Cushing’s Syndrome and Hypothalamic–Pituitary–Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

Recent technological advances--new pathophysiological insights, new imaging techniques for diagnosis and management, and new treatments--have led to an improved understanding of central serous chorioretinopathy (CSC). The primary role of the choroid has become more widely accepted with widespread use of indocyanine green angiography. Optical coherence tomography (OCT), and particularly enhanced depth imaging OCT, demonstrate a thickened and engorged choroid. Adaptive optics, fundus autofluorescence, multifocal electroretinography, microperimetry, and contrast sensitivity testing reveal that patients with even a mild course suffer previously undetected anatomic and functional loss. Although focal laser and photodynamic therapy are the current standard of care for persistent subretinal fluid in CSC, they are not appropriate in all cases, and the optimal timing of intervention remains unclear. Published by Elsevier Inc.

Central serous chorioretinopathy (CSC) is a disease of the retina characterized by serous detachment of the neurosensory retina secondary to one or more focal lesions of the retinal pigment epithelium (RPE). CSC occurs most frequently in mid-life and more often in men than in women. Major symptoms are blurred vision, usually in one eye only and perceived typically by the patient as a dark spot in the centre of the visual field with associated micropsia and metamorphopsia. Normal vision often recurs spontaneously within a few months. The condition can be precipitated by psychosocial stress and hypercortisolism. Ophthalmoscopic signs of CSC range from mono- or paucifocal RPE lesions with prominent elevation of the neurosensory retina by clear fluid - typical of cases of recent onset - to shallow detachments overlying large patches of irregularly depigmented RPE. The spectrum of lesions includes RPE detachments. Granular or fibrinous material may accumulate in the subretinal cavity. Serous detachment often resolves spontaneously. From first contact, counselling about the potential relation to stress and glucocorticoid medication is warranted. After 3 months without resolution of acute CSC or in chronic CSC, treatment should be considered. Resolution of detachment can usually be achieved in acute CSC by focal photocoagulation of leaking RPE lesions or, in chronic CSC, by photodynamic therapy. The effect of therapy on long-term visual outcome is insufficiently documented. Reattachment within 4 months of onset is considered a relevant therapeutic target because prolonged detachment is associated with photoreceptor atrophy. This suggests that the value of treatment depends upon proper selection of cases that will not resolve without therapy. Chronic CSC may be difficult to differentiate from occult choroidal neovascularization secondary to CSC. Patients with chronic CSC who receive glucocorticoid treatment for systemic disease can often be managed without having to discontinue this medication.