Ethambutol visual impairment

UNTOWARD EEEECTS The most important side effect is optic neuritis, resulting in decreased visual acuity and red-green color blindness. The incidence of this reaction is proportional to the dose of ethambutol and is <1% in patients receiving the recommended daily dose of 15 mg/kg. The intensity of the visual difficulty is related to the duration of therapy after visual impairment first becomes apparent and may be unilateral or bilateral. Tests of visual acuity and red-green discrimination prior to the start of therapy and periodically thereafter are recommended. Recovery usually occurs when ethambutol is withdrawn. 

Ezer N, Benedetti A, Darvish-Zargar M, Menzies D. Incidence of ethambutol-related visual impairment during treatment of active tuberculosis. Int J Tuberc Lung Dis 2013 17(4) 447-55. 

The major toxicity associated with ethambutol use is retrobulbar neuritis impairing visual acuity and red-green color discrimination this side effect is dose related and reverses slowly once the drug is discontinued. Mild GI intolerance, allergic reaction, fever, dizziness, and mental confusion are also possible. Hyperuricemia is associated with ethambutol use due to a decreased renal excretion of urates gouty arthritis may result. 

For instance, blurring of vision and diplopia are caused by the use of imipramine, iproniazid, chlorpromazine, thioridazine, and promethazine. Impairment of visual acuity is caused by chlorpropamide, tolbutamide, alcohol, chlorpromazine, phenylbutazone, indomethacin, chloroquine, sulfonamides, ethambutol, chloramphenicol, isonex, clioquinol, quinine, streptomycin, and paraaminosalicylate. Yellow vision (xanthopsia) has been traced to the use of sulfonamides, streptomycin, methaqualone, barbiturates, chlorothiazide,... 

Retrobulbar neuritis is the major adverse effect noted in patients treated with ethambutol, Patients usually complain of a change in visual acuity and/or inability to see the color green. Vision testing should be performed on all patients who must receive ethambutol for more than 2 months. Impairment of eighth cranial nerve function is the most important adverse effect of streptomycin, Vestibular function is most frequently affected, but hearing may also be impaired. Audiometric testing should be performed in patients who must receive streptomycin for more than 2 months. Streptomycin occasionally causes nephrotoxicity. 

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. 

THERAPEUTIC USES Ethambutol (myambutol) has been used with notable success in the therapy of tuberculosis when given concurrently with isoniazid and largely has replaced aminosalicylic acid. Ethambutol is available for oral administration in tablets. The usual adult dose is 15 mg/kg given once a day. Some clinicians use 25 mg/kg/day for the first 60 days, followed by 15 mg/kg/day, particularly for those treated previously. Dose adjustment is necessary in patients with impaired renal function. Ethambutol is not recommended for children under 5 years of age because of concern about the ability to test their visual acuity. Children from ages 6-12 years should receive 10-15 mg/kg/day. 

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. 

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