Note: Descriptions are shown in the official language in which they were submitted.
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METHODS, SYSTEMS, AND APPARATUS FOR REDUCING THE
FREQUENCY AND/OR SEVERITY OF PHOTOPHOBIC RESPONSES OR
FOR MODULATING CIRCADIAN CYCLES
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Patent Application Ser.
No.
15/673,264, filed August 9, 2017, entitled "METHODS, SYSTEMS, AND
APPARATUS FOR REDUCING THE FREQUENCY AND/OR SEVERITY OF
PHOTOPHOBIC RESPONSES OR FOR MODULATING CIRCADIAN CYCLES,"
to the disclosure of which is incorporated herein by reference in its
entirety.
BACKGROUND OF THE DISCLOSURE
1. The Field of the Invention
[0002]
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
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
[0003] The
retina of the eye contains various photoreceptor cells. These
photoreceptor cells include rods (which are involved in black-and-white and
low light
vision), cones (which are involved in daytime vision and color perception),
and
melanopsin ganglion cells.
[0004] 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
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 Good
et al. The Use of Tinted Glasses in Childhood Migraine Headache. 1991 Sep;
31(8):533-6 PMID 1960058 and Blackburn et al. FL-41 Tint Improves Blink
Frequency
Light Sensitivity and Functional Limitations in Patients with Benign Essential
Blepharospasm Ophthalmology. 2009 May;116(5):997-1001 PMID 19410958, which
are both hereby incorporated by reference in their entirety In addition to
pain pathways,
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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.
[0005] 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 KP Jr. Entrainment of the
human circadian system by light. J Biol Rhythms. 2005 Aug;20(4):326-38.
Review.
PubMed PMID: 16077152, both of which are hereby incorporated by reference in
their
entireties.
[0006]
Rhodopsin is the photosensitive molecule in the rods and cones of the eye.
Rhodopsin has two metastable isomers including an active and an inactive
state. When
exposed to light, the rhodopsin isomerizes to an inactive isoform. The
inactive isoform
of rhodopsin can be recycled in the retinoid cycle. During the retinoid cycle,
the
rhodopsin leaves the photoreceptor and enters the retinal pigment epithelium.
After
being recycled to an active isoform, the rhodopsin returns to the
photoreceptor. The
melanopsin of the melanopsin ganglion cells is believed to undergo a similar
process
as described in Mure LS, Cornut PL, Rieux C, Drouyer E, Denis P, Gronfier C,
Cooper
HM. Melanopsin bistability: a fly's eye technology in the human retina. PLoS
One.
2009 Jun 24;4(6):e5991. PubMed PMID: 19551136, which is incorporated hereby by
reference in its entirety.
[0007]
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
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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
[0008] As the
melanopsin ganglion cells are sensitive to light wavelengths near
480nm and are associated with 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 may affect the frequency and/or severity of
photophobic
responses, so it may be beneficial in some circumstances to reduce the direct
light
stimulation of these cells, or in other circumstances to reduce the amount of
exposure
to light not directly associated with the stimulation of these cells. These
photophobic
responses include migraine headache, light sensitivity associated with a
concussion or
traumatic brain injury, light sensitive epilepsy, and light sensitivity
associated with
benign essential blepharospasm. 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 or other
portions of
the eye are provided.
[0009] 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 absorption spectrum of the bistable isoforms of
melanopsin,
and to transmit more than a second amount of light weighted across the visual
spectral
response. As examples, the light spectrum associated with the absorption
spectrum of
the active isoform of melanopsin is near 480nm wavelength, and a light
spectrum
associated with the absorption spectrum of the inactive isoform of melanopsin
is near
590nm wavelength.
[0010] In some
embodiments, the first amount of light is about 50% of the light
weighted across the absorption spectrum of one or both of the bistable
isoforms of
melanopsin and the second amount of light is about 75% or 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 absorption spectrum of one or both
of the
bistable isoforms of melanopsin 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
absorption
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spectrum of one or both of the bistable isoforms of melanopsin. The second
amount of
light, in still further embodiments, is approximately all of the light outside
of the
absorption spectrum of one or both of the bistable isoforms of melanopsin
and/or
weighted across a spectrum that lies outside the absorption spectrum of one or
both of
the bistable isoforms of melanopsin, 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 absorption spectrum of one or both of the bistable
isoforms of
melanopsin to the attenuation of the second amount of the light weighted
across the
visual spectral response is more than one.
[0011] 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 first amount of light is substantially all light above a
short pass filter
wavelength near 590nm and the second amount of light may be substantially all
light
across the visual spectral response with a wavelength below the short pass
filter
wavelength.
[0012] In some
embodiments, the second amount of light includes a third amount
of light having a wavelength that is less than a maximum relative response of
the action
potential spectrum of the melanopsin ganglion cells and/or greater than about
590nm.
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
absorption
spectrum of one or both of the bistable isoforms of melanopsin. 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 absorption
spectrum
of one or both of the bistable isoforms of melanopsin and a fourth amount of
light that
is greater than the maximum relative response of the absorption spectrum of
one or both
of the bistable isoforms of melanopsin.
[0013] In some
embodiments, the first amount of light is a dose of light (i.e. across
the absorption spectrum of one or both of the bistable isoforms of melanopsin)
experienced by a cell in the eye ¨ retinal ganglion cells or other cells of a
subject (Drec)
- and the second amount of light is a dose of light experienced over the
visual response
spectrum (Dvis), and wherein a ratio including the first amount of light and
the second
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amount of light is defined as a figure of merit (FOM), the figure of merit
being
determined by:
rPC
1
FOM = Drõ (T =1)
Dvis
1
Dv,s(T =1)
[0014] where
Drec(T=1) is the first amount of light in the absence of an optical filter,
and Dvis(T=1) is the 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.
(c) [0015] In
some embodiments, the first amount of light defines a spectral width that
has a median at a median of the absorption spectrum of one or both of the
bistable
isoforms of melanopsin. 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, -photochromic, or
electrochromic type
dye, pigment or coating.
[0016] 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.
[0017] 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.
[0018] 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.
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[0019] 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 one or both of the bistable isoforms of melanopsin 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.
[0020] 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
to ganglion
cells. In still further embodiments, the optical filter is manufactured based
on
visual response spectrum characteristics.
[0021] 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.
[0022] 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
TiO2, 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.
[0023] An
embodiment of a method for reducing the frequency and/or severity of
photophobic responses or for modulating circadian cycles is described. The
method
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includes receiving an amount of light. Less than a first amount of the light
weighted
across the absorption spectrum of one or both of the bistable isoforms of
melanopsin is
transmitted. More than a second amount of the light weighted across the visual
spectral
response is transmitted. The attenuation of light weighted across the
absorption
spectrum of one or both of the bistable isoforms of melanopsin disrupts the
isomerization of one or both of the bistable isoforms of melanopsin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] 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.
[0025] 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.
[0026] FIG. 2 illustrates the measured transmission spectrum of an
exemplary "FL-
41 35" filter across the "effective action potential spectrum" of melanopsin.
[0027] FIG. 3
illustrates the measured transmission spectrum of an exemplary "FL-
41 35" filter across the visible light spectrum.
[0028] FIG. 4
illustrates the measured transmission spectrum of an exemplary "FL-
.. 41 55" filter across the "effective action potential spectrum" of
melanopsin.
[0029] FIG. 5
illustrates the measured transmission spectrum of an exemplary "FL-
41 55" filter across the visible light spectrum.
[0030] FIG. 6
is an example of a filter using multi-layer dielectric thin films of
distinct refractive indices.
[0031] 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.
[0032] FIG. 8
illustrates an exemplary method for designing an optical filter to
block light absorption by melanopsin cells
[0033] FIG. 9
illustrates the measured transmission spectrum of one embodiment
of a filter across the "effective action potential spectrum" of melanopsin.
[0034] FIG. 10
illustrates the measured transmission spectrum of the embodiment
of a filter in FIG. 9 across the visible light spectrum.
[0035] FIG. 11
illustrates the measured transmission spectrum of another
embodiment of a filter across the "effective action potential spectrum" of
melanopsin.
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[0036] FIG. 12
illustrates the measured transmission spectrum of a further
embodiment of a filter across the "effective action potential spectrum" of
melanopsin.
[0037] FIG. 13
illustrates the measured transmission spectrum of a still further
embodiment of a filter across the "effective action potential spectrum" of
melanopsin.
[0038] FIG. 14
illustrates the measured transmission spectrum of the embodiment
of a filter in FIG. 13 across the visible light spectrum.
[0039] 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.
[0040] 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.
[0041] 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.
[0042] FIG. 18A
and B illustrate the measured transmission spectrum of an
embodiment of a filter centered at about 480nm and an embodiment of a filter
centered
at about 620nm.
[0043] FIG. 19
illustrates the measured transmission spectrum of multiple
embodiments of filters centered at about 480nm with varying degrees of tint.
[0044] FIG. 20
illustrates the backside reflection spectra of the embodiments of
filters in FIG. 19.
[0045] FIG. 21
illustrates an exemplary embodiment of a method of manufacturing
an optical filter.
[0046] FIG. 22 illustrates an exemplary embodiment of a method for reducing
the
frequency and/or severity of photophobic responses or for modulating circadian
cycles.
[0047] FIG. 23
illustrates an embodiment of a composite filter configured to
preferentially attenuate two ranges of wavelengths.
[0048] FIG. 24
illustrates an embodiment of a method of manufacturing a
composite optical filter.
[0049] FIG. 25
illustrates an embodiment of a method using a composite filter for
reducing the frequency and/or severity of photophobic responses or for
modulating
circadian cycles.
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[0050] FIG. 26A
and B illustrate the transmission spectra of gray tinted lenses
coatings centered at 480nm and 620nm, respectively.
[0051] FIG. 27
schematically illustrates the cyclic isomerization of a bistable
pigment.
[0052] FIG. 28
illustrates the reactive spectra of active and inactive melanopsin in
the eye.
[0053] FIG. 29
illustrates an embodiment of a method of disrupting the
isomerization of one or both of the bistable isoforms of melanopsin.
[0054] FIG. 30
illustrates the relative response versus the wavelength of light
according to sample color-matching functions.
[0055] FIG. 31
illustrates the relative response versus the wavelength of light
according to sample color-matching functions when a 480 nm filter is used.
[0056] FIG. 32
illustrates the relative response versus the wavelength of light
according to sample color-matching functions when both a 480 nm filter and a
590 nm
filter are used.
DETAILED DESCRIPTION
[0057] 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.
[0058] 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.
[0059]
Different individuals experience photophobic responses in different ways.
The wavelengths and, therefore, pathways that trigger adverse reactions to
light can
vary depending on the patient. However, there are some common wavelengths that
are
more commonly associated with photophobic responses than others. For example,
the
melanopsin ganglion cells in the eye are sensitive to light at a wavelength of
about
480nm. In some individuals, this may be linked to those individual's light-
sensitive
neurological conditions. Controlling exposure to light near the 480nm
wavelength may
yield benefits to those individuals and reduce or prevent their light-
sensitive
neurological conditions. Alternatively or in addition, regulating exposure to
that same
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light may also assist in controlling an individual's circadian rhythms. In the
same or
other individuals, regulating the exposure of the eye to light near a 620nm
wavelength
or other wavelengths may also yield benefits in reducing or preventing light-
sensitive
neurological conditions or managing an individual's circadian rhythms. While
the
following example refers to the attenuation of light having wavelengths near
480nm
and the exposure of melanopsin ganglion cells to the same light near 480nm, it
may be
understood that a similar filter and methods may be used to attenuate light at
other
wavelengths and received by other cells in the eye. For example, a similar
filter and
method may be used to attenuate light at or about 620nm. In another example, a
similar
to filter and method may be used to attenuate light at or about 590nm.
[0060] 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.
[0061] 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.
[0062] 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,
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gas vapor, etc.), or any other optical element. These optical filters may be
applied to
crown glasses (including BK7), flint glasses (including BaF8), SiO2, plastics
(such as
polycarbonate, CR-39, and trivex), other substrates, and combinations thereof
[0063] 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
ml 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.
[0064]
Furthermore, it has also been recently clinically demonstrated that
wavelengths near 620nm also contribute to photophobic effects in certain
individuals.
While the precise pathways for the neurological effects are not currently
fully
understood, benefits may be achieved by preferentially attenuating light with
wavelengths near 620nm, as well.
[0065]
Melanopsin has bistable isoforms that each exhibit unique absorption
spectra. The isoforms may be an active isoform and an inactive isoform. The
active
isoform may be physiologically active. The inactive isoform may be
physiologically
inactive. Absorption of light in accordance with each isoform's absorption
spectrum
may lead to the isomerization of the melanopsin. Benefits may be achieved by
disrupting, limiting, or preventing the isomerization of melanopsin by
attenuating light
at or about 590nm.
[0066] 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
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increases in intensity, by for example moving to an outdoor environment, the
"FL-41
35" may not be as effective.
[0067] 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.
[0068] 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.
[0069] 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.
[0070] One
example of a more desirable optical filter for the treatment of light
sensitive conditions may include a long-pass filter. To regulate exposure of
the
melanopsin ganglion cells to wavelengths of about 480nm, a long pass filter
may highly
transmit wavelengths longer than about 500nm or 520nm, while attenuating light
at
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wavelengths shorter than about 500nm or 520nm. Similarly, to regulate exposure
of
cells in the human eye to wavelengths of about 620nm, a short pass filter may
highly
transmit wavelengths shorter than 600nm or about 580nm, while attenuating
light at
wavelengths longer than about 600nm or about 580nm.
[0071] Other examples of
more desirable optical filters may include filters that only
block the spectrum of light absorbed by melanopsin or other specific
wavelengths,
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. In the case of melanopsin 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.
[0072] 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. TiO2, 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
[0073] 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
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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.
[0074] 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.
[0075] 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.
[0076] 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,
when attenuating light near 480nm approaching melanopsin ganglion cells, 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. Depending
on the wavelength attenuated, the degree of red-shift or blue-shift may vary.
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
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consideration. One or more of these considerations may be addressed by
combining
the filter with some form of tinting.
[0077] 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
Dmerõ LoTomodii (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=1 so as not to limit
discussion
to any specific light source, however analyses may be performed for any light
source
of known spectrum.
[0078] A similar dose can be calculated in association with the visual
response
spectrum
Dv1s. =j LWT(i)v(i)thi
(2)
where V represents the normalized visual response spectrum.
[0079] 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
melan
Nmelan = D
D melan(T ¨ 0
[0080] The "attenuation" of the dose may be written as, for example,
A melan = 1 ¨ Nmelan =1 Delan
m
Dmelan ¨ 1)
[0081] 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
D
1 melan
FOM
D1 (T 0
=
vis
1
Dv(T = I) (3)
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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 FOM>1
may be
desirable. For the FL-41 tint, FOM is about 1.
[0082] 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.
[0083] 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.
[0084] 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
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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.
[0085] 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
[0086] 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.
[0087] 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 SiO2. MgF2 is commonly used in single
and
multi-layer anti-reflection coatings. Example high index materials include
metal oxides
such as TiO2, Ti305, ZrO2, and Ta205, and Si3N4. Numerous other suitable
materials
can be used, including polymer layers.
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[0088] Optical
filters for attenuating light near various wavelengths, such as
480nm, 620nm, or other specific wavelengths, may follow similar designs. 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 5i02 and the high
index
material TiO2, 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 (TiO2 with 165nm thickness) adjacent to the
substrate.
This filter has FOMa
Material Thickness (nm)
MgF2 126
Si02 212
TiO2 125
Si02 134
TiO2 129
Si02 62
TiO2 12
Si02 51
TiO2 26
Si02 40
TiO2 165
[0089] 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, such as to 620nm. In another example, the spectral
position
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may be otherwise positioned to achieve specific results, such as to attenuate
wavelengths other than those of the action potential spectrum of the
melanopsin
pathway.
[0090] 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.
[0091] 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.
[0092]
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 (TiO2 with 160.3nm thickness) adjacent to the substrate.
Material Thickness (nm)
MgF2 179.9
Si02 152.3
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TiO2 75.8
SiO2 16.9
TiO2 80.5
SiO2 35.1
TiO2 38.0
SiO2 128.6
TiO2 66.5
SiO2 17.7
TiO2 55.5
SiO2 67.5
TiO2 88.3
SiO2 22.0
TiO2 63.1
SiO2 30.7
TiO2 84.2
SiO2 34.8
TiO2 160.3
[0093] 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.
[0094] 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.
[0095] 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.
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[0096] This
embodiment of a filter has the following layer properties listed in the
table below from the outermost layer (MgF2) to the innermost layer (TiO2 with
127nm
thickness).
Material Thickness (nm)
MgF2 117
TiO2 88
SiO2 190
TiO2 78
SiO2 192
TiO2 90
SiO2 37
TiO2 140
SiO2 134
TiO2 127
[0097] 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.
Material Thickness (nm)
Si02 58.6
TiO2 117.0
Si02 138.0
TiO2 57.4
Si02 18.8
TiO2 41.9
Si02 128.5
TiO2 149.9
Si02 52.1
TiO2 161.1
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Si02 187.7
TiO2 5.4
SiO2 45.9
TiO2 264.9
SiO2 33.1
TiO2 9.9
SiO2 208.5
[0098] 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:
= Tfilm ()AIM (A) (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 Tz1) is applied to the back
surface
of the substrate.
[0099] 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
R(A) = T tint (A)F Tfilm WiTimt (A) = Rfilm WTti2M (A) = T t int (4T tim (A) ¨
OA (5)
[00100] 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:
Tti2nt (1) TOTtint (1) R(A) = (6)
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Tot)Tfilm (A) = T(2) (7)
[00101] 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-melan = LoRomoco-, (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=1 so as not to limit discussion to any specific light source, however
analyses may be
performed for any light source of known spectrum.
[00102] The normalized dose by back reflected light experienced by melanopsin
cells may be calculated by
DR¨melan
NR ¨ rne Ian n
1-"melanki 1) (9)
[00103] A similar dose and normalized dose can be calculated in association
with
the visual response spectrum
DR,s = j LoRovoco, (10)
vi
S
R¨ s
D v,s(T =1) (11)
where V represents the normalized visual response spectrum. Ideally,
backreflection
would be reduced so that these dose values are close to zero.
[00104] 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.
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[00105] 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.
[00106] Table 1 provides examples that maintain a fixed 10% backside
reflection at
a specific wavelength (around 480nm, for example) or range of wavelengths,
with
to 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 Tfiim
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
[00107] 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:
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transmission T back refl R Twit Tfiim
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
[00108] 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 Tfilm back refl R Tfim 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
[00109] 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,
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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.
[00110] 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.
[00111] 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.
[00112] The following working examples describe tested optical filter designs
and
their results. Test notch coatings were produced on polycarbonate or CR-39
plano
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. 18A. The center of the notch
is at
about 482.9nm with width of about 55.5nm, with minimum transmittance 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 contrast, FIG. 18B depicts a transmission spectrum of a
coated
lens with a 620nm notch filter.
[00113] In a preliminary clinical trial, migraine sufferers were recruited to
wear
spectacles with the therapeutic notch coating of FIG. 18A. 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
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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 11%
#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%
[00114] 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
IA) layers (also called hard coatings) on the polycarbonate or CR-39
lenses. The multi-layer
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.
[00115] 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.
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FL-41 tint level Melanopsin Visual blocking FOM
blocking
0% 67.5% 28.8% 2.3
15% 71.3% 36.9% 1.9
35% 78.9% 53.7% 1.5
50% 88.0% 70.4% 1.3
[00116] 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.
to [00117] 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.
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[00118] 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
to 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.
[00119] In addition to regulating the exposure of melanopsin ganglion cells to
light
near 480nm, it has been demonstrated through clinical testing that attenuation
of light
at a wavelength of about 620nm may also yield improvements in alleviating
symptoms
associated with light sensitivity. Although light wavelengths at about 620nm
are not
believed to act on the melanopsin ganglion cells, attenuation of light at
about 620nm
has been demonstrated to reduce symptoms of light sensitivity in some people,
such as
pain or discomfort in response to light, and the frequency and/or severity of
migraine
and other headaches, and may also prove effective for some in the treatment of
blepharospasm, post-concussion/TBI syndrome, sleep disorders, epilepsy.
[00120] In one embodiment, improvements may be realized by attenuating light
between about 580nm and about 650nm. In another embodiment, improvements may
be realized by attenuating light between about 600nm and about 640nm. In yet
another
embodiment, improvements may be realized by attenuating light using a filter
substantially centered at a wavelength of 620nm with a full-width at half-
maximum of
about 55nm.
[00121] Additionally, a filter may attenuate light wavelengths in multiple
ranges.
For example, an embodiment of a filter may attenuate light at about 620nm in
addition
to attenuating light at about 480nm. In another embodiment, a filter may
preferentially
attenuate light wavelengths from about 450nm to about 510nm and from about
580nm
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to about 640nm. In yet another embodiment, a filter may attenuate light
between about
470 and about 490 and between about 610nm and about 630nm.
[00122] An optical filter may be made in accordance with the previously
described
processes and using the previously described materials. For example, a 620nm
optical
filter may comprise a high pass filter, a low pass filter, or an optical notch
filter. The
optical notch filter may comprise a plurality of layers of dielectric
materials,
nanoparticles distributed on or embedded in a host medium, or a combination
thereof
In addition, any of the aforementioned combinations may be used in conjunction
with
a dye incorporated in a substrate. By way of example, producing short pass or
notch
filters may include using alternating layers of high and low refractive index
materials.
Example low index dielectric materials include MgF2 and SiO2. Example high
index
materials include metal oxides such as TiO2, Ti305, ZrO2, and Ta205, and
Si3N4.
Numerous other suitable materials can be used, including polymer layers.
[00123] Similarly to the embodiments that are intended to attenuate
wavelengths
absorbed by the melanopsin ganglion cells and were described previously, an
optical
filter designed to attenuate wavelengths at about 620nm may be manufactured
according to a similar FOM. The light dose D received at about 620nm can be
written
Dõc,620 = LoToR620ociu(12)
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 R620 is
the idealized response spectrum at about 620nm, which may be estimated as a
Gaussian
function centered at 620nm with a full-width at half-maximum of 50, 55 or 60
nm,
although other values are anticipated and may prove therapeutic. For
generality, it is
assumed that L=1 so as not to limit discussion to any specific light source,
however
analyses may be performed for any light source of known spectrum.
[00124] A similar dose can be calculated in association with the visual
response
spectrum
Dws L(zi)T(zi)V0)dzi.
(13)
where V represents the normalized visual response spectrum.
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[00125] The
effect of an optical filter, such as a nanoparticle notch filter, is to reduce
the dose, as described by taking the ratio of dose calculated with the filter
to dose
without the filter, for example
Drec,620
N rec,620
Lirec,620 (1 1)
[00126] The "attenuation" of the dose may be written as, for example,
Drec 620_
Arec,620 1 Nrec,620 1 n
rec 620 (T
[00127] An FOM can also be defined which compares the blocking of the light at
about 620nm to the blocking of the visual response spectrum
1 Drec 620
FOM = Drec 620(1 1)
Dvis
1
Dv,s(T =1)
(14)
to which represents the ratio of the attenuation of light at about 620nm 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 620nm, the
comparison becomes more stringent as a smaller full width half maximum value
is used.
For example, when R(2), the Gaussian distribution used in the estimate, has a
full width
half maximum of 50nm describes a more specific optical filter than that when
the
estimate includes an R(2) having a 60nm full width half maximum.
[00128] The optical filter may comprise a multilayer dielectric film similar
to that
described for the attenuation of light to which melanopsin cells are
sensitive, or the
optical filter may comprise a nanoparticle-based optical filter, a color
filter, a tint, a
resonant guided-mode filter, a rugate filter, or any combination thereof A
nanoparticle-
based optical notch filter may comprise nanoparticles distributed on the
surface of or
embedded in a host medium. Such a filter may therefore be used in a
substantially
transparent host medium, such as the lens material of eyeglasses or simply
applied to a
surface thereof For example, the filter may be disposed on the surface of
eyeglass
lenses to attenuate light approaching a user's eyes. In another application,
the filter
may be disposed on the source of light directly, for example, over an
electronic display
such as computer screen or on a lighting source such as a light bulb or
anuation of light
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by nanoparticle-based notch filter may be adjusted via the shape of the
nanoparticles,
the amount or density of nanoparticles on or embedded in the host medium, the
composition of the nanoparticles, the size of the nanoparticles, and the index
of
refraction of the host medium. The attenuation spectrum of a nanoparticle-
based optical
notch filter may therefore be tuned to a particular curve by selecting
materials and
distributions that center the curve at a desired wavelength and a produce an
attenuation
curve with a maximum attenuation at a desired wavelength value and an
appropriate
shape and full width half maximum.
[00129] For example, increasing the index of refraction of the host medium of
the
nanoparticles may shift the attenuation spectrum toward longer wavelengths, as
may
utilizing larger particle sizes, including solid and core-shell particles,
and/or utilizing
other metals. The attenuation spectrum changes because the attenuation is due,
at least
in part, to localized surface plasmonic resonance (LSPR). The scattering due
to the
LSPR is proportional to the relative index of the refraction of the host
medium.
Therefore, when the index of refraction of the host medium increase, not only
does the
attenuation spectrum redshift, but the amount of scattering, and hence the
amount of
attenuation of light, increases as well.
[00130] The position and amount of scattering due to the LSPR is at least
partially
dependent on the relative index of refraction between the particles and the
host medium.
The relative index of refraction can also, therefore, be altered by changing
the
nanoparticle composition. The nanoparticles may be solid, consisting of a
single
material, or a core-shell composition having a core of a first material and a
shell of a
second material. In either case, the materials may be a single element, a
compound, or
an alloy. As described earlier, the nanoparticles may include metallic
nanoparticles
(e.g. Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (e.g. TiO2, 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 By
way of
example, increasing the proportion of Ag in an Ag/A1 alloy solid nanoparticle
may
redshift and increase the amplitude of the attenuation curve for that
nanoparticle.
[00131] In addition, the nanoparticles used may have cross-sections including
a
circle, an ellipse, a rectangle, a hexagon, an octagon, or other polygon.
Spherical
particles have the most focused spectrum because they have a single, narrow
primary
peak that allows for optimization using size and composition changes. However,
it is
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possible to utilize a combination of particles of other shapes in order to
develop a
desired filter spectrum. One may broaden the extinction spectrum of a 40 nm
spherical
nanoparticle filter by simply introducing, for example, cubic nanoparticles or
octahedral nanoparticles of an equivalent size.
[00132] In contrast, the attenuation curve of a core-shell nanoparticle may be
tuned
by altering the relative thicknesses of the core and shell. By way of example,
decreasing
the thickness of an Ag shell relative to the size of a SiO2core may reduce the
full width
half maximum of the attenuation spectrum. Shapes of these particles may be
spherical,
ellipsoidal, otherwise shaped, or combinations thereof The shape of the
particles may
also affect the shape and amplitude of the attenuation curve. In an
embodiment, the
optical filter comprises spherical core-shell nanoparticles. In a further
embodiment, the
spherical core-shell nanoparticles have an Ag shell and a Si core. In a yet
further
embodiment, the spherical Ag/Si core-shell nanoparticles have an Ag shell with
a radial
thickness of 45nm and a Si core with a radius of 15nm.
[00133] FIG. 23 depicts a nanoparticle-based optical filter used in
conjunction with
a multilayer thin film filter to form a composite filter 2300. A first filter
may attenuate
light in a first range of wavelengths, thereby substantially reducing or
removing those
wavelengths in the light spectrum entering the second filter. In the depicted
embodiment, ambient light 2302 may enter a filter comprising nanoparticles
2304 that
may be disposed on or embedded in a host medium 2306 that is disposed on a
surface
of the thin film filter 2308. Alternatively or in addition, a thin film filter
and a
nanoparticle-based filter may be disposed on opposing surfaces of a substrate,
such as
the lenses of eyeglasses. In another embodiment, nanoparticles may be embedded
within a thin film filter, and one or more layers of the thin film may be the
host medium
for the nanoparticle-based filter. The ambient light 2302 that enters host
medium 2306
with nanoparticles 2304 embedded therein may be sunlight. The attenuated light
2310
that enters the thin film filter 2308 may have a reduced amount of light in
the range
attenuated by the nanoparticles 2304. The filtered light 2312 that exits the
composite
filter 2300 may be attenuated in two ranges of wavelengths. Similarly, a
"double notch"
filter may be implemented entirely through the use of multi-layer thin film
coatings.
[00134] FIG. 24 illustrates an embodiment of a method 2400 of manufacturing a
composite optical filter for reducing the frequency and/or severity of
photophobic
responses. The method 2400 may be used to design at least one embodiment of a
composite filter described herein. The method 2400 may include determining the
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appropriate light spectrum, as illustrated by act 2402. 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.
[00135] A first light dose to be experienced by the subject may be determined
(using,
for example, Equation 1), as illustrated by act 2404. A second light dose to
be
experienced by a human eye at a wavelength at about 620nm may be estimated
(using,
for example, Equation 12), as illustrated by act 2406. A third light dose to
be
experienced across the visual response spectrum may be determined (using, for
example, Equation 13), as illustrated by act 2408. An optical filter may be
designed
and manufactured using the first light dose, the second light dose, and the
third light
dose, as illustrated by act 2410. The first light dose and the second light
dose may each
be used with the third light dose to determine a figure of merit (FOM) for
each 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.
[00136] FIG. 25 illustrates an embodiment of a method 2500 using a composite
filter
for reducing the frequency and/or severity of photophobic responses or for
modulating
circadian cycles. The method 2500 may be used in conjunction with at least one
embodiment of a composite filter described herein. The method 2500 may include
receiving an amount of light, as illustrated by act 2502. The light received
may include
direct or indirect light from one or more light sources. A first amount of
light that is
attenuated preferentially across the action potential spectrum of the
melanopsin cells
may be transmitted, as illustrated by act 2504. A second amount of light that
is
attenuated preferentially in a wavelength range at about 620nm may be
transmitted, as
illustrated by act 2506. A third amount of light may then be transmitted to a
human
eye, as illustrated by act 2508. 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.
[00137] Efficacy testing has been conducted verifying the benefits of
attenuating
light near about 480nm and 620nm. Preliminary testing included a prospective,
double-
masked, crossover clinical study to determine the efficacy of customized, thin
film
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spectacle coatings in the treatment of chronic migraine. Subjects wore two
different
spectacles during the trial: one coating was a notch filter at 480nm. The
other coating
was a notch filter at 620nm. Typical transmission spectra of gray tinted
lenses with the
different coatings used in this study are shown in Figs. 23A and 23B. The
480nm notch
filter shown blocks about 68% of light absorption by melanopsin, and blocks
42% of
visible light. The 620nm notch filter shown blocks about 66% of light
absorption
centered at 620nm with a ¨55nm width and blocks about 42% of visible light.
The
480nm filters used in the study had average blocking around 480nm of 68 6% and
average visible blocking of 44 4%. The 620nm filters used in the study had
average
blocking around 620nm of 67 2% and average visible blocking of 43 4%. Neither
the
subjects nor the clinical coordinators were informed which lenses had a 480nm
notch
filter and which had a 620nm notch filter. Subjects in the study had to carry
a diagnosis
of chronic migraine, meaning that they have at least 15 headache-days per
month.
Individuals with at least 15 headache-days per month are considered the most
severely
affected migraine patients.
[00138] To assess the efficacy of the intervention, the 6-question "Headache
Impact
Test" ("HIT-6") was chosen as the primary outcome measure. The HIT-6 is a 6-
question instrument that has been designed and validated to assess the impact
of
headaches on a person's life. The score is a continuous variable that ranges
from a
minimum of 36 to a maximum of 78. A score less than 50 indicates that
headaches are
having little impact on one's life, a score of 50-55 indicates "some impact,"
a score of
56-59 indicates "substantial impact," and a score over 60 is consistent with a
"very
severe impact" of headaches.
[00139] Subjects first completed a four-week "pre-wash" during which no study
lenses were worn. This period helped establish base-line characteristics of
their
headaches. Subjects were randomized to wear either one or the other lens
first, utilizing
block randomization. They were instructed to wear the spectacles full-time for
two
weeks. They then had a two-week "washout" period during which no study lenses
were
worn. The subjects then wore the other lens for another two-week period.
Finally,
subjects underwent a final "post-wash" period during which no study lenses
were worn
to establish an exit "finish line" for headache characteristics.
[00140] There is a considerable amount of variability in the frequency and
severity
of headaches. In some cases, this variability may occur even in the same
patient. The
"pre-wash" and "post-wash" periods were added to due to the variability. These
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additional periods, during which no study lenses are worn, minimized the
effect of
"baseline drift" in the study subjects.
[00141] The HIT-6 questionnaire was administered before the study and after
each
of the period of the study, resulting in six completed questionnaires for each
subject.
The study included forty-eight participants initially, and thirty-seven of the
participants
completed the course of the study. Of the thirty-seven subjects who completed
the
study, the baseline HIT-6 score was 64.5. Thirty-three of the thirty-seven
subjects
(89%) had baseline HIT-6 scores greater than or equal to 60. According to the
HIT-6
interpretation, these thirty-three subjects have headaches that are having a
"very severe
impact" on their lives. Both the 480 nm and 620 nm filter lenses displayed a
statistically
significant reduction in HIT-6 values.
[00142] Of the thirty-seven participants that completed the study, nine
subjects were
able to move out of the "very severe impact" HIT-6 category while wearing the
480 nm
lenses; five subjects were able to move out of this category wearing the 620
nm lenses
and five subjects were able to move out of this category wearing either of the
lenses.
Ten subjects experienced at least a 6-point improvement in HIT-6 when wearing
the
480 nm lenses, ten subjects experienced at least a 6-point improvement in HIT-
6 when
wearing the 620 nm lenses and three subjects experienced at least a 6-point
improvement in HIT-6 when wearing either of the lenses. This analysis
indicates that
wearing either the 480 nm or 620 nm spectacle lenses resulted in statistically
significant
reductions in HIT-6. However, there was no significant difference comparing
the effect
of the 480 nm lenses to the 620 nm lenses (p=0.195)...
[00143] Secondary outcomes gleaned from the diaries, including percent days
with
severe headache, percent days where activity had to be changed or subject had
to go to
bed, and percent days requiring an abortive medication, behaved similar to the
primary
outcome for either the 480 nm or 620 nm spectacle lenses: Subjects experienced
significant reductions in these parameters wearing either the 480 nm or 620 nm
lenses.
There was no significant difference comparing the effect of the 480 nm lenses
to the
620 nm lens for any of these three outcomes.
[00144] The melanopsin of the melanopsin ganglion cells is a bistable pigment.
Melanopsin may undergo an isomerization during exposure to light at certain
wavelengths. FIG. 27 is a graph 2700 schematically depicting the cyclic
isomerization
of a bistable pigment as the pigment is exposed to different wavelengths of
light. The
bistable pigment may have first isoform that exhibits a first absorption
spectrum 2702.
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The first absorption spectrum absorbs a first wavelength 2704. The first
isoform of the
bistable pigment may react with the first wavelength 2704. The first
wavelength 2704
may isomerize the bistable pigment and may trigger a phototransduction cascade
in an
associated cell or membrane. In an embodiment, the bistable pigment may be
melanopsin and exposure to a first wavelength 2704 may trigger a
phototransduction
cascade in the melanopsin ganglion cell. Exposure to the first wavelength may
cause
the bistable pigment to isomerize from the first isoform to a second isoform.
The first
isoform may be an active 11-cis isoform of melanopsin. The second isoform may
be
an inactive metamelanopsin isoform. The isomerization of the active 11-cis
isoform
may lead to the phototransduction cascade.
[00145] The second isoform may exhibit a second absorption spectrum 2706. The
second absorption spectrum 2706 may absorb a second wavelength 2708. The
second
isoform of the bistable pigment may react with the second wavelength 2708. In
an
embodiment, the first isoform may be an active isoform of the bistable pigment
and the
second isoform may be an inactive isoform of the bistable pigment. In another
embodiment, the first isoform may be an inactive isoform of the bistable
pigment and
the second isoform may be an active isoform of the bistable pigment. In yet
another
embodiment, the first isoform may be an active isoform of melanopsin and the
second
isoform may be an inactive isoform of melanopsin.
[00146] FIG. 28 depicts a graph 2800 of an active absorption spectrum 2802 and
an
inactive absorption spectrum 2804 for melanopsin. The active absorption
spectrum
2802 and inactive absorption spectrum 2804 each correspond to an active
isoform of
melanopsin and an inactive isoform of melanopsin, respectively. "Active" and
"inactive" should be understood as referring to the physiological activity of
the pigment
.. and the pigment's ability to contribute to photophobic responses in an
individual rather
than the pigment's ability to absorb light. The active absorption spectrum
2802 may
have a maximum at approximately 484 nm. The inactive absorption spectrum 2804
may have a maximum at approximately 587 nm.
[00147] The inactive isoform of melanopsin may absorb wavelengths 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 inactive isoform
to the
active form of melanopsin. The active form of melanopsin may contribute to a
photophobic response of an individual. In at least one embodiment, an
attenuation of
light absorbed by the inactive isoform may disrupt the isomerization of
melanopsin and
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reduce symptoms of light sensitivity in some people, such as pain or
discomfort in
response to light, and the frequency and/or severity of migraine and other
headaches,
and may also prove effective for some in the treatment of blepharospasm, post-
concussion/TBI syndrome, sleep disorders, epilepsy.
[00148] In addition to regulating the exposure of melanopsin ganglion cells to
light
near 480nm and/or 620nm, the attenuation of light at the absorption maximum of
the
inactive absorption spectrum for the inactive isoform of melanopsin may also
yield
improvements in alleviating symptoms associated with light sensitivity. For
example,
an optical filter centered at a wavelength of about 590nm may attenuate the
light
absorbed by the inactive isoform of melanopsin.
[00149] In one embodiment, improvements may be realized by attenuating light
between about 560nm and about 620nm. In another embodiment, improvements may
be realized by attenuating light between about 570nm and about 610nm. In yet
another
embodiment, improvements may be realized by attenuating light using a filter
substantially centered at a wavelength of 590nm with a full-width at half-
maximum of
about 50nm.
[00150] Additionally, a filter may attenuate light wavelengths in multiple
ranges.
For example, an embodiment of a filter may attenuate light absorbed by the
inactive
isoform of melanopsin and light absorbed by the active isoform of melanopsin.
In an
embodiment, a filter may attenuate light at about 590nm in addition to
attenuating light
at about 480nm. In another embodiment, a filter may preferentially attenuate
light
wavelengths from about 450nm to about 510nm and from about 560nm to about
620nm.
In yet another embodiment, a filter may attenuate light between about 470 and
about
490 and between about 580nm and about 600nm.
[00151] Similarly to the previously described 480nm filter and the 620nm
filter, an
optical filter capable of attenuating 590nm light may comprise a high pass
filter, a low
pass filter, an optical notch filter, or combinations thereof The optical
notch filter may
comprise a plurality of layers of dielectric materials, nanoparticles
distributed on or
embedded in a host medium, or a combination thereof In addition, any of the
aforementioned combinations may be used in conjunction with a dye incorporated
in a
substrate. By way of example, producing short pass or notch filters may
include using
alternating layers of high and low refractive index materials. Example low
index
dielectric materials include MgF2 and 5i02. Example high index materials
include
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metal oxides such as TiO2, Ti305, ZrO2, and Ta205, and Si3N4. Numerous other
suitable
materials can be used, including polymer layers.
[00152] Similarly to the embodiments that are intended to attenuate
wavelengths
absorbed by the active isoform of melanopsin and were described previously, an
optical
filter designed to attenuate wavelengths at about 590nm may be manufactured
according to a similar FOM. The light dose D received at about 590nm can be
written
D ree,590 ¨ WR 590 (15)
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 R590 is
the idealized response spectrum at about 590nm, which may be estimated as a
Gaussian
function centered at 590nm with a full-width at half-maximum of 50, 55, or 60
nm,
although other values are anticipated and may prove therapeutic. For
generality, it is
assumed that L=1 so as not to limit discussion to any specific light source,
however
analyses may be performed for any light source of known spectrum.
[00153] A similar dose can be calculated in association with the visual
response
spectrum
Dv, L(zi)T(zi)V(1)dzi.
(16)
where V represents the normalized visual response spectrum.
[00154] The
effect of an optical filter, such as a nanoparticle notch filter, is to reduce
the dose, as described by taking the ratio of dose calculated with the filter
to dose
without the filter, for example
Drec,590
Nr ec, 5 9 0 = _______________________
Drec 590(T =1)
[00155] The "attenuation" of the dose may be written as, for example,
Drec 590
Arec,590 1 Alrec,590 1 n
-"rec 590 (T
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[00156] An FOM can also be defined which compares the blocking of the light at
about 590nm to the blocking of the visual response spectrum
1 Drec 590
FOM = Drec 590(1 1)
Dvis
1
Dv,s(T =1)
(17)
which represents the ratio of the attenuation of light at about 590nm 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 590nm, the
comparison becomes more stringent as a smaller full width half maximum value
is used.
For example, when R(2), the Gaussian distribution used in the estimate, has a
full width
half maximum of 50nm describes a more specific optical filter than that when
the
to estimate includes an R(2) having a 60nm full width half maximum.
[00157] FIG. 29 depicts a method 2900 for reducing symptoms associated with
photophobic responses. The method 2900 includes receiving 2902 light and
attenuating
a first wavelength 2904 and, optionally, a second wavelength 2906. The
attenuation of
the first wavelength may then disrupt the bistable pigment cycle 2908
described in
relation to FIG. 27. In an embodiment, the first wavelength may be determined
by a
maximum of an active absorption spectrum or an inactive absorption spectrum of
a
bistable pigment. In another embodiment, the first wavelength may be
determined by
the maximum of the active absorption spectrum 2802 of melanopsin or maximum of
the inactive absorption spectrum 2804 described in relation to FIG. 28. In yet
another
embodiment, the first wavelength may be 480 nm. In a further embodiment, the
first
wavelength may be 590 nm.
[00158] Attenuating a wavelength should be understood to mean preferentially
attenuating the wavelength or a range including the wavelength as compared to
other
portions of the visible spectrum. For example, attenuating a 590nm wavelength
may
include transmitting less light at or about the 590nm wavelength than other
light in the
visible spectrum. In another example, attenuating a 590nm wavelength may
include
blocking substantially all light at or about the 590nm wavelength and
transmitting other
light in the visible spectrum.
[00159] Attenuating the second wavelength 2906 may include attenuating a
portion
of a second wavelength different from the first wavelength attenuated. In an
embodiment, the second wavelength may be determined by a maximum of an active
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absorption spectrum or an inactive absorption spectrum of a bistable pigment.
In
another embodiment, the first wavelength may be determined by the maximum of
the
active absorption spectrum 2802 of melanopsin or maximum of the inactive
absorption
spectrum 2804 of melanopsin described in relation to FIG. 28. In yet another
embodiment, the first wavelength may be 480 nm. In a further embodiment, the
first
wavelength may be 590 nm.
[00160] Attenuating a first wavelength 2904 and, optionally, attenuating a
second
wavelength 2906 may disrupt a bistable pigment cycle. Attenuating a first
wavelength
2904 may inhibit the isomerization of the bistable pigment from a first
isoform to a
second isoform. The first isoform may be an active isoform or an inactive
isoform.
Attenuating a second wavelength 2906 may inhibit the isomerization of the
bistable
pigment from the second isoform back to the first isoform.
[00161] An optical filter capable of attenuating light at or about a 590 nm
wavelength
may be manufactured and/or tuned by any of the aforementioned processes such
that a
low pass filter, a high pass filter, or an optical notch filter preferentially
attenuates 590
nm light. The filter may include dielectric multi-layers, embedded
nanoparticle
coatings, a color filter, tint, resonant guided-mode filter, a rugate filter,
and any
combination thereof The filter may also include embedded nanoparticle coatings
such
as 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.
[00162] Because
the optical filters of the present disclosure filter out certain colors
of the visible spectrum, there may be the appearance of coloration when
viewing
through the filters. A standard way of quantifying this coloration is using
the CIE
chromaticity diagram, typically referring to the 1931 Standard Observer, but
other
versions of the CIE color space can be used (such as the 1964 10 chromaticity
coordinates, or coordinates based upon Stiles & Burch data, etc., which
produce
substantially similar results), in which two chromaticity coordinates 'x' and
'y' map to
human color perception. There exists a point on the CIE chromaticity diagram,
called
the achromatic point (in which x=y=1/3) in which the perceived color is white
(or gray,
depending upon the transmitted brightness, or luminance, level Y). Ideally, an
optical
filter for viewing would have chromaticity coordinates x=y=1/3.
[00163] Calculation of the chromaticity coordinates is accomplished via color-
matching functions (CMF), which are based upon physiological response to
different
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wavelengths of light. Again, CMFs typically refer to the 1931 2 data, but
other CMFs
can be used (such as the 1964 100 color matching functions, or CMFs based upon
Stiles
& Burch data), which produce substantially similar results. The following
functions can
serve as weighting factors for an input spectrum:
X = f L ()tO ()t) X ()t) d (18)
Y = f MY (A) d (19)
Z = f L (A)T (A) Z (A) d (20)
where X, Y and Z are known as the tristimulus values, L is the light spectrum
(in terms
of intensity, power, photons/sec, etc), T is the spectral transmission of a
filter lying
to between the light source and a person's eye, and X, Y and Z are the
color matching
functions. The 1931 CMFs are plotted in FIG. 30. L may be a standard
illuminant, such
as D50 or D65 for daylight, or represent the spectrum of a specific artificial
light source
such as incandescent (A), fluorescent (series F), LED (series L), etc., but it
can be
assumed that L=1 (e.g. Illuminant E) without loss of generality, although any
valid
function L can be used.
[00164] The chromaticity coordinates may then be calculated from the
tristimulus
values:
X
x =X+ Y+Z
z= 1 ¨ x ¨ y
where only x and y are necessary.
[00165] As an example, the FIG. 31 shows a 480 nm notch filter according to
the
present disclosure, along with the products T (A) X (A) , T (2.)Y (A) , and T
(A) Z (A) , which
represent the color matching functions as modified by the presence of the
filter. The
tristimulus values for this filter are X=94.8, Y=92.4 and Z=58.4, with
corresponding
chromaticity coordinates x=0.386 and y=0.376. Based upon the chromaticity
diagram,
this maps to a yellow color, meaning that the filter will modify normal color
vision with
a yellow hue.
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[00166] By adding a second notch at a wavelength near 590 nm, the chromaticity
coordinates of the filter can be adjusted towards the achromatic point, and
therefore
causing the filter to appear gray. One such embodiment is shown in FIG. 32,
where the
480 nm and 590 nm notches are approximated as Gaussian functions (center
wavelengths 480nm and 590nm, respectively; full-widths at half-maxima of 31 nm
and
50 nm; notch depths of .625 and 0.41; and an overall 10% uniform reduction
across the
visible spectrum to represent a light gray tint, which reduces the overall
transmittance
but does not affect the chromaticity coordinates).
[00167] The 480 nm notch alone has tristimulus values X=91.8, Y=89.9, and
Z=68.5, with chromaticity coordinates x=0.367 and y=0.359, again, producing a
yellow
hue. The addition of the 590 nm notch nearly equalizes the tristimulus values
at X=68.1,
Y=68.4, and Z=68.2, with chromaticity coordinates x=0.3327 and y=0.3341,
nearly
achieving the achromatic condition.
[00168] Numerous other combinations are possible, based upon adjusting the
widths, depths, shapes, and positions of the two notches. For instance, since
blocking
light near 480 nm and 590 nm wavelengths is known to reduce light sensitivity
and
migraine, one filter design procedure is to first design a therapeutic 480nm
notch (i.e.
designed to achieve a certain amount of blocking across the melanopsin action
potential
spectrum Rmelan or wavelength range, or to achieve a certain FOM, as taught by
the
present disclosure), then add a second notch at about 590 nm in order to
achieve the
desired achromatic condition. Again, using a simplified Gaussian notch filter
at 480 nm
center of full-width at half-maximum 52 nm and depth 0.625, a color balancing
notch
of 584 nm center, 51 nm width, and 0.57 depth could be used to achieve
chromaticity
coordinates x=0.3332 and y=0.338.
[00169] In another embodiment, a color balancing notch at about 587 nm, width
67nm, and depth 0.47 could be used to achieve x=0.3323 and y=0.3340. Other
filter
design procedures can be envisioned, such as first designing a 590 nm
therapeutic notch
(i.e. designed to achieve a certain amount of blocking across the R590
response function
or wavelength range, or achieve a certain FOM, as taught by the present
invention) and
color balancing with a second notch at about 480 nm; designing notches at both
480 nm
and 590 nm and adjusting the widths and depths to simultaneously approach the
desired
achromatic condition and achieve a certain amount of cumulative light blocking
across
both the Rmelan and R590 response functions or a certain FOM taking blocking
within
and outside these regions into account.
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[00170] The terms "approximately," "about," "near," and "substantially" as
used
herein represent an amount close to the stated amount that still performs a
desired
function or achieves a desired result. For example, the terms "approximately,"
"about,"
and "substantially" may refer to an amount that is within less than 10% of,
within less
than 5% of, within less than 1% of, within less than 0.1% of, and within less
than 0.01%
of a stated amount.
[00171] It should be noted that, while the 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 particular forms set forth, but on the contrary,
these
to descriptions
are intended to cover such alternatives, modifications, and equivalents as
may be included within the scope of the invention. Any elements of the above-
described embodiments may be combined with any other elements of the above-
described embodiments. For example, any of the above-described methods of
manufacture or methods of light attenuation may be combined with the described
optical filters and associated wavelengths. 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.
