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Treatment Modalities for Graves’ Ophthalmopathy: Systematic Review and Metaanalysis

Neuroophthalmology Unit (H.S.-K.), Departments of Medicine E (E.R., L.L.) and Ophthalmology (H.S.-K., M.H., D.E.), and Institute of Endocrinology and Metabolism (E.R., I.S.), Rabin Medical Center, Petah Tikva 49100, Israel; and Sackler School of Medicine (H.S.-K., E.R., D.E., I.S., L.L.), Tel Aviv University, Tel Aviv 69978, Israel

Address all correspondence and requests for reprints to: Hadas Stiebel-Kalish, M.D., Chief, Neuro-Ophthalmology Unit, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel. E-mail: kalishhadas{at}gmail.com.

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

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

Results: Thirty-three trials evaluating 1367 patients fulfilled inclusion criteria. In patients with moderate to severe GO, iv pulse corticosteroids were significantly better than oral corticosteroids in reducing CAS [standardized mean difference –0.64, 95% confidence interval (CI) –1.11 to –0.17, ² 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 1.93–12.34, two 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 iv 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 fewer adverse events. Somatostatin analogs have marginal clinical efficacy. The efficacy of orbital radiotherapy as single therapy remains unclear, whereas the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral corticosteroids alone.