The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time.

PURPOSE: Standard treatment in cases of progressive keratectasia is UV-triggered corneal cross-linking. For irradiances larger than 10 mW/cm(2) and treatment times below 10 minutes, the scientific proof of a biomechanical strengthening effect is insufficient. The authors investigated the biomechanical strengthening of ex vivo corneal tissue treated with irradiances between 3 mW/cm(2) and 90 mW/cm(2) and illumination times from 30 minutes to 1 minute, respectively. METHODS: A total of 100 porcine eyes received riboflavin + UV treatment (constant irradiation dose of 5.4 J/cm(2)) with different intensities and illumination times and were randomly assigned into 10 groups. A control group (80 eyes) was not irradiated but underwent the same treatment otherwise. Young's modulus at 10% strain was determined for each strip after uniaxial stress-strain measurement. A Kruskal-Wallis test was used for statistical analysis. RESULTS: A statistically significant difference (α = 0.01) was found between the median value of Young's modulus of the treatment groups up to 45 mW/cm(2) (illumination times from 30 minutes to 2 minutes) compared with the control group. There was no statistically significant difference between the treatment groups from 50 mW/cm(2) up to 90 mW/cm(2) (illumination times of less than 2 minutes) and the control group. CONCLUSIONS: The ex vivo results of corneal cross-linking performed in porcine corneas show that the Bunsen-Roscoe reciprocity law is only valid for illumination intensities up to 40 to 50 mW/cm(2) and illumination times of more than 2 minutes. Further experiments are necessary to validate these results for in vivo human corneal tissue. Additionally, safety aspects at high intensities must be investigated.

Initial surface temperature of PMMA plates used for daily laser calibration affects the predictability of corneal refractive surgery.

PURPOSE: To investigate the relevance of initial temperature of the polymethylmethacrylate (PMMA) plates used as a target for photoablation during calibration of excimer lasers performed in daily clinical routine. METHODS: An experimental argon fluoride excimer laser with a repetition rate of 1050 Hz, a radiant exposure of 500 mJ/cm², and single pulse energy of 2.1 mJ was used for photoablation of PMMA plates. The initial plate temperature varied from 10.1°C to 75.7°C. The initial temperature was measured with an infrared camera and the central ablation depth of a myopic ablation of -9.00 diopters (D) with an optical zone of 6.5 mm was measured by means of a surface profiling system. RESULTS: The ablation depth increased linearly from 73.9 to 96.3 µm within a temperature increase from 10.1°C to 75.7°C (increase rate of 0.3192 µm/K). The linear correlation was found to be significant (P<.05) with a coefficient of determination of R²=0.95. Based on these results and assuming a standard room temperature of 20°C, optimal plate temperature was calculated to be 15°C to 25°C to maintain an ablation within 0.25 D. CONCLUSIONS: The temperature of PMMA plates for clinical laser calibration should be controlled ideally within a range of approximately ±5°C, to avoid visually significant refractive error due to calibration error. Further experimental investigations are required to determine the influence of different initial corneal temperatures on the refractive outcome.

Optimization model for UV-riboflavin corneal cross-linking.

PURPOSE: To develop a theoretical model for riboflavin ultraviolet-A cross-linking treatment that can predict the increase in stiffness of the corneal tissue as a function of the ultraviolet intensity and riboflavin concentration distribution, as well as the treatment time. METHODS: A theoretical model for calculating the increase in corneal cross-linking (polymerization rate) was derived using Fick's second law of diffusion, Lambert-Beer's law of light absorption, and a photopolymerization rate equation. Stress-strain experiments to determine Young's modulus at 5% strain were performed on 43 sets of paired porcine corneal strips at different intensities (3-7 mW/cm²) and different riboflavin concentrations (0.0%-0.5%). The experimental results for Young's modulus increase were correlated with the simulated polymerization increase to determine a relationship between the model and the experimental data. RESULTS: This model allows the calculation of the one-dimensional spatial and temporal intensity and concentration distribution. The total absorbed radiant exposure, defined by intensity, concentration distribution, and treatment time, shows a linear correlation with the measured stiffness increase from which a threshold value of 1.7 J/cm² can be determined. The relative stiffness increase shows a linear correlation with the theoretical polymer increase per depth of tissue, as calculated by the model. CONCLUSIONS: This theoretical model predicts the spatial distribution of increased stiffness by corneal cross-linking and, as such, can be used to customize treatment, according to the patient's corneal thickness and medical indication.

Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear.

We investigated the hypothesis that exogenous collagen cross-linking can augment intact regions of tendon to mitigate mechanical propagation of partial tears. We first screened the low toxicity collagen cross-linkers genipin, methylglyoxal and ultra-violet (UV) light for their ability to augment tendon stiffness and failure load in rat tail tendon fascicles (RTTF). We then investigated cross-linking effects in load bearing equine superficial digital flexor tendons (SDFT). Data indicated that all three cross-linking agents augmented RTTF mechanical properties but reduced native viscoelasticity. In contrast to effects observed in fascicles, methylglyoxal treatment of SDFT detrimentally affected tendon mechanical integrity, and in the case of UV did not alter tendon mechanics. As in the RTTF experiments, genipin cross-linking of SDFT resulted in increased stiffness, higher failure loads and reduced viscoelasticity. Based on this result we assessed the efficacy of genipin in arresting tendon tear propagation in cyclic loading to failure. Genipin cross-linking secondary to a mid-substance biopsy-punch significantly reduced tissue strains, increased elastic modulus and increased resistance to fatigue failure. We conclude that genipin cross-linking of injured tendons holds potential for arresting tendon tear progression, and that implications of the treatment on matrix remodeling in living tendons should now be investigated.