Context Optic neuropathy is a well-known complication of ethambutol therapy and usually manifests as a decrease in visual acuity, cecocentral scotomas, and deficits in color vision. Objective To support or disprove the hypothesis that a significant majority of patients who develop ocular toxicity while undergoing treatment for a mycobacterium infection do so after experiencing either a prolonged course or unusually high serum levels of ethambutol. Design Retrospective chart review (16 cases) and literature meta-analysis (54 cases). Results Many cases lacked important data, but none countered the hypothesis. Age, duration of ethambutol, and dose of ethambutol were positively correlated with risk of toxicity. Conclusions Given an understanding of the risk factors for ethambutol optic toxicity, there exists a rationale for an optimization of ethambutol dosing protocols that can maximize the therapeutic effect while minimizing the incidence of optic toxicity.