Ethambutol, optic neuropathy

Color vision deficiencies are probably the most sensitive indicator of early ethambutol optic neuropathy and can occur even before visual acuity and visual fields are affected. Sometimes, contrast sensitivity can be affected before either visual acuity or color vision becomes impaired. 

Tsai RK, Lee YH. ReversibUity of ethambutol optic neuropathy. J Ocul PharmacolTher 1997 13 473-477. 

In another patient taking isoniazid and ethambutol, optic neuropathy improved only when both drugs were withdrawn (28). 

Epinephrine, see Adrenaline Erythromycin, versus the new macrohdes, 21.269 Erythropoietin, pure red cell aplasia, 27.348 status and safety, 16.400 Ethambutol, optic neuropathy, 30.358 Ethylene oxide, dialyser hypersensitivity,... 

Practitioners must be aware of the effects of systemic medications on vision and ocular health. Many drug-induced changes are common but benign, such as mild symptoms of dry eye associated with anticholinergic drugs. Some instances, however, can be vision threatening, such as ethambutol-induced optic neuropathy. Knowledge of systemic medications taken by individual... 

A review of certain chemicals is essential. Ethylene glycol is an antifreeze used for gasoline engines and may produce somnolence, imreactive pupils, disc swelling, and kidney failure. Systemic lead poisoning produces headaches, coma, cranial nerve palsies, and papilledema. Wood alcohol, or methanol, may produce severe toxic neuropathy and disc edema. Drugs known to produce toxic optic neuropathy include amiodarone (an antiar-rhythmic), quinine, aminoquinolines, ibuprofen, ethambutol, isoniazid, and chloramphenicol. 

The risk of optic neuropathy due to ethambutol may be increased when it is combined with isoniazid. 

Guerra R, Casu L. Hydroxycobalamin for ethambutol-induced optic neuropathy. Lancet 1981 2(8256) 1176. 

Karmon G, Savir H, Zevin D, Levi J. Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment. Ann Ophthalmol 1979 11(7) 1013-17. 

Jimenez-Lucho VE, del Busto R, Odel J. Isoniazid and ethambutol as a cause of optic neuropathy. Eur J Respir Dis 1987 71(l) 42-5. 

In addition to a normal eye, vision requires an intact circuit to and from the brain itself. The optic nerve (cranial nerve II), for example, carries retinal information to the occipital cortex in the posterior aspects of the brain. In addition, information concerning pupil size, direction of gaze, simultaneous movement of the eyes (conjugate gaze), and focus clarity is relayed from the brain back to the eye through multiple nerves. Ethambutol, an antituberculous medication, affects the optic nerves (optic neuropathy) whereas organic mercury compounds have been historically associated with toxic effects on the occipital cortex (cortical blindness). 

Ethambutol does not appear to affect serum isoniazid levels. However, it seems that the optic neuropathy caused by ethambutol may be increased by isoniazid. 

The mean serum levels of a 300-mg dose of isoniazid were not signifieant-ly ehanged in 10 patients with tubereulosis when they were given a single 20-mg/kg dose of ethambutol. The possible effeets ofeoneurrent use over a period of time were not studied. However, there is some evidence that the optic neuropathy caused by ethambutol may be increased by isoniazid, and any effects resolve more slowly after the use of isoniazid. One group of authors recommends that both ethambutol and isoniazid should be stopped immediately if severe optic neuritis occurs. They further recommend that isoniazid should be stopped if less severe optic neuritis does not improve within 6 weeks after stopping ethambutol. ... 

Nervous system The adverse effects of antituberculosis drugs on the nervous system have been reviewed [1 ]. Isoniazid is most often associated with nervous system reactions, most prominently peripheral neuropathy, psychosis, and seizures. Optic neuropathy can occur with ethambutol and ototoxicity and neuromuscular blockade with aminoglycosides. Cycloserine can cause psychosis and seizures, and the psychosis in particular limits its use. Fluoroquinolones are rare causes of seizures and delirium. Significant neurotoxicity has not been documented with newer forms of therapy under development. 

Autosomal dominant optic atrophy is an inherited optic neuropathy with variable penetrance and expressivity. Other genetic and environmental factors are postulated to contribute to more marked visual loss in some affected individuals. In an atypical case of ethambutol toxicity, with progressive profound loss of vision despite drug withdrawal, a diagnosis of autosomal dominant optic atrophy was made when the proband s sons presented with mild visual disturbances and color vision defects, confirmed by electrophysiology and OPAl gene mutational analysis [13 ]. 

Reduced visual acuity and central or centro-cecal scotomas on visual field testing have been reported as the usual presentation of eth-ambutol-induced optic neuropathy. Bilateral temporal hemianopia has been reported in a case of ethambutol toxicity [64 ]. 

The mechanism of ethambutol-induced optic neuropathy is unclear. It has been postulated that it is caused by a disturbance in mitochondrial metabolism. Ethambutol is also a strong chelator of copper, a co-factor of cytochrome c oxidase, which is required for axonal transport in the optic nerves, failure of which, secondary to mitochondrial insufficiency, results in optic neuropathy. Ethambutol is specifically toxic to retinal... 

In a retrospective study of 857 Korean patients who took ethambutol, 89 had impaired vision [65 ]. Ethambutol-induced optic neuropathy was diagnosed in during a mean follow-up period of 13 months. The average dose of ethambutol was 18 mg/kg/ day and the duration of therapy was 9.4 months. Ophthalmic findings included reduced visual acuity (n = 58), abnormal visual fields (n = 58), abnormal color vision (55), optic disc pallor (34), and increased latency on VEP tests (58). Slightly less than one-third of the patients had improved visual function after discontinuing ethambutol. The mean time to recovery was 5.4 months. However, no patient with optic disc pallor at the time of diagnosis had improved visual function. Renal dysfunction and the daily dose of ethambutol, but not the duration of treatment, contributed. The authors estimated the incidence of ethambutol-induced optic neuropathy in Koreans to be under 2%. Thus, visual function after withdrawal of ethambutol is reversible in only a minority of patients and does not occur if optic disc pallor is present. 

Chen HY, Lai SW, Muo CH, Chen PC, Wang IJ. Ethambutol-induced optic neuropathy a nationwide population-based study from Taiwan. Br J Ophthalmol 2012 96(11) 1368-71. 

A. Ethambutol is associated with retrobulbar neuritis, resulting in loss of central vision and impaired red-green discrimination. Ethionamide (B) is an analogue of isonicotinic acid and is associated with GI intolerance and peripheral neuropathy, but not the optic neuritis or color vision discrimination problems. Aminosalicylic acid (C) can cause GI irritation and bleeding problems, so caution is required in peptic ulcer patients. It has no neurological side effects. Rifampin (D) is associated with red-orange discoloration of saliva, tears, and urine but not the color vision problems. Isoniazid (E) is associated with peripheral neuritis in chronic alcoholics and malnourished individuals and requires pyridoxine supplements. It is not associated with optic neuritis. 

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxic-ity, peripheral neuropathy, optic neuritis, and Gl side effects. All four agents can potentially be hepatotoxic, but this side effect is most frequently associated with isoniazid and rifampin. Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators include people of Asian or American Indian descent and are less predisposed to these adverse effects. 

Ethambutol >15mg/kg/day Optic neuritis, red/green colorblindness, peripheral neuropathy. 

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