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Use of Radiotherapy in Graves' Orbitopathy



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Am Fam Physician. 2000 Oct 15;62(8):1896-1898.

The inflammatory changes of the orbit in some cases of Graves' disease are believed to be autoimmune reactions. Many cases are mild and self-limiting, but some produce significant pain, visual disturbance and swelling of the eyelids and surrounding tissues. The condition can progress to fibrosis and may be vision-threatening. Many treatments have been used for Graves' orbitopathy, including corticosteroids, cyclosporine, surgery, plasmapheresis and radiotherapy, but the optimal therapy for individual patients has not been determined. Mourits and colleagues examined the effect of radiotherapy in a double-blind, placebo-controlled trial.

They studied patients with moderately severe Graves' orbitopathy, defined as motility impairment causing diplopia, proptosis of at least 23 mm or severe eyelid swelling. Patients with mild disease and those with evidence of optic nerve compression were excluded from the study. All patients were treated with drugs to maintain a euthyroid state by blocking natural hormone secretion with an antithyroid drug and replacing indigenous hormone with levothyroxine. On entry to the study, patients were required to have been euthyroid for at least three months. The 30 patients were randomly assigned to retrobulbar irradiation of 20 Gy in 10 fractions over 12 days or simulated irradiation during which lead markers covered the eyes and no radiation was delivered to the orbital tissues.

Patients were assessed one day before starting therapy and at four, 12 and 24 weeks after treatment. Various standardized measurements of eyelid swelling, proptosis, eye mobility, visual acuity and corneal status were obtained at each visit. Patients were also asked to record and rate visual symptoms.

Measures of thyroid function did not differ between the groups throughout the study. Treatment was assessed as successful in 18 (60 percent) of irradiated patients compared with nine (31 percent) of the patients receiving “sham” treatments. This improvement was limited to reduction of diplopia because of improvements in motility. Eyelid swelling and proptosis were not significantly improved in patients receiving radiation. Motility improved in 14 (82 percent) patients after radiotherapy and in four (27 percent) of those in the control group. The only adverse effects of therapy were transient skin erythema and local hair loss in three irradiated patients.

In spite of therapy, most patients required further treatment. Three patients in the irradiated group required steroids and three in the control group required irradiation. Nine irradiated and 14 control patients required surgical decompression. The authors report that equal and significant numbers of patients from each group received surgical corrections after the study, including extraocular muscle repair (10 in each group), eyelid retraction repair (15 irradiated patients and 12 control subjects), and blepharoplasty (13 irradiated patients and nine control subjects).

The authors conclude that the role of radio-therapy in moderately severe Graves' orbitopathy is restricted to patients with motility impairment. Even in this group, the number of patients who were spared additional treatment, including surgery, was modest. Although radio-therapy is safe, it should not be used in patients with diabetes mellitus because of concerns that radiation accelerates retinal vascular changes.

Mourits MP, et al. Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study. Lancet. April 29, 2000;355:1505–9.



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