Abstract
Abstract: :
Purpose: The cornea is a primary barrier to the entrance of bacteria into the eye. Rapid restoration of epithelial integrity after trauma, surgical procedure or during chronic inflammation is essential for visual acuity. This study assessed the impact of the new IVth generation fluoroquinolones gatifloxacin and moxifloxacin on corneal wound healing in a rabbit model of anterior keratectomy (AK). Methods: Female NZW rabbits (2.5–3.0 kg) were randomly divided into 3 groups (n=6/group) after 8 mm central corneal AK performed on both eyes. Rabbits were topically treated (t.i.d.) with 0.3% gatifloxacin (Gati) (Zymar, Allergan, Inc.), 0.5% moxifloxacin (Moxi) (Vigamox, Alcon Laboratories, Inc.) or the vehicle of Gati after AK until day 5. Digital slit lamp microscopy was performed immediately post AK for the base value of epithelial wounding and twice a day (at 9 and 4 pm) until day 5. Corneas from half of the rabbits were collected at 48 hours. The remaining half was collected on day 5 (at 96 hours). The rate of corneal re–epithelialization was assessed by an imaging software (ImagePro Plus) to determine epithelial defect area at each time point over the baseline wound value as a function of time. The quality of epithelial healing was evaluated by the distribution and quantity of type IV collagen expression using immunohistochemistry and Western blot. Results: When compared with the vehicle, topical Gati caused no significant delay or acceleration in the rate of epithelial healing. In contrast, Moxi delayed wound closure during the linear phase (6 hours post–AK) of epithelial healing. Significant delay of 13.25%, 15.76% and 16.49% by Moxi as compared with the vehicle was detected at 72, 78 and 96 hours post–AK respectively. Additionally, in the Moxi–treated rabbit corneas, collagen IV expression was markedly diminished, especially after the leading edge of the wound in the basement membrane at 48 and 96 hours. Quantitative analysis of collagen IV proteins from newly migrating corneal epithelial cells revealed a significant 30.5% decrease by Moxi as compared with Gati. Conclusions: Topical Zymar treatment did not delay corneal epithelial healing nor decrease collagen IV expression after AK. In contrast, topical Vigamox treatment on post–AK rabbit corneas resulted in delayed epithelial healing rate. This delay is likely due to suppression in collagen IV expression in the migrating corneal epithelial cells. This finding, if confirmed by others, raises concern for epithelial cell adhesion, and resultant abnormal and delayed healing of corneal lesions.
Keywords: cornea: epithelium • wound healing • antibiotics/antifungals/antiparasitics