Speaker
Description
Wet age-related macular degeneration is a chronic ocular disease treated by repeated intravitreal injections. The relatively short intravitreal half-life of these therapeutics leads to frequent administration, creating a substantial treatment burden. Accurate estimation of the effective diffusion coefficient is central to predicting intravitreal half-life and to the rational design of longer-lasting treatments.
Quantitative investigation of intraocular drug transport is challenging: experimental access to the eye is limited, and the vitreous humour is a structurally complex, heterogeneous medium. Classical approaches estimate diffusion coefficients in substitute materials or extracted samples, which do not faithfully represent the intact vitreous. Recently, collaborators developed a method to measure diffusion in intact ex vivo vitreous. We analyse these data for molecules of varying sizes using a profile likelihood framework to estimate effective diffusion coefficients, assess practical identifiability, derive confidence intervals, and investigate the influence of molecular size and charge on transport. Comparison with synthetic data evaluates parameter recoverability under the experimental protocol. Our analysis shows partial practical identifiability, with confidence intervals dominated by measurement uncertainty and potential bias for highly charged molecules, indicating the need for experimental refinement and improved modelling of charge-dependent transport.
