Outer Segment Thickness Predicts Visual Field Response to QLT091001 in Patients with RPE65 or LRAT Mutations

Purpose: To determine whether the degree of change in Goldmann visual fields (GVFs) following oral administration of QLT091001 was related to baseline measures of retinal structure. Methods: Oral QLT091001 was administered once daily for 7 days in all study patients. Comprehensive ophthalmic testing, including spectral-domain optical coherence tomography (SD-OCT), was conducted in 14 patients with Leber congenital amaurosis (LCA) and 18 patients with retinitis pigmentosa (RP) at seven international sites. Average thickness of the outer segment (OS) layer was calculated over central 20 degrees. Both eyes of each subject were evaluated separately. Results: Nineteen of 28 eyes (68%) with LCA and 13 of 36 eyes (36%) with RP responded to QLT091001. Among these responders, the average baseline thickness of the OS layer (central 20 degrees) was 13.5 mu m in the LCA cohort and 11.7 gm in the RP cohort. Nonresponders had average baseline OS thickness of less than 4.6 mu m in both cohorts. The OS thickness in the central 20 degrees was significantly shorter in nonresponders than responders in the LCA cohort (P = 0.01, t-test) and in the RP cohort (P = 0.02, Wilcoxon rank sum test). The OS thickness in the central 20 degrees did not change significantly from baseline during the first 2 months (P = 0.09, t-test, paired). Conclusions: The present findings suggest that there is a close parallel between the thickness of the photoreceptor layer and the potential for functional improvement in these patients. Translational Relevance: SD-OCT thickness in the central retina may be useful for predicting the visual field response in the peripheral retina to QLT091001.