Eighty-two consecutive patients with moderate-to-severe and active
Graves' ophthalmopathy were randomly treated with orbital
radiotherapy combined with either oral (
prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (
methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals)
glucocorticoids. The two groups did not differ for age, gender, duration of
hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine
therapy shortly before treatment for
Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in
proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv
glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 mm in oral
glucocorticoid group, P < 0.0001) and in lid width (from 13.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups.
Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv
glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral
glucocorticoid patients (P < 0.03). The degree of amelioration of
diplopia did not significantly differ between the two groups (P = 0.82).
Optic neuropathy improved in 11 of 14 iv
glucocorticoid (P < 0.01) and only in 3 of 9 oral
glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv
glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral
glucocorticoid group; final Clinical Activity Score was significantly lower in iv
glucocorticoid than in oral
glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv
glucocorticoid and 30 (73.2%) oral
glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv
glucocorticoid group (36 of 41, 87.8%) were more than in the oral
glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv
glucocorticoid treatment was better tolerated than oral
glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv
glucocorticoid and 35 (85.4%) oral
glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv
glucocorticoid patient had severe
hepatitis of undetermined origin at the end of
glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv
glucocorticoid and oral
glucocorticoid (associated with orbital
radiotherapy) are effective in the management of severe
Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.