Macular thickness measurements of healthy, naïve cynomolgus monkeys assessed with spectral-domain optical coherence tomography (SD-OCT)

Abstract

The purpose of this study was to measure central macular thickness in an unprecedented number of cynomolgus monkeys. Macular thickness was measured with Heidelberg spectral-domain OCT in 320 eyes of healthy and treatment-naïve cynomolgus monkeys (80 males and 80 females). The macula was successfully measured in all 320 eyes. Macular thickness was not significantly different between the sexes. The mean central macular thickness was 244 μm (+/- 21 μm). Macular thicknesses in the quadrants were 327 +/-17 μm (temporal inner), 339 +/- 17 μm (inferior inner), 341 +/- 14 μm (superior inner), 341 +/-18 μm (nasal inner), and 299 +/- 20 μm (temporal outer), 320 +/- 16 μm (superior outer), 332 +/-23 μm (inferior outer), and 337 +/-18 μm (nasal outer). Highly significant differences between the nasal and temporal quadrants were detected. This study successfully demonstrated the feasibility of retinal thickness measurements in healthy cynomolgus monkeys. The present findings indicate that the macula is thicker in cynomolgus monkeys than in humans and provide important normative data for future studies.

Normative Data of Ocular Biometry, Optical Coherence Tomography, and Electrophysiology Conducted for Cynomolgus Macaque Monkeys

“…Parafoveal thicknesses seem to be thicker than those of fovea centers in humans and nonhuman primates. 15 , 39 , 40 The thickness trend on the macula was also observed in our study, except for the GCC. The TRL, IRL, GCL, IPL, INL, OPL, and ONL in the 1- to 3-mm zone (parafovea) was thicker than those in the 1-mm circular zone (fovea), whereas the ORL, NFL, and RPE layers in the 3- to 6-mm zone (perifovea) was thicker than those in the 1-mm circular zone (fovea).…”

“…Using cynomolgus monkeys (aged 30–50 months) of Mauritanian genetic background, Denk et al 40 reported a thicker macular retinal thickness, especially for the parafovea, than that in our study using the same OCT instrument. Except for the foveal thickness (18%), the difference in thickness of each layer was within 10% between the two studies.…”

Selected Aspects of Ocular Toxicity Studies With a Focus on High-Quality Pathology Reports: A Pathology/Toxicology Consultant’s Perspective

“…55,57 Normative macular thickness measurements and common and uncommon spontaneous findings have recently been published for cynomolgus monkeys with SD-OCT using the Spectralis HRA þ OCT Heidelberg platform to aid in distinguishing normal retinal thickness and retina and choroidal features from toxic outcomes in ocular toxicity studies. 69,70 The Heidelberg Spectralis platform is the most commonly used technology for widefield fundus imaging, but the handheld RetCam (Natus Medical) that contacts the ocular surface for widefield fundus color imaging and FA is another device in use at CROs for ocular toxicity studies. In the author's experience, SD-OCT and/or RetCam3 widefield fundus imaging technologies are also useful for tracking location, changing dimensions and appearance, and bioerosion of sustained release technologies, especially biodegradable intravitreal implants and microspheres in dose range ocular toxicity studies, which is important for determining the duration of the recovery phase for GLP ocular toxicity studies, among other useful information for ophthalmologists, pathologists, and toxicologists.…”

A 3D model to evaluate retinal nerve fiber layer thickness deviations caused by the displacement of optical coherence tomography circular scans in cynomolgus monkeys (Macaca fascicularis)

“…Using low coherence interferometry, OCT generates high-resolution cross-sectional images by capturing optical scattering from the tissue and thereby depicting retinal layers, the optic disc, and beyond. In preclinical ophthalmology toxicology studies, OCT has become an indispensable imaging tool enabling non-invasive real-time observation of the retina and optic nerve during the time-course of the study [ 3 , 4 ]. Cynomolgus monkeys are frequently used for safety profiling of new drug candidates.…”

“…Cynomolgus monkeys are frequently used for safety profiling of new drug candidates. Their anatomical similarity to humans, including their congruent eye structure with the presence of the macula and the relatively large eye size compared to other research animals such as rodents renders cynomolgus monkeys suitable model organisms for the safety assessment of ocular compounds during which ocular structures are monitored by OCT [ 3 – 5 ].…”