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Arthur Hammer, Olivier Richoz, David Tabibian, Florence Hoogewoud, Farhad Hafezi; Corneal biomechanical properties in corneal collagen cross-linking (CXL) at high fluences. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4073.
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© ARVO (1962-2015); The Authors (2016-present)
The current intensity/irradiation profile for collagen cross-linking (3 mW/cm2 for 30 minutes) has been in clinical use since 1999 in a multitude of studies. Lately, different irradiation profiles have emerged, with the intention to lower irradiation time while maintaining the total energy dose (Bunsen-Roscoe law). Little is known whether these modified irradiation profiles will lead to the same increase in biomechanical stiffness observed in the original protocol.
We investigated the biomechanical properties in ex vivo porcine corneas at 3 (n = 10), 9 (n = 10), and 18 (N = 12) mW/cm2 for various time periods (30, 10, 5 minutes), while maintaining the total energy dose identical (Bunsen-Roscoe law). Prior to irradiation, riboflavin 0.1% was applied on the de-epithelialized cornea for 20 minutes. Controls (n = 11) were treated similarly, but without UV-A irradiation. Stress-strain measurements were performed using an extensometer (Zwick Roell, Model ZO.05, Zwick GmbH & Co. KG, Ulm, Germany).
We observed a decrease in Young’s modulus with increasing UV-A intensity (fluence). Young’s modulus at 4 %, 6 %, 8 % and 10 % strain at 3 mW/cm2 was 1.66 N, 0.75 N, 0.44 N and 0.29 N respectively. At 9 mW/cm2, we measured 1.52 N, 0.7 N, 0.39 N and 0.24 N, whereas at 18 mW/cm2, we detected 1.2 N, 0.57 N, 0.33 N and 0.21 N for 18 mW. Controls showed 0.72 N, 0.37 N, 0.37 N and 0.16 N.
The increase in biomechanical strength of the porcine cornea following CXL diminishes with increasing fluence/decreasing irradiation time, even if the total energy dose is maintained. The generation of chemical bonds during cross-linking is an oxygen-dependent process that depends on intra-stromal oxygen concentration. Oxygen diffusion capacity is limited within the stroma and the increased oxygen consumption at higher fluence/lower irradiation time might become a limiting factor for cross-linking, leading to the observed decrease in treatment efficacy.
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