U.S. patent application number 13/282788 was filed with the patent office on 2012-02-23 for ocular lens.
Invention is credited to Leonard Pinchuk.
Application Number | 20120046743 13/282788 |
Document ID | / |
Family ID | 34681520 |
Filed Date | 2012-02-23 |
United States Patent
Application |
20120046743 |
Kind Code |
A1 |
Pinchuk; Leonard |
February 23, 2012 |
Ocular Lens
Abstract
An ocular lens has a refractive optics structure formed from a
polyisobutylene-based material and a glassy segment that is
non-reactive to ocular fluid and that maintains in vivo
transparency for a substantial time period. The material has a
central elastomeric polyolefinic block and thermoplastic end blocks
(such as a triblock polymer backbone comprising
polystyrene-polyisobutylene-polystyrene). The material is
preferably flexible such that the refractive optics structure can
be folded upon itself and introduced through a small scleral
incision. The lens device includes an optic portion and preferably
either an annular haptic element or one or more haptic elements
adapted to rest within a capsular bag formed by a surgical
procedure. A portion of the lens device may be loaded with at least
one therapeutic agent that interferes with proliferation of the
epithelial cells of the eye to protect against PCO.
Inventors: |
Pinchuk; Leonard; (Miami,
FL) |
Family ID: |
34681520 |
Appl. No.: |
13/282788 |
Filed: |
October 27, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12482857 |
Jun 11, 2009 |
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13282788 |
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11004538 |
Dec 3, 2004 |
7794498 |
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12482857 |
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60526965 |
Dec 5, 2003 |
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60526966 |
Dec 5, 2003 |
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Current U.S.
Class: |
623/6.43 ;
623/6.56 |
Current CPC
Class: |
A61L 2430/16 20130101;
A61F 2/1648 20130101; A61F 2/1613 20130101; A61F 9/0017 20130101;
A61L 27/16 20130101; A61L 27/54 20130101; A61L 27/16 20130101; A61L
2300/416 20130101; G02B 1/041 20130101; A61F 2/1629 20130101; G02B
1/041 20130101; G02B 1/041 20130101; A61F 2250/0067 20130101; C08L
23/22 20130101; C08L 25/08 20130101; C08L 53/02 20130101; C08L
23/22 20130101; A61L 27/16 20130101 |
Class at
Publication: |
623/6.43 ;
623/6.56 |
International
Class: |
A61F 2/16 20060101
A61F002/16 |
Claims
1-54. (canceled)
55. An ocular lens for use in an ocular environment comprising: a
deformable lens element; at least one haptic element extending
radially outward from said lens element, wherein said at least one
haptic element is coated with a polymer layer comprising
polyisobutylene and at least one therapeutic agent that interferes
with proliferation of epithelial cells in the ocular
environment.
56. An ocular lens according to claim 55, wherein: said lens
element is not coated with said polymer layer.
57. An ocular lens according to claim 55, wherein: said at least
one therapeutic agent is selected from the groups of cytostatic
agents and anti-migratory agents.
58. An ocular lens according to claim 55, wherein: said at least
one therapeutic agent comprises paclitaxel or an analog of
paclitaxel.
59. An ocular lens according to claim 55, wherein: said at least
one haptic element transfers accommodating forces applied by the
ciliary muscles of the ocular environment to said lens element in
order to vary radius of curvature of said lens element.
60. An ocular lens according to claim 55, wherein: said at least
one haptic element is adapted to rest within a capsular bag formed
by a surgical procedure.
61. An ocular lens according to claim 55, wherein: said at least
one haptic element extends radially outward from said lens element
from said lens element in a symmetric manner about the periphery of
said lens element.
62. An ocular lens according to claim 55, wherein: said ocular lens
is configurable into an arrangement where the lens element is
folded or rolled upon itself.
63. An ocular lens according to claim 55, wherein: said lens
elements has two and only two refractive surfaces extending
radially away from a central optical axis passing through the lens
element.
64. An ocular lens according to claim 55, wherein: said lens
element comprises a polyisobutylene-based polymer.
65. An ocular lens according to claim 64, wherein: said
polyisobutylene-based polymer is processed to remove salts
therefrom.
66. An ocular lens according to claim 64, wherein: said
polyisobutylene-based polymer further comprises a vinyl aromatic
polymer.
67. An ocular lens according to claim 66, wherein: said vinyl
aromatic polymer is selected from the group consisting of
polystyrene, and .alpha.-methylstyrene.
68. An ocular lens according to claim 64, wherein: said
polyisobutylene-based polymer further comprises a methacrylate
polymer.
69. An ocular lens according to claim 68, wherein: said
methacrylate polymer is selected from the group of a
methylmethacrylate polymer, a ethylmethacrylate polymer, and a
hydroxymethacrylate polymer.
70. An ocular lens according to claim 55, wherein: said lens
element is realized from a polymeric material having a general
block structure with a central elastomeric polyolefinic block and
thermoplastic end blocks.
71. An ocular lens according to claim 70, wherein: said polymeric
material has a triblock polymer backbone comprising
Poly(styrene-block-isobutylene-block-styrene).
72. An ocular lens according to claim 70, wherein: said polymeric
material has a general block structure selected from the group
consisting of: a) BAB or ABA, b) B(AB)n or A(BA)n, and c) X-(AB)n
or X-(BA)n; where A is an elastomeric polyolefinic block, B is a
thermoplastic block, n is a positive whole number and X is a
starting seed molecule.
73. An ocular lens according to claim 70, wherein: said polymeric
material comprises a copolymer selected from the group consisting
of a star-shaped block copolymer and multi-dendrite-shaped block
copolymer.
74. An ocular lens according to claim 55, wherein: said at least
one haptic element comprises an annular surface that surrounds and
extends radially outward from said lens element.
75. An ocular lens according to claim 74, wherein: said lens
element is configured to be substantially disposed along a plane
that is perpendicular to the optical axis of the ocular
environment, and said annular surface projects radially outward
from said optic portion at an angle relative to said plane, said
angle between 0 and 45 degrees.
76. An ocular lens according to claim 75, wherein: said angle is
between 10 and 20 degrees.
77. An ocular lens according to claim 75, wherein: said angle is 15
degrees.
78. An ocular lens device according to claim 55, wherein said lens
element has at least one of the following features: a) a front
convex surface; b) a flat back surface; c) a wall in its periphery
which is thicker than the minimum thickness of said lens element;
and d) a stepped wall structure at its periphery.
79. An ocular lens according to claim 55, wherein: said at least
one haptic element comprise a plurality of haptic elements that are
distributed symmetrically about the periphery of said lens
element.
80. An ocular device according to claim 55, wherein: said at least
one haptic element terminates at an edge offset radially from said
lens element, wherein the edge is operably disposed adjacent a
ciliary body of the ocular environment.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority from U.S.
Provisional Patent Application 60/526,965, filed Dec. 5, 2003 and
U.S. Provisional Patent Application 60/526,966, filed Dec. 5, 2003,
both herein incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates broadly to ocular lens devices. More
particularly, this invention relates to intraocular lens devices
that are surgically implanted within the capsular bag of a human
eye.
[0004] 2. State of the Art
[0005] The human eye has an anterior chamber between the cornea and
the iris, a posterior chamber behind the iris containing a
crystalline lens, a vitreous chamber behind the lens containing
vitreous humor, and a retina at the rear of the vitreous chamber.
The crystalline lens of a normal human eye has a lens matrix in
addition to a lens capsule attached about its periphery to the
ciliary muscle of the eye by zonules. This lens capsule has elastic
optically clear anterior and posterior membrane-like walls, which
are commonly referred by ophthalmologists as anterior and posterior
capsules, respectively. Between the iris and ciliary muscle is an
annular space called the ciliary sulcus.
[0006] The human eye possesses natural accommodation capability.
Natural accommodation involves relaxation and constriction of the
ciliary muscle by the brain to provide the eye with near and
distant vision. This ciliary muscle action is automatic and shapes
the natural crystalline lens to the appropriate optical
configuration for focusing the light rays entering the eye onto the
retina.
[0007] The human eye is subject to a variety of disorders which
degrade, or totally destroy, the ability of the eye to function
properly. One of the more common of these disorders involves
progressive clouding of the crystalline lens matrix resulting in
the formation of what is referred to as a cataract.
[0008] It is common practice to cure a cataract by surgically
removing the clouded crystalline lens and implanting an artificial
intraocular lens in the eye to replace the natural lens. The prior
art is replete with a vast assortment of intraocular lenses.
Examples of such lenses are described in the following patents:
U.S. Pat. Nos. 4,254,509, 4,298,996, 4,842,601, 4,963,148,
4,994,082, and 5,047,051. As is evident from the above patents,
intraocular lenses differ widely in their physical appearance and
arrangement.
[0009] Typically, cataracts are surgically removed by anterior
capsulotomy, which involves forming an incision in the sclera
beneath the cornea. Tooling is inserted through this incision and
manipulated to open the anterior capsule of the natural lens while
leaving intact a capsular bag. This capsular bag has an elastic
posterior capsule, an anterior capsular remnant or rim about the
anterior capsule opening and a capsular bag sulcus. The capsular
bag sulcus is located between the anterior capsule remnant and the
outer circumference of the posterior capsule. The capsular bag
remains attached about its periphery to the surrounding ciliary
muscle of the eye by the zonules of the eye. The lens matrix is
extracted from the capsular bag through the scleral incision by
phacoemulsification and aspiration (or in some other way). An
intraocular lens is then implanted through the scleral incision
such that it lies within the capsular bag.
[0010] A relatively recent and improved form of anterior
capsulotomy known as capsulorhexis forms a generally
circular-shaped opening through the anterior capsule by tearing the
anterior capsule of the natural lens capsule along a generally
circular tear line substantially coaxial with the lens axis and
removing the generally circular portion of the anterior capsule
surrounded by the tear line. If performed properly, capsulorhexis
provides a generally circular opening through the anterior capsule
of the natural lens capsule substantially coaxial with the axis of
the eye and surrounded circumferentially by a continuous annular
remnant or rim of the anterior capsule having a relatively smooth
and continuous inner edge bounding the opening.
[0011] Another anterior capsulotomy procedure, referred to as an
envelope capsulotomy, forms a generally arch-shaped opening through
the anterior capsule by cutting a horizontal incision in the
anterior capsule, then cutting two vertical incisions in the
anterior capsule intersecting and rising from the horizontal
incision, and finally tearing the anterior capsule along a tear
line having an upper upwardly arching portion which starts at the
upper extremity of the vertical incision and continues in a
downward vertical portion parallel to the vertical incision which
extends downwardly and then across the second vertical incision.
This procedure produces a generally arch-shaped anterior capsule
opening centered on the axis of the eye. The opening is bounded at
its bottom by the horizontal incision, at one vertical side by the
vertical incision, at its opposite vertical side by the second
vertical incision of the anterior capsule, and at its upper side by
the upper arching portion of the capsule tear.
[0012] Another capsulotomy procedure, typically referred to as can
opener capsulotomy, forms a generally circular-shaped opening
through the anterior capsule by piercing the anterior capsule at a
number of positions along a circular line substantially coaxial
with the axis of the eye and then removing the generally circular
portion of the anterior capsule circumferentially surrounded by the
line. This procedure produces a generally circular anterior capsule
opening substantially coaxial with the axis of the eye and bounded
circumferentially by an annular remnant or rim of the anterior
capsule.
[0013] Intraocular lenses differ widely in their physical
appearance and arrangement, yet generally have a central optical
region (or optic) and haptics which extend outward from the optic
and engage the interior of the eye in such a way as to support the
optic in a position centered on the axis of the eye. Intraocular
lenses also differ with respect to their accommodation capability,
and their placement in the eye. Accommodation is the ability of an
intraocular lens to accommodate, that is to focus the eye for near
and distant vision. Most non-accommodating lenses have single focus
optics, which focus the eye at a certain fixed distance only and
require the wearing of eyeglasses to change the focus. Other
non-accommodating lenses have bifocal optics which image both near
and distant objects on the retina of the eye. The brain selects the
appropriate image and suppresses the other image, so that a bifocal
intraocular lens provides both near vision and distant vision sight
without eyeglasses. Bifocal intraocular lenses, however, suffer
from the disadvantage that 20% of the available light is lost in
scatter, thereby providing lessened visual acuity. Newer
intraocular lenses, such as the intraocular lens described in U.S.
Pat. No. 6,685,741, achieve multifocal accommodation in response to
compressive forces exerted on the haptics of the lens. Such
compressive forces are derived from natural brain-induced
contraction and relaxation of the ciliary muscle and increases and
decreases in vitreous pressure. Such accommodating intraocular
lenses are surgically implanted within the evacuated capsular bag
of the patient's eye through the scleral incision and anterior
capsule opening in the capsular bag. The haptics of the lens are
situated within the outer perimeter of the capsular bag and are
designed to support the optics along the optical axis of the eye in
a manner that minimizes stretching of the capsular bag.
[0014] After surgical implantation of the intraocular lens in the
capsular bag of the eye, active endodermal cells on the posterior
side of the anterior capsule rim of the capsular bag causes fusion
of the rim to the elastic posterior capsule wall by fibrosis. This
fibrosis occurs about the haptics of the IOL in such a way that the
haptics are effectively "shrink-wrapped" by the fibrous tissue in
such a way as to form radial pockets in the fibrous tissue. These
pockets contain the haptics with their outer ends positioned within
the outer perimeter of the capsular bag. The lens is thereby
fixated with the capsular bag with the lens optic aligned with the
optical axis of the eye. The anterior capsule rim shrinks during
fibrosis, and this shrinkage combined with the shrink-wrapping of
the haptics causes some radial compression of the lens in a manner
which tends to move the lens optic along the optical axis of the
eye. The fibrosed, leather-like anterior capsule rim prevents
anterior movement of the optic and urges the optic rearwardly
during fibrosis. Accordingly, fibrosis induced movement of the
optic occurs posteriorly to a distant vision position in which
either (or both) the optic and inner ends of the haptics press
rearwardly against the elastic posterior capsule wall, thereby
stretching the posterior capsule wall rearwardly.
[0015] With time, depending on the rearward pressure of the
intraocular lens on the posterior capsule wall as well as other
factors (such as lens material, lens geometry, angulation,
sharpness, wrinkles in the posterior capsule wall, etc), epithelium
cells can migrate between the posterior capsule wall and the lens
and reside and multiply in these spaces. Excessive build up of the
cells in this area can lead to opacification of the optic. This
opacification, commonly referred to as posterior capsule
opacification (PCO), causes clouding of vision and can lead to
blurring and possibly total vision loss. The process of PCO is slow
and clinical changes often take one to two years to become
apparent. PCO is typically treated by YAG laser capsulotomy.
However, in terms of health economics, PCO is very expensive to
treat.
[0016] Special care must also be taken that the material of the
lens optic maintains transparency after it has been implanted
within the eye and subject to ocular fluids. This characteristic is
referred to herein as "in vivo transparency" or "in vivo
transparent". Any significant clouding of the lens optic due to its
interaction with ocular fluids can lead to blurring and possibly
total vision loss in a manner similar to PCO. In U.S. Pat. No.
6,102,939, the inventor describes the crack resistance and
biostability of a prosthesis implanted in vivo wherein the
prosthesis formed from a polyolefinic copolymer material having a
triblock polymer backbone comprising
polystyrene-polyisobutylene-polystyrene, which is herein referred
to as "SIBS", while also mentioning the desirability of long term
elastomers for use in intraocular lenses as well as a long list of
other applications (e.g., vascular grafts, endoluminal grafts,
finger joints, indwelling catheters, pacemaker lead insulators,
breast implants, hear valves, etc.). However, this patent fails to
address important considerations (such as in vivo transparency)
with regard to the suitability of the SIBS material for use in the
ocular environment.
[0017] Modern intraocular lenses are made flexible where they can
be folded in half to enable placement in the capsular bag through
the scleral incision. However, such lenses typically have
relatively lower indices of refraction, and thus such intraocular
lenses are required to be thicker to provide the desired
magnification characteristics of the intraocular lens. More
particularly, the prior art foldable intraocular lenses are
typically made of a silicone-based polymer with an index of
refraction of 1.3 to 1.4, or made from an acrylic material with an
index of refraction of 1.46. Such refractive indices are relatively
low (for example, PMMA which is typically used for a rigid IOL has
a refractive index of 1.49). Thus, such intraocular lenses are
required to be thicker to provide the desired magnification
characteristics of the intraocular lens. One skilled in the art
understands that the magnification of a lens is dependent upon
three values: i) radii of curvature; ii) index of refraction; and
iii) thickness of the lens. Thus, for any given lens thickness, a
greater index of refraction provides a greater degree of
magnification. Alternatively, for any desired magnification, the
higher the index of refraction enables the lens to be thinner. The
thinner the lens, the smaller it can be folded or rolled. This
allows the scleral incision to be made smaller and possibly avoids
the use of sutures in closing the scleral incision. Suturing the
scleral incision is disadvantageous because the scleral incision
site, if not sutured properly, becomes a site of infection and
leakage of aqueous fluid. Moreover, if the sutures are too lose or
tight, astigmatism can form due to distortion of the cornea. On the
other hand, if the scleral incision is small (e.g., less than a 2
mm slit), the incision will close on its own without the use of
sutures. In addition, the thinner the lens, the more its radius of
curvature can be deformed and/or axial displaced by changing
tension in the anterior capsule by muscular contraction, thereby
providing for enhanced accommodation after implantation.
[0018] Modern intraocular lens also act as a spectral filters that
block out ultra-violet (UV) light that may burn the retina. Such UV
light blocking capability is typically provided by additives that
absorb UV radiation. Such additives are generally molecules that
contain aromatic groups. These additives can migrate out of the
polymeric material of the lens and cause toxic reactions.
[0019] Thus, there remains a need in the art to provide an
intraocular lens device that is realized from a flexible
biocompatible material that maintains in vivo transparency and has
a relatively high index of refraction. Such features provide for a
foldable intraocular lens that requires a small incision in the
sclera, and thus provides for more effective healing of the eye as
noted above. The relatively high index of refraction also provides
for an intraocular lens with improved magnification
capabilities.
[0020] There is also a need in the art to provide an intraocular
lens device that is realized from a biocompatible material with
ultra-violet light blocking capability that does not risk toxic
reaction in the eye.
[0021] There is also need in the art to provide an intraocular lens
device that inhibits epithelium cell migration and multiplication
to thereby protect against PCO.
[0022] Several methods of manufacturing flexible, biocompatible
intraocular lens devices are known, such as injection molding, spin
casting, compression molding and transfer molding. These methods
typically employ a polished stainless steel mold cavity that is
formed in a geometry that achieves the desired curvature. Several
significant problems have been associated with these molding
techniques. One problem is that the stainless steel mold requires
cleaning between molding cycles, which increases the labor costs
and production costs associated with the finished product. Another
problem is that steel molds typically have small gaps between the
mold halves that allow "flash" to form in the gaps during the
molding operation. Flash is unwanted material attached to the mold
parting line on the finished product. This flash material must be
removed from the finished product, which again increases the labor
costs and production costs associated with the finished
product.
[0023] Thus, there remains a need in the art to provide improved
techniques for the manufacture of flexible, biocompatible
intraocular lens devices which are less expensive than the prior
art manufacturing techniques.
SUMMARY OF THE INVENTION
[0024] It is therefore an object of the invention to provide an
ocular lens device that is realized from a flexible biocompatible
material that maintains in vivo transparency and has a relatively
high index of refraction.
[0025] It is another object of the present invention to provide
such an ocular lens device that is suitable as an intraocular
implant that requires a small incision in the sclera of the eye,
and thus provide for more effective healing of the eye
post-operatively as noted above.
[0026] It is a further object of the present invention to provide
an ocular lens device that provides improved magnification
capabilities.
[0027] It is yet another object of the present invention to provide
an ocular lens device that is realized from a biocompatible
material with ultra-violet light blocking capability that does not
risk toxic reaction in the eye.
[0028] It is another object of the present invention to provide an
intraocular lens device that inhibits epithelium cell migration and
multiplication to thereby protect against PCO.
[0029] It is a further object of the present invention to provide a
method (and corresponding apparatus) for the manufacture of the
improved intraocular lens devices described herein.
[0030] It is yet another object of the present invention to provide
a method (and corresponding apparatus) for the manufacture of
intraocular lens devices which is less expensive than the prior art
manufacturing techniques.
[0031] In accord with these objects, which will be discussed in
detail below, an ocular lens device includes a refractive optics
structure formed from a polyisobutylene-based material and a glassy
segment. Preferably, the material has a central elastomeric
polyolefinic block and thermoplastic end blocks (such as a triblock
polymer backbone comprising
polystyrene-polyisobutylene-polystyrene). The material of the
refractive optics structure maintains in vivo transparency during
implantation in its intended ocular environment for a substantial
period of time. The material of the lens device is flexible such
that it can be folded or rolled upon itself, which allows for the
scleral incision to be made small (e.g., less than a 2 mm slit) and
thus enables more effective healing of the scleral incision without
sutures. The lens device preferably includes an optic portion and
at least one haptic element that are adapted to rest within a
capsular bag formed by a surgical procedure. The at least one
haptic element supports the optic portion within the capsular bag.
Preferably, the material of the refractive optics structure
inherently blocks ultra-violet light without the addition of any
additives.
[0032] According to one embodiment of the invention, the lens
device may have a plurality of haptic elements that project
radially away from the optic portion.
[0033] According to another embodiment of the invention, the lens
device may have an annular haptic element that extends radially
outward from the optic portion. The annular haptic element projects
radially outward from the optic portion at an angle relative to the
plane of the optic region at an angle between 0 and 45 degrees, and
preferably at an angle between 10 and 20 degrees, and most
preferably at an angle of 15 degrees. The optic portion preferably
has a front convex surface and a flat back surface in addition to a
stepped wall structure at its periphery.
[0034] According to yet another embodiment of the invention, the
material of the lens device may be loaded with therapeutic drugs
that interfere with cell proliferation, which is advantageous in
intraocular applications in order to protect against PCO.
[0035] According to another embodiment of the invention, the in
vivo transparent nature of the material of the refractive optics
structure is accomplished by washing the polyisobutylene-based
polymer to substantially remove remnant salts, and processing the
polyisobutylene-based polymer at a controlled temperature(s) and/or
a controlled processing time(s) to form a refractive optics
structure. In one methodology, the refractive optics structure is
formed by processing the polyisobutylene-based polymer material at
controlled temperatures that are significantly less that the
melting point of the polyisobutylene-based polymer. In another
methodology, the refractive optics structure is formed by rapidly
heating the polyisobutylene-based polymer to a temperature at or
near its melting point, utilizing the resultant polymer melt to
form the refractive optics structure in a closed mold, and then
rapidly cooling the polymer/mold back to room temperature.
[0036] According to yet another embodiment of the invention, the
lens device changes its radius of curvature or position in response
to changes in tension of the lens capsule and/or from changes in
pressure in the vitreous.
[0037] Additional objects and advantages of the invention will
become apparent to those skilled in the art upon reference to the
detailed description taken in conjunction with the provided
figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] FIG. 1 is an illustration showing anatomic details of the
human eye in addition to the implantation of an intraocular lens
device in accordance with the present invention.
[0039] FIG. 2 is a front view of an exemplary embodiment of an
intraocular lens device in accordance with the present
invention.
[0040] FIGS. 3 and 4 illustrate the operation of the intraocular
lens device of FIG. 2 to provide for accommodation of the eye in
response to contraction and relaxation of the ciliary muscles of
the eye.
[0041] FIG. 5 is a front view of an alternate embodiment of an
intraocular lens device in accordance with the present
invention.
[0042] FIGS. 6A, 6B and 6C illustrate different annular haptic
designs that can be utilized in the embodiment of FIG. 5.
[0043] FIGS. 7 and 8 are front views of alternate embodiments of an
intraocular lens device in accordance with the present
invention.
[0044] FIGS. 9A and 9B illustrate the operation of an alternate
embodiment of intraocular lens device in accordance with the
present invention in providing for accommodation of the eye in
response to contraction and relaxation of the ciliary muscles of
the eye.
[0045] FIG. 10 is a cross-sectional schematic view of a centrifugal
casting apparatus for use in fabricating an ocular lens device in
accordance with the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0046] Turning now FIG. 1, there is shown a human eye 10 from which
the natural crystalline lens matrix was previously removed by a
surgical procedure involving an anterior capsulotomy, in this case
a continuous tear circular tear capsulotomy, or capsulorhexis. The
natural lens comprises a lens capsule having elastic anterior and
posterior walls, which are referred herein as anterior and
posterior capsules, respectively. As mentioned earlier, continuous
tear circular capsulotomy, or capsulorhexis, involves making an
incision in the sclera of the eye. Tooling is inserted through this
incision and manipulated to tear the anterior capsule along a
generally circular tear line in such a way as to form a relatively
smooth-edged circular opening in the center of the anterior
capsule. The cataract is removed from the natural lens capsule
through the scleral incision. After completion of this surgical
procedure, the eye includes an optically clear anterior cornea 12,
an opaque sclera 14, a retina 16, an iris 18, a capsular bag 20
behind the iris, and a vitreous cavity 21 behind the capsular bag
filled with the gel-like vitreous humor. The capsular bag 20 is the
structure of the natural lens of the eye which remains intact after
the capsulorhexis has been performed and the natural lens matrix
has been removed. The capsular bag 20 includes an annular anterior
capsular remnant or rim 22 and an elastic posterior capsule 24
which are joined along the perimeter of the bag 20 to form an
annular crevice-like bag structure between the capsular rim 22 and
posterior capsule 24. The capsular rim 22 is the remnant of the
anterior capsule of the natural lens which remains after
capsulorhexis has been performed on the natural lens. This rim
circumferentially surrounds a central, generally round anterior
opening 26 (capsulotomy) in the capsular bag through which the
natural lens matrix was previously removed from the natural lens.
The capsular bag 20 is secured about its perimeter to the ciliary
muscle of the eye by zonules 30. Eye 10 also includes an optical
axis OA-OA that is an imaginary line that passes through the
optical center of intraocular lens 32. An optical axis OA in the
human eye 10 is generally perpendicular to a portion of cornea,
natural lens and retina.
[0047] Natural accommodation in a normal human eye involves
contraction and relaxation of the ciliary muscle of the eye by the
brain in response to looking at objects at different distances.
Ciliary muscle relaxation, which is the normal state of the muscle,
positions and shapes the human crystalline lens for distant vision.
Ciliary muscle contraction positions and shapes the human
crystalline lens for near vision. The brain-induced change from
distant vision to near vision is referred to as accommodation.
[0048] An accommodating intraocular lens 32 according to the
present invention is implanted through the scleral incision into
the capsular bag 20 of the eye 10. The intraocular lens 32 replaces
and performs the accommodation function of the removed natural
crystalline lens. As illustrated in FIG. 2, the intraocular lens 32
of the present invention includes an optic portion 34 with an outer
peripheral edge 36. Three haptic elements 40A, 40B, 40C
(collectively, 40) project radially outward from the peripheral
edge 36 of optic portion 34. The haptic elements 40A, 40B, 40C are
preferably integrally formed with and permanently connected to the
outer peripheral edge 36 of optic portion 34. The haptic elements
40A, 40B, 40C include respective end portions 42A, 42B, 42C that
are adapted to rest in and engage the annular capsular bag 20,
which is disposed between the capsular rim 22 and posterior capsule
24. The end portions 42A, 42B, 42C are held in place through
compressive forces exerted by the inner surfaces of the capsular
bag 20 thereon. In this position, the optic portion 34 is
substantially aligned with the optical axis OA of the eye, the
posterior side of the optical portion 34 faces the elastic
posterior capsule 24, and the end portions 42A, 42B, 42C fit
snuggly within the capsular bag 20 at the radially outer perimeter
of the bag, which prevents decentration of the intraocular lens
32.
[0049] The haptic elements 40A, 40B, 40C also include hinge
portions 44A, 44B, 44C which join the end portions of the haptic
elements to the optic portion 34. The haptic elements 40A, 40B, 40C
are flexible about the respective hinge portions 44A, 44B, and 44C
anteriorly and posteriorly relative to the optic portion 34. The
hinge portions 44A, 44B, 44C may be formed by narrowing structures
as shown. Alternatively, the hinged portions may be formed by
grooves or other structural features of the haptic elements 40A,
40B, and 40C. In this manner, the haptic elements 40A, 40B, 40C are
adapted to flex about respective axes 46A, 46B, 46C such that the
optic portion 34 moves generally along the optical axis OA of eye
10, thereby achieving axial displacement of the optic portion 34 in
a direction along optical axis OA. By designing such flexion
characteristic into the haptic elements 40A, 40B, 40C, the
intraocular lens 32 allows an eye to achieve multifocal visual
imaging without the aid of eyeglasses.
[0050] In alternate embodiments, the haptic elements 40 are adapted
to transmit radial forces applied to rim of capsular bag by ciliary
muscle contraction and relaxation to the optic portion 34, whose
radius of curvature (e.g., diopter) changes in response thereto. In
such embodiments, the haptic elements 40 are preferably adapted
such that the optic portion 34 is not substantially displaced along
the optical axis OA of eye 10 in response to such ciliary muscle
contraction and relation. By designing such deformation
characteristics into the haptic elements 40 and the optic portion
34, the intraocular lens 32 allows the eye to achieve multifocal
visual imaging without the aid of eyeglasses.
[0051] According to the preferred embodiment of the present
invention, the intraocular lens 32 (or a portion of the lens 32
such as the optic portion 34) is formed from a polyolefinic
copolymer material having a triblock polymer backbone comprising
polystyrene-polyisobutylene-polystyrene, which is herein referred
to as "SIBS". Non-cross linked high molecular weight
polyisobutylene (PIB) is a soft putty-like material with a Shore
hardness less than 20 A. When copolymerized with polystyrene, it
can be made at hardnesses ranging up to the hardness of
polystyrene, which has a Shore hardness of 100 D. Thus, depending
on the relative amounts of styrene and isobutylene, the SIBS
material can have a range of hardnesses from as soft as Shore 10 A
to as hard as Shore 100 D. In this manner, the SIBS material can be
adapted to have the desired elastomeric and hardness qualities. In
the preferred embodiment, the SIBS material for lens 32 (including
the optic portion 34 and the haptic elements) is flexible such that
it can be folded and/or rolled upon itself, which minimizes the
size of the scleral incision required for implantation and enables
healing of the scleral incision without sutures. It therefore
provides for more effective healing of the eye post-operatively as
noted above. After inserting the lens 32 in its folded state
through the scleral incision, the lens 32 is unfolded and
positioned such that it is supported within the capsulary bag. The
optic portion 34 and the haptic elements can be realized from the
same SIBS material, a different SIBS material (e.g., a SIBS
material with a different hardness quality), or from different
biocompatible polymers altogether. When formed from different
materials, the haptic elements can be insert-molded, adhered with
an adhesive or heat or sonic welded to the optics portion 34 of the
lens 32. Details of the SIBS material is set forth in U.S. Pat.
Nos. 5,741,331; 6,102,939; 6,197,240; 6,545,097, which are hereby
incorporated by reference in their entirety.
[0052] The SIBS material of the intraocular lens 32 may be
polymerized under control means using carbocationic polymerization
techniques such as those described in U.S. Pat. Nos. 4,276,394;
4,316,973; 4,342,849; 4,910,321; 4,929,683; 4,946,899; 5,066,730;
5,122,572; and Re 34,640, each herein incorporated by reference in
its entirety. The amount of styrene in the copolymer material is
preferably between about 1 mole percent to 30 mole %. The styrene
and isobutylene copolymer materials are preferably copolymerized in
solvents.
[0053] In accord with another aspect of the invention, it is
expected that alternative polymeric materials are suitable for the
practice of the present invention. Such alternative polymeric
materials preferably include polyisobutylene-based material capped
with a glassy segment. The glassy segment provides hard domains for
the elastomeric polyisobutylene and is non-reactive in the ocular
environment (e.g., it will not react with the fluid of the eye).
The glassy segment preferably does not contain any cleavable group
which will release in the presence of body fluid inside the human
eye and cause toxic side effects. Moreover, the
polyisobutylene-based material and glassy segment preferably avoid
cell encapsulation in the ocular environment. The glassy segment
can be a vinyl aromatic polymer (such as polystyrene,
.alpha.-methylstyrene, or a mixture thereof), or a methacrylate
polymer (such as methylmethacrylate, ethylmethacrylate,
hydroxymethalcrylate, or a mixture thereof). Such materials
preferably have a general block structure with a central
elastomeric polyolefinic block and thermoplastic end blocks. Even
more preferably, such materials have a general structure: [0054]
BAB or ABA (linear triblock), [0055] B(AB)n or A(BA)n (linear
alternating block), or [0056] X-(AB)n or X-(BA)n (includes diblock,
triblock and other radial block copolymers), [0057] where A is an
elastomeric polyolefinic block, B is a thermoplastic block, n is a
positive whole number and X is a starting seed molecule. Such
materials may be star-shaped block copolymers (where n=3 or more)
or multi-dendrite-shaped block copolymers.
[0058] During a post-operative healing period on the order of two
to three weeks following surgical implantation of the lens 32 in
the capsular bag 20, epithelial cells cause fusion of the inner
surface of the rim 22 to the posterior capsule 24 by fibrosis. In
the case that the haptic elements 40A, 40B, 40C are formed from a
material that avoids cell encapsulation in the ocular environment,
the non-encapsulating nature of the material causes the fibrosis to
occur around the haptic elements 40A, 40B, 40C in such a way that
the haptic elements are loosely wrapped by the capsular bag 20 to
form pockets in the fibrosed material. These pockets cooperate with
the haptic elements 40A, 40B, 40C to position and center the lens
32 in the eye. Ciliary muscle induced flexing of the lens 32 during
fibrosis can be resisted or prevented by using a cyclopegic and/or
by wrapping sutures around the hinge portions 44A, 44B, 44C.
Removal of these sutures after completion of fibrosis may be
accomplished by using sutures that are either absorbable in the
fluid within the eye or by using sutures made of a material, such
as nylon, which can be removed by a laser.
[0059] Natural accommodation in a normal human eye involves shaping
of the natural crystalline lens by automatic contraction and
relaxation of the ciliary muscle of the eye by the brain to focus
the eye at different distances. Ciliary muscle relaxation shapes
the natural lens for distant vision. Ciliary muscle contraction
shapes the natural lens for near vision. The accommodating
intraocular lens 32 is adapted to utilize this same ciliary muscle
action, the fibrosed capsular rim 22, the elastic posterior capsule
24, and the vitreous pressure within the vitreous cavity 21 to
effect accommodation movement of the lens optic 34 along the optic
axis of the eye between its distant vision position of FIG. 3 to
its near vision position of FIG. 4. Thus, when looking at a distant
scene, the brain relaxes the ciliary muscles. Relaxation of the
ciliary muscles stretches the capsular bag 20 to its maximum
diameter and its fibrosed anterior rim 22 to the taut
trampoline-like condition or position discussed above. The taut rim
deflects the optics portion 34 rearwardly to its posterior distant
vision position of FIG. 3 in which the elastic posterior capsule 24
is stretched rearwardly by the optics portion 34 and thereby exerts
a forward biasing force on the lens 32. When looking at a near
scene, such as a book when reading, the brain constricts or
contracts the ciliary muscle. This ciliary muscle contraction
increases the vitreous cavity pressure and relaxes the capsular bag
20 and particularly its fibrosed capsular rim 22. The relaxed
capsular bag 20 exerts opposing endwise compression forces on the
ends of the haptic elements 40A, 40B, and 40C with resultant
endwise compression of the lens 32. Such relaxation of the capsular
rim permits the rim to flex forwardly and thereby enables the
combined forward bias force exerted on the lens by the rearwardly
stretched posterior capsule and the increased vitreous cavity
pressure to push the lens forwardly to its near vision position of
FIG. 4. Intermediate vision positions between the far vision
position of FIG. 3 and the near vision position of FIG. 4 are
obtained by relaxation and/or contraction of the ciliary muscles in
a manner similar to that described above, which allows the eye to
focus at different distances.
[0060] In alternate embodiments, such as those described below with
respect to FIGS. 9A and 9B, accommodation is provided by changing
the radius of curvature of the optic portion of the lens without
substantially changing the position of the lens device along the
optical axis (OA) of the eye. In these embodiments, relaxation of
the ciliary muscles (which is accomplished by the brain when
looking at a distant scene) stretches the capsular bag 20 and its
fibrosed anterior rim 22 to the taut trampoline-like condition or
position discussed above. The taut rim applies radial tension to
the haptic elements 40 and optics portion 34 of the lens device 32,
which causes the radius of curvature of the optic portion 34 to
increase (FIG. 9A). When looking at a near scene, the brain
constricts or contracts the ciliary muscle. This ciliary muscle
contraction increases the vitreous cavity pressure and relaxes the
capsular bag 20 and particularly its fibrosed capsular rim 22. The
relaxed capsular bag 20 releases the radial forces on the haptic
elements 40 and the optic portion 34 of the lens device 32 such
that the radius of curvature of the optic portion 34 decreases
(FIG. 9B). These operations provide for accommodation which allows
the eye to focus at different distances.
[0061] The IOL of the present invention can also be realized by
different haptic designs, such as those that utilize two haptics,
four haptics, and ring haptics as is well known in the art. FIG. 5
illustrates a top view of an IOL 32' with an optic portion 34' and
an annular haptic element 40'. Cross-sections for different
embodiments are shown in FIGS. 6A-6C. The front and back surfaces
of optic portion 34' can be of any diopter (curvature) necessary to
provide the desired correction for the patient. For example, the
front surface of the optic portion 34' may be convex as shown in
FIGS. 6A-C or possibly concave (not shown). The back surface of the
optic portion 34' is preferably flat as shown in FIGS. 6A-6C, but
it may be concave or convex to add or subtract magnification.
[0062] As shown in FIGS. 6A-6C, the angle .theta. of the annulus of
the haptic element 40' relative to the plane of the optic portion
34' (which is disposed substantially perpendicular to the optical
axis of the eye) is between 0 and 45 degrees, and more preferably
between 10 and 20 degrees, and most preferably 15 degrees. The IOL
34' is formed from a flexible material, such as the SIBS material
described above, such that it can be folded and/or rolled upon
itself, which minimizes the size of the scleral incision required
for implantation and enables healing of the scleral incision
without sutures. It therefore provides for more effective healing
of the eye post-operatively as noted above. After inserting the IOL
34' in its folded state through the scleral incision, the IOL 34'
is unfolded and positioned such that it is supported within the
capsulary bag. When placed in the capsular bag, the annular haptic
element 40' is adapted to rest in and engage the annular capsular
bag 20, which is disposed between the capsular rim 22 and posterior
capsule 24. The peripheral portion 42' of the annular haptic
element 40' is held in place through compressive forces exerted by
the inner surfaces of the capsular bag 20 thereon. In this
position, the optic portion 34' is substantially aligned with the
optical axis OA of the eye, the posterior side of the optical
portion 34' faces the elastic posterior capsule 24, and the
peripheral portion 42' of the annular haptic element 40' fits
snuggly within the capsular bag 20 at the radially outer perimeter
of the bag, which prevents decentration of the intraocular lens
32'. This configuration is similar to the configuration shown in
FIG. 1.
[0063] As shown in FIGS. 6A and 6B, the outer edge of the optic
portion 34' may be defined by a step 60, which serves as a boundary
wall to prevent cells from migrating from the periphery of the lens
32' and over the area of the optic portion 34'. Note however that
the step 60 may be omitted as shown in the embodiment of FIG. 6C,
especially if antiproliferating or antimigration agents are used to
prevent cell multiplication and migration under the lens.
[0064] The embodiment of FIG. 6B is similar to the embodiment of
FIG. 6A, except that the thickness (i.e., the distance between
front and back surfaces) of the optic portion 34' is smaller in the
embodiment of FIG. 6B, which should allow the optic portion 34' to
be folded or rolled smaller. In addition, the flat surface of the
lens can be curved to provide more magnification if desired.
Alternate embodiments with annular haptic designs are shown in
FIGS. 7 and 8.
[0065] In the embodiment of FIG. 7, a plurality of holes 44 are
formed about the annular haptic 40''. These holes preferably enable
fluid or viscoelastic (if used) migration between the front and
back of the lens 32'' as well as aid in fixation of the lens to the
annular capsular bag by cellular ingrowth. More particularly,
during a post-operative healing period on the order of two to three
weeks following surgical implantation of the lens 32'' in the
capsular bag 20, epithelial cells cause fusion of the inner surface
of the rim 22 to the posterior capsule 24 by fibrosis. In the case
that the annular haptic element 40'' is formed from the SIBS
material, the non-encapsulating nature of the SIBS material causes
the fibrosis to occur through the holes 44 in such a way that the
haptic element 40'' is wrapped tightly by the capsular bag. Ciliary
muscle induced flexing of the lens 32'' during fibrosis can be
resisted or prevented by using a cyclopegic and/or by other
means.
[0066] In the embodiment of FIG. 8, the annular haptic element
40''' has a plurality of radial cuts 46 formed therein. The radial
cuts 46 extend radially from the central optic portion 34''' to the
periphery of the annular haptic element 40''' as shown. The radial
cuts 46 better enable proper placement into the capsular bag.
[0067] In the embodiments of FIGS. 5-8, the circular nature of the
haptic annulus helps force the lens against the posterior capsule
24 and helps prevent wrinkles from forming in the capsule and
channels for cell migration (which can lead to PCO). In addition,
the force of the annular haptic element against the lens capsule is
such that ciliary muscle contraction and relaxation causes movement
of the optic region along the optical axis by puckering of the lens
(in other words, changing the angle .theta.). In this manner, the
annular haptic provides for accommodation between a far vision
position and near vision position in a manner similar to that
described above with respect to FIGS. 3 and 4, and thus allows the
eye to focus at different distances without the need for reading
glasses. Alternatively, the annular haptic element can be adapted
such that ciliary muscle contraction and relaxation causes the
optic portion of the lens to bow and change its radius of curvature
as shown in FIGS. 9A and 9B.
[0068] In another embodiment shown in FIGS. 9A and 9B, an
accommodating lens device 32'''' is shown having an optic portion
34'''' and haptic elements 40'''' wherein the thickness of the
haptic elements 40'''' is greater than the thickness of the optic
portion 34''''. Alternatively, the modulus of elasticity of the
material of haptic elements 40'''' may be greater than the modulus
of elasticity of the material of the optic portion 34''''. In this
configuration, when tension is applied radially, as depicted by the
arrows 901 of FIG. 9A, the radius of curvature of the optic portion
34'''' increases. When the tension is released, the optic portion
34'''' reverts back to its natural state with a smaller radius of
curvature as shown in FIG. 9B. Such operations provide for change
in diopter of the optic portion 34'''' and accommodation of the
lens device. By forming the optic portion 34'''' with a smaller
thickness (or smaller modulus of elasticity) that the haptic
elements 40'''', the response (e.g., change in diopter) of the
optic portion 34'''' to the radial tension forces applied thereto
is maximized, which allows for a greater range of accommodation of
the eye. The smaller thickness optic portion 34'''' may also allow
for the scleral incision to be made smaller and thus provide for
more effective healing of the eye post-operatively as noted
above.
[0069] It was surprisingly found that the polyisobutylene-based
material of the intraocular lens 32 as described herein has a high
index of refraction ranging from 1.52 to 1.54. This relatively high
index of refraction provides for improved magnification
capabilities, and also allows the lens 23 to be thinner for a given
magnification factor. Decreasing the thickness of the lens 23 is
advantageous because it allows the scleral incision to be made
smaller and thus provide for more effective healing of the eye
post-operatively as noted above. It also provides for improved
response to ciliary muscle contraction and relaxation as noted
above.
[0070] It was also surprisingly found that the SIBS material of the
intraocular lens 32 effectively blocks ultra-violet light. More
particularly, the aromatic styrene groups of the
polystyrene-polyisobutylene-polystyrene SIBS material are natural
intrinsic filters of ultra-violet light. Thus, the exemplary SIBS
material of the intraocular lens 32 may advantageously block
ultra-violet light without the need for potentially toxic
additives.
[0071] The polymeric intraocular lens 32 of the present invention
can be loaded with therapeutic drugs that release over time and
interfere with the ability of the epithelial cells of the eye to
migrate and reproduce, and thereby protect against PCO. It is
expected that the amount of drug required for this therapy will be
in the picogram to microgram range. The therapeutic drugs loaded
into the intraocular lens can include cytostatic agents (i.e.,
antiproliferation agents that prevent or delay cell division, for
example, by inhibiting replication of DNA or by inhibiting spindle
fiber formation, and/or inhibit the migration of cells into the
posterior space).
[0072] Representative examples of cytostatic agents include the
following: [0073] modified toxins; [0074] methotrexate; [0075]
adriamycin [0076] radionuclides (e.g., such as disclosed in U.S.
Pat. No. 4,897,255, herein incorporated by reference in it
entirety); [0077] protein kinase inhibitors, including staurosporin
(which is a protein kinase C inhibitor) as well as a
diindoloalkaloids and stimulators of the production or activation
of TGF-beta, including tamoxifen and derivatives of functional
equivalents (e.g., plasmin, heparin, compounds capable of reducing
the level or inactivating the lipoprotein Lp(a) or the glycoprotein
apolipoprotein(a) thereof) [0078] nitric oxide releasing compounds
(e.g., nitroglycerin) or analogs or functional equivalents thereof;
[0079] paclitaxel or analogs or functional equivalents thereof
(e.g., taxotere), for example an agent based on Taxol.RTM. (whose
active ingredient is paclitaxel); [0080] inhibitors of specific
enzymes (such as the nuclear enzyme DNA topoisomerase II and DAN
polymerase, RNA polyermase, adenl guanyl cyclase); [0081]
superoxide dismutase inhibitors; [0082] terminal
deoxynucleotidyl-transferas; [0083] reverse transcriptase; [0084]
antisense oligonucleotides that suppress smooth muscle cell
proliferation; [0085] angiogenesis inhibitors (e.g., endostatin,
angiostatin and squalamine); [0086] rapamycin; [0087] cerivastatin;
and [0088] flavopiridol and suramin and the like.
[0089] Other examples of cytostatic agents include the following:
[0090] peptidic or mimetic inhibitors (i.e., antagonists, agonists,
or competitive or non-competitive inhibitors) of cellular factors
that may (e.g., ion the presence of extracellular matrix) trigger
proliferation of cells or pericytes (e.g., cytokines (for example,
interleukins such as IL-1), growth factors (for example, PDGF,
TGF-alpha or -beta, tumor necrosis factor, smooth muscle- and
endothelial-derived growth factors such as endothelin or FGF),
homing receptors (for example, for platelets or leukocytes), and
extracellular matrix receptors (for example, integrins).
[0091] Representative examples of useful therapeutic agents in the
category of agents that address cell proliferation include: [0092]
subfragments of heparin; [0093] triazolopyrimidine (for example,
trapidil, which is a PDGF antagonist); [0094] lovastatin; and
[0095] prostaglandins E1 or I2.
[0096] Representative examples of therapeutic agents that inhibit
migration of cells into the posterior space include the following:
[0097] agents derived from phenylalanine (for example
cytochalasins), tryptophan (for example (chetogobosins), or leucine
(for example, asphalasins, resulting in a benzyl, indol-3-yl methyl
or isobutyl group, respectively, at position C-3 of a substituted
perhydroisoindole-1-one moiety.
[0098] Several of the above and numerous additional therapeutic
agents appropriate for the practice of the present invention are
disclosed in U.S. Pat. Nos. 5,733,925 and 6,545,097, both of which
are herein incorporated by reference in their entirety.
[0099] If desired, a therapeutic agent of interest can be provided
at the same time as the copolymer, for example, by adding it to a
copolymer melt during thermoplastic processing or by adding it to a
copolymer solution during solvent-based processing. The therapeutic
agent can be added to the optics portion or to the haptic elements
or to both the optics portion and the haptic elements of the lens
device.
[0100] Alternatively, a therapeutic agent can be provided after
formation of the device or device portion. As an example of these
embodiments, the therapeutic agent can be dissolved in a solvent
that is compatible with both the copolymer and the therapeutic
agent. Preferably, the lens copolymer is at most only slightly
soluble in the solvent. Subsequently, the solution is contacted
with the device or device portion such that the therapeutic agent
is loaded (e.g., by leaching/diffusion) into the copolymer. For
this purpose, the device or device portion can be immersed or
dipped into the solution, the solution can be applied to the device
or component, for example, by spraying, printing dip coating,
immersing in a fluidized bed and so forth. The device or component
can subsequently be dried, with the therapeutic agent remaining
therein.
[0101] In another alternative, the therapeutic agent may be
provided within a matrix comprising the copolymer of the
intraocular lens. The therapeutic agent can also be covalently
bonded, hydrogen bonded, or electrostatically bound to the
copolymer. As specific examples, nitric oxide releasing functional
groups such as S-nitroso-thiols can be provided in connection with
the copolymer, or the copolymer can be provided with charged
functional groups to attach therapeutic groups with oppositely
charged functionalities.
[0102] In yet another alternative embodiment, the therapeutic agent
can be precipitated onto the surface of a lens device or lens
device portion. This surface can be subsequently covered with a
coating of copolymer (with or without additional therapeutic agent)
as described above.
[0103] Hence, when it is stated herein that the copolymer is
"loaded" with therapeutic agent, it is meant that the therapeutic
agent is associated with the copolymer in a fashion like those
discussed above or in a related fashion.
[0104] In some instances a binder may be useful for adhesion to a
substrate. Examples of materials appropriate for binders in
connection with the present invention include silanes, titanates,
isocyanates, carboxyls, amides, amines, acrylates hydroxyls, and
epoxides, including specific polymers such as EVA, polyisobutylene,
natural rubbers, polyurethanes, siloxane coupling agents, ethylene
and propylene oxides.
[0105] It also may be useful to coat the copolymer of the lens
(which may or may not contain a therapeutic agent) with a layer
with an additional polymer layer (which may or may not contain a
therapeutic agent). This layer may serve, for example, as a
boundary layer to retard diffusion of the therapeutic agent and
prevent a burst phenomenon whereby much of the agent is released
immediately upon exposure of the lens device or device portion to
the implant site. The material constituting the coating, or
boundary layer, may or may not be the same copolymer as the loaded
copolymer.
[0106] For example, the barrier layer may also be a polymer or
small molecule from the following classes: polycarboxylic acids,
including polyacrylic acid; cellulosic polymers, including
cellulose acetate and cellulose nitrate; gelatin;
polyvinylpyrrolidone; cross-linked polyvinylpyrrolidone;
polyanhydrides including maleic anhydride polymers; polyamides;
polyvinyl alcohols; copolymers of vinyl monomers such as EVA
(ethylene-vinyl acetate copolymer); polyvinyl ethers; polyvinyl
aromatics; polyethylene oxides; glycosaminoglycans;
polysaccharides; polyesters including polyethylene terephthalate;
polyacrylamides; polyethers; polyether sulfone; polycarbonate;
polyalkylenes including polypropylene, polyethylene and high
molecular weight polyethylene; halogenated polyalkylenes including
polytetrafluoroethylene; polyurethanes; polyorthoesters;
polypeptides, including proteins; silicones; siloxane polymers;
polylactic acid; polyglycolic acid; polycaprolactone;
polyhydroxybutyrate valerate and blends and copolymers thereof;
coatings from polymer dispersions such as polyurethane dispersions
(BAYHDROL.RTM., etc.); fibrin; collagen and derivatives thereof;
polysaccharides such as celluloses, starches, dextrans, alginates
and derivatives; and hyaluronic acid. Copolymers and mixtures of
the above are also contemplated.
[0107] It is also possible to form the lens device (or lens device
portion) with blends by adding one or more of the above or other
polymers to a block copolymer. Examples include the following:
[0108] blends can be formed with homopolymers that are miscible
with one of the block copolymer phases. For example, polyphenylene
oxide is miscible with the styrene blocks of
polystyrene-polyisobutylene-polystyrene copolymer. This should
increase the strength of a molded part or coating made from
polystyrene-polyisobutylene-polystyrene copolymer and polyphenylene
oxide. [0109] blends can be made with added polymers or other
copolymers that are not completely miscible with the blocks of the
block copolymer. The added polymer or copolymer may be
advantageous, for example, in that it is compatible with another
therapeutic agent, or it may alter the release rate of the
therapeutic agent from the block copolymer (e.g.,
polystyrene-polyisobutylene-polystyrene copolymer). [0110] blends
can be made with a component such as sugar (see list above) that
can be leached from the device or device portion, rendering the
device or device component more porous and controlling the release
rate through the porous structure.
[0111] The release rate of therapeutic agent from the
therapeutic-agent-loaded block copolymers of the present invention
can be varied in a number of ways. Examples include: [0112] varying
the molecular weight of the block copolymers; [0113] varying the
specific constituents selected for the elastomeric and
thermoplastic portions of the block copolymers and the relative
amounts of these constituents; [0114] varying the type and relative
amounts of solvents used in processing the block copolymers; [0115]
varying the porosity of the block copolymers; [0116] providing a
boundary layer over the block copolymer; and [0117] blending the
block copolymer with other polymers or copolymers.
[0118] Moreover, although it is seemingly desirable to provide
control over the release of the therapeutic agent (e.g., as a fast
release (hours) or as a slow release (weeks)), it may not be
necessary to control the release of the therapeutic agent. In such
embodiments, one or more of the therapeutic drug agents described
herein (e.g., an antiproliferative agent derived from paclitaxyl)
may be injected into the lens capsule at the time of surgery. In
this case, the agent "sterilizes" the tissue cells that cause PCO
within the short time it exists in the eye, and it can be delivered
neat (without a carrier) at the time of surgery.
[0119] For ocular applications, it is desirable that the material
of at least the optic of the ocular lens device maintain in vivo
transparency for substantial periods of time. As used herein, "in
vivo transparency" or "transparent" shall mean that the material
transmits at least 80% of the light incident thereon in the visible
range (e.g., between 400 and 700 nm of the electromagnetic
spectrum). It was found that a film of SIBS material formed by
traditional thermal processing techniques (e.g., injection molding,
compression molding, or extrusion at temperatures at or near the
melting point of the SIBS material and then slow cooled to cure the
polymer) is transparent in air; however, the film begins to cloud
and become opaque with time when equilibrated in water, saline or
other aqueous bodily fluids (collectively referred to below as
"water"). Further, the extent of such clouding increases as the
water is heated. At temperatures near the boiling point of water,
the SIBS film becomes totally white-opaque and can absorb as much
as 10% of its weight in water. Considering that the SIBS material
is comprised of polyisobutylene and polystyrene, which are both
hydrophobic material, this result is surprising.
[0120] In accord with the present invention, the
polyisobutylene-based material of at least the optic of the ocular
lens devices described herein is adapted to maintain in vivo
transparency for substantial periods of time. Generally, this is
accomplished by satisfying the following two steps: 1) washing
remnant salts and other unwanted chemicals from the
polyisobutylene-based material; and 2) processing the washed
polyisobutylene-based material at a controlled temperature(s)
and/or a controlled processing time(s) to form the optic and
possibly other parts of the ocular lens devices described herein.
In one methodology, the optic (and possibly other parts of the
ocular lens device) is formed by processing the
polyisobutylene-based polymer material at controlled temperatures
that are significantly less that the melting point of the
polyisobutylene-based polymer. In another methodology, the optic
(and possibly other parts of the ocular lens device) is formed by
rapidly heating the polyisobutylene-based polymer to a temperature
at or near its melting point. The resultant polymer melt is added
to a mold that forms the optic (and possibly other parts of the
ocular lens device). The polymer and mold is quickly cooled back to
room temperature for removal of the optic. In addition, optical
clarity additives may be added to the polyisobutylene-based
material to help in this regard; however, it is not always desirous
to use these additives as they may leach from the polymer and into
the ocular environment and provoke an undesirable response.
[0121] The polyisobutylene-based material is typically synthesized
in organic solvent using a Lewis acid as an initiator. One such
Lewis acid that is preferred for this application is titanium
tetrachloride. In order to quench the reaction, chemicals such as
alcohols (methanol, for example) are added in excess to the
reaction stoichiometry which immediately quenches the reaction by
neutralizing titanium tetrachloride. At completion of the reaction,
titanium tetrachloride is converted into various salts of titanium,
including titanium dioxide, titanium methoxide, and the like. In
addition, depending upon the reaction vessel used, various salts of
titanium can form with materials inherent to the reaction vessel,
especially if the vessel is comprised of stainless steel--these
salts render the material black with time. Nevertheless, a
consequence of adding these reactant materials is that in order to
render the material clean and highly transparent, these excess
materials and their byproducts must be removed from the polymer
upon completion of the reaction.
[0122] These remnant salts and other unwanted chemicals are
preferably washed from the polyisobutylene-based material by
washing the polymer in a separatory funnel with salt water, with
pure water and with repeated precipitations in excess polar solvent
(such as isopropanol, acetone, methanol, ethanol and the like).
Other well-known washing procedures can also be used. Note that if
the material is not washed of salts, these hygroscopic salts begin
to draw in water when the material is equilibrated in water. Voids
where the salts have been trapped are readily viewed under scanning
electron microscopy and these voids become filled with water as the
salt is dissolved out. As water has a refractive index of
approximately 1.33 and material has a refractive index of 1.53, the
difference in refractive index is sufficient to render the polymer
cloudy and at times totally opaque. If the material is washed
appropriately, these salts are removed and voids no longer
exist.
[0123] In one methodology, the polyisobutylene-based material of
the optic (and possibly other parts of the ocular device described
herein) is formed and molded at temperatures that are significantly
less the melting point of the material by casting the material from
a solution. This is accomplished by dissolving the
polyisobutylene-based material in a solvent (such as hexanes,
toluene, methylcyclohexane, cyclopentane, and the like) and casting
the resulting solution. Because casting from solution affords
control over only one side of the lens, it is difficult to
accurately form a lens with opposing optical surfaces utilizing
casting from solution alone. In these applications, casting from
solution is preferably used to form a lens preform that is finished
by compression molding.
[0124] More particularly, the solution comprising the dissolved
polyisobutylene-based material is cast into a preform mold thereby
forming one or more lens preforms. The shape and dimensions of the
preform mold approach the geometry of the desired end product lens.
The lens preform(s) is (are) removed from preform mold and placed
into a compression mold. The compression mold is pressed closed and
heated for a predetermined duration at temperatures that are
significantly less than the melting point of the material. The
heating temperature and duration are selected such that the lens
preform flows to its desired final shape (with optically finished
surfaces and the desired curvature) while the material maintains
it's casting morphology. The end product lens is then removed from
the compression mold. Once cooled, it has been found that the end
product lens will maintain high transparency in the ocular
environment.
[0125] The SIBS material has a melting point between 200.degree. C.
and 250.degree. C. In this case, the heating temperature utilized
during the compression molding operations is preferably in the
range between 100.degree. C. and 120.degree. C. for a duration
between 10 to 90 minutes. At these parameters, the SIBS material
maintains its casting morphology, that is the domain segments
remain intact and simply flow to fill the mold cavity.
[0126] The casting by solution operations that construct the
preform preferably utilize a centrifugal casting technique wherein
a sheet of the polyisobutylene-based material is cast within a
rotating cylinder as shown in FIG. 10. The inside of the cylinder
1001 is lined with a Teflon.RTM. skin 1003. An array of evenly
spaced indentations 1005 are milled into the inner surface of the
Teflon.RTM. skin (but not through the skin) preferably using a ball
mill. The rotating cylinder 1001 is supported in an oven (not
shown) that is operated at a heating temperature preferably in the
range between 40.degree. C. and 60.degree. C. The cylinder is
rotated about is central axis preferably at a rotation speed of
approximately 3000 RPM. As the cylinder 1001 is rotated, the
polyisobutylene-based solution (for example, polyisobutylene-based
material dissolved in toluene solvent at a 10% wt/wt ratio) is
injected into the cylinder 1001 as pictorially represented by the
arrows 1007. The rotation of the cylinder 1001 produces centrifugal
forces that force the solution against the inner surface of the
skin 1003 and into the indentations 1005. The process can be
repeated until the desired film thickness is obtained. The film is
then dried (typically requiring several hours drying time) and
removed from the cylinder. The film consists of a ribbon of preform
lenses (bumps) that are evenly located along the ribbon. These
preform lenses approach the geometry of the desired end product
lens, except that the surfaces are not optically finished nor set
to the desired curvature. The lens preforms are cut out (trephined)
from the ribbon and placed into a compression mold that forms the
end product lens. Note that other polymeric casting techniques,
such as spin casting techniques, can also be used to construct the
lens preforms at low temperatures relative to the melting point of
the polyisobutylene-based material.
[0127] The centrifugal casting of preform lenses together with
compression molding finishing of the lenses advantageously provide
a flexible, biocompatible polyisobutylene-based lens that maintains
high transparency in ocular fluid over time. Such operations are
also advantageous because they avoid the inefficiencies of the
prior art manufacturing methods. More specifically, the use of the
Teflon.RTM. skin on the inner surface of the centrifugal caster
reduces the amount of cleaning that is required between mold
cycles. In addition, the low temperature compression molding
operations helps reduce flash formation. These features provide for
improved production cost efficiencies over the prior art
manufacturing methods.
[0128] In another methodology, the optic (and possibly other parts
of the ocular lens device) is formed by rapidly heating the
polyisobutylene-based polymer to a temperature at or near its
melting point. The resultant polymer melt is added to a mold that
forms the optic (and possibly other parts of the ocular lens
device). The polymer and mold is quickly cooled back to room
temperature for removal from the mold. The polymer may be heated in
the mold, or heated outside the mold and added to the mold in its
melt state. For a polymer with 10 mole percent styrene content, the
heating temperature range is 150.degree. C. to 200.degree. C. and
more preferably between 170.degree. C. to 180.degree. C.
Preferably, the polyisobutylene-based polymer is rapidly heated in
a mold to this temperature and the mold closed and pressurized to
greater than 500 psi and then immediately rapidly cooled to room
temperature. The rapid cooling can be accomplished by cooling
coils, liquid nitrogen or the like. The entire rapid
heating-cooling cycle is preferably less than three (3) minutes,
and more preferably less than one (1) minute such that the optic
maintains in vivo transparency.
[0129] One can speculate that forming the ocular lens by
traditional thermal processing of the polyisobutylene-based
material without rapid heating and cooling results in clouding in
water due to the entrapment of water molecules amongst the
polyisobutylene chain segments. More particularly, when such
material is heated to a temperature at or near its melting
temperature and then allowed to slowly cool to room temperature,
the glassy segments aggregate and segregate themselves from the
soft polyisobutylene segments. This phase segmentation is known to
occur in these types of polymers as well as in other polymers, such
as polyurethane, and the like. It is further theorized that the
water molecules are trapped in the segments as when pure
polyisobutylene is immersed in water it clouds, whereas polystyrene
does not cloud. Further, when the polymer is heated, there is more
motility or vibration in the chains, further entrapping water and
hastening the clouding as well as the extent of clouding. However,
the polyisobutylene-based material cast from solution seems to
segregate differently and experiences minimal clouding in
water.
Example 1
[0130] An ocular lens is constructed from a polyisobutylene-based
material cast from solution with a thickness of less than
approximately 0.03 inches. The lens is placed in a water bath at
36.degree. C. and maintains 95%-100% transparency in the visible
spectrum over a period of two months.
Example 2
[0131] An ocular lens is constructed from a polyisobutylene-based
material cast from solution with a thickness of approximately 0.04
inches. The lens is placed in a water bath at 36.degree. C. and a
slight amount of clouding is observed by the naked eye after two
days. Thereafter, lens maintains a transparency of 85%-95% in the
visible spectrum over a period of two months.
Example 3
[0132] An ocular lens is molded from polyisobutylene-based material
in conjunction with rapid heating and cooling of the material with
a thickness of less than approximately 0.03 inches. The lens is
placed in a water bath at 36.degree. C. and a slight amount of
clouding is observed by the naked eye after two days. Thereafter,
lens maintains a transparency of 85%-95% in the visible spectrum
over a period of two months.
[0133] Optical clarity additives, such as mineral oil, paraffinic
oil, naphthalic oil and small chains of polyisobutylene, and the
like, can be added to the polyisobutylene to help fill the voids
between the polyisobutylene strands that would otherwise trap
water. Preferably, such additives are added to the polyisobutylene
polymer at a ratio between 1% to 3% wt/wt. These optical clarity
additives also help maintain the lenses highly transparent in both
air and water; however, these additives are generally not desirable
for implantation applications as they may leach from the
polyisobutylene polymer into the ocular environment and provoke an
undesirable response.
[0134] As noted above, the polyisobutylene-based material used in
connection with the present invention is endowed with good
biocompatibility. The biocompatibility of a
polystyrene-polyisobutylene-polystyrene SIBS copolymer for the
illustrative intraocular lens described herein is demonstrated
below in connection with the following non-limiting example.
Example 4
[0135] Materials and Methods: SIBS material having a triblock
polymer backbone comprising polystyrene-polyisobutylene-polystyrene
of mole percent styrene content 9.8%, 21.5% and 23.4%,
respectively, were synthesized by living end carbocationic
polymerization techniques. Also synthesized was a control material
made from medical grade polydimethylsiloxane (PDMS, RI=1.41). Both
the SIBS material and the PDMS material were compression molded at
160.degree. C. into flat disks, 3 mm and 6 mm diameter, all being
300 .mu.m thick. The disks were implanted in four groups of two New
Zealand White rabbits using conventional surgical techniques.
Maxitrol topical ointment was given for three days. No medications
were given thereafter. Full ophthalmic examinations were performed
weekly using a slit-lamp biomicroscope. Two animals with an
endocapsular implant (intraocular lens) were followed until the
eighth week and six animals with intracorneal and subtenon implants
were followed until the twelfth week before euthanasia for
histology.
[0136] Results: No inflammation, infection, toxic reaction and
implant migration were observed. The cornea, sclera, iris, ciliary
body, choroids, vitreous and retina remained normal in all animals.
No neovascularization or fibrosis could be detected around any SIBS
disks implanted intracorneally. Subtenon PDMS control implants
elicited a moderate neovascularization reaction whereas the SIBS
samples did not. Encapsulation was approximately 200 .mu.m for PDMS
and was well organized and consistent around the sample. In
addition, gross histology showed neovascularization (an ingrowth of
capillaries) radiating from the sample. The histology for the SIBS
samples routinely demonstrated a loose unorganized fibrous network
with variable thickness ranging from 0 to 100 .mu.m around the
sample with no signs of neovascularization. Scanning Electron
Microscopy of the explanted SIBS discs showed no signs of
biodegradation.
[0137] Conclusion: SIBS material is intraorbitally and
intraocularly biocompatible and does not encapsulate in the eye,
and thus is suitable for use in intraocular implant devices.
[0138] There have been described and illustrated herein several
embodiments of intraocular lens and surgical methods associated
therewith. While particular embodiments of the invention have been
described, it is not intended that the invention be limited
thereto, as it is intended that the invention be as broad in scope
as the art will allow and that the specification be read likewise.
For example, it will be recognized that adaptations may be made of
the lens structures described herein. More particularly, in the
event that optic portion of the lens employs one or more square
edges, such edges introduce facets that can cause glare from
peripheral light sources. Such glare can be eliminated by frosting
the edge of the optic. Alternatively, the shape and configuration
of the optic of the lens may be varied. For example, the optic may
be realized by first and second lens elements that are designed to
be held in place along the optical axis of the eye. The first lens
element, which is located posteriorly relative to the second lens,
preferably has a negative power while the second lens element has a
positive power. A polymeric gel (for example, one formed of the in
vivo SIBS material described herein) may be disposed between the
two lens elements. One or more of the therapeutic drug agents
described herein (e.g., an antiproliferative agent derived from
paclitaxyl) may be added to the polymeric gel to inhibit PCO. In
yet other embodiments, one or more of the therapeutic drug agents
described herein (e.g., an antiproliferative agent derived from
paclitaxyl) may be associated with an ancillary device implanted in
vivo in the eye, such as a lens tensioning device, a small patch
reservoir, or as a microcapsule. In another example, the lens
devices described herein can be placed in the anterior chamber, in
the posterior chamber, or in the vitreous chamber. In yet another
example, the lens described herein can be used in conjunction with
the natural crystalline lens (e.g., the natural crystalline lens is
not removed) for eyes that suffer from severe refractive errors, or
can also be used as a lens for corneal replacement, or for contact
lens devices.
[0139] Moreover, while particular methods of manufacture have been
disclosed, it will be understood that other manufacturing methods
can be used. For example, because the copolymer materials described
herein have a thermoplastic character, a variety of standard
thermoplastic processing techniques can be used to for the devices
described herein. Such techniques include compression molding,
injection molding, blow molding, spinning, vacuum forming and
calendaring, and extrusion into tubes and the like. Such devices
can also be made using solvent-based techniques involving solvent
casting, spin coating, solvent spraying, dipping, fiber forming,
ink jet techniques and the like.
[0140] It is also contemplated that the optically transparent
polyisobutylene-based material described herein (and methods of
fabricating such material) can be utilized into other medical
implant applications.
[0141] It will therefore be appreciated by those skilled in the art
that yet other modifications could be made to the provided
invention without deviating from its spirit and scope as
claimed.
* * * * *