Abstract
Purpose :
Glaucoma is a neurodegenerative disease that results in a progressive loss of retinal ganglion cells (RGCs), leading to irreversible blindness. Clinically, visual function in glaucoma is commonly assessed using Standard Automated Perimetry (SAP) within 30° of fixation using a standard white Goldmann size III stimulus. The use of alternative stimulus sizes has been proposed for early detection and monitoring of disease. However, the association between visual thresholds using different stimulus sizes and localized RGC content is unknown. Our study aimed to determine this relationship in the non-human primate experimental glaucoma model.
Methods :
Unilateral experimental glaucoma was induced in 5 rhesus monkeys (Macaca mulatta) who were trained to perform SAP with Goldmann stimulus sizes I through V. Animals were monitored with optical coherence tomography and SAP to varying endpoints, following which they were euthanized and perfusion fixed with 4% paraformaldehyde. Each eye cup was dissected, and 1mm circular retinal punches were obtained from 34 corresponding SAP locations. RGCs were immunolabeled with an antibody against an RNA-binding protein (RBPMS) marker, and imaged using confocal microscopy. RGC counts were estimated for each sampled location based on stimulus size and related to the corresponding endpoint differential light sensitivity (DLS).
Results :
At endpoint, circumpapillary nerve fiber layer thickness in experimental glaucoma eyes ranged from 43 to 74µm. The peak RGC density for control eyes was 18,698 ± 7620 cells/mm2 at an eccentricity of 4.2°, tapering to 2345 ± 1617 cells/mm2 at 27.2°. A segmental two-line fit was the best model that described the relationship between log DLS and log RGC counts (R2 = 0.74, AICc = - 2844, P =0.99).
Conclusions :
In non-human primates, SAP visual thresholds are related to the underlying RGCs. The relationship follows that predicted by spatial summation, and suggests that stimulus parameters for quantifying vision should be based on the stage of disease.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.