Residency · Residency · Ophthalmology

Central Serous Chorioretinopathy

Pathophysiology

Central serous chorioretinopathy is fundamentally a disorder of the choroid and retinal pigment epithelium, not a primary retinal vascular disease. The primary abnormality is choroidal hyperpermeability and congestion -- a thickened, engorged choroid (pachychoroid) generates increased hydrostatic pressure that overwhelms the barrier function of the RPE. At sites of focal RPE dysfunction, fluid leaks through the RPE into the subretinal space, producing a neurosensory retinal detachment.

Pachychoroid Spectrum

CSC belongs to a continuum of diseases united by the pachychoroid phenotype. This spectrum ranges from pachychoroid pigment epitheliopathy (PPE), in which choroidal thickening produces RPE changes without fluid, through CSC with frank subretinal fluid, to pachychoroid neovasculopathy (PNV) and polypoidal choroidal vasculopathy (PCV), in which the pachychoroid drives neovascularization. The common feature across this spectrum is a thickened choroid with dilated Haller layer vessels -- called pachyvessels -- and attenuation of the overlying choriocapillaris.

Epidemiology and Risk Factors

CSC has a strong male predominance, with male-to-female ratios ranging from 6:1 to 10:1. It typically affects patients between the ages of 20 and 50, with a peak incidence in the 30s and 40s. Corticosteroid use is the strongest modifiable risk factor, and all routes of administration -- systemic, inhaled, topical, epidural, and nasal -- can precipitate or worsen the disease. Other risk factors include Type A personality and psychological stress, pregnancy (especially in the third trimester, with typical postpartum resolution), Cushing syndrome and other states of endogenous hypercortisolism, obstructive sleep apnea, Helicobacter pylori infection (though this association remains debated), chronic immunosuppression in organ transplant patients, and phosphodiesterase-5 inhibitors such as sildenafil.

Clinical Presentation

Acute CSC

Acute CSC presents with sudden unilateral blurred vision, metamorphopsia, micropsia, and a central scotoma. Visual acuity is often only mildly reduced, typically in the 20/20 to 20/40 range. The dome of subretinal fluid beneath the fovea acts as a minus lens, producing a relative hyperopic shift. Dyschromatopsia and decreased contrast sensitivity are common. The condition is self-limited in 80 to 90% of cases, resolving spontaneously within three to four months.

Chronic CSC

Chronic CSC is defined as persistent subretinal fluid lasting longer than three to six months or recurrent episodes. As the disease persists, RPE atrophy develops, subretinal deposits accumulate, and gravitational tracts -- tracks of fluid that descend inferiorly under the influence of gravity -- become visible. Visual acuity progressively deteriorates. Secondary choroidal neovascularization may develop, and there is a real risk of permanent photoreceptor damage and irreversible vision loss.

<image>Fundus photograph of acute central serous chorioretinopathy showing a well-circumscribed dome-shaped neurosensory detachment at the macula, with corresponding OCT demonstrating subretinal fluid, thickened choroid, and focal RPE elevation</image>

Diagnostic Imaging

OCT

OCT is the primary imaging modality for CSC. It demonstrates a dome-shaped neurosensory retinal detachment, focal pigment epithelial detachments (which may be serous or fibrovascular), and markedly increased subfoveal choroidal thickness -- typically exceeding 300 micrometers and often greater than 400 micrometers. Enhanced depth imaging reveals dilated choroidal vessels (pachyvessels) in the Haller layer. In chronic CSC, additional findings include elongated photoreceptor outer segments, subretinal deposits, ellipsoid zone disruption, and RPE irregularity.

Fluorescein Angiography (FA)

Fluorescein angiography identifies the specific site of RPE leakage. The classic "smokestack" pattern -- a focal point of hyperfluorescence with an ascending plume of dye -- is the textbook description but is actually seen in only 10 to 20% of cases. The more common inkblot pattern shows a focal point of hyperfluorescence that expands concentrically. In chronic CSC, FA reveals diffuse RPE window defects, granular hyperfluorescence, and gravitational tracts.

Indocyanine Green Angiography (ICGA)

ICGA is particularly useful for visualizing the choroidal abnormalities that underlie CSC. It demonstrates choroidal hyperpermeability as mid-phase hyperfluorescence and reveals dilated pachyvessels. ICGA provides better delineation of choroidal pathology than FA and is useful for guiding the placement of photodynamic therapy.

Fundus Autofluorescence (FAF)

In acute CSC, FAF shows hypoautofluorescence at the leak point and hyperautofluorescence in the area of subretinal fluid. In chronic disease, hypoautofluorescent areas correspond to RPE atrophy, and descending gravitational tracts are clearly visualized.

Management

Observation (Acute CSC)

Observation is the first-line approach for acute CSC, with a watchful waiting period of three to four months. Since 80 to 90% of cases resolve spontaneously, intervention is not warranted in most initial presentations. The most important step is to discontinue exogenous corticosteroids if the patient is using them by any route. Stress reduction, sleep hygiene, and screening for obstructive sleep apnea address additional modifiable risk factors.

Photodynamic Therapy (PDT) with Verteporfin

Photodynamic therapy is the most effective treatment for CSC, with the strongest evidence base of any intervention. Half-dose (3 mg/m2) or half-fluence PDT is preferred over full-dose treatment to reduce the risk of choroidal ischemia. The PLACE trial demonstrated that half-dose PDT is superior to micropulse laser for chronic CSC, achieving complete resolution of subretinal fluid in 67% of patients compared with 29% for micropulse laser at eight months. PDT works by inducing vascular remodeling and reducing choroidal hyperpermeability. Treatment can be guided by ICGA hot spots to target the areas of greatest choroidal abnormality. Risks with reduced-dose PDT are rare but include RPE atrophy, secondary CNV, and choroidal ischemia.

Mineralocorticoid Receptor Antagonists (MRAs)

Eplerenone (50 mg daily) and spironolactone (25 to 50 mg daily) have been investigated based on the rationale that mineralocorticoid receptor activation contributes to choroidal vasodilation and fluid leakage. However, the VICI trial comparing eplerenone with placebo for chronic CSC found no significant difference in best-corrected visual acuity at 12 months. While some anatomical improvement in subretinal fluid reduction was observed, it was not clinically meaningful. Results across studies have been mixed, and MRAs are not recommended as monotherapy based on current evidence. Side effects include hyperkalemia with eplerenone and gynecomastia with spironolactone. MRAs may have a limited role as adjunctive therapy in selected cases.

Focal Laser Photocoagulation

Focal laser can be applied directly to extrafoveal leak points identified on fluorescein angiography. While it speeds the resolution of subretinal fluid, it does not improve final visual acuity compared with observation alone. It cannot be used for subfoveal or juxtafoveal leaks due to the risk of central scotoma. Its role has declined with the availability of PDT.

Micropulse Laser

Subthreshold micropulse laser can be applied to areas of RPE leakage with less collateral RPE damage than conventional photocoagulation. However, it was shown to be inferior to PDT in the PLACE trial and is primarily considered when PDT is unavailable.

<image>Fluorescein angiogram of acute CSC showing the classic smokestack leak pattern with early focal hyperfluorescence and ascending plume of dye, alongside a chronic CSC case with diffuse RPE changes and gravitational tracts</image>

Complications

CSC recurs in 30 to 50% of patients within five years, often in the same eye. Chronic subretinal fluid leads to progressive photoreceptor degeneration and RPE atrophy. Secondary choroidal neovascularization may develop in the setting of chronic CSC, representing progression along the pachychoroid spectrum to pachychoroid neovasculopathy. Permanent visual impairment results from cumulative RPE and photoreceptor damage. Bilateral involvement occurs in 30 to 40% of patients, though the fellow eye may be subclinically affected.

<image>EDI-OCT comparison showing markedly increased subfoveal choroidal thickness with dilated pachyvessels in CSC versus normal choroidal thickness, and chronic CSC with RPE irregularity and subretinal deposits</image>

Clinical Pearls

Every patient presenting with unexplained subretinal fluid should be asked about corticosteroid use by all routes -- systemic, inhaled, topical, epidural, and nasal. When CSC develops in a patient taking corticosteroids, discontinuing the steroid is the single most important intervention. Periocular or intravitreal corticosteroids must never be used to treat CSC, as they will worsen the condition. Acute CSC in young patients should be observed initially, as the vast majority resolve spontaneously. For chronic CSC persisting beyond three to six months, half-dose PDT is the best-supported treatment. Mineralocorticoid receptor antagonists have been disappointing in randomized controlled trials and should be used with tempered expectations. The fellow eye should always be evaluated, as subclinical choroidal thickening or RPE changes are common. CSC must be distinguished from wet AMD: CSC patients are younger, have thicker choroids, and lack drusen. In women of childbearing age, pregnancy and oral contraceptive use should be considered as contributing factors. Long-standing chronic CSC with extensive gravitational RPE changes can be misdiagnosed as dry AMD if the clinical history is not carefully reviewed.

References

• Daruich A, et al. Central serous chorioretinopathy: recent findings and new physiopathology hypothesis. Prog Retin Eye Res. 2015;48:82-118.
• van Dijk EHC, et al. Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (PLACE trial). Ophthalmology. 2018;125(10):1547-1555.
• Lotery A, et al. Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease (VICI trial). Lancet. 2020;395(10220):294-303.
• Cheung CMG, et al. Pachychoroid disease. Eye. 2019;33(1):14-33.
• American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous.

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