Method and Apparatus for Limiting Growth of Eye Length Patent Application (2025)

U.S. patent application number 17/352570 was filed with the patent office on 2021-11-04 for method and apparatus for limiting growth of eye length. The applicant listed for this patent is The Medical College of Wisconsin, Inc.. Invention is credited to Jay Neitz, Maureen Neitz.

Method and Apparatus for Limiting Growth of Eye Length

Abstract

Certain embodiments of the present invention are directed totherapeutic intervention in patients with eye-length-relateddisorders to prevent, ameliorate, or reverse the effects of theeye-length-related disorders. Embodiments of the present inventioninclude methods for early recognition of patients witheye-length-related disorders, therapeutic methods for inhibitingfurther degradation of vision in patients with eye-length-relateddisorders, reversing, when possible, eye-length-related disorders,and preventing eye-length-related disorders. Additional embodimentsof the present invention are directed to particular devices used intherapeutic intervention in patients with eye-length-relateddisorders.

Related U.S. Patent Documents

Claims

1-5. (canceled)

6. A method, comprising: forming an ophthalmic lens comprising anarea having a plurality of elements selected from the groupconsisting of: (i) bumps on a surface of the ophthalmic lens; (ii)depressions on the surface of the ophthalmic lens; (iii)translucent inclusions in a lens material; and (iv) transparentinclusions in the lens material, the transparent inclusions havinga refractive index different from that of the lens material,wherein the elements are dot-shaped elements having, in the area ofthe ophthalmic lens, a non-zero dot density in a range between 0and 8 dots per mm.sup.2.

7. The method of claim 6, wherein the forming comprises obtainingan ophthalmic lens for a person identified as having aneye-lengthening disorder and introducing, to the area of theophthalmic lens, the plurality of elements.

8. The method of claim 6, wherein the non-zero dot density variesacross the area.

9. The method of claim 8, wherein the non-zero dot densityincreases in a radial direction from a central region of theophthalmic lens toward a periphery of the ophthalmic lens.

10. The method of claim 6, wherein the area continuously covers acentral region of the ophthalmic lens.

11. The method of claim 10, wherein the non-zero dot density variesacross the area.

12. The method of claim 11, wherein the non-zero dot densityincreases in a radial direction from the central region toward aperiphery of the ophthalmic lens.

13. The method of claim 6, wherein the area surrounds a second arealeft free of the elements.

14. The method of claim 13, wherein the second area is located at acentral region of the ophthalmic lens.

15. The method of claim 14, wherein the second area has a diameterless than 10 mm.

16. The method of claim 6, wherein the non-zero dot density variesacross the area.

17. The method of claim 16, wherein the non-zero dot densityincreases in a radial direction from a central region of theophthalmic lens toward a periphery of the ophthalmic lens.

18. The method of claim 16, wherein the area comprises a region inwhich the non-zero dot density is constant.

19. The method of claim 18, wherein the region is in a peripheralregion of the ophthalmic lens.

20. The method of claim 16, wherein the ophthalmic lens comprises acentral region, a peripheral region, and an intermediate regionbetween the central region and the peripheral region, and whereinthe non-zero dot density radially varies in the intermediateregion.

21. The method of claim 20, wherein the non-zero dot densityincreases monotonically across the intermediate region from thecentral region to the peripheral region.

22. The method of claim 6, wherein the plurality of elementsconsist entirely of bumps on a surface of the ophthalmic lens.

23. The method of claim 6, wherein the plurality of elements have adensity, dimension, and material selected to reduce a visual acuityin a patient's vision when looking through the area.

24. The method of claim 23, wherein the density, dimension, andmaterial of the plurality of elements in the area are selected toreduce a visual acuity from 20/20 when a line of sight of thepatient looking through the first lens passes through the secondarea to about 20/25 when the line of sight the patient passesthrough the first area.

25. The method of claim 6, further comprising providing a patientwith eyeglasses containing the ophthalmic lens.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation from U.S. patentapplication Ser. No. 17/008,167 filed on Aug. 31, 2020 and nowpublished as US 2020/0393699, which is a continuation from the U.S.patent application Ser. No. 16/385,810 filed on Apr. 16, 2019 andnow granted as U.S. Pat. No. 10,795,181, which is a continuationfrom the U.S. patent application Ser. No. 15/625,222 filed on Jun.16, 2017 and now granted as U.S. Pat. No. 10,302,962, which in turnis a continuation from U.S. patent application Ser. No. 13/141,161filed on Sep. 12, 2011 and now granted as U.S. Pat. No. 9,720,253,which is a US national phase from the International PatentApplication No. PCT/US2009/069078, filed on Dec. 21, 2009 andpublished as WO 2010/075319, which in turn claims priority from theU.S. Provisional Patent Application No. 61/139,938 filed on Dec.22, 2008. The disclosure of each of the above-identifiedapplications is incorporated herein by reference.

TECHNICAL FIELD

[0002] The present invention is related to treatment ofeye-length-related disorders, including myopia, to varioustherapeutic devices employed to treat patients witheye-length-related disorders, and to various methods and devicesfor generally controlling eye growth in biological organisms.

BACKGROUND

[0003] The eye is a remarkably complex and elegant optical sensorin which light from external sources is focused, by a lens, ontothe surface of the retina, an array of wavelength-dependentphotosensors. As with any lens-based optical device, each of thevarious shapes that the eye lens can adopt is associated with afocal length at which external light rays are optimally ornear-optimally focused to produce inverted images on the surface ofthe retina that correspond to external objects observed by the eye.The eye lens, in each of the various shapes that the eye lens canadopt, optimally or near-optimally, focuses light emitted by, orreflected from, external objects that lie within a certain range ofdistances from the eye, and less optimally focuses, or fails tofocus, objects that lie outside that range of distances.

[0004] In normal individuals, the axial length of the eye, ordistance from the lens to the surface of the retina, corresponds toa focal length for near-optimal focusing of distant objects. Theeyes of normal individuals focus distant objects without nervousinput to muscles, which apply forces to alter the shape of the eyelens, a process referred to as "accommodation." Closer, nearbyobjects are focused, by normal individuals, as a result ofaccommodation. Many people suffer from eye-length-relateddisorders, such as myopia, in which the axial length of the eye islonger than the axial length required to focus distant objectswithout accommodation. Myopic individuals view closer objects,within a range of distances less than typical distant objects,without accommodation, the particular range of distances dependingon the axial length of their eyes, the shape of their eyes, overalldimensions of their eyes, and other factors. Myopic patients seedistant objects with varying degrees of blurriness, again dependingon the axial length of their eyes and other factors. While myopicpatients are generally capable of accommodation, the averagedistance at which myopic individuals can focus objects is shorterthan that for normal individuals. In addition to myopicindividuals, there are hyperopic individuals who need toaccommodate, or change the shape of their lenses, in order to focusdistant objects.

[0005] In general, babies are hyperopic, with eye lengths shorterthan needed for optimal or near-optimal focusing of distant objectswithout accommodation. During normal development of the eye,referred to as "emmetropization," the axial length of the eye,relative to other dimensions of the eye, increases up to a lengththat provides near-optimal focusing of distant objects withoutaccommodation. In normal individuals, biological processes maintainthe near-optimal relative eye length to eye size as the eye growsto final, adult size. However, in myopic individuals, the relativeaxial length of the eye to overall eye size continues to increaseduring development, past a length that provides near-optimalfocusing of distant objects, leading to increasingly pronouncedmyopia.

[0006] The rate of incidence of myopia is increasing at alarmingrates in many regions of the world. Until recently, excessivereading during childhood was believed to be the only identifiableenvironmental or behavioral factor linked to the occurrence ofmyopia, although genetic factors were suspected. Limiting readingis the only practical technique for preventing excessive eyelengthening in children, and corrective lenses, including glassesand contact lenses, represent the primary means for amelioratingeye-length-related disorders, including myopia. The medicalcommunity and people with eye-length-related disorders continue toseek better understanding of eye-length-related disorders andmethods for preventing, ameliorating, or reversingeye-length-related disorders.

SUMMARY

[0007] Embodiments of the present invention are directed totherapeutic intervention in patients with eye-length-relateddisorders to prevent, ameliorate, or reverse the effects of theeye-length-related disorders. These embodiments of the presentinvention include methods for early recognition of patients witheye-length-related disorders, therapeutic methods for inhibitingfurther degradation of vision in patients with eye-length-relateddisorders, reversing, when possible, eye-length-related disorders,and preventing eye-length-related disorders, Additional embodimentsof the present invention are directed to particular devices used intherapeutic intervention in patients with eye-length-relateddisorders.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 provides a cross-section view of a human eye.

[0009] FIG. 2 illustrates the optical-sensing structures within theretina of the eye.

[0010] FIG. 3 illustrates the interconnection of photoreceptorneural cells through higher layers of neural circuitry.

[0011] FIG. 4 illustrates an opsin photoreceptor protein.

[0012] FIG. 5 schematically illustrates biological photoreceptionand lower levels of biological image processing,

[0013] FIG. 6 provides a top-down view of the patch ofphotoreceptor neurons shown in FIG. 5.

[0014] FIGS. 7A, 7B illustrate an example of low-level neuralprocessing of photoreceptor neural cell signals.

[0015] FIG. 8A illustrates a plot of the spatial frequency ofimages input to the retina versus axial length of the eye, whenrelatively distant scenes are observed.

[0016] FIG. 8B shows an image of a distant scene, as input to theretina, corresponding to different axial lengths of the eye.

[0017] FIGS. 9A, 9B, and 9C illustrate, using state-transitiondiagrams, control of eye lengthening in normal developing humans,lack of control of eye lengthening in myopic humans, and atherapeutic approach of certain embodiments of the presentinvention used to prevent, ameliorate, or reverse various types ofeye-length-related disorders.

[0018] FIG. 10 provides a control-flow diagram that describes ageneralized therapeutic invention that represents one embodiment ofthe present invention.

[0019] FIG. 11 illustrates an exemplary therapeutic device that isused to prevent, ameliorate, or even reverse myopia induced byexcessive reading, and/or other behavioral, environmental, orgenetic factors, and that represents one embodiment of the presentinvention.

[0020] FIG. 12 illustrates axial-length versus age curves fornormal individuals, myopic individuals, and myopic individuals towhich therapeutic interventions that represent embodiments of thepresent invention are applied.

[0021] FIGS. 13A and 13B illustrate experimental results thatconfirm the effectiveness of the therapeutic device and therapeuticintervention that are discussed with reference to FIGS. 10 and 11and that represent embodiments of the present invention.

[0022] FIGS. 14A, 14B, 14C, 14D, and 15 illustrate the source ofhypervariability that characterizes the genes that encode the I,and M opsins,

[0023] FIG. 16 illustrates the effects of genetic variation inopsin genes on the absorbance characteristics of the opsinphotoreceptor protein.

[0024] FIG. 17 illustrates the effects on average spatial frequencyof images input to the retina produced by certain types ofopsin-photoreceptor-protein variants.

[0025] FIG. 18 illustrates the predictability of the degree ofmyopia in individuals with various types of mutant opsinphotoreceptor proteins, according to one embodiment of the presentinvention.

[0026] FIGS. 19A, 19B illustrate characteristics of the filtersemployed in the therapeutic devices used to treatvariant-photoreceptor-protein-induced myopia as well as myopiainduced by other, or combinations of other, environmental,behavioral, or genetic factors, according to certain embodiments ofthe present invention,

[0027] FIGS. 20A, 20B, 20C, 20D, 20E, 20F, 20G, 20H, and 20Iillustrate, using exemplary f(x) and g(x) functions, theconvolution operation, f(x)*g(x), of two functions f(x) andg(x).

DETAILED DESCRIPTION

[0028] FIG. 1 provides a cross-section view of a human eye. The eye102 is roughly spherical in shape, and is encased by a tough, whiteouter layer 104, referred to as the "sclera," and a transparentcornea 106 through which light from external light sources passesto enter the pupil 108. Light passing through the pupil is focusedby the lens 110 onto the semi-spherical retina 112 that forms alarge portion of the internal surface of the solution-filled 114sphere of the eye. The retina includes photoreceptor neuronshierarchically interconnected through higher-level neuronalstructures that ultimately connect to photoreceptor neurons theoptical nerve 116, through which optical data collected by theretina and processed by the higher-level neuronal structures arepassed to the central nervous system. The iris 118 operates as ashutter to vary the diameter of the pupil, and thus vary the lightflux entering the pupil. The process of accommodation, in which theshape of the eye lens is changed to focus objects at variousdistances onto the retina, involves nervous excitation of theciliary muscles 120.

[0029] FIG. 2 illustrates the optical-sensing structures within theretina of the eye. In FIG. 2, a small portion 202 of the retina isshown, in cross-section, at higher magnification 204. Photoreceptorneurons, such as photoreceptor neuron 206, form a relatively denseouter layer of the retina along the cells of an inner layer of theeye 208. The photoreceptor neural cells, such as photoreceptorneuron 206, interface, through neural synapses, to bipolar cells,such as bipolar cell 210, which in turn interface to horizontalneural cells 212 and higher layers of neural cells that eventuallyinterconnect the photoreceptor neurons with the optic nerve 214.The photoreceptor neurons are the photon-sensing elements of theretina, transducing impinging photons into neural signalscommunicated to the bipolar cells 210 via synapses, such as synapse216.

[0030] FIG. 3 illustrates the interconnection of photoreceptorneural cells through higher layers of neural circuitry. In FIG. 3,a dense forest of photoreceptor neurons, including as photoreceptorneuron 302, forms a portion of the outer retina layer of the eye.The photoreceptor neurons are interconnected through bipolar,horizontal, and higher-level neural cells, represented, in theaggregate, by the neural interconnection layer 304. Thehigher-level interconnection level 304 provides initial layers ofneural processing of raw photoreceptor signals. Each different typeof photoreceptor neuron contains a corresponding type ofphotoreceptor protein, including rhodopsin for rod photoreceptorneurons and one of three different types of opsin photoreceptorproteins in the case of three different, corresponding types ofcone photoreceptor neurons. Photoreceptor proteins conformationallyrespond to a conformation change of a retinal co-factor pigmentmolecule, from a cis to trans conformation, that results fromabsorption, by the co-factor, of a photon of light having an energywithin an energy range to which the opsin photoreceptor protein isresponsive, Conformation change of the photoreceptor protein altersinteraction of the photoreceptor protein with an adjacenttransducer protein, activating the transducer to, in turn, activatea cyclic-guanosine-monophosphate ("cGMP") specificphosphodiesterase. The cGMP-specific phosphodiesterase hydrolyzescGMP, reducing the intracellular concentration of cGMP which, inturn, causes gated ion channels in the photoreceptor-neuronmembrane to close. Closing of the gated ion channels results inhyperpolarization of the photoreceptor-neuron membrane, which, inturn, alters the rate of release of the neurotransmitter glutamateinto the synapse connecting the photoreceptor neuron with higherlayers of retinal neural circuitry. In essence, at somethreshold-level change in glutamate release, the bipolar cell emitsa electrochemical signal into the higher levels of retinal neuralcircuitry. However, the retinal neural circuitry does not simplyaggregate individual photoreceptor-neural-cell-initiated signals,but instead carries out initial levels of neural processing,including feedback inhibition of photoreceptor-neural cells basedon the spatial and temporal states of neighboring photoreceptorneurons and many lower-level image-processing tasks analogous tothe lower-level image-processing tasks carried out by variouscomputational image-processing systems, including edge detection,feature detection, contrast modulation, and other such tasks.

[0031] FIG. 4 illustrates an opsin photoreceptor protein. Opsinsare members of the transmembrane protein family, in particular, themembrane-bound G protein-coupled receptors. In FIG. 4, the opsinphotoreceptor protein is illustrated as a string of beads 402, eachbead representing an amino-acid monomer. The cylindrical featuresin the illustration, such as cylindrical feature 404, representtransmembrane alpha helical segments that span thephotoreceptor-neuron membrane. As mentioned above, there are threedifferent types of opsins, referred to below as S opsin, M opsin,and L opsin. The M and L opsins are homologous, having 98-percentamino-acid-sequence identity. In primordial L and M opsins, theamino-acid monomers at 11 positions within the amino acid sequenceof the opsins, labeled in FIG. 4 by sequence number, are different.As discussed in greater detail, below, the genes encoding the M andL opsins are hypervariable. As a result, there are many differentvariants, in modern humans, of both the L and M opsin photoreceptorproteins, with much of the variation involving the 11 amino acidslabeled by sequence number in FIG. 4.

[0032] FIG. 5 schematically illustrates certain aspects of thebiology of biological photoreception and lower levels of biologicalimage processing. In FIG. 5, a small patch, or rectangular area 502of the photoreceptors at the outer portion of a human retina isshown schematically. The retina, of course, contains huge numbersof photoreceptor neurons. The photoreceptor neurons, such asphotoreceptor neuron 504, are shown as ellipsoids, with the outmostend of the ellipsoids shading-coded to indicate the type ofphotoreceptor neuron. Only cone photoreceptor neurons are shown inFIG. 5. The retina also includes a large number of rodphotoreceptor neurons. The photoreceptor neurons are connected, atthe opposite end, to the higher-level neural circuitry 506,represented as a rectangular substrate, or array, from which afinal optical signal 508 emerges. The structure schematically shownin FIG. 5 bears similarity to many electronic optical-receptordevices. In FIG. 5, three graphs 510-512 show the absorbancespectra for the three different types of photoreceptor neurons. Ineach graph, the vertical axis, such as vertical axis 516 in graph510, represents normalized absorbance values. The absorbance atwavelength .lamda., a formally unitless quantity, is defined as

A .lamda. = - ln .times. .times. ( 1 I 0 ) , ##EQU00001##

where I is the intensity of light of wavelength .lamda. that haspassed through a sample, and I0 is the intensity of the incidentlight of wavelength .lamda.. The horizontal axes, such ashorizontal axis 518 in graph 510, represent the wavelength of theincident light. Graph 510 shows the absorbance spectrum for the Sopsin, which features a maximum absorbance 520 for light ofwavelength .lamda.=420 mm. The S of "S opsin" stands forshort-wavelength. Note that the shading-coding 524 for Sphotoreceptor neurons, which contain S opsin, is shown to the rightof the graph. Graph 511 shows the absorbance spectrum for the M, ormedium-wavelength, photoreceptor neuron, and graph 512 shows theabsorbance spectrum for the L, or long-wavelength, photoreceptorneuron. The different types of opsin molecules in each of the threedifferent types of photoreceptor neurons determine the differentabsorption characteristics of the three different types ofphotoreceptor neurons. The difference absorption characteristics ofthe three different types of photoreceptor neurons provides thethree dimensions of human color vision.

[0033] FIG. 6 provides a top-down view of the patch ofphotoreceptor neurons shown in FIG. 5. Viewed top-down, thephotoreceptor neurons appear as shading-coded disks. The shadingcoding is the same shading coding used in FIG. 5. As shown in FIG.6, the L and M photoreceptor neurons together comprise roughly 95percent of the total number of photoreceptor neurons. Asillustrated in FIG. 6, the distribution of the different types ofphotoreceptor neurons appears somewhat disordered, but is notrandom.

[0034] FIGS. 7A-7B illustrate an example of low-level neuralprocessing of photoreceptor neuron signals. For purposes ofillustrating this example of low-level neural processing, the typesof the photoreceptor neurons are irrelevant, and not shown in FIGS.7A-7B by shading coding. FIGS. 7A-B show the same patch or area ofphotoreceptor neurons that is shown in FIG. 6. In FIG. 7A, a sharpillumination edge falls across the patch of photoreceptor neurons.The more highly illuminated photoreceptor neurons 702 are shownwithout shading, and the less-illuminated photoreceptor neurons areshaded 704. Line 706 represents the boundary between more highlyilluminated and less illuminated photoreceptor neurons. Suchboundaries, or edges, frequently occur in images, such as theoutline of a building against the sky or edge of a printedcharacter on a white page. In FIG. 7B, the signal responses of thephotoreceptor neurons is indicated by shading, with the cellsemitting highest-level responses shaded darkly and photoreceptorneurons emitting lowest-level responses unshaded. As can be seen inFIG. 7, the photoreceptor neurons that respond most actively to theinput illumination lie adjacent to the dark-light boundary 706. Thelower-illuminated photoreceptor neurons distant from the boundaryexhibit low signal response, such as lower-illuminatedphotoreceptor neuron 708, while the illuminated photoreceptorneurons distant from the dark-light boundary, such as photoreceptorneuron 710, exhibit only slightly higher signal response than thelower-illuminated photoreceptor neurons distant from the dark-lightboundary, but substantially lower signal response than the cellslying along the dark-light edge. This type of signal response isachieved, in the layers of neural circuitry (506 in FIG. 5), vianegative feedback of photoreceptor neurons by similarly responding,or similarly illuminated, neighboring photoreceptor neurons. Bycontrast, photoreceptor neurons with neighboring photoreceptorneurons showing significantly different signal responses, such asthe photoreceptor neurons near the dark-light edge (706 in FIG.7B), receive positive feedback, boosting their signal response.This is similar to computational edge detection, in which aLaplacian operator or other differential operator is convolved withpixels of an image in order to heighten pixel values for pixelsnear or along edges and lower the pixel values for pixels withinregions of relatively constant pixel value, or low contrast.Clearly, the aggregate signal response from the photoreceptorneurons in an area of photoreceptor neurons within the retina isproportional to the spatial frequency, or granularity of contrast,of an image focused onto the area of the retina by the lens of theeye. In general, a focused image of a distant scene input to theretina produces significantly higher spatial frequency, oredginess, than input of a blurry, or out-of-focus image. Thus, thehigher-level neural circuitry within the retina of the eye candirectly detect and respond to spatial frequency, or edginess, ofan image input to the retina and can therefore indirectly detectand respond to the degree to which images are focused.

[0035] The present inventors, through significant research efforts,have elucidated the mechanism by which the axial length of the eyeis controlled during development. FIG. 8A illustrates a plot of thespatial frequency of images input to the retina versus axial lengthof the eye, when relatively distant scenes are observed. FIG. 8Bshows an image of a distant scene, as input to the retina,corresponding to different axial lengths of the eye. As shown inFIG. 8A, the curve of the spatial frequency versus axial lengthexhibits an inflection point at between 22 and 24 mm 804, with thespatial frequency rapidly decreasing between eye axial lengths of21 mm and 24 mm. As shown in FIG. 8B, a bamboo plant appearssharply focused on the retina 810 at an axial length of 16 mm 812but becomes noticeably blurry 814 at an axial length of 24.5 mm816. As discussed above, the blurriness of the image can bedirectly detected and responded to by the lower layers of neuralcircuitry within the retina. It turns out that the axial length ofthe eye is controlled, during development, by a positiveeye-lengthening signal, a negative feedback signal, or both apositive eye-lengthening signal and a negative feedback signalproduced by the neural circuitry within the retina. A positiveeye-lengthening signal is turned off in response to the averagespatial frequency of images input to the retina decreasing below athreshold spatial frequency, while a negative feedback signal isturned on in response to the average spatial frequency of imagesinput to the retina decreasing below a threshold spatial frequency.As mentioned above, babies are generally hyperopic. In thehyperopic state, a positive eye-lengthening signal may be producedby the retinal neural circuitry to lengthen the eye towards theproper length for focusing distant objects. As the eye lengthenspast a point at which distant object lose focus, and thresholdspatial frequency decreases below the threshold value, around 24.5mm for developing eyes in preadolescent children, the positiveeye-lengthening signal is turned off, so that the eye does notfurther lengthen and further blur distant images. Alternatively,the shutdown of eye lengthening may occur as a result of a negativefeedback signal that is initiated by decrease in average spatialfrequency of images, input to the retina, past a threshold spatialfrequency.

[0036] FIGS. 9A, 9B, 9C illustrate, using state-transitiondiagrams, control of eye lengthening in normal developing humans,lack of control of eye lengthening in myopic humans, and atherapeutic approach of certain embodiments of the presentinvention used to prevent, ameliorate, or reverse various types ofeye-length-related disorders. Of course, in biological systems, theassignment of conceptual states to biological states is arbitrary,and used to emphasize certain aspects of the biological state. Forexample, there may be many ways to assign a wide variety ofdifferent states to any particular biological system. The statetransition diagrams are used to illustrate the dynamics of certainaspects of systems, rather than provide a full, detaileddescription of the systems. Note that, in FIGS. 9A, 9B, 9C, apositive eye-lengthening signal is assumed. Similartransition-state diagrams are readily developed for a negativefeedback signal that prevents further eye lengthening. FIG. 9Aprovides a state-transition diagram representing normal control ofeye lengthening during development. In an initial state 902, intowhich the vast majority of humans are born, the spatial frequencyof images input to the retina is generally high, and the images areeither in focus, without accommodation, or focus can be achieved byaccommodation. The eye can transition from the first state 902 to asecond state 904, in which there is, on average, less spatialfrequency in images input to the retina and the images are veryslightly out of focus. The eye transitions from state 902 to 904 asa result of an eye-lengthening signal, represented by edge 906,produced by the higher levels of neural circuitry within theretina. The eye can transition to a third state 908, as a result ofadditional eye-lengthening signals 910, in which there is, onaverage, less than a threshold amount of spatial frequency inimages input to the retina, and the input images are, for distantscenes and objects, out of focus. Once the threshold spatialfrequency has been crossed, the eye no longer receives, or respondsto, the eye-lengthening signal. This can be seen in FIG. 9A by theabsence of eye-lengthening-signal arcs emanating from state 908.The eye cannot lengthen further once the eye resides in the thirdstate 908. However, as the eye continues to develop and grow, theeye can transition from the third state 908 back to the secondstate 904. During development, the eye intermittently transitionsbetween the second state 904 and third state 908 so that the axiallength of the eye grows at a rate compatible with the overallgrowth of the eye and development-induced changes in other eyecharacteristics. Ultimately, in late adolescence or earlyadulthood, the eye no longer responds to the eye-lengtheningsignal, the eye no longer continues to grow and develop, and theeye therefore ends up stably residing in the third state 908.

[0037] As shown in the graph 920, in the lower portion of FIG. 9A,in which the rate of eye growth, plotted with respect to thevertical axis, depends on the spatial frequency, or blurriness, ofimages input to the retina, plotted with respect to the horizontalaxis, eye growth continues at a high rate 922 up until a thresholdspatial frequency 924 is reached, after which eye growth fallsrapidly, at least temporarily fixing the axial length of the eye toan axial length at which the average blurriness of images input tothe retina is slightly greater than the blurriness threshold thattriggered inhibition of the eye-lengthening signal.

[0038] FIG. 9B illustrates a state-transition diagram for myopicindividuals and individuals suffering from other eye-length-relateddisorders, using the same illustration conventions as used for FIG.9A. In this case, the first two states 930 and 932 are identical tothe first two states (902 and 904 in FIG. 9A) shown in FIG. 9A.However, a new third state 934 represents a state in which theaverage spatial frequency of images input to the retina isdecreased from the level of spatial frequency of state 932, butstill greater than the threshold spatial frequency that triggersinactivation of the eye-lengthening signal and/or activation of anegative-feedback signal to stop eye lengthening. In this thirdstate, unlike the third state (908 in FIG. 9A) of the normalstate-transition diagram, the eye remains responsive to theeye-lengthening signal 936 and continues to grow. This third statemay result from environmental factors, behavioral factors, geneticfactors, additional factors or combinations of various types offactors. Note that the final state, in which the average spatialfrequency of input images falls below a threshold spatialfrequency, and from which the eye can no longer lengthen 940, isnot connected to the other states by arcs, and is thereforeunreachable from the other states. As shown in graph 942 in thelower portion of FIG. 9B, eye growth continues, at a high rate,beyond the threshold spatial frequency that normally triggerscessation of eye lengthening.

[0039] FIG. 9C illustrates an approach to preventing excessive eyelengthening that underlies therapeutic embodiments of the presentinvention. FIG. 9C includes the same states 930, 932, 934, and 940that appear in the state-transition diagram of FIG. 9B. However,unlike in the state-transition diagram shown in FIG. 9B, thestate-transition diagram shown in FIG. 9C includes an additionaledge or arc 950 that provides a transition from the third state 934to state 940, in which the eye can no longer lengthen. Any therapyor therapeutic device that can decrease the average spatialfrequency of images input to the retina, indicated by arrow 950,forces a state transition to the final state 940 that is identicalto state 908 in FIG. 9A, in which the eye can no longer lengthen,and represents an embodiment of the present invention. Theseembodiments of the present invention may include specializedglasses, contact lenses, and other devices, drug therapies,behavior-modification regimes, and other such devices andtherapeutic techniques. In general, this transition 950 can bedescribed as a method for introducing artificial blurring of theimages input to the eye retina, so that the average spatialfrequency of the images falls below the threshold spatial-frequencyvalue that triggers inhibition of continued eye lengthening. Ofcourse, when artificial blurring is discontinued, as represented byarrow 952, the eye transitions back to state 934. As with state 908in FIG. 9A, the eye can also transition from state 940 back toeither of states 932 or 934 when the characteristics of the eyechange through development, rendering an applied artificialblurring insufficient to maintain the eye in state 940, or whenartificial blurring is no longer applied. As shown in graph 960 atthe bottom of FIG. 9C, when an eye-lengthening-related disorder canbe recognized or diagnosed, prior to transition of the eye to state934, then artificial blurring can be applied to force cessation ofeye lengthening at a point identical to, or similar to, the pointwhen, in normal development, a decrease in spatial frequency pastthe threshold spatial frequency inhibits further eye lengthening,as represented by curve 962. This represents application of atherapeutic intervention that prevents eye-lengthening-relateddisorders. However, even when the eye has grown past its properaxial length, represented by curve 964, application ofartificial-blurring-based therapies can nonetheless ameliorate theeffects of the eye-length-related disorder. As discussed further,below, this amelioration can transform, in certain cases, into areversal of the eye-length-related disorder as the eye continues todevelop during childhood.

[0040] FIG. 10 provides a control-flow diagram that describes ageneralized therapeutic invention that represents one embodiment ofthe present invention. In step 1002, information is received for apatient. In step 1004, a determination is made as to whether thepatient has an eye-length-related disorder. This determination canbe made in a variety of different ways. For example, certain visiontests may reveal nascent myopia in preadolescent or adolescentchildren. Alternatively, various instruments can be used todirectly measure the axial length of the eye, and compare themeasured axial length or the ratio of the measured axial length toother eye characteristics to a standard axial length or ratio forsimilarly aged or sized individuals. If a disorder is present, asdetermined in step 1006, then the therapeutic interventionrepresented by the while-loop of steps 1008-1012 continues untilthe eye no longer responds to an eye-lengthening signal or untilthe eye-length-related disorder is no longer present. During eachiteration of the while-loop, a determination is made, in step 1009,of the discrepancy between the current eye length and anappropriate eye length for the particular patient. Then, in step1010, a device or process is applied to the patient to induce alevel of artificial blurring commensurate with the discrepancydetermined in step 1009. The level of applied artificial blurringmay be proportional to the discrepancy determined in step 1009,inversely related to the discrepancy determined in step 1009, orconstant over a range of discrepancies, depending on the currentstage of the eye-length-related disorder, on the type ofeye-length-related disorder, and on other factors. After a periodof time, represented by step 1011, when eye lengthening is still apotential problem, control returns to step 1009 to again evaluatethe patient for additional application of artificial blurring.

[0041] As mentioned above, excessive reading by children is onecause of myopia. The human eye evolved for observing relativelydistant scenes and objects, rather than for focusing on detailed,close-by objects, such as printed text. Continuous close focusingon printed text results in relatively high spatial frequency imagesinput to the retina, overriding the blurriness introduced indistant scenes and objects due to eye lengthening. FIG. 11illustrates an exemplary therapeutic device that is used toprevent, ameliorate, or even reverse myopia induced by excessivereading, and/or other behavioral, environmental, or geneticfactors, and that represents one embodiment of the presentinvention. This device comprises a pair of glasses 1102 into thelenses of which small bumps or depressions, translucent inclusionsor transparent inclusions with a refractive index different fromthat of the lens material, or other such features, represented inFIG. 11 by small black dots across the lenses of the glasses, areintroduced in order to blur images observed by a patient wearingthe glasses. One lens includes a clear area 1104 to allow sharpfocus, so that the glasses wearer can continue to read andundertake other normal activities. A complementary pair of glasses1106 features a clear area 1108 in the opposite lens. Byalternating wearing of each of the pair of glasses, artificialblurring is introduced to force the average spatial frequency ofimages input to the retina of the glasses wearer below thespatial-frequency threshold, at which further eye lengthening is atleast temporarily prevented. In FIG. 11, each of the two pairs ofglasses is indicated as being worn on alternate weeks, but in otherembodiments of the present invention, the periods during which eachof the two pairs of glasses are worn may differ from a period ofone week, as indicated in FIG. 11, and may differ from one another,as well. In FIG. 11, the plots of dots-per-square-millimeter vs.distance from an edge of the lens, 1110 and 1111, illustrate theradial distribution of dot density from the center of the lenses.Decreasing dot density in the central region of the lensesfacilitates relatively normal image acquisition for portions ofscenes axially aligned with the axis of the eye, which aregenerally the portions of scenes that an observer is concentratinghis vision on, while increasingly blurring the portions of scenesthat are not aliened with the optical axis. The amount ofartificial blurring produced by the therapeutic device can becontrolled, by varying dot densities, dot dimensions, the materialof inclusions, or by varying additional or multiple characteristicsof the therapeutic device, to reduce visual acuity from 20/20 toacuity in the range of about 25/20, in certain embodiments of thepresent invention.

[0042] In another embodiment of the present invention, artificialblurring is produced by light scattering induced by incorporationof particles smaller than the wavelength of the light transmittedthrough the lenses or produced by a film or coating applied to thesurface of the lens. The amount of scatter produced by differentregions of the lens can be varied to closely mimic the blurproduced in a typical scene viewed through a near-accommodatedemmetropic eye.

[0043] In yet another embodiment of the present invention,diffraction is used to provide the blurring, Opaque or semi-opaquelight absorbing particles as large or larger than the wavelength oflight transmitted through the therapeutic-device lenses areincorporated into the lenses, applied to the surface of the lenses,or added as a film or coating. In yet another embodiment of thepresent invention, diffusers can be used to impart blurring to thelens.

[0044] In alternative embodiments of the present invention, varioustypes of progressive lenses are employed to introduce artificialblurring. Currently-available progressive lenses work to providethe most strongly negative correction in the upper part of the lensand provide a less negative correction at the bottom of the lens.These corrections facilitate focusing the visual field both fordistant and up-close objects. An inverse progressive lens thatprovides a least negative correction at the top and a most negativecorrection at the bottom would provide an artificial blur over theentire visual field, and would thus constitute an additionalembodiment of the present invention. Glasses or contact lenses thatintroduce blur by including higher-order aberration, includingglasses or contact lenses that produce peripheral aberrations,leaving the center of vision in focus, represent still additionalembodiments of the present invention.

[0045] FIG. 12 illustrates axial-length versus age curves fornormal individuals, myopic individuals, and myopic individuals towhich therapeutic interventions that represent embodiments of thepresent invention are applied. A normal individual, represented bycurve 1202, shows a constant lengthening of the eye up to lateadolescence or early adulthood, at which point eye length remainsfixed at a length of generally between 24 and 25 mm. The constantrate is controlled, as discussed above, by frequent transitions ofthe eye between states 932 and 934 in FIG. 9B. By contrast, inmyopic individuals, represented in FIG. 12 by curve 1204, eyegrowth occurs at a much greater rate, represented by the greaterslope of the linear portion of curve 1204 with respect to the curvefor normal individuals 1202. As discussed above, this greater rateof eye lengthening corresponds to the eye remaining in state 934,in FIG. 9B, in which the eye remains responsive to aneye-lengthening signal, or unresponsive to a negative-feedbacksignal, due to excessive reading or other environmental or geneticfactors. As shown by curve 1206, application of artificial blurringat five years of age increases the rate of eye lengthening and caneventually force eye length to a length slightly above, or at, theeye length of normal individuals. Curve 1206 thus represents a casein which the effects of an eye-length-relating disorder arereversed by therapeutic intervention.

[0046] FIGS. 13A and 13B illustrate experimental results thatconfirm the effectiveness of the therapeutic device and therapeuticintervention that are discussed with reference to FIGS. 10 and 11and that represent embodiments of the present invention. These datawere obtained for 20 eyes from children, all between the ages of 11and 16, who have progressing myopia and all of whom have opsinmutations that contribute to the progression of myopia. The resultsshow that therapeutic intervention brings the axial length growthrate into the normal range, preventing myopia. As shown in thegraph 1302, the rate of eye lengthening, represented by curve 1304,decreases significantly in individuals employing the therapeuticdevice illustrated in FIG. 11 in contrast to individuals wearingnormal, control lenses, represented by curve 1306. Graph 1310 showsthe growth rate of axial length, in micrometers per day, forindividuals wearing the therapeutic device shown in FIG. 11 1310versus the growth rate for individuals wearing the control lens1312.

[0047] FIGS. 14A through 14D and 15 illustrate the source ofhypervariability that characterizes the genes that encode the I,and M opsins. As shown schematically in FIG. 14A, the genes thatencode the L and M opsins are located near one another, towards theend of the X chromosome 1402. In FIG. 14A, and in FIGS. 14B, 14C,14D below, the two anti-parallel strands of DNA that togetherrepresent the X chromosome are shown one above the other, witharrows 1404 and 1406 indicating the polarity of each DNA strand,FIG. 14B illustrates the process of meiosis, in which a cellundergoes two divisions to produce four haploid gamete cells. Theprocess is shown only with respect to the terminal portion of the Xchromosome. The illustrated process occurs only in females, withrespect to the X chromosome. In females, each of the two differentX chromosomes 1410 and 1412 are replicated to produce a second copyof each chromosome 1414 and 1416, respectively. During the firstcell division, the two copies of the two X chromosomes are alignedwith respect to a plane 1420. In a first cell division, each of twodaughter cells 1430 and 1432 receives one copy of each Xchromosome, as indicated by arrows 1434-1437. The two daughtercells again divide to produce four germ cells 1440-1443, each ofwhich receives only a single X chromosome. As shown in FIG. 14C, aninternal recombination process allows portions of the sequence ofone X chromosome to be exchanged with portions of the sequence ofthe other X chromosome. This process can occur between either pairof chromosomes aligned with respect to the plane 1420. Essentially,a double-strand break occurs at the same position within one copyof the first X chromosome 1446 and one copy of the second Xchromosome 1448, and, as shown in FIG. 14C, the right-hand portionsof the two broken chromosomes are exchanged and the double-strandedbreak is repaired to produce resulting genes that include portionsof both original genes in the first and second X chromosomes. Suchcrossover events may occur repeatedly within a single gene,allowing the genetic information within genes to be shuffled, orrecombined, during meiosis.

[0048] Unfortunately, because the L and M genes are nearlyidentical in sequence, the alignment, or registering, of each pairof chromosomes across the plane, during meiosis, may be shifted, sothat, as shown in FIG. 14D, the L gene 1460 of one chromosome endsup aligned with the M gene 1462 of the other chromosome. Crossoverevents can then lead to incorporation of one or more portions ofthe L gene 1464 within the M gene 1466, and an additional,redundant M gene 1468 in one product of the crossover event andportions of the M gene 1470 in the L gene 1472, along with completedeletion of the M gene, in another product 1474 of the crossoverevent. As illustrated in FIG. 15, where a double-strandedchromosome is represented by a single entity 1480, repeatedmisaligned recombination events can lead to a large variety ofdifferent, chimeric L-gene and M-gene variants, each of whichincludes multiple regions once exclusively located in either the Lor M gene. In females, with two X chromosomes, the effects ofL-gene and M-gene hypervariability are ameliorated by X-chromosomeredundancy. However, in males, with only a single X chromosome, theeffects of L and M gene hypervariability are profound. Fully 12percent of human males are colorblind.

[0049] FIG. 16 illustrates the effects of genetic variation inopsin genes on the absorbance characteristics of the opsinphotoreceptor protein. Graph 1602 shows an absorption curve for anormal, primordial opsin photoreceptor protein. Graph 1604 showsthe absorption curve for a variant opsin photoreceptor protein.Mutations or variations in the amino-acid sequence of an opsinphotoreceptor protein can affect the absorbance curve in variousdifferent ways. For example, the wavelength of maximum absorbancemay be shifted 1606 and the term of the curve 1608 may be alteredwith respect to the normal curve. In many cases, the level ofmaximum absorbance may be significantly decreased 1610 with respectto the normal level of maximum absorbance. As discussed further,below, applying filters to light prior to entry into the eye can beused to adjust the effective absorbance spectrum of variant opsinphotoreceptor proteins with respect to normal or different variantopsin photoreceptor proteins in order to restore the relativedisplacements and magnitudes of maximum absorption observed innormal opsin photoreceptor proteins.

[0050] FIG. 17 illustrates the effects on average spatial frequencyof images input to the retina produced by certain types ofopsin-photoreceptor-protein variants. As shown in FIG. 5, in graphs511 and 512, the absorbance characteristics of the M and L opsinphotoreceptor proteins are similar, with the exception that thewavelength of maximum absorption differs by 30 nanometers betweenthe two types of opsin photoreceptor proteins. However, in the caseof a mutation to either M or L genes that produces a mutant opsinphotoreceptor protein with significantly less maximum absorbance, adiffuse image that produces low spatial frequency when input to aretina containing normal L and M photoreceptors produces, in aretina containing, for example, a normal L and low-absorbingvariant M opsin photoreceptor proteins, relatively high spatialfrequency. FIG. 17 uses the same illustration conventions as usedin FIG. 6. However, unlike in FIG. 6, where the M and Lphotoreceptor neurons have similar maximum absorption at theirrespective wavelengths of maximum absorption, in the case of FIG.17, the M photoreceptor protein is a variant that exhibits asignificantly smaller maximum absorption at the wavelength ofmaximum absorbance. In this case, a diffuse incident light, inwhich red and green wavelengths occur with relatively similarintensities and which would produce low spatial frequency on anormal retina, instead produces relatively high spatial frequencydue to disparity in maximum absorbance of the variant Mphotoreceptor proteins and normal L photoreceptor proteins. In FIG.17, edges, such as edge 1702, have been drawn between the M and Lphotoreceptor neurons. Whereas, in the normal retina, shown in FIG.6, no edges would be produced by the diffuse light. In the retinacontaining mutant M photoreceptor protein, edges occur throughoutthe retina, between adjacent L and M photoreceptor neurons. Thus,the perceived spatial frequency by the retina containing variant,low-absorbing M photoreceptor neurons is much higher than would beperceived in a normal retina by a diffuse or blurred image.Therefore, in many individuals with low-absorbing variantphotoreceptor proteins, the decrease in spatial frequency past thespatial frequency threshold that results in inhibiting further eyegrowth, in normal individuals, as discussed above with reference toFIG. 9A, does not occur, and instead the eye remains in state 934,shown in FIG. 9B, in which the eye continues to respond to aneye-lengthening signal despite the fact that axial length of theeye has exceeded the axial length for proper development andfocus.

[0051] FIG. 18 illustrates the predictability of the degree ofmyopia in individuals with various types of mutant opsinphotoreceptor proteins, according to one embodiment of the presentinvention. An observed degree of myopia, plotted with respect tothe horizontal axis 1802, is shown to be strongly correlated withdegrees of myopia predicted for the various photoreceptor-proteinmutations, or haplotypes, plotted with respect to the vertical axis1804. Predictions can be made on the detailed structure ofphotoreceptor proteins provided by x-ray crystallography,molecular-dynamics simulations, and results from application ofadditional computational and physical techniques that provide aquantitative, molecular basis for understanding the effects, onlight absorption, by changes in the sequence and conformation ofphotoreceptor proteins. Sequencing the L and M opsin genes for apatient can therefore reveal variant-photoreceptor-induced myopiaor nascent variant-photoreceptor-induced myopia, and can furtherreveal the degree of myopia expected for thevariant-photoreceptor-induced myopia, which can, in turn, informthe degree of artificial blurring that needs to be applied to thepatient at each point during application of artificialblurring.

[0052] In individuals with eye-length-related disorders arisingfrom variant photoreceptor-protein genes, the use of glasses, orcontact lenses, that incorporate wavelength filters can restore therelative absorption characteristics of the different types ofphotoreceptor proteins, and thus remove thevariant-photoreceptor-protein-induced increase in spatial frequencyand thus force a transition from uninhibited eye lengthening,represented by state 934 in FIG. 9C, to state 940, in which the eyeresponds to a lack of positive eye-lengthening signal or a negativefeedback signal. FIGS. 19A, 19B illustrate characteristics of thefilters employed in the therapeutic devices used to treatvariant-photoreceptor-protein-induced myopia as well as myopiainduced by other, or combinations of other, environmental,behavioral, or genetic factors, according to certain embodiments ofthe present invention. As shown in FIG. 19A, in the case that the Mphotoreceptor protein variant absorbs light less efficiently than anormal M photoreceptor protein, a filter that preferentiallytransmits wavelengths in region 1904 will tend to boostM-photoreceptor-protein absorption greater thanL-photoreceptor-gene absorption, and thus restore the balancebetween photoreception by the normal L photoreceptor protein andphotoreception by the variant M photoreceptor protein. By contrast,as shown in FIG. 19B, when the L photoreceptor gene is defective,and absorbs less than normal L photoreceptor protein, filters thatpreferentially pass light in the wavelength range 1906 will boostabsorption by the variant L photoreceptor protein more thanabsorption by the M photoreceptor protein, thus restoring thebalance of absorption between the two different types ofphotoreceptor proteins.

[0053] FIGS. 20A through 20I illustrate, using exemplary f(x) andg(x) functions, the convolution operation, f(x)*g(x), of twofunctions f(x) and g(x). The convolution operation is definedas:

f .function. ( x ) * g .function. ( x ) = .intg. - .infin. .infin..times. f .function. ( .alpha. ) .times. g .function. ( x - .alpha.) .times. d .times. .times. .alpha. ##EQU00002##

where .alpha. is a dummy variable of integration.

[0054] FIGS. 20A and 20B show two step functions f(.alpha.) andg(.alpha.). The function f(.alpha.) has a value of I for values ofa between 0 and 1 and has a value of 0 outside that range.Similarly, the function g(.alpha.) has a value of 1/2 for values ofa between 0 and 1 and has a value of 0 outside that range. FIG. 20Cshows the function g(-.alpha.), which is the mirror image of thefunction g(.alpha.) through the vertical axis. FIG. 20D shows thefunction g(x-.alpha.) for a particular x 2002 plotted with respectto the .alpha. axis. FIGS. 20F-H illustrate the productf(.alpha.)g(x-.alpha.) for a number of different values of x.Finally. FIG. 20I illustrates the convolution of functions f(x) andg(x) according to the above expression. The function f(x)*g(x) hasa value, at each value of x, equal to the area of overlap betweenthe f(.alpha.) and g(x-.alpha.) functions, as shown by the shadedareas 2006-2008 in FIGS. 20F-H. In other words, convolution can bethought of as generating the mirror image of the function g(x) andtranslating it from -.infin. to .infin. along the .alpha. axis withrespect to the f(.alpha.) function, at each point computing thevalue of the convolution as the area of overlap between f(.alpha.)and g(x-.alpha.). The area under the f(x)*g(x) curve, for a givenfunction g(x) is maximized when the function f(x) is equal to, orcontains, the function g(x). Thus, the integral of the convolutionof two functions from -.infin. to .infin. provides a measure of theoverlap between the two functions:

overlap .times. .times. of .times. .times. f .function. ( x ).times. .times. and .times. .times. g .function. ( x ) .times..times. is .times. .times. related .times. .times. to .times..times. .intg. - .infin. .infin. .times. f .function. ( x ) * g.function. ( x ) ##EQU00003##

Thus, using either the above integral or summation over discreteintervals, convolution of the absorbance spectrum of a filter andthe absorbance spectrum of a photoreceptor protein provides ameasure of the overlap of the absorbance filter and photoreceptorprotein. Thus, an M-boosting metric can be computed from a givenfilter, with absorbance spectrum TO, by the ratio:

M = .intg. .lamda. = - .infin. .infin. .times. T .function. (.lamda. ) * A M .function. ( .lamda. ) .intg. .lamda. = - .infin..infin. .times. T .function. ( .lamda. ) * A L .function. ( .lamda.) ##EQU00004##

where A.sub.M(.lamda.) and A.sub.L(.lamda.) are the absorbancespectra of M opsin and L opsin, respectively.

[0055] Thus, using either the above integral or summation overdiscrete intervals, convolution of the absorbance spectrum of afilter and the absorbance spectrum of a photoreceptor proteinprovides a measure of the overlap of the absorbance filter andphotoreceptor protein. Thus, an M-boosting metric can be computedfrom a given filter, with absorbance spectrum T(.lamda.), by theratio:

M = .intg. .lamda. = - .infin. .infin. .times. T .function. (.lamda. ) * A M .function. ( .lamda. ) .intg. .lamda. = - .infin..infin. .times. T .function. ( .lamda. ) * A L .function. ( .lamda.) ##EQU00005##

where A.sub.M(.lamda.) and A.sub.L(.lamda.) are the absorbancespectra of M opsin and L opsin, respectively.

[0056] Filters with M-boosting metrics significantly greater than 1may be useful in correcting myopia in individuals withlow-absorbing M-variant photoreceptor proteins, while filters withM-boosting metrics significantly below 1 may be useful in treatingmyopia in individuals with low-absorbing variant L-photoreceptorproteins. The M-boosting metric may be computed using summationsover discrete wavelengths within the visible spectrum, rather thanby integration. In general, various closed-form or numericexpressions for the absorption spectra of the L and M opsins may beused. The convolution operation becomes a multiplication forFourier-transformed functions f(x) and g(x), F(x) and G(x),respectively. It is generally more efficient to Fourier-transformf(x) and g(x), compute the product of F(x) and G(x), and the applyan inverse Fourier transform to F(x)G(x) in order to producef(x)*g(x).

[0057] Therapeutic devices that represent embodiments of thepresent invention may include filters and well as blur-inducingcoatings, inclusions, bumps, or depressions. The filter-basedapproach may be applied to a variety of different types ofvariants, including variants that show shifting of wavelength ofmaximum absorption, decreased absorption, and complex alteration ofthe absorbance curve, in order to restore the normal balancebetween the absorption characteristics of various types of opsinphotoreceptor proteins. Many different techniques and materials canbe employed to produce lens materials with particular, complexabsorption characteristics.

[0058] Although the present invention has been described in termsof particular embodiments, it is not intended that the invention belimited to these embodiments. Modifications will be apparent tothose skilled in the art. For example, therapeutic inventions, inwhich artificial focusing, rather than artificial blurring, isemployed may correct eye-length-related disorders in which theaxial length of the eye is shorter than a normal length, and theeye has failed to grow in response to high spatial frequency.Blur-inducing glasses and contact lenses and wavelength-dependentfiltering glasses and contact lenses are but two examples of avariety of different methods for inducing artificial blurriness inorder to halt eye lengthening in myopic or myopia-disposedindividuals, methods used to identify individuals witheye-lengthening disorders or individuals disposed toeye-lengthening-related disorders may include currently availablevision-evaluation techniques used by ophthalmologists andoptometrists, instrumentation for correctly measuring the axiallength of the eye, genetic techniques for determining the preciseopsin-photoreceptor-protein variance, or amino-acid sequences, inpatients, and other techniques. It should be noted that all of thevarious therapeutic devices that can be devised, according to thepresent invention, may find useful application in each of thevarious types of eye-length-related disorders, whatever theirunderlying environmental, behavioral, or genetic causes. Wavelengthfilters incorporated into lenses, for example, may provide benefitto individuals in which myopia is induced by excessive reading, andnot only to those individuals with low-absorbingphotoreceptor-protein variants. While therapeutic devices worn byindividuals are discussed, above, any therapy that inducesartificial blurring, as also discussed above, that results in atransition of the eye from a state in which the eye isnon-responsive to a negative feedback signal or continues togenerate and/or respond to a positive eye-growth sign to a state inwhich eye lengthening is halted is a potential therapeuticembodiment of the present invention. For example, drugs, includingmuscarinic receptor agonists, which would cause the ciliary body tocontract and therefore adjust the focus of the eye to a shorterfocal length at which distance objects fail to completely focus,are candidate drug therapies for introducing artificial blurringaccording to the present invention. Most currently-availablemuscarinic receptor agonists also cause the pupil to contract,changing the depth of field. A particularly useful drug fortherapeutic application, according to embodiments of the presentinvention, would not cause the pupil to contract or dilate. Whenthe pupil remains at normal size for ambient lighting conditions,the depth of field remains sufficiently small, so that a relativelysmall amount of the visual field is well focused.

[0059] The foregoing description, for purposes of explanation, usedspecific nomenclature to provide a thorough understanding of theinvention. However, it will be apparent to one skilled in the artthat the specific details are not required in order to practice theinvention. The foregoing descriptions of specific embodiments ofthe present invention are presented for purpose of illustration anddescription. They are not intended to be exhaustive or to limit theinvention to the precise forms disclosed. Many modifications andvariations are possible in view of the above teachings. Theembodiments are shown and described in order to best explain theprinciples of the invention and its practical applications, tothereby enable others skilled in the art to best utilize theinvention and various embodiments with various

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