Visual field loss in patients with refractory partial epilepsy treated with vigabatrin: final results from an open-label, observational, multicentre study.

Background: Use of the antiepileptic drug vigabatrin is associated with an elevated risk of visual field loss.
Objective: To determine the frequency of, and risk factors for, vigabatrin-attributed visual field loss (VAVFL) in the setting of a large-scale, multinational, prospective, observational study.
Study Design: A comparative, open-label, parallel-group, multicentre study.
Setting: Hospital outpatient clinics at 46 centres in five countries.
Patients: 734 patients with refractory partial epilepsy, divided into three groups and stratified by age (8-12 years; >12 years) and exposure to vigabatrin. Group I comprised patients treated with vigabatrin for > or =6 months. Group II comprised patients previously treated with vigabatrin for > or =6 months who had withdrawn from the drug for > or =6 months. Group III comprised patients never treated with vigabatrin. Patients underwent perimetry at either 4- or 6-month intervals, for up to 36 months. Visual field outcome was evaluated masked to drug exposure.
Intervention: Perimetry.
Main Outcome Measure: The visual field outcome at each of four analysis points: (i) at enrolment (i.e. baseline, all patients); (ii) for patients exhibiting a conclusive outcome at the initial visual field examination; (iii) for patients exhibiting at least one conclusive outcome to the visual field examinations; and (iv) at the last conclusive outcome to the visual field examinations.
Results: Of the 734 patients, 524 yielded one or more conclusive visual field examinations. For Group I, the frequency of VAVFL at the last conclusive examination was 10/38 (26.3%) for those aged 8-12 years and 65/150 (43.3%) for those aged >12 years. For Group II, the respective frequencies were 7/47 (14.9%) and 37/151 (24.5%). One case resembling VAVFL was present amongst the 186 patients in Group III at the last conclusive examination. The frequency of VAVFL in Groups I and II combined was 20.0% for those aged 8-12 years and 33.9% for those aged >12 years. VAVFL was associated with duration of vigabatrin therapy (odds ratio [OR] up to 15.2; 95% CI 4.4, 51.7), mean daily dose of vigabatrin (OR up to 26.4; 95% CI 2.4, 291.7) and male gender (OR 2.51; 95% CI 1.5, 4.1). VAVFL was more frequently detected with static than with kinetic perimetry (OR up to 0.43; 95% CI 0.24, 0.75).
Conclusions: Since the probability of VAVFL is positively associated with treatment duration, careful assessment of the risk-benefit ratio of continuing treatment with vigabatrin is recommended in patients currently receiving this drug. All patients continuing to receive vigabatrin should undergo visual field examination at least every 6 months for the duration of treatment. We recommend two-level (three-zone), gradient-adapted, suprathreshold static perimetry of the peripheral field together with threshold perimetry of the central field out to 30 degrees from fixation. The frequency of ophthalmological and perimetric examinations should be increased in the presence of VAVFL.