Abstract
Purpose: To evaluate long-term in vivo functionality of corneas regenerated using a cell-free, liquid hydrogel filler (LiQD Cornea) after deep corneal trauma in the feline model. Methods: Two healthy cats underwent 4 mm diameter stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation. The filler comprising 10% (w/w) collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and 1% fibrinogen and crosslinked with 2% (w/w) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), was applied to the wound bed previously coated with thrombin (250 U/ml). In situ gelation occurred within 5 min, and a temporary tarsorrhaphy was performed. Eyes were examined weekly for 1 month, then monthly over 12 months. Outcome parameters included slit-lamp, Scheimpflug tomography, optical coherence tomography, confocal and specular microscopy, and immunohistochemistry studies. Results: The gelled filler was seamlessly incorporated, supporting smooth corneal re-epithelialization. Progressive in-growth of keratocytes and nerves into the filler corresponding to the mild haze observed faded with time. The regenerated neo-cornea remained stably integrated throughout the 12 months, without swelling, inflammation, infection, neovascularization, or rejection. The surrounding host stroma and endothelium remained normal at all times. Tomography confirmed restoration of a smooth surface curvature. Conclusion: Biointegration of this hydrogel filler allowed stable restoration of corneal shape and transparency in the feline model, with less inflammation and no neovascularization compared to previous reports in the minipig and rabbit models. It offers a promising alternative to cyanoacrylate glue and corneal transplantation for ulcerated and traumatized corneas in human patients.
Highlights
The human cornea is the transparent front of the eye that refracts light into the eye for vision
Non-infectious ulcerative keratitis or perforations were responsible for 16% of the 7,816 stromal or full thickness corneal transplantations performed in the United States in 2019 (EBAA, 2020)
Synthesis of collagen-like peptide conjugated to polyethylene glycol (CLP-polyethylene glycol-based (PEG)), reconstitution of 10% (w/w) CLP-PEG mixed with 1% fibrinogen and crosslinked with 2% (w/w) 4(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), reconstitution of thrombin, mixing and application of the LiQD Cornea were achieved as reported previously (McTiernan et al, 2020)
Summary
The human cornea is the transparent front of the eye that refracts light into the eye for vision. Cyanoacrylate glue is usually used to seal small perforations It is not devoid of complications and it necessitates the use of a therapeutic contact lens to prevent pain, rubbing, or displacement of the glue. Cyanoacrylate glue is not transparent and can block vision if within the visual axis. It can trigger inflammation, scarring and vascularization, and it does not prevent infection. It is a temporary solution requiring more than one application while waiting for a human amniotic membrane patch or a lamellar or full-thickness corneal graft (Vote and Elder, 2000; Anchouche et al, 2020)
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