Long-Term Safety of Orbital Radiotherapy for Graves’ Ophthalmopathy

Abstract

We investigated the long-term side-effects of orbital radiotherapy (OR) in 204 patients with Graves' ophthalmopathy (GO), irradiated from 1972-1996 [44 by cobalt unit (CU) and 160 by linear accelerator (LA), mostly combined with glucocorticoids], with a 5- to 25-yr follow-up (median, 11 yr). Cataract was observed in 21 patients (10%) 3-21 yr after OR, with a higher (not significant) prevalence in CU-treated patients (18% vs. 8% in LA-treated patients). The prevalence of cataract was higher, although not significantly, in CU-treated patients aged less than 60 yr, but not in LA-treated patients, compared with the general population. Mild, asymptomatic retinopathy was observed in 1 of 7 patients (14%) with diabetes and hypertension, in 1 of 31 patients (3%) with hypertension alone, and in 0 of 11 patients with diabetes alone. No tumors were observed in 157 patients submitted to computed tomography scan of orbital and adjacent regions. In conclusion, OR is a safe treatment, not associated with an increased frequency of cataract, provided a high voltage apparatus is used. Hypertension, especially if associated with diabetes, may represent a relative contraindication, as it may cause retinopathy. Although no secondary tumors were detected, due to the long latency of radiation-induced tumors, OR should be restricted to patients older than 35 yr.

Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO

“…OR is usually well tolerated, but may cause transient exacerbation of ocular symptoms, which is preventable with concomitant GC administration (3,66). Data on long-term safety are reassuring (76)(77)(78), but theoretical concerns about carcinogenesis remain for younger patients, particularly those under the age of 35 years (70,(76)(77)(78). Although cataracts can occur earlier after OR than naturally, they are easily treated by surgery.…”

“…Retinal microvascular abnormalities have been detected in a minority of patients (79), mostly in those with concomitant severe hypertension or diabetic retinopathy, and these two comorbidities are considered absolute contraindications to OR (80,81). It is possible that diabetes, even in the absence of retinopathy, represents a risk factor for the development of retinal changes after OR (78), but the evidence is less clear (77). Thus, diabetes without retinopathy may be regarded as a relative contraindication to OR (see also Box 12).…”

“…† In the rare event of reactivation of GO after rehabilitative surgery, systemic GCs, and/or OR can be used with the usual expected efficacy (99). (77,78,80,81), at least using a 20 Gy cumulative dose. † Diabetes and/or hypertension are not contraindications to surgical orbital decompression or other surgical treatments for GO.…”

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

“…In general, the administered dose is 20 Gray (Gy) per orbit fractionated in 10 daily doses over 2 weeks (78), but also 1 Gy per week over a 20-week period was shown to be equally effective and better tolerated (79). Irradiation therapy may induce mild and transient exacerbation of ocular inflammation that can be controlled by the concomitant administration of low-dose GCs (3,80), whereas reports on long-term safety have been reassuring (81,82). To date, there has been no evidence that intravenous GCs associated with orbital radiotherapy is more effective than steroids alone, but this interesting hypothesis will be challenged in a randomized multicenter clinical trial conducted among EUGOGO centers.…”

Acute thyroid eye disease (TED): Principles of medical and surgical management

“…44 In moderately severe non-sight-threatening disease, radiotherapy combined with intravenous methylprednisolone is effective in 88% of patients, this being more effective than oral prednisolone and radiotherapy. Radiotherapy should be used with caution in diabetic patients (particularly in those who are also hypertensive, due to the risk of new or deteriorating diabetic retinopathy), 47 and preferably restricted to patients older than 35 years of age due to the long latency of radiotherapy-induced tumours.…”