WO2025062048A1 - Method, computer program and system for determining a pupillary light reflex of a person - Google Patents

Method, computer program and system for determining a pupillary light reflex of a person Download PDF

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Publication number
WO2025062048A1
WO2025062048A1 PCT/EP2024/076696 EP2024076696W WO2025062048A1 WO 2025062048 A1 WO2025062048 A1 WO 2025062048A1 EP 2024076696 W EP2024076696 W EP 2024076696W WO 2025062048 A1 WO2025062048 A1 WO 2025062048A1
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Prior art keywords
stimulus
person
stimuli
pupil size
periods
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PCT/EP2024/076696
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French (fr)
Inventor
Mathias ABEGG
Dominik BRÜGGER
Thomas FERRAZZINI
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Universität Bern
Machinemd Ag
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Publication of WO2025062048A1 publication Critical patent/WO2025062048A1/en

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    • 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

Definitions

  • the present invention relates to a method for determining a pupillary light reflex of a person, a computer program for determining a pupillary light reflex of a person as well as to a system for determining a pupillary light reflex of a person.
  • the pupillary light reflex an involuntary response of the pupil to light stimuli, serves as a crucial diagnostic indicator in various medical fields, including neurology, ophthalmology, and optometry. It reflects the integrity of the visual pathway and the autonomic nervous system, making it an essential tool in assessing neurological conditions, detecting optic nerve disorders, and evaluating overall ocular health.
  • This task is solved by a method for determining a pupillary light reflex of a person with the features of claim 1 , a computer program for determining a pupillary light reflex of a person according to claim 20 as well as a system for determining a pupillary light reflex of a person according to claim 21.
  • a first aspect of the invention relates to a method, particularly a computer-implemented method, for determining a pupillary light reflex of a person.
  • the method comprises exposing at least one eye of the person to a series of stimuli comprising a first stimulus and a second stimulus, wherein the first stimulus and the second stimulus are displayed in an alternating fashion.
  • the second stimulus is displayed for increasing periods, wherein for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus and the second stimulus, a change of a pupil size of the person in response to the alternation is detected.
  • the pupillary light reflex of the person is determined from the detected changes in pupil size.
  • the term “period” denotes a duration of time of a single cycle of display of a respective stimulus, such as the first or the second stimulus, during the alternating displaying of the first and the second stimulus.
  • the increasing periods of the second stimulus allow to dynamically investigate the pupillary light reflex of the person as a function of the period of the second stimulus, which provides valuable information for the sensory and motor functions of the eye, particularly for the assessment of the integrity of the retinal, pigment epithelium and choroid. These structures represent the starting point of the pupillary pathway.
  • the second stimulus is preferably different from the first stimulus.
  • the second stimulus is different from the first stimulus by means of different light conditions associated with the second stimulus compared to light conditions associated with the first stimulus, such that the alternating displaying between the first stimulus and the second stimulus causes a pupillary light reflex of the person in response to the alternation. Examples for different light conditions of the first stimulus compared to the second stimulus can be found in the following.
  • the first stimulus comprises a first luminosity that is higher than a second luminosity of the second stimulus.
  • the first luminosity of the first stimulus is at least 2 times higher than the second luminosity of the second stimulus.
  • the first luminosity is between 10 lux and 1000 lux and the second luminosity is between 0 lux and 100 lux, preferably with the first luminosity being larger than the second luminosity.
  • the first luminosity of the first stimulus can be comparable to ambient luminosity, particularly comparable to the luminosity of an illuminated room, e.g. 50 lux to 1000 lux, such that the time required for the pupil of the person to adapt to the light conditions of the first stimulus is advantageously reduced, as the first stimulus essentially represents room light conditions.
  • the series of stimuli can be initiated with the first stimulus being displayed before the second stimulus.
  • the luminosity represents a parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
  • the first stimulus comprises a different color than the second stimulus.
  • the color likewise represents a parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
  • the first luminosity of the first stimulus and the second luminosity of the second stimulus differ by less than 10%, particularly wherein the first stimulus and the second stimulus comprise the same luminosity.
  • the first and the second stimulus preferably differ by another parameter than the luminosity that can trigger a pupillary light reflex.
  • the first stimulus comprises a different color than the second color.
  • the first and the second stimulus can be isoluminant stimuli that comprise different colors that have essentially the same luminosity.
  • the first stimulus and/or the second stimulus are devoid of contrasts or the first luminosity and the second luminosity are spatially homogeneous within the first and/or the second stimulus, respectively.
  • the first stimulus can be a white area displayed in a visual field of the person and the second stimulus can be a black area displayed in the visual field of the person.
  • Spatially homogeneous luminosities or stimuli that are devoid of contrasts allow for a quantification of the light conditions associated with the first and/or the second stimulus, which allows for a quantitative analysis of the pupillary light reflex.
  • the first stimulus and/or the second stimulus cover a majority of the visual field of the person, particularly the entire visual field of the person.
  • the first stimulus can be white and cover between 50% and 100% of the visual field, particularly 60%, 70%, 80%, 90% or 95% of the visual field of the person.
  • the second stimulus can be black and cover between 50% and 100% of the visual field, particularly 60%, 70%, 80%, 90% or 95% of the visual field of the person.
  • the remaining areas of the visual field can comprise contrasts.
  • Stimuli covering the majority of the visual field of the person typically cause a stronger pupillary light reflex, i.e. larger changes of the pupil size, compared to smaller stimuli. This measure thus increases the resolution of the pupillary light reflex in terms of the changes in pupil size.
  • contrasts can also be part of the displayed stimuli, particularly the first stimulus and the second stimulus.
  • the contrasts can be used to keep the gaze direction of the person in the area of the contrasts, which simplifies the detection of changes in pupil size in response to the alternating stimuli.
  • the contrasts are arranged in a central region of the visual field, such that the attention and in consequence the gaze direction of the person remains in the central region during the display of the series of stimuli.
  • the first and the second stimulus differ in their display areas in which they are displayed in the visual field of the person.
  • the display area can be understood as a portion of the visual field of the person.
  • the second stimulus is displayed in a larger display area, particularly a 2-10 times larger area than the first stimulus or vice versa.
  • the display area represents another parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
  • At least some periods of the second stimulus are shorter than a period of the first stimulus. This measure particularly allows to investigate the dynamics of the pupillary light reflex, in particular the dynamics of the dilatation of the pupil, as a function of the increasing periods of the second stimulus, wherein after each period of the second stimulus, the pupil of the person is reset to a constricted state in the longer periods of the first stimulus.
  • At least 20%, at least 30%, at least 40%, at least 60%, at least 70%, at least 80%, or at least 90% of the periods of the second stimulus, or all periods of the second stimulus are shorter than a period of the first stimulus, particularly wherein said period of the first stimulus does not vary by more than 50% or wherein said period of the first stimulus remains constant during the series of stimuli.
  • the first stimulus is displayed for periods of constant duration, particularly for constant durations between 1s and 15s.
  • These constant durations are typically long enough for the pupil of the person to dilate to a dilated state with a maximum pupil size or to constrict to a fully constricted state with a minimum pupil size during the display of the first stimulus, depending on the light conditions of the first stimulus with respect to the second stimulus.
  • the pupil sizes are thus comparable for all alternations, such that the pupillary light reflex in response to the alternation can be consistently determined by means of changes of the pupil size with respect to the same reference size of the pupil.
  • the pupillary light reflex can be determined in a time-saving manner, typically within a few minutes, while delivering reliable results due to the determination of changes of the pupil size with respect to said reference size of the pupil obtained from the first stimulus being displayed for a constant duration.
  • the periods of the second stimulus increase from a first duration to a second duration, wherein the first duration is longer than 1 % of a period of the first stimulus, and wherein the second duration is shorter than 2 times of a period of the first stimulus.
  • the increase of the duration between two consecutively displayed second stimuli is in increments between 0.05s and 0.3s.
  • the increase of the duration between two consecutively displayed second stimuli defines a temporal resolution of the detected changes in pupil size in dependence of the period of the second stimulus.
  • the first and the second stimulus are alternated between 10 and 100 times.
  • the first stimulus comprises a higher first luminosity than a second luminosity of the second stimulus and the first stimulus is displayed for constant periods of 3s, wherein the period of the second stimulus is increased from 100ms to 5s in increments of 100ms for every alternation.
  • the change of pupil size is, particularly for each alternation, determined from a difference between a maximum pupil size and a minimum pupil size, wherein the maximum pupil size is determined during display of the first stimulus upon an alternation from the second stimulus to the first stimulus and wherein the minimum pupil size is determined from a minimum size of the pupil detected upon the alternation during display of the first stimulus or the subsequently displayed second stimulus. Determining the maximum pupil size during display of the first stimulus upon the alternation from the second stimulus to the first stimulus ensures that the determined maximum pupil size is associated with a maximum dilatation of the pupil that can be reached in the respective period of the second stimulus displayed immediately before the alternation from the second stimulus to the first stimulus.
  • Determining the minimum pupil size from a minimum size of the pupil detected upon the alternation during display of the first stimulus or the subsequently displayed second stimulus displayed subsequently after the period of the first stimulus, in which the maximum pupil size has been determined ensures that the determined minimum pupil size is associated with a minimum dilatation of the pupil that can be reached by exposing the eye to the respective period of the first stimulus.
  • a pupil size change rate is determined, particularly wherein the pupil size change rate is determined in a time interval between said maximum pupil size and said minimum pupil size, wherein the pupillary light reflex of the person is further determined from the determined pupil size change rate.
  • the pupil size change rate corresponds to a slope of datapoints corresponding to the detected pupil sizes with respect to the time upon alternation.
  • the pupil size change rate is determined by a plurality of pupil sizes determined in a time sequence in response to the alternation.
  • the person upon the series of stimuli, the person is exposed to a further series of stimuli, wherein for the further series of stimuli, the first stimulus and the second stimulus are displayed in an alternating fashion, wherein the first stimulus comprises a first luminosity that is higher than a second luminosity of the second stimulus, and wherein in the course of the alternating displaying, the second stimulus is displayed for increasing periods, wherein the periods of the second stimulus are longer than the periods of the first stimulus.
  • the further series of stimuli delivers additional information on the pupillary light reflex of the person for substantially larger time scales of the second stimulus, compared to the time scales of the second stimulus used in the series of stimuli.
  • only one eye of the person at a time is exposed to the series of stimuli, such that only the pupillary light reflex elicited by one eye is determined, wherein the respective other eye is continuously exposed to the second stimulus or a luminosity below 100 lux, particularly below 10 lux, more particularly a luminosity of 0 lux.
  • the pupillary light reflex of the person is determined for a first eye of the person while keeping the second eye of the person at a constant luminosity, whereafter the pupillary light reflex of the person is determined for the second eye of the person while keeping the first eye of the person at a constant luminosity.
  • the constant luminosity may particularly correspond to the luminosity of the second stimulus or a luminosity below 100 lux particularly below 10 lux, more particularly a luminosity of 0.
  • a respective luminosity of the first stimulus and/or the second stimulus is kept constant or is varied by less than 1 log unit, particularly less than 0.5 log unit, more particularly less than 0.25 log unit.
  • the first stimulus remains identical and/or the second stimulus remains identical.
  • the periods between two consecutively displayed second stimuli become longer.
  • a sampling frequency corresponding to the inverse of the periods between two consecutively displayed second stimuli decreases in the course of the series of stimuli.
  • the pupillary light reflex can be sampled at a higher sampling frequency at the beginning of the series, where the pupillary light reflex induced by short periods of the second stimulus is typically very pronounced, and at a lower sampling frequency toward the end of the series, where the pupillary light reflex typically enters a saturation regime for long second stimuli. This measure thus reduces a total time of the series of stimuli while still delivering accurate information regarding the pupillary light reflex.
  • the periods between two consecutively displayed second stimuli are constant, whereafter in a second part of the series (10) of stimuli, the periods between two consecutively displayed second stimuli become longer.
  • This measure allows for a sampling at equal periods of the second stimulus in the first part at the beginning of the series, in order to thoroughly investigate the dynamic of the pupillary light reflex in this regime and to lower the sampling frequency in the second part toward the end of the series, where the pupillary light reflex enters said saturation regime.
  • a second aspect of the invention relates to a computer program for determining a pupillary light reflex of a person.
  • the computer program comprises instructions which, when the program is executed by a computer, cause the computer to: cause an optical device to:
  • the computer is configured to execute the computer-implemented steps of the method according to the first aspect of the invention.
  • the embodiments of the first aspect of the invention can therefore also be applied to the second aspect of the invention.
  • a third aspect of the invention relates to a system for determining a pupillary light reflex of a person, wherein the system comprises: an optical device configured to:
  • system according to the third aspect of the invention comprises the computer according to the second aspect of the invention, which is configured to execute the computer- implemented steps of the method according to the first aspect of the invention
  • the embodiments of the first aspect of the invention can also be applied to the third aspect of the invention.
  • the optical device of the system according to the third aspect of the invention is integrated in goggles, particularly in a head-mounted display to be worn by a person.
  • the computer may or may not be integrated in the goggles.
  • the optical device can receive data indicative of commands of the computer that cause the optical device to generate the series of stimuli and communicate with the computer by sending data indicative of the detected changes of pupil sizes of the person to the computer, such that the computer can determine the pupillary reflex of the person.
  • the optical device and the computer can communicate for example via cable-based communication means. If the computer is not integrated in the goggles, the optical device and the computer can communicate via wired or wireless communication means.
  • data indicative of the detected changes of pupil sizes of the person can be sent to a server or a cloud for determination of the pupillary reflex of the person by means of the cloud or the server.
  • the system according to third aspect of the invention particularly allows to determine the pupillary light reflex independently of educated medical personnel and independent of medical infrastructure.
  • the computer program can be executed on conventional goggles, particularly conventional augmented and/or virtual reality goggles such as head-mounted displays, which are becoming increasingly popular for home use.
  • Fig. 1a, b show a first stimulus and a second stimulus in a visual field of a person, according to an embodiment of the invention (a) as well as an exemplary series of stimuli (b) according to an embodiment of the invention;
  • Fig. 3 shows a generic change of pupil size as a function of increasing periods of the second stimulus, representing the pupillary light reflex according to an embodiment of the invention
  • Fig. 4 shows a system for determining a pupillary light reflex of a person, according to an embodiment of the invention.
  • Fig. 1a shows a first stimulus 11 and a second stimulus 12 in a visual field 1 of a person, according to an embodiment of the invention.
  • the first stimulus 11 and the second stimulus 12 differ by their luminosity.
  • the first stimulus 11 is white and the second stimulus 12 is black.
  • the first stimulus 11 and the second stimulus 12 are each displayed such that the first stimulus 11 and the second stimulus 12 cover the entire visual field 1 of a person. This may be done for example by placing the person, particularly her eyes, sufficiently close to a screen on which the stimuli 11 ,12 are displayed, particularly by using goggles with an integrated display to be worn by the person, for example as shown in Fig. 4. Displaying the stimuli 11 ,12 over the entire visual field 1 of the person increases the pupillary light reflex of the person when the first and the second stimulus 11 ,12 are displayed in an alternating fashion, as shown for example in Fig. 1 b.
  • the first stimulus 11 may comprise contrasts, particularly contrasts arranged in a central region of the visual field 1 , which typically causes the person to maintain her gaze direction in the central region of the visual field. This measure simplifies the determination of the pupillary light reflex. However, preferably, for the first stimulus 11 , a majority of the visual field 1 of the person is devoid of contrasts.
  • the alternating displaying between the first and the second stimulus 11 ,12 is shown by means of a series 10 of alternating first and second stimuli 11 ,12, according to an embodiment of the invention. At least one eye of the person is exposed to the series 10 of alternating first and second stimuli 11 ,12, wherein in the course of the alternating displaying, the second stimulus 12 is displayed for increasing periods.
  • the series 10 of first and second stimuli 11 ,12 begins with a white first stimulus
  • the period of the second stimulus 12 is increased by a constant amount of 100ms, wherein the period of the first stimulus 11 remains constant at 3s.
  • the first and the second stimulus 11 ,12 are alternated 50 times, such that the last second stimulus 12 of the series 10 is displayed for 5s.
  • the increasing periods of the black, second stimulus 12 allow to dynamically investigate the pupillary light reflex of the person as a function of the period of the second stimulus 12, which provides valuable information about the sensory functions of the eye.
  • the person is exposed to a further series of stimuli.
  • the further series of stimuli corresponds to the series 10 of stimuli, wherein the periods of the second stimulus 12 used for the further series are all longer than the periods of the first stimulus
  • the second stimulus 12 may be displayed for periods increasing from 7s to 15s, while the first stimulus 11 is still displayed for constant periods, for example for 3s in the present embodiment.
  • the further series of stimuli delivers additional information on the pupillary light reflex of the person for substantially larger time scales of the second stimulus
  • Fig. 2 shows generic changes of a pupil size upon an alternation from the second stimulus 12 to the first stimulus 11 for increasing periods of the second stimulus 12, according to an embodiment of the invention.
  • the change may be induced particularly by different luminosities and/or by different colors of the first stimulus 11 and the second stimulus 12.
  • the first stimulus 11 comprises a higher luminosity than the second stimulus 12, as in the embodiment of Figs. 1a, b.
  • the x-axis of the plot shown in Fig. 2 depicts a time measured with respect to an alternation from the second stimulus 12 to the first stimulus 11 and the y-axis shows a pupil size of the person.
  • the exemplary generic lines are plotted to illustrate the effect of increasing periods of the second stimulus 12 on the pupil size: the longer the period of the second stimulus 12, the larger the pupil size at the time of the alternation, which is a consequence of the increasing dark periods that cause the pupil to dilate.
  • the pupil size decreases towards essentially the same size for all periods of the second stimulus 12, which reflects the size of the pupil under steady light conditions corresponding to the first stimulus 11.
  • the change in pupil size upon alternation from the second stimulus 12 to the first stimulus 11 for increasing periods of the second stimulus 12 thus provides time- resolved information of the pupillary light reflex of the person.
  • a reaction time delay between the alternation and a change of the pupillary size represents another parameter that can be used to determine the pupillary light reflex.
  • the decrease of the pupil size from its dilated size at the time of the alternation to its constricted state corresponding to steady light conditions of the first stimulus 11 occurs on the milliseconds-scale, particularly within 200ms. 7
  • the change in pupil size can for example be determined by means of a maximum pupil size and a minimum pupil size detected during displaying of the first stimulus 11 following each period of the second stimulus 12, such that every period of the second stimulus 12 is associated with an amplitude value representing the change of pupil size.
  • the amplitude value corresponds to the change of pupil size, particularly to a difference between the maximum pupil size and the minimum pupil size. This information can be used to quantify the pupillary light reflex of the person, for example as shown in Fig. 3.
  • a pupil size change rate can be determined in response to the alternation.
  • the pupil size change rate additionally comprises time-resolved information of the pupil size upon an alternation from the second stimulus 12 to the first stimulus 11 , associated with each period of the second stimulus 12.
  • the pupil size change rate comprises a set of pupil size values with associated time values upon the alternation that represent the dynamic, time-resolved change of the pupil size for each period of the second stimulus 12, particularly between the maximum pupil size and the minimum pupil size.
  • Fig. 3 shows a generic change of the pupil size of a person as a function of increasing periods of the second stimulus 12.
  • the changes of the pupil size for different periods of the second stimulus 12 can for example be obtained from the embodiments of Fig. 1 and 2.
  • the change of pupil size of the person first increases with the period of the second stimulus 12, reflecting the increasing exposure times of the eye of the person to the second stimulus 12 that cause the pupil to increasingly dilate.
  • the change of the pupil size generically approximates a plateau for periods of the second stimulus 12 that are so long that at the time of the alternation, the pupil of the person has reached a state of maximum dilatation and does barely dilate further for increasing periods of the second stimulus 12.
  • the pupillary light reflex of the person can be quantified.
  • the pupillary light reflex is quantified by identifying a duration of the period of the second stimuli 12 that is associated with the onset of an approximated plateau. This time can be indicative of the pupillary light reflex and be used to assess the integrity or health of the eye. plateau.
  • the onset of the plateau regime can be quantified for example by means of a predetermined derivative value of the change of the pupil size with respect to the period of the second stimulus 12. If the derivative value of the change of the pupil size falls below said predetermined derivative value, this is an indication for the onset of the plateau.
  • the pupillary light reflex is quantified by means of a plateau amplitude A p that is associated with said maximum dilatation of the pupil.
  • the dynamics of the increasing change of the pupil size from short periods of the second stimulus 12 a plateau duration t p of the second stimulus 12 can deliver additional information on the pupillary light reflex.
  • the periods of the second stimulus 12 do not need to be increased until a plateau in the detected change of pupil size is obtained to determine the pupillary light reflex.
  • the pupillary light reflex may also be determined by means of a slope of the change of the pupil size for periods of the second stimulus 12 before the onset of the plateau.
  • the method for determining a pupillary light reflex of a person according to the present invention can be applied to multiple persons to identify persons with an abnormal pupillary light reflex.
  • the detected pupil sizes are preferably normalized for each person, for example to a maximum or a minimum pupil size (corresponding to the dilated or the constricted state of the pupil, respectively) of each person determined after exposing the person to a sufficiently long second stimulus 12 or first stimulus 11 , that results in a maximum or minimum pupil size that can be reached by the person.
  • Persons with abnormal pupillary light reflex can be identified for example by means of deviations of their individual plateau duration t p and/or their individual plateau amplitude A p compared to average values of the plateau duration t p and/or the plateau amplitude A p obtained from averaging over multiple persons. Assuming a sufficiently large group of people with a large proportion of whom having a normal pupillary light reflex, stronger deviations indicate a higher probability of an abnormal pupillary light reflex compared to smaller deviations.
  • Fig. 4 shows a system 100 for determining a pupillary light reflex of a person according to an embodiment of the invention.
  • the system 100 comprises a computer 20 as well as an optical device 30 that are, according to the present embodiment, integrated in or on the goggles 40 to be worn by the person.
  • the optical device 30 is configured to generate said series 10 of stimuli comprising the first stimulus 11 and the second stimulus 12, for example as shown in Fig.1 , wherein the first stimulus 11 and the second stimulus 12 are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus 12 is displayed for increasing periods.
  • the stimuli are displayed such to the person that they are arranged in the visual field 1 of the person defined by the eyes 2a, 2b of the person.
  • Fig. 4 depicts the first stimulus 11 displayed to the person by means of a white stimulus that covers the entire visual field 1 of the left eye 2a of the person.
  • the right eye 2b of the person may or may not be exposed to the stimuli.
  • first one of the eyes 2a, 2b of the person may be exposed to the series 10 of stimuli, whereafter the other of the two eyes 2b, 2a of the person is exposed to the series 10 of stimuli, so as to determine the pupillary light reflex for both eyes 2a, 2b of the person separately.
  • the optical device 30 is further configured to detect for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus 11 and the second stimulus 12 a change of a pupil size of the person in response to the alternation.
  • the changes of pupil sizes detected by the optical device 30 are processed by the computer 20 in order to determine the pupillary light reflex of the person, for example according to the embodiment of Fig. 3.
  • the system 100 particularly allows to determine the pupillary light reflex independently of educated medical personnel and independent of medical infrastructure.
  • the computer program can be executed on conventional goggles, particularly conventional augmented and/or virtual reality goggles used for entertainment purposes, which are becoming increasingly popular for home use.
  • Optical device 30 Goggles 40

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Abstract

The invention relates to a method, particularly a computer-implemented method, for determining a pupillary light reflex of a person, wherein the method comprises exposing at least one eye of the person to a series of stimuli comprising a first stimulus (11) and a second stimulus (12), wherein the first stimulus (11) and the second stimulus (12) are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus (12) is displayed for increasing periods, wherein for at least some alternations of a plurality of alternations between the first stimulus (11) and the second stimulus (12), a change of a pupil size of the person in response to the alternation is detected, and wherein the pupillary light reflex of the person is determined from the detected changes in pupil size. The invention further relates to a computer program for determining a pupillary light reflex of a person as well as a system (100) for determining a pupillary light reflex of a person.

Description

Method, computer program and system for determining a pupillary light reflex of a person
Description:
The present invention relates to a method for determining a pupillary light reflex of a person, a computer program for determining a pupillary light reflex of a person as well as to a system for determining a pupillary light reflex of a person.
The pupillary light reflex, an involuntary response of the pupil to light stimuli, serves as a crucial diagnostic indicator in various medical fields, including neurology, ophthalmology, and optometry. It reflects the integrity of the visual pathway and the autonomic nervous system, making it an essential tool in assessing neurological conditions, detecting optic nerve disorders, and evaluating overall ocular health.
Traditional methods for measuring the pupillary light reflex often involve manual and subjective assessments, which can lead to inconsistencies and errors in the results. More advanced methods using predefined and automatized method protocols have improved these assessments, yet they typically require a lot of time, which is perceived as disadvantageous by persons to be tested for their pupillary reflex or even leads to measurement errors due to distraction and/or fatigue of the person. Additionally, conventional methods usually require specialized equipment and skilled personnel, making them impractical for widespread use and limiting their application in non-clinical settings.
Based on this, it is subject of the present invention to provide a method for determining a pupillary light reflex of a person, a computer program for determining a pupillary light reflex of a person as well as a system for determining a pupillary light reflex of a person that allow for a reliable, time-efficient determination of the pupillary light reflex without requiring specialized equipment and personnel. It is also subject of the present invention that this particular pupillary light reflex can be used to assess the integrity of the retina, pigment epithelium and choroid. These structures represent the starting point of the pupillary pathway.
This task is solved by a method for determining a pupillary light reflex of a person with the features of claim 1 , a computer program for determining a pupillary light reflex of a person according to claim 20 as well as a system for determining a pupillary light reflex of a person according to claim 21.
Advantageous embodiments of the invention are given in the corresponding dependent claims and described in the following.
A first aspect of the invention relates to a method, particularly a computer-implemented method, for determining a pupillary light reflex of a person. The method comprises exposing at least one eye of the person to a series of stimuli comprising a first stimulus and a second stimulus, wherein the first stimulus and the second stimulus are displayed in an alternating fashion. In the course of the alternating displaying, the second stimulus is displayed for increasing periods, wherein for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus and the second stimulus, a change of a pupil size of the person in response to the alternation is detected. The pupillary light reflex of the person is determined from the detected changes in pupil size.
In the context of the present invention, the term “period” denotes a duration of time of a single cycle of display of a respective stimulus, such as the first or the second stimulus, during the alternating displaying of the first and the second stimulus.
The increasing periods of the second stimulus allow to dynamically investigate the pupillary light reflex of the person as a function of the period of the second stimulus, which provides valuable information for the sensory and motor functions of the eye, particularly for the assessment of the integrity of the retinal, pigment epithelium and choroid. These structures represent the starting point of the pupillary pathway.
The second stimulus is preferably different from the first stimulus. In particular, the second stimulus is different from the first stimulus by means of different light conditions associated with the second stimulus compared to light conditions associated with the first stimulus, such that the alternating displaying between the first stimulus and the second stimulus causes a pupillary light reflex of the person in response to the alternation. Examples for different light conditions of the first stimulus compared to the second stimulus can be found in the following.
According to an embodiment of the invention, the first stimulus comprises a first luminosity that is higher than a second luminosity of the second stimulus.
For example, the first luminosity of the first stimulus is at least 2 times higher than the second luminosity of the second stimulus.
For example, the first luminosity is between 10 lux and 1000 lux and the second luminosity is between 0 lux and 100 lux, preferably with the first luminosity being larger than the second luminosity.
The first luminosity of the first stimulus can be comparable to ambient luminosity, particularly comparable to the luminosity of an illuminated room, e.g. 50 lux to 1000 lux, such that the time required for the pupil of the person to adapt to the light conditions of the first stimulus is advantageously reduced, as the first stimulus essentially represents room light conditions. The series of stimuli can be initiated with the first stimulus being displayed before the second stimulus. As such, the luminosity represents a parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
In another embodiment of the invention, the first stimulus comprises a different color than the second stimulus.
The color likewise represents a parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
According to an embodiment of the invention, the first luminosity of the first stimulus and the second luminosity of the second stimulus differ by less than 10%, particularly wherein the first stimulus and the second stimulus comprise the same luminosity. If the first luminosity of the first stimulus and the second luminosity of the second stimulus differ by less than 10%, the first and the second stimulus preferably differ by another parameter than the luminosity that can trigger a pupillary light reflex. For example, if the luminosity of the first stimulus and the luminosity of the second stimulus differ by less than 10%, particularly wherein the first stimulus and the second stimulus comprise the same luminosity, the first stimulus comprises a different color than the second color. In other words, the first and the second stimulus can be isoluminant stimuli that comprise different colors that have essentially the same luminosity.
According to another embodiment of the invention, the first stimulus and/or the second stimulus are devoid of contrasts or the first luminosity and the second luminosity are spatially homogeneous within the first and/or the second stimulus, respectively. For example, the first stimulus can be a white area displayed in a visual field of the person and the second stimulus can be a black area displayed in the visual field of the person. Spatially homogeneous luminosities or stimuli that are devoid of contrasts allow for a quantification of the light conditions associated with the first and/or the second stimulus, which allows for a quantitative analysis of the pupillary light reflex.
In another embodiment, the first stimulus and/or the second stimulus cover a majority of the visual field of the person, particularly the entire visual field of the person. For example, the first stimulus can be white and cover between 50% and 100% of the visual field, particularly 60%, 70%, 80%, 90% or 95% of the visual field of the person. The second stimulus can be black and cover between 50% and 100% of the visual field, particularly 60%, 70%, 80%, 90% or 95% of the visual field of the person. The remaining areas of the visual field can comprise contrasts. Stimuli covering the majority of the visual field of the person typically cause a stronger pupillary light reflex, i.e. larger changes of the pupil size, compared to smaller stimuli. This measure thus increases the resolution of the pupillary light reflex in terms of the changes in pupil size.
However, contrasts can also be part of the displayed stimuli, particularly the first stimulus and the second stimulus. The contrasts can be used to keep the gaze direction of the person in the area of the contrasts, which simplifies the detection of changes in pupil size in response to the alternating stimuli. For example, the contrasts are arranged in a central region of the visual field, such that the attention and in consequence the gaze direction of the person remains in the central region during the display of the series of stimuli.
Particularly, the first and the second stimulus differ in their display areas in which they are displayed in the visual field of the person. The display area can be understood as a portion of the visual field of the person. For example, the second stimulus is displayed in a larger display area, particularly a 2-10 times larger area than the first stimulus or vice versa. The display area represents another parameter to induce different light conditions associated with the first stimulus compared to the second stimulus, which in turn can trigger a pupillary light reflex.
In an embodiment of the invention, at least some periods of the second stimulus are shorter than a period of the first stimulus. This measure particularly allows to investigate the dynamics of the pupillary light reflex, in particular the dynamics of the dilatation of the pupil, as a function of the increasing periods of the second stimulus, wherein after each period of the second stimulus, the pupil of the person is reset to a constricted state in the longer periods of the first stimulus.
In particular, at least 20%, at least 30%, at least 40%, at least 60%, at least 70%, at least 80%, or at least 90% of the periods of the second stimulus, or all periods of the second stimulus are shorter than a period of the first stimulus, particularly wherein said period of the first stimulus does not vary by more than 50% or wherein said period of the first stimulus remains constant during the series of stimuli.
In another embodiment of the invention, the first stimulus is displayed for periods of constant duration, particularly for constant durations between 1s and 15s. These constant durations are typically long enough for the pupil of the person to dilate to a dilated state with a maximum pupil size or to constrict to a fully constricted state with a minimum pupil size during the display of the first stimulus, depending on the light conditions of the first stimulus with respect to the second stimulus. At the time of the alternations from the first stimulus to the second stimulus, the pupil sizes are thus comparable for all alternations, such that the pupillary light reflex in response to the alternation can be consistently determined by means of changes of the pupil size with respect to the same reference size of the pupil. In particular, at least some periods of the second stimulus are shorter than a period of the first stimulus, wherein the first stimulus is displayed for periods of constant duration, particularly for constant durations between 1s and 15s. Consequently, the pupillary light reflex can be determined in a time-saving manner, typically within a few minutes, while delivering reliable results due to the determination of changes of the pupil size with respect to said reference size of the pupil obtained from the first stimulus being displayed for a constant duration.
For example, the periods of the second stimulus increase from a first duration to a second duration, wherein the first duration is longer than 1 % of a period of the first stimulus, and wherein the second duration is shorter than 2 times of a period of the first stimulus.
Particularly, the increase of the duration between two consecutively displayed second stimuli is in increments between 0.05s and 0.3s. The increase of the duration between two consecutively displayed second stimuli defines a temporal resolution of the detected changes in pupil size in dependence of the period of the second stimulus.
In an embodiment of the invention, for the series of stimuli, the first and the second stimulus are alternated between 10 and 100 times.
In an example, the first stimulus comprises a higher first luminosity than a second luminosity of the second stimulus and the first stimulus is displayed for constant periods of 3s, wherein the period of the second stimulus is increased from 100ms to 5s in increments of 100ms for every alternation.
In an embodiment of the invention, the change of pupil size is, particularly for each alternation, determined from a difference between a maximum pupil size and a minimum pupil size, wherein the maximum pupil size is determined during display of the first stimulus upon an alternation from the second stimulus to the first stimulus and wherein the minimum pupil size is determined from a minimum size of the pupil detected upon the alternation during display of the first stimulus or the subsequently displayed second stimulus. Determining the maximum pupil size during display of the first stimulus upon the alternation from the second stimulus to the first stimulus ensures that the determined maximum pupil size is associated with a maximum dilatation of the pupil that can be reached in the respective period of the second stimulus displayed immediately before the alternation from the second stimulus to the first stimulus. Determining the minimum pupil size from a minimum size of the pupil detected upon the alternation during display of the first stimulus or the subsequently displayed second stimulus displayed subsequently after the period of the first stimulus, in which the maximum pupil size has been determined, ensures that the determined minimum pupil size is associated with a minimum dilatation of the pupil that can be reached by exposing the eye to the respective period of the first stimulus. According to yet another embodiment of the invention, in response to the alternation, particularly to each alternation, a pupil size change rate is determined, particularly wherein the pupil size change rate is determined in a time interval between said maximum pupil size and said minimum pupil size, wherein the pupillary light reflex of the person is further determined from the determined pupil size change rate. The pupil size change rate corresponds to a slope of datapoints corresponding to the detected pupil sizes with respect to the time upon alternation.
In an embodiment of the invention, the pupil size change rate is determined by a plurality of pupil sizes determined in a time sequence in response to the alternation.
According to another embodiment of the invention, upon the series of stimuli, the person is exposed to a further series of stimuli, wherein for the further series of stimuli, the first stimulus and the second stimulus are displayed in an alternating fashion, wherein the first stimulus comprises a first luminosity that is higher than a second luminosity of the second stimulus, and wherein in the course of the alternating displaying, the second stimulus is displayed for increasing periods, wherein the periods of the second stimulus are longer than the periods of the first stimulus. As such, the further series of stimuli delivers additional information on the pupillary light reflex of the person for substantially larger time scales of the second stimulus, compared to the time scales of the second stimulus used in the series of stimuli.
In yet another embodiment of the invention, only one eye of the person at a time is exposed to the series of stimuli, such that only the pupillary light reflex elicited by one eye is determined, wherein the respective other eye is continuously exposed to the second stimulus or a luminosity below 100 lux, particularly below 10 lux, more particularly a luminosity of 0 lux.
In particular, the pupillary light reflex of the person is determined for a first eye of the person while keeping the second eye of the person at a constant luminosity, whereafter the pupillary light reflex of the person is determined for the second eye of the person while keeping the first eye of the person at a constant luminosity. The constant luminosity may particularly correspond to the luminosity of the second stimulus or a luminosity below 100 lux particularly below 10 lux, more particularly a luminosity of 0.
According to another embodiment of the invention, during the series of stimuli, a respective luminosity of the first stimulus and/or the second stimulus is kept constant or is varied by less than 1 log unit, particularly less than 0.5 log unit, more particularly less than 0.25 log unit.
In another embodiment of the invention, during the series of stimuli, the first stimulus remains identical and/or the second stimulus remains identical.
Keeping the respective luminosity of the first stimulus and/or the second stimulus constant, varying their luminosity within the stated limits or keeping the first stimulus and/or the second stimulus identical contributes to a meaningful detection of said change of the pupil size in response to the alternation, as a function of mainly or only the period of the second stimulus. In other words, these measures keep components of the detected pupil changes that are not related to the mere increase of the period of the second stimulus low, which improves the reliability of the method.
The embodiments that provide keeping the respective luminosity of the first stimulus and/or the second stimulus constant, varying them within the stated limits or keeping the first stimulus and/or the second stimulus identical underline an interpretation of an “alternating” display between the first stimulus and the second stimulus according to the invention in the sense that the first stimulus and the second stimulus each do not change or do not change substantially during the series of stimuli.
In an embodiment of the invention, in the course of the series of stimuli, the periods between two consecutively displayed second stimuli become longer. In other words, a sampling frequency corresponding to the inverse of the periods between two consecutively displayed second stimuli decreases in the course of the series of stimuli. As such, the pupillary light reflex can be sampled at a higher sampling frequency at the beginning of the series, where the pupillary light reflex induced by short periods of the second stimulus is typically very pronounced, and at a lower sampling frequency toward the end of the series, where the pupillary light reflex typically enters a saturation regime for long second stimuli. This measure thus reduces a total time of the series of stimuli while still delivering accurate information regarding the pupillary light reflex.
Particularly, during a first part of the series of stimuli, the periods between two consecutively displayed second stimuli are constant, whereafter in a second part of the series (10) of stimuli, the periods between two consecutively displayed second stimuli become longer. This measure allows for a sampling at equal periods of the second stimulus in the first part at the beginning of the series, in order to thoroughly investigate the dynamic of the pupillary light reflex in this regime and to lower the sampling frequency in the second part toward the end of the series, where the pupillary light reflex enters said saturation regime.
Particularly, the periods between two consecutively displayed second stimuli become longer once the detected pupil size change rate decreases. The pupil size change rate indicates a measure of the dynamic of the pupillary light reflex, such that it can be taken as a quantity to determine at which point of the series of stimuli the periods of the second stimulus can be increased without losing important information on the pupillary light reflex. A second aspect of the invention relates to a computer program for determining a pupillary light reflex of a person. The computer program comprises instructions which, when the program is executed by a computer, cause the computer to: cause an optical device to:
• generate a series of stimuli comprising a first stimulus and a second stimulus, wherein the first stimulus and the second stimulus are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus is displayed for increasing periods
• detect for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus and the second stimulus a change of a pupil size of the person in response to the alternation determine the pupillary light reflex of the person from the detected changes in pupil size.
In other words, the computer is configured to execute the computer-implemented steps of the method according to the first aspect of the invention. The embodiments of the first aspect of the invention can therefore also be applied to the second aspect of the invention.
A third aspect of the invention relates to a system for determining a pupillary light reflex of a person, wherein the system comprises: an optical device configured to:
• generate a series of stimuli comprising a first stimulus and a second stimulus, wherein the first stimulus and the second stimulus are displayed in an alternating fashion, wherein in the course of the alternating displaying, the second stimulus is displayed for increasing periods,
• detect for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus and the second stimulus a change of a pupil size of the person in response to the alternation and the computer according to the second aspect of the invention.
Since the system according to the third aspect of the invention comprises the computer according to the second aspect of the invention, which is configured to execute the computer- implemented steps of the method according to the first aspect of the invention, the embodiments of the first aspect of the invention can also be applied to the third aspect of the invention.
Particularly, the optical device of the system according to the third aspect of the invention is integrated in goggles, particularly in a head-mounted display to be worn by a person. The computer may or may not be integrated in the goggles. The optical device can receive data indicative of commands of the computer that cause the optical device to generate the series of stimuli and communicate with the computer by sending data indicative of the detected changes of pupil sizes of the person to the computer, such that the computer can determine the pupillary reflex of the person.
To this end, if the computer is integrated in the goggles, the optical device and the computer can communicate for example via cable-based communication means. If the computer is not integrated in the goggles, the optical device and the computer can communicate via wired or wireless communication means.
In particular, data indicative of the detected changes of pupil sizes of the person can be sent to a server or a cloud for determination of the pupillary reflex of the person by means of the cloud or the server.
The system according to third aspect of the invention particularly allows to determine the pupillary light reflex independently of educated medical personnel and independent of medical infrastructure. For example, the computer program can be executed on conventional goggles, particularly conventional augmented and/or virtual reality goggles such as head-mounted displays, which are becoming increasingly popular for home use.
Exemplary embodiments are described below in conjunction with the Figures. The Figures are appended to the claims and are accompanied by text explaining individual features of the shown embodiments and aspects of the present invention. Each individual feature shown in the Figures and/or mentioned in the text of the Figures may be incorporated (also in an isolated fashion) into a claim relating to the first aspect, the second aspect and/or the third aspect according to the present invention.
Fig. 1a, b show a first stimulus and a second stimulus in a visual field of a person, according to an embodiment of the invention (a) as well as an exemplary series of stimuli (b) according to an embodiment of the invention;
Fig. 2 shows a generic time-dependent change of a pupil size of a person upon an alternation from the second stimulus to the first stimulus for increasing periods of the second stimulus, according to an embodiment of the invention;
Fig. 3 shows a generic change of pupil size as a function of increasing periods of the second stimulus, representing the pupillary light reflex according to an embodiment of the invention; and Fig. 4 shows a system for determining a pupillary light reflex of a person, according to an embodiment of the invention.
Fig. 1a shows a first stimulus 11 and a second stimulus 12 in a visual field 1 of a person, according to an embodiment of the invention. According to the present embodiment, the first stimulus 11 and the second stimulus 12 differ by their luminosity. The first stimulus 11 is white and the second stimulus 12 is black. The first stimulus 11 and the second stimulus 12 are each displayed such that the first stimulus 11 and the second stimulus 12 cover the entire visual field 1 of a person. This may be done for example by placing the person, particularly her eyes, sufficiently close to a screen on which the stimuli 11 ,12 are displayed, particularly by using goggles with an integrated display to be worn by the person, for example as shown in Fig. 4. Displaying the stimuli 11 ,12 over the entire visual field 1 of the person increases the pupillary light reflex of the person when the first and the second stimulus 11 ,12 are displayed in an alternating fashion, as shown for example in Fig. 1 b.
Optionally, the first stimulus 11 may comprise contrasts, particularly contrasts arranged in a central region of the visual field 1 , which typically causes the person to maintain her gaze direction in the central region of the visual field. This measure simplifies the determination of the pupillary light reflex. However, preferably, for the first stimulus 11 , a majority of the visual field 1 of the person is devoid of contrasts.
In Fig. 1b, the alternating displaying between the first and the second stimulus 11 ,12 is shown by means of a series 10 of alternating first and second stimuli 11 ,12, according to an embodiment of the invention. At least one eye of the person is exposed to the series 10 of alternating first and second stimuli 11 ,12, wherein in the course of the alternating displaying, the second stimulus 12 is displayed for increasing periods. According to the present embodiment, the series 10 of first and second stimuli 11 ,12 begins with a white first stimulus
11 to be displayed for 3s, before a black second stimulus 12 is displayed for 100ms. Subsequently, the first stimulus 11 is displayed again for 3s, whereafter the second stimulus
12 is displayed for 200ms. For every following alternation between the first stimulus 11 and the second stimulus 12, the period of the second stimulus 12 is increased by a constant amount of 100ms, wherein the period of the first stimulus 11 remains constant at 3s. The first and the second stimulus 11 ,12 are alternated 50 times, such that the last second stimulus 12 of the series 10 is displayed for 5s. The increasing periods of the black, second stimulus 12 allow to dynamically investigate the pupillary light reflex of the person as a function of the period of the second stimulus 12, which provides valuable information about the sensory functions of the eye. Optionally, upon the series 10 of stimuli, the person is exposed to a further series of stimuli. The further series of stimuli corresponds to the series 10 of stimuli, wherein the periods of the second stimulus 12 used for the further series are all longer than the periods of the first stimulus
11. In contrast, in the series 10 of stimuli according to the present example, some periods of the second stimulus 12 are shorter than the first stimulus 11 (cf. the first two second stimuli 12 of Fig. 1b with periods of 100ms and 200ms compared to the period of 3s of the first stimulus 11) while other periods of the second stimulus 12 are longer than the first stimulus 11 (cf. the last second stimulus 12 of Fig. 1 b with a period of 5s). For example, for the further series of stimuli, the second stimulus 12 may be displayed for periods increasing from 7s to 15s, while the first stimulus 11 is still displayed for constant periods, for example for 3s in the present embodiment. As such, the further series of stimuli delivers additional information on the pupillary light reflex of the person for substantially larger time scales of the second stimulus
12, compared to the time scales of the second stimulus 12 used in the series 10 of stimuli.
Fig. 2 shows generic changes of a pupil size upon an alternation from the second stimulus 12 to the first stimulus 11 for increasing periods of the second stimulus 12, according to an embodiment of the invention. The change may be induced particularly by different luminosities and/or by different colors of the first stimulus 11 and the second stimulus 12. In the present embodiment, the first stimulus 11 comprises a higher luminosity than the second stimulus 12, as in the embodiment of Figs. 1a, b.
The x-axis of the plot shown in Fig. 2 depicts a time measured with respect to an alternation from the second stimulus 12 to the first stimulus 11 and the y-axis shows a pupil size of the person. The exemplary generic lines are plotted to illustrate the effect of increasing periods of the second stimulus 12 on the pupil size: the longer the period of the second stimulus 12, the larger the pupil size at the time of the alternation, which is a consequence of the increasing dark periods that cause the pupil to dilate. Upon alternation and a reaction delay of the person, the pupil size decreases towards essentially the same size for all periods of the second stimulus 12, which reflects the size of the pupil under steady light conditions corresponding to the first stimulus 11. The change in pupil size upon alternation from the second stimulus 12 to the first stimulus 11 for increasing periods of the second stimulus 12 thus provides time- resolved information of the pupillary light reflex of the person. Besides the change in pupil size, a reaction time delay between the alternation and a change of the pupillary size represents another parameter that can be used to determine the pupillary light reflex. Typically, the decrease of the pupil size from its dilated size at the time of the alternation to its constricted state corresponding to steady light conditions of the first stimulus 11 occurs on the milliseconds-scale, particularly within 200ms. 7
The change in pupil size can for example be determined by means of a maximum pupil size and a minimum pupil size detected during displaying of the first stimulus 11 following each period of the second stimulus 12, such that every period of the second stimulus 12 is associated with an amplitude value representing the change of pupil size. The amplitude value corresponds to the change of pupil size, particularly to a difference between the maximum pupil size and the minimum pupil size. This information can be used to quantify the pupillary light reflex of the person, for example as shown in Fig. 3.
Moreover, besides an amplitude value, a pupil size change rate can be determined in response to the alternation. In excess to the amplitude value, the pupil size change rate additionally comprises time-resolved information of the pupil size upon an alternation from the second stimulus 12 to the first stimulus 11 , associated with each period of the second stimulus 12. For example, the pupil size change rate comprises a set of pupil size values with associated time values upon the alternation that represent the dynamic, time-resolved change of the pupil size for each period of the second stimulus 12, particularly between the maximum pupil size and the minimum pupil size.
Fig. 3 shows a generic change of the pupil size of a person as a function of increasing periods of the second stimulus 12. The changes of the pupil size for different periods of the second stimulus 12 can for example be obtained from the embodiments of Fig. 1 and 2. As a result, and as shown in the generic plot of Fig. 3, the change of pupil size of the person first increases with the period of the second stimulus 12, reflecting the increasing exposure times of the eye of the person to the second stimulus 12 that cause the pupil to increasingly dilate. However, the change of the pupil size generically approximates a plateau for periods of the second stimulus 12 that are so long that at the time of the alternation, the pupil of the person has reached a state of maximum dilatation and does barely dilate further for increasing periods of the second stimulus 12. From the changes of the pupil size as a function of the period of the second stimulus 12, the pupillary light reflex of the person can be quantified. For example, the pupillary light reflex is quantified by identifying a duration of the period of the second stimuli 12 that is associated with the onset of an approximated plateau. This time can be indicative of the pupillary light reflex and be used to assess the integrity or health of the eye. plateau. The onset of the plateau regime can be quantified for example by means of a predetermined derivative value of the change of the pupil size with respect to the period of the second stimulus 12. If the derivative value of the change of the pupil size falls below said predetermined derivative value, this is an indication for the onset of the plateau. Alternatively or additionally, the pupillary light reflex is quantified by means of a plateau amplitude Ap that is associated with said maximum dilatation of the pupil. Moreover, the dynamics of the increasing change of the pupil size from short periods of the second stimulus 12 a plateau duration tp of the second stimulus 12 can deliver additional information on the pupillary light reflex. However, the periods of the second stimulus 12 do not need to be increased until a plateau in the detected change of pupil size is obtained to determine the pupillary light reflex. The pupillary light reflex may also be determined by means of a slope of the change of the pupil size for periods of the second stimulus 12 before the onset of the plateau.
In particular, the method for determining a pupillary light reflex of a person according to the present invention can be applied to multiple persons to identify persons with an abnormal pupillary light reflex. To this end, for comparison of pupillary light reflexes of multiple persons, the detected pupil sizes are preferably normalized for each person, for example to a maximum or a minimum pupil size (corresponding to the dilated or the constricted state of the pupil, respectively) of each person determined after exposing the person to a sufficiently long second stimulus 12 or first stimulus 11 , that results in a maximum or minimum pupil size that can be reached by the person. Persons with abnormal pupillary light reflex can be identified for example by means of deviations of their individual plateau duration tp and/or their individual plateau amplitude Ap compared to average values of the plateau duration tp and/or the plateau amplitude Ap obtained from averaging over multiple persons. Assuming a sufficiently large group of people with a large proportion of whom having a normal pupillary light reflex, stronger deviations indicate a higher probability of an abnormal pupillary light reflex compared to smaller deviations.
Fig. 4 shows a system 100 for determining a pupillary light reflex of a person according to an embodiment of the invention. The system 100 comprises a computer 20 as well as an optical device 30 that are, according to the present embodiment, integrated in or on the goggles 40 to be worn by the person.
Based on instructions of a computer program executed by the computer 20, the optical device 30 is configured to generate said series 10 of stimuli comprising the first stimulus 11 and the second stimulus 12, for example as shown in Fig.1 , wherein the first stimulus 11 and the second stimulus 12 are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus 12 is displayed for increasing periods. The stimuli are displayed such to the person that they are arranged in the visual field 1 of the person defined by the eyes 2a, 2b of the person. By means of an example, Fig. 4 depicts the first stimulus 11 displayed to the person by means of a white stimulus that covers the entire visual field 1 of the left eye 2a of the person. The right eye 2b of the person may or may not be exposed to the stimuli. In particular, first one of the eyes 2a, 2b of the person may be exposed to the series 10 of stimuli, whereafter the other of the two eyes 2b, 2a of the person is exposed to the series 10 of stimuli, so as to determine the pupillary light reflex for both eyes 2a, 2b of the person separately. The optical device 30 is further configured to detect for at least some alternations, particularly for each alternation of a plurality of alternations between the first stimulus 11 and the second stimulus 12 a change of a pupil size of the person in response to the alternation. The changes of pupil sizes detected by the optical device 30 are processed by the computer 20 in order to determine the pupillary light reflex of the person, for example according to the embodiment of Fig. 3.
The system 100 according to the present embodiment particularly allows to determine the pupillary light reflex independently of educated medical personnel and independent of medical infrastructure. For example, the computer program can be executed on conventional goggles, particularly conventional augmented and/or virtual reality goggles used for entertainment purposes, which are becoming increasingly popular for home use.
List of reference signs
Visual field 1
Left eye 2 a
Right eye 2b Series of first and second stimuli 10
First stimulus 11
Second stimulus 12
Computer 20
Optical device 30 Goggles 40
System 100

Claims

Patent claims:
1. A method, particularly a computer-implemented method, for determining a pupillary light reflex of a person, wherein the method comprises exposing at least one eye of the person to a series (10) of stimuli comprising a first stimulus (11) and a second stimulus (12), wherein the first stimulus (11) and the second stimulus (12) are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus (12) is displayed for increasing periods, wherein for at least some alternations of a plurality of alternations between the first stimulus (11) and the second stimulus (12), a change of a pupil size of the person in response to the alternation is detected, and wherein the pupillary light reflex of the person is determined from the detected changes in pupil size.
2. The method according to claim 1 , wherein the first stimulus (11) comprises a first luminosity that is higher than a second luminosity of the second stimulus (12).
3. The method according to claim 1 or 2, wherein the first stimulus (11) comprises a different color than the second stimulus (12).
4. The method according to claim 3, wherein the luminosity of the first stimulus (11) and the luminosity of the second stimulus (12) differ by less than 10 %, particularly wherein the first stimulus (11) and the second stimulus (12) comprise the same luminosity.
5. The method according to one of the preceding claims, wherein at least some periods of the second stimulus (12) are shorter than a period of the first stimulus (11).
6. The method according to claim 5, wherein at least 20%, at least 30%, at least 40%, at least 60%, at least 70%, at least 80%, or at least 90% of the periods of the second stimulus (12), or all periods of the second stimulus (12) are shorter than the period of the first stimulus (11).
7. The method according to one of the preceding claims, wherein the first stimulus (11) is displayed for periods of constant duration, particularly for constant durations between 1s and 15s.
8. The method according to one of the preceding claims, wherein the periods of the second stimulus (12) increase from a first duration to a second duration, wherein the first duration is longer than 1% of a period of the first stimulus (11), and wherein the second duration is shorter than 2 times of a period of the first stimulus (11).
9. The method according to one of the preceding claims, wherein the change of pupil size is determined from a difference between a maximum pupil size and a minimum pupil size, wherein the maximum pupil size and the minimum pupil size are each determined upon an alternation from the second stimulus (12) to the first stimulus (11).
10. The method according to one of the preceding claims, wherein in response to the alternation, a pupil size change rate is determined, particularly wherein pupil size change rate is determined in a time interval between said maximum pupil size and said minimum pupil size, wherein the pupillary light reflex of the person is further determined from the determined pupil size change rate.
11. The method according to one of the preceding claims, wherein for the series (10) of stimuli, the first stimulus (11) is displayed before the second stimulus (12).
12. The method according to one of the preceding claims, wherein the first stimulus (11) and/or the second stimulus (12) are devoid of contrasts or wherein the first luminosity and/or the second luminosity are spatially homogeneous within the first and the second stimulus (11 ,12), respectively.
13. The method according to claim 12, wherein the first stimulus (11) and/or the second stimulus (12) cover a majority of a visual field (1) of the person, particularly the entire visual field (1) of the person.
14. The method according to one of the preceding claims, wherein upon the series (10) of stimuli, the person is exposed to a further series of stimuli, wherein for the further series of stimuli, the first stimulus (11) and the second stimulus (12) are displayed in an alternating fashion, wherein the first stimulus (11) comprises a first luminosity that is higher than a second luminosity of the second stimulus (12), and wherein in the course of the alternating displaying, the second stimulus (12) is displayed for increasing periods, wherein the periods of the second stimulus (12) are longer than the periods of the first stimulus (11).
15. The method according to one of the preceding claims, wherein during the series (10) of stimuli, a respective luminosity of the first stimulus (11) and/or the second stimulus (12) is kept constant or is varied by less than 1 log unit.
16. The method according to one of the preceding claims, wherein during the series (10) of stimuli, the first stimulus (11) remains identical and/or wherein the second stimulus (12) remains identical.
17. The method according to one of the preceding claims, wherein in the course of the series (10) of stimuli, the periods between two consecutively displayed second stimuli (12) become longer.
18. The method according to claim 17, wherein during a first part of the series (10) of stimuli, the periods between two consecutively displayed second stimuli (12) are constant, whereafter in a second part of the series (10) of stimuli, the periods between two consecutively displayed second stimuli (12) become longer.
19. The method according to claim 17 or 18 when referring to claim 10, wherein the periods between two consecutively displayed second stimuli (12) become longer once the detected pupil size change rate decreases.
20. A computer program comprising instructions which, when the program is executed by a computer (20), cause the computer to: cause an optical device (30) to:
• generate a series (10) of stimuli comprising a first stimulus (11) and a second stimulus (12), wherein the first stimulus (11) and the second stimulus (12) are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus (12) is displayed for increasing periods,
• detect for at least some alternations of a plurality of alternations between the first stimulus (11) and the second stimulus (12) a change of a pupil size of the person in response to the alternation determine the pupillary light reflex of the person from the detected changes in pupil size.
21. A system (100) for determining a pupillary light reflex of a person, wherein the system (100) comprises: an optical device (30) configured to: • generate a series (10) of stimuli comprising a first stimulus (11) and a second stimulus (12), wherein the first stimulus (11) and the second stimulus (12) are displayed in an alternating fashion, and wherein in the course of the alternating displaying, the second stimulus (12) is displayed for increasing periods,
• detect for at least some alternations of a plurality of alternations between the first stimulus (11) and the second stimulus (12) a change of a pupil size of the person in response to the alternation and the computer (20) according to claim 20.
PCT/EP2024/076696 2023-09-22 2024-09-23 Method, computer program and system for determining a pupillary light reflex of a person WO2025062048A1 (en)

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