In vitro and ex vivo models of microbial keratitis: Present and future.

Microbial keratitis (MK) is an infection of the cornea, caused by bacteria, fungi, parasites, or viruses. MK leads to significant morbidity, being the fifth leading cause of blindness worldwide. There is an urgent requirement to better understand pathogenesis in order to develop novel diagnostic and therapeutic approaches to improve patient outcomes. Many in vitro, ex vivo and in vivo MK models have been developed and implemented to meet this aim. Here, we present current in vitro and ex vivo MK model systems, examining their varied design, outputs, reporting standards, and strengths and limitations. Major limitations include their relative simplicity and the perceived inability to study the immune response in these MK models, an aspect widely accepted to play a significant role in MK pathogenesis. Consequently, there remains a dependence on in vivo models to study this aspect of MK. However, looking to the future, we draw from the broader field of corneal disease modelling, which utilises, for example, three-dimensional co-culture models and dynamic environments observed in bioreactors and organ-on-a-chip scenarios. These remain unexplored in MK research, but incorporation of these approaches will offer further advances in the field of MK corneal modelling, in particular with the focus of incorporation of immune components which we anticipate will better recapitulate pathogenesis and yield novel findings, therefore contributing to the enhancement of MK outcomes.