Customized Corneal Cross‐Linking With Microneedle‐Mediated Riboflavin Delivery For Keratoconus Treatment

To develop a customized corneal cross-linking (CXL) strategy using microneedle-mediated riboflavin delivery to enhance stromal penetration while preserving the corneal epithelium, thereby improving the safety and efficacy of keratoconus treatment.

Academic ophthalmic research center, Eye & ENT Hospital of Fudan University, Shanghai, China.

A microneedle-based delivery system was designed to facilitate localized riboflavin penetration into the corneal stroma without epithelial removal. Controlled microchannels were created on the corneal surface to allow efficient diffusion of riboflavin. Following drug delivery, ultraviolet-A (UVA) irradiation was applied to induce collagen cross-linking within the corneal stroma. Riboflavin distribution, stromal penetration depth, and cross-linking efficiency were evaluated using fluorescence imaging and biomechanical testing. Corneal transparency, epithelial integrity, and stromal architecture were assessed by slit-lamp examination and histological analysis.

Microneedle-mediated delivery significantly improved riboflavin penetration into the corneal stroma compared with conventional topical administration. The approach enabled uniform riboflavin distribution while maintaining epithelial integrity. Subsequent UVA irradiation effectively induced stromal cross-linking, resulting in enhanced corneal biomechanical strength. No significant corneal haze or structural damage was observed, and epithelial recovery remained rapid. The customized approach demonstrated improved drug delivery efficiency and favorable safety profiles.

Microneedle-assisted riboflavin delivery provides a promising strategy for customized corneal cross-linking. By enhancing stromal drug penetration while preserving the corneal epithelium, this approach may offer a safer and more efficient alternative to conventional epithelium-off CXL for keratoconus treatment.