U.S. patent application number 17/490963 was filed with the patent office on 2022-01-20 for method of adjusting a blended extended depth of focus light adjustable lens with laterally offset axes.
The applicant listed for this patent is RxSight, Inc.. Invention is credited to Pablo Artal, Ilya Goldshleger, Matt Haller, John Kondis, Christian A. Sandstedt, Eloy Angel Villegas.
Application Number | 20220015893 17/490963 |
Document ID | / |
Family ID | 1000005872299 |
Filed Date | 2022-01-20 |
United States Patent
Application |
20220015893 |
Kind Code |
A1 |
Goldshleger; Ilya ; et
al. |
January 20, 2022 |
METHOD OF ADJUSTING A BLENDED EXTENDED DEPTH OF FOCUS LIGHT
ADJUSTABLE LENS WITH LATERALLY OFFSET AXES
Abstract
A Light Adjustable Lens (LAL) comprises a central region,
centered on a central axis, having a position-dependent central
optical power, and a peripheral annulus, centered on an annulus
axis and surrounding the central region, having a
position-dependent peripheral optical power; wherein the central
optical power is at least 0.5 diopters different from an average of
the peripheral optical power, and the central axis is laterally
shifted relative to the annulus axis. A method of adjusting the LAL
comprises implanting a LAL; applying a first illumination to the
LAL with a first illumination pattern to induce a
position-dependent peripheral optical power in at least a
peripheral annulus, centered on an annulus axis; determining a
central region and a corresponding central axis of the LAL; and
applying a second illumination to the LAL with a second
illumination pattern to induce a position-dependent central optical
power in the central region of the LAL.
Inventors: |
Goldshleger; Ilya; (Ladera
Ranch, CA) ; Kondis; John; (Irvine, CA) ;
Haller; Matt; (Costa Mesa, CA) ; Sandstedt; Christian
A.; (Pasadena, CA) ; Artal; Pablo; (Molinda De
Segura, ES) ; Villegas; Eloy Angel; (Alicante,
ES) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RxSight, Inc. |
Aliso Viejo |
CA |
US |
|
|
Family ID: |
1000005872299 |
Appl. No.: |
17/490963 |
Filed: |
September 30, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16236659 |
Dec 31, 2018 |
11135052 |
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17490963 |
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13488099 |
Jun 4, 2012 |
10874505 |
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16236659 |
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61535793 |
Sep 16, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2/1624 20130101;
A61F 2/164 20150401; A61L 27/18 20130101; A61F 2002/1683
20130101 |
International
Class: |
A61F 2/16 20060101
A61F002/16; A61L 27/18 20060101 A61L027/18 |
Claims
1. A method of adjusting a Light Adjustable Lens (LAL), the method
comprising the steps of: implanting a LAL into an eye; applying a
first illumination to the LAL with a first illumination pattern to
induce a position-dependent peripheral optical power in at least a
peripheral annulus, centered on an annulus axis; determining a
central region and a corresponding central axis of the LAL; and
applying a second illumination to the LAL with a second
illumination pattern to induce a position-dependent central optical
power in the central region of the LAL; wherein the central axis is
laterally shifted relative to the annulus axis, and an average of
the central optical power is at least 0.5 diopters different from
an average of the peripheral optical power.
2. The method of claim 1, wherein: the average of the central
optical power is at least 1.0 diopter different from the average of
the peripheral optical power.
3. The method of claim 1, wherein: the average of the central
optical power is at least 0.5 diopters higher than an average of
the peripheral optical power.
4. The method of claim 1, wherein: the average of the central
optical power is at least 0.5 diopters lower than an average of the
peripheral optical power.
5. The method of claim 1, the applying the first illumination
comprising: applying the first illumination with a first
illumination pattern to induce the position-dependent peripheral
optical power in a light-adjusted region that includes the
peripheral annulus and the central region.
6. The method of claim 1, the determining a central axis
comprising: identifying a visual axis of the eye as the central
axis.
7. The method of claim 1, the determining a central axis
comprising: determining the central axis with an iris of the eye
being in a non-dilated state.
8. The method of claim 1, the determining a central axis
comprising: determining the central axis with an iris of the eye
being dilated to an iris-radius no more than 30% greater than a
non-dilated iris-radius.
9. The method of claim 1, the determining a central axis
comprising: determining the central axis before an iris of the eye
is dilated; registering the determined central axis with a feature
of the eye; and reconstructing the determined and registered
central axis after the iris is dilated, before the applying of the
second illumination.
10. The method of claim 1, wherein: the applying the first
illumination and the applying the second illumination induces a
transition between the central region and the peripheral annulus,
having a transition optical power that changes from the central
optical power to the peripheral optical power.
11. The method of claim 1, wherein: the central optical power has
an approximately flat position-dependence, having an optical power
variation less than 0.2 diopters over a central 50% of the central
region.
12. The method of claim 1, wherein: a spherical aberration caused
by the position-dependence of one of the peripheral optical power,
and a combination of the central optical power, the peripheral
optical power, and a transition optical power, is in a range of
-0.05 .mu.m to -1 .mu.m at a diameter of 4 mm in a plane of the
LAL.
13. The method of claim 1, wherein: a spherical aberration caused
by the position-dependence of one of the peripheral optical power,
and a combination of the central optical power, the peripheral
optical power, and a transition optical power, is in a range of
-0.05 .mu.m to -2 .mu.m at a diameter of 6 mm in a corneal plane of
an eye upon an implantation of the LAL in the eye.
14. The method of claim 1, wherein: at least on the central optical
power and the peripheral optical power is selected such that a
spherical aberration caused by the position-dependence of at least
one of the central optical power and the peripheral optical power
approximately compensates a spherical aberration of a cornea of the
eye.
15. The method of claim 1, wherein: at least one of the
position-dependent central optical power involves a cylinder
angular dependence; and the position-dependent peripheral optical
power involves a cylinder angular dependence.
16. The method of claim 1, wherein: the applying the first
illumination and the applying the second illumination is separated
by less than 48 hours.
17. The method of claim 1, comprising: applying a lock-in
illumination, to lock in the induced peripheral optical power and
the induced central optical power in the LAL.
18. The method of claim 1, further comprising: applying a third
illumination to the LAL with a third illumination pattern centered
on the central axis to reduce the position-dependent central
optical power, induced in by the second illumination in the central
region of the LAL.
19. A method of adjusting a Light Adjustable Lens (LAL), the method
comprising the steps of: implanting a LAL into an eye, the LAL
having a pre-molded position-dependent peripheral optical power in
at least a peripheral annulus, centered on an annulus axis;
determining a central region and a corresponding central axis of
the LAL; and applying a central illumination to the LAL with a
central illumination pattern to induce a position-dependent central
optical power in the central region of the LAL; wherein the central
axis is laterally shifted relative to the annulus axis, and an
average of the central optical power is at least 0.5 diopters
different from an average of the peripheral optical power.
20. A method of adjusting a Light Adjustable Lens (LAL), the method
comprising the steps of: implanting a LAL, having a LAL axis, into
an eye; and applying an illumination to the LAL with an
illumination pattern to induce a position-dependent optical power
in a light-adjusted region, centered on an adjustment axis; wherein
the adjustment axis is laterally shifted relative to the LAL axis.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a Continuation of U.S.
application Ser. No. 16/236,659, filed Dec. 31, 2018, which is a
Continuation-In-Part of U.S. application Ser. No. 13/488,099, filed
on Jun. 4, 2012, now Issued as U.S. Pat. No. 10,874,505, issued on
Dec. 29, 2020, which claims the benefit of Provisional Application
No. 61/535,793, filed on Sep. 16, 2011, entitled "Using the Light
Adjustable Lens (Lal) To Increase the Depth of Focus by Inducing
Targeted Amounts of Asphericity," the contents of each are
incorporated herein by reference in their entirety for all
purposes.
TECHNICAL FIELD
[0002] The field of the invention includes at least medical and
surgical instruments; treatment devices; surgery and surgical
supplies; and, medicine. In general, the field of subject matter of
the invention includes ophthalmology. More specifically, the
disclosure relates to optical elements, which can be modified
post-manufacture such that different versions of the element will
have different optical properties. In particular, the disclosure
relates to lenses, such as intraocular lenses, which can be
converted into aspheric lenses post-fabrication. This invention
relates to light adjustable lenses with a depth of focus, and more
specifically to blended extended depth of focus light adjustable
lenses and to the methods of adjusting these lenses by
illumination.
BACKGROUND
[0003] An intraocular lens (IOL) is a surgically implanted,
polymeric lens designed to replace the natural crystalline lens in
the human eye, typically in patients who have developed visually
significant cataracts. Since their inception in the late 1940's,
IOLs have provided improved uncorrected visual acuity (UCVA)
compared to that of the cataractous or aphakic state; however,
problems in predictably achieving emmetropia persist as most
post-cataract surgery patients rely on spectacles or contact lenses
for optimal distance vision. Compounding the issues related to
achieving optimum distance vision, patients undergoing cataract
surgery lose their ability to accommodate, i.e. the ability to see
objects at both near and distance.
[0004] The determination of IOL power required for a particular
post-operative refraction is dependent on the axial length of the
eye, the optical power of the cornea, and the predicted location of
the IOL within the eye. Accurate calculation of IOL power is
difficult because the determination of axial length, corneal
curvature, and the predicted position of the IOL in the eye is
inherently inaccurate. (Narvaez et al., 2006; Olsen, 1992;
Preussner et al., 2004; Murphy et al., 2002). Surgically induced
cylinder and variable lens position following implantation will
create refractive errors, even if preoperative measurements were
completely accurate. (Olsen, 1992) Currently, the options for IOL
patients with less than optimal uncorrected vision consist of
post-operative correction with spectacles, contact lenses or
refractive surgical procedures. Because IOL exchange procedures
carry significant risk, secondary surgery to remove the IOL and
replace the first IOL with a different power IOL is generally
limited to severe post-operative refractive errors.
[0005] With current methods of IOL power determination, the vast
majority of patients achieve a UCVA of 20/40 or better. A much
smaller percentage achieves optimal vision without spectacle
correction. Nearly all patients are within two diopters (D) of
emmetropia.
[0006] In a study of 1,676 patients, 1,569 (93.6%) patients were
within two diopters of the intended refractive outcome. (Murphy et
al., 2002). In 1,320 cataract extractions on patients without
ocular co-morbidity, Murphy and co-workers found that 858 (65%) had
uncorrected visual acuity greater than 20/40. (Murphy et al.,
2002). A 2007 survey of cataract surgeons reported that incorrect
IOL power remains a primary indication for foldable IOL
explantation or exchange. (Mamalis et al., 2008; and Jin et al.,
2007)
[0007] In addition to imprecise IOL power determinations,
post-operative uncorrected visual acuity is most often limited by
pre-existing astigmatism. Staar Surgical (Monrovia, Calif.) and
Alcon Laboratories (Ft. Worth, Tex.) both market a toric IOL that
corrects pre-existing astigmatic errors. These IOLs are available
in only two to three toric powers (2.0, 3.5 D and 1.50, 2.25 and
3.0 D, respectively at the IOL plane) and the axis must be
precisely aligned at surgery. Other than surgical repositioning,
there is no option to adjust the IOL's axis which may shift
post-operatively. (Sun et al., 2000) Furthermore; individualized
correction of astigmatism is limited by the unavailability of
multiple toric powers.
[0008] An additional problem associated with using pre-implantation
corneal astigmatic errors to gauge the required axis and power of a
toric IOL is the unpredictable effect of surgical wound healing on
the final refractive error. After the refractive effect of the
cataract wound stabilizes, there is often a shift in both magnitude
and axis of astigmatism which off-sets the corrective effect of a
toric IOL. Therefore, a means to post-operatively adjust (correct)
astigmatic refractive errors after lens implantation and surgical
wound healing is very desirable. While limbal relaxing incision is
a widely accepted technique for treating corneal astigmatism, the
procedure is typically performed during cataract surgery;
therefore, the procedure does not address the effect of
post-implantation wound healing.
[0009] In the United States alone, approximately one million eyes
undergo corneal refractive procedures which subsequently develop
cataracts, thus, presenting a challenge with respect to IOL power
determination. Corneal topographic alterations induced by
refractive surgery reduce the accuracy of keratometric
measurements, often leading to significant post-operative
ametropia. (Feiz et al., 2005; Wang et al., 2004; Latkany et al.,
2005; Mackool et al., 2006; Packer et al., 2004; Fam and Lim, 2008;
Chokshi et al., 2007; Camellin and Calossi, 2006). Recent studies
of patients who have had corneal refractive surgery
(photorefractive keratectomy, laser in situ keratomileusis, radial
keratotomy) and subsequently required cataract surgery frequently
demonstrate refractive "surprises" post-operatively. As the
refractive surgery population ages and develops cataracts,
appropriate selection of IOL power for these patients has become an
increasingly challenging clinical problem. The ability to address
this problem with an adjustable IOL is valuable to patients seeking
optimal distance vision after cataract surgery.
[0010] Accommodation, as it relates to the human visual system,
refers to the ability of a person to use their unassisted ocular
structure to view objects at both near (e.g. reading) and far (e.g.
driving) distances. The mechanism whereby humans accommodate is by
contraction and relaxation of the ciliary body, which connects onto
the capsular bag surrounding the natural lens. Under the
application of ciliary stress, the human lens will undergo a shape
change effectively altering the radius of curvature of the lens.
(Ciuffreda, 1998). This action produces a concomitant change in the
power of the lens. However, as people grow older the ability for
their eyes to accommodate reduces dramatically. This condition is
known as presbyopia and currently affects more than 90 million
people in the United States. The most widely accepted theory to
explain the loss of accommodation was put forth by Helmholtz.
According to Helmholtz, as the patient ages, the crystalline lens
of the human eye becomes progressively stiffer prohibiting
deformation under the applied action of the ciliary body.
(Helmholtz, 1969). People who can see objects at a distance without
the need for spectacle correction, but have lost the ability to see
objects up close are usually prescribed a pair of reading glasses
or magnifiers. For those patients who have required previous
spectacle correction due to preexisting defocus and/or astigmatism,
they are prescribed a pair of bifocals, trifocals, variable, or
progressive focus lenses which allows the person to have both near
and distance vision. Compounding this condition is the risk of
cataract development as the patient ages.
[0011] To effectively treat both presbyopia and cataracts, the
patient can be implanted with a multifocal IOL. The two most widely
adopted multifocal IOLs currently sold in the United States are the
ReZoom.RTM. (Abbott Medical Optics, Santa Ana, Calif.) and
ReStor.RTM. (Alcon, Fort Worth, Tex.) lenses. The ReZoom.RTM. lens
is comprised of five concentric, aspheric refractive zones. (U.S.
Pat. No. 5,225,858). Each zone is a multifocal element and thus
pupil size should play little or no role in determining final image
quality. However, the pupil size must be greater than 2.5 mm to be
able to experience the multifocal effect. Image contrast is
sacrificed at the near and far distances, to achieve the
intermediate and has an associated loss equivalent to one line of
visual acuity. (Steiner et al., 1999). The ReStor.RTM. lenses, both
the 3.0 and 4.0 versions, provide simultaneous near and distance
vision by a series of concentric, apodized diffractive rings in the
central, three millimeter diameter of the lenses. The mechanism of
diffractive optics should minimize the problems associated with
variable pupil sizes and small amounts of decentration. The
acceptance and implantation of both of these lenses has been
limited by the difficulty experienced with glares, rings, halos,
monocular diplopia, and the contraindication for patients with an
astigmatism of greater than or equal to 2.0 D. (Hansen et al.,
1990; and, Ellingson, 1990). Again precise, preoperative
measurements and accurate IOL power calculations are critical to
the success of the refractive outcome, and neither the ReZoom nor
the ReStor lenses provide an opportunity for secondary power
adjustment post implantation. (Packer et al., 2002).
[0012] One of the newest concepts proposed to tackle the dual
problems of cataracts and presbyopia are through the use of
accommodating IOLs. Two companies, Bausch & Lomb (Rochester,
N.Y.) and Human Optics AG (Erlangen, Germany) have developed IOLs
that attempt to take advantage of the existing accommodative
apparatus of the eye in post implantation patients to treat
presbyopia. Bausch & Lomb's lens offers a plate haptic
configured IOL with a flexible hinged optic (CrystaLens.RTM.).
Human Optics's lens (AKKOMMODATIVE.RTM. 1CU) is similar in design,
but possesses four hinged haptics attached to the edge of the
optic. The accommodative effect of these lenses is caused by the
vaulting of the plate IOL by the contraction of the ciliary body.
This vaulting may be a response of the ciliary body contraction
directly or caused by the associated anterior displacement of the
vitreous body. Initial reports of the efficacy of these two lenses
in clinical trials was quite high with dynamic wavefront
measurement data showing as much as 2 D to 3 D (measured at the
exit pupil of the eye) of accommodation. However, the FDA
Ophthalmic Devices' panel review of Bausch & Lomb's clinical
results concluded that only a 1 D accommodative response (at the
spectacle plane) was significantly achieved by their lens, which is
nearly identical to the pseudo-accommodation values achieved for
simple monofocal IOLs.
[0013] A need exists for an intraocular lens which is adjusted post
operatively in-vivo to form a presbyopia correcting intraocular
lens. This type of lens can be designed in-vivo to correct to an
initial emmetropic state (light from infinity forming a perfect
focus on the retina) and then the presbyopia correction is added
during a second treatment. Such a lens would (1) remove the guess
work involved in presurgical power selection, (2) overcome the
wound healing response inherent to IOL implantation, and (3) allow
the amount of near vision to be customized to correspond to the
patient's requirements. Also, an intraocular lens which is adjusted
post operatively in-vivo to form an aspheric optical element would
result in the patient having an increased depth offocus (DOF),
which allows the patient to see both distance and near (e.g. 40 cm)
through the same lens.
[0014] The techniques of cataract surgery are progressing at an
impressive pace. Generations of phacoemulsification platforms and
more recently introduced surgical lasers keep increasing the
precision of the placement of intraocular lenses (IOLs) and keep
reducing unintended medical outcomes. Nevertheless, after the IOLs
have been implanted, the postsurgical healing process can shift or
tilt the IOLs in a notable fraction of the patients, leading to a
diminished visual acuity, and a deviation from the planned surgical
outcome.
[0015] A new technique has been developed recently to correct or
mitigate such postsurgical IOL shift or tilt. This new technique is
capable of adjusting the optical properties of the IOLs with a
postsurgical procedure to compensate the shift or tilt of the IOL.
As described elsewhere in this patent document and in commonly
owned U.S. Pat. No. 6,905,641, to Platt et al, entitled: "Delivery
system for post-operative power adjustment of adjustable lens",
hereby incorporated by reference in its entirety, the IOLs can be
fabricated from a photo-polymerizable material, henceforth making
them Light Adjustable Lenses, or LALs. In the days after the
surgery, the implanted LALs may shift and tilt, eventually settling
into a postsurgical position different from what the surgeon
planned. At this time, a Light Delivery System (LDD) can be used to
illuminate the LALs with an illumination pattern that induces a
change in the refractive properties of the LALs, such that their
optical performance is modified to compensate the unintended
postsurgical shift or tilt of the LAL.
[0016] Some existing IOLs have a radially varying optical power.
Their optical performance is characterized by an extended depth of
focus (EDOF), and thereby can be helpful to mitigate presbyopia in
patients. Some of these EDOF IOLs are pre-formed before
implantation. Alternatively, the radially varying optical power can
be induced by applying a radially varying illumination pattern
after the LAL was implanted and then settled, as described
elsewhere in this document. While the medical benefit of the EDOF
IOLs is substantial, the effective optical power of these EDOF IOLs
varies with the radius of the pupil of the eye. Thus, as light
conditions vary, such as when transitioning from an indoor
environment to outdoors, as the pupil adapts to the transition, the
optical performance of such EDOF IOLs/LALs changes, which can be
challenging to adapt to for a notable fraction of patients. Also,
since these EDOF IOLs/LALs have an extended focal region instead of
a sharply defined focal point, the image they create on the retina
is experienced by some patients as having some aberrations, being
somewhat blurry.
[0017] Another class of presbyopia-mitigating IOLs has been
described in the commonly owned U.S. Pat. No. 7,281,795, to
Sandstedt et al., entitled: "Light adjustable multifocal lenses",
hereby incorporated by reference in its entirety. This class of
IOLs have a central region with a central optical power and
corresponding central focal point, and a peripheral region with a
peripheral optical power and corresponding peripheral focal point.
Accordingly, these are sometimes referred to as multifocal IOLs.
Typically, the central region is formed for near vision and the
peripheral region for distance vision. Accordingly, the central
optical power is typically 1-3 diopters stronger than the
peripheral optical power. The central region is sometimes referred
to as a "Central Near Add" (CNA) region. As with EDOF IOLs,
multifocal IOLs can also be either pre-formed prior to the surgery,
or can be formed post-surgically, by applying an appropriate
illumination pattern to an implanted LAL.
[0018] These CNA, or multifocal IOLs have the potential to mitigate
presbyopia similarly to multifocal contact lenses. One of the
medical benefits of these multifocal lenses is that their focal
points are well-defined. Therefore, the images they form at the
focal points have only small aberrations. At the same time, one of
the challenges of multifocal IOLs is that the visual acuity
strongly depends on how precisely the CNA region is aligned with
the visual axis of the eye. Even a small decentering of the small
CNA region can induce various aberrations and astigmatism, most
notably coma, and thus can cause a substantial deterioration of the
visual acuity. Since the CNA region is typically quite small, and
the implanted multifocal IOLs also tend to shift and tilt, the
visual acuity of the pre-formed multifocal IOLs often deteriorates
as they shift and de-center after implantation.
[0019] There are several possible sources of decentering. In cases,
where the central region is formed prior to implantation, such as
molded into an IOL, or into a LAL, the postsurgical shifts of the
IOL/LAL can lead to a correspondingly decentered central region. In
cases, where the central region is formed after the implantation by
illuminating the LAL with a suitable illumination pattern, another
issue can lead to the same problem. The LALs are illuminated after
the iris of the eye is substantially dilated, in order to
accommodate the entire illumination pattern. In some cases, the
illumination pattern to form the CNA region can be centered on the
geometric axis of the LAL. Less typically, the illumination pattern
can be centered on the dilated iris. In either case, subsequently
the iris often returns to its natural, non-dilated state
non-symmetrically, thus shifting the visual axis of the eye. Thus,
the CNA region that was centered either on the geometric LAL axis,
or on the dilated iris, may end up being notably decentered from
the visual axis of the eye, defined by the non-dilated iris.
[0020] The problematic visual acuity of the decentered central CNA
region is probably one of the causes why existing CNA/multifocal
IOLs achieved only limited market acceptance. It is mentioned that
the Central Near Add concept has been also implemented in related
ophthalmic technologies: as implanted small corneal inlays, and as
CNA contact lenses. These technologies also suffer from the
analogous problem of postsurgical shift and decentration.
[0021] For at least the above reasons, there is a pressing medical
need for the following improvement in the field of
presbyopia-mitigating IOLs/LALs. (1) A new class of IOLs/LALs that
deliver the presbyopia-mitigating medical benefits of the EDOF and
the CNA/multifocal designs, while limiting or minimizing the
undesirable aspects of their optical performance. (2) LALs/IOLs,
whose CNA region is aligned with the visual axis of the eye in the
non-dilated state of the iris.
SUMMARY
[0022] General embodiments of the present invention provide a first
optical element whose properties may be adjusted post-manufacture
to produce a second optical element, wherein the second optical
element is capable of providing an increased depth of focus to a
patient. Specifically, the invention relates to a spherical
intraocular lens that is capable of being transformed
post-operatively into an aspheric optical element. Through this
approach, the intraocular and/or focal zones of the aspheric
optical element can be more precisely adjusted after the lens has
been subjected to any post-operative migration. Also, the
adjustment of the aspheric optical element can be based on input
from the patient and/or the adjustment of the aspheric optical
element can be accomplished through standard refraction techniques
rather than making the adjustment through preoperative
estimation.
[0023] The alteration of the spherical IOL is accomplished via a
modifying composition ("MC") dispersed throughout the spherical
IOL. The MC is capable of polymerization when exposed to an
external stimulus such as heat or light. The stimulus can be
directed to one or more regions of the element causing
polymerization of the MC only in the exposed regions. The
polymerization of the MC causes changes in the optical properties
of the element within the exposed regions. In some embodiments, the
optical properties changed though the polymerization of the MC
include a change in the radius of curvature and/or a change in the
refractive index.
[0024] The method for providing an aspheric lens begins with the
formation of the first polymer matrix in the presence of the
modifying composition. The next step is the formation of a second
polymer matrix comprising polymerized MC. The formation of this
polymer network changes the optical properties of the element,
namely the refractive index. In addition, when the MC is
polymerized to form the second polymer matrix, a gradient or a
difference in the chemical potential between the polymerized and
unpolymerized regions is induced. This in turn causes the
unpolymerized MC to diffuse within the element, which reestablishes
a thermodynamic equilibrium within the optical element. If the
optical element possesses sufficient elasticity, this migration of
MC can cause swelling of the element in the area exposed to the
stimulus. This, in turn, changes the shape of the element, causing
changes in the optical properties (i.e., radius of curvature and/or
refractive index). Whether the radius of curvature of the element
and/or the refractive index of the element change depends upon (1)
the nature of the optical element, (2) the MC incorporated into the
element, (3) the duration that the element is exposed to a
stimulus, and (4) the spatial intensity profile of the
stimulus.
[0025] By controlling the radiant exposure (i.e., beam irradiance
and duration), spatial irradiance profile, and target area,
physical changes in the radius of curvature of the lens surface are
achieved, thereby modifying the refractive power of an implanted
lens (1) to correct spherical refractive errors, (2) to correct
sphero-cylindrical refractive errors, (3) to induce a targeted
amount of asphericity and/or a combination thereof. Once the
appropriate refractive adjustment is achieved, the entire aspheric
lens is irradiated to polymerize the remaining unreacted MC under
conditions that prevent any additional change in lens power. By
irradiating the entire lens, MC diffusion is prevented thus no
change in lens power results. This second irradiation procedure is
referred to as "lock-in".
[0026] In another aspect of the present invention, the optical
elements are self-contained in that once fabricated, no material is
either added or removed from the lens to obtain the desired optical
properties.
[0027] The above described medical needs are further addressed by
the following embodiments of Light Adjustable Lenses. Some
embodiments of a Light Adjustable Lens (LAL) can comprise a central
region, centered on a central axis, having a position-dependent
central optical power, and; a peripheral annulus, centered on an
annulus axis and surrounding the central region, having a
position-dependent peripheral optical power; wherein an average of
the central optical power is at least 0.5 diopters different from
an average of the peripheral optical power, and the central axis is
laterally shifted relative to the annulus axis.
[0028] In some embodiments, a Light Adjustable Lens (LAL) comprises
a light-adjusted region, centered on an adjustment axis and having
a position-dependent optical power; wherein the adjustment axis is
laterally shifted relative to a LAL axis of the LAL.
[0029] In some embodiments, a method of adjusting a Light
Adjustable Lens (LAL) comprises the steps of: implanting a LAL into
an eye; applying a first illumination to the LAL with a first
illumination pattern to induce a position-dependent peripheral
optical power in at least a peripheral annulus, centered on an
annulus axis; determining a central region and a corresponding
central axis of the LAL; and applying a second illumination to the
LAL with a second illumination pattern to induce a
position-dependent central optical power in the central region of
the LAL; wherein the central axis is laterally shifted relative to
the annulus axis, and an average of the central optical power is at
least 0.5 diopters different from than an average of the peripheral
optical power.
[0030] In some embodiments, a method of adjusting a Light
Adjustable Lens (LAL) comprises the steps of: implanting a LAL into
an eye, the LAL having a pre-molded position-dependent peripheral
optical power in at least a peripheral annulus, centered on an
annulus axis; determining a central region and a corresponding
central axis of the LAL; and applying a central illumination to the
LAL with a central illumination pattern to induce a
position-dependent central optical power in the central region of
the LAL; wherein the central axis is laterally shifted relative to
the annulus axis, and an average of the central optical power is at
least 0.5 diopters different from than an average of the peripheral
optical power.
[0031] In some embodiments, a method of adjusting a Light
Adjustable Lens (LAL) comprises the steps of: implanting a LAL,
having a LAL axis, into an eye; and applying an illumination to the
LAL with an illumination pattern to induce a position-dependent
optical power in a light-adjusted region, centered on an adjustment
axis; wherein the adjustment axis is laterally shifted relative to
the LAL axis.
[0032] In some embodiments, a method of adjusting a Light
Adjustable Lens (LAL) comprises the steps of: causing an LAL,
implanted into an eye, to induce a first depth of focus of the
ophthalmic optical system; determining a central region and a
corresponding central axis of the LAL; and illuminating the LAL
with an illumination pattern centered on the central axis to induce
a second depth of focus of the ophthalmic optical system; wherein
the central axis is laterally shifted relative to a LAL axis, and
the second depth of focus is at least 0.5 diopters greater than the
first depth of focus.
[0033] 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
[0034] For a more complete understanding of the present invention,
reference is now made to the following descriptions taken in
conjunction with the accompanying drawing.
[0035] FIG. 1 shows a schematic representation of the depth of
focus.
[0036] FIG. 2 shows a collimated beam of light being refracted by a
spherical lens.
[0037] FIG. 3 shows a schematic of the adaptive optics simulator
used to determine the optimized values for 4.sup.th order spherical
aberration and defocus.
[0038] FIG. 4 shows a schematic of positive power adjustment
mechanism; wherein (a) is a schematic representation of selective
irradiation of the central zone of the lens in which the
polymerization of the MC creates a difference in the chemical
potential between the irradiated and non-irradiated regions, (b) to
reestablish equilibrium, excess MC diffuses into the irradiated
region causing swelling, and (c) irradiation of the entire lens
"locks" the remaining MC and the shape change.
[0039] FIG. 5 shows a plot of the aspheric function described in
Equation 1.
[0040] FIG. 6 shows cross-sectional plots of Equation 2 generated
by combining a power neutral profile with weighted amounts
(.beta.=0 to 0.57) of the aspheric profile.
[0041] FIG. 7 shows a plot of induced 4.sup.th and 6.sup.th order
spherical aberration as a function of increasing .beta. value. The
measurement aperture was 4 mm and none of these LALs received any
type of prior adjustment.
[0042] FIG. 8 shows a plot of induced 4.sup.th and 6.sup.th order
spherical aberration as a function of increasing .beta. value for
LALs receiving a hyperopic, myopic, and no prior adjustment. The
measurement aperture for both the 4.sup.th and 6.sup.th order
spherical aberration was 4 mm.
[0043] FIG. 9 shows the monocular visual acuity data for eyes
receiving an initial refractive adjustment followed by an aspheric
treatment (n=32) versus those eyes treated only for distance
emmetropia (n=12).
[0044] FIG. 10 shows the segregation of the monocular visual acuity
data into high (n=9) and low (n=23) induced spherical aberration
values. For comparison, those eyes (n=12) adjusted for distance
emmetropia are also shown.
[0045] FIG. 11 shows a comparison of the monocular and the
binocular visual acuities for a series of patients that were
corrected for distance emmetropia in one eye and received an
aspheric treatment in their fellow eye. The amount of induced
asphericity ranged from -0.04 .mu.m to -0.10 .mu.m, referenced to a
4 mm pupil.
[0046] FIG. 12 shows a comparison of the monocular and binocular
visual acuities for a series of patients that were corrected for
distance emmetropia in one eye and received an aspheric treatment
in their fellow eye. The amount of induced asphericity ranged from
-0.11 .mu.m to -0.23 .mu.m, referenced to a 4 mm pupil.
[0047] FIGS. 13A-D illustrate a Light Adjustable Lens with
position-dependent optical power and shifted axes, and stages of an
illumination of the Light Adjustable Lens.
[0048] FIGS. 14A-B illustrate a Light Adjustable Lens with
position-dependent optical power and shifted axes.
[0049] FIGS. 15A-C illustrate a position dependent optical power in
a LAL.
[0050] FIG. 16 illustrates a Light Adjustable Lens with
position-dependent optical power.
[0051] FIGS. 17A-B illustrate the visual acuity of presbyopic eyes,
with implanted EDOF or CNA LALs.
[0052] FIG. 18 illustrates the visual acuity of presbyopic eyes,
with implanted EDOF+CNA LALs.
[0053] FIG. 19 illustrates a Light Adjustable Lens with a
peripheral optical power of differently-curved radial dependence
compared to FIG. 1.
[0054] FIGS. 20A-C illustrate Light Adjustable Lenses with an
average central optical power less than an average peripheral
optical power, with various radial dependence curvatures.
[0055] FIGS. 21A-B illustrate a LAL with a mid-range vision
region.
[0056] FIG. 22 illustrates a LAL with a light-adjusted region, with
a shifted adjustment axis.
[0057] FIG. 23 illustrates the position dependent optical power of
a LAL.
[0058] FIG. 24 illustrates a method of adjusting the LAL.
[0059] FIGS. 25A-B illustrate applying the first illumination and
the second illumination to the LAL within the method.
[0060] FIG. 26 illustrates applying a third illumination to the
LAL.
[0061] FIGS. 27A-B illustrate applying the second and third
illumination to the LAL.
[0062] FIG. 28 illustrates a method of adjusting the LAL with a
pre-molded LAL.
[0063] FIG. 29 illustrates a generalized method of adjusting the
LAL.
[0064] FIG. 30 illustrates a method of adjusting the LAL.
DETAILED DESCRIPTION
[0065] As used herein the specification, "a" or "an" may mean one
or more. As used herein in the claim(s), when used in conjunction
with the word "comprising", the words "a" or "an" may mean one or
more than one. As used herein "another" may mean at least a second
or more. Furthermore, as used herein, the terms "comprise," "have"
and "include" are open-ended linking verbs. Any forms or tenses of
one or more of these verbs, such as "comprises," "comprising,"
"has," "having," "includes" and "including," are also open-ended.
For example, any method that "comprises," "has" or "includes" one
or more steps is not limited to possessing only those one or more
steps and also covers other unlisted steps.
[0066] Throughout this application, the term "about" is used to
indicate that a value includes the inherent variation of error for
the device, the method being employed to determine the value, or
the variation that exists among the experimental test articles.
Chemical Group Definitions
[0067] When used in the context of a chemical group, "hydrogen"
means --H; "hydroxy" means --OH; "oxo" means .dbd.O; "halo" means
independently --F, --Cl, --Br or --I; "amino" means --NH.sub.2 (see
below for definitions of groups containing the term amino, e.g.,
alkylamino); "hydroxyamino" means --NHOH; "nitro" means --NO.sub.2;
imino means .dbd.NH (see below for definitions of groups containing
the term imino, e.g., alkylimino); "cyano" means --CN; "isocyanate"
means --N.dbd.C.dbd.O; "azido" means --N.sub.3; in a monovalent
context "phosphate" means --OP(O)(OH).sub.2 or a deprotonated form
thereof, in a divalent context "phosphate" means --OP(O)(OH)O-- or
a deprotonated form thereof, "mercapto" means --SH; and "thio"
means .dbd.S
[0068] In the context of chemical formulas, the symbol "-" means a
single bond, "=" means a double bond, and ".ident." means triple
bond. The symbol "----" represents an optional bond, which if
present is either single or double. The symbol "" represents a
single bond or a double bond. Thus, for example, the structure
##STR00001##
includes the structures
##STR00002##
[0069] As will be understood by a person of skill in the art, no
one such ring atom forms part of more than one double bond. The
symbol "", when drawn perpendicularly across a bond indicates a
point of attachment of the group. It is noted that the point of
attachment is typically only identified in this manner for larger
groups in order to assist the reader in rapidly and unambiguously
identifying a point of attachment. The symbol "" means a single
bond where the group attached to the thick end of the wedge is "out
of the page." The symbol "" means a single bond where the group
attached to the thick end of the wedge is "into the page". The
symbol "" means a single bond where the conformation (e.g., either
R or S) or the geometry is undefined (e.g., either E or Z).
[0070] Any undefined valency on an atom of a structure shown in
this application implicitly represents a hydrogen atom bonded to
the atom. When a group "R" is depicted as a "floating group" on a
ring system, for example, in the formula:
##STR00003##
[0071] then R may replace any hydrogen atom attached to any of the
ring atoms, including a depicted, implied, or expressly defined
hydrogen, so long as a stable structure is formed. When a group "R"
is depicted as a "floating group" on a fused ring system, as for
example in the formula:
##STR00004##
[0072] then R may replace any hydrogen attached to any of the ring
atoms of either of the fused rings unless specified otherwise.
Replaceable hydrogens include depicted hydrogens (e.g., the
hydrogen attached to the nitrogen in the formula above), implied
hydrogens (e.g., a hydrogen of the formula above that is not shown
but understood to be present), expressly defined hydrogens, and
optional hydrogens whose presence depends on the identity of a ring
atom (e.g., a hydrogen attached to group X, when X equals --CH--),
so long as a stable structure is formed. In the example depicted, R
may reside on either the 5-membered or the 6-membered ring of the
fused ring system. In the formula above, the subscript letter "y"
immediately following the group "R" enclosed in parentheses,
represents a numeric variable. Unless specified otherwise, this
variable can be 0, 1, 2, or any integer greater than 2, only
limited by the maximum number of replaceable hydrogen atoms of the
ring or ring system.
[0073] For the groups and classes below, the following
parenthetical subscripts further define the group/class as follows:
"(Cn)" defines the exact number (n) of carbon atoms in the
group/class. "(C.ltoreq.n)" defines the maximum number (n) of
carbon atoms that can be in the group/class, with the minimum
number as small as possible for the group in question, e.g., it is
understood that the minimum number of carbon atoms in the group
"alkenyl.sub.(C.ltoreq.8)" or the class "alkene.sub.(C.ltoreq.8)"
is two. For example, "alkoxy.sub.(C.ltoreq.10)" designates those
alkoxy groups having from 1 to 10 carbon atoms (e.g., 1, 2, 3, 4,
5, 6, 7, 8, 9, or 10, or any range derivable therein (e.g., 3 to 10
carbon atoms). (Cn-n') defines both the minimum (n) and maximum
number (n') of carbon atoms in the group. Similarly,
"alkyl.sub.(C2-10)" designates those alkyl groups having from 2 to
10 carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any range
derivable therein (e.g., 3 to 10 carbon atoms)).
[0074] The term "saturated" as used herein means the compound or
group so modified has no carbon-carbon double and no carbon-carbon
triple bonds, except as noted below. The term does not preclude
carbon-heteroatom multiple bonds, for example a carbon oxygen
double bond or a carbon nitrogen double bond. Moreover, it does not
preclude a carbon-carbon double bond that may occur as part of
keto-enol tautomerism or imine/enamine tautomerism.
[0075] The term "aliphatic" when used without the "substituted"
modifier signifies that the compound/group so modified is an
acyclic or cyclic, but non-aromatic hydrocarbon compound or group.
In aliphatic compounds/groups, the carbon atoms can be joined
together in straight chains, branched chains, or non-aromatic rings
(alicyclic). Aliphatic compounds/groups can be saturated, that is
joined by single bonds (alkanes/alkyl), or unsaturated, with one or
more double bonds (alkenes/alkenyl) or with one or more triple
bonds (alkynes/alkynyl). When the term "aliphatic" is used without
the "substituted" modifier only carbon and hydrogen atoms are
present. When the term is used with the "substituted" modifier one
or more hydrogen atom has been independently replaced by --OH, --F,
--Cl, --Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H,
--CO.sub.2CH.sub.3, --CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3,
--C(O)CH.sub.3, --N(CH.sub.3).sub.2, --C(O)NH.sub.2,
--OC(O)CH.sub.3, or --S(O).sub.2NH.sub.2.
[0076] The term "alkyl" when used without the "substituted"
modifier refers to a monovalent saturated aliphatic group with a
carbon atom as the point of attachment, a linear or branched,
cyclo, cyclic or acyclic structure, and no atoms other than carbon
and hydrogen. Thus, as used herein cycloalkyl is a subset of alkyl.
The groups --CH.sub.3 (Me), --CH.sub.2CH.sub.3 (Et),
--CH.sub.2CH.sub.2CH.sub.3 (n-Pr), --CH(CH.sub.3).sub.2 (iso-Pr),
--CH(CH.sub.2).sub.2 (cyclopropyl),
--CH.sub.2CH.sub.2CH.sub.2CH.sub.3 (n-Bu),
--CH(CH.sub.3)CH.sub.2CH.sub.3 (sec-butyl),
--CH.sub.2CH(CH.sub.3).sub.2 (iso-butyl), --C(CH.sub.3).sub.3
(tert-butyl), --CH.sub.2C(CH.sub.3).sub.3 (neo-pentyl), cyclobutyl,
cyclopentyl, cyclohexyl, and cyclohexylmethyl are non-limiting
examples of alkyl groups. The term "alkanediyl" when used without
the "substituted" modifier refers to a divalent saturated aliphatic
group, with one or two saturated carbon atom(s) as the point(s) of
attachment, a linear or branched, cyclo, cyclic or acyclic
structure, no carbon-carbon double or triple bonds, and no atoms
other than carbon and hydrogen. The groups, --CH.sub.2--
(methylene), --CH.sub.2CH.sub.2--,
--CH.sub.2C(CH.sub.3).sub.2CH.sub.2--,
--CH.sub.2CH.sub.2CH.sub.2--, and
##STR00005##
are non-limiting examples of alkanediyl groups. The term
"alkylidene" when used without the "substituted" modifier refers to
the divalent group .dbd.CRR' in which R and R' are independently
hydrogen, alkyl, or R and R' are taken together to represent an
alkanediyl having at least two carbon atoms. Non-limiting examples
of alkylidene groups include: .dbd.CH.sub.2,
.dbd.CH(CH.sub.2CH.sub.3), and .dbd.C(CH.sub.3).sub.2. When any of
these terms is used with the "substituted" modifier one or more
hydrogen atom has been independently replaced by --OH, --F, --Cl,
--Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3,
--CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. The following groups are non-limiting
examples of substituted alkyl groups: --CH.sub.2OH, --CH.sub.2Cl,
--CF.sub.3, --CH.sub.2CN, --CH.sub.2C(O)OH,
--CH.sub.2C(O)OCH.sub.3, --CH.sub.2C(O)NH.sub.2,
--CH.sub.2C(O)CH.sub.3, --CH.sub.2OCH.sub.3,
--CH.sub.2OC(O)CH.sub.3, --CH.sub.2NH.sub.2,
--CH.sub.2N(CH.sub.3).sub.2, and --CH.sub.2CH.sub.2Cl. The term
"haloalkyl" is a subset of substituted alkyl, in which one or more
hydrogen has been substituted with a halo group and no other atoms
aside from carbon, hydrogen and halogen are present. The group,
--CH.sub.2Cl is a non-limiting examples of a haloalkyl. An "alkane"
refers to the compound H--R, wherein R is alkyl. The term
"fluoroalkyl" is a subset of substituted alkyl, in which one or
more hydrogen has been substituted with a fluoro group and no other
atoms aside from carbon, hydrogen and fluorine are present. The
groups, --CH.sub.2F, --CF.sub.3, and --CH.sub.2CF.sub.3 are
non-limiting examples of fluoroalkyl groups. An "alkane" refers to
the compound H--R, wherein R is alkyl.
[0077] The term "alkenyl" when used without the "substituted"
modifier refers to an monovalent unsaturated aliphatic group with a
carbon atom as the point of attachment, a linear or branched,
cyclo, cyclic or acyclic structure, at least one nonaromatic
carbon-carbon double bond, no carbon-carbon triple bonds, and no
atoms other than carbon and hydrogen. Non-limiting examples of
alkenyl groups include: --CH.dbd.CH.sub.2 (vinyl),
--CH.dbd.CHCH.sub.3, --CH.dbd.CHCH.sub.2CH.sub.3,
--CH.sub.2CH.dbd.CH.sub.2 (allyl), --CH.sub.2CH.dbd.CHCH.sub.3, and
--CH.dbd.CH--C.sub.6H.sub.5. The term "alkenediyl" when used
without the "substituted" modifier refers to a divalent unsaturated
aliphatic group, with two carbon atoms as points of attachment, a
linear or branched, cyclo, cyclic or acyclic structure, at least
one nonaromatic carbon-carbon double bond, no carbon-carbon triple
bonds, and no atoms other than carbon and hydrogen. The groups,
--CH.dbd.CH--, --CH.dbd.C(CH.sub.3)CH.sub.2--,
--CH.dbd.CHCH.sub.2--, and
##STR00006##
are non-limiting examples of alkenediyl groups. When these terms
are used with the "substituted" modifier one or more hydrogen atom
has been independently replaced by --OH, --F, --Cl, --Br, --I,
--NH.sub.2, --NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN,
--SH, --OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. The groups, --CH.dbd.CHF, --CH.dbd.CHCl and
--CH.dbd.CHBr, are non-limiting examples of substituted alkenyl
groups. An "alkene" refers to the compound H--R, wherein R is
alkenyl.
[0078] The term "alkynyl" when used without the "substituted"
modifier refers to an monovalent unsaturated aliphatic group with a
carbon atom as the point of attachment, a linear or branched,
cyclo, cyclic or acyclic structure, at least one carbon-carbon
triple bond, and no atoms other than carbon and hydrogen. As used
herein, the term alkynyl does not preclude the presence of one or
more non-aromatic carbon-carbon double bonds. The groups,
--C.ident.CH, --C.ident.CCH.sub.3, and --CH.sub.2C.ident.CCH.sub.3,
are non-limiting examples of alkynyl groups. The term "alkynediyl"
when used without the "substituted" modifier refers to a divalent
unsaturated aliphatic group, with two carbon atoms as points of
attachment, a linear or branched, cyclo, cyclic or acyclic
structure, at least one carbon-carbon triple bond, and no atoms
other than carbon and hydrogen. When these terms are used with the
"substituted" modifier one or more hydrogen atom has been
independently replaced by --OH, --F, --Cl, --Br, --I, --NH.sub.2,
--NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN, --SH,
--OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. An "alkyne" refers to the compound H--R,
wherein R is alkynyl.
[0079] The term "aryl" when used without the "substituted" modifier
refers to a monovalent unsaturated aromatic group with an aromatic
carbon atom as the point of attachment, said carbon atom forming
part of a one or more six-membered aromatic ring structure, wherein
the ring atoms are all carbon, and wherein the group consists of no
atoms other than carbon and hydrogen. If more than one ring is
present, the rings may be fused or unfused. As used herein, the
term does not preclude the presence of one or more alkyl group
(carbon number limitation permitting) attached to the first
aromatic ring or any additional aromatic ring present. Non-limiting
examples of aryl groups include phenyl (Ph), methylphenyl,
(dimethyl)phenyl, --C.sub.6H.sub.4CH.sub.2CH.sub.3 (ethylphenyl),
naphthyl, and the monovalent group derived from biphenyl. The term
"arenediyl" when used without the "substituted" modifier refers to
a divalent aromatic group, with two aromatic carbon atoms as points
of attachment, said carbon atoms forming part of one or more
six-membered aromatic ring structure(s) wherein the ring atoms are
all carbon, and wherein the monovalent group consists of no atoms
other than carbon and hydrogen. As used herein, the term does not
preclude the presence of one or more alkyl group (carbon number
limitation permitting) attached to the first aromatic ring or any
additional aromatic ring present. If more than one ring is present,
the rings may be fused or unfused. Non-limiting examples of
arenediyl groups include:
##STR00007##
[0080] When these terms are used with the "substituted" modifier
one or more hydrogen atom has been independently replaced by --OH,
--F, --Cl, --Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H,
--CO.sub.2CH.sub.3, --CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3,
--C(O)CH.sub.3, --N(CH.sub.3).sub.2, --C(O)NH.sub.2,
--OC(O)CH.sub.3, or --S(O).sub.2NH.sub.2. An "arene" refers to the
compound H--R, wherein R is aryl.
[0081] The term "aralkyl" when used without the "substituted"
modifier refers to the monovalent group -alkanediyl-aryl, in which
the terms alkanediyl and aryl are each used in a manner consistent
with the definitions provided above. Non-limiting examples of
aralkyls are: phenylmethyl (benzyl, Bn) and 2-phenyl-ethyl. When
the term is used with the "substituted" modifier one or more
hydrogen atom from the alkanediyl and/or the aryl has been
independently replaced by --OH, --F, --Cl, --Br, --I, --NH.sub.2,
--NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN, --SH,
--OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. Non-limiting examples of substituted aralkyls
are: (3-chlorophenyl)-methyl, and 2-chloro-2-phenyl-eth-1-yl.
[0082] The term "heteroaryl" when used without the "substituted"
modifier refers to a monovalent aromatic group with an aromatic
carbon atom or nitrogen atom as the point of attachment, said
carbon atom or nitrogen atom forming part of an aromatic ring
structure wherein at least one of the ring atoms is nitrogen,
oxygen or sulfur, and wherein the group consists of no atoms other
than carbon, hydrogen, aromatic nitrogen, aromatic oxygen and
aromatic sulfur. As used herein, the term does not preclude the
presence of one or more alkyl group (carbon number limitation
permitting) attached to the aromatic ring or any additional
aromatic ring present. Non-limiting examples of heteroaryl groups
include furanyl, imidazolyl, indolyl, indazolyl (Im),
methylpyridyl, oxazolyl, pyridyl, pyrrolyl, pyrimidyl, pyrazinyl,
quinolyl, quinazolyl, quinoxalinyl, thienyl, and triazinyl. The
term "heteroarenediyl" when used without the "substituted" modifier
refers to an divalent aromatic group, with two aromatic carbon
atoms, two aromatic nitrogen atoms, or one aromatic carbon atom and
one aromatic nitrogen atom as the two points of attachment, said
atoms forming part of one or more aromatic ring structure(s)
wherein at least one of the ring atoms is nitrogen, oxygen or
sulfur, and wherein the divalent group consists of no atoms other
than carbon, hydrogen, aromatic nitrogen, aromatic oxygen and
aromatic sulfur. As used herein, the term does not preclude the
presence of one or more alkyl group (carbon number limitation
permitting) attached to the first aromatic ring or any additional
aromatic ring present. If more than one ring is present, the rings
may be fused or unfused. Non-limiting examples of heteroarenediyl
groups include:
##STR00008##
[0083] When these terms are used with the "substituted" modifier
one or more hydrogen atom has been independently replaced by --OH,
--F, --Cl, --Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H,
--CO.sub.2CH.sub.3, --CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3,
--C(O)CH.sub.3, --N(CH.sub.3).sub.2, --C(O)NH.sub.2,
--OC(O)CH.sub.3, or --S(O).sub.2NH.sub.2.
[0084] The term "acyl" when used without the "substituted" modifier
refers to the group --C(O)R, in which R is a hydrogen, alkyl, aryl,
aralkyl or heteroaryl, as those terms are defined above. The
groups, --CHO, --C(O)CH.sub.3 (acetyl, Ac), --C(O)CH.sub.2CH.sub.3,
--C(O)CH.sub.2CH.sub.2CH.sub.3, --C(O)CH(CH.sub.3).sub.2,
--C(O)CH(CH.sub.2).sub.2, --C(O)C.sub.6H.sub.5,
--C(O)C.sub.6H.sub.4CH.sub.3, --C(O)CH.sub.2C.sub.6H.sub.5,
--C(O)(imidazolyl) are non-limiting examples of acyl groups. A
"thioacyl" is defined in an analogous manner, except that the
oxygen atom of the group --C(O)R has been replaced with a sulfur
atom, --C(S)R. When either of these terms are used with the
"substituted" modifier one or more hydrogen atom has been
independently replaced by --OH, --F, --Cl, --Br, --I, --NH.sub.2,
--NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN, --SH,
--OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. The groups, --C(O)CH.sub.2CF.sub.3,
--CO.sub.2H (carboxyl), --CO.sub.2CH.sub.3 (methylcarboxyl),
--CO.sub.2CH.sub.2CH.sub.3, --C(O)NH.sub.2 (carbamoyl), and
--CON(CH.sub.3).sub.2, are non-limiting examples of substituted
acyl groups.
[0085] The term "alkoxy" when used without the "substituted"
modifier refers to the group --OR, in which R is an alkyl, as that
term is defined above. Non-limiting examples of alkoxy groups
include: --OCH.sub.3, --OCH.sub.2CH.sub.3,
--OCH.sub.2CH.sub.2CH.sub.3, --OCH(CH.sub.3).sub.2,
--OCH(CH.sub.2).sub.2, --O-cyclopentyl, and --O-cyclohexyl. The
terms "alkenyloxy", "alkynyloxy", "aryloxy", "aralkoxy",
"heteroaryloxy", and "acyloxy", when used without the "substituted"
modifier, refers to groups, defined as --OR, in which R is alkenyl,
alkynyl, aryl, aralkyl, heteroaryl, and acyl, respectively.
Similarly, the term "alkylthio" when used without the "substituted"
modifier refers to the group --SR, in which R is an alkyl, as that
term is defined above. When any of these terms is used with the
"substituted" modifier one or more hydrogen atom has been
independently replaced by --OH, --F, --Cl, --Br, --I, --NH.sub.2,
--NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN, --SH,
--OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2. The term "alcohol" corresponds to an alkane,
as defined above, wherein at least one of the hydrogen atoms has
been replaced with a hydroxy group.
[0086] The term "alkylamino" when used without the "substituted"
modifier refers to the group --NHR, in which R is an alkyl, as that
term is defined above. Non-limiting examples of alkylamino groups
include: --NHCH.sub.3 and --NHCH.sub.2CH.sub.3. The term
"dialkylamino" when used without the "substituted" modifier refers
to the group --NRR', in which R and R' can be the same or different
alkyl groups, or R and R' can be taken together to represent an
alkanediyl. Non-limiting examples of dialkylamino groups include:
--N(CH.sub.3).sub.2, --N(CH.sub.3)(CH.sub.2CH.sub.3), and
N-pyrrolidinyl. The terms "alkoxyamino", "alkenylamino",
"alkynylamino", "arylamino", "aralkylamino", "heteroarylamino", and
"alkylsulfonylamino" when used without the "substituted" modifier,
refers to groups, defined as --NHR, in which R is alkoxy, alkenyl,
alkynyl, aryl, aralkyl, heteroaryl, and alkylsulfonyl,
respectively. A non-limiting example of an arylamino group is
--NHC.sub.6H.sub.5. The term "amido" (acylamino), when used without
the "substituted" modifier, refers to the group --NHR, in which R
is acyl, as that term is defined above. A non-limiting example of
an amido group is --NHC(O)CH.sub.3. The term "alkylimino" when used
without the "substituted" modifier refers to the divalent group
.dbd.NR, in which R is an alkyl, as that term is defined above.
When any of these terms is used with the "substituted" modifier one
or more hydrogen atom has been independently replaced by --OH, --F,
--Cl, --Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H,
--CO.sub.2CH.sub.3, --CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3,
--C(O)CH.sub.3, --N(CH.sub.3).sub.2, --C(O)NH.sub.2,
--OC(O)CH.sub.3, or --S(O).sub.2NH.sub.2. The groups
--NHC(O)OCH.sub.3 and --NHC(O)NHCH.sub.3 are non-limiting examples
of substituted amido groups.
[0087] The term "alkylphosphate" when used without the
"substituted" modifier refers to the group --OP(O)(OH)(OR), in
which R is an alkyl, as that term is defined above. Non-limiting
examples of alkylphosphate groups include: --OP(O)(OH)(OMe) and
--OP(O)(OH)(OEt). The term "dialkylphosphate" when used without the
"substituted" modifier refers to the group --OP(O)(OR)(OR'), in
which R and R' can be the same or different alkyl groups, or R and
R' can be taken together to represent an alkanediyl. Non-limiting
examples of dialkylphosphate groups include: --OP(O)(OMe).sub.2,
--OP(O)(OEt)(OMe) and --OP(O)(OEt).sub.2. When any of these terms
is used with the "substituted" modifier one or more hydrogen atom
has been independently replaced by --OH, --F, --Cl, --Br, --I,
--NH.sub.2, --NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3, --CN,
--SH, --OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2.
[0088] The terms "alkylsulfonyl" and "alkylsulfinyl" when used
without the "substituted" modifier refers to the groups
--S(O).sub.2R and --S(O)R, respectively, in which R is an alkyl, as
that term is defined above. The terms "alkenylsulfonyl",
"alkynylsulfonyl", "arylsulfonyl", "aralkylsulfonyl", and
"heteroarylsulfonyl", are defined in an analogous manner. When any
of these terms is used with the "substituted" modifier one or more
hydrogen atom has been independently replaced by --OH, --F, --Cl,
--Br, --I, --NH.sub.2, --NO.sub.2, --CO.sub.2H, --CO.sub.2CH.sub.3,
--CN, --SH, --OCH.sub.3, --OCH.sub.2CH.sub.3, --C(O)CH.sub.3,
--N(CH.sub.3).sub.2, --C(O)NH.sub.2, --OC(O)CH.sub.3, or
--S(O).sub.2NH.sub.2.
[0089] The term "effective," as that term is used in the
specification and/or claims, means adequate to accomplish a
desired, expected, or intended result. "Effective amount," or
"Therapeutically effective amount" when used in the context of
treating a patient or subject with a stimulus means that the amount
of the stimulus which, when administered to a subject or patient
for treating a condition, is sufficient to effect such treatment
for the condition.
[0090] As used herein, the term "patient" or "subject" refers to a
living mammalian organism, such as a human, monkey, cow, sheep,
goat, dog, cat, mouse, rat, guinea pig, or transgenic species
thereof. In certain embodiments, the patient or subject is a
primate. Non-limiting examples of human subjects are adults,
juveniles, infants and fetuses.
[0091] As generally used herein "pharmaceutically acceptable"
refers to those compounds, materials, compositions, and/or dosage
forms which are, within the scope of sound medical judgment,
suitable for use in contact with the tissues, organs, and/or bodily
fluids of human beings and animals without excessive toxicity,
irritation, allergic response, or other problems or complications
commensurate with a reasonable benefit/risk ratio.
[0092] A "repeat unit" is the simplest structural entity of certain
materials, for example, frameworks and/or polymers, whether
organic, inorganic or metal-organic. In the case of a polymer
chain, repeat units are linked together successively along the
chain, like the beads of a necklace. For example, in polyethylene,
--[--CH.sub.2CH.sub.2-].sub.n-, the repeat unit is
--CH.sub.2CH.sub.2--. The subscript "n" denotes the degree of
polymerization, that is, the number of repeat units linked
together. When the value for "n" is left undefined or where "n" is
absent, it simply designates repetition of the formula within the
brackets as well as the polymeric nature of the material. The
concept of a repeat unit applies equally to where the connectivity
between the repeat units extends three dimensionally, such as in,
modified polymers, thermosetting polymers, etc.
[0093] "Treatment" or "treating" includes (1) inhibiting a disease
in a subject or patient experiencing or displaying the pathology or
symptomatology of the disease (e.g., arresting further development
of the pathology and/or symptomatology), (2) ameliorating a disease
in a subject or patient that is experiencing or displaying the
pathology or symptomatology of the disease (e.g., reversing the
pathology and/or symptomatology), and/or (3) effecting any
measurable decrease in a disease in a subject or patient that is
experiencing or displaying the pathology or symptomatology of the
disease.
[0094] The above definitions supersede any conflicting definition
in any of the reference that is incorporated by reference herein.
The fact that certain terms are defined, however, should not be
considered as indicative that any term that is undefined is
indefinite. Rather, all terms used are believed to describe the
invention in terms such that one of ordinary skill can appreciate
the scope and practice the present invention.
Compositions of the Invention
[0095] Compositions of the present disclosure may be made using the
methods described above and in Example 1 below. These methods can
be further modified and optimized using the principles and
techniques of organic chemistry and/or polymer chemistry as applied
by a person skilled in the art. Such principles and techniques are
taught, for example, in March's Advanced Organic Chemistry:
Reactions, Mechanisms, and Structure (2007), and/or in R. J. Young
& P. A. Lovell, Introduction to Polymers, (Chapman & Hall
1991), which are incorporated by reference herein.
Discussion of General Embodiments
[0096] From a pure optical standpoint, the depth of focus (DOF) for
an optical system (e.g. the eye) is simply defined as the maximum
movement away from the ideal image plane, which may be made without
causing a serious deterioration of the image. According to the
Rayleigh limit, there will be no appreciable deterioration of the
image, i.e., no marked change from the Airy pattern, provided the
maximum phase difference between disturbances arriving at the
center of the pattern, does not exceed .pi./2. With reference to
FIG. 1, this is mathematically stated as:
.delta.l = .+-. .lamda. 8 n ' .times. sin 2 .times. U ' 2
##EQU00001##
[0097] where AP represents a spherical wave converging to the image
point B, .lamda. is the wavelength, n' is the refractive index in
the image space, U' is the slope of the refracted ray, and 61 is
the DOF. Therefore, an optical system such as the human eye will
have an inherent amount of depth of focus even for a perfectly
imaging system.
[0098] An additional property of optical systems that can be
exploited to further increase the depth of focus, and therefore
provide for both distance and near vision, is spherical aberration.
In simple terms, spherical aberration is defined as the variation
of focus with aperture. FIG. 2 graphically depicts a collimated
beam of light being refracted by a spherical biconvex lens. Notice
that the rays closest to the optical axis come to a focus close to
the paraxial focus position. As the ray height at the lens
increases, the position of the ray's intersection with the optical
axis moves farther and farther away from the paraxial focus. The
distance from the paraxial focus to the axial intersection of the
ray is called longitudinal spherical aberration. The image of a
point formed by a lens with spherical aberration is usually a
bright dot surrounded by a halo of light. The effect of spherical
aberration on an extended image is to soften the contrast of the
image and blur its details. However, it should be possible to
induce a specific spherical aberration that increases the depth of
focus such that the softening of the focus and the image contrast
is acceptable.
[0099] The presence of spherical aberration increases the depth of
focus in the eye. In combination with a residual refractive error
(defocus), an induced spherical aberration can be used to provide
patients with good contrast images both for distance and near
objects. The key issue is to determine the required values of both
4.sup.th order spherical aberration and defocus that provide good
near vision without deteriorating the image quality for distance
objects. An experimental approach that permits determination of the
optimum values of spherical aberration and defocus is an adaptive
optics visual simulator. (Fernandez et al., 2002). An example of
this type of instrument is shown in FIG. 3. This instrument
consists of a wavefront sensor (Shack-Hartmann wavefront sensor), a
wavefront corrector (Liquid Crystal on Silicon (LCOS)), and an
additional optical path to present letters, e.g., a tumbling E, to
the subjects under test. The visual acuity of several subjects was
measured using a similar setup as that shown in FIG. 3. The visual
acuity of the subjects was measured through simulations that
consisted of a number of different combinations of residual defocus
and spherical aberration measurements for letter objects placed at
distances from 30 cm to distance emmetropia. The results of these
simulations indicate that the optimum values of negative spherical
aberration and defocus to maintain good vision between 40 cm and
distance emmetropia are -0.125 .mu.m of 4.sup.th order spherical
aberration in combination with -1.0 D of defocus.
[0100] The spherical IOL of the present invention is capable of
post-fabrication alteration of optical properties. The lens is
self-contained and does not require the addition or removal of
materials to change the optical properties. Instead, the optical
properties of the lens are altered by exposing a portion or
portions of the lens to an external stimulus which induces
polymerization of a MC within the lens. The polymerization of the
MC, in turn, causes the change in optical properties.
[0101] In some examples, the optical element of the invention has
dispersed within it a MC. The MC is capable of diffusion within the
lens; can be readily polymerized by exposure to a suitable external
stimulus; and is compatible with the materials used to make the
first polymer matrix of the lens.
[0102] The method for providing an aspheric lens begins with the
formation of the first polymer matrix. After the first polymer
matrix is formed, the second polymer matrix is formed by exposing
the first polymer matrix, which further comprises the MC, to an
external stimulus. During this second polymerization, several
changes occur within the optical element. The first change is the
formation of a second polymer matrix comprising polymerized MC. The
formation of the second polymer network can cause changes in the
optical properties of the element, namely the refractive index. In
addition, when the MC polymerizes, a difference in the chemical
potential between the polymerized and unpolymerized region is
induced. This in turn causes the unpolymerized MC to diffuse within
the element, which reestablishes thermodynamic equilibrium of the
optical element. If the optical element possesses sufficient
elasticity, this migration of MC can cause swelling of the element
in the area exposed to the stimulus. This, in turn, changes the
shape of the element, causing changes in the optical properties.
Whether the radius of curvature of the element and/or the
refractive index of the element change depends upon (1) the nature
of the optical element, (2) the MC incorporated into the element,
(3) the duration that the element is exposed to the stimulus, and
(4) the spatial intensity profile of the stimulus. A schematic
depicting the process for increasing the power of the lens is
displayed in FIG. 4.
[0103] The optical element is typically made of a first polymer
matrix. Illustrative examples of a suitable first polymer matrix
include: (1) polyacrylates such as polyalkyl acrylates and
polyhydroxyalkyl acrylates; (2) polymethacrylates such as
polymethyl methacrylate ("PMMA"), polyhydroxyethyl methacrylate
("PHEMA"), and polyhydroxypropyl methacrylate ("HPMA"); (3)
polyvinyls such as polystyrene and polyvinylpyrrolidone ("PNVP");
(4) polysiloxanes such as polydimethylsiloxane; polyphosphazenes,
and/or (5) copolymers thereof. U.S. Pat. No. 4,260,725 and patents
and references cited therein (which are all incorporated herein by
reference) provide more specific examples of suitable polymers that
may be used to form the first polymer matrix.
[0104] In preferred embodiments, where flexibility is desired, the
first polymer matrix generally possesses a relatively low glass
transition temperature ("T.sub.g") such that the resulting IOL
tends to exhibit fluid-like and/or elastomeric behavior, and is
typically formed by cross-linking one or more polymeric starting
materials wherein each polymeric starting material includes at
least one cross-linkable group. In the case of an intraocular lens,
the T.sub.g should be less than 25.degree. C. This allows the lens
to be folded, facilitating implantation.
[0105] The crosslinking reaction of the polymeric starting material
is accomplished via a hydrosilylation reaction. The general scheme
for the hydrosilylation reaction is shown below.
##STR00009##
[0106] During this crosslinking step, a high molecular weight long
vinyl-capped silicone polymer and multi-functional vinyl-capped
silicone resin are crosslinked using multifunctional hydrosilane
crosslinkers. This crosslinking step forms the first polymer matrix
in the presence of MC and photoinitiator.
[0107] In some embodiments, the high molecular weight, long
vinyl-capped silicone polymer has the following formula.
##STR00010##
[0108] In some examples, m represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0109] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0110] In some embodiments, multi-functional vinyl-capped silicone
resin has the following formula.
##STR00011##
[0111] In some examples, x represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, x represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0112] In some examples, y represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, y represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0113] In some embodiments, multi-functional hydrosilane
crosslinker has the following formula.
##STR00012##
[0114] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0115] Illustrative examples of suitable cross-linkable groups
include but are not limited to vinyl, hydride, acetoxy, alkoxy,
amino, anhydride, aryloxy, carboxy, enoxy, epoxy, halide, isocyano,
olefinic, and oxine. In more preferred embodiments, the polymeric
starting material includes terminal monomers (also referred to as
endcaps) that are either the same or different from the one or more
monomers that comprise the polymeric starting material but include
at least one cross-linkable group. In other words, the terminal
monomers begin and end the polymeric starting material and include
at least one cross-linkable group as part of its structure.
Although it is not necessary for the practice of the present
invention, the mechanism for cross-linking the polymeric starting
material preferably is different than the mechanism for the
stimulus-induced polymerization of the components that comprise the
refraction modulating composition. For example, if the refraction
modulating composition is polymerized by photoinduced
polymerization, then it is preferred that the polymeric starting
materials have cross-linkable groups that are polymerized by any
mechanism other than photoinduced polymerization.
[0116] An especially preferred class of polymeric starting
materials for the formation of the first polymer matrix is
polysiloxanes (also known as "silicones") endcapped with a terminal
monomer which includes a cross-linkable group selected from the
group consisting of vinyl, acetoxy, amino, alkoxy, halide, hydroxy,
and mercapto. Because silicone IOLs tend to be flexible and
foldable, generally smaller incisions may be used during the IOL
implantation procedure. An example of an especially preferred
polymeric starting materials are vinyl endcapped dimethylsiloxane
diphenylsiloxane copolymer, silicone resin, and silicone hydride
crosslinker that are crosslinked via an addition polymerization by
platinum catalyst to form the silicone matrix (see the above
reaction scheme). Other such examples may be found in U.S. Pat.
Nos. 5,236,970; 5,376,694; 5,278,258; 5,444,106; and, others
similar to the described formulations. U.S. Pat. Nos. 5,236,970;
5,376,694; 5,278,258; and 5,444,106 are incorporated herein by
reference in their entirety.
[0117] The MC that is used in fabricating IOLs is as described
above except that it has the additional requirement of
biocompatibility. The MC is capable of stimulus-induced
polymerization and may be a single component or multiple components
so long as: (1) it is compatible with the formation of the first
polymer matrix; (2) it remains capable of stimulus-induced
polymerization after the formation of the first polymer matrix; and
(3) it is freely diffusible within the first polymer matrix. In
general, the same type of monomers that are used to form the first
polymer matrix may be used as components of the refraction
modulating composition. However, because of the requirement that
the MC macromer must be diffusible within the first polymer matrix,
the MC macromers generally tend to be smaller (i.e., have lower
molecular weights) than the starting polymeric materials used to
form the first polymer matrix. In addition to the one or more
monomers, the MC may include other components such as initiators
and sensitizers that facilitate the formation of the second polymer
network.
[0118] In preferred embodiments, the stimulus-induced
polymerization is photopolymerization. In other words, the one or
more monomers or macromers that comprise the refraction modulating
composition each preferably includes at least one group that is
capable of photopolymerization. Illustrative examples of such
photopolymerizable groups include but are not limited to acrylate,
allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. In more
preferred embodiments, the refraction modulating composition
includes a photoinitiator (any compound used to generate free
radicals) either alone or in the presence of a sensitizer. Examples
of suitable photoinitiators include acetophenones (e.g.,
substituted haloacetophenones, and diethoxyacetophenone);
2,4-dichloromethyl-1,3,5-trazines; benzoin methyl ether; and
o-benzoyl oximino ketone. Examples of suitable sensitizers include
p-(dialkyiamino)aryl aldehyde; N-alkylindolylidene; and
bis[p-(dialkylamino)benzylidene] ketone.
[0119] Because of the preference for flexible and foldable IOLs, an
especially preferred class of MC monomers is polysiloxanes
endcapped with a terminal siloxane moiety that includes a
photopolymerizable group. Non-limiting examples of a suitable
photopolymerizable group include, but are not limited to acrylate,
allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. An
illustrative representation of such a monomer is:
X--Y--X.sup.1
[0120] wherein Y is a siloxane which may be a monomer, a
homopolymer or a copolymer formed from any number of siloxane
units, and X and X.sup.1 may be the same or different and are each
independently a terminal siloxane moiety that includes a
photopolymerizable group. Non-limiting examples of a suitable
photopolymerizable group include, but are not limited to acrylate,
allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. An
illustrative example of Y includes:
##STR00013##
[0121] wherein m and n are independently each an integer; and,
R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently each
hydrogen, alkyl (substituted, primary, secondary, tertiary,
cycloalkyl), aryl, or heteroaryl. In preferred embodiments,
R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently
C.sub.1-C.sub.10 alkyl or phenyl. Because MC monomers with a
relatively high aryl content have been found to produce larger
changes in the refractive index of the inventive lens, it is
generally preferred that at least one of R.sup.1, R.sup.2, R.sup.3,
and R.sup.4 is an aryl, particularly phenyl. In more preferred
embodiments, R.sup.1, R.sup.2, and R.sup.3 are the same and are
methyl, ethyl or propyl with the proviso that R.sup.4 is
phenyl.
[0122] In some examples, m represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0123] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0124] Illustrative examples of X and X.sup.1 (or X.sup.1 and X
depending on how the MC polymer is depicted) are:
##STR00014##
[0125] respectively wherein: R.sup.5 and R.sup.6 are independently
each hydrogen, alkyl, aryl, or heteroaryl; and Z is a
photopolymerizable group.
[0126] In preferred embodiments R.sup.5 and R.sup.6 are
independently each C.sub.1-C.sub.10 alkyl or phenyl and Z is a
photopolymerizable group that includes a moiety selected from the
group consisting of acrylate, allyloxy, cinnamoyl, methacrylate,
stibenyl, and vinyl. In more preferred embodiments, R.sup.5 and
R.sup.6 are methyl, ethyl, or propyl and Z is a photopolymerizable
group that includes an acrylate or methacrylate moiety.
[0127] In some embodiments, a MC macromer has the following
formula:
##STR00015##
[0128] wherein X and X.sup.1 are the same as defined above, and
wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are the same as
defined above. In some examples, m represents an integer having a
value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500;
1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1
and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1
and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1
and 500 or any range found within any of the aforementioned ranges.
In some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0129] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0130] In general, a suitable modifying composition consists of a
lower molecular weight polydimethyl-siloxane macromer containing
polymerizable methacrylate functional end groups and a bezoin
photoinitiator. In some embodiments, a suitable modifying
composition has the following formula.
##STR00016##
[0131] The above structure is a polydimethyl siloxane end-capped
with photopolymerizable methacrylate functional groups. In some
examples, x represents an integer having a value between 1 and
10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and
7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and
5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and
2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any
range found within any of the aforementioned ranges. In some
examples, x represents an integer having an average value between 1
and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1
and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1
and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1
and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any
range found within any of the aforementioned ranges.
[0132] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0133] In some embodiments, a suitable modifying composition has
the following formula.
##STR00017##
[0134] The above modifying composition has a structure comprising a
polydimethyl siloxane end-capped with benzoin photoinitiator. In
some examples, x represents an integer having a value between 1 and
10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and
7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and
5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and
2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any
range found within any of the aforementioned ranges. In some
examples, x represents an integer having an average value between 1
and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1
and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1
and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1
and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any
range found within any of the aforementioned ranges.
[0135] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0136] Additional illustrative examples of such MC monomers include
dimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyl
dimethylsilane group (see below);
##STR00018##
[0137] In some examples, m represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0138] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0139] Another illustrative examples of such MC monomers includes
dimethylsiloxane-methylphenylsiloxane copolymer endcapped with a
methacryloxypropyl dimethylsilane group (see below);
##STR00019##
[0140] In some examples, m represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0141] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0142] A preferred modifying composition is the dimethylsiloxane
macromer endcapped with a methacryloxypropyldimethylsilane group
(see below).
##STR00020##
[0143] In some examples, x represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, x represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0144] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0145] Although any suitable method may be used, a ring-opening
reaction of one or more cyclic siloxanes in the presence of triflic
acid has been found to be a particularly efficient method of making
a class of MC monomers. Briefly, the method comprises contacting a
cyclic siloxane with a compound of the formula:
##STR00021##
[0146] in the presence of triflic acid wherein R.sup.5 and R.sup.6
are independently each hydrogen, alkyl, aryl, or heteroaryl; and Z
is a photopolymerizable group. The cyclic siloxane may be a cyclic
siloxane monomer, homopolymer, or copolymer. Alternatively, more
than one cyclic siloxane may be used. For example, a cyclic
dimethylsiloxane tetrameter and a cyclic methyl-phenylsiloxane
trimer are contacted with
bis-methacryloxypropyltetramethyldisiloxane in the presence of
triflic acid to form a dimethyl-siloxane methyl-phenylsiloxane
copolymer that is endcapped with a
methacryloxylpropyl-dimethylsilane group, an especially preferred
MC monomer, such as the MC monomer shown below.
##STR00022##
[0147] In some examples, x represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, x represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0148] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0149] In addition to the silicone-based MCs described above,
acrylate-based MC can also be used in the practice of the
invention. The acrylate-based macromers of the invention have the
general structure wherein X and X.sup.1 may be the same or
different and/or are each independently a terminal siloxane moiety
that includes a photopolymerizable group. Non-limiting examples of
a suitable photopolymerizable group include, but are not limited to
acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and
vinyl
X-A.sub.n-Q-A.sub.n-X.sup.1
or
X-A.sub.n-A.sup.1.sub.m-Q-A.sup.1.sub.m-A.sub.n-X.sup.1
[0150] wherein Q is an acrylate moiety capable of acting as an
initiator for Atom Transfer Radical Polymerization ("ATRP"), A and
A.sup.1 have the general structure:
##STR00023##
[0151] wherein R.sup.1 is selected from the group comprising
alkyls, halogenated alkyls, aryls and halogenated aryls and X and
X.sup.1 are groups containing photopolymerizable moieties and m and
n are integers. In some examples, m represents an integer having a
value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500;
1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1
and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1
and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1
and 500 or any range found within any of the aforementioned ranges.
In some examples, m represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0152] In some examples, n represents an integer having a value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges. In
some examples, n represents an integer having an average value
between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and
8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and
5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and
3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and
500 or any range found within any of the aforementioned ranges.
[0153] In one embodiment the acrylate based MC macromer has the
formula:
##STR00024##
[0154] wherein R.sup.2 is alkyl or halogenated alkyl; R.sup.3 is
alkyl, halogenated alkyl, aryl or halogenated aryls; R.sup.4 is
alkyl, halogenated alkyl, aryl or halogenated aryl; and, with the
proviso that R.sup.3 and R.sup.4 are different. In some
embodiments, the value of n is between 1 and 200; 1 and 190; 1 and
180; 1 and 170; 1 and 160; 1 and 150; 1 and 140; 1 and 130; 1 and
120; 1 and 110; 1 and 100; 1 and 90; 1 and 80; 1 and 70; 1 and 60;
1 and 50; 1 and 40; 1 and 30; 1 and 20; 1 and 10; or any range in
between. For example, when the value of n is between 1 and 200,
this also contemplates a value of n between 17 and 24. In some
embodiments the value of m is between 1 and 200; 1 and 190; 1 and
180; 1 and 170; 1 and 160; 1 and 150; 1 and 140; 1 and 130; 1 and
120; 1 and 110; 1 and 100; 1 and 90; 1 and 80; 1 and 70; 1 and 60;
1 and 50; 1 and 40; 1 and 30; 1 and 20; 1 and 10; or any range in
between. For example, when the value of m is between 1 and 200,
this also contemplates a value of m between 17 and 24.
[0155] After the optical element is formed, it is then positioned
in the area where the optical properties are to be modified. For an
intraocular lens, this means implantation into the eye using known
procedures. Once the element is in place and is allowed to adjust
to its environment, it is then possible to modify the optical
properties of the element through exposure to an external
stimulus.
[0156] The nature of the external stimulus can vary but it must be
capable of reducing polymerization of the MC without adversely
affecting the properties of the optical element. Typical external
stimuli that can be used in practice of the invention include heat
and light, with light preferred. In the case of intraocular lenses,
ultraviolet or infrared radiation is preferred with ultraviolet
light most preferred.
[0157] When the element is exposed to the external stimulus, the MC
polymerization forms a second polymer matrix, interspersed within
the first polymer matrix. When the polymerization is localized or
when only a portion of the MC is polymerized, there is a difference
in the chemical potential between the reacted and unreacted regions
of the lens. The MC then migrates within the element to reestablish
the thermodynamic equilibrium within the optical element.
[0158] The formation of the second polymer matrix and the
re-distribution of the MC can each affect the optical properties of
the element. For example, the formation of the second polymer
matrix can cause changes in the refractive index of the element.
The migration of the modifying compound can alter the overall shape
of the element, further affecting the optical properties by
changing the radii of curvatures of the optical element.
[0159] It is possible to expose the optical element to a spatially
defined irradiance profile to create a lens with different optical
properties. In one embodiment, it is possible to create an
intraocular lens that can be converted into an aspheric lens after
implantation. This is accomplished by exposing the lens to a
mathematically defined spatial irradiance profile. A.sub.n example
of the type of profiles that can be used to induce asphericity in
the lens are of the form
Asph(.rho.)=A.rho..sup.4-B.rho..sup.2+1 (1)
[0160] where A and B are coefficients and .rho. is a radial
coordinate. A normalized plot of this function, where A=B=4, is
displayed in FIG. 5.
[0161] Another approach is to linearly combine weighted amounts of
the profile (Asph) displayed in equation 1 with spatial irradiance
profiles that are currently used to correct for spherical
refractive errors and spherocylindrical refractive errors as well
as with Power Neutral Profiles, i.e., profiles that neither add or
subtract refractive power from the LAL. This approach has the dual
benefits of correcting the lower aberrations, e.g. sphere and
cylinder, along with imparting the requisite amount of induced
asphericity to provide increased depth of focus. This can be
described mathematically as follows:
Profile(.rho.)=SCN(.rho.)+.beta.Asph(.rho.) (2)
[0162] where SCN(.rho.) refers to either a spherical,
spherocylindrical or power neutral spatial irradiance profile,
Asph(.rho.) is the same as in equation 1, and .beta. is a weighting
factor that can range from 0 to 1. As an example of this approach,
consider the cross-sectional profiles shown in FIG. 6. These plots
were generated by combining weighted amounts of the profile
represented by equation 1 with a power neutral profile.
[0163] By way of a reaction sequence, the following example shows
how the formation of the second polymer matrix and the
re-distribution of the MC is accomplished. In the example provided
below, the MC having the formula:
##STR00025##
[0164] is exposed to UV light, thereby creating a radical species.
This process is represented schematically in the reaction scheme
below.
##STR00026##
[0165] After exposing the MC to UV light, the resulting radical
species are free to react with the first polymer matrix. In the
example, below the first polymer matrix was formed using a polymer
having the following structure:
##STR00027##
[0166] The radical species generated by exposing the MC to UV light
then reacts with the first polymer matrix according to the reaction
scheme below:
##STR00028##
[0167] The reaction scheme for photopolymerization of
photo-reactive MC in the presence of the first polymer lens matrix
is the same for the adjustment and lock-in procedures. The
difference between the adjustment procedure and lock-in procedure
is the spatial irradiance profiles applied to each procedure.
EXAMPLES
[0168] The following examples are included to demonstrate preferred
embodiments of the invention. It should be appreciated by those of
skill in the art that the techniques disclosed in the examples
which follow represent techniques discovered by the inventor to
function well in the practice of the invention, and thus can be
considered to constitute preferred modes for its practice.
[0169] However, those of skill in the art should, in light of the
present disclosure, appreciate that many changes can be made in the
specific embodiments which are disclosed and still obtain a like or
similar result without departing from the spirit and scope of the
invention.
Example 1
[0170] A series of light adjustable lenses containing a
silicone-based MC were prepared using standard molding techniques
known to those skilled in the art. The lens had a first polymer
matrix prepared from a silicone hydride crosslinked vinyl endcapped
diphenylsiloxane dimethylsiloxane. The first polymer matrix
comprised about 70 weight % of the lens. The lens also comprised
about 30 weight % of a MC (methacrylate endcapped
polydimethylsiloxane), 1 weight % (based on MC) of a photoinitiator
(benzoin-tetrasiloxane-benzoin), and 0.04 weight % (based on MC) UV
absorber. The lenses had an initial nominal power of +20.0
diopters. Twelve groups, of four LALs each, were exposed to a
spatial irradiance profile defined by Equation 2 with beta values
ranging from 0.05 to 0.57. Table 1 summarizes the specific spatial
irradiance profile, average irradiance, and time applied to each of
the LAL groups. At 48 hours post irradiation, the wavefronts of
each of the lenses was measured. The measured 4.sup.th (Z12) and
6.sup.th (Z24) order spherical aberration values for each of the 12
irradiation groups were averaged together and plotted as a function
of increasing .beta. value as show in FIG. 7.
TABLE-US-00001 TABLE 1 Summary of treatment conditions and induced
spherical aberration for those lenses that did not receive a prior
adjustment. The measurement aperture was 4 mm for all spherica
aberration measurements. Applied .DELTA.4th .DELTA. 6th Duration
Power Bm Size Order SA Order SA Lens ID Profile (sec) (mW) (mm)
.DELTA. Z12 (.mu.m) .DELTA. Z24 (.mu.m) 6699 In-vitro PN Profile +
Beta = 0.05 90 4.130 5.30 0.194 0.016 6701 In-vitro PN Profile +
Beta = 0.05 90 4.130 5.30 0.115 0.050 6706 In-vitro PN Profile +
Beta = 0.05 90 4.130 5.30 0.003 0.054 6708 In-vitro PN Profile +
Beta = 0.05 90 4.130 5.30 0.029 0.053 Average 0.085 0.043 St. Dev
0.087 0.018 189-26 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30
-0.019 0.017 189-29 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30
-0.024 0.017 189-31 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30
-0.020 0.016 189-33 In-vitro PN Profile + Beta = 0.10 90 3.820 5.30
-0.036 0.013 Average -0.025 0.016 St. Dev 0.008 0.002 189-27
In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 -0.056 0.013 189-30
In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 -0.055 0.013 189-32
In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 -0.054 0.012 189-34
In-vitro PN Profile + Beta = 0.15 90 3.670 5.30 -0.060 0.010
Average -0.056 0.012 St. Dev 0.003 0.001 189-35 In-vitro PN Profile
+ Beta = 0.20 90 3.510 5.30 -0.088 0.018 189-38 In-vitro PN Profile
+ Beta = 0.20 90 3.510 5.30 -0.088 0.013 189-40 In-vitro PN Profile
+ Beta = 0.20 90 3.510 5.30 -0.083 0.018 189-44 In-vitro PN Profile
+ Beta = 0.20 90 3.510 5.30 -0.081 0.013 Average -0.085 0.015 St.
Dev 0.003 0.003 189-37 In-vitro PN Profile + Beta = 0.25 90 3.360
5.30 -0.107 0.013 189-39 In-vitro PN Profile + Beta = 0.25 90 3.360
5.30 -0.111 0.006 189-41 In-vitro PN Profile + Beta = 0.25 90 3.360
5.30 -0.106 0.009 189-45 In-vitro PN Profile + Beta = 0.25 90 3.360
5.30 -0.130 0.006 Average -0.113 0.009 St. Dev 0.011 0.003 185-3-2
In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 -0.151 0.010
185-3-15 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30 -0.156
0.008 188-2-18 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30
-0.163 0.012 189-47 In-vitro PN Profile + Beta = 0.30 90 3.210 5.30
-0.148 0.007 Average -0.155 0.009 St. Dev 0.007 0.002 185-3-11
In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 -0.193 0.005
188-2-16 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 -0.194
0.003 189-46 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 -0.192
0.002 189-48 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30 -0.182
0.002 Average -0.190 0.003 St. Dev 0.006 0.002 6700 In-vitro PN
Profile + Beta = 0.40 90 2.900 5.30 -0.240 0.013 6704 In-vitro PN
Profile + Beta = 0.40 90 2.900 5.30 -0.241 0.011 6707 In-vitro PN
Profile + Beta = 0.40 90 2.900 5.30 -0.222 0.011 6709 In-vitro PN
Profile + Beta = 0.40 90 2.900 5.30 -0.224 0.017 Average -0.232
0.013 St. Dev 0.010 0.003 6710 In-vitro PN Profile + Beta = 0.45 90
2.750 5.30 -0.277 0.004 6712 In-vitro PN Profile + Beta = 0.45 90
2.750 5.30 -0.284 0.003 6715 In-vitro PN Profile + Beta = 0.45 90
2.750 5.30 -0.274 0.006 6717 In-vitro PN Profile + Beta = 0.45 90
2.750 5.30 -0.266 -0.002 average -0.275 0.003 St. Dev 0.007 0.003
6713 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 -0.303 0.001
6716 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 -0.322 -0.002
6718 In-vitro PN Profile + Beta = 0.50 90 2.600 5.30 -0.318 -0.009
Average -0.314 -0.003 St. Dev 0.010 0.005 6719 In-vitro PN Profile
+ Beta = 0.55 90 2.440 5.30 -0.356 -0.009 6723 In-vitro PN Profile
+ Beta = 0.55 90 2.440 5.30 -0.347 -0.016 6727 In-vitro PN Profile
+ Beta = 0.55 90 2.440 5.30 -0.350 -0.011 6729 In-vitro PN Profile
+ Beta = 0.55 90 2.440 5.30 -0.350 -0.021 Average -0.351 -0.014 St.
Dev 0.004 0.006 6721 In-vitro PN Profile + Beta = 0.57 90 2.380
5.30 -0.368 -0.015 6725 In-vitro PN Profile + Beta = 0.57 90 2.380
5.30 -0.350 -0.026 6728 In-vitro PN Profile + Beta = 0.57 90 2.380
5.30 -0.359 -0.019 6730 In-vitro PN Profile + Beta = 0.57 90 2.380
5.30 -0.385 -0.030 Average -0.366 -0.022 St. Dev 0.015 0.007
[0171] Inspection of the plot indicates several interesting
features. The first is the nearly linearly increase in induced 4th
order spherical aberration as a function of increasing .beta.
value. The second feature is the nearly complete absence of any
6.sup.th order spherical aberration induction, indicating that the
induced spherical aberration is essentially pure 4.sup.th order
spherical aberration. This is important because it has been shown
that the presence of 6.sup.th order spherical aberration will have
the affect of nulling out any induced depth of focus produced by
the induction of negative 4.sup.th order spherical aberration.
(Thibos et al., 2004) The third feature to note is the small
standard deviation in the average, induced 4.sup.th order spherical
aberration for a specific .beta. value. This fact indicates that it
is possible to adjust the amount of asphericity in the LAL by
targeted, discrete values, which will allow true customization of
patients' depth of focus. And finally, as written above, the
targeted amount of total ocular 4.sup.th order spherical aberration
for optimizing visual acuity between 40 cm and distance emmetropia
is -0.125 .mu.m. Inspection of the data in Table 2 and FIG. 7 and
assuming an average starting ocular spherical aberration at a 4 mm
aperture of +0.10 .mu.m, indicates that the profile with a beta
value of 0.40 would be ideal for inducing the requisite amount of
negative asphericity.
[0172] The above example involved irradiating LALs that had not
received a prior adjustment. However, there will be instances where
it is necessary to first adjust the spherical and/or
spherocylindrical power of the LAL before the aspheric adjustment.
The LAL is a closed thermodynamic system, i.e. we can't add or
remove particles, MC, from the lens. As a consequence, each
subsequent refractive adjustment consumes MC leaving less for
subsequent adjustments. In addition, upon polymerization of MC
during adjustment, the polymerized MC forms an interpenetrating
matrix with the host matrix polymer. This action has the effect of
increasing the stiffness of the lens. Because the refractive
change, i.e. spherical, spherocylindrical, aspheric, etc., of the
LAL is accomplished by a shape change, the amount of induced
asphericity after an initial adjustment should be reduced for same
treatment conditions as with the no prior adjustment cases
summarized in FIG. 7.
[0173] To investigate this, a series of LALs were initially given
either a myopic or hyperopic primary adjustment followed by an
aspheric treatment 48 hours post the initial, primary adjustment.
FIG. 8 displays both the 4.sup.th and 6.sup.th order spherical
aberration values for LALs that received either an initial
hyperopic or myopic adjustment followed by an aspheric treatment
with beta values ranging between 0.30 and 0.57. For comparison, the
LALs that received the aspheric treatment as a primary adjustment
are also plotted on the same graph.
[0174] Inspection and comparison of the data for the different
treatment conditions indicate several interesting trends. The first
overall theme is that, as expected, increasing the beta value,
which effectively increases the amount of aspheric character of the
treatment beam, has the effect of increasing the amount of induced
4.sup.th order asphericity in the LAL. This is true whether the LAL
initially received a primary adjustment or if the LAL has received
no prior adjustment. The second thing to note is that for a given
beta, mediated aspheric profile, the type of refractive adjustment
preceding the aspheric treatment directly impacts how much 4.sup.th
order asphericity is induced in the lens. For example, consider the
three different sets of LALs that were adjusted with the
.beta.=0.57 aspheric profile after a hyperopic adjustment, a myopic
adjustment, and no adjustment. Inspection of the graph indicates
that those lenses receiving no prior adjustment displayed the
largest amount of induced 4.sup.th order spherical aberration,
followed by the LALs that initially received a myopic adjustment,
with the LALs after a hyperopic adjustment showing the smallest
amount of induced asphericity. The reasons for this general trend
are twofold. The first, which was discussed above, is due to the
simple fact that the LALs that received no prior adjustment
obviously have more starting MC and the LAL matrix is not as stiff
as compared to the other two sets of LALs and thus, for the same
given aspheric dose, should show more 4.sup.th order asphericity
induction. The reasons why the LALs receiving an initial myopic
adjustment display greater amounts of induced 4.sup.th order
spherical aberration as compared to those LALs receiving a
hyperopic adjustment as their primary adjustment, even though the
magnitude of the refractive change (-1.0 D vs+1.0 D) is the same,
can be explained by the fact that the total energy underneath the
spatial irradiance profile for the given myopic adjustment is less
than that as compared to the hyperopic adjustment profile. Because
of this fact, more macromer will be consumed during the initial
hyperopic adjustment and a stronger, interpenetrating network will
be formed, thus preventing more aspheric induction. Another
important aspect of the data to note, is that regardless of prior
adjustment, the application of the aspheric treatment does not
induce any 6.sup.th order spherical aberration.
Example 2
[0175] To test the ability of the aspheric adjustment profiles to
induce enough asphericity to provide patients with increased depth
of focus, a series of subjects were implanted with the light
adjustable lens after routine cataract surgery, given a prior
treatment to correct for postoperative residual sphere and
cylinder, and then given an aspheric adjustment using the corneal
compensated versions of the profiles described in Example 1. FIG. 9
and Table 2 summarize the monocular visual acuity data for a series
of 32 eyes adjusted with aspheric profiles possessing a beta value
between 0.40 and 0.57. For comparison, the average uncorrected
visual acuity values for 12 eyes implanted with a LAL and adjusted
for distance emmetropia only, are displayed as well. All of the
LALs received some type of primary adjustment before the
application of the aspheric profile.
[0176] Inspection of the graph in FIG. 9 indicates several
important features. The first is that, on average, from 40 cm to
distance emmetropia, the patients adjusted with an aspheric
treatment profile possessed uncorrected visual acuities between
20/20 and 20/32. In fact, as summarized in Table 2, 75% of the eyes
treated with the aspheric profile treatment regimen, possess an
uncorrected visual acuity of 20/32 or better from 40 cm to distance
emmetropia. In contrast, inspection of the results for those eyes
receiving treatment to correct for residual spherical and
spherocylindrical refractive errors, only, show that while the
distance, uncorrected visual acuity results are better than the
aspheric cases (83%>20/20 and 100>20/25 or better), these
eyes, as expected, have essentially no near vision capability, i.e.
80 (1/12) see at least 20/32 at 40 cm. Therefore, this data
indicates that the application of the aspheric profiles to
implanted LALs has the ability to increase the depth of focus of a
patients' eye.
TABLE-US-00002 TABLE 2 Monocular visual acuity (VA) results for
those eyes receiving an aspheric treatment (n = 32). VA FAR 60 cm
40 cm Far BCVA .gtoreq.20/20 9/32 (28 %) 17/32 (53%) 2/32 (6%)
21/32 (65%) .gtoreq.20/25 23/32 (72 %) 27/32 (84%) 11/32 (35%)
31/32 (97%) .gtoreq.20/32 28/32 (88 %) 32/32 (100%) 24/32 (75%)
32/32 (100%) .gtoreq.20/40 32/32 (100%) 32/32 (100%) 31/32 (97%)
32/32 (100%) .gtoreq.20/60 32/32 (100%) 32/32 (100%) 32/32 (100%)
32/32 (100%)
TABLE-US-00003 TABLE 3 Monocular visual acuity (VA) results for
those LAL eyes adjusted for distance visual acuity only (n = 12).
VA FAR 60 cm 40 cm Far BCVA .gtoreq.20/20 10/12 (83%) 1/12 (8%)
0/12 (0%) 12/12 (100%) .gtoreq.20/25 12/12 (100%) 3/12 (25%) 0/12
(0%) 12/12 (100%) .gtoreq.20/32 12/12 (100%) 8/12 (67%) 1/12 (8%)
12/12 (100%) .gtoreq.20/40 12/12 (100%) 12/12 (100%) 7/12 (58%)
12/12 (100%) .gtoreq.20/60 12/12 (100%) 12/12 (100%) 12/12 (100%)
12/12 (100%)
[0177] As indicated in FIG. 9, the total measured 4.sup.th order
spherical aberration over a 4 mm pupil in the 32 eyes ranged from
-0.04 .mu.m to -0.23 .mu.m. As stated above, theoretical
considerations indicate that the ideal amount of final 4.sup.th
order spherical aberration to provide optimal visual acuity between
40 cm and distance emmetropia is -0.125 .mu.m. To consider the
impact of this range of induced negative asphericity on the final
visual acuities at different object distances, FIG. 10 segregates
the 32 eyes into two groups: High Spherical Aberration (-0.10 .mu.m
to -0.23 m) and Low Spherical Aberration (-0.04 .mu.m to -0.10
.mu.m). As expected, those eyes with higher amounts of induced
negative spherical aberration, on average, show better visual
acuities at 40 cm (78% 7/9 patients .gtoreq.20/25 or J1) then those
with lower spherical aberration (22, 5/23 patients .gtoreq.20/25 or
J) with a slight decrease in their distance visual acuities (56% vs
78% at 20/25). However, inspection of the VA acuity curves from 40
cm to distance emmetropia in FIG. 10, indicate that, on average,
the curve is quite flat and the majority of the eyes possess visual
acuities of 20/25 or better. Comparison again with the 12 eyes
adjusted for distance emmetropia only, indicates that from 40 cm to
distance emmetropia, the eyes that received some type of aspheric
induction achieve much greater range of vision, i.e. increased
depth of focus.
TABLE-US-00004 TABLE 4 Monocular visual acuity (VA) results for
those eyes with low amounts of final 4.sup.th order spherical
aberration, -0.04 to -0.10 .mu.m (n = 23). VA FAR 60 cm 40 cm Far
BCVA .gtoreq.20/20 (J1+) 7/23 (30%) 12/23 (8%) 0/23 (0%) 15/23
(65%) .gtoreq.20/25 (J1) 15/23 (74%) 19/23 (83%) 5/23 (22%) 22/23
(96%) .gtoreq.20/32 (J2) 20/23 (100%) 23/23 (100%) 15/23 (65%)
12/12 (100%) .gtoreq.20/40 (J3) 23/23 (100%) 23/23 (100%) 23/23
(100%) 12/12 (100%) .gtoreq.20/60 23/23 (100%) 23/23 (100%) 23/23
(100%) 12/12 (100%)
TABLE-US-00005 TABLE 5 Monocular visual acuity (VA) results for
those eyes with high amounts of final 4th orders pherical
aberration, -0.11 to -0.23 .mu.m (n = 9). VA FAR 60 cm 40 cm Far
BCVA .gtoreq.20/20 (J1+) 2/9 (22%) 4/9 (8%) 2/9 (22%) 6/9 (67%)
.gtoreq.20/25 (J1) 5/9 (56%) 7/9 (78%) 7/9 (78%) 8/9 (89%)
.gtoreq.20/32 (J2) 8/9 (89%) 8/9 (89%) 9/9 (100%) 9/9 (100%)
.gtoreq.20/40 (J3) 9/9 (100%) 9/9 (100%) 9/9 (100%) 9/9 (100%)
.gtoreq.20/60 9/9 (100%) 9/9 (100%) 9/9 (100%) 9/9 (100%)
[0178] The above discussion considered the monocular visual
acuities of the treated eyes, only. However, one approach that will
optimize post LAL implantation patients' vision at all distances is
to correct one of the patients' eyes (usually the dominant eye) to
distance emmetropia and then to adjust the other eye of the patient
first to distance emmetropia followed by application of the
aspheric treatment. As an example of this procedure, consider the
data displayed in FIG. 11 and Table 6, which displays both the
monocular and binocular visual acuities for a series of patients
(n=10) that had a low (-0.04 .mu.m to -0.10 .mu.m) amount of
spherical aberration induced in one eye and the other eye was
implanted with a LAL and adjusted for distance emmetropia. For the
distance dominant eye, the final refraction varied between plano
and -0.50 D. Inspection of the monocular visual acuity results for
the two eyes displays the same visual characteristics already
discussed; namely, the eye corrected for distance emmetropia
displays excellent distance visual acuity, but rather poor near
vision and the aspheric eyes display improved depth of focus at the
expense of some distance visual acuity. However, the binocular
visual acuity data indicates that combining the two eyes provide
outstanding visual acuities from 40 cm to distance emmetropia. In
fact, 100% of the patients possessed a visual acuity of 20/25 or
better from 40 cm to distance emmetropia.
TABLE-US-00006 TABLE 6 Binocular visual acuity (VA) results for
those eyes with low amounts of final 4th order spherical
aberration, -0.04 to -0.10 mm in their non-dominant eye and with
their other eye adjusted for distance emmetropia. The refraction in
the dominant eye ranged from +0.25 D to -0.25 D (n = 10). VA FAR 60
cm 40 cm 30 cm .gtoreq.20/20 (J1+) 6/10 (60%) 8/10 (80%) 1/10 (10%)
0/10 (0%) .gtoreq.20/25 (J1) 10/10 (100%) 10/10 (100%) 4/10 (40%)
0/10 (0%) .gtoreq.20/32 (J2) 10/10 (100%) 10/10 (100%) 10/10 (100%)
3/10 (30%) .gtoreq.20/40 (J3) 10/10 (100%) 10/10 (100%) 10/10
(100%) 8/10 (80%) .gtoreq.20/60 10/10 (100%) 10/10 (100%) 10/10
(100%) 10/10 (100%)
[0179] Combining this binocular approach with those eyes having
high amounts of induced asphericity (-0.11 .mu.m to -0.23 .mu.m),
indicates that 100% (4/4) of the patients possessed an uncorrected
visual of 20/25 or better from 40 cm to distance emmetropia.
TABLE-US-00007 TABLE 7 Binocular visual acuity (VA) results for
those eyes with high amounts of final 4th order spherical
aberration, -0.11 to -0.23 .mu.m in their non-dominant eye and with
their other eye adjusted for distance emmetropia. The refraction in
the dominant eye ranged from +0.25 D to -0.25 D (n = 4). VA FAR 60
cm 40 cm 30 cm .gtoreq.20/20 (J1+) 4/4 (100%) 3/4 (75%) 1/10 (10%)
0/4 (0%) .gtoreq.20/25 (J1) 4/4 (100%) 4/4 (100%) 4/4 (100%) 1/4
(25%) .gtoreq.20/32 (J2) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4
(100%) .gtoreq.20/40 (J3) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4
(100%) .gtoreq.20/60 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4
(100%)
Example 3
[0180] General examples disclosed herein include an optical element
composed of matrix polymer and a modulating composition (MC) that
can be polymerized by an external stimulus (e.g. heat, light, etc)
to control the amount of induced asphericity.
[0181] In each of the aforementioned examples, the lens may include
an optical element that is a lens. In additional examples, the
optical element is an intraocular lens (IOL). Also, the amount of
induced asphericity is controlled by the application of a specific
spatial irradiance profile. In some examples, the amount of induced
asphericity is induced monocularly to induce extended depth of
focus.
[0182] In particular examples, the amount of induced asphericity is
tailored to provide intermediate vision (60-80 cm) or near vision
(30-40 cm). In specific embodiments, the amount of induced
asphericity can be customized for specific individual values.
[0183] In certain embodiments, the amount of induced asphericity is
induced binocularly to induce extended depth of focus. In
particular examples, one eye is tailored for intermediate (60-80
cm) vision by the induction of a particular value of asphericity
and the other eye is corrected for distance emmetropia. In
alternate embodiments, one eye is tailored for near vision (30-40
cm) by the induction of a particular value of asphericity and the
other eye is corrected for distance emmetropia. In further
embodiments, both eyes are tailored for intermediate (60-80 cm)
vision by the induction of particular value of asphericity. In yet
another embodiment, both eyes are tailored for near (30-40 cm)
vision by the induction of particular value of asphericity. In some
embodiments, one eye is tailored for intermediate (60-80 cm) vision
by the induction of negative asphericity and the other eye is
tailored for intermediate vision (60-80 cm) vision by the induction
of positive asphericity. In particular embodiments, one eye is
tailored for near vision (30-40 cm) vision by the induction of
negative asphericity and the other eye is tailored for near vision
(30-40 cm) vision by the induction of positive asphericity.
[0184] In some examples, the amount of induced asphericity of the
lens is tailored to compensate for the spherical aberration of the
cornea. In other examples, the amount of induced asphericity of
both lenses are tailored to compensate for the spherical aberration
of their respective corneas. In alternate examples, one lens is
adjusted to remove the spherical aberration of the entire eye and
the other lens is adjusted to induce asphercity for intermediate
vision (60-80 cm). In some examples, one lens is adjusted to remove
the spherical aberration of the entire eye and the other lens is
adjusted to induce asphercity for near vision (30-40 cm).
ADDITIONAL EMBODIMENTS
[0185] FIGS. 13A-B illustrate that, in order to address the above
described needs, embodiments of a Light Adjustable Lens (LAL) 100
can comprise a central region 110, centered on a central axis 112,
and a peripheral annulus 120, centered on an annulus axis 122 and
surrounding the central region 110, wherein the central axis 112 is
laterally shifted relative to the annulus axis 122 and the LAL axis
102.
[0186] FIGS. 13C-D show steps of a light adjustment procedure that
can be used to form the LAL 100 of FIGS. 13A-B. As shown in FIG.
13C, in typical embodiments the annulus axis 122 can be centered on
the LAL axis 102, or on the center of the dilated iris 5. (The
dilated/non-dilated status of the iris 5 is indicated in the
Figures.) At this stage, a first illumination 222 can be applied to
form the peripheral annulus 120, with a peripheral optical power
124, in the LAL 100, centered on the annulus axis 122. In some
embodiments, the peripheral annulus 120 can be pre-molded into the
LAL 100, instead of being formed after implantation. FIG. 13D shows
that next, the central axis 112 can be centered on a visual axis
132 of the eye, e.g., after the iris 5 returned to its non-dilated
state. Subsequently, a second illumination 242 can be applied to
form the central region 110, with a central optical power 114,
centered on this central axis 112, in order to optimize the optical
performance of the LAL 100. In this procedure, the central axis 112
often ends up shifted relative to the annulus axis 122 and the LAL
axis 102 for several reasons, including the following.
[0187] (1) First, during the surgical planning process, the doctor
may have not selected the optimal, most centered position for the
LAL 100.
[0188] (2) In other cases, the surgeon may have ended up implanting
the LAL 100 in a position shifted from the presurgical planned
position.
[0189] (3) In yet other cases, after the implantation, the LAL 100
may have shifted, or tilted away from its planned position, as
shown in FIGS. 13C-D.
[0190] (4) Finally, the first illumination 222 is often applied
with the iris 5 being dilated, to create the peripheral annulus 120
large enough to provide the desired optical performance even when
the iris 5 is in its most dilated state. In contrast, the
considerably smaller central region 110 is preferably formed with a
non-dilated iris 5, in order to center it on the visual axis 132
with high precision. This is so because the optical performance of
the small central region 110 deteriorates noticeably if it is not
aligned with the visual axis 132 well. And finally, since the iris
5 often does not dilate in a uniform, concentric manner, the center
of the relaxed, non-dilated iris 5 is often shifted relative to the
center of the dilated iris 5, and therefore, the central axis 112
is often shifted relative to the annulus axis 122.
[0191] The shift of the central axis 112 relative to the annulus
axis 122 will be sometimes abbreviated as axis shift 111. In
embodiments of the LAL 100, the axis shift 111 can be captured in
various ways. In absolute terms, the axis shift 111 can exceed 0.1
mm. In some embodiments, the axis shift 111 can exceed 0.2 mm. In
yet other embodiments, the axis shift 111 can exceed 0.5 mm. In
relative terms, the axis shift 111 can exceed 5% of the diameter of
the central region 110. In some embodiments, the axis shift 111 can
exceed 10% of the diameter of the central region 110. In yet
others, it can exceed 20% of the diameter of the central region
110. Finally, in manufacturing terms, the axis shift 111 can exceed
a manufacturing radius-tolerance of the LAL 100 by 20%. In other
embodiments, the axis shift 111 can exceed the manufacturing
radius-tolerance of the LAL 100 by 50%. This definition captures
that the axis shift 111 is not an accidental, or tolerance-induced
unintended shift of a pre-molded multifocal IOL, but an intended
shift, exceeding the manufacturing tolerance.
[0192] FIG. 13A illustrates the optical power of the LAL 100 as a
function of a radius r. The radius can be measured from a LAL axis
102. The central region 110 can have a position-dependent central
optical power 114, the peripheral annulus 120 can have a
position-dependent peripheral optical power 124. In embodiments, an
average of the central optical power 114 can be at least 0.5
diopter different from an average of the peripheral optical power
124. In some embodiments, the average of the central optical power
114 can be at least 1.0 diopter different from the average of the
peripheral optical power 124. Since the central axis 112 is shifted
relative to the annulus axis 122, which itself may be shifted
relative to the LAL axis 102, the central region 110 may be off a
center of the LAL 100, as shown.
[0193] The embodiments of the LAL 100 blend various aspects of the
EDOF and the CNA IOLs, since the LAL 100 has both a radially
varying optical power, thus giving rise to an EDOF, as well as a
central region 110, sometimes referred to as CNA region 110, and is
thus shares some of the attributes of a multifocal lens. For this
reason, embodiments of the LAL 100 will be interchangeably also
referenced as a blended LAL 100.
[0194] FIG. 13B illustrates the same regions of the LAL 100, from a
perspective along the LAL axis 102 of the LAL 100. In some
embodiments, the LAL axis 102, the central axis 112, and the
annulus axis 122 can all be different. In some typical embodiments,
the LAL axis 102 and the annulus axis 122 can at least
approximately coincide, and the central axis 112 can be shifted
relative to both the LAL axis 102 and the annulus axis 122, as
shown.
[0195] The position dependent optical power is typically induced by
illuminating the LAL 100 by applying a suitable illumination
pattern. The edge of the illumination pattern, a pattern edge 126
is also shown in FIGS. 13A-B, as a perimeter. Such blended LALs 100
can provide improvements for the above described medical problems
at least as follows.
[0196] (1) After the LAL 100 is implanted and settles in the
patient's eye, the central axis 112, and thus the central, or CNA
region 110 can be centered with the visual axis 132 of the eye with
the iris 5 being in a non-dilated state. It is recalled that the
visual axis 132 of the eye with the iris 5 being in its non-dilated
state often differs from either the geometrical LAL axis 102 of the
LAL 100, and from the visual axis of the eye with the iris 5 in its
dilated state. Therefore, a method that determines the eye visual
axis 132 only after the LAL 100 has shifted and settled in the eye,
and after the iris 5 returned to its approximately non-dilated
state, and only then applies the second illumination 242 centered
on the central axis 112 that is aligned with the eye visual axis
132, is an efficient method to center the CNA region 110 properly.
In the resulting blended LAL 100, the central axis 112 often ends
up laterally shifted relative to the annulus axis 122, as was
described in relation to FIGS. 13A-B. Thus, the described
embodiments of the blended LAL 100 are capable of overcoming the
above-mentioned de-centering challenge of pre-formed multifocal/CNA
IOLs, and avoid the shift-induced aberrations, such as coma.
[0197] (2) Since the near vision capability of these blended LALs
100 is primarily delivered by the CNA/central region 110, the
peripheral annulus 120 can be formed with a considerably smaller
radial variation of the peripheral optical power 124, which thus
extends the depth of focus only to a considerably smaller degree.
Therefore, the blurriness and aberrations, caused by the peripheral
annulus/EDOF region 120 of the blended LAL 100 is substantially
less than in an EDOF-only IOL/LAL.
[0198] (3) The same reduction of the radial variation of the
optical power in the blended LAL 100 causes the effective optical
power, experienced by the patient, to vary less with the radius of
the iris 5. This reduces another source of patient discomfort, and
thus is a further medical benefit.
[0199] (4) In some blended LALs 100, the radial variation of the
peripheral optical power 124 can be selected to induce a spherical
aberration that compensates a spherical aberration caused by the
cornea of the eye. This compensation can be partial, or an
essentially complete compensation. The implantation of such
spherical aberration-compensating blended LALs 100 can
advantageously minimize the imaging aberrations of the entire
ophthalmic system of the eye.
[0200] At least for the above reasons (1)-(4), and for further
reasons articulated below, the here-described embodiments of the
blended LAL 100 retain much of the medical benefits of the separate
EDOF and the CNA designs, while they mitigate and minimize the
undesirable side effects of these designs. These benefits also
characteristically distinguish the blended LAL 100 embodiments from
the mentioned pre-formed multifocal CNA IOLs, corneal inlays, and
CNA contact lens.
[0201] With reference to FIG. 13C, the first illumination 222 can
have any of the illumination patterns described in FIGS. 1-12, as
applicable, used to increase the depth of focus of the implanted
LAL. With reference to FIG. 13A and FIG. 14A, the lens materials
and lens optical properties of the LAL 100 can have any material
and property, described in relation to FIGS. 1-12, as
appropriate.
[0202] In the embodiments illustrated in FIGS. 13-19, the average
of the central optical power 114 is at least 0.5 diopter higher
than the average of the peripheral optical power 124. In some
embodiments, the central optical power 114 is at least 1.0 diopter
higher than the average of the peripheral optical power 124. As
such, the central region 110 is adapted to provide improved near
vision, and the peripheral annulus 120 provides improved distance
vision. In the embodiments of FIGS. 20A-C, the average of the
central optical power 114 is at least 0.5 diopter lower than the
average of the peripheral optical power 124. In some embodiments,
the average of the central optical power 114 is at least 1.0
diopter lower than the average of the peripheral optical power 124.
In these embodiments, the central region 110 is adapted to provide
improved distance vision, and the peripheral annulus 120 provides
improved near vision. Thus, the central region 110 can be called a
Central Near Add (CNA) region 110 for the embodiments of FIGS.
13-19, while for the embodiments of FIGS. 20A-C, the central region
110 can be referred to as Central Distance Add (CDA), or Peripheral
Near Add (PNA) region. These latter phrases are less widely
used.
[0203] In all the embodiments of FIGS. 13-30, the term "average"
can be defined in various suitable manners. For example, the
average can refer to an area integral of the optical power. In some
cases, only a portion, or fraction, of the total area of the
central region 110 and the peripheral annulus 120 can be used to
compute the average as an area integral. Such fractional
definitions of the average can be useful to de-emphasize, or
disregard non-representative deviations close to the pattern edge
126, or close to the region separating the central region 110 from
the peripheral annulus 120. The fractional area can be at least 25%
of the total area of either the central region 110, or the
peripheral annulus 120. In other embodiments, this can fractional
area can be 50%, 75%, or 90%. In other cases, the average can be
defined along a representative circle, or over a band, or with a
weighting function, or as a moment of a certain order of the
optical power.
[0204] FIGS. 14A-B illustrate the position of these regions
relative to the physical structure of the LAL 100. Prior to forming
the peripheral annulus 120 and the central region 110 in the LAL
100 by illuminations 222/242, the front and rear surfaces of the
LAL 100 typically have a single, approximately constant curvature,
and, accordingly, have an optical power that is either independent
of the position, or depends on it very weakly, only due to the
finite thickness of the LAL 100, for example.
[0205] After the LAL 100 is formed by applying a first illumination
222 to form the peripheral annulus 120, and then by applying a
second illumination 242, to form the central region 110, the
central axis 112 is often shifted relative to the LAL axis 102, in
order to compensate for the postsurgical shift and tilt of the LAL
100 that misaligned the LAL axis 102 with the visual axis 132 of
the eye with the iris 5 in its non-dilated state. Sometime the
annulus axis 122 also ends up being shifted relative to the LAL
axis 102. In the shown example, the central optical power 114 and
the peripheral optical power 124 meet at a sharp boundary. In other
examples, a smoother transition optical power 134 of a transition
130 can be between them.
[0206] FIG. 14B shows the LAL 100 of FIG. 14A, from the perspective
of the LAL axis 102, the relative positions of the central region
110 and the peripheral annulus 120, and the central axis 112 being
shifted relative to the annulus axis 122 by the axis shift 111.
[0207] The physical structure of the LALs 100 includes a lens edge
146, continuing in a LAL rim 148 to a LAL rim edge 149. The haptics
105 protrude well beyond the LAL rim edge 149, to wedge and to
stabilize the LAL 100 into the capsular bag emptied by the cataract
surgery. The pattern edge 126 of the first illumination 222
typically does not reach all the way to the lens edge 146, it stops
just before it. In some embodiments, the pattern edge 126 may
coincide with the lens edge 146, or even extend to the LAL rim 148,
that is initially flat and thus has no optical power. The LAL 100
typically also includes a UV (i.e. ultra-violet illumination)
absorbing layer 127. The first and second illuminations 222/242 are
applied from the side of the LAL 100 opposite of this UV absorbing
layer 127. A role of this UV absorbing layer 127 is to reduce the
transmitted portion of the illuminations to completely safe
levels.
[0208] FIGS. 13A-B and FIGS. 14A-B further illustrate that the LAL
100 can also include a transition 130, between the central region
110 and the peripheral annulus 120. The transition 130 can have a
transition optical power 134 that changes from the central optical
power 114 to the peripheral optical power 124. The overall
difference between the central optical power 114 and the peripheral
optical power 124 will sometimes be referred to as an optical power
change 136.
[0209] The double wavy lines indicate that the LAL 100 has an
additional, "base" optical power in the 5-35 diopters range,
typically within a few diopters of 20 diopters, whereas the
position dependent peripheral optical power 124 may vary 0.5-2
diopters in the peripheral annulus 120; the transition optical
power 134 may vary 0.5-2 diopters in the transition 130, and the
central optical power 114 may vary 0.1-1 diopters in the central
region 110, as an illustration. Broader ranges can be employed in
some embodiments. To avoid making the curve of the position
dependent optical powers 114, 124, and 134 uninformatively flat
relative to the much larger base optical power of 10-30 D, this
base optical power has been suppressed in the applicable Figures,
and only indicated with the double wavy line. In other words, the
optical power axis has been largely compressed in the relevant
Figures, such as in FIG. 13A.
[0210] FIGS. 15A-C illustrate the results of measurements of the
optical power as a function of the radial distance of the blended
LAL 100 in the main stages of the formation process, as indicated
in FIGS. 13C-D. Such optical power measurements can be performed by
several known methods and apparatuses, such as wavefront
measurement systems, and aberrometers, especially Shack-Hartmann
wavefront sensors, among others.
[0211] FIG. 15A shows the radially varying optical power prior to
the first illumination 222 in a LAL 100 that has a pre-molded
radially varying optical power, causing a spherical aberration. The
optical power OP varies from about OP=19.2 D at the lens edge 146
at around r=2.3 mm to OP=21.2 D at r=0, the LAL axis 102, yielding
an about 2 D radial optical power variation: .DELTA.OP=2D.
[0212] FIG. 15B illustrates the result of the same optical power
measurement after the first illumination 222 has been applied,
centered on an annulus axis 122, which in this case was chosen to
coincide with the LAL axis 102. At the lens edge 146 the OP got
enhanced to 20.8 D, while at the center to 22.8 D. Thus, the first
illumination 222 increased the average optical power of the LAL 100
by about 2 D, while preserved the radial optical power variation at
.DELTA.OP=2D in this case.
[0213] FIG. 15C shows the radially varying optical power of the
blended LAL 100 after the second illumination 242 has been also
applied to induce a CNA in a central region 110. The second
illumination 242 was centered on a central axis 112 that was
shifted from the annulus axis 122, as shown. Visibly, the overall
LAL optical power is a function of the radius in these blended LALs
100, and thus so is the overall focal distance. Accordingly, these
blended LALs 100 can be characterized as "polyfocal IOLs", or
"polyfocal LALs 100" as well.
[0214] In FIG. 15C, the central, or CNA, region 110 was formed over
a diameter of 1.5 mm. Within this central region 110 the central
optical power 114 is often intended to be quite smooth. FIGS. 15A-C
illustrate a precision of the above numerical values and ranges,
caused by natural measurement uncertainties and variations. The
variations of the optical power measurements are high for small
radii and decrease with increasing radius because the accuracy of
the measurement of a region's optical power is set by the area of
the region, and thus the variations are inversely proportional to
this same area. The quadratically smaller area of the central
region 110 compared to the peripheral annulus 120 explains that the
fluctuations of the measured central optical power 114 are visibly
greater than that of the peripheral optical power 124. FIG. 15C
illustrates that in some embodiments, measurements of the central
optical power 114 will exhibit an optical power variation 115, of
0.2 D. In other cases, the optical power variations 115 in the
central optical power 114 can be up to 0.4 D. FIG. 16 illustrates
that in some embodiments the central optical power 114 can have an
optical power variation 115 of a few tenth of diopters that arises
not from measurement-related fluctuations, but from the smooth
curving central optical power 114.
[0215] In some embodiments of the LAL 100, the central region 110
can directly meet the peripheral annulus 120 at a well-defined
boundary, making the transition 130 a sharp boundary; and the
central region 110 and the peripheral annulus 120 can meet at this
sharp boundary.
[0216] FIG. 13A, FIG. 15C and other Figures show that in some other
embodiments, the transition 130 can be a smoother transition
annular region between the central region 110 and the peripheral
annulus 120. The smoothness of the transition 130 can be captured
via ratios of relevant radii. FIG. 15C illustrates such relevant
radii: a radial width of the transition 130, .DELTA.RT 154, and an
outer radius RT 152 of the transition 130. In some embodiments, the
ratio .DELTA.RT/RT can be less than 0.3. In other embodiments,
.DELTA.RT/RT can be less than 0.5, in yet others, less than 0.7.
Here, a typical value for a radius RC 156 of the central region 110
can be in the range of 0.5 mm to 1.0 mm in some embodiments.
[0217] It is noted that statements and numerical ranges of the
optical properties, such as the optical power and the spherical
aberration, are meant within a context and a measurement protocol,
since these optical properties of the LAL 100 can be measured in
different ways, following different protocols that result in
different values.
[0218] (1) In one protocol, the LAL 100 can be characterized in
isolation, on an optical bench, where the LAL 100 is typically
immersed into a saline solution to mimic its optical performance in
the aqueous of the eye. Such measurements can be set up at least in
the following ways. (1a) Starting with a LAL 100 that has not been
light adjusted yet; then performing a light adjustment illumination
protocol as defined by the LAL manufacturer; and then measuring the
optical characteristics of the light-adjusted LAL 100 on the
optical bench. (1b) Implanting the LAL 100 into a patient's eye;
then performing the light adjustment illumination protocol in the
eye; then explanting the light-adjusted LAL 100 from the patient's
eye; and finally, measuring the optical characteristics of the
explanted LAL 100 again on the optical bench.
[0219] (2) In another protocol, the LAL 100 can be characterized
"in situ", as part of the overall ophthalmic optical system that
includes the LAL 100 and the cornea that has its own optical power
and own spherical aberration, the two lenses separated by a space
filled by the aqueous of the anterior chamber of the eye. Defining
such an "in situ" protocol can be particularly useful if the
optical power of an implanted LAL needs to be determined without
explanting the LAL from the patient's eye. Here we also describe
two related optical measurement approaches.
[0220] (2a) In the in situ protocol, the optical power of the
cornea 15, P.sub.c, and the optical power of the LAL, P.sub.LAL,
combine into the overall ophthalmic power P.sub.o, according to the
known formulae of two lens (telescopic) systems:
P.sub.o=P.sub.c+P.sub.LAL-d*P.sub.c*P.sub.LAL=P.sub.c+(1-d*P.sub.c)*P.su-
b.LAL (3)
[0221] where d is the separation between the cornea 15 and the LAL
100. Using typical values of P.sub.c about 40-45 D and d about 7
mm, a 1 D change in the optical power P.sub.LAL in the LAL plane
approximately translates to an about 0.7 D change in the overall
optical power P.sub.o in the corneal plane, defined approximately
as a plane at the vertex of the cornea 15.
[0222] Eq. (3) establishes a translation scheme between the
different types of optical power measurements. For example, if the
LAL optical power P.sub.LAL is adjusted by 1 D on the optical
bench, the adjusted LAL can be expected to cause an about 0.7 D
change of the ophthalmic optical power P.sub.o, when implanted in
the eye. And in reverse, if a light adjustment procedure is carried
out on an implanted LAL that is measured to cause a 1 D change of
the ophthalmic optical power P.sub.o in the corneal plane, and then
the LAL is explanted, the explanted LAL optical power P.sub.LAL can
be expected to show a power change of about 1 D/0.7=1.43 D in the
LAL plane.
[0223] (2b) Eq. (4) below shows that the optical power of the
entire eye ophthalmic optical system can be also calculated with an
analysis that includes more parameters and details, such as
additionally capturing beam propagation from the cornea to the
separately located spectacle plane. Eq. (4) below shows the change
in power of the implanted LAL, .DELTA.P.sub.LAL, necessary to
achieve a specific refractive correction of the eye at the
spectacle plane, R.sub.x, determined as the refractive correction
needed after the LAL 100 has been implanted into the eye. With the
notation of protocol (2a), R.sub.x=.DELTA.P.sub.o:
.DELTA. .times. P L .times. A .times. L = n A .times. q ( 1 n Aq 1
1 R x - d v + P c - d ELP - P c n A .times. q .times. P c .times. d
E .times. L .times. P ) ( 4 ) ##EQU00002##
[0224] Here, n.sub.Aq is the refractive index of the human aqueous,
PC is the corneal optical power, d.sub.ELP is the distance from the
apex of the cornea to the back principal plane of the implanted LAL
100, and d.sub.v is the vertex distance, i.e. distance from the
cornea to the spectacle plane. Typical values in Eq. (4) include a
corneal power P.sub.c=45 D, d.sub.ELP=4.5.times.10.sup.-3 m, and
n.sub.Aq=1.336. With these parameters, a desired refractive
correction R.sub.x=+1.5 D translates to a change in LAL power of
.DELTA.P.sub.LAL=+2.14 D. Taking the ratio of the desired spectacle
plane refractive correction R.sub.x=+1.5 D, to the required change
in LAL power, .DELTA.P.sub.LAL=+2.14 D, results in a translation
ratio of 0.70. This ratio essentially agrees with the 0.7
translation ratio determined from Eq. (3). Patient-to-patient
variations of the above parameters can lead to a plus-minus 3%
variation of this translation factor of 0.7. In other embodiments,
to a plus-minus 5% variation, or plus minus 10% variation.
[0225] Translation factors can be derived for the other optical
characteristics as well. For example, the spherical aberration, SA,
depends notably on the measurement diameter, aperture, or pupil.
(1) For isolated LALs, a natural definition of this pupil is in the
plane of the LAL. (2) However, for implanted LALs, the SA cannot be
directly measured at the LAL plane, and therefore a natural
definition of the pupil is in the corneal plane. From this, the
LAL-plane SA can be derived. A conversion, or translation factor
can be established between these two measurement positions based on
recalling the followings.
[0226] (2.1) The SA scales with the fourth power of the diameter,
and (2.2) a beam that is collimated at the cornea is focused down
by the corneal optical power P.sub.c to a decreasing diameter as it
propagates toward the implanted LAL. Using a representative corneal
power of P.sub.c=45 D, a diameter of a collimated beam incident on
the corneal plane gets reduced by about a factor of 0.85 by the
time it reaches the LAL plane. Equivalently, a diameter of a beam
propagating from the LAL out to the cornea increases by a factor of
1/0.85. Thus, e.g., a corneal beam diameter of 6 mm gets focused
down to a 5.1 mm LAL-plane beam diameter, and a corneal beam
diameter of 4.7 mm gets focused down to a 4.0 mm LAL-plane beam
diameter. It is customary to characterize the SA values of contact
lenses, positioned on the cornea, at a d=6 mm diameter. It is also
customary to characterize IOL SA values at a diameter of 4 mm,
which is, however, less than the diameter of a down-focused 6 mm
beam. Therefore, translating the d=6 mm corneal SA values into d=4
mm IOL SA values involves two conversion steps: the down-focus
factor of 0.85, and the ratio of diameters to the fourth power.
Thus, a LAL/IOL plane SA value, measured at 4 mm diameter is to be
converted to the diameter of 5.1 mm that corresponds to the 6 mm
corneal diameter by the down-focusing factor of 0.85. As a relevant
example, since (5.1 mm/4 mm).sup.4=2.6, a SA value of SA=0.1 .mu.m
at a 4 mm LAL-plane diameter corresponds to a SA=0.26 .mu.m at a 6
mm corneal-plane diameter. For patient corneas with different
corneal optical power, this correspondence factor can fall within a
range around 2.6, such as in the range of 2.2-3.0, in other cases,
2.4-2.8.
[0227] (3) The above SA values characterize the light adjusted
region. With reference to FIGS. 13A-B, 14A-B, this light adjusted
region extends to the pattern edge 126, typically inside the LAL
rim edge 149. Since the shape of the LAL 100 continues to change
outside the pattern edge 126, SA values that are measured with
diameters past the pattern edge 126 are impacted by the LAL rim
148, and tend to be different from SA values measured at diameters
inside the pattern edge 126. In some cases, the SA can even change
sign when measured with the rim included.
[0228] In some blended LAL 100s, it can be medically beneficial for
the central optical power 114 to have only a limited spatial
variation, and a corresponding approximately flat
position-dependence, since limiting spatial variations limits the
aberration of the imaging, and thus improves the visual acuity. In
these "flat top" embodiments, the central region 110 can have an
optical power variation less than 0.2 diopters over 50% of the
central region 110, resulting in high visual acuity. In other
embodiments of blended LALs 100, the central optical power 114 can
be a function of a radius from the central axis 112, having an
optical power variation 115 greater than 0.2 diopters over 50% of
the central region 110. These embodiments may be emphasizing the
presbyopia mitigation benefit.
[0229] Analogously, in some embodiments of the LAL 100, the
peripheral optical power 124 can have an approximately flat
position-dependence, having an optical power variation less than
0.2 diopters over 50% of the peripheral annulus. In related
embodiments, the peripheral optical power 124 can be a function of
a radius from the annulus axis 122, having an optical power
variation greater than 0.2 diopters over 50% of the peripheral
annulus.
[0230] FIGS. 17A-B and 18 illustrate how the LAL 100 with the above
characteristics mitigates the presbyopic medical needs, described
earlier. One of the most widely used measure of a patient's vision
is the Visual Acuity (VA), which records the ratio of a distance a
patient has to stand from an eye chart to achieve the same visual
clarity as a person with normal eyes achieves from 20 feet. There
are closely related conventions to determine this VA value, such as
the Snellen VA and the Early Treatment Diabetic Retinopathy Study
(ETDRS) VA. Another measure is the log MAR, where "MAR" abbreviates
"Minimal Angle Resolved", and "log" references that the logarithm
of this angle is taken for this measure. These measures are
determined based on the subjective feedback of the patient,
typically by asking the patient to report which letters in which
lines he/she can see clearly on the eye chart, from different
distances. In practice, changing the viewing distance is often
simulated by inserting lenses of varying diopters in front of the
patient, using a phoropter. Typically, these tests are reported
after incorporating a correction to infinite viewing distances.
Thus, in FIGS. 17A-B and FIG. 18, 1D corresponds to a viewing
distance of 1 m, etc. These two measures can be translated to each
other, as shown in Table 8:
TABLE-US-00008 TABLE 8 VA logMAR 20/40 0.3 20/32 0.2 20/25 0.1
20/20 0.0 20/16 -0.1 20/12.5 -0.2 20/10 -0.3
[0231] It is customary to accept log MAR values smaller than 0.2
(i.e. VA values better than 20/32), as indications of good, or
satisfactory visual acuity. (Following convention, the negative log
MAR values are at the top of the axis, and they grow to positive
log MAR values at the bottom of the axis. Therefore, log MAR values
"smaller than 0.2" are in fact above the log MAR=0.2 line in FIGS.
17-18.) With this preparation, FIGS. 17A-B and 18 demonstrate the
problem of presbyopia and the improved visual acuity delivered by
the blended LALs 100. A young eye has an easily deformable
crystalline lens, and therefore can accommodate to a wide range of
viewing distances. This is seen in FIG. 17A by the base of the log
MAR curve, i.e. the range of diopters with log MAR values smaller
than 0.2, covering the wide range from +1.5 D to -2.5D. In viewing
distances, this translates to good visual acuity from (1/2.5D)=40
cm out to infinity, and beyond, to virtual targets. In terms of a
depth of focus, or DOF, this young eye exhibits a
DOF(young)=+1.5D-(-2.5D)=4D.
[0232] An older, presbyopic eye is gradually losing its ability to
accommodate to different viewing distances. Presbyopia is, in fact,
Greek for "old eyes", or "old sight". E.g., the DOF of the shown
presbyopic eye decreased to DOF(presbyopic)=+0.5D-(-0.5D)=1D,
approximately.
[0233] FIG. 17B illustrates the two presbyopia solutions, discussed
earlier. (1) IOLs with an Extended Depth of Focus, or EDOF IOLs are
formed with a radially varying optical power that extends the focal
point into an elongated focal region. The adaptiveness of the human
vision enables the patient's brain to extract images created with
this elongated focal region, to see targets in a wider range. This
adaptiveness smoothly broadens the log MAR curve, extending the DOF
to DOF(EDOF)=+0.5D-(-1.5D)=2D.
[0234] (2) IOLs with a Central Near Add (CNA) introduce a more
distinctly defined second focal region, and thus broaden the log
MAR curve unevenly by introducing a second maximum. The illustrated
CNA IOL has a DOF(CNA)=+0.5D-(-2.5D)=3D, approximately. While both
of these presbyopic techniques extend the DOF and thus mitigate
presbyopia by improving visual acuity over an extend range of
target distances, they do so by introducing drawbacks, as was
discussed earlier. The log MAR curve articulates these drawbacks
further. EDOF IOLs extend the DOF to a medium degree. CNA IOLs
extend the DOF better than EDOF IOLs, DOF(CNA)>DOF(EDOF).
However, they do so at the expense of a noticeable reduction of the
midrange visual acuity, as shown by the pronounced log MAR minimum
around -0.5D.
[0235] FIG. 18 illustrates the log MAR curve of the blended LALs
100, which blend the EDOF and the CNA techniques. (1) Visibly, the
blended LALs 100 extend the medium DOF of the EDOF IOLs from
DOF(EDOF)=2D to the longer DOF of the CNA IOLs:
DOF(EDOF+CNA)=3-3.5D. (2) Importantly, the blended EDOF+CNA LALs
100 also largely eliminate the midrange log MAR minimum of the CNA
IOLs. To sum, the blended EDOF+CNA LALs 100 deliver the longer DOFs
of the CNA IOLs, as well as the no-midrange-minimum smoothness of
the EDOF IOLs. In other words, blended LALs 100 deliver the
positives of the two existing presbyopia IOLs, while eliminating
their drawbacks.
[0236] FIGS. 13-18 illustrated blended LALs 100, where (1) the
central optical power 114 was higher than the peripheral optical
power 124, at least in an average sense. Also, the optical power
was a decreasing function of the radius (2) in the central region
110, and (3) in the peripheral annulus 120, shown by the downward
curvatures of the optical power curves in both of these regions.
These three design factors (1)-(3) can be combined in 23=8
different ways, defining 8 possible embodiments of the blended LALs
100. All 8 combinations can offer advantages for visual
challenges.
[0237] FIGS. 19 and 20A-C illustrate four of these eight possible
combinations of the design factors. In FIG. 19, the central optical
power 114 is still greater than the peripheral optical power 124,
and the central optical power 114 still has a downward curvature.
However, the peripheral optical power 124 has an upward curvature.
Such optical designs also have an extended depth of focus, but the
geometric relation between light rays from larger radii and smaller
radii is reversed. In this design, the peripheral annulus 120 does
not extend the depth of focus beyond the DOF extension induced by
the central region 110. Instead, an advantage of the design of FIG.
19 is that it "fills in" the midrange log MAR minimum even more
efficiently than previously described designs, thereby delivering
an improved overall visual acuity.
[0238] FIGS. 20A-C show three embodiments, where the central
optical power 114 is less than the peripheral optical power 124, at
least in the above defined average sense. In these LALs 100, the
central region 110 is providing good distance vision and the
peripheral annulus 120 provides good near vision. In this sense,
these embodiments and designs can be called Central Distance Add
(CDA) LALs, or Peripheral Near Add (PND) LALs. These are less
frequently used terms, as mentioned before.
[0239] In FIG. 20A, the central optical power 114 and the
peripheral optical power 124 are both decreasing functions of the
radius. In FIG. 20B, the central optical power 114 increases with
the radius, while the peripheral optical power 124 decreases with
the radius. In FIG. 20C, the central optical power 114 and the
peripheral optical power 124 are both increasing functions of the
radius.
[0240] In any of the above embodiments of the blended LAL 100, the
central optical power 114 can be a quadratic function of the radius
from the central axis 112 over the central region 110, optionally
having a small correction term, or can have a quadratic component.
In some of the cases, the peripheral optical power 124 can be a
quadratic function of the radius from the annulus axis 122 over the
annular region 120, optionally with a small correction term, or can
have a quadratic component. To characterize these embodiments, it
is recalled that the radius dependent optical power P(r) is related
to the wavefront W(r) as:
P .function. ( r ) = 1 r .times. dW .function. ( r ) dr ( 5 )
##EQU00003##
[0241] Therefore, the above-described quadratic functions or
components of the optical power P(r) correspond to a wavefront
aberration proportional to the fourth power of the radius. The
simplest fourth order aberration is the angle independent spherical
aberration, or SA, its coefficient often denoted by Z(4,0), or Z12
in Zernike notation. Thus, embodiments of the blended LAL 100,
where the position dependence of the optical power P(r) has a
quadratic function or component, can be also characterized by a
corresponding spherical aberration. Below, ranges of the spherical
aberrations SA of some blended LALs 100 will be characterized. The
described SA values can be induced by the peripheral optical power
124 alone, or by a combination of the central optical power 114,
the peripheral optical power 124, and the transition optical power
134 of the blended LAL 100. An example of the former case is a
pre-molded LAL 100, where a spherical aberration has been molded
into the LAL 100, including into its peripheral annulus 120,
measured before the central region 110 has been formed. An example
of the latter case is a LAL 100, where the central region 110 has
been already formed, typically after implantation.
[0242] In some blended LALs 100, the spherical aberration with one
of the above definitions can be in the -0.05 .mu.m to -1 .mu.m
range at a diameter of 4 mm in a plane of the LAL. In some
embodiments, the spherical aberration can be in the -0.05 .mu.m to
-0.35 .mu.m range at a diameter of 4 mm in a plane of the LAL. In
yet other embodiments, the spherical aberration can be in the -0.10
.mu.m to -0.25 .mu.m range at a diameter of 4 mm in a plane of the
LAL.
[0243] As noted above, these LAL-plane SA values translate to SA
values measured at a 6 mm diameter at the corneal plane
approximately by a scale factor of about 2.6, or in a range around
2.6, such as the range of 2.4-2.8, or 2.2-3.0. Since the
translation factor can vary over these narrow, but finite ranges,
corneal plane SA values will be expressly described next. This
translation of the SA values can be particularly useful if the SA
of an implanted LAL 100 needs to be determined without explanting
the LAL 100 from the patient's eye. For example, the -0.05 .mu.m to
-1 .mu.m SA range at a diameter of 4 mm at the LAL plane can
translate to an approximately -0.13 .mu.m to -2.6 .mu.m SA range at
a diameter of 6 mm in the corneal plane. In other embodiments of
the blended LAL 100 implanted in an eye, the SA, measured at a 6 mm
diameter at the corneal plane, can be in the range of -0.05 .mu.m
to -2 .mu.m; in yet other embodiments, in the range of -0.1 .mu.m
to -0.6 .mu.m, or in the range of -0.2 .mu.m to -0.4 .mu.m.
[0244] As described next, when the spherical aberration is measured
in an eye with an implanted LAL 100, the measurement results will
be impacted by the spherical aberration of the eye before the
implantation. Therefore, the SA attributed to the implanted LAL 100
alone is to be extracted from the SA values measured for the entire
eye.
[0245] In the context of measuring the SA of an eye with an
implanted LAL 100, it is recalled that the cornea has its own
spherical aberration SA(cornea). Over a large patient population
this corneal SA(cornea) has a distribution. An average, or mean, of
this distribution is described in some studies to be around
SA(cornea)=+0.26 .mu.m, with a standard deviation of about .+-.0.13
.mu.m at the corneal plane with a 6 mm diameter. Other studies
report mean values between +0.20 .mu.m and +0.30 .mu.m, with
correspondingly varying standard deviation. The SA of the combined
ophthalmic optical system of the cornea 15 and the implanted LAL
100 will have an SA(combined)=SA(LAL)+SA(cornea), with both SA
values measured at the same plane and radius. For example, if the
LAL 100 is known to have a SA in the range of -0.10 .mu.m to -0.25
.mu.m at a 4 mm diameter in the LAL plane, then first this SA is to
be translated to a SA at a 6 mm diameter in the corneal plane.
Using the translational factor of 2.6, corresponding to the average
corneal power, the SA(LAL, d=4 mm, LAL plane)=-0.10 .mu.m to -0.25
.mu.m range translates to a SA(LAL, d=6 mm, corneal plane)=-0.26
.mu.m to -0.65 .mu.m range. Second, the SA of the combined
ophthalmic optical system of the cornea 15 and the implanted LAL
100 can be determined by combining this SA(LAL, d=6 mm, corneal
plane) with the SA(cornea) of the cornea at the same 6 mm diameter
in the same corneal plane: SA(combined)=SA(LAL, d=6 mm, corneal
plane)+SA(cornea). With the above values, SA(combined) at the 6 mm
diameter in the corneal plane in embodiments can be in the range of
0 .mu.m to -0.39 .mu.m in case of an eye with an average
SA(cornea). In other embodiments, again measured at d=6 mm at the
corneal plane, the combined spherical aberration of an eye with an
implanted LAL 100, the SA(combined) can fall within the -0.05 .mu.m
to -0.5 .mu.m range. In yet other embodiments, SA(combined) can
fall in the -0.1 .mu.m to -0.2 .mu.m range.
[0246] The same consideration can be used in reverse to determine
the SA(LAL, d=6 mm, corneal plane) of a LAL 100 implanted into the
eye of a particular patient, by measuring the SA(combined) of the
patient's eye, and then subtracting from it the patient's specific
corneal SA(cornea). From the so-determined SA(LAL, d=6 mm, corneal
plane), the SA(LAL, d=4 mm, LAL plane) can then be determined by
the above translation factor, as needed.
[0247] Another calculus can be useful to reconstruct SA(pre-mold),
the pre-molded portion of the SA for an implanted LAL 100, where
the CNA, or central region 110 has been already formed. This
SA(pre-mold) can be related to the entire LAL 100, or to the
peripheral annulus 120. After the implantation of the LAL 100, the
SA(pre-mold) is shifted with a .DELTA.SA(CNA) by the formation of
the CNA, or central region 110. Therefore, the SA(pre-mold) can be
reconstructed by measuring the SA of the entire implanted LAL 100,
and then subtracting appropriate .DELTA.SA(CNA) values. In some
embodiments, at d=6 mm in the corneal plane, .DELTA.SA(CNA) can
take values in the -0.01 .mu.m to -0.4 .mu.m range, in others in
the -0.05 .mu.m to -0.2 .mu.m range. The formation of the CAN, or
central region 110 often shifts the SA(LAL) value relatively little
because the diameter of the CAN, or central region 110 is often
small, in the range of 0.5 mm to 1.5 mm, and the value of the
spherical aberration SA scales with the fourth power of the
diameter.
[0248] In some embodiments of the blended LAL 100, a spherical
aberration caused by the position-dependence of the central optical
power 114, the peripheral optical power 124, or their combination,
can be selected to approximately compensate a spherical aberration
of the cornea 15 of the eye. In such embodiments, the optical
aberrations of the combined optical system of the cornea 15 and the
LAL 100 are minimized.
[0249] For completeness, it is mentioned that once the central
region 110 and the transition 130 have been formed, the latter with
its fast-changing transition optical power 134, the optical powers
114/124/134 often deviate substantially from a quadratic function
of the radius, and thus induce higher order aberrations beyond the
Z(12) spherical aberration.
[0250] Another type of aberration, a coma is induced when an IOL
with a pre-molded spherical aberration (an SA IOL) is shifted off
the optical axis. In Zernike notation, the coma is represented by
the Zernike coefficient Z8, and the spherical aberration by Z12. A
.DELTA.x off-axis shift of an SA IOL induces a coma given by Eq.
(6):
Z .times. 8 = 2 .times. 1 .times. 0 .times. .DELTA. .times. x
.times. Z .times. 1 .times. 2 r . ( 6 ) ##EQU00004##
[0251] Embodiments of the LAL 100 can mitigate this coma
aberration, even if the LAL 100 is shifted off-axis. Using
embodiments of the LAL 100 where the peripheral annulus 120 is
formed only after the LAL 100 settled can preempt this problem
entirely, as the peripheral annulus 120 can be formed with an
annulus axis 122 that is centered on the visual axis 132. In some
cases, this can be achieved by shifting the annulus axis 122 with a
shift that is equal and opposite to the .DELTA.x off-axis shift of
the LAL 100. The peripheral annulus 120 can be centered on the
visual axis 132, e.g., by registering the visual axis 132 prior to
dilating the iris 5.
[0252] In some embodiments of the blended LAL 100, further
aberrations of the patient's vision can be mitigated. A notable
example is that in some LALs 100 the position-dependent central
optical power 114 can involve a cylinder angular dependence. In
some LALs 100 the position-dependent peripheral optical power 124
can involve a cylinder angular dependence. Forming a cylinder in
either the central region 110 or in the peripheral annulus 120 can
mitigate an existing cylinder in the patient's eye.
[0253] FIGS. 21A-B illustrate that some embodiments of the blended
LALs 100 can include an annular mid-range vision region 150,
positioned between the central region 110 and the peripheral
annulus 120. The mid-range optical power 154 of this mid-range
vision region can be selected to improve vision at medium ranges,
such as at distance around 1 meter. An axis of the mid-range vision
region 150 can coincide with the LAL axis 102, the central axis
112, or the annulus axis 122. In some aspects, the mid-range vision
region 150 may be viewed as part of the transition 130.
[0254] In some embodiments of the LAL 100, the first illumination
222 induces the position-dependent peripheral optical power 124,
and the second illumination 242 induces the position-dependent
central optical power 114 primarily by inducing a shape change of
the LAL 100 via activating a photopolymerization process. In other
embodiments, the same illuminations 222 and 242 induce the optical
powers 114 and 124 primarily by changing an index of refraction of
the LAL 100, in effect transforming the LAL 100 into a Gradient
Index of Refraction, or Graded Index of Refraction, (GRIN) lens. In
yet other embodiments, the illuminations 222 and 242 induce the
optical powers 114 and 124 by a combination of shape change and
index of refraction change.
[0255] FIG. 22 illustrates a unifying aspect of the LALs 100b
depicted in FIGS. 13-21. In broader terms, a Light Adjustable Lens
(LAL) 100b can have a LAL axis 102b, and include a light-adjusted
region 310r, centered on an adjustment axis 312, with a
position-dependent adjusted optical power 314; wherein the
adjustment axis 312 can be laterally shifted relative to the LAL
axis 102b. The embodiments of FIGS. 13-21 are specific embodiments
of this general LAL 100b design, where, e.g. the adjusted optical
power 314 includes the central optical power 114, the peripheral
optical power 124, or both. A unifying aspect of these embodiments
is that, because they have an adjusted optical power 314 that was
formed by adjusting the implanted LAL 100 after it settled and
often shifted from its intended position in the capsular bag, the
adjustment axis 312 is laterally shifted relative to the LAL axis
102b.
[0256] To relate the light-adjusted region 310r to the physical
structure of the LAL 100b, beyond a pattern edge 126b, these LALs
100b can include a lens edge 146b, a LAL rim 148b, and a LAL rim
edge 149b, as in FIGS. 14A-B.
[0257] FIG. 23 illustrates a distinct case of a LAL 100c, where the
central axis 112 is not shifted relative to the annulus axis 122;
instead it coincides with it. In the shown embodiment of LAL 100c,
the central axis 112, the annulus axis 122 and the LAL axis 102 all
coincide. This embodiment may emerge in multiple ways. One of them
is that the visual axis 132 is determined after the iris 5
approximately returned into its non-dilated state, for example,
during a subsequent office visit, and the surgeon found that none
of the misalignment mechanisms (1)-(4) shifted the LAL axis 102
from the visual axis 132, and thus the central region 110 can be
formed centered on the shared central axis 112/LAL axis 102.
Another possibility is that for some reason, such as to reduce the
number of office visits, the surgeon decides to form the
CNA/central region 110 while the iris 5 is still dilated, in which
case it is reasonable to form the CNA/central region 110 with a
central axis 112 that coincides with the annulus axis 122. All
aspects, details and descriptions related to the embodiments of
FIGS. 13-22 can be combined with the blended LAL 100c of FIG.
23.
[0258] FIGS. 24-30 describe methods of light adjustment of the
blended LALs 100. FIG. 24 shows that a method 200 of adjusting a
Light Adjustable Lens (LAL) 100 can include the following steps.
[0259] Implanting 210 a LAL 100 into an eye; [0260] Applying 220 a
first illumination 222 to the LAL 100 with a first illumination
pattern 224 to induce a position-dependent peripheral optical power
124 in at least a peripheral annulus 120, centered on an annulus
axis 122; [0261] Determining 230 a central region 110 and a
corresponding central axis 112 of the LAL; and [0262] Applying 240
a second illumination 242 to the LAL 100 with a second illumination
pattern 244 to induce a position-dependent central optical power
114 in the central region 110 of the LAL 100; wherein [0263] (250)
the central axis 112 is laterally shifted relative to the annulus
axis 122 of the peripheral annulus 120, and [0264] (260) an average
of the central optical power 114 is at least 0.5 diopters different
from an average of the peripheral optical power 124.
[0265] In embodiments of the method 200, the average of the central
optical power 114 can be at least 1.0 diopter different from the
average of the peripheral optical power 124.
[0266] In some embodiments, the average of the central optical
power 114 can be at least 0.5 diopters higher than an average of
the peripheral optical power 124. The LALs 100 formed with such
embodiments can be called Central Near Add, or CNA LALs. In other
embodiments, the average of the central optical power 114 can be at
least 0.5 diopters lower than an average of the peripheral optical
power 124. The LALs 100 formed with such embodiments can be called
Central Distance Add (CDA), or Peripheral Near Add (PNA) LALs.
[0267] In some embodiments of the method 200, the applying 220 of
the first illumination 222 can include applying the first
illumination 222 with a first illumination pattern 224 to induce
the position-dependent peripheral optical power 124 in a
light-adjusted region that includes the peripheral annulus 120 and
the central region 110. In other embodiments, the first
illumination pattern 224 is concentrated mostly on the peripheral
annulus 120, and an amplitude of the first illumination pattern 224
can be greatly reduced in the central region 110.
[0268] As described in relation to FIGS. 13-23, an advantage of the
design of the blended LAL 100 is that its central axis 112 can be
aligned with the eye's visual axis 132. Accordingly, in embodiments
of the method 200, the determining 230 of the central axis 112 can
include identifying the visual axis 132 of the eye as the central
axis 112.
[0269] FIGS. 25A-B illustrate that, since the iris 5 can return to
its non-dilated state in an asymmetric manner, this determining
step 230 of the central axis 112 can be performed with an iris 5 of
the eye being in, or returned to, a non-dilated state in order to
achieve a good alignment with the visual axis 132. In related
embodiments, the eye does not need to fully return to its
non-dilated state. In these embodiments, the determining 230 of the
central axis 112 can include determining the central axis 112 with
the iris 5 of the eye being dilated to an iris-radius no more than
30% greater than a non-dilated iris-radius. In other words, to
perform the determining 230 when the iris is only in the process of
returning to its non-dilated state, but the return is only partial
and the iris did not reach the non-dilated state fully.
[0270] In some other embodiments of the method 200, the determining
230 of the central axis 112 can include determining the central
axis 112 before the iris 5 of the eye is dilated and registering
the determined central axis 112 with a feature of the eye. In these
embodiments the determined and registered central axis 112 can be
reconstructed after the iris is dilated, but before the applying
240 of the second illumination 242. In some cases, the registration
of the determined central axis 112 can be carried out with respect
to retinal features, in other cases, with respect to features of
the iris, limbus, or sclera of the eye. The determining of the
central axis 112 can involve determining the visual axis 132 of the
eye with the iris 5 being non-dilated, and then simply defining the
central axis 112 as the determined visual axis 132. An advantage of
this approach is that the doctor does not have to wait during the
surgery for the iris 5 to slowly return to its largely non-dilated
state; or, does not have to schedule a separate subsequent
procedure to apply the second illumination 242.
[0271] In this embodiment of the method 200, the sequence of the
applying 220 of the first illumination 222 and the applying 240 of
the second illumination 242 can be interchanged, since the
availability of the registered central axis 112 eliminates the need
to wait for the iris 5 to relax after the applying 220. The
sequence of the applying step 220 and the applying step 240 can be
also interchanged in embodiments of the method 200 where the iris 5
is dilated not at the beginning of the procedure, but only after
the firstly-performed applying 240 of the second illumination 242
has been completed. Finally, in some embodiments, the applying 240
of the second illumination 242 can be performed before the applying
220 of the first illumination 222, both with the iris dilated. In
these embodiments, it may be somewhat challenging to align the
central axis 112 with the visual axis 132.
[0272] As shown in FIGS. 13-23, the applying 220 of the first
illumination 222 and the applying 240 of the second illumination
242 can induce a transition 130 between the central region 110 and
the peripheral annulus 120, having a transition optical power 134
that changes from the central optical power 114 to the peripheral
optical power 124.
[0273] FIG. 16 illustrates that the method 200 can be performed to
create "flat top" blended LALs 100. In these LALs 100 the central
optical power 114 can have an approximately flat
position-dependence, having an optical power variation less than
0.2 diopters over a central 50% of the central region 110. In some
other embodiments, the central optical power can have an optical
power variation greater than 0.2 diopters over the central 50% of
the central region 110.
[0274] As before, the central optical power 114 can be a quadratic
function of the radius from the central axis 112 over a quadratic
central region, optionally having a small correction term. As
described in relation to Eq. (5), such a quadratic radius
dependence of the optical power induces a fourth order spherical
aberration, discussed further below.
[0275] Also, in some embodiments, the peripheral optical power 124
can have an approximately flat position-dependence, having an
optical power variation less than 0.2 diopters over 50% of the
peripheral annulus 120. In other embodiments, the peripheral
optical power 124 can be a function of a radius from the annulus
axis 122, having an optical power variation greater than 0.2
diopters over 50% of the peripheral annulus 120. The peripheral
optical power 124 can be a quadratic function of the radius from
the annulus axis 122 over a quadratic annular region, optionally
with a small correction term.
[0276] The mentioned quadratic radius dependence of the peripheral
optical power 124 can also induce, or cause, a spherical aberration
(SA) in the -0.05 .mu.m to -1 .mu.m range at a diameter of 4 mm in
a plane of the LAL 100. In some embodiments, the spherical
aberration caused by the position-dependence of the peripheral
optical power 124 can be in the -0.10 .mu.m to -0.25 .mu.m range at
a diameter of 4 mm in a plane of the LAL 100. These LAL-plane, d=4
mm diameter SA values can be translated into corneal plane, d=6 mm
SA values with a translation factor, which in a wide class of cases
is about 0.26, as calculated earlier.
[0277] In some embodiments of the method 200, at least one of the
central optical power 114 and the peripheral optical power 124 can
be selected such that a spherical aberration caused by the
position-dependence of the selected central optical power 114 or
peripheral optical power 124 approximately compensates a spherical
aberration of the cornea 15 of the eye. As described before, such a
selection can minimize, or even eliminate, the inducing of
aberrations in the eye's optical system, by a postsurgical shift of
the LAL 100.
[0278] In embodiments of the method 200, the applying 220 of the
first illumination 222, or the applying 240 of the second
illumination 242 can further include inducing the
position-dependent central optical power 114 with a cylinder
angular dependence, or inducing the position-dependent peripheral
optical power 124 with a cylinder angular dependence. These
embodiments of the method 200 can mitigate not only presbyopia, but
also cylinder aberrations of the eye. The inducing of a cylinder in
the central region 110 or in the peripheral annulus 120 can be
performed before, simultaneously, or after the applying steps 220
or 240. The numerous sequences and combinations of the (1) applying
220 of the first illumination 222; (2) applying 240 of the second
illumination; and (3) inducing the cylinder, can all be embodiments
of the method 200.
[0279] In some embodiments of the method 200, the applying 220 of
the first illumination 222 and the applying 240 of the second
illumination 242 can be separated by less than 48 hours. In some
embodiments, these two applying steps 220 and 240 can even be
performed as part of a single, integrated procedure, separated by
only a short time, thus reducing the demands on the surgeon and the
patient.
[0280] Also, once all the light adjusting steps of the method 200
have been performed, a lock-in illumination can be applied to the
LAL 100, in order to lock in the induced peripheral optical power
124 and the induced central optical power 114 in the LAL 100. This
step can be necessary to lock in the specific shape of the LAL 100
by de-activating all remaining photopolymerizable macromers still
in the LAL 100, as described, e.g., in the incorporated U.S. Pat.
No. 6,905,641, to Platt et al, and in U.S. Pat. No. 7,281,795, to
Sandstedt et al., among others.
[0281] FIG. 26 and FIGS. 27A-B illustrate an additional advantage
of the method 200. In some cases, the patient may ask the surgeon
to form the CNA central region 110 in the implanted LAL 100, but
after the procedure may be dissatisfied with the outcome and demand
a corrective procedure. This can happen if the CNA central region
110 caused undesired or disorienting blurriness, or halos, or both.
Had the surgeon implanted a non-light-adjustable CNA IOL, such a
patient demand would be impossible to satisfy. In contrast, having
implanted a blended LAL 100 enables the surgeon to perform a "CNA
erasure" process. The surgeon may perform an applying 270 of a
third illumination 272 to the LAL 100 with a third illumination
pattern 274 centered on the central axis 112 to reduce the
position-dependent central optical power 114, induced in by the
second illumination 242 in the central region 110 of the LAL 100.
FIG. 27A, left panel re-describes the LAL 100 as formed by the
steps 210-260 of the method 200. FIG. 27A, right panel illustrates
that performing of the additional applying step 270 of the third
illumination 272 to reduce the central optical power 114. This
reduction is captured, e.g., in that the optical power change 136
between the central optical power 114 and the peripheral optical
power 124 is visibly reduced by the applying 270 of the third
illumination 272. FIG. 27A, central panel shows a third
illumination pattern 274 that is intense in the peripheral annulus
120 but has low intensity in the central region 110, and therefore
can be suitable for the applying 270 of the third illumination
272.
[0282] FIG. 27B illustrates that the applying the third
illumination 272 can largely restore the patient's visual acuity.
The plot shows an often-used measure of visual acuity, the
Modulation Transfer Function, or MTF, as a function of its natural
variable, the frequency, measured in line pairs per mm, or lp/mm.
Visibly, the MTF gets reduced from its value prior to the second
illumination 242 that formed the CNA central region 110 to lower
values after the second illumination 242, since the CNA central
region 110, while it improves the patient's near vision, it also
enhances optical various aberrations. The reduction is more
pronounced at higher frequencies. Importantly, the plot
demonstrates that the MTF can be restored to essentially the
pre-second-illumination levels by applying of the third
illumination 272.
[0283] In some embodiments, after the second illumination 242 the
patient may be dissatisfied with the outcome and demand a
corrective procedure, but with an opposite goal. The patient may
report to the doctor no visual acuity problems caused by the CNA
central region 110, but instead may find that not enough power was
added. In such cases, the third illumination 272 may be used with a
third illumination pattern 274 to enhance the central optical power
114 in the central region 110.
[0284] FIG. 28 illustrates a method 300 of adjusting the Light
Adjustable Lens (LAL) 100, related to the method 200. The method
300 can comprise the following steps. [0285] Implanting 310 a LAL
100 into an eye, the LAL 100 having a pre-molded position-dependent
peripheral optical power 124 in at least a peripheral annulus 120,
centered on an annulus axis 122; [0286] Determining 320 a central
region 110 and a corresponding central axis 112 of the LAL 100; and
[0287] Applying 330 a central illumination 342 to the LAL 100 with
a central illumination pattern 344 to induce a position-dependent
central optical power 114 in the central region 110 of the LAL 100;
wherein [0288] (340) The central axis 112 is laterally shifted
relative to the annulus axis 122, and [0289] (350) An average of
the central optical power 114 is at least 0.5 diopters different
from than an average of the peripheral optical power 124.
[0290] A difference between the method 200 and this method 300 is
the manner in which the position dependent peripheral optical power
124 is formed. In the method 200, the peripheral optical power 124
is formed by the applying 220 of the first illumination 222 to the
already implanted LAL 100. In contrast, in the method 300, this
same peripheral optical power 124 is pre-formed, prior to the
implantation of the LAL 100, during the molding process of the
manufacture of the LAL 100. A benefit of the method 200 is that the
positioning and the magnitude of the peripheral annulus 120 can be
adjusted based on a measurement of the postsurgical shifts of the
LAL 100. Another benefit is that the magnitude and position
dependence of the peripheral optical power 124 can be customized to
the individual need of the specific patient. A drawback can be that
doing so may require an additional procedure, with the necessary
scheduling and organization and an extra trip for the patient. (It
is noted that this demand can be reduced in some cases by
performing the applying step 220 and the applying step 240 during a
single visit by the patient. This may require accelerating the iris
5 returning to its non-dilated state by pharmacological means.)
[0291] In contrast, benefits of the method 300 include that it
starts with a LAL 100 that already has a pre-molded
position-dependent peripheral optical power 124. In a sense, this
method 300 starts with an EDOF LAL, and the method concentrates on
adding a CNA to this EDOF LAL. Therefore, the method 300 does not
require the applying 220 of the first illumination 222, and thus
has one less procedure step. This beneficially reduces the number
of office visits for the patient. Potential drawbacks include that
the positioning of the peripheral annulus 120 and the magnitude of
the peripheral optical power 124 may not be adjusted in response to
a measurement of the postsurgical shift of the LAL 100.
[0292] However, simple geometric considerations suggest that the
total optical power accommodation necessary to mitigate presbyopia,
i.e. to cover the range from near targets (d=0.4-0.5 m, i.e. 2-2.5
D) to distance targets (approx. 0 D) is about 2-2.5 D. This is to
be delivered by the combination of the higher central optical power
114 of the CNA central region 110 and the position-dependent
variation of the EDOF peripheral optical power 124. Therefore,
embodiments of the LAL 100 that combine a pre-molded optical power
124 with a radial variation of 0.5-1 D with a customized addition
of 1-2D of central optical power 114 post-implantation, may be able
to deliver all the benefits of the blended CNA+EDOF LAL designs,
even without customizing the peripheral optical power 124 by
applying 220 the first illumination 222 post-implantation.
Moreover, surgeons may be provided with a series of LALs with
different amounts of radial peripheral optical power variations,
and thus different SAs, pre-molded into them. This may enable the
surgeon to select a LAL with the pre-molded SA and position
dependent peripheral optical power 124 that is most suitable for
the patient's individual need. All in all, both the method 200 and
the method 300 have advantages and drawbacks, and the surgeon may
decide between them based on the needs of the individual
patient.
[0293] Regarding the physical realization of the pre-molded EDOF
LALs, the position dependence of the peripheral optical power 124
can be pre-molded on the front of the LAL 100, on its back, or in
combination both in the front and in the back.
[0294] All aspects of the blended LALs 100 shown in FIGS. 13-23,
and all aspects of the method 200 shown in FIGS. 24-27, can be
combined with embodiments of the method 300. One aspect is
mentioned specifically: not only the position variation of the
peripheral optical power 124 can be pre-molded, but potentially a
cylinder can be also pre-molded into the LAL 100.
[0295] FIG. 29 illustrates that the above two methods, method 200
and method 300 can be thought of as subcases of a more generally
articulated method 400 of adjusting the Light Adjustable Lens (LAL)
100. The generalized method 400 can comprise the following steps.
[0296] Causing 410 an LAL 100, implanted into an eye, to induce a
first depth of focus in an ophthalmic optical system, i.e. the
optical system of the eye with its cornea and the implanted LAL
100; [0297] Determining 420 a central region 110 and a
corresponding central axis 112 of the LAL 100; and [0298]
Illuminating 430 the LAL 100 with an illumination pattern 434
centered on the central axis 112 to induce a second depth of focus
the ophthalmic optical system; wherein [0299] (440) the central
axis 112 is laterally shifted relative to a LAL axis 102, and
[0300] (450) the second depth of focus is at least 0.5 diopters
greater than the first depth of focus.
[0301] Steps 420-450 can be analogous to the steps 230-260 of the
method 200, with appropriate modifications in the last step. In
addition, in some embodiments, the causing step 410 can include the
applying 220 of the first illumination 222 to the LAL 100, in
analogy to step 220 of the method 200. In other embodiments, the
causing step 410 can include providing a LAL 100 with a pre-molded
depth of focus, in analogy to step 310 of method 300. The
pre-molded depth of focus can be induced by a position-dependent
peripheral optical power 124 in the peripheral annulus 120,
centered on the annulus axis 122. Finally, in some embodiments the
causing step 410 may involve a combination of the steps 220 and
310.
[0302] As before, all aspects of the blended LALs 100 shown in
FIGS. 13-23, all aspects of the method 200 shown in FIGS. 24-27,
and all aspects of the method 300 shown in FIG. 28 can be combined
with embodiments of the method 400.
[0303] FIG. 30 illustrates a method 500 of adjusting the Light
Adjustable Lens (LAL) 100, primarily as shown in FIG. 22. The
method 500 can include the following steps. [0304] Implanting 510 a
LAL 100b, having a LAL axis 102b, into an eye; and [0305] Applying
520 an illumination 522 to the LAL 100b with an illumination
pattern 524 to induce a position-dependent adjusted optical power
314 in a light-adjusted region 310r, centered on an adjustment axis
312; wherein [0306] (530) the adjustment axis 312 is laterally
shifted relative to the LAL axis 102b.
[0307] As before, all aspects of the blended LALs 100 shown in
FIGS. 13-23, all aspects of the methods 200/300/400 shown in FIGS.
24-29 can be combined with embodiments of the method 500.
[0308] 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.
[0309] While this document contains many specifics, details and
numerical ranges, these should not be construed as limitations of
the scope of the invention and of the claims, but, rather, as
descriptions of features specific to particular embodiments of the
invention. Certain features that are described in this document in
the context of separate embodiments can also be implemented in
combination in a single embodiment. Conversely, various features
that are described in the context of a single embodiment can also
be implemented in multiple embodiments separately or in any
suitable subcombination. Moreover, although features may be
described above as acting in certain combinations and even
initially claimed as such, one or more features from a claimed
combination can in some cases be excised from the combination, and
the claimed combination may be directed to another subcombination
or a variation of a subcombinations.
REFERENCES
[0310] All patents and publications mentioned in the specification
are indicative of the level of those skilled in the art to which
the invention pertains. All patents and publications are herein
incorporated by reference in their entirety to the same extent as
if each individual publication was specifically and individually
indicated to be incorporated by reference.
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