ICGA Plaques in Central Serous Chorioretinopathy: What OCT Reveals About Activity and Progression

Central serous chorioretinopathy (CSCR) involves choroidal hyperpermeability, RPE dysfunction, and potentially recurrent subretinal fluid (SRF). Mid-phase hyperfluorescent plaques (MPHPs) appear on indocyanine green angiography (ICGA), but their OCT correlates and evolution have been incompletely characterized.

Objective: Classify MPHP phenotypes, map them to OCT findings at the same retinal locations, and examine changes in plaque stage and leakage over time.

• Design: Retrospective, longitudinal, multicenter observational cohort (MICRoN network); imaging obtained between 2013 and 2023.
• Patients: 29 (25 male, 86.2%); eyes: 40; mean age 51.9 ± 8.5 years.
• MPHPs: 112 present at baseline, plus 12 de novo plaques detected at follow-up (124 total).
• Follow-up: Median 39 months (IQR 22.5–53.5); co-registered baseline OCT available for 92/112 plaques.
• Treatment: 25/40 eyes received heterogeneous therapies, including eplerenone, photodynamic therapy, combined therapy, or subthreshold micropulse laser; 15 eyes were observed.

Imaging: Mid-phase ICGA plaques were assessed approximately 5–10 minutes after dye injection and co-registered with spectral-domain OCT. Graders assessed SRF, ellipsoid-zone/RPE irregularity, pigment epithelial detachment (PED), hyperreflective foci (HRF), outer nuclear layer (ONL) thinning, and other chorioretinal findings.

Angiographic stage: Four mutually exclusive stages were assigned using the highest-ranking feature within a plaque: without-dots → with-dots → hypo-center → with-leak. A plaque could simultaneously contain multiple ICGA features; this ordering describes angiographic complexity, not an obligatory temporal sequence.

Statistics: Generalized estimating equations clustered at the patient level assessed plaque–OCT associations. Reported q values account for multiple comparisons.

• Ellipsoid-zone/RPE irregularity: 82/92 plaques (89.1%); not significantly different by stage (OR 0.75; q = 0.394).
• SRF: Present at 41/41 plaques in the with-leak stage; strong stage association (OR 5.34; 95% CI 2.90–9.84; q < 0.001).
• Additional associations: HRF OR 1.66 (q < 0.001); PED OR 1.99 (q = 0.019); ONL thinning OR 1.93 (q = 0.039), per stage increment.
• Structural burden: Mean number of OCT abnormalities increased by 0.62 per stage increment (95% CI 0.42–0.82; P < 0.001).

Interpretive caution: The association of “hypo-center” with SRF was largely explained by coexisting leakage. Choroidal thickness and EZ/RPE irregularity did not show significant gradients across stages.

New plaques: Twelve appeared during follow-up in 5 patients across 6 eyes. At the retinal locations where new plaques emerged, baseline OCT showed EZ/RPE irregularity in 8/10 assessable sites (80%), before an ICGA plaque became visible; no other structural feature was identified at those baseline locations.

This temporal colocalization supports EZ/RPE irregularity as a possible pre-existing susceptibility marker, but does not prove that it causes plaque formation or predict individual progression.

• Stage stability: 61/112 (54.5%) unchanged; 28/112 (25.0%) progressed to a higher stage; 23/112 (20.5%) regressed.
• Common transitions: With-dots → hypo-center (12 plaques); with-leak → hypo-center (13 plaques).
• Hypo-center stability: 18/23 (78.3%) retained their stage; among non-leaking plaques, progression was less frequent from hypo-center than from the two earlier stages (8.7% vs 54.2%; P = 0.0002).
• Leak dynamics: 10/71 (14.1%) initially non-leaking plaques developed leakage; 20/41 (48.8%) initially leaking plaques no longer exhibited leakage at follow-up.

Because imaging was performed at nonuniform intervals and largely compared two time points, these percentages are observed transitions, not annual risks.

For multimodal imaging: An MPHP on ICGA may help localize a focal choroid–RPE area where co-registered OCT reveals structural abnormalities. The “with-leak” stage was the strongest cross-sectional signal of concurrent SRF and greater structural burden.

For monitoring: EZ/RPE changes may precede the angiographic appearance of some new plaques, and a hypo-center appearance may persist after leakage resolves. Consider these as hypotheses that could inform longitudinal image interpretation, not validated prognostic thresholds.

Therapeutic implications: Neither a treatment effect on stage transitions nor a patient-level management benefit was demonstrated. Do not select photodynamic therapy or other treatment solely from MPHP stage based on this study.

Strengths: Multicenter cohort, co-registered ICGA/OCT analysis, patient-clustered statistical models, and longitudinal plaque-level observations.

Limitations: Retrospective design; 29 patients and relatively few plaques in some stages; only 92/112 baseline plaques with co-registered OCT; two principal imaging time points with variable follow-up; treatment recorded per eye rather than plaque; potential residual confounding and limited external validation.

Bottom line: MPHP stage tracks local OCT structural involvement in CSCR, particularly SRF at leakage sites. EZ/RPE irregularity was nearly universal and sometimes preceded visible plaque development. Prospective studies are needed before using plaque stage to predict prognosis or guide treatment.