Evaluating Visual Function in Zika virus-exposed Macaques with Visual Electrophysiology
Anika Shah, Elaina Razo, Alex Katz, Charlene Kim, Micheal Nork, Karla Ausderau, James Ver Hoeve, Emma MohrAbstract
Background
Feto-maternal transmission of Zika virus (ZIKV) leads to a spectrum of ocular and neurodevelopmental abnormalities. While a variety of structural ocular abnormalities have been identified in ZIKV-exposed infants, the pattern of development of visual abnormalities that manifest later in childhood associated with congenital ZIKV is not well studied. Identifying developmental patterns of visual deficits, even in the absence of structural ocular abnormality, will be beneficial in ZIKV-exposed infants for early detection and categorization of visual deficits to predict and potentially prevent progression of visual disturbances in these infants with intervention.
Methods
Visual function in Indian-origin rhesus macaques (Macaca mulatta) was evaluated through visual electrophysiology by light adapted full-field electroretinogram (ERG) with a contact lens electrode and cortical-derived visual evoked potentials (VEP) with subdermal electrodes. Examination of the eyes by spectral-domain optical coherence tomography and ophthalmic exam assessed retinal structure and pupillary reactivity. Both eyes of 29 ZIKV-exposed infants and 12 infants inoculated with phosphate-buffered saline (control) were analyzed at 3 months and 12 months of age. VEP amplitudes were compared by calculation of the root mean square (RMS) between 0 and 150 milliseconds.
Results
ZIKV-exposed infant macaques had significantly lower VEP amplitudes than control infants at 3 months of age in both left (P=0.0048) and right (P=0.0122) eyes. At 12 months of age, there is no longer a difference in amplitudes. Retinal electrical activity measured by ERG was similar between ZIKV-exposed and control infants. No retinal abnormalities or differences in retinal layer thickness were observed by ophthalmic exam and optical coherence tomography.
Conclusions
These findings indicate infants with prenatal exposure to ZIKV may have delayed cortical maturation even in the absence of structural ocular abnormalities. Cortical visual impairment has a broad spectrum of implications for learning and development. Characterizing early predictors of deficits in cortical development is essential to target effective early interventions and specific therapies.