Postnatal Development of ERG and VEP in Non-human Primates Exposed to Zika Virus

Abstract

Purpose : To describe the development of the light- and dark-adapted (LA, DA) electroretinogram (ERG) and flash cortical visual evoked potential (VEP) in neonatal non-human primates (NHP) as part of a study of the neurologic effects of maternal exposure to Zika virus (ZIKV).

Methods : Subjects were 16 rhesus macaque monkeys, age 5 - 90 days. Nine infants were exposed to ZIKV in utero; the rest served as controls. All animals underwent a complete ophthalmic examination and OCT imaging. For electrophysiologic testing, monkeys were anesthetized with propofol and pupils were dilated. Averages based on 5 or 80 flashes were recorded to 3.0 cd-s m^-2 flashes. LA and DA intensity-response series were also recorded. Data were analyzed using a linear mixed effects analysis and comparisons were adjusted by corrected gestational age (covariate).

Results : As expected, no virus was detected in infants exposed in utero. The neonatal NHP LA ERG to a series of increasing flash strengths consisted of an A-wave and an early OP-like wave, with relatively constant implicit time (IT), followed by a B-wave, with ITs that increased exponentially with log flash strength, unlike the ‘photopic hill’ in adults. The DA ERG intensity series was relatively adult-like. The 5-flash average VEP from the youngest infants (<14 D, N=7) were of extraordinarily large amplitude (> 70 micro-volts) relative to infants 90 D old and adults. In contrast, young infant FVEP averages of 80 flashes became markedly diminished in amplitude and inconsistent relative to the same infant’s 5-flash average. OCT analyses found that the outer segment/interdigitation zone (OS/IZ) and the ONL were thinner and the IPL was thicker in ZIKV-exposed infants vs the controls. In general, neither ERG amplitudes nor fundus appearance distinguished ZIKV-exposed Infants from controls. However, one 30-day-old infant from a mother exposed to ZIKV in a previous pregnancy had a normal ERG but no recordable VEP and was behaviorally blind.

Conclusions : The NHP ERG and VEP undergo marked changes postnatally in both ZIKV-exposed infants and controls. The hyper-amplitude neonatal NHP VEP adapts rapidly and may not be evident with traditional averaging. The neonatal photopic B-wave IT is markedly delayed with increased flash strength. It is important to understand these postnatal changes in order to evaluate the effects of ZIKV exposure.

This is a 2020 ARVO Annual Meeting abstract.