Hobson’s choice – fixed drug combinations for tuberculosis and epidemic of ethambutol-induced optic neuropathy in India

Dear Editor, I read with interest the article, “Ethambutol optic neuropathy in extended anti-tubercular therapy regime: A systematic review.”[1] Loss of vision due to ethambutol has reached epidemic proportions as the patients are not warned about the visual side effects to look out for by their treating physicians. They come scurrying late to us with profound visual loss, which is only partially reversible. It is a Hobson’s choice between Scylla, which is a six-headed monster like tuberculosis (the master mimicker), and Charybdis, which is the whirlpool of vision loss due to ethambutol optic neuropathy (EON). Hence, before starting antitubercular therapy, all candidates should undergo a complete ophthalmic exam and a periodical exam during the complete treatment course. The adage “prevention is better than cure” was never truer for EON (with additional threat of linezolid – a second line therapy – too causing optic neuropathy). In our tertiary care institution, the incidence of EON has increased exponentially since the fixed drug combination (FDC) of first line of antituberculosis drugs in the Revised National Tuberculosis Control Program (RNTCP) that used the directly observed short course chemotherapy (DOTS) protocol. This regimen involves taking ethambutol daily in a higher dose for the entire 6 months, leading to EON, which is dose dependent. The World Health Organization (WHO)-suggested dosage was 15–20 mg/kg/day to start with and reduced it to 15 mg/kg/day. But as per FDC in India, the dosage is higher in all age groups. The onset of EON starts with bilateral diminished vision at approximately 3 months of therapy, along with color vision getting affected.[2] The adage commonly used for retrobulbar neuritis, “patient can’t see anything outside, and the doctor doesn’t see anything wrong inside,” holds true in these cases (late-stage EON leads to optic atrophy). Visual field defect observed is a central scotoma, with magnetic resonance imaging (MRI) brain showing T2-hyperintense signals in the optic nerves in advanced cases. The treatment for the condition is stoppage of ethambutol immediately and starting the patient on zinc and copper supplements with vitamin B complex for 3–6 months. The etiology of EON is inhibition of lysosomal activation due to zinc chelation and disrupted oxidative phosphorylation secondary to copper depletion in the mitochondria. A subset of patients with profound visual loss was started on a course of oral steroids. On average, a two-line Snellen improvement is seen in less than 50% of cases. Patients with disc pallor, visual field scotomas and optical coherence tomography (OCT) and visual evoked potential (VEP) changes had poor visual outcomes. The chest physicians and DOTS center doctors should actively look out for EON if any patient has visual symptoms and immediately stop ethambutol. In our country, lack of awareness leads to irreversible blindness with major socioeconomic consequence, as these patients are young and in the productive years of their lives. The best way to sensitize the chest physicians and patients to the risks of visual impairment with prolonged ethambutol (EMB) regimen (at a higher dose) is to screen the patients in the chest outpatient department (OPD) itself using Ishihara color vision chart and Amsler grid and refer them to an ophthalmologist at the earliest signs of visual impairment. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.