KR20200053471A - Methods, systems, and apparatus for reducing the frequency and / or severity of a photopneumococcal response or regulating a circadian cycle - Google Patents

Abstract

The optical filter can reduce the frequency and / or severity of light hypersensitivity reactions or adjust the daily cycle by controlling light exposure to the cells of the human eye and the visible spectral response of the human eye at certain wavelengths, such as 480 nm and 590 nm. Optical filters interfere with the isomerization of melanopsin in the human eye, reducing the availability of active isoforms, while attenuation of weighted light across the active potential spectrum of active isotypes attenuates the photoconductive cascade, resulting in a light-sensitive response. Effect. Embodiments of the optical filter are described. In one embodiment, the optical filter can be configured to transmit less than a first amount of light at a particular wavelength, and transmit more than a second weighted amount of light over a visible spectral response. Methods of making and manufacturing optical filters are also described.

Description

Methods, systems and devices for reducing the frequency and / or severity of photosensitive reactions or adjusting the daily cycle

[Cross reference of related applications]

This application is filed on August 9, 2017, United States Patent Application No. 15 / entitled "Methods, Systems and Devices for Reducing the Frequency and / or Severity of Photosensitive Hypersensitivity or Adjusting the Daily Cycle" Claims priority to 673,264, the contents of which are incorporated herein by reference in their entirety.

Light hypersensitivity, or light sensitivity, refers to light side effects characterized by several neurological conditions. The present invention relates to managing the effect of light on a subject. More specifically, the present invention relates to methods, systems and devices for reducing the frequency and / or severity of photosensitive reactions or regulating the daily cycle.

The retina of the eye contains various photoreceptor cells. These photoreceptor cells include rod cells (involved in black and white and low light vision), cone cells (involved in daytime vision and color vision), and melanopsin ganglion cells.

Melanopsin ganglion cells are photosensitive. This photosensitivity can transmit pain through the brain's pain pathway. These pathways are described by Noseda et al. Neuromechanical mechanisms for exacerbation of headaches by neuroscience: February 2010; 13 (2): 239-45 PMID 20062053, which is incorporated herein by reference in its entirety. It has already been demonstrated that the use of sunglasses to control ambient light can be effective in the treatment of light sensitive neurological conditions, including migraine and benign blepharospasm. A description of these beneficial effects was given by Good et al., “Using sunglasses for childhood migraine” September 1991; 31 (8): 533-6 PMID 1960058 and Blackburn et al., “FL-41 Hue Improves Light Sensitivity and Functional Limit of Flicker Frequency in Patients with Benign Eyelid Convulsions” May 2009; 116 (5): 997-1001 PMID 19410958, which is incorporated herein by reference in its entirety. In addition to the pain pathway, melanopsin ganglion cells are also connected to the humeral nucleus, where they are involved in the rhythm of the day cycle. These connections were made by Hannibal J. "The role of PACAP-containing retinal ganglion cells at day cycle timing"; Int Rev Cytol. 2006; 251: 1-39. review. PubMed PMID: 16939776, which is incorporated herein by reference in its entirety.

All animals have a unique biological "clock" that synchronizes them with Earth's 24-hour light / dark cycle. This watch sets the internal rhythm of the medicine ("circa") day ("dian"). This phenomenon is called "Human Sleep and One-Day Rhythm" by California Chaser, Gooley JJ. Cold Spring Harb Symp Quant Biol. 2007; 72: 579-97. Reviews PubMed PMID: 18419318, the entire contents of which are incorporated herein by reference. However, to maintain optimal synchronization with the light / dark cycle, the body's internal clock must be reset daily. This is in California, Chaser, "The Effect of Light on Human Day Cycle Pacemakers", Ciba Found Symp. 1995; 183: 254-90; Discussion 290-302. review. PubMed PMID: 7656689 and Duffy JF, Wright KP Jr. "Coupling with the human daily cycle system by light", J Biol Rhythm. August 2005; 20 (4): 326-38. review. As described in PubMed PMID: 16077152, it occurs when light from the environment is absorbed by melanopsin ganglion cells and is signaled to the part of the brain that acts as the body's "master clock", the crosstalk nucleus, both The entirety of which is incorporated herein by reference.

Rhodopsin is a photosensitive molecule in the eye's rod and cone cells. Rhodopsin has two metastable isomers, including active and inactive states. Rhodopsin isomerizes to inactive isoforms upon exposure to light. The inactive isoform of rhodopsin can be recycled in the retinoid cycle. During the retinoid cycle, rhodopsin leaves the photoreceptor and enters the retinal pigment epithelium. After being recycled to the active isoform, rhodopsin returns to the photoreceptor. Melanopsin Melanopsin of ganglion cells are Mure LS, Cornut PL, Rieux C, Drouyer E, Denis P, Gronfier C, Cooper HM. Melanopsin bistable: Fly's eye technique in the human retina. PLoS One. June 24, 2009; 4 (6): e5991. It is believed to undergo a process similar to that described in PubMed PMID: 19551136, the entire contents of which are incorporated herein by reference.

Therefore, it would be desirable to manage the effect of light on the object. More specifically, it would be desirable to provide methods, systems and devices for reducing the frequency and / or severity of photosensitive reactions. It would also be desirable to provide methods, systems, and devices for regulating the daily cycle.

Since melanopsin ganglion cells are sensitive to light wavelengths around 480 nm and are associated with the human pain pathway, it would be desirable to manage the painful effects caused by certain types of light. For example, stimulation of melanopsin ganglion cells can affect the frequency and / or severity of photosensitive reactions, so reducing the direct light stimulation of these cells in some situations, or stimulation of these cells in others It can be advantageous to reduce the exposure to light that is not directly related. These photosensitivity reactions include photosensitivity associated with migraine, concussion or traumatic brain injury, photosensitive epilepsy, and photosensitivity associated with benign eyelid spasm. Melanopsin ganglion cells are also involved in the daily cycle. Accordingly, methods, systems, and apparatus are provided for reducing the frequency and / or severity of a photosensitive response and / or regulating the day cycle by controlling light exposure to melanopsin ganglion cells or other parts of the eye.

An embodiment of a device for reducing the frequency and / or severity of a light sensitive response or regulating the daily cycle is described. The device comprises an optical filter configured to transmit light of less than a first weighted amount across the absorption spectrum of the melanopsin bistable isoform, and transmit more than a second weighted amount of light across the visible spectrum response. Includes. As an example, the light spectrum associated with the absorption spectrum of melanopsin's active isoform is close to the 480 nm wavelength, and the light spectrum associated with the absorption spectrum of melanopsin's inactive isoform is close to the 590 nm wavelength.

In some embodiments, the first amount of light is about 50% of the weighted light 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 weighted light. In another embodiment, the first amount of light is about 25% of 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% of light weighted across the visible spectrum response. That's it. In a further embodiment, the first amount of light is almost all light weighted across the absorption spectrum of one or both of the bistable isoforms of melanopsin. In another embodiment, the second amount of light is outside the absorption spectrum of one or both of the metastable isoforms of melanopsin and / or outside the absorption spectrum of one or both of the bistable isoforms of melanopsin. It is almost all light weighted across the spectrum. In another embodiment, the attenuation of the first amount of light weighted over the absorption spectrum of one or both of the bistable isoforms of melanopsin weighted over the visual spectrum response vs. the attenuation of the second amount of light weighted over the visual spectrum response. The ratio of is greater than work.

In some embodiments, the first amount of light is substantially all light below the wavelength of the long-pass filter within the action potential spectrum of the melanopsin ganglion cells, and the second amount of light substantially corresponds to the wavelength and visible spectrum response above the long-pass filter wavelength. It is all light that spanned. In further embodiments, the first amount of light is substantially all of the light above the short-pass filter wavelength near 590 nm, and the second amount of light can be substantially all of the light across the visible spectrum response at wavelengths less than the short-pass filter wavelength.

In some embodiments, the second amount of light comprises a third amount of light having a wavelength of less than and / or greater than about 590 nm of the maximum relative response of the action potential spectrum of melanopsin ganglion cells. In another embodiment, the second amount of light comprises a third amount of light having a wavelength greater than the maximum relative response of the absorption spectrum of one or both of the bistable isoforms of melanopsin. In a further embodiment, the second amount of light is one or both of the third light amount having a wavelength lower than the maximum relative response of the absorption spectrum of one or both of the bistable isoforms of melanopsin and one or both of the bistable isoforms of melanopsin. It contains a fourth light amount greater than the maximum relative response of the absorption spectrum.

In some embodiments, the first amount of light spans the absorption spectrum of one or both of the bistable isoforms of melanopsin-experienced by cells of the eye-retinal ganglion cells or other cells of the subject (Drec). ) Light amount, the second light amount is the amount of light experienced in the visual response spectrum (Dvis), and the ratio comprising the first light amount and the second light amount is defined as a performance index (FOM), which is determined as follows:

0013

Here, D _rec (T = 1) is the first light amount when there is no optical filter, and D _vis (T = 1) is the second light amount when there is no optical filter. In some embodiments, the performance index of the optical filter may include about 1, about 1 or more, about 1.3 or more, about 1.5 or more, about 1.8 or more, about 2.75 or more, about 3 or more, about 3 or more, about 3.3 or more. . Other performance indices can be used in other embodiments.

In some embodiments, the first amount of light defines a spectral width having a median of the absorption spectrum of one or both of the bistable isoforms of melanopsin. In a further embodiment, the first light amount and the second light amount are determined based on the characteristics of the ambient light. In another embodiment, the first light amount and the second light amount are selectively adjustable by transition, photochromic or electrochromic dye, pigment or coating.

In some embodiments, the optical filter includes at least one layer configured to minimize or reduce the effect of the incident angle of the received light. In a further embodiment, the optical filter further comprises a substrate comprising a color tone by impregnation or coating.

An embodiment of a system for reducing the frequency and / or severity of a photophobia response or adjusting a daily 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 comprises a high refractive index material. The second layer comprises a low refractive index material.

In a further embodiment, the system can include additional layers and / or types of materials, wherein the material transmits less than a first weighted amount of light across the action potential spectrum of melanopsin ganglion cells and the visible spectrum response It is intended to transmit light having a weight greater than or equal to the second light amount. In some embodiments, increasing the number of layers in the optical filter increases light transmission outside the action potential spectrum.

An embodiment of a method of manufacturing an optical filter for reducing the frequency and / or severity of a light sensitive response is described. The method includes determining an appropriate light spectrum. The first amount of light to be experienced by one or both of the bistable isoforms of melanopsin in the subject is determined. The second light quantity associated with the visible response spectrum is determined. An optical filter is produced using the first light amount and the second light amount.

In some embodiments, the action potential spectrum of an individual melanopsin ganglion cell is determined. In another embodiment, the optical filter is configured to attenuate the first amount of light based on the individual melanopsin ganglion cells. In another embodiment, the optical filter is manufactured based on visible response spectral characteristics.

In some embodiments, the optical filter is a notch filter. In another embodiment, the notch filter is configured to block light striking at a normal incidence angle. In another embodiment, the notch filter includes a filter optimized for a plurality of oblique incidence angles. In another embodiment, the notch filter is designed with a slight red shift. In another embodiment, the notch filter includes a filter notch that attenuates light across the spectral width.

In some embodiments, fabrication of the optical filter includes using a dielectric multilayer, embedded nanoparticle coating, color filter, tint, resonant induction mode filter, rugate filter, and any combination thereof. In a further embodiment, the embedded nanoparticle coating is a metallic nanoparticle, dielectric nanoparticle, semiconductor nanoparticle, quantum dot, magnetic nanoparticle or core-shell particle having a core material and a shell material acting as a shell on the core. It includes at least one of. In another embodiment, at least the metallic nanoparticles comprise one or more of Al, Ag, Au, Cu, Ni, Pt or other metallic nanoparticles, wherein the dielectric nanoparticles are TiO ₂ , Ta ₂ O ₅ or other dielectric nano It contains one or more of the particles. In another embodiment, the semiconductor nanoparticles or quantum dots include at least one of Si, GaAs, GaN, CdSe, CdS or other semiconductor nanoparticles. In further embodiments, the shape of the embedded nanoparticles in the embedded nanoparticle coating is spherical, elliptical or other shape. In some embodiments, the extinction spectrum of embedded nanoparticles is determined using Mie scattering theory.

An embodiment of a method of reducing the frequency and / or severity of a light sensitive response or adjusting the daily cycle is described. The method includes receiving a certain amount of light. Light less than the first weighted weight is transmitted across the absorption spectrum of one or both of the bistable isoforms of melanopsin. Through the visible spectrum response, light having a weight greater than or equal to the second light amount is transmitted. Attenuation of weighted light across the absorption spectrum of one or both of the melanopsin's bistable isoforms interferes with the isomerization of one or both of the melanopsin's bistable isoforms.

The drawings constitute a part of the present specification and include exemplary embodiments of the present invention that may be implemented in various forms. It should be understood that, in some cases, various aspects of the invention may be exaggerated or enlarged to facilitate understanding of the invention.
1 shows an example measured action potential spectrum for melanopsin cells normalized to a unit size with Gaussian fitting to the measured data points.
2 shows the measured transmission spectrum of an exemplary “FL-41 35” filter across the “effective action potential spectrum” of melanopsin.
3 shows the measured transmission spectrum of an exemplary “FL-41 35” filter across the visible light spectrum.
4 shows the measured transmission spectrum of an exemplary “FL-41 55” filter across the “effective action potential spectrum” of melanopsin.
5 shows the measured transmission spectrum of an exemplary “FL-41 55” filter across the visible light spectrum.
6 is an example of a filter using a multilayer dielectric thin film having a separate refractive index.
7 is an example of a filter using an embedded nanoparticle coating designed to scatter light in the turquoise region of the visible light spectrum.
8 shows an exemplary method of designing an optical filter to block light absorption by melanopsin cells.
9 shows the measured transmission spectrum of an embodiment of a filter across the “effective action potential spectrum” of melanopsin.
10 shows the measured transmission spectrum of the filter embodiment of FIG. 9 across the visible spectrum.
11 shows the measured transmission spectrum of another embodiment of a filter across the “effective action potential spectrum” of melanopsin.
12 shows the measured transmission spectrum of a further embodiment of a filter across the “effective action potential spectrum” of melanopsin.
13 shows the measured transmission spectrum of another embodiment of a filter across the “effective action potential spectrum” of melanopsin.
14 shows the measured transmission spectrum of the filter embodiment of FIG. 13 across the visible light spectrum.
FIG. 15 shows the measured transmission spectrum of a further embodiment of a filter in which the center of the filter is positioned at 485 nm for normal light incidence across the "effective action potential spectrum" of melanopsin.
FIG. 16 shows the measured transmission spectrum of the embodiment of FIG. 15 with an angle of incidence of 15 degrees across the “effective action potential spectrum” of melanopsin.
17 shows the measured transmission spectrum of another embodiment of a filter excluding the low refractive index MgF ₂ layer across the “effective action potential spectrum” of melanopsin.
18A and 18B show measured transmission spectra of an example of a filter centered at about 480 nm and an example of a filter centered at about 620 nm.
19 shows measured transmission spectra of multiple embodiments of filters centered at about 480 nm with varying degrees of color tone.
20 shows the rear reflection spectrum of the embodiment of the filter of FIG. 19.
21 shows an exemplary embodiment of a method of manufacturing an optical filter.
22 shows an exemplary embodiment of a method for reducing the frequency and / or severity of a photosensitive reaction or adjusting the daily cycle.
23 shows an embodiment of a composite filter configured to preferentially attenuate two ranges of wavelengths.
24 shows an embodiment of a method of manufacturing a composite optical filter.
25 depicts an embodiment of a method of using a composite filter to reduce the frequency and / or severity of photosensitive reactions or adjust the daily cycle.
26A and 26B show transmission spectra of a lens coating of gray color tone centered at 480 nm and 620 nm, respectively.
27 schematically illustrates the periodic isomerization of a bistable pigment.
28 illustrates the reactivity spectrum of active and inactive melanopsin in the eye.
29 illustrates an embodiment of a method that interferes with isomerization of one or both of the bistable isoforms of melanopsin.
30 shows the relative response to the wavelength of light according to the sample color matching function.
31 shows the relative response to the wavelength of light according to the sample color matching function when a 480 nm filter is used.
32 shows the relative response to the wavelength of light according to the sample color matching function when both the 480 nm filter and the 590 nm filter are used.

Detailed description of embodiments of the invention is provided herein. However, it should be understood that the present invention can be implemented in various forms. Therefore, the specific details disclosed herein should not be construed as limiting, but in fact should be construed as a representative basis for teaching those skilled in the art how to employ the invention in any detailed system, structure or manner.

The present invention relates to managing the effect of light on an object. Some applications of the present invention relate to methods, systems and apparatus for reducing the frequency and / or severity of photosensitive reactions or adjusting the daily cycle.

Different individuals experience photosensitive reactions in different ways. The wavelengths and pathways that cause side effects to light can vary from patient to patient. However, there are some common wavelengths that are more commonly associated with photosensitive reactions than others. For example, melanopsin ganglion cells in the eye are sensitive to light at a wavelength of about 480 nm. In some individuals, this may be linked to an individual's light-sensitive neurological condition. Controlling exposure to light near the wavelength of 480nm can benefit individuals and reduce or prevent neurological conditions that are sensitive to light. Alternatively or additionally, controlling exposure to the same light can also help control an individual's daily cycle rhythm. Controlling the eye's exposure to light at or near the 620 nm wavelength, in the same individual or in another individual, may also benefit in reducing or preventing photosensitive neurological conditions or in managing an individual's daily cycle rhythm. The following example relates to attenuation of light with a wavelength near 480 nm and exposure of melanopsin ganglion cells to the same light near 480 nm, but similar filters and methods attenuate light at different wavelengths and would be received by other cells of the eye. It can be understood that it can. For example, similar filters and methods can be used to attenuate light at about 620 nm. In another example, similar filters and methods can be used to attenuate light at about 590 nm.

Since melanopsin ganglion cells are associated with the onset of migraine in patients with photosensitivity and multiple photosensitivity, it is desirable to block at least a portion of that portion of the visible spectrum that activates these cells. Photosensitivity has been linked to light-sensitive neurological conditions, including migraine, benign essential blepharospasm and traumatic brain injury (TBI). 1 shows an example of the action potential spectrum measured for melanopsin cells normalized to unit size and Gaussian fit for the measured data points. This Gaussian pit can be used in at least one embodiment of the filter design, but it should not be interpreted on a spectral basis for the optimal filter, as more refined measurements of the action potential spectrum may be available. Such improved measurements can lead to additional filter designs or methods according to the processes described herein or through similar processes. Optimization of the methods, systems and devices described herein is contemplated based on more refined measurements of the action potential spectrum.

In some embodiments, light may be blocked (ie attenuated) over a specific wavelength range suitable for prevention of photosensitivity while minimizing distortion of the visible light spectrum. In other embodiments, the methods, systems and devices described in this application can also be used to manipulate the body's daily cycle system.

Embodiments of optical filters that block certain portions of the optical spectrum suspected of causing and / or exacerbating these photosensitive reactions are described. These filters include glasses (glasses, goggles, clip-on or other eyewear, etc.), lenses (including contact lenses), computer screens, windows, windshields, lighting substrates, light bulbs (incandescent, fluorescent, CFL, LED, gas vapor, etc.) ), Or other optical elements. These optical filters can be applied to crown glass (including BK7), flint glass (including BaF ₈ ), SiO ₂ , plastics (polycarbonate, CR-39 and TriVex, etc.), other substrates and combinations thereof.

Although much of the description focuses on preventing photosensitization, the systems, methods and devices described herein are applicable to controlling circadian rhythms. For example, this filter can be used to manipulate the body's daily cycle system by businessmen, athletes, people traveling in different time zones, or those who want to manipulate the body's daily cycle system. In one example, subjects will wear at least one of the filters described herein to help them adapt to the light / dark cycle of the area they travel to. In another example, at least one of the filters described herein can also be used to limit excitation of melanopsin ganglion cells in patients with sleep disorders. In this case, the subject can wear these filters to limit exposure to artificial light in the evening, preventing the biological clock from thinking that it is time to stay awake. In addition, users can adjust the light / dark cycle by increasing exposure to light before sunrise.

In addition, it has recently been clinically proven that wavelengths near 620 nm also contribute to the light-sensitizing effect of a particular individual. The exact path to neurological effects is currently not fully understood, but benefits can be obtained by preferentially attenuating light with wavelengths around 620 nm.

Melanopsin has a bistable isoform, each representing a unique absorption spectrum. Isoforms can be active and inactive isotypes. Active isoforms can be physiologically active. The inactive isoform may be physiologically inactive. The absorption of light according to the absorption spectrum of each isotype can lead to isomerization of melanopsin. Advantages can be obtained by attenuating light of about 590 nm or about 590 nm, thereby preventing, limiting or preventing isomerization of melanopsin.

FL-41 lens tone is sometimes prescribed for migraine sufferers. The FL-41 tint blocks (through absorption) a wide range of wavelengths. These wavelengths include those associated with melanopsin absorption. The FL-41 dye can penetrate certain types of plastic spectacle lenses. The amount of dye penetrated generally determines the amount of light blocked. The "FL-41 35" color tone is effective for a large number of patients in an indoor environment. However, if the intensity of the light source increases, for example, by moving to an outdoor environment, “FL-41 35” may not be effective.

2 shows the measured transmission spectrum of “FL-41 35”. Figure 2 also shows the effect of the "FL-41 35" filter on the action potential spectrum of the so-called "effective action potential spectrum" melanopsin. The “FL-41 35” shade blocks or attenuates about 55% of the light, otherwise it is absorbed by melanopsin ganglion cells. The FL-41 tint further blocks a significant portion of the visible spectrum not associated with melanopsin, as shown in Figure 3, and attenuates about 47% for the visible response spectrum. It is undesirable to further block the visible response spectrum. For example, blocking the visible response spectrum can negatively affect normal vision. In another example, blocking the visible response spectrum can produce distraction or less desirable false coloring for the wearer.

For bright light, such as in outdoor environments, a tint with a greater level of spectral attenuation such as "FL-41 55" can be used. The transmission spectrum of this filter, along with its effect on the action potential spectrum, is shown in FIG. 4 (for Melanopsin's “effective action potential spectrum”) and FIG. 5 (for the visible light spectrum). This filter attenuates about 89% of light and is otherwise absorbed by melanopsin cells, but also attenuates about 81% of the visible response spectrum. This additional spectral attenuation can impair vision in low light or other situations.

Overall, the general drawbacks of FL-41 are rose-colored appearance, distorted color recognition; Limited applicability (i.e., only applicable to certain plastics and not to glass lenses, computer screens, windows, windshields, lighting substrates, light bulbs or other optical elements); And poor quality control for the coloring process (due to some changes in the colorable hard coating layer). Although FL-41 may be effective in certain applications, it is not designed to down-regulate the stimulation of melanopsin ganglion cells and their connection to the pain center of the brain. For this reason, it may be desirable to develop other embodiments of filters.

An example of a more preferred optical filter for the treatment of photosensitive conditions may include a long wavelength pass filter. To control the exposure of melanopsin ganglion cells to a wavelength of about 480 nm, a long wavelength pass filter can attenuate light at wavelengths shorter than about 500 nm or 520 nm, while transmitting wavelengths longer than about 500 nm or 520 nm. Similarly, to control the exposure of cells in the human eye to a wavelength of about 620 nm, a short-wavelength pass filter transmits high wavelengths shorter than 600 nm or about 580 nm while attenuating light at wavelengths longer than about 600 nm or about 580 nm. Can be.

Another example of a more preferred optical filter is to block only the spectrum of light absorbed by melanopsin or other specific wavelengths, while generally transmitting the remaining light spectrum, and the filter's spectral transmission response is in the form of a notch, also called a band stop or minus filter. To take. In the case of melanopsin, the central location of the notch may be close to the maximum absorption of the melanopsin pathway (about 480 nm), but other locations may be effective. The spectral width of the notch can roughly match the width of the action potential spectrum of about 50 to 60 nm, although other widths are contemplated.

Optical filter technologies such as tints made of a dye mixture, dielectric multilayer (example shown in Figure 6), and embedded nanoparticle coating (shown in Figure 7), other filter technologies such as resonant waveguide filters, or combinations thereof It can be used to create filters according to the invention. Nanoparticle coatings that can be used in optical filters according to the present disclosure include metallic nanoparticles (e.g., Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g., TiO ₂ , Ta ₂ O ₅ Etc.), semiconductor nanoparticles or quantum dots (e.g., Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell particles composed of one substance in the core and other substances acting as a shell, other nano Particles, or combinations thereof. The shape of the particles can be spherical, ellipsoidal, other shapes, or a combination thereof. The host material can include polymers, sol-gels, other host materials, or combinations thereof. The extinction spectrum of these nanoparticles can be calculated using Mie scattering theory or variations thereof.

The embodiment of the multi-layer filter 600 illustrated in FIG. 6 includes a substrate 602, a first layer 604, and a second layer 606. As shown, the first layer 604 can include a high refractive index material, and the second layer 606 can include a low refractive index material. In other embodiments, the first layer 604 can include a low refractive index material, and the second layer can include a high refractive index material. Also, the first layer 604 is shown adjacent to the substrate 602. In other embodiments, the first layer 604 can have other layers (eg, the second layer 606 and / or other layers) between the substrate 602 and the first layer 604. Additional layers (not numbered) are also indicated. The substrate 602 can use any of the substrates described herein. For example, the substrate 602 may have a colored layer (not shown) on the same and / or opposite sides of the first layer 604 and the second layer 606 (ie, the front and / or back side of the substrate). It can contain. In another example, the substrate 602 itself may be tinted. Examples of coloring techniques and amounts are described below. Other embodiments of the multilayer filter are further described herein.

The filter 700 shown in FIG. 7 includes a substrate 702, a host layer 704 and a plurality of nanoparticles 706. The host layer 704 is shown adjacent to the substrate 702. In other embodiments, the host layer 704 may have another layer (eg, the second layer 606 and / or other layer in FIG. 6) between the substrate 702 and the host layer 704. The nanoparticles 706 are spherical and shown in a uniform size, but other shapes and sizes are contemplated as described above. As in the multi-layer filter of FIG. 6, various substrates, shades, other features, or combinations thereof can be used with the nanoparticle filter 700. Other embodiments of nanoparticle filters are described herein.

Other types of filters that can be used may include color filters (organic dyes and semiconductors), resonance induction mode filters, rugate filters, or combinations thereof. The lugate filter utilizes a sinusoidal refractive index change across the thickness. Actual sine waves are often approximated by a step index approximation using a mixture of two or more materials.

In addition to these various filter types, the effect of designed filters on the visible response spectrum can be further considered, as determined by the light response of the rod and cone cells. One consideration may include minimizing spectral distortion. For example, by attenuating light near 480 nm approaching melanopsin ganglion cells, by designing the center of the notch to shift slightly red at about 480 nm to account for the blue-shift of the filter response that occurs for off-axis illumination, It may be contemplated to add additional or other constraints to the filter design, including optimization methods such as taking into account angular sensitivity that can be compensated using a dielectric multilayer. Depending on the attenuated wavelength, the degree of red shift or blue shift may be different. Optimization may further include widening the filter spectral width through the use of additional filter layers to compensate for the non-normal incident angle and / or to compensate for the incident angle. The possibility of back reflection can be considered. One or more of these considerations can be addressed by combining the filter with some form of coloring.

One embodiment of a method of manufacturing an optical filter that blocks light absorption by melanopsin cells is described herein. The amount of light D experienced by melanopsin cells can be recorded as follows:

[Equation 1]

Where L is the light spectrum (intensity, power, photons / second, etc.), T is the spectral transmission of the filter placed between the light source and the eye, and M is the normalized action potential response spectrum of melanopsin. It is estimated from the maximum half width of 52 nm to the total width of 480 nm, as shown in FIG. 1, as a mantissa function. In general, L = 1 is assumed to not limit discussion to any particular light source, but analysis can be performed on any light source in a known spectrum.

Similar light quantities in relation to the visible response spectrum can be calculated as follows:

[Equation 2]

Where V represents the standardized visual response spectrum.

The effect of an optical filter, such as the FL-41 tint, is to reduce the amount of light, as explained, for example, taking into account the ratio of the amount of light calculated by the filter to the amount of light without a filter.

The "attenuation" of the capacity can be recorded, for example, as follows:

A performance index (FOM) comparing the blocking of the melanopsin response with the blocking of the visible response spectrum can also be defined as follows:

[Equation 3]

This represents the ratio of the attenuation of light across the melanopsin spectrum to the attenuation of light across the visible spectrum, where a value of FOM> 1 may be desirable. For the FL-41 tint, the FOM is about 1.

FIG. 8 blocks light absorption by melanopsin cells, which may include determining the amount of light D experienced by melanopsin cells (eg, using Equation 1), as illustrated by step 802. To illustrate, one embodiment of a method 800 for designing an optical filter. As illustrated by step 804, the amount of light experienced over the visible response spectrum can be determined (eg, using Equation 2). The performance index (FOM) can be determined for the amount of light experienced by melanopsin cells and the amount of light experienced over the visible response spectrum, as described in step 806. In other embodiments, the capacity across the visible response spectrum can be reduced or separated. For example, a portion of the visual response spectrum can be used, or wavelengths outside the visual response spectrum can be considered. The performance index can be used to design optical elements to reduce and / or prevent light sensitive responses.

Many of the embodiments described herein use a multilayer dielectric thin film having a separate refractive index. These layers can be applied to a number of optical elements (as described herein). By way of example, and not limitation, embodiments of the optical filter design of the present disclosure are typical transparent substrates, such as spectacle lenses, having a refractive index of about 1.5 and an anti-reflective coating applied to the back side (ie, the surface closest to the user's eye). Suppose Thus, other substrates with different refractive indices and with or without a back antireflective coating are contemplated. Filter designs may require some modification to compensate for different substrate materials and / or different coatings for these substrates. Additional considerations such as compatibility of different thin film materials with other substrate materials and curvature of the lens substrate need to be addressed. The substrate may include an adhesive layer (eg, a thin layer of chromium) between the substrate or a layer on the substrate and another coating layer.

There are a number of design approaches for multilayer long wavelength pass and notch filters that can be used. For example, software and other design tools can be used to design thin film optical filters. These tools can take into account multiple constraints during optimization, reducing the likelihood that the two filter designs will be the same, even if they achieve the same shading properties or produce the same physiological results. Only a few examples are presented herein and are not intended to be limiting in any way. According to the present invention, other approaches can be taken to achieve similar results, and further optimization can be performed to create more ideal properties or similar properties with fewer layers.

In addition, multilayers and other coatings can be applied to colored lenses or substrates. There are several reasons why this combination is desirable. One reason may include that the spectral properties of the color tone can alleviate design constraints for thin film filters. For example, combining FL-41 "base tone" with a thin film notch filter can serve to reduce the depth of the notch needed to produce a therapeutic result. It may be desirable to take into account the change in the transmission spectrum of the color tone in the notch design. This design adjustment can be achieved, for example, by shifting the center wavelength of the notch to compensate for the local slope of the hue spectrum response. Another reason to use a basic tint may be to reduce undesirable reflections of light coming through the back of the lens. In this situation, it may be desirable to use a “flat” or neutral density, color tone that does not cause coloration on its own.

For example, in an embodiment of a filter designed to block the wavelength range of light from passing through the front of the lens (e.g., by reflecting the desired wavelength away from the user), the lens (including light at a blocked wavelength) Light entering the rear side of the may be reflected back to the user's eyes. In other words, light to be blocked from the front (by reflection in the case of a multi-layer filter) can be reflected from the rear. This may not be a problem, mainly if there is a single light source in front of the object. However, for example, where very bright light is found or where there are multiple light sources, this back reflection can be harmful to the user.

One exemplary approach to making a long wavelength pass or notch filter involves using alternating layers of high and low refractive index materials. Examples of low refractive index dielectric materials include MgF ₂ and SiO ₂ . MgF ₂ is commonly used for single and multilayer antireflective coatings. Examples of high refractive index materials include metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ and Ta ₂ O ₅ and Si ₃ N ₄ . Numerous other suitable materials can be used, including polymer layers.

Optical filters for attenuating light near various wavelengths, such as 480nm, 620nm, or other specific wavelengths, can follow a similar design. One embodiment of the optical filter design is shown in FIGS. 9 and 10, and the effect of the filter of this embodiment on the spectrum of light striking melanopsin cells generating effective (and attenuated) action potentials is also shown. This design is clinically effective as the FL-41 35 coating in that 55% of the light that can be absorbed by melanopsin cells is blocked or attenuated, thereby mitigating the same migraines (or photosensitivity) as the FL-41 coating. Results, but the visual distortion is fairly small, and only 18% attenuates over the visual response. In this embodiment, the low refractive index material is SiO ₂ and the high refractive index materials TiO ₂ and MgF ₂ are used as the outermost layers, so a total of 11 layers are used. Exemplary layers and materials are listed in the table below, from the outermost layer (MgF ₂ ) to the innermost layer adjacent to the substrate (TiO ₂ of 165 nm thickness). In this filter, it is FOM ≒ 3.

The spectral position of the center of the notch filter can be determined by the thickness of each layer. There are many embodiments that assume that the notch's spectral position is at about 480 nm, but other spectral positions can be considered. For example, since more information is known about the action potential spectrum of the melanopsin pathway, the spectral position can be shifted to 620 nm according to the new information. In other examples, spectral positions can be positioned to achieve specific results, such as attenuating wavelengths other than the action potential spectrum of the melanopsin pathway.

The width of the notch can be determined by the difference in refractive index of different layers. The depth of the notch can be determined by the number of layers. Transmission outside the notch area can be increased and planarized, including additional layers, and possibly includes a single or multilayer anti-reflective coating applied to the back side of the lens to reduce back reflection. Additional design optimizations can be used to increase the depth of the notch that can further inhibit excitation of melanopsin cells, but the impact on the visible response spectrum must be considered. The overall suppression can be customized by designing one or more common types of filters to help per patient or in most cases.

Greater attenuation of the effective melanopsin action potential spectrum can be obtained by deepening or widening the filter notch, or a combination of the two. 11 and 12 show examples of two exemplary approaches, using 19 and 15 dielectric layers, respectively. The ultimate choice between the two can be made based on wearer preferences, both producing about 70% attenuation across the melanopsin spectrum, but the visible response spectrum properties are slightly different. The 19-layer filter attenuates about 21% of the visual response spectrum, and the 15-layer filter attenuates about 25% of the visual response spectrum. Both filters have a FOM value greater than 2.75, and the 19 layer filter has a FOM value of about 3.3.

Different designs can achieve significant attenuation across the melanopsin action potential spectrum. 13 and 14 show an example of a notch filter design that produces a melanopsin action potential attenuation similar to the FL-41 55 filter, using 19 dielectric layers to block about 89% light, but with a FOM value of about At day 3, only about 29% of the visible response spectrum is blocked. Exemplary layers and materials from the outermost layer (MgF ₂ ) to the innermost layer adjacent to the substrate (160.3 nm thick TiO ₂ ) are listed in the table below.

Other design considerations may include blocking colliding light at irregular incident angles. For example, tilting the angle of the thin film filter tends to cause blue shift in the filter response. This can be accommodated to minimize or reduce the effect of the angle of incidence, for example by intentionally designing the filter with a slight red shift, to widen the filter, add an additional layer, or a combination of these.

15 shows an embodiment of a filter design with 10 layers where the center of the notch is located at 485 nm for normal light incidence. At normal incidence, this embodiment of the filter blocks about 61% of the light for the melanopsin spectrum and attenuates about 21% for the visible response spectrum, resulting in a FOM value of about 2.9.

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

This embodiment of the filter has the following layer properties listed in the table below, from the outermost layer (MgF ₂ ) to the innermost layer (TiO _{2 with a} thickness of 127 nm).

In the embodiment of the filter described with respect to Figures 8-15, a low refractive index MgF ₂ layer was used. In other embodiments, this material may not be necessary. For example, FIG. 17 shows an embodiment of a filter design with a FOM value of about 3.5, blocking about 73% of the melanopsin action potential spectrum (or light amount) and about 21% of the visible response capacity. The layer properties of the filter design shown in FIG. 17 are listed in the table below from the outermost layer to the innermost layer.

As discussed above, it may be desirable to reduce the amount of light reflected from the back side (ie, the side closest to the user's eye) to the user's eye. This can be achieved by other embodiments of filter design in which a thin film coating can be applied on a colored lens or substrate. In other embodiments, the substrate can be colored by impregnation, coating, other coloring techniques, or a combination thereof. The transmission of light through the thin film coating / colored substrate combination can be recorded as the product of the transmission of the thin film coating and the transmission of the colored substrate as follows:

[Equation 4]

It is assumed that the thin film coating is applied only to the front side of the substrate, and that the antireflective coating (T ≒ 1) is applied to the back side of the substrate.

Light incident on the back side of the substrate first passes through the color tone, is reflected from the thin film filter on the front side of the substrate, and then passes through the color tone secondly before hitting the user's eyes. In this case, the reflected light can be recorded as follows:

[Equation 5]

At any particular wavelength, the ratio of transmitted and reflected light can be set by thin film coating and transmission of color tone. For example, if about 20% transmission is desired at a desired wavelength (about 480 nm in this example), only certain combinations of thin film and color transmission can be used. Moreover, if about 10% reflection is desired, only a single combination of thin film and color transmission is allowed. This relationship can be explained as follows.

[Equation 6]

[Equation 7]

The dose D experienced by melanopsin cells due to light reflected back to the user's eyes can be recorded similar to the dose experienced by melanopsin cells due to the transmitted light shown in Equation 1:

[Equation 8]

Where L is the light spectrum (at intensity, power, photons / sec, etc.), R is the spectral back reflection, M is the normalized action potential response spectrum of melanopsin, and centers 480 nm with a maximum half-width premise width of 52 nm from FIG. As the Gaussian function of is as currently expected. In general, it is assumed that L = 1 so as not to limit the discussion of any particular light source, but analysis can be performed on any light source of a known spectrum.

The retroreflected normalized amount experienced by melanopsin cells can be calculated as follows:

[Equation 9]

Similar and normalized quantities can be calculated in relation to the visible response spectrum.

[Equation 10]

[Equation 11]

Here, V represents a standardized visual response spectrum. Ideally, the back reflection will be reduced so that this amount of light approaches zero.

The amount of back-reflected light with respect to the action potential spectrum of the melanopsin pathway can be determined using Equation (8). The amount of light of the back-reflected light for the visual spectrum can be determined using Equation (9). The amount of reflected light can be used to design and manufacture optical filters. For example, an appropriate tint level can be selected based on the desired maximum amount of back light reflected back light, depending on whether the action potential spectrum of the melanopsin pathway, or the visible spectrum, or both. The reduction in the amount of back-reflected light and normalized amount experienced by melanopsin cells can reduce the symptoms experienced by light-sensitized users.

The following table shows a further embodiment of a filter design with some possible combinations of notch and tint transmissions causing specific transmissions and back reflections, for example at about 480 nm. Due to the notch response, light transmission outside the notch may be greater than light transmission inside the notch, so the amount of back reflected light will be less than that occurring in the center of the notch. These examples are specific for notches centered around 480 nm, but other wavelengths can be selected as described herein.

Table 1 provides an example of maintaining a fixed 10% back reflection at a specific wavelength (eg, around 480 nm) or wavelength range with different transmissions through the front. The value of this back reflection can be used, for example, in an “open” type eyeglass frame where light hits the lens from the top, bottom and / or side and enters the back of the lens and reflects from the front side thin film coating to the user's eye. May be desirable for therapeutic lenses. Other back reflections may be desirable for different styles of eyeglass frames (such as sports glasses, wraparound sunglasses or other styles of frames).

Transmittance T Rear reflection R T _tint T _film 0.50 0.10 0.65 0.77 0.45 0.10 0.61 0.73 0.40 0.10 0.57 0.70 0.35 0.10 0.54 0.65 0.30 0.10 0.50 0.60 0.25 0.10 0.47 0.54 0.20 0.10 0.43 0.46 0.15 0.10 0.40 0.38 0.10 0.10 0.37 0.27

Table 2 provides additional examples, but larger back reflections are allowed. Such a design may be more suitable for "warp" type glasses or sports frames that prevent light from entering the eye, except for light passing through the front side of the lens.

Transmittance T Rear reflection R T _tint T _film 0.50 0.35 0.89 0.56 0.45 0.35 0.86 0.52 0.40 0.35 0.82 0.49 0.35 0.35 0.79 0.44 0.30 0.35 0.76 0.39 0.25 0.35 0.73 0.34 0.20 0.35 0.70 0.29 0.15 0.35 0.67 0.22 0.10 0.35 0.64 0.16

Other embodiments of the filter may include fixing the notch transmission and adjusting the color tone transmission to provide a given back reflection value. Examples of these examples are presented in Table 3 below.

Transmittance T _film Rear reflection R T _tint trans T 0.35 0.05 0.28 0.10 0.35 0.10 0.39 0.14 0.35 0.15 0.48 0.17 0.35 0.20 0.55 0.19 0.35 0.25 0.62 0.22 0.35 0.30 0.68 0.24 0.35 0.37 0.75 0.26 0.25 0.45 0.77 0.19 0.15 0.50 0.77 0.12

The R value herein can be used to determine the maximum amount of back reflected light. For example, an R value of about 0.10 can be used as the amount of desired back reflected light weighted across the action potential spectrum, visible spectrum, or both of the melanopsin pathway. Since the R value is based on the desired wavelength to attenuate, the wavelength of other light can be attenuated based on a filter designed to achieve an R value below the value according to the table above. For example, for a wavelength of about 480 nm with an R value of about 0.10, the R value for a wavelength of about 470 nm or 490 nm may be less than 0.10, for example about 0.09. The R value will generally decrease at a wavelength away from the desired notch center wavelength. For clarity, the R values are listed in the table as decimal values, but these values may be expressed as percentages.

These examples are not intended to limit combinations that are suitable for the present disclosure and are provided only to demonstrate some of the possible combinations that may be suitable for therapeutic effect. Any number of different combinations can be envisioned, suitable for different levels of user sensitivity, different diseases, different applications, different types of shades (eg, gray, FL-41, etc.), and different frame styles.

Manufacturing considerations may also be considered when performing filter design. For example, material deposition is typically accomplished using sputtering, evaporation, or chemical vapor deposition techniques. Deposition conditions can be optimized to minimize the stress of the thin film material. High temperature annealing can often be performed after deposition to relieve stress in the deposited material, but annealing is often not applicable to plastic lenses. Since the spectacle lens exhibits a curved substrate, it can be difficult to achieve a constant film thickness during deposition. To create a constant film thickness, modification of the target-source geometry in the deposition system can be used. For plastic lenses, low temperature deposition can be used, but can be optimized to produce a low stress film.

The following working example describes the tested optical filter design and its results. Test notch coatings are made from scratch-resistant coated polycarbonate or CR-39 planar lenses. A thin film of Cr was deposited on the substrate to act as an adhesive layer for the thin film stack. The transmission spectrum through an exemplary coated lens is shown in FIG. 18A. The center of the notch is about 482.9nm with a width of about 54.5nm, and the minimum transmittance is about 24.5%. This embodiment of the filter blocks about 58% of the melanopsin action potential spectrum, blocks about 23% across the visible spectrum, and has a FOM value of about 2.6. In contrast, FIG. 18B shows the transmission spectrum of a coated lens with a 620 nm notch filter.

In a preliminary clinical trial, migraine sufferers were recruited to wear glasses with the therapeutic notch coating of FIG. 18A. Participants wore therapeutic lenses for 2 weeks. To be included in the trial, all participants had a chronic headache, which is defined as having a headache of 15 days or more per month. A validated questionnaire, HIT6, was used to evaluate the impact of headaches on participants' daily life before and after wearing therapeutic lenses. The table of HIT6 scores is shown in the following table. The average improvement was about 6.6% and the quality of life of the participants was greatly improved.

In another embodiment, a thin film notch coating was applied to the FL-41 tinted lens. The transmission and back reflection spectra are shown in Figures 19 and 20. Different levels of FL-41 tint were applied to the colorable scratch resistant layer (also called hard coating) on polycarbonate or CR-39 lenses. Subsequently, a multi-layer notch filter was applied to the front of each lens, and a conventional anti-reflective coating was applied to the back of each lens. As can be seen in Figures 19-20, the FL-41 color tone dramatically reduced back reflection. However, the notch response upon transmission becomes red due to the slope of the FL-41 tint near 480 nm. This shift can be compensated by starting a notch design with a slight blue shift.

The following table lists the melanopsin and blocking levels across the visual response spectrum and FOM values for each tint level. Similar results can be expected using other shades, such as BPI's “sun gray” shades of gray.

The coatings described herein can also be incorporated with other technologies. For example, the filter coating can be applied to a tinted lens, a photochromic material can be included, a polarization technique can be included, and other techniques or combinations thereof can be incorporated. In addition, a combination of filter techniques such as applying a nanoparticle filter coating over a multi-layer thin film coating can be used. Electro-optical materials including electro-optical polymers, liquid crystals, or other electro-optical materials, piezoelectric materials including piezoelectric ceramics such as PZT, or active materials such as other piezoelectric materials can be used.

21 depicts an exemplary embodiment of a method 2100 of manufacturing an optical filter for reducing the frequency and / or severity of a light sensitive response. Method 2100 can be used to design at least one embodiment of a filter described herein. Method 2100 can include determining an appropriate light spectrum, as illustrated by step 2102. Determining the appropriate light spectrum may include spectrophotometric measurements under conditions such as indoor fluorescent lighting and / or computer screens in an office, shopping or home environment, or outdoor light such as sunshine due to normal outdoor or sports activities. The same may include consideration of specific lighting conditions. As illustrated by step 2104, the amount of light to be experienced by melanopsin cells can be determined (eg, using Equation 1). The amount of light to be experienced over the visible response spectrum can be determined (eg, using Equation 2), as illustrated by step 2106. The optical filter can be designed and manufactured using the first light amount and the second light amount, as described in step 2108. The first light amount and the second light amount can be used to determine a performance index (FOM) as described herein. In other embodiments, the amount across the visual response spectrum can be considered for a portion of the visible spectrum. For example, more or less than the entire visual response spectrum can be used.

22 depicts an exemplary embodiment of a method 2200 for reducing the frequency and / or severity of a photosensitive response or adjusting the daily cycle. Method 2200 can be used with at least one embodiment of the described filters. Method 2200 can include receiving the amount of light, as illustrated by step 2202. The received light may include direct or indirect light from one or more light sources. As shown by step 2204, an amount of light less than the first amount of light weighted across the action potential spectrum of the melanopsin cells can be transmitted, as shown by step 2206. The second amount of light weighted over the visible light spectrum can be transmitted, as shown by step 2208. As shown in step 2208, an optical filter can be manufactured using the first light amount and the second light amount. The first light quantity and the second light quantity can be used to determine a performance index (FOM) as described herein. In other embodiments, the amount across the visual response spectrum can be reduced or separated. For example, more or less than the entire visual response spectrum can be used.

In addition to regulating melanopsin ganglion cells' exposure to light near 480nm, clinical trials have demonstrated that attenuation of light at a wavelength of about 620nm may also improve improvements in alleviating symptoms associated with light sensitivity. . Although a light wavelength of about 620 nm is not believed to act on melanopsin ganglion cells, light attenuation of about 620 nm reduces symptoms of light sensitivity in some people, such as pain or discomfort to light, and the severity of migraine and other headaches It can also be effective in the treatment of blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy.

In one embodiment, an improvement may be realized by attenuating light between about 580 nm and about 650 nm. In other embodiments, improvements may be realized by attenuating light between about 600 nm and about 640 nm. In another embodiment, the improvement can be realized by attenuating light using a filter that is substantially centered at a wavelength of 620 nm with a full width at half maximum of about 55 nm.

In addition, filters can attenuate multiple ranges of light wavelengths. For example, an embodiment of the filter may attenuate light at about 620 nm in addition to attenuating light at about 480 nm. In other embodiments, the filter may preferentially attenuate light wavelengths from about 450 nm to about 510 nm and from about 580 nm to about 640 nm. In yet another embodiment, the filter can attenuate light between about 470 and about 490 and between about 610 nm and about 630 nm.

The optical filter can be made using the materials described above according to the process described above. For example, the 620 nm optical filter can include a high pass filter, a low pass filter or an optical notch filter. The optical notch filter may include a plurality of layers of dielectric material, nanoparticles dispersed on the host medium or embedded in the host medium, or combinations thereof. Also, any of the above-mentioned combinations can be used with the dye incorporated into the substrate. For example, creating a short-pass pass or notch filter can include using alternating layers of high and low index materials. Examples of low refractive index dielectric materials include MgF ₂ and SiO ₂ . Examples of high refractive index materials include metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ and Ta ₂ O ₅ and Si ₃ N ₄ . Numerous other suitable materials can be used, including polymer layers.

An optical filter intended to attenuate the wavelength absorbed by melanopsin ganglion cells and designed to attenuate the wavelength at about 620 nm, similar to the previously described embodiment, can be made according to a similar FOM. The amount of light D received at about 620 nm can be recorded as follows:

[Equation 12]

Where L is the light spectrum (intensity, power, photons / second, etc.), T is the spectral transmission of the filter placed between the light source and the eye, R ₆₂₀ is the ideal response spectrum at about 620 nm, which is half of 50, 55 or 60 nm It can be estimated with a Gaussian function centered on 620 nm at the maximum overall width, but other values may also prove to be expected and therapeutic. In general, it is assumed that L = 1 so as not to limit the discussion of any particular light source, but analysis can be performed on any light source of a known spectrum.

Similar amounts can be calculated with respect to the visible response spectrum.

[Equation 13]

Here, V represents a standardized visual response spectrum.

The effect of an optical filter, such as a nanoparticle notch filter, is the ratio of the capacity calculated by the filter to the capacity without the filter, for example,

As described above, the light quantity is reduced.

The "attenuation" of the capacity can be recorded, for example, as follows:

A FOM can also be defined that compares the blocking of the light to the visible response spectrum at about 620 nm.

[Equation 14]

This represents the ratio of the attenuation of light at about 620 nm to the attenuation of light over the visible spectrum, where a value of FOM> 1 may be desirable. Using the method described above to estimate the visual response at about 620 nm, the comparison becomes more stringent when a smaller overall width half maximum value is used. For example, if the Gaussian distribution R (λ) used in the estimation has a full width half maximum of 50 nm, a more specific optical filter can be created when the estimate includes R (λ) with a full width half maximum of 60 nm. have.

The optical filter may comprise a multilayer dielectric film similar to that described for the attenuation of sensitive light by melanopsin cells, or the optical filter may be a nanoparticle-based optical filter, color filter, color tone, resonance guided mode filter, lugate filter, or combinations thereof. It may include. The nanoparticle-based optical notch filter can include nanoparticles embedded on or on the surface of the host medium. Thus, these filters can be used in a substantially transparent host medium, such as the lens material of eyeglasses, or simply applied to the surface. For example, a filter can be placed on the surface of the spectacle lens to attenuate light approaching the user's eye. In other applications, the filter may be placed directly on the light source, such as on an electronic display or light bulb, such as a computer screen, or the emission of light by a nanoparticle based notch filter may result in the shape of the nanoparticle, on the host medium, or The amount or density of the embedded nanoparticles, the composition of the nanoparticles, the size of the nanoparticles and the refractive index of the host medium can be adjusted. Therefore, the attenuation spectrum of the nanoparticle-based optical notch filter can be adjusted to a specific curve by selecting the material and distribution centered on the curve at the desired wavelength, and the attenuation curve with the desired wavelength value and proper shape and maximum attenuation at half full width To create.

For example, increasing the refractive index of the host medium of the nanoparticles can shift the attenuation spectrum to longer wavelengths, such as using larger particles and / or other metals, including solid and core-shell particles. The attenuation spectrum changes because attenuation is at least partially due to localized surface plasmon resonance (LSPR). The scattering caused by LSPR is proportional to the relative refractive index of the host medium. Therefore, when the refractive index of the host medium increases, the attenuation spectrum not only shifts red, but also increases the amount of scattering and thus the amount of attenuation of light.

The location and amount of scattering due to LSPR depends at least in part on the relative refractive index between the particle and the host medium. Therefore, the relative refractive index can also be changed by changing the nanoparticle composition. The nanoparticles can be a single material, or a solid consisting of a core-shell composition having a core of a first material and a shell of a second material. In either case, the material can be a single element, compound or alloy. As described above, the nanoparticles are metallic nanoparticles (eg Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (eg TiO ₂ , Ta ₂ O _5, etc.), semiconductor nanoparticles or quantum dots (Eg, Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell particles composed of one material in the core and the other acting as a cell, and other nanoparticles, or combinations thereof. For example, increasing the proportion of Ag in Ag / Al alloy solid nanoparticles can shift the red color and increase the amplitude of the attenuation curve for the nanoparticles.

In addition, the nanoparticles used may have a cross section comprising a circle, ellipse, rectangle, hexagon, octagon, or other polygon. Spherical particles have the most concentrated spectrum because they have a single narrow primary peak that can be optimized using size and composition changes. However, it is possible to use a combination of particles of different shapes to develop the desired filter spectrum. For example, by simply introducing cubic nanoparticles or octahedral nanoparticles of the same size, the extinction spectrum of a 40 nm spherical nanoparticle filter can be widened.

In contrast, the attenuation curve of the core-shell nanoparticles can be adjusted by changing the relative thickness of the core and shell. As an example, reducing the thickness of the Ag shell relative to the size of the SiO ₂ core can reduce the maximum half of the overall width of the attenuation spectrum. The shape of these particles can be spherical, ellipsoidal, other shapes, or a combination thereof. The shape of the particles can also affect the shape and amplitude of the damping curve. In one embodiment, the optical filter comprises spherical core-shell nanoparticles. In a further embodiment, the spherical core-shell nanoparticles have an Ag shell and Si core. In another embodiment, the spherical Ag / Si core-shell nanoparticles have an Ag shell with a radial thickness of 45 nm and a Si core with a radius of 15 nm.

23 shows a nanoparticle based optical filter used with a multilayer thin film filter to form a composite thin film filter 2300. The first filter can attenuate light in the first range of wavelengths, thereby substantially reducing or eliminating those wavelengths of the light spectrum incident on the second filter. In the illustrated embodiment, ambient light 2302 may enter a filter comprising nanoparticles 2304 that may be disposed or embedded on a host medium 2306 disposed on the surface of thin film filter 2308. Alternatively or additionally, thin film filters and nanoparticle based filters can be disposed on opposite surfaces of a substrate, such as spectacle lenses. In other embodiments, nanoparticles can be embedded within a thin film filter, and one or more layers of the thin film can be a host medium for the nanoparticle based filter. The ambient light 2302 entering the host medium 2306 in which the nanoparticles 2304 are buried may be sunlight. The attenuated light 2310 entering the thin film filter 2308 may have a reduced amount of light in a range attenuated by the nanoparticles 2304. The filtered light 2312 exiting the composite filter 2300 may be attenuated in two wavelength ranges. Similarly, a “double notch” filter can be fully implemented through the use of a multi-layer thin film coating.

24 shows an embodiment of a method 2400 of manufacturing a composite optical filter for reducing the frequency and / or severity of a light sensitive response. Method 2400 can be used to design at least one embodiment of the composite filter described herein. Method 2400 may include determining an appropriate light spectrum, as shown by step 2402. Determining the appropriate light spectrum may include spectroscopic measurements under conditions such as indoor fluorescent lighting and / or computer screens in an office, shopping or home environment, or outdoor light such as sunlight experienced due to normal outdoor or sports activities. As may be done, it may include consideration of specific lighting conditions.

As illustrated by step 2404, the first amount of light to be experienced by the subject can be determined (eg, using Equation 1). The second amount of light to be experienced by the human eye at a wavelength of about 620 nm can be estimated as illustrated by step 2406 (eg, using equation (12)). As illustrated by step 2408, the third amount of light to be experienced over the visible response spectrum can be determined (eg, using Equation 13). The optical filter can be designed and manufactured using the first light amount, the second light amount, and the third light amount, as illustrated by operation 2410. The first light amount and the second light amount are each used together with the third light amount to determine a performance index (FOM) for each as described herein. In other embodiments, the amount of light across the visual response spectrum may be considered for some or part of the visible spectrum. For example, more or less than the entire visual response spectrum can be used.

25 depicts an embodiment of a method 2500 using a composite filter to reduce the frequency and / or severity of a photosensitive reaction or to adjust the daily cycle. Method 2500 may be used with at least one embodiment of the composite filter described herein. Method 2500 may include receiving a certain amount of light, as illustrated by step 2502. The received light may include direct or indirect light from one or more light sources. As illustrated by step 2504, a first amount of light that is preferentially attenuated across the action potential spectrum of melanopsin cells can be transmitted. As illustrated, a second amount of light preferentially attenuated in the wavelength range at about 620 nm may be transmitted. Thereafter, as illustrated by step 2508, a third amount of light can be transmitted to the human eye. In other embodiments, the amount across the visual response spectrum can be reduced or separated. For example, more or less than the entire visual response spectrum can be used.

Efficacy tests were conducted to verify the benefits of attenuating light at about 480 nm and around 620 nm. Preliminary trials included a preliminary double mask crossover clinical study to determine the effectiveness of a custom thin-film glasses coating in the treatment of chronic migraine. During the test, subjects wore two different glasses: one coating was a notch filter at 480 nm and one coating was a notch filter at 620 nm. Typical transmission spectra of gray tinted lenses with different coatings used in this study are shown in FIGS. 23A and 23B. The 480nm notch filter blocks approximately 68% of light absorption by melanopsin and blocks 42% of visible light. The 620nm notch filter blocks about 66% of light absorption centered on 620nm at ~ 55nm width and blocks about 42% of visible light. The 480nm filter used in this study blocked 68 ± 6% of the approximately 480nm, and the average visible light blocked 44 ± 4%. The 620nm filter used in this study blocked 67 ± 2% of the average about 620nm, and the average visible light blocked 43 ± 4%. Neither the subject nor the clinical coordinator knows which lens has a 480nm notch filter and which lens has a 620nm notch filter. The subject of the study had to perform a diagnosis of chronic migraine, which means that he had more than 15 headaches per month. Individuals with a headache of at least 15 days a month are considered to be the most severely affected migraines.

To assess the effectiveness of the intervention, six questions "headache impact test" ("HIT-6") were selected as the primary outcome measure. HIT-6 is a six-question tool designed and tested to assess the impact of headaches on a person's life. The score is a continuous variable from a minimum of 36 to a maximum of 78. A score less than 50 indicates that the headache has little effect on one's life, and a score of 50-55 indicates a “some effect”. 56-59 indicate “substantial impact” and scores of 60 or higher indicate “very serious impact” of headaches.

Subjects first completed a 4 week “pre-clean” without wearing study lenses. This period helps to establish the basic characteristics of their headaches. Block randomization was used to set the subject to wear one or the other of the lenses first. They were instructed to wear glasses full time for two weeks. Then, there is a two-week "cleaning" period without wearing research lenses. Subjects then wore different lenses for the next two weeks. Finally, subjects went through a "post-cleaning" period without study lenses and established an exit "complete line" for headache characteristics.

There is a significant amount of variability in the frequency and severity of headaches. In some cases, this variation can also occur in the same patient. Due to the volatility, "pre-clean" and "post-clean" periods have been added. This additional period without study lenses minimized the effect of "baseline drift" in the study subjects.

The HIT-6 questionnaire was administered before and after the study period, resulting in six completed questionnaires for each subject. The study included the first 48 participants, and 33 participants completed the study process. Of the 37 subjects who completed the study, the baseline HIT-6 score was 64.5. Of the 33 subjects, 33 (89%) had a baseline HIT-6 score of 60 or higher. According to the HIT-6 interpretation, these 33 subjects have a headache that is “very seriously affecting” their lives. Both the 480nm and 620nm filter lenses showed a statistically significant reduction in HIT-6 values.

Of the 37 participants who completed the study, 9 subjects wearing 480nm lenses were able to escape the “very serious impact” HIT-6 category; Five subjects wearing 620 nm lenses were able to escape this category; Five subjects wearing either of these lenses could escape this category. 10 subjects experienced a minimum improvement of 6 or more in HIT-6 when wearing a 480nm lens, 10 subjects experienced a minimum improvement of 6 or more in HIT-6 when wearing a 620nm lens, and 3 subjects No matter which lens I was wearing, I experienced an improvement of at least 6 points on the HIT-6. This analysis showed that wearing 480nm or 620nm spectacle lenses reduced HIT-6 statistically significantly. However, when comparing the effects of 480nm and 620nm lenses, there was no significant difference (p = 0.195).

Secondary results collected from the diary, including the percentage of days with severe headaches, the percentage of days when activity should be changed or the subject needs to go to bed, and the percentage of days requiring medication, are primary results for 480nm or 620nm eyeglass lenses It appeared similar to: Subject significantly reduced these parameters when wearing a 480nm or 620nm lens. When comparing the effects of 480nm and 620nm lenses for any of these three results, there was no significant difference.

Melanopsin Melanopsin in ganglion cells is a bistable pigment. Melanopsin can undergo isomerization while exposed to light at certain wavelengths. 27 is a graph 2700 schematically showing the periodic isomerization of a bistable pigment when the pigment is exposed to light of different wavelengths. The bistable pigment can have a first isoform that exhibits a first absorption spectrum 2702. The first absorption spectrum absorbs the first wavelength 2704. The first isoform of the bistable pigment can react with the first wavelength 2704. The first wavelength 2704 can isomerize the bistable pigment and trigger a photoconductive cascade in the associated cell or membrane. In one embodiment, the bistable pigment may be melanopsin, and when exposed to a first wavelength 2704 may trigger a photoconductive cascade in melanopsin ganglion cells. When exposed to the first wavelength, the bistable pigment may be isomerized from the first isomer to the second isomer. The first isoform may be the active 11-cis isoform of melanopsin. The second isoform may be an inactive meta-melanopsin isoform. Isomerization of the active 11-cis isoform can lead to a light conversion cascade.

The second isoform may represent a second absorption spectrum 2706. The second absorption spectrum 2706 can absorb the second wavelength 2708. The second isoform of the bistable pigment can react with the second wavelength 2708. In one embodiment, the first isotype is an active isotype of a bistable pigment, and the second isotype can be an inactive isotype of a bistable pigment. In other embodiments, the first isotype may be an inactive isotype of a bistable pigment, and the second isotype may be an active isotype of a bistable pigment. In another embodiment, the first isotype may be an active isotype of melanopsin and the second isotype may be an inactive isotype of melanopsin.

28 shows a graph 2800 of the active absorption spectrum 2802 and the inactive absorption spectrum 2804 for melanopsin. The active absorption spectrum 2802 and the inactive absorption spectrum 2804 correspond to the active isoform of melanopsin and the inactive isoform of melanopsin, respectively. It should be understood that “active” and “inactive” refer to the physiological activity of the pigment and the ability of the pigment to contribute to the individual's photosensitive response rather than the ability of the pigment to absorb light. The active absorption spectrum 2802 can have a maximum value at about 484 nm, and the inactive absorption spectrum 2804 can have a maximum value at about 587 nm.

The inactive isoform of melanopsin can absorb the wavelength of light according to the inactive absorption spectrum 2804. The light absorbed by the inactive isoform of melanopsin may contribute to the conversion of the active form of the inactive isoform to melanopsin. The active form of melanopsin may contribute to an individual's photosensitive response. In at least one embodiment, the attenuation of light absorbed by the inactive isoform interferes with the isomerization of melanopsin and causes light sensitivity symptoms and / or migraine headaches in some people, such as pain or discomfort in response to light. It may reduce the frequency and / or severity, and may also be effective in the treatment of blepharospasm, post-concussion / TBI syndrome, sleep disorders, and epilepsy.

In addition to controlling the exposure of melanopsin ganglion cells to light at around 480 nm and / or 620 nm, the attenuation of light at the maximum absorption of the inactive absorption spectrum for melanopsin's inactive isoform also relieves symptoms associated with light sensitivity. It can make you improve. For example, an optical filter centered at a wavelength of about 590 nm can attenuate light absorbed by the inactive isoform of melanopsin.

In one embodiment, an improvement may be realized by attenuating light between about 560 nm and about 620 nm. In other embodiments, improvements may be realized by attenuating light between about 570 nm and about 610 nm. In another embodiment, the improvement can be realized by attenuating light using a filter that is substantially centered at a wavelength of 590 nm at a half maximum overall width of about 50 nm.

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

Similar to the 480nm filter and 620nm filter described above, the optical filter capable of attenuating 590nm light may include a high pass filter, a low pass filter, an optical notch filter, or a combination thereof. The optical notch filter may include a plurality of layers of dielectric material, nanoparticles dispersed on the host medium or embedded in the host medium, or combinations thereof. Also, any of the above-mentioned combinations can be used with the dye incorporated into the substrate. For example, creating a short-distance pass or notch filter can include using alternating layers of high and low index materials. Examples of low refractive index dielectric materials include MgF ₂ and SiO ₂ . Examples of high refractive index materials include metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ and Ta ₂ O ₅ and Si ₃ N ₄ . Numerous other suitable materials can be used, including polymer layers.

Similar to the embodiment intended to attenuate the wavelength absorbed by the active isoform of melanopsin and described as described above, an optical filter designed to attenuate the wavelength at about 590 nm can be made according to a similar FOM. The amount of light D received at about 590 nm can be recorded as follows:

[Equation 15]

Where L is the light spectrum (intensity, power, photons / second, etc.), T is the spectral transmission of the filter placed between the light source and the eye, R ₅₉₀ is the ideal response spectrum at about 590 nm, which is half of 50, 55 or 60 nm It can be estimated with a Gaussian function centered on 620 nm at the maximum overall width, but other values may also prove to be expected and therapeutic. In general, it is assumed that L = 1 so as not to limit the discussion of any particular light source, but analysis can be performed on any light source of a known spectrum.

Similar light quantities can be calculated with respect to the visible response spectrum.

[Equation 16]

Here, V represents a standardized visual response spectrum.

The effect of an optical filter, such as a nanoparticle notch filter, is, for example, the ratio of the amount of light calculated by the filter to the amount of light without a filter, for example,

Is to decrease the amount of light as described.

The "attenuation" of the capacity can be described, for example, as follows:

A FOM can also be defined comparing light blocking at about 590 nm and blocking of the visible response spectrum.

[Equation 17]

This represents the ratio of the attenuation of light at about 590 nm to the attenuation of light across the visible spectrum, where a value of FOM> 1 may be desirable. Using the method described above to estimate the visual response at about 590 nm, the comparison becomes more stringent when a smaller overall width half maximum value is used. For example, if the Gaussian distribution R (λ) used for estimation has a total width of half up to 50 nm, a more specific optical filter is created than if the estimation includes R (λ) having a maximum value of half full width of 60 nm. Pay.

29 shows a method 2900 for reducing symptoms associated with a photosensitive reaction. Method 2900 includes receiving 2902 light, attenuating the first wavelength (2904), and optionally attenuating the second wavelength (2906). Attenuation of the first wavelength may then stop the bistable pigment cycle described in connection with FIG. 27 (2908). In one embodiment, the first wavelength may be determined by a maximum active absorption spectrum or an inactive absorption spectrum of a bistable pigment. In other embodiments, the first wavelength may be determined by the maximum active absorption spectrum 2802 of melanopsin or the maximum inactive absorption spectrum 2804 described with respect to FIG. 28. In another embodiment, the first wavelength may be 480 nm, and in a further embodiment, the first wavelength may be 590 nm.

It should be understood that attenuating the wavelength means preferentially attenuating the wavelength or range including the wavelength compared to other parts of the visible spectrum. For example, attenuating the 590 nm wavelength may include transmitting less light at 590 nm wavelength or at about 590 nm wavelength than other light in the visible spectrum. In another example, attenuating the 590 nm wavelength may include blocking substantially all light at or near the 590 nm wavelength and transmitting other light in the visible spectrum.

Attenuating the second wavelength 2906 may include attenuating a portion of the second wavelength that is different from the attenuated first wavelength. In one embodiment, the second wavelength may be determined by a maximum active absorption spectrum or an inactive absorption spectrum of a bistable pigment. In other embodiments, the first wavelength may be determined by the active absorption spectrum 2802 of the maximum melanopsin described in connection with FIG. 28 or the inactive absorption spectrum 2804 of the maximum melanopsin. In another embodiment, the first wavelength may be 480 nm, and in a further embodiment, the first wavelength may be 590 nm.

Attenuating the first wavelength 2904, and optionally attenuating the second wavelength 2906, can interfere with the bistable pigment cycle. Attenuating the first wavelength 2904 can suppress isomerization of the bistable dye from the first isomer to the second isomer. The first isoform can be an active isotype or an inactive isotype. By attenuating the second wavelength 2906, isomerization of the bistable dye from the second isoform to the first isoform can be suppressed.

An optical filter capable of attenuating light at a wavelength of about 590 nm or at a wavelength of about 590 nm is manufactured and / or tuned by any of the processes described above such that a low pass filter, high pass filter or optical notch filter preferentially attenuates 590 nm light. Can be. Filters can include dielectric multilayers, embedded nanoparticle coatings, color filters, tints, resonant induction mode filters, lugate filters, and any combination thereof. The filter may also include embedded nanoparticle coatings such as metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material and a cell material acting as a cell in the core.

Because the optical filter of the present disclosure filters certain colors in the visible spectrum, tinting may appear when viewed through the filter. The standard way to quantify this coloration is to use CIE chromaticity diagrams that generally refer to 1931 standard observations, but other versions of the CIE color space can be used (e.g. 1964 10 ° chromaticity coordinates, or based on Stiles & Burch data, etc.) Coordinates, and the results are quite similar), where the two chromaticity coordinates 'x' and 'y' are mapped to human color perception. The CIE chromaticity diagram has a point called a colorless point (x = y = 1/3) where the perceived color is white (or gray depending on the transmitted brightness or luminance level Y). Ideally, the optical filter for observation may have chromaticity coordinates x = y = 1/3.

Calculation of chromaticity coordinates is achieved through a color matching function (CMF) based on physiological response to light of different wavelengths. Again, CMF generally refers to 1931 2 ° data, but other CMFs can be used (e.g. 1964 10 ° color matching function or CMF based on Stiles & Burch data) and the results are quite similar. The following functions can be used as weighting factors for the input spectrum:

[Equation 18]

[Equation 19]

[Equation 20]

X, Y and Z are known as tristimulus values, L is the light spectrum (intensity, power, photons / sec, etc.), T is the spectral transmittance of the filter between the light source and the human eye, X, Y and Z is a color matching function. The 1931 CMF is shown in Figure 30. L can be a standard light source such as D50 or D65 during the day, or it can represent the spectrum of certain artificial light sources such as incandescent (A), fluorescent (series F), LED (series L), etc., but L = 1 without loss of generality (eg For example, it can be assumed that it is the fixture E), and any valid function L may be used.

The chromaticity coordinates can be calculated from the following tristimulus values:

Only x and y are needed.

,

및

와 함께, 본 개시에 따른 480nm 노치 필터를 도시한다. 이 필터의 삼자극 값은 X = 94.8, Y = 92.4 및 Z = 58.4이며, 해당 색도 좌표는 x = 0.386 및 y = 0.376이다. 색도 다이어그램을 기반으로, 이것은 황색에 매핑되며, 필터가 황색 색조로 일반 색상을 수정하는 것을 의미한다.As an example, FIG. 31 is a product representing a color matching function as modified by the presence of a filter.

,

And

Together, a 480 nm notch filter according to the present disclosure is shown. The tristimulus values for this filter are X = 94.8, Y = 92.4 and Z = 58.4, and the corresponding chromaticity coordinates are x = 0.386 and y = 0.376. Based on the chromaticity diagram, this maps to yellow, meaning that the filter modifies the normal color with a yellow tint.

By adding a second notch at a wavelength around 590 nm, the chromaticity coordinates of the filter can be adjusted towards the achromatic point, thus rendering the filter gray. One such embodiment is shown in FIG. 32, in which case the 480 nm and 590 nm notches reduce the overall transmittance, but reduce the overall transmittance but the Gaussian functions (center wavelengths 480 nm and 590 nm, half maximum overall width 31 nm and 50 nm, notch depth 0.625 and 0.41; respectively) Approximated to a total reduction of 10% over the visible spectrum to give a light gray tint that has no effect).

The 480 nm notch alone again has tristimulus values X = 91.8, Y = 89.9 and Z = 68.5 at chromaticity coordinates x = 0.367 and y = 0.359, which produces a yellowish hue. The addition of the 590 nm notch achieves almost the same achromatic condition by making the tristimulus values almost the same with X = 68.1, Y = 68.4 and Z = 68.2 at chromaticity coordinates x = 0.3327 and y = 0.3341.

A number of different combinations are possible based on adjusting the width, depth, shape and position of the two notches. For example, since blocking light near 480nm and 590nm wavelengths is known to reduce light sensitivity and migraine, one filter design procedure first (i.e., melanopsin action potential spectrum R _melan or a constant amount over a wavelength range Design a therapeutic 480 nm notch (designed to achieve a specific FOM, as disclosed by the present invention, or to achieve blocking), and then add a second notch at about 590 nm to achieve the desired achromatic condition. Again, using a simplified Gaussian notch filter at the center of the half maximum overall width 52 nm and depth 0.625 to 480 nm achieves chromaticity coordinates x = 0.3332 and y = 0.338 using color balance notches at 584 nm center, 51 nm width and 0.57 depth. Can be.

In another embodiment, color balancing notches at about 587 nm, width 67 nm and depth 0.47 can be used to achieve x = 0.3323 and y = 0.3340. First designing a 590 nm therapeutic notch (ie, designed to achieve a certain amount of blocking or to achieve a specific FOM over the R ₅₉₀ response function or wavelength range, as taught by the present invention); Design notches at 480 nm and 590 nm; Adjusting the width and depth to achieve a certain amount of cumulative light blocking that blocks across both R _melan and R ₅₉₀ response functions while simultaneously approaching the desired achromatic conditions, or achieving a specific FOM that considers blocking inside and outside these areas. Includes.

As used herein, the terms "approximately", "about", "nearly" and "substantially" refer to amounts close to the stated amounts that still perform the desired function or achieve the desired result. For example, the terms “approximately”, “about” and “substantially” refer to amounts less than 10%, less than 5%, less than 1%, less than 0.1%, less than 0.01% of the stated amounts.

Although the present invention has been described in connection with the above-described embodiments, these descriptions are not intended to limit the scope of the invention to the specific forms presented, and on the contrary, these descriptions include such alternatives, modifications and equivalents that may be included within the scope of the invention. It is intended to. Any element of the above-described embodiment can be combined with any other element of the above-described embodiment. For example, any of the manufacturing methods or light attenuation methods described above can be combined with the described optical filters and associated wavelengths. Accordingly, the scope of the invention fully encompasses other embodiments that may be apparent to those skilled in the art, and the scope of the invention is limited only by the appended claims.

Claims (28)

A device for reducing the frequency and / or severity of photosensitive hypersensitivity reactions, including migraine, by controlling light exposure to melanopsin ganglion cells of the retina, relative to the visible spectral range from 400 nm to 700 nm, the device comprising:
Light transmittance less than Tmelan as an average over a wavelength between about 454 nm and about 506 nm;
Light transmittance greater than Tvis1 as the average over a wavelength in the visible spectrum of less than about 454 nm; And
Light transmittance greater than Tvis2 as the average over a wavelength in the visible spectrum greater than about 506 nm
It comprises an optical filter consisting of,
The ratio including the light transmittance is defined as a performance index (FOM), which is determined by:

And the performance index of the optical filter is at least 1.6. The optical filter of claim 1, wherein:
Board;
A first layer disposed on the substrate and comprising a high refractive index material; And
And a second layer disposed adjacent the first layer and comprising a low refractive index material. The device of claim 1, wherein the optical filter comprises a dielectric multilayer, embedded nanoparticle coating, resonant induction mode filter or a rugate filter. The apparatus of claim 1, wherein the optical filter comprises one or more color filters or tints. The apparatus of claim 1, wherein the performance index of the optical filter is at least 1.8. The apparatus of claim 1, wherein the performance index of the optical filter is at least 2.0. The apparatus of claim 1, wherein the performance index of the optical filter is at least 2.5. The apparatus of claim 1, wherein the performance index of the optical filter is at least 3.0. A device for reducing the frequency and / or severity of photosensitive hypersensitivity reactions, including migraine, by controlling light exposure to melanopsin ganglion cells of the retina, relative to the visible spectral range from 400 nm to 700 nm, the device comprising:
Light transmittance less than T _{rec, 590} as an average over a wavelength between about 565 nm and about 615 nm;
Light transmittance greater than Tvis1 as an average over a wavelength in the visible spectrum of less than about 565 nm; And
Light transmittance greater than Tvis2 as the average over a wavelength in the visible spectrum greater than about 615 nm
It comprises an optical filter consisting of,
The ratio including the light transmittance is defined as a performance index (FOM), which is determined by:

And the performance index of the optical filter is at least 1.3. The optical filter of claim 9, wherein the optical filter transmits about 45% of the light averaged over a wavelength between 565 nm and 615 nm and about 60% of the light averaged over a wavelength within the visible spectrum of less than 565 nm and greater than 615 nm. Device configured to let. 10. The device of claim 9, wherein the performance index of the optical filter is greater than about 1.5, greater than about 1.8, greater than about 2.75, greater than about 3, or greater than about 3.3. 10. The device of claim 9, wherein the optical filter comprises a dielectric multilayer, embedded nanoparticle coating, color filter, tint, resonance induction mode filter, lugate filter, or any combination thereof. A device for reducing the frequency and / or severity of photosensitive hypersensitivity reactions, including migraine, by controlling light exposure to melanopsin ganglion cells of the retina, relative to the visible spectral range from 400 nm to 700 nm, the device comprising:
Light transmittance less than Tmelan as an average over a wavelength between about 454 nm and about 506 nm;
A light transmittance greater than T _{rec, 590} with an average value over a wavelength between about 565 nm and about 615 nm;
A light transmittance greater than Tvis1 as an average over a wavelength in the visible spectrum less than about 454 nm;
A light transmittance greater than Tvis2 as an average over a wavelength in the visible spectrum greater than about 506 nm and less than about 565 nm; And
Light transmittance greater than Tvis2 as the average over a wavelength in the visible spectrum greater than about 615 nm,
It comprises an optical filter consisting of,
The ratio including the light transmittance is defined as a performance index (FOM), which is determined by:

And the performance index of the optical filter is at least 1.3. The apparatus of claim 13, wherein the performance index of the optical filter is greater than about 1.5, greater than about 1.8, greater than about 2.75, greater than about 3, or greater than about 3.3. The apparatus of claim 13, wherein the optical filter comprises a dielectric multilayer, embedded nanoparticle coating, color filter, tint, resonance induction mode filter, lugate filter, or any combination thereof. A therapeutic treatment method that reduces the frequency and / or severity of photosensitive hypersensitivity reactions, including migraine, by controlling light exposure of cells in the retina, relative to the visible spectral range of 400 nm to 700 nm, the method comprising:
Determining one or more optical wavelength ranges that cause a photosensitive response to the patient, wherein the optical wavelength range is comprised of about 454 nm to about 506 nm, about 565 nm to about 615 nm, about 595 nm to about 645 nm Selected from the group-;
Providing an apparatus having an optical filter configured to transmit a first light amount within the determined light wavelength range D _rec and a second light amount across the remaining visible spectral range D _vis -the optical filter is as follows: With a defined performance index (FOM):

Here, D _rec (T = 1) is light over the determined wavelength range when there is no optical filter, D _vis (T = 1) is light over the remaining visible spectrum when there is no optical filter, and the optical filter The performance index of is at least 1.3; And
Controlling the light exposure of the cells in the retina using the device
How to include. 17. The method of claim 16, wherein providing the device comprises applying the optical filter to one or more lenses of a pair of eyeglasses. 17. The method of claim 16, wherein controlling light exposure using the device comprises wearing the device to the patient. 17. The method of claim 16, wherein providing the device comprises applying the optical filter to one or more windows, computer screens or bulbs. 17. The method of claim 16, wherein the optical filter has a performance index of at least 1.6. A device for reducing the frequency and / or severity of photosensitive hypersensitivity reactions, including migraine, by controlling light exposure to melanopsin ganglion cells of the retina, relative to the visible spectral range from 400 nm to 700 nm, the device comprising:
Light transmittance less than Tmelan as an average over a wavelength between about 454 nm and about 506 nm;
A light transmittance greater than T _{rec, 590} with an average value over a wavelength between about 565 nm and about 615 nm;
A light transmittance greater than Tvis1 as an average over a wavelength in the visible spectrum less than about 454 nm;
A light transmittance greater than Tvis2 as an average over a wavelength in the visible spectrum greater than about 506 nm and less than about 565 nm; And
Light transmittance greater than Tvis2 as the average over a wavelength in the visible spectrum greater than about 615 nm,
It comprises an optical filter consisting of,
The ratio including the light transmittance is defined as a performance index (FOM), which is determined by:

FOM ₁ is at least 1.3 and FOM ₂ is at least 1.1,
The chromaticity coordinates of the optical filter are in the range of x = 0.33 ± 0.02 and y = 0.33 ± 0.02. 22. The apparatus of claim 21, wherein the chromaticity coordinates of the optical filter are x = 0.386 and y = 0.376. 22. The apparatus of claim 21, wherein the chromaticity coordinates of the optical filter are x = 0.3327 and y = 0.3341. 22. The apparatus of claim 21, wherein the chromaticity coordinates of the optical filter are x = 0.3332 and y = 0.338. 22. The apparatus of claim 21, wherein the chromaticity coordinates of the optical filter are x = 0.3323 and y = 0.3340. 22. The apparatus of claim 21, wherein the performance index FOM ₁ of the optical filter is at least 1.4 and the performance index FOM ₂ is at least 1.1. 22. The apparatus of claim 21, wherein the performance index FOM ₁ of the optical filter is at least 1.5 and the performance index FOM ₂ is at least 1.2. 22. The apparatus of claim 21, wherein the performance index FOM ₁ of the optical filter is at least 1.6 and the performance index FOM ₂ is at least 1.2.

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