U.S. patent application number 12/685850 was filed with the patent office on 2010-05-06 for lenticular refractive surgery of presbyopia, other refractive errors, and cataract retardation.
This patent application is currently assigned to Second Sight Laser Technologies, Inc.. Invention is credited to Ronald Krueger, Raymond I. Myers.
Application Number | 20100114079 12/685850 |
Document ID | / |
Family ID | 46300638 |
Filed Date | 2010-05-06 |
United States Patent
Application |
20100114079 |
Kind Code |
A1 |
Myers; Raymond I. ; et
al. |
May 6, 2010 |
LENTICULAR REFRACTIVE SURGERY OF PRESBYOPIA, OTHER REFRACTIVE
ERRORS, AND CATARACT RETARDATION
Abstract
Methods for the creation of microspheres treat the clear, intact
crystalline lens of the eye with energy pulses, such as from
lasers, for the purpose of correcting presbyopia, other refractive
errors, and for the retardation and prevention of cataracts.
Microsphere formation in non-contiguous patterns or in contiguous
volumes works to change the flexure, mass, or shape of the
crystalline lens in order to maintain or reestablish the focus of
light passing through the ocular lens onto the macular area, and to
maintain or reestablish fluid transport within the ocular lens.
Inventors: |
Myers; Raymond I.;
(Collinsville, IL) ; Krueger; Ronald; (Cleveland,
OH) |
Correspondence
Address: |
BRINKS HOFER GILSON & LIONE
P.O. BOX 10395
CHICAGO
IL
60610
US
|
Assignee: |
Second Sight Laser Technologies,
Inc.
|
Family ID: |
46300638 |
Appl. No.: |
12/685850 |
Filed: |
January 12, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10750789 |
Jan 2, 2004 |
7655002 |
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12685850 |
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09897585 |
Jun 29, 2001 |
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10750789 |
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09312518 |
May 14, 1999 |
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09897585 |
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08821903 |
Mar 21, 1997 |
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09312518 |
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60036904 |
Feb 5, 1997 |
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60013791 |
Mar 21, 1996 |
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Current U.S.
Class: |
606/5 |
Current CPC
Class: |
A61F 2009/00872
20130101; A61F 9/009 20130101; A61F 9/008 20130101; A61F 9/00838
20130101; A61F 9/00804 20130101; A61F 2009/00887 20130101; A61F
2009/00897 20130101; A61F 9/00736 20130101; A61F 2009/00895
20130101; A61F 2009/0087 20130101 |
Class at
Publication: |
606/5 |
International
Class: |
A61F 9/008 20060101
A61F009/008; A61B 18/20 20060101 A61B018/20 |
Claims
1. A method for increasing the flexibility of an ocular lens of an
eye, comprising: a) selecting a location within an ocular lens of
an eye; b) creating a microsphere at the selected location, wherein
said microsphere comprises a gas-filled bubble of generally
spherical shape; and c) repeating processes a) and b) of selecting
and creating at a plurality of locations within said ocular lens so
as to increase flexibility of said ocular lens, wherein said
microsphere created in one process b) of creating remains separate
from any other microsphere created during another process b) of
creating.
2. The method of claim 1 wherein said increase in flexibility
corrects an optical anomaly of said eye.
3. The method of claim 2 wherein said optical anomaly comprises a
refractive error.
4. The method of claim 3 wherein said refractive error is selected
from the group consisting of: myopia, hyperopia, presbyopia,
regular astigmatism, irregular astigmatism, and aberrations.
5. The method of claim 4, wherein said repeating generates at least
one change in said ocular lens resulting in at least one effect
selected from the group consisting of: alteration of lens surface
curvature, increased lens flexibility, increased accommodation,
reduced light scatter, reduced rate of increase in light scatter,
and reduced rate of loss of accommodation.
6. The method of claim 1 wherein said increase in flexibility
increases accommodation of said ocular lens.
7. The method of claim 1 further including: allowing said
microsphere and said any other microsphere to collapse while
maintaining said increase in flexibility.
8. The method of claim 7 wherein said collapse decreases an
anterior to posterior thickness of said ocular lens.
9. The method of claim 1 wherein said increase in flexibility
creates no significant change in an anterior to posterior thickness
of said ocular lens.
10. (canceled)
11. The method of claim 1 wherein said microsphere and said any
other microsphere are created with a separation in a range of about
2 .mu.m to about 20 .mu.m.
12-14. (canceled)
15. The method of claim 1, further comprising: presenting
antioxidants to said eye.
16. The method of claim 15 wherein said antioxidants mediate
changes to said ocular lens or other ocular structures and
contents.
17. The method of claim 1, further comprising altering a lens
capsule of said ocular lens.
18. The method of claim 17, whereby a surface area of said lens
capsule is reduced by thermoplasty.
19. The method of claim 1, wherein said selecting primarily
includes selecting locations within adult and juvenile nuclei of
said eye.
20-36. (canceled)
37. The method of claim 4 wherein said refractive error is
myopia.
38. The method of claim 4 wherein said refractive error is
hyperopia.
39. The method of claim 4 wherein said refractive error is
presbyopia.
40. The method of claim 4 wherein said refractive error is regular
astigmatism.
41. The method of claim 4 wherein said refractive error is
irregular astigmatism.
42. The method of claim 4 wherein said refractive error is
aberrations.
43. The method of claim 5, wherein said at least one effect is
alteration of lens surface curvature.
44. The method of claim 5, wherein said at least one effect is
increased lens flexibility.
45. The method of claim 5, wherein said at least one effect is
increased accommodation.
46. The method of claim 5, wherein said at least one effect is
reduced light scatter.
47. The method of claim 5, wherein said at least one effect is
reduced rate of increase in light scatter.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The application claims benefit to and is a
Continuation-in-Part of U.S. patent application Ser. No. 09/897,585
filed Jun. 29, 2001, now abandoned, which is a Continuation of U.S.
patent application Ser. No. 09/312,518, filed May 14, 1999, now
abandoned, which in turn is a Continuation of U.S. patent
application Ser. No. 08/821,903, filed Mar. 21, 1997, now
abandoned, which claims priority to U.S. Provisional Application
No. 60/036,904, filed Feb. 5, 1997, and U.S. Provisional
Application No. 60/013,791, filed Mar. 21, 1996.
BACKGROUND
[0002] 1. Field of Invention
[0003] The invention comprises the use of electromagnetic energy to
make physical and biochemical alterations to the ocular lens of a
mammalian eye for the correction of visual impairments,
particularly presbyopia and including other ametropias such as
myopia, hyperopia and regular and irregular astigmatism, and the
retardation of cataract development.
[0004] 2. Description of Related Art
[0005] Vision impairment is an exceedingly common problem in
humans. Nearly 100% of people over age 50 have some form of vision
impairment. The need for corrected vision (e.g., the need for
glasses or contacts) is also very common among younger people. In a
vast majority of people needing vision correction the problem is
associated with the crystalline lens of the eye. Two primary
problems that occur in the crystalline lens are (a) insufficient
flexibility resulting in the inability to correctly focus incoming
light and (b) light scattering also resulting in blurred
vision.
[0006] The common errors of focusing of the eye fall into a class
of visual impairments termed ametropias, which include myopia,
hyperopia, astigmatism (regular and irregular) and presbyopia.
These impairments generally cause visual blurring, and are most
commonly corrected with eyeglasses or contact lenses, and sometimes
with surgery. Myopia is the ocular condition where light from a
distant object focuses in front of the retina resulting in blurred
distance vision, while visual images of near objects are generally
clear. Myopia is the most common reason for vision correction in a
population under age 30. In hyperopia, an image of a distant object
is focused behind the retina, making distance and near vision
blurred, except where described later. Hyperopia, although
exceedingly common, is not normally corrected until the fortieth
decade when presbyopia makes correction necessary. Astigmatism is a
refractive error that results in the eye's inability to focus along
a first axis in a plane perpendicular to the line of sight being
different from the eye's ability to focus along a second axis in
the same plane perpendicular to the first axis, thus producing an
image incapable of focusing at any distance. Astigmatism generally
occurs as a second impairment along with either myopia or
hyperopia, but is occasionally the only reason for needing visual
correction. Astigmatism is subdivided by type and includes regular
and irregular astigmatism as well as aberration. In irregular
astigmatism there are other distortions or aberrations which are in
some persons corrected by considering its effect upon the wavefront
function. The wavefront function characterizes the refractive
profile of the eye and defines irregular astigmatism, which is
considered a higher order optical aberration such as spherical
aberration, coma, trifoil, and others often characterized by
Zernicke polynomials above the fourth order. (See, for example,
Rae, Krueger & Applegate, Customized Corneal Ablation (2001),
which is specifically incorporated herein by reference).
[0007] Of the ametropias, presbyopia stands out as a significant
problem because of its prevalence and because it is not corrected
as successfully as are myopia and hyperopia with the current
treatment methods. Presbyopia is the focusing error caused by a
loss of flexibility of the ocular lens. Lens flexibility allows for
accommodation, which is the primary mechanism by which the eye
changes focus. Accommodation is the change in shape of the ocular
lens as it responds to neural feedback, ideally to focus light
precisely on the back of the retina, allowing the perceived image
to be seen in sharp focus. Presbyopia generally causes clinically
significant blurred vision in humans starting between the ages of
40 and 50 years, and is one of the few human disorders with a
prevalence of 100% in the population that reaches the age of the
mid-50's.
[0008] Functionally, loss of accommodation is a life long process
through which the ability of the ocular lens to change shape to
allow for focused vision continually decreases starting essentially
at birth. This change is evidenced in the following typical data
comparing the eye's focusing ability, here measured by the eye's
shortest focal length in units of diopters (the reciprocal of focal
length measured in meters) to the age of an eye: 14 D. (focal
length at 7 cm) at 10 years; 8.00 D. (f=12.5 cm) at 30 years, 4.00
D. (f=25 cm) at 45 years, and 1.00 D. (f=100 cm) at 52 years.
[0009] Until absolute presbyopia (i.e., no accommodation) occurs,
focusing on close objects is achieved through the control of the
ciliary muscle. Two theories of how this occurs have coexisted for
more than 100 years, and have only recently been clarified by
direct observation with sophisticated cameras and ultrasound
systems. The Helmholz theory first proposed in 1909 basically
defines the crystalline lens as being held in resting tension by
the ciliary muscle when the lens is focused for a distance object.
When the lens focuses on nearer objects, it is through the
relaxation of the ciliary muscle, and releasing of any tension on
the lens, yielding a thicker or more convex lens.
[0010] In addition to presbyopia, it is well known that another
process occurs within the ocular lens throughout a normal human
life that also generally becomes clinically diagnosable during the
fourth decade of life. This second degenerative process manifests
as the scattering of light as it passes through the lens. The
process that leads to light scattering is the first step to
cataract development.
[0011] Cataracts are areas of opacification of the ocular lens of
sufficient size to interfere with vision. They have been
extensively studied because of their high prevalence in a geriatric
population. Cataracts in the aged (senile cataracts) are the most
common type, and are often thought to be due to an acceleration of
the previously mentioned light scatter. Cataracts occur to varying
extents in all humans over the age of 50 years, but generally do
not cause significant visual dysfunction until the ages of 60-80
years. Cataracts, however, can occur much earlier as a result of
risk factors including disease, trauma, and family history.
[0012] FIG. 2 is presented as an aid to understanding the visual
impairments related to the ocular lens (3). The ocular lens (3) is
a multi-structural system as illustrated in FIG. 2. The macroscopic
lens structure includes a cortex (13) just inside a capsule (14),
which is an outer membrane that envelopes the other interior
structures of the lens. The nuclei are formed from successive
additions of the cortex (13) to the nuclear regions, which are
subdivided into a deep fetal nucleus (22), which develops in the
womb, an infantile nucleus (24), a juvenile nucleus (26), and the
adult nucleus (28). On the microscopic level the structure of the
nuclei is layered, resembling the structure of an onion with the
oldest layers and oldest cells towards the center. Rather than
being spherical, the lens is a biconvex shape as shown in FIG. 2.
The cortex and the different nuclei have specific structures that
are consistent through different ages for specific cell sizes,
compactions, and clarity. The lens epithelium (23) forms at the
lens equatorial region (21) generating ribbon-like cells or fibrils
that grow anteriorly and posteriorly around the ocular lens. The
unique formation of the crystalline lens is the biconvex shape
where the ends of the cells align to form a suture in the central
and paracentral areas both anteriorly and posteriorly. Transparency
is maintained by the regular architecture of the fibrils. As long
as the regular architecture is maintained, light passes
unobstructed through the lens. The older tissue in both the cortex
and nucleus has reduced cellular function, having lost their cell
nuclei and other organelles several months after cell formation.
The aqueous (17), the liquid in the anterior chamber between the
lens and cornea flows very slowly through the lens capsule (14) and
the sutures into more remote areas of the lens and provides the
nutrients needed for minimal cellular life functions, including the
removal of toxic and oxidative byproducts.
[0013] The microstructure of the fibrils contains interconnections
between the ribbon-like fibrils called balls and sockets and
interdigitations and imprints, which to some extent inhibit the
relative motion of fibrils with respect to one another. Still, the
fibrils are relatively free to move in relation to each other in
the young, flexible crystalline lens. As the eye ages, there are
age related changes to these structures that include the
development of intermolecular bonding, mostly disulfide bonding,
the compaction of tissue, the breakdown of some of the original
attachments, and the yellowing or darkening of older lens
areas.
[0014] Changes in the size and shape of the macroscopic lens
components throughout life include both the increased curvature and
general enlargement of the biconvex lens with age. The thickness of
the posterior portion increases more than the anterior portion.
Additionally, thickness increases are proportionately greater in
the periphery.
[0015] The above mentioned disulfide bonding immobilizes the oldest
and deepest lens tissue, characteristically seen in the nuclear
regions. However, disulfide bonds are weak chemical bonds, and are
subject to modification and breakage with relatively little energy.
The disulfide bonds are largely formed by the effects of ambient
ultraviolet (UV) light from the atmosphere and from the continual,
unrelenting reduction in lens movement with age (presbyopia). The
lens absorbs fluids from the aqueous, a process enhanced by lens
accommodation, e.g., the undulating movement of the younger
crystalline lens. The aqueous normally contains antioxidants that
aid in preventing disulfide bond formation that further inhibits
lens movement.
[0016] Just as for the mechanism of presbyopia, light scattering
and cataractogenesis results from interfibril attachment. On the
cellular level, all cataracts begin with oxidative changes of the
crystalline tissue. The changes in the lens tissue that lead to
light scattering occur when individual fibers combine to form
large, light-disrupting macromolecular complexes.
[0017] The two different processes that lead to presbyopia and
light scattering occur simultaneously and continuously but at
different rates. The possible connection between the two processes
was clarified by a 1994 report by Koretz et al. (Invest. Ophthal.
Vis. Science (1994)), the entirety of which is specifically
incorporated herein by reference to the extent not inconsistent
with the disclosures of this patent. Koretz et al. studied
extensively the presence of zones of light scatter. They not only
confirmed that older lenses had more light scatter, but also they
reported an acceleration in the rate of formation of
light-scattering macromolecular complexes starting in the fourth
decade of life. Since certain natural antioxidants within the lens
are known to counteract the changes that produce light scatter,
Koretz theorized that reduced lens movement due to decreased
accommodation reduces the flow of fluids carrying the antioxidants
and thereby exacerbates the process leading to light
scattering.
[0018] As further foundation for this discussion, the anatomical
structures of the eye are shown in FIG. 1, a cross sectional view
of the eye. The sclera (31) is the white tissue that surrounds the
lens except at the cornea. The cornea (1) is the transparent tissue
that comprises the exterior surface of the eye through which light
first enters the eye. The iris (2) is a colored, contractible
membrane that controls the amount of light entering the eye by
changing the size of the circular aperture at its center (the
pupil). The ocular or crystalline lens (3), a more detailed picture
of which is shown in FIG. 2, is located just posterior to the iris.
Generally the ocular lens changes shape through the action of the
ciliary muscle (8) to allow for focusing of a visual image. A
neural feedback mechanism from the brain allows the ciliary muscle
(8), acting through the attachment of the zonules (11), to change
the shape of the ocular lens. Generally, sight occurs when light
enters the eye through the cornea (1) and pupil, then proceeds past
the ocular lens (3) through the vitreous (10) along the visual axis
(4), strikes the retina (5) at the back of the eye, forming an
image at the macula (6) that is transferred by the optic nerve (7)
to the brain. The space between the cornea and the retina is filled
with a liquid called the aqueous in the anterior chamber (9) and
the vitreous (10), a gel-like, clear substance posterior to the
lens.
[0019] The traditional solution for the correction of presbyopia
and other refractive errors is to provide distance glasses, reading
glasses, or a combination of the two called bifocals. Other forms
of correction include the following: a) variable focus bifocal or
progressive spectacles, b) contact lenses, c) aspheric corneal
refractive surgery, and d) intraocular implant lenses for aphakic
(absence of the ocular lens) individuals. Bifocal contact lenses
are uncommonly used because, for fitting or for technical reasons,
they are optically inferior to bifocal spectacles. An additional
corrective method using contact lenses called "monovision" corrects
one eye for near and the other for far, and the wearer learns to
alternate using each eye with both open. Aspheric photorefractive
keratectomy (such as is described in Ruiz, U.S. Pat. No. 5,533,997
and King, U.S. Pat. No. 5,395,356, the entire disclosures of which
are specifically incorporated herein by reference to the extent not
inconsistent with the disclosures of this patent) provides variable
focus capabilities through an aspheric reshaping of the cornea.
Similar to this optical correction, some aspherical intraocular
implant lenses take the place of the natural ocular lens in
individuals whose lens has been removed during cataract surgery.
All of these techniques have one or more of the following
disadvantages: a) they do not have the continuous range of focusing
that natural accommodation provides; b) they are external devices
placed on the face or eye; or c) they cut down the amount of light
that normally focuses in the eye for any one particular distance, a
particular problem because middle-aged individuals actually need
more light because of light loss due to the development of light
scattering, as described above.
[0020] Further treatments founded on using nutritional supplements
have been considered to enhance accommodation and retard cataract
development. Additionally, behavioral optometrists proposed many
years ago the use of focusing exercises to slow down the
deterioration of lens accommodation. None of these treatments has
been widely accepted.
[0021] Alternative treatment methods to glasses have been more
successful in correcting such refractive errors as myopia
(nearsightedness), hyperopia (farsightedness), and astigmatism
compared with their limited success in treating presbyopia. Such
alternative treatments use photorefractive procedures in an attempt
to correct refractive errors and avoid the necessity of external
lenses (e.g., spectacles and contact lenses), including the
currently FDA-approved procedures of photorefractive keratectomy
(PRK) and laser-assisted keratomileusis (LASIK). PRK and LASIK
treatments use a laser to produce a unique shape in the static
cornea of the eye that is calculated to precisely focus light at
the retina taking into account the dimensions and limitations of
other structures of the eye, especially the crystalline lens. These
procedures are of limited utility specifically because they treat
the static cornea and do not account for the dynamics of the
crystalline lens, which change over time as evidenced by the
occurrence of presbyopia.
[0022] Another disadvantage of the present photorefractive
procedures is that they generally involve fairly invasive surgery.
For instance, LASIK requires an incision in the cornea to create a
flap of tissue that is peeled back to expose the interior of the
cornea, which is then precisely sculpted to focus light on the
retina.
[0023] For presbyopic correction specifically, current methods
generally require surgical incision and physical penetration of a
portion of the eye. For instance, Werblin (U.S. Pat. No. 5,222,981)
proposed the surgical removal of the clear, intact crystalline lens
for the purpose of correcting presbyopia and other ametropias, and
substituting a multiple interchangeable components-intraocular
lens. Removal of the lens requires an incision through which it can
be removed.
[0024] Another development in photorefractive treatment of
presbyopia is Bille (U.S. Pat. No. 4,907,586), which primarily
describes a quasi-continuous laser reshaping the eye, namely the
cornea and secondarily the crystalline lens in order to correct
myopia, hyperopia, and astigmatism. Bille, however, also proposed
that presbyopia might be corrected by semi-liquification or
evaporation of lens tissue through treatment with a
quasi-continuous laser.
[0025] In WO95/04509 and again later in U.S. Pat. No. 6,322,556,
Gwon described a method to correct presbyopia, myopia, and
hyperopia with an ultrashort laser pulse that produced volumetric
reductions of lens tissue. While various methods to replace the
clear crystalline lens with a flexible or gel intraocular implant
have been developed as an alternate lenticular technology, Gwon's
patented method was the only major milestone in direct treatment of
the natural lens.
[0026] Scleral expansion is a presbyopia treatment method proposed
in patents by Schachar (U.S. Pat. Nos. 5,529,076, 5,503,165,
5,489,299, and 5,465,737). In these patents, Schachar discloses a
method of stretching the sclera, which restores accommodation by
shifting the attachment of the cilliary muscle, allowing the lens
to stretch its diameter. In addition, he suggests an alternative
embodiment involving the use of laser irradiation of the lens to
destroy the germinal epithelium to remove the source of growth of
the crystalline lens. Schachar's method has been described to work
according to the Tscherning mechanism, an alternative mechanism to
the Helmholz theory and is an example of the multiplicity of
presbyopia theories present in the field through the late
1990s.
[0027] Development of crystalline lens modification technology and
presbyopia correction specifically may have been slow after 1990
because the Bille patent was directed (as was other research in the
field) primarily toward the cornea, a simpler system than the
dynamic crystalline lens because it a static refractive
surface.
[0028] Another reason that crystallin lens modification technology
has developed slowly is that ophthalmic professionals are
accustomed to wholly removing the crystalline lens during cataract
surgery, the most commonly performed surgery in the United States
(greater than one million per year). Modifying the crystalline lens
is considered the antithesis of the prevailing thought about lens
removal. Also, ophthalmic professionals have traditionally looked
upon the crystalline lens as susceptible to cataract development
from a wide variety of causes especially trauma such as that of
surgery directly on this tissue. A summary consisting of sixty-nine
pages in Dayson's The Eye (1980), illustrates the wide breadth of
causes of cataracts in the crystalline lens, including ultraviolet,
infrared, and ultrasound energy; incisional surgery from the
anterior (e.g., cornea) or the posterior (e.g., retina); many
systemic diseases including diabetic changes from hyper- to
hypo-glycemic conditions; trauma; toxic chemicals and
pharmacological drugs; and malnutrition and vitamin
deficiencies.
[0029] A reason that laser surgery is of particular interest is
that much of the ocular media is transparent to the visible light
spectrum, i.e., wavelengths of 400-700 nanometers (nm); thus, light
of wavelengths in this range pass through the anterior eye without
effect. While the near-visible spectrum on either side of the
visible range, including ultraviolet and infrared light, has
certain absorptive characteristics in various ocular tissues and
may cause changes in the tissue, the safety of light irradiation
can be specified according to a threshold energy level below which
particular tissues will not be adversely affected. Above the
threshold, ultraviolet or infrared light can cause damage to the
eye, including the establishment of cataracts or even tissue
destruction. The ability to destroy ocular tissue, however, can be
made to be quite beneficial, and is a major premise underlying eye
surgeries using light energy. As described below, light energy can
be focused to a specific point, where the energy level at that
point (expressed as a energy density) is at or above the threshold
for tissue destruction. Energy in the light beam prior to focusing
can be maintained at a energy density below the threshold for
tissue destruction. This "pre-focused" light can be referred to
using the term subthreshold bundles (described by L'Esperance, U.S.
Pat. No. 4,538,608, the entire disclosure of which is specifically
incorporated herein by reference to the extent not inconsistent
with the disclosures of this patent), wherein the "bundles" are not
destructive to tissue.
[0030] Lasers have been used widely to correct many ocular
pathological conditions, including the suppression of hemorrhaging,
the repair of retinal detachments, the correction of abnormal
growth of the lens capsule after cataract surgery (posterior
capsulotomy), and the reduction in intraocular pressure. Therefore,
various laser sources providing numerous and even continuously
variable wavelengths of laser light are well know in the art. The
characteristics of the laser, including its wavelength and
pulsewidth make different types of lasers valuable for specific
purposes. For example, an excimer laser with pulsed UV light of 193
nm has been selected for photorefractive keratectomy (PRK) because
it yields an ablation with very little heat release, and because it
treats the corneal surface without penetrating the cornea. There
are other excimer lasers that use wavelengths from 300-350 nm that
will pass through the cornea and into the lens.
[0031] High energy light having a wavelength in the range from
100-3000 nm can be produced by various types of laser sources,
including those using gases to produce the laser energy, such as
the KrF excimer laser; solid state lasers, such as the Nd-YAG and
Nd-YLF laser; and tunable dye lasers. No matter the laser source,
the physical and chemical effects of coherent light from a laser
upon ocular tissue vary according to a number of laser parameters,
including wavelength, energy, energy density, focal point size, and
frequency. Photodisruption and photoablation describe laser-tissue
interactions in which some tissue is destroyed. The term
photoablation has been used to describe tissue destruction for
photorefractive keratectomy using an excimer laser, as well as for
tissue destruction using infrared lasers. Within this application,
the term photodisruption is used as described below in the Detailed
Description, and may be used herein similarly to uses of the term
photoablation in other references.
[0032] Of the various sources, infrared nanosecond and picosecond
pulsed lasers such as the Nd-YAG and Nd-YLF have been used on the
lens because they can focus for treatment deep in a transparent
system, and because they remove tissue with minimal effect upon
adjacent tissues. The size of the initial tissue destruction using
these lasers is relatively large, however. New generation infrared
lasers performing in the femtosecond range (10.sup.-15 seconds) can
produce a smaller tissue disruption. (See Lin, U.S. Pat. No.
5,520,679).
SUMMARY OF THE INVENTION
[0033] The invention consists of methods for treating the clear,
intact crystalline lens of an eye through the creation of
microspheres, i.e., small, generally spherical pockets of gas
within the lens (i.e., bubbles) for the purpose of correcting
presbyopia, other refractive errors such as but not limited to
myopia, hyperopia, regular and irregular astigmatism, for the
retardation and prevention of cataracts, and treatment of other
ocular anomalies. The creation of microspheres in the crystalline
lens provides for changes in an ocular lens that may include but
are not limited to changes in flexure, mass, and shape. Changes
provided by the creation of microspheres generally improve visual
acuity of the eye in a manner exemplified by but not limited to the
ability to focus more clearly and with a greater range, and to
transmit light without scatter and without distortion. The
invention recognizes that the intact crystalline lens safely can be
treated with a focused, scanning laser, and that treatment of the
crystalline lens for correction of ametropias (including
presbyopia) may be a superior methodology to refractive surgery on
other structures of the eye, including the cornea or sclera, or the
implantation of a flexible intraocular (crystalline) lens implant
or gel. To enhance safety, the present invention may include
concomitant use of antioxidative therapy to minimize any possible
side-effects of acute laser radiation exposure during
treatment.
[0034] In a preferred embodiment, the creation of microspheres
occurs through a mechanism that may be referred to as
photodisruption. The photodisruption mechanism used to create
microspheres, which is described in detail in the following
section, produces the beneficial visual effects mentioned above
(correction of presbyopia and other refractive errors, retardation
and prevention of cataracts, and treatment of other ocular
anomalies) via two primary modes of action that are termed (1)
photophacomodulation and (2) photophacoreduction.
Photophacomodulation refers to any mechanism of light-induced
change in crystalline lens tissue that affects its chemical and
physical properties and thereby alters the dynamic properties of
the crystalline lens including its ability to change shape.
Photophacoreduction refers to any mechanism of light-induced change
in the crystalline lens whereby the change primarily effects a
reduction in the mass or volume of crystalline lens tissue. While
these two terms are intended to be used consistently throughout
this patent, they may be referred to elsewhere respectively using
the terms crystalline lens modulation and volumetric reduction, or
in combination using the umbrella term photorefractive lensectomy.
By either mode of action, the beneficial effects of the invention
are principally achieved through generation of microspheres (as
noted above).
[0035] Embodiments of the invention that utilize the
photophacomodulation mode (effecting a change in the dynamic
properties of the crystalline lens) generally generate individual
microspheres essentially independent from one another, or may
generate individual microspheres that interact, for example by
coalescence after generation. Generally, the methods of the
invention use the photophacomodulation mode to change lens tissue
within the older areas of the ocular lens such as the nucleus, and
particularly within specific regions of the juvenile and adult
nucleus, since older, more compact tissues are thought to be most
responsible for loss in accommodation. In this respect, the present
invention can be contrasted with disclosures of the Schachar
patents previously cited, in which Schachar proposes treatment of
the epithelium, an outer cortex layer, to impair the growth of the
epithelium.
[0036] Embodiments of the invention that utilize the
photophacoreduction mode (effecting volume reduction in the
crystalline lens) generally generate microspheres that overlap on
formation because their respective sites of photodisruption are
contiguous as described below. Generally, the methods of the
invention use the photophacoreduction mode to reduce lens tissue
volume within the younger cortical areas of the ocular lens, often
for the purpose of changing the topography of the exterior surface
of the lens. The photophacoreduction mode, however, may be used
within the nuclear regions as well.
[0037] In a preferred embodiment the methods of the invention such
as photophacomodulation or photophacoreduction can be performed as
outpatient ophthalmic procedure without the use of general
anesthesia and without outside exposure of incised tissue with
possible consequent infection.
[0038] A further benefit of the present invention for presbyopic
correction is that it may actually restore natural accommodation
(i.e., the ability of the lens to change its focusing dynamics),
instead of attempting to correct for presbyopia through the use of
aspherical optics on external lenses, implanted lenses, or the
cornea, or requiring the gaze of the eyes to be translated to two
or more locations as when using bifocal, trifocal, or progressive
lenses.
[0039] In another embodiment, treatment according to this invention
makes possible the retardation of cataract development. As
mentioned above, Koretz observed in 1994 that an inverse
relationship exists between lens accommodation and light scatter
development, and that the processes leading to light scatter
accelerate with decreasing accommodation. In view of the corollary
that maintaining or increasing accommodation limits the increase of
or reduces light scatter, by surgically increasing accommodation,
as mentioned above, embodiments of the present invention may reduce
current and anticipated future increases in light scatter. It is
hypothesized that such a reduced rate for the processes leading to
light scatter is achieved, at least in part, through increased
aqueous circulation within the crystalline lens, which results from
increased accommodation. As well, the present invention encompasses
the creation of microchannels through the photodisruption process
that would enhance aqueous circulation within the lens and thereby
lead to reduced light scatter. This cataract retardation effect is
differentiated from cataract removal (partial or full) and cataract
prevention. Cataract retardation has been suggested elsewhere
through the use of pharmaceuticals such as antioxidants used over
long periods of time that allow for maintaining the transparency of
the lens. In this invention, we disclose the use of antioxidants,
but only for treatment of the acute or immediate effects of the
laser therapy during and after lens irradiation. It is the longer
term effects of laser therapy that may lead to a reduction in
cataract development through use of certain embodiments of this
invention. Whereas cataract removal traditionally has meant the
total removal of the lens except for the posterior capsule, and
Gwon (U.S. Pat. No. 6,322,556) has proposed removing partial
cataracts, both complete and partial removal are different from
cataract retardation, which is a benefit of embodiments of this
invention.
[0040] Further objects and advantages of the invention will become
apparent from a consideration of the drawings and ensuing
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0041] FIG. 1 shows the gross anatomy of the eye.
[0042] FIG. 2 is an enlarged view of the crystalline lens showing
its internal structure.
[0043] FIG. 3 shows a general schematic of the instrumentation used
in embodiments of the present invention.
[0044] FIG. 4 depicts the mechanism of microsphere formation by
photodisruption.
[0045] FIG. 5 illustrates examples of the results of treatment by
the individual microsphere formation methodology.
[0046] FIG. 6 depicts a mechanism of individual microsphere
interaction producing a beneficial separation of lens fibrils.
[0047] FIG. 7 depicts microchannels created in a lens.
[0048] FIG. 8 depicts the results of cavity formation or volume
reduction within the lens, resulting in a new lens surface
topography.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0049] FIG. 3 provides a basic illustration of the instrument (400)
used to perform lenticular refractive surgery (LRS). A laser (402)
produces a collimated beam (410) of light having essentially a
single wavelength. The laser (402) preferably generates a beam of
short duration, high frequency pulses such as discussed in Lin
(U.S. Pat. No. 5,520,679), the entire disclosure of which is
specifically incorporated herein by reference to the extent not
inconsistent with the disclosures of this patent, but may be any
laser that provides a beam of sufficient energy and that can be
controlled to perform the treatment herein described. The laser
beam (410) passes through a beam control system (406), likely
comprising mirrors and lenses, for example mirrors (405) and lenses
(407), that direct the light in three spatial dimensions and create
vergence in the beam. The output from the beam control system (406)
is a converging beam (412) that passes through a patient's cornea
(420) and is focused on the surface of or within a patient's ocular
lens (424) for purposes of treating ametropias and retarding
cataractogenesis. The focal point (426) of the converging beam
(412) is capable of traversing any point within the
three-dimensional space occupied by the ocular lens (424). The
surgeon combines knowledge of the patient, the expected ametropias
(including presbyopia) to be altered, and lens biometric
measurements determined by standard ophthalmic instruments to
develop a treatment strategy. Certain of this data is transformed
by a computer algorithm that controls the instrument (400) during
the treatment, including control of laser parameters such as focal
point location, energy level, and pulse duration and frequency.
Focal point location during treatment is determined by a scanning
program that may be used to reduce unwanted, short-term effects on
lens tissue by moving the laser focal point among various areas of
the lens, instead of treating immediately adjacent lens areas. A
detailed description of an instrument similar to the one shown in
FIG. 3, but used for cataract removal, is provided by L'Esperance,
Jr. in U.S. Pat. No. 4,538,608, the entire contents of which are
specifically incorporated herein to the extent not inconsistent
with the disclosures of this patent. Note that in a preferred
embodiment the surgeon would receive real-time feedback regarding
the precise location of the focal point within the ocular lens and
the structural changes as they are occurring. Such data may be
obtained by the surgeon through the use of instruments and methods
now known to one skilled in the art, or which may be later
developed. Advances in eye surgical procedure may easily be
incorporated into a procedure that utilizes an embodiment of the
present invention.
[0050] In an embodiment, the LRS patient is prepared as in cataract
surgery or other laser refractive surgical procedure (e.g., PRK).
The anterior segment of the eye is prepared by procedures that are
common to regular vision testing, including topical anesthetic,
dilating drops, and cycloplegia (temporary paralysis of
accommodation). Biometric measurements of the lens are taken by
A-scan, high frequency ultrasound (B-scan), optical coherency
tomography (OCT), or similar instrumental procedures to determine
the exact dimensions of the lens, including the geometric center,
thickness, and other contour measurements of the nucleus and
cortex. Then the eye is held stationary by patient fixation on a
coaxial light source. Fixation can be further controlled by a
transparent applanation plate fixed to a suction ring on the
anesthetized cornea and coupled to the optical pathway of the
instrument. The surgeon aligns the instrument and the eye using at
least one non-therapeutic helium-neon laser (404), which is focused
by the surgeon in the lens at the focal point (426). Once the
patient is prepared and the instrument aligned, treatment may
begin.
[0051] The basis of LRS treatment is the laser induced
photodisruption process occurring in the crystalline lens and
depicted in FIG. 4. Note that the ocular lens with all of its
internal structure (shown in FIG. 2) forms a single unitary
structure such that reference to locations "in" or "within" the
lens include locations "on" the lens, and the former terms (in and
within) will generally be used throughout this patent to include
the latter (on).
[0052] The photodisruption process is described as follows,
beginning with reference to FIG. 3. The convergent laser beam (412)
enters the eye through the cornea (420) as light waves, which have
been described by L'Esperance (U.S. Pat. No. 4,538,608) as bundles
of energy. The laser beam (412) passes through the cornea (420)
without damage to that tissue because the energy density (referred
to generally as "energy" and also called fluence or fluxure) of the
laser within this tissue is at subthreshold levels. That is, only
above a threshold energy density not obtained by the laser beam
(412) within the cornea (420) will tissue damage occur. See Lin
(U.S. Pat. No. 5,520,679) and L'Esperance (U.S. Pat. No.
4,538,608). During LRS treatment, however, the threshold energy
level (energy density) is attained or surpassed at the focal point
(426) of the converging laser beam (412) within the ocular lens
(424). Given that sufficient energy is incident at the focal point
(426) the process of photodisruption occurs.
[0053] Photodisruption as the term is used herein is a complex,
multistep, sequential process, as illustrated in FIG. 4. When a
laser pulse (502) traveling the path of the converging beam (412)
reaches a first focal point (426) a very small amount of lens
tissue (510) is destroyed in a volume essentially centered on that
first focal point (426). The volume of lens tissue (510) destroyed
depends upon the characteristics of the particular laser pulse
(502) (pulse width, wavelength, energy, etc.) incident on the lens
(424) and the characteristics of the lens tissue itself. For
typical LRS procedures using today's laser technology this volume
is likely in a range from about 0.1-500 .mu.m.sup.3 (e.g., a sphere
having a diameter of 0.5-10 .mu.m). The laser energy incident at
the first focal point (426) breaks molecular bonds and ionizes
molecules and atoms, converting the tissue (510) at the first focal
point (426) from a solid to a plasma (512). At the relatively high
energy level of the plasma (512), the matter that has been
converted occupies significantly more volume than it did as the
solid tissue. Thus, there is a substantial, rapid expansion of the
volume occupied by the converted matter, which generates a "hole"
in the lens (occupied by the plasma (512)) and creates a shock wave
(514) that resonates outwardly from the first focal point (426)
into the surrounding tissue. For typical LRS procedures using
today's laser technology the shock wave may extend from about
10-500 .mu.m from the focal point. Note that the distance the shock
wave travels is highly dependent on the pulse width of the
laser.
[0054] As the procedure continues, the focal point of the laser is
moved to a different location in the lens according to the scanning
program, and the plasma (512) about the first focal point (426)
rapidly converts to a gas (516). The gas (516) fairly rapidly
obtains a state of relative equilibrium as compared with the state
of the high energy plasma (512). The volume occupied by the gas
(516), which is essentially centered on the first focal point
(426), is referred to herein as a microsphere. Just as for the
volume of tissue (510) destroyed at the focal point (426), the
volume of the microsphere (516) depends on all of the laser
parameters as well as the tissue characteristics, but for typical
LRS procedures using today's laser technology the size of the
microsphere will typically be in the range of about 60-15,000
.mu.m.sup.3 (e.g., a sphere of diameter 5-30 .mu.m). The volume of
the microsphere may be less than the maximum volume occupied by the
plasma (512) immediately after expansion due to the altered
lenticular system arriving at a state of relative equilibrium after
the shock (514) of plasma creation, but could be of greater volume
than the plasma (512). The gas in the microsphere, however, is not
likely to be in a true equilibrium and eventually likely will be
absorbed by the lens tissue causing the microsphere to collapse.
Absorption of the gas in the microsphere may occur almost
instantaneously, may take up to several days, or may take a longer
time. It is possible that in some circumstances the microsphere
will not collapse during an extended period of time.
[0055] The creation of a microsphere is common to multiple
embodiments disclosed herein, yet there are several different
methodologies for utilizing the creation of microspheres in
performing lenticular refractive surgery (LRS) as is illustrated in
FIGS. 5-8. The various methodologies of the invention include (1)
individual microsphere formation (FIGS. 5-6), (2) microchannel
formation (FIG. 7), and (3) cavity formation or volume reduction
(FIG. 8). Each of these methodologies, while distinct, has the
potential to both increase the accommodation of the ocular lens and
concurrently, consequently, or alternatively, to increase the fluid
volume that passes through the various layers of the ocular lens in
a given period of time. Such changes likely are the mechanisms
whereby embodiments of the present invention effect treatment of
ametropias, including presbyopia, and prevention or retardation of
light scattering and cataractogenesis.
[0056] In an embodiment of the present invention using the
individual microsphere formation methodology, the results of which
are illustrated in FIGS. 5A-E, numerous individual microspheres
(520) are created within the ocular lens (522) in a pattern of
predetermined form. The numbers of individual microspheres that are
applied to the crystalline lens may vary from a few to hundreds of
thousands or more. In the experiments described in the Examples
below the number of microspheres applied to a lens has exceeded
300,000. It is generally believed that the application of greater
numbers of microspheres is more beneficial. Particularly as
technology advances and the microspheres can be made smaller the
number of microspheres applied to a lens during a single treatment
regimen can be expected to increase further. An anticipated limit
to the number of microspheres applied may be provided by the ratio
of a minimum microsphere volume that is effective for producing
visual improvement in a patient and the volume of the lens being
treated.
[0057] As an example of this individual microsphere methodology,
FIG. 5A depicts a lens (522) treated with microspheres (520) having
an aggregate pattern that is an annulus. When using this
methodology, individual microspheres (520) may be created at
positions within the lens that are separated by sufficient distance
so that the microspheres remain predominantly separate, i.e., as a
result of the lens tissue characteristics the majority of
individual microspheres do not coalesce with an adjacent
microsphere. The distance between microspheres necessary to
maintain their individual nature will vary, depending on lens and
laser characteristics, from about 1 .mu.m to about 1 mm, but when
using today's technology in the preferred embodiment it will
generally be in the range of 10-15 .mu.m. Additionally, when the
placement of microspheres occurs in locations such that a
microsphere is anterior to a more posterior microsphere, the more
posterior microsphere will be applied first in order to keep the
more anterior microsphere from interfering with the creation of the
more posterior microsphere.
[0058] The useful patterns of microsphere creation in the lens are
essentially limited only by the skill of the surgeon operating the
instrument. Shown in FIGS. 5A-E are various examples of microsphere
patterns in an ocular lens (522). FIGS. 5A-D show a cross section
of a crystalline lens laterally oriented as though viewed through a
dilated eye and pupil (coronally). FIG. 5 E is a cross section of
the lens oriented sagittally (ninety degrees rotated from FIGS.
5A-D). FIG. 5A shows an annulus; FIG. 5B shows a disk; FIG. 5C
shows radially aligned wedges; FIG. 5D shows radial lines; and FIG.
5E shows the annulus of FIG. 5A or the radial lines of FIG. 5D from
a sagittal view. The patterns of microspheres (520) may be applied
to the lens essentially throughout the lens volume, except that
treatment by LRS generally is intended not to violate the lens
capsule (14), which maintains the physiological integrity of the
lens and the surrounding aqueous (17) and vitreous (10).
[0059] There may be some hesitancy among practitioners to treat the
center of the ocular lens along the visual axis, such as by
utilizing the disk pattern shown in FIG. 5B. Such hesitancy may
arise because of a perceived risk to disrupting lens tissue in the
central region of vision (i.e., along the visual axis). Yet,
because the microspheres generally collapse in due time, leaving in
their absence a volume of lens tissue in the immediate vicinity of
the once present microsphere that transmits light without visual
disruption, there may be no clinical reason not to apply
microspheres within the visual axis.
[0060] In an alternate embodiment individual microspheres are
created at such distances from one another that at least some
microspheres do coalesce. An illustration of how an individual
microsphere may act in concert with another microsphere through
coalescence is provided in FIGS. 6A-D. In FIG. 6 the fibrils (612)
of the lens are depicted as straight lines equidistant from one
another. Note that the elements of FIG. 6 are not drawn to scale,
but are depicted in a manner that enhances the illustration of this
written description. As described above, the converging laser beam
(412) is focused at the focal point (426) within the lens, and by
the process of photodisruption a first microsphere (516) is
created, pushing apart or cleaving the fibrils (612) in the
vicinity of the first microsphere (516). The energy of creation of
the first microsphere is in the first instant contained within the
fibrils adjacent to the first focal point and the interstices
therebetween as shown if FIG. 6B. However, the forces resulting
from microsphere creation, including plasma formation and the
consequent shock wave (514) will likely cleave the laminar fibrils
of the crystalline lens along the boundary between the fibrils. The
cleavage of laminar fibrils of the crystalline lens by a dull
surgical tool has been described by Eisner in Eye Surgery (1980),
which is explicitly incorporated herein by reference to the extent
not inconsistent with the disclosures of this patent. As LRS
treatment continues, a second microsphere (517) is created,
cleaving fibrils in its vicinity. The forces of microsphere
creation that cleave fibrils (612) are such as to extend the
separation between the fibrils (612) along the distance between the
microspheres (516 and 517). The separation may extend along the
entire distance between the microspheres (516 and 517) as shown in
FIG. 6D. At the point that the separation between fibrils (612) has
extended along the entire distance between microspheres (516 and
517), the microspheres will merge into a single expanded
microsphere (515), as shown in FIG. 6D.
[0061] Also shown in FIG. 6 is a representation of the
interconnections (518 and 519) between fibrils (612). These
interconnections could be any form of engagement between fibrils,
including interdigitations, van der Waals attractions, or disulfide
bonds. The separation of fibrils (612) may be such that the
interconnections (518 and 519) are disrupted to the extent that
they no longer act to connect the fibrils (612), as shown in FIG.
6D. Both the separation of fibrils and the disruption or
disengagement of the interconnections (518 and 519) allows a
greater range of motion of fibrils (612) with respect to one
another, including a greater ability to translate relative to one
another. This greater range of motion, in turn, leads to increased
flexibility of the crystalline lens as a whole, or at least in the
region treated, which results in greater accommodation and,
therefore, correction of presbyopia. Thus, the present invention is
theorized to effect increased accommodation by decreasing tissue
density and disrupting fibril interconnections.
[0062] While it is shown in FIG. 6 that disengagement of the fibril
interconnections occurs as a result of the interaction or
coalescence of microspheres (FIG. 6D), the same disruption or
disengagement can and does occur via application of a single
microsphere. As described above the creation of a microsphere will
likely cleave the laminar fibrils along the fibril boundary.
Because cleavage along fibril boundaries may occur whether or not
microspheres coalesce, similar beneficial results (e.g., increased
accommodation) may be achieved in either instance.
[0063] When using the individual microsphere formation methodology,
microspheres are generally applied to areas of the crystalline lens
which are the least flexible. In particular the juvenile nucleus
(26) and the adult nucleus (28), seen in FIG. 2, are denser tissues
within the lens and are considered the least flexible, and
therefore are likely areas of treatment. In addition, it may be
advantageous to treat other areas of the nucleus, including the
infantile nucleus (24) where the older tissue is not so compacted,
and even the cortex (13). Treatment of these older, denser, and
less flexible areas is likely to have greater benefit than
treatment elsewhere in the lens since the fibril structure of the
older, denser lens areas is known to contain greater chemical
cross-linking, more interfibril engagements, more compaction, and
less transparency. Therefore, treatment of these less flexible
areas with individual microspheres as described above may well
achieve a decoupling of fibrils, i.e., a tearing apart of the
macromolecular structures that form in the older lens tissue by
breaking cross-linkages, disengaging interfibril engagements and
generally separating the compacted layers of the lens tissue (e.g.,
as shown in FIGS. 6A-D).
[0064] The presentation of microspheres to the lens, i.e., the
creation of microspheres in the lens as just described, is a
technique that induces a softening of lens tissue. In particular,
the creation of microspheres in the ocular lens and the consequent
disruption of fibril interconnections (518 and 519) can lead to a
greater flexibility and an increased range of motion of the fibrils
(612), which, in turn, may generate an increase in lens
accommodation or allow for the maintenance of the present level of
accommodation for a longer period of time, and therein may be a
treatment for visual impairments, especially for presbyopia. Using
the methodology of individual microsphere formation to treat a
presbyopic lens may generate increased accommodation in the range
from 0-8 Diopters, which can have the effect of providing a 45
year-old lens with the flexibility of a typical 35 year-old lens.
As described above, when discussing Koretz's observations, such an
increase in or maintenance of accommodation may also aid in
reducing light scatter or reducing the rate at which light scatter
is created.
[0065] In alternate embodiments of the individual microsphere
formation methodology, in addition to or as an alternative to the
benefits in relation to reducing presbyopia, increasing
accommodative potential may correct some amount of myopia,
hyperopia, astigmatism, or aberration. That is, an increase in
accommodation may provide the lens the added flexure and
biomechanical changes needed to correctly focus an image in
response to neural feedback, thereby correcting myopia, hyperopia,
astigmatism, or aberration.
[0066] In a further embodiment using the individual microsphere
formation methodology, it is also possible to achieve targeted
flexural changes in the ocular lens, that is, flexural changes at
specific locations or within certain regions, so as to generate
useful biomechanical differentials across the lens volume. These
biomechanical differentials may include differential flexibility or
thickness between regions. Purposely creating a lens wherein
certain regions are more flexible or thicker than others may allow
for improved focusing capability. For example, for the correction
of hyperopia, achieving more flexure along the visual axis (4), as
opposed to the periphery of the lens, would allow a greater range
in lens shape through the center of the lens so that when tension
on the crystalline lens was relaxed, the lens would be more convex
than before treatment, correcting the hyperopia to at least some
extent. Similarly, myopia might be corrected by the application of
individual microspheres to achieve targeted biomechanical changes
in the ocular lens at the periphery, the visual axis, or at some
other location, so as to allow for a less convex lens shape when
the crystalline lens is under full constriction as it would be when
viewing a distant object. The creation of biomechanical
differentials in flexibility and thickness are particularly
important with respect to the treatment of astigmatism because the
focusing potential of the lens must be the same in the all focal
planes.
[0067] In another embodiment of the present invention, the results
of which are illustrated in FIG. 7, microspheres are created within
the ocular lens (3) in close proximity to one another in a
generally sequential pattern from posterior to anterior positions
in the lens. In this embodiment the microspheres are created at
positions within the lens that are separated by an insufficient
distance to maintain the individuality of the microspheres. Not
only are the individual microspheres created close enough to one
another that they do coalesce, but also according to this
embodiment the small volumes of tissue removed (e.g., volume 510 in
FIG. 4) are contiguous. By moving the laser focal point generally
in an anterior direction from the starting point (534), and
removing contiguous volumes of tissue (e.g., volume 510 in FIG. 4),
an open channel (530) in the lens tissue can be created. This open
channel (530) is referred to as a microchannel (530) and is
different from the embodiment described above and illustrated in
FIG. 6 in which the microspheres are placed close enough to
coalesce but in which the small volumes of tissue removed are not
contiguous. An additional difference from the embodiment
illustrated in FIG. 6 is that a microchannel of this embodiment
traverses a path generally perpendicular to the length of the
fibers. Even though some of the gas created in the microchannel
during the photodisruption process may be absorbed by the remaining
lens tissue, sufficient lens tissue mass has been removed along the
path of the microchannel that even with some reduction in channel
volume due to gas absorption, the channel remains generally open.
Also different from the embodiment of FIG. 6, the microchannels of
this embodiment are created in such dimension--i.e., sufficient
tissue volume is removed--that they remain as open channels long
after the surgery, possibly on the order of years or longer.
[0068] The microchannel (530) is generally characterized by a path
length from the starting point (534) to the endpoint (532) that is
greater in distance than any channel dimension perpendicular
thereto. That is, if the microchannel is created having a generally
circular cross section, its length is greater than the cross
section diameter. The starting and ending points (534 and 532) for
the microchannels may be the sutures which are known to be a part
of the fluid flow system of the lens. While the length of a
microchannel is generally along a path essentially parallel to the
visual axis, the microchannel may follow a non-linear path along a
length in the general direction from posterior to anterior. As
well, although the circular cross section is the preferred shape,
any feasible cross sectional shape may be used.
[0069] The microchannels aid in fluid transport through the
structures of the ocular lens, thereby allowing an exchange of
antioxidants, nutrients, and metabolic by-products between the
aqueous and portions of the lens to which there was previously
insufficient fluid flow. As described in the Background section the
older tissues in the lens, primarily in the nucleus (12), are
generally more dense and show a build-up of cellular by-products.
The increased fluid transport in these older tissues such as is
allowed by the microchannels may retard or reverse the processes
that lead to declining accommodation (i.e., presbyopia) and light
scattering. The microchannels may be used alone as a treatment
strategy or may be used to supplement the enhanced fluid flow
generated by increasing the flexure of the lens for the correction
of presbyopia.
[0070] In another embodiment, illustrated in FIG. 8, mass and
volume reduction of the lens tissue generally at the periphery is
accomplished through the creation of microspheres in such proximity
that the small volumes of tissue removed (e.g., volume 510 in FIG.
4) in the photodisruption process are contiguous. This methodology
is generally referred to as photophacoreduction. While the
methodology is essentially the same as in the previous embodiment
in which microchannels are created through tissue removal, the
location, geometry, and purpose of the volume removal of this
embodiment is substantially different.
[0071] In this embodiment the removal of contiguous volumes by
photodisruption creates a cavity (15) in the cortex (13) as opposed
to the nucleus (12) of the ocular lens (3). FIG. 8A shows the
location of the cavity (15) in the lens (3) where the lens (3) is
still in the shape it had prior to cavity (15) formation. The
cavities (15) can follow the contour of a fibril layer of the lens
to reduce the numbers of fibers that are interrupted, or may be
created to maximize the number of fibers interrupted. The result of
the procedure of this embodiment is a collapse of the capsule (14)
in the region of the tissue removal wherein the path of the capsule
(16) prior to the collapse is longer and located generally anterior
to the path of the capsule (18) after collapse. FIG. 8B shows the
lens shape after collapse of the cavity (15), at which time, as a
result of the collapse, the cavity (15) is no longer present in the
lens as remaining lens tissue has collapsed into the cavity (15).
Due to cavity (15) formation the lenticular capsule (14) may also
loosen causing a reduction in the useful energy imparted to the
lens by the zonules. If necessary the capsule can be tightened by
thermoplasty using infrared radiation without opening a hole in the
capsule. Using thermoplasty reduces the length of the lens capsule
(14) in the region about the volume reduction. Collapse of the lens
(3) may occur naturally as a result of volume removal, or may be
induced as a result of capsule thermoplasty. Treatment by
photophacoreduction may best be accomplished in the less dense
tissues of the cortex (13) or the infantile nucleus (24), but
otherwise may be performed in essentially any lens location.
[0072] Generally, in the embodiment shown in FIG. 8, the procedure
will be performed for the purpose of altering the exterior
topography of the ocular lens as a method for correcting ametropias
other than presbyopia. The beneficial effect of this embodiment may
be a change in the refractive power of the lens at the location at
which a topography change occurs so as to lessen or remove
completely the myopic, hyperopic or astigmatic condition of a
person's vision. Cavities toward the optical center cause a surface
collapse that produce a less convex anterior or posterior surface,
and that reduce myopia. Alternatively, placing the cavity toward
the equator may reduce hyperopia. Creating a cavity of varying
thickness induces lenticular astigmatism which may counteract an
existing astigmatism. While a change in refractive power is a
possible benefit, the lens capsule collapse may also cause a
different angular insertion to the zonules and may thereby provide
a more efficient ciliary muscle action allowing for some correction
of myopia, hyperopia, and presbyopia. An additional benefit to the
removal of lens mass and volume near the periphery, however, may be
an increase in accommodation.
[0073] A further alternative embodiment is the prevention of
cataract formation through any of the methodologies described
above: 1) individual microsphere formation, 2) microchannel
formation, and 3) volume removal. While there is a connection
between presbyopia and the development of light scatter and lens
opacification, success in cataract retardation may be independent
of the success of treatment for presbyopia.
[0074] In an alternative embodiment, the application of numerous
individual microspheres may produce a combined net increase upon
the lens thickness that will also result in an increase in
accommodation. The additional volume that results from microsphere
formation may vary as the lens is pulled upon by the ciliary muscle
and alternately relaxed. Due to the effects of tension on the lens,
the additional volume from microsphere formation may be greatest
when the lens is relaxed. The result of this kind of relaxed volume
change depending on the tension in the lens is actually an increase
in accommodation.
[0075] A still further alternate embodiment is the concomitant use
of drugs to reduce inflammation and the effects of free radicals
and debris within the lens portions of the eye before, during, and
after the procedure. Antioxidative drugs, such as galactose,
glutathione, and penicillamine, can react locally with any active
by-products and facilitate the reduction of free radicals generated
during the surgery. These drugs enter the circulatory, lympathic,
and intraocular systems after oral or topical administration, then
naturally penetrate the lens matrix from the aqueous. After
treatment according to an embodiment of this invention, their
transport may be aided by the newly gained flexure as well as newly
created microchannels. Also, anesthetics, mydriatics and
cycloplegics are used at the time of the treatment as in other
intraocular surgeries. Miotics for pressure control,
corticosteroids and/or non-steroidal anti-inflammatory drugs
(NSAIDS) also may be used after surgery.
[0076] Each of the methodologies just described can be carried out
using lasers for which the emitted light has a variety of physical
parameters. The light used may be in wavelengths from ultraviolet
through visible and into the infrared regions of the
electromagnetic spectrum, any of which wavelengths may be useful in
carrying out embodiments of this invention. A range of wavelengths
from about 100 nm to about 2000 nm may be useful in embodiments of
this invention. Because of the general transparency of the tissues
of the anterior portions of the eye to visible light (allowing
visible light to pass through the eye and to be focused on the
retina), the preferred wavelength ranges do not include the visible
wavelengths but are in the ultraviolet region from about 310-350 nm
and in the infrared region from about 700-1500 nm. There are
advantages and disadvantages to each of these ranges as mentioned
previously. The most preferred wavelengths, and those which have
been most extensively tested for use in embodiments of this
invention are the infrared wavelengths from about 800-1300 nm, and
particularly from about 800-1000 nm.
[0077] Preferred ranges for other laser parameters include the
following. The preferred pulse width is in the range from about 1
fs to about 500 ps, with the more preferred range being from about
50 fs to about 500 fs. The preferred pulse energy has the range of
about 0.1 mJ to about 10 mJ per pulse with the more preferred range
being from about 0.5 to about 50 mJ per pulse. The preferred
frequency for pulse delivery has the range of about 1 Hz to about
50,000 Hz, with a more preferred range of about 1,000 Hz to about
20,000 Hz. The pulse energy would be within the range of about 0.25
mJ/pulse to about 1 J/pulse, the more preferred range being from
about 0.5 mJ/pulse to about 50 mJ/pulse.
[0078] Steps included in embodiments of the present invention to
maximize the safety and efficacy to the lens and other vital parts
of the eye during treatment include maintaining the lens capsule
intact, i.e., keep from physically destroying the lens capsule,
which would otherwise thereby allow the lens contents to have an
opening to the aqueous, which is well known to cause cataract.
Another safety procedure is to control the cone angle of the laser
beam such that extraneous light not absorbed by interactions at the
focal point is masked by inert posterior matter from damaging other
tissue. Preferred cone angles range from about 2 degrees to about
40 degrees, with the more preferred cone angles being from about 5
degrees to about 15 degrees. Further, control of light energy
parameters (e.g., wavelength, pulse frequency, etc.) and the use of
pharmacological agents may be used to minimize pathological changes
to the cornea, equatorial (germinal) lens epithelium and fibril,
ciliary body, and the perimacular region of the retina.
[0079] While a fairly specific mechanism has been described for the
process of photodisruption, other mechanisms are encompassed by
this invention. Any mechanism through which a microsphere as
described herein can be created may work to produce the beneficial
results described herein. The various mechanisms by which a
microsphere may be created in the crystalline lens include those
that result from the application of a wide variety of energy
sources. Discussed in detail herein is the use of laser light
(particularly in the infrared and ultraviolet wavelengths) as an
energy source for creation of a microsphere, but any energy source
and delivery method that can be used to create a microsphere in the
crystalline lens may be suitable for use in this invention.
Alternate sources of energy include but are not limited to
mechanical sources such as a water jet or scalpel, sound or
ultrasound energy, and heat.
[0080] In an alternate embodiment, any of the above described
methodologies can be performed with the use of a probe inserted
through a corneal incision for the purpose of delivering the energy
necessary to create the microspheres. Use of a probe to deliver
energy would allow light energy and various other methods of
transferring mechanical energy, such as by water jet, to be
utilized in embodiments of this invention. In this alternate
embodiment the probe for delivery of energy may abut the lenticular
surface or may be held at some distance therefrom. This alternative
embodiment is preferred for the delivery of sources of energy that
are not efficiently transported through the anterior portions of
the eye.
[0081] Presently, the preferred group of patients on which to carry
out this treatment is emmotropic low hyperopic subjects with
spectacle prescriptions of less than 3.00 D. Preferred patients are
pre-presbyopic, in their early 40's, with 3-5 Diopters of
accommodation, and have undergone a full-dilated eye exam to
determine the following: a) no prior history of eye disease,
trauma, cataracts, or collagen vascular disease; b) normal
gonioscopic findings; and c) no significant systemic diseases.
[0082] The properties of the crystalline lens and lasers identified
herein allow for treating the clear, intact, crystalline lens for
the purpose of correcting presbyopia, refractive errors, higher
order aberrations, and other disease conditions including cataract
prevention and retardation. A multiplicity of methodologies makes
it possible to address the various probable causes of presbyopia.
The result of treatment for presbyopia according to an embodiment
of this invention is likely to restore from five to eight diopters
of accommodation and to postpone presbyopic development for 5-8
years or more. The same processes of lenticular hardening and
enlargement will continue after treatment and will eventually cause
a reduction in accommodation, resulting in delayed presbyopia onset
after treatment. An additional treatment may prove safe and
efficacious, which would further delay presbyopia. In at least one
embodiment, all of the changes to the crystalline lens are made
under the control of a computerized laser, which can make specific
modifications either separately or together for the treatment of
presbyopia, myopia, hyperopia, and astigmatism, as well as for
cataract prevention and retardation.
Examples
Cadaver Lens Study
[0083] As a first step, a precision technique was verified on 36
human cadaver lenses, where the age-dependent, flexural
characteristics of the lenses were compared with results in studies
of other designs. In the second step, an Nd-YAG laser was used to
produce a 2-4 mm annulus in one of a pair of lenses from 11 donors
while the fellow lens was kept as the control. The Nd-YAG pulse
produced microspheres in the range of 50-500 .mu.m diameter. An
annular laser pulse pattern of 100 suprathreshold pulses were
placed in the center of the treated lens, to produce a doughnut
shaped pattern of microspheres. A simulated accommodation was
created using a rotating base upon which the lens revolved at up to
1000 rpm. Rotational deformation was measured by changes in the
central thickness and in anterior lens curvature as measured by two
different techniques. When comparing the matched lenses, lens
flexibility differences were demonstrated by statistically
significant differences in lens curvature and thickness. That is,
rotational deformation flattened the curvature and decreased the
thickness of the treated lens, compared to the untreated, less
flexible lens. Dioptric changes were calculated at as much as 8
diopters of change. The greater lens formation among laser treated
lenses compared to their fellow untreated control lenses showed
that the first demonstrated example of increasing flexure and
accommodation by laser treatment of the crystalline lens, and
therefore photophakomodulation may be a possible lens treatment for
presbyopia.
[0084] Saftey Study
[0085] Six rabbits were treated in one eye with a femtosecond laser
generating approximately 300,000 microspheres in either of two
patterns, an annulus or radial lines, and at various degrees of
microsphere separation. The study was set up to observe
cataractogenic potential of microspheres in live animals three
months after laser treatment. The animals were sacrificed at three
months and their lenses were examined for early and advanced
cataract formation through gross viewing, light and electron
microscopy. Furthermore, optical quality tests using known scanning
laser light scattering techniques over the full cross section of
the lens demonstrated no increase in light scatter or refractive
distortion in treated lenses relative to their match controls. The
results and implications of this study to the invention were as
follows. [0086] a) Ultrashort low energy pulses can be efficiently
delivered transcorneally into the lens nucleus and cortex of living
subjects. [0087] b) Femtosecond laser pulses of low energy produce
very limited lens tissue disruption with a myriad of small
microspheres. Initially, a ground glass appearance over the treated
area is seen, was not present grossly or under magnification after
three months. [0088] c) No optical distortion was seen using
exacting, diffractional techniques three months after the lens was
treated and compared with its control lens. [0089] d) No
cataractous changes were seen grossly in the lenses, except in one
instance where both the treated and untreated excised lenses
developed cataracts. [0090] e) Electron microscopy showed limited
disruption of lens tissue adjacent to the treated area. There is
small electron dense film at the juncture of the microsphere and
other tissue.
[0091] While the present invention has been disclosed in connection
with certain preferred embodiments, this description should not be
taken as limiting the invention to all of the provided details.
Modifications and variations of the described embodiments may be
made without departing from the scope and spirit of the invention.
Various and multiple alternate embodiments are encompassed in the
present invention disclosure as would be understood by one of
ordinary skill in the art.
* * * * *