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.
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.
Authors: Lisa M Clayton; Marita Devile; Trusjen Punte; Gerrit-Jan de Haan; Josemir W Sander; James F Acheson; Sanjay M Sisodiya Journal: Ophthalmology Date: 2012-07-30 Impact factor: 12.079
Authors: Lisa M Clayton; William M Stern; William D Newman; Josemir W Sander; James Acheson; Sanjay M Sisodiya Journal: Epilepsy Res Date: 2013-03-28 Impact factor: 3.045
Authors: Robert D Fechtner; Albert S Khouri; Emilia Figueroa; Marina Ramirez; Martha Federico; Stephen L Dewey; Jonathan D Brodie Journal: Arch Ophthalmol Date: 2006-09
Authors: Peter Kinirons; Gianpiero L Cavalleri; Dierdre O'Rourke; Colin P Doherty; Irene Reid; Patricia Logan; Brenda Liggan; Norman Delanty Journal: Epilepsia Date: 2006-02 Impact factor: 5.864
Authors: Cinthi Pillai; Robert Ritch; Peter Derr; Alberto Gonzalez; Laurie Kopko Cox; John Siegfried; Jeffrey M Liebmann; Celso Tello Journal: Invest Ophthalmol Vis Sci Date: 2013-04-23 Impact factor: 4.799