Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model

Abstract

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model.

Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina.

Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation.

Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned.

Translational relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

Figure 1.

External appearance of the previous device design with the solid skirt with partial thickness microperforations (left) versus the revised second-generation prototype with full-thickness macroapertures designed to enhance biointegration (right).

Figure 2.

Light microscopic appearance of the recipient rabbit cornea, with revised second-generation prototype with full-thickness macroapertures in the skirt. Significant fibroblast infiltration and new collagen deposition through the entirety of the full-thickness aperture (red arrow) is evident (Masson's trichrome staining; original magnification ×10).

Figure 3.

Diagram of the second-generation novel synthetic cornea device. The blue color indicates the compact and optically clear material, and the white color indicates the porous ingrowth surface.

Figure 4.

Rabbit 15. Fundus appearance through the novel synthetic cornea device demonstrating a clear view of the optic nerve and retina. The photograph was taken at 12 months postoperatively using the operating microscope (Proveo 8 Ophthalmic Microscope, Leica Microsystems, Wetzlar, Germany) and the BIOM5 HD fundus lens (Oculus Surgical, Inc., Fort Pierce, FL).

Figure 5.

Rabbit 11. Mild focal anterior lamellar thinning at 6 months (red arrow) associated with a tight mattress suture after novel synthetic cornea device implantation in a healthy rabbit eye. The picture on the left depicts the anterior segment's optical coherence appearance. The picture on the right was taken under the operating microscope using external cobalt blue light after topical fluorescein instillation.

Figure 6.

Rabbit 15. Optical coherence tomographic view of a rabbit eye at 12 months demonstrating good apposition of the device within the recipient corneal midstroma and healing response (lighter color) around the optical wall and skirt and through the macroapertures (red arrow). The anterior chamber depth and corneal curvature are unchanged.

Figure 7.

Rabbit 4. Clinical appearance of an area of localized anterior lamellar focal retraction without an infiltrate. This picture was taken under the operating microscope using an external cobalt blue light source and with topical fluorescein drops at day 315.

Figure 8.

Rabbit 8. Clinical appearance of an area of the anterior segment under the operating microscope showing an infiltrate approximately 360° in the recipient cornea overlying the device skirt that preceded endophthalmitis.

Figure 9.

Rabbit 12. Clinical appearance of an area of localized anterior lamellar retraction without an infiltrate. The picture was taken under the operating microscope using an external cobalt blue light source and with topical fluorescein drops.