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Background: Melting corneal ulcers are a serious condition that affects a great number of animals and people around the world and it is characterised by a progressive weakening of the tissue leading to possible severe ophthalmic complications, such as visual impairment or blindness. This disease is routinely treated with medical therapy and keratoplasty, and recently also with alternative regenerative therapies, such as cross-linking, amniotic membrane transplant, and laser. Plasma medicine is another recent example of regenerative treatment that showed promising results in reducing the microbial load of corneal tissue together with maintaining its cellular vitality. Since the effect of helium plasma application on corneal mechanical viscoelasticity has not yet been investigated, the aim of this study is first to evaluate it on ex vivo porcine corneas for different exposition times and then to compare the results with previous data on cross-linking treatment., Results: 94 ex vivo porcine corneas divided into 16 populations (healthy or injured, fresh or cultured and treated or not with plasma or cross-linking) were analysed. For each population, a biomechanical analysis was performed by uniaxial stress-relaxation tests, and a statistical analysis was carried out considering the characteristic mechanical parameters. In terms of equilibrium normalised stress, no statistically significant difference resulted when the healthy corneas were compared with lesioned plasma-treated ones, independently of treatment time, contrary to what was obtained about the cross-linking treated corneas which exhibited more intense relaxation phenomena., Conclusions: In this study, the influence of the Helium plasma treatment was observed on the viscoelasticity of porcine corneas ex vivo, by restoring in lesioned tissue a degree of relaxation similar to the one of the native tissue, even after only 2 min of application. Therefore, the obtained results suggest that plasma treatment is a promising new regenerative ophthalmic therapy for melting corneal ulcers, laying the groundwork for further studies to correlate the mechanical findings with corneal histology and ultrastructural anatomy after plasma treatment., (© 2024. The Author(s).)