A Better Artificial Cornea

Novel keratoprosthesis designed for optimal integration with host issue. Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA The first two patients implanted with a completely synthetic keratoprosthesis (CorNeat KPro, CorNeat Vision) are doing well during follow-up ranging from three to seven months, reported Gilad Litvin MD at the Innovators general session. His key message, however, was the preclinical and early clinical experience with the device shows the ability to achieve seamless integration of artificial material with resident human tissue. “I think the technology ushers in the way to a new era of medical devices,” said Dr Litvin, inventor of the keratoprosthesis. KERATOPROSTHESIS DESIGN The novel device has two elements—a central PMMA optic and a surrounding synthetic nanofabric integrating skirt. Unlike existing keratoprostheses that integrate with corneal tissue, the CorNeat KPro anchors in the subconjunctival space, and its integrating skirt provides a scaffold onto which fibroblasts from Tenon’s capsule can migrate. “Whereas the cornea is devoid of blood vessels and lacks a significant cellular component, the subconjunctival space is a vascularised site that heals vigorously,” Dr Litvin explained. The skirt’s nanofabric material is manufactured by a chemical engineering process called electrospinning. This process can create a nonwoven matrix in the nanometre and micrometre scale. It fuses to the optical element of the keratoprosthesis at the rim of the PMMA lens, an area designed with features facilitating implantation, future surgery, device integration, and retention. The rim contains three pairs of suturing holes for passing nondegradable sutures that anchor the device to the eye wall. In addition, it has four ports that allow future access into the ante-rior or posterior chamber. The rim also has grooves filled with the nanofabric that promotes tissue invasion, helping to secure the PMMA optic to the eye. The optical element has a posterior undercut that houses the remnant cornea while ensuring centralisation of the device and a watertight seal. Flanges in the undercut help the surgeon with inserting the cornea and then securing it. PRECLINICAL AND FIRST IN-HUMAN EXPERIENCE Rabbit studies helped establish surgical feasibility and biocompatibility. “Histological evaluations show the presence of abundant cell nuclei interspersed between the fibrils of the nanofabric skirt, collagen, and even capillaries coursing their way from one end of the skirt to the other,” Dr Litvin stated. Irit Bahar MD, Rabin Medical Center, Petah Tikva, Israel, performed the first in-human implantation of the novel keratoprosthesis in January 2021. The surgery begins with a 360-degree peritomy followed by epithelial debridement to avoid downgrowth. Then the centre of the cornea is stamped with a specially developed marker tool. The markings identify the locations of the access ports, suturing positions, and the trephination’s edge, thus assisting the surgeon in locating the paracenteses and visualising the trephination’s edge, Dr Litvin explained. After filling the eye with viscoelastic, the surgeon places three non-degradable sutures, first through the device and then through the corneosclera. Trephination follows, and then the surgeon pulls on the distal ends of the corneal sutures to approximate the device to the eye wall. “This seals the eye and stops the open sky segment of the procedure,” Dr Litvin said. The trephined corneal edge is inserted into the posterior undercut of the optical element using another specialised tool known as the Snapper. Finally, the conjunctiva is repositioned, sutured over the integrating skirt with biodegradable sutures, and sealed with fibrin tissue glue. The first recipient of the synthetic keratoprosthesis had one functioning eye that had undergone four corneal transplantation procedures. After the fourth procedure, which was performed about 10 years earlier, he developed an Acanthamoeba infection that left the transplant completely opaque. “The patient has optic nerve damage, but at seven months after implantation, he is seeing 6/90 (~20/320) and is very pleased,” Dr Litvin said. The second patient had a history of ocular cicatricial pemphigoid and had not been able to see for 30 years. At three months following keratoprosthesis implantation, his visual acuity was 6/9 (~20/30). Some conjunctival retraction was observed during the first few weeks postoperatively in both patients. However, it stabilised after the tissue adhered to the skirt material, and the retraction has not been associated with any untoward sequelae. “In the rabbits, histology revealed that the skirt was filled with collagen, fibroblasts, and even capillaries. This was also evident in the areas where there was conjunctival retraction, blocking any access into the anterior chamber,” Dr Litvin said. “In the first patient, conjunctival retraction has left approximately 1.5 mm of the device rim without conjunctival covering, but the patient is not bothered by it, and his anterior chamber remains quiet.” Currently, IOP monitoring occurs through digital palpation. Patients are also being followed for glaucomatous damage with serial optical coherence tomography imaging of the retinal nerve fibre layer and visual field testing, which is possible because the PMMA lens has a large, 6.5 mm optical zone. Work is underway to develop a second generation of the keratoprosthesis that will have an embedded IOP sensor. Gilad Litvin MD is the Co-Founder, Chairman, and Chief Medical Officer of CorNeat Vision, Ra’anana, Israel. gilad@corneat.com

Tags: cornea