Incidence of ethambutol-related visual impairment during treatment of active tuberculosis
ABSTRACT BACKGROUND: Recent World Health Organization guidelines recommend the addition of ethambutol (EMB) throughout standardised treatment of new cases of active tuberculosis (TB) in populations with increased prevalence of isoniazid resistance to reduce the risk of creating multidrug resistance. This could expose patients to the risk of blindness.METHODS: We searched Cochrane, Embase and PubMed electronic databases from 1965 to February 2011 for original studies that prospectively followed all patients treated with EMB for active TB, and routinely ascertained the occurrence of visual toxicity using standard methods. Pooled estimates, overall and stratified by major covariates, were calculated using random effects meta-analysis.RESULTS: Pooled cumulative incidence of any visual impairment in all patients was 22.5 per 1000 persons treated with EMB (95%CI 10.2-35), and permanent impairment was 4.3/1000 (95%CI 0.3-9.0). After restricting the analyses to arms in which the average dose was 27.5 mg/kg/day or less and treatment was for 2ndash;9 months, the incidence of any visual impairment was 19.2/1000 (95%CI 5.8-33), and permanent impairment was 2.3/1000 persons (95%CI 0-6.1) treated, as the majority of episodes were reversible. In reversible cases, resolution of impairment occurred after an average of 3 months.CONCLUSIONS: In this review, any visual impairment occurred in 22.5/1000 persons receiving EMB at standard doses for up to 9 months, and permanent impairment in 2.3/1000-an important risk. However, these estimates are imprecise, and the studies were of variable quality and the results heterogeneous. Well-designed prospective studies with repeated measurements of multiple visual parameters that clearly describe the degree of permanent impairment are needed.
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ABSTRACT: There is a growing need to identify appropriate standardized treatment strategies that will adequately treat various forms of drug-resistant TB and prevent multidrug-resistant TB.A Markov model estimated treatment-related acquired MDR-TB, mortality, disability-adjusted life years, and costs in settings with different prevalence of mono-INH resistant and MDR-TB. We compared four treatment strategies: 1) standard WHO-recommended treatment strategy; 2) adding EMB throughout the 6-month treatment of new cases; 3) using a strengthened standardized retreatment regimen; and 4) using standardized MDR treatment for failures of initial treatment. Treatment-related outcomes were derived from published literature, and costs from direct surveys.A strengthened retreatment regimen, which could achieve lower failure, relapse and acquired MDR rates in mono-INH-resistant cases, was predicted to be the most cost-effective strategy in all four settings. Empiric MDR treatment of failures of initial treatment was the most costly strategy but resulted in the fewest deaths. Adding EMB throughout initial treatment would be most effective in preventing acquired MDR, but would lead to excess cases of blindness.A high priority should be given to improving the standardized retreatment regimen, as this is predicted to produce greater benefits than other recently recommended strategies.European Respiratory Journal 06/2013; 43(2). DOI:10.1183/09031936.00005613 · 7.64 Impact Factor
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ABSTRACT: To determine whether HIV and the use of antiretroviral therapy is a risk factor for the development of ethambutol toxic optic neuropathy. To describe the clinical course of ethambutol toxic optic neuropathy in patients with HIV and to identify prognostic factors. The case notes of 14 consecutive patients referred to the neuro-ophthalmology clinic were reviewed. Data regarding HIV status, antiretroviral therapy, visual function, ethambutol therapy dosage, and ethambutol therapy duration were collected and analysed. Eleven of the 14 patients were HIV positive. Ten of the HIV positive patients were receiving antiretroviral therapy. The mean dose of ethambutol was 17.25mg/kg/day. No statistically significant difference in mean dose, duration of therapy, age or CD4 count was found between those who showed visual improvement and those who did not. Delay in presentation of more than one month post symptom onset was correlated with poor visual outcome (P=0.001). HIV and, perhaps more importantly, the potential mitochondrial toxic effects of Nucleoside analogue reverse transcriptase inhibitors (NRTIs) may be a risk factor for the development of toxic optic neuropathy from ethambutol therapy via a multiple hit effect. Delay in presentation results in poor visual outcome. Regular monitoring is recommended for HIV positive patients receiving antiretrovirals and requiring ethambutol therapy in order to avoid permanent visual loss.International Journal of Ophthalmology 08/2013; 6(4):542-5. DOI:10.3980/j.issn.2222-3959.2013.04.25 · 0.71 Impact Factor
Article: Inflammatory Optic Neuropathies[Show abstract] [Hide abstract]
ABSTRACT: Purpose of review: The aim of this review is to highlight the clinical presentation of a variety of inflammatory optic neuropathies through a case-based format. While emphasis will be placed on optic neuritis, which represents the most common acquired inflammatory optic nerve injury, the cardinal clinical features of other demyelinating forms of optic neuropathy and potential mimics for typical optic neuritis will be discussed. Recent findings: Novel developments in the diagnostic evaluation, clinical associations, and treatment options for several inflammatory optic neuropathies will be described. Key points will emphasize clinical pearls and potential pitfalls that may thwart early diagnosis of underlying demyelinating, infectious, and inflammatory diseases presenting with optic nerve involvement. Summary: This review will aid the clinician in identifying potential red flags that should prompt consideration for causes of inflammatory optic nerve injury linked to neurologic and systemic disorders, and help guide safe and effective management for these conditions.CONTINUUM Lifelong Learning in Neurology 08/2014; 20(4 Neuro-ophthalmology):816-37. DOI:10.1212/01.CON.0000453316.60013.52