Advancing treatment of retinal disease through in silico trials

Treating retinal diseases to prevent sight loss is an increasingly important challenge. Thanks to the configuration of the eye, the retina can be examined relatively easily in situ. Owing to recent technological development in scanning devices, much progress has been made in understanding the structure of the retina and characterising retinal biomarkers. However, treatment options remain limited and are often of low efficiency and efficacy. In recent years, the concept of in silico clinical trials (ISCTs) has been adopted by many pharmaceutical companies to optimise and accelerate the development of therapeutics. ISCTs rely on the use of mathematical models based on the physical and biochemical mechanisms underpinning a biological system. With appropriate simplifications and assumptions, one can generate computer simulations of various treatment regimens, new therapeutic molecules, delivery strategies and so forth, rapidly and at a fraction of the cost required for the equivalent experiments. Such simulations have the potential not only to hasten the development of therapies and strategies but also to optimise the use of existing therapeutics. In this paper, we review the state-of-the-art in in silico models of the retina for mathematicians, biomedical scientists and clinicians, highlighting the challenges to developing ISCTs. Throughout this paper, we highlight key findings from in silico models about the physiology of the retina in health and disease. We describe the main building blocks of ISCTs and identify challenges to developing ISCTs of retinal diseases.