Thyroid-associated ophthalmopathy: Clinical features, pathogenesis, and management

Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder chara cterized by immune-mediated inflammation of the extraocular muscles and orb ital connective tissue. TAO is linked, in a unique way, with thyroid autoim munity, in particular Graves' hyperthyroidism Our working hypothesis for th e pathogenesis of TAO is that recognition of a thyrotropin receptor (TSHR)- like protein in the orbital preadipocytes by antibodies may be the initial event leading to homing of lymphocytes into the orbital tissues. In the cou rse of thyroid inflammation, antibodies and T cells reactive against G2s ex pressed in thyroid membranes cross-react with the protein in the eye muscle fiber, leading to eye muscle damage and dysfunction. Those patients with a nti-G2s antibodies develop ocular myopathy. Antibodies against flavoprotein , the 64-kDa protein, which are produced in the context of eye muscle fiber damage and mitochondrial rupture, are sensitive markers of immune-mediated fiber necrosis in patients with ophthalmopathy but do not directly damage the eye muscle. Antibodies against type XIII collagen, which is localized i n the plasma membranes of orbital fibroblast, may be a new marker for the c ongestive ophthalmopathy subtype of TAO. The measurement of antibodies agai nst key eye muscle and orbital connective tissue autoantigens may have a ro le in the management of active ophthalmopathy and its prediction in patient s with Graves' hyperthyroidism.