Vigabatrin visual toxicity:: Evolution and dose dependence

Purpose: To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment, to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs. Methods: A cohort of 155 presurgical candidates who had undergone full-field Goldmann perimetry (GP) was studied, 99 (64%) of whom had been treated with VGB. All GPs were reevaluated in 1998 by one experienced examiner, blinded to medication. Duration of treatment and total VGB dose were related to perimetric results. Results: Twenty-five (16%) of the 155 patients had VFDs: Nineteen (19%) of the 99 VGB-treated patients, and six (11%) of the 56 patients unexposed to VGB. VGB-treated patients with VFDs had been treated significantly longer than those without VFDs. Cumulative VGB dose could be calculated for 84 patients. The prevalence of VFDs increased significantly with increasing total VGB-dose, from 4% in the 51 patients who had been exposed to less than or equal to1 kg VGB, to 75% in the eight patients with a total dose of 3-5 kg of VGB. Sixteen VGB-treated patients were reexamined 2-10 years later. In the 12 where evaluation was possible, all still had VFDs, which had worsened in five cases (42%) and improved in none. Conclusions: This study indicates a strong relationship between VFDs and duration and total dose of VGB. VFDs were irreversible and in a substantial percentage progressive. Similar VFDs may, however, also be found in patients unexposed to VGB. A model of the evolution of the VFDs in VGB toxicity is introduced, and a new simple visual field test is proposed.