Scientific Papers

Real-world practice patterns of eplerenone use for central serous chorioretinopathy | International Journal of Retina and Vitreous

This survey compiled the experiences of retina specialists from around the world and India regarding CSCR management including the use of eplerenone. The survey revealed that approximately 62% of retina specialists were familiar with oral eplerenone therapy for the treatment of CSCR. In terms of eplerenone usage, preferred cases, preferred time for treating, dosage and duration of treatment, satisfaction with treatment, and eplerenone side effects, we observed significant differences between retina specialists from India and those from other regions of the world. The survey revealed that CSCR is a common retinal pathology, with more than 50% of respondents observing up to ten new cases per month, including both acute and chronic forms of the disease. The average experience of survey respondents was approximately 15 years, making the survey’s findings credible, significant, and pertinent.

In ophthalmology, PDT with verteporfin has a wide range of indications, including central serous chorioretinopathy [3, 23, 24]. PDT is an effective treatment for CSCR regarding the rate of SRF reabsorption, particularly in cases of acute CSCR with sub/juxta foveal leaks, recurrent CSCR, and chronic CSCR [23, 24]. Due to its wide applicability and efficacy in different stages of CSCR, PDT is either the primary treatment or considered a major treatment option in the management of CSCR, although its exact mechanisms of action remains unclear [1, 3]. Particularly, the long term effect of repeated PDT on RPE cells from complex CSCR [25] remains to be evaluated since verteporfin PDT, even when used at half fluence or half dose was shown to cause histological damages to RPE cells [26, 27].

Since July 2021, there has been a global shortage of verteporfin (Visudyne®), an essential drug required for PDT. The shortage of verteporfin has had a significant impact on the care of ophthalmic patients around the world, and may have resulted in significant and irreversible vision loss, as well as the need to consider alternatives to PDT [28]. In our survey, we found that only 12% of retina specialists were able to access Visudyne® and perform PDT on CSCR patients without difficulty. 63% of the 149 retinal specialists surveyed who had experience using eplerenone did not have access to photodynamic therapy (PDT), and another 30% found it difficult to obtain the drug. Only 7% of respondents who were using eplerenone also had easy access to PDT. In comparison to respondents from the rest of the world, those from India had more experience using eplerenone in CSCR management and had no access to verteporfin and PDT. Thus, the non-availability of PDT in countries such as India may have compelled clinicians to seek alternative therapy for CSCR management, and eplerenone has emerged as a viable alternative to PDT for CSCR management.

An important and exciting finding from this survey was that approximately 58% (86/149) of respondents used eplerenone in chronic cases of CSCR, while only 15% used it in acute cases of CSCR. The acute form of CSCR is caused by increased choroidal vascular permeability, which results in focal changes in the RPE, such as RPE detachment, followed by a micro RPE rip and fluid accumulation in the neurosensory space. In contrast, the chronic form of CSCR is characterized by diffuse rather than focal RPE abnormalities, resulting in dysfunctional RPE and persistent subretinal fluid [29]. During systemic corticosteroid treatment, RPE and choriocapillaris receptor reactivity may reveal the strong association between steroid use and CSCR [30]. Daruich et al. hypothesized that excessive activation of the mineralocorticoid receptor in the choroidal endothelial cells by aldosterone or glucocorticoids induces upregulation of the vasodilator potassium channel KCa2.3, which modulates smooth muscle relaxation in the choroidal vessels. In addition, mineralocorticoid receptor activation in human RPE cells derived from induced pluripotent stem cells showed deregulation of genes involved in RPE barrier integrity, transcellular transport and choroid functions [8], supporting the use of mineralocorticoid antagonists in the treatment of acute CSCR [31]. Similarly, a recent study published by our group on the effects of oral eplerenone therapy in acute cases of CSCR found faster SRF resolution, rapid improvement in visual acuity, fewer recurrences in the affected eye, a lower risk of developing CSCR in the contralateral eye, and fewer ocular and systemic side effects [12]. The addition of oral eplerenone therapy to lifestyle modifications in acute cases of CSCR could expedite the resolution of SRF, prevent long-term RPE damage, and improve visual outcomes.

Animal models in which mineralocorticoid receptor is activated either by chronic aldosterone exposure or by overexpression of the human receptor show a pachychoroid-like phenotype, suggesting that mineralocorticoid pathway activation may favour choroidal pathology [7] which may indicate that MR antagonists could have a long term effect on the pachychoroid phenotype, which has not been yet evaluated. Indeed, all studies on CSCR evaluate as the main endpoint, the resolution of subretinal fluid, and not the underlying mechanisms causing this sign.

A large-scale, multicentre, randomised VICI trial evaluating the efficacy of eplerenone in patients with persistent CSCR failed to demonstrate a superior beneficial response to placebo [13]. The VICI trial was a randomized, double-blind, multicentre, placebo-controlled study from the United Kingdom that was designed to assess the efficacy of eplerenone in the treatment of active, previously untreated CSCR for more than four months [13]. Patients were administered eplerenone or a placebo (when fluid was present) for 12 months. Improvement in visual acuity was the primary outcome measure. The results of the study suggested that eplerenone therapy was not superior to placebo in the treatment of persistent CSCR. According to the findings of this survey, the results of the VICI trial did influence the treatment practices of retina specialists in the management of CSCR. 44% (42/95) of retina specialists from India and 69% (37/54) of retina specialists from the rest of the world confirmed in the survey that the results of the VICI trial had an impact on their CSCR management practices. This observation was supported by statistical evidence. The absence of PDT in clinical practice in India may have been the most likely explanation for why the VICI trial results had less of an impact on Indian retinal specialists than on their counterparts in the rest of the world. Consequently, Indian retina specialists view oral eplerenone as a viable alternative to PDT.

All respondents to the current survey administered eplerenone to CSCR patients at starting doses ranging from 25 to 50 mg per day and for a variable period of time. Even in the recently published prospective VICI trial, eplerenone therapy was discontinued upon complete resolution of SRF or if the patient’s potassium levels increased. There was no established dosage protocol for eplerenone use in CSCR. But in other diseases in which eplerenone or other MR antagonists are approved, the drugs were shown to act of tissue remodelling and play a role as disease modifying drugs.

Compared to retina specialists from other countries, retina specialists from India used a much lower starting dose of 25 mg per day. In cases of CSCR, a lower starting dose of eplerenone may have been administered out of concern for systemic side effects. However, there were no significant differences between the side effect profiles reported by Indian retina specialists and their counterparts from the rest of the world after CSCR treatment with eplerenone. The levels of treatment satisfaction among retinal specialists from the two distinct geographic regions were also significantly distinct. Compared to their Indian counterparts, retinal specialists from countries other than India experience poor satisfaction levels following eplerenone treatment.

One of the most significant limitations is the size of the survey’s sample. The number of retina specialists who participated in this survey was disproportionately small compared to the total number of retina specialists in the world. A minimum sample size was required to ensure the validity of the study and analysis. The primary advantage of this paper is that it provides first-hand accounts of the observations made by clinicians following the use of eplerenone in the management of CSCR.

In conclusion, the treatment of CSCR varies across the globe and is primarily influenced by the availability of PDT and the results of an established clinical trial such as the VICI trial. In spite of limited benefit of eplerenone reported by VICI trial, eplerenone use is continued as supported by real-life experience.

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