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Ophthalmopathy may be particularly severe in 3% to 5% of patients with GD. The ocular manifestations of GD appear more frequently in women than men. Although it usually presents concomitantly with hyperthyroidism, it may precede or follow clinical hyperthyroidism (50). An area of controversy is whether treatment with radioiodine is associated with the onset or worsening of Graves' ophthalmopathy. Exacerbation of ophthalmopathy has been attributed to radioiodine-induced release of antigens shared by the thyroid and orbit. Conflicting results from studies of ophthalmopathy and RAI may be attributed to the retrospective and nonrandomized nature of most studies, inadequate control groups, and the nonstandardized assessment of ocular changes. Progression of ophthalmopathy may occur in approximately 15% of patients, especially those who smoke, have pre-existing eye disease, high levels of TSH-receptor antibody, or severe manifestations of thyroid disease (51). Cigarette smoking has been associated with an increased risk for progression of ophthalmopathy following radioiodine therapy, and a decreased efficacy of orbital radiation and glucocorticoid therapy (52).

Concomitant treatment with glucocorticoids can protect against the progression of opthalmopathy in patients with nonsevere ophthalmopathy (53,54). As worsening of pre-existing eye disease is more frequent than new ophtha-lmopathy following RAI treatment, patients most likely to benefit from corticos-teroids are those with clinically evident eye disease, especially if they continue smoking. Prednisone, 0.4-0.5 mg/kg per day, beginning immediately after radioiodine treatment, continued for one month, and then tapered over three months, has been shown to be effective in a randomized controlled trial (53). As both hyperthyroidism and corticosteroids may increase bone turnover, patients receiving long-term corticosteroids should be considered for evaluation of bone density and therapies to prevent osteoporosis. Pretreatment with methi-mazole does not appear to prevent the development or exacerbation of ophthal-mopathy after RAI treatment (55). Patients with more severe ophthalmopathy should receive prompt evaluation and treatment independent of RAI. Treatment for significant ocular disease includes high-dose glucocorticoids, orbital radiotherapy, orbital decompression, or a combination thereof. Patients with Graves' ophthalmopathy should be strongly encouraged not to smoke.

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