A research platform to investigate the aqueous humor outflow resistance at the level of distal vasculature

Abstract

Purpose : Glaucoma is a leading cause of global blindness. The intraocular pressure (IOP) outcomes of newer glaucoma surgeries are unpredictable, in part due to a gap in knowledge of tissue biomechanics at the level of distal aqueous humor (AH) outflow vasculature and perilimbal sclera (PLS). Investigating the outflow resistance within the distal vasculature requires isolation from that at the levels of the trabecular meshwork (TM) and inner wall of Schlemm Canal (SC). In addition, AH outflow vasculature is relatively acellular as these veins conduct the AH from the anterior chamber. Perfusion with contrast agent is necessary for measuring the morphology and the flow inside this vasculature. Finally, an imaging tool is needed to independently resolve the deformation of the distal vasculature and the surrounding perilimbal sclera at high contrast and resolution, and monitor the very slow flow rate in the vasculature.

Methods : We developed a clinically relevant model by trabeculotomy, leaving the outflow resistance only at the level of distal vasculature. In preliminary studies, porcine eyes were perfused with 3-µm-microsphere suspension at a constant flow rate of 3 µL/min for establishing a steady state IOP. Then, the flow rate was increased to 4.5 µl/min to elevate IOP to 22-28 mmHg. The morphology of the distal vasculature and the surrounding perilimbal sclera, as well as the flow velocity within the vasculature, were captured by a multispectral, optical resolution photoacoustic microscopy system.

Results : The results show that: 1) the cross-sectional area change of the distal vasculature is highly correlated with the deformation of PLS (R²=0.9, n=8); 2) eyes with larger cross-sectional area change have lower IOP (R²=0.9, n=8); 3) eyes with low strain in surrounding sclera (indicating high stiffness) have higher steady-state IOP (R²=0.6, n=8). The flow measurement ability of the system is validated by the fact that volume flow rate is constant through a closed system.

Conclusions : The results so far support our hypothesis that stiff PLS restricts the dilation of distal vasculature, and AH outflow resistance built up within the restricted distal vasculature, which leads to high IOP. We will further validate our hypothesis by measuring the volume flow rate through the distal vasculature by combining the flow velocity and the cross-sectional areas.

This abstract was presented at the 2024 ARVO Imaging in the Eye Conference, held in Seattle, WA, May 4, 2024.