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The relationship of corneal epithelial defect size to drug penetration
D A Johnson1, K J Johns, R D Robinson
1Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
Objective:
To determine the relationship between corneal epithelial defect size and corneal penetration of a triazole antifungal drug in an animal model.
Methods:
Corneas of adult rabbits were débrided of epithelium 25%, 50%, 75%, or 100% of surface area; the untreated fellow eye served as a control. Tritiated saperconazole was applied to each cornea every 5 minutes for 1 hour. The animals were killed and the cornea and aqueous of each eye were assayed for radiolabel activity.
Results:
Removal of 25% of the corneal epithelium produced an increase in corneal saperconazole concentration compared with eyes with intact epithelium. Increasing epithelial defect size from 25% to 50% produced a ninefold increase in mean corneal drug concentration (P = .0001). There was no further increase in corneal drug levels in eyes with 75% or 100% epithelial defects. A similar threshold effect was observed in aqueous drug concentration between 25% and 50% débridement (P = .0001).
Conclusion:
In this experimental model, an apparent threshold was noted between 25% and 50% epithelial defect area, beyond which larger defects did not significantly increase drug penetration into the cornea or aqueous. This may be of clinical benefit in circumstances in which epithelial débridement is considered to enhance drug penetration.