title: Microbiologic, Pharmacokinetic, and Clinical Effects of Corneal Collagen Cross-Linking on Experimentally Induced Pseudomonas Keratitis in Rabbits.
abstract: OBJECTIVE
  To determine the effects of corneal collagen cross-linking (CXL) on the penetration of topical 0.5% moxifloxacin, on the number of colony-forming units (CFUs) in the cornea, and on the clinical course in a rabbit eye model of experimentally induced Pseudomonas aeruginosa keratitis.
  
  
  METHODS
  In this prospective animal study, experimental Pseudomonas corneal ulcers were induced in 56 corneas of 28 albino New Zealand rabbits. The corneas were randomly divided into the following 4 groups: the control group (14 eyes), the MOX group (moxifloxacin) (14 eyes), the MOX + CXL group (14 eyes), and the CXL group (14 eyes). On day 4 of the experiment, the eyes in the control group were enucleated and CFU counting was performed. On day 10 of the experiment, all eyes were enucleated and CFU counting was performed. In the MOX and MOX + CXL groups, the moxifloxacin level in the cornea, aqueous humor, iris, plasma, and serum was measured by reverse-phase high-performance liquid chromatography.
  
  
  RESULTS
  The difference in the corneal CFU count between the MOX group and the MOX + CXL group was not significant (P = 0.317). Clinical improvement was greatest in the MOX + CXL group (P < 0.001). The mean corneal moxifloxacin level was 0.391 ± 0.09 μg·mg in the MOX group versus 0.291 ± 0.09 μg·mg in the MOX + CXL group; as such, CXL did not have a significant effect on antibiotic penetrance (P = 0.386).
  
  
  CONCLUSIONS
  Clinical improvement was greatest in the MOX + CXL group. The synergistic effect of CXL on corneal ulcer treatment is not through antibiotic penetrance.
authors.affiliation: *Department of Ophthalmology, Acibadem University, Istanbul, Turkey; †Biology of Lab Animals & Biomedical Application Techniques, Experimental Medicine Research Institute, Istanbul University, Istanbul, Turkey; ‡Department of Ophthalmology, Namik Kemal University, Tekirdag, Turkey; Departments of §Microbiology, and ¶Biochemistry, Acibadem University, Istanbul, Turkey; and ‖Department of Pathology, Acibadem Maslak Hospital, Istanbul, Turkey.
authors.forename: C Banu
authors.initials: CB
authors.lastname: Cosar
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.forename: Ekrem
authors.initials: E
authors.lastname: Celik
authors.forename: Tansu
authors.initials: T
authors.lastname: Gonen
authors.forename: Isin
authors.initials: I
authors.lastname: Akyar
authors.forename: Mustafa
authors.initials: M
authors.lastname: Serteser
authors.forename: Fatma
authors.initials: F
authors.lastname: Tokat
authors.forename: Umit
authors.initials: U
authors.lastname: Ince
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D003094:Collagen / Q000378:metabolism*; D015169:Colony Count, Microbial; D003315:Cornea / Q000382:microbiology; D003319:Corneal Stroma / Q000378:metabolism*; D003320:Corneal Ulcer / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D003432:Cross-Linking Reagents; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D000077266:Moxifloxacin; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D011817:Rabbits; D012256:Riboflavin / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin; D000077266:Moxifloxacin