U.S. patent application number 10/192017 was filed with the patent office on 2003-03-13 for intraoccular lenses capable of in vivo power adjustment and method for same.
Invention is credited to Grubbs, Robert H., Jethmalani, Jagdish M., Kornfield, Julia A., Maloney, Robert K., Sandstedt, Christian A., Schwartz, Daniel M..
Application Number | 20030048411 10/192017 |
Document ID | / |
Family ID | 27494026 |
Filed Date | 2003-03-13 |
United States Patent
Application |
20030048411 |
Kind Code |
A1 |
Jethmalani, Jagdish M. ; et
al. |
March 13, 2003 |
Intraoccular lenses capable of in vivo power adjustment and method
for same
Abstract
A method for evaluating the effectiveness of adjustable optical
implants is provided The implants are first inserted into a test
subject. The implant is then exposed to an external stimulus, such
as light, to induce a change in the properties of the implant. The
implants are then evaluated to determine the nature and extent of
the change in properties.
Inventors: |
Jethmalani, Jagdish M.;
(Pasadena, CA) ; Maloney, Robert K.; (Pacific
Palisades, CA) ; Grubbs, Robert H.; (South Pasadena,
CA) ; Kornfield, Julia A.; (Pasadena, CA) ;
Sandstedt, Christian A.; (Pasadena, CA) ; Schwartz,
Daniel M.; (San Francisco, CA) |
Correspondence
Address: |
CHRISTIE, PARKER & HALE, LLP
P.O. BOX 7068
PASADENA
CA
91109-7068
US
|
Family ID: |
27494026 |
Appl. No.: |
10/192017 |
Filed: |
July 10, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10192017 |
Jul 10, 2002 |
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09416044 |
Oct 8, 1999 |
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6450642 |
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60115617 |
Jan 12, 1999 |
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60132871 |
May 5, 1999 |
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60140298 |
Jun 17, 1999 |
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Current U.S.
Class: |
351/205 |
Current CPC
Class: |
G02B 1/043 20130101;
A61L 2430/16 20130101; G02C 7/04 20130101; C08L 83/04 20130101;
C08L 83/04 20130101; A61L 27/18 20130101; G02B 3/00 20130101; G02C
2202/14 20130101; A61F 2/1635 20130101; G02B 1/043 20130101; A61L
27/18 20130101; A61F 2/1627 20130101 |
Class at
Publication: |
351/205 |
International
Class: |
A61B 003/10 |
Claims
What is claimed is:
1. A method for testing biocompatibility of an optical element
containing a refraction modulating composition, comprising the
steps of: a) forming an optical element of a polymer with macromers
dispersed therein, wherein the macromers is capable of
stimulus-induced polymerization, such that a stimulus causes a
desired change of refraction; b) sterilizing the optical element;
c) implanting the optical element in an eye; d) extracting the
optical element from the eye after a period of time and testing for
toxicity.
2. The method of claim 1, and further including the step of: a)
forming the optical element with a refraction modulating
composition selected from the group consisting of an acrylate,
methacrylate, vinyl, siloxane and phosphazene.
3. The method of claim 1, and further including the step of: a)
forming the optical element of polysiloxane matrix and a refraction
modulating composition dispersed therein.
4. The method of claim 1, and further including the step of: a)
exposing at least a portion of the optical element to a stimulus
after the step of implanting the optical element, whereby the
stimulus induces the polymerization of the refraction modulating
composition, such that the stimulus causes a desired change of
refraction.
5. The method of claim 4, and further including the step of: a)
waiting an interval of time after the step of exposing, and b)
re-exposing the portion of the optical element to the stimulus to
induce the further polymerization of the refraction modulation
composition which the portion, such that the stimulus produces a
desired change of refraction.
6. The method of claim 4, and further including the step of: a) the
step of exposing includes exposing at least a portion of the
optical element to stimulus from a light source.
7. The method of claim 4, and further including the steps of: a)
implanting a plurality of optical elements in a like number of
rabbit eyes; b) exposing at least a portion of a number of the
optical elements to a stimulus after the step of implanting the
optical elements, whereby the stimulus induces the polymerization
of the refraction modulating composition, such that the stimulus
causes a desired change of refraction; and c) explanting the
optical elements from the rabbit eyes and testing for toxicity.
8. The method of claim 7, and further including the steps of: a)
maintaining at least some of the optical elements in the rabbit
eyes without exposing the optical elements to a stimulus; and b)
explanting the optical elements from the rabbit eyes and testing
for toxicity.
9. A method of evaluating an adjustable optical implant comprising:
a) Inserting an adjustable optical implant into a test subject. b)
Adjusting the optical properties of said implant in vivo; and c)
Evaluating the change in optical properties of the implant.
10. The method of claim 9 wherein the implant comprises macromers
capable of inducing changes in the optical properties of the
implant when the macromers are exposed to an external stimulus.
11. The method of claim 9 wherein the adjusting of the optical
properties of the implant is accomplished by exposing at least a
portion of said implant to an external stimulus.
12. The method of claim 10 wherein the external stimulus is
light.
13. The method of claim 10 wherein the external stimulus is
ultraviolet light.
14. The method of claim 10 wherein the implant is an intraoccular
lens.
15. A method for evaluating an adjustable optical implant
comprising a) Inserting an adjustable optical implant in a test
subject; b) Adjusting the optical properties of the implant in
vivo; and c) Evaluating the changes in optical properties and the
biocompatability of the implant.
16. The method of claim 15 wherein said optical implant comprises
macromers which can induce changes in the optical properties of the
implant upon exposure to an external stimulus.
17. The method of claim 15 wherein said adjusting step is
accomplished by exposing at least a portion of said implant to an
external stimulus.
18. The method of claim 17 wherein said external stimulus is
light.
19. The method of claim 18 wherein said light is ultraviolet
light.
20. The method of claim 15 further comprising the step of
evaluating the biocompatibility of the implant.
21. The method of claim 15 wherein the implant is an intraoccular
lens.
22. A method of evaluating an adjustable optical implant
comprising: a) Inserting an adjustable optical implant into a test
subject. b) Adjusting the optical properties of said implant in
vivo; and c) Evaluating the change in optical properties in the
implant in vivo.
23. The method of claim 22 wherein the adjusting of the optical
properties of the implant is accomplished by exposing at least a
portion of said implant to an external stimulus.
24. The method of claim 23 wherein the external stimulus is
light.
25. The method of claim 23 wherein the external stimulus is
ultraviolet light.
26. The method of claim 22 wherein the implant is an intraoccular
lens.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation-in-part of U.S. application Ser. No.
09/416,044 filed Oct. 8, 1999; which claims priority of U.S.
Provisional Application No. 60/115,617 filed Jan. 12, 1999; claims
priority of U.S. Provisional Application No. 60/132,871 filed May
5, 1999; and claims priority of U.S. Provisional Application No.
60/140,298 filed Jun. 17, 1999; and which is fully incorporated
herein by reference.
TECHNICAL FIELD
[0002] The present invention is directed to a system and method
which relates to a novel method for evaluating optical implants
such as intraoccular lenses (IOLs). In the present invention, the
implants are placed in a non-human test subject and evaluated for
biocompatibility and operability. The method is useful in the
design of novel implants as well as obtaining data concerning the
safety and operability of the lenses. The method is particularly
applicable to novel IOLs whose optical properties can be
manipulated after the lens has been implanted.
BACKGROUND OF THE INVENTION
[0003] Optical implants have long been used to correct vision
problems or to affect changes in "subjects" vision. The most widely
used optical implant in the intraoccular lens (IOL) which is used
to replace a patient's natural lens when the lens can no longer
function. IOLs are most often used when a patient develops
cataracts such that normal vision is impossible.
[0004] Until recently, the optical properties of optical implant
such as IOLs were predetermined prior to implantation. In the case
of IOLs, the ophthalmologist would estimate such properties as the
lens power and shape based on pre-operation examination of the
patient's eye. A lens meeting those requirements would then be
implanted into the eye after the natural lens was removed. While
these procedures are generally successful in restoring sight to a
patient, until recently, there was no noninvasive procedure for
adjusting the optical properties of the lens. Thus, if the
surgeon's estimates were incorrect, the patient might still be
required to use spectacles or the like to achieve optimum
vision.
[0005] Recently, a novel type of optical implant has been developed
which allows for manipulation of the optical properties of the
implant after it has been implanted in the patient. PCT/US99/23728
discloses a novel implant whose optical properties can be adjusted
post fabrication by one or more regions of the implant to an
external stimulus such as light. These novel implants allow a
surgeon to adjust the optical properties of an IOL after it has
been implanted.
BRIEF SUMMARY OF THE INVENTION
[0006] The invention is a method that allows for testing of both
the safety and operability of optical implants. In one embodiment,
it is a method for evaluating the safety and operability of novel
IOLs whose optical properties can be manipulated in vivo.
[0007] In practice of the invention, an optical implant is
implanted in a non-human test subject. After allowing for wound
healing, the implant is then evaluated for biocompatibility and
operability. By operability, we mean adjustment of lens dose. In
the case of implants which are capable of post implant manipulation
of optical properties, this includes manipulating the optical
properties in the prescribed manner and then evaluating the implant
to set if the desired changes occur and are maintained for the
desired time period.
[0008] In a preferred embodiment, the method involves implanting an
adjustable IOL in a non-human test subject. By the term "Adjustable
IOL" we refer to IOLs whose optical properties can be manipulated
or adjusted post implantation without resort to invasive
procedures. Generally, this is accomplished by preparing an implant
which has macromers distributed therein. These macromers respond to
external stimuli such as light, causing changes in the optical
properties of the implant. A more detailed description of these
types of implants can be found in PCT/US 99/23728.
[0009] After the implant has been placed in the test subject, and
following wound healing, the optical properties of the lens are
manipulated in the prescribed manner. In the preferred method, this
is accomplished by exposing the lens to an external stimulus, such
as light. Ultraviolet light is most preferred.
[0010] After the optical properties have been manipulated in the
desired manner, the implants are then evaluated for safety,
including biocompatibility, and operability, e.g. whether the
desired changes in optical properties have taken place. These tests
are done using standard methods such as examining the test
subject's eyes for evidence of inflammation and physical
examination of the lens implant for changes in optical properties.
These evaluations can occur either in vivo or ex vivo.
[0011] The foregoing has outlined rather broadly the features and
technical advantages of the present invention in order that the
detailed description of the invention that follows may be better
understood. Additional features and advantages of the invention
will be described hereinafter which form the subject of the claims
of the invention. It should be appreciated by those skilled in the
art that the conception and specific embodiment disclosed may be
readily utilized as a basis for modifying or designing other
structures for carrying out the same purposes of the present
invention. It should also be realized by those skilled in the art
that such equivalent constructions do not depart from the spirit
and scope of the invention as set forth in the appended claims. The
novel features which are believed to be characteristic of the
invention, both as to its organization and method of operation,
together with further objects and advantages will be better
understood from the following description when considered in
connection with the accompanying figures. It is to be expressly
understood, however, that each of the figures is provided for the
purpose of illustration and description only and is not intended as
a definition of the limits of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] For a more complete understanding of the present invention,
reference is now made to the following descriptions taken in
conjunction with the accompanying drawing, in which:
[0013] FIG. 1 is a graph showing the measured change in dioptor for
series of adjustable IOLs after an adjustment to the lenses was
made in vivo.
DETAILED DESCRIPTION OF THE INVENTION
[0014] The method of the invention is a means for evaluating the
biocompatibility and operability of adjustable optical implants
such as IOLs. The method involves placing the adjustable implant in
a non-human test subject, allowing wound healing to occur and then
determining if the implant poses safety or health risks to the
subject. The method further comprises evaluating the operability of
the lens in vivo. By operability is meant whether the implant can
be adjusted in the manner intended.
[0015] The term optical implant refers to any devices or structure
implanted in a living organism for the purpose of changing the
optical properties of the organisms eyes. Perhaps the most common
optical implant is an intraoccular lens the organisms natural lens
when the lens becomes damaged or no longer transmits light. As
described more fully below, adjustable optical implants are those
optical implants, such as IOLs whose properties can be manipulated
or adjusted post implantation by non-invasive measures. In the
preferred embodiment, the adjustable implants contain macromers
which are capable of inducing change in the implant when the
implant is exposed to an external stimulus.
[0016] Non-human test subject refers to a test subject, other than
a human being into which the optical element is implanted.
Typically this includes mammals which exhibit physiological
similarities to humans and includes rabbits, dogs, pigs and
chimpanzees or other simians. Of these, rabbits and pigs are most
preferred.
[0017] The first step of the method involves implanting the optical
implant into the test subject. In the case of an IOL this involves
first removing the existing lens using any standard technique such
as phaecoemulsification. Removal of the lens creates a cavity
within the capsular bag into which the IOL is then placed. The IOL
is inserted using standard techniques such as that described in
Clayman, Intraoccular Lens Implantation, 1985. Alternatively, the
IOL can be formed in situ in sets using a procedure describes in
Nishi, O. et al, 23 J. Cataract. Refract. Surg. 1548-53 (1997).
[0018] Once the implant is in place and the incision closed, the
wound created by the placement of the implant is allowed to heal.
This typically takes from 7 to 14 days.
[0019] Following wound healing the optical implants are then
evaluated for safety and if desired, operability. Safety evaluation
includes testing and observations for biocompatibility including
absence of infection and resistance to leaching of components and
degradation. Operability evaluation includes a determination as to
whether the implants perform as designed. In the case of implants
capable of adjustment or manipulation of function preferably
optical properties, this includes attempting adjust or manipulate
the optical properties of the implant in vivo and then evaluating
the implant to determine whether a change in the implant has
occurred and the nature and degree of the change.
[0020] In the preferred embodiment, the method of the invention
comprises a method for evaluating the safety and operability of
IOLs that are capable of adjustment or manipulation of their
optical properties by non-evasive success. In one embodiment the
IOLs contains macromers which, when exposed to an external
stimulus, induce changes in the optical properties of the IOL. In
the most preferred embodiment, the optical properties of the
implant are manipulated by stimulus induced polymerization of the
macromers causes changes in the refractive index of the implant,
the shape of the implant or both refractive index and shape. The
preferred stimulus used to induce polymerization of the macromers
is light with ultraviolet light most preferred.
[0021] To determine the operability of the IOLs after implanting
them in the test subject, the IOLs are exposed to an external
stimulus, such as ultraviolet light, in a prescribed pattern,
intensity, and duration. The pattern, intensity and duration of the
exposure is determined by the desired changes of optical properties
and the nature of the macromers and other components dispersed
throughout the IOL. Once the IOL has been exposed to the external
stimulus, it is left in the eye for further evaluation of the IOLs
safety and biocompatibility. This is done by observing the eye for
signs of infection, migration of material from the IOL and the like
which are indicator, that the lens is not biocompatible.
[0022] The IOLs are also examined to determine if the desired
change in optical properties has occurred. This can be accomplished
in several ways including physical examination of the lens in vivo
to see if the desired change in shape has occurred, use of
refractive techniques to see if the desired change in refractive
has occurred and explantation of the lens followed by examination
of the change in optical properties ex vivo. While these are the
preferred methods of evaluating the performance of the IOL, other
techniques are known.
[0023] One type of optical element which can be evaluated using the
novel method described herein are optical elements that are capable
of post operative adjustment of their properties. One class of
these elements is optical elements that comprise a first polymer
matrix and a macromer dispersed therein. The first polymer matrix
forms the optical element framework and is generally responsible
for many of its material properties. The macromer ("macromer") may
be a single compound or a combination of compounds that is capable
of stimulus-induced polymerization, preferably
photo-polymerization. As used herein, the term "polymerization"
refers to a reaction wherein at least one of the components of the
macromer reacts to form at least one covalent or physical bond with
either a like component or with a different component. The
identities of the first polymer matrix and the macromers will
depend on the end use of the optical element. However, as a general
rule, the first polymer matrix and the macromers are selected such
that the components that comprise the macromer are capable of
diffusion within the first polymer matrix. Put another way, a loose
first polymer matrix will tend to be paired with larger macromer
components and a tight first polymer matrix will tend to be paired
with smaller macromer components.
[0024] Upon exposure to an appropriate energy source (e.g., heat or
light), the macromer typically form a second polymer matrix in the
exposed region of the optical element. The presence of the second
polymer matrix changes the material characteristics of this portion
of the optical element to modulate its refraction capabilities. In
general, the formation of the second polymer matrix typically
increases the refractive index of the affected portion of the
optical element. After exposure, the macromer in the unexposed
region will migrate into the exposed region over time. The amount
of macromer migration into the exposed region is time dependent and
may be precisely controlled. If enough time is permitted, the
macromer components will re-equilibrate and redistribute throughout
optical element (i.e., the first polymer matrix, including the
exposed region). When the region is re-exposed to the energy
source, the macromer ("macromer") that has since migrated into the
region (which may be less than if the macromer composition were
allowed to re-equilibrate) polymerizes to further increase the
formation of the second polymer matrix. This process (exposure
followed by an appropriate time interval to allow for diffusion)
may be repeated until the exposed region of the optical element has
reached the desired property (e.g., power, refractive index, or
shape). At this point, the entire optical element is exposed to the
energy source to "lock-in" the desired lens property by
polymerizing the remaining macromer components that are outside the
exposed region before the components can migrate into the exposed
region. In other words, because freely diffusable macromer
components are no longer available, subsequent exposure of the
optical element to an energy source cannot further change its
power. FIG. 1 illustrates one inventive embodiment, refractive
index modulation (thus lens power modulation) followed by a lock
in.
[0025] The first polymer matrix is a covalently or physically
linked structure that functions as an optical element and is formed
from a first polymer matrix composition ("FPMC"). In general, the
first polymer matrix composition comprises one or more monomers
that upon polymerization will form the first polymer matrix. The
first polymer matrix composition optionally may include any number
of formulation auxiliaries that modulate the polymerization
reaction or improve any property of the optical element.
Illustrative examples of suitable FPMC monomers include acrylics,
methacrylates, phosphazenes, siloxanes, vinyls, homopolymers and
copolymers thereof. As used herein, a "monomer" refers to any unit
(which may itself either be a homopolymer or copolymer) which may
be linked together to form a polymer containing repeating units of
the same. If the FPMC monomer is a copolymer, it may be comprised
of the same type of monomers (e.g., two different siloxanes) or it
may be comprised of different types of monomers (e.g., a siloxane
and an acrylic).
[0026] In one embodiment, the one or more monomers that form the
first polymer matrix are polymerized and cross-linked in the
presence of the macromer. In another embodiment, polymeric starting
material that forms the first polymer matrix is cross-linked in the
presence of the macromer. Under either scenario the macromer
components must be compatible with and not appreciably interfere
with the formation of the first polymer matrix. Similarly, the
formation of the second polymer matrix should also be compatible
with the existing first polymer matrix. Put another way, the first
polymer matrix and the second polymer matrix should not phase
separate and light transmission by the optical element should be
unaffected.
[0027] As described previously, the macromer may be a single
component or multiple components so long as (i) it is compatible
with the formation of the first polymer matrix; (ii) it remains
capable to stimulus-induced polymerization after the formation of
the first polymer matrix; and (iii) it is freely diffusable within
the first polymer matrix. In preferred embodiments, the
stimulus-induced polymerization is photo-induced
polymerization.
[0028] The inventive optical elements have numerous applications in
the electronics and data storage industries. Another application
for the present invention is as medical lenses, particularly as
intraoccular lenses.
[0029] In general, there are two types of intraoccular lenses
("IOLs"). The first type of an intraoccular lens replaces the eye's
natural lens. The most common reason for such a procedure is
cataracts. The second type of intraoccular lens supplements the
existing lens and functions as a permanent corrective lens. This
type of lens (sometimes referred to as a phakic intraoccular lens)
is implanted in the anterior or posterior chamber to correct any
refractive errors of the eye. In theory, the power for either type
of intraoccular lenses required for emmetropia (i.e., perfect focus
on the retina from light at infinity) can be precisely calculated.
However, in practice, due to errors in measurement of corneal
curvature, and/or variable lens positioning and wound healing, it
is estimated that only about half of all patients undergoing IOL
implantation will enjoy the best possible vision without the need
for additional correction after surgery. Because prior art IOLs are
generally incapable of post-surgical power modification, the
remaining patients must resort to other types of vision correction
such as external lenses (e.g., glasses or contact lenses) or cornea
surgery. The need for these types of additional corrective measures
is obviated with the use of the intraoccular lenses of the present
invention.
[0030] The inventive intraoccular lens comprises a first polymer
matrix and a macromer dispersed therein. The first polymer matrix
and the macromer are as described above with the additional
requirement that the resulting lens be biocompatible.
[0031] Illustrative example of a suitable first polymer matrix
include: poly-acrylates such as poly-alkyl acrylates and
poly-hydroxyalkyl acrylates; poly-methacrylates such as poly-methyl
methaacrylate ("PMMA"), poly-hydroxyethyl methacrylate ("PHEMA"),
and poly-hydroxypropyl methacrylate ("HPMA"); poly-vinyls such as
poly-styrene and poly-vinylpyrrolidone ("PNVP"); poly-siloxanes
such as poly-dimethylsiloxane; poly-phosphazenes,and copolymers of
thereof. U.S. Pat. No. 4,260,725 and patents and references cited
therein (which we all incorporated herein by reference) provide
more specific examples of suitable polymers that may be used to
form the first polymer matrix.
[0032] In preferred embodiments, 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 crosslinking one
or more polymeric starting materials wherein each polymeric
starting material includes at least one crosslinkable group.
Illustrative examples of suitable crosslinkable groups include but
are not limited to hydride, acetoxy, alkoxy, amino, anhydride,
aryloxy, carboxy, enoxy, epoxy, halide, isocyano, olefinic, and
oxime. In more preferred embodiments, each 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 crosslinkable group. In other words, the terminal monomers
begin and end the polymeric starting material and include at least
one crosslinkable group as part of its structure. Although it is
not necessary for the practice of the present invention, the
mechanism for crosslinking the polymeric starting material
preferably is different than the mechanism for the stimulus-induced
polymerization of the components that comprise the Macromer. For
example, if the Macromer is polymerized by photo-induced
polymerization, then it is preferred that the polymeric starting
materials have crosslinkable groups that are polymerized by any
mechanism other than photo-induced polymerization.
[0033] An especially preferred class of polymeric starting
materials for the formation of the first polymer matrix is
poly-siloxanes (also known as "silicones") endcapped with a
terminal monomer which includes a crosslinkable group selected from
the group consisting of 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 material is
bis(diacetoxymethylsilyl)-polydimethylsilo- xane (which is
poly-dimethylsiloxane that is endcapped with a diacetoxymethylsilyl
erminal monomer).
[0034] The macromer that is used in fabricating IOLs is as
described above except that it has the additional requirement of
biocompatibility. The macromer is capable of stimulus-induced
polymerization and may be a single component or multiple components
so long as (i) it is compatible with the formation of the first
polymer matrix; (ii) it remains capable of stimulus-induced
polymerization after the formation of the first polymer matrix; and
(iii) it is freely diffusable within the first polymer matrix. In
general, the same type of monomers that is used to form the first
polymer matrix may be used as a component of the macromer. However,
because of the requirement that the macromer monomers must be
diffusable within the first polymer matrix, the macromers generally
tend to be smaller (i.e., have lower molecular weights) than the
monomers which form the first polymer matrix. In addition to the
one or more monomers, Macromer may include other components such as
initiators and sensitizers that facilitate the formation of the
second polymer matrix.
[0035] In preferred embodiments, the stimulus-induced
polymerization is photo-polymerization. In other words, the one or
more monomers that comprise the macromers 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 macromer
includes a photoinitiator (any compound used to generate free
radicals) ether alone or in the presence of a sensitizer. Examples
of suitable photinitiators include acetophenones (e.g.,
-substituted haloacetophenones, and diethoxyacetophenone);
2,4-dichloromethyl-1,3,5-triazines; benzoin methyl ether; and
o-benzoyl oximino ketone. Examples of suitable sensitizers include
p-(dialkylamino)aryl aldehyde; N-alkylindolyidene Check sp; and
bis[p-(dialkylamino)benzylidene] ketone.
[0036] Because of the preference for flexible and foldable IOLs, an
especially preferred class of macromer monomers is poly-siloxanes
endcapped with a termination siloxane moiety that includes a
photopolymerizable group. An illustrative representation of such a
monomer is
X--Y--X.sup.1
[0037] As described more fully below, adjustable optical implants
are those optical implants such as IOLs whose properties can be
manipulated or adjusted post implantation by non-invasive measures.
In the preferred embodiment, the adjustable implant's contain
macromers which are capable of inducing change in the implant when
the implant is exposed to an external stimulus.
[0038] 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. An illustrative example of Y include
1
[0039] 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 (primary, secondary, tertiary, cyclo), aryl, or
heteroaryl. In preferred embodiments, R.sup.1, R.sup.2, R.sup.3,
and R.sup.4 is a C.sup.1-C.sup.10 alkyl or phenyl. Because Macromer
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 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 and R.sup.4 is phenyl.
[0040] Illustrative examples of X and X.sup.1 (or X.sup.1 and X
depending on how the Macromer polymer is depicted) are 2
[0041] Respectively wherein:
[0042] R.sup.5 and R.sup.6 are independently each hydrogen, alkyl,
aryl, or heteroaryl; and
[0043] Z is a photopolymerizable group.
[0044] In preferred embodiments, R.sup.5 and R.sup.6 are
independently each a C.sub.1-C.sup.10 or phenyl and Z is a
photopolymerizable group that includes a moiety selected from the
group consisting of acrylate, allyloxy, connamoyl, methaacrylate,
stibenyl, and vinyl. In more preferred embodiments, R.sup.5 and
R.sup.6 is methyl, ethyl, or propyl and Z is a photopolymerizable
group that includes an acrylate or methacrylate moiety.
[0045] In especially preferred embodiments, an macromer monomer if
of the following formula 3
[0046] wherein X and X.sup.1 are the same and R.sup.1, R.sup.2,
R.sup.3, and R.sup.4 are as defined previously. Illustrative
examples of such Macromer monomers include
dimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyl
dimethylsilane group; dimethylsiloxane-methylpheny- lsiloxane
copolymer endcapped with a methacryloxypropyl dimethylsilane group;
and dimethylsiloxane endcapped with a methacryloxypropyldimethylsi-
lane group. 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 one class of inventive macromers.
Briefly, the method comprises contacting a cyclic siloxane with a
compound of the formula 4
[0047] in the presence of triflic acid wherein R.sup.5, R.sup.6,
and Z are as defined previously. 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 tetramer 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
methacryloxypropyl-dimethylsilane group, an especially preferred
macromer.
[0048] The adjustable IOLs may be fabricated with any suitable
method that results in a first polymer matrix with one or more
components which comprise the Macromer dispersed therein, and where
the Macromer is capable of stimulus-induced polymerization to form
a second polymer matrix. In general, the method for making an
inventive IOL is the same as that for making an inventive optical
element. In one embodiment, the method comprises:
[0049] mixing a first polymer matrix composition with a Macromer to
form a reaction mixture;
[0050] placing the reaction mixture into a mold;
[0051] polymerizing the first polymer matrix composition to form
said optical element; and
[0052] removing the optical element from the mold.
[0053] The type of mold that is used will depend on the optical
element being made. For example, if the optical element is a prism,
then a mold in the shape of a prism is used. Similarly, if the
optical element is an intraoccular lens, then an intraoccular lens
mold is used and so forth. As described previously, the first
polymer matrix composition comprises one or more monomers for
forming the first polymer matrix and optionally includes any number
of formulation auxiliaries that either modulate the polymerization
reaction or improve any property (whether or not related to the
optical characteristic) of the optical element. Similarly, the
Macromer comprises one or more components that together are capable
of stimulus-induced polymerization to form the second polymer
matrix. Because flexible and foldable intraoccular lenses generally
permit smaller incisions, it is preferred that both the first
polymer matrix composition and the Macromer include one or more
silicone-based or low T.sub.g acrylic monomers when the inventive
method is used to make IOLs.
[0054] Once the adjustable optical element has been formed, it is
then implanted in a non-human test subject. Implantation entails
removal of the existing lens by phaecoemulsification and extraction
of the lens debries. This is followed by implantation of the
element using standard surgical procedures.
[0055] After the eye has had sufficient time to heal, (1 to 2
weeks) the eye is then examined for evidence of inflammation. The
same time, operability testing can also be conducted.
[0056] Operability testing involves attempting to manipulate the
properties of the implant in vivo followed by an evaluation as to
whether the desired changes have occurred.
[0057] In the preferred embodiment, this entails exposing at least
a portion of the implant to an external stimulus so as to induce a
change in the properties of the implant. In one embodiment,
ultraviolet light is said to induce photopolymerization of
macromers in at least a portion of an adjustable IOL polymerization
of the macromers causes change in the shape of the IOL and/or the
refractive index of the IOL. The extent of the changes is then
evaluated to see if the desired optical properties have been
achieved.
[0058] Determination of biocompatibility can be accomplished either
in vivo or ex vivo or both. Physical examination of the eye can be
used to determine the presence of inflammation and their
biocompatibility. In some cases, however, it may be necessary to
explant the lens and conduct histopathological studies of the eye
tissue to determine biocompatibility.
[0059] The determination of operability requires that at least the
adjustment phase be done in vivo followed by examination of the
lens in vivo or ex vivo. In vivo examination of the lens can be
done using an autoretractometer or a Scheimpflug imaging device to
determine change in refraction and/or shape. Alternatively, the
lens may be explanted after an ajustment lens has been attempted
and the changes in the lens can be determined ex vivo.
EXAMPLE 1
[0060] Sterilized, adjustable IOLs were implanted in albino rabbit
eyes. After clinically following the eyes for one week, the rabbits
were sacrificed. The extracted eyes were evaluated, placed in
familiar and studied histopathologically. There was no evidence of
corneal toxicity, anterior segment inflammation or other signs of
lens toxicity.
EXAMPLE 2
[0061] A series of adjustable IOLs were prepared for implantation.
The IOLs comprised a silicon based polymer matrix with
dimethylsiloxane macromer dispersed therein. The safety and
operability of the lenses was evaluated in four rabbits. The
rabbits were first anesthetized and the existing lens was removed
using phaecoemulsification. The IOLs were then implanted into the
rabbits.
[0062] The rabbit eyes were exposed to ultraviolet light for 60 to
120 seconds to induce localized polymerization of macromer in the
center of the lens.
[0063] The next day, the rabbits were checked physically to
determine if any infection develop or if there was any evidence
that the lens was not biocompatible. No evidence of incompatibility
or infection was noted.
[0064] The lenses were then examined to determine if the desired
changes in optical properties had taken place. This was
accomplished by explanting the lenses and then evaluating the
change in lens power achieved. In this case the power of the lenses
increased an average of 0.72 diopters.
EXAMPLE 3
[0065] In this set of experiments, 16 adjustable lens were
implanted into albino rabbit eyes. The lenses were adjusted in vivo
to diopters of approximately -1.0, -0.5, +1.0 and 2.5 using
ultraviolet light. The lenses were then evaluated for
biocompatibility and operability by sacrificing the rabbits and
explanting the lenses. As shown in FIG. 1, four lenses showed a
change in diopters of -1.00,D four had a change in diopter of
-0.64D, three had a change in diopter of +0.98D and four had a
change of +2.68D.
[0066] Histopathological studies of the eyes showed no
inflammation. This indicated good biocompatibility for the
lens.
[0067] 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.
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