Pachysclera and Ciliochoroidal Effusion in Peripapillary Pachychoroid Syndrome: New AS-OCT Findings

This retrospective, cross-sectional comparative study assessed anterior scleral thickness and ciliochoroidal effusion (CE) in 20 eyes from 12 patients with peripapillary pachychoroid syndrome (PPS) and 30 eyes from 15 healthy controls. PPS eyes demonstrated significantly greater temporal scleral thickness (396.85 ± 74.97 vs 331.13 ± 62.65 μm; P = .007), while CE was detected in 60% of PPS eyes and none of the controls (P < .001). PPS eyes with CE also showed greater mean scleral and subfoveal choroidal thickness. The findings support a potential association between scleral anatomy and PPS, but the small, single-center, cross-sectional study cannot establish causality.

Peripapillary pachychoroid syndrome (PPS) is a condition within the pachychoroid disease spectrum, characterized by pachychoroid features around the optic nerve, particularly in the nasal macular region, often accompanied by intraretinal fluid (IRF) and/or subretinal fluid (SRF). Other reported features include a crowded optic nerve head, hyperopia, short axial length, and choroidal folds.

Venous congestion and reduced transscleral fluid outflow have been proposed as possible mechanisms in PPS. However, anterior scleral thickness and the prevalence of ciliochoroidal effusion had not been systematically assessed in this population. The investigators hypothesized that PPS eyes would show increased anterior scleral thickness and a higher prevalence of CE than healthy controls.

Primary objective: Compare anterior scleral thickness in PPS eyes and age-matched healthy controls using anterior segment optical coherence tomography (AS-OCT).

Secondary objectives: Assess the prevalence of CE in PPS and examine its association with scleral and choroidal thickness.

• Design: Retrospective, cross-sectional, comparative study.
• Setting: University of Bologna Hospital, Italy; clinical records from January 2018 through June 2025.
• Study group: 20 eyes from 12 patients with PPS.
• Control group: 30 eyes from 15 age- and sex-matched healthy subjects.
• Mean age: 75.6 ± 9.8 years in the PPS group and 78.2 ± 6.4 years in controls (P = .643).
• Female participants: 2 of 12 (16%) in the PPS group and 2 of 15 (13%) in controls.

Initially, 40 eyes from 23 patients with a previous PPS diagnosis were identified. After review and application of eligibility criteria, 24 eyes from 14 patients were selected; exclusions included concomitant glaucoma, recent cataract surgery, and previous retinal vein occlusion. Two patients did not participate, leaving 20 eyes from 12 patients in the final PPS group.

PPS diagnosis required peripapillary choroidal thickening associated with IRF and/or SRF in the nasal macula, together with choroidal hyperpermeability as described in the cited diagnostic framework. Two experienced graders agreed on the diagnosis, with discrepancies adjudicated by a third reviewer. Eyes with other macular diseases, uveitis, glaucoma, specified systemic conditions associated with PDS, inadequate image quality, or treatment within the preceding 12 months were excluded.

All participants underwent comprehensive ophthalmic assessment, including refraction, best-corrected visual acuity (BCVA), optical biometry, slit-lamp examination, intraocular pressure measurement, and fundus examination.

• Macular imaging: Spectral-domain OCT with enhanced depth imaging (EDI-OCT) was used to measure choroidal thickness.
• Anterior scleral imaging: Swept-source AS-OCT (CASIA 2; TOMEY) was used to measure anterior scleral thickness.
• Additional PPS imaging: Fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were performed in PPS eyes.
• Choroidal measurement sites: Subfoveal choroidal thickness (SFCT), 1.5 mm and 3.0 mm nasal to the fovea (N1.5 and N3.0), 1.5 mm and 3.0 mm temporal to the fovea (T1.5 and T3.0), and 250 μm temporal to the temporal border of Bruch membrane opening (BMO250).
• Scleral measurement sites: Four quadrants—superior, temporal, inferior, and nasal—at 6 mm posterior to the scleral spur.

Two independent graders performed thickness measurements. The first grader’s measurements were used for the statistical analysis, while the second grader’s measurements were used to assess inter-grader reliability.

AS-OCT detected CE in 12 of 20 PPS eyes (60%). No CE was observed in the 30 healthy control eyes (P < .001). Effusion was bilateral in 6 eyes/patient cases and unilateral in 6 cases, as reported by the authors.

• Most frequently involved sector: Superior, 11 cases.
• Temporal sector: 10 cases.
• Inferior sector: 7 cases.
• Nasal sector: 7 cases.

Sector counts are not mutually exclusive. The superior sector included 8 grade-1, 2 grade-2, and 1 grade-3 findings. The temporal sector included 6 grade-1, 3 grade-2, and 1 grade-3 findings. The inferior sector included 3 grade-1 and 4 grade-2 findings. The nasal sector included 3 grade-1 and 4 grade-2 findings.

CE was graded on a five-level AS-OCT scale: grade 0, no visible hyporeflective signal; grade 1, localized/discontinuous or skip-pattern hyporeflective slit; grade 2, continuous hyporeflective slit; grade 3, continuous hyporeflective band less than half the maximum scleral thickness; and grade 4, continuous hyporeflective band at least half the maximum scleral thickness. Inter-grader agreement for CE grading was excellent (weighted κ = 0.88; 95% CI, 0.79–0.95).

PPS eyes showed greater mean scleral thickness values in several quadrants, but the statistically significant between-group difference after the study’s Bonferroni correction was in the temporal quadrant.

• Overall scleral thickness: 409.37 ± 72.28 μm in PPS vs 356.09 ± 44.47 μm in controls; P = .436 (not statistically significant).
• Temporal quadrant: 396.85 ± 74.97 μm vs 331.13 ± 62.65 μm; P = .007 (statistically significant after correction).
• Nasal quadrant: 479.33 ± 116.76 μm vs 388.18 ± 69.21 μm; P = .017 (numerically higher, but did not meet the corrected threshold of P < .010).
• Superior quadrant: 371.92 ± 96.8 μm vs 344.04 ± 68.7 μm; P = .612.
• Inferior quadrant: 388.64 ± 116 μm vs 377.23 ± 67.5 μm; P = .905.

Therefore, the study does not demonstrate uniform or overall statistically significant scleral thickening in PPS. Its principal scleral finding is regional, with significant temporal thickening and a nonsignificant trend toward greater nasal thickness.

Choroidal thickness was significantly greater in PPS eyes than in controls at all six measured locations (all P < .001, remaining significant after Bonferroni correction).

• SFCT: 414.85 ± 144.84 μm in PPS vs 150.56 ± 58.62 μm in controls.
• N1.5: 403.90 ± 113.70 μm vs 156.84 ± 42.24 μm.
• N3.0: 228.80 ± 82.10 μm vs 155.76 ± 57.97 μm.
• T1.5: 340.31 ± 128.89 μm vs 133.52 ± 55.07 μm.
• T3.0: 272.22 ± 110.49 μm vs 103.00 ± 49.89 μm.
• BMO250: 164.80 ± 58.33 μm vs 62.57 ± 31.95 μm.

Within the PPS group, eyes with CE had greater values than eyes without CE for selected parameters:

• Mean scleral thickness: 414.81 ± 69.26 μm with CE vs 367.39 ± 70.22 μm without CE; P = .048.
• Inferior scleral thickness: 413.90 ± 104.22 μm vs 326.50 ± 67.12 μm; P = .039.
• N1.5 choroidal thickness: 435.00 ± 99.38 μm vs 335.42 ± 116.41 μm; P = .034.
• SFCT: 454.41 ± 124.28 μm vs 331.42 ± 157.75 μm; P = .026.

Other comparisons in the CE subgroup table were not statistically significant. These subgroup P values are reported as presented in the article; the authors characterize the associations as preliminary.

The findings are consistent with the hypothesis that scleral anatomy may contribute to PPS susceptibility or phenotype. The authors discuss two proposed pathways by which a thickened or less compliant sclera might affect choroidal fluid dynamics:

• Impaired vortex vein outflow: Increased scleral thickness or rigidity may compress the intrascleral course of vortex veins, increase resistance to venous drainage, and contribute to choroidal congestion.
• Reduced transscleral fluid egress: Reduced scleral permeability or fluid outflow may favor fluid accumulation within the outer choroid or suprachoroidal space.

The regional pattern of scleral thickening may reflect biomechanical heterogeneity. However, the study did not directly assess vortex vein morphology, intervortex anastomoses, choroidal vascular congestion, or transscleral fluid transport. These mechanisms remain hypotheses rather than demonstrated explanations.

The authors also note that CE may be a morphological indicator associated with greater scleral and choroidal thickness, and potentially with disease severity. This interpretation is preliminary and does not establish CE as a validated prognostic biomarker.

• Consider anterior segment OCT as an additional structural assessment: In PPS, AS-OCT can identify suprachoroidal hyporeflective spaces consistent with CE and permit sectoral assessment of anterior scleral thickness.
• Pay attention to regional rather than only global measurements: The significant between-group scleral finding was temporal. Overall mean scleral thickness was not significantly different, so a global measurement alone may obscure regional variation.
• Interpret CE alongside posterior-segment findings: In this cohort, CE was associated with greater mean scleral and subfoveal choroidal thickness. It may provide additional morphological context, but should not be used alone to grade disease severity or determine treatment.
• Account for axial length and baseline group differences: PPS eyes had shorter axial length (22.92 ± 0.81 vs 23.79 ± 0.81 mm; P = .001) and worse mean BCVA (0.6 ± 0.3 vs 0.1 ± 0.1 logMAR; P < .001). The mixed-effects models included axial length as a covariate.
• Do not infer causation: The cross-sectional design cannot determine whether scleral thickening precedes PPS, results from chronic choroidal congestion, or reflects a shared anatomical predisposition.
• Avoid changing treatment based on these findings alone: The study evaluated anatomy and imaging associations, not treatment efficacy or clinical outcomes from an intervention.

Strengths

• Use of both EDI-OCT and AS-OCT to evaluate posterior choroidal and anterior scleral structures.
• Assessment of four scleral quadrants and multiple predefined choroidal locations.
• Independent graders and reported inter-grader reliability for thickness measurements (ICC = 0.886; 95% CI, 0.834–0.942) and CE grading (weighted κ = 0.88; 95% CI, 0.79–0.95).
• Linear mixed-effects models accounted for correlation between two eyes from the same participant, with axial length included as a covariate.

Limitations

• Small sample: 20 PPS eyes from 12 patients and 30 control eyes from 15 subjects.
• Retrospective, cross-sectional design, which cannot establish temporal relationships or causality.
• Single-center tertiary referral population, potentially introducing selection bias toward more severe PPS phenotypes.
• Both eyes from some participants were included; although mixed models accounted for inter-eye correlation, the effective sample size remains limited by the number of individuals.
• ICGA was performed only in PPS eyes, not controls, so subclinical pachychoroid features in controls cannot be completely excluded.
• Scleral thickness was measured manually at 6 mm posterior to the scleral spur, rather than directly at the vortex veins; no automated commercial measurement software was available.
• The study did not directly evaluate vortex vein morphology, choroidal vascular congestion, or scleral biomechanical properties.
• The observed CE associations and possible relationship with disease severity require confirmation in larger prospective cohorts.

Conclusion: In this small cross-sectional study, PPS eyes demonstrated significantly greater temporal anterior scleral thickness and a high prevalence of ciliochoroidal effusion compared with healthy controls. CE was associated with greater mean scleral thickness, inferior scleral thickness, N1.5 choroidal thickness, and SFCT. These findings support further investigation of scleral anatomy and suprachoroidal fluid spaces in PPS, but remain hypothesis-generating rather than proof of a scleral cause or a validated clinical biomarker.