Modelling the Risk of Visual Field Loss Arising from Long-Term Exposure to the Antiepileptic Drug Vigabatrin: A Cross-Sectional Approach

Background: The antiepileptic drug vigabatrin has been used widely since 1989, but has only been approved for use in the US since 2009. The risk:benefit of vigabatrin is generally predicated upon an assumed frequency of associated visual field loss (VAVFL) of approximately 31 %. This estimate is based upon relatively short-term usage (up to 4–5 years) and it is essential to determine whether the frequency of VAVFL increases with longer-term usage. Objective: The aim of this study was to model, from cross-sectional evidence, over greater ranges of treatment duration and cumulative dose than previously evaluated, the risk (frequency) of VAVFL with increasing exposure to vigabatrin. Study Design and Setting This was a retrospective cohort study undertaken in a regional hospital epilepsy clinic. Patients: The cohort comprised 147 consecutive patients treated with vigabatrin for refractory complex partial (focal) seizures, who had all undergone ophthalmological examination and who had undertaken perimetry, reliably, according to a standard and robust protocol. The visual field plots were evaluated masked to treatment duration and dose. Main Outcome Measure: The risk (frequency) of VAVFL with increasing exposure to vigabatrin was modelled, from the cross-sectional evidence, by standard and plateau logistic regression. Results: The cohort comprised 80 females and 67 males (mean age 40.3 years, standard deviation 13.7). The median duration of vigabatrin exposure was 7.9 years (interquartile range 3.6–11.0, range 0.2–16.1 years); 46 patients (31 %) had received vigabatrin for over 10 years. Eighty-seven patients (59 %) exhibited VAVFL; the proportion with VAVFL was higher in males (66 %) than females (54 %). The plateau model for duration and for cumulative dose exhibited a better fit than the standard model (both p < 0.001). The modelled frequency of VAVFL increased with increasing exposure up to approximately 6 years duration and 5 kg cumulative dose, and plateaued at approximately 76 % (95 % CI 67–85) and 79 % (95 % CI 70–87), respectively. Severity of VAVFL, classified in terms of the visual field index Mean Deviation, was not significantly associated with either duration or cumulative dose of therapy. Conclusion: Clinicians and patients, in enabling informed choice, should be alert to the possible substantial increased risk:benefit for VAVFL with increasing long-term exposure to vigabatrin and the ensuing increased cost:benefit resulting from the necessary additional visual assessments