Abstract
Purpose :
To determine whether Zika virus (ZIKV) exposure (ZVE) during pregnancy in a non-human primate (NHP) model alters non-invasive measures of visual function.
Methods :
Pregnant rhesus macaques were inoculated with ZIKV from Puerto Rico or Africa during the first trimester. Cesarean-delivered ZVE infants were compared with sham-injected controls. Infant assessments included: neurobehavioral evaluation, ophthalmic examinations (OE), optical coherence tomography (OCT) of the anterior and posterior retinal segments, electroretinography (ERG) and flash visual evoked potentials (FVEP). Additional details have been previously described (Koenig et al, PLOSOne, 2020). Functional assessment included serval classes of tests: photopic and scotopic ERG v. flash intensity series, monocular FVEP and 30 Hz flicker harmonics. Predictor variables included standard A- and B-wave measures, Naka-Rushton (N-R) fits, and FFT harmonics of flicker ERG and oscillatory potentials (OPs). Logistic regression was used to analyze the relationship between electrophysiologic measures and the probability of ZVE. Models using variables to predict exposure were evaluated within and across classes of electrophysiologic test at postnatal ages of 45, 90, and 360 days.
Results :
No abnormalities in OE or OCT were noted in ZVE infants. At 45 days of age (N= 12 controls, 14 exposed), the likelihood of ZVE was higher in individuals with larger photopic A-wave amplitudes and longer implicit times. At 90 days of age (15 controls, 27 exposed), amplitude of the photopic B-wave, photopic negative response and FVEP predicted ZVE. At 360 days (18 controls, 26 exposed), models from several test classes significantly predicted ZVE including, amplitude of photopic monocular FVEP, 30 Hz ERG, and 30 Hz VEP; the goodness-of-fit of the N-R model for the photopic series FVEP; 30 Hz F3 ERG and F3 FVEP amplitude, and photopic and scotopic OPs. A model using the best predictors of ZVE from within each class significantly predicted ZVE (p < 0.01) with an AUC of 0.878, sensitivity of 0.846 and specificity of 0.722.
Conclusions :
Although few abnormalities were noted in OCT imaging or OE, non-invasive functional measures were found that predicted ZVE status at each age. This suggests there are early and long-term sub-clinical changes in the retina and central visual pathways of ZVE infants.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.