Sabril Vision Study: Retinal Structure and Function in Adult Patients with Refractory Complex Partial Seizures (rCPS) Treated with Vigabatrin (S14.004)

Objective: To evaluate visual-field (VF) and retinal-structure changes following adjunctive vigabatrin treatment in vigabatrin-nave adults with rCPS. Background: Visual deficits have been reported in retrospective, cross-sectional studies in vigabatrin-treated patients. Methods: Prospective, longitudinal, single-arm, open-label study (NCT01278173). Eligible patients (≥2 seizures/month who failed ≥3 therapies) performed reliable perimetry (Humphrey automated static) and retinal-structure assessment (spectral-domain optical coherence tomography) pre-vigabatrin exposure. Following vigabatrin initiation, testing occurred within 1 month (reference) and at 3, 6, 9, and 12 months. Endpoints included: mean change from reference in mean deviation (dB) and average retinal nerve fiber layer (RNFL) thickness, visual acuity (VA) changes from baseline, and number of patients who met pre-defined vision-parameter changes at 2 (confirmed) or 3 (persistent) consecutive visits. Results: Sixty-five of 91 screened patients received ≥1 vigabatrin dose (all-patients-treated set [APTS]); 55 had ≥1 valid reference and post-reference assessment (full-analysis set [FAS]). Thirty-six APTS patients with valid pre-/post-reference values completed all planned visits (per-protocol set [PPS]). Thirty-eight (59[percnt]) APTS patients completed the study; 27 (42[percnt]) withdrew (none for VF changes); 32[percnt] and 15[percnt] had abnormal RNFL thinning and VA at baseline, respectively; 20[percnt] had abnormal near VFs vs reference. No significant mean near-VFs changes were observed (PPS); mean change in average RNFL thickness increased significantly (1-year data: Left-eye: 6.37μm, CI:[4.66,8.09]; Right-eye: 7.24μm CI:[5.47,9.01]; PPS). No confirmed 3-line decreases in VA (FAS) were observed; 3 patients had pre-defined confirmed/persistent near-VF changes (FAS). All vision-related AEs were non-serious; the most common was vision blurred (9[percnt]). Conclusions: Prior to vigabatrin initiation, rCPS patients may already exhibit vision deficits. Adjunctive vigabatrin treatment (up to 1-year) did not significantly change population near VFs (despite 3 patients meeting pre-defined near-VF-change criteria). RNFL thickening (unknown clinical significance) was observed. Limitations include: single-arm, open-label design; patients inability to perform ophthalmic/VF examinations; and short-term vigabatrin-exposure duration. Funding: Lundbeck, LLC Disclosure: Dr. Isojarvi has received personal compensation fro activities with Lundbeck LLC. Dr. Sergott has received personal compensation for activities with Biogen-Idec, EMDSerono, Teva, Lundbeck, Pfizer, Thrombogenics, Sanofi-Aventis, Novartis, BioClinica, Covance, Basilea, Heidelberg Engineering, Merck and Co., Glaxo, and United States D Dr. Johnson has received personal compensation for activities with Lundbeck. Dr. Laxer has nothing to disclose. Dr. Wechsler has received personal compensation for activities with Cyberonics, Eisai, Gerson Lehrman Group Inc., Lundbeck, Sunovion, UCB Pharma, and Upsher-Smith. Dr. Dribinsky has received personal compensation for activities with Lundbeck as an employee. Dr. Whittle has received personal compensation for activities with Lundbeck LLC. Dr. Feng has received personal compensation for activities with Lundbeck LLC. Dr. Lee has received personal compensation for activities with Lundbeck as an employee.