Three main research groups, on 3 continents, have so far reported their initial results regarding gene therapy for the treatment of Leber's hereditary optic neuropathy (LHON),1-3 which is the first described and the most common condition associated with mitochondrial mutations.4 In this issue of the Journal, Lam et al report the results of a Phase 1, single-institution, open-label clinical trial, aiming to assess the dose-dependent safety and efficacy of unilateral intravitreal injection of low, medium, high, or higher dose of AAV2 (Y444,500,730F)-P1ND4v2) in 28 patients with G11778A LHON.1 Patients were divided into 3 groups: chronic bilateral (onset of visual loss of ≥12 months in 1 eye and ≥6 months in the more recently affected eye); acute bilateral (visual loss in both eyes of ≤12 months); and acute unilateral (with only mildly impaired vision in the fellow eye). According to the prespecified criterion of visual acuity change from baseline (best-correct visual acuity change of 15 letters or more on the Early Treatment Diabetic Retinopathy Study ETDRS chart), some patients improved their vision across the 3 groups, that is, not only in the study eye or the fellow eye of the gene therapy participants, but also in eyes of the natural history patients.5 There was no apparent relationship between the injected dose and visual acuity improvement. The low number of included patients provided limited power to robustly evaluate the efficacy of this gene therapy on visual function; as the authors state, “if there is an efficacy effect, it is likely small and not related to the investigational product dose.”