Predicting retinal tissue oxygenation using an image-based theoretical model

Impaired oxygen delivery and tissue perfusion have been identified as significant factors that contribute to the loss of retinal ganglion cells in glaucoma patients. This study predicts retinal blood and tissue oxygenation using a theoretical model of the retinal vasculature based on confocal microscopy images of the mouse retina. These images reveal a complex and heterogeneous geometry of vessels that are distributed non-uniformly into multiple distinct retinal layers at varying depths. Predicting oxygen delivery and distribution in this irregular arrangement of retinal microvessels requires the use of an efficient theoretical model. The model employed in this work utilizes numerical methods based on a Green's function approach to simulate the spatial distribution of oxygen levels in a network of retinal blood vessels and the tissue surrounding them. Model simulations also predict the blood flow rates and pressures in each of the microvessels throughout the entire network. As expected, the model predicts that average vessel PO2 decreases as oxygen demand is increased. However, the standard deviation of PO2 in the vessels nearly doubles as oxygen demand is increased from 1 to 8 cm3 O2/100 cm3/min, indicating a very wide spread in the predicted PO2 levels, suggesting that average PO2 is not a sufficient indicator of oxygenation in a heterogeneous vascular network. Ultimately, the development of this mathematical model will help to elucidate the important factors associated with blood flow and metabolism that contribute to the vision loss characteristic of glaucoma

On the Indeterminates of Glaucoma:the Controversy of Arterial Blood Pressure and Retinal Perfusion

Glaucoma is a chronic eye disease characterized by thinning of the retina, death of ganglion cells, and progressive loss of vision, eventually leading to blindness. The prevalence of glaucoma is estimated at 1-3% of those over 40 years old. With a constantly aging population, this number is expected to increase significantly over the next 10 years. Even with treatment, about 15% of people with glaucoma currently develop residual vision or tunnel vision and eventually become blind or partially sighted. The mechanisms behind ganglion cell death are poorly understood. Elevated eye pressure is the main risk factor for glaucoma, but treatment in the form of medication, laser, or surgery can only slow the decline, not stop it. In addition, high intraocular pressure is neither necessary nor sufficient for the development of glaucoma, indicating the existence of other unknown risk factors. It has been established that the death of ganglion cells results in a decreased oxygen demand and a concomitant decrease in blood flow. However, there is also a hypothesis that reduced or unstable blood supply is not only a consequence, but also a cause of glaucoma. This is known as the ‘chicken-egg’ dilemma in glaucoma. It is supported by the observation that the risk of developing glaucoma is higher in people with very low blood pressure (sometimes even as a result of overtreatment of high blood pressure).This dissertation is an attempt to methodically examine whether blood pressure can be linked to changes in the retina that could suggest susceptibility to glaucoma. For this purpose, we analyze epidemiological data from the Groningen Longitudinal Glaucoma Study, we use advanced imaging techniques to model the microcirculation, and we describe its relationship with the neural structure and oxygen consumption of the retina. We provide evidence leaning towards the existence of a vascular component, likely pertinent to glaucoma