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Updated: Feb 19, 2026
Author Spotlight: Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration
Published on: May 26, 2023
In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques
Glenn Yiu1, Eric Tieu2, Christian Munevar3
1Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, California, USA. gyiu@ucdavis.edu.
Abstract:
Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruch's membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates.
Insights
Nonhuman primates develop drusenoid lesions similar to human age-related macular degeneration (AMD). Multimodal imaging revealed two distinct phenotypes, offering insights into AMD development and its absence in advanced stages in these animals.
Area of Science:
- Ophthalmology
- Comparative Pathology
- Primate Models
Background:
- Nonhuman primates share a true macula with humans.
- They spontaneously develop drusenoid lesions, key indicators of age-related macular degeneration (AMD).
- Previous research noted clinical and histopathological similarities between human and nonhuman primate drusen.
Purpose of the Study:
- To characterize drusenoid lesions in aged rhesus macaques using multimodal imaging.
- To identify distinct drusen phenotypes and their association with retinal pigment epithelium (RPE) thickness and genetic factors.
Main Methods:
- Fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) were employed.
- The Age-Related Eye Disease Study 2 (AREDS2) grading system was adapted for lesion classification.
- Rhesus macaque eyes (n=65) were evaluated, with lesions identified in 20 animals (30.7%).
Main Results:
- Two distinct drusen phenotypes were identified: larger soft drusen and smaller hard, punctate lesions.
- Soft drusen appeared as hyperreflective deposits on SD-OCT; hard lesions were often undetectable by SD-OCT.
- Eyes with drusen showed a slightly thicker RPE compared to control eyes (P=0.012).
- Genetic polymorphisms in ARMS2 and HTRA1 showed similar frequencies between phenotypes.
Conclusions:
- Multimodal imaging effectively characterized drusenoid lesions in rhesus macaques.
- The study refines understanding of drusen development and highlights differences in advanced AMD progression compared to humans.
