Graves' ophthalmopathy is defined as autoimmune inflammation of extraocular 
muscles and orbital fat or connective tissue, usually in patients with Graves' 
disease. About one in 20 patients with Graves' hyperthyroidism has 
moderate-to-severe Graves' ophthalmopathy. Corticosteroids have been the 
mainstay of treatment, but new evidence about immune mechanisms has provided a 
basis to explore other drug classes. Intravenous methylprednisolone pulses are 
more effective and better tolerated than oral prednisone in the treatment of 
active, moderate-to-severe Graves' ophthalmopathy. Rituximab has also been 
suggested as a possible replacement for intravenous corticosteroids. Two 
randomised controlled trials of rituximab reached seemingly contradictory 
conclusions-rituximab was not better with respect to the primary outcome 
(clinical activity score) than placebo in one trial (which, however, was 
confounded by rather long Graves' ophthalmopathy duration), but was slightly 
better than intravenous methylprednisolone pulses in the other (disease 
flare-ups occurred only in the latter group). On the basis of evidence published 
so far, rituximab cannot replace intravenous methylprednisolone pulses, but 
could have a role in corticosteroid-resistant cases. Open-label studies of 
tumour-necrosis-factor-α blockade had limited efficacy, but other studies showed 
that interleukin-6 receptor antibodies were effective. Results of randomised 
controlled trials investigating the efficacy of the IGF-1 receptor antibody 
teprotumumab and the interleukin-6 receptor antibody tocilizumab are expected 
shortly. Approaches that target the causal mechanism of Graves' ophthalmopathy 
(antibodies or antagonists that block thyroid-stimulating-hormone receptors) 
also look promising.