Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease.

Background: Ethambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.

Objectives: This study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.

Methods: We retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.

Results: Ethambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).

Conclusions: A lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.