Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

Abstract

Purpose : Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid deposits that are characteristic of age-related macular degeneration (AMD). Our goal is to characterize the structural and imaging characteristics of different types of drusenoid lesion in rhesus macaques in vivo, as compared to drusen found in human AMD.

Methods : Aged rhesus macaques (>20 years) underwent complete ophthalmic examination, including dilated funduscopy. Fundus photos of eyes with drusenoid deposits were subjected to grading using the age-related eye disease study (AREDS) system for evaluating AMD lesions in humans. Different ocular imaging modalities, including spectral domain optical coherence tomography (SD-OCT), blue-peak fundus autofluorescence (FAF), and infrared reflectance (IR) were employed to characterize the lesions. Average thickness of retinal layers across the central 3mm were measured by semi-automated segmentation of SD-OCT images through the fovea. Genetic polymorphisms with known association with macular drusen in rhesus monkeys were assessed.

Results : Of 65 aged macaques evaluated, we identified drusenoid deposits in 20 animals (30.7%). These drusenoid deposits were categorized into two classes based on distinct AREDS classification and imaging characteristics – 1) soft drusen (35%) that are larger (up to 250 mm), variable in size, appear as hyporeflective deposits between the retinal pigment epithelium and Bruch’s membrane on SD-OCT, and have variable autofluorescence; and 2) punctate hard deposits (65%) that are smaller (less than 63 mm), more uniform in size, not visible on SD-OCT, and may be hyperautofluorescent. There are no disruption of outer retinal layers overlying either lesion type, no hyperreflective foci, and no significant thinning of any retinal layers when compared to normal eyes. Single-nucleotide polymorphisms in ARMS2 associated with macular drusen in rhesus monkeys occurred with similar frequencies in animals with either type of deposits.

Conclusions : Multimodal imaging revealed some drusenoid lesions in rhesus macaques that resemble typical AMD drusen in humans, but many are punctuate deposits that more likely represent lipoidal degeneration and can be distinguished by OCT and FAF imaging, helping to refine our understanding of drusenoid lesions in rhesus macaques as a model for human AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.