Ronald R Krueger1, Satish Herekar, Eberhard Spoerl. 1. Department of Ophthalmology (R.R.K.), Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cole Eye Institute, Cleveland Clinic, Cleveland, OH; Department of Science and Technology (S.H.), Avedro Inc., Menlo Park, CA; and Department of Natural Sciences (E.S.), Carl Gustav Carus Technical University of Dresden, Dresden, Germany.
Abstract
PURPOSE: To document the first presented report in December 2008 of high irradiance riboflavin/ultraviolet A (UVA) corneal cross-linking in comparison with that of standard irradiance and of fractionated exposure to increase the time for oxygen diffusion into the cornea. METHODS: After in vitro studies of oxygen depletion and cross-linking density using type 1 human collagen gels, 36 ex vivo porcine globes were deepithelialized and exposed to 0.1% riboflavin drops in carboxymethylcellulose solution every 5 min for 3 initial doses and then throughout irradiation afterward. Six eyes each were irradiated with 370-nm UVA light at 2, 3, 9, and 15 mW/cm continuously and 15 mW/cm fractionated (with alternate cycles of 30 s "ON" and 30 s "OFF" exposure) using an equivalent radiant exposure of 5.4 mJ/cm. The final six eyes received no UVA exposure as a control. The exposed corneas were then dissected and subjected to extensiometry. Analysis of variance with Bonferroni post hoc test was performed between groups. RESULTS: The stress required to induce a 10% strain for the control eyes (no UVA) was 100.6±20.9×10 N/m in comparison with the stress of 3 mW/cm (standard irradiation) at 146.7±17.6×10 N/m (P=0.009). The stress at the other equidose irradiances of 2, 9, 15 continuously, and 15 mW/cm fractionated were 140±21.9, 162.8±70, 154.1±70, and 163.0±64×10 N/m, respectively. When comparing the irradiances of 15 mW/cm continuously and fractionated to the standard irradiation, the stress was not statistically different (P=0.799 and 0.643), respectively. CONCLUSION: High irradiance riboflavin/UVA cross-linking with equivalent energy exposure demonstrates comparable efficacy in stiffening corneal collagen with standard irradiance, but with considerably less exposure time. Over the past 6 years, since this report was first presented, the use of high irradiance cross-linking has been gaining popularity.
PURPOSE: To document the first presented report in December 2008 of high irradiance riboflavin/ultraviolet A (UVA) corneal cross-linking in comparison with that of standard irradiance and of fractionated exposure to increase the time for oxygen diffusion into the cornea. METHODS: After in vitro studies of oxygen depletion and cross-linking density using type 1 human collagen gels, 36 ex vivo porcine globes were deepithelialized and exposed to 0.1% riboflavin drops in carboxymethylcellulose solution every 5 min for 3 initial doses and then throughout irradiation afterward. Six eyes each were irradiated with 370-nm UVA light at 2, 3, 9, and 15 mW/cm continuously and 15 mW/cm fractionated (with alternate cycles of 30 s "ON" and 30 s "OFF" exposure) using an equivalent radiant exposure of 5.4 mJ/cm. The final six eyes received no UVA exposure as a control. The exposed corneas were then dissected and subjected to extensiometry. Analysis of variance with Bonferroni post hoc test was performed between groups. RESULTS: The stress required to induce a 10% strain for the control eyes (no UVA) was 100.6±20.9×10 N/m in comparison with the stress of 3 mW/cm (standard irradiation) at 146.7±17.6×10 N/m (P=0.009). The stress at the other equidose irradiances of 2, 9, 15 continuously, and 15 mW/cm fractionated were 140±21.9, 162.8±70, 154.1±70, and 163.0±64×10 N/m, respectively. When comparing the irradiances of 15 mW/cm continuously and fractionated to the standard irradiation, the stress was not statistically different (P=0.799 and 0.643), respectively. CONCLUSION: High irradiance riboflavin/UVA cross-linking with equivalent energy exposure demonstrates comparable efficacy in stiffening corneal collagen with standard irradiance, but with considerably less exposure time. Over the past 6 years, since this report was first presented, the use of high irradiance cross-linking has been gaining popularity.
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