Cell-free liquid hydrogel sealant/filler restores long term corneal integrity and shape after perforating and non-perforating trauma in feline eyes

Abstract

Purpose : To evaluate long term in vivo functionality of corneas regenerated using a cell-free, liquid hydrogel sealant/filler (LiQD Cornea; McTiernan et al., Sci. Adv. 2020) following deep corneal ablation with or without perforation in the feline model.

Methods : Two healthy cats underwent 3 and 1,5 mm diameter x stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation of the wound bed. The filler, made of 10% (w/w) CLP-PEG mixed with 1% fibrinogen and crosslinked with 2% (w/w) DMTMM, was applied to the wound bed that had been pre-coated with thrombin (250 U/ml). In situ gelation occurred within 5 min and a temporary tarsorrhaphy was performed. Examinations were performed weekly for 1 month and then monthly for 12 months. In vivo Outcome parameters included: slit-lamp assessment, Scheimpflug tomography, optical coherence tomography (OCT), confocal microscopy (CM), and endothelial cell morphometry, and ex vivo: transmission electron microscopy (TEM) and immunohistochemistry, including study of extracellular vesicles and exosomes.

Results : A smooth epithelial layer re-grew over the filled defects. The gelled filler remained stably integrated through the entire 12 months, without swelling, neovascularization, inflammation, infection, or rejection. Slit lamp, OCT (Fig.1), and CM showed progressive replacement of the filler by a more reflective tissue smoothly filling the wound bed, while keratocytes and nerves began to be seen, suggesting remodeling of the gel. The mild haze, maximum at 2-3 months, seen at the wound interface and within the remodeling tissue, disappeared with time. Host stroma and endothelium remained normal at all times. Tomography confirmed restoration of smooth and normal corneal surface curvature (Fig.2).

Conclusions : Biointegration of this hydrogel filler allowed stable restoration of normal 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.

This is a 2021 ARVO Annual Meeting abstract.

 

OCT: Postop remodeling of the filler.

 

Tomography: Postop rehabilitation of a normal front surface sagittal curvature