Visual function test for early detection of ethambutol induced ocular toxicity at the subclinical level

Tuberculosis in developed countries is on the rise, and the main treatment ethambutol is known to induce ocular toxicity. However, to date, there are unknown tests or protocols for detecting subclinical ethambutol-induced ocular toxicity, which is important as early detection is related to symptom reversibility. We defined the ethambutol induced ocular toxicity as stastically siginificant change of visual function which was induced by ethambutol.

We aimed to identify a visual function test for the early detection of subclinical ethambutol-induced ocular toxicity. Furthermore, we also investigated the continuity or reversibility of early subclinical changes that were observed during the visual function tests after stopping ethambutol treatment.

The age range of 31 patients was from 13 to 72 years. The range of dosage was 15-19 mg/kg/day. The average period of dosage was 5 months. We performed a visual acuity test, visual field test, color vision test, contrast sensitivity test, fundus examination, retinal nerve fiver layer optical coherence tomography test (RNFL OCT) per month and pattern visual evoked potential test (pattern VEP) every 2 months before and during ethambutol treatment in 62 eyes of 31 patients. Among these patients, selected 21 patients were rexamined by these tests at the 3, 6 and 12 months after stopping ethambutol treatment. We compared the test results from the last follow-up during ethambutol treatment and after ethambutol stoppage with those obtained before ethambutol treatment (baseline).

RNFL OCT showed that average RNFL thickness increased 5 months after ethambutol treatment (p = 0.032), and pattern VEP showed that P100 latency was delayed in 2 and 4 months after ethambutol treatment (p = 0.001; p < 0.001, respectively). These early changes observed on RNFL OCT and pattern VEP progressed 6 months after ethambutol stoppage in 21 patients. Twelve months after ethambutol stoppage, these early changes returned to baseline levels. During the study, no changes in visual acuity, color vision, fundus, contrast sensitivity or visual field were observed.

Pattern VEP and RNFL OCT are suitable tests for the early detection of subclinical ethambutol-induced ocular toxicity. These tests should be performed until 12 months after ethambutol stoppage.