Effects of fourth-generation fluoroquinolones on the ocular surface, epithelium, and wound healing

PURPOSE: To compare the cellular effects of gatifloxacin and moxifloxacin on multidimensional aspects of corneal wound healing. METHODS: Several animal models were used to evaluate the effect of commercial preparations of gatifloxacin ophthalmic solution 0.3% (Zymar) and moxifloxacin ophthalmic solution 0.5% (Vigamox) on the rate and quality of corneal wound healing. These included an in vivo rabbit anterior keratectomy model, a central corneal full-thickness incision model, and a model of the inflammation associated with experimental dry eye in mice. An in vitro normal human conjunctival epithelial cell culture model was also evaluated. RESULTS: Despite the presence of benzalkonium chloride (BAK) in its formulation, gatifloxacin caused less degradation of corneal epithelial barrier function than moxifloxacin did. Moxifloxacin inhibited collagen IV synthesis to a greater extent than did gatifloxacin, and transmission electron microscopy revealed loss of normal structure in the basal lamina of moxifloxacin-treated eyes. Incisional healing in eyes treated with moxifloxacin was slower and more disorganized than in eyes treated with gatifloxacin or vehicle. In the gatifloxacin-treated cultures, the normal human conjunctival cells continued to grow and appeared most like the vehicle-treated cultures. Conversely, moxifloxacin inhibited cell proliferation. CONCLUSION: Taken together, the studies presented here provide evidence that moxifloxacin has a deleterious effect on both the speed and quality of corneal wound healing, whereas gatifloxacin does not. The clinical relevance of these data needs to be evaluated further.