Pathophysiology of central serous chorioretinopathy: a literature review with quality assessment

Abstract

The pathogenesis of central serous chorioretinopathy (CSCR), a pachychoroid disease, is poorly understood. While choroid hyperpermeability and retinal pigment epithelium dysfunction are cornerstones for developing CSCR, the mechanisms at the retinal, vascular, retinal pigment epithelium, and cellular level continue to be an enigma. A few preclinical studies and the development of small-sized, poorly controlled clinical trials have resulted in limited insight into the disease mechanism. Effective treatments for CSCR are still lacking as current trials have produced inconsistent results for functional and structural gains. Thus, critically evaluating the literature to explore disease mechanisms and provide an up-to-date understanding of pathophysiology can provide valuable information and avenues to new treatments. In this study, a comprehensive summary of the mechanistic insight into CSCR is presented while highlighting the shortcomings of current literature. The mechanism was divided into seven sub-categories including mechanical obstruction, inflammation, oxidative stress, paracrine factors, autonomic dysfunction, mineralocorticoid receptors activation, and medications. We implemented validated tools like the JBI and CAMARADES to objectively analyze the quality of both clinical and preclinical studies, respectively. Overall, our analysis of the literature showed that no single mechanism was populated with a large number of sufficiently sized and good-quality studies. However, compiling these studies gave hints not only to CSCR pathogenesis but also pachychoroid disease in general while providing suggestions for future exploration.

Fig. 1. CSCR phenotype.

A Two different optical coherence tomography images showing subretinal fluid and pigment epithelial detachment. B The left panel shows a fundus photograph of a patient with chronic CSCR. The right panel is the corresponding red-free FAF image showing gravitational track region (yellow arrow) with RPE atrophy.

Fig. 2. CSCR pathophysiology.

The schematic shows the potential mechanisms for developing CSCR. Various factors including mineralocorticoid receptor activation, vortex vein compression (venous congestion), dysregulation of complement or adrenergic pathway can result in choroidal vessel hyperpermeability or direct injury to RPE cells. Elevated hydrostatic may cause compression of choriocapillaris leading to ischemic damage to RPE cells, pigmented epithelial detachment, micro-rips or atrophy. RPE cells are overwhelmed and unable to provide adequate barrier resulting in subretinal fluid accumulation. Accumulation of subretinal fluid may be further exacerbated by changing Müller cell’s water and ion homeostasis via corticosteroids. Prolonged ischemia can stimulate the release of angiogenic factors like VEGF resulting in CNV. CNV choroidal neovascularization, HTN Hypertension, LCN2 lipocalin 2, OSA obstructive sleep apnea, PAI-1 plasminogen activator inhibitor 1, PDGF platelet-derived growth factor, PED pigmented epithelial detachment, RPE retinal pigment epithelium, SRF subretinal fluid, VEGF vascular endothelial growth factor.

Fig. 3. JBI quality score for clinical studies.

The graph shows the quality assessment score in percentage for case reports (CR), case-control (CC), case series (CS), cohort (Ch) studies, cross-sectional (CrS) studies, and randomized controlled trial (RCT). The mechanism of each study is colour coded as shown in the figure legend. MR mineralocorticoid receptors, JBI Joanna Briggs Institute.