Under-eyelid therapeutic appliances and related systems, devices, and methods for treating dry eye

Abstract

According to some embodiments, a device is provided herein for treatment of dry eye, the device being configured to be placed under an eyelid and worn by a user. The device includes a first surface configured to face a portion of the sclera of the eye and a second surface configured to face the eyelid and be completely covered by the eyelid. In some embodiments, the device further includes a plurality of stimulation electrodes proximate the first surface, the plurality of stimulation electrodes configured to stimulate the sclera. The device further includes an energy storage element coupled to the plurality of stimulation electrodes. The energy storage element is configured to provide power to the plurality of stimulation electrodes. The device further includes a processor configured to control the supply of energy from the energy storage element to the plurality of stimulation electrodes to stimulate the sclera.

Description

[Technical field]

[0001] The present disclosure relates generally to ophthalmic systems and devices and related methods for treating dry eye, and in particular to systems and devices and related methods for placement under the eyelid and outside the visual field to stimulate the scleral surface and / or eyelid to induce a blink reflex or reflex tear production to treat dry eye, and / or systems and devices and related methods for heating or otherwise stimulating or exciting the meibomian gland to stimulate meibum production. [Background technology]

[0002] Dry eye is a disease that affects millions of people worldwide. According to a survey, dry eye symptoms are the third most common reason for patients to visit an ophthalmologist for dry eye symptoms. Recently, it has been found that up to 80% of dry eye cases are due to meibomian gland dysfunction (MGD). MGD is caused by the absence or extremely reduced production of lipids in the tear film.

[0003] Normally, the lipid layer produced by the Meibomian glands spreads evenly over the air-tear interface on the cornea as a thin protective film (nanometers thick). Every time a person blinks, a tiny amount of the lipid protective film spreads. However, there are many conditions that can cause this oily layer to not spread evenly over the tear film, and this process can be interrupted, reduced, or even stopped altogether. These underlying causes can include, but are not limited to, age-related changes in hormone secretion characteristics, long-term infections such as skin mites living on the eyelashes or fungal infections that are difficult to remove, general inflammation (blepharitis), autoimmune diseases and allergic reactions, and more recently inadequate blinking due to prolonged exposure to screens, a condition called computer vision syndrome. Without the outer protective lipid layer, the tear film covering the eye has less time to evaporate, leading to the interconnected problems of insufficient tear and meibomian secretion.

[0004] Traditionally, mild MGD has been treated with warm compresses, eyelid cleansers, and gentle eyelid massage, but these approaches prove clinically ineffective in many cases of severe dry eye.

[0005] Recently, a better in-office eye treatment called LipiFlow® has shown clinical promise. This treatment works by heating the meibomian glands in the eyelids and dissolving the clogged oil. The eyelids are heated from the inside, which delivers heat directly to the meibomian glands. In addition, the use of air-filled vesicles and simultaneous pulsatile mechanical pressure can mechanically loosen the clogged glands. However, LipiFlow® and other office-based treatments remain highly invasive and expensive procedures that require a specialized eye doctor. Furthermore, it is estimated that the treatment will need to be repeated several times a year, and the eyes may require local anesthesia.

[0006] Other known eye treatments include applying heat to the outside of the eyelid using a heating pad. In this type of procedure, eye doctors still typically use forceps with moderate pressure to get the glands to work effectively. Furthermore, such treatments remain expensive, as an office visit is generally required to see a medical professional.

[0007] Treatment for aqueous deficient dry eye syndrome (ADDE) includes the application of various artificial tears and the use of pharmaceutical drugs. Recently, a transnasal electrical stimulation device called "TrueTear" has been released, which is effective in treating dry eye. The prior art documents relevant to the invention of this application are as follows (including documents cited during the international phase after the international filing date and documents cited when the application entered the national phase in other countries). (Prior art document) (Patent Documents) (Patent Document 1) U.S. Patent No. 8,831,747 (Patent Document 2) U.S. Patent Application Publication No. 2018 / 0154161 (Patent Document 3) U.S. Patent Application Publication No. 2009 / 0099626 (Patent Document 4) U.S. Patent Application Publication No. 2017 / 0049619 (Patent Document 5) U.S. Patent Application Publication No. 2017 / 0087009 (Patent Document 6) U.S. Patent Application Publication No. 2015 / 0057701 (Patent Document 7) U.S. Patent Application Publication No. 2016 / 0339239 (Patent Document 8) International Publication No. 02 / 18008 Summary of the Invention [Means for solving the problem]

[0008] The present disclosure advantageously describes devices, systems, and methods for treating dry eye. The present disclosure presents novel electrical therapy modalities and devices to the existing portfolio of dry eye treatments. The novel treatment devices and systems described herein provide a socially acceptable user experience, hands-free / scheduled treatment options, and sensor / actuator capabilities to further optimize and improve dry eye disease management.

[0009] According to some aspects, a device is presented that is configured to be placed under an eyelid and worn by a user to treat dry eye. The device comprises a first surface configured to face a portion of the sclera of the eye and a second surface configured to face the eyelid and be completely covered by the eyelid. In some embodiments, the device further comprises a plurality of stimulating electrodes proximate the first surface, the plurality of stimulating electrodes configured to stimulate the sclera. The device further comprises an energy storage element coupled to the plurality of stimulating electrodes and a processor configured to control the supply of energy from the energy storage element to the plurality of stimulating electrodes to stimulate the sclera.

[0010] In some embodiments, the present disclosure describes a system for treating dry eye. The system includes an under-eyelid device configured to be placed between a surface of an eyelid and a surface of an eyeball. The under-eyelid device includes a first surface configured to face the surface of the eyeball and a second surface configured to face the eyelid. The under-eyelid device further includes a plurality of stimulating electrodes closer to the first surface than the second surface, and the plurality of stimulating electrodes are configured to stimulate the surface of the eyeball. The system further includes an external device configured to provide power to the under-eyelid device.

[0011] In some aspects, the present disclosure describes a method of operating an under-eyelid device for treating an ophthalmic condition. In the method, the under-eyelid device includes a plurality of stimulation electrodes configured to stimulate the eye. The method includes placing the under-eyelid device within the lower eyelid and providing power to one or more of the plurality of stimulation electrodes. In some aspects, the under-eyelid device is configured to remain completely under the eyelid during operation and while worn by a user.

[0012] Additional aspects, features, and advantages of the present disclosure are set forth in the detailed description below. [Brief description of the drawings]

[0013] Exemplary embodiments of the present disclosure will now be described with reference to the accompanying drawings, in which: [Figure 1A] 1A and 1B present different views of a portion of one or more typical human eyelids, according to some embodiments of the present disclosure. [Figure 1B] 1A and 1B present different views of a portion of one or more typical human eyelids, according to some embodiments of the present disclosure. [Diagram 2] FIG. 2 shows an overview of the device as it resides under the eyelid according to one positioning and embodiment of the device, in accordance with some aspects of the present disclosure. [Figure 3A]3A-3C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 3B] 3A-3C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 3C] 3A-3C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 4] FIG. 4 is a cross-sectional side view of a device positioned between the lower eyelid and the eyeball, according to some embodiments of the present disclosure. [Figure 5A] 5A and 5B show different views of an exemplary under-eyelid, according to some embodiments of the present disclosure. [Figure 5B] 5A and 5B show different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 6] FIG. 6 is a cross-sectional side view of a device positioned between the lower eyelid and the eyeball, according to some embodiments of the present disclosure. [Figure 7] FIG. 7 is a cross-sectional side view of a device according to some embodiments of the present disclosure. [Figure 8] FIG. 8 is a cross-sectional side view of a device positioned between the lower eyelid and the eyeball, according to some embodiments of the present disclosure. [Figure 9] FIG. 9 shows an overview of the under-lid device when present under the eyelid along with an external device according to one positioning and embodiment of the device in accordance with some aspects of the present disclosure. [Figure 10] FIG. 10 shows an overview of the under-lid device when present under the eyelid along with an external device according to one positioning and embodiment of the device in accordance with some aspects of the present disclosure. [Figure 11A] FIG. 11A shows an example of an under-lid device system in use, according to some embodiments of the present disclosure. [Figure 11B] FIG. 11B illustrates an example of an under-lid device system in use, according to some embodiments of the present disclosure. [Figure 12]FIG. 12 shows a diagram of an exemplary under-eyelid device according to some aspects of the present disclosure. [Figure 13A] 13A-13C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 13B] 13A-13C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 13C] 13A-13C provide different views of an exemplary under-eyelid device according to some embodiments of the present disclosure. [Figure 14] FIG. 14 is a cross-sectional view of a heat reflective and insulating layer according to some embodiments of the present disclosure. [Figure 15A] 15A-15C show different views of a rod according to some embodiments of the present disclosure. [Figure 15B] 15A-15C show different views of a rod according to some embodiments of the present disclosure. [Figure 15C] 15A-15C show different views of a rod according to some embodiments of the present disclosure. [Figure 16] FIG. 16 illustrates and presents an exemplary under-eyelid device system in use, according to some embodiments of the present disclosure. [Figure 17A] 17A and 17B show examples of an under-lid device system in use, according to some embodiments of the present disclosure. [Figure 17B] 17A and 17B show examples of an under-lid device system in use, according to some embodiments of the present disclosure. [Figure 18] FIG. 18 illustrates the principle of how an under-eyelid device system operates, according to some embodiments of the present disclosure. [Figure 19] FIG. 19 shows example stimulation waveforms according to some aspects of the disclosure. [Figure 20] FIG. 20 is an exemplary method of operating an under-eyelid device system according to some aspects of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] For the purpose of facilitating the understanding of the principles of the present disclosure, reference will now be made to the embodiments shown in the drawings and specific language will be used to describe them. Nevertheless, it will be understood that no limitations on the scope of the present disclosure are intended. Any changes and further modifications to the described devices, systems, and methods, and any further applications of the principles of the present disclosure, as would normally occur to one skilled in the art to which the present disclosure pertains, are fully contemplated and included in the present disclosure. In particular, it is fully contemplated that the features, components, and / or steps described with respect to one embodiment can be combined with the features, components, and / or steps described with respect to other embodiments of the present disclosure. However, for the sake of brevity, multiple iterations of these combinations are not described individually herein.

[0015] 1A and 1B are different views of one or more portions of a typical human eyelid. FIG. 1A shows a cross-sectional side view of the upper eyelid. The upper eyelid has multiple meibomian glands (numbered 110), one of which is shown in FIG. 1A and multiple meibomian glands are shown in FIG. 1B.

[0016] Disclosed herein is a device for placement under the eyelid. The device includes one surface facing the eyelid and another surface facing the sclera. In some embodiments, the device includes an electrode configured to stimulate the sclera to induce a blink reflex and / or generate reflex tears. Also, in some embodiments, the under-eyelid device includes a heating element on the eyelid side to heat the meibomian glands of the eyelid to unclog the glands and / or stimulate the meibum. In some embodiments, the under-eyelid device further includes a magnetic body that responds to an external magnet that engages the under-eyelid device to enhance eyelid massage and / or eyelid heating. The under-eyelid device may include a combination of the aforementioned features.

[0017] FIG. 2 illustrates an example of an under-eyelid device 200. Each of the devices 200 is positioned under the eyelid, and FIG. 2 illustrates the profile of each device 200 as it would reside under each eyelid according to one positioning and embodiment of the device 200. The device 200 is designed to be worn by a user and to be fully covered by the eyelid and reside under the eyelid, even when the eyelid is open as shown. In this embodiment, each device 200 has a generally rectangular shape, although each device is not limited to this shape. The device 200 is configured to treat dry eye by applying heat to the Meybomian glands and / or applying stimulation to the sclera and / or conjunctival surfaces, as further described herein. As is well known, the sclera generally refers to the thick white layer that constitutes the white part of the eye, while the conjunctiva generally refers to the thin layer that surrounds the entire eye except for the cornea. Additionally, stimulation of the sclera or conjunctival surfaces can induce blinking and reflex tearing, both of which are useful in treating dry eye. It is generally understood that any discussion of irritation to the sclera or scleral surfaces includes irritation to the conjunctival surface overlying the sclera.

[0018] The form factor of each device 200 is favorable because it substantially covers a relatively small amount of the ocular surface compared to contact lenses. Furthermore, contact lenses can exacerbate dry eye by interfering with the interaction between tears, the oil components produced by the meibomian glands, and the eye itself. Device 200 is free of such drawbacks. Moreover, advantageously, device 200 does not adversely affect the user's vision because device 200 is not in the user's field of vision.

[0019] 3A-3C present different views of an exemplary under-eyelid device 300, which is an exemplary embodiment of device 200. FIG 3A presents a view of the surface of device 300 for facing the sclera, FIG 3B presents a view of the facing surface of device 300 for facing the eyelid, and FIG 3C presents a cross-sectional side view of device 300. In general, the components shown in the view of device 300 in FIG 3A are used to stimulate the surface of the eye to stimulate blinking and reflex tearing.

[0020] Beginning with FIG. 3A, the scleral side of the device 310 includes multiple stimulating electrodes 380. The embodiment of FIG. 3B includes 16 stimulating electrodes 380, as an illustrative and non-limiting example. However, in general, the device 310 has two or more stimulating electrodes, or four or more stimulating electrodes. The electrodes 380 provide neural stimulation of cold or nociceptors on the scleral surface to produce reflex tearing. The stimulation waveform is designed to produce reflex tearing while remaining below the pain threshold. The device 310 may be covered by a material 385, such as a silicone elastomer or silicone hydrogel or hydrogel, that is comfortable for the user when the device 310 is placed under the eyelid and against the eyeball. By using multiple electrodes, different electrodes or pairs or sets of electrodes can be activated at different times to apply patterned stimulation that stimulates the sclera in different areas and directions. The greater the number of electrodes, the greater the potential for variation in stimulation patterns. In some embodiments, a blink rate is generated by applying a periodic stimulation waveform to the electrodes.

[0021] As shown, the device 300 may also include an antenna 350. The illustrated antenna 350 is configured as a loop antenna, but in general, the antenna 350 may take any useful form for performing wireless charging via inductive wireless charging and / or for providing communication capabilities to the device 310. The antenna 350 may be present on the surface of the device 310 or may be present inside the device 310. The antenna 350 here is also referred to as a wireless charging device. Wireless inductive charging is achieved by coupling the antenna 350 to an external device that provides energy to the device. The antenna 350 is coupled to the energy storage element 330 such that the antenna provides the power received by the antenna to the energy storage element 330 to charge the energy storage element 330.

[0022] Turning to FIG. 3B, device 300 may also include an integrated circuit (IC) 370 and / or an integrated passive device (IPD) 360. In one embodiment, IC 370 is configured to provide any combination of the following: power management (such as managing energy storage element 330 or providing energy via wireless charging), eyeblink sensing, eyeblink timing, or scleral / conjunctival surface nerve stimulation for tear production and / or stimulation of the blink reflex. Electrodes 380 may be controlled by IC 370 to generate any known type of nerve stimulation waveform, such as waveforms utilizing any effective combination of pulse width, pulse frequency, pulse amplitude, function duration, on time, and / or off time. Antenna 350 is located on or within device 310.

[0023] The device 300 further includes an energy storage element 330 that stores energy for powering the device 300. Examples of the storage element 330 include a battery and a capacitor. The device 300 further includes two electrodes 340. The electrodes 340 may be configured to detect the onset of a blink, for example, via electromyogram (EMG) or ambient environmental impedance sensing, to provide blink detection. For example, the electrodes may measure an electrical potential or voltage generated by the conjunctiva or other cells of the eyeblink to detect the onset of a blink. The electrodes 340 may also be configured to stimulate an eyelid muscle to induce a person to blink, or may alternatively be configured to induce an eyeblink. For example, in some embodiments, the IC 370 is coupled to the electrodes 340 to provide both blink detection and blink stimulation, taking one or more measurements from the electrodes 340 to perform blink sensing and adapting a voltage or current to the electrodes to stimulate the eyelid to perform blink stimulation.

[0024] In some embodiments, the device width of 316 is about 4 millimeters (mm) and the device length of 318 is about 12 mm. In some embodiments, the energy storage element 330 is a 7.5 mF supercapacitor having dimensions of about 3.2 mm x 2.5 mm x 0.9 mm, the integrated circuit 370 has dimensions of about 1.2 mm x 1.2 mm x 0.08 mm, and the IPD 360 has dimensions of about 1.0 mm x 1.0 mm x 0.08 mm. These dimensions are exemplary and not intended to be limiting.

[0025] Thus, device 310 can be used to treat dry eye using electrode 340 to provide blink stimulation and / or to treat dry eye using electrode 380 to generate reflex tears or to stimulate the surface of the eye to stimulate blinking.

[0026] Any pair of electrodes, such as electrode 340, can be used to measure tear osmolarity based on impedance measurements, such as using impedance spectroscopy. For example, impedance measurements can be performed (at DC) using a potentiostat circuit, or a frequency-adjustable sine wave from one electrode can be swept across frequencies and analyzed via phase and magnitude on the return from the other electrode. By measuring the impedance of the tear to determine osmolarity, device 300 can perform closed-loop treatment of dry eye. For example, if the impedance measurement indicates that the eye requires treatment, device 300 can apply heat and / or stimulation as described earlier herein. Measurements from the electrodes are provided to a processor, such as integrated circuit 370, which determines whether heating and / or stimulation should be applied based on the measurements. For example, if the measurements indicate that tear osmolarity exceeds a threshold, heating and / or electrode stimulation can be applied.

[0027] 3C, there is shown a cross-sectional side view of device 300. Energy storage element 330, electrode 380, and covering material 385 are shown.

[0028] 4 is a cross-sectional view from the underside of device 300 positioned between the lower eyelid 420 and the sclera of eyeball 430. In other words, FIG. 4 is a cross-sectional perspective view of device 300, lower eyelid 420, and eyeball 430 from the underside of device 300 when positioned between lower eyelid 420 and eyeball 430. Consistent with the above description, electrode 380 is positioned on the side facing sclera 430.

[0029] 5A and 5B show different views of an exemplary under-eyelid device 500 according to some aspects of the present disclosure. Features of the device 500 that are the same as those previously described utilize the same numbering and generally will not be described further. The view of the device 500 in FIG. 5A is from an eyelid perspective. In other words, FIG. 5A presents the eyelid-facing portion of the device 500. The device 500 includes a number of heating elements 520, examples of which are resistors or resistive heating elements. FIG. 5A presents an embodiment having 24 heating elements 520 for illustrative purposes, but generally any number of heating elements may be included in the under-eyelid device 500. In some embodiments, the heating elements 520 are 100Ω resistors.

[0030] Turning to FIG. 5B, a cross-sectional side view of the device 500 is shown. The energy storage element 330, the heating element 520, and the covering material 385 are shown. Additionally, a heat reflector 590, such as a Mylar heat reflector, is illustrated. The heat reflector 590 is designed so that heat generated from the resistive heating element 520 does not harm any portion of the human eye located on the opposite side of the device. The heat reflector 590 may form a layer within the device 500 located between the heating element 520 and a surface 595 configured to face the sclera of the eye. The heating element 520 is positioned proximate to a second surface 596 of the device 500 configured to face the eyelid. The heating element is positioned proximate to the second surface 596 to facilitate heating of the eyelid. When power is provided to the heating element 520, the temperature of the heating element 520 increases. The heating element 520 facilitates heat transfer to the eyelid tissue facing the heating element 520. In some embodiments, power is supplied to the heating element 520 from the energy storage element 330.

[0031] 6 is a cross-sectional view from the underside of device 500 positioned between lower eyelid 420 and the sclera of eyeball 430. In other words, FIG. 6 is a cross-sectional perspective view of device 500, lower eyelid 420, and eyeball 430 from the underside of device 500 when positioned between lower eyelid 420 and the sclera of eyeball 430. Consistent with the above description, heating element 520 is positioned on the side facing lower eyelid 420.

[0032] In some embodiments, the under-lid device includes a heating element but does not include electrodes, such as device 500 illustrated in Figures 5A, 5B, and 6. In some embodiments, the under-lid device includes electrodes but does not include a heating element, such as device 300 illustrated in Figures 3A-3C and 4. Depending on the desired application, the under-lid device can be configured to provide only heating of the meibomian glands using a heating element or only stimulation of the ocular surface using electrodes. In some embodiments, the under-lid device can include both electrodes and a heating element. Such a device is shown in Figure 7.

[0033] 7 is a cross-sectional side view of a device 700 according to some embodiments of the present disclosure. Features of device 500 that are the same as those previously described utilize the same numbering and generally will not be further described. Device 700 includes an electrode 380, a heating element 520, and a heat reflector 590, such as a Mylar heat reflector. The device includes a first surface configured to face the eyeball and a second surface configured to face the eyelid. A cross-section of the first surface is shown in FIG. 7 as 795, and a cross-section of the second surface is shown as 796.

[0034] 8 is a cross-sectional view from the underside of the device 700 positioned between the lower eyelid 420 and the sclera of the eye 430. In other words, FIG. 7 is a cross-sectional perspective view of the device 700, the lower eyelid 420, and the sclera 430 from the underside of the device 700 when positioned between the lower eyelid 420 and the sclera 430. Consistent with the above description, the heating element 520 is positioned on the side of the device 700 facing the lower eyelid 420, and the electrodes are positioned on the side of the device 700 facing the sclera 430.

[0035] There are a variety of potential uses for under-eyelid devices as described herein. In one use case, device 200 is used in conjunction with a glasses form factor 910, as shown in FIG. 9. As shown in FIG. 9, an under-eyelid device 200, such as device 300, 500, or 700 previously described, is placed under each eyelid of a person as shown. An outline of under-eyelid device 200 placed under the person's eyelid is shown. Device 200, such as device 300, 500, or 700, is designed to be worn by a user and remain fully covered by and under the eyelid, even when the eyelid is open as shown.

[0036] The person also wears an associated eyeglass frame 910. The frame 910 may include a portion that rests over the person's ear (not shown), and the frame 910 may or may not include a glass eyepiece. The frame 910 may be in the shape of any type of known eyeglass frame. Thus, FIG. 5 illustrates a system for stimulating a human eye, including one or more devices 200 and a frame 910.

[0037] However, the frame 910 may include electronics for operating the device 200. For example, the frame 910 may include a power transfer and communication coil, such as an antenna, for wirelessly coupling to a coil or antenna, such as the antenna 350 described above. Eyeblink detection may be performed by the frame 910 via an inward-facing infrared reflectometer or camera and communicated to the under-eyelid device, or may use EMG or environmental impedance sensing electrodes on the under-eyelid device 200 itself. Since energy for stimulation and / or heating may be provided by the frame 910, the under-eyelid device 200 may or may not include an energy storage element. If the under-eyelid device 200 includes an energy storage element, the frame 910 may charge the energy storage element and / or provide energy to the under-eyelid device as needed.

[0038] Each device 200 can perform eye blink detection and energy harvesting monitoring. If there is sufficient power harvesting and a blink is detected, the device 200 can activate heating via a resistive heating element such that the heating occurs in synchrony with the blinking of the eyelid. One reason for synchronizing heating with blinking is that there is limited power available for heating, so the application of heat can melt the wax / oily lipid layer and "unclog" the meibomian glands. The blinking action naturally acts to expel meibomian oil from the meibomian glands.

[0039] Instead of detecting blinks, other embodiments utilize electrodes on the eyelid side to stimulate the eyelid muscles prior to application of heat to suggest, stimulate, or induce blinking during heating. In some embodiments, an on-chip timer in device 200 is utilized to ensure that this does not happen too frequently or too slowly (using the same electrodes to sense the average blink rate over a long period of time when there is not yet enough harvested power to perform a stimulation event). Additionally or alternatively, stimulation may be applied periodically via stimulation electrodes on the sclera side to induce natural tear production.

[0040] A second use case for device 200 is shown in Figure 10. This use case includes a system including one or more devices 200, such as devices 300, 500, or 700 described above, and a hand-held wand 1010. Instead of the wand 1010, the system may use a glove or finger cot. Regardless of whether a wand 1010 or a glove or finger cot is used, each of these may be referred to as an external device, and the external device in some embodiments includes a wireless power transfer coil at the fingertip to provide sufficient power to heat device 200 via a resistive heating element as described herein, and for communication with device 200.

[0041] The buttons on the external device, such as the device 1010, can be easily operated with a thumb to enable / disable heating or to activate scleral stimulation to produce tears. When the user feels that their eyes are dry, they can hold the external device, such as the device 1010, opposite the location where the under-eyelid device 200 is placed and gently massage their eyelids. At the same time, the button on the external device, such as the device 1010, can be held down to allow heating. Because the distance between the power transmission coil of the external device and the under-eyelid device is small, a lot of power can be transmitted to provide continuous heating. The continuous heating occurs all the time the user is massaging the eyelids, helping to mechanically and thermally stimulate the Meibomian glands. If desired, the user can also press the button on the external device 1010 to have the under-eyelid device 200 stimulate the scleral surface to produce tears.

[0042] In yet a third use case, the under-eyelid device 200 has an energy storage element sufficient to power the device 200 for continuous operation over a relatively long period of time (e.g., days or weeks) without requiring an external device to provide power or control for such operation. For example, the energy storage element of the under-eyelid device 200 may be a battery. In such an embodiment that does not require an external device, the under-eyelid device 200 includes a processing device, such as a processor or IC, configured to initialize heating with the heating element or initialize neural stimulation with the electrodes according to a predefined schedule or criteria. The under-eyelid device 200 in this third use case may be removed from under the eyelid, placed in a charging device to charge the energy storage element, and then placed back under the eyelid. In this manner, the under-eyelid device 200 may be used repeatedly over a period of days.

[0043] 11A and 11B present an example of an under-eyelid device system in use, according to one embodiment. The under-eyelid device system includes an under-eyelid device 200 and an external device 1110 (or a device external to the human user). FIG. 11A is a perspective view of the under-eyelid device 200 and the external device 1110, and FIG. 11B is a top view of the external device 1110. FIG. 11A illustrates one potential electromagnetic coupling between the under-eyelid device 200 and the external device 1110. Each device utilizes an antenna 750 that can be used for wireless charging of the under-eyelid device 200 and for communication between the devices 1110 and 1110. As shown, the external device 1110 includes an energy storage element 1130 that is used to power the under-eyelid device 200. The energy storage element may be a battery, such as a rechargeable battery. In this embodiment, the external device 1110 includes electronics 1140 that includes a processing device, such as an IC or processor, for controlling the external device 1110. In some embodiments, the electronics 1140 may also include memory for storing instructions executed by the processing unit.

[0044] FIG. 12 illustrates an under-eyelid device 1200 for blink detection and closed-loop blink stimulation. The device 1200 includes a pair of electrodes 1280, an antenna 1250, and an IC 1270 for wireless power, communication, power management, stimulation, and tear film osmolality estimation via wideband impedance spectroscopy measurements. The device may also include a supercapacitor for energy storage to power the device 1210. The pair of electrodes 1280 are used to estimate tear film osmolality via wideband impedance spectroscopy measurements. The pair of electrodes 1280 are also used to stimulate blinking. The device 1210 is configured to be placed under the upper and lower eyelids of a human patient's eye. The electrodes 1280 may face the surface of the eye or the surface of the eyelid.

[0045] 13A-13C present three perspective views of another embodiment of an under-eyelid device 1300. FIG. 13A presents a view of the front or anterior components of the under-eyelid device 1300 configured to be placed against the eyelid. FIG. 13B presents a view of the back or posterior components of the under-eyelid device 1300 configured to be placed facing the surface of the eye. FIG. 13C presents a cross-sectional side view of the under-eyelid device 1300. Exemplary dimensions are a length 1318 of about 12 mm and a width of about 4 mm, although other dimensions are contemplated by the present disclosure.

[0046] As shown, the device 1300 of FIG. 13A includes an antenna 1350 for wireless charging and / or communication, eight heating elements 1320, four magnetic stacks 1380, an integrated circuit 1350, and a covering material 1390. The number of heating elements 1320 and magnetic stacks 1380 are merely exemplary, and any number of these elements may be used. The integrated circuit 1350 may be used for power rectification, power distribution to the heating elements 1320, and / or temperature sensing for safety (utilizing a temperature probe placed on either the eyelid side of FIG. 13A or the sclera side of FIG. 13B), among other functions. FIG. 13B shows the features of the device 1300 from the eye side. The covering material may be made of SiHy and form a moisture barrier.

[0047] One embodiment of a magnetic stack 1380 is shown in Figure 14. The magnetic stack 1380 includes a thermal heat shield 1375, a magnetic material 1385, and an insulating material 1390, such as aerogel. The thermal heat shield 1375 helps to reduce heat directed at the eyelid from reaching the sclera. Examples of magnetic material 1385 are highly ferromagnetic metals or magnets.

[0048] 13C shows a cross-sectional view of device 1300. Device 1300 optionally includes a groove, such as groove structure 1395 molded into under-lid device 1300 around heating element 1320 to enhance localized pressure and / or aid in heat transfer to the eyelid.

[0049] An under-eyelid device, such as device 1300 illustrated in FIGS. 13A-13C, can have any combination of the following characteristics: The under-eyelid device avoids the use of anesthesia of the ocular surface (other prior art techniques require anesthesia) so that the device can cover the eye. The under-eyelid device may use radio frequency (RF) energy collection methods to convert energy into resistive heating. The lower eyelid device may employ a special magnetically sensitive stack or stack-up (using permanent magnets or ferromagnetic materials) that responds to an external magnetic field such that the eyelid is compressed between an external handheld stimulation device and the lower eyelid device. The stack-up also includes materials to reflect, shield, and insulate heat from resistive heating from reaching the scleral surface. The under-eyelid device may also include groove structures, "dimples," chevrons, or other related features that can increase localized pressure around the feature to aid in excavating the meibomian glands of the meibum when the under-eyelid device is moved or pulsed by the magnetic field and movement of the external manually held stimulation device while the electromagnet within the manually held device is energized. The under-eyelid device may also include safety features such as tracking the temperature of the under-lid for protection.

[0050] A device such as device 1300 presented in Figures 13A-13C can be designed to be used with a wand, which may be sized for handheld use. Figures 15A-15C show different views of an exemplary embodiment of a wand 1500 for use with an under-eyelid device such as device 1300. Wand 1500 may also be referred to as a handheld stimulation device. Dimension 1518 of wand 1500 may be approximately 14 mm, although any width may be used. Dimension 1516 of wand may be approximately 6 mm, although any width may be used.

[0051] The wand 1500 includes a pressure sensor 1510, an antenna 1520, a coil 1530, electronics 1540, an energy storage device 1550 such as a battery or capacitor, and a user interface 1560. The antenna 1520 may be used to receive power provided by induction for wireless charging and / or wireless communication. The pressure sensor 1510 may be used to detect application of the wand 1500 to the skin of a user. The coil 1530 may include a ferrite core to enhance the use of the coil 1530 as an electromagnet. In one embodiment, the electronics 1540 may include an integrated circuit or other type of processor for controlling the supply of power to the device 1500, wireless communication, and / or magnetization of the coil 1530. The user interface 1560 may be utilized by a user to control the positioning or activation of the under-eyelid device. For example, the user interface 1560 may include buttons or an electronic touch display to allow a user to control or activate electronic, thermal, or mechanical stimulation (described below) of the under-eyelid device.

[0052] A wand, such as wand 1500 shown in FIGS. 15A-15C, can have any combination of the following characteristics: the wand can include a wound electromagnet powered by a switchable DC current source; a power delivery antenna powered by an adjustable RF (AC) source; and / or buttons and knobs that allow a user to set the amplitude, pulse, and other parameters that provide therapeutic heating and mechanical stimulation modes as needed or desired. The wand can include safety and / or treatment tracking features by tracking the wand's movement, treatment time, treatment duration, treatment frequency, and / or treatment effect, or alternatively, can track the wand's movement, treatment time, treatment duration, treatment frequency, and / or treatment effect. The wand can include a pressure sensor to track the applied force. Such a pressure sensor can be used to indicate when and for how long treatment has been applied.

[0053] 16 illustrates the use of an under-eyelid device system including an under-eyelid device 200, such as any of the under-eyelid devices described herein. The under-eyelid device system includes a stimulation wand 1500 as shown, and a lower eyelid device 200 positioned under the eyelid. FIG. 16 illustrates a cross-sectional side view of the wand 1500.

[0054] FIG. 16 shows an exemplary embodiment of a waveform used during operation of the wand to provide stimulation and a corresponding exemplary temperature response inside the eyelid during operation. The electromagnetic coil 1530 in the wand 1500 is selectively magnetized to engage the under-eyelid device and assist in the movement of the device. This is illustrated as "Magnetic Repositioning of Under-eyelid Device" in FIG. 16. Energy from the signal propagated by the RF antenna is utilized to power a resistive element, heating the meibomian glands of the eyelid. FIG. 16 shows an example of one such signal from the wand's RF antenna and the resulting temperature of the lower eyelid as the signal is received by the lower eyelid device. The electromagnetic coil 1530 of the wand 1500 is magnetized in a pulsed manner to alternately compress and release the under-eyelid device 200 against the eyelid.

[0055] The wand 1500 may utilize various safety features or systems for safety. Magnetic force may be sensed and limited by pressure sensor 1510. Temperature may be sensed and heating limited using integrated circuits in electronics 1530. Additionally, radio frequency (RF) antenna 1520 and coil 1530 can coexist operating since RF antenna 1520 operates with alternating current (AC) and coil 1530 utilizes direct current (DC).

[0056] FIG. 17A illustrates an example of an under-eyelid device system before repositioning of the under-eyelid device 200, and FIG. 17B illustrates an example of an under-eyelid device system after repositioning of the under-eyelid device 200. Repositioning is accomplished through the use of an electromagnet in the wand 1500 shown. A direct current is applied to a coil in the wand as shown, magnetizing the electromagnet and engaging the under-eyelid device. After repositioning the under-eyelid device using the electromagnet, the electromagnet can be used to stimulate the under-eyelid device, alternately squeezing and relaxing the eyelid, thereby stimulating the eyelid. The pulsed square wave of the waveform in FIG. 17B is one example of a waveform for achieving such eyelid stimulation, although other waveforms may be used.

[0057] Firmly pressing, massaging, or squeezing the lower eyelid as shown in Figure 17B has the following features and advantages. First, the force is concentrated on the expression of the Meibomian gland. Second, no excessive pressure is applied to the eyeball. Third, the frequency and pulse amplitude may be controlled by a wand or other external device. Fourth, the pressure can be measured with a pressure sensor built into the external device such as a wand. Fifth, the squeezing force generated between the ferromagnetic body of the under-eyelid device and the electromagnet of the external device such as a wand depends on the area where the ferromagnetic body is in contact with the eyelid, not on the volume of the ferromagnetic body.

[0058] An example stimulation bar electromagnet design has the following parameters: An electromagnet of approximately 1.4 Tesla provides sufficient squeezing force across a typical eyelid thickness of 3 mm. A soft iron core with a relative permeability of 5K, 36 gauge magnet wire with a resistance of 400 ohms / ft at approximately 100 turns / inch. The design includes a 1 inch long electromagnet with a 1 / 4 inch wide head (providing a resistance of approximately 5 ohms) with a length of approximately 157 inches or 13 feet. With a current of 0.2 A, this design results in a voltage drop of 1 volt and a magnetic field of approximately 2.5 T.

[0059] 18 shows an example of an electromagnet 1830 engaging the magnetic under-eyelid device 200 when the under-eyelid device is placed under the eyelid 1810. Maximum magnetic field coupling and magnetic field gradient creates a lateral force on the under-eyelid device 200, locking its lateral position in place.

[0060] Examples of features and functions of smart stimulation wands include: form factor - whiteboard marker size, outer under-eyelid device contact surface - anti-microbial, connectivity - Bluetooth connection to smartphone app. Handheld wands, such as wand 1500, may include various stimulation waveforms for magnetic pulses and algorithms. Handheld wands may include various treatment tracking features, such as an accelerometer to track the treatment motion of the wand, and / or wireless connectivity with a cell phone to provide better treatment advice (figuring out where the "blind spots" in treatment are and suggesting to the user where they should spend more time), or not staying in one place for enough time. Portable wands may track treatment time and duration and send reminders. Portable wands can utilize a pressure sensor at the tip of the wand to know the force applied (protection and data). Under-eyelid devices used with portable wands can utilize, for example, heat stimulation to dissolve meibomian glands stuck in the meibomian glands. Such under-eyelid products may also additionally or alternatively utilize mechanical stimulation to provide direct current and pulsed magnetic fields to actuate the under-eyelid device.

[0061] An example of the use of the under-eyelid device system is shown below.

[0062] The subpalpebral device is inserted into the upper or lower eyelid (either is acceptable for treating MGD). The wand is placed close to the lower portion of the outer eyelid. Heating is performed by enabling RF on the wand. Circuitry in the under-eyelid device may detect the temperature of the eyelid surface (heated surface) as well as the eyeball surface to ensure operation is within safe limits. An alternating current is passed through the rod to pulse the electromagnet and initiate the pulse / squeeze. The tip of the rod is fitted with a pressure sensor, which prevents excessive pressure from being applied to the eyelids even if too much current is passed through the electromagnet. A rod-shaped electromagnet with a direct current passing through it "grabs" the lower eyelid device, allowing it to clamp the lower eyelid. By sliding the under-eyelid device while the electromagnet is activated, a mechanical "wiping" stimulus can be applied, allowing the under-eyelid device to be moved to a different treatment area. During this treatment time, the wand tracks its movement to track which part of the lower eyelid it is treating, and for how long (and with what thermal and mechanical stimulation) each part of the lower eyelid is treated. Using Bluetooth connectivity and a smartphone app, it gives the user useful feedback and coaching on which areas have been sufficiently treated and which areas need more treatment (wiping, pulsing action, more heat, etc.).

[0063] The smartphone application can send users reminders for follow-up treatment and can also send push notifications to ask questions about the user's dry eye disease and treatment so that treatment is proactive rather than reactive.

[0064] As previously described, the electrodes of the under-lid device may be controlled by an integrated circuit or other processor to generate any known type of neural stimulation waveform, such as a waveform utilizing any effective combination of pulse width, pulse frequency, pulse amplitude, duty cycle, on-time, and / or off-time, etc. Figure 19 shows an example of a neural stimulation waveform in accordance with some aspects of the present disclosure. This waveform may be applied via any of the electrodes of an under-lid device having stimulation electrodes as introduced herein.

[0065] As shown in FIG. 19, the example waveform has a pulse width of 50 μs (microseconds), although pulse widths up to 250 μs can be used in this example. The pulses are applied at a frequency between 20 Hz and 640 Hz. That is, the time from the start to the end of each pulse is approximately 1 / (20 Hz) to 1 / (640 Hz). FIG. 19 shows frequency versus time for an example stimulation pulse. The stimulation signal is a frequency chirp signal whose frequency increases at regular intervals and then decreases at regular intervals. As shown, the frequency increases linearly from 20 Hz to 640 Hz in 0.5 seconds, decreases linearly from 20 Hz to 640 Hz in the next 0.5 seconds, and repeats. This disclosure recognizes that different people have different resonant frequencies of neural receptors, i.e., frequencies of stimulation effective to induce tear production. By sweeping the pulse frequency at a moderate rate, the frequency chirp signal can be used across a population without the need for tuning or calibration to find each person's specific neural resonant frequency. In some embodiments, a processor (such as IC 370) within devices 200, 300, 500, 700, and / or 1300 is configured to control the supply of power from an energy storage element (such as energy storage element 330) to apply chirp stimulation signals to various sets of electrodes within those devices to stimulate the sclera and / or conjunctiva.

[0066] The pulses may be monophasic, but alternatively, biphasic pulses may be used, as shown in Figure 19. A low pulse width can be utilized to facilitate targeting of neurons that promote tear secretion while avoiding simulation of other types of neuroreceptors.

[0067] FIG. 20 illustrates a method 1900 for treating dry eye symptoms using an under-eyelid device, such as any of the under-eyelid devices presented herein, for example, devices 200, 300, 500, 700, or 1300. Method 1900 begins at step 1910. At step 1910, an under-eyelid device, such as an embodiment of a under-eyelid device previously described, is placed under the patient's eyelid. For example, the under-eyelid device is placed between the eyelid and the eyeball, as shown in FIGS. 4, 6, 8, or other figures herein. Once placed, at step 1920, a determination is made as to whether a condition is met. Step 1920 is an optional step that may not be employed. For example, method 1900 may proceed directly from step 1910 to step 1930, where treatment is applied.

[0068] Returning to step 1920, the condition may be detected by a sensor in the under-lid device. According to one embodiment, the sensor may include a pair of electrodes, such as electrodes 340 in FIG. 5A, that are used to measure tear film conductance or impedance, which can be used to provide a measurement of tear osmolarity, as discussed herein. In one embodiment, if the tear osmolarity exceeds a threshold, thereby signaling a dry eye condition, the condition of step 1120 is met and a treatment is applied in step 1930, thereby providing relief or treating the dry eye condition. In some embodiments, the treatment includes providing power to various electrodes, such as electrode 380, to stimulate the sclera to cause reflex blinking or reflex tear production. In some embodiments, the treatment includes providing power to various heating elements, such as heating element 520, to heat meibomian glands in the eyelid to stimulate meibum production and / or unclog the glands to relieve dry eye. In some embodiments, treatment involves both stimulating the sclera and heating the Meibomian glands using an under-eye device such as that illustrated in FIGS.

[0069] In some embodiments, the treatment of step 1930 includes utilizing an external device, such as a hand-held wand. An exemplary wand is illustrated herein as wand 1500. The external device is utilized to engage an under-lid device that includes a magnetic material. Examples of under-lid devices with magnetic material are illustrated in FIGS. 13A-13C. The treatment includes the wand generating magnetic pulses to alternately compress and release the eyelid between the wand and the under-lid device. The magnetic pulses may be periodic or non-periodic. This alternating compression and release action massages the meibomian glands to unclog the glands and / or stimulate meibum production. The treatment also includes powering a heating element of the under-lid device to apply heat to the meibomian glands and powering electrodes to stimulate blinking and reflex tearing. The electrodes may face either the eyelid or the sclera.

[0070] In operation, the under-lid device may utilize electrodes or other sensors to detect blinks. By detecting blinks and tracking the time between blinks, the under-lid device may calculate a blink rate for a given time interval. In an embodiment, the blink rate is calculated as the number of blinks detected in the time interval. The blink rate may be used as a condition in step 1920. For example, if the blink rate is too low, the method 1900 may proceed to step 1930 and provide power to the electrodes to stimulate one or more blinks to increase the blink rate to an acceptable level.

[0071] In step 1940, the under-eyelid device is removed from between the eyelid and the eye. The under-eyelid device may be removed for cleaning, charging the energy storage element, replacement, or disposal, for example.

[0072] The devices and systems described herein can be safely used at home, providing an unseen treatment option in a routine, unobtrusive setting or on-demand (acute treatment) manner. The system can also collect eye position and blink rate data for other data-driven diagnostics. Localized, protected heating via the under-lid device allows for at-home application without the need for invasiveness or application of anesthetic drugs as in other prior art systems. Two different hardware devices (frame or portable external device) allow for the application of two different treatment strategies with the same under-lid device: treatment applied continuously in a routine, unobtrusive setting or treatment by hand on-demand (acute treatment).

[0073] Those skilled in the art will recognize that the above-mentioned devices, systems, and methods can be modified in various ways. Therefore, those skilled in the art will understand that the embodiments covered by the present disclosure are not limited to the specific exemplary embodiments described above. In that regard, although exemplary embodiments have been shown and described, the foregoing disclosure contemplates a wide range of modifications, changes, and substitutions. It is understood that such modifications may be made hereinbefore without departing from the scope of the present disclosure. Therefore, it is appropriate that the appended claims be broadly construed so as not to be inconsistent with the present disclosure.

Claims

1. 1. A device for treating dry eye, the device being configured to be placed under an eyelid and positioned between the eyelid and an ocular surface and worn by a user, the device comprising: a first surface configured to face a portion of the sclera of the eye and contact a surface of the eye; a second surface configured to face the eyelid and to be completely covered by the eyelid when the eyelid is open; a plurality of stimulating electrodes proximate the first surface, the plurality of stimulating electrodes configured to stimulate the scleral and / or conjunctival surface of the eye; an energy storage element coupled to the plurality of stimulation electrodes and providing power to the plurality of stimulation electrodes; and a processor configured to control a supply of energy from the energy storage element to the plurality of stimulation electrodes to stimulate the scleral and / or conjunctival surfaces of the eye; A device having

2. 2. The device of claim 1, measuring the impedance of the tear to generate a first measurement; The device further comprises a pair of electrodes configured to determine whether to apply power and a level of power to the plurality of stimulation electrodes based on the first measurement.

3. 10. The device of claim 1, wherein the plurality of stimulation electrodes includes three or more electrodes, and the processor is further configured to selectively control the supply of power from the energy storage element to different sets of the plurality of stimulation electrodes at different times to generate a pattern of stimulation.

4. 10. The device of claim 1, further comprising a plurality of heating elements proximate the second surface, the plurality of heating elements configured to heat Meybomian glands of the eyelid.

5. The device of claim 4 , wherein the processor is further configured to control the supply of power from the energy storage element to the plurality of heating elements.

6. The device of claim 4 , further comprising a heat reflective layer disposed between the plurality of heating elements and the first surface.

7. 10. The device of claim 1, further comprising an antenna configured to transfer energy to the energy storage element, the antenna configured to wirelessly receive power from an external device to charge the energy storage element.

8. 10. The device of claim 1, wherein controlling the supply of energy from the energy storage element to a plurality of stimulation electrodes comprises applying a chirp signal to at least some of the plurality of stimulation electrodes.

9. 1. A system for treating dry eye, comprising:

1. An under-eyelid device configured to be positioned between a surface of an eyelid and a surface of an eye, comprising: The under-eyelid device comprises: a first surface configured to face and contact the surface of the eye; a second surface configured to face the eyelid and to be completely covered by the eyelid when the eyelid is open; a plurality of stimulating electrodes closer to the first surface than to the second surface, the plurality of stimulating electrodes configured to stimulate the ocular surface; and an external device configured to provide power to the under-eyelid device; 13. A system comprising an under-lid device comprising:

10. 10. The system of claim 9, wherein the under-eyelid device further comprises a pair of electrodes positioned closer to the first surface than to the second surface, the pair of electrodes configured to apply a stimulus to the eyelid to induce an eyeblink.

11. 10. The system of claim 9, wherein the under-eyelid device further comprises: an energy storage element coupled to the plurality of stimulation electrodes; and an antenna coupled to the energy storage element, the antenna configured to wirelessly receive power from the external device to charge the energy storage element; The system has:

12. 10. The system of claim 9, wherein the under-eyelid device further comprises: a plurality of heating elements closer to the second surface than to the first surface, the plurality of heating elements being configured to heat the eyelid; and a processor configured to selectively heat one or more of the plurality of heating elements and selectively activate one or more of the plurality of stimulating electrodes; Including, the system.

13. 13. The system of claim 12, wherein heating one or more of the plurality of heating elements is coordinated with activating one or more of the plurality of stimulation electrodes to heat the eyelid during sclera stimulation.

14. 12. The system of claim 11, wherein the under-eyelid device further comprises: an energy storage element coupled to the plurality of stimulation electrodes; and a processor configured to control a supply of power from the energy storage element to apply a chirp waveform to at least a portion of the plurality of stimulation electrodes; Including, the system.

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