The long-term effects of antiepileptic drugs on the visual system in rats: Electrophysiological and histopathological studies

Objective: We quantified the long-term effects of antiepileptic drugs (AEDs) on the visual system of rats using electroretinograms (ERGs) and visual evoked potentials (VEPs). Methods: Twenty adult Sprague-Dawley rats were divided into 4 groups (n = 5). Each animal was treated by monotherapy of phenytoin (PHT), valproic acid (VPA), zonisamide (ZNS) or physiological saline as control. The AEDs were injected intraperitoneally daily for 180 days. ERGs and VEPs were recorded before the medication and on Days 30 and 180. Results: There were no significant changes in the 4 groups on Day 30. On Day 180, the amplitudes of a- and b-waves of dark-adapted (DA) ERGs were reduced in the PHT group compared with those of the control group. In the VPA group, the amplitudes of the DA ERG a- and b-waves, light-adapted ERG b-wave and the DA VEP were reduced. No significant changes were observed in the ZNS group. There were no histopathological changes of the retina and visual cortex in all groups. Conclusions: Our results indicate that neurons along the visual pathways have different sensitivity to each AED. This may result from the differential pharmacological actions of each AED on visual neurons. Significance: Our findings suggest that epileptic patients on long-term use of AEDs might have subclinical influences to the visual systems.