In children, a self-correcting mechanism adjusts the growth of the eye so that the light-sensitive retina is located where images of the visual world are focused (the focal plane), producing clearly-focused vision (“emmetropia”). This mechanism uses visual cues to determine if the eye is too short (hyperopia) or has grown too long (myopia) relative to the focal plane and adjusts eye growth to move the retina back to emmetropia. However, in about 40% of people in the US, this mechanism allows the eyes to become too long so they are myopic (nearsighted). Even low amounts of myopia raise the risks of developing retinal holes or tears, retinal detachment, choroidal degeneration, glaucoma, cataract and other potentially blinding conditions caused by the elongated eye. Current treatments aimed at preventing or slowing the development of myopia have achieved only modest success.
Myopia (nearsightedness) is an enormous problem around the world, affecting perhaps more than 1 billion people worldwide. In myopia, the length of the eye is longer than optimal. Because myopia increases the risk for many retinal diseases, it is a leading cause of blindness worldwide. The economic cost of glasses, contact lenses, and refractive surgery is many millions of dollars in the US alone. However, these treatments do not remove the risk of blindness because they do not alter the length of the eye so it remains long. Myopia typically develops and increases (progresses) in childhood between the ages of 5 and 15. Slowing myopia development will require treatment throughout this extended period and thus must be safe in long-term use. Many companies are trying to develop effective ways to prevent children from developing myopia, or to slow the rate of myopia development so as to reduce the final amount in adulthood. Success using optical (contact lenses, glasses, wavelength filters) or pharmaceutical (eye drops) approaches has been limited. An effective, safe, non-invasive, non-pharmacological treatment that could be used in the home over many years would be of benefit to millions of people.
The eye of humans and, indeed, all vertebrates, is a globe with a clear tissue at the front, the cornea, through which light enters the eye. As shown in
For visual images to appear clear (not blurred) the axial length of the eye must position the retina at the focal plane. If the axial length is short relative to the focal plane (
At birth, most human and animal eyes are hyperopic because the axial length is short relative to the focal plane (
Light is detected because it is absorbed by the photopigments of the cones, the sensory cells in the retina. As shown in
There also are two additional photopigments in the retina: rhodopsin in the low-light sensitive rods, and melanopsin in the intrinsically photosensitive retinal ganglion cells. However, these two pigments are not thought to be important for high-acuity vision in bright light. Also, most humans have a third middle-wavelength sensitive (MWS) cone photopigment. The peak of the MWS absorbance is close to that of the LWS photopigment and the profile of the MWS photopigment overlaps extensively with that of the LWS cones. Dichromatic humans that, like the tree shrew, only have two photopigments, emmetropize normally. Without wishing to be bound by any hypothetical model, for the purposes of emmetropization, it is believed that the human system is essentially the same as for tree shrews using cone photopigments that absorb at long, versus short wavelengths and predict that the model and the experimental results from tree shrews will generalize to humans.
As noted, outdoor lighting, and most indoor lighting, contain many wavelengths. The eye focuses different wavelengths (colors) of light (long wavelength/red, and short wavelength/blue) at different distances behind the cornea. Blue wavelengths (
In recent years, both pharmacological and optical treatments have been examined and show promise for slowing, but not eliminating, axial elongation and myopia in children. However, pharmacological treatments involve daily use of eye drops in children. The effectiveness and safety of these over extended years of use has not been examined. Current optical treatments with spectacle and/or contact lenses have shown only limited slowing of myopia progression. Compliance: actually wearing the contacts or using the eye drops, has been a problem; so has drop-out (stopping treatment).
There is a need in the art for non-invasive methods to encourage emmetropization and discourage myopia, especially in the developing eyes of children.
A new design of multi-focal lens is disclosed where the different zones of the lenses have different color tints. A method is disclosed of altering the color filtering properties of the different focal zones of a multifocal contact or spectacle lens for myopia control. Multi-spectral multi-focal lenses should be readily manufacturable, as either contact lenses or spectacle lenses, and should also be readily tolerated by children (because the human perceptual visual system is remarkably tolerant of spatial mis-localization of color signals).
In a first aspect, a method of improving emmetropization in an eye is provided, said eye having a short-wavelength focal plane and a long-wavelength focal plane relatively farther from the cornea than the short-wavelength focal plane, the method comprising: adjusting the vision in the eye to achieve one or both of increasing the distance between the long-wavelength focal plane and the short wavelength focal plane; and positioning the short wavelength focal plane closer to the cornea than it would normally be located.
In a second aspect, a method of reducing or eliminating the development of myopia in an eye of a subject is provided, said eye having a short-wavelength focal plane and a long-wavelength focal plane relatively farther from the cornea than the short-wavelength focal plane, the method comprising: adjusting the vision in the eye to achieve one or both of increasing the distance between the long-wavelength focal plane and the short wavelength focal plane; and positioning the short wavelength focal plane closer to the cornea than it would normally be located.
In a third aspect, a vision correction device is provided that is configured to be worn by a human subject, the device comprising: a first focal zone of a more positive dioptric power and tinted to absorb relatively less visible light at the short end of the visible spectrum; and a second focal zone of a more negative dioptric power than the first focal zone, and tinted to absorb relatively more visible light at the short end of the spectrum than the first focal zone.
In a fourth aspect, a method of improving emmetropization in an eye is provided, said eye having longitudinal chromatic aberration, so short-wavelengths focus closer to, and long-wavelengths focus relatively farther from the cornea, the method comprising: adjusting the vision in the eye to achieve one or both of increasing the distance between the long-wavelength focal plane and the short wavelength focal plane; and positioning the short wavelength focal plane closer to the cornea than it would normally be located.
In a fifth aspect, a vision correction device is provided that is configured to be worn by a human subject, the device comprising: a first focal zone that provides a clear image on the fovea in myopes; a second focal zone of a more positive dioptric power and tinted to absorb relatively less visible light at the short end of the visible spectrum compared to the first focal zone; and a third focal zone of a more negative dioptric power than the first focal zone, and tinted to absorb relatively more visible light at the short end of the spectrum than the first focal zone.
In a sixth aspect, a vision correction device is provided that is configured to be worn by a human subject, the device comprising: a first zone that absorbs relatively less visible light at the short end of the visible spectrum; and a second focal zone that absorbs relatively more visible light at the short end of the spectrum than the first focal zone and configured to diffuse visible light.
The above presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key or critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art of this disclosure. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Well known functions or constructions may not be described in detail for brevity or clarity.
The terms “about” and “approximately” shall generally mean an acceptable degree of error or variation for the quantity measured given the nature or precision of the measurements. Typical, exemplary degrees of error or variation are within 20 percent (%), preferably within 10%, more preferably within 5%, and still more preferably within 1% of a given value or range of values. Numerical quantities given in this description are approximate unless stated otherwise, meaning that the term “about” or “approximately” can be inferred when not expressly stated.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The terms “first”, “second”, and the like are used herein to describe various features or elements, but these features or elements should not be limited by these terms. These terms are only used to distinguish one feature or element from another feature or element. Thus, a first feature or element discussed below could be termed a second feature or element, and similarly, a second feature or element discussed below could be termed a first feature or element without departing from the teachings of the present disclosure.
Terms such as “at least one of A and B” should be understood to mean “only A, only B, or both A and B.” The same construction should be applied to longer list (e.g., “at least one of A, B, and C”).
The term “consisting essentially of” means that, in addition to the recited elements, what is claimed may also contain other elements (steps, structures, ingredients, components, etc.) that do not adversely affect the operability of what is claimed for its intended purpose as stated in this disclosure. This term excludes such other elements that adversely affect the operability of what is claimed for its intended purpose as stated in this disclosure, even if such other elements might enhance the operability of what is claimed for some other purpose.
Methods and Devices
A model has been developed of how the self-correcting emmetropization mechanism uses wavelength cues to control the refractive state of the human eye. Based on this model, lenses have been designed to prevent or slow myopia development in children.
From the results of studies in tree shrews (animals closely related to primates), a model has been developed of how the combination of the wavelengths of light and optical defocus regulate eye growth. This model predicts that using multifocal lenses where the more positive zones are tinted blue and the less positive (e.g., zero power) zones are tinted yellow or clear, will stabilize refractive development and prevent or slow myopia development in children.
It has been found that the emmetropization mechanism uses some aspect of LCA to maintain the axial length within a narrow range. If the blue wavelengths are in focus (
A method of influencing the development of the eye is provided. The method comprises adjusting the vision in the eye to either move a long-wavelength focal plane away from a short-wavelength focal plane in the eye (or vice versa), or to move the short wavelength focal plane closer to the cornea. Of course, the method could achieve both effects (increasing the distance between the two focal planes and moving the short wavelength focal plane closer to the cornea). The method could find various uses. Some embodiments of the method may be used to improve emmetropization; in some such embodiments the method may be performed on a subject in need of improvement of emmetropization. Some embodiments of the method may be used to reduce or eliminate the development of myopia in an eye of the subject. In such embodiments the method may be performed on a subject in need of such reduction or elimination of the development of myopia.
The two focal planes (short wavelength and long wavelength) are defined by the relative wavelengths of light that form a focused image on each (i.e., the wavelength at the short focal plane is shorter than the wavelength at the long focal plane). In some embodiments of the method the shorter wavelength is somewhere in the range of green to blue. In further embodiments of the method the longer wavelength is somewhere in the range of green to red. In further embodiments, the longer wavelength is 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, at least any of the foregoing values, or a range between any two of the foregoing values. In further embodiments, the shorter wavelength is 550 nm, 540 nm, 530 nm, 520 nm, 510 nm, 500 nm, 490 nm, 480 nm, 470 nm, 460 nm, 450 nm, 440 nm, 430 nm, 420 nm, 410 nm, 400 nm, 390 nm, 380 nm, up to any of the foregoing values, or a range between any two of the foregoing values. In still further embodiments, the short-wavelength focal plane is predominantly blue. In still further embodiments, the long-wavelength focal plane is predominantly red.
The locations of the focal planes may be varied to achieve various desired effects. In a specific embodiment the long-wavelength focal plane is in focus on the retina. This is believed to encourage proper emmetropization and avoid the development of myopia.
A vision correction device 100 is disclosed that works by the same principles. It may be configured to be worn by an animal subject, including a human subject. The device 100 comprises two zones of different dioptric power and of different tints. A first focal zone 110 may be present of a more positive dioptric power and tinted to absorb relatively less visible light at the short end of the visible spectrum; and a second focal zone 120 may be present of a more negative dioptric power than the first focal zone 110, and tinted to absorb relatively more visible light at the short end of the spectrum than the first focal zone 110.
In
In embodiment of the device 100 in which the subject has myopia, the dioptric power of the second focal zone 120 may be sufficient to correct the myopia. The dioptric power differential in some embodiments is at least +0.25 (i.e., the first focal zone's dioptric power is at least +0.25 diopters greater than the second focal zone's dioptric power). In further embodiments of the device 100 the differential is about +0.5 to +3.0. In a specific embodiment of the device 100 the differential is about +2.0.
The first focal zone 110 may be tinted to absorb relatively less visible light than the second focal zone 120 below a certain “spectral cutoff” wavelength but absorb relatively more visible light than the second focal zone 120 above the cutoff wavelength. In some embodiments the spectral cutoff is equal to or less than a point between 420 nm and 560 nm. The differential tinting between the focal zones can be manifest in various color patterns. In some embodiments the first focal zone 110 is tinted blue. In some embodiments the second focal zone 120 is tinted clear or yellow. The focal zones may have various geometric patterns. In a preferred embodiment the first focal zone 110 is either circular or annular, and the second focal zone 120 is either circular or annular and is concentric with the first focal zone 110 (
Further embodiments of the device 100 may comprise at least one additional focal zone 130, the additional focal zone 130 being about equal to the first focal zone 110 or the second focal zone 120 in tint and dioptric power. More focal zones may be present, each being about equal in tint and dioptric power to either: the first focal zone 110 or the second focal zone 120. The multiple additional zones may be placed in an alternating pattern between zones equal in tint and dioptric power to the first focal zone 110 and zones equal in tint and dioptric power to the second focal zone 120.
In an alternative embodiment of the device 100, one of the zones diffuses transmitted light, and has a transmission spectrum that is relatively shorter than the other. Some such embodiments of the device 100 comprise a first zone 110 that passes wavelengths longer than a cutoff value and are optically clear (not diffusive); and a second zone 120 that passes wavelengths shorter than the cut value and degrade the image (e.g., by diffusing transmitted light). The spectral cutoff point may be any that is disclosed above as suitable for use in other embodiments of the device 100. A further embodiment comprises an optically clear zone tinted or otherwise filtered to pass longer wavelengths, and an optically diffuse zone tinted or otherwise filtered to pass shorter wavelengths. A still further embodiment comprises an optically clear zone having no color filtering or tinting; and an optically diffuse zone filtered or tinted to pass short wavelengths. A still further embodiment comprises an optically clear zone filtered or tinted to pass long wavelengths; and an optically diffuse zone having no color filtering or tinting. These variants are expected to achieve relatively high retinal image contrast for long wavelengths, but relatively reduced retinal image contrast for short wavelengths. It is believed this will be interpreted by the retina as a sign that the eye is too long and that it should stop growing (i.e., it would be anti-myopiagenic). These variants are expected to have the advantages of ease of production and effectiveness over a large range of defocus. In some embodiments of the method the shorter wavelength is somewhere in the range of green to blue. In further embodiments of the method the longer wavelength is somewhere in the range of green to red. In further embodiments, the longer wavelength is 560 nm, 570 nm, 580 nm, 590 nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680 nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, at least any of the foregoing values, or a range between any two of the foregoing values. In further embodiments, the shorter wavelength is 550 nm, 540 nm, 530 nm, 520 nm, 510 nm, 500 nm, 490 nm, 480 nm, 470 nm, 460 nm, 450 nm, 440 nm, 430 nm, 420 nm, 410 nm, 400 nm, 390 nm, 380 nm, up to any of the foregoing values, or a range between any two of the foregoing values. In still further embodiments, the short-wavelength focal plane is predominantly blue. In still further embodiments, the long-wavelength focal plane is predominantly red.
Embodiments of the multi-focal multi-spectral lenses may be effective, safe for long-term use, non-invasive, simple to use (promoting compliance with treatment) and/or combinable with other anti-myopia treatments.
The claimed subject matter can be further understood by reference to the following prophetic example.
A feedback mechanism operates in growing post-natal eyes that uses optical cues to regulate the eye's axial elongation rate so as to achieve focus by matching the location of the retina to the focal plane, a process termed emmetropization. It is believed that refractive error contains the cues that guide the mechanism. The target of the emmetropization mechanism is minimal defocus (actually, low hyperopia easily cleared with accommodation). Hyperopic defocus (retina closer to the cornea than the focal plane) creates retinal signals (a “drive”) that increases the axial elongation rate, moving the retina to where light is in focus. Myopic defocus (retina behind the focal plane) produces a drive to slow axial elongation so that the maturing optics move the focal plane to the retina. When the refractive state reaches the target, the drive to increase or decrease axial elongation is zero.
The emmetropization mechanism evolved and normally operates in broadband (“white”) light where all wavelengths are present across the visible spectrum (400-700 nm). In broadband light, many cues are present in a defocused image that potentially can provide the drive that generates retinal signals used to modulate axial elongation. For example, in a defocused eye, image contrast on the retina is reduced. The retinal image produced by a sharp light-dark edge becomes a more gradual change from higher to lower illuminance across the retina. Other cues, such as high spatial frequencies, higher order-aberrations (astigmatism, coma, etc.) and other possible cues are also altered. The specific optical cues used by the emmetropization mechanism share the basic premise that the retina doesn't specifically detect “defocus”; rather it detects changes in the “image statistics” (such as image contrast) across the retinal surface that are produced by defocus.
Another optical cue produced by defocused images involves LCA. Vertebrate eyes have significant LCA: long wavelengths focus farther away from the cornea than do shorter wavelengths, generally on the order of 2 to 3 Diopters (D) across the visible range. Therefore, when longer wavelengths are in better relative focus than shorter wavelengths (an indication that the eye is longer than optimal), this may provide a signal that the eye is too long and generate retinal signals that restrain axial elongation. If shorter wavelengths are in better focus than long wavelengths, this may lead to retinal signals that increase axial elongation.
In a direct assessment to determine if LCA cues are important for emmetropization, chicks were exposed to simulations of the chromatic signals expected from hyperopic and myopic defocus, and it was found that the eyes could interpret these chromatic signals appropriately. Another way to assess if LCA provides important cues for the emmetropization mechanism is to place young animals in an environment where there is no LCA by housing them in narrow band illumination, so that it is impossible to compare image statistics at different wavelengths. If LCA cues are important, removing them should impair the ability of the emmetropization mechanism to function. Although there is a high degree of variability in the results of these studies by species and the specific wavelengths used, the evidence indicates that emmetropization is disrupted in narrow band-width light in tree shrews, non-human primates, chicks, guinea pigs and mice. Studies suggest that the LCA cues present in broadband lighting conditions are not only important for normal operation of the emmetropization mechanism, but also are essential for it to function properly. When LCA cues are removed, the emmetropization mechanism is unable to utilize other, remaining, defocus-related cues to maintain or achieve emmetropia.
Tree shrews, like most mammals, are dichromats. Tree shrew retinas contain a cone photoreceptor type sensitive to shorter wavelengths (SWS—encoded by the OPN1SW gene, peak sensitivity in tree shrews is approximately 428 nm) and another cone type sensitive to longer wavelengths (LWS—encoded by the OPN1LW gene, peak sensitivity is approximately 555 nm) (
Without wishing to be bound by any hypothetical model, it is proposed that the two arrays of cone photoreceptors independently detect “image sharpness” and have opponent effects on axial growth of the eye. If the SWS cone array detects sharper images on the retina than the LWS system, post-receptoral retinal circuitry then signals for increased axial growth (a positive drive). If the LWS cone array detects relatively sharper images on the retina, the post-receptoral circuitry then signals for slower axial growth (a negative drive).
A model is provided of how the retinal image, as sensed separately by the SWS and LWS cones, varies as a function of both defocus and the spectrum of ambient light. It can be determined if the difference between the SWS and LWS images can plausibly distinguish between hyperopic and myopic defocus over a physiological range of values, given the known spacing of the SWS and LWS cone arrays in tree shrews, and predictions can be made about how changes in the shape of the spectrum of ambient light could affect emmetropization.
The development and implementation of the model involves several steps. For a given spectrum of light, and a given position of the retina relative to the optics:
(1) Calculate the size of the circular disk of light (“blur disk”) created by a single point at optical infinity, for all wavelengths in 10 nm steps.
(2) At each wavelength, weight the intensities of the bur disks by the intensity of the light, the area of the blur disks, and the absorbance of both the SWS and LWS cones.
(3) Combine all the blur disks to produce a separate “point spread function” for the SWS and the LWS cones.
(4) Use the point spread functions to calculate the effective spatial luminance profile of the retina, in response to a black/white edge, for the SWS and for the LWS cones.
(5) Use these luminance profiles to calculate a single number, a spectral drive, which reflects the difference in image sharpness between the SWS and LWS cones and the direction of the effect on axial growth (increase or decrease).
The model can then be applied in several different lighting conditions.
(6) Use the point spread functions to calculate the effective spatial luminance profiles on the retina, in response to a naturalistic grayscale image, for the SWS and LWS cones.
(7) In addition, the results of [6] are used to calculate the mean spatial frequency distribution of the responses of the SWS and LWS cones to an entire naturalistic grayscale image.
Because the emmetropization mechanism acts by changing the axial length of the eye (and thereby the position of the retina) and does not appear to alter the optics of the eye, in the chosen model the optics are held fixed and different amounts of defocus (blur conditions) are simulated by changing the location of the retina with respect to the optimal focus point of a 550 nm light. Retinal positions closer to the posterior principal plane simulate hyperopic defocus; locations farther away from the posterior principal plane simulate myopic defocus.
In the model, the effects of diffraction and higher-order monochromatic aberration are ignored. All referenced simulations use custom routines written in Matlab version R2017b.
(1) Calculate the size of the circular disk of light (“blur disk”) created by a single point at optical infinity, for all wavelengths in 10 nm steps.
As illustrated in
In the model, it can be assumed that tree shrew eyes have 2.77 Diopters (D) of LCA between 428 and 555 nm and that the point of best focus changes linearly with wavelength. Although not strictly true, the curves of LCA versus wavelength are smoothly monotonic across the range of visible light, so it was taken as a simplifying assumption. Thus, the point of best focus shifts away from the posterior principal plane by 8.7 μm (approximately 0.26 D in a tree shrew eye) for every 10 nm increase in the wavelength of light.
Fl
actual=5810+(λ550)*0.87
where Flactual is the actual focal length at a wavelength of A nm. To model the image of a light-dark edge on the retina, the effects on image focus of changing the wavelength across the spectrums need to be calculated at each retinal position. As illustrated in
coc=abs(((flactual−retinapos)/flactual)*3000)
where coc is the diameter of the circle of confusion, and retinapos is the position of the retina in nm relative to the optics. The pupil diameter is assumed to be 3,000 μm.
(2) At each wavelength, weight the intensities of the blur disks by the intensity of the light, the area of the blur disks, and the absorbance of both the SWS and LWS cones.
Assuming that, at each wavelength, the coc defines a circular “blur disc” of uniform intensity (
As illustrated in
As illustrated in
(3) Combine all of the blur disks to produce a separate “point spread function” for the SWS and the LWS cones.
As illustrated in
(4) Use the point spread functions to calculate the effective spatial luminance profile on the retina, in response to a black/white edge, for the SWS and for the LWS cones.
Natural images are full of extended edges, and, unlike isolated points, these extended edges can be robustly detected by retinal neurons even when blurred. Emmetropization might not be specifically driven by extended edges, but a simplified visual stimulus can be used to gain insight into how different levels of hyperopic and myopic blur could be translated into different activation patterns of the SWS and LWS cone arrays. This process is schematized in
(5) Use these luminance profiles to calculate a single number, a spectral drive, which reflects the difference in image sharpness between the SWS and LWS cones and the direction of the effect length (increase or decrease).
The process can be repeated separately for the SWS and LWS cones, and for a range of retinal positions from hyperopic to myopic, as shown in
The blur profile for each cone type can be normalized to span the range between 0 and 1. It is established that cone photoreceptors can adapt to a wide range of light levels, and the post-receptoral retinal circuitry could also work to normalize the processing of these signals. It is unknown exactly how much the normalization of cone responses is or is not important for emmetropization, but using normalized responses can be a reasonable starting assumption.
The model may be applied to different artificial ambient lighting spectra, including, but not limited to, broad-spectrum “white” light, narrow band blue combined with narrow-band red, narrow-band red or narrow-band blue alone, limited-bandwidth green+blue, colony fluorescent light, the red+green+blue light from a computer screen, and a hypothetical multi-spectral multi-focal lens.
(6) Use the point spread functions to calculate the effective spatial luminance profiles on the retina, in response to a naturalistic grayscale image, for the SWS and LWS cones.
While natural images are dominated by lower spatial frequencies, it is understood that the real world consists of more than simple step edges. Therefore, the model should be extended to natural images. A black and white image can be convolved with the point spread functions for the SWS and LWS cones separately. This results in a model of the 2D spatial pattern of effective illuminance across the retina as sampled by the SWS and LWS cones. These images can be normalized to have the same minimum and mean value across the entire image. The radially averaged Fourier transform can be applied across these patterns, using the method derived from, and plotted the direction-averaged power as a function of spatial frequency. In the model, the possible effect of different color objects in the environment should be ignored, and a purely black and white world should be assumed. As most objects in the world are not brightly colored, and as the emmetropization system must average over a large number of image patches, an assumed black and white world is a reasonable approximation for this level of modeling.
(7) In addition, use the results of (6) to calculate the mean spatial frequency distribution of the responses of the SWS and LWS cones to an entire naturalistic grayscale image.
Although the activity of the retina that is important for perception and for the visual guidance of behavior is driven by what is on the retina moment-by-moment, emmetropization averages over a considerable period of time. Primates will typically make on the order of three saccades per second, and for retinal locations not on or near the fovea (which is most of the retina), any given patch of the retina will receive on the order of 10,000 random samplings of the visual world per hour. Tree shrews do not make large saccades, but they do routinely make head movements with similar frequency as primates make saccades, so the effect on retinal stimulation should be similar. Therefore, the effect of a complex naturalistic image on emmetropization, can be approximated by averaging the image statistics across the entire image.
As the retinal position is moved away from the posterior principle plane, the shape of the illuminance profiles changes. At the most hyperopic retinal position (5670 μm), the SWS profile has a steeper slope than the LWS illuminance profile, indicating that the light-dark edge was in sharper focus for the SWS cones. As the retina moves away from the posterior principle plane the slope of the SWS illuminance profile becomes lower, indicating that the edge was more blurred as viewed by the SWS cone array. In contrast, at locations farther away from the posterior principle plane, the slope of the LWS illuminance profile becomes steeper. The sharpest SWS profile (at 5730 μm) is sharper than the sharpest LWS profile (at 5810 μm) because the SWS cones have a relatively narrow bandwidth and the LWS cones have a much broader bandwidth, as illustrated in
The disclosed simulations did not find any broad spectrum of light that would either significantly bias emmetropization towards hyperopia, or increase the magnitude of the drive.
Although the visual world contains many abrupt luminance edges, it also contains complex luminance changes.
Tree shrews have with a nominal visual behavioral acuity of approximately 2 to 3 cycles/degree presumably mediated by the array of LWS cones. The LWS cones have a typical inter-cone separation of approximately 6 μm across the retina, but the SWS cones have a relatively constant SWS to SWS cone spacing of 18 μm. Thus, the limiting factor for resolving differential image sharpness at long vs. short wavelengths, will be the spacing of the SWS cones. This spacing would give a spatial Nyquist frequency for the SWS array of approximately 3 cycles/degree. As illustrated in
That the emmetropization mechanism detects image contrast and adjusts axial growth of the eye to maximize image contrast is a familiar concept. A dual-detector spectral drive model was developed using data from the dichromatic mammal, tree shrew. In the disclosed model, image sharpness can be detected by two independent imaging arrays, comprised of the SWS and the LWS cones. In broadband lighting conditions, because of longitudinal chromatic aberration, the two imaging arrays cannot both simultaneously maximize image sharpness. If image sharpness (as detected by the SWS cone array contrast) is greater than that as detected by the LWS cone array, a drive is generated that increases axial growth. If image contrast is greater as detected by the LWS cone array, an opposing drive is generated that slows axial growth. The target is a retinal location where the image contrast is intermediate and an proximately equal in both cone arrays.
Although the emmetropization mechanism exists to achieve and maintain good focus, the model, does not use “optical defocus” as the primary cue. Instead, the model depends on the difference in the image statistics as sampled by the SWS and LWS cone arrays. Under a broadband spectrum of lighting, this mechanism efficiently homes in on good focus. However, when the spectrum of light is significantly altered, shifting the target of the spectral drive, the emmetropization mechanism can become maladaptive producing a stable refractive state that is different from emmetropia, despite defocus cues.
When the response to a monochromatic 2D image was modeled for a physiologically relevant range of defocus, it was be found, as illustrated in
According to the model, the emmetropization mechanism should be able to accurately use differential wavelength cues in all but the most distorted light spectra, as long as the spectra span a broad band of wavelengths and have more than two peaks. Spectra consisting of narrow band red and narrow band blue light together produce a target that is myopic, but we were unable to find a light spectrum (other than narrow band red) that could significantly either shift the target in the direction of hyperopia, or increase the magnitude of the drive signal. Simulations suggest such a result could only be achieved in broadband light by manipulating the effective magnitude of LCA, for example, by using multifocal lenses with different spectral filtering in the different optical zones (
The model only examines information available at the level of the photoreceptors, and ignores the considerable processing that occurs as information passes through the bipolar, horizontal, amacrine and ganglion cells. However, the retinal circuitry cannot create information that is not present in the spatial pattern of light across the photoreceptors. The information available at the photoreceptor level, as modeled, appears to be sufficient to provide signals to subsequent retinal stages that account for the behavior of the emmetropization mechanism in both broadband and various narrow-band ambient lighting of differing peak wavelengths.
Given the evolutionary importance of in-focus images to survival, it is not surprising that defocus, as detected by the dual detector spectral drive model is not the only cue used by the emmetropization mechanism. When tree shrews and macaque monkeys housed in narrow-band red light have also worn plus-power (macaque) or minus power lenses (tree shrew), the lenses alter the refractive responses in the appropriate direction, increasing the hyperopia in macaques and increasing the myopia in tree shrews. These results emphasize that the emmetropization mechanism utilizes multiple cues related to defocus. In narrow-band light the spectral cues appear to be stronger than the defocus cues and prevent achieving or maintaining emmetropia.
Even if a dual detector spectral drive system guides emmetropization, it is not clear how the strength of the drive signal (Y-axis as shown in
It is important to note that the spectra used to examine the effects of wavelength on emmetropization in the tree shrews used in the model were produced either by fluorescent lamps or by light emitting diodes, not by digital monitors. The effects of wavelength on emmetropization cannot be modeled using standard “red-green-blue” digital images because focus varies continuously with wavelength. For example, as regards a single photoreceptor, a dim light of a wavelength at the optimal frequency cannot be distinguished from a brighter light at a less optimal wavelength that produces the same photon catch. This is the basis of color metamerism, and is why the video display technology used in this model works with just red, green, and blue light emitting elements. However, as regards emmetropization, these two conditions are not equivalent, because the degree of focus will be different. Thus, an analysis of the effects of wavelength on emmetropization must integrate across all wavelengths, a procedure known as hyperspectral imaging.
Unlike tree shrews, many primates, including most humans, are trichromats, with middle wavelength sensitive (MWS) cones added to the SWS and LWS cones present in dichromatic species. However, it is suggested that the principles of the spectral drive model would apply in trichromatic species if the MWS and the LWS cone arrays both together provide a signal to the emmetropization mechanism that opposes the signal provided by the SWS cone array (similar to the blue-yellow interaction found in chromatically-sensitive retinal ganglion cells). The peak wavelength sensitivities for the MWS and LWS cones, in humans, are very close: 530 and 560 nm. These are far removed from the 420 nm peak for the human SWS cones. Also, the LCA curve is nonlinear; focus changes more rapidly with increasing wavelength at shorter than, at longer, wavelengths. In humans, the difference in where light is focused between the MWS and LWS cones is approximately 0.1 D. The difference in where light is in focus between the short wavelength versus the medium and long wavelength cones is approximately 1.0 and 1.1 D, respectively. Thus, there is relatively little difference in the information about focus available to the MWS in comparison to the LWS cones, but a substantial difference between the SWS short and either or both of the MWS and LWS cones. It is suggested that it is the difference between the image contrasts on the SWS system as compared to the longer (MWS & SWS) systems that is involved in emmetropization. This suggestion is supported by the fact that emmetropization occurs in many dichromatic species and in dichromatic humans. The evolution of trichromacy did not disrupt the emmetropization mechanism.
In humans high-acuity visual perception is mediated by the LM cone midget system in the fovea, but it has been demonstrated that emmetropization is controlled, or strongly influenced, by the peripheral visual field. In the peripheral retina, there is no midget system and L/M cones are much sparser than in the fovea. It may also be relevant that, as images are placed on differing retinal locations, from the central to the peripheral visual field, the ability of human subjects to discriminate long (yellow) versus short (blue) wavelengths is maintained, but the ability to discriminate green versus red is lost except perhaps for very large stimuli, making the periphery essentially dichromatic. These results of the model suggest that the red-green contrast may be less important for emmetropization than the blue-yellow. The way in which the emmetropization mechanism uses visual cues (which may not be conveyed to central structures) may not always match up with what is observed in centrally-mediated visual perception, but the model's findings still suggest that it is the long versus short wavelength comparison that is crucial for emmetropization, even in trichromatic primates. As long as the combined L+M cone mosaic is at least as spatially dense as the S cone mosaic, then according to the model, it is functionally irrelevant whether the L+M cones are or are not more densely spaced than the S cones.
The developed model, using an opponent dual-detector spectral drive system, utilizes longitudinal chromatic aberration to guide normal emmetropization in dichromatic tree shrews and perhaps in tri-chromatic species such as humans. The existence of a dual-detector mechanism could help to distinguish myopic from hyperopic defocus at the retinal level, and provides an explanation why continuous exposure to some narrow-band lighting conditions could produce deviations from emmetropia in tree shrews and, perhaps in humans.
In addition to anything described above or currently claimed, it is specifically contemplated that any of the following embodiments may be claimed.
Embodiment 1. A method of improving emmetropization in an eye, said eye having a short-wavelength focal plane and a long-wavelength focal plane relatively farther from the cornea than the short-wavelength focal plane, the method comprising: adjusting the vision in the eye to achieve one or both of increase the distance between the long-wavelength focal plane and the short wavelength focal plane; and position the short wavelength focal plane closer to the cornea than it would normally be located.
Embodiment 2. A method of reducing or eliminating the development of myopia in an eye of a subject, said eye having a short-wavelength focal plane and a long-wavelength focal plane relatively farther from the cornea than the short-wavelength focal plane, the method comprising: adjusting the vision in the eye to achieve one or both of increase the distance between the long-wavelength focal plane and the short wavelength focal plane; and position the short wavelength focal plane closer to the cornea than it would normally be located.
Embodiment 3. The method of any one of embodiments 1-2, wherein the method comprises both of: increasing the distance between the long-wavelength focal plane and the short wavelength focal plane; and positioning the short wavelength focal plane closer to the cornea than it would normally be located.
Embodiment 4. The method of any one of embodiments 1-3, wherein the short-wavelength focal plane is predominantly blue.
Embodiment 5. The method of any one of embodiments 1-4, wherein the long-wavelength focal plane is predominantly red.
Embodiment 6. The method of any one of embodiments 1-5, wherein the long-wavelength focal plane is in focus on the retina.
Embodiment 7. The method of any one of embodiments 1-6, comprising providing a vision correction device comprising: a first focal zone 110 of a more positive dioptric power and tinted to absorb relatively less visible light at the short end of the visible spectrum; and a second focal zone of a more negative dioptric power than the first focal zone 110, and tinted to absorb relatively more visible light at the short end of the spectrum than the first focal zone 110.
Embodiment 8. A vision correction device that is configured to be worn by a human subject, the device comprising: a first focal zone of a more positive dioptric power and tinted to absorb relatively less visible light at the short end of the visible spectrum; and a second focal zone of a more negative dioptric power than the first focal zone, and tinted to absorb relatively more visible light at the short end of the spectrum than the first focal zone.
Embodiment 9. The method or device of any one of embodiments 7-8, wherein the subject has myopia, and wherein the dioptric power of the second focal zone is sufficient to correct the myopia.
Embodiment 10. The method or device of any one of embodiments 7-Embodiment 9, wherein the first focal zone's dioptric power is at least +0.25 diopters greater than the second focal zone's dioptric power.
Embodiment 11. The method or device of any one of embodiments 7-10, wherein the first focal zone's dioptric power is about +0.5 to +3.0 diopters greater than the second focal zone's dioptric power.
Embodiment 12. The method or device of any one of embodiments 7-11, wherein the first focal zone's dioptric power is about +2.0 diopters greater than the second focal zone's dioptric power.
Embodiment 13. The method or device of any one of embodiments 7-12, wherein the first focal zone is tinted to absorb relatively less visible light equal to or less than a spectral cutoff point between 420 nm and 560 nm wavelength, and absorb relatively more visible light above said spectral cutoff point.
Embodiment 14. The method or device of any one of embodiments 7-13, wherein the second focal zone is tinted to absorb relatively more visible light equal to or less than a spectral cutoff point between 420 nm and 560 nm wavelength, and absorb relatively less of the visible light above said spectral cutoff point.
Embodiment 15. The method or device of any one of embodiments 7-14, wherein the first focal zone is tinted blue.
Embodiment 16. The method or device of any one of embodiments 7-15, wherein the second focal zone is tinted clear.
Embodiment 17. The method or device of any one of embodiments 7-16, wherein the second focal zone is tinted yellow.
Embodiment 18. The method or device of any one of embodiments 7-17, wherein the first focal zone is either circular or annular, and wherein the second focal zone is either circular or annular and is concentric with the first focal zone.
Embodiment 19. The method or device of any one of embodiments 7-18, wherein the corrective device comprises: at least one additional focal zone, the additional focal zone being about equal to the first focal zone in tint and dioptric power.
Embodiment 20. The method or device of any one of embodiments 7-19, wherein the corrective device comprises: at least one additional focal zone, the additional focal zone being about equal to the second focal zone in tint and dioptric power.
Embodiment 21. The method or device of any one of embodiments 7-20, wherein the corrective device comprises: multiple additional focal zones, each of the additional focal zones being about equal in tint and dioptric power to either: the first focal zone or the second focal zone.
Embodiment 22. The method or device of any one of embodiments 7-21, wherein said multiple additional zones occur in an alternating pattern between zones equal in tint and dioptric power to the first focal zone and zones equal in tint and dioptric power to the second focal zone.
Embodiment 23. The method or device of any one of embodiments 7-22, wherein: the first focal zone is either circular or annular; the second focal zone is either circular or annular and is concentric with the first focal zone; the device comprises a first group of additional focal zones being about equal in tint and dioptric power to the first focal zone, wherein each of the first group of additional focal zones is circular or annular and is concentric with the first focal zone; and the device comprises a second group of additional focal zones being about equal in tint and dioptric power to the second focal zone, wherein each of the second group of additional focal zones is circular or annular and is concentric with the first focal zone.
Embodiment 24. The method or device of any one of embodiments 7-23, wherein the device is one of a multifocal contact lens or multifocal spectacles.
Embodiment 25. A method of improving emmetropization in an eye of a subject, the method comprising equipping the subject with the vision correction device of any one of embodiments 7-24.
Embodiment 26. A method of reducing or eliminating the development of myopia in an eye of a subject, the method comprising equipping the subject with the vision correction device of any one of embodiments 7-25.
Embodiment 27. A vision correction device configured to be worn by a human subject, the device comprising: a first zone that absorbs relatively less visible light at the short end of the visible spectrum; and a second focal zone that absorbs relatively more visible light at the short end of the spectrum than the first focal zone and configured to diffuse visible light.
Embodiment 28. The vision correction device of embodiment 27, wherein the first zone absorbs relatively less visible light equal to or less than a spectral cutoff point between 420 nm and 560 nm wavelength, and the second zone 120s absorbs relatively more visible light equal to or less than said spectral cutoff point.
Embodiment 29. The vision correction device of any one of embodiments 27-28, wherein the first zone is tinted blue.
Embodiment 30. The vision correction device of any one of embodiments 27-29, wherein the second zone 120 is tinted clear.
Embodiment 31. The vision correction device of any one of embodiments 27-30, wherein the second zone 120 is tinted yellow.
Embodiment 32. The vision correction device of any one of embodiments 27-31, wherein one of the first or second zone 120s is formed by multiple dispersed areas, and wherein the other of the first or second zone 120s is an interstitial area between said multiple dispersed areas.
Embodiment 33. The vision correction device of any one of embodiments 27-32, wherein the first zone is either circular or annular, and wherein the second zone 120 is either circular or annular and is concentric with the first zone.
Embodiment 34. A method of improving emmetropization in an eye of a subject, the method comprising equipping the subject with the vision correction device of any one of embodiments 27-33.
Embodiment 35. A method of reducing or eliminating the development of myopia in an eye of a subject, the method comprising equipping the subject with the vision correction device of any one of embodiments 27-33.
It is to be understood that any given elements of the disclosed embodiments of the invention may be embodied in a single structure, a single step, a single substance, or the like. Similarly, a given element of the disclosed embodiment may be embodied in multiple structures, steps, substances, or the like.
The foregoing description illustrates and describes the processes, machines, manufactures, compositions of matter, and other teachings of the present disclosure. Additionally, the disclosure shows and describes only certain embodiments of the processes, machines, manufactures, compositions of matter, and other teachings disclosed, but, as mentioned above, it is to be understood that the teachings of the present disclosure are capable of use in various other combinations, modifications, and environments and is capable of changes or modifications within the scope of the teachings as expressed herein, commensurate with the skill and/or knowledge of a person having ordinary skill in the relevant art. The embodiments described hereinabove are further intended to explain certain best modes known of practicing the processes, machines, manufactures, compositions of matter, and other teachings of the present disclosure and to enable others skilled in the art to utilize the teachings of the present disclosure in such, or other, embodiments and with the various modifications required by the particular applications or uses. Accordingly, the processes, machines, manufactures, compositions of matter, and other teachings of the present disclosure are not intended to limit the exact embodiments and examples disclosed herein. Any section headings herein are provided only for consistency with the suggestions of 37 C.F.R. § 1.77 or otherwise to provide organizational queues. These headings shall not limit or characterize the invention(s) set forth herein.
This application cites the priority of U.S. Provisional Patent Application No. U.S. 62/902,817, filed on 19 Sep. 2019 (currently pending). The contents of U.S. 62/902,817 are incorporated herein by reference in their entirety.
This invention was made with government support under the National Eye Institute grant numbers R21EY025254, RO1 028578, and P30EY003909. The government has certain rights in the invention. In this context “government” refers to the government of the United States of America.
Filing Document | Filing Date | Country | Kind |
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PCT/US20/48788 | 8/31/2020 | WO |
Number | Date | Country | |
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62902817 | Sep 2019 | US |