Comparative CFD modelling of the interplay between aqueous humour hydrodynamics and drug and nanocarrier transport for glaucoma drug delivery via intracameral injection, drug-eluting implants and contact lenses

Glaucoma is the leading cause of irreversible blindness worldwide and often requires long-term administration of intraocular pressure-lowering agents. The effectiveness of ocular drug delivery depends not only on the delivery route, but also on the transport mechanisms governing drug distribution within the eye. In this study, a computational fluid dynamics (CFD) framework was developed to investigate the interplay between aqueous humour hydrodynamics and the transport of both dissolved drug and nanocarriers delivered through three mechanisms, including intracameral injection, drug-eluting implants and contact-lens administration. An idealised three-dimensional model of the anterior segment was implemented in COMSOL Multiphysics v6.4, incorporating aqueous humour flow, thermal convective effects, drug transport, saccadic movements and particle tracing. This approach enabled comparison between molecular diffusion-dominated and particle-mediated delivery. The simulations revealed substantial differences in intraocular transport behaviour among the delivery strategies. Contact-lens delivery produced the most spatially homogeneous distributions, whereas implant-based delivery generated persistent concentration gradients associated with localised release. Intracameral injection exhibited intermediate behaviour, with rapid redistribution of the administered agent by aqueous humour circulation. Nanocarrier transport exhibited greater spatial heterogeneity within the anterior chamber than dissolved-drug transport owing to the reduced particle diffusivity and the resulting advection-dominated transport. The results demonstrate that aqueous humour hydrodynamics constitute an independent determinant of ocular drug transport. Accounting for these physiological effects may therefore improve the design and optimisation of sustained ophthalmic drug delivery systems. The proposed modelling framework will provide a useful tool for the design and optimisation of diluted-drug and nanocarrier-based glaucoma drug delivery systems in the future.