Abstracts

Rationale: Vigabatrin (VGB) was approved in the US in 2009 as adjunctive therapy for adult patients (pts) with refractory complex partial seizures (rCPS) who had inadequately responded to several alternative treatments, and as monotherapy for pts 1 month to 2 years of age with infantile spasms. An important safety issue for VGB is the risk of vision loss, characterized by bilateral concentric constriction of visual fields in ?30% of pts. Robust data assessing incidence of changes early in treatment are lacking. To define incidence and magnitude of changes in retina structure and function, we are designing a prospective, 1-year open-label trial of VGB as adjunctive therapy for adults with rCPS. Methods: An estimated 80 pts with rCPS ?1 years (with ?2 seizures per month averaged over prior 3 months) will be enrolled at ~25 sites over 18 months. Pts ?18 years of age na ve to VGB will receive open-label VGB therapy at dosages determined by the investigators following guidance in the US product label. Pts must have failed ?3 prior therapies for lack of efficacy and must be receiving concomitant anti-epileptic drugs. Automated kinetic and static perimetry assessments will be conducted at baseline, and 3, 6, 9, and 12 months following initiation of VGB. Retinal structure will be evaluated at the same time points through optical coherence tomography (OCT). Key endpoints will include mean change from baseline in visual field width (kinetic perimetry); change from baseline in mean deviation of visual field (static perimetry); and mean change from baseline in retinal nerve fiber layer thickness (OCT). Secondary evaluations will include visual acuity and color vision, changes in ophthalmologic parameters as functions of time and exposure to VGB, and assessments of physical function, quality of life, and vision-related symptoms. Safety of VGB will be evaluated via ophthalmologic assessments, physical examinations, neurologic examinations, and ongoing adverse event assessment. All pts who receive at least one dose of VGB will be included in all safety analyses. Results: After commencing VGB therapy, pts will be assessed every 3 months through static and kinetic perimetry, OCT, visual acuity, and color vision tests. This study will not mandate VGB discontinuation based on visual field results. If a deficit is discovered, the investigator will conduct a benefit/risk assessment and discuss with the patient. If VGB is discontinued, one final examination will occur, 3 months after discontinuation. If a >10% decrease in the horizontal extent of visual field of either eye for a given patient (compared with previous examination) is detected, perimetry tests will be repeated within 2 weeks to confirm the change. Conclusions: This study is designed to address 2 unresolved issues of VGB-induced vision loss 1) a better definition of onset and progression, and risk of developing vision loss during the first year of VGB exposure, and 2) a robust and more widely available methodology than perimetry for monitoring retinal changes in pts receiving VGB.