WO2008055118A2 - Methods and systems for immobilizing corneal prostheses - Google Patents

Abstract

Corneal prostheses, such as onlays and implants, have a surface which displays a native biomolecule capable of cross-linking with endogenous moieties in corneal tissue. After placement, such prostheses may be immobilized by exposure to ultraviolet or other irradiation which cross-links the biomolecules with the endogenous moieties.

Description

METHODS AND SYSTEMS FOR IMMOBILIZING CORNEAL PROSTHESES

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention. Corneal onlays are corneal prostheses placed on

Bowman's membrane. Corneal implants are corneal prostheses which are placed within the corneal stroma e.g. below the level of Bowman's membrane. A significant problem with existing designs for corneal onlays and corneal implants is that there currently are not any good methods to attach these prostheses to the cornea.

[0002] Existing methods for attachment of corneal prostheses include sutures and adhesives. Sutures are unsatisfactory because they may cause damage to the prosthesis and distort the shape of the prosthesis. Any distortion of the prosthesis may result in degradation of its optical properties. Sutures also take considerable time and skill to place. Adhesives e.g. glues are also unsatisfactory because they are difficult to apply to the cornea in an even and smooth fashion. Adhesives tend to flow irregularly, and the volume of adhesive applied is difficult to control at the microscopic level. Lack of evenness or smoothness underneath or around the corneal prosthesis may distort the shape of the prosthesis and degrade its optical properties. For example, it is known that a 10 micron (0.01 mm) change in the contour of a prosthesis may cause an unacceptable 1 diopter change in the optical power of the prosthesis. It is also important to note that using current techniques it is not possible to control the thickness or evenness of adhesives to even the 10 micron level.

[0003] For the above reasons, it would be useful to have improved corneal prostheses and methods which allow attachment of the corneal prosthesis to the cornea without the use of sutures or adhesives.

[0004] 2. Description of the Background Art. Leukel et al in U.S. Patent 6,555,103 describes ophthalmic and other biomedical moldings which have been modified to display particular synthetic surface free radicals Such biomedical moldings can be attached to corneal tissue by irradiation, particularly irradiation by ultraviolet light. The use of such synthetic attachment radicals suffers from potential toxicity and cell growth inhibition. In U.S. Patent 6,555,103, an experiment is conducted which shows that a polymer can be attached to the cornea of a cat by Leukel's method. In this same experiment, it was shown that corneal epithelium was unable to grow over the surface of the polymer even after several days except at the periphery. The inability of the epithelial cells to grow over the polymer may be due, at least in part, to the presence of the synthetic free radicals. There is therefore still a need for improved corneal prostheses and methods of attachment.

SUMMARY OF THE INVENTION

[0005] The present invention provides improved corneal prostheses and methods for immobilizing such prostheses on a cornea. The prostheses may be any type of prosthesis, such as an onlay or an implant, having a polymeric body with corrective optical properties or cosmetic properties. The present invention relies on modifying at least one of a posterior surface and/or an anterior surface of the prosthesis. The posterior surface may be modified to promote covalent attachment to the corneal tissue. The anterior surface may be modified to promote epathelialization. The surface modifications will have little or no effect on the corrective optical properties of the prosthesis either before or after implantation.

[0006] In a first aspect of the present invention, a method for immobilizing a corneal prosthesis on a cornea comprises positioning the corneal prosthesis in contact with corneal tissue. At least a portion of an interior surface of the prosthesis displays a "native" cross- linking biomolecule such that, by irradiating the corneal prosthesis with energy under conditions selected to cross-link the native biomolecule with endogenous moieties in the corneal tissue, the prosthesis is immobilized on the tissue. Both the concentration of cross- linking molecule introduced and the conditions of irradiation are selected so that the prosthesis will remain in place without significant displacement during all normal patient conditions and activities. The bonding, however, will not be so strong that the prosthesis cannot be removed by peeling or other intentional removal step.

[0007] The prosthesis body will typically be composed of an optical polymer, which at least partially contains one or more compounds selected from the group consisting of collagen, polyurethanes, poly(2-hydroxyethylmethacrylate), polyvinylpyrolidone, polyglycerolmethacrylate, polyvinyl alcohol, polyethylene glycol, polymethacrylic acid, silicones, polyfluorocarbons, N-isopropylacrylamide, l-ethyl-3,3' (dimethyl- aminopropyl)carbodidimide, N-hydroxysuccinimidepolymers with phosphocholine [0008] Another group of polymers which may be appropriate for the manufacture of the prosthesis body consists of polysiloxanes, perfluoroalkyl polyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl (meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, polyolefines, or fluorinated polyolefines, such as polyvinylidene fluoride, fluorinated ethylene propylene, or tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-l ,3-dioxol. Examples of suitable bulk materials are e.g. Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon, Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon or Teflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which are copolymers of about 63 to 73 mol % of perfluoro-2,2-dimethyl-l ,3-dioxol and about 37 to 27 mol % of tetrafluoroethylene, or of about 80 to 90 mol % of perfluoro-2,2-dimethyl-l ,3-dioxol and about 20 to 10 mol % of tetrafluoroethylene. A group of particularly preferred hydrophobic polymers are non-porous or particularly porous perfluoroalkyl polyether (PFPE) homo- or copolymers or perfluoroalkyl acrylates or methacrylates, for example those as disclosed in PCT applications WO 96/31546, WO 96/31548, WO 97/35906 or WO 00/15686.

[0009] Another preferred group of polymers suitable for manufacture of the prosthesis body consists of those being conventionally used for the manufacture of biomedical devices, e.g. contact lenses, which are hydrophilic per se, since hydrophilic groups, e.g. carboxy, carbamoyl, sulfate, sulfonate, phosphate, amine, ammonium or hydroxy groups, are inherently present in the material. Such materials are known to the skilled artisan and comprise for example polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate (HEMA), polyvinyl pyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, poly- N,N-dimethyl acrylamide (DMA), polyvinyl alcohol, copolymers for example from two or more monomers from the group hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid, acrylamide, N,N-dimethyl acrylamide, vinyl alcohol, vinyl acetate and the like, polyalkylene glycols such as polyethylene glycols, polypropylene glycols or polyethylene/polypropylene glycol block copolymers. Typical examples are e.g. Polymacon, Tefilcon, Methafϊlcon, Deltafilcon, Bufϊlcon, Phemfϊlcon, Ocufϊlcon, Focofilcon, Etafilcon, Hefilcon, Vifilcon, Tetrafilcon, Perfilcon, Droxifilcon, Dimefilcon, Isofilcon, Mafilcon, Nelfϊlcon or Atlafilcon.

[0010] Another group of preferred polymers for the prosthesis body consists of amphiphilic segmented copolymers comprising at least one hydrophobic segment and at least one hydrophilic segment which are linked through a direct bond or a bridge member. Examples are silicone hydrogels, for example those disclosed in PCT applications WO 96/31792 and WO 97/49740.

[0011] The native cross-linking biomolecule will usually comprise a human protein or polypeptide but could also include other biomolecules such as carbohydrates and small molecules. Exemplary cross-linking biomolecules include proteins selected from the group consisting of collagen, fibronectin, laminin, kalinin, K-laminin, vitronectin, talin, integrin, albumin, insulin-like growth factor, fibroblast growth factor, hepatocyte growth factor, epithelial growth factor, transforming growth factor-α., transforming growth factor-β, keratinocyte growth factor, heparin binding factor, fibroblast growth factor, nerve growth factor, substance P, interleukin-1 α, and interleukin-1 β, polypeptides selected from the group consisting of FAP, YIGSR, SIYITRF, PHSRN, IAFQRN, and LQVQLSIR; and small molecules selected from the group consisting of 1 ,8 naphthalimide, diazopyruvate, diazopyruvamides , or the like.

[0012] In the case of diazopyruvate or a diazopyruvamide as the cross-linking biomolecule, in preferred aspects the general formula is RHNCOCOCHN2 where R is a tethering molecule selected from the group consisting of oligopeptides, polypeptides, and polyethylene glycol. In additional preferred aspects the diazopyruvate is 4-nitrophenyl-3 -diazopyruvate.

[0013] The irradiation step may optionally be performed in the presence of a non-toxic catalyst which is selected to promote cross-linking, such as riboflavin, rose Bengal or glucose. Optionally, at least a portion of the posterior side of the prosthesis may display a tissue growth promotant in order to promote tissue growth adjacent to the prosthesis after placement and implantation.

[0014] In a separate aspect of the present invention, corneal prostheses comprise a polymeric body having corrective optical properties. At least a portion of an anterior surface of the optical body displays native biomolecules, as described above, which cross-link with endogenous corneal moieties in the corneal tissue when exposed to ultraviolet or other selected radiation. The prosthesis will typically be an onlay or an implant, and the prosthesis body will be typically at least partially contains one or more compounds selected from the group consisting of collagen, polyurethanes, poly(2-hydroxyethylmethacrylate), polyvinylpyrolidone, polyglycerolmethacrylate, polyvinyl alcohol, polyethylene glycol, polymethacrylic acid, silicones, polyfluorocarbons,N-isopropylacrylamide, l-ethyl-3,3' (dimethyl-aminopropyl)carbodidimide, N-hydroxysuccinimide and polymers with phosphocholine.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 schematically illustrates attachment of a prosthesis to a cornea in accordance with the principles of the present invention.

[0016] Figure 2 illustrates a bonding reaction between a PHEMA/MAA prosthesis derivatized with diazopyruvamide and corneal collagen.

[0017] Figures 3A and 3B illustrate an apparatus suitable for performing the methods of Figure 1.

[0018] Figure 4 is a schematic illustration of a corneal prosthesis intended for treating presbyopia.

DETAILED DESCRIPTION OF THE INVENTION

[0019] Corneal prostheses (e.g. implants or onlays) are modified to contain naturally occurring non-toxic proteins, peptides, amino acids or amino acid derivatives or other small molecules capable of becoming chemically bonded to endogenous molecules in the cornea through exposure to irradiation. The resulting chemical bonds will be sufficiently strong to immobilize the prosthesis, that is hold the prosthesis in place, on the cornea under normal patient conditions and activities but may be broken by either physical force or by exposure to solvents to allow removal of the corneal prosthesis in the event that the corneal prosthesis needs to be removed.

[0020] In preferred aspects, the corneal prosthesis is surface modified (attached) with a native biomolecule or derivative thereof, usually mammalian, most usually human extracellular matrix proteins e.g. collagen, fibronectin, laminin, peptide fragments of extracellular matrix proteins e.g. fibronectin adhesion-promoting peptide sequence (FAP), or a diazopyruvate (e.g. 4-nitrophenyl-3-diazopyruvate). Such proteins and derivatives may be purified from human and other sources but will more usually be recombinantly produced. Surface modification (attachment of the proteins to the prosthesis surface) can be achieved by the methods described in Jacob et al (U.S. Patent application 2002/0007217) and Myung et al (U.S. Patent application 2006/0083773), the full disclosures of which are incorporated herein by reference, but other methods of surface modification may also be used. In preferred aspects, the native biomolecule is attached to the corneal prosthesis by a nontoxic spacer molecule (e.g. polyethylene glycol, an olgiopeptide or a polypeptide). In alternate preferred aspects, the corneal prosthesis may be formed from a polymer which contains native biomolecules within the polymer e.g. collagen, fibronectin, laminin, peptide fragments of extracellular matrix proteins, a diazopyruvate or a diazopyruvamide.

[0021] Fixation of a corneal onlay on the cornea according to the present invention may be initiated, for example, by irradiation, particularly by irradiation with ultraviolet or visible light. Preferably, the cornea is previously prepared for the attachment of the onlay, for example by removing the epithelial cell layers of the cornea by scraping. In general, the onlay is placed in intimate contact with the corneal tissue and is then irradiated. Suitable light sources for the irradiation are known to the artisan and comprise for example mercury lamps, high pressure mercury lamps, xenon lamps, carbon arc lamps or sunlight. Sensitizers may be used to shift the irradiation wavelength. In addition, a suitable filter may be used to limit the irradiation to a specific wavelength range. Preferably, the onlay surface to which have been previously applied the native biomolecules is irradiated with light of a wavelength 300 nm, preferably from 350 to 400 nm. The time period of irradiation is not critical but is usually in the range of up to 30 minutes, preferably from 10 seconds to 10 minutes, and more preferably from 15 seconds to 5 minutes, and particularly preferably from 20 seconds to 1 minute.

[0022] One preferred method of implanting a corneal onlay onto a cornea thus comprises (i) providing a surface modified onlay with modification at its posterior surface only; (ii) placing the onlay in contact with the corneal tissue (usually after de-epithelialization as described above); and (iii) irradiating the onlay whereby the onlay is fixed on the cornea. Preferably, irradiation is limited to the area of the onlay so that exposure of the cornea is minimized.

[0023] Subsequent to the above fixation of the onlay on the cornea, the anterior surface of the implant may be coated with a tissue growth promoting compound as described hereinafter. In alternative preferred aspects, the anterior surface of the onlay may have been surface modified with tissue growth promoting compounds to promote epithelialization prior to the fixation step.

[0024] A preferred method of implanting a corneal prosthesis within a cornea comprises (i) providing a surface modified implant which has been modified at both its posterior and anterior surface, (ii) placing the implant in contact with the corneal tissue; (iii) before or after step (ii) coating the anterior surface with one or more components which promote the growth of tissue adjacent to the implanted onlay, and (iv) irradiating the onlay whereby the implant is fixed within the corneal tissues and the tissue growth promoting compound is fixed on the anterior onlay surface. In alternative preferred aspects, the anterior surface of the implant may have been surface modified with tissue growth promoting compounds to promote epithelialization prior to the fixation step.

[0025] Suitable tissue growth promoting compounds in both above mentioned methods are, for example, albumins, extracellular matrix (ECM) proteins, fibronectin, laminin, chondroitan sulfate, collagen, cell-attachment proteins, anti-gelatine factor, cold-insoluble globulin, chondronectin, epidermal growth factor, mussel adhesive protein, sialo proteins, thrombospondin, vitronectin, and various proteoglycans, and/or derivatives of the above or mixtures thereof. Other preferred tissue growth promoting compounds are kalinin, K- laminin, vitronectin, talin, integrin, albumin, insulin-like growth factor, fibroblast growth factor, hepatocyte growth factor, epithelial growth factor, transforming growth factor-. alpha., transforming growth factor- .beta., keratinocyte growth factor, heparin binding factor, fibroblast growth factor, nerve growth factor, substance P; interleukin-1 alpha, interleukin-1 beta, FAP, YIGSR, SIYITRF, PHSRN, IAFQRN, and LQVQLSIR

[0026] In preferred aspects of the present invention, the above described corneal prosthesis is chemically bonded to the cornea by irradiation with ultraviolet or visible light at a 1 -cm or less distance for up to 30 minutes. A non-toxic catalyst (polymerization initiator) such as riboflavin, rose bengal, or glucose may be used to facilitate the chemical bonding. In additional preferred aspects, the exposure of the electromagnetic waves to the prosthesis may either be completely over the prosthesis or only partly over the prosthesis. Partial exposure of the corneal prosthesis to electromagnetic waves may be all that is necessary to secure the prosthesis to the cornea and advantageously decreases exposure of the eye to electromagnetic energy.

[0027] In preferred aspects of the present invention, the corneal prosthesis may be a lens which has a corrective optical property, such as correcting refractive errors such as myopia, hyperopia, astigmatism, or higher order aberrations. The corneal prosthesis may also be multifocal to allow treatment of refractive errors as well as presbyopia. In additional preferred aspects, the corneal prosthesis corrects the refractive error by changing the curvature of the corneal tear film, by modifying the net refractive index of the cornea, or a combination of both. The average power of the cornea after implantation or attachment of the prosthesis will in preferred aspects be between 25 and 55 diopters. The shape of the corneal prosthesis which is necessary for vision correction may be achieved by molding, laser ablation, or a combination of both. In the case of laser ablation, ablation may be performed to the prosthesis prior to fixation to the eye or subsequent to fixation to the eye

[0028] In the case of correction of presbyopia and refractive error, the corneal prosthesis may have a superior area which has a curvature and/or refractive index which will give the superior cornea an effective refraction between -1.0 and -4.0 diopters. The corneal prosthesis may also have an inferior area which has a curvature and/or refractive index which will give the inferior cornea an effective refraction between 0 and -1.0 diopters. Optionally, there may be a transition zone between the superior and inferior parts of the corneal prosthesis which has a gradually changing refraction which is between the refraction powers of the superior and inferior aspects of the prosthesis. The rationale for this design, is that when a person looks straight ahead, part of the superior cornea is covered and the person effectively looks through the inferior aspect of the cornea for distance vision. Conversely, when a person looks down to read, the lower lid covers the inferior cornea and the person effectively looks through the superior cornea for near vision. When a person looks through the transition zone of the prosthesis, this will provide intermediate vision. In additional preferred aspects, the optical zone of this type of presbyopia correcting prosthesis will be between 4 and 9 mm.

[0029] In alternative preferred aspects, the corneal prosthesis may treat presbyopia by having a central optical zone of one optical power and at least one concentric zone of a different optical power to allow for correction of both distance vision and near vision. The central optical zone may have an optical power to provide clear distance vision or clear near vision. In preferred aspects, at least part of one of the concentric zone(s) would be within the pupil, usually meaning that at least part of the concentric zones(s) would be within a 2 mm radius of the center of the central optical zone. In yet other preferred aspects, the corneal prosthesis may be aspheric in design and have a gradually changing curvature , instead of discrete optical zones, which allow the focus of light from both distant and near objects. The curvature at the center of the prosthesis may provide an optical power to provide either clear distance vision or clear near vision. [0030] In further preferred aspects of the present invention, the corneal prosthesis may be colored. This advantageously allows either a permanent or reversible change in the cosmetic appearance of the eyes. Moreover, coloration of the prosthesis may be used to create an artificial iris for cosmetic purposes as well as to treat medical conditions such as traumatic or congenital aniridia. In preferred aspects, coloration of the corneal prosthesis is achieved by the presence of a color additive on the surface of the corneal prosthesis or sealed within the corneal prosthesis. These color additives may consist of one or more of the following: 1 ,4- Bis[(2-hydroxy-ethyl)amino]-9,10-anthracenedione bis(2-propenoic)ester copolymers, 1 ,4- Bis [(2-methylphenyl)amino] -9,10-anthracenedione, 1,4-Bis[4- (2-methacryloxyethyl) phenylamino] anthraquinone copolymers, Carbazole violet, Chromium-cobalt-aluminum oxide, Chromium oxide greens (CI. Vat Orange, 2-[(2,5-Diethoxy- 4-[(4-methylphenyl)thiol] phenyl)azo] -1 ,3,5-benzenetriol, C.I. Vat brown 1 : 16,23-Dihydrodinaphtho [2,3-a:2',3'-i] naphth [2',3':6,7] indolo [2,3-c] carbazole- 5,10,15,17,22,24-hexone, C.I. Vat yellow 3: N₅N¹- (9,10-Dihydro- 9,10-dioxo- 1 ,5-anthracenediyl) bisbenzamide, C.I. Vat blue 6: 7,16- Dichloro- 6,15-dihydro- 5,9,14,18-anthrazinetetrone, C.I. Vat green 1 : 16,17-

Dimethoxydinaphtho (l ,2,3-cd:3',2',l'-lm) perylene-5,10-dione, Poly(hydroxyethyl methacrylate) -dye copolymers: including one or more of C.I. Reactive black 5, C.I. Reactive blue 21 , C.I. Reactive orange 78, C.I. Reactive yellow 15, C.I. Reactive blue 19, C.I. Reactive blue 4, C.I. Reactive red 11 , C.I. Reactive yellow 86, C.I. Reactive blue 163, C.I. Reactive red 180; C.I. Solvent Yellow 18: 4-[(2,4-dimethylphenyl)azo]- 2,4-dihydro- 5- methyl-2-phenyl- 3H-pyrazol-3-one, C.I. Vat orange 5: 6-Ethoxy-2- (6-ethoxy-3-oxobenzo(b) thien-2(3H)- ylidene) benzo(b)thiophen- 3(2H)-one, Phthalocyanine green, Iron oxides, Titanium dioxide, Vinyl alcohol/methyl methacrylate-dye reaction products C.I. Reactive red 180, C.I. Reactive black 5, C.I. Reactive orange 78, C.I. Reactive yellow 15, C.I. Reactive blue 19, C.I. Reactive blue 21), Mica-based pearlescent pigments, (Phthalocyaninato(2-)) copper, D&C Green No. 6, D&C Red No. 17, D&C Violet No. 2, and D&C Yellow No. 10.

[0031] In other preferred aspects, the corneal prosthesis will have a diameter between 1 and 14 mm. More preferably, the corneal prosthesis will have a diameter between 4 mm and 12.5 mm to allow an adequate sized optical zone and/or allow complete coverage of the natural iris. For treatment of presbyopia, a smaller corneal prosthesis between 1 to 4 mm, which is located at least partially in the pupil, may be preferable to create a multifocal effect. In preferred aspects, the thickness of the onlay should be between 5 microns and 150 microns to allow the correction of a wide range of refractive errors The thickness of the prosthesis is not uniform throughout the onlay and preferably tapers to a thickness of 20 microns or less in the periphery of the prosthesis. The thinner periphery of a prosthesis, may allow easier growth of epithelium over an onlay and will decrease the empty space between the prosthesis and the corneal stroma in the case of an implant. Less empty space within the corneal stroma, advantageously decreases the likelihood of biologic debris and deposits forming around the implant.

[0032] The corneal prosthesis may also contain one or more holes or perforations within it to increase the depth of focus of the cornea and to provide a path for nutrients and oxygen. Typically, these holes would be from 1 mm to 4 mm in its largest dimension for the purposes of increasing the depth of field . The holes would typically be between 0.01 mm and .9 mm in size for the purposes of increasing the flow of nutrients and oxygen. The holes or perforations may be round or not round in shape. These holes or perforations may be distributed in the center of the corneal prosthesis, in the periphery of the prosthesis or both.

[0033] Figure 1 shows a corneal prosthesis P of the present invention in relation to cornea C. Chemical groups 10, which are found on the surfaces of corneal prosthesis P and cornea C may bond to each other in the presence of electromagnetic energy E, which in this case is ultraviolet light. Note that the chemical groups 10 do not need to be of the same type. For example, the chemical groups 10 could represent a diazopyruvamide and lysine. A nontoxic catalyst (polymerization initiator) such as riboflavin or rose bengal may be used to facilitate bonding of the chemical groups. The corneal prosthesis P is physically attached to cornea C by the chemical bonds 20 which are formed in the presence of ultraviolet or visible light. Although Figure 1 shows the attachment of an onlay to the cornea, above Bowman's membrane, the same method could be used to attach a corneal implant within the cornea below the level of Bowman's membrane.

[0034] Figure 2 illustrates the chemical reactions involved in attaching a prosthesis made of poly(2-hydroxyethylmethacrylate)-methacrylic acid (PHEMA/MAA) to a molecule of diazopyruvamide by a PEG tether. In the presence of ultraviolet irradiation in the 320 nm to 500 nm range, the diazopyruvamide undergoes a Wolff rearrangement and loses its terminal nitrogen thereby forming a reactive ketene. The reactive ketene of the diazopyruvamide then forms a covalent bond with the primary amine group of lysine or hydroxylysine on corneal collagen. In this way, a prosthesis made of PHEMA/MAA or some other optical polymer can be securely attached to the cornea. Note that in this example, no catalyst is necessary to complete the attachment process.

[0035] Figure 3 A shows a system 100 for attaching a corneal prosthesis P to the cornea C without the use of sutures. A generator 30 for electromagnetic (EM) energy, typically ultraviolet, generates electromagnetic energy which is conveyed to the prosthesis P and cornea C by fiberoptic cable 40. A handpiece 50, which is shown in side profile, allows the surgeon to easily control where the electromagnetic energy is directed. Handpiece 50 includes an energy applicator surface 55 from which the electromagnetic energy radiates.

[0036] Figure 3B shows a bottom view of the handpiece 50 and energy applicator surface 55. Note that in this case the energy transmitter 55 has a ring shape and that the energy is transmitted from the handpiece 50 only along the area shown in dashed lines in a ring fashion. This ring configuration advantageously limits the exposure of electromagnetic energy to the periphery of the prosthesis P (not shown) and cornea C (not shown), while still allowing firm attachment of the prosthesis. Although, the drawing shows the energy transmitter in a ring configuration, any configuration or shape may also be used, including a shape which completely covers the cornea. In preferred aspects, the largest dimension of the energy transmitter would be between 1 and 14 mm, more preferably between 4 and 12 mm to enable fixation of corneal prosthesis of different sizes..

[0037] Figure 4 shows a schematic view of a corneal prosthesis which is used for the treatment of presbyopia. Note that the superior aspect of the prosthesis 60 has a superior area which has a curvature and/or refractive index which will give the superior cornea an effective refraction between -1.0 and -4.0 diopters to provide for near vision. The middle of the prosthesis 70 has a transition zone with a gradual change in refraction between the powers of 0 and -1. The inferior aspect of the prosthesis 80 will also have an inferior area which has a curvature and/or refractive index which will give the inferior cornea an effective refraction between 0 and -1.0.

[0038] While the above is a complete description of the preferred embodiments of the invention, various alternatives, modifications, and equivalents may be used. Therefore, the above description should not be taken as limiting the scope of the invention which is defined by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method for immobilizing a corneal prosthesis on a cornea, said method comprising: positioning the corneal prosthesis in contact with corneal tissue, wherein at least a portion of the surface of the prosthesis displays a native cross-linking biomolecule; and irradiating the corneal prosthesis with energy under conditions selected to cross-link the native cross-linking biomolecule with endogenous moieties in the corneal tissue.

2. A method as in claim 1 , wherein the prosthesis comprises an onlay or an implant.

3. A method as in claim 1, wherein the prosthesis comprises a prosthesis body composed at least partially of one or more compounds selected from the group consisting of collagen, polyurethanes, poly(2-hydroxyethylmethacrylate), polyvinylpyrolidone, polyglycerolmethacrylate, polyvinyl alcohol, polyethylene glycol, polymethacrylic acid, silicones, polyfluorocarbons,N-isopropylacrylamide, l-ethyl-3,3" (dimethyl-aminopropyl)carbodidimide, N-hydroxysuccinimide and polymers with phosphocholine, polysiloxanes, perfluoroalkyl polyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl (meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, polyolefines, or fluorinated polyolefines, such as polyvinylidene fluoride, fluorinated ethylene propylene, or tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-l ,3-dioxol, polyhydroxyethyl methacrylate (HEMA), polyvinyl pyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, poly-N,N-dimethyl acrylamide (DMA), polyvinyl alcohol, copolymers for example from two or more monomers from the group hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid, acrylamide, N,N-dimethyl acrylamide, vinyl alcohol, vinyl acetate and the like, polyalkylene glycols such as polyethylene glycols, polypropylene glycols or polyethylene/polypropylene glycol block copolymers.

4. A method as in claim 1 , wherein the native cross-linking biomolecule is selected from the group consisting of collagen, fibronectin, laminin, kalinin, K-laminin, vitronectin, talin, integrin, albumin, insulin-like growth factor, fibroblast growth factor, hepatocyte growth factor, epithelial growth factor, transforming growth factor-α., transforming growth factor-β, keratinocyte growth factor, heparin binding factor, fibroblast growth factor, nerve growth factor, substance P; interleukin-1 α, interleukin-1 β, FAP, YIGSR, SIYITRF, PHSRN, IAFQRN, and LQVQLSIR, 1 ,8 naphthalimide, diazopyruvates, and diazopyruvamides.

5. A method as in claim 1, wherein irradiating comprises exposing the prosthesis to ultraviolet radiation or visible light.

6. A method as in claim 1 , wherein the irradiating step is performed in the presence of a non-toxic catalyst to promote cross-linking.

7. A method as in claim 6, wherein the non-toxic catalyst is riboflavin, rose bengal, or glucose.

8. A method as in claim 1, wherein at least a portion of the anterior side displays a tissue growth promotant to promote the growth of tissue over the surface of the prosthesis.

9. A corneal prosthesis comprising a polymeric body having corrective optical properties, wherein at least a portion of the surface of the optical body displays native biomolecules or derivatives of native biomolecules which cross-link with endogenous corneal moieties in corneal tissue when irradiated.

10. A prosthesis as in claim 9, wherein the prosthesis is an onlay or an implant.

11. A prosthesis as in claim 9, wherein the prosthesis body is composed at least partially of one or more compounds selected from the group consisting of collagen, polyurethanes, poly(2-hydroxyethylmethacrylate), polyvinylpyrolidone, polyglycerolmethacrylate, polyvinyl alcohol, polyethylene glycol, polymethacrylic acid, silicones, polyfluorocarbons,N-isopropylacrylamide, l-ethyl-3,3' (dimethyl- aminopropyl)carbodidimide, N-hydroxysuccinimide and polymers with phosphocholine, polysiloxanes, perfluoroalkyl polyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl (meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, polyolefϊnes, or fluorinated polyolefines, such as polyvinylidene fluoride, fluorinated ethylene propylene, or tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-l ,3-dioxol, polyhydroxyethyl methacrylate (HEMA), polyvinyl pyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, poly-N,N-dimethyl acrylamide (DMA), polyvinyl alcohol, copolymers for example from two or more monomers from the group hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid, acrylamide, N,N-dimethyl acrylamide, vinyl alcohol, vinyl acetate and the like, polyalkylene glycols such as polyethylene glycols, polypropylene glycols or polyethylene/polypropylene glycol block copolymers.

12. A prosthesis as in claim 9, wherein the native biomolecule is selected from the group consisting of collagen, fibronectin, laminin, kalinin, K-laminin, vitronectin, talin, integrin, albumin, insulin-like growth factor, fibroblast growth factor, hepatocyte growth factor, epithelial growth factor, transforming growth factor-α., transforming growth factor-β, keratinocyte growth factor, heparin binding factor, fibroblast growth factor, nerve growth factor, substance P, interleukin-1 α, interleukin-1 β, FAP, YIGSR, SIYITRF, PHSRN, IAFQRN, and LQVQLSIR, and diazopyruvamides.

13. A prosthesis as in claim 9, wherein at least a portion of the anterior side displays a tissue growth promotant to promote the growth of tissue over the surface of the prosthesis.

14. A prosthesis as in claim 9, which is colored with a biocompatible color additive.

15. A prosthesis as in claim 14, which contains one or more color additives selected from: l ,4-Bis[(2-hydroxy-ethyl)amino]-9,10-anthracenedione bis(2-propenoic)ester copolymers, 1,4-Bis [(2-methylphenyl)amino] -9,10-anthracenedione, 1 ,4-Bis[4- (2- methacryloxyethyl) phenylamino] anthraquinone copolymers, Carbazole violet, Chromium- cob alt- aluminum oxide, Chromium oxide greens (CI. Vat Orange, 2-[(2,5-Diethoxy- 4-[(4- methylphenyl)thiol] phenyl)azo] -1,3,5-benzenetriol, C.I. Vat brown 1 : 16,23- Dihydrodinaphtho [2,3-a:2',3'-i] naphth [2',3':6,7] indolo [2,3-c] carbazole- 5,10,15,17,22,24- hexone, C.I. Vat yellow 3: N,N'-(9,10-Dihydro- 9, 10-dioxo- 1 ,5-anthracenediyl) bisbenzamide, C.I. Vat blue 6: 7,16-Dichloro- 6,15-dihydro- 5,9,14,18-anthrazinetetrone, C.I. Vat green 1 : 16, 17-Dimethoxydinaphtho (l ,2,3-cd:3',2',l '-lm) perylene-5,10-dione, Poly(hydroxyethyl methacrylate) -dye copolymers: including one or more of C.I. Reactive black 5, C.I. Reactive blue 21 , C.I. Reactive orange 78, C.I. Reactive yellow 15, C.I. Reactive blue 19, C.I. Reactive blue 4, C.I. Reactive red 1 1 , C.I. Reactive yellow 86, C.I. Reactive blue 163, C.I. Reactive red 180; C.I. Solvent Yellow 18: 4-[(2,4-dimethylphenyl)azo]- 2,4- dihydro- 5-methyl-2-phenyl- 3H-pyrazol-3-one, C.I. Vat orange 5: 6-Ethoxy-2- (6-ethoxy-3- oxobenzo(b) thien-2(3H)- ylidene) benzo(b)thiophen- 3(2H)-one, Phthalocyanine green, Iron oxides, Titanium dioxide, Vinyl alcohol/methyl methacrylate-dye reaction products C.I. Reactive red 180, C.I. Reactive black 5, C.I. Reactive orange 78, C.I. Reactive yellow 15, C.I. Reactive blue 19, C.I. Reactive blue 21), Mica-based pearlescent pigments, (Phthalocyaninato(2-)) copper, D&C Green No. 6, D&C Red No. 17, D&C Violet No. 2, and D&C Yellow No. 10.

16. A prosthesis as in claim 9 which contains a superior area which has a curvature and/or refractive index which will give the superior cornea an effective refraction between -1.0 and -4.0 diopters and an inferior area which has a curvature and/or refractive index which will give the inferior cornea an effective refraction between 0 and -1.0 diopters.

17. A prosthesis as in claim 15 which contains a transition zone between the superior and inferior parts of the corneal prosthesis which has a gradually changing refraction which is between the refraction powers of the superior and inferior aspects of the prosthesis.

18. A system for bonding a corneal prosthesis to a cornea, said system comprising: an electromagnetic (EM) energy source; and a handpiece adapted to direct energy from the EM source to the cornea and corneal prosthesis.

19. A system as in claim 18, wherein the hand piece has an energy applicator surface that is shaped to conform to at least a portion of the cornea or the prosthesis.

20. A system as in claim 19, wherein the energy applicator surface is curved to conform to the curve of the cornea or prosthesis.

21. A system as in claim 19, wherein the energy applicator surface has a maximum width in the range from 1 mm to 14 mm.

22. A system as in claim 19, wherein the maximum width is in the range from 4 mm to 12 mm.

23. A system as in claim 18, wherein the EM energy source emits ultraviolet radiation or visible light.

24. A system as in claim 18, wherein the energy is transmitted by an optical fiber in the handle.

25. A method as in claim 8, wherein the growth promotant is selected from: albumine, extracellular matrix (ECM), fibronectin, laminin, chondroitan sulfate, collagen, cell-attachment proteins, anti-gelatine factor, cold-insoluble globulin, chondronectin, epidermal growth factor, mussel adhesive protein, sialo proteins, thrombospondin, vitronectin, proteoglycans, collagen, kalinin, K-laminin, vitronectin, talin, integrin, albumin, insulin-like growth factor, fibroblast growth factor, hepatocyte growth factor, epithelial growth factor, transforming growth factor-. alpha., transforming growth factor-.beta., keratinocyte growth factor, heparin binding factor, fibroblast growth factor, nerve growth factor, substance P; interleukin-1 alpha, interleukin-1 beta, FAP, YIGSR, SIYITRF, PHSRN, IAFQRN, and LQVQLSIR cell-attachment proteins, epidermal growth factor, and/or derivatives of the above or mixtures thereof