Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity

Aims To evaluate incidence of toxic optic neuropathy in patients receiving ethambutol (EMB) for 6 months and to identify its early indicators. Methods We included 50 patients on anti-tubercular therapy (ATT) including EMB (HRE regimen) based on total body weight for 6 months. Best-corrected visual acuity (ETDRS), colour vision (Ishihara pseudo-isochromatic plates), contrast sensitivity (Pelli-Robson chart), Humphrey visual field analysis (HVF 30-2 SITA FAST), pattern visual evoked response (VER) and spectral-domain optical coherence tomography (SDOCT) for ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) analysis were assessed at baseline and at 2, 4 and 6 months after starting ATT. Results Mean age of the patients was 36.5 +/- 14.7 years with male:female ratio of 2.5:1. Mean daily dosage of EMB was 17.5 +/- 1.3 mg/kg/day. No significant change was observed in visual acuity, contrast sensitivity, color vision and mean or pattern SD on HVF at 6 months. Significant increase in VER latency of >2 SD (>125 ms) was observed in 46% eyes on follow-up indicating subclinical toxicity. Significant loss of mean RNFL (from 100.79 +/- 16.05 mu m to 89.96 +/- 13.79 mu m) and GCIPL thickness (from 83.1 +/- 5.60 mu m to 79.85 +/- 6.45 mu m) was observed at 6 months (p=0.001 for both). Patients with subclinical toxicity had significantly greater damage in temporal RNFL quadrant, supero-nasal and infero-nasal GCIPL sectors compared with others. Conclusion The incidence of clinical EMB optic neuropathy was <2%, though subclinical damage in the form of increase in VER latency, and decrease in RNFL and GCIPL on OCT was seen in 46% eyes.