Delayed corneal wound healing resulting from the administration of fluoroquinolone antibacterial ophthalmic solutions and its causes

Abstract

Purpose: The purpose of this study was to examine delayed corneal wound healing resulting from the administration of fluoroquinolone antibacterial ophthalmic solutions and the factors affecting this delay.

Methods: Corneal epithelial detachment was induced in mature domestic white rabbits (male, weight: 2.5-3.0kg) with 1-heptanol and these rabbits were subsequently used in the experiment. Three types of antibacterial ophthalmic solutions, VEGAMOXTM 0.5% ophthalmic solution (MFLX), Cravit® 1.5% ophthalmic solution (LVFX), and Gatifloxacin® 0.3% ophthalmic solution (GFLX), were used in this experiment where rabbit models were divided into antibacterial agent instillation groups and a saline solution instillation group (control) and the impact on corneal wound healing was assessed using a corneal electrical resistance measurement method (corneal resistance device: CRD method). Seven eye drops were instilled every 30 minutes following corneal epithelial abrasion and corneal resistance CR(%) was measured from 1-96 hours following the completion of instillation. The degree of corneal disorder was assessed with fluorescein staining. The effect of each antibacterial agent on cell proliferation was also assessed using rabbit-derived corneal cell lines (SIRC).

Results: CR(%) as measured by the CRD method increased along with the reduction in the fluorescein staining area. There was significant reduction in the CR(%) of the three antibacterial ophthalmic solution groups as compared to the control group (P<0.05) and corneal wound healing was delayed. It is possible that the CRD method can detect disorder that cannot be evaluated by fluorescein staining. There was a significant reduction in the cell proliferation rate (%) in the LVFX and MFLX groups as compared with the control group (P<0.05), however there was no significant reduction in the GFLX group.

Conclusions: Delayed corneal wound healing resulting from the administration of three antibacterial ophthalmic solutions could be confirmed. The cause of this is believed to be the suppression of corneal cell proliferation as a consequence of the DNA synthesis inhibitory effect of the antibacterial agent along with the increase in concentration of the ophthalmic solutions.

Keywords: 422 antibiotics/antifungals/antiparasitics • 482 cornea: epithelium • 765 wound healing