Influence of UVA-Riboflavin corneal collagen cross-linking on biomechanical properties of keratoconic eyes

1. Influence of UVA-Riboflavin corneal collagen cross-linking on biomechanical properties of keratoconic eyes David Zadok MD, Yakov Goldich MD, Yaniv Barkana MD, Adi Rasko MD, Isaac Avni MD Department of Ophthalmology Assaf Harofeh Medical Center Israel The authors have no conflicts of interest and no financial interest in the article’s subject matter or methods mentioned.

2. Background • Corneal Collagen-Cross linking (CXL) using UVA and Riboflavin was proposed recently as treatment to stop progression of keratoconus1 • A suggested mechanism is stiffening of the cornea2 1.Wollensak G. et al, Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. 2.Kohlhaas M. et al, Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006 Feb;32(2):279-83.

3. Background • The Ocular Response Analyzer (ORA; Reichert Inc) provides in vivo measurements of corneal biomechanical properties, namely corneal hysteresis (CH) and corneal resistance factor (CRF), and non contact measurements of IOP: Goldmann correlated IOP (IOPg) and corneal compensated IOP (IOPcc)

4. Purpose • To assess changes in biomechanical properties of human corneas following treatment of keratoconus with UVA-Riboflavin CXL

5. Methods • Ten eyes of 10 patients aged 26.5±5.7 years were treated with CXL and assessed with the ORA • Inclusion criteria • progressive keratoconus documented clinically ( Astigmatic refraction and/or topography) within the past 12 months • Age >18 years • Absence of corneal opacities • No previous ocular surgeries • Minimum corneal thickness > 400 μm • No wearing of rigid contact lenses for 1 month before initial evaluation

6. Methods • Treatment: corneal deepithelization, instillation of 0.1% riboflavin in 20% dextran solution every 5 minutes for 40 minutes and corneal irradiation with UVA 3 mW/cm2 for 30 minutes • Patients were assessed before, 1week, 1month and 3 months after treatment. Comparison of postoperative to preoperative measurements was done

7. Results • CH and CRF were transiently elevated after cross-linking treatment, without statistical significance. • IOPcc and IOPg were statistically significantly higher at 1 week and 1 month. • The results presented in table and box and whisker plots (smallest, median and largest values with interquartile range) showing values before treatment (Preop) and on 1 week, 1 month and 3 months thereafter.

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11. Discussion • Previous in vitro studies showed increased corneal rigidity after CXL treatment using biomechanical stress-strain measurements3 • In this study there were no significant changes in biomechanical properties of human corneas as measured in vivo by ORA following CXL treatment. CH and CRF were transiently elevated 1 week after treatment, but without statistical significance • IOPcc and IOPg were statistically significantly higher at 1 week and 1 month • ORA-measured IOP changes may be a measurement artifact following changes in ocular characteristics (like increased corneal thickness), and not a real IOP elevation . 3.Wollensak G. et al, Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg. 2003 Sep;29(9):1780-5.

12. Conclusions There were no differences in corneal biomechanical properties as measured with the Ocular Response Analyzer following corneal collagen cross-linking in keratoconus Correspondence: David Zadok MDemail: dzadok@yahoo.com