INTRODUCTION: Corneal damage can happen due to a variety of insults, including environmental factors and iatrogenic issues. For instance, the corneal epithelium is sensitive to oxidative stress caused by reactive oxygen species (ROS) or by ultraviolet B (UVB) radiation. Moreover, the strictly correlated oxidative damage and inflammatory processes impair the corneal reparative wound healing mechanism. Corneal protection after damage remains an unmet medical need that requires urgent management. Sodium hyaluronate is known to protect the cornea against oxidative and inflammatory injury. Additionally, vitamin B12 is a good candidate for counteracting corneal damage, helping preserve visual functions. METHODS: The present study aimed to investigate the potential protective effect of an ophthalmic formulation based on 0.01% vitamin B12% and 0.15% sodium hyaluronate (DROPYAL EVO) compared to other ophthalmic formulations containing sodium hyaluronate and trehalose (TRIMIX and THEALOZ DUO). Two different RESULTS: The eye drops containing vitamin B12 were able to significantly counteract oxidative and inflammatory damage in corneal epithelial cells exposed to H DISCUSSION: Vitamin B12 potentially enhances the protective effect of sodium hyaluronate, accelerating the wound healing process and modulating oxidative stress and inflammation. Vitamin B12, in combination with sodium hyaluronate, could represent a promising approach to managing corneal epithelial damage. Further clinical investigations are needed to confirm this data.