MMP-9-responsive contact lens facilitating disease-adaptive and safer dexamethasone delivery for corneal neovascularization therapy.

Corneal neovascularization (CNV), an inflammation-driven pathological process responsible for irreversible vision loss, remains an urgent unmet challenge in ophthalmic medicine. Current interventions-ranging from surgery to topical steroids-fail to prevent recurrence or avoid severe side effects like intraocular hypertension and even corneal ulceration. Here, we introduce CL-Peptide-Dex, a transformative contact lens (CL) engineered for matrix metalloproteinase-9 (MMP-9)-responsive dexamethasone (Dex) release, to resolve this decades-long challenge. By grafting dexamethasone onto the lens surface via an MMP-9-cleavable peptide linker (GPLGLAGC), CL-Peptide-Dex achieves disease-adaptive drug delivery: rapid release during acute inflammation and sustained release throughout CNV progression. Unlike conventional drug-eluting systems, this surface-grafting strategy eliminates burst release while preserving lens transparency and oxygen permeability. In the rabbit corneal neovascularization model, a single administration of CL-Peptide-Dex could maintained a stable Dex level for 7 d, suppressed VEGF by 77.5%, and reduced neovascular area by 79.5%. Critically, CL-Peptide-Dex avoided intraocular pressure spikes and exhibited good corneal biocompatibility and compliance, enabling safe extended wear. By integrating MMP-9-responsive precision delivery with a patient-friendly design, CL-Peptide-Dex represents a significant advance in precision ophthalmology.