The Relationship Between Optic Nerve Cup-to-Disc Ratio and Retinal Nerve Fiber Layer Thickness in Rhesus Macaques

Abstract

Purpose : Increased cupping is a sign of glaucomatous optic neuropathy. It is clinically measured using the cup-to-disc ratio (CDR). Similarly, retinal nerve fiber layer (RNFL) loss is associated with disease severity. Due to the similarities in their visual systems and anatomy to humans, rhesus macaques (Macaca mulatta) often serve as a model in ophthalmology research. The purpose of this study was to evaluate the relationship between RNFL thickness and cupping in adult rhesus macaques.

Methods : A total of 52 adult animals were studied (42 females and 10 males), from all ages (range 3.3 to 25.6 years old), which were part of two social groups with high rates of ocular pathologies previously identified. Animals underwent a comprehensive eye exam, including slit-lamp biomicroscopy, pachymetry, axial length measurement, fundus photography and optical coherence tomography (OCT). CDR was determined independently by two experienced glaucoma specialists in a masked fashion from non-stereoscopic digital fundus images. The circumpapillary global and quadrant RNFL thickness was analyzed using a custom automated segmentation software. Eyes were also grouped into those with low CDR (<0.5) and those with high CDR (≥0.5). The relationship of CDR and RNFL was investigated by multilevel mixed-effects models adjusted for axial length, age, and weight.

Results : CDR ranged from 0.2 to 0.75. No statistically significant effect was detected for axial length (mean 19.57±0.57 mm), age (mean 14.5±3.3 years), weight (mean 10.6±2.9 kg) or CDR on RNFL thickness. When eyes were grouped by their CDR, no significant correlation was detected between CDR and global RNFL thickness. However, a significant correlation between CDR and RNFL thickness in the superior quadrant was found (r =-0.068, p < 0.05). Similar correlations were not detected for RNFL thickness in the inferior, nasal or temporal quadrants.

Conclusions : Higher cup-to-disc ratio is associated with increased superior RNFL loss in rhesus macaques. The CDR in rhesus macaques is likely smaller than in humans, even in animals with substantial RNFL loss, which should be tested in future studies.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.