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In Vivo Toxicity of Netilmicin and Ofloxacin on Intact and Mechanically Damaged Eyes of Rabbit

Marino, Clara BSc; Paladino, Grazia Maria BSc; Scuderi, Anna Claudia BSc; Trombetta, Francesco; Mugridge, Kennet BSc; Enea, Vincenzo PhD

doi: 10.1097/01.ico.0000154233.56736.08
Basic Investigations

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 μL) 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.

From the R&D Department, SIFI SpA, Via Ercole Patti, 36 Lavinaio, 95020 Catania, Italy.

Received for publication February 11, 2004; revision received November 10, 2004; accepted November 20, 2004.

Reprints: Grazia Maria Paladino, SIFI SpA, Via Ercole Patti, 36 Lavinaio, 95020 Catania, Italy, (e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.