keratocytes,reduced collagen crosslinks, and significantly weakenedstress-versus-strain responses.1–3,A,B Wollensak et al.1

25, 2018

nts of Long Island (Donnenfeld), Garden City, the Department of Ophthalmologyerry), and Ophthalmic Consultants of Long Island (Perry), Rockville Centre, New

, Los Angeles, California, USA, May 2017.

, 500West Main Street, Babylon, New York 11702, USA. Email: asn516lu@gmail.

0886-3350/$ - see frontmatterhttps://doi.org/10.1016/j.jcrs.2018.05.020

1004 VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

found that the application of riboflavin eyedrops in eyeswith keratoconus followed by exposure to ultraviolet-A(UVA) light at a specific wavelength (370 nm, 3 mW/cm2) halted the progression of keratoconus in all patientsstudied. In addition, 70% of patients had regression, withreduction in the maximum keratometry (K) reading by2.01 diopters (D) and the refractive error by 1.14 D.1,3

The corneal and lens clarity, endothelial cell counts, andintraocular pressure remained unchanged after CXL, withimproved vision in 65% of patients.1–3,A,B

After the introduction of CXL internationally in 2003 andUnited States Food and Drug Administration approval in2016, the procedure has gained acceptance worldwide as amethod of halting the progression of ectasia in keratoconusand yielding potential visual improvement and rehabilita-tion.2,3,A,B At this time, there is no clear treatment algo-rithm for visual enhancement after CXL in keratoconus.Given the irregular contour of the cornea and the focal thin-ning that can persist after CXL, conventional or optimizedexcimer laser ablations are usually not indicated. However,to date multiple studies have shown the efficacy oftopography-guided surface ablation/PRK in patients withkeratoconus who had previous CXL.4–8

Topography-guided custom PRK is a technique using anexcimer laser to treat corneas with variable topographicindices, as in keratoconus.7–9,C–G Conventional andwavefront-guided laser therapies used for uncomplicatedlaser in situ keratomileusis and PRK work by reducingthe corneal tissue to a lower level, thus removing a greatdeal of tissue to create a more spherical cornea based onthe flattest part of the cornea.7–9,C–I This can be challenging(or impossible) in eyes with high refractive errors or signif-icant corneal irregularities.7,F,G Thus, in cases in which it isessential to correct irregularity without large tissue reservesavailable (ie, keratoconus), wavefront laser treatment is notan optimal option or is not an option at all.6–9,C–G

Topography-guided laser ablation aims to remove tissuefrom the peaks of corneal curvature with a focal myopicablation and steepen flatter areas by performing a hyper-opic ablation.4–8,C,H

Topography-guided ablation removes significantly lesstissue than wavefront-guided ablation, frequently savingone third more tissue.7–9,C–G Using this technique broadensthe spectrum of treatable patients, even those with signifi-cant surface irregularities.7–10,C–H Before treatment, an ac-curate preoperative image of the cornea is required. Inaddition, at the time of treatment, topography-guided abla-tions collect and analyze over 20 000 datapoints (as opposedto wavefront ablation, which may collect approximately1000 datapoints).7–10,C–H

Several studies have shown the efficacy of CXL per-formed simultaneously, before, or after topographic abla-tion in improving vision in keratoconus patients,although no clear treatment algorithm has been estab-lished.4–8 To our knowledge, studies evaluating a large se-ries of patients with keratoconus who have had CXLfollowed by topography-guided PRK have yet to be pub-lished. In addition, evaluation of visual and astigmatic

Volume 44 Issue 8 August 2018

outcomes based on time elapsed between CXL and ablationand examination of the influence of variables such as sex,corneal thickness, age at time of ablation, and keratometricindices on these outcomes have yet to be elucidated.The goal of this study was to evaluate the visual and astig-

matic outcomes of patients with keratoconus who had CXLfollowed by topography-guided ablation at least 3 monthslater. Based on our observations and results, we suggest atreatment algorithm for improving vision in keratoconuspatients.

PATIENTS AND METHODSThis was a retrospective case review of patients with a diagnosis ofkeratoconus who had CXL followed by custom topography-guided PRK using the Wavelight EX500 excimer laser (Alcon Sur-gical, Inc.). All surgery was performed by the same surgeon(E.D.D.) between April 2016 and December 2016 at a single-practice setting.Inclusion criteria were a history of keratoconus as obtained

from the medical record and documented by Scheimpflug tomog-raphy (Pentacam, Oculus Surgical, Inc.) as well as satisfactory im-age capture by topography (Topolyzer, Alcon Surgical, Inc.).Exclusion criteria included additional ocular procedures (extraoc-ular or intraocular) performed in the period between CXL andtopographic ablation that could influence visual and/or astigmaticoutcomes and discovered or preexisting ocular pathology,including retinal pathologies that could potentially limit visualoutcomes.

Surgical TechniqueCorneal Crosslinking Before the CXL procedure was initiated,informed consent was obtained and all questions were answered.The ocular surface was anesthetized with topical proparacaine hy-drochloride solution 0.5%. A modified epithelium-on (epi-on)technique was performed with a cotton-tipped applicator gentlyrolled over the cornea to create superficial punctate epithelial ero-sions to improve penetration of the riboflavin. Next, isotonic ribo-flavin 0.5% solution without dextran was applied to the operativeeye every 2 minutes for 1 hour, and the eye was checked at the slit-lamp for stromal riboflavin absorption and flare in the anteriorchamber. If the riboflavin saturation of the cornea was inadequate,additional riboflavin was applied and the cornea was reevaluatedbefore proceeding to UVA light application. After adequate ribo-flavin saturation was achieved, the CCL-Vario 365 system(Peschke Trade GmbH) was applied for 5 minutes (365 nm wave-length, 15 mW/cm2 fluence). After completion of treatment, abandage contact lens was placed and the patient was given oflox-acin 0.3% 4 times a day until epithelial closure, prednisolone ace-tate 1.0% drops 4 times a day for 1 week, and every day for 1 week,as well as bromfenac 0.07% 2 times a day for 3 days. All patientswere followed closely to ensure proper healing.

Photorefractive KeratectomyFor the eyes treated for both topographic abnormality and refrac-tive error, the goal was to treat the total refractive error; however, iftreating this put the patient at risk for significant corneal thinning(!300 mm), treatment was prioritized for correction of as muchcorneal cylinder, followed by sphere, as possible.Photorefractive keratectomy was not performed until the eye

appeared stable (no change in refraction or topography for at least3 months) after CXL. Before each treatment, at least 8 high-qualitytopographic images were acquired using the topography system.The technique for image acquisition and software calculation forpreoperative refractive planning has been described.8,9,E,F

After analysis by the topography system, the surgeon devised aPRK surgical plan. The goal for each patient was to not only treat

1005VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

corneal topographic irregularities but also as much refractive erroras could be safely permitted. Restrictions in treatment weredefined by a limit of astigmatic treatment by the laser (3.00 D)and a residual stromal bed (RSB) thickness of 300 mm.H If it wasdetermined that treatment of the refractive error would leave thepatient with an RSB of less than 300 mm, only topographic irreg-ularities were treated and the ablation optical zone was reducedfrom 6.5 mm to 6.0 mm to conserve corneal tissue.Photorefractive keratectomy was performed in the standard

fashion using the excimer laser. The eye was anesthetized usingtopical proparacaine hydrochloride solution 0.5%. Patients weretreated with a 6.5 mm optical zone unless the residual bed wascalculated to be 300 mm or less. In these cases, a 6.0 mm opticalzone was used. After review and confirmation of the treatmentplan, the epithelium was debrided using a blunt spatula. The eyewas centered and focused beneath the laser, the image was regis-tered, and the treatment was performed. Ofloxacin 0.3%, prednis-olone acetate 1.0%, and bromfenac 0.07% ophthalmic drops wereplaced onto the eye followed by a bandage contact lens. All pa-tients were given ofloxacin 0.3% 4 times a day until epithelialclosure, prednisolone acetate 1.0% 4 times a day tapered over1 month, and bromfenac 0.07% twice a day for 3 days. Patientswere followed closely to ensure proper healing.

Data CollectionThe following data were collected at baseline, the time of CXL, and3 months and 6 months after PRK: uncorrected distance visualacuity (UDVA); corrected distance visual acuity (CDVA); kera-tometric, manifest, and topographic astigmatism; manifest refrac-tion; spherical equivalent (SE); maximum K reading; mean Kreading; and corneal thickness (CCT) at apex of cone. Topo-graphic parameters were evaluated using the reports fromScheimpflug tomography scans. In addition, the data on age,sex, ocular history (eg, surgeries, contact lens wear), age at thetime of CXL and PRK, and the time between CXL and PRKwere analyzed for significance and a correlation with visual andastigmatic outcomes.

Statistical AnalysisStudy variables were analyzed by appropriate statistical methodsto assess for the differences between patients and eyes treated asan entire group and broken down between the refractive treatmentgroup and nonrefractive treatment group. Correlations betweendemographics (ie, age, sex) as well as baseline UDVA, CDVA,steepest K, mean K, and mean corneal astigmatism were assessedusing analysis of variance (ANOVA), the chi-square test, the t test,and the Fisher Z-transformation test to evaluate the sample corre-lation (r) for significance. For calculations, Snellen visual acuitywas converted to decimal notation. Two-way ANOVA was usedto compare UDVA and CDVA at baseline, after CXL, 3 monthsafter PRK, and 6 months after PRK. The same analysis was per-formed for the mean K readings, CCT, mean corneal astigmatism,and steepest K across all timepoints. A P value of 0.05 less or wasconsidered statistically significant.

RESULTSCharts of 62 eyes of 56 patients (36 men, 20 women) werereviewed and analyzed. Of all patients treated, 28 (50%)had the right eye treated, 22 (39%) had the left eye treated,and 6 (11%) had bilateral treatment. Thirty-four eyes of28 patients had both topographic and refractive treatment;28 eyes of 28 patients had only topographic irregularitiestreated (ie, did not have refractive error treated). Themean age at CXL was 38.08 years G 13.07 (SD) (range17 to 69 years); the mean age at time of topography-guided PRK was 40.33 G 13.44 years (range 19 to

70 years). The mean time between CXL and PRK was30.5 G 27.99 months (range 4 to 10 months). Patientswho had refractive treatment tended to be significantlyyounger at the time of CXL (34.62 G 4.52 versus42.29 G 4.81 years, respectively; P Z .021, t test) andPRK (36.56 G 4.56 versus 44.89 G 5.00 years, respec-tively; P Z .015, t test). There was no statistically signifi-cant difference between whether or not refractivetreatment was performed and the time between CXLand PRK (35.61 G 10.80 versus 26.29 G 9.48 months;P Z .198, t test). The majority of patients (35 [57.7%])were treated with an optical zone of 6.5 mm, while 27 pa-tients (42.3%) were treated with an optical zone of6.0 mm. There was no statistical correlation betweensize of optical zone treated and whether refractive treat-ment was performed (P Z .344, t test). In addition, therewas no significance between UDVA at baseline (P Z .111,t test) or immediately after CXL (P Z .596, t test) in eithergroup, whether or not refractive treatment was performed.There was no significance between CDVA at baseline(P Z .266, t test) or after CXL (P Z .651, t test) for thosetreated for refractive error versus topographic treatmentalone. Table 1 shows the overall data across all groups.

Overall CohortAfterCorneal CrosslinkingAfter CXL, there was no change inUDVA and a 1-line gain in CDVA. Corneal astigmatismdecreased by a mean of �0.41 D. The SE became more hy-peropic by C1.37 D. There mean decrease in CCT was20.2 mm. The mean K decreased by �0.05 D, and themean maximum K decreased by �0.20 D. No patientrequired retreatment after CXL.

Three Months After Photorefractive Keratectomy Comparedwith baseline values, there was no change in UDVA and a1-line gain in CDVA 3 months after PRK. There was amean change in corneal astigmatism of C0.26 D, in steep-est K of C0.50 D, in mean K of C1.50 D, and in CCTof �51.91 mm. There was a C0.33 D hyperopic shift inSE at 3 months.

Six Months After Photorefractive Keratectomy Data wereavailable for 41 eyes (26 refractive, 15 topographic treat-ment alone) at the 6-month follow-up. At this point, therewas a 1-line gain in UDVA and a 2-line gain in CDVA.There was a mean change in corneal astigmatism ofC0.29 D, in maximum K of �0.77 D, and in mean K ofC0.43 D. The CCT decreased by a mean of �58.07 mm,the SE became more hyperopic by a mean of C0.02 D.

Nonrefractive GroupThe mean age of the patients who had topographic treat-ment only was 42.49 G 12.19 years (range 19 to 69 years)at the time of CXL and 44.89 G 12.67 years (range 20 to70 years) at time of PRK. The mean time between CXLand PRKwas 35.64G 27.31months (range 3 to 98months).Table 2 shows the data across all timepoints for thesepatients.

Volume 44 Issue 8 August 2018

Table 1. Overall data across all groups and eyes (topographic alone D topographic and refractive treatment).

Parameter Baseline Post-CXL 3 Mo Post- PRK 6 Mo Post-PRK

UDVA (Snellen)

Mean 20/100 20/100 20/100 20/80

Range HM, 20/25 CF, 20/30 CF, 20/30 CF, 20/25

CDVA (Snellen)

Mean 20/50 20/40 20/40 20/30

Range 20/400, 20/20 20/100, 20/20 20/400, 20/20 20/150, 20/20

Corneal astigmatism (D)

Mean G SD 4.10 G 2.57 3.69 G 1.89 4.36 G 2.38 4.39 G 2.67

Range 0.8, 12.9 0.5, 7.9 0.9, 9.0 0.7, 12.7

Maximum K (D)

Mean G SD 54.05 G 5.58 54.25 G 4.57 54.55 G 6.07 53.28 G 4.98

Range 37.7, 70.7 43.4, 65.9 48.6, 72.4 45.5, 65.5

Mean K (D)

Mean G SD 47.37 G 4.77 47.42 G 4.60 48.87 G 5.04 47.8 G 4.09

Range 37.0, 60.2 35.2, 56.1 41.1, 62.7 40.6, 54.4

CCT (mm)

Mean G SD 483.11 G 57.43 462.91 G 61.52 431.2 G 65.16 425.04 G 50.61

Range 371, 643 360, 651 279, 525 312, 537

SE (D)

Mean G SD �5.88 G 6.21 �4.51 G 3.99 �5.55 G 3.91 �5.86 G 3.76

Range �23.87, C2.38 �15.50, C3.36 �15.00, C1.00 �13.50, �0.25

20/40 or better UDVA (%) 11 7 14 6

20/40 or better CDVA (%) 51 55 57 69

CCT Z central corneal thickness (apical corneal thickness); CDVA Z corrected distance visual acuity; CF Z counting fingers; HM Z hand motions;K Z keratometry; SE Z spherical equivalent; UDVA Z uncorrected distance visual acuity

1006 VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

After Corneal Crosslinking After CXL, 1 line of UDVA waslost and there was no change in CDVA. There was amean change in corneal astigmatism of �0.25 D, in

Table 2. Data across all timepoints for patients treated for topog

Parameter Baseline Post-CX

UDVA (Snellen)

Mean 20/80 20/100

Range HM, 20/25 20/400, 20

CDVA (Snellen)

Mean 20/40 20/40

Range 20/400, 20/20 20/100, 20

Corneal astigmatism (D)

Mean G SD 4.19 G 2.07 3.94 G 1

Range 0.9, 8.5 0.5, 7.3

Maximum K (D)

Mean G SD 54.46 G 6.44 55.33 G 4

Range 37.7, 70.7 44, 64.

Mean K (D)

Mean G SD 47.42 G 5.48 47.31 G 5

Range 37.0, 60.2 35.2, 58

CCT (mm)

Mean G SD 475.06 G 62.09 455.36 G 6

Range 372, 643 352, 65

SE (D)

Mean G SD �6.16 G 6.14 �4.13 G 4

Range �18.63, 2.38 �14.38, 3

20/40 or better UDVA (%) 18 12.5

20/40 or better CDVA (%) 66 64

CCT Z central corneal thickness (apical corneal thickness); CDVA Z correcteK Z keratometry; SE Z spherical equivalent; UDVA Z uncorrected distance vis

Volume 44 Issue 8 August 2018

maximum K ofC0.87 D, and in mean K of�0.11 D. Therewas a mean hyperopic change in SE ofC2.03 D and a meanchange in CCT of �19.7 mm.

raphic irregularities alone.

L 3 Mo Post-PRK 6 Mo Post-PRK

20/100 20/100

/30 CF, 20/50 CF, 20/50

20/50 20/40

/20 20/400, 20/25 20/150, 20/20

.97 4.78 G 2.61 4.77 G 2.72

0.9, 9.0 0.7, 12.7

.64 54.00 G 3.66 54.44 G 5.16

9 49.1, 61.1 45.5, 64.4

.36 48.29 G 4.71 48.09 G 4.63

.2 41.1, 55.25 40.6, 57.5

3.82 425.5 G 65.71 423.33 G 51.88

2 364, 525 312, 537

.27 �7.37 G 4.38 �7.16 G 3.99

.37 �15.38, 0.50 �12.88, 0.25

0 0

38 54

d distance visual acuity; CF Z counting fingers; HM Z hand motions;ual acuity

1007VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

Three Months After Photorefractive Keratectomy Comparedwith baseline, there was 1 line of UDVA and CDVA lost.There was a mean change in corneal astigmatism ofC0.59 D, in maximum K of �0.46 D, and in mean K ofC0.87 D. There was a mean myopic change in SE of�1.21 D and a mean change in CCT of �49.56 mm.

Six Months After Photorefractive Keratectomy Six months af-ter PRK, there was no change in UDVA or CDVAcompared with baseline. There was a mean change incorneal astigmatism of C0.58 D, in maximum K ofC0.02 D, and in mean K of C0.67 D. There was a meanmyopic change in SE of �1.00 D and a mean change inCCT of �51.73 mm.

Refractive GroupThe mean age at CXL of patients treated for both topo-graphic abnormality and refractive error was34.62 G 12.75 years (range 17 to 65 years) at the time ofCXL and 36.56 G 12.87 years (range 19 to 67 years) attime of PRK. The mean time between CXL and PRK was26.29 G 27.81 months (range 4 to 105 months). Table 3shows the data across all timepoints for eyes treated forrefractive error and topographic irregularities.

After Corneal Crosslinking There was no change in UDVAfrom baseline to post-CXL, while there was a 1-line gainin CDVA. Corneal astigmatism decreased by a mean of0.60 D, which was accompanied by a mean change of�0.38 D in maximum K and ofC0.21 D in mean K. Therewas a mean hyperopic shift in SE of C0.80 D and a meanchange in CCT of �17.45 mm.

Table 3. Data for eyes treated for refractive error and topographi

Parameter Baseline Post-CX

UDVA (Snellen)

Mean 20/100 20/100

Range CF, 20/40 HM, 20/5

CDVA (Snellen)

Mean 20/50 20/40

Range 20/400, 20/25 20/100, 20

Corneal astigmatism (D)

Mean G SD 4.04 G 2.92 3.44 G 1

Range 0.8, 12.9 0.5, 7.9

Maximum K (D)

Mean G SD 53.71 G 4.71 53.33 G 4

Range 41.7, 59.1 43.4, 65

Mean K (D)

Mean G SD 47.33 G 4.13 53.33 G 4

Range 37.9, 56.6 36.4, 51

CCT (mm)

Mean G SD 488.19 G 53.68 470.74 G 5

Range 384, 642 360, 64

SE (D)

Mean G SD �5.64 G 6.25 �4.84 G 3

Range �23.87, C2.25 �13.88, C

20/40 or better UDVA (%) 5 0

20/40 or better CDVA (%) 39 62.5

CCT Z central corneal thickness (apical corneal thickness); CDVA Z correcteK Z keratometry; SE Z spherical equivalent; UDVA Z uncorrected distance vis

ThreeMonths After Photorefractive KeratectomyAt 3 months,UDVA and CDVA had both improved by 2 lines. Cornealastigmatism decreased by 0.62 D, which was accompaniedby a mean change of C2.47 D in maximum K and ofC3.17 D in mean K. There was a mean hyperopic shift inSE of C1.95 D and a mean change in CCT of �34.19 mm.Compared with the nonrefractive group at this time-

point, there was a significant improvement in UDVA andCDVA (P Z .007 and PZ .004, respectively; t test). Therewas a significant improvement in SE (toward emmetropia)3 months after PRK in the refractive group versus the non-refractive group (P ! .001, t test).

Six Months After Photorefractive Keratectomy At 6 months,there was a mean 3-line improvement in UDVA and a2-line improvement in CDVA. There was a mean changein astigmatism of �0.63 D, in steepest K of �3.40 D, andin mean K of �0.36 D. The CCT decreased by a mean of�58.76 mm, and the SE became more hyperopic by amean of C1.59 D.There was a significant improvement in UDVA (P! .001,

t test) andCDVA (PZ .049) in the refractive group versus thenonrefractive group 6 months after PRK. In addition, therewas a significant improvement in SE (toward emmetropia)at 6 months after PRK in the refractive group versus the non-refractive group (PZ .014, t test). Figures 1 and 2 show sam-ple topographies of 1 refractive patient who had visualimprovement as well as clear improvements in keratometryand topography. This patient had a preoperative SnellenUDVA of 20/100 and CDVA of 20/50. At the 6-monthfollow-up, the UDVA was 20/70 and the CDVA was 20/30.

c irregularity.

L 3 Mo Post-PRK 6 Mo Post-PRK

20/70 20/60

0 20/400, 20/30 20/100, 20/25

20/30 20/30

/25 20/100, 20/20 20/150, 20/20

.78 3.42 G 1.35 3.41 G 2.26

0.9, 5.25 0.75, 7.8

.29 56.18 G 10.18 50.31 G 2.79

.9 47.25, 72.4 47.2, 55.3

.29 50.50 G 5.58 46.97 G 1.55

.2 44.7, 62.7 44.8, 49

8.35 454 G 57.56 429.43 G 46.91

8 374, 507 335, 493

.69 �3.69 G 2.70 �4.05 G 2.53

0.50 �6.63, C1.00 �12.00, �1.25

19 14

73 93

d distance visual acuity; CF Z counting fingers; HM Z hand motions;ual acuity

Volume 44 Issue 8 August 2018

Figure 1. Preoperative (after corneal crosslinking)topography shows keratoconus and irregular astig-matism.

1008 VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

In addition, the tomography shows the smoothing effect oftopography-guided PRK.

Other Statistical ConsiderationsThere was no significant correlation between maximum K,UDVA,CDVA, or corneal astigmatism and age at baseline, af-ter CXL, 3 months after PRK, or 6months after PRK. In addi-tion, there was no statistical correlation between eye treatedand whether or not refractive treatment was performed.

Volume 44 Issue 8 August 2018

There was no statistically significant difference in cornealastigmatism, CCT, maximum K, or mean K between therefractive group and nonrefractive group at baseline(PZ .837, PZ .472, PZ .640, and PZ .942, respectively),after CXL (P Z .343, P Z .372, P Z .110, and P Z .854,respectively), 3 months after PRK (P Z .165, P Z .533,P Z .467, and P Z .303, respectively), or 6 months afterPRK (P Z .27, P Z .486, P Z .067, and P Z .549,respectively).

Figure 2. Tomography 6 months after topography-guided photorefractive keratectomy showsimprovement in corneal astigmatism and increasedcorneal surface regularity.

1009VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

There was a statistically significant improvement in SEtoward emmetropia 3 months and 6 months after PRK inthe refractive group versus the nonrefractive group(P ! .001 and P Z .014, respectively). However, therewas no detectable difference between the 2 groups at base-line or after CXL (P Z .770 and P Z .501, respectively).The mean K at baseline did not appear to have a statisti-

cally significant influence on UDVA or CDVA 6 months af-ter PRK (PZ .970 and PZ .439, respectively). There was nostatistical correlation between maximum K at baseline andUDVA (PZ .771) or CDVA6months after PRK (PZ .303).There was no statistical correlation between corneal

astigmatism or CCT at baseline and UDVA (P Z .725and PZ .191, respectively) or CDVA after PRK at 6months(P Z .983 and P Z .614, respectively).

DISCUSSIONOur data are in concordance with results in previous studiesshowing the efficacy and potential visual improvement inkeratoconus patients having CXL and PRK.4–8,10–17,J It iswell established that alterations in corneal shape have a sig-nificant refractive effect requiring multifaceted patient-specific treatment planning.10,12–19,G,J

Support of this treatment algorithm is found in several pub-lished case reports by Krueger and Kanellopoulos7 and Kanel-lopoulos and Binder8 that report the efficacy of coupledtopography-guided PRK and CXL in eyes with corneal irreg-ularities (eg, after transplantation, in keratoconus). In thesecases, topography-guided ablation provided a customapproach that effectively treated the measured extremecorneal irregularities.8 In a 2016 American Society of Cataractand Refractive Surgery presentation, Holland and LinJ estab-lished that transepithelial PRK with simultaneous CXL in pa-tients with keratoconus was efficacious, with 50% of eyesachieving a UDVA of at least 20/40. In addition, 62% hadimproved CDVA by 2 or more lines and a mean reductionin SE by �2.74 D. The best outcomes were in patients withcentral irregular astigmatism, and a combination of CXLand topography-guided PRK offered improved UDVA andCDVA to patients with keratoconus, ectasia, or “regular cor-neas” with a low CCT.J Studies by Sakla et al.12,14 also foundsignificant improvement in the manifest refraction, UDVA,CDVA, and K values over baseline with simultaneous CXLand topography-guided PRK, while Knezovi�c et al.13 foundthat partial topography-guided PRK combined with CXLled to an improvement in CDVA of 4 lines.In the present study, we found there was a modest gain in

UDVA and CDVA overall. However, when separatingthose treated for solely topographic irregularities and thosetreated for refractive error, the latter set of patients had sig-nificant visual and astigmatic improvement, with a 3-lineaverage gain in UDVA and a 2-line average gain inCDVA. In addition, at the end of the 6-month period, ofeyes whose treatment included some degree of refractivecorrection, 93% had a CDVA of at least 20/40 or betterand a statistically significant improvement in SE.Despite visual improvement, the amounts of corneal

astigmatism, mean K values, and maximum K values after

PRK in the nonrefractive group increased. Although coun-terintuitive, this might be the result of treating topographicirregularities in this population rather than creating a com-plete flattening effect, as seen in wavefront-guided thera-pies. In inferior cones, the myopic ablation is also inferiorto the visual axis, which can create a hyperopic profilethat increases central steepening. Therefore, the treatmentmight have created a mild amount of increased cornealsteepening as measured by Scheimpflug tomography. It isalso possible that while aiming to steepen the flat areas ofthe cornea, overall steepness was increased, leading to ourfindings. In addition, those treated for refractive error haddecreased amounts of astigmatism (cornea, mean K,maximum K), which is consistent with the refractive errorbeing treated. As seen in Table 3, at the 3-month mark inthe refractive group, the SE trended more toward emmetro-pia while the maximum K values increased. This was fol-lowed by an overall decrease in maximum K values and aslight myopic shift in SE at 6 months after PRK. This couldhave been secondary to corneal remodeling after PRK aswell to as variability in data secondary to the smaller sampleof patients at 6 months. More research into the cornealbiomechanics and remodeling after topography-guidedPRK is necessary to elucidate the exact cause of the relativeincrease in corneal astigmatism.The findings that baseline mean K, maximum K, corneal

astigmatism, and CCTdid not appear to influence final visualoutcome (UDVAor CDVA) are unique to our study and wasnot addressed in previous studies.4–10,12–15,18,19,D,F,G,J This isan interesting finding because we would expect patientswith lower baseline astigmatism to have proportionately bet-ter outcomes. In concert with this, we would expect patientswith thicker corneas to have potentially better outcomesbecause they have “more room to treat” based on necessarytissue availability for refractive treatment. Each keratoconuspatient in our study had varying amounts of corneal astigma-tism and corneal thickness at baseline; thus, these findingsalso support the usefulness of topography-guided PRK acrossa wide range of patients. Based on these findings, the treat-ment appeared to be equally efficacious across the variancein corneal astigmatism and CCT values. However, furtherstudies would be useful in elucidating the validity and repro-ducibility of these results using a larger sample.Comparison of the 2 groups (refractive versus non-

refractive) showed that treatment of refractive errorsignificantly improved visual results. Although visualimprovement was not as great in the nonrefractivegroup, many of the patients were able to more comfort-ably resume contact lens wear and even noted increasedquality of vision after treatment. It is possible that intreating topographic irregularities, some higher-orderaberrations (HOAs) were decreased or eliminated, allow-ing for better visual quality, although this was notformally addressed in our study.9,G,H Analysis of HOAsbefore and after topography-guided treatment wouldbe needed to show this hypothesized effect and couldbe performed in future studies. No patient had anadverse event, such as infection, scarring, or excessive

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1010 VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

corneal thinning, after treatment or during the follow-upperiod.Although many studies have performed simultaneous

topography-guided PRK and CXL,7,8,10,12–14,16,17,19,F webelieve it is important to allow the cornea to stabilize be-tween treatments. It has been shown that the cornea un-dergoes significant remodeling after CXL, and this canaffect not only refractive planning but also postoperative re-sults. Waiting for post-CXL stabilization not only ensuresthat the corneal topography has stabilized but might alsoreduce the risk for adverse events such as delayed healingwhen combining CXL with excimer laser photoablation,as noted in previous reports.8,10,13,15–17

In concordance with results in previous studies, customtopography-guided PRK for keratoconic eyes after CXLwas safe and effective in our patients. Topography-guidedPRK performed at least 3 months after CXL treatment pro-duced an average 2-line improvement in UDVA, 2-lineimprovement in CDVA, and for those treated for refractiveerror, a 3.00 D improvement in the steepest K values at6 months. In addition, when both refractive and topographicerrors were treated, 93% of patients achieved a CDVA of 20/40 or better. We have also noted that in cases in which therefractive error will not permit a full correction (eg, insuffi-cient stromal bed thickness), a proposed treatment of onlythe irregular astigmatic component can significantly improvethe CDVA outcomes, but not necessarily the UDVA.Given that topography-guided treatment is based on ob-

taining good quality preoperative topographic images, theocular surface should be optimized and if necessary, treatedbefore further intervention.4,5,7–9,G In addition, when usingtopography-guided ablation in irregular eyes, there may besome residual hyperopia or myopia.4,5,7,8,12–19,F,J In thesecases, it should be thoroughly explained to patients that asecond refining laser treatment to address residual refrac-tive error might be considered as long as there is a sufficientRSB and a good topographic image can be ob-tained.4,5,7,8,12–19,F,J We advocate the use of a large ablationzone and prefer a 6.5 mm optical zone. However, whenthere is an insufficient RSB, use of a small (6.0 mm) opticalzone can be an effective in conserving corneal tissue. Pa-tients should be informed that after PRK, epithelial remod-eling (both hyperplasia and hypoplasia) occurs andimprovement of vision can continue for up to6 months.9,12–14,16–19,J Although other studies have shownthe long-term efficacy of topography-guided PRK as atreatment post-CXL (and its use in addition to other treat-ment modalities,6–8,12–17 such as ICRS or phakic toricintraocular lens implantation), a study of long-termfollow-up of these patients using our sequential techniqueis necessary to show stability of refraction and visual acuityin this patient population. Another consideration in post-CXL patients is that the laser treatment should be appliedwith caution because the cornea might have different abla-tion behavior from that of a normal cornea.7,8,12–14,16–19

For this reason, it has been recommended that thesurgeon undercorrect the sphere and cylinder by25%.4,5,7,8 More studies are needed to further understand

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the behavioral characteristics of post-CXL eyes having sur-face ablation.It is important tohighlight that our studyuse amodified epi-

on acceleratedCXL technique,whichdiffers from the standardDresden protocol.1,4,11 Although multiple studies20–24 havevalidated accelerated and transepithelial CXL, using this tech-nique as performed in our study might have affected some re-sults. Among possible changes in corneal architecture withtransepithelial CXL is corneal epithelial remodeling, whichcan differ from traditional epithelium-off (epi-off) CXL.20–24

Also, some studies20–23 report that CXL does not penetrateas deeply into the stroma if it is performed epi-on, and there-fore, corneal astigmatism, curvature, and the response to abla-tion might differ as well. More corneal flattening is seen inconventional epi-off CXL than in transepithelial CXL.20–24

Therefore, this might produce variability in K readings, asseen in our study.20–24 Based on our literature search, theredoes not appear to be a head-to-head trial of our modifiedepi-on CXL technique versus traditional epi-off CXL followedby topography-guided PRK to evaluate possible, and likelysubtle topographic, changes secondary to the CXL technique.In addition, although transepithelial CXL was performed, allpatients had a stable refractive error and corneal astigmatismbefore treatment for topography-guided PRK was planned.We believe that epithelial analysis after CXL (both modifiedepi-on and standard epi-off) as well as measurements ofcorneal flattening in a head-to-head trial would be not onlyinteresting but also of benefit in determining whether themethod of CXL is truly significant and which CXL strategyserves as a better surgical foundation before PRK treatment.Our study adds to current literature because it is the largest

U.S. case series showing the safety and efficacy of topography-guidedPRK inkeratoconuspatients afterCXL.Weperformedour treatment in a stepwise approach to allow for regulariza-tion of the corneal surface after CXL before taking preopera-tive measurements for PRK. We strongly believe thistreatment algorithm allows for better preoperative planningas well as more accurate postoperative results.

WHAT WAS KNOWN� Cornea crosslinking for keratoconus has been shown toimprove corneal biomechanics.

� Given the irregular contour of the cornea as well as focalthinning that can persist after CXL, conventional excimerlaser ablations are usually not indicated.

WHAT THIS PAPER ADDS� At least 3 months after CXL, or once cornea topography andrefraction have stabilized, topography-guided PRK appearsto be an efficacious and safe method of visual improvementin keratoconus patients.

� When there is sufficient stromal bed, the refractive compo-nent should be treated in addition to the topographicablation.

� More than 90% of patients achieved a CDVA of at least 20/40 after the use of PRK to treat refractive error in kerato-conus patients as well as topographic irregularities afterCXL.

1011VISUAL AND KERATOMETRIC OUTCOMES OF CXL FOR KERATOCONUS

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Disclosures: None of the authors has a financial or proprietary in-terest in any material or method mentioned.

First author:Alanna Nattis, DO

Lindenhurst Eye Physicians and Surgeons,Babylon, New York, USA

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