System and method for treating dry eye disease using radiofrequency

Abstract

A system and method for treating dry eye disease / syndrome of a subject, comprising: a controller and an energy signal generator. Further comprising at least one energy applicator configured receive energy signals from the energy signal generator, and to apply a first energy signal and a second energy signal different from the first energy signal to the periocular region of the subject's eye. Wherein the first energy signal is configured to heat up to a predetermined temperature, Meibomian glands of the eye and the second energy signal is configured to heat up to a predetermined temperature collagen fibers in the eye.

Description

[0001] SYSTEM AND METHOD FOR TREATING DRY EYE DISEASE USING RADIOFREQUENCY

[0002] RELATED APPLICATIONS

[0003] This application is related to US Provisional Application No. 63 / 532,731 filed on August 15, 2023, entitled “DEVICE AND METHOD FOR IMPROVING DRY EYE DISEASE USING RADIOFREQUENCY,” to which application priority is hereby claimed and the contents of which are incorporated herein by reference in its entirety.

[0004] TECHNICAL FIELD

[0005] The present disclosure relates to the medical field. Particularly, but not exclusively, the present disclosure relates to systems and methods for treating dry eye disease.

[0006] BACKGROUND

[0007] Dry eye disease is a common condition causing discomfort and may also lead to inflammation and damage of the eye's ocular surface.

[0008] The Meibomian glands, located in the inner eyelids, are responsible for producing meibum, an oily secretion forming a protective coating over the tear film protecting the eye. Dry eye disease may occur when the Meibomian glands disfunction or become clogged, thereby meibum secretions is reduced or clogged causing a faster evaporation of the tear film. A common type of such clogging is blepharitis, a chronic inflammation of the eyelid margin, which may be caused by pathogens such as bacteria and skin mites (demodex). In addition, blinking is also responsible for spreading nourishing tears and meibum across the eyes. Incomplete blinking, where the lower and upper eye lid do not meet, may lead, or accelerate dry eye syndromes.

[0009] Traditional treatments for dry eye have included eyedrops and topical steroids and ointments. More recently, medical instruments have been introduced that can enhance or even replace the use of such medicaments.

[0010] US Patent Nos. 9,333,370 and 10,085,814, assigned to the assignee of the present disclosure and incorporated herein by reference in their entirety, are directed to dry eye treatments using light energy. For example, light-based treatment such as treatment with IPL (Intense Pulsed Light) has a long-lasting effect and bacteria and skin mites are successfully eliminated, and the inflammation cycle is stopped. IPL may be used to treat the inflammatory

[0011] 1

[0012] SUBSTITUTE SHEET (RULE 26) causes of dry eye, stimulate the eyelid glands, and accelerate healing. The use of a light source is for the purpose of generating heat and causing photo modulation, so as to heat up the area of a meibomian gland, soften the paste-like secretion oil to a more liquid form to enable easy expression of the glands. During treatment, one or more pulses of light may be delivered to patient's eyelids or to the periocular region surrounding the eye. Care should be taken to avoid direct light entry into the cornea, as well as exposure of eyelashes to the energy (to avoid hair loss). In addition, direct illumination of the cornea and other ocular surfaces with IPL should be avoided. IPL treatment usually requires a few sessions (3-5) to get the maximum effect, which can take around a month. During this time, patients continue to suffer from pain and discomfort.

[0013] SUMMARY

[0014] The presently disclosed subject matter provides systems and methods for dry eye disease treatment, by at least improving the eye surface lubrication or by reducing dry eye syndromes in other ways.

[0015] In an exemplary embodiment, the present disclosure discloses a system for treating dry eye disease / syndrome of a subject. The system comprises at least one energy applicator, configured to apply a first energy signal and a second energy signal different from the first energy signal to a target treatment region of a periocular region of a subject’s eye. The periocular region is the area around the subject’s eye, including but not limited to one or both eyelids of the subject’s eye. The combination of the first and second energies is configured to improve different conditions related to the dry eye disease. In some embodiments, the first energy signal is configured to improve the expression or secretion conditions of Meibomian glands of the eye and the second energy signal is configured to improve quality of blinking in the subject’s eye.

[0016] In another exemplary embodiment, the present disclosure discloses a method for treating dry eye disease / syndrome of a subject, the method comprising applying a first energy signal and a second energy signal different from the first energy signal to the periocular region of the subject’s eye; the combination of the first and second energies is configured to improve different conditions related to dry eye disease. In some embodiments, the first energy signal is configured to improve expression or secretion conditions of Meibomian glands of the subject’s eye and the second energy signal is configured to improve quality of blinking in the subject’s eye. In some embodiments, the first and second energy signals are radiofrequency (RF) signals.

[0017] 2

[0018] SUBSTITUTE SHEET (RULE 26) In some embodiments, the first energy signal is of a first frequency or frequency range and the second energy signal is of a second frequency or frequency range higher than the first frequency or frequency range. In some embodiments, the first energy signal has a frequency of about 1 MHz. In some embodiments, the second energy signal has a frequency of about 4 MHz. In some embodiments, the first energy and the second energy signals are configured to treat different depths within the eyelids or near the subject’s eye.

[0019] In some embodiments, the first and / or second energy signal applications utilize a monopolar configuration. Alternatively, or additionally, the first and / or second energy signal utilize a bipolar and / or multipolar configuration. In some embodiments, the second energy signal targets subject’s eyelid skin region in order to improve the blinking quality of the subject’s eye. In some embodiments, the first or second energy signals are aimed at heating the periocular region of the subject’s eye to a temperature between 37° C and 45° C. In another embodiment, the first and second energy signals are aimed at heating the periocular region of the subject’s eyes to about 41° C.

[0020] In some embodiments, the treated area of the subject’s eye extends between the supraorbital foramen and anterior lacrimal crest, along the orbital rim. In some embodiments, the method comprises at least one treatment session comprising applying the first energy signal for a first period and the second energy signal for a second period. The first and second periods may be equal. In one example, each of the first and second periods may be equal to between one to five minutes. In some embodiments, each of the first and second periods may be equal to about three minutes. The method may include a plurality of treatment sessions at predetermined time intervals.

[0021] In some embodiments, the system comprises a handheld probe comprising the at least one energy applicator, the handheld probe being configured for manipulation by a user to apply the treatment to the periocular region of the subject’s eye. The at least one energy applicator may be mounted on a distal end (closer to the treated subject) of the handheld probe. The at least one energy applicator may be mounted on a disposable tip connectable to the distal end of the handheld probe. The handheld probe may include a plurality of energy applicators arranged to provide an optimized treatment to the periocular region of the subject’s eye. In some embodiments, the first and second energy signals may be applied simultaneously.

[0022] In some embodiments, the system comprises an energy signal generator / source for generating the at least one first and at least one second energy signals. The energy signal generator may be located in the handheld probe or outside the handheld probe while being connectable to the at least one energy applicator.

[0023] 3

[0024] SUBSTITUTE SHEET (RULE 26) In some embodiments, the at least one energy applicator is at least one electrode connected to the signal energy generator. The electrode may have a shape adapted to apply the treatment to the periocular region of the subject’s eye. The electrode(s) shape may be flat or curved. The curved electrode may be convex or concave. The electrode may have a size adapted to treat the periocular region of the subject’s eye. The electrode may have a treatment portion having a substantially circular and / or spherical shape with a diameter of between about 5mm to 15mm. In some embodiments, the substantially circular and / or spherical shape has a diameter of 10mm. In some embodiments, the at least one energy applicator is covered with a flexible material, being electrically conductive, to enhance coupling / attachment to the region of the subject’s eye.

[0025] In some embodiments, the system comprises a controller configured and operable for controlling at least one of the energy signal generators and the at least one energy applicator.

[0026] In some embodiments, the system comprises a tissue impedance measurement unit configured to provide a tissue impedance measurement to the controller, enabling fine tuning and personalization of the at least one first and second energy signals to the treated subject. For example, the controller may adjust the frequency or / and intensity of the energy signals.

[0027] In some embodiments, the system comprises a tissue temperature measurement unit configured to provide tissue temperature measurement to the controller, enabling fine tuning and personalization of the at least one first and second energy signals to the treated subject. In some embodiments, the tissue impedance and temperature measurement units are located in a vicinity of the treated region of the subject’s eye, e.g. at least partially mounted on the handheld probe. In some embodiments, the method comprises applying a complementary treatment with an optical energy signal, such as IPL.

[0028] In one aspect of the disclosure there is a system for treating dry eye disease of a subject, comprising: a controller configured to adjust frequency or / and intensity of energy signals; an energy signal generator; at least one energy applicator configured to receive the energy signals from the energy signal generator, to apply a first energy signal and a second energy signal different from the first energy signal to a target treatment region of a periocular region of the subject’s eye, wherein the first energy signal is configured to reach a predetermined target temperature to heat Meibomian glands of the eye and the second energy signal is configured to reach a predetermined target temperature to treat collagen fibers. The system, wherein the energy applicator comprises at least one electrode connected to the energy signal generator, the first and second energy signals are first and second radio frequency (RF) signals, the first RF signal is of a first frequency or frequency range, and the second RF signal is of a second

[0029] 4

[0030] SUBSTITUTE SHEET (RULE 26) frequency or frequency range higher than the first frequency or frequency range. Also, the system, wherein the first RF signal has a frequency of about 1 MHz, the second RF signal has a frequency of about 4 MHz, and both the first and second RF signals are applied to the target treatment region by the at least one electrode.

[0031] In another aspect of the disclosure the system, wherein the first and second RF signal applications utilize at least one of: a monopolar configuration; a bipolar configuration; or a multipolar configuration; the at least one electrode is one electrode configured to apply both the first and second RF signal; the at least one electrode is / are one of; a flat electrode, a curved electrode, a curved convex electrode, or a curved concave electrode. Also, the system is a handheld probe, and the handheld probe comprises the at least one energy applicator configured to be mounted on a distal end of the handheld probe and the handheld probe is further configured for manipulation by a user to apply the treatment to the target treatment region, and wherein the energy signal generator is disposed in the handheld probe or outside the handheld probe.

[0032] In yet another aspect of the disclosure, the system, wherein the controller is configured to apply the at least first energy signal and the at least one second energy signal simultaneously; the second energy signal targets the subject’s eyelid region in order to improve the blinking quality of the subject’s eye; and the at least one energy applicator is covered with a flexible electrically conductive material, thereby enhancing coupling and attachment to the treated target treatment region. The system further comprising a tissue impedance measurement unit configured to provide tissue impedance measurement to the controller and / or a tissue temperature measurement unit configured to provide tissue temperature measurement to the controller.

[0033] In one aspect of the current disclosure there is a method for treating dry eye disease / syndrome of a subject, the method comprising: providing an energy signal generator, and at least one energy applicator; providing a controller configured to adjust the frequency and / or intensity of the energy signal; applying, at least one first energy signal and at least one second energy signal different from the first energy signal to a target treatment region of a periocular region the subject’s eye; configuring the first energy signal to reach a predetermined target temperature to heat the Meibomian gland of the eye; and configuring the second energy signal to reach a predetermined target temperature to treat collagen fibers in the eye. The method further comprising providing a tissue impedance measurement unit configured to provide tissue impedance measurement to the controller; receiving, by the controller, impedance measurements; and applying the first and second energy signals based on the

[0034] 5

[0035] SUBSTITUTE SHEET (RULE 26) impedance measurements received. Also further comprising providing a tissue temperature measurement unit configured to provide tissue temperature measurement to the controller; receiving, by the controller, temperature measurements; and applying the first and second energy signals based on the temperature measurements received.

[0036] In another aspect there is a method, wherein at least a portion of the first time period and second time period are simultaneous; the at least one electrode is in one of: a monopolar configuration; a bipolar configuration; or a multipolar configuration; and the energy applicator comprises at least one electrode connected to the energy signal generator, the first and second energy signals are radiofrequency (RF) signals, the first energy signal is of a first frequency or frequency range, and the second energy signal is of a second frequency of higher than the first frequency or frequency range.

[0037] In a final aspect there is method comprising: at least one treatment session comprising applying the first energy signal for a first time period and the second energy signal for a second time period; moving the energy applicator in a substantially C-shape over the target treatment region of the subject’s eye; and applying a complementary treatment with an IPL device.

[0038] The foregoing has broadly outlined the features and technical advantages of the present disclosure. It should be appreciated by those skilled in the art that the conception and specific embodiments may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present disclosure. The novel features which are believed to be characteristic of the disclosure, both as to its organization and method of operation, together with further objects and advantages will be better understood from the following description when considered in connection with the accompanying figures. It is to be expressly understood, however, that each of the figures is provided for the purpose of illustration and description only and is not intended as a definition of the limits of the present disclosure.

[0039] BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

[0040] Fig- 1 illustrates a non-limiting exemplary embodiment of a system according to the presently disclosed subject matter.

[0041] Fig- 2 illustrates a non-limiting exemplary embodiment of a method according to the presently disclosed subject matter.

[0042] Fig- 3 illustrates a non-limiting exemplary embodiment of application of the treatment method according to the presently disclosed subject matter.

[0043] 6

[0044] SUBSTITUTE SHEET (RULE 26) DETAILED DESCRIPTION

[0045] Overview

[0046] In an aspect of the present disclosure, it provides a method for treating dry eye disease.. The method may be employed to locally target and heat the Meibomian glands, either directly or indirectly. The heating may help the Meibomian glands expand and help liquefy the contents of the glands, thus facilitating or enabling an ophthalmic or medical practitioner to perform expression of the Meibomian glands.

[0047] The method may further help target and improve the quality of blinking action. The method may help lubricate the cornea by spreading the tears together with the oil secreted by the Meibomian glands over the cornea The lubrication may help to protect the eyes from irritants and foreign objects. Improving the quality of blinking may be achieved through one or more of the following non-limiting approaches: tightening skin of the eyelids and / or the surrounding skin tissue thus enhancing the ability of the eyelids to fully close and enhance blinking. Tightening of the skin may be achieved, for example, by heating collagen fibers to a requisite temperature. The heating may cause the collagen fibers to shrink, which may promote production of new collagen fibers. The new collagen fibers typically tighten the skin.

[0048] Description of Embodiments

[0049] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of nonlimiting example only, with reference to the accompanying drawings.

[0050] The figures depict non-limiting embodiments of the disclosure, for purposes of illustration only. One skilled in the art will readily recognize from the following description that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles of the disclosure described herein.

[0051] Reference is now made to Fig. 1, a block diagram of a non-limiting example of a system 100 for treating dry eye disease / syndrome of a subject, in accordance some embodiments of the present disclosure.

[0052] The system 100 may comprise a handheld probe 110. The handheld probe may have at least one energy applicator 120. An energy applicator 120 may be configured for applying the treatment to a treatment region of the periocular region of the subject’s eye. In some embodiments, the energy signal generator 140 is disposed in the handheld probe 110. Alternatively, the energy signal generator 140 may be disposed outside the handheld probe.

[0053] 7

[0054] SUBSTITUTE SHEET (RULE 26) In some embodiments, the energy applicator 120 applies at least one first energy signal and at least one second energy signal, further described herein, to the periocular region of the subject’s eye 105. In some embodiments, the first and second energy signals are radio frequency (RF) signals. The at least one energy applicator may be mounted on a distal end of the handheld probe 110. The least one energy applicator may be mounted on a disposable tip (not shown) connectable to the distal end of the handheld probe 110.

[0055] The properties of the first energy signal may be selected for locally targeting and heating the Meibomian glands, either directly or indirectly. The heating may help the Meibomian glands expand and may help liquefy the contents of the glands, thus facilitating or enabling an ophthalmic or medical practitioner to perform expression of the Meibomian glands.

[0056] The properties of the second energy signal may be selected for heating collagen fiber to a requisite temperature. The heating may cause the collagen fibers to shrink, which may promote production of new collagen fibers. Tightening of the skin may be achieved, thereby improving blinking by causing the lower and upper eye lid to meet. In some embodiments, the first or second energy signals are aimed at heating the periocular region of the subject’s eye to a temperature between 37° C and 45° C. In another embodiment, the first and second energy signals are aimed at heating the periocular region of the subject’s yes to about 41° C.

[0057] The system 100 may comprise a return pad 130. The return pad 130 is configured to be attached to the subject’s body at a distant location relative to the eye, thereby applying the treatment to the periocular region of the subject’s eye 105 in a monopolar configuration. In some embodiments, return pad 130 is not required and the treatment is a bipolar or multipolar configuration. In some embodiments, the treatment periocular region is a C-shaped path as illustrated in Fig. 3, 110A. This C-shaped path may be up to the eyebrow of the eye. The treated periocular region of the subject’s eye may extend between the supraorbital foramen and anterior lacrimal crest, along the orbital rim.

[0058] The system 100 may comprise an energy signal generator / source 140. In some embodiments, the energy signal generator 140 is an RF energy source. The energy signal generator 140 is configured to generate a first energy signal 142 and a second energy signal 144 applied through the energy applicator 120 and the return pad 130. In some embodiments, the first energy signal 142 is of a first frequency or frequency range and the second energy signal 144 is of a second frequency or frequency range.

[0059] The second frequency or frequency range may be higher than the first frequency or frequency range. In some embodiments, the first energy signal 142 has a frequency of about 1 MHz. In some embodiments, the second energy signal 144 has a frequency of about 4 MHz.

[0060] 8

[0061] SUBSTITUTE SHEET (RULE 26) The first energy and the second energy signals may be configured to treat different depths of the periocular region of the subject’s eye.

[0062] It is noted that the terms “about” or “substantially”, as used herein, mean tolerance of ±10% of the stated value.

[0063] In some embodiments, the at least one energy applicator 120 is at least one electrode connected to an RF signal energy generator 140. The electrode may have a shape and size adapted to apply the treatment to the periocular region of the subject’s eye. The shape of the electrode may be flat or curved. A curved electrode may be convex or concave. The electrode may have a size adapted to the treated periocular region of the subject’s eye. In some embodiments, the electrode has a treatment portion having a substantially spherical or circular shape with a diameter of about 10 mm. In some embodiments, the first energy signal is provided by a first electrode and the second energy signal is provided by a second electrode. In some embodiments, the first and second energy signals are provided, at least in part, by the same electrodes.

[0064] In some embodiments, the at least one energy applicator is covered with an electrically conductive flexible material, thereby facilitating attachment and conductive coupling to the periocular region of the subject’s eye. In some embodiments, there is a coupling agent such as a gel or creme employed to enhance the treatment.

[0065] The system 100 may further comprise a controller 150. In this disclosure, “controller” (in the singular) is understood to mean one or more controllers or processors that may be hosted on a single computer or whether the features and functions of the controller are distributed over a plurality of networked computers. In some embodiments, the controller 150 further comprises associated user interfaces including but not limited to a display or an input which may include a keyboard and / or mouse (not shown).

[0066] The controller 150 may be configured to control the energy signal generator 140 and / or the at least one energy applicator 120. In some embodiments, the system 100 comprises a tissue impedance measurement unit 160. The tissue impedance measurement unit 160 may be configured to measure tissue impedance and provide the tissue impedance measurements to the controller 150. The measurements may enable fine tuning and customization of the first energy signal 142 and / or the second energy signal 144 to the periocular region.

[0067] The controller may be configured to adjust the frequency or / and intensity of the energy signals. For example, the controller 150 may adjust the frequency or / and intensity of the first energy signal 142 and / or the second energy signal 144. The controller 150 may stop the treatment and / or issue an error notification if the controller receives from the impedance

[0068] 9

[0069] SUBSTITUTE SHEET (RULE 26) measurement unit 160 reports of an impedance outside of a requisite range of impedance. In some embodiments, a predetermined impedance is set by the user of the system or suggested by the system.

[0070] The system 100 may further comprise a tissue temperature measurement unit 170. The temperature measurement unit 170 may be configured to measure tissue temperature and provide the tissue temperature measurements to the controller 150. The tissue impedance measurement unit 160 and / or the tissue temperature measurement unit 170 may be located in vicinity of the treated periocular region of the subject’s eye, e.g. at least partially mounted on the handheld probe 110. In some embodiments, the handheld probe comprises the energy applicator 120, the energy signal generator 140, the controller 150, the tissue temperature measurement unit 170 and the tissue impedance measurement unit 160.

[0071] In some embodiments, a predetermined target temperature(s) is / are selected and set in the system, for the energy applicator to achieve in each of the first energy signal and the second energy signal. This predetermined target temperature may also be based on safety limits. In some embodiments, the predetermined temperature is set by the user of the system or suggested by the system. In some embodiments, a power level of the system is monitored, and a predetermined power level of the energy signal generator set by the user or suggested by the system. In some embodiments, the display (not shown) of the system, displays for the user current and / or history of measurements. Therefore, measurements such as, impedance measurements, temperature measurements and power measurements may be displayed during treatment.

[0072] Reference is now made to Fig. 2, a flow chart of non-limiting example of a method 10 for treating dry eye disease of a subject, in accordance some embodiments of the present disclosure.

[0073] The method 10 may comprise providing a first energy signal 10A.

[0074] The method 10 may comprise applying the first energy signal to the periocular region of the subject’s eye 10B. In some embodiments, the first energy signal has a frequency of about 1 MHz. The region may extend between the supraorbital foramen and anterior lacrimal crest, in a substantially C-shape path, for example along the orbital rim. Applying the first energy 10B may be between one to five minutes. In some embodiments, each of the first and second periods may be equal to about three minutes. Applying the first energy may be done over a single sweep or multiple sweeps in a C-shaped motion 110A. In some embodiments, an area of the upper eyelid is treated. In some embodiments, area of the lower eyelid is treated. In some embodiments, an area of the upper eyelid and an area of the lower eyelid are treated.

[0075] 10

[0076] SUBSTITUTE SHEET (RULE 26) The method 10 may comprise providing a second energy signal 10C. The second energy signal may be different from the first energy signal. For example, the second energy signal may have a higher frequency than the first energy signal. In some embodiments, the second energy signal has a frequency of about 4 MHz.

[0077] The method 10 may comprise applying the second energy signal to the periocular region of the subject’s eye 10D. In some embodiments, the method comprises moving the energy applicator in a substantially C-shape or similar path over the periocular region of the subject’s eye. The C-shape may be up to the eyebrow of the eye. The C-shaped region may extend between the supraorbital foramen and anterior lacrimal crest, in a substantially C-shape path along the orbital rim, for a period of between one to five minutes. In some embodiments, each of the first and second periods may be equal to about three minutes.

[0078] The first and second energy signals may each be applied in a monopolar, bipolar, and / or multipolar configuration.

[0079] In some embodiments, steps 10B and 10D are performed simultaneously, as, for example, where first and second energy applicators, providing the first and second energy signal, respectively, are attached to the same system. In some embodiments, the method comprises repeating steps 10A through 10D on the periocular region of a subject’s second eye. In some embodiments, steps 10A through 10D are repeated periodically for a predetermined number of treatment sessions. In some embodiments, the system may comprise an IPL unit configured to provide complementary treatment.

[0080] In the present document, the word "exemplary" is used herein to mean "serving as an example, instance, or illustration." Any embodiment or implementation of the present subject matter described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

[0081] The terms “comprises”, “comprising”, or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a mechanism that comprises a list of components does not include only those components but may include other components not expressly listed or inherent to such mechanism. In other words, one or more elements in the device or mechanism preceded by “comprises... a” does not, without more constraints, preclude the existence of other elements or additional elements in the mechanism.

[0082] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity.

[0083] 11

[0084] SUBSTITUTE SHEET (RULE 26) Various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting.

[0085] 12

[0086] SUBSTITUTE SHEET (RULE 26)

Claims

CLAIMS1. A system for treating dry eye disease of a subject, comprising: a controller configured to adjust frequency or / and intensity of energy signals; an energy signal generator; at least one energy applicator configured to receive the energy signals from the energy signal generator, to apply a first energy signal and a second energy signal different from the first energy signal to a target treatment region of a periocular region of the subject’s eye, wherein the first energy signal is configured to reach a predetermined target temperature to heat Meibomian glands of the eye and the second energy signal is configured to reach a predetermined target temperature to treat collagen fibers.

2. A system according to claim 1, wherein the energy applicator comprises at least one electrode connected to the energy signal generator, the first and second energy signals are first and second radio frequency (RF) signals, the first RF signal is of a first frequency or frequency range, and the second RF signal is of a second frequency or frequency range higher than the first frequency or frequency range.

3. A system according to claim 2, wherein the first RF signal has a frequency of about 1 MHz, the second RF signal has a frequency of about 4 MHz, and both the first and second RF signals are applied to the target treatment region by the at least one electrode.

4. The system according to claim 2, wherein the first and second RF signal applications utilize at least one of: a monopolar configuration; a bipolar configuration; or a multipolar configuration.

5. The system according to claim 2, wherein the at least one electrode is one electrode configured to apply both the first and second RF signal.

6. The system according to claim 2, wherein the at least one electrode is / are one of: a flat electrode; a curved electrode; a curved convex electrode; or a curved concave electrode.13RECTIFIED SHEET (RULE 91)7. The system according to claim 1 , wherein the system is a handheld probe, and the handheld probe comprises the at least one energy applicator configured to be mounted on a distal end of the handheld probe and the handheld probe is further configured for manipulation by a user to apply the treatment to the target treatment region.

8. The system according to claim 5, wherein the energy signal generator is disposed in the handheld probe or outside the handheld probe.

9. The system of claim 1 , wherein the controller is configured to apply the at least first energy signal and the at least one second energy signal simultaneously.

10. A system according to claim 1, wherein the second energy signal targets the subject’s eyelid region in order to improve the blinking quality of the subject’s eye.

11. A system according to claim 1, wherein the at least one energy applicator is covered with a flexible electrically conductive material, thereby enhancing coupling and attachment to the treated target treatment region.

12. A system according to claim 1, comprising a tissue impedance measurement unit configured to provide tissue impedance measurement to the controller.

13. A system according to claim 1, comprising a tissue temperature measurement unit configured to provide tissue temperature measurement to the controller.

14. A method for treating dry eye disease / syndrome of a subject, the method comprising: providing an energy signal generator, and at least one energy applicator; providing a controller configured to adjust the frequency and / or intensity of the energy signal; applying, at least one first energy signal and at least one second energy signal different from the first energy signal to a target treatment region of a periocular region the subject’s eye; and configuring the first energy signal to reach a predetermined target temperature to heat the Meibomian gland of the eye; and configuring the second energy signal to reach a predetermined target temperature to treat collagen fibers in the eye.

15. The method according to claim 12, further comprising: providing a tissue impedance measurement unit configured to provide tissue impedance measurement to the controller; receiving, by the controller, impedance measurements; and applying the first and second energy signals based on the impedance measurements received.14RECTIFIED SHEET (RULE 91)16. The method according to claim 12, further comprising: providing a tissue temperature measurement unit configured to provide tissue temperature measurement to the controller; receiving, by the controller, temperature measurements; and applying the first and second energy signals based on the temperature measurements received.

17. The method according to claim 12, comprising at least one treatment session comprising applying the first energy signal for a first time period and the second energy signal for a second time period.

18. The method according to claim 15, wherein at least a portion of the first time period and second time period are simultaneous.

19. The method of claim 12, comprising moving the energy applicator in a substantially C- shape over the target treatment region of the subject’s eye.

20. The method of claim 12, further comprising applying a complementary treatment with an IPL device.

21. The method of claim 12, wherein the energy applicator comprises at least one electrode connected to the energy signal generator, the first and second energy signals are radiofrequency (RF) signals, the first energy signal is of a first frequency or frequency range, and the second energy signal is of a second frequency of higher than the first frequency or frequency range.

22. The method of claim 19, wherein the at least one electrode is in one of: a monopolar configuration; a bipolar configuration; or a multipolar configuration.15RECTIFIED SHEET (RULE 91)

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