Journal of Refractive Surgery

Original Article 

The U.S. Army Surface Ablation Study: Comparison of PRK, MMC-PRK, and LASEK in Moderate to High Myopia

Rose K. Sia, MD; Denise S. Ryan, MS; Jayson D. Edwards, MD; Richard D. Stutzman, MD; Kraig S. Bower, MD

Abstract

PURPOSE:

To compare visual outcomes following photorefractive keratectomy (PRK), PRK with mitomycin C (MMC-PRK), and LASEK in moderate and high myopia in military personnel.

METHODS:

This prospective, randomized contralateral eye study included 167 patients 21 years or older with manifest spherical equivalent −5.99 ± 1.40 diopters (D) (range: −3.88 to −9.38 D) randomized to either MMC-PRK or LASEK treatment in their dominant eye and conventional PRK without MMC in the fellow eye. All procedures were performed using the LADARVision 4000 Excimer Laser System (Alcon Surgical Inc., Ft. Worth, TX). High- and low-contrast visual acuities, manifest refraction, endothelial cell count, and corneal haze were evaluated up to 12 months postoperatively.

RESULTS:

At 12 months postoperatively, visual outcomes were comparable among the treatment groups. Corneal haze of any grade was less common in MMC-PRK compared to PRK at 1 month (21.4% vs 31.0%; P < .01) and 3 months (12.8% vs 35.9%; P = .03) postoperatively; it was also less common in MMC-PRK compared to LASEK at 1 month (21.4% vs 55.9%; P < .01), 3 months (12.8% vs 42.4%; P < .01), and 6 months (12.2% vs 36.4%; P = .03) postoperatively. Haze rate (grade 0.5 or higher) was comparable between LASEK and PRK. Clinically significant haze (grade 2 or higher) developed after PRK (4 eyes) and LASEK (2 eyes), but not after MMC-PRK.

CONCLUSIONS:

MMC-PRK showed some benefits in minimizing corneal haze formation. One year after surgery, there was no discernible difference in the postoperative refractive outcomes among the three methods.

[J Refract Surg. 2014;30(4):256–264.]

From Warfighter Refractive Eye Surgery Program and Research Center at Fort Belvoir, Fort Belvoir, Virginia (RKS, DSR); the Department of Ophthalmology, Tulane University, New Orleans, Louisiana (JDE); Ophthalmology Service, Walter Reed National Military Medical Center, Bethesda, Maryland (RDS); and the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland (KSB).

Presented in part at the Association for Research in Vision and Ophthalmology annual meeting; May 2007 and April/May 2008; Ft. Lauderdale, Florida.

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

The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

AUTHOR CONTRIBUTIONS

Study concept and design (KSB); data collection (RKS, DSR, JDE, RDS, KSB); analysis and interpretation of data (RKS, DSR, RDS, KSB); drafting of the manuscript (RKS, JDE, KSB); critical revision of the manuscript (DSR, JDE, RDS, KSB); statistical expertise (RKS); administrative, technical, or material support (DSR); supervision (KSB)

Correspondence: Rose K. Sia, MD, Warfighter Refractive Eye Surgery Program and Research Center at Fort Belvoir, Fort Belvoir Community Hospital, 9300 DeWitt Loop, Fort Belvoir, VA 22060. E-mail: rose.k.sia.ctr@heath.mil

Received: September 25, 2013
Accepted: January 02, 2014
Posted Online: April 04, 2014

Abstract

PURPOSE:

To compare visual outcomes following photorefractive keratectomy (PRK), PRK with mitomycin C (MMC-PRK), and LASEK in moderate and high myopia in military personnel.

METHODS:

This prospective, randomized contralateral eye study included 167 patients 21 years or older with manifest spherical equivalent −5.99 ± 1.40 diopters (D) (range: −3.88 to −9.38 D) randomized to either MMC-PRK or LASEK treatment in their dominant eye and conventional PRK without MMC in the fellow eye. All procedures were performed using the LADARVision 4000 Excimer Laser System (Alcon Surgical Inc., Ft. Worth, TX). High- and low-contrast visual acuities, manifest refraction, endothelial cell count, and corneal haze were evaluated up to 12 months postoperatively.

RESULTS:

At 12 months postoperatively, visual outcomes were comparable among the treatment groups. Corneal haze of any grade was less common in MMC-PRK compared to PRK at 1 month (21.4% vs 31.0%; P < .01) and 3 months (12.8% vs 35.9%; P = .03) postoperatively; it was also less common in MMC-PRK compared to LASEK at 1 month (21.4% vs 55.9%; P < .01), 3 months (12.8% vs 42.4%; P < .01), and 6 months (12.2% vs 36.4%; P = .03) postoperatively. Haze rate (grade 0.5 or higher) was comparable between LASEK and PRK. Clinically significant haze (grade 2 or higher) developed after PRK (4 eyes) and LASEK (2 eyes), but not after MMC-PRK.

CONCLUSIONS:

MMC-PRK showed some benefits in minimizing corneal haze formation. One year after surgery, there was no discernible difference in the postoperative refractive outcomes among the three methods.

[J Refract Surg. 2014;30(4):256–264.]

From Warfighter Refractive Eye Surgery Program and Research Center at Fort Belvoir, Fort Belvoir, Virginia (RKS, DSR); the Department of Ophthalmology, Tulane University, New Orleans, Louisiana (JDE); Ophthalmology Service, Walter Reed National Military Medical Center, Bethesda, Maryland (RDS); and the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland (KSB).

Presented in part at the Association for Research in Vision and Ophthalmology annual meeting; May 2007 and April/May 2008; Ft. Lauderdale, Florida.

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

The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

AUTHOR CONTRIBUTIONS

Study concept and design (KSB); data collection (RKS, DSR, JDE, RDS, KSB); analysis and interpretation of data (RKS, DSR, RDS, KSB); drafting of the manuscript (RKS, JDE, KSB); critical revision of the manuscript (DSR, JDE, RDS, KSB); statistical expertise (RKS); administrative, technical, or material support (DSR); supervision (KSB)

Correspondence: Rose K. Sia, MD, Warfighter Refractive Eye Surgery Program and Research Center at Fort Belvoir, Fort Belvoir Community Hospital, 9300 DeWitt Loop, Fort Belvoir, VA 22060. E-mail: rose.k.sia.ctr@heath.mil

Received: September 25, 2013
Accepted: January 02, 2014
Posted Online: April 04, 2014

The Warfighter Refractive Eye Surgery Program was established in May 2000 by the U.S. Army Medical Command to enhance soldier readiness and reduce dependence on optical corrections such as glasses and contact lenses. Nearly three-quarters of refractive surgery procedures performed between 2000 and 2003 in the U.S. Army were surface ablations, photorefractive keratectomy (PRK) being the predominant procedure.1 This proportion may be even higher in recent years.2 Although PRK and LASIK have favorable postoperative outcomes,3,4 flap-related complications in LASIK pose potential risks in patients who may be predisposed to trauma (eg, military personnel). On the other hand, clinically significant corneal haze and regression are known limitations in PRK, especially with increasing amount of attempted correction.5,6

The intraoperative application of mitomycin C (MMC) during PRK has been shown to reduce the incidence of haze and to improve visual outcomes in high myopia (−6.00 diopters [D] or greater).7,8 Stromal haze and myopic regression have been largely attributed to the wound healing response after laser ablation. MMC acts by inhibiting the activation of keratocytes and induces keratocyte apoptosis in the corneal wound healing process.9,10

LASEK has been advocated as a treatment alternative to expedite visual recovery, minimize pain, and decrease the incidence of haze and regression associated with PRK while negating flap-related and biomechanical complications in LASIK.11,12 A dilute (18% to 20%) alcohol solution is used to separate the epithelial basement membrane attachments from the underlying corneal stroma. The epithelium is then removed from the treatment zone as an intact epithelial flap. It has been hypothesized that the epithelial flap acts as a barrier to inflammatory mediators and cells from the tear film that can lead to an aggravated wound-healing response and haze formation.11,13

To our knowledge, no sizable prospective studies have been published directly comparing LASEK to PRK with and without prophylactic MMC for the correction of moderate to high myopia. This study was conducted to evaluate the outcomes and determine the role of alternative surface ablation techniques in military refractive surgery.

Patients and Methods

This prospective clinical trial was performed at the Center for Refractive Surgery at the Walter Reed Army Medical Center, Washington, DC. The research protocol was reviewed and approved by the Walter Reed Institutional Review Board prior to implementation. This trial was registered at www.clinicaltrials.gov (Clinicaltrials. gov Identifier: NCT00415077). Written informed consent was obtained after counseling the risk and benefits of participation and the study was performed in accordance with the tenets of the Declaration of Helsinki.

A total of 167 active duty U.S. Army personnel, age 21 years or older with moderate to high myopia (defined as manifest spherical equivalent [MSE] of −4.00 D or greater) and corrected distance visual acuity (CDVA) of 20/20 or better in both eyes, were included in the study. All patients demonstrated refractive stability for at least 12 months prior to surgery. Patients were randomized to treatment of their dominant eye with either PRK with mitomycin C (MMC-PRK) or LASEK. The fellow eye underwent conventional PRK without MMC. The contralateral study design was made to allow study groups to be well matched; each eye acted as a control to the fellow randomized eye.

All photoablations were performed using the LADARVision 4000 Excimer Laser System (Alcon Surgical, Inc., Ft. Worth, TX). Treatments were conventional with a 6.5-mm optical zone; no wavefront-guided treatments were performed. The laser was programmed using a standard nomogram and was the same for all groups. All MMC-PRK procedures had a surgeon factor adjustment of −5%, based on previous results with MMC cases on the same laser platform (unpublished data). A 9.0-mm epithelial defect was created using the Amoils rotary brush (Innovative Excimer Solutions, Toronto, Ontario, Canada) in all PRK procedures. In MMC-PRK, a corneal shield soaked with MMC 0.02% was placed on the ablation zone for 60 seconds and then irrigated with chilled balanced salt solution after the photoablation. In LASEK, a 9.0-mm epithelial trephine was used to mark the cornea. Exposure to 20% ethanol for 25 to 30 seconds was used to loosen the epithelium to create an epithelial flap with the hinge located superiorly. After photoablation, the corneal epithelial flap was repositioned, ensuring adequate alignment. Following surgery, topical moxifloxacin 0.5% (Vigamox; Alcon Surgical, Inc.) and ketorolac 0.4% (Acular-LS; Allergan, Inc., Irvine, CA) were applied and a therapeutic bandage contact lens omafilcon A (Proclear; CooperVision, Fairport, NY) was inserted until complete re-epithelialization.

Postoperative medication was the same for all treated eyes: moxifloxacin 0.5%, one drop four times daily for 1 week or until complete re-epithelialization; fluorometholone 0.1%, one drop four times daily for 4 weeks followed by a 6-week taper; carboxymethyl-cellulose 0.5% (Refresh Plus; Allergan, Inc.), one drop four to eight times daily for 2 weeks then as needed; ketorolac 0.4%, one drop up to four times daily for the first 48 hours after surgery as needed for pain, and oxycodone/acetaminophen 5 mg/325 mg orally every 6 hours as needed for postoperative pain.

Patient follow-up was at 1, 4, and 7 days and 1, 3, 6, and 12 months postoperatively. Uncorrected distance visual acuity (UDVA), re-epithelialization, pain, and any complications were assessed at 1, 4, and 7 days postoperatively. Pain was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (severe/worst possible pain). UDVA, CDVA, manifest refraction, small letter contrast test (SLCT), 5% and 25% low-contrast visual acuity (LCVA), and slit-lamp biomicroscopy were assessed at the 1-, 3-, 6-, and 12-month follow-up visits. SLCT was performed using a chart comprising letters of constant, small size (20/25), which vary in contrast, by row, in 0.1 log unit steps.14 LCVA was performed using back-illuminated logMAR charts with 5% and 25% contrast (Precision Vision, Inc., La Salle, IL). Corneal haze was graded as follows: grade 0, totally clear cornea; grade 0.5, trace or faint haze seen only by indirect, broad tangential illumination; grade 1, minimal density seen with difficulty with direct and diffuse examination; grade 2, mild haze easily visible with direct focal slit illumination; grade 3, moderate opacity that partially obscured details of the iris; and grade 4, severe opacity that completely obscured the details of intraocular structures.15 Grade 2 or higher was considered clinically significant. Endothelial cell density was also assessed preoperatively and at 6 and 12 months postoperatively.

Data Analysis

Eyes treated with MMC-PRK or LASEK were compared to contralateral eyes treated with PRK. MMC-PRK was also compared to LASEK after initial analysis showed no significant difference between the two PRK subgroups. Exploratory analysis was done on the cohort of patients with myopia of −6.00 D or greater. Visual outcomes were determined as follows: refractive efficacy was assessed by postoperative UDVA; safety by maintenance of CDVA within one Snellen line; predictability by postoperative MSE; and stability as changes in MSE over time. The 12-month refractive outcomes were presented graphically using the standard format.16 Data analysis was performed using SPSS for Windows version 21.0 (IBM Corporation, Armonk, NY). The Fisher exact test was used to assess differences in visual outcomes and corneal haze rate. Repeated measures analysis of variance was used to determine significant changes in endothelial cell density and contrast sensitivity. The Mann–Whitney test was used to compare early postoperative UDVA and pain scores. Results are presented as mean ± standard deviation. A P value less than .05 was considered statistically significant.

Results

A total of 167 patients, mean age 34.4 ± 7.8 years (range: 21 to 57 years) and 63.5% male (n = 106), were evaluated. Preoperative mean MSE was −5.99 ± 1.40 D (range: −3.88 to −9.38 D). Mean preoperative cylinder was −0.78 ± 0.69 D (range: 0 to −3.25 D). Mean central corneal thickness was 548.8 ± 31.6 μm (range: 475 to 652 μm). Table 1 shows patient demographics and preoperative clinical data according to treatment group. Eighty-four patients underwent contralateral treatment of MMC-PRK and PRK (MMC-PRK/PRK group), whereas 83 patients underwent contralateral treatment of LASEK and PRK (LASEK/PRK group). There were no intraoperative complications reported in any treatment groups.

Preoperative Baseline Characteristics by Treatment Group

Table 1:

Preoperative Baseline Characteristics by Treatment Group

Patient Follow-up

One hundred sixty-five (98.8%; 84 in the MMC-PRK/PRK group, 81 in the LASEK/PRK group) patients were observed at 1 month, 160 (95.8%; 82 in the MMC-PRK/PRK group, 78 in the LASEK/PRK group) at 3 months, 152 (91.0%; 77 in the MMC-PRK/PRK group, 75 in the LASEK/PRK group) at 6 months, and 132 (79.0%; 66 in the MMC-PRK/PRK group, 66 in the LASEK/PRK group) at 12 months. There was no significant difference in age, gender, or baseline MSE, UDVA, and CDVA between initial patients and those observed at the time periods studied.

Early Postoperative Healing

The pain scores in PRK-treated eyes compared to either MMC-PRK– or LASEK-treated fellow eyes were comparable as reported by patients at 1, 4, and 7 days postoperatively (Table 2). There was also no significant difference in postoperative pain scores between MMC-PRK– and LASEK-treated eyes at 1 (P = .12), 4 (P = .96), and 7 (P = .17) days postoperatively. Complete corneal re-epithelialization was observed at 4 days postoperatively in 91.1% of MMC-PRK–treated eyes compared to 81.0% of PRK-treated eyes (P = .11) and in 73.8% of LASEK-treated eyes versus 81.3% of PRK-treated eyes (P = .34). A significantly greater percentage of eyes were fully healed 4 days after MMC-PRK compared to LASEK (P = .01). Corneal epithelium was fully healed at 7 days postoperatively in 98.8% of MMC-PRK–treated eyes versus 97.5% of PRK-treated (P = .99) eyes and 97.6% of LASEK-treated eyes compared to 100.0% of PRK-treated eyes (P = .50). Delayed re-epithelialization was observed in 1 MMC-PRK–, 2 LASEK- and 2 PRK-treated eyes requiring additional follow-up. All other treated eyes were completely healed by 10 days postoperatively. LASEK was associated with significantly worse UDVA compared to PRK at 1 day (logMAR 0.46 [Snellen 20/60+1] vs logMAR 0.34 [Snellen 20/40−2]; P < .01) and 4 days (logMAR 0.32 [Snellen 20/40−1] vs logMAR 0.25 [Snellen 20/32−2]; P = .02) postoperatively; LASEK also had worse UDVA compared to MMC-PRK at 1 day (logMAR 0.46 [Snellen 20/60+1] vs logMAR 0.36 [Snellen 20/50+2; P = .01]) postoperatively. There were no other significant differences in UDVA in the early postoperative period.

Mean Postoperative Pain Scores by Treatment Group

Table 2:

Mean Postoperative Pain Scores by Treatment Group

Efficacy

The number of eyes achieving UDVA of 20/20 or better was comparable between MMC-PRK and PRK and between LASEK and PRK (Table 3). UDVA of 20/20 or better was less common in MMC-PRK–treated eyes compared to LASEK-treated eyes at 1 month postoperatively (44% vs 63%, respectively; P = .02) but not at other time periods. Figure 1 compares the distribution of UDVA at 12 months to preoperative CDVA in the MMC-PRK/PRK and LASEK/PRK treatment groups.

No. of Eyes Achieving UDVA of 20/20 or Better Postoperatively

Table 3:

No. of Eyes Achieving UDVA of 20/20 or Better Postoperatively

Distribution of uncorrected distance visual acuity (UDVA) at 12 months against distribution of preoperative corrected distance visual acuity (CDVA) in the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) LASEK/PRK treatment groups.

Figure 1.

Distribution of uncorrected distance visual acuity (UDVA) at 12 months against distribution of preoperative corrected distance visual acuity (CDVA) in the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) LASEK/PRK treatment groups.

Safety

For the MMC-PRK/PRK treatment group, a loss of two or more lines of CDVA was observed in 4 (4.9%) MMC-PRK–treated eyes compared to 3 (3.7%) PRK-treated eyes at 1 month (P = .99) and 1 (1.3%) MMC-PRK–treated eye at 3 months. For the LASEK/PRK treatment group, a loss of two or more lines of CDVA was seen in 2 (2.5%) LASEK-treated eyes versus 4 (4.9%) PRK-treated eyes at 1 month (P = .68) and 1 (1.4%) LASEK-treated eye versus 2 (2.7%) PRK-treated eyes at 6 months (P = .99). In the LASEK/PRK treatment group, 1 (1.5%) PRK-treated eye lost three CDVA lines from baseline at 12 months due to grade 2 corneal haze. Corneal scraping and MMC application resulted in the resolution of haze and improvement of UDVA to 20/15. Safety outcomes between MMC-PRK and LASEK were comparable. Figure 2 shows the change in CDVA from baseline in PRK-treated compared to MMC-PRK– and LASEK-treated eyes at 12 months postoperatively.

Change in corrected distance visual acuity (CDVA) from baseline in photorefractive keratectomy (PRK) compared to (A) mitomycin C photorefractive keratectomy (MMC-PRK) and (B) LASEK-treated eyes at 12 months postoperatively.

Figure 2.

Change in corrected distance visual acuity (CDVA) from baseline in photorefractive keratectomy (PRK) compared to (A) mitomycin C photorefractive keratectomy (MMC-PRK) and (B) LASEK-treated eyes at 12 months postoperatively.

Predictability

MSE within 0.50 D of emmetropia was more common at 1 month after MMC-PRK compared to PRK (P = .03). There was no significant difference between MMC-PRK and PRK at other time periods. LASEK versus PRK results were comparable (Table 4). There was no statistically significant difference between MMC-PRK and LASEK. Figure 3 shows the distribution of 12-month postoperative MSE by treatment group.

No. of Eyes With Manifest Spherical Equivalent Within 0.50 D of Emmetropia Postoperatively

Table 4:

No. of Eyes With Manifest Spherical Equivalent Within 0.50 D of Emmetropia Postoperatively

Distribution of manifest spherical equivalent (MSE) at 12 months postoperative in the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) LASEK/PRK treatment groups.

Figure 3.

Distribution of manifest spherical equivalent (MSE) at 12 months postoperative in the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) LASEK/PRK treatment groups.

Stability

Between the 6- and 12-month periods, changes in MSE were within 0.50 D in 54 (81.8%) MMC-PRK–treated eyes compared to 51 (78.5%) PRK-treated eyes (P = .67) and 53 (82.8%) LASEK-treated eyes versus 53 (82.8%) PRK-treated eyes (P = .99). There was no significant difference between MMC-PRK– and LASEK-treated eyes. Figure 4 shows the mean MSE preoperatively up to the 12-month postoperative period for the MMC-PRK/PRK and LASEK/PRK treatment groups.

Mean manifest spherical equivalent (MSE) from preoperative up to 12 months postoperatively for the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) PRK/LASEK treatment groups.

Figure 4.

Mean manifest spherical equivalent (MSE) from preoperative up to 12 months postoperatively for the (A) mitomycin C photorefractive keratectomy (MMC-PRK/PRK) and (B) PRK/LASEK treatment groups.

Visual Performance

There was a statistically significant decrease in SLCT and 5% and 25% LCVA in patients undergoing MMC-PRK, LASEK, and PRK. All parameters improved to preoperative baseline by 6 months after MMC-PRK and PRK. After LASEK, SLCT and 25% LCVA recovered as early as 3 months postoperatively, whereas 5% LCVA returned to baseline 6 months postoperatively (Figure 5). MMC-PRK was not significantly different compared to PRK in terms of SLCT (P = .57), 5% LCVA (P = .72), and 25% LCVA (P = .61) over time. LASEK and PRK were also statistically comparable (SLCT, P = .57; 5% LCVA, P = .53; and 25% LCVA, P = .80). There was a significant difference between MMC-PRK and LASEK in SLCT (P = .02) but not in 5% LCVA (P = .19) and 25% LCVA (P = .40).

Postoperative (A) small letter contrast test (SLCT) (logCS), positive shift equals improvement, (B) 5% low contrast visual acuities (LCVA) (logMAR), negative shift equals improvement, and (C) 25% LCVA (logMAR), negative shift equals improvement.

Figure 5.

Postoperative (A) small letter contrast test (SLCT) (logCS), positive shift equals improvement, (B) 5% low contrast visual acuities (LCVA) (logMAR), negative shift equals improvement, and (C) 25% LCVA (logMAR), negative shift equals improvement.

Corneal Haze

There was a general progressive clearing of corneal haze in all treatment groups. Figure 6 shows the distribution of corneal haze scores at different times. The number of eyes with corneal haze of any grade after MMC-PRK was comparable to that after PRK except at 3 and 6 months postoperatively when corneal haze was less common in MMC-PRK compared to PRK (P < .01 and .03, respectively). There was no significant difference between LASEK and PRK. Compared to MMC-PRK, the rate of corneal haze (grade 0.5 or higher) was significantly higher after LASEK at 1, 3, and 6 months postoperatively (P < .01). Five patients were observed to have clinically significant haze (grade 2 or higher) during the study period. Patient 1 had a grade 2 corneal haze on the LASEK-treated eye and grade 0.5 haze on contralateral PRK-treated eyes at 1 month. Postoperative LASEK corneal haze eventually resolved after 1 month with topical prednisolone. Patient 2 had grade 2 haze at 3 months that persisted to 6 months after PRK due to poor medication compliance, whereas the contralateral eye showed no sign of any haze formation after MMC-PRK. This patient was given topical prednisolone but was lost to follow-up examination. Patient 3 developed bilateral grade 2 corneal haze 6 months after LASEK and PRK. Patient 4 developed a central reticulate haze 6 months after PRK, whereas patient 5 had grade 2 haze 12 months after PRK. No stromal haze was observed in the contralateral eye of patients 4 and 5 after MMC-PRK and LASEK. Patients 3, 4, and 5 underwent mechanical corneal scraping and application of MMC 0.02% for 1 minute. Postoperative medications included prednisolone acetate 1% (Pred Forte; Allergan, Inc.) four times a day for 1 week, then tapered for 3 weeks. All cases resulted in resolution of haze and improvement of UDVA to 20/30 or better.

Distribution of corneal haze scores among the treatment groups up to 12 months postoperatively.

Figure 6.

Distribution of corneal haze scores among the treatment groups up to 12 months postoperatively.

Endothelial Cell Density

Endothelial cell density did not change significantly at 6 and 12 months postoperatively from baseline in eyes that underwent MMC-PRK, LASEK, or PRK (Table 5).

Mean Endothelial Cell Density Over Time

Table 5:

Mean Endothelial Cell Density Over Time

Myopia of −6.00 D or Greater

Forty-two MMC-PRK–and PRK-treated and 35 LASEK-and PRK-treated patients with mean MSE of −6.85 ± 1.00 D (range: −6.00 to −9.38 D) were included in the subset analysis. Comparing PRK to either MMC-PRK or LASEK, there was no significant difference in the number of eyes with UDVA of 20/20 or better, MSE ±0.50 D of emmetropia, CDVA within one line from baseline, and MSE change within 0.50 D between 6 and 12 months postoperatively. However, there was a significantly greater percentage achieving UDVA of 20/20 or better in MMC-PRK (92.7%) compared to LASEK (73.5%) only at 6 months postoperatively (P = .03). The incidence of corneal haze of any grade was significantly lower in MMC-PRK versus PRK at 3 months postoperatively (12.8% MMC-PRK, 35.9% PRK; P = .03) but not at other times. Haze rate was comparable between LASEK and PRK. Grade 0.5 haze or greater was significantly less common after MMC-PRK compared to LASEK at 1 month (21.4% MMC-PRK, 55.9% LASEK; P < .01), 3 months (12.8% MMC-PRK, 42.4% LASEK; P < .01), and 6 months (12.2% MMC-PRK, 36.4% LASEK; P = .03) postoperatively.

Discussion

Laser refractive surgery is the preferred method of vision correction on the modern battlefield. It has been enthusiastically supported through the Warfighter Refractive Eye Surgery Program by soldiers, units, and commanders because of its impact on mission readiness. Because of the unique operational demand in the military service, surface ablation is still the procedure of choice for soldiers, especially those who are combat-bound. Among the surface ablation techniques, PRK is still the predominant procedure. PRK has been proven safe and effective for treatment of refractive errors.17,18 However, one distinct disadvantage of PRK is the increased likelihood of postoperative corneal haze that can decrease visual acuity and increase night vision disturbances such as glare disability and reduced contrast sensitivity.19,20 Alternative surface ablation techniques including LASEK and the use of MMC in conjunction with PRK were developed with the goal of overcoming the disadvantages of PRK associated with correction of high refractive errors, namely corneal haze and regression.

In the current study, we evaluated MMC-PRK and LASEK in comparison to PRK in treating moderate to high degrees of myopia. During the early postoperative period, pain was generally mild to absent. LASEK did not seem to offer any advantage over PRK in terms of pain mitigation, similar to the previous work of Pirouzian et al., who did not find any significant difference in early postoperative subjective pain in their contralateral eye study comparing LASEK and PRK.21

Most corneal epithelia were healed 4 days after surgery, with a significantly greater percentage after MMC-PRK than LASEK (91.1% vs 73.8%, respectively; P = .01). Delayed re-epithelialization was observed after MMC-PRK (1 eye), LASEK (2 eyes), and PRK (1 eye). Although there were reports of dose-dependent effects of MMC on epithelial healing,22,23 delayed re-epithelialization associated with MMC use in clinical studies was rare.8,24 The effect of ethanol on the corneal epithelium was also found to be dose- and time-dependent because higher doses or longer exposure times could lead to cell death.25 This may defeat the purpose of retaining the epithelial flap to suppress the epithelial cell–stromal wound reaction in LASEK, because it requires the flap epithelial cells to be vital at the time of repositioning.26 With decreased epithelial cell viability and integrity due to alcohol exposure, the flap may not adhere and recover in the same way as a newly deposited and formed epithelium in PRK-treated eyes.21,27 Moreover, Taneri et al.28 speculated that the devitalized epithelial cells in the flap may become opaque, thus compromising vision in the early postoperative period. This and the tendency of epithelial closure to be unpredictable in LASEK may help explain why we found UDVA to be worse in LASEK than either MMC-PRK or PRK for up to 4 days postoperatively.

We also did not find any significant change in the corneal endothelial cell density over the 12-month period following MMC-PRK, LASEK, and PRK. Our findings seemed to suggest that a brief exposure to 0.02% MMC or 20% ethanol did not have any adverse effect on the corneal endothelium; however, the lasting impact cannot be inferred from this study.

High myopic correction requiring deeper ablation is the most common predisposing factor in corneal haze development in PRK.29 In this study, postoperative corneal haze of any grade was observed in all treatment groups. Corneal haze (grade 0.5 or higher) was seen less in MMC-PRK–treated eyes compared to PRK- and LASEK-treated eyes up to 6 months postoperatively. It was previously suggested that prophylactic MMC may induce optimum wound healing modulation, thus inhibiting haze formation after a surface ablation procedure.7,8,22 Nonetheless, it is still recommended that MMC should be used judiciously because the long-term effects remain unproved.10 The incidence of clinically significant haze (grade 2 or higher) was low in this study. Only 5 patients (4 PRK eyes and 2 LASEK eyes), including one with bilateral involvement after LASEK/PRK, were observed to have grade 2 haze. Because of this, no associations could be made between factors such as surface ablation technique, age, sex, epithelial healing, and the development of stromal haze significant enough to alter visual acuity and function.

Visual outcomes following MMC-PRK, LASEK, and PRK were generally favorable and comparable. A significant but transient decrease in contrast sensitivity after MMC-PRK, LASEK, and PRK was observed in this study. Visual performance on SLCT and 5% and 25% LCVA were statistically comparable over time in MMC-PRK versus PRK and LASEK versus PRK. LASEK seemed to outperform MMC-PRK on SLCT but not on 5% and 25% LCVA. The contrast sensitivity findings are particularly important in a military setting. Military operations often occur in adverse environments with diminished light conditions such as night, rain, smoke, or fog and operational demands include the use of devices such as protective masks and night vision goggles.30 A significant loss of visual performance after refractive surgery may potentially impact military tasks performed under low-light settings.

Due to the unanticipated change in laser platform, the study was terminated early with only 167 of the planned 480 participants enrolled. The potential confounding effect of a major change in laser platform prompted the closure to study enrollment. Because of this, we were not able to evaluate the surgical techniques according to the degree of myopia. Nevertheless, we performed a small subset analysis of patients with high myopic error (−6.00 D or greater) because this subgroup was traditionally thought to benefit from the modified procedures. Exploratory analysis revealed no clear advantage of the modified procedures versus standard PRK. However, it did appear MMC-PRK facilitated lower haze rate in this subgroup compared to LASEK and PRK.

To the best of our knowledge, this is the largest prospective study directly comparing PRK to alternative techniques such as the use of prophylactic MMC and LASEK in treating moderate to high myopia. Our study showed MMC-PRK was better in terms of refractive predictability only at 1 month postoperatively compared to PRK. Compared to MMC-PRK, LASEK was associated with slower visual recovery and epithelial healing in the early postoperative period, but was superior in refractive efficacy at 1 month postoperatively and performed better on small letter, low contrast targets over time. Postoperative corneal haze formation was seen less in MMC-PRK than in LASEK and PRK up to 6 months postoperatively. Clinically significant corneal haze was uncommon in our study.

MMC-PRK offered some advantages in minimizing postoperative haze formation and preserving corneal transparency in predisposed eyes. Our study found few differences at specific time periods, but the refractive outcomes were equally favorable among the three techniques 1 year after surgery.

References

  1. Hammond MD, Madigan WP Jr, Bower KS. Refractive surgery in the United States Army, 2000–2003. Ophthalmology. 2005;112:184–190. doi:10.1016/j.ophtha.2004.08.014 [CrossRef]
  2. Trattler WB, Barnes SD. Current trends in advanced surface ablation. Curr Opin Ophthalmol. 2008;19:330–334. doi:10.1097/ICU.0b013e3283034210 [CrossRef]
  3. Tole DM, McCarty DJ, Couper T, Taylor HR. Comparison of laser in situ keratomileusis and photorefractive keratectomy for the correction of myopia of −6.00 diopters or less: Melbourne Excimer Laser Group. J Refract Surg. 2001;17:46–54.
  4. Ang EK, Couper T, Dirani M, Vajpayee RB, Baird PN. Outcomes of laser refractive surgery for myopia. J Cataract Refract Surg. 2009;35:921–933. doi:10.1016/j.jcrs.2009.02.013 [CrossRef]
  5. Møller-Pedersen T, Cavanagh HD, Petroll WM, Jester JV. Corneal haze development after PRK is regulated by volume of stromal tissue removal. Cornea. 1998;17:627–639. doi:10.1097/00003226-199811000-00011 [CrossRef]
  6. Kuo IC, Lee SM, Hwang DG. Late-onset corneal haze and myopic regression after photorefractive keratectomy (PRK). Cornea. 2004;23:350–355. doi:10.1097/00003226-200405000-00007 [CrossRef]
  7. Carones F, Vigo L, Scandola E, Vacchini L. Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after photorefractive keratectomy. J Cataract Refract Surg. 2002;28:2088–2095. doi:10.1016/S0886-3350(02)01701-7 [CrossRef]
  8. Gambato C, Ghirlando A, Moretto E, Busato F, Midena E. Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes. Ophthalmology. 2005;112:208–218. doi:10.1016/j.ophtha.2004.07.035 [CrossRef]
  9. Kim TI, Pak JH, Lee SY, Tchah H. Mitomycin C induced reduction of keratocytes and fibroblasts after photorefractive keratectomy. Invest Ophthalmol Vis Sci. 2004;45:2978–2984. doi:10.1167/iovs.04-0070 [CrossRef]
  10. Netto MV, Mohan RR, Sinha S, Sharma A, Gupta PC, Wilson SE. Effect of prophylactic and therapeutic mitomycin C on corneal apoptosis, cellular proliferation, haze, and long-term keratocyte density in rabbits. J Refract Surg. 2006;22:562–574.
  11. Taneri S, Weisberg M, Azar DT. Surface ablation techniques. J Cataract Refract Surg. 2011;37:392–408. doi:10.1016/j.jcrs.2010.11.013 [CrossRef]
  12. Azar DT, Ang RT, Lee JB, et al. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol. 2001;12:323–328. doi:10.1097/00055735-200108000-00014 [CrossRef]
  13. Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg. 2001;27:565–570. doi:10.1016/S0886-3350(00)00880-4 [CrossRef]
  14. Rabin J, Wicks J. Measuring resolution in the contrast domain: the small letter contrast test. Optom Vis Sci. 1996;73:398–403. doi:10.1097/00006324-199606000-00007 [CrossRef]
  15. Siganos DS, Katsanevaki VJ, Pallikaris IG. Correlation of subepithelial haze and refractive regression 1 month after photorefractive keratectomy for myopia. J Refract Surg. 1999;15:338–342.
  16. Reinstein DZ, Waring GO III, . Graphic reporting of outcomes of refractive surgery. J Refract Surg. 2009;25:975–978. doi:10.3928/1081597X-20091016-01 [CrossRef]
  17. Hersh PS, Stulting RD, Steinert RF, et al. Results of phase III excimer laser photorefractive keratectomy for myopia. The Summit PRK Study Group. Ophthalmology. 1997;104:1535–1553. doi:10.1016/S0161-6420(97)30073-6 [CrossRef]
  18. Shojaei A, Mohammad-Rabei H, Eslani M, Elahi B, Noorizadeh F. Long-term evaluation of complications and results of photorefractive keratectomy in myopia: an 8-year follow-up. Cornea. 2009;28:304–310. doi:10.1097/ICO.0b013e3181896767 [CrossRef]
  19. Fan-Paul NI, Li J, Miller JS, Florakis GJ. Night vision disturbances after corneal refractive surgery. Surv Ophthalmol. 2002;47:533–546. doi:10.1016/S0039-6257(02)00350-8 [CrossRef]
  20. Niesen U, Businger U, Hartmann P, Senn P, Schipper I. Glare sensitivity and visual acuity after excimer laser photorefractive keratectomy for myopia. Br J Ophthalmol. 1997;81:136–140. doi:10.1136/bjo.81.2.136 [CrossRef]
  21. Pirouzian A, Thornton JA, Ngo S. A randomized prospective clinical trial comparing laser subepithelial keratomileusis and photorefractive keratectomy. Arch Ophthalmol. 2004;122:11–16. doi:10.1001/archopht.122.1.11 [CrossRef]
  22. 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;32:1741–1747. doi:10.1016/j.jcrs.2006.05.014 [CrossRef]
  23. Chang SW. Early corneal edema following topical application of mitomycin-C. J Cataract Refract Surg. 2004;30:1742–1750. doi:10.1016/j.jcrs.2003.12.044 [CrossRef]
  24. Leccisotti A. Mitomycin C in photorefractive keratectomy: effect on epithelialization and predictability. Cornea. 2008;27:288–291. doi:10.1097/ICO.0b013e31815c5a51 [CrossRef]
  25. Chen CC, Chang JH, Lee JB, Javier J, Azar DT. Human corneal epithelial cell viability and morphology after dilute alcohol exposure. Invest Ophthalmol Vis Sci. 2002;43:2593–2602.
  26. Gabler B, Winkler von Mohrenfels C, Dreiss AK, Marshall J, Lohmann CP. Vitality of epithelial cells after alcohol exposure during laser-assisted subepithelial keratectomy flap preparation. J Cataract Refract Surg. 2002;28:1841–1846. doi:10.1016/S0886-3350(02)01486-4 [CrossRef]
  27. Ghanem VC, Souza GC, Souza DC, Viese JM, Weber SL, Kara-José N. PRK and butterfly LASEK: prospective, randomized, contralateral eye comparison of epithelial healing and ocular discomfort. J Refract Surg. 2008;24:591–599.
  28. Taneri S, Oehler S, Koch J, Azar D. Effect of repositioning or discarding the epithelial flap in laser-assisted subepithelial keratectomy and epithelial laser in situ keratomileusis. J Cataract Refract Surg. 2011;37:1832–1846. doi:10.1016/j.jcrs.2011.05.026 [CrossRef]
  29. O’Keefe M, Kirwan C. Laser epithelial keratomileusis in 2010: a review. Clin Experiment Ophthalmol. 2010;38:183–191. doi:10.1111/j.1442-9071.2010.02198.x [CrossRef]
  30. Subramanian PS, O’Kane B, Stefanik R, et al. Visual performance with night vision goggles after photorefractive keratectomy for myopia. Ophthalmology. 2003;110:525–530. doi:10.1016/S0161-6420(02)01763-3 [CrossRef]

Preoperative Baseline Characteristics by Treatment Group

ParameterMMC-PRK/PRKLASEK/PRKPa
Age (y)33.2 ± 7.335.7 ± 8.0.38b
Sex (% male)65.561.4.63c
MMC-PRKPRKLASEKPRK




Sphere (D) (range)−5.74 ± 1.46 (−3.25 to −9.25)−5.69 ± 1.36 (−3.50 to −9.00)−5.49 ± 1.40 (−3.25 to −9.25)−5.47 ± 1.48 (−2.75 to −9.00).54
Cylinder (D) (range)−0.76 ± 0.71 (0 to −3.25)−0.83 ± 0.69 (0 to −3.25)−0.71 ± 0.63 (0 to −2.75)−0.83 ± 0.71 (0 to −2.75).61
MSE (D) (range)−6.11 ± 1.42 (−3.88 to −9.38)−6.10 ± 1.38 (−4.00 to −9.38)−5.85 ± 1.38 (−4.00 to −9.25)−5.89 ± 1.42 (−4.00 to −9.25).48
Ablation depth (μm) (range)83.2 ± 16.2 (55.8 to 129.3)87.3 ± 17.2 (58.0 to 143.6)83.3 ± 15.9 (52.5 to 114.0)84.1 ± 16.4 (55.8 to 120.2).34
UDVA (logMAR, Snellen)1.74 ± 0.35 (20/1000)1.72 ± 0.36 (20/1000)1.63 ± 0.37 (20/900)1.67 ± 0.36 (20/900).19
CDVA (logMAR, Snellen)−0.09 ± 0.05 (20/16)−0.09 ± 0.05 (20/16)−0.10 ± 0.04 (20/16)−0.10 ± 0.05 (20/16).50
5% LCVA (logMAR, Snellen)0.37 ± 0.17 (20/50)0.35 ± 0.15 (20/50)0.33 ± 0.13 (20/40)0.34 ± 0.13 (20/40).50
25% LCVA (logMAR, Snellen)0.38 ± 0.13 (20/50)0.37 ±0.12 (20/50)0.37 ± 0.11 (20/50)0.37 ± 0.11 (20/50).96
SLCT (logCS)0.39 ± 0.170.39 ± 0.160.41 ± 0.160.41 ± 0.14.62
CCT (μm)549.5 ± 26.9551.9 ± 29.1546.4 ± 35.7547.5 ± 34.5.70
ECD (cells/mm2)2929 ± 3352906 ± 3182811 ± 3412873 ± 386.15

Mean Postoperative Pain Scores by Treatment Group

Parameter1 Day4 Days7 Days
MMC-PRK (SD)1.60 ± 2.60.67 ± 1.790.01 ± 0.11
PRK (SD)1.56 ± 2.490.51 ± 1.480.12 ± 0.71
P.97.77.31
LASEK (SD)1.00 ± 2.190.63 ± 1.810.13 ± 0.64
PRK (SD)1.23 ± 2.280.54 ± 1.760.01 ± 0.11
P.52.65.17

No. of Eyes Achieving UDVA of 20/20 or Better Postoperatively

Parameter1 Month3 Months6 Months12 Months
MMC-PRK (%)37 (44.0)61 (76.2)72 (93.5)64 (97.0)
PRK (%)50 (59.5)71 (86.6)69 (89.6)63 (96.9)
P.06.08.56.99
LASEK (%)51 (63.0)64 (82.1)64 (85.3)60 (90.9)
PRK (%)40 (49.4)60 (76.2)64 (85.3)61 (92.4)
P.11.55.99.99

No. of Eyes With Manifest Spherical Equivalent Within 0.50 D of Emmetropia Postoperatively

Parameter1 Month3 Months6 Months12 Months
MMC-PRK (%)49 (58.3)52 (63.4)63 (81.8)55 (83.3)
PRK (%)34 (40.5)52 (63.4)56 (72.7)55 (84.6)
P.03.99.25.99
LASEK (%)40 (48.8)45 (57.7)51 (68.0)52 (78.8)
PRK (%)35 (42.7)43 (55.1)47 (62.7)50 (75.8)
P.35.87.61.84

Mean Endothelial Cell Density Over Time

ParameterPreoperative6 Months12 MonthsP
MMC-PRK (SD)2,914 ± 3522,910 ± 3072,859 ± 298.27
LASEK (SD)2,787 ± 3292,783 ± 3392,860 ± 407.06
PRK (SD)2,870 ± 3752,833 ± 3262,828 ± 345.22

10.3928/1081597X-20140320-04

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