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Computational modelling of ocular pharmacokinetics
Pharmacokinetics in the eye is an important factor for the success of ocular drug delivery and treatment. Pharmacokinetic features determine the feasible routes of drug administration, dosing levels and intervals, and it has impact on eventual drug responses. Several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during treatment during local (topical, subconjunctival, intravitreal) and systemic administration (intravenous, per oral). Mathematical models integrate joint impact of various barriers on ocular pharmacokinetics (PKs) thereby helping drug development. The models are useful in describing (top-down) and predicting (bottom-up) pharmacokinetics of ocular drugs. This is useful also in the design and development of new drug molecules and drug delivery systems. Furthermore, the models can be used for interspecies translation and probing of disease effects on pharmacokinetics. In this lecture, ocular pharmacokinetics and current modelling methods (noncompartmental analyses, compartmental, physiologically based, and finite element models) are introduced. Future challenges are also highlighted (e.g. intra-tissue distribution, prediction of drug responses, active transport).
Why age-related macular degeneration is a mathematically tractable disease
Among all prevalent diseases with a central neurodegeneration, AMD can be considered the most promising in terms of prevention and early intervention, due to several factors surrounding the neural geometry of the foveal singularity. • Steep gradients of cell density, deployed in a radially symmetric fashion, can be modeled with a difference of Gaussian curves. • These steep gradients give rise to huge, spatially aligned biologic effects, summarized as the Center of Cone Resilience, Surround of Rod Vulnerability. • Widely used clinical imaging technology provides cellular and subcellular level information. • Data are now available at all timelines: clinical, lifespan, evolutionary • Snapshots are available from tissues (histology, analytic chemistry, gene expression) • A viable biogenesis model exists for drusen, the largest population-level intraocular risk factor for progression. • The biogenesis model shares molecular commonality with atherosclerotic cardiovascular disease, for which there has been decades of public health success. • Animal and cell model systems are emerging to test these ideas.
Foundation models in ophthalmology
Abstract to follow.
Computational and mathematical approaches to myopigenesis
Myopia is predicted to affect 50% of all people worldwide by 2050, and is a risk factor for significant, potentially blinding ocular pathologies, such as retinal detachment and glaucoma. Thus, there is significant motivation to better understand the process of myopigenesis and to develop effective anti-myopigenic treatments. In nearly all cases of human myopia, scleral remodeling is an obligate step in the axial elongation that characterizes the condition. Here I will describe the development of a biomechanical assay based on transient unconfined compression of scleral samples. By treating the scleral as a poroelastic material, one can determine scleral biomechanical properties from extremely small samples, such as obtained from the mouse eye. These properties provide proxy measures of scleral remodeling, and have allowed us to identify all-trans retinoic acid (atRA) as a myopigenic stimulus in mice. I will also describe nascent collaborative work on modeling the transport of atRA in the eye.
Diverse applications of artificial intelligence and mathematical approaches in ophthalmology
Ophthalmology is ideally placed to benefit from recent advances in artificial intelligence. It is a highly image-based specialty and provides unique access to the microvascular circulation and the central nervous system. This talk will demonstrate diverse applications of machine learning and deep learning techniques in ophthalmology, including in age-related macular degeneration (AMD), the leading cause of blindness in industrialized countries, and cataract, the leading cause of blindness worldwide. This will include deep learning approaches to automated diagnosis, quantitative severity classification, and prognostic prediction of disease progression, both from images alone and accompanied by demographic and genetic information. The approaches discussed will include deep feature extraction, label transfer, and multi-modal, multi-task training. Cluster analysis, an unsupervised machine learning approach to data classification, will be demonstrated by its application to geographic atrophy in AMD, including exploration of genotype-phenotype relationships. Finally, mediation analysis will be discussed, with the aim of dissecting complex relationships between AMD disease features, genotype, and progression.
Deep learning applications in ophthalmology
Deep learning techniques have revolutionized the field of image analysis and played a disruptive role in the ability to quickly and efficiently train image analysis models that perform as well as human beings. This talk will cover the beginnings of the application of deep learning in the field of ophthalmology and vision science, and cover a variety of applications of using deep learning as a method for scientific discovery and latent associations.
Unique features of oxygen delivery to the mammalian retina
Like all neural tissue, the retina has a high metabolic demand, and requires a constant supply of oxygen. Second and third order neurons are supplied by the retinal circulation, whose characteristics are similar to brain circulation. However, the photoreceptor region, which occupies half of the retinal thickness, is avascular, and relies on diffusion of oxygen from the choroidal circulation, whose properties are very different, as well as the retinal circulation. By fitting diffusion models to oxygen measurements made with oxygen microelectrodes, it is possible to understand the relative roles of the two circulations under normal conditions of light and darkness, and what happens if the retina is detached or the retinal circulation is occluded. Most of this work has been done in vivo in rat, cat, and monkey, but recent work in the isolated mouse retina will also be discussed.
retina coverage
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