U.S. patent application number 13/861533 was filed with the patent office on 2013-11-07 for eye treatment.
This patent application is currently assigned to Vision CRC Limited. The applicant listed for this patent is Vision CRC Limited. Invention is credited to Arthur Ho, Brien Anthony HOLDEN, Fabrice MANNS, Jean-Marie Arthur Parel.
Application Number | 20130297016 13/861533 |
Document ID | / |
Family ID | 38667328 |
Filed Date | 2013-11-07 |
United States Patent
Application |
20130297016 |
Kind Code |
A1 |
Ho; Arthur ; et al. |
November 7, 2013 |
EYE TREATMENT
Abstract
The present invention relates to a method of determining the IOL
refractive index for an ocular replacement material for replacing
tissue in the capsular bag comprising combining a neutral
(non-correcting) reference refractive index ("NRRI") of between
1.421 and 1.450 with a refractive index correction factor ("RICF")
ascertained by reference to the refractive power required to
correct the patient's refractive error. The present invention also
relates to methods of treating presbyopia, myopia and hyperopia
using the above method.
Inventors: |
Ho; Arthur; (Coogee, AU)
; HOLDEN; Brien Anthony; (Kensington, AU) ; MANNS;
Fabrice; (Palmetto Bay, FL) ; Parel; Jean-Marie
Arthur; (Miami Shores, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Vision CRC Limited; |
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US |
|
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Assignee: |
Vision CRC Limited
Kensington
AU
|
Family ID: |
38667328 |
Appl. No.: |
13/861533 |
Filed: |
April 12, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12299239 |
Oct 31, 2008 |
8439974 |
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PCT/AU07/00586 |
May 3, 2007 |
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13861533 |
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60796940 |
May 3, 2006 |
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Current U.S.
Class: |
623/6.11 |
Current CPC
Class: |
A61F 2/16 20130101; A61F
2240/002 20130101; A61F 2/1624 20130101; A61L 2430/16 20130101;
A61L 27/18 20130101; A61L 27/50 20130101; A61L 27/18 20130101; C08L
83/04 20130101 |
Class at
Publication: |
623/6.11 |
International
Class: |
A61F 2/16 20060101
A61F002/16 |
Claims
1-8. (canceled)
9. A method of treating presbyopia of a subject by replacing tissue
in the subject's capsular bag, comprising replacing the tissue in
the subject's capsular bag with an ocular replacement material
selected to have a refractive index equivalent to a neutral
reference refractive index, wherein the neutral reference
refractive index is between 1.426 and 1.442.
10. A method according to claim 9, wherein the ocular replacement
material is curable in situ.
11. A method according to claim 9, wherein the ocular replacement
material is shaped by the subject's capsular bag.
12. A method according to claim 9, in which the ocular replacement
material is a polymer cured in situ from a cross-linkable siloxane
macromonomer.
13. A method according to claim 10, wherein the neutral reference
refractive index is between 1.426 and 1.438.
14. A method according to claim 10, wherein the neutral reference
refractive index is 1.427.
15. A method of determining a refractive index for an ocular
replacement material for replacing tissue in the capsular bag of a
patient, comprising combining (i) a neutral reference refractive
index of between 1.426 and 1.442 with (ii) a refractive index
correction factor ascertained by reference to a refractive power
required to correct a refractive error of the patient, and (iii)
selecting an ocular replacement material, as an intraocular lens
(IOL), having the refractive index determined.
16. A method according to claim 15, wherein the ocular replacement
material is curable in situ.
17. A method according to claim 15, wherein the ocular replacement
material is shaped by the subject's capsular bag.
18. A method according to claim 15, in which the ocular replacement
material is a polymer cured in situ from a cross-linkable siloxane
macromonomer.
19. A method according to claim 16, wherein the neutral reference
refractive index is between 1.426 and 1.438.
20. A method according to claim 16, wherein the neutral reference
refractive index is 1.427.
21. An ocular replacement material selected by the method of claim
15.
22. An ocular replacement material selected by the method of claim
17.
Description
FIELD OF THE INVENTION
[0001] The invention relates to a new eye treatment including the
replacement of the lens of an eye with an artificial accommodating
intraocular lens. It can be used, for example, to treat
presbyopia.
BACKGROUND OF THE INVENTION
[0002] The human eye is a complex sensory organ. It includes a
cornea, or clear outer tissue which refracts light rays en route to
the pupil, an iris which controls the size of the pupil thus
regulating the amount of light entering the eye, and a lens which
focuses the incoming light through the vitreous to the retina. The
lens is often considered to have 3 portions, namely a nucleus, a
cortex around the nucleus and an outer capsular region. In the
adult lens, the nucleus tends to be harder and has a relatively
constant sectional refractive index, whereas the refractive index
of the cortex is known to exhibit a gradient. Any obstruction or
loss in clarity within these structures causes scattering or
absorption of light rays resulting in diminished vision.
[0003] With age, there is a loss of lens flexibility and/or lens
transparency. The natural flexibility of the lens is essential for
focusing light onto the retina by a process referred to as
accommodation. Accommodation is the process by which the eye
adjusts its focus for visual objects at different distances. A
common condition known as presbyopia results from diminished
flexibility of the lens thus reducing near vision acuity.
Presbyopia usually begins to occur in adults during their
mid-forties; conventionally, these near vision problems are
alleviated with glasses or contact lenses.
[0004] Another cause of diminished vision is cataracts which is
associated with a loss of lens transparency in the aging eye. Some
treatments involve the surgical removal of the natural lens. An
artificial lens is then needed to restore vision. Three types of
prosthetic lenses are available: cataract glasses, external contact
lenses, and IOLs. Cataract glasses have thick lenses, are
uncomfortably heavy, and cause vision artefacts such as central
image magnification and side vision distortion. Contact lenses
resolve many of the problems associated with glasses, but require
cleaning, are difficult to handle (especially for elderly patients
with symptoms of arthritis), and are not suited for persons who
have restricted tear production. More particularly, contact lens
for restoring vision after lens removal (called "aphakia") are
necessarily very thick due to the high power required. Such thick
contact lenses are uncomfortable and cannot deliver sufficient
oxygen to support long-term ocular health. IOLs are used in the
majority of cases to overcome the aforementioned difficulties
associated with cataract glasses and contact lenses.
[0005] Known IOLs include non-deformable, foldable and expansible
lenses, which may be formed from materials such as acrylics,
hydrogels or polysiloxanes. These IOLs are implanted by making an
incision in the cornea and inserting a preformed IOL. To treat
cataracts, the natural lens is removed before the IOL is implanted.
In some procedures, the capsule is left in place following lens
extraction. The IOL is then implanted inside the capsule via the
capsulorhexis; a hole typically of a few mm in diameter made at the
anterior capsule surface. The capsulorhexis is made to provide an
opening from which the content (cortex and nucleus) of the lens can
be removed during the procedure. To minimise trauma during
implantation, foldable and expansible IOLs have been developed.
These lenses may be rolled up and inserted through a small tube,
which allows a smaller incision to be made in the cornea as well as
a smaller diameter capsulorhexis to be made in the capsule. Smaller
incisions and rhexes provide quicker post-op recovery as well as
improved post-op visual outcomes due to less likelihood of
distortion of the cornea. For example, dehydrated hydrogels can be
used with these small incision techniques. Hydrogel lenses are
dehydrated before insertion and naturally rehydrate once inside the
capsular bag. To be suitable as IOLs, these deformable lenses
require not just appropriate optical properties, but also
mechanical properties, such as structural integrity and elasticity,
to permit them to deform during implantation and then regain their
shape in vivo. However, currently available IOLs are still
relatively much more rigid than the young, flexible natural lens.
Thus, such IOLs are not capable of accommodating when in vivo, and
so are not an optimal solution as they do not restore the near
vision capability (accommodation) of the natural young eye.
[0006] To further develop IOLs and reduce surgical incisions to
below 1.5 mm, techniques utilising injectable IOLs have been
suggested. Injectable IOLs would be implanted by lens filling (or
refilling) procedures, such as Phaco-Ersatz. In such a procedure
the natural crystalline material of the lens is extracted while the
lens capsule-zonule-ciliary body framework is maintained. The
intact lens capsule is then refilled by injecting a low viscosity
material into the empty capsular bag through a small diameter
capsulorhexis. The material may then be cured in situ. Injectable
IOLs use the capsular bag to form the shape of the lens. Provided
the elasticity of the refilling material is sufficiently low, the
lens shape can then be manipulated by the ciliary muscles and
zonules as occurs with the natural lens. Consequently, such
injectable IOLs are able to accommodate in viva By replacing the
hardened lens material of a presbyopic patient with a soft gel
injectable IOL the patient's ability to change focus, or
accommodate, can be restored.
[0007] Apart from problems with in situ curing, such as controlling
the crosslinking process and finding clinically acceptable
conditions, there has been a struggle to develop polyorganosiloxane
compositions for use as injectable IOLs. Injectable IOL materials
need to have a suitable viscosity for injection, a suitable
refractive index, suitable mechanical characteristics after curing,
i.e. modulus, good transparency, be biocompatible, including having
minimal extractables and be sterilisable.
[0008] The properties, such as viscosity, modulus and extractables,
differ from those required for deformable IOLs. Consequently,
materials useful in deformable IOLs are by no means suitable for
use as injectable IOLs. For example, polydimethylsiloxane (PDMS)
has been employed as a material in foldable or deformable IOLs. In
the injectable IOL context though, PDMS has been found to have a
relatively low viscosity and thereby a tendency to leak out of the
injection site (i.e. the capsular bag) before curing. To address
this deficiency, high viscosity polysiloxanes have been added to
the PDMS reaction mix. However, a drawback of high viscosity
silicones is that they can entrap air bubbles, which can impair the
optical quality of the resulting product. Also, they are difficult
for a surgeon physically to inject in a very delicate environment,
often requiring substantial force. In addition, it has been found
that polyorganosiloxanes having a high fraction of dimethylsiloxane
units may have an unacceptably low specific gravity with the
undesired result that the injected lens material will float on any
aqueous layer present in the capsular bag. In such a case, it will
be difficult to fill the capsular bag completely and will require
the surgeon to manually express intra-capsular water in order to
maintain the correct lens shape during the filling and curing
process.
[0009] Therefore, it is desirable to formulate processes for
replacing the natural lens with an accommodating IOL that provides
optimal results in vivo. Further, it is desirable to formulate
injectable lens forming materials from polysiloxanes that has a
suitable refractive index and the desired mechanical and optical
qualities so as to constitute an optimal replacement for the
natural lens.
[0010] Reference to any prior art in the specification is not, and
should not be taken as, an acknowledgment or any form of suggestion
that this prior art forms part of the common general knowledge in
Australia or any other jurisdiction or that this prior art could
reasonably be expected to be ascertained, understood and regarded
as relevant by a person skilled in the art.
[0011] As used herein, the term "comprise" and variations of the
term, such as "comprising", "comprises" and "comprised", are not
intended to exclude other additives, components, integers or
steps.
SUMMARY OF THE INVENTION
[0012] When conducting experiments to refill the natural lens with
a soft gel, it was surprisingly found that in non-human primates
(rhesus) the replacement induced a refractive error (hyperopia) in
all animals. Similar results were obtained for experiments
conducted with ex vivo human eyes. It was expected that if the
contents of the natural lens is replaced with a polymer of the same
refractive index (RI) no refractive error would be induced.
Conventional optical measurements and modelling provide `text-book`
values for the average refractive index of the natural human lens
as being between 1.40 and 1.42.
[0013] It has been discovered that, if the lens of an eye is
evacuated and the capsular bag refilled with polymers with
refractive index in the `text-book` range for the eye, such as
dimethyl siloxanes having an RI of 1.407, the resulting power-load
and power-stretch curves show not only an induced refractive change
in the eye, but also a departure from the accommodative response
(change in power with ciliary muscle effort and change in power
with change in lens diameter) of a natural lens. In contrast, when
higher refractive index materials are used to refill the lens
capsular bag (e.g. RI of 1.4457), the refilled lens very closely
mimics the static refractive state and the accommodative response
of the natural lens.
[0014] Accordingly, the RI of a material for refilling the lens
without resulting in a departure from the lens' original optical
power has surprisingly been found to be higher than expected, being
between 1.421 and 1.450. The RI of a material for refilling the
lens of rhesus primates and maintaining its optical power is
preferably between 1.426 and 1.444, more preferably between 1.435
and 1.444 and most preferably about 1.440. For humans generally,
the RI of a material for refilling the lens without introducing a
change in power is typically greater than 1.421 and less than about
1.442. More usually, it is between 1.426 and 1.438. In one
embodiment, it is about 1.427. For humans over the age of 40, the
RI of a material for refilling the lens without introducing a
change in power is typically greater than 1.426 and less than about
1.442. More usually, it is between 1.426 and 1.438. In one
embodiment, it is about 1.427.
[0015] Consequently, in one aspect, the present invention provides
a method of determining the IOL refractive index for an ocular
replacement material for replacing tissue in the capsular bag
comprising combining a neutral (non-correcting) reference
refractive index ("NRRI") of between 1.421 and 1.450 with a
refractive index correction factor ("RICF") ascertained by
reference to the refractive power required to correct the patient's
refractive error (i.e. long-sightedness or short-sightedness). The
NRRI has surprisingly been found to be different for rhesus
primates and humans, despite other substantial similarities which
have led to the rhesus eye being a widely accepted model for the
human eye. In this specification, some of the data is based on
rhesus eyes, where the NRRI is assessed to be between 1.426 and
1.444, more likely 1.435 and 1.444 and likely to be about 1.440.
The NRRI for humans generally is assessed to be between 1.421 and
1.442, more likely between 1.426 and 1.438 and likely to be about
1.427. The NRRI for humans over the age of 40 is assessed to be
between 1.426 and 1.442, more likely between 1.426 and 1.438 and
likely to be about 1.427.
[0016] The refractive power required may be assessed in known ways
by optometric examination. The related RICF may be calculated in
known ways using suitable formulae.
[0017] By adjusting the refractive index of the polymer used to
refill the lens capsular bag, one can correct refractive errors
(such as myopia and hyperopia). This involves measuring the
patient's refractive state and prescribing a material with the
correct IOL refractive index to `neutralise` the refractive
condition.
[0018] Further, by replacing the hardened material of a presbyopic
natural lens with a soft gel having a correct NRRI, accommodation
may be restored to a subject suffering presbyopia.
[0019] Accordingly, another aspect of the present invention is a
method of treating presbyopia of a subject by replacing tissue in
the subject's capsular bag comprising the steps of: [0020] (a)
obtaining an ocular replacement material having a refractive index
equivalent to a neutral (non-correcting) reference refractive index
of between 1.421 and 1.450; and [0021] (b) replacing the tissue in
the subject's capsular bag with the ocular replacement
material.
[0022] In step (a), the NRRI is preferably between 1.426 and 1.444
for rhesus primates, more preferably between 1.435 and 1.444, and
most preferably about 1.440. For humans generally, the NRRI is
desirably between 1.421 and 1.442. More usually it is between 1.426
and 1.438. In one embodiment, it is about 1.427. For humans over
the age of 40, the NRRI is desirably between 1.426 and 1.442. More
usually it is between 1.426 and 1.438. In one embodiment, it is
about 1.427.
[0023] A further aspect of the present invention provides a method
of treating myopia, hyperopia, or presbyopia of a subject by
replacing tissue in the subject's capsular bag comprising the steps
of: [0024] (a) calculating a refractive index correction factor
based on an estimate of the refractive power correction required,
if any, derived by measurement and/or examination of the subject's
eye; [0025] (b) determining the sum of the refractive index
correction factor of step (a) if any with a neutral
(non-correcting) reference refractive index of between 1.421 and
1.450; [0026] (c) obtaining an ocular replacement material having a
refractive index of the sum determined in step (b); and [0027] (d)
replacing the tissue in the subject's capsular bag with the ocular
replacement material.
[0028] In step (b), the NRRI is preferably between 1.426 and 1.444
for rhesus primates, more preferably between 1.435 and 1.444, and
most preferably about 1.440. For humans generally, the NRRI is
desirably between 1.421 and 1.442. More usually it is between 1.426
and 1.438. In one embodiment, it is about 1.427. For humans over
the age of 40, the NRRI is desirably between 1.426 and 1.442. More
usually it is between 1.426 and 1.438. In one embodiment, it is
about 1.427.
[0029] Preferably the ocular replacement material of step (c) is an
ocular replacement material for replacing tissue in the capsular
bag having suitable properties for an accommodating lens. In one
embodiment, the ocular replacement material is a siloxane polymer,
such as one formed in situ from a cross-linkable siloxane
macromonomer. The polymer is desirably polymerisable in situ in the
capsular bag. Suitable ocular replacement materials include the
polymers described in this specification and co-pending PCT
application entitled "Biological polysiloxanes" by Dr T C Hughes et
al filed on the same date as this specification and claiming
priority from U.S. provisional patent No. 60/796,936.
[0030] The material will have a predetermined refractive index
calculated to be the sum of (i) the NRRI for rhesus primates,
humans generally or humans over the age of 40, as described above,
and (ii) a predetermined RICF ascertained by reference to the
refractive power required to correct the refractive error. The RICF
may be zero e.g. for the case of an emmetropic eye (i.e. an eye not
requiring any refractive correction). In preferred embodiments, the
predetermined refractive index of the material may be 1.421-1.422,
1.422-1.423, 1.423-1.424, 1.424-1.425, 1.425-1.426, 1.426-1.427,
1.427-1.428, 1.428-1.429, 1.429-1.430, 1.430-1.431, 1.431-1.432,
1.432-1.433, 1.433-1.434, 1.434-1.435, 1.435-1.436, 1.436-1.437,
1.437-1.438, 1.438-1.439, 1.439-1.440, 1.440-1.441, 1.441-1.442,
1.442-1.443, 1.443-1.444, 1.444-1.445, 1.445-1.446, 1.446-1.447,
1.447-1.448, 1.448-1.449 or 1.449-1.450.
[0031] In one embodiment, the refractive index of the ocular
replacement material is 1.440 when the RICF is 0 (ie an NRRI of
1.440) for rhesus primates, and 1.427 for humans.
[0032] Preferably, when treating myopia or hyperopia the ocular
replacement material used in step (e) results in an accommodating
IOL.
[0033] In yet a further aspect, the present invention provides an
ocular replacement material for replacing tissue in a subject's
capsular bag having a refractive index of the sum of: (a) a neutral
(non-correcting) reference refractive index of between 1.421 and
1.450; and (b) a refractive index correction factor ascertained by
reference to the refractive power required to correct the subject's
refractive error, if any.
[0034] In a further aspect, the present invention provides an
accommodating IOL for replacing tissue in a subject's capsular bag
comprising the above described ocular replacement material.
[0035] Further, the invention provides a method of producing an
ocular replacement material for a subject having ametropia (i.e. a
refractive error such as myopia or hyperopia) or presbyopia
comprising: [0036] (a) calculating a refractive index correction
factor based on an estimate of the refractive power correction
required, if any, derived by measurement and/or examination of a
subject's eye; [0037] (b) determining the sum of the refractive
index correction factor of step (a) if any with a neutral
(non-correcting) reference refractive index of between 1.421 and
1.450; and [0038] (c) producing an ocular replacement material
having a refractive index of the sum determined in step (b).
[0039] The invention also comprises a method of implanting an
accommodating IOL comprising introducing an ocular replacement
material having a refractive index of the sum of: (a) a neutral
(non-correcting) reference refractive index of between 1.421 and
1.450; and (b) a refractive index correction factor ascertained by
reference to refractive power required to correct a refractive
error into a capsular bag of a subject.
[0040] Preferably, the ocular replacement material is curable and
the method further comprises the step of curing the ocular
replacement material after introducing the ocular replacement
material into the capsular bag.
[0041] Another aspect of the present invention is the use of an
ocular replacement material for replacing tissue in a subject's
capsular bag having a refractive index of the sum of: (a) a neutral
(non-correcting) reference refractive index of between 1.421 and
1.450; and (b) a refractive index correction factor ascertained by
reference to refractive power required to correct a refractive
error, for the manufacture of an accommodating intraocular lens for
use in treating myopia, hyperopia or presbyopia.
[0042] The ocular replacement material of the present invention is
preferably a macromonomer having a viscosity before curing of
between 1,000 and 150,000 cSt, preferably 1,000 to 80,000 cSt and
more preferably 1,000 to 60,000 cSt. Preferably, the ocular
replacement material of the present invention is curable into a
polymeric material having a modulus at 37.degree. C. of less than
50 kPa, preferably less than 10 kPa and more preferably less than 5
kPa.
[0043] In preferred embodiments of the invention, the ocular
replacement material is a siloxane macromonomer.
[0044] To better illustrate the invention, the invention will now
be described with reference to particular embodiments and examples,
which do not limit the scope of the invention described.
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] In the accompanying figures,
[0046] FIG. 1 is a graph of spherical equivalence (i.e. the
spherical power component from a measurement of the refractive
state of an eye) against time for control and experimental eyes of
a NHP (rhesus) subject containing their natural lenses, that is
before evacuation and refilling of the experimental eye.
[0047] FIG. 2 is a graph of spherical equivalence against time for
control and experimental eyes of the NHP (rhesus) subject of FIG. 1
seven days after the lens of the experimental eye was evacuated and
refilled with a polydimethylsiloxane (PDMS) based polymeric
material having an RI of 1.407.
[0048] FIG. 3 is a graph of power (D) against load (g) resulting
from EVAS testing on an eye containing first its natural lens
(natural), second, the lens refilled with uncured PDMS based
polymeric material having a refractive index of 1.405 (uncured) and
third the lens after the PDMS based material is cured (cured).
[0049] FIG. 4 is a graph of hyperopic shift (D) of various
experimental lenses that had been evacuated and refilled with PDMS
based polymeric material having a refractive index of 1.405 against
the power in dioptres for the initial natural lens measured during
EVAS testing.
[0050] FIG. 5 is a graph of power (D) against load (g) resulting
from EVAS testing on an eye containing first its natural lens
(natural), second, the lens refilled with uncured siloxane macromer
having a refractive index of 1.4457 (uncured) and third the lens
after the siloxane macromer is cured (cured).
[0051] FIG. 6 is a graph relating the refractive index correction
factor to the refractive power correction required for one
exemplary model.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0052] In testing the efficacy of a soft gel for use as an
injectable IOL, the inventors conducted experiments on non-human
primates (NHP) (rhesus). In these experiments, each subject had the
lens of its right eye evacuated and refilled with a soft gel made
from a PDMS based polymeric material having an RI of 1.407. The
power and amplitude of accommodation of the left, natural lens and
right, refilled experimental lens of each subject was then compared
at various intervals post-operatively. The amplitude of
accommodation of the lenses was tested pharmacologically. In short,
subconjunctival administration of pilocarpine induces the eye to
accommodate to its near focus, increasing the power of the eye.
Refractometry (for measuring the refractive state of the eye),
using an auto-refractor, was carried out on each eye before and
after pilocarpine administration. The difference in the refractive
state of an eye before and after administration of pilocarpine
indicates the amplitude of accommodation achieved by the lens.
[0053] FIG. 1, which is a graph of spherical equivalence against
time, shows a comparison of the left (control) and right
(experimental) eyes of one NHP subject before the right lens was
evacuated and refilled. The spherical equivalence is the mean power
of the eye when averaging out the presence of any astigmatism. The
control eye is the plot that starts at a marginally higher
spherical equivalent at the earliest time (10:40), and the line
that starts marginally lower is the experimental eye. The vertical
broken lines indicate the times at which pilocarpine is
administered to the eyes, inducing accommodation and an increase in
power. The increase in power in the eye due to accommodation
translates to an apparent myopic-shift of the eye's refractive
state. Hence, the spherical equivalence value decreases with
increasing amount of accommodation. The two plots are effectively
superimposed, which indicates that the refractive state of both the
control and experimental eyes containing their natural lenses was
consistent before pilocarpine administration. Further, the
administration of pilocarpine to the eyes at approximately 10:47
and 11:00 induced similar changes in the refractive state, which
indicates that the amplitude of accommodation of each of the eyes
were also consistent.
[0054] FIG. 2 shows the response to pilocarpine administration of
the control and experimental eyes of the subject of FIG. 1 seven
days after evacuation of the lens capsular bag of the experimental
eye and injection of a PDMS based polymeric material having an RI
of 1.407 to form an accommodating IOL. The upper line represents
the experimental eye containing the IOL and the lower line
represents the control eye having the natural lens. Again, the
vertical broken lines indicate the times at which pilocarpine was
administered. The resting (unaccommodated) refraction of the
control and experimental eyes of the subject were quite different.
The experimental eye has about +6 D higher refraction than the
control eye. This indicates that refilling of the lens with the
PDMS based polymeric material induces a hyperopic shift of
approximately 6 D which means that the experimental eye has less
power than the control eye.
[0055] The inventors discovered that each of the subjects
consistently experienced a hyperopic shift in the refilled
experimental eye, which indicates that the PDMS based polymeric
lens did not provide sufficient power to restore the lens to its
natural power.
[0056] Regarding amplitude of accommodation, as shown in FIG. 2,
the overall change in the refractive power of the experimental eye
following administration of pilocarpine indicates that the refilled
lens is capable of accommodating. However, the results from
experiments on each of the subjects showed a median relative
amplitude of accommodation of only about 60% of that of the control
eyes. Accordingly, the amplitude of accommodation achievable by the
PDMS based polymeric lens is less than that of the natural
lens.
[0057] The differences in power and accommodation discovered by the
inventors were confirmed using an ex vivo accommodation simulator
(EVAS). This machine simulates accommodation using ex vivo lenses.
EVAS uses the intact ciliary body and zonules of the cadaver eyes
to manipulate the shape of the cadaver lenses, so that
accommodation is achieved in the same manner as for a live eye.
During manipulation or stretching, the forces on the lens, the
refractive power of the lens and the lens diameter (related to the
amount of lens stretching) can be simultaneously measured. When a
cadaver eye is placed in the EVAS, the power-stretch or power-load
curves of the natural lens can be measured. The lens capsular bag
can then be evacuated and refilled by injecting suitable
macromonomers and remeasured. The macromonomers in the capsular bag
can then be cured by photopolymerisation and the power of the cured
refilled lens also measured. EVAS tests were conducted on both
human and NHP (rhesus) cadaver eyes.
[0058] Various NHP (rhesus) and human eyes were tested using the
EVAS by measuring the change in power obtained from the lens of the
eye as a factor of the increase in load applied to the lens. For
each eye, the measurements were taken for the natural lens, the
lens capsular bag refilled by an uncured PDMS based polymeric
material having an RI of approximately 1.41 and the lens after the
PDMS based polymeric material was cured. These tests showed the
rate of change of lens power (accommodation or disaccommodation)
given a change in the amount of muscular force exerted by the
ciliary body and zonules.
[0059] The results for a rhesus lens refilled by an uncured PDMS
based polymeric material having an RI of 1.405 are given in FIG. 3.
The graph shows the work (load) required by the ciliary
body/zonules of the eye in order to change the power of each type
of lens.
[0060] It also shows the difference in power and accommodation
resulting from the refilling of the lens capsule. The right-hand
extremity of the results (towards a load of 8 g) is analogous to
the maximum disaccommodated state of the lens. This represents the
resting (unaccommodated) refractive state of the lens. The vertical
displacement of the plots at 8 g load shows that the refilled lens
(when cured and uncured) has less power than the natural lens at
distance focus by approximately 13 D, indicating a hyperopic shift
has been induced by refilling. The refilled lens has less power
(i.e. is relatively hyperopic) than the natural lens at all loads.
The gradients of the lines in FIG. 3 indicate the rate of
accommodation of the lens for the same rate of change of ciliary
body/zonules load. The gradients of the refilled lenses (-1.55 D/g
and -1.53 D/g uncured and cured respectively) are less than that
for the natural lens (-2.09 D/g), indicating that the amplitudes of
accommodation of the refilled lenses were less than that of the
natural lens. These results are consistent with the NHP trials.
[0061] In addition, the EVAS tests indicated that the results of
the NHP (rhesus) trials and tests provide a reasonable predictor
for application to the human lens. The graph in FIG. 4 shows an
approximately linear relationship between the amount of hyperopic
shift attributable to an experimental lens and the power of the
initial natural lens. This almost direct correlation between
natural lens power and hyperopic shift allows reasonable
experimental extrapolation of these principles to humans.
[0062] This surprising discovery of an error in the power and
amplitude of accommodation of a refilled lens could be attributable
to any number of factors including the lens shape, which may be
affected by over or under-filling the lens, the post-op corneal
shape, the modulus of the PDMS based polymeric material, the
refractive index of the PDMS based polymeric material, pupil size
and the lack of a gradient refractive index across the refilled
lens.
[0063] Without being bound by any theory or mode of action, the
cause of the refractive error seen in the primate and EVAS
experiments is hypothesised to be due to a mismatch of the
refractive index of the PDMS based material, which was
approximately 1.41, and the equivalent refractive index required to
restore the optical properties (power and accommodation) of the
lens to its natural state. This hypothesis is supported by the
inventors' discovery that use of a polymeric material having a
higher refractive index of 1.4457 produced a lens having similar
power and amplitude of accommodation to that of a natural lens. The
results of EVAS trials using the higher RI polymeric material are
shown in FIG. 5. In this trial an NHP (rhesus) lens was used and
measurements were taken for the natural lens, the lens capsular bag
refilled by an uncured siloxane based polymeric material having an
RI of 1.4457 and the lens after the siloxane based polymeric
material was cured. The power of the refilled lens at both distance
focus (4 g load) and near focus (0 g load) is approximately
equivalent to the power of the natural lens, indicating the higher
RI material effectively eliminated the hyperopic shift previously
seen in the NHP and EVAS studies using the lower RI materials.
Further, the similar gradients of the three plots indicate that the
natural, uncured and cured lenses all have similar amplitudes of
accommodation.
[0064] These results indicate that the refractive index required to
restore the power and accommodation amplitude of the lens to its
natural state is higher than would be predicted from what is
traditionally thought to be the equivalent refractive index of the
lens.
[0065] Accordingly, the inventors have surprisingly found the NRRI
to be between 1.421 and 1.450. The NRRI for rhesus primates is
assessed to be between 1.426 and 1.444, more likely 1.435 and 1.444
and likely to be about 1.440. The NRRI for humans generally is
assessed to be between 1.421 and 1.442, more likely between 1.426
and 1.438 and likely to be about 1.427. The NRRI for humans over
the age of 40 is assessed to be between 1.426 and 1.442, more
likely between 1.426 and 1.438 and likely to be about 1.427. These
NRRI values may advantageously be used in methods of the present
invention for preparing materials for accommodating IOLs that are
suitable for use in humans or rhesus primates.
[0066] For instance, the NRRI may be used in a method of
determining the IOL refractive index for an ocular replacement
material for replacing tissue in the capsular bag comprising
combining a neutral (non-correcting) reference refractive index of
between 1.421 and 1.450 with a refractive index correction factor
ascertained by reference to the refractive power required to
correct a patient's refractive error.
[0067] The refractive power required may be assessed in known ways
by optometric examination. For instance, the distance refractive
state of a patient may be assessed using conventional methods of
refraction, such as subjective refraction (employing e.g. a letter
chart and trial frame and trial-lenses of various powers) or an
objective refraction, such as retinoscopy, or a more modern
auto-refractometer. The near refractive state may be assessed using
a near-point chart, or dynamic retinoscopy.
[0068] The related RICF may be calculated in known ways using
suitable formulae. For instance, various models may be assumed in
order to calculate an RICF from the measured refractive error. One
possible model is shown in FIG. 6. It will be understood that any
one of a number of different eye models could be used as a basis
for calculating the relationship between RICF and refractive error.
Further, it will be understood that variation in models would
result in slightly different relationships being calculated.
[0069] While interpolation of graphs such as that shown in FIG. 6
may be tedious and imprecise in the clinical setting, an
approximate rule for calculating RICF based on the same model as
shown in FIG. 6 can be defined whereby:
For Myopes: RICF=RX.times.0.00632
For Hyperopes: RICF=RX.times.0.00578 [0070] where RX is the
refractive error to correct in dioptres (D).
[0071] As the RICF does not have a linear relationship with
refractive error, the rules for myopes and hyperopes differ to
afford greater precision.
[0072] When used in methods of treating presbyopia, myopia or
hyperopia, the ocular replacement material may be introduced into
the eye using a lens refilling operation, which is similar many
respects to a current cataract extraction and IOL implantation
procedure (e.g. extra-capsular extraction procedure). It would be
understood how to introduce the material to the eye. For instance,
a small corneal incision and a small capsulorhexis are made,
through which the lens core (including the cortex and nucleus) are
extracted. An ocular replacement material is injected into the
intact lens capsule using a fine gauge (e.g. 29-G or finer) cannula
and syringe to reform the lens.
[0073] Optionally, the ocular replacement material may then be
cured, such as by exposure to visible or UV light.
[0074] The material used to form the injectable IOL of FIG. 5 was a
macromonomer of the structural formula 1
##STR00001##
wherein a is 79.1 mol %, b is 20.6 mol % and c is 0.26 mol %. The
macromonomer had the following characteristics:
TABLE-US-00001 Mw (gpc) 27120 RI (@ 37.degree. C.) 1.4457 Viscosity
8290 cSt Mn 18274 PD 1.484
[0075] The macromonomer of Formula 1 may be synthesised by any
suitable method known in the art.
[0076] An advantageous method by which the phenyl and methacrylate
groups are attached to a siloxane macromonomer is by a
hydrosilylation reaction. For instance, using hydrosilylation on a
macromonomer that has tri-methyl substituted terminal silicons, the
phenyl and methacrylate groups are attached to the siloxane
backbone using the allyl-precursors, allyl benzene and
allyl-methacrylate, in methods known to those skilled in the art.
Scheme 1 illustrates a hydrosilylation reaction.
##STR00002##
[0077] The addition of the phenyl and methacrylate groups using
hydrosilylation reactions may be either to macromonomers, which are
silane functionalized, or to silane functionalized cyclic siloxane
intermediates before they are subjected to ring opening
polymerisation to form the macromonomer. Suitable cyclic siloxane
intermediates include tetramethylcyclotetrasiloxane
(D.sub.4.sup.H), trimethylcyclotrisiloxane (D.sub.3.sup.H),
pentamethylcyclopentasiloxane (D.sub.5.sup.H) or
hexamethyl-cyclohexasiloxane (D.sub.6.sup.H).
[0078] In the following schemes, where figures such as "a=80, b=20"
are provided, these are mol % values for the substituents
indicated, and do not necessarily correspond with a, b and c of
Formula 1.
[0079] One approach is to prepare silane functionalised
macromonomer with sufficient silane functionality to allow
introduction of both the phenyl groups and the methacrylate groups.
For instance, a silane functionalised macromonomer can be
sequentially functionalized as depicted in scheme 2.
##STR00003##
[0080] Alternatively, a cyclic intermediate monomer is first
functionalised with phenyl or methacrylate groups and then
subjected to ring opening polymerisation. Scheme 3 shows the
synthesis of allyl benzene and allyl methylacrylate functionalised
D.sub.4.sup.H, which would then by subject to ring opening
polymerisation.
##STR00004##
[0081] Using the materials and methods of the present invention, a
material with a higher (or lower) refractive index may be produced
in order to induce a refractive power change in a patient's eye in
order to correct a refractive error (resulting in emmetropia) and
at the same time produce a gel having a sufficiently low modulus,
as described herein, to allow accommodation in vivo. An IOL with
increased RI according to the invention as described above can have
an NRRI so that there is no shift in an experiment such as
illustrated in FIG. 4 for a normal eye. Adjustments can then be
made as required in preparing the material for the IOL. For a
human, an NRRI of about 1.427 would be used as a starting point,
and then adjusted or tuned as required.
[0082] The following examples, which illustrate how the methods of
the present invention may be implemented, are not limiting on the
scope of the invention.
EXAMPLES
Example 1
[0083] A 47 year old patient presents to an eye-care practitioner
(e.g. an ophthalmologist) complaining of difficulty with reading
and other near visual tasks, such as threading a needle. The
distance refractive state of the patient is measured using
conventional methods of refraction, such as subjective refraction
(employing e.g. a letter chart and trial frame and trial-lenses of
various powers) or an objective refraction, such as retinoscopy, or
a more modern auto-refractometer as understood by eye-care
practitioners. It is found that the patient is emmetropic (i.e.
does not require a visual correction to see clearly at distance).
However, on near refraction (for example, using a near-point chart,
or dynamic retinoscopy), it is found that the patient is
experiencing the near vision problems of an early presbyope,
resulting from the hardening crystalline lens. In order to treat
the presbyopia the patient undergoes a lens refilling operation in
order to re-establish a lens (an IOL) which will restore the
patient's ability to accommodate.
[0084] The lens refilling operation in many respects is identical
to a current cataract extraction and IOL implantation procedure
(e.g. extra-capsular extraction procedure) with some minor but
crucial differences. Hence, the entire procedure is not described
in detail as it parallels a procedure currently carried out
frequently by ophthalmic surgeons. The differences are described so
that technical details may be more fully appreciated.
[0085] A small corneal incision is made at the para-limbal region
to provide access to the anterior segment. Following dilation of
the pupil using a pharmacological agent such as atropine or
cyclopentolate, a small capsulorhexis (around 1 mm or less in
diameter) is made manually at the periphery of the anterior capsule
using fine clawed forceps. Through the small corneal incision and
peripheral mini-capsulorhexis, the lens core (including the cortex
and nucleus) are extracted. This is carried out using any of a
number of implements familiar to ophthalmic surgeons, such as
aspirators or small-diameter tipped phaco-probes.
[0086] A gel suitable for refilling the capsular bag comprising the
macromonomer of Formula 1 is selected which has a refractive index
of 1.427, equivalent to the NRRI. This refractive index is the
preferred refractive index for this patient as no RICF is required
(the patient being emmetropic).
[0087] The gel, which includes a benzoin photinitiator, is injected
into the intact lens capsule using a fine gauge (e.g. 27-G or
finer) cannula and syringe to reform the lens. The gel is then
cured by exposure to light in the visible spectrum. The cured
polymer has a modulus of about 5 kPa. Consequently, the
still-intact ciliary muscle/ciliary body and zonules of the
accommodative apparatus can modify the shape of the injected IOL,
thereby restoring accommodation to the patient.
Example 2
[0088] Following refraction assessment as described above, it is
found that a 62 year old patient has +7.00 D of hyperopia.
Following slit-lamp biomicroscopic examination, it is observed that
the patient also has cataractous changes in the lens which are
affecting her vision. Due to the age of the patient, it is deduced
that her accommodative amplitude would be very low, being less than
about 1 D of accommodation. Given the cataractous and advanced
presbyopic state of the lens, a lens refilling operation is
conducted to replace the cataractous lens with a clear IOL, to
restore accommodation to the lens by using a material with a
suitable modulus and to correct the hyperopia by selecting a
material having an appropriate refractive index.
[0089] The refractive index of the material for use in the
injectable IOL is calculated in accordance with the present
invention. First, an NRRI of 1.427 is selected. Next, the RICF is
determined. By referencing the graph of FIG. 6, it can be seen that
for a hyperope of +7 D, the RICF is 0.0407. Adding the NRRI and
RICF gives a final preferred refractive index for the material of
the IOL of 1.468.
[0090] Alternatively, applying the rule for hyperopia derived from
FIG. 6 and described earlier, the +7 D hyperopia requires an RICF
of 0.0405, resulting in a final preferred refractive index for the
material of the IOL of 1.467.
[0091] Consequently, a gel suitable for refilling the capsular bag
comprising a macromonomer similar to the macromonomer of Formula 1
is selected, which has a refractive index of 1.468.
[0092] The gel is injected to form an accommodative IOL using the
method described in Example 1. However, a mini-capsulorhexis valve
is applied to the capsulorhexis prior to injection of the gel in
order to prevent leakage of the uncured macromonomer into the
anterior chamber. Following injection and light curing of the
polymer gel, the retaining arms of the valve are cut and removed
using surgical scissors in order to prevent iris irritation and
possibly a subsequent inflammation resulting in an iritis.
[0093] It will be understood that the invention disclosed and
defined in this specification extends to all alternative
combinations of two or more of the individual features mentioned or
evident from the text or drawings. All of these different
combinations constitute various alternative aspects of the
invention.
* * * * *