Customized Corneal Cross‐Linking with Microneedle‐Mediated Riboflavin Delivery for Keratoconus Treatment

Author:

Yang Mei1,Pan Hongxian1,Chen Tingting2,Chen Xin1,Ning Rui1,Ye Qianfang2,Chen Aodong2,Li Jiawei2,Li Siheng1,Zhao Nan1,Wu Yue1,Fu Xueyu1,Meek Keith M.3,Chen Lingxin1,Wang Xiaoying1,Chen Zhongxing1,Zhou Xingtao1,Huang Jinhai1ORCID

Affiliation:

1. Eye Institute and Department of Ophthalmology Eye & ENT Hospital NHC Key laboratory of Myopia and Related Eye Diseases Key Laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences Shanghai Research Center of Ophthalmology and Optometry Fudan University Shanghai 200030 China

2. School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical University Wenzhou Zhejiang 325027 China

3. School of Optometry and Vision Sciences Cardiff Institute for Tissue Engineering and Repair School of Pharmacy and Pharmaceutical Sciences Cardiff University Redwood Building, King Edward VII Avenue Cardiff CF10 3NB UK

Abstract

AbstractIn this study, a novel customized corneal cross‐linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional “one‐size‐fits‐all” approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi‐circular, annular and butterfly shaped, are crafted for loading an optimized RF‐hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross‐linking effects that are comparable to the conventional epi‐off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.

Funder

Medical Research Council

Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning

National Natural Science Foundation of China

Publisher

Wiley

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