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WO2024147767A1 - Appareil et procédé de détection précoce de maladie basée sur un réflexe pupillaire - Google Patents

Appareil et procédé de détection précoce de maladie basée sur un réflexe pupillaire Download PDF

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Publication number
WO2024147767A1
WO2024147767A1 PCT/TR2023/050008 TR2023050008W WO2024147767A1 WO 2024147767 A1 WO2024147767 A1 WO 2024147767A1 TR 2023050008 W TR2023050008 W TR 2023050008W WO 2024147767 A1 WO2024147767 A1 WO 2024147767A1
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WO
WIPO (PCT)
Prior art keywords
eye
camera
pupil
light source
visible light
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/TR2023/050008
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English (en)
Inventor
Hakan Urey
Abdullah KUCUKODUK
Afsun SAHIN
Hasan UREY
Ugur AYGUN
Arda GULERSOY
Firat TURKKAL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koc Universitesi
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Koc Universitesi
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Publication date
Application filed by Koc Universitesi filed Critical Koc Universitesi
Priority to PCT/TR2023/050008 priority Critical patent/WO2024147767A1/fr
Publication of WO2024147767A1 publication Critical patent/WO2024147767A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/113—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for determining or recording eye movement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/0016—Operational features thereof
    • A61B3/0033—Operational features thereof characterised by user input arrangements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/11—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for measuring interpupillary distance or diameter of pupils
    • A61B3/112—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for measuring interpupillary distance or diameter of pupils for measuring diameter of pupils
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/14—Arrangements specially adapted for eye photography

Definitions

  • Field of invention is ophthalmic devices for early detection of eye and neurological diseases.
  • Figure 2 shows the optical layout of the device
  • Figure 3 shows the optical layout of the device with a display to generate cognitive load.
  • the pupil light reflex is a constituent of non-visual light perception system, and is composed of three components: (i) an afferent sensory branch originating from the retina and carried through optic nerve fibers to a (ii) mesencephalic relay centers of pretectal olivary and Edinger-Westphal nuclei, which directs the reflex response stimuli for pupil constriction via (iii) efferent motor branches that are carried back to both eyes through oculomotor nerves.
  • the PLR arcade triggers a bilateral simultaneous pupil constriction with either unilateral or bilateral light stimulation of the eyes.
  • RAPD is the difference between the reactions of the eyes to the light stimuli which occurs due to a relative impairment of light perception among one of the afferent visual pathways. In people with RAPD, pupils constrict less or do not constrict when the stimuli is removed from one eye and directed to the other eye. It is important to distinguish RAPD from efferent pupil defect, which occurs due to impairment of efferent pathways of the PLR arcade.
  • PIPR post-illumination pupil response
  • Chromatic response is an important aspect in PLR.
  • the importance of multicolor input is better understood when considering the neural pathways from the retina where cone and rod photoreceptors reside to the brain. Cones are activated with chromatic light input and they get a better resolution of the frames that our eyes perceive, therefore abnormalities in the neural pathway can be related to wavelength of the light input.
  • chromatic pupillometry is a particular method that is related to chromatic pupillometry to assess the function of the inner retinal light perception that is mediated by melanopsin-dependent ipRGCs.
  • Pupil response parameters are calculated by processing recorded camera images individually. Latency of constriction, magnitude of change during pupil constriction and velocity of constriction were given for each color separately and for both eyes. The equations used for each are given respectively. latency where T pU pii is the time when the pupil maximum size is observed (i.e., constriction starts) after the LED is flashed (Tfiash). where the magnitude is calculated for each eye separately using resting pupil diameter (Drest) and constricted pupil diameter (D constricted) . For healthy eyes, magnitudes corresponding to both eyes are expected to be the same. where "Response is the total response time of the pupil from the dilated (Tdiiated) to the Constricted (Tconstricted) .
  • RAPD /MPD Scare
  • MagnitudeRight and Magnitudeieft represent the magnitude of pupil constriction in response to right and left eye stimulation, respectively.
  • RAPD is scored as the log based ratio of pupil constriction magnitude, velocity and latency of one eye that follows stimulation of right and left eyes, respectively.
  • a negative RAPD score indicated an afferent defect on the right eye. All RAPD scores were calculated for each eye separately.
  • Two main experiments for SFT were performed using different wavelengths of light stimuli. Subjects were examined under dimmed light after waiting for 3 minutes in a dark environment for preparation.
  • the duration of the light sources is set to 0.1 second right LED on, 2 second rest and 0.1 second left LED for 5 cycles (one cycle including right LED on, rest, left LED on and rest for a total time of 4.2 seconds).
  • the stimuli are introduced in various different colors. Between each trial the patient was given 1 minute to rest. Total duration of the whole experiment per participant was approximately 2 minutes.
  • PLR is a significant metric that indicates several ocular and systemic disorders.
  • Previous work relates PIPR response to Alzheimer’s disease or Parkinson’s disease.
  • the proposed method in this method investigates the PLR by means of varying intensity and wavelength, which can be configured to address these neurological diseases as well.
  • the proposed method can be used as a diagnosis-assisting device, and by integrating machine learning (e.g., deep learning) algorithms this instrument can be used as an initial screening tool for ophthalmologists.
  • a headset is proposed, which is capable of performing SFT using light input of different wavelengths. While pupil size detection algorithms are used, metrics are obtained through signal processing, which are helpful for the detection of the abnormalities. According to previous studies, there is an inverse correlation between glaucoma intensity and PIPR response.
  • Glaucoma Glaucoma
  • Amblyopia Optic neuritis / MS
  • Optic nerve tumor Optic nerve infections or inflammation
  • 3rd cranial nerve palsies Retinal detachment
  • Intraocular tumor Severe macular degeneration, Retinal infection, Alzheimer's, Autism, Brain tumors, Parkinson’s, and Traumatic optic neuropathy
  • Figure 1 demonstrates the headworn pupillary reflex and pupil movement measurement system.
  • Figure 2 demonstrates the layout of the system for pupillary reflex measurement and pupil movements.
  • System comprises a left eye camera (14a) and right eye camera (14b) that captures the corresponding eye videos.
  • IR light sources (11 ) are used to illuminate each eye, and visible light blocker (15) is placed in front of each camera (14) to block visible light that is used for eye stimulation.
  • a beam splitter (12) is used to allow users to focus real world objects during the measurement.
  • Visible light sources (13) are placed, in a way that no visible light leakage occurs between the two parts of the system.
  • IR light source (11 ) which has an emission spectra that is partly in the visible band is placed in front of the eye, and acts as an indicator light (25).
  • the brightness of the indicator light (25) is low enough that it doesn’t affect the pupillary reflexes.
  • Perceived location of the indicator light (25) can be tuned by placing different lenses (19) in front of the indicator light (25). Even without the lens (19), indicator light (25) can be seen without clear focus but sufficient for the purposes of some of the tests.
  • Figure 4 demonstrates the data acquisition and analysis flow chart.
  • the user determines the LED colors and brightness that is going to be used for stimulation, led on and off times, number of stimulation cycles, RAPD score threshold. Captured NIR images are processed to calculate pupil response parameters.
  • adaptive algorithms are used. After 1 st test with red or blue LED, a decision could be made based on the subject’s pupillary response, age, and risk factors for two eyes and the screening test can be terminated.
  • test could be performed quickly by starting with black, then turning on red, then blue, then white leds in sequence without any dark intervals in between, and then all the chromatic results can be obtained in a shorter duration, especially if the risk factors of the patient is determined to be low.
  • Figure 5 illustrates the pupil response upon light stimulation for different cases.
  • pupil size changes simultaneously for both of the eyes independent of the light stimulation direction.
  • pupils respond differently to light stimuli if there is a defect in parasympathetic (efferent) pathway or anterior visual (afferent) pathway.
  • Figure 6 demonstrates the different configurations of light stimulation patterns. Even though a monochromatic pupillary reflex test is enough to detect simple anomalies, chromatic pupillary response is important for the early detection of various diseases such as glaucoma. Furthermore light duration, brightness, combination of colors can be tuned before measurements.
  • Figure 7 demonstrates the graphical user interface of the system. Both eyes can be visualized in real time. Users can control all the parameters required for the measurement through a user interface. Results and scores can be displayed through the GUI.
  • Figure 8 demonstrates the pupil diameter of one eye with respect to time is plotted. Metrics used in calculation of pupil response parameters are visualized.
  • LAT Latency of constriction Range: Time of onset of constriction following initiation of the light stimulus.
  • ACV Constriction Velocity Range: Average velocity of how the pupil diameter is constricting measured in millimeters per second.
  • ADV Dilation Velocity Range: The average pupillary velocity when, after having reached the peak of constriction, the pupil tends to recover and to dilate back to the initial resting size, measured in millimeters per second.
  • T75 Time to reach 75% recovery Range: The time to reach 75% of the original baseline pupil diameter after the peak of the constriction.
  • a portable device for detecting pupillary reflexes comprising left eye camera (14a) and a right eye camera (14b), where each camera (14) includes a visible light blocker (15) to transmit near infrared light and block visible light, an IR light source (11 ) coupled with each camera (10), at least one visible light source (13), a processing unit (17), wherein NIR pupil dilations and constrictions of each eye are recorded by the camera (14) while different color LEDs selected from the at least one visible light source (13) are turned on and off.
  • each camera (14) includes a visible light blocker (15) to transmit near infrared light and block visible light, an IR light source (11 ) coupled with each camera (10), at least one visible light source (13), a processing unit (17), wherein NIR pupil dilations and constrictions of each eye are recorded by the camera (14) while different color LEDs selected from the at least one visible light source (13) are turned on and off.
  • the recorded camera images are processed using the processing unit (17) to calculate a set of the following pupil response parameters (20) in real-time for each eye in addition to eye movement parameters (21 ), such parameters including eye rotation, blinking, and saccades as detected by the processing unit (17).
  • adaptive and learning based algorithms are used to determine personalized test settings to adjust the visible light source (13) sequence, light on and off durations, number of cycles and total test duration.
  • a recommendation based on the pupil response parameters (20) and eye movement parameters (21 ) for the subjects such as healthy, high RAPD score, glaucoma risk, or other neurological conditions are generated.
  • the visible light source (13) includes an array of white, red, green, and blue high brightness LEDs.
  • the left eye camera (14a) and right eye camera (14b) and visible light sources (13) and infrared light source (13) are operated in synchronism according to an algorithm to facilitate the measurement of the pupil response parameters (20).
  • the infrared light source (11 ) has an emission spectra that is partly in the visible band and is configured to serve as the indicator light (25) for the viewer to focus while the device is under use.
  • the infrared light source (11 ) and the camera (14) are aligned to have the same optical axis using a beam splitter (12) and wherein a clarity map of the pupil, which is an indicator for density of cataracts, is obtained by a bright pupil reflection from the eye.
  • the inter pupillary distance (IPD) of the eyes are measured and the distance between the indicator light (25) for each are mechanically adjusted to allow for the viewer to fuse at different accommodation distances.
  • the light from each visible light source (13) for one eye is mechanically blocked by a light separator (16) and not visible to the other eye.
  • the visible light sources (13) and the IR light sources (11 ) are high brightness LEDs or laser light sources, which can be brightness controlled via software based adjustment by using predetermined calibrated settings or using the pupil response parameters (20).
  • the processing unit is connected wirelessly to a mobile phone or tablet and the test can be performed by the person wearing the device without requiring a specialist using a custom app.
  • the processing unit is connected via cable to a computer and a specialist conduct the test using a GUI and software on the computer.
  • the unit is a table top unit for use in the clinic by a specialist and includes its own computer and interactive test screen.
  • a display (18) is placed in front of the user to generate cognitive load by displaying different patterns during the measurement.
  • the invention further discloses a method for detecting pupillary reflexes by way of using left eye camera (14a) and a right eye camera (14b), where each camera (14) includes a visible light blocker (15) to transmit near infrared light and block visible light.
  • An IR light source (1 1 ) is coupled with each camera (10) and at least one visible light source (13) and a processing unit (17) are operated such that NIR pupil dilations and constrictions of each eye are recorded by the camera (14) while different color LEDs selected from the at least one visible light source (13) are turned on and off.
  • the recorded camera images are processed using the processing unit (17) to calculate a set of pupil response parameters (20) in real-time for each eye in addition to eye movement parameters (21 ), such parameters including eye rotation, blinking, and saccades as detected by the processing unit (17).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Human Computer Interaction (AREA)
  • Eye Examination Apparatus (AREA)

Abstract

La présente invention propose un dispositif portable pour détecter des réflexes pupillaires comprenant une caméra d'œil gauche (14a) et une caméra d'œil droit (14b), chaque caméra (14) comprenant un bloqueur de lumière visible (15) destiné à transmettre la lumière proche infrarouge et bloquer la lumière visible, une source de lumière IR (11) couplée à chaque caméra (14), au moins une source de lumière visible (13), une unité de traitement (17) dans laquelle des dilations de pupille NIR et des constrictions de chaque œil sont enregistrées par la caméra (14) tandis que différentes DEL de couleur sélectionnées parmi la ou les sources de lumière visible (13) sont allumées et éteintes.
PCT/TR2023/050008 2023-01-05 2023-01-05 Appareil et procédé de détection précoce de maladie basée sur un réflexe pupillaire Ceased WO2024147767A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/TR2023/050008 WO2024147767A1 (fr) 2023-01-05 2023-01-05 Appareil et procédé de détection précoce de maladie basée sur un réflexe pupillaire

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PCT/TR2023/050008 WO2024147767A1 (fr) 2023-01-05 2023-01-05 Appareil et procédé de détection précoce de maladie basée sur un réflexe pupillaire

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090213329A1 (en) * 2008-02-26 2009-08-27 Kandel Gillray L Evaluating pupillary responses to light stimuli
WO2016105284A1 (fr) * 2014-12-26 2016-06-30 Koc University Appareil pour générer un éclairage à faisceau cohérent
US20170007119A1 (en) * 2011-03-02 2017-01-12 Brien Holden Vision Diagnostics Inc. Systems, Methods, and Devices for Measuring Eye Movement and Pupil Response
US20220133212A1 (en) * 2013-01-25 2022-05-05 Wesley W.O. Krueger Systems and methods for observing eye and head information to measure ocular parameters and determine human health status
US20220296097A1 (en) * 2018-06-28 2022-09-22 Mordechay SAYAR System and method for monitoring pupillary light response

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090213329A1 (en) * 2008-02-26 2009-08-27 Kandel Gillray L Evaluating pupillary responses to light stimuli
US20170007119A1 (en) * 2011-03-02 2017-01-12 Brien Holden Vision Diagnostics Inc. Systems, Methods, and Devices for Measuring Eye Movement and Pupil Response
US20220133212A1 (en) * 2013-01-25 2022-05-05 Wesley W.O. Krueger Systems and methods for observing eye and head information to measure ocular parameters and determine human health status
WO2016105284A1 (fr) * 2014-12-26 2016-06-30 Koc University Appareil pour générer un éclairage à faisceau cohérent
US20220296097A1 (en) * 2018-06-28 2022-09-22 Mordechay SAYAR System and method for monitoring pupillary light response

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