Peripapillary pachychoroid syndrome (PPS) is a disease in which the choroid around the optic disc becomes abnormally thickened, leading to exudative changes around the optic disc. It was first reported by Phasukkijwatana et al. in 2018 1, 3).
PPS is considered a subtype of the pachychoroid disease spectrum (PDS) 4). PDS is a group of diseases sharing a common pathological basis of choroidal thickening, pachyvessels (dilated outer choroidal vessels), and thinning of the choriocapillaris, including central serous chorioretinopathy, pachychoroid neovascularization (PNV), and polypoidal choroidal vasculopathy (PCV) 4).
Typical patient profile is elderly male with hyperopia. Peripapillary choroidal folds are present in 77% of cases, and short axial length in 39% 1). Axial length in typical cases is around 22 mm (affected eye 22.3/22.5 mm) 1).
PPS and central serous chorioretinopathy are both subtypes of PDS and share a common pathological basis, but the distribution of lesions differs. In PPS, choroidal thickening and exudation are localized around the optic disc rather than the macula, and intraretinal fluid (IRF) often appears more prominently than subretinal fluid (SRF) 2). In central serous chorioretinopathy, FA shows obvious serous leakage, whereas in PPS, leakage is limited to the peripapillary area.
The main subjective symptom of PPS is slowly progressive visual loss 1). It is not sudden vision loss and often progresses unnoticed. Some patients may also report metamorphopsia (distorted vision).
OCT Findings
Intraretinal fluid (IRF) predominance: In PPS, IRF is often more prominent than SRF 2).
Progression of EZ disruption: Cases have been reported where disruption of the ellipsoid zone (EZ) expands over time 2).
Nasal choroidal thickening: The nasal side is particularly prominent, reaching 431–554 μm in some cases 3).
Peripapillary fibrous proliferation (PFP): This finding is attracting attention as a biomarker for PPS 3).
Imaging and Fundus Findings
Peripapillary choroidal folds: A characteristic finding observed in 77% of cases.
Peripapillary abnormal anastomotic vessels (AVL): Observed as ring-shaped staining on FA 1, 2).
Short axial length and hyperopia: Typical cases have axial lengths around 22 mm with hyperopia 1, 2).
Bilaterality: Many cases show lesions in both eyes.
In PPS, intraretinal fluid (IRF) tends to be more prominent than subretinal fluid (SRF)2). This is thought to be related to collateral circulation pathways from the peripapillary choroidal veins through the prelaminar region, and is a pathophysiologically interesting feature. For details, see the “Pathophysiology” section.
Multiple factors are thought to be involved in the development of PPS.
The diagnosis of PPS requires a combination of multiple imaging tests. Delayed diagnosis or misdiagnosis (especially confusion with branch retinal vein occlusion or central serous chorioretinopathy) is common3).
The characteristics of each imaging test are shown below.
| Examination | Main Findings | Remarks |
|---|---|---|
| EDI-OCT | Increased CT on nasal side of optic disc, IRF, EZ disruption | Most important test3, 4) |
| ICGA | Visualization of pachyvessels and AVL | Evaluation in early phase is useful1, 2) |
| OCTA | Blood flow assessment of choriocapillaris | 97% sensitivity for PDS diagnosis4) |
PPS is often misdiagnosed as the following diseases.
Peripapillary exudation in PPS can resemble the hemorrhage and exudation caused by branch retinal vein occlusion. Indeed, there are reported cases where five doses of aflibercept were ineffective, and the condition was later diagnosed as PPS and resolved with photodynamic therapy3). Confirmation of peripapillary choroidal thickening on EDI-OCT and pachyvessels on ICGA is essential for accurate diagnosis.
The treatment strategy for PPS has not been established, and individualized management is required for each case.
Observation
Spontaneous resolution: Cases of spontaneous resolution within about 3 months have been reported2).
Long-term course: Some cases maintained best-corrected visual acuity (BCVA) of 20/20 over 5 years of untreated observation2).
Indications: First choice when symptoms are mild and vision is preserved. Regular EDI-OCT monitoring is necessary.
Pharmacotherapy
Steroid eye drops: There is a report of starting prednisolone 1% eye drops TID with gradual tapering. Best-corrected visual acuity improved to 20/25 at 3 months, with no recurrence at 9 months1).
Carbonic anhydrase inhibitors (CAI): Dorzolamide eye drops have been used in some cases3).
Mineralocorticoid receptor antagonists (MRA): Eplerenone 25 mg twice daily has been used in some cases3).
Photodynamic therapy
Photodynamic therapy (half-fluence): A report described resolution of exudation at 2 months after half-fluence photodynamic therapy at 25 J/cm²3).
Indications: Considered when drug therapy is ineffective or exudation persists. Efficacy has been reported even in cases unresponsive to anti-VEGF agents3).
Reported administration conditions and outcomes for each treatment are shown below.
| Treatment | Administration method/conditions | Reported outcome |
|---|---|---|
| Prednisolone eye drops | 1% TID → taper1) | Best corrected visual acuity 20/25 at 3 months |
| Eplerenone + dorzolamide | 25 mg BID + eye drops3) | Improvement at 3 months |
| Photodynamic therapy (half-fluence) | 25 J/cm²3) | Resolution at 2 months |
The efficacy of anti-VEGF drugs for PPS has not been established. A case has been reported where five doses of aflibercept were ineffective 3), and their role in PDS in general is considered uncertain 4). When PPS is suspected, it is important to make an accurate diagnosis before relying on anti-VEGF drugs.
The pathology of PPS is explained by a complex mechanism centered on choroidal vascular abnormalities and venous outflow obstruction around the optic disc.
Donvito & Primavera proposed a collateral circulation pathway from the peripapillary choroidal veins through the anterior lamina cribrosa to the central retinal vein (CRV) 2). Increased venous pressure in this pathway is thought to cause an exudative pattern predominantly with intraretinal fluid (IRF).
In the same report, choroidal thickness (CT) showed fluctuations of +33 to +104 μm between workdays and holidays, suggesting that mental and physical stress may influence the pathology of PPS 2). Over the long term, ellipsoid zone (EZ) damage was observed to progress and expand 2).
Cheung CMG et al. proposed a multi-hit theory for PDS in general, including PPS, in which the disease develops when multiple triggers overlap 4). It is thought that genetic predisposition (tendency to form pachyvessels) combined with local and systemic stress factors exceeds the threshold for onset.
Choroidal vortex vein anastomosis is a vascular remodeling finding frequently observed in PDS. In pachychoroid disease, anastomoses crossing the watershed zone have been reported in over 90% of cases 4), and choroidal blood flow dynamics throughout the posterior pole, including the peripapillary area, are thought to be involved in the development of PPS.
In untreated cases followed over time, ellipsoid zone (EZ) disruption has been reported to expand over the course of the disease 2). Although visual acuity may be preserved for a long period (e.g., best-corrected visual acuity maintained at 20/20 for 5 years in one case 2)), attention should be paid to the possibility of irreversible photoreceptor changes.
The efficacy of half-fluence photodynamic therapy for PPS has only been reported in a small number of cases.
Bouzika et al. (2022) reported a case of PPS misdiagnosed as branch retinal vein occlusion and unresponsive to five doses of aflibercept, in which half-fluence photodynamic therapy at 25 J/cm² led to complete resolution of exudation after 2 months 3).
Prospective studies on the mechanism of action of photodynamic therapy for PPS and which patients should be indicated are future challenges 4).
The collateral circulation pathway from the peripapillary choroid to the anterior lamina cribrosa to the central retinal vein, proposed by Donvito & Primavera, is attracting attention as a hypothesis that may explain the pathophysiology of IRF-dominant PPS 2). Future prospective studies using ICGA and OCTA are needed for verification.
Cheung CMG et al. have proposed clarification of disease definition and classification and systematization of biomarkers in PDS 4). The significance of peripapillary fibrous proliferation (PFP) as a biomarker for PPS 3) and the utility of OCTA as a highly sensitive diagnostic tool (sensitivity 97%) 4) are included, and international unification of diagnostic and treatment criteria is a future challenge.
