OCT in Neonate Monkeys With and Without Maternal Zika Virus Exposure

Abstract

Purpose : Zika virus (ZIKV) infection in utero can lead to birth defects and neurodevelopmental deficits. The purpose of this ongoing study is to determine if ocular signs of ZIKV infection are apparent shortly after birth in a non-human primate (NHP) model of in utero ZIKA exposure. Non-exposed neonates and those with no evidence of ZIKV infection provide needed age-related OCT data.

Methods : In this first phase, we examined four neonate monkeys, 2 to 5 days of age (D), whose mothers had been infected with ZIKV, and two non-exposed neonates, 7 and 13 D. Four pregnant rhesus macaques were inoculated with 10^4 PFU of a Puerto Rican isolate of ZIKV in the first trimester and monitored closely throughout pregnancy. Neonates underwent anterior segment and retinal imaging with a Heidelberg Spectralis HRA+OCT. Each infant had 60 tissues assessed by PCR for Zika virus and all were negative. One infant had virus at the maternal-fetal interface (decidua) at the time of delivery. Data from this animal were considered separately. Animals were anesthetized, and pupils dilated. EXCELSIOR Preclinical’s functionalities for retinal segmentation (EdgeSelect™) and automated image analysis were used to calculate mean thicknesses for 10 layers, respectively.

Results : Total retinal thickness (TRT) increased with age, from 0.244mm, 0.258mm, 0.260mm to 0.280mm, in animals scanned at 2, 5, 7 and 13 D, respectively (n=1 except 5 D n=2). Outer nuclear layer (ONL) thickness increased from 0.045mm at 2 D to 0.063mm at 13 D. Photoreceptor outer segments (PR-OS) increased from 0.021mm at 2 D to 0.033mm at 13 D. Adult values were 0.278mm, 0.064mm and 0.036mm for TRT, ONL and PR-OS, respectively. Central corneal thickness was up to 72um less in the 2 D than other neonates; all had open angles. The 5 D ZIKV neonate with virus at the decidua had a thinner choroid (0.116mm) than the other two 5 D animals (0.154mm) and the 7 D (0.189mm).

Conclusions : As with humans, in utero exposure to ZIKV did not always result in an affected infant. The infant with exposure at the decidua had a thinned choroid, a finding reported in affected human infants. Definitive statements about the structural sequela of in utero ZIKV exposure will require the full cohort of planned animals. Characterizing ZIKV ocular infection phenotypes and correlating these with viral tissue distribution in this NHP model of congenital Zika infection are important to vaccine and immunotherapy development.

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