Patent Description:
A large number of people have Dry Eye Disease ("DED"), which includes symptoms of intense pain, stinging eyes, foreign body sensation, light sensitivity, blurriness, increased risk of infection, and possible vision loss. DED is characterized by insufficient tear volume or unbalanced tear composition on the ocular surface of a patient, which is generally caused by insufficient tear production or excessive tear evaporation. Insufficient tear volume results in tear hyperosmolarity, which causes inflammation and nerve damage and can lead to progressive loss of tear production and quality.

Dry-eye symptoms vary based on a variety of factors. For example, dry-eye symptoms vary throughout a day in response to diurnal physiological variations in tear pH, intraocular pressure, corneal sensitivity, visual sensitivity, and melatonin production. For instance, corneal sensitivity is often significantly greater in the evening than compared to the morning. Longer term variations in dry-eye symptoms can be related to use of systemic medications, chronic disease (e.g., diabetes), hormonal changes, and aging. Changes to a patient's environment also contribute to dry-eye symptom variations. For example, dry-eye symptoms can increase due to low humidity of air-conditioned offices, winter heating, computer use, phone use, allergens, and contact lenses.

Some current approaches to treating dry-eye symptoms may not account for the variety of factors that impact the severity and onset of the symptoms, as current treatment for DED is primarily eye drop-based and may provide limited episodic or temporary relief.

Prior art is disclosed by <CIT>, <CIT>, and <CIT>.

The present disclosure describes devices for treating dry eye. According to some aspects, a device is presented that is configured to be positioned underneath an eyelid and worn by a user for treating dry eye. The device includes a first surface configured to face a portion of a bulbar conjunctiva and/or sclera of the eye, and a second surface configured to face the palpebral conjunctiva and/or eyelid. The device further includes a plurality of stimulation electrodes proximal to the first surface, wherein the plurality of stimulation electrodes is configured to stimulate the sclera and/or the bulbar conjunctiva. The electrodes include a plurality of electrode prongs or branches defined by a plurality of slots extending into the electrode regions. The device further includes an antenna and other electronic components to convert electromagnetic energy received from a wireless remote control device into a current and/or voltage to supply power to the plurality of stimulation electrodes. The slots provide a discontinuous or interrupted surface pattern which inhibits the formation of lossy electrical eddy currents in the electrodes to facilitate or promote near-field coupling with the wireless remote control device.

According to the invention as defined by claim <NUM>, a device is provided that is configured to be located underneath an eyelid and worn by a user for treating dry eye. The device includes: a flexible substrate; an antenna disposed on a first side of the substrate and configured to receive electromagnetic energy from a transmitter; one or more electronic components disposed on the first side of the substrate; and a first electrode and a second electrode, the first and second electrodes disposed on a second side of the substrate opposite the first side. In some aspects, each of the first electrode and the second electrode comprises an electrode surface and a plurality of slots in the electrode surface defining a plurality of electrode prongs, where the plurality of slots facilitate near-field coupling between the transmitter and the antenna. In a further aspect, the one or more electronic components are in communication with the antenna, the first electrode, and the first electrode, and the one or more electronic components are configured to provide electrical power to the first electrode and the second electrode.

In some embodiments, the antenna and the one or more electronic components are configured to convert electromagnetic energy into the electrical power. In some embodiments, the one or more electronic components comprises a rectifier. In some embodiments, the one or more electronic components comprises an application-specific integrated circuit (ASIC). In some embodiments, the one or more electronic components comprises one or more discrete surface mount electronic components. In some embodiments, the first electrode comprises a first plurality of electrode prongs, wherein the second electrode comprises a second plurality of electrode prongs, and wherein the first plurality of electrode prongs and the second plurality of electrode prongs extend in opposing directions. In some embodiments, the first plurality of electrode prongs and the second plurality of electrode prongs extend toward a central axis of the flexible substrate. In some embodiments, the first plurality of electrode prongs and the second plurality of electrode prongs extend away from a central axis of the flexible substrate.

In some embodiments, each of the electrode prongs comprises a first width, and wherein each of the slots comprises a second width that is less than the first width. In some embodiments, the first electrode and the second electrode are spaced from each other on the second side of the substrate. In some embodiments, the device further includes an insulating layer disposed on the first side of the substrate, the insulating layer insulating and sealing the antenna. In some embodiments, the antenna comprises a first metallic trace arranged in a spiral. In some embodiments, the antenna defines an antenna region, and wherein the first and second electrodes are juxtaposed on the antenna region. In some embodiments, the first electrode and the second electrode comprise a second metallic trace, and wherein the second metallic trace is insulated from the first metallic trace by the substrate.

According to another embodiment of the present disclosure, a device is provided that is configured to be located underneath an eyelid and worn by a user for treating dry eye. The device includes: a flexible substrate; an antenna trace disposed on a first side of the substrate and configured to receive electromagnetic energy from a remote control device, the antenna trace comprising at least one loop surrounding and defining an antenna region; electronic circuitry electrically coupled to the antenna trace; and a first electrode trace and a second electrode trace electrically coupled to the electronic circuitry, wherein the first and second electrode traces are disposed on a second side of the substrate opposite the first side. In some aspects, each of the first electrode trace and the second electrode trace comprises an electrode surface and a plurality of slots in the electrode surface defining a plurality of electrode branches, wherein the plurality of slots promote near-field coupling between the remote control device and the antenna trace. In a further aspect, the first electrode trace and the second electrode trace are juxtaposed with the antenna region.

In some aspects, the first electrode trace comprises a first plurality of electrode branches extending in parallel. In some aspects, at least a portion of the first electrode trace overlaps with at least a portion of the antenna trace. In some aspects, the device further includes an elastomeric material encapsulating at least the substrate, the electronic circuitry, and the antenna trace. In some aspects, the substrate comprises a bean shape, and wherein device is configured to curl along at least a first axis.

Disclosed herein are devices for placement underneath the eyelid, and in particular within a patient's fornix, which is a space between the eyelid and the eye. More specifically, the devices described herein may be configured to be positioned between, and directly contacting, the palpebral conjunctiva, and the bulbar conjunctiva. The devices include one surface for facing the eyelid (e.g., palpebral conjunctiva) and another surface for facing the eye (e.g., the sclera and/or the bulbar conjunctiva). In some embodiments, the devices include electrodes configured to stimulate the sclera and/or the bulbar conjunctiva to induce tear production. The devices may be configured to induce electrical currents into the eye tissue or other tissue of the patient at different depths, intensities, and/or frequencies. It may be advantageous for the devices disclosed herein to have relatively small footprints to fit within the confined spaces available within the eyelid, to be flexible and thin to enhance patient comfort, and to generate sufficient voltage and/or current to stimulate the patient's nerve and achieve a desired physiological response.

<FIG> is a perspective view of a therapeutic device <NUM> configured to be worn underneath a patient's eyelid (e.g., in the fornix) for stimulating nerves in and/or around the patient's eye. The device <NUM> is flexible along at least one axis and is sized, shaped, and otherwise configured to be worn inside the patient's eyelid, as shown in <FIG>. Referring again to <FIG>, the device <NUM> includes electrodes <NUM>, <NUM> configured to stimulate nerves in and around the patient's eye, which may cause or enhance tear production, or other physiological responses to treat dry eye or other ophthalmic conditions.

The device <NUM> includes a first electrode <NUM> and a second electrode <NUM> disposed on a substrate <NUM>. An antenna <NUM> is disposed on opposing side of the substrate <NUM> and is configured to receive electromagnetic energy from a wireless device (e.g. remote control <NUM> shown in <FIG>), and to harness the electromagnetic energy to produce electrical power for the components of the device <NUM>. Electronic components <NUM> are also attached to the substrate <NUM> and in electrical communication with the antenna <NUM> and the electrodes <NUM>, and <NUM>.

The substrate <NUM> may include a flexible polymer material, such as a liquid crystal polymer (LCP), a polyamide (e.g., KAPTON®), or any other suitable type of substrate. The substrate <NUM> is configured to bow, bend, or flex along at least one axis, and is configured to electrically isolate the electrical components (electrodes <NUM>, <NUM>, antenna <NUM>) from one another. The substrate <NUM> may include a single layer of material, or multiple layers of a same material or of different materials. For example, in some embodiments, the substrate <NUM> includes at least two layers of a polymer material, with the antenna <NUM> disposed between two of the layers of material. The substrate <NUM> provides sufficient electrical isolation for the variety of electronic components <NUM>, the electrodes <NUM>, <NUM>, and the antenna <NUM>.

The first electrode <NUM> comprises a plurality of electrode prongs <NUM> (which may also be referred to as electrode fingers or branches) separated or defined by a plurality of slots <NUM>. The slots <NUM> extend from an outer region or boundary of the electrode <NUM> towards an inner or central portion of the electrode <NUM>, where the prongs <NUM> are electrically connected by an electrode spine <NUM>. Similarly, the second electrode <NUM> comprises a plurality of electrode prongs <NUM>, where the electrode prongs <NUM> are separated or defined by a plurality of slots <NUM>. The slots <NUM> extend from an outer region or boundary of the electrode <NUM> towards an inner or central portion of the electrode <NUM>, where the prongs <NUM> are electrically connected by an electrode spine <NUM>. The electrodes <NUM>, <NUM> are each in electrical communication with the electronic components <NUM> and the antenna <NUM>, but may be otherwise electrically isolated from one another.

In some aspects, the first electrode <NUM> and the second electrode <NUM> may be described as including electrode surfaces defined by the outline or footprint of each electrode <NUM>, <NUM>. In this regard, the slots <NUM>, <NUM> may be referred to as extending into each respective electrode surface. In the illustrated embodiment, the electrodes <NUM>, <NUM> are oriented such that the electrode prongs <NUM>, <NUM> extend outward in opposing directions away from a central axis of the substrate <NUM>. However, as will be further explained below, the electrodes <NUM>, <NUM> may be oriented such that the electrode prongs <NUM>, <NUM> extend inward in opposing directions toward the central axis of the substrate <NUM>. In other embodiments, the electrode prongs <NUM>, <NUM> may extend in parallel toward a top side of the device <NUM>, or a bottom side of the device. In other embodiments, the electrode prongs <NUM>, <NUM> extend in a same direction, such as to the right or to the left.

The electrodes <NUM>, <NUM> may be sized and shaped to occupy a significant portion of the footprint of the loop antenna <NUM>. This regard, it may be advantageous for each electrode <NUM>, <NUM> occupy a relatively large portion of the total surface area of the device <NUM>. In this regard, stimulation of the nerves may be improved by greater contact areas of the electrodes <NUM>, <NUM> and the patient's tissue/nerves. However, a large conductive surface overlapping with the antenna <NUM> may interfere with the antenna's <NUM> ability to harness electromagnetic (EM) energy wirelessly to provide to the electrodes <NUM>, <NUM> and other electronic components <NUM> of the device <NUM>. For example, electrical eddy currents may result from electromagnetic energy fields passing through the antenna <NUM>. However, the slots <NUM>, <NUM> reduce, limit, or eliminate the formation of eddy currents such that the antenna <NUM> can more efficiently harness electrical power for the components of the device <NUM>. The slots <NUM>, <NUM> may be wider or narrower than what is shown in the embodiment of <FIG>. However, it may be advantageous for the slots <NUM>, <NUM> to be very narrow (e.g., <NUM> - <NUM>) to maintain a proportionally high surface area for each electrode <NUM>, <NUM>. Accordingly, the slots and prongs configuration of the electrodes <NUM>, <NUM> promote near-field coupling between the device <NUM> and a wireless remote control device (e.g., <NUM>, <FIG>).

The slots <NUM>, <NUM> may extend into the electrode regions of the electrodes <NUM>, <NUM> by a greater or lesser amount than what is shown in <FIG>. Further, although the slots <NUM>, <NUM> are shown as straight and parallel to one another, it will be understood that the slots <NUM>, <NUM> may have arcuate profiles, zigzag profiles, curved profiles, non-parallel profiles, or any other suitable shape. Further, the electrodes <NUM>, <NUM> may define shapes or footprints other than what is shown. For example, each electrode may define a circular, or roughly circular electrode region, with the slots <NUM>, <NUM> extending into the respective electrode regions. In other embodiments, the electrodes <NUM>, <NUM> may define rectangular regions, elliptical regions, bean-shaped regions, triangular regions, hexagonal regions, or any other suitable shape. In some embodiments, the electrodes <NUM>, <NUM> overlap with the antenna <NUM> by a greater or lesser extent than what is shown in <FIG>. For example, one or both of the electrodes <NUM>, <NUM> may overlap an entirety of the loop antenna <NUM> in at least one direction (e.g., width). In other embodiments, one or both of the electrodes <NUM>, <NUM> may be sized and shaped to fit entirely within an innermost loop of the antenna <NUM>, such that no portion of the electrodes <NUM>, <NUM> overlaps with any portion of the antenna <NUM>. In other embodiments, one or both of the electrodes <NUM>, <NUM>, may extend beyond a footprint of the antenna <NUM> in at least one direction.

The electrodes <NUM>, <NUM> may comprise metallic traces, films, or foils disposed on the substrate <NUM>. For example, the electrodes <NUM>, <NUM> may be disposed on the substrate <NUM> by chemical vapor deposition, sputtering, laser welding, mounting, adhesion, manual fabrication, or any other suitable process. The electrodes <NUM>, <NUM> may include a biocompatible conductive material, such as gold, platinum, iridium, alloys that include gold, platinum, and/or iridium, or any other suitable material. Similarly, the antenna <NUM> may comprise one or more traces of a conductive material, such as gold, platinum, iridium, or alloys thereof. For example, in some embodiments the antenna <NUM> and the electrodes <NUM>, <NUM> comprise a same type of material in other embodiments, the electrodes <NUM>, <NUM> comprise a different material in the antenna <NUM>.

In the illustrated embodiment, the antenna <NUM> includes a spiral of metallic traces having four loops. The four loops may be concentric and non-overlapping such that the antenna <NUM> can be deposited on the substrate <NUM> in a single manufacturing step. However, it will be understood that in other embodiments, the loop antenna <NUM> may differ from what is shown in one or more aspects. For example, the loop antenna <NUM> may include fewer or more loops than what is shown in <FIG>. In some embodiments, the loop antenna <NUM> includes a single loop of metallic material. In some embodiments, the loop antenna <NUM> may include multiple electrically connected traces that are not disposed in a spiral shape. For example, the antenna <NUM> may include distinct concentric loop traces. The antenna <NUM> may occupy a greater or lesser amount of the available surface area on the device <NUM> than what is shown in <FIG>. Further, although the antenna <NUM> defines a kidney or bean shape, it will be understood that the antenna <NUM> may define other shapes, such as elliptical, circular, rectangular, triangular, or any other suitable shape. The antenna <NUM> is disposed on an opposite side of the substrate <NUM> than the electrodes <NUM>, <NUM>. Accordingly, although the electrodes <NUM>, <NUM> overlap with the antenna <NUM>, the electrodes <NUM>, <NUM> are isolated from the antenna <NUM> by the substrate <NUM>.

The device <NUM> includes a plurality of vias <NUM>, <NUM>, <NUM>, which provide points of electrical connection between the electrodes <NUM>, <NUM>, and the electronic components <NUM> and/or the antenna <NUM>, which are disposed on the opposite side of the substrate <NUM> The vias <NUM>, <NUM>, <NUM> may include a hole or aperture extending through the substrate <NUM>, where the walls or interior surfaces defining the aperture are covered by a conductive material, such as hold, platinum, iridium, alloys thereof, or any other suitable conductive material. The electrical connections between the electrodes <NUM>, <NUM>, the electronic components <NUM>, and the antenna <NUM> will be described further below with respect to <FIG>.

The electronic components <NUM> may include or provide an electrical rectifier to modulate the electromagnetic energy provided by the antenna <NUM> into direct current. Further, the electronic components <NUM> may include electronic control components to selectively activate one or both of the electrodes <NUM>, <NUM>. The electronic components <NUM> may be connected to each other, to the electrodes <NUM>, <NUM>, and/or to the antenna <NUM> by one or more conductive traces, filars, or other conductors coupled to or disposed on the substrate <NUM>. In some embodiments, the electronic components <NUM> may be contained or packaged into a single chip, such as an application-specific integrated circuit (ASIC). In some embodiments, the electronic components <NUM> include one or more discrete surface mount components, such as capacitors, resistors, diodes, inductors, transistors, and/or any other suitable discrete surface mount component. In some embodiments, the electronic components <NUM> include one or more ASICs in addition to one or more discrete surface mount components. The electronic components <NUM> may further include electronics that improve or increase the safety of the device. The embodiment shown in <FIG> is configured for battery-less operation in which the device <NUM> is powered solely by a wireless device. Battery-less operation may allow for a smaller and more comfortable form factor. In other embodiments, the device <NUM> may include a battery to allow for occasional nerve stimulation according to a configured schedule stored in a memory of an ASIC.

The device <NUM>, which is configured to be worn under the patient's eyelid, may be configured to stimulate the bulbar conjunctival surface to efferently activate lacrimal gland secretion. Because the nerve density on the bulbar conjunctiva is relatively sparse, it may be advantageous to use electrodes having a relatively large surface area. The device <NUM> allows for larger electrodes to be used without degrading the radiofrequency (RF) coupling and power transfer with the antenna <NUM> for operation of the device <NUM>. As described further below, the device <NUM> may also include a magnetic waveguide backing material to further improve RF power coupling efficiency. The improved efficiency may allow for a handheld remote control device to have a longer lifetime between recharges. Further, lower RF power may be used to operate the device to limit the amount of electromagnetic radiation directed towards the patient. The larger electrodes sizes allow for larger stimulation charge for a given charge density limit, and may cover more nerves (e.g., ciliary nerves) for improved treatment. Moreover, the slotted electrodes <NUM>, <NUM> may allow for the creation of spatial field patterns that can increase the efficacy of nerve stimulation by using spatial field gradients near nerves or cells.

<FIG> is a perspective view of a patient <NUM> wearing a nerve stimulation device <NUM> inside the bottom eyelid below the eye <NUM>. The device <NUM> is being controlled by a remote control device <NUM>, which emits electromagnetic energy <NUM> toward the device <NUM>. In some aspects, the remote control device <NUM> may be referred to as a transmitter or a controller. The remote control device <NUM> is configured to emit the electromagnetic energy <NUM> according to a predefined protocol. The protocol used to emit the electromagnetic energy <NUM> may determine which of the electrodes <NUM>, <NUM> of the device <NUM> is activated, for what amount of time, and/or at what intensity. The remote control device <NUM> may resemble a wireless car key fob or an optical thermometer, in some embodiments. The remote control device <NUM> may be powered by an internal battery, and may be compact and portable such that the patient <NUM> can carry the remote control device <NUM> with her wherever she goes. Accordingly, the patient <NUM> may use the remote control device <NUM> to activate the electrodes <NUM>, <NUM> of the device <NUM> at the onset of dry eye symptoms, for example. In some aspects, the patient <NUM> may use the remote control device 70to activate the device <NUM> according to a predefined or prescribed schedule.

The remote control device <NUM> may be configured to be worn as a necklace in some aspects. In some embodiments, the wireless remote control device <NUM> may include a smart phone device configured with NFC capabilities. In some aspects, the remote control device <NUM> may record usage data, and/or ensure patient safety. In some aspects, the remote control device <NUM> may be configured to run an app that helps with disease management and compliance.

<FIG> shows a top plan view of the device <NUM>. The device <NUM> has a bean shape or kidney shape. The shape of the device <NUM> may correspond to the available space within the patient's fornix, which is the space between the eyelid and the surface of the eye. Further, the shape of the device <NUM> may be selected accounting for curvature of the device <NUM> in at least one axis while being worn by a patient. In some aspects, the bean shape may allow the device <NUM> to conform to the volume available in the fornix, and to conform to the curvature of the cornea to facilitate contact of the electrodes with the bulbar conjunctiva, sclera, and/or the limbus. In some aspects, the device <NUM> may be used to stimulate the limbus, if the electrode separation is sufficient and occupies more of the volume available in the fornix.

A large portion of the footprint of the device <NUM> is occupied by the electrodes <NUM>, <NUM>. A plurality of electronic components <NUM> is disposed in an electronics region <NUM> between the electrodes <NUM>, <NUM>. In other embodiments, the electronics region <NUM> may be positioned below, above, or to the right or to the left of the electrodes <NUM>, <NUM>.

The device <NUM> includes a width <NUM> and a height <NUM>. The width <NUM> height <NUM> and shape of the device <NUM> may define or determine the size, area, or footprint of the device. In this regard, the width <NUM>, height <NUM>, shape, and overall footprint of the device <NUM> is suitable for positioning under the patient's eyelid and within the fornix. For example, the width <NUM> of the device <NUM> may range between <NUM> and <NUM>, and the height <NUM> of the device <NUM> may range between <NUM> and <NUM>. In this regard, the area or footprint of the device <NUM> may range between <NUM><NUM> and <NUM><NUM>. Further, the electrodes <NUM>, <NUM> may occupy, in the aggregate, a substantial portion of the area or footprint of the device <NUM>. For example, the electrodes <NUM>, <NUM>, taken together, may occupy more than <NUM> percent of the total area or footprint of the device. In the illustrated embodiment, the overall size or footprint of the device <NUM> substantially corresponds to the size of footprint of the antenna trace <NUM>. However, in some embodiments, the device has a footprint which is substantially larger than the footprint of the antenna <NUM>. For example, in some embodiments, the regions occupied by the electrodes <NUM>, <NUM> extend past or beyond the antenna region defined by the antenna trace <NUM> in one or more directions. It will be understood that the dimensions and ranges described herein are exemplary only and are not limiting. For example, the device <NUM> may include a width <NUM>, height <NUM>, or other dimension greater or smaller than what is explicitly stated herein.

<FIG> are cross-sectional views of the device <NUM> shown in <FIG>, taken along lines <NUM>-<NUM> and <NUM>-<NUM>, respectively. Referring to <FIG>, the device <NUM> is shown in a curved state after being inserted into the patient's fornix. The electronic components <NUM> are disposed on a palpebral conjunctiva-facing side, which may also be referred to as a posterior side, a back side, or a rear side of the device <NUM> away from the patient's eyeball, and the electrodes <NUM>, <NUM> are on an opposite bulbar conjunctiva-facing side of the device <NUM> such that the electrodes <NUM>, <NUM> are in electrical communication with the eye tissue. The device <NUM> also includes a flexible coating or encapsulant <NUM>, with the substrate <NUM>, electronic components <NUM>, and electrodes <NUM>, <NUM> embedded within and surrounded by the encapsulant <NUM>. The encapsulant <NUM> may comprise a biocompatible elastomeric material, such as a silicone elastomer, hydrogel, silicone hydrogel, or any other suitable biocompatible material. In some embodiments, the encapsulant <NUM> includes an LCP, polyimide, or any other suitable polymeric material. In some embodiments, the electrodes <NUM>, <NUM> are not covered or encapsulated by the encapsulant <NUM> such that the electrodes can make direct physical contact with the patient's eye. In other embodiments, the electrodes <NUM>, <NUM> are covered by or encapsulated in the encapsulant <NUM>, but at least the portion of the encapsulant <NUM> disposed over the electrodes is conductive such that the electrodes <NUM>, <NUM> can stimulate the nerves through the encapsulant <NUM>.

Referring to <FIG>, a cross-sectional view of the device <NUM> is shown without the encapsulant <NUM>. The electrode prongs <NUM> of the second electrode <NUM> are shown disposed on a first side of the substrate <NUM>, and the antenna trace <NUM> is disposed on an opposite second side of the substrate <NUM>, such that the substrate <NUM> electrically insulates the electrode prongs <NUM> from the antenna trace <NUM>. Further, the outer prongs <NUM> overlap the antenna trace region <NUM>, which corresponds to a total width of the antenna trace <NUM> on either side of the loop. In the embodiment of <FIG>, a coating or insulating layer <NUM> is disposed over the antenna trace <NUM> and the second side of the substrate <NUM>. In some embodiments, the coating layer <NUM> is the encapsulant <NUM>. In other embodiments, the coating layer <NUM> comprises a different layer and/or material. For example, the coating layer <NUM> may include an LCP or a polyimide layer bonded to the substrate <NUM>. In this regard, the coating layer <NUM> may include the same material as the substrate <NUM> or a different material.

Further, in the embodiment shown in <FIG>, a magnetic waveguide backing material <NUM> is coupled to a rear side or backside of the insulating layer <NUM>. The magnetic waveguide backing material <NUM> can guide the incident magnetic fields generated by the remote control device (<NUM>, <FIG>) away from the large electrodes <NUM>, <NUM>, resulting in lower power losses in the electrodes <NUM>, <NUM> this may result in improving the efficiency of wireless power linking between the remote control device and the antenna <NUM>. Increase in efficiency due to the magnetic backing material <NUM> may depend on the amount and location of the magnetic material used. Typically, the properties of the ferrite material may be < <NUM> for real permeability and < <NUM> for imaginary permeability at the frequency of interest. It will also be understood that the magnetic waveguide backing material <NUM> may be coupled to the substrate <NUM> and/or the insulating layer <NUM> in a configuration different from what is shown. For example, in some embodiments, the magnetic waveguide backing material <NUM> may be disposed on the opposite second side of the substrate <NUM>, opposite the electrode prongs <NUM>, with the antenna <NUM> and the insulating layer <NUM> disposed over the magnetic waveguide backing material <NUM>. In other embodiments, the magnetic waveguide backing material <NUM> is disposed directly over the antenna <NUM>, and between the substrate <NUM> and the insulating layer <NUM>. In other embodiments, the device <NUM> does not include the magnetic backing material <NUM>. In some embodiments, the magnetic waveguide backing material <NUM> includes a flexible ferrite sheet. The flexible ferrite sheet may include a ferrous material to facilitate magnetic field coupling. One example of a flexible ferrite sheet is a MCP-DS-MHLL Sheet manufactured by Laird Technologies Inc.

<FIG> is a perspective view of a palpebral conjunctiva-facing side of the device <NUM>, which may also be referred to as a rear side, a posterior side, or a back side. In the embodiment shown in <FIG>, the palpebral conjunctiva-facing side of the device <NUM> includes the insulating layer <NUM> positioned over the substrate <NUM> and the electronic components <NUM>. The insulating layer <NUM> may be attached, adhered, deposited, or otherwise coupled to the substrate <NUM> such that the insulating layer <NUM> insulates the electronic components <NUM>. In some embodiments, the insulating layer <NUM> also insulates, covers, and/or seals the antenna trace <NUM> (<FIG>). In other embodiments, the antenna trace <NUM> is insulated by a different insulating layer or substrate layer, and the insulating layer <NUM> is disposed over the different insulating layer or substrate layer.

The electronic components <NUM> are mounted to or deposited on the palpebral conjunctiva-facing side of the device <NUM>. In some aspects, placing the bulging or protruding electronic components <NUM> on the palpebral conjunctiva-facing side of the device <NUM> may improve patient comfort, as the protruding electronic components <NUM> will be positioned away from the patient's eye tissue when the device <NUM> is inserted into the patient's fornix. The insulating layer <NUM> may be heat shrunk, stamped, or otherwise deformed to accommodate the electronic components <NUM> and provide for a more comfortable, or smoother surface. In other embodiments, the electronic components <NUM> are mounted to or deposited on the bulbar conjunctiva-facing side, or front side, of the device <NUM>.

<FIG> is a diagrammatic view of electronic components <NUM> of the therapeutic device, according to an embodiment of the present disclosure. The electronic components <NUM> include capacitors <NUM>, <NUM>, diodes <NUM>, <NUM>, and a resistor <NUM> in electrical communication with the antenna <NUM> and the electrodes <NUM>, <NUM>. In some aspects, the antenna <NUM> shown in <FIG> may be referred to as a loop inductor. The electronic components <NUM> may provide one or more electrical rectifiers configured to convert pulsed RF waves provided by the antenna <NUM> to pulsed electrical energy to power the electrodes <NUM>, <NUM>. For example, the electronic components <NUM> may be configured to provide current pulses or voltage pulses to one or both of the electrodes <NUM>, <NUM>. In some embodiments, the electronic components <NUM> may be configured to provide biphasic pulses. In other embodiments, the electronic components <NUM> are configured to provide monophasic pulses.

It will be understood that the embodiment shown in <FIG> is for illustrative purposes only, and that the electronic components <NUM> may vary from what is shown. For example, in some aspects, the electronic components <NUM> are included in one or more application specific integrated circuits (ASICs) configured to rectify the electrical energy provided by the antenna <NUM>. In other embodiments, the electronic components <NUM> may include fewer or more components than what is shown in <FIG>.

<FIG> are top plan views of nerve stimulating devices <NUM>, <NUM>, <NUM>, <NUM>, according to various embodiments of the present disclosure. In particular, the embodiments shown in <FIG> illustrate nerve stimulating devices according to various electrode prong and spacing configurations. In this regard, the electrodes (e.g., <NUM>, <NUM>) may be positioned close together, or spaced apart. Further, the electrode prongs (<NUM>, <NUM>) may extend outward away from a central axis of the device, or may extend inward toward the central axis of the device.

Referring to <FIG>, the device <NUM> includes electrodes <NUM>, <NUM> mounted on a substrate <NUM>. The electrodes <NUM>, <NUM> comprise respective sets of prongs <NUM>, <NUM> extending away from a central axis of the device <NUM>. In other words, the electrodes <NUM>, <NUM> include slots extending into respective electrode surfaces from the outer boundaries of the electrode surfaces. Further, the electrodes <NUM>, <NUM> may be described as being relatively close to one another with respect to the central axis of the device <NUM>. In some embodiments, the spacing between the electrodes <NUM>, <NUM> may be between <NUM>% and <NUM>% of the width of each electrode <NUM>, <NUM>.

Referring to <FIG>, the device <NUM> includes electrodes <NUM>, <NUM> mounted on a substrate <NUM>. The electrodes <NUM>, <NUM> comprise respective sets of prongs <NUM>, <NUM> extending away from a central axis of the device <NUM>, similar to the device shown in <FIG>. In other words, the electrodes <NUM>, <NUM> include slots extending into respective electrode surfaces from the outer boundaries of the electrode surfaces. Further, the electrodes <NUM>, <NUM> may be described as being relatively spaced apart from one another with respect to the central axis of the device <NUM>. In some embodiments, the spacing between the electrodes <NUM>, <NUM> may be between <NUM>% and <NUM>% of the width of each electrode <NUM>, <NUM>.

Referring to <FIG>, the device <NUM> includes electrodes <NUM>, <NUM> mounted on a substrate <NUM>. The electrodes <NUM>, <NUM> comprise respective sets of prongs <NUM>, <NUM> extending inward toward a central axis of the device <NUM>. In other words, the electrodes <NUM>, <NUM> include slots extending into respective electrode surfaces from the inner boundaries of the electrode surfaces. Further, the electrodes <NUM>, <NUM> may be described as being relatively close to one another with respect to the central axis of the device <NUM>, similar to the device <NUM> shown in <FIG>.

Referring to <FIG>, the device <NUM> includes electrodes <NUM>, <NUM> mounted on a substrate <NUM>. The electrodes <NUM>, <NUM> comprise respective sets of prongs <NUM>, <NUM> extending inward toward a central axis of the device <NUM>, similar to the device <NUM> shown in <FIG>. In other words, the electrodes <NUM>, <NUM> include slots extending into respective electrode surfaces from the inner boundaries of the electrode surfaces. Further, the electrodes <NUM>, <NUM> may be described as being relatively spaced apart from one another with respect to the central axis of the device <NUM>, similar to the device <NUM> shown in <FIG>.

<FIG> illustrate a nerve stimulation device <NUM> according to another embodiment of the present disclosure. In the illustrated embodiment, the device <NUM> includes a first electrode <NUM> mounted on a first side <NUM> of the device <NUM>, and a second electrode <NUM> mounted on an opposite second side <NUM> of the device <NUM>. In some aspects, the first side <NUM> may be a palpebral conjunctiva-facing side, and the second side <NUM> may be a bulbar conjunctiva-facing side. The electrodes <NUM>, <NUM> may be mounted to one or more substrates comprising one or more layers of polymeric material. In particular, the first electrode <NUM> may be mounted on a first substrate layer, with an antenna attached to, coupled to, or mounted on an opposite second side of the first substrate layer. Further, a second substrate layer may be placed over an opposite side of the antenna, with the second electrode <NUM> mounted to the opposite second side of the second substrate layer. Accordingly, the antenna may be positioned between two substrate layers, with the electrode <NUM>, <NUM> mounted to opposite outward-facing sides of the respective substrate layers. Further, electrical circuitry may be positioned between the electrode layers. The device includes a first electrical via <NUM> on the first side <NUM>, and a second electrical via <NUM> on the second side <NUM>. The electrical vias <NUM>, <NUM> may extend through the respective substrate layers to electrically connect the electrodes <NUM>, <NUM> to the electronic components and/or to the antenna trace between the respective substrate layers.

In the embodiment shown in <FIG>, the path of the current created by the electrodes <NUM>, <NUM> disposed on opposite facing sides of the device <NUM> may be more shallow or superficial compared to other electrode configurations (e.g., electrodes <NUM>, <NUM>). Accordingly, the device <NUM> may be more suitable or appropriate for stimulating specific types of nerves which are more superficial. For example, the device <NUM> may be used to stimulate nerves in the palpebral conjunctiva, namely the meibomian glands, or along with adjusting the stimulation waveforms, both the meibomian glands in the palpebral conjunctiva and the afferent nerves governing reflex tearing in the bulbar conjunctiva and sclera. Although the device is shown as having a partially curved outer profile, it will be understood that the device <NUM> may include other shapes, footprints, or profiles than what is shown. For example, the device <NUM> may include a rectangular profile, a circular profile, and elliptical profile, a triangular profile, a bean-shaped profile, or any other suitable profile. Similarly, the electrodes <NUM>, <NUM> may include profiles other than what is shown, and may or may not correspond to or match the overall profile of the device <NUM>. For example, the electrodes <NUM>, <NUM> may include circular profiles, elliptical profiles, rectangular profiles, triangular profiles, bean-shaped profiles, or any other suitable profile.

<FIG> is a flow diagram illustrating a method <NUM> for stimulating nerves using a nerve stimulation device. In this regard, the method <NUM> may be performed using any of the devices <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> described herein. In particular, the method <NUM> may be performed using a nerve stimulation device that includes an antenna configured to receive electromagnetic energy, one or more electrodes configured to create an electrical current in the patient's tissue, and electronic circuitry configured to convert the electrical energy received by the antenna into electrical power to be used by the one or more electrodes. Further, the method <NUM> may be performed using a wireless remote control device, such as the remote control device <NUM> shown in <FIG>.

At block <NUM>, a nerve stimulation device receives electromagnetic (EM) energy with a loop antenna defining an antenna region. The EM energy may be provided by a remote control device, which emits a varying EM field according to a predefined protocol or waveform. As the varying EM field passes through the antenna region, the varying EM field induces a current in the antenna, which is provided to the electronics of the device.

At block <NUM>, the device, specifically the electronic circuitry of the device, generates an electrical pulse pattern based on the received EM energy. In this regard, the electrical pulse pattern may correspond to the predefined protocol or waveform emitted by the remote control device. The electrical pulse pattern may include a variety of characteristics, such as a pulse, a pulse intensity, a pulse frequency, electrode polarity, or any other suitable characteristic. In some aspects, the electrical pulse pattern may be created using a rectifier of the electronic circuitry to convert AC electrical current provided by the antenna into DC electrical current.

At block <NUM>, the device activates a first electrode and a second electrode based on the electrical pulse pattern the first electrode and second electrode overlap with the antenna region defined by the antenna. The first electrode and second electrode comprise electrode surfaces and a plurality of slots within the respective electrode surfaces. The slots extending with in the electrode surfaces may promote near-filed coupling between the antenna of the nerve stimulation device and the remote control device. For example, the slots, which separate the electrodes into a plurality of electrode prongs or fingers, may limit or inhibit the creation of lossy electrical eddy currents which can compromise efficiency and power transfer. Accordingly, by including the slots in the electrodes, the size or footprint of the electrode surfaces can be increased to substantially or entirely overlap with the antenna region, with less interference with the antenna's harnessing of the EM energy.

In some aspects, the wireless remote control device may be configured with smart stimulation features. For example, in the method <NUM>, the wireless remote control device may include a smart phone, or may provide for wireless connectivity with the smart phone (e.g., Bluetooth) using a smartphone app. The remote control device may include a variety of stimulation waveforms for magnetic pulsing and algorithms. A handheld wand may include various treatment tracking features, such as an accelerometer to track the remote control device's treatment motion, and/or a wireless connection with a cellphone to give better treatment advice (figure out where "blindspots" are in treatment). The wireless remote control device may track treatment time(s) and duration, and send reminders.

<FIG> is a top plan view of a therapeutic device <NUM> configured to be worn in a patient's fornix. Similar to the devices described above, the device <NUM> includes a first electrode <NUM> and a second electrode <NUM> disposed on or mounted to a substrate <NUM>. Each electrode <NUM>, <NUM> includes a plurality of electrode prongs or branches <NUM>, <NUM> separated from each other by a plurality of slots. The electrode prongs <NUM>, <NUM> extend inward in opposing directions toward electronic components <NUM> mounted in a central region of the substrate <NUM>. The device <NUM> further includes an antenna trace <NUM> disposed on the substrate <NUM>. The antenna trace <NUM> and the electronic components <NUM> are disposed on a palpebral conjunctiva side, or posterior side, of the substrate <NUM>, while the electrodes <NUM>, <NUM> are disposed on a bulbar conjunctiva side, or interior side, of the substrate <NUM>. The device <NUM> has a bean shape or kidney shape. The shape of the device <NUM> may be selected accounting for curvature of the device <NUM> in at least one axis while being worn by a patient. Further, the electrodes <NUM>, <NUM> are curved upward at the outer regions of the electrodes <NUM>, <NUM>. In some aspects, the wider dimension of the device <NUM>, the spaced configuration of the electrodes <NUM>, <NUM>, and the curvature of the electrodes <NUM>, <NUM> may improve the current density distribution between electrodes to recruit more nerves at a uniform current density. Because the wider dimensions also allow for improved current density distribution vs. volume of tissue, increased neuronal recruitment, and greater curvature of the device <NUM>, the illustrated configuration also penetrates the eye tissue further due to the curved structure of the electrodes <NUM>, <NUM> around the eye. Furthermore, the upward curvature of the electrodes may provide for stimulation of nerves closer to the limbus, where there is higher nerve density, which allows for more efficient stimulation.

The device <NUM> includes a first electrical via <NUM> on the first electrode <NUM>, and a second electrical via <NUM> and third electrical via <NUM> on the second electrode <NUM>. The electrical vias <NUM>, <NUM>, <NUM> may include an aperture or opening in in the electrodes <NUM>, <NUM>, and through the substrate <NUM> to the electronic components <NUM> on the other side of the substrate <NUM>. The vias <NUM>, <NUM>,<NUM> may include a metallic layer or coating (e.g., gold, copper, platinum, iridium, etc.) extending through the aperture or opening, which is connected to an electrical trace leading to a corresponding component of the electronic components <NUM>. The vias <NUM>, <NUM>, <NUM> include conductive ring areas that are wider than the prongs <NUM>, <NUM>. The vias <NUM>, <NUM>, <NUM> are positioned within the pronged or branched electrodes <NUM>, <NUM>, such that the vias <NUM>, <NUM>, <NUM> interrupt the pattern of parallel or co-extending electrode prongs <NUM>, <NUM>. In this regard, the electrodes <NUM>, <NUM>, include a break in at least one prong <NUM>, <NUM> such that each via <NUM>, <NUM>, <NUM> is directly connected to a single prong <NUM>, <NUM> on an outer side of each via, and two or more prongs <NUM>, <NUM> on an inner side of each via (i.e., closer to the electronic components <NUM>). The interrupted configuration of the prongs <NUM>, <NUM> and vias <NUM>, <NUM>, <NUM> shown in <FIG> may promote or facilitate near-field coupling between the antenna trace <NUM> and a remote control device by inhibiting the formation of electrical eddy currents in the conductive layer that includes the electrodes <NUM>, <NUM> and the vias <NUM>, <NUM>, <NUM>. The location of the vias <NUM>, <NUM>, <NUM> within the electrodes <NUM>, <NUM> may allow for sufficient space from the electronic components <NUM>, which may be advantageous for manufacturing purposes.

<FIG> are diagrammatic views of electrical pulse waveforms <NUM>, <NUM> for use in treating ophthalmic conditions, such as DED. In this regard, the electrodes of a nerve stimulation device can be pulsed (e.g., using wireless remote control device <NUM>, <FIG>) according to a predefined pattern or waveform to stimulate nerves in and around the patient's eye to induce tear production. Referring to <FIG>, a nerve stimulation device may be configured to provide a biphasic pulse having a first phase with a positive current I<NUM>, and a second phase with a negative current I<NUM>. The waveform <NUM> may be described or defined by a pulse width tpulse, an inter-pulse width tinterpulse, and a pulse period tPulsePeriod, which is the period of time between pulses of the same phase. In some aspects, the pulse period tPulsePeriod is inversely related to the frequency of the pulse waveform (e.g., inter-pulse frequency = <NUM>/tPulsePeriod). In some embodiments, I<NUM> may range between <NUM> to <NUM> mA, and I<NUM> may range between <NUM> to -<NUM> mA. The current values depend on a variety of other variables, including but not limited to electrode area, tpulse, electrode material, etc.. Further, the tpulse may range from approximately <NUM> to <NUM>. In one example, tpulse is <NUM>. In some embodiments, tinterpulse may range from about <NUM> to <NUM>. In one example, tinterpulse is <NUM>. It will be understood that these values are merely exemplary and that other values for I<NUM>, I<NUM>, tPulsePeriod, tpulse, and/or tinterpulse may be used within the scope of the present disclosure.

The waveform <NUM> shown in <FIG> may be repeated for a number of pulses, and for a period of time. During the period of time, the pulse period tPulsePeriod may vary. For example, the pulse period tPulsePeriod may increase or decrease from pulse to pulse, or a same tPulsePeriod may be used for multiple pulses before changing incrementally over the period of time. In the waveform <NUM> shown in <FIG>, for example, the pulse period tPulsePeriod changes such that the frequency of the pulses, which is based on the inverse of the pulse period (<NUM>/tPulsePeriod), increases and decreases in a linear fashion between F<NUM> and F<NUM>.

The frequencies that are effective for simulating the nerves and inducing tear production may vary from patient to patient. Determining the most effective pulse frequency (tPulsePeriod) for each individual patient may be impractical in some aspects. Accordingly, the waveforms <NUM>, <NUM> shown in <FIG> provide a widely-applicable pulsing pattern, which sweeps through a plurality of pulse frequencies between F<NUM> and F<NUM> in a cyclical fashion. The range of frequencies from F<NUM> to F<NUM> may include nerve pulsing frequencies that are at least partially effective for a large portion of the public, a majority of the public, or even the entirety of the public. The waveform <NUM> may be performed over a time window, in which each frequency between F<NUM> and F<NUM> is pulsed at least two times, at least three times, or more times. In other aspects, the waveform may pulse each frequency between F<NUM> and F<NUM> a single time.

In one example, F1 may be about <NUM> and F2 may be about <NUM>. Accordingly, referring to the waveform shown in <FIG>, the electrodes may be pulsed at <NUM> initially, and then increase linearly from <NUM> to <NUM>, decrease linearly to <NUM>, and then increase linearly again to <NUM>. In some aspects, the entire time window used for the pulsing waveform <NUM> shown in <FIG> may be about <NUM>. However, it will be understood that these values are merely exemplary, and that any suitable values may be used for F<NUM> and F<NUM>, including frequencies larger or smaller than those explicitly mentioned. Further, in other embodiments, the nerve stimulation device may be configured to increase and/or decrease the pulse frequencies non-linearly.

The various parameters of the waveforms <NUM>, <NUM> described with respect to <FIG> may be determined or controlled by a wireless remote control device or transmitter, in some embodiments. For example, referring to <FIG>, the remote control device <NUM> may include a voltage source (e.g., a battery) and an inductor circuit comprising one or more resistors and/or capacitors and a loop inductor, a processor, and a memory component having program code or instructions stored thereon. In some aspects, the remote control device <NUM> may include a power source, which may include a battery, and the power source may be configured to output a variable voltage and/or current (e.g., a sine wave). The processor may be configured to execute the instructions stored on the memory, which may include or define the waveform parameters discussed herein. For example, in some embodiments, the processor may be configured to control the variable power source. The remote control device <NUM> may control the wearable nerve stimulation device <NUM> by transmitting pulsed EM energy corresponding to the waveforms <NUM>, <NUM> shown in <FIG>. In other embodiments, the electronic components of the nerve stimulation device may determine one or more characteristics of the waveforms <NUM>, <NUM>.

The devices and systems described herein can be safely used at home and provide invisible therapy options in a background, or on-demand (acute treatment) method. This system may also gather eye position and blink rate data for other data-driven diagnostics. Localized, protected heating through an underlid device does not require invasiveness or anesthetic to be applied as in other prior art systems, and allows for home-based application. Two different secondary hardware devices (frames or handheld external device) allow for two distinct therapy strategies to be applied with the same underlid device: background, continuously applied therapy, or on-demand, manual therapy (acute treatment).

The nerve stimulation devices, systems, and methods described herein may utilize one or more of the components, devices, systems, or methods described in <CIT>, and <CIT>.

Claim 1:
A device configured to be located underneath an eyelid and worn by a user for treating dry eye, the device comprising:
a flexible substrate;
an antenna disposed on a first side of the substrate and configured to receive electromagnetic energy from a transmitter;
one or more electronic components disposed on the first side of the substrate; and
a first electrode and a second electrode, the first and second electrodes disposed on a second side of the substrate opposite the first side,
wherein the one or more electronic components are in communication with the antenna, the first electrode, and the first electrode, and wherein the one or more electronic components are configured to provide electrical power to the first electrode and the second electrode;
characterized in that each of the first electrode and the second electrode comprises an electrode surface and a plurality of slots in the electrode surface defining a plurality of electrode prongs, wherein the plurality of slots facilitate near-field coupling between the transmitter and the antenna.