Subjects

This was a retrospective longitudinal study. Candidates of this study were patients with OAG in eyes both with and without myopia, who initially visited Samsung Medical Center (Seoul, South Korea) between January 2000 and December 2008. OAG eyes with more than 7 years of follow-up and that had been subjected to more than 9 VF tests were included. This study followed all guidelines for experimental investigation in human subjects, was approved by the Samsung Medical Center Institutional Review Board, and adhered to the tenets of the Declaration of Helsinki.

Participants underwent a comprehensive ophthalmic assessment, including slit-lamp biomicroscopy, Goldmann applanation tonometry, manifest refraction, gonioscopic examination, dilated stereoscopic examination of the ONH and color fundus photography, automated perimetry using the central 30-2 Humphrey Field Analyzer (HFA model 640 or model 740; Humphrey Instruments Inc, San Leandro, California, USA), axial length (AL) measurement (IOLMaster; Carl Zeiss Meditec Inc, Dublin, California, USA), and ultrasound pachymetry (Tomey SP-3000; Tomey Ltd, Nagoya, Japan). The extent of VF defect was measured using mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Reliable VF analysis was defined as a false-negative rate <15%, a false-positive rate <15%, and fixation loss <20%.

Intraocular pressure (IOP) at baseline was defined as the average IOP of 2 consecutive visits in the absence of IOP medication. In patients using IOP medications, IOP was measured 1 month after discontinuing the medications. The average value of IOP medications during the observation period was used as the number of IOP medications.

To be classified as myopia, eyes had to have a spherical equivalent (SE) less than −2.00 diopters and an AL greater than 24.0 mm. Exclusion criteria included eyes with media opacities, such as a corneal opacity, cataract, or vitreous opacity; systemic disease or ocular disease that can affect VF tests; and baseline MD of −20 dB or less, for which glaucoma progression would be difficult to evaluate on VF test. One eye in each patient was randomly selected for inclusion in the study.

Measurement of the Parameters Related to Optic Disc Tilt and Peripapillary Atrophy

Color fundus photography (Topcon, Paramus, New Jersey, USA) was obtained for measurements of the optic disc and β-zone PPA. The photographs were acquired after dilation of the pupil. Images were evaluated by 2 investigators (J.C.H. and E.J.L.) in a masked fashion using ImageJ software (version 1.52; National Institutes of Health, Bethesda, Maryland, USA). The averages of the 2 investigators were used in the final analysis. Disc ovality index was defined as the ratio between the longest and shortest diameters of the optic disc. Optic disc torsion was defined as the deviation of the long axis of the optic disc from the vertical meridian. The vertical meridian was defined as the vertical line 90 degrees from the line that connects the fovea and the center of the optic disc. The presence of β-zone PPA was defined as the region of chorioretinal atrophy with both visible sclera and choroidal vessels adjacent to the optic disc. The areas of β-zone PPA were measured by ImageJ. In the present study, β-zone PPA–to–disc area ratio was used instead of β-zone PPA to minimize the effect of photographic magnification error . When the disc torsional angle was greater than 15 degrees, the case was categorized as inferiorly tilted disc. If this angle was less than 15 degrees, the case was categorized as temporally tilted disc ( Figures 1 ).

Measurement of optic disc tilt and peripapillary atrophy (PPA). (Top) Disc ovality index was defined as the ratio between the longest (blue line) and shortest diameters (blue dotted line) of the optic disc. Optic disc torsion was defined as the deviation of the long axis of the optic disc from the vertical meridian. The vertical meridian (yellow line) was defined as the vertical line 90 degrees to the line that connects the fovea and the center of the optic disc (yellow dotted line). The presence of the β-zone PPA was defined as the region of chorioretinal atrophy with both visible sclera and choroidal vessels adjacent to the optic disc (green dotted line). (Middle) When the disc torsional angle was greater than 15 degrees, the case was categorized as inferiorly tilted disc. (Bottom) If not, the case was categorized as temporally tilted disc.

Definitions of Open-Angle Glaucoma and Visual Field Progression

The following criteria were required for the diagnosis of OAG. First, glaucomatous optic disc changes such as increased cupping (vertical cup-to-disc ratio >0.7), diffuse or focal neural rim thinning, disc hemorrhage, or retinal nerve fiber layer (RNFL) defects had to be present at the time of diagnosis. Second, glaucomatous VF defects positive for at least 2 of the following criteria were required to have been present during more than 1 reliable test: (1) a cluster of 3 points with a probability less than 5% on the pattern deviation map in at least 1 hemifield, including at least 1 point with a probability less than 1% or a cluster of 2 points with a probability less than 1%; (2) a glaucoma hemifield test result outside the normal limits; or (3) a pattern standard deviation of 95% outside the normal limits. Third, an open angle on gonioscopic examination must have been confirmed with no identified cause of secondary glaucoma present.

Progression of glaucomatous VF was defined using Glaucoma Progression Analysis (GPA; Carl Zeiss Meditec Inc) software, which supplies both event-based and trend-based progression analyses. In the event-based analysis, results were regarded as significant ( P < .05) when deterioration was evident on the pattern deviation probability maps at the same 3 or more points on 2 consecutive follow-up tests, and the GPA flagged it as “possible progression.” If significant deterioration was seen at the same 3 or more points in 3 consecutive follow-up tests, the GPA flagged this as “likely progression.” When the VF defect did not adhere to the above, the software flagged “no progression detected.” “Possible progression” and “likely progression” were considered as VF progression. On trend-based analysis, GPA software provides the slope of the change in VFI with respect to time. The VFI is the aggregate percentage of visual function of the eye determined through a linear regression model. The global progression rates were measured using VFI in trend-based analyses.

VF progression patterns such as 1-hemifield-involvement cases and dominant VF defect direction were investigated. A 1-hemifield-involvement case was defined when the glaucomatous VF defect was found in only 1 hemifield. To determine the dominant VF defect direction at the final examination, eyes with more advanced defects in the superior hemifield were classified as superior-dominant defects, and eyes with more severe defects in the inferior hemifield were classified as inferior-dominant defects.

Because we speculated that more asymmetric ONH deformation could induce larger optic disc torsional angle, as reported in previous studies, we compared factors among VF progression pattern groups in myopic OAG with inferiorly tilted disc (larger torsional angle than temporally tilted disc). The VF progression patterns were divided into stationary, progression, and progression-to-stationary groups according to presence of VF progression during the observation period. The progression-to-stationary group was defined as initial progression without further progression for at least 5 VF examinations during the last 3 years of the observation period ( Figure 2 ).

Progression patterns in myopic open-angle glaucoma with inferiorly tilted disc. In the event-based analysis, the results are regarded as significant ( P < .05) when deterioration is evident on the pattern deviation probability maps at the same 3 or more points on 2 consecutive follow-up tests, which the Glaucoma Progression Analysis (GPA) flags as “possible progression.” If significant deterioration is seen at the same 3 or more points in 3 consecutive follow-up tests, GPA flags this as “likely progression.” The “possible progression” and “likely progression” results are considered progression (Top); other results are considered stationary (Middle). The progression-to-stationary group was defined as initial progression without further VF progression during the last 3 years of the observation period (Bottom).

Data Analysis

Intraobserver (2 consecutive measurements by J.C.H.) and interobserver (measured by J.C.H. and Y.K.K.) reproducibility were assessed by calculation of intraclass correlation coefficients (ICCs). Twenty randomly selected fundus photographs and optical coherence tomography images were used for the analysis. Independent t test or Mann-Whitney U test was used to compare variables between nonmyopic OAG and myopic OAG after data normality was assessed. The χ ² test was used to compare categorical data. Continuous variables were expressed as mean ± standard deviation (range). Kruskal-Wallis test and Tukey post hoc analysis were employed for the comparison among nonmyopic OAG, myopic OAG with temporally tilted disc, and myopic OAG with inferiorly tilted disc. Kaplan-Meier analysis and the log-rank test were used to compare survival experiences (time-to-progression event) between nonmyopic OAG and myopic OAG, and we also compared the survival experiences among nonmyopic OAG, myopic OAG with temporally tilted disc, and myopic OAG with inferiorly tilted disc. The hazard ratios (HRs) for the associations between potential risk factors and glaucomatous progression were determined using Cox proportional hazards modeling. Univariate analysis was performed for each factor. Factors with P < .2 on univariate analysis were included in the multivariate Cox proportional hazards model. A backward elimination was used to develop the final multivariate model, and adjusted HRs with 95% confidence intervals (CIs) were calculated.

In myopic OAG with inferiorly tilted disc, when VF progression pattern was classified into progression, stationary, and progression-to-stationary, Kruskal-Wallis test and Tukey post hoc analysis were used to analyze the factors among the 3 characteristic VF progression patterns. The χ ² test was used to compare categorical data. All statistical analyses were performed with SPSS software version 18.0 (SPSS, Inc, Chicago, Illinois, USA). A P value less than .05 was considered statistically significant.