Incidence and Clinical Characteristics of Ethambutol-Induced Optic Neuropathy Among Tuberculosis Patients Receiving Directly Observed Treatment: A Prospective Cohort Study

Abstract

Background: Ethambutol, a first-line anti-tubercular drug, is associated with ethambutol-induced optic neuropathy (EON), a potentially irreversible toxic mitochondrial optic neuropathy. The incidence and clinical characteristics of EON differ among populations, yet prospective data from Pakistan remain limited. Objective: To determine the incidence and clinical characteristics of ethambutol-induced optic neuropathy in tuberculosis patients undergoing directly observed treatment, using serial ophthalmological assessments. Methodology: This prospective observational cohort study was conducted at Liaquat University Hospital, Hyderabad, Pakistan, from January 2023 to December 2024. A total of 480 tuberculosis patients initiating ethambutol-containing therapy under DOTS were enrolled. Baseline ophthalmological assessments included best-corrected visual acuity, color vision testing, visual field examination, optic disc evaluation, and optical coherence tomography (OCT). Results: Among 452 participants who completed follow-up, 9 developed EON, corresponding to an incidence of 1.99% (95% CI: 0.92%–3.76%). The mean time to symptom onset was 4.2 ± 1.6 months. All cases were bilateral. Color vision abnormalities occurred in 77.8% of cases, and visual field defects in 88.9%. OCT demonstrated significant increases in average, temporal, and nasal retinal nerve fiber layer thickness (p<0.05). Diabetes mellitus (OR: 3.42; p=0.014) and renal impairment (OR: 4.86; p=0.008) were identified as independent risk factors. Conclusion: EON developed in approximately 2% of tuberculosis patients receiving ethambutol under DOTS. Diabetes mellitus and renal impairment were independent risk factors. Systematic ophthalmological monitoring, especially for high-risk patients, is essential for early detection and prevention of irreversible visual loss.