Normative Values for Multifocal ERGs Recorded from Cynomolgus Macaques in a Non-clinical Setting

Abstract

Purpose : The objective of this study was to obtain normative mfERG data from a large sample of naïve cynomolgus macaques.

Methods : A total of 101 cynomolgus macaques (31 males and 70 females) between 2 and 8 years of age and free of ocular abnormalities provided mfERG recordings as part of baseline pre-treatment data in non-clinical studies. Animals were anesthetized with ketamine and maintained on inhalant sevoflurane. The stimulus was an unstretched 103 hexagonal array presented using an m-sequence with a 13.3 millisecond base rate delivered by the Veris™ FMS system with real-time fundus monitor. For the analysis, the 103 mfERGs were grouped into 6 concentric rings with ring 1 centered on the fovea. Values from hexagons comprising each ring were averaged to yield N1 latency and amplitude and P1 latency and amplitude. For each parameter, mean and cinfidence limits were calculated for males and females for each of the 6 concentric rings.

Results : A complete unilateral mfERG test required approximately 10 min per animal and scoreable recordings were obtained from all 101 animals. As with the ‘stretched’ arrays used in human clinical studies, the unstretched stimuli elicit a large amplitude response from the central element that declines with distance from the fovea. The mean amplitude of the N1 and P1 waves decline to approximately half that of the central element, and the implicit times delayed by half the central element by 10 deg from the fovea, in agreement with our previous studies. Mean N1 and P1 implicit times were significantly longer for females than males across all rings, although absolute differences are small, ~0.5 and 1.0 ms, respectively.

Conclusions : The mfERG assesses local macular function, complementing the global full-field ERG. The use of the mfERG in drug safety studies requires species-specific normal values to sensitively identify abnormal responses. Here we demonstrate the feasibility of recording large numbers of mfERGs in a non-clinical setting and provide confidence limits for mfERGs by sex and foveal eccentricity.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.