History of Corneal Cross-Linking

Farhad Hafezi; Sabine Kling; Nikki L Hafezi; M Enes Aydemir; Nan-Ji Lu; Mark Hillen; Boris Knyazer; Shady Awwad; Cosimo Mazzotta; Léonard Kollros; Emilio A Torres-Netto

doi:10.1016/j.preteyeres.2024.101322

History of Corneal Cross-Linking

Prog Retin Eye Res. 2024 Dec 14:101322. doi: 10.1016/j.preteyeres.2024.101322. Online ahead of print.

Authors

Affiliations

¹ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Laboratory for Ocular Cell Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland; Department of Ophthalmology, University of Wenzhou, Ouhai District, Wenzhou, 325015, China; Department of Ophthalmology, NYU Grossman School of Medicine, 550 1st Avenue, New York, NY 10016, United States; National Eye Institute of Uzbekistan, Shakhrisabz 40, Tashkent, Uzbekistan.
² Institute for Biomedical Engineering, ITET Department, ETH Zurich, Gloriastrasse 35, CH-8092, Zurich, Switzerland; ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
³ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Laboratory for Ocular Cell Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; National Eye Institute of Uzbekistan, Shakhrisabz 40, Tashkent, Uzbekistan; Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
⁴ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Laboratory for Ocular Cell Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
⁵ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Laboratory for Ocular Cell Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium; Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China.
⁶ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland.
⁷ Ophthalmology Department, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Yitzhack I. Rager Boulevard 151, Be'er Sheva, Israel.
⁸ Department of Ophthalmology, American University of Beirut Medical Center, Riad El Solh, Beirut, Lebanon.
⁹ Siena Cross-Linking Center, Siena, Italy.
¹⁰ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Fachhochschule Nordwestschweiz FHNW, Institute for Optometry, Riggenbachstrasse 16, CH-4600, Olten, Switzerland.
¹¹ ELZA Institute, Webereistrasse 2, CH-8953 Dietikon, Switzerland; Laboratory for Ocular Cell Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland.

PMID: 39681212
DOI: 10.1016/j.preteyeres.2024.101322

Abstract

Corneal cross-linking (CXL) has profoundly changed the management of keratoconus and other ectatic corneal diseases. Introduced in the late 1990s, CXL marked the first effective intervention to halt disease progression. This chapter describes the history of CXL, beginning with its conceptual foundations and preclinical studies conducted at the University of Dresden. Early experiments established the efficacy of riboflavin and UV-A light to induce collagen cross-linking, which improved corneal stiffness. Clinical translation followed with the Dresden protocol, demonstrating safety and efficacy. Long-term studies confirm sustained benefits, with advances in accelerated protocols and modifications for thin corneas extending eligibility to more patients. Additionally, CXL has expanded into infectious keratitis treatment and refractive surgery. Emerging innovations, such as customized and two-photon CXL, promise further applications. By examining the milestones in its evolution, this paper highlights the transformative impact of CXL on corneal disease management.

Keywords: Corneal cross-linking; PACK-CXL; cornea; endothelium; epithelium; keratitis.

Publication types

Review