June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Incidental finding of white dots in the central retinas of two young cynomolgus macaques
Author Affiliations & Notes
  • Peter Sonnentag
    Toxicology Study Direction, Labcorp Drug Development, Madison, Wisconsin, United States
  • Carol A Rasmussen
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Yelena Krakova
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
  • Paul Miller
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Charlene B Y Kim
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • James N Ver Hoeve
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Hugh D. Wabers
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
  • Rui Chen
    Baylor College of Medicine, Houston, Texas, United States
  • Christopher J Murphy
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    University of California Davis School of Veterinary Medicine, Davis, California, United States
  • T Michael Nork
    OSOD, Ocular Services on Demand, Madison, Wisconsin, United States
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Peter Sonnentag Labcorp Drug Development, Code E (Employment); Carol Rasmussen None; Yelena Krakova None; Paul Miller None; Charlene Kim None; James Ver Hoeve None; Hugh Wabers None; Rui Chen None; Christopher Murphy None; T Michael Nork Research to Prevent Blindness (RPB) , Code F (Financial Support)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4420 – F0099. doi:
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    • Get Citation

      Peter Sonnentag, Carol A Rasmussen, Yelena Krakova, Paul Miller, Charlene B Y Kim, James N Ver Hoeve, Hugh D. Wabers, Rui Chen, Christopher J Murphy, T Michael Nork; Incidental finding of white dots in the central retinas of two young cynomolgus macaques. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4420 – F0099.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize the morphology and functional aspects of an unusual incidental finding in two treatment-naïve cynomolgus macaques.

Methods : Animal #1 was a 2.8 kg, 2.67-year old male of Cambodian origin. Animal #2 was a 3.9 kg, 7.75-year old female of Chinese origin. Both animals underwent clinical ophthalmoscopic examination, color fundus photography, spectral domain optical coherence tomography (OCT), blue (BAF) and infrared (IRFA) fundus autofluorescence, fluorescein angiography (FA), full field electroretinography (ERG), and flash visually evoked potentials (fVEP). Animal #1 also had genomic analysis conducted to assess for known molecular mutations.

Results : Both animals had normal anterior segments including corneas, lenses and vitreous. No cell or flare was noted. Animal #1 had numerous prominent white spots in the macula (Figure 1) and extending peripherally to about 2 disc diameters beyond the nasal margin of the optic disc and the arcade vessels in both eyes. The peripheral retina was unremarkable. FA showed the spots to be window defects, i.e., early hyperfluorescence with late fading but no leakage. The spots were hyper-BAF, hypo-IRAF. OCT showed thickening at the interdigitation zone (IZ) (Figure 2). Animal #2 had fainter spots, but the size and distribution were similar to Animal #1. Except for the fundus findings, both animals were otherwise healthy. Scotopic and photopic ffERG and fVEP were normal. Whole genome sequence analysis of Animal #1 was negative for EFEMP1 (Doyne’s), RDH5 (albipunctatus) and RLBP1 (retinitis pigmentosa).

Conclusions : We have not observed similar white spots in the thousands of cynomolgus macaques examined over the past two decades. Thus, the finding is rare in our cohort of animals. There is no obvious human correlate to these spots. They appear to be functionally benign and are not associated with inflammation. The spots were fainter in the older animal, which could indicate fading over time or just be individual variation. Yiu, et al (Sci Rep 2017;7:1513) reported drusenoid lesions in rhesus macaques but the OCT thickening in our animals is in the IZ, not at Bruch’s membrane. These findings illustrate the importance of baseline ocular examinations in preclinical toxicity studies.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1: Color fundus photo showing white dots in Animal #1.

Figure 1: Color fundus photo showing white dots in Animal #1.

 

Horizontal OCT scan through the same eye that is normal except for focal thickening in the IZ.

Horizontal OCT scan through the same eye that is normal except for focal thickening in the IZ.

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