device

Abstract

A method for directing light to one or more eyes (300) of a user is disclosed, the method including locating (110) an optic disc (330) on a retina (320) of one or more eyes (300) and selectively directing (115) light to the optic disc (330) to stimulate the optic disc (330). [Selected Figure] Figure 1

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to Luxembourg Patent Application No. 100280 and German Patent Application No. 10 2017 112 694.5, both filed on June 8, 2017. The disclosures of these applications are incorporated herein by reference in their entireties.

[0002] The present invention relates to a system and method for stimulating the optic nerve.

Background Art

[0003] The 24 - hour light - dark (LD) cycle is a fundamental characteristic of the terrestrial environment, and thus it is not surprising that the influence of this LD cycle on the behavior and physiology of animals and humans is significant. Most of the biochemical, physiological, and behavioral variability in humans fluctuates on such a periodic basis, which is referred to as the "circadian rhythm." This circadian timing system enables the body to predict the onset of dawn and dusk and accordingly adjust the body's physiological and behavioral systems. It is currently recognized that these diurnal rhythms are temporally organized by a circadian clock that maintains temporal synchronization between the body and the external environment, similar to the internal coordination of various physiological processes over time.

[0004] The LD cycle is a major environmental factor that synchronizes the body's circadian clock. The ability of the natural LD cycle to synchronize the circadian rhythm is based on the circadian clock's response to light.

[0005] Our eyes are the most common input to such light-dark entraining factor signals for synchronizing the LD cycle with the body's circadian rhythm. The light received by the retina is further processed by the brain to synchronize the circadian rhythm. In mammals, a neural pathway called the retinohypothalamic tract (RHT) directly transmits information about the light-dark environment from the retina to the suprachiasmatic nucleus (SCN). The SCN is a group of cells in the hypothalamus that receives the transmitted light-dark entraining factor signal indicating the transition from light to dark from retinal ganglion cells (RGCs) via the RHT, and distributes the light-dark entraining factor signal to various systems of the body via endocrine glands and neural pathways, ensuring that various systems maintain synchronization between day and night. When these pathways are inhibited, the body's rest-activity cycle is not synchronized with the LD cycle.

[0006] It is known that a phase-shifted light cue can sometimes disrupt the normal circadian rhythm. For example, light exposure at a late time of the biological day, around dusk, will delay the start of activity in nocturnal animals and delay the start of inactivity in diurnal animals. Light exposure at an early time of the biological day (dawn) will advance the start of activity in diurnal species and advance the start of sleep in nocturnal species. This phase-shifting effect of light is clearly a non-imaging effect of light that depends on the circadian phase and plays an important role in the temporal organization of behavior in animals including humans (Dijk & Archer, “Light, Sleep, and Circadian Rhythms: Together Again”, PLOS Biology, vol. 7, issue 6, el000145, June 2009).

[0007] If the light reaching the eyes is out of phase or unwanted artificial light that disrupts the natural LD cycle, many physiological functions of the body are affected. In such cases, light therapy has been shown to be effective in readjusting the LD cycle. Light therapy (also called phototherapy) consists of exposing to light, sunlight or artificial light with a specific spectrum and / or a specific light brightness for a predetermined amount of time, sometimes at a specific time of day.

[0008] Originally, scientists had the implicit belief that the effect of light on the circadian rhythm, like other non-image-forming effects, was mediated by classical photoreceptors that mediate vision. When non-image-forming responses were demonstrated in mice lacking known photoreceptors at that time, this view was shattered. Light still induced a circadian phase-shift response and suppressed the hormone melatonin. Melatonin is the main hormone of the pineal gland and mediates many biological functions controlled by the duration of light and darkness, especially the timing of their physiological functions. The suppression of light-induced melatonin has previously been shown to remain in some visually impaired individuals. These data, along with the demonstration that the spectral sensitivity of non-image-forming responses in humans also differed from visual responses, were consistent with the existence of a novel photoreceptor system, which was subsequently identified as melanopsin.

[0009] The photosensitive pigment melanopsin is expressed in the inner retina of humans and other animals, particularly within a subclass of ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is most sensitive to blue light but is also sensitive to other wavelengths of light in the visible spectrum. This non-visual light response is essential for circadian entrainment in many non-visual functions. These non-visual functions include sleep / wake state (melatonin synthesis), the pupillary light reflex, cognitive ability, mood, spontaneous movement, memory, body temperature, and so on. By indirectly inputting to ipRGCs via the SCN, the light-sensitive suppression of melatonin production in the pineal gland is regulated. In mice lacking the gene Opn4 that encodes melanopsin, the phase-shift in response to light, pupil constriction, and the rapid suppression of activity are all attenuated. Similar to the Opn4 gene, eliminating rods and cones abolishes all well-known image-forming and non-image-forming effects, demonstrating that both the classical photoreceptor system and the novel photoreceptor system contribute to these responses.

[0010] The human eye can see wavelengths in the range of approximately 380 nm to approximately 780 nm. Within this visible light spectrum, while certain wavelengths may cause acute or cumulative light damage to the eye, other wavelengths are required to synchronize the human body rhythm. Historically, phototherapy has been applied through ambient light and / or dedicated task light through the eye. Providing treatment with a conventional lighting system does not distinguish or separate the visual effect of the provided light (e.g., the image-forming function of the light) from the non-visual effect of the provided light (e.g., the non-image-forming function that controls the circadian rhythm). This is because all the generated light is perceived by the eye.

[0011] Many patent documents are known that describe the use of phototherapy and devices used for this therapy. For example, International Publication No. 2016 / 162554 (A1) pamphlet discloses a head-mounted display device that emits light to the eye through a waveguide claimed to be useful for treating light-related disorders. This display device has a controller module that adjusts the wavelength of the light emitted to the eye according to the wavelength that is most effective for ipRGC. However, this device does not include a method for distinguishing between non-image-forming receptors and image-forming photoreceptors in the eye.

[0012] International Publication No. 2010 / 076706 (A1) pamphlet teaches a more specific approach for subjecting a subject to phototherapy, but the disclosed method is limited to a special time frame in the LD cycle, such as during sleep or immediately before falling asleep. Therefore, the disclosed embodiment takes the form of a sleep mask.

[0013] International Publication No. 2014 / 172641 (Iridex) teaches applying a series of short light pulses to the eye tissue at multiple target positions during retinal surgery with a delay in the heat relaxation time to limit the temperature rise of the target eye tissue. This patent application does not teach the use of a system for targeting the optic disk.

[0014] U.S. Patent Application Publication No. 5923398(A) discloses a more practical approach by introducing treatment of peripheral light with an interactive light field for non-visual stimuli, taking advantage of the fact that the peripheral retina is not very involved in conscious vision and thus does not significantly worsen orthophoria. However, despite its complex design, the device taught in this patent document does not completely eliminate the stimulation of visual formation receptors in the eye (rods and cones (cons) are still struck by off-axis photon stimulation).

[0015] Devices and methods for treating the human visual system are known from U.S. Patent Application Publication No. 2007 / 0182928 (assigned to Sabel, Novavision). This method includes the steps of finding and defining a blind zone of deteriorated vision in the human visual system, defining a therapy area that is dominantly located within the blind zone, and subsequently treating the human visual system by presenting visual stimuli to the human visual system. The visual stimuli are presented, for example, on a computer screen. It should be noted that the term "blind zone" used in this patent application should not be regarded as equivalent to the terms "blind spot" or "optic disk", and this method does not include selectively shining light on the blind spot.

[0016] And International Publication No. 2016 / 145064(A1) discloses a system and method for controlling lighting for an individual's circadian function using eyewear, but this patent document does not teach a method for eliminating the interference between phototherapy and normal daily conscious vision. SUMMARY OF THE INVENTION

[0017] The present disclosure teaches an apparatus, a system, and a method for stimulating the optic nerve. The apparatus includes one or more light sources and an optical system for delivering and / or refracting light from the one or more light sources to the optic nerve head.

[0018] A system comprising the apparatus further includes a processor for controlling the temporal and spatial patterns of stimulation, as well as the wavelength and intensity of the light, based on a predefined or personalized algorithm and input from sensors that collect data from external and / or physiological parameters, and an adjustable wearable frame for accommodating the system of light rays and calibration for directing them onto a target area of the retina.

[0019] The method enables the stimulation of intrinsically photosensitive retinal ganglion cells (ipRGCs) by directly irradiating light onto the optic nerve head where the melanopsin-containing axons of the ipRGCs converge.

[0020] The present apparatus and method enable a treatment that has no pharmacological intervention / side effects, does not interfere with the natural visual function of the eye, is a stimulation of invisible light, is not harmful to the image-forming area of the retina, and does not impair the user's attention and perceptual ability.

[0021] In one aspect of the present disclosure, a method for applying light to one or more eyes of a user is described. The method includes identifying the position of the optic nerve head on the retina of the one or more eyes and selectively applying light to the optic nerve head to stimulate it. By selectively applying light to the optic nerve head, it becomes possible to stimulate the optic nerve head with intense light without damaging other parts of the retina.

[0022] The light is selected to have a wavelength in the range of 360 to 540 nm. In another aspect of the present invention, the light is selected to have a wavelength in the range of 480 + / - 40 nm.

[0023] Specifying includes at least one of exposing the user to stimulating light applied to one or more eyes of the retina, monitoring that the stimulating light has been perceived, or mapping the retina.

[0024] There are various ways to generate light. These include, but are not limited to, one of an LED source, a laser emitter, or a display device.

[0025] The method may also include restricting at least one visual field of an eye. This is designed to ensure that the user moves their eyes without distraction and thus that the light does not affect other parts of the retina.

[0026] The method may additionally include monitoring at least one of the position of the pupil of one or more eyes (300), or the direction of the visual field of one or more eyes. This enables the light to be switched off if it is determined that the light is no longer directed towards the optic nerve head.

[0027] The method may further include adapting the composition of the light. This adaptation is useful for adapting the light to the user.

[0028] The method has many applications such as the treatment of myopia.

[0029] The present disclosure also teaches a device for implementing the method. The device comprises a light source for emitting light, an identifier for identifying the position of the optic nerve head on the retina of one or more eyes, and an optical system configured to selectively apply the emitted light to the optic nerve head. A controller may be provided to control the device. For example, the controller adapts the optical system and / or the composition of the light.

[0030] The identifier may be, for example, a device for mapping the retina of one or more eyes.

[0031] In an aspect of the present disclosure, the device further comprises an eye tracking system, an electrooculography system, or an electroretinography system for monitoring at least one of the positions of the pupils of one or more eyes or the directions of the visual fields of one or more eyes.

[0032] Also, the device may comprise one or more mechanical or electro-optical actuators for changing the position of the light radiation source. These function in conjunction with the eye tracking system to ensure that the light is directed towards the optic nerve head. Similarly, the device may further provide for the optical system to adapt to at least one of the positions of the pupils of one or more eyes or the direction of the visual field of one of the one or more eyes.

[0033] In a further aspect of the invention, the optical system may be further configured to selectively direct the emitted light to other parts of the eye. This emitted light may have the same combination of light or a different combination of light different from the light hitting the optic nerve head.

Brief Description of the Drawings

[0034]

Figure 1

Figure 2

Figure 3

Modes for Carrying Out the Invention

[0035] The schematic of a method of phototherapy by stimulating the optic nerve of mammals such as humans without impairing orthovision is shown in FIG. 1. The devices and systems used to carry out the method are shown in FIG. 2.

[0036] Figure 3 shows an example of an eye, focusing on the biological characteristics of the eye 300. The eye 300 has an eyeball 310 with a retina 320 in which a blind spot 330 or optic nerve papilla is located. The retina 330 is connected to an optic nerve 340 that transmits signals formed on the retina 320 to the brain. The optic nerve papilla 330 is a raised disc on the retina 320 at the entrance point of the optic nerve 340, without visual receptors, thus causing a blind spot.

[0037] In step 100, a light source is selected and set. The light source setting step 100 is a process of selecting the optimal wavelength, intensity, temporal and spatial patterns of light stimulation via a controller device based on internal parameters of the user's body or external parameters of the surroundings. The light source setting step 100 can be a process of selecting a set of predefined parameters or individualized parameters, or selecting light characteristics according to ambient light, time, etc. The light source setting step 100 can be based on an artificial intelligence algorithm or can use a computational model of the eye 300 and / or the body.

[0038] In step 110, for example, the blind spot of the eye is identified by irradiating the optic nerve papilla 330 of the eye 300 with the selected wavelength or another visible light wavelength. The purpose of this step is to ensure that non-image-forming light is delivered to the optic nerve papilla 330 of the retina 320 of the eye 300. The identification of the position of the blind spot is based on the geometric characteristics of the eye and the subjective reports of the user. Closed-loop control of the non-visible light therapy is performed by an electrooculogram recording system or by monitoring the pupil. The identification of the position of the blind spot can be automatic, semi-automatic, or manual, and is performed by the device or by the user. In another aspect of the method, the optic nerve papilla 330 is identified by mapping the retina 320. This mapping can be done automatically or by an ophthalmologist.

[0039] Examples of systems that enable the identification of the optic nerve papilla 330 by mapping the retina 320 include video-based imaging systems, eye tracking systems, pupillometers, fundus imaging, retinoscopes, and ophthalmoscopes.

[0040] In step 115, light is irradiated onto the optic nerve head, and melanopsin stimulation is performed in step 120. The axons of ipRGCs present in the optic nerve head are stimulated by light. ipRGCs are a subset of retinal ganglion cells that exclusively express melanopsin, a photosensitive pigment for non-image-forming visual functions such as circadian rhythm synchronization. This method aims to stimulate the axons that form the optic nerves of all ipRGCs in the retina of the optic nerve head. In step 130, by stimulating the axons / ganglion cells expressing melanopsin, the release of retinal dopamine is stimulated. The release of dopamine by light synchronizes the LD cycle with the master clock of the circadian rhythm in the SCN in the brain in step 140.

[0041] FIG. 2 shows an example of device 1 used in the present disclosure. It should be understood that the illustrated device 1 is only a non-limiting example. Device 1 comprises substantially a pair of spectacles or eyeglasses including a spectacle frame 24, a bridge 26 and two lenses 25. Device 1 is connected to a computer 42 and a controller 40 by a cable 44 (or via a wireless connection). The controller 40 can be mounted on the spectacle frame 42 or can be a separate unit.

[0042] The lenses 25 have electrodes for an electrooculogram or electroretinogram examination system. These are shown as the vertical electrodes 11 of the left lens 25, the horizontal electrodes 15 of both lenses 25, and the reference electrode 14 of the bridge 26. It will be understood that only a pair of vertical electrodes 11 are required because the eyes 300 move horizontally. Element 13 represents various sensors also mounted on the bridge 26. These sensors include, but are not limited to, environmental sensors, light sensors, time-of-flight cameras (ToF), distance sensors, temperature sensors, cameras, and the like.

[0043] The lens 25 has an eye tracking system 10 mounted thereon, which determines the position of the pupil and the direction of the field of view. Each of the lenses has a light emission source 34, which can be, for example, an LED, a laser beam, or a projection / generation on a display. The light from the LED can be blue or another color, or a mixture of colors. The mixture can be generated continuously as a sequential RGB system of colors, or the mixtures can be combined simultaneously.

[0044] The light emission source 34 can be separate from the glasses 1. Non-limiting examples of other light emission sources 34 include digital light processing, laser beam steering, liquid crystal on silicon (LCoS), microscanners, virtual retinal displays, EyeTap devices, micro or picoprojectors, holography, or light fields. These light emission sources can be incorporated as light sources that can be embedded in a head-up display (HUD), an optical head-mounted display (OHMD), or further in the eye or on the optic disc.

[0045] As will be described later, the optical system 7 directs light from the light emission source 34 to the optic disc 330 of the eye 300. The optical system 7 includes, for example, a waveguide and may include other elements. In this example, the optical system 7 is mounted on a rail that is driven by a motor to move the position of the light emission source 34 if necessary. It will be understood that the optical system 7 and the rail 16 enable light to be directed from the light emission source 34 into the eye 300 and can be easily adjusted for different users. Further examples of the optical system 7 include, but are not limited to, diffraction devices, prisms, holographic devices, polarization devices, beam splitting devices, clear-vu devices, switchable devices, or mirror devices. Examples of mirror devices include pin mirrors or one-sided mirrors. It is also possible to use combined devices, such as a birdbath device having a beam splitter with a light combiner.

[0046] The body sensor 17 is also attached to the spectacle frame 24. The role of the body sensor 17 is to measure parameters regarding temperature, heart rate, and other physical parameters of the user. This information is transmitted to and processed by the controller 40.

[0047] Recent research has shown that the pupillary light reflex is enhanced by light projected within the blind spot 330 of the human eye 300 (Miyamoto and Mirakami, “Pupillary light reflex to light insider of the natural blind spot”, Scientific Reports, 5: 11862, DOI: 20.1038 / srepl 1862, June 2015). This has proven that the photosensitive pigment melanopsin exists in the optic nerve head 330 where no other visual photoreceptors are present. It is known that ipRGCs mediate light-sensitive pupillary constriction by connecting to the pretectal olivary nucleus (Dijk and Archer, “Light, Sleep and Circadian Rhythms: Together Again”, PLOS Biology, Vol7, issue 6, el000145, June 2009).

[0048] There are no image-forming receptors in the optic nerve head 330. Therefore, projecting light onto the optic nerve head 330 does not cause deterioration of eyesight, flickering or glare, and obvious and hidden attentional and perceptual disorders in visual processing.

[0049] Since simply stimulating the optic nerve head 330 is not sufficient to cause pupillary constriction, projecting light onto the optic nerve head 330 does not result in unwanted pupillary constriction (Miyamoto and Murakami, 2015).

[0050] On the other hand, in conventional whole-eye phototherapy for the entire eye 300 that is not limited to simply the projection of light onto the optic nerve head 330, the photoreceptors in the retina 320 are non-selectively stimulated. This conventional whole-eye phototherapy has unknown effects on higher-order cortical processes via retinal circuits and / or the image formation pathway, thereby causing conscious information processing disorders, and / or mental or emotional side effects such as sleep disorders, stress, depression or anxiety, similar to brain dysfunctions such as seizures and epilepsy.

[0051] To perform optimal phototherapy, when using phototherapy on a patient, several stimulation parameters should be taken into account. These stimulation parameters include, but are not limited to, the temporal pattern of light, the spatial pattern of light, intensity, duration, wavelength of light, etc. It is known that the intensity, wavelength, spatial characteristics and temporal pattern of light stimulation in the method described above must be adjusted to reduce the perception of phototherapy by the patient. This is explained, for example, in WO 2016 / 162554 A1 pamphlet.

[0052] By the method of the present disclosure, any light intensity and duration can be delivered to the patient's eye 300 because there are no visual photoreceptors to be damaged in the optic nerve head 330. Moreover, the response profile of ipRGCs is different from other types of photoreceptors (i.e., rods and cones (cons)) in the retina 330. The temporal composition (frequency of light on / off, on / off pattern, etc.) of the stimulating light can be optimized for ipRGCs according to the patient's requirements. Since ipRGCs are the only photoreceptors on the optic nerve head 330 and the other parts of the retina 320 are not irradiated with light, this change is independent of the response profiles of other photoreceptors.

[0053] The previously described stimulation parameters can be adjusted independently of each other to keep the overall parameter intensity below a specific threshold, thereby preventing light from scattering from the optic nerve head 330 to other regions of the retina 320 of the eye 300. These other regions contain image-forming photosensitive pigments and give rise to the visual perception of the stimulating light.

[0054] The melanopsin receptors of the optic nerve head 330 have been found to have optimal sensitivity to distinct blue light wavelengths. Therefore, light of this wavelength should be used to provide an effective phototherapy treatment. Since the delivery of light does not occur via the retina, i.e., rods and cones (cons), safety issues using blue light wavelengths such as blue light hazard are less than those due to conventional phototherapy. As previously mentioned, the optic nerve head 330 does not have rods and cones (cons). During conventional stimulation of the entire eye, blue light, which is part of the visible light spectrum, reaches deeper into the eye 300 and may cause damage to the retina 320 due to its cumulative effect. Furthermore, at specific wavelengths, blue light has been associated with the onset of age-related macular degeneration (AMD).

[0055] This method could be applied to the daily routines of normal life. As described in the preferred embodiment, the radiation source 34 that selectively emits light to the optic nerve head 330 can be housed within the spectacle frame 24 or added to the patient's current spectacle frame 24. To implement this method, no additional complex eyewear such as virtual reality devices, including but not limited to Google glass Microsoft HoloLens, Magic Leap, Intel Vaunt or Oculus Rift, is required. Therefore, the normal visual function of the eye 300 is not impaired and natural foveal vision is maintained. Advantageously, the stimulation can also be applied at night without making the subject feel the light, thereby enabling this method to be applied to people who require phototherapy during the dark period without exposing them to visual light.

[0056] Since the imaging light receptor is not present at the optic nerve head 330, this method does not require an optical filter (such as that proposed in WO 2016 / 162554 A1) or a chromatic filter for filtering the visible spectrum. Moreover, since the position of the optic disc 330 of the retina 320 is constant and the stimulus remains invisible, no spatial adjustment / control is required to change the spatial configuration of the stimulus and keep it from being overly disrupted during phototherapy (as taught in WO 2016 / 162554 A1). A method is provided for retaining the emitted light inside the optic disk 330 with respect to the fixation direction.

[0057] The spatial density of ipRGCs (only 1 - 3% of retinal ganglion cells) is much lower than that of rod photoreceptors. The probability of photon absorption by ipRGCs is more than a million times lower for a given retinal area of light stimulation. Thus, in some prior art methods having an approach of stimulating the entire retina, it is assumed that ipRGCs receive additional input from a complementary photoreceptive process including rods. In other well - known methods, both direct stimulation of ipRGCs by extending the transmitted spectral range up to 460 - 520 nm and indirect stimulation by the incoming rod - driving signal peaking around 500 nm are involved. However, these prior art methods have the problem that the light becomes visible due to rod photoreception. The method described herein specifically stimulates all ipRGCs at the convergence point of the axons of all retinal ganglion cells (RGCs) on the optic nerve head 330 where no other types of receptors are present.

[0058] Melanopsin is the main photoreceptor in the retina 320 that regulates the circadian rhythm. The method of the present disclosure targets melanopsin expressed in the axons of ipRGCs in the optic nerve head 330, among other locations. RGCs that express other types of photoreceptor proteins (e.g., rhodopsin) are not necessary for the circadian system (as demonstrated in the blind). Stimulating RGCs that express non-melanopsin may provide an indirect input to the master circadian clock. Stimulation of the optic nerve head 330 exhibits the greatest specificity when targeting melanopsin, thereby providing the highest level of freedom to a system for adjusting the minimum number of the previously described stimulation parameters for optimal non-visual stimulation.

[0059] The stimulated optic nerve 340 directly transmits the optical signal to the SCN via the RHT, which is a highway to the center of the master circadian clock in the brain. In other words, the system provides intraocular (but non-visual) stimulation instead of a less special route such as ear canal stimulation or other extra-cranial locations (as disclosed in, for example, WO 2015 / 010920A1 pamphlet).

[0060] Stimulation of the optic nerve head 330 is performed via one or an array of light-emitting diodes (LEDs) in the radiation source 34 housed within the eyeglass frame 24, or the like. This enables precise control of the direction of light with respect to the eye 300 by an optical system such as an optical waveguide tube. The optical waveguide tube ensures that the light is exclusively delivered to the optic nerve head 330 on the retina 320.

[0061] In another aspect, the stimulation pattern is applied to the area of the display corresponding to the blind spot in a line-of-sight following manner with respect to the eye by changes in wavelength, luminance, and other parameters of the display (e.g., TV, monitor, screen, virtual reality (VR) goggles (including light field technology that enables light from the display to be incident on multiple focal planes of the eye), augmented reality (AR) goggles, mixed reality (MR) goggles, beamer, Internet of Things (IoT) devices, smart home appliances, smart lighting systems, interior design arrangements, in-vehicle displays, or windshield, etc.). The line-of-sight direction is measured online by an eye tracking system (remote or mobile), and the spatial position of the stimulation pattern changes according to the position of the eye 300. The stimulation pattern can be optimized to deliver a specific wavelength having a specific temporal and spatial pattern. Since the perceptual filling process of the visual system interpolates the lack of visual input at the optic nerve papilla 330, the pattern does not affect the overall perception of visual input from the display. Such an embodiment is ideal for applications when a patient spends working hours in front of a computer monitor or is watching a TV, etc.

[0062] In another aspect, the light source 34 is combined with a myopia control lens as the lens 25 of the eyeglass frame 24. The myopia control lens is a powerful tool for controlling myopia. The myopia control lens provides a large positive correction to the periphery while keeping the central vision clear. The strong blur of peripheral vision helps the patient to keep the eye 300 centered (like a pinhole), resulting in restricted fixation dynamics and helping to maintain the light stimulation within the optic nerve papilla 330.

[0063] In another aspect, the optical waveguide tube is a pinhole that guides light from an LED in the light source 34 of the eyeglass frame 24 and directs it onto the optic nerve head 330. The optic nerve head 330 of the human eye 300 corresponds to a blind spot that is located approximately 15 degrees of visual angle outside the fovea 315 and has a relatively large dimension of 5 to 7 degrees of visual angle. In this embodiment, the fixation dynamics are restricted to ensure that the pinhole keeps the light therapy invisible within the blind spot. In such an embodiment, the user needs to use the eyeglass frame in daily static situations such as working in front of a monitor or watching TV. Since the pinhole does not allow peripheral viewing, excessive eye movements are naturally restricted. Therefore, if necessary, the movement of fixation is converted into head movement. While the user's head moves instead of the eye 300, the position of the optic nerve head 330 remains constant relative to the light source 34.

[0064] The light can be deflected and emitted through a polarizing filter on the eyeglass lens 25. This ensures that the light always reaches the eye 300 perpendicularly. If the light source 34 is positioned and calibrated relative to the position of the optic nerve head 330 according to the position of the patient's eye 300 and the position of the eyeglass frame 24, the light will not reach the photoreceptors of the retina beyond the optic nerve head 330.

[0065] In another aspect, electrodes for electrooculogram (EOG) or electroretinogram are housed within the eyeglass frame 24 and the temple as described above. The EOG transmits a signal of the fixation direction and enables the light source 34 to automatically switch on and off according to the position of the eye 300. When the eye is looking straight at the light source 34, the stimulation pattern hits the optic nerve head 330. When the eye 300 looks away from the center, the pattern switches off so as not to irradiate other light-sensitive parts of the retina 320 (see also U.S. Patent Application Publication No. 2004 / 0070729A1).

[0066] The control system of the light switch and the EOG system takes into account the required temporal characteristics of the stimulus and the frequency limits of the EOG system to ensure the exact switching time of the light source 34 so that the subject does not constantly see light.

[0067] The light source 34 is advantageously housed in the form of glasses 20. To stimulate the optic nerve head 330, the light source 34 can be accurately positioned in a one-time calibration procedure. The calibration has a subjective guide for the patient and makes the test light invisible to the patient by spatially aligning the position and dimensions of the guide on the optic nerve head 330. In another calibration procedure, an eye tracking system, together with a three-dimensional model of the eye 300, measures the fixation direction and the relative position of the optic disk 330 with respect to foveal fixation to first guide the attachment of the light source 34 of the glasses frame 24 to the wearer. In any of the calibration procedures, the relative position of the light source 34 with respect to the center of each eye 300 is adjustable by a freely movable rail system attached to the glasses frame 24.

[0068] In another embodiment, the light source 34 can adaptively change its position and / or direction according to the position of the eye and the fixation direction. In this situation, the eye 300 can be continuously irradiated with light and always kept within the optic nerve head 330. This is useful for the continuous irradiation mode for longer exposure times.

[0069] The controller is configured to provide personalized light therapy to a patient, for example, by a specific emission wavelength in front of the eye 300. Thus, the pattern of the stimulating light can be changed, for example, for epilepsy patients. The controller can parametrically change the temporal pattern, intensity, wavelength, spatial pattern, duration of light, etc. The controller can control the stimulation pattern according to external parameters such as, for example, the ambient light level, time, etc. It can control the stimulation pattern according to internal parameters such as, for example, physiological factors, heart rate, temperature, pupil size, eyelid position, etc. It can control the stimulation pattern according to personalized information such as, for example, age, size, gender, etc. The controller is housed in the body and the temples of the spectacle frame 24.

[0070] Similar to the retina, melanopsin signaling is also known to occur in the iris (Xuc et al, "Melanopsin signaling in mammalian iris and retina”, Nature, vol. 479, 67 - 73, 3 November 2011, DOI: 10. 1038 nature 10567). The methods and devices herein enable the determination of the position of the pupil and subsequently also the position of the iris. Thus, similar to stimulating the optic nerve head, the iris can be stimulated with a similar or different light composition. Since the iris has no image - forming photoreceptors, stimulating the iris also remains invisible.

[0071] In further aspects of the present method and system, if necessary, in conjunction with the stimulation of the optic nerve head, other parts of the retina can also be irradiated with light. It has been shown that melanopsin receptors exhibit bistable behavior (Mure et al., “Melanopsin Binstability: A Fly′s Eye Technology in the Human Retina”, POS One, vol. 4, issue 4, e5991, June 2009). Therefore, by irradiating the retina with red light, the responsiveness of melanopsin receptors to blue light can be enhanced. Also, the slightly sub-visible intensities of violet and ultraviolet light irradiated onto the retina may have desirable effects, as described in the application examples of the devices described herein, such as myopia.

Example

[0072] Myopia

[0073] The present method and system can be used to prevent and / or reduce myopia. It is known that myopia occurs when the eyeball 310 is too long relative to the ability of the cornea and lens of the eye 300 to focus. This extra length of the eyeball 310 causes light rays to focus at a point in front of the retina 320 rather than directly on the surface of the retina 320. When phototherapy is applied, the risk of myopia development is reduced by actively acting on the production cycle of dopamine. Dopamine is a neurotransmitter of the retina associated with light adaptation. Dopamine affects the length of the eye and thus myopia. Recent research has shown that dopaminergic cells are linked to intrinsically photosensitive retinal ganglion cells and that they are regulated by circa-biological blue light of approximately 480 nm. This specific light is thought to activate the production of endogenous dopamine, while the absence of this light (spectrum and / or light level) may inhibit dopamine production. This inhibition may contribute to eye elongation over time. For details, see Myopia, light and circadian rhythms (Phillips et al, “Myopia, Light and Circadian Rhythms”, Advances in Ophthalmology, Edited by Rumelt, March 2012). Also see the specification of Chinese Patent Application Publication No. 1432348A.

[0074] It has been shown that a broken LD cycle can lead to myopia. It is prevalent in cities where children do not go outside enough and do not experience natural daylight. Recent research has shown that violet light (wavelengths of 360 - 400 nm) can suppress the progression of myopia (Torii et al, “Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression”, EBioMedecine, 15 (2017) 210 - 219), see also the specification of international application PCT / JP2015 / 065997 regarding myopia prevention devices. This part of the light spectrum is always excluded from our advanced industrial countries due to the use of UV protection. However, exposure to short - wavelength light has been the subject of investigation for decades and has been shown to induce photo - oxidation and retinal degeneration (Schaeffel and Smith, “Inhibiting Myopia by (nearly) invisible light”, EBioMedecine, 16 (2017) 27 - 28, DOI: 10.1016 / j. ebiom.2017.01.016). Therefore, short - wavelength stimulation of the optic nerve head 330 is advantageous regarding safety issues. Because the light does not hit the retina 320 and only hits the optic nerve head 330 without rods and cones (cons).

[0075] On the other hand, long - wavelength light (650 nm, red) has been shown to act as a strong inhibitor of eye growth in macaques and tupai, while the opposite has been found in chickens. Research on other wavelengths in myopia investigations mainly includes bright blue - green light that is mainly involved in the endogenous production and regulation of melatonin.

[0076] Further research indicates that green light may be effective during the evening and early biological night under natural conditions, or may be more effective than blue light in certain situations. Additionally, the relative effectiveness of green light decreases over the course of the night and may affect the circadian response during late night and early morning hours, resulting in blue light potentially being relatively more effective than green light. Therefore, in addition to the wavelength of the stimulus, the timing of the stimulus is relevant. The methods and devices of the present disclosure enable independent adjustment of the light wavelength, as well as the intensity, duration, and precise timing of the stimulus, in accordance with endogenous and exogenous biological rhythms. Moreover, flickering light (as opposed to constant light) may be more suitable for dopamine production. Current methods and systems have no constraints regarding the temporal pattern of the stimulus.

[0077] It is also possible to minimize or prevent progressive myopia by combining filtering of light reaching the retina (e.g., filtering of red light) with phototherapy of the blind spot.

[0078] There is also evidence that dopamine produced elsewhere than in the retina 320 can affect the prevention of myopia. L-DOPA is a drug that increases dopamine concentration, and this drug has been shown to inhibit the development of the transition to myopia when the patient is light-deprived. This indicates that increasing dopamine concentration, regardless of whether dopamine is generated by light stimulation through the eye 300, can inhibit the progression of myopia. Therefore, light stimulation of the optic nerve head 330 to produce dopamine can similarly have a beneficial effect on myopia, like L-DOPA, but without the side effects of pharmacological intervention.

[0079] Researchers recommend going out for 2 to 3 hours every day. On the other hand, when light is shown at the wrong time (deviating from synchronization with the circadian rhythm), it may be bad for myopia. To help prevent myopia, children need light therapy that promotes dopamine, but there can be a problem that they cannot be relied upon to receive treatment at the appropriate time or, conversely, not to receive treatment at an inappropriate time. The present method and apparatus enable invisible light therapy through the eyes anywhere and at any time while the patient does not need to control the stimulation and / or timing.

[0080] Sleep

[0081] Under normal conditions, there is a stable phase relationship among the circadian rhythm, sleep, and the light-dark cycle. In animals living under natural conditions, it is rare, if not non-existent, for sleep and the circadian rhythm to deviate from their normal phases with respect to the synchronized light-dark cycle. However, humans routinely disrupt the normal synchronization of the sleep-wake cycle and the light-dark cycle, either in the short term (i.e., following rapid travel across time zones, which is referred to as the "jet lag" syndrome) or in the long term (i.e., as occurs in "shift workers"). The influence of light on the non-image-forming responses in humans depends more on the correlated color temperature (CCT) of the light than on the type of light itself (e.g., incandescent, fluorescent, LED, etc.). To prevent circadian disruption and melatonin suppression, it may be necessary to substantially modify the CCT of the light to which night shift workers are exposed. Although effective in protecting melatonin and other circadian rhythms, completely lacking short-wavelength light may result in reduced contrast and clarity, which, among other deficiencies, presents a safety issue for certain night workers or surgeons, and thus the practicality of these methods may be limited. The present method and apparatus can be used as an alternative to such changes to synchronize the circadian rhythm to its natural cycle. Potential uses include those by shift workers, travelers, individuals exposed to light from artificial sources at times of day-night with respect to their circadian rhythm, and individuals attempting to normalize their circadian rhythm.

[0082] In addition to affecting the perception of visual images, light modulates physiological and behavioral temporal rhythms by sending signals to structures within the brain, including the central circadian clock. These signals are mediated in part by a photosensitive pigment found in the retina called melanopsin. Light affects the brain through these non-visual pathways, and scientists are just beginning to recognize the extent of these non-visual effects in recent years. There is growing evidence to support the view that the effects of light on brain activity during sleep and wakefulness, like the duration of sleep and the homeostatic response to sleep deprivation, depend on both melanopsin and circadian time (Dijk and Archer, 2009). The methods and apparatus of the present invention can be used to enhance sleep disorders and / or jet lag problems, or the health of shift workers, by stimulating dopamine release and melatonin regulation through phototherapy of the optic nerve head.

[0083] Other uses

[0084] The methods and apparatus of this specification can be used in therapies for treating patients suffering from circadian rhythm sleep disorders, sleep disorders, pupillary dilation, sleep phase delay and advance syndromes, mood disorders, seasonal affective disorders such as depression or fatigue, postpartum depression, cancer risk, hormonal disorders, agility disorders and cognitive abilities, appetite and obesity, memory disorders, psychomotor disorders, thermoregulatory disorders, premenstrual disorders, seizure disorders and other chronobiological disorders such as epilepsy. The apparatus and method can be used, for example, in a work environment, to reach an increased level of human agility and ability. The system and method can be used to treat various other disorders such as migraine, anxiety, obsessive-compulsive disorder (OCD), and alcohol and nicotine addiction.

[0085] The method and system according to the present invention can compensate for inappropriate light conditions (lack of beneficial blue light at a specific time point) and help the biological clock maintain a synchronized state through a good blue / melatonin secretion relationship. Circadian rhythms can be observed in various physiological functions, including but not limited to sleep / wake cycles, feeding times, mood, agility, cognitive functions, cell proliferation and gene expression in various tissue types. Various tissues and cell types include, among others, independently oscillating cellular clocks such as the liver, kidney, and pancreas, which can function autonomously through the circadian expression of their "clock genes", but they are usually regulated and synchronized by the central SCN clock.

[0086] Phototherapy effectively regulates the amount of melatonin in the body. Evidence of the anti-tumor effects of melatonin shown in in vitro and animal studies suggests a major role in tumor suppression and protection against the growth of cancer cells, including human breast and prostate cancers. Low levels of nocturnal melatonin release may be associated with breast cancer, prostate cancer, type 2 diabetes, metabolic syndrome, insulin resistance, diabetic retinopathy, macular degeneration, hypertension, coronary artery disease, congestive heart failure, depression, anxiety, migraine, and other life-threatening or debilitating conditions. In recent years, there has been an increasing recognition that melatonin can provide protection from disease and that lower levels of melatonin are associated with a wide variety of diseases and chronic conditions. The scope of this association can potentially be broad and may include, for example, cancers, cardiovascular diseases such as hypertension and coronary artery disease, metabolic disorders such as insulin resistance and type II diabetes, Huntington's disease, multiple sclerosis, Alzheimer's disease, migraine, and mental disorders such as depression and anxiety. In some diseases such as cancer, there appears to be an inverse linear relationship between melatonin levels and disease risk, such that lower melatonin concentrations are associated with a significant increase in disease risk. Furthermore, there is no clear "threshold" indicating that any reduction in endogenous melatonin due to nocturnal light exposure is relatively associated with an increase in disease risk. Therefore, it may be necessary to minimize circadian disruption and protect neuroendocrine rhythms such as melatonin.

[0087] Devices according to the methods disclosed by the present invention can also be used in treatment methods for treating subjects suffering from epilepsy. Recent studies have suggested that epilepsy and some types of depression are bidirectional conditions, suggesting that phototherapy may be an effective treatment for some epileptic patients. The production of endogenous melatonin appears to affect the seizure threshold in patients with temporal lobe epilepsy. In addition, bright blue-green light is mainly involved in the endogenous production and regulation of melatonin. Therefore, it can be hypothesized that bright blue-green light is somewhat involved in the regulation of seizure threshold. For people suffering from lobe temporal epilepsy, light may help to somewhat remove the seasonal peak in the frequency of seizures. The invention disclosed in this specification includes the following aspects. 〔Aspect 1〕 A method for applying light to one or more eyes (300) of a user, identifying (110) the position of the optic nerve head (330) on the retina (320) of the one or more eyes (300), and selectively applying the light to the optic nerve head (330) to stimulate the optic nerve head (330). 〔Aspect 2〕 The method according to Aspect 1, wherein the light is selected to have a wavelength in the range of 360 to 540 nm. 〔Aspect 3〕 The method according to Aspect 1 or 2, wherein the identifying (110) includes at least one of exposing the user to stimulating light applied to the retina (320) of the one or more eyes (300), monitoring the perception of the stimulating light, or mapping the retina (320). 〔Aspect 4〕 The method according to any one of Aspects 1 to 3, wherein the light is emitted from one of an LED source, a laser emitter, or a display device. 〔Aspect 5〕 The method according to any one of Aspects 1 to 4, further comprising restricting at least one visual field of the eye (300). 〔Aspect 6〕 The method according to any one of Aspects 1 to 5, further comprising monitoring at least one of the position of the pupil of the one or more eyes (300) or the direction of the visual field of the one or more eyes (300). 〔Aspect 7〕 The method according to Aspect 6, further comprising adapting the composition of the light. 〔Aspect 8〕 The method according to any one of Aspects 1 to 7, further comprising selectively applying the light to other parts of the one or more eyes (300). 〔Aspect 9〕 Use of the method according to any one of Aspects 1 to 8 for the treatment of myopia. 〔Aspect 10〕 A device for selectively applying light to one or more eyes (300) of a user, a light radiation source (34) for emitting the light, an identifier for identifying the position of the optic nerve head (30) on the retina (320) of the one or more eyes (300), and an optical system adapted to selectively apply the emitted light to the optic nerve head (330). 〔Aspect 11〕 The device according to Aspect 10, further comprising a device for restricting the visual field. 〔Aspect 12〕 The device according to Aspect 10 or 11, wherein the light is selected to have a wavelength in the range of 360 to 540 nm. 〔Aspect 13〕 13. The device of any one of aspects 10 to 12, wherein the identifier comprises a device for mapping the retina (330) of the one or more eyes (300). Aspect 14 14. The device of any one of aspects 10 to 13, wherein the light radiation source (34) is one of an LED source, a laser emitter, or a display device. Aspect 15 15. The device of any one of aspects 10 to 14, further comprising an eye tracking system or an electrogram recording system for monitoring at least one of the position of the pupils of the one or more eyes (300) or the direction of vision of the one or more eyes (300). Aspect 16 16. The device of embodiment 15, wherein the light radiation source (34) is adapted to modify the composition of the light. Aspect 17 A device according to any one of aspects 10 to 16, wherein the optical system further directs the emitted light onto other portions of the one or more eyes (300). Aspect 18 18. The device of any one of aspects 10-17, further comprising one or more actuators for changing the position of the light emitter (34). Aspect 19 19. The device of any one of aspects 10 to 18, wherein the optical system is adapted to at least one of the position of the pupil of the one or more eyes (300) or the direction of field of view of one of the one or more eyes (300).

Description of Symbols

[0088] 1 Device 7 Optical System 10 Eye Tracking System 11 Vertical Electrode 13 Sensor 14 Reference Electrode 15 Horizontal Electrode 16 Rail 17 Body Sensor 24 Eyeglass Frame 25 Lens 26 Bridge 34 Light Emitting Source 40 Controller 42 Computer 44 Cable 300 Eye 310 Eyeball 315 Fovea 320 Retina 330 Blind Spot or Optic Disc 340 Optic nerve

Claims

1. A device for use in selectively applying light to the optic nerve head of one or more eyes (300) of a user, comprising: a) a light source (34) for emitting said light; b) a controller (40) for selecting the emitted light; c) an optical system adapted to selectively apply the emitted light to the optic nerve head (330) without applying the emitted light to the image-forming photoreceptors in the retina, thereby stimulating the melanopsin located in the optic nerve head. A device comprising the above.

2. A device for use in suppressing the progression of myopia in one or more eyes (300) of a user, comprising: a) a light source (34) for emitting light; b) a controller (40) for selecting the emitted light; c) an optical system adapted to selectively apply the emitted light to the optic nerve head (330) without applying the emitted light to the image-forming photoreceptors in the retina, thereby stimulating the melanopsin located in the optic nerve head. The device further comprising: wherein the selective application of light to the optic nerve head stimulates the melanopsin in the optic nerve head and suppresses the progression of myopia in the user.

3. The device according to claim 1 or 2, further comprising a device for restricting the visual field.

4. The device according to any one of claims 1 to 3, wherein the controller (40) is configured to select light having a wavelength in the range of 360 to 540 nm.

5. The device according to any one of claims 1 to 4, further comprising an eye tracking system or an electrical recording system for monitoring at least one of the position of the pupil of the one or more eyes (300) or the direction of the visual field of the one or more eyes (300).

6. The device according to any one of claims 1 to 5, wherein the controller (40) selects the temporal pattern, intensity, wavelength, spatial pattern, or duration of the emitted light.

7. The device according to any one of claims 1 to 6, further comprising one or more actuators for changing the position of the light source (34).

8. The device according to any one of claims 1 to 7, wherein the optical system is adapted to at least one of the position of the pupil of the one or more eyes (300) or the direction of the visual field of one of the one or more eyes (300).

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