Prognostic factors for visual acuity in patients with Leber's hereditary optic neuropathy after rAAV2‐ND4 gene therapy

Abstract

Importance Factors affecting visual acuity prognosis after gene therapy in Leber's hereditary optic neuropathy (LHON) patients with mutation at site 11 778 are unknown. Background To analyse correlations between visual acuity prognosis and baseline characteristics of LHON after rAAV2‐ND4 gene therapy. Design Retrospective study. Participants Fifty‐three LHON patients with a mutation at site 11 778. Methods Single‐eye intravitreal injection of rAAV2‐ND4. Main Outcome Measures Sex, onset age, duration of disease, best‐corrected visual acuity (BCVA), visual field index (VFI) and mean deviation (MD) were recorded for all patients at baseline. BCVA was recorded at 1‐ and 3‐month follow‐up visits after gene therapy. Correlations between BCVA prognosis and baseline characteristics were analysed by univariate analysis. Logistic regression analysis was performed on independent factors affecting BCVA prognosis. Results Univariate analysis showed significant differences in the VFI and MD of the injected eye between BCVA improvement and non‐improvement groups after 3 months of treatment, with greater VFI and smaller absolute MD in the BCVA improvement group. Logistic regression showed that VFI and baseline BCVA were independent prognostic factors for visual acuity. The correlation between VFI and MD was statistically significant. Conclusions and Relevance VFI and baseline BCVA were correlated with the visual acuity prognosis of LHON patients receiving gene therapy, with greater baseline VFI and better baseline BCVA predicting better visual acuity prognosis. MD was strongly correlated with VFI and might be correlated with gene therapy prognosis. This finding may form a basis for predicting the efficacy of gene therapy in these patients and guiding subsequent treatment.

A Single-Arm, Prospective, Exploratory Study to Preliminarily Test Effectiveness and Safety of Skin Electrical Stimulation for Leber Hereditary Optic Neuropathy

“…At three months after injection, they found significant differences in baseline visual acuity and visual field index, but not age at onset, between the groups with and without a three-line improvement in logMAR. Logistic regression analysis confirmed that only baseline visual acuity and visual field index were significant in the visual acuity improvement [31], indicating no role for age at onset.…”

Therapeutic Options in Hereditary Optic Neuropathies

“…The first included 142 LHON patients with the m.11778G>A/ MTND4 mutation, 69 more than 24 months after onset and 73 less than 24 months prior to onset; BCVA and VF were the primary outcomes and the final results are expected soon. Retrospective studies on the injected patients showed that greater VF index, smaller VF mean deviation and higher BCVA at baseline predicted a better VA prognosis [ 181 ], and that baseline BCVA and time between onset and treatment are predictors of rapid visual improvement, in both injected and not-injected eyes [ 182 ]. To explain the rapid recovery, within days after treatment, it has been suggested that in some patients a portion of RGCs survive in a “dormant” state that can be activated by gene therapy [ 179 ].…”

Gene therapy for inherited retinal diseases

“…The sponsor of this study, Huazhong University of Science and Technology, is conducting a larger phase II/III study with 142 subjects to confirm the promising safety, efficacy, and durability of rAAV2-ND4 gene therapy (NCT03153293). Initial 3-month results of this larger scale study looked at the baseline functional characteristics that correlated with visual recovery (82). Better baseline visual field index (VFI) and BCVA were found to be strong predictors of functional improvement (82).…”

“…Initial 3-month results of this larger scale study looked at the baseline functional characteristics that correlated with visual recovery (82). Better baseline visual field index (VFI) and BCVA were found to be strong predictors of functional improvement (82).…”