Systems and methods for obtaining local spectra from the eye

Abstract

The present disclosure relates to a handheld device for probing a selected area of an eye fundus of a user to obtain at least one parameter related to a physiological condition of the user and a system comprising the handheld device. The present disclosure further relates to a method of acquiring an optical spectrum from a selected area of the eye fundus of a user using the handheld device of the present disclosure.

Description

[0001] P7521PC00

[0002] 1

[0003] Systems and methods for obtaining local spectra from the eye

[0004] The present disclosure relates to a handheld device for probing a selected area of the eye fundus of a user and a method of acquiring an optical spectrum associated with a selected area of the eye fundus of the user.

[0005] Background

[0006] The human eye provides a transparent optical path to blood vessels, nerve cells, nerve fibers, and other tissues, enabling a wide range of wavelengths to pass through for non-invasive examination. This property creates an opportunity for optical diagnostics, allowing for the analysis of physiological parameters without interference from surrounding tissues such as skin, which typically obstructs measurements in other parts of the body. By leveraging the eye’s optical transparency, it therefore becomes possible to access critical biomarkers for systemic health conditions.

[0007] Blood tests are widely used for identifying and diagnosing a broad range of diseases. Two highly prevalent examples are anaemia and diabetes mellitus, both of which can have severe consequences if left undiagnosed and untreated. Anaemia affects approximately 37% of pregnant women worldwide, increasing the risks of infections, fatigue, poor pregnancy outcomes, and cognitive impairment. Anaemia is defined as a low number of red blood cells and is typically diagnosed based on low haemoglobin concentrations in the blood. Normal haemoglobin levels are 14-17 g / dL in adult men and 12-15 g / dL in women. Levels below these thresholds indicate anaemia, which can typically be treated effectively if diagnosed early.

[0008] Diabetes mellitus impacts over 550 million people globally and is a leading cause of complications such as blindness, kidney failure, cardiovascular diseases, and lower limb amputations. The condition can be diagnosed and monitored by measuring the percentage of glycated haemoglobin (HbA1c) in the blood, which reflects average blood glucose levels over time. Normal HbA1c levels are around 5% in healthy individuals but can rise to 15% in patients with poorly controlled diabetes. Despite the availability of effective treatments, around 240 million people with diabetes remain undiagnosed, particularly in developing countries, highlighting the critical need for accessible diagnostic solutions.P7521PC00

[0009] 2

[0010] The current methods for diagnosing anaemia and diabetes rely mostly on laboratory blood tests. The reliance on access to laboratories makes such methods inaccessible in remote or resource-limited settings, reducing the likelihood of early diagnosis and intervention. Over the years, efforts have been made to develop non-invasive, handheld, and low-cost devices to meet these challenges. Technologies such as photospectroscopy and photoplethysmography have been applied to tissues like the palm, nailbed, and fingers. However, most of these technologies suffer from one or more of the following limitations: challenging data collection methods; complex data analysis and feature extraction processes; affordability and portability; and relatively low accuracy (2021 An et al). The aforementioned sites that are applied for the analysis are partially-opaque and diffusive tissues that vary a lot from one individual to the other. Thus, current technologies are challenged by reduced signal-to-noise ratio (SNR) and by the difficulty of standardizing and normalizing the measurements.

[0011] The invention disclosed her addresses said challenges and describes methods and systems to overcome them, yielding a non-invasive, hand-held, multiple-use and low-cost device that would not require any dedicated infra-structure nor disposables. By analyzing the spectra of light reflected or re-emitted from selected locations in the eye fundus, physiological data such as haemoglobin concentration, oxygen saturation, and glycated haemoglobin percentage can be obtained. This provides an alternative to traditional blood tests, enabling non-invasive detection and monitoring of conditions such as anaemia and diabetes mellitus without the need for a dedicated infrastructure.

[0012] Furthermore, the methods and systems for spectral analysis that are provided by the present invention, together with an intuitive user interface for self-operation, ensure consistent and accurate measurements and make it suitable for use in remote places, primary care clinics, as well as in societies with limited resources and underserved populations.

[0013] It is therefore an objective of the present disclosure to provide a handheld multiple-use device and a method for spectral analysis of the eye fundus, enabling non-invasive and cost-effective diagnostic tests. The invention aims to address the limitations of current diagnostic tools, offering a user-friendly and accessible solution for early detection and monitoring of systemic health conditions such as anaemia and diabetes mellitus.P7521PC00

[0014] 3

[0015] Summary

[0016] Considering the prior art described above, it is an object of the present invention to provide a handheld device and a method which uses the handheld device for measuring an optical spectrum associated with a selected area of the eye fundus of a user, thus enabling reliable data acquisition. The present invention further aims to address the challenges of user alignment, device portability, and cost-effectiveness by incorporating automated adjustment mechanisms, compact design, and user-friendly interfaces suitable for self-operated applications. This solution allows for improved spectral measurement precision and broader accessibility for routine health monitoring and diagnostic purposes, even in remote, underserved locations.

[0017] The present disclosure therefore relates to a handheld device for probing a selected area of the eye fundus of a user, preferably to obtain at least one parameter related to a physiological condition of the user, the handheld device comprising: a housing integrated with: an eyecup for the eye of the user, an adjustment mechanism for adjusting a position and / or an orientation of the eyecup, a sensor configured to output a signal indicative of the position and / or orientation of the eyecup, a light source and a light detector, a gaze fixation target, an optical system comprising optical elements configured to: image the gaze fixation target onto a retina of the user, direct light emitted from the light source onto the selected area of the eye fundus of the user, and direct light returning from the eye fundus to the light detector; and, preferably, wherein the position of the gaze fixation target relative to the optical system is adjustable based on the signal from the sensor to ensure that the selected area of the eye fundus is illuminated by light which is emitted from the light source and directed into the eye fundus by the optical system.

[0018] The present disclosure further relates to a system comprising the handheld device according to the present disclosure, the system further comprising: a remote control unit in electronic communication with the handheld device. Preferably, the remote control unit is configured to perform one or more of the following: activate the device to perform spectral analysis, receive data collected by the light detector and perform a spectral analysis of said collected data, and output feedback based on the spectral analysis which is indicative of a physiological condition of the user.P7521PC00

[0019] 4

[0020] The present disclosure further relates to the use of a handheld device according to the present disclosure to obtain an optical spectrum associated with a selected area of the eye fundus of a user.

[0021] The present disclosure further relates to a method of acquiring an optical spectrum from a selected area of an eye fundus of a user, the method comprising: providing a handheld device or system according to the present disclosure, arranging the eye of the user within the eyecup of the handheld device and using the gaze fixation target to provide a visual aid to the user. Preferably, the position of the gaze fixation target is configured to ensure that an optical path of the light emitted from the light source and passing through the optical elements of the optical system of the handheld device is directed onto the selected area of the eye fundus of the user. Further, the method preferably uses the light source to emit light and the optical system to direct the light onto the selected area of the eye fundus of the user. The method further preferably directs, using the optical system, light returning from the eye into the light detector, and measures, using the light detector, the returning light to acquire an optical spectrum associated with the eye of the user.

[0022] With the presently disclosed solution, the handheld device ensures precise alignment with a desired eye fundus location through adjustments specifically designed to be intuitive and user-friendly, allowing for easy operation of the device or system. These adjustments streamline the optical alignment process, reducing user error and ensuring accurate measurements regardless of the user’s level of training. Furthermore, devices made in accordance with the present disclosure can be manufactured with compact and cost-efficient designs. This innovation empowers users to perform advanced spectral analysis within the eye fundus as an alternative to traditional blood testing, enabling timely diagnosis and monitoring of various health conditions while minimising dependence on specialised healthcare facilities and laboratories.

[0023] Description of the drawings

[0024] The present disclosure will in the following be described in greater detail with reference to the accompanying drawings. Various embodiments are described hereinafter with reference to the drawings. The drawings are examples of embodiments and are intended to illustrate some of the features of the presently disclosed solution, and are not limiting to the presently disclosed system and method.P7521PC00

[0025] 5

[0026] Fig. 1 a schematic view of internal components of an example handheld device

[0027] Fig. 2 a schematic view of the external components of an example handheld device

[0028] Fig. 3(a)-(c) schematic views illustrating the adjustment of the gaze fixation target on the digital screen relative to the position of the eyecups

[0029] Detailed description

[0030] The term “light source” used herein includes any arrangement of components capable of producing light, such as, but not limited to, single or multiple light-emitting diodes (LEDs) or laser diodes. The light source may also include optical components which manipulate the emitted light to achieve the desired functionalities as described below, such as, but not limited to, switching between continuous and pulse-mode operation or producing light in different wavelength ranges.

[0031] A preferred embodiment of the present disclosure relates to a handheld device for probing a selected area of the eye fundus of a user to obtain at least one parameter related to a physiological condition of the user, the handheld device comprising: a housing integrated with: an eyecup for the eye of the user, an adjustment mechanism for adjusting a position and / or an orientation of the eyecup, a sensor configured to output a signal indicative of the position and / or orientation of the eyecup, a light source and a light detector, a gaze fixation target, an optical system comprising optical elements configured to: image the gaze fixation target onto the retina of the user, direct light emitted from the light source onto the selected area of the eye fundus of the user, and direct light returning from the eye to the light detector; and, preferably, wherein the position of the gaze fixation target relative to the optical system is adjustable based on the signal to ensure that the selected area of the eye fundus is illuminated by light which is emitted from the light source and directed into the fundus of the eye by the optical system.

[0032] The present disclosure provides a handheld device designed to facilitate precise alignment of the optical system with the desired eye fundus area through user-friendly adjustments that accommodate varying distances between the eyes. The handheld device empowers users to perform advanced eye fundus spectral analysis with ease,P7521PC00

[0033] 6

[0034] ensuring accurate and reliable data acquisition. The integration of automated control allows users to operate the device while maintaining clinical standards equivalent to traditional blood testing, thus providing a non-invasive technique as alternative means of identifying diseases such as anaemia and diabetes.

[0035] Various implementations of the presently disclosed solution will now be described, each incorporating features that, while advantageous, are not essential to the functioning of the handheld device.

[0036] In some embodiments, the handheld device further comprises a control unit which is configured to receive an input signal associated with the signal outputted by the sensor; and, preferably, wherein the control unit is configured to adjust the position of the gaze fixation target relative to the optical system based on the received input signal to ensure that the selected area of the eye fundus is illuminated by light which is emitted from the light source and directed into the eye by the optical system.

[0037] In some embodiments, the handheld device comprises a screen configured to display the gaze fixation target. In some embodiments, the screen is an image display device, such as a digital display device, which displays the gaze fixation target, the control unit being configured to adjust the position of the gaze fixation target on the image display device by transmitting a control signal to the image display device. Preferably, the digital screen may operate in a resolution range that exceeds the resolution of the human eye, allowing users to clearly discern when the gaze fixation target is in focus.

[0038] In further embodiments, the screen and optical system are configured to position the gaze fixation target so that light emitted from the light source is directed onto an area within the eye of the user within a distance of 2 mm, such as within 5 mm, such as within 9 mm, from the center of vision (fovea) of the user’s eye. The position of the gaze fixation target may be adjusted on the screen to be imaged on the retina within the specified distance from the area that is illuminated by the light emitted from the light source for all operational positions and / or orientations of the eyecup.

[0039] The optical system may have an effective magnification factor X that allows the gaze fixation target to be imaged onto the retina within the specified distances from the area that is illuminated by the light emitted from the light source. In some implementations,P7521PC00

[0040] 7

[0041] the screen has a display area of at least 6·X2mm2, such as at least 30·X2mm2, such as at least 90·X2mm2(where X is the effective magnification factor of the optics), on which the gaze fixation target is capable of being displayed.

[0042] For example, for the gaze fixation target to support the illumination of two different areas on the retina of the user lying at a distance c / from each other, the display area of screen would need to encompass two display points at a distance of at least d multiplied by the magnification factor Xof the optical system. This ensures that the screen is sufficiently large to accommodate all gaze fixation target positions necessary for covering the areas of the retina within the specified distances from the fovea.

[0043] In some implementations, the digital screen may emit light in specific wavelength ranges, such as light at 580-630 nm, which is visible to the human eye, and at an intensity that minimally provokes contraction of a pupil of the eye of the user, e.g., in a range of from 0.5 Millilux to 2 Millilux, from 1 Millilux to 10 Millilux, from 10 Millilux to 50 Millilux, or from 10 Millilux to 100 Millilux.

[0044] In some embodiments, the screen is mechanically coupled to a motor which is configured to move the screen so as to adjust the position of the gaze fixation target.

[0045] Advantageously, the screen has a resolution of at least 200 / X pixels per mm, wherein X is an effective optical magnification of the optical system.

[0046] In some embodiments, the optical system has a fixed optical magnification. In other embodiments, the optical system has a tuneable optical magnification, and, optionally, wherein the optical magnification is controlled by the control unit.

[0047] In some embodiments, the shape of the gaze fixation target may facilitate clear differentiation between being in and out of focus. For example, in some embodiments, the gaze fixation target may have a shape, such as a six-arm star, which enhances its visibility and aids the user in maintaining alignment. Advantageously, the gaze fixation target may be sized to take up between 0.8 to 5 degrees of the field of view of a user. The gaze fixation target may take up between 0.24 times X mm to 1.5 times X mm of the screen, wherein X is an effective optical magnification of the optical system.P7521PC00

[0048] 8

[0049] In some embodiments, the handheld device comprises two eyecups. These eyecups may be configured to block external light, ensuring that ambient conditions do not cause user’s pupil contraction and do not interfere with the optical measurements. Preferably, the eyecups are made of an opaque material to ensure complete light isolation.

[0050] In some embodiments, the distance between the two eyecups is adjustable, allowing the user to position the eyecups to comfortably align with their eyes before taking any optical measurements. For example, the handheld device may include a slidable adjustment mechanism that enables the eyecups to be moved closer together or farther apart to accommodate different distances between the eyes of the user.

[0051] Alternatively, each eyecup can be connected to a common pivot by a respective pivot arm, said pivot arm being rotatable about the pivot around a pivot axis. The distance separating a center of each eyecup and a point along the pivot axis which is located on a rotation plane formed by the pivot arms rotating about the pivot axis may be greater than 21.5 mm, such as greater than 23 mm, such as greater than 25 mm, such as greater than 29 mm, such as greater than 31 mm, such as greater than 33 mm, such as greater than 35 mm, such as greater than 37 mm, such as greater than 39 mm, such as greater than 41 mm. Advantageously, this ensures that the distance between the two eyes of a user would be smaller than double the distance separating the center of each eyecup, and the eyecups would need to be rotated about the pivot axis until they would comfortably fit onto the two eyes of the user. This rotation inherently causes the device to adopt an angle between the two eyecups subtended from the pivot axis of less than 180 degrees, enabling the identification of whether the left or right eye is being measured based on the direction and magnitude of the rotation.

[0052] In some embodiments, the two pivot arms have a combined length of greater than 43 mm, such as greater than 46 mm, such as greater than 50 mm, such as greater than 58 mm, such as greater than 62 mm, such as greater than 66 mm, such as greater than 70 mm, such as greater than 74 mm, such as greater than 78 mm, such as greater than 82 mm.

[0053] In some embodiments, the housing is divided into two bodies, the two bodies being pivotably connected along the pivot axis and each eyecup being arranged on aP7521PC00

[0054] 9

[0055] respective body, an angle between the two bodies being adjustable so as to rotate the two eyecups about the pivot axis, and, optionally, the optical system is housed within one of the two bodies.

[0056] In some embodiments, the light emitted from the light source is prevented from entering one of the two eyecups, the other eyecup being accessible to light emitted by the light source and directed by the optical system so that the optical system is able to direct light into said other eyecup. The handheld device may further include a sensor, such as an accelerometer, configured to detect the tilt of the device. By determining whether the device is tilted upward or downward, the sensor can identify which eyecup is positioned to align with the user's left or right eye. This allows the system to accurately determine whether the left eye or the right eye is being measured based on the detected orientation — specifically, which eye is placed within the eyecup that is accessible to light emitted by the light source.

[0057] In some embodiments, the adjustment mechanism comprises the pivot, and, optionally, the two bodies of the housing, wherein the two bodies respectively form at least a part of each pivot arm.

[0058] In some embodiments, the rotation angle of the eyecups about the pivot axis is adjustable within a range of -43 degrees to 43 degrees, such as -42 degrees to 42 degrees, such as -40 degrees to 40 degrees, such as -38 degrees to 38 degrees, to accommodate a distance between the eyes of the user.

[0059] In some embodiments, the sensor is configured to output a signal indicative of an angle formed between the two eyecups subtending about the pivot, and wherein the control unit is configured to determine whether a left eye or a right eye of the user is positioned in the eyecup configured to receive light emitted from the light source based on the angle, and wherein the control unit is configured to adjust the position of the gaze fixation target based said determination. Advantageously, the use of the sensor allows for dynamic adjustment of the position of the gaze fixation target without the need for any user input. Moreover, this determination ensures that the gaze fixation target is appropriately aligned with respect to the selected eye fundus location for each eye. As the eye of the user will usually spontaneously align its fovea with the gaze fixation target, the optics, including the positioning of the light source relative to the screen andP7521PC00

[0060] 10

[0061] the fixation target on it, ensures that the illumination light spot is focused on the selected eye fundus location. In other words, the system achieves the correct alignment by imaging the fixation target onto the fovea while simultaneously directing the illuminating light source onto the desired fundus location, from which the spectrum is to be acquired.

[0062] In some embodiments, a rotation plane of the eyecups is divided into a first region corresponding to the user positioning their left eye in the eyecup configured to receive light emitted from the light source and a second region corresponding to the user positioning their right eye in the eyecup configured to receive light emitted from the light source, and wherein the control unit is configured to adjust the position of the gaze fixation target on the screen based on the eyecups being positioned within the first region or the second region.

[0063] In some embodiments, the control unit adjusts the position of the gaze fixation target by transmitting a command signal to the screen. The command transmitted by the control unit may be determined based on a known optical path of light emitted by the light source through the optical elements.

[0064] In some embodiments, the command signal transmitted by the control unit to the screen is determined at least partly based on a model of the optical path of light emitted by the light source through the optical elements of the optical system which is stored in a memory unit accessible to the control unit.

[0065] In some embodiments, the command transmitted by the control unit is further determined based on whether the left eye or right eye of the user is positioned within the eyecup configured to receive light emitted from the light source.

[0066] In some embodiments, the optical system comprises one or more lenses configured to focus light emitted from the light source onto the selected area of the eye fundus of the user.

[0067] In some embodiments, the optical system comprises one or more beam splitters and / or one or more reflective mirrors for directing light emitted from the light source into theP7521PC00

[0068] 11

[0069] eye of the user and / or reflected light from the retina of the eye of the user to the light detector.

[0070] Preferably, the optical elements are arranged such that light emitted by the light source and travelling towards the eye and light returning from the eye have a partially overlapping optical path.

[0071] In some embodiments, the light source is configured to emit light with a wavelength within the range of 400 nm to 850 nm. In other embodiments, the light source is configured to emit visible light and / or near-infrared light. Advantageously, in some embodiments, the light source is operable at different wavelengths and may comprise functionality for continuous or pulse-mode operation. For instance, the light source may emit a continuous beam of infrared light for readiness checks, while visible light may be emitted as a pulse during the spectrum acquisition process. This dual-mode functionality of the light source enhances the adaptability of the device to different stages of operation of the handheld device. In other implementations, the light source may comprise two different light sources that are separately used for continuous and pulse-mode operation rather than a single light source being used for both functionalities. The separate light sources may be switched on when they are required at different stages of operation of the device.

[0072] In some embodiments, the light source is operable at different wavelengths, such as at discrete wavelengths or across a continuous band of wavelengths.

[0073] In some embodiments, the light detector is configured to measure an intensity of light as a function of wavelength. This configuration allows for detailed spectral analysis, capturing specific optical signatures associated with physiological parameters.

[0074] In some embodiments, the handheld device further comprises a spectrophotometer which comprises the light detector. In some embodiments, the spectrophotometer may be a compact non-sequential spectrophotometer, typically based on a detector array, for example, diode array, CCD, or CMOS, in combination with, for example, a prism, grating, a linear variable filter, or a Fabry-Perot filter. In other embodiments, the spectrophotometer may be a Raman spectrophotometer.P7521PC00

[0075] 12

[0076] In some embodiments, the spectrophotometer may be activated by the control unit together with the activation of the light source, which may produce a light pulse. The spectrophotometer may measure / record the spectrum of a portion of the light beam that passes through an entrance slit to the spectrometer. In some implementations, the spectrum or spectra recorded by the spectrophotometer, along with data regarding the source intensity of the illumination beams, may be transferred to the control unit. The control unit may analyze the spectrum or spectra locally or transmit them wirelessly to an external device, such as a mobile phone with an appropriate application installed. The external device may display the results to the user and / or transmit them to a healthcare professional. Preferably, the spectrum or spectra may be compared to model data to verify whether they lie within the expected values. If the spectra fall outside the expected boundaries, such as due to large eye movement or a closed eyelid during acquisition, an indication may be provided to the control unit. This indication may trigger a repeat acquisition for the affected spectrum, with the newly acquired spectrum replacing the one that fell outside the expected boundaries.

[0077] In some embodiments, the control unit may be programmed to acquire a series of spectra with each user-triggered acquisition, such as by touching an activation button.

[0078] In some implementations, multiple spectra may be acquired under various conditions to ensure the reliability and accuracy of the data and to calculate physiological parameters. For example, spectra may be acquired from different locations within the eye or under different conditions, such as at different times in the cardiac cycle, to yield the data for obtaining a physiological parameter by spectral analysis.

[0079] In other examples, a first light pulse may be used to provoke eye accommodations, and the spectrum resulting from this pulse may be ignored in subsequent analysis. Multiple spectra may also be acquired under equal conditions to enhance the reliability of measurements. Advantageously, these modes of operation both increase the reliability of the acquired data and minimise the effect of uncontrolled and unwanted variations in the data.

[0080] In some embodiments, the control unit may adjust the position of the gaze fixation target to direct the light beam to different locations within the eye. For example, when measuring at the optic nerve head, the control unit may move the gaze fixation targetP7521PC00

[0081] 13

[0082] by a small increment, such as less than 1.0·X mm, such as less than 0.8·X mm, such as less than 0.6·X mm, such as less than 0.4·X mm, such as less than 0.2·X mm (where X is an effective optical magnification of the optical system), corresponding to two locations within the optic nerve head. Advantageously, the difference between any two of these selected locations is the volume of blood through which the light beam passes, while other factors remain effectively unchanged. By acquiring spectra at these two locations, it becomes possible to mathematically eliminate blood volume as an unknown variable and calculate physiological parameters, such as haemoglobin concentration. This can be also applied when acquiring spectra at the same location but at different timings within the cardiac cycle. While blood vessel pulsations inside the eye may not be as pronounced, this approach can theoretically yield improved data for estimating haemoglobin concentration.

[0083] In some embodiments, the control unit may be configured to acquire spectra at specific time intervals. For example, the control unit may acquire a spectrum between every 1 milliseconds to 1000 milliseconds, such as 10 milliseconds to 500 milliseconds, such as 20 milliseconds to 250 milliseconds, such as 40 milliseconds to 100 milliseconds, such as 50 milliseconds to 75 milliseconds. Advantageously, this may help to capture data corresponding to different pulsation states of blood vessels in the retina.

[0084] Moreover, this timing may also ensure that at least one spectrum is acquired close to the diastolic state and another close to the systolic state, allowing for an enhanced analysis of blood-related parameters.

[0085] In some implementations, the first spectrum acquired during a series of acquired spectra may be excluded from analysis if it triggers a reaction in the user’s eye, such as slight pupil contraction. By excluding the first spectrum and adding at least one additional spectrum to the series, the system ensures that subsequent measurements are taken under stabilised and consistent conditions, thereby improving the accuracy and reliability of the data for analysis. This approach also minimises the influence of transient artifacts, enabling a more precise characterisation of the desired parameters.

[0086] In some embodiments, the control unit is further configured to adjust the position of the gaze fixation target to measure optical spectra from multiple locations on the retina. This functionality may be used to create a grid of measurement points for comprehensive retinal analysis.P7521PC00

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[0088] In some embodiments, the control unit is configured to derive physiological information from the optical spectra, and, optionally, the physiological information comprises haemoglobin concentration, glycated haemoglobin percentage, and oxygen saturation.

[0089] In some embodiments, the eyecup(s) is / are made of an opaque material to block external light and, optionally, wherein the eyecup(s) is / are adjustable to fit different user anatomies.

[0090] In some embodiments, the optical elements comprise one or more polarisers and / or one or more beam splitters.

[0091] In some embodiments, at least one optical element is configured to block specular reflections from the surface of the eye from entering the light detector. The polariser(s) may be configured to block unwanted specular reflections, enhancing the signal-to-noise ratio of the detected spectra.

[0092] In some embodiments, the handheld device comprises an aperture positioned between the eyecup(s) and the light detector which is configured to block specular reflections from the surface of the eye from entering the light detector.

[0093] In some embodiments, the control unit is configured to adjust the position of the gaze fixation target on the screen to direct the light emitted from the light source onto an optic nerve head of the eye of the user, and optionally, the adjustment is based on a standard model of the eye stored in memory accessible to the control unit.

[0094] In some embodiments, the handheld device further comprises a focusing adjustment mechanism, such as a knob, allowing the user to optimise the focus of the gaze fixation target.

[0095] In some embodiments, the focusing adjustment mechanism is configured to adjust the position of the screen or one or more of the optical elements to allow the user to optimise the focus of the gaze fixation target.

[0096] In some embodiments, upon rotation of the knob the position of the gaze fixation target is configured to move relative to the optical elements of the optical system.P7521PC00

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[0098] In some embodiments, the optical system is configured to create a light spot within the eye fundus, the light spot being a focused region of illumination targeting the selected area in the fundus of the eye of the user for spectral analysis.

[0099] In some embodiments, the light spot has a diameter of less than 1 mm, such as less than 0.8 mm, such as less than 0.6 mm, such as less than 0.4 mm, such as less than 0.2 mm.

[0100] In some embodiments, the eyecups comprise a measurement eyecup and an inactive eyecup, the measurement eyecup being configured to receive light emitted from the light source, and the inactive eyecup being configured to not receive light emitted from the light source.

[0101] Another preferred embodiment of the present disclosure relates to a system comprising the handheld device according to the present disclosure, the system further comprising:

[0102] a remote control unit in electronic communication with the handheld device and configured to perform one or more of the following: activate the device to perform spectral analysis, receive data collected by the light detector and perform a spectral analysis of said collected data, and output feedback based on the spectral analysis which is indicative of a physiological condition of the user. Advantageously, the remote control unit may enable advanced data processing and storage capabilities, facilitating cloud-based analysis and remote monitoring by healthcare providers.

[0103] Another preferred embodiment of the present disclosure relates to the use of a handheld device according to the present disclosure or the system according to the present disclosure to obtain an optical spectrum from a selected area in the fundus of an eye of a user.

[0104] In some embodiments, the optical spectrum is used for diagnosing one or more physiological conditions, wherein the physiological conditions are selected from the group comprising: anaemia, diabetes mellitus, age-related macular degeneration, diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease, retinal vascular diseases, and glaucoma.

[0105] In some embodiments, the handheld device is used for monitoring a percentage of glycated haemoglobin in the blood of a user.P7521PC00

[0106] 16

[0107] A further preferred embodiment of the present disclosure relates to a method of acquiring an optical spectrum associated with a selected area in the eye fundus of a user, the method comprising: a) providing a handheld device according to the present disclosure b) arranging the eye of the user within the eyecup of the handheld device, c) using the gaze fixation target to provide a visual aid to the user, the position of the gaze fixation target being configured to ensure that an optical path of the light emitted from the light source and passing through the optical elements of the optical system of the handheld device is directed onto the selected area of the fundus of the eye of the user, d) using the light source to emit light and the optical system to direct the light onto the selected area of the eye fundus of the user, e) directing, using the optical system, light returning from the eye into the light detector, f) measuring, using the light detector, the returning light to acquire an optical spectrum associated with the eye of the user.

[0108] Preferably, the sequence of steps d) to f) leading to the acquisition of spectral data can be designed to take less than 100 milliseconds. This is approximately half the typical time it takes for a human to react to an introduced stimulus with eye movement, also known as the saccadic reaction time (see e.g., 1997 Gezeck et al.). By ensuring that the sequence is completed within this time frame, the method minimises the potential for errors caused by involuntary eye movements during spectral acquisition.

[0109] In some embodiments, the selected area is an optic nerve head in the eye.

[0110] Advantageously, the optic nerve head is rich in blood vessels but relatively poor in light-sensitive nerve cells compared to the rest of the retina. These characteristics result in a dominant spectral signature of blood in the acquired spectra. Additionally, the user barely senses the light used to obtain these spectra, which minimises extra eye movements and reduces the influence on pupil contraction, thereby enhancing the accuracy and reliability of the measurements.

[0111] In some embodiments, the method comprises repeating steps c) to f) so as to measure optical spectra from at least two different locations, such as at a grid of different locations within the selected area, wherein between measurements the position of the gaze fixation target is adjusted by the control unit to ensure that the light emitted by the light source is focused by the optical elements on a different location.P7521PC00

[0112] 17

[0113] For instance, spectra acquired from locations spaced, for example, 2 mm apart around the center of vision (fovea) can be used for the assessment and monitoring of various retinal and systemic conditions. The grid-based spectral acquisition allows for the evaluation of progressive degeneration of ganglion cells, which characterises glaucoma, and the identification of the accumulation of drusen and pigmentation changes associated with age-related macular degeneration (AMD). It can also detect microaneurysms, retinal hemorrhages, and vascular abnormalities that are linked to diabetic retinopathy (DR). Furthermore, it enables the analysis of changes in tissue oxygen saturation, which are associated with glaucoma, and the identification of biomarkers linked to certain neurological diseases such as Parkinson’s disease and Alzheimer’s disease, as demonstrated in recent studies (e.g., 2023 Lapointe et al.).

[0114] In some embodiments, the method further comprising the steps of: adjusting, using the adjustment mechanism, the position and / or orientation of the eyecup, outputting, using the sensor, a signal indicative of the position and / or orientation of the eyecup, transmitting the signal to the control unit, and adjusting, using the control unit, the position of the gaze fixation target relative to the optical system based on the received signal.

[0115] In some embodiments, the method further comprises repeating steps c) to f) so as to measure optical spectra at different stages during the cardiac cycle.

[0116] In some embodiments, the method further comprises adjusting the position and / or orientation of the eyecup(s) relative to the housing to accommodate the distance between the eyes of the user.

[0117] In some embodiments, the method further comprises detecting a rotational position of the eyecup(s) about the pivot axis using the sensor, transmitting the detected position to the control unit, and setting or adjusting the position of the gaze fixation target to ensure optical alignment of the light emitted by the light source with the selected area of the eye fundus.

[0118] In some embodiments, the method further comprises setting or adjusting the position of the gaze fixation target based on whether the left or right eye of the user is being measured, wherein the adjustment required to the position of the gaze fixation target is determined based by the rotational position of the eyecup(s).P7521PC00

[0119] 18

[0120] In some embodiments, the method further comprises processing the optical spectrum / spectra to derive physiological information related to any one of the following: a concentration of total haemoglobin, a percentage of glycated haemoglobin, macular pigment concentration, foveal pigment concentration, oxygen saturation, the concentration of biomarkers or proteins.

[0121] In some embodiments, the method further comprises processing the optical spectrum / spectra to detect one or more physiological conditions, wherein the physiological conditions are selected from the group comprising: anaemia, diabetes mellitus, age-related macular degeneration, diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease, retinal vascular diseases and glaucoma.

[0122] In some embodiments, processing the optical spectrum / spectra is performed by the control unit.

[0123] In some embodiments, the method further comprises performing a readiness check prior to acquiring optical spectra, wherein the readiness check comprises using the light source or another light source to emit light, such as visible light or light that is invisible to the eye, into the eye of the user, using the light detector or another light detector to detect light reflected from the eye of the user, and analysing an intensity of the reflected light to determine whether conditions are not optimal for the acquisition of the optical spectrum, optionally, due to the eye being misaligned with the gaze fixation target prior to spectral acquisition, an eyelid is closed, the user is blinking, involuntary eye movements occurring, or that a pupil of the eye is too contracted. For example, the determination of whether the eye is misaligned with the gaze fixation target may be based on the intensity of the detected reflected light being within a range of intensity values that is characteristic of the tissue that comprises the fundus area that is being measured. Alternatively, the determination may involve comparing the detected light spectrum with a reference light spectrum to identify deviations indicative of misalignment, using a machine learning algorithm trained on a dataset of correctly aligned and misaligned eyes of users. Additionally, the readiness check may analyse temporal variations in the intensity of the reflected light to detect blinks or involuntary eye movements. For instance, a sudden drop followed by a rapid return to baseline intensity may indicate a blink.P7521PC00

[0124] 19

[0125] In some embodiments, based on the intensity of the determination performed by the readiness check, adjusting, using the control unit, the position of the gaze fixation target relative to the optical system may take place prior to acquiring an optical spectrum.

[0126] In some embodiments, the readiness determination is based on an intensity of reflected light being within a range of intensity values. When readiness is not achieved, the control unit can be programmed to automatically alter the position of the gaze fixation target, for example, by steps of less than 0.5 X mm, such as less than 0.25 X mm, such as less than 0.1 X mm (where X is the effective magnification factor of the optics), corresponding to 0.1 mm, 0.25 mm or 0.5 mm at the selected location in the eye. The readiness check can then be repeated until optimal conditions for acquiring a spectrum are reached. This iterative adjustment ensures that the device is optimally aligned with the eye for accurate spectral acquisition.

[0127] In some embodiments, an optical spectrum is obtained for both eyes of the user.

[0128] In some embodiments, the method comprises a step of normalising the acquired optical spectrum using light intensity measurements of the outgoing light emitted from the light source prior to its passage through the optical elements. These light intensity measurements are obtained using one or more detectors positioned to intercept a fraction of the emitted light without obstructing the primary optical path. The detectors are strategically placed to capture a sufficient portion of the emitted light to provide statistically reliable and representative intensity measurements. The normalised optical spectrum may then be compared to pre-stored reference values to assess data quality, ensuring that only accurate and reliable measurements are processed. For example, in some implementations, the method includes performing a quality assurance step by comparing the acquired optical spectrum to pre-stored reference values and determining whether the acquired optical spectrum meets a predefined quality assurance criterion. This step enhances the reliability of the data by filtering out measurements that do not meet the required standards.

[0129] Preferably, during the use of the handheld device for acquiring an optical spectrum or performing readiness checks, the eyecup remains stationary relative to the optical elements of the optical system. By maintaining the eyecup in a fixed position relative to the optical components, the method ensures that the alignment of the optical path isP7521PC00

[0130] 20

[0131] maintained throughout the acquisition stages of operations, minimising the potential for errors caused by shifts in the configuration of the device. This approach eliminates variability that might otherwise arise from unintended movement of the eyecup during operation, thereby improving the reproducibility and reliability of the spectral measurements.

[0132] In some embodiments, steps b) to f) are repeated if a portion of the returning light measured by the light detector comprises a saturated signal, and, optionally, wherein step d) is repeated with the light source emitting light at a lower intensity.

[0133] In some embodiments, a series of optical spectra are obtained, and wherein the method further comprises the step of excluding from an analysis one or more optical spectra from the series of optical spectra, such as, if an analysis determines that the eye was misaligned with the gaze fixation target during spectral acquisition, an eyelid was closed, the user was blinking, the presence of any involuntary eye movements, or that a pupil of the eye was too contracted.

[0134] Alternatively or additionally, one or more spectra that fail the quality assurance step, such as those deviating significantly from expected intensity thresholds or spectral patterns, may be rejected and replaced by new acquisitions to maintain data integrity. Another implementation may be that one or more spectra resulting from acquisitions intentionally added to induce eye accommodation are excluded from the analysis as these spectra are not intended to contribute to any diagnostic results. In cases where multiple spectra are acquired from the same location under identical conditions to enhance measurement accuracy through statistical averaging, any spectra identified as statistical outliers may also be excluded.

[0135] In some embodiments, optical spectrum acquisition is initiated by a voice command.

[0136] In some embodiments, performing the readiness check and acquiring an optical spectrum takes less than 200 milliseconds, such as less than 100 milliseconds, such as less than 50 milliseconds, such as less than 25 milliseconds.

[0137] Examples

[0138] Figure 1 illustrates an example of the handheld device 10, designed to measure optical spectra from a selected area of the retina 26 of a user’s eye. This figure specificallyP7521PC00

[0139] 21

[0140] depicts the optical and electronic components of the device but does not show the housing or eyecups, which are comprised in other embodiments and depicted in figure 2.

[0141] The optical system comprises optical elements such as a lens group 42, a lens group 47, a beam splitter 43, a reflective mirror 45, and a linear polariser 44. The optical elements image the digital screen 51 onto the retina of the user, focus light emitted from the light source 55 onto a desired area of the retina and direct light returning from the retina to the light detector. In the implementation shown in figure 1, the optical elements are arranged such that the light emitted by the light source and the light returning from the retina share a partially overlapping optical path. However, in other implementations, the optical paths may not be overlapping. It should be noted that the specific optical elements comprised within the optical system in this implementation are also not essential, and other combinations of optical components could be used to achieve the required focusing and manipulation of the optical beam to allow the device to be operable for measuring an optical spectrum / optical spectra from a selected area of the retina 26 of a user’s eye.

[0142] The light source 55 may, for example, include light sources and optics that produce a parallel beam or nearly parallel beam at wavelengths that facilitate spectra in a desired wavelength range, such as 400–850 nm. In some implementations, the light source may be based on laser diodes, LEDs, superluminescent diodes, ultrashort pulsed lasers, swept source lasers, very short external cavity lasers, vertical cavity surface emitting lasers, and supercontinuum lasers, or a combination of any of them. The control unit 80 may control various patterns of illumination, including pulse or continuous illumination, with configurable wavelengths, durations, and intensities. For example, the light source can produce a continuous beam of invisible light for performing a readiness check before emitting pulses of light within an adequate wavelength range (e.g., 420–620 nm) for the acquisition and recording of spectra. In other implementations, the light source can be configured to emit a Raman excitation laser beam at wavelengths such as 785 nm, with the spectrophotometer 60 adapted to measure and record corresponding Raman spectra. The same principles would be applicable to any wavelength used as the light source.P7521PC00

[0143] 22

[0144] Optionally, the light source 55 may include one or more detectors to measure the intensity of a portion of the emitted light. This measurement can serve to normalise the acquired spectra during subsequent data analysis, correcting for typical fluctuations in the emission intensity of the light source and enhancing the reliability of the device. The duration, intensity, and angular content of the light pulses produced by the light source may depend on the specific design of the optical system. For example, the intensity can be optimised to obtain a high signal-to-noise ratio (SNR) for spectral recordings while adhering to eye safety standards and regulations known to those skilled in the art. Furthermore, the light source 55 may include one or more detectors to measure the intensity of a portion of the emitted light. This measurement can, for instance, be used to normalise the acquired spectra during subsequent data analysis.

[0145] Beam 32 produced by the light source 55 can travel through lens group 47, linear polariser 44, reflective mirror 45, beam splitter 43, and lens group 42 before reaching the cornea 25, pupil 24, and eye lens 23 to illuminate a selected area of the retina 26, such as the optic nerve head 22. Through the arrangement of these optical components, the device may ensure that the diameter of the light beam remains within the pupil 24 of the user’s eye, even in cases where the pupil is fully contracted, and leaves most of its viewed area free of specular reflections. For example, the optical elements of the optical system may be configured to ensure that the diameter of the beam 32 is less than 1.1 mm, such as less than 0.9 mm, such as less than 0.7 mm, such as less than 0.5mm, such as less than 0.3 mm, along the section of the optical path that is located within the eyecup of the handheld device. This would allow the device to function without the need for the users to dilate their pupils using, for example, mydriatic drops for users whose diameter of pupil is larger than 1.5 mm, and will leave most of the viewed pupil area free of specular reflections of the illuminating light beam 32. The diameter of the beam at the portion of the retina being analyzed, such as the optic nerve head, preferably is small enough (e.g., less than 1 mm, such as less than 0.8 mm, such as less than 0.6 mm, such as less than 0.4 mm, such as less than 0.2 mm) to ensure it remains within the area of interest, even if the eye moves slightly between consecutive spectral acquisitions.

[0146] The control unit 80 is configured to adjust the position of the gaze fixation target on the digital screen 51 to ensure that the light beam 32 is focused on a desired retinal location, such as the optic nerve head 22 or the macula surrounding the fovea 21. TheP7521PC00

[0147] 23

[0148] gaze fixation target serves as a visual guide for aligning the user’s sight and ensuring optical alignment for spectral acquisition. During operation, inputs from the sensor 72 are analyzed by the control unit 80 to determine from which eye the user intends to acquire spectra and where on the screen 51 the gaze fixation target should be produced to bring the illumination spot generated by the light source 55 to the desired position in the eye.

[0149] In some implementations, the control unit may operate the device in one or more distinct modes to simplify operation and enhance accuracy. For example, the control unit may operate the system in an adjustment mode which automatically positions the gaze fixation target based on the user's selected eye and the rotational angle of the eyecups. The control unit may operate the device in a readiness check mode which activates the light source to emit a continuous invisible light beam, which is analyzed by the spectrophotometer 60 to ensure optimal alignment, eye openness, and readiness for spectral acquisition. Once conditions are deemed suitable, the device may transition into an acquisition mode in which it records spectra from the retina. The acquired spectra can then be processed locally or transmitted wirelessly for further analysis in a communication / analysis mode.

[0150] In some implementations, the light source 55 is configured to emit light at different wavelengths within the range of 400 to 850 nm and can produce visible light and / or light in other parts of the electromagnetic spectrum, such as near-infrared light.

[0151] In the optical system shown in figure 1, the light beam 32 passes through lens group 47, is reflected from the surface of reflective mirror 45, and is redirected by beam splitter 43 before traveling through lens group 42, cornea 25, pupil 24, and the eye lens 23 to illuminate a selected area of the retina 26, such as the optic nerve head 22. A portion of the light reflected from the retina forms the returning light 33, which passes back through the eye lens 23, pupil 24, cornea 25, lens group 42, beam splitter 43, and polariser 62 before reaching the spectrophotometer 60, which comprises the light detector. Lens group 42 is designed to image onto the plane of entrance slit 66 the pupil of an eye of average dimensions and average optical properties that is held at the average distance provided by eyepieces 102 or 104, when slightly pressed in. This design maximises the amount of light energy that reaches spectrophotometer 60 from the fundus of eye 20. While this design cannot fully compensate for differences amongP7521PC00

[0152] 24

[0153] individuals, such as variations in anterior chamber dimensions and cornea optical properties, it is based on average eye properties to ensure optical usability for a wide range of users.

[0154] Additionally, the design accounts for variability in facial structures, such as differences in eye depth and socket diameter. The eyecups are designed with an optimal balance of shape, structure, and material flexibility, allowing them to gently conform to a wide range of facial anatomies when lightly pressed. This configuration minimises variability in the distance between the eyes and the optical elements of the device, ensuring consistent alignment and proper optical positioning for the vast majority of users.

[0155] The diffuse nature of the reflection of light from the retina causes it to lose the linear polarisation imparted by polariser 44 to the irradiating light beam 32. Consequently, the returning light beam 33 is only partially attenuated by polariser 62. In contrast, specular reflections from the surface of the eye, which retain their linear polarisation, are significantly blocked by polariser 62 when appropriately aligned with respect to polariser 44. This configuration enhances the signal-to-noise ratio by minimising noise from specular reflections. However, the present disclosure is not limited to implementations of the handheld devices, such as the handheld device shown in figure 1, in which polarisers are present.

[0156] Preferably, as is implemented in the example shown in figure 1, the handheld device comprises a focusing knob 46, which allows the user to adjust the focus of the gaze fixation target for optimal sharpness. The knob 46 moves the board 50, which comprises the light source 55 and digital screen 51 to achieve the desired focus. Liners 48 and 49, which may be, for example, motorised supports, sliders, or guides, facilitate this adjustment. These advantageously provide stabilisation and smooth movement of the board during operation.

[0157] The coupling of the digital screen 51 and the light source 55 on the same movable board 50 ensures that when the user adjusts the focusing knob 46 to bring the gaze fixation target into focus, the light beam produced by the light source 55 is simultaneously brought into focus at the desired location. The optical system is specifically designed for a particular case, whether the fixation target and the light spot are intended to focus on the same plane (e.g., the retina, including the fovea for theP7521PC00

[0158] 25

[0159] fixation target and the optic nerve head for the light spot) or on different planes (e.g., the fixation target on the fovea and the light spot on Bruch’s membrane). In the latter case, the optical design of the light source ensures that the light beam is appropriately adjusted to achieve focus at the required depth.

[0160] The spectrophotometer 60 processes the returning light to measure the intensity of light, for example, as a function of wavelength. Optionally, as is the case for the handheld device shown in figure 1, the handheld device may comprise an annular aperture 64 and entrance slit 66 in front of the optical entrance to the spectrometer to further block specular reflections from the surface of the eye and optimise the signal-to-noise ratio during spectral acquisition.

[0161] The control panel 90 is also depicted and comprises a power switch 92, a spectrum acquisition activation button 98, and several indicator lamps 93, 94, 95, 97. The indicator lamps provide feedback on the operational state of the device, including battery status 93, readiness for acquisition 95, acquisition quality 97, and the need to repeat an acquisition 94. For instance, lamp 94 may indicate that one or more spectra in a measurement series contain portions of saturated signals. In such cases, the control unit may prepare the system for reacquisition of the entire programmed set of spectra under a uniformly reduced pulse intensity to avoid saturation while maintaining consistent illumination conditions across the series. Further, lamp 97 can indicate to the user that the acquired spectral data has met predetermined quality thresholds. In some implementations, the control panel 90 may only comprise the power switch 92 and the acquisition activation button 98.

[0162] The control panel may allow user interaction with the device, and the activation button 98 may be designed to be easily distinguishable by touch for convenient use without disturbing the alignment of the device during operation. The control unit may include electronics that supports voice recognition capabilities, enabling the user to trigger an acquisition with a voice command. This functionality can further enhance ease of use by allowing activation without physical interaction, minimising the risk of disrupting the device's positioning relative to the eyes.

[0163] The handheld device may wirelessly connect to an external device, such as a smartphone with an appropriate application installed. In this configuration, the voiceP7521PC00

[0164] 26

[0165] recognition capabilities of the smartphone could be utilised to process voice commands, enabling activation of the handheld device from the external device. This approach provides users with additional flexibility and convenience, particularly in situations where maintaining the device's alignment is critical for accurate measurements. Activation, such as, but not limited to, voice command, could also be initiated by a third party through the external device.

[0166] The power source 82 supplies power to the device and, in some implementations, is a rechargeable battery. This configuration supports portability and ease of use, allowing the device to be operated in various settings without requiring a direct power connection.

[0167] Figure 2 illustrates an external view of an embodiment of a handheld device 100. The internal components of the device, such as the optical and electronic systems, are enclosed within two primary housing sections: the optical housing 110, which contains the optical components, and the electronic housing 120, which contains the electronic components and, optionally, a power source.

[0168] The device comprises two eyecups, 102 and 104, positioned on opposite sides of the optical housing 110. These eyecups are designed to accommodate the user’s eyes and block external light, ensuring that ambient conditions do not interfere with the measurements. Advantageously, the eyecup corresponding to the non-measured eye ensures that the eye looking through it is in complete darkness, promoting spontaneous dilation of the pupil of both eyes. This facilitates improved alignment and measurement conditions for the optical system. The eyecups are mounted to rotate about a fixed reference axis 70, enabling the user to adjust the distance between the eyecups for optimal coverage of both eyes and a good view of the gaze fixation target with the examined eye. This adjustability ensures that the eyecups can comfortably fit a wide range of user anatomies.

[0169] The focusing knob 46 is visible on the side of the optical housing 110 and is used to adjust the focus of the gaze fixation target observed through the eyecups, as described in connection with the example shown in figure 1. By rotating the knob, the user can refine the focus for a clear and sharp visibility, allowing precise alignment of the optical system with the desired retinal location.P7521PC00

[0170] 27

[0171] A control panel 90 is located on the electronic housing 120 and provides an interface for operating the device. It may comprise features such as a spectrum acquisition activation button and indicator lamps, as described with reference to Figure 1, which provide feedback on the operational state of the device. The control panel is preferably positioned for easy access, ensuring the user can operate the device without disturbing its alignment. For example, in the embodiment shown, the control panel is on the side of the housing; however, in other embodiments, the control panel may be located anywhere on the housing that allows convenient user access.

[0172] Advantageously, as depicted in Figure 2, the electronic housing 120 may comprise a connector board 85, providing connectivity options such as charging and data transfer. The housing materials are selected to offer a secure grip while being easy to clean, ensuring durability and hygiene, especially when the device is used by multiple users.

[0173] Figure 3 illustrates the mechanism by which the handheld device 100 adjusts the position of the gaze fixation target on the digital screen 51, thus ensuring the light beam from the light source 55 is directed to the same portion of the retina regardless of adjustments made to fit the device to the user’s distance between the eyes or to switch between the left and right eye.

[0174] In the example shown in figure 3(a), the gaze fixation target 52 is positioned on the digital screen 51 such that the light beam produced by the light source 55 is directed to the optic nerve head 22 of the user’s right eye 20R. The positioning of the gaze fixation target ensures that the user’s line of sight aligns the optical system with the desired retinal location, thus allowing accurate spectral measurements. The gaze fixation target may be designed to have a specific shape and size to assist the user in achieving proper alignment. For instance, the gaze fixation target may take the form of a six-armed star, which is easily recognizable and allows the user to determine when the image is sharp. The size of the gaze fixation target should, preferably, be small enough to be fully visible within the user’s field of view without requiring eye movement but large enough to facilitate precise focusing. Its diameter may cover approximately 0.8 to 5 degrees of the user’s visual field, corresponding to about 0.24·X to 1.5·X mm on the digital screen, where X represents the optical magnification of the optical system.P7521PC00

[0175] 28

[0176] Figure 3(b) demonstrates how the device adjusts the gaze fixation target when the eyecups 102 and 104 are rotated about the reference axis 70 to reduce the distance between them. Such adjustments may be necessary to accommodate users with smaller distances between the eyes. The rotational angle α of the eyecups is detected by the sensor 72 and communicated to the control unit 80. Based on this input, the control unit recalculates the appropriate position for the gaze fixation target and adjusts its placement on the digital screen. In this example, the new gaze fixation target 54 is shown to maintain alignment with the optic nerve head 22, thus ensuring that the light beam remains focused on the same retinal location despite the change in positioning.

[0177] Figure 3(c) illustrates the adjustment required when switching from the right eye 20R to the left eye 20L. When switching eyes, the control unit calculates a new position for the gaze fixation target, as illustrated by fixation target 53 in figure 3(c). This adjustment ensures that the light beam is directed to the optic nerve head of the left eye while maintaining optical alignment with the desired area on the retina.

[0178] The ability of the system to automatically adjust the gaze fixation target based on the angular position of the eyecups and the selected eye enhances ease of use, enabling even non-clinically trained users, such as those operating the device at home, to obtain accurate and reliable measurements. This automatic functionality simplifies the operation of the device, eliminating the need for professional assistance and ensuring accessibility for a wide range of users.

[0179] Spectral analysis of acquired optical spectra

[0180] The spectra acquired from the eye of the user by the device disclosed in this invention can provide critical physiological information relevant to the diagnosis and monitoring of diseases with high prevalence. Advanced tools for the analysis of spectral data can extract valuable insights, enabling the identification of health parameters associated with various conditions.

[0181] These tools, which are well known to those skilled in the art, include principal components analysis (PCA), partial least squares (PLS), neural networks (NN), and other artificial intelligence (Al)-based methods (see, for example, 2023 Banerjee et al.). Typically, these analytical methods require a set of meta-data to adapt the tools, buildP7521PC00

[0182] 29

[0183] predictive models, or train them for extracting parameters of interest from the acquired spectral data.

[0184] For example, when using eye spectra obtained with the present invention to identify anaemia or assess the status of diabetes mellitus, meta-data would include, in the former case, the total haemoglobin concentration (CHb) in the blood, and in the latter case, the percentage of glycated haemoglobin (HbA1c). These blood parameters must be determined through standard, approved laboratory analysis of blood samples collected simultaneously with the spectral data from the eye.

[0185] The number of standard laboratory measurements required to develop an analysis program capable of predicting or estimating the parameters of interest from the acquired spectra depends on the analytical tool employed and the desired accuracy of the results. This requirement can range from dozens to tens of thousands of data points. Moreover, the analysis program can improve itself progressively as additional meta-data becomes available over time, enhancing its reliability and utility for clinical and non-clinical applications.

[0186] As an additional application of the invention disclosed herein, the system, including the device 10 and the control unit 80, can be programmed to acquire spectra from a grid of locations on the retina, for example, spaced 2 mm apart, around the center of vision (fovea). The resulting spectra may be utilised for various diagnostic and monitoring purposes, such as assessing the progressive degeneration of ganglion cells, which characterises glaucoma; identifying the accumulation of drusen and pigmentation changes associated with age-related macular degeneration (AMD); detecting microaneurysms, retinal haemorrhages, and vascular abnormalities linked to diabetic retinopathy (DR); monitoring changes in tissue oxygen saturation associated with glaucoma; and identifying biomarkers associated with certain neurological diseases, such as Parkinson's disease and Alzheimer's disease (see 2023 Lapointe et al. and references therein).

[0187] Furthermore, by collecting the acquired eye spectra and their corresponding meta-data into one or more databases, such as those managed through cloud-based applications, the invention enables continuous improvement in the accuracy of the calculated physiological values. This iterative process ensures that the results provided to theP7521PC00

[0188] 30

[0189] user immediately after acquiring the spectra from the eye become progressively more reliable and clinically relevant, enhancing the device's overall utility.

[0190] This example demonstrates how the concentration of haemoglobin (Hb) in the blood, denoted as CHU, and the percentage of glycated haemoglobin (HbA1c), denoted as %HbA1c, can be estimated through analytical calculations based on spectra acquired using the device disclosed herein. The parameter CHU is crucial for diagnosing anaemia, while %HbA1c is used to diagnose diabetes mellitus and to monitor how effectively the concentration of glucose in the blood of diabetic patients is maintained within recommended levels — an aspect highlighted in the background of this invention.

[0191] The calculations for CHU and %HbA1c are derived from two distinct spectra acquired using the device 10, as illustrated in Figure 1, and rely on the Beer-Lambert law, which has been demonstrated to be applicable to spectra obtained from the retina (see, for example, 2023 Akitegetse et al. and references therein). The two spectra differ in the volume of blood traversed by the light beam. This differentiation can be achieved by either moving the position of the gaze fixation target on screen 51, for instance, by 0.6 X mm, where X represents the optical magnification of the optical system in the device 10, or by capturing a sequence of images from the same retinal location at different stages of the cardiac cycle, as described in the detailed description of the invention.

[0192] According to the Beer-Lambert law, the reflectance R(A) of light from the retina can be expressed as:

[0193] Eq. 1 ) R(λ) = -ln(I / I0) = (ε(λ)+s(λ)) · L · c,

[0194] where ε(λ) represents the effective extinction coefficient, s(λ) denotes the scattering coefficient, L is the effective thickness of the tissue, and c is the concentration of the material having the extinction and scattering coefficients ε and s, respectively.

[0195] The retina, being a tissue rich in blood, also contains nerve cells and fibers.

[0196] Haemoglobin is the primary light-absorbing component within the retina. Consequently, the reflectance R(A) of the retina can be approximated by:P7521PC00

[0197] 31

[0198] Eq. 2) R(A) = £|-lb(A) ■ ClHb ' I— Bl + + SNonBI ' l-NonBI

[0199] =

[0200]

[0201] (£NonA1c(A) ' CNonA1c + £nbA1 c(A) ' CnbA1 c) ' 1—BI + S|\|onBI ’

[0202] Here,

[0203]

[0204] represents the scattering coefficient of blood, denotes the effective length of the blood column,

[0205]

[0206] is the scattering coefficient of non-blood tissue, and

[0207]

[0208] represents the effective length of the non-blood tissue.

[0209] The haemoglobin concentration, CHb, can be further divided into two components: the concentration of glycated haemoglobin (HbA1c) and the concentration of non-glycated haemoglobin:

[0210] Eq. 3) ClHb =CNonA1c+CHbA1c

[0211] Thus:

[0212] Eq. 4) £Hb(A)'CHb = £NonA1c(A) ' CNonA1c + £HbA1c(A) 'C|-lbA1c.

[0213] Here, £i-ib refers to the extinction coefficient of haemoglobin, while £NonAic and £HbAic denote the extinction coefficients of non-glycated haemoglobin and HbA1c, respectively (see Hendee and Westenskow, 1998, and Mandal and Manasreh, 2018).

[0214] We denote a spectrum acquired by the device 10, as shown in Figure 1, as l(A), where I represents the intensity and A represents the wavelength. This spectrum is illustrated by the beam 33. Similarly, the intensity of the light beam entering the eye, represented by the beam 32, is denoted as lo(A). As mentioned above, for the calculations, we use two spectra that we denote as la(A) and lb(A). These spectra are normalised by their respective source intensity values, measured by detectors in the light source 55. This normalisation allows us to treat lo(A) as equal for the acquisition of both spectra.

[0215] We define the difference in reflectance, 5Rab(A), between two states a and b (e.g. two adjacent locations on the retina or two different stages of the cardiac cycle) as:

[0216] Eq. 5) δRab(λ)=Ra(λ)–Rb(λ)=ln(lb / lo)–ln(la / lo)=ln(lb / la).P7521PC00

[0217] 32

[0218] This formulation eliminates the need to explicitly measure lo( ).

[0219] Substituting Equation (2) into this expression, we derive:

[0220] Eq. 6)

[0221] δRab(λ)=Ra(λ)–Rb(λ)=(εNonA1c(λ)·CNonA1c+εHbA1c(λ)·CHbA1c+SBl)·δLBl+SNonBl·δLNonBl.

[0222] Here:

[0223] 5l_BI=l-BI,a- l-BI,b>

[0224] represents the difference in the effective blood column length, and

[0225] 5l_NonBI=LNonBI,a- l-NonBI,b>

[0226] represents the difference in the effective non-blood tissue column length.

[0227] The values of£NonAic(A), CNOHAIC,£HbAic(A), CHbAic, SBI, and SNonBi are assumed to remain constant between states a and b, so that the difference in reflectance is attributed only to changes in LBI and LNOHBI.

[0228] However, the oxygen saturation of the blood may vary between states a and b. This variation could arise from differences in the relative volumes of arterial and venous blood in a and b. Additionally, the extinction coefficient£NonAic(A) of non-glycated haemoglobin differs for oxygenated and deoxygenated haemoglobin. As such,£NonAic(A) may not remain constant between the two states unless wavelengths corresponding to isosbestic points are selected.

[0229] The isosbestic points are defined as the wavelengths at which the extinction coefficients of oxygenated haemoglobin (£Hbo2(Ai)) and deoxygenated haemoglobin (EhbD( i)) are equal, i.e., εNonA1c(λi)≈εHbO2(λi)=εHbD(λi). Within the wavelength range ofP7521 PC00

[0230] 33

[0231] 350-600 nm, the isosbestic points occur at Ai = 390, 422, 452, 500, 529, 545, 570, 584 nm.

[0232] To isolate the values

[0233]

[0234] and getting rid of the dependence on

[0235]

[0236] (which we cannot measure directly), we define a ratio

[0237]

[0238] between 5Rab at two different isosbestic points Ai and A2of as:

[0239] Eq. 7) δRab(λ1) / δRab(λ2) = ln(lb(λ1) / la(λ1)) / ln( lb(λ2) / la(λ2)).

[0240] Substituting Equation (6) into this expression yields:

[0241] Eq. 8)

[0242] ((£NonA1 c(Al ) - CNonA1 c+£HbA1 c(Al ) - CHbA1 c+SBl) ' 61—BI + ' Sl-NonBl) I ((£NonA1 c(A2) ' CNonA1 c +£HbA1 c(A2) ' C|-lbA1 c+SBl) ' 61—BI + SNonBI ' Sl-NonBl)

[0243] = (£NonA1 c(Al ) - CNonA1 c+£HbA1 c(Al ) - CHbA1 c + ' (6 l—NonBl / 61— Bl) ) I

[0244]

[0245] + £HbA1 c(A2) ' C|-lbA1 c +

[0246] Here, it is assumed that the wavelength dependence of the scattering coefficients

[0247]

[0248] and SN0nBi is negligible.

[0249] Rewriting Equation (8), we obtain:

[0250] Eq. 9) 0 = CNonA1 c (£NonA1 c(Al )- Fl,2+ CHbA1 c (£HbA1 c(Al )- Fl,2' £|-lbA1 c(A2)) +

[0251]

[0252] (Sl-NonBl / bl-BI )) ■ (1

[0253] We note now that the extinction coefficients

[0254]

[0255] and £HbAic(A) can be measured in a laboratory setup and are considered here as known, and that F as defined in Eq. 7 is to be obtained by measurement with the device disclosed here. Thus, Eq. 9 can be considered to have three unknowns:

[0256]

[0257] CnbAi c, and

[0258]

[0259] In order to calculate these three unknowns, at least three equations are required. These can be obtained by extracting from the data acquired by the disclosed device F values at two additional pairs of wavelengths at isosbestic points, As and A4, and A5and Ae, and obtaining:

[0260] Eq. 10) 0 = CNonA1c·(εNonA1c(λ3)–F3,4·εNonA1c(λ4)) + CHbA1c·(εHbA1c(λ3)–F3,4·εHbA1c(λ4)) +

[0261]

[0262] ■ (1 -F^)P7521PC00

[0263] 34

[0264] and

[0265] Eq. 11) 0 = CNonA1c' (£NonA1 c(A5)-F5,6' £NonA1c(A6)) + CHbA1c' (£HbA1c(A5)-F5,6' £HbA1 c(A6)) +

[0266]

[0267] + SNonBI- (5l_NonBl / 6l-Bl)) ' (1 -Fs^)

[0268] Solving the equations set Eqs. 9-11, we obtain an estimate for the haemoglobin concentration in the blood of the user CHb by substituting the obtained values of

[0269]

[0270] and CHbAic into Eq. 3.

[0271] The percentage of glycated haemoglobin (HbA1c) in the blood of the user, denoted as %HbA1c, is defined by the equation:

[0272] %HbA1c = 100·CHbA1c / CHb.

[0273] Using the results derived from equations 9-11, %HbA1c can be further calculated as:

[0274] %HbA1C = 100 ' C

[0275]

[0276] HbAic / +CHbA1c)-

[0277] The calibration and normalisation of the device, as described in this disclosure, are well understood by those skilled in the art, as are the methods for applying the calculations to actual measurement results.

[0278] The analysis provided here serves to establish, using scientific principles, the applicability of the disclosed device. However, the practical implementation of advanced analytical techniques such as principal components analysis (PCA), partial least squares (PLS), neural networks (NN), and other machine learning tools will facilitate the actual calibration of the device. These tools, combined with accumulated measurement data over time, will enable continuous improvement in the accuracy and reliability of the device's performance.P7521PC00

[0279] 35

[0280] Further details of drawings

[0281] 10 — the handheld device

[0282] 20R — right eye of the user

[0283] 20L — left eye of the user

[0284] 21 — fovea of the eye

[0285] 22 — optic nerve head

[0286] 23 — eye lens

[0287] 24 — pupil of the eye

[0288] 25 — cornea of the eye

[0289] 26 — retina of the eye

[0290] 31 — light beam emitted from the screen

[0291] 32 — light beam emitted from the light source

[0292] 33 — light beam reflected from the inside of the eye fundus and passing through polariser

[0293] 42 — lens group

[0294] 43 — beam splitter for splitting light beams

[0295] 44 — linear polariser

[0296] 45 — reflective mirror

[0297] 46 — focusing knob

[0298] 47 — lens group

[0299] 48, 49 — liners

[0300] 50 — board

[0301] 51 — screen

[0302] 52, 53, 54 — gaze fixation targets

[0303] 55 — light source

[0304] 60 — spectrophotometer

[0305] 62 — linear polariser

[0306] 64 — annular aperture

[0307] 66 — entrance slit

[0308] 70 — rotational axis

[0309] 72 — sensor

[0310] 80 — control unit

[0311] 82 — power source

[0312] 85 — connector board(s)

[0313] 87 — charger interfaceP7521PC00

[0314] 36

[0315] 88, 89 — indicator lamps

[0316] 90 — user control panel

[0317] 92 — switch

[0318] 93, 94, 95, 97 — lamps

[0319] 98 — activation button

[0320] 100 — device

[0321] 102, 104 — eyecups

[0322] 110 — housing for optical components120 — housing for electronic componentsP7521PC00

[0323] 37

[0324] Items

[0325] 1. A handheld device for probing a selected area of the fundus of an eye of a user to obtain at least one parameter related to a physiological condition of the user, the handheld device comprising:

[0326] a housing integrated with:

[0327] an eyecup for the eye of the user,

[0328] an adjustment mechanism for adjusting a position and / or an orientation of the eyecup,

[0329] a sensor configured to output a signal indicative of the position and / or orientation of the eyecup,

[0330] a light source and a light detector,

[0331] a gaze fixation target,

[0332] an optical system comprising optical elements configured to:

[0333] image the gaze fixation target onto a retina of the user,

[0334] direct light emitted from the light source onto the selected area of the eye fundus of the user, and direct light returning from the eye fundus to the light detector; and

[0335] wherein the position of the gaze fixation target relative to the optical system is adjustable based on the signal to ensure that the selected area of the eye fundus is illuminated by light which is emitted from the light source and directed onto the eye fundus by the optical system.

[0336] 2. The handheld device according to item 1, wherein the handheld device further comprises a control unit which is configured to receive an input signal associated with the signal outputted by the sensor; and

[0337] wherein the control unit is configured to adjust the position of the gaze fixation target relative to the optical system based on the received input signal to ensure that the selected area of the eye fundus is illuminated by light which is emitted from the light source and directed onto the fundus of the eye by the optical system.

[0338] 3. The handheld device according to any preceding item, further comprising a screen configured to display the gaze fixation target.P7521PC00

[0339] 38

[0340] 4. The handheld device according to any preceding item, wherein the screen is an image display device, such as a digital display device, which displays the gaze fixation target, the control unit being configured to adjust the position of the gaze fixation target on the image display device by transmitting a control signal to the image display device.

[0341] 5. The handheld device according to any preceding item, wherein the screen is mechanically coupled to a motor which is configured to move the screen so as to adjust the position of the gaze fixation target.

[0342] 6. The handheld device according to any preceding item, wherein the optical system has a fixed optical magnification.

[0343] 7. The handheld device according to any preceding item, wherein the optical system has a tuneable optical magnification, and, optionally, wherein the optical magnification is controlled by the control unit.

[0344] 8. The handheld device according to any preceding item, wherein the handheld device comprises two eyecups.

[0345] 9. The handheld device according to any preceding item, wherein each eyecup is connected to a common pivot by a respective pivot arm, said pivot arm being rotatable about the pivot around a pivot axis.

[0346] 10. The handheld device according to any preceding item, wherein a distance separating a center of each eyecup and a point along the pivot axis which is located on a rotation plane formed by the pivot arms rotating about the pivot axis is greater than 21.5 mm, such as greater than 23 mm, such as greater than 25 mm, such as greater than 29 mm, such as greater than 31 mm, such as greater than 33 mm, such as greater than 35 mm, such as greater than 37 mm, such as greater than 39 mm, such as greater than 41 mm.

[0347] 11. The handheld device according to any preceding item, wherein the two pivot arms have a combined length of greater than 43 mm, such as greater than 46P7521PC00

[0348] 39

[0349] mm, such as greater than 50 mm, such as greater than 58 mm, such as greater than 62 mm, such as greater than 66 mm, such as greater than 70 mm, such as greater than 74 mm, such as greater than 78 mm, such as greater than 82 mm.

[0350] 12. The handheld device according to any preceding item, wherein the two pivot arms have a combined length such that the user has to rotate the two eyecups about the pivot to form an angle of less than 180 degrees between the two pivoting arms to accommodate a distance between the eyes of the user.

[0351] 13. The handheld device according to any preceding item, wherein the housing is divided into two bodies, the two bodies being pivotably connected along the pivot axis and each eyecup being arranged on in a respective body, an angle between the two bodies being adjustable so as to rotate the two eyecups about the pivot axis, and, optionally, the optical system is housed within one of the two bodies.

[0352] 14. The handheld device according to any preceding item, wherein the light emitted from the light source is prevented from entering one of the two eyecups, the other eyecup being accessible to light emitted by the light source and directed by the optical system so that the optical system is able to direct light into said other eyecup.

[0353] 15. The handheld device according to any preceding item, wherein the adjustment mechanism comprises the pivot, and, optionally, the two bodies of the housing, wherein the two bodies respectively form at least a part of each pivot arm.

[0354] 16. The handheld device according to any preceding item, wherein the rotation angle of the eyecups about the pivot axis is adjustable within a range of -43 degrees to 43 degrees, such as -42 degrees to 42 degrees, such as -40 degrees to 40 degrees, such as -38 degrees to 38 degrees, to accommodate a distance between the eyes of the user.

[0355] 17. The handheld device according to any preceding item, wherein the sensor is configured to output a signal indicative of an angle formed between the twoP7521PC00

[0356] 40

[0357] eyecups subtending about the pivot, and wherein the control unit is configured to determine whether a left eye or a right eye of the user is positioned in the eyecup configured to receive light emitted from the light source based on the angle, and wherein the control unit is configured to adjust the position of the gaze fixation target based on said determination.

[0358] 18. The handheld device according to any preceding item, wherein a rotation plane of the eyecups is divided into a first region corresponding to the user positioning their left eye in the eyecup configured to receive light emitted from the light source and a second region corresponding to the user positioning their right eye in the eyecup configured to receive light emitted from the light source, and wherein the control unit is configured to adjust the position of the gaze fixation target on the screen based on the eyecups being positioned within the first region or the second region.

[0359] 19. The handheld device according to any preceding item, wherein the control unit adjusts the position of the gaze fixation target by transmitting a command signal to the screen.

[0360] 20. The handheld device according to any preceding item, wherein the command signal transmitted by the control unit to the screen is determined at least partly based on a model of the optical path of light emitted by the light source through the optical elements of the optical system which is stored in a memory unit accessible to the control unit.

[0361] 21. The handheld device according to any preceding item, wherein the command transmitted by the control unit is further determined based on whether the left eye or the right eye of the user is positioned within the eyecup configured to receive light emitted from the light source.

[0362] 22. The handheld device according to any preceding item, wherein the optical system comprises one or more lenses configured to focus light emitted from the light source onto the selected area of the eye fundus of the user.

[0363] 23. The handheld device according to any preceding item, wherein the optical system comprises one or more beam splitters and / or one or more reflectiveP7521PC00

[0364] 41

[0365] mirrors for directing light emitted from the light source into the eye of the user and / or reflected light from the eye fundus of the user to the light detector.

[0366] 24. The handheld device according to any preceding item, wherein the optical elements are arranged such that light emitted by the light source and travelling towards the eye and light returning from the eye have a partially overlapping optical path.

[0367] 25. The handheld device according to any preceding item, wherein the light source is configured to emit light with a wavelength within the range of 400 nm to 850 nm.

[0368] 26. The handheld device according to any preceding item, wherein the light source is configured to emit visible light and / or near-infrared light.

[0369] 27. The handheld device according to any preceding item, wherein the light source is configured for emitting continuous light or pulses of light.

[0370] 28. The handheld device according to any preceding item, wherein the light source is operable at different wavelengths, such as at discrete wavelengths or across a continuous band of wavelengths.

[0371] 29. The handheld device according to any preceding item, further comprising one or more light detectors positioned to intercept a fraction of the emitted light.

[0372] 30. The handheld device according to any preceding item, wherein the light detector is configured to measure an intensity of light as a function of wavelength.

[0373] 31. The handheld device according to any preceding item, further comprising a spectrophotometer, which comprises the light detector.

[0374] 32. The handheld device according to any preceding item, wherein the control unit is further configured to adjust the position of the gaze fixation target to measure optical spectra from multiple locations on the retina.P7521PC00

[0375] 42

[0376] 33. The handheld device according to any preceding item, wherein the control unit is configured to derive physiological information from the optical spectra, and, optionally, the physiological information comprises haemoglobin concentration, glycated haemoglobin percentage, and oxygen saturation.

[0377] 34. The handheld device according to any preceding item, wherein the eyecup(s) is / are made of an opaque material to block external light and, optionally, wherein the eyecup(s) is / are adjustable to fit different user anatomies.

[0378] 35. The handheld device according to any preceding item, wherein the optical elements comprise one or more polarisers and / or one or more beam splitters.

[0379] 36. The handheld device according to any preceding item, wherein at least one optical element is configured to block specular reflections from the surface of the eye entering the light detector.

[0380] 37. The handheld device according to any preceding item, further comprising an aperture positioned between the eyecup(s) and the light detector which is configured to block specular reflections from the surface of the eye entering the light detector.

[0381] 38. The handheld device according to any preceding item, wherein the control unit is configured to adjust the position of the gaze fixation target on the screen to direct the light emitted from the light source onto an optic nerve head of the eye of the user, and optionally, the adjustment is based on a standard model of the eye stored in memory accessible to the control unit.

[0382] 39. The handheld device according to any preceding item, further comprising a focusing adjustment mechanism, such as a knob, allowing the user to optimise the focus of the gaze fixation target.

[0383] 40. The handheld device according to any preceding item, wherein the focusing adjustment mechanism is configured to adjust the position of the screen or one or more of the optical elements to allow the user to optimise the focus of the gaze fixation target.P7521PC00

[0384] 43

[0385] 41. The handheld device according to any preceding item, wherein upon rotation of the knob the position of the gaze fixation target is configured to move relative to the optical elements of the optical system.

[0386] 42. The handheld device according to any preceding item, wherein the optical system is configured to create a light spot in the eye fundus, the light spot being a focused region of illumination targeting the selected area of the fundus of the eye of the user for spectral analysis.

[0387] 43. The handheld device according to any preceding item, wherein the light spot has a diameter of less than 1 mm, such as less than 0.8 mm, such as less than 0.6 mm, such as less than 0.4 mm, such as less than 0.2 mm.

[0388] 44. The handheld device according to any preceding item, wherein the eyecups comprise a measurement eyecup and an inactive eyecup, the measurement eyecup being configured to receive light emitted from the light source, and the inactive eyecup being configured to not receive light emitted from the light source.

[0389] 45. A system comprising the handheld device according to any preceding item, the system further comprising:

[0390] a remote control unit in electronic communication with the handheld device and configured to perform one or more of the following:

[0391] (a) activate the device to perform spectral analysis, (b) receive data collected by the light detector and perform a spectral analysis of said collected data, and

[0392] (c) output feedback based on the spectral analysis which is indicative of a physiological condition of the user.

[0393] 46. The use of a handheld device according to any one of items 1 to 44 or a system according to item 45 to obtain an optical spectrum from a selected area of the fundus of an eye of a user.P7521PC00

[0394] 44

[0395] 47. The use of a handheld device according to item 46, wherein the optical spectrum is used for diagnosing one or more physiological conditions, wherein the physiological conditions are selected from the group comprising: anaemia, diabetes mellitus, age-related macular degeneration, diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease, retinal vascular diseases and glaucoma.

[0396] 48. The use of a handheld device according to item 46 for monitoring a percentage of glycated haemoglobin in the blood of a user.

[0397] 49. A method of acquiring an optical spectrum from a selected area of an eye fundus of a user, the method comprising:

[0398] a) providing a handheld device according to any one of items 1 to 44 or a system according to item 45,

[0399] b) arranging the eye of the user within the eyecup of the handheld device,

[0400] c) using the gaze fixation target to provide a visual aid to the user, the position of the gaze fixation target being configured to ensure that an optical path of the light emitted from the light source and passing through the optical elements of the optical system of the handheld device is directed onto the selected area of the eye fundus of the user,

[0401] d) using the light source to emit light and the optical system to direct the light onto the selected area of the eye fundus of the user, e) directing, using the optical system, light returning from the eye into the light detector,

[0402] f) measuring, using the light detector, the returning light to acquire an optical spectrum associated with the eye of the user.

[0403] 50. The method according to item 49, wherein the selected area is an optic nerve head in the eye.

[0404] 51. The method according to item 49 or item 50, the method further comprising the steps of:P7521PC00

[0405] 45

[0406] adjusting, using the adjustment mechanism, the position and / or orientation of the eyecup,

[0407] outputting, using the sensor, a signal indicative of the position and / or orientation of the eyecup,

[0408] transmitting the signal to the control unit, and

[0409] adjusting, using the control unit, the position of the gaze fixation target relative to the optical system based on the received signal.

[0410] 52. The method according to any one of items 49 to 51, further comprising repeating steps c) to f) so as to measure optical spectra from at least two different locations, such as at a grid of different locations within the selected area, wherein between measurements the position of the gaze fixation target is adjusted by the control unit to ensure that the light emitted by the light source is focused by the optical elements on a different location.

[0411] 53. The method according to item 49 or item 52, further comprising repeating steps c) to f) so as to measure optical spectra at different stages during the cardiac cycle.

[0412] 54. The method according to any one of items 49 to 53, further comprising adjusting the position and / or orientation of the eyecup(s) relative to the housing to accommodate the distance between the eyes of the user.

[0413] 55. The method according to any one of items 49 to 54, further comprising detecting a rotational position of the eyecup(s) about the pivot axis using the sensor, transmitting the detected position to the control unit, and setting or adjusting the position of the gaze fixation target to ensure optical alignment of the light emitted by the light source with the selected area of the retina of the eye.

[0414] 56. The method according to any one of items 49 to 55, further comprising setting or adjusting the position of the gaze fixation target based on whether the left or right eye of the user is being measured, wherein the adjustment required to the position of the gaze fixation target is determined based on the rotational position of the eyecup(s).P7521PC00

[0415] 46

[0416] 57. The method according to any one of items 49 to 56, further comprising processing the optical spectrum / spectra to derive physiological information related to any one of the following: a concentration of total haemoglobin, a percentage of glycated haemoglobin, macular pigment concentration, foveal pigment concentration, oxygen saturation, the concentration of biomarkers or proteins.

[0417] 58. The method according to any one of items 49 to 57, further comprising processing the optical spectrum / spectra to detect one or more physiological conditions, wherein the physiological conditions are selected from the group comprising: anaemia, diabetes mellitus, age-related macular degeneration, diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease, retinal vascular diseases and glaucoma.

[0418] 59. The method according to any one of items 49 to 58, wherein processing the optical spectrum / spectra is performed by the control unit.

[0419] 60. The method according to any one of items 49 to 59, further comprising performing a readiness check prior to acquiring an optical spectrum, wherein the readiness check comprises using the light source or another light source to emit light, such as visible light or light that is invisible to the eye, into the eye of the user, using the light detector or another light detector to detect light reflected from the eye of the user, and analysing an intensity of the reflected light to determine whether conditions are not optimal for the acquisition of the optical spectrum, optionally, due to the eye being misaligned with the gaze fixation target prior to spectral acquisition, an eyelid is closed, the user is blinking, involuntary eye movements occurring, or that a pupil of the eye is too contracted.

[0420] 61. The method according to item 60, wherein, based on the intensity of the determination performed by the readiness check, the position of the gaze fixation target is adjusted, using the control unit, relative to the optical system prior to acquiring an optical spectrum.P7521PC00

[0421] 47

[0422] 62. The method according to any one of items 49 to 61, wherein the readiness determination is based on an intensity of reflected light being below a threshold intensity value.

[0423] 63. The method according to any one of items 49 to 62, wherein an optical spectrum is obtained for both eyes of the user.

[0424] 64. The method according to any one of items 49 to 63, wherein steps b) to f) are repeated if a portion of the returning light measured by the light detector comprises a saturated signal, and, optionally, wherein step d) is repeated with the light source emitting light at a lower intensity.

[0425] 65. The method according to any one of items 49 to 64, wherein a series of optical spectra are obtained, and wherein the method further comprises the step of excluding from an analysis one or more optical spectra from the series of optical spectra, such as, if an analysis determines that the eye was misaligned with the gaze fixation target during spectral acquisition, an eyelid was closed, the user was blinking, the presence of any involuntary eye movements, or that a pupil of the eye was too contracted.

[0426] 66. The method according to any one of items 49 to 65, wherein optical spectrum acquisition is initiated by a voice command.

[0427] 67. The method according to any one of items 49 to 66, wherein performing the readiness check and acquiring an optical spectrum takes less than 200 milliseconds, such as less than 100 milliseconds, such as less than 50 milliseconds, such as less than 25 milliseconds.

Claims

P7521PC0048Claims1. A handheld device for probing a selected area of the fundus of an eye of a user to obtain at least one parameter related to a physiological condition of the user, the handheld device comprising:a housing integrated with:an eyecup for the eye of the user,an adjustment mechanism for adjusting a position and / or an orientation of the eyecup,a sensor configured to output a signal indicative of the position and / or orientation of the eyecup,a light source and a light detector,a gaze fixation target,an optical system comprising optical elements configured to:(i) image the gaze fixation target onto a retina of the user,(ii) direct light emitted from the light source onto the selected area of the eye fundus, and(iii) direct light returning from the eye fundus to the light detector; and wherein the position of the gaze fixation target relative to the optical system is adjustable based on the signal to ensure that the selected area of the eye fundus is illuminated by light emitted from the light source and directed onto the eye fundus by the optical system.

2. The handheld device according to claim 1, further comprising a control unit configured to receive an input signal associated with the signal outputted by the sensor, and to adjust the position of the gaze fixation target relative to the optical system based on the received input signal to ensure that the selected area of the eye fundus is illuminated by light emitted from the light source and directed onto the eye fundus by the optical system.

3. The handheld device according to any of the preceding claims, further comprising a screen configured to display the gaze fixation target,P7521PC0049wherein the screen is an image display device, such as a digital display device, the control unit being configured to adjust a position of the gaze fixation target on the image display device by transmitting a control signal to the image display device.

4. The handheld device according to any of the preceding claims, wherein the device comprises two eyecups, the two eyecups comprising a measurement eyecup and an inactive eyecup, the measurement eyecup being configured to receive light emitted from the light source and the inactive eyecup being configured to not receive light emitted from the light source.

5. The handheld device according to any one of claims 2 to 4,wherein the two eyecups are connected to a common pivot by respective pivot arms rotatable about a pivot axis,the sensor being configured to output a signal indicative of an angle formed between the two eyecups subtending about the pivot axis, andwherein the control unit is configured to determine whether a left eye or a right eye of the user is positioned in the eyecup configured to receive the light emitted from the light source based on the rotational angle,the control unit being configured to adjust a position of the gaze fixation target based on said rotational angle and eye determination so as to maintain alignment of illumination with a selected region of the eye fundus.

6. The handheld device according to claim 4 or 5, wherein the housing is divided into two bodies, the two bodies being pivotably connected along the pivot axis and each eyecup being arranged on a respective body, an angle between the two bodies being adjustable so as to rotate the two eyecups about the pivot axis.

7. The handheld device according to any one of claims 3 to 6, wherein the command signal transmitted by the control unit to the screen is determined at least partly based on a model of an optical path of light emitted from the light source through the optical elements of the optical system, the model being stored in a memory unit accessible to the control unit.P7521PC00508. The handheld device according to any preceding item, wherein the optical system is configured to create a light spot in the eye fundus, the light spot being a focused region of illumination targeting the selected area of the fundus of the eye of the user for spectral analysis.

9. The handheld device according to any one of the preceding claims, further comprising one or more light detectors positioned to intercept a fraction of the light emitted from the light source.

10. The handheld device according to any one of claims 2 to 9, wherein the control unit is further configured to adjust the position of the gaze fixation target to measure optical spectra from multiple locations on the retina.

11. The handheld device according to any one of claims 2 to 10, wherein the control unit is configured to derive physiological information from the optical spectra, and, optionally, the physiological information comprises haemoglobin concentration, glycated haemoglobin percentage, and oxygen saturation.

12. The handheld device according to any one of the preceding claims, wherein at least one optical element is configured to block specular reflections from the surface of the eye entering the light detector.

13. The handheld device according to any one of claims 3 to 12, wherein the control unit is configured to adjust the position of the gaze fixation target on the screen to direct the light emitted from the light source onto an optic nerve head of the eye of the user, the adjustment being based on a standard model of the eye stored in memory accessible to the control unit.

14. A method of acquiring an optical spectrum from a selected area of an eye fundus of a user, the method comprising:(a) providing a handheld device according to any one of claims 1 to 13; (b) arranging the eye of the user within the eyecup of the handheld device; (c) using the gaze fixation target to provide a visual aid to the user, the position of the gaze fixation target being configured to ensure that an optical path of light emitted from the light source and passing through the opticalP7521PC0051elements of the optical system of the handheld device is directed and focused onto the selected area of the eye fundus of the user;(d) using the light source to emit light and the optical system to direct the light onto the selected area of the eye fundus of the user;(e) directing, using the optical system, light returning from the eye into the light detector; and(f) measuring, using the light detector, the returning light to acquire an optical spectrum associated with the eye of the user.

15. The method according to claim 14, wherein the selected area is an optic nerve head in the eye.

16. The method according to any one of claims 14 to 15, further comprising repeating steps (c) to (f) so as to measure optical spectra from at least two different locations, such as at a grid of different locations within the selected area, wherein between measurements the position of the gaze fixation target is adjusted by the control unit to ensure that the light emitted by the light source is focused by the optical elements on a different location.

17. The method according to any one of claims 14 to 16, further comprising repeating steps (c) to (f) so as to measure optical spectra at different stages during the cardiac cycle.

18. The method according to any one of claims 14 to 17, further comprising processing the optical spectrum / spectra to derive physiological information related to any one of the following: a concentration of total haemoglobin, a percentage of glycated haemoglobin, macular pigment concentration, foveal pigment concentration, oxygen saturation, or the concentration of biomarkers or proteins.

19. The method according to any one of claims 14 to 18, further comprising processing the optical spectrum / spectra to detect one or more physiological conditions, wherein the physiological conditions are selected from the group comprising: anaemia, diabetes mellitus, age-related macular degeneration,P7521PC0052diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease, retinal vascular diseases, and glaucoma.

20. The method according to any one of claims 14 to 19, further comprising performing a readiness check prior to acquiring an optical spectrum, the readiness check comprising:(i) using the light source or another light source to emit light, such as visible light or light that is invisible to the eye, into the eye of the user;(ii) using the light detector or another light detector to detect light reflected from the eye of the user; and(iii) analysing an intensity of the reflected light to determine whether conditions are not optimal for the acquisition of the optical spectrum.

21. The method according to claim 20, wherein, based on the intensity determination performed by the readiness check, the position of the gaze fixation target is adjusted, using the control unit, relative to the optical system prior to acquiring an optical spectrum.

22. The method according to any one of claims 14 to 21, wherein the readiness determination is based on an intensity of reflected light being below a threshold intensity value.

23. The method according to any one of claims 14 to 22, wherein steps (b) to (f) or steps (c) to (f) are repeated if a portion of the returning light measured by the light detector comprises a saturated signal, and, optionally, wherein step (d) is repeated with the light source emitting light at a lower intensity.

24. The method according to any one of claims 14 to 23, wherein a series of optical spectra are obtained, and wherein the method further comprises the step of excluding from an analysis one or more optical spectra from the series of optical spectra, such as, if an analysis determines that the eye was misaligned with the gaze fixation target during spectral acquisition, an eyelid was closed, the user was blinking, the presence of any involuntary eye movements, or that a pupil of the eye was too contracted.P7521PC005325. The method according to any one of claims 14 to 24, wherein performing the readiness check and acquiring an optical spectrum takes less than 200 milliseconds, such as less than 100 milliseconds, such as less than 50 milliseconds, such as less than 25 milliseconds.

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