MXPA00007336A - Method and apparatus for orthoqueratology aceler - Google Patents

Abstract

An orthokeratology method is described which includes the steps to soften the cornea (10) with a softening agent, apply a mold (36) to reshape the cornea (10) to a desired anterior curvature and quickly stabilize or "fix" the tissues of the cornea so that the cornea retains its new configuration. A chemical softening agent, such as glutaric anhydride is applied to the cornea (10) to soften it, after which a specially designed mold (36) of curvature and predetermined configuration is applied to the cornea. The mold (36) is held in place while a stabilizing agent, such as a UV light source (96), is placed on the mold (36). The stabilizing agent, e.g., UV light, is applied to the cornea (10) wherein the stabilizing agent immediately stabilizes the corneal tissue so that the cornea retains its shape after removing the mold (3).

Description

METHOD AND APPARATUS FOR ACCELERATED ORTHOPERATOLOGY BACKGROUND AND BRIEF DESCRIPTION OF THE INVENTION The present invention is concerned with orthokeratology, ie the formation of the cornea to correct refractive errors and more particularly with an accelerated method of corneal tissue reformation, wherein the cornea is softened, formed with a mold and after that stabilized quickly so that the cornea immediately retains the new, corrective shape Millions of people around the world have refractive errors of the eye that forces them to wear glasses and / or lenses of corrective contact. Among the most common refractive errors are myopia (inability to see distant objects), hyperopia (inability to see near objects) and astigmatism (asymmetric inclination of the cornea by means of which the curvature is different in different planes). Each of the above defects is usually corrected by corrective eyeglasses or contact lenses. Corrective glasses correct refractive errors by changing the angle of light with a lens before it reaches the cornea. Contact lenses correct refractive errors by replacing the deformed anterior curvature of the cornea with a curvature that is calculated to return to the hyperopic eye. While eyeglasses and corrective contact lenses are highly effective in temporarily correcting these problems, that is, while glasses or contact lenses are in place, the physical defects of the cornea are never corrected and thus require the use of 5 life of glasses or contact lenses, thus, there has been a search to determine effective methods to correct the refractive errors of the eye physically altering the anterior curvature of the cornea, so that they are no longer required corrective lenses. 10 Among the many solutions to the problems of refraction of the eye are surgical procedures in which the cornea is surgically altered. While effective, existing surgical modification techniques have significant risk factors and 15 disadvantages, which include human error, infections, prolonged healing time and temporary loss of vision during recovery. In addition, there are significant psychological fears associated 'with voluntary eye surgery. The odds of Permanent damage to the eye does not usually exceed the discomfort of wearing glasses or contact lenses in most cases. For obvious reasons, invasive surgical modification of the cornea has not been very well received as a purely voluntary procedure. 25 A non-invasive technique for physically altering the The anterior curvature of the cornea that has received acceptance is laser photorefractive keratectomy, where an excimer laser is used to selectively remove (remove) outer layers of the cornea to produce a more spherical curvature. The laser method has achieved a high degree of success. However, there are certain drawbacks to this procedure, which include temporary reductions in visual acuity during healing, delayed visual recovery, pain, stromal turbidity, temporal hyperopia, nighttime glare, halos, and infectious keratitis. . A known non-surgical laser technique, orthokeratology, which forms the general basis for the present invention, involves the use of a series of progressive contact lenses which are proposed to gradually reform the cornea and produce a more spherical anterior curvature. The process usually involves adjusting three to six pairs of contact lenses and usually takes around 3-6 months to achieve optimal reformation. The theory behind orthokeratology is that the cornea is very flexible and can be physically reformed over time. The thickest layer of the cornea, known as the stroma, is made up of alternating lamellae of thin collagen fibrils that form a flexible tissue matrix. While collagen tissues are flexible, unfortunately They also exhibit a shape memory and unless lenses are used daily to maintain the desired shape, the cornea will quickly return to the original shape. (A Additional development work in the field of 5 Orthokeratology has provided accelerated orthokeratology methods where chemical, enzymatic and / or other agents are used to soften the cornea. For example, the US patents granted to Neefe Nos. 3,760,807, 3,776,230 and 3,831,604 collectively describe the The use of chemical agents such as proparcaine hydrochloride, dyclonine hydrochloride, chlorine in solution, the application of heat to the cornea through hot molds, the application of heat in the form of ultrasonic energy and the use of proteolytic enzymes to soften the cornea for your 15 reformation. In addition, the North American patents granted to Kelman and DeVore Nos. 4,713,446, 4,851,513, 4,969,912, 5,201,764 and 5,492,135 each describe various chemical agents for treating and / or softening both natural and artificial collagen materials for ophthalmic uses. From the various prior art available in this area, it is believed that the US patents granted to Harris No. 5,270,051 and 5,626,865 are the closest prior art to the subject matter of the invention, of which the applicant is aware. Harris' patents describe 25 a method to accelerate the cornea by releasing enzymes, such as hyalurodinase, to the cornea to temporarily soften or soften the cornea and then provide the cornea with a rigid contact lens, which has a curvature ifÉ that will correct the refractive error. The cornea 5 softened then reforms its curvature to the curvature of the contact lens, returning to the emetropic eye. The speed of the forming process is significantly increased by the use of the softening agent and reduces the treatment period from months to days. After the training, a The retention lens is used for a period of several days while allowing the enzyme to dissipate from the cornea and the cornea "hardens" to retain the new emetropic configuration. While the softening of the corneal tissue is 15 accelerates to reform the cornea, there has been very little success in the development of a successful method to quickly re-stabilize the corneal tissues in their new configuration after reformation. Methods ? described in the North American patents granted to Harris No. 5,270,051 and 5,626,865 simply allow the softening agent to dissipate over time and after this time the lenses can be removed. The only prior art known to the applicant in the context of corneal (active) reestablishment is the patent 25 American awarded to Neefe No. 3,760,807, which describes a method for administering oral vitamin C as a means to accelerate corneal hardening after the use of the corneal softening agent has been discontinued. However, the acceleration of the hardening of the cornea in this context possibly means reducing the hardening time from weeks to days. The present invention provides improved methods of accelerated orthokeratology that focus on the rapid re-stabilization of corneal tissues in their new configuration after reformation. The successful development of a rapid method to re-stabilize corneal tissues provides the final key step in a non-surgical alternative treatment to physically reshape the cornea. In the context of the present invention, a patient could expect to enter the doctor's office on a non-hospitalized patient basis, have the entire treatment completed within hours and leave the office with a completely reformed cornea and no need for further use of contact lenses and glasses. Generally speaking, the improved method described herein comprises a three-step process of: 1) softening or "destabilizing" the cornea with a chemical or enzymatic softening agent; 2) apply a mold to reform the cornea to a desired anterior curvature; and 3) rapidly re-stabilize the corneal tissues with a "stabilizing agent" which is effective to immediately initiate the cross-linking of the collagen matrix. The term "stabilizing agent" as used herein is intended to include both chemical agents as well as external energy, such as light energy, applied to the cornea. More specifically, the agents contemplated to re-stabilize the cornea include chemical crosslinking agents and ultraviolet light radiation, thermal radiation and visible light radiation and microwave irradiation. He The preferred method of re-stabilizing the cornea to the present comprises exposure to ultraviolet light energy, in conjunction with a photoactivator or initiator. The invention further provides a novel apparatus for use in the described methods. In the preferred method an annular graduation device is aligned and secured with a biological adhesive on the cornea to guide the delivery of the softening agents, the mold and ultraviolet light to the cornea. The graduation device preferably includes 20 a flexible annular gasket on the lower edge to prevent the escape of chemical agents introduced into the graduation device. A chemical softening agent, such as glutaric anhydride is introduced into the grading device to soften the cornea. It is known that 25 glutaric anhydride destabilizes the crosslinks between Collagen fibrils and acts to soften corneal tissue sufficiently to allow for the formation with minimal external pressure. After treatment with the chemical softener, a specially designed mold of curvature and predetermined configuration is adjusted in the graduation device. A slight downward pressure is applied to the mold for a predetermined period of time (at 1-10 minutes) to re-form the cornea. The mold is thereafter held in place while a UV light source is located above the mold within the graduation device. The mold is preferably made of a material that is transparent and does not absorb ultraviolet light, such as clear acrylic. UV light is applied to the cornea for a predetermined time, wherein the UV light cross-links the collagen fibers and re-stabilizes the corneal tissue, so that the cornea immediately 'stabilizes and retains its new shape. The stabilization stage can also be used for patients who have already undergone long-term orthokeratology to eliminate the need to continuously use a retainer to maintain the shape of the cornea. Thus, among the objects of the present invention are: the provision of an accelerated method of orthokeratology that includes a means to rapidly re-stabilize the corneal tissues after reformation; the provision of such a method where the cornea is softened with a softening agent that destabilize the collagen fibrils in the cornea; the provision of a method wherein the softened cornea is thereafter molded with a mold having a predetermined curvature and configuration; the (...) • provision of a method wherein the cornea is stabilized by applying UV light to cross-link the collagen fibril network, the provision of an apparatus for performing the method including a graduation device to limit the cornea treatment area and prevent the escape of 10 chemical agents of the treatment outside the designated area and the provision of a graduation device where the graduation device guides the application of the mold and the luminous energy of the cornea. Other objects, aspects and advantages of the invention 15 will become apparent with the description thereof when considered in connection with the accompanying illustrative drawings.

DESCRIPTION OF THE DRAWINGS In the drawings that illustrate the best mode 20 contemplated herein to carry out the present invention: Figure 1 is a cross-sectional view of a cornea undergoing treatment according to the teachings of the present invention; Figure 2 is a perspective view of a graduation device; Figure 2A is a cross-sectional view of the graduation device taken along the line 2A-2A of Figure 2; Figure 2B is a cross-sectional view of a second embodiment of the graduation device including a package thereon; Figure 2C is a cross-sectional view of a third embodiment of the grading device; Figure 3 is an elevation view of the sponge assembly; Figure 4 is a perspective view of a mold as used in the method of the present invention; Figure 5 is a cross-sectional view of the mold taken along line 5-5 of Figure 4; Figure 6 is a perspective view of a mold retainer for use in the method of the present invention; Figure 6A is a cross-sectional view thereof taken along the line 6A-6A of Figure 6; Figure 7 is a perspective view of the mold retainer and a handle, which may be attached to the mold retainer; Figure 8A is a cross-sectional view of an alternative configuration of the mold; Figure 8B is a bottom view thereof showing the dimensions of the various peripheral curved areas; Figure 8C is a bottom view of a similar mold having only a single median peripheral curve; Fig. 8D is a cross-sectional view of a mold for use in patients with hyperopia and astigmatism with composite hyperopia; Figure 8E is a cross-sectional view of yet another configuration of the mold; Figures 9-14 are cross-sectional views showing various steps of the method of the present invention; Figure 15 is a microphotograph of a cross section of the human cornea; Figure 16 is an enlargement of the microphotograph showing the collagen lamella of estrorna; Figure 17 is a schematic diagram showing a cross section of the human cornea.

DESCRIPTION OF THE PREFERRED MODALITY In accordance with the present invention, an improved method for orthokeratology is provided accelerated The improved method generally includes the three separate steps of: (1) softening the cornea so that the cornea can be formed from a first configuration to a second emetropic configuration; (2) reform the cornea by applying a mold to the cornea; and (3) re-stabilize the corneal tissues so that they remain in their new configuration. With reference to Figures 15-17, the cornea 10 is composed of 5 distinct layers of tissues, i.e. the epithelium, the Bowman's membrane, the stroma, the Descemet's membrane and the endothelium. In Figures 15 and 17, it is obvious that the thickest layer of the cornea 10 is stroma 16. The stroma is made up of alternating sheets of collagenous tissue (about 200-250 in number), the planes of which are parallel to the surface of the cornea. With reference to Figure 16, the sheets are each composed of fine collagen fibrils and proteoglycans. Collagen fibrils of alternating plates make a right angle with each other. Each lamella crosses the whole of the cornea, being around 2 microns thick. In the methods that will be described herein, chemical agents that soften, degrade or (destabilize) the structural components, are topically administered to the cornea 10. The words soften, debase and "destabilize" are interchangeable for the purposes of this Specification and all are proposed to denote a change in corneal tissue that results in the cornea 10 becoming softer and more flexible, so that the cornea can be reformed from its normal configuration to a second "emetropic" configuration very quickly .

CHEMICAL AND / OR ENZYMATIC SOFTENING AGENTS For the purposes of the present invention, any of a wide variety of chemical and / or enzymatic softening agents can be used to soften corneal tissues. As previously described in the background, the US patents granted to Neefe No. 3,760,807, 3,776,230 and 3,831,604 collectively describe the use of chemical agents such as proparacaine hydrochloride, dicllonin hydrochloride, chlorine in solution and the use of proteolytic enzymes to soften the cornea for reforming. As also previously described herein, the American patents given to Harris describe the use of enzymes, such as hyaludoinase, to soften corneal tissues. Still further, the North American patents given to Kelman and DeVore Nos. 4,713,446, 4,851,513, 4,969,912, 5,201,764, 5,354,336 and 5,492,135 each describe various chemical agents for treating and / or softening both natural and artificial collagen materials for ophthalmic uses. The teachings of all these patents with respect to chemical destabilizing agents are incorporated herein by reference, while incorporated herein, the teachings of these patents are not intended to limit the scope of the term destabilizing agent and the listings cited therein are not proposed that are limiting. Despite the multitude of different chemical agents that could be used as destabilizing agents, the preferred families of destabilizing agents include anhydrides, acid chloride, sulfonyl chlorides and sulfonic acids. The following lists of chemical agents are proposed to be representative of these types of chemical agents and are not intended to be limiting. Suitable but not limiting examples of potential anhydrides include: dichloroacetic anhydride; diglycolic anhydride, chlorodifluoroacetic anhydride; dichloroacetic anhydride, acetic anhydride, dichloro maleic anhydride, maleic anhydride; acetic anhydride, trichloroacetic anhydride, chloroacetic anhydride; acetic anhydride, D4-succinic anhydride; Chloroacetic anhydride; methyl pyrocarbonate; (acetic anhydride) -D6; iodoacetic anhydride, hexafluoroglutaric anhydride; trifluoroacetic anhydride; succinic anhydride, 3-chloro-glutaric anhydride; anhydride bromomaléico; succinic anhydride; citraconic anhydride; 2, 3-dimethylmaléic anhydride; diethyl pyrocarbonate; Itaconic anhydride; CIS-1,2-cyclobutanedicarboxylic anhydride; 3, 4-pyridinedicarboxylic anhydride; glutaric anhydride; S-acetyl mercaptosuccinic anhydride; 1-cyclopentenyl, 2-dicarboxylic anhydride; Methylsuccinic anhydride; 2- (acetylthio) succinic anhydride; 1,3-cyclopentanedicarboxylic anhydride; 1,1-bis- (2-hydroxyethyl) -urea; 2, 2-dimethylsuccinic anhydride, 2,2-dimethylglutaric anhydride; pentafluoropropionic anhydride; anhydride 3-methylglutaric; 3, 3-dimethylglutaric anhydride; anhydride (s) - (-) - (2) -trifluoroacetamido) succinic; propionic anhydride; tetrabromophthalic anhydride; CIS-aconitic anhydride; propionic anhydride; tetrachlorophthalic anhydride; 6-chlorostatic anhydride; isathoic anhydride, heptafluorobutyric anhydride; 5-nitroisathoic anhydride; EXO-3, 6-epoxy-l, 2, 3, 6-tetrahydrophthalic anhydride; 4,5-dichlorophthalic anhydride; 6-nitroisathoic anhydride; CIS-1, 2, 3, 6-tetrahydrophthalic anhydride; 3,6-dichlorophthalic anhydride; phthalic anhydride; 3-cyclohexen-1, 2-dicarboxylic anhydride; 3-chlorophthalic anhydride; phthalic anhydride; 3, 4, 5, 6-tetrahydrophthalic anhydride; 3-nitrophthalic anhydride; 3-hydroxyphthalic anhydride; 3,6-endoxohexahydrophthalic anhydride; 4-nitrophthalic anhydride; 1, 2, 3, 4-cyclobutetracarboxylic dianhydride; anhydride (+) -diacetyl-L- tartaric; 5-chloroisatoic anhydride; dianhydride tetrahydrofuran-2,3,4,5-tetracarboxylic acid; CIS-1,2-cyclohexanedicarboxylic anhydride; isobutyric anhydride; 3-methoxyphthalic anhydride; crotonic anhydride; butyric anhydride; 2-bromo-5-norbornene-2, 3-dicarboxylic anhydride; anhydride (+/-) -trans-1,2-cyclohexanedicarboxylic acid; anhydride 1, 4, 5, 6, 7, 7-hexachlor-5-norbornen-2, 3-dicarboxylic; 3-amino-5-chloro-N-methylisatoic anhydride; methacrylic anhydride; trimellitic anhydride chloride; N-methylisatoic anhydride; anhydride (+/-) - isobutenylsuccinic, 1,2,4-benzenetricarboxylic anhydride; anhydriso CIS-5-norbornen-endo-2, 3-dicarboxilico; 1,2-cyclohexanedicarboxylic anhydride; l-methyl-6-nitroisatoic anhydride; 3, 5-diacetyl-tetrahydropyran-2,4,6,6-trione; 3-ethyl-3-methylglutaric anhydrides; homophthalic anhydride; 4-methyl-1,2,3,6-tetrahydrophthalic anhydride; butyric anhydride; 4-ethylphthalic anhydride; 5-methyl-3A, 4, 7, 7A-tetrahydrophthalic anhydride; 2-furoic anhydride; 3-6-dimethyl-4-cyclohexen-1, 2-dicarboxylic anhydride; anhydride norbornance-2, 3-dicarboxylic; 2-cyanoacetyl N- (4-fluorophenyl) carbamate; endo-3,6-diethyl-3,6-endoxohexahydrophthalic anhydride; 3, 6-encoso-3-methylhexahydrophthalic anhydride; 2-cyanoacetyl N-phenylcarbamate; 2-methyl-8-oxaspiro (4.5) decane-7, 9-dione; anhydride (+/-) - hexahydro-4-methylphthalic; anhydride. 3, 6-dimethylphthalic; 8-methyl-2-oxaspiro (4.5) decan-1,3-dione; anhydride 3,3- tetramethyleneglutaric; anhydride bicyclo (2.2.2) octa-2, 5-dien-2,3-dicarboxylic acid; 3-methoxy-5-methylhexahydrophthalic anhydride; 1, 2, 4, 5-benzene-tetracarboxylic dihydride; endo-bicyclo (2.2.2) oct-5-en-2,3-dicarboxylic anhydride, trimethylacetic anhydride; 1, 2, 4, 5-benzenetracarboxylic dianhydride; methyl-5-norbornene-2, 3-dicarboxylic anhydride; valeric anhydride; 2-cyano-acyl N- (2,3-dichlorophenyl) carbamate; ethylenediaminetetraacetic dianhydride; anhydride (S) - (+) - 2-methylburiric; 2-phenylglutaric anhydride; 1, 8-naphthalic anhydride; Isova-lheric anhydride; 2-benzylsuccinic anhydride; 2, 3-naphthalic anhydride; di-tert-butyl dicarbonate; 4,7-dihydro-4,7A, 7B-trimethyl-4,7-epoxyisobenz furan-1,3 (7A, 7B) -dione; 4-mer-capto-1, 8-naphthalic anhydride; di-tert-butyl dicarbonate; 3- (tert-butyldimethylsilyloxy) glutaric anhydride; 4-sulfo-l, 8-naphthalic anhydride; di-tert-butyl dicaronate; 4-bromo-1, 8-naphthalic anhydride; 4-amino-1, 8-naphthalic anhydride; 2-cyanoethyl N- (p-tolyl) carbamate; 4-chloro-l, 8-naphthalic anhydride; 2-phthalimidosuccinic anhydride; 2-cyanoacetyl N- (4-methoxyphenyl) carbamate; 4-nitro-l, 8-naphthalene anhydride; 4-amino-3,6-disulfo-1,8-naphthalic anhydride; 2-cyanoethyl N- (3-methoxyphenyl) carbamate; 3-nitro-l, 8-naphthalic anhydride; dianhydrido bicyclo (2.2.2) oct-7-en-2, 3, 5, 6-tetracarboxilico; anhydride hexachlorohexahydro-1,4-methanonaphthalen-6,7-dicarbo-xylyl; diphenic anhydride; 2- (4-acetoxy) anhydride phenyl) succinic; N-phthaloyl-Dl-glutamic anhydride; 4- methylfuro (3 ', 4': 5, 6) naphtho (2,3-D) (1,3) dioxol-1,3 (1H, 3H) -dione; carbobenzyloxy-L-aspartic anhydride; carboben-S ^ cyloxy-L-glutamic anhydride; anhydride 5-bromo-l, 2, 3, 4-tetrahydro-l, 4-5 hetenonaphthalen-2,3-dicarboxylic acid; anhydride bicyclo (4.2.2) - dec-7-en-9, 10-dicarboxylic; 9-isopropyl-3-oxaspiro (5.5) undecan-2, 4-dione; 5-nitro-l, 2, 3, 4-tetrahydro-l, 4-ethanonaphthalen-2,3-dicarboxylic anhydride; 3- ((ethoxycarbonyl) oxycarbonyl) -2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy; FR; dianhydride 10 1,, 5, 8-naphthaletracarboxylic; 5-nitro-10-oxo-1, 2, 3, 4-tetrahydro-1,4-ethanonaphthalene-2,3-dicarboxylic anhydride; 2- (1-octenyl) succinic anhydride; FR; 1,4,5,8-naphthaletracarb-oxoyl dianhydride; 5-nitro-10-oxo-l, 2, 3, 4-tetrahydro-1,4-ethanonaphthalene-2,3-dicarboxylic anhydride; 2- L5 (1-octenyl) succinic anhydride; anhydride bis (2,6-dichlorobenzoic acid, benzoic anhydride, 3-methoxy-1,2,3,6-tetrahydro-5- (trimethylsilyloxy) phthalic anhydride, 4-bromobenzoic anhydride, 4- (2-hydroxyethylthio) -1 anhydride, 8-naphthalic, hexanoic anhydride, 3,5-dinitrobenzoyl N- (2-chlorophenyl) carbamate; 20 diethylenetriaminepentaacetic dianhydride. Suitable but not limiting examples of potential acid chloride include: propionyl chloride; methacryloyl chloride;; acryloyl chloride; methoxyacetyl chloride; methacryloyl chloride; chloride 25-methyloxalyl; heptafluorobutyryl chloride; chloride cyclopropanecarbonyl; 2,3-dichloropropionyl chloride; 4, 4, 4-trifluorocrotonyl chloride; 3- bromopropionyl chloride; fumaryl chloride; chloride? acetoxyacetyl; (+/-) -2-bromopropionyl chloride; 5,4,4,4-trifluorobutyryl chloride 5; ethyl oxalyl chloride; 2-chloropropionyl chloride; 4-bromobutyryl chloride; 3-chloropropionyl chloride; Crotonyl chloride; 4-chlorobutyryl chloride; 5- (chlorocarbonyl) uracil; ethyl malonyl chloride; 4-chlorobutyryl chloride; 2-10 thiophenecarbonyl chloride; 3-carbomethoxypropionyl chloride; butyryl chloride; 2-furoyl chloride; 3,3-dichlororpivaloyl chloride; isobutyryl chloride; Itaconic chloride; 2, 2-bis (chloromethyl) propionyl chloride; butyryl chloride; butaryl dichloride; chloride. 5-15 bromovaleryl; butyryl chloride; 3,3-dimethylacryloyl chloride; 4-morpholinecarbonyl chloride; cyclobutanecarbonyl chloride; 5-chlorovaleral chloride; chloride 5-nitro-2-furoyl; ethyl malonyl chloride; 3-chloropivaloyl chloride; trans-1, 2-cyclobutanedicarbonyl dichloride; Hexanoyl chloride; valeryl chloride; adipoyl chloride; hexanoyl chloride; isovaleryl chloride; alpha, alpha-dimethylsuccinyl chloride; tert-butylacetyl chloride; trimethylacetyl chloride; cyclopentanecarbonyl chloride; 2-ethylbutyryl chloride; chloride 3, 4-dichloro-2,5-thiophenedicarbonyl; ethylsuccinyl chloride; Benzoyl-D5 chloride; nicotinoyl chloride hydrochloride; 1-chlorocarbonyl-1-methylethyl acetate; pentafluorobenzoyl chloride; isonicotinoyl chloride hydrochloride; methyl-4- (chloroformyl) butyrate; pentachlorobenzoyl chloride; 2-thiopheniacetyl chloride; 6-bromohexanoyl chloride; 2, 3, 4, 5-tetraflurobenzoyl chloride; 2,4-difluorobenzoyl chloride; 2,6-dichlorobenzoyl chloride; 2, 3, 6-trifluorobenzoyl chloride; 3, 4-difluorobenzoyl chloride; 3, 4-dichlorobenzoyl chloride; 2, 3, 4-trifluorobenzoyl chloride; 3,5-difluorobenzoyl chloride; 3-bromobenzoyl chloride; 3, 4, 5-triiodobenzoyl chloride; 2,3-difluorobenzoyl chloride; 2-oromobenzoyl chloride; 2, 4-dichloro-5-fluorobenzoyl chloride; 3, 5-dinitrobenzoyl chloride; 4-bromobenzoyl chloride; 2, 4,6-trichlorobenzoyl chloride; 2,6-pyridinecarbonyl dichloride; 4-fluorobenzoyl chloride; 2,6-difluorobenzoyl chloride; 2, 4-dichlorobenzoyl chloride; 2-fluorobenzoyl chloride; 2, 5-difluorobenzoyl chloride; 3, 4-dichlorobenzoyl chloride; 3-fluorobenzoyl chloride; 2-nitrobenzoyl chloride; benzoyl chloride; 4-fluorobenzoyl-carbonyl-13C chloride; 2-chlorobenzoyl chloride; (s) - (-) - (trifluoroacetyl) prolyl chloride; 0.1 M solution in dichloromethane; 3- (fluorosulfonyl) benzoyl chloride; 4-chlorobenzoyl chloride; 3- (2-furyl) alanyl chloride hydrochloride; 4- (fluorosulfonyl) benzoyl chloride; chloride of 3-chlorobenzoyl; diethylmalonyl dichloride; 2-iodobenzoyl chloride; benzoyl chloride; 3-methyladipoyl chloride; 4-iodobenzoyl chloride; benzoyl chloride; pimeloyl chloride; 4-nitrobenzoyl chloride; benzoyl-carbonyl chloride-13C; cyclohexanecarbonyl chloride; 3-nitrobenzoyl chloride; benzoyl chloride; 4-methyl-4-nitrohexanoyl chloride; 4-cyanobenzoyl chloride; (+/-) -2-chloro-2-phenylacetyl chloride; heptanoyl chloride; 3-cyanobenzoyl chloride; 4-chlorophenoxyacetyl chloride; perfluorooctanoyl chloride; terephthaloyl chloride; para-toluoyl chloride; 2, 3, 5, 6-tetrachloroterephthaloyl chloride; isophthaloyl dichloride; ortho-loluyl chloride; pentafluorophenylacetyl chloride; phthaloyl dichloride; meta-toluoyl chloride; 4- (trifluoromethyl) benzoyl chloride; 1,4-phenylene bis (chloroformate); phenylacetyl chloride; 2- (trifluoromethyl) benzoyl chloride; 4- (trichloromethoxy) benzoyl chloride; phenoxyacetyl chloride; 3- (trifluoromethyl) benzoyl chloride; 2- (2,4,5-trichlorophenoxy) acetyl chloride; and M-anisoyl chloride. Suitable but non-limiting examples of potential sulfonyl chloride include 4-chlorobenzenesulfonyl chloride; 4-chloro-3- (chlorosulfonyl) -5-nitrobenzoic acid; 3-fluorosulfonylbenzenesulfonyl chloride; 4-chlorobenzenesulfonyl chloride; 3- chloride (fluorosulfonyl) benzoyl; 4-fluorosulfonyl-benzenesulfonyl chloride; 4-amino-6-chloro-l, 3-benzenedisul-fonyl chloride; 4- (fluorosulfonyl) benzoyl chloride; 0-fluorosulfonylbenzenesulfonyl chloride; 3-amino-4-chlorobenzenesulfonyl; 2-chloro-5- (fluorosulfonyl) -benzoic acid; pepsil chloride; benzenesulfonyl chloride; 4- (chlorosulfonyl) phenyl isocyanate; 4-nitrobenzenesulfonyl chloride; be censulfonyl chloride; 3, 5-dinitro-p-toluenesulfonyl chloride; 3-nitrobenzenesulfonyl chloride; 2-Acetamido-4-methyl-5-thiazolesulfonyl chloride; 4- (chlorosulfonyl) benzoic acid; 2-nitrobenzenesulfonyl chloride; 2-Nitro-4- (trifluoromethyl) benzenesulfonyl chloride; 3- (chlorosulfonyl) -oenzoic acid; 2- (Chlorosulfonyl) methyl benzoate; 8-quinolinesulfonyl chloride; alpha-toluenesulfonyl chloride; 3- (chlorosulfonyl) -p-anesic acid; 4- (2, 2-dichlorocyclopropyl) -benzenesulfonyl chloride; p-toluenesulfonyl chloride, N-acetylsulfanyl chloride; 2, 4-mesitylenedisulfonyl chloride; O-toluenesulfonyl chloride; 2, 5-dimethoxy-4-nitrobenzenesulfonyl chloride; 2-mesitylsulfonyl chloride; p-toluenesulfonyl chloride; 4-dimethylamino-3-nitrobenzenesulfonyl chloride; 6-diazo-5,6-dihydro-5-oxo-l-naphthalenesulfonyl chloride; 4-methoxybenzene sulfonyl chloride; 2, 5-dimethylbenzenesulfonyl chloride; 2,6-naphthalenedisulfonyl chloride; 3, 5-dicarboxybenzenesulfonyl chloride; 2, 5-dimethoxybenzenesulfonyl chloride; chloride 2-naphthalenesulfonyl; beta-styrenesulfonyl chloride; 5-methylsulfonyl-ortho-toluenesulfonyl chloride; 1-naphthalenesulfonyl chloride; 2, 8-dibenzofurandisulfonyl chloride; 4- (dimethylamino) azobenzene-4-sulfonyl chloride; 4-tert-butylbenzenesulfonyl chloride; 4- (4-chloro-5,7-dibromo-2-quinolyl) -benzenesulfonyl fluoride; 4-sec-butylbenzenesulfonyl chloride; 4,4'-biphenyldisulfonyl chloride; 4- (4-chloro-6-nitro-2-quinolyl) -benzenesulfonyl chloride; (+) - 10-camphorsulfonyl chloride; 4, 4'-oxybis (benzenesulfonyl chloride); 4-chloro-6-fluorosulfonyl-2- (4-nitrophenyl) quinoline; (-) -10-camphorsulfonyl chloride; 4- (phenylazo) benzenesulfonyl chloride; 4-chloro-2-phenyl-quinolin-4 ', 6-dia-sulphonyl fluoride; (+/-) -10-camphor-fonyl chloride; Dansyl chloride; 4-chloro-2-phenyl-6-quinolinesulfonyl fluoride; l-chloro-4-fluorosulfonyl-2-naphthoyl chloride; 4, 4'-methylenebis (benzenesulfonyl chloride); 2, 4, 6-triisopropylbenzenesulfonyl chloride; pentamethyl-benzenesulfonyl chloride; 2- (chlorosulfonyl) anthraquinone; 4-chloro-2-M-tolyl) -6-quinolinesulfonyl fluoride; 4-chloro-6-fluorosul-fonyl-2- (4-ethoxy-3-methoxyphenyl) quinoline; 5- (Chlorosulfonyl) -2- (hexadecyloxy) benzoic acid; 4-chloro-2- ((-olyl) -6-quinolinesulfonyl fluoride; 5,7,7-trimethyl-2- (1,3,3-trimethylbutyl) -1-octansufonyl chloride; 3-chlorosulfonyl-4-acid -hexadecyloxybenzoic acid, 5-benzoyloxy-1- (3-chlorosulfonyl-phenyl) -3-methylpyrazole; 4-chloro-2- (4- (N, N-diethyl) fluoride; aminosulfonyl) -phenyl) -6-quinolinesulfonyl; 5- (chlorosulfonyl) -2- (hexadecylsulphonyl) benzoic acid; 1-hexadecansulfonyl chloride; 2- (4-benzyloxyphenyl) -4-chloro-6-quinolinesulfonyl fluoride; Methyl 3-chlorosulfonyl-4- (hexadecyloxy) benzoate; 3- (4-chlorophenylcarbamoyl) -4-hydroxy-l-naphthalenesulfonyl fluoride; 4- (hexadecyloxy) benzenesulfonyl chloride; 3-nitro-4- (octadecylamino) benzenesulfonyl chloride; Methyl 4- (4-chloro-6-fluorosulfoni-2-quinolyl) benzoate; 4- (2,5-dichlorophenylazo) -4-fluorosulfonyl-l-hydroxy-2-naphthanilide; 4- (4-chloro-5,7-dimethyl-2-quinolyl) -benzenesulfonyl fluoride; 5-fluorosulfonyl-2- (hexadecyloxy) benzoyl chloride; Ethyl 4-chloro-2- (4-fluorosulfonyl) -6-quinolinecarboxylate; 5-chlorosulfonyl-2- (hexadecylsulphonyl) benzoyl chloride; oxalyl chloride; acetyl-2-13C chloride; chlorocarbonylsulfenyl chloride; trichloroacetyl chloride; aceti-l-13C chloride; methanesulfonyl chloride; dichloroacetyl chloride; acetyl-13C2 chloride; acetyl-D3 chloride; bromoacetyl chloride; acetyl chloride; trifluoroacetyl chloride; Chloroacetyl chloride; trichloroacryloyl chloride; oxalyl chloride; chlorosulfonylacetyl chloride; pentachloropropionyl chloride; oxalyl chloride; acetyl chloride; malonyl chloride; oxalyl chloride; acetyl chloride; and 2,3-dibromopropionyl chloride. Suitable but not limiting examples of acids Potential sulfonilics include 4,6-diamino-2-methylthiopyrimidine-5-sulfonic acid; 4-pyridylhydroxy-methanesulfonic acid; sulfoacetic acid; pyridine complex; disodium salt of 3, 3-oxetanbis (methanesulfonic acid); sodium salt of 2,5-dimethyl-3-thiophenesulfonic acid; sodium salt of 2-pyrimidine sulfonic acid; 1-fluoropyridinium triflate; Monohydrate of Month; sodium salt of 2-thiophenesulfonic acid; Salt . barium of 3-sulfoiosonicotinic acid; 3-sulfobenzoic acid; monosodium salt of (+/-) -l-hydroxy-2, 5-dioxo-3-pyrrolidine sulfonic acid; (3-methylpyridine sulfonate); 6-acetamido-3-pyridine sulfonic acid; 5-formyl-2-furansulfonic acid; 5-methyl-3-pyridine-5-phonic acid; 4-pyridinetanesulfonic acid; acid 3-pyridinesulfonic; 2-pyridinhydroxymethanesulfonic acid; 2-pyridinetanesulfonic acid; sodium salt of 3-pyridine sulfonic acid; 3-pyridylhydroxymetanesulfonic acid; calcium salt dihydrate of isonicotinic acid 2- (sulfomethyl) -hydrazide; hepes; 1- (2, 5-dichloro-4-sulfonenyl) -5-pyrazolon-3-carboxylic acid; Mops (4-morpholinopropanesulfonic acid); hepes sodium salt; 5-oxo-1- (4-sulfophenyl) -2-pyrazoline-3-carboxylic acid; Mops, sodium salt, monohydrate, (4-morpholinpropanesulfonic acid); pipes (1,4-piperazinbis- (ethanesulfonic acid); lead salt of 5-oxo-l- (4-sulfophenyl) -2-pyrazoline-3-carboxylic acid; Mopso, (beta-hydroxy-4-morpholine acid) propanesulfonic; Pipes disodium salt monohydrate; 4-chloro-3- (3-methyl-5-oxo-2-pyrazolin-1-yl) benzenesulfonic acid; 1-allyl pyridinium 3-sulfonate; N- (4-amino-S-triazin-2-yl) -sulfanilic acid; 4- (3-methyl-5-oxo-2-pyrazolin-1-yl) -benzenesulfonic acid; 1- (3-sulfopropyl) pyridinium hydroxide; sodium salt of ethyl 2-sulfobenzoate; 3- (5-imino-3-methyl-2-pirozolin-1-yl) benzenesulfonic acid; 2-pyridinaldo methyl methansulfonate ima; internal salt of 2-methyl-l-83-sulfopropyl) -pyrinium hydroxide; Pyridinium 3-nitrobenzene sulfonate; 1-piperidinepropanesulfonic acid; Epps (4- (2-hydroxyethyl) -1-piperazine-propanesulfonic acid); 3'-2-ethyl-5-phenylisoxazolium sulfonate; l-ethyl-2-methyl-3- (3-sulfopropyl) -benzimidazole; orange 74 acid; 2'-ethyl-5-phenylisoxazolium 4'-sulfonate monohydrate; sodium salt of 4- (5-hydroxy-l-phenyl-1,2,3-triazol-4-ylozo) benzenesulfonic acid; tartrazine; pyridinium p-toluenesulfonate; 1-4-dimethylpyridinium p-toluenesulfonate; yellow 34 acid; (4-aminophen-sulfopropyldithiazol-2-yn-5-ylidene) hydrazide methanesulfonic acid; 4-hydroxy-2-phenyl-6-quinolinesulfonic acid; red 19 mordant; sodium salt of 4,5-dihydroxy-3- (2-thiazolylazo) -2,7-naphthalenedisulfonic acid; 3-methoxycarbonyl-1-methylpyridinium para-toluenesulfonate; barium salt of l-phenyl-3- (3-sulfonbenzamido) -2-pyrazolin-5-one; N- (4-chlorobenzylideneamino) -sulfanilic acid pyridinium salt; salt / 3H20 of 3- (2-pyridyl) -5,6-bis (5-sulfo-2-furyl) -1, 2, 4- dina triazine, flavazin L; 2-fluoro-1-methylpyridinium p-toluene sulfonate; red 183 acid; 5-tridecyl-l, 2-oxathiolan-2, 2-dioxide; sodium salt monohydrate of N-antipyrinyl-N-methylaminomethanesulfonic acid; yellow 17 acid; 4- ((4-Chlorobenzilidene) -3-methyl-1- (4-sulfonenyl) -2-pyrazolin-5-one; blue 4 of coating; bright 3GP yellow of Cibacron; pyridine dihydrate 2-2-pyridine hydrazone acid yellow: 2-5, 6-bix-4-sulfophenyl-1,2,4-triazin-3-yl-r-sulfophenyl pyridine / 3NA / Ind.Grad., barium salt of 4- (l -benzyl-5-oxo-2-pyrazolin-3-ylcarbamoyl) benzenesulfonic acid (Bis) - (cyanoethyl) aminobenzylidene) -oxo-sulfophenyl-pyrazolinecarboxylic acid, NA; 1, 1'-ethylidepyridinium di-p-toluenesulfonate; 2,6-diamino-3- (4-82-diethylaminoethoxy) -phenylazo) pyridine methanesulfonate '; • yellow acid 76; Merocyanine 540; Palatine Fast Yellow Bln; yellow acid 25; (fluorophenyl) (sulfopropyl) thiadiazol-2-ylidene) hydrazide 1-hexadecansulfonica; 3- (2-pyridyl) -5,6-diphenyl-1,2,4-triazine-P, P'-disulfonic acid; 1-NA XH20; pyridine salt of 2-hexadecylthio-5-sulfobenzoic acid; blue 2 reactive; 2NA salt of 5-phenyl-3- (4-phenyl-2-pyridyl) -1,2,4-triazine-P, P'-disulfonic acid; H20 internal salt of Pyr Oh trans-4- (4-dibutylamino) styryl) -1- (3-sulfopropyl); 1-octadecylpyridinium p-toluenesulfonate; yellow 29 acid; sodium salt of 4- (5-oxo-3-pentadecyl-2-pyrazolin-1-yl) benzenesulfonic acid; orange 31 direct; Sefadex-Sp-C-50, exchange resin ionic; sodium salt of 4- (4- (2-hexadecyloxyphenyl) -5-oxo-2-pyrazolin-1-yl) benzenesulfonic acid; yellow 42 acid; carboxy-hexadecyloxy-benzenesulfonic acid methyl-sulfophenyl-thiadiazolinylhydraz; salt hydrate of 2,4-bis (5,684-sulfophenyl) -1,2,4-triazin-3-yl) pyridine; orange 63 acid; blue 15 reactive; Sefadex-Sp-C-25, ion exchange resin; 8-quinolinesulfonic acid; sodium salt hydrate of 8-ethoxy-5-quinolinesulfonic acid; sodium salt of 2-mercaptobenxothiazole-5-sulfonic acid; 8-hydroxyquinoline-5-sulfonic acid monohydrate; 8-ethoxy-5-quinoline-sulphonic acid; benzothiazole-2,5-disulfonic acid; N- (methylsulfonyloxy) -phthalimide; 6-methoxy-3- (3-sulfopropyl) -3H-benzothiazolin-2-one hydrazone; 2-benzofuran-sulfonic acid; l, 3-dioxo-2-isoindolene-tane sulfonic acid potassium salt; potassium salt of 4-sulfo-1, 8-naphthalene anhydride; Tech .; 2-methylthio-5-benzothiazolesulfonic acid, indole-3-acetaldehyde sodium bisulfite addition compound; sodium salt of 8-bromo-2-dibenzo-furansulfonic acid; 2-methylthiobenz-midazolesulfonic acid; 3-methyl-2-methylthio-6-nitro-5-sulfobenzothiazolium methyl sulfate; sodium salt of 8- (chloromercury) -2-dibenzofuransulfonic acid; , 2- (3-methyl-2-benzothiazolinylidene) -1-hydrazine sulfonic acid; 8-sulfo-2,4-quinoline-decarboxylic acid; 8-nitro-2-dibenzofuransulfonic acid; 8-hydroxy-7-iodo-5-quinolinesulfonic acid; Acid 6- norhamnesulfonic; dipotassium salt of 4-amino-3,6-disulfo-l, 8-naphthalic anhydride; Harman-N-sulfonic acid; Indigo carmine, certified; sodium salt monohydrate of 4-dibenzofuransulfonic acid; 4- (2-benzimidazolyl) - (• 5-benzenesulfonic acid, potassium indigo-trisulfonate, 2-dibenzofuransulfonic acid, dipotassium salt of lucifer yellow CH, potassium indigotetrasulfonate, sodium salt of 2-dibenzofuransulfonic acid, yellow lucifer CH, acid - anilino-l-naphthol-3-sulfonic acid, disodium salt of 2,8-dibenzofuransulfinic acid, sodium salt of harmine-N-sulphonic acid, para-toluenesulfonate of 2,3-dimethyl-6-nitrobenzothiazolium; , 6-dibenzofuransulfonic acid, 3- (3-sulfooxypropyl) -2,5,6-trimethylbenzothiazolium hydroxide inner salt, 3-methyl-2- (methylthio) benzothiazolium p-toluenesulfonate, 2,8-disodium salt - dibenzofurandisulfonic acid, internal salt of 1-ethyl-2-methyl-3- (3-sulfooxypropyl) -benzimidazolium hydroxide, methanesulfonic acid hydrazide (l-methyl-2-phenyl-6-sulfo-4 (1H) -quinolide) sodium salt of 2-sulfotianthene-5, 5, 10, 10-20 tetraoxide, 4- (4-quinolylazo) benzenesulfonic acid, and ethyl p-tolue 2- (methylthio) benzothiazole n-sulfonate; all of the chemical compounds listed above are available from Aldrich Chemical Company (Milwaukee, Wl). From the previous lists, it is likely that 25 preferred processes will use a simple anhydride to softening the cornea, that is to say glutaric anhydride, succinic anhydride or malic anhydride, since each of these anhydrides is hydrolyzed in rather innocuous compounds.

APPARATUS FOR APPLYING CHEMICAL AGENTS TO THE CORNEA Because it is desired to limit chemical exposure only to corneal tissues 10 of the eye, a graduation device indicated generally at 12 has been developed to limit the dispersion of liquid treatment solutions that they will be applied topically to the cornea. Referring to FIGS. 2 2A and 2B, the graduation device 12 is preferably cylindrical in shape and has upper and lower ends 14, 16 respectively and is preferably manufactured from a plastic material by injection molding. However, the graduation device 12 could also be formed from metal or fiberglass or any other suitable material. The graduation device 12 is preferably 3.81 to 5.08 cm (1.5 to 2.0 inches) in height measured between the upper and lower ends 14, 16 and has an outer diameter at the lower end 16 of between 10-15 mm. As will be appreciated by those skilled in the art, the outer diameter of the lower end generally corresponds to the diameter of the outer limbic area 17 of the cornea 10 on which the graduation device 12 will rest when in use. The side wall 18 of the graduation device 12 is preferably between 0.5-2.0 mm thick. The idea is that the grading device rests directly on the limbic area to prevent leakage of the drug solutions beyond the treated surface of the cornea 10 (see Figure 9). The graduation device 12 preferably further includes an annular elastomeric gasket 20 (FIG. 2B) which is received around the lower end 16 of the device 12 ' graduation. The elastomeric gasket 20 can be formed from a variety of non-porous elastomeric materials, such as natural and synthetic rubbers, non-porous foams, closed-cell sponges, etc. A portion 22 facing downwardly of the package 20 will engage the surface of the limbic area 17 of the cornea 10 when it is positioned to form an annular seal with the surface of the cornea 10. It is contemplated that the lower edges 34 of the lower end 16 of the graduation device 12 could be tapering slightly inward to better conform to the inclined surface of the cornea 10. Likewise, the surfaces 22 facing downwardly of the package 20 could also be inwardly tapered to provide a better fit against the surface of the the cornea. The graduation device 12 will be used for the administration of drugs to the cornea 10, as well as to guide and position the molds during the reformation. All drugs or solutions used in the methods are administered inside the grading device 12 after placement on the cornea 10 where the interface of the package 20 with the surface of the cornea seals. filtration of the solution of the interior of the device 12. To rigidly position the graduation device 12 on the cornea 10, as well as to prevent rotation thereof, a sealant or biological adhesive (not shown) can be applied to the portion 22 facing down from the package 20 to adhere the - packaging 20 to limbica 17 of the cornea 10. Any of the sealants or biological adhesives known at present would be acceptable in this context. Once the graduation device 12 is in place, the package 20 forms a seal and prevents leakage of solutions that are delivered to the center of the graduation device. In this way, the solutions and drugs are applied only to the central area of the cornea 10 that is going to be reformed. Although the preferred embodiment of the grading apparatus 12 is cylindrical, it is also contemplated that an alternative grading apparatus 12 could have a larger diameter at the upper end 14 where the outer diameter thereof is in the range from 15-35 mm ( see Figure 12). It is also contemplated that the graduation device 12 will have exterior markings 26 (Figure 2) that will allow proper rotational alignment of the graduation device 12 with respect to the eye and also the proper rotational alignment of the mold within the graduation device for error correction. of astigmatism.

ELIMINATION OF SOLUTIONS OF THE GRADUATION DEVICE Since the grading device 12 will effectively retain all the drug solutions therein, it will be necessary to selectively remove the solutions during the procedure. For example, it will be necessary to wash the cornea 10 with several buffer solutions and apply different drug solutions at different times during the procedure. For this purpose, a simple sponge absorption device (Figure 3) generally indicated at 28 has been developed, comprising a flat disc 30 having a handle portion 32 extending outwardly from an upper side thereof. The disc 32 has an outer diameter that will allow the insertion of the disc 32 inside the graduation device 12. An absorbent sponge material 34 is adhered to the underside of the disc 30 so that the sponge material 34 engages with the surface of the sponge. cornea 10 to absorb any solution within the graduation device 12 (see also figure 12).

REFORMATION After the cornea 10 is' treated with a chemical softening agent, a mold, indicated generally at 36 of predetermined curvature and configuration in adjusted in the grading device (see Figures 4-5 and 11-12). Returning to FIGS. 4-5, the mold 36 is preferably cylindrical in shape, having a mold surface generally indicated at 38 which will engage the anterior surface of the cornea 10 and furthermore has an opposite posterior surface 40. The mold 36 can be manufactured from any of a variety of materials, including metals, glass, plastic, quartz or epoxy materials. With respect to the preferred materials for manufacturing, as will be described hereinafter in example 1, the preferred method present to re-stabilize the cornea 10 after formation is by means of exposure to UV light. Thus, it is preferred that the mold 36 be made of a material permeable to UV light, such as polymethyl methacrylate. This plastic material can first be molded into a generic mold form and then have the mold surface 38 cut to a predetermined shape by a lathe. The surface 38 of the mold is provided with a predetermined geometric configuration which, when coupled with the surface of the cornea 10, is proposed to reform the cornea to an emetropic configuration. The specific details of the geometric curvature of various portions of the surface 38 of the mold will be discussed in the following. The surface 38 of the mold can be formed by any of a variety of known methods for forming optical lenses such as lathe cutting, molding or milling depending on the mold making material 36. The back surface 49 of the mold 36 is preferably provided with a key 42, so that the mold 36 can be rotationally oriented appropriately on the surface of the cornea 10. The rotation of the mold 36 can be achieved by a support tool - generally indicated at 44 having a complementary detent 46 on it. end of it (figures 6 and 6A). More specifically, the holding tool 44 has a portion 48 of the hollow cylindrical body that is proposed to be inserted into the indexing device to engage the mold 36 located therein. The retainer 46 is located at the distal end of the body portion. At the proximal end of the body portion 48 there is an enlarged diameter extractor 50 having a fluted outer surface 52 which can be easily grasped and rotated by the surgeon. The extractor is also hollow to provide a continuous opening to through the holding tool 44. Referring to Figure 7, the bra 44 is shown in conjunction with the end of a lantern 54 that will be used to apply light through the mold 36. One end of the light guide 54 is (• provided with a reduced diameter portion 56 that fits into the open end of the extractor 50 of the holding tool 44. The lantern 54 is held in an assembled relationship with the holding tool 44 by means of a set screw 58 which extends through the 10 removes 50 and engages the reduced diameter end 56 of the light guide 54. After the mold 56 is oriented in the grading device 12, pressure is applied downwardly to the mold 36 for a predetermined period of time ( 1-10 15 minutes) to re-form the cornea 10 softened. The pressure is preferably applied by pressing down on the holding tool 44 which is engaged with the mold 36 (see Figure 12). 20 MOLD CONFIGURATIONS Various types of mold configurations can be used to treat different refractive errors of the eye. In the following several configurations of the mold that can be used in the object process will be discussed. 25 (A) Residual astigmatism (internal astigmatism) The internal astigmatism is the astigmatism in the optical system of the eyes different from that measured on the corneal surface. A patient with internal astigmatism k will require the application of a curved toric central mold. 5 When the refractive astigmatism of the glasses equals cordial astigmatism at a given midpoint, the internal astigmatism is zero. That is to say that the total astigmatism of the eye is produced by the corneal toricity. Sphericalizing the cornea with a mold of the present invention will result in a 10 astigmatism of zero refraction. If the refractive astigmatism differs in magnitude but has the same direction as the corneal toricity, the difference is the internal astigmatism. There are two cases. One where the corneal cordial astigmatism is larger than the refractive astigmatism, where a bitoric mold would be used that has its most inclined curve aligned with the most inclined cordial meridian. The resulting optical product would be an emetropic with a toric cornea (the axis of cordial astigmatism would be the same pre- 20 postprocedure). The other case would be a corneal astigmatism of lesser magnitude than refractive astigmatism along the same meridian. The mold to treat this condition would have a binary theoretical curve. Astigmatism axes shape the correction 90 ° from the axis of refractive astigmatism. The mold would have a toric power equal to the difference between the power of refractive astigmatism and corneal astigmatism. The resulting optical product would be an emetropic eye with a toric cornea.

EXAMPLE A-K 's corneal 44/46 in 90 (s diopters of corneal astigmatism) -Refracture of glasses -300 = -100 x 180 (1 diopter of refractive astigmatism) -Toricity of the mold -100 x 180 EXAMPLE B -K 's' corneal 44/45 in 90 (1 diopter of astigmatism) -Refraction of the glasses -300 = -200 x 180 (2 diopters of astigmatism) -Tormicity of the mold -100 x 90 Visual optics is fundamental for those skilled in the art. The resulting internal astigmatism defined by the formula will be corrected with a bitoric mold that has a correction axis of myopia with the astigmatism axis of residual myopia. When the axis of the corneal astigmatism and the axis of the refraction of the glasses are not along the same meridian, a new axis of the bitoric mold and power can be determined by applying visual optics formulas known in the art. The spherical mold is adjusted more flat than the (* corneal astigmatic meridian by the magnitude of the 5 refraction of the glasses. The mold must have a power equal to the power of the astigmatic plane corneal meridian with a power of refraction along the meridian. This method works only if there is no residual astigmatism. When there is a residual astigmatism, a 10 toric mold having less cylinder on the same axis than the residual astigmatism. The power difference between the binary curves is equal to the magnitude of the residual astigmatism. The spherical mold component is determined by the method mentioned above. 15 (B) Spherical base curves for mold design The spherical mold is adjusted flatter than the flat corneal astigmatic meridian by the magnitude of the refraction of the glasses along the plane meridian. The r base curve of the mold must have a power equal to the power of the astigmatic corneal meridian plane minus the power of refraction along that meridian. This method works only if there is no residual astigmatism. (1) Simple myopia (a) -300 spectral refraction sph, 25 (b) corneal power of 44 sph (c) 44-3 = 41 diopters = power of the base curve of the mold. (2) Simple astigmatism (a) pl = -100 x 180 (b) 43/44 in 90 corneal powers (c) 44 (flat corneal power) - plane (0) = 44 diopters of power of the base curve of the mold. The mold is aligned on the flat corneal meridian (3) Composite myopic astigmatism (a) -200 = -100 x 180 (b) 43/44 in 90 corneal powers (c) 44-43 = 1 diopter = power of the base curve of the mold. C. Configuration of the base curve mold for hyperopia, compound hypermetropic astigmatism and presbyopia are calculated using the same formulas. The base curve of the mold is more inclined than the flat corneal meridian by the magnitude of refraction of the spectacles along the flat corneal meridian. The base curve can be spherical or aspherical or bitoric and the optical zone diameter will vary depending on the magnitude of the power correction required. The average peripheral curve will be flatter, preferably aspheric, but it can be spherical and in general will be flatter and wider when it increases the power ratio of central refraction / corneal power. That is, the more the hypermetropic refraction correction, the more inclined the central base curve and the flatter the average peripheral curve becomes. The concept of the mold (for all refractive errors) is to reconfigure a given square mm surface area of the cornea by flattening the optical zone (in the myopic) and moving the tissue laterally to the relief zone cavity, without changing the area superficial total square mm of the cornea. The overall configuration is a soft spherical optic zone (unless a bitoric curve is necessary for residual astigmatism) with a gradual relief zone that generally flattens to the natural peripheral corneal curvature.

MOLD DIMENSIONS Referring to Figures 5 and 8C, a mold configuration 36 of the general type that will be used in the processes of the present invention is shown. The mold 36 is particularly suitable for treating a short-sighted cornea wherein the object is to flatten the central portion of the cornea 10. In this respect the surface 38 of the mold includes a central curved area 60, a mean individual peripheral curve 62 (relief) and a large base 64 curve. He The width of the central curve 60 is about 4 mm and the width of the average peripheral curve 62 (relief) is between 1 mm and 1.5 mm, spherical or aspheric. The configuration of the base curve was generally discussed in the above. The average peripheral curve 62 is 2-15 diopters more inclined than the central base curve 60 for myopia corrections. The higher the base curve / k ratio (increased myopia) the more inclined and wider the peripheral (relief) curve 62 becomes. The same is true for hyperopia where the rule is that the larger the curve base / k ratio the flatter and wider the peripheral curve 62. The mean peripheral curve 62 in the molds and for hyperopia is between 2-15 diopters more flat than the curve 60 of the central base. The type and magnitude of the corneal astigmatism will influence the width and curvature of the average peripheral curve (relief) 62 in this and probably all mold designs. The larger magnitudes of composite hypermethropic astigmatism (CHA) will require flatter and wider medial peripheral curves and larger magnitudes of CMA will require steeper and wider median peripheral relief curves. Small grades of total corneal astigmatism and small spherical emetropics will require less than one difference in curvature between the central base curve and the average peripheral relief curve. The peripheral curves Aspheric stockings will optimally be used for corneas with astigmatism with inverse geometric mold designs. If an outer peripheral curve is used in the mold, it should have a width of about 0.25 mm - 2.0 mm. The curvature of the peripheral curve is somewhere near the alignment of the cornea. Referring now to FIGS. 8A-8B, a mold 36A incorporating multiple middle peripheral curves is shown. The width of the central curve 66 is between about 4-9 mm. The configuration of the central base curvature was discussed in general the above. The first curve 68 of peripheral peripheral relief (innermost curve) has a diameter of 0.3 mm to about 4.0 mm. This curve is 3-9 dioptres more inclined than the central optical zone 66. The second peripheral relief curve 70 has a width of 0.3-1.5 mm and is flatter than the first relief curve 68. If an outer peripheral curve 72 is used, it should have a width of between about 0.25 mm and 1.0 mm. This peripheral curve 72 is closer to the corneal alignment than the first average peripheral relief curve. The function of the peripheral curve 72 is to block the cornea of the structural flow outside the periphery of the mold 36A. Referring now to Figure 8D, a template 36B for use to treat hypermetropic and hypermetropic astigmatism compound is illustrated. The mold 36B is divided first into two zones, a central optical zone 74 and a middle peripheral zone indicated generally at 76. The middle peripheral zone is divided into three areas of separate curvature, i.e. a transition zone 78, an apex 80 of the curvature 76 medium peripheral and a portion 82 of external curve. Generally speaking, the central optical zone 74 is more inclined than the corneal curvature (spherical, aspheric or bitoric). Transition zone 78 is flatter than optical zone 74, but not as flat as area 80 of the apex. The apex 80 of the medial peripheral curvature 76 is maintained on the corneal surface and can be moved laterally or in the middle over the area of curvature 76. The lower curve 82 is more inclined than the curve 80 of the apex area and more aligned with the surface of the cornea 10. Referring to Figure 8E, yet another 36C configuration of the mold is illustrated for use in treating myopia or mixed myopic astigmatism. The surface 38 of the mold is provided with a central optical curve zone 84 and a middle peripheral relief zone generally indicated at 86. The central optical curve zone 84 may be spherical, aspherical or bitoric and is approximately 6.0-10 mm in diameter , with an optimal diameter of around 7 mm. The relief zone 86 is preferably divided into three areas, i.e., an inner portion 88, an apex portion 80 and an outer peripheral portion 92. The relief zone 86 middle peripheral is a concave surface that is approximately 1.5-3.0 mm wide having a variable apex site within curve 86. The inner portion 88 of the median peripheral relief curve 86 is preferably flatter than the optical zone 84 (spherical or aspherical). The apex portion 90 of the relief curve 86 is approximately 0.3-0.4 mm in width and the apex thereof may be inclined to mid or lateral sites of the relief curve 86. The outer peripheral portion 92 of the relief curve 86 is approximately 0.25-1.5 mm in width and may be more inclined than the optical zone 84 and also more inclined than the corneal curvature under the mold 36 at that site. The radius of curvature of each of the portions of the median peripheral relief zone 86 is out of alignment with the line of vision. The preferred embodiment of the mold 36C will not have an outer peripheral curve zone 92. All of the mold information described above is of the general type known in the art, for fitting contact lenses by orthokeratology. The information has been provided as a means to explain the various molds used during the described processes, but it is not proposed to limit the scope of the description to any particular type or mold structure design since many different different mold designs will function to produce he the same effect of forming the corneal tissues to the curvature of the mold to alter the refractive power of the eye. fc STABILIZATION OF THE CORNEA AFTER FORMATION The last and most crucial step in the process involves restoring the corneal tissues after reformation to the new "emetropic" configuration. For the purposes of the present description, applicants have The term "stabilizing agent" was adopted as a means to refer to all potential agents to re-stabilize the collagen matrix of the eye. Included among the stabilization agents that are going to be described in the following are the chemical stabilization agents, energy 15 luminous that includes ultraviolet and visible light, thermal radiation, microwave energy and radio waves.

RETICULATION USING UV LIGHT It is well known that UV and UVC radiation is effective in crosslinking collagen. (See U.S. Patents to Kelman and DeVore No. 4,969,912, 5,201,764, 5,219,895, 5,354,336, and 5,492,135 with respect to ultraviolet light crosslinking of collagen materials). While the exact mechanism is not fully understood, it is thought that UVC light acts primarily on tyrosine residues in the collagen molecule. Thus, the polymerization or cross-linking of the reformed corneal tissues can be carried out * by simply exposing the cornea to short wave UV light (for example 254 nm). However, the polymerization rate is not practical for this use due to the potential damage to corneal tissues caused by long-term exposure to ultraviolet light. The polymerization rate can be significantly increased by applying redox initiators 10 appropriate to the cornea before exposure to UV light. Without such an initiator, polymerization with UV light would require at least 10 minutes of exposure. Suitable but not limiting examples of some initiators include sodium persulfate, thiosulfate Sodium, ferrous chloride tetrahydrate, sodium bisulfate and oxidative enzymes such as peroxidase or catechol oxidase. A suitable dosage of the chemical initiator is one that sufficiently promotes the polymerization of the 20 corneal matrix within about 30 seconds and about 2 minutes, preferably between about 30 seconds and 1 minute, but which is insufficient to cause oxidative damage to the corneal tissues. Polymerization by UV irradiation can be 25 achieved in the short wavelength range using a standard 254 nm source between about 4 and 12 Watts. Polymerization generally occurs between about 30 seconds and about 2 minutes, preferably no more than 1 minute, at an exposure distance of about 1.5 and 5 cm of 5 distance. Because excess exposure to UV light will begin to depolymerize the collagen polymers and cause damage to the eye, it is important to limit UV irradiation for short periods. At 254 nm, the depth of penetration is very limited. 10 While the short-wave UV in the range of 254 nm is described, it is to be understood that other UV wavelengths would also be suitable depending on the application of another suitable initiator adapted to the particular wavelength. In the experiments described below, the Exposure to UV light drove without a filter, thereby providing broadband UV irradiation. LQS filters will provide a more specific wavelength, which will be suitable for an appropriate photochemical or redox initiator. The filters also reduce the temperature rise at 20 the exposure site. Sodium persulfate, which is listed as the preferred initiator in Example 1 exhibits an absorption maximum at 254 nm, but appears to be effective at much higher wavelengths. For maximum efficiency, it is preferred to adapt the UV wavelength to a specific redox or photochemical initiator.

GAMMA IRRADIATION Polymerization or crosslinking can also be achieved using gamma irradiation between 0.5 and 2.5 Mrads. However, excess gamma exposure will also depolymerize the collagen polymers.

CHEMICAL RETICULATION There are many "potential chemical" stabilization agents to be used to chemically cross-link the collagen matrix. The historical technique of collagen crosslinking uses glutaraldehyde. Glutaraldehyde and other aldehydes such as glyoxal, acrolein, acetaldehyde, butyraldehyde, propionaldehyde and formaldehyde form side-bridges between polypeptide chains and between collagen fibers. Other suitable chemical crosslinking agents but not limiting include periodates, acyl azides, ethers of Denacol14, ie polyglycidyl ether of sorbitol, polyglycidyl ether of polyglycerol, polyglycidyl ether of pentaerythritol, diglyceryl polyglycidyl ether, triglycidyl tris isocyanurate and glyceryl polyglycidyl ether, bifunctional acylating agents, including anhydrides, acyl chloride and sulfonyl chloride, for example 1,2,4,4-cyclobutetracarboxylic dianhydride, tetrahydrofuran-2,3,4,5-tetracarboxylic dianhydride, dianhydride 1, 2, 4, 5-benzenestracarboxylic acid, ethylenediaminetetraacetic dianhydride, bicyclo (2, 2, 2) oct-7-en-2,3,5,6-tetracarboxylic dichloride, glutaryl dichloride, adipoyl chloride, hydrochloride -methyldipoyl, pimeloyl chloride, terephthaloyl chloride, isophthaloyl dichloride, phthaloyl dichloride, 1,4-phenylene bis (chloroformate), 2,4-mesitylenedisulfonyl chloride, 2,6-naphthalenedisulfonyl chloride, malonyl dichloride and cross-reactive crosslinking agents of homobifunctional amine such as homobifunctional imidoesters and homobifunctional N-hydroxysuccinimidyl are also suitable. Unfortunately, many of these agents produce adverse tissue reactions and therefore their use must be carefully controlled and directed to a specific site. In this regard, chemical crosslinking is not discussed here as the preferred method of stabilization. However, such agents would be highly useful in the present method if appropriate delivery systems become available in the future.

THERMAL RADIATION Heat is another possible means of crosslinking, or (stabilization) of the corneal tissues after reformation. It is generally known that the application of heat accelerates the metabolism of tissues and will help to stabilize tissue faster than if heat were not applied. Laser thermal keratoplasty (LTK) is the use of heat produced at specific points in the stroma of the cornea by absorption of laser light to modify the structure and mechanical properties of stromal collagen. Typically, in the LTK, the laser is directed to a particular spot of the eye. As the stain absorbs light and heat up to about 55-60 ° C, the collagen will shrink. Stain rings are used to tighten the tissues to create a change in the anterior curve of the cornea. As a final step in the present methodology, the reformed cornea could be exposed to laser light where the corneal tissues would be heated and stabilized in the new emetropic configuration. The parameters of the treatment at this point in development are purely speculative.

MICROWAVE ENERGY Microwave energy is also currently being investigated as a means to treat myopia. The treatment has been called microwave thermokeratoplasty and has been previously documented by D.X. Pang, B.S. Trembly, L.R. Bartholomew, P.J. Hoopes and D.G. Camphell, Microwave Thermokeratoplasty, Investigational Ophthamology and Visual Science, 36; s988, 1995 and D.X. Pang, B.S. Trembly, L.R. Barthlomew and P.J. Hoopes, Microwave Thermokeratoplasty: Reshaping Cornea! Contour (Corneal Microwave-TKP), Acepted for Publication, International Journal of Kyperketatoplasty, (1998). See also U.S. Patent No. 4,881,543 to Trembly entitled Combined Microwave Heating and Corneal Surface Cooling (1989) and U.S. Patent No. 5,618,284 to Sand, Apparatus for Collagen Treatment (1997). The mechanism for cross-linking seems to be via the creation of heat at specific sites in the stroma. As stated above for thermal radiation, it is generally known that the application of heat accelerates the metabolism of tissues and will help to stabilize tissue faster than if heat were not applied. It is contemplated that the microwave energy could be used to generate heat in the stroma to stabilize the corneal tissues after softening and molding as described in the present invention. As a final step in the present methodology, the reformed cornea could be exposed to microwave energy, where the corneal tissues would be heated either at specific points or along the entire cornea and stabilized in the new emetropic configuration. The parameters of the treatment at this point in development are purely speculative.

APPLYING HEAT THROUGH THE MOLD Another possible technique of applying heat to the cornea it would be through direct contact with the mold. In this regard, the mold could be provided with a controlled heating element to heat the body of the mold to a predetermined temperature. Such heating could be achieved by electrical elements or by a flow of hot fluid through the mold.

RADIO WAVES It is further contemplated that radiofrequency energy could be used to generate heat in the stroma to stabilize the corneal tissues after softening and molding as described in the present invention. As a final step in the present methodology, the reformed cornea could be exposed to radiofrequency (RF) energy, where the corneal tissues would be heated either at specific points or along the entire cornea and stabilized in the new emetropic configuration. The parameters of the treatment at this point in development are purely speculative. See U.S. Patent No. 5,638,384 to Gough et al entitled "Multiple antenna ablation apparatus" (1997) which describes the use of RF energy in surgical ablation techniques.

VISIBLE LIGHT It is also possible to crosslink collagen using light visible. However, this method will require a photochemical initiator to transfer photoenergy to a chemical reaction of free radicals. The initiators of dyes • f # adequate but not limiting photochemicals include 5 fenosafranine, methyl red, bromophenol blue, crocein scarlet, phenol red, alciano blue, rose bengal, methylene blue, azure A, toluidine blue, eosin Y, evans blue, methylene green, amitest violet , lumazine, thionine, xanthoperine, 2, 3, 5-triphenyl-tetrazolium Cl, red 10 acridine, acridine orange, proflavine, rosazurin, azure B, green Bindscheder, primulin, acridine yellow, neutral red, erythrosin, fluorescein, indo-oxin and malachite green. Of these chromophores, fluororescein, eosin, indo-oxin and rose bengal seem to be more 15 suitable for corneal use. It is noted that the exposure times for these chromophores are excessive and therefore, the use of these chemical agents may not be practical in current use. However, its use is being tested r for optimal efficiency times. 20 It is thought that redox initiators will work much faster. Suitable but not limiting redox initiators include diphenylamine, eriglaucin A, ferrous ion 2, 2'-dipyridyl and N-phenylanthranilic acid. 25 STABILIZATION WITH VISIBLE LIGHT FOLLOWING DESTABILIZATION USING A SULPHONIC ACID CHROMOPHORIDE An alternative technique to reshape the cornea may comprise destabilizing the cornea with a sulfonic acid dye, followed by reshaping the cornea and stabilizing the cornea by exposure to a wavelength Specific visible light that corresponds to a maximum observance of the chromophore linked to amines reacted in the softening process. Suitable but not limiting sulfonic acid dyes include: lucifer yellow, direct yellow 8, 2, 2 '-azinobis (3-ethylbenzthiazolin-6-sulfonic acid), 4,5-dihydroxy-3- (4-sulfonaphthylazo) acid 2-naphthalenesulfonic acid, 2-dibenzofuransulfonic acid, l- (2-hydroxyethyl) quinilino p-toluenesulfonate, bright sulfaflavine, thiazine red r, pyrogallol red, papaverine sulphonic acid, direct yellow 27, naphthylazoxin a, l-ethyl acid -2-undecyl-5-benzamidazolesulfonic, hoechst 2495, 8-hydroxy-7- (4-sulfo-1-naphthylazo) -5-quinolinesulfonic acid, 3-hydroxy-4- (2-hydroxy-4-sulfo-1) -nafti-azo) -2-naphthalenecarboxylic, (methyl-sulphto-benzothiazolinylidene) hydrazide 1-hexadenesulfonic acid, sodium hydrate sulfobromophthalein, permulin, sulforhodamine 9, 8-hydroxy-5- (1-naphthylazo) -2-naphthylenesulfonic acid, 2-methylthio-3-phenylbenzothiazolium para-toluenesulfonate, 2- (m-aminophenyl) -1-dodecylbenzyl- midazole-5-sulfonic acid, 2- (4-bromobenzyl) isothiothiouronium, 8- (4-hydroxy-l-naphthylazo) -2-naphthalenesulphonate, (m-sulfo-bz-thiazolinylidene) hydrazide (hexadecyl-methylsulfamoyl) - benzenesulfonic, merocyanine 540, black F sulfon fast, 2- (3-amino-3-methylpentyl) -l-octadecyl-5-benzimidazole-sulfonic acid, sulforhodamine b, 3,6-bis- (4-sulfo-l- naphthylazo) -4,5-di-oh-2,7-naphthylenedisulfonic acid, copper phthalocyanine 3-way, 4 ', 4", 4' '' -tetrasulfonic acid, 1-hexadenesulfonic acid, 4- (hexadecylsulfamoyl) benzene sulfonic acid, phthalocyanine sulfonic acid nickel, azocarmine g, sulforhodamine 101 hydrate, 6,6'- (1,1'-biphenyl44'-diylbisazo) bis (4-amino-5-hydroxy-13-naphalendi-so-3-honeone) salt, azocaxamine b, carboxy-hexadiciloxybenzenesulphonic acid, 1-hexadecansulfonic acid, yellow g thiazole, carboxy-hexadecylsulphonylbenzenesulfonic acid, 1-hexadenesulfonic acid, clorazol azurine, 3-methyl-2-benzothiazolinone azine, brometi blue ltimol, reactive blue 15, acetamidohexadecylsulphonylbenzenesulfonic acid, owens blue, direct yellow 29 and indocyanine green.

EXAMPLE 1 Preferred Methodology (1) Apply the graduation apparatus 12 to the eye (figure 9); (2) Pre-treat the cornea (10-shown in solid lines) with 0.02 M disodium phosphate buffer (94), pH 8.5 for 1 minute (Figure 9); (3) Remove the excess buffer solution (94) with the sponge apparatus (28) (see figure 10); (4) Treat the cornea (10) with a solution containing 5-50 mg of dissolved glutaric anhydride immediately before application in 1 ml of 0.02 M disodium phosphate, pH 8.5. The preferred concentration of glutaric anhydride is 10-30 mg per ml of disodium phosphate; (5) Remove the anhydride solution with the sponge apparatus; (6) C locar a forming mold (36) in the grading apparatus 12, rotate the desired position using the holding tool 44 and apply the appropriate pressure to achieve the desired anterior curvature of the cornea (10) (see figure 12) (the original corneal shape is now shown in dashed lines and the new second configuration is shown in solid lines); (7) With the mold 36 in place, treat the cornea with a redox initiator in a slightly alkaline buffer solution. For sodium persulfate, preferably use 0.1 M sodium persulfate at 0.5 M in 0.02 M phosphate buffer pH 8.0. The preferred concentration of sodium persulfate is 0.2 M a 0. 4 M; (8) With the mold 36 still in place, exposing the corneal surface to UV radiation in the range of 250-390 nm. Preferably the Novacure EFOS unit is used and set at 3000 mW / cm2 for 10-120 seconds, preferably 30-60 seconds. The light guide 96 of EFOS is located within the grading apparatus 12 at a distance of 0.635-7.62 cm (0.25-3.0 inches) from the cornea, optimally 0.635-2.54 cm (0.25-1.0 inches). The exposures can be in the range from 2500 mW x 120 seconds to 4500 mW x 45 seconds, preferably 2500 mW x 75 seconds at 4500 mW x 30 seconds (Figure 13); (9) Following UV exposure, the cornea is completely washed with 0.02 M phosphate buffer at pH 7.2; and (10) The mold 36 and the grading apparatus 12 are then removed from the eye and the eye is examined using slot lamp and corneal topography methods to determine the degree of curvature change and determine if an additional shaping may be required ( figure 14). The original curvature of the cornea is shown in figure 14 in dashed lines, while the new curvature (emetropic) is shown in continuous lines.

STABILIZATION OF LONG-TERM ORTHOPERATOLOGY PATIENTS One of the anticipated benefits of the stabilization process is that it can be used to stabilize the corneas of patients who have already undergone long-term orthokeratology. Stabilization procedures will eliminate the need to continue using retention lenses to maintain the shape of the cornea. While it may be possible to simply use the stabilization stage for these patients, it is anticipated that the cornea will have to be destabilized before it can be restabilized to take the new configuration. In such a method, the eye would be destabilized using the methodology described above. Because the eye has already been formed previously, it will be necessary to form a poorly formed eye to reform the eye to the appropriate configuration. However, a mold would be used to maintain the proper shape during the re-stabilization process. With the mold in place, the eye would then be exposed to a photoinitiator and exposed to UV light to re-stabilize the cornea in the new configuration.

EXPERIMENT 1 The experiments were carried out using enucleated pig eyes. The pre-treatment and post-treatment evaluations of the eyes were done by lamp examination slot and taking K readings. In one control portion of the experiment, several pig eyes were treated with contact lenses only. Neither the destabilization nor the stabilization were performed on the control eyes. As expected, there was no change in the corneal curvature, determined by slot lamp examination and measurements of the K readings. In a second part of the experiment, contact lenses were applied to two eyes without destabilization, followed by treatment with solution of sodium persulfate (photochemical initiator) and exposure to UV light using an Ultracure 100SS Plus UV UV light source manufactured by EFOS of Williamsville, NY. The light dosage was about 1500 mWatts for about 30 seconds (wide wavelength of 25-390 nm). The pre-treatment measurements of the two eyes were 36.75 / 37.5. After the treatment, the measurements were 43 / 41.5 and 40.5 / 44. The eyes were clear and the rim created by the contact lenses was visible after 1 hour. In a third part of the experiment, one eye was treated with a phosphate buffer solution of pH 8.76 for 1 minute, followed by exposure to 10 mg / ml glutaric anhydride and in phosphate buffer for 1 minute to destabilize the cornea. A contact lens was applied. The eye was then washed with phosphate buffer, pH 7.2 to remove the residual glutaric acid and then rinsed with phosphate buffer (0.02 M, pH 8.0) containing 0.3 M sodium persulfate. UV light was applied for 30 seconds, the lenses were removed and the eye was washed again with phosphate buffer pH 7.2. The pre-treatment measurements of the eye were 36.75 / 37.5. The pig's eye was examined after treatment with glutaric anhydride and the measurements were 40.5 / 39.0. After treatment with UV light, the measurements were too inclined to be read and were rather distorted. The indentations and flanges created by the lenses were observed immediately after treatment and 1 hour after treatment. The results showed definitive changes in curvature ** / very obvious rims created by the lenses.

EXPERIMENT 2 The second set of experiments also used enucleated pig eyes. A topographic system of EYESYS was available to make the topographic maps of the eyes before and after the treatment. In addition, the ultracure 100SS EFOS was available for UV light treatment. In one control part of the experiment, one eye was examined using a slot lamp and using the EYESYS system. Neither anhydride nor sodium persulfate were administered before the application of UV light exposure. However, solutions were administered shock absorbers to simulate the complete treatment. The evaluation of EYESYS showed that the surface characteristics following the treatment remained the same as before the treatment. In a second part of the experiment, a second pig's eye was examined by slot lamp and EYESYS. The topographic profiles were printed. The eye was then rinsed in pH * 8.5 phosphate buffer for 2 minutes. Glutaric anhydride was prepared at 10 mg / ml in an alcoholic solution and immediately administered to the eye. A contact lens was applied to the eye and held in place for 1 minute, the eye was then rinsed in a solution of sodium persulfate (0.3 M sodium persulfate in buffer solution of pH 8.5) with the lens still in place . After several (1) minute rinses in the sodium persulfate solution, the eye was exposed to UV light for about 30 seconds. The lens was removed and the eye was washed with phosphate buffer pH 7.2. The eye was then examined by slot lamp and EYESYS. The slot lamp examination showed that the eye had developed some turbidity (probably due to the alcohol solution containing the glutaric anhydride). The EYESYS test showed that the topography of the eye has been changed. In a third part of the experiment, a third eye was treated in the same manner as above, except that the anhydride glutaric acid was administered in a phosphate buffer, pH 8.5, in an attempt to prevent the turbidity observed using alcohol. Slit lamp examinations showed much less turbidity in the cornea. Examinations with EYESYS showed topographic changes that seemed to adapt to the curvature of the applied contact lens. The experiments show that the techniques described could alter the shape of the anterior curvature of the cornea.

EXPERIMENT 3 The third set of experiments was done using a live rabbit. Ababos the EYESYS topographic system and the ultracure 100SS EFOS were available. The eyes of the rabbit were examined by slot lamp and EYESYS. The topographic profiles were printed. The control eye was left untreated. The experimental eye was exposed to 0.02 M phosphate buffered solution, pH 8.5 and treated with glutaric anhydride in 20 mg / ml in phosphate buffered solution pH 8.5 followed by application of a contact lens. The eye was then washed with 0.02 M phosphate buffer, pH 8.5 to remove residual glutaric acid, rinsed with buffer solution containing 0.3 M sodium persulfate and exposed to UV light by two 30 second exposures with the lens. contact in your place. Both eyes, the control and the treated were examined with a slot lamp and EYESYS. The topographic profiles were printed. The treated eye showed an obvious change in surface topography. The slot lamp examination indicated some corneal turbidity, which cleared in about 1 hour. The experiment, in a living animal, showed that the anterior corneal curvature could be altered in a living subject using the techniques described. Thus, it can be seen that the present invention provides a unique and effective method for rapidly modifying the anterior curvature of the cornea with non-invasive surgical techniques. The three-stage process of destabilizing, shaping and re-stabilizing will allow potential patients to have refractive vision errors corrected in a matter of hours, without a period of recovery, rather than endure the often painful prolonged procedures that currently exist. The unique method of re-stabilizing the cornea significantly decreases treatment time and stabilizes the cornea in a corrected emetropic configuration that will eliminate the need for supportive lenses or any other corrective lens for this case. As stated above, the unique aspects of the method are believed to reside in the only three stages, destabilization, reformation and stabilization and in the apparatus used to achieve the method. It has not been provided in the technique a simple, non-surgical, non-invasive and rapid treatment for refractive errors of the eyes and the present invention is believed to have solved the problems of the prior art. For these reasons, it is believed that the present invention presents a significant advance in the art, which has a substantial commercial merit. While certain specific structures comprising the invention have been shown and described herein, it will be apparent to those skilled in the art that various modifications and rearrangements of the parts can be made without departing from the spirit and scope of the underlying or fundamental inventive concept and that it is not limited to the particular forms described herein shown and described except as indicated by the scope of the appended claims.

Claims (1)

1. CLAIMS 1. A method for correcting refractive errors of the eye characterized in that it comprises the steps of: rF > destabilize the corneal tissue of the eye so 5 that the anterior curvature of the cornea can be reformed • from a first configuration to a second desired configuration; forming the softened cornea from the first configuration to the second desired configuration. 10 applying a mold to the cornea and applying pressure thereto, the mold has a predetermined posterior curvature and configuration that engages with the anterior curvature of the cernea; and re-stabilizing the corneal tissues while the anterior curvature of the cornea is located in the second desired configuration. 2. The method of compliance with the claim 1, characterized in that the stage of destabilization of the corneal tissues comprises administering to the cornea an agent 20 of softening that is effective to destabilize the cross-linking between the collagen fibrils of the corneal stroma. 3. The method of compliance with the claim 2, characterized in that the softening agent is selected from the group consisting of: anhydrides, acid chloride, sulfonyl chloride, sulfonic acids and combinations thereof. 4. The method according to claim 1, characterized in that the stage of reestabilization of the corneal tissues comprises exposing the corneal tissues to light energy. 5. The method according to claim 1, characterized in that the stage of reestabilization of the corneal tissues comprises heating the corneal tissues. 6. The method of compliance with the claim 1, characterized in that the heating of the corneal tissues comprises heating by thermal laser keratoplasty. The method according to claim 1, characterized in that the step of re-stabilizing the corneal tissues comprises administering to the cornea a chemical cross-linking agent which is effective to crosslink between the collagen fibrils of the corneal stroma. 8. The method according to claim 1, characterized in that the stage of reestabilization of the corneal tissues comprises exposing the corneal tissues to microwave energy. The method according to claim 4, characterized in that the stage of reestabilization of the corneal tissues comprises exposing the corneal tissues to visible light energy. 10. The method according to claim 4, characterized in that the stage of reestabilization of the corneal tissues comprises exposing the corneal tissues to UV light energy. The method according to claim 4, characterized in that it also comprises the step of applying a chemical photoinitiator * to the eye to rapidly initiate cross-linking of the collagen matrix. 12. The method in accordance with the claim 2, characterized in that the stage of reestabilization of the corneal tissues comprises exposing the corneal tissues to luminous energy'UV. The method according to claim 12, characterized in that it further comprises the step of administering a photochemical initiator to the eye to rapidly initiate cross-linking of the collagen matrix. The method according to claim 2, characterized in that the step of administering the chemical softening agent comprises the steps of locating the lower edge of the annular grading device to the surface of the cornea so that the grading device circulates the area of the cornea to be treated and administering the chemical softening agent to the interior of the graduation device. 15. The method in accordance with the claim 14, characterized in that the step of reforming the cornea comprises locating the mold inside the grading device and applying downward pressure for a predetermined period of time. 16. The method of compliance with the claim 15, characterized in that the mold is manufactured from a transparent material and can transmit ultraviolet light and the stage of reestabilization of the corneal tissues comprises placing a source of ultraviolet light inside the device of graduation on top of the mold and energize the light source for a predetermined period of time by means of which UV light passes through the mold to the corneal tissues. 17. The method of compliance with the claim 14, characterized in that the stage of reestabilization of the corneal tissues comprises placing a source of ultraviolet light inside the grading device and energizing the light source for a predetermined period of time by means of which light is directed on the corneal tissues. 18. The method of compliance with the claim 16, characterized in that it further comprises the step of administering a photochemical activation agent to the cornea before exposing the cornea to light dosing ultraviolet. The method according to claim 17, characterized in that it further comprises the step of administering a photochemical activation agent to the cornea before exposing the cornea to the dosing of ultraviolet light. 20. A method for correcting refractive errors of the eye characterized in that it comprises the steps of: placing a lower edge of an annular grading device to the surface of the cornea, so that the grading device circulates the area of the cornea that goes to be treated; administering a chemical softening agent to the interior of the grading device wherein the chemical softening agent is effective to destabilize the cross-linking between the collagen fibrils of the corneal stroma so that the anterior curvature of the cornea can be reformed from a first configuration to a second desired configuration; reforming the softened cornea from the first configuration to the second desired configuration by applying a mold to the cornea, the mold has a predetermined posterior curvature and configuration that engages with the anterior curvature of the cornea, the mold is located within the graduation device and after this pressure is applied down for a predetermined period of time to achieve reforming; and re-stabilizing the corneal tissues while the anterior curvature of the cornea is placed in the second desired configuration by exposing the corneal tissues to a predetermined dosage of ultraviolet light. The method according to claim 20, wherein the mold is made of a transparent material and can transmit ultraviolet light and the stage of reestabilization of the corneal tissues comprises placing a source of ultraviolet light inside the graduation device over the upper part of the mold and energize the light source for a predetermined period of time, by means of which the light passes through the mold to the corneal tissues. 22. A method for correcting refractive errors of the eye characterized in that it comprises the steps of: reforming the cornea from a first configuration to the second desired configuration by sequentially applying a series of orthoptic contact lenses having predetermined curvatures and predetermined configurations to return emetropic to the cornea; and to re-stabilize the corneal tissues while the anterior curvature of the cornea is placed in the second desired configuration exposing the corneal tissues to a predetermined dosage of ultraviolet light; 23. The method according to claim 22, characterized in that the corneal tissue stabilization step comprises locating the lower edge of an annular grading device to the surface of the cornea, so that the grading device circulates the area of the cornea. the cornea to be treated, placing a source of ultraviolet light within the graduation device and energizing the light source for a predetermined period of time, by means of which light is directed on the corneal tissues. 24. The method according to claim 22, characterized in that it further comprises the step of washing the cornea with a slightly alkaline buffer solution prior to the re-stabilization of the cornea. 25. The method according to claim 24, characterized in that the alkaline buffer solution contains a chemical photoactivator to aid in the stabilization of the corneal tissue. 26. A grading device for use in the treatment of corneal eye tissues comprising a substantially cylindrical tube having upper and lower edge portions, the lower edge portion having an outer diameter of between about 10 mm and about 15 mm. mm, the lower edge portion is placed over the eye to circulate the area of the cornea that is going to be treated. 27. The graduation device according to claim 26, characterized in that the portion of ? lower edge is tapered inward at an angle 5 predetermined to fit the curved surface of the eye. 28. The graduation device according to claim 26, characterized in that it further comprises a flexible package on the lower edge portion of the In a tube, the package forms a flexible, water-impermeable seal between the lower edge portion of the tube and the eye surface, to prevent the solutions delivered from the grading device from escaping below the lower edge portion. 29. The grading device according to claim 26, characterized in that the outer surface of the tube includes orientation marks to assist in the proper positioning of the grading device r on the eye.