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.

Automated summary

The study found that while the incidence of ethambutol-induced optic neuropathy was less than 2%, subclinical damage in the form of increased visual evoked response latency and decreased retinal nerve fiber layer and ganglion cell inner plexiform layer thickness on optical coherence tomography was observed in 46% of eyes.