Levofloxacin 1.5% was approved for treating patients with bacterial keratitis. A lower concentration, levofloxacin 0.5% (Quixin, Vistakon Pharmaceuticals) was approved for bacterial conjunctivitis. Bezwada et al. reported recently (Curr Med Res Opin. 2008;24:419-424) that in an in vitro study, the drug was the least cytotoxic of the fluoroquinolones to human corneal keratocyte and endothelial cell cultures. In an vivo study carried out by Clark and colleagues (Cutaneous Ocular Toxicol. 2004;23:1-18), wound healing was observed in rabbits and primates at a dose of two drops four times a day for 4 days. The investigators reported that there were no adverse effects on the cornea, re-epithelialization, keratocyte structure and organization, or wound healing, Dr. Abelson explained. He is associate clinical professor of ophthalmology at Harvard Medical School and senior clinical scientist at Schepens Eye Research Institute, both in Boston.
To test the effects of intensive dosing of levofloxacin in humans, Ophthalmic Research Associates Inc., North Andover, MA, carried out a prospective single-center, investigator-masked study that included 48 healthy volunteers. Each participant received a total of 224 doses of the drug in the right eye for 14 days. From study days 1 to 3, one drop was administered every 30 minutes from 8 a.m. to 8 p.m., and one drop was administered at midnight and 2 a.m. for a total of 27 doses for each of the 3 days. From study days 4 to 14, one drop was administered every hour from 8 a.m. to 8 p.m. for a total of 13 doses per day.
The subjects were evaluated at baseline and on days 8, 15, and 21 (7-days post-dosing). The safety of the drug was tested after every 7 days of dosing and compared with baseline. The subjects were evaluated by specular microscopy for the endothelial cell density and the endothelial cell morphology, i.e., cell size variability and the percent of hexagonal cells. Pachymetry was performed to measure the central corneal thickness. Patients also were assessed by slit-lamp biomicroscopy and measurement of the visual acuity.
All variables evaluated at baseline and after intensive dosing showed that levofloxacin did not affect any of the factors studied. Dr. Abelson reported that the mean endothelial cell density values measured at baseline and after dosing were virtually identical, that is, 2,767 ± 317 cells/µm2 versus 2,786 ±295 cells/µm2 , respectively. The sizes of the endothelial cells also were almost identical; the coefficient of variation at baseline and after dosing was 31.4 ± 5.2 versus 31.8 ± 5.9, respectively. The mean percentages of hexagonal cells in the corneal endothelium at baseline were 59.8 ± 10.8 compared with 61.9 ± 11.3 after dosing. Finally, the mean corneal thickness at baseline was 560 ± 36 µm compared with 568 ± 46 µm after dosing.
"There were no clinically significant negative changes in any measured safety parameter, including the endothelial cell density and morphology, the central corneal thickness, the visual acuity, slit-lamp biomicroscopy, IOP, or dilated funduscopy. The adverse events that were related to administration of levofloxacin were dysgeusia in 30% of the volunteers, ocular irritation in 7%, and ocular pruritus in 6%," Dr. Abelson commented.
Based on those findings, Dr. Abelson concluded that intensive dosing with levofloxacin 1.5% does not adversely affect the corneal endothelium.