Some long-term outcomes of visual dysfunction arising from vigabatrin ocular toxicity

The purpose of this thesis was to assess long-term outcomes of the visual dysfunction arising from the ocular toxicity associated with the anti-epileptic drug vigabatrin (VGB). The risk of vigabatrin-associated visual field loss (VAVFL) with increasing exposure to VGB was modelled from retrospectively collected data from a cohort of 147 individuals (median exposure 7.9 years; IQR 3.6, 11.0). The modelled frequency of VAVFL increased with increasing exposure and plateaued at 75-80% after approximately 6 years duration and 5kg cumulative dose. The relationship between the numbers of retinal ganglion cell soma and axons, derived by standard automated perimetry and time-domain optical coherence tomography (TDOCT), respectively, was evaluated in 24 individuals with VAVFL and in 16 exposed to vigabatrin but with normal fields (VGBN). A strong linear association was present between the two outcomes, which was suggestive of an optic neuropathy, and was similar to the association for a control group of 18 individuals with open angle glaucoma. A follow-up visual field, after a median interval of 7.0 years (IQR 6.5, 7.6) was determined in 19 individuals with VAVFL and in 8 with VGBN, after a median withdrawal from VGB of 7.1 years (IQR 5.4, 8.4). No consistent trend was noted for either a deterioration or improvement in the field. A follow-up scan of the peripapillary retinal nerve fibre layer (RNFL) thickness, by TDOCT, after a median interval of 6.5 years (IQR 5.8, 6.9) was obtained in 13 individuals with VAVFL and in 4 with VGBN, after a median withdrawal from VGB of 8.0 years (IQR 5.3, 10.2). No consistent trend was noted for either a deterioration or improvement of the RNFL thickness. The macular thickness was evaluated by TDOCT in 32 individuals with VAVFL and in 14 with VGBN. No difference in thickness was noted between the two groups