Methods, systems, and devices for reducing the frequency and / or magnitude of photophobia or for modulating circadian cycles

Abstract

To provide methods, systems and apparatus for reducing frequency and / or severity of photophobic responses or for modulating circadian cycles.SOLUTION: An optical filter may reduce the frequency and / or severity of photophobic responses or modulate circadian cycles by controlling light exposure of cells in a human eye in specific wavelengths, such as 480 nm and 590 nm, and a visual spectral response of the human eye. The optical filter may disrupt the isomerization of melanopsin in the human eye thereby reducing the availability of an active isoform, whereas the attenuation of light weighted across the action potential spectrum of the active isoform attenuates the phototransduction cascade leading to photophobic responses. In one embodiment, an optical filter may be configured to transmit less than a first amount of light at specific wavelengths, and to transmit more than a second amount of light weighted across the visual spectral response.SELECTED DRAWING: Figure 6

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. patent application Ser. No. 15 / 673,264, filed Aug. 9, 2017, and entitled "METHODS, SYSTEMS, AND APPARATUS FOR REDUCING THE FREQUENCY AND / OR SEVERITY OF PHOTOPHOBIC RESPONSES OR FOR MODULATING CIRCADIAN CYCLES," the disclosure of which is incorporated herein by reference in its entirety.

[0002] Photophobia, or light sensitivity, represents an adverse response to light that characterizes several neurological conditions. The present invention relates to controlling the effects of light on a subject. More particularly, the present invention relates to methods, systems, and devices for reducing the frequency and / or severity of, or modulating the circadian cycle of, photophobia. [Background technology]

[0003]

[0003] The retina of the eye contains various photoreceptor cells, including rods (responsible for black and white and low light vision), cones (responsible for daytime and color vision), and melanopsin ganglion cells.

[0004] Melanopsin ganglion cells are photosensitive. This photosensitivity can transmit pain through pain pathways in the brain. These pathways are described in detail in Noseda et al., "A Neural Mechanism for Exacerbation of Headache by Light," Nat Neurosci. 2010 Feb;13(2):239-45 PMID20062053, which is incorporated herein by reference in its entirety. It has previously been demonstrated that modulating environmental light through eyeglass tinting can be effective in treating photosensitive neurological conditions, including migraine and benign idiopathic blepharospasm. An explanation for these beneficial effects can be found in Good et al., "The Use of Tinted Glasses in Childhood Migraine," Headache. 1991 Sep;31(8):533-6 PMID 1960058, and Blackburn et al., "FL-41 Tint Improves Blink Frequency Light Sensitivity and Functional Limitations in Patients with Benign Essential Blepharospasm," Ophthalmology. 2009 May;116(5):997-1001 PMID 19410958, both of which are incorporated herein by reference in their entireties. In addition to pain transmission pathways, melanopsin ganglion cells are also connected to the suprachiasmatic nucleus, where they are involved in circadian synchronization. These connections are described in detail by Hannibal J., Roles of PACAP-containing retinal ganglion cells in circadian timing, Int Rev Cytol. 2006;251:1-39. Review. PubMed PMID: 16939776, which is incorporated herein by reference in its entirety.

[0005] All animals have an endogenous "clock" that synchronizes them to Earth's 24-hour light / dark cycle. This clock establishes an internal rhythm of approximately ("circa") one day ("dian"). This phenomenon is explained by Czeisler CA, Gooley JJ., "Sleep and circadian rhythms in humans," Cold Spring Harb Symp Quant Biol. 2007;72:579-97. Review. PubMed PMID: 18419318, which is incorporated herein by reference in its entirety. However, to remain optimally synchronized with the dark / light cycle, the internal clock must be reset daily. This entrainment occurs when melanopsin ganglion cells absorb light in the surrounding environment and transmit a signal to the suprachiasmatic nucleus, the part of the brain that functions as the body's "master clock," as explained in Czeisler CA, The effect of light on the human circadian pacemaker, Ciba Found Symp. 1995;183:254-90; discussion 290-302. Review. PubMed PMID: 7656689 and Duffy JF, Wright KP Jr. Entrainment of the human circadian system by light, J Biol Rhythms. 2005 Aug;20(4):326-38. Review. PubMed PMID: 16077152, both of which are incorporated herein by reference in their entireties.

[0006]

[0006] Rhodopsin is a light-sensitive molecule in the rods and cones of the eye. It contains two metastable isomers, including an active and an inactive state. When exposed to light, rhodopsin isomerizes to an inactive isoform. The inactive isoform of rhodopsin can be restored in the retinoid cycle. During the retinoid cycle, rhodopsin leaves the photoreceptors and enters the retinal pigment epithelium. After being restored to the active isoform, rhodopsin returns to the photoreceptors. Melanopsin in melanopsin ganglion cells is thought to undergo a process similar to that described in Mure LS, Cornut PL, Rieux C, Drouyer E, Denis P, Gronfier C, Cooper HM, Melanopsin bistability: a fly's eye technology in the human retina, PLoS One. 2009 Jun 24;4(6):e5991. PubMed PMID: 19551136, which is incorporated herein by reference in its entirety. Summary of the Invention [Problem to be solved by the invention]

[0007]

[0007] Therefore, it is desirable to control the effects of light in a subject. More particularly, it is desirable to provide methods, systems, and devices that reduce the frequency and / or severity of photophobia. It is also desirable to provide methods, systems, and devices that regulate circadian cycles. [Means for solving the problem]

[0008]

[0008] Because melanopsin ganglion cells are sensitive to wavelengths of light near 480 nm and are involved in pain transmission pathways in humans, it is desirable to control the painful effects caused by certain types of light. For example, because stimulation of melanopsin ganglion cells can affect the frequency and / or severity of photophobic responses, in some situations it may be beneficial to reduce direct light stimulation of these cells, or in other situations to reduce exposure to light not directly related to stimulation of these cells. These photophobic responses include migraine headaches, photosensitivity associated with concussion or traumatic brain injury, photosensitive epilepsy, and photosensitivity associated with benign idiopathic blepharospasm. Melanopsin ganglion cells are also involved in circadian rhythms. Therefore, Thus, methods, systems, and devices are provided for reducing the frequency and / or magnitude of photophobia and / or regulating circadian cycles by controlling the exposure of melanopsin ganglion cells or other parts of the eye to light.

[0009]

[0009] In one embodiment, a device for reducing the frequency and / or magnitude of photophobia or modulating circadian rhythm is described. The device includes an optical filter configured to transmit light less than a first amount of light weighted across the absorption spectrum of a bistable isoform of melanopsin and to transmit light greater than a second amount of light weighted across the visual spectral response. Illustratively, the light spectrum associated with the absorption spectrum of the active isoform of melanopsin is at wavelengths near 480 nm, and the light spectrum associated with the absorption spectrum of the inactive isoform of melanopsin is at wavelengths near 590 nm.

[0010] In some embodiments, the first amount of light is about 50% of the light weighted across the absorption spectrum of one or both of the bistable isoforms of melanopsin, and the second amount of light is about 75% or more of the light weighted across the visual spectral response. In other embodiments, the first amount of light is about 25% of the light weighted across the absorption spectrum of one or both of the bistable isoforms of melanopsin, and the second amount of light is about 60% or more of the light weighted across the visual spectral response. In another embodiment, the first amount of light is substantially the entire light weighted across the absorption spectrum of one or both of the bistable isoforms of melanopsin. In yet another embodiment, the second amount of light is substantially the entire light weighted across a spectrum outside the absorption spectrum of one or both of the bistable isoforms of melanopsin and / or outside the absorption spectrum of one or both of the bistable isoforms of melanopsin, weighted across the visual response spectrum. In yet another embodiment, the ratio of the attenuation of the first amount of light weighted across the absorption spectrum of one or both bistable isoforms of melanopsin to the attenuation of the second amount of light weighted across the visual spectral response is greater than 1.

[0011] In some embodiments, the first amount of light is substantially all of the light within the action potential spectrum of the melanopsin ganglion cells below the wavelength of the long-pass filter, and the second amount of light is all of the light across the visual spectral response including wavelengths above the wavelength of the long-pass filter. In other embodiments, the first amount of light can be substantially all of the light above a short-pass filter wavelength near 590 nm, and the second amount of light can be substantially all of the light across the visual spectral response including wavelengths below the short-pass filter wavelength.

[0012] In some embodiments, the second amount of light comprises a third amount of light including wavelengths less than the maximum relative response of the action potential spectrum of the melanopsin ganglion cell and / or wavelengths greater than about 590 nm. In other embodiments, the second amount of light comprises a third amount of light including wavelengths greater than the maximum relative response of the absorption spectrum of one or both bistable isoforms of melanopsin. In another embodiment, the second amount of light comprises a third amount of light including wavelengths less than the maximum relative response of the absorption spectrum of one or both bistable isoforms of melanopsin, and a fourth amount of light greater than the maximum relative response of the absorption spectrum of one or both bistable isoforms of melanopsin.

[0013] In some embodiments, the first amount of light is measured as the amount of light received by a cell in the eye (i.e., across the absorption spectrum of one or both of the bistable isoforms of melanopsin) (D rec ) and the second amount of light is the amount of light received across the visual response spectrum (D vis ), and the ratio including the first light amount and the second light amount is defined as a figure of merit (FOM), which is calculated by the following formula:

number

[0014]

[0014] In the formula, D rec (T=1) is the first light amount without an optical filter, and D vis (T=1) is the second amount of light without the optical filter. In some embodiments, the figure of merit of the optical filter can include values ​​of about 1, greater than about 1, greater than about 1.3, greater than about 1.5, greater than about 1.8, greater than about 2.75, greater than about 3, and greater than about 3.3. In other embodiments, other figures of merit can be used.

[0015] In some embodiments, the first light intensity defines a spectral width centered at the median absorption spectrum of one or both bistable isoforms of melanopsin. In other embodiments, the first light intensity and the second light intensity are determined based on characteristics of ambient light. In yet another embodiment, the first light intensity and the second light intensity are selectively tunable with transition, photochromic, or electrochromic dyes, pigments, or coatings.

[0016] In some embodiments, the optical filter includes at least one layer configured to minimize or reduce the effect of the angle of incidence of received light. In another embodiment, the optical filter further includes a substrate including an impregnated or coated color.

[0017]

[0017] In one embodiment, a system for reducing the frequency and / or severity of photophobia or modulating circadian rhythm is described. The system includes a substrate, a first layer disposed on the substrate, and a second layer disposed adjacent to the first layer. The first layer includes a high refractive index material. The second layer includes a low refractive index material.

[0018] In another embodiment, the system may include additional layers and / or types of materials that cooperate to transmit less than a first amount of light weighted over the action potential spectrum of the melanopsin ganglion cells and more than a second amount of light weighted over the visual spectral response. In some embodiments, increasing the number of layers in the optical filter increases the transmittance of light outside the action potential spectrum.

[0019]

[0019] In one embodiment, a method for fabricating an optical filter that reduces the frequency and / or severity of photophobia is described. The method includes determining an appropriate light spectrum. A first amount of light received by one or both bistable isoforms of melanopsin in a subject is determined. A second amount of light related to the visual response spectrum is determined. The first amount of light and the second amount of light are used to fabricate an optical filter.

[0020] In some embodiments, the action potential spectrum of a human melanopsin ganglion cell is In another embodiment, the optical filter is configured to attenuate the first amount of light based on melanopsin activity in human ganglion cells. In a different embodiment, the optical filter is manufactured based on visual response spectral characteristics.

[0021] In some embodiments, the optical filter is a notch filter. In another embodiment, the notch filter is configured to block light irradiating at non-normal angles of incidence. In yet another embodiment, the notch filter comprises a filter optimized for multiple oblique angles of incidence. In yet another embodiment, the notch filter is designed with a slight red shift. In yet another embodiment, the notch filter comprises a filter notch that attenuates light over a spectral width.

[0022] In some embodiments, fabricating an optical filter includes using multilayer dielectrics, nanoparticle-buried coatings, color filters, tinting, resonant waveguide mode filters, rugate filters, and any combination thereof. In another embodiment, the nanoparticle-buried coating includes at least one of metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material serving as the shell. In yet another embodiment, the at least metal nanoparticles include at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles, and the dielectric nanoparticles include at least one of TiO2, Ta2O5, or other dielectric nanoparticles. In yet another embodiment, the semiconductor nanoparticles or quantum dots include at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles. In yet another embodiment, the shape of the embedded nanoparticles in the nanoparticle-buried coating is spherical, ellipsoidal, or another shape. In some embodiments, the extinction spectrum of the embedded nanoparticles is determined using Mie scattering theory.

[0023]

[0023] In one embodiment, a method for reducing the frequency and / or magnitude of photophobia or modulating circadian cycle is described. The method includes the steps of: receiving an amount of light; transmitting less than a first amount of light weighted across the absorption spectrum of one or both bistable isoforms of melanopsin; and transmitting more than a second amount of light weighted across the visual spectral response. The attenuation of the light weighted across the absorption spectrum of one or both bistable isoforms of melanopsin disrupts isomerization of one or both bistable isoforms of melanopsin.

[0024] The drawings constitute a part of this specification and include exemplary embodiments of the invention that may be embodied in various forms. It will be understood that in some instances various aspects of the invention may be shown exaggerated or enlarged to facilitate an understanding of the invention. [Brief explanation of the drawings]

[0025] [Figure 1]

[0025] FIG. 1 shows an exemplary measured action potential spectrum of a melanopsin cell normalized to unity volume and a Gaussian fit to the measured data points. [Figure 2]

[0026] FIG. 1 shows the measured transmission spectrum of an exemplary FL-41 35 filter across the effective action potential spectrum of melanopsin. [Figure 3]

[0027] FIG. 1 shows the measured transmission spectrum of an exemplary FL-41 35 filter across the visible light spectrum. [Figure 4]

[0028] FIG. 1 shows the measured transmission spectrum of an exemplary FL-41 55 filter across the effective action potential spectrum of melanopsin. [Figure 5]

[0029] FIG. 1 shows the measured transmission spectrum of an exemplary FL-41 55 filter across the visible light spectrum. [Figure 6]

[0030] FIG. 1 is a diagram of an exemplary filter using multilayer dielectric thin films with different refractive indices. [Figure 7]

[0031] FIG. 1 is a diagram of an exemplary filter using a nanoparticle embedded coating designed to scatter light in the blue-green region of the visible light spectrum. [Figure 8]

[0032] FIG. 1 illustrates an exemplary method for designing optical filters that interfere with light absorption by melanopsin cells. [Figure 9]

[0033] FIG. 1 shows the measured transmission spectrum of a filter of one embodiment across the "effective action potential spectrum" of melanopsin. [Figure 10]

[0034] FIG. 10 shows the measured transmission spectrum of the filter of the embodiment shown in FIG. 9 across the visible light spectrum. [Figure 11]

[0035] FIG. 10 shows the measured transmission spectrum of another embodiment of a filter across the "effective action potential spectrum" of melanopsin. [Figure 12]

[0036] FIG. 10 shows the measured transmission spectrum of another embodiment filter across the “effective action potential spectrum” of melanopsin. [Figure 13]

[0037] FIG. 10 shows the measured transmission spectra of different alternative embodiment filters across the "effective action potential spectrum" of melanopsin. [Figure 14]

[0038] FIG. 14 shows the measured transmission spectrum of the filter of the embodiment shown in FIG. 13 across the visible light spectrum. [Figure 15]

[0039] FIG. 10 shows the measured transmission spectrum of yet another embodiment of a filter, centered at 485 nm for normally incident light, across the "effective action potential spectrum" of melanopsin. [Figure 16]

[0040] FIG. 16 shows the measured transmission spectrum of the embodiment shown in FIG. 15 across the "effective action potential spectrum" of melanopsin at an angle of incidence of 15 degrees. [Figure 17]

[0041] FIG. 10 shows the measured transmission spectrum of yet another embodiment of a filter, excluding the low refractive index MgF 2 layer, across the “effective action potential spectrum” of melanopsin. [Figure 18]

[0042] Figure 18A shows the measured transmission spectrum of an embodiment of a filter centered at about 480 nm, and Figure 18B shows the measured transmission spectrum of an embodiment of a filter centered at about 620 nm. [Figure 19]

[0043] FIG. 1 shows measured transmission spectra of several embodiment filters centered at about 480 nm with varying degrees of coloration. [Figure 20]

[0044] FIG. 20 shows the rear reflection spectrum of the filter of the embodiment shown in FIG. 19. [Figure 21]

[0045] 1 illustrates an exemplary embodiment of a method for manufacturing an optical filter. [Figure 22]

[0046] FIG. 1 illustrates an exemplary embodiment of a method for reducing the frequency and / or magnitude of photophobia or modulating circadian cycles. [Figure 23]

[0047] FIG. 1 illustrates an embodiment of a composite filter configured to preferentially attenuate two wavelength ranges. [Figure 24]

[0048] 1A-1C illustrate an embodiment of a method for manufacturing a composite optical filter. [Figure 25]

[0049] FIG. 1 illustrates one embodiment of a method for reducing the frequency and / or magnitude of photophobia or modulating circadian cycles using a composite filter. [Figure 26]

[0050] Figure 26A shows the transmission spectrum of a gray tinted lens coating centered at 480 nm, and Figure 26B shows the transmission spectrum of a gray tinted lens coating centered at 620 nm. [Figure 27]

[0051] FIG. 1 is a schematic diagram illustrating the cyclic isomerization of a bistable dye. [Figure 28]

[0052] FIG. 1 shows the response spectra of active and inactive melanopsin in the eye. [Figure 29]

[0053] FIG. 1 shows one embodiment of a method for disrupting the isomerization of one or both bistable isoforms of melanopsin. [Figure 30]

[0054] FIG. 1 shows the relative response versus wavelength of light according to the color matching functions of the samples. [Figure 31]

[0055] FIG. 1 shows the relative response versus wavelength of light according to the color matching functions of the samples when a 480 nm filter is used. [Figure 32]

[0056] FIG. 10 shows the relative response versus wavelength of light according to the color matching functions of the samples when both a 480 nm filter and a 590 nm filter are used. DETAILED DESCRIPTION OF THE INVENTION

[0026]

[0057] Detailed descriptions of embodiments of the present invention are provided herein. However, it is understood that the present invention can be embodied in various forms. Accordingly, the specific details disclosed herein are not intended to be limiting, but rather as representative information for teaching those skilled in the art how to utilize the present invention in virtually any system, structure, or method.

[0027]

[0058] The present invention relates to controlling the effects of light on a subject. Some applications of the present invention relate to methods, systems, and devices for reducing the frequency and / or magnitude of photophobia or modulating circadian cycles.

[0028]

[0059] Different people experience photophobia in different ways. The wavelengths and associated transduction pathways that cause adverse light reactions may vary depending on the patient. However, there are some common wavelengths that are more commonly associated with photophobia than others. For example, melanopsin ganglion cells in the eye are sensitive to light with a wavelength of approximately 480 nm. In some individuals, this may be related to the individual's neurological symptoms of photosensitivity. Controlling exposure to light with a wavelength around 480 nm may be beneficial for these individuals and may reduce or prevent the individual's neurological symptoms of photosensitivity. Alternatively, or in addition, adjusting exposure to that same light may also help regulate the individual's circadian rhythm. In the same or other individuals, adjusting eye exposure to light with a wavelength around 620 nm or other wavelengths may also be beneficial for reducing or preventing the neurological symptoms of photosensitivity or for regulating the individual's circadian rhythm. Although the following examples refer to attenuation of light containing wavelengths near 480 nm and exposure of melanopsin ganglion cells to the same light near 480 nm, it will be understood that similar filters and methods can be used to attenuate light of other wavelengths received by other cells in the eye. For example, similar filters and methods can be used to attenuate light at or about 620 nm. In another example, similar filters and methods can be used to attenuate light at or about 590 nm.

[0029]

[0060] Because melanopsin ganglion cells are believed to be responsible for photophobia and the development of migraines in many photophobic patients, it is desirable to block at least a portion of the visible spectrum that activates these cells. Photophobia is associated with light-sensitive neurological conditions, including migraines, benign idiopathic blepharospasm, and traumatic brain injury (TBI). Figure 1 shows an exemplary unit-normalized measured action potential spectrum of a melanopsin cell and a Gaussian fit to the measured data points. While this Gaussian fit may be used for filter design in at least one embodiment, this Gaussian fit should not be interpreted as a spectral criterion for an optimal filter, as more accurate measurements of the action potential spectrum may become available. This accurate measurement may guide alternative filter designs or methods according to or via a similar process described herein. Optimization of the methods, systems, and devices described herein based on more accurate measurements of the action potential spectrum is contemplated.

[0030]

[0061] In some embodiments, light may be blocked (i.e., attenuated) over a specific wavelength range suitable for preventing photophobia while minimizing distortion of the visible spectrum. In other embodiments, the methods, systems, and devices described herein may also be used to manipulate the body's circadian system.

[0031]

[0062] Embodiments of optical filters are described that block specific portions of the optical spectrum suspected of triggering and / or exacerbating these photophobic reactions. These filters may be applied to eyewear (such as eyeglasses, goggles, clip-ons, or other eyewear), lenses (including contact lenses), computer screens, windows, car windshields, lighting substrates, light bulbs (incandescent, fluorescent, CFL, LED, gas vapor, etc.), or any other optical element. These optical filters may be applied to crown glass (including BK7), flint glass (including BaF8), SiO2, plastics (such as polycarbonate, CR-39, and trivex), other substrates, and combinations thereof.

[0032]

[0063] While the majority of the discussion focuses on preventing photophobia, the systems, methods, and devices described herein are also applicable to regulating circadian rhythms. For example, these filters can be used to manipulate the body's circadian system by entrepreneurs, athletes, and others who travel between different time zones or who wish to manipulate their circadian system. In one example, a subject wears at least one filter described herein to help the subject adapt to the light / dark cycle of the location to which the subject travels. In another example, at least one filter described herein can be used to limit the excitation of melanopsin ganglion cells in patients with sleep disorders. In this application, the subject wears these filters to limit their exposure to artificial light in the evening, preventing their internal clock from determining that it is time to be awake. In addition, the subject can adjust their light / dark cycle by increasing their exposure to light before sunrise.

[0033]

[0064] Furthermore, it has recently been clinically demonstrated that wavelengths around 620 nm also contribute to photophobia in certain individuals. Although the exact pathways for neurological effects are not yet fully understood, benefits may similarly be achieved by preferentially attenuating light containing wavelengths around 620 nm.

[0034]

[0065] Melanopsin includes bistable isoforms, each of which exhibits a unique absorption spectrum. The isoforms can be active isoforms and inactive isoforms. The active isoforms can be physiologically active. The inactive isoforms can be physiologically inactive. Absorption of light based on the absorption spectrum of each isoform can result in isomerization of melanopsin. Benefits can be achieved by attenuating light at or about 590 nm to hinder, limit, or prevent isomerization of melanopsin.

[0035]

[0066] FL-41 lens tints are sometimes used for migraine sufferers. FL-41 tints block (through absorption) a broad range of wavelengths. These wavelengths include those associated with melanopsin absorption. FL-41 dyes can be infused into certain types of plastic eyeglass lenses. The amount of dye infused determines the overall level of light intensity that is blocked. FL-41 35 tints are effective for many patients in indoor environments. However, if light sources increase in intensity, for example, by moving to an outdoor environment, FL-41 35 may not be as effective.

[0036]

[0067] FIG. 2 shows the measured transmission spectrum of FL-41 35. FIG. 2 further illustrates the effect of the FL-41 35 filter on the action potential spectrum of melanopsin, referred to as the "effective action potential spectrum." The FL-41 35 coloration blocks or attenuates approximately 55% of the light that would otherwise be absorbed by melanopsin ganglion cells. Furthermore, as shown in FIG. 3, the FL-41 coloration blocks a large portion of the visible spectrum not associated with melanopsin, resulting in approximately 47% attenuation across the visual response spectrum. Further blocking of the visible response spectrum can be detrimental. For example, blocking the visible response spectrum can adversely affect normal vision. In other instances, blocking the visible response spectrum can create an undesirable color scheme that may be distracting or less desirable to the wearer.

[0037]

[0068] In bright light situations, such as outdoor environments, tints with greater levels of spectral attenuation, such as "FL-41 55," may be used. The transmission spectrum of this filter and its effect on the action potential spectrum are shown in FIG. 4 (across the "effective action potential spectrum" of melanopsin) and FIG. 5 (across the visible light spectrum). This filter attenuates approximately 89% of the light that would otherwise be absorbed by melanopsin cells, but also attenuates approximately 81% of the visual response spectrum. This additional spectral attenuation may further impair vision in low light levels or other situations.

[0038]

[0069] Overall, general drawbacks of FL-41 include its rose-tinted appearance, distortion of color vision, limited applicability (i.e., it may only be applicable to certain plastics and not glass lenses, computer screens, windows, car windshields, lighting substrates, light bulbs, or other optical elements), and poor quality control over the tinting process (due in part to variations in the tintable hard coating layer). While FL-41 may be effective in certain applications, it is not designed to downregulate the stimulation of melanopsin ganglion cells and their binding to pain centers in the brain. For these reasons, it may be desirable to develop other embodiment filters.

[0039]

[0070] An example of a more desirable optical filter for treating photosensitivity may include a long-pass filter. To adjust the exposure of melanopsin ganglion cells to wavelengths of approximately 480 nm, the long-pass filter may transmit more wavelengths longer than approximately 500 nm or 520 nm, while attenuating light at wavelengths shorter than approximately 500 nm or 520 nm. Similarly, to adjust the exposure of cells in the human eye to wavelengths of approximately 620 nm, the short-pass filter may transmit more wavelengths shorter than approximately 600 nm or 580 nm, while attenuating light at wavelengths longer than approximately 600 nm or 580 nm.

[0040]

[0071] Other examples of more desirable optical filters include filters, sometimes called band-stop or minus filters, that block only the spectrum of light absorbed by melanopsin or other specific wavelengths while transmitting the rest of the light spectrum, such that the filter's spectral transmittance response takes the form of a notch. In the case of melanopsin, the center of the notch may be near the absorption maximum wavelength of the melanopsin transduction pathway (approximately 480 nm), although other locations may also be effective. The spectral width of the notch may roughly correspond to the width of the action potential spectrum, which is approximately 50-60 nm, although other widths are also possible.

[0041]

[0072] Optical filter technologies such as dye blends, multilayer dielectrics (an example is shown in FIG. 6), nanoparticle-embedded coatings (an example is shown in FIG. 7), resonant waveguide filters, or combinations thereof, can be used to form filters according to the present disclosure. Nanoparticle coatings that can be used in optical filters according to the present disclosure can include metal nanoparticles (e.g., Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g., TiO2, Ta2O5, etc.), semiconductor nanoparticles or quantum dots (e.g., Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell particles consisting of one material in the core and another material acting as the shell, other nanoparticles, or combinations thereof. The shape of these particles can be spherical, ellipsoidal, other shapes, or combinations thereof. The host material can include polymers, sol-gels, other hosts, or combinations thereof. The extinction spectra of these nanoparticles can be calculated using Mie scattering theory or its derivatives.

[0042]

[0073] One embodiment of a multi-layer filter 600 shown in FIG. 6 includes a substrate 602, a first layer 604, and a and a second layer 606. As shown, the first layer 604 can include a high refractive index material, and the second layer 606 can include a low refractive index material. In other embodiments, the first layer 604 can include a low refractive index material, and the second layer can include a high refractive index material. Furthermore, the first layer 604 is shown adjacent to the substrate 602. In other embodiments, the first layer 604 can include other layers (e.g., the second layer 606 and / or other layers) between the substrate 602 and the first layer 604. Additional layers are also shown (but not numbered). The substrate 602 can be any substrate described herein. For example, the substrate 602 can include a color layer (not shown) on the same side and / or opposite the first layer 604 and second layer 606 (i.e., the front and / or back side of the substrate). In other examples, the substrate 602 itself can be infused with color. Exemplary coloring techniques and amounts of color are described below. Other embodiment multi-layer filters are further described herein.

[0043]

[0074] The filter 700 shown in FIG. 7 includes a substrate 702, a matrix layer 704, and a plurality of nanoparticles 706. The matrix layer 704 is shown adjacent to the substrate 702. In other embodiments, the matrix layer 704 may include other layers between the substrate 702 and the matrix layer 704 (e.g., the second layer 606 shown in FIG. 6 and / or other layers). However, while the nanoparticles 706 are shown as spherical and uniformly sized, as noted above, other shapes and dimensions are also contemplated. As with the multi-layer filter of FIG. 6, various substrates, colors, other features, or combinations thereof, may be used with the nanoparticle filter 700. Other nanoparticle filter embodiments are described herein.

[0044]

[0075] Other types of filters that can be used include color filters (organic dyes and semiconductors), resonant guided-mode filters, rugate filters, or combinations thereof. Rugate filters utilize a sinusoidal refractive index variation across their thickness. A true sine function may not be available and is often approximated by a stepped refractive index approximation using a mixture of two or more materials.

[0045]

[0076] In addition to these various filter types, further considerations may include the impact of the designed filter on the visual response spectrum, which is determined by the photoreactions of rods and cones. One consideration may include minimizing spectral distortion. Considering the blue-shift in the filter response that occurs with off-axis illumination, additional or other constraints may be considered in the filter design, including optimization methods such as considering angular sensitivity, which may be compensated for, for example, by designing the notch center slightly red-shifted from approximately 480 nm when attenuating light near 480 nm toward melanopsin ganglion cells using multilayer dielectrics. Depending on the wavelength being attenuated, the degree of red-shift or blue-shift may vary. Optimization may further include broadening the filter's spectral width to compensate for non-normal angles of incidence and / or compensating for the angle of incidence through the use of additional filter layers. Potential back reflections may be a consideration. One or more of these considerations may be addressed by incorporating some form of tinted filter.

[0046]

[0077] Described herein is one embodiment of a method for fabricating an optical filter that prevents light absorption by melanopsin cells. The amount of light received by a melanopsin cell, D, can be expressed as: D melan =∫L(λ)T(λ)M(λ)dλ (1) where L is the light spectrum (in terms of intensity, power, photons / second, etc.), T is the spectral transmittance of a filter located between the light source and the eye, and M is the normalized action potential response spectrum of melanopsin, currently estimated from Figure 1 to be a Gaussian function centered at 480 nm with a full width at half maximum of 52 nm. For generality, we will assume L=1 so as not to limit the discussion to any particular light source, although the analysis can be performed for any light source with a known spectrum.

[0047]

[0078] Similar amounts of light can be calculated in relation to the visual response spectrum. D vis=∫L(λ)T(λ)V(λ)dλ (2) where V represents the normalized visual response spectrum.

[0048]

[0079] The effect of an optical filter, such as FL-41 tint, is to reduce the amount of light, as can be explained by taking the ratio of the amount of light calculated with the filter to the amount of light without the filter, for example:

number

[0049]

[0080] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0050]

[0081] A figure of merit (FOM) can also be defined that compares the masking of the melanopsin response to the masking of the visual response spectrum.

number

[0051]

[0082] FIG. 8 illustrates one embodiment of a method 800 for designing an optical filter that interferes with light absorption by melanopsin cells. The method 800 may include determining the amount of light D received by the melanopsin cells (e.g., using Equation 1), as shown in step 802. The amount of light received across the visual response spectrum may be determined (e.g., using Equation 2), as shown in step 804. A figure of merit (FOM) may be determined relating the amount of light received by the melanopsin cells and the amount of light received across the visual response spectrum, as shown in step 806. In other embodiments, the amount of light across the visual response spectrum may be reduced or separated. For example, only one or more portions of the visual response spectrum may be used, or wavelengths outside the visual response spectrum may be considered. The figure of merit may be used to design optical elements to reduce and / or prevent photophobia.

[0052]

[0083] Many embodiments described herein use multilayer dielectric thin films with different refractive indices. These layers (as described herein) can be applied to many optical elements. By way of example, and without intending to be limiting in any way, the optical filter design embodiments of the present disclosure assume a typical transparent substrate, such as an eyeglass lens, with a refractive index of approximately 1.5 and an anti-reflective coating applied to the back surface (i.e., the surface closest to the user's eye). Accordingly, other substrates with other refractive indices and with or without a back anti-reflective coating are contemplated. Minor modifications in the filter design may be necessary to compensate for different substrate materials and / or different coatings thereon. Additional considerations may need to be addressed, such as the compatibility of various thin film materials with various substrate materials and the curvature of the lens substrate, which may require further design optimization. The substrate may include an adhesion layer (e.g., a thin layer of chromium) between the substrate or a layer on the substrate and any additional coatings.

[0053]

[0084] There are numerous design approaches to multilayer longpass and notch filters that can be used. For example, software and other design tools are available for designing thin-film optical filters. These tools may consider many constraints during optimization, reducing the likelihood that any two filter designs will be identical, even if they achieve the same light-blocking characteristics or produce the same physiological results. Only a few examples appear herein, and are not intended to be limiting in any way. In addition to other approaches that can be taken to achieve similar results, further optimization can be performed in accordance with the present disclosure to provide more ideal characteristics or to provide similar characteristics with fewer layers.

[0054]

[0085] Additionally, multilayer coatings and other coatings may be applied to the tinted lens or substrate. This combination may be desirable for several reasons. One reason may include that the spectral characteristics of the tint may relax design constraints on thin-film filters. For example, combining an FL-41 "base tint" with a thin-film notch filter may serve to reduce the depth of the notch required to produce a therapeutic result. It may be desirable to account for spectral variations in the transmittance of the tint in the notch design. This design adjustment may be achieved, for example, by shifting the center wavelength of the notch to compensate for local tilts in the tint spectral response. Another reason for using a base tint may be to reduce any unwanted reflections of light entering through the back side of the lens. In this case, it may be desirable to use a "flat" or neutral tint that does not introduce any coloration of its own.

[0055]

[0086] For example, in one embodiment of a filter designed to block light in a certain wavelength range from passing in front of a lens (e.g., by reflecting desired wavelengths away from the user), light entering the back side of the lens (including light in the blocked wavelengths) can be reflected back into the user's eyes. In other words, light that is blocked from the front (by reflection, in the case of a multi-layer filter) can then be reflected from the back side. This may not be a concern when there is primarily a single light source in front of the subject. However, when a very bright light is observed, or when there are multiple light sources, for example, this back reflection can be harmful to the user.

[0056]

[0087] An exemplary approach to creating a longpass or notch filter involves using alternating layers of high and low refractive index materials. Exemplary low refractive index dielectric materials include MgF2 and SiO2. MgF2 is commonly used in single and multilayer anti-reflective coatings. Exemplary high refractive index materials include TiO2, Ti3O5 , metal oxides such as ZrO2, and Ta2O5, as well as Si3N4. Many other suitable materials may be used, including polymer layers.

[0057]

[0088] Optical filters that attenuate light around various wavelengths, such as 480 nm, 620 nm, or other specific wavelengths, can follow a similar design. One embodiment optical filter design and its effect on the spectrum of light illuminating melanopsin cells that generate effective (and attenuated) action potentials are shown in Figures 9 and 10. This design is similar to the FL-41 design in that 55% of the light absorbed by melanopsin cells is blocked or attenuated. Targeted to be as clinically effective as the FL-35 coating, this design should provide the same relief of migraine (or light sensitivity) symptoms as the FL-41 coating, with only an 18% attenuation across the visual response and significantly less visual distortion. In this embodiment, the low refractive index material is SiO2, the high refractive index material is TiO2, and MgF2 is used as the outermost layer, for a total of 11 layers. Exemplary layers and materials are listed in the following table, from the outermost layer (MgF2) to the innermost layer adjacent the substrate (165 nm thick TiO2). This filter has an FOM≈3. [Table 1]

[0058]

[0089] The spectral position of the center of the notch filter may be determined by the thickness of each layer of the notch filter. However, although many embodiments herein assume that the spectral position of the notch is approximately 480 nm, other spectral positions are contemplated. For example, as more information becomes known about the action potential spectrum of the melanopsin transduction pathway, the spectral position may be shifted to, for example, 620 nm in accordance with the new information. Alternatively, in other examples, the spectral position may be positioned to achieve a particular result, for example, to attenuate wavelengths other than those in the action potential spectrum of the melanopsin transduction pathway.

[0059]

[0090] The width of the notch can be determined by the difference in refractive index of the different layers. can be determined by the number of layers. The transmittance outside the notch region can be increased and flattened by including additional layers, and potentially including a single-layer or multi-layer anti-reflective coating added to the posterior surface of the lens to further reduce rear reflections. Further design optimization can be used to increase the depth of the notch, which can further suppress melanopsin cell excitation, but the impact on the visual response spectrum must be considered. As is useful in many cases, the overall suppression can be tailored for each patient or by designing one or more general grade filters.

[0060]

[0091] Greater attenuation of the effective melanopsin action potential spectrum can be achieved by deepening or widening the filter notches, or by a combination of both. Figures 11 and 12 show two exemplary approach embodiments using 19 and 15 dielectric layers, respectively. Both provide approximately 70% attenuation across the melanopsin spectrum, but have slightly different visual response spectrum characteristics, so the final choice between the two can be made based on the wearer's preference. The 19-layer filter attenuates approximately 21% of the visual response spectrum, while the 15-layer filter attenuates approximately 25% of the visual response spectrum. Both filters have FOM values ​​greater than 2.75, with the 19-layer filter having an FOM value of approximately 3.3.

[0061]

[0092] Various designs can achieve significant attenuation across the melanopsin action potential spectrum. Figures 13 and 14 show one embodiment notch filter design that has an FOM value of approximately 3 and uses 19 dielectric layers to provide attenuation of melanopsin action potentials similar to the FL-41 55 filter, which blocks approximately 89% of light but only approximately 29% of the visual response spectrum. Exemplary layers and materials are listed in the following table, from the outermost layer (MgF2) to the innermost layer adjacent the substrate (160.3 nm thick TiO2). [Table 2]

[0062]

[0093] Other design considerations may include blocking light that strikes at non-normal angles of incidence. For example, tilting the angle of a thin film filter tends to result in a blue shift in the filter response. This can be accommodated by either intentionally designing the filter with a slight red shift, adding additional layers to increase the width of the filter, or a combination thereof, to minimize or reduce the effect of the angle of incidence.

[0063]

[0094] Figure 15 shows a 10-layer filter design in one embodiment with a notch centered at 485 nm for normally incident light. At normal incidence, this filter blocks approximately 61% of the light in the melanopsin spectrum and attenuates only approximately 21% of the light in the visual response spectrum, resulting in an FOM value of approximately 2.9.

[0064]

[0095] FIG. 16 shows the effect of the filter of the embodiment shown in FIG. 15, but at an angle of incidence of about 15 degrees. In this embodiment, at this angle of incidence, the blocking of the amount of light to melanopsin is about 61%, with a blocking of about 20% of the visual response spectrum, resulting in an FOM value of about 3.1.

[0065]

[0096] The filter of this embodiment has the following layer characteristics listed in the following table from the outermost layer (MgF2) to the innermost layer (127 nm thick TiO2). [Table 3]

[0066]

[0097] The filter embodiments described in connection with Figures 8-15 utilized a low refractive index MgF2 layer. Other embodiments may not require this material. For example, Figure 17 illustrates a filter design for one embodiment that blocks approximately 73% of the melanopsin action potential spectrum (or light intensity) and approximately 21% of the visible response light intensity, resulting in an FOM value of approximately 3.5. The layer properties of the filter design illustrated in Figure 17, from outermost to innermost, are listed in the following table: [Table 4]

[0067]

[0098] As mentioned above, it may be desirable to reduce the amount of light reflected from the back side (i.e., the side closest to the user's eye) into the user's eye. This may be achieved with another embodiment of a filter design in which a thin film coating may be added to a tinted lens or substrate. In other embodiments, the substrate may be tinted by impregnation, coating, other tinting techniques, or a combination thereof. The transmittance of light through a thin film coating / tinted substrate combination may be expressed as the product of the transmittance of the thin film coating and the transmittance of the tinted substrate. T(λ)=T film (λ)T tint (λ) (4) The thin film coating is assumed to be applied only to the front surface of the substrate, and the anti-reflective coating (where T≈1) is assumed to be applied to the rear surface of the substrate.

[0068]

[0099] For light entering the rear surface of the substrate, it first passes through the tint, is reflected by a thin film filter on the front surface of the substrate, and then passes through the tint again before illuminating the user's eye. In this case, the reflected light can be written as:

number

[0069]

[0100] At any particular wavelength, the ratio of transmitted to reflected light is This can be set by the transmittance of the coating and the colored portion. For example, if a transmittance of about 20% is desired at a desired wavelength (about 480 nm in this example), only a specific combination of the transmittance of the thin film and the transmittance of the colored portion can be used. Furthermore, if a reflection of about 10% is desired, only one combination of the transmittance of the thin film and the transmittance of the colored portion is allowed. These relationships can be explained as follows:

number

number

[0070]

[0101] The amount of light received by melanopsin cells due to back-reflected light into the user's eye, D, is , can be expressed similarly to the amount of light received by melanopsin cells due to transmitted light as shown in equation (1). D R-melan =∫L(λ)R(λ)M(λ)dλ (8) where L is the light spectrum (in terms of intensity, power, photons / second, etc.), R is the spectral back reflectance, and M is the normalized action potential response spectrum of melanopsin, currently estimated from Figure 1 to be a Gaussian function centered at 480 nm with a full width at half maximum of 52 nm. For generality, we assume L=1 so as not to limit the discussion to any particular light source, although the analysis can be performed for the well-known spectrum of any light source.

[0071]

[0102] The normalized amount of light received by melanopsin cells due to back-reflected light is given by the following equation: It can be calculated.

number

[0072]

[0103] The equivalent and normalized light quantities are calculated relative to the visual response spectrum. obtain. D R-vis =∫L(λ)R(λ)V(λ)dλ (10)

number

[0073]

[0104] The intensity of back-reflected light relative to the action potential spectrum of the melanopsin pathway is given by the formula: (8). The amount of back-reflected light relative to the visual spectrum can be determined using equation (9). The amount of back-reflected light can be used to design and manufacture optical filters. For example, an appropriate level of pigmentation can be selected based on the maximum desired amount of back-reflected light, whether across the action potential spectrum of the melanopsin pathway, across the visual spectrum, or both. Reducing the amount of light received by melanopsin cells and the normalized amount of back-reflected light can reduce the symptoms suffered by photophobic users.

[0074]

[0105] The following table shows, for example, specific transmittance and backside reflectance at about 480 nm: 10A-10C illustrate additional embodiment filter designs using several possible notch and tint transmittance combinations that result in a 480 nm notch. Note that due to the notch response, the transmittance of light outside the notch will be greater than the transmittance of light within the notch, resulting in less back-reflected light than occurs at the center of the notch. However, while these examples are specific to a notch centered around 480 nm, other wavelengths may be selected as described herein.

[0075]

[0106] Table 1 shows the fixed wavelengths (e.g., about 480 nm) or wavelength ranges. Examples are provided in which the transmission through the front side is different while maintaining a back side reflectance of 10%. This value of back side reflectance may be desirable, for example, for therapeutic lenses that may be used in "open" style eyeglass frames, where light is allowed to enter the lens from the top, bottom, and / or sides, entering the back side of the lens and reflecting off the front thin film coating into the user's eye. For other styles of eyeglass frames (e.g., sports glasses, wraparound sunglasses, or other styles of frames), other amounts of back side reflectance may be desirable. [Table 5]

[0076]

[0107] Table 2 provides another embodiment in which greater backside reflectivity is permitted. This design may be more appropriate for "wrap" style eyeglass frames or sports frames that prevent light from entering the eye other than light passing through the front of the lens. [Table 6]

[0077]

[0108] Other embodiment filters may be configured to adjust the transparency of the notch to provide a given backside reflectance value. These embodiments may include fixing the transmittance of the colored portion and adjusting the transmittance of the colored portion. Examples of these embodiments are shown in Table 3 below. [Table 7]

[0078]

[0109] The R values ​​described herein can be used to determine the maximum amount of back-reflected light. For example, an R value of approximately 0.10 can be used as the desired amount of back-reflected light weighted across the melanopsin pathway's action potential spectrum, the visual spectrum, or both. Because the R value is based on the desired wavelength to be attenuated, light of other wavelengths can be attenuated based on a filter designed to achieve an R value equal to or less than the value in the table above. For example, for a wavelength of approximately 480 nm, which has an R value of approximately 0.10, the R value for wavelengths of approximately 470 nm or 490 nm can be less than 0.10, e.g., approximately 0.09. Generally, the R value decreases with wavelength away from the desired notch center wavelength. For clarity, the tables herein list the R values ​​as decimal values, but these values ​​can also be expressed as percentages.

[0079]

[0110] These examples are not intended to limit the suitable combinations for this disclosure. The combinations are not intended to be limiting and are provided only to demonstrate some possible combinations that may be suitable for therapeutic effect. Any number of other combinations are envisioned and may be suitable for different levels of user photosensitivity, for different ailments, for different applications, and for different types of coloring (e.g., gray, FL-41, etc.), as well as for different frame formats.

[0080]

[0111] Manufacturing considerations may also be taken into account when implementing a filter design. For example, material deposition is typically achieved using sputtering, evaporation, or chemical vapor deposition techniques. Deposition conditions can be optimized to minimize stress in the thin film material. High-temperature thermal annealing can often be performed after deposition to relieve stress in the deposited material, but annealing is often not applicable to plastic lenses. Because eyeglass lenses represent curved substrates, achieving a consistent film thickness during deposition can be difficult. To achieve a consistent film thickness, varying the target and source orientation within the deposition system can be used. For plastic lenses, low-temperature deposition can be used, which can be optimized to produce a low-stress film.

[0081]

[0112] The following examples describe optical filter designs that were tested and the results. The notch coating was produced on a polycarbonate or CR-39 plano lens with a scratch-resistant coating. A thin layer of Cr was deposited on the substrate to serve as an adhesion layer in the thin-film stack. The transmission spectrum through an exemplary coated lens is shown in Figure 18A. The notch is centered at approximately 482.9 nm, has a width of approximately 55.5 nm, and has a minimum transmission of approximately 24.5%. The filter of this embodiment blocks approximately 58% of the melanopsin action potential spectrum and approximately 23% across the visible spectrum, resulting in an FOM value of approximately 2.6. In contrast, Figure 18B shows the transmission spectrum of the coated lens using a 620 nm notch filter.

[0082]

[0113] In a preliminary clinical trial, migraine patients were given eyeglasses containing the therapeutic notch coating of FIG. Participants wore the therapeutic lenses for two weeks. All participants reported chronic headaches, defined as headaches on more than 15 days per month, prior to study inclusion. A formal questionnaire, the HIT6, was used to assess the impact of headaches on participants' daily lives, both before and after wearing the therapeutic lenses. The HIT6 scores are tabulated in the following table. There was an average improvement of approximately 6.6%, with a significant improvement in participants' quality of life. [Table 8]

[0083]

[0114] In another embodiment, a thin film notch coating is applied to an FL-41 tinted lens. The transmission and rear reflectance spectra are shown in Figures 19 and 20. Various levels of FL-41 tinting were applied to a tintable scratch-resistant layer (also called a hard coat) on polycarbonate or CR-39 lenses. A multilayer notch filter was then applied to the front of each lens, and a conventional anti-reflection coating was applied to the rear of each lens. As can be seen in Figures 19 and 20, the FL-41 tinting significantly reduced rear reflectance. However, in transmittance, the notch response is red-shifted due to the slope of the FL-41 tinting near 480 nm. This shift can be compensated for, including by using a slightly blue-shifted notch design.

[0084]

[0115] The following table shows the levels of obscuration across the melanopsin spectrum and the visual response spectrum. The formula and FOM value for each color level are listed. Similar results can be expected by using other colorations, such as gray colorations such as BPI's "sun gray." [Table 9]

[0085]

[0116] The coatings described herein may also be combined with other techniques. A filter coating may be added to a tinted lens, photochromic materials may be incorporated, polarization technology may be included, other technologies may be combined, or a combination thereof. Additionally, a combination of filter technologies may be used, such as adding a nanoparticle filter coating over a multi-layer thin film coating. Agents such as electro-optic materials, including electro-optic polymers, liquid crystals, or other electro-optic materials, piezoelectric materials, including piezoelectric ceramics such as PZT, or other piezoelectric materials, may be used.

[0086]

[0117] FIG. 21. Fabricating an optical filter that reduces the frequency and / or severity of photophobia. 21 illustrates an exemplary embodiment of a method 2100. Method 2100 may be used to design a filter according to at least one embodiment described herein. Method 2100 may include determining an appropriate light spectrum, as shown in step 2102. Determining an appropriate light spectrum may include consideration of specific lighting conditions, such as obtaining spectrophotometric measurements of indoor fluorescent lighting and / or computer screens in an office, retail, or home environment, or outdoor lighting, such as sunlight resulting from typical outdoor or sporting activities. As shown in step 2104, the amount of light received by melanopsin cells may be determined (e.g., using Equation 1). As shown in step 2106, the amount of light received across the visual response spectrum may be determined (e.g., using Equation 2). As shown in step 2108, the first and second light amounts may be used to design and manufacture an optical filter. The first and second light amounts may be used to determine a figure of merit (FOM) as described herein. In other embodiments, the amount of light across the visual response spectrum may be considered for one or more portions of the visible spectrum. For example, a greater or lesser range than the entire visual response spectrum may be used.

[0087]

[0118] FIG. 22 shows a method for reducing the frequency and / or severity of photophobia or circadian rhythm 22 illustrates an exemplary embodiment of a method 2200 for adjusting a filter. Method 2200 may be used in connection with at least one embodiment of a filter described herein. Method 2200 may include receiving an amount of light, as shown in step 2202. The received light may include direct or indirect light from one or more light sources. As shown in step 2204, less than a first amount of light weighted across the action potential spectrum of melanopsin cells may be transmitted. As shown in step 2206, a second amount of light weighted across the visual light spectrum may be transmitted. As shown in step 2208, an optical filter may be fabricated using the first and second amounts of light. The first and second amounts of light may be used to determine a figure of merit (FOM), as described herein. Other implementations may include: receiving an amount of light; transmitting an amount of light; transmitting a second amount of light weighted across the visual light spectrum; transmitting a second amount of light; transmitting a first amount of light; and transmitting a second amount of light. The first and second amounts of light may be used to determine a figure of merit (FOM), as described herein. Other implementations may include: receiving an amount of light; transmitting a first amount of light; transmitting a second amount of light; transmitting a second amount of light weighted across the visual light spectrum; transmitting a second amount of light; transmitting a first amount of light; transmitting a second amount of light; transmitting a second amount of light; transmitting a second amount of light weighted across the visual light spectrum; and transmitting a first amount of light; transmitting a second ... In some embodiments, the amount of light across the visual response spectrum may be reduced or separated, for example, a greater or lesser range than the entire visual response spectrum may be used.

[0088]

[0119] In addition to modulating the exposure of melanopsin ganglion cells to light around 480 nm, Clinical trials have demonstrated that attenuation of light at a wavelength of approximately 620 nm may also provide improvement in reducing symptoms related to photosensitivity. Although light wavelengths at approximately 620 nm are not thought to affect melanopsin ganglion cells, attenuation of light at approximately 620 nm has been shown to reduce symptoms of photosensitivity in some individuals, such as pain or discomfort in response to light, and the frequency and / or severity of migraines and other headaches, and may also be effective in treating blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy in some individuals.

[0089]

[0120] In one embodiment, light between about 580 nm and about 650 nm is attenuated. In other embodiments, improvements may be realized by attenuating light between about 600 nm and about 640 nm. In yet other embodiments, improvements may be realized by attenuating light using a filter centered substantially at a wavelength of 620 nm with a full width at half maximum of about 55 nm.

[0090]

[0121] Additionally, the filter may attenuate wavelengths of light in multiple ranges, for example: In one embodiment, the filter may attenuate light at about 620 nm in addition to attenuating light at about 480 nm. In another embodiment, the filter may preferentially attenuate wavelengths of light from about 450 nm to about 510 nm and from about 580 nm to about 640 nm. In yet another embodiment, the filter may attenuate light between about 470 nm to about 490 nm and between about 610 nm to about 630 nm.

[0091]

[0122] Optical filters are fabricated according to the aforementioned processes and using the aforementioned materials. For example, a 620 nm optical filter may include a high-pass filter, a low-pass filter, or an optical notch filter. An optical notch filter may include multiple layers of dielectric materials, nanoparticles dispersed or embedded in a matrix, or combinations thereof. Additionally, any of the foregoing combinations may be used in conjunction with dyes incorporated into the substrate. For example, creating a short-pass or notch filter may involve using alternating layers of high and low refractive index materials. Exemplary low refractive index dielectric materials include MgF2 and SiO2. Exemplary high refractive index materials include metal oxides such as TiO2, Ti3O5, ZrO2, and Ta2O5, as well as Si3N4. Many other suitable materials, including polymer layers, may be used.

[0092]

[0123] It is intended to attenuate wavelengths absorbed by melanopsin ganglion cells Similar to the previous embodiment, an optical filter designed to attenuate wavelengths around 620 nm can be manufactured according to a similar FOM. The amount of light received at around 620 nm, D, can be expressed as: D rec,620 =∫L(λ)T(λ)R 620 (λ)dλ (12) where L is the light spectrum (in terms of intensity, power, photons / second, etc.), T is the spectral transmittance of the filter between the light source and the eye, and R 620 is an ideal response spectrum at about 620 nm, which can be estimated as a Gaussian function centered at 620 nm with a full width at half maximum of 50, 55, or 60 nm, although other values ​​are envisioned and may prove therapeutically effective. For generality, we will assume L=1 so as not to limit the discussion to any particular light source, but the analysis can be performed for any light source with a known spectrum.

[0093]

[0124] Similar amounts of light can be calculated in relation to the visual response spectrum. D vis =∫L(λ)T(λ)V(λ)dλ (13) where V represents the normalized visual response spectrum.

[0094]

[0125] The effect of an optical filter such as a nanoparticle notch filter can be expressed as follows: , the light amount is reduced as explained by taking the ratio of the amount of light calculated with the filter to the amount of light without the filter.

number

[0095]

[0126] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0096]

[0127] FOM comparing light obscuration at approximately 620 nm with obscuration of the visual response spectrum can also be defined.

number

[0097]

[0128] Optical filters account for the attenuation of light to which melanopsin cells are sensitive. The optical filter may include a multilayer dielectric film similar to those described above, or the optical filter may include a nanoparticle-based optical filter, a color filter, a tint, a resonant waveguide mode filter, a rugate filter, or any combination thereof. Nanoparticle-based optical notch filters may include nanoparticles dispersed on the surface of a host material or embedded in a host material. Thus, such filters may be used in a substantially transparent host material, such as eyeglass lens material, or simply affixed to the surface. For example, a filter may be disposed on the surface of an eyeglass lens. The nanoparticle-based optical notch filter can be configured to attenuate light approaching a user's eye. In other applications, the filter can be placed directly on a light source, e.g., an electronic display such as a computer screen, or a light source such as a light bulb, and the attenuation of light by the nanoparticle-based notch filter can be tuned by the shape of the nanoparticles, the amount or density of nanoparticles on or embedded in the host material, the composition of the nanoparticles, the size of the nanoparticles, and the refractive index of the host material. Thus, the attenuation spectrum of a nanoparticle-based optical notch filter can be tuned to a specific curve by selecting materials and profiles that center the curve at a desired wavelength and produce an attenuation curve with a maximum attenuation at a desired wavelength value and an appropriate shape and full width at half maximum.

[0098]

[0129] For example, increasing the refractive index of the nanoparticle matrix increases the refractive index of the solid particles and the core-shell Similarly, using longer particle sizes, including particles, and / or other metals, can shift the extinction spectrum toward longer wavelengths. The extinction spectrum changes because the extinction is due, at least in part, to localized surface plasmonic resonance (LSPR). Scattering due to LSPR is proportional to the relative refractive index of the host material. Therefore, when the refractive index of the host material increases, not only does the extinction spectrum red-shift, but the amount of scattering, and therefore the amount of light attenuation, also increases.

[0099]

[0130] The location and amount of scattering due to LSPR is determined, at least in part, by the particle and the matrix. The refractive index depends on the relative refractive index between the two materials. Therefore, the relative refractive index can also be modified by changing the composition of the nanoparticle. Nanoparticles can be solids made of a single material or core-shell configurations, with a core of one material and a shell of a second material. In either case, the material can be a single element, a compound, or an alloy. As previously mentioned, nanoparticles can include metal nanoparticles (e.g., Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g., TiO2, Ta2O5, etc.), semiconductor nanoparticles or quantum dots (e.g., Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell particles with one material in the core and another material acting as the shell, other nanoparticles, or combinations thereof. For example, increasing the Ag ratio in an Ag / Al alloy solid nanoparticle can increase the amplitude and red-shift the extinction curve for that nanoparticle.

[0100]

[0131] In addition, the nanoparticles used may be circular, elliptical, rectangular, hexagonal, octagonal, or Cross sections may include other polygonal shapes. Spherical particles have the most distinct spectra, with a single, narrow main peak that allows for optimization using size and compositional variations. However, it is possible to use a combination of particles with other shapes to create a desired filter spectrum. For example, the extinction spectrum of a 40 nm spherical nanoparticle filter can be broadened simply by introducing cubic or octahedral nanoparticles of comparable dimensions.

[0101]

[0132] In contrast, the extinction curves of core-shell nanoparticles vary with the relative thickness of the core and shell. The optical filter can be adjusted by varying the thickness of the Ag shell relative to the dimensions of the SiO2 core. For example, decreasing the thickness of the Ag shell relative to the dimensions of the SiO2 core can reduce the full width at half maximum of the attenuation spectrum. The shape of these particles can be spherical, ellipsoidal, another shape, or a combination thereof. The shape of the particles can also affect the shape and amplitude of the attenuation curve. In one embodiment, the optical filter comprises spherical core-shell nanoparticles. In another embodiment, the spherical core-shell nanoparticles comprise an Ag shell and a Si core. In yet another embodiment, the spherical Ag / Si core-shell nanoparticles comprise an Ag shell with a radial thickness of 45 nm and a Si core with a radius of 15 nm.

[0102]

[0133] FIG. 23 illustrates a filter used in conjunction with a multi-layer thin film filter to form a composite filter 2300. 23A shows a nanoparticle-based optical filter that can be used in conjunction with a first filter. A first filter can attenuate light in a first wavelength range, thereby substantially reducing or eliminating those wavelengths in the light spectrum that enters the second filter. In the illustrated embodiment, ambient light 2302 is a thin The light may enter a filter containing nanoparticles 2304, which may be disposed on or embedded within a matrix 2306 disposed on the surface of the membrane filter 2308. Alternatively, or in addition, a thin film filter and a nanoparticle-based filter may be disposed on opposite sides of a substrate, such as a lens of eyeglasses. In another embodiment, the nanoparticles may be embedded within a thin film filter, and one or more layers of the thin film may be the matrix for the nanoparticle-based filter. The ambient light 2302 entering the matrix 2306 with embedded nanoparticles 2304 may be sunlight. The attenuated light 2310 entering the thin film filter 2308 may include a reduced amount of light in the range attenuated by the nanoparticles 2304. The filtered light 2312 exiting the composite filter 2300 may be attenuated in two wavelength ranges. Similarly, a "two-notch" filter may be implemented entirely through the use of multi-layer thin film coatings.

[0103]

[0134] FIG. 24 shows a composite optical filter that reduces the frequency and / or severity of photophobia. 24 illustrates one embodiment of a method of manufacturing 2400. Method 2400 may be used to design a composite filter of at least one embodiment described herein. Method 2400 may include determining an appropriate light spectrum, as shown in step 2402. Determining an appropriate light spectrum may include consideration of specific lighting conditions, such as taking spectrophotometric measurements in situations such as indoor fluorescent lighting and / or computer screens in an office, retail, or home environment, or outdoor lighting such as sunlight resulting from normal outdoor or sporting activities.

[0104]

[0135] As shown in step 2404, a first amount of light received by the subject is calculated (e.g., by the formula As shown in step 2406, a second amount of light received by the human eye at a wavelength of approximately 620 nm may be estimated (e.g., using Equation 12). As shown in step 2408, a third amount of light received across the visual response spectrum may be determined (e.g., using Equation 13). As shown in step 2410, an optical filter may be designed and manufactured using the first amount of light, the second amount of light, and the third amount of light. As described herein, each of the first amount of light and the second amount of light may be used in conjunction with the third amount of light to determine a respective figure of merit (FOM). In other embodiments, light amounts across the visual response spectrum may be considered for one or more portions of the visible spectrum. For example, a range greater than or less than the entire visual response spectrum may be used.

[0105]

[0136] FIG. 25 shows a method for reducing the frequency and / or severity of photophobia or altering the circadian rhythm. 25 illustrates one embodiment of a method 2500 for using a composite filter to modulate light. Method 2500 may be used in connection with at least one embodiment of the composite filter described herein. Method 2500 may include receiving an amount of light, as shown in step 2502. The received light may include direct or indirect light from one or more light sources. As shown in step 2504, a first amount of light preferentially attenuated across the action potential spectrum of melanopsin cells may be transmitted. As shown in step 2506, a second amount of light preferentially attenuated in a wavelength range at about 620 nm may be transmitted. As shown in step 2508, a third amount of light is then transmitted to the human eye. In other embodiments, the amount of light across the visual response spectrum may be reduced or separated. For example, a range greater than or less than the entire visual response spectrum may be used.

[0106]

[0137] A study demonstrating the benefits of attenuating light near approximately 480 nm and 620 nm Efficacy studies were conducted. The preliminary study included a prospective double-masked crossover clinical trial to determine the effectiveness of customized thin-film eyeglass coatings in treating chronic migraines. Subjects wore two different eyeglasses during the study, one coating of which was a notch filter at 480 nm. The other coating was a notch filter at 620 nm. Typical transmission spectra of gray-tinted lenses containing the various coatings used in this study are shown in Figures 26A and 26B. The 480 nm notch filter shown blocks approximately 68% of light absorption by melanopsin and 42% of visible light. The 620 nm notch filter shown blocks approximately 66% of light absorption centered at 620 nm with a width of approximately 55 nm and blocks approximately 42% of visible light. The 480 nm filter used in the study provided an average of 68 ± 6% blocking at approximately 480 nm and an average of 44 ± 4% visible blocking. The 620 nm filters used in the study provided an average of 67 ± 2% blocking at approximately 620 nm and an average of 43 ± 4% visible blocking. Neither the subjects nor the clinical coordinators knew which lenses contained a 480 nm notch filter and which contained a 620 nm notch filter. Subjects in the study had to have a diagnosis of chronic migraine, meaning that they had at least 15 headache days per month. Those with at least 15 headache days per month were considered to be migraine sufferers with the most severe symptoms.

[0107]

[0138] To assess the effectiveness of the intervention, a six-question questionnaire was used as the primary outcome measure. The Headache Impact Test (HIT-6), which is based on the HIT-6 questionnaire, was selected. The HIT-6 is a six-question instrument designed and validated to assess the impact of headaches on a person's life. Scores are continuous, ranging from a minimum of 36 to a maximum of 78. A score below 50 represents little impact of headaches on a person's life, a score of 50-55 represents "some impact," a score of 56-59 represents "considerable impact," and a score above 60 corresponds to a "very severe impact" of headaches.

[0108]

[0139] The subjects first underwent a four-week "pre-cleaning" period without wearing the test lenses. This period served to determine the subject's baseline headache profile. Subjects were first randomized using block randomization to choose which lenses to wear. Subjects were instructed to wear their glasses 24 / 7 for two weeks. Subjects then underwent a two-week "cleaning" period during which no test lenses were worn. After that, subjects wore different lenses for another two weeks. Finally, subjects underwent a final "post-cleaning" period during which no test lenses were worn, which determined the "end point" for headache profile.

[0109]

[0140] There is a considerable amount of variability in the frequency and severity of headaches. This variability can occur even within the same patient. Due to this variability, a "pre-cleansing" period and a "post-cleansing" period were added. These additional periods, during which the test lenses were not worn, minimized the impact of "baseline variability" among the study subjects.

[0110]

[0141] The HIT-6 questionnaire was administered before the study and after each period of the study. Six questionnaires were administered to each surgeon. Initially, 48 participants enrolled in the study, with 37 completing the full test series. The baseline HIT-6 score for the 37 subjects who completed the study was 64.5. Thirty-three of the 37 subjects (89%) achieved a baseline HIT-6 score of 60 or higher. Based on the interpretation of the HIT-6, these 33 subjects suffered from headaches that "very severely impacted" their lives. Both the 480nm and 620nm filter lenses demonstrated statistically significant reductions in HIT-6 scores.

[0111]

[0142] Of the 37 participants who completed the study, 9 subjects were wearing the 480 nm lens. 10 subjects were able to exit the HIT-6 category of "very severely affected" while wearing the 480 nm lenses, 5 subjects were able to exit this category while wearing the 620 nm lenses, and 5 subjects were able to exit this category while wearing either of these lenses. 10 subjects experienced at least a 6-point improvement on the HIT-6 while wearing the 480 nm lenses, 10 subjects experienced at least a 6-point improvement on the HIT-6 while wearing the 620 nm lenses, and 3 subjects were able to exit this category while wearing either of these lenses. Patients who wore either of these lenses experienced an improvement of at least 6 points on the HIT-6. This analysis shows that wearing either the 480nm or 620nm spectacle lenses resulted in a statistically significant reduction in the HIT-6. However, there was no substantial difference when comparing the effect of the 480nm lenses with the 620nm lenses (p=0.195).

[0112]

[0143] Percentage of days with severe headaches and the number of days for which activities had to be changed or Secondary outcomes collected from the diary, including the percentage of days the surgeon needed to sleep and the percentage of days requiring abortive medication, behaved similarly to the primary outcome for either the 480 nm or 620 nm spectacle lenses. That is, subjects experienced significant reductions in these parameters while wearing either the 480 nm or 620 nm lenses. For all three outcomes, there was no substantial difference in the effect of the 480 nm lenses compared with the 620 nm lenses.

[0113]

[0144] Melanopsin in melanopsin ganglion cells is a bistable pigment. can be isomerized during exposure to light of a particular wavelength. Figure 27 is a graph 2700 that schematically illustrates the cyclic isomerization of a bistable dye when the dye is exposed to light of different wavelengths. The bistable dye can include a first isoform that exhibits a first absorption spectrum 2702. The first absorption spectrum absorbs a first wavelength 2704. The first isoform of the bistable dye can react with the first wavelength 2704. The first wavelength 2704 can isomerize the bistable dye and trigger a phototransduction cascade in an associated cell or membrane. In one embodiment, the bistable dye can be melanopsin, and exposure to the first wavelength 2704 can trigger a phototransduction cascade in a melanopsin ganglion cell. Exposure to the first wavelength can isomerize the bistable dye from the first isoform to a second isoform. The first isoform can be the active 11-cis isoform of melanopsin. The second isoform may be an inactive metamelanopsin isoform. Isomerization of the active 11-cis isoform may result in a phototransduction cascade.

[0114]

[0145] The second isoform may exhibit a second absorption spectrum 2706. Absorption spectrum 2706 may absorb at a second wavelength 2708. A second isoform of the bistable dye may react with the second wavelength 2708. In one embodiment, the first isoform may be an active isoform of the bistable dye and the second isoform may be an inactive isoform of the bistable dye. In other embodiments, the first isoform may be an inactive isoform of the bistable dye and the second isoform may be an active isoform of the bistable dye. In yet other embodiments, the first isoform may be an active isoform of melanopsin and the second isoform may be an inactive isoform of melanopsin.

[0115]

[0146] Figure 28 shows the active and inactive absorption spectra of melanopsin. 28 shows a graph 2800 of the active absorption spectrum 2802 and the inactive absorption spectrum 2804 corresponding to the active isoform of melanopsin and the inactive isoform of melanopsin, respectively. "Active" and "inactive" refer to the biological activity of the pigment, and should be understood as the ability of the pigment to contribute to the human photophobia response, rather than the ability of the pigment to absorb light. The active absorption spectrum 2802 may have a maximum at approximately 484 nm. The inactive absorption spectrum 2804 may have a maximum at approximately 587 nm.

[0116]

[0147] The inactive isoform of melanopsin follows the inactive absorption spectrum2804. The inactive isoforms of melanopsin may absorb wavelengths of light that are different from the active form. Light absorbed by the inactive isoforms of melanopsin may contribute to the conversion of the inactive isoforms to the active form of melanopsin. The active form of melanopsin may contribute to the photophobia response in humans. In at least one embodiment, the attenuation of light absorbed by the inactive isoforms interferes with the isomerization of melanopsin, which may reduce symptoms of photosensitivity in some individuals, such as pain or discomfort in response to light, and the frequency and / or severity of migraines and other headaches, and may also be effective in treating blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy in some individuals.

[0117]

[0148] melanopsin ganglion cells to light around 480 nm and / or 620 nm In addition to adjusting exposure, attenuation of light at the absorption maximum of the inactive absorption spectrum in the case of the inactive isoform of melanopsin may also provide improvement in reducing symptoms related to photosensitivity. For example, an optical filter centered at a wavelength of approximately 590 nm may attenuate light absorbed by the inactive isoform of melanopsin.

[0118]

[0149] In one embodiment, light between about 560 nm and about 620 nm is attenuated. In another embodiment, improvements may be realized by attenuating light between about 570 nm and about 610 nm. In yet another embodiment, improvements may be realized by attenuating light using a filter centered substantially at a wavelength of 590 nm with a full width at half maximum of about 50 nm.

[0119]

[0150] Additionally, the filter may attenuate wavelengths of light in multiple ranges, for example: In one embodiment, the filter may attenuate light absorbed by the inactive isoform of melanopsin and light absorbed by the active isoform of melanopsin. In one embodiment, the filter may attenuate light at about 590 nm in addition to attenuating light at about 480 nm. In another embodiment, the filter may preferentially attenuate light wavelengths from about 450 nm to about 510 nm and from about 560 nm to about 620 nm. In yet another embodiment, the filter may attenuate light between about 470 nm to about 490 nm and between about 580 nm to about 600 nm.

[0120]

[0151] Similar to the 480nm and 620nm filters mentioned above, this filter also filters out 590nm light. Optical filters that can be attenuated may include high-pass filters, low-pass filters, optical notch filters, or combinations thereof. Optical notch filters may include multiple layers of dielectric materials, nanoparticles dispersed or embedded in a matrix, or combinations thereof. Additionally, any of the foregoing combinations may be used in conjunction with dyes incorporated into the substrate. For example, creating a short-pass or notch filter may involve using alternating layers of high and low refractive index materials. Exemplary low refractive index dielectric materials include MgF2 and SiO2. Exemplary high refractive index materials include metal oxides such as TiO2, Ti3O5, ZrO2, and Ta2O5, as well as Si3N4. Many other suitable materials, including polymer layers, may be used.

[0121]

[0152] It attenuates the wavelengths absorbed by the active isoform of melanopsin mentioned above. As with the embodiment intended to be used, an optical filter designed to attenuate wavelengths around 590 nm can be fabricated according to a similar FOM. The amount of light received at about 590 nm, D, can be expressed as: D rec,590 =∫L(λ)T(λ)R 590 (λ)dλ (15) where L is the light spectrum (in terms of intensity, power, photons / second, etc.), T is the spectral transmittance of the filter between the light source and the eye, and R 590 is an ideal response spectrum at about 590 nm, which can be estimated as a Gaussian function centered at 590 nm with a full width at half maximum of 50, 55, or 60 nm, although other values ​​are envisioned and may prove therapeutically effective. For generality, we assume L=1 so as not to limit the discussion to any particular light source, although the analysis can be performed for any light source with a known spectrum.

[0122]

[0153] Similar amounts of light can be calculated in relation to the visual response spectrum. D vis =∫L(λ)T(λ)V(λ)dλ (16) where V represents the normalized visual response spectrum.

[0123]

[0154] The effect of an optical filter such as a nanoparticle notch filter can be expressed as follows: , reducing the amount of light, as explained by taking the ratio of the amount of light calculated with the filter to the amount of light without the filter.

number

[0124]

[0155] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0125]

[0156] FOM comparing light obscuration at approximately 590 nm with obscuration of the visual response spectrum can also be defined as follows:

number

[0126]

[0157] FIG. 29 illustrates a method 2900 for reducing symptoms associated with photophobia. 29. The method includes receiving light 2902, attenuating a first wavelength 2904, and optionally attenuating a second wavelength 2906. The attenuation of the first wavelength may subsequently disrupt bistable dye cycling 2908, as described with reference to FIG. 27. In one embodiment, the first wavelength may be determined by a maximum in the active or inactive absorption spectrum of the bistable dye. In another embodiment, the first wavelength may be determined by a maximum in the active or inactive absorption spectrum of the bistable dye, as described with reference to FIG. 28. The first wavelength may be determined by the maximum of the active absorption spectrum 2802 or the maximum of the inactive absorption spectrum 2804 of melanopsin, as described above. In yet another embodiment, the first wavelength may be 480 nm. In another embodiment, the first wavelength may be 590 nm.

[0127]

[0158] Attenuating a wavelength means that that wavelength or wavelengths are less visible than the rest of the visible spectrum. " should be understood to mean preferentially attenuating a range that includes that wavelength. For example, attenuating a 590 nm wavelength may include transmitting less light at or about 590 nm wavelength than other light in the visible spectrum. In another example, attenuating a 590 nm wavelength may include blocking substantially all of the light at or about 590 nm wavelength and transmitting other light in the visible spectrum.

[0128]

[0159] Attenuating the second wavelength 2906 is a different wavelength than the first wavelength being attenuated. The method may include attenuating a portion of the second wavelength. In one embodiment, the second wavelength may be determined by a maximum in the active or inactive absorption spectrum of the bistable dye. In another embodiment, the first wavelength may be determined by a maximum in the active absorption spectrum 2802 of melanopsin or a maximum in the inactive absorption spectrum 2804 of melanopsin, as described in connection with FIG. 28 . In yet another embodiment, the first wavelength may be 480 nm. In another embodiment, the first wavelength may be 590 nm.

[0129]

[0160] Attenuating the first wavelength 2904 and, optionally, attenuating the second wavelength 2906 Attenuating the first wavelength 2904 can disrupt bistable dye cycling. Attenuating the first wavelength 2904 can inhibit isomerization of the bistable dye from a first isoform to a second isoform. The first isoform can be an active or an inactive isoform. Attenuating the second wavelength 2906 can inhibit isomerization of the bistable dye from the second isoform back to the first isoform.

[0130]

[0161] Optical filter that can attenuate light with a wavelength of 590 nm or approximately 590 nm The filter may be fabricated and / or tuned by any of the aforementioned processes to form a low-pass filter, a high-pass filter, or an optical notch filter that preferentially attenuates 590 nm light. The filter may include multilayer dielectrics, nanoparticle-buried coatings, color filters, tints, resonant guided-wave mode filters, rugate filters, and any combination thereof. The filter may further include nanoparticle-buried coatings, such as metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material acting as the shell.

[0131]

[0162] The optical filters of the present disclosure remove specific colors in the visible spectrum, When viewing through a filter, a coloration may appear. The standard method for quantifying this coloration is to use the CIE chromaticity diagram, typically referencing the 1931 Standard Observer, although other versions of the CIE color space may be used (such as the 1964 10° chromaticity coordinates or coordinates based on Stiles-Burch data, which yield substantially similar results), where two chromaticity coordinates, "x" and "y," map to human color vision. There is a point on the CIE chromaticity diagram called the achromatic point (x = y = l / 3), where the perceived color is white (or gray, depending on the transmitted lightness, or luminance, level Y). Ideally, an optical filter for viewing would have chromaticity coordinates x = y = l / 3.

[0132]

[0163] Chromaticity coordinates are calculated using color-matching functions based on physiological responses to various wavelengths of light. This is achieved via the color-matching function (CMF). Again, the CMFs usually refer to the 1931 2° data, but other CMFs that give substantially similar results may be used (such as the 1964 10° color matching functions, or CMFs based on the Stiles-Burch data). The following functions can serve as weighting factors for the input spectrum:

number

number

number

number

number

number

[0133]

[0164] The chromaticity coordinates can then be calculated from the tristimulus values:

number

[0134]

[0165] As an example, FIG. 31 shows a 480 nm notch filter according to the present disclosure. , where the product represents the color matching function modified by the presence of the filter

number

number

number

[0135]

[0166] By adding a second notch at a wavelength around 590 nm, the filter The chromaticity coordinates of the filter can be adjusted towards the achromatic point, making the filter appear gray. One such embodiment is shown in Figure 32, where the 480 nm and 590 nm notches are approximated as Gaussian functions (with center wavelengths of 480 nm and 590 nm, respectively; full widths at half maximum of 31 nm and 50 nm; notch depths of 0.625 and 0.41; an overall uniform reduction of 10% across the visible spectrum representing a light gray coloration reduces the overall transmittance, but this does not affect the chromaticity coordinates).

[0136]

[0167] The 480nm notch alone is X=91.8, Y=89.9, and Z=68. It has a tristimulus value of 5, with chromaticity coordinates x=0.367 and y=0.359, also producing a yellow hue. By adding a 590 nm notch, the tristimulus values ​​are nearly equalized at X=68.1, Y=68.4, and Z=68.2, where the chromaticity coordinates are now x=0.3327 and y=0.3341, thereby achieving a nearly achromatic condition.

[0137]

[0168] Based on adjusting the width, depth, shape, and position of the two notches, a large number of Other combinations are possible. For example, since blocking light near wavelengths of 480 nm and 590 nm is known to reduce light sensitivity and migraines, one filter design procedure would be to first design a therapeutic 480 nm notch (i.e., to achieve a certain amount of blocking across the melanopsin action potential spectrum Rmelan, i.e., wavelength range, or to achieve a specific FOM, as taught by the present disclosure), and then add a second notch at about 590 nm to achieve the desired achromatic condition. Similarly, by using a simplified Gaussian notch filter centered at 480 nm with a full width at half maximum of 52 nm and a depth of 0.625, a color-balancing notch centered at 584 nm with a width of 51 nm and a depth of 0.57 can be used to achieve chromaticity coordinates of x=0.3332 and y=0.338.

[0138]

[0169] In another embodiment, a color balancer having a width of 67 nm and a depth of 0.47 nm is approximately 587 nm. A single notch can be used to achieve x=0.3323 and y=0.3340. Other filter design procedures are also contemplated, such as first designing a therapeutic notch at 590 nm (i.e., designing to achieve a constant amount of blocking across the R590 response function or wavelength range, or to achieve a specific FOM, as taught by the present invention), and then color balancing with a second notch at about 480 nm; designing and adjusting the width and depth of both the 480 nm and 590 nm notches to simultaneously approach the desired achromatic condition and achieve a constant cumulative amount of light blocking across the R590 and R590 response functions, or achieve a specific FOM taking into account blocking within and outside these regions.

[0139]

[0170] As used herein, "approximately" and "about" The terms "approximately," "near," and "substantially" refer to an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms "approximately," "about," and "substantially" can refer to an amount that is less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the stated amount.

[0140]

[0171] While the present invention is described in connection with the above embodiments, it should be noted that these descriptions are not intended to limit the scope of the invention to the specific forms described; rather, these descriptions are intended to cover alternatives, modifications, and equivalents that may fall within the scope of the present invention. Any element of the above embodiments may be combined with any other element of the above embodiments. For example, any of the above manufacturing methods or light attenuation methods may be combined with the described optical filters and associated wavelengths. Thus, the scope of the present invention fully encompasses other embodiments that may become apparent to those skilled in the art, and the scope of the present invention is limited only by the appended claims. [Form 1] 1. A device for reducing the frequency and / or severity of photophobia, including migraine headaches, by controlling the exposure of melanopsin ganglion cells in the retina to light in the visible spectral range of 400 nm to 700 nm, said device comprising: a fraction of light transmission that is less than a magnitude Tmelan, averaged over wavelengths between about 454 nm and about 506 nm; the fraction of light transmission having a value greater than magnitude Tvis1, averaged over wavelengths in the range of the visible spectrum that is less than about 454 nm; the fraction of light transmission having a value greater than the magnitude Tvis2, averaged over wavelengths within the visible spectrum greater than about 506 nm; an optical filter configured to have Equipped with The ratio including the percentage of light transmission may be defined as a figure of merit (FOM),

number

number

number

number

number

Claims

1. 1. A device for reducing the frequency and / or severity of photophobia, including migraine headaches, by controlling exposure of cells in the retina to light in the visible spectral range of 400 nm to 700 nm, said device comprising an optical filter; The optical filter is an optical notch at a wavelength of 480 nm having a full width at half maximum of 31 nm and chromaticity coordinates of x=0.367 and y=0.359, which produces a yellow hue; an optical notch at a wavelength of 590 nm that has a full width at half maximum of 50 nm and produces a gray coloration, the optical notch at a wavelength of 590 nm having, by addition, chromaticity coordinates of x=0.3327 and y=0.3341; A device wherein the combined chromaticity coordinates of said optical notches are within the range of x=0.33±0.02 and y=0.33±0.02, whereby the yellow hue and gray coloration balance each other to produce an achromatic condition.

2. The device of claim 1, wherein the chromaticity coordinates of the optical filter are x = 0.3327 and y = 0.3341.

3. The device of claim 1, wherein the optical notch at 480 nm has a depth of 0.

625.

4. The device of claim 1, wherein the optical notch at 590 nm has a depth of 0.

41.

5. 1. A device for reducing the frequency and / or severity of photophobia, including migraine headaches, by controlling exposure of cells in the retina to light in the visible spectral range of 400 nm to 700 nm, said device comprising an optical filter; The optical filter is an optical notch at a wavelength of 480 nm having a full width at half maximum of 52 nm and chromaticity coordinates that produce a yellow hue; an optical notch at a wavelength of 584 nm having a full width at half maximum of 51 nm and chromaticity coordinates that produce a gray coloration; A device wherein the combined chromaticity coordinates of said optical notches are within the range of x=0.33±0.02 and y=0.33±0.02, whereby the yellow hue and gray coloration balance each other to produce an achromatic condition.

6. The device of claim 5, wherein the chromaticity coordinates of the optical filter are x = 0.3332 and y = 0.

338.

7. The device of claim 5, wherein the optical notch at 480 nm has a depth of 0.

625.

8. An apparatus as described in claim 5, wherein the optical notch at 584 nm has a depth of 0.

57.

9. 1. A device for reducing the frequency and / or severity of photophobia, including migraine headaches, by controlling exposure of cells in the retina to light in the visible spectral range of 400 nm to 700 nm, said device comprising an optical filter; The optical filter is an optical notch at a wavelength of 480 nm having a full width at half maximum of 52 nm and chromaticity coordinates that produce a yellow hue; an optical notch at a wavelength of 587 nm having a full width at half maximum of 67 nm and chromaticity coordinates that produce a gray coloration; A device wherein the combined chromaticity coordinates of said optical notches are within the range of x=0.33±0.02 and y=0.33±0.02, whereby the yellow hue and gray coloration balance each other to produce an achromatic condition.

10. The device of claim 9, wherein the chromaticity coordinates of the optical filter are x=0.3323 and y=0.3340.

11. The device of claim 9, wherein the optical notch at 480 nm has a depth of 0.

625.

12. The device of claim 9, wherein the optical notch at 587 nm has a depth of 0.47.

Images