A nanotechnology‐based solution for epi‐on corneal cross‐linking

Abstract

Keratoconus (KC) is a bilateral progressive corneal ectasia resulting in irregular astigmatism and loss of visual function, in youth and children. Corneal cross‐linking (CXL) is the standard treatment to halt the progression of KC. The conventional protocol consists of removal of the corneal epithelium (epi‐off), followed by soaking of riboflavin and then irradiation with UVA light, leading to stiffening of the cornea. However, postoperative ocular adverse events related to epithelial removal, such as infectious keratitis and delayed visual recovery, have been described. Some alternative methodologies have been tested but pain, no control on corneal permeability, and high investment for set‐up acquisition are drawbacks. Accordingly, the treatment of KC is at an extremely exciting stage, and research on delivering riboflavin into the cornea without removing the epithelium is underway.To address this clinical unmet need, we developed an advanced solution consisting of nanoparticle‐modified commercial soft contact lenses. Safety conditions were determined using ex vivo porcine eyes. The efficacy of our solution on corneal epithelial permeability to riboflavin was tested using in vivo rat eyes. Our nanotechnology‐based solution allows high spatial and temporal precision control of epithelial permeability to riboflavin. We aim to validate this innovative strategy as an epithelium‐on (epi‐on) protocol for the effective treatment of KC, with obvious advantages in terms of safety, patient comfort, and recovery time. Furthermore, our strategy is compatible with current equipment and riboflavin solutions, allowing to capitalize clinicians' expertise and the resources already existing in private clinics and public health services.This project was financially supported by Foundation for Science and Technology (FCT, Portugal): Exploratory Research Project EXPL/BIA‐BQM/0042/2021, Strategic Projects UIDB/04539/2020, UIDP/04539/2020, and UID/NEU/04539/2019; and by COMPETE‐FEDER (POCI‐01‐0145‐FEDER‐007440).