Preclinical Models of Rare Corneal and Ocular Surface Diseases: a Comprehensive Narrative Review.

Rare eye diseases of the cornea and ocular surface (REDs) remain a clinical challenge owing to their low prevalence, heterogeneous presentation, and limited therapeutic options. As REDs mechanisms are often complex, preclinical models are essential to advance mechanistic understanding and support the development of targeted treatments. This review provides a comprehensive overview of the experimental platforms currently available to study REDs, including in vitro models such as primary and engineered cell systems, coculture approaches, and emerging 3D organoid technologies. In addition, we summarize in vivo strategies ranging from surgically induced models to genetic and transgenic systems that reproduce the relevant ocular phenotypes. By comparing the strengths, limitations, and translational value of these complementary approaches, this review offers an integrated perspective on how preclinical modeling can be optimized to investigate REDs pathophysiology. Furthermore, we highlight how emerging tools-such as organ-on-chip platforms and artificial intelligence-assisted analytics-may enhance model fidelity and accelerate the identification of effective therapeutic strategies.