Retrobulbar irradiation for thyroid-associated orbitopathy: double-blind comparison between 2.4 and 16 Gy.

Purpose: Retrobulbar irradiation is used as a standard therapy for thyroid-associated orbitopathy. The evidence of its effectiveness is, however, scarce. Doses from 2.5 to 20 Gy have been recommended.
Methods: Forty-three patients with active thyroid-associated orbitopathy were irradiated with 2.4 Gy and 43 with 16 Gy. Five measures of outcome were used: (1) appearance of the eye region, documented with photographs; (2) Hertel exophthalmometry; (3) range of vertical eye movements; (4) eye muscle thickness (sum of three MRI sections across the eight rectus eye muscles); and (5) complaints, indicated on a visual analog scale.
Results: At 3 and 6 months after irradiation, no difference between 2.4 and 16 Gy was found in any of the five outcome measures (p between 0.099 and 0.993; Kruskal-Wallis test, Holm correction). Most outcome measures were slightly, but not significantly, improved in both the 2.4 and the 16 Gy groups. Patient complaints had improved significantly in both groups and the eye muscle thickness was significantly reduced in the 2.4 Gy group after 6 months.
Conclusion: The lack of a difference between 2.4 and 16 Gy is compatible with four different interpretations: (1) the irradiation could be ineffective; (2) the maximal effect could be already reached at 2.4 Gy; (3) the maximal effect could lie between 2.4 and 16 Gy; and (4) the effect could increase beyond a threshold of >or=16 Gy. From general experience with inflammatory disease, the last two possibilities are unlikely; only the first two interpretations carry some probability. Although the design of the study did not allow a distinction between these two possibilities, we conclude that retrobulbar irradiation for thyroid-associated orbitopathy should not exceed 2.4 Gy.