Patent Application
20240108214
Amblyopia (commonly referred to as “lazy eye”) is a condition characterized by reduced vision in a structurally normal eye that results from maldevelopment of the visual system secondary to an abnormal binocular visual experience during infancy or early childhood.
Virtual reality headsets and 3D televisions create the percept of three dimensional space by presenting a slightly spatially different image to each eye. In general, the brain interprets the left-eye and right-eye views of the same scene as a single three-dimensional image (referred to as a stereoscopic image).
This specification describes technologies relating to the treatment of amblyopia.
In general, one innovative aspect of the subject matter described in this specification can be embodied in a system that includes a display system capable of delivering a second image to a second eye of a patient and a first image to a first eye of a patient. The system also includes a controller capable of delaying the delivery of the second image to the second eye of the patient. The controller is configured to receive the second image and the first image. The controller is also configured to identify a delay factor associated with the second image. The controller is also configured to provide the first image to the display system for viewing by the first eye of the patient. The controller is also configured such that after a delay determined by the delay factor, the controller provides the second image to the display system for viewing by the second eye of the patient.
The methods may include one or more of the following features, alone or in combination. The delay factor may be between 0 to 1000 milliseconds. The first image and the second image may be presented through a single display and selectively filtered to each eye. The display system may use polarization to selectively deliver the first image and the second image. The first image and the second image may be presented through separate displays or a single split display presented or projected to each eye. The first image and the second image may be part of a virtual reality experience. The first image and the second image may be part of an augmented reality experience. The delay factor may be determined at least in part by electrophysiologic measures including from VEPs and/or EEG recordings, by other visual measurements or tests, such as but not limited to eye tracking technologies, game-based tests of binocularity or inter-ocular suppression.
Other implementations of any of the above aspects include corresponding systems, apparatus, and computer programs that are configured to perform the actions of the methods, encoded on computer storage devices. The present disclosure also provides a computer-readable storage medium coupled to one or more processors and having instructions stored thereon which, when executed by the one or more processors, cause the one or more processors to perform operations in accordance with implementations of the methods provided herein. The present disclosure further provides a system for implementing the methods provided herein. The system includes one or more processors, and a computer-readable storage medium coupled to the one or more processors having instructions stored thereon which, when executed by the one or more processors, cause the one or more processors to perform operations in accordance with implementations of the methods provided herein.
Particular embodiments of the subject matter described in this specification can be implemented so as to realize one or more of the following advantages.
The details of one or more embodiments of the subject matter described in this specification are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages of the subject matter can become apparent from the description, the drawings, and the claims.
Like reference numbers and designations in the various drawings indicate like elements.
The mammalian visual cortex integrates signals from each eye and abides by basic principles of neural and synaptic plasticity. Plasticity, occurring at a single synapse, can in turn rewire neural circuits and change signal processing and integration within the nervous system; as such, synaptic plasticity is widely accepted as neurophysiologic model and mechanism for learning and memory. Decades of work in the mammalian brain has detailed the strong timing-dependence of integrated neural signals that influences the direction of synaptic plasticity as potentiation or depression. Amblyopia is a neurodevelopmental disease characterized by impairment in monocular vision that results from abnormal visual experience during visual development.
The capacity or tendency for plasticity, termed meta-plasticity, changes during neurodevelopment and in general reduces going from childhood into adulthood. This phenomenon is also demonstrated in amblyopia in the sense that treatment, aimed at strengthening the weaker eye through altering the subject's visual experience via methods discussed below, becomes ineffective if implemented after a certain age. Even within this “critical window” of cortical synaptic plasticity, occlusion (patching) therapy has limited efficacy with a high rate of failure. The efficacy of occlusion therapy may represent release of a suppressive role of the preferred eye that otherwise prevents recovery of vision in the amblyopic eye. Reduction of contrast in the fellow eye has also been employed to balance the visual utility of the eyes to minimize suppression, but this approach has shown similar efficacy to patching. Reducing contrast in the preferred eye of amblyopic patients has an immediate effect of reducing suppression to promote use of the affected eye.
The visually evoked potential (VEP) is a powerful physiologic measure of vision in non-communicative patients and animal models of amblyopia. Visual cortical responses, measured by VEP, are delayed (prolonged implicit time) with stimulation of the affected eye of patients with amblyopia ranging by 5-20 ms. There is also a direct relationship between the degree of visual deficit and the visual stimulus phase delay 106. Patch therapy (covering the preferred eye with a patch) improves the delay in VEP signals initiated in the affected eye of some 2-6 year old patients.
The delayed VEP implicit time is considered as a biomarker for amblyopia, but this delay may instead represent a mechanism by which the preferred eye acts to preclude recovery of the affected eye. As described herein, amblyopia may be treated by altering the timing of presentation of images to the preferred eye and the affected eye in order to facilitate synaptic plasticity in the visual cortex with the goal of increasing visual cortical responsiveness, and in turn visual function, of the affected eye. The present disclosure thus provides methods of treating subjects with amblyopia by altering the timing of presentation of images to the preferred eye and the affected eye in order to cause the brain to process images from the affected eye, e.g., using the devices described herein. Amblyopia can be diagnosed using methods known in the art, including by assessing fixation preference or by using forced preferential looking tests such as Teller cards, optical tracking, detecting lack of optokinetic nystagmus in one eye, neutral density filter testing, or visual evoked potentials (VEP) testing. See, e.g., Donaghy and Larson, “Vision screening for amblyopia.” EyeRounds.org. (Aug. 11, 2015; EyeRounds.org/tutorials/amblyopia/). The treatments can be provided daily, e.g., one, two, three, or more times daily, e.g., for at least 10, 20, 30, 40, 50, 60, or 90 minutes at a time, or less frequently, e.g., every other day, every third day, weekly, or monthly.
In some implementations, a subpart of an image is delayed to the eye. In some implementations, the delayed portion of the image may be related to the content of the image. For example, if an image included mountains in the background and a house in the foreground, only the portion of the image that includes the house may be delayed. In other implementations, a geometric portion of the image that is unrelated to the content of the image may be delayed (for example, a square portion, a circular portion, the left side, the right side, etc.)
In some implementations, the delay offset 206 may be determined, at least in part, by the refresh rate of the screen (or other presentation medium). For example, many screens and presentations devices have specific refresh rates. The refresh rate is the number of frames that can be presented in a second. A refresh rate of 60 Hz corresponds to the ability to present 60 frames per second (or 1 frame every 16.67 ms), 120 Hz corresponds to 120 frames per second (or 1 frames every 8.33 ms), 240 Hz corresponds to 240 frames per second (or 1 frame every 4.167 ms), etc.
In some implementations, the delay offset may be variable and adjusted based on testing of the user's visual system to determine the inherent lag between simultaneously originating singles from the deprived and fellow eyes as they travel from the retina to the primary visual cortex. The inherent lag may be ascertained by, for example, monitoring the P1, also known as P100, event related brain potential components by using, for example, electroencephalography (EEG). The inherent lag may also be determined using other methods. For example, in some implementations, the inherent lag may be determined by testing multiple delay times and then carrying out measurements at each level to determine when there is the desired response (improved binocularity).
In particular, EEG can be used to record the responses in the brain that arrived after a stimulus is presented to the user's eyes. The lag can be measured from the time the stimulus is delivered until the P100 response is detected. In some implementations, this lag corresponds to the lag applied to the frames in the video, or the degree of contrast applied to the video. The lag may be obtained by measuring the latencies from each eye stimulated separately, and then subtracting. In some implementations both eyes may be measured simultaneously while providing inputs to each.
In some implementations, the delay offset 206 may be described in terms of frames (1 frame on a 120 Hz presentation display corresponds to an 8.33 ms delay). In some implementations, a requested delay may be specified using a user interface 212 (for example, a user may request a 5 ms delay), the signal processor may translate the delay request to the closest delay amount supported by the presentations medium's refresh rate (for example, 8.33 ms). In other implementations, the user interface 212 may limit delay options based on the specifying refresh rates supported by the presentation medium.
The system can be adapted to use any presentation medium that enables the controlled delivery of images to the preferred eye and affected eye individually. Such presentation mediums include, but are not limited to, 3D televisions (using a single screen to project separate images to each eye through various methods), virtual reality systems (including but not limited to separate display systems projected to each eye that does not incorporate the subject's surrounding visual world), and augmented reality systems (including but not limited to separate display systems projected to each eye that does integrate the subject's surrounding visual world).
In some implementations, a single screen system can use chromatic filters to selectively display different images to each eye. Glasses may have colored lenses, e.g. one red and one cyan, also known as anaglyph glasses. The single screen would display signals comprising each of these colors with a predefined timing offset as described above. Another approach uses polarized filters in the glasses 304. The 3D television 302 displays two images projected from the screen using differentially polarized light. The reciprocally oriented polarizing filters, so the left lens selectively filters one set of images and the right lens selectively filters a separate set of images. The single screen projects selectively filterable images with a defined timing offset as described above.
Another form of a single screen system involves active-shutter glasses, and is commonly used in readily available 3D televisions. Battery powered glasses include a shuttering system that opens and closes the left and right lenses at very high speed. At a certain moment, the left lens is “open” and viewing the left-eye image on the TV screen while the right lens is occluded. A fraction of a second later, the glasses reverse: the right lens opens, the left lens is occluded. The images projected by the screen may change or alternate according to this shutter reversal. This enables the system to send different images to the left and right eye with control over timing of visual input.
In order to treat amblyopia, the system may interact with, for example, a device single or two-screen system to present two separate images or sets of images to a patient. Patients with ocular misalignment can have the necessary prismatic correction overlaid to achieve binocular viewing. Alternatively, separate images or sets of images can be presented via separate displays dedicated to each eye, such as in the form of glasses or goggles with separate displays within each ocular frame (such as a virtual reality headset). The images presented can be identical/superimposed, or can differ slightly with respect to perspective/spatial relationships between objects within the image to give the impression of depth (i.e. three dimensionality). Presentation of multiple shapes at a given flicker frequency with an interocular phase shift/delay can allow for visual acuity testing.
Visual stimuli/inputs can range from simple lines/shapes to complex videos such as movies or even immersive virtual environments. Phase delay technology can be combined with interactive modules to allow for feedback from the subject, a complex example of which is an interactive video game. Such an interface can be used to provide a readout for visual perception and monitor improvement and adherence to a given treatment regimen. Presentation of multiple shapes at a given flicker frequency and interocular phase shift can allow for testing of multiple forms of visual acuity, including but not limited to spatial acuity, temporal, spectral and stereoscopic acuities (which are differentially affected in amblyopia). Also, phase delay technology can also be combined with any form of digital media or arrangement of rendered pixels that is presentable using one of the herein described methods (e.g. virtual reality, 3D televisions, augmented reality, etc.), such as still images, TV/Movie content, computer operating systems, etc.
Concomitant VEP recordings can be used in conjunction with phase delay technology. The VEP recording, and interocular delay measured, can drive the Δτ offset in the visual input (feedback loop) to achieve a desired target for temporal integration. The present methods can also be used in conjunction with other treatment methods; for example, contrast can be altered in one or both eyes to balance the functional utility of one eye and/or to reduce suppression while phase delay is in place. Phase delay technology can be combined with virtual or augmented reality technologies as described above to immerse the patient in their visual experience. Phase delay can also be combined with other forms of virtual or augmented reality systems which use other sensory modalities, such as sound and tactile feedback. See, e.g., Hess and Thompson, 2015, for a description of other treatment methods that can be combined with the present methods.
The process 500 receives 502 an image. The image may be received from a data store, may be part of a movie, may be generated as part of a video game, or may be received from any other source. In some implementations, the process may receive an image for delivery to the preferred eye and a different image for delivery to the affected eye. In some implementations, the same image is delivered to the preferred eye and the affected eye.
The process 500 identifies a delay factor 502. The delay factor may indicate a number of frames, refreshes, or milliseconds to delay the presentation of the image to the preferred eye. The delay factor identified through visual acuity or electrophysiologic testing (VEP/EEG) will provide guidance in determining the Δτ offset, but the delay factor identified 504 may or may not equal the Δτ offset (508). Alternatively, in an interactive model, behavioral (i.e. psychophysical) responses of the subject may be used to determine the perception of an interocular timing delay. Those responses, in turn, could be used to influence the delay factor. The delay factor may or may not change over the course of treatment or implementation of this system as guided by measures obtained through methods including but not limited to electrophysiologic and psychophysical/behavioral means.
The process 500 provides 506 the image to the affected eye.
After a delay determined by the delay factor, the process 500 provides 508 the image to the preferred eye. In some implementations, this process may be reversed such that the first image is presented to the preferred eye and subsequently to the affected eye with a delay as determined by the delay factor.
A single screen was used to present exclusively polarized stimuli to the animal, and the stimuli were selectively filtered to each eye with a controlled offset in head-fixed mice. The stimulus consisted of a sinusoidal, 100% contrast grating at 0.05 cycles per degree in a fixed orientation. The tests included monocular and binocular testing at using stimuli of 4 different sinusoidal orientations: X+30 degrees, X+60 degrees, X+90 degrees, and X+120 degrees. Other ranges can also be used. Local field potentials (VEPs) were recorded through implanted electrodes in the striate cortex (V1 region). As in normal in prey animals, the VEP magnitude recorded in one primary visual cortical hemisphere is consistently smaller for the ipsilateral eye than that for the contralateral eye (relative to the cortical hemisphere being recorded) across all tests. The stimulus offset was such that the visual stimulus was presented to the eye contralateral to the recording electrode 16 ms before the same stimulus was presented to the ipsilateral eye. The visual stimulus was shown to the animal for 15 minutes at a rate of 0.5 Hz daily for 5 days. Two orthogonal orientations were run in parallel, one with an interocular stimulus offset (“Phase Delay”) and the other with no offset (No Delay). The final VEP magnitudes were compared to that produced by a third, novel stimulus orientation (“Novel Stimulus”). Graph 600 shows the VEP amplitude to time, in milliseconds. The bar graph 602 illustrates the VEP magnitude for the ipsilateral and contralateral visual stimuli, with respect to the side of visual cortex from which recordings were obtained. These conditions were compared to one another for the ipsilateral eye (A) as well as the contralateral eye (B). The magnitude of the ipsilateral VEP was significantly larger for the phase delay condition compared to the no delay and novel stimulus conditions, which were not different from one another. These results were consistently seen across a total of 3 adult animals and 3 juvenile animals tested in the same way. There were no differences seen across conditions for the contralateral eye. The bar graph 604 illustrates the ipsilateral/contralateral VEP signal ratio. Taking the ispilateral:contralateral VEP ratio, the same potentiating effect of phase delay was appreciated above the no delay and novel stimulus conditions (C). No SRP was appreciated in the no delay condition likely because monocular responses were tested in this condition. Similar results were seen across 2 animals in which the stimulus was presented to the ipsilateral eye and subsequently to the contralateral eye with the same 16 ms delay, that is, a potentiation was seen in the VEP signal corresponding to the ipsilateral eye (2 animals, data not shown). These data demonstrate that an interocular visual stimulus timing offset (i.e. phase delay) is sufficient to induce neural and/or synaptic plasticity in the mammalian visual cortex.
Embodiments of the subject matter and the operations described in this specification can be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Embodiments of the subject matter described in this specification can be implemented as one or more computer programs (i.e., one or more modules of computer program instructions, encoded on computer storage mediums for execution by, or to control the operation of, data processing apparatus). A computer storage medium can be, or be included in, a computer-readable storage device, a computer-readable storage substrate, a random or serial access memory array or device, or a combination of one or more of them. The computer storage medium can also be, or be included in, one or more separate physical components or media (e.g., multiple CDs, disks, or other storage devices). The computer storage medium can be non-transitory.
The operations described in this specification can be implemented as operations performed by a data processing apparatus on data stored on one or more computer-readable storage devices or received from other sources.
The term “data processing apparatus” encompasses all kinds of apparatus, devices, and machines for processing data, including by way of example, a programmable processor, a computer, a system on a chip, or multiple ones, or combinations, of the foregoing. The apparatus can include special purpose logic circuitry (e.g., an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit)). The apparatus can also include, in addition to hardware, code that creates an execution environment for the computer program in question (e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, a cross-platform runtime environment, a virtual machine, or a combination of one or more of them). The apparatus and execution environment can realize various different computing model infrastructures, such as web services, distributed computing and grid computing infrastructures.
A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural or object-oriented or functional languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, service, object, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub-programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.
The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform actions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry (e.g., an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit)).
Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital, analog or quantum computer. Generally, a processor can receive instructions and data from a read-only memory or a random access memory or both. The essential elements of a computer are a processor for performing actions in accordance with instructions and one or more memory devices for storing instructions and data. Generally, a computer can also include, or be operatively coupled to receive, data from or transfer data to, or both, one or more mass storage devices for storing data (e.g., electronic, magnetic, magneto-optical disks, or optical disks), however, a computer need not have such devices. Moreover, a computer can be embedded in another device (e.g., a mobile telephone, a personal digital assistant (PDA), a mobile audio or video player, a game console, a GPS receiver, or a portable storage device (e.g., a universal serial bus (USB) flash drive)), to name just a few. Devices suitable for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example semiconductor memory devices (e.g., EPROM, EEPROM, and flash memory devices), magnetic disks (e.g., internal hard disks or removable disks), magneto-optical disks, and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.
To provide for interaction with a user, embodiments of the subject matter described in this specification can be implemented on a computer having a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to the user and a keyboard and a pointing device (e.g., a mouse or a trackball) by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; for example, feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback) and input from the user can be received in any form, including acoustic, speech, or tactile input. In addition, a computer can interact with a user by sending documents to and receiving documents from a device that is used by the user (for example, by sending web pages to a web browser on a user's user device in response to requests received from the web browser).
Embodiments of the subject matter described in this specification can be implemented in a computing system that includes a back-end component (e.g., as a data server), a middleware component (e.g., an application server), or a front-end component (e.g., a user computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the subject matter described in this specification), or any combination of one or more such back-end, middleware, or front-end components. The components of the system can be interconnected by any form or medium of digital or optical data communication (e.g., a communication network). Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), an inter-network (e.g., the Internet), and peer-to-peer networks (e.g., ad hoc peer-to-peer networks).
The computing system can include users and servers. A user and server are generally remote from each other and typically interact through a communication network. The relationship of user and server arises by virtue of computer programs running on the respective computers and having a user-server relationship to each other. In some embodiments, a server transmits data (e.g., an HTML page) to a user device (e.g., for purposes of displaying data to and receiving user input from a user interacting with the user device). Data generated at the user device (e.g., a result of the user interaction) can be received from the user device at the server.
While this specification contains many specific implementation details, these should not be construed as limitations on the scope of any inventions or of what may be claimed, but rather as descriptions of features specific to particular embodiments of particular inventions. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can, in some cases, be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.
Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Moreover, the separation of various system components in the embodiments described above should not be understood as requiring such separation in all embodiments, and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products.
Thus, particular embodiments of the subject matter have been described. Other embodiments are within the scope of the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In certain implementations, multitasking and parallel processing may be advantageous.
This application is a divisional of U.S. patent application Ser. No. 16/345,632, filed Apr. 26, 2019, which is a 371 U.S. National Application of PCT/US2017/059775, filed on Nov. 2, 2017, which claims priority to U.S. Patent Application Ser. No. 62/448,479, filed on Jan. 20, 2017, and U.S. Patent Application Ser. No. 62/416,355, filed on Nov. 2, 2016. The entire contents of the foregoing are hereby incorporated by reference.
| Number | Date | Country | |
|---|---|---|---|
| 62448479 | Jan 2017 | US | |
| 62416355 | Nov 2016 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16345632 | Apr 2019 | US |
| Child | 18490502 | US |
