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

Abstract

Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue. TAO is linked, in a unique way, with thyroid autoimmunity, in particular Graves' hyperthyroidism. Our working hypothesis for the 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 course of thyroid inflammation, antibodies and T cells reactive against G2s expressed in thyroid membranes cross-react with the protein in the eye muscle fiber, leading to eye muscle damage and dysfunction. Those patients with anti-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 in the plasma membranes of orbital fibroblast, may be a new marker for the congestive ophthalmopathy subtype of TAO. The measurement of antibodies against key eye muscle and orbital connective tissue autoantigens may have a role in the management of active ophthalmopathy and its prediction in patients with Graves' hyperthyroidism.