August 2016
Volume 57, Issue 10
Open Access
Glaucoma  |   August 2016
Effect of Glaucoma Surgery on the Progression Rate and Pattern in Glaucoma Patients With Myopia
Author Affiliations & Notes
  • Hae-Young Lopilly Park
    Department of Ophthalmology and Visual Science Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
  • Rowoon Yi
    Department of Ophthalmology and Visual Science Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
  • Younhea Jung
    Department of Ophthalmology and Visual Science Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
  • Chan Kee Park
    Department of Ophthalmology and Visual Science Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
  • Correspondence: Chan Kee Park, Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea; ckpark@catholic.ac.kr
Investigative Ophthalmology & Visual Science August 2016, Vol.57, 4170-4179. doi:10.1167/iovs.16-19564
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      Hae-Young Lopilly Park, Rowoon Yi, Younhea Jung, Chan Kee Park; Effect of Glaucoma Surgery on the Progression Rate and Pattern in Glaucoma Patients With Myopia. Invest. Ophthalmol. Vis. Sci. 2016;57(10):4170-4179. doi: 10.1167/iovs.16-19564.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To evaluate the effect of myopia on the changes of visual field (VF) and retinal nerve fiber layer (RNFL) thickness after glaucoma surgery.

Methods: Patients with primary open-angle glaucoma who underwent glaucoma surgery due to uncontrolled IOP, with at least four VF and optical coherence tomography (OCT) examinations before and after surgery (total of eight VF and OCT examinations), and follow-ups of at least 4 years, were enrolled and classified according to axial length. Disc ovality ratio, degree of disc torsion, and ratio between peripapillary atrophy area and disc area were measured from disc photographs. The rate of change of the VF parameters and RNFL thickness was determined by using a linear regression analysis and compared according to the degree of myopia.

Results: A total of 63 eyes with myopia and 46 eyes without myopia were analyzed. The rate of change in the sensitivity of the central VF (within 10° region) and temporal RNFL thickness differed significantly between the myopic and nonmyopic groups (P < 0.01 and P < 0.01, respectively). Axial length (P < 0.01), magnitude of IOP change after surgery (P < 0.01), the presence of postoperative hypertensive phase (P < 0.01), and peripapillary atrophy to disc area ratio (P < 0.01) were significantly related to the change of the central VF and temporal RNFL thickness.

Conclusions: Myopic eyes with large peripapillary atrophy relative to the disc area seem to show greater central VF progression and temporal RNFL thinning after glaucoma surgery when they are exposed to large IOP change of glaucoma surgery.

Myopia, especially high myopia, is a well-known risk factor for glaucoma development.13 A recent meta-analysis4 reveals a pooled odds ratio of 2.46 for high myopia and 1.77 for low myopia, with a cutoff value of −3.0 diopters (D), from 11 population-based studies. The role of myopia in glaucoma progression, however, is controversial. Many studies propose that myopia, especially high myopia, is a risk factor for glaucoma progression.58 In the Advanced Glaucoma Intervention Study (AGIS), myopic eyes with more than −4.0 D tended to progress faster.9 Other studies, however, report that myopia does not contribute to the progression of glaucoma and most of the studies examined eyes with normal-tension glaucoma (NTG).1012 A systematic review of 85 articles reveals that an association between myopia and glaucoma progression is only found in primary open-angle glaucoma (POAG), which is unlikely in eyes with NTG.13 It seems that the level of intraocular pressure (IOP) may affect the role of myopia in glaucoma progression, yet this requires further elucidation. Eyes with elevated or uncontrolled IOP that undergo glaucoma surgery are exposed to high IOP, and analyzing the characteristics of these patients with myopia may provide insight into the role of IOP in the association between myopia and glaucoma progression. 
In the present study, we evaluated glaucoma progression after glaucoma surgery and analyzed the role of myopia in the changes of the visual field (VF) and retinal nerve fiber layer (RNFL) thickness. 
Methods
Subjects
We retrospectively reviewed the medical records of 772 POAG patients who underwent glaucoma surgery due to uncontrolled IOP (presenting with IOP > 22 mm Hg on at least 3 separate days during preoperative follow-up), performed by one surgeon (CKP) at the glaucoma clinic of Seoul St. Mary's Hospital between 2008 and 2011. From this cohort, we enrolled those eyes that underwent successful reduction of IOP after glaucoma surgery, had a minimum of four preoperative and four postoperative reliable Swedish interactive threshold algorithm standard 24-2 fields (Swedish interactive threshold algorithm standard automated perimetry, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc., Dublin, CA, USA) and optical coherence tomography (OCT) examinations, and were followed up for a minimum of 2 years before and after surgery. Glaucoma surgery was indicated whenever there was suspected glaucoma progression or the IOP was considered uncontrolled for the extent of glaucomatous damage. Successful IOP reduction after surgery was defined as all follow-up IOP measurements less than 21 mm Hg (with or without topical hypotensive medications) without any additional operating room surgical interventions. The Institutional Review Board from Seoul St. Mary's Hospital approved this study, which adhered to the principles of the Declaration of Helsinki. 
Each medical record was reviewed to collect patient demographics and methods of surgical intervention. Baseline examinations included best-corrected visual acuity (BCVA), refraction, slit-lamp biomicroscopy, gonioscopy, central corneal thickness using ultrasound pachymetry (Tomey Corporation, Nagoya, Japan), axial length using ocular biometry (IOL Master; Carl Zeiss Meditec), dilated stereoscopic examination of the optic disc, disc and red-free fundus photography (Canon, Tokyo, Japan), Heidelberg retina tomography (HRT; Heidelberg Engineering GmbH, Heidelberg, Germany), Cirrus OCT (Carl Zeiss Meditec), and Humphrey VF examination. Preoperative and postoperative IOP measurements using Goldmann applanation tonometry at every visit were recorded for calculation of mean IOP. Change of IOP was the difference between preoperative IOP at admission for surgery and IOP at postoperative day 1. Early postoperative IOP was the mean of IOP at postoperative day 1, day 3, and week 1. Cataract grading was performed by the same ophthalmologist using the lens opacities classification system III (LOCS III) grading system during preoperative and postoperative follow-up.14 
The presence of postoperative complication was recorded, such as hypotony (defined as IOP < 6 mm Hg during postoperative 1-month period), shallow anterior chamber, choroidal detachment, and presence of hypertensive phase (defined as IOP > 21 mm Hg during the first postoperative 3-month period). Patients with decreased BCVA underwent macular OCT and fundus examinations to observe any postoperative complications. 
For glaucoma diagnosis, patients had to fulfill the following criteria: glaucomatous optic disc changes (such as diffuse or localized rim thinning, a notch in the rim, or a vertical cup-to-disc ratio greater than that of the other eye by more than 0.2) and glaucomatous VF loss (defined as a pattern standard deviation [P < 0.05] or glaucoma hemifield test results [P < 0.01] outside the normal limits in a consistent pattern on two qualifying VFs), both confirmed by two glaucoma specialists (H-YLP, CKP); and an open angle on gonioscopic examination. 
All patients had to meet the following additional inclusion criteria at baseline: age more than 18 years, BCVA ≥ 20/40, and mean deviation (MD) better than −12.00 dB. Patients were excluded on the basis of any of the following criteria: a progression of cataract defined as increase in LOCS grading by more than 1 scale or who needed cataract surgery postoperatively; any postoperative complication that required further intervention; eyes that needed a second procedure or surgery; history of any retinal disease, including diabetic or hypertensive retinopathy; history of eye trauma or surgery with the exception of uncomplicated cataract surgery; other optic nerve diseases besides glaucoma; and history of systemic or neurologic diseases that might affect the VF. If both eyes met the inclusion criteria, one eye was randomly chosen for the study. 
Patients were classified into four groups according to the axial length. Eyes with axial length shorter than 24.0 mm, from 24.0 to 26.0 mm, from 26.0 to 30.0 mm, or longer than 30.0 mm were classified into nonmyopic, mild myopic, high myopic, and extreme myopic groups, respectively. 
Measurement of Optic Disc Tilt, Torsion, and Peripapillary Atrophy (PPA) to Disc Area
Digital retinal photographs centered on the optic disc and macular region were obtained by using standardized settings. Parameters were measured from photographs by two observers (H-YLP, YJ) using ImageJ 1.40 software (http://rsb.info.nih.gov/ij/index.html; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA). Disc tilt was identified by the disc ovality ratio, defined as the ratio between the longest diameter (LD) and shortest diameter (SD) of the optic disc (tilt ratio = LD/SD).1517 Torsion was identified and defined as the deviation of the long axis of the optic disc from the vertical meridian.18,19 The vertical meridian was considered to be a vertical line 90° from a horizontal line connecting the fovea—which was 2° to 6° below the optic disc—to the center of the optic disc. The angle between the vertical meridian and the LD of the optic disc was considered the degree of torsion. The β-zone PPA (an inner crescent of chorioretinal atrophy with visible sclera and choroidal vessels) and the clinical disc margin were plotted by using a mouse-driven cursor to trace the disc and PPA margins directly onto the image. Then the pixel areas of the β-zone PPA and clinical disc were obtained with the ImageJ software. The ratio of PPA pixel area to the disc pixel area was calculated from the measurements. Details have been described previously (Fig. 1).20 
Figure 1
 
Identification of the disc ovality ratio, torsion degree, and peripapillary area to disc area ratio by ImageJ software. Left: Disc ovality ratio was defined as the ratio between the longest diameter (LD) and shortest diameter (SD) of the optic disc. Middle: Torsion degree (θ) was measured between the LD and the vertical meridian (red line) 90° away from the horizontal line (red line) connecting the fovea and the center of the optic disc. Right: peripapillary atrophy area and disc area were manually outlined (white line) and the pixel area was automatically calculated with the software. The peripapillary atrophy was identified as the β-zone peripapillary atrophy adjacent to the optic disc and is characterized by atrophy of the retinal pigment epithelium and choriocapillaris, thinning of chorioretinal tissues, and visible sclera and choroidal vessels.
Figure 1
 
Identification of the disc ovality ratio, torsion degree, and peripapillary area to disc area ratio by ImageJ software. Left: Disc ovality ratio was defined as the ratio between the longest diameter (LD) and shortest diameter (SD) of the optic disc. Middle: Torsion degree (θ) was measured between the LD and the vertical meridian (red line) 90° away from the horizontal line (red line) connecting the fovea and the center of the optic disc. Right: peripapillary atrophy area and disc area were manually outlined (white line) and the pixel area was automatically calculated with the software. The peripapillary atrophy was identified as the β-zone peripapillary atrophy adjacent to the optic disc and is characterized by atrophy of the retinal pigment epithelium and choriocapillaris, thinning of chorioretinal tissues, and visible sclera and choroidal vessels.
Analysis of the Change in the Visual Field
Visual field testing was performed with optical correction by using either trial lenses or disposable hydrophilic contact lenses in eyes with myopia. Only reliable VF tests results (less than 20% fixation losses, 15% false-positive responses, and 15% false-negative responses) were included in the analysis. The same criteria were used to determine reliability for baseline VF tests before and after surgery. Visual field progression was determined by linear regression analysis of MD and pattern standard deviation (PSD) values. The MD and PSD progression rate was expressed as a change in decibels per year. We also examined the total deviation (TD) in the central or peripheral regions. The central region was defined as the sum of the 12 central points within 10° of the VF. The peripheral region was the sum of the remaining 40 points, which was modified from our previous report.21 The foveal region was defined as the sum of the four innermost central points within 6° of the VF. The VF change in each region was determined by linear regression analysis of mean threshold of each designated zone. 
The slopes for VF changes were calculated as mean slope during the total follow-up period, that is, preoperative, operative, and postoperative slopes. Preoperative slope was calculated from the preoperative data. Postoperative slope was calculated from the postoperative data. Operative slope was calculated from two preoperative and two postoperative data analyses that were performed closest to the operative day. The slopes for each measurement between groups were compared by using an independent t-test or 1-way ANOVA with post hoc multiple comparisons. 
Additionally, the AGIS score was analyzed to determine progression.22 The AGIS score is based on the analysis of the total deviation map of the VF 24-2 test. The score for each VF ranges from 0 (no defect) to 20 (end-stage). The mean change from baseline in VF defect score was calculated in each group. 
Analysis of the Change of RNFL Thickness by OCT
The RNFL thickness was measured by using the Optic Disc Cube protocol of a Cirrus OCT running version 6.0 software. The Optic Disc Cube protocol scans a 6 × 6-mm2 area centered on the optic nerve head and collects 200 × 200 axial scans containing 40,000 points. A calculation circle, 3.46 mm in diameter consisting of 256 A-scans, was automatically positioned around the optic disc. Retinal nerve fiber layer thickness was determined at 256 points at a set diameter around the center of the optic disc, and the mean values were used to yield 12 clock-hour thicknesses, four quadrant thicknesses, and global average RNFL thickness measurements. Pupil dilatation was performed if necessary. All accepted images exhibited a centered optic disc or fovea; were well focused, with even and adequate illumination; had no eye motions within the measurement circle; and had a signal strength ≥ 7. 
A linear mixed model against time was performed for the global average and the individual clock-hour and quadrant thicknesses in each subject. The slope of the regression equation represented the rate of change in the RNFL thickness. The slopes for each measurement were compared between the groups by using an independent t-test or 1-way ANOVA with post hoc multiple comparisons. 
Statistical Analysis
To evaluate the interobserver reproducibility of measuring parameters of disc morphology and PPA to disc area ratio, 30 randomly selected eyes were evaluated and the intraclass correlation coefficient (ICC) was calculated. According to Fleiss,23 ICC scores of ≥0.75, 0.40–0.75, and ≤0.4 are considered to be excellent, moderate, and poor, respectively. 
An independent t-test or 1-way ANOVA with post hoc multiple comparisons was used to compare differences between groups. Comparison between preoperative and postoperative values was performed by using paired t-test. Linear regression analysis was used to evaluate the influence of several factors, such as preoperative and postoperative follow-up periods, age, axial length, central corneal thickness, baseline treated IOP, maximum uncontrolled IOP, early and final postoperative IOP, baseline MD, baseline average RNFL thickness, disc ovality ratio, degree of disc torsion, and PPA to disc area ratio. P values less than 0.05 were considered statistically significant. Variables with a significance of P < 0.10 were included in the multivariate regression analysis. Statistical analysis was performed by using the SPSS statistical package (SPSS, Chicago, IL, USA). 
Results
A total of 63 eyes with myopia and 46 eyes without myopia that met the inclusion criteria were analyzed. Baseline characteristics, except for age, spherical equivalent, and axial length, were similar between groups, as shown in Table 1. The subgroups of myopic eyes showed no difference in the baseline characteristics except for spherical equivalent and axial length. The baseline central sensitivity of the VF was similar between groups. The type of glaucoma surgery was similar between groups. The mean preoperative and postoperative follow-up periods were similar between groups, as shown in Table 2. The number of VFs and OCTs that were included in the analysis were similar between groups. 
Table 1
 
Baseline Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 1
 
Baseline Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 2
 
Follow-up Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 2
 
Follow-up Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Measurement of disc ovality ratio, disc torsion, and PPA to disc area ratio by the two observers showed excellent reproducibility (ICC of 0.97 for ovality ratio, 0.98 for disc torsion, and 0.97 for PPA to disc area ratio). The disc ovality ratio, disc torsion, and PPA to disc area ratio were significantly different between the nonmyopic and myopic groups (Table 3). Between the subgroups of myopic eyes, only PPA to disc area ratio differed significantly among the mild, high, and extreme myopic groups. 
Table 3
 
Characteristic of the Optic Disc Morphology of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 3
 
Characteristic of the Optic Disc Morphology of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Comparisons of the preoperative and postoperative slopes of the VF parameters between the groups did not show significant difference. However, there were significant differences in operative slope of VF parameters, as shown in Table 4. There were significant differences in terms of VF change in MD and PSD between the myopic (−4.7 ± 3.2 dB/y for MD, −1.5 ± 1.4 dB/y for PSD) and the nonmyopic (−2.3 ± 2.1 dB/y for MD, −0.9 ± 2.0 dB/y for PSD) groups. When the comparison was made according to location, the change in the sensitivity of the peripheral VF region from the TD plot did not differ between the myopic and nonmyopic groups (P = 0.38). The change in the sensitivity of the central VF region and the foveal sensitivity from the TD plot, however, differed significantly between the myopic and nonmyopic groups (P < 0.01 and P < 0.01, respectively). A comparison between the subgroups of myopic eyes revealed a significant difference in the VF change of MD (P < 0.01). When the comparison was made according to the location, the change in the sensitivity of the peripheral VF region from the TD plot did not differ between subgroups of myopic eyes (P = 0.30). The change in the sensitivity of the central VF region from the TD plot, however, differed significantly between the extreme myopic group and the mild and high myopic groups (P < 0.01). The change of AGIS score was significantly different between the myopic and nonmyopic groups (P < 0.01), and between subgroups of myopia. 
Table 4
 
Comparison of the Operative Slope/Change in the Advanced Glaucoma Intervention Study Score of the Visual Field Parameters Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 4
 
Comparison of the Operative Slope/Change in the Advanced Glaucoma Intervention Study Score of the Visual Field Parameters Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Comparisons of the operative slope of the RNFL thickness parameters between the groups are shown in Table 5. The rate of change in the inferior and temporal RNFL thickness differed significantly between myopic and nonmyopic groups (P = 0.09 and P < 0.01, respectively). Comparison between subgroups of myopic eyes showed significant differences in average and temporal RNFL thickness, with greater thinning in the extreme myopic group (P < 0.01 and P < 0.01, respectively). By clock-hour analysis, the rate of change in RNFL thickness differed significantly between nonmyopic and myopic eyes at the 6- and 7-o'clock positions in the inferior quadrant and at 8-, 9-, and 10-o'clock positions in the temporal quadrant (Fig. 2). 
Table 5
 
Comparison of Operative Slope of the Retinal Nerve Fiber Layer Thicknesses Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 5
 
Comparison of Operative Slope of the Retinal Nerve Fiber Layer Thicknesses Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Figure 2
 
Comparison of the rate of change of the VF and RNFL thickness measured by optical coherence tomography between preoperative and postoperative slopes in myopic and nonmyopic eyes that underwent glaucoma surgery. Top left: The change in the MD of the VF (dB/y) differed significantly between preoperative and postoperative slopes in high and extreme myopia. Top right: The change in preoperative and postoperative slopes of the sensitivity of the central 10° of the visual field differed significantly in myopic eyes. The change in sensitivity also differed significantly between subgroups of myopic eyes. Bottom left: The change in the average RNFL thickness (μm/y) differed significantly between preoperative and postoperative slopes in extreme myopic eyes. Bottom right: The rate of temporal RNFL thinning (μm/y) differed between preoperative and postoperative slopes in myopic eyes, and there was significant difference between subgroups of myopic eyes. Asterisks indicate significant difference between groups by paired t-test.
Figure 2
 
Comparison of the rate of change of the VF and RNFL thickness measured by optical coherence tomography between preoperative and postoperative slopes in myopic and nonmyopic eyes that underwent glaucoma surgery. Top left: The change in the MD of the VF (dB/y) differed significantly between preoperative and postoperative slopes in high and extreme myopia. Top right: The change in preoperative and postoperative slopes of the sensitivity of the central 10° of the visual field differed significantly in myopic eyes. The change in sensitivity also differed significantly between subgroups of myopic eyes. Bottom left: The change in the average RNFL thickness (μm/y) differed significantly between preoperative and postoperative slopes in extreme myopic eyes. Bottom right: The rate of temporal RNFL thinning (μm/y) differed between preoperative and postoperative slopes in myopic eyes, and there was significant difference between subgroups of myopic eyes. Asterisks indicate significant difference between groups by paired t-test.
To determine the factors related to the rate of change in the central VF, a linear regression analysis, with the dependent variable being the change in the sensitivity of the central VF region from the TD plot, was performed (Table 6). Age (P = 0.02), axial length (P = 0.01), change of IOP (P = 0.02), presence of postoperative hypertensive phase (P = 0.07), degree of disc torsion (P = 0.02), and PPA to disc area ratio (P < 0.01) were significantly related factors in univariate analysis. Axial length (P < 0.01), change of IOP (P < 0.01), presence of hypertensive phase (P < 0.01), and PPA to disc area ratio (P < 0.01) were also significantly related factors in multivariate analysis. 
Table 6
 
Related Factors to the Rate of Visual Field Sensitivity Change in the Central Region (Within 10° of the Visual Field) in Glaucomatous Eyes That Underwent Glaucoma Surgery
Table 6
 
Related Factors to the Rate of Visual Field Sensitivity Change in the Central Region (Within 10° of the Visual Field) in Glaucomatous Eyes That Underwent Glaucoma Surgery
To determine the factors related to the rate of change in the temporal RNFL thickness, a linear regression analysis, with the dependent variable being the change in the temporal RNFL thickness, was performed (Table 7). Age (P = 0.03), axial length (P < 0.01), change of IOP (P < 0.01), presence of postoperative hypertensive phase (P = 0.07), and PPA to disc area ratio (P < 0.01) were significantly related factors in univariate analysis. Axial length (P < 0.01), change of IOP (P < 0.01), presence of postoperative hypertensive phase (P < 0.01), and PPA to disc area ratio (P < 0.01) were also significantly related factors in multivariate analysis. 
Table 7
 
Related Factors to the Rate of Temporal Retinal Nerve Fiber Layer Thinning Measured by Optical Coherence Tomography in Glaucomatous Eyes That Underwent Glaucoma Surgery
Table 7
 
Related Factors to the Rate of Temporal Retinal Nerve Fiber Layer Thinning Measured by Optical Coherence Tomography in Glaucomatous Eyes That Underwent Glaucoma Surgery
In subgroup analysis, we divided patients according to the presence of postoperative complication including hypotony, shallow anterior chamber, and choroidal detachment. Nine of 46 (19.6%) in the nonmyopic group and 8 of 63 (12.7%) had postoperative hypotony-related complications. Comparison of the postoperative complication rate, such as hypotony, shallow anterior chamber, and choroidal detachment, did not differ between nonmyopic and myopic group and between subgroups of myopia. Comparison of postoperative BCVA, slopes of VF, and OCT parameters between myopic and nonmyopic eyes with postoperative hypotony-related complications showed no significant difference (data not shown). However, the presence of postoperative hypertensive phase was significantly more frequent in the myopic group (n = 20, 31.7%) than in the nonmyopic group (n = 6, 13.0%; P = 0.02). The presence of postoperative hypertensive phase was also significantly different between the mild myopic (n = 3, 15.0%), high myopic (n = 6, 27.3%), and extreme myopic groups (n = 11, 52.4%; P = 0.03). Comparison between myopic and nonmyopic eyes with postoperative hypertensive phase exhibited significant difference in terms of the slope of the MD (−2.7 ± 1.2 dB/y for nonmyopic and −5.4 ± 2.8 dB/y for myopic eyes; P < 0.01), central sensitivity of the VF (−2.5 ± 1.7 dB/y for nonmyopic and −6.2 ± 3.1 dB/y for myopic eyes; P < 0.01), and temporal RNFL thickness (−1.2 ± 1.4 dB/y for nonmyopic and −2.7 ± 2.2 dB/y for myopic eyes; P < 0.01). 
Discussion
We observed that eyes with myopia that underwent glaucoma surgery showed more rapid VF and OCT progression than eyes without myopia. Especially, operative progression, defined as changes between preoperative and postoperative VF and OCT parameters near the operation time point, significantly showed greater progression in myopic eyes. Glaucoma progression was pronounced in the central region of the VF and temporal and inferior region, based on OCT in myopic eyes that underwent glaucoma surgery. Factors related to central VF progression and temporal RNFL thinning were axial length, the magnitude of the change in IOP before and immediately after surgery, presence of hypertensive phase, and PPA to disc area ratio. Myopic eyes that experienced fluctuation of IOP, which was the change in IOP or presence of postoperative hypertensive phase, had pronounced glaucoma progression in terms of VF and RNFL changes, especially extreme myopia, with an axial length > 30.0 mm, which was related to the PPA to disc area ratio. Finally, the pattern of progression differed between myopic eyes and nonmyopic eyes that underwent glaucoma surgery. 
The main differences between myopic and nonmyopic eyes were the morphology of the optic disc and the β-zone PPA. In particular, eyes with extreme myopia had a significantly larger PPA to disc area ratio than eyes with mild and high myopia. The PPA to disc area ratio was one factor related to VF and OCT progression other than myopia itself in multivariate analysis. The β-zone PPA is adjacent to the optic disc and is characterized by atrophy of the retinal pigment epithelium and choriocapillaris, thinning of the chorioretinal tissues, and visible sclera and choroidal vessels.24 Eyes with glaucoma have a larger β-zone PPA than normal controls and this correlates with the severity of glaucoma.25,26 Recently, β-zone PPA was found to be related to glaucoma development in ocular hypertensive eyes and to faster glaucoma progression in eyes with established glaucoma.27,28 Also, glaucomatous eyes with a β-zone PPA are at increased risk of progressive RNFL thinning, based on OCT.29 The exact mechanism underlying the relationship between β-zone PPA and glaucoma needs to be elucidated. In one study, however, showing that the location of the β-zone PPA predicts the region of the most rapid VF progression, the authors30 have hypothesized that ischemic optic nerve damage could be the underlying mechanism. They mention that the vasculature in the PPA region may be obliterated or closed by increased IOP. The prelaminar portion of the optic nerve head receives its blood supply from the peripapillary choroid from branches of the short posterior ciliary arteries; therefore, closure of the choriocapillaris in the PPA region could damage the axons of the retinal ganglion cells.31 The β-zone PPA is usually larger in eyes with myopia and gets larger with increasing myopia.32,33 If ischemia of the PPA region induced by high IOP contributes to glaucoma, myopic eyes with a large PPA region may be more susceptible to glaucoma progression than nonmyopic eyes after exposure to high IOP, which is the finding of the present study. This may explain, in part, why myopia is a prognostic factor for POAG, but not for NTG, based on a meta-analysis study.13 
Intraocular pressure fluctuation is an important factor related to glaucoma progression.34,35 One more possible explanation for the fast progression in myopic eyes compared to nonmyopic eyes after exposure to high IOP or fluctuation of IOP during surgery/after surgery may be related to the biomechanical properties of myopic eyes. Axial length has been shown to be a significant predictor of biomechanical properties measured by ocular response analyzer.36,37 Longer axial length has been associated with lower corneal hysteresis in Chinese school children, which may represent more compliant and deformable optic nerve head structures.37 When exposed to similar degree of high IOP or fluctuation of IOP, myopic eyes may tend to experience greater deformity of the optic nerve head, which could contribute to more damage in the retinal ganglion cells during surgery or in the early postoperative period. Caution is needed in myopic eyes to minimize IOP fluctuation during surgery and to reduce the frequency of postoperative hypertensive phase after surgery, especially high myopic eyes with greater risk for developing postoperative hypertensive phase after glaucoma drainage device.38 Recently, the use of early aqueous suppressant on glaucoma drainage device has reduced the frequency of hypertensive phase and this may be considered when operating myopic eyes.39 
The progression pattern in myopic eyes after glaucoma surgery differed from that in nonmyopic eyes. In general, glaucoma progression is observed mainly at the inferotemporal and superotemporal region of the optic disc and the arcuate region of the VF, preserving the central 10°.40,41 The temporal region of the optic disc or central VF is retained until the end-stage of the disease.42 Myopic eyes, however, showed the fastest progression at the inferior and temporal quadrants, and the difference in RNFL thickness was prominent at the 9-o'clock position as compared to nonmyopic eyes. Central VF progression has recently been reported to be associated with underlying vascular component of glaucoma in a subset of patients.21,4345 Temporal and inferior RNFL thinning is usually a distinct pattern in eyes with ischemic or genetic optic neuropathies.4648 Both VF and RNFL changes may suggest an underlying ischemic mechanism from elevated IOP or IOP fluctuation in myopic eyes that underwent glaucoma surgery. The PPA to disc area ratio was commonly related to the changes in the VF and RNFL, suggesting that a large PPA relative to the disc and elevated IOP or IOP fluctuation may have contributed to this distinct progression pattern in myopic glaucomatous eyes during glaucoma surgery or at early postoperative period. These have important clinical implications. The progression pattern of myopic eyes involves the central VF and temporal RNFL, including the papillomacular bundle, which might result in early visual acuity reduction and impaired quality of life. In eyes with myopia, high IOP or IOP fluctuation should be carefully monitored. Representative cases are shown in Figure 3. After glaucoma surgery, early central VF progression (Fig. 3, top) and temporal RNFL thinning (Fig. 3, top, bottom) occurred in myopic eyes with large PPA. 
Figure 3
 
Representative cases showing the pattern of progression in glaucomatous eyes with myopia that underwent glaucoma surgery due to uncontrolled IOP. A 28-year-old male with uncontrolled IOP who had trabeculectomy in his left eye. Axial length was 27.47 mm, indicating high myopia. Compared to the VF and RNFL thickness by OCT in 2011, progression is noted in the central region of the VF and temporal RNFL of the OCT maps after surgery at 2012. There is not much change thereafter during postoperative follow-ups as shown in the bottom graphs.
Figure 3
 
Representative cases showing the pattern of progression in glaucomatous eyes with myopia that underwent glaucoma surgery due to uncontrolled IOP. A 28-year-old male with uncontrolled IOP who had trabeculectomy in his left eye. Axial length was 27.47 mm, indicating high myopia. Compared to the VF and RNFL thickness by OCT in 2011, progression is noted in the central region of the VF and temporal RNFL of the OCT maps after surgery at 2012. There is not much change thereafter during postoperative follow-ups as shown in the bottom graphs.
Our study had several limitations. It was a retrospective design with a relatively small sample size and short follow-up period. There may be several factors that affect central VF progression. Although not different between groups, baseline differences in the central sensitivity, even if minimal for detection, should be accounted for. The type of surgery that was performed, or macular changes after postoperative periods due to hypotony, can also affect the central VF region and should be considered. Change in PPA over time was not assessed, nor was a change in medications or surgical therapy during follow-up. We did not measure the PPA size in absolute units. We did not correct the magnification factor in myopic patients in term of the measured PPA area and RNFL thickness. Because the disc area is also affected by a magnification factor, the ratio between the PPA area and disc area was used. For RNFL thickness, we measured the rate of change, which may be less affected by a magnification factor when the measurement of RNFL thickness is used for diagnostic purposes. Our findings should be interpreted with caution, as both uncontrolled IOP and surgery may have affected glaucoma progression. 
In conclusion, we found that change in IOP and presence of postoperative hypertensive phase after glaucoma surgery affected eyes with myopia, which progressed faster than eyes without myopia. The pattern of progression in myopic eyes differed from that in nonmyopic eyes and was pronounced in the central region of the VF and temporal RNFL in myopic eyes. Myopic eyes with large PPA area relative to the disc area seem to show greater central VF progression and temporal RNFL thinning after glaucoma surgery when they are exposed to IOP fluctuation. Glaucoma surgery in glaucomatous eyes with myopia should be cautiously considered in various ways to minimize IOP fluctuation during and after operation. 
Acknowledgments
Supported by the National Research Foundation of Korea Grant funded by the Korean government (MSIP) (No. NRF-2014R1A1A3049403). 
Disclosure: H.-Y.L. Park, None; R. Yi, None; Y. Jung, None; C.K. Park, None 
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Figure 1
 
Identification of the disc ovality ratio, torsion degree, and peripapillary area to disc area ratio by ImageJ software. Left: Disc ovality ratio was defined as the ratio between the longest diameter (LD) and shortest diameter (SD) of the optic disc. Middle: Torsion degree (θ) was measured between the LD and the vertical meridian (red line) 90° away from the horizontal line (red line) connecting the fovea and the center of the optic disc. Right: peripapillary atrophy area and disc area were manually outlined (white line) and the pixel area was automatically calculated with the software. The peripapillary atrophy was identified as the β-zone peripapillary atrophy adjacent to the optic disc and is characterized by atrophy of the retinal pigment epithelium and choriocapillaris, thinning of chorioretinal tissues, and visible sclera and choroidal vessels.
Figure 1
 
Identification of the disc ovality ratio, torsion degree, and peripapillary area to disc area ratio by ImageJ software. Left: Disc ovality ratio was defined as the ratio between the longest diameter (LD) and shortest diameter (SD) of the optic disc. Middle: Torsion degree (θ) was measured between the LD and the vertical meridian (red line) 90° away from the horizontal line (red line) connecting the fovea and the center of the optic disc. Right: peripapillary atrophy area and disc area were manually outlined (white line) and the pixel area was automatically calculated with the software. The peripapillary atrophy was identified as the β-zone peripapillary atrophy adjacent to the optic disc and is characterized by atrophy of the retinal pigment epithelium and choriocapillaris, thinning of chorioretinal tissues, and visible sclera and choroidal vessels.
Figure 2
 
Comparison of the rate of change of the VF and RNFL thickness measured by optical coherence tomography between preoperative and postoperative slopes in myopic and nonmyopic eyes that underwent glaucoma surgery. Top left: The change in the MD of the VF (dB/y) differed significantly between preoperative and postoperative slopes in high and extreme myopia. Top right: The change in preoperative and postoperative slopes of the sensitivity of the central 10° of the visual field differed significantly in myopic eyes. The change in sensitivity also differed significantly between subgroups of myopic eyes. Bottom left: The change in the average RNFL thickness (μm/y) differed significantly between preoperative and postoperative slopes in extreme myopic eyes. Bottom right: The rate of temporal RNFL thinning (μm/y) differed between preoperative and postoperative slopes in myopic eyes, and there was significant difference between subgroups of myopic eyes. Asterisks indicate significant difference between groups by paired t-test.
Figure 2
 
Comparison of the rate of change of the VF and RNFL thickness measured by optical coherence tomography between preoperative and postoperative slopes in myopic and nonmyopic eyes that underwent glaucoma surgery. Top left: The change in the MD of the VF (dB/y) differed significantly between preoperative and postoperative slopes in high and extreme myopia. Top right: The change in preoperative and postoperative slopes of the sensitivity of the central 10° of the visual field differed significantly in myopic eyes. The change in sensitivity also differed significantly between subgroups of myopic eyes. Bottom left: The change in the average RNFL thickness (μm/y) differed significantly between preoperative and postoperative slopes in extreme myopic eyes. Bottom right: The rate of temporal RNFL thinning (μm/y) differed between preoperative and postoperative slopes in myopic eyes, and there was significant difference between subgroups of myopic eyes. Asterisks indicate significant difference between groups by paired t-test.
Figure 3
 
Representative cases showing the pattern of progression in glaucomatous eyes with myopia that underwent glaucoma surgery due to uncontrolled IOP. A 28-year-old male with uncontrolled IOP who had trabeculectomy in his left eye. Axial length was 27.47 mm, indicating high myopia. Compared to the VF and RNFL thickness by OCT in 2011, progression is noted in the central region of the VF and temporal RNFL of the OCT maps after surgery at 2012. There is not much change thereafter during postoperative follow-ups as shown in the bottom graphs.
Figure 3
 
Representative cases showing the pattern of progression in glaucomatous eyes with myopia that underwent glaucoma surgery due to uncontrolled IOP. A 28-year-old male with uncontrolled IOP who had trabeculectomy in his left eye. Axial length was 27.47 mm, indicating high myopia. Compared to the VF and RNFL thickness by OCT in 2011, progression is noted in the central region of the VF and temporal RNFL of the OCT maps after surgery at 2012. There is not much change thereafter during postoperative follow-ups as shown in the bottom graphs.
Table 1
 
Baseline Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 1
 
Baseline Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 2
 
Follow-up Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 2
 
Follow-up Characteristics of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 3
 
Characteristic of the Optic Disc Morphology of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 3
 
Characteristic of the Optic Disc Morphology of Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 4
 
Comparison of the Operative Slope/Change in the Advanced Glaucoma Intervention Study Score of the Visual Field Parameters Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 4
 
Comparison of the Operative Slope/Change in the Advanced Glaucoma Intervention Study Score of the Visual Field Parameters Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 5
 
Comparison of Operative Slope of the Retinal Nerve Fiber Layer Thicknesses Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 5
 
Comparison of Operative Slope of the Retinal Nerve Fiber Layer Thicknesses Between Myopic and Nonmyopic Glaucoma Patients Who Underwent Glaucoma Surgery
Table 6
 
Related Factors to the Rate of Visual Field Sensitivity Change in the Central Region (Within 10° of the Visual Field) in Glaucomatous Eyes That Underwent Glaucoma Surgery
Table 6
 
Related Factors to the Rate of Visual Field Sensitivity Change in the Central Region (Within 10° of the Visual Field) in Glaucomatous Eyes That Underwent Glaucoma Surgery
Table 7
 
Related Factors to the Rate of Temporal Retinal Nerve Fiber Layer Thinning Measured by Optical Coherence Tomography in Glaucomatous Eyes That Underwent Glaucoma Surgery
Table 7
 
Related Factors to the Rate of Temporal Retinal Nerve Fiber Layer Thinning Measured by Optical Coherence Tomography in Glaucomatous Eyes That Underwent Glaucoma Surgery
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