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Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), 99mTc-labeled diethylene triamine pentaacetic acid (99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m2 body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 +/- 1.7 and decreased to 3.4 +/- 1.6 by one month (p < 0.05) and remained unchanged (3.2 +/- 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 +/- 4.51 MBq/cm3 and decreased to 11.97 +/- 2.36 MBq/cm3 at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 +/- 17.61 ms and 84.29 +/- 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 +/- 3.4 U/L, 5.6 +/- 4.5 U/L and 1.7 +/- 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. 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