Eplerenone and Spironolactone for Chronic Central Serous Chorioretinopathy: A Systematic Review and Meta-Analysis

To evaluate the efficacy and safety of mineralocorticoid receptor antagonists (MRAs), specifically eplerenone and spironolactone, in comparison to observation, photodynamic therapy (PDT), and subthreshold micropulse laser (SML) for chronic central serous chorioretinopathy (cCSCR).

In the context of cCSCR, MRAs are thought to reduce choroidal vascular hyperpermeability and thickness by inhibiting the mineralocorticoid receptor pathways that contribute to fluid accumulation.

A systematic literature search was performed using Ovid MEDLINE, Embase, and the Cochrane Library from January 2000 to March 2024 for comparative studies evaluating the efficacy of MRAs against other treatment arms for cCSCR. The primary outcome was the best-corrected visual acuity (BCVA) at the last study visit, as well as at specific follow-up timepoints (ie, 1 month, 3 months, 6 months, 12 months). Secondary outcomes included retinal thickness (RT), subretinal fluid (SRF) height, and SRF resolution at the same timepoints. Meta-analyses were performed using a random-effects model, with subgroup analyses performed for eplerenone and spironolactone separately. A P-value of less than 0.05 was considered statistically significant.

Thirteen articles (four RCTs reporting on 253 eyes and nine observational studies reporting on 393 eyes, mean follow-up duration = 7.02 ± 3.78 months) were included. The mean BCVA at the last study visit was similar between the MRA and observation groups (WMD=-0.01 logMAR, 95% CI = [-0.05, 0.02], P = .40, n = 5 studies). However, MRAs resulted in a significantly lower mean SRF height at 1 month (WMD=-69.56 µm, 95% CI [-127.26, -11.86], P = .02, n = 2 studies), while the observation group had a significantly lower SRF height at 12 months (WMD=48.23 µm, 95% CI [45.99, 50.46], P < .00001, n = 2 studies). Similarly, MRAs demonstrated a higher rate of SRF resolution at 1 month (RR=4.24, 95% CI = [1.54, 11.72], P = .005), whereas the observation group showed a higher resolution rate at 12 months (RR=0.45, 95% CI = [0.22, 0.95], P = .04). On subgroup analysis, spironolactone showed a significantly reduced mean RT at the last study visit compared to observation (WMD = -46.44 µm, 95% CI [-74.76, -18.13], P = .001, n = 2 studies). When compared to PDT, MRAs were associated with a significantly higher mean SRF height at the last study visit (WMD = 51.99 µm, 95% CI [2.70, 101.27], P = .04, n = 2 studies). In contrast, efficacy outcomes were largely similar between patients treated with MRAs and SML at the last study visit, with no significant differences in SRF resolution (P = .22, n = 2 studies).

MRAs offer short-term benefits in reducing SRF but may have limited long-term durability based on current evidence, highlighting the need for further studies.