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 The latter was eventually withdrawn from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
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.