1. Field of Invention
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.
2. Description of Related Art
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
As further foundation for this discussion, the anatomical structures of the eye are shown in
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 Davson'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.
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.
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.
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.
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 (10−15 seconds) can produce a smaller tissue disruption. (See Lin, U.S. Pat. No. 5,520,679).
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.
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).
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.
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.
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.
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.
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.
Further objects and advantages of the invention will become apparent from a consideration of the drawings and ensuing description.
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.
The basis of LRS treatment is the laser induced photodisruption process occurring in the crystalline lens and depicted in
The photodisruption process is described as follows, beginning with reference to
Photodisruption as the term is used herein is a complex, multistep, sequential process, as illustrated in
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 μm3 (e.g., a sphere of diameter 5-30 μm). 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.
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
In an embodiment of the present invention using the individual microsphere formation methodology, the results of which are illustrated in
As an example of this individual microsphere methodology,
The useful patterns of microsphere creation in the lens are essentially limited only by the skill of the surgeon operating the instrument. Shown in
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
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
Also shown in
While it is shown in
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
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.
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.
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 flexibilility 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.
In another embodiment of the present invention, the results of which are illustrated in
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.
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.
In another embodiment, illustrated in
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).
Generally, in the embodiment shown in
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 μm 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.
Saftey Study
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 microsopy. 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.
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.
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.
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