Eplerenone in the Treatment of Central Serous Chorioretinopathy
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Chatziralli et al. Int J Retin Vitr (2018) 4:33 https://doi.org/10.1186/s40942-018-0137-8 International Journal of Retina and Vitreous REVIEW Open Access Eplerenone in the treatment of central serous chorioretinopathy: a review of the literature Irini Chatziralli1* , Aikaterini Vlachodimitropoulou2, Chrysoula Daoula2, Christina Vrettou2, Eleni Galani2, George Theodossiadis1 and Panagiotis Theodossiadis1 Abstract Purpose: The purpose of this review is to examine the role of eplerenone in the treatment of central serous chori- oretinopathy (CSCR). Methods: A comprehensive search of the PubMed database has been conducted regarding eplerenone for CSCR, while studies using spironolactone were excluded. Articles and book chapters cited in the reference lists of articles obtained by this method were reviewed and included when considered appropriate, while the retrieved articles were fltered manually to exclude duplicates. Results: Oral eplerenone at a dose of 25–50 mg/day has been found to be efective and well-tolerated for the treat- ment of chronic CSCR. The published studies have shown signifcant improvement in visual acuity and decrease or total absorption of subretinal fuid in patients with CSCR treated with oral eplerenone. However, it should be noted that the majority of studies were retrospective with limited number of patients and short follow-up. On the other hand, patients presenting widespread retinal pigment epithelium changes are less likely to beneft from eplerenone treatment, which may argue for an earlier intervention. Conclusions: CSCR is a challenging disease to understand and treat, since its pathogenesis remains elusive and multifactorial. Pharmacologic approaches, like eplerenone, are intriguing, as they target several pathophysiological pathways and may lead to visual acuity improvement and more rapid recovery. Keywords: Central serous retinopathy, Eplerenone, Chronic, Mileralocorticoid Background metamorphopsia, changes in image size, decrease in con- Central serous chorioretinopathy (CSCR) is a chori- trast sensitivity, perception of blind spots or combina- oretinal disease, characterized by serous detachment tion of these symptoms [1]. Te diagnosis is performed of the neurosensory retina and/or retinal pigment epi- by dilated fundus exam and imaging of the retina and the thelium (RPE) with consequent accumulation of fuid choroid with optical coherence tomography, fuorescein [1–3]. In fact, the location and amount of fuid deter- angiography and indocyanine green angiography [4, 5]. mines the symptomatology in patients with CSCR. If CSCR is a common cause of visual impairment in the the fuid is located outside the macula, there may be no working-age population and has been estimated as the symptoms, while if the detachment afects the central fourth most frequently encountered non-surgical retin- macula, symptoms may include visual acuity decrease, opathy after age-related macular degeneration, diabetic retinopathy and retinal vein occlusion [1–3]. It typi- *Correspondence: [email protected] cally afects young to middle-aged men (30–50 years 1 2nd Department of Ophthalmology, National and Kapodistrian old), but patients with chronic disease (duration more University of Athens, 28, Papanastasiou Street, Agios Dimitrios, 17342 Athens, Greece than 6 months) may continue to sufer from the disease Full list of author information is available at the end of the article even in advanced age [1–3]. In a population-based study © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Chatziralli et al. Int J Retin Vitr (2018) 4:33 Page 2 of 5 conducted in Minnesota, the reported annual incidence of articles obtained by this method were reviewed of CSCR was 9.9 per 100,000 male cases compared to 1.7 and included when considered appropriate, while the per 100,000 women [6]. Apart from gender diferences, it retrieved articles were fltered manually to exclude seems that there is ethnic predilection with Asians pre- duplicates. senting higher incidence compared to other ethnic popu- lations [7]. Pathophysiology of CSCR and the “mineralocorticoid Although the exact pathogenesis of CSCR remains elu- receptor” theory sive, a number of risk factors for this disorder have been Te pathogenesis of CSCR is multifactorial and incom- implicated. High levels of endogenous (i.e., in Cushing’s pletely understood, making its treatment challenging. syndrome or in pregnancy) or exogenous (i.e., intra-artic- Te frst theory, proposed by Gass, suggested that there ular, intranasal, systemic or topical) corticosteroids, type is a focal choroidal hyper-permeability, leading to leak- A personality, obstructive sleep apnea, abnormal coagula- age of fuid into the subretinal space [15]. However, Mar- tion and platelet aggregation, infection with Helicobacter mor claimed that a focal disruption of the RPE could not pylori, male gender, pregnancy, smoking, hypertension, cause serous detachment owing to the ability of RPE cells antibiotic use, alcohol consumption and oxidative stress to compensate, and he proposed that CSCR is the result have been considered to be the most signifcant risk fac- of difuse metabolic impairment of the RPE [16]. In addi- tors for the development of CSCR [5, 8–10]. Moreover, tion, choroidal ischemia has been shown to be involved genetic susceptibility seems to play an important role in choroidal hyper-permeability and RPE dysfunction in the pathophysiology of CSCR and genetic polymor- [17]. phisms have been associated with CSCR [11–13]. Recently, signifcant progress has been made on the Te disease is usually idiopathic and often resolves understanding of the pathogenesis of CSCR, regarding spontaneously with visual recovery, although occasion- the molecular events triggering choroidal vasodilatation ally neurosensory retinal detachment persists or relapses in CSCR. Noticeably, CSCR is the only retinal disease and leads to permanent damage of the RPE and photo- involving fuid accumulation, which is not improved but receptors with subsequent visual impairment [1–3]. Cur- even worsened by corticosteroids [18]. Corticosteroids rent treatment modalities for CSCR generally target the include both glucocorticoid (cortisol) and mineralocor- RPE, choroid, or both. Tey aim to improve the ability ticoid (aldosterone), while receptors for glucocorticoid of the RPE to remove the subretinal fuid, to diminish and mineralocorticoid are expressed in Mueller cells and leakage from the choroidal vessels, or to decrease fuid choroidal vessels [18, 19]. Zhao et al. have found that sys- fux across the RPE barrier [4, 5]. Management usually temic and local glucocorticoids, which are known risk involves either waiting for spontaneous resolution, which factors for CSCR, act by binding both to the receptor commonly occurs within 3 months of onset, or the use of for glucocorticoid and that for mineralocorticoid with focal laser photocoagulation, photodynamic therapy with equally high afnity [20]. Additionally, Daruich et al. verteporfn and anti-vascular endothelial growth factor proposed that over activation of the MR in the choroidal (anti-VEGF) agents in cases of choroidal neovasculari- endothelial cells induces upregulation of the vasodila- zation related to CSCR [4]. Recently, mineralocorticoid tor potassium channel KCa2.3, which modulates smooth receptors (MR) have been implicated in the pathophysi- muscle cells relaxation in the choroidal vasculature [21, ology of CSCR; therefore, factors targeting these recep- 22]. Tis process has been shown to cause choroidal tors may be used for the treatment of CSCR [14]. In light vasodilation, fuid accumulation in the retina, and to of the above, the purpose of this review is to examine the promote retinal neovascularization in hypoxic condi- role of eplerenone, an MR antagonist, in the treatment of tions [18]. Terefore, this link between corticosteroids CSCR. and CSCR, combined with the observation of an induced CSCR-like model in the rat following MR pathway acti- Literature search vation, has prompted the evaluation of MR antagonist in We conducted a comprehensive search of the PubMed the treatment of CSCR [14]. database to include articles up to December 31th, 2017, using the following search algorithm: (central serous Eplerenone in the treatment of CSCR retinopathy OR central serous chorioretinopathy) AND Eplerenone is an MR antagonist with an increased MR (eplerenone OR mineralocorticoid). Only studies or selectivity and higher afnity compared to spironol- cases series evaluating patients with CSCR treated with actone. However, eplerenone has about 10- to 20- fold eplerenone were included in this review, while studies lower binding to progesterone and androgen receptors regarding treatment with spironolactone were excluded. and does not include the hormonal efects to the same Articles and book chapters cited in the reference lists extent, thereby limiting sex-hormone-related adverse Chatziralli Table 1 Characteristics and results of studies evaluating oral eplerenone