Mechanisms of macular oedema development and therapeutic response: An in-silico modelling study

Abstract

PurposeTo investigate the interplay between biomechanics, fluid dynamics, and solute transport in Diabetic Macular Oedema (DMO) using a mechanics-based computational model, aiming to elucidate mechanisms behind variable treatment outcomes. MethodsWe developed a multiphysics model of the retina within a porous media framework. The model integrates OCT-derived geometry, vascular leakage, retinal biomechanics (including Muller cell fibre architecture), retinal pigment epithelium (RPE) function, and anti-VEGF transport. We simulated oedema development and therapeutic response by varying these parameters systematically. ResultsModel results showed that active RPE pumping is essential for maintaining retinal dehydration. Our simulations revealed a critical trade-off related to Muller cell architecture: the physiological z-shaped orientation protects against oedema but impedes anti-VEGF drug delivery to leaky vessels. In contrast, a pathological, vertical Muller cell alignment increases oedema susceptibility but allows for a faster therapeutic response due to improved drug diffusion. ConclusionsMuller cell orientation presents a trade-off between biomechanical protection and therapeutic efficacy, offering a novel mechanistic explanation for the variable patient responses to anti-VEGF therapy observed clinically. This in-silico framework is a powerful tool for dissecting DMO pathophysiology and has the potential to guide the development of personalised treatment strategies.