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Updated: Feb 24, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Biomechanical stiffening: Slow low-irradiance corneal crosslinking versus the standard Dresden protocol
1From the Laboratory for Ocular Cell Biology (Kling, Hafezi), Center for Applied Biotechnology and Molecular Medicine, University of Zurich, and ELZA Institute AG (Hafezi), Zurich, and the Faculty of Medicine (Hafezi), University of Geneva, Geneva, Switzerland; Roski Eye Institute (Hafezi), University of Southern California, Los Angeles, California, USA.
Purpose:
To assess whether full biomechanical stiffening can be achieved with corneal crosslinking (CXL) when applying a reduced ultraviolet (UV) fluence during the standard irradiation time.
Setting:
Laboratory of Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.
Design:
Experimental study.
Methods:
Thirty-four freshly enucleated porcine corneas were deepithelialized and soaked with hypoosmolar riboflavin 0.1% solution for 30 minutes. Slow low-irradiance CXL (30 minutes at 1.5 mW/cm2, fluence 2.7 J/cm2) was compared with standard CXL (30 minutes at 3 mW/cm2, fluence 5.4 J/cm2). The controls were soaked with riboflavin but not exposed to UV light. Elastic (stress-strain) and viscoelastic (stress-relaxation) 2-dimensional testing was performed with a commercial stress-strain extensometer to quantify the biomechanical stiffening.
Results:
Corneas crosslinked with low and standard UV irradiances had a significantly higher mean elastic modulus (65.9 MPa ± 15.7 [SD] and 67.1 ± 15.6 MPa, respectively) than controls (52.4 ± 12.3 MPa) (P < .001). Also, the remaining stress after 120 seconds of stress-relaxation was significantly higher after CXL with low and standard UV irradiances (159 ± 21 kPa and 158 ± 25 kPa, respectively) compared with controls (135 ± 20 kPa) (P ≤ .013). No difference was observed in low and standard irradiances between CXL conditions (P = .64).
Conclusions:
The UV fluence for CXL might be reduced while maintaining the biomechanical efficacy by using a lower UV irradiance and the same irradiation duration. This might open avenues in the treatment of extremely thin corneas.
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