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Alice Chandra Verticchio Vercellin, Alon Harris, Nicholas Marazzi, Louis R Pasquale, Brent A Siesky, Ingrida Januleviciene, Giovanna Guidoboni; Intraocular pressure and retinal blood flow regulation: a mathematical model to understand the role of the retinal veins. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1738.
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© ARVO (1962-2015); The Authors (2016-present)
In this study, we define and quantify novel biomarkers of retinal vasculature including the venous compartment (retinal venules and central retinal vein, CRV) and the regulation of retinal blood flow in response to intra-ocular pressure (IOP) changes utilizing mathmatical model simulations.
The retinal vasculature is modeled as a network of 5 compartments: the central retinal artery (CRA), arterioles, capillaries, venules, and the CRV (Fig 1). Vascular resistances (R) in the CRA (R1c, R1d), venules (R4a, R4b) and CRV (R5a, R5b) are assumed to vary passively with transmural pressure. Active regulation of retinal arterioles is not included. The total retinal blood flow (Q) is driven by Pin (blood pressure, BP, upstream of the CRA, ranging between 58 and 70 mmHg) and Pout (BP downstream of the CRV, kept equal to 14 mmHg), with Pin=2/3*(2/3*DP+1/3DP), where SP and DP are systolic and diastolic blood pressures. IOP elevation induces changes in the transmural pressure and, consequently, the vascular resistances. The model was used to predict how Q and R respond to IOP elevation (between 10 and 50 mmHg).
The model predicts a major shift in retinal hemodynamic response when IOP is around 20 mmHg, with a minimal influence of Pin, as shown in Fig 2. Following IOP increases from 10 mmHg to 20 mmHg, Q remains almost constant thanks to an increase in venular resistances (R4a, R4b) that induces a local increase in pressure gradient. When IOP is higher than 20 mmHg, the CRV, rather than the venules, bears the majority of the external load. An increase in CRV resistance (R5a, R5b) helps establish a larger pressure gradient and prevent the collapse of retinal venules, which will ultimately occur at different IOP values depending on the systemic blood pressure Pin.
Our mathematical model suggests a critical role of the retinal venules in the regulation of the blood flow in response to IOP changes. The retinal venous compartment may be an important target for future estimation of risk and treatment target development in the management of glaucoma.
This is a 2020 ARVO Annual Meeting abstract.
FIGURE 1. Network model for the retinal vasculature
FIGURE 2. Vascular resistances (R) (top) and total retinal blood flow (Q) as a function of intraocular pressure (IOP).
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