甲基强的松龙静脉冲击及眼眶放射治疗甲状腺相关眼病的系统评价

发布时间：2018-06-14 22:47

本文选题：甲状腺相关眼病 + 甲基强的松龙　；参考：《第二军医大学》2012年硕士论文

【摘要】：目的甲状腺相关眼病（Thyroid-associated ophthalmopathy, TAO）是自身免疫性甲状腺疾病在眼部的一种炎症表现，部分患者会出现严重的眼部症状和体征而需要积极治疗，主要治疗方法有免疫抑制剂、眼眶放射治疗、外科手术、生长抑素类似物及免疫球蛋白治疗等，其中较常见的是甲基强的松龙静脉冲击、眼眶放射治疗和眼眶减压术。但是，甲基强的松龙静脉冲击和眼眶放射治疗的有效性及安全性，以及甲基强的松龙静脉冲击联合应用眼眶放疗的有效性均需要进行深入的研究。虽然既往已经发表近百篇关于TAO治疗的随机对照临床试验，但结果并不一致，甚至自相矛盾。我们通过对以往发表的所有关于甲基强的松龙静脉冲击和眼眶放射治疗的随机对照临床试验进行系统评价和Meta分析，以明确两者治疗TAO的有效性和安全性。资料和方法根据预先设计的研究方案进行系统评价。通过系统全面的检索，获取既往发表的关于甲基强的松龙静脉冲击和眼眶放射治疗TAO的随机对照临床试验。电子检索数据库包括PubMed、Embase、Cochrane临床对照试验注册中心、中国生物医学文献数据库、相关期刊论文、中文科技期刊全文数据库和万方数据库，检索截止日期为2011年5月31日，并手工检索纸质杂志及参考文献作为补充。研究对象包括：未经其他方法治疗的中或重度活动期TAO患者。干预措施包括：甲基强的松龙静脉冲击、眼眶放射治疗或两者联合治疗。有效性指标为：治疗后患者眼部症状、体征、辅助检查结果和主观感受中的1项较治疗前好转。安全性指标为：副作用的发生率。通过严格的筛选流程，总计纳入12项随机对照临床试验：甲基强的松龙静脉冲击治疗7项、眼眶放射治疗5项。采用Jadad量表或Cochrane Handbook for Systematic Reviewsof Interventions5.0.2质量评价标准进行定量化的质量评估。采用意向性分析原则进行临床终点的评估。Meta分析采用Cochrane系统评价软件RevMan5.0和RevMan5.1，统计方法选择DerSimonian-Laird法随机效应模型；二分类变量采用相对危险度（RR）或比值比（OR）及其95%可信区间（confidence interval，CI），连续性变量则采用加权均数差(weighted mean difference，WMD)及其95%CI。结果 ①甲基强的松龙静脉冲击：总计360例患者，平均年龄45.3岁，男女性别比1∶3.14，，包括79例甲基强的松龙静脉冲击联合眼眶放射治疗、100例甲基强的松龙静脉冲击、78例强的松口服联合眼眶放射治疗、88例强的松口服、9例安慰剂和6例眼眶减压术。根据Jadad量表的评分标准所有被纳入文献的评分结果为：1项试验为5分、3项试验为4分、1项试验为3分，1项试验为1分，1项试验为0分。甲基强的松龙静脉冲击与安慰剂相比的RR(95%CI)为7.50[1.14,49.26]，与眼眶减压术相比的RR(95%CI)为3.33[0.51,21.89]，与口服糖皮质激素相比的合并RR(95%CI)为1.48[1.18,1.87]。甲基强的松龙静脉冲击联合眼眶局部放疗与口服糖皮质激素联合眼眶局部放疗相比的合并RR(95%CI)为1.42[1.11,1.81]。 ②眼眶放射治疗：总计289例患者，平均年龄46.7岁，男女性别比1∶2.94。包括165例眼眶放射治疗、50例强的松口服和116例假放疗。根据Cochrane Handbookfor Systematic Reviews of Interventions5.0.2质量评价标准所有被纳入文献的评分结果为：1项试验为A级质量，4项试验为B级质量。眼眶放射治疗与假放疗相比的OR(95%CI)为0.32[0.16,0.64]，眼眶放射治疗与口服糖皮质激素相比的OR(95%CI)为0.89[0.40,1.94],眼眶放疗对突眼症状改善的合并均数差(95%CI)为-0.30[-0.69,0.10]。结论 ①大剂量甲基强的松龙静脉冲击治疗是中或重度活动性TAO的有效治疗方法，联合应用眼眶局部放射治疗可提高疗效。Meta分析的结果显示，无论糖皮质激素静脉冲击或口服，经过治疗后，临床活动积分均明显下降，与治疗前有明显的差异，对TAO的临床症状均有明显缓解，说明糖皮质激素治疗是一个有效的手段，但是糖皮质激素静脉冲击的治疗作用更优于口服。糖皮质激素治疗的副作用和并发症在静脉冲击或口服后均能见到，主要是类库欣综合征、糖耐量减低、消化道症状、高血压、精神异常等。类库欣综合征是发生率较高的并发症之一，尤以口服治疗多见，两组间差异有显著性。 ②眼眶放疗可以有效治疗中或重度活动性TAO，与假放疗相比有明显统计学差异；眼眶放疗的治疗效果与口服糖皮质激素相当，二者无明显差异；眼眶放疗对突眼症状的改善无明显效果。综上所述，甲基强的松龙静脉冲击是中或重度活动性TAO目前较有效的治疗，作用显著优于糖皮质激素口服，联合应用眼眶局部放射治疗可提高疗效。而且，甲基强的松龙静脉冲击的耐受性高，安全性好。因此，甲基强的松龙静脉冲击可以作为治疗中或重度活动性TAO的首选。
[Abstract]:objective
Thyroid associated ophthalmopathy (Thyroid-associated ophthalmopathy, TAO) is an inflammatory manifestation of autoimmune thyroid disease in the eye. Some patients have serious ocular symptoms and signs and need to be treated actively. The main treatment methods are immunosuppressive, orbital radiotherapy, surgery, somatostatin analogues and immunity. Globulin therapy, among which the most common is methylprednisolone, orbital radiotherapy and orbital decompression. However, the effectiveness and safety of methylprednisolone and orbital radiotherapy, as well as the effectiveness of methylprednisolone venous impact combined with orbital radiotherapy, need to be studied in depth. However, nearly a hundred randomized controlled clinical trials of TAO therapy have been published in the past, but the results are inconsistent and even contradictory. We have made systematic evaluation and Meta analysis of all the previously published randomized controlled clinical trials of methylprednisolone venous impact and orbital radiotherapy to clarify the effectiveness of both treatment of TAO. Sex and safety.
Information and methods
A systematic review is conducted according to a pre designed study. Through systematic and comprehensive retrieval, a randomized controlled randomized controlled trial of methylprednisolone venous impact and orbital radiotherapy for TAO is obtained. The electronic retrieval database includes the PubMed, Embase, Cochrane clinical alignment center, and Chinese biomedical literature data The Chinese journal full text database, the full text database of Chinese sci-tech periodicals and the Wanfang database, the search cut-off date is May 31, 2011, and the manual retrieval of paper magazines and references is supplemented. The study includes: TAO patients in the medium or severe active period without other methods. Intervention includes: methylprednisolone Pulse shock, orbital radiotherapy, or combination of the two. The effectiveness index is: 1 items of eye symptoms, signs, auxiliary examination results and subjective feelings after treatment. Safety index is the incidence of side effects. Through a strict screening process, a total of 12 randomized controlled clinical trials are included: methylprednisone 7 items of dragon vein impact therapy, 5 cases of orbital radiotherapy. Quantitative evaluation was performed using Jadad scale or Cochrane Handbook for Systematic Reviewsof Interventions5.0.2 quality evaluation criteria. The clinical end point assessment was evaluated by intention analysis principle. Cochrane system evaluation software RevMan5.0 and RevMan5.1 were used. The statistical method selects the DerSimonian-Laird random effect model; the two classification variables use the relative risk degree (RR) or the ratio Ratio (OR) and the 95% confidence interval (confidence interval, CI), and the continuity variables use the weighted mean number difference (weighted mean difference, WMD) and its 95%CI.
Result
(1) methylprednisolone venous impact: a total of 360 patients, with an average age of 45.3 years of age, and sex ratio of 1 to 3.14, including 79 cases of methylprednisolone intravenous shock combined with orbital radiotherapy, 100 cases of methylprednisolone venous shock, 78 prednisone oral orbital radiotherapy, 88 prednisone oral, 9 placebos and 6 cases of orbital subtraction. According to the Jadad scale, all the scores included in the literature were 5 points, 3 trials for 4, 1 for 3, 1 for 1, 1 for 0.
RR (95%CI) of methylprednisolone compared with placebo was 7.50[1.14,49.26], RR (95%CI) compared with orbital decompression was 3.33[0.51,21.89], combined with oral glucocorticoid, RR (95%CI) combined with 1.48[1.18,1.87]. methylprednisolone intravenous impact combined orbital radiotherapy with oral glucocorticoid combined orbital part of orbit. RR (95%CI) was 1.42[1.11,1.81]. compared with radiotherapy
(2) orbital radiotherapy: a total of 289 patients, the average age of 46.7 years old, and sex ratio 1: 2.94. including 165 cases of orbital radiotherapy, 50 cases of prednisone oral and 116 case of false radiotherapy. According to the Cochrane Handbookfor Systematic Reviews of Interventions5.0.2 quality evaluation standard all included in the literature score results: 1 trials of A Grade quality, 4 tests for grade B.
The OR (95%CI) of orbital radiotherapy compared with that of false radiotherapy was 0.32[0.16,0.64], and OR (95%CI) of orbital radiotherapy compared with oral glucocorticoid (95%CI) was 0.89[0.40,1.94], and the combination of orbital radiotherapy for improvement of exophthalmos (95%CI) was -0.30[-0.69,0.10]..
conclusion
(1) high dose methylprednisolone intravenous impact therapy is an effective treatment for moderate or severe active TAO. Combined application of orbital local radiation therapy can improve the efficacy of.Meta analysis. The clinical symptoms of TAO were significantly relieved, indicating that glucocorticoid therapy was an effective means, but the therapeutic effect of glucocorticoid on venous impact was better than that of oral administration.
The side effects and complications of glucocorticoid treatment can be seen in both venous impact or after oral administration, mainly such as Cushing syndrome, impaired glucose tolerance, digestive tract symptoms, hypertension, and psychosis. One of the higher incidence of complications is Cushing syndrome, especially oral treatment. The difference between the two groups is significant.
(2) orbital radiotherapy can effectively treat moderate or severe active TAO, and there is significant difference compared with that of false radiotherapy. The therapeutic effect of orbital radiotherapy is similar to that of oral glucocorticoid. There is no significant difference between the two cases. The improvement of orbital radiotherapy has no obvious effect on the improvement of the exophthalmos.
To sum up, methylprednisolone venous impact is a more effective treatment of moderate or severe active TAO, which is significantly better than glucocorticoid oral administration. Combined use of orbital local radiation therapy can improve the efficacy. Moreover, methylprednisolone venous impact is well tolerated and safe. Therefore, the methylprednisolone venous impact can be used as a result. It is the first choice for the treatment of moderate or severe active TAO.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R771.3

【参考文献】