Method and apparatus for treatment of diabetic retinopathy (DR)

Abstract

A method for anti-inflammatory treatment of diabetic retinopathy can include systemic administration of an A2aAR agonist and providing local electric field stimulation to the retina. The electric field stimulation causes translocation of A2aRs from cytosol to the cell membranes and makes them active and available for binding with adenosine and adenosine agonists. Increased numbers of active A2aRs on cellular membranes leads to several-fold increase in the anti-inflammatory signal transduced into the cells. Amplified adenosine-A2aR signaling pathway causes significant inhibition of production of proinflammatory cytokines and other cytotoxic activity of microglia thus protecting the retina from destruction by the immune system and preserving eyesight. A treatment apparatus can include a multicoil applicator with coils adapted for positioning near eyes for stimulating retina, a pulse generator functionally coupled to the applicator and a power supply.

Claims

1. A pulsed electro-magnetic field (PEMF) stimulation apparatus for treatment of diabetic retinopathy (DR), the apparatus comprising: a frame; a first coil provided to the frame and positioned adjacent to a first eye of the user; a second coil provided to the frame and positioned adjacent to a second eye of the user; and a controller coupled to each of the first coil and the second coil and configured to periodically switch directions of an electric current in the first coil and the second coil during a treatment regimen.

2. The apparatus of claim 1, wherein the first and second coils are each disposed in front of the eyes of the user.

3. The apparatus of claim 1, wherein the first and second coils are each disposed beside a respective temple area of the user.

4. The apparatus of claim 1, wherein the frame is configured as a pair of eyeglasses.

5. The apparatus of claim 1, wherein the frame is configured as a pair of safety goggles.

6. The apparatus of claim 1, wherein the frame is configured as a flexible arc clip configured to secure the frame to the head of the patient.

7. The apparatus of claim 1, wherein the frame is configured to rest on a nose bridge of a user.

8. A pulsed electro-magnetic field (PEMF) stimulation apparatus for treatment of diabetic retinopathy (DR), the apparatus comprising: a frame; a first coil provided to the frame and positioned adjacent to a first eye of the user; a second coil provided to the frame and positioned adjacent to a second eye of the user; a third coil provided to the frame and positioned adjacent to the first eye of the user in a different plane than the first coil; and a fourth coil provided to the frame and positioned adjacent to the second eye of the user in a different plane than the second coil, and a controller coupled to each of the first coil, the second coil, the third coil and the fourth coil, and configured to periodically switch directions of an electric current in the first coil and the second coil during a treatment regimen.

9. The apparatus of claim 8, wherein the first and second coils are each disposed in front of the eyes of the user, and wherein the third and fourth coils are each disposed along side a respective temple area of the user.

10. The apparatus of claim 8, wherein the controller is configured to alternate pulses between the first and third coils, and alternate pulses between the second and fourth coils.

11. The apparatus of claim 8, wherein the first and second coils are each disposed in front of the eyes of the user.

12. The apparatus of claim 8, wherein the first and second coils are each disposed beside a respective temple area of the user.

13. The apparatus of claim 8, wherein the frame is configured as a pair of eyeglasses, a pair of safety goggles, or as a flexible arc clip configured to secure the frame to the head of the patient.

14. The apparatus of claim 8, wherein the frame is configured to rest on a nose bridge of a user.

15. A pulsed electro-magnetic field (PEMF) stimulation apparatus for treatment of diabetic retinopathy (DR), the apparatus comprising: a frame; a first coil provided to the frame and positioned adjacent to a first eye of the user; a second coil provided to the frame and positioned adjacent to a second eye of the user; a third coil provided to the frame and positioned adjacent to the first eye of the user in a different plane than the first coil; and a fourth coil provided to the frame and positioned adjacent to the second eye of the user in a different plane than the second coil, and a controller coupled to each of the first coil, the second coil, the third coil and the fourth coil, and configured to alternate pulses between the first and third coils, and alternate pulses between the second and fourth coils, during a treatment regimen.

16. The apparatus of claim 15, wherein the first and second coils are each disposed in front of the eyes of the user, and wherein the third and fourth coils are each disposed along side a respective temple area of the user.

17. The apparatus of claim 15, wherein the first and second coils are each disposed in front of the eyes of the user.

18. The apparatus of claim 15, wherein the first and second coils are each disposed beside a respective temple area of the user.

19. The apparatus of claim 15, wherein the frame is configured as a pair of eyeglasses, a pair of safety goggles, or as a flexible arc clip configured to secure the frame to the head of the patient.

20. The apparatus of claim 15, wherein the frame is configured to rest on a nose bridge of a user.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 depicts an apparatus for treatment of diabetic retinopathy shown as being worn by a patient according to certain embodiments.

(2) FIG. 2 is a perspective view of an apparatus for treatment of diabetic retinopathy with a goggles-like frame according to certain embodiments.

(3) FIG. 3 is a view of a treatment apparatus with an over-the-head clip on the head of a patient according to certain embodiments.

(4) FIG. 4 is a series of four schematics depicting the spatial patterns of pulsed magnetic and electric fields during PEMF stimulation of a diabetic patient's eyes according to certain embodiments.

(5) FIG. 5 is a series of diagrams of wave forms of pulses generated by a controller during stimulation of a patient's diabetic eyes according to certain embodiments.

(6) FIG. 6 is a perspective view of a treatment apparatus suitable for office or home use according to certain embodiments.

(7) While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular example embodiments described. On the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION

(8) In the following descriptions, the present invention will be explained with reference to various example embodiments; nevertheless, these example embodiments are not intended to limit the present invention to any specific example, embodiment, environment, application, or particular implementation described herein. Therefore, descriptions of these example embodiments are only provided for purpose of illustration rather than to limit the present invention.

(9) Diabetic retinopathy progresses through four stages: mild nonproliferative retinopathy, moderate nonproliferative retinopathy, severe nonproliferative retinopathy and proliferative diabetic retinopathy (PDR). The method of treatment of DR provided herein can be effective in all three nonproliferative stages of the disease, and the earlier stage the better.

(10) An apparatus for treatment of diabetic retinopathy 100 is shown in FIG. 1. A glasses-like frame 101 formed of insulating material rests on the nose bridge of a patient and is secured on his head with a belt or strap 102. Numerals 103 and 104 designate the electromagnetic coils positioned at the front side of the right and left eyes correspondingly. Further electromagnetic coils 105 and 106 are secured at the right and the left sides of the glasses-like frame 101. A multi-conductor cable 107 functionally connects all four coils 103, 104, 105 and 106 with a computerized controller 108 that provides to each coil electrical pulses with predetermined sequence, amplitude, polarity, and repetition rate. Power cable 109 connects controller 108 with a battery or another power source 110.

(11) Controller 108 generates rectangular (DC) pulses that are applied in predetermined sequence to the coils 103, 104, 105 and 106, creating changing magnetic fields inside of the coils. The duration of the pulses is required to be more than the time of electrical relaxation of a biological cell, which is about 1 microsecond. Practically employed durations can be in the range of 10 to 1000 microseconds. The time of relaxation of the coil τ=L/R, where L is inductance of the coil and R is it's resistance, is selected to be at least several times higher than the duration of the pulses, which leads to close to linear growth of the current and magnetic field and makes corresponding electrical field pulses generated by the changing magnetic fields approximately rectangular.

(12) The electrical field pulses applied to the retina via the coils cause the electrically sensitive adenosine A2aR receptors to translocate to the surface of the cellular membranes, where they bind with free adenosine or adenosine like drugs from the intercellular space. This process activates in parenchymal and macroglial cells of the retina the adenosine-A2aR anti-inflammatory signaling pathway which is the major objective of the present invention.

(13) In another implementation of the invention, only the two coils 103 and 104 in front of the eye can be used, without side coils 105 and 106, or vice versa, with only the side coils 105 and 106 without the front coils 103, 104.

(14) Also, side coils 105 and 106 can be configured as attachable and removable “clips” that can be used with standard vision glasses.

(15) In FIG. 2 another implementation of the treatment apparatus 200 is shown. Here the PEMF stimulating coils 105, 106 are secured on a protecting goggles-like frame which can be put over the patient's standard glasses while wearing the glasses. In this implementation the side coils 105 and 106 are located proximately to the eyes exactly as in FIG. 1, but instead of two front coils 103 and 104 only one front coil 201 is provided.

(16) FIG. 3 illustrates another embodiment of the treatment apparatus 300 where the side coils 105 and 106 are held in close proximity to the patient's eyes by a flexible arc clip 301 which secures the coils to the head of the patient. This PEMF system 300 also can be used simultaneously with standard glasses.

(17) In the embodiment of FIG. 1, the sequence of pulses delivered by the controller to the coils 103, 104, 105 and 106 is exemplary illustrated by sequence a), b), c), d) in FIG. 4. Cycles a) and b) are activated consecutively in sequence “front-side-front-side” etc. It should be mentioned that different pulse sequences can be selected, as well as the durations of each cycle with a given mode of pulsing. Straight arrows show the direction of magnetic field B in each coil and circular arrows show the direction of the electrical field E induced in the retina.

(18) In an exemplary implementation of the invention the duration of cycles a) and b) may last around 10-15 minutes with switching every 10-15 minutes to opposite polarity of magnetic and electric fields in cycles c) and d), up to 30-40 minutes per session. The 10-15 minute pauses between applying electrical field pulses of different polarities leave newly activated A2aRs undisturbed about 10-15 minutes which allows them to bind with adenosine and contribute to activation of the adenosine-A2aR anti-inflammatory pathway.

(19) Two-dimensional PEMF stimulation is employed with opposite polarities of pulsing to allow increasing the number of A2aRs on the cells available for binding by a factor of 3-4 times as compared to the base number. As was demonstrated by Katia Varani et al., the downstream anti-inflammatory action of adenosine-A2aR pathway increases as the square of the number of the receptors. This means that the 3-4 increase in number of activated receptors increases anti-inflammatory action by 9-16 times. The same anti-inflammatory action cannot be achieved pharmaceutically by increasing concentration of adenosine 9-16 times because of side effects of the drugs employed for controlling the anti-inflammatory response. The efficient level of anti-inflammatory treatment was demonstrated to be 4-5 times that of the base level.

(20) FIG. 5 illustrates waveforms of the pulses generated on the coils 103, 104, 105 and 106 and in the treatment zone. FIG. 5 at (a) is a diagram of voltage V(t) applied to the coils; (b) depicts the electric current I(t) through coils and magnetic field B(t) at the treatment zone; and (c) depicts the electric field E(t) in the treatment zone. The duration of the pulses t.sub.p lies in the range from 10 to 1000 microseconds. The period T between sequential pulses is in the 10 to 200 millisecond range, which corresponds to frequency (repetition rate) range f=5-100 Hertz. FIG. 5 depicts only positive polarity of the pulses. The negative polarity pulses could also be used in the PEMF system.

(21) In FIG. 6 another implementation of the treatment apparatus 600 is schematically depicted. This version of the apparatus is not portable but rather stationarily secured on a therapeutic chair 601. Chair 601 has a head support 602 on which adjustable mounts 603 and 604 are attached. At the ends of mounts 603 and 604 applicators 605 and 606 are secured. Each applicator 605, 606 includes preferably three coils that during a treatment session are positioned in close proximity to the patient's eyes while sitting in the chair. The spatial positions of the coils to each other are selected in such a manner that they provide electrical stimulation of the patient's eyes in three orthogonal directions, thus providing maximum possible effect of stimulation. Multi wire cable 607 connects applicators 605 and 606 with computerized controller 608 attached to a shelf 609 secured to chair 601. Power cable 610 is connected to a connector 611.

(22) It is also within the scope of the invention to combine features, functions, advantages and aspects of the various embodiments described herein. Thus, the embodiments of the invention may comprise combinations of aspects of any one or more of these exemplary embodiments.

(23) While the invention has been described in connection with what is presently considered to be the most practical and preferred example embodiments, it will be apparent to those of ordinary skill in the art that the invention is not to be limited to the disclosed example embodiments. It will be readily apparent to those of ordinary skill in the art that many modifications and equivalent arrangements can be made thereof without departing from the spirit and scope of the present disclosure, such scope to be accorded the broadest interpretation of the appended claims so as to encompass all equivalent structures and products.

(24) For purposes of interpreting the claims for the present invention, it is expressly intended that the provisions of Section 112, sixth paragraph of 35 U.S.C. are not to be invoked unless the specific terms “means for” or “step for” are recited in a claim.