Abstract / Summary
Purpose To characterize the phenotypic spectrum of mid-phase hyperfluorescent plaques (MPHPs) on indocyanine green angiography (ICGA) in eyes with central serous chorioretinopathy (CSCR) and to evaluate their relationship with corresponding optical coherence tomography (OCT) features. Design Retrospective, observational multicenter cohort study. Subjects Forty eyes of 29 patients, 25 (86.2%) male and 4 (13.8%) female, with CSCR and a median follow-up of 39 months. Methods Imaging features on ICGA and macular OCT were documented at baseline and follow-up. MPHPs were classified into four 'types': 'without-dots', 'with-dots', 'hypo-center' and 'with-leak'. When multiple types coexisted within one plaque, a single mutually exclusive 'stage' was assigned according to the highest-ranking angiographic feature present, ranked by the hierarchical structure of the features on ICGA. Corresponding OCT features at each MPHP site included subretinal fluid (SRF), ellipsoid zone and retinal pigment epithelium (EZ/RPE) irregularity, pigment epithelial detachment (PED), hyperreflective foci (HRF), outer nuclear layer (ONL) thinning, double-layer sign, RPE atrophy, RPE infrared abnormalities, pachyvessels and choroidal thickness. Associations were estimated using generalized estimating equations clustered at the patient level, with correction for multiple comparisons. Transitions between stages and predictors of new leak onset were assessed over follow-up. Main Outcome Measures OCT structural features across MPHP phenotypes. Results A total of 112 MPHPs were present at baseline, of which 92 had a co-registered OCT B-scan. EZ/RPE irregularity was near-universal (82 of 92, 89.1%) and did not differ across stages (odds ratio [OR] 0.75, q = 0.394. SRF showed the strongest gradient across stages, rising to 100% at the 'with-leak' stage (OR 5.34, 95% CI 2.90–9.84; q < 0.001), followed by HRF (OR 1.66; q < 0.001), PED (OR 1.99; q = 0.019) and ONL thinning (OR 1.93; q = 0.039). At the sites where de novo plaques later appeared, EZ/RPE irregularity was already present in 8 of 10 assessable locations, whereas no other structural feature was. The most common transition between stages was from 'with-dots' to 'hypo-center'; plaques at the 'hypo-center' stage were the most stable (78.3%) and showed the lowest rates of progression to a higher stage. Conclusions MPHPs are dynamic imaging features in CSCR, and structural involvement on OCT increases in proportion to the angiographic complexity of the plaque. EZ/RPE irregularity was present in nearly all plaques, preceded their appearance, and did not vary across stages, suggesting that it marks a susceptible feature at the level of plaques. These findings support the role of MPHPs as focal sites of disease activity within the hyperpermeable choroid.