Topical treatment with a new matrix therapy agent or regenerating agent (RGTA) (CACICOL) improves epithelial wound healing after penetrating keratoplasty in a rabbit model

Abstract

Purpose: Complete epithelial wound healing is a milestone in the early post-operative care after penetrating keratoplasty (PKP). It reduces the infectious risk, allows safe instillation of steroids, and conditions discharge from hospitalization. The present study assessed a new matrix therapy agent, mimicking heparan sulfates, for the management of post PKP epithelial defects in a preclinical model of PKP in rabbits.

Methods: New Zealand white rabbits received a 7.25/7mm PKP (one eye) with a desepithelialized rabbit cornea from the same sibling. The allografts were sutured with a 16 passages running suture with a 10.0 nylon and buried notch. Immunosuppression was obtained thanks to subconjonctival corticosteroid to avoid eyedrops. Rabbits were randomized to receive either CACICOL (n=3) or vehicle (n=3). Investigators were masked to the treatment. Eyedrops were instilled immediately after graft and repeated on alternate day until complete reepithelilalization. The epithelial wound healing was monitored using standardized slit lamp imaging after fluorescein staining, repeated each two days under general anaesthesia. Corneal thickness was monitored using AS-OCT (Casia SS-1000, Tomey). Rabbits were euthanatized and corneas were analyzed using conventional histological cross sections, confocal microscopy (Fluoview 1200, Olympus) after Dioc6 staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Results: Corneas receiving CACICOL healed in 6, 6 and 8 days versus 8, 8 and 10 days with the placebo (P=0,099). Graft thicknesses did not differ. Epithelial thicknesses (by confocal microscopy) were 45, 32 et 23 µm with CACICOL and 25, 29 et 19 µm with the vehicle. In SEM superficial cells of the CACICOL group were similar to normal corneas and had more numerous microvilli with the placebo. MET showed that the epithelial ultrastructure of the CACICOL group was similar to the normal cornea with cuboid basal cells containing numerous hemidesmosomes whereas the vehicle group, basal cells were not cuboid, had less numerous anchoring complexes and less cell layers.

Conclusions: CACICOL seems a potentially useful, noninvasive therapeutic approach in PKP management. A controlled double blind clinical trial vs placebo will be soon conducted to answer this question conclusively.