Ethambutol optic neuropathy incidence 1.54 percent with renal impairment and hypertension as key risk factors
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Key Takeaway
Consider screening high-risk patients for ethambutol optic neuropathy given the 1.54 percent incidence and identified risk factors.
This is a systematic review and meta-analysis examining the incidence and risk factors of ethambutol optic neuropathy (EON), neuro-ophthalmic manifestations of tuberculous meningitis (TBM), and prognostic biomarkers for visual outcomes. The analysis included a total sample size of 260,430. The pooled incidence of EON was 1.54 percent (95% CI: 0.81-2.49 percent, I²=98.2 percent). Renal impairment was associated with an increased risk of EON (OR 3.73, 95% CI: 1.78-7.83), as was hypertension (OR 2.37, 95% CI: 1.46-3.84). In TBM, cranial nerve III palsy occurred in 17.4 percent of cases, papilledema in 12.5 percent, and optic atrophy in 16.7 percent. Hydrocephalus rates were higher in pediatric patients (72.5 percent) versus non-pediatric patients (13.0 percent), with a relative risk of 5.56. For subclinical changes, VEP demonstrated better detection than OCT (Hedges’ g difference: 0.686, P-value = 0.001). Visual recovery in clinical EON cases was 52.4 percent, with younger age and earlier ethambutol discontinuation associated with improved recovery. The authors note the high heterogeneity (I²=98.2 percent) as a limitation. Screening protocols targeting high-risk populations are recommended.
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View Original Abstract ↓
IntroductionTuberculosis (TB) and its treatment have been associated with significant neuro-ophthalmic morbidity; however, the magnitude and determinants of these complications remain incompletely characterized. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of ethambutol optic neuropathy (EON), neuro-ophthalmic manifestations of tuberculous meningitis (TBM), and prognostic biomarkers for visual outcomes.MethodsFollowing PRISMA 2020 guidelines, we searched PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar up to the 30th of September 2025. Studies reporting EON incidence, TBM neuro-ophthalmic complications, or subclinical neurotoxicity biomarkers were included. Random-effects meta-analysis with generalized linear mixed models was performed.ResultsTwenty-two studies (N = 260,430) were included. Pooled EON incidence was 1.54% (95% CI: 0.81-2.49%, I²=98.2%). Renal impairment (OR 3.73, 95% CI: 1.78-7.83) and hypertension (OR 2.37, 95% CI: 1.46-3.84) were significant risk factors. TBM neuro-ophthalmic manifestations included cranial nerve III palsy (17.4%), papilledema (12.5%), and optic atrophy (16.7%), with pediatric patients demonstrated significantly higher hydrocephalus rates (72.5% vs 13.0%, RR 5.56). Visual evoked potential (VEP) demonstrated better detection of subclinical changes over optical coherence tomography (OCT) (Hedges’ g difference: 0.686, P-value = 0.001). Visual recovery occurred in 52.4% of clinical EON cases. Factors associated with improved recovery included younger age (MD= -3.8 years, P-value= 0.095) and earlier ethambutol discontinuation.ConclusionsTB-related neuro-ophthalmic complications represent significant morbidity with identifiable risk factors. Visual evoked potentials offer superior subclinical detection and early intervention improves visual outcomes. Screening protocols targeting high-risk populations are recommended.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251141453.
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