The role of inflammation in central serous chorioretinopathy: From mechanisms to therapeutic prospects

Abstract

Central serous chorioretinopathy (CSC) is a leading cause of permanent vision loss, ranking fourth among macular diseases, trailing only age-related macular degeneration, diabetic retinopathy, and retinal vein obstruction. While mounting evidence implicates inflammation as a pivotal factor in the onset and advancement of CSC, the specific pathophysiological process and molecular mechanisms underlying inflammation remain incompletely understood. A complex network of cytokines, chemokines, and adhesion molecules interplay to trigger inflammatory and pathological cascades, highlighting the need for a comprehensive comprehension of the inflammation-related mechanisms behind CSC progression. In this piece, we examine the existing comprehension of CSC's pathology and pathogenesis. Additionally, we present an overview of the mechanisms underlying the onset and progression of CSC inflammation, followed by a thorough analysis and discussion of the potential of targeted inflammatory intervention for both preventing and treating CSC.

Keywords: central serous chorioretinopathy; chemokines; cytokines; inflammation; therapy.

FIGURE 1

A 38-year-old Arabic male presented with a 2-month history of reduced vision in his right eye (visual acuity right 6/9.5, left 6/7.5). (A) A circular blister of subfoveal fluid is seen at the macula (VISUCAM^® 500, Carl Zeiss Meditec AG). (B) A circle of autofluorescent changes is seen in the area of subretinal fluid. This is hyperautofluorescent on the temporal side, and hypoautofluorescent on the nasal side. (C) Fundus fluorescein angiography shows a single spot of hyperfluorescent leakage (“inkspot”) just superior to the fovea. (D) Indocyanine green angiography shows a larger area of hyperfluorescence superonasal to the fovea. (E) Enhanced depth imaging optical coherence tomography (SPECTRALIS^® HRA + OCT, Heidelberg Engineering Inc.) shows a subfoveal fluid with a thickened choroid (553 microns). Reprinted with permission from Fung et al. (2023). Central serous chorioretinopathy: A review. Clin Exp Ophthalmol. 10.1111/ceo.14201.

FIGURE 2

A 63-year-old Caucasian male truck driver presented with poor vision in his left eye over 20  years (visual acuity right eye 6/6, left eye 6/6). He described metamorphopsia, poor stereopsis and monocular diplopia. (A and F) Colour fundus photos show bilateral retinal pigment epithelial changes in both eyes (VISUCAM^® 500, Carl Zeiss Meditec AG). (B and G) These correspond to areas of stipple autofluorescence. There is a patch of hypoautofluorescence nasal to the left macula due to atrophy. (C and H) Fundus fluorescein angiography shows bilateral hyperfluorescent window defects in both eyes. (D and I) Mid-phase indocyanine green angiography shows bilateral hypercyanesence due to choroidal hyperpermeability. (E) Enhanced depth imaging optical coherence tomography (EDI-OCT, SPECTRALIS^® HRA + OCT, Heidelberg Engineering Inc.) of the right macula shows some pachydrusen, irregularity of the ellipsoid zone and a thickened choroid (subfoveal choroidal thickness of 503 microns) with pachyvessels in Haller’s layer. (J) EDI-OCT of the left macula shows a slick of subretinal fluid and ellipsoid zone loss nasal to the fovea, tiny pigment epithelial detachments nasal and temporal to the fovea, a thickened subfoveal choroidal thickness of 501 microns and pachyvessels. Reprinted with permission from Fung et al. (2023). Central serous chorioretinopathy: A review. Clin Exp Ophthalmol. 10.1111/ceo.14201.

FIGURE 3

Pathogenesis of central serous chorioretinopathy. A proposed pathogenic pathway for development of central serous chorioretinopathy. Pathology does not necessarily occur in a step-by-step linear fashion. The pathogenesis is likely to be multifactorial with feedback processes (Fung et al., 2023).

FIGURE 4

Immune regulation in CSC. Arrows indicate elevated levels or increased activity.

FIGURE 5

Molecular pathophysiological mechanisms causing serous retinal detachment, pigment epithelial detachment, and choroidal neovascularization in CSC. The upstream mechanisms leading to choroid hyperpermeability include vortex vein compression, corticosteroid receptor activation, and oxidative stress/inflammation.