Pachychoroid neovasculopathy (PNV) is a disease concept named by Cheung et al. in 2015. It refers to a condition in which type 1 macular neovascularization (MNV) occurs under the retinal pigment epithelium (RPE) with a background of choroidal thickening (pachychoroid).
PNV is positioned as a disease progression (Stage III) of the pachychoroid spectrum disease (PSD). In the classification of MNV, it belongs to type 1 (sub-RPE) and is highly continuous with polypoidal choroidal vasculopathy. 5) Unlike age-related macular degeneration, it is characterized by the absence of drusen. PNV accounts for about half of nAMD in Japan, 7) and is estimated to correspond to about 25% of all age-related macular degeneration. 5)
Furthermore, it has been reported that 13.5% of PNV progresses to polypoidal choroidal vasculopathy, 5) and both are thought to form a continuous spectrum. Additionally, due to difficulty in differentiating from diseases with similar findings, misdiagnosis occurs in 14.3% of cases. 1)
PNV is sometimes classified as age-related macular degeneration, but it has a different background in that it does not involve drusen and choroidal thickening is central to the pathology. It accounts for about half of nAMD in Japan, 7) and is now treated as an independent disease concept.
In PNV, choroidal thickness is markedly increased, presenting characteristic OCT findings. The main findings are shown below.
OCT Findings
Choroidal thickening: SFCT (subfoveal choroidal thickness) is markedly thickened at 377±92 µm. 1)
Double layer sign: A double structure where neovascularization exists between the RPE and basement membrane. Present in 100% of PNV cases. 1)
SRF (subretinal fluid): Appears as serous retinal detachment. Present in 100% of PNV cases. 1)
Pigment epithelial detachment (RPE elevation): In PNV, the height is low and flat at 82±46 µm (significantly lower compared to PAT1: 1199±31 µm). 1)
Angiography Findings
SIRE (subretinal hyperreflective material): A characteristic finding observed in all PNV cases. 1)
Vortex vein anastomosis: Found in 95% of PNV, evidence of choroidal venous congestion. 6)
SHRM (subretinal hyperreflective material): In PNV, 28.6%, less frequent than PAT1 (71.4%). 1)
SRRLS (subretinal reverse reflection layer): 0% in PNV vs 71.4% in PAT1, useful for differentiation. 1)
The following shows the differences in key OCT findings between PNV and PAT1 (typical nAMD).
| Finding | PNV | PAT1 (typical nAMD) |
|---|---|---|
| PED height | 82±46 µm | 1199±31 µm |
| SRRLS | 0% | 71.4% |
| SHRM | 28.6% | 71.4% |
The double layer sign is an OCT finding where neovascular tissue is sandwiched between the RPE and Bruch’s membrane, appearing as a double-layer structure. It is observed in 100% of PNV cases and is an important indicator for diagnosis 1).
Structural and functional abnormalities of the choroid play a central role in the development of PNV.
OCT and OCTA play central roles in the diagnosis of PNV.
A cutoff value of 158 µm for peaking pigment epithelial detachment (high PED) on OCT has been reported, which is useful for differentiating from PAT1 type nAMD, showing high discriminative ability with an AUC of 0.969. 1) The presence or absence of SRRLS is also an important indicator for differentiation. 1)
For differentiating PNV from type 1 MNV associated with central serous chorioretinopathy, comprehensive evaluation of OCT and OCTA findings recommended by the Japanese guidelines for age-related macular degeneration is useful. 7)
The following table shows the key points for differentiating PNV from major diseases.
| Disease | Drusen | SFCT | PED Height |
|---|---|---|---|
| PNV | Absent | Thickened | Low (<158 µm) |
| Typical nAMD | Present | Normal to thin | High (≥158 µm) |
| Central serous chorioretinopathy | None | Thickened | Low to moderate |
Anti-VEGF drugs are the first-line treatment. 7)PNV tends to require fewer anti-VEGF injections compared to age-related macular degeneration. 5)The drugs used are as follows.
PDT alone or in combination with anti-VEGF drugs is effective. 5)Half-dose PDT (HF-PDT) can maintain efficacy while reducing effects on the choroid.
Yamada et al. (2022) reported that a 89-year-old patient treated with half-dose PDT (HF-PDT) combined with intravitreal aflibercept showed complete resolution of serous retinal detachment (SRD) after 3 months. 4)This report also documented the world’s first case of vortex vein occlusion after HF-PDT.
Anti-VEGF alone
First-line: Recommended by the Japanese Clinical Practice Guideline for Age-Related Macular Degeneration. 7)
Fewer injections: Tends to be fewer than for age-related macular degeneration. 5)
Management of recurrence: PRN or Treat-and-Extend regimen is used.
PDT Combination
Spironolactone
Indications: Considered as adjunctive therapy for anti-VEGF non-responders.
Mechanism: As a mineralocorticoid receptor antagonist, it suppresses choroidal fluid accumulation. 2)
Reported cases: At 25 mg BID, SRF decreased by 51% at 6 weeks and 90% at 12 weeks. CT decreased from 366 to 214 µm (42% reduction). 2)
For cases unresponsive to anti-VEGF monotherapy, combination with PDT is an effective option. 5) There are also case reports of marked efficacy with spironolactone. 2) For details, see the “Standard Treatment” section. Consultation with the attending physician is important.
The pathology of PNV is based on structural and hemodynamic abnormalities of the choroid.
A common pathology in pachychoroid spectrum diseases (PSD) is stasis of the vortex veins. Vortex vein anastomosis is observed in 95% of PNV, 98% of polypoidal choroidal vasculopathy, and 90% of central serous chorioretinopathy (normal SFCT 267.5 µm). 6)
When vortex vein stasis occurs, MNV develops through the following pathway:
Central serous chorioretinopathy → PPE (pachychoroid pigment epitheliopathy) → PNV → polypoidal choroidal vasculopathy are thought to form a continuous spectrum. 5) This concept of a disease continuum well explains the progression from PNV to polypoidal choroidal vasculopathy (13.5%). 5)
Sen et al. (2023) reported that the frequency of vortex vein anastomosis in PNV is high: 95% in PNV, 98% in polypoidal choroidal vasculopathy, and 90% in central serous chorioretinopathy, with marked choroidal thickening compared to normal eyes (SFCT 267.5 µm). 6) These findings support the mechanism by which dilation of Haller layer vessels compresses the Sattler layer, leading to ischemia and MNV formation.
In MNV evaluation using OCTA, a sensitivity of 97% has been reported, greatly exceeding that of conventional ICGA (sensitivity 66%), 5) improving the diagnostic accuracy of PNV. With the introduction of a new concept called SIRE (a composite index of sub-retinal pigment epithelium hyperreflective material), the differentiation between PNV, polypoidal choroidal vasculopathy, and typical age-related macular degeneration is becoming more precise. 5)
MRAs (mineralocorticoid receptor antagonists), typified by spironolactone, are thought to exert their effects by blocking pathways involved in choroidal fluid regulation.
Keidel LF et al. (2021) reported a case of PNV refractory to 29 anti-VEGF injections, in which spironolactone 25 mg BID was administered, resulting in a 51% reduction in SRF at 6 weeks, 90% reduction at 12 weeks, and a marked decrease in choroidal thickness from 366 to 214 µm (42% reduction). 2)
Validation through large-scale randomized trials remains a future challenge.
Long-term outcomes of novel agents targeting multiple VEGF isoforms and angiopoietin (e.g., faricimab), as well as the potential of gene therapy, are under investigation. Interventions targeting the choroidal venous system (e.g., PDT for vortex veins) are also being explored. 6)
