In an effort to explore the use of alternative methods to animal testing for the evaluation of the ocular irritancy of medical devices, we evaluated representative contact lenses with the bovine corneal opacity and permeability test (BCOP) and an in vitro eye irritation test using the three-dimensionally-reconstructed human corneal epithelium (RhCE) models, EpiOcular™ and MCTT HCE™. In addition, we compared the obtained results with the ISO standard in vivo rabbit eye irritation test (ISO10993-10). Along with the positive controls (benzalkonium chloride, BAK, 0.02, 0.2, and 1%), the extracts of 4 representative contact lenses (soft, disposable, hard, and colored lenses) and 2 reference lenses (dye-eluting and BAK-coated lenses) were tested. All the lenses, except for the BAK-coated lens, were determined non-irritants in all test methods, while the positive controls yielded relevant results. More importantly, BCOP, EpiOcular™, and MCTT HCE™ yielded a consistent decision for all the tested samples, with the exception of 0.2% BAK in BCOP, for which no prediction could be made. Overall, all the in vitro tests correlated well with the in vivo rabbit eye irritation test, and furthermore, the combination of in vitro tests as a tiered testing strategy was able to produce results similar to those seen in vivo. These observations suggest that such methods can be used as alternative assays to replace the conventional in vivo test method in the evaluation of the ocular irritancy of ophthalmic medical devices, although further study is necessary.
Bibliographical noteFunding Information:
We thank ICK ContactLens and Sunkyung RGP for kindly providing results of the in vivo eye irritation tests conducted by the Korean Testing and Research Institute. We also thank the managing director, Noh-Jin Park of Hyupsin Food Co. Ltd. for kindly providing the fresh bovine eyes. This research was supported by a grant ( 15182MFDS461 ) from the Ministry of Food and Drug Safety and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. HI13C1046 ).
- Animal alternative
- Contact lens
- Eye irritation
- Medical device
- Reconstructed human corneal epithelium, RhCE model