Corneas isolated from the pig eyeball have been treated in vitro with varying concentrations of befunolol hydrochloride, in order to test the topical effect of befunolol on the cornea in terms of opacity. Experiments were carried out with the corneas treated as follows: intact, epithelium-removed, endothelium-removed, and both epithelium- and endothelium-removed. Solutions of the drug were applied to both epithelial and endothelial surfaces, to the epithelial surface only, or to the endothelial surface only. When the drug was applied either to both surfaces or to the endothelial surface only, there was a significant increase in opacity. However, when applied to the epithelial surface only, befunolol caused an insignificant increase in opacity as compared with that of control. It is suggested, therefore, that corneal opacity due to befunolol hydrochloride topically administered to the eye, is concerned mainly with the epithelium in cornea, since the drug is uncapable of passing barrier probably existing in surface layer of epithelium but it easily penetrates in corneal layers from endothelial side to attain reversely to epithelial cells. Thus, it is probable that the risk to induce opacity is minor in case that befunolol is topically given in drops to the eye.
The in vitro development of porcine corneal opacity induced by carbachol was monitored using a simple, specially constructed opacitometer. Corneas were used intact, without epithelium, or without endothelium, or stroma only. Solutions of carbachol were applied to both surfaces, to the epithelial surface only or to the endothelial surface only. When carbachol was applied either to both surfaces or to the epithelial surface only, there was a significant increase in opacity compared with controls in the order: both epithelium and endothelium removed>epithelium removed>endothelium removed>intact. However, when applied to the endothelial surface only of intact and endothelium-removed corneas, carbachol caused an opacity comparable to control values. This confirms that the drug is safe for use as a topical application in the eye. However, the opacity which develops in corneas in response to benzalkonium chloride indicates that great care must be taken in determining the optimal concentration to use as a “wetting agent”.
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