Predictors of myopic photorefractive keratectomy retreatment

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ARTICLE

Predictors of myopic photorefractive keratectomy retreatment Russell Pokroy, MD, Michael Mimouni, MD, Tzahi Sela, BSc, Gur Munzer, BSc, Igor Kaiserman, MD, MSc, MHA

Purpose: To determine the factors associated with retreatment after photorefractive keratectomy (PRK) in myopic eyes.

Setting: Care-Vision Laser Centers, Tel-Aviv, Israel. Design: Retrospective cohort study. Methods: A large database on myopic PRK with mitomycin-C (MMC) performed from 2005 to 2012 was studied. Patients were divided into 2 groups according to whether they had retreatment. Multiple preoperative and intraoperative parameters were analyzed for association with retreatment. Results: A total of 9699 eyes of 9699 consecutive patients were studied. The mean age was 25.9 years G 7.3 (SD); 54.1% were men. The mean preoperative subjective spherical equivalent and astigmatism were 4.30 G 2.18 diopters (D) (range 0.5 to 13.0 D) and 0.77 G 0.83 D (range 0 to 6.0 D), respectively.

ince the first clinical photorefractive keratectomy (PRK) treatment was performed in the late 1980s, there have been significant improvements. The transition from broad-beam to flying-spot lasers along with pupil tracking, iris recognition, wavefront-guided ablations, application of mitomycin-C (MMC), improved nomograms, improved preoperative assessment, and collective surgical experience have contributed to the improved refractive outcomes of myopic PRK.1 The incidence of retreatment surgery, also known as enhancement, is a key parameter used by refractive surgeons to assess their surgical success. Two relatively recent studies showed a decrease from the retreatment rates of the 1990s.2,3 The decrease is thought to be due to increased surgeon experience and improvements in technology, as mentioned above. However, the modern PRK era has seen an increase in patient understanding of refractive surgery and raised expectations for good refractive outcomes, which may increase the retreatment rate. Few studies

S

Two hundred twenty-three eyes (2.30%) were retreated. The 2-year retreatment rate decreased from 42 (6.17%) for primary PRK treatments done in 2005 to 2 (0.10%) for primary PRK done in 2012 (R2 Z 0.79, P < .001). Multiple binary logistic regression analysis showed that transepithelial PRK, astigmatism equal to or higher than 3.5 D, and surgeon factor significantly increased the odds of retreatment. Additional parameters significant on univariate analysis alone included age older than 40 years, low preoperative sphere, maximum ablation depth less than 45 mm, preoperative corrected distance visual acuity better than 20/20, MMC application longer than 40 seconds, and optical ablation zone smaller than 7.0 mm.

Conclusion: The retreatment incidence of PRK has continued to decrease. High astigmatism and transepithelial PRK were associated with increased myopic PRK retreatment rates. J Cataract Refract Surg 2017; 43:825–832 Q 2017 ASCRS and ESCRS

have looked at recent myopic PRK retreatment rates. We performed this study to assess retreatment incidence and risk factors in recent years, which incorporates significant collective and individual surgeon experience and technological advances as well as increased patient expectations. PATIENTS AND METHODS The data for the study were collected and analyzed in accordance with the policies of the Institutional Review Board of the Barzilai Medical Center and the tenets of the Declaration of Helsinki. This retrospective study included the right eyes of consecutive patients who had PRK between January 2005 and December 2012 at Care-Vision Laser Centers, Tel-Aviv, Israel. Five high-volume surgeons performed the surgeries using standardized protocols. Inclusion criteria were age greater than 18 years; a stable preoperative refraction for at least 12 months; intraocular pressure (IOP) less than 21 mm Hg; a period without wearing contact lenses (more than 2 weeks for rigid contact lenses and more than 4 days for soft contact lenses); and no history of autoimmune disease, diabetes, or ocular surgery. Since refraction and vision after PRK often require 2 to 3 months to stabilize, eyes having retreatment surgery

Submitted: November 22, 2016 | Final revision submitted: January 2, 2017 | Accepted: February 28, 2017 From the Department of Ophthalmology (Pokroy), Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Care-Vision Laser Centers (Sela, Munzer, Kaiserman), Tel-Aviv, the Department of Ophthalmology (Mimouni), Rambam Health Care Campus, Haifa, and the Department of Ophthalmology (Kaiserman), Barzilai Medical Center, Ashkelon, and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba, Israel. Corresponding author: Russell Pokroy, MD, Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, 70300, Israel. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.

0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.06.001

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within 90 days were excluded from the analysis. Intended monovision cases were excluded. The choice between PRK and laser in situ keratomileusis (LASIK) was made by the operating surgeon based on each patient’s parameters. Data Collection The medical files of all eligible patients were reviewed and the following demographic and preoperative information extracted: age, sex, date of surgery, dominant eye, central corneal thickness (CCT) (Pacscan Plus, Sonomed Escalon), subjective sphere (associated with minus cylinder), subjective spherical equivalent (SE), subjective minus cylinder power and axis (with the rule was defined as within 22.5 degrees of the horizontal, against the rule as within 22.5 degrees of the vertical, and oblique as the intermediary 45 degrees),4 mean keratometric (K) power (Placido disk corneal topography), minimum K power, maximum K power, uncorrected (UDVA) and corrected (CDVA) distance visual acuities. The following intraoperative information was also extracted: operating room humidity, operating room temperature, epithelial removal technique (alcohol-assisted mechanical or transepithelial PRK), optical zone size, maximum ablation depth, MMC application time, the involved eye (right or left), and the surgeon’s name. Surgical Technique The PRK was consistent in the study eyes with the exception of epithelial removal, for which 1 of 2 techniques was used. One drop of a topical anesthetic (benoxinate hydrochloride 0.4%) was instilled in the conjunctival fornix of the eye prior to surgery, after which a lid speculum was inserted. Epithelial removal was performed mechanically after a 15-second exposure to 20% ethyl alcohol. Alternatively, epithelial removal was facilitated using the phototherapeutic mode of the excimer laser (transepithelial PRK); a diameter of 6.0 to 7.0 mm at a depth of 50 mm was ablated. The remaining thin epithelial layer was removed using a hard spear-shaped sponge. Following epithelial removal, the Wavelight Allegretto 200Hz excimer laser (Alcon Laboratories, Inc.) was used for stromal ablation. The excimer ablation zone was 9.0 mm for myopic astigmatism and 8.5 mm for myopic nonastigmatic treatment. The treatment zone comprised an optical zone of 6.0 to 7.0 mm and a transition zone of 1.5 to 3.0 mm. After excimer ablation, a sponge soaked with MMC 0.02% was placed on the stroma for 20 to 30, 30 to 40, 50 to 60, or 60 to 70 seconds (!4.0, 4.0 to 6.0, 6.0 to 8.0, or O8.0 diopters [D] of SE, respectively). The MMC was rinsed from the ocular surface and a contact lens placed on the cornea. Postoperatively, patients received a topical antibiotic, dexamethasone 0.1%, and artificial tears. They were examined at 1 day; 1 week; 1, 3, and 6 months; and as necessary. Patients were encouraged to return for examination if vision deteriorated at any time after surgery. Retreatment surgery was offered free of charge. The same nomogram was used for initial retreatments and regular treatments. Statistical Analysis Data were analyzed with Minitab software (version 17, Minitab, Inc.). For analysis of continuous data, the Student t test was used for normally distributed variables and Kruskal-Wallis test for nonparametric variables. For analysis of categorical variables, the chi-square test was used; when applicable, odds ratios (ORs) were calculated. Multivariate binary logistic regression analysis of all retreated eyes, adjusted for year of surgery by including year of surgery as a variable in the analysis, was performed to identify predictors of retreatment. For this purpose, all independent variables that had a P value less than 0.15 in the univariate analysis were included. Variables with high collinearity (correlation) were excluded from the multivariate analysis. The level of collinearity was assessed by the variance inflation factors of all candidate variables for the multivariate analysis. Variance inflation factors measure how much the Volume 43 Issue 6 June 2017

variance of the estimated regression coefficients are inflated compared with when the predictor variables are not linearly related. A variance inflation factor for a single explanatory variable is obtained using the r-squared value of the regression of that variable against all other explanatory variables; the higher the variance inflation factor, the higher the collinearity. Variables with a variance inflation factor more than 5 were considered to have excessive collinearity and were excluded from the multivariate model. Finally, variables of interest were stratified and categorically graphed as retreatment rates; the retreatment rate of each subgroup was compared with the overall retreatment rate using the chi-square test, and Bonferroni correction was applied for these multiple comparisons to avoid a type I error. Bonferronicorrected P values were adjusted so any value less than 0.05 was considered significant. Therefore, for all graphs, a P value less than 0.05 was considered significant. The rationale for this categorical analysis was to look for categorical cutoffs (subgroups) that were associated with increased and decreased retreatment rates. Logarithm of minimum angle of resolution (logMAR) visual acuities were used for all statistical calculations. These were then converted and reported in decimal/Snellen notation. A 2-sided P value less than 0.05 was considered statistically significant. All presented means are accompanied by their respective standard deviations. Since the variance between eyes is usually less than that between subjects, the overall variance of a sample of measurements combined from both eyes is likely to underestimate the true variance. Therefore, as in other studies,5 only right eyes were included in this study.

RESULTS A total of 9699 right eyes of 9699 consecutive patients were included in the final analysis. In patients who had bilateral surgery, the retreatment rate between right eyes and left eyes was similar, 2.3% and 2.2%, respectively (P Z .63). The mean age of the patients was 25.9 years G 7.3 (SD); 5243 (54.1%) were men. The mean preoperative subjective SE and astigmatism were 4.30 G 2.18 D (range 0.5 to 13.0 D; median 4.0 D) and 0.77 G 0.83 D (range 0 to 6.0 D; median 0.5 D), respectively. Two hundred twentythree eyes (2.30%) were retreated. Of those, 217 (2.24%) had a single retreatment and 6 (0.06%) had 2 retreatments. For each study year, a 2-year postoperative retreatment rate was calculated (Figure 1). During the study period, the 2-year retreatment rate decreased from 42 (6.17%) for primary PRK treatments done in 2005 to 2 (0.10%) for PRK treatments done in 2012 (R2 Z 0.79, P ! .001). The mean time between initial treatment and retreatment was 30.6 G 23.8 months (range 4 to 96 months; median 96 months), and more than half the retreatments were within 2 years (Figure 2). One hundred ninety-five (87.4%) of the first retreatments were myopic, 14 (6.3%) were hyperopic and 14 (6.3) were for mixed astigmatism. Sixteen eyes (7.4%) lost 1 or more lines of CDVA after a single retreatment. Table 1 shows the results of the univariate analysis comparing demographic and preoperative and intraoperative parameters in the retreatment and control groups. The retreatment group was older, more likely to have had transepithelial PRK, less likely to have had a large optical zone ablation (7.0 mm), and less likely to have an axis that was with the rule; it had better preoperative UDVA and CDVA, more preoperative subjective astigmatism and less

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Figure 1. A significant decrease in the 2-year retreatment rate was seen until 2008; thereafter, the retreatment rate was consistently low. The bold line is the actual 2-year retreatment rate. The thinner line is the exponential fit with the equation and relevant statistics.

preoperative subjective sphere, lower maximum ablation depth, and longer MMC exposure. The operating room humidity and temperature were higher and lower, respectively, in the retreatment group. No significant betweengroup differences were seen in SE, K power, and CCT. Table 2 shows the effect of preoperative and intraoperative factors on the odds of retreatment, based on multiple logistic regression analysis. The following parameters significantly influenced the odds of retreatment: More recent primary PRK treatment lowered the odds of retreatment (OR, 0.70); transepithelial PRK increased the odds of retreatment (OR, 5.12); and higher preoperative subjective astigmatism (OR, 1.74) increased the odds of retreatment. Age, preoperative CDVA, preoperative subjective SE, astigmatism axis, minimum K power, CCT, optical zone of 7.0 mm, MMC exposure time, and operating room humidity and temperature did not significantly affect the odds of retreatment in the multivariate analysis. Sphere and maximum ablation depth showed excessive collinearity with SE and were excluded from the multivariate analysis. Surgeons who performed more than 500 PRK surgeries were categorized as high-volume surgeons, and those who performed fewer than 200 PRK surgeries were pooled as low-volume surgeons. The Pearson chi-square test showed

a significant difference (P ! .001) in the retreatment rates of the 5 high-volume surgeons (range 2/608 [0.33%] to 128/4533 [2.82%]) and the 11 low-volume surgeons (30/345 [8.70%]). These 6 variables (5 high-volume and pooled low-volume surgeon rates) were entered into the multivariate model; 1 high-volume surgeon had a significantly lower retreatment rate on multivariate analysis (Table 2). Figure 3 shows that older age was associated with significantly higher retreatment rates, as seen in the 40 to 49 (n Z 492) and older than 50 (n Z 94) subgroups. Figure 4 shows that preoperative subjective sphere was not associated with a significantly higher or lower retreatment rate in any subgroup. Without Bonferroni correction, the 7.0 to 7.9 D subgroup had a significantly lower retreatment rate (n Z 565, P Z .04). Figure 5 shows that the retreatment rate was significantly higher in the subgroup with preoperative subjective astigmatism equal to or higher than 3.5 D and statistically significantly lower in the less than 1.5 D subgroup. Figure 6 shows that the subgroup with a maximum ablation depth of 30 to 45 mm was associated with significantly higher retreatment rates. The subgroups with a maximum ablation depth of less than 30 mm and of more than 135 mm had fewer eyes (n Z 286 and 117, respectively)

Figure 2. The time between primary treatment and retreatment using an expanded time scale for the first year.

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Table 1. Preoperative and intraoperative parameters. Retreatment Group (n Z 223)

Control Group (n Z 9476)

Odds Ratio

95% CI

Sex (% male)

57.9

54.0

1.17

0.89-1.53

.25

Astigmatism O 1.5 D (%)

21.5

12.8

1.87

1.35-2.58

!.001

Parameter

P Value

Transepithelial technique (%)

85.2

34.5

10.94

7.54-15.87

!.001

Optical zone (%) 6.0 mm 6.5 mm 7.0 mm

10.7 82.8 6.5

12.8 72.9 14.3

0.79 1.50 0.41

0.51-1.22 1.08-2.09 0.24-0.70

.28 .02 .001

Astigmatism axis (%) WTR Oblique ATR

36.4 46.4 17.2

44.1 40.8 15.1

0.67 1.44 1.11

0.51-0.89 0.88-1.50 0.77-1.59

.005 .32 .59

Age (y) G SD

27.2 G 9.0

25.9 G 7.2

d

d

.03

UDVA (logMAR)

1.3 G 0.5

1.5 G 0.6

d

d

.001

CDVA (logMAR)

0.02 G 0.06

0.0 G 0.05

d

d

!.001

Spherical equivalent (D)

4.06 G 2.35

4.30 G 2.18

d

d

.13

Sphere (D)

3.54 G 2.41

3.92 G 2.18

d

d

.02

Astigmatism (D)

1.04 G 1.13

0.77 G 0.82

d

d

!.001

Mean keratometric power (D)

43.88 G 4.52

44.15 G 1.82

d

d

.53

Minimum keratometric power (D)

43.34 G 1.97

43.66 G 1.57

d

d

.12 .18

Maximum keratometric power (D)

44.93 G 1.84

44.66 G 1.61

d

d

Central corneal thickness (mm)

521.5 G 38.2

526.4 G 37.1

d

d

.11

Maximum ablation depth (mm)

67.0 G 31.4

72.3 G 34.1

d

d

.01 !.001

Mitomycin-C application (seconds)

54 G 21.7

42 G 19.7

d

d

Humidity (%)

37.8 G 1.3

37.5 G 1.5

d

d

.005

Operating room temperature (Celsius)

22.5 G 1.3

23.2 G 1.2

d

d

.001

ATR Z against the rule; CDVA Z corrected distance visual acuity; CI Z confidence interval; UDVA Z uncorrected distance visual acuity; WTR Z with the rule Categorical variables are presented as percentages with appropriate odds ratio and continuous variables as mean G SD

than the 30 to 45 mm subgroup (n Z 1431) and therefore did not have statistically different retreatment rates. Moderate ablation depths were not associated with high retreatment rates. Without Bonferroni correction, the less than 30 mm and the 30 to 45 mm subgroups were associated with significantly higher retreatment rates (P Z .02 and P Z .002, respectively) and the 106 to 120 mm subgroup was associated with a significantly lower retreatment rate (P Z .04). Figure 7 shows that increased MMC exposure time was related to increased retreatment rates. Exposure subgroups

of 41 to 60 seconds (n Z 3087) and more than 60 seconds (n Z 633) were associated with significantly higher retreatment rates. DISCUSSION This retrospective database analysis of the preoperative and intraoperative parameters associated with retreatment after myopic PRK showed that high preoperative subjective astigmatism (R3.5 D), transepithelial PRK, and initial treatment before 2008 significantly increased the odds of

Table 2. Logistic regression analysis of preoperative and intraoperative factors predicting retreatment. Chi-Square

Odds Ratio

95% CI

P Value

14.00

0.70

0.58-0.84

!.001

Age (y)

0.31

1.01

0.98-1.04

.58

CDVA (logMAR)

0.27

3.44

0.03-362

.60

Subjective spherical equivalent (D)

1.67

0.92

0.80-1.05

.20

25.97

1.74

1.42-2.13

!.001

WTR axis

0.18

0.91

0.58-1.42

.67

Minimum keratometric power (D)

0.00

1.00

0.87-1.15

.98

Central corneal thickness (mm)

1.84

1.00

1.00-1.01

.18

Parameter Year of primary surgery

Subjective astigmatism (D)

32.39

5.12

2.90-9.05

!.001

Optical zone 7.0 mm

0.00

1.02

0.40-2.57

.97

Mitomycin-C exposure time (seconds)

0.24

1.00

0.98-1.01

.63

11.13

NA*

NA*

.049

Transepithelial technique

Surgeon comparison Operating room humidity (%)

0.43

0.95

0.77-1.14

.51

Operating room temperature (Celsius)

0.37

0.98

0.74-1.17

.54

CDVA Z corrected distance visual acuity; CI Z confidence interval; WTR Z with the rule All parameters were continuous variables except transepithelial technique (compared with alcohol-assisted mechanical epithelial removal), WTR axis (compared with all non-WTR axes), optical zone 7.0 mm (compared with pooled optical zones 6.0 and 6.5 mm), and surgeon (high-volume surgeons compared with each other and with pooled low-volume surgeons) *Not applicable because this summarizes 5 comparisons (1 high-volume surgeon with 4 high-volume surgeons and with pooled low-volume surgeons)

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Figure 3. Retreatment rates stratified by age. The P values, with Bonferroni correction applied, reflect chi-square tests comparing the retreatment rate in each subgroup with the overall retreatment rate of 2.30%.

retreatment. These parameters were significant on univariate and multivariate analyses. Surgeon factor was of borderline significance. We found that older age was significantly associated with retreatment in the univariate but not in the multivariate analysis. In the subgroup analysis, age older than 40 years was associated with higher retreatment rates. Age older than 40 years has been reported as a significant corneal refractive surgery retreatment risk.6–8 Surgeons are careful not to overtreat myopic presbyopic patients, and therefore there is a smaller margin of error than when treating young myopic patients. A second explanation may be that patients older than 40 may develop nuclear sclerosis, which may cause a myopic shift. In our cohort, almost half the retreatments occurred more than 2 years after the initial surgery, so lenticule-induced myopic shift was certainly possible. Subjective preoperative astigmatism increased the risk for retreatment more than any other preoperative parameter (OR of 1.74 for each diopter of astigmatism; P ! .001). This corroborates the findings of earlier studies.2,9 Figure 5 shows a significant increase in retreatment rate with astigmatism equal to or higher than 3.5 D. Possible reasons for astigmatism increasing the odds of retreatment

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more than sphere are that nomograms are less forgiving of inaccuracies in astigmatism treatment; centration is more important for astigmatic ablations than for spherical ablations; and since epithelial migration has been shown to be slower with deeper astigmatic ablations,10 eyes with higher astigmatism may have less predictable reepithelialization. The mean sphere was lower in the retreatment group than in the control group, but neither sphere nor SE were significantly associated with retreatment on multivariate analysis. Similarly, Figure 4 shows that sphere was not associated with a significant retreatment rate in any subgroup. Although highly myopic eyes have been reported to regress more than eyes with low myopia,11 this does not necessarily translate into higher retreatment rates. In our study, the sphere was greater than 10.00 D in only 71 eyes and the SE was greater than 10.00 D in only 111 eyes. Since few eyes had more than 10.00 D, their statistical influence was minor. Figure 4 suggests that although not statistically significant, myopia between 4.0 D and 7.9 D tended to require less retreatment, presumably because these patients had more realistic expectations than patients with low myopia and less tendency for myopic regression than patients with high myopia. It appears that in the modern PRK era, PRK effectively treats sphere up to approximately 10.0 D, while high astigmatism treatments are not as predictable. This means that lower SEs with astigmatism equal to or higher than 3.5 D are at greater risk for retreatment than higher SEs with astigmatism less than 1.5 D. Our finding has been corroborated by others, who found no correlation between the degree of myopia and the retreatment rate,2,12 although the older literature prior to routine MMC use for PRK showed that higher myopia had poorer refractive surgery outcomes.1,8 Maximum ablation depth was excluded from the multivariate analysis because of high collinearity with SE, sphere, and MMC application time. Figure 6, similar to the sphere graph (Figure 4), shows that the low-ablation subgroups had significantly higher retreatment rates, the middlerange ablation subgroups had lower retreatment rates, and the high-ablation subgroups had no significant increase in retreatments. It appears that the low maximum ablation

Figure 4. Retreatment rates stratified by sphere. The P values, with Bonferroni correction applied, reflect chi-square tests comparing the retreatment rate in each subgroup with the overall retreatment rate of 2.30%.

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Figure 5. Retreatment rates stratified by astigmatism. The P values, with Bonferroni correction applied, reflect chi-square tests comparing the retreatment rate in each subgroup with the overall retreatment rate of 2.30%.

depth subgroups contained the same eyes as the low-sphere subgroups. Possible reasons for higher retreatment rates may be higher patient expectations and higher astigmatism. The retreatment group had statistically significantly better, although not clinically significant, preoperative UDVA. This association was not borne out by the additional analyses that we performed. This could be due to overlapping statistical effects of low UDVA and high astigmatism in the multivariate analysis. Second, UDVA may be relatively inaccurate because myopic patients can easily increase their UDVA by an eyelid pinhole effect. Third, the retrospective study design may limit the fidelity of this parameter because the examiners may have been less pedantic with UDVA examinations below 20/200. Preoperative CDVA was also significantly better in the retreatment group, although the multivariate analysis failed to show a significant contribution to retreatment

rates. Categorical analysis of CDVA showed that in eyes with a CDVA worse than 20/20 (between 20/25 and 20/20), 149 (1.80%) of 8262 were retreated (OR, 0.34, 95% CI, 0.25-0.45) and in eyes with a CDVA better than 20/20, 74 (5.19%) of 1427 were retreated (OR, 2.98, 95% CI, 2.24-3.96) (chi-square comparison, P ! .001). This association of better preoperative CDVA with higher retreatment rates is consistent with the association of low sphere and low ablation depths with higher retreatment rates. We speculate that the common denominator was high patient expectation. Although our data cannot prove this hypothesis, it appears prudent to emphasize the importance of realistic patient expectation, careful patient selection, and effective preoperative counseling. The significant difference between retreatment rates in the high-volume and low-volume surgeons (2.52% versus 8.70%, P ! .001) may be explained by surgical decisions such as treatment zone and nomogram selection and by surgeon-patient interactions such as patient selection, management of patient expectation, and threshold for retreatment. The current study was not designed to differentiate between these possible causes of retreatment. The epithelial removal technique significantly influenced the retreatment rate. Transepithelial PRK had an OR for retreatment of 5.12 (P ! .001). This corroborates our recent study that showed that the long-term refractive outcomes were best for alcohol-assisted epithelial removal.13 In that study, we suggested that transepithelial PRK ablations may be less accurate because of significant variability in epithelial thickness between individuals.13 In contrast, others found that refractive outcomes in transepithelial PRK were comparable to those in alcohol-assisted mechanical epithelial removal.14 Recently developed high-resolution anterior segment spectral-domain optical coherence tomography has been shown to reliably assess epithelial thickness.15 The use of this technique to assess preoperative epithelial thickness may improve the outcomes of transepithelial PRK.

Figure 6. Retreatment rates stratified by maximum ablation depth. The P values, with Bonferroni correction applied, reflect chi-square tests comparing the retreatment rate in each subgroup with the overall retreatment rate of 2.30%.

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In conclusion, the modern PRK era has seen a significant decrease in myopic PRK retreatment rates. It appears that alcohol-assisted epithelial removal is preferred to transepithelial PRK. Paying special attention to eyes with preoperative subjective astigmatism equal to or higher than 3.5 D may further decrease the need for myopic PRK retreatment.

WHAT WAS KNOWN

Figure 7. Retreatment rates stratified by MMC exposure times. The P values, with Bonferroni correction applied, reflect chi-square tests comparing the retreatment rate in each subgroup with the overall retreatment rate of 2.30%.

 Astigmatism increases the risk for retreatment after myopic PRK.  Controversy exists regarding the best technique of epithelial removal for PRK.  Retreatment rates after myopic corneal laser surgery are declining.

WHAT THIS PAPER ADDS

The larger optical zone of 7.0 mm decreased the odds of retreatment in the univariate analysis but not in the multivariate analysis (OR, 1.02). Mitomycin-C exposure time was related to retreatment rate in the univariate analysis but not in the multivariate analysis (OR, 1.00). This suggests that optical zone size and MMC exposure time are not associated with PRK retreatment rate. Lower operating room temperature was associated with significantly more retreatments in the univariate analysis but not in the multivariate analysis. Although the manufacturer of the Allegretto excimer laser recommends room temperatures above 20 C, we are not aware of published clinical data reporting that PRK is less precise at room temperatures lower than 20 C. This issue may warrant further study, specifically for PRK because little has been published on the effect of room temperature. Studies of LASIK have not shown a significant association between room temperature and refractive surgery outcomes.16,17 Our study has limitations. The retrospective study design did not allow us to assess differing patient (and surgeon) tolerances to ametropia. The number of postPRK ametropic patients who did not return for retreatment was not known, even though this service was encouraged. There are no data about the compliance of patients with the recommended postoperative steroid eyedrop protocol. Because only myopic PRK individuals were included, the conclusions cannot be applied to those with hyperopia or mixed astigmatism. Future study of these groups is warranted. The primary surgeries were performed over 7 years. During this period, surgeons improved their techniques, fine-tuned their nomograms, and incorporated new technologies such as software updates for the eye tracker. Potential areas of future research are the influence of the timing of retreatment (which had a large SD of 23.8 months), a comparative study of the refractive outcomes of eyes having and not having retreatment, multiple retreatment outcomes, and a comparative study of the outcomes of the various surgical techniques used for retreatment.

 In the modern PRK era, retreatment rates have continued to decline.  Transepithelial PRK increased the odds of retreatment.  Preoperative low myopia and CDVA better than 20/20 tended to increase retreatment rates.

REFERENCES 1. 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 2. Randleman JB, White AJ Jr, Lynn MJ, Hu MH, Stulting RD. Incidence, outcomes, and risk factors for retreatment after wavefront-optimized ablations with PRK and LASIK. J Refract Surg 2009; 25:273–276 3. Hersh PS, Fry KL, Bishop DS. Incidence and associations of retreatment after LASIK. Ophthalmology 2003; 110:748–754. Available at: http://www.visioninstitute.com/new-jersey/pdfs/lasik_retreatment.pdf. Accessed April 6, 2017 4. Gwiazda J, Grice K, Held R, McLellan J, Thorn F. Astigmatism and the development of myopia in children. Vision Res 2000; 40:1019–1026. Available at: http://www.sciencedirect.com/science/article/pii/S0042698999002370. Accessed April 6, 2017 5. Armstrong RA. Statistical guidelines for the analysis of data obtained from one or both eyes. Ophthalmic Physiol Opt 2013; 33:7–14. Available at: http://onlinelibrary.wiley.com/doi/10.1111/opo.12009/pdf. Accessed April 6, 2017 6. Hersh PS, Schein OD, Steinert R, Summit Photorefractive Keratectomy Phase III Study Group. Characteristics influencing outcomes of excimer laser photorefractive keratectomy. Ophthalmology 1996; 103:1962–1969. Available at: http://www.vision-institute.com/new-jersey/pdfs/characteristics_ influencing_outcomes_of_excimer_laser_prk.pdf. Accessed April 6, 2017 7. Rao SN, Chuck RS, Chang AH, LaBree L, McDonnell PJ. Effect of age on the refractive outcome of myopic photorefractive keratectomy. J Cataract Refract Surg 2000; 26:543–546 8. Ditzen K, Handzel A, Pieger S. Laser in situ keratomileusis nomogram development. J Refract Surg 1999; 15:S197–S201 9. Shortt AJ, Allan BDS, Evans JR. Laser-assisted in-situ keratomileusis (LASIK) versus photorefractive keratectomy (PRK) for myopia. Cochrane Database Syst Rev 2013; 31:CD005135. Summary available at: http://onlinelibrary. wiley.com/doi/10.1002/14651858.CD005135.pub3/abstract. Accessed April 6, 2017 10. Serrao S, Lombardo M. Corneal epithelial healing after photorefractive keratectomy: analytical study. J Cataract Refract Surg 2005; 31:930–937 ~a-Garcia P. Fifteen years follow-up of 11. Alio JL, Soria FA, Abbouda A, Pen photorefractive keratectomy up to 10 D of myopia: outcomes and analysis of the refractive regression. Br J Ophthalmol 2016; 100:626–632 12. Shortt AJ, Allan BDS. Photorefractive keratectomy (PRK) versus laserassisted in-situ keratomileusis (LASIK) for myopia. Cochrane Database Syst Rev 2006; 19:CD005135 13. Shapira Y, Mimouni M, Levartovsky S, Varssano D, Sela T, Munzer G, Kaiserman I. Comparison of three epithelial removal techniques in PRK: Mechanical, alcohol-assisted, and transepithelial laser. J Refract Surg 2015; 31:760–766

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14. Luger MHA, Ewering T, Arba-Mosquera S. Consecutive myopia correction with transepithelial versus alcohol-assisted photorefractive keratectomy in contralateral eyes: one-year results. J Cataract Refract Surg 2012; 38:1414–1423 15. Urs R, Lloyd HO, Reinstein DZ, Silverman RH. Comparison of very-highfrequency ultrasound and spectral-domain optical coherence tomography corneal and epithelial thickness maps. J Cataract Refract Surg 2016; 42:95–101 16. Urbano de Souza IR, Peltier de Queiroz Urbano de Souza A, Peltier de  N. InfluQueiroz Urbano de Souza A, Figueiredo P, Jesus RS, Kara-Jose ence of temperature and humidity on laser in situ keratomileusis outcomes. J Refract Surg 2001; 17:S202–S204 17. Seider MI, McLeod SD, Porco TC, Schallhorn SC. The effect of procedure room temperature and humidity on LASIK outcomes. Ophthalmology 2013; 120:2204–2208. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3779502/pdf/nihms-470341.pdf. Accessed April 6, 2017

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Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned.

First author: Russell Pokroy, MD Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel