Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease that causes serous retinal detachment (SRF) in the macula, and fluorescein angiography (FA) shows leakage at the RPE level.
It predominantly affects men in their 30s to 40s, with a male-to-female ratio of approximately 8:1.
Steroids are the greatest risk factor (OR 37.1), and all routes of administration carry a risk of onset.
Most typical cases resolve spontaneously within 3–4 months, but if SRF persists for more than 6 months, active treatment is required as a chronic type.
The first-line treatment for chronic type is half-dose PDT (photodynamic therapy). The PLACE trial showed significant superiority over micropulse laser, and the SPECTRA trial showed a complete SRF resolution rate of 78% at 12 weeks vs. 17% for eplerenone⁹⁾.
It is part of the pachychoroid disease spectrum, and the pachychoroid group has a lower rate of spontaneous resolution than the non-pachychoroid group (28.8% vs. 48%)³⁾.
The combination of FA and OCT is fundamental for diagnosis, and IA is useful for evaluating choroidal abnormalities and differential diagnosis.

1. What is Central Serous Chorioretinopathy?

Central Serous Chorioretinopathy (CSC) is a disease in which serous retinal detachment (SRF) occurs in the macula. Fluorescein angiography (FA) shows leakage at the level of the retinal pigment epithelium (RPE). It is considered the fourth most common retinal disease after age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. It was first described by von Graefe in 1866 as “central recurrent retinitis,” and the current name was given by Gass et al. in 1967. In Japan, it was previously often used to refer only to typical cases (so-called central retinitis) with localized retinal detachment in the macula, but it is now classified into three subtypes. Many cases heal spontaneously, but in cases where SRF persists, visual prognosis may worsen.

Epidemiologically, the incidence is 9.9 per 100,000 men and 1.7 per 100,000 women, with a male-to-female ratio of about 8:1⁴⁾. In a study of 250 eyes, the mean age was 46.6 years, and 88.4% were male³⁾.

This disease has the following three subtypes.

Typical Type

Patient population: Predominantly men in their 30s–40s. Usually unilateral.

Pathology: Localized serous retinal detachment in the macula.

Course: Most cases resolve spontaneously within 3–4 months. Visual prognosis is generally good.

Chronic Type

Patient population: More common in older adults. Often bilateral. Recently increasing.

Pathophysiology: Extensive RPE damage. Often recurs.

Course: SRF persists for 6 months or longer. Requires active treatment ⁵⁾.

Bullous retinal detachment

Patient population: Common in cases with high-dose steroid use. Corresponds to what was previously called multiple posterior pole retinal pigment epitheliopathy in Japan.

Pathophysiology: Severe form with bullous retinal detachment. Accompanied by large RPE detachment (PED) and multiple white spots.

Course: The extent of SRF often reaches the lower fundus, and visual prognosis may be poor.

The recurrence rate is high, up to 50% within one year. This condition is considered part of the pachychoroid disease spectrum (a group of diseases characterized by choroidal thickening) ³⁾⁹⁾.

Q Does it heal on its own?

In typical cases, spontaneous remission often occurs within 3 to 4 months, and visual prognosis is generally good. However, the recurrence rate reaches up to 50% within one year. If SRF persists for 6 months or longer, it is considered chronic and requires treatment such as PDT. In the pachychoroid group, the spontaneous resolution rate is lower (28.8%) than in the non-pachychoroid group (48%), and the recurrence rate is higher (31.2% vs. 10.4%), so caution is needed ³⁾.

2. Main symptoms and clinical findings

OCT of central serous chorioretinopathy. Serous retinal detachment and mild PED are seen in the macula.

Koizumi H, et al. Central serous chorioretinopathy and the sclera: what we have learned so far. Jpn J Ophthalmol. 2024. Figure 4. PMCID: PMC11420308. License: CC BY.

Macular OCT shows shallow serous retinal detachment with subretinal fluid under the fovea. Findings suggestive of small RPE elevation and choroidal thickening are also present, indicating the clinical picture of central serous chorioretinopathy.

Subjective symptoms

Decreased vision: Often relatively mild. Hyperopic shift correctable with a mild convex lens is the most common complaint.
Metamorphopsia: Objects appear distorted. Along with central scotoma, it is an uncomfortable symptom for patients and can interfere with driving and work.
Micropsia: Objects appear smaller than they actually are.
Central scotoma: The central part of the visual field becomes dark.
Decreased contrast sensitivity: May be accompanied by color vision abnormalities (acquired blue-yellow color vision deficiency).

When subretinal fluid is absorbed, central scotoma and metamorphopsia improve relatively early. On the other hand, micropsia and decreased contrast sensitivity may persist. In the chronic type, recurrences are frequent, and many cases have poor visual acuity. Typical cases are often unilateral, while chronic type and bullous retinal detachment are often bilateral.

Clinical Findings

The following findings are observed with slit-lamp microscopy and various imaging tests.

Serous retinal detachment (SRF): A round or oval elevation without macular hemorrhage.
Retinal pigment epithelial detachment (PED): Observed in up to 63% of cases on OCT.
Precipitates: White dot-like deposits on the posterior surface of the detached retina. They are found in areas prone to pigment epithelial detachment and serous retinal detachment.
Subretinal fibrin deposition (white plaques): May be observed corresponding to areas of fluorescein leakage.
Choroidal thickening: Evaluated by EDI-OCT (Enhanced Depth Imaging OCT). While normal thickness is 250–300 μm, in this condition it becomes 350–450 μm or more. The subfoveal choroidal thickness (SFCT) in the pachychoroid group has been reported as 406.6 ± 80.8 μm ³⁾. In some cases, it can reach up to 500 μm.
Dilation of Haller’s layer vessels and thinning of Sattler’s layer: Characteristic changes in choroidal structure that can be confirmed by EDI-OCT ³⁾.

In the chronic type, pigment epithelial damage is extensive, and retinal detachment extending downward with atrophic bands of the pigment epithelium may be observed. In bullous retinal detachment, the retinal detachment is severe and often extends to the lower fundus, accompanied by large pigment epithelial detachments and multiple white plaques.

3. Causes and Risk Factors

The underlying cause of this condition remains unknown, but increased permeability of choroidal vessels is considered the essence. Stress and steroids are known to be related to the onset and exacerbation of this condition. The following risk factors have been reported.

Risk factor	Strength of association	Notes
Steroids	OR 37.1¹⁾	All routes of administration
Type A personality	Moderate	Stress-related
Pregnancy	0.008%/year⁷⁾	Frequent spontaneous remission after delivery
OSA	61% of patients⁹⁾	Sympathetic hyperactivity
PDE5 inhibitors	Case report⁸⁾	Resolved after discontinuation

Steroids: The greatest risk factor. Any route of administration (systemic, topical, inhaled, epidural, eye drops) carries a risk of onset. Cases have been reported after steroid administration in patients with systemic lupus erythematosus (SLE), with an OR of 37.1 (95% CI 6.2–221.8), which is extremely high¹⁾. Since steroids are associated with the onset and exacerbation of this condition, it is important to consider discontinuation or dose reduction in patients currently using them. Management should be tailored to each case in collaboration with other departments.
Psychiatric medications: Cases have been reported after taking quetiapine (an atypical antipsychotic). Best corrected visual acuity improved within 2 weeks of discontinuation, and complete resolution was achieved within 2 months²⁾.
PDE5 inhibitors: A case has been reported where symptoms developed after taking tadalafil 5 mg and resolved 3 months after discontinuation⁸⁾.
Pregnancy: The incidence during pregnancy is reported as 0.008% per year⁷⁾.
OSA (obstructive sleep apnea): 61% of patients are found to have OSA⁹⁾.
COVID-19 vaccine: Recurrence cases after vaccination have been reported, and activation of the HPA axis is thought to be involved⁶⁾.
H. pylori infection: 53–69% of patients have H. pylori infection, with an OR of 4.6.

Onset is explained by the multi-hit theory⁹⁾. It is thought to occur in three stages: (1) anatomical predisposition (short axial length, scleral thickening, asymmetry of vortex vein drainage, etc.), (2) triggering events (steroids, stress, OSA, etc.), and (3) decompensation.

Q What is the relationship between steroids and central serous chorioretinopathy?

Steroids are the greatest risk factor for this disease, and the risk increases with all routes of administration, including eye drops, inhalation, injection, and oral intake. The odds ratio has been reported to be extremely high at 37.1¹⁾. If diagnosed with this disease and currently using steroids, consult with your doctor and consider reducing or discontinuing them as much as possible. If steroids are being administered for a systemic disease, it is necessary to coordinate with other departments on a case-by-case basis.

4. Diagnosis and Examination Methods

The diagnosis of this disease is based on a combination of FA and OCT. The main features of the examinations are shown below.

Examination	Characteristic Findings	Main Role
FA	Punctate fluorescein leakage	Identification of leakage point and treatment planning
IA (ICG)	Choroidal hyperfluorescence	Evaluation of choroidal abnormalities and differential diagnosis
OCT	Visualization of SRF and pigment epithelial detachment	Follow-up and quantification

Details of each examination are as follows.

Fluorescein angiography (FA): This is an essential test for diagnosis and treatment planning of this disease. The basic finding is punctate fluorescein leakage from the RPE, appearing as punctate hyperfluorescence in the early phase, which expands over time and accumulates under the retina. There are two types of leakage morphology: inkblot type and smokestack type. Typical leakage patterns are inkblot (31%) and smokestack (12%). Leakage points are often single in typical cases, but multiple points are often seen in bullous retinal detachment. In chronic cases, granular hyperfluorescence and late diffuse weak leakage are observed, and individual leakage points are often difficult to identify.
Indocyanine green angiography (IA/ICG): In the mid-phase, choroidal hyperfluorescence (abnormal choroidal tissue staining) is observed. This finding is seen in all disease types, but is more extensive and intense in chronic and bullous retinal detachment compared to typical cases, and is seen bilaterally. It is useful for evaluating pachychoroid changes and differential diagnosis (CNV/PCV).
OCT: It can non-invasively visualize and quantify SRF and pigment epithelial detachment. It is particularly powerful for detecting shallow retinal detachment. Elongation of photoreceptor outer segments (icicle-like changes) is also observed. EDI-OCT (spectral-domain OCT choroidal observation mode) allows accurate assessment of choroidal thickness. While normal subfoveal choroidal thickness is 250–300 μm, in this disease it is 350–450 μm (over 500 μm in some cases), demonstrating morphological choroidal abnormalities.
OCTA (OCT angiography): It can visualize flow impairment (shadow effect) in the choriocapillaris ⁶⁾.
Fundus autofluorescence (FAF): Shows hyperfluorescence in the acute phase and extensive hypofluorescence in the chronic phase. It is useful for assessing the extent of RPE damage. In chronic CSC, band-shaped hypofluorescence bordered by hyperfluorescence (atrophic tract) may be observed, which helps estimate disease duration and confirm downward migration of subretinal fluid.

Differential Diagnosis

Exudative age-related macular degeneration (especially polypoidal choroidal vasculopathy; PCV): Confirm polypoidal lesions on ICG angiography. This is an especially important differential diagnosis in patients aged 50 years or older.
Idiopathic choroidal neovascularization: Differential diagnosis is necessary when it occurs in young individuals. IA is useful for differentiation.
Vogt-Koyanagi-Harada disease (VKH): Bilateral panuveitis symptoms and multiple serous retinal detachments.
Optic pit maculopathy: SRF associated with an optic disc pit.
Lupus chorioretinopathy: Female patients, active SLE, and bilateral SRF require differentiation from this disease ¹⁾.
Retinal vascular diseases: Differentiation from diseases that cause retinal detachment in the macula, such as retinal vein occlusion and diabetic maculopathy.
Choroidal tumors: Differential diagnosis is required when accompanied by SRF.
Hypertension and preeclampsia: Can cause secondary macular SRF.
Rhegmatogenous retinal detachment: Differential diagnosis is particularly necessary in cases of bullous retinal detachment.

5. Standard Treatment

There is no established drug therapy for this condition. Laser photocoagulation of fluorescein leakage points on FA is currently the only generally accepted treatment, and the treatment strategy is determined by the type, stage, and location of leakage points.

Observation

Typical acute cases have a tendency for spontaneous remission. In the acute phase of a first episode, natural absorption of subretinal fluid is awaited for 4 to 6 months. In typical cases, complete absorption often occurs within 3 to 4 months, and visual prognosis is good. The spontaneous resolution rate is 48% in the non-pachychoroid group, compared to 28.8% in the pachychoroid group³⁾.

If symptoms are severe and the patient desires early improvement, photocoagulation may be indicated even in acute typical cases. If the patient is using steroids, reduce or discontinue as much as possible. If steroids are administered for systemic disease, manage in collaboration with other departments on a case-by-case basis.

In cases where detachment persists for more than 4 to 6 months after onset, recurrent cases, severe cases, or cases where the other eye has residual visual impairment due to this disease (chronic type, bullous retinal detachment), early absorption of subretinal fluid through treatment is necessary. This is because macular damage leads to poor visual prognosis.

Laser Photocoagulation

Indicated when the leakage point is at least 500 μm from the fovea and outside the foveal avascular zone. Directly coagulate the leakage point identified on FA (200 μm spot size, 0.2 seconds, 70–120 mW). The coagulation intensity should be mild, producing a faint gray-white coagulation spot in the deep retina. Even leakage between the optic disc and macula is not problematic with mild coagulation. If leakage is within a pigment epithelial detachment, only the leakage point needs to be coagulated.

When photocoagulation is effective, retinal detachment resolves within a few weeks. However, improvement in subjective symptoms often takes longer. Complications include accidental foveal irradiation and postoperative choroidal neovascularization (CNV) (more likely with long wavelength, short duration, small spot coagulation).

Micropulse Laser Treatment (MPLT)

A 577 nm yellow laser is used. Irradiation is performed with settings of 240 mW, 200 μm spot size, 200 ms, and 5% duty cycle⁴⁾. Since energy is selectively delivered to the RPE, no scar is formed. It can be applied directly under the fovea.

Bodea F et al. (2024) reported that in patients with central serous chorioretinopathy treated with MPLT, SRF decreased at 2 weeks and resolved at 6 weeks after treatment⁴⁾.

For this condition during pregnancy, micropulse laser is considered the only safe treatment option⁷⁾.

Observation

Indications: First-line treatment for acute typical cases.

Duration: 4–6 months. Wait for spontaneous absorption.

Note: During steroid use, consider tapering or discontinuing in coordination with other departments.

PDT (Photodynamic Therapy)

Indications: First-line treatment for chronic central serous chorioretinopathy.

Method: Half-dose (half-fluence) PDT is recommended.

Evidence: Efficacy has been demonstrated in the PLACE and SPECTRA trials (12-week SRF resolution rate 78% vs. eplerenone 17%)⁹⁾.

Micropulse Laser

Features: No scarring, can be applied directly under the fovea.

Advantage: The only treatment that can be used during pregnancy⁷⁾.

Effect: SRF reduction at 2 weeks, resolution at 6 weeks⁴⁾.

Photodynamic Therapy (PDT)

Used in cases where laser photocoagulation is not possible, such as when the leakage point is in the foveal avascular zone or in chronic types. Half-dose PDT (half the usual dose) or half-fluence PDT (half laser output) using verteporfin (Visudyne) is recommended as first-line treatment for chronic central serous chorioretinopathy⁹⁾.

The results of major clinical trials are as follows⁹⁾.

PLACE trial: Half-dose PDT was significantly superior to micropulse laser (HSML) in all indicators: SRF resolution rate, BCVA improvement, retinal sensitivity, and RPE detachment height.
SPECTRA trial: Half-dose PDT showed a significantly higher rate of complete SRF resolution compared to eplerenone (78% vs 17% at 12 weeks). At 12 months, BCVA in the initial PDT group was better than in the eplerenone → delayed PDT group.
REPLACE trial: Improvement was seen after crossover to half-dose PDT in patients who did not respond to HSML. One year after crossover, the complete SRF resolution rate was 78% (32 eyes) in the PDT group and 67% (10 eyes) in the HSML group. Retinal sensitivity improved only in the PDT group.
SPECS trial: Improvement was seen after crossover to half-dose PDT in patients who did not respond to eplerenone. Three months after crossover, the complete SRF resolution rate was 87.5% (37 eyes) in the PDT group and 22.2% (9 eyes) in the HSML group.
Importance of PDT timing: The longer the symptom duration, the lower the likelihood of ≥2-line visual improvement. It is reported that each 1-week delay reduces the chance by 4%, making timely intervention important⁹⁾. In an analysis of 57 eyes treated with half-dose PDT, no cases of foveal atrophy were observed⁹⁾.

Eplerenone

Mineralocorticoid receptor antagonist. Used at 50 mg/day. In the VICI trial (multicenter randomized double-blind placebo-controlled trial), eplerenone did not show a significant difference in BCVA improvement compared to placebo after 12 months of treatment⁹⁾. It is considered less effective than PDT, and there are case reports of no response even after 10 months of treatment⁵⁾.

Photobiomodulation (PBM)

A new treatment involving 6-minute irradiation with 590 nm yellow LED and 625 nm red LED⁵⁾. A case has been reported where, in chronic central serous chorioretinopathy with serous pigment epithelial detachment unresponsive to eplerenone, best-corrected visual acuity improved from 20/80 to 20/25 and central retinal thickness decreased from 752 μm to 296 μm (at 1 month)⁵⁾.

Q What should I do if I develop central serous chorioretinopathy during pregnancy?

The incidence of this disease during pregnancy is reported to be 0.008% per year ⁷⁾. Most cases resolve spontaneously within 3 months after delivery. If treatment is necessary, micropulse laser therapy (MPLT) is considered the only safe option during pregnancy, and it can be applied directly under the fovea without scarring ⁷⁾.

Q Which treatment is chosen?

For typical acute cases, observation for 4 to 6 months is the standard. For chronic cases with SRF persisting for more than 6 months, half-dose PDT is the first-line treatment ⁹⁾. The SPECTRA trial showed a significant difference in complete SRF resolution at 12 weeks: 78% in the PDT group versus 17% in the eplerenone group. If the leakage point is outside the foveal avascular zone, laser photocoagulation (mild coagulation) is used; for points directly under the fovea or during pregnancy, micropulse laser is chosen. Eplerenone did not show a significant difference in BCVA improvement compared to placebo in the VICI trial ⁹⁾.

6. Pathophysiology and Detailed Mechanisms

The pathogenesis of this disease is explained by a complex mechanism centered on increased permeability of choroidal vessels. Based on IA studies, it is now thought that the primary lesion is in the choroid, with secondary RPE damage. Why the choroid is affected remains largely unknown. Stress and steroids are known to be associated with the onset and exacerbation of this disease.

Basic Mechanisms

Increased permeability of choroidal vessels (mainly dilated vessels in Haller’s layer)
Increased choroidal interstitial pressure and choroidal thickening
Breakdown of the outer blood-retinal barrier at the RPE
Decreased pump function of the RPE
Accumulation of SRF in the subretinal space

On FA, this is shown as leakage of fluorescein from the pigment epithelium and pooling of dye in the subretinal space. OCT studies have shown that the choroid is thickened in this disease compared to normal eyes, providing morphological evidence of choroidal abnormality.

Multi-hit Theory (Cheung et al.)

Cheung CMG et al. (2025) explain the pathogenesis of this disease using a multi-hit theory ⁹⁾.

Anatomical predisposition: short axial length, scleral thickening, asymmetry of vortex vein drainage distribution, etc. This disease is rare in myopic eyes, and ocular morphology is involved in the pathology.
Triggering events: steroids, stress, OSA, drug administration, etc. Cases without a clear trigger are not uncommon.
Activation of compensatory mechanisms: vasodilation of Haller’s layer, formation of vortex vein anastomoses (found in approximately 90% of the pachychoroid disease spectrum ¹⁰⁾).
Decompensation: ischemia of the choriocapillaris → RPE damage → outer retinal atrophy → vicious cycle ⁹⁾.

Scleral involvement

CSC eyes have significantly thicker anterior and posterior sclera compared to normal eyes ⁹⁾. Since the vortex veins penetrate the sclera obliquely (intrascleral course of about 4 mm), scleral thickening may increase venous outflow resistance and cause choroidal congestion ⁹⁾. In 62% of CSC eyes, loculation of fluid in the suprachoroidal space is observed, and 19% show ciliochoroidal effusion ⁹⁾. In steroid-induced CSC, the sclera is thinner than in idiopathic CSC, suggesting a different role of the sclera in the pathology ⁹⁾.

Drug-induced choroidal vasodilation

PDE5 inhibitors (e.g., tadalafil): dilate and thicken choroidal vessels via increased cGMP/NO, inducing this disease ⁸⁾.
Quetiapine: a vasodilatory mechanism via D1 receptors is presumed ²⁾.

7. Latest research and future perspectives (research-stage reports)

CSC International Group Classification

A new classification based on multimodal imaging has been proposed ⁹⁾.

Simple: total area of RPE abnormalities ≤ 2 DA (disc areas)
Complex: Total area of RPE abnormalities >2 DA or multifocal
Atypical: Bullous type, RPE tear, or association with other retinal diseases

Within each category, there are subcategories of primary (first episode), recurrent, and resolved. Complex CSC has a higher risk of developing choroidal neovascularization (MNV) compared to Simple CSC. The agreement among 10 retinal specialists was κ=0.57 (moderate), and classification continues to be refined ⁹⁾.

Pachydrusen

Pachydrusen are observed in over 40% of CSC patients ⁹⁾. CSC eyes with pachydrusen have more extensive RPE abnormalities, and their morphology and distribution differ from conventional soft drusen. An association between Haller layer thickening and choriocapillaris thinning has been shown ⁹⁾.

Photobiomodulation (PBM)

PBM is attracting attention as a new treatment that does not use verteporfin. It involves irradiation with a combination of 590 nm yellow LED and 625 nm red LED ⁵⁾. It is expected as an alternative treatment in situations where verteporfin supply is a concern.

Prognostic Prediction Using the Pachychoroid Concept

The presence or absence of pachychoroid findings is becoming increasingly important as a prognostic factor for this disease. Compared to the non-pachychoroid group, the pachychoroid group has a higher recurrence rate (31.2% vs 10.4%) and a lower spontaneous resolution rate (28.8% vs 48%) ³⁾. The presence or absence of pachychoroid findings is an important indicator in determining treatment strategy.

Vaccine-Associated Central Serous Chorioretinopathy

Reports of onset and recurrence of this disease after COVID-19 vaccination have been accumulating ⁶⁾. It has been suggested that vaccine-induced activation of the HPA axis and steroid hormone-like effects may be involved.

8. References

Rao Q, Wang R, Liu C, et al. Systemic lupus erythematosus combined with central serous chorioretinopathy treated with glucocorticoids. J Int Med Res. 2023;51(3):03000605231163716.
Durmaz Engin C, Güngör SG, Yıldız Şeker DY. Central serous chorioretinopathy following oral quetiapine. GMS Ophthalmol Cases. 2023;13:Doc13.
Bhattacharyya S, Ghorpade A, Mandal S, et al. Presentation and outcome of central serous chorioretinopathy with and without pachychoroid. Eye (Lond). 2024;38:127-131.
Bodea F, Munteanu M, Balica NC, et al. Micropulse Laser Therapy in Central Serous Chorioretinopathy. Clin Pract. 2024;14:2484-2490.
Iovino C, Coppola M, Gioia AD, et al. Photobiomodulation therapy for serous pigment epithelial detachment in chronic central serous chorioretinopathy. Retinal Cases Brief Rep. 2025;19:766-770.
Sanjay S, Leo SW, Au Eong KG. Recurrent central serous chorioretinopathy following COVID-19 vaccination. Am J Ophthalmol Case Rep. 2022;27:101644.
Ochinciuc R, Roșca C, Zaharia IM, et al. Central serous chorioretinopathy in pregnancy. Rom J Ophthalmol. 2022;66(4):382-385.
Alsarhani A, Alsulaiman R, Aljehani M, et al. Central serous chorioretinopathy associated with Tadalafil. Case Rep Ophthalmol. 2022;13:1008-1011.
Cheung CMG, Lai TYY, Gomi F, et al. Pathogenesis and management of pachychoroid disease spectrum. Eye (Lond). 2025;39:819-834.
Ochinciuc U, Pop RM, Mălāescu GD, et al. Vortex vein anastomosis in pachychoroid spectrum disease. Clin Ophthalmol. 2023;17:53-62.

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