Drug-dependent inhibitory effects on corneal epithelium structure, cell viability, and corneal wound healing by local anesthetics

Abstract

Local anesthetics are commonly used in ophthalmic surgery. However, their use can affect the healing process. This study aimed to investigate the potential impact of anesthetic substances at clinically relevant concentrations and incubation times (3 min), specifically oxybuprocaine (OBPC, 0.4%), lidocaine (LIDO, 2%), and bupivacaine (BUPI, 0.5%), either alone or supplemented with hylase (HYLA, 30 I.E.), on corneal epithelium structure, cell viability, and wound healing. To assess the potential cytotoxicity of these anesthetic substances, viability and colony-forming efficiency (CFE) assays were conducted using the human telomerase-immortalized corneal epithelial (hTCEpi) cell line. Additionally, the toxicity of these substances was evaluated using a 3D human tissue-specific corneal epithelial construct as well as a porcine corneal culture model. The results indicate that OBPC (Novesine® 0.4%) exhibited significant cytotoxicity in 2D and 3D corneal epithelial cell culture models and delayed wound healing in the ex vivo porcine corneal organ culture model. In contrast, LIDO, BUPI, and HYLA were less cytotoxic to corneal cells, with no observed impact on wound healing in the porcine corneal organ culture model. In summary, local anesthetics commonly used in eye surgery are generally considered safe. However, the application of OBPC (Novesine® 0.4%) may delay wound healing.