Optic neuropathy and ethambutol exposure in a declining tuberculosis population: a nationwide cohort study in Korea

Although global tuberculosis (TB) incidence has declined, ethambutol (EMB) remains a key component of first-line therapy and may cause potentially irreversible ethambutol-induced optic neuropathy (EON). However, large-scale population-based evidence on long-term trends in optic neuropathy diagnoses and on associations between documented EMB exposure and subsequent optic neuropathy is limited. Patients diagnosed with tuberculosis from 2002 to 2013 were identified using the Korean National Health Insurance Service database. A control group without tuberculosis was included, and propensity score matching was performed. The incidence and risk of optic neuropathy were analyzed using multivariable Cox proportional-hazard models, adjusting for age, sex, comorbidities, and EMB exposure, including daily dose and treatment duration. Among 31,175 TB patients and 84,522 matched controls, optic neuropathy incidence was significantly higher in the TB group (adjusted HR 1.28, 95% CI 1.05–1.56). The risk of optic neuropathy rose dose-dependently with EMB: HR 1.94 for < 10 mg/kg/day, 2.98 for ≥ 10–<15 mg/kg/day, and 6.98 for ≥ 15 mg/kg/day. Older age (≥ 50 years) was also associated with an increased risk (HR 2.27; 95% CI 1.84–2.79). Despite a steady decline in TB incidence, the number of optic neuropathy diagnoses increased markedly after 2009. This nationwide cohort shows an increase during the study period in the number of optic neuropathy diagnoses even as TB prevalence declined. Older age and higher EMB dose were associated with a higher risk of claims-defined optic neuropathy. Strengthened pharmacovigilance and regular ophthalmic monitoring should be integrated into TB management to prevent irreversible vision loss.