WO2012177296A1 - Apparatus and methods for reducing frequency or severity of photophobic responses or modulating circadian cycles - Google Patents

Apparatus and methods for reducing frequency or severity of photophobic responses or modulating circadian cycles Download PDF

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WO2012177296A1
WO2012177296A1 PCT/US2012/021500 US2012021500W WO2012177296A1 WO 2012177296 A1 WO2012177296 A1 WO 2012177296A1 US 2012021500 W US2012021500 W US 2012021500W WO 2012177296 A1 WO2012177296 A1 WO 2012177296A1
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light
amount
action potential
apparatus
melanopsin
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PCT/US2012/021500
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French (fr)
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Steven M. Blair
Bradley Jay KATZ
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University Of Utah Research Foundation
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Priority to US61/433,344 priority
Application filed by University Of Utah Research Foundation filed Critical University Of Utah Research Foundation
Publication of WO2012177296A1 publication Critical patent/WO2012177296A1/en
Priority claimed from US14/338,182 external-priority patent/US9764157B2/en
Priority claimed from US15/673,264 external-priority patent/US20170336545A1/en

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    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS, OR APPARATUS
    • G02B5/00Optical elements other than lenses
    • G02B5/20Filters
    • G02B5/28Interference filters
    • G02B5/285Interference filters comprising deposited thin solid films
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M21/00Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis
    • A61M21/02Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis for inducing sleep or relaxation, e.g. by direct nerve stimulation, hypnosis, analgesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • A61N5/0618Psychological treatment
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS, OR APPARATUS
    • G02B5/00Optical elements other than lenses
    • G02B5/20Filters
    • G02B5/22Absorbing filters
    • GPHYSICS
    • G02OPTICS
    • G02CSPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
    • G02C7/00Optical parts
    • G02C7/10Filters, e.g. for facilitating adaptation of the eyes to the dark; Sunglasses
    • G02C7/104Filters, e.g. for facilitating adaptation of the eyes to the dark; Sunglasses having spectral characteristics for purposes other than sun-protection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M21/00Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis
    • A61M2021/0005Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis by the use of a particular sense, or stimulus
    • A61M2021/0044Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis by the use of a particular sense, or stimulus by the sight sense
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/0658Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662Visible light
    • A61N2005/0663Coloured light
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/0664Details
    • A61N2005/0667Filters

Abstract

The present disclosure describes systems, methods, and apparatus for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles by controlling light exposure to melanopsin ganglion cells in a retina over the action potential spectrum of the melanopsin cells of the human eye and a visual spectral response of the human eye. Embodiments of an optical filter are described. In one embodiment an optical filter may be configured to transmit less than a first amount of light weighted across the action potential spectrum of the melanopsin cells and to transmit more than a second amount of light weighted across the visual spectral response. Methods of manufacturing optical filters are also described.

Description

APPARATUS AND METHODS FOR REDUCING FREQUENCY OR SEVERITY OF PHOTOPHOBIC

RESPONSES OR MODULATING ORCADIAN CYCLES

5 CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of and priority to U.S Provisional Patent Application Ser. No. 61/433,344, filed on January 17, 2011, the entirety of which is incorporated herein by reference.

10 BACKGROUND OF THE DISCLOSURE

1. The Field of the Invention

Photophobia, or light sensitivity, describes an adverse response to light that characterizes several neurologic conditions. The present invention relates to managing the effects of light on a subject. More particularly, the present invention 5 relates to methods, systems, and apparatus for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles.

2. The Relevant Technology

The retina of the eye contains various photoreceptor cells. These photoreceptor cells include rods (which are involved in black-and-white and low 0 light vision), cones (which are involved in daytime vision and color perception), and melanopsin ganglion cells.

The melanopsin ganglion cells are photosensitive. This photosensitivity can transmit pain through the pain pathways of the brain. These pathways are further described by Noseda et al. in A Neural Mechanism for Exacerbation of Headache by 5 Light Nat Neurosci. 2010 Feb;13(2):239-45 PMID 20062053, which is hereby incorporated by reference in its entirety. It has been demonstrated previously that modulating ambient light through the use of spectacle tints can be effective in the treatment of light-sensitive neurological conditions including migraine and benign essential blepharospasm. A description of these beneficial effects may be found in 0 Good et al. The Use of Tinted Glasses in Childhood Migraine Headache. 1991 Sep;31(8):533-6 PMID 1960058 and Blackburn et al. FL-41 Tint Improves Blink Frequency Light Sensitivity and Functional Limitations in Patients with Benign Essential Blepharospasm Ophthalmology. 2009 May; 1 16(5):997- 1001 PMID 19410958, which are both hereby incorporated by reference in their entirety In addition to pain pathways, melanopsin ganglion cells also connect to the suprachiasmatic nucleus, where they participate in entrainment of circadian rhythms. These connections are further described by Hannibal J. Roles of PACAP-containing retinal ganglion cells in circadian timing. Int Rev Cytol. 2006;251 : 1-39. Review. PubMed PMID: 16939776, which is hereby incorporated by reference in its entirety.

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

Therefore, it would be desirable to manage the effects of light on a subject. More particularly, it would be desirable to provide methods, systems, and apparatus for reducing the frequency and/or severity of photophobic responses. It would be also desirable to provide methods, systems, and apparatus for modulating circadian cycles.

BRIEF SUMMARY OF THE INVENTION

As the melanopsin ganglion cells are associated with the pain pathways in humans, managing the painful effects caused by certain types of light would be desirable. For example, stimulation of the melanopsin ganglion cells affects the frequency and/or severity of photophobic responses. These photophobic responses include migraine headache, light sensitivity associated with traumatic brain injury, and light sensitivity associated with benign essential blephoraspasm. The melanopsin ganglion cells are also associated with circadian cycles. Thus, methods, systems, and apparatus for reducing the frequency and/or severity of photophobic responses and/or for modulating circadian cycles by controlling light exposure to melanopsin ganglion cells are provided.

An embodiment of an apparatus for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles is described. The apparatus includes an optical filter configured to transmit less than a first amount of light weighted across the action potential spectrum of the melanopsin ganglion cells and to transmit more than a second amount of light weighted across the visual spectral response.

In some embodiments, the first amount of light is about 50% of the light weighted across the action potential spectrum of the melanopsin ganglion cells and the second amount of light is about 75% or greater of the light weighted across the visual spectral response. The first amount of light, in other embodiments, is about 25% of the light weighted across the action potential spectrum of the melanopsin ganglion cells and the second amount of light is about 60% or greater of the light weighted across the visual spectral response. In further embodiments, the first amount of light is approximately all of the light weighted across the action potential spectrum of the melanopsin ganglion cells. The second amount of light, in still further embodiments, is approximately all of the light outside of the action potential spectrum of the melanopsin ganglion cells, weighted across the visual response spectrum. In yet further embodiments, a ratio of the attenuation of the first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells and the attenuation of the second amount of the light weighted across the visual spectral response is more than one.

The first amount of light, in some embodiments, is substantially all light below a long pass filter wavelength within the action potential spectrum of the melanopsin ganglion cells and the second amount of light is all light across the visual spectral response with a wavelength above the long pass filter wavelength. In further embodiments, the long pass filter wavelength is 500nm. The action potential spectrum of the melanopsin ganglion cells, in still further embodiments, is between about 454nm and about 506nm. In some embodiments, the second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells. The second amount of light, in other embodiments, includes a third amount of light having a wavelength that is greater than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells. In further embodiments, the second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and a fourth amount of light that is greater than the maximum relative response of the action potential spectrum of melanopsin. The second amount of light, in still further embodiments, includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is lower than a relative response at a standard deviation of the action potential spectrum of melanopsin. In yet further embodiments, the second amount of light includes a third amount of light having a wavelength that is greater than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is greater than a relative response at a standard deviation of the action potential spectrum of melanopsin. The second amount of light, in even further embodiments, includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is lower than a relative response at a standard deviation of the action potential spectrum of melanopsin and a fourth amount of light having a wavelength that is greater than the maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is greater than the relative response at the standard deviation of the action potential spectrum of the melanopsin ganglion cells.

The second amount of light, in some embodiments, includes at least one wavelength that is less than about 480nm. In further embodiments, the second amount of light includes at least one wavelength that is more than about 480nm. The second amount of light, in still further embodiments, includes at least one wavelength that is less than about 480nm and at least one wavelength that is more than about 480nm. In some embodiments, the first amount of light is a dose of light experienced by the melanopsin ganglion cells of a subject (Dmeian) and the second amount of light is a dose of light experienced over the visual response spectrum (Dvjs), and wherein a ratio including the first amount of light and the second amount of light is defined as a figure of merit (FOM), the figure of merit being determined by:

Figure imgf000006_0001

wh is the first amount of light in the absence of an optical filter, and

Figure imgf000006_0002
second amount of light in the absence of an optical filter. The figure of merit of the optical filter, in some embodiments, may include about one, more than about one, more than about 1.3, more than about 1.5, more than about 1.8, more than about 2.75, more than about 3, more than about 3.3. Other figures of merit may be used in other embodiments.

In some embodiments, the first amount of light defines a spectral width that has a median at a median of the action potential spectrum of the melanopsin ganglion cells. The first amount of light and the second amount of light, in further embodiments, are determined based on the characteristics of ambient light. In still further embodiments, the first amount of light and the second amount of light are selectively adjustable by way of a transition type coating.

The optical filter, in some embodiments, includes at least one layer configured to minimize or reduce the effect of an angle of incidence of the received light. In further embodiments, the optical filter further comprises a substrate that includes a tint by impregnation or by coating.

In some embodiments, the optical filter is further configured to attenuate a third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells. The third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells, in further embodiments, is less than about 50%. In still further embdoients, the third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells is less than about 25%. The third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells, in yet further embodiments, is less than about 10%. In even further embodiments, the optical filter is further configured to attenuate more than a fourth amount of back reflected light weighted across the visual spectral response.

The fourth amount of back reflected light weighted across the visual spectral response, in some embodiments, is less than about 50%. In further embodiments, the fourth amount of back reflected light weighted across the visual spectral response is less than about 25%. The fourth amount of back reflected light weighted across the visual spectral response, in still further embodiments, is less than about 10%.

An embodiment of a system for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles is described. The system includes a substrate, a first layer disposed on the substrate, and a second layer disposed adjacent the first layer. The first layer includes a high index material. The second layer includes a low index material.

In some embodiments, the substrate has a front surface and a back surface, wherein the first layer and the second layer are disposed on the front surface. The substrate, in further embodiments, is tinted.

The high index material, in some embodiments, includes Ti02. In further embodiments, the thickness of the first layer is 165nm. The low index material, in still further embodiments, includes SiC>2. In yet further embodiments, the low index material includes MgF2. A thickness of the first layer, in even further embodiments, is 40nm.

In some embodiments, the high index material of the first layer is Ti02 and the low index material of the second layer is Si02 and further comprising one or more additional alternating adjacent layers of Ti02 and Si02, wherein the first additional layer is adjacent the second layer and wherein the last additional layer may be MgF2, Si02 or Ti02 and is adjacent the outer layer. In further embodiments, the system may include additional layers and/or types of material, wherein the materials cooperate to transmit less than a first amount of light weighted across the action potential spectrum of the melanopsin ganglion cells and to transmit more than a second amount of light weighted across the visual spectral response. In some embodiments, increasing the number of layers in the optical filter increases transmission of light outside the action potential spectrum. The optical filter, in some embodiments, is a notch filter that comprises 10 dielectric layers, the notch filter being configured to block about 61% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 21% attenuation weighted across the visual spectral response. In further embodiments, wherein the notch filter comprises 15 dielectric layers, the notch filter being configured to block about 70% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 25% attenuation weighted across the visual spectral response. The notch filter, in still further embodiments, includes 19 dielectric layers, the notch filter being configured to block about 89% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 29% attenuation weighted across the visual spectral response. In yet further embodiments, the substrate further comprises a first side, and wherein the first layer is applied to the first side, and wherein an anti-reflection coating is applied to a side of the substrate opposite the first side.

An embodiment of a method of manufacturing an optical filter for reducing the frequency and/or severity of photophobic responses is described. The method includes determining an appropriate light spectrum. A first light dose to be experienced by the melanopsin ganglion cells in the subject is determined. A second light dose associated with the visual response spectrum is determined. An optical filter is manufactured using the first light dose and the second light dose.

In some embodiments, an action potential spectrum of an individual's melanopsin ganglion cells is determined. The optical filter, in further embodiments, is configured to attenuate the first amount of light based on the individual's melanopsin ganglion cells. In still further embodiments, the optical filter is manufactured based on visual response spectrum characteristics.

The optical filter, in some embodiments, is a notch filter. In further embodiments, the notch filter is configured to block light that strikes at a non- normal incidence angle. The notch filter, in still further embodiments, includes a filter optimized for a plurality of tilted incidence angles. In yet further embodiments, the notch filter is designed with a slight red shift. The notch filter, in even further embodiments, includes a filter notch that attenuates light across a spectral width. In some embodiments, manufacturing of the optical filter includes widening the filter notch to increase attenuation of the effective melanopsin action potential spectrum. Manufacturing of the optical filter, in further embodiments, includes deepening the filter notch to increase attenuation of the effective melanopsin action potential spectrum. In still further embodiments, manufacturing of the optical filter includes widening the filter notch and deepening the filter notch to increase attenuation of the effective melanopsin action potential spectrum. Manufacturing of the optical filter, in yet further embodiments, includes material deposition that incorporates target-source geometry modification.

In some embodiments, manufacturing of the optical filter includes using dielectric multi-layers, embedded nanoparticle coatings, a color filter, tint, resonant guided-mode filter, a rugate filter, and any combination thereof. The embedded nanoparticle coatings, in further embodiments, include at least one of metallic nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in a core and a shell material serving as a shell. In still further embodiments, the at least metallic nanoparticles include at least one of Al, Ag, Au, CU, Ni, Pt, or other metallic nanoparticles, wherein the dielectric nanoparticles include at least one of Ti02, Ta205, or other dielectric nanoparticles. The semiconductor nanoparticles or quantum dots, in yet further embodiments, include at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles. In even further embodiments, a shape of the embedded nanoparticles in the embedded nanoparticle coatings is spherical, elliptical, or otherwise shaped. In some embodiments, an extinction spectrum of the embedded nanoparticles is determined using Mie scattering theory.

In further embodiments, a third light dose of back reflected light to be experienced by the melanopsin ganglion cells in the subject is determined. A fourth light dose of back reflected light associated with the visual response spectrum, in still further embodiments, is determined. In yet further embodiments, manufacturing an optical filter includes using the third light dose and the fourth light dose.

An embodiment of a method for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles is described. The method includes receiving an amount of light. Less than a first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells is transmitted. A second amount of the light weighted across the visual spectral response is transmitted.

An embodiment of a system for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles is described. The system includes a light source and an apparatus as described herein.

An embodiment of a method for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles is described. The method includes receiving an amount of light from a light source. Less than a first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells is transmitted. A second amount of the light weighted across the visual spectral response is transmitted.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The drawings constitute a part of this specification and include exemplary embodiments of the invention, which may be embodied in various forms. It is to be understood that in some instances various aspects of the invention may be shown exaggerated or enlarged to facilitate an understanding of the invention.

FIG. 1 illustrates an exemplary measured action potential spectrum for melanopsin cells, which is normalized to unity magnitude, with a Gaussian fit to the measured data points.

FIG. 2 illustrates the measured transmission spectrum of an exemplary "FL- 41 35" filter across the "effective action potential spectrum" of melanopsin.

FIG. 3 illustrates the measured transmission spectrum of an exemplary "FL- 41 35" filter across the visible light spectrum.

FIG. 4 illustrates the measured transmission spectrum of an exemplary "FL- 41 55" filter across the "effective action potential spectrum" of melanopsin.

FIG. 5 illustrates the measured transmission spectrum of an exemplary "FL- 41 55" filter across the visible light spectrum.

FIG. 6 is an example of a filter using multi-layer dielectric thin films of distinct refractive indices.

FIG. 7 is an example of a filter using an embedded nanoparticle coating designed to scatter light in the aqua region of the visible light spectrum. FIG. 8 illustrates an exemplary method for designing an optical filter to block light absorption by melanopsin cells

FIG. 9 illustrates the measured transmission spectrum of one embodiment of a filter across the "effective action potential spectrum" of melanopsin.

FIG. 10 illustrates the measured transmission spectrum of the embodiment of a filter in FIG. 9 across the visible light spectrum.

FIG. 11 illustrates the measured transmission spectrum of another embodiment of a filter across the "effective action potential spectrum" of melanopsin.

FIG. 12 illustrates the measured transmission spectrum of a further embodiment of a filter across the "effective action potential spectrum" of melanopsin.

FIG. 13 illustrates the measured transmission spectrum of a still further embodiment of a filter across the "effective action potential spectrum" of melanopsin.

FIG. 14 illustrates the measured transmission spectrum of the embodiment of a filter in FIG. 13 across the visible light spectrum.

FIG. 15 illustrates the measured transmission spectrum of an even further embodiment of a filter with the center of the filter positioned at 485nm for normal light incidence across the "effective action potential spectrum" of melanopsin.

FIG. 16 illustrates the measured transmission spectrum of the embodiment in FIG. 15 with an incidence angle of 15 degrees across the "effective action potential spectrum" of melanopsin.

FIG. 17 illustrates the measured transmission spectrum of a yet further embodiment of a filter excluding a low-index MgF2 layer across the "effective action potential spectrum" of melanopsin.

FIG. 18 illustrates the measured transmission spectrum of an embodiment of a filter centered at 482.9nm with a width of about 55.5nm.

FIG. 19 illustrates the measured transmission spectrum of multiple embodiments of filters with varying degrees of tint.

FIG. 20 illustrates the backside reflection spectra of the embodiments of filters in FIG. 19. FIG. 21 illustrates an exemplary embodiment of a method of manufacturing an optical filter.

FIG. 22 illustrates an exemplary embodiment of a method for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Detailed descriptions of embodiments of the invention are provided herein. It is to be understood, however, that the present invention may be embodied in various forms. Therefore, the specific details disclosed herein are not to be interpreted as limiting, but rather as a representative basis for teaching one skilled in the art how to employ the present invention in virtually any detailed system, structure, or manner.

The present invention relates to managing the effects of light on a subject. Some applications of the present invention relate to methods, systems, and apparatus for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles.

Because the melanopsin ganglion cells have been implicated in photophobia and in the onset of migraines in a number of photophobic subjects, it is desirable to block at least portions of that part of the visible spectrum that activates these cells. Photophobia is associated with light-sensitive neurological conditions, including migraine headaches, benign essential blepharospasm and traumatic brain injury (TBI). FIG. 1 illustrates an example of the measured action potential spectrum for melanopsin cells, which is normalized to unity magnitude, and a Gaussian fit to the measured data points. This Gaussian fit may be used in at least one embodiment of a filter design, but this should not be interpreted as the spectral basis for optimal filters, as more refined measurements of the action potential spectrum may become available. These refined measurements may motivate additional filter designs or methods following the process described here, or via similar processes. Optimizations of the methods, systems, and apparatus described herein based on more refined measurements of the action potential spectrum are contemplated.

In some embodiments, light may be blocked (i.e. attenuated) over a certain wavelength range appropriate for photophobia prevention, while minimizing the distortion of the visible spectrum. In other embodiments, the methods, systems, and apparatus described in this application may also be used to manipulate the body's circadian system.

Embodiments of optical filters are described that block a certain part of the optical spectrum that is suspected to trigger and/or exacerbate these photophobic responses. These filters can be applied to eyewear (such as spectacles, goggles, clip- ons, or other eyewear), lenses (including contact lenses), computer screens, windows, car windshields, lighting substrates, light bulbs (incandescent, fluorescent, CFL, LED, gas vapor, etc), or any other optical element. These optical filters may be applied to crown glasses (including BK7), flint glasses (including BaFs), Si02, plastics (such as polycarbonate, CR-39, and trivex), other substrates, and combinations thereof.

Although the majority of the description focuses on photophobia prevention, the systems, methods, and apparatus described herein are also applicable to modulating circadian rhythm. For example, these filters could be used for manipulation of the body's circadian system by business people, athletes, others who travel between different time zones, or those who desire to manipulate the body's circadian system. In one example, a subject would wear at least one of the filters described herein to help them adapt to the light/dark cycle of the locale to which they are traveling. In another example at least one of the filters described herein could also be used to limit excitation of the melanopsin ganglion cells in patients with sleep disorders. In this use, a subject could wear these filters to limit their exposure to artificial light in the evening, and prevent their internal clocks from thinking that it is time to stay awake. In addition, subjects may increase exposure to light before sunrise to adjust their light/dark cycle.

The FL-41 lens tint is sometimes prescribed for migraine patients. The FL- 41 tint blocks (via absorption) a broad range of wavelengths. These wavelengths include wavelengths associated with melanopsin absorption. The FL-41 dye can be infiltrated into certain types of plastic spectacle lenses. The amount of dye infiltrated generally determines the amount of light intensity blocked. The "FL-41 35" tinting is effective for a number of patients in indoor environments. However, if the light source increases in intensity, by for example moving to an outdoor environment, the "FL-41 35" may not be as effective. FIG. 2 shows the measured transmission spectrum of "FL-41 35". FIG. 2 also illustrates the effect of the "FL-41 35" filter on the action potential spectrum of melanopsin, a so-called "effective action potential spectrum." The "FL-41 35" tinting blocks, or attenuates, about 55% of the light that would otherwise be absorbed by the melanopsin ganglion cells. The FL-41 tinting further blocks a significant portion of the visible spectrum that is not associated with melanopsin, as shown in FIG. 3, with about a 47% attenuation across the visual response spectrum. The additional blocking the visible response spectrum may be disadvantageous. For example, blocking the visible response spectrum may adversely affect normal vision. In another example, blocking the visible response spectrum may produce a false coloration that may be distractive or otherwise less desirable for the wearer.

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

Overall, the general drawbacks to FL-41 include: a rose colored appearance, distorted color perception; limited applicability (i.e. it may only be applied to certain plastics and may not be applied to glass lenses, computer screens, windows, car windshields, lighting substrates, light bulbs, or other optical elements); and poor quality control over the tinting process (due in part to variations in the tintable hard coating layers). Although FL-41 may be effective in certain applications, it is not designed to down-regulate the stimulation of the melanopsin ganglion cells and their connections to pain centers in the brain. For these reasons, it may be desirable to develop other embodiments of filters.

One example of a more desirable optical filter for the treatment of light sensitive conditions may include a long-pass filter. A long pass filter may highly transmit wavelengths longer than about 500nm or 520nm, while attenuating light at wavelengths shorter than about 500nm or 520nm. Other examples of more desirable optical filters may include filters that only block the spectrum of light absorbed by melanopsin, while generally transmitting the rest of the light spectrum, with the spectral transmission response of the filter taking the form of a notch, sometimes called a band stop or minus filter. The center position of the notch may be near the absorption maximum of the melanopsin pathway (about 480nm), but other positions may be effective. The spectral width of the notch may approximately match the width of the action potential spectrum, which is about 50 to 60 nm, although other widths are contemplated.

Optical filter technologies such as tints comprised of dye mixtures, dielectric multi-layers (an example of which is shown in FIG. 6), and embedded nanoparticle coatings (an example of which is shown in FIG. 7), other filter technologies such as resonant waveguide filters, or combinations thereof may be used to create a filter according to the present disclosure. Nanoparticle coatings that may be used for optical filters according to the present disclosure may include metallic nanoparticles (e.g. Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g. Ti02, Ta205, etc.), semiconductor nanoparticles or quantum dots (e.g. Si, GaAs, GaN, CdSe, CdS, etc), magnetic nanoparticles, core-shell particles consisting of one material in the core and another serving as a shell, other nanoparticles, or combinations thereof. Shapes of these particles may be spherical, ellipsoidal, otherwise shaped, or combinations thereof. Host materials may 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.

An embodiment of a multi-layer filter 600, shown in FIG. 6, includes a substrate 602, a first layer 604, and a second layer 606. As shown, the first layer 604 may include a high index material and the second layer 606 may include a low index material. In other embodiments, the first layer 604 may include a low index material and the second layer may include a high index material. Additionally, the first layer 604 is shown adjacent the substrate 602. In other embodiments, the first layer 604 may have another layer (for example, second layer 606 and/or another layer) between the substrate 602 and the first layer 604. Additional layers are also shown (though not numbered). The substrate 602 may utilize any substrate described herein. For example, the substrate 602 may include a tinted layer (not shown) on the same and/or opposite side of the first layer 604 and second layer 606 (i.e. the front and/or back side of the substrate). In another example, the substrate 602 itself may be impregnated with tint. Examples of tinting techniques and amounts are described below. Other embodiments of multi-layer filters are further described herein.

A 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 the substrate 702. In other embodiments, the host layer 704 may have another layer (for example, second layer 606 from FIG. 6 and/or another layer) between the substrate 702 and the host layer 704. Although the nanoparticles 706 are shown as spherical and uniformly sized, as described above, other shapes and sizes are contemplated. As with the multi-layer filter of FIG. 6, various substrates, tints, other features, or combinations thereof may be used with the nanoparticle filter 700. Other embodiments of nanoparticle filters are described herein.

Other types of filters that may be used may include color filters (organic dye and semiconductor), resonant guided-mode filters, rugate filters, or combinations thereof. A rugate filter utilizes a sinusoidal refractive index variation throughout its thickness. A true sinusoid may not be obtainable and is often approximated by a staircase refractive index approximation using the mixture of two or more materials.

In addition to these various filter types, further considerations may take into account the effect of the designed filter on the visual response spectrum, as determined by the photoresponse of the rods and cones. One consideration may include minimizing spectral distortion. Adding additional or other constraints on filter design may be considered, including optimization methods, such as taking angular sensitivity into account, which can be compensated for, using dielectric multi-layers, for example, by designing the center of the notch to be slightly red- shifted from about 480nm to account for the blue-shift of the filter response that occurs for off-axis illumination. Optimization may further include widening the filter spectral width to compensate for non-normal incidence angles, and/or through the use of additional filter layers to compensate for angle of incidence. The potential for backside reflection may be a consideration. One or more of these considerations may be addressed by combining the filter with some form of tinting.

One embodiment of a method for manufacturing an optical filter to block light absorption by melanopsin cells is described herewith. The light dose D experienced by melanopsin cells can be written Dmdcm = J L(X)T(X)M(X)d (1) where L is the light spectrum (in terms of intensity, power, photons/sec, etc), T is the spectral transmission of a filter lying between the light source and the eye, and M is the normalized action potential response spectrum of melanopsin, as currently estimated from FIG. 1 as a Gaussian function centered at 480nm with a full-width at half-maximum of 52nm. For generality, it is assumed that L=l so as not to limit discussion to any specific light source, however analyses may be performed for any light source of known spectrum.

A similar dose can be calculated in association with the visual response spectrum

Dvis = j L(X)T(X)V(X)d (2) where V represents the normalized visual response spectrum.

The effect of an optical filter, such as the FL-41 tint, is to reduce the dose, as described by taking the ratio of dose calculated with the filter to dose without the filter, for example

N me/an

melon

^ melon (

The "attenuation" of the dose may be written as, for example,

A = \ - N = 1 - ^melan

melon melon 7-* r -i \

^ melon V ~ V

A figure of merit (FOM) can also be defined which compares the blocking of the melanopsin response to the blocking of the visual response spectrum

Figure imgf000017_0001
which 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 F0M>1 may be desirable. For the FL-41 tint, FOM is about 1.

FIG. 8 illustrates one embodiment of a method 800 for designing an optical filter to block light absorption by melanopsin cells that may include determining the light dose D experienced by melanopsin cells (using, for example, Equation 1), as illustrated by act 802. The light dose experienced across the visual response spectrum may be determined (using, for example, Equation 2), as illustrated by act 804. A figure of merit (FOM) may be determined with respect to the light dose experienced by the melanopsin cells and to the light dose experienced across the visual response spectrum, as illustrated by act 806. In other embodiments, the dose across the visual response spectrum may be reduced or separated. For example, only a portion or portions of the visual response spectrum may be used, or wavelengths outside the visual response spectrum may be considered. The figure of merit may be used to design an optical element to reduce and/or prevent photophobic responses.

Many embodiments described herein use multi-layer dielectric thin films of distinct refractive indices. These layers may be applied to a number of optical elements (as described herein). By way of example, and in no way intended to be limiting, embodiments of optical filter designs of the present disclosure assume a generic transparent substrate, such as a spectacle lens, with refractive index around 1.5, and with an anti-reflection coating applied to the back surface (i.e. the surface closest to the user's eye). Thus, other substrates with other refractive indices, and with or without back surface anti-refection coatings, are contemplated. Minor variations in filter design may be required to compensate for different substrate materials and/or different coatings on those substrates. Further considerations may need to be addressed such as compatibility of different thin-film materials with different substrate materials, which may require further design optimization, and the curvatures of the lens substrate. The substrate may include an adhesion layer (for example a thin layer of chromium) between the substrate, or a layer on the substrate, and any further coatings.

There are a multitude of design approaches to multi-layer long-pass and notch filters which may be used. For example, software and other design tools are available for the design of thin film optical filters. These tools may take a number of constraints into account during optimization, reducing the likelihood that any two filter designs will be identical, even if accomplishing the same light blocking characteristics or producing the same physiological result. Only a few examples will be presented here and are not meant to be limiting in any way. Other approaches could be taken to achieve similar results, and further optimizations could be performed in order to produce more ideal characteristics, or to produce similar characteristics with fewer number of layers, in accordance with the present disclosure.

In addition, multi-layer and other coatings may be applied to tinted lenses or substrates. There are multiple reasons why this combination may be desirable. One reason may include that the spectral characteristics of the tint may relax design constraints on the thin film filter. For example, combining an FL-41 "base tint" with a thin-film notch filter may serve to reduce the depth of the notch necessary to produce a therapeutic outcome. It may be desirable to take into account the spectral variation of transmission of the tint in the notch design. This design adjustment may be accomplished by, for example, shifting the center wavelength of the notch to compensate for the local slope of the tint spectral response. Another reason for using a base tint may be to reduce any undesirable reflection of light that enters though the backside of the lens. In this situation, it may be desirable to use a "flat," or neutral density, tint that would not introduce any coloration in and of itself.

For example, in an embodiment of a filter designed to block a range of wavelengths of light from passing through the front of the lens (by, for example, reflecting the desired wavelengths away from the user), the light entering the back side of the lens (which includes light in the wavelengths to be blocked) may be reflected back into the user's eye. In other words, the light to be blocked from the front (by reflection in the case of a multi-layer filter) may then be reflected from the back. This may not be a concern in situations where there is a single light source that is mainly in front of the subject. However, in situations, for example, where very bright light is found or where there are multiple light sources, this back reflection may be deleterious to the user.

One example approach to producing long pass or notch filters includes using alternating layers of high and low refractive index materials. Example low index dielectric materials include MgF2 and Si02. MgF2 is commonly used in single and multi-layer anti-reflection coatings. Example high index materials include metal oxides such as Ti02, T13O5, Zr02, and Ta205, and S13N4. Numerous other suitable materials can be used, including polymer layers.

One embodiment of an optical filter design is shown in FIGS. 9 and 10, along with the effect of this embodiment of a filter on the spectrum of light that strikes melanopsin cells, producing an effective (and attenuated) action potential. This design is intended to be as clinically effective as the FL-41 35 coating, in that 55% of the light that would be absorbed by melanopsin cells is blocked, or attenuated, which should result in the same alleviation of migraine (or light sensitive) symptoms as the FL-41 coating, but with significantly less visual distortion, with only 18% attenuation across the visual response. For this embodiment, the low index material is Si02 and the high index material Ti02, and MgF2 is used as the outermost layer, and 11 total layers are used. Exemplary layers and materials are listed in the table below from the outermost layer (MgF2) to the innermost layer (Ti02 with 165nm thickness) adjacent to the substrate. This filter has FOM«3.

Figure imgf000020_0001

The spectral position of the center of a notch filter may be determined by the thicknesses of its respective layers. Although many embodiments herein assume the spectral position of the notch is at about 480nm, other spectral positions are contemplated. For example, as more information about the action potential spectrum of the melanopsin pathway is known, the spectral position may be shifted in accordance with the new information. In another example, the spectral position may be otherwise positioned to achieve specific results.

The width of the notch may be determined by the difference in refractive indices of the different layers. The depth of the notch may be determined by the number of layers. The transmission outside of the notch region may be increased and flattened through the inclusion of additional layers, and with the possible inclusion of a single or multi-layer anti-reflection coating applied to the back surface of the lens to reduce backside reflection. Further design optimization can be used to increase the depth of the notch which may further suppress excitation of melanopsin cells, but the effect on the visual response spectrum should be considered. Overall suppression may be tailored on a patient-by-patient basis or by designing one or more general classes of filters in order to help the majority of cases.

Greater attenuation of the effective melanopsin action potential spectrum may be obtained by either deepening or widening the filter notch, or through a combination of both. FIGS. 11 and 12 illustrate embodiments of two exemplary approaches, using 19 and 15 dielectric layers, respectively. The ultimate choice between the two can be made based upon wearer preference, as both produce about a 70% attenuation across the melanopsin spectrum, but have slightly different visual response spectrum characteristics. 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 FOM values greater than 2.75, with the 19 layer filter having an FOM value of about 3.3.

Different designs may achieve significant attenuation across the melanopsin action potential spectrum. FIGS. 13 and 14 show an embodiment of a notch filter design that produces a melanopsin action potential attenuation similar to the FL-41 55 filter, blocking about 89% of the light, using 19 dielectric layers, but blocking only about 29% of the visual response spectrum, with an FOM value of about 3. Exemplary layers and materials are listed in the table below from the outermost layer (MgF2) to the innermost layer (Ti02 with 160.3nm thickness) adjacent to the substrate.

Figure imgf000022_0001

Other design considerations may include blocking for light that strikes at non-normal incidence angles. For instance, tilting the angle of a thin film filter tends to produce a blue-shift in the filter response. This may be accommodated, for example, by either purposefully designing the filter with a slight red shift, by broadening the width of the filter, adding additional layers, or combinations thereof to minimize or reduce the effect of the angle of incidence.

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

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

This embodiment of a filter has the following layer properties listed in the table below from the outermost layer (MgF2) to the innermost layer (Ti02 with 127nm thickness).

Figure imgf000023_0001

In the embodiments of filters described in connection with FIGS. 8-15, a low-index MgF2 layer was used. Other embodiments may not require this material. For example, FIG. 17 illustrates an embodiment of filter design which blocks about 73% of the melanopsin action potential spectrum (or light dose) and about 21% of the dose of the visible response, with an FOM value of about 3.5. The layer properties of the filter design illustrated in FIG. 17 are listed in the table below from the outermost layer to the innermost layer.

Figure imgf000024_0001

As discussed above, it may be desirable to reduce the amount of light that is reflected from the back side (i.e. the side closest to the user's eye) into the user's eye. This may be accomplished by another embodiment of a filter design in which a thin film coating may be applied onto a tinted lens or substrate, in other embodiments, the substrate may be tinted by impregnation, coating, other tinting techniques, or combinations thereof. The transmission of light through a thin-film coating / tinted substrate combination may be written as the product of the transmission of the thin-film coating and the transmission of the tinted substrate:

(4) assuming that the thin-film coating is applied only to the front surface of the substrate and assuming that an anti-reflection coating (with T~l) is applied to the back surface of the substrate.

For light entering the back surface of the substrate, it first passes through the tint, is reflected from the thin-film filter on the front surface of the substrate, then passes through the tint a second time before striking the user's eyes. For this situation, the reflected light may be written

) = Timt (A)[l - Tmm (X)]Ttmt (X) = Rfi,,,, (£)T (X) « rlmt (λ)[ΤύΜ (X) - τ(λ)] (5)

At any particular wavelength, the fraction of light transmitted and reflected may be set by the transmission of the thin film coating and tint. For example, if about 20% transmission is desired at a desired wavelength (in this example about 480nm), then only certain combinations of thin film and tint transmissions may be used. Furthermore, if about 10% reflection is desired, then only a single combination of thin film and tint transmissions is allowed. These relationships may be described as follows:

(6)

Figure imgf000025_0001

The dose D experienced by melanopsin cells due to back reflected light into the user's eyes can be written similarly to the dose experienced by melanopsin cells due to transmitted light shown in Equation (1)

DR.mdan = J L(A)R(X)M(X)cU (8) where L is the light spectrum (in terms of intensity, power, photons/sec, etc), R is the spectral back reflection, and M is the normalized action potential response spectrum of melanopsin, as currently estimated from FIG. 1 as a Gaussian function centered at 480nm with a full-width at half-maximum of 52nm. For generality, it is assumed that L=l so as not to limit discussion to any specific light source, however analyses may be performed for any light source of known spectrum.

The normalized dose by back reflected light experienced by melanopsin cells may be calculated by

D Rn melon

R "--mmeelloann

-melon (9)

A similar dose and normalized dose can be calculated in association with the visual response spectrum

DR ^ = \ L(X)R(X)V(X)dA (10)

N 'R - vis

R - vis

DR-m{T = l (1 1) where V represents the normalized visual response spectrum. Ideally, backreflection would be reduced so that these dose values are close to zero.

The dose of back reflected light with respect to the action potential spectrum of the melanopsin pathway may be determined using Equation (8). The dose of back reflected light with respect to the visual spectrum may be determined using Equation (9). The doses of back reflected light may be used to design and manufacture an optical filter. For example, an appropriate level of tinting may be selected based on the maximum desired dose of back reflected light, whether across the action potential spectrum of the melanopsin pathway, across the visual spectrum, or both. Reduction of the dose and normalized dose of back reflected light experienced by melanopsin cells may reduce the symptoms experienced by a photophobic user.

The following tables illustrate additional embodiments of filter designs with some possible combinations of notch and tint transmissions that result in specific transmissions and backside reflections at, for example, about 480nm. Note that, due to the notch response, the transmission of light outside the notch will be greater than the transmission of light within the notch, so that the amount of back reflected light will be less than occurs at the notch center. Although these examples are specific to a notch centered near 480nm, other wavelengths may be selected as described herein.

Table 1 provides examples that maintain a fixed 10% backside reflection at a specific wavelength (around 480nm, for example) or range of wavelengths, with different transmissions through the frontside. This value of backside reflection might be desirable for therapeutic lenses that may be used in "open" style spectacle frames, for example, where light is allowed to strike the lenses from the top, bottom, and/or sides, thereby entering the backside of the lens and reflecting into the eyes of the user from the front-side thin-film coating. Other amounts of backside reflection may be desirable for other style spectacle frames (such as sport glasses, wraparound sunglasses, or other styles of frames).

Table 1 : transmission T back refl R Ttint Tfilm

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 further embodiments, but with greater backside reflection allowed. These designs may be more appropriate for "wrap" style spectacle or sport frames, which prevent light from entering the eyes except for that light which passes through the front-side of the lenses. Table 2:

Figure imgf000028_0001

Other embodiments of a filter may include fixing the notch transmission and adjusting the tint transmission to provide a given backside reflection value. Examples of these embodiments are shown in Table 3 below.

Table 3:

transmission Tf,|m back refl R Ttint 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 values described herein may be used to determine the maximum amount of back reflected light. For example, an R value of about 0.10 could be used as a desired amount of back reflected light weighted across the action potential spectrum of the melanopsin pathway, the visual spectrum, or both. As the R values are based on a desired wavelength to attenuate, other wavelengths of light may be attenuated based on a filter designed to achieve an R value equal to or less than values according to the tables above. For example, for a wavelength of about 480nm with an R value of about 0.10, the R value for a wavelength of about 470nm or 490nm may be less than 0.10, such as about 0.09. R values will generally decrease at wavelengths away from the desired notch center wavelength. For clarity, though the tables herein list the R value as a decimal value, these values may also be expressed as percentages.

These examples are not intended to limit the combinations appropriate for the present disclosure and are provided only to demonstrate some of the possible combinations that may be appropriate for therapeutic effects. Any number of other combinations are envisioned and may be appropriate for different levels of user light sensitivity, for different diseases, for different applications, and for different types of tints (e.g. gray, FL-41 , etc.), and different frame styles.

Manufacturing considerations may also be taken into account when performing filter design. For example, material deposition is typically accomplished using sputtering, evaporation, or chemical vapor deposition techniques. Deposition conditions may be optimized to minimize stress of the thin film materials. Oftentimes high temperature thermal annealing may be performed post-deposition to relax stress in the deposited materials, but annealing often cannot be applied to plastic lenses. Spectacle lenses represent curved substrates, so that achieving constant film thickness during deposition may be a challenge. To produce constant film thicknesses, modification of the target-source geometry in the deposition system may be used. For plastic lenses, low temperature deposition may be used, but may be optimized to produce low stress films. The following working examples describe tested optical filter designs and their results. Test notch coatings were produced on polycarbonate piano lenses with scratch resistant coatings. A thin layer of Cr was deposited on to the substrate to act as an adhesion layer for the thin film stack. The transmission spectrum through an example coated lens is shown in FIG. 18. The center of the notch is at about 482.9nm with width of about 55.5nm, with minimum transmittancc of about 24.5%. This embodiment of a filter blocks about 58% of the melanopsin action potential spectrum and blocks about 23% across the visible spectrum, with an FOM value of about 2.6.

In a preliminary clinical trial, migraine sufferers were recruited to wear spectacles with the therapeutic notch coating of FIG. 18. Participants wore therapeutic lenses for 2 weeks. For inclusion in the trial, all participants reported chronic daily headache, defined as more than 15 days with headache per month. A validated questionnaire, HIT6, was used to assess the effects of headaches on the participants' daily lives, both before and after wearing the therapeutic lenses. A tabulation of the HIT6 scores is shown in the following table. An average of about 6.6% improvement was obtained, consistent with a significant improvement in quality of life for the participants.

Participant HIT6 before HIT6 after Improvement

#1 61 57 6.6%

#2 76 68 1 1%

#3 65 62 4.6%

#4 55 48 13%

#5 70 68 2.9%

#6 69 65 5.8%

#7 61 58 4.9%

#8 63 60 4.8%

#9 69 60 13%

#10 68 67 1.5% #11 68 65 4.4%

In another working example, thin film notch coatings have been applied to FL-41 tinted lenses. The transmission and backside reflection spectra are shown in FIGS. 19 and 20. Different levels of FL-41 tint were applied to tintable scratch resistant layers (also called hard coatings) on the polycarbonate lenses. The multilayer notch filter was then applied to the front side of each lens, with a conventional anti-reflection coating applied to the backside of each lens. As can be seen from FIGS. 19 and 20, the FL-41 tint dramatically decreased the backside reflection. However, in the transmission, the notch response is red-shifted due to the slope of the FL-41 tint near 480nm. This shift may be compensated for by starting with a slightly blue-shifted notch design.

The following table lists the blocking levels across the melanopsin and visual response spectrum and the FOM values for each tint level. Similar results can be expected by utilizing other tints, such as gray tints such as "sun gray" from BPI.

Figure imgf000031_0001

The coatings described here can also be integrated with other technologies. For example, filter coatings can be applied to tinted lenses, photochromic materials may be incorporated, techniques for polarization can be included, other technologies may be integrated, or combinations thereof. In addition, combinations of filter technologies may be used, such as applying a nanoparticle filter coating on top of a multi-layer thin-film coating. Active materials, such as electro-optic materials, including electro-optic polymers, liquid crystals, or other electro-optic materials, piezoelectric materials, including piezoceramics such as pzt, or other piezoelectric materials may be used. FIG. 21 illustrates an exemplary embodiment of a method 2100 of manufacturing an optical filter for reducing the frequency and/or severity of photophobic responses. The method 2100 may be used to design at least one embodiment of a filter described herein. The method 2100 may include determining the appropriate light spectrum, as illustrated by act 2102. Determining the appropriate light spectrum may include consideration of specific lighting conditions, such as taking spectrophotometric measurements, in conditions such as indoor fluorescent lighting and/or computer screens in an office, shopping, or home environment, or outdoor lighting such as sunlight experienced due to normal outdoor activities or sporting activities. The light dose to be experienced by melanopsin cells may be determined (using, for example, Equation 1), as illustrated by act 2104. The light dose to be experienced across the visual response spectrum may be determined (using, for example, Equation 2), as illustrated by act 2106. An optical filter may be designed and manufactured using the first light dose and the second light dose, as illustrated by act 2108. The first light dose and the second light dose may be used to determine a figure of merit (FOM) as described herein. In other embodiments, the dose across the visual response spectrum may be considered for a portion or portions of the visible spectrum. For example, more or less than the entire visual response spectrum may be used.

FIG. 22 illustrates an exemplary embodiment of a method 2200 for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles. The method 2200 may be used in conjunction with at least one embodiment of a filter described herein. The method 2200 may include receiving an amount of light, as illustrated by act 2202. The light received may include direct or indirect light from one or more light sources. Less than a first amount of light weighted across the action potential spectrum of the melanopsin cells may be transmitted, as illustrated by act 2204. A second amount of light weighted across the visual light spectrum may be transmitted, as illustrated by act 2206. An optical filter may be manufactured using the first light dose and the second light dose, as illustrated by act 2208. The first light dose and the second light dose may be used to determine a figure of merit (FOM) as described herein. In other embodiments, the dose across the visual response spectrum may be reduced or separated. For example, more or less than the entire visual response spectrum may be used. It should be noted that, while the invention has been described in connection with the above described embodiments, these descriptions arc not intended to limit the scope of the invention to the particular forms set forth, but on the contrary, these descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the scope of the invention. Accordingly, the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and the scope of the present invention is limited only by the appended claims.

Claims

" CLAIMS What is claimed is:
1. An apparatus for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles by controlling light exposure to melanopsin ganglion cells in a retina over the action potential spectrum of the melanopsin ganglion cells of the human eye and a visual spectral response of the human eye, the apparatus comprising:
an optical filter configured to transmit less than a first amount of light weighted across the action potential spectrum of the melanopsin ganglion cells and to transmit more than a second amount of light weighted across the visual spectral response.
2. The apparatus of claim 1, wherein said first amount of light is about 50% of the light weighted across the action potential spectrum of the melanopsin ganglion cells and said second amount of light is about 75% or greater of the light weighted across the visual spectral response.
3. The apparatus of claim 1 , wherein said first amount of light is about 25% of the light weighted across the action potential spectrum of the melanopsin ganglion cells and said second amount of light is about 60% or greater of the light weighted across the visual spectral response.
4. The apparatus of claim 1 , wherein said first amount of light is approximately all of the light weighted across the action potential spectrum of the melanopsin ganglion cells.
5. The apparatus of claim 4, wherein said second amount of light is approximately all of the light outside of the action potential spectrum of the melanopsin ganglion cells, weighted across the visual response spectrum.
6. The apparatus of claim 1 , wherein a ratio of the attenuation of said first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells and the attenuation of said second amount of the light weighted across the visual spectral response is more than one.
7. The apparatus of claim 1 , wherein said first amount of light is substantially all light below a long pass filter wavelength within the action potential spectrum of the melanopsin ganglion cells and said second amount of light is all light across the visual spectral response with a wavelength above said long pass filter wavelength.
8. The apparatus of claim 7, wherein said long pass filter wavelength is 500nm.
9. The apparatus of claim 1, wherein the action potential spectrum of the melanopsin ganglion cells is between about 454nm and about 506nm.
10. The apparatus of claim 1, wherein said second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells.
1 1. The apparatus of claim 1 , wherein said second amount of light includes a third amount of light having a wavelength that is greater than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells.
12. The apparatus of claim 1, wherein said second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and a fourth amount of light that is greater than the maximum relative response of the action potential spectrum of melanopsin.
13. The apparatus of claim 1, wherein said second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is lower than a relative response at a standard deviation of the action potential spectrum of melanopsin.
14. The apparatus of claim 1 , wherein said second amount of light includes a third amount of light having a wavelength that is greater than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is greater than a relative response at a standard deviation of the action potential spectrum of melanopsin.
15. The apparatus of claim 1 , wherein said second amount of light includes a third amount of light having a wavelength that is lower than a maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is lower than a relative response at a standard deviation of the action potential spectrum of melanopsin and a fourth amount of light having a wavelength that is greater than the maximum relative response of the action potential spectrum of the melanopsin ganglion cells and is greater than the relative response at the standard deviation of the action potential spectrum of the melanopsin ganglion cells.
16. The apparatus of claim 1 , wherein said second amount of light includes at least one wavelength that is less than about 480nm.
17. The apparatus of claim 1, wherein said second amount of light includes at least one wavelength that is more than about 480nm.
18. The apparatus of claim 1 , wherein said second amount of light includes at least one wavelength that is less than about 480nm and at least one wavelength that is more than about 480nm.
19. The apparatus of claim 1 , wherein said first amount of light is a dose of light experienced by the melanopsin ganglion cells of a subject (Dmeian) and said second amount of light is a dose of light experienced over the visual response spectrum (Dvis), and wherein a ratio including said first amount of light and said second amount of light is defined as a figure of merit (FOM), the figure of merit being determined by:
Figure imgf000036_0001
where
Figure imgf000036_0002
is said first amount of light in the absence of an optical filter, and DVis(T: T) is said second amount of light in the absence of an optical filter.
20. The apparatus of claim 19, wherein the figure of merit of said optical filter is about one.
21. The apparatus of claim 19, wherein the figure of merit of said optical filter is greater than about one.
22. The apparatus of claim 19, wherein the figure of merit of said optical filter is greater than about 1.3.
23. The apparatus of claim 19, wherein the figure of merit of said optical filter is greater than about 1 ,5.
24. The apparatus of claim 19, wherein the figure of merit of said optical filter is greater than about 1.8.
25. The apparatus of claim 24, wherein the figure of merit of said optical filter is greater than about 2.75.
26. The apparatus of claim 25, wherein the figure of merit of said optical filter is greater than about 3.
27. The apparatus of claim 26, wherein the figure of merit of said optical filter is greater than about 3.3.
28. The apparatus of claim 1, wherein said first amount of light defines a spectral width that has a median at a median of the action potential spectrum of the melanopsin ganglion cells.
29. The apparatus of claim 1, wherein said first amount of light and said second amount of light are determined based on the characteristics of ambient light.
30. The apparatus of claim 1, wherein said first amount of light and said second amount of light are selectively adjustable by way of a transition type coating.
31. The apparatus of claim 1 , wherein said optical filter includes at least one layer configured to minimize or reduce the effect of an angle of incidence of the received light.
32. The apparatus of claim 1, wherein said optical filter further comprises a substrate that includes a tint by impregnation or by coating.
33. The apparatus of claim 1, wherein the optical filter is further configured to attenuate a third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells.
34. The apparatus of claim 33, wherein the third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells is less than about 50%.
35. The apparatus of claim 33, wherein the third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells is less than about 25%.
36. The apparatus of claim 33, wherein the third amount of back reflected light weighted across the action potential spectrum of the melanopsin ganglion cells is less than about 10%.
37. The apparatus of claim 1 , wherein the optical filter is further configured to attenuate more than a fourth amount of back reflected light weighted across the visual spectral response.
38. The apparatus of claim 37, wherein the fourth amount of back reflected light weighted across the visual spectral response is less than about 50%.
39. The apparatus of claim 37, wherein the fourth amount of back reflected light weighted across the visual spectral response is less than about 25%.
40. The apparatus of claim 37, wherein the fourth amount of back reflected light weighted across the visual spectral response is less than about 10%.
41. A system for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles by controlling light exposure to melanopsin ganglion cells in a retina over the action potential spectrum of the melanopsin ganglion cells of the human eye and a visual spectral response of the human eye, the system comprising:
a substrate;
a first layer disposed on the substrate, the first layer comprising a high index material; and
a second layer disposed adjacent the first layer, the second layer comprising a low index material.
42. The system of claim 41, wherein the substrate has a front surface and a back surface, wherein the first layer and the second layer are disposed on the front surface
43. The system of claim 41, wherein the substrate is tinted.
44. The system of claim 41 , wherein the high index material comprises Ti02.
45. The system of claim 41 , wherein a thickness of the first layer is 165nm.
46. The system of claim 41, wherein the low index material comprises Si02.
47. The system of claim 41, wherein the low index material comprises MgF2.
48. The system of claim 41 , wherein a thickness of the first layer is 40nm.
49. The system of claim 41, wherein high index material of the first layer is Ti02 and the low index material of the second layer is Si02 and further comprising one or more additional alternating adjacent layers of Ti02 and Si02, wherein the first additional layer is adjacent the second layer and wherein the last additional layer may be MgF2; Si02 or Ti02 and is adjacent the outer layer.
50. The system of claim 41, further comprising additional layers and/or types of material, wherein the materials cooperate to transmit less than a first amount of light weighted across the action potential spectrum of the melanopsin ganglion cells and to transmit more than a second amount of light weighted across the visual spectral response.
51. The system of claim 41 , wherein increasing the number of layers in the optical filter increases transmission of light outside the action potential spectrum.
52. The system of claim 41, wherein the optical filter is a notch filter that comprises 10 dielectric layers, the notch filter being configured to block about 61% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 21% attenuation weighted across the visual spectral response.
53. The system of claim 41, wherein the notch filter comprises 15 dielectric layers, the notch filter being configured to block about 70% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 25% attenuation weighted across the visual spectral response.
54. The system of claim 41, wherein the notch filter comprises 19 dielectric layers, the notch filter being configured to block about 89% light weighted across the action potential spectrum of the melanopsin ganglion cells, while causing about 29% attenuation weighted across the visual spectral response.
55. The system of claim 41, wherein the substrate further comprises a first side, and wherein the first layer is applied to the first side, and wherein an anti-reflection coating is applied to a side of the substrate opposite the first side.
56. A method of manufacturing an optical filter for reducing the frequency and/or severity of photophobic responses by controlling light exposure to melanopsin ganglion cells over the action potential spectrum of the melanopsin ganglion cells of the human eye and a visual spectral response of the human eye, the method comprising:
determining an appropriate light spectrum;
determining a first light dose to be experienced by the melanopsin ganglion cells in the subject;
determining a second light dose associated with the visual response spectrum; and
manufacturing an optical filter using the first light dose and the second light dose.
57. The method of claim 56, further comprising determining an action potential spectrum of an individual's melanopsin ganglion cells.
58. The method of claim 56, wherein the optical filter is configured to attenuate the first amount of light based on the individual's melanopsin ganglion cells.
59. The method of claim 56, further comprising manufacturing the optical filter based on visual response spectrum characteristics.
60. The method of claim 56, wherein the optical filter is a notch filter.
61. The method of claim 60, wherein the notch filter is configured to block light that strikes at a non-normal incidence angle.
62. The method of claim 60, wherein the notch filter comprises a filter optimized for a plurality of tilted incidence angles.
63. The method of claim 60, wherein the notch filter is designed with a slight red shift.
64. The method of claim 60, wherein the notch filter includes a filter notch that attenuates light across a spectral width.
65. The method of claim 60, wherein manufacturing of the optical filter includes widening the filter notch to increase attenuation of the effective melanopsin action potential spectrum.
66. The method of claim 60, wherein manufacturing of the optical filter includes deepening the filter notch to increase attenuation of the effective melanopsin action potential spectrum.
67. The method of claim 60, wherein manufacturing of the optical filter includes widening the filter no tch and deepening the filter notch to increase attenuation of the effective melanopsin action potential spectrum.
68. The method of claim 56, wherein manufacturing of the optical filter includes material deposition that incorporates target-source geometry modification.
69. The method of claim 56, wherein manufacturing of the optical filter includes using dielectric multi-layers, embedded nanoparticle coatings, a color filter, tint, resonant guided-mode filter, a rugate filter, and any combination thereof.
70. The method of claim 69, wherein the embedded nanoparticle coatings include at least one of metallic nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in a core and a shell material serving as a shell.
71. The method of claim 70, wherein the at least metallic nanoparticles include at least one of Al, Ag, Au, CU, Ni, Pt, or other metallic nanoparticles, wherein the dielectric nanoparticles include at least one of Ti02, Ta205, or other dielectric nanoparticles.
72. The method of claim 70, wherein the semiconductor nanoparticles or quantum dots include at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles.
73. The method of claim 70, wherein a shape of the embedded nanoparticles in the embedded nanoparticle coatings is spherical, elliptical, or otherwise shaped.
74. The method of claim 70, further comprising determining an extinction spectrum of the embedded nanoparticles using Mie scattering theory.
75. The method of claim 56, further comprising determining a third light dose of back reflected light to be experienced by the melanopsin ganglion cells in the subject.
76. The method of claim 75, further comprising determining a fourth light dose of back reflected light associated with the visual response spectrum.
77. The method of claim 76, wherein manufacturing an optical filter further comprises using the third light dose and the fourth light dose.
78. A method for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles using the action potential spectrum of the melanopsin cells of the human eye and the visual spectral response of the human eye, the method comprising:
receiving an amount of light;
with the apparatus of claim 1, transmitting less than a first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells; and
with the apparatus of claim 1 , transmitting a second amount of the light weighted across the visual spectral response.
79. A system for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles using the action potential spectrum of the melanopsin ganglion cells of the human eye and the visual spectral response of the human eye, the system comprising:
a light source; and
the apparatus of claim 1.
80. A method for reducing the frequency and/or severity of photophobic responses or for modulating circadian cycles using the action potential spectrum of the melanopsin cells of the human eye and the visual spectral response of the human eye, the method comprising:
receiving an amount of light from the light source of claim 79;
with the system of claim 79, transmitting less than a first amount of the light weighted across the action potential spectrum of the melanopsin ganglion cells; and with the system of claim 79, transmitting a second amount of the light weighted across the visual spectral response.
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