Predictive factors of final visual outcome in patients with leber hereditary optic neuropathy treated with lenadogene nolparvovec gene therapy
Piero Barboni, Nancy Newman, Valérie Biousse, Patrick Yu‐Wai‐Man, Valerio Carelli, Catherine Vignal‐Clermont, Constant Josse, Magali Taiel, José‐Alain Sahel, Robert SergottAims/Purpose: To identify the predictive factors of final best‐corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) due to the m.11778G>A MT‐ND4 mutation who received lenadogene nolparvovec gene therapy in clinical studies.
Methods: The following covariates were studied to identify those that might influence 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. In RESCUE and REVERSE, ND4‐LHON patients received an injection of gene therapy in one eye and a sham injection in the other. In REFLECT, the first‐affected eye received gene therapy, while the other eye was randomly injected with gene therapy or placebo.
Results: In 290 untreated/treated eyes, the covariates statistically significantly associated with an improvement in final BCVA were a longer time from vision loss to treatment (p < 0.05), and thicker optical coherence tomography (OCT) parameters at baseline: ganglion cell layer (GCL) temporal outer segment, GCL superior outer segment, GCL nasal outer segment, and GCL inferior outer segment at ETDRS analysis, and retinal nerve fiber layer (RNFL) inferior quadrant, RNFL nasal quadrant and RNFL superior quadrant (p < 0.05). The greatest effects [95% confidence interval] were observed for the thickness of the inferior and superior outer GCL segments at baseline (‐0.1 [‐0.163; ‐0.037] and ‐0.09 [‐0.146; ‐0.033], respectively; both p = 0.002). A worse baseline BCVA was associated with a worse final BCVA (p < 0.0001).
Conclusions: Timing of treatment administration, baseline BCVA value and baseline thickness of OCT parameters are predictive of the BCVA 1.5 years after treatment in patients with MT‐ND4 LHON who received lenadogene nolparvovec.