Salehi Mahsa, Wenick Adam S, Law Hua Andrew, Evans Jennifer R, Gehlbach Peter
Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Cochrane Database Syst Rev. 2015 Dec 22;2015(12):CD011841. doi: 10.1002/14651858.CD011841.pub2.
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.
AUTHORS' CONCLUSIONS: 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.
中心性浆液性脉络膜视网膜病变(CSC)的特征是神经视网膜浆液性脱离,伴有脉络膜和视网膜色素上皮(RPE)功能障碍。视网膜的影响通常是自限性的,尽管有些人由于进行性和永久性光感受器损伤或RPE萎缩而导致不可逆的视力丧失。CSC有多种干预措施,包括但不限于激光治疗、光动力疗法(PDT)和玻璃体内注射抗血管内皮生长因子(抗VEGF)药物。然而,尚不清楚这些治疗或其他治疗是否比观察或其他干预措施具有显著优势。目前,对于CSC的管理尚无基于证据的共识。很大程度上由于CSC有自发缓解或呈反复波动病程的倾向,最常见的初始治疗方法是观察。目前尚不清楚这在安全性和有效性方面是否是最佳方法。
比较中心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Cochrane中心对照试验注册库(CENTRAL)(2015年第9期,其中包含Cochrane眼科和视力试验注册库)、Ovid MEDLINE、Ovid MEDLINE在研及其他未索引引文、Ovid MEDLINE每日更新、Ovid OLDMEDLINE(1946年1月至2014年2月)、EMBASE(1980年1月至2015年10月)、ISRCTN注册库(www.isrctn.com/editAdvancedSearch)、ClinicalTrials.gov(www.clinicaltrials.gov)以及世界卫生组织(WHO)国际临床试验注册平台(ICTRP)(www.who.int/ictrp/search/en)。我们在电子检索试验时未使用任何日期或语言限制。我们最后一次检索电子数据库的时间是2015年10月5日。
比较CSC的任何干预措施与CSC的任何其他干预措施或对照的随机对照试验(RCT)。
两名综述作者独立选择研究并提取数据。我们使用固定效应模型汇总所有研究的数据。对于应用于眼部的干预措施(即非全身干预措施),我们在网络荟萃分析模型中综合直接和间接证据。
我们纳入了25项研究,共1098名参与者(1098只眼),随访时间为16周至12年。研究在欧洲、南北美洲、中东和亚洲进行。这些试验规模较小(大多数试验纳入的参与者少于50名)且报告质量较差;通常不清楚试验的关键方面,如分配隐藏是否实施。相当一部分试验未采用盲法。这些研究考虑了多种治疗方法:抗VEGF(雷珠单抗、贝伐单抗)、PDT(全剂量、半剂量、30%、低能量)、激光治疗(氩激光、氪激光和微脉冲激光)、β受体阻滞剂、碳酸酐酶抑制剂、幽门螺杆菌治疗以及营养补充剂(Icaps、叶黄素);每次比较仅有一两项试验提供数据。由于研究局限性和估计不精确,我们对大多数分析的偏倚风险和不精确性进行了降级。由于缺乏试验以及传递性问题,特别是在急性或慢性CSC方面,网络荟萃分析(如我们方案中所计划)无助于解决这种不确定性。两项试验的低质量证据表明,在急性CSC中,抗VEGF(雷珠单抗或贝伐单抗)或观察对6个月时视力变化的影响差异不大(平均差(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)。所有参与者在6个月时CSC均已缓解。未观察到显著不良反应。一项研究(58名参与者)的低质量证据表明,与假治疗相比,如果对急性CSC采用半剂量PDT治疗,可能在12个月时视力有小幅改善(MD -0.10 logMAR,95% CI -0.18至-0.02),复发率较低(风险比(RR)0.10,95% CI 0.01至0.81),持续性CSC较少(RR 0.12,95% CI 0.01至-1.02)。未观察到显著不良事件。两项试验(56名参与者)在慢性CSC中比较抗VEGF与低能量PDT,未发现12个月时视力有任何差异的证据(MD 0.03 logMAR,95% CI -0.08至0.15)。有一些证据表明,与接受PDT治疗的人相比,抗VEGF组中更多人出现CSC复发,但由于试验之间存在不一致性,难以估计其效应。抗VEGF组中更多人在12个月时存在持续性CSC(RR 6.19,95% CI 1.61至23.81;34名参与者)。两项关于微脉冲激光的小型试验,一项针对急性CSC患者,一项针对慢性CSC患者,提供了低质量证据表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)。未观察到显著不良反应。其他比较大多无定论。我们确定了12项正在进行的试验,涵盖以下干预措施:急性CSC中的阿柏西普和依普利酮;慢性CSC中的螺内酯、依普利酮、叶黄素、PDT和微脉冲激光;以及两项试验中的微脉冲激光和口服米非司酮,试验中CSC类型未明确指定。
CSC在很大程度上仍然是一种难以捉摸的疾病,这一方面是由于很大一部分人有自然改善的病史,另一方面是因为在已发表的RCT中,没有单一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、研究的实施以及纳入和随访至揭示终点的参与者相对较少,限制了现有数据的实用性。对于通常作为其自然病史一部分而自发缓解的急性CSC进行治疗是否具有临床重要益处尚不清楚。将个体治疗与自然病史进行比较的RCT对于确定进行直接比较的潜在治疗组将是有价值的。在迄今为止研究的干预措施中,PDT或微脉冲激光治疗在未来试验中似乎最有前景。