A multiple endpoint analysis (MEA) approach on human reconstructed corneal epithelium (HCE) model has been applied to assess the biocompatibility (cytotoxicity and irritation potential) of medical devices (MD): ophthalmology literature clearly shows the need to better assess these products to exclude any potential chronic damage to the ocular surface. Preserved eye drops (Artelac Multidose, Optive multidose and Artelac Rebalance Multidose) and the same without preservative (Artelac Edo, Optive Unidose, Artelac Rebalance Unidose) and Thealoz Duo were tested after acute (24 h + 16 h post incubation) and repeated (2 applications/day for 72 h) exposure using BAK 0.01% as positive control on HCE. Cellular viability, trans-epithelial electrical resistance measurements, LDH release and occludin gene expression were evaluated for each product to discriminate the potential toxicity of preservatives. The BAK 0.01% toxicity on HCE was confirmed following both exposures. The analysis of the same parameters reveals that the 72 h exposure was suitable to identify toxicity and damages to the ocular surface even for 'soft' preserved MD. The results confirm the reliability, sensitivity and predictivity of the MEA on HCE in detecting subclinical signs of cellular toxicity: 'soft' preservatives resulted toxics suggesting that delayed toxicity should be integral part of the biocompatibility assessment of ophthalmic formulations intended for long-term use.
Keywords: BAK; Biocompatibility; HCE; Medical devices; Ocular surface; Preservative free eye drops; Soft preservatives; Toxicity.
Copyright © 2019. Published by Elsevier Inc.