What is the association between Ethambutol (Ethambutol hydrochloride) and optic neuropathy leading to vision loss?

From the Guidelines

Ethambutol can cause vision loss through optic neuritis, and it is essential to monitor patients for this side effect, particularly those with prolonged use or higher doses, as vision changes are usually reversible if the medication is promptly discontinued. This side effect occurs in approximately 0.5% of patients taking standard doses, as reported in a recent review of the tolerability of TB drugs 1. The risk of developing ethambutol-related ocular toxicity is greater with longer treatment durations, and patients should be instructed to immediately report any visual changes, including blurred vision, decreased acuity, or color perception changes.

Key Considerations

• Ethambutol's chelation of zinc and copper disrupts mitochondrial function in retinal ganglion cells, causing axonal damage to the optic nerve.
• Renal impairment increases the risk of vision loss due to decreased drug clearance, so dosage adjustment is necessary in patients with kidney disease.
• Vision typically improves within weeks to months after discontinuation, though complete recovery may take up to a year in some cases.
• Baseline visual acuity and color discrimination testing should be performed before beginning treatment, with monthly monitoring during therapy.

Monitoring and Prevention

• Patients should be closely monitored for signs of optic neuritis, including decreased visual acuity, scotomata, color blindness, or visual defects.
• The risk of ethambutol-related ocular toxicity is greater with daily therapy compared to intermittent therapy, as reported in a retrospective analysis 1.
• Patients with prolonged use or higher doses should be closely monitored, and dosage adjustment should be considered to minimize the risk of vision loss.

From the FDA Drug Label

ADVERSE REACTIONS ETHAMBUTOL HCl may produce decreases in visual acuity, including irreversible blindness, which appear to be due to optic neuritis. Optic neuropathy including optic neuritis or retrobulbar neuritis occurring in association with ethambutol therapy may be characterized by one or more of the following events: decreased visual acuity, scotoma, color blindness, and/or visual defect WARNINGS ETHAMBUTOL HCl may produce decreases in visual acuity which appear to be due to optic neuritis. This effect may be related to dose and duration of treatment. This effect is generally reversible when administration of the drug is discontinued promptly. However, irreversible blindness has been reported.

Ethambutol and Vision Loss: Ethambutol may cause decreases in visual acuity, including irreversible blindness, due to optic neuritis.

• Key Points:
  • Decreases in visual acuity may be unilateral or bilateral.
  • Patients should be advised to report promptly to their physician any change of visual acuity.
  • Testing of visual acuity should be performed before beginning ETHAMBUTOL HCl therapy and periodically during drug administration.
  • Irreversible blindness has been reported, although the effect is generally reversible when administration of the drug is discontinued promptly 2 2.

From the Research

Ethambutol and Vision Loss

• Ethambutol, a first-line chemotherapeutic agent used in combination with other drugs for the treatment of tuberculosis, has been associated with optic neuritis and vision loss 3, 4, 5, 6, 7.
• The risk of optic neuropathy increases with the extended use of ethambutol beyond 2 months 5.
• Studies have reported cases of serious visual impairment due to ethambutol therapy, with some patients experiencing permanent vision loss 3, 4, 6.
• Visual acuity improvement after stopping ethambutol has been statistically significant, but similar improvement may not be noted for other outcome measures such as color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP) 5.
• Factors such as diabetes mellitus, glaucoma, and heavy smoking may contribute to irreversible visual impairment in patients taking ethambutol 7.

Recommendations and Precautions

• The usual daily dose of ethambutol should be 15 mg/kg/day, and regular formal ophthalmological evaluation is recommended for patients with comprehension or communication difficulties 3.
• Ethambutol and isoniazid should be stopped immediately if severe optic neuritis occurs, and isoniazid should be stopped if less severe optic neuritis does not improve within six weeks after stopping ethambutol 3.
• Early recognition of optic neuropathy and prompt discontinuation of the drug are crucial in preventing permanent vision loss 7.
• Alternative antituberculous agents should be considered due to the potential for serious visual impairment associated with ethambutol 6.