Ethambutol optic neuropathy in the extended anti-tubercular therapy regime: A systematic review

The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating optic neuropathy in extended ethambutol use since 2010 and compared the outcome with a similar systematic review (1965-2010) by Ezer et al. Literature search was conducted in PubMed, Medline, EMBASE, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Main outcome measures were visual acuity, color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP). The JBI Critical Appraisal Checklists were used for quality assessment. Twelve studies were selected (out of 639 studies) for analysis of ethambutol optic neuropathy. Visual acuity improvement after stopping ethambutol was statistically significant. Similar improvement was not noted for other outcome measures. On comparing the results of this review with those by Ezer et al., significant improvement was noted in visual acuity, color vision, and visual field defects. Moreover, more patients reported increased optic nerve toxicity, color vision defects, and visual field defects in the present review. Hence, we conclude that the extended use of ethambutol beyond 2 months results in significant optic nerve toxicity. Further randomized controlled trials with different populations are needed to understand the magnitude of this issue.