Results of a Phase I-IIA Multicentre Clinical Trial Evaluating an Allogeneic Nanostructured Artificial Anterior Human Cornea.

Abstract

Purpose : There is a need to find alternatives to donor corneas because of their limited availability to perform corneal transplants. To address this issue, we have developed a nanostructured fibrin-agarose anterior corneal substitute combining allogeneic corneal cells, which is under clinical evaluation in a phase IIA multicentre clinical trial.

Methods : We enrolled 5 patients suffering from severe corneal ulcer, or its sequelae (mainly severe fibrosis), persistent to conventional treatments. All of them were grafted with an anterior lamellar corneal substitute based on a fibrin-agarose scaffold containing allogeneic keratocytes and corneal epithelial cells. Different variables were evaluated during a 2-year-follow-up: existence of serious adverse events (SAE), corneal integrity, infection, neovascularization (NV), corneal healing and visual acuity (VA). The ocular complication scores were obtained by the Sotozono's and SICCA OSS scales. Anterior segment optical coherence tomography and confocal microscopy were performed. Moreover, improvement of patient's quality of life was evaluated with a validated questionnaire.

Results : All patients had a complete healing of the corneal lesion with no SAE treatment-related. No surgical complications were observed. In all cases, there was good integration of the transplanted tissue with no signs of rejection or infection during the follow-up. VA improved in 3 cases. NV did not increase in any of the patients. Moreover, a significant decrease in the Sotozono's (-6,7±1,14; p<0.05) and SICCA OSS (–5,8 ±1,16; p<0.05) scales after the intervention was observed, comparing preoperative vs 2-year-postoperative status. Confocal microscopy showed a metaplastic epithelium in all cases. Furthermore, all patients referred a significant improvement in their ocular symptoms.

Conclusions : These results suggest that fibrin-agarose-based corneal substitute is a safe treatment in severe trophic corneal ulcer or its sequelae, which might facilitate the regeneration of the corneal surface. Clinical improvement was observed in all patients based on an increase in visual acuity and/or an improvement in ocular symptoms. This research was funded by the Carlos III Health Institute, Ministry of Economy and Competitiveness, (co-funded by FEDER funds, EU). Project FIS PI14 / 0955.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.