title: Keratoconus and crosslinking: pharmacokinetic considerations.
abstract: BACKGROUND
  Keratoconus (KC) is an ectatic disorder characterized by the progressive thinning and scarring of central cornea as a consequence of structural and/or compositional anomalies, although the exact etiology is largely unknown. The resultant conical protrusion of the cornea causes significant irregular astigmatism, myopia and visual impairment.
  
  
  METHODS
  This paper will review the biochemical factors involved in the multifactorial pathogenesis of KC and the possible emerging role of inflammation in this process. Additionally, the authors discuss the development of new corneal collagen crosslinking (CCL) protocols using hypoosmolar riboflavin or transepithelial approaches with respect to the associated toxicities at the cellular level.
  
  
  CONCLUSIONS
  Long-term consequences of standard and new emerging CCL protocols are still being studied; hence, pharmacokinetic considerations and related potential toxicities are important to consider. CCL sequentially combined with other modalities, specifically intrastromal corneal ring segments and photorefractive keratectomy can optimize the visual rehabilitation of KC patients. As we come to further understand CCL and its pharmacokinetic effects, additional indications for CCL may be discovered especially for those patients who are not suitable candidates for keratoplasty. Randomized control trials evaluating the efficacy of CCL for applications beyond halting KC disease progression are warranted.
authors.affiliation: University of Toronto, Department of Ophthalmology and Vision Sciences , 601 - 600 Sherbourne Street, Toronto, Ontario, M4X 1W4 , Canada +1 416 960 5007 ; +1 416 960 0333 ; clarachanmd@gmail.com.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chan
authors.forename: Victoria
authors.initials: V
authors.lastname: Squissato
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001548:Benzalkonium Compounds / Q000009:adverse effects; D003094:Collagen / Q000493:pharmacokinetics*; D003315:Cornea / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000166:cytology / Q000528:radiation effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007640:Keratoconus / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012256:Riboflavin / Q000493:pharmacokinetics*; D015398:Signal Transduction; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D001548:Benzalkonium Compounds; D015850:Interleukin-6; D003094:Collagen; D012256:Riboflavin