[Treatment of Grave's ophthalmopathy with high doses of corticosteroids].
Severe ophthalmopathy with sight impairment and double vision due to a compressive optic neuropathy, extraocular muscle thickness and corneal exposure occurs in 3-5% of all patients with Graves' hyperthyroidism [1]. Steroids are the choice of treatment for ophthalmopathy in more than 50%, and with orbital radiotherapy or surgical decompression in more than 70% of cases [2]. In severe ophthalmopathy steroids are effective in more than 60% of patients [1, 3], but to be effective high dosage is necessary [1, 4-6]. High-dose intravenous steroid pulse therapy is probably preferable to oral steroids giving a better response with fewer adverse effects [6]. The aim of the study was to evaluate the efficacy of high-dose intravenous methylprednisolone pulse therapy followed by oral steroids in the treatment of patients with severe Graves' ophthalmopathy.


METHODS
Fourteen euthyroid patients with severe Graves' ophthalmopathy were treated with high-dose intravenous methylprednisolone during 6 months and followed-up for 24-48 months by clinical and ophthalmological assessment. During three days two doses of methylprednisolone were given as 500 mg in 500 ml isotonic saline infusion. The treatment was followed by oral prednisone 40 mg daily and tapered off to 10 mg in four weeks when next course of therapy started. There were no contraindications for steroid treatment. Characteristics of the group are presented in Table 1. Ophthalmological assessment relating to the status of cornea, extraocular muscles, eyelids, proptosis and optic nerve function was done during the study. It provides the measurement of visual acuity, intraocular pressure, visual evoked potentials, palpebral apertures and proptosis, fundoscopy, the assessment of ocular motility, visual fields, color vision, lagophthalmos and corneal changes. For better evaluation of eye disease clinical activity score and patients self-assessment were used. Thyroid hormones and thyroid microsomal antibodies were measured during the study. All patients were photographed before and after treatment. Orbital computed tomograms were performed before and after treatment for extraocular muscles assessment. Data were analyzed by Wilcoxon test.


RESULTS
Clinical activity score fell significantly within the first week of therapy in all patients and remained stable during the follow-up period (before treatment: mediana 5, min 3, max 7 and after: mediana 2, min 1, max 4, p < 0.01). Proptosis (Table 2, Figure 1) was significantly reduced (mean values before and after treatment were 24.15 mm and 22.75 mm respectively, the difference was 1.40 mm; p = 0.014). Visual acuity was improved in 2 of 5 patients (Table 3). Ophthalmological assessment of color vision, fundal changes, visual fields and intraocular pressure is presented in Table 4. Five of 9 patients experienced loss or amelioration of diplopia after a 3-6 month treatment. The ocular motility was normalized or improved in 9 of 10 patients. The extraocular muscle enlargement on orbital CT scans decreased in 10 patients (mean score before and after treatment was 6.9 and 3.8 respectively). Minimal and transient side effects were observed during treatment.


CONCLUSIONS
The best parameters of severity of the disease and of response to treatment are those related to assessment of optic nerve function, ocular motility and corneal status [6, 10]. In this series of 14 patients treated with high-dose steroids we found an improvement in visual acuity and color vision and normalization of visual fields, intraocular pressure, visual evoked potentials and fundal changes within a few days of treatment. Clinical activity score (CAS) was significantly and promptly reduced by therapy as most reports revealed [3, 5, 8]. CAS has a high predictive value for the outcome of treatment since it is based on signs of inflammation. The low score level, however, does not preclude a therapeutic success [9]. A mean value of proptosis was significantly reduced by thera
Cirić
J
J
Institute of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Centre of Serbia, Belgrade.
Zarković
M
M
Stojanović
M
M
Pepenezić
Z
Z
Randjelović
G
G
Gligorović
M
M
Trbojević
B
B
Drezgić
M
M
Nesović
M
M
D000328:Adult; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006111:Graves Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage
D005938:Glucocorticoids; D011241:Prednisone; D008775:Methylprednisolone