Using the light adjustable lens (LAL) to increase the depth of focus by inducing targeted amounts of asphericity
10874505 ยท 2020-12-29
Assignee
Inventors
Cpc classification
B29C35/00
PERFORMING OPERATIONS; TRANSPORTING
C08J2383/07
CHEMISTRY; METALLURGY
C08G77/20
CHEMISTRY; METALLURGY
C08L83/00
CHEMISTRY; METALLURGY
C08L83/00
CHEMISTRY; METALLURGY
A61F2/1637
HUMAN NECESSITIES
C08J3/28
CHEMISTRY; METALLURGY
C08J2383/06
CHEMISTRY; METALLURGY
International classification
B29D11/00
PERFORMING OPERATIONS; TRANSPORTING
B29C35/00
PERFORMING OPERATIONS; TRANSPORTING
C08J3/28
CHEMISTRY; METALLURGY
Abstract
In general, the present invention relates to optical elements, which can be modified post-manufacture such that different versions of the element will have different optical properties. In particular, the present invention relates to lenses, such as intraocular lenses, which can be converted into aspheric lenses post-fabrication. Also, the present invention relates to a method for forming aspheric lenses post-fabrication.
Claims
1. An aspheric lens comprising: a first polymer matrix; and a modifying composition, dispersed in the first polymer matrix, and polymerized into a second polymer matrix interspersed within the first polymer matrix; wherein the aspheric lens is not a multifocal lens, and a wavefront of the aspheric lens at a 4 mm measurement aperture has a 4.sup.th order spherical aberration in a range of (+0.194 m, 0.385 m).
2. The aspheric lens of claim 1, wherein the first polymer matrix is one of a polyacrylate, a polymethacrylate, a polyvinyl, a polysiloxane, a polyphosphazenes and copolymers of thereof.
3. The aspheric lens of claim 2, wherein the polysiloxane is a polydimethylsiloxane.
4. The aspheric lens of claim 3, wherein the polydimethylsiloxane has at least one of the formulas: ##STR00029## wherein m, n, x and y each separately represents an integer having a value between 1 and 10,000.
5. The aspheric lens of claim 1, wherein the first polymer matrix is formed in the presence of a crosslinker.
6. The aspheric lens of claim 5, wherein the crosslinker has the formula: ##STR00030## wherein n represents an integer having a value between 1 and 10,000.
7. The aspheric lens of claim 1, wherein the modifying composition has at least one of the formulas: ##STR00031## wherein n and x each separately represents an integer having a value between 1 and 10,000, ##STR00032## wherein n and x each separately represents an integer having a value between 1 and 10,000, ##STR00033## wherein m and n each separately represents an integer having a value between 1 and 10,000, and ##STR00034## wherein m, and n each separately represents an integer having a value between 1 and 10,000.
8. The aspheric lens of claim 7, wherein the modifying composition has the formula ##STR00035## wherein n and x each separately represents an integer having a value between 1 and 10,000.
9. The aspheric lens of claim 2, wherein the polyacrylate is one of a polyalkyl acrylates, a polyhydroxyalkyl acrylate and a combination thereof.
10. The aspheric lens of claim 2, wherein the polymethacrylate is one of a polymethyl methacrylate, a polyhydroxyethyl methacrylate, a polyhydroxypropyl methacrylate and a mixture thereof.
11. The aspheric lens of claim 2, wherein the polyvinyl is one of a polystyrene, a polyvinylpyrrolidone and mixtures thereof.
12. The aspheric lens of claim 1, wherein: the 4.sup.th order spherical aberration of the wavefront of the aspheric lens is in the range of (0.006 m, 0.385 m).
13. The aspheric lens of claim 1, wherein: the 4.sup.th order spherical aberration of the wavefront of the aspheric lens is in the range of (0.194 m, 0 m).
14. The aspheric lens of claim 1, wherein: the aspheric lens, upon implantation into an eye, causes a total measured 4.sup.th order spherical aberration over a 4 mm pupil in the eye in the range of (0.10 m, 0.23 m).
15. The aspheric lens of claim 1, wherein: the aspheric lens, upon implantation into an eye, causes a total measured 4.sup.th order spherical aberration over a 4 mm pupil in the eye in the range of (0.04 m, 0.10 m).
16. The aspheric lens of claim 1, wherein: the 4.sup.th order spherical aberration is a Z(12) type aberration.
17. The aspheric lens of claim 1, wherein: a defocus of the aspheric lens is 1 Dioptre.
18. The aspheric lens of claim 1, wherein: a magnitude of a 6.sup.th order aberration of the wavefront of the aspheric lens at a 4 mm measurement aperture is smaller than 0.04 m.
19. The aspheric lens of claim 18, wherein: the magnitude of the 6.sup.th order aberration of the wavefront of the aspheric lens is smaller than 0.01 m.
20. The aspheric lens of claim 1, the modifying composition comprising: one of a monomer and a macromer, with an endcap that includes a photopolymerizable group that facilitated the stimulus-induced polymerization.
21. The aspheric lens of claim 20, comprising: a photoinitiator that initiated a photopolymerization of the photopolymerizable group.
22. The aspheric lens of claim 1, wherein: the modifying compound is polymerized by stimulus-induced polymerization into a second polymer matrix.
23. The aspheric lens of claim 1, wherein: a 6.sup.th order aberration of the wavefront of the aspheric lens at a 4 mm measurement aperture is in a range of (0 m, 0.04 m).
24. The aspheric lens of claim 1, further comprising: a photoinitiator.
25. The aspheric lens of claim 1, the modifying composition comprising: a group that was capable of photopolymerization before the modifying composition was polymerized.
26. The aspheric lens of claim 1, wherein: the 4.sup.th order spherical aberration of the wavefront of the aspheric lens is in the range of (0.106 m, 0.385 m).
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) For a more complete understanding of the present invention, reference is now made to the following descriptions taken in conjunction with the accompanying drawing.
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DETAILED DESCRIPTION OF THE INVENTION
(14) As used herein the specification, a or an may mean one or more. As used herein in the claim(s), when used in conjunction with the word comprising, the words a or an may mean one or more than one. As used herein another may mean at least a second or more. Furthermore, as used herein, the terms comprise, have and include are open-ended linking verbs. Any forms or tenses of one or more of these verbs, such as comprises, comprising, has, having, includes and including, are also open-ended. For example, any method that comprises, has or includes one or more steps is not limited to possessing only those one or more steps and also covers other unlisted steps.
(15) Throughout this application, the term about is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the experimental test articles.
(16) Chemical Group Definitions
(17) When used in the context of a chemical group, hydrogen means H; hydroxy means OH; oxo means O; halo means independently F, Cl, Br or I; amino means NH.sub.2 (see below for definitions of groups containing the term amino, e.g., alkylamino); hydroxyamino means NHOH; nitro means NO.sub.2; imino means NH (see below for definitions of groups containing the term imino, e.g., alkylimino); cyano means CN; isocyanate means NCO; azido means N.sub.3; in a monovalent context phosphate means OP(O)(OH).sub.2 or a deprotonated form thereof; in a divalent context phosphate means OP(O)(OH)O or a deprotonated form thereof; mercapto means SH; and thio means S
(18) In the context of chemical formulas, the symbol means a single bond, means a double bond, and means triple bond. The symbol ---- represents an optional bond, which if present is either single or double. The symbol represents a single bond or a double bond. Thus, for example, the structure
(19) ##STR00001##
includes the structures
(20) ##STR00002##
(21) As will be understood by a person of skill in the art, no one such ring atom forms part of more than one double bond. The symbol , when drawn perpendicularly across a bond indicates a point of attachment of the group. It is noted that the point of attachment is typically only identified in this manner for larger groups in order to assist the reader in rapidly and unambiguously identifying a point of attachment. The symbol
means a single bond where the group attached to the thick end of the wedge is out of the page. The symbol
means a single bond where the group attached to the thick end of the wedge is into the page. The symbol
means a single bond where the conformation (e.g., either R or S) or the geometry is undefined (e.g., either E or Z).
(22) Any undefined valency on an atom of a structure shown in this application implicitly represents a hydrogen atom bonded to the atom. When a group R is depicted as a floating group on a ring system, for example, in the formula:
(23) ##STR00003##
(24) then R may replace any hydrogen atom attached to any of the ring atoms, including a depicted, implied, or expressly defined hydrogen, so long as a stable structure is formed. When a group R is depicted as a floating group on a fused ring system, as for example in the formula:
(25) ##STR00004##
(26) then R may replace any hydrogen attached to any of the ring atoms of either of the fused rings unless specified otherwise. Replaceable hydrogens include depicted hydrogens (e.g., the hydrogen attached to the nitrogen in the formula above), implied hydrogens (e.g., a hydrogen of the formula above that is not shown but understood to be present), expressly defined hydrogens, and optional hydrogens whose presence depends on the identity of a ring atom (e.g., a hydrogen attached to group X, when X equals CH), so long as a stable structure is formed. In the example depicted, R may reside on either the 5-membered or the 6-membered ring of the fused ring system. In the formula above, the subscript letter y immediately following the group R enclosed in parentheses, represents a numeric variable. Unless specified otherwise, this variable can be 0, 1, 2, or any integer greater than 2, only limited by the maximum number of replaceable hydrogen atoms of the ring or ring system.
(27) For the groups and classes below, the following parenthetical subscripts further define the group/class as follows: (Cn) defines the exact number (n) of carbon atoms in the group/class. (Cn) defines the maximum number (n) of carbon atoms that can be in the group/class, with the minimum number as small as possible for the group in question, e.g., it is understood that the minimum number of carbon atoms in the group alkenyl.sub.(C8) or the class alkene.sub.(C8) is two. For example, alkoxy.sub.(C10) designates those alkoxy groups having from 1 to 10 carbon atoms (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any range derivable therein (e.g., 3 to 10 carbon atoms). (Cn-n) defines both the minimum (n) and maximum number (n) of carbon atoms in the group. Similarly, alkyl.sub.(C2-10) designates those alkyl groups having from 2 to 10 carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any range derivable therein (e.g., 3 to 10 carbon atoms)).
(28) The term saturated as used herein means the compound or group so modified has no carbon-carbon double and no carbon-carbon triple bonds, except as noted below. The term does not preclude carbon-heteroatom multiple bonds, for example a carbon oxygen double bond or a carbon nitrogen double bond. Moreover, it does not preclude a carbon-carbon double bond that may occur as part of keto-enol tautomerism or imine/enamine tautomerism.
(29) The term aliphatic when used without the substituted modifier signifies that the compound/group so modified is an acyclic or cyclic, but non-aromatic hydrocarbon compound or group. In aliphatic compounds/groups, the carbon atoms can be joined together in straight chains, branched chains, or non-aromatic rings (alicyclic). Aliphatic compounds/groups can be saturated, that is joined by single bonds (alkanes/alkyl), or unsaturated, with one or more double bonds (alkenes/alkenyl) or with one or more triple bonds (alkynes/alkynyl). When the term aliphatic is used without the substituted modifier only carbon and hydrogen atoms are present. When the term is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2.
(30) The term alkyl when used without the substituted modifier refers to a monovalent saturated aliphatic group with a carbon atom as the point of attachment, a linear or branched, cyclo, cyclic or acyclic structure, and no atoms other than carbon and hydrogen. Thus, as used herein cycloalkyl is a subset of alkyl. The groups CH.sub.3 (Me), CH.sub.2CH.sub.3 (Et), CH.sub.2CH.sub.2CH.sub.3 (n-Pr), CH(CH.sub.3).sub.2 (iso-Pr), CH(CH.sub.2).sub.2 (cyclopropyl), CH.sub.2CH.sub.2CH.sub.2CH.sub.3 (n-Bu), CH(CH.sub.3)CH.sub.2CH.sub.3 (sec-butyl), CH.sub.2CH(CH.sub.3).sub.2 (iso-butyl), C(CH.sub.3).sub.3 (tert-butyl), CH.sub.2C(CH.sub.3).sub.3 (neo-pentyl), cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexylmethyl are non-limiting examples of alkyl groups. The term alkanediyl when used without the substituted modifier refers to a divalent saturated aliphatic group, with one or two saturated carbon atom(s) as the point(s) of attachment, a linear or branched, cyclo, cyclic or acyclic structure, no carbon-carbon double or triple bonds, and no atoms other than carbon and hydrogen. The groups, CH.sub.2 (methylene), CH.sub.2CH.sub.2, CH.sub.2C(CH.sub.3).sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, and
(31) ##STR00005##
are non-limiting examples of alkanediyl groups. The term alkylidene when used without the substituted modifier refers to the divalent group CRR in which R and R are independently hydrogen, alkyl, or R and R are taken together to represent an alkanediyl having at least two carbon atoms. Non-limiting examples of alkylidene groups include: CH.sub.2, CH(CH.sub.2CH.sub.3), and C(CH.sub.3).sub.2. When any of these terms is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. The following groups are non-limiting examples of substituted alkyl groups: CH.sub.2OH, CH.sub.2Cl, CF.sub.3, CH.sub.2CN, CH.sub.2C(O)OH, CH.sub.2C(O)OCH.sub.3, CH.sub.2C(O)NH.sub.2, CH.sub.2C(O)CH.sub.3, CH.sub.2OCH.sub.3, CH.sub.2OC(O)CH.sub.3, CH.sub.2NH.sub.2, CH.sub.2N(CH.sub.3).sub.2, and CH.sub.2CH.sub.2Cl. The term haloalkyl is a subset of substituted alkyl, in which one or more hydrogen has been substituted with a halo group and no other atoms aside from carbon, hydrogen and halogen are present. The group, CH.sub.2Cl is a non-limiting examples of a haloalkyl. An alkane refers to the compound HR, wherein R is alkyl. The term fluoroalkyl is a subset of substituted alkyl, in which one or more hydrogen has been substituted with a fluoro group and no other atoms aside from carbon, hydrogen and fluorine are present. The groups, CH.sub.2F, CF.sub.3, and CH.sub.2CF.sub.3 are non-limiting examples of fluoroalkyl groups. An alkane refers to the compound HR, wherein R is alkyl.
(32) The term alkenyl when used without the substituted modifier refers to an monovalent unsaturated aliphatic group with a carbon atom as the point of attachment, a linear or branched, cyclo, cyclic or acyclic structure, at least one nonaromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other than carbon and hydrogen. Non-limiting examples of alkenyl groups include: CHCH.sub.2 (vinyl), CHCHCH.sub.3, CHCHCH.sub.2CH.sub.3, CH.sub.2CHCH.sub.2 (allyl), CH.sub.2CHCHCH.sub.3, and CHCHC.sub.6H.sub.5. The term alkenediyl when used without the substituted modifier refers to a divalent unsaturated aliphatic group, with two carbon atoms as points of attachment, a linear or branched, cyclo, cyclic or acyclic structure, at least one nonaromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other than carbon and hydrogen. The groups, CHCH, CHC(CH.sub.3)CH.sub.2, CHCHCH.sub.2, and
(33) ##STR00006##
are non-limiting examples of alkenediyl groups. When these terms are used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. The groups, CHCHF, CHCHCl and CHCHBr, are non-limiting examples of substituted alkenyl groups. An alkene refers to the compound HR, wherein R is alkenyl.
(34) The term alkynyl when used without the substituted modifier refers to an monovalent unsaturated aliphatic group with a carbon atom as the point of attachment, a linear or branched, cyclo, cyclic or acyclic structure, at least one carbon-carbon triple bond, and no atoms other than carbon and hydrogen. As used herein, the term alkynyl does not preclude the presence of one or more non-aromatic carbon-carbon double bonds. The groups, CCH, CCCH.sub.3, and CH.sub.2CCCH.sub.3, are non-limiting examples of alkynyl groups. The term alkynediyl when used without the substituted modifier refers to a divalent unsaturated aliphatic group, with two carbon atoms as points of attachment, a linear or branched, cyclo, cyclic or acyclic structure, at least one carbon-carbon triple bond, and no atoms other than carbon and hydrogen. When these terms are used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. An alkyne refers to the compound HR, wherein R is alkynyl.
(35) The term aryl when used without the substituted modifier refers to a monovalent unsaturated aromatic group with an aromatic carbon atom as the point of attachment, said carbon atom forming part of a one or more six-membered aromatic ring structure, wherein the ring atoms are all carbon, and wherein the group consists of no atoms other than carbon and hydrogen. If more than one ring is present, the rings may be fused or unfused. As used herein, the term does not preclude the presence of one or more alkyl group (carbon number limitation permitting) attached to the first aromatic ring or any additional aromatic ring present. Non-limiting examples of aryl groups include phenyl (Ph), methylphenyl, (dimethyl)phenyl, C.sub.6H.sub.4CH.sub.2CH.sub.3 (ethylphenyl), naphthyl, and the monovalent group derived from biphenyl. The term arenediyl when used without the substituted modifier refers to a divalent aromatic group, with two aromatic carbon atoms as points of attachment, said carbon atoms forming part of one or more six-membered aromatic ring structure(s) wherein the ring atoms are all carbon, and wherein the monovalent group consists of no atoms other than carbon and hydrogen. As used herein, the term does not preclude the presence of one or more alkyl group (carbon number limitation permitting) attached to the first aromatic ring or any additional aromatic ring present. If more than one ring is present, the rings may be fused or unfused. Non-limiting examples of arenediyl groups include:
(36) ##STR00007##
(37) When these terms are used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. An arene refers to the compound HR, wherein R is aryl.
(38) The term aralkyl when used without the substituted modifier refers to the monovalent group -alkanediyl-aryl, in which the terms alkanediyl and aryl are each used in a manner consistent with the definitions provided above. Non-limiting examples of aralkyls are: phenylmethyl (benzyl, Bn) and 2-phenyl-ethyl. When the term is used with the substituted modifier one or more hydrogen atom from the alkanediyl and/or the aryl has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. Non-limiting examples of substituted aralkyls are: (3-chlorophenyl)-methyl, and 2-chloro-2-phenyl-eth-1-yl.
(39) The term heteroaryl when used without the substituted modifier refers to a monovalent aromatic group with an aromatic carbon atom or nitrogen atom as the point of attachment, said carbon atom or nitrogen atom forming part of an aromatic ring structure wherein at least one of the ring atoms is nitrogen, oxygen or sulfur, and wherein the group consists of no atoms other than carbon, hydrogen, aromatic nitrogen, aromatic oxygen and aromatic sulfur. As used herein, the term does not preclude the presence of one or more alkyl group (carbon number limitation permitting) attached to the aromatic ring or any additional aromatic ring present. Non-limiting examples of heteroaryl groups include furanyl, imidazolyl, indolyl, indazolyl (Im), methylpyridyl, oxazolyl, pyridyl, pyrrolyl, pyrimidyl, pyrazinyl, quinolyl, quinazolyl, quinoxalinyl, thienyl, and triazinyl. The term heteroarenediyl when used without the substituted modifier refers to an divalent aromatic group, with two aromatic carbon atoms, two aromatic nitrogen atoms, or one aromatic carbon atom and one aromatic nitrogen atom as the two points of attachment, said atoms forming part of one or more aromatic ring structure(s) wherein at least one of the ring atoms is nitrogen, oxygen or sulfur, and wherein the divalent group consists of no atoms other than carbon, hydrogen, aromatic nitrogen, aromatic oxygen and aromatic sulfur. As used herein, the term does not preclude the presence of one or more alkyl group (carbon number limitation permitting) attached to the first aromatic ring or any additional aromatic ring present. If more than one ring is present, the rings may be fused or unfused. Non-limiting examples of heteroarenediyl groups include:
(40) ##STR00008##
(41) When these terms are used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2.
(42) The term acyl when used without the substituted modifier refers to the group C(O)R, in which R is a hydrogen, alkyl, aryl, aralkyl or heteroaryl, as those terms are defined above. The groups, CHO, C(O)CH.sub.3 (acetyl, Ac), C(O)CH.sub.2CH.sub.3, C(O)CH.sub.2CH.sub.2CH.sub.3, C(O)CH(CH.sub.3).sub.2, C(O)CH(CH.sub.2).sub.2, C(O)C.sub.6H.sub.5, C(O)C.sub.6H.sub.4CH.sub.3, C(O)CH.sub.2C.sub.6H.sub.5, C(O)(imidazolyl) are non-limiting examples of acyl groups. A thioacyl is defined in an analogous manner, except that the oxygen atom of the group C(O)R has been replaced with a sulfur atom, C(S)R. When either of these terms are used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. The groups, C(O)CH.sub.2CF.sub.3, CO.sub.2H (carboxyl), CO.sub.2CH.sub.3 (methylcarboxyl), CO.sub.2CH.sub.2CH.sub.3, C(O)NH.sub.2 (carbamoyl), and CON(CH.sub.3).sub.2, are non-limiting examples of substituted acyl groups.
(43) The term alkoxy when used without the substituted modifier refers to the group OR, in which R is an alkyl, as that term is defined above. Non-limiting examples of alkoxy groups include: OCH.sub.3, OCH.sub.2CH.sub.3, OCH.sub.2CH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH(CH.sub.2).sub.2, O-cyclopentyl, and O-cyclohexyl. The terms alkenyloxy, alkynyloxy, aryloxy, aralkoxy, heteroaryloxy, and acyloxy, when used without the substituted modifier, refers to groups, defined as OR, in which R is alkenyl, alkynyl, aryl, aralkyl, heteroaryl, and acyl, respectively. Similarly, the term alkylthio when used without the substituted modifier refers to the group SR, in which R is an alkyl, as that term is defined above. When any of these terms is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. The term alcohol corresponds to an alkane, as defined above, wherein at least one of the hydrogen atoms has been replaced with a hydroxy group.
(44) The term alkylamino when used without the substituted modifier refers to the group NHR, in which R is an alkyl, as that term is defined above. Non-limiting examples of alkylamino groups include: NHCH.sub.3 and NHCH.sub.2CH.sub.3. The term dialkylamino when used without the substituted modifier refers to the group NRR, in which R and R can be the same or different alkyl groups, or R and R can be taken together to represent an alkanediyl. Non-limiting examples of dialkylamino groups include: N(CH.sub.3).sub.2, N(CH.sub.3)(CH.sub.2CH.sub.3), and N-pyrrolidinyl. The terms alkoxyamino, alkenylamino, alkynylamino, arylamino, aralkylamino, heteroarylamino, and alkylsulfonylamino when used without the substituted modifier, refers to groups, defined as NHR, in which R is alkoxy, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, and alkylsulfonyl, respectively. A non-limiting example of an arylamino group is NHC.sub.6H.sub.5. The term amido (acylamino), when used without the substituted modifier, refers to the group NHR, in which R is acyl, as that term is defined above. A non-limiting example of an amido group is NHC(O)CH.sub.3. The term alkylimino when used without the substituted modifier refers to the divalent group NR, in which R is an alkyl, as that term is defined above. When any of these terms is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2. The groups NHC(O)OCH.sub.3 and NHC(O)NHCH.sub.3 are non-limiting examples of substituted amido groups.
(45) The term alkylphosphate when used without the substituted modifier refers to the group OP(O)(OH)(OR), in which R is an alkyl, as that term is defined above. Non-limiting examples of alkylphosphate groups include: OP(O)(OH)(OMe) and OP(O)(OH)(OEt). The term dialkylphosphate when used without the substituted modifier refers to the group OP(O)(OR)(OR'), in which R and R can be the same or different alkyl groups, or R and R can be taken together to represent an alkanediyl. Non-limiting examples of dialkylphosphate groups include: OP(O)(OMe).sub.2, OP(O)(OEt)(OMe) and OP(O)(OEt).sub.2. When any of these terms is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2.
(46) The terms alkylsulfonyl and alkylsulfinyl when used without the substituted modifier refers to the groups S(O).sub.2R and S(O)R, respectively, in which R is an alkyl, as that term is defined above. The terms alkenylsulfonyl, alkynylsulfonyl, arylsulfonyl, aralkylsulfonyl, and heteroarylsulfonyl, are defined in an analogous manner. When any of these terms is used with the substituted modifier one or more hydrogen atom has been independently replaced by OH, F, Cl, Br, I, NH.sub.2, NO.sub.2, CO.sub.2H, CO.sub.2CH.sub.3, CN, SH, OCH.sub.3, OCH.sub.2CH.sub.3, C(O)CH.sub.3, N(CH.sub.3).sub.2, C(O)NH.sub.2, OC(O)CH.sub.3, or S(O).sub.2NH.sub.2.
(47) The term effective, as that term is used in the specification and/or claims, means adequate to accomplish a desired, expected, or intended result. Effective amount, or Therapeutically effective amount when used in the context of treating a patient or subject with a stimulus means that the amount of the stimulus which, when administered to a subject or patient for treating a condition, is sufficient to effect such treatment for the condition.
(48) As used herein, the term patient or subject refers to a living mammalian organism, such as a human, monkey, cow, sheep, goat, dog, cat, mouse, rat, guinea pig, or transgenic species thereof. In certain embodiments, the patient or subject is a primate. Non-limiting examples of human subjects are adults, juveniles, infants and fetuses.
(49) As generally used herein pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues, organs, and/or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio.
(50) A repeat unit is the simplest structural entity of certain materials, for example, frameworks and/or polymers, whether organic, inorganic or metal-organic. In the case of a polymer chain, repeat units are linked together successively along the chain, like the beads of a necklace. For example, in polyethylene, [CH.sub.2CH.sub.2], the repeat unit is CH.sub.2CH.sub.2. The subscript n denotes the degree of polymerization, that is, the number of repeat units linked together. When the value for n is left undefined or where n is absent, it simply designates repetition of the formula within the brackets as well as the polymeric nature of the material. The concept of a repeat unit applies equally to where the connectivity between the repeat units extends three dimensionally, such as in, modified polymers, thermosetting polymers, etc.
(51) Treatment or treating includes (1) inhibiting a disease in a subject or patient experiencing or displaying the pathology or symptomatology of the disease (e.g., arresting further development of the pathology and/or symptomatology), (2) ameliorating a disease in a subject or patient that is experiencing or displaying the pathology or symptomatology of the disease (e.g., reversing the pathology and/or symptomatology), and/or (3) effecting any measurable decrease in a disease in a subject or patient that is experiencing or displaying the pathology or symptomatology of the disease.
(52) The above definitions supersede any conflicting definition in any of the reference that is incorporated by reference herein. The fact that certain terms are defined, however, should not be considered as indicative that any term that is undefined is indefinite. Rather, all terms used are believed to describe the invention in terms such that one of ordinary skill can appreciate the scope and practice the present invention.
Compositions of the Invention
(53) Compositions of the present disclosure may be made using the methods described above and in Example 1 below. These methods can be further modified and optimized using the principles and techniques of organic chemistry and/or polymer chemistry as applied by a person skilled in the art. Such principles and techniques are taught, for example, in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (2007), and/or in R. J. Young & P. A. Lovell, Introduction to Polymers, (Chapman & Hall 1991), which are incorporated by reference herein.
Discussion of General Embodiments
(54) From a pure optical standpoint, the depth of focus (DOF) for an optical system (e.g. the eye) is simply defined as the maximum movement away from the ideal image plane, which may be made without causing a serious deterioration of the image. According to the Rayleigh limit, there will be no appreciable deterioration of the image, i.e., no marked change from the Airy pattern, provided the maximum phase difference between disturbances arriving at the center of the pattern, does not exceed /2. With reference to
(55)
(56) where AP represents a spherical wave converging to the image point B, is the wavelength, n is the refractive index in the image space, U is the slope of the refracted ray, and 1 is the DOF. Therefore, an optical system such as the human eye will have an inherent amount of depth of focus even for a perfectly imaging system.
(57) An additional property of optical systems that can be exploited to further increase the depth of focus, and therefore provide for both distance and near vision, is spherical aberration. In simple terms, spherical aberration is defined as the variation of focus with aperture.
(58) The presence of spherical aberration increases the depth of focus in the eye. In combination with a residual refractive error (defocus), an induced spherical aberration can be used to provide patients with good contrast images both for distance and near objects. The key issue is to determine the required values of both 4.sup.th order spherical aberration and defocus that provide good near vision without deteriorating the image quality for distance objects. An experimental approach that permits determination of the optimum values of spherical aberration and defocus is an adaptive optics visual simulator. (Fernandez et al., 2002). An example of this type of instrument is shown in
(59) The spherical IOL of the present invention is capable of post-fabrication alteration of optical properties. The lens is self-contained and does not require the addition or removal of materials to change the optical properties. Instead, the optical properties of the lens are altered by exposing a portion or portions of the lens to an external stimulus which induces polymerization of a MC within the lens. The polymerization of the MC, in turn, causes the change in optical properties.
(60) In some examples, the optical element of the invention has dispersed within it a MC. The MC is capable of diffusion within the lens; can be readily polymerized by exposure to a suitable external stimulus; and is compatible with the materials used to make the first polymer matrix of the lens.
(61) The method for providing an aspheric lens begins with the formation of the first polymer matrix. After the first polymer matrix is formed, the second polymer matrix is formed by exposing the first polymer matrix, which further comprises the MC, to an external stimulus. During this second polymerization, several changes occur within the optical element. The first change is the formation of a second polymer matrix comprising polymerized MC. The formation of the second polymer network can cause changes in the optical properties of the element, namely the refractive index. In addition, when the MC polymerizes, a difference in the chemical potential between the polymerized and unpolymerized region is induced. This in turn causes the unpolymerized MC to diffuse within the element, which reestablishes thermodynamic equilibrium of the optical element. If the optical element possesses sufficient elasticity, this migration of MC can cause swelling of the element in the area exposed to the stimulus. This, in turn, changes the shape of the element, causing changes in the optical properties. Whether the radius of curvature of the element and/or the refractive index of the element change depends upon (1) the nature of the optical element, (2) the MC incorporated into the element, (3) the duration that the element is exposed to the stimulus, and (4) the spatial intensity profile of the stimulus. A schematic depicting the process for increasing the power of the lens is displayed in
(62) The optical element is typically made of a first polymer matrix. Illustrative examples of a suitable first polymer matrix include: (1) polyacrylates such as polyalkyl acrylates and polyhydroxyalkyl acrylates; (2) polymethacrylates such as polymethyl methacrylate (PMMA), polyhydroxyethyl methacrylate (PHEMA), and polyhydroxypropyl methacrylate (HPMA); (3) polyvinyls such as polystyrene and polyvinylpyrrolidone (PNVP); (4) polysiloxanes such as polydimethylsiloxane; polyphosphazenes, and/or (5) copolymers thereof. U.S. Pat. No. 4,260,725 and patents and references cited therein (which are all incorporated herein by reference) provide more specific examples of suitable polymers that may be used to form the first polymer matrix.
(63) In preferred embodiments, where flexibility is desired, the first polymer matrix generally possesses a relatively low glass transition temperature (T.sub.g) such that the resulting IOL tends to exhibit fluid-like and/or elastomeric behavior, and is typically formed by cross-linking one or more polymeric starting materials wherein each polymeric starting material includes at least one cross-linkable group. In the case of an intraocular lens, the T.sub.g should be less than 25 C. This allows the lens to be folded, facilitating implantation.
(64) The crosslinking reaction of the polymeric starting material is accomplished via a hydrosilylation reaction. The general scheme for the hydrosilylation reaction is shown below.
(65) ##STR00009##
(66) During this crosslinking step, a high molecular weight long vinyl-capped silicone polymer and multi-functional vinyl-capped silicone resin are crosslinked using multifunctional hydrosilane crosslinkers. This crosslinking step forms the first polymer matrix in the presence of MC and photoinitiator.
(67) In some embodiments, the high molecular weight, long vinyl-capped silicone polymer has the following formula.
(68) ##STR00010##
(69) In some examples, in represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1, and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, in represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(70) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(71) In some embodiments, multi-functional vinyl-capped silicone resin has the following formula.
(72) ##STR00011##
(73) In some examples, x represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, x represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(74) In some examples, y represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, y represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(75) In some embodiments, multi-functional hydrosilane crosslinker has the following formula.
(76) ##STR00012##
(77) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(78) Illustrative examples of suitable cross-linkable groups include but are not limited to vinyl, hydride, acetoxy, alkoxy, amino, anhydride, aryloxy, carboxy, enoxy, epoxy, halide, isocyano, olefinic, and oxine. In more preferred embodiments, the polymeric starting material includes terminal monomers (also referred to as endcaps) that are either the same or different from the one or more monomers that comprise the polymeric starting material but include at least one cross-linkable group. In other words, the terminal monomers begin and end the polymeric starting material and include at least one cross-linkable group as part of its structure. Although it is not necessary for the practice of the present invention, the mechanism for cross-linking the polymeric starting material preferably is different than the mechanism for the stimulus-induced polymerization of the components that comprise the refraction modulating composition. For example, if the refraction modulating composition is polymerized by photoinduced polymerization, then it is preferred that the polymeric starting materials have cross-linkable groups that are polymerized by any mechanism other than photoinduced polymerization.
(79) An especially preferred class of polymeric starting materials for the formation of the first polymer matrix is polysiloxanes (also known as silicones) endcapped with a terminal monomer which includes a cross-linkable group selected from the group consisting of vinyl, acetoxy, amino, alkoxy, halide, hydroxy, and mercapto. Because silicone IOLs tend to be flexible and foldable, generally smaller incisions may be used during the IOL implantation procedure. An example of an especially preferred polymeric starting materials are vinyl endcapped dimethylsiloxane diphenylsiloxane copolymer, silicone resin, and silicone hydride crosslinker that are crosslinked via an addition polymerization by platinum catalyst to form the silicone matrix (see the above reaction scheme). Other such examples may be found in U.S. Pat. Nos. 5,236,970; 5,376,694; 5,278,258; 5,444,106; and, others similar to the described formulations. U.S. Pat. Nos. 5,236,970; 5,376,694; 5,278,258; and 5,444,106 are incorporated herein by reference in their entirety.
(80) The MC that is used in fabricating IOLs is as described above except that it has the additional requirement of biocompatibility. The MC is capable of stimulus-induced polymerization and may be a single component or multiple components so long as: (1) it is compatible with the formation of the first polymer matrix; (2) it remains capable of stimulus-induced polymerization after the formation of the first polymer matrix; and (3) it is freely diffusible within the first polymer matrix. In general, the same type of monomers that are used to form the first polymer matrix may be used as components of the refraction modulating composition. However, because of the requirement that the MC macromer must be diffusible within the first polymer matrix, the MC macromers generally tend to be smaller (i.e., have lower molecular weights) than the starting polymeric materials used to form the first polymer matrix. In addition to the one or more monomers, the MC may include other components such as initiators and sensitizers that facilitate the formation of the second polymer network.
(81) In preferred embodiments, the stimulus-induced polymerization is photopolymerization. In other words, the one or more monomers or macromers that comprise the refraction modulating composition each preferably includes at least one group that is capable of photopolymerization. Illustrative examples of such photopolymerizable groups include but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. In more preferred embodiments, the refraction modulating composition includes a photoinitiator (any compound used to generate free radicals) either alone or in the presence of a sensitizer. Examples of suitable photoinitiators include acetophenones (e.g., substituted haloacetophenones, and diethoxyacetophenone); 2,4-dichloromethyl-1,3,5-trazines; benzoin methyl ether; and o-benzoyl oximino ketone. Examples of suitable sensitizers include p-(dialkyiamino)aryl aldehyde; N-alkylindolylidene; and bis[p-(dialkylamino)benzylidene]ketone.
(82) Because of the preference for flexible and foldable IOLs, an especially preferred class of MC monomers is polysiloxanes endcapped with a terminal siloxane moiety that includes a photopolymerizable group. Non-limiting examples of a suitable photopolymerizable group include, but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. An illustrative representation of such a monomer is:
XYX.sup.1
wherein Y is a siloxane which may be a monomer, a homopolymer or a copolymer formed from any number of siloxane units, and X and X.sup.1 may be the same or different and are each independently a terminal siloxane moiety that includes a photopolymerizable group. Non-limiting examples of a suitable photopolymerizable group include, but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. An illustrative example of Y includes:
(83) ##STR00013##
wherein m and n are independently each an integer; and, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently each hydrogen, alkyl (substituted, primary, secondary, tertiary, cycloalkyl), aryl, or heteroaryl. In preferred embodiments, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently C.sub.1-C.sub.10 alkyl or phenyl. Because MC monomers with a relatively high aryl content have been found to produce larger changes in the refractive index of the inventive lens, it is generally preferred that at least one of R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is an aryl, particularly phenyl. In more preferred embodiments, R.sup.1, R.sup.2, and R.sup.3 are the same and are methyl, ethyl or propyl with the proviso that R.sup.4 is phenyl.
(84) In some examples, m represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, m represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(85) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(86) Illustrative examples of X and X.sup.1 (or X.sup.1 and X depending on how the MC polymer is depicted) are:
(87) ##STR00014##
(88) respectively wherein: R.sup.5 and R.sup.6 are independently each hydrogen, alkyl, aryl, or heteroaryl; and Z is a photopolymerizable group.
(89) In preferred embodiments R.sup.5 and R.sup.6 are independently each C.sub.1-C.sub.10 alkyl or phenyl and Z is a photopolymerizable group that includes a moiety selected from the group consisting of acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. In more preferred embodiments, R.sup.5 and R.sup.6 are methyl, ethyl, or propyl and Z is a photopolymerizable group that includes an acrylate or methacrylate moiety.
(90) In some embodiments, a MC macromer has the following formula:
(91) ##STR00015##
(92) wherein X and X.sup.1 are the same as defined above, and wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are the same as defined above. In some examples, m represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, m represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(93) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(94) In general, a suitable modifying composition consists of a lower molecular weight polydimethyl-siloxane macromer containing polymerizable methacrylate functional end groups and a bezoin photoinitiator. In some embodiments, a suitable modifying composition has the following formula.
(95) ##STR00016##
(96) The above structure is a polydimethyl siloxane end-capped with photopolymerizable methacrylate functional groups. In some examples, x represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, x represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(97) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(98) In some embodiments, a suitable modifying composition has the following formula.
(99) ##STR00017##
(100) The above modifying composition has a structure comprising a polydimethyl siloxane end-capped with benzoin photoinitiator. In some examples, x represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, x represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(101) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(102) Additional illustrative examples of such MC monomers include dimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyl dimethylsilane group (see below);
(103) ##STR00018##
(104) In some examples, m represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, m represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(105) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(106) Another illustrative examples of such MC monomers includes dimethylsiloxane-methylphenylsiloxane copolymer endcapped with a methacryloxypropyl dimethylsilane group (see below);
(107) ##STR00019##
(108) In some examples, m represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, m represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(109) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(110) A preferred modifying composition is the dimethylsiloxane macromer endcapped with a methacryloxypropyldimethylsilane group (see below).
(111) ##STR00020##
(112) In some examples, x represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, x represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(113) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(114) Although any suitable method may be used, a ring-opening reaction of one or more cyclic siloxanes in the presence of triflic acid has been found to be a particularly efficient method of making a class of MC monomers. Briefly, the method comprises contacting a cyclic siloxane with a compound of the formula:
(115) ##STR00021##
in the presence of triflic acid wherein R.sup.5 and R.sup.6 are independently each hydrogen, alkyl, aryl, or heteroaryl; and Z is a photopolymerizable group. The cyclic siloxane may be a cyclic siloxane monomer, homopolymer, or copolymer. Alternatively, more than one cyclic siloxane may be used. For example, a cyclic dimethylsiloxane tetrameter and a cyclic methyl-phenylsiloxane trimer are contacted with bis-methacryloxypropyltetramethyldisiloxane in the presence of triflic acid to form a dimethyl-siloxane methyl-phenylsiloxane copolymer that is endcapped with a methacryloxylpropyl-dimethylsilane group, an especially preferred MC monomer, such as the MC monomer shown below.
(116) ##STR00022##
(117) In some examples, x represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, x represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(118) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(119) In addition to the silicone-based MCs described above, acrylate-based MC can also be used in the practice of the invention. The acrylate-based macromers of the invention have the general structure wherein X and X.sup.1 may be the same or different and/or are each independently a terminal siloxane moiety that includes a photopolymerizable group. Non-limiting examples of a suitable photopolymerizable group include, but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl
X-A.sub.n-Q-A.sub.n-X.sup.1
or
X-A.sub.n-A.sup.1.sub.m-Q-A.sup.1.sub.m-A.sub.n-X.sup.1
wherein Q is an acrylate moiety capable of acting as an initiator for Atom Transfer Radical Polymerization (ATRP), A and A.sup.1 have the general structure:
(120) ##STR00023##
(121) wherein R.sup.1 is selected from the group comprising alkyls, halogenated alkyls, aryls and halogenated aryls and X and X.sup.1 are groups containing photopolymerizable moieties and m and n are integers. In some examples, m represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, m represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(122) In some examples, n represents an integer having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges. In some examples, n represents an integer having an average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of the aforementioned ranges.
(123) In one embodiment the acrylate based MC macromer has the formula:
(124) ##STR00024##
(125) wherein R.sup.2 is alkyl or halogenated alkyl; R.sup.3 is alkyl, halogenated alkyl, aryl or halogenated aryls; R.sup.4 is alkyl, halogenated alkyl, aryl or halogenated aryl; and, with the proviso that R.sup.3 and R.sup.4 are different. In some embodiments, the value of n is between 1 and 200; 1 and 190; 1 and 180; 1 and 170; 1 and 160; 1 and 150; 1 and 140; 1 and 130; 1 and 120; 1 and 110; 1 and 100; 1 and 90; 1 and 80; 1 and 70; 1 and 60; 1 and 50; 1 and 40; 1 and 30; 1 and 20; 1 and 10; or any range in between. For example, when the value of n is between 1 and 200, this also contemplates a value of n between 17 and 24. In some embodiments the value of m is between 1 and 200; 1 and 190; 1 and 180; 1 and 170; 1 and 160; 1 and 150; 1 and 140; 1 and 130; 1 and 120; 1 and 110; 1 and 100; 1 and 90; 1 and 80; 1 and 70; 1 and 60; 1 and 50; 1 and 40; 1 and 30; 1 and 20; 1 and 10; or any range in between. For example, when the value of m is between 1 and 200, this also contemplates a value of m between 17 and 24.
(126) After the optical element is formed, it is then positioned in the area where the optical properties are to be modified. For an intraocular lens, this means implantation into the eye using known procedures. Once the element is in place and is allowed to adjust to its environment, it is then possible to modify the optical properties of the element through exposure to an external stimulus.
(127) The nature of the external stimulus can vary but it must be capable of reducing polymerization of the MC without adversely affecting the properties of the optical element. Typical external stimuli that can be used in practice of the invention include heat and light, with light preferred. In the case of intraocular lenses, ultraviolet or infrared radiation is preferred with ultraviolet light most preferred.
(128) When the element is exposed to the external stimulus, the MC polymerization forms a second polymer matrix, interspersed within the first polymer matrix. When the polymerization is localized or when only a portion of the MC is polymerized, there is a difference in the chemical potential between the reacted and unreacted regions of the lens. The MC then migrates within the element to reestablish the thermodynamic equilibrium within the optical element.
(129) The formation of the second polymer matrix and the re-distribution of the MC can each affect the optical properties of the element. For example, the formation of the second polymer matrix can cause changes in the refractive index of the element. The migration of the modifying compound can alter the overall shape of the element, further affecting the optical properties by changing the radii of curvatures of the optical element.
(130) It is possible to expose the optical element to a spatially defined irradiance profile to create a lens with different optical properties. In one embodiment, it is possible to create an intraocular lens that can be converted into an aspheric lens after implantation. This is accomplished by exposing the lens to a mathematically defined spatial irradiance profile. An example of the type of profiles that can be used to induce asphericity in the lens are of the form
Asph()A.sup.4B.sup.2+1(Equation 1)
(131) Where A and B are coefficients and is a radial coordinate. A normalized plot of this function, where A=B=4, is displayed in
(132) Another approach is to linearly combine weighted amounts of the profile (Asph) displayed in equation 1 with spatial irradiance profiles that are currently used to correct for spherical refractive errors and spherocylindrical refractive errors as well as with Power Neutral Profiles, i.e., profiles that neither add or subtract refractive power from the LAL. This approach has the dual benefits of correcting the lower aberrations, e.g. sphere and cylinder, along with imparting the requisite amount of induced asphericity to provide increased depth of focus. This can be described mathematically as follows:
Profile()=SCN()+Asph()(Equation 2)
(133) where SCN() refers to either a spherical, spherocylindrical or power neutral spatial irradiance profile, Asph() is the same as in equation 1, and is a weighting factor that can range from 0 to 1. As an example of this approach, consider the cross-sectional profiles shown in
(134) By way of a reaction sequence, the following example shows how the formation of the second polymer matrix and the re-distribution of the MC is accomplished. In the example provided below, the MC having the formula:
(135) ##STR00025##
(136) is exposed to UV light, thereby creating a radical species. This process is represented schematically in the reaction scheme below.
(137) ##STR00026##
(138) After exposing the MC to UV light, the resulting radical species are free to react with the first polymer matrix. In the example, below the first polymer matrix was formed using a polymer having the following structure:
(139) ##STR00027##
(140) The radical species generated by exposing the MC to UV light then reacts with the first polymer matrix according to the reaction scheme below:
(141) ##STR00028##
(142) The reaction scheme for photopolymerization of photo-reactive MC in the presence of the first polymer lens matrix is the same for the adjustment and lock-in procedures. The difference between the adjustment procedure and lock-in procedure is the spatial irradiance profiles applied to each procedure.
EXAMPLES
(143) The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
Example 1
(144) A series of light adjustable lenses containing a silicone-based MC were prepared using standard molding techniques known to those skilled in the art. The lens had a first polymer matrix prepared from a silicone hydride crosslinked vinyl endcapped diphenylsiloxane dimethylsiloxane. The first polymer matrix comprised about 70 weight % of the lens. The lens also comprised about 30 weight % of a MC (methacrylate endcapped polydimethylsiloxane), 1 weight % (based on MC) of a photoinitiator (benzoin-tetrasiloxane-benzoin), and 0.04 weight % (based on MC) UV absorber. The lenses had an initial nominal power of +20.0 diopters. Twelve groups, of four LALs each, were exposed to a spatial irradiance profile defined by Equation 2 with beta values ranging from 0.05 to 0.57. Table 1 summarizes the specific spatial irradiance profile, average irradiance, and time applied to each of the LAL groups. At 48 hours post irradiation, the wavefronts of each of the lenses was measured. The measured 4.sup.th (Z12) and 6.sup.th (Z24) order spherical aberration values for each of the 12 irradiation groups were averaged together and plotted as a function of increasing value as show in
(145) TABLE-US-00001 TABLE 1 Summary of treatment conditions and induced spherical aberration for those lenses that did not receive a prior adjustment. The measurement aperture was 4 mm for all spherical aberration measurements. Duration Applied Power Bm Size 4th Order SA 6th Order SA Lens ID Profile (sec) (mW) (mm) Z12 (m) Z24 (m) 6699 In-vitro PN Profile + Beta = 0.05 90 4.130 5.30 0.194 0.016 6701 In-vitro PN Profile + Beta = 0.05 90 4.130 5.30 0.115 0.050 6706 In-vitro PN Profile + Beta = 0.05 90 4.130 5.30 0.003 0.054 6708 In-vitro PN Profile + Beta = 0.05 90 4.130 5.30 0.029 0.053 Average 0.085 0.043 St. Dev 0.087 0.018 189-26 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30 0.019 0.017 189-29 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30 0.024 0.017 189-31 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30 0.020 0.016 189-33 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30 0.036 0.013 Average 0.025 0.016 St. Dev 0.008 0.002 189-27 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 0.056 0.013 189-30 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 0.055 0.013 189-32 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 0.054 0.012 189-34 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 0.060 0.010 Average 0.056 0.012 St. Dev 0.003 0.001 189-35 In-vitro PN Profile + Beta = 0.20 90 3.510 5.30 0.088 0.018 189-38 In-vitro PN Profile + Beta = 0.20 90 3.510 5.30 0.088 0.013 189-40 In-vitro PN Profile + Beta = 0.20 90 3.510 5.30 0.083 0.018 189-44 In-vitro PN Profile + Beta = 0.20 90 3.510 5.30 0.081 0.013 Average 0.085 0.015 St. Dev 0.003 0.003 189-37 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30 0.107 0.013 189-39 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30 0.111 0.006 189-41 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30 0.106 0.009 189-45 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30 0.130 0.006 Average 0.113 0.009 St. Dev 0.011 0.003 185-3-2 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 0.151 0.010 185-3-15 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 0.156 0.008 188-2-18 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 0.163 0.012 189-47 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 0.148 0.007 Average 0.155 0.009 St. Dev 0.007 0.002 185-3-11 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 0.193 0.005 188-2-16 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 0.194 0.003 189-46 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 0.192 0.002 189-48 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 0.182 0.002 Average 0.190 0.003 St. Dev 0.006 0.002 6700 In-vitro PN Profile + Beta = 0.40 90 2.900 5.30 0.240 0.013 6704 In-vitro PN Profile + Beta = 0.40 90 2.900 5.30 0.241 0.011 6707 In-vitro PN Profile + Beta = 0.40 90 2.900 5.30 0.222 0.011 6709 In-vitro PN Profile + Beta = 0.40 90 2.900 5.30 0.224 0.017 Average 0.232 0.013 St. Dev 0.010 0.003 6710 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 0.277 0.004 6712 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 0.284 0.003 6715 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 0.274 0.006 6717 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 0.266 0.002 Average 0.275 0.003 St. Dev 0.007 0.003 6713 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 0.303 0.001 6716 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 0.322 0.002 6718 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 0.318 0.009 Average 0.314 0.003 St. Dev 0.010 0.005 6719 In-vitro PN Profile + Beta = 0.55 90 2.440 5.30 0.356 0.009 6723 In-vitro PN Profile + Beta = 0.55 90 2.440 5.30 0.347 0.016 6727 In-vitro PN Profile + Beta = 0.55 90 2.440 5.30 0.350 0.011 6729 In-vitro PN Profile + Beta = 0.55 90 2.440 5.30 0.350 0.021 Average 0.351 0.014 St. Dev 0.004 0.006 6721 In-vitro PN Profile + Beta = 0.57 90 2.380 5.30 0.368 0.015 6725 In-vitro PN Profile + Beta = 0.57 90 2.380 5.30 0.350 0.026 6728 In-vitro PN Profile + Beta = 0.57 90 2.380 5.30 0.359 0.019 6730 In-vitro PN Profile + Beta = 0.57 90 2.380 5.30 0.385 0.030 Average 0.366 0.022 St. Dev 0.015 0.007
(146) Inspection of the plot indicates several interesting features. The first is the nearly linearly increase in induced 4.sup.th order spherical aberration as a function of increasing value. The second feature is the nearly complete absence of any 6.sup.th order spherical aberration induction, indicating that the induced spherical aberration is essentially pure 4.sup.th order spherical aberration. This is important because it has been shown that the presence of 6.sup.th order spherical aberration will have the affect of nulling out any induced depth of focus produced by the induction of negative 4.sup.th order spherical aberration. (Thibos et al., 2004) The third feature to note is the small standard deviation in the average, induced 4.sup.th order spherical aberration for a specific value. This fact indicates that it is possible to adjust the amount of asphericity in the LAL by targeted, discrete values, which will allow true customization of patients' depth of focus. And finally, as written above, the targeted amount of total ocular 4.sup.th order spherical aberration for optimizing visual acuity between 40 cm and distance emmetropia is 0.125 m. Inspection of the data in Table 2 and
(147) The above example involved irradiating LALs that had not received a prior adjustment. However, there will be instances where it is necessary to first adjust the spherical and/or spherocylindrical power of the LAL before the aspheric adjustment. The LAL is a closed thermodynamic system, i.e. we can't add or remove particles, MC, from the lens. As a consequence, each subsequent refractive adjustment consumes MC leaving less for subsequent adjustments. In addition, upon polymerization of MC during adjustment, the polymerized MC forms an interpenetrating matrix with the host matrix polymer. This action has the effect of increasing the stiffness of the lens. Because the refractive change, i.e. spherical, spherocylindrical, aspheric, etc., of the LAL is accomplished by a shape change, the amount of induced asphericity after an initial adjustment should be reduced for same treatment conditions as with the no prior adjustment cases summarized in
(148) To investigate this, a series of LALs were initially given either a myopic or hyperopic primary adjustment followed by an aspheric treatment 48 hours post the initial, primary adjustment.
(149) Inspection and comparison of the data for the different treatment conditions indicate several interesting trends. The first overall theme is that, as expected, increasing the beta value, which effectively increases the amount of aspheric character of the treatment beam, has the effect of increasing the amount of induced 4.sup.th order asphericity in the LAL. This is true whether the LAL initially received a primary adjustment or if the LAL has received no prior adjustment. The second thing to note is that for a given beta, mediated aspheric profile, the type of refractive adjustment preceding the aspheric treatment directly impacts how much 4.sup.th order asphericity is induced in the lens. For example, consider the three different sets of LALs that were adjusted with the =0.57 aspheric profile after a hyperopic adjustment, a myopic adjustment, and no adjustment. Inspection of the graph indicates that those lenses receiving no prior adjustment displayed the largest amount of induced 4.sup.th order spherical aberration, followed by the LALs that initially received a myopic adjustment, with the LALs after a hyperopic adjustment showing the smallest amount of induced asphericity. The reasons for this general trend are twofold. The first, which was discussed above, is due to the simple fact that the LALs that received no prior adjustment obviously have more starting MC and the LAL matrix is not as stiff as compared to the other two sets of LALs and thus, for the same given aspheric dose, should show more 4.sup.th order asphericity induction. The reasons why the LALs receiving an initial myopic adjustment display greater amounts of induced 4th order spherical aberration as compared to those LALs receiving a hyperopic adjustment as their primary adjustment, even though the magnitude of the refractive change (1.0 D vs +1.0 D) is the same, can be explained by the fact that the total energy underneath the spatial irradiance profile for the given myopic adjustment is less than that as compared to the hyperopic adjustment profile. Because of this fact, more macromer will be consumed during the initial hyperopic adjustment and a stronger, interpenetrating network will be formed, thus preventing more aspheric induction. Another important aspect of the data to note, is that regardless of prior adjustment, the application of the aspheric treatment does not induce any 6.sup.th order spherical aberration.
Example 2
(150) To test the ability of the aspheric adjustment profiles to induce enough asphericity to provide patients' with increased depth of focus, a series of subjects were implanted with the light adjustable lens after routine cataract surgery, given a prior treatment to correct for postoperative residual sphere and cylinder, and then given an aspheric adjustment using the corneal compensated versions of the profiles described in Example 1.
(151) Inspection of the graph in
(152) TABLE-US-00002 TABLE 1 Monocular visual acuity (VA) results for those eyes receiving an aspheric treatment (n = 32). VA FAR 60 cm 40 cm Far BCVA 20/20 9/32 (28%) 17/32 (53%) 2/32 (6%) 21/32 (65%) 20/25 23/32 (72%) 27/32 (84%) 11/32 (35%) 31/32 (97%) 20/32 28/32 (88%) 32/32 (100%) 24/32 (75%) 32/32 (100%) 20/40 32/32 (100%) 32/32 (100%) 31/32 (97%) 32/32 (100%) 20/60 32/32 (100%) 32/32 (100%) 32/32 (100%) 32/32 (100%)
(153) TABLE-US-00003 TABLE 2 Monocular visual acuity (VA) results for those LAL eyes adjusted for distance visual acuity only (n = 12). VA FAR 60 cm 40 cm Far BCVA 20/20 10/12 (83%) 1/12 (8%) 0/12 (0%) 12/12 (100%) 20/25 12/12 (100%) 3/12 (25%) 0/12 (0%) 12/12 (100%) 20/32 12/12 (100%) 8/12 (67%) 1/12 (8%) 12/12 (100%) 20/40 12/12 (100%) 12/12 (100%) 7/12 (58%) 12/12 (100%) 20/60 12/12 (100%) 12/12 (100%) 12/12 (100%) 12/12 (100%)
(154) As indicated in
(155) TABLE-US-00004 TABLE 3 Monocular visual acuity (VA) results for those eyes with low amounts of final 4.sup.th order spherical aberration, 0.04 to 0.10 m (n = 23). VA FAR 60 cm 40 cm Far BCVA 20/20 7/23 (30%) 12/23 (8%) 0/23 (0%) 15/23 (65%) (J1+) 20/25 15/23 (74%) 19/23 (83%) 5/23 (22%) 22/23 (96%) (J1) 20/32 20/23 (100%) 23/23 (100%) 15/23 (65%) 12/12 (100%) (J2) 20/40 23/23 (100%) 23/23 (100%) 23/23 (100%) 12/12 (100%) (J3) 20/60 23/23 (100%) 23/23 (100%) 23/23 (100%) 12/12 (100%)
(156) TABLE-US-00005 TABLE 4 Monocular visual acuity (VA) results for those eyes with high amounts of final 4.sup.th order spherical aberration, 0.11 to 0.23 m (n = 9). VA FAR 60 cm 40 cm Far BCVA 20/20 (J1+) 2/9 (22%) 4/9 (8%) 2/9 (22%) 6/9 (67%) 20/25 (J1) 5/9 (56%) 7/9 (78%) 7/9 (78%) 8/9 (89%) 20/32 (J2) 8/9 (89%) 8/9 (89%) 9/9 (100%) 9/9 (100%) 20/40 (J3) 9/9 (100%) 9/9 (100%) 9/9 (100%) 9/9 (100%) 20/60 9/9 (100%) 9/9 (100%) 9/9 (100%) 9/9 (100%)
(157) The above discussion considered the monocular visual acuities of the treated eyes, only. However, one approach that will optimize post LAL implantation patients' vision at all distances is to correct one of the patients' eyes (usually the dominant eye) to distance emmetropia and then to adjust the other eye of the patient first to distance emmetropia followed by application of the aspheric treatment. As an example of this procedure, consider the data displayed in
(158) TABLE-US-00006 TABLE 5 Binocular visual acuity (VA) results for those eyes with low amounts of final 4.sup.th order spherical aberration, 0.04 to 0.10 mm in their non-dominant eye and with their other eye adjusted for distance emmetropia. The refraction in the dominant eye ranged from +0.25 D to 0.25 D (n=10). VA FAR 60 cm 40 cm 30 cm 20/20 (J1+) 6/10 (60%) 8/10(80%) 1/10 (10%) 0/10 (0%) 20/25 (J1) 10/10 (100%) 10/10(100%) 4/10 (40%) 0/10 (0%) 20/32 (J2) 10/10 (100%) 10/10(100%) 10/10 (100%) 3/10 (30%) 20/40 (J3) 10/10 (100%) 10/10(100%) 10/10 (100%) 8/10 (80%) 20/60 10/10 (100%) 10/10(100%) 10/10 (100%) 10/10 (100%)
(159) Combining this binocular approach with those eyes having high amounts of induced asphericity (0.11 m to 0.23 m), indicates that 100% (4/4) of the patients possessed an uncorrected visual of 20/25 or better from 40 cm to distance emmetropia.
(160) TABLE-US-00007 TABLE 6 Binocular visual acuity (VA) results for those eyes with high amounts of final 4.sup.th order spherical aberration, 0.11 to 0.23 m in their non-dominant eye and with their other eye adjusted for distance emmetropia. The refraction in the dominant eye ranged from +0.25 D to 0.25 D (n = 4). VA FAR 60 cm 40 cm 30 cm 20/20 (J1+) 4/4 (100%) 3/4 (75%) 1/10 (10%) 0/4 (0%) 20/25 (J1) 4/4 (100%) 4/4 (100%) 4/4 (100%) 1/4 (25%) 20/32 (J2) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4 (100%) 20/40 (J3) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4 (100%) 20/60 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4 (100%)
Example 3
(161) General examples disclosed herein include an optical element composed of matrix polymer and a modulating composition (MC) that can be polymerized by an external stimulus (e.g. heat, light, etc) to control the amount of induced asphericity.
(162) In each of the aforementioned examples, the lens may include an optical element that is a lens. In additional examples, the optical element is an intraocular lens (IOL). Also, the amount of induced asphericity is controlled by the application of a specific spatial irradiance profile. In some examples, the amount of induced asphericity is induced monocularly to induce extended depth of focus.
(163) In particular examples, the amount of induced asphericity is tailored to provide intermediate vision (60-80 cm) or near vision (30-40 cm). In specific embodiments, the amount of induced asphericity can be customized for specific individual values.
(164) In certain embodiments, the amount of induced asphericity is induced binocularly to induce extended depth of focus. In particular examples, one eye is tailored for intermediate (60-80 cm) vision by the induction of a particular value of asphericity and the other eye is corrected for distance emmetropia. In alternate embodiments, one eye is tailored for near vision (30-40 cm) by the induction of a particular value of asphericity and the other eye is corrected for distance emmetropia. In further embodiments, both eyes are tailored for intermediate (60-80 cm) vision by the induction of particular value of asphericity. In yet another embodiment, both eyes are tailored for near (30-40 cm) vision by the induction of particular value of asphericity. In some embodiments, one eye is tailored for intermediate (60-80 cm) vision by the induction of negative asphericity and the other eye is tailored for intermediate vision (60-80 cm) vision by the induction of positive asphericity. In particular embodiments, one eye is tailored for near vision (30-40 cm) vision by the induction of negative asphericity and the other eye is tailored for near vision (30-40 cm) vision by the induction of positive asphericity.
(165) In some examples, the amount of induced asphericity of the lens is tailored to compensate for the spherical aberration of the cornea. In other examples, the amount of induced asphericity of both lenses are tailored to compensate for the spherical aberration of their respective corneas. In alternate examples, one lens is adjusted to remove the spherical aberration of the entire eye and the other lens is adjusted to induce asphercity for intermediate vision (60-80 cm). In some examples, one lens is adjusted to remove the spherical aberration of the entire eye and the other lens is adjusted to induce asphercity for near vision (30-40 cm).
REFERENCES
(166) All patents and publications mentioned in the specification are indicative of the level of those skilled in the art to which the invention pertains. All patents and publications are herein incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.
PATENTS
(167) U.S. Pat. No. 4,260,725 U.S. Pat. No. 5,225,858 U.S. Pat. No. 5,236,970 U.S. Pat. No. 5,278,258 U.S. Pat. No. 5,376,694 U.S. Pat. No. 5,444,106
PUBLICATIONS
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(169) Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present invention, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present invention. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.