Meta-analysis of treatment outcomes for patients with m.11778G>A MT-ND4 Leber hereditary optic neuropathy.

Our aim was to assess the visual outcomes of patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A MT-ND4 mutation who had no treatment (natural history) or received idebenone or lenadogene nolparvovec. Efficacy outcomes included clinically relevant recovery (CRR) from nadir and final best-corrected visual acuity (BCVA). For the natural history and idebenone groups, we performed a systematic review of the literature and available clinical/regulatory reports. For the lenadogene nolparvovec group, all data from phase 3 studies were included. The overall effect and its 95 % confidence interval (CI) were estimated using a random effects model. For each meta-analysis, patients had a mean age of approximately 30 years at vision loss and were mostly (≥78 %) men. The CRR from nadir [95 % CI] at eye level was 17 % [7 %; 30 %] (n=316 eyes), 31 % [24 %; 40 %] (n=313) and 59 % [54 %; 64 %] (n=348) in untreated, idebenone-treated and lenadogene nolparvovec-treated patients, respectively. This gradient of efficacy was also observed with CRR at the patient level and final BCVA. There was a gradient of efficacy in all assessed visual outcomes, more marked for CRR than for final BCVA, with lenadogene nolparvovec gene therapy superior to idebenone treatment, and both superior to the natural history of the disease.