Purpose
To compare choroidal layer thickness beneath flat irregular pigment epithelial detachments (PEDs) between uncomplicated chronic central serous chorioretinopathy (uCSC) and CSC complicated by type 1 macular neovascularization (cCSC).
Design
Retrospective cross-sectional study.
Methods
This retrospective study included 94 treatment-naïve eyes (45 uCSC, 49 cCSC) with flat irregular PEDs. Using swept-source optical coherence tomography, we measured choriocapillaris-Sattler layer complex thickness and Haller’s layer thickness beneath the PEDs. Measurements were performed in the central segments of three equal divisions under each PED.
Results
Mean Sattler layer complex thickness was significantly lower in cCSC compared to uCSC (47.2 ± 18.6 µm vs 81.4 ± 22.4 µm, P = .002). Similarly, Haller’s layer thickness was reduced in cCSC (265.3 ± 45.8 µm vs 334.5 ± 43.2 µm, P = .008). Other characteristics, including age (56.1 ± 7.9 vs 54.3 ± 8.4 years, P = .28), disease duration (11.2 ± 3.1 vs 8.4 ± 2.6 months, P = .08), and PED dimensions were comparable between groups.
Conclusions
cCSC eyes show significant thinning of both the choriocapillaris-Sattler complex and Haller’s layer under flat irregular PEDs compared to uCSC eyes. These findings suggest that progressive choroidal thinning may be a key feature of neovascular transformation and could serve as a potential biomarker to identify eyes at risk for neovascular complications.
INTRODUCTION
C entral serous chorioretinopathy (CSC) is characterized by serous retinal detachment and various retinal pigment epithelium (RPE) alterations, including a specific phenotype of flat irregular pigment epithelial detachments (FIPEDs). , These shallow, irregular RPE elevations have gained increasing attention as they may harbor type 1 macular neovascularization (MNV), representing a critical diagnostic and therapeutic challenge.
The distinction between FIPEDs with and without underlying MNV in CSC patients remains particularly challenging, as both entities can sometimes present with similar morphological features on conventional imaging. Recent studies have demonstrated that up to 40% of chronic CSC patients with FIPEDs may develop MNV, significantly impacting disease management and visual outcomes.
Swept-source optical coherence tomography angiography (SS-OCTA) has emerged as a valuable tool for detecting MNV within FIPEDs. However, the underlying choroidal changes that might predispose to or indicate neovascularization remain poorly understood. The enhanced penetration and resolution capabilities of SS-OCT technology facilitate the detailed visualization and measurement of distinct choroidal layers beneath these FIPEDs, including the choriocapillaris-Sattler layer complex and Haller’s layer.
A comprehensive understanding of the relationship between choroidal layer alterations beneath FIPEDs and the presence of MNV could offer significant insights into the disease pathogenesis. Furthermore, such understanding could potentially result in the identification of new biomarkers for the early detection of MNV. Previous studies have demonstrated altered choroidal blood flow and thickness in CSC patients. , However, a thorough investigation into the specific alterations of the choroidal layers beneath FIPEDs in relation to the presence of MNV remains to be conducted.
The objective of this study was to make a comparison between the thickness of the choroidal layers, with particular attention to the choriocapillaris-Sattler complex and Haller’s layer, in patients with CSC who either have or do not have MNV beneath FIPEDs. The analysis of these differences was undertaken to identify potential choroidal architectural changes that could be associated with or that might predispose to the development of MNV in these challenging cases.
METHODS
STUDY PARTICIPANTS
This retrospective study was conducted at the medical retina clinic of the Department of Translational Biomedicine Neuroscience at the Aldo Moro University in Bari, Italy. We conducted a comprehensive review of our electronic medical record system to identify all patients diagnosed with chronic CSC between January 2023 and January 2024. From an initial pool of 142 patients, we applied our inclusion/exclusion criteria, resulting in the final cohort of 94 eligible patients. This systematic screening approach ensured a representative sample of treatment-naïve CSC patients with flat irregular PEDs for our comparative analysis. The study was conducted in accordance with the tenets of the Declaration of Helsinki. As per Italian regulations for retrospective studies, formal approval from an ethics committee was not required, but the institutional ethics committee was informed about the study.
Inclusion criteria were: (1) age ≥18 years, (2) diagnosis of uCSC with and without MNV confirmed by fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCTA, (3) presence of active disease characterized by subretinal fluid on structural OCT, (4) presence of shallow irregular PED appearing as a low-lying, undulating elevation of the RPE on structural OCT, (5) best-corrected visual acuity (BCVA) of 20/400 or better, and (6) right eye was selected when both eyes met the inclusion criteria. According to Chhablani’s classification, all included eyes were classified as simple CSC either complicated (cCSC group) or uncomplicated (uCSC group) by type 1 MNV.
Exclusion criteria included: (1) previous ophthalmological surgery, (2) history of any treatment for UCSC including laser therapy, photodynamic therapy, or anti-VEGF injections, (3) systemic steroid use, (4) presence of other retinal disorders including age-related macular degeneration, diabetic retinopathy, or pathologic myopia, (5) pregnancy, and (6) media opacities preventing high-quality imaging acquisition.
Patients were divided into two groups based on the presence or absence of MNV, which was assessed using SS-OCTA performed with the PLEX Elite 9000 device (Carl Zeiss Meditec, Inc.) and confirmed with ICGA.
DISEASE DURATION ASSESSMENT
Disease duration was determined based on comprehensive review of medical records and imaging data. For both uCSC and cCSC, disease duration was calculated from the first documented evidence of serous retinal detachment or symptoms consistent with CSC. All included patients had persistent subretinal fluid for more than 4 months, meeting the criteria for chronic CSC. For patients in the cCSC group, the duration encompassed the entire CSC disease history, including the period before the development of type 1 MNV.
EXAMINATIONS
All patients underwent a complete ophthalmological examination including BCVA measurement using Snellen charts (converted to logMAR for statistical analysis), slit-lamp biomicroscopy, intraocular pressure measurement, and dilated fundus examination.
Multimodal imaging included FA, ICGA, and swept-source OCT/OCTA. FA and ICGA were performed using the Heidelberg Spectralis HRA + OCT (Heidelberg Engineering) to confirm UCSC diagnosis and evaluate choroidal vascular hyperpermeability and RPE dysfunction. Maybe indicate here the time of imaging of the Fa and ICG images.
IMAGE ACQUISITION AND ANALYSIS
All SS-OCT and SS-OCTA images were acquired using the PLEX Elite 9000 device (Carl Zeiss Meditec, Inc.). The imaging protocol consisted of:
1. Structural SS-OCT:
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HD 51-line raster scanning protocol centered on the fovea
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Each B-scan consisted of 1024 A-scans
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Only scans with a signal strength ≥7 were included for analysis
2. SS-OCTA:
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6 × 6 mm scanning area centered on the fovea
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Each scan consisted of 500 A-scans by 500 B-scans
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Two repeated B-scans were acquired at each location
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Motion correction was applied using the device’s built-in software
CHOROIDAL LAYER MEASUREMENTS
Choroidal layer measurements were performed on the HD 5-line raster SS-OCT scans. For each eye, we analyzed:
1. The B-scan showing the highest PED height
2. The B-scan showing the greatest PED width
In each selected B-scan, the following measurements were performed:
1. Total choroidal thickness (CT): measured from the outer border of the RPE/Bruch’s membrane complex to the choroidal-scleral interface
2. Choriocapillaris-Sattler layer complex thickness (SLCCT): measured from the outer border of the RPE/Bruch’s membrane complex to the interface between medium and large choroidal vessels
3. Haller’s layer thickness (HLT): measured from the interface between medium and large choroidal vessels to the choroidal-scleral interface
Under each PED, both the SLCCT complex and HLT layer were divided into three equal segments ( Figures 1-3 ). The mean thickness of the two central segments was calculated to standardize measurements across different PED sizes. All measurements were performed using the device’s built-in caliper tool.
Central macular thickness was automatically calculated by the device’s software.
MNV DETECTION
En-face SS-OCTA 6 × 6-mm volume scans were obtained. The slab between Bruch’s membrane and the RPE was carefully examined for the presence of neovascular networks. In cases where the automatic segmentation did not accurately delineate the RPE detachment, manual adjustment was performed to ensure proper inclusion of the entire MNV within the segmentation. MNV was defined as an abnormal vascular network showing flow signal above the background threshold.
The final diagnosis of MNV was confirmed by correlating SS-OCTA findings with ICGA.
ICGA images were analyzed in three phases: early (0-1 minute) to detect feeder vessels, midphase (5-10 minutes) to evaluate the neovascular network morphology, and late phase (15-20 minutes) to assess network maturity and leakage patterns. Type 1 MNV was identified by the presence of an irregular network with indistinct margins in the early and midphases, with late staining but minimal leakage in the late phase.
EVALUATION OF INTERVORTEX ANASTOMOSES
Intervortex anastomoses were assessed using en-face SS-OCT images. They were defined as nontapering vessels crossing the watershed zone between vortex vein territories, considering vessel asymmetry between upper and lower quadrants.
IMAGE ANALYSIS PROTOCOL
All measurements were performed independently by two experienced readers (PV, GB) who were masked to the clinical data and group assignment. For continuous variables, the mean of the two measurements was used for analysis. In cases where measurements differed by more than 15%, a third reader (FB) performed the measurement, and the median value was used. The intraclass correlation coefficient (ICC) showed excellent agreement between readers (ICC = 0.92).
STATISTICAL ANALYSIS
Statistical analysis was performed using SPSS Statistics (version 27.0; IBM Corp.). The Shapiro-Wilk test was used to verify the normal distribution of continuous variables, which confirmed normal distribution of all data. Descriptive statistics were presented as mean ± standard deviation for continuous variables and as frequencies and percentages for categorical variables. Between-group comparisons for continuous variables were performed using independent samples t test. Categorical variables were compared using chi-square test or Fisher’s exact test when appropriate. Interobserver agreement for choroidal measurements was evaluated using ICC. Statistical significance was set at P < .05, and all tests were two-tailed.
RESULTS
DEMOGRAPHICS
The study included 94 eyes of 94 patients divided into two groups: 45 eyes with uCSC and 49 eyes with cCSC. The mean age was 54.3 ± 8.4 years in the uCSC group and 56.1 ± 7.9 years in the cCSC group ( P = .28). Mean BCVA was 0.22 ± 0.12 logMAR in the uCSC group and 0.30 ± 0.14 logMAR in the cCSC group ( P = .18). The mean axial length was similar between groups (23.8 ± 1.1 mm in uCSC group vs 23.6 ± 1.2 mm in cCSC group; P = .45). Disease duration from symptom onset was 8.4 ± 2.6 months in the uCSC group and 11.2 ± 3.1 months in the cCSC group ( P = .08). Intervortex anastomoses were detected in 20 eyes (44.4%) in the uCSC group and 26 eyes (53.1%) in the cCSC group ( P = .12). All patients presented with subretinal fluid, while intraretinal fluid was observed in 4 eyes (8.9%) in the uCSC group and 7 eyes (14.3%) in the cCSC group ( P = .09). Early nuclear sclerosis (grade 1-2) was present in 12 patients (26.7%) in the uCSC group and 15 patients (30.6%) in the cCSC group ( P = .67). Baseline characteristics of the study population are summarized in Table 1 .
