Fibrinogen, riboflavin, and UVA to immobilize a corneal flap--conditions for tissue adhesion

Invest Ophthalmol Vis Sci. 2012 Jun 26;53(7):4011-20. doi: 10.1167/iovs.12-9515.


Purpose: Laser-assisted in situ keratomileus (LASIK) creates a permanent flap that remains non-attached to the underlying laser-modified stroma. This lack of permanent adhesion is a liability. To immobilize a corneal flap, a protocol using fibrinogen (FIB), riboflavin (RF), and ultraviolet (UVA) light (FIB+RF+UVA) was devised to re-adhere the flap to the stroma.

Methods: A model flap was created using rabbit (Oryctolagus cuniculus) and shark (Squalus acanthias) corneas. Solutions containing FIB and RF were applied between corneal strips as glue. Experimental corneas were irradiated with long wavelength (365 nm) UVA. To quantify adhesive strength between corneal strips, the glue-tissue interface was subjected to a constant force while a digital force gauge recorded peak tension.

Results: In the presence of FIB, substantive non-covalent interactions occurred between rabbit corneal strips. Adhesiveness was augmented if RF and UVA also were applied, suggesting formation of covalent bonds. Additionally, exposing both sides of rabbit corneas to UVA generated more adhesion than exposure from one side, suggesting that RF in the FIB solution catalyzes formation of covalent bonds at only the interface between stromal molecules and FIB closest to the UVA. In contrast, in the presence of FIB, shark corneal strips interacted non-covalently more substantively than those of rabbits, and adhesion was not augmented by applying RF+UVA, from either or both sides. Residual RF could be rinsed away within 1 hour.

Conclusions: Glue solution containing FIB and RF, together with UVA treatment, may aid immobilization of a corneal flap, potentially reducing risk of flap dislodgement.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corneal Stroma / drug effects
  • Corneal Stroma / pathology
  • Corneal Stroma / surgery*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Fibrinogen / pharmacology*
  • Keratomileusis, Laser In Situ / methods*
  • Myopia / surgery
  • Photosensitizing Agents / therapeutic use
  • Rabbits
  • Riboflavin / pharmacology*
  • Surgical Flaps*
  • Tissue Adhesions / pathology
  • Tissue Adhesions / prevention & control*
  • Ultraviolet Rays
  • Ultraviolet Therapy / methods*
  • Wound Healing / drug effects


  • Photosensitizing Agents
  • Fibrinogen
  • Riboflavin