In vivo toxicity of netilmicin and ofloxacin on intact and mechanically damaged eyes of rabbit.

PURPOSE: To evaluate the in vivo toxicity of netilmicin and ofloxacin using both normal and mechanically damaged eyes of rabbit. METHODS: Male albino New Zealand rabbits were given either 0.3% netilmicin, 0.3% ofloxacin, or 0.9% sodium chloride solution by topical instillation (50 microL) into the conjunctival sac 6 times daily for 5 days. In some animals a 6-mm-diameter epithelial wound was mechanically made to the center of the cornea. Ocular toxicity on normal eyes was evaluated by impression cytology of the conjunctiva, histology of the entire globes, and scanning electron microscopy (SEM) of the cornea. Analysis of toxicity and reepithelialization on wounded corneas was evaluated by SEM with observations being made 48 and 72 hours after induction of the wound. RESULTS: Cytologic, histopathologic, and SEM analyses of normal healthy eyes following netilmicin treatment revealed no signs of toxicity, whereas those treated with ofloxacin revealed alterations in the cornea (stromal swelling) and conjunctiva (infiltration of polymorphonuclear cells) with reduced goblet cell numbers. Wounded corneas treated with netilmicin exhibited normal morphology and reepithelialization, whereas the administration of ofloxacin resulted in disordered cellular organisation and slower rates of epithelial recovery. CONCLUSIONS: Netilmicin, an antibacterial aminoglycoside, is well tolerated even in an experimental wound-healing model where the integrity of the ocular surface is compromised, whereas ofloxacin, a fluoroquinolone, appears to provoke an inflammatory response in the normal eye and a clear alteration of reepithelialization in the wounded eye. These findings suggest that netilmicin may offer a superior toxicological profile in both normal eyes and clinical situations where the integrity of the ocular epithelium is suspect.

In vitro toxicity of netilmicin and ofloxacin on corneal epithelial cells.

PURPOSE: To evaluate the in vitro cytotoxic effect of the aminoglycoside antibiotic netilmicin on rabbit corneal epithelial cells (SIRC) compared with ofloxacin, a commonly used fluoroquinolone ocular antibiotic. METHODS: SIRC cell cultures were incubated for 8 to 72 h in the presence and absence of netilmicin (1.5, 3, and 6 mg/mL) and equal concentrations of ofloxacin. Cell viability in treated and untreated SIRC cells was measured by both neutral red and MTT colorimetric assays at 8, 24, and 72 h, whereas changes in cell morphology were examined at 8, 24, 48, and 72 hours by the use of phase-contrast microscopy. RESULTS: Netilmicin, at all tested concentrations, failed to alter SIRC cell viability or morphology. In contrast, all concentrations of ofloxacin caused statistically significant dose- and time-dependent reductions in cell viability even after 8 h. After 72 h there was complete loss of cell viability. Morphologic examination of SIRC cells after 8 h of incubation with ofloxacin revealed that the fluoroquinolone antibiotic, at all concentrations, produced large numbers of dead cells, compromised intercellular contacts, and altered general morphology. After 48 h the cell monolayer was observed to be completely destroyed. CONCLUSION: Netilmicin, at the concentrations used, is an antibiotic devoid of obvious cellular toxicity and may also be considered as a suitable first-choice drug in the treatment of those pathologies that compromise the integrity of the ocular surface.