BASIC INVESTIGATION
Effect of Fourth-Generation Fluoroquinolones on the
Healing Rate of Corneal Erosions in an Animal Model
Irina S. Barequet, MD, Zohar Habot-Wilner, MD, Fabio Lavinsky, MD, Hana Ziv, MSc,
Michael Belkin, MD, and Mordechai Rosner, MD
Purpose: To compare the rate of epithelial healing of corneal ero-
sion in an animal model with 2 commercial formulations of fourth-
generation fluoroquinolones: 0.3% gatifloxacin and 0.5% moxifloxacin.
Methods: Corneal erosions, 6 mm in diameter, were created in
28 rabbit eyes. The rabbits were randomized to receive topical
gatifloxacin, moxifloxacin, or nonpreserved saline. Drops were
administered every 15 minutes for 1 hour, then hourly for 3 hours,
and then 4 times daily until the erosion reepithelialized. Eyes were
examined with fluorescein drops and photographed every 12 hours
with a cobalt blue–filtered light. When reepithelialization was
observed, the rabbits were euthanized, and their eyes were enucleated
for histopathologic evaluation.
Results: Reepithelialization of the corneal erosions was fastest in
the saline-treated eyes (57.3 6 8 hours), followed by moxifloxacin
(62.7 6 11.7 hours) and gatifloxacin (66 6 8.5 hours). These dif-
ferences in the time to closure of the erosions among the 3 groups
were not statistically significant. Although significant differences
were found among the healing progression curves when all 3 groups
were compared (P = 0.042), the difference between the 2 antibiotic-
treated groups was not significant.
Conclusions: Only slight differences in epithelial healing rates were
found between the gatifloxacin-, moxifloxacin-, and saline-treated
groups, suggesting that the 2 fluoroquinolones may have an equiva-
lent role as prophylactic treatment of trauma- or surgery-induced
corneal erosions.
Key Words: corneal erosion, fluoroquinolones, fourth-generation
fluoroquinolones, prophylaxis in corneal erosions, gatifloxacin,
moxifloxacin
(Cornea 2007;26:606–609)
B
acterial keratitis is the most serious and potentially
devastating complication of corneal erosion caused either
by trauma or during photorefractive keratectomy (PRK) or
phototherapeutic keratectomy (PTK).
1,2
To reduce this risk,
prophylactic antibiotics should be administered immediately
after the traumatic event or surgery and continue until epi-
thelial healing is completed.
The 2 topical fourth-generation fluoroquinolones, gati-
floxacin 0.3% ophthalmic solution (Zymar; Allergan, Irvine,
CA) and moxifloxacin 0.5% ophthalmic solution (Vigamox;
Alcon Laboratories, Fort Worth, TX), have become increas-
ingly popular for prophylaxis.
3
Selection of the most
appropriate antibiotic is usually from considerations such
as spectrum of microbial coverage, bioavailability, ocular
tolerance, and cost. When there is no clear evidence to support
the superiority of 1 drug over another in these respects, addi-
tional factors may be considered. For the fourth-generation
fluoroquinolones, subtle differences in the mechanism of
action, concentration, vehicle, pH, solubility, and preservative
of each compound may lead to a potential difference in their
effect on epithelial healing. Such a difference may have
implications for the selection of antibiotic prophylaxis after
erosion of the cornea caused by trauma, by refractive surgery
such as PRK and PTK, or by penetrating keratoplasty.
Faster epithelial healing accelerates visual recovery,
allows patients to return to work and other daily activities
sooner, and reduces the risk of adverse events such as
infection. Because recent clinical studies on epithelial healing
in patients treated by fourth-generation fluoroquinolones have
thus far produced controversial results,
4–6
we carried out this
study in an animal model to examine the epithelial healing
after corneal erosion in eyes treated with the commercial
formulations of gatifloxacin or moxifloxacin relative to saline.
MATERIALS AND METHODS
Thirty New Zealand White male rabbits weighing 2–3 kg
were kept in wire mesh cages and fed with standard pelleted
chow and tap water. All procedures were performed in
accordance with the ARVO statement for the Use of Animals
in Ophthalmic and Visual Research, and the experimental
protocol was approved by the Institutional Animal Care and
Use Committee of Tel-Aviv University. The rabbits were anes-
thetized by intramuscular injection of a mixture of 0.5 mg/kg
ketamine (Ketaset, 100 mg/mL; Animal Health, Fort Dodge,
IA) and 10 mg/kg xylazine (Chanazine, 20 mg/mL; Chanelle
Pharmaceuticals Manufacturing, Loughrea, Co. Galway,
Ireland) before corneal erosions were induced, and by one
half of these doses before each examination and photography.
Before enucleation of the eyes at the conclusion of the study,
the anesthetized rabbits were euthanized by an intracardiac
injection of pentobarbital (60 mg/mL).
Received for publication September 17, 2006; revision received January 29,
2007; accepted January 30, 2007.
From the Goldschleger Eye Institute, Sheba Medical Center, Sackler Faculty
of Medicine, Tel Aviv University, Tel Hashomer, Israel.
Reprints: Irina S. Barequet, Goldschleger Eye Institute, Sheba Medical Center,
Tel Hashomer 52621, Israel (e-mail: barequet@cs.technion.ac.il).
Copyright Ó 2007 by Lippincott Williams & Wilkins
606 Cornea
Volume 26, Number 5, June 2007
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.