title: Riboflavin-UV--a crosslinking for fixation of biosynthetic corneal collagen implants.
abstract: OBJECTIVE
  To evaluate riboflavin-UV-A crosslinking as an alternative suture-free fixation method for biosynthetic corneal collagen implants.
  
  
  METHODS
  A range of cell-free corneal implants consisting of recombinant human collagen type III were examined. In vitro, the implants were crosslinked with different riboflavin solutions and irradiations. Ex vivo, the biosynthetic corneal implants were placed on the anterior cornea of porcine and rabbit eyes after performing deep anterior lamellar keratoplasty with a trephine, femtosecond laser, or excimer laser. UV-A crosslinking was performed with isotonic or hypotonic riboflavin at either standard or rapid procedure. The corneas were excised, fixed in PFA 4%, and embedded in paraffin. Crosslinking effects on the implants and the adhesion between implant and corneal bed were evaluated by slit-lamp biomicroscopy, optical coherence tomography (OCT) images, and histologically.
  
  
  RESULTS
  After the crosslinking procedure, the implants showed different degrees of thinning. The accuracy of cutting the corneal bed was highest with the excimer laser. Good adhesion of the implant in the corneal bed could be demonstrated in OCT images. This was more accurate in porcine eyes than in rabbit eyes. Histologically, crosslinks between implant and corneal stroma were demonstrated. There was no difference between standard and rapid crosslinking procedures.
  
  
  CONCLUSIONS
  Riboflavin-UV-A crosslinking as a fixation method for biosynthetic corneal collagen implants was demonstrated to be promising. It can reduce suture-related complications such as haze formation and surface irregularity. Stability of the implants, especially shrinkage after riboflavin-UV-A crosslinking, needs to be further evaluated. Biostability, integration, and long-term outcome are further evaluated in in vivo animal experiments.
authors.affiliation: *Department of Ophthalmology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; †MLase AG, Germering München, Munich, Germany; ‡Technolas PV Bausch & Lomb, Munich, Germany; and §Department of Clinical and Experimental Medicine and Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wand
authors.forename: Raphael
authors.initials: R
authors.lastname: Neuhann
authors.forename: Andrea
authors.initials: A
authors.lastname: Ullmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Plank
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Roland
authors.initials: R
authors.lastname: Ritter
authors.forename: May
authors.initials: M
authors.lastname: Griffith
authors.forename: Chris P
authors.initials: CP
authors.lastname: Lohmann
authors.forename: Karin
authors.initials: K
authors.lastname: Kobuch
mesh_terms: D000818:Animals; D024061:Collagen Type III / Q000138:chemical synthesis / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents / Q000494:pharmacology*; D019736:Prostheses and Implants; D019919:Prosthesis Implantation / Q000379:methods*; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology*; D013552:Swine; D014466:Ultraviolet Rays
chemical_list: D024061:Collagen Type III; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012256:Riboflavin