Graves' orbitopathy: imperfect treatments for a rare disease.

Graves' orbitopathy (GO) is the most frequent and invalidating extrathyroidal expression of Graves' disease. Its incidence and prevalence are, however, low. About three quarters of Graves' patients have no GO at diagnosis, and moderate-to-severe and severe forms represent no more that 5-6% of cases. Progression to severe forms occurs rarely, but it may be caused by risk factors, the most important being smoking and poor control of thyroid dysfunction. Lot of progress has been recently achieved in the understanding of GO pathogenesis, while the disease remains a therapeutic challenge and dilemma. Common treatments for moderate-to-severe and active forms of GO (glucocorticoids and orbital radiotherapy) frequently provide incomplete responses and may be followed by relapse or progression of GO. After the disease has been inactivated by medical treatment, many patients need rehabilitative surgery for residual manifestations (orbital decompression for exophthalmos, squint surgery for extraocular muscle dysfunction, eyelid surgery for eyelid malposition). Novel pharmacological treatments are on the horizon and might target pathogenetic mechanisms of the disease better than glucocorticoids. Clinical evidence concerning their efficacy and safety is presently lacking.