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Development of an Artificial Cornea for the Human Eye

Final Report Summary - CORNEA (Development of an Artificial Cornea for the Human Eye)

The cornea is the entrance window of the eye. It shields the eye from dust and germs, and at the same time acts as the eye's outermost lens contributing about 75 % of the eye's focusing power. Opacification of the cornea of the human eye results in the loss of vision and finally blindness unless corrected by a corneal transplant. More than 40 000 keratoplasties per year are performed in Europe and the United States each, with a continuous increase in recent years, and with success rates from more than 90 % to less than 50 %. Low success rates are associated with dry eyes, Herpes keratitis, corneal vascularisation, recurring uveitis, acid burns, and traumatic anatomic structures of the anterior eye. The lack of donor corneas resulted in long waiting lists of patients in developed countries, and their non-availability in developing countries in millions of treatable blind people. There is a long history of attempts to replace the human cornea by alloplastic material with either disappointing results, or complicated multiple surgeries associated with severe drawbacks for the patient. The CORNEA project combines several cutting-edge technologies in order to achieve a never before available implant design and precision of surgery, and open the chance to regain vision for otherwise blind people. The artificial cornea developed in our project required three chemically or physically different surfaces in order to meet the desired properties. The skirt was to be of such a nature, that fibrin and tissue will stick on it, thus providing a good base for cell growth and healing. The optical part of the artificial cornea had to display two different surfaces. The 'inner' side (which is directed to the eye) of the artificial cornea should be coated with such a material, preventing the adsorption of proteins and cell growing, thus guaranteeing that the optical part stays clear. The 'outer' side of the artificial cornea was to be hydrophilic to provide a smooth surface and wet-ability by the tear film. The approach, to achieve these requirements was the coating with appropriate chemicals.

Keratoprostheses usually consist of a cylindrically shaped optical part and a surrounding skirt (called haptic) which ensures tight connection to the ocular tissue of the patient. The CORNEA keratoprosthesis should preferably be manufactured by mechanical shaping from one piece of polymer for long-term tight connection between the optic and haptic parts. The polymer should be hydrophobic (i.e. absorb less than 2 % water) in order to avoid interaction with eye medications and dimensional changes due to changes in hydration. Moreover, the polymer should be flexible in order to allow the haptic to follow the movement of the surrounding corneal tissue and prevent local stress. Last not least, the polymer must be optically clear and should be from a group of polymers with a history of safe use in human eyes. Therefore, the consortium focused on the evaluation of various acrylic polymers with a glass transition temperature around 10 degrees Celsius. This allows mechanical shaping at low temperature and flexibility at the temperature of the human eye. A number of different polymers was preselected and tested for coat-ability. The physico-chemical and biological properties of coated platelets were systematically investigated.

The processes of cryo-lathing and cryo-milling of flexible, hydrophobic acrylic polymers was developed in order to manufacture keratoprostheses of various geometry for testing and later for adjustment to patients' individual needs.

The consortium tried various processes of polymer surface activation as the first step in firmly coating the polymers. Plasma activation proved to be the most effective one on the polymers under consideration. Subsequently the consortium developed three different coating processes: multilayer coating with Fibronectin to ensure tissue growth on the keratoprosthesis haptic; multilayer coating with Heparin Sodium on the 'inner' surface of the keratoprosthesis optic to prevent membrane formation on the surface of the implant; strongly hydrophilic coating by forming an interpenetrating polymer network on the 'outer' surface of the keratoprosthesis optic.

Surgical implants need to be supplied sterile, i.e. free from viable microorganisms. Therefore, they need to undergo a sterilisation process. During the CORNEA project it turned out that the standard sterilisation processes used in the manufacture of ophthalmic implants such as intraocular lenses (steam sterilisation or gas sterilisation) will destroy the biochemical properties of the coated polymer surfaces: cells will no more adhere to the Fibrin coating after sterilisation. Therefore, the consortium developed a sterilisation process where the keratoprostheses are cooled to – 78.5 degrees Celsius while being treated with gamma irradiation. This process was tested for both its influence on the bulk polymer as well as on the coatings, and validated with respect to microbiological effectiveness.

The CORNEA consortium organised a symposium with experts in cornea surgery in December 2005 and established a medical advisory board. In addition to the five consortium partners with clinical experience the medical advisory board assisted the CORNEA consortium in the decision making process of keratoprosthesis design and surgical techniques.

Based on the results of performance testing in animal eyes the geometric design of the keratoprosthesis finally to be implanted in human eyes was optimised. The final CORNEA keratoprosthesis design was tested for optical performance in a set-up intended for the measurement of intraocular lenses but modified for the specific situation of keratoprostheses having the 'outer' optic against air. As expected the optical performance is good for light rays along the optical axis, however, has design related compromises for light rays with an angle to the optical axis.

The polymer of the keratoprosthesis was tested for hydrolytic stability, photostability, and stability against exposure to Nd:YAG laser shots and proven sufficiently stable; the picture on the right shows a scanning electron micrograph of the polymer surface after Nd:YAG laser exposure.

Based on literature and preclinical test results a clinical evaluation in accordance with the European Medical Devices Directive 93/42/EEC was performed, concluding that the CORNEA keratoprosthesis has a similar risk profile to other comparable keratoprostheses on the market, and that the potential benefit to the physician and patients outweigh the potential risks by far. The overall residual design risks, manufacturing risks, and the risk / benefit ratio of the devices when used on patients according to the manufacturer's instructions for use are fully acceptable.

The keratoprosthesis developed within the EU-funded CORNEA project will be made available under the tradename 'Miro Cornea Ur'. The implant will first be used on five patients' eyes, and after successful close follow-up of these initial patients on further 35 patients' eyes, before it will be made available to a larger number of specialised ophthalmic surgical centres. The first 40 patients will be selected and monitored under a 'post-marketing clinical follow-up plan' and patients' informed consent obtained. This study has been submitted for approval to the Ethics Committee of Martin-Luther-Universität Halle- Wittenberg, Medical Faculty, and been approved under conditions on 18 June 2008. The expected impact will be an artificial substitute for the human cornea for treating blind people or such with a damaged cornea.

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