Development of Sensitive In Vitro Protocols for the Biocompatibility Testing of Medical Devices and Pharmaceuticals Intended for Contact with the Eyes: Acute Irritation and Phototoxicity Assessment

This study introduces a novel in vitro methodology that employs the 3-D reconstructed tissue model, EpiOcular, to assess the irritation and phototoxicity potential of medical devices and drugs in contact with the eye. Our study evaluated diverse test materials, including medical devices, ophthalmological solutions and an experimental drug (cemtirestat), for their potential to cause eye irritation and phototoxicity. The protocols used in this study with the EpiOcular tissue model were akin to those used in the ultra-mildness testing of cosmetic formulations, which is challenging to predict with standard in vivo rabbit tests. To design these protocols, we leveraged experience gained from the validation project on the EpiDerm skin irritation test for medical devices (ISO 10993-23:2021) and the OECD TG 498 method for photo-irritation testing. The predictions were based on the tissue viability and inflammatory response, as determined by IL-1α release. By developing and evaluating these protocols for medical devices, we aimed to expand the applicability domain of the tests referred to in ISO 10993-23. This will contribute to the standardization and cost-effective safety evaluation of ophthalmic products, while reducing reliance on animal testing in this field. The findings obtained from the EpiOcular model in the photo-irritation test could support its implementation in the testing strategies outlined in OECD TG 498

EpiOcular, OCL-200, eye irritation, ocular irritation, phototoxicity, medical devices extracts, IL-1a,  UVA, solar light, drugs, ophthalmic solutions, Bio-spun Polyethylene terephthalate (PET),  Polycaprolactone (PCL) microfibres, PDMS loaded with quantum dots, hypromellose, boric acid, sodium tetraborate decahydrate, Euphrasia rostkoviana extract, phosphatidylcholine, phosphatidylethanolamine, sodium chloride, zinc sulphate heptahydrate, alpha-tocopheryl acetate, caprylic/capric triglyceride, polysorbate 80, disodium edetate dihydrate, sodium hydroxide, hyaluronic acid,  potassium chloride, sodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate, Hydranate, boric acid, edetate disodium, poloxamine, sodium borate, Intra-ocular lenses, acrylate methacrylate copolymer, benzalkonium chloride, disodium edetate dihydrate, magnesium chloride hexahydrate, aldose reductase inhibitor, chlorpromazine hydrochloride, sesame seed oil, Occusept, Hyal-Drop, ReNu Multi Plus, Ophthalmo-Septonex, OCUflash, blue

Bio-spun Polyethylene terephthalate (PET),  Polycaprolactone (PCL) microfibres, PDMS loaded with quantum dots, hypromellose, boric acid, sodium tetraborate decahydrate, Euphrasia rostkoviana extract, phosphatidylcholine, phosphatidylethanolamine, sodium chloride, zinc sulphate heptahydrate, alpha-tocopheryl acetate, caprylic/capric triglyceride, polysorbate 80, disodium edetate dihydrate, sodium hydroxide, hyaluronic acid,  potassium chloride, sodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate, Hydranate, boric acid, edetate disodium, poloxamine, sodium borate, Intra-ocular lenses, acrylate methacrylate copolymer, benzalkonium chloride, disodium edetate dihydrate, magnesium chloride hexahydrate, aldose reductase inhibitor, chlorpromazine hydrochloride, sesame seed oil, Occusept, Hyal-Drop, ReNu Multi Plus, Ophthalmo-Septonex, OCUflash, blue