Pathogenesis of Central Serous ChorioRetinopathy and the Link between Choroidal Hyperpermeability and RPE Pump Reversal

Abstract

Purpose: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism. Methods: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) at baseline and after laser therapy. Results: In 3 out of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA. The development of this sign was suggestive of active leakage into the subretinal space displacing overlying subretinal hyperreflective material (SHRM) and suggestive of a reversal of RPE pump function. All six cases were treated with focal laser to directly target the intense leakage points with remarkable resolution of the fluid due to destruction of the RPE cells mediating reversal of pump function. Conclusions: Unlike chronic CSCR in which degenerative changes of the RPE lead to oozing of fluid into the subretinal space, in acute forms of CSCR including bullous CSCR, there are focal leaks of the RPE that actively drive fluid into the subretinal space suggestive of RPE pump reversal. We propose that pachychoroid disease causes increased hydrostatic pressure and increased resistance to the RPE pump thereby triggering a reversal in pump function. Understanding this concept can have therapeutic implications.