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 evade 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 on 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 maintain a stable Dex level for 7 days, 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 patient-friendly design, CL-Peptide-Dex represents a significant advance in precision ophthalmology.