Ocular toxicity following ethambutol in standard dosage

doi:10.1016/0007-0971(86)90066-5

British Journal of Diseases of the Chest

Volume 80, 1986, Pages 288-291

https://doi.org/10.1016/0007-0971(86)90066-5 Get rights and content

Abstract

We describe a patient who developed rapid irreversible blindness following treatment with ethambutol in the recommended dose of 15 mg/kg body weight which in clinical practice is widely considered to be safe. This case exemplifies the potential risks of ethambutol and re-emphasizes the importance of instructing patients to stop the drug at once if they develop visual symptoms.

References (21)

G.J. Barron et al.
Ocular toxicity from ethambutol
Ann. J. Ophthalmol.
(1974)
A. Adel
Ophthalmological side effect of ethambutol
G. Boman et al.
A case of irreversible bilateral damage after ethambutol therapy
Scand. J. resp. Dis.
(1974)
British Thoracic and Tuberculosis Association
Short course chemotherapy in pulmonary tuberculosis
Lancet
(1976)
British Thoracic and Tuberculosis Association
Short course chemotherapy in pulmonary tuberculosis
R.E. Carr et al.
Ocular manifestations of ethambutol
Archs Ophthal.
(1962)
K.M. Citron
Ethambutol: a review with special reference to ocular toxicity
Tubercle
(1969)
N.J. Cooke
Editorial: treatment of tuberculosis
Br. med. J.
(1985)
W. Fox
Short course chemotherapy for tuberculosis
D.J. Girling
The hepatic toxicity of anti-tuberculous regimens containing isoniazid, rifampicin and pyrazinamide
Tubercle
(1978)

There are more references available in the full text version of this article.

Cited by (64)

Prospective evaluation of ethambutol toxic optic neuropathy in patients of pulmonary tuberculosis
2023, Indian Journal of Tuberculosis
The aim of the study was to evaluate visual parameters for early detection of ethambutol toxicity to prevent irreversible optic nerve damage.
This cohort study included 50 newly diagnosed cases of pulmonary tuberculosis, i.e. 100 eyes, in people aged 18–72 years, who received ethambutol as part of the antitubercular therapy. Before starting antitubercular treatment, at each monthly visit, ophthalmic examination was done that included best corrected visual acuity, optic disc evaluation, colour vision, contrast sensitivity, pupil cycle time and automated perimetry for a period of six months. Ethambutol was discontinued in patients who showed signs of visual impairment. These patients were observed for another three months for reversibility of toxicity.
Visual functions were normal in all patients at baseline. Out of 50 patients, 47 didn't show any signs of deterioration in visual functions even after six months of oral administration of ethambutol. However, 3 out of 50 patients, i.e. 6 eyes (6 %), showed signs of toxicity after 4–5 months – LogMAR visual acuity deteriorated from 0.00 to 1.08 (±0.40); mean contrast sensitivity deteriorated from 1.725 (±0.075) to 1.12 (±0.18); mean deviation in visual fields got impaired from −1.37 (±0.15) to −10.93 (±2.66); and colour vision got severely affected. All the affected patients were aged above 65.
In the present study, six percent of 50 patients showed ethambutol toxic optic neuropathy. It was concluded that patients should be comprehensively evaluated for visual parameters before starting the ethambutol treatment. They should be closely monitored by an ophthalmologist for visual functions every month to detect ethambutol toxicity at the early reversible stage to prevent irreversible damage to the optic nerve. Patients should be asked to report immediately if they detect any blurring of vision or colour vision abnormality.
Ocular side effects of drugs administered systemically for treatment of nonocular diseases
2022, Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics
Although the eye consists of barriers that isolated some of its structures from general blood circulation, this system is still vulnerable to side effects of drugs administered for the treatment of diseases affecting nonocular organs such as the cardiovascular and central nervous systems (CNS). The toxicities produced by drugs used for the treatment of nonocular diseases may have profound effect on ocular tissues such as the cornea, lens, and retina. Consequently, it is important for the clinical practitioner and students of the eye to be aware that their patients that are treated for nonocular diseases may be taking medications that could produce ocular side effects. These side effects could also be compounded by the fact that drugs that are administered for the treatment of eye diseases also have the potential to cause ocular side effects. Although the primary focus of this chapter is to summarize the ocular side effects of a wide variety of drug classes used for the treatment of nonocular diseases, we have also discussed the side effects of drugs used for the treatment of some ocular disorders.
Medical management of acute loss of vision in tuberculous meningitis: A case report
2020, Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
Citation Excerpt :
Optical coherence tomography (OCT) is a technology for measuring the retinal nerve fiber layer thickness that can detect early damage not visible by direct funduscopic examination [36]. Ethambutol ocular toxicity usually develops after several months of exposure but there are reports of severe visual impairment occurring as early as a few days after commencing treatment [37,38]. The incidence of ocular toxicity secondary to ethambutol appears to be dose-related [28,29] and predictors include poor renal function, which leads to failure to excrete the drug hence its accumulation, aging, prolonged duration of ethambutol use, a higher dose, hypertension, diabetes and concurrent optic neuritis related to tobacco and alcohol consumption [31].
Blindness and vision impairment are unpredictable complications of tuberculous meningitis (TBM) that are often unrecognized in the acute stages of illness due to inability to assess vision in patients with depressed levels of consciousness or confusion. We present a patient with definite TBM confirmed by positive Xpert MTB/RIF assay of cerebrospinal fluid (CSF) who developed binocular blindness two weeks after diagnosis and initiation of standard anti-tuberculosis treatment (ATT). Ophthalmological exam demonstrated complete bilateral abducens nerve palsies, impaired pupillary responses to light, normal optic discs, and visual acuity of hand motion only in each eye. Brain CT showed progressive enlargement of the third and lateral ventricles. We managed the patient medically with dexamethasone, acetazolamide, and substitution of moxifloxacin for ethambutol. Serial brain CTs confirmed gradual resolution of hydrocephalus. The patient had complete neurological recovery at six months except for residual blindness in the right eye. Visual acuity in the left eye recovered to normal (20/20). The assessment and management of vision impairment in TBM is discussed.
Ocular adverse events in drug sensitive TB patients on daily fixed dose combination anti-TB drugs: A record review study from Kerala, India
2020, Indian Journal of Tuberculosis
Citation Excerpt :
The non-availability of the status of Ocular ADE in 3 patients is still a limitation as it may be due to the non-resolution of the adverse event rather than lacunae in recording and reporting system. The recovery of non-resolving ocular ADEs may take several months26 and for capturing these delayed outcomes proper prolonged follow up monitoring systems has to be established. We also assessed whether the discontinuation of ethambutol had any adverse effect on the TB treatment outcome.
Government of India's Revised National TB Control Programme (RNTCP) has begun implementing daily fixed dose combination (FDC) anti-TB treatment regimen for drug sensitive TB patients in which ethambutol is given for six months. Prolonged ethambutol use is known to cause ocular adverse drug events (ADE).
To assess the magnitude of ocular ADEs in adult drug sensitive TB patients initiated on daily FDCs and to describe the demographic and clinical profile of patients with ocular ADEs.
We conducted a retrospective cohort study involving review of RNTCP records of all adult (age >14 years) drug sensitive TB patients initiated on daily FDCs between1^st January 2018 and 31st July 2018 in Thiruvananthapuram district, Kerala State, India.
714 patients were initiated on daily FDCs during the study period. It was unknown whether all patients had undergone assessment for ocular ADEs. However, of these 714 patients, 8 patients (1.1%) were documented to have had ocular ADEs. Seven of these 8 patients had received ethambutol more than 15 mg/kg body weight and had developed ocular symptoms (decreased/blurring of vision) 3 months after TB treatment initiation. Ethambutol was stopped in all these 8 patients. In 5 patients it was recorded that ocular ADEs had resolved following stoppage of ethambutol and in the remaining it was unknown.
The study confirms the occurrence of ocular ADEs among drug sensitive TB patients on daily FDCs and recommends strengthening of systems for assessing, documenting and managing ocular ADE.
Ethambutol-induced optic neuropathy in renal disorder: a clinico-electrophysiological study
2019, Canadian Journal of Ophthalmology
To report the spectrum of ethambutol induced optic neuropathy in a group of renal patients with tuberculosis and the role of visual evoked response (VER) in evaluating this disorder.
Twenty-three renal patients who were started on ethambutol as a part of anti-tubercular treatment for tuberculosis in India, were divided into 4 groups based on glomerular filtration rate (GFR): group 1—chronic kidney disease (CKD) with GFR < 10 mL/min; group 2—CKD with GFR 10-30 mL/min; group 3—GFR > 30 ≤ 60 mL/min; and group 4—GFR > 60 < 90 mL/min. Detailed clinical and electrophysiological (VER) examinations were carried out in all patients before starting the treatment with ethambutol and at a 3-month interval. Twenty healthy subjects formed the control group.
Ethambutol optic neuropathy developed in 6 (26%) patients with higher incidence (40%) in end-stage renal disease (group 1: CKD on dialysis). Vision was recovered in 4 cases on stoppage of ethambutol, whereas 2 patients (group 1: CKD on dialysis) developed bilateral severe irreversible visual loss and also had associated hepatic dysfunction. Three patients of ethambutol optic neuropathy showed increased latency in VER recording prior to visual loss and 1 patient showed demyelinating lesions in both optic nerves and optic radiation.
Ethambutol should be avoided in renal disorder patients in view of the high incidence of toxic optic neuropathy. Follow-up VER can detect sub-clinical ethambutol toxicity and would be useful for early diagnosis of optic neuropathy.
Rédiger un rapport sur l’éventail des neuropathies optiques à l’éthambutol chez des patients présentant à la fois une atteinte rénale et une tuberculose, d'une part, et sur le rôle des réponses évoquées visuelles (REV) dans l’évaluation de ce trouble, d'autre part.
Vingt-trois patients présentant une atteinte rénale qui avaient commencé à recevoir l’éthambutol dans le cadre d'un traitement antituberculeux en Inde ont été divisés en 4 groupes en fonction de leur débit de filtration glomérulaire (DFG): groupe 1 — néphropathie chronique (NC) et DFG < 10 mL/min; groupe 2 — NC et DFG 10-30 mL/min; groupe 3 — DFG > 30 ≤ 60 mL/min; et groupe 4 — DFG > 60 < 90 mL/min. Des examens cliniques et électrophysiologiques (REV) approfondis ont été réalisés chez tous les patients avant la mise en route du traitement par l’éthambutol et tous les 3 mois par la suite. Vingt sujets sains ont servi de témoins.
Une neuropathie optique à l’éthambutol est apparue chez 6 patients (26 %); l'incidence était plus élevée (40 %) en présence d'insuffisance rénale terminale (groupe 1: NC nécessitant une dialyse). La vision s'est rétablie chez 4 patients lorsque l'administration de l’éthambutol a été interrompue; par contre, 2 patients (groupe 1 : NC nécessitant une dialyse) ont présenté une perte de vision bilatérale grave et irréversible de même qu'une altération de la fonction hépatique. On avait noté une augmentation de la latence dans les enregistrements des REV avant l'apparition du déficit visuel chez 3 patients qui ont subi une neuropathie optique à l’éthambutol; de même, on a observé des lésions démyélinisantes des deux nerfs optiques et une atteinte des radiations optiques chez 1 patient.
Compte tenu de l'incidence élevée de neuropathie optique toxique, il convient d’éviter l'administration d’éthambutol en présence de néphropathie. Les REV de suivi peuvent mettre au jour une toxicité subclinique à l’éthambutol et pourraient être utiles dans le diagnostic précoce des neuropathies optiques.
Designing and testing single tablet for tuberculosis treatment through electrospinning
2016, Fabrication and Self-Assembly of Nanobiomaterials: Applications of Nanobiomaterials
Drug delivery systems refers to systems designed to transport or deliver drugs to treat a certain infected organ. Generally, these systems include loading of the drug and effective substances on a carrier (nanofibers, nanoparticles, nanorods, capsule, or matrix) and delivering these substances to the infected organs. The drugs can be used in the form of dispersion, emulsion, bandages, gels, creams, or as tablets. Developing controllable drug delivery systems allow them to be utilized in wide medical applications as wound dressings, skin treatments, or to treat internal infected organs. In this work, tuberculosis drugs (pyrazinamide, isoniazid, clarithromycin, and streptomycin) are loaded on poly(ε-caprolactone), poly(ethylene oxide), and poly(vinyl alcohol) nanofibers to design single tablets suitable for HIV patients. The activity of these drugs loaded on the nanofiber is tested against Mycobacterium avium through broth dilution assay and by agar plate assay. The minimal inhibitory concentration and the minimal bactericidal concentration are also studied.

View all citing articles on Scopus

^∗: Present address: 32 Wimpole Street, London W1.

View full text

General articleOcular toxicity following ethambutol in standard dosage

Abstract

Ann. J. Ophthalmol.

Ophthalmological side effect of ethambutol

A case of irreversible bilateral damage after ethambutol therapy

Scand. J. resp. Dis.

Short course chemotherapy in pulmonary tuberculosis

Lancet

Short course chemotherapy in pulmonary tuberculosis

Ocular manifestations of ethambutol

Archs Ophthal.

Ethambutol: a review with special reference to ocular toxicity

Tubercle

Editorial: treatment of tuberculosis

Br. med. J.

Short course chemotherapy for tuberculosis

The hepatic toxicity of anti-tuberculous regimens containing isoniazid, rifampicin and pyrazinamide

Tubercle

General article
Ocular toxicity following ethambutol in standard dosage