Toxicity of 0.2% chlorhexidine gluconate on the cornea and adjacent structures

Vicente Victor Ocampo Jr., MD1, 2 Ellen Yu, MD1,3 Tongzhen Zhao, MD1 Agha Hassan Feroze4 C. Stephen Foster, MD, FACS1


To determine the toxicity of the potential fungicide chlorhexidine gluconate (as a pure 0.2% solution and as a commercially available skin antiseptic diluted to contain 0.2% chlorhexidine gluconate) to the cornea and adjacent ocular structures.


An experimental study was performed at the Animal Facility of the Massachusetts Eye and Ear Infirmary. Pure chlorhexidine gluconate 0.2% was applied to the right eye of 10 female albino rabbits 4 times daily for 14 days. Prior to treatment, all eyes underwent debridement of the corneal epithelium and were examined on days 1, 3, 7, and 14. The toxicity of the following was also determined: a commercial skin antiseptic solution diluted to contain 0.2% chlorhexidine gluconate and 0.2% isopropyl alcohol as active ingredients (4), 0.2% isopropyl alcohol (3), and sterile distilled water (2). The acute toxicity of the diluted solution was determined by application every hour for 6 hours. Histopathological examination was done.


Complete reepithelialization was noted by the seventh day in all eyes. At day 14, all corneal epithelia remained intact, but mild superficial punctate keratopathy was observed in some eyes treated with pure 0.2% chlorhexidine, in all eyes treated with the diluted solution and distilled water, but none in alcohol-treated eyes. Histopathological examination revealed no signs of corneal inflammation in 6 of 10 eyes treated with pure chlorhexidene. Very mild inflammation was noted in the remaining 4 eyes, and in all eyes treated with the diluted solution, 0.2% isopropyl alcohol, and sterile distilled water. Acute toxicity studies using the diluted solution applied hourly showed mild inflammation not only of the anterior corneal stroma (2 of 3 eyes) but also of the sclera (1 of 3 eyes).


Multiple applications of 0.2% chlorhexidine gluconate as a pure solution and as a diluted skin-antiseptic solution did not produce severe inflammation and structural alterations in the deep layers of the cornea in rabbit eyes. This suggests that the solutions may be safe for alternative use in the prolonged and intensive treatment of filamentous keratomycosis.

Keywords: Chlorhexidine, Toxicity, Cornea, Keratomycosis, Keratitis