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215 Original Article The Efficacy, Predictability, and Safety of Epi-Lasik for The Correction of Myopia Faisal M. Tobaigy, MD; Leonard Ang, MD, Phd; Dimitri T. Azar, MD Abstract Purpose. To report the refractive and visual results of epithelial laser in situ keratomileusis (Epi-LASIK) for the treatment of myopia. Design. Retrospective non-comparative consecutive case series. Methods. Sixty nine eyes of 40 patients had Epi-LASIK for the treatment of low myopia or myopic astigmatism. All epithelial separations were performed with the Visijet/Gebauer microkeratome. Primary outcome variables included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, epithelization time, pain, haze and complications. Results. Preoperatively, the mean spherical equivalent (SE) was -3.9 diopters (D) ± 1.6 D (range -.75 to -7.00 D) and the mean LogMAR BSCVA was 0.0131±0.041 (range -0.10 to 0.12). On the final visit, the mean SE was 0.27+0.53D (range -2.50 to 0.50D), the mean logMAR UCVA was -0.079±0.13 (range -0.48 to 0.12) and the mean LogMAR BSCVA was 0.0039 ± 0.053 (range -0.18 to 0.1). 95.1% of eyes achieved a vision of 20/40 or better, and 70.5% achieved a vision of 20/25 or better. 73.8% and 95.1% of eyes were within +0.5D and +1.0D, respectively. Complete epithelialization occured in 6.2 ±1.4 days (range 3 to 8 days); 93.4% of eyes had clear corneas or only trace haze at the final postoperative visit; 94.7% of eyes had no or minimal pain. Conclusions. Epi-LASIK is a safe, effective and predictable method for the treatment of low to moderate myopia and myopic astigmatism. Key Words: Epi-lasik, epithelial laser in situ keratomileusis W ith the rapid evolution of refractive surgery and availability of wide range of treatment modalities, the surgeon can select the right procedure for the patient according to his or her needs and limits. In the early nineties, PRK was the most commonly performed refractive surgery and continued to be popular until the introduction of LASIK. Each procedure has its own From the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and the Schepens Research Institute, Harvard Medical School, Boston, Massachusetts, United States of America. Correspondence to Faisal M. Al-Tobaigy, MD, Assistant Professor of Ophthalmology, College of Medicine, Jazan University. PO Box 114, Jazan, Kingdom of Saudi Arabia. Telephone: 00966-07-3217800; Fax: 00966-073217800; E-mail: [email protected] risks and benefits. While PRK is safe and effective, the risk of getting corneal haze, especially in high myopia, is high. Postoperative pain, slow rehabilitation, and a long stabilization period are other limiting factors in PRK. LASIK has no postoperative pain, a faster recovery period, less regression, and no haze even in high myopia. On the other hand, it is considered to be a higher risk procedure because of flap-related complications (free cap, incomplete flap, irregular flap, button holes, and lost flaps), interface related complications (epithelial ingrowth, deep lamellar keratitis, and interface debris), flap-related corneal biomechanical instability, and iatrogenic keratectasia.1-9 LASEK and Epi-LASIK may combine the advan- Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008 216 tages of PRK and LASIK while avoiding the disadvantages of both.6,10-13 They avoid all of the flap-related complications and the risk of keratectasia associated with LASIK and have relatively faster recovery periods with slightly less pain and haze than PRK. LASEK, which involves the creation of an epithelial flap with dilute alcohol solution, is effective in treating low to moderate refractive errors. Despite the encouraging clinical results of LASEK, the toxic effect of alcohol on the epithelium and the underlying stroma remain a concern.14 Epi-LASIK represents a recent development in refractive surgery technology and makes use of a proprietary motorized blunt oscillating blade to mechanically separate the corneal epithelium en toto from the stroma, without the use of alcohol or chemicals.15,16 There is a recent trend towards surface ablation for correcting refractive errors. LASEK or Epi-LASIK are good choices for patients with low to moderate myopia and myopic astigmatism, corneal thinning with no signs of keratoconus, extreme keratometric values, i.e. steep or flat corneas, deep set eyes and small palpebral fissure, recurrent erosion syndrome, dry eye, glaucoma suspect, a wide scotopic pupil, scleral buckle, and for patients who are more predisposed to trauma like military personnel and athletes. All of these aspects should be carefully analyzed when choosing the procedure which fits the patient’s needs and expectations, with special emphasis on patient personality, occupation, corneal thickness and curvature, pupil size, corneal and ocular pathology, and degree of ametropia. Pain tolerance is a very important factor that may influence the choice of surface ablation vs. LASIK. While the corneal flap might frighten some patients, postoperative pain and discomfort may stop others from undergoing surface ablation. Another important issue is corneal thickness and biomechanical stability of the cornea after the procedure. The presence of low corneal thickness may lead to keratectasia after LASIK. It is known that once the flap is formed, it no longer significantly contributes to the biomechanical stability of the cornea. The remaining bed, hence, is the determining part of the corneal strength and should not be less than 250ºm or not less than half the original corneal thickness. Extreme keratometric values are risk factors for intraoperative flap-related complications. Steep corneas (> 48D) have a risk of buttonhole and thin flaps, while flat corneas (<40D) have risk of a free caps. This, in-turn may lead to asymmetric astigmatism and irregular ablation pattern. LASEK and EpiLASIK may be considered for these kinds of corneas to avoid such complications. Postoperative glare and halos are related in part to pupil size and optical zone treatment. The ablation zone should be larger than the pupil size in order to avoid such complications. The ablation zone is usually reduced to preserve corneal tissues in LASIK for small pupils but not for larger pupils. Patients with large pupils will benefit from LASEK or Epi-LASIK as this may allow increasing the ablation zone without endangering the remaining bed. Presence of ocular pathologies will influence the procedure choice. For example, dry eye patients are more prone to neurotrophic keratitis after LASIK than after LASEK and Epi-LASIK since the LASIK flap transects the corneal nerve. Patients with glaucoma and nerve fiber layer loss may be at risk of exacerbation of the condition due to the acute rise in intraocular pressure caused by the suction ring. Epi-LASIK is not recommended for patients who have had any previous corneal surgery or pathology that could have damaged Bowman’s layer including RK, LASIK, PRK, LASEK, Epi-LASIK, corneal ulcer, and corneal scars. In a retrospective non-comparative consecutive case series, we evaluated this technique for the correction of low to moderate myopia and myopic astigmatism. PATIENTS AND METHODS Patients This study comprised 69 eyes of 40 consecutive patients treated at the Massachusetts Eye and Ear Infirmary. The charts of these patients were retrospectively reviewed. Sixty one eyes were aimed for full correction of ametropia while 8 eyes were intentionally under-corrected. These later 8 eyes were excluded from further analysis. We also excluded all the patients with previous history of corneal or refractive surgery or corneal diseases that could affect epithelial or stromal healing. All study patients had stable refraction prior to surgery. All operations were performed by the same surgeon. This study was approved by the Institutional Review Board of the Massachusetts Eye and Ear Infirmary. The preoperative evaluation included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest and cycloplegic refractions, ocular dominance, slit lamp examination, keratometry, Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008 217 tonometry, pachymetry, computerized videokeratography (Orbscan), mesopic pupil size measurement using a pupillometer, and dilated fundus examination. Surgical Procedure The periocular skin around the operative eye was cleaned with 5% betadine solution and dried with a sterile gauze. A sterile drape was placed around the eye, and a drop of topical anesthetic (0.5% proparacaine) was instilled. A lid speculum was inserted to ensure adequate exposure. After irrigation with balanced salt solution, the corneal epithelium was dried with sponge and the cornea was marked with a standard LASIK marker, followed by irrigation to remove any ink remnants. The subepithelial separator used was the Visijet/ Gebauer EpiLift microkeratome. The preassembled handpiece was applied to the eye, with the central circular opening centration around the limbus. The suction was activated by a foot pedal. By depressing the foot pedal, the oscillating blade moved across the corneal plane, separating the epithelium, leaving a 2to 3-mm nasal hinge. The suction was released, and the device was removed from the eye. The epithelial sheet was reflected nasally using a moistened Merocel sponge or a spatula, revealing the underlying corneal stroma. The exposed area had a diameter of approximately 9 mm. Excimer laser ablation was initiated immediately thereafter. All treatments were performed with the VISX S4; (VISX Inc, Santa Clara, CA) excimer laser, and corrections attempted to achieve emmetropia. The treatment zone in each case equaled patient’s mesopic pupil measurement and ranged from 6 to 8 mm. The epithelial sheet was carefully repositioned using the straight part of an anterior chamber irrigating cannula, with intermittent irrigation with balanced salt solution to help facilitate proper repositioning of the epithelial sheet. The separated epithelial sheet often extends beyond the original position when repositioned. Care was taken to realign the epithelial flap using the previous marks and to avoid epithelial defects. A combination of 0.1% diclofenac sodium, moxifloxacin and 1% prednisolone acetate eye drops were applied to the eye. A bandage contact lens (Soflens 66, Bausch and Lomb) was placed thereafter, and kept in place until complete re-epithelization of the corneal surface. The postoperative regimen included topical moxifloxacin and 1% prednisolone acetate eyedrops 4 times per day for 1 week. The topical steroid was continued for another week and tapered over two months. Lubrication was prescribed as and when required. Patients were reviewed every day or every other day until corneal epithelial healing was complete. After complete re-epithelization, patients were followed up at 1 and 3 months. At postoperative day 1 the patients were asked by the examining physician to grade the severity of pain as follows: no pain, mild, moderate or severe pain. Subepithelial haze was graded as follows: 0 = clear cornea, +0.5 = trace haze that was barely visible on slitbeam illumination, +1 = mild haze that was easly visible on slit-beam illumination, +2=dense patches of haze affecting the vision, +3 = moderate haze somewhat obscuring iris details and 4 = marked haze obscuring iris details. RESULTS Sixty one eyes of 40 patients who underwent EpiLASIK were studied, 17 patients were male and 23 were female. The mean age was 36.8± 8.8 years (range 2254 years, median 34). The mean preoperative spherical equivalent refraction was -3.9 diopters (D) ± 1.6 D (range -.75 to -7.00 D). The mean preoperative LogMAR BSCVA was 0.0131±.041 (range -.10 to .12). The mean follow up period was 14.2 ± 8.6 weeks (range 4 to 35 weeks). Epithelial Separation and Postoperative Re-epithelization Epithelial separation was successfully performed with the epikeratome in all eyes without complications. Tow eyes had a small island of epithelium on the surface which was removed with a blade. The epithelium was easily repositioned over the corneal surface and the edges were aligned to the initial margin but often the epithelial flap extended beyond the margin. Postoperatively the epithelium remained attached without significant breakdown or dislodgement. A front of new epithelium migrated from the corneal periphery toward the center of the corneal surface. As healing progressed, the migrating new epithelium gradually replaced the epithelial sheet over 3-7 days. The mean time for complete epithelization was 6.2 ± 1.4 days (Fig. 1). Efficacy The mean LogMAR UCVA at day 1, 7, and at the final visit were -0.38±0.22 (range -1.3 to 0), -.25±.18 (range -.7 to 0), -.079±.13 (range -.48 to .12) respec- Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008 218 Figure 1. Epithelization time. Figure 2. LogMAR uncorrected visual acuity. tively (Fig.2). 75% of eyes had UCVA of 20/40 or better by postoperative day 7. At the final visit, 95% and 70.5% of eyes had UCVA of 20/40 and 20/25 or better respectively (Fig. 3). The efficacy index which is the ratio of mean postoperative UCVA to mean postoperative BSCVA was 0.81. of BSCVA. One eye underwent PTK with Mitomycin C which led to improvement of his UCVA to 20/30. The third eye had grade 1 haze which resulted in a reduction of BSCVA from 20/16 preoperatively to 20/ 25 postoperatively. Overall, the safety index which is the ratio of mean postoperative BSCVA to mean preoperative BSCVA at the final visit was 0.98 Predictability The mean postoperative spherical equivalent was -.27±0.53D (range -2.50 to 0.50D). Forty five eyes (73.8%) were within ± 0.50 D and 58 eyes (95.1%) were within ± 1.00 D of the attempted correction (Fig. 4). Safety The mean postoperative BSCVA LogMAR was 0.0039 ± 0.053 (range -0.18 to 0.1). At the final follow-up visit, 3 eyes (4.9%) lost two lines (Fig.5). One patient had grade 2 haze in both eyes and lost 2 lines Figure 3. Uncorrected visual acuity at day1, 7, and at the final visit. Corneal Haze and Postoperative Complications At the final visit, 93.4% of eyes had clear corneas or only trace haze. Only 3 eyes developed grade 1or 2 haze. No eye developed grade 3 or 4 haze. No other complications were observed (Fig. 6). Postoperative Pain 29.5% of patients experienced no pain, 59% had mild pain, and 3 patients (4.9%) had moderate pain. no patient reported severe pain (Fig. 7). Figure 4. Percentage of eyes within ± 0.50 D and ± 1.0D. Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008 219 DISCUSSION Figure 5. Difference of BSCVA (gain/loss) lines from the preoperative baseline. Figure 6. Corneal haze score. Figure 7. Pain score. A major advantage of surface ablation over LASIK is the avoidance of flap-related complications (buttonhole, free cap, incomplete microkeratome pass, epithelial ingrowth, deep lamellar keratitis, flap melt, interface debris, and traumatic flap dislocation). While iatrogenic keratectasia can occur after LASIK, it is unheard of after surface ablation. PRK, LASEK and Epi-LASIK share the biomechanical advantage of surface ablation; however, EpiLASIK was introduced with a hope to overcome the main drawbacks of both PRK and LASEK, namely pain, haze and epithelial toxicity caused by alcohol. The epikeratome separates, rather than cuts, epithelium from Bowman’s membrane with no toxicity from alcohol.17 Mechanical corneal epithelial debridement results in keratocyte cell loss through programmed cell death (apoptosis) within hours of debridement.18-20 The lost keratocytes are replaced through proliferation and migration of the peripheral keratocytes which change their phenotype to that of myofibroblast-like cells. This is accompanied with overproduction of collagen and glycosaminoglycans that may result in corneal haze. 21 It has been shown that keratocyte apoptosis may be reduced with application of amniotic membrane 22 or collagen shields. 23 Mohan et al found that keratocyte apoptosis occurs in the debrided area but not beneath some epithelial islands. 24 The corneal epithelial sheet is essential in maintaining balanced epithelial stromal interaction and, if damaged, may lead to production of inflammatory cytokines 25,26 and myofibroblast transformation.21 Preserving the epithelial flap may prevent inflammatory cytokine production from the damaged epithelial cells that occurs during epithelial debridement in PRK and render the basement membrane in place to support the epithelial sheet. The epithelial flap may also serve as a mechanical barrier between the tear film and the bare stroma. This may inhibit the corneolacrimal reflex and reduce influx of tear fluid which contains many factors such as Fas antigen and Fas ligand, 27 transforming growth factor beta, 28 and tumor necrosis factor alpha.24,29 Furthermore the viable epithelial flap may speed healing and visual recovery, reduce discomfort, and reduce the incidence of haze. In our series the mean epithelization time post operatively was 6.2 ± 1.4 days (range 3-8 days). Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008 220 98.2% of eyes (98.2%) had complete epithelization by the postoperative day 7, and only one eye had complete epithelization on postoperative day 8. This is comparable to the previous reports on Epi-LASIK16 and LASEK5,30-33 which described epithelization time ranging from 3-9 days. As in all surface ablation procedures, pain remains a limiting factor for Epi-LASIK. In our study, 94.7% of eyes had no or minimal pain. Although Epi-LASIK is associated with more pain than LASIK, results of our study as well as previous reports suggests16 that Epi-LASIK may be associated with less discomfort than LASEK. This may be attributed to better viability of epithelial cells after Epi-LASIK compared to alcohol assisted epithelial removal in LASEK. Forty six percent of eyes had UCVA of 20/40 or better at postoperative day 1. This was improved to 75% by postoperative day 7. At the final visit, 95% of eyes had UCVA 20/40 or better and 70.5% of 20/25 or better. The relatively slower visual recovery after Epi-LASIK is similar to the pattern of visual recovery after LASEK and PRK5,12,31-36 rather than after LASIK. This is apparently due to epithelial wound healing process. The main drawback of surface ablation, including Epi-LASIK is the risk of haze formation especially for higher degrees of myopia. Although the safety index in our study was near 1 at the final postoperative visit and most patients had no or trace haze (93.4%), 3 eyes lost 2 lines of BSCVA due to haze formation. One eye necessitated the use of Mitomycin C for treatment of haze. This study has certain limitations: 1. The retrospective nature of the study. 2. Relatively short duration of follow-up. 3. The lack of standardized pain scoring scale. In conclusion, although the parameters measured in this study such as haze, UCVA, BCVA, Spherical equivalent can change after 3 months, our results suggest that Epi-LASIK has a good safety, efficacy, and predictability profile. Despite it is a very promising procedure for low to moderate myopia, haze formation is still a major concern, especially in higher degrees of ametropia. Further prospective controlled studies with longer follow-up are needed to evaluate the long-term safety and stability of EpiLASIK. REFERENCES 1. Lui MM, Silas MA, Fugishima H. 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Laser epithelial keratomileusis for myopia with the autonomous laser. J Refract Surg 2002;18(3):217-224. Shah S, Sebai Sarhan AR, Doyle SJ, Pillai CT, Dua HS. The epithelial flap for photorefractive keratectomy. Br J Ophthalmol. 2001 Apr;85(4):393-396. Saudi Journal of Ophthalmology, Volume 22, No. 4, October – December 2008