Observational studyPloS one2026
Ten-year natural history of visual function in Japanese patients with Leber hereditary optic neuropathy: A retrospective cohort study.
Observational study in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Leber hereditary optic neuropathy (LHON) is a mitochondrial optic neuropathy that typically causes severe bilateral central vision loss. Although several natural-history studies have reported visual outcomes, long-term trajectories beyond 5 years remain incompletely quantified, particularly in Asian cohorts. We performed a single-center retrospective cohort study at a tertiary eye hospital in Japan. Among 174 genetically confirmed LHON patients, we identified 27 patients (53 eyes) who presented within 6 months of onset and were followed continuously for ≥10 years. Best-corrected visual acuity (BCVA, logMAR) was collected from onset to 120 months. Piecewise linear mixed-effects models with patient- and eye-level random effects were fitted over three phases (Acute, < 12 months; Chronic, 12-60 months; Late Chronic, 60-120 months). Kaplan-Meier analyses estimated time to achieving BCVA ≤1.6 and ≤1.3 logMAR. BCVA worsened rapidly after onset, followed by gradual improvement and then an approximately horizontal course. During the Chronic phase, BCVA showed a small but statistically significant improvement (overall -0.030 logMAR/year, 95% confidence interval (CI) -0.045 to -0.015; -0.025 logMAR/year, 95% CI -0.044 to -0.007 in a pre-specified m.11778G > A subgroup). In the Late Chronic phase, estimated slopes were close to zero (+0.003 logMAR/year, 95% CI -0.007 to +0.013 overall), with wide CIs compatible with small long-term improvement or deterioration. By 10 years, the cumulative probabilities of achieving BCVA ≤1.6 and ≤1.3 logMAR were approximately 45% and 26%, respectively. In this Japanese LHON cohort with ≥10 years of continuous follow-up, BCVA showed limited improvement during the early chronic period, and we did not detect a clear directional trend thereafter. Given the modest sample size and selection of long-term attendees, these estimates should be interpreted as descriptive, phase-specific benchmarks rather than definitive evidence of long-term stability or ethnic differences.
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