Document Type

Article

Publication Date

7-15-2025

Comments

This article is the author’s final published version in Investigative Ophthalmology and Visual Science, Volume 66, Issue 9, 2025, Article number 42.

The published version is available at https://doi.org/10.1167/iovs.66.9.42. Copyright © 2025 The Authors

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.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Supplement 1.pdf (188 kB)

PubMed ID

40662892

Language

English

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