Cirić J, Zarković M, Stojanović M, Pepenezić Z, Randjelović G, Gligorović M, Trbojević B, Drezgić M, Nesović M
Institute of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Centre of Serbia, Belgrade.
Srp Arh Celok Lek. 2000 May-Jun;128(5-6):179-83.
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.
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.
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.
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
在所有格雷夫斯甲亢患者中，3% - 5%的患者会出现因压迫性视神经病变、眼外肌增厚和角膜暴露导致的严重眼病，伴有视力损害和复视[1]。超过50%的眼病患者选择使用类固醇进行治疗，超过70%的病例采用眼眶放疗或手术减压治疗[2]。在严重眼病患者中，超过60%的患者使用类固醇有效[1, 3]，但要达到有效效果需要高剂量[1, 4 - 6]。高剂量静脉注射类固醇脉冲疗法可能比口服类固醇更可取，其反应更好且副作用更少[6]。本研究的目的是评估高剂量静脉注射甲基强的松龙脉冲疗法随后口服类固醇治疗严重格雷夫斯眼病患者的疗效。
14例甲状腺功能正常的严重格雷夫斯眼病患者接受了为期6个月的高剂量静脉注射甲基强的松龙治疗，并通过临床和眼科评估进行了24 - 48个月的随访。在三天内，分两次给予甲基强的松龙，每次500 mg，溶于500 ml等渗盐水中静脉输注。治疗后给予口服泼尼松，每日40 mg，四周后减至10 mg，此时开始下一疗程治疗。类固醇治疗无禁忌证。该组患者的特征见表1。在研究过程中对角膜、眼外肌、眼睑、眼球突出和视神经功能状态进行了眼科评估。评估内容包括视力、眼压、视觉诱发电位、睑裂、眼球突出度、眼底检查、眼球运动评估、视野、色觉、兔眼和角膜变化。为了更好地评估眼病，使用了临床活动评分和患者自我评估。在研究过程中测量了甲状腺激素和甲状腺微粒体抗体。所有患者在治疗前后均拍照。治疗前后进行眼眶计算机断层扫描以评估眼外肌。数据采用威尔科克森检验进行分析。
所有患者在治疗的第一周内临床活动评分显著下降，并在随访期间保持稳定（治疗前：中位数为5，最小值为3，最大值为7；治疗后：中位数为2，最小值为1，最大值为4，p < 0.01）。眼球突出度（表2，图1）显著降低（治疗前后的平均值分别为24.15 mm和22.75 mm，差值为1.40 mm；p = 0.014）。5例患者中有2例视力得到改善（表3）。表4列出了对9例患者色觉、眼底变化、视野和眼压的眼科评估结果。9例患者中有5例在治疗3 - 6个月后复视消失或改善。10例患者中有9例眼球运动恢复正常或改善。眼眶CT扫描显示10例患者眼外肌增粗程度降低（治疗前后的平均评分分别为6.9和3.8）。治疗期间观察到轻微且短暂的副作用。
疾病严重程度和治疗反应的最佳参数是与视神经功能、眼球运动和角膜状态评估相关的参数[6, 10]。在这组接受高剂量类固醇治疗的14例患者中，我们发现治疗后几天内视力和色觉得到改善，视野、眼压、视觉诱发电位和眼底变化恢复正常。如大多数报告所示[3, 5, 8]，治疗显著且迅速地降低了临床活动评分（CAS）。由于CAS基于炎症体征，因此对治疗结果具有较高的预测价值。然而，低评分水平并不排除治疗成功[9]。治疗后眼球突出度的平均值显著降低。
