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Cornea. 2018 Oct;37(10):1218-1225. doi: 10.1097/ICO.0000000000001707.

Corneal Cross-Linking: Current USA Status: Report From the Cornea Society.

Author information

Department of Ophthalmology & Vision Science, University of Arizona, Tucson, AZ.
Singapore National Eye Center, Singapore.
Avedro Inc, Waltham, MA.
See Clearly Vision Group, Mclean, Virginia.
ELZA Institute, Zurich, Switzerland.
Department of Ophthalmology and Visual Sciences, Federal University of Sao Paulo, Sao Paulo, Brazil.
Department of Ophthalmology, University of Brest, Brest, France.


The initial published clinical report on riboflavin/ultraviolet A corneal cross-linking (CXL) for treatment of progressive keratoconus dates back to 2003. CXL has since then been widely used outside the United States for treatment of progressive keratoconus and post-laser in situ keratomileusis ectasia. The Food and Drug Administration (FDA) approved Avedro Inc.'s corneal cross-linking system (KXL) for treatment of patients with progressive keratoconus and post-laser in situ keratomileusis ectasia in April 2016. The procedure is not currently approved for stable keratoconus. There are 2 FDA-approved topical ophthalmic solutions for use in CXL. Riboflavin 5'-phosphate in 20% dextran ophthalmic solution 0.146% (Photrexa Viscous) and Riboflavin 5'-phosphate ophthalmic solution 0.146% (Photrexa) are intended for use with the KXL system. Photrexa Viscous is used in all CXL procedures, whereas Photrexa is indicated for use when the corneal stroma is thinner than 400 µm after completion of the Photrexa Viscous induction period. The FDA-approved procedure using the Dresden protocol (UV-A, 3 mW/cm for 30 min) induces cytologic and morphologic changes in the anterior 250 to 300 µm of the corneal stroma. It has been believed that a minimum thickness of 400 μm was necessary to protect the corneal endothelium from potential damage. The CXL procedure using the standard Dresden protocol is established as the gold standard for treatment of progressive keratoconus. CXL treatment is indicated for a list of conditions ranging from corneal ectasia to infectious keratitis. Newer protocols, treatment regimens, and expanded indications will require further refinements, investigations, and long-term studies.

[Indexed for MEDLINE]

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