Exploration and comparison of in vitro eye irritation tests with the ISO standard in vivo rabbit test for the evaluation of the ocular irritancy of contact lenses.
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.
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Jun-Won
JW
Yun
Department of Microbiology and Immunology, Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Republic of Korea.
Quan
Q
Hailian
Department of Microbiology and Immunology, Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yirang
Y
Na
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Byeong-Cheol
BC
Kang
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Jung-Hee
JH
Yoon
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Eun-Young
EY
Cho
College of Pharmacology, Ewha Womans University, Seoul 120-808, Republic of Korea.
Miri
M
Lee
College of Pharmacology, Ewha Womans University, Seoul 120-808, Republic of Korea.
Da-Eun
DE
Kim
College of Pharmacology, Ewha Womans University, Seoul 120-808, Republic of Korea.
SeungJin
S
Bae
Department of Microbiology and Immunology, Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: lamseok@snu.ac.kr.
Seung Hyeok
SH
Seok
College of Pharmacology, Ewha Womans University, Seoul 120-808, Republic of Korea. Electronic address: kmlim@ewha.ac.kr.
Kyung-Min
KM
Lim
D000826:Animal Testing Alternatives; D000818:Animals; D002417:Cattle; D003261:Contact Lenses / Q000009:adverse effects*; D003318:Corneal Opacity; D004848:Epithelium / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D011817:Rabbits
Animal alternative; BCOP; Contact lens; Eye irritation; ISO10993-10; Medical device; Reconstructed human corneal epithelium, RhCE model