Central serous chorioretinopathy (CSCR) is a common retinal disorder that if persistent, recurrent, or chronic, can lead to permanent vision loss [1]. Although there have been considerable advances in recent years in our understanding of the anatomic characteristics and imaging features of the condition, the etiology and pathophysiology of the disorder remains incompletely understood. The waxing and waning nature of CSCR and the propensity of CSCR to spontaneously improve with resolution of subretinal fluid (SRF), is an important challenge in our ability to assess the efficacy of potential therapeutic interventions. Historically, thermal laser photocoagulation was used to treat cases with persistent fluid and vision loss [2]. The justification for applying this treatment was largely based on small case series, and not randomized clinical trial data. In addition, the pathophysiologic rationale for thermal laser was uncertain. Subsequently, verteporfin photodynamic therapy (PDT) applied using half-dose or half-fluence regimens was advocated as a potential therapeutic strategy based on a few small randomized trials [3]. PDT also appears to have a physiologic rationale, as treatment was associated with a reduction in choroidal thickness. However, as PDT is invasive, has potential side effects, and is expensive and not broadly available, there has been considerable interest in developing alternative therapeutics. Recently, the use of mineralocorticoid antagonists has gained interest as a potential simple, oral therapeutic for patients with CSCR. As mineralocorticoids are known to have an impact on the choroidal vasculature, the pathophysiologic rationale for using these agents would appear to be sound. Randomized clinical trial evidence to support the use of these agents, however, has been lacking, which underscores the importance of the recent paper by Lotery et al. describing the results of the VICI trial [4]. The VICI trial is a randomized, double-blind, placebocontrolled study to evaluate the efficacy of eplerenone for the treatment of active, previously untreated CSCR for more than four months. Patients were treated with eplerenone or placebo (when fluid was present) for a period of 12 months. Although over 400 subjects were initially evaluated for eligibility, ultimately only 114 were enrolled and randomly assigned. Despite this, the study was adequately powered to identify a 5-letter ETDRS distance visual acuity difference between the groups, which the authors deemed would be of clinical significance. The study had exceptionally good retention and strong adherence to protocol, which provides a high level of confidence in the results. Overall, the VICI study observed no significant benefit of eplerenone with regards to distance visual acuity (the primary outcome measure) or with respect to a number of key secondary anatomic outcomes including subretinal fluid and retinal thickness, resolution of fluid, and time to recurrence. To provide further context for their findings, the authors also performed a meta-analysis of other eplerenone trials and demonstrated relatively small and presumably clinically insignificant differences between eplerenone and placebo. The findings of the VICI trial are of substantial clinical relevance as they would not appear to support the continued use of eplerenone to treat these patients with active CSCR. Despite many strengths of this important trial, however, there are some issues, which warrant further analysis and review. First, choroidal neovascularization (CNV), particularly Type 1 or sub-retinal pigment epithelial (RPE) NV, is a known frequent complication and association of CSCR. The authors excluded CNV, but the methodology to exclude CNV is not specified. CNV can be difficult to identify on angiography in the setting of CSCR as it may be difficult to distinguish subtle leakage associated with Type 1 NV from staining of CSCR-related RPE alterations or “oozing” of dye from diffusely sick RPE. NV could contribute to * Srinivas R. Sadda ssadda@doheny.org

中文翻译：

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依普利酮治疗活动性中枢性浆液性脉络膜视网膜病变缺乏疗效

中央浆液性脉络膜视网膜病变 (CSCR) 是一种常见的视网膜疾病，如果持续、复发或慢性，可导致永久性视力丧失 [1]。尽管近年来我们对该病的解剖特征和影像学特征的理解取得了相当大的进展，但对该病的病因和病理生理学仍未完全了解。CSCR 的增减性质以及 CSCR 随着视网膜下液 (SRF) 的消退而自发改善的倾向，是我们评估潜在治疗干预效果的重要挑战。历史上，热激光光凝术用于治疗持续性液体和视力丧失的病例 [2]。应用这种治疗的理由主要基于小案例系列，而不是随机临床试验数据。此外，热激光的病理生理学原理尚不确定。随后，基于一些小型随机试验，提倡使用半剂量或半通量方案应用维替泊芬光动力疗法 (PDT) 作为潜在的治疗策略 [3]。PDT 似乎也有生理学原理，因为治疗与脉络膜厚度减少有关。然而，由于 PDT 是侵入性的，具有潜在的副作用，并且价格昂贵且无法广泛使用，因此人们对开发替代疗法产生了相当大的兴趣。最近，盐皮质激素拮抗剂作为 CSCR 患者潜在的简单口服治疗剂引起了人们的兴趣。由于已知盐皮质激素对脉络膜脉管系统有影响，使用这些药物的病理生理学原理似乎是合理的。然而，一直缺乏支持使用这些药物的随机临床试验证据，这强调了 Lotery 等人最近发表的论文的重要性。描述 VICI 试验的结果 [4]。VICI 试验是一项随机、双盲、安慰剂对照研究，旨在评估依普利酮治疗活性、先前未治疗的 CSCR 四个多月的疗效。患者接受依普利酮或安慰剂（当存在液体时）治疗 12 个月。尽管最初评估了 400 多名受试者的资格，但最终只有 114 名被纳入并随机分配。尽管如此，该研究有足够的效力来确定组之间 5 个字母的 ETDRS 远距离视力差异，作者认为这将具有临床意义。该研究具有非常好的保留性和对方案的强烈遵守，这为结果提供了高度的信心。总体而言，VICI 研究未观察到依普利酮在远视力（主要结果测量）或许多关键次要解剖结果（包括视网膜下液和视网膜厚度、液体分辨率和复发时间）方面的显着益处。为了为他们的发现提供进一步的背景，作者还对其他依普利酮试验进行了荟萃分析，并证明依普利酮和安慰剂之间的差异相对较小且可能临床上不显着。VICI 试验的结果具有重要的临床意义，因为它们似乎不支持继续使用依普利酮治疗这些患有活动性 CSCR 的患者。尽管这项重要试验有许多优势，但仍有一些问题需要进一步分析和审查。首先，脉络膜新生血管 (CNV)，特别是 1 型或视网膜下色素上皮 (RPE) NV，是已知的 CSCR 常见并发症和关联。作者排除了 CNV，但未指定排除 CNV 的方法。在 CSCR 的情况下，在血管造影上可能难以识别 CNV，因为可能难以区分与 1 型 NV 相关的细微渗漏与 CSCR 相关 RPE 改变的染色或来自弥漫性病变 RPE 的染料“渗出”。NV 可以为 * Srinivas R. Sadda ssadda@doheny.org 做出贡献 这需要进一步的分析和审查。首先，脉络膜新生血管 (CNV)，特别是 1 型或视网膜下色素上皮 (RPE) NV，是已知的 CSCR 常见并发症和关联。作者排除了 CNV，但未指定排除 CNV 的方法。在 CSCR 的情况下，在血管造影上可能难以识别 CNV，因为可能难以区分与 1 型 NV 相关的细微渗漏与 CSCR 相关 RPE 改变的染色或来自弥漫性病变 RPE 的染料“渗出”。NV 可以为 * Srinivas R. Sadda ssadda@doheny.org 做出贡献 这需要进一步的分析和审查。首先，脉络膜新生血管 (CNV)，特别是 1 型或视网膜下色素上皮 (RPE) NV，是已知的 CSCR 常见并发症和关联。作者排除了 CNV，但未指定排除 CNV 的方法。在 CSCR 的情况下，在血管造影上可能难以识别 CNV，因为可能难以区分与 1 型 NV 相关的细微渗漏与 CSCR 相关 RPE 改变的染色或来自弥漫性病变 RPE 的染料“渗出”。NV 可以为 * Srinivas R. Sadda ssadda@doheny.org 做出贡献 在 CSCR 的情况下，在血管造影上可能难以识别 CNV，因为可能难以区分与 1 型 NV 相关的细微渗漏与 CSCR 相关 RPE 改变的染色或来自弥漫性病变 RPE 的染料“渗出”。NV 可以为 * Srinivas R. Sadda ssadda@doheny.org 做出贡献 在 CSCR 的情况下，在血管造影上可能难以识别 CNV，因为可能难以区分与 1 型 NV 相关的细微渗漏与 CSCR 相关 RPE 改变的染色或来自弥漫性病变 RPE 的染料“渗出”。NV 可以为 * Srinivas R. Sadda ssadda@doheny.org 做出贡献