Retinal function and histopathology in rabbits treated with Topiramate

Abstract

Methods: Six rabbits were treated with a daily oral dose of topiramate orally during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition.Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another anti-epileptic drug).

Electronegative electroretinogram associated with topiramate toxicity and vitelliform maculopathy

“…Recently, electronegative ERGs caused by topiramate have been reported in rabbits [5] but there have been no case reports in humans. It is well documented that topiramate causes ocular side effects such as refractive changes and angle closure [6].…”

“…The abnormal b-wave and normal a-wave found in classically defined electronegative ERGs imply photoreceptor inner segment dysfunction with relative sparing of photoreceptor function [5]. The molecular mechanism of topiramate is unknown, but it has been demonstrated to modify several receptor-gated and voltage-sensitive ion channels [7] which may result in accumulation of GABA in the inner segment layer.…”

Topiramate associated non-glaucomatous visual field defects

“…It demonstrated significant reduction in 30 Hz flicker b-wave amplitude. Histopathological review of inner retinal layers exhibited extensive accumulation of GABA [7]. Maculopathy has also been reported as an underlying mechanism in certain cases presenting with visual scotomas [8,9].…”

Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation

“…Topiramate given orally to rabbits may cause a significant reduction in retinal function as demonstrated by the Fig. 1 Visual field testing when the patient came to our attention, 4 months after he began to experience visual loss, showed bilateral cecocentral scotoma changes in the electroretinogram as well as changes in the immunohistology characterized by a severe c-aminobutyric acid (GABA) accumulation in the inner retina [12].…”