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MARISA MELONI, Francesco Ranzini, Barbara De Servi; TOXICITY POTENTIAL OF EYE DROPS WITH SOFT PRESERVATIVES VERSUS NON-PRESERVED ON HUMAN CORNEAL EPITHELIUM . Invest. Ophthalmol. Vis. Sci. 2017;58(8):2638.
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© ARVO (1962-2015); The Authors (2016-present)
The reconstituted Human Corneal Epithelium (HCE) is a model validated as alternative to animal testing, OECD TG 492. It allows a predictive approach for the assessment of eye irritation and by adopting a multiple endpoints analysis iIt has been able to identify toxicity potential in eye drops and mirrors the chronic toxicity effects observed clinically on the ocular surface. The aim of this study was to assess the eye toxicity potential of soft preservatives (cetrimide, purite, oxyd) in multidose (MD) eye drops versus unpreserved MD and unidose (UD) eye drops.
The EPISKIN HCE of 0.5 cm2 and average 60 mm thickness was used. 30 mL of the following products were applied: Artelac MD, Artelac UD, Optive MD, Optive UD, Artelac Rebalance MD, Artelac Rebalance UD, Thealoz Duo (unpreserved MD) to represent acute exposure (24h followed by 24h post incubation) and repeated exposure (t.i.d for 3 days), in order to investigate the eye irritation potential and cellular damage compared to saline and Benzalkonium Chloride 0.01%, as controls. Outcome measures included the residual cellular viability (MTT), epithelial integrity (TEER measure), cellular membrane integrity (LDH release), occludin (OCLN; functional tight junctions role) level and MMP-9 as extracellular matrix degradation, quantified by qRT-PCR.
The positive control BAK 0.01% significantly reduced cellular viability after both acute (44.81%) and repeated (0.92%) exposures confirming its well-known irritation potential. The MTT, LDH and TEER results after acute exposure suggest absence of direct toxicity and epithelial surface damage from soft preservatives. But after repeated exposure, soft-preserved products results were similar to BAK 0.01%, corresponding to a significant impairment of corneal permeability. This is not the case of preservative-free product in UD or MD vials. Effect on OCLN and MMP-9 genes transcriptional activity was shown with preserved eye drops after acute and repeated exposures.
Even so-called ‘soft’ preservatives cause direct toxicity but also ocular surface impairment. The classification of products according to the level of toxic and disruptive interaction with the corneal epithelium shows that soft preservatives can be as toxic as BAK 0.01% after chronic exposure. Clinicians need to be aware that preserved eye drops should be avoided wherever possible in chronic conditions.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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