Neuro-ophthalmic complications of tuberculosis and its treatment: a systematic review and meta-analysis

Tuberculosis (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.

Following 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.

Twenty-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.

TB-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.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251141453.