Recovery after severe ethambutol intoxication - psychophysical and electrophysiological correlations

Abstract

Six patients with severe ocular side effects caused by therapeutical doses of the tuberculostatic drug ethambutol were investigated during the course of recovery with psychophysical and electrophysiological methods. Three patients developed an optic atrophy with permanently reduced vision as a likely consequence of additional risk factors such as diabetes, alcohol abuse, and reduced kidney function. The severity of the neuritis of the optic nerve was not related to the total intake of ethambutol. The likelihood of a permanent ocular damage increased sharply if the visual acuity had dropped below a value of 1/10. permanently prolonged latency of the P-100 component was found in visual evoked potentials even in cases with good recovery from ethambutol-induced damage. The recovery of color vision could be monitored very well with the Farnsworth-Munsell 100-Hue Test which revealed a diffuse impairment of color discrimination with a slight prevalence of the red-green axis. In addition to the known disturbances of the red-green antagonistic neurons, it could be demonstrated by measuring transient tritanopia and spectral sensitivity functions that ethambutol also affects the blue-yellow antagonism at the retinal level.

Retinal Function and Morphology in Monkeys with Ethambutol-Induced Optic Neuropathy

“…1,2 Abnormal visual evoked potentials (VEPs) with normal electroretinograms (ERGs), indicating involvement of the optic nerve and/or the more proximal visual pathway, has been reported in ethambutol-treated patients. 3,4 In animal experiments, ethambutol-induced histopathologic lesions, mainly consisting of demyelination in the visual pathway (extending from the optic nerve to the optic tract), have been reported in many species, [5][6][7][8] suggesting that similar morphological changes occur in patients. Therefore, the aforementioned visual disturbances in ethambutol-treated patients are generally associated with retrobulbar optic neuritis (i.e., optic neuropathy).…”

“…An alternate explanation is that, as a result of the serial ERG recording, we detected a relatively early change in the retina, and the functional changes in the macular area had not occurred yet. VEP 3,4,29,34,35 and OCT 26,27,[36][37][38] have been reported to be objective tools to detect optic neuropathy induced by ethambutol. By means of serial recordings of the PhNR in the present study, we have found that the function of RGCs was gradually and severely affected in two out of three monkeys receiving repeated doses of ethambutol.…”

Natural Course and Prognostic Factors of Ethambutol Toxic Optic Neuropathy

“…In a previous study, although the visual acuity improved in some patients, other visual functions, including color vision, visual eld, and electrophysiology, showed dysfunctions. 9 The occurrence of ETON depends on the dosage of EMB 10,11 and can also be induced by a relatively low dosage (10 mg/kg/day). We could not analyze the effects of dosage of EMB because the number of patients whose medical records had detailed information on the dosage was too small to draw meaningful results.…”

Multifocal electroretinography changes in patients on ethambutol therapy

“…5 In additiona to optic nerve toxicity, studies have also showed that ethambutol might also be toxic at the level of the retina. [6][7][8][9] Multifocal electroretinography (mfERG) is an investigational tool, which allows the stimulation and recording of localized retinal responses from the macula topographically. 10,11 Case reports have shown that mfERG can be used to detect the retinal functional abnormalities in patients with visual loss associated with ethambutol therapy.…”