Patent Application
20180161579
This invention relates generally to extranasal stimulation devices and methods to relieve symptoms associated with various conditions such as dry eye, contact lens discomfort, blepharitis, Meibomian gland dysfunction, and headache.
Dry Eye Disease (“DED”) is a condition that affects millions of people worldwide. More than 40 million people in North America have some form of dry eye, and many millions more suffer worldwide. DED results from the disruption of the natural tear film on the surface of the eye, and can result in ocular discomfort, visual disturbance, and a reduction in vision-related quality of life. Activities of daily living such as driving, computer use, housework, and reading have also been shown to be negatively impacted by DED. Patients with severe cases of DED are at risk for serious ocular health deficiencies such as corneal ulceration, and can experience a quality of life deficiency comparable to that of moderate-severe angina.
DED is progressive in nature, and fundamentally results from insufficient tear coverage on the surface of the eye. This poor tear coverage prevents healthy gas exchange and nutrient transport for the ocular surface, promotes cellular desiccation and creates a poor refractive surface for vision. Poor tear coverage typically results from: 1) insufficient aqueous tear production from the lacrimal glands (e.g. secondary to post-menopausal hormonal deficiency, auto-immune disease, LASIK surgery, etc.), and/or 2) excessive evaporation of aqueous tear resulting from dysfunction of the Meibomian glands. Low tear volume causes a hyperosmolar environment that induces an inflamed state of the ocular surface. This inflammatory response induces apoptosis of the surface cells which in turn prevents proper distribution of the tear film on the ocular surface so that any given tear volume is rendered less effective. This initiates a vicious cycle where more inflammation can ensue causing more surface cell damage, etc. Additionally, the neural control loop, which controls reflex tear activation, is disrupted because the sensory neurons in the surface of the eye are damaged. As a result, fewer tears are secreted and a second vicious cycle develops that results in further progression of the disease (fewer tears cause nerve cell loss, which results in fewer tears, etc.).
There is a wide spectrum of treatments for DED. Treatment options include artificial tear substitutes, topical cyclosporine, omega-3 fatty acid supplements, punctal plugs and moisture chamber goggles. Patients with severe disease may further be treated with punctal cautery, systemic cholinergic agonists, systemic anti-inflammatory agents, mucolytic agents, autologous serum tears, PROSE scleral contact lenses and tarsorrhaphy. However, many of these existing treatment options are relatively invasive and/or cumbersome for a patient to use. Accordingly, it would be desirable to have an improved treatment for dry eye and other ocular conditions.
Generally, described herein are devices and methods for extranasal stimulation to treat a condition of a subject, such as dry eye, contact lens discomfort, blepharitis, Meibomian gland dysfunction, headache, etc.
In some variations, a system for treating a condition of a subject may include a stimulator configured to deliver a stimulus to external facial tissue of the subject, at least one sensor configured to detect a characteristic of the subject, and a control system in communication with the sensor and configured to adjust the stimulus at least partially based on the detected characteristic of the subject. The stimulus may activate a nerve of the subject, thereby increasing tear production. Exemplary nerves for activation include one or more branches of the ophthalmic nerve (CN VI) and the facial nerve. Additionally or alternatively, in some variations, a stimulus may energize or activate one or more facial muscles, such as the orbicularis muscle.
Similarly, in some variations, a stimulation method for treating a condition of a subject may include delivering a stimulus to external facial tissue of the subject such that the stimulus activates a nerve of the subject, thereby increasing tear production; and adjusting the stimulus at least partially based on a detected characteristic of the subject.
In some variations of the systems and methods described herein, the stimulus may include electrical stimulation, such as from a hydrogel electrode or other suitable electrode. In other variations, the stimulus may additionally or alternatively include ultrasound stimulation, such as from an ultrasound transducer. Other suitable forms of stimulation may additionally or alternatively be provided.
One or more various sensors may be configured to be detect characteristics of a subject, such as one or more symptoms of dry eye. For example, the stimulation system may include an image sensor configured to image an ocular region of the subject, and/or an electromyography sensor configured to detect facial muscle contractions. Such sensors may be configured to detect, for example, blinking data (e.g., blink rate, blink duration, and/or blink strength), eye redness, tear meniscus height, temperature of an ocular region of the subject, an indication of successful stimulation for tear production, etc.
Additionally or alternatively, in some variations, the stimulation system may include a second sensor configured to detect an environmental condition. For example, the second sensor may be configured to measure ambient light, wind, humidity, and the like which may tend to exacerbate dry eye symptoms for the subject. The control system may be further configured to adjust the stimulus at least partially based on the detected environmental condition.
In some variations, adjustment of the stimulus may be performed at least partially based on at least one of a detected characteristic of the subject and a detected environmental condition. Additionally or alternatively, adjustment of the stimulus may be performed in response to input of the subject.
Furthermore, generally, a stimulation system may include various form factors. For example, in one variation, a system for treating a condition of a subject may include eyeglasses configured to be worn by the subject, and at least one stimulator coupled to the eyeglasses and configured to deliver a stimulus to external facial tissue of the subject. In some variations, the stimulator may be disposed on a nosepad of the eyeglasses, while in other variations the stimulator may additionally or alternatively be disposed on a nasal strip coupled to the eyeglasses. The stimulus may include, for example, electrical stimulation and/or ultrasound stimulation. The stimulus may be configured to activate a nerve of the subject, thereby increasing tear production.
As another example, a system for treating a condition of a subject may include a mask configured to be worn by the subject, wherein at least a portion of the mask is conformable to external facial tissue of the subject, and at least one stimulator coupled to the mask and configured to deliver a stimulus to the external facial tissue of the subject. In some variations, the system may further include one or more heat sources coupled to the mask. The stimulus may include, for example, electrical stimulation and/or ultrasound stimulation. The stimulus may be configured to activate a nerve of the subject, thereby increasing tear production. Furthermore, in some variations, the system may include a plurality of stimulators arranged around an ocular region of the mask, such that the stimulators are configured to stimulate external facial tissue at least partially around an orbit of the subject. Such an arrangement may, for example, strengthen an orbicularis muscle of the subject.
As yet another example, a system for treating a conditions of a subject may include a handheld body, a projection coupled to the body where at least a portion of the projection is configured to conform to external facial tissue of the subject, and at least one stimulator coupled to the projection and configured to deliver a stimulus to the external facial tissue of the subject. For example, in some variations, the projection may include a concave surface, and the stimulator may be coupled to a tissue-facing side of the concave surface for stimulating the subject. Additionally, the system may include a second stimulator coupled to the tissue-facing side of the concave surface. The stimulus may include, for example, electrical stimulation and/or ultrasound stimulation. The stimulus may be configured to activate a nerve of the subject, thereby increasing tear production. In some variations, the projection may be removable, or reversibly attachable, to the handheld body.
Also described herein are other examples of stimulation systems for providing extranasal systems and carrying about the described methods, such as goggles, eyelid pads, over-the-ear stimulators such as a clip or earmuffs, and the like.
Non-limiting examples of various aspects and variations of the invention are described herein and illustrated in the accompanying drawings.
Described herein are stimulation devices and methods to relieve symptoms associated with conditions such as dry eye, contact lens discomfort, blepharitis, Meibomian gland dysfunction, ocular discomfort due to wearing contact lenses, and headache (e.g., sinus headache). For example, at least some of the stimulation devices and methods described herein may be used to increase tear production (increase in tear and/or tear component release). As another example, at least some of the stimulation devices and methods described herein may be used to retrain certain facial muscles to improve tear and/or tear component release, such as stimulation of the orbicularis muscle to improve expression of the tear component meibum. As yet another example, at least some of the stimulation devices and methods described herein may be used to improve airway passages, such as to aid a subject or patient having breathing problems (e.g., congestion), sinus headaches, etc. These and other applications of the stimulation devices and methods are described in further detail below.
As shown in the schematic of
The one or more sensors (e.g., sensors 120 and/or 140) in the stimulation device may, for example, enable real-time or substantially real-time feedback regarding a condition of the subject and/or the environment that may be used by the control system 130 to trigger and/or modify stimulation. For example, as further described below, the one or more sensors may provide data that may be used to determine whether the subject would benefit from treatment via stimulation, and/or to determine mode of stimulation (e.g., electrical, ultrasound, etc.) intensity, duration, particular stimulation pattern, location of stimulation, and/or other suitable parameters of the stimulation. As another example, the one or more sensors in the stimulation device may provide data that may be used to assess efficacy of the stimulation treatment, and/or to determine whether further adjustments or modifications to the stimulation would be beneficial to better treat the subject. Such triggering and/or modification of the stimulation to the subject may be automatically adjusted. Additionally or alternatively, the stimulus may be controlled by the subject (or other user), such as based on a manual input through a user interface.
Different variations of the stimulation device 100 may be of any suitable form factor for positioning the stimulator at an appropriate location for delivering the stimulus to the subject.
In some variations, the form factor of the device may be commonplace and/or discreet, such that stimulation to tissue of the subject may be delivered in a manner that is less likely to be noticed by others, cause embarrassment, etc. Accordingly, a subject may more easily and more frequently obtain relief, via the stimulation, for one or more conditions such as those described herein.
The stimulation device 100 may include one or more stimulator components for stimulating a nerve or other external tissue (e.g., extranasal tissue) of a subject with one or more different kinds of stimulation. For example, as further described below, the stimulation device may include one or more electrodes providing electrical stimulation, one or more transducers providing ultrasonic or other acoustic stimulation, or other suitable forms of stimulation (e.g., chemical, heat, etc.). Stimulation waveforms delivered by the stimulators described herein may be tailored for specific treatment regimens and/or specific patients.
The one or more stimulators may be located on the stimulation device to target suitable regions on or near a user's face. Suitable targets for stimulation include, for example, nerves and/or muscles of the eyelids, near the eyelids, the eyebrows, the nose between the eyes (e.g., nose bridge), and the nose below the eyeline.
In some variations, one or more stimulators may be located on the stimulation device to target and strengthen the orbicularis muscle located around the orbit of the eye. For example, a plurality of stimulators (e.g., electrical, ultrasound, etc.) may be arranged so as to stimulate an area around the orbit of the subject's face. The orbicularis muscle is the muscle that closes the eyelids. With age and/or muscular conditions, the orbicularis muscle may atrophy and make expression of meibum (a tear component) more difficult. By targeting stimulation on the orbicularis muscle, some variations of a stimulation device may strengthen and regrow the muscle for easier meibum expression. Furthermore, in some variations, stimulation of the orbicularis muscle may provide cosmetic benefits such as improved facial appearance, as the result of eyelids gaining a healthier appearance in shape and strength.
In some variations, the stimulator 110 may include at least one electrode for providing electrical stimulation to an anatomical target. The electrode may be coupled to a support structure so as to contact target tissue of the subject. For example, in the exemplary variation of an eyeglasses stimulation device 300 shown in
The stimulator 110 may, in some variations, be configured to deliver patterned stimulation waveforms (e.g., electrical stimulation) to an anatomical structure as described in U.S. Pat. No. 9,687,652 titled “STIMULATION PATTERNS FOR TREATING DRY EYE” and filed Jul. 24, 2015, which is incorporated herein in its entirety by this reference.
When patterning of stimulation waveforms is employed, waveform parameters such as the shape, the frequency, the amplitude, and the pulse width may be modulated. The frequency, pulse-width, and/or amplitude of the waveform may be modulated linearly, exponentially, as a sawtooth, a sinusoidal form, etc., or they may be modulated randomly. The stimulation can also be interrupted as part of the patterning. That is, the stimulation can be in an on/off condition, e.g., for durations of 1 second on/1 second off, 5 seconds on/5 seconds off, etc. Modulation of the waveform shape (e.g., rectangular vs. triangular vs. exponential) in a rhythmic or non-deterministic, non-rhythmic fashion may also be used. Thus, numerous variations in waveform patterning can be achieved. It should be understood that combinations of these parameter changes over time in a repetitive manner may also be considered patterning. In some instances, random patterning may be employed. Patterning may help to prevent subject habituation to the applied stimulation (i.e., may help to prevent the subject response to the stimulation decreasing during stimulation).
The stimulation may be delivered periodically at regular or irregular intervals. Stimulation bursts may be delivered periodically at regular or irregular intervals. The stimulation amplitude, pulse width, or frequency may be modified during the course of stimulation. For example, the stimulation amplitude may be ramped from a low amplitude to a higher amplitude over a period of time. In other variations, the stimulation amplitude may be ramped from a high amplitude to a lower amplitude over a period of time. The stimulation pulse width may also be ramped from a low pulse width to a higher pulse width over a period of time. The stimulation pulse width may be ramped from a high pulse width to a lower pulse width over a period of time. The ramp period may be between 1 second and 15 minutes. Alternatively, the ramp period may be between 5 seconds and 30 seconds.
It should be appreciated any of the above waveform parameters and variations in parameters may be combined to generate a patterned stimulation waveform, and these waveforms may be delivered by any of the stimulators described herein. For example, in variations where the stimulation is electrical and comprises a biphasic pulse, the biphasic pulse may have any suitable frequencies, pulse widths, and amplitudes. The stimulation amplitude, pulse width, and frequency may be the same from pulse to pulse, or may vary over time, as described in more detail herein. Combinations of these parameters may increase the efficacy and/or comfort of stimulation, and in some cases, the efficacy and/or comfort may differ by individual patient, as described in more detail herein. Exemplary patterned waveform parameters for extranasal electrical stimulators are listed below in Table 1.
It should be appreciated that electrical stimulation waveforms may be delivered via a multi-polar, such as bipolar, tripolar, quad-polar, or higher-polar configuration or a monopolar configuration with distal return. The waveforms may be a sinusoidal, quasi-sinusoidal, square-wave, sawtooth, ramped, or triangular waveforms, truncated-versions thereof (e.g., where the waveform plateaus when a certain amplitude is reached), or the like.
In variations in which electrical stimulation includes an alternating monophasic pulsed waveform, each pulse delivered by the stimulator may have a single phase, and successive pulses may have alternating polarities. Generally, the alternating monophasic pulses are delivered in pairs at a given frequency (such as one or more of the frequencies listed above, such as between 30 Hz and 80 Hz), and may have an inter-pulse interval between the first and second pulse of the pair (e.g., about 100 μs, between 50 μs and 150 μs or the like). Each pulse may be current-controlled or voltage-controlled, and consecutive pulses need not be both current-controlled or both voltage-controlled. In some variations where the pulse waveform is charged-balanced, the waveform may comprise a passive charge-balancing phase after delivery of a pair of monophasic pulses, which may allow the waveform to compensate for charge differences between the pulses.
When a stimulator configured to deliver an electrical stimulation waveform is positioned to place an electrode on either side of the nose, alternating monophasic pulses may promote bilateral stimulation of nasal tissue. The pulses of a first phase may stimulate a first side of the nose (while providing a charge-balancing phase to a second side of the nose), while the pulses of the opposite phase may stimulate the second side of the nose (while providing a charge-balancing phase to the first side of the nose), since nerves may respond differently to anodic and cathodic pulses. The inter-pulse interval may give time for the stimulation provided by a first phase pulse to activate/polarize the target nerves prior to being reversed by an opposite phase pulse.
In variations configured to deliver electrical stimulation, the stimulator may include one or more conductive materials such as metal (e.g., stainless steel, titanium, tantalum, platinum or platinum-iridium, other allows thereof, or the like), conductive ceramics (e.g., titanium nitride), liquids, and/or gels, etc. As another example, the electrode may include an electrically conductive hydrogel. The hydrogel may include any suitable hydrogel, such as those described in U.S. Pat. No. 9,770,583 titled “POLYMER FORMULATIONS FOR NASOLACRIMAL STIMULATION” filed Feb. 24, 2015, which is incorporated herein in its entirety by this reference. The conductive material of the stimulator may be coupled to stimulator circuitry and/or other aspects of the control system via one or more conductive leads (e.g., wires) or conductive traces.
Additionally or alternatively, ultrasonic energy may be delivered to external tissue by a stimulator comprising one or more ultrasound transducers. For example, one or more pulses of air may be delivered to stimulate tissue. The pulses of air may be generated via a source of compressed gas (e.g., air), or the like. In some variations, the gas may be warmed or cooled (e.g., mechanically or via one or more thermally-activated fibers). In some variations, the ultrasonic energy may be focused so as to concentrate the energy into a small focal zone in the target stimulation region. For example, the ultrasonic energy may be focused by an acoustic lens, a curved transducer, and/or a phased array, etc.
In other variations, one or more portions of a stimulator may be a heating source to provide thermal stimulation to tissue, such as with a resistive element that is activated to generate heat. Additionally or alternatively, one or more portions of a stimulator may include a cooling source (e.g., gel) to provide another form of thermal stimulation to tissue. In yet other variations, the stimulator may additionally or alternatively use one or more light-generating or magnetic field-generating elements to stimulate tissue. In yet other variations, a stimulator may include chemical stimulation (e.g., by releasing a chemical agent providing a chemical stimulus).
As shown in
Additionally or alternatively, information detected by the sensors 120 and/or 140 may be used to develop an adaptive learning algorithm that associates particular subject characteristics and/or environmental conditions with dry eye symptom severity (for an individual and/or for general populations). Other examples of adaptive algorithms are described below with respect to the control system.
Generally, in some variations, at least one sensor 120 may be configured to detect a characteristic of the subject relating to dry eye symptoms and/or symptoms of other ocular conditions. The control system may adjust the stimulation in response to this indication of dry eye symptoms.
In some variations, the sensor 120 may include an image sensor. For example, in the exemplary variation of an eyeglasses stimulation device 300 shown in
The image sensor 320 may be configured to detect, for example, one or more parameters related to blinking, such as blink rate, blink duration, and blink strength. An act of blinking may be determined based on detected movement of an upper eyelid and/or lower eyelid, and/or detected change in exposed surface area of an eye of the user. For example, such eyelid movement and/or change in exposed surface area of an eye may be determined using suitable machine vision techniques (e.g., edge detection). As another example, markers (e.g., IR markers) may be attached to facial skin (e.g., eyelids, eyebrows, etc.), and an IR camera system may track the movements of the markers to detect blinking parameters. Blinking data may be correlated to severity of dry eye symptoms. For example, in some variations, if the subject is blinking at a higher frequency, blinking for longer duration, and/or blinking more strongly, the subject may be experiencing more severe dry eye symptoms. Accordingly, blinking data may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms. Similarly, blinking data may provide a basis for triggering stimulation that reminds the subject to blink when he or she has not blinked after a predetermined time or with at least a predetermined frequency. Stimulation for reminding the subject to blink may be similar to stimulation for increasing tear production, or may be specifically designed for reminder purposes (e.g., higher frequency, larger amplitude, shorter duration, etc. compared to stimulation for increasing tear production). Additionally or alternatively, the stimulation system may be configured to provide the subject with reminders to blink using other suitable mechanisms, such as vibration and/or audio.
Additionally or alternatively, the image sensor 320 may be configured to detect changes in blood vessels in the subject's eye. For example, an optical image from the image sensor may be analyzed via machine vision techniques applied to pixel colors, in order to measure eye redness of the subject. Eye redness may generally indicate forms of stress, irritation, etc. in the ocular region. For example, the intensity of localized redness, average redness of the subject's sclera, the pattern of redness across the surface of the eye, and/or other parameters relating to eye redness may be correlated to severity of dry eye symptoms. Accordingly, eye redness may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms and other conditions.
As another example, the image sensor 320 may be configured to detect tear meniscus height (e.g., tear meniscus on the lower eyelid of the subject). For example, an image from the image sensor may be analyzed via machine vision techniques (e.g., edge detection) to measure height of the tear meniscus. In one exemplary embodiment, tear meniscus height may be measured as the distance between a tear meniscus and a lower eyelid of the subject (both detected, for example, using edge detection techniques on an optical image or a thermal image). Tear meniscus height may vary according to severity of dry eye in the subject. For example, if the user has a smaller tear meniscus, the subject may be experiencing more severe dry eye symptoms. Accordingly, tear meniscus height may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms and other conditions.
As yet another example, the image sensor 320 may be used to measure tear film breakup time (TBUT) as an indication of dry eye symptoms. For example, with the subject not blinking, the image sensor 320 may monitor the tear film over time as evaporation causes the tear film to thin and eventually form dry spots due to insufficient wetting on the surface of the eye. The time that it takes for the first dry spot to form is referred to as the TBUT, where shorter TBUT times may be correlated to severity of dry eye symptoms. In some variations, as determining TBUT, dry spot formation may be identified with machine vision techniques applied to an image of the eye taken by the image sensor 320. For example, reflectivity or glossiness over the surface of the eye (e.g., as captured in an optical image by an optical camera) may be analyzed by applying machine vision techniques, and may be correlated to dry eye symptoms. In some variations, a fluorescine dye may be applied to the surface of the eye and mixed with tear film to better distinguish wet spots from dry spots. As another example, temperature distribution over the surface of the eye (e.g., as captured in a thermal image by an IR camera) may be analyzed and correlated to dry eye symptoms. Additionally or alternatively, TBUT may be determined by direct inspection (e.g., by a clinician) of the image and/or the subject's eye itself. Accordingly, tear film breakup time may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms and other conditions.
As another example, the image sensor may be configured to assess temperature of the ocular region, such as the cornea, conjunctive, and lower and/or upper eyelid. Temperature of any one or more areas of the ocular region may be measured, for example, using an IR image sensor generating a thermal image of the ocular region. Generally, a lower temperature in the ocular region (e.g., ocular surface) may correspond to decreased tear production (e.g., due to more rapid cooling observed in patients with dry eye symptoms compared to healthy patients). For example, in some variations, in response to detecting an ocular region (e.g., ocular surface) temperature that is below a predetermined threshold, and/or an ocular region (e.g., ocular surface) temperature drop that is greater than a predetermined threshold (e.g., between about 0.5 degrees Celsius and about 1.0 degree Celsius, or other suitable values), stimulation may be triggered or stimulation intensity may be increased. Accordingly, temperature of the ocular region may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms and other conditions.
In some variations, the sensor 120 may include an electromyography (EMG) sensor configured to detect electrical activity produced by skeletal muscles. The EMG sensor may, for example, include an adhesive backing that allows the EMG sensor to couple to the skin of the subject proximate a muscle of interest. Alternatively, the EMG sensor may be coupled to a device (e.g., mask) that positions the EMG sensor against the skin of the subject. Leads from the EMG sensor, or another suitable communication scheme, may communicate signals from the EMG sensor to the control system for processing. For example, one or more EMG sensors may be disposed across the nose bridge of the subject and/or in the region between the subject's nose and ear, such that data from the EMG sensors may be used to determine whether the subject is blinking very strongly with his or her muscles in the nasal region. As described above, blink strength may be correlated to severity of dry eye symptoms. Accordingly, EMG data may provide a basis for adjusting stimulation in order to provide the subject with suitable relief of dry eye symptoms and other conditions.
As another example, one or more EMG sensors may be disposed along the jaw or cheek of the subject, such that data from the EMG sensors may be used to determine whether the subject is yawning. Since yawning often triggers tearing in healthy individual, EMG data may provide a basis for adjusting stimulation in order to provide the subject with appropriate tear production corresponding to the subject's yawning, particularly if the subject is experiencing symptoms of dry eye, Meibomian gland dysfunction, and/or blepharitis.
Additionally or alternatively, in some variations, at least one sensor 120 may be configured to detect a characteristic of the subject indicating successful stimulation. Accordingly, data from the sensor 120 may be used to confirm, for example, whether tear production has occurred. The control system may utilize this information as feedback to modify the stimulation to be delivered to the subject (if, for example, tear production has not occurred) until successful stimulation has been detected. Additionally or alternatively, the control system may maintain settings, such as frequency, pattern, intensity, and the like, for the stimulation delivered to the subject (if, for example, tear production has successfully occurred).
For example, in some variations, at least one sensor 120 may include an image sensor (e.g., similar to image sensor 320 as described above) configured to detect a dilation and constricting of the iris. For example, an image from the image sensor may be analyzed via machine vision techniques in order to determine whether the diameter of an iris of the subject's eye has increased and then decreased. The iris may open and close in response to stimulation. Accordingly, such fluctuation of the subject's iris may be an indication of successful stimulation.
Furthermore, any of the subject characteristics described above as being correlated to dry eye symptoms may also indicate successful stimulation, when such symptoms are reduced. For example, detection of reduced blink rate, reduced blink duration, and/or reduced blink strength (e.g., as detected by an image sensor and/or EMG sensor as described above, or other suitable sensor) may indicate successful stimulation to achieve increased tear production. As another example, decreased eye redness (e.g., as detected by an image sensor as described above) may indicate successful stimulation. As yet another example, increased tear meniscus height (e.g., as detected by an image sensor as described above), may indicate successful stimulation. Furthermore, an increase in temperature in the ocular region (e.g., as detected by an image sensor as described above) may be correlated to increased tear production and thus may indicate successful stimulation.
Although image sensors and EMG sensors are described above as detecting one or more characteristics such as blinking parameters, changes in blood vessels in the subject's eye, and tear meniscus height, it should be understood that these characteristics may be detected and measured with any suitable sensor arrangement. Furthermore, information from multiple sensors may be collected and compared in order to corroborate conclusions about severity of dry eye symptoms and/or success of stimulation, thereby improving accuracy of the assessment of the subject and improving the efficacy of the stimulation device for the subject.
Generally, in some variations, at least one sensor 140 may be configured to detect an environmental condition, such as an environmental condition that may cause or exacerbate dry eye symptoms. The control system may adjust the stimulation in response to such an environmental condition, such as to automatically trigger or modify the stimulation to increase tear production in the subject. Such stimulation may, for example, help provide relief of dry eye symptoms and/or pre-emptively reduce the likelihood of dry eye symptoms. Additionally, information from multiple sensors may be useful for developing more accurate adaptive algorithms for stimulation, as further described below.
For example, in the exemplary variation of an eyeglasses stimulation device shown in
Similarly, in some variations, the light sensor 340 may detect changes in light as the subject (while wearing the stimulation device 300) moves around and enters brightly-lit areas. For example, if detected light intensity exceeds a predetermined threshold, then the measurement may indicate that the subject has moved to a brighter environment. Similarly, a magnitude of change in detected light intensity that exceeds a predetermined threshold may indicated that the subject has moved to a brighter environment. When the subject moves to a brightly-lit area, he or she may experience photophobia or other forms of photosensitivity. Simulation by the stimulation device may, in some variations, reduce such photophobia. Accordingly, detected changes in light may provide a basis for adjusting stimulation in order to provide the subject with suitable relief and/or pre-emptive reduction of photophobia.
Additionally or alternatively, in some variations of a stimulation device including an image sensor, the light sensor 340 or another image sensor may provide data regarding ambient light so as to calibrate or normalize images from the image sensor. For example, the light sensor 340 may be used to subtract effects of ambient light on an optical image taken by the one or more image sensors 320. For example, reference pixel color values (e.g., red, green, and blue (RGB) intensity values) associated with ambient light may be determined from a reference image (e.g., an image taken of a reference surface with known characteristics). In order to compensate for effects of ambient light on an optical image of interest taken by the one or more image sensors 320, these reference pixel color values may be subtracted from the optical image of interest. However, other suitable manners of compensation for ambient light and/or other suitable calibration may be performed.
In other variations, other sensors 140 may be configured to detect other environmental conditions. For example, in the exemplary variation of an eyeglasses stimulation device shown in
In some variations, the sensor 342 may include a humidity sensor configured to detect ambient humidity. A low humidity environment may be correlated to an increased likelihood of dry eye symptoms and/or increased severity of dry eye symptoms. For example, low humidity may be detected when the subject is in an arid climate, in an air-conditioned or heated room or vehicle, etc. and may be at greater risk of experiencing dry eye symptoms. Accordingly, detected humidity may provide a basis for adjusting stimulation in order to provide the subject with suitable relief and/or preemptive reduction of dry eye symptoms.
The sensor 342 may additionally or alternatively include a pressure sensor configured to detect a windy environment. A windy environment may increase evaporation rate of tear film from a subject's eyes and increase likelihood and/or severity of dry eye symptoms. Accordingly, detected pressure correlated to wind may provide a basis for adjusting stimulation to relieve and/or preemptively reduce dry eye symptoms.
In some variations, the sensor 342 may include an accelerometer, an inertial measurement unit (IMU), a barometer, or other suitable sensor that may indicate when the subject is traveling in a type of vehicle that is often associated with an environment more likely to cause dry eye symptoms. For example, certain levels of acceleration and/or velocity measured by an accelerometer or IMU may, if exceeding a predetermined threshold, indicate that the subject is likely sitting in a car, bus, airplane, or other vehicle that often has a drier, air-conditioned environment. Similarly, a barometer may detect air pressure changes that may indicate that the subject is likely sitting in an airplane. As yet another example, an audio sensor may detect certain audio frequencies associated with plane travel, car travel, etc. Accordingly, detected acceleration, velocity, and/or air pressure changes, etc. may provide a basis for adjusting stimulation to relieve and/or preemptively reduce dry eye symptoms.
Although various sensors are described above as detecting one or more environmental conditions, it should be understood that these conditions may be detected and measured with any suitable sensor arrangement. Furthermore, information from multiple sensors may be collected and compared in order to corroborate conclusions about environmental conditions, thereby improving accuracy of the assessment of the environment and assessment of whether stimulation for tear production would be beneficial for the subject. Additionally, information from multiple sensors may be useful for developing more accurate adaptive algorithms for stimulation, as further described below.
Generally, the control system 130 may be configured to control a stimulus to be delivered to a subject via the stimulator. As shown in
The control system 130 may include circuitry and other suitable components configured to operate the stimulators and/or sensors as described herein. In some variations, the control system 130 may include a processor 132, memory 134, and/or a stimulation controller 136. The processor 132 may be configured to control operation of the various components of the control system 130 and/or analyze sensor data. For example, the processor 132 may be configured to receive data regarding one or more characteristics of the subject, and/or one or more environmental conditions and determine whether and how the stimulator will deliver stimulation the subject (e.g., as described above). Generally, the processor 132 may, for example, provide commands to the stimulation controller 134 to control parameters of the stimulation. The memory 134 may be configured to store programming instructions for the processor 132 to use in providing commands to the stimulation controller 134 to operate the stimulator. The stimulation controller 134 may be configured to generate a stimulation signal (e.g., waveform signal) and deliver the stimulation signal to the stimulator.
Some or all of the control system 130 may be included in a wearable device (e.g., eyeglasses as shown in
In some variations, the memory 134 may be configured to store information (e.g., sensor data) that was detected before, during, and/or after stimulation. This information may, for example, be used during execution of programming instructions for adjusting stimulation. Additionally or alternatively, the information may be used to create a medical record of the subject, such as for identifying patterns of the subject's symptoms for various activities, identifying trigger events (e.g., wind as a greater contributor to a particular subject's dry eye symptoms compared to ambient light changes), and the like. Furthermore, the stored information may be used as part of an adaptive learning algorithm, as described below.
Even further, in some variations, the memory 134 (or another storage device) may be configured to store preferences of the subject relating to stimulation. For example, the memory 134 may store one or more preferred stimulation patterns (e.g., preferred intensity that is both comfortable and known to the subject for successfully causing tear production). One or more of the preferred stimulation patterns may be associated with a particular activity or environment, such that the control system triggers a preferred stimulation pattern when the system detects or is notified that the subject is engaging in that activity or in that environment. As another example, the memory 134 may be configured to store one or more stimulation schedules that are preferred by the subject over the course of a typical day (e.g., frequency of treatment sessions).
The memory 134 may store programming instructions for adjusting stimulation based at least in part on the detected characteristics of the subject and/or detected environmental conditions. For example, the control system 130 may be configured to compare the detected characteristics and/or detected environmental conditions, individually and/or in combination, to one or more predetermined thresholds. Such a comparison may involve, for example, a table lookup and/or parametric model, using a table or formula stored in memory 134 or received from another storage medium. Depending on result of the comparison performed, the processor may provide commands to the stimulation controller 134 to provide stimulus signals to operate the one or more stimulators accordingly. For example, the control system 130 may be configured to trigger or increase stimulation (e.g., increase intensity) in response to sensor data generally associated with dry eye symptoms, environmental conditions likely to increase dry eye symptoms, and/or unsuccessful stimulation for tear production.
Additionally or alternatively, in some variations the control system 130 may be configured to adjust stimulation based at least partially on temporal conditions. For example, the control system 130 may be configured to trigger or increase stimulation periodically (e.g., provide stimulation every 10 minutes, every 30 minutes, every hour, etc.). As another example, the control system 130 may be configured to trigger or increase stimulation after the passage of a predetermined amount of time since the occurrence of the most recent stimulation (e.g., provide stimulation if the most recent stimulation occurred 10 minutes ago, 30 minutes ago, an hour ago, etc.), which may or may not have been at least partially based on sensor data gathered as described herein. In yet other example, the control system 130 may be configured to adjust stimulation based on the time of day. In some variations, stimulation during the day (e.g., during business hours) may be different than stimulation during the evening (e.g., after business hours). For example, stimulation during the day may energize or activate a target nerve or other target tissue to a greater extent (e.g., have higher intensity) compared to stimulation during the evening.
In some variations, the control system 130 may be configured to trigger or increase stimulation at least partially based on the occurrence, or in anticipation of, a predetermined event. For example, the control system 130 may be synced to a subject's calendar such that certain kinds of events (e.g., business meeting, air travel, etc.) that may result in increased severity of dry eye symptoms may serve as a basis for adjusting the stimulation for the subject. Such adjustment may, for example, involve triggering stimulation according to stored preferred stimulation patterns (e.g., for particular environments).
As another example, the control system 130 may additionally or alternatively be configured to adjust stimulation based at least in part on one or more adaptive learning algorithms (e.g., machine learning algorithms). For example, in some variations, a predictive model for assessing symptom severity for a particular subject (or set of similar subjects) may be developed based on subject characteristics and/or environmental conditions. Such a predictive model may be trained using empirical training data for the subject (or similar subjects). The predictive model may, for example, be trained using one or more suitable machine learning algorithms (e.g., regularized multi-variate regression algorithm, any suitable supervised or unsupervised machine learning algorithm such as a neural network algorithm, decision tree, etc.). In some variations, the predictive model may be continually updated or trained based on new sensor data from the stimulation device.
In one illustrative example, the control system 130 may be configured to adjust stimulation in accordance with an adaptive learning algorithm that assesses the subject's dry eye severity based on blinking data (e.g., blink frequency, blink duration, blink strength, etc.) and/or eye redness data collected over time (e.g., as the subject wears eyeglasses shown in
As yet another example, the control system 130 may additionally or alternatively be configured to adjust stimulation at least based on user input via a user interface. One example of a user interface for a stimulation device is shown in
Although the sensor and control systems are primarily described herein for use with extranasal stimulation, it should be understood that in other variations, similar sensor arrangements and/or control schemes may be used in combination with other forms of stimulation. For example, stimulation may be provided intranasally. Exemplary intranasal stimulation devices are described in U.S. Pat. No. 8,996,137 titled “NASAL STIMULATION DEVICES AND METHODS” and filed Apr. 18, 2014 which is incorporated herein in its entirety by this reference. As another example, stimulation may be provided via a microstimulator implant implanted intranasally, in an orbit of an eye, or other suitable location. Exemplary microstimulator implants are described in U.S. Pat. No. 9,821,159 titled “STIMULATION DEVICES AND METHODS” and filed Apr. 6, 2012, which is incorporated herein in its entirety by this reference.
At least a portion of the eyeglasses may be adjustable to conform or otherwise fit the face of the subject. For example, the bridge of the eyeglasses frame may be adjustable (e.g., flexible plastic or wireframe) to suitably contour the eyeglasses frame to the front of the subject's face. As another example, the arms of the eyeglasses frame may be adjustable to securely couple around the ears of the subject. The lenses of the eyeglasses may, in some variations, provide vision correction (e.g., correction for near-sightedness, far-sightedness, astigmatism, etc.). Alternatively, one or both of the lenses may be blank lenses not providing vision correction (e.g., non-prescriptive).
In some variations, the stimulators 310 may include conductive hydrogel electrode pads disposed on the nose bridge of the eyeglasses, one hydrogel pad for stimulating each side of the subject's nose. The hydrogel pads may be removable from the eyeglasses, such as to be replaceable. Different sizes of electrode pads may be provided so as to accommodate a variety of sizes and shapes of noses. The hydrogel may include any suitable hydrogel, such as those described in U.S. Pat. No. 9,770,583 titled “POLYMER FORMULATIONS FOR NASOLACRIMAL STIMULATION” filed Feb. 24, 2015, which is incorporated herein in its entirety by this reference. In other variations, the stimulators 310 may include other suitable conductive surfaces. In some variations, the electrodes may deliver electrical stimulation as described in U.S. Pat. No. 9,687,652 titled “STIMULATION PATTERNS FOR TREATING DRY EYE” and filed Jul. 24, 2015, which is incorporated herein in its entirety by this reference, or other suitable stimulation.
In some variations, the nasal strip 1002 may include one or more stimulators 1010 (e.g., electrodes, ultrasound transducers), including at least one stimulator 1010 disposed on each side of the nasal strip for stimulating a left side and a right side of the subject's nose. For example, the stimulators 1010 may be coupled to a tissue-facing side of the nasal strip 1002 via adhesive, hooks, or any suitable mechanism. The stimulators 1010 may be electrically connected via leads to a power supply and/or a control system on the eyeglasses. In some variations, the stimulators may be configured to stimulate tissue to induce mucin production in the eye, mucous production in the nose, remove old mucous from nose, etc., thereby improving congestion of the subject.
Additionally or alternatively, the nasal strip may be a nasal dilator by pulling on the outside tissue and thereby keeping the breathing passage open and improving nasal congestion. In some variations, the nasal strip and its stimulators may be a standalone device by omitting the eyeglasses. For example, in these variations, instead of connecting to a power supply and/or control system on eyeglasses, a power supply (e.g., battery) and a control system may be disposed on the nasal strip itself. Alternatively, stimulators 1010 on the nasal strip may receive power and/or control signals from a remote control system through wireless communication.
The housing 402 may be contoured to complementarily receive the face of the subject. For example, the housing 402 may include an eye shroud that includes a concave profile that conforms to the face of the subject. As another example, the housing 402 may include a flexible eye shroud (e.g., made of rubber or flexible plastic) that flexes to conform to the face of the subject. In some variations, the flexible eye shroud may form a substantially airtight seal against the face of the subject so as to help reduce evaporation of tear film from eyes of the subject.
The stimulation device 400 may additionally include one or more stimulators 410 (e.g., electrodes, ultrasound transducers, etc.) disposed on the interior of the housing and proximate the face of the subject. The stimulators 410 may, for example, line at least a portion of an interior portion of the housing 402 and/or viewing window 404 so as to contact or face the external facial skin of the subject. In some variations, the stimulators 410 contact the skin of the subject around an orbit, so as to stimulate the orbicularis muscle of the subject. As described above, periodic stimulation of the orbicularis muscle may retrain the muscle for rehabilitation and/or regrow the muscle mass for improved muscle strength, such as for easier meibum expression. In some variations, the stimulators 410 may additionally or alternatively improve facial appearance as the eyelids become more healthy-looking in shape and appearance. The stimulators 410 may be controlled by a control system (not shown) which may adjust the stimulation based on sensor data and/or in response to a user input.
The stimulation device 400 may additionally or alternatively include one or more heating sources 412 (e.g., resistive elements, thermal heating gel, etc.) disposed in the housing and configured to be positioned proximate the face of the subject. In some variations, the stimulation 400 may further include one or more cooling sources. Furthermore, the stimulation device 400 may additionally or alternatively include one or more massaging elements 414, such as beads or mechanically actuated projections. The heating sources, cooling sources, and/or massaging elements may be configured to relax the orbicularis muscle and thereby improve meibum expression.
Stimulators 510, heating sources 512, cooling sources, and/or massaging elements 514 may be distributed across the stimulation device 500. For example, as shown in
In some variations, as shown in
As shown in
The stimulus may be delivered to a subject via the projection region 1104. In some variations the body 1102 and projection region 1104 may be reversibly attachable. Some or all of the stimulator 1100 may be disposable, and some or all of the stimulator 1100 may be reusable. For example, in variations where the projection region 1104 is releasably connected to the body 1102, the body 1102 may be reusable, and the projection region 1104 may be disposable and periodically replaced. In some of these variations, the device may include a disabling mechanism that prevents stimulus delivery to the subject when the projection region 1104 is reconnected to the body after being disconnected from the body. Additionally or alternatively, the device may include a lockout mechanism that prevents the projection region 1104 from being reconnected to the stimulator body after being disconnected from the stimulator body. In some variations, as shown in
The projection region 1104 may include at least one prong 1106, which may be configured to be placed in contact with, or proximate to, external facial tissue of the subject. In the handheld stimulator variation shown in
In some variations, the projection region 1104 may include an alignment feature to help the subject appropriately position the prongs 1106 and 1108 on his or her external facial tissue. For example, the projection region 1104 may include a stop (e.g., located between the prongs) configured to abut a distal tip of the subject's nose. Alignment of the stop against the distal tip of the subject's nose may help appropriately position stimulators 1110 and 1112 against a target region for stimulation. In some variations, as shown in
The projection region 1104 may comprise at least one stimulator (e.g., electrode, ultrasound transducer, etc.). For example, as shown in
As shown in the cut-away view of the stimulator 1100 in
The body may comprise a user interface 1130 comprising one or more operating mechanisms to adjust one or more parameters of the stimulus. The operating mechanisms may provide information to the control subsystem 1136, which may comprise a processor, memory, and/or stimulation controller as described above. In some variations, the operating mechanisms may comprise first and second buttons, as illustrated for example in
As shown in
As shown in
In some variations, the projection 1204 may include an alignment feature to help the subject appropriately position the projection 1204 on his or her external facial tissue. For example, the projection region 1204 may include a stop such as a ridge 1205 located along the bottom of the projection 1204 and configured to abut a distal tip of the subject's nose. Alignment of the stop against the distal tip of the subject's nose may help appropriately position stimulators 1110 and 1112 against a target region for stimulation.
As shown in
As shown in
Similar to the stimulators 1410 described above with reference to
Generally, in some variations, as shown in
In some variations, the method 1600 may include detecting at least one of a characteristic of the subject and an environmental condition 1610. The detected subject characteristic and/or environmental condition may serve as a basis for adjusting the stimulus. For example, suitable characteristics of a subject include one or more symptoms of dry eye (e.g., blink rate, blink duration, blink strength, eye redness, tear meniscus height, temperature, etc.), and/or one or more indications of successful stimulation for tear production. Sensors such as image sensors and electromyography sensors may be used to detect (e.g., measure) such subject characteristics. Suitable environmental conditions to serve as a basis for adjusting the stimulus include, for example, ambient light, humidity, wind conditions, air pressure, and other environmental conditions described above. The method may include triggering onset of stimulation (e.g., stimulation in accordance with a stimulation intensity preferred by the subject) or otherwise adjusting stimulation (e.g., increasing intensity of stimulation) in response to detecting one or more dry eye symptoms and/or detecting one or more environmental conditions that may cause and/or exacerbate dry eye symptoms.
In some variations, adjusting the stimulus 1630 may be performed according to an adaptive learning algorithm. For example, as described above, in some variations, a predictive model for assessing symptom severity for a particular subject (or set of similar subjects) may be developed based on subject characteristics and/or environmental conditions. Such a predictive model may be trained using empirical training data for the subject (or similar subjects). The predictive model may, for example, be trained using one or more suitable machine learning algorithms (e.g., regularized multi-variate regression algorithm, any suitable supervised or unsupervised machine learning algorithm such as a neural network algorithm, decision tree, etc.). In some variations, the predictive model may be continually updated or trained based on new sensor data from the stimulation device.
In one illustrative example, the method 1600 may include adjusting stimulation in accordance with an adaptive learning algorithm that assesses the subject's dry eye severity based on blinking data (e.g., blink frequency, blink duration, blink strength, etc.) and/or eye redness data collected over time (e.g., as the subject wears eyeglasses as shown in
Stimulation was performed using a handheld stimulator as shown in
Participants were subjected to extranasal stimulation for three minutes using a handheld stimulator shown in
The participants were instructed to place the tips of the handheld stimulator on the lower part of the nose (one tip on each side) for extranasal stimulation, as shown in
Data illustrating the decrease in IL-8 concentration as compared to controls after extranasal stimulation application are provided in
Participants included 48 adults with mild to severe dry eye disease, baseline Ocular Surface Disease Index® ≥13, Schirmer test (with anesthesia) ≤10 mm and cotton swab nasal stimulation Schirmer test ≥7 mm higher in the same eye. As part of the study, participants were subjected to extranasal stimulation for three minutes using a handheld stimulator as shown in
Participants included 25 dry eye subjects. As part of the study, tear meniscus height was measured prior to and immediately following about 2 minutes of extranasal stimulation using a handheld stimulator as shown in
The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that specific details are not required in order to practice the invention. Thus, the foregoing descriptions of specific embodiments of the invention are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed; obviously, many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to explain the principles of the invention and its practical applications, they thereby enable others skilled in the art to utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention.
This application claims priority to U.S. Patent Application Ser. No. 62/429,065, filed on Dec. 1, 2016, which is incorporated herein in its entirety by this reference.
| Number | Date | Country | |
|---|---|---|---|
| 62429065 | Dec 2016 | US |
