Journal of Refractive Surgery

Original Article Supplemental Data

Comparison of Single-Step Transepithelial Photorefractive Keratectomy With or Without Mitomycin C in Mild to Moderate Myopia

Soheil Adib-Moghaddam, MD; Saeed Soleyman-Jahi, MD, MPH; Ghazale Tefagh, MD; Salar Tofighi, MD; Michael A. Grentzelos, MD; George D. Kymionis, MD, PhD

Abstract

PURPOSE:

To compare efficacy and safety of single-step transepithelial photorefractive keratectomy (PRK) with or without mitomycin C (MMC) in patients with mild to moderate myopia.

METHODS:

Patients with mild to moderate myopia (≤ −5.50 diopters [D]) underwent single-step transepithelial PRK using the Amaris laser (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). Total ablation depth (epithelium and stroma) was 160 μm or less. The right eye of each patient was treated with 0.02% MMC for 10 seconds, whereas the left eye did not receive any MMC. Corneal haze, endothelial cell indices, refraction, visual acuity, contrast sensitivity, and higher order aberrations were assessed preoperatively and postoperatively.

RESULTS:

In this comparative case series, 71 patients (16 men and 55 women; 142 eyes) were enrolled. Mean patient age was 27.97 ± 5.74 years. Mean preoperative spherical equivalent of patients' right and left eyes were −3.20 ± 1.20 and −3.30 ± 1.20 diopters, respectively (P = .70); other preoperative visual parameters were also comparable. Incidence of 2+ grade of haze was detected in 1 (2.5%) right and 2 (5.0%) left eyes (P > .99) 3 to 6 months postoperatively. Incidence of 1+ degree of haze was also comparable. No eye developed 3+ degrees or more of haze. One year postoperatively, both eyes achieved comparable refraction, visual acuity, contrast sensitivity, and higher order aberrations, and no greater than trace haze was detected. MMC-treated eyes suffered a greater loss of endothelial cell density (P < .001) and showed higher variance in cell size (P = .001).

CONCLUSIONS:

Single-step transepithelial PRK with or without MMC showed similar efficacy and incidence of haze in eyes with mild to moderate myopia with total ablation depths of 160 μm or less. However, MMC-treated eyes showed a worse profile of endothelial cell indices. Applications of MMC in this subgroup of patients may be reconsidered.

[J Refract Surg. 2018;34(6):400–407.]

Abstract

PURPOSE:

To compare efficacy and safety of single-step transepithelial photorefractive keratectomy (PRK) with or without mitomycin C (MMC) in patients with mild to moderate myopia.

METHODS:

Patients with mild to moderate myopia (≤ −5.50 diopters [D]) underwent single-step transepithelial PRK using the Amaris laser (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). Total ablation depth (epithelium and stroma) was 160 μm or less. The right eye of each patient was treated with 0.02% MMC for 10 seconds, whereas the left eye did not receive any MMC. Corneal haze, endothelial cell indices, refraction, visual acuity, contrast sensitivity, and higher order aberrations were assessed preoperatively and postoperatively.

RESULTS:

In this comparative case series, 71 patients (16 men and 55 women; 142 eyes) were enrolled. Mean patient age was 27.97 ± 5.74 years. Mean preoperative spherical equivalent of patients' right and left eyes were −3.20 ± 1.20 and −3.30 ± 1.20 diopters, respectively (P = .70); other preoperative visual parameters were also comparable. Incidence of 2+ grade of haze was detected in 1 (2.5%) right and 2 (5.0%) left eyes (P > .99) 3 to 6 months postoperatively. Incidence of 1+ degree of haze was also comparable. No eye developed 3+ degrees or more of haze. One year postoperatively, both eyes achieved comparable refraction, visual acuity, contrast sensitivity, and higher order aberrations, and no greater than trace haze was detected. MMC-treated eyes suffered a greater loss of endothelial cell density (P < .001) and showed higher variance in cell size (P = .001).

CONCLUSIONS:

Single-step transepithelial PRK with or without MMC showed similar efficacy and incidence of haze in eyes with mild to moderate myopia with total ablation depths of 160 μm or less. However, MMC-treated eyes showed a worse profile of endothelial cell indices. Applications of MMC in this subgroup of patients may be reconsidered.

[J Refract Surg. 2018;34(6):400–407.]

Corneal haze is a common complication of photorefractive keratectomy (PRK). Clinically insignificant haze affects almost every eye undergoing PRK, whereas clinically significant haze affects 0.3% to 3% of the treated eyes.1 Corneal haze can reduce the efficacy of the surgery by leading to fluctuations in vision, irregular astigmatism, and myopic regression.2 Mitomycin C (MMC) has been successful in preventing haze after PRK in studies of low, medium, and high myopia.3–5 There are several studies suggesting MMC application during PRK.5–8 However, in a study of eyes with mild to moderate myopia, MMC application decreased endothelial cell density by 6 months postoperatively.9 Another study on PRK reported MMC induced endothelial cell loss by 3 months postoperatively.10

Thereafter, studies have investigated the efficacy and safety of different MMC regimens on eyes with different visual parameters to find appropriate indications of MMC application in refractive surgery. Authors reported that ablations with lower depths were less likely to induce postoperative haze.11 It was suggested that the ablation depth could be used to determine when lower doses and shorter durations of MMC application could suffice to prevent the postoperative haze in PRK and LASEK.3,12,13 Likewise, shorter durations of MMC could prevent haze formation in myopic eyes undergoing PRK with ablation depths below 65 μm without side effects up to 6 months postoperatively.3 Some researchers recommended using MMC in PRK for eyes with myopia of greater than −4.00 or −6.00 diopters and astigmatism,14 whereas others debated whether to use no MMC or reduce the dosage or application time in eyes with mild to moderate myopia.15

Transepithelial PRK was introduced in an attempt to reduce the adverse consequences of mechanical PRK; it exploits the excimer laser for ablation of both epithelium and stroma.16 In the single-step profile, transepithelial PRK ablates stroma and epithelium in a single continuous session. It has been shown to be a safe and effective alternative for alcohol-assisted and conventional PRK in myopia.16–18 In previous studies, less haze induction and more rapid healing were in favor of transepithelial PRK over conventional PRK.16,18 We previously reported promising long-term results of single-step transepithelial PRK in correction of myopia19 and hyperopia.20 The incidence of 1+ haze at 18 months after the operation was 0.68% in our myopic eyes. Incidence of 1+ haze in mild to moderate myopia was 10% and 26% at 3 months after single-step transepithelial PRK and conventional PRK, respectively.16

Therefore, there may be different indications for MMC application in transepithelial PRK. In this study, we aimed to compare efficacy, stability, and safety of single-step transepithelial PRK with or without MMC in eyes with mild to moderate myopia with an ablation depth up to 160 μm.

Patients and Methods

In this comparative case series, patients were enrolled from Bina Eye Hospital of Tehran. The protocol of the study conformed to the tenets of the Declaration of Helsinki and was approved by the institutional review board. Written informed consent was obtained from all of the cases enrolled.

Inclusion criteria were myopia of −5.50 diopters (D) or less with or without astigmatism (spherical equivalent ≤ −6.00 D) in both eyes. Patients with concurrent systemic disease with ocular involvement, ocular or corneal disease, severe dry eye, unstable refractive error during the past 12 months, previous ocular or corneal surgery, keratoconus, and night vision disturbance (eg, retinitis pigmentosa or chorioretinal atrophic changes) were excluded from the study. Hard and soft contact lenses were discontinued 4 weeks prior to the procedure.

Before and after the operation, we assessed corrected distance visual acuity, uncorrected distance visual acuity, refraction, corneal haze using slit lamp, photopic and mesopic contrast sensitivity (M&S Smart System 20/20; M&S Technologies, Inc., Niles, IL), Orbscan (Bausch & Lomb, Rochester, NY), keratometry and topography with Scout (Optikon 2000 SPA, Rome, Italy), spherical, cylindrical, coma, and trefoil higher order aberrations (HOAs), and specular microscopy (Topcon SP-3000P; Topcon Corporation, Tokyo, Japan).

Specular microscopy is a non-invasive technique to assess the structure and function of corneal endothelium by exploiting a specular reflex light with a slit lamp.21 It provides a high-magnification view of the specular light reflected from the corneal endothelium. A computer interface is used to capture the images and analysis of endothelial cell morphology. They provide endothelial cell density and morphology analysis. Endothelial cell loss is measured based on an increase in the endothelial individual cell surface (μm2), a decrease of the cell density (cell count/mm2), an increase of the polymegethism (coefficient variance of cell area), and/or pleomorphism (decreased % of hexagonal cells). Hexagonal cells are an indication of normal cells with even distribution of membrane surface tension. Normal values for specular microscopy indices for a middle-aged white adult population are as follows: cell density = 2,700 to 2,900 cells/mm2; coefficient variance of cell area = 0.22 to 0.31; and percent of hexagonal cells = 60% or greater. To measure endothelial cell indices reliably, we selected images with at least 75 cells.22

At the beginning of the ablation procedures, anesthetic drops were applied and eyes were scrubbed by povidone-iodine 10%. Each eye was irrigated with 60 cc of chilled balanced salt solution (BSS). All of the ablation procedures were done by the Amaris 500-Hz excimer laser (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany) with its integrated CAM software. The software exploits its built-in nomogram to calculate target refraction and other surgical indices based on the patient's optical data. In this study, we used the refined method of single-step transepithelial PRK to apply some modifications in determining target refraction, optical zone, and centration approach, as have been previously reported.19,20,23 Age, keratometry, central corneal thickness, and radius of corneal curvature were the main parameters considered for further individualization of the profile. In an aspheric and aberration-free ablation profile, the excimer laser was administered in a single continuous session, unlike the two distinct steps used in the older two-step transepithelial PRK, to ablate both the epithelium and stroma. During this session, the refractive ablation component of the stroma was performed prior to the epithelial ablation component. This reverse sequence of ablation maximizes the smoothing effect of the epithelium. An optical zone range of 6.1 to 7.8 mm was used. Static and dynamic cyclotorsional corrections were applied during the ablation. All procedures were performed by the same surgeon (SA-M).

The laser platform exploits a custom population-based epithelial thickness model. This model considers higher thickness in the peripheral epithelium.24 The ablation profile based on this model targets 55 μm centrally and 65 μm peripherally in an 8-mm ablation zone over the cornea. Further considerations are applied for the differential ablation rate in the epithelium compared to the stroma. These adjustments provide even laser energy delivery to different parts of the corneal surface.

We used MMC application for only the right eye of each patient. After the procedure, we applied a soaked and squeezed sponge with MMC 0.02% on the stromal bed of right eyes for 10 seconds followed by irrigation with copious chilled BSS. The left eyes were just irrigated with chilled BBS. A soft bandage high oxygen permeability contact lens (Bausch & Lomb) was placed over the cornea until full reepithelialization.

Postoperative medications were prescribed based on a modified protocol.19,20,23 Ciprofloxacin 0.5% (Ciplex; Leeford Healthcare Ltd., Ludhiana, India) eye drops every 4 hours up to 3 days, oral ibuprofen capsule 400 mg twice a day, and alprazolam tablet 1 mg daily were prescribed. If there was no corneal epithelial defect after bandage lens removal, patients were prescribed loteprednol 0.5% eye drops (Lotemax; Bausch & Lomb) every 6 hours for 2 weeks, then tapered every 2 weeks to once daily and continued up to 6 months; ciprofloxacin 0.5% eye drops every 8 hours for a week; and preservative-free artificial tears (Artelac Advanced; Bausch & Lomb) for 6 months. All patients were instructed to wear standard sunglasses to protect them from ultraviolet light.

Follow-up data at 1, 3, 6, and 12 months after the procedure were collected. Haze assessments in all follow-up visits were performed by the same clinical observer, who was blind to the study protocol. Similarly, other parameters were assessed by other investigators who were blind to the study protocol. Corneal haze grading was based on the Fantes scaling system ranging from grade 0 to 4 based on visualization of the iris and the lens.25

Statistical Analysis

We used means and standard deviations to describe continuous parameters. Both preoperative and postoperative parameters were compared between right and left eyes using the paired t test. In addition, the chi-square test was used to compare rates of haze induction between the two groups at corresponding follow-up time points. Spherical equivalent was calculated as: spherical refraction + (0.5 × cylindrical refraction). Mean spherical equivalents of successive follow-up visits were compared by repeated measure analysis of variance to evaluate stability of refraction. We referred to two-tailed P values in the analyses and a P value of .05 was considered statistically significant.

Results

In this comparative cases series, 71 patients (16 males/55 females; 142 eyes) were enrolled. Patients had documented data for 12 months of follow-up. Mean patient age was 27.97 ± 5.74 years (range: 22 to 45 years). Ranges of myopia and astigmatism were −1.00 to −5.50 and −0.25 to −2.50 D, respectively. Right and left eyes had comparable preoperative surgical and ophthalmological parameters (Table A, available in the online version of this article).

Preoperative Ophthalmologic Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRKa

Table A:

Preoperative Ophthalmologic Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRK

Both right and left eyes achieved a stable refraction by the third month of follow-up, based on insignificant (P = .32 for right eyes and P = .41 for left eyes) differences among mean refractions at 3, 6, and 12 months postoperatively (Figures 12). One year postoperatively, both eyes had comparable quantitative and qualitative visual outcomes (Figures 12, Table B, available in the online version of this article). Although baseline preoperative endothelial cell parameters were comparable between right and left eyes (Table A), we detected significant differences 1 year postoperatively (Table B); cell density loss was significantly higher in the MMC-treated right eye of the patients compared to their left eyes with no MMC application (5.1% ± 4.3% vs 2.3% ± 2.2%, P < .001). Similarly, coefficient variance of cell area was significantly higher in right eyes (33.12 ± 4.72 vs 30.23 ± 5.16, P = .001). However, differences in percentage of hexagonality were not significant between right and left eyes (56.43 ± 10.81 vs 58.77 ± 9.61, P = .15).

Standard graphs for refractive visual outcomes of eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy with mitomycin C. The figure demonstrates results of (A) postoperative uncorrected distance visual acuity (UDVA) vs preoperative corrected distance visual acuity (CDVA), (B) change of CDVA in terms of numbers of decimal lines, (C) spherical equivalent correction attempted vs achieved, (D) accuracy of spherical equivalent correction, (E) accuracy of refractive astigmatism correction, and (F) stability of postoperative spherical equivalent refraction. D = diopters

Figure 1.

Standard graphs for refractive visual outcomes of eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy with mitomycin C. The figure demonstrates results of (A) postoperative uncorrected distance visual acuity (UDVA) vs preoperative corrected distance visual acuity (CDVA), (B) change of CDVA in terms of numbers of decimal lines, (C) spherical equivalent correction attempted vs achieved, (D) accuracy of spherical equivalent correction, (E) accuracy of refractive astigmatism correction, and (F) stability of postoperative spherical equivalent refraction. D = diopters

Standard graphs for refractive visual outcomes of eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy without mitomycin C. The figure demonstrates results of (A) postoperative uncorrected distance visual acuity (UDVA) vs preoperative corrected distance visual acuity (CDVA), (B) change of CDVA in terms of numbers of decimal lines, (C) spherical equivalent correction attempted vs achieved, (D) accuracy of spherical equivalent correction, (E) accuracy of refractive astigmatism correction, and (F) stability of postoperative spherical equivalent refraction. D = diopters

Figure 2.

Standard graphs for refractive visual outcomes of eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy without mitomycin C. The figure demonstrates results of (A) postoperative uncorrected distance visual acuity (UDVA) vs preoperative corrected distance visual acuity (CDVA), (B) change of CDVA in terms of numbers of decimal lines, (C) spherical equivalent correction attempted vs achieved, (D) accuracy of spherical equivalent correction, (E) accuracy of refractive astigmatism correction, and (F) stability of postoperative spherical equivalent refraction. D = diopters

One-Year Postoperative Visual Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRK With or Without MMC

Table B:

One-Year Postoperative Visual Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRK With or Without MMC

We observed no significant differences in rate of haze induction between eyes with or without MMC application at any time point postoperatively (Table C [available in the online version of this article], Figure 3). By the third postoperative month, 2+ corneal haze was detected in 2 (2.8%) left eyes compared to 1 (1.4%) right eye (P > .99). Six months postoperatively, the rate of 2+ haze was identical in right and left eyes (1 [1.4%] eye in both groups). At last follow-up, no 2+ corneal haze was detected in either group. Similarly, at the third postoperative month, 1+ haze was observed in 2 (2.8%) left and 1 (1.4%) right eye (P > .99). This haze was cleared in both groups by last follow-up. We detected no haze grade greater than 2+ in any group at any time point of follow-up.

Incidence Rates of Postoperative Haze Induction in Myopic Eyes Undergoing Transepithelial PRK With or Without MMC

Table C:

Incidence Rates of Postoperative Haze Induction in Myopic Eyes Undergoing Transepithelial PRK With or Without MMC

Rates of postoperative haze induction. The figure summarizes rates of haze induction in eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy with (filled bars) or without (unfilled bars) mitomycin C (MMC). At each follow-up time-point, incidence rates of different scales of haze (trace, 1+, or 2+) are illustrated. No eye developed haze greater than 2+.

Figure 3.

Rates of postoperative haze induction. The figure summarizes rates of haze induction in eyes with mild to moderate myopia treated by single-step transepithelial photorefractive keratectomy with (filled bars) or without (unfilled bars) mitomycin C (MMC). At each follow-up time-point, incidence rates of different scales of haze (trace, 1+, or 2+) are illustrated. No eye developed haze greater than 2+.

Except haze induction, we did not encounter any intraoperative or postoperative complications. Until the last visit, we observed no eyes with two or more lines of corrected distance visual acuity loss in either of the study groups. By 48 hours after the surgery, complete corneal reepithelialization was detected in 62 (87.32%) right and 65 (91.55%) left eyes (P = .41). All of the eyes had complete reepithelialization by 72 hours after the surgery. We regularly monitored intraocular pressure of treated eyes during the 12-month follow-up to screen for any potential intraocular pressure rise as a complication of extended steroid use. No case of intraocular pressure rise or cataract induction was detected.

Discussion

In this comparative study on eyes with mild to moderate myopia undergoing single-step transepithelial PRK, there were no significant differences in haze incidence between eyes with or without MMC application at any time point after the surgery. All of the eyes achieved stable refraction 3 months postoperatively. Postoperative refraction, visual acuity, contrast sensitivity, and HOAs were comparable between the two groups of eyes. However, endothelial cell loss and polymegethism were higher among eyes treated with MMC.

The low grade of haze induction regardless of MMC application casts doubt as to whether MMC application prevents haze after single-step transepithelial PRK in mild to moderate myopia. This is different from the results of MMC effects on postoperative haze following other PRK modalities. Less haze was reported in MMC-treated eyes with low and high myopia undergoing LASEK compared with the control group and the level of haze in both groups was low.26 Another study reported lower rates of low-grade haze 6 months postoperatively in eyes with low myopia undergoing PRK with short-time MMC application compared to eyes without MMC while showing no MMC-related cytotoxic effects.3 In support, the efficacy of low (0.002%) and high (0.02%) concentrations of MMC was comparable27 and higher than no MMC application12 in preventing haze in eyes with low myopia undergoing PRK. Thus, there are several differences in both corneal healing process and ensuing haze incidence, as well as indications of MMC application, between single-step transepithelial PRK and other modalities of PRK.

There are several possible reasons for the lower incidence of haze induction in single-step transepithelial PRK compared to other modalities of PRK. Transepithelial laser–assisted ablation of the cornea results in lower keratocyte insults and inflammatory response compared to mechanical or chemical approaches of epithelial removal.28,29 It also produces a smoother and more uniform surface compared to mechanical PRK.30 Furthermore, the reverse sequence of stroma–epithelium ablation in single-step transepithelial PRK promotes a smoothing effect of the epithelium over stromal irregularities. Finally, the shorter duration of this technique attenuates tissue dehydration prior to ablation.18

In this study, promising postoperative visual outcomes along with low degrees of haze induction were achieved in eyes undergoing refined single-step transepithelial PRK with or without MMC application. In the MMC application group, incidences of 2+, 1+, and trace haze 3 months postoperatively were 3%, 3%, and 4%, respectively. These rates are lower than those reported by another study of single-step transepithelial PRK with MMC application, in which incidences of 2+, 1+, and trace hazes by 3 months postoperatively were 2%, 8%, and 30%, respectively.16 Likewise, another study18 of single-step transepithelial PRK with MMC application reported a mean haze score of 0.2 at 1 month postoperatively, which was higher than the corresponding mean haze score of 0.025 in the MMC-treated group in the current study. Based on the similar haze results of the two groups in this study and comparing them with the results of other studies using MMC application, we can conclude that MMC application during single-step transepithelial PRK in mild to moderate myopia may not have a significant effect on the level of postoperative haze induction.

In addition to lower grades of refractive error treated in this study compared to previous studies of single-step transepithelial PRK,16,18 some other differences in intra-surgical and post-ablative measures could explain our overall lower haze rates in both groups of eyes. We considered longer treatment with low-dose topical corticosteroids. Development of clinically significant late haze is mainly attributable to formation of corneal stromal myofibroblasts.31,32 Corticosteroids have inhibitory effects on growth factors needed for development of mature myofibroblasts.32,33 Preventive effects of topical corticosteroids against haze development has been reported in eyes treated by PRK.34 Therefore, longer topical corticosteroid administration could have contributed to our lower haze results. This also could have contributed to timely resolution of the few cases of 2+ haze encountered in this study. We detected no intraocular pressure rise or cataract induction as potential complications of extended corticosteroid use, in line with previous studies that reported lower rates of intraocular pressure rise in eyes treated by loteprednol compared to other topical corticosteroids.35 This safety profile renders loteprednol an appropriate choice for the regimen used in this study.

Ultraviolet exposure could promote haze after PRK. It exacerbates and prolongs the stromal healing process by damaging epithelial cells, increasing keratinocytes, and inducing corneal edema and accumulation of disorganized collagen in the anterior stroma.36 Significant late-onset haze development after PRK has been reported in patients living in regions with high ultraviolet radiation levels.37 The authors recommended using ultra-violet protective eyewear during the first year after PRK, especially when at risk of high ultraviolet exposure (reflection from snow or water, high altitude, or low latitude). Our cases were from different parts of the country, with exposures to ultraviolet index ranging from 2 to 11 during a 1-year period (Table D, available in the online version of this article). This range includes high and extreme categories of ultraviolet exposure, warranting skin and eye protection. Accordingly, we instructed our patients to wear standard sunglasses, which could have contributed to our lower haze rates.

Geographical Characteristics of and Annual Range of UV Index in Cities Where Patients With Myopia Who Underwent Single-Step Transepithelial PRK Keratectomy Inhabited

Table D:

Geographical Characteristics of and Annual Range of UV Index in Cities Where Patients With Myopia Who Underwent Single-Step Transepithelial PRK Keratectomy Inhabited

Furthermore, we used chilled BSS in this study. Thermal insult during excimer laser ablation contributes to further corneal tissue damage and promotes corneal haze after ablation.38 As expected, corneal cooling with chilled BSS was shown to effectively reduce postoperative haze in eyes undergoing PRK modalities.38

MMC-treated eyes in this study showed higher endothelial cell loss and polymegethism compared to the control group. This is in contrast with the results of some studies suggesting the safety of MMC application during PRK.5–8 However, there are experimental and clinical studies supporting our findings about endothelial cytotoxicity of MMC when used in PRK.9,10,39 Controversy over the safety results of MMC could be due to differences in dose and duration of MMC application, follow-up periods, method of PRK, and ethnic characteristics of study samples. Our results are similar to a previous study on Iranian patients undergoing PRK with a similar dose and duration of MMC application.9 In contrast, another study on Iranian patients receiving a shorter duration of MMC application during PRK reported no cytotoxic effects.3 Both dose and duration were suggested to be important correlates of cytotoxicity in rabbit eyes exposed to MMC, whereas dose exerted greater influence compared to duration.40 The current study is the first to report the effects of MMC application following single-step transepithelial PRK on the corneal endothelium. More studies on varied ethnic samples using different MMC regimens following single-step transepithelial PRK are warranted.

We investigated MMC indications in eyes with myopia up to −5.50 D with or without astigmatism (spherical equivalent up to −6.00 D), and corresponding total laser ablation depths below 160 μm. It should be kept in mind that the ablation depth in transepithelial PRK is the sum of epithelial and stromal ablations. It is expectedly higher than PRK for the same level of myopia because the ablation depth in PRK includes only the stromal ablation. Considering this inconsistency in ablation depth among different PRK modalities, degree of myopia rather than ablation depth should be referred to when comparing indications of MMC application among these procedures. We doubted MMC indications following single-step transepithelial PRK in myopia up to −5.50 D (spherical equivalent up to −6.00 D), which differs from the existing consensus regarding its application during PRK.15 In support to our findings, Margo and Munir2 suggested spherical equivalent of greater than 6.00 D, astigmatism of greater than 1.50 D, and myopia of greater than 5.25 D as cut-off points for the risk of corneal haze induction following refractive surgery. A review by Majmudar et al.15 about MMC application during PRK concluded that there is controversy regarding the optimum dosage and duration of MMC application in mild myopia; however, they did not doubt the necessity of MMC application in moderate and high myopia.

Some limitations should be noted in interpreting our findings. Potential influence of topical application of any drug (in this case MMC) on the fellow eye of the same patient could have affected our control group's haze results. Furthermore, more prolonged use of topical corticosteroid in our regimen compared to previous regimens could have modified the haze results obtained in this study. However, the latter is expected to have exerted similar effects on both eyes regardless of the MMC application.

We found that 0.02% MMC application does not have a significant preventive effect on haze induction after single-step transepithelial PRK in mild to moderate myopia (spherical equivalent up to −6.00 D). The postoperative refraction, visual acuity, contrast sensitivity, and HOAs were comparable between our two study groups with and without MMC application. We also showed more endothelial cell toxicity in the MMC-treated eyes, further questioning the use of MMC in this subgroup. More studies on varied ethnical samples and with different MMC regimens are needed to further clarify the role of MMC in single-step transepithelial PRK.

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Preoperative Ophthalmologic Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRKa

ParameterRight EyeLeft EyeP
Ablation depth (μm)122.35 ± 21.50122.90 ± 21.17.88
Optical zone (mm)6.70 ± 0.356.71 ± 0.36.88
Transitional zone (mm)1.15 ± 0.371.14 ± 0.34.87
Corneal central thickness (μm)547.32 ± 37.44546.67 ± 37.3.92
Spherical equivalent (D)−3.20 ± 1.23−3.28 ± 1.22.70
Cylindrical refraction (D)−0.81 ± 0.54−0.77 ± 0.57.67
LogMAR UDVA0.51 ± 0.360.55 ± 0.36.51
LogMAR CDVA−0.05 ± 0.05−0.06 ± 0.05.23
Contrast sensitivity
  Photopic0.95 ± 0.300.89 ± 0.28.22
  Mesopic1.09 ± 0.530.99 ± 0.49.24
Corneal wave-front HOAs (μm)
  Coma0.33 ± 1.530.19 ± 0.10.41
  Trefoil0.15 ± 0.100.14 ± 0.06.47
  Spherical0.23 ± 0.060.23 ± 0.06> .99
  Tetrafoil0.05 ± 0.040.04 ± 0.04.14
Endothelial cell characteristics
  Cell density (cells/mm2)2,863.94 ± 295.142,829.72 ± 301.79.50
  Coefficient of variance30.64 ± 4.9729.68 ± 5.28.27
  Hexagonality (%)59.82 ± 10.5459.58 ± 10.12.89

One-Year Postoperative Visual Parameters of Myopic Eyes Undergoing Single-Step Transepithelial PRK With or Without MMC

ParameterRight Eye (With MMC)Left Eye (Without MMC)P
Spherical equivalent (D)0.01 ± 0.040.01 ± 0.04> .99
Cylindrical refraction (D)−0.01 ± 0.050.15
  ±0.50 D SE predictability (%)99100> .99
  ±1.00 D SE predictability (%)100100> .99
LogMAR UDVA−0.07 ± 0.19−0.10 ± 0.15.30
LogMAR CDVA−0.13 ± 0.05−0.13 ± 0.06> .99
UDVA ≥ 20/20 (%)9597.5.37
≥ 2 lines loss of CDVA (%)00> .99
Contrast sensitivity
  Photopic0.83 ± 0.410.81 ± 0.31.74
  Mesopic0.86 ± 0.390.84 ± 0.28.72
Corneal wavefront HOAs (μm)
  Coma0.18 ± 0.180.21 ± 0.10.52
  Trefoil0.16 ± 0.090.18 ± 0.08.21
  Spherical0.28 ± 0.150.29 ± 0.14.68
  Tetrafoil0.05 ± 0.030.05 ± 0.02> .99
Endothelial cell characteristics
  Cell density loss (%)5.1 ± 4.32.3 ± 2.2< .001
  Coefficient of variance33.12 ± 4.7230.23 ± 5.16.001
  Hexagonality (%)56.43 ± 10.8158.77 ± 9.61.15

Incidence Rates of Postoperative Haze Induction in Myopic Eyes Undergoing Transepithelial PRK With or Without MMC

Haze GradeaRight Eye (With MMC) Follow-up (mo)Left Eye (Without MMC) Follow-up (mo)


1361213612
Trace3 (4.2)2 (2.8)2 (2.8)1 (1.4)3 (4.2)3 (4.2)2 (2.8)1 (1.4)
1+2 (2.8)1 (1.4)0002 (2.8)1 (1.4)0
2+01 (1.4)1 (1.4)002 (2.8)1 (1.4)0
3+00000000
4+00000000
Total7171717171717171

Geographical Characteristics of and Annual Range of UV Index in Cities Where Patients With Myopia Who Underwent Single-Step Transepithelial PRK Keratectomy Inhabited

CityLocation in CountryGeographical IndicesAnnual UV Index Range (hJ/m2)


Latitude (°)Longitude (°)Altitude (m)MinMax
Tehran (capital city)Center35.724841651.3816531,29729
EsfehanCenter32.654627551.66798261,58039
TabrizNorthwest38.09623946.27380131,36628
MashhadNortheast36.419060159.564236997538
ShirazSouth29.591767752.58369821,50849
SanandajWest35.321874846.98616471,53818
ZahedanSoutheast29.45192660.88419831,39439
AhvazSouthwest31.318327248.670618721411
RashtNorthern coast37.268217749.5891233328
Bandar-AbbasSouthern coast27.1737556.2808490610
Authors

From Bina Eye Hospital, Tehran, Iran (SA-M, SS-J, GT, ST); TransPRK Research Group, Tehran, Iran (SA-M, SS-J, GT, ST); Universal Council of Ophthalmology (UCO), Universal Scientific Education and Research Network (USERN), Tehran, Iran (SA-M, SS-J, GT, ST); Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, Crete, Greece (MAG); the Department of Ophthalmology, Faculty of Medicine, University of Athens, Athens, Greece (GDK); and Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland (GDK).

The authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (SA-M, SS-J, MAG, GDK); data collection (SS-J, GT, ST); analysis and interpretation of data (SS-J); writing the manuscript (SA-M, SS-J, GT, ST, MAG, GDK); critical revision of the manuscript (SA-M, SS-J, GT, ST, MAG, GDK); statistical expertise (SS-J); administrative, technical, or material support (SA-M, GDK); supervision (SA-M)

Correspondence: Soheil Adib-Moghaddam, MD, Bina Eye Hospital, Resalat Highway, Tehran 1634764651, Iran. E-mail: Soheil.adibmoghaddam@gmail.com

Received: July 06, 2017
Accepted: April 02, 2018

10.3928/1081597X-20180402-02

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