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Toxicity of Intracameral Injection of Fourth-Generation Fluoroquinolones on the Corneal Endothelium

e Silva, Francisco Bandeira MD; Carrijo-Carvalho, Linda Christian PhD; Teixeira, Anderson MD; de Freitas, Denise PhD; Carvalho, Fabio Ramos de Souza PhD

doi: 10.1097/ICO.0000000000000967
Basic Investigation
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Purpose: 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.

Method: 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.

Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo, São Paulo, Brazil.

Reprints: Francisco Bandeira e Silva, MD, Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo, Botucatu St, 822, Vila Clementino, Sao Paulo, SP 04023-062, Brazil (e-mail: franciscobandeira@me.com).

Supported by São Paulo Research Foundation (FAPESP) grants 2008/53969-0 (D.de.F.) and 2011/51626-1 (F.R.de.S.C.) and Coordination for the Improvement of Higher Education Personnel (CAPES) grant 23038.001063/2012-01 (L.C.C-C.). L. C. Carrijo-Carvalho receives funding from PNPD/CAPES. F. R. de. S. Carvalho receives funding from Young Researchers at Emerging Centers Program of FAPESP (grant 2012/15603-0). D. de Freitas receives funding from the National Council for Scientific and Technological Development (CNPq, grant 311612/2012-1).

The authors have no conflicts of interest to disclose.

Presented in part at the Association for Research in Vision and Ophthalmology 2014 Annual Meeting, May 5, 2014, Orlando, FL.

Ethical approval was granted by the ethics committee of Federal University of Sao Paulo (UNIFESP), with approval registered under the code 2223161013.

Received April 08, 2016

Received in revised form June 01, 2016

Accepted June 10, 2016

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