Central serous chorioretinopathy (CSC) is characterized by serous retinal detachment and or retinal pigment epithelial (RPE) detachment, most often confined to the macula, with leakage of fluid through the RPE into the subretinal space. CSC is seen frequently in retina practices and is classically described in young male patients with no associated systemic conditions. CSCR has also been described as an idiopathic maculopathy characterized by a thickened choroid, RPE detachment, and variable subretinal fluid.

The modern concept of CSC is grounded in an evolving understanding of where the primary abnormality lies and how fluid reaches the subretinal compartment. The disease has been known since the original description by von Graefe in 1866. In the historical development summarized in the literature, fluorescein angiographic leakage at the level of the RPE highlighted the choroid and RPE as key tissues involved, and CSC is presented as a condition in which hyperpermeability of the choroid causes leakage through the RPE, resulting in a neurosensory retinal detachment. In parallel descriptions, CSC is defined as a serous retinal detachment with or without pigment epithelial detachment (PED), most commonly seen in the macular region.

Across reviews, CSC is repeatedly framed as a disorder that preferentially affects men and tends to occur in working age groups. In one population based study cited in a major review, the annual incidence was reported as 9.9 cases per 100,000 men and 1.7 per 100,000 women in Olmstead County, Minnesota. In another review summary, CSC is described as classically occurring in a middle-aged man and as being observed across a broad adult age range from 20 to 64 years, with reported male:female ratios ranging from 2.6:1 to 6:1. In a pathophysiology focused review, CSCR is described as affecting mainly middle-aged males with a mean age of 40 years.

Clinical presentation is variable and can include both symptomatic and initially silent disease. Some patients are initially asymptomatic. When symptomatic, CSCR is reported to present with blurred vision, metamorphopsia, dyschromatopsia, central scotoma, hypermetropization, and micropsia. Symptoms are often reported in one eye, although bilateral involvement can be detected in up to 40% of cases, and another review similarly notes bilateral disease in 14% to 40% of cases.

Natural history is commonly described as self-limiting, but persistent or recurrent disease is also emphasized. In a review of multimodal imaging and pathophysiology, CSC is described as having a self-limiting course while also being associated with presentations that are persistent, recurrent, or bilateral with distressing visual loss. In a detailed clinical review, the acute form generally resolves spontaneously with minimal sequelae. In another statement focused on the time course of recovery, visual acuity recovery is described as typically occurring within one to four months, coinciding with reattachment of the neurosensory retina, while recurrences are described as common, occurring in approximately 30% to 50% of patients by one year.

Chronic disease is presented as a distinct pathological state in which the outer retina and RPE can become structurally compromised. In one review, chronic CSC can result in widespread RPE damage, sometimes referred to as diffuse retinal pigment epitheliopathy (DRPE), and is described as involving longstanding subretinal fluid that cannot be reabsorbed efficiently because of choroidal disease and extensive dysfunction and loss of RPE. In that same description, chronic fluid is linked to photoreceptor death and the possibility of permanent visual loss, and chronic CSC is described as being more likely to be complicated by choroidal neovascularization (CNV) that can cause severe visual loss. A separate review likewise notes that some patients have persistent or recurrent disease beyond three months and describes chronic CSCR as involving multifocal or diffuse RPE disruption and atrophy throughout the posterior pole, with severe visual loss as a potential outcome. Additional structural correlates of permanent visual loss listed in this context include RPE atrophy, outer retinal atrophy, secondary CNV, cystoid macular edema (CME), and choriocapillaris atrophy.

Risk factors and systemic associations are described as heterogeneous, but several themes are consistently repeated across reviews. Numerous risk factors have been reported, and the most consistent is the use of glucocorticoids. A meta analysis synthesizing multiple studies reported significant associations with hypertension, Helicobacter pylori infection, steroid usage, sleeping disturbance, autoimmune disease, psychopharmacologic medication use, and Type A behavior. In a multimodal imaging review, CSCR is described as predominantly affecting young men and as having risk factors including corticosteroid use, the Type A behavior pattern, and psychological stress. A detailed review of risk exposures notes a very consistent association between CSC and exogenous corticosteroid use, most commonly with systemic administration, while also describing associations with other routes including intranasal, topical dermal, intra-articular, epidural, and periocular corticosteroids.

Mechanistic framing in the eligible sources converges on choroidal pathology with downstream RPE barrier failure, while also acknowledging substantial uncertainty about how individual pathways contribute. The alteration in choroidal circulation is described as probably the main mechanism leading to CSC. In the same discussion, autonomic dysfunction with increased sympathetic and decreased parasympathetic activity is proposed to impair choroidal vascular homeostasis and lead to choroidal hyperperfusion, ultimately resulting in subretinal fluid (SRF) accumulation. Type A personality is described as including competitive drive, a sense of urgency, hostile temperament, and aggressive nature, and is linked in the review to activation of the neuroendocrine system with release of catecholamines and corticosteroids, with a stated consequence of altered choroidal permeability.

A pathophysiology review explicitly emphasizes uncertainty, stating that the pathogenesis of CSCR is poorly understood. In that framing, choroid hyperpermeability and RPE dysfunction are described as cornerstones for developing CSCR, while mechanisms at retinal, vascular, RPE, and cellular levels continue to be an enigma. The same source reports that no single mechanism in the literature is supported by a large number of sufficiently sized and good quality studies. Within the mechanistic model presented, imaging advances are also used to reinforce a choroid first paradigm: choroid vascular hyperpermeability is described as a hallmark, with hyperpermeable regions localizing to a thickened subfoveal choroid, also termed pachychoroid, consistent with choroidal vessel dilation and congestion. A further hypothesis described in the same text links ischemia from choriocapillaris compression and increased choroid parenchyma hydrostatic pressure to an overwhelmed RPE barrier, with a cascade of RPE dysfunction, detachment, and micro-rips culminating in fluid accumulation in the subretinal space.

The sources also connect CSC to a broader phenotypic spectrum defined by choroidal thickening. CSCR is described as part of the pachychoroid disease spectrum and is characterized by thick choroid with serous retinal detachment at the macula and RPE detachment with subsequent atrophy. A multimodal imaging review similarly states that CSC is part of the spectrum of pachychoroid disease. In an imaging focused review, CSCR is described within the spectrum of pachychoroid diseases that share similar features of choroidal thickening and RPE changes.

Imaging is central to describing CSC pathology in vivo, and multiple modalities are explicitly listed as relevant. Multimodal imaging techniques include optical coherence tomography (OCT) with enhanced depth imaging, fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography. Enhanced depth imaging OCT is described as demonstrating a thickened and engorged choroid. FA in acute CSCR is described as revealing focal leakage, sometimes called an expansile dot, in the majority of cases, and a smokestack pattern in 10% to 20% of patients. In chronic CSCR, FA may show multiple areas of mottled hyperfluorescence, indicating widespread patchy RPE dysfunction or atrophy.

ICGA is described as detecting impaired choroidal circulation, including choroidal hypoperfusion, delays in choroidal circulation, and hyperfluorescence corresponding to areas of choroidal hyperpermeability. Fundus autofluorescence (FAF) is described as detecting endogenous fluorophores in lipofuscin of RPE cells, providing information regarding the health of the RPE. FAF patterns in acute CSCR are described as including confluent or granular hypoautofluorescence signifying loss of RPE cells and hyperautofluorescence representing accumulation of unphagocytized photoreceptor outer segments, while chronic CSCR is described as showing multifocal or diffuse mottled hypoautofluorescence representing RPE atrophy. Descending tracts, also referred to as guttering, are also described as being seen with increased and decreased autofluorescence.

OCT is described as enabling rapid noninvasive identification of PED, CME, subretinal fluid, and other structural abnormalities, and enhanced depth imaging OCT is described as detecting increased choroidal thickness that is characterized as typical of CSCR. This multimodal framework is used throughout the eligible sources to link clinical phenotypes such as acute self-limited detachment, chronic DRPE, and complications such as CNV to observable patterns of RPE alteration, choroidal hyperpermeability, and choroidal thickening.

Finally, some mechanistic sources explicitly position CNV within a proposed chain of events in chronic pathology. In a schematic description of CSCR pathophysiology, multiple potential drivers are listed, including mineralocorticoid receptor activation, vortex vein compression, and dysregulation of complement or adrenergic pathways, each stated as capable of producing choroidal vessel hyperpermeability or direct injury to RPE cells. Within the same schematic description, RPE cells are described as becoming overwhelmed and unable to provide an adequate barrier, resulting in subretinal fluid accumulation, and prolonged ischemia is proposed to stimulate the release of angiogenic factors such as VEGF, resulting in CNV. Taken together, the eligible evidence supports a pathology centered on choroidal vascular hyperpermeability and thickening with secondary RPE dysfunction, producing serous macular detachment that is often self-limited but can recur, persist, or evolve into chronic disease with structural damage and vision-threatening complications.

References

Nicholson B., Noble J., Forooghian F., Meyerle C. Central Serous Chorioretinopathy: Update on Pathophysiology and Treatment. Surv Ophthalmol (2013). PMCID: PMC3574296.

Manayath G. J. et al. Central serous chorioretinopathy: Current update on pathophysiology and multimodal imaging. Oman J Ophthalmol (2018). PMCID: PMC5991069.

Iyer P. G. et al. Central Serous Chorioretinopathy: Multimodal Imaging and Management Options. Case Rep Ophthalmol Med (2020). PMCID: PMC7443246.

Bal M. S. et al. Pathophysiology of central serous chorioretinopathy: a literature review with quality assessment. Eye (Lond) (2022). PMCID: PMC9046392.