Corneal neovascularization (CNV) remains a significant clinical challenge for ophthalmologists, often leading to inflammation, scarring, and vision loss in patients. Although anti-vascular endothelial growth factor (VEGF) therapies have transformed the management of ocular neovascular disease, their delivery typically requires invasive intraocular injections – an approach associated with patient discomfort, procedural risk, and reduced compliance. Now, a new study proposes a potential alternative: non-invasive antibody eye drops capable of penetrating ocular barriers and suppressing pathologic angiogenesis.
In research published in Nano Research, the China-based investigators developed a novel topical therapy based on a small anti-VEGF antibody combined with a penetration-enhancing nanoformulation. The team first identified a single-domain antibody, termed sdVE01, designed to target VEGF. Compared with the widely used anti-VEGF drug ranibizumab, sdVE01 is roughly three times smaller while maintaining comparable anti-angiogenic activity to the therapeutic antibody’s functional heavy-chain region. This reduced size was intended to improve tissue penetration – one of the major barriers to effective topical biologic therapies.
To further enhance delivery, the researchers engineered a series of dithiolane molecule (DM)–based nanoformulations. These molecules form reversible interactions with biological surfaces, helping transport the antibody across ocular barriers. The resulting DM-antibody complexes were designed as topical eye drops capable of reaching deeper ocular tissues.
Laboratory studies confirmed that the nanoformulated antibody retained strong VEGF-binding and anti-angiogenic properties. In cellular assays, the treatment inhibited endothelial cell proliferation, migration, and tube formation – key processes in pathological neovascularization. The investigators then evaluated the approach in animal models of corneal neovascularization.
Topical administration of the DM-antibody eye drops in a corneal alkali-burn rat model were found to significantly suppress corneal neovascular growth compared with untreated controls, achieving effects comparable to that of ranibizumab, without any observed toxicity. Importantly, the nanoformulation enabled efficient posterior penetration into ocular tissues, despite the protective barriers of the cornea and tear film.
The study authors suggest that combining a smaller antibody format with a penetration-enhancing nanocarrier may overcome long-standing obstacles in delivering biologics to the eye through topical routes. If confirmed in further studies, this strategy could offer a non-invasive alternative to intraocular injections for certain ocular neovascular conditions, reducing reliance on injections and improving patient adherence.
The authors note that further studies – including evaluation in larger animal animals such as non-human primates – will now be needed to confirm long-term safety, pharmacokinetics, biocompatibility, and efficacy in human subjects. Nonetheless, the work provides an intriguing proof-of-concept that biologic therapies – traditionally delivered by injection – may one day be administered as simple topical eye drops.
