Basak Selin Kara

Introduction

Central serous chorioretinopathy (CSCR) is a chorioretinal disorder defined by serous detachment of the neurosensory retina. The disease commonly involves the macula (1,2). The disease most commonly affects young to middle-aged adults (2). It represents a major cause of central visual complaints in people between the ages of 35-55. (2). CSCR is usually a self-limiting condition. However, chronic or recurrent disease can cause persistent visual symptoms and irreversible changes to the retinal pigment epithelium (RPE) and outer retina (3). New developments in retinal imaging have significantly evolved understanding of CSCR pathophysiology. It is currently recognised primarily as a disorder of choroidal vascular dysfunction within the pachychoroid disease spectrum, instead of a condition stemming from RPE abnormalities (4,5).

Aetiology and Pathophysiology

Initial descriptions of CSCR focused on focal defects in the RPE that permitted leakage of fluid into the subretinal space (1). While RPE dysfunction remains an important component of disease mechanism, new evidence revealed choriocentric mechanism as the primary driver of CSCR. Indocyanine green angiography (ICGA) shows areas of choroidal hyperpermeability and venous engorgement extending beyond regions of neurosensory retinal detachment, which suggests a diffuse choroidal abnormality rather than a focal RPE defect (4). Enhanced depth imaging optical coherence tomography (EDI-OCT) findings further support this by consistently demonstrating increased subfoveal choroidal thickness in affected and asymptomatic fellow eyes of patients with active CSCR (5). These findings place CSCR within the pachychoroid disease spectrum.

Corticosteroid exposure is one of the most well known risk factors for CSCR. Both systemic, inhaled, intranasal, topical, and intra-articular corticosteroid use, as well as endogenous hypercortisolism are found to be associated with CSCR development (6). Activation of mineralocorticoid receptors within the choroid has been shown to result in vasodilation, increased vascular permeability, and choroidal thickening which are mechanisms involving in disease development (7).

Psychosocial stress has long been implicated as a precipitating factor for CSCR, “Type A” personality traits and heightened stress reactivity are specifically found to be linked to disease progression (2). Moreover a meta-analysis identified male sex, corticosteroid use, psychosocial stress, and systemic vascular risk factors as significant contributors to CSCR development (8).

More recent models propose that CSCR arises from a combination of choroidal vascular hyperpermeability, hormonal influences, autonomic dysregulation, and secondary RPE decompensation (9). This framework helps explain the heterogeneous clinical presentation of CSCR and the variability in disease course and treatment response.

Clinical Presentation

CSCR typically presents in young to middle-aged adults, with a marked male predominance (2,8). Most common symptoms reported by patients are acute or subacute onset of central visual disturbance, which may be unilateral or bilateral. Other symptoms include blurred central vision, metamorphopsia, micropsia, reduced contrast sensitivity, and a central scotoma (2). Visual acuity may be only mildly reduced despite significant subjective visual impairment which shows preferential involvement of the outer retina and photoreceptor alignment rather than generalised retinal thickening (3).

Symptoms are often fluctuating. Some patients describe worsening vision in the morning. This is likely to be a reflection of diurnal variation in choroidal thickness and cortisol levels (2). Many cases resolve spontaneously within weeks to months; however, others follow a recurrent or persistent course. Chronic CSCR is commonly defined by persistence of subretinal fluid for more than three to four months. It is associated with progressive RPE damage, photoreceptor disruption, and reduced retinal sensitivity, resulting long-term visual dysfunction even after anatomical resolution of disease (3).

Imaging Findings

Optical coherence tomography (OCT) is the principal diagnostic modality used in CSCR. In acute disease, OCT demonstrates serous detachment of the neurosensory retina with optically clear subretinal fluid and relative preservation of the outer retinal layers (5). Small pigment epithelial detachments may be present at sites of leakage. OCT can reveal thinning or disruption of the ellipsoid zone, RPE irregularities, and subretinal hyperreflective material in chronic disease which reflects cumulative retinal injury (3).

Enhanced depth imaging OCT (EDI-OCT) provides valuable information on choroidal involvement. EDI OCT images consistently demonstrates increased subfoveal choroidal thickness in eyes with active CSCR (5). This finding reinforces classification of CSCR within the pachychoroid disease spectrum.

Fluorescein angiography (FA) classically demonstrates focal leakage at the level of the RPE. The most common leakage pattern is the “ink-blot” configuration while a “smoke-stack” pattern can be also less frequently be observed (1). While FA is useful for identification leakage sites and excluding alternative diagnoses, it offers limited information regarding underlying choroidal pathology.

Indocyanine green angiography (ICGA) has been demonstrated to be useful in CSCR, since it reveals choroidal hyperpermeability, venular dilation, and delayed choroidal filling (4). These observations have directly influenced therapeutic strategies, including the use of photodynamic therapy targeting choroidal abnormalities rather than focal RPE leaks alone.

Management

Management of CSCR is decided considering the disease duration, severity, and functional impact. In acute, first-episode CSCR, observation with reassurance can be appropriate since most of the cases resolve spontaneously within three months. Identification and modification of risk factors, cessation or reduction of corticosteroid exposure are also important in long term disease management and prevention (6).

In recurrent or chronic CSCR, intervention may be required to reduce choroidal hyperpermeability and enhance resolution of subretinal fluid. Verteporfin photodynamic therapy with reduced-dose or reduced-fluence protocols has been demonstrated to provide the most consistent anatomical and functional benefit by inducing choroidal vascular remodelling and reducing vascular permeability (10). Pharmacological approaches that intervene in mineralocorticoid pathways have been investigated. Although early studies suggested benefit of pharmacological treatments, randomised controlled trials failed to prove a clear superiority of the medications over placebo which limit their routine clinical use (11). Anti-vascular endothelial growth factor therapy is generally reserved for complicated cases with secondary choroidal neovascularisation. Sub-threshold macula laser is an emerging treatment modality for CSCR (12).

Conclusion

In short, central serous chorioretinopathy is a complex chorioretinal disorder caused by choroidal vascular dysfunction. It has associations with corticosteroid exposure, psychosocial stress, and hormonal factors. The disease prognosis is often favourable. However, recurrent and chronic CSCR possesses the risk of irreversible retinal damage and persistent visual dysfunction. While managing a patient with CSCR, comprehensive understanding of disease mechanisms is necessary.

References

1. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. Am J Ophthalmol. 1967;63(3 Suppl):1–139.
2. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc. 1986;84:799–845.
3. Baran NV, Gürlü VP, Esgin H. Long-term macular function in eyes with central serous chorioretinopathy. Clin Exp Ophthalmol. 2005;33(4):369–72.
4. Prünte C, Flammer J. Choroidal capillary and venous congestion in central serous chorioretinopathy. Am J Ophthalmol. 1996;121(1):26–34.
5. Jirarattanasopa P, Ooto S, Tsujikawa A, et al. Assessment of macular choroidal thickness by optical coherence tomography and angiographic changes in central serous chorioretinopathy. Ophthalmology. 2012;119(8):1666–78.
6. Carvalho-Recchia CA, Yannuzzi LA, Negrão S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology. 2002;109(10):1834–7.
7. Zhao M, Célérier I, Bousquet E, et al. Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. J Clin Invest. 2012;122(7):2672–9.
8. Liu B, Deng T, Zhang J. Risk factors for central serous chorioretinopathy: a systematic review and meta-analysis. Retina. 2016;36(1):9–19.
9. Daruich A, Matet A, Dirani A, et al. Central serous chorioretinopathy: recent findings and new physiopathology hypothesis. Prog Retin Eye Res. 2015;48:82–118.
10. Taban M, Boyer DS, Thomas EL, Taban M. Chronic central serous chorioretinopathy: photodynamic therapy. Am J Ophthalmol. 2004;137(6):1073–80.
11. Lotery A, Sivaprasad S, O’Connell A, et al. Eplerenone for chronic central serous chorioretinopathy (VICI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10220):294–303.
12. Schworm B, Siedlecki J, Keidel LF, Herold TR, Luft N, Priglinger SG. Subthreshold laser therapy with a standardized macular treatment pattern in chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2021 Nov;259(11):3271-3281. doi: 10.1007/s00417-021-05256-3. Epub 2021 Jun 10. PMID: 34110452; PMCID: PMC8523443.