Cytokines appear to play a major role in thyroid-associated ophthal- mopathy. There is infiltration of the extraocular muscles by activated T cells; the release of cytokines such as interferon γ (IFN-γ), tumor necrosis factor (TNF), and interleukin-1 (IL-1) results in fibroblast acti- vation and increased synthesis of glycosaminoglycans that trap water, thereby leading to characteristic muscle swelling. Late in the disease, there is irreversible fibrosis of the muscles. Though the pathogenesis of thyroid-associated ophthalmopathy remains unclear, there is mounting evidence that the TSH-R is a shared autoantigen that is expressed in the orbit; this would explain the close association with autoimmune thy- roid disease. Increased fat is an additional cause of retrobulbar tissue expansion. The increase in intraorbital pressure can lead to proptosis, diplopia, and optic neuropathy.