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.