Ethambutol-Induced Ocular Toxicity and Optic Neuropathy

Ethambutol, a cornerstone agent in antitubercular therapy, is associated with dose- and duration-dependent ocular toxicity, most notably optic neuropathy. This adverse effect manifests as painless, bilateral visual decline, dyschromatopsia and visual field defects, often sparing central visual acuity in its early stages. Pathologically, there is selective injury to retinal ganglion cells and their axons, with subsequent thinning of the peripapillary retinal nerve fibre layer (RNFL) and ganglion cell layer detectable by optical coherence tomography (OCT). Impaired mitochondrial function, dysregulated autophagy and oxidative stress have all been implicated in the mechanistic cascade leading to ganglion cell apoptosis. The global burden of tuberculosis renders this complication of broad public health importance, prompting ongoing efforts to refine risk stratification, monitoring protocols and early detection methods. Prompt cessation of ethambutol typically allows partial or full visual recovery in most patients, but permanent deficits occur in a minority, underscoring the need for vigilant screening and collaboration between respiratory and ophthalmic services.

Research from Nature Portfolio

Recent work has explored objective functional biomarkers of toxicity. A study employing digital pupillometry demonstrated that patients with ethambutol-induced optic neuropathy exhibit significantly reduced pupillary constriction ratio and slower constriction and dilation velocities compared with both ethambutol-treated controls without neuropathy and healthy individuals. These pupillary light reflex parameters correlated strongly with macular ganglion cell layer thickness, suggesting that non-invasive pupillometry could serve as a rapid, quantitative adjunct to structural imaging in the early identification and monitoring of ethambutol-induced optic nerve injury.

Ethambutol-Induced Ocular Toxicity and Optic Neuropathy publication trend

The graph below shows the total number of articles in ethambutol-induced ocular toxicity and optic neuropathy across all publications each year (not limited to Nature Index journals).

Technical terms

Optic neuropathy: Injury or dysfunction of the optic nerve leading to impaired signal transmission from the retina to the brain.

Retinal nerve fibre layer (RNFL): Layer of unmyelinated axons of retinal ganglion cells; its thickness reflects axonal integrity and can be measured by OCT.

Optical coherence tomography (OCT): Non-invasive imaging technique that produces high-resolution cross-sectional images of retinal structures.

Pupillometry: Quantitative measurement of pupillary light reflex parameters—such as constriction latency and velocity—often used to assess autonomic and optic nerve function.

References

1. Risk Factors of Optic Neuropathy in Ethambutol Users: Interaction with Isoniazid and Other Associated Conditions of Toxic Optic Neuropathy. Toxics (2024).
2. Ethambutol induces impaired autophagic flux and apoptosis in the rat retina. Disease Models & Mechanisms (2015).
3. The use of optical coherence tomography for the detection of ocular toxicity by ethambutol. PLOS ONE (2018).
4. Analysis of structural injury patterns in peripapillary retinal nerve fibre layer and retinal ganglion cell layer in ethambutol-induced optic neuropathy. BMC Ophthalmology (2021).
5. Pupillary light reflex in ethambutol-induced optic neuropathy. Scientific Reports (2020).