Histopathology of experimental ethambutol intoxication

Ethambutol {the dextro isomer of 2,2'-(ethylenediimino)di-l-butanol) is widely used for the treatment of pulmonary tuberculosis. Like all drugs it may produce undesirable side effects, the most notable being amblyopia. Instances of impaired vision were recognized shortly after the racemic form of the drug was introduced, but detailed case histories were not published until Carr and Henkind described toxic amblyopia in a man treated with the drug. Subsequently it was shown that although most of the therapeutic effect resided in the dextro isomer, the levo isomer possessed most of the toxicity. As a result ethambutol is now used only in the dextro form. Despite that, and limitation of dosage, cases of visual impairment due to ethambutol continue to be reported. In the only histopathological study of the brain and eye of such a patient there was demyelination in the optic chiasm. Studies of ethambutol intoxication in animals have also shown that lesions may occur in the optic chiasm.' ° Stimulated by these observations, I investigated the effect of ethambutol intoxication in the anterior visual system of the albino rat.