A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data

Abstract

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.

The ocular mathematical virtual simulator: A validated multiscale model for hemodynamics and biomechanics in the human eye

“…Alternatively, a porous media model could have been used to describe blood flow dynamics in this tissue, similarly to the lamina cribrosa. However, the internal retinal vasculature is more complex than the lamina cribrosa and it is not fully understood yet 101 . Moreover, the images that can be obtained on the retina are mostly reduced to a small portion of the total tissue, usually the fundus, which is the part close to the optic nerve head.…”

“…However, the internal retinal vasculature is more complex than the lamina cribrosa and it is not fully understood yet. 101 Moreover, the images that can be obtained on the retina are mostly reduced to a small portion of the total tissue, usually the fundus, which is the part close to the optic nerve head. Second, the present configuration of the OMVS does not incorporate the effect of the vitreous humor and only accounts for a steady description of the aqueous humor, in which the IOP value is considered constant.…”

Advancing treatment of retinal disease through in silico trials

“…Compartmental models have been used to investigate the relationships between intravascular and extravascular pressures and haemodynamics in the retina and choroid [64,93,120,205,226,233,254,256]. In these models, similar vessels are sorted into compartments, e.g.…”

“…Conversely, in the in series configuration, blood inflow comes solely from the SVP, while venous drainage occurs only in the DCP. We refer the reader to figure 1 in the paper by Chiaravalli et al for a schematic of these two configurations [64]. The compartmental models developed in this paper simulate haemodynamics between the CRA and the CRV in five vascular compartments [64].…”

“…We refer the reader to figure 1 in the paper by Chiaravalli et al for a schematic of these two configurations [64]. The compartmental models developed in this paper simulate haemodynamics between the CRA and the CRV in five vascular compartments [64]. The authors modelled both configurations and compared the responses of each plexus to IOP elevation and occlusion of the CRV.…”