A total of 282 subjects; 60 normal subjects, 193 OAG patients, and 29 PXG patients were enrolled and followed-up for at least 36 months at the Department of Ophthalmology of Seoul National University Hospital, from October 2012 to September 2016. The subjects were enrolled in the Macular Ganglion Cell Imaging Study, an ongoing study designed in 2011. All subjects underwent a complete ophthalmologic examination, including visual acuity tests, manifest refraction assessment, slit-lamp examination, IOP measurements using Goldmann applanation tonometry, gonioscopy, dilated fundus examination, color disc photography, red-free RNFL photography (TRC-50IX; Topcon Corporation, Tokyo, Japan), Swedish interactive thresholding algorithm (SITA) 30-2 perimetry (Humphrey field analyzer II; Carl Zeiss Meditec, Jena, Germany), and Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA, USA). The inclusion criteria were age between 20 and 79 years, best-corrected visual acuity of ≥20/40 in the study eye, a refractive error within ±6.00 diopters (D) equivalent sphere, and ±3.00 D astigmatism.
Patients with a history of surgical therapy, such as glaucoma filtering surgery in the study eye, were excluded. However, patients who underwent only cataract surgery were not excluded. Patients with any other ocular disease that could interfere with visual function or any media opacity that would significantly interfere with OCT image acquisition were excluded as well. Patients with any other macular disease that could interfere with segmentation of retinal layers were excluded. Patients also were excluded if no high-quality image could be obtained (i.e., if all of the OCT images showed a signal strength < 6).
Patients with OAG were identified by the presence of glaucomatous optic disc changes with corresponding glaucomatous visual field (VF) defects and an open angle confirmed by gonioscopic examination (>180° visible pigmented posterior trabecular meshwork on nonindentation gonioscopy in primary position). Glaucomatous optic disc changes were defined as neuroretinal rim thinning, notching, excavation, or RNFL defects. Glaucomatous VF defects were defined as (1) glaucoma hemifield test values outside the normal limits, (2) three or more abnormal points with a probability of being normal of P < 5%, of which at least one point has a pattern deviation of P < 1%, or (3) a pattern standard deviation of P < 5%. The VF defects were confirmed on two consecutive reliable tests (fixation loss rate ≤ 20%, false-positive and false-negative error rates ≤ 25%). In this study, OAG was defined above, without the presence of exfoliation in the dilated pupil. OAG in this study means primary OAG. On the basis of baseline IOP (measured at the time of subject's first visit), patients with OAG were divided into two groups in subanalysis: NTG (baseline IOP < 21 mm Hg) and HTG (baseline IOP ≥ 21 mm Hg). PXG in this study was defined additionally to OAG as concomitant with the presence of exfoliation material, a grayish-white material, observed at the anterior lens capsule and/or at the pupillary border with a dilated pupil. All of the glaucoma patients were treated for glaucoma at the discretion of the attending ophthalmologist (KHP), who aimed to reduce baseline IOP by at least 20%. When this was not accomplished, further treatment decisions were made by the treating physician. Patients who needed additional surgical treatment during the follow-up were excluded from this study. Normal individuals were defined as patients with no history or evidence of intraocular surgery except cataract surgery, IOP ≤ 21 mm Hg with no history of increased IOP, the absence of glaucomatous disc appearance, and normal ophthalmologic findings.
All the patients underwent regular follow-up visits 6 months apart, at which time they underwent clinical examination, color disc photography, and red-free RNFL photography. Both eyes were imaged with Cirrus HD-OCT and were examined by standard automated perimetry (SAP) every 6 to 12 months for ≥36 months. For cases in which both eyes met all of the eligibility criteria, one eye was randomly chosen as the study eye prior to the analyses.