Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome

Highlights

  • •

    Ciliochoroidal effusion was present in 60% of eyes with peripapillary pachychoroid syndrome.

  • •

    Eyes with PPS demonstrated increased nasal and temporal scleral thickness compared with controls.

  • •

    Regional scleral alterations may contribute to structural changes within the pachychoroid spectrum.

Purpose

To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls.

Design

Retrospective cross-sectional study

Methods

A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P <.010)

Results

The mean age of PPS patients was 75.6 ± 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 ± 74.97 µm vs 331.13 ± 62.65 µm: P =.007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls ( P <.001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion ( P <.05).

Conclusion

Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

INTRODUCTION

P eripapillary pachychoroid syndrome (PPS) is a recently described retinal condition included in the so-called pachychoroid disease spectrum (PDS), a group of disorders characterized by reduced fundus tessellation, dilated choroidal vessels in Haller’s layer—referred to as pachyvessels —with thinning of the overlying inner choroid and choroidal hyperpermeability demonstrated by indocyanine green angiography. , Although a subfoveal choroidal thickness (SFCT) greater than 300 µm is frequently cited as a reference value for pachychoroid, no universally accepted quantitative cutoff exists. ,, Healthy eyes display considerable variation in choroidal thickness, influenced by several factors including age, axial length, and diurnal variations. Consequently, accurate diagnosis of PDS requires integration of both quantitative measurements and qualitative multimodal imaging findings.

The etiopathogenesis of PDS is still under debate. The most widely accepted explanation is the “multi-hit theory,” which suggests that in anatomically predisposed eyes, triggering factors can lead to the development of retinal alterations. This framework builds upon earlier concepts, including the “two-hit theory” proposed by Hirooka et al., which first suggested that imbalanced choroidal circulation in predisposed eyes may require a secondary insult to manifest clinically. Among the proposed predisposing anatomical factors—such as reduced axial length and asymmetric drainage of the vortex veins—qualitative or quantitative alterations of the sclera have also been suggested. In this context, recent evidence has demonstrated increased scleral thickness in eyes with central serous chorioretinopathy (CSC), supporting the hypothesis that scleral structural characteristics may contribute to impaired venous outflow and disease development. Furthermore, CE has been reported in nearly 20% of CSC eyes, indicating that a thickened sclera—similar to the pathological findings in uveal effusion syndrome (UES)—may disrupt choroidal venous drainage and reduce transscleral fluid outflow. ,

Compared with other PDS conditions, PPS is characterized by an older patient age and pachychoroid features surrounding the optic nerve, particularly in the nasal macular region, along with the presence of intraretinal and/or subretinal fluid in this area, occasionally accompanied by optic nerve edema. Common associated findings include a crowded optic nerve head (ONH), hyperopia, short axial length, and choroidal folds. , Unlike CSC, PPS responds less favorably to photodynamic therapy (PDT), and alternative approaches—such as anti–vascular endothelial growth factor (anti-VEGF) therapy, topical corticosteroids, and micropulse laser—have been explored. , These differences in therapeutic response support the concept of PPS as a distinct clinical variant within the PDS, with overlapping but unique pathophysiological mechanisms.

Venous congestion and reduced transscleral fluid outflow have been proposed as potential pathogenetic mechanisms in PPS. However, to date, no studies have evaluated scleral thickness in patients with PPS, nor has the prevalence of CE been systematically assessed in this population. We hypothesize that PPS eyes would demonstrate increased anterior scleral thickness and a higher prevalence of CE compared with controls, supporting a scleral-driven mechanism in PPS. Therefore, the main objective of the present study was to measure anterior scleral thickness in eyes with PPS using anterior segment optical coherence tomography (AS-OCT) and to compare these measurements with those of age-matched healthy controls. In addition, we qualitatively assessed the presence of CE in this cohort of patients.

METHODS

STUDY POPULATION

This retrospective, cross-sectional study was approved by the Institutional Review Board of the University of Bologna and conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all participants after a full explanation of the study protocol. The study received ethical approval from the Ethics Committee of Bologna, Italy (Code CE: 53/2025/Oss/AOUBo). We performed a retrospective chart review of patients diagnosed with PPS who were evaluated at the University of Bologna Hospital between January 2018 and June 2025.

The primary outcome of the study was to assess the difference in anterior scleral thickness between PPS and controls. The secondary outcomes were to assess the prevalence of ciliochoroidal effusion in PPS eyes and to evaluate the association between CE and scleral/choroidal thickness.

PPS was diagnosed according to the following criteria: peripapillary choroidal thickening associated with intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the nasal macula, along with choroidal hyperpermeability, as proposed by Phasukkijwatana et al. The exclusion criteria were the following: (1) other macular diseases, (2) uveitis, (3) glaucoma, (4) a history of systemic conditions associated with PDS (i.e., collagen disease, current pregnancy, organ transplantation, Cushing’s syndrome, and kidney disease), (5) inability to measure scleral thickness accurately because of poor image quality, and (6) previous treatment within the last 12 months. Overall , 40 eyes from 23 patients with a previous diagnosis of PPS were initially identified. After a thorough review of the patients’ clinical history and the evolution of their retinal pathology based on clinical and instrumental findings, 24 consecutive eyes from 14 patients with clinical and instrumental features consistent with a diagnosis of PPS were selected. The diagnosis required agreement between 2 experienced graders (ME, NV), with any discrepancies adjudicated by a third reviewer (MM). Five patients were excluded due to concomitant glaucoma, 3 patients were excluded due to recent surgery within the last 12 months (cataract surgery), and 1 patient due to previous retinal vein occlusion in the same eye. Finally, 20 consecutive eyes from 12 patients were included in the study, as 2 patients chose not to participate in the study protocol. The control group was selected from individuals undergoing ophthalmologic evaluation at our institution during the same study period and consisted of age- and sex-matched subjects with no history of ocular disease and normal findings on comprehensive ophthalmologic examination. The term sex refers to the biological classification of patients as male or female, as recorded in their medical records. All controls demonstrated normal enhanced depth imaging (EDI) OCT with complete absence of PDS features (pachyvessels, inner choroidal attenuation, retinal pigment epithelium abnormalities) or other retinal alterations. Only eyes with high-quality multimodal imaging, including spectral-domain OCT and anterior segment OCT, allowing reliable scleral and choroidal measurements, were included. The same exclusion criteria as for the PPS group were applied to control subjects.

OPHTHALMOLOGICAL ASSESSMENT

PPS patients and healthy controls underwent a comprehensive ophthalmological evaluation, including assessment of refraction, best corrected visual acuity (BCVA) in logMAR (logMAR), biometry (IOL Master 700, Carl Zeiss Meditec AG, Jena, Germany), slit-lamp biomicroscopy, intraocular pressure assessment, and fundoscopy examination. Cross-sectional images of the macular area were obtained using spectral domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Heidelberg, Germany). In PPS eyes, fundus autofluorescence, fluorescein angiography, and indocyanine angiography (ICGA) were performed with a confocal scanning laser ophthalmoscope (Spectralis, Heidelberg Engineering, Heidelberg, Germany). In addition, scleral thickness was measured in both PPS and healthy eyes using the swept source AS-OCT (CASIA 2; TOMEY).

CHOROIDAL THICKNESS MEASUREMENT

Choroidal thickness measurements were performed using EDI OCT images, and the caliper tool provided by the software (Heidelberg Eye Explorer, v1.9.10.0 software; Heidelberg Engineering). Choroidal thickness was defined as the perpendicular distance between the Bruch membrane and the choroidal-scleral junction. The measurement was performed on a horizontal section passing through the central fovea at the following positions: 1) the center of the fovea (subfoveal choroidal thickness or SFCT, 2) 1.500 µm nasal to the foveal center (N1.5), 3) 3.000 µm nasal to the foveal center (N3.0), 4) 1.500 µm temporal to the foveal center (T1.5), 5) 3.000 µm temporal to the foveal center (T3.0), and 6) 250 µm temporal to Bruch membrane origin at the temporal disk margin (BMO250). Images were set to an aspect ratio of 1:1 mm before each measurement. The hyporeflective band corresponding to the suprachoroidal space, when present, was not included in the choroidal thickness measurement. If the choroidal scleral junction was not clearly identified, brightness and contrast of the image were adjusted, using the built-in adjustment tool, to best visualize this junction, and the outer choroidal border was identified by the line connecting the outer margin of the large choroidal vessel layer. Two independent trained graders (M.E. and L.A.) performed all the measurements. The measurements from the first grader (M.E.) were used for statistical analysis, whereas measurements from the second grader (L.A) were used to assess the inter-grader reliability.

ANTERIOR SCLERA THICKNESS MEASUREMENT

For the acquisition of cross-sectional images of the sclera, we referred to the method utilized by Imanaga et al. Using a swept source AS-OCT (CASIA 2; TOMEY), we detected the 4 rectus muscles (superior rectus muscle, lateral rectus muscle, inferior rectus muscle, and medial rectus muscle) as low reflective bands. Accordingly, we measured scleral thickness 6 mm posterior to the scleral spur in 4 directions (superior, temporal, inferior, and nasal) by identifying each rectus muscle with AS-OCT. The AS-OCT scans were performed in parallel with each rectus muscle with a range of 16 mm in diameter. The raster scan mode, consisting of 16 B-scans in a width of 4 mm, was applied to pass precisely through the center of each rectus muscle. After image acquisition, we determined the anterior scleral boundary between each rectus muscle with low reflectivity and the sclera with high and solid reflectivity. We also identified the posterior scleral boundary from the signal originating from the choroid. Scleral thickness was measured vertically 6 mm posterior to the scleral spur as the distance between the anterior and posterior scleral boundaries at 4 locations in total under each rectus muscle. Two independent graders performed the analysis. The measurements from the first grader (M.E.) were used for statistical analysis, whereas measurements from the second grader (L.A) were used to assess the inter-grader reliability. Figure 1 illustrates the technique used to measure anterior scleral thickness.

FIGURE 1

Anterior scleral thickness measurement. Cross-sectional images of the sclera in 4 directions obtained with anterior segment OCT in a healthy patient. Scleral thickness is measured vertically, 6 mm posterior to the scleral spur. A line is traced from the scleral spur to the external wall of the sclera, corresponding to the site of muscle insertion, and the thickness of the sclera is measured manually. The eye was positioned in vertical and horizontal gaze to allow image acquisition. The scleral thickness at the nasal (A) point was 478 µm, at the superior (B) point was 283 µm, at the temporal (C) point was 237 µm, and at the inferior (D) point was 217 µm.

CILIOCHOROIDAL EFFUSION EVALUATION

The analysis of the anterior suprachoroidal space was performed using AS-OCT. Patients were asked to fixate successively on 4 cardinal directions (i.e., up, down, medial, and lateral) using internal fixation lights. Scans were then acquired over the sclera at 4 locations (3, 6, 9, and 12 o’clock), resulting in a total of 4 scans per patient.

The scans were obtained using the BLEB raster preset, which consists of 64 raster scans with 256 A-scans per line and a scanning volume of 12 mm (length) × 12 mm (width) × 11 mm (depth). To standardize the scan location, the scan window was centered at the limbus, with the length of the scanning rectangle oriented perpendicular to the limbal line.

The qualitative analysis of the obtained scans was performed according to the method proposed by Chansangpetch S et al., in which 5 grades of CE severity were defined based on the continuity and height of the signal, as summarized in Table 1 . All cross-sectional images from volumetric scans at each location were reviewed for the presence of hyporeflective signals. If the hyporeflective signal did not have a skip pattern, it was classified based on its height relative to the scleral thickness at the cross-sectional image that had the most prominent effusion. All scans were graded by a single operator (M.E.) and revised by a second operator (N.V). The diagnosis required agreement between 2 experienced graders (ME, NV), with any discrepancies adjudicated by a third reviewer (MM).

TABLE 1

Severity Grading Scale of Anterior Ciliochoroidal Effusion Analyzed Using AS OCT.

Grade Ciliochoroidal Effusion
Grade 0: No visualized hyporeflective signal
Grade 1: Hyporeflective slit in localized, discontinuous, or skip patterns
Grade 2: Continuous hyporeflective slit
Grade 3: Continuous hyporeflective band of less than half of the maximum scleral thickness
Grade 4: Continuous hyporeflective band of at least half of the maximum scleral thickness

STATISTICAL ANALYSIS

Demographic and clinical characteristics were summarized using descriptive statistics, with appropriate measures of central tendency and variability according to variable type (categorical or continuous). The normality of continuous variables was assessed using the Shapiro–Wilk test, and parametric tests were subsequently applied. Associations between categorical variables were evaluated using Fisher’s exact test. Independent samples t-tests were used to compare demographic characteristics between PPS patients and control subjects. The inter-rater reliability was measured by the absolute agreement model of the intraclass correlation coefficient (ICC) for scleral and choroidal thickness measurements. Inter-rater agreement for ciliochoroidal effusion grading was assessed using Cohen’s weighted kappa (κ) coefficient, which accounts for the ordinal nature of the 5-grade classification scale. Comparisons of choroidal and scleral parameters were performed using linear mixed-effects models including group (controls vs PPS) as a fixed effect, axial length as a covariate, and subject as a random effect to account for inter-eye correlation. This model was used to account for inter-eye correlation, addressing the nonindependence of bilateral measurements. For multiple comparisons involving the scleral and choroidal thickness measurements, Bonferroni correction was applied. For scleral thickness comparisons (overall and 4 quadrants), the corrected threshold was P <.010. For choroidal thickness locations, the corrected threshold was P <.0083.Pearson’s correlation coefficient was used to assess relationships between demographic variables and scleral and choroidal parameters. A P -value <.05 was considered statistically significant. All analyses were conducted using IBM SPSS Statistics version 26 (IBM Corp., Chicago, IL, USA).

RESULTS

DEMOGRAPHIC DATA

A total of 20 eyes of 12 patients with PPS (PPS group) and 30 eyes of 15 control patients (control group) were included in the analysis. Demographic data are summarized in Table 2 . The differences between the 2 groups regarding axial length and BCVA were statistically significant. No significant differences were found in age, sex, and pseudophakic condition between the 2 groups. Among the PPS group, 7 eyes received previous treatment (6 eyes received previous anti-VEGF injections, and 1 eye received previous PDT). The mean time from the last treatment and the ophthalmological assessment was 17 ± 3 months. At the time of ophthalmological assessment, each eye presented persistence of subretinal fluid in the macula.

TABLE 2

Demographic Data.

Patients Controls (n = 15) PPS (n = 12) P -Value
Age (years), mean ± SD 78.2 ± 6.4 75.6 ± 9.8 .643
Female, n (%) 2 (13%) 2 (16%) .532
Eyes Controls (n = 30) PPS (n = 20) P -Value
Pseudophakia, n (%) 16 (53.3%) 11 (55%) .876
BCVA (logMAR), mean ± SD 0.1 ± 0.1 0.6 ± 0.3 <.001
Axial length (mm) 23.79 ± 0.81 mm 22.92 ± 0.81 mm .001

PPS = peripapillary Pachychoroid syndrome; BCVA = best corrected visual acuity.

Values in bold are statistically significant.

COMPARISON OF SCLERAL AND CHOROIDAL THICKNESS BETWEEN PPS AND CONTROLS

Patients with PPS showed a significant increase in scleral thickness in the temporal and nasal sectors compared to healthy controls, whereas no differences were observed in the superior and inferior sectors. After Bonferroni correction (corrected threshold P <.010), the temporal scleral thickness remained significant ( P =.007), while nasal thickness showed a trend ( P =.017). In addition, PPS eyes showed a significant increase in choroidal thickness in each sector ( P <.001). After Bonferroni correction (corrected threshold P <.0083), the results remained statistically significant. Axial length was included as a covariate in the linear mixed-effects model to account for its effect on scleral and choroidal thickness. See results in Table 3 . Overall, the measurements by both readers showed a good level of agreement, ICC = 0.886 (95% CI, 0.834–0.942). When we correlated scleral thickness and choroidal thickness in different sectors in PPS eyes and controls, we did not find any significant correlations. See Supplementary Table 1. A representative case of PPS patients is shown in Figure 2 .

TABLE 3

Scleral and Choroidal Thickness in the PPS Group and in the Control group.

Scleral Thickness Controls PPS P -Value
Overall, mean ± SD 356.09 ± 44.47 µm 409.37 ± 72.28 µm .436
Superior, mean ± SD 344.04 ± 68.7 µm 371.92 ± 96.8 µm .612
Inferior, mean ± SD 377.23 ± 67.5 µm 388.64 ± 116 µm .905
Temporal, mean ± SD 331.13 ± 62.65 µm 396.85 ± 74.97 µm .007
Nasal, mean ± SD 388.18 ± 69.21 µm 479.33 ± 116.76 µm .017
Choroidal Thickness
BMO 250 62.57 ± 31.95 µm 164.80 ± 58.33 µm <.001
N3 155.76 ± 57.97 µm 228.80 ± 82.10 µm <.001
N1.5 156.84 ± 42.24 µm 403.90 ± 113.70 µm <.001
SFCT 150.56 ± 58.62 µm 414.85 ± 144.84 µm <.001
T1.5 133.52 ± 55.07 µm 340.31 ± 128.89 µm <.001
T3 103.00 ± 49.89 µm 272.22 ± 110.49 µm <.001
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Sep 19, 2026 | Posted by in OPHTHALMOLOGY | Comments Off on Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome

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