Effectiveness of Spironolactone for Central Serous Chorioretinopathy
Spironolactone demonstrates moderate effectiveness for central serous chorioretinopathy (CSC), with the strongest evidence supporting its use in acute CSC where it achieves significantly faster subretinal fluid resolution compared to observation alone, though evidence remains limited by the lack of large randomized controlled trials. 1
Evidence Quality and Strength
The evidence base for spironolactone in CSC consists primarily of small prospective studies and retrospective case series, with only one adequately powered randomized controlled trial available. 1 This contrasts sharply with eplerenone (another mineralocorticoid receptor antagonist), which has been evaluated in two large RCTs (SPECTRA and VICI trials) that showed no benefit over placebo or photodynamic therapy. 1 The absence of similar large-scale trials for spironolactone represents a critical evidence gap.
Acute CSC: Best Available Evidence
For acute CSC, spironolactone 40 mg twice daily for 2 months achieves complete subretinal fluid resolution in 56% of patients versus only 8% with observation (p=0.018). 1, 2 This represents the highest quality evidence available from a prospective randomized controlled trial by Sun et al. 1
Treatment Outcomes in Acute CSC:
- Complete fluid resolution: 56% at 2 months with treatment versus 8% without (statistically significant) 1, 2
- Visual acuity improvement: Mean LogMAR improved from 0.25 to 0.05 1
- Central macular thickness: Significantly greater reduction compared to observation 2
- Subfoveal choroidal thickness: Decreased from 502.50±87.38 μm to 427.44±74.37 μm at 2 months 2
Chronic CSC: More Limited Evidence
For chronic CSC, the evidence is weaker, consisting primarily of uncontrolled prospective case series and retrospective studies. 1
Treatment Outcomes in Chronic CSC:
- Complete fluid resolution rates: Range from 25% to 71% across studies, with most reporting 44-69% 1
- Visual improvement: Mean LogMAR BCVA improved from 0.54 to 0.42 (p=0.04) in one prospective series 1, 3
- Duration of treatment: Typically 6 weeks to 4 months, with dosing adjusted based on response 1
A critical limitation is that 71% "improvement or resolution" reported in some studies conflates partial response with complete resolution, making interpretation difficult. 1
Comparative Effectiveness
When compared head-to-head with half-dose photodynamic therapy (PDT) in chronic CSC, spironolactone showed similar complete resolution rates at 12 months (69% versus 88%, not statistically significant), but significantly higher recurrence rates (p=0.002), suggesting PDT has more durable effects on the dysfunctional choroid. 1
When compared to conservative treatment (vitamins/tranquilizers), spironolactone achieved 57% complete resolution versus 32% (p=0.032), though baseline visual acuity was worse in the spironolactone group. 1
Dosing Regimens
Start with 25 mg twice daily (50 mg total daily) for most CSC patients. 1 Some protocols use:
- Acute CSC: 40 mg twice daily for 2 months 1, 2
- Chronic CSC: 25 mg daily initially, increasing to 25 mg twice daily if incomplete response after 6 weeks 1, 3
- Treatment duration: Minimum 6 weeks, typically 2-4 months depending on response 1
Critical Safety Monitoring
Check serum potassium and creatinine within 2-4 weeks of initiation, then monthly during treatment. 4 This is non-negotiable given the risk of life-threatening hyperkalemia and cardiac arrest. 1, 5
Absolute Contraindications:
- Serum potassium >5.0-5.5 mEq/L at baseline 4
- Concurrent use of potassium supplements or other potassium-sparing diuretics 1, 5
- Potent CYP3A4 inhibitors 1, 5
- Combined use of ACE inhibitor plus ARB (significantly increases hyperkalemia risk) 1, 4, 5
- eGFR <25-30 mL/min/1.73 m² 4
High-Risk Populations Requiring Closer Monitoring:
Common Side Effects (>10% of patients):
Special Clinical Scenarios
For steroid-induced CSC, spironolactone achieved 82% complete resolution when systemic steroids were discontinued concurrently. 1 This represents one of the highest success rates reported, though the confounding effect of steroid discontinuation makes interpretation challenging. 1
For bullous variant CSC (a severe presentation), case reports suggest spironolactone 50 mg daily can achieve resolution within 2 months. 6
Critical Limitations and Caveats
The apparent benefits of spironolactone must be interpreted cautiously because acute CSC spontaneously resolves in many cases, and even chronic CSC resolves spontaneously in up to 30% of untreated patients. 1 This natural history makes uncontrolled studies particularly difficult to interpret.
The lack of large, adequately powered RCTs comparable to those conducted for eplerenone (which showed no benefit) raises questions about whether spironolactone's apparent effectiveness in smaller studies reflects true efficacy or publication bias and natural disease course. 1
Recurrence rates appear higher with spironolactone compared to PDT, suggesting it may be better suited as initial therapy for acute cases rather than definitive treatment for chronic disease. 1
Practical Treatment Algorithm
For acute CSC (<3 months duration):
- Verify potassium <5.0 mEq/L and no contraindications 4
- Start spironolactone 40 mg twice daily 1, 2
- Recheck potassium and creatinine at 2 weeks 4
- Continue for 2 months with monthly potassium monitoring 4
- Expect 56% complete resolution versus 8% with observation 1, 2
For chronic CSC (>3 months duration):
- Consider that evidence is weaker than for acute CSC 1
- Start 25 mg twice daily 1
- Recheck potassium at 2 weeks, then monthly 4
- If incomplete response at 6 weeks, continue for total of 3-4 months 1
- Expect 44-69% complete resolution, but higher recurrence risk than PDT 1
- Consider half-dose PDT as alternative given lower recurrence rates 1