The role of the choroidal nervous system in central serous chorioretinopathy and associated diseases

Central serous chorioretinopathy (CSCR) and associated diseases, are linked to abnormal remodeling of the choroidal vasculature, venous congestion and impaired regulation of choroidal blood flow. Although anatomical, genetic and hormonal factors have been identified, a unifying pathophysiological mechanism remains unclear. In this review, we propose that peripheral choroidal nervous system dysfunction may represent a central driver of this choroidal phenotype. First, we provide an updated overview of the organization and functions of the autonomous nervous system, its interaction with the hypothalamic-pituitary-adrenal axis, as well as the clinical tools used to assess autonomic regulation in humans. We then detail the neurovascular organization of the choroid, highlighting the dense and complex sympathetic, parasympathetic, sensory and intrinsic innervation. Experimental studies demonstrate that not only choroidal blood flow but also immune processes and other aspects of the choroidal environment, are finely regulated by choroidal innervation. Disruption of this neural control induces choroidal vascular enlargement, venous remodeling, inflammation and outer retinal damage, thereby reproducing key features of the choroidal pathology associated with CSCR. Clinical evidence further supports this framework by showing local and systemic autonomic dysregulation in patients with CSCR. This emphasizes the importance of clinical evaluations through pupillometry, heart rate variability, ambulatory blood pressure monitoring, stress biomarkers and dynamic choroidal imaging. Autonomic imbalance also provides a mechanistic link between CSCR and associated risk factors, such as psychological stress, sleep disorders, cardiovascular disease and glucocorticoid exposure.