Journal of Refractive Surgery

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Corneal Epithelial Damage During LASIK: A Review of 1873 Eyes

Ying-Ting Chen, MD; Sung-Huei Tseng, MD; Mi-Chia Ma, PhD; Fu-Chin Huang, MD; Yi-Yu Tsai, MD

Abstract

ABSTRACT

PURPOSE: To assess the incidence, risk factors, management, and sequelae of intraoperative epithelial damage during LASIK using a linearly advancing microkeratome.

METHODS: Chart review of 1873 eyes (956 patients) that underwent primary LASIK using the Automated Corneal Sha per microkeratome and the VISX Star S2 excimer laser. The main outcome measure was the incidence of intraoperative epithelial damage (patch of loosened epithelium with or without any frank epithelial defect). Univariate and multivariate logistic regression were performed to identify risk factors for intraoperative epithelial damage.

RESULTS: Intraoperative epithelial damage occurred in 31 (1.66%) of 1873 eyes. The incidence of intraoperative epithelial damage increased with increasing patient age (odds ratio [OR] 1.095/decade; 95% confidence interval [Cl] 1.002 to 1.197, P=.045) and increasing years of contact lens wear (OR 1.136, 95% Cl 1.024 to 1.261, P=. 016). No correlation was found for gender, corneal curvature, central corneal thickness, microkeratome plate depth, or preoperative or postoperative refraction. The risk of intraoperative epithelial damage was significantly higher in the second eye if damage occurred in the first eye (66.7% versus 0.67%, OR 298.7, Cl 78.2 to 1141.2, P<.001). Epithelial damage was managed successfully intraoperatively in all 31 eyes; recurrent corneal erosion was noted 4 months postoperatively in 1 eye but resolved after anterior stromal puncture.

CONCLUSIONS: The risk for intraoperative epithelial damage during LASIK increases with patient age, years of contact lens wear, and intraoperative epithelial damage in the first eye during simultaneous bilateral LASIK, but with proper intraoperative management, postoperative sequelae are rare. [J Refract Surg. 2007;23:916923.]

Abstract

ABSTRACT

PURPOSE: To assess the incidence, risk factors, management, and sequelae of intraoperative epithelial damage during LASIK using a linearly advancing microkeratome.

METHODS: Chart review of 1873 eyes (956 patients) that underwent primary LASIK using the Automated Corneal Sha per microkeratome and the VISX Star S2 excimer laser. The main outcome measure was the incidence of intraoperative epithelial damage (patch of loosened epithelium with or without any frank epithelial defect). Univariate and multivariate logistic regression were performed to identify risk factors for intraoperative epithelial damage.

RESULTS: Intraoperative epithelial damage occurred in 31 (1.66%) of 1873 eyes. The incidence of intraoperative epithelial damage increased with increasing patient age (odds ratio [OR] 1.095/decade; 95% confidence interval [Cl] 1.002 to 1.197, P=.045) and increasing years of contact lens wear (OR 1.136, 95% Cl 1.024 to 1.261, P=. 016). No correlation was found for gender, corneal curvature, central corneal thickness, microkeratome plate depth, or preoperative or postoperative refraction. The risk of intraoperative epithelial damage was significantly higher in the second eye if damage occurred in the first eye (66.7% versus 0.67%, OR 298.7, Cl 78.2 to 1141.2, P<.001). Epithelial damage was managed successfully intraoperatively in all 31 eyes; recurrent corneal erosion was noted 4 months postoperatively in 1 eye but resolved after anterior stromal puncture.

CONCLUSIONS: The risk for intraoperative epithelial damage during LASIK increases with patient age, years of contact lens wear, and intraoperative epithelial damage in the first eye during simultaneous bilateral LASIK, but with proper intraoperative management, postoperative sequelae are rare. [J Refract Surg. 2007;23:916923.]

During the past decade, LASIK has become the mainstay surgical procedure for the correction of refractive errors. Compared to surface ablation procedures, LASIK offers more rapid vision recovery, less postoperative pain, shortened duration of corticosteroid therapy, and minimal distortion of Bowman's layer and the epithelium.1 Although LASIK is considered to be relatively safe, it can lead to complications; the most widely reported complications include flap-related complications (incomplete or irregularly thin flap), diffuse lamellar keratitis, and epithelial ingrowth.24 There have been a number of reports in recent years on the consequences of intraoperative epithelial damage resulting from the traverse of the microkeratome,5"15 including delayed recovery of vision,16 recurrent epithelial erosion,17 diffuse lamellar keratitis,2 epithelial ingrowth,34 and microbial keratitis.18

Studies of preoperative risk factors have identified a higher incidence of intraoperative epithelial damage in patients with diabetic epitheliopathy,19 dry eye syndrome, or corneal epithelial basement membrane disease.5 Studies of intraoperative risk factors have focused on the design of the microkeratome, in particular the degree of mechanical friction associated with its use.9 Most studies have reported on the rotational Hansatome microkeratome (Bausch & Lomb, Rochester, NY),691114 possibly because of its wide popularity.

Little has been reported on how to manage intraoperative epithelial damage during LASIK to prevent postoperative sequelae. Therefore, this study was conducted to investigate the incidence and risk factors for intraoperative epithelial damage in a large series of patients undergoing LASIK with a linearly advancing microkeratome. In addition, the effectiveness of our protocol for the management of intraoperative epithelial damage in decreasing the risk of postoperative sequelae was assessed.

PATIENTS AND METHODS

STUDY POPULATION

The medical charts of 956 patients (1873 eyes) who underwent unilateral or bilateral simultaneous LASIK between August 1998 and March 2003 were reviewed. All surgeries were performed by the same surgeon (S.H.T.) using the same equipment and surgical technique. Exclusion criteria were preexisting ocular disease including recurrent corneal erosion, anterior basement membrane dystrophy, keratoconus, and severe dry eye (Schirmer's value <3 mm, apparent superficial punctuate keratopathy, or secondary Sjogren's syndrome), or systemic disease including diabetes, thyroid disease, or autoimmune disease. Patients who wore contact lenses were advised to discontinue wear at least 1 week (soft lenses) or 3 weeks (hard lenses) before surgery.

SURGICAL TECHNIQUE

Preoperative anesthesia consisted of a single drop of 0.5% proparacaine (Alcon Laboratories Ine, Ft Worth, Tex) instilled approximately 3 minutes before surgery, followed by another drop immediately before sterilization and draping of the surgical field. The Automatic Corneal Shaper (ACS; Chiron Vision, Irvine, Calif) with either a 160-?p? or a 130-?p? plate was used to create the flap; the 130-?p? plate was used for eyes with thinner corneas or higher myopia to preserve posterior corneal stromal thickness of at least 250 pm after laser ablation. Specifically, the choice of 130-?p? plate depended on the preoperative corneal thickness data and the presumed laser ablation depth.

The suction ring was applied, and a Barraquer applanation tonometer was used to verify the intraocular pressure was >65 mmHg. Immediately before the microkeratome was activated, several drops of balanced salt solution were applied to the corneal surface. The microkeratome was advanced across the cornea by gears on the tracks until it stopped to leave a nasal hinge. The entire suction time was approximately 30 seconds.

The flap then was lifted nasally and supported by a small piece of moist cellulose surgical sponge (Merocel; Medtronic, Jacksonville, FIa) to protect the epithelial layer. A 193-nm argon fluoride excimer laser (Smooth Scan; VISX Ine, Santa Clara, Calif) was used for stromal ablation; the radiant exposure was 160 mj/cm2 and the pulse reposition rate was 10 Hz. The diameter of ablation was 6 mm in all eyes. The laser was programmed with the desired manifest refraction spherical equivalent; the time of central ablation ranged between 9.8 and 78.3 seconds. After laser ablation, the corneal flap was repositioned.

Postoperatively, norfloxacin 0.3% and fluorometholone 0.1% (FML; Allergan, Irvine, Calif) were applied topically four times daily for 3 days and 1 week, respectively. Patients were examined on postoperative day 1 and again 1, 4, and 16 weeks after LASIK, with additional visits as indicated for management of sequelae of intraoperative epithelial damage or other unanticipated events.

For this study, intraoperative epithelial damage was defined as an area of epithelial loosening or loss that was clearly visible under the surgical microscope (representing an area larger than 1X1 mm2 that did not reposition spontaneously).

INTRAOPERATIVE MANAGEMENT OF EPITHELIAL DAMAGE

The first step in managing intraoperative epithelial damage was to inspect the corneal flap to determine the extent of damage. When only the epithelial layer was involved, LASIK proceeded as planned with corneal flap lifting, laser ablation, and flap repositioning, followed by vigorous stroking of the repositioned corneal flap from nasal to temporal with a moist cellulose surgical sponge to ensure the flap was tightly and smoothly positioned over the stromal bed. Compared to cases of uneventful LASIK, in cases of intraoperative epithelial damage, we waited for a longer period (approximately 5 minutes) for the flap to attach more firmly, particularly the edge adjacent to the intraoperative epithelial damage. Meanwhile, the intraoperative epithelial damage was managed in one of two ways depending on the nature of the damage.

For cases in which the loosened or sloughing portion of corneal epithelium was still attached and appeared to be intact, a dry cellulose sponge was used to return the separated portion of corneal epithelium as precisely as possible to its original position. Gentle manipulation was crucial to avoid inadvertently disrupting attachment of the underlying flap layers. Such manipulations sometimes required several minutes to reposition the epithelium satisfactorily; during repositioning, one or two drops of balanced salt solution were applied to the rest of the corneal surface to prevent drying. For cases in which the epithelial damage involved tearing or severe damage to the epithelium such that there was a frank defect, the necrotic epithelium was excised with Vanas scissors (Katena Products Ine, Denville, NJ) or fine jeweler's forceps, leaving a margin of healthy tissue.

Table

TABLE 1Characteristics of 956 Patients (1873 Eyes) Who Underwent Primary LASIK

TABLE 1

Characteristics of 956 Patients (1873 Eyes) Who Underwent Primary LASIK

At the conclusion of the procedure, a soft bandage contact lens was applied to promote reattachment of the sloughed corneal epithelium or re-epithelialization of an epithelial defect. Patients were instructed to instill artificial tears every 2 hours to keep the corneal surface lubricated. A few days postoperatively, the bandage contact lens was removed when slit-lamp microscopy revealed no apparent epithelial abnormalities.

STATISTICAL ANALYSIS

The following variables were recorded for each eye: patient age and gender, history (years) of contact lens use, pre- and postoperative manifest refraction spherical equivalent, preoperative central corneal thickness as measured by ultrasound pachymetry (Cornea Gauge Plus; Sonogage Ine, Cleveland, Ohio), average corneal curvature determined by simulated keratometry from computerized corneal topography (Computed Anatomy, New York, NY), and the depth of the microkeratome plate used for LASIK in that eye (160 or 130 pm).

Statistical Package for Social Sciences version 10.0 for Windows (SPSS Ine, Chicago, 111) was used for data analysis. Univariate and multivariate models were used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of intraoperative epithelial damage associated with individual variables or combinations of variables. Differences in group means for eyes with and without intraoperative epithelial damage were tested for statistical significance at a level ofP<.05.

Figure 1. Sloughing of the corneal epithelium caused by microkeratome abrasion during LASIK manifests as a balloon shape adjacent to the inferior margin of the corneal flap.

Figure 1. Sloughing of the corneal epithelium caused by microkeratome abrasion during LASIK manifests as a balloon shape adjacent to the inferior margin of the corneal flap.

RESULTS

Of the total of 956 patients (1873 eyes) in this series, 671 were women and 285 were men. Nine hundred seventeen patients underwent bilateral LASIK surgery. Patient characteristics are listed in Table 1. In most cases (1839 [98.2%] of eyes), the 160-pm plate was used for LASIK; in 34 (1.8%) eyes, the 130-pm plate was used to create a thinner corneal flap so as to preserve a posterior stromal thickness ^250 pm.

Intraoperative epithelial damage occurred in 31 (1.66%) eyes of 21 (2.20%) patients. In the majority of cases (25 [81.6%] eyes), damage consisted of corneal epithelium sloughing (Fig 1). In the remaining cases (6 [19.4%] eyes), tearing of the epithelial sheet led to a frank defect, which tended to occur near the superior or inferior margin of the corneal flap and rarely extended to the central cornea.

Postoperative complications of intraoperative epithelial damage were rare. During follow-up ranging from 6 months to 3 years, the only complication was recurrent corneal erosion in one patient (one eye). This was treated successfully with anterior stromal puncture.

Older patient age (P=. 02 3) and more years of contact lens wear (P=. 01 7) were the only two factors that significantly increased the risk for intraoperative epithelial damage (Table 2). Multivariate regression analysis showed an increase in OR of 1.095 for intraoperative epithelial damage (95% CI 1.002 to 1.197, P=.045) for every decade of increase in patient age (Fig 2) and an increase in OR of 1.136 (95% CI 1.024 to 1.261, P=.016) for every additional 5 years of contact lens wear (Fig 3).

Among the 917 patients who underwent simultaneous bilateral LASIK, 15 (1.64%) patients had intraoperative epithelial damage in both the first and second eyes (Table 3), leading to a conditional 66.7% probability of intraoperative epithelial damage in the second eye for patients undergoing simultaneous bilateral procedures. The OR for intraoperative epithelial damage in the second eye was 298.7 (95% CI 78.2 to 1141.2, P<.001).

Figure 2. The incidence (predictability) of corneal epithelial damage during LASIK increases as a function of age in 956 patients who underwent primary LASIK with the Automatic Corneal Shaper microkeratome.Figure 3. The incidence (predictability) of corneal epithelial damage during LASIK increases as a function of years of contact lens wear in 956 patients who underwent primary LASIK with the Automatic Corneal Shaper microkeratome. CL Hx = contact lens history

Figure 2. The incidence (predictability) of corneal epithelial damage during LASIK increases as a function of age in 956 patients who underwent primary LASIK with the Automatic Corneal Shaper microkeratome.

Figure 3. The incidence (predictability) of corneal epithelial damage during LASIK increases as a function of years of contact lens wear in 956 patients who underwent primary LASIK with the Automatic Corneal Shaper microkeratome. CL Hx = contact lens history

DISCUSSION

Damage to the corneal epithelium during LASIK may delay recovery in vision, cause postoperative discomfort, and lead to wound-healing complications. In this series of 956 patients (1873 eyes) who underwent primary LASIK, intraoperative epithelial damage occurred in 31 (1.66%) eyes. This compares well with incidences of intraoperative epithelial damage ranging between 0.049% and 22.6% for other case series reported in the literature (Table 4).615 In our series, more than 80% of intraoperative epithelial damage manifested as corneal epithelium sloughing, that is, detachment of an intact epithelial sheet from the underlying stroma. With meticulous intraoperative management, even the more serious cases of epithelial damage in our series healed, and during postoperative follow-up ^6 months, only one complication occurred in 1 (0.05%) eye.

RISK FACTORS FOR INTRAOPERATIVE EPITHELIAL DAMAGE

Microkeratome Design. As shown in Table 4, the incidence of intraoperative epithelial damage varied widely for different microkeratomes used for LASIK. However, caution is necessary when interpreting the incidence of intraoperative epithelial damage among these studies because not only the microkeratome per se but also patient demographics, eye drop regimen, and surgical procedure significantly influence the results. In a study comparing the incidence of intraoperative epithelial damage with microkeratomes of different cutting design,9 a higher incidence of intraoperative epithelial damage occurred with the use of the standard Hansatome microkeratome, which has a rotational cutting design, compared to the Amadeus (Advanced Medical Optics, Santa Ana, Calif), which has a linearly advancing cutting design.9 With improvements in the microkeratome head, the zero-compression Hansatome recently has been shown to significantly reduce the incidence of intraoperative epithelial damage.1214

In our series, we used a linearly advancing ACS microkeratome, and our incidence of intraoperative epithelial damage in 37 of 1873 eyes (1.66%) was compatible with those reported for the linearly advancing microkeratomes used in other studies.9,15 However, because of its complex assembly and higher incidence of flaprelated complications, the ACS is no longer widely used, and we found no other recent reports on the incidence of intraoperative epithelial damage for the ACS microkeratome. Based on our results and those reported by Jabbur and O'Brien9 and Carrillo et al,15 microkeratomes with a linearly advancing design seem to minimize the risk of intraoperative epithelial damage; however, further comparative studies of linearly advancing and rotational microkeratomes may be warranted.

As for the use of the femtosecond laser to create the corneal flap, the friction-free process takes place through a glass applanation plate that is fixed to the eye with a low-pressure suction ring. With proper maneuvering, the probability of epithelial injury is likely to be zero. Kezirian and Stonecipher13 compared epithelial integrity using the IntraLase (Irvine, Calif) femtosecond laser and the Hansatome and CarriazoBarraquer (Moria, Antony, France) microkeratomes. The incidence of epithelial injury was 7.7% for the Hansatome microkeratome and 9.6% for the CarriazoBarraquer microkeratomes compared with no epithelial injuries for the femtosecond laser.

Table

TABLE 2Results of Logistic Regression Analyses of Risk Factors for Intraoperative Epithelial Damage in 956 Patients (1873 Eyes) Who Underwent Bilateral LASIK

TABLE 2

Results of Logistic Regression Analyses of Risk Factors for Intraoperative Epithelial Damage in 956 Patients (1873 Eyes) Who Underwent Bilateral LASIK

Table

TABLE 3Risk for Intraoperative Epithelial Damage in the Second Eye During Simultaneous Bilateral LASIK in 917 Patients (1834 Eyes)

TABLE 3

Risk for Intraoperative Epithelial Damage in the Second Eye During Simultaneous Bilateral LASIK in 917 Patients (1834 Eyes)

Increasing Patient Age. As shown in Table 4, other studies also have found increasing patient age to be a significant risk factor for intraoperative epithelial damage.79,14 The effect of age on risk for intraoperative epithelial damage may be associated with age-related changes in the structure of the corneal epithelium adhesion complex. This complex is composed of intermediate filaments, hemidesmosomes, basement membrane, and anchoring fibrils.20

As we reported recently, the cleavage plane of traumatic recurrent corneal erosion is at the level of the anchoring fibrils.21 Because the mechanism for intraoperative epithelial damage during LASIK is similar to the mechanism for traumatic recurrent corneal erosion, we believe the pathophysiology of intraoperative epithelial damage during LASIK is probably similar as well and most likely involves disruption, by friction from the microkeratome plate, of the structure of the anchoring fibrils in the adhesion complex. These anchoring fibrils become more susceptible to disruption during the natural aging process as the membrane reduplication increases in thickness beyond the length of the fibrils. This weakens the attachment of the anchoring fibrils to Bowman's layer and thus compromises the adhesion of the corneal epithelium.22 Moreover, exposure to ultraviolet energy in sunlight may damage the desmosomes and hemidesmosomal connections between the epithelium and its basement membrane, also weakening the adhesion of the epithelium.23

Another characteristic of aging is a decrease in tear quantity and quality.24 Insufficient tear film may increase the risk for intraoperative epithelial damage due to friction between the microkeratome plate and the cornea. For these reasons, older patients should be informed of their higher risk for intraoperative epithelial damage, and the increasing risk with increasing age should be included on the form used to obtain written consent for LASIK. In the current study, the relatively low incidence of intraoperative epithelial damage may be attributed partly to the younger patients and also to the strict exclusion of severe dry eye.

Table

TABLE 4Literature Reports of Intraoperative Epithelial Damage During LASIK

TABLE 4

Literature Reports of Intraoperative Epithelial Damage During LASIK

Prolonged History of Contact Lens Wear. Another significant risk factor for intraoperative epithelial damage that was identified in our study is a longer history of contact lens wear. This factor has not been reported previously in the literature. Except for the associated dry eye status, it is well known that long-term contact lens wear may cause a number of pathophysiological changes in the corneal epithelium, including a decreased number of epithelial layers, a reduction in hemidesmosome density, and undulations in the basement membrane.25 Even when the anchoring fibrils remain normal, a decrease in the number of hemidesmosomes might cause intraoperative epithelial damage.

Intraoperative Epithelial Damage in the First Eye. In our study as well as in a previously reported study,7 there was a high degree of correlation between the occurrence of intraoperative epithelial damage during LASIK in the first eye and intraoperative epithelial damage during LASIK in the second eye for patients undergoing bilateral LASIK. In our study, for patients undergoing bilateral LASIK in whom intraoperative epithelial damage occurred in the first eye, the chance of intraoperative epithelial damage occurring in the second eye was 66.7%. This concurrence is reasonable considering the other risk factors that were identified for intraoperative epithelial damage (ie, older age and longer history of contact lens wear) affect both eyes.

In cases in which intraoperative epithelial damage occurs in the first eye, it generally is recommended to defer LASIK in the contralateral eye or to use a surface ablation procedure such as photorefractive keratectomy. However, the results in our series show that when epithelial damage is successfully managed intraoperatively, it is not a contraindication to performing LASIK in the second eye during the same operation. In fact, intraoperative epithelial damage in the first eye prepared us for the likelihood of intraoperative epithelial damage in the second eye, and being aware of the increased risk in the second eye may have played a role in the generally less severe epithelial damage we usually saw in the second eye. In our series, the only postoperative complication developed in the first operated eye of a patient with bilateral intraoperative epithelial damage. Nevertheless, in cases in which intraoperative epithelial damage occurs in the first eye, we recommend surgeons discuss the situation with patients and decide jointly whether to proceed with LASIK or surface ablation in the second eye or to defer surgery on the second eye until after the first eye heals.

MINIMIZING RISK OF INTRAOPERATIVE EPITHELIAL DAMAGE

The femtosecond laser is effective in preventing intraoperative epithelial damage during creation of the corneal flap.13 However, to minimize the risk of intraoperative epithelial damage associated with use of a mechanical microkeratome, several strategies are recommended. These include avoiding LASIK in patients known to have epithelial basement membrane dystrophy or an ocular surface disorder, avoiding excessive intraoperative use of topical anesthetic agents and marking dyes, lubricating the corneal surface before use of the microkeratome, and releasing the suction ring vacuum as the microkeratome is withdrawn.7 Unfortunately, even a meticulous slit-lamp examination may fail to identify an estimated 5% of epithelial basement membrane degeneration cases in the general population.26 When looseness of the corneal epithelium is suspected, a provocative test using a microsponge applicator has been recommended.1027

MANAGEMENT OF INTRAOPERATIVE EPITHELIAL DAMAGE

Our review of the literature yielded only one report that described the management of LASIK-associated intraoperative epithelial damage, and the report focused on the principles of postoperative management.6 We believe meticulous intraoperative management of epithelial damage is critical to prevent postoperative sequelae. First, the corneal flap should be inspected closely. In our experience, except for the epithelial damage of the flap, the underlying stromal bed is adequate to proceed to laser ablation. Second, after ablation and return of the flap to its original position, secure repositioning of the flap over the underlying bed should be assured before the injured epithelial sheet is manipulated. Attention should be given particularly to the flap edge adjacent to the sloughing epithelium because edema that develops at the flap margin may encourage epithelial ingrowth.3,4 Third, a loosened epithelial sheet should be returned to its original position using dry surgical sponges, and torn portions or any rough edges of epithelium should be debrided with forceps or trimmed with Vanas scissors. Although this step is time consuming, it is essential to promote rapid reepithelialization, to prevent recurrent corneal erosion, and ultimately to optimize the quality of vision. Fourth, a bandage soft contact lens must be applied to stabilize the epithelial sheet. Patients should wear the bandage contact lens for several days or longer in cases of severe intraoperative epithelial damage. Finally, postoperative surveillance is important for early diagnosis and management of epithelial ingrowth or late recurrent corneal erosion.

Every LASIK candidate should undergo careful preoperative screening for risk factors of intraoperative epithelial damage. In this study, the risk for intraoperative epithelial damage during LASIK increased with patient age, years of contact lens wear, and intraoperative epithelial damage in the first eye during simultaneous bilateral LASIK. When intraoperative epithelial damage does occur, it should be managed immediately and meticulously to minimize the risk of postoperative complications.

REFERENCES

1. Farah SG, Azar DT, Gurdal C, Wong J. Laser in situ keratomileusis: literature review of a developing technique. J Cataract Refract Surg. 1998;24:989-1006.

2. Asano-Kato N, Toda I, Tsubota K. Severe late-onset recurrent epithelial erosion with diffuse lamellar keratitis after laser in situ keratomileusis. / Cataract Refract Surg. 2 003 ;2 9: 20192021.

3. Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol. 2000;129:746-751.

4. Asano-Kato N, Toda I, Hori-Komai Y, Takano Y, Tsubota K. Epithelial ingrowth after laser in situ keratomileusis: clinical features and possible mechanisms. Am J Ophthalmol. 2002;134:801-807.

5. Dastgheib KA, Clinch TE, Manche EE, Hersh P, Ramsey J. Sloughing of corneal epithelium and wound healing complications associated with laser in situ keratomileusis in patients with epithelial basement membrane dystrophy. Am J Ophthalmol. 2000;130:297-303.

6. Smirennaia E, Sheludchenko V, Kourenkova N, Kashnikova O. Management of corneal epithelial defects following laser in situ keratomileusis. J Refract Surg. 2 001; 17: S 196 -S 199.

7. Tekwani NH, Huang D. Risk factors for intraoperative epithelial defect in laser in situ keratomileusis. Am J Ophthalmol. 2002;134:311-316.

8. Bashour M. Risk factors for epithelial erosions in laser in situ keratomileusis. / Cataract Refract Surg. 2002;28:1780-1788.

9. Jabbur NS, O'Brien TP. Incidence of intraoperative corneal abrasions and correlation with age using the Hansatome and Amadeus microkeratomes during laser in situ keratomileusis. J Cataract Refract Surg. 2003;29:1174-1178.

10. Kenyon KR, Paz H, Greiner JV, Gip s on IK. Corneal epithelial adhesion abnormalities associated with LASIK. Ophthalmology. 2004;111:11-17.

11. Mirshahi A, Buhren J, Kohnen T. Clinical course of severe central epithelial defects in laser in situ keratomileusis. J Cataract Refract Surg. 2004;30:1636-1641.

12. Kohnen T, Terzi E, Mirshahi A, Buhren J. Intraindividual comparison of epithelial defects during laser in situ keratomileusis using standard and zero-compression Hansatome microkeratome heads . / Cataract Refract Surg. 2 0 04 ; 3 0 : 1 2 3 - 1 2 6 .

13. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. / Cataract Refract Surg. 2004;30:804-811.

14. Polk EE, Wexler SA, Kymes S. Incidence of corneal epithelial defects with the standard and zero-compression Hansatome microkeratomes. J Refract Surg. 2005;21:359-364.

15. Carrillo C, Chayet AS, Dougherty PJ, Montes M, Magallanes R, Najman J, Fleitman J, Morales A. Incidence of complications during flap creation in LASIK using the NIDEK MK-2000 microkeratomes in 26,600 cases. / Refract Surg. 2005;21:S655-S657.

16. Esquenazi S, Bui V. Long-term refractive results of myopic LASIK complicated with intraoperative epithelial defect. J Refract Surg. 2006;22:54-60.

17. Ti SE, Tan DT. Recurrent corneal erosion after laser in situ keratomileusis. Cornea. 2001;20:156-158.

18. Alio JL, Perez-Santonja JJ, Tervo T, Tabbara KF, Vesaluoma M, Smith RJ, Maddox B, Maloney RK. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. J Refract Surg. 2000;16:523-538.

19. Fraunfelder FW, Rich LF. Laser-assisted in situ keratomileusis complications in diabetes mellitus. Cornea. 2002;21:246-248.

20. Espana EM, Grueterich M, Mateo A, Romano AC, Yee SB, Yee RW, Tseng SCG. Cleavage of corneal basement membrane components by ethanol exposure in laser-assisted subepithelial keratectomy . J Cataract Refract Surg. 2 0 03 ; 2 9 : 1 1 92 - 1 1 9 7 .

21. Chen YT, Huang CW, Huang FC, Tseng SY, Tseng SH. The cleavage plane of corneal epithelial adhesion complex in traumatic recurrent corneal erosion. MoI Vis. 2006;12:196-204.

22. Alvarado J, Murphy C, Juster R. Age-related changes in the basement membrane of the human corneal epithelium. Invest Ophthalmol Vis Sci. 1983;24:1015-1028.

23. Chouinard N, Therrien JP, Mitchell DL, Robert M, Drouin R, Rouabhia M. Repeated exposures of human skin equivalent to low doses of ultraviolet-B radiation lead to changes in cellular functions and accumulation of cyclobutane pyrimidine dimers. Biochem Cell Biol. 2001;79:507-515.

24. Faragher RG, Mulholland B, Tuft SJ, Sandeman S, Khaw PT. Aging and the cornea. Br J Ophthalmol. 1997;81:814-817.

25. Madigan MC, Holden BA. Reduced epithelial adhesion after extended contact lens wear correlates with reduced hemidesmosome density in cat cornea. Invest Ophthalmol Vis Sci. 1992;33:314-323.

26. Laibson PR. Microcystic corneal dystrophy. Trans Am Ophthalmol Soc. 1976;74:488-53 1.

27. Albietz JM, Lent on LM. Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis. J Refract Surg. 2004;20:62-71.

TABLE 1

Characteristics of 956 Patients (1873 Eyes) Who Underwent Primary LASIK

TABLE 2

Results of Logistic Regression Analyses of Risk Factors for Intraoperative Epithelial Damage in 956 Patients (1873 Eyes) Who Underwent Bilateral LASIK

TABLE 3

Risk for Intraoperative Epithelial Damage in the Second Eye During Simultaneous Bilateral LASIK in 917 Patients (1834 Eyes)

TABLE 4

Literature Reports of Intraoperative Epithelial Damage During LASIK

10.3928/1081-597X-20071101-09

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