Retinal nerve fiber layer thinning as a measure of cognitive decline in nonhuman primates

Abstract

Purpose : Retinal nerve fiber layer (rNFL) thinning may correlate with cognitive decline in humans, but no similar association has been shown in a large animal model that enables preclinical testing of novel therapies. The aim of this study is to evaluate any associations between RNFL thickness and cognitive performance in rhesus macaques.

Methods : We performed optical coherence tomography (OCT) imaging on animals that underwent a series of cognitive behavioral tasks to test rational decision-making, working memory, and sequence memory. Animals were also assessed for visual acuity by evaluating looking behavior at 2 m, 1m, and 0.33m. Macular OCT images were analyzed by image segmentation using DOCTRAP software to measure the average thickness of the rNFL, and ganglion cell and inner plexiform layers (GCL+IPL) within the nasal 1-3mm and 3-6 mm sector of the Early Treatment of Diabetic Retinopathy Study (EDTRS) grid. To prevent confounds between visual capacity and cognitive performance, relations among cognitive tests and retinal layers were conducted using multiple stepwise regression, controlling for age, testing condition, and visual acuity scores.

Results : We evaluated 90 left eyes (OS) of 90 rhesus macaques (mean age 19.86 years, standard deviation ± 3.28). Retinal layer thickness predicted better performance on most cognitive tests. Reaction time on a rational decision-making test was slower (F (1, 88) =23. 659, p < .001, adjusted R² = .340) and more variable across trials (F (1, 88) = 14.749, p < .001, adjusted R² = .236) in individuals who had thinner NFL layers, suggesting poorer decision-making abilities.

Conclusions : Retinal nerve fiber layer thinning may be correlated with cognitive decline in rhesus macaques, similar to human subjects, highlighting the possibility of using OCT image biomarkers as a measure of cognitive function.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.