What is the role of Eplerenone (a mineralocorticoid receptor antagonist) in the treatment of central serous chorioretinopathy (CSC)?

Role of Eplerenone in Treatment of Central Serous Chorioretinopathy

Eplerenone should NOT be used as first-line treatment for chronic central serous chorioretinopathy (CSC) based on the highest quality evidence from large randomized controlled trials showing no superiority over placebo. 1

Current Evidence-Based Recommendation

The 2020 VICI trial—the largest and most rigorous randomized, double-blind, placebo-controlled study to date—definitively demonstrated that eplerenone (50 mg daily for 12 months) provided no significant improvement in visual acuity compared to placebo in 114 patients with chronic CSC. 1 The adjusted mean difference was only 1.73 letters (95% CI -1.12 to 4.57; p=0.24), which is not clinically meaningful. 1

The 2024 evidence-based treatment guideline explicitly states that large RCTs found only 16-17% of eplerenone-treated patients achieved complete subretinal fluid resolution, and current evidence from these trials does not support the notion that patients with chronic CSC benefit from mineralocorticoid receptor antagonist treatment. 2

When Eplerenone May Be Considered

Eplerenone can be considered as a second-line or salvage therapy in the following specific circumstances:

Patient Selection Criteria

• After failure of half-dose photodynamic therapy (PDT), which remains the most effective first-line treatment with 51-67% complete subretinal fluid resolution rates 2
• When PDT is unavailable or cost-prohibitive at the treatment center 2
• Patients with focal leakage point on ICGA and absence of choroidal neovascularization on OCT angiography, as these are predictive factors for better response 2
• Avoid in patients with widespread RPE changes, as they benefit less from eplerenone 2

Dosing Protocol

Initial Assessment:

• Do not initiate if serum potassium >5.5 mEq/L or creatinine clearance ≤30 mL/min 2
• Check baseline serum potassium and creatinine levels 2

Dosing Schedule:

• Start with 25 mg daily 2
• Recheck potassium after 1 week 2
• If potassium <5.0 mEq/L, increase to 50 mg daily 2
• If potassium 5.0-5.4 mEq/L, maintain current dose 2
• If potassium 5.5-5.9 mEq/L, reduce dose (50 mg to 25 mg daily, or 25 mg daily to every other day) 2
• If potassium ≥6.0 mEq/L, stop immediately and restart only when <5.5 mEq/L 2

Monitoring:

• Check serum potassium monthly and adjust dosing accordingly 2

Expected Outcomes and Timeline

When eplerenone does work, effects should be evident within a few months, though the exact timeline is poorly defined. 2 Retrospective studies (lower quality evidence) reported 29% complete subretinal fluid resolution in patients who failed other treatments after a median of 106 days. 2 However, these retrospective findings conflict sharply with the prospective RCT data showing minimal benefit. 1

Safety Profile and Contraindications

Common Side Effects (up to 10% of patients): 2

• Nausea
• Diarrhea
• Dizziness
• Headache

Absolute Contraindications: 2

• Potassium supplements
• Potassium-sparing diuretics
• Potent CYP3A4 inhibitors
• Combined ACE inhibitor and angiotensin receptor blocker therapy

Serious Adverse Events:

• Hyperkalemia occurred in 14% of patients in the VICI trial 1

Why Eplerenone Over Spironolactone

If a mineralocorticoid receptor antagonist is chosen, eplerenone is preferred over spironolactone, particularly in male patients, because it is far less likely to cause gynecomastia and mastalgia due to its more selective receptor binding. 2 The cost difference is now negligible after patent expiration. 2

Critical Clinical Pitfalls

Do not prescribe eplerenone as first-line therapy. The 2020 VICI trial authors explicitly stated: "Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice." 1 This represents the highest quality evidence available and directly contradicts earlier retrospective studies and pilot trials that suggested benefit. 2

The evidence divergence is stark: Earlier retrospective studies from 2013-2018 reported 20-66% resolution rates 2, but the 2020 prospective RCT showed no benefit over placebo 1, and the 2024 guideline update reinforced that large RCTs do not support MRA use. 2

Preferred Treatment Algorithm

1. First-line: Half-dose or half-fluence PDT (most effective with 51-67% resolution) 2
2. Second-line (if PDT unavailable/failed): Consider focal laser for eccentric leakage, high-density subthreshold micropulse laser, or eplerenone on case-by-case basis 2
3. Salvage therapy: Eplerenone may be attempted in PDT-refractory cases with favorable imaging characteristics (focal ICGA leakage, no CNV, minimal RPE changes) 2