title: Toxicity of Intracameral Injection of Fourth-Generation Fluoroquinolones on the Corneal Endothelium.
abstract: OBJECTIVE
  The aim of this study was to compare the cellular susceptibility patterns and morphologic changes in the corneal endothelium associated with the use of fourth-generation fluoroquinolones.
  
  
  METHODS
  Endothelial susceptibility was assessed through intracameral injection of besifloxacin, gatifloxacin, and moxifloxacin. Human umbilical vein endothelial cells (HUVECs) were used as the standard cellular lineage to assess the quantitative toxicity of each antibiotic solution. Qualitative changes in the morphologic character of the corneal structure and the endothelial layer were generated using a combination of ex vivo and in vivo assays. Experimental assays were conducted in triplicate, and the results were statistically analyzed.
  
  
  RESULTS
  At 1 hour of exposure, all HUVECs exposed to antibiotics showed viability above 85%, after 3 hours of exposure to besifloxacin, gatifloxacin, and moxifloxacin, the percentages of viable cells were 68.3 ± 4.0 (P < 0.001), 90.7 ± 4.2 (P < 0.05), and 93.3 ± 1.5 (P > 0.05), respectively. All fluoroquinolones tested showed toxicity to HUVECs, resulting in significant (P < 0.001) loss of cellular viability after 24 hours of drug exposure. Giant endothelial cells were observed in animals treated with the 3 fluoroquinolones in contrast to the absence of these abnormal cells in the untreated group. Early cellular detachment was seen in the endothelial layer after exposure to gatifloxacin and moxifloxacin.
  
  
  CONCLUSIONS
  We concluded that injection of fourth-generation fluoroquinolones in the aqueous humor did not adversely affect the corneal endothelium. However, these results suggested that prophylactic intracameral injection of besifloxacin, gatifloxacin, or moxifloxacin, if needed, should be administered as a last therapeutic resource in clinical practice, with careful and constant monitoring of corneal endothelium.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo, São Paulo, Brazil.
authors.forename: Francisco Bandeira
authors.initials: FB
authors.lastname: E Silva
authors.forename: Linda Christian
authors.initials: LC
authors.lastname: Carrijo-Carvalho
authors.forename: Anderson
authors.initials: A
authors.lastname: Teixeira
authors.forename: Denise
authors.initials: D
authors.lastname: de Freitas
authors.forename: Fabio Ramos de Souza
authors.initials: FR
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001082:Aqueous Humor / Q000187:drug effects; D001381:Azepines / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000473:pathology; D024841:Fluoroquinolones / Q000633:toxicity*; D000077734:Gatifloxacin; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D056965:Injections, Intraocular; D008297:Male; D000077266:Moxifloxacin; D009883:Ophthalmic Solutions; D011817:Rabbits; D059005:Topoisomerase II Inhibitors / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D059005:Topoisomerase II Inhibitors; C522124:besifloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin