Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy.
Publication/Presentation Date
7-1-2025
Abstract
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.
Volume
66
Issue
9
First Page
42
Last Page
42
ISSN
1552-5783
Published In/Presented At
Sergott, R. C., Carelli, V., Newman, N. J., Biousse, V., Yu-Wai-Man, P., Vignal-Clermont, C., Josse, C., Taiel, M., Sahel, J. A., Barboni, P., & LHON Study Group (2025). Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy. Investigative ophthalmology & visual science, 66(9), 42. https://doi.org/10.1167/iovs.66.9.42
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40662892
Department(s)
Administration and Leadership
Document Type
Article