Adhesion of laser in situ keratomileusis-like flaps in the cornea: Effects of crosslinking, stromal fibroblasts, and cytokine treatment

J Cataract Refract Surg. 2011 Jan;37(1):166-72. doi: 10.1016/j.jcrs.2010.07.028.


Purpose: To evaluate 3 approaches, both cellular and acellular, to improve the healing of laser in situ keratomileusis flaps in bovine corneas.

Setting: School of Optometry and Vision Sciences and Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom.

Design: Experimental study.

Methods: Laser in situ keratomileusis-like flaps were created in bovine corneas, and the flap bed was treated with tumor necrosis factor-α, interleukin-1α, Fas ligand, transforming growth factor-β(1), or activated stromal fibroblasts. In separate experiments, flaps were created and repositioned. The corneas were then crosslinked using ultraviolet-A (UVA) light. All samples were then placed in organ culture for up to 4 weeks. Untreated samples acted as controls.

Results: All treatments increased the adherence of the stromal flap. This was achieved at the expense of corneal clarity except in the case of crosslinking (CXL). In this case, the flap adhesion force immediately increased while the cornea remained clear. The force then decreased gradually during organ culture, although it remained at twice the level of the control corneas after 3 weeks in culture.

Conclusions: The results suggest that riboflavin-UVA CXL is a hopeful approach for increasing the adherence strength of corneal flaps while keeping the cornea clear. Further studies are necessary to confirm the durability of the strengthening effect and to exclude serious late complications.

Financial disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Count
  • Cornea / drug effects
  • Cornea / physiology*
  • Cornea / surgery
  • Corneal Stroma / cytology
  • Cross-Linking Reagents / pharmacology*
  • Cytokines / pharmacology*
  • Fas Ligand Protein / pharmacology
  • Fibroblasts / physiology*
  • Immunohistochemistry
  • Interleukin-1alpha / pharmacology
  • Keratomileusis, Laser In Situ*
  • Lasers, Excimer
  • Models, Biological
  • Organ Culture Techniques
  • Photosensitizing Agents / pharmacology
  • Surgical Flaps*
  • Tissue Adhesions
  • Transforming Growth Factor beta1 / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Ultraviolet Rays
  • Wound Healing / physiology*


  • Cross-Linking Reagents
  • Cytokines
  • Fas Ligand Protein
  • Interleukin-1alpha
  • Photosensitizing Agents
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha