title: Phototoxic Effect of Topical Fluoroquinolones Administered Before Corneal Crosslinking in a Murine Model.
abstract: Corneal crosslinking by UV light (UV-CXL) has become a popular treatment for keratoconus and corneal ectasia. Fluoroquinolones (FQs), commonly administered topically before UV-CXL, are known to be phototoxic to the skin and lens. The purpose of this study was to investigate phototoxic effects of topical FQ treatment on murine corneas before UV-CXL, in which the corneal epithelium was kept intact.
  
  
  
  Murine corneas were treated with various antibiotics with or without riboflavin before UV-CXL. At 24 h, the animals were sacrificed, and the corneas were analyzed for histologic evidence of inflammation and apoptosis and for expression of apoptosis markers BAX and caspases 3 and 9 and for expression of matrix metalloproteinase 9 (MMP-9). Spectrofluorometric analysis was performed.
  
  
  
  Corneas treated with topical FQ with or without riboflavin before UV-CXL showed mild corneal stromal inflammation, apoptosis by both terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased expression of BAX gene and caspases 3 and 9 by densitometric analysis. Untreated corneas, corneas treated with azithromycin before UV-CXL, and corneas undergoing UV-CXL without any antibiotic or riboflavin pretreatment showed normal histology, no staining for apoptosis, and no increased production of apoptosis markers by polymerase chain reaction.
  
  
  
  The phototoxic effects of FQs on the cornea may lead surgeons to consider another antibiotic class for prophylaxis against infectious keratitis in UV-CXL. These effects, along with the known cytotoxic effects of FQs independent of UV radiation, may contribute to some of the complications of corneal UV-CXL. Dosage studies may be warranted.
authors.affiliation: 1 Departamento de Patología e Investigación Ocular, Facultad de Medicina, Universidad Católica de Córdoba , Córdoba, Argentina .|2 Instituto de la Visión Cerro , Sanatorio Allende Cerro, Córdoba, Argentina .
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reviglio
authors.affiliation: 1 Departamento de Patología e Investigación Ocular, Facultad de Medicina, Universidad Católica de Córdoba , Córdoba, Argentina .|2 Instituto de la Visión Cerro , Sanatorio Allende Cerro, Córdoba, Argentina .
authors.forename: Matias
authors.initials: M
authors.lastname: Osaba
authors.affiliation: 1 Departamento de Patología e Investigación Ocular, Facultad de Medicina, Universidad Católica de Córdoba , Córdoba, Argentina .
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sambuelli
authors.affiliation: 3 Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Kuo
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000633:toxicity*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000633:toxicity*; D012256:Riboflavin / Q000008:administration & dosage / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D012256:Riboflavin
keywords: UV phototoxicity; apoptosis; corneal crosslinking; fluoroquinolones; riboflavin