Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy. METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable. RESULTS: In 113 eyes treated at least 6 months after disease onset, the covariates statistically significantly associated with an improvement in final BCVA after having reached a nadir were thicker OCT measurements at baseline-specifically, outer segments of the macular ganglion cell layer (GCL) (superior, temporal, inferior, and nasal) and retinal nerve fiber layer (RNFL) quadrants (superior, inferior, and nasal) (P < 0.05). The largest effects were observed in the thickness of the superior outer GCL segments at baseline (-0.28 logMAR; 95% confidence interval [CI], -0.41 to -0.16) and temporal outer GCL segments at baseline (-0.26 logMAR; 95% CI, -0.38 to -0.13; both P < 0.001). A better baseline BCVA in the dynamic phase of the disease was associated with a better final BCVA (-0.09 logMAR; 95% CI, -0.11 to -0.08; P < 0.0001). CONCLUSIONS: Better baseline BCVA values and baseline thicker GCL and RNFL at OCT measurements are key predictive factors of the improved BCVA 1.5 years after treatment in patients with MT-ND4 LHON who received lenadogene nolparvovec at least 6 months after disease onset.