Eplerenon as Adjunctive Therapy for Choroidal Neovascularisation with Serous Pigment

Serous pigment epithelial retinal detachment (sPED) is sharply demarcated, smooth, dome shaped elevation of retinal pigment epithelium (RPE) [1]. SPEDs are manifestation of neovascular age related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSR). Controversy remains about etiology of sPEDs [2-5]. The over activation of the mineralocorticoid receptor (MR) pathway has been shown to cause fluid accumulation in the retina, choroidal vasodilation, and to promote retinal neovascularization in hypoxic conditions [1-4,6-8]. According the role of mineralcorticosteroid receptors in retina, eplerenon has shown beneficial effect in treatment of CSR [5].

A well-known complication of PED is a RPE tear caused by contraction of the elevated PED and retraction of RPE resulting in absence of RPE underneath the neurosensory retina [5,6]. RPE rip could be serious vision threating complication of laser photocoagulation, photodynamic therapy and anti-VEGF therapy. There is an evidence that sPED with height > 350 ɥm are more high risk for development of RPE and consecutive macular atrophy [7]. Anti VEGF is nowdays the main therapeutic approach for nAMD and despite chronic presence of sPED and subretinal fluid in regular and continuous anti-VEGF regimes have comparable and benefitial effect in visual and functional outcome [8]. Due to the costs of antiVEGF and patient compliance with intravitreal injections alternative treatments are rational approach to those cases [5]. treated with three initially consecutive intravitreal injections of 2 mg aflibercept (EYLEA®) in private practice. After 6 weeks after last intravitreal aflibercept therapy per oral Eplerenon 50 mg (INSPRA®) once daily was prescribed as persistent sPED exists and relatively large collection of subretinal fluid (>50 ɥm) presented in macular region. Both patients are females, age of 71 and 64. Visual acuity baseline 30 ETDRS (Early treatement diabetic retinopathy) letters.
After 12 weeks of last treatment with anti VEGF and 6 weeks after Eplerenon prescription visual acuity was 70 and 75 ETDRS letters respectively. Intraocular pressure was with normal limits during all controls (less than 21 mmHg). Both patients had detailed ophthalomologic examination on all consecutive visits. It included complete anterior segment of the eye exam which was within normal limits in both cases. Fundoscopic exam in mydriatic conditions show soft drusen on both eyes, complete resolution of the blood on eplerenon baseline visit and no blood on consecutive visit in treated eye. Both patients had incomplete posterior vitreous detachment, no vitreoretinal changes. Fellow eye has high risk AMD in younger patient (presence of large soft drusen in macula). In other patient fellow eye has soft drusen and occult juxtafoveal CNV. Both patient were treatment naive. a) 6 weeks after 3rd injection of aflibercept treatment.

b)
6 weeks after adjunctive 50 mg eplerenon treatment. Both patients were previously for 5 years treated with oral beta blockers (metoprolol 25 mg once daily) and ACE inhibitors (enalapril 10 mg twice daily) for arterial hypertension and received statins (atorvastatin 10 mg once daily) for regulation of hyperlipoproteinemia type IIa. Other systemic and ocular health problems were not present. Both patients presented type A personality. Central retinal thickness and central sPED height measured 6 weeks after eplerenon 50 mg treatment and 12 weeks after last intravitreal injection of 2 mg aflibercept seemed to be evidently reduced. Visual acuity during treatment with Your next submission with Juniper Publishers will reach you the below assets • Unceasing customer service Track the below URL for one-step submission https://juniperpublishers.com/online-submission.php eplerenon 50 mg was stable through 6 weeks 70 and 75 ETDRS letters respectively. Both patients are educated for self testing Amsler grid, and Amsler grid tests performance was stable and unchanged during all follow up period. Potassium plasma level was monthly monitored in both patients (within normal limits <4,1 mmol/L). Younger patient is now switched to pro re nata (PRN) anti VEGF therapeutic regime, as signs of CNV activity in both cases considered are visual acuity, Amsler grid test, signs of hemorrhage on clinical exam, increase in retinal thickness due to the intraretinal edema on OCT (Figure 1). Other patient refuse further antiVEGF treatment and she is still taking eplerenon combined with antioxidant and vitamin supplements.

Discussion
The purpose of this case presentation is to show effect of eplerenone, a mineralocorticoid receptor antagonist, as a treatment option for reduction of SRF and sPED in cases with nAMD. The role of mineral corticosteroid receptors (MR) in retinal disorders is emerging and the potential association with physiological traits are investigated in CNV. The place of MR antagonists for retinal diseases treatment are discussed [1][2][3][4].
Central subfield thickness at follow-up visit after eplerenon initiation significantly decreased more than 10% from baseline which was previously reported in cases with chronic CSR [5]. Following therapy with eplerenon, there was a significant reduction in SF, reduction in CST, and improvement visual acuity in eyes with chronic CSR [5]. A majority of eyes with CSR presented by Singh and al [5] (47.1%) demonstrated stable SRF on treatment, while 35.3% had complete resolution of SRF. Results of this study indicate that eplerenone could be beneficial in the treatment of unresolved CSR. Considering that some cases in nAMD morphologically reminds on CSR could be rational approach to treat those patients with mineralcorticosteroid antagonists with the goal of serous transudation reduction and to reduce number of intravitreal injections which could be serious burden for patients. Also, presence of subretinal and sub RPE fluid is still not mandatory indication for continuous and strict anti VEGF regime. There are evidences that antiVEGF therapy in cases with large serous PED are prone to RPE rip [7,8]. As it is still controversial, there could be some benefit of anatgonists of mineralcorticosteroid receptors in some cases with resistent and non compliant patients with sPED. Further more precise conclusions and role of mineralcorticosteroid receptors in nAMD request more controlled and precise clinical investigations.