# Reduced ocular perfusion after intravitreal Aflibercept and faricimab: an exploratory study for Tie2 receptor distribution in ophthalmic capillaries

## TL;DR

This study explores how two drugs, Aflibercept and Faricimab, affect blood flow in the eye of patients with a specific type of macular degeneration.

## Contribution

The study reveals that Faricimab causes a faster reduction in retinal blood flow compared to Aflibercept, suggesting differences in Tie2 receptor distribution.

## Key findings

- Faricimab caused a significant and rapid decrease in retinal vessel perfusion within one week.
- Both drugs significantly reduced choroidal perfusion after one and four weeks.
- The different vascular responses suggest variations in Tie2 receptor distribution.

## Abstract

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections reduce ocular perfusion in patients with neovascular age-related macular degeneration (nAMD). Faricimab blocks both, VEGF-A and Angiopoietin-2. The study investigated the effects of intravitreal Aflibercept or Faricimab on ocular perfusion in patients with nAMD.

36 eyes of 36 Caucasian patients with nAMD were initially enrolled and treated with either Aflibercept (n = 18) or Faricimab (n = 18). Two patients were excluded after screening failures, resulting in 34 eyes (n = 17 per group) for analysis. Ocular perfusion was assessed using Laser Speckle Flowgraphy (LSFG) at baseline, and 1 and 4 weeks after the first injection. The main output parameter of LSFG, mean blur rate (MBR), was measured in the optic nerve head (ONH) and macula. MBR, defined by an ellipsoid region of interest (ROI), was calculated for the total ONH area (ONH-MA), major retinal vessels within the ONH (ONH-MV), and the tissue area containing microvasculature (ONH-MT). For macular measurements, a square ROI (150 × 150 pixels) was placed temporal to the optic disc to measure choriocapillaris perfusion (CHOR) without including main retinal vessels.

Faricimab group showed a significant decrease in MV (p = 0.006) after one week, while the decrease with Aflibercept was not significant after one week (p = 0.29). After 4 weeks, both groups showed a significant decrease (p = 0.003 and p = 0.017, respectively). For MT and CHOR, both groups showed a significant decrease in perfusion, both after one and after 4 weeks (p < 0.001).

Faricimab caused a more rapid decrease in retinal perfusion, while choroidal perfusion was equally reduced by Aflibercept and Faricimab. These different responses in the vascular systems seem to indicate a different distribution of Tie2 receptors for Angiopoietin-2. These findings warrant further investigation into the role of Tie2 receptors in the vascular response to anti-VEGF therapies.