Graves' ophthalmopathy

I recently saw a woman with Graves’ disease. She had been diagnosed a few years ago and received radioactive iodine therapy. Her thyroid-stimulating hormone level is 1.17 on thyroid hormone therapy.

Prior to the radioactive iodine, she had no ocular symptoms. However, about one year afterward, she developed periorbital swelling and exophthalmos. An MRI confirmed Graves' ophthalmopathy. She went to an eye care specialist at a tertiary referral center and was treated with a course of high-dose glucocorticoids. The ocular disease appears to have stabilized. Her question was: What should be done next if her eye disease reactivates?

Although severe sight-threatening eye disease is rare, milder cases are common. The pathophysiology appears to be T-lymphocytes reacting with antigens shared by the thyroid and orbits. This results in release of cytokines, proliferation of fibroblasts and adipose tissue, and secretion of glycosaminoglycans from fibroblasts. Patients can develop manifestations such as eye pain, excessive tearing, lid lag, periorbital swelling, photophobia, exophthalmos and extraocular muscle dysfunction. In more severe cases, optic neuropathy can threaten vision.

Certain factors such as smoking are associated with worse disease. Smokers should be encouraged to quit. Both uncontrolled hypothyroidism and hyperthyroidism may promote disease progression. Special attention should be made to control abnormal thyroid function. Avoidance of post-radioactive iodine hypothyroidism and early initiation of levothyroxine may reduce risk of worsening eye disease. Some cases of pre-existing ophthalmopathy may progress after radioactive iodine therapy. In these situations, prophylactic glucocorticoids may be helpful. Antithyroid medications have not been associated with progression and may be an alternative to radioiodine therapy for patients with eye disease.

Patients with symptomatic or progressing ophthalmopathy are managed with high-dose oral or IV glucocorticoids. Other options are available for patients who fail to respond to glucocorticoids. Orbital radiotherapy has been used in patients with impaired eye mobility but is less effective in those with swelling and exophthalmos. Combination of radiotherapy with oral glucocorticoids appears to be more effective than either agent alone.

Other agents have also been studied. Cyclosporine is less effective than oral glucocorticoids but may allow reduction of dose of glucocorticoids. Rituximab (Rituxan, Genentech) may be beneficial but further study is needed. There does not appear to be any benefit with other agents such as somatostatin analogues and IV immune globulin.

In patients with severe eye disease, surgery is an option. If sight-threatening optic neuropathy is present and does not respond to high-dose IV glucocorticoids, the next step is orbital decompression. Other procedures can assist with cosmetic concerns but should be delayed until disease is inactive for at least six months.

I reassured my patient that often Graves' ophthalmopathy goes into remission and does not return. Nonetheless, I strongly encouraged her to continue to follow up with her eye care specialist to monitor disease activity.

For more information, I recommend the following case vignette and review: Bartalena L, Tanda ML. Graves' ophthalmopathy. N Engl J Med. 2009;360:994-1001.