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CLINICAL SCIENCE

Mechanical Supercial Keratectomy for Corneal Haze After Photorefractive Keratectomy With Mitomycin C and Extended Wear Contact Lens
Hamid Khakshoor, MD, Mehran Zarei-Ghanavati, MD, and Ladan Saffarian, MD

Purpose: To evaluate the clinical results of a mechanical


keratectomy with mitomycin C (MMC) and extended wear contact lens (EWCL) for the treatment of corneal haze after photorefractive keratectomy (PRK) of high myopia.

Key Words: photorefractive keratectomy, corneal haze, mechanical keratectomy, scraping, mitomycin C, extended wear contact lens (Cornea 2011;30:117120)

Setting: Eye Research Center, Khatam-al-Anbia Eye Hospital, Mashhad University of Medical Sciences, Iran. Methods: In a retrospective interventional case series, we enrolled 15 eyes of 9 patients who previously underwent PRK for high myopia and developed corneal haze and regression. Mechanical removal of corneal haze was done by using a surgical blade number 15. Then, MMC (0.02%) was used for 2 minutes. An EWCL was applied for 1 month. The main outcome measures were uncorrected visual acuity, best-corrected visual acuity, spherical equivalent (SE), and corneal haze grade. All patients were followed for a minimum of 6 months. Results: The mean age of the patients was 25.66 6 7.03 years;
7 patients were men and 2 patients were women. The mean bestcorrected visual acuity before supercial keratectomy was 20/80 (range, 20/20020/50) and improved to 20/20 after treatment (P , 0.05). Thirteen eyes (86.6%) achieved an uncorrected visual acuity of at least 20/40. The mean preoperative SE was 3.91 6 1.30, and the mean nal postoperative SE was 20.85 6 1.19 (P , 0.05). Eight eyes (53%) were within 1 diopter of emmetropia. Corneal haze in all patients declined to a trace haze or complete clearness. No recurrence occurred during the mean follow-up time of 12 months.

Conclusions: Supercial keratectomy with MMC and EWCLs is effective in reducing persistent and refractory corneal haze after PRK.

xcimer laser photorefractive keratectomy (PRK) was rst introduced in 1988.1 Although it has less effect on the biomechanical integrity of the cornea compared with laser in situ keratomileusis, corneal haze that causes optical scattering and visual loss remains a major disadvantage of PRK.2 Moreover, it is associated with myopic regression.3 Clinically signicant corneal haze after PRK has been seen in nearly 5% of patients.2,4 Corneal haze typically appears within the rst few weeks after PRK (early onset) and increases in intensity at 12 months and gradually disappears during the next 612 months.5,6 The late-onset corneal haze develops at least 3 months or more after PRK.7,8 The exact pathological mechanisms of corneal haze remain unclear. Several studies have demonstrated that a single application of topical mitomycin C (MMC) is effective in preventing corneal haze after PRK.911 Surgical options available to treat corneal haze after failure of topical corticosteroids include phototherapeutic keratectomy (PTK) and the combination of mechanical scraping with MMC. The objective of this article is to evaluate the efcacy and safety of combining supercial keratectomy (SK) with topical MMC to treat corneal haze after PRK.

MATERIALS AND METHODS


Received for publication May 5, 2009; revision received January 15, 2010; accepted January 24, 2010. From the *Khatam-al-Anbia Eye Hospital, Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Khorasan, Iran; and Islamic Azad University of Mashhad, Mashhad, Iran. Supported by Eye Research Center, Mashhad University of Medical Sciences, Iran. Presented at the 2009 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting, April 38, 2009, San Francisco, CA. No author has a nancial or proprietary interest in any material or method mentioned. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journals Web site (www.corneajrnl.com). Reprints: Hamid Khakshoor, Eye Research Center, Khatam-al-Anbia Eye Hospital, Abootaleb Boulevard, Mashhad, Khorasan 91869-13556, Iran (e-mail: hkhakshoor@yahoo.com). Copyright 2011 by Lippincott Williams & Wilkins

Selection of Patients
Between April 2004 and August 2006, we conducted a retrospective noncomparative study of 9 consecutive patients with corneal haze at least 1 year after PRK. PRK was performed using a Technolas 217z excimer laser system (Bausch & Lomb). All procedures were performed at the Navid Didegan Eye Center, with the exception of 2 patients who were referred from other centers. All patients were treated for myopia. MMC was used intraoperatively for varying times of exposure, which was dependent on the degree of myopia. No patient had any systemic risk factors for corneal haze. Corneal haze initially appeared in the rst few weeks (early onset) and was present after at least 1 year. All patients were treated with topical betamethasone without signicant response and had corneal haze ranging from grade 2 to grade 4. All patients had
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best-corrected visual acuity (BCVA) below 20/40 and signicant optical symptoms such as halo, glare, and ghost image.

TABLE 1. Preoperative Characteristics of 9 Patients (15 Eyes) With Corneal Haze


Age Number (Yrs) 1 2 3 4 5 6 7 8 9 39 24 19 22 19 29 34 25 20 Sex Male Male MSE Corneal Haze BCVA Eye (Before SK) (Before SK) (Before SK) 25.25 23 23.25 22.25 25.25 24.75 24.75 21.75 21.75 24.25 25.75 23.25 24 25 24.5 3 2 2 2 2 3 3 3 3 3 3 3 4 3 3 20/125 20/80 20/80 20/50 20/50 20/200 20/160 20/50 20/50 20/125 20/125 20/160 20/250 20/120 20/160

Clinical Evaluations
Detailed ophthalmological examinations were done for all patients including a slit-lamp examination, tonometery, indirect fundoscopy, and pachymetry. Uncorrected visual acuity (UCVA) and BCVA were determined using Early Treatment Diabetic Retinopathy Study visual acuity charts (ETDRS). Corneal scars were graded using a slit-lamp microscope according to the grading system of Fantes et al.12 The systematic denitions are as follows: grade 0, totally clear; grade 0.5, trace or faint corneal haze seen only by indirect broad tangential illumination; grade 1, minimal haze seen with difculty using direct and diffuse illumination; grade 2, mild haze that is easily visible with direct focal slit illumination; grade 3, moderately dense opacity that partially obscures the details of the iris; and grade 4, severely dense opacity that completely obscures the details of intraocular structures.

OD OD OS Female OD Male OS Male OD OS Female OD OS Male OD OS Male OD OS Male OD OS

Surgical Technique
Informed consent was obtained from all patients, and all surgeries were performed by a single surgeon (H. K.). Under topical anesthesia, mechanical removal of the corneal epithelium and stromal haziness was performed with a surgical blade (number 15) until complete smoothness and clearness of the underlying stroma were achieved. A sponge soaked with MMC (0.02%) was directly applied over the exposed cornea for 1 minute. The cornea and conjunctival sac were irrigated with 20 cc balanced salt solution. MMC was applied again for 1 minute and then washed out. An extended wear night and day bandage contact lens (CIBA Vision) was applied for 1 month (see Video, Supplemental Digital Content 1, http://links.lww.com/ICO/A11). The postoperative therapeutic regime included topical ciprooxacin and betamethasone (4 times a day) for the rst week. Afterward, ciprooxacin drops were applied twice a day until bandage contact lens was removed. Betamethasone was replaced with uorometholone given 4 times daily for 1 month and then tapered by 1 drop every month over the following 3 months until cessation. Follow-up examinations were done on postoperative days 1, 2, 4, and 7. After the rst week, examinations were done weekly until the end of the rst month and then at 3, 6, and 12 months after surgery.

MSE, manifest spherical equivalent.

keratitis or other lens-related complications were present (Table 1). The mean BCVA before SK was 20/80 and ranged from 20/20020/50. Three patients (4 eyes) had grade 2 corneal haze, 1 patient (1 eye) had grade 4, and 5 patients (10 eyes) had grade 3 (Fig. 1). The mean spherical equivalent showing signicant regression was 23.91 6 1.30 (Table 1). The mean BCVA after treatment improved to 20/20 and ranged from 20/2520/16 (P , 0.05). The mean spherical equivalent was changed to 20.85 6 1.19 (P , 0.05). Two eyes were overcorrected for more than +0.5 diopter (D), but more than 1 D of myopia was seen in 6 eyes, whereas only 8 eyes (53%) were within 1 D of emmetropia (Fig. 2). Thirteen eyes (86.6%) achieved UCVA of at least 20/40 (range from 20/8020/16). Corneal haze after scraping (grade range, 00.5) differed from that before scraping (grade range, 24) (P , 0.05) (Fig. 3). It was totally eliminated in 7 eyes (46.6%) and

Statistical Analyses
The Wilcoxon signed rank and x2 tests were used for statistical analyses and performed using SPSS software (SPSS, Inc). The results are expressed as mean 6 SD. A P value less than 0.05 was considered statistically signicant.

RESULTS
This case series included 9 patients (15 eyes of 7 men and 2 women). The mean age of the patients was 25.66 6 7.03 years. The mean follow-up time after keratectomy was 12.11 6 3.25 months. Supercial keratectomy was performed after 2 years of haze formation in 3 patients (cases 2, 4, and 9). Epithelialization was complete by the fourth day. No bacterial

FIGURE 1. Patient number 6: A 29-year-old woman who had undergone PRK 13 months before participating in the study. BCVA was 20/50. q 2011 Lippincott Williams & Wilkins

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Mechanical Keratectomy for Corneal Haze

TABLE 2. Postoperative Results of Superficial Keratectomy in Eyes With Corneal Haze


MSE Corneal Haze BCVA UCVA Last F/U Number (Last F/U) (Last F/U) (Last F/U) (Last F/U) (Mo) 1 2 3 4 5 6 7 8 9 21.5 22.75 21.25 0.25 20.5 21.25 20.75 20.25 0.75 20.75 20.5 20.25 1.25 22.25 23 0.5 0.5 0 0 0 0.5 0 0 0.5 0 0.5 0 0 0.5 0.5 20/25 20/20 20/16 20/16 20/20 20/20 20/20 20/20 20/20 20/20 20/16 20/16 20/16 20/20 20/20 20/40 20/80 20/40 20/25 20/30 20/25 20/20 20/20 20/25 20/25 20/25 20/16 20/40 20/40 20/50 14 11 11 12 19 13 13 9 9 8 8 10 10 13 13

FIGURE 2. Final spherical equivalent refractive outcomes after SK. Eight eyes (53%) were within 1 D of emmetropia.

signicantly reduced in others (Table 2). No patients had recurrence of corneal haze during follow-up.

DISCUSSION
Supercial keratectomy, as demonstrated here, is a safe and effective method for treating corneal haze after PRK. Most patients achieved UCVA of 20/40 or better. The measured increase in BCVA was $ 3 lines in all eyes measured, with the exception of one. Additionally, all patients reported improvement of symptoms regarding optical aberrations. The procedure decreased regression but usually led to undercorrection of myopia. Corneal haze was signicantly reduced and stabilized during follow-up without side effects. When the treatment of corneal haze with topical corticosteroids is unsuccessful, there are 2 alternative therapeutic modalities, PTK and SK. Porges et al13 studied the use of PTK with MMC for treatment of corneal haze. They reported that

FIGURE 3. A 29-year-old woman who had UCVA of 20/25 and trace corneal haze at 9 months after supercial keratectomy. q 2011 Lippincott Williams & Wilkins

only 37.5% of patients were within 1 D of emmetropia and the mean BCVA after treatment was 7/10. These results demonstrate that PTK leads to less predictable and regular stromal removal than mechanical keratectomy. PTK often results in overcorrection of myopia because refraction is imprecise in the presence of corneal haze. Moreover, the corneal surface is uneven after ablation because of presence of brous tissue in the corneal stroma. Two previous studies that used mechanical keratectomy with MMC to treat corneal haze reported favorable results.14,15 Loewenstein et al14 showed that only 38% of patients had UCVA of 20/30 or better. In our study, 53% of eyes had UCVA of at least 20/30. Vigo et al15 recommend that scraping should be done 810 months after PRK because mechanical removal would be difcult after a longer period of haze formation. They did not publish nal BCVA of their patients. We performed supercial keratectomy after 2 years of haze formation in 3 of our patients. Although surgery is more time consuming in these patients with old corneal haze, the results were comparable with that achieved in other patients. Talamo et al16 rst used MMC to treat corneal wounds after excimer laser surgery. Although prophylactic application of MMC reduces corneal haze, this complication still occurs after PRK.17 Moreover, previous studies13,15 showed that corneal haze returned to some extent after treatment with MMC. We used therapeutic bandage contact lenses for 1 month with all patients. We noticed that extended wear contact lenses (EWCLs) might provide benet with regard to preventing corneal haze. This is based on an incidental nding in 1 patient who underwent PRK with MMC for correction of myopia (26.5) of both eyes. After 1 month, the patient presented with corneal haze in the right eye (grade 3) where the contact lens had been lost. No evidence of corneal haze was observed in the left eye where the contact lens remained in place. It is possible that the benet observed using EWCLs is from their effects in posterior distribution and reduction of stromal keratocytes. Using confocal microscopy, Efron et al18 observed a loss of
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keratocytes after use of EWCLs and hypothesized that it may involve the mechanical effect of contact lenses. Other studies showed redistribution of keratocytes after using EWCLs,19 although some discrepancies exist between these studies.20 In addition, multiple studies show that contact lenses inhibit polymorphonuclear leukocyte.21,22 Mller-Pedersen et al8 showed that increased light reection of keratocytes after PRK greatly contributes to the corneal haze formation. Jester et al23 proposed that the optical characteristics of keratocytes after injury are related to a change in protein expression. Through mechanical effects on the corneal surface, contact lenses may prevent activation of keratocytes that occurs after PRK.24 Vinciguerra et al25 noted that smoothing ablated surfaces after PRK decreased the incidence of corneal haze. We think that using EWCL after SK may provide a more even surface by remodeling the corneal stroma, which leads to a reduction of corneal haze recurrence after SK. A major limitation in our study is the lack of a well-dened control group to compare the effect of contact lenses. Furthermore, more highly controlled case studies are required to investigate the benet of EWCL in the treatment of corneal haze. In conclusion, supercial keratectomy with MMC and EWCLs is an effective treatment in reducing persistent corneal haze after PRK. REFERENCES
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8. Lipshitz I, Loewenstein A, Varssano D, et al. Late onset corneal haze after photorefractive keratectomy for moderate and high myopia. Ophthalmology. 1997;104:369373. 9. Majmudar PA, Forstot SL, Dennis RF, et al. Topical mitomycin-C for subepithelial brosis after refractive corneal surgery. Ophthalmology. 2000;107:8994. 10. Morales AJ, Zadok D, Mora-Retana R, et al. Intraoperative mitomycin and corneal endothelium after photorefractive keratectomy. Am J Ophthalmol. 2006;142:400404. 11. Xu H, Liu S, Xia X, et al. Mitomycin C reduces haze formation in rabbits after excimer laser photorefractive keratectomy. J Refract Surg. 2001;17: 342349. 12. Fantes FE, Hanna KD, Waring GO III, et al. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch Ophthalmol. 1990;108:665675. 13. Porges Y, Ben-Haim O, Hirsh A, et al. Phototherapeutic keratectomy with mitomycin C for corneal haze following photorefractive keratectomy for myopia. J Refract Surg. 2003;19:4043. 14. Loewenstein A, Lipshitz I, Lazar M. Scraping of epithelium for treatment of undercorrection and haze after photorefractive keratectomy. J Refract Corneal Surg. 1994;10(Suppl 2):S274S276. 15. Vigo L, Scandola E, Carones F. Scraping and mitomycin C to treat haze and regression after photorefractive keratectomy for myopia. J Refract Surg. 2003;19:449454. 16. Talamo JH, Gollamudi S, Green WR, et al. Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids. Arch Ophthalmol. 1991;109:11411146. 17. Lee DH, Chung HS, Jeon YC, et al. Photorefractive keratectomy with intraoperative mitomycin-C application. J Cataract Refract Surg. 2005; 31:22932298. 18. Efron N, Perez-Gomez I, Morgan PB. Confocal microscopic observations of stromal keratocytes during extended contact lens wear. Clin Exp Optom. 2002;85:156160. 19. Jalbert I, Stapleton F. Effect of lens wear on corneal stroma: preliminary ndings. Aust N Z J Ophthalmol. 1999;27:211213. 20. Patel SV, McLaren JW, Hodge DO, et al. Confocal microscopy in vivo in corneas of long-term contact lens wearers. Invest Ophthalmol Vis Sci. 2002;43:9951003. 21. Stapleton F, Willcox MD, Sansey N, et al. Ocular microbiota and polymorphonuclear leucocyte recruitment during overnight contact lens wear. Aust N Z J Ophthalmol. 1997;25(Suppl 1):S33S35. 22. Thakur A, Willcox MD. Cytokine and lipid inammatory mediator prole of human tears during contact lens associated inammatory diseases. Exp Eye Res. 1998;67:919. 23. Jester JV, Moller-Pedersen T, Huang J, et al. The cellular basis of corneal transparency: evidence for corneal crystallins. J Cell Sci. 1999;112: 613622. 24. Efron N. Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope. Prog Retin Eye Res. 2007;26: 398436. 25. Vinciguerra P, Azzolini M, Airaghi P, et al. Effect of decreasing surface and interface irregularities after photorefractive keratectomy and laser in situ keratomileusis on optical and functional outcomes. J Refract Surg. 1998;14(Suppl 2):S199S203.

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