Central serous chorioretinopathy: a pathogenetic model

Abstract

Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR) remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE). Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary–hypothalamic axis response (HPA) and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1), and plasmin-α2- plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT) and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75–100 mg), because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use. The formulation of a causative model of CSCR enables us to understand how the therapeutic approach cannot be based on a generalized therapy but should be individualized for each patient, and that sometimes a combined strategy of treatment is required. Moreover a complete knowledge of the disease will help to identify patients prone to the most persistent forms of CSCR, and thus help to find a treatment.

Increased risk of coronary heart disease in male patients with central serous chorioretinopathy: results of a population-based cohort study

“…Systemic aspirin is a commonly used medication to prevent ischaemic heart attack. However, choroidal circulation abnormality is now considered one of the most possible contributing factors in CSCR 1 18 19. Delayed choroidal arterial filling and venous congestion in indocyanine green angiography1 and subretinal fibrin deposition in several patients with variant CSCR20 suggest that coagulation abnormality might have an important pathogenic role in CSCR.…”

Central Serous Chorioretinopathy: Update on Pathophysiology and Treatment

“…Elevated serum levels of plasminogen activator inhibitor-1, an inhibitor of physiologic fibrinolysis, in CSC have led to suggestions of a thrombotic mechanism for these vascular changes. 26,28,79,233 …”

Macular ganglion cell complex thickness in acute and chronic central serous chorioretinopathy

“…Several hypotheses have been suggested regarding the pathogenesis of CSCR, but none have been definitively proven. The most eligible mechanisms are focal lesions in retinal pigment epithelium (RPE) and disturbances of choroidal circulation resulting in serous detachment of the neurosensory retina [2]. Although patients affected by CSCR often have higher levels of glucocorticoids and the actions of glucocorticoids such as suppression of the collagen synthesis and the inhibition of fibroblastic activity may be the probable mechanism [3], clarifying the pathogenesis of CSCR alone is not sufficient.…”