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

Abstract

Controlling the effects of light in a subject. More particularly, methods, systems, and devices are provided for reducing the frequency and / or severity of photophobia. [Solution] The optical filter is configured to transmit less than a first amount of light at a particular wavelength and to transmit more than a second amount of light weighted across the visual spectral response.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. patent application Ser. No. 14 / 338,182, entitled "METHODS, SYSTEMS, AND APPARATUS FOR REDUCING THE FREQUENCY AND / OR SEVERITY OF PHOTOPHOBIC RESPONSES OR FOR MODULATING CIRCADIAN CYCLES," filed Jul. 22, 2014. All of the foregoing applications are incorporated herein by reference in their entireties.

[0002]

[0002] Photophobia, or photosensitivity, 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 photophobia responses or for modulating the circadian cycle. [Background technology]

[0003]

[0003] The retina of the eye contains a variety of 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]

[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 adjusting environmental light by tinting eyeglasses 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. September 1991;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. May 2009;116(5):997-1001 PMID 19410958, both of which are incorporated herein by reference in their entirety. In addition to pain transmission pathways, melanopsin ganglion cells are also connected to the suprachiasmatic nucleus, where they are involved in the entrainment of circadian rhythms. 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 by reference in its entirety.

[0005]

[0005] All animals have an endogenous "clock" that synchronizes them to the 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 body 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 rods and cones of the eye. Rhodopsin 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 by reference in its entirety. Summary of the Invention [Problem to be solved by the invention]

[0007]

[0007] It is therefore 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 responses. 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 around 480 nm and are involved in pain pathways in humans, it is desirable to control the painful effects caused by certain types of light. For example, stimulation of melanopsin ganglion cells can affect the frequency and / or severity of photophobic responses, so in some situations it may be beneficial to reduce direct light stimulation of these cells, or in other situations to reduce exposure to light that is not directly related to stimulation of these cells. These photophobic responses are associated with migraines, photosensitivity associated with concussion or traumatic brain injury, photosensitive epilepsy, and benign idiopathic blepharospasm. Melanopsin ganglion cells are also involved in circadian cycles. Thus, methods, systems, and devices are provided for reducing the frequency and / or severity of photophobia and / or modulating 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 cycle is described. The device includes an optical filter configured to transmit less than a first amount of light weighted across the absorption spectrum of a bistable isoform of melanopsin and to transmit more than a second amount of light weighted across the visual spectral response. Illustratively, the light spectrum associated with the absorption spectrum of an active isoform of melanopsin is at wavelengths near 480 nm, and the light spectrum associated with the absorption spectrum of an 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 entirety of the light weighted across the absorption spectrum of one or both of the bistable isoforms of melanopsin. In a different embodiment, the second amount of light is substantially the entirety of the light weighted across a spectrum outside the absorption spectrum of one or both of the bistable isoforms of melanopsin and / or weighted across the visual response spectrum. In yet another embodiment, the ratio of the attenuation of a first amount of light weighted across the absorption spectrum of one or both bistable isoforms of melanopsin to the attenuation of a 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 in 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 includes 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 includes 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 includes 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, such as a retinal ganglion cell or other cell of the subject, (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 a 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 may 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, greater than about 3.3. In other embodiments, other figures of merit may be used.

[0015] In some embodiments, the first amount of light defines a spectral width centered at the median absorption spectrum of one or both bistable isoforms of melanopsin. In other embodiments, the first amount of light and the second amount of light are determined based on characteristics of the ambient light. In yet another embodiment, the first amount of light and the second amount of light 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 that includes an impregnated or coated color.

[0017]

[0017] In one embodiment, a system for reducing the frequency and / or severity of photophobia or modulating circadian cycle 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 transmit 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 manufacturing 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 a visual response spectrum is determined. The first amount of light and the second amount of light are used to manufacture an optical filter.

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

[0021] In some embodiments, the optical filter is a notch filter. In other embodiments, the notch filter is configured to block light incident at a non-normal angle of incidence. In yet another embodiment, the notch filter is configured to block light incident at a plurality of 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 includes a filter notch that attenuates light over a spectral width.

[0022] In some embodiments, producing an optical filter includes using multilayer dielectrics, nanoparticle embedded coatings, color filters, tinting, resonant waveguide mode filters, rugate filters, and any combination thereof. In another embodiment, the nanoparticle embedded 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 acting as the shell. In another different 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 TiO 2 , Ta 2 O 5 In yet another embodiment, the semiconductor nanoparticles or quantum dots comprise 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 embedded coating is spherical, elliptical, or another shape. In some embodiments, the extinction spectrum of the embedded nanoparticles is determined utilizing 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 of the bistable isoforms of melanopsin; 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 of the bistable isoforms of melanopsin disrupts isomerization of one or both of the bistable isoforms of melanopsin.

[0024]

[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 description of the drawings]

[0025] [Figure 1]

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

[0026] FIG. 1 shows the measured transmission spectrum of an exemplary FL-41 35 filter across the effective action potential spectrum of melanopsin. [Diagram 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. [Diagram 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 illustrates an exemplary filter using multi-layer 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. 13 shows the measured transmission spectrum of a filter of another embodiment across the “effective action potential spectrum” of melanopsin. [Figure 12]

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

[0037] FIG. 13 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. 13 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. 13 shows the measured transmission spectrum of yet another embodiment of a filter, excluding the low refractive index MgF2 layer, across the “effective action potential spectrum” of melanopsin. [Figure 18]

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

[0043] FIG. 1 shows measured transmission spectra of several embodiment filters centered at about 480 nm with various 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 severity of photophobia or modulating circadian cycle. [Diagram 23]

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

[0048] 1 illustrates one embodiment of a method for making a composite optical filter. [Diagram 25]

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

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

[0051] FIG. 1 shows a schematic diagram of 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 isomerization of one or both bistable isoforms of melanopsin. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026]

[0054] 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. Thus, the specific details disclosed herein are not intended to be limiting, but rather as representative basis for teaching those skilled in the art how to utilize the present invention in virtually any system, structure, or method.

[0027]

[0055] The present invention relates to controlling the effects of light on a subject. Some applications of the present invention include reducing the frequency and / or severity of photophobia or modulating circadian rhythms. The present invention relates to a method, a system, and an apparatus.

[0028]

[0056] Different people experience photophobia in different ways. The wavelengths that cause adverse reactions to light and the associated transmission pathways 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 about 480 nm. In some people, this may be related to the person's neurological symptoms of photosensitivity. Controlling exposure to light around 480 nm wavelengths may be beneficial for these people, reducing or preventing the person's neurological symptoms of photosensitivity. Alternatively, or in addition, adjusting exposure to the same light may also help control the person's circadian rhythm. In the same or other people, adjusting eye exposure to light around 620 nm or other wavelengths may also be beneficial in reducing or preventing the neurological symptoms of photosensitivity, or in controlling the person'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 other wavelengths of light 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 other examples, similar filters and methods can be used to attenuate light at or about 590 nm.

[0029]

[0057] Because melanopsin ganglion cells are believed to be responsible for photophobia and the onset 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). FIG. 1 shows an exemplary unit-normalized measured action potential spectrum of melanopsin cells and a Gaussian fit to the measured data points. This Gaussian fit may be used in at least one embodiment of a filter design, but this Gaussian fit should not be taken 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 through 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]

[0058] 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 in this application may also be used to manipulate the body's circadian system.

[0031]

[0059] Embodiments of optical filters are described that block specific portions of the optical spectrum suspected of causing and / or exacerbating these photophobic reactions. These filters may be applied to eyewear (such as glasses, 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 are suitable for use with crown glasses (including BK7), flint glasses (including BaF 8 SiO 2, plastics (such as polycarbonate, CR-39, and trivex), other substrates, and combinations thereof.

[0032]

[0060] While most of the description focuses on preventing photophobia, the systems, methods, and devices described herein are also applicable to regulating circadian rhythms. For example, these The filters can be used to manipulate the body's circadian system by businesspeople, athletes, and others who travel between different time zones, or who wish to manipulate the body's circadian system. In one example, a subject wears at least one filter described herein, which helps 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 also 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 the subject's exposure to artificial light in the evening, preventing the subject's internal clock from determining that it is time to be awake. In addition, the subject can adjust the subject's light / dark cycle by increasing exposure to light before sunrise.

[0033]

[0061] Furthermore, it has recently been clinically demonstrated that wavelengths around 620 nm also contribute to photophobia in certain individuals. Similarly, benefits may be achieved by preferentially attenuating light containing wavelengths around 620 nm, although the exact pathways for the neurological effects are not yet fully understood.

[0034]

[0062] Melanopsin includes bistable isoforms, each of which exhibits a unique absorption spectrum. The isoforms can be active and inactive isoforms. The active isoforms can be physiologically active. The inactive isoforms can be physiologically inactive. The absorption of light based on the absorption spectrum of each isoform can result in isomerization of melanopsin. Benefits can be achieved by impeding, limiting, or preventing isomerization of melanopsin by attenuating light at or about 590 nm.

[0035]

[0063] FL-41 lens tints are sometimes applied to migraine sufferers. FL-41 tints block (by absorption) a broad range of wavelengths. These wavelengths include those associated with melanopsin absorption. FL-41 dyes can be infiltrated into certain types of plastic eyeglass lenses. The amount of dye infiltrated determines the degree of light intensity that is blocked overall. "FL-41 35" tints are effective for many patients in indoor environments. However, if the light source increases in intensity, for example, by moving to an outdoor environment, "FL-41 35" may not be as effective.

[0036]

[0064] FIG. 2 shows the measured transmission spectrum of "FL-41 35". FIG. 2 further shows 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" staining blocks or attenuates about 55% of the light that would otherwise be absorbed by melanopsin ganglion cells. Additionally, as shown in FIG. 3, the FL-41 staining blocks a large portion of the visible spectrum that is not associated with melanopsin, attenuating by about 47% across the visual response spectrum. Further blocking the visible response spectrum may be detrimental. For example, blocking the visible response spectrum may adversely affect normal vision. In other instances, blocking the visible response spectrum may produce an undesirable color scheme that may be distracting or less desirable to the wearer.

[0037]

[0065] In bright light situations, such as outdoor environments, tints with greater levels of spectral attenuation may be used, such as "FL-41 55." The transmission spectrum of this filter and its effect on the action potential spectrum are shown in FIG. 4 (over the "effective action potential spectrum" of melanopsin) and FIG. 5 (over the visible light spectrum). This filter attenuates about 89% of the light that would otherwise be absorbed by the melanopsin cells, but also attenuates about 81% of the visual response spectrum. This additional spectral attenuation may further impair vision in low light levels or other situations.

[0038]

[0066] Overall, general drawbacks of FL-41 include its rose-tinted appearance, color vision distortion, limited applicability (i.e., it may only be applicable to certain plastics and not to glass lenses, computer screens, windows, car windshields, lighting substrates, light bulbs, or other optical elements), and low quality control over the coloring process (due in part to variability in the hard coating layer that can be colored). Although FL-41 may be effective in certain applications, it is not designed to down-regulate 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]

[0067] 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 about 480 nm, the long-pass filter may transmit more wavelengths longer than about 500 nm or 520 nm, while attenuating light at wavelengths shorter than about 500 nm or 520 nm.Similarly, to adjust the exposure of cells in human eyes to wavelengths of about 620 nm, the short-pass filter may transmit more wavelengths shorter than about 600 nm or 580 nm, while attenuating light at wavelengths longer than about 600 nm or 580 nm.

[0040]

[0068] Other examples of more desirable optical filters may 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 remainder of the light spectrum in its entirety, such that the spectral transmittance response of the filter takes the form of a notch. For melanopsin, the center location of the notch may be close to the absorption maximum wavelength of the melanopsin transduction pathway (approximately 480 nm), although other locations may 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 contemplated.

[0041]

[0069] Other optical filter techniques such as pigmentation including dye mixtures, 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 may be used to form filters in accordance with the present disclosure. Nanoparticle coatings that may be used in optical filters in accordance with the present disclosure include metal nanoparticles (e.g., Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g., TiO 2 , Ta 2 O 5 The nanoparticles may include nanoparticles such as nanoparticles of different sizes, such as nanoparticles of different sizes, 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 shapes of these particles may be spherical, ellipsoidal, other shapes, or combinations thereof. The host materials may include polymers, sol-gels, other host materials, or combinations thereof. The extinction spectra of these nanoparticles may be calculated using Mie scattering theory or its derivatives.

[0042]

[0070] One embodiment of the multi-layer filter 600 shown in FIG. 6 includes a substrate 602, a first layer 604, and a second layer 606. As shown, the first layer 604 may include a high refractive index material, and the second layer 606 may include a low refractive index material. In other embodiments, the first layer 604 may include a low refractive index material, and the second layer may include a high refractive index material. Additionally, the first layer 604 is shown adjacent to the substrate 602. In other embodiments, the first layer 604 may 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 may use any substrate described herein. For example, the substrate 602 may include a color layer (not shown) on the same side and / or opposite side of the first layer 604 and the second layer 606 (i.e., the front and / or rear side of the substrate). In other examples, the substrate 602 itself may be impregnated with color. Exemplary coloring techniques and amounts of coloring are described below. Other embodiment multi-layer filters are further described herein.

[0043]

[0071] 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, a variety of substrates, colors, other features, or combinations thereof may be used with the nanoparticle filter 700. Other embodiment nanoparticle filters are described herein.

[0044]

[0072] Other types of filters that may 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]

[0073] In addition to these various filter types, further considerations may include the impact of the designed filter on the visual response spectrum, as determined by the photoreaction of rods and cones. One consideration may include minimizing spectral distortion. Consideration may be given to adding additional or other constraints to the filter design, including optimization methods such as considering angular sensitivity, which may be compensated for, for example, by designing the center of the notch to be slightly red-shifted from about 480 nm when attenuating light near 480 nm toward melanopsin ganglion cells, by using multi-layer dielectrics, to account for the blue-shift of the filter response that occurs for off-axis illumination. Depending on the wavelength being attenuated, the degree of red-shift or blue-shift may vary. Optimization may further include broadening the spectral width of the filter 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 combining filters with some form of tinting.

[0046]

[0074] Described herein is one embodiment of a method for producing 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 FIG. 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]

[0075] 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]

[0076] The effect of an optical filter such as the 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]

[0077] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0050]

[0078] A figure of merit (FOM) may also be defined that compares the masking of the melanopsin response to the masking of the visual response spectrum.

number

[0051]

[0079] FIG. 8 illustrates an embodiment of a method 800 for designing an optical filter that prevents light absorption by melanopsin cells, which 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]

[0080] Many embodiments described herein use multi-layer 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 respect, the optical filter design embodiments of the present disclosure assume a typical transparent substrate such as a spectacle lens with a refractive index of about 1.5 and an anti-reflective coating added to the back surface (i.e., the surface closest to the user's eye). Other substrates with other refractive indices and with or without a back anti-reflective coating are therefore contemplated. Minor modifications in the filter design may be necessary to compensate for different substrate materials and / or different coatings on those substrates. Further considerations may need to be addressed, such as the compatibility of various thin film materials with various substrate materials, which may require further design optimization, and the curvature of the lens substrate. The substrate may include an adhesion layer (e.g., a thin layer of chrome) between the substrate or a layer on the substrate and any additional coatings.

[0053]

[0081] There are numerous design approaches to multilayer long-pass 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 take into account many constraints during optimization to reduce the likelihood that any two filter designs will be identical, even if they achieve the same light blocking properties or produce the same physiological results. Only a few examples appear herein, and are not intended to be limiting in any way. Other approaches may be taken to achieve similar results, as well as further optimizations may be performed in accordance with the present disclosure to provide more ideal properties or to provide similar properties with fewer layers.

[0054]

[0082] In addition, multilayer coatings and other coatings may be applied to the tinted lens or substrate. There are several reasons why this combination may be desirable. One reason may include that the spectral characteristics of the tint may relax design constraints on thin film filters. For example, combining a FL-41 "basic 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 take into account the spectral variation of 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 the local tilt of the tint spectral response. Another reason for using a basic tint may be to reduce any undesired 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 color scheme of its own.

[0055]

[0083] For example, in one embodiment of a filter designed to block 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 of the blocked wavelengths) may be reflected back to the user's eye. In other words, light that is blocked from the front (by reflection in the case of a multi-layer filter) may then be reflected from the back side. This may not be a concern if there is primarily a single light source in front of the subject. However, if, for example, a very bright light is observed or there are multiple light sources, this back reflection may be harmful to the user.

[0056]

[0084] An exemplary approach to creating a longpass or notch filter involves using alternating layers of high and low index materials. An exemplary low index dielectric material is MgF 2 and SiO 2 Generally, MgF 2 are used in single and multi-layer anti-reflective coatings. Exemplary high refractive index materials are TiO 2 , Ti 3 O 5 , ZrO 2 , and Ta 2 O 5 Metal oxides such as Si 3 N 4 Many other suitable materials, including polymer layers, may be used.

[0057]

[0085] Optical filters that attenuate light around various wavelengths, such as 480 nm, 620 nm, or other specific wavelengths, may follow a similar design. An embodiment optical filter design and the effect of the filter on the spectrum of light illuminating the melanopsin cells that generate effective (and attenuated) action potentials are shown in Figures 9 and 10. This design is similar to the FL-41 filter in that 55% of the light absorbed by the melanopsin cells is blocked or attenuated. The design is targeted to be as clinically effective as the FL-35 coating, and should provide the same relief of migraine (or photosensitivity) symptoms as the FL-41 coating, with only an 18% attenuation across the visual response, and with significantly less visual distortion. In this embodiment, the low refractive index material is SiO 2 and the high refractive index material is TiO 2 and MgF 2 is used as the outermost layer, for a total of 11 layers. Exemplary layers and materials are: outermost layer (MgF 2 ) to the innermost layer (165 nm thick TiO 2 ) are listed in the following table. This filter has an FOM of ≈ 3. [Table 1]

[0058]

[0086] The spectral location of the center of the notch filter may be determined by the thickness of each layer of the notch filter. However, many embodiments herein assume that the spectral location of the notch is about 480 nm, although other spectral locations are contemplated. For example, as more information regarding the action potential spectrum of the melanopsin pathway becomes known, the spectral location may be shifted, for example, to 620 nm, according to the new information. Alternatively, in other examples, the spectral location may be positioned to achieve a particular result, for example, to attenuate wavelengths other than those of the action potential spectrum of the melanopsin pathway.

[0059]

[0087] The width of the notch can be determined by the difference in the refractive index of the different layers. The depth of the notch can be determined by the number of layers. The transmission outside the notch area can be increased and flattened by including additional layers, and may also include a single or multi-layer anti-reflective coating added to the rear surface of the lens to reduce rear reflections. Further design optimization can be used to increase the depth of the notch, which can further suppress the excitation of melanopsin cells, 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]

[0088] Greater attenuation of the effective melanopsin action potential spectrum can be achieved by either deepening or widening the filter notch, 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, and 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]

[0089] Various designs can achieve significant attenuation across the melanopsin action potential spectrum. Figures 13 and 14 show an embodiment notch filter that has an FOM value of about 3 and uses 19 dielectric layers to provide attenuation of melanopsin action potentials similar to the FL-41 55 filter, which blocks about 89% of the light but only blocks about 29% of the visual response spectrum. The design of the gyro is shown in Fig. 1. Exemplary layers and materials are shown in Fig. 1. The outermost layer (MgF 2 ) to the innermost layer adjacent to the substrate (TiO with a thickness of 160.3 nm). 2 ) are listed in the following table. [Table 2]

[0062]

[0090] 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, for example to minimize or reduce the effect of the angle of incidence.

[0063]

[0091] 15 shows a 10 layer filter design in one embodiment with a notch centered at 485 nm for normal incidence light. At normal incidence, the filter of this embodiment blocks approximately 61% of the amount of light for the melanopsin spectrum and attenuates only approximately 21% of the light for the visual response spectrum, resulting in an FOM value of approximately 2.9.

[0064]

[0092] Figure 16 shows the effect of the filter of the embodiment shown in Figure 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]

[0093] The filter of this embodiment has an outermost layer (MgF 2 ) to the innermost layer (127 nm thick TiO 2 ) have the layer properties described below and listed in the following table. [Table 3]

[0066]

[0094] In the filter of the embodiment described with reference to FIGS. 8 to 15, low refractive index MgF 2layers were used. Other embodiments may not require this material. For example, FIG. 17 shows a filter design for one embodiment that blocks approximately 73% of the melanopsin action potential spectrum (or light amount) and approximately 21% of the light amount of the visible response, with an FOM value of approximately 3.5. The layer properties of the filter design shown in FIG. 17 are listed in the following table, from outermost to innermost layer. [Table 4]

[0067]

[0095] As previously mentioned, 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 accomplished with another embodiment of the filter design, where 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 an anti-reflective coating (with T≈1) is assumed to be applied to the rear surface of the substrate.

[0068]

[0096] 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]

[0097] At any particular wavelength, the ratio of transmitted to reflected light can be set by the transmittance of the thin film coating and the tint. For example, if a transmittance of about 20% is desired at a desired wavelength (about 480 nm in this example), then only a specific combination of thin film transmittance and tint transmittance can be used. Furthermore, if a reflection of about 10% is desired, then only one combination of thin film transmittance and tint transmittance is allowed. These relationships can be described as follows:

number

number

[0070]

[0098] The amount of light D received by a melanopsin cell due to back-reflected light into a user's eye can be expressed similarly to the amount of light received by a melanopsin cell 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 FIG. 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]

[0099] The normalized amount of light received by a melanopsin cell due to back-reflected light can be calculated by the following formula:

number

[0072]

[0100] Similar and normalized light quantities are calculated in relation to the visual response spectrum. obtain. D R-vis=∫L(λ)R(λ)V(λ)dλ (10)

number

[0073]

[0101] The amount of back-reflected light relative to the action potential spectrum of the melanopsin pathway is expressed 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 coloration 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 the melanopsin cells and the normalized amount of back-reflected light can reduce the symptoms suffered by photophobic users.

[0074]

[0102] The following table, for example, lists specific transmittances and back reflectances at about 480 nm: 10 shows additional embodiment filter designs using several possible notch and tint transmission combinations that result in a filter having a wavelength of 100 nm and a wavelength of 150 nm. Note that due to the notch response, the transmission of light outside the notch will be greater than the transmission of light within the notch, resulting in an amount of back-reflected light that is less than that occurring at the center of the notch. However, while these examples are specific to a notch centered near 480 nm, other wavelengths may be selected as described herein.

[0075]

[0103] Table 1 provides examples of different transmissions through the front side while maintaining a fixed 10% back reflectance at a particular wavelength (e.g., about 480 nm) or wavelength range. This value of back 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 reflectance may be desirable. [Table 5]

[0076]

[0104] Table 2 provides another embodiment in which greater backside reflectance is permitted. These designs may be more appropriate for "wrap" style eyeglass frames or sports frames that prevent light from entering the eye other than that passing through the front of the lens. [Table 6]

[0077]

[0105] Other embodiment filters may be used to adjust the transparency of the notch to provide a given back 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]

[0106] The R values ​​described herein can be used to determine the maximum amount of back reflected light. For example, an R value of about 0.10 may be used as the amount of desired back-reflected light weighted across the action potential spectrum of the melanopsin pathway, the visual spectrum, or both. The R value is based on the desired wavelength to be attenuated, so that light of other wavelengths may be attenuated based on filters designed to achieve an R value equal to or less than that according to the table above. For example, for a wavelength of about 480 nm, which has an R value of about 0.10, wavelengths of about 470 nm or 490 nm may be attenuated based on filters designed to achieve an R value equal to or less than that according to the table above. The R value at 0 nm may be less than 0.10, for example about 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 ​​may also be expressed as percentages.

[0079]

[0107] 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 contemplated and may be suitable for different levels of photosensitivity of the user, 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]

[0108] Manufacturing considerations may also be taken into account when implementing a filter design. Typically, deposition of materials is achieved using sputtering, evaporation, or chemical vapor deposition techniques. Deposition conditions can be optimized to minimize stress in the thin film material. Often, high temperature thermal annealing can be performed after deposition to relieve stress in the deposited material, but annealing is often not applicable to plastic lenses. Since eyeglass lenses represent curved substrates, it can be difficult to achieve a constant film thickness during deposition. To achieve a constant film thickness, target and source positional changes 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]

[0109] The following examples describe optical filter designs that were tested and their results. The notch coating was produced on a polycarbonate or CR-39 plano lens with an anti-scratch coating. A thin layer of Cr was deposited on the substrate to act as an adhesion layer in the thin film stack. The transmission spectrum through an exemplary coated lens is shown in FIG. 18A. The notch is centered at about 482.9 nm, has a width of about 55.5 nm, and has a minimum transmission of about 24.5%. The filter of this embodiment blocks about 58% of the melanopsin action potential spectrum and blocks about 23% across the visible spectrum, with an FOM value of about 2.6. In contrast, FIG. 18B shows the transmission spectrum of the coated lens using a 620 nm notch filter.

[0082]

[0110] 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. To participate in the study, all participants complained of chronic headaches, defined as headaches on more than 15 days per month. A formal questionnaire, the HIT6, was used to assess the impact of headaches on the 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 the participants' quality of life. [Table 8]

[0083]

[0111] In another embodiment, a thin notch coating is applied to an FL-41 tinted lens. The transmission and back reflection spectra are shown in Figures 19 and 20. Various levels of FL-41 tinting were added to a tintable scratch-resistant layer (also called a hard coat) on polycarbonate or CR-39 lenses. A multi-layer notch filter was then added to the front of each lens, and a conventional anti-reflection coating was added to the rear of each lens. As can be seen in Figures 19 and 20, the FL-41 tinting significantly reduced the back reflection. However, in transmission, 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 with a slightly blue-shifted notch design.

[0084]

[0112] The following table shows the levels of obscuration across the melanopsin spectrum and the visual response spectrum. The following table lists the FOM values ​​for each stain level and the results for each stain level. Similar results can be expected using other stains, such as gray stains, such as BPI's "sun gray." [Table 9]

[0085]

[0113] The coatings described herein may also be combined with other techniques. For example, A filter coating may be added to a tinted lens, photochromic materials may be incorporated, polarizing 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]

[0114] FIG. 21. Producing an optical filter that reduces the frequency and / or severity of photophobia 2 illustrates an exemplary embodiment of a method 2100 for designing a filter of at least one embodiment described herein. The 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, for situations such as indoor fluorescent lighting and / or computer screens in an office, retail, or home environment, or outdoor lighting such as sunlight due to normal outdoor or sporting activities. As shown in step 2104, an amount of light received by melanopsin cells may be determined (e.g., using Equation (1)). As shown in step 2106, an amount of light received across a visual response spectrum may be determined (e.g., using Equation (2)). As shown in step 2108, an optical filter may be designed and manufactured 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. 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 of the entire visual response spectrum may be used.

[0087]

[0115] FIG. 22 shows a method for reducing the frequency and / or severity of photophobia or circadian rhythm 2 shows an exemplary embodiment of a method 2200 for adjusting a visual response spectrum. The method 2200 may be used in connection with at least one embodiment of a filter described herein. The 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 the 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, the first amount of light and the second amount of light may be used to fabricate an optical filter. The first amount of light and the second amount of light 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 reduced or separated. For example, a range greater than or less than the entire visual response spectrum may be used.

[0088]

[0116] In addition to adjusting the exposure of melanopsin ganglion cells to light around 480 nm, Clinical trials have demonstrated that attenuation of light at a wavelength of about 620 nm may also provide improvement in reducing symptoms associated with photosensitivity. Although light at a wavelength of about 620 nm is not believed to affect melanopsin ganglion cells, it has been demonstrated that attenuation of light at about 620 nm 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 provide benefits in some individuals in the treatment of blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy.

[0089]

[0117] 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]

[0118] Additionally, filters 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 preferentially filters wavelengths of light from about 450 nm to about 510 nm and from about 580 nm to about 640 nm. In yet other embodiments, the filter may attenuate light between about 470 and about 490 and between about 610 nm and about 630 nm.

[0091]

[0119] Optical filters are manufactured according to the processes and using the materials described above. 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 host material, 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 include using alternating layers of high and low refractive index materials. An exemplary low refractive index dielectric material is MgF 2 and SiO 2 Exemplary high refractive index materials include TiO 2 , Ti 3 O 5 , ZrO 2 , and Ta 2 O 5 and other metal oxides, as well as Si 3 N 4 Many other suitable materials, including polymer layers, may be used.

[0092]

[0120] 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 may 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 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]

[0121] Similar light quantities 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]

[0122] The effect of an optical filter such as a nanoparticle notch filter can be expressed as follows: , by taking the ratio of the amount of light calculated with the filter to the amount of light without the filter, thus reducing the amount of light as explained.

number

[0095]

[0123] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0096]

[0124] FOM comparing light obscuration at approximately 620 nm with obscuration of the visual response spectrum can also be defined.

number

[0097]

[0125] Optical filters are described for the attenuation of light to which melanopsin cells are sensitive. The optical filters may include multilayer dielectric films similar to those described above, or may include nanoparticle-based optical filters, color filters, tints, resonant guided mode filters, rugate filters, or any combination thereof. Nanoparticle-based optical notch filters may include nanoparticles dispersed on the surface of a host material or embedded in the host material. Thus, such filters may be used in a substantially transparent host material, such as a lens material for eyeglasses, or may simply be added to the surface. For example, the filters may be placed on the surface of eyeglass lenses to attenuate light approaching the user's eye. In other applications, the filters may be placed directly on a light source, e.g., an electronic display device such as a computer screen, or on a light source such as a light bulb or window.

[0098]

[0126] The attenuation of light by nanoparticle-based notch filters depends on the shape of the nanoparticles and the host material. The amount or density of nanoparticles on or embedded within the host material, the composition of the nanoparticles, the size of the nanoparticles, and the refractive index of the host material can be tailored. Thus, the attenuation spectrum of a nanoparticle-based optical notch filter can be tailored to a particular curve by selecting materials and profiles that result in the centering of the curve at a desired wavelength, maximum attenuation at a desired wavelength value, and producing an attenuation curve with an appropriate shape and full width at half maximum.

[0099]

[0127] For example, increasing the refractive index of the nanoparticle matrix increases the refractive index of the solid particles and the core-shell Using longer particle sizes, including ZnO particles, and / or other metals may shift the attenuation spectrum towards longer wavelengths. The attenuation spectrum changes because attenuation 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. Thus, when the refractive index of the host material is increased, not only does the attenuation spectrum red-shift, but the amount of scattering and, therefore, the attenuation of light increases as well.

[0100]

[0128] 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. Thus, the relative refractive index can also be altered by changing the composition of the nanoparticle. The nanoparticles can be solid, consisting of a single material, or a core-shell configuration, with a core of a first material and a shell of a second material. In either case, the material can be a single element, a compound, or an alloy. As mentioned above, nanoparticles can be metal nanoparticles (e.g., Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g., TiO 2 , Ta 2 O 5etc.), 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. For example, increasing the proportion of Ag in an Ag / Al alloy solid nanoparticle can both increase the amplitude and red-shift the extinction curve for that nanoparticle.

[0101]

[0129] In addition, the nanoparticles used may be circular, elliptical, rectangular, hexagonal, octagonal, or The cross-sections may include other polygonal shapes. Spherical particles have the most distinct spectra, since they have a single narrow main peak that allows for optimization using size and compositional variations. However, it is possible to use a combination of particles of other shapes to create a desired filter spectrum. For example, the extinction spectrum of a 40 nm spherical nanoparticle filter can be broadened by simply introducing cubic or octahedral nanoparticles of comparable dimensions.

[0102]

[0130] In contrast, the extinction curves of core-shell nanoparticles vary with the relative thickness of the core and shell. For example, SiO 2 Reducing the thickness of the Ag shell relative to the dimensions of the 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 includes spherical core-shell nanoparticles. In another embodiment, the spherical core-shell nanoparticles include an Ag shell and a Si core. In yet another embodiment, the spherical Ag / Si core-shell nanoparticles include an Ag shell with a radial thickness of 45 nm and a Si core with a radius of 15 nm.

[0103]

[0131] FIG. 23 illustrates a filter used in conjunction with multi-layer thin film filters to form a composite filter 2300. 23 shows a nanoparticle-based optical filter that is configured to filter 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 may enter a filter that includes nanoparticles 2304 that may be disposed on or embedded within a matrix 2306 disposed on a surface of a thin film 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 that enters the matrix 2306 with the nanoparticles 2304 embedded therein may be sunlight. The attenuated light 2310 that enters the thin film filter 2308 may include an amount of light that is reduced in the range attenuated by the nanoparticles 2304. The filtered light 2312 that exits 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.

[0104]

[0132] FIG. 24 illustrates a composite optical filter that reduces the frequency and / or severity of photophobia. 2 illustrates an embodiment of a method 2400 for manufacturing, which 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 due to normal outdoor or sporting activities.

[0105]

[0133] As shown in step 2404, a first amount of light received by the subject is determined (e.g., according to the formula As shown in step 2406, a second amount of light received by the human eye at a wavelength of about 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. 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), as described herein. In other embodiments, amounts of light 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.

[0106]

[0134] FIG. 25 shows a method for reducing the frequency and / or severity of photophobia or altering the circadian rhythm. 25 shows an embodiment of a method 2500 for using a composite filter that adjusts. The method 2500 may be used in conjunction with at least one embodiment of the composite filter described herein. The 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 that is preferentially attenuated across the action potential spectrum of the melanopsin cells may be transmitted. As shown in step 2506, a second amount of light that is 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.

[0107]

[0135] A study demonstrating the benefits of attenuating light near about 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 was a notch filter at 480 nm. The other coating was a notch filter at 620 nm. Typical transmission spectra of gray tinted lenses with the various coatings used in the study are shown in Figures 23A and 23B. The 480 nm notch filter shown blocks approximately 68% of the light absorption by melanopsin and blocks 42% of visible light. The 620 nm notch filter shown blocks approximately 66% of the 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 provides 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 provide an average of 67±2% blocking at approximately 620 nm and an average of 43±4% visible blocking. Neither the subjects nor the clinical coordinator 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, which means that they had at least 15 headache days per month. Those with at least 15 headache days per month are considered to be migraine sufferers with the most severe symptoms.

[0108]

[0136] To assess the effectiveness of the intervention, the primary outcome measure was a six-question questionnaire. The Headache Impact Test (HIT-6), which is a 6-question instrument designed and validated to assess the impact of headaches on a person's life, was selected. The HIT-6 is a 6-question instrument designed and validated to assess the impact of headaches on a person's life. Scores are continuous variables 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.

[0109]

[0137] The subjects first underwent a four-week "preclearance" period during which they did not wear the test lenses. The period served to establish baseline characteristics of the subjects' headaches. Subjects were first randomized using block randomization as to which lenses they would wear. Subjects were instructed to wear the glasses all day for two weeks. Subjects then underwent a two-week "clean-up" period during which the test lenses were not worn. Subjects then underwent a further two-week "clean-up" period during which the test lenses were not worn. Finally, the subjects underwent a final "post-clearance" period during which no test lenses were worn, which determined the "end point" of exit for the headache profile.

[0110]

[0138] There is a great deal of variability in the frequency and severity of headaches. This variability can occur even within the same patient. Due to variability, "pre-cleaning" and "post-cleaning" periods were added. These additional periods during which the test lenses were not worn minimized the effect of "baseline variation" among study subjects.

[0111]

[0139] The HIT-6 questionnaire was administered before and after each period of the study. Six questionnaires were administered to each surgeon. The study initially enrolled 48 participants, with 37 completing the 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. According to the interpretation of the HIT-6, these 33 subjects suffered from headaches that "very severely affected" their lives. Both the 480nm and 620nm filter lenses showed a statistically significant reduction in HIT-6 values.

[0112]

[0140] Of the 37 participants who completed the study, 9 subjects were wearing the 480 nm lens. 480 nm lenses, 5 subjects were able to exit the HIT-6 category of "very severely affected" while wearing 480 nm lenses, 5 subjects were able to exit this category while wearing 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 in the HIT-6 while wearing 480 nm lenses, 10 subjects experienced at least a 6 point improvement in the HIT-6 while wearing 620 nm lenses, and 3 subjects experienced at least a 6 point improvement in the HIT-6 while wearing either of these lenses. This analysis shows that wearing either 480 nm or 620 nm spectacle lenses resulted in a statistically significant reduction in the HIT-6. However, there was no substantial difference when comparing the effect of 480 nm lenses to 620 nm lenses (p=0.195).

[0113]

[0141] 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 they needed abortive medication, behaved similarly to the primary outcomes for either the 480 nm or 620 nm spectacle lenses: subjects experienced significant reductions in these parameters wearing either the 480 nm or 620 nm lenses. In all three cases, there was no substantial difference in the effect of the 480 nm lenses compared to the 620 nm lenses.

[0114]

[0142] Melanopsin in melanopsin ganglion cells is a bistable pigment. can be isomerized during exposure to light of a particular wavelength. FIG. 27 is a graph 2700 that illustrates a schematic of 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.

[0115]

[0143] The second isoform may exhibit a second absorption spectrum 2706. The absorption spectrum 2706 may absorb 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.

[0116]

[0144] Figure 28 shows the active absorption spectrum 2802 and the inactive absorption spectrum 2803 of melanopsin. 28 shows a graph 2800 of an active absorption spectrum 2802 and an inactive absorption spectrum 2804 corresponding to an active isoform of melanopsin and an 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 about 484 nm. The inactive absorption spectrum 2804 may have a maximum at about 587 nm.

[0117]

[0145] The inactive isoform of melanopsin follows the inactive absorption spectrum2804. The inactive isoform of melanopsin can absorb wavelengths of light that are different from the inactive isoform. The light absorbed by the inactive isoform of melanopsin can contribute to the conversion of the inactive isoform to the active form of melanopsin. The active form of melanopsin can contribute to the photophobia response in humans. In at least one embodiment, the attenuation of the light absorbed by the inactive isoform interferes with the isomerization of melanopsin and can reduce the symptoms of photosensitivity in some people, such as pain or discomfort in response to light, and the frequency and / or severity of migraines and other headaches, and can also be effective in treating blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy in some people.

[0118]

[0146] of 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 about 590 nm may attenuate light absorbed by the inactive isoform of melanopsin.

[0119]

[0147] In one embodiment, light between about 560 nm and about 620 nm is attenuated. In another embodiment, an improvement may be realized by attenuating light between about 570 nm and about 610 nm. In yet another embodiment, an improvement 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.

[0120]

[0148] Additionally, filters may attenuate wavelengths of light in multiple ranges. For example, In one embodiment, the filter can attenuate light absorbed by inactive isoforms of melanopsin and light absorbed by active isoforms of melanopsin. In one embodiment, the filter can attenuate light at about 590 nm in addition to attenuating light at about 480 nm. In another embodiment, the filter can preferentially attenuate wavelengths of light from about 450 nm to about 510 nm and from about 560 nm to about 620 nm. In yet another embodiment, the filter can attenuate light between about 470 and about 490 and between about 580 nm and about 600 nm.

[0121]

[0149] Similar to the 480nm and 620nm filters mentioned above, this filter also filters out 590nm light. The optical filters that can be attenuated may include high-pass filters, low-pass filters, optical notch filters, or combinations thereof. The optical notch filters may include multiple layers of dielectric materials, nanoparticles dispersed or embedded in a host material, 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 include using alternating layers of high and low refractive index materials. An exemplary low refractive index dielectric material is MgF 2 and SiO 2 Exemplary high refractive index materials include TiO 2 , Ti 3 O 5 , ZrO 2 , and Ta 2 O 5and other metal oxides, as well as Si 3 N 4 Many other suitable materials, including polymer layers, may be used.

[0122]

[0150] It attenuates the wavelengths absorbed by the active isoform of melanopsin mentioned above. As with the embodiment intended to be used in the present invention, an optical filter designed to attenuate wavelengths around 590 nm can be manufactured 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 may 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 may be performed for any light source with a known spectrum.

[0123]

[0151] 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.

[0124]

[0152] 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

[0125]

[0153] The "attenuation" of the amount of light can be expressed, for example, as follows:

number

[0126]

[0154] FOM comparing light obscuration at approximately 590 nm with obscuration of the visual response spectrum can also be defined as follows:

number

[0127]

[0155] FIG. 29 illustrates a method 2900 for reducing symptoms associated with photophobia. 29.00 includes a step 2902 of receiving light, a step 2904 of attenuating a first wavelength, and, optionally, a step 2906 of attenuating a second wavelength. The attenuation of the first wavelength may then disrupt the bistable pigment cycling (step 2908), which will be described with reference to FIG. 27. In one embodiment, the first wavelength may be determined by a maximum of the active or inactive absorption spectrum of the bistable pigment. In another embodiment, the first wavelength may be determined by a maximum of the active absorption spectrum 2802 or the inactive absorption spectrum 2804 of melanopsin, which will be described with reference to FIG. 28. In yet another embodiment, the first wavelength may be 480 nm. In another embodiment, the first wavelength may be 590 nm.

[0128]

[0156] Attenuating a wavelength means that that wavelength or should be understood to mean preferentially attenuating a range that includes that wavelength. For example, attenuating the 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 the 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.

[0129]

[0157] Attenuating the second wavelength 2906 results in 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 of the active or inactive absorption spectrum of the bistable dye. In another embodiment, the first wavelength may be determined by a maximum of the active absorption spectrum 2802 of melanopsin or a maximum of 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.

[0130]

[0158] Attenuating the first wavelength 2904 and, optionally, attenuating the second wavelength 2906 Attenuating the first wavelength 2904 may disrupt bistable dye cycling. Attenuating the first wavelength 2904 may inhibit isomerization of the bistable dye from a first isoform to a second isoform. The first isoform may be an active or inactive isoform. Attenuating the second wavelength 2906 may inhibit isomerization of the bistable dye from the second isoform back to the first isoform.

[0131]

[0159] 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 processes described above to provide a low pass filter, high pass filter, or optical notch filter that preferentially attenuates 590 nm light. The filter may include multi-layer dielectrics, nanoparticle embedded coatings, color filters, tints, resonant guided mode filters, rugate filters, and any combination thereof. The filter may further include nanoparticle embedded 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.

[0132]

[0160] As used herein, the terms "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 in the range of less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the stated amount.

[0133]

[0161] Although the present invention is described in relation to the above embodiments, it should be noted that these descriptions are not intended to limit the scope of the present invention to the specific forms described, but rather, these descriptions are intended to cover alternatives, modifications, and equivalents that may fall within the scope of the present invention. Any component of the above embodiments may be combined with any other component of the above embodiments. For example, any manufacturing method or light attenuation method described above may be combined with the optical filter and associated wavelengths described. Thus, the scope of the present invention fully encompasses other embodiments that may be 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 or regulating circadian cycles by controlling exposure of cells in a human eye to light having a wavelength of about 590 nm, comprising: an optical filter configured to transmit less than a first amount of light at a wavelength of about 590 nm and to transmit more than a second amount of light weighted across the visual spectral response; An apparatus comprising: [Form 2] the first amount of light is substantially all of the light at the wavelength of about 590 nm; the second amount of light being substantially all of the light outside the wavelength of about 590 nm, weighted across the visual response spectrum; 2. The apparatus according to claim 1. [Form 3] the first amount of light being substantially all of the light above a short pass filter wavelength between about 560 nm and 620 nm; the second amount of light being all light across the visual spectral response including wavelengths less than the short pass filter wavelength. 2. The apparatus according to claim 1. [Form 4] the second amount of light includes a third amount of light having a wavelength less than about 590 nm or greater than about 590 nm; 2. The apparatus according to claim 1. [Form 5] the second amount of light includes a third amount of light having a wavelength less than about 590 nm and a fourth amount of light having a wavelength greater than about 590 nm. 2. The apparatus according to claim 1. [Form 6] The first amount of light is the amount of light at about 590 nm received by a recipient cell of the subject (D rec,590 ) and The second amount of light is the amount of light received across the visual response spectrum (D vis ) and A ratio including the first amount of light and the second amount of light is defined as a figure of merit (FOM); The figure of merit is

number

Claims

1. 1. An apparatus for reducing the frequency and / or magnitude of photophobia or modulating circadian cycles by controlling exposure of melanopsin ganglion cells in the retina to light, the apparatus comprising: a composite optical filter, the composite optical filter comprising: The response spectrum R 590 (λ) at a wavelength of 590 nm is a Gaussian function having a central wavelength of 590 nm and a full width at half maximum of 50 nm, and the amount of light obtained by integrating the light spectrum L(λ) weighted by the spectral transmittance T(λ) of the optical filter with respect to wavelength is the amount of light (D) of filtered light at a wavelength of 590 nm received by the melanopsin ganglion cells of the subject. ｒｅｃ，５９０ ) and The amount of light D rec,590 (T=1) of light at a wavelength of 590 nm received by the subject's melanopsin ganglion cells in the absence of an optical filter is calculated by integrating the light spectrum L(λ) with respect to wavelength, weighted by the response spectrum R 590 (λ) at a wavelength of 590 nm, which is a Gaussian function having a central wavelength of 590 nm and a full width at half maximum of 50 nm; the response spectrum R 480 (λ) at a wavelength of 480 nm, which is a Gaussian function having a central wavelength of 480 nm and a full width at half maximum of 52 nm, and the light amount D rec,480 obtained by integrating the light spectrum L(λ) weighted by the spectral transmittance T(λ) of the optical filter over wavelength, is the amount of light of filtered light at a wavelength of 480 nm received by the melanopsin ganglion cells of the subject; The amount of light D rec,480 (T=1) of light at a wavelength of 480 nm received by the subject's melanopsin ganglion cells in the absence of an optical filter is calculated by integrating the light spectrum L(λ) with respect to wavelength, weighted by the response spectrum R 480 (λ) at a wavelength of 480 nm, which is a Gaussian function having a central wavelength of 480 nm and a full width at half maximum of 52 nm; The amount of light received across the filtered visual response spectrum (D) is calculated by integrating the light spectrum L(λ) over wavelength, weighted by the normalized visual response spectrum V(λ) and the spectral transmittance T(λ) of the optical filter. ｖｉｓ ) and The amount of light received across the visual response spectrum in the absence of an optical filter, Dvis(T=1), is the amount of light received by integrating the light spectrum L(λ) over wavelength, weighted by the normalized visual response spectrum V(λ); The ratio including the light amounts D rec,590 and D vis and the ratio including the light amounts D rec,480 and D vis are defined as figure of merit (FOM) FOM1 and FOM2 of the optical filter, respectively, as shown in the following formulas: FOM1=[1-D rec,590 / D rec,590 (T=1)] / [1-D vis / D vis (T=1)] FOM2=[1-D rec,480 / D rec,480 (T=1)] / [1-D vis / D vis (T=1)] is determined by said FOM1 is at least 1 and said FOM2 is at least 1; Device.

2. the optical filter comprises at least one of a multi-layer dielectric coating, a nanoparticle embedded coating, a color filter, a tint, a resonant guided mode filter, a rugate filter, or any combination thereof; 2. The apparatus of claim 1.

3. the nanoparticle embedded coating comprises at least one of a metal nanoparticle, a dielectric nanoparticle, a semiconductor nanoparticle, a quantum dot, a magnetic nanoparticle, or a core-shell particle having a core material in the core and a shell material acting as the shell; 3. The apparatus of claim 2.

4. the metal nanoparticles include at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles; The dielectric nanoparticles are TiO ２ , Ta ２ O ５ or other dielectric nanoparticles, 4. The apparatus of claim 3.

Images