Ten-year natural history of visual function in Japanese patients with Leber hereditary optic neuropathy: A retrospective cohort study

by Yasuyuki Takai, Akiko Yamagami, Mayumi Iwasa, Kenji Inoue, Ryoma Yasumoto, Hitoshi Ishikawa, Masato Wakakura 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, 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.