This was a cross-sectional study. The subjects consisted of patients with OAG and NAION who visited the Samsung Medical Center (Seoul, South Korea) between December 2015 and March 2021. This study followed all the guidelines for experimental investigation in human subjects and was approved by the Samsung Medical Center Institutional Review Board and adhered to the tenets of the Declaration of Helsinki.
The inclusion criteria of OAG included (1) the presence of glaucomatous optic disc changes, such as increased cupping, diffuse or focal neural rim thinning, disc hemorrhage, or RNFL defect; (2) an open angle on gonioscopic examination; and (3) glaucomatous visual field (VF) defects detected by more than one reliable test for at least two of the following three criteria: (1) a cluster of three points with a probability of less than 5% on the pattern deviation map in at least one hemifield, including at least one point with a probability of less than 1% or a cluster of two points with a probability of less than 1%; (2) a glaucoma hemifield test result outside normal limits; and (3) a pattern standard deviation (PSD) of 95% outside the normal limits. Reliable VF analysis was defined as a false-negative rate of <15%, a false-positive rate of <15%, and a fixation loss of <20%.
The inclusion criteria of NAION included (1) development of painless vision loss within 30 days of documented optic disc swelling confirmed by an ophthalmologist, (2) patient age between 40 and 85 years, (3) VF loss consistent with NAION, and (4) a relative afferent pupillary defect, unless the fellow eye affected in the past or both eyes were simultaneously affected with similar intensity. We only included chronic NAION eyes with a follow-up of at least 6 months after the acute phase. The exclusion criteria of NAION included (1) history or signs of any other intraocular, orbital, or intracranial disease; (2) history of ocular trauma; (3) other types of optic neuropathy suggested by ocular manifestation, history, or blood tests, including arteritic anterior ischemic optic neuropathy (AION), inflammatory optic neuritis, or glaucoma, such as glaucomatous optic disc change or increased IOP; and (4) medication known to affect visual function (e.g., ethambutol, digoxin, and vigabatrin) or to cause miosis (e.g., opioids).
In both diseases, we excluded eyes without βPPA; we only included the eyes with confirmed βPPA on fundus photograph and OCT. Eyes with media opacities and systemic or ocular diseases that could affect the VF test and OCTA were excluded.
Each participant underwent a comprehensive ophthalmic examination, including slit-lamp biomicroscopy, manifest refraction, tonometry, dilated stereoscopic examination of the ONH, color and red-free fundus photography (TRC-50DX model; Topcon Medical System, Inc., Oakland, NJ, USA), automated perimetry using a central 24-2 or 30-2 Humphrey field analyzer (HFA model 640; Humphrey Instruments, Inc., San Leandro, CA, USA) with the Swedish interactive threshold algorithm standard, spectral-domain OCT with Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA), and swept-source OCTA (DRI OCT Triton; Topcon, Tokyo, Japan).
We prescribed IOP-lowering eye drops, depending on the judgment of the treating clinician for each patient. We used combinations or choices of commercially available prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, and α-2 adrenergic agonists, with subsequent additional medication based on clinical judgment. Patients with primary OAG were offered laser trabeculoplasty or glaucoma surgery when medical treatment failed.