Background

Ethambutol Hydrochloride (EMB), first introduced in 1961, remains an important first-line drug in the treatment of tuberculosis. Its original formulation was a racemic mixture, with the D-isomer providing most of the therapeutic effect and the L-isomer providing much of the toxic effect. The latter was eventually withdrawn from the market so that EMB is now only available in the D-form3. Since the very first published report on ethambutol-related ocular toxicity came out in 19624, EMB is now the most widely implicated drug causing toxic optic neuropathy in man.

The main culprit behind EMB’s toxicity appears to be its chelating property, as it may alter the Cytochrome-C Oxidase activity and mitochondrial metabolism in optic nerves5. Studies have shown an association with decreased serum zinc and copper levels6-7. There is also evidence in the literature showing that ocular toxicity is dose and duration-dependent8-13. Renal disease is an important risk factor for the development of ocular toxicity14. Barron et al., in a 1974 report, declared that 25mg/kg/day (locally-available commercial preparations contain less dosage) for 60 days followed by 15mg/kg/day for an indefinite period is exceedingly safe15. However, toxicity has been reported to occur even at safe doses16-17. Some authors believe that in the elderly, there is no such thing as a "safe dose"18.

There are two main types of ETON10. The Central Type is a non-inflammatory type of optic neuropathy (perhaps inappropriately called "optic neuritis" in older literature) that affects the central/axial fibers of the optic nerves. Patients present with deficits in visual acuity, color perception (red-green mostly), and visual fields (central/ceco-central scotoma). Most patients with ETON present with this type of toxicity. The less common Peri-axial Type affects the peripheral fibers of the optic nerves and can lead to visual field constriction. Especially in the early stages, the patient can present with normal visual acuity and color perception. This underscores the precaution that 20/20 visual acuity DOES NOT rule out ETON.