Tear stimulator

Abstract

The present invention provides a tear stimulation device and method that delivers thermal energy at a controlled rate to stimulate natural tear production by activating thermoreceptors in the sensory nerves and extended orbital region of the eye, and modulating the thermal energy results in a naturally lubricated and nutritious environment in which tears can be produced repeatedly and in a controlled manner to heal the ocular surface.

Description

[Technical field]

[0001] The present invention provides tear stimulation devices and methods, particularly devices and methods that are comfortable to use and thus ensure the secretion of a regular supply of natural tears during sleep to treat or avoid dry eye and other conditions associated with or caused by a deficiency of natural tears. [Background technology]

[0002] To function properly, the cornea (the surface of the eye) requires continuous lubrication by tears, both while awake and asleep. The tear film and cornea together provide 65% of the eye's focusing power. To maintain optical quality, the tear film must be constantly replenished by natural tear secretion. Otherwise, the tear film becomes unstable and the ocular surface of the eye becomes damaged by drying.

[0003] The intact tear film is composed of three layers that come from three different sources: · Inner mucin layer made up of goblet cells Aqueous layer formed by lacrimal glands The outer lipid layer made up of meibomian glands

[0004] Goblet cells are located in the conjunctiva, the tissue that lines the eyelids and covers the sclera (the white of the eye). There is one lacrimal gland in each eye, located above the eyeball and below the eyebrow. There are also small accessory lacrimal glands in this area that also contribute to the aqueous layer of tears. The meibomian glands are located along the edge of the eyelids and inside the eyelashes. There are approximately 40-50 meibomian glands in the upper eyelid and 20-25 in the lower eyelid.

[0005] It is known that the application of heat to the eyelids can be used to melt lipids in the meibomian glands and specifically improve secretion from the meibomian glands. This outer lipid layer of the tear fluid improves the symptoms of dry eye by preventing evaporation of the inner (aqueous, mucinous) layers from the surface of the eye.

[0006] Individuals with dry eye do not have a sufficient amount of tear lubrication for a variety of reasons. This can lead to pain, blurred vision, eye infections and anxiety. The traditional daytime treatment for this condition is the manual application of eye drops with various mechanisms of action including lubricants, antioxidants, anti-inflammatories, stimulants, steroids and biologics.

[0007] Despite all these daytime treatments, 56% of patients say their dry eye disease (DED) symptoms remain the same or become more severe. One reason for this is that DED is not addressed during sleep, most commonly at night, when damage to the ocular surface can occur at night, when tear replenishment is generally not possible.

[0008] Current treatment options that attempt to address the problem of insufficient lubrication are classified as tear replacement, tear conservation, and tear stimulation. Tear replacement includes the artificial application of artificially formulated eye drops, ointments, or gels. Tear conservation includes punctal plugs (invasive implants to block the drainage pathway from the eye) and moisture goggles worn to create a closed moist environment around the eye. Tear conservation is primarily based on the presence of sufficient tears to be conserved. Tear stimulators attempt to stimulate the lacrimal glands by electrical, pharmacological, or ultrasonic means that are applied externally, invasively, or manually.

[0009] Tear replacement does not use natural tears, is difficult to apply to the eye, has associated risks with application, and affects vision during use. Tear conservation relies on the ability to produce sufficient tears or requires tear replacement as described above. Some methods are invasive.

[0010] Current tear stimulators are invasive and typically involve the introduction of a medical device into the body, either applied to the cornea, which must be done manually while awake, applied to the nose, which must be done manually while awake, or implanted under the skin, which requires a surgical procedure.

[0011] It is therefore an object of the present invention to address the above-mentioned problems by providing a tear stimulation device and method that is non-invasive, comfortable to wear, and can be utilized during sleep as well as while awake. Summary of the Invention

[0012] According to a first aspect of the present invention there is provided a tear stimulation device comprising a housing, a controller, a power source and one or more energy terminals arranged about the housing for transferring thermal energy to and from thermally responsive areas of the face such as to induce or increase involuntary activation of tear production, the controller being arranged to cycle the temperature of the one or more energy terminals to deliver successive heating and cooling phases, the controller being arranged in at least one cooling phase to reduce the temperature of the one or more energy terminals at a rate of between 0.01°C / s and 43°C / s, more preferably between 3°C / s and 25°C / s and most preferably between 5°C / s and 20°C / s.

[0013] Preferably, the controller is arranged to maintain a constant temperature at the one or more energy terminals during one or more of the heating and / or cooling phases over a period between 1 second and 6000 seconds, more preferably between 1 second and 120 seconds, and most preferably between 1 second and 60 seconds.

[0014] Preferably, the controller is arranged to set the temperature at the one or more energy terminals between 0°C and 48°C, more preferably between 5°C and 40°C, and most preferably between 10°C and 35°C.

[0015] Preferably, the controller is arranged to modulate the cycle frequency and / or intensity of the thermal energy.

[0016] Preferably, the controller is arranged to vary the rate of temperature change during at least one cooling phase and / or between different cooling phases.

[0017] Preferably, the controller is arranged to cause a pulsed temperature change of one or more energy terminals during at least a portion of at least one cooling phase.

[0018] Preferably, the controller is arranged to cycle the thermal energy between successive heating and cooling phases at a frequency of two or more phases per hour, more preferably two or more phases per 10 minutes, and most preferably two or more phases per 3 minutes.

[0019] Preferably, one or more of the energy terminals comprises a thermoelectric cooler.

[0020] Preferably, the one or more energy terminals are positioned to apply thermal energy to the region of or adjacent one or more lacrimal glands or the supraorbital foramen.

[0021] Preferably, the tear stimulation device comprises one or more temperature sensors located at or adjacent to one or more of the energy terminals.

[0022] Preferably, the housing comprises a support operable to releasably secure the device to a user or to clothing worn by the user.

[0023] Preferably the support comprises a headband.

[0024] Preferably, the one or more energy terminals comprise one or more energy transfer interfaces operable to deliver thermal energy to the temperature responsive region.

[0025] Preferably, the controller is operable to process data from the one or more sensors to implement feedback control of the apparatus.

[0026] Preferably, the one or more energy terminals comprise one or more energy transmission interfaces operable to deliver energy to the target area.

[0027] Preferably, the one or more energy transfer interfaces are integrally formed with the housing.

[0028] Preferably, the one or more energy transmission interfaces are operable to deliver energy to the target area without contacting the target area.

[0029] Preferably, the one or more energy transmission interfaces are operable to deliver energy to the target area while in contact with the target area.

[0030] Preferably, the one or more energy transfer interfaces comprise one or more contact pads.

[0031] Preferably, one or more of the contact pads includes a deformable element.

[0032] Preferably, one or more of the energy transfer interfaces comprises a heat transfer medium.

[0033] According to a second aspect of the present invention there is provided a method of tear stimulation comprising the steps of applying one or more energy terminals to a thermally responsive area of ​​the face and transferring thermal energy to and from the thermally responsive area via the one or more energy terminals to successively heat and cool the thermally responsive area, wherein at least one cooling phase reduces the temperature of the one or more energy terminals at a rate of from 0.01°C / s to 43°C / s, more preferably from 3°C / s to 25°C / s, and most preferably from 5°C / s to 20°C / s.

[0034] Preferably, the method comprises maintaining the one or more energy terminals at a constant temperature during one or more of the heating and / or cooling phases for a period between 1 second and 6000 seconds, more preferably between 1 second and 120 seconds, and most preferably between 1 second and 60 seconds.

[0035] Preferably, the method comprises setting the temperature of the one or more energy terminals to between 0°C and 48°C, more preferably between 5°C and 40°C, and most preferably between 10°C and 35°C.

[0036] Preferably, the method comprises modulating the cycle frequency and / or intensity of the thermal energy.

[0037] Preferably, the method includes varying the rate of temperature change during at least one cooling phase and / or between different cooling phases.

[0038] Preferably, the method includes delivering thermal energy in pulses during at least a portion of at least one cooling phase.

[0039] Preferably, the method comprises cycling thermal energy between successive heating and cooling phases at a frequency of two or more phases per hour, more preferably two or more phases per 10 minutes, and most preferably two or more phases per 3 minutes.

[0040] Preferably, the method comprises applying thermal energy to the area of ​​or adjacent to one or more lacrimal glands or the supraorbital foramen.

[0041] Preferably, the method includes providing data to the controller from one or more temperature sensors located at or adjacent to the one or more energy terminals.

[0042] Preferably, the method includes electrically and / or physically manipulating the eyelid.

[0043] The term "energy" as used herein is intended to mean primarily thermal energy or temperature change, but also mechanical energy such as vibration or massage, acoustic energy, electrical energy that may be modulated in current, voltage, and / or frequency, electromagnetic energy such as gamma rays, x-rays, ultraviolet light, visible light, microwaves, radio waves, and infrared light, chemical energy, or a combination of two or more of the above energies.

[0044] As used herein, the term "thermally responsive area" is intended to mean any target area on or around the human head, preferably around the face, and most preferably the orbital area surrounding and including the eye, hereafter extended orbital area, where application of energy, e.g. thermal energy, to said area results in a physiological response in the form of involuntary activation of tear production in response to stimulation of cells and / or glands in said area.

[0045] As used herein, the term "non-invasive" is intended to mean the non-surgical and potentially non-contact delivery of energy, such as thermal energy, to a target area of ​​the human head, most preferably the skin in the orbital region of the face, and may take the form of indirect cooling of the target area, for example, via an intermediate heat transfer medium.

[0046] The term "power source" as used herein is intended to mean a means for receiving power from an external source, which may be a local power source, such as a battery, that may be removably connected to the device, or alternatively, may be selectively connected to the tear stimulation device, for example by means of a wired or wireless connection.

[0047] The term "energy terminal" as used herein is intended to mean one or more skin-contacting areas or elements of the device that, when the device is worn on the user's head, contact a temperature-responsive area of ​​the user's face and are operable to change the temperature of that area by thermal conduction, and may be defined, for example, by a portion of a sidewall or surface of the housing of the device, or by one or more separate elements provided on or around the housing.

[0048] The present invention will now be described with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0049] [Figure 1] 1 shows a pictorial representation of the human eye. [Diagram 2] 1 shows a schematic cross-sectional side view of the human eye. [Diagram 3] 1 shows a front view of a human head depicting large thermally responsive areas. [Figure 4] 4 shows a profile view of the human head shown in FIG. [Diagram 5] 1 shows a schematic side view of a tear stimulation device according to a first embodiment of the invention adapted for use on a human head; [Figure 6] FIG. 6 shows a front view of the arrangement of FIG. 5. [Figure 7] 7 shows the thermal activation areas of the tear stimulation device of FIGS. 5 and 6. [Figure 8] 2 shows a schematic side view of a tear stimulation device according to a second embodiment of the present invention adapted for use on a human head. [Figure 9] FIG. 9 shows a front view of the arrangement of FIG. 8. [Figure 10] 10 shows the thermal activation areas of the tear stimulation device of FIGS. 8 and 9. [Figure 11] FIG. 2 shows a schematic side view of a tear stimulation device according to a third embodiment of the present invention adapted for use on a human head. [Figure 12] FIG. 12 shows a front view of the arrangement of FIG. [Figure 13] 13 shows the thermal activation areas of the tear stimulation device of FIGS. 11 and 12. [Figure 14] 1 shows a profile of a human head depicting specific thermally responsive areas. [Figure 15] FIG. 15 shows a front view of the human head shown in FIG. [Figure 16] FIG. 13 shows a schematic side view of a tear stimulation device according to a fourth embodiment of the present invention adapted for use on a human head. [Figure 17] FIG. 17 shows a front view of the arrangement of FIG. 16. [Figure 18] 18 shows the thermal activation areas of the tear stimulation device of FIGS. 16 and 17. [Figure 19] 1 shows a profile of a human head depicting specific thermally responsive areas. [Figure 20] FIG. 20 shows a front view of the human head shown in FIG. [Figure 21] FIG. 13 shows a schematic side view of a tear stimulation device according to a fifth embodiment of the present invention adapted for use on a human head. [Figure 22] FIG. 22 shows a front view of the arrangement of FIG. 21. [Diagram 23] 23 shows the thermal activation areas of the tear stimulation device of FIGS. 21 and 22. [Figure 24] FIG. 23 shows a front view of the tear stimulation device of FIG. 21 and FIG. 22 in isolation. [Diagram 25] 1 shows a profile of a human head with eyes open, depicting specific thermally responsive areas. [Figure 26] FIG. 26 shows a front view of the human head shown in FIG. 25. [Figure 27] FIG. 25 shows a profile view of the subject with eyes closed. [Figure 28] FIG. 27 shows a front view of FIG. 26 with eyes closed. [Figure 29] FIG. 13 shows a schematic side view of a tear stimulation device according to a sixth embodiment of the present invention adapted for use on a human head. [Diagram 30] FIG. 30 shows a front view of the arrangement of FIG. 29. [Diagram 31] 29 and 30 show the thermal activation areas of the tear stimulation device. [Diagram 32] FIG. 13 shows a schematic side view of a tear stimulation device according to a seventh embodiment of the present invention adapted for use on a human head. [Diagram 33] FIG. 33 shows a front view of the arrangement of FIG. 32. [Diagram 34] 34 shows the thermal activation areas of the tear stimulation device of FIGS. 32 and 33. [Diagram 35] 1 shows a profile of a human head depicting specific thermally responsive areas. [Diagram 36] FIG. 36 shows a front view of the human head shown in FIG. [Figure 37] FIG. 13 shows a schematic side view of a tear stimulation device according to an eighth embodiment of the present invention adapted for use on a human head. [Figure 38] FIG. 38 shows a front view of the arrangement of FIG. 37. [Figure 39] 39 shows the thermal activation areas of the tear stimulation device of FIGS. 37 and 38. [Diagram 40] FIG. 39 shows a front view of the tear stimulation device of FIG. 37 and FIG. 38 in isolation. [Diagram 41] 1 shows a profile of a human head depicting specific thermally responsive areas. [Diagram 42] FIG. 42 shows a front view of the human head shown in FIG. [Diagram 43] FIG. 13 shows a schematic side view of a tear stimulation device according to a ninth embodiment of the present invention adapted for use on a human head. [Diagram 44] FIG. 44 shows a front view of the arrangement of FIG. [Diagram 45] 45 shows the thermal activation areas of the tear stimulation device of FIGS. 43 and 44. [Figure 46] 1 shows a schematic diagram of the working components of a tear stimulation device according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] Referring now to the accompanying drawings, Figures 1 and 2 show component parts of the human eye A, illustrating a number of cells and glands which, as discussed above, may define part of the thermoreceptor pathway involved in the production of involuntary tears. Figure 1 shows the Kraus gland B, Wolfring gland C, lacrimal gland D, goblet cells E, Popov gland F, and meibomian gland G. Figure 2 shows the cornea H and meibomian gland G.

[0051] As will be described in more detail below, it has been discovered that the controlled application of thermal energy to a thermally responsive region R of the human head, as shown diagrammatically in Figures 3 and 4, can be utilized to cause or increase the involuntary production of tears to provide necessary lubrication to the eyes. This has application to individuals suffering from a variety of conditions that cause a reduction or lack of tear production, particularly during sleep, and can be used to treat such conditions. The type and format of thermal energy delivered to the thermally responsive region R may be varied, such as delivered during a period of time and / or modulated in frequency of application, intensity, duration of application, cycles of heating and cooling, rate of temperature change, etc., and may be delivered simultaneously, sequentially, or otherwise to one or more specific sites within region R, as will be described in more detail below. Thermal energy may be delivered while the user is awake or asleep, with eyes open or closed, although the present invention is particularly intended to enable energy delivery during sleep with the eyes closed.

[0052] 5-7, there is shown a first embodiment of a tear stimulation device according to the present invention, generally designated 10, preferably provided in the form of a headband formed, for example, at least in part, from a stretchy or elastic and flexible material so as to be self-retaining and comfortable to wear. Thus, although the user is shown with their eyes open, the device 10 can be worn while sleeping. The device 10 may be held in the desired position by other means, for example, microneedles, adhesives, suction pads, Velcro, magnets, etc. The device 10 is preferably adjustable to different head sizes, i.e., stretchy, malleable, or adjustable in size via any suitable means (not shown). The device 10 may use ears, nose, hairline, skin texture, or bone structure to hold it in place. The device 10 in the exemplary embodiment shown in FIGS. 5 and 6 is shaped and dimensioned to be located on the brow line adjacent the orbital area, but of course may be any other suitable shape, as detailed by further embodiments described below.

[0053] The device 10 is arranged to deliver thermal energy to a target area within the thermal response region R shown in Figures 3 and 4, and in particular to heat and cool a target area around the eyebrow line. The device 10 is preferably, but not exclusively, arranged to apply thermal energy at the supraorbital foramen toward the ear to cover the path from the lacrimal gland (starting at the orbit, i.e., the inside of the iris when the eye is looking straight ahead, and extending 30 mm therefrom). In particular, the device 10 is arranged to be positioned over the lacrimal gland (location shown in Figure 1) on at least one eye, and preferably both eyes, to apply thermal energy to the area of ​​skin over and / or adjacent to the lacrimal gland, which has been found to be the most effective thermal response area in stimulating tear production. The active cooling area or energy terminal(s) of the device 10 are shown in Figure 7. It will be understood that this is an exemplary heating and cooling area that may be in any other suitable form, for example, multiple individual heating and / or cooling areas. Additional and / or alternative target regions are disclosed in subsequent embodiments described below. It should also be understood that while this exemplary embodiment utilizes thermal energy in the form of sequential heating and cooling as the only form of energy delivered to the target region, one or more additional forms of energy may be delivered. Thus, any reference to heating, cooling or thermal energy should be understood to be inclusive.

[0054] While FIG. 46 shows a schematic diagram of one exemplary combination of hardware components that device 10 may comprise, it will be understood from the following description of the operation of device 10 that this is a non-limiting example and that there are many alternative components (not shown) and combinations that may be utilized to achieve the required operational functionality. In the illustrated embodiment, all of the components shown generally in FIG. 46 are fully contained within the headband of device 10, however, it is also envisioned that one or more components, e.g., a power source in the form of a battery, may be located external to device 10 and / or removably attached thereto. Additionally, while stimulation device 10 is shown as a dedicated or fully contained device 10, it is also envisioned that stimulation device 10 of the present invention may be provided in other form factors, e.g., fitted to and / or supported by other articles worn by a user, such as glasses, wigs, jewelry, hats, face masks, or other articles worn on or about the head.

[0055] The device 10 of this exemplary embodiment comprises a housing 12 including a controller 14 programmed with control algorithms to provide the device 10 with the capability of autonomous operation. The device 10 further comprises a power source in the form of a battery 16 and a battery management module 18 for providing power to the controller 14. It is envisioned that the battery 16 can be replaced or augmented by energy recovered from spent energy, whether thermal, dynamic or otherwise. The controller 14 operates at least one energy terminal comprising at least one Peltier element 20 and preferably an energy transfer interface 22, which may be provided in various forms as described below. In practice, the device 10 preferably includes at least one pair of Peltier elements 20 for stimulating a thermally responsive area on each eye. A Peltier driver 22 is included to operate each Peltier element 20. The energy transfer interface 22 may include or be located adjacent to a skin contact surface of a headband, for example, to facilitate heating and cooling of the thermally responsive area. The energy transfer interface 22 may comprise one or more energy transfer media, such as a solid, a liquid such as a gel, and / or a gas such as air, to achieve a controlled and targeted delivery of thermal energy from the Peltier element 20. A gas interface may enhance activation of mechanoreceptors, thermoreceptors, and other nerves in the skin in the targeted area, as they are more sensitive in the absence of a solid / liquid interface in the skin. The controller 14 is operable to generate and apply energy at a controlled rate and / or physical movement to generate natural tears by activation of appropriate receptors in the sensory nerves of the eye and orbital region. Modulation of this energy results in repeated generation of tears in a controlled manner. This provides a naturally lubricated and nutritious environment that allows the ocular surface to heal, particularly during sleep, and generally throughout the night.

[0056] Thus, the controller 14 is preferably adapted to operate the various components, in particular the Peltier element(s) 20, autonomously, thereby allowing the device 10 to be used during periods of use, in particular during sleep, without the need for any input by the user. Thus, algorithms running on the controller 14 are operable to utilize relevant data as inputs and provide appropriate control outputs to the respective components of the device 10 in order to cause the device 10 to perform the desired operation. The algorithms are operable to incorporate feedback control, whereby the operation of the device 10 is adapted to various external parameters, as will be described below, in particular providing temperature feedback control. Of course, it should be understood that user control of the device 10 is possible and may be achieved locally, for example via a smartphone S, via a wired or wireless connection such as Bluetooth™, Near Field Communication (NFC), or the like, or remotely via the cloud C. This connection also allows medical professionals or the like to remotely access or monitor data relating to the operation of the device 10 and the user's condition, which allows the medical professionals to monitor the patient and / or modify treatment programs based on said feedback.

[0057] The heat transfer medium associated with the energy transfer interface 22 defining the thermally active area of ​​the device 10 may be contained within a suitable housing (not shown), such as a fluid impermeable reservoir, which may be captured between the layers of material forming the headband. Of course, the energy terminals may include alternative or additional means for generating and delivering energy to the Peltier elements 20, which may be operable to deliver, for example, mechanical, electromagnetic, chemical energy, etc., and in each case the energy transfer interface 22 may be appropriately selected or omitted in certain cases. The energy transfer interface 22 may take the form of, for example, an optical waveguide (not shown) for directing light to the target area. The energy transfer interface 22 may be placed in direct contact with the target area or not, and may be operable to deliver energy to the target area, for example over a relatively short distance. However, when the device 10 is applied to the face or head of a user, it is preferred that the Peltier elements 20 are placed as close as possible to the skin in the thermally responsive area. In an exemplary arrangement, the skin-contacting material of device 10 covering the Peltier elements 20 has a thermal conductivity of 429 W / mK or greater and a thickness of 1 mm or less, and preferably conforms to or complements the shape of the housing 12 while being in intimate contact with the adjacent surfaces of the Peltier cell(s) 20 to maximize heat transfer. Examples of suitable materials are silver and alumina, although any other alternatives that are similarly biocompatible, particularly with orbital skin, may be employed.

[0058] The device 10 further comprises a temperature sensor 24, which is operable to provide information regarding the temperature of the Peltier element 20 and / or the energy transfer interface 22 and / or the ambient temperature of the environment or the user's skin to the algorithm executed in the controller 14. The temperature sensor 24 is preferably arranged to monitor the temperature of both the "heating" and "cooling" sides of the Peltier element 20, and may comprise, for example, two dedicated temperature sensors for this purpose. The temperature sensor 24 is preferably arranged as close as possible to the Peltier element 20 in order to reduce undershoots and / or overshoots of the required temperature applied by the Peltier element 20. An optional indicator such as an LED 26 allows a status signal or other basic information regarding the device 10 to be provided to the user. The device 10 also comprises a communication module 28, which is preferably capable of wireless communication in order to allow the device 10 to be connected, preferably the controller, from an external interface, such as, for example, a smartphone S. A charging station 30 is also shown, which does not form part of the device 10, but may be fitted to the device 10 so that the battery 16 can be recharged in a known manner. Charging may be accomplished wirelessly to avoid the requirement for an external power socket in device 10.

[0059] The device 10 may further comprise one or more additional sensors (not shown) operable to provide information regarding one or more physical and / or environmental conditions, such as local body temperature, tear gland activity, heart rate, hormone levels, air temperature and / or humidity, movement, orientation, sleep cycles, one or more external sources of information, etc., which may be in communication with the controller 14 to enable autonomous feedback control of the device 10. For example, the device 10 may comprise one or more heat sinks for dissipating thermal energy generated, for example, from the Peltier element 20, and the device 10 may potentially be operable to direct this thermal energy to the most appropriate heat sink depending on the orientation of the device 10 as determined by the position of the user's head. For example, if a user is lying on one side of their head against a pillow or the like, it may not be appropriate or effective to utilize a heat sink on that side of the device 10, whereby the controller 14 may be operable to select a heat sink on the opposite exposed side of the device 10 from which heat can more easily escape. Of course, additional decision-making functionality may be provided and controlled by algorithms executed in the controller 14.

[0060] The tear stimulation device 10 of the present invention may also include one or more systems (not shown) for holding the eyelids closed, particularly to prevent evaporation of newly stimulated tears, to protect against contact or other irritants, to reduce incident light, and / or to maintain a consistent temperature around the eye. This may also be beneficial in treating nocturnal lagophthalmos, which means that a dysfunctional eyelid does not close completely during sleep.

[0061] The device 10 may also include one or more systems (not shown) for massaging the eyelid to prevent the eyelid from sticking to the eye (cornea) along the inner surface of the eyelid when lubrication between the surfaces is low. The device 10 may further include one or more systems (not shown) for holding the eyelid partially open to allow access for energy modulation to the cornea, which may take the form of, for example, electrical stimulation to the eye area.

[0062] The device 10 may be adapted to manipulate the eyelids by either mechanical or electrical means, for example, to prevent eyelid sticking when lack of lubrication is an issue and to facilitate improved energy transfer to the cornea / ocular surface. Eyelid manipulation may also be used to move freshly stimulated tears across the ocular surface or to keep the eyelids closed to reduce evaporation of stimulated tears. Mechanical means for moving the eyelids may include, for example, a material in contact with the outer eyelid, and may be moved by suitable mechanical and / or electrical means (not shown), such as one or more servos, piezoelectric actuators, etc. Electrical means for manipulating the eyelids may also be achieved by electrical stimulation of the nerves involved in contracting and relaxing the eyelid muscles.

[0063] In use, a user applies the device 10 as shown in FIGS. 5 and 6 such that the active heating and cooling regions of the device 10 as shown in FIG. 7 are correctly positioned. The device 10 may be manually activated or may trigger activation of the device 10 by utilizing data from one or more sensors (not shown) to detect that the user is wearing the device 10 and / or sleeping. Alternatively, the device 10 may be programmed to operate for a pre-set time or for a pre-set period of time. Once activated, the device 10 non-invasively delivers thermal energy to the target area and the controller 14 is operable to modulate the energy to cause the involuntary activation of tear production. Energy modulation may affect tear production by affecting neural pathways to secrete tears at different locations such as thermoreceptors, mechanoreceptors, polymodal receptors, nerves or glands. These receptors are located in various areas of the target area and the device 10, particularly the thermally active regions as shown in FIG. 7, may be configured to apply energy to specific receptors or groups of receptors. For example, the device 10 may target receptors in the orbital region, particularly the lacrimal gland, the skin of the eyelids, the skin and inner mucosa of the nose, and the skin on or around the cornea with the eyelids open or closed. Thus, the target regions may be the eyebrows, forehead, nasal region, orbital region, temples adjacent to the orbital region, the outer and / or inner nose, and cheekbones, or any combination of the above. The device 10 is preferably operable to generate continuous thermal energy cycles for a specified period of time, as described in more detail below. The application of additional forms of energy, whether constant or modulated, may assist the action of tear secretion by influencing neural pathways to secrete tears at different locations, such as thermoreceptors, mechanoreceptors, polymodal receptors, the nerves themselves, or glands.

[0064] The device 10, and in particular the controller 14, is operable to modulate or alter the energy profile to deliver thermal energy to the target area and, in use, stimulate the necessary cells and / or glands to affect tear production. For example, the controller 14 may be programmed to modulate the temperature of the Peltier element 20 to modulate the temperature at the thermally responsive target site. However, the modulation parameters may vary depending, for example, on the form of energy being applied, physiological conditions, sleep states, etc., and may be changed autonomously based on feedback from one or more sensors (not shown). If mechanical energy, such as massage, is being applied in combination with the thermal energy, the frequency and intensity of the massage may be modulated. If electromagnetic energy is being applied, the frequency, wavelength and / or intensity may be changed. The length of time that energy is applied may also be modulated, as may the length of the intervening periods during which no energy is applied.

[0065] The device 10 may operate a hierarchical control scheme in which at higher levels are included programs covering the entire period of use, e.g. overnight or during sleep. A program is thus the complete period during which the device 10 is intended to be used in one treatment session. All programs relate to waking times as well as sleeping times. For example, the device 10 may be used purely to generate lacrimation during sleep or wakefulness, hereinafter referred to as the operation of a lacrimation program, but may also be used to promote sleep, hereinafter referred to as the operation of a sleep promotion program. A sleep promotion program may operate with or without lacrimation, e.g. without stimulating lacrimation or to simply relax the wearer by applying heat, massage, etc. before stimulating lacrimation. However, it is envisaged that the main use of the device 10 is only to generate lacrimation during the night or during sleep. Each program may include multiple phases, while each phase may define multiple "unit operations". Each operational unit may include multiple individual cycles, as explained below. Algorithms executing on the controller 14 are programmed to implement an appropriate control scheme for each program and to incorporate feedback control based on data received from one or more sensors or other sources.

[0066] At the lowest level of the hierarchical control scheme, there are a number of different thermal energy cycles that may be implemented by the device 10. The different defined energy levels and rates of energy change within a cycle may be influenced by factors such as the energy of the body at rest or the energy input from the device 10. An energy cycle may consist of bringing the thermal energy to a defined start level at a defined rate, then changing the energy at a defined rate, holding at the new energy level for a defined period of time, and changing at a defined rate to a defined end energy level. The rate of energy change may be of various profiles, including but not limited to sinusoidal, linear, and stepped profiles. An energy cycle may also include a hold cycle, which may consist of an energy source controlled by a cycle that is held at a defined energy level for a defined period of time, and / or an energy source that is controlled by a cycle that is turned off for a defined period of time.

[0067] Particularly and surprisingly, it has been found that the cyclic application of thermal energy to the thermoresponsive region in successive heating and cooling phases is particularly effective in stimulating tear production, and in particular that an increase in the rate of temperature change during the cooling phase has a significant and surprising effect on tear stimulation. In particular, it has been found that a rate of temperature change during the cooling phase at the thermoresponsive target site of 0.01° C. / sec to 43° C. / sec, more preferably 3° C. / sec to 25° C. / sec, and most preferably 5° C. / sec to 20° C. / sec, leads to significant tear production. This rapid cooling of the thermoreceptors stimulates them to a surprising level to cause significant and complete tear stimulation. Once the cooling phase is complete, the device 10, under the operation of the controller 14, utilizes the Peltier cell(s) 20 to heat the thermoresponsive region. This has the effect of returning the stimulated thermoreceptors to a precise baseline temperature at a specific rate in order to reset the sensitivity of the thermoreceptors, particularly with respect to the immediately following cooling phase performed by the device 10. In addition to returning the thermoreceptors to this baseline temperature, the heating phase can act to clear blocked meibomian glands by heating trapped meibomian secretions and causing them to flow and clear the glands, further improving overall tear quality. Additionally, the increased rate of temperature change during the cooling phase activates the so-called "blink response" which enhances the action of the device 10 in achieving tear stimulation, both by uniformly coating the cornea with tear fluid and by cooling the cornea through direct contact with the eyelid, which is rapidly cooled by the device 10. In one study, blinking rate more than doubled with application of the device 10, from an average of 20 blinks per minute to an average of 45 blinks per minute, when a cooling rate of 5°C / sec was used, as measured using video analysis.

[0068] By precisely controlling the rate of temperature change and the absolute temperature applied, periodic input is provided to the thermoreceptors to effectively retrain their response to the ambient temperatures experienced during normal biological function. Thus, device 10 is operable to repair or retrain damaged thermoreceptors.

[0069] The effectiveness of the tear stimulation device 10 was evaluated using Myah™, supplied by Topcon Healthcare, an eye testing and screening device used in the field of optometry, which provides data on multiple indicators of tear stimulation, particularly tear meniscus height (TMH).

[0070] In studies with Myah™, the following study protocol was employed.

[0071] A. Baseline tear meniscus height (TMH) measurements are taken with the subject in a seated position, with the chin placed on the Myah™ chin rest, the forehead placed against the Myah forehead strap and looking straight into the Myah™ Device.

[0072] B. The Myah™ operator selects the "TMH" measurement option from the on-screen menu. The operator then adjusts the Myah™ while the subject is still, to focus the Myah™ crosshairs on the tear meniscus (the lower meniscus is measured at the bottom of the eye).

[0073] C. Precision move the Myah™ joystick to focus on the TMH of the eye under test.

[0074] D. Once the operator is focused on the TMH, a button on the Myah™ joystick is pressed and an image of the TMH is taken.

[0075] E. The image is then analyzed using the Myah™ interface. The image is optimized by the Myah™ software to highlight the tear meniscus. The upper and lower edges of the TMH are identified on the magnified image and Myah™ calculates the TMH.

[0076] F. The subject then remains in a seated position, removes his / her head from the Myah™, and the device 10 of the present invention is placed over the temperature responsive area of ​​the orbital region and the device 10 executes the predetermined temperature algorithm.

[0077] G. Once the predetermined temperature algorithm is completed, the subject removes the device 10 and TMH is measured again according to steps A-E above.

[0078] An exemplary thermal energy cycle of the device 10 tested using Myah™ involved bringing the thermally active area of ​​the device 10, i.e., the area in direct heat transfer with the Peltier cell(s) 20, from 37° C. to 20° C. at a defined rate of change of 6° C. / sec. This rate of temperature change during the cooling phase showed an increase in TMH of 0.21 mm and 0.15 mm across the two tests.

[0079] Another example of a temperature cycle or sequence performed by the apparatus 10 and evaluated using Myah™ included a temperature ramp from 35° C. to 25° C. for 2.5 seconds at a ramp rate of 4° C. / sec, followed by a ramp from 25° C. to 23° C. for 10 seconds at a ramp rate of 0.2° C. / sec, followed by a ramp to 35° C. at 2° C. / sec, repeated two more times, which resulted in an increase in TMH of 0.16 mm.

[0080] A further sequence tested included a temperature ramp from 35°C to 26°C for 1.5 seconds at a ramp rate of 6°C / s, followed by a ramp from 26°C to 23°C for 9 seconds at a ramp rate of 0.3°C / s, followed by a hold at 23°C for 18 seconds, followed by a heating phase to 35°C at a rate of 2.5°C / s for 2 seconds, resulting in TMH increases of 0.12mm, 0.18mm and 0.19mm in three trials.

[0081] Another sequence tested employed a temperature ramp from 35°C to 25°C for 5 seconds at a ramp rate of 2°C / s, then a ramp from 25°C to 20°C for 5 seconds at a ramp rate of 1°C / s, then a ramp to 35°C for 5 seconds at a rate of 1°C / s, this cycle repeated 9 more times resulting in an increase in THM of 0.25 mm.

[0082] The above tests were conducted in locations having environmental temperatures ranging from 16°C to 19°C, and device 10 was positioned on the skin of the test participant to achieve a predefined temperature change at a specified rate.

[0083] It will be appreciated that the above tests are exemplary and that numerous alternative cycles, sequences, temperature and rate changes may be employed to achieve the desired results or treat a particular case. For example, to control reflex tear lacrimation followed by basal tear production, a sequence may include a heating phase of heating to 35° C. at a rate of 1° C. / sec and holding for 120 seconds. Then a cooling phase of cooling to 10° C. at a rate of 25° C. / sec and holding for 20 seconds. Then a further heating phase of heating to 35° C. at a rate of 2° C. / sec and holding for 60 seconds. Then a cooling phase of cooling to 20° C. at a rate of 15° C. / sec and holding for 20 seconds. Then heating to 35° C. at a rate of 2° C. / sec and holding for 60 seconds. Then ...

[0084] At the next level of the control scheme are stages, where the programs for tear production and for sleep promotion may consist of various stages, for example a first stage for relaxation, during which the user has time to relax physically and / or mentally. A second or pre-sleep stage is the period immediately prior to sleep time. A third or sleep stage defines a period intended to be devoted solely to sleep, and a fourth or post-sleep stage defines immediately after waking up.

[0085] A stage is composed of one or more of the unit operations. Each stage can have multiple unit operations in any order. The unit operation of lacrimation may be different from the unit operation of sleep facilitation. The unit operation for lacrimation may be multiple and continuous, such as mimicking blinking. The unit operation of lacrimation during sleep facilitation may be continuous, such as mimicking closed eye tears, which is defined as lubrication of the eyes during extended periods of eye closure, especially during nighttime sleep, but also possible while awake. The unit operation may define flushing to produce focused, exaggerated, and continuous tears, mimicking yawning, which may be achieved by more frequent and intense energy fluctuations. A further unit operation may be defined as a maintenance unit operation to maintain the consistency of the meibum of the meibomian glands of the eye and the consistency of all the oils of all the glands of the skin, which may be affected by a decrease in temperature of the previous two or any "unit operation". A unit operation is a pattern produced by one or more simultaneous cycles or by an energy source at different locations within a target zone at different frequency intervals. Examples are energy waves or gradient patterns across the thermally active region of device 10, such as horizontal, vertical and / or diagonal stretches, concentric circles, multiple alternating pulses, etc., generated in the thermally active region of device 10.

[0086] As mentioned above, the device 10 may have sensors (not shown) that can be used to measure markers related to sleep, eyes, brain activity, REM sleep, sleep patterns, etc. This data can be used to inform programs for tear production and sleep / relaxation promotion. The data can be used to improve understanding of dry eye and sleep, including weather aspects, amount of exercise, body hydration, medication use, food / supplements, and other influences such as contact lenses, hormones, reading time, driving time, screen time, recording of signs and symptoms, etc. This information can be provided to a medical professional or the like for appropriate review.

[0087] The number of cycles and other variables described above may be controlled by feedback from sensors (not shown) or other sources or data points (e.g., based on temperature, tear production, wetness or other changes in indicators, daily activity, computer usage, exercise, amount of sleep the previous night, sleep, or environmental conditions for the day). The device 10 may operate in a closed loop or semi-closed loop mode, operable to directly or indirectly detect the level of tear production and adjust the control system in real time or on a tracking basis.

[0088] The device 10 shown in Figures 5-13 was tested on a sample group of users to demonstrate efficacy and used the exemplary control scheme. The eyes were closed for testing. A set point of 20°C was applied to the energy terminals for 20 seconds. The tear meniscus acts as a reservoir and provides tear fluid to the precorneal tear film. The majority of the tear fluid is contained within the meniscus, which is formed by the tear fluid located at the junction of the bulbar conjunctiva and the upper and lower eyelid margins. A tear meniscus height of less than 0.25 mm is indicative of dry eye. Test results showed a 68% increase in tear meniscus height after use of the device 10.

[0089] A tear stimulation device according to the present invention may be provided in a number of form factors and can be designed to suit, for example, a particular application, user settings, control schemes, target areas to which heat and any other energy is to be delivered, in addition to a variety of other factors. Figures 5-13 show an embodiment of a device 10 that is a variation of a headband form factor and is designed to apply thermal energy to a thermally responsive target area along the eyebrow adjacent the orbital region, and may be used during sleep or while the user is awake, as device 10 does not cover the eyes.

[0090] Figures 14 and 15 show an expanded target area including the eyebrows and forehead, and Figures 16-18 show generally an embodiment of device 10 designed to deliver thermal energy to this target area, with Figure 18 highlighting the thermally active area of ​​device 10. It should be understood that the thermally active area may also include the delivery of mechanical or other forms of energy, and the term "thermally active area" should be interpreted throughout to potentially encompass these alternative forms of energy. As with the previous embodiment, this version of device 10 may be used during sleep as well as while the user is awake.

[0091] An exemplary control scheme for these devices 10 may include cooling to achieve a localized temperature of 0.01 to 43°C, more preferably 37°C to 20°C, for comfort and tolerability in the orbital region. The device 10 may include a thermal energy interface in the form of a heat transfer medium of silicon and / or air that defines a thermally active region. A temperature drop from 37°C to 20°C at a rate of change of 6°C / sec provides the temperature drop required to activate the cold thermoreceptors in the eyelid skin. The amount of temperature drop may be varied (to prevent the thermoreceptors from becoming habituated to the stimulus and becoming unresponsive). Just as the frequency of the cycles may vary, for example, from 1 to 60 cycles per minute, the duration of the cycles may also vary in length. The duration of a complete cycle may be of any suitable length, or may occur less frequently, i.e., once per hour or less. Also, a complete cycle may be of any suitable duration, for example, less than 1 second.

[0092] 19 and 20 show a target area relative to the nose, and FIGS. 21-24 show an alternative embodiment of a tear stimulation device according to the invention for applying energy to this target area, generally designated 110. In this alternative embodiment, like components are given like reference numerals and perform like functions unless otherwise stated. The device 110 is provided in the form of a frame attached to the temples, similar to a conventional pair of eyeglasses without lenses, and the thermally active area is defined by a bridge 40 and a pair of contact pads in the form of nose pads 42 depending from the bridge 40. The hardware components of the device 110 may be provided in a housing 112 formed integrally with the frame, but could equally be located in an externally located housing fixed to the frame, or in a housing located remote from the frame and suitably connected, with only the energy terminals and the energy transfer interface being located on or within the frame, the bridge 40 and the nose pads 42 defining the energy transfer interface. To achieve the desired energy transfer profile, any suitable energy transfer medium may be provided on the bridge 40 and nose pads 42, such as a highly thermally conductive material to maximize thermal energy transfer from the device 110 to the target area. A suitable material is thermally conductive silicone, or silicone encapsulating a thermally conductive element. The device 110 is designed to be used with the eyes open or closed.

[0093] 25-28 show further target areas including the eyelids when open or closed, as eyelid thermoreceptors may be activated when the eyelids are open and when closed as shown in FIGS. 27 and 28. FIGS. 29-31 show alternative arrangements of the headband form factor device 10, which is shaped and dimensioned to occlude the eyes when worn, and is therefore intended to be worn with the eyes fully closed, for example, but not limited to, during sleep. FIG. 31 highlights the thermally active area of ​​the device 10, which is provided as two separate sections shaped and dimensioned to cover the eyes to apply energy to the eyelids and effectively define a contact pad for the eyes. Additional energy delivery zones may of course be provided in the thermally active area of ​​the device 10. The housing 12 includes hardware components of the device 10 other than the energy terminals and energy transfer interface that define the thermally active area.

[0094] The device 10 may be controlled to affect cooling from 0°C to 43°C. For tear secretion, the preferred temperature drop range is 40°C to 0°C for 16.5 seconds. For meibum maintenance, the preferred temperature range is 38.5°C to 43°C, although higher temperatures have been found to be beneficial. For oil glands in other skin sites other than the eyelid, the preferred temperature range is similar to that of the meibum. The amount of temperature drop can be varied (to prevent thermoreceptors from becoming habituated to the stimulus and becoming unresponsive). The rate of temperature drop can be 0.01°C / sec to 43°C / sec, more preferably 3°C / sec to 25°C / sec, and most preferably 5°C / sec to 20°C / sec. The rate of temperature drop can be varied (to prevent thermoreceptors from becoming habituated to the stimulus and becoming unresponsive). This variation may be within one cooling phase and / or between separate cooling phases within one cycle. The duration of the cycle may vary in length, such as 1 to 60 cycles per minute. The duration of one complete cycle may also occur less frequently, i.e., once an hour or less. A complete cycle may be less than one second.

[0095] 32-34 show a further alternative embodiment of a tear stimulation device according to the present invention, generally designated as 210. In this alternative embodiment, like components are given like reference numbers and perform like functions unless otherwise stated. The device 210 is provided in the form of a pair of nose-mounted contact pads 244 connected by a bridge 240. The hardware components of the device 210 may be provided within the bridge 240 and / or the pads 244, but may equally be located in an externally located housing or a housing located away from and appropriately connected to the pads 244, with only the energy terminals and energy transfer interface located on the eye pads 244 to define the energy transfer interface. To achieve the desired energy transfer profile, the eye pads 244 may be provided with any suitable energy transfer medium, such as, for example, a highly thermally conductive gel that facilitates thermal energy transfer and allows the pads 244 to adhere to the eyelids and surrounding skin. The device 210 is intended for use with the eyes closed. However, the pad 244 may be transparent so that it can be used with the eyes open to allow observation through the pad 244. The pad 244 may be formed with a transparent outer barrier or envelope that contains a transparent energy transmission medium, such as a clear gel. It will be appreciated that such an arrangement may be applied to the other embodiments described herein.

[0096] In Figures 35 and 36 a further target area is shown between the eyes and the temples on either side of the head. Figures 37-40 show an alternative embodiment of a tear stimulation device according to the invention, generally designated 310, adapted to deliver energy to this target area. In this alternative embodiment like components are given like reference numerals and perform like functions unless otherwise stated. The device 310 is provided in the form of a frame extending around the sides and rear of the head, the thermally active area being defined by a pair of contact pads in the form of temple pads 342.

[0097] Figures 41 and 42 show further target areas around the cheeks. Figures 43-45 show an alternative embodiment of a tear stimulation device according to the present invention, generally designated 410. In this alternative embodiment like components are given like reference numbers and perform like functions unless otherwise stated. The device 410 is provided in the form of a frame which extends around the sides and back of the head and across the bridge of the nose, with the thermally active area being defined by a pair of contact pads in the form of cheek pads 442.

[0098] For each of the above embodiments, it will be understood that the description of the components of the device 10 as shown generally in FIG. 46 applies in addition to the various modes of operation discussed above.

[0099] Thus, the tear stimulator device 10;110;210;310;410 of the present invention provides an effective means of delivering thermal energy at a controlled rate to stimulate natural tear production by activating the sensory nerves of the eye and thermoreceptors in the extended orbital region, as shown in Figures 3 and 4. By modulating the energy, particularly by means of controlling the rate of temperature change, a naturally lubricated and nourishing environment is established in which tears can be produced repeatedly in a controlled manner to heal the ocular surface, particularly during sleep.

Claims

1. A tear stimulation device comprising a housing, a controller, a power supply, and one or more energy terminals disposed around the housing for transferring thermal energy between the face's heat response area, such as inducing or increasing the unconscious activation of tear production. The controller is arranged to circulate the temperature of the one or more energy terminals to deliver continuous heating and cooling phases. The controller is arranged to lower the temperature of the one or more energy terminals at a rate of 0.01 °C / second to 43 °C / second, more preferably 3 °C / second to 25 °C / second, and most preferably 5 °C / second to 20 °C / second, and is arranged in at least one of the cooling phases. The tear stimulation device.

2. The controller is arranged to maintain a constant temperature at the one or more energy terminals during one or more of the heating and / or cooling phases over a period of 1 second to 6000 seconds, more preferably 1 second to 120 seconds, and most preferably 1 second to 60 seconds. The tear stimulation device according to claim 1.

3. The controller is arranged to set the temperature at the one or more energy terminals at 0 °C to 48 °C, more preferably 5 °C to 40 °C, and most preferably 10 °C to 35 °C. The tear stimulation device according to claim 1 or 2.

4. The controller is arranged to modulate the cycle frequency and / or intensity of the thermal energy. The tear stimulation device according to claim 1.

5. The controller is arranged to cause a pulsed temperature change at the one or more energy terminals during at least a part of at least one cooling phase. The tear stimulation device according to claim 1.

6. The controller is arranged to change the rate of temperature change during and / or between the at least one cooling phase and / or different cooling phases. The tear stimulation device according to claim 1.

7. The controller is arranged to circulate the thermal energy between continuous heating and cooling phases at a frequency of two or more phases per hour, more preferably two or more phases per 10 minutes, and most preferably two or more phases per 3 minutes. The tear stimulation device according to claim 1.

8. The one or more energy terminals comprise a thermoelectric cooler. The tear stimulation device according to claim 1.

9. The tear stimulation device according to claim 1, wherein the one or more energy terminals are arranged to apply the thermal energy to an area of one or more lacrimal glands or supraorbital foramina, or an area adjacent thereto.

10. The tear stimulation device according to claim 1, further comprising one or more temperature sensors arranged on or adjacent to the one or more energy terminals.

11. The tear stimulation device according to claim 1, wherein the housing comprises a support operable to removably fix the device to a user or to clothing worn by the user.

12. The tear stimulation device according to claim 1, wherein the support comprises a headband.

13. The tear stimulation device according to claim 1, wherein the one or more energy terminals comprise one or more energy transfer interfaces operable to deliver thermal energy to the temperature-responsive area.

14. A method for inducing or increasing tear stimulation, comprising applying one or more energy terminals to a heat-responsive area of the face and transferring thermal energy between the heat-responsive area via the one or more energy terminals to continuously heat and cool the heat-responsive area, wherein at least one cooling phase reduces the temperature of the one or more energy terminals at a rate of 0.01 °C / second to 43 °C / second, more preferably 3 °C / second to 25 °C / second, and most preferably 5 °C / second to 20 °C / second.

15. The method according to claim 14, comprising maintaining the one or more energy terminals at a constant temperature during one or more of the heating and / or cooling phases for a period of between 1 second and 6000 seconds, more preferably between 1 second and 120 seconds, and most preferably between 1 second and 60 seconds.

16. The method according to claim 14 or 15, comprising setting the temperature of the one or more energy terminals to 0 °C to 48 °C, more preferably 5 °C to 40 °C, and most preferably 10 °C to 35 °C.

17. The method according to claim 14, comprising modulating the cycle frequency and / or intensity of the thermal energy.

18. The method according to claim 14, comprising varying the rate of temperature change during and / or between at least one cooling phase and different cooling phases.

19. The method according to claim 14, comprising delivering the thermal energy in pulses during at least a portion of at least one cooling phase.

20. The method according to claim 14, comprising the step of circulating said thermal energy between successive heating and cooling phases at a frequency of two or more phases per hour, more preferably two or more phases per ten minutes, and most preferably two or more phases per three minutes.

21. The method according to claim 14, comprising applying said thermal energy to the region of one or more lacrimal glands or supraorbital foramina, or a region adjacent thereto.

22. The method according to claim 14, comprising providing data from one or more temperature sensors disposed on or adjacent to said one or more energy terminals to said controller.

23. The method according to claim 14, comprising electrically and / or physically manipulating the eyelids.

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