title: Cellular effects after laser in situ keratomileusis flap formation with femtosecond lasers: a review.
abstract: OBJECTIVE
  To provide an overview of the cellular effects of femtosecond laser in laser in situ keratomileusis flap formation.
  
  
  METHODS
  Literature review.
  
  
  RESULTS
  The IntraLase is the only femtosecond laser with sufficient histopathological and confocal studies to allow review of the cellular effects of laser application. Histopathological analyses have demonstrated that the energy per pulse and total energy delivered play important roles in the inflammatory reaction to the surgery. The IntraLase laser triggers cellular necrosis (death accompanied by the release of lysosomal enzymes and other components from membrane-bound intracellular compartments) in the corneal stroma surrounding the lamellar cut rather than apoptosis (gentler form of cell death in which most intracellular components remain confined to membrane-bound apoptotic bodies) that is predominant with the microkeratome. Necrosis is a more inflammatory form of cell death that attracts more inflammatory cells. This is likely why earlier femtosecond lasers, such as the 15-kHz IntraLase laser, which requires higher total energy delivery to cut a flap, are associated with more corneal inflammation and diffuse lamellar keratitis. The design of the 60-kHz IntraLase model allows for much lower energy delivery to cut the flap and, therefore, a substantial reduction in keratocyte necrosis to the point that the overall inflammatory response is not significantly different from the microkeratome. Histopathological analysis performed with the Femtec femtosecond laser noted little change in the corneal stromal structure. Confocal microcopy studies performed with the IntraLase laser showed keratocyte "activation" in the stroma and greater fibrotic scarring at the interface than that induced by a mechanical microkeratome.
  
  
  CONCLUSIONS
  The morphologic alterations in the corneal stroma produced by currently available models of the IntraLase laser are comparable to those produced by mechanical microkeratomes. Advances that have resulted in a reduction in the total amount of energy delivered by the laser when it cuts the flap have resulted in a decrease in the inflammatory response associated with femtosecond flap formation to the point that it is indistinguishable from the microkeratome at the cellular level. Further study of each of the femtosecond laser models, including the 150-kHz IntraLase laser, is needed to fully characterize the corneal response to these lasers.
authors.affiliation: Cole Eye Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Marcony R
authors.initials: MR
authors.lastname: Santhiago
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wilson
mesh_terms: D003315:Cornea / Q000473:pathology / Q000601:surgery*; D003319:Corneal Stroma / Q000473:pathology / Q000601:surgery; D006801:Humans; D020731:Keratomileusis, Laser In Situ / Q000379:methods*; D012030:Refractive Errors / Q000473:pathology / Q000628:therapy*; D013524:Surgical Flaps