Methods for accelerated orthokeratology

An accelerated method of orthokeratology includes the steps of softening of the cornea with a softening agent, applying a mold to reshape the cornea to a desired anterior curvature, and rapidly restabilizing or "fixing" the corneal tissues so that the cornea retains its new configuration. A chemical softening agent, such as glutaric anhydride is applied to the cornea to soften the cornea, after which a specially designed mold of predetermined curvature and configuration is applied to the cornea. Slight downward pressure is applied to the mold for a predetermined period of time to re-shape the cornea. The mold is maintained in position while a stabilizing agent, such as a UV light source, is positioned above the mold. The stabilizing agent, i.e. UV light, is applied to the cornea for a predetermined time, wherein the stabilizing agent immediately restabilizes the corneal tissue so that the cornea immediately retains its shape upon removal of the mold. The stabilization process can also be used for patients having already undergone traditional orthokeratology to eliminate the need to continue wearing a retainer to maintain the shape of the cornea.

BACKGROUND AND SUMMARY OF THE INVENTION 
The present invention relates to orthokeratology, i.e. shaping of the 
cornea to correct for refractive errors, and more particularly to an 
accelerated method of reshaping the corneal tissues wherein the cornea is 
softened, shaped with a mold, and thereafter rapidly stabilized so that 
the cornea immediately retains the new shape. 
Millions of people worldwide have refractive errors of the eye which cause 
them to seek out corrective eyeglasses and/or contact lenses. Among the 
most common refractive errors are myopia (inability to see distant 
objects), hyperopia (inability to see near objects), and astigmatism 
(asymmetric sloping of the cornea whereby the curvature is different in 
different planes). Each of the above-noted defects is usually corrected by 
means of corrective eyeglasses or contact lenses. Corrective eyeglasses 
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 misshapen anterior curvature of the cornea with a curvature 
which is calculated to render the eye emmetropic. While corrective 
eyeglasses and contact lenses are highly effective for temporarily 
correcting these problems, i.e. while the glasses or contacts are in 
place, the physical defects of the cornea are never corrected and thus 
require lifetime wear of the glasses or contacts. Accordingly, there has 
been an ongoing search for effective methods of correcting refractive 
errors of the eye by physically altering the anterior curvature of the 
cornea so that corrective lenses are no longer required. 
Among the many solutions to refractive eye problems are surgical procedures 
in which the cornea is surgically altered. While effective, the existing 
surgical modification techniques have significant risk factors and 
drawbacks, including human error, infection, long healing time, and 
temporary loss of sight during recovery. Furthermore, there are 
significant psychological fears associated with voluntary eye surgery. The 
chances of permanently damaging the eye do not usually outweigh the 
discomfort of wearing glasses or contacts in most cases. For obvious 
reasons, invasive surgical modification of the cornea has not been well 
received as a purely voluntary procedure. 
A non-invasive technique for physically altering the anterior curvature of 
the cornea which has received acceptance is Laser Photorefractive 
Keratectomy wherein an excimer laser is used to selectively strip away 
(ablate) 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, including temporary reductions of 
visual acuity during healing, delayed visual recovery, pain, stromal haze, 
temporary hyperopia, night glare, halos, and infectious keratitis. 
A lesser known non-surgical technique, orthokeratology, which forms the 
general basis for the present invention, involves the use of a series of 
progressive contact lenses that are intended to gradually reshape the 
cornea and produce a more spherical anterior curvature. The process 
usually involves the fitting of 3 to 6 pairs of contact lenses, and 
usually takes approximately 3-6 months to achieve optimal reshaping. The 
theory behind Orthokeratology is that the cornea is very pliable and can 
be physically reshaped over time. The thickest layer of the cornea, known 
as the stroma, is formed from alternating lamella of fine collagen fibrils 
which form a pliable matrix of tissue. While the collagen tissues are 
pliable, they unfortunately also exhibit shape memory, and unless retainer 
lenses are worn daily to maintain the desired shape, the cornea will 
rapidly regress to the original shape. 
Additional development work in the field of orthokeratology has yielded 
accelerated methods of orthokeratology wherein chemical, enzymatic and/or 
other agents are used to soften the cornea. For example, the Neefe U.S. 
Pat. Nos. 3,760,807, 3,776,230 and 3,831,604 collectively describe the use 
of chemicals such as proparacaine hydrochloride, dyclonine hydrochloride, 
chlorine in solution, the application of heat to the cornea through heated 
molds, the application of heat in the form of ultrasonic energy, and the 
use of proteolytic enzymes to soften the cornea for reshaping. 
Furthermore, the Kelman and DeVore U.S. Pat. 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. 
Of the various prior art available in this subject area, the Harris U.S. 
Pat. Nos. 5,270,051 and 5,626,865 are believed to be the closest prior art 
to the subject matter of the invention of which the applicant is aware. 
The Harris patents describe a method of accelerated shaping of the cornea 
by releasing enzymes, such as hyalurodinase, into the cornea to 
temporarily soften the cornea, and thereafter fitting the cornea with a 
rigid contact lens which has a curvature that will correct the refractive 
error. The softened cornea then reshapes its curvature to the curvature of 
the contact lens rendering the eye emmetropic. The speed of the shaping 
process is significantly increased by the use of the softening agent, and 
reduces the treatment period from months to days. After shaping, a 
retainer lens is worn for a period of several days while the enzyme is 
allowed to dissipate from the cornea, and the cornea "hardens" to retain 
the new emmetropic configuration. 
While softening of the corneal tissues does speed in reshaping of the 
cornea, there has been very little success in developing a successful 
method of rapidly restabilizing the corneal tissues in their new 
configuration after reshaping. The methods as described in the Harris U.S. 
Pat. Nos. 5,270,051 and 5,626,865 simply allow the softening agent to 
dissipate over time, after which time the lens can be removed. The only 
prior art known to the Applicant in the context of "active" corneal 
restabilization, is the Neefe U.S. Pat. No. 3,760,807 which describes a 
method of administering oral Vitamin C as a means for speeding the 
hardening of the cornea after use of the corneal softening agent has been 
discontinued. However, speeding up the hardening of the cornea in this 
context means to possibly reduce the hardening time from weeks to days. 
The instant invention provides improved methods of accelerated 
orthokeratology which focus on rapidly restabilizing the corneal tissues 
in their new configuration after reshaping. The successful development of 
a rapid method of restabilizing the corneal tissues provides the final key 
step in a rapid non-surgical treatment alternative for physically 
reshaping of the cornea. In the context of the present invention, a 
patient could expect to enter the doctor's office on an outpatient basis, 
have the entire treatment completed within hours, and leave the office 
with a completely and reshaped cornea and no need for further use of 
contacts or glasses. 
Generally speaking, the improved method as described herein comprise a 
three step process of: 1) softening or "destabilizing" the cornea with a 
chemical or enzymatic softening agent; 2) applying a mold to reshape the 
cornea to a desired anterior curvature; and 3) rapidly restabilizing the 
corneal tissues with a "stabilizing agent" which is effective for 
immediately initiating 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 contemplated agents for restabilizing the 
cornea include chemical cross linking agents, ultraviolet irradiation, 
thermal radiation, visible light irradiation, and microwave irradiation. 
The preferred method of restabilizing the cornea presently comprises 
exposure UV light energy, in conjunction with a photoactivator or 
initiator. The invention further provides novel apparatus for use in the 
described methods. 
In the preferred method an annular staging device is aligned and secured 
with a biological glue over the cornea for guiding delivery of the 
softening agents, mold and UV light to the cornea. The staging device 
preferably includes an annular flexible gasket on the lower rim to prevent 
leakage of the chemicals introduced into the staging device. A chemical 
softening agent, such as glutaric anhydride is introduced into the staging 
device to soften the cornea. Glutaric anhydride is known to destabilize 
cross-links between the collagen fibrils, and acts to soften the corneal 
tissue enough to allow shaping with minimal external pressure. After 
treatment with the chemical softener, a specially designed mold of 
predetermined curvature and configuration is fitted into the staging 
device. Slight downward pressure is applied to the mold for a 
predetermined period of time (1-10 minutes) to re-shape the cornea. The 
mold is thereafter maintained in position while a UV light source is 
positioned above the mold within the staging device. The mold is 
preferably fashioned from a material which is transparent and non-UV 
absorbing, such as clear acrylic. UV light is applied to the cornea for a 
predetermined time wherein the UV light cross-links, the collagen fibrils 
and restabilizes the corneal tissue so that the cornea immediately and 
retains its new shape. The stabilization step can also be used for 
patients having already undergone long term orthokeratology to eliminate 
the need to continue wearing a retainer to maintain the shape of the 
cornea. 
Accordingly, among the objects of the instant invention are: the provision 
of an accelerated method of orthokeratology including a means for rapidly 
restabilizing the cornea tissues after reshaping; the provision of such a 
method wherein the cornea is softened with a softening agent which 
destabilizes the collagen fibrils in the cornea; the provision of such a 
method wherein the softened cornea is thereafter molded with a mold having 
a predetermined curvature and configuration; the provision of such a 
method wherein the cornea is stabilized by applying UV light to cross-link 
the collagen fibril network; the provision of apparatus for performing the 
method including an staging device for limiting the treatment area of the 
cornea and preventing leakage of treatment chemicals outside of the 
designated area; and the provision of such a staging device wherein the 
staging device guides application of the mold and light energy to the 
cornea. 
Other objects, features and advantages of the invention shall become 
apparent as the description thereof proceeds when considered in connection 
with the accompanying illustrative drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
In accordance with the present invention, there is provided an improved 
method for accelerated orthokeratology. The improved method generally 
includes the three separate steps of: (1) softening the cornea so that the 
cornea can be shaped from a first configuration to a second emmetropic 
configuration; (2) reshaping the cornea by applying a mold to the cornea; 
and (3) restabilizing the corneal tissues so that they remain in their new 
configuration. 
Referring to FIGS. 15-17, the cornea 10 is made up of 5 distinct layers of 
tissues, namely the epithelium, Bowman's Membrane, stroma, Descemet's 
Membrane, and the endothelium. In FIGS. 15 and 17, it is obvious that the 
thickest layer of the cornea 10 is the stroma 16. The stroma is comprised 
of alternating lamellae of collagenous tissue (about 200-250 in number), 
the planes of which are parallel to the surface of the cornea. Referring 
to FIG. 16, the lamellae are each composed of fine collagen fibrils and 
proteoglycans. The collagen fibrils of alternate lamellae make a right 
angle with each other. Each lamellae crosses the whole of the cornea, 
being about 2 .mu.m thick. In the methods to be described herein, chemical 
agents which soften, degrade or "destabilize" the structural components of 
the stroma are topically administered to the cornea 10. The words soften, 
degrade, and destabilize are interchangeable for purposes of this 
specification, and they are all intended to denote a change in the corneal 
tissues which results in the cornea 10 becoming softer and more pliable so 
that the cornea can be reshaped from its' normal configuration to a second 
"emmetropic" configuration very quickly. 
Chemical and/or Enzymatic Softening Agents 
For purposes of the present invention, any one of a wide variety of 
chemical and/or enzymatic softening agents can be utilized to soften the 
corneal tissues. As previously described in the background, the Neefe U.S. 
Pat. Nos. 3,760,807, 3,776,230 and 3,831,604 collectively describe the use 
of chemicals such as proparacaine hydrochloride, dyclonine hydrochloride, 
chlorine in solution, and the use of proteolytic enzymes all to soften to 
cornea for reshaping. As also described previously herein, the U.S. 
patents to Harris describe the use of enzymes, such as hyalurodinase, for 
softening of the corneal tissues. Even further still, the Kelman and 
DeVore U.S. Pat. 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 of 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 recited 
therein are not intended to be limiting. 
Despite the multitude of different chemicals which could be utilized as 
destabilizing agents, the preferred families of destabilizing agents 
include anhydrides, acid chlorides, sulfonyl chlorides and sulfonic acids. 
The following lists of chemicals are intended to be representative of 
these types of chemicals, and are not intended to be limiting. 
Suitable, but non-limiting examples of potential anhydrides include: 
Dichloroacetic Anhydride; Diglycolic Anhydride; Chlorodifluoroacetic 
Anhydride; Dichloroacetic Anhydride; Acetic Anhydride; Dichloromaleic 
Anhydride; Maleic Anhydride; Acetic Anhydride; Trichloroacetic Anhydride; 
Chloroacetic Anhydride; Acetic Anhydride; Succinic-D4 Anhydride; 
Chloroacetic Anhydride; Dimethyl Pyrocarbonate; (Acetic Anhydride)-D6; 
Iodoacetic Anhydride; Hexafluoroglutaric Anhydride; Trifluoroacetic 
Anhydride; Succinic Anhydride; 3-Chloro-Glutaric Anhydride; Bromomaleic 
Anhydride; Succinic Anhydride; Citraconic Anhydride; 2,3-Dimethylmaleic 
Anhydride; Diethyl Pyrocarbonate; Itaconic Anhydride; 
CIS-1,2-Cyclobutanedicarboxylic Anhydride; 3,4-Pyridinedicarboxylic 
Anhydride; Glutaric Anhydride; S-Acetylmercaptosuccinic Anhydride; 
1-Cyclopentene-1,2-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; 
3-Methylglutaric Anhydride; 3,3-Dimethylglutaric Anhydride; 
(s)-(-)-2-(Trifluoroacetamido)succinic Anhydride; Propionic Anhydride; 
Tetrabromophthalic Anhydride; CIS-Aconitic Anhydride; Propionic Anhydride; 
Tetrachlorophthalic Anhydride; 6-Chloroisatoic Anhydride; Isatoic 
Anhydride; Heptafluorobutyric Anhydride; 5-Nitroisatoic Anhydride; 
EXO-3,6-Eposy, 1,2,3,6-Tetrahydrophthalic Anhydride; 4,5-Dichlorophthalic 
Anhydride; 6-Nitorisatoic Anhydride; CIS-1,2,3,6-Tetrahydrophthalic 
Anhydride; 3,6-Dichlorophthalic Anhydride; Phthalic Anhydride; 
3-Cyclohexene-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-Cyclobutanetetracarboxylic 
Dianhydride; (+)-Diacetyl-L-Tartaric Anhydride; 5-Chloroisatoic Anhydride; 
Tetrahydrofuran-2,3,4,5-Tetracarboxylic Dianhydride; 
CIS-1,2-Cyclohexanedicarboxylic Anhydride; Isobutyric Anhydride; 
3-Methoxyphthalic Anhydride; Crotonic Anhydride; Butyric Anhydride; 
2-Bromo-5-Norbornene-2,3-Dicarboxylic Anhydride; 
(+/-)-Trans-1,2-Cyclohexanedicarboxylic Anhydride; 
1,4,5,6,7,7-Hexachloro-5-Norbornene-2,3-Dicarboxylic Anhydride; 
3-Amino-5-Chloro-N-Methylisatoic Anhydride; Methacrylic Anhydride; 
Trimellitic Anhydride Chloride; N-Methylisatoic Anhydride; 
(+/-)-Isobutenylsuccinic Anhydride; 1,2,4-Benzenetricarboxylic Anhydride; 
CIS-5-Norbornene-Endo-2,3-Dicarboxylic Anhydride; 
1,2-Cyclohexanedicarboxylic Anhydride; 1-Methyl-6-Nitroisatoic Anhydride; 
3,5-Diacetyltetrahydropyran-2,4,6-Trione; 3-Ethyl-3-Methylglutaric 
Anhydride; Homophthalic Anhydride; 4-Methyl-1,2,3,6-Tetrahydrophthalic 
Anhydride; Butyric Anhydride; 4-Methylphthalic Anhydride; 
5-Methyl-3A,4,7,7A-Tetrahydrophthalic Anhydride; 2-Furoic Anhydride; 
3,6-Dimethyl-4-Cyclohexene-1,2-Dicarboxylic Anhydride; 
Norbornance-2,3-Dicarboxylic Anhydride; 2-Cyonoacetyl 
N-(4-Fluorophenyl)Carbamate; Endo-3,6,Dimethyl-3,6-Endoxohexahydrophthalic 
Anhydride; 3,6-Encoso-3-Methylhexahydrophthalic Anhydride; 2-Cyanoacetyl 
N-Phenylcarbamate; 2-Methyl-8-Oxaspiro(4.5)Decane-7,9-Dione; 
(+/-)-Hexahydro-4-Methylphthalic Anhydride; 3,6-Dimethylphthalic 
Anhydride; 8-Methyl-2-Oxaspiro(4.5)Decane-1,3-Dione; 
3,3-Tetramethyleneglutaric Anhydride; 
Bicyclo(2.2.2)Octa-2,5-Diene-2,3-Dicarboxylic Anhydride; 
3-Methoxy-5-Methylhexahydrophthalic Anhydride; 
1,2,4,5-Benzenetetracarboxylic Di-Anhydride; 
Endo-Bicyclo(2.2.2)Oct-5-Ene-2,3-Dicarboxylic Anhydride; Trimethylacetic 
Anhydride; 1,2,4,5-Benzenetetracarboxylic Dianhydride; 
methyl-5-Norbornene-2,3-Dicarboxylic Anhydride; Valeric Anhydride; 
2-Cyanoacetyl N-(2,3-Dichlorophenyl)Carbamate; Ethylenediaminetetraacetic 
Dianhydride; (S)-(+)-2-Methylbutyric Anhydride; 2-Phenylglutaric 
Anhydride; 1,8-Naphthalic Anhydride; Isovaleric Anhydride; 
2-Benzylsuccinic Anhydride; 2,3-Naphthalic Anhydride; Di-Tert-Butyl 
Dicarbonate; 
4,7-Dihydro-4,7A,7B-Trimethyl-4,7-Epoxyisobenzofuran-1,3(7A,7B)-Dione; 
4-Mercapto-1,8,Naphthalic Anhydride; Di-Tert-Butyl Dicarbonate; 
3-(Tert-Butyldimethylsilyoxy)Glutaric; 4-Sulfo-1,8-Naphthalic Anhydride; 
Di-Tert-Butyl Dicarbonate; 4-Bromo-1,8-Naphthalic Anhydride; 
4-Amino-1,8-Naphthalic Anhydride; 2-Cyanocetyl N-(P-Tolyl)Carbamate; 
4-Chloro-1,8-Naphthalic Anhydride; 2-Phthalimidosuccinic Anhydride; 
2-Cyanoacetyl N-(4-Methoxyphenyl)Carbamate; 4-Nitro-1,8-Naphthalic 
Anhydride; 4-Amino-3,6-Disulfo 1,8-Naphthalic Anhydride; 2-Cyanocetyl 
N-(3-Methoxyphenyl)Carbamamte; 3-Nitro-1,8-Naphthalic Anhydride; 
Bicyclo(2.2.2)Oct-7-Ene-2,3,5,6-Tetracarboxylic Dianhydride; 
Hexachlorohexahydro-1,4-Methanonaphthalene-6,7-Dicarboxylic Anhydride; 
Diphenic Anhydride; 2-(4-Acetoxyphenyl)Succinic Anhydride; 
N-Phthaloyl-Dl-Glutamic Anhydride; 
4-methylfuro(3',4':5,6)Naphtho(2,3-D)(1,3)Dioxole-1,3(1H,3H)-Dione; 
Carbobenzyloxy-L-Aspartic Anhydride; Carbobenzyloxy-L-Glutamic Anhydride; 
5-Bromo-1,2,3,4-Tetrahydro-1,4-Ethenonaphthalene-2,3-Dicarboxylic 
Anhydride; Bicyclo(4.2.2)Dec-7-Ene-9,10-Dicarboxylic Anhydride; 
9-Isopropyl-3-Oxaspiro(5.5)Undecane-2,4-Dione; 
5-Nitro-1,2,3,4-Tetrahydro-1,4-Ethenonaphthalene-2,3-Dicarboxylic 
Anhydride; 
3-((Ethoxycarbonyl)oxycarbonyl))-2,2,5,5-Tetramethyl-3-Pyrrolin-1-Yloxy, 
FR; 1,4,5,8-Naphthalenetetracarboxylic Dianhydride; 
5-Nitro-10-Oxo-1,2,3,4-Tetrahydro-1,4-Ethanonaphthalene2,3dicarboxylic 
Anhydride; 2-(1-Octenyl)Succinic Anhydride; BIS(2,6-Dichlorobenzoic 
Anhydride; Benzoic Anhydride; 
3-Methoxy-1,2,3,6-Tetrahydro-5-(Trimethylsilyoxy)phthalic Anhydride; 
4-Bromobenzoic Anhydride; 4-(2-Hydroxyethylthio)-1,8-Naphthalic Anhydride; 
Hexanoic Anhydride; 3,5-Dinitrobenzoyl N-(2-Chlorophenyl)Carbamate; and 
Diethylenetriaminepentaacetic Dianhydride 
Suitable, but non-limiting examples of potential acid chlorides include: 
Propionyl Chloride; Methacryloyl Chloride; Acryloyl Chloride; 
Methoxyacetyl Chloride; Methacryloyl Chloride; Methyloxalyl Chloride; 
Heptafluorobutyrl Chloride; Cyclopropanecarbonyl Chloride; 2,3 
Dichloropropionyl Chloride; 4,4,4-Trifluorocrotonyl Chloride; 
3-Bromopropionyl Chloride; Fumaryl Chloride; Acetoxyacetyl Chloride; 
(=/-)-2-Bromopropionyl Chloride; 4,4,4-Trifluorobutyrl Chloride; Ethyl 
Oxalyl Chloride; 2-Chloropropionyl Chloride; 4-Bromobutyrl Chloride; 
3-Chloropropionyl Chloride; Crotonyl Chloride; 4-Chlorobutyrl Chloride; 
5-(Chlorocarbonyl)Uracil; Ethyl Malonyl Chloride; 4-Chlorobutyrl Chloride; 
2-Thiophenecarbonyl Chloride; 3-Carbomethoxypropionyl Chloride; Butyrl 
Chloride; 2-Furoyl Chloride; 3,3-Dichloropivaloyl Chloride; Isobutyrl 
Chloride; Itaconyl Chloride; 2,2-Bis(Chloromethyl)Propionyl Chloride; 
Butyryl Chloride; Blutaryl Dichloride; 5-Bromovaleryl Chloride; Butyryl 
Chloride; 3,3-Dimethylacryloyl Chloride; 4-Morpholinecarbonyl Chloride; 
Cyclobutanecarbonyl Chloride; 5-Chlorovaleryl Chloride; 5-Nitro-2-Furoyl 
Chloride; 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-Ethylbutyrl 
Chloride; 3,4-Dichloro-2,5-Thiophenedicarbonyl Chloride; Ethylsuccinyl 
Chloride; Benzoyl-D5 Chloride; Nicontinoyl Chloride Hydrochloride; 
1-Chlorocarbonyl-1-Methylethyl Acetate; Pentafluorobenzoyl Chloride; 
Isonicotinoyl Chloride Hydrochloride; Methyl 4-(Chloroformyl)Butyrate; 
Pentachlorobenzoyl Chloride; 2-Thiopheneacetyl Chloride; 6-Bromohexanoyl 
Chloride; 2,3,4,5-Tetrafluorobenzoyl 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-Tridobenzoyl Chloride; 2,3-Difluorobenzoyl 
Chloride; 2-Bromobenzoyl Chloride; 2,4-Dichloro-5-Fluorobenzoyl Chloride; 
3,5-Dinitorbenzoyl Chloride; 4-Bromobenzoyl Chloride; 
2,4,6-Trichloribenzoyl Chloride; 2,6-Pyridnedicarbony Dichloride; 
4-Fluorobenzoyl Chloride; 2,6-Difluorobenzoyl Chloride; 
2,4-Dichlorobenzoyl Chloride; 2-Flurobenzyol 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 
Chlorde, 01.M Solution in Dichloromethane; 3-(Fluorosulfonyl)Benzoyl 
Chloride; 4-Chlorobenzoyl Chloride; 3-(2-Furyl)Alany Chloride 
Hydrochloride; 4-(Fluorosulfonyl)Benzoyl Chloride; 3-Chlorobenzoyl 
Chloride; Diethylmalonyl Dichloride; 2-lodobenzoyl Chloride; Benzoyl 
Chloride; 3-Methyladipoyl Chloride; 4-Iodobenzoyl Chloride; Benzoyl 
Chloride; Pimeloyl Chloride; 4-Nitrobenzoyl Chloride; Benzoyl-Carbonyl-13C 
Chloride; 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-Toluoyl Chloride; Pentafluorophenylacetyl Chloride; Phthaloyl 
Dichloride; Meta-Toluoyl Chloride; 4-(Trifluoromethly)Benzoyl Chloride; 
1,4-Phenylene BIS(Chloroformate); Pheylacetyl 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 chlorides include 
4-Chlorobenzenesulfonyl Chloride; 
4-Chloro-3-(Chlorosulfonyl)-5-Nitrobenzoic Acid; 
3-Fluorosulfonylbenzenesulfonyl Chloride; 4-Chlorobenzenesulfonyl 
Chloride; 3-(Fluorosulfonyl)benzoyl Chloride; 
4-Fluorosulfonylbenzenesuofonyl Chloride; 
4-Amino-6-Chloro-1,3-Benzenedisulfonyl Chloride; 4-(Fluorosulfonyl)benzoyl 
Chloride; O-Fluorosulfonylbenzenesulfonyl Chloride; 
3-Amino-4-Chlorobenzenesulfonyl; 2-Chloro-5-(Fluorosulfonyl)-Benzoic Acid; 
Pipsyl Chloride; Benzenesulfonyl Chloride; 4-(Chlorosulfonyl)phenyl 
Isocyanate; 4-Nitrobenzenesulfonyl Chloride; Benzenesulfonyl 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)Benzene-Sulfonyl Chloride; 
3-(Chlorosulfonyl)-Benzoic Acid; Methyl 2-(Chlorosulfonyl)benzoate; 
8-Quinolinesulfonyl Chloride; Alpha-Toluenesulfonyl Chloride; 
3-(Chlorosulfonyl)-P-Anisic Acid; 
4-(2,2-Dichlorocyclopropyl)-Benzenesulfonyl Chloride; P-Toluenesulfonyl 
Chloride; N-Acetylsulfanilyl Chloride; 2,4-Mesitylenedisulfonyl Chloride; 
O-Toluenesulfonyl Chloride; 2,5-Dimethoxy-4-Nitrobenzenesulfonyl Chloride; 
2-Mesitylenesulfonyl Chloride; P-Toluenesulfonyl Chloride; 
4-Dimethylamino-3-Nitrobenzenesulfonyl Chloride; 
6-Diazo-5,6-Dihyrdo-5-Oxo-1-Naphthalenesulfonyl Chloride; 
4-Methoxybenzenesulfonyl Chloride; 2,5-Dimethylbenzenesulfonyl Chloride; 
2,6-Naphthalenedisulfonyl Chloride; 3,5-Dicarboxybenzenesulfonyl Chloride; 
2,5-Dimethoxybenzenesulfonyl Chloride; 2-Naphthalenesulfonyl Chloride; 
Beta-Styrenesulfonyl Chloride; 5-Methylsulfonyl-Ortho-Toluenesulfonyl 
Chloride; 1-Naphthalenesulfonyl Chloride; 2,8,-Dibenzofurandisulfonyl 
Chloride; 4-(Dimethyllamino)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 Fluoride; 
(+)-10-Camphosulfonyl Chloride; 4,4'-Oxybis(Benzenesulfonyl Chloride); 
4-Chloro-6-Fluorosulfonyl-2-(4-Nitrophenyl)quinoline; 
(-)-10-Camphorsulfonyl Chloride; 4-(Phenylazo)Benzenesulfonyl Chloride; 
4-Chloro-2-Phenylquinoline-4',6-Disulfonyl Fluoride; 
(+/-)-10-Camphorsulfonyl Chloride; Dansyl Chloride; 
4-Chloro-2-Phenyl-6-Quinolinesulfonyl Fluoride; 
1-Chloro-4-Fluorosulfonyl-2-Naphthoyl chloride; 
4,4'-Methylenebis(Benzenesulfonyl Chloride); 
2,4,6-Triisopropylbenzenesulfonyl Chloride; Pentamethylbenzenesulfonyl 
Chloride; 2-(Chlorosulfonyl)Anthraquinone; 
4-Chloro-2-M-Tolyl)-6-Quinolinesolfonyl Fluoride; 
4-Chloro-6-Fluorosulfonyl-2-(4-Ethoxy-3-Methoxyphenyl)Quinolin; 
5-(Chlorosulfonyl)-2-(Hexadecycloxy)Benzoic Acid; 
4-Chloro-2-({-Tolyl)-6-Quinolinesulfonyl Fluoride; 
5,7,7-Trimethyl-2-(1,3,3-Trimethlbutyl)-1-Octancesulfonyl Chloride; 
3-Chlorosulfonyl-4-Hexadecycloxybenzoic Acid; 
5-Benzoyloxy-1-(3-Chlorosulfonylphenyl)-3-Methylpyrazole; 
4-Chloro-2(4-(N,N-Diethylaminosulfonyl)-Phenyl)-6-Quinolinesulfonyl 
Fluoride; 5-(Chlorosulfonyl)-2-(Hexadecyclsulfonyl)Benzoic Acid; 
1-Hexadecanesulfonyl Chloride; 
2-(4-Benzyloxyphenyl)-4-Chloro-6-Quinolinesulfonyl Fluoride; Methyl 
3-Chlorosulfonyl-4-(Hexadecyloxy)Benzoate; 
3-(4-Chlorophenylcarbamoyl)-4-Hydroxy-1-Naphthalenesulfonyl Fluoride; 
4-(Hexadecyloxy)Benzenesulfonyl Chloride; 
3-Nitro-4-(Octadecylamino)Benzenesulfonyl Chloride; Methyl 
4-(4-Chloro-6-Fluorosulfonyl-2-Quinolyl)Benzoate; 
4-(2,5-Dichlorophenylazo)-4-Fluorosulfonyl-1-Hydroxy-2-Naphthanilide; 
4-(4-Chloro-5,7-Dimethyl-2-Quinolyl)-Benzenesulfonyl Fluoride; 
5-Fluorosulfonyl-2-(Hexadecyloxy)Benzoyl Chloride; Ethyl 
4-Chloro-2-(4-Fluorosulfonylphenyl)-6-Quinolinecarboxylate; 
5-Chlorosulfonyl-2-(Hexadecylsulfonyl)Benzoyl Chloride; Oxalyl Chloride; 
Acetly-2-13C Chloride; Chlorocarbonylsulfenyl Chloride; Trichloroacetyl 
Chloride; Acetyl-1-13C 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 Cichloride; Oxalyl Chloride; Acetyl Chloride; and 
2,3-Dibromopropionyl Chloride. 
Suitable, but non-limiting examples of potential sulfonyl acids include 
4,6-Diamino-2-Methylthiopyrimidine-5-Sulfonic Acid; 
4-Pyridylhydroxymethanesulfonic Aceid; Sulfoacetic Acid, Pyridine Complex; 
3,3-Oxetanebis(Methanesulfonic Acid)Disodium Salt; 
2,5-Dimethyl-3-Thiophenesulfonic Acid Sodium Salt; 2-Pyrimidinesulfonic 
Acid, Sodium Sale; 1-Fluoropyridinium Triflate; Mes Monohydrate; 
2-Thiophenesulfonic Acid, Sodium Salt; 3-Sulfoisonicotinic Acid, Barium 
Salt; 3-Sulfobenzoic Acid; 
(+/-)-1-Hyrdoxy-2,5-Dioxo-3-Pyrrolidine-Sulfonic Acid, Monosodium Salt; 
(1-Methylpyridinium 3-Sulfonate); 6-Acetamido-3-Pyridinesulfonic Acid; 
5-Formyl-2-Furansulfonic Acid; 5-Methyl-3-Pyridinesulfonic Acid; 
4-Pyridineethanesulfonic Acid; 3-Pyridinesulfonic Acid; 
2-Pyridylhydorxymethanesulfonic Acid; 2-Pyridineethanesulfonic Acid; 
3-Pyridinesulfonic Acid, Sodium Salt; 3-Pyridylhydroxymethanesulffonic 
Acid; Isonicotinic Acid 2-(Sulfomethyl)-Hydrazide, Calcium Salt Dihyrdate; 
Hepes; 1-(2,5-Dichloro-4-Sulfophenyl)-5-Pyrazolone-3-Carboxylic Acid; Mops 
(4-Morpholinepropanesulfonic Acid); Hepes, Sodium Salt; 
5-Oxo-1-(4-Sulfophenyl)-2-Pyrazoline-3-Carboxylic Acid; Mops. Sodium Salt, 
Monohyrdate, (4-Morpholinepropanesulfonic Acid); Pipes 
(1,4-Piperazinebis-(Ethanesulfonic Acid)); 
5-Oxo-1-(4-Sulfophenyl)-2-Pyrazoline-3-Carboxylic Acid, Lead Salt; Mopso, 
(Beta-Hyroxy-4-Morpholine-Propanesulfonic Acid); Pipes, Disodium Salt 
Monohyrdate; 4-Chloro-3-(3-Methly-5-Oxo-2-Pyrazolin-1-Yl)-Benzesulfonic 
Acid; 1-Allylpyridinium 3-Sulfonte; 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; Ethyl 2-Sulfobenzoate, Sodium Sale; 
3-(5-Imino-3-Methyl-2-Pyrazolin-1-YL)Benzenesulfonic Acid; 
2-Pyridinealdoxime Methyl Methanke-Sulfonate; 
2-Methyl-1-(3-Sulfopropyl)Pyridinium Hydroxide, Inner Salt; Pyridinium 
3-Nitrobenzenesulfonate; 1-Piperidinepropanesulfonic Acid; Epps 
(4-(2-Hyrdoxyethyl)-1-Piperazine-Propanesulfonic Acid); 
2-Ethyl-5-Phenylisoxazolium 3'-Sulfonate; 
1-Ethyl-2-Methly-3-(3-Sulfopropyl)Benzimidazole; Acid Orange 74; 
2-Ethyl-5-Phenylisoxazolium 4'-Sulfonate Monohydrate; 
4-(5-Hyroxy-1-Phenyl-1,2,3-Trizol-4-Ylozo)Benzenesulfonic Acid, Sodium 
Salt; Tartrazine; Pyridinium P-Toluenesulfonate; 1,4-Dimethylpyridinium 
P-Toluenesulfonate; Acid Yellow 34; Methanesulfonic 
(4-Aminophenyl-SulfopropylThizdiasol-2-In-5-Ylidene)Hydrazide; 
4-Hyroxy-2-Phenyl-6-Quinolinesulfonic Acid; Mordant Red 19; 
4,5-Dihyrdoxy-3-(2-Thiazolylazo)-2,7-Naphthalenedisulfonic Acid, Sodium 
Salt; 3-Methoxycarbonyl-1-Methylpyridinium Para-Toluenesulfonate; 
1-Phenyl-3-(3-Sulfobenzamido)-2-Pyrazolin-5-One, Barium Salt; 
N-(4-Chlorobenzylideneamino)-Sulfanilic Acid, Pyridinium Salt; 
3-(2-Pyridyl)-5,6-Bis(5-Sulfo-2-Furyl)-1,2,4-Triazine Dina Salt/3H20; 
Flavazin L; 2-Fluoro-1-Methylpyridinium P-Toluene-Sulfonate; Acid Red 183; 
5-Tridecyl-1,2-Oxathiolane-2,2-Dioxide; 
N-Antipyrinyl-N-Methylaminomethanesulfonic Acid, Sodium Salt Monohydrate; 
Acid Yellow 17; 
4-((4-Chlorobenzylidene)-3-Methly-1-(4-Sulfophenyl)-2-Pyrazolin-5-One; 
Reatcie Blue 4; Cibacron Brilliant Yellos 3GP; 2-(3-Sulfobenzoyl)Pyridine 
2-Pyridyl-Hydrazone Dihyrdate; Acid Yellow 40; 
2-5,6-Bix-4-Sulfophenyl-1,2,4-Triazin-3-YL-4-Sulfophenyl 
Pyridine/3NA/Ind.Grad.; 
4-(1-Benzyl-5-Oxo-2-Pyrazolin-3-Ylcarbamoyl)Benzenesulfonic Acid, Barium 
Salt; 
(Bis)(Cyanoethyl)AminoBenzylidne)-Oxo-Sulfophenyl-Pyrazoline-Carboxylic 
Acid, NA; 1,1'Ethylenedipyridinium Di-P-Toluenesulfonate; 
2,6-Diamino-3-(4-(2-Diethylaminoethoxy)-Phenylazo)Pyridine 
Methanesulfonate; Acid Yellow 76; Merocyanine 540; Palatine Fast Yellow 
Bln; Acid Yellow 25; 1-Hexadecanesulfonic (Fluorophenyl) 
(Sulfopropyl)Thiadiazol-2-Ylidene)Hydrazide; 
3-(2-Pyridyl)-5,6-Diphenyl-1,2,4-Triazine-P,P'-Disulfonic Acid, 1-NA XH20; 
2-Hexadecylthio-5-Sulfobenzoic Acid, Pyridine Salt; Reative Blue 2; 
5-Phenyl-3-(4-Phenyl-2-Pyridyl)-1,2,4-Triazine-P,P'-Disulfonic Acid, 2NA 
Salt; Trans-4-(4-Dibutylamino)Styryl)-1-(3-Sulfopropyl)Pyr Oh/Inner Salt 
H2O; 1-Octadecylpyridinium P-Toluenesulfonate; Acid Yellow 29; 
4-(5-Oxo-3-Pentadecyl-2-Pyrazolin-1-Yl)Benzenesulfonic Acid, Sodium Salt; 
Direct Orange 31; Sephadex-Sp-C-50, Ion Exchange Resin; 
4-(4-(2-Hexadecyloxyphenyl)-5-Oxo-2-Pyrazolin-1-Yl)Benzenesulfonic Acid 
Sodium; Acid Yellow 42; Carboxy-Hexadecyloxybenzenesulfonic 
Methyl-Sulfophenyl-Thiadiazolinylidenehydraz; 
2,4-Bis(5,6(4-Sulfophenyl)-1,2,4-Triazine-3-Yl)Pyridine 4NA Salt H2O; Acid 
Orange 63; Reaactive Blue 15; Sephadex-Sp-C-25, Ion-Exchange Resin; 
8-Quinolinesulfonic Acid; 8-Ethoxy-5-Quinolinesulfonic Acid, Sodium Salt 
Hydrate; 2-Mercaptobenzothiazole-5-Sulfonic Acid, Sodium Salt; 
8-Hydroxyquinoline-5-Sulfonic Acid Monohydrate; 
8-Ethoxy-5-Quinolinesulfonic Acid; Benzothiazole-2,5-Disulfonic Acid; 
N-(Methylsulfonyloxy)-Phthalimide; 
6-Methoxy-3-(3-Sulfopropyl)-3H-Benzothiazolin-2-One Hydrazone; 
2-Benzofuransolfonic Acid; 1,3-Dioxo-2-Isoindoleneethanesulfonic Acid, 
Potassium Salt; 4-Sulfo-1,8-Naphthalic Anhydride, Potassium Salt, Tech.; 
2-Methylthio-5-Benzothiazolesulfonic Acid; Indole-3-Acetaldeyde Sodium 
Bisulfite Addition Compound; 8-Bromo-2-Dibenzo-Furansulfonic Acid, Sodium 
Salt; 2-Methylthiobenzimidazolesulfonic Acid; 
3-Methyl-2-Methylthio-6-Nitro-5-Sulfobenzothiazolium Methyl Sulfate; 
8-(Chloromercuri)-2-Dibenzofuransulfonic Acid, Sodium Salt; 
2-(3-Methly-2-Benzothiazolinyidene)-1-Hydrazinesulfonic Acid; 
8=Sulfo-2,4-Quinolinedicarboxylic Acid; 8-Nitro-2-Dibenzofuransulfonic 
Acid; 8-Hyroxy-7-Iodo-5-Quinoliinesulfonic Acid; 6-Norharmansulfonic Acid; 
4-Amino-3,6-Disulfo-1,8-Naphthalic Anhydride Dipotassium Salt; 
Harman-N-Sulfonic Acid; Indigo Carmine, Certified; 4-Dibenzofuransulfonic 
Acid, Sodium Salt Monohyrdate; 4-(2-Benzimidazolyl)-Benzenesulfonic Acid; 
Potassium Indigotrisulfonate; 2-Dibenzofuransulfonic Acid; Lucifer Yellow 
CH, Dipotassium Salt; Potassium Indigotetrasulfonate; 
2-Dibenzofuransulfonic Acid, Sodium Salt; Lucifer Yellow CH; 
7-Anilino-1-Naphthol-3-Sulfonic Acid; 2,8-Dibenzofurandisulfinic Acid, 
Disodium salt; Harmine-N-Sulfonic Acid, Sodium Salt; 
2,3-Dimethyl-6-Nitrobenzothiazolium Para-Toluenesulfonate; 
4,6-Dibenzofurandisulfonic Acid; 
3-(3-Sulfooxypropyl)-2,5,6-Trimethylbenzothiasolium Hydroxide, Inner Salt; 
3-Methly-2-(Methylthio)Benzothizolium P-Toluenesulfonate); 
2,8,Dibenzofurandisulfonic Acid, Disodium Salt; 
1-Ethyl-2-Methly-3-(3-Sulfooxypropyl)-Benzimidazolium Hydroxide, Inner 
Salt; Methanesulfonic Acid 
(1-Methly-2-Phenyl-6-Sulfo-4(1H)-Quinolyidene)Hydrazide; 
2-Sulfothianthrene-5,5,10,10-Tetraoxide, Sodium Salt; 
4-(4-Quinolylazo)Benzenesulfonic Acid; and 2-(Methylthio)Benzothiazole 
Ethyl P-Toluenesulfonate. All of the chemicals listed above are available 
from Aldrich Chemical Company (Milwaukee, Wis.) 
Of the above listings, it is likely that the preferred processes will 
utilize a simple anhydride to soften the cornea, i.e. glutaric anhydride, 
succinic anhydride or maleic anhydride since each of these anhydrides 
hydrolyze into rather innocuous compounds. 
Apparatus for Application of the Chemical Agents to the Cornea 
Because it is desired to limit chemical exposure to only the corneal 
tissues 10 of the eye, a staging device generally indicated at 12 has been 
developed to limit the spreading of the liquid treatment solutions which 
will be topically applied to the cornea. Referring to FIGS. 2, 2A, and 2B, 
the staging device 12 is preferably cylindrical in shape having upper and 
lower ends, 14, 16 respectively, and is preferably manufactured from a 
plastic material by injection molding. However, the staging device 12 
could also be formed from metal or fiberglass or any other suitable 
material. The staging device 12 is preferably 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 noted 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 
upon which the staging device 12 will rest when in use. The side wall 18 
of the staging device 12 is preferably between 0.5-2.0 mm thick. The idea 
is for the staging device to sit directly on the limbic area to prevent 
leakage of the drug solutions beyond the treated surface of the cornea 10 
(See FIG. 9). The staging device 12 further preferably includes an annular 
elastomeric gasket 20 (FIG. 2B) which is received around the lower end 16 
of the staging device 12. The elastomeric gasket 20 can be formed from a 
variety of non-porous elastomeric materials, such as synthetic and natural 
rubbers, non-porous foams, closed cell sponge, etc. A downwardly facing 
portion 22 of the gasket 20 will engage with the surface of the limbic 
area 17 of the cornea 10 when positioned to form an annular seal with the 
surface of the cornea 10. It is contemplated that the lower edges 24 of 
the lower end 16 of the staging device 12 could be tapered slightly 
inwardly to better conform to the sloping surface of the cornea 10. 
Likewise, the downwardly facing surfaces 22 of the gasket 20 could also be 
tapered inwardly to provide a better fit against the surface of the 
cornea. 
The staging apparatus 12 will be used for drug delivery to the cornea 10 as 
well as to guide and position the molds during reshaping. All drugs or 
solutions used in the methods are administered into the inside of the 
staging apparatus 12 after placement onto the cornea 10 wherein the 
interface of the gasket 20 with the cornea surface seals off the leakage 
of the solution from inside the device 12. To rigidly position the staging 
device 12 onto the cornea 10, as well as to prevent rotation thereof, a 
biological sealant or glue (not shown) may be applied to the downwardly 
facing portion 22 of the gasket 20 to adhere the gasket 20 to the limbic 
area 17 of the cornea 10. Any of the presently known biological sealants 
or glues would be acceptable in this context. Once the staging device 12 
is in place, the gasket 20 forms a seal and prevents the leakage of 
solutions which are administered into the center of the staging device. In 
this manner, the solutions and drugs are applied only to the central area 
of the cornea 10 which is to be reshaped. 
Although the preferred embodiment of the staging apparatus 12 is 
cylindrical it is also contemplated that an alternate staging apparatus 
12A could have a wider diameter at the upper end 14 wherein the outer 
diameter thereof ranges from 15-35 mm (See FIG. 2C.) 
It is also contemplated that the staging device 12 will have exterior 
markings 26 (FIG. 2) which will allow proper rotational alignment of the 
staging device 12 with respect to the eye, and also proper rotational 
alignment of the mold within the staging device for correction of 
astigmatism errors. 
Removing Solutions from the Staging Device 
Since the staging device 12 will effectively retain all of the drug 
solutions within its interior, it will be necessary to selectively remove 
the solutions during the procedure. For example, it will be necessary to 
wash the cornea 10 with various buffer solutions, and to apply different 
drug solutions at different times during the procedure. For this purpose, 
the Applicants have developed a simple sponge absorbing device (FIG. 3) 
generally indicated at 28 comprising a planar disc 30 having a handle 
portion 32 extending outwardly from an upper side thereof. The disc 32 has 
an outer diameter which will allow insertion of the disc 32 into the 
interior of the staging device 12. An absorbent sponge material 34 is 
adhered to the lower side of the disc 30 so that the sponge material 34 
engages with the surface of the cornea 10 to absorb any solution within 
the staging device 12 (See also FIG. 10). 
Reshaping 
After the cornea 10 is treated with a chemical softening agent, a mold 
generally indicated at 36 of predetermined curvature and configuration is 
fitted into the staging device (See FIGS. 4-5, and 11-12). Turning 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 further having an opposing rear surface 40. The mold 
36 can be fabricated from any one of a variety of materials, including 
metal, glass, plastic, quartz, or epoxy materials. With regard to 
preferred materials for fabrication, and as will be described hereinafter 
in Example 1, the present preferred method for restabilizing the cornea 10 
after shaping is by means of exposure to UV light. It is thus preferred 
that the mold 36 be fabricated from a UV permeable plastic, such as 
polymethyl methacrylate. This plastic material can first be molded in a 
generic mold shape and then have the mold surface 38 cut to a 
predetermined shape by a lathe. 
The mold surface 38 is provided with a predetermined geometric 
configuration which, when engaged with the surface of the cornea 10, is 
intended to reshape the cornea to an emmetropic configuration. The 
specifics of the geometric curvature of various portions of the mold 
surface 38 will be discussed hereinafter. The mold surface 38 can be 
formed by any one of a variety of known methods for forming optical lenses 
such as lath cutting, molding or milling depending on the fabrication 
material of the mold 36. 
The rear surface 49 of the mold 36 is preferably provided with a key 42 so 
that the mold 36 can be properly rotationally oriented on the surface of 
the cornea 10. Rotation of the mold 36 can be accomplished by a holder 
tool generally indicated at 44 having a complementary detent 46 on the end 
thereof (FIGS. 6 and 6A). More specifically, the holder tool 44 has a 
hollow cylindrical body portion 48 which is intended to be inserted into 
the staging device to engage the mold 36 situated threin. The detent 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 finger grip 50 having a 
fluted outer surface 52 which can be easily grasped and rotated by the 
surgeon. The finger grip is also hollow to provide a continuous open 
through the tool holder 44. Referring to FIG. 7, holder 44 is shown in 
conjunction with the end of a light rod 54 which 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 which fits into the open end of the finger 
grip 50 of the holder tool 44. The light guide 54 is maintained in 
assembled relation with the holder tool 44 by means a set screw 58 which 
extends through the finger grip 50 and engages with the reduced diameter 
end 56 of the light guide 54. 
After the mold 36 is oriented in the staging device 12, downward pressure 
is applied to the mold 36 for a predetermined period of time (1-10 
minutes) to re-shape the softened cornea 10. Pressure is preferably 
applied by pressing downwardly on the holder tool 44 which is engaged with 
the mold 36 (See FIG. 12). 
Mold Configurations 
Various types of mold configurations can be used to treat different 
refractive errors of the eye. Hereinbelow, the Applicant's will discuss 
various mold configurations which can be utilized in the subject process. 
A. Residual Astigmatism (Internal Astigmatism) 
Internal astigmatism is the astigmatism in the eyes optical system other 
than that measured on the corneal surface. A patient with internal 
astigmatism will require a toric central curve mold application. When the 
spectacle refractive astigmatism equals the corneal astigmatism in a given 
median, the internal astigmatism is zero. This is to say that the total 
astigmatism of the eye is produced by the corneal toricity. Sphericalizing 
the cornea with a mold of the subject invention will result in zero 
refractive astigmatism. 
If the refractive astigmatism differs in magnitude but the same direction 
as the corneal toricity, the difference is the internal astigmatism. There 
are two cases. One where the corneal astigmatism is greater than the 
refractive astigmatism, where a bitoric mold would be used having its 
steeper curve aligned with the steeper corneal meridian. The resultant 
optical outcome would be an emmetropic with a toric cornea (the axis of 
corneal astigmatism would be the same pre-post procedure.) The other case 
would be a corneal astigmatism of less magnitude than the refractive 
astigmatism along the same meridian. The mold for treating this condition 
would have a bitoric central curve. Axis of astigmatism mold correction 
90.degree. from the refractive astigmatism axis. The mold would have a 
toric power equal to the difference between the power of the refraction 
and corneal astigmatism. The resultant optical outcome would be an 
emmetropic eye with a toric cornea. 
EXAMPLE A 
Corneal K's 44/46 at 90 (s diopter of corneal astigmatism) 
Spectacle refraction -300=-100.times.180 (1 diopter refractive astigmatism) 
Mold toricity -100.times.180 
EXAMPLE B 
Corneal k's 44/45 at 90 (1 diopter of stigmatism) 
Spectacle refraction -300=-200.times.180 (2 diopter of astigmatism) 
Mold toricity -100.times.90 
The visual optics are fundamental for those skilled in the art. The 
resultant internal astigmatism as defined by the formulas will be 
corrected for with a bitoric mold having an axis of myopic correction with 
the axis of residual myopic astigmatism. 
Where the axis of corneal astigmatism and the axis of spectacle refraction 
are not along the same meridian, a new bitoric mold axis and power can be 
determined by applying visual optics formulas known in the art. 
The spherical mold is fit flatter than the corneal astigmatic meridian by 
the magnitude of the spectacle refraction. The mold should have a power 
equal to the power of the flat corneal astigmatic meridian with a 
refractive power along that meridian. This method works only if there is 
no residual astigmatism. 
When a residual astigmatism exists, a bitoric mold is used which has a 
minus cylinder axis at the same axis as the residual astigmatism. The 
power difference between bitoric curves is equal to the magnitude of the 
residual astigmatism. The spherical component of the mold is determined by 
the aforementioned method. 
B. Spherical Base Curves for Mold Design 
The spherical mold is fit flatter than the flat corneal astigmatic meridian 
by the magnitude of the spectacle refraction along that flat meridian. The 
mold base curve should have a power equal to the power of the flat corneal 
astigmatic meridian minus the refractive power along that meridian. This 
method works only if there is no residual astigmatism. 
(1) Simple Myopia 
a. -300 sph spectacle refraction 
b. 44 sph corneal power 
c. 44-3=41 diopters=mold base curve power 
(2) Simple Astigmatism 
a. p1=-100.times.180 
b. 43/44 at 90 corneal powers 
c. 44 (flat corneal power)-plane (0)=44 diopter mold base curve power. The 
mold is aligned on the flat corneal meridian 
(3) Compound Myopic Astigmatism 
a. -200=-100.times.180 
b. 43/44 at 90 corneal powers 
c. 44-43=1 diopters=mold base curve power 
C. Base Curve Mold Configuration for Hyperopia, Compound Hyperopic 
Astigmatism, and Presbyopia are Computed Using the Same Formulas 
The base curve of the mold is steeper than the flat corneal meridian by the 
magnitude of the spectacle refraction along that flat corneal meridian. 
The base curve can be spherical or aspherical or bitoric and the optic 
zone diameter will vary depending on the magnitude of the power correction 
required. The mid-peripheral curve will be flatter, preferably aspherical, 
but may be spherical and will in general be flatter and wider as the 
central refractive power/corneal power ratio increases. This is to say 
that the more hyperopic refractive correction, the steeper the central 
base curve and the flatter the mid-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 optic zone 
(in myopes) and displacing the tissue laterally into the relief zone 
pocket, without changing the overall square mm surface area of the cornea. 
The overall configuration is a smooth spherical optic zone (unless a 
bitoric curve is necessary for residual astigmatism) with a gradual relief 
zone that gradually flattens out to the natural peripheral corneal 
curvature. 
Mold Dimensions 
Referring to FIGS. 5 and 8C, there is shown a mold configuration 36 of the 
general type which will be used in the processes of the present invention. 
The mold 36 is particularly suited for treating a myopic cornea wherein 
the object is to flatten out the central portion of the cornea 10. In this 
regard, the mold surface 38 includes a central curve zone 60, a single 
mid-peripheral (relief) curve 62, and a large base curve 64. The width of 
the central curve 60 is about 4 mm, and the width of the mid-peripheral 
(relief) curve 62 is between 1 mm and 1.5 mm, spherical or aspherical. The 
configuration of the base curve was discussed generally hereinabove. The 
mid-peripheral curve 62 is 2-15 diopters steeper than the central base 
curve 60 for myopic corrections. The larger the base curve/k relationship 
(increased myopia, the steeper and wider the mid-peripheral (relief) curve 
62. The same holds true for hyperopia wherein the rule is that the larger 
the base curve/k relationship, the flatter and wider the mid-peripheral 
curve 62. The mid-peripheral curve 62 in hyperopic molds are between 2-15 
diopters flatter than the central base curve 60. 
The type and magnitude of corneal astigmatism will influence the width and 
curvature of the mid-peripheral (relief) curve 62 in this and likely all 
mold designs. Larger magnitudes of compound hyperopic astigmatism (CHA) 
will require flatter and wider mid-peripheral curves and larger magnitudes 
of CMA will require steeper and wider relief mid-peripheral curves. Small 
degrees of total corneal astigmatism and small spherical emmetropics will 
require less of a difference in curvature between the central base curve 
and mid-peripheral relief curve. Aspheric mid-peripheral curves will 
optimally be used for astigmatic corneas with reverse geometry mold 
designs. If an outer peripheral curve is utilized 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 cornea alignment. 
Referring now to FIGS. 8A-8B, a mold 36A incorporating multiple 
mid-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 generaly hereinabove. The first mid-peripheral relief curve 68 
(innermost curve) has a diameter of 0.3 mm to about 4.0 mm. This curve is 
3-9 diopters steeper than the central optic zone 66. The second 
mid-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 nearer to the corneal alignment than the first 
mid-peripheral relief curve. The function of the peripheral curve 72 is to 
block the cornea from structural flow outside of the periphery of the mold 
36A. 
Referring now to FIG. 8D, a mold 36B for use in treating hyperopic and 
compound hyperopic astigmatism is illustrated. The mold 36B is first 
divided into two zone, a central optic zone 74, and a mid-peripheral zone 
generally indicated at 76. The mid-peripheral zone is divided into three 
separate curvatures areas, namely a transition zone 78, an apex 80 of the 
mid-peripheral curvature 76 and an outer curve portion 82. Generally 
speaking, the central optic zone 74 is steeper than the corneal curvature 
(spherical, aspherical or bitoric). The transition zone 78 is flatter than 
the optical zone 74, but not as flat as the apex zone 80. The apex 80 of 
the mid-peripheral curvature 76 bears on the corneal surface and may move 
laterally or medially on the curvature zone 76. The outer curve 82 is 
stepper than the apex area curve 80 and aligned more with the surface of 
the cornea 10. 
Referring to FIG. 8E, yet another mold configuration 36C is illustrated for 
use in treating myopia or mixed myopic astigmatism. The mold surface 38 is 
provided with a central optic curve zone 84, and a mid-peripheral relief 
zone generally indicated at 86. The central optic curve zone 84 can be 
spherical, aspherical or bitoric, and is approximately 6.0-10 mm is 
diameter, with an optimal diameter of about 7 mm. The relief zone 86 is 
preferably divided into three areas, namely, an inner portion 88, an apex 
portion 90 and outer peripheral portion 92. The mid-peripheral relief zone 
86 is a concave surface which is approximately 1.5-3.0 mm in width having 
a variable apex location within the curve 86. The inner portion 88 of the 
mid-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 skewed to 
medial or lateral locations 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 maybe steeper than the optical zone 84 and also steeper than the 
corneal curvature under the mold 36 at that location. The radius of 
curvature of each of the portions of the mid-peripheral relief zone 86 is 
off alignment with the line of sight. The preferred embodiment of the mold 
36C will not have an outer peripheral curve zone 92. 
All of the above-described mold information is of the general type known in 
the art of fitting orthokeratology contact lenses. The information has 
been provided as a means for explanation of the various molds used during 
the processes described, but it is not intended to limit the scope of the 
disclosure to any particular type or design of mold structure as many 
different mold design will work to produce the same effect of shaping the 
corneal tissues to the curvature of the mold to alter the refractive power 
of the eye. 
Stabilization of the Cornea After Shaping 
The last and most crucial step in the process comprises restabilizing the 
corneal tissues after reshaping into the new "emmetropic" configuration. 
For purposes of the present disclosure the Applicant has adopted the term 
"stabilizing agent" as a means to refer to all of the potential agents for 
restabilizing the collagen matrix of the eye. Included among the stabling 
agents to be described hereinafter are chemical stabilizing agents, light 
energy including UV and visible light, thermal radiation, microwave 
energy, and radio waves. 
Crosslinking Using UV Light 
It is well known that UV radiation and UVC is effective in crosslinking 
collagen. (See the to Kelman and DeVore U.S. Pat. Nos. 4,969,912; 
5,201,764; 5,219,895; 5,354,336; and 5,492,135 regarding UV crosslinking 
of collagen materials). While the exact mechanism is not well understood, 
it is thought that UVC acts primarily on tyrosine residues in the collagen 
molecule. Accordingly, the polymerization or crosslinking of the reshaped 
corneal tissues may be carried out simply by exposing the cornea to short 
wave UV light (e.g. 254 nm). However, the rate of polymerization is not 
practical for use because of the potential damage to the corneal tissues 
caused by long term exposures to UV light. The rate of polymerization may 
be significantly increased by applying appropriate redox initiators to the 
cornea prior to the UV light exposure. Without such an initiator, UV 
polymerization, would require at least 10 minutes of exposure. 
Suitable, but non-limiting, examples of some initiators include sodium 
persulfate, sodium thiosulfate, 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 
promoted the polymerization of the corneal matrix within between about 30 
seconds and about 2 minutes, preferably between about 30 second and 1 
minute, but insufficient to cause oxidative damage to the corneal tissues. 
Polymerization by UV irradiation may be accomplished in the short wave 
length range by using a standard 254 nm source of between about 4 and 12 
watts. Polymerization generally occurs in between about 30 seconds and 
about two minutes, preferably no longer than 1 minute, at an exposure 
distance of between about 1.5 and 5 cm distance. Because excess UV 
exposure will begin to depolymerize the collagen polymers ad cause eye 
damage, it is important to limit UV irradiation for short periods. At 254 
nm, the penetration depth is very limited. 
While short wave UV in the range of 254 nm is disclosed, it is to be 
understood that other wavelengths of UV would also be suitable depending 
on application of a suitable photoinitiator matched to the particular 
wavelength. In the experiments outlined below, the UV exposure was 
conducted with no filter, thereby providing broadband UV irradiation. 
Filters will provide a more specific wavelength, which will be matched to 
an appropriate photochemical or redox initiator. Filters also reduce the 
temperature elevation at the exposure site. Sodium persulfate which is 
listed as the preferred initiator in Example 1 exhibits a maximum 
absorption at 254 nm, but appears to be effective at much higher 
wavelengths. For maximum efficiency, it is preferred to match the UV 
wavelength to a specific redox or photochemical initiator. 
Gamma Irradiation 
Polymerization, or crosslinking, can also be accomplished using Gamma 
irradiation between 0.5 to 2.5 Mrads. However, excess Gamma exposure will 
also depolymerize collagen polymers. 
Chemical Crosslinking 
There are many potential chemical "stabilizing" agents for use in 
chemically cross-linking the collagen matrix. 
The historical collagen cross-linking technique utilizes glutaraldehyde. 
Glutaraldehyde and other aldehydes, such as glyoxal, acrolein, 
acetaldehyde, butyraldehyde, propionaldehyde, and formaldehyde create 
lateral bridges between polypeptide chains and between collagen fibers. 
Other suitable, but non-limiting, chemical cross-linkers include 
periodates, acyl azides, Denacol.RTM. ethers, i.e. Sorbitol Polyglycidyl 
Ether, Polyglycerol Polyglycidyl Ether, Pentaerythritol Polyglycidyl 
Ether, Diglycerol Polyglycidyl Ether, Triglycidyl Tris Isocyanurate and 
Glycerol Polyglycidyl Ether, bifunctional acylation agents, including 
anhydrides, acid chlorides, and sulfonyl chlorides, e.g. 
1,2,3,4-cyclobutanetetracarboxylic dianhydride, 
Tetrahydrofuran-2,3,4,5-tetracarboxylic dianhydride, 
1,2,4,5-benzenetetracarboxylic di-anhydride, ethylenediaminetetraacetic 
dianhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, 
glutaryl dichloride, adipoyl chloride, 3-methyladipoyl chloride, pimeloyl 
chloride, terephthaloyl chloride, isophthaloyol dichloride, phthaloyl 
dichloride, 1,4-phenylene bis(chloroformate), 2,4-mesitylenedisulfonyl 
chloride, 2,6 naphthalenedisulfonyl chloride, malonyl dichloride, and 
homobifunctional amine cross-reactive cross-linkers such as 
homobifunctional imidoesters and homobifunctional N-hydroxysuccinimidyl 
are also suitable. 
Unfortunately, many of these agent elicit adverse tissue reactions, and 
therefore their use must be carefully controlled and directed to a 
specific site. In this regard, chemical cross-linking is not discussed 
herein as the preferred method of stabilization. However, such agents 
would be highly useful in the present method should appropriate delivery 
systems become available in the future. 
Thermal Radiation 
Heat is another possible means of cross-linking, or "stabilizing" the 
corneal tissues after reshaping. It is generally known that the 
application of heat speeds up tissue metabolism and will help stabilize 
the tissue faster than if no heat were applied. Laser thermal keratoplasty 
(LTK) is the use of heat produced at specified points in the cornea stroma 
by absorption of laser light to modify the structure and mechanical 
properties of stromal collagen. Typically, in LTK, the laser is directed 
to a particular spot on the eye. As the spot absorbs light and heat up to 
about 55-60 degrees centigrade, the collagen will shrink. Rings of spots 
are used to tighten the tissues to create a change in the anterior 
curvature of the cornea. As a final step in the present methodology, the 
reshaped cornea could be exposed to laser light wherein the corneal 
tissues would be heated and stabilized in the new emmetropic 
configuration. The treatment parameters at this point in development are 
purely speculative. 
Microwave Energy 
Microwave energy is also currently being investigated as a means of 
treating 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. Campbell, Microwave 
Thermokeratoplasty, Investigational Ophthamology and Visual Science, 
36:s988, 1995, and D. X. Pang, B. S. Trembly, L. R. Bartholomew, and P. J. 
Hoopes, Microwave Thermokeratoplasty: Reshaping Corneal Contour (Corneal 
Microwave-TKP), Accepted for Publication, International Journal of 
Hyperkeratoplasty, (1998). See also U.S. Pat. No. 4,881,543 to Trembly 
entitled Combined Microwave Heating and Surface Cooling of the Cornea 
(1989), and U.S. Pat. No. 5,618,284 to Sand, Collagen Treatment Apparatus, 
(1997). The mechanism for cross-linking appears 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 speeds up 
tissue metabolism and will help stabilize the tissue faster than if no 
heat were applied. It is contemplated that 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 reshaped cornea could be exposed to 
microwave energy wherein the corneal tissues would be heated, either at 
specific points or throughout the whole cornea, and stabilized in the new 
emmetropic configuration. The treatment parameters at this point in 
development are purely speculative. 
Application of Heat Through the Mold 
Another possible technique of applying heat to the cornea would be through 
direct contact with the mold. In this regard, the mold could be provided 
with a controlled heating element to heat the mold body to a predetermined 
temperature. Such heating could be accomplished by electric elements or by 
a heated fluid flow through the mold. 
Radio Waves 
It is still further contemplated that radio frequency energy could be used 
to generate heat in the stroma to stabilize the coreal tissues after 
softening and molding as described in the present invention. As a final 
step in the present methodology, the reshaped cornea could be exposed to 
radio frequency (RF) energy wherein the corneal tissues would be heated, 
either at specific points or throughout the whole cornea, and stabilized 
in the new emmetropic configuration. The treatment parameters at this 
point in development are purely speculative. See U.S. Pat. No. 5,638,384 
to Gough et al entitled Multiple antenna ablation apparatus, (1997) 
describing the use of RF energy in surgical ablation techniques. 
Visible Light 
It is also possible to crosslink collagen using visible light. However, 
this method will require a photochemical initiator to transfer photoenergy 
into a free radical chemical reaction. Suitable, but non-limiting, 
photochemical dye initiators include Pheno-safranin, methyl red, 
bromphenol blue, crocein scarlet, phenol red, alcian blue, Rose Bengal, 
Methylene blue, A zure A, Toluidine blue, Eosin Y, Evans blue, Methylene 
green, Amythest violet, Lumazine, Thionine, Xanthopterin, 
2,3,5-triphenyl-tetrazolium Cl., Acridine red, Acridine orange, 
Proflavine, Rosazurin, Azure B, Bindschedler's green, Primuline, Acridine 
yellow, Neutral red, Erythrosine, Fluorescein, Indo-oxine, and Malachite 
green. Of these chromophores, Fluorescein, Eosin, Indo-oxine and Rose 
bengal appear to be best suited for corneal use. It is noted that the 
exposure times for these chromophores are excessive and therefore, the use 
of these chemical may not be practical in actual usage. However, use is 
being tested for optimum performance times. 
It is thought that Redox initiators will work much faster. Suitable but 
non-limiting, redox initiators include Diphenylamine, Erioglaucin A, 
2,2'-Dipyridyl ferrous ion, and N-Phenylanthranilic acid. 
Visible Light Stabilization Following Destabilization Using a Sulfonic Acid 
Chromophore 
An alternative technique for reshaping 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 specific 
wavelength of visible light corresponding to a maximum absorbance of the 
chromophore attached to amines reacted in the softening process. 
Suitable, but non-limiting sulfonic acid dyes include: lucifer yellow vs, 
direct yellow 8, 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), 
4,5-dihydroxy-3-(4-sulfo1napthylazo)27napthalenedisulfonic acid, 
2-dibenzofuransulfonic acid, 1-(2-hydroxyethyl)quinolinium 
p-toluenesulfonate, brilliant sulphaflavine, thiazine red r, pyrogallol 
red, papaverine sulfonic acid, direct yellow 27, napthylazoxine a, 
1-ethyl-2undecyl-5-benzamidazolesulfonic acid, hoechst 2495, 
8-hydroxy-7-(4-sulfo-1-napthylazo)-5-quinolinesulfonic acid, 
3-hydroxy-4(2-hydroxy-4-sulfo-1-napthyl-azo)-2-napthalenecarboxylic acid, 
1-hexadecanesulfonic (methyl-sulfo-benzothiazolinylidene)hydrazid, 
sulfobromophthalein sodium hydrate, prmulin, sulforhodamine g, 
8-hydroxy-5-(1-napthylazo)-2-naphthyalenesulfonic acid, 
2-methylthio-3-phenylbenzothiazolium para-toluenesulfonate, 
2-(m-aminophenyl)-1-dodecylbenzimidazole-5-sulfonic acid, 
2-(4-bromobenzyl)isothiothiouronium 
8-(4-hydroxy-1-naphthylazo)2naphthalenesulfonate, 
(hexadecyl-methylsulfamoyl)benzenesulfonic 
(me-sulfo-bz-thiazolinyliden)hydrazid, merocyanine 540, fast sulphon black 
f, 2-(3-amino-3-methylpentyl)-1-octadecyl-5-benzimidazolesulfonic acid, 
sulforhodamine b, 
3,6-bis-(4-solfo-1-naphthylazo)-4,5-di-oh-2,7-naphthyalenedisulfonic acid, 
copper phthalocyanine-3,4',4",4.sup.111 -tetrasulfonic acid, 
1-hexadecanesesulfonic acid, 4-(hexadecylsulfamoyl)bezenesulfonic acid, 
nickel phthalocyaninetetrasulfonic acid, azocarmine g, sulforhodamine 101 
hydrate, 
6,6'-(1,1'-biphenyl44'diylbisazo)bis(4amino5hydroxy13naphthalenedi-so3h2on 
a salt), azocarmine b, carboxy-hexadecyloxybenzenesulfonic acid, 
1-hexadecanesesulfonic acid, thiazol yellow g, 
carboxy-hexadecylsulfonylbenzenesulfonic acid, 1-hexadecanesesulfonic 
acid, chlorazol azurine, 3-methyl-2-benzothiazolinone azine, methylthymol 
blue, reactive blue 15, acetamidohexadecylsulfonylbenzenesulfonic acid, 
owens blue, direct yellow 29, indocyanine green 
EXAMPLE 1 
Preferred Methodology 
(1) Apply the staging apparatus 12 to the eye (FIG. 9); 
(2) Pretreat the cornea (10--shown in solid line) with 0.02M disodium 
phosphate buffer solution (94), pH 8.5 for 1 minute (FIG. 9); 
(3) Remove excess buffer (94) with the sponge apparatus (28) (See FIG. 10); 
(4) Treat cornea (10) with a solution containing 5-50 mg of glutaric 
anhydride dissolved immediately before application in 1 ml of 0.02M 
disodium phosphate, pH 8.5. The preferred concentration of glutaric 
anhydride is 10-30 mg pre ml of disodium phosphate; 
(5) Remove the anhydride solution with sponge apparatus; 
(6) Place a shaping mold (36) into the staging apparatus 12, rotate to the 
desired position using the tool holder 44, and apply appropriate pressure 
to attain the desired anterior curvature of the cornea (10) (See FIG. 12) 
(the original corneal shape is now shown in broken line and the new second 
configuration is shown in solid line); 
(7) With the mold 36 in place, treat the cornea with a Redox initiator in a 
slightly alkaline buffer. For sodium persulfate, preferably use 0.1M to 
0.5M sodium persulfate in 0.02M phosphate buffer pH 8.0. The preferred 
concentration of sodium persulfate is 0.2M to 0.4M; 
(8) With the mold 36 still in place, expose the corneal surface to UV 
irradiation in the 250-390 nm range. Preferably an EFOS Novacure unit is 
utilized and set at 3000 mW/cm.sup.2 for 10-120 seconds, preferably 30-60 
seconds. The EFOS light guide 96 is positioned within the staging 
apparatus 12 at a distance of 0.25-3.0 inches from the cornea, optimally 
0.25-1.0 inches. Exposures may range from 2500 mW.times.120 seconds to 
4500 mW.times.45 seconds, preferably 2500 mW.times.75 seconds to 4500 
mW.times.30 seconds (FIG. 13); 
(9) Following the UV exposure, the cornea is thoroughly washed with 0.02M 
phosphate buffer at pH 7.2; and 
(10) The mold 36 and staging apparatus 12 are then removed from the eye and 
the eye is examined using slit lamp and corneal topography methods to 
determine the degree of change of curvature and to determine if additional 
shaping may be required (FIG. 14). The original curvature of the cornea is 
shown in FIG. 14 in broken line, while the new "emmetropic" curvature is 
shown in solid line. 
Stabilization of Long Term Orthokeratology Patients 
One of the anticipated benefits of the stabilization process is that it can 
be used to stabilize the corneas of patients having already undergone long 
term orthokeratology. The stabilization procedures will eliminate the need 
to continue wearing retainer lenses to maintain the shape of the cornea. 
While it may be possible to simply utilize the stabilization step for 
these patients, it is anticipated that the cornea will have to be 
destabilized before it can be restabilized to take on the new 
configuration. In such a method, the eye would be destabilized using the 
methodology as described above. Because the eye was already preshaped, 
very little shaping will be necessary to reshape the eye to the proper 
configuration. A mold would however be used to maintain the proper shape 
during the restabilization process. With the mold in place, the eye would 
then be exposed to a photoinitiator and exposed to UV light to restabilize 
the cornea in the new configuration. 
Experiment 1 
Experiments conducted using enucleated pig eyes. Pre-treatment and 
post-treatment evaluations of eyes were made by slit-lamp examination and 
by taking K-readings. In a control portion of the experiment, several pig 
eyes were treated with contact lenses only. Neither destabilization nor 
stabilization were performed on the control eyes. As expected, there was 
no change in the corneal curvature as determined by slit-lamp examination 
and measurement of K-readings. In a second part of the experiment, contact 
lenses were applied to two eyes without destablization, followed by 
treatment with sodium persulfate solution (photochemical initiator) and 
exposure to UV light using an Ultracure 100SS Plus UV light source 
manufactured by EFOS of Williamsville, N.Y. The dosage of light was 
approximately 1500 mWatts for about 30 seconds (broad wavelength of 25-390 
nm). Pretreatment measurements of the two eyes were 36.75/37.5. After 
treatment measurements were 43/41.5 and 40.5/44. The eyes were clear and 
the ridge created by the contact lens was visible after 1 hour. In a third 
part of the experiment, an eye was treated with a pH 8.76 phosphate buffer 
for 1 minute followed by exposure to 10 mg/ml glutaric anhydride in 
phosphate buffer for 1 minute to destabilize the cornea. A contact lens 
was applied. The eye was then flushed with phosphate buffer, pH 7.2 to 
remove residual glutaric acid and then soaked with phosphate buffer 
(0.02M), pH 8.0 containing 0.3M sodium persulfate. UV light was applied 
for 20 seconds, the lens removed and the eye again flushed with phosphate 
buffer, pH 7.2. The pretreatment measurements of the eye were 36.75/37.5. 
The pig eye was examined after the glutaric anhydride treatment and 
measurements were 40.5/39.0. After UV treatment, measurements were too 
steep to read and rather distorted. Indentations and ridges created by the 
lens were observed immediately post-treatment and 1 hour after treatment. 
Results showed definite curvature changes and very obvious ridges created 
by the lens. 
Experiment 2 
Second set of experiments also using enucleated pig eyes. an EYESYS 
topographical system was available to perform topographical mapping of the 
eyes before and after treatment. In addition, the EFOS Ultracure 100SS was 
available for UV light treatment. In a control part of the experiment, an 
eye was examined using a slit lamp and using the EYESYS system. Neither 
glutaric anhydride nor sodium persulfate were administered prior to 
application of UV light exposure. However, buffers were administered to 
simulate full treatment. EYESYS evaluation demonstrated that the surface 
characteristics following treatment remained the same as before treatment. 
In a second part of the experiment, a second pig eye was examined by slit 
lamp, and EYESYS. Topographical profiles were printed. The eye was them 
soaked in phosphate buffer at pH 8.5 for 2 minutes. Glutaric anhydride at 
10 mg/ml was prepared in an alcohol 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 soaked in a sodium persulfate solution (0.3M 
sodium persulfate in pH 8.5 buffer) with the lens still in place. After 
several one (1) minute soaks in the sodium persulfate solution, the eye 
was exposed to UV light for about 30 seconds. The lens was removed and the 
eye washed with phosphate buffer, pH 7.2. The eye was then examined by 
slit lamp and EYESYS. Slit lamp examination showed that the eye had 
developed some cloudiness (probably due to the alcohol solution containing 
the glutaric anhydride). EYESYS examination demonstrated that the eye 
topography had been changed. In a third part of the experiment, a third 
eye was treated the same as above, expect that the glutaric anhydride was 
delivered in a phosphate buffer, pH 8.5, in an attempt to prevent the 
clouding observed using alcohol. Slit lamp examinations showed much less 
corneal clouding. EYESYS examinations demonstrated topographical changes 
appearing to match the curvature of the applied contact lens. The 
experiments show that the described techniques could alter the shape of 
the anterior curvature of the cornea. 
Experiment 3 
Third set of experiments using a live rabbit. Both the EYESYS topographical 
system and EFOS Ultracure 100SS were available. The rabbit's eyes were 
examined by slit-lamp and EYESYS. Topographical profiles were printed. The 
control eye was left untreated. The experimental eye was exposed to 0.02M 
phosphate buffer, pH 8.5, and treated with glutaric anhydride at 20 mg/ml 
in pH 8.5 phosphate buffer followed by application of a contact lens. The 
eye was then washed with 0.02M phosphate buffer, pH 8.5 to remove residual 
glutaric acid, soaked with buffer containing 0.3M sodium persulfate and 
exposed to UV light for two 30 second bursts with the contact lens in 
place. Both the control and treated eyes were examined by slit-lamp and 
EYESYS. Topographical profiles were printed. The treated eye showed and 
obvious change in surface topography. Slit-lamp examination indicated some 
corneal haze, which cleared in about 1 hour. The experiment, in a live 
animal, demonstrated that the anterior corneal curvature could be altered 
in a live subject using the described techniques. 
It can therefore be seen that the instant invention provides a unique and 
effective method for quickly modifying the anterior curvature of the 
cornea with non-invasive surgical techniques. The three step process of 
destabilizing, shaping and restabilizing will allow potential patients to 
have the refractive vision errors corrected in a matter of hours, without 
a recovery period, rather than endure the lengthy and oftentimes painful 
procedures which currently exist. The unique method of restabilizing the 
cornea significantly decreases treatment time, and stabilizes the cornea 
in a corrected emmetropic configuration that will eliminate the need for 
retainer lenses or any other corrective lenses for that matter. As stated 
above, the unique aspects of the method are believed to reside in the 
unique three steps, destabilization, reshaping and stabilization and in 
the apparatus used to achieve the method. There has not been provided in 
the art 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, the instant 
invention is believed to represent a significant advancement in the art 
which has substantial commercial merit. 
While there is shown and described herein certain specific structure 
embodying the invention, it will be manifest to those skilled in the art 
that various modifications and rearrangements of the parts may be made 
without departing from the spirit and scope of the underlying inventive 
concept and that the same is not limited to the particular forms herein 
shown and described except insofar as indicated by the scope of the 
appended claims.