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Updated: Jun 9, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
[Light-induced immunomodulation : Corneal cross-linking to reduce neovascularization and optimize outcomes prior to
Johanna Wiedemann1, Mert Mestanoglu2, Simona Schlereth2,3
1Zentrum für Augenheilkunde, Medizinische Fakultät und Universitätsklinikum Köln, Universität zu Köln, Kerpenerstr. 62, 50937, Köln, NRW, Deutschland. johanna.wiedemann@uk-koeln.de.
Background:
Corneal cross-linking (CXL) is a minimally invasive procedure originally developed to stabilize progressive keratoconus. It is now used in various corneal diseases. In addition to its well-known biomechanical stiffening effect, CXL also demonstrates anti-inflammatory and immunomodulatory properties as well as the ability to induce regression of corneal neovascularization.
Objective:
To summarize and evaluate the biomechanical, antiangiogenic and immunomodulatory effects of CXL and to assess its potential to improve outcomes in high-risk keratoplasty.
Material And Methods:
The Dresden protocol serves as the foundation of the procedure, using riboflavin-mediated UVA photochemistry to induce cross-linking of stromal collagen. Variations include accelerated, epithelium-on and high fluence protocols, for example in the treatment of corneal neovascularization.
Results:
Clinical and preclinical data demonstrate long-term stabilization of the cornea in keratoconus, often reducing the need for transplantation. Additionally, peripheral CXL leads to a significant reduction in corneal neovascularization, decreased infiltration of inflammatory cells and downregulation of proangiogenic and lymphangiogenic markers. Experimental studies suggest that performing CXL prior to high-risk keratoplasty can reduce the risk of immunological graft rejection.
Conclusion:
The use of CXL has evolved from a purely biomechanical treatment into a versatile approach with antiangiogenic and immunomodulatory properties. While initial results are promising, optimal indications, dosages and combination treatment remain the subject of ongoing research.
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