ORIGINAL ARTICLES

Phototherapeutic keratectomy versus mechanical epithelialremoval followed by corneal collagen crosslinking forkeratoconusMustafa Kapasi, BSc (Hons), MD, Jasrabir Baath, MD, George Mintsioulis, MD, FRCSC,W. Bruce Jackson, MD, FRCSC, Kashif Baig, MD, MBA, FRCSC

ABSTRACT ● RÉSUMÉ

Objective: To compare the visual outcomes of patients with keratoconus treated with either phototherapeutic keratectomy (PTK) ormechanical epithelial removal prior to corneal collagen crosslinking (CXL).

Design: Comparative study.Participants: The records of 34 patients (34 eyes) who had PTK (17 eyes) or mechanical (17 eyes) epithelial removal prior to CXL for

keratoconus were reviewed retrospectively.Methods: CXL was performed by 1 of 3 surgeons (G.M., W.B.J., or K.B.). Of the eyes, 17 had undergone mechanical epithelial removal

prior to CXL and were consecutively selected, after matching with the 17 eyes in the PTK group, for the variables of procedure date,average keratometry, and pachymetry. All eyes had central cones. Manifest refraction spherical equivalent, sphere, cylinder,best-corrected distance visual acuity, and pachymetry were measured and compared preoperatively and in follow-up.

Results: The mean change between the pre- and postoperative manifest refraction spherical equivalent for the PTK and mechanicalgroups was 1.68 � 0.80 and 0.26 � 0.90, respectively (p � 0.05). The mean change between pre- and postoperative cylinder for thePTK and mechanical groups was 0.53 � 0.28 and 0 � 0.18, respectively (p � 0.05). The mean number of lines of improvement inthe PTK and mechanical groups were 0.33 � 0.82 and �0.58 � 0.45 lines, respectively (p � 0.05).

Conclusions: Early results suggest that CXL with laser epithelial removal is superior to CXL with mechanical epithelial removal because it reducesrefractive error in qualified patients. Although not statistically significant, there was also a trend for PTK CXL patients to have better visualoutcomes.

Objet : Comparaison entre les résultats visuels des patients atteints de kératocône traités soit par kératectomie photothérapeutique(KPT) ou par retrait mécanique de l’épithélium avant la réticulation du collagène cornéen (RCC).

Nature : Étude comparative.Participants : Examen rétrospectif de 34 patients (34 yeux) qui avaient eu une KPT (17 yeux) ou un retrait mécanique de l’épithélium

(17 yeux) avant la RCC pour kératocône.Méthodes : La RCC a été pratiquée par un des 3 chirurgiens (G.M., W.B.J. ou K.B.). Parmi les yeux, 17 qui avaient subi un retrait

mécanique de l’épithélium avant la RCC ont par la suite été retenus de façon consécutive parce qu’ils correspondaient au groupe des17 ayant eu une KPT, en regard des variables de la date de procédure, de la moyenne de kératométrie et de pachymétrie. Tous lesyeux avaient un cône central. L’équivalent sphérique de la réfraction manifeste, la sphère, le cylindre, la meilleure acuité visuellecorrigée et la pachymétrie ont été mesurés et comparés avant l’opération et durant le suivi.

Résultats : La moyenne de changement entre l’équivalent sphérique de réfraction manifeste sphérique des groupes KPT et retrait mécanique étaitde 1,68 � 0,80 et 0,26 � 0,90, respectivement (p � 0,05). La moyenne de changement du cylindre avant et après l’opération pour les groupesKPT et retrait mécanique était de 0,53 � 0,28 et 0 � 0,18, respectivement (p � 0,05). La moyenne du nombre de lignes d’amélioration dans lesgroupes KPT et retrait mécanique était de 0,33 � 0,82 et -0,58 � 0,45 lignes, respectivement (p � 0,05).

Conclusions : Les premiers résultats suggèrent que la RCC avec retrait épithélial au laser est supérieure à celle obtenue par retraitépithélial mécanique, parce qu’elle réduit l’erreur réfractive chez les patients désignés. Bien que cela ne soit pas statistiquementsignificatif, les patients ayant reçu une RCC par KPT auraient aussi tendance à avoir un meilleur résultat visuel.

Collagen crosslinking (CXL) was developed to increasethe biomechanical stability through the formation of cross-links between and within corneal collagen fibres inducedby the photomediators riboflavin and ultraviolet-Alight.1,2 Wollensak et al. were able to show that the inter-action between these photomediators caused the forma-tion of reactive oxygen species, which induced the forma-tion of new covalent bonds, thereby strengthening thecollagen matrix of the cornea.3 They also demonstrated theimportance of epithelial removal prior to CXL in order toachieve adequate stromal absorption of riboflavin, which is

From the Department of Ophthalmology, University of Ottawa, Ottawa,Ont.

Originally received Nov. 10, 2011. Final revision Feb. 23, 2012. AcceptedMar. 26, 2012Correspondence to Kashif Baig, The Ottawa Hospital, Suite 6281, Box 307,

501 Smyth Rd., Ottawa ON K1H 8L6; kbaig@toh.on.ca

344 CAN J OPHTHALMOL—VOL. 47, NO. 4, AUGUST 2012

of paramount importance to the efficacy of the crosslink-ing process.4

Excimer laser phototherapeutic keratectomy (PTK) modehas been successfully used to remove the epithelium prior torefractive surgery, as well as to treat a number of conditions ofthe anterior cornea, including anterior corneal scars,5 dystro-phies of the corneal epithelium and Bowman’s membrane,6-9

anterior stromal dystrophies,10 and elevated corneal lesions,including keratoconus nodules.11,12

Traditionally, mechanical epithelial removal using anAmoils brush or similar device has been used in CXL.

Can J Ophthalmol 2012;47:344–3470008-4182/11/$-see front matter © 2012 Canadian Ophthalmological Society.Published by Elsevier Inc. All rights reserved.dx.doi.org/10.1016/j.jcjo.2012.03.046

Phototherapeutic keratectomy for keratoconus—Kapasi et al.

Transepithelial PTK utilizes the excimer laser to removethe epithelium as well as smooth out the irregular anteriorcornea.13 Reinstein et al. described an epithelial doughnutpattern in keratoconic eyes with epithelial thinning overthe cone surrounded by a region of epithelial thickness.They found this pattern to be consistent with an underly-ing stromal cone.14 Because of this phenomenon, PTKepithelial removal at a constant depth removes some stro-mal tissue at the top of the cone in addition to epithelium,thereby providing the smoothing effect.

In this study, we present retrospective data from 17 pa-tients who received transepithelial PTK prior to CXL, andwe compare their outcomes with 17 patients who receivedmechanical epithelial removal prior to CXL.

METHODS

The charts of 34 patients (34 eyes) whose cases datedfrom September 2010 to August 2011 were retrospectivelyreviewed. Of those patients, 17 (17 eyes) underwent PTKepithelial removal prior to crosslinking, whereas the other17 patients (17 eyes) received mechanical epithelial re-moval. Patients in the group receiving mechanical CXLwere consecutively selected after matching for the variablesof procedure date (September 2010 to August 2011), kera-tometry (within the minimum and maximum values of thePTK group), and pachymetry (within the minimum andmaximum values for central corneal thickness [CCT] andthinnest corneal thickness [TCT] as measured by usingScheimpflug [Pentacam, Oculus, Wetzlar, Germany] im-aging of the PTK group). Data were reviewed preopera-tively and 1 month postoperatively. Data collected in-cluded demographic data (age and sex); type of epithelialremoval; uncorrected and best-corrected distance visualacuity (UDVA) and corrected distance visual acuity(CDVA), respectively; sphere refraction; astigmatism;keratometry (minimum, maximum, and average); CCT;and TCT. All patients included in this study had centralcones as determined by Scheimpflug imaging. This studywas approved for retrospective review by the Ottawa Hos-pital Research Ethics Board.

Inclusion criteria included patients who were betweenthe ages of 14 and 60 years of either sex and had keratoco-nus, as defined by keratometry, astigmatism, or myopicshift in addition to consistent topographic data. Exclusioncriteria included current or planned pregnancy; current orrecent use of Accutane; known allergy; previous cornealsurgery, including intrastromal corneal ring segments orcorneal transplantation; ocular conditions that may predis-pose the eye to further complications (e.g., herpes simplex,herpes zoster, recurrent corneal erosion syndrome, cornealulcer, clinically significant corneal scarring in treatmentzone, etc.); TCT � 400 �m; history of delayed epithelialhealing; and nystagmus or other conditions preventingsteady gaze. Preoperative evaluation consisted of ocular

history, slit-lamp examination, tonometry, UDVA and

CDVA measurements, and Scheimpflug imaging to collecttopographic and pachymetry measurements. Postoperativeexamination consisted of all of the same tests except theScheimpflug imaging.

All patients received Vigamox (moxifloxacin 0.5%) (Al-con Laboratories, Fort Worth, TX) for 2 days prior totreatment. All procedures were performed by 1 of 3 sur-geons (K.B., G.M., or W.B.J.) at the University of OttawaEye Institute under clean conditions. One drop of each ofthe following was given prior to the commencement of theprocedure: Vigamox (moxifloxacin 0.5%) (Alcon); isopto-carpine (pilocarpine hydrochloride 2%) (Alcon); andchloramphenicol (Minims; tetracaine hydrochloride0.5%) (Bausch & Lomb, Rochester, NY). In addition,1 mg of lorazepam was given by mouth to calm the patient.Ultrasonic pachymetry (Pachette, DGH Technology, Ex-ton, PA) was taken 4 times (3 samples per session, lowestvalue taken) during the procedure: preprocedure, post ep-ithelial removal, and 15 and 30 minutes after the start ofriboflavin drops.

Transepithelial PTK was performed at a constant depthof 50 �m, in a 6.5 mm central zone, and at 8 Hz, usingautocentration for all patients in the PTK group using theexcimer laser (Star S4 IR, Visx, Abbott Medical Optics,Santa Ana, CA). Mitomycin C 0.02% (MMC) was thenapplied for 30 seconds. In the mechanical group, the epi-thelium was removed using an Amoils brush, but noMMC was used.

If pachymetry was � 400 �m, 0.1% riboflavin (0.1%solution of 10 mg riboflavin-5-phosphate) in 0.5% IsoptoTears (Alcon) was used. If pachymetry was noted to be �400 �m at any time during the procedure, hypotonic0.1% riboflavin in a balanced salt solution (BSS) was useduntil pachymetry was sampled at � 400 �m. Riboflavinwas applied every 3 minutes for 30 minutes to ensure com-plete stromal penetration. Calibration to 3.0 mW/cm2 wascompleted using a meter (YK-34UV, Lutron ElectronicEnterprise, Taipei, Taiwan) supplied with the UV-X sys-tem (Koehler Optics, version 1000, IROC, Zurich,Switzerland). UV-A was then applied for 30 minutes onlyif pachymetry was � 400 �m. Riboflavin drops continuedthrough the UV-A treatment at a constant rate of 1 dropevery 3 minutes. Throughout the procedure, tetracaineand BSS were used as needed. The procedure was com-pleted with a BSS flush.

Postoperatively, a bandage contact lens was applied for 1week with Vigamox (moxifloxacin 0.5%; Alcon) 4 timesper day. FML (fluorometholone 0.1% [Allergan, Irvine,CA]) was given 4 times per day on a tapering schedule for1 month.

RESULTS

The study consisted of 27 males and 7 females with anaverage age of 31.6 � 1.8 years (range, 16 to 60). The

mean preoperative CCT for the PTK group was 477 �

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Phototherapeutic keratectomy for keratoconus—Kapasi et al.

7.1� (range, 430 to 519�). For the mechanical group, themean preoperative CCT was 489 � 5.6� (range, 454 to517�). The mean preoperative TCT for the PTK and me-chanical groups were 450 � 8.2� (range, 404 to 512�)and 458 � 7.9� (range, 406 to 506�), respectively. Aver-age Keratometry (K) for the PTK and mechanical groupspreoperatively were 50.9 � 1.26 (range, 42.9 to 65.8) and49.5 � 0.82 (range, 44.4 to 54.9), respectively. These re-sults were not statistically significant (p � 0.05, pairedt test).

Visual acuity is expressed in decimals. The mean preop-erative CDVA in the PTK group was 0.576 � 0.070(range, 0.03 to 1.00), whereas the mean 1-month post-operative CDVA in the same group was 0.608 � 0.069(range, 0.33 to 1.00). In the mechanical group, the meanpreoperative and 1-month postoperative CDVAs were0.696 � 0.064 (range, 0.29 to 1) and 0.672 � 0.073(range, 0.29 to 1), respectively. In both the PTK and me-chanical groups, the change in vision preoperatively and1-month postoperatively was not statistically significant(p � 0.05, paired t test). Table 1 shows these results.

The mean change between the preoperative and the1-month postoperative manifest refraction sphericalequivalent (MRSE) for the PTK group was 1.68 � 0.80(range, �1.88 to 9.13), and the mean change in MRSE forthe mechanical group was 0.26 � 0.90 (range, �6.13 to7.88). Cylinder change in the PTK and mechanical groupswas 0.53 � 0.28 (range, �6.75 to 1.75) and 0 � 0.18(range, 0.75 to 1.25) diopters, respectively. Both these re-sults were statistically significant, with the PTK group hav-ing significantly better outcomes in MRSE and cylinderchange 1 month postoperatively than the mechanicalgroup (p � 0.023, p � 0.04, respectively; paired t test).

In the same time frame, the mean change in sphere forthe PTK and mechanical groups was 0.27 � 0.60 (range,�2 to 5.5) and 0.045 � 0.19 (range, �1.25 to 1) diopters,respectively. The mean number of lines of improvement ofCDVA in the PTK and mechanical groups were 0.33 �0.82 lines and �0.58 � 0.45 lines, respectively. Theseresults were not statistically significant (p � 0.05, paired ttest) but there was a trend for subjects in the PTK group tohave more lines of improvement than those in the mechan-ical group.

The mean change in epithelial thickness prior to and

Table 1—Preoperative and postoperative visual acuitycomparing phototherapeutic keratectomy andmechanical collagen crosslinking

PTK Mechanical

*MRSE 1.68 � 0.80 0.26 � 0.90*Cylinder 0.53 � 0.28 0.00 � 0.18Sphere 0.27 � 0.60 0.045 � 0.19Lines of improvement 0.33 � 0.82 �0.58 � 0.45Epithelial thickness 43.5 � 7.64 33.9 � 6.36

MRSE, manifest refraction spherical equivalent; PTK, phototherapeutic keratectomy.*Indicates statistically significant difference between the groups (p � 0.05).

immediately after epithelial removal in both the PTK and

346 CAN J OPHTHALMOL—VOL. 47, NO. 4, AUGUST 2012

the mechanical groups was 43.5 � 7.64 (range, 1 to 104)and 33.9 � 6.36 (range, 4 to 118), respectively. Thischange was not statistically significant (p � 0.134; paired ttest), but the trend was that a 50 �m transepithelial PTKremoved more corneal tissue than did the mechanicalmethod, as expected. Table 2 shows these results.

At the first follow-up visit, 1-week postoperatively, allpatients had complete epithelial resolution.

In the early, 1-month postoperative period, 8 eyes lost 1 or2 lines of CDVA; 4 eyes lost lines in each group. No eyes lostmore than 2 lines. Statistically, there was no difference be-tween the groups (p � 0.05). In addition, no eyes in the PTKgroup and 1 eye (1.25 D) in the mechanical group gainedmore than 1 diopter of cylinder after the CXL procedure.

DISCUSSION

The efficacy of CXL in halting the progression ofkeratoconus has been shown in previous studies.15

Studies have also shown how transepithelial PTK usesan excimer laser to smooth the anterior, irregular corneaas well as to remove the epithelium.16,17 In our 17 pa-tients who received PTK CXL, 50 �m PTK was usednot only to remove the epithelium but to also ablate theapex of the cone where the epithelium is thinner. At the1-week mark, all patients had epithelial resolution. Cor-neal epithelial thickness is normally approximately 50 �mbut is thinner in the keratoconic eye.18 Our results indicatethat subjects who received laser epithelial removal had atrend toward a greater change in epithelial thickness thandid subjects who received brush removal. Furthermore, theamount of change in both groups was as expected; a meanchange of 43.5 �m for the 50 �m PTK group and a meanchange of 33.9 �m for the mechanical group. Becausekeratoconic eyes have thinner epithelia, the laser must haveremoved stroma in addition to epithelium in the PTKgroup. Therefore, essentially a superficial keratectomy wasperformed, reducing astigmatism and smoothing out thecornea, as shown by our results.

The purpose of this study was to report the preliminaryresults of comparing the techniques of mechanical andPTK epithelial removal. There are some limitations to thisstudy because of its retrospective nature. To allow for avalid comparison, patients in the mechanical group werematched to patients in the PTK group on the parameters ofpachymetry and keratometry prior to being consecutivelyselected. We are thus not able to report findings that com-pare keratometry and pachymetry because of the selectionbias. Furthermore, MMC was used in the PTK group but

Table 2—Variables comparing PTK and mechanical CXL

Preoperative Postoperative

PTK 0.576 � 0.070 0.608 � 0.069Mechanical CXL 0.696 � 0.064 0.672 � 0.073

CXL, collagen crosslinking; PTK, phototherapeutic keratectomy.

Phototherapeutic keratectomy for keratoconus—Kapasi et al.

not in the mechanical group. While studying an enucle-ated eye 24 hours after CXL in vivo, Wollensak noted anunremarkable Bowman’s membrane but noticed a treat-ment effect in the anterior stroma.19 It is possible thatBowman’s membrane may act as a barrier to stromal ribo-flavin absorption in the mechanical procedure, but we areunable to comment because we did not study riboflavinabsorption. Finally, patients in this study all had centralcones as identified by Scheimpflug imaging.

Nevertheless, our results indicate that PTK CXL may besuperior to CXL in mechanical epithelial removal because itreduces refractive error in qualified patients and has the addedbenefit of smoothing out the cornea. The mean change inMRSE and astigmatism preoperatively to 1 month postoper-atively was significantly better in the PTK group. Althoughnot statistically significant, there was also a trend for PTKCXL patients to have better visual outcomes that were iden-tifiable as early as 1 month postoperatively.

A future prospective study would be better at comparingthese 2 treatment arms by having longer follow-up, subjectrandomization, data on both central and eccentric cones,the ability to control for MMC use, and the elimination ofselection bias. A study with more patients and varying PTKdepth would perhaps result in a significant difference in thechange in pachymetry, before and after epithelial removal.This preliminary study served to lay the groundwork for amore robust, prospective study but also highlighted the po-tential benefits of PTK CXL early in the postoperative period.

Disclosure: The authors have no proprietary or commercial interestin the materials discussed in this article.

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