Pachydrusen
Size: Large deposits >125 µm
Distribution: Scattered and isolated in the posterior pole, with clear borders
Choroid: Haller layer thickening (pachyvessels) + choriocapillaris thinning
Background: Associated with pachychoroid disease
Pachydrusen
Key Points at a Glance
Section titled “Key Points at a Glance”1. What is Pachydrusen?
Section titled “1. What is Pachydrusen?”Pachydrusen are deposits beneath the retinal pigment epithelium (RPE) that belong to the pachychoroid disease spectrum, characterized by choroidal thickening. This concept was proposed by Spaide in 2018 and is thought to have a different pathogenesis from conventional soft drusen.
Pachychoroid disease is a group of disorders based on choroidal vascular abnormalities that cause damage to the outer retina and choriocapillaris. 1) It includes central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), peripapillary choroidal neovascularization (PNV), retinal pigment epithelial detachment (PED), and pachychoroid pigment epitheliopathy (PPE). 1)
As a reference for choroidal thickness in pachychoroid, reports indicate 191–350 µm in healthy eyes, 345–505 µm in central serous chorioretinopathy, and 223–590 µm in polypoidal choroidal vasculopathy. 1) In Japanese patients with neovascular age-related macular degeneration (nAMD), the proportion with drusen is reported to be about 30%. 3)
Q
What is the difference between ordinary drusen and pachydrusen?
A
Soft drusen are known as precursor lesions of age-related macular degeneration, tend to accumulate in the fovea, and are associated with a thin choroid. In contrast, pachydrusen are large deposits that arise in the setting of pachychoroid (choroidal thickening) and are scattered in the posterior pole. Their pathogenesis and associated diseases also differ. 1)
2. Main symptoms and clinical findings
Section titled “2. Main symptoms and clinical findings”Subjective symptoms
Section titled “Subjective symptoms”Pachydrusen alone are usually asymptomatic and are often discovered incidentally. When complications such as polypoidal choroidal vasculopathy or neovascular AMD progress, the following symptoms may occur.
- Metamorphopsia: Objects appear distorted. This occurs when a neovascular membrane or serous retinal detachment develops.
- Visual acuity loss: This becomes prominent when the lesion extends to the fovea.
- Scotoma: May be perceived as a central or paracentral visual field defect.
Clinical Findings
Section titled “Clinical Findings”Pachydrusen are large (diameter >125 µm) yellowish-white sub-RPE deposits scattered in the posterior pole. They have relatively distinct borders, tend to be fewer in number compared to soft drusen, and are often isolated and scattered.
Choroidal findings include thickening and dilation of the Haller layer (outer choroid) (pachyvessels) and thinning of the Sattler layer and choriocapillaris. 1)
The ASHS-LIA (area of stromal hyperfluorescence surrounded by a late wash-in area) finding observed in the late phase of ICGA is seen in approximately 60% of polypoidal choroidal vasculopathy/AT1 cases. 1)
The characteristics of each drusen subtype are shown below.
Soft drusen
Size: Medium to large, >63 µm
Distribution: Clustered at the fovea, indistinct borders
Choroid: Tendency toward atrophy and thinning
Background: Precursor lesion of typical age-related macular degeneration
Pseudo-drusen (SDD)
Size: Variable
Distribution: Located above the RPE (not below the RPE)
Choroid: Associated with thinning
Background: High risk of GA progression
The estimated prevalence of pachydrusen by disease background is shown below.
| Disease | Estimated prevalence |
|---|---|
| Non-exudative age-related macular degeneration | Approximately 11.7% |
| Polypoidal choroidal vasculopathy | 49–56% |
| Central serous chorioretinopathy | 40–60% |
Q
What diseases are pachydrusen commonly associated with?
A
Polypoidal choroidal vasculopathy and AT1 (typical nAMD) show pachydrusen in up to 60% of cases. 1) Central serous chorioretinopathy also has a comorbidity rate of about 40–60%. Pachydrusen are observed at a high frequency across the entire pachychoroid disease spectrum.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”The exact mechanism of pachydrusen formation remains unknown and is still under investigation. Genetically, the ARMS2 risk allele associated with typical age-related macular degeneration is less frequent in pachydrusen and pachychoroid diseases. Additionally, the CFH gene risk allele has been reported to be protective against central serous chorioretinopathy. The CFH gene is also involved in the development of pachychoroid, central serous chorioretinopathy, and PNV. 3)
Choroidal venous congestion is considered a key driver in the core pathogenesis. Vortex vein anastomosis is observed in about 90% of central serous chorioretinopathy, about 95% of PNV, and about 98% of polypoidal choroidal vasculopathy, suggesting that outflow obstruction of the choroidal venous system leads to vasodilation. 2)
A cascade of pathological events has been proposed: dilation of Haller’s layer (pachyvessels) → thinning of Sattler’s layer and choriocapillaris → local ischemia → macular neovascularization (submacular neovascularization). 2)
4. Diagnosis and Examination Methods
Section titled “4. Diagnosis and Examination Methods”The diagnosis of pachydrusen involves a combination of fundus examination, OCT, and EDI-OCT (enhanced depth imaging OCT). 1)
The characteristics of each examination are shown below.
| Examination Method | Findings/Purpose |
|---|---|
| Fundus examination | Confirm large yellowish-white deposits under the RPE at the posterior pole |
| EDI-OCT | Confirm Haller layer thickening and hyperreflective material under the RPE |
| Late-phase ICGA | ASHS-LIA (positive in about 60% of polypoidal choroidal vasculopathy/AT1) |
- EDI-OCT: Visualizes the full thickness of the choroid and evaluates the relative thickness of the Haller layer, Sattler layer, and choriocapillaris. It appears as a homogeneous medium-reflective substance beneath the RPE. 1)
- ICGA (Indocyanine Green Angiography): The late-phase ASHS-LIA pattern is characteristic of pachychoroid disease. It is also essential for identifying polypoidal lesions and is used to differentiate from or confirm the coexistence of polypoidal choroidal vasculopathy. 1)
- OCTA (OCT angiography): Useful for evaluating choriocapillaris flow deficit (CCFD).
Differential Diagnosis
Section titled “Differential Diagnosis”The main differential diagnoses are shown below.
- Soft drusen: Differentiated by central macular clustering, indistinct borders, and choroidal thinning. The boundary between pachychoroid and soft drusen-driven disease may actually be ambiguous in some cases. 1)
- Pseudo-drusen/SDD (subretinal drusenoid deposits): Located above the RPE, showing a punctate pattern on en face OCT.
- RPE detachment (PED): Larger, often with sub-RPE fluid accumulation.
5. Standard Treatment
Section titled “5. Standard Treatment”Currently, there is no established specific treatment for pachydrusen itself. There appears to be no risk of progression to geographic atrophy (GA), and the 5-year rate of progression to nAMD is similar between soft drusen (17.8%) and pachydrusen (17.0%). 1)
Pachydrusen is associated with progression to polypoidal choroidal vasculopathy/AT1 (typical nAMD), but may follow a pathophysiologically different pathway from typical age-related macular degeneration driven by soft drusen. 1) The epiphenomenon hypothesis (pachydrusen is merely a byproduct of pachychoroid disease) has also been proposed, and its role in pathogenesis remains under debate. 1)
When complicated by polypoidal choroidal vasculopathy/nAMD, the treatment strategy is as follows.
- Anti-VEGF therapy: First-line treatment for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Anti-VEGF drugs are also first-line in Japan. 3) Newer agents such as brolucizumab and faricimab are also options. 2)
- Combination with PDT (photodynamic therapy): In polypoidal choroidal vasculopathy, combination therapy with anti-VEGF drugs and PDT may be selected. 3)
- Observation: Pachydrusen alone (without neovascularization or serous changes) is managed with regular follow-up.
Q
Is treatment always necessary for pachydrusen?
A
Pachydrusen alone is usually asymptomatic, and no specific treatment exists. When complications such as polypoidal choroidal vasculopathy or neovascular AMD occur, anti-VEGF therapy or PDT may be selected. Regular monitoring is important.
6. Pathophysiology and Detailed Pathogenesis
Section titled “6. Pathophysiology and Detailed Pathogenesis”In recent years, the central role of choroidal venous congestion in pachychoroid disease has become clear. A pathway has been proposed: outflow obstruction of choroidal veins (vortex veins) → venous congestion → anastomosis formation. 1)
Pachyvessels are dilated outer choroidal vessels (Haller layer vessels) with thin endothelial cell channels, reflecting increased intrachoroidal pressure. 2)
Choroidal Venous Congestion
Vortex vein outlet obstruction: Increased outflow resistance → elevated intrachoroidal pressure
Vortex vein anastomosis: Observed in 90% of central serous chorioretinopathy, 95% of PNV, and 98% of polypoidal choroidal vasculopathy2)
Haller layer dilation: Formation of pachyvessels (thin endothelial cell channels)2)
Inner Choroidal Damage
RPE and outer retinal damage
RPE dysfunction: Impaired disposal of outer segment metabolic waste
ASHS-LIA: Involves neutral lipid accumulation in Bruch’s membrane 1)
Macular neovascularization: Chronic ischemia → increased VEGF production → neovascular sprouting 2)
CCFD (choriocapillaris flow deficit) is visualized as delayed filling on ICGA and flow deficit on OCTA, serving as an indicator for quantitatively evaluating inner choroidal layer damage in pachychoroid disease. 2)
ASHS-LIA (areas of stromal hyperfluorescence surrounded by late wash-in zones) is thought to be associated with neutral lipid accumulation in Bruch’s membrane and is considered a finding reflecting tissue damage in pachychoroid disease. 1)
As a limitation of the definition of “pachychoroid,” defining pachychoroid solely by choroidal thickness (CT) is insufficient, and an integrated assessment of pachyvessels, choriocapillaris thinning, and clinical context is required. 1)
7. Latest Research and Future Perspectives (Research-stage Reports)
Section titled “7. Latest Research and Future Perspectives (Research-stage Reports)”Definition and Nomenclature of Pachychoroid Disease
Section titled “Definition and Nomenclature of Pachychoroid Disease”The definition, diagnostic criteria, and nomenclature of the pachychoroid spectrum are not internationally unified, and there is inconsistency in terminology usage among research groups. 1) In a 2025 review, Cheung et al. emphasized the importance of clarifying the comprehensive definition of pachychoroid disease and deep phenotyping. 1)
Cheung et al. (2025) published a comprehensive review aimed at forming an international consensus on the definition, epidemiology, pathology, diagnosis, and treatment of pachychoroid disease as a whole. They argued that accurate classification of pachychoroid and non-pachychoroid conditions, enabled by advances in choroidal imaging technology, will be essential for future clinical trials. 1)
Choroid-Guided Treatment Strategy
Section titled “Choroid-Guided Treatment Strategy”The concept of “choroid-guided treatment,” which uses changes in choroidal thickness, blood flow, and pachyvessels as indicators of treatment efficacy, has been proposed. 1) There are also reports that the efficacy of anti-VEGF therapy differs between pachychoroid-type polypoidal choroidal vasculopathy and non-pachychoroid-type polypoidal choroidal vasculopathy, making treatment selection based on phenotype a future challenge. 2)
Next-generation anti-VEGF drugs
Section titled “Next-generation anti-VEGF drugs”Brolucizumab (anti-VEGF-A single-chain antibody) and faricimab (VEGF-A/Ang-2 bispecific antibody) are attracting attention as drugs that can extend the dosing interval for polypoidal choroidal vasculopathy and nAMD, and their application to pachychoroid disease is also being investigated. 2)
Through the accumulation of large-scale cohorts in international collaborative research and the detailed classification of pachychoroid phenotypes, it is expected that the natural course, risk factors for progression, and treatment response specific to pachydrusen will be elucidated. 1)
8. References
Section titled “8. References”-
Cheung CMG, Dansingani KK, Koizumi H, Lai TYY, Sivaprasad S, Boon CJF, Van Dijk EHC, Chhablani J, Lee WK, Freund KB.. Pachychoroid disease: review and update. Eye (Lond). 2025;39(5):819-834. doi:10.1038/s41433-024-03253-4. PMID:39095470; PMCID:PMC11933466.
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Sen P, Manayath G, Shroff D, Salloju V, Dhar P. Polypoidal Choroidal Vasculopathy: An Update on Diagnosis and Treatment. Clinical ophthalmology (Auckland, N.Z.). 2023;17:53-70. doi:10.2147/OPTH.S385827. PMID:36636621; PMCID:PMC9831529.
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日本網膜硝子体学会. 新生血管型加齢黄斑変性の診療ガイドライン（第2版）. 日本眼科学会雑誌. 2021.