PEVAC

– PEVAC is a rare, unilateral, typically unifocal, perifoveal aneurysmal lesion first described in 2011 by Querques et al., characterized by a single, massive aneurysm with intraretinal cystic edema, exudation, and hemorrhages.

– Nonexudative PEVAC (nePVAC) is the precursor, progressing to exudative PEVAC (ePVAC) in ~75% of cases within 15 ± 9 months, with visual impairment (e.g., metamorphopsia, reduced best-corrected visual acuity [BCVA]).

– Mean baseline BCVA is 20/50 (range 20/200–20/20), with a male predominance (60% male vs. 40% female).

– Pathophysiology is unclear but likely involves progressive retinal endothelial cell degeneration and reduced pericyte coverage due to increased matrix metalloproteinase-9 (MMP-9) expression, leading to aneurysm formation per Laplace’s law (increased wall tension, reduced wall strength).

– PEVAC occurs in healthy eyes but is associated with age-related macular degeneration (AMD) (34%), myopia (7%), pachychoroid (2%), lamellar hole with epiretinal proliferation (1%), and vitreoretinal adhesion (2%).

– Rare cases reported with diabetes, multiple myeloma, and pachychoroid pigment epitheliopathy, though these may be classified as PEVAC-like lesions with distinct etiologies.

– PEVAC presents as a grey lesion on fundus exam with small retinal hemorrhages (23%), lipid exudates (30%), intraretinal cysts (71.5%), and subretinal fluid (7%), typically within 405 μm of the fovea.

– Lesion size averages 161 × 147 μm; mean central macular thickness (CMT) in ePVAC is 288 ± 66 μm.

– Multifocal PEVAC occurs in 9% of cases; bilateral involvement is rare (1 case reported).

– Optical Coherence Tomography (OCT):

  – Lesions are located between the outer plexiform layer (OPL) and ganglion cell complex (GCL), commonly between the inner nuclear layer (INL) and OPL.

  – Shows a round/oval hyperreflective wall surrounding a dark lumen, often with intraretinal cysts and rare subretinal fluid, without retinal pigment epithelium (RPE) involvement.

  – Enface OCT may reveal a “hematocrit sign” due to slow flow within the lesion.

– OCT Angiography (OCTA):

  – Detects flow in the superficial capillary plexus (SCP) (12%), deep capillary plexus (DCP) (40%), both SCP+DCP (43%), or DCP+avascular slab (5%), with perilesional capillary rarefaction and vascular loops.

  – No choriocapillaris flow or retinal-choroidal anastomosis; a shadow effect is constant in choriocapillaris segmentation.

  – Suspended Scattered Particles in Motion (SSPiM) may indicate precursor exudates.

– Fluorescein Angiography (FA): Shows well-defined hyperfluorescence with variable late leakage.

– Indocyanine Green Angiography (ICGA): Hyperfluorescent lesion without leakage.

– Key differentials include retinal angiomatous proliferation (RAP), retinal arterial macroaneurysms (RAM), macular telangiectasia (MacTel), and diabetic microaneurysms:

  – RAP: Type 3 neovascularization involving RPE/sub-RPE, responds to anti-VEGF, no lumen on OCT, and shows retinal-choroidal anastomosis on ICGA.

  – RAM: Solitary, larger aneurysms outside the fovea, often with multilayer hemorrhages, typically at arterial bifurcations.

  – MacTel Type 1: Multiple telangiectasias/microaneurysms in younger patients, temporal macula, unlike PEVAC’s isolated perifoveal lesion in older patients.

  – Diabetic microaneurysms: Smaller, associated with retinopathy, not isolated like PEVAC.

– PEVAC-like lesions share features but are linked to underlying vasculopathy (e.g., diabetes, AMD) and may be multifocal or bilateral.

– Deep Retinal Age-Related Microvascular Anomalies (DRAMA): Smaller or multiple capillary dilatations, potentially part of the PEVAC spectrum.

– nePVAC is asymptomatic; ePVAC develops exudation, reducing BCVA (e.g., 20/25 to 20/40) and increasing CMT (268 to 339 μm).

– Stable course without significant spontaneous improvement; 33% of cases may show spontaneous resolution of intraretinal cysts.

– No standardized treatment exists due to variable responses:

  – Anti-VEGF (aflibercept, ranibizumab, bevacizumab): Generally ineffective, with rare successes (e.g., aflibercept resolving lesions in some cases, possibly via placental growth factor inhibition).

  – Laser therapy: Effective in multiple reports:

    – Thermal laser: Resolves exudation (e.g., 50–100 mW, 50–100 μm, 50–100 ms), but risks retinal scarring, scotoma, or choroidal neovascularization.

    – Subthreshold micropulse laser (MPL): Noninvasive, effective (e.g., 577 nm, 160 μm, 300 mW), with improved BCVA and no recurrence in some cases.

  – Steroids (e.g., triamcinolone): Variable success, with resolution in some anti-VEGF-unresponsive cases.

  – Observation: Viable for nePVAC or stable ePVAC, but progression risk warrants monitoring.

  – Topical NSAIDs: Emerging option for exudation resolution.

– Proposed approach: Start with anti-VEGF or MPL; reserve thermal laser for non-foveal lesions or failures, with close nePVAC follow-up.

– Need for randomized trials to compare anti-VEGF vs. laser efficacy.

– Identification of prognostic biomarkers for treatment response.

– Standardized protocols (e.g., loading phase vs. single injection) and evaluation of new anti-VEGF agents.

– Clarification of PEVAC vs. PEVAC-like lesions and their relation to DRAMA.

Citation Address of the Uploaded Paper

Carlà, M. M., Boselli, F., Giannuzzi, F., Crincoli, E., Cusato, M., Peschiaroli, S., & Rizzo, S. (2025). A comprehensive review on the perifoveal exudative vascular anomalous complex. *Retina*, 45(4), 587–600. https://doi.org/10.1097/IAE.0000000000004078

Notes for Board Review

– Memorize imaging hallmarks: OCT (hyperreflective wall, lumen, cysts), OCTA (SCP/DCP flow, capillary rarefaction), and FA/ICGA findings.

– Understand treatment challenges: anti-VEGF’s limited efficacy vs. laser’s success, with MPL as a safer option.

– Be prepared for questions on distinguishing PEVAC from mimics and recognizing its stable but vision-threatening course.

– Future directions are less likely to be tested but reflect evolving management trends.

In Optical Coherence Tomography Angiography (OCTA) images, SSPiM refers to Suspended Scattering Particles in Motion, which is a non-vascular decorrelation signal that can be observed. 

Here’s a breakdown:

1. What are Suspended Scattering Particles in Motion (SSPiM)?

Appearance on OCTA: SSPiM appear as distinct, localized areas with a flow-like signal, especially on en face OCTA images. 

Corresponding OCT: These areas correspond to hyperreflective intraretinal fluid on the structural OCT B-scan. 

Location: They tend to occur at the vascular-avascular junction, for instance, at the edge of the foveal avascular zone or along the borders of retinal vessels. 

Interpretation: The OCTA signal in SSPiM is believed to be due to the movement (e.g., Brownian motion) of particles within this intraretinal fluid, which is rich in proteins and lipids, caused by the breakdown of the blood-retinal barrier.

2. Significance of SSPiM in OCTA:

Indicator of Blood-Retinal Barrier Breakdown: SSPiM can be a sign of increased permeability of retinal vessels, indicating fluid leakage and potential exudation. 

Associated with Exudative Maculopathies: SSPiM is seen in various retinal vascular diseases, particularly those with exudative features, like diabetic retinopathy, retinal vein occlusions, and neovascular age-related macular degeneration. 

Potential Biomarker: SSPiM is being explored as a potential biomarker for assessing disease activity and treatment response. 

Impact on Treatment Response: Some studies suggest the presence of SSPiM is associated with poorer response to certain treatments, like anti-VEGF injections for macular edema. 

3. How is SSPiM identified and distinguished from other OCTA signals?

Careful examination: Look for areas of flow-like signal on OCTA, especially in non-vascular locations, near the FAZ or vessel borders. 

Corresponding structural OCT: Check for hyperreflective intraretinal fluid corresponding to the flow signal on OCTA. 

Distinguish from artifacts: Projection artifacts can mimic flow in deeper layers, but careful examination of the OCT B-scan helps in identifying SSPiM. 

Distinguish from projection artifacts: Projection artifacts typically align vertically with superficial vessels, whereas SSPiM corresponds to hyperreflective fluid at the vascular-avascular junction.