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

Session Details

Session Title: Cross-linking

Session Date/Time: Monday 07/10/2013 | 14:30-16:30

Paper Time: 16:16

Venue: Elicium 2 (First Floor)

First Author: : J.Wernli SWITZERLAND

Co Author(s): :    S. Schumacher   E. Spoerl   M. Mrochen        

Abstract Details

Purpose:

Standard treatment in cases of progressive keratectasia is ultraviolet light-triggered corneal cross-linking (CXL) using riboflavin solution as a photosensitizer. A disadvantage of the current CXL standard protocol is the long illumination time of 30 minutes for the UV light which affects both the patient’s comfort and the doctor’s patient throughput. Therefore, a shorter CXL illumination time would be desirable. However, this leads to an increase of illumination intensity if the irradiation dose is kept constant. So far, for illumination intensities larger than 10 mW/cm2 and treatment times below 10 minutes, the scientific proof of a biomechanical strenghtening effect is insufficient. Thus, the aim of this work was to investigate the biomechanical strengthening of ex vivo corneal tissue with irradiances larger than 10mW/cm2.

Setting:

The study was carried out at the Department of Ophthalmology of the Carl Gustav Carus University Hospital Dresden in Dresden, Germany.

Methods:

To determine the efficacy of corneal cross-linking for higher intensities, the change in corneal stiffness that is evoked by the cross-linking treatment of ex vivo porcine corneal tissue was investigated. A total of 100 porcine eyes were randomly assigned into 10 treatment groups and received riboflavin + UV treatment (constant irradiation dose of 5.4 J/cm2) with different intensities varying from 3 to 90mW/cm2, and illumination times from 30 minutes to 1 minute, respectively. A control group of 80 eyes was not irradiated but underwent the same treatment otherwise. After CXL treatment a strip was cut out of each cornea along the superior-inferior axis, measuring 5 mm in width. Corneal stiffness of the strips was determined by uniaxial stress-strain measurement. Young’s modulus as a derivative of the stress-strain curve was determinded at 10% strain. Each treatment group was compared with the control group for statistical significance by means of a nonparametric Kruskal-Wallis test.

Results:

24 of 180 samples were excluded from data analysis due to procedural errors (e.g. slip of the probe in the probe holder). Box plots of Young’s moduli at 10% strain for the control and treatment groups were generated. Young’s modulus of the control group varied between 1300 kPa and 6550 kPa, with a median of 3350 kPa. Within the treatment groups, the median of the Young’s modulus varied between 3500 kPa and 7800 kPa. The performed Kruskal-Wallis test (Dunn criteria) showed a significant difference between groups (P < 0.0001). Post hoc analysis showed a statistically significant difference (? = 0.01) between the treatment groups from 3 mW/cm2 up to 45 mW/cm2 and the control group and no statistically significant difference between the treatment groups from 50 mW/cm2 up to 90 mW/cm2 and the control group. Evaluating the average increases in stiffness of all groups, one observes that the data follows a typical threshold function (Boltzmann function). The 50% limit is associated at approximately 47 mW/cm2 ± 1.5 mW/cm2.

Conclusions:

The collected data show the dependence of increase in corneal stiffness on illumination intensity while keeping a constant irradiation dose of 5.4 J/cm2. An equivalent stiffness increase can be achieved up to an illumination intensity of approximately 40 to 45 mW/cm2, corresponding to illumination times of approximately 2 minutes. For higher intensities ranging from 50 mW/cm2 up to 90 mW/cm2, no statistically significant stiffness increase could be achieved. The most interesting finding of this study is the failure of the Bunsen-Roscoe reciprocity law for short illumination time and high intensities. The Bunsen-Roscoe law describes the photoresponse of a material to a certain energy dose. The failure of the law observed in this study is probably due to the relative complex photochemistry that is not fully understood at this time. As a consequence, the corneal CXL-treatment with an irradiation dose of 5.4J/cm2 has an upper limit for the applied illumination intensity or lower limit for the illumination time, which seems to be at approximately 40 to 45 mW/cm2 and 2 minutes, respectively. In order to clarify the validity of these results for in vivo human corneal tissue, further experiments are necessary. Additionally, safety aspects at high intensities must be investigated. Other aspects that should be investigated in future studies are the influences of different concentrations of riboflavin and/or different irradiation energy doses. Potential effects of higher riboflavin concentrations could be higher protection of corneal endothelium and lens epithelium from UVA damage, and greater ability to allow tissue strengthening at irradiation intensities above 50 mW/cm2 and irradiation times of only 1 to 2 minutes.

Financial Interest:

... gains financially from product or procedure presented, ... travel has been funded, fully or partially, by a company producing, developing or supplying the product or procedure presented, ... research is funded, fully or partially, by a company producing, developing or supplying the product or procedure presented, ... receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented, ... has significant investment interest in a company producing, developing or supplying product or procedure presented