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Safety of UVA-Riboflavin Cross-Linking of the Cornea

Spoerl, Eberhard PhD*; Mrochen, Michael PhD; Sliney, David PhD; Trokel, Stephen MD§; Seiler, Theo MD, PhD

doi: 10.1097/ICO.0b013e3180334f78

Purpose: To study potential damage to ocular tissue during corneal collagen cross-linking (X-linking) by means of the riboflavin/UVA (370 nm) approach.

Methods: Comparison of the currently used technique with officially accepted guidelines regarding direct UV damage and the damage created by the induced free radicals (photochemical damage).

Results: The currently used UVA radiant exposure of 5.4 mJ/cm2 and the corresponding irradiance of 3 mW/cm2 is below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damage caused by the free radicals, the damage thresholds for keratocytes and endothelial cells are 0.45 and 0.35 mW/cm2, respectively. In a 400-μm-thick cornea saturated with riboflavin, the irradiance at the endothelial level was 0.18 mW/cm2, which is a factor of 2 smaller than the damage threshold.

Conclusions: After corneal X-linking, the stroma is depopulated of keratocytes ∼300 μm deep. Repopulation of this area takes up to 6 months. As long as the cornea treated has a minimum thickness of 400 μm (as recommended), the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina. The light source should provide a homogenous irradiance, avoiding hot spots.

From the *Department of Ophthalmology, Universitätsklinikum Dresden, Dresden, Germany; the †IROC-Institut für Refraktive und Ophthalmochirurgie, Zurich, Switzerland; the ‡Laser/Optical Radiation Program, US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD; and the §Edward S. Harkness Eye Institute, New York, NY.

Received for publication April 27, 2006; revision received October 22, 2006; accepted December 25, 2006.

Dr. Mrochen has a financial interest in UVA riboflavin cross-linking.

Reprints: Theo Seiler, IROC, Stockerstr 37, CH-8002 Zurich, Switzerland (e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.