Phototoxic Effect of Topical Fluoroquinolones Administered before Corneal Crosslinking in a Murine Model

Victor E. Reviglio, Matias Osaba, Gabriela Sambuelli, Irene C Kuo

Research output: Contribution to journalArticlepeer-review


Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalJournal of Ocular Pharmacology and Therapeutics
Issue number2
StatePublished - Mar 1 2017


  • apoptosis
  • corneal crosslinking
  • fluoroquinolones
  • riboflavin
  • UV phototoxicity

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)


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