Computational modelling of scleral photocrosslinking: from rat to minipig to human.

Abstract

Selective scleral crosslinking has been proposed as a novel treatment to increase scleral stiffness to counteract biomechanical changes associated with glaucoma and high myopia. Scleral stiffening has been shown by transpupillary peripapillary scleral photocrosslinking in rats, where the photosensitizer, methylene blue (MB), was injected retrobulbarly and red light initiated crosslinking reactions with collagen. Here, we adapted a computational model previously developed to model this treatment in rat eyes to additionally model MB photocrosslinking in minipigs and humans. Increased tissue length and subsequent diffusion and light penetration limitations were found to be barriers to achieving the same extent of crosslinking as in rats. Per cent inspired O₂, injected MB concentration and laser fluence were simultaneously varied to overcome these limitations and used to determine optimal combinations of treatment parameters in rats, minipigs and humans. Increasing these three treatment parameters simultaneously resulted in maximum crosslinking, except in rats, where the highest MB concentrations decreased crosslinking. Additionally, the kinetics and diffusion of photocrosslinking reaction intermediates and unproductive side products were modelled across space and time. The model provides a mechanistic understanding of MB photocrosslinking in scleral tissue and a basis for adapting and screening treatment parameters in larger animal models and, eventually, human eyes.