Abstract
PURPOSE: To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED). METHODS: A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including in vitro) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of H(2)O(2)-dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the in vitro studies. RESULTS: Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 in vitro studies from 1993 to 2018. While β-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in in vitro studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial. CONCLUSION: While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice.