Abstracts

Rationale: Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been limited by reports linking VGB exposure to retinotoxicity with rates of irreversible peripheral field vision loss in the range of 30 to 50% (Maguire et al, 2010). However, these studies have focused on older children and adults and may not generalize to younger populations. As these reports conflicted with our clinical observations in routine practice, we sought to systematically review the experiences of patients treated with VGB at UCLA and specifically estimate the incidence of clinically significant vision loss among our patients. Methods: We retrospectively identified patients with video-EEG confirmed infantile spasms who were evaluated at UCLA between February, 2007 and February, 2014. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on review of serial neurologic and ophthalmologic reports, and aided by electroretinography assessments when available, we ascertained whether each patient had evidence of clinically-significant vision impairment (sufficient to be recognized by neurologists or ophthalmologists at any follow-up visit), and whether or not vision loss was plausibly linked to VGB exposure. Results: During the study period, 258 patients with video-EEG confirmed infantile spasms were identified. 143 (55%) patients received VGB, though adequate records detailing the dates of therapy and exact dosages were present for only 104 (73%). The vast majority of patients without adequate documentation of exposure received VGB prior to UCLA evaluation. For the 104 patients, median age at treatment onset was 10.8 (interquartile range 7.1 - 22.3) months, median duration of therapy was 8.5 (3.7 - 16.1) months, median follow-up was 29.6 (14.8 - 48.8) months, median peak dosage was 141.5 (105.0 - 165.7) mg/kg/day, and median cumulative dosage was 314.0 (143.6 - 643.7) grams. Although vision loss was identified among 28 (26.9%) patients, there were no cases in which visual defects were plausibly linked to VGB. Vision loss was never characterized as exclusively peripheral, and was uniformly explained by other causes (e.g. hemianopsia after hemispherectomy, cortical vision loss accompanying hypoxic-ischemic injury, etc). Conclusions: In contrast to prior studies reporting high rates of vision loss among VGB-exposed children and adults, this study estimates that among children treated for infantile spasms the risk of clinically significant vision loss is quite low. The reason for this discrepancy is unclear but likely reflects our approach to ascertain meaningful vision impairment, and suggests age-specific differences in retinotoxic susceptibility. Key limitations in this study include the retrospective design and the inability to conduct formal visual field assessments in this population. Disclosure: This study was funded as an investigator-initiated study by Lundbeck, LLC.