Journal of Refractive Surgery

Original Article Supplemental Data

Comparison of Corneal Epithelial Remodeling After Femtosecond Laser–Assisted LASIK and Small Incision Lenticule Extraction (SMILE)

Ik-Hee Ryu, MD; Bong Jun Kim, MD; Jong-Hyuck Lee, MD, PhD; Sun Woong Kim, MD, PhD

Abstract

PURPOSE:

To comparatively investigate changes in epithelial thickness between myopic femtosecond laser–assisted LASIK (FS-LASIK) and small incision lenticule extraction (SMILE).

METHODS:

This study compared the topographic epithelial thickness changes in 175 myopic eyes undergoing FS-LASIK (62 eyes) or SMILE (113 eyes). Epithelial thickness was obtained using spectral-domain optical coherence tomography before surgery and 1 and 3 months after surgery. Topographic epithelial thickness obtained by automatic algorithm and thickness variability (standard deviation over 17 imaged areas) was compared between two groups. Postoperative epithelial thickness changes were correlated with treatment parameters.

RESULTS:

For FS-LASIK, the mean epithelial thickness of the center zone (2 mm in diameter), paracenter (2 to 5 mm), and mid-periphery (5 to 6 mm) increased by 3.4, 4.3, and 2.1 µm, respectively, at 1 month and by 4.4, 5.1, and 2.9 µm, respectively, at 3 months. There was an increase of 2.5, 3.9, and 4.5 µm, respectively, at 1 month and 3.0, 4.2, and 4.9 µm, respectively, at 3 months following SMILE. The epithelial thickness did not change between 1 and 3 months postoperatively following SMILE, whereas it increased further after FS-LASIK. A larger increase of epithelial thickness was observed in the central zone at 3 months following FS-LASIK than SMILE, whereas the opposite was observed in the mid-periphery. The topographic thickness variability was greater after FS-LASIK than SMILE. Corneal epithelial thickening was proportional to the amount of myopia correction after both procedures.

CONCLUSIONS:

Topographic epithelial remodeling patterns differ following FS-LASIK or SMILE. Epithelial remodeling appears to stabilize more rapidly following SMILE than FS-LASIK.

[J Refract Surg. 2017;33(4):250–256.]

Abstract

PURPOSE:

To comparatively investigate changes in epithelial thickness between myopic femtosecond laser–assisted LASIK (FS-LASIK) and small incision lenticule extraction (SMILE).

METHODS:

This study compared the topographic epithelial thickness changes in 175 myopic eyes undergoing FS-LASIK (62 eyes) or SMILE (113 eyes). Epithelial thickness was obtained using spectral-domain optical coherence tomography before surgery and 1 and 3 months after surgery. Topographic epithelial thickness obtained by automatic algorithm and thickness variability (standard deviation over 17 imaged areas) was compared between two groups. Postoperative epithelial thickness changes were correlated with treatment parameters.

RESULTS:

For FS-LASIK, the mean epithelial thickness of the center zone (2 mm in diameter), paracenter (2 to 5 mm), and mid-periphery (5 to 6 mm) increased by 3.4, 4.3, and 2.1 µm, respectively, at 1 month and by 4.4, 5.1, and 2.9 µm, respectively, at 3 months. There was an increase of 2.5, 3.9, and 4.5 µm, respectively, at 1 month and 3.0, 4.2, and 4.9 µm, respectively, at 3 months following SMILE. The epithelial thickness did not change between 1 and 3 months postoperatively following SMILE, whereas it increased further after FS-LASIK. A larger increase of epithelial thickness was observed in the central zone at 3 months following FS-LASIK than SMILE, whereas the opposite was observed in the mid-periphery. The topographic thickness variability was greater after FS-LASIK than SMILE. Corneal epithelial thickening was proportional to the amount of myopia correction after both procedures.

CONCLUSIONS:

Topographic epithelial remodeling patterns differ following FS-LASIK or SMILE. Epithelial remodeling appears to stabilize more rapidly following SMILE than FS-LASIK.

[J Refract Surg. 2017;33(4):250–256.]

Femtosecond lasers have become available for refractive surgery in the past decade. They are extremely precise and are increasingly being used to create flaps for LASIK.1,2 Small incision lenticule extraction (SMILE) was recently introduced; this removes the refractive lenticule through an incision of 2 to 5 mm in length without the need for flap creation.3 The use of SMILE preserves most of the anterior stroma and epithelium and so it is expected to result in less disruption to the corneal biomechanics than LASIK.4–6 The visual outcomes and safety of SMILE have been reported to be comparable to LASIK.7–9

The recent availability of corneal epithelial imaging by anterior segment optical coherence tomography (AS-OCT) provides a practical tool for in vivo epithelial mapping, which demonstrates good repeatability in both normal and post-LASIK eyes.10–14 It allows for measurement of corneal epithelial thickness in the clinical routine with adequate speed and resolution in a non-contact way.13 Numerous studies have reported an increase in epithelial thickness following LASIK,15–23 but only a few studies have examined epithelial thickness changes after SMILE6,24,25; moreover, there have been no studies comparing epithelial remodeling patterns following the two procedures. The mechanisms underlying these postoperative epithelial changes are not fully understood, but epithelial hyperplasia is known to contribute to postoperative regression.15,16,22 A better understanding of epithelial remodeling might help surgeons predict the epithelial response to refractive surgery, thereby improving the predictability of these procedures. This study compared epithelial thickness changes after myopic femtosecond laser–assisted LASIK (FS-LASIK) and SMILE using AS-OCT.

Patients and Methods

Patients

This prospective observational study included 175 eyes that had undergone uneventful FS-LASIK (62 eyes) or SMILE (113 eyes) at the B & VIIT Eye Center (Seoul, Korea) between October 2015 and January 2016. All surgeries were performed by the same experienced surgeon (I-HR). A complete ophthalmic examination was performed to screen for corneal abnormalities and determine patient eligibility for refractive surgery. The inclusion criteria were: age 20 to 45 years, stable myopia for at least 1 year, corrected distance visual acuity of 20/25 or better, spherical equivalent refraction of −2.00 to −7.00 diopters (D), and refractive astigmatism of less than 3.00 D. The exclusion criteria were as follows: the use of hard contact lenses, a central corneal thickness of less than 480 µm, a calculated postoperative residual stromal bed of less than 250 µm, and the presence of other ocular pathologic conditions such as corneal dystrophy, keratoconus, corneal opacity, or a history of previous ocular surgery. The study protocol was approved by the institutional review board and was conducted according to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients.

FS-LASIK Procedure

The corneal flap was created with the VisuMax FS laser system (Carl Zeiss Meditec AG, Jena, Germany) using a pulse of 140 nJ and a repetition rate of 500 kHz. The intended diameter and flap thickness were 8 mm and 120 µm, respectively. The position and angle of the hinge were set at the 12-o'clock position and 90°, respectively. The track and spot distances were set as 3 mm for flap creation and 1.5 mm for making the flap side cut, respectively. After lifting the flap, the Amaris 1050RS excimer laser system (Schwind eye-techsolutions, GmbH, Kleinostheim, Germany) was used to perform stromal ablation, after which the flap was carefully repositioned over the stroma.

SMILE Procedure

SMILE was performed using a VisuMax 500-kHz femtosecond laser. A 2-mm incision was made at the 145° meridian and the upper and lower edges of the lenticule were delineated so that the tissue planes were well defined. The upper interface was separated and the lower layer was dissected. Once both layers had been separated, the lenticule was removed from the cornea. The diameter of the cap was 7.5 mm and the optical zone diameter was between 6.3 and 6.6 mm. The intended cap thickness was 120 µm.

Measurement of Corneal Epithelial and Stromal Thickness

The corneal epithelial and total thickness data were obtained preoperatively and 1 and 3 months postoperatively using the RTVue anterior segment OCT (AS-OCT) system (Optovue, Inc., Fremont, CA) with a corneal adaptor module set at a wavelength of 830 nm. We scanned the cornea in eight meridians using a “Pachymetry + Cpwr” scan (software version A6.11.0.12) over a 6-mm diameter centered at the corneal vertex. The epithelial thickness maps were generated using an automatic algorithm and were divided into a total of 17 sectors: a central 2-mm diameter zone, eight paracentral zones within an annulus between the 2- and 5-mm diameter rings, and eight mid-peripheral zones within an annulus between the 5- and 6-mm diameter rings.11–14 We generated stromal thickness maps by subtracting the epithelial thickness from the corneal thickness, as described previously.26 The mean values in the 17 areas were calculated, as were the mean values in the eight paracentral zones and eight mid-peripheral zones; the topographic thickness variability (the standard deviation over the entire imaged area) was also determined. The thickness values for the left eyes were shown on the vertical axis and superimposed onto the right eye values so that the nasal/temporal characteristics could be combined. The same investigator conducted all OCT imaging. Two consecutive acquisitions were obtained to ensure the validity of the data and the average value was used for analysis.

Statistical Analysis

Statistical analyses were performed using SPSS for Windows (version 21.0; IBM Corp., Armonk, NY). In each group, epithelial thickness and stromal thickness were compared using the repeated measures analysis of variance with Bonferroni correction. The difference in the thickness between the two groups was compared using the Student's t test. Simple linear regression analyses were performed to investigate the influence of preoperative spherical equivalent, ablation depth, and preoperative epithelial thickness on changes in epithelial thickness following surgery. A P value of less than .05 was considered significant.

Results

The study consisted of 175 eyes of 37 male and 51 female patients undergoing FS-LASIK (62 eyes) or SMILE (113 eyes) for myopia correction. The mean age, sex ratio, preoperative spherical equivalent refractive power, and optical zone diameter were matched between the two groups. There was a significant difference between planned maximum (central) lenticule thickness for SMILE and ablation depth for FS-LASIK even though target myopia correction and planned optical zone diameter were matched between the two groups (Table 1). The mean postoperative refractive error at 1 and 3 months was −0.19 ± 0.48 and −0.26 ± 0.49 D after SMILE and 0.16 ± 0.49 and 0.06 ± 0.41 D after FS-LASIK, respectively. All eyes had a postoperative CDVA of 20/20, with 100 of 113 eyes (88.5%) after SMILE and 56 of 62 (90.3%) eyes after FS-LASIK within ±0.50 D of the intended correction.


Demographic Characteristics

Table 1:

Demographic Characteristics

Epithelial Thickness Changes

Preoperative epithelial thickness in the 17 segments was similar in the two groups. At both 1 and 3 months postoperatively, epithelial thickness showed a statistically significant increase in the center, paracenter, and mid-peripheral regions in both groups. A further increase in the central zone at 3 months compared to 1 month postoperatively was observed after FS-LASIK (Figure 1). In the central zone, epithelial thickness increased more after FS-LASIK than after SMILE at both 1 and 3 months postoperatively (Table 2). In contrast, epithelial thickness showed a greater increase after SMILE than after FS-LASIK in the mid-periphery for both postoperative measurements (P < .001). Topographic epithelial thickness variability was greater after FS-LASIK than SMILE for both postoperative measurements (P < .001).


Corneal epithelium thickness and topographic thickness variability increased postoperatively following both small incision lenticule extraction (SMILE) and femtosecond laser–assisted LASIK (FS-LASIK). Progressive epithelial thickening was observed between 1 and 3 months postoperatively after FS-LASIK, but not after SMILE (repeated measures analysis of variance with Bonferroni correction). Topographic thickness variability was greater after FS-LASIK than SMILE.

Figure 1.

Corneal epithelium thickness and topographic thickness variability increased postoperatively following both small incision lenticule extraction (SMILE) and femtosecond laser–assisted LASIK (FS-LASIK). Progressive epithelial thickening was observed between 1 and 3 months postoperatively after FS-LASIK, but not after SMILE (repeated measures analysis of variance with Bonferroni correction). Topographic thickness variability was greater after FS-LASIK than SMILE.


Comparison of the Change in Postoperative Corneal Epithelial Thickness

Table 2:

Comparison of the Change in Postoperative Corneal Epithelial Thickness

Stromal (Non-Epithelial) Thickness Changes

When compared to preoperative values, there was a larger decrease in the postoperative stromal thickness in the center than in the mid-periphery. Although there was no difference in corrected spherical equivalent power between the two groups, stromal thickness change was significantly greater after SMILE than FS-LASIK (Table A, available in the online version of this article). For SMILE, the actual stromal change at the center observed with AS-OCT was 10.1 and 11.9 µm lower than the programmed maximal lenticule thickness at 1 and 3 months postoperatively. In contrast, there was no significant difference between the observed and planned stromal thickness change after FS-LASIK. Figure A (available in the online version of this article) shows the results of linear regression analysis comparing stromal change measured using RTVue with the planned ablation depth/lenticule thickness.


Comparison of the Change in Postoperative Stromal Thickness

Table A:

Comparison of the Change in Postoperative Stromal Thickness


Scatter plot of achieved stromal thickness change versus planned ablation depth in femtosecond laser–assisted LASIK or lenticule thickness in small incision lenticule extraction. The red line represents equality between the measured stromal thickness change and the planned ablation depth or lenticule thickness. Points above the red line signify that the achieved stromal thickness change is less than the planned ablation depth.

Figure A.

Scatter plot of achieved stromal thickness change versus planned ablation depth in femtosecond laser–assisted LASIK or lenticule thickness in small incision lenticule extraction. The red line represents equality between the measured stromal thickness change and the planned ablation depth or lenticule thickness. Points above the red line signify that the achieved stromal thickness change is less than the planned ablation depth.

Correlation Analysis

The changes in epithelial thickness showed a statistically significant linear association with the magnitude of preoperative refractive error and ablation depth (lenticule thickness for SMILE) in both groups. There was also an inverse correlation with preoperative epithelial thickness across all regions (Table 3). No correlation was observed between the change in epithelial thickness and the change in refractive error between 1 and 3 months postoperatively.


Correlation Between Change in Corneal Epithelial Thickness and Various Factors

Table 3:

Correlation Between Change in Corneal Epithelial Thickness and Various Factors

Discussion

It is widely recognized that the corneal epithelium, which is highly reactive to irregularities and changes in the underlying stromal shape, undergoes remodeling in response to corneal refractive surgery.20–28 A previous study using very high-frequency digital ultrasound reported that a lenticular shape change in the epithelial thickness profile occurred after LASIK, with more thickening occurring centrally than paracentrally.22 A slightly different pattern of epithelial thickening has been observed using AS-OCT.21,28 Kanellopolous and Asimellis21 described a negative meniscus-like lenticular pattern, with more significant thickening at the paracenter than at the center, in agreement with the results of the current study. We observed less thickening in the mid-periphery (5- to 6-mm radius), which is also consistent with previous findings.21,22 Tang et al. reported that maximum epithelial thickening was noted at an annular area 3 to 4 mm in diameter and tapered off toward the periphery.28 We suggest that variations in laser ablation profiles induce differences in epithelial remodeling. Further increases in central epithelial thickening between 1 and 3 months following LASIK have also been reported, but epithelial thickness stabilized after 3 months.22,23,28 Our results reconfirm previous findings that there is a linear relationship between epithelial thickening and the degree of myopic correction. The central epithelial thickness increased after SMILE to compensate for the stromal tissue that was removed; a similar response was observed after FS-LASIK, as previously described.6,24,25 It is interesting to note that the increase in central epithelial thickness was smaller in the SMILE group despite the removal of a larger amount of stromal tissue. Epithelial thickness changes were less marked centrally but increased radially (centrifugally) toward the mid-periphery after SMILE. Thus, compared with post-LASIK eyes, a greater increase in the epithelial thickness was observed in the mid-peripheral zone (5 to 6 mm) in the SMILE group. The postoperative changes in epithelial thickness are presumed to be related to biomechanical remodeling and a change in the underlying stromal curvature.21,28

The comparison of preoperative and postoperative stromal thickness reduction can provide a direct method for evaluating the predictability of refractive surgery. The degree of precision of pachymetry measurements is an essential factor in the utility of this assessment. Our results showed that the planned lenticule thickness was 11.9 µm thicker on average than the achieved stromal thickness change at 3 months postoperatively in the SMILE group, whereas ablation depth showed only a 0.4-µm mean difference with the stromal thickness change in the FS-LASIK group. Interestingly, the observed difference between stromal change and planned lenticule thickness or ablation depth could partly explain postoperative refractive results in both groups: −0.26 ± 0.49 D after SMILE and 0.06 ± 0.41 D after FS-LASIK.

Previous studies have demonstrated good repeatability for the RTVue AS-OCT system for the measurement of epithelial and corneal thickness in both post-LASIK and normal eyes (within-subject standard deviation [Sw]: 0.7 to 0.9).10–12 We assessed the intra-user repeatability in 36 eyes that had undergone SMILE 1 to 6 months previously by calculating Sw, the coefficient of variation, and the intraclass correlation coefficient for the three consecutive measurements, and found a good repeatability for epithelial thickness measurements (Sw in center: 0.8, Table B, available in the online version of this article). It should be noted that epithelial thickness measurement becomes increasingly challenging and less repeatable toward the corneal periphery. For this reason, epithelial thickness measurement in mid-periphery suffers from less repeatability (Sw in mid-periphery: 1.2 to 1.5, Table B).


Repeatability of Corneal Epithelial Thickness Measurement Using RTVue

Table B:

Repeatability of Corneal Epithelial Thickness Measurement Using RTVue

Because the same methodology was used to investigate the stromal thickness change in both groups, the scatter due to measurement error can be assumed to be identical. For most of the eyes in the SMILE group (111 of 113), the achieved stromal reduction was less than the planned tissue removal (Figure A). Therefore, any of the observed differences in SMILE are not likely to be a result of an error in postoperative RTVue measurements, but presumably represent a systemic difference. Interestingly, the observed difference between lenticule thickness and stromal thickness change is similar to a previous report (8.2 µm) using very high-frequency digital ultrasound.6 Based on their previous research showing high reproducibility of cap thickness in SMILE,30 the authors speculated that this difference was due to biomechanical changes in the stroma. They attributed the difference to central stromal expansion caused by the biomechanical changes occurring following SMILE. One possible mechanism could be that the lamellae severed by the lenticule between the residual bed and the cap might expand slightly, owing to a release of tension.6 This postoperative biomechanical stromal remodeling could partly explain the comparatively smaller amount of epithelial thickening observed in eyes after SMILE compared to after LASIK. The observed reduction in central epithelial hyperplasia in SMILE could be explained by the compensatory response to stromal expansion.

Another explanation is the difference in size of the treatment area. Previous studies demonstrated that epithelial hyperplasia after photorefractive keratectomy was greater with smaller optical zone sizes.29 As observed by other research groups,9 we confirmed that the diameter of the postoperative treatment zone is significantly larger in SMILE than in LASIK even though the planned optical zone size is matched. Thus, a larger optical zone and a significant change in curvature at the mid-periphery (5- to 6-mm annulus) could explain the smaller amounts of central epithelial thickening and increased epithelial thickening at the mid-periphery following SMILE. A smaller postoperative optical zone with a gradual transition zone could explain the greater amounts of central thickening and the smaller thickening at the mid-periphery in the LASIK group.

It is not clear why the mid-peripheral thickening is greater than the central changes following SMILE. If central stromal expansion occurs as presumed by a previous study,6 it could partly explain this apparently paradoxical finding. The topographic epithelial remodeling pattern of this study is different from a previous finding, which described a lenticular shape change in epithelial thickness following SMILE.25 The difference might be attributed to the specifics of instrumentation, difference in measurement area (only horizontal scan on 5 mm vs 8 radial scans on 6 mm), and method of analysis (a single point thickness vs averaged thickness value on defined zones). Further studies are required to confirm this finding and to investigate the nature of the biomechanical changes.

A possible limitation of this study is that the follow-up period of 3 months was not long enough to observe any refractive regression or to conclude that corneal epithelial remodeling had finished. Previous studies have reported that epithelial thickness stabilizes after 3 months following LASIK,22,23,28 but no studies have examined this following SMILE. The current study found no further epithelial thickening between 1 and 3 months after SMILE in mild to moderate myopia. Higher amounts of myopic correction in a different population could induce more thickening and further progression. It has been suggested that epithelial hyperplasia may be responsible for perceived regression, but we did not observe this in the current study, possibly due to the highly stabilized refractive results. Studies using long-term follow-up in individuals with a greater degree of myopia, and a consequent increased possibility of regression, may be warranted to investigate this association.

This study demonstrated that epithelial thickness increase was proportional to the amount of myopia correction and ablation depth after both SMILE and FS-LASIK. The degree of epithelial hyperplasia is greater in eyes after LASIK than after SMILE in both the central and paracentral regions. The topographical pattern of epithelial remodeling differs between the two procedures, and remodeling seems to stabilize faster in eyes after SMILE.

References

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Demographic Characteristics

CharacteristicFS-LASIK (n = 62)SMILE (n = 113)P
Male:female26:3647:66
Age (y)27.52 ± 6.33 (20 to 43)26.15 ± 5.53 (20 to 41).196
Mean SE (D)−4.23 ± 1.21 (−2.13 to −6.63)−4.23 ± 1.27 (−2.00 to −7.00).996
Optical zone (mm)6.41 ± 0.10 (6.3 to 6.7)6.39 ± 0.09 (6.3 to 6.6).139
Planned ablation depth (µm)68.29 ± 18.50 (37 to 111)89.23 ± 21.37 (51 to 127)< .001

Comparison of the Change in Postoperative Corneal Epithelial Thickness

ParameterFS-LASIK (n = 62)SMILE (n = 113)P
1 month postoperative
  Central (µm)3.44 ± 2.892.51 ± 2.36.024
  Paracentral (µm)4.34 ± 2.903.90 ± 2.28.264
  Midperipheral (µm)2.10 ± 2.754.49 ± 2.52< .001
3 months postoperative
  Central (µm)4.37 ± 2.752.97 ± 3.36.006
  Paracentral (µm)5.12 ± 2.484.22 ± 3.02.046
  Midperipheral (µm)2.87 ± 2.444.86 ± 2.68< .001

Correlation Between Change in Corneal Epithelial Thickness and Various Factors

ParameterFS-LASIK (n = 62)SMILE (n = 113)


R2βPR2βP
Lenticule thickness/ablation depth
  Central0.1010.340.0070.0500.241.010
  Paracentral0.1940.455< .0010.1370.381< .001
  Mid-periphery0.0240.201.1180.1060.338< .001
Spherical equivalent
  Central0.087−0.320.0110.097−0.325< .001
  Paracentral0.150−0.405.0010.188−0.442< .001
  Mid-periphery0.005−0.084.5170.106−0.337< .001
Preoperative epithelial thickness
  Central0.287−0.546< .0010.029−0.172.040
  Paracentral0.143−0.396< .0010.040−0.220.019
  Mid-periphery0.101−0.340.0070.148−0.395< .001

Comparison of the Change in Postoperative Stromal Thickness

ParameterFS-LASIK (n = 62)SMILE (n = 113)P
1 month postoperative
  Central (µm)−70.61 ± 21.50−79.14 ± 20.23.010
  Paracentral (µm)−50.40 ± 16.80−60.05 ± 15.15< .001
  Mid-peripheral (µm)−29.70 ± 15.45−39.78 ± 13.83< .001
3 months postoperative
  Central (µm)−68.63 ± 22.22−77.37 ± 20.03.009
  Paracentral (µm)−48.66 ± 17.20−58.38 ± 15.84< .001
  Mid-peripheral (µm)−29.34 ± 16.84−38.26 ± 14.04< .001

Repeatability of Corneal Epithelial Thickness Measurement Using RTVue

PatientsCenter (2 mm)Paracenter (2 to 5 mm)Midperiphery (5 to 6 mm)Source



SwCVICCSwCVICCSwCVICC
Post-SMILE0.81.440.9680.9 to 1.11.68 to 1.97≥0.9091.2 to 1.52.23 to 2.93≥0.866Current study
Post-LASIK0.71.050.9950.8 to 1.71.23 to 2.00≥0.9571.4 to 2.21.95 to 3.03≥0.891Ref 12
Normal0.71.070.9850.6 to 0.90.98 to 1.30≥0.9670.8 to 1.21.25 to 1.71≥0.917Ref 12
Normal0.7Ref 10
Normal0.88Ref 11
Authors

From B & VIIT Eye Center, Seoul, South Korea (I-HR); and the Department of Ophthalmology, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, South Korea (BJK, J-HL, SWK).

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

Drs. Ryu and B. J. Kim contributed equally to this work and should be considered as equal first authors.

AUTHOR CONTRIBUTIONS

Study concept and design (J-HL, SWK); data collection (IH-R, BJK); analysis and interpretation of data (IH-R, BJK, J-HL, SWK); writing the manuscript (IH-R, BJK, SWK); critical revision of the manuscript (J-HL, SWK); statistical expertise (IH-R, BJK, J-HL); administrative, technical, or material support (SWK); supervision (SWK)

Correspondence: Sun Woong Kim, MD, PhD, Department of Ophthalmology, Yonsei University Wonju College of Medicine, 20, Ilsan-ro, Wonju, Gangwon-do, 26426, South Korea. E-mail: eyedockim@yonsei.ac.kr

Received: June 22, 2016
Accepted: January 03, 2017

10.3928/1081597X-20170111-01

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