Patients with serious inflammatory Graves' ophthalmopathy should be treated with anti-inflammatory drugs or radiotherapy to prevent complications like fibrosis, while those with non-inflammatory ophthalmopathy may be treated by surgery immediately. It is often difficult, however, to distinguish inflammatory from non-inflammatory Graves' disease. We therefore present a simple clinical classification here to differentiate between these two conditions. This classification is based on the classical signs of inflammation-pain, redness, swelling, and impaired function. After two consecutive clinical examinations an 'activity score' can be determined, ranging from 0 to 10 points. In a retrospective study testing the efficacy of this classification we found that patients with an activity score of 3 or more at the beginning of therapy responded well to anti-inflammatory drugs, while those with a lower activity score mostly did not. Comparing the pretreatment activity score with the degree of enlargement of the extraocular muscles on the CT scan, we found a significant correlation between these two parameters: the higher the activity score, the more the enlargement of the muscles. We conclude that this classification facilitates the proper selection of patients for treatment. *An abridged classification of eye changes in Graves' ophthalmopathy'' : class (0): no physical signs or symptoms; (1) only signs, no symptoms (signs limited to upper lid retraction, stare, and lid lag); (2) soft-tissue involvement (symptoms and signs); (3) proptosis; (4) extraocular muscle movement: (5) corneal involvement; (6) sight loss (optic nerve insolvement).

It is uncertain what is the most appropriate medical therapy for patients with severe Graves' ophthalmopathy. Therefore, we carried out a single-blind, randomized clinical trial to compare the efficacy of prednisone with that of cyclosporine in 36 patients who had been euthyroid for at least two months. The two groups, each consisting of 18 patients, were similar in age, sex, and the duration and severity of ophthalmopathy. The initial dose of cyclosporine was 7.5 mg per kilogram of body weight per day, and that of prednisone was 60 mg per day, which was subsequently tapered to 20 mg per day. During the 12-week treatment period, 11 prednisone-treated and 4 cyclosporine-treated patients responded to therapy (61 percent vs. 22 percent; P = 0.018); response was manifested by decreases in eye-muscle enlargement and proptosis and improved visual acuity and total and subjective eye scores. There were no differences at base line between the patients who later responded and those who did not. Prednisone was tolerated less well than cyclosporine. After 12 weeks, patients who did not respond were treated for another 12 weeks with a combination of cyclosporine and a low dose of prednisone. Among the 9 patients who initially received prednisone, the addition of cyclosporine resulted in improvement in 5 (56 percent); among the 13 patients who received cyclosporine initially, 8 (62 percent) improved after the addition of prednisone. Combination therapy was better tolerated than prednisone treatment alone. We conclude that single-drug therapy with prednisone is more effective than cyclosporine in patients with severe Graves' ophthalmopathy. The combination can be effective in patients who do not respond to either drug alone.

No abstract

The eye findings of Graves’ ophthalmopathy were prospectively recorded in 90 consecutive untreated patients (66 females, 24 males; mean age 44.5 years) according to the 1977 NOSPECS classification. Soft-tissue involvement was observed in 90%, proptosis ≥ 23 mm in 30%, eye muscle involvement in 60%, corneal involvement in 9% and sight loss in 34%. No differences in the distribution of eye changes between right and left eye were found. Values for proptosis (mean ± SD, 20.2 ± 3.6 mm) had a near-normal distribution. Orbital computed tomography (CT) scanning (performed in 80 cases) demonstrated enlargement of inferior rectus in 60%, medial rectus in 50%, superior rectus in 40% and lateral rectus in 22%. Unilateral eye disease was present in 13 patients (14%); in 4 of these patients the CT scan showed eye muscle enlargement also in the fellow eye and in 2 patients bilateral eye disease subsequently developed. The distribution of age, sex and NOSPECS classes in patients with unilateral eye disease was similar to that in patients with bilateral eye disease, but the interval between the onset of thyroid and eye disease was much shorter in cases of unilateral than in cases of bilateral eye disease. Patients without clinically evident thyroid disease (n = 20, 22%) were not different from patients with thyroid disease in age, sex or ophthalmological presentation. The various data suggest: (1) the 1977 NOSPECS classification underrepresents significant proptosis in 12% of cases; (2) the age and sex distribution of patients with Graves’ ophthalmopathy is similar to that of cases with thyroidal Graves’ disease, and (3) unilateral Graves’ ophthalmopathy may represent an early stage of the disease, that as a rule already is or develops shortly afterwards into a bilateral disease.

The temporal relationship between the onset of Graves' ophthalmopathy and the onset of thyroidal Graves' disease was evaluated in 125 consecutive patients with Graves' ophthalmopathy. Thyroidal Graves' disease--past or present--was clinically evident in 99 patients (79%): hyperthyroidism in 3 cases. Thyroid disease preceded the eye disease in 37 patients, it occurred simultaneously with the eye disease in 39 patients, and it developed after the eye disease in 23 patients (in 16 cases within one yr after the onset of eye disease). The age at the onset of thyroid disease (38.7 +/- 12.9 yr) was lower than the age at the onset of ophthalmopathy (41.8 +/- 12.5 yr; p less than 0.001). Among the 26 clinically euthyroid patients (21%) laboratory evidence of thyroidal Graves' disease was found in 14 cases (11%): abnormal TRH test, n = 9; normal TRH test but abnormal T3-suppression test, n = 4; normal TRH and T3-suppression tests but positive thyroid stimulating antibodies, n = 1). We conclude that Graves' ophthalmopathy as a rule develops at a time when thyroid autoimmunity also exists. This strongly suggests a common factor in the pathogenesis of thyroidal and ocular expressions of Graves' disease.