Background: Graves' ophthalmopathy (GO) is a common cause of morbidity in patients with Graves' disease. Optimal treatment of GO remains unclear, and evidence-based approach may improve patients outcome.

Methods: A systematic review and meta-analysis of randomized, controlled trials comparing treatment modalities for GO versus placebo, no intervention, or other treatments. Primary outcome was the clinical activity score (CAS).

Results: Thirty three trials evaluating 1,367 patients, fulfilled inclusion criteria. In patients with moderate to severe GO, intravenous pulse corticosteroids were significantly better than oral corticosteroids in reducing CAS (standardized mean difference -0.64, 95% CI -1.11 to -0.17, Chi²=7.91, I²=62%, random effect), with lower rate of adverse events. Somatostatin analogs showed a minor but statistically significant advantage over placebo (mean difference -0.63, 95% CI -0.98 to -0.28). There was no advantage of orbital radiotherapy over sham radiation in CAS, but radiotherapy was superior for response rates of diplopia (odds ratio 4.88, 95% CI 1.93 to 12.34, 2 trials). Treatment with combination of orbital radiotherapy and corticosteroids was significantly better than with either treatment alone (standardized mean difference -1.05, 95% CI -1.62 to -0.48).

Conclusions: Current evidence demonstrates the efficacy of intravenous corticosteroids in decreasing CAS in patients with moderate-to-severe GO. Intravenous pulse corticosteroids therapy has a small but statistically significant advantage oral therapy, and causes significantly less adverse events. Somatostatin analogs have marginal clinical efficacy. The efficacy of orbital radiotherapy as single therapy remains unclear, while the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral costicosteroids alone.