Novel approaches to the management of graves' ophthalmopathy.

Severe Graves' ophthalmopathy constitutes a complex therapeutic challenge and treatment outcome often is not satisfactory. Established methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Recently, the use of intravenous glucocorticoids has been shown to provide more favorable results than oral glucocorticoids. Novel treatments under investigation include somatostatin analogues, intravenous immunoglobulins and antioxidants. Low-dose immunosuppressive drugs (namely cyclosporine and, possibly, methotrexate) might be useful as an adjunct to established methods, particularly in view of a glucocorticoid-sparing action. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists, which are currently evaluated in rheumatoid arthritis and other autoimmune conditions, might constitute in the future a valuable tool for the management of eye disease. Prevention of Graves' ophthalmopathy would be desirable, but so far it is limited to secondary prevention (arrest of progression of subclinical disease to clinical disease) and tertiary prevention (avoidance of deterioration or complications of clinical disease): among preventive measures smoking withdrawal is probably the most important one. Primary prevention (in the absence of disease) is only speculative, but oral tolerance induction or vaccination with the offending antigen(s) might prove beneficial for prevention of Graves' ophthalmopathy in genetically susceptible individuals.