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Corneal Cross-Linking in Keratoconus

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Abstract

Corneal cross-linking (CXL) was first introduced into clinical practice over 20 years ago for the treatment of corneal ectasia, keratoconus. CXL was defined by the “Dresden protocol” which specified that keratoconic corneas ≥400 μm in thickness could be saturated in 0.1% riboflavin (after epithelial cell debridement), then irradiated with 365–370 nm ultraviolet (UV)-A energy at an intensity of 3 mW/cm2 UV-A irradiation for 30 min to deliver a total UV-A fluence of 5.4 J/cm2. This chapter documents the insight into the CXL photochemical reactions, the discovery that oxygen is an essential component of the CXL reaction, and the progress that has been made in not only developing accelerated, higher-intensity CXL-for-ectasia treatments, but also epithelium-on CXL, using approaches like iontophoresis delivery of riboflavin to the corneal stroma through an intact epithelium, the use of penetration enhancers, pulsed UV irradiation, and supplemental oxygen. A side benefit of the UV-riboflavin photochemical reaction is that the production of reactive oxygen species (ROS), not only cross-links the molecules of the corneal stroma together, but through steric hindrance, also reduces the metalloproteinase-binding sites available, protecting the stroma from enzymatic digestion. The ROS also bind and lyse pathogen cell membranes and intercalate with pathogen nucleic acids, inhibiting their reproduction. Practically, this means that a cross-linked cornea is rendered sterile at the end of the procedure, and this antibiotic-free pathogen-killing effect has not gone unnoticed.

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Authors and Affiliations

  1. Ocular Cell Biology Group, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

    Farhad Hafezi

  2. ELZA Institute AG, Dietikon, Switzerland

    Farhad Hafezi & Mark Hillen

  3. Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Farhad Hafezi

  4. Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Farhad Hafezi

  5. Department of Ophthalmology, Wenzhou Medical University, Wenzhou, China

    Farhad Hafezi

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  1. Farhad Hafezi
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  2. Mark Hillen
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Correspondence to Farhad Hafezi .

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Editors and Affiliations

  1. L V Prasad Eye Institute, Bhubaneswar, Odisha, India

    Sujata Das

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Hafezi, F., Hillen, M. (2022). Corneal Cross-Linking in Keratoconus. In: Das, S. (eds) Keratoconus. Springer, Singapore. https://doi.org/10.1007/978-981-19-4262-4_14

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  • DOI: https://doi.org/10.1007/978-981-19-4262-4_14

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