Interventions for central serous chorioretinopathy: a network meta-analysis.
Interventions for central serous chorioretinopathy: a network meta-analysis.
复制标题
DOI：
10.1002/14651858.cd011841.pub2
复制
发表时间：
2015-12-22
影响因子：
8.4
通讯作者：
Gehlbach, Peter
中科院分区：
文献类型：
--
作者：
Salehi, Mahsa;Wenick, Adam S.;Law, Hua Andrew;Evans, Jennifer R.;Gehlbach, Peter
中枢性浆液性脉络膜视网膜病变（CSC）以神经视网膜浆液性脱离伴脉络膜和视网膜色素上皮（RPE）功能障碍为特征。对视网膜的影响通常是自我限制的，尽管有些人由于进行性和永久性的光感受器损伤或RPE萎缩而留下不可逆的视力丧失。在CSC中使用了多种干预措施，包括但不限于激光治疗、光动力治疗（PDT）和玻璃体内注射抗血管内皮生长因子（anti-VEGF）药物。然而，尚不清楚这些或其他治疗方法是否比观察或其他干预措施具有显著优势。目前，对CSC的管理尚未形成循证共识。由于在很大程度上倾向于CSC自发消退或遵循一个盛衰过程，最常见的初始治疗方法是观察。目前尚不清楚这是否是安全性和有效性方面的最佳方法。比较中枢性浆液性脉络膜视网膜病变干预措施的相对有效性。我们检索了CENTRAL（包含Cochrane Eyes and Vision Trials Register）（2015年第9期）、Ovid MEDLINE、Ovid MEDLINE In-Process和其他非索引引文、Ovid MEDLINE Daily、Ovid OLDMEDLINE（1946年1月至2014年2月）、EMBASE（1980年1月至2015年10月）、ISRCTN注册表（www.isrctn.com/editAdvancedSearch）、ClinicalTrials.gov （www.clinicaltrials.gov）和世界卫生组织（WHO）国际临床试验注册平台（ICTRP） （www.who.int/ictrp/search/en）。我们在电子检索中没有使用任何日期或语言限制。我们最后一次检索电子数据库是在2015年10月5日。随机对照试验（rct）比较任何干预CSC与任何其他干预CSC或对照。两位综述作者独立选择研究和提取数据。我们使用固定效应模型汇总了所有研究的数据。对于应用于眼睛的干预措施（即非系统性干预措施），我们在网络荟萃分析模型中综合了直接和间接证据。我们纳入了25项研究，涉及1098名参与者（1098只眼睛），随访时间从16周到12年。研究在欧洲、北美和南美、中东和亚洲进行。这些试验规模较小（大多数试验招募的参与者少于50人），而且报道不佳；通常不清楚是否已经完成了审判的关键方面，例如拨款隐瞒。相当大比例的试验没有被掩盖。这些研究考虑了多种治疗方法：抗vegf（雷尼单抗、贝伐单抗）、PDT（全剂量、半剂量、30%、低剂量）、激光治疗（氩、氪和微脉冲激光）、受体阻滞剂、碳酸酶抑制剂、幽门螺杆菌治疗和营养补充剂（Icaps、叶黄素）；每次比较只有一两个试验提供数据。我们降低了大多数分析的偏倚和不精确风险，反映了研究的局限性和不精确的估计。网络荟萃分析（如我们方案中计划的那样）由于缺乏试验和非传递性问题，特别是急性或慢性CSC，无法帮助解决这种不确定性。来自两项试验的低质量证据表明，抗vegf（雷尼单抗或贝伐单抗）或观察急性CSC 6个月时视力变化的效果差异不大(平均差值（MD） 0.01 LogMAR（最小分辨角的对数），95%置信区间(CI) - 0.02至0.03；64名参与者)。6个月后，所有参与者的CSC都得到了缓解。没有发现明显的不良反应。一项研究（58名参与者）的低质量证据表明，与假手术治疗相比，半剂量PDT治疗急性CSC可能导致视力的轻微改善（MD - 0.10 logMAR, 95% CI - 0.18至- 0.02），12个月的复发率（风险比（RR） 0.10, 95% CI 0.01至0.81）和持续性CSC （RR 0.12, 95% CI 0.01至1.02）减少。没有发现明显的不良事件。来自两项试验（56名参与者）的低质量证据比较了慢性CSC的抗vegf和低影响PDT，发现12个月时视力有任何差异的证据很少（MD 0.03 logMAR, 95% CI - 0.08至0.15）。有证据表明，与接受PDT治疗的患者相比，抗vegf组中有更多的人复发性CSC，但由于试验之间的不一致性，很难估计其效果。抗vegf组中更多的人在12个月时出现持续性CSC （RR 6.19, 95% CI 1.61至23.81；34名参与者）。两项微脉冲激光的小型试验，一项在急性CSC患者中，一项在慢性CSC患者中，提供了低质量的证据，证明激光治疗可能导致更好的视力（MD - 0.20 logMAR, 95% CI - 0.30至- 0.11；45名参与者）。没有发现明显的不良反应。其他比较基本上没有定论。我们确定了12项正在进行的试验，包括以下干预措施：阿布西普和依普利酮在急性CSC中的应用；螺内酯、依普利酮、叶黄素、PDT和微脉冲激光治疗慢性CSC；微脉冲激光和口服米非司酮在两项试验中，CSC的类型没有明确规定。CSC仍然是一种谜一般的疾病，这在很大程度上是由于在很大比例的人群中自发改善的自然史，也因为在已发表的随机对照试验中，没有一种治疗方法提供了压倒性的疗效证据。虽然已经提出了一些可能有效的干预措施，但研究设计的质量、研究的执行以及相对较少的参与者登记和随访以揭示终点限制了现有数据的效用。目前尚不清楚治疗急性CSC是否有临床重要的益处，急性CSC通常作为其自然史的一部分自发消退。将个体治疗与自然史进行比较的随机对照试验对于确定潜在的治疗组进行正面比较是有价值的。在迄今为止研究的干预措施中，PDT或微脉冲激光治疗似乎最有希望在未来的试验中进行研究。
Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. To compare the relative effectiveness of interventions for central serous chorioretinopathy. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model. We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked. The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC. Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) −0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted. Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD −0.10 logMAR, 95% CI −0.18 to −0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted. Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI −0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants). Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD −0.20 logMAR, 95% CI −0.30 to −0.11; 45 participants). There were no significant adverse effects noted. Other comparisons were largely inconclusive. We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified. CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.