Targeting Corneal Neovascularization: Development of Innovative Treatment using Topical anti-VEGF Peptidomimetics – STOP-NEO

Pathological neovascularization (NV) of the cornea is a serious condition that poses a significant risk of rapid and irreversible visual loss. It is involved in chemical burns, infectious keratitis, inflammatory diseases, and corneal transplantation rejection. Corneal NV is finely regulated by angiogenic factors, in particular the vascular endothelial growth factor (VEGF).
Current treatments have largely been limited to off-label anti-VEGF injections into the corneal stroma or subconjunctival space, which pose significant challenges. Topical administration of existing anti-VEGF drugs, with limited corneal penetration, is only effective at doses that risk damaging the corneal epithelium. Developing a high-affinity, topical anti-angiogenic agent that inhibits pathological NV without invasive procedures or adverse effects on corneal nerves and epithelium would be a major breakthrough in ophthalmology—a true game changer—and remains a significant global challenge in therapeutic ophthalmology.
The objective of this project is to advance the optimization of our novel anti-VEGF peptide therapeutics for treating corneal pathological NV by topical application in preclinical animal models. We aim to enhance the peptides’ corneal penetration, minimize toxicity in both in vitro and in vivo models, and maximize anti-neovascularization efficacy. The project is an integrative approach with interdisciplinary research combining biophysics, chemistry, cytology, and biology of the eye. The teams of the consortium are specialized in medicinal chemistry (anti-VEGF peptides), intermolecular associations and in vitro cell effects (Université Paris Cité, Faculty of Pharmacy), and preclinical models of corneal NV and inflammation (Vision Institute).
This work will lay the foundation for more effective, safer treatments for corneal NV, with strong potential for future clinical applications.