Method for improving retinal blood circulation using radio frequency (RF) microwaves, RF emitting circuit using the same and use thereof

Abstract

A method for improving blood circulation using radio frequency (RF) microwaves, RF emitting circuit using the same and use thereof is provided to apply treatment without thermal effect to an eye by emitting the RF microwaves with a frequency between 30MHz and 1000MHz, thereby substantially imperceptibly regulating retinal VD. That is, it can increase the too low blood vessel density and reduce the too high blood vessel density, thereby optimizing the blood flow distribution of retinal capillary to improve blood circulation.

Description

[Technical Field]

[0001] This case relates to bioelectromagnetic technology, and in particular to a method for promoting retinal blood circulation using radio frequency (RF) microwaves, a radio frequency transmitting device using the method, and its uses. [Previous Technology]

[0002] Due to the expansion of radio frequency (RF) technology, electronic devices using RF technology (hereinafter referred to as RF devices) have experienced rapid growth in applications related to the human body, such as medical care, beauty, health care, and nursing.

[0003] In non-medical applications (such as beauty, home health care, or home nursing), energy-based radiofrequency devices act on the human body or epidermis in a non-invasive or invasive manner through electrodes. Non-invasive radiofrequency devices utilize electrodes attached to the skin to generate a radiofrequency current thermal effect on the skin tissue, thereby inducing reversible denaturation of collagen in the dermis and stimulating the formation of new collagen during the healing process, thus producing a lifting and firming effect on the skin. Invasive radiofrequency devices use a positive electrode head to contact the treatment area, while the negative electrode is a conductive negative plate that contacts another part of the body. Invasive radiofrequency devices apply radiofrequency energy through positive and negative electrodes, and this energy can radiate from the epidermis downwards into the subcutaneous tissue, resulting in deeper penetration and enhancing the skin-tightening effect. [Summary of the Invention]

[0004] However, when radio frequency (RF) devices are used by directly contacting the skin or treatment site with metal electrodes, the RF current acts directly on the human body, which can easily cause stinging and discomfort, and can also lead to excessively high local skin temperature, posing a certain risk of burns. Furthermore, existing RF devices cannot be used to improve retinal blood circulation. This is because the eyeball structure is delicate and fragile, and cannot withstand high temperatures. The retina, in particular, located at the back of the eye, is extremely sensitive to temperature changes; excessively high temperatures can cause irreversible damage. Therefore, to date, there is no effective and safe device or method to directly improve retinal blood circulation. However, due to the extensive and prolonged use of 3C products, the workload and blood supply requirements of the retina will be significantly increased. Therefore, whether non-thermal effects can be used to promote retinal blood circulation has become a major issue in vision care.

[0005] In view of the above, the present invention provides a method for regulating retinal blood vessel density using radio frequency microwaves to promote blood circulation, a radio frequency transmitting device using the method, and its use, which can apply a non-thermal effect to the eye by transmitting radio frequency microwaves with a frequency between 30MHz and 1000MHz, thereby avoiding the stinging sensation, discomfort and / or excessive local temperature caused by the direct action of radio frequency devices on the human body, and providing the effect of regulating retinal blood vessel density to promote blood circulation.

[0006] In some embodiments, a method of using radio frequency microwaves to modulate retinal blood vessel density to promote blood circulation includes: positioning a radio frequency transmitting device within a range of 3 cm to 10 cm from the eye; driving the radio frequency transmitting device to emit radio frequency microwaves, wherein the frequency of the radio frequency microwaves is between 30 MHz and 1000 MHz; and applying a non-thermal effect to the retinal region of the eye using the radio frequency microwaves.

[0007] In some embodiments, the aforementioned radio frequency transmitting device is a passive radio frequency circuit.

[0008] In some embodiments, the aforementioned radio frequency transmitting device is an active radio frequency circuit.

[0009] In some embodiments, the aforementioned radio frequency transmitting device is an eyeglass clip or a pair of glasses.

[0010] In some embodiments, a radio frequency transmitting device is used for modulating retinal vascular density to promote blood circulation, wherein the radio frequency transmitting device is used to generate radio frequency microwaves with a frequency between 30 MHz and 1000 MHz.

[0011] In some embodiments, a radio frequency transmitting device for adjusting retinal blood vessel density includes a transmitting module and a control module. The control module is connected to the transmitting module and configured to generate radio frequency microwaves with a frequency between 30 MHz and 1000 MHz via the transmitting module.

[0012] In some embodiments, the aforementioned control module is a passive chip.

[0013] In some embodiments, the aforementioned radio frequency transmitting device further includes a power supply module. This power supply module is connected to the control module and configured to supply power to the control module.

[0014] In some embodiments, the aforementioned radio frequency transmitting device further includes: glasses, and the transmitting module and control module are disposed on the glasses.

[0015] In summary, the method for promoting retinal blood circulation using radio frequency microwaves in any embodiment, the radio frequency transmitting device using the method, and its use can apply non-thermal stimulation to the eye by transmitting radio frequency microwaves with a frequency between 30MHz and 1000MHz, thereby providing a substantially imperceptible adjustment of retinal blood vessel density and thus improving blood circulation.

Implementation Method

[0016] Referring to Figure 1, a radio frequency (RF) transmitter 10 is used to generate a non-thermal radio frequency microwave EF. Specifically, the RF transmitter 10 can be positioned non-contactly around the eye 20 to be affected and generates an electromagnetic field (i.e., the radio frequency microwave EF) to expose the eye 20 to the generated electromagnetic field, thereby generating a non-thermal effect on the retinal region of the eye 20 using a non-contact electromagnetic field. Here, the frequency of the radio frequency microwave EF is between 30MHz and 1000MHz.

[0017] In some embodiments, referring to FIG1, the radio frequency transmitting device 10 includes a transmitting module 110 and a control module 120. The control module 120 is connected to the transmitting module 110 and is configured to generate radio frequency microwaves EF with a frequency between 30MHz and 1000MHz and a signal strength between 10dBμV and 30dBμV via the transmitting module 110. In other words, the frequency of the radio frequency microwaves EF is within the bandwidth range of Ultra High Frequency (UHF).

[0018] In some embodiments, the frequency of the radio frequency microwave EF may be between 600MHz and 1000MHz. In some embodiments, the frequency of the radio frequency microwave EF may be about 900MHz.

[0019] In some embodiments, the operating distance DR of the radio frequency transmitting device 10 is between 3 cm and 10 cm.

[0020] In some embodiments, during use, the radio frequency transmitting device 10 is first positioned within a range of 3 cm to 10 cm from the eye 20, and then the radio frequency transmitting device 10 is driven to emit radio frequency microwaves EF, such that the emitted radio frequency microwaves EF provide non-thermal stimulation to the retinal region of the eye 20. In some embodiments, for retinal regions with excessively low vascular density, the radio frequency microwaves EF emitted by the radio frequency transmitting device 10 can promote angiogenesis in the retinal region through non-thermal stimulation to increase its vascular density. For retinal regions with excessively high vascular density, the radio frequency microwaves EF emitted by the radio frequency transmitting device 10 can promote angiogenesis in the retinal region through non-thermal stimulation to increase its vascular density.

[0021] In some embodiments, when the radio frequency transmitting device 10 applies non-thermal radio frequency microwaves EF to the eye 20 (even when the eye 20 is exposed to the electromagnetic field generated by the radio frequency transmitting device 10), it can produce an effect that modulates the vascular density (VD) of the retinal region of the eye 20. Therefore, this radio frequency transmitting device 10 is suitable for fabricating devices for modulating retinal vascular density (e.g., wireless radio frequency devices or wearable devices). In some embodiments, the blood vessels may be microvessels.

[0022] Specifically, retinal vascular density refers to the density of the vascular network in the retina. Insufficient retinal vascular density and excessive new blood vessels can both adversely affect eye health. Therefore, the radiofrequency emission device 10 can be used for non-medical eye care purposes to increase the vascular density in low vascular density areas (Low VD Area) without causing an abnormal increase in the microvascular density of normal areas, thereby promoting blood circulation. According to the Taiwan Food and Drug Administration's FDA Approval No. 1010032059, "promoting blood circulation" is not considered a medical function.

[0023] In some embodiments, excessively low vascular density creates non-flow areas on the retina, thereby reducing blood supply to the retina and causing hypoxia. Prolonged hypoxia can damage retinal cells, particularly photoreceptor cells, leading to decreased vision. In some cases, low vascular density is associated with various eye diseases such as glaucoma, diabetic retinopathy subtypes, age-related macular degeneration, or severe myopia. Therefore, in some embodiments, the radiofrequency transmitting device 10 can also be used to improve or avoid non-flow areas to treat or prevent various eye diseases such as glaucoma, diabetic retinopathy subtypes, age-related macular degeneration, or severe myopia.

[0024] In addition, patients without eye diseases may experience low retinal vascular density due to changes in their internal environment caused by their diseases. For example, excessively high blood sugar in diabetic patients can cause damage to the vascular endothelium and long-term damage to the microvascular system. As another example, cardiovascular diseases or COPD can cause chronic ischemia, hypoxia, and / or hypercapnia, thus exacerbating retinal vascular atrophy. Therefore, in some embodiments, the radio frequency transmitting device 10 can also be used to reduce the damage to vascular endothelial cells caused by stress environments.

[0025] In some embodiments, the aforementioned radio frequency transmitting device 10 may be a standalone wireless radio frequency device 10', as shown in FIG2. Specifically, referring to FIG2, the wireless radio frequency device 10' includes a radio frequency circuit 11 and a housing 12. The radio frequency circuit 11 is located inside the housing 12, that is, disposed in the accommodating space inside the housing 12. Here, the radio frequency circuit 11 is used to transmit radio frequency microwaves EF with a frequency between 30MHz and 1000MHz. When using the wireless radio frequency device 10', the housing 12 can be fixed to the wearable device 30 by means of adhesion, locking, snapping, or clamping. Based on this, the user can assemble the wireless radio frequency device 10' onto the wearable device 30 only when needed, making the use of the radio frequency transmitting device 10 more convenient. In an exemplary example, referring to FIGS. 2 and 3, taking the wearable device 30 as glasses as an example, the radio frequency transmitting device 10 may be a glasses clip (i.e., the wireless radio frequency device 10' is a glasses clip). Herein, the radio frequency circuit 11 is disposed within the housing 12 of the wireless radio frequency device 10', and a clamping member 14 is provided on an outer surface of the housing 12. In use, the temples 31 of the glasses are clamped between the housing 12 and the clamping member 14, thereby fixing the wireless radio frequency device 10' to the glasses. The structural design of the clamping member 14 is well known in the art and will not be described in detail.

[0026] In some other embodiments, the aforementioned radio frequency transmitting device 10 may also be a wearable device 30', that is, one of the components of the wearable device 30' is a radio frequency circuit 11 having the aforementioned functions, as shown in FIG4. For example, taking eyeglasses as an example, the wearable device 30' has a radio frequency circuit 11 embedded inside the eyeglasses (e.g., eyeglass frame or lens 35), and this radio frequency circuit 11 can transmit radio frequency microwaves EF with a frequency between 30MHz and 1000MHz. Specifically, the radio frequency circuit 11 may be embedded in the temple 31 of the eyeglass frame (as shown in FIG4) or embedded in the lens frame 33 or lens 35 of the eyeglass frame (not shown).

[0027] In some embodiments, the temple 31 has a connecting end 31a and an ear loop end 31b. The temple 31 is coupled to the lens frame 33 (as shown in Figures 2 and 3) or the lens 35 (not shown) via the connecting end 31a. Here, the radio frequency circuit 11 for transmitting radio frequency microwaves EF can be disposed on the connecting end 31a of the temple 31. For example, the wireless radio frequency device 10', which is the radio frequency transmitting device 10, is removably assembled on the connecting end 31a of the temple 31 (as shown in Figures 2 and 3), or the radio frequency circuit 11 is directly embedded in the connecting end 31a of the temple 31 (as shown in Figure 4).

[0028] In some embodiments, in addition to the aforementioned glasses, the wearable device 30 / 30' may also be a headwear, hat, or mask, etc., worn on the head; however, the present invention is not limited thereto.

[0029] In some embodiments, the radio frequency circuit 11 can be implemented on a circuit board 101, as shown in FIG5. In other words, referring to FIG1 and FIG5, the radio frequency circuit 11 includes a circuit board 101, a transmitting module 110 formed on the surface 101a of the circuit board 101, and a control module 120 disposed on the circuit board 101. The circuit board 101 may be a single-layer board or a multi-layer board.

[0030] In some embodiments, the transmitting module 110 is composed of an antenna pattern 130 and a matching pattern 140 (as shown in FIG. 5), but is not limited thereto. In practical applications, the transmitting module 110 may also be composed of only the antenna pattern 130, or it may be composed of the antenna pattern 130 and one or more signal processing components such as the matching pattern 140, an amplifier, and a filter. Referring to FIG. 5, the matching pattern 140 and the antenna pattern 130 may be circuit traces on any surface 101a of the circuit board 101.

[0031] In some embodiments, the control module 120 may be an RF chip 120', as shown in FIG5. The RF chip 120' is an electronic component electrically connected to the circuit traces of the matching pattern 140 and fixed (or soldered) on the circuit board 101.

[0032] In some embodiments, the number of antenna patterns 130 is two, and the two antenna patterns 130 are symmetrical to each other. Here, the two antenna patterns 130 have similar back-and-forth bending structures 132. The back-and-forth bending structure 132 of each antenna pattern 130 has a plurality of vertical traces arranged along a first direction D1 and extending along a second direction D2. The number of vertical traces of each antenna pattern 130 is at least greater than 10 (e.g., 15). The RF chip 120' is coupled to one side of the matching pattern 140 (hereinafter referred to as the first side). The first end of the back-and-forth bending structure 132 of each antenna pattern 130 is coupled to the first side of the matching pattern 140 via a connecting trace 136. Each antenna pattern 130 also has a horizontal trace 134 extending along the first direction D1. The first end of the horizontal trace 134 of each antenna pattern 130 is coupled to the second end of its zigzag structure 132, and the second end of the horizontal trace 134 is a free end and is close to the matching pattern 140 relative to its free end. The first end and the second end of the zigzag structure 132 of each antenna pattern 130 are located at opposite corners of the zigzag structure 132.

[0033] In some other embodiments, the radio frequency transmitting device 10 can be implemented as a combination of a circuit board and a metal sheet (not shown). Specifically, the matching pattern 140 can be a circuit trace on any surface 101a of the circuit board 101. The radio frequency chip 120' is an electronic component fixed (or soldered) to the circuit trace on the circuit board 101, thereby electrically connecting to the matching pattern 140. Here, the antenna pattern 130 is made of a metal sheet, and the signal feed point on the metal sheet is directly soldered or connected via wires to the circuit trace on any surface 101a of the circuit board 101, thereby electrically connecting to the matching pattern 140.

[0034] In some embodiments, the radio frequency transmitting device 10 may be passive, i.e., the radio frequency circuit 11 is a passive radio frequency circuit. That is, the radio frequency chip 120' is a passive chip. In this case, the radio frequency chip 120' can sense the ambient electromagnetic field through the antenna pattern 130 and be driven. That is, the radio frequency transmitting device 10 can sense and respond to the ambient electromagnetic field to drive and emit radio frequency microwaves EF through the antenna pattern 130, thereby applying non-thermal stimulation to the retinal region of the eye 20, thereby regulating the retinal blood vessel density of the eye 20. In some embodiments, according to the measurement method of CIPR 11 Class B, the signal strength (i.e., the electric field strength of the electromagnetic field) of the radio frequency microwaves EF emitted by the passive radio frequency circuit can be between 10 dBμV / m and 30 dBμV / m.

[0035] In some other embodiments, the radio frequency transmitting device 10 may be active, that is, the radio frequency circuit 11 is an active radio frequency circuit. In other words, the radio frequency chip 120' is an active chip. Referring to FIG6, the radio frequency transmitting device 10 may further include a power supply module 150, and this power supply module 150 is connected to the control module 120 (e.g., connected to the radio frequency chip 120'). In use, the power supply connection outputs power to the control module 120, causing the control module 120 to emit radio frequency microwaves EF via the transmitting module 110, thereby applying non-thermal stimulation to the retinal region of the eye 20, and thus regulating the retinal blood vessel density of the eye 20. In some embodiments, the signal power of the active radio frequency circuit is 0 dBm (decibel milliwatt) to 30 dBm.

[0036] Example 1: Human Trials

[0037] A. Conditions of the subject

[0038] The inclusion criteria for subjects were: open to both men and women, aged 40-85, requiring at least 8 hours of daily glasses wear, and experiencing recent vision decline and / or eye fatigue. Furthermore, subjects were required to be able to undergo optical coherence tomography angiography (OCTA) with clear and recognizable images.

[0039] The exclusion criteria for subjects are: having undergone ophthalmic surgery for diabetic retinopathy, having an intraocular pressure exceeding 21 mmHg, failing to be tested according to the trial schedule, being unable to perform fundus microvascular photography or having poor image quality, and developing new eye diseases and / or receiving new drug treatments during the trial.

[0040] B. Design of radio frequency transmitting device 10

[0041] The eyeglass clip in the experimental group is a wireless radio frequency device 10' with the radio frequency circuit 11 shown in Figure 5, as shown in Figures 2 and 3. The eyeglass clip in the control group only has a shell (i.e., housing 12 and clamping member 14), but does not have the radio frequency circuit 11.

[0042] The radio frequency chip 120' of the radio frequency circuit 11 is a passive UHF radio frequency transmitter (IMPINJ MONZA R6), with its operating frequency set at 900MHz and the output signal strength set at 20dBμV. During the test, the radio frequency chip 120' transmits radio frequency microwaves EF through the antenna pattern 130 at a frequency of once per second, and the duration of each transmission is 0.1 seconds.

[0043] In accordance with the CISPR 11 Class B testing standard, the electromagnetic radiation (radiated emission) of the eyeglass clips in the experimental group was tested using the QP (QUASI-PEAK) detection mode. The measurement results are shown in Table 1 and Figure 7. Following the CISPR 11 Class B testing standard indicates that the tested product belongs to industrial, scientific, or medical radio frequency equipment suitable for residential use. As can be seen from Table 1 and Figure 7, the radio frequency microwave EF radiated by the radio frequency circuit 11 exhibits pulses S1~S6 at six frequency points, and the electric field strength of these pulses S1~S6 does not exceed the limit. Therefore, the emission frequency range of the radio frequency microwave EF of this radio frequency circuit 11 is between 30MHz and 1000MHz.

[0044] Table 1 Freq. (MHz) Read value (dBμV) CF (dB / m) Measurement value (dBμV / m) Limit (dBμV / m) Over (dB) S1 30.00 20.80 -2.30 18.50 40.00 -21.50 S2 133.24 20.50 -8.99 11.51 40.00 -28.49 S3 418.32 20.90 -3.34 17.56 47.00 -29.44 S4 659.09 21.70 -0.83 20.87 47.00 -26.13 S5 822.77 21.70 1.07 22.77 47.00 -24.23 S6 911.07 21.60 2.09 23.69 47.00 -23.31

[0045] In Table 1, the column “Freq.” represents the frequency point; the column “Reading Level” represents the value read from the testing instrument; the column “CF” is the correction factor; the column “Measured Value” represents the final value of each frequency point after confirmation; the column “Limit” represents the limit, that is, the measured value cannot exceed this limit; and the column “Over” represents how much the limit is exceeded, which is the result of the measured value minus the limit. The calculation formula for the measured value is as follows: Measured Value = Reading Value + Correction Factor. CF = AF + CL - AG. Wherein, AF represents the antenna correction factor, CL represents the coaxial signal cable attenuation loss, and AG represents the signal amplifier gain. A negative Over indicates that the limit is not exceeded, that is, it meets the requirements of the test standard.

[0046] C. Experimental Design

[0047] This trial was a double-blind trial, meaning that neither the subjects nor the optometrists responsible for the test knew whether the clips attached to the glasses worn by the subjects had radio frequency functionality.

[0048] Hereinafter, the 32 eligible subjects underwent bilateral retinal angiography to measure the VD value (i.e., experimental data) at week 0 (i.e., day 0). Subsequently, the experimenters attached eyeglass clips without the radio frequency circuit 11 to the right temple of each subject (i.e., as the control group) and eyeglass clips with the radio frequency circuit 11 to the left temple of each subject (i.e., as the experimental group). The two types of eyeglass clips were identical in appearance. Herein, both the control group and the experimental group were present on the same person to reduce the influence of factors such as individual physiological conditions and eye use time during statistical analysis.

[0049] In the second week (i.e., day 14) and the fourth week (i.e., day 28) after the eyeglass clips were fitted, each subject returned for a re-examination, and retinal microvascular imaging of both eyes was performed again using the same instrument to measure the VD values ​​(i.e., experimental data) in the second and fourth weeks. The re-examination date was limited to + / - 2 days; if it exceeded this period, the experimental data was excluded. After the VD value measurement in the fourth week was completed, the eyeglass clips were collected and stored according to the left and right sides, and brought back to the laboratory to test whether the radiofrequency function of the eyeglass clips collected from the experimental group was normal. If the radiofrequency function was abnormal, the experimental data of this experimental group was excluded. After organizing the experimental data according to the exclusion criteria, the following five items were statistically analyzed using the remaining experimental data: (1) VD value change; (2) VD value change trend over time; (3) the effect of age on VD value change; (4) the effect of disease on VD value change; and (5) response rate analysis.

[0050] Since the left and right eyes of the same person are not anatomically and functionally paired and differ from each other, the experimental data for each eye should be considered as independent observations. Therefore, the experimental data were statistically analyzed using an unpaired t-test, and the statistically derived data are expressed as the mean and the standard error of the mean (i.e., Mean ± SEM). Furthermore, the trend of VD values ​​over time and the analysis of response rates were further statistically analyzed using Repeated Measures ANOVA to obtain the F-value (statistical value).

[0051] In the graph, "*" represents P < 0.05, "**" represents P < 0.01, and "***" represents P < 0.001, all of which indicate statistically significant differences among multiple groups of data. "ns" represents P > 0.05, indicating that there are no statistically significant differences among multiple groups of data.

[0052] Measuring and Analysis Methods for D and VD Values

[0053] Hereinafter, an ophthalmic optical coherence tomography instrument (Avanti RTVue XR High Definition SD-OCT: Angio-OCT) was used to examine and calculate the VD value of the retina of each subject.

[0054] The optical coherence tomography (OCTA) technology of this instrument can perform retinal angiography in a non-invasive manner. The captured image IM is then divided into four eye areas (A1-A4) – upper, right, lower, and left (as shown in Figure 8), and the vascular density of each eye area (A1 / A2 / A3 / A4) is quantified to obtain its VD value. Normally, experimental data from a total of eight eye areas (A1-A4) can be obtained for each subject's eyes.

[0055] In the statistical analysis, considering the dynamic changes in vascular bed density and future clinical applications, in addition to conducting a total VD analysis, the experimental data were further divided into three groups based on VD values: low-density regions (VD value ≤ 39), medium-density regions (40 ≤ VD value ≤ 49), and high-density regions (VD value ≥ 50) for individual statistical analysis. This was to better reflect the different physiological differences in various ocular regions A1 to A4 and to assess the impact of non-thermal radiofrequency microwave EF on different microvascular density regions. Among them, the low-density region (VD value ≤ 39) represents an ocular region that may have small-scale local ischemia, the medium-density region (40 ≤ VD value ≤ 49) represents an ocular region that may have small-scale local ischemia, and the high-density region (VD value ≥ 50) represents an ocular region that clearly does not have local ischemia.

[0056] E. Experimental Results

[0057] A total of 39 subjects were recruited for this trial. Five subjects failed the time test, and two experienced malfunction of the radiofrequency circuit 11. These seven subjects were excluded, leaving 32 subjects whose results were included in the analysis. Furthermore, among the final 32 subjects, one subject had abnormal imaging in their right eye at week 4, suspected to be due to vascular inflammation and congestion, and was referred to a physician. Two other subjects had image deviation in their right eye, resulting in the loss of data for one ocular region, possibly due to visual deviation during the test. In other words, the right eyes of these three subjects met the exclusion criteria, and their right eye data were excluded, but their left eye data were still included in the analysis. The final number of experimental data included in the analysis is shown in Table 2.

[0058] Table 2 Number of eye areas A1~A4 Global VD value ≤ 39 40 ≤ VD value ≤ 49 VD value ≥ 50 control group 116 twenty one 67 28 18% 58% twenty four% experimental group 128 49 60 19 38% 47% 15%

[0059] (1) VD value change

[0060] Hereinafter, the VD value change of each group is calculated using the following formula 1.

[0061] VD value change = VD value in week 4 - VD value in week 0 Equation 1

[0062] Referring to Figure 9A, looking at the entire region, the mean and standard deviation of the VD value changes in the experimental group and the control group were 1.919 ± 0.6928, and there was a significant difference between the two (P = 0.006). Further observation of different microvascular density regions, referring to Figures 9B to 9D, reveals that the significant change in VD values ​​between week 0 and week 4 occurred in the low-density region with VD values ​​≤ 39. Looking at the low-density region (VD value ≤ 39), the mean and standard deviation of the VD value changes in the experimental group and the control group were 3.50 ± 1.467, and there was a significant difference between the two groups (i.e., P = 0.0197), as shown in Figure 9B. In the medium-density region (40 ≤ VD value ≤ 49), the mean and standard deviation of the VD value changes in the experimental and control groups were 0.1565 ± 0.7862, and there was no significant difference between the two groups (i.e., P = 0.8426), as shown in Figure 9C. In the high-density region (VD value ≥ 50), the mean and standard deviation of the VD value changes in the experimental and control groups were 0.1565 ± 0.7862, and there was no significant difference between the two groups (i.e., P = 0.8426), as shown in Figure 9D.

[0063] Therefore, it can be seen that radiofrequency microwave EF has the effect of increasing vascular density (VD), meaning that the non-thermal effect induced by radiofrequency microwave EF can increase vascular density. Moreover, the effect of radiofrequency microwave EF is not significant in areas with high vascular density, and the initial VD value obviously affects the effect of radiofrequency microwave EF. In other words, the non-thermal effect of radiofrequency microwave EF can increase vascular density in areas with low vascular density without causing an abnormal increase in vascular density in normal areas.

[0064] (2)The changing trend of VD value over time

[0065] Looking at the overall picture, the VD value of the control group did not change significantly from week 0 to week 4, as shown in Figure 10A; however, the VD value of the experimental group showed an upward trend and was significant from week 0 to week 4, as shown in Figure 10B. Further observation of different microvascular density regions revealed that the VD value of the control group in the low-density region (VD value ≤ 39) also did not change significantly from week 0 to week 4 and remained relatively stable, as shown in Figure 11A. In contrast, the VD value of the experimental group in the low-density region (VD value ≤ 39) showed an upward trend and was significant from week 0 to week 4, as shown in Figure 11B. In the low-density region (VD value ≤ 39), referring to Figure 11B, the mean and standard deviation of the VD value of the experimental group increased from 34.12 ± 0.557 in week 0 to 37.22 ± 0.808 in week 2, and further increased to 39.39 ± 0.932 in week 4.

[0066] In the medium-density region (40 ≤ VD value ≤ 49), referring to Figures 12A-12B, the F-value of the VD value in the control group from week 0 to week 4 was 1.082 and the P-value was 0.3405, while the F-value of the VD value in the experimental group from week 0 to week 4 was 2.576 and the P-value was 0.0869. That is to say, from week 0 to week 4, there was no significant difference between the experimental group and the control group in the medium-density region, that is, the VD value change curves were basically the same.

[0067] In the high-density region (VD value ≥ 50), referring to Figures 13A and 13B, the F-value of the VD value in the control group from week 0 to week 4 was 8.955 and the P-value was 0.0019, while the F-value of the VD value in the experimental group from week 0 to week 4 was 2.576 and the P-value was 0.0869. Furthermore, from Figures 13A and 13B, it can be seen that the mean and standard deviation of the difference in VD value between week 0 and week 2 in the experimental group in the high-density region was -2.714 ± 1.246, and the P-value was 0.0372 compared to the control group. In other words, the experimental group in the high-density region reacted to the decreasing trend of VD value more quickly, but the final result was the same as the control group (i.e., the VD value in week 4 was similar).

[0068] It can be seen that the non-thermal radio frequency microwave EF not only has the effect of increasing the vascular density in areas with low vascular density without causing an abnormal increase in vascular density in normal areas, but also has the effect of promoting the restoration of vascular density in areas with slightly high microvascular density to the vascular density in normal areas.

[0069] (3)The impact of disease on VD value changes

[0070] Regarding the impact of the disease, in addition to observing experimental data from 6 diabetic patients among the 32 eligible subjects, experimental data from non-diabetic patients and diabetic patients in low-density areas (VD value ≤ 39) were also compared.

[0071] Referring to Figure 14A, in the diabetic population, the mean and standard deviation of VD value changes in control group 1 (n=16) were 1.625±0.6884, while the mean and standard deviation of VD value changes in experimental group 1 (n=24) were 3.792±0.6197. Referring to Figure 14B, in the low-density region (VD value ≤39), the mean and standard deviation of VD value changes in control group 2 (n=21) of the non-diabetic population were 1.762±1.039, the mean and standard deviation of VD value changes in experimental group 2 (n=16) of the diabetic population were 4.75±0.8036, and the mean and standard deviation of VD value changes in experimental group 3 (n=33) of the non-diabetic population were 5.515±1.206. Here, n is the sample size, i.e., the number of ocular regions A1~A4.

[0072] Hereinafter, in the group with diabetes, the mean and standard deviation of the difference between the VD value change in experimental group 1 and the VD value change in control group 1 was 1.925 ± 1.004, and the P value was 0.0275. In the low-density region (VD value ≤ 39), the mean and standard deviation of the difference between the VD value change in experimental group 2 and the VD value change in control group 2 was 2.988 ± 1.384, and the P value was 0.0378. Furthermore, in the low-density region (VD value ≤ 39), the mean and standard deviation of the difference between the VD value change in experimental group 2 and the VD value change in experimental group 3 was 0.7652 ± 1.827, and the P value was 0.6773.

[0073] It can be seen that diabetes does not seem to limit the effects of non-thermal radiofrequency microwave EF.

[0074] (4) Reaction rate analysis

[0075] In the response rate analysis, the VD value of the subjects was statistically analyzed to determine whether it increased, remained the same or decreased, and the results of the statistical analysis are shown in Table 3, Figure 15A and Figure 15B.

[0076] Table 3 group Sample size VD value increases VD value maintained VD value decreases VD value ≤ 39 49 40 4 5 81.6% 8.2% 10.2% 40 ≤ VD value ≤ 49 60 28 9 twenty three 46.7% 15.0% 38.3% VD value ≥ 50 19 1 6 12 5.3% 31.6% 63.2% *The data for each group is presented as the sample size (top) and its percentage within its respective group (bottom).

[0077] Statistical analysis results show that, referring to Table 3, in the low-density region (VD value ≤ 39) with low initial VD values, radio frequency microwave EF significantly increased VD values. 81.6% of individuals experienced an increase in VD value, 10.2% experienced a decrease, and 8.2% remained unchanged. In the medium-density region (40 ≤ VD value ≤ 49), 46.7% of individuals experienced an increase in VD value, 38.3% experienced a decrease, and 15.0% remained unchanged. In the high-density region (VD value ≥ 50), only 5.3% of individuals experienced an increase in VD value, while 63.2% experienced a decrease, and 31.6% remained stable.

[0078] Referring to Figures 15A and 15B, in the control group, the mean and standard deviation of VD value changes for the three groups (VD ≤ 39, 40 ≤ VD ≤ 49, and VD ≥ 50) were 1.76 ± 1.04, -0.37 ± 0.54, and -2.39 ± 0.73, respectively. In the experimental group, the mean and standard deviation of VD value changes for the three groups (VD ≤ 39, 40 ≤ VD ≤ 49, and VD ≥ 50) were 5.27 ± 0.85, -0.22 ± 0.58, and -3.16 ± 1.30, respectively. It was also found that the differences in VD value changes among different microvessel densities in the control group were small (F = 5.548 and P = 0.005), as shown in Figure 15A. In contrast, the VD value changes in the experimental group showed significant differences between different microvascular densities (F=23.25 and P<0.0001), as shown in Figure 15B.

[0079] As shown in the above experiments, the effective range of non-thermal radiofrequency microwave EF is selective to the initial vascular density (VD), increasing low VD values ​​and decreasing high VD values, achieving bidirectional regulation of retinal vascular density. In particular, the non-thermal effect of radiofrequency microwave EF can effectively increase the VD value of the retina, even in diabetic patients, without causing an abnormal increase in vascular density in normal areas. Especially in ocular regions with low vascular density (e.g., VD value ≤ 39), the effect of non-thermal radiofrequency microwave EF can more significantly induce an improvement in vascular density. That is, the non-thermal effect of radiofrequency microwave EF can induce a protective mechanism against vascular endothelial cells and promote more active cooperation of the vascular network with physiological regulation, thereby increasing the VD value in low VD ocular regions. Furthermore, for subjects with longer exposure times to radiofrequency microwave EF, the effect of non-thermal radiofrequency microwave EF can also more significantly improve retinal vascular density.

[0080] In summary, the method for promoting retinal blood circulation using radio frequency microwaves EF, the radio frequency transmitting device 10 using the method, and its application in any embodiment can apply a non-thermal effect to the eye 20 by transmitting radio frequency microwaves EF with a frequency between 30MHz and 1000MHz, thereby substantially imperceptibly adjusting retinal vascular density and improving blood circulation. Specifically, in some embodiments, the method for promoting retinal blood circulation using radio frequency microwaves EF, the radio frequency transmitting device 10 using the method, and its application can increase excessively low vascular density and decrease excessively high vascular density, thereby optimizing the blood flow distribution of retinal microvessels and promoting blood circulation. [Simplified Explanation of the Diagram]

[0081] Figure 1 is a functional block diagram of an embodiment of the radio frequency transmitting device. Figure 2 is a schematic diagram of the appearance of an exemplary example of the radio frequency transmitting device of Figure 1. Figure 3 is an exploded view of the radio frequency transmitting device of Figure 2. Figure 4 is a schematic diagram of the appearance of another exemplary example of the radio frequency transmitting device of Figure 1. Figure 5 is a circuit diagram of an exemplary example of the radio frequency transmitting device of Figure 1. Figure 6 is a functional block diagram of another embodiment of the radio frequency transmitting device. Figure 7 shows the detection results of electromagnetic radiation (Radiated Emission) of the radio frequency transmitting device of Figure 5. Figure 8 is a schematic diagram of an exemplary example of retinal angiography. Figures 9A-9D are bar charts of experimental data on VD value variation. Figures 10A and 10B are graphs of experimental data on VD value variation over time over the entire region. Figures 11A and 11B are graphs of experimental data on VD value variation over time over a low-density region. Figures 12A and 12B are graphs of experimental data on VD value variation over time over a medium-density region. Figures 13A and 13B are curves showing the time-dependent changes in VD values ​​in high-density regions. Figures 14A and 14B are bar charts showing the effects of disease on VD value changes. Figures 15A and 15B are distribution charts showing the experimental data for response rate analysis.

Claims

1. A method for regulating retinal vessel density using radio frequency microwaves to promote blood circulation, comprising: Positioning a radio frequency (RF) transmitter within a range of 3 to 10 centimeters from an eye; driving the RF transmitter to emit an RF microwave at a frequency between 600 MHz and 1000 MHz; and applying a non-thermal effect to the retinal region of the eye using the RF microwave.

2. The method as described in claim 1, wherein the radio frequency transmitting device is a passive radio frequency circuit.

3. The method as described in claim 1, wherein the radio frequency transmitting device is an active radio frequency circuit.

4. The method as described in claim 1, wherein the radio frequency transmitting device is an eyeglass clip or a pair of glasses.

5. The use of a radio frequency transmitting device for modulating retinal vascular density to promote blood circulation, wherein the radio frequency transmitting device is positioned within a range of 3 cm to 10 cm from an eye and is used to apply a radio frequency microwave with a frequency between 600 MHz and 1000 MHz in a non-contact manner.

6. A radio frequency transmitting device for adjusting retinal vessel density, comprising: One launch module; And a control module connected to the transmitting module, configured to generate a radio frequency microwave with a frequency between 600MHz and 1000MHz via the transmitting module.

7. The radio frequency transmitting device as claimed in claim 6, wherein the control module is a passive chip.

8. The radio frequency transmitting apparatus as described in claim 6, further comprising: A power supply module is connected to the control module and configured to supply power to the control module.

9. The radio frequency transmitting apparatus as claimed in claim 6, further comprising: A pair of glasses, and the transmitting module and the control module are mounted on the glasses.

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