US20110218456A1 - Method and apparatus for objective electrophysiological assessment of visual function - Google Patents

Method and apparatus for objective electrophysiological assessment of visual function Download PDF

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US20110218456A1
US20110218456A1 US13/109,047 US201113109047A US2011218456A1 US 20110218456 A1 US20110218456 A1 US 20110218456A1 US 201113109047 A US201113109047 A US 201113109047A US 2011218456 A1 US2011218456 A1 US 2011218456A1
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eye
brain activity
visual
multifocal
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Stuart L. Graham
Iouri Malov
Alex Kozlovski
Alexander Klistorner
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University of Sydney
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University of Sydney
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Priority claimed from AUPQ6940A external-priority patent/AUPQ694000A0/en
Priority claimed from AUPR1982A external-priority patent/AUPR198200A0/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316Modalities, i.e. specific diagnostic methods
    • A61B5/369Electroencephalography [EEG]
    • A61B5/377Electroencephalography [EEG] using evoked responses
    • A61B5/378Visual stimuli
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316Modalities, i.e. specific diagnostic methods
    • A61B5/398Electrooculography [EOG], e.g. detecting nystagmus; Electroretinography [ERG]

Definitions

  • This invention relates to the electrophysiological assessment of visual function using a head mounted stereo display (eg virtual reality goggles) for displaying a stimulus which is used to generate a retinal or cortical response.
  • a head mounted stereo display eg virtual reality goggles
  • the integrity of the visual field can be assessed objectively by measuring retinal or cortical responses to a multifocal visual stimulus presented by a head mounted virtual reality display instead of a conventional monitor.
  • This provides advantages of space, patient acceptance, standardising distance to the display, and the possibility of monocular or binocular simultaneous recording.
  • the invention also describes scaling of the multifocal visual evoked potential (VEP) signals according to background electroencephalogram (EEG) levels, which reduces inter-individual variability.
  • VEP multifocal visual evoked potential
  • EEG background electroencephalogram
  • Multifocal ERG recording has been performed with various electrodes (gold foil, DTL, Burian-Allen, gold lens). Good correlation was reported between the multifocal VEP and visual field loss in glaucoma (refs 2, 5-7), and between the multifocal ERG and local retinal disease (ref 8), but not between the multifocal ERG and glaucoma (ref 9, 10).
  • the derivation of a functional map of the human visual field can be achieved from analysis of either multifocal VEP or ERG responses.
  • the VEP responses tend to reflect losses at all stages of the visual pathway, whereas the ERG responses tend to correlate with local retinal disease.
  • Malov International Patent Application No PCT/AU00/01483 that using a multifocal stimulus driven by a spread spectrum technique, (such that different parts of the visual field are stimulated by different random sequences), and by using appropriately placed recording electrodes on the scalp with multiple recording channels, that accurate maps of visual function can be recorded in the form of multifocal pattern VEPs.
  • glaucoma or optic nerve disorders that cause blind spots in the vision can be detected and mapped. Both amplitudes and latencies of the signals can be compared to normal reference values or compared between the two eyes of a subject.
  • a head mounted stereo display eg virtual reality goggles
  • a head mounted stereo display has good patient acceptance, and both monocular or binocular recording can be performed.
  • Simultaneous binocular recording can be achieved with the application of the spread spectrum technique (Malov, International Patent Application No PCT/AU00/01483) and a head mounted stereo display to provide different pseudorandom stimulus patterns to the two eyes at the same time.
  • the stimulus algorithm is divided into twice the number of segments and these can be distributed between the two eyes, still providing different stimulus sequences to each part of the field and with each subsequent run.
  • the cross-correlations can derive VEP results from each eye independently, with minimal auto-correlation of the signals within or between eyes. This has the advantage of shortening the test time significantly. It also standardises conditions of the recording such that the two eyes are recorded under the same conditions in terms of the subject's visual attention and extraneous noise levels. This aids in the reliability of direct comparisons between eyes of an individual.
  • the invention thus provides a method and apparatus for objectively assessing the visual field using virtual reality goggles to present a multifocal stimulus and then recording of either retinal (ERG) or cortical (VEP) responses to that stimulus. It includes simultaneous binocular recording of the VEP, using different stimuli for the two eyes. It also includes a new scaling method to reduce inter-subject variability in the recorded multifocal VEP amplitudes by scaling the VEP response according to overall electroencephalogram activity.
  • ERP retinal
  • VEP cortical
  • a suitable head mounted stereo display is what is commonly known as virtual reality goggles. Other head mounted displays which are able to present a suitable stimulus which can generate a retinal or cortical response would also be appropriate.
  • “Virtual reality” is a term applied to the experience of an individual when viewing through a head-mounted display an image presented immediately before the eyes which has the appearance of being viewed at a distance from the eye. Different images can be presented to the two eyes to give a three dimensional effect.
  • a method for objective electrophysiological assessment of visual function of at least one eye of a patient comprises presenting a visual stimulus to at least one eye of the patient, recording at least one resultant response, selected from the group consisting of a retinal response and a cortical response, generated as a result of the presenting; analysing said response; and as a result of said analysing, forming a map of the visual function of the at least one eye of the patient.
  • the presenting of the visual stimulus is achieved by a head mounted display, in particular a head mounted stereo display such as a head mounted virtual reality stereo display.
  • a method for objective electrophysiological assessment of visual function comprises placing a head-mounted stereo display for presenting a stimulus, on the head of a patient, placing electrodes on the scalp or in contact with the eye of said patient, connecting said head-mounted stereo display to a computer which generates an algorithm for driving said stimulus; generating said stimulus; recording the resultant retinal or cortical responses generated as a result of the stimulus; amplifying and analysing said responses; and as a result of said analysing, forming a map of the visual function.
  • a method of identifying alpha-rhythm spikes or electrocardiogram signals in raw data by application of Fourier spectrum analysis is important to identify these spikes prior to scaling since they may alert the operator to lack of visual attention of the patient.
  • a system for electrophysiological assessment of visual function of at least one eye of a patient comprising a head-mounted stereo display for presenting a stimulus to at least one eye of the patient; electrodes placed on the scalp or in contact with the eye; a computer which generates an algorithm for driving the stimulus; and a means for recording at least one resultant response, selected from the group consisting of a retinal response and a cortical response, generated as a result of presenting said stimulus; and means for recording the resultant retinal or cortical response; and software for analysing the retinal or cortical response to said stimulus.
  • a method for analysing at least one multifocal visual evoked potential recording from any mode of multifocal stimulation comprising scaling output from computer software according to overall spontaneous brain activity levels (ie. electroencephalogram levels) of a subject during the recording in order to minimise inter-subject variability.
  • the EEG scaling is more reliable if a method for removing high alpha-rhythm signals or electrocardiogram contamination is employed when calculating the background EEG levels.
  • the mode of multifocal stimulation includes conventional CRT or LCD monitors or plasma screens for example.
  • the head-mounted stereo display suitable comprises virtual reality goggles.
  • the head-mounted stereo display may be used to derive a signal from the cortical visual evoked potentials. It may also be used to derive an electroretinogram signal from the eye.
  • This display shows any type of multifocal stimulation directly to the eye.
  • the stimulus presented to the eye may be a flash stimulus or a pattern stimulus.
  • the stimulus may vary in luminance, colour or stimulus duration to elicit visual responses.
  • the head-mounted stereo display suitably uses a liquid crystal display or plasma screen, for example.
  • the stimulus may be presented monocularly or binocularly. The same stimulus may be presented binocularly for simultaneously recording of signals from both eyes.
  • the two eyes may be simultaneously presented binocularly for simultaneous recording to signals from the two eyes.
  • the results are scaled according to the overall spontaneous brain activity (i.e. electroencephalogram levels) of the subject during the recording to minimise variability.
  • the invention utilises multifocal stimulation techniques.
  • Any multifocal stimulator can be used to generate a stimulus which is then projected into virtual reality goggles using monocular or binocular displays.
  • the stimulus can be diffuse (flash) or structured (pattern) and can vary in intensity, colour, size or temporal characteristics.
  • Cross-correlation techniques allow for derivation of the signal from background noise.
  • a topographical map of the responses can then be derived corresponding to the field of view of the subject.
  • the output can displayed as a printout of results, and comparisons made with a normal data base of responses.
  • the inventors have applied a scaling factor based on background electroencephalogram (EEG) levels.
  • EEG background electroencephalogram
  • Scaling of the VEP amplitude based on amplitude of spontaneous brain activity eliminates part of the variability between individuals caused by differences in conductivity of underlying tissues (eg bone, muscle, skin and subcutaneous fat). This also reduces the differences seen between males and females, since it is known that women have generally higher amplitude VEP signals when compared to men, presumably due to sex differences in tissue thickness and conductivity. Scaling according to EEG signals removes this difference, rendering final signals equivalent between the sexes. By reducing the range of variability between subjects it improves the sensitivity of the test for detecting abnormality.
  • FIG. 1 is a schematic representation of the apparatus for VEP recording including virtual reality goggles
  • FIG. 2 is a schematic of the apparatus for ERG recording including virtual reality goggles
  • FIG. 3 is an example of a multifocal multichannel VEP recording from a normal subject using conventional screen ( FIG. 3A ) and goggles ( FIG. 3B );
  • FIG. 4A shows the printout from a subjective Humphrey visual field test with a scotoma demonstrated in the inferior visual field of the right eye of a glaucoma patient;
  • FIG. 4B shows a multifocal multichannel VEP recording using virtual reality goggles from the same eye as in FIG. 4A ;
  • FIG. 5 shows the correlation between multifocal VEP amplitude and electroencephalogram (EEG) levels during recording
  • FIG. 6A shows an example of normal Fourier spectrum of EEG used for scaling VEP results
  • FIG. 6B shows a trace with strong alpha-rhythm activity around 8 Hz which must be removed before scaling (for example by using a polynomial algorithm).
  • FIG. 6C shows rhythmic electrocardiogram spikes which also need to be excluded.
  • FIG. 1 shows a schematic of the apparatus for VEP recording using virtual reality goggles ( 1 ), which present the display to the subject.
  • the goggles are connected to a computer ( 2 ) with a linked video board that generates the multifocal stimulus.
  • the signals are conducted to an amplifier ( 3 ), before being processed by software for presentation on the operators display ( 4 ). Results can be compared for each eye, or between the two eyes of a subject, with respect to normal reference values.
  • FIG. 2 shows a schematic of the apparatus for multifocal ERG recording using virtual reality goggles ( 1 ).
  • the set up is the same as in FIG. 1 except that the recording electrode is placed in contact with the eye or eyelid.
  • a ground electrode is required (shown on the earlobe). Only one channel recording is required for the ERG.
  • FIG. 3 is an example of a multi focal multichannel VEP recording from the right and left eye of a normal subject.
  • FIG. 3A shows the responses achieved using a conventional screen (22 inch Hitachi monitor) to present the stimulus.
  • a cortically scaled dartboard stimulus was generated with 60 different areas of pattern stimulation using the ObjectiVision perimeter.
  • the trace array shown in the figure represents the responses generated from each part of the visual field tested out to 27 degrees of eccentricity temporally and 34 degrees nasally. For graphics purposes the central areas are relatively enlarged to show the raw VEP signal within that area.
  • FIG. 3B shows a multifocal multichannel VEP recordings from the same normal subject as in FIG. 3A , recorded using virtual reality goggles to present the same stimulus instead of the conventional monitor.
  • the same ObjectiVision system was used.
  • the responses are of similar order of magnitude in the two techniques, although there is some variation in amplitude across the field. Due to the specifications of the goggles used, the display was limited to 21 degrees temporally and 27
  • FIG. 4 provides a comparison between subjective perimetry findings and the objective VEP assessment of the visual field using virtual reality goggles.
  • FIG. 4A shows the grayscale and pattern deviation printout from a subjective Humphrey visual field test of the right eye of a glaucoma patient. An inferior arcuate scotoma (blind spot) is shown in the visual field.
  • FIG. 4B shows the multifocal multichannel VEP recording from the same eye as in FIG. 4A , recorded using virtual reality goggles. Analysis of the signals demonstrates loss of VEP responses corresponding to the inferior scotoma in FIG. 4A , with more extensive reductions in the superior field than seen on the Humphrey.
  • the amplitude deviation plot shades areas according to probability of abnormality when compared to a reference range of normal values extrapolated from the conventional screen ObjectiVision system. This suggests that the technique is capable of detecting visual field loss in glaucoma, just as it is with the use of the conventional large screen. It may also demonstrate more significant glaucomatous damage than suspected on conventional Humphrey field testing. Five glaucoma patients have been tested with the virtual reality goggles and the scotomas were detected in all five cases.
  • the level of spontaneous EEG activity is calculated during the recording, it provides an indirect measure of the overall registration of brain signals for that individual for the electrode positions used. Whilst it is recognised that EEG amplitude is determined by many additional factors other than conductivity, it is proposed that scaling of an individual's VEP responses according to their EEG levels, relative to normal population EEG values, helps to reduce inter-individual VEP variability.
  • the EEG amplitude is approximately 1000 ⁇ the amplitude of the VEP, so it is reasonable to assume that the VEP signals themselves will have little contribution to the raw EEG levels.
  • the EEG raw data is actually examined by cross-correlation techniques to extract the VEP signals.
  • the overall level of the raw EEG (99% confidence interval) as recorded during each run of the VEP recording can be used to provide an individual's scaling factor.
  • the VEP extracted is then scaled by the EEG scaling factor.
  • the value of the technique of the invention of VEP scaling was confirmed by examining the data from 50 normals.
  • the coefficient of variation for all 60 visual field test points had a mean value of 50.1%.
  • the coefficient of variation for all 60 visual field test points was reduced to 28.2%.
  • the EEG raw data can contain a large component of alpha rhythm signals and also spikes of electrocardiogram signals. If these are not excluded from the scaling factor applied, then some subjects will have their data inadvertently scaled down lower than is appropriate. This can introduce false positive results in the VEP.
  • One technique for rectifying this problem is to examine the raw signal by Fourier analysis and any alpha-rhythm spikes and electrocardiogram signals can be identified. These can then be excluded from the spectrum before calculating a scaling coefficient.
  • the method and system of this invention will find wide use in the medical field, specifically in the field of ophthalmology.

Abstract

For electrophysiological assessment of visual function using a head mounted stereo display (e.g. virtual reality goggles) for displaying a stimulus which is used to generate a retinal or cortical response. In particular, a method for objective electrophysiological assessment of visual function of at least one eye of a subject includes presenting a visual stimulus to at least one eye of the subject, recording at least one of a retinal response and, a cortical response generated as a result of the presenting; analyzing said response and, as a result of said analyzing, forming a map of the visual function of the at least one eye of the subject 6. The invention also relates to as system for such electrophysiological assessment.

Description

    TECHNICAL FIELD
  • This invention relates to the electrophysiological assessment of visual function using a head mounted stereo display (eg virtual reality goggles) for displaying a stimulus which is used to generate a retinal or cortical response. In particular, the integrity of the visual field can be assessed objectively by measuring retinal or cortical responses to a multifocal visual stimulus presented by a head mounted virtual reality display instead of a conventional monitor. This provides advantages of space, patient acceptance, standardising distance to the display, and the possibility of monocular or binocular simultaneous recording. The invention also describes scaling of the multifocal visual evoked potential (VEP) signals according to background electroencephalogram (EEG) levels, which reduces inter-individual variability.
  • BACKGROUND ART
  • The objective assessment of the visual field using multi-focal stimulation has been reported recently (refs 1-7). Using different types of multifocal stimulus presentation (Sutter U.S. Pat. No. 4,846,567; Malov, International Patent Application No PCT/AU00/01483; and refs 14-17, the disclosures of which are hereby being incorporated by reference), stimulation of a large number of locations of the visual field can be performed simultaneously. Visually evoked cortical potentials (VEP) and electroretinograms (ERG) can be recorded from all areas of the field. For the VEP various electrode placements have been used. The best representation of the visual field was reported by the inventors with multichannel bipolar recordings (Klistorner and Graham, International Patent Application No. PCT/AU99/00340). Multifocal ERG recording has been performed with various electrodes (gold foil, DTL, Burian-Allen, gold lens). Good correlation was reported between the multifocal VEP and visual field loss in glaucoma (refs 2, 5-7), and between the multifocal ERG and local retinal disease (ref 8), but not between the multifocal ERG and glaucoma (ref 9, 10).
  • However, these recordings require a high resolution, large screen display (22 inch or larger), and subjects are required to sit close to the screen. The distance of the subject from the screen changes the area of field stimulated, and also changes the focal length and thus the required spectacle correction, so must be closely controlled during the recording. The CRT monitor also produces a large electromagnetic field which may affect the recordings when the subject is in close proximity to the screen. Recording is limited to one eye at the time, whereas with goggles it is possible to present a different stimulus to the two eyes at the same time. Therefore the concept of using a head mounted display provides a solution to these problems, and saves significantly on space requirements. It also allows for portability of the system. Binocular simultaneous multifocal recording reduces the recording time up to 50% by allowing two eyes to be tested simultaneously using different stimulus sequences for the two eyes.
  • A significant problem with multifocal VEP recordings has been the large inter-individual variability seen among the normal population, which limits the sensitivity of applying values from a normal data base when looking for small changes early in the disease process. A scaling algorithm has previously been reported by us (Klistorner & Graham, International patent application No. PCT/AU99/00340) which helped to reduce this variability. However, the scaling of VEP amplitudes according to background electroencephalogram levels as described in this patent has been found to be a superior technique for reducing inter-individual variability and increasing the sensitivity of the test.
  • DISCLOSURE OF THE INVENTION
  • The derivation of a functional map of the human visual field can be achieved from analysis of either multifocal VEP or ERG responses. The VEP responses tend to reflect losses at all stages of the visual pathway, whereas the ERG responses tend to correlate with local retinal disease. It has been demonstrated by Malov, International Patent Application No PCT/AU00/01483 that using a multifocal stimulus driven by a spread spectrum technique, (such that different parts of the visual field are stimulated by different random sequences), and by using appropriately placed recording electrodes on the scalp with multiple recording channels, that accurate maps of visual function can be recorded in the form of multifocal pattern VEPs. Disease states such as glaucoma or optic nerve disorders that cause blind spots in the vision (eg optic neuritis in multiple sclerosis) can be detected and mapped. Both amplitudes and latencies of the signals can be compared to normal reference values or compared between the two eyes of a subject.
  • We have found that a head mounted stereo display (eg virtual reality goggles) can be applied to these recording techniques, providing significant advantages. It reduces the space required in the laboratory or test area by removing the need for a large monitor. It makes the test potentially portable, and it standardises the distance to the display reducing problems of refraction, variable head position and thus area of field tested. It removes the problem of electromagnetic noise emanating from the screen when the subject sits close to the monitor. A head mounted stereo display has good patient acceptance, and both monocular or binocular recording can be performed.
  • Simultaneous binocular recording can be achieved with the application of the spread spectrum technique (Malov, International Patent Application No PCT/AU00/01483) and a head mounted stereo display to provide different pseudorandom stimulus patterns to the two eyes at the same time. The stimulus algorithm is divided into twice the number of segments and these can be distributed between the two eyes, still providing different stimulus sequences to each part of the field and with each subsequent run. The cross-correlations can derive VEP results from each eye independently, with minimal auto-correlation of the signals within or between eyes. This has the advantage of shortening the test time significantly. It also standardises conditions of the recording such that the two eyes are recorded under the same conditions in terms of the subject's visual attention and extraneous noise levels. This aids in the reliability of direct comparisons between eyes of an individual.
  • The invention thus provides a method and apparatus for objectively assessing the visual field using virtual reality goggles to present a multifocal stimulus and then recording of either retinal (ERG) or cortical (VEP) responses to that stimulus. It includes simultaneous binocular recording of the VEP, using different stimuli for the two eyes. It also includes a new scaling method to reduce inter-subject variability in the recorded multifocal VEP amplitudes by scaling the VEP response according to overall electroencephalogram activity.
  • A suitable head mounted stereo display is what is commonly known as virtual reality goggles. Other head mounted displays which are able to present a suitable stimulus which can generate a retinal or cortical response would also be appropriate.
  • “Virtual reality” is a term applied to the experience of an individual when viewing through a head-mounted display an image presented immediately before the eyes which has the appearance of being viewed at a distance from the eye. Different images can be presented to the two eyes to give a three dimensional effect.
  • It is a purpose of this invention to provide a method and apparatus for recording of responses from multiple parts of the visual field using virtual reality goggles, and thus provide a compact, portable system that is acceptable for the patient and clinician, and removes the need for close monitoring of recording distances from the viewing screen.
  • According to one aspect of this invention there is provided a method for objective electrophysiological assessment of visual function of at least one eye of a patient, which method comprises presenting a visual stimulus to at least one eye of the patient, recording at least one resultant response, selected from the group consisting of a retinal response and a cortical response, generated as a result of the presenting; analysing said response; and as a result of said analysing, forming a map of the visual function of the at least one eye of the patient.
  • Usually, the presenting of the visual stimulus is achieved by a head mounted display, in particular a head mounted stereo display such as a head mounted virtual reality stereo display.
  • According to another aspect of this invention there is provided a method for objective electrophysiological assessment of visual function, which method comprises placing a head-mounted stereo display for presenting a stimulus, on the head of a patient, placing electrodes on the scalp or in contact with the eye of said patient, connecting said head-mounted stereo display to a computer which generates an algorithm for driving said stimulus; generating said stimulus; recording the resultant retinal or cortical responses generated as a result of the stimulus; amplifying and analysing said responses; and as a result of said analysing, forming a map of the visual function.
  • According to a further aspect of this invention there is provided a method of identifying alpha-rhythm spikes or electrocardiogram signals in raw data by application of Fourier spectrum analysis. (It is important to identify these spikes prior to scaling since they may alert the operator to lack of visual attention of the patient.)
  • According to a still further aspect of this invention there is provided a system for electrophysiological assessment of visual function of at least one eye of a patient, comprising a head-mounted stereo display for presenting a stimulus to at least one eye of the patient; electrodes placed on the scalp or in contact with the eye; a computer which generates an algorithm for driving the stimulus; and a means for recording at least one resultant response, selected from the group consisting of a retinal response and a cortical response, generated as a result of presenting said stimulus; and means for recording the resultant retinal or cortical response; and software for analysing the retinal or cortical response to said stimulus.
  • According to another aspect of this invention there is provided a method for analysing at least one multifocal visual evoked potential recording from any mode of multifocal stimulation comprising scaling output from computer software according to overall spontaneous brain activity levels (ie. electroencephalogram levels) of a subject during the recording in order to minimise inter-subject variability. The EEG scaling is more reliable if a method for removing high alpha-rhythm signals or electrocardiogram contamination is employed when calculating the background EEG levels. The mode of multifocal stimulation includes conventional CRT or LCD monitors or plasma screens for example.
  • As mentioned above, the head-mounted stereo display suitable comprises virtual reality goggles. The head-mounted stereo display may be used to derive a signal from the cortical visual evoked potentials. It may also be used to derive an electroretinogram signal from the eye. This display shows any type of multifocal stimulation directly to the eye. The stimulus presented to the eye may be a flash stimulus or a pattern stimulus. The stimulus may vary in luminance, colour or stimulus duration to elicit visual responses. The head-mounted stereo display suitably uses a liquid crystal display or plasma screen, for example. The stimulus may be presented monocularly or binocularly. The same stimulus may be presented binocularly for simultaneously recording of signals from both eyes. Where different stimuli are presented to the two eyes, they may be simultaneously presented binocularly for simultaneous recording to signals from the two eyes. For analysis of multifocal visual evoked potential recordings, the results are scaled according to the overall spontaneous brain activity (i.e. electroencephalogram levels) of the subject during the recording to minimise variability.
  • The invention utilises multifocal stimulation techniques. Any multifocal stimulator (either existing equipment such as ObjectiVision, VERIS, Retiscan, or future systems) can be used to generate a stimulus which is then projected into virtual reality goggles using monocular or binocular displays. We have established that both the ObjectiVision and VERIS systems can be used in recording with virtual reality goggles. The stimulus can be diffuse (flash) or structured (pattern) and can vary in intensity, colour, size or temporal characteristics. Appropriate electrodes placed on the scalp for the VEP, or in the eye for the ERG, allow for recording of the electrophysiological response, which is then amplified by a conventional amplifier. Cross-correlation techniques (eg, Malov, International Patent Application No PCT/AU00/01483) allow for derivation of the signal from background noise. A topographical map of the responses can then be derived corresponding to the field of view of the subject. The output can displayed as a printout of results, and comparisons made with a normal data base of responses.
  • To reduce the inter-individual variability of the multifocal VEP recordings the inventors have applied a scaling factor based on background electroencephalogram (EEG) levels. Scaling of the VEP amplitude based on amplitude of spontaneous brain activity eliminates part of the variability between individuals caused by differences in conductivity of underlying tissues (eg bone, muscle, skin and subcutaneous fat). This also reduces the differences seen between males and females, since it is known that women have generally higher amplitude VEP signals when compared to men, presumably due to sex differences in tissue thickness and conductivity. Scaling according to EEG signals removes this difference, rendering final signals equivalent between the sexes. By reducing the range of variability between subjects it improves the sensitivity of the test for detecting abnormality.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • A number of embodiments of the present invention will now be described with reference to the drawings in which:
  • FIG. 1 is a schematic representation of the apparatus for VEP recording including virtual reality goggles;
  • FIG. 2 is a schematic of the apparatus for ERG recording including virtual reality goggles;
  • FIG. 3 is an example of a multifocal multichannel VEP recording from a normal subject using conventional screen (FIG. 3A) and goggles (FIG. 3B);
  • FIG. 4A shows the printout from a subjective Humphrey visual field test with a scotoma demonstrated in the inferior visual field of the right eye of a glaucoma patient;
  • FIG. 4B shows a multifocal multichannel VEP recording using virtual reality goggles from the same eye as in FIG. 4A;
  • FIG. 5 shows the correlation between multifocal VEP amplitude and electroencephalogram (EEG) levels during recording;
  • FIG. 6A shows an example of normal Fourier spectrum of EEG used for scaling VEP results;
  • FIG. 6B shows a trace with strong alpha-rhythm activity around 8 Hz which must be removed before scaling (for example by using a polynomial algorithm); and
  • FIG. 6C shows rhythmic electrocardiogram spikes which also need to be excluded.
  • DESCRIPTION OF THE INVENTION
  • FIG. 1 shows a schematic of the apparatus for VEP recording using virtual reality goggles (1), which present the display to the subject. The goggles are connected to a computer (2) with a linked video board that generates the multifocal stimulus. Recording electrodes on the scalp (5) and a ground reference electrode (shown on the earlobe), detect the VEP signal from one or more recording channels (in this case four channels are shown). The signals are conducted to an amplifier (3), before being processed by software for presentation on the operators display (4). Results can be compared for each eye, or between the two eyes of a subject, with respect to normal reference values.
  • FIG. 2 shows a schematic of the apparatus for multifocal ERG recording using virtual reality goggles (1). The set up is the same as in FIG. 1 except that the recording electrode is placed in contact with the eye or eyelid. A ground electrode is required (shown on the earlobe). Only one channel recording is required for the ERG.
  • FIG. 3 is an example of a multi focal multichannel VEP recording from the right and left eye of a normal subject. FIG. 3A shows the responses achieved using a conventional screen (22 inch Hitachi monitor) to present the stimulus. A cortically scaled dartboard stimulus was generated with 60 different areas of pattern stimulation using the ObjectiVision perimeter. The trace array shown in the figure represents the responses generated from each part of the visual field tested out to 27 degrees of eccentricity temporally and 34 degrees nasally. For graphics purposes the central areas are relatively enlarged to show the raw VEP signal within that area. FIG. 3B shows a multifocal multichannel VEP recordings from the same normal subject as in FIG. 3A, recorded using virtual reality goggles to present the same stimulus instead of the conventional monitor. The same ObjectiVision system was used. The responses are of similar order of magnitude in the two techniques, although there is some variation in amplitude across the field. Due to the specifications of the goggles used, the display was limited to 21 degrees temporally and 27 degrees nasally.
  • FIG. 4 provides a comparison between subjective perimetry findings and the objective VEP assessment of the visual field using virtual reality goggles. FIG. 4A shows the grayscale and pattern deviation printout from a subjective Humphrey visual field test of the right eye of a glaucoma patient. An inferior arcuate scotoma (blind spot) is shown in the visual field. FIG. 4B shows the multifocal multichannel VEP recording from the same eye as in FIG. 4A, recorded using virtual reality goggles. Analysis of the signals demonstrates loss of VEP responses corresponding to the inferior scotoma in FIG. 4A, with more extensive reductions in the superior field than seen on the Humphrey. The amplitude deviation plot shades areas according to probability of abnormality when compared to a reference range of normal values extrapolated from the conventional screen ObjectiVision system. This suggests that the technique is capable of detecting visual field loss in glaucoma, just as it is with the use of the conventional large screen. It may also demonstrate more significant glaucomatous damage than suspected on conventional Humphrey field testing. Five glaucoma patients have been tested with the virtual reality goggles and the scotomas were detected in all five cases.
  • Examination of multifocal VEP data from normal subjects using conventional CRT monitors demonstrated that the amplitude of the multi-focal VEP is not age-dependant (contrary to most electrophysiology parameters, eg the pattern ERG). In fact, some elderly people produce VEP responses of higher amplitude. Individual variation in the thickness of the scalp or subcutaneous tissue may cause inter-individual differences in VEP amplitude due to variable impedance of bone and fat. Direct measurement of the thickness or impedance of these tissues is not currently practical. However, the impedance will also affect the amplitude of the spontaneous brain activity (EEG) in a similar fashion to the VEP. To confirm this we conducted a study using the ObjectiVision VEP perimeter of the correspondence between spontaneous EEG amplitude (99% confidence interval) and multifocal VEP amplitude (largest amplitude of a trace). The study included 34 normal subjects. The results demonstrated a strong correlation between the EEG amplitude and VEP (correlation coefficient r=0.81). The scatterplot for the correlation is shown in FIG. 5. An alternative method to measure background EEG activity is to calculate a Fourier power spectrum of the EEG.
  • Therefore, if the level of spontaneous EEG activity is calculated during the recording, it provides an indirect measure of the overall registration of brain signals for that individual for the electrode positions used. Whilst it is recognised that EEG amplitude is determined by many additional factors other than conductivity, it is proposed that scaling of an individual's VEP responses according to their EEG levels, relative to normal population EEG values, helps to reduce inter-individual VEP variability.
  • The EEG amplitude is approximately 1000× the amplitude of the VEP, so it is reasonable to assume that the VEP signals themselves will have little contribution to the raw EEG levels. In analysis of multifocal VEP recordings the EEG raw data is actually examined by cross-correlation techniques to extract the VEP signals. When recording from an individual, the overall level of the raw EEG (99% confidence interval) as recorded during each run of the VEP recording, can be used to provide an individual's scaling factor. The VEP extracted is then scaled by the EEG scaling factor.
  • The value of the technique of the invention of VEP scaling was confirmed by examining the data from 50 normals. The coefficient of variation for all 60 visual field test points had a mean value of 50.1%. When the results were scaled according to background EEG values the coefficient of variation for all 60 visual field test points was reduced to 28.2%.
  • By using EEG scaling, the sensitivity of the test was also improved. In a study of 60 glaucoma cases using the ObjectiVision system for multifocal VEP perimetry, several glaucoma cases were not flagged as abnormal using the unsealed data since the subjects had overall large signals compared with normal, even though focal relative reductions could be seen when examining the trace arrays. With the data scaled according to EEG levels however, these subjects were identified as having localised reductions in their VEP amplitudes and the scotomas were flagged appropriately.
  • The EEG raw data can contain a large component of alpha rhythm signals and also spikes of electrocardiogram signals. If these are not excluded from the scaling factor applied, then some subjects will have their data inadvertently scaled down lower than is appropriate. This can introduce false positive results in the VEP. One technique for rectifying this problem is to examine the raw signal by Fourier analysis and any alpha-rhythm spikes and electrocardiogram signals can be identified. These can then be excluded from the spectrum before calculating a scaling coefficient.
  • Therefore scaling of the VEP amplitude based on amplitude of spontaneous brain activity eliminates part of the variability between individuals caused by differences in conductivity of tissues. This technique has application in analysing multifocal VEP signals recorded with conventional CRT monitors, plasma screens, LCD screens, or with virtual reality goggles.
  • INDUSTRIAL APPLICABILITY
  • The method and system of this invention will find wide use in the medical field, specifically in the field of ophthalmology.
  • The foregoing describes only some embodiments of the invention and modifications can be made thereto without departing from the scope of the invention.
  • REFERENCES
    • 1. Baseler H A & Sutter E E. Vis Research 1997; 37(6):675-790
    • 2. Klistorner A I, et al Invest Ophthalmol Vis Sci 1998; 39(6):937-950
    • 3. Klistorner A I, et al Aust N Z J Ophthalmol 1998; 26:91-94.
    • 4. Graham S L, & Klistorner A. Aust N Z J Ophthalmol 1998; 26:71-85
    • 5. Graham S L, et al Surv Ophthalmol 1999; 43 (Suppl1):s199-209
    • 6. Graham S L & Klistorner A. Curr Opin Ophthalmol 1999; 10:140-146.
    • 7. Graham S L, et al J Glaucoma 2000; 9, 10-19
    • 8. Kondo, M, et al Invest Ophthalmol Vis Sci, 1995; 36:2146-2150
    • 9. Vaegan & Buckland L. ANZ J Ophthalmol 1996; 24(2):28-31
    • 10. Johnson C A, et al J Glaucoma 2000; 9(AGS abstract):110
    • 11. U.S. Pat. No. 4,846,567 (Sutter)
    • 12. Graham S et al Vol 40 Invest Ophthalmol Vis Sci, 1999, 40 (4) ARVO Abstract #318
    • 13. U.S. Pat. No. 5,539,482 (James & Maddess)
    • 14. GoldR IEEE Trans, 1967, V.IT-13 (4) 619-621
    • 15. Sarwate & Pursley. Proc IEEE, 1980, Vol 68 (5) 593-619
    • 16. Olsen et al IEEE Trans, 1982, V.IT-28(6) 858-864
    • 17. Kamaletdinov B. Problems of Information Transmission, 1988, Vol 23 (2) 104-107
    • 18. Klistorner PCT/AU99/00340

Claims (8)

1. An apparatusus for analysing at least one multifocal visual evoked potential response of at least two subjects, the at least one visual evoked potential response being induced by any mode of multifocal stimulation, wherein the stimulation mode is adapted to simultaneously stimulate different parts of the visual field of an eye of the subject such that different parts of the visual field are stimulated with random sequences of different timing or character, the apparatus comprising:
(a) electrodes placed on the scalp or in contact with the eye of each subject configured to simultaneously record (A) the at least one visual evoked potential responses from each of the different parts of the visual field of the eye and (B) the subject's overall spontaneous brain activity levels; and
(b) a computer configured to:
(bi) identify, for each subject, the alpha rhythm component in the subject's overall spontaneous brain activity levels,
(bii) remove, for each subject, the alpha rhythm component from the subject's overall spontaneous brain activity levels;
(biii) calculate, for each subject, a corresponding scaling factor, the scaling factor being derived from the subject's overall spontaneous brain activity levels from which the component of alpha rhythm is identified and removed; and
(biv) scale, for each subject, each subject's visual evoked potential response using said each subject's scaling factor such that the variability of the visual evoked potential responses induced by the multifocal stimulation between the at least two subjects is minimised.
2. The apparatus of claim 1, wherein the alpha rhythm component in the subject's overall spontaneous brain activity levels is identified by wave component analysis.
3. The apparatus of claim 2, wherein the alpha rhythm component in the subject's overall spontaneous brain activity levels is identified by Fourier analysis.
4. The apparatus of claim 1, wherein step (bi) comprises:
for each subject, using Fourier power spectrum analysis to determine the subject's overall spontaneous brain activity levels, thereby to calculate a scaling factor.
5. The apparatus of claim 1, wherein the multifocal stimulation stimulates responses from different parts of the visual field of both eyes of the subject and the responses from each of the different parts of the visual field for each eye are recorded simultaneously.
6. The apparatus of claim 1, wherein the computer is further configured to:
(bv) identify and remove the effect of electrocardiogram spikes.
7. The apparatus of claim 3, wherein the electrocardiogram spikes are identified by Fourier analysis of the subject's recorded overall spontaneous brain activity levels.
8. The apparatus of claim 1, further comprising at least one of storing and displaying said evoked potential response.
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WO2016182974A1 (en) * 2015-05-08 2016-11-17 Ngoggle Head-mounted display eeg device
US20170000342A1 (en) 2015-03-16 2017-01-05 Magic Leap, Inc. Methods and systems for detecting health conditions by imaging portions of the eye, including the fundus
US20180110409A1 (en) * 2016-10-20 2018-04-26 Stylianos Georgios Tsapakis Visual field test method/perimeter using virtual reality glasses/headset and a smartphone or tablet or other portable device
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US10459231B2 (en) 2016-04-08 2019-10-29 Magic Leap, Inc. Augmented reality systems and methods with variable focus lens elements
US10667683B2 (en) 2018-09-21 2020-06-02 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0113533D0 (en) 2001-06-05 2001-07-25 Brigantia Software Ltd Apparatus and method for testing visual response
GB2382252A (en) * 2001-10-13 2003-05-21 Alki Liasis Portable visual stimulators
US7549749B2 (en) 2002-05-06 2009-06-23 Antti Valjakka Visual stimulator
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US7922670B2 (en) * 2005-02-24 2011-04-12 Warren Jones System and method for quantifying and mapping visual salience
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AU2008215181A1 (en) 2007-02-16 2008-08-21 Objectivision Limited Stimulus method for multifocal visual evoked potential
US20090040296A1 (en) * 2007-08-06 2009-02-12 Moscato Jonathan D Head mounted display assembly
US8083354B2 (en) * 2007-10-03 2011-12-27 Diopsys, Inc. Simultaneously multi-temporal visual test and method and apparatus therefor
WO2009059380A1 (en) * 2007-11-09 2009-05-14 The Australian National University Method and apparatus for sensory field assessment
JP5076065B2 (en) * 2008-06-13 2012-11-21 国立大学法人福井大学 Optic nerve activity measurement support device
WO2010006180A1 (en) 2008-07-09 2010-01-14 Mckinley Laurence M Optic function monitoring process and apparatus
DE102008056976B4 (en) * 2008-11-07 2010-09-02 Technische Universität Ilmenau Method and device for multifocal, color channel-selective stimulation of the visual system
AU2010225433B2 (en) * 2009-03-20 2015-12-24 Cognisens Inc. Device and method for measuring mild perceptual impairment
US20120172419A1 (en) * 2009-09-15 2012-07-05 Medical College Of Wisconsin Research Foundation Inc. Reagents and methods for modulating cone photoreceptor activity
US20110066082A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of visual motor response
US20110066069A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of visual form discrimination
US20110065070A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of letter identification latency
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US20110065073A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of word detection latency
US8777630B2 (en) 2009-09-16 2014-07-15 Cerebral Assessment Systems, Inc. Method and system for quantitative assessment of facial emotion sensitivity
US20110065071A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of word identification latency
US20110065069A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of verbal recognition memory
US20110065072A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of word recognition sensitivity
US20110066068A1 (en) * 2009-09-16 2011-03-17 Duffy Charles J Method and system for quantitative assessment of functional impairment
US8475391B2 (en) * 2009-09-16 2013-07-02 Cerebral Assessment Systems Method and system for quantitative assessment of spatial distractor tasks
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AU2014334870B2 (en) 2013-10-17 2019-06-13 Children's Healthcare Of Atlanta, Inc. Methods for assessing infant and child development via eye tracking
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US10413172B2 (en) 2017-12-11 2019-09-17 1-800 Contacts, Inc. Digital visual acuity eye examination for remote physician assessment
CN109222970A (en) * 2018-07-09 2019-01-18 司法鉴定科学研究院 The equipment of eyesight objective evaluation and the detection system of visual evoked potential and method
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US20210315508A1 (en) * 2020-04-14 2021-10-14 Neurotype Inc. Assessing Motivated Attention with Cue Reactivity

Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4255023A (en) * 1979-02-12 1981-03-10 House Harold D Objective retinal response recorder
US4320768A (en) * 1979-07-17 1982-03-23 Georgetown University Medical Center Computerized electro-oculographic (CEOG) system
US4493539A (en) * 1982-06-30 1985-01-15 The United States Of America As Represented By The Secretary Of The Air Force Method and apparatus for objective determination of visual contrast sensitivity functions
US4697598A (en) * 1985-04-25 1987-10-06 Westinghouse Electric Corp. Evoked potential autorefractometry system
US4736751A (en) * 1986-12-16 1988-04-12 Eeg Systems Laboratory Brain wave source network location scanning method and system
US4832480A (en) * 1986-06-24 1989-05-23 Quintron, Inc. Differential diagnosis of sensory abnormalities using a normalized, ratiometric analysis of steady state evoked potentials
US4846567A (en) * 1986-08-06 1989-07-11 Sutter Erich E Retinal area response mapping using simultaneous multi-area stimulation with binary sequences and objective response analysis
US4861154A (en) * 1986-08-06 1989-08-29 Westinghouse Electric Corp. Automated visual assessment system with steady state visual evoked potential stimulator and product detector
US4955389A (en) * 1987-07-27 1990-09-11 Siemens Aktiengesellschaft Apparatus for stimulation with optical stimuli
US5458117A (en) * 1991-10-25 1995-10-17 Aspect Medical Systems, Inc. Cerebral biopotential analysis system and method
US5609158A (en) * 1995-05-01 1997-03-11 Arrhythmia Research Technology, Inc. Apparatus and method for predicting cardiac arrhythmia by detection of micropotentials and analysis of all ECG segments and intervals
US5844824A (en) * 1995-10-02 1998-12-01 Xybernaut Corporation Hands-free, portable computer and system
US6044292A (en) * 1998-09-21 2000-03-28 Heyrend; F. Lamarr Apparatus and method for predicting probability of explosive behavior in people
US6260970B1 (en) * 1996-05-21 2001-07-17 Health Performance, Inc. Vision screening system
US6315414B1 (en) * 1998-03-30 2001-11-13 Australian National University Simultaneous binocular assessment of multiple optic nerve and cortical regions in diseases affecting nerve condition
US6364845B1 (en) * 1998-09-17 2002-04-02 University Of Rochester Methods for diagnosing visuospatial disorientation or assessing visuospatial orientation capacity
US6966650B2 (en) * 2003-06-27 2005-11-22 Zongqi Hu Method and apparatus for an automated procedure to detect and monitor early-stage glaucoma
US7220000B2 (en) * 2002-02-19 2007-05-22 Notal Vision Inc. Methods, devices and systems for assessing eye disease
US7275830B2 (en) * 2000-10-06 2007-10-02 Notal Vision Inc. Methods devices and systems for detecting eye disease
US7384145B2 (en) * 2006-02-16 2008-06-10 The Board Of Trustees Of The University Of Illinois Mapping retinal function using corneal electrode array
US7645140B2 (en) * 2002-11-05 2010-01-12 University Of Rochester Medical Center Method for assessing navigational capacity
US7665847B2 (en) * 2003-05-05 2010-02-23 Reichert, Inc. Eye mapping
US7682021B2 (en) * 2002-02-08 2010-03-23 Novavision, Inc. System and methods for the treatment of retinal diseases

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4474186A (en) * 1979-07-17 1984-10-02 Georgetown University Computerized electro-oculographic (CEOG) system with feedback control of stimuli
US5539482A (en) 1992-02-28 1996-07-23 The Australian National University Glaucoma testing using non-linear systems identification techniques
DE4301483A1 (en) * 1993-01-21 1994-08-11 Otto Sembritzki Device for generating photostimuli and for measuring the electroretinogram and the visual evoked cortical potential
JP2819401B2 (en) * 1994-08-23 1998-10-30 里子 佐藤 EEG and ECG recording device
KR100349709B1 (en) 1997-12-23 2002-11-23 삼성전자 주식회사 Stator of linear compressor
US6086206A (en) * 1998-01-05 2000-07-11 Sutter; Erich E. Analysis method for enhancing and extracting second order nonlinear response components of the multi-area electroretinogram
DE69937234T2 (en) * 1998-05-08 2008-07-03 The University Of Sydney, Sydney ELECTROPHYSIOLOGICAL MEASUREMENT OF THE FACE
WO2001039659A1 (en) 1999-12-03 2001-06-07 Iouri Malov Field testing using spread spectrum technique

Patent Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4255023A (en) * 1979-02-12 1981-03-10 House Harold D Objective retinal response recorder
US4320768A (en) * 1979-07-17 1982-03-23 Georgetown University Medical Center Computerized electro-oculographic (CEOG) system
US4493539A (en) * 1982-06-30 1985-01-15 The United States Of America As Represented By The Secretary Of The Air Force Method and apparatus for objective determination of visual contrast sensitivity functions
US4697598A (en) * 1985-04-25 1987-10-06 Westinghouse Electric Corp. Evoked potential autorefractometry system
US4832480A (en) * 1986-06-24 1989-05-23 Quintron, Inc. Differential diagnosis of sensory abnormalities using a normalized, ratiometric analysis of steady state evoked potentials
US4846567A (en) * 1986-08-06 1989-07-11 Sutter Erich E Retinal area response mapping using simultaneous multi-area stimulation with binary sequences and objective response analysis
US4861154A (en) * 1986-08-06 1989-08-29 Westinghouse Electric Corp. Automated visual assessment system with steady state visual evoked potential stimulator and product detector
US4736751A (en) * 1986-12-16 1988-04-12 Eeg Systems Laboratory Brain wave source network location scanning method and system
US4955389A (en) * 1987-07-27 1990-09-11 Siemens Aktiengesellschaft Apparatus for stimulation with optical stimuli
US5458117A (en) * 1991-10-25 1995-10-17 Aspect Medical Systems, Inc. Cerebral biopotential analysis system and method
US5609158A (en) * 1995-05-01 1997-03-11 Arrhythmia Research Technology, Inc. Apparatus and method for predicting cardiac arrhythmia by detection of micropotentials and analysis of all ECG segments and intervals
US5844824A (en) * 1995-10-02 1998-12-01 Xybernaut Corporation Hands-free, portable computer and system
US6260970B1 (en) * 1996-05-21 2001-07-17 Health Performance, Inc. Vision screening system
US6315414B1 (en) * 1998-03-30 2001-11-13 Australian National University Simultaneous binocular assessment of multiple optic nerve and cortical regions in diseases affecting nerve condition
US6364845B1 (en) * 1998-09-17 2002-04-02 University Of Rochester Methods for diagnosing visuospatial disorientation or assessing visuospatial orientation capacity
US6044292A (en) * 1998-09-21 2000-03-28 Heyrend; F. Lamarr Apparatus and method for predicting probability of explosive behavior in people
US7275830B2 (en) * 2000-10-06 2007-10-02 Notal Vision Inc. Methods devices and systems for detecting eye disease
US7682021B2 (en) * 2002-02-08 2010-03-23 Novavision, Inc. System and methods for the treatment of retinal diseases
US7220000B2 (en) * 2002-02-19 2007-05-22 Notal Vision Inc. Methods, devices and systems for assessing eye disease
US7645140B2 (en) * 2002-11-05 2010-01-12 University Of Rochester Medical Center Method for assessing navigational capacity
US7665847B2 (en) * 2003-05-05 2010-02-23 Reichert, Inc. Eye mapping
US6966650B2 (en) * 2003-06-27 2005-11-22 Zongqi Hu Method and apparatus for an automated procedure to detect and monitor early-stage glaucoma
US7384145B2 (en) * 2006-02-16 2008-06-10 The Board Of Trustees Of The University Of Illinois Mapping retinal function using corneal electrode array

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10073280B2 (en) * 2012-05-30 2018-09-11 Tokai Optical Co., Ltd. Method for assessing spectacle lens by evoked activity in visual cortex of brain or the like, and method for designing spectacle lens using said method for assessment
US20150133811A1 (en) * 2012-05-30 2015-05-14 Masaya Suzuki Method for assessing spectacle lens by evoked activity in visual cortex of brain or the like, and method for designing spectacle lens using said method for assessment
US10473934B2 (en) 2015-03-16 2019-11-12 Magic Leap, Inc. Methods and systems for performing slit lamp examination
US10371947B2 (en) 2015-03-16 2019-08-06 Magic Leap, Inc. Methods and systems for modifying eye convergence for diagnosing and treating conditions including strabismus and/or amblyopia
US20170007450A1 (en) 2015-03-16 2017-01-12 Magic Leap, Inc. Augmented and virtual reality display systems and methods for delivery of medication to eyes
US11747627B2 (en) 2015-03-16 2023-09-05 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing health conditions based on visual fields
US11474359B2 (en) 2015-03-16 2022-10-18 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing health conditions based on visual fields
US11256096B2 (en) 2015-03-16 2022-02-22 Magic Leap, Inc. Methods and systems for diagnosing and treating presbyopia
US20170000342A1 (en) 2015-03-16 2017-01-05 Magic Leap, Inc. Methods and systems for detecting health conditions by imaging portions of the eye, including the fundus
US10345592B2 (en) 2015-03-16 2019-07-09 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing a user using electrical potentials
US10345590B2 (en) 2015-03-16 2019-07-09 Magic Leap, Inc. Augmented and virtual reality display systems and methods for determining optical prescriptions
US10345591B2 (en) 2015-03-16 2019-07-09 Magic Leap, Inc. Methods and systems for performing retinoscopy
US10345593B2 (en) 2015-03-16 2019-07-09 Magic Leap, Inc. Methods and systems for providing augmented reality content for treating color blindness
US10359631B2 (en) 2015-03-16 2019-07-23 Magic Leap, Inc. Augmented reality display systems and methods for re-rendering the world
US10365488B2 (en) 2015-03-16 2019-07-30 Magic Leap, Inc. Methods and systems for diagnosing eyes using aberrometer
US10527850B2 (en) 2015-03-16 2020-01-07 Magic Leap, Inc. Augmented and virtual reality display systems and methods for determining optical prescriptions by imaging retina
US10371949B2 (en) 2015-03-16 2019-08-06 Magic Leap, Inc. Methods and systems for performing confocal microscopy
US10371945B2 (en) 2015-03-16 2019-08-06 Magic Leap, Inc. Methods and systems for diagnosing and treating higher order refractive aberrations of an eye
US10371948B2 (en) 2015-03-16 2019-08-06 Magic Leap, Inc. Methods and systems for diagnosing color blindness
US10371946B2 (en) 2015-03-16 2019-08-06 Magic Leap, Inc. Methods and systems for diagnosing binocular vision conditions
US10379354B2 (en) 2015-03-16 2019-08-13 Magic Leap, Inc. Methods and systems for diagnosing contrast sensitivity
US10379351B2 (en) 2015-03-16 2019-08-13 Magic Leap, Inc. Methods and systems for diagnosing and treating eyes using light therapy
US10379350B2 (en) 2015-03-16 2019-08-13 Magic Leap, Inc. Methods and systems for diagnosing eyes using ultrasound
US10379353B2 (en) 2015-03-16 2019-08-13 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing health conditions based on visual fields
US10386640B2 (en) 2015-03-16 2019-08-20 Magic Leap, Inc. Methods and systems for determining intraocular pressure
US10386639B2 (en) 2015-03-16 2019-08-20 Magic Leap, Inc. Methods and systems for diagnosing eye conditions such as red reflex using light reflected from the eyes
US10539794B2 (en) 2015-03-16 2020-01-21 Magic Leap, Inc. Methods and systems for detecting health conditions by imaging portions of the eye, including the fundus
US10429649B2 (en) 2015-03-16 2019-10-01 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing using occluder
US10437062B2 (en) 2015-03-16 2019-10-08 Magic Leap, Inc. Augmented and virtual reality display platforms and methods for delivering health treatments to a user
US10444504B2 (en) 2015-03-16 2019-10-15 Magic Leap, Inc. Methods and systems for performing optical coherence tomography
US10451877B2 (en) 2015-03-16 2019-10-22 Magic Leap, Inc. Methods and systems for diagnosing and treating presbyopia
US10459229B2 (en) 2015-03-16 2019-10-29 Magic Leap, Inc. Methods and systems for performing two-photon microscopy
US11156835B2 (en) 2015-03-16 2021-10-26 Magic Leap, Inc. Methods and systems for diagnosing and treating health ailments
US10466477B2 (en) 2015-03-16 2019-11-05 Magic Leap, Inc. Methods and systems for providing wavefront corrections for treating conditions including myopia, hyperopia, and/or astigmatism
US10788675B2 (en) 2015-03-16 2020-09-29 Magic Leap, Inc. Methods and systems for diagnosing and treating eyes using light therapy
US20170007843A1 (en) 2015-03-16 2017-01-12 Magic Leap, Inc. Methods and systems for diagnosing and treating eyes using laser therapy
US10386641B2 (en) 2015-03-16 2019-08-20 Magic Leap, Inc. Methods and systems for providing augmented reality content for treatment of macular degeneration
US10539795B2 (en) 2015-03-16 2020-01-21 Magic Leap, Inc. Methods and systems for diagnosing and treating eyes using laser therapy
US10545341B2 (en) 2015-03-16 2020-01-28 Magic Leap, Inc. Methods and systems for diagnosing eye conditions, including macular degeneration
US10564423B2 (en) 2015-03-16 2020-02-18 Magic Leap, Inc. Augmented and virtual reality display systems and methods for delivery of medication to eyes
US10983351B2 (en) 2015-03-16 2021-04-20 Magic Leap, Inc. Augmented and virtual reality display systems and methods for diagnosing health conditions based on visual fields
US10775628B2 (en) 2015-03-16 2020-09-15 Magic Leap, Inc. Methods and systems for diagnosing and treating presbyopia
US10969588B2 (en) 2015-03-16 2021-04-06 Magic Leap, Inc. Methods and systems for diagnosing contrast sensitivity
WO2016182974A1 (en) * 2015-05-08 2016-11-17 Ngoggle Head-mounted display eeg device
US20180103917A1 (en) * 2015-05-08 2018-04-19 Ngoggle Head-mounted display eeg device
EP3305206A4 (en) * 2015-06-05 2018-06-20 Shikuukankoubou Co., Ltd. Program and system for early detection and prevention of mild dementia
US11000221B2 (en) 2015-06-05 2021-05-11 Shikuukankoubou Co., Ltd. Program and system for early detection and prevention of mild dementia
US10459231B2 (en) 2016-04-08 2019-10-29 Magic Leap, Inc. Augmented reality systems and methods with variable focus lens elements
US11614626B2 (en) 2016-04-08 2023-03-28 Magic Leap, Inc. Augmented reality systems and methods with variable focus lens elements
US11106041B2 (en) 2016-04-08 2021-08-31 Magic Leap, Inc. Augmented reality systems and methods with variable focus lens elements
US20180110409A1 (en) * 2016-10-20 2018-04-26 Stylianos Georgios Tsapakis Visual field test method/perimeter using virtual reality glasses/headset and a smartphone or tablet or other portable device
US10962855B2 (en) 2017-02-23 2021-03-30 Magic Leap, Inc. Display system with variable power reflector
US11774823B2 (en) 2017-02-23 2023-10-03 Magic Leap, Inc. Display system with variable power reflector
US11300844B2 (en) 2017-02-23 2022-04-12 Magic Leap, Inc. Display system with variable power reflector
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US11273283B2 (en) 2017-12-31 2022-03-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11318277B2 (en) 2017-12-31 2022-05-03 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11478603B2 (en) 2017-12-31 2022-10-25 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
US11452839B2 (en) 2018-09-14 2022-09-27 Neuroenhancement Lab, LLC System and method of improving sleep
US11457805B2 (en) 2018-09-21 2022-10-04 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US11478143B2 (en) 2018-09-21 2022-10-25 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US11478142B2 (en) 2018-09-21 2022-10-25 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US11471044B2 (en) 2018-09-21 2022-10-18 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US10667683B2 (en) 2018-09-21 2020-06-02 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US11344194B2 (en) 2018-09-21 2022-05-31 MacuLogix, Inc. Methods, apparatus, and systems for ophthalmic testing and measurement
US11089954B2 (en) 2018-09-21 2021-08-17 MacuLogix, Inc. Method and apparatus for guiding a test subject through an ophthalmic test
US11786694B2 (en) 2019-05-24 2023-10-17 NeuroLight, Inc. Device, method, and app for facilitating sleep
WO2022109409A1 (en) * 2020-11-20 2022-05-27 Diagnosys LLC Methods and apparatus for performing enhanced full-field stimulus threshold (fst) tests

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US7740592B2 (en) 2010-06-22
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US20090076406A1 (en) 2009-03-19
US7972278B2 (en) 2011-07-05
JP4817582B2 (en) 2011-11-16
EP1274339B1 (en) 2011-06-08
JP2003532460A (en) 2003-11-05
ATE511784T1 (en) 2011-06-15
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US20030158497A1 (en) 2003-08-21
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