Many people with refractive error who have visual aberrations seek a surgical option because they are inconvenienced by wearing glasses or are intolerant of contact lenses. Since the early days of laser vision correction, visual outcomes and safety profiles have improved significantly. Success is no longer correlated with 20/20 vision but rather with the percentage of patients who see better than 20/20. LASIK continues to be a popular option, not only because visual recovery is rapid, but also because the procedure and recovery period are relatively painless. Most patients return to work on the first postoperative day.
Despite the economic recession, the advent of femtosecond lasers for creating the flap, and the advantages of LASIK, many refractive surgeons continue to offer surface ablation.1,2 In fact, the proportion of patients treated with surface ablation increased from 2007 to 2009.3 As will be discussed in this installment of Peer Review, evidence suggests that, despite a longer visual recovery period than with LASIK and discomfort in the early postoperative period, the long-term visual results of excimer laser surface ablation are comparable with those of LASIK.
In the first of a two-part series on surface ablation, David O’Brart, MD, FRCS, FRCOphth, focuses on how these excimer laser-based procedures compare, the use of mitomycin C (MMC), and surgical techniques for epithelial removal. I hope you enjoy this installment of Peer Review, and I encourage you to seek out and review the cited articles in their entirety at your convenience.
LASIK VERSUS PRK
In the early days of laser keratorefractive surgery, with small optical treatment zones and iris diaphragm technology, PRK was associated with iatrogenic haze and poor predictability, especially for the correction of high myopia.4 By removing the epithelial trigger for corneal stromal wound healing, LASIK afforded greater predictability and far less risk of iatrogenic haze.5 With the development of wider optical treatment zones,6 smoother ablation profiles with flying-spot technology, and the pharmacologic modulation of wound healing using adjunctive medications such as MMC,7 however, the long-term outcomes of modern excimer laser-based surface treatments appear to be comparable to those of LASIK.8-12
In recent years, several randomized, prospective, clinical studies comparing PRK and LASIK using modern laser technology and techniques have been published.8-10 Wallau and Campos,8 in a study comparing myopic PRK with MMC and LASIK, reported significantly better UCVA and BCVA, better contrast sensitivity, and fewer higher-order aberrations in PRK-treated eyes compared with LASIK-treated eyes. Similarly, in a study comparing wavefront-guided myopic PRK and LASIK, Moshirfar et al9 found the two procedures to have similar efficacy, predictability, and safety and to achieve similar contrast sensitivity, although PRK produced significantly fewer higher-order aberrations.When Manche and Haw10 compared the safety and efficacy of wavefront-guided LASIK versus PRK, they found no difference between the two procedures 3 months postoperatively, and they did not report haze in the PRK-treated eyes.
Regarding hyperopic corrections, clinical studies using wide-diameter (7-mm) ablations with modern laser platforms have achieved excellent outcomes despite significant initial overcorrection and delayed (up to 6 months) postoperative refractive stabilization.11 There is a paucity of randomized, controlled trials that compare hyperopic LASIK with hyperopic PRK; nonrandomized trials, however, have demonstrated comparable efficacy.12
ADJUNCTIVE USE OF MMC
MMC is a DNA alkylating agent derived from Streptomyces caepitosus. The agent inhibits DNA and RNA replication in rapidly dividing cells such as fibroblasts, thereby suppressing wound healing. Talamo13 first suggested the adjunctive use of MMC in PRK more than 20 years ago. Surgeons’ renewed interest in surface ablation over the past decade has led to the routine implementation of MMC, especially for high corrections and in eyes at risk of developing iatrogenic haze (ie, those that have undergone previous corneal surgery).
In a prospective, randomized, double-masked, pairedeye study of treatments between -6.50 and -10.00 D, Leccisotti14 reported significantly less haze in eyes treated with MMC 0.2 mg/mL for 45 seconds. The overcorrection rate in this study, however, was approximately 6%. Similarly, Wallau and Campos8 reported better outcomes for PRK with MMC than LASIK, with no haze observed in eyes treated with PRK and MMC. A recent meta-analysis of clinical outcomes comparing surface ablation with and without MMC 0.02% showed that the agent reduced haze, although the advantages of using MMC in conjunction with LASEK were unclear.15
There is some dispute regarding the optimal concentration of MMC and perioperative application time. In a retrospective study, Thornton et al,16 using multivariable analysis, found significantly less haze in eyes that underwent myopic corrections greater than -6.00 D and ablations deeper than 75 μm when they were treated with MMC 0.02% versus 0.002%. Virasch et al17 found no statistically significant difference in BCVA or haze scores with the administration of MMC 0.02% for 12 seconds compared with longer application times of 60 and 120 seconds. In contrast, in an ex vivo study of human eyes obtained from an eye bank, Rajan et al18 found that the use of MMC 0.02% for 60 seconds resulted in optimal modulation of healing that was characterized by reduced keratocytic activation with normal epithelial differentiation. Undoubtedly, there is a need for randomized controlled studies in this area to optimize MMC application.
The use of MMC in keratorefractive procedures is not without controversy. Corneal and scleral melting have been reported, both within months and many years after the agent’s use in pterygium surgery.19 Many refractive surgeons have concerns regarding potential unknown long-term complications of MMC. Reports of delayed epithelial wound healing without any consequent induction of iatrogenic haze with MMC 0.02%20 are inconsistent with some investigators’ findings.14 In a review of five studies by Roh and Funderburgh,21 three demonstrated that MMC had no effect on corneal endothelial density, but two found significant cellular loss after MMC application. A prospective study that evaluated MMC 0.02% applied for 40 seconds showed no change in central endothelial counts 6 months postoperatively.22 In a randomized, bilateral study using in vivo confocal microscopy, Gambato et al23,24 found no changes 5 years postoperatively with the intraoperative use of MMC 0.02% in endothelial cell counts; epithelial thickness; keratocytic density; the number of corneal nerve fibers; or nerve beadings, branching, or tortuosity. Studies with large series and longer follow-up are needed to determine the influence of MMC on the cornea and endothelium after PRK. Although the literature appears to support MMC in eyes at risk of the development of iatrogenic haze, patients should be informed preoperatively of the possibility of rare and long-term complications.
TECHNIQUES FOR EPITHELIAL REMOVAL
Several methods have been proposed for the removal of the epithelium during surface ablation (eg, mechanically with blades and brushes, with alcohol, with modified microkeratomes, and with the excimer laser). There is no clear evidence, however, as to which approach is best.
Einollahi et al25 compared mechanical versus alcoholassisted epithelial debridement during PRK in a randomized clinical trial. The investigators reported slower epithelial healing time and reduced retroablation stromal keratocytic density with mechanical debridement. In a meta-analysis of the clinical outcomes of LASEK and PRK in myopic eyes, Zhao et al26 reported that LASEK-treated eyes demonstrated no significant benefits compared with PRK-treated eyes in regard to clinical outcomes. The investigators also observed less corneal haze in LASEK-treated eyes 1 to 3 months postoperatively. In a large, randomized, controlled study, Ghoreishi et al27 found comparable results between alcohol-assisted and mechanical epithelial removal in PRK.
The use of specially adapted microkeratomes for epithelial removal (epi-LASIK) has been advocated,28 but clinical results with these instruments are conflicting. When Sia et al compared visual outcomes after epi- LASIK and PRK, they reported superior refractive efficacy and stability but slower reepithelialization with the former.29 For myopic corrections, Teus et al reported that, when compared with epi-LASEK, LASEK demonstrated greater safety and efficacy and was associated with faster visual rehabilitation.30 Hondur et al31 found comparable results between epi-LASIK and LASEK 12 months postoperatively.
Transepithelial PRK has been shown to result in less pain and haze compared with alcohol-assisted PRK, but the visual outcomes of the two techniques are similar.32 Similarly, Aslanides et al33 reported lower pain scores, faster epithelial healing, and less haze 6 months postoperatively with an all-laser technique. In contrast, Luger et al34 found no difference in efficacy or safety between the two techniques.
Although the results of these studies provide conflicting data, they all report excellent visual and refractive outcomes, and there appears to be little difference in the long-term results of epithelial removal techniques.25-34 Further prospective, randomized clinical studies are warranted, but at the present time the technique for epithelial removal is a matter of the surgeon’s preference.
Allon Barsam, MD, MA, FRCOphth, is a consultant ophthalmic surgeon at Luton & Dunstable University, The Western Eye Hospital, Imperial College Healthcare NHS Trust, and Focus Clinics in London. Dr. Barsam may be reached at e-mail: email@example.com.
David P. S. O’Brart, MD, FRCS, FRCOphth, is a consultant ophthalmologist in the Department of Ophthalmology at St. Thomas’ Hospital, London. Dr. O’Brart may be reached at tel: +44 1702 586656; e-mail: firstname.lastname@example.org.
- Schmack I, Auffarth GU, Epstein D, Holzer MP. Refractive surgery trends and practice style changes in Germany over a three-year period. J Refract Surg. 2010;26:202-208.
- Stanley PF, Tanzer DJ, Schallhorn SC. Laser refractive surgery in the United States Navy. Curr Opin Ophthalmol. 2008;19(4):321-324.
- Kuo IC. Trends in refractive surgery at an academic center: 2007-2009. BMC Ophthalmol. 2011;14:11:11. 4. O’Brart DP, Gartry DS, Lohmann CP, et al. Excimer laser photorefractive keratectomy for myopia: comparison of 4.00- and 5.00-millimeter ablation zones. J Refract Corneal Surg. 1994;10(2):87-94.
- Pallikaris IG, Siganos DS. Laser in situ keratomileusis to treat myopia: early experience. J Cataract Refract Surg. 1997;23(1):39-49.
- O’Brart DP, Corbett MC, Lohmann CP, et al. The effects of ablation diameter on the outcome of excimer laser photorefractive keratectomy. A prospective, randomized, double-blind study. Arch Ophthalmol. 1995;113(4):438-443.
- Shalaby A, Kaye GB, Gimbel HV. Mitomycin C in photorefractive keratectomy. J Refract Surg. 2009;25(1 suppl):S93-S97.
- Wallau AD, Campos M. One-year outcomes of a bilateral randomised prospective clinical trial comparing PRK with mitomycin C and LASIK. Br J Ophthalmol. 2009;93(12):1634-1638.
- Moshirfar M, Schliesser JA, Chang JC, et al. Visual outcomes after wavefront-guided photorefractive keratectomy and wavefront-guided laser in situ keratomileusis: prospective comparison. J Cataract Refract Surg. 2010;36(8):1336-1343.
- Manche EE, Haw WW. Wavefront-guided laser in situ keratomileusis (LASIK) versus wavefront-guided photorefractive keratectomy (PRK): a prospective randomized eye-to-eye comparison (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2011;109:201-220.
- O’Brart, DP, Mellington F, Jones S, Marshall J. Laser epithelial keratomileusis for the correction of hyperopia using a 7.0-mm optical zone with the Schwind ESIRIS laser. J Refract Surg. 2007;23(4):343-354.
- Settas G, Settas C, Minos E, Yeung IY. Photorefractive keratectomy (PRK) versus laser assisted in situ keratomileusis (LASIK) for hyperopia correction. Cochrane Database Syst Rev. 2012;6:CD007112.
- 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(8):1141-1146.
- Leccisotti A. Mitomycin C in photorefractive keratectomy: effect on epithelialization and predictability. Cornea. 2008;27(3):288-291.
- Chen SH, Feng YF, Stojanovic A, Wang QM. Meta-analysis of clinical outcomes comparing surface ablation for correction of myopia with and without 0.02% mitomycin C. J Refract Surg. 2011;27(7):530-541.
- Thornton I, Xu M, Krueger RR. Comparison of standard (0.02%) and low dose (0.002%) mitomycin C in the prevention of corneal haze following surface ablation for myopia. J Refract Surg. 2008;24(1):S68-76.
- Virasch VV, Majmudar PA, Epstein RJ, et al. Reduced application time for prophylactic mitomycin C in photorefractive keratectomy. Ophthalmology. 2010;117(5):885-889.
- Rajan MS, O’Brart DP, Patmore A, Marshall J. Cellular effects of mitomycin-C on human corneas after photorefractive keratectomy. J Cataract Refract Surg. 2006;32(10):1741-1747.
- Ti SE, Tan DT. Tectonic corneal lamellar grafting for severe scleral melting after pterygium surgery. Ophthalmology. 2003;110(6):1126-1136.
- Kremer I, Ehrenberg M, Levinger S. Delayed epithelial healing following photorefractive keratectomy with mitomycin C treatment. Acta Ophthalmol. 2012;90(3):271-276.
- Roh DS, Funderburgh JL. Impact on the corneal endothelium of mitomycin C during photorefractive keratectomy. J Refract Surg. 2009;25(10):894-897.
- Zare M, Jafarinasab MR, Feizi S, Zamani M. The effect of mitomycin-C on corneal endothelial cells after photorefractive keratectomy. J Ophthalmic Vis Res. 2011;6(1):8-12.
- Gambato C, Miotto S, Cortese M, et al. Mitomycin C-assisted photorefractive keratectomy in high myopia: a long-term safety study. Cornea. 2011;30(6):641-645.
- Midena E, Gambato C, Miotto S, et al. Long-term effects on corneal keratocytes of mitomycin C during photorefractive keratectomy: a randomized contralateral eye confocal microscopy study. J Refract Surg. 2007;23(9 suppl):S1011-S1014.
- Einollahi B, Baradaran-Rafii A, Rezaei-Kanavi M, et al. Mechanical versus alcohol-assisted epithelial debridement during photorefractive keratectomy: a confocal microscopic clinical trial. J Refract Surg. 2011;27(12):887-893.
- Zhao LQ, Wei RL, Cheng JW, et al. Meta-analysis: clinical outcomes of laser-assisted subepithelial keratectomy and photorefractive keratectomy in myopia. Ophthalmology. 2010;117(10):1912-1922.
- Ghoreishi M, Attarzadeh H, Tavakoli M, et al. Alcohol-assisted versus mechanical epithelium removal in photorefractive keratectomy. J Ophthalmic Vis Res. 2010;5(4):223-227.
- Winkler von Mohrenfels C, Khoramnia R, Maier M, Lohmann CP. Epi-LASIK with mitomycin C. Eur J Ophthalmol. 2010;20(1):55-61.
- Sia RK, Coe CD, Edwards JD, et al. Visual outcomes after Epi-LASIK and PRK for low and moderate myopia. J Refract Surg. 2012;28(1):65-71.
- Teus MA, de Benito-Llopis L, García-González M. Comparison of visual results between laser-assisted subepithelial keratectomy and epipolis laser in situ keratomileusis to correct myopia and myopic astigmatism. Am J Ophthalmol. 2008;146(3):357-362.
- Hondur A, Bilgihan K, Hasanreisoglu B. A prospective bilateral comparison of epi-LASIK and LASEK for myopia. J Refract Surg. 2008;24(9):928-934.
- Fadlallah A, Fahed D, Khalil K, et al. Transepithelial photorefractive keratectomy: clinical results. J Cataract Refract Surg. 2011;37(10):1852-1857.
- Aslanides IM, Padroni S, Arba Mosquera S, et al. Comparison of single-step reverse transepithelial all-surface laser ablation (ASLA) to alcohol-assisted photorefractive keratectomy. Clin Ophthalmol. 2012;6:973-980.
- Luger MH, Ewering T, Arba-Mosquera S. Consecutive myopia correction with transepithelial versus alcohol-assisted photorefractive keratectomy in contralateral eyes: one-year results. J Cataract Refract Surg. 2012;38(8):1414-1423.