The development of corneal opacity, increased hydration and increased thickness in isolated porcine corneas in response to timolol maleate solutions containing various preservatives

By Igarashi, H. - Sato, C. - Chiba, Y. - Ogawa, K. - Kojima, M.

The effects of 0.125%, 0.25% and 0.5% timolol maleate on the opacity, thickness and hydration of isolated porcine corneas were determined. The effects of adding 0.005% benzalkonium chloride, 0.5% chlorbutanol or a combination of 0.026%, methyl p-hydroxybenzoate, 0.014% propyl p-hydroxybenzoate and 0.2%; chlorbutanol to the timolol solutions were also assessed. Over a 4-hour incubation period, a concentration-related opacity developed in the presence of timolol alone, and was not greatly affected by the addition of the p-hydroxybenzoate mixture. However, the addition of benzalkonium chloride or the higher concentration of chlorbutanol markedly increased opacity. Corneal thickness increased significantly in the presence of 0.25% and 0.5% timolol and even further in the presence of the preservatives, chlorbutanol being the most potent. Hydration increased slightly with time and also in the presence of each of the preservatives. The need to achieve a balance between possible corneal toxicity and effective bactericidal activity is discussed.