Updated Review of Leber Hereditary Optic Neuropathy

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•• Yuan J, et al. Seven-year follow-up of gene therapy for Leber’s hereditary optic neuropathy. 2020;8:1125–1127. This review conducted in China built on the prior safety profile demonstrated by Guy et al. in 2017, again demonstrated a favorable safety profile of the rAAV2/ND4 intravenous gene therapy over a 7-year period.

•• Yu-Wai-Man P, et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. 2020;12. The REVERSE trial was the first to directly measure efficacy of the rAAV2/ND4 intravenous gene therapy and demonstrated bilateral visual recovery after single eye injection. This suggested a crossing of the therapy to the fellow eye.

•• Newman NJ, et al. Efficacy and safety of intravitreal gene therapy for Leber hereditary optic neuropathy treated within 6 months of disease onset. 2021;128:649–660. The RESCUE trial was similarly designed to REVERSE and demonstrated efficacy of the rAAV2/ND4 intravenous gene therapy in patients with less than 6 months of visual symptoms from LHON.

•• Efficacy & safety study of bilateral IVT injection of GS010 in LHON subjects due to the ND4 mutation for up to 1 year. ClinicalTrials.gov. 2019. https://www.clinicaltrials.gov/ct2/show/study/NCT03293524. Accessed 27 Apr 2022. The REFLECT trial is currently awaiting conclusion and reporting of data in literature. This trial builds on REVERSE and RESCUE’s findings of bilateral visual improvement by studying the efficacy of rAAV2/ND4 intravenous gene therapy injections into both eyes.

•• Biousse V, et al. Long-term follow-up after unilateral intravitreal gene therapy for Leber hereditary optic neuropathy: the RESTORE study. 2021;3:309–315. The RESTORE study demonstrated sustained treatment efficacy and safety of the rAAV2/ND4 intravenous gene therapy up from 96 weeks to 4.3 years.

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