Perifoveal Exudative Vascular Anomalous Complex (PEVAC) is a solitary aneurysm-like vascular abnormality that occurs in the perifoveal capillary bed. It is associated with exudative changes and causes visual loss and metamorphopsia.
This is a relatively new disease concept first reported by Querques et al. in 2011, with few reported cases. The disease course is explained by a two-phase model: transition from phase 1 (non-exudative; nePVAC) to phase 2 (exudative; ePVAC) has been proposed 2, 3).
The age of onset is often middle-aged or older, with an average of around 70 years in reported cases. Bilateral cases have also been reported 1).
It is more common in middle-aged and older patients, especially those with a history of hypertension or stroke. In one report, about 70% of patients had hypertension and about 40% had a history of stroke 4).
The following findings are observed on slit-lamp microscopy and various imaging tests.
OCT Findings
Cystoid spaces with hyperreflective walls: Characteristic aneurysm-like structures with a dark lumen and hyperreflective walls 1, 2, 3, 4).
Surrounding retinal edema: Intraretinal edema with exudation is observed in the macula.
Thrombosis findings: Cases have been reported where the lumen becomes thrombosed and resolves during the disease course 2).
FA/ICGA Findings
Hyperfluorescence and leakage: Fluorescein angiography (FA) shows hyperfluorescence and leakage from the aneurysm-like structures 1).
Late staining: The walls of the aneurysm-like structures stain in the late phase.
No neovascularization: No evidence of choroidal neovascularization.
OCTA Findings
Abnormalities predominant in the deep capillary plexus (DCP): Optical coherence tomography angiography (OCTA) readily detects abnormal vascular structures in the deep capillary plexus 2, 4).
Visualization of vascular abnormalities: Aneurysmal dilations can be assessed noninvasively. Cases with a maximum diameter of up to 216 μm have been reported 4).
OCT can identify the morphology of aneurysm-like structures with hyperreflective walls and dark lumens, and OCTA can non-invasively evaluate abnormalities in the deep capillary layer 2, 4). Combining both can complement fluorescein angiography (FA) and other dye-based imaging to improve diagnostic accuracy.
The etiology of PEVAC remains largely unknown, but several hypotheses have been proposed.
Fundus examination with a slit-lamp microscope is fundamental, and diagnosis is made by combining OCT, FA, and OCTA. Suspect this disease when an isolated aneurysm-like structure is found in the deep capillary layer with exudation.
The roles of each examination are as follows:
Differentiating from similar diseases is an important step in diagnosis.
| Disease | Key Differences |
|---|---|
| Type 1 macular telangiectasia | Bilateral, diffuse dilation 4) |
| Type 3 MNV | Deep neovascularization, progressive |
| Macroaneurysm of capillary | Localized near the arterial trunk 4) |
There is no established standard treatment for PEVAC. The main treatment options at present are described below.
Anti-VEGF drugs are typically considered ineffective. There have been reports of cases that did not respond even after three doses of aflibercept 2). Although there is a case where complete resolution occurred after three doses of ranibizumab with no recurrence for five years 4), such successful cases are considered exceptional.
Savastano et al. (2025) reported a 57-year-old male who did not respond to three doses of aflibercept, but achieved complete remission (visual acuity 20/20) after full-threshold yellow laser (100mW/300ms/100μm) treatment 2). Thrombosis of the lesion was confirmed, and long-term remission was achieved.
Tombolini et al. (2022) reported a 74-year-old male whose lesion disappeared after treatment with diclofenac 0.1% eye drops twice daily for one month 3). The mechanism is thought to involve suppression of VEGF and angiopoietin 2 (Ang2) via COX-2 inhibition.
In some cases, spontaneous regression occurs without treatment. However, recurrence may also occur 1, 4).
Full-threshold laser photocoagulation is a viable option. Complete remission has been reported 2). Cases of regression with NSAIDs eye drops (diclofenac 0.1%) have also been reported 3), and treatment selection should be tailored to each individual case.
The pathophysiology of PEVAC is explained by two hypotheses: endothelial cell damage and pericyte loss.
Exudation in PEVAC is thought to have low VEGF dependence, leading to ineffectiveness of anti-VEGF drugs 2). A hypothesis has also been proposed that COX-2-mediated elevation of VEGF and Ang2 is involved in exudation 3), which is consistent with cases responding to NSAID eye drops.
According to Sacconil et al.’s two-phase model, the disease progresses as follows 2):
Spontaneous regression due to thrombosis is also explained within this model framework 2).
Savastano et al. (2025) reported achieving complete remission by directly irradiating aneurysmal-like structures with a full-threshold yellow laser (100mW/300ms/100μm) in cases where three doses of anti-VEGF drugs were ineffective 2). Histological evidence suggested thrombotic occlusion of the lesion, and visual acuity of 20/20 was maintained.
Tombolini et al. (2022) reported a case of PEVAC regression with 0.1% diclofenac eye drops, proposing a mechanism of COX-2 inhibition leading to decreased VEGF and Ang2 3). This is noted as an intervention targeting a different pathway from anti-VEGF therapy. They proposed the term PVAC (Perifoveal Vascular Anomalous Complex) as the disease concept.
A case has been reported where complete resolution occurred after three doses of ranibizumab, with no recurrence for five years 4). The existence of rare cases responsive to anti-VEGF drugs suggests heterogeneity in the pathology.
A case of bilateral PEVAC in a 56-year-old man with multiple myeloma has been reported 1). Along with reports of bilateral cases, an association with systemic diseases and the existence of bilateral onset are suggested. Meanwhile, recurrence three months after spontaneous regression was also documented 1).
Full-threshold laser has been effective in multiple cases, and future case accumulation and comparative studies are expected 2). Intervention in the COX-2 pathway with NSAIDs is also attracting attention as a new direction 3). Due to the rarity of the disease, building evidence through multicenter collaborative studies is a challenge.
