Preexisting Fundus Findings in a Large Cohort of Young Cynomolgus Macaques (

purposeTo categorize preexisting fundus findings in a large group of healthy young adult cynomolgus macaques [nonhuman primates (NHPs)] and to compare them to similar conditions in young human retinas.

methodsDuring the past 30 years, more than 20,000 young purpose-bred cynomolgus macaques were screened prior to enrollment in nonclinical pharmaceutical development studies at a single contract research organization. The fundus findings were documented by clinical examinations, various retinal imaging modalities, and/or visual electrophysiological testing.

resultsSheen from the internal limiting membrane (ILM) was common in these young adult NHPs as it is in young humans. Infrequent in both NHPs and humans were cilioretinal arteries. Small patches of retinal pigment epithelial (RPE) depigmentation were common, for which there is no human correlate. Likewise, there is no exact human correlate for foveal drusen-like spots in the young NHPs. Also common in NHPs but uncommon in humans were remnants of the fetal vasculature. Conditions rare in both NHPs and humans included myelinated nerve fiber layer, astrocytic hamartoma, coloboma, and congenital hypertrophy of the RPE. Notable rare abnormal findings included a white dot condition, a large macular tumor, and idiopathic optic atrophy, all of which were of unknown etiology. DISCUSSION: Preexisting abnormalities, when taken together, are common in NHPs and can occasionally complicate the assessment of toxicity from test articles subsequently administered, impacting the clinical development of test articles. As such, it is critical that NHPs be prescreened and, ideally, the fundus appearance be documented with fundus imaging when enrolled in preclinical studies.