Abstracts

Rationale: Vigabatrin-associated visual field loss is an important safety concern. We describe functional and structural changes in the retina of patients (pts) with refractory complex partial seizures (rCPS) who met highly conservative criteria for potentially clinically significant change (PCS) during adjunctive vigabatrin (VGB) treatment. Methods: VGB-naﶥ pts with rCPS were included in a 12-month, open-label study (NCT01278173) if they had ?-2 seizures/month, failed ?-3 therapies, and could reliably perform ophthalmologic testing. Ophthalmologic assessments were made at baseline (Visit 1), during the first month of VGB treatment (Visits 2 and 3), and at 3, 6, 9, and 12 months. Assessments included change from the average of Visits 1-3 in central visual field, expressed as mean deviation from normal (Humphrey static perimetry), average retinal nerve fiber layer (RNFL) thickness (spectral-domain optical coherence tomography, SD OCT), the National Eye Institute visual functioning questionnaire (NEI VFQ-39). Of 65 total pts, 5 met pre-defined criteria of PCS (including unilateral changes) in perimetry or SD-OCT measures at 2 (confirmed) or 3 (persistent) consecutive visits (Table 1). The 5 pts who met PCS criteria will be summarized; 2 cases are presented here. Results: Case 1: Male age 44 yrs who failed ?-8 previous AEDs and was taking 3 concomitant AEDs (lacosamide, lamotrigine, and pregabalin) upon initiation of VGB. There were PCS changes (>3dB from reference value) in central visual field SITA 30-2 assessments in the right eye on 2 consecutive visits (Day 90 and 215) and in the left eye on Day 527 (Table 2). There were no PCS decreases in RFNL thickness, but there were >20% bilateral increases in RNFL thickening in 2 segments (27.7m nasal superior [right] and 26.7m nasal inferior [left], Day 408), and 1 quadrant (left nasal) on Day 408 (20.7m) and 527 (15.7m). No other abnormalities were detected, and NEI VFQ-39 results suggest the pt did not perceive changes in general health/vision. Case 2: Male age 30 yrs who failed ?-5 previous AEDs and was taking 3 concomitant AEDs (lacosamide, pregabalin, retigabine) upon initiation of VGB. There were PCS changes in the central visual field SITA 30-2 of the left eye on 2 consecutive visits (Days 300 and 416); right eye changes did not meet PCS criteria (Table 2). There were no PCS decreases in RFNL thickening, but there was a >20% increase in right nasal inferior average RNFL thickening on Day 399 (15.7m). No other abnormalities were detected, and NEI VFQ-39 results suggest the pt did not perceive changes in general health/vision. Pt has remained on VGB for >3.5 yrs after study completion and has normal visual fields and no visual complaints. Conclusions: Two pts presented had confirmed PCS visual-field deficits in one eye during the trial. One pt had a provisional event in the other eye, and both had RNFL thickening of unknown clinical significance. No other abnormalities were detected, and neither pt perceived changes in visual function. Funding: Funding: Lundbeck LLC