Risk factors for ethambutol-induced optic neuropathy: a systematic review and meta-analysis of comparative studies

To identify risk factors for ethambutol-induced optic neuropathy (EON).

Systematic review and meta-analysis.

A literature search was conducted of PubMed, MEDLINE, EMBASE, and grey literature on February 5, 2024. Observational studies describing adults receiving ethambutol with optic neuropathy were included. Extracted data included patient demographics and comorbidities, dose, and duration of treatment with ethambutol, and the number of patients diagnosed with EON. A random-effects meta-analysis was performed for patients with hypertension, and patients with diabetes mellitus. Risk of bias was assessed using the Cochrane's RoB 2.0 tool and ROBINS-I tool. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation.

Eleven studies encompassing 370 patients diagnosed with EON were included. Longer duration of ethambutol therapy and the presence of comorbid renal disease were the most consistently associated risk factors. While non-weight-adjusted dosing did not significantly correlate with EON, patients receiving weight-adjusted doses had significantly higher daily dosages among EON cases. hypertension (odds ratio [OR] = 1.86; 95% CI 0.44-7.75; p = 0.11; k = 2) and diabetes mellitus (OR = 0.85; 95% CI 0.54-1.35; p = 0.27; k = 3), although neither reached statistical significance. The certainty of the evidence was low to very low, with wide confidence intervals and imprecise effects.

EON is most strongly associated with longer ethambutol duration and renal impairment. The contribution of dosage, hypertension, and diabetes requires further investigation. Overall, judicious planning is required to monitor EON as a potential adverse event of antitubercular therapy.