Low- versus high-dose radiotherapy for Graves' ophthalmopathy: A randomized, single blind trial

Orbital radiotherapy (Rx) is a commonly used treatment for Graves' ophthalm opathy (GO), but controlled clinical trials evaluating different Rx doses a nd application forms have not been performed. In euthyroid patients with mo derately severe GO, we randomly compared the efficacy and tolerability of t hree Rx protocols. Orbital Rx (telecobalt) was administered either in 20 di vided fractions of 1 Gray (Gy) weekly over 20 weeks (group A) or in 10 frac tions of 1 Gy (B) and 2 Gy (C) daily over 2 weeks. Before and 24 weeks afte r starting Rx, ophthalmic investigation and magnetic resonance imaging were performed. Response to therapy, defined as a significant amelioration of t hree objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (5 5%) subjects (C us. A, P = 0.007). Ophthalmic symptoms and signs regressed most in group A; changes in lid fissure width were -1.5, -0.5, and 0 mm in the A, B, and C groups, respectively (A us. C, P = 0.005), whereas changes in intraocular pressure (upgaze) were -3, +1, and -1.5 mm Hg, respectively (A vs. B, P = 0.002). The median decreases in proptosis were -2 mm (A, P = 0.0001), -1.5 mm (B, P = 0.02), and -1 mm(C, P = 0.007; A vs. C, P = 0.0380 . Visual acuity(+ 0.15; P = 0.02) and eye muscle motility (bulbar elevation , 30 degrees vs. 37 degrees, P = 0.03, A us. C, P = 0.0020; abduction, 45 v s. 49 degrees, P = 0.02; A vs. C, P = 0.017) improved in group A only. A si gnificant change in all rectus muscle areas was noted in 14 A (78%), 12 B ( 55%), and 9 C (41%) subjects (C vs. A, P = 0.002). A decrease in the NOSPEC S classes was observed in 12 A (67%), 13 B (59%), and 13 C (59%) patients ( A us. B/C, P = 0.01). Rx-induced conjunctivitis was not observed in group A , but was seen in 4 B (18%) and 8 C (36%) subjects (C vs. A, P = 0.003). At 24 weeks, satisfaction rates were 67%, 59%, and 55% in the A, B, and C gro ups, respectively (C vs. A, P = 0.008). Thus, in patients with moderately s evere GO, similar response rates were observed for low and high Rx doses, b ut the 1 Gy/week protocol was more effective and better tolerated than the short arm regimens.