ArticleEye (London, England)2026
Clinical features and temporal trends in a large Japanese LHON cohort, 1995-2024: a retrospective study.
Article in Eye (London, England), 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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Abstract
BACKGROUND/
objectivesLeber hereditary optic neuropathy (LHON) exhibits population-specific characteristics in Japan, but long-term temporal changes remain unclear. SUBJECTS/
methodsWe retrospectively analysed 179 patients with genetically confirmed LHON at Inoue Eye Hospital (1995-2024). Age at onset was evaluated using median (τ = 0.5) quantile regression, with temporal effects expressed per decade. Female proportion, m.11778 G > A frequency, and-among adults ( ≥ 20 years)-smoking and alcohol use were assessed using logistic regression. Age-band distributions (10-year intervals) were compared between 1995-2012 and 2013-2024 using a χ² test.
resultsThe median age at onset was 33 years (interquartile ranges, 18.5-48.0); 83.2% were male. Mutation frequencies were m.11778 G > A, 88.8%; m.14484 T > C, 9.5%; and m.3460 G > A, 1.7%. Age at onset increased by 4.29 years per decade (95% confidence interval [CI], 0.16-8.41; p = 0.043). Temporal changes were not significant for female sex (odds ratio [OR]/decade, 1.39; 95% CI, 0.80-2.40; p = 0.24) or for m.11778 G > A (OR/decade, 1.38; 95% CI, 0.74-2.56; p = 0.31). Among adults with available data, smoking showed a nonsignificant decrease and alcohol use a nonsignificant increase; however, these exploratory estimates were limited by missingness, retrospective exposure ascertainment, and complete-case analysis. After 2013, the age distribution shifted (p = 0.0436), with more patients aged 30-49 years, fewer aged 0-9 years, and emerging cases at 70-79 years.
conclusionsAge at onset increased over time, whereas sex ratio and m.11778 G > A predominance remained stable. Wider availability of genetic testing, together with improved recognition of optic neuropathy in routine practice, may have reduced under-recognition in older adults, partly explaining the upward shift in age at onset.
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