Pathogenesis and treatment of the ophthalmopathy associated with Graves' disease.

The pathogenesis and etiology of the ophthalmopathy associated with Graves' disease still remains to be elucidated. There is, however, general consensus that the extraocular muscles are the principal site of the autoimmune response and that the main changes are in the interstitium. The primary target seems to be the fibroblasts which are stimulated as a result of cytokine release by the activated T-cells that accumulate in the muscles. Increased production of glycosaminoglycans and collagen by fibroblasts, attracts water to the interstitium and produces interstitial oedema. The frequent association of Graves' thyroid disease and ophthalmopathy favours the hypothesis of antibodies cross-reacting with antigens of orbit and thyroid. Although cross-reactivity is very attractive, the nature of the involved antigen remains unknown. Since Graves' ophthalmopathy is an autoimmune disorder, many immunomodulatory agents have been used in the treatment of this disorder. Anti-inflammatory and immunosuppressive treatment modalities will be reviewed.