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A meta-analysis comparing mineralocorticoid receptor (MR) antagonists (eplerenone or spironolactone) versus observation or placebo in the treatment of central serous chorioretinopathy (CSCR) based on best-corrected visual acuity (BCVA) and subretinal fluid (SRF) level data from randomized controlled trials (RCTs).Central serous chorioretinopathy patients may demonstrate decreased visual acuity, reduced contrast sensitivity, scotomas, and metamorphopsia. Although multiple treatment options for CSCR have been proposed, compelling evidence for any particular method is still lacking.Three databases (PubMed, EMBASE, and BIOSIS) were searched for potentially relevant records as of March 2018. Of 114 unique studies identified, 5 RCTs comparing BCVA with either eplerenone or spironolactone versus observation or placebo were included. The quality of articles was assessed according to the Cochrane Risk of Bias Tool, with any discrepancies resolved by author consensus.A total of 145 eyes of patients with CSCR were included in the meta-analysis. Compared with placebo or observation, MR antagonist treatment showed a significant positive effect on BCVA after both 1 month (weighted mean difference [WMD], -0.05 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.07 to -0.02 logMAR; Z = 3.94; P0.0001) and 2 months (WMD, -0.10 logMAR; 95% CI, -0.14 to -0.06 logMAR; Z = 4.69; P0.00001). Mineralocorticoid receptor antagonist treatment also significantly reduced SRF height in CSCR at 1 month (WMD, -81.15 μm; 95% CI, -148.25 to -14.05 μm; Z = 2.37; P = 0.02). However, this effect was no longer significant at 2 months (WMD, -58.63 μm; 95% CI, -155.40 to 38.13 μm; Z = 1.19; P = 0.23). None of the patients in the 5 trials withdrew because of adverse effects, and blood electrolyte levels, including potassium, remained normal in all cases.Our findings suggest a modest benefit with MR antagonist therapy for CSCR patients in improving BCVA. We anticipate that MR antagonists will be well tolerated by most CSCR patients and that barriers to starting a trial of these medications in nonresolving CSCR should be low.

Rationale: Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective: Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results: We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions: Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies.