Device, system and method to detect physiological eye characteristic(s) and, or eye position of eye through closed eyelid(s)

Abstract

A device to detect a proxy of pupil size, pupil size, a pupillary light reflex, or an eye position includes substrate, a first plurality of light emitters, a second plurality of light emitters, and a plurality of light sensors, which are small enough in number and distributed across the substrate such that the device can overlie a closed eyelid and conform to a curvature of the eye. A system can monitor and, or diagnose a patient or subject based on detected proxy of pupil size, pupil size, pupillary light reflex, or eye position. The system can employ machine-learning or an artificial neural network and generate alerts and notifications.

Description

DEVICE, SYSTEM AND METHOD TO DETECT PHYSIOLOGICAL EYE CHARACTERISTIC(S) AND, OR EYE POSITION OF EYE THROUGH CLOSED EYELID(S)CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This patent application claims priority of U.S. Patent Application No.63 / 744,948, filed on January 14, 2025, and U.S. Patent Application No. 63 / 820,249, filed on June 9, 2025, and U.S. Patent Application No. 63 / 841,701, filed on July 10, 2025, the entire disclosures of which are hereby incorporated by reference herein for all purposes.BACKGROUNDField

[0002] The present disclosure generally relates to devices, systems and methods to automate detection at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid. The physiological eye characteristic(s) can, for instance be a pupil size, pupillary light reflex (e.g., duration of pupillary dilation and fixation) or a physiological eye characteristic that correlates to pupil size and, or pupillary light reflex and hence is a proxy for pupil size. The present disclosure generally relates to devices, systems and methods to assess health or wellness conditions of humans based at least in part on at least one of detected physiological eye characteristic(s) (e.g., a proxy for pupil size, pupil size, detected pupillary light reflex) and, or detected eye position detected through a closed eyelid, and for instance employing trained artificial neural networks and / or machine-learning.

[0003] The human eye includes an iris. The iris comprises circular and radial muscles and is the anterior portion of the uvea. The iris is generally annular with a generally central opening in that constitutes the pupil. The pupil is actually located slightly nasal and inferior to the iris center. The average diameter of the iris is 12 mm, and its thickness varies. It is thickest in the region of the collarette, a circular ridge approximately 1.5 mm from the pupillary margin.’ The collarette divides the iris into the pupillary zone, which encircles the pupil, and the ciliary zone, which extends from the collarette to the iris root. The iris changes the size of the pupil to control the amount of light that passes to photoreceptors of the retina. The diameter of the pupil can vary from 1 mm to 10mm depending on lighting conditions. A fully dilated pupil is typically in the range of 6 mmto 10 mm, inclusive, in diameter, while a constricted pupil is in the range of 1 mm to 4 mm, inclusive, in diameter.

[0004] Control of the pupils involves various neurological pathways. Thus, medical personnel (e.g., doctors, surgeons, nurses, anesthesiologists, emergency medical technicians, paramedics) will often evaluate pupil size and / or pupillary light reflex response in assessing a medical condition of a patient. Evaluation of pupil size and / or pupillary light reflex response can provide an indication of the health, wellness or medical condition of a patient. Such may be useful in assessing critically injured or critically ill patients. Evaluation of pupil size and / or pupillary light reflex response is often employed in diagnosing and / or assessing traumatic brain injury (TBI). Abnormalities in pupillary responses and / or pupil size asymmetry (anisocoria) may be indicative of underlying neurological issues. For example, pupillary changes may be indicative of brainstem oxygenation and perfusion or ischemia. Evaluation can include not only considering the pupil size and / or pupillary light reflex response of one eye or the other eye, but can include comparing the pupil size and / or pupillary light reflex response of one eye to the pupil size and / or pupillary light reflex response of the other eye. Fixed and dilated pupils are typically indicative of a condition requiring urgent medical attention.

[0005] Consideration of pupillary behavior is often employed with unconscious patients, whether sedated, passed out, asleep or comatose.

[0006] Pupil evaluations are typically conducted manually, by visual observation. When the patient is unconscious, the eyelids of the patient are manually manipulated into an open configuration, and pupil size and pupillary light reflex (also referred to as pupillary reactivity) are visually determined, often with the aid of a light (e.g., penlight). Several parameters can be measured such as baseline size, latency, rate of constriction, maximal rate of constriction, minimal size, percent change, rate of dilation. These characteristics can be compared over time, compared between eyes and compared with population norms. Alterations in any of these parameters are often indicative of an underlying medical issue.

[0007] Manual pupillary evaluation is typically performed periodically, and thus is likely to miss a change in condition or detect a change several hours after the change occurs. Measurement of both eyes at the same time is difficult, and some parameters used to assess medical conditions involve comparing the response and state of each eye. Such is also a laborious task, requiring skilled personnel. Such evaluation can also be inaccurate, for instance due inconsistencies between individuals performing the manualevaluation or even inconsistencies in performance by a given individual over time.Manual manipulation can also lead to eye injury, for instance scratching to tearing the cornea as the eyelid is forced open.

[0008] At least one group has proposed detecting pupil size and pupillary light reflex with a closed eyelid. The group generally describes projecting white light toward the eye to cause a pupillary response and then projecting infrared light through a rear or side of the head toward vitreous of the eye, the infrared light which would then presumably pass through the pupil and be detected by an IR camera positioned in front of the head. See, e.g, US11,122,972 and US11,684,255.

[0009] There is a need for improved devices, systems and methods detect at least one of pupil size, pupillary light reflex or eye position through a closed eyelid.BRIEF SUMMARY

[0010] The present disclosure generally relates to devices, systems and methods to detect at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid.

[0011] The devices, systems and methods to detect at least one of physiological eye character! stic(s) and, or eye position through a closed eyelid include a substrate, a first plurality of light emitters carried by the substrate and electrically coupled to the one or more circuit traces, the light emitters of the first plurality of light emitters operable to emit light in a first range of wavelengths (e.g., 400nm-700nm, or 520nm-650nm, or 600nm) to stimulate a light reflex of the iris of the eye, for example regardless of the direction of gaze, a second plurality of light emitters carried by the substrate and electrically coupled to the one or more circuit traces, the light emitters of the second plurality of light emitters operable to emit light in a second range of wavelengths (e.g., 800nm-2500nm), and a plurality of light sensors carried by the substrate and electrically coupled to the one or more circuit traces. The substrate, light emitters and light sensors are all positioned in front of the eye(s) to project light through the closed eyelid(s) and to detect light returned (e.g., reflected, refracted) from the iris through the closed eyelid(s).

[0012] The substrate can comprise at least one electrically insulative layer and one or more circuit traces. The substrate is preferably conformable to a portion of the eye when it is positioned over or on an outer surface or even secured or adhered to the outer surface of the closed eyelid(s). The substrate comprises a central region and a peripheral region, the central region which overlies the iris and the pupil of the eye when the device ispositioned over or on or even secured or adhered to the closed eyelid(s) and the peripheral region spaced radially outward of the central region. The light emitters of the first plurality of light emitters are oriented to transmit light toward the pupil, for example regardless of the direction of gaze, when the substrate is positioned over or on or even secured or adhered to the closed eyelid(s). The light emitters of the second plurality of light emitters positioned in the peripheral region of the substrate spaced radially outward from the central region of the substrate and oriented to transmit light a shallow angle where a respective principal axis of emission of each of the light emitters of the second plurality of light emitters does not intersect the vitreous of the eye when the substrate over or on or even secured or adhered to the closed eyelid(s). In at least some implementations, a respective principal axis of emission and the respective principal axis of emission is tangential to the vitreous of the eye when the substrate is positioned over or on the outer surface of the at least one closed eyelid.

[0013] In some implementations, the light emitters of the first plurality of light emitters are distributed across two or more regions positioned of the substrate and oriented to transmit light toward the pupil when the substrate is positioned over or on or even secured or adhered to the closed eyelid(s) without regard to the direction of gaze, which may be different for different patients, the principle axis of emission could intersect part of the vitreous. In other implementations, the light emitters of the first plurality of light emitters are positioned in the central region of the substrate and oriented to transmit light toward the pupil when the substrate is positioned over or on or even secured or adhered to the closed eyelid(s).

[0014] Light emitters and light sensors are typically rigid and not pliable. The approach described herein positions the light emitters of the second plurality of light emitters positioned in the peripheral region of the substrate, dispersing the light emitters over a larger areas of the substrate as compared to other approaches which might position all of the light emitters to be directly in front of the pupil or the iris, advantageously increasing the flexibility and hence conformability of the device.

[0015] The light sensors of the second plurality of light sensors positioned across the substrate and oriented to receive light returned from the iris through the closed eyelid(s) when the substrate is positioned over or on or even secured or adhered to the closed eyelid(s). In some implementations, the light sensors of the second plurality of light sensors are positioned across the substrate, for instance in both a central region and a peripheral region of the substrate. In some implementations, the light sensors of thesecond plurality of light sensors are positioned in the central region of the substrate but not in the peripheral region of the substrate, which may aid in conformability or pliability of the device.

[0016] In some implementations, the devices, systems and methods to detect at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid include one or more devices that are secured or adhered to or otherwise lay on the outer surface of one or both closed eyelids.

[0017] In some implementations, the devices, systems and methods to detect at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid include a device that is sized to cover one eyelid of one eye of a pair of closed eyes. The device can be secured (e.g., adhesive, bio-compatible adhesive, bio-compatible pressure sensitive adhesive) to one eyelid of a pair of closed eyelids of one eye. The device (e.g, in the form of a patch) can transmit light through the one eyelid of a pair of closed eyelids of one eye. The device receives light that passes through the one closed eyelid of the one eye of the pair of closed eyes. Alternatively, the device (e.g, in the form of a mask or in the form of two patches) can transmit light through the eyelids of a pair of closed eyelids of both eyes. The device receives light that passes through the closed eyelids of the pair of closed eyes. Where two patches are employed for a single subject, at least one of the patches can communicate with the other one or the patches, the patches can communicate with one another, or the patches each communicate with a processor-based device (e.g., smartphone, tablet computer) that is physically distinct from the patches. Communicates can employ wireless communications including radios, receivers, transmitters and antennas, light-based communications for instance LED-receiver pairs, or even wired communications. The use of a mask or two patches can advantageously allow the physiological eye characteristic(s) and, or eye position of both of the eyes to be compared to one another for consistency, which aids in assessing medical condition or rendering a diagnosis. Additionally or alternatively use of a mask can advantageously allow the physiological eye characteristic(s) and, or eye position of both of the eyes to be compared to one another for consistency, where differences in an otherwise healthy subject (e.g., during a sleep study) may indicate that the mask has shifted on the face of the subject and the data being collected may no longer be reliable.

[0018] In some implementations, the devices, systems and methods to detect at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid include a device that is sized to cover both eyelids of a pair of closed eyelids of one eye.The device can be secured (e.g., adhesive, bio-compatible adhesive, bio-compatible pressure sensitive adhesive) to both eyelids of a pair of closed eyelids of one eye. The device can transmit light through both eyelids of a pair of closed eyelids of one eye. The device receives light that passes through both eyelids of a pair of closed eyelids of one eye.

[0019] In some implementations, the devices, systems and methods to detect at least one of physiological eye characteristic(s) and, or eye position through a closed eyelid include a mask (e.g., eye mask) worn over one or both eyes, and one or more devices are located in the mask to overlay respective outer surfaces of the closed eyelids.

[0020] In at least one implementation, a method includes: detecting the eye position of the eye; and selectively controlling which of the light emitters of the first plurality of light emitters is active based at least in part on the eye position of the eye to steer the light emitted by the light emitters of the first plurality of light emitters. Since it is not known a priori which way an eye will be pointing, the device can detect and, or track eye position. Steering includes selectively activating light sources at different locations on the substrate so that a direction of the illumination from the substrate is steered or otherwise controlled. The device can then steer the emission of the light emitters of the first plurality of light emitters (e.g., white light source) in real-time based on eye position and a feedback loop. This can advantageously allow a location of the light emitters of the first plurality of light emitters to be spread out more diffusely on the substrate. For example, the light emitters of the first plurality of light emitters are dispersed across the central region and the peripheral region of the substrate. Such advantageously provides for increased pliability and, or compliance and, or conformability of the substrate.

[0021] In at least one implementation, a method of operation includes comparing a determined amount of infrared light (aka infra-red light) returned to one or more threshold values. Notably, in this implementation, the device employs the amount of infrared light in lieu of determining a size of the pupil. The amount of infrared light returned from the eye is a proxy for pupil size that provides technical advantages over directly determining pupil size, as described herein. The threshold values can correlate to various pupil sizes, and, or to various medical conditions. The use of amount of returned infrared light advantageously avoids computationally complicated and costly image processing, speeding up operation and allowing use of less complicated, smaller and, or more efficient processors as compared to what is used for conventional image processing (e.g., GPUs in addition to CPUs) and, or as compared to determining the pupil size itself.

[0022] In at least one implementation, a method of operation includes comparing which light sensors detected infrared light returned (e.g., relative positions and / or spacing) to threshold value(s) to one or more threshold values. Notably, in this implementation, the device employs the knowledge of which light sensors detected infrared light in lieu of determining a size of the pupil. The threshold values can correlate to various pupil sizes, and, or to various medical conditions. The use of the identify, position or relative spacing of light sensors that detect returned infrared light advantageously avoids computationally complicated and costly image processing, speeding up operation and allowing use of less complicated, smaller and, or more efficient processors as compared to what is used for conventional image processing (e.g., GPUs in addition to CPUs) and, or as compared to determining the pupil size itself.

[0023] In at least one implementation, a method includes: directing diffuse illumination toward the eye from the light emitters of the first plurality of light emitters to activate the retina, for example via an extra-pupillary pathway. Diffuse illumination can be emitted by the light emitters of the first plurality of light emitters, or the light emitted by the light emitters of the first plurality of light emitters may be diffused via an optical component (e.g., optical diffuser) positioned along an optical path that extends from the light emitters of the first plurality of light emitters.

[0024] The approach described herein eliminates the need to manually manipulate the eyelid(s) of a patient, reducing potential harm to the patient, reducing the need for a skilled medical professional, and allowing continuous or near continuous evaluation of at least one of physiological eye characteristic(s) (e.g., proxy for pupil size, pupil size, pupillary light reflex), and, or eye position through a closed eyelid. Such can also essentially eliminate the subjectivity and inconsistencies in evaluation. The more conformable substrate can also advantageously increase patient comfort. The approach described herein does not transmit light toward the vitreous cavity of the eye, and does not detect light exiting the pupil of the eye. Rather, light is directed from in front of the eye toward the iris, and light returned (e.g., reflected, refracted) from the iris is detected. This is a more direct approach employed by others, without the need to produce infrared light at sufficient energy levels to pass through the head, into the vitreous and out the pupil. Instead, the margin of the iris can be evaluated or measured based on the return of light from the iris.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

[0025] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

[0026] In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not necessarily drawn to scale, and some of these elements may be arbitrarily enlarged and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn, are not necessarily intended to convey any information regarding the actual shape of the particular elements, and may have been solely selected for ease of recognition in the drawings. In the drawings, identical structures, elements or parts that appear in more than one drawing are generally labeled with a same numeral in all the drawings in which they appear. Alternatively, elements or parts that appear in more than one drawing may be labeled with different numerals in the different drawings in which they appear.

[0027] Figure 1 A is a schematic diagram of a device to detect at least one of a physiological eye characteristic(s), and, or an eye position of an eye having an iris and a pupil through a closed eyelid, the device including a substrate, a first plurality of light emitters, a second plurality of light emitters, and a plurality of light sensors, according to at least one illustrated implementation.

[0028] Figure IB is a schematic diagram of the device of Figure IB illustrating one or more circuit traces of the substrate, according to at least one illustrated implementation.

[0029] Figure 1C is a schematic diagram of the device Figure 1 A with an iris and pupil of an eye overlaid on the substrate to illustrate an exemplary positioning of the first plurality of light emitters, the second plurality of light emitters and the light sensors relative to the iris and pupil when the device is located on an outer surface of a closed eyelid, according to at least one illustrated implementation.

[0030] Figure ID is a schematic diagram of a device to detect at least one of a physiological eye characteristic(s), and, or an eye position of an eye having an iris and a pupil through a closed eyelid, the device including a substrate, a first plurality of light emitters, a second plurality of light emitters, and a plurality of light sensors in a symmetrical layout, according to at least another illustrated implementation.

[0031] Figure IE is a schematic diagram of a device to detect at least one of a physiological eye characteristic(s), and, or an eye position of an eye having an iris and apupil through a closed eyelid, the device including a substrate, a first plurality of light emitters, a second plurality of light emitters, and a plurality of light sensors in an asymmetrical layout, according to at least a further illustrated implementation.

[0032] Figure 2A is a schematic diagram that maps various components ( / .< ., first plurality of light emitters, second plurality of light emitters, light sensors) of the device of Figure 1 A into respective functional regions of the device, according to at least one illustrated implementation.

[0033] Figure 2B is a schematic diagram showing an exemplary iris and pupil overlying the functional regions of the device illustrated in Figure 2A, according to at least one illustrated implementation.

[0034] Figure 3 A is a cross-sectional view of a device to detect at least one of a physiological eye, and, or an eye position of an eye having an iris and a pupil through a closed eyelid, the device including a substrate, light emitters in the form of light emitting diodes, and light sensors in the form of photodetectors, according to at least one illustrated implementation.

[0035] Figure 3B is a cross-sectional view of the device of Figure 3 A with an adhesive layer overlying a first face and an opaque exterior overlying a second face, the second face opposed from the first face across a thickness of the substrate, according to at least one illustrated implementation.

[0036] Figure 3C is a representative view of the device of Figure 3B applied to a closed eyelid and overlying a cornea of the eye, according to at least one illustrated implementation.

[0037] Figure 3D is a representative view of the device of Figure 3C applied to a closed eyelid and overlying a cornea of the eye, illustrating how the substrate conforms to a curvature of a portion of the eye, according to at least one illustrated implementation.

[0038] Figure 3E shows a cross-section of the optical light path, showing the shallow angle emission of the LEDs, which allows for scattering off of the iris.

[0039] Figure 3F shows an eye, closed upper eyelid and lower eyelid with the device positioned in front of the eye and over an exterior or outer surface of the closed upper and lower eyelids, better illustrating the conformance to the curvature of the relevant portions of the eye (e.g., cornea and portion of closed eyelids overlying the cornea), with a ray trace of light emitted by light emitters and detected by light detector, according to at least one illustrated implementation.

[0040] Figure 3G is a schematic diagram of a simplified geometrical model of an eye and some representative angles, according to at least one illustrated implementation.

[0041] Figures 4A, 4B, 4C, 4D, 4E, and 4F are cross-sectional views sequentially illustrating a manufacturing process to manufacture a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0042] Figure 5A is an isometric view of a patch employing a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0043] Figure 5B is an isometric view of a mask employing one or more devices such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0044] Figure 5C is an isometric view of a subject wearing a mask employing one or more devices such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, and a processorbased device where a communications system of the mask is wirelessly communicatively coupled to the processor-based device, wherein the mask is illustrated as used as part of a sleep study, according to at least one illustrated implementation.

[0045] Figure 5D is an isometric view of a subject wearing a mask employing one or more devices such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, and a medical provider employing a user interface that is part of the mask in assessing and, or treating the subject, wherein the mask illustrated as used a combat environment, according to at least one illustrated implementation.

[0046] Figure 5E is an isometric view of a subject wearing a mask employing one or more devices such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, and processorbased device, a communications system of the mask wiredly communicatively coupled to the processor-based device, wherein the mask is illustrated as used in an intensive care or operating room environment, according to at least one illustrated implementation.

[0047] Figure 6A is a block diagram showing a system to detect at least one of physiological eye characteristic(s) and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3 A-3D, according to at least one illustrated implementation.

[0048] Figure 6B is a block diagram showing a system to detect at least one of physiological eye characteristic(s) and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3 A-3D, according to at least another illustrated implementation.

[0049] Figure 6C is a block diagram showing a system to detect at least one of physiological eye characteristic(s) and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3 A-3D, according to at least yet another illustrated implementation.

[0050] Figure 7 is a block diagram of a processor-based system according to at least one illustrated implementation, the processor-based system useful with the devices and systems of the present disclosure.

[0051] Figure 8 is a flow diagram of a high-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0052] Figure 9 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0053] Figure 10 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0054] Figure 11 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0055] Figure 12 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0056] Figure 13 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0057] Figure 14 is a flow diagram of a low-level method of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0058] Figure 15A is a heat map of a spatial irradiance in an area for a centered (0X= 0°, 9y= 0°) pupil with a 7 mm pupil diameter, according to at least one illustratedimplementation.

[0059] Figure 15B is a heat map of the spatial irradiance in the area for a centered (0X= 0°, 9y= 0°) pupil with a 3 mm pupil diameter, according to at least one illustrated implementation.

[0060] Figure 15C is a graph of corresponding measured irradiance in six photodetectors for a centered (0X= 0°, 9y= 0°) pupil for different pupil diameters, according to at least one illustrated implementation.

[0061] Figure 15D is a heat map of a spatial irradiance in an area for an oblique gaze direction (rotation angles 9X= 7°, 9y= 7°) with a 7 mm pupil diameter, according to at least one illustrated implementation.

[0062] Figure 15E is a heat map of a spatial irradiance in an area for an oblique gaze direction (rotation angles 9X= 7°, 9y= 7°) with a 3 mm pupil diameter, according to at least one illustrated implementation.

[0063] Figure 15F is a graph of corresponding measured irradiance in six photodetectors for an oblique gaze (9x = 7°, 9y = 7°) for different pupil diameters, according to at least one illustrated implementation to a centered eye (9x = 0°, 9y = 0°), according to at least one illustrated implementation.

[0064] Figure 16 is a schematic diagram of an exemplary device, according to at least one illustrated implementation.

[0065] Figure 17A is a graph showing cornea safety calculations for NIR light with a maximum exposure time for single pulse of 940 nm IR LED at different distances from the cornea, according to at least one illustrated implementation.

[0066] Figure 17B is a graph showing a maximum duty cycle for continuous IR light at different distances from the cornea, according to at least one illustrated implementation.

[0067] Figure 17C is a graph showing retina safety calculations for visible light, according to at least one illustrated implementation.

[0068] Figure 17D is a graph showing a radiance at the retina for different visible wavelengths with an LED radiant intensity of 5 mW / sr and the continuous exposure safety limit given by LB(X) = 100 / B(l) W / (m2*sr) where B(l) is the blue hazard function, according to at least one illustrated implementation.

[0069] Figure 18 is a graph showing retina safety calculations safety limit for continuous exposure at the retina ( / .< ., red line or upper-most line in graph), radiance at the retina for continuous light exposure at an intensity of 5 mW / sr) ( / .< ., blue line or intermediate line in graph), shows radiance at the retina for pulsed light with a 6.67%duty cycle at an intensity of 5 mW / sr ( / .< ., gray line or lower-most line in graph) is below (within) the safety limit, according to at least one illustrated implementation.DETAILED DESCRIPTIONPreamble

[0070] In the following description, certain specific details are set forth in order to provide a thorough understanding of various disclosed implementations. However, one skilled in the relevant art will recognize that implementations may be practiced without one or more of these specific details, or with other methods, components, materials, etc. In other instances, well-known structures associated with computer systems (for example digital computer systems, superconducting computers, quantum computer systems, and server computers), and / or communications networks have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the implementations.

[0071] Unless the context requires otherwise, throughout the specification and claims that follow, the word “comprising” is synonymous with “including”, and is inclusive or open-ended (i.e., does not exclude additional, unrecited elements or method acts).

[0072] Reference throughout this specification to “one implementation” or “an implementation” means that a particular feature, structure or characteristic described in connection with the implementation is included in at least one implementation. Thus, the appearances of the phrases “in one implementation” or “in an implementation” in various places throughout this specification are not necessarily all referring to the same implementation. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more implementations.

[0073] As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the context clearly dictates otherwise.

[0074] As used herein and in the claims, terms “patient” and “subject” refer to any human individual which are subject to determination of at least one of: a physiological eye character! stic(s) (e.g., proxy for pupil size, pupil size, pupillary light reflex response) and, or eye position. The patient or subject may be a subject of head trauma, or undergoing brain surgery, or may have an ischemic or hemorrhagic stroke, or may be undergoing other surgery for an unrelated condition.

[0075] As used herein, the terms “physiological eye characteristic” or “physiological eye characteristics” refer to pupil size, pupillary light reflex (e.g., duration of pupillary dilation and fixation) and including physiological eye characteristics which represents those pupil size values or pupillary light reflex values or from which those values can be derived or inferred based on a correlation, for instance inferred from an amount of light returned from the eye through the closed eyelid. For instance, the amount of light returned from an eye through closed eyelid with be a function the amount of dilation of the pupils.

[0076] As used herein, the term “pupillary light reflex” includes, but are not limited to one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline.Pupillary light reflex can include a first derivative of pupil size (change in size over time) or even a second derivate of pupil size (how quickly the rate of change changes over time). Pupillary light reflex can also refer to a comparison between the response of the two eyes of the patient.

[0077] As used herein and in the claims the terms “pupil size” and “pupil diameter” may be used interchangeably and refer to a size / diameter of an outer perimeter of the opening of the iris of the eye or a size / diameter of an inner perimeter of the iris itself, which controls an amount of light that passes through to a retina. In some implementations, the pupil size is determined in response to light illuminating on the eye, to provoke the pupillary light reflex, and hence the determination is characterized herein as the pupillary light reflex response. Pupil size typically refers to a distance measured across a pupil between two diametrically opposed points at inner edges of iris. Some implementations advantageously employ proxies for pupil size, simplifying computational complexity as well as simplifying circuitry, and thereby allowing faster operation, a smaller device, with less heat dissipation and other benefits.

[0078] As used herein, the term “reference”, with regards to physiological eye characteristic, proxy for pupil size, pupil size and, or pupillary reflex, and, or eye position, refers to a determined reference physiological eye characteristic, proxy for pupil size, pupil size and, or a determined reference speed of pupil size change, and, or a determined reference eye position, respectively, such as, but not limited, to medically established normal physiological eye characteristic, proxy for pupil size, pupil size and, or normal pupillary reflex, and, or normal eye position, or determined reference physiological eye characteristic, proxy for pupil size, pupil size medically associated with specific neurological conditions, determined reference pupillary light reflex responsemedically associated with specific neurological conditions, and, or determined reference eye position medically associated with specific neurological conditions. Additionally, or alternatively, the reference physiological eye characteristic, proxy for pupil size, pupil size and, or reference pupillary light reflex response, and, or reference eye position, may be a patient specific. Such can take into consideration that physiological eye characteristics, proxy for pupil size, pupil sizes and / or pupillary reflex are known to vary between individuals and typically vary based on age.

[0079] As used herein, the terms “light sensor” and “light sensors” refer to structures that detect or measure light in one or more portions of the electromagnetic spectrum (e.g., infrared light), and can include various types of photosensors for instance photodetectors, photodiodes, phototransistors, APDs, PMTs, photoconductors, CCD / CMOS sensors, various cameras (e.g., digital cameras).

[0080] The terms “approximately” and “about” may refer to + / — 0.5%, + / -1%, + / -2%, + / -5%, or+ / -10%.

[0081] The term “shallow” with respect to angle means an angle at which a principal axis of emission or optical axis does not intersect the vitreous of the eye, whether or not the principal axis of emission or optical axis actually intersect another portion of the eye.

[0082] The headings and Abstract of the Disclosure provided herein are for convenience only and do not interpret the scope or meaning of the implementations.

[0083] Figures 1A, IB and 1C show a device 100 to detect at least one of physiological character! stic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye, according to at least one illustrated implementation.

[0084] The device includes a substrate 102, a first plurality of light sources or light emitters 104, a second plurality of light sources or light emitters 106, and a plurality of light sensors 108 carried by the substrate 102.

[0085] The substrate 102 can take the form of a flexible circuit board or flexible printed circuit board (PCB). The substrate 102 can include one or more electrically insulative layers, one or more electrically conductive or wiring layers which can take the form of patterned electrically conductive layers to provide one or more electrically conductive traces 110 (also known as circuit traces). The electrically conductive traces 110 can be carried on an outer surface 102a of the substrate 102, an inner surface of the substrate 102 or both, and may also include one or more vias to electrically couple electrically conductive traces one different surfaces or layers of the substrate 102. In some implementations, the substrate 102 can include one or more strain relief features, forexample slots or holes 107 formed in or through the substrate 102. The slots or holes 107 can be formed extending inward from an outer periphery or edge of the substrate 102, and, or can be formed spaced away from the outer periphery or edge of the substrate 102, to increase pliability. While illustrated as a single substrate 102, some implementations can employ two, three or more separate and distinct substrates (e.g., first flexible printed circuit board, second flexible printed circuit board) for example to limit or even prevent light leakage and, or increase conformity to the eye and closed eyelid. Thus, for example, the first plurality of light emitters 104 and, or the second plurality of light emitters 106 can be carried by a first substrate 102 while the light sensors 108 can be carried by a second substrate 102, the first and the second substrates 102 physically coupled (e.g., packaged) together to form the device 100. Whether one, two or more substrates 102, the substrate(s) 102 can have one or more strain relief structures (e.g., cutouts, openings, notches, serpentine edges) to increase or enhance pliancy and, or conformability to a curvature of the eyelid and underlying eye.

[0086] The first plurality of light sources or light emitters 104, the second plurality of light sources or light emitters 106, and, or the plurality of light sensors 108 can be carried by (e.g., mounted on, mounted in, adhered to, or otherwise supported directly or indirectly) the substrate 102. The first plurality of light sources or light emitters 104, the second plurality of light sources or light emitters 106, and, or the plurality of light sensors 108 can be electrically coupled to the respective ones of electrically conductive traces 110, for example via solder.

[0087] The first plurality of light sources or light emitters 104 are operable to emit light in a in a first range of wavelengths and at a first intensity level sufficient to stimulate a reflex of the iris of the eye (z.e., pupillary light reflex). The first plurality of light sources or light emitters 104 can, for example, take the form of light emitting diodes (LEDs) of any of a variety of types of LEDs. Unpackaged LEDs and in particular micro-light emitting diodes (micro-LEDs) may be particularly advantageous. Such can, for example, allow a spacing between the LEDs and the eyelid to be reduced, allow the LEDs to be placed closer to one another other, and allow for thinner LEDs, which LEDs may even themselves be flexible, advantageously reducing a radius of curvature and, or increasing the pliability and, or compliance and, or conformability of the substrate with the LEDs mounted. Such can release or omit the substrate that typically carries the LED. Such can result in less waveguiding of light emitted by the LEDs (e.g., micro-LEDs). Such can reduce dispersion of light emitted by the LEDs, advantageously improving spatialresolution and increasing directionality. Various embodiments can advantageously employ a relatively small number light sources or light emitters 104 (e.g., less than 30, less than 20, less than 10), which is significantly reduces stiffness of the substrate 102, allowing the substrate 102 to be more pliable and hence conformable to the curvature of the closed eyelid, particular the portion of the eyelid overlying the cornea. Such can also reduce power consumption and heat dissipation. Various embodiments can advantageously employ one or more lenses (e.g., micro-lenses) aligned with the optical axes (e.g., principal axes of emission) of light sources or light emitters 104 and, or the light sources or light emitters 106. Various embodiments can advantageously employ one or more lenses (e.g., micro-lenses) aligned with the optical axes of the plurality of light sensors 108. Micro-lenses over the LEDs can focus and, or direct the light to advantageously increase the SNR.

[0088] The second plurality of light sources or light emitters 106 operable to emit light in a second range of wavelengths to transit through a closed eyelid and return through the closed eyelid in order to detect physical characteristics of the iris or margins thereof from light returned (e.g., reflected, refracted) from the iris through the closed eyelid. The second plurality of light sources or light emitters 106 can, for example, take the form of light emitting diodes (LEDs) of any of a variety of types of LEDs.

[0089] The second range of wavelengths different from the first range of wavelengths. For example, the first range of wavelengths includes wavelengths between 400 nm inclusive and 700 nm inclusive (e.g., visible spectrum). The first range of wavelengths can, for example, include wavelengths between 520 nm and 650 nm, inclusive. The first range of wavelengths can, for example, include wavelengths corresponding to the color blue. The second range of wavelengths includes wavelengths between 800 nm inclusive and 2500 nm inclusive, and thus can take the form of infrared light which has a relatively high permeability through the tissue of the eyelid.

[0090] The second plurality of light emitters can be selected or operated to emit light in the near infrared (IR) range, l=about 800 nm to about 2500 nm or higher wavelengths. The second plurality of light emitters can be selected or operated to emit light within the range of 800 nm to 2500 nm, inclusive, and preferably in the short-wave infrared (SWIR) range of about 900 nm to 2500 nm, inclusive, 950 nm to 2200 nm, inclusive, 950 nm to 2500 nm, inclusive, or other suitable ranges. In general, longer wavelengths may be preferred so long as suitable sensors (e.g., light sensors, photodetectors) responsive to those wavelengths are available and employed. The light emitted by the second pluralityof light emitters can be selected or operated has wavelength and / or intensity selected so as to not affect the size of the pupils. For example, it may be advantageous to avoid wavelengths near 1450 nm since those wavelengths tend to be highly absorbable by water.

[0091] The plurality of light sensors 108 are responsive or sensitive to wavelength of light returned from the iris, for example wavelengths in the second range of wavelengths (e.g., infrared or near infrared or (SWIR)). The plurality of light sensors 108 can take the form of photodetectors. Various embodiments can advantageously employ a relatively small number of light sensors 108 (e.g., less than 30, less than 20), which is significantly less than the number of individual sensors in a typical digital camera chip. This significantly reduces stiffness of the substrate 102, allowing the substrate 102 to be more pliable and hence conformable to the curvature of the closed eyelid, particularly the portion of the eyelid overlying the cornea. The plurality of light sensors 108 can, for example, take the form of charge-coupled devices (CCDs), complementary metal oxide semiconductor (CMOS) devices, silicon (Si) photodetectors, quantum dot-based detectors, non-junction detectors (e.g., bolometers, pyroelectric materials, resonators). For example, the plurality of light sensors 108 can employ any one or more of: Si, GaAs, InGaAs, InGaAs, InGaAs, InGaAs, InAs, InSb, InAsSb, InAsSb, HgCdTe, Ge, PbS, and, or PbSe based sensors. It can also be advantageous to assess values of a sensor on a pixel-by-pixel basis.

[0092] The device 100 can optionally contain one or more optics. For example, one or more flat optics can be mounted or carried by the substrate 102, aligned with or along the optical axis of the light sources or light emitters 104, 106 and, or the light sensors 108. The optics can include a patterned or etched surface or surfaces. The optics advantageously allow control of the angle of the emission of the light sources or light emitters 104, 106 and, or the angle of the light returned to and detected by the light sensors 108. The optics can shape the light that the light sources emit and, or shape the light to be received by the light sensors. The optics can tighten an optical cone of the emitted and, or returned light. The optics can additionally or alternatively provide spectral control over emitted and, or returned light.

[0093] With particular reference to Figure 1C, a human eye 112 includes an iris 114 and a pupil 116. The iris 114 contracts and expands, thereby controlling a size (e.g., outer diameter) of the pupil 116, and thereby controlling the amount of light that passes to the retina (not illustrated) of the eye.

[0094] The second plurality of light sources or light emitters 106 (e.g., infrared LEDs, SWIR LEDs), which are primarily used to map the iris location and size, are positioned on the substrate 102 so as to be placed around an outer perimeter or margin 114a of the iris 114 when the device 100 is placed over or on the outer surface of the eyelid (not illustrated in Figure 1C). The first plurality of light sources or light emitters 104 (e.g., shorter wavelength LEDs), which are primarily used to stimulate the optical photoresponse, are positioned on the substrate 102 so as to be placed closer to a center of the pupil 116 when the device 100 is placed over or on the outer surface of the eyelid. The plurality of light sensors 108 (e.g., photodetectors) are positioned on the substrate 102 so as to be placed over the pupil 116, over the iris 114 and even in some instances radially outwardly of the expected outer perimeter or margin of the iris 114 when the device 100 is placed over or on the outer surface of the eyelid, thereby permitting the detection of light scattered from second plurality of light sources or light emitters 106 independent of the eye position. In some implementations, the light sensors 108 are positioned or distributed across the substrate 102, for instance in both a central region and a peripheral region of the substrate 102. In some implementations, the light sensors 108 are positioned in the central region of the substrate 102 but not in the peripheral region of the substrate 102, which may aid in conformability or pliability of the device.

[0095] Figure ID shows a device lOOd to detect at least one of a physiological eye character! stic(s) , and, or an eye position of an eye having an iris and a pupil through a closed eyelid employing a symmetrical layout of components, according to at least another illustrated implementation.

[0096] The device lOOd is similar or even identical in many respects to the device 100 (Figures 1 A-1C). Similar or even identical structures are represented using the same reference numbers and the description of such is not repeated out of the interest of brevity. Only some of the significant differences between the device lOOd and the device 100 are discussed below.

[0097] In contrast to the device 100 (Figures 1 A-1C) the device lOOd (Figure ID) has a different total number of a first plurality of light emitters 104 (e.g., nine, illustrated as circles), a different total number of a second plurality of light emitters 106 (e.g., eight, illustrated as hexagons), and a different total number of a plurality of light sensors 108 (e.g., six, illustrated as boxes), as well as a different layout of the first plurality of light emitters 104, the second plurality of light emitters 106, and the plurality of light sensors 108.

[0098] The light emitters of the second plurality of light emitters 106 are angularly arrayed about a central axis and the light sensors of the plurality of light sensors 108 are angularly arrayed about the central axis. For example, the light emitters of the second plurality of light emitters 106 can be angularly spaced equally from one another about the central axis and the light sensors of the plurality of light sensors 108 can be angularly spaced equally from one another about the central axis. The light emitters of the second plurality of light emitters 106 are spaced at a first distance from the central axis and the light sensors of the plurality of light sensors 108 are spaced at a second distance from the central axis. The first distance from the central axis can be between approximately 8mm and approximately 10mm, inclusive, and preferably approximately 9mm, where approximately means plus or minus 10%. The second distance from the central axis can be between approximately 4mm and approximately 6mm, inclusive, and preferably approximately 5mm, where approximately means plus or minus 10%. The second plurality of light emitters 106 can include eight light emitters, arrayed at approximately 45° from one another about the central axis, where approximately means plus or minus 10%. It is noted that the first plurality light emitters 104 (e.g., visible light emitting LEDs) does not affect pupil imaging resolution and thus can be placed in various locations on a substrate 102 relative to the second plurality of light emitters 106 and the plurality of light sensors 108, although at least one emitter should be located relatively centrally and some light emitters located peripheral in all directions of vision. Even given the lack of effect on pupil imaging resolution, it can still be advantageous to optimize the layout of the first plurality light emitters 104 for conformability of the substrate 102 and, or device 100, lOOd, lOOe to a curvature of the eye.

[0099] The light emitters of the first plurality of light emitters 104 can include a first set of three or more light emitters that are angularly arrayed about the central axis. The light emitters 104 of the first set of three or more light emitters of the first plurality of light emitters 104 can be angularly spaced equally from one another about the central axis. The light emitters of the first set of three or more light emitters of the first plurality of light emitters 104 can advantageously be angular arrayed midway between each light emitter of a corresponding closest pair of light emitters of the second plurality of light emitters 106 to maximize a distance from the light emitters of the corresponding closest pair of light emitters of the second plurality of light emitters 106. The light emitters of the first plurality of light emitters 104 can include a second set of one or more light emitters that spaced radially inward of the first set of three or more light emitters of the first pluralityof light emitters 104. The second set of one or more light emitters can include a single light emitter that is coaxial with the central axis. The first set of three or more light emitters of the first plurality of light emitters 104 can be spaced at a third distance from the central axis. The third distance from the central axis is between approximately 6mm and approximately 8mm, inclusive, and preferably approximately 7mm, where approximately means plus or minus 10%. The light emitters of the first plurality of light emitters 104 can be spaced radially inward from the light emitters of the second plurality of light emitters 106.

[0100] The device lOOd can advantageously measure pupil size from 1.5 m to 8 mm diameter, inclusive, at a higher resolution (e.g., ,0.1 mm) than the device 100. The device lOOd can advantageously measure eye rotations for approximately plus or minus 50°, with a high resolution (e.g., 2° with error of approximately 0.5 °). The device lOOd advantageously achieves a minimum light sensor 108 (e.g., photodetector) spacing of 1 mm apart for enhanced flexibility relative to the device 100.

[0101] Modeling of device lOOd was performed using the following assumptions: eyelid thickness: 0.6mm-1.6mm; eyelid transmission: 20%-50%; iris reflectance: 10%-50% with most simulations performed at 20%; sclera reflectance: 50%; and scattering defined by the Henyey-Greenstein relationship.

[0102] Figure IE shows a device lOOe to detect at least one of a physiological eye characteristic(s), and, or an eye position of an eye having an iris and a pupil through a closed eyelid employing an asymmetrical layout, according to at least another illustrated implementation.

[0103] It is noted that each light emitter (e.g., LED)-light sensor (e.g., photodetector) pair has a region of maximum spatial sensitivity. Computational optimization (e.g., machine learning to estimate errors) can advantageously be used to assist in the determination of optimized positions for the light emitters and light sensor to maximize coverage of the region of interest. Given the lack of effect on pupil imaging resolution, machine learning can be used to optimize a layout of the second plurality of light emitters 106 and the plurality of light sensors 108 for pupil resolution without concern for the layout of the first plurality of light emitters 104. Yet it can still be advantageous for a human to optimize the layout of the first plurality light emitters 104 for conformability (e.g., a pliability) of the substrate 102 and, or device 100, lOOd, lOOe to a curvature of the eye, for instance accounting for the size of the various components and, or a stiffness ofthe substrate 102 with the various components secured thereto in various possible positions.

[0104] The device lOOe is similar or even identical in many respects to the device 100 (Figures 1 A-1C). Similar or even identical structures are represented using the same reference numbers and the description of such is not repeated out of the interest of brevity. Only some of the significant differences between the device lOOe and the device 100 are discussed below.

[0105] In contrast to the device 100 (Figures 1 A-1C) the device lOOe (Figure IE) is optimized for spatial resolution of light emitter / light sensor pairs and thus has a different total number of a first plurality of light emitters 104 (e.g., seven, illustrated as circles), a different total number of a second plurality of light emitters 106 (e.g., twelve, illustrated as hexagons), and a different total number of a plurality of light sensors 108 (e.g., eight, illustrated as squares), as well as a different layout of the first plurality of light emitters 104, the second plurality of light emitters 106, and the plurality of light sensors 108.

[0106] The light emitters of the second plurality of light emitters 106 are angularly arrayed about a central axis and the light sensors of the plurality of light sensors are angularly arrayed about the central axis. The light emitters of the second plurality of light emitters 106 can, for example, be angularly spaced unequally from one another about the central axis and the light sensors of the plurality of light sensors can, for example, be angularly spaced unequally from one another about the central axis. The first plurality of light sensors can, for example, be spaced radially inward of the light emitters of the second plurality of light emitters. The first plurality of light sensors can, for example, include eight light sensors, located as respective locations. The light sensors of the first plurality of light sensors can, for example, be angular arrayed at approximately 32 degrees, 90 degrees, 148 degrees, 204 degrees, 236 degrees, 270 degrees, 304 degrees, and 336 degrees, about the central axis, successively counterclockwise starting from an X axis of an XY plan to which the central axis is perpendicular, where approximately means plus or minus 10%. The light sensors of the first plurality of light sensors can, for example, be spaced from the central axis by approximately 5.545mm, 3.387mm, 5.545mm, 6.41mm, 5.737mm, 4.727mm, 5.737mm, and 6.41mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

[0107] The second plurality of light emitters can, for example, include twelve light emitters, located at respective locations. The light emitters of the second plurality of light emitters can, for example, be spaced approximately at 2 degrees, 23 degrees, 55 degrees, 90 degrees, 125 degrees, 157 degrees, 178 degrees, 199 degrees, 233 degrees, 270 degrees, 307 degrees, and 341 degrees, about the central axis, successively counterclockwise starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%. The light emitters of the second plurality of light emitters can, for example, be spaced from the central axis by approximately distances, 8.324mm, 7.502mm, 6.853mm, 5.904mm, 6.853mm, 7.502mm, 8.324mm, 8.895mm, 7.777mm, 9.129mm, 7.777mm, and 8.895mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

[0108] The first plurality of light emitters can, for example, include seven light emitters, located at respective locations. The light emitters of the first plurality of light emitters can, for example, be spaced approximately at 0 degrees, 90 degrees, 180 degrees, 236 degrees, 249 degrees, 291 degrees, and 304 degrees, about the central axis, successively counterclockwise starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%. The light emitters of the first plurality of light emitters can, for example, be spaced from the central axis by approximately distances, 4.000mm, 1.000mm, 4.000mm, 3.606mm, 8.544mm, 8.544mm, and 3.606mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.PD Positions

[0109] Notably, the device lOOe is has an asymmetry, with more light sensors 108 (e.g., photosensors for instance photo detectors) on a lower portion (e.g., lower half) of the device lOOe or substrate 102 than on an upper portion (e.g., upper half) of the device lOOe or substrate 102, which advantageously accounts for fact that the extreme gaze direction with the eyes looking up is different than the extreme gaze direction with the eyes looking down (i.e., human eyes are able to look farther downward than upward). The device lOOe can advantageously improve pupil diameter estimation by about ten times relative toinitial designs (e.g., Figure 1A). The device lOOe advantageously has a region-of-interest optimized for: gaze plus 20° down, and plus or minus 300left and right. The device lOOe advantageously achieves a minimum light sensor 108 (e.g., photodetector) spacing for enhanced flexibility relative to the device 100.

[0110] Figure 2A maps various components (i.e., first plurality of light emitters, second plurality of light emitters, light sensors) positioned on the substrate 102 of the device 100 of Figure 1A into respective functional regions of the device 100 or substrate 102.[OHl] In particular, the device 100 or substrate 102 includes a reactive or stimulus light illumination region 200. The device 100 or substrate 102 includes a detection region 202 (e.g., photodetection region) that overlaps the reactive or stimulus light illumination region 200 and extends radially outward from the reactive or stimulus light illumination region 200. The device 100 or substrate 102 includes an IR region 204 that extends radially outward from the detection region 202.

[0112] Figure 2B shows an exemplary iris 114 and pupil 116 overlying functional regions of the device 100 as illustrated in Figure 2A.

[0113] In particular, the reactive or stimulus light illumination region 200 (e.g., shorter wavelength LEDs used to stimulate the optical photo-response) is positioned on the substrate 102 so as to overlie at least a portion of the pupil 116 when the device 100 is placed over or on the outer surface of the eyelid. The IR region 204 (e.g., IR LEDs which are primarily used to map the iris location and size) is positioned on the substrate 102 so as to overlie and encompass the iris (e.g., placed to be spaced radially outward of an outer perimeter or margin 114a of the iris 114) when the device 100 is placed over or on the outer surface of the eyelid are placed. The detection region 202 area (e.g., photodetectors via which photodetection occurs) is positioned on the substrate 102 so as to encompass a portion of the pupil 116 and at least a portion of the iris (e.g., placed to be radially proximate an outer perimeter or margin 114a of the iris 114) when the device 100 is placed over or on the outer surface of the eyelid are placed.

[0114] Figure 3A shows a device 300a to detect at least one of physiological eye character! stic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye having an iris and a pupil through a closed eyelid, according to at least one illustrated implementation. The device 300a can be the same as, or similar to, the device 100 previously illustrated and described.

[0115] The device 300a includes a substrate 302. The substrate 302 carries a plurality of light emitters (e.g., first plurality of light sources or light emitters 104, second plurality oflight sources or light emitters 106), illustrated as light emitting diodes (LEDs) 304. The substrate 302 carries a plurality of light sensors (plurality of light sensors 108), illustrated as light sensor 306.

[0116] The substrate 302 can comprise or take the form of an electrically insulative substrate or layer illustrated as a polyimide substrate or layer 308. The substrate 302 can comprise or take the form of an electrically conductive substrate or layer, carried by the electrically insulative substrate or layer, which can be patterned to form one or more circuit traces and illustrated as patterned copper foil layer 310. The substrate 302 can comprise an electrically conductive coupling substrate or layer, carried by the electrically conductive substrate or layer, is illustrated as a solder mask layer 312. The solder mask layer 312 physically and electrically couples the LEDs 304 and light sensors 306 to the circuit traces formed by the patterned copper foil layer 310.

[0117] Figure 3B shows a device 300b to detect at least one of pupillary characteristic(s), and, or an eye position of an eye having an iris and a pupil through a closed eyelid, according to at least one illustrated implementation.

[0118] The device 300b is similar to the device 300a (Figure 3 A), although also includes laminated films on an exterior facing surface 302a and on a skin facing surface 302b of the substrate 302. An opaque layer film 314 can be laminated or otherwise secured on the exterior facing surface 302a. The opaque layer film 314 can advantageously reduce a leakage of light into and out of the structure, improving the noise immunity of the structure to room light and other noise sources. An adhesive 316 can be laminated or otherwise applied over at least a portion of the skin facing surface 302b to allow the structure to be releasable secured to either a closed eyelid or secured to a structure of a mask (not illustrated in Figures 3A-3C). The adhesive 316, can, for example, comprise a bio-compatible pressure sensitive adhesive that is selectively releasable from skin tissue (e.g., closed eyelid) without damage to the skin tissue. The adhesive should be transparent, at least to the wavelengths of light that will be emitted and returned to the device. The adhesive preferably has minimal or low index of refraction and preferably does not significantly introduce refraction or diffraction of light. The adhesive can be selected from hydrocolloid adhesives, synthetic rubber adhesives, natural rubber adhesives, silicone-based adhesives, acrylic based adhesives, PVC-based adhesives, and natural or artificial gelatins. A release liner can removably cover the pressure sensitive adhesive prior to use.

[0119] Figure 3C shows the device 300b (Figure 3B) overlying a portion of a closed eyelid 318 which itself overlies a portion of a cornea 320 of the eye, according to at least one illustrated implementation.

[0120] Figure 3C is representative of the attachment of the device 300b to an exterior or outer surface 318a of the closed eyelid 318 via the adhesive 316. It is noted that while Figure 3C generally illustrates portions of the eye and device 300b as flat, in the typically application the relevant portions of the eye (e.g., cornea 320 and portion of closed eyelid 318 overlying the cornea 320) will typically not be flat but rather may be convex or curved.

[0121] Figure 3D shows the device 300b to detect at least one of a pupillary characteristic(s), and, or an eye position of an eye having an iris and a pupil through a closed eyelid positioned overlying and on the exterior or outer surface 318a of the closed eyelid 318, better illustrating how the device 300b, or portion thereof, conforms to a curvature of at least a portion of the eye (e.g., cornea 320 and portion of closed eyelid 318 overlying the cornea 320), according to at least one illustrated implementation.

[0122] As previously noted, the substrate 302 is flexible or pliant and conformable to the exterior or outer surface 318a of the closed eyelid 318, for example when overlying such or even when adhered to the exterior or outer surface 318a of the closed eyelid 318.

[0123] Figure 3E schematically illustrates the device 300b attached to the exterior or outer surface 318a of the closed eyelid 318 via the adhesive 316 as illustrated in Figure 3C.

[0124] In Figure 3E, an iris 322 and pupil 324 formed by the iris 322 are illustrated. Light 326 (represented by broken line arrow) emitted by one of the LEDs 304 at a shallow angle emission is returned (e.g., reflected, refracted) from a portion of the iris 322 and detected by one of the light sensors 306. The shallow angle emission of the LEDs advantageously enhances scattering off light off of the iris 322. The light 326 emitted by one of the LEDs 304 can, for example, extend along a primary or principal axis of emission of the LED chip, so as not to enter the vitreous of the eye, for example at a shallow angle emission such that the primary or principal axis of emission is tangential to the portion of the eye, for instance tangential to the cornea 320 and / or iris 322.

[0125] It is noted that while Figure 3E generally illustrates portions of the eye and device 300b as flat for convenience of illustration, in the typically application the relevant portions of the eye (e.g., cornea 320 and portion of closed eyelid 318 overlying the cornea 320) will typically not be flat but rather may be convex or curved.

[0126] Figure 3F shows an eye 330, closed upper eyelid 318b and lower eyelid 318c with the device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B) positioned in front of the eye 330 and over the exterior or outer surface 318a of the closed upper and lower eyelids 318b, 318C. Figures 3F and 3G better illustrate the curvature of the relevant portions of the eye (e.g., cornea 320 and portion of closed eyelids 318b, 318c overlying the cornea 320) which may be convex or curved.

[0127] The eye 330 includes a cornea 320, an iris 322 positioned relatively behind the cornea, a pupil 324 formed by the iris 322 with aqueous humor 325, a lens 332, a vitreous cavity 334 which holds the vitreous 336 and the retina 338. The light emitters of the first plurality of light emitters 104 emit light 326 (represented by arrow, only two called out in Figure 3F) at a shallow angle emission, is returned (e.g., reflected, refracted) from a portion of the iris 322 and detected by one of the light sensors 108, 306 (represented as frustoconicals). The shallow angle emission of the light emitters of the first plurality of light emitters 104 advantageously enhances scattering of light off of the iris 322. The light 326 emitted by one of the light emitters 104 can, for example, extend along a primary or principal axis of emission e.g., arrow) of the light 326 of the LED chip, so as not to enter the vitreous 336 of the eye 330, for example at a shallow angle emission such that the primary or principal axis of emission is tangential to the portion of the eye 330, for instance tangential to the cornea 320 and / or iris 322.

[0128] The light sensors 108 are positioned on the substrate of the device 100, 300a, 300b to be located generally aligned with the pupil 324. The light emitters of the second plurality of light emitters 106 can be distributed across the substrate, some generally aligned with the pupil 324 and some not aligned or overlying the pupil 324 when the device 100, 300a, 300b is positioned over the upper and lower closed eyelids 318b, 318c.

[0129] In some implementations, the device 100 (Figures 1A-1C), 300a (Figure 3A), 300b (Figure 3B) is sized to cover one eyelid of a pair of closed eyelids of one eye. The device can be secured (e.g., adhesive, bio-compatible adhesive, bio-compatible pressure sensitive adhesive) to one eyelid of a pair of closed eyelids of one eye. The device can transmit light through the one eyelid of a pair of closed eyelids of one eye. The device receives light that passes through the one eyelid of a pair of closed eyelids of one eye.

[0130] In some implementations, the device the device 100 (Figures 1A-1C), 300a (Figure 3 A), 300b (Figure 3B) is sized to cover both eyelids of a pair of closed eyelids of one eye. The device can be secured (e.g., adhesive, bio-compatible adhesive, biocompatible pressure sensitive adhesive) to both eyelids of a pair of closed eyelids of oneeye. The device can transmit light through both eyelids of a pair of closed eyelids of one eye. The device receives light that passes through both eyelids of a pair of closed eyelids of one eye.

[0131] Figure 3G schematically illustrates a simplified geometrical model of an eye 330 and some representative angles, according to at least one illustrated implementation.

[0132] Any light with a source (Lambertian) which is 6.5 degrees or so from the center of the optical axis hits the side of the lens in the simplified geometrical eye model before it passes into the vitreous for a 4mm pupil. For any light source within the cone, that the difference of the position and emission angles needs to stay below that sum (so that none of the rays go more acutely than the 6.5 degrees).

[0133] In most unconscious or anesthetized individuals will be given drugs that will often constrict their pupils.. At a representative extreme (e.g., 8 mm) that angle is 5.6 degrees.

[0134] Figures 4A, 4B, 4C, 4D, 4E, and 4F are cross-sectional views sequentially illustrating a manufacturing process to manufacture a device such as the device 300b illustrated in Figures 3B-3E, according to at least one illustrated implementation.

[0135] As illustrated in Figure 4A, the manufacturing process starts with a substrate, for instance a polyimide substrate or layer 308. The polyimide substrate or layer 308 may include a copper cladding or an electrically conductive substrate or layer (e.g., copper foil layer 310) can be applied on the polyimide substrate or layer 308. The copper cladding or an electrically conductive substrate or layer (e.g., copper foil layer 310) is patterned (e.g., masked and etched) to form one or more circuit traces.

[0136] As illustrated in Figure 4B, the manufacturing process deposits and patterns (e.g., masked and etched) and solder mask layer 312 on the patterned copper cladding or patterned copper foil layer 310.

[0137] As illustrated in Figure 4C, the manufacturing process positions LEDs 304 and light sensors 306 on the patterned copper cladding or patterned copper foil layer 310. Such can be done manually or using conventional pick and place machinery.

[0138] As illustrated in Figure 4D, the manufacturing process applies (e.g., laminates, coats) an adhesive 316 over at least a portion of the skin facing surface 302b to allow the structure to be releasable secured to either a closed eyelid or secured to a structure of a mask. As previously noted the adhesive 316, can, for example, comprise a bio-compatible pressure sensitive adhesive that is selectively releasable from skin tissue (e.g., closed eyelid) without damage to the skin tissue.

[0139] As illustrated in Figure 4E, the manufacturing process applies (e.g., laminates, fastens, secures) an opaque layer film 314 can be laminated or otherwise secured on the exterior facing surface 302a. As previously noted, the opaque layer film 314 can advantageously reduce a leakage of light into and out of the structure.

[0140] As illustrated in Figure 4F, the structure of the device 300b is illustrated at the completion of the manufacturing process.

[0141] Figure 5A shows a patch 500a employing a device such as the device 300a as illustrated in Figure 3 A and which can be placed on, or even adhered to, a closed eyelid, according to at least one illustrated implementation.

[0142] In this implementation, a device 300a is incorporated into a patch 500a, for example an eyepatch, the device 300a operable to detect at least one of physiological eye character! stic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye having an iris and a pupil through a closed eyelid. The patch 500a can placed on an outer surface of the closed eyelid of a subject 502 (e.g., patient) and even secured thereto for example via an adhesive. It is noted that when placed on the closed eyelid, the patch 500a will place the LEDs and photodiodes proximate or even in contact with the closed eyelid.

[0143] As illustrated, the patch 500a can have a shape or form factor and, or a size that closely resembles the shape and, or size of a closed eyelid. For example, the patch 500a can have an oval shape, with dimensions that match or approximate the outer dimensions of an average adult eyelid, and, or that match or approximate the outer dimensions an average child eyelid. Patches 500a can be provided in different sizes, for example in kits with a distribution of sizes. Providing patches 500a with a shape and, or size that approximates that of a closed eyelid facilitates correct placement of the patch 500a on the closed eyelid. Such can be particularly beneficial in emergency situations and, or when placed by lay people. Correct placement ensures that the light emitter and, or light sensors on the substrate 302 are correctly positioned and, or oriented with respect to the eye underlying the closed eyelid. Providing patches 500a with a shape and, or size that approximates that of a closed eyelid also ensures that ambient light form the environment is effectively blocked by the patch 500a which is preferably opaque. The patch 500a can optionally include an adhesive 506 on the eyelid facing surface of the patch 500a, with or without a release liner 508 (illustrated removed from the adhesive 506). Various options for adhesives are described herein.

[0144] The device 100 in the form of an eyelid mounted patch 500a constitutes a contact imager. Direct contact with, and even attachment to, a closed eyelid provides numerous benefits over locating light emitters and light sensors spaced from the subject (e.g., spaced more than 2 cm, 100 cm or even further from the subject). Positioning the device 100 on the closed eyelid, especially with an adhesive, can advantageously reduce scatter of light by the eyelid (e.g., scatter by an outer surface of the closed eyelid).Positioning the patch 500a on the closed eyelid minimizes a distance that light needs to travel so reduces loss of intensity of light as it travels to and returns from the eye via the closed eyelid, reducing a spread of light over distance and hence reducing a diameter of a cone of the light. Such thereby requires fewer light emitters and, or light sensors to achieve a given level or intensity of illumination and, or a given level of sensitivity as compared to systems that are spaced from the eyelid(s), (e.g., systems not in physical contact with the eyelid(s)). Such advantageously results in improved signal-to-noise ratios (SNR). Such also simplifies the optical path of light to and from the eye. Using fewer light emitters and, or light sensors also advantageously reduces the amount of energy consumed, and the amount of heat generated by the device 100. Lower energy consumption means that the device 100 can be powered by a battery or ultra- or supercapacitor. Less heat dissipation also means less heat transferred to the skin of the subject. This can be particularly beneficial as blood is known to be a good heat sink and excessive heat applied to the face can have various adverse consequences. Positioning the patch 500a on the closed eyelid advantageously reduces and substantially eliminates relative motion between the eye and the light emitters and light sensors as the device 100 will move with the head of the subject (e.g., patient). Positioning the device 100 on the closed eyelid reduces or even eliminates possible alignment errors as a small angular misalignment will not result in a large spatial misalignment given the extremely short distance between the eye and the light emitters and light sensors. Positioning the patch 500a on the closed eyelid can advantageously eliminate the need for interstitial optics, reducing the number of elements, simplifying the optical path and reducing a length of the optical path, and thereby reducing a cost and a size of the device, which in turn increases a pliability and, or compliance and, or conformability of the device 100 allowing such to more closely conform to the contour of the eye underling the closed eyelid. Positioning the patch 500a on the closed eyelid also advantageously improves the ability to block stray light (e.g., ambient light), for instance where the substrate or another portion of the device 100 is opaque. This can be particularly advantageous in medicalsettings like in the intensive care unit (ICU) or operating room (OR) where very bright light is typically employed, but would also be advantageous in other settings like in a clinician’s office or outdoors (e.g., in the field; battlefield, accident sites, sports events) where the device 100 may be used to treat victims of trauma or those experiencing other medical situations or aliments such as loss of consciousness. Positioning the patch 500a on the closed eyelid, especially with an adhesive can advantageously retain the eyelid in a closed position or state, thereby reducing or eliminating the risk of corneal injury (e.g., abrasion or tear for instance related to dry eye). Such can also advantageously smooth the closed eyelid which would otherwise have several wrinkles and thereby reduce the scattering of light traveling toward the eye through the closed eyelid and, or light returning from the eye through the closed eyelid. Such can further advantageously prevent the opening of the closed eyelid (e.g. voluntary opening, involuntary blinking), thereby eliminating temporal artifacts in the returned light detection.

[0145] Portions of the patch 500a can be shaped and, or sized, to be complementary to portions of the face such that a form factor of the patch 500a ensures that the LEDs and light sensors are correctly positioned and oriented with respect to the eye. For example, the patch 500a can have a profile thereof that closely matches that of a closed eyelid, to correctly position and orient the LEDs and light sensors with respect to the eye when the patch 500a is placed on a closed eyelid of a subject. In some implementations, the device (e.g., in the form of two patches) can transmit light through the eyelids of a pair of closed eyelids of both eyes. The device receives light that passes through the closed eyelids of the pair of closed eyes. Where two patches are employed for a single subject, at least one of the patches can communicate with the other one or the patches, the patches can communicate with one another, or the patches each communicate with a processor-based device (e.g., smartphone, tablet computer) that is physically distinct from the patches. Communicates can employ wireless communications including radios, receivers, transmitters and antennas, light-based communications for instance LED-receiver pairs, or even wired communications. The use of two patches can advantageously allow the physiological eye characteristic(s) and, or eye position of both of the eyes to be compared to one another for consistency, which aids in assessing medical condition or rendering a diagnosis.

[0146] Figure 5B is an isometric view of a mask 500b employing a device such as the device 300a as illustrated in Figure 3A, according to at least one illustratedimplementation.

[0147] In this implementation, a pair of devices 300a are incorporated into a mask 500b, for example a face mask or sleeping mask, the devices 300a operable to detect at least one of a pupillary characteristic, and, or an eye position of an eye having an iris and a pupil through a closed eyelid. The mask 500b can be worn by a subject 502 (e.g., patient), covering the eyes of the subject 502, and positioning each device 300a of the pair of devices 300a over respective ones of the eyes of the patient. Portions of the mask 500b can be shaped and, or sized, to be complementary to portions of the face such that a form factor of the mask 500b ensures that the LEDs and light sensors are correctly positioned and oriented with respect to the eyes. For example, the mask 500b can have a concavity in a profile thereof that closely accommodates a nose of a subject, to correctly position and orient the LEDs and light sensors with respect to the eyes when the mask 500b is placed on a face or head of a subject. It is noted that when worn, the masks 500b will place the LEDs and light sensors (e.g., photodiodes) anywhere from a few hundred micros, to a few millimeters to a centimeter or slightly more away from the eyelids, and thus the LEDs and photodiodes will typically not be adhered to the eyelids nor necessarily touching the eyelids. The device (e.g., in the form of a mask 500b) can transmit light through the eyelids of a pair of closed eyelids of both eyes. The device receives light that passes through the closed eyelids of the pair of closed eyes. The mask 500b can have all or some processing on-board and, or can communicate with a processor-based device (e.g., smartphone, tablet computer) that is physically distinct from the mask 00b.Communicates can employ wireless communications including radios, receivers, transmitters and antennas, light-based communications for instance LED-receiver pairs, or even wired communications. The use of a mask 500b can advantageously allow the physiological eye characteristic(s) and, or eye position of both of the eyes to be compared to one another for consistency, which aids in assessing medical condition or rendering a diagnosis. Additionally, or alternatively use of a mask 500b can advantageously allow the physiological eye characteristic(s) and, or eye position of both of the eyes to be compared to one another for consistency, where differences in an otherwise healthy subject (e.g., during a sleep study) may indicate that the mask has shifted on the face of the subject and the data being collected may no longer be reliable.

[0148] The device 100 in the form of a mask 500b (e.g., sleep mask) essentially replicates a contact imager. Very close placement (e.g., 2 cm or less) to the closed eyelid(s) provides numerous benefits over locating light emitters and light sensors spaced from the subject (e.g., spaced more than 2 cm, 100 cm or even further from the subject).Positioning the device 100 close to the closed eyelid can advantageously reduce scatter of light by the eyelid (e.g., scatter by an outer surface of the closed eyelid). Positioning the device close to the closed eyelid minimizes distance that light needs to travel so reduces loss of intensity of light as it travels to and returns from the eye via the closed eyelid, reducing a spread of light over distance and hence reducing a diameter of a cone of the light. Such thereby requires fewer light emitters and, or light sensors to achieve a given level or intensity of illumination and, or a given level of sensitivity as compared to systems that are spaced from the eyelid(s), (e.g., systems not in close proximity, for instance 2 cm or less, with the eyelid(s)). Such advantageously results in improved signal-to-noise ratios (SNR). Such also simplifies the optical path of light to and from the eye. Using fewer light emitters and, or light sensors also advantageously reduces the amount of energy consumed, and the amount of heat generated by the device 100. Lower energy consumption means that the device 100 can be powered by a battery or ultra- or supercapacitor. Less heat dissipation also means less heat transferred to the skin of the subject. This can be particularly beneficial as blood is known to be a good heat sink and excessive heat applied to the face can have various adverse consequences. Positioning the mask 500 on the head advantageously reduces and substantially eliminates relative motion between the eye and the light emitters and light sensors as the device 100 will move with the head of the subject (e.g, patient). Positioning the device 100 close to the closed eyelid (e.g, 2 cm or less) reduces or even eliminates possible alignment errors as a small angular misalignment will not result in a large spatial misalignment given the extremely short distance between the eye and the light emitters and light sensors. Positioning the device 100 close to the closed eyelid can advantageously eliminate the need for interstitial optics, reducing the number of elements, simplifying the optical path and reducing a length of the optical path, and thereby reducing a cost and a size of the device, which in turn increases a pliability and, or compliance and, or conformability of the device 100.Positioning the device 100 close to the closed eyelid also advantageously improves the ability to block stray light (e.g., ambient light), for instance where the mask, the substrate or another portion of the device 100 is opaque. This can be particularly advantageous in medical settings like in the intensive care unit (ICU) or operating room (OR) where very bright light is typically employed, but would also be advantageous in other settings like in a clinician’s office or outdoors (e.g., in the field; battlefield, accident sites, sports events) where the device 100 may be used to treat victims of trauma or those experiencing other medical situations or aliments such as loss of consciousness. In some implementations,the mask can advantageously retain the eyelid in a closed position or state, thereby reducing or eliminating the risk of corneal injury (e.g., abrasion or tear for instance related to dry eye). Such can also advantageously smooth the closed eyelid which would otherwise have several wrinkles and thereby reduce the scattering of light traveling toward the eye through the closed eyelid and, or light returning from the eye through the closed eyelid. Such can further advantageously prevent the opening of the closed eyelid (e.g. voluntary opening, involuntary blinking), thereby eliminating temporal artifacts in the returned light detection.

[0149] Figure 5C shows a mask 500c worn by a subject 502 and a processor-based device 510c wirelessly communicatively coupled to the mask 500c, according to at least one illustrated implementation. The mask 500c is illustrated in Figure 5C as used as part of a sleep study, for example a sleep study conducted in a home setting or in a clinical setting. While illustrated used as part of a sleep study, the mask 500c can be used in a wide variety of applications and environments.

[0150] The mask 500c includes one or more devices 100, 300 (not called out in Figure 5C), such as the device 100, 300 illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D. The mask 500c may, for example include two instances of the device 100, 300, positioned to be aligned and oriented with respective ones of the eyes of the subject 502 when the mask 500c is worn on a face 512 of the subject 502. The mask 500c may include a concavity or contour 514 in a profile thereof or that is sized and shaped to accommodate a portion of a nose 516 of the subject 502, and which facilitates the correct alignment and orientation of the mask 500c on the face 512 of the subject 502 and consequently facilitates the correct alignment and orientation of the devices 100, 300 with respect to the closed eyes of the subject 502.

[0151] The mask 500c includes one or more communications systems (e.g., radios, transceivers, receivers, transceivers, antennas) that provide wireless (e.g., RF, microwave frequency) communications with the processor-based device 510c. There can be a single communications system for all of the devices 100, 300, or a respective communications system for each device 100, 300. The communications system of the mask 500c provides information or data from the mask 500c to the processor-based device 510c for processing. The information or data provided from the mask 500c can be raw information or data as collected by the sensors (e.g., light sensors, position sensors, temperature sensors, sweat sensors, pulse sensors, blood oxygen sensors), or can be information or data that is at least partially processed by circuitry of the mask 500c. The processor-baseddevice 510c is illustrated as a smartphone, which can have one or more dedicated applications (i.e., executable instructions) to process the information or data provided from the mask 500c, for example assessing a condition of the subject 502 or autonomously generating a diagnosis of the subject 502, or otherwise providing visual and, or aural indications of physiological eye characteristic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye, sensor readings, pupil sizes, pupil reflexes, and, or trends in such, and, or assessed conditions or diagnoses.

[0152] Figure 5D shows a mask 500d worn by a subject 502, the mask including an integral user interface (UI), according to at least one illustrated implementation. The mask 500d is illustrated in Figure 5C as used in a combat situation, the subject 502 wounded and a medical care provider or other aid rendering individual 503 using the UI, that is part of the mask 500d, in assessing and, or treating the subject 502. While illustrated used in a combat situation, the mask 500d can be used in a wide variety of applications and environments, for example at the scene of an accident or any place in which a subject is found unconscious, nonresponsive, or confused.

[0153] The mask 500d includes one or more devices 100, 300 (not called out in Figure 5C), such as the device 100, 300 illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D. The mask 500d may, for example include two instances of the device 100, 300, positioned to be aligned and oriented with respective ones of the eyes of the subject 502 when the mask 500d is worn on a face 512 of the subject 502. The mask 500d may include a concavity or contour (not called out in Figure 5D) in a profile thereof or that is sized and shaped to accommodate a portion of a nose (not called out in Figure 5D) of the subject 502, and which facilitates the correct alignment and orientation of the mask 500d on the face 512 of the subject 502 and consequently facilitates the correct alignment and orientation of the devices 100, 300 with respect to the closed eyes of the subject 502.

[0154] The mask 500d includes one or more user interfaces that are visible from an exterior of the mask 500d. For example, the mask 500d can include one or more displays 520a, 520b (e.g., liquid crystal displays (LCDs), LEDs, OLEDs, QLEDs, micro-LEDs). As illustrated, the mask 500d includes two displays 520a, 520b, one display for each eye. The displays 520a, 520b can be integral to the mask 500d, and can be carried on an exterior surface of the mask 500d, or under a protective transparent or translucent layer of the mask 500d, such that information presented or displayed by the displays 520a, 520b are visible to the medical care provider or other aid rendering individual 503. There canbe a single display 520a, 520b for all of the devices 100, 300, or a respective display 520a, 520b for each device 100, 300. The displays 520a, 520b of the mask 500d provide information or data from the mask 500d to the medical care provider or other aid rendering individual 503. The information or data provided from the mask 500d can be raw information or data as collected by the sensors (e.g., light sensors, position sensors, temperature sensors, sweat sensors, pulse sensors, blood oxygen sensors), or can be information or data that is at least partially processed by circuitry of the mask 500d.Preferably, the information or data provided presented by the displays 520a, 520b of the mask 500c can be an indication of a condition of the subject 502 or a diagnosis of the subject 502 as determined by the circuitry (e.g., processor) of the mask 500d. Such can, for example, take the form of simple indications, for instance colors (red, green), Boolean values, graphical displays of pupil size and eye direction, numerical values, and, or textual messages (e.g., seek emergency assistance; concussion detected, traumatic brain injury detected). Alternatively, the medical care provider or other aid rendering individual 503 can employ the information or data provided from the mask 500d, for example in assessing a condition of the subject 502 or generating a diagnosis of the subject 502, for instance comparing the indication for one eye with the indications for the other eye of the subject 502.

[0155] Figure 5E shows a mask 500e worn by a subject 502 and a processor-based device 510e wiredly communicatively coupled to the mask 500e, according to at least one illustrated implementation. The mask 500e is illustrated in Figure 5E as used in an intensive care environment. While illustrated used in an intensive care environment, the mask 500d can be used in a wide variety of applications and environments, for example in an operating room or operating theater.

[0156] The mask 500e includes one or more devices 100 (two called out in Figure 5E), such as the device 100, 300 illustrated in Figures 1A-1D, 2A, 2B, 3A-3D. The mask 500e may, for example include two instances of the device 100, 300, positioned to be aligned and oriented with respective ones of the eyes of the subject 502 when the mask 500e is worn on a face 512 of the subject 502. The mask 500e may include a concavity or contour 514 in a profile thereof or that is sized and shaped to accommodate a portion of a nose 516 of the subject 502, and which facilitates the correct alignment and orientation of the mask 500e on the face 512 of the subject 502 and consequently facilitates the correct alignment and orientation of the devices 100, 300 with respect to the closed eyes of the subject 502.

[0157] The mask 500d includes one or more cables 522 that provide wired (e.g., Universal Serial Bus, optical fiber) communications with the processor-based device 510e. There can be a single communications system for all of the devices 100, 300, or a respective communications system for each device 100, 300. The communications system of the mask 500d provides information or data from the mask 500e to the processor-based device 510e for processing. The information or data provided from the mask 500e can be raw information or data as collected by the sensors (e.g., light sensors, position sensors, temperature sensors, sweat sensors, pulse sensors, blood oxygen sensors), or can be information or data that is at least partially processed by circuitry of the mask 500e. The processor-based device 510e is illustrated as a console (e.g., patient or bedside console), which can have one or more dedicated applications (i.e., executable instructions) to process the information or data provided from the mask 500e, for example assessing a condition of the subject 502 or autonomously generating a diagnosis of the subject 502, or otherwise providing visual and, or aural indications of physiological eye characteristic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye, sensor readings, pupil sizes, pupil reflexes, and, or trends in such, and, or assessed conditions or diagnoses.

[0158] Figure 6A shows a system 600a to detect at least one of a pupillary characteristic, and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0159] The system 600a can include one or more processors 602 (e.g., microprocessors, microcontrollers, central processing units (CPUs), graphical processing units (GPUs), digital signal processing units (DSPS), application specific integrated circuit (ASIC), field programmable gate arrays (FPGAs) or other circuity that executes logic (e.g., processorexecutable instructions). The system 600a can include one or more storage media 604, for instance one or more nonvolatile storages such as read only memory (ROM), electrically programmable read-only memory (EPROM), electrically erasable and programmable read only memory (EEPROM), Flash memory, solid state drive, magnetic or optical cards, spinning storage media such as a hard disk drive or optical disk drive, one or more volatile storages such as random access memory (RAM), and, or one or more registers that are part of or otherwise associated with the processors 602. The storage media 604 can store processor-executable instructions and data, the processor-executableinstructions which, when executed by the at least one processor, cause the processor(s) 602 to execute various methods, algorithms and other logic described herein.

[0160] The system 600a can include one or more drivers 606 (only two called out) that apply drive signals (e.g., drive current) to the LEDs 304 (Figures 3A, 3B) (e.g., first plurality of light sources or light emitters 104 and the second plurality of light sources or light emitters 106 (Figures 1 A-1C)). The drivers 606 can, for example, take the form of commercially available LED driver circuits or current sources. As illustrated, there may be one driver for each LED 304.

[0161] The system 600a can include one or more amplifiers 608 (only two called out) that amplify signals from the light sensors 306 (Figures 3A, 3B) (e.g., plurality of light sensors 108 (Figures 1A-1C)). The amplifiers 608 can, for example, take the form of commercially available photodetector or photodiode amplifiers. As illustrated, there may be one amplifier 608 for each light sensor 306 (e.g., photodiode).

[0162] The system 600a can include one or more wireless communications interfaces 610, for example one or more radios, transceivers, receivers that wirelessly transmit information between (e.g., to and / or from) the processor(s) and the apparatus, systems and / or components that are distinctly separate from the device 100, 300a, 300b. The wireless transmission can employ signals transmitted in the radio frequency range or microwave frequency range of the electromagnetic spectrum. Thus, the system 600a can include one or more radios, transceivers, receivers and associated antennas communicatively coupled to the processor(s).and operable to wirelessly transmit the signals. Optionally, the wireless transmission can employ signals transmitted in the optical (e.g., white light, infrared, SWIR ultraviolet frequency ranges) range of the electromagnetic spectrum. Thus, the system 600a can include one or more optical transmitters and, or optical receivers, communicatively coupled to the processor(s). The wireless communications interfaces 610 can, for example, provide communications with one or more computer systems (e.g., Figures 6C and 7).

[0163] The system 600a can include one or more power supplies 612, for example a DC power supply, for instance an inductive power source that receives power via magnetic field fluctuations or electric field fluctuations, with suitable voltage and current conversion and regulation circuitry (e.g., rectifier, step up / step down converter).Additionally or alternatively, the power supply 612 can include a primary battery, a secondary battery and / or a super- or ultra-capacitor, with or without suitable voltage and current regulation circuitry.

[0164] The processor(s) 602, drivers 606, amplifiers 608, wireless communications interfaces 610, and / or power supply 612 can all be part of the device 100, 300a, 300b, for example mounted to the substrate 102, 302 thereof. Alternatively, one or more of those components can be separate from the device 100, 300a, 300b, for example not mounted or otherwise physically coupled to the substrate 102, 302 thereof. For example, a processor can be located separately from the device and communicatively coupled therewith via a wireless communications interface similar to the wireless communications interface 610.

[0165] Figure 6B shows a system 600b to detect at least one of physiological eye character! stic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0166] The system 600b can include one or more processors 602 (e.g., microprocessors, microcontrollers, central processing units (CPUs), graphical processing units (GPUs), digital signal processing units (DSPS), application specific integrated circuit (ASIC), field programmable gate arrays (FPGAs) or other circuity that executes logic (e.g., processorexecutable instructions). The system 600b can include one or more storage media 604, for instance one or more nonvolatile storages such as read only memory (ROM), EEPROM, Flash memory, solid state drive, spinning storage media such as a hard disk drive or optical disk drive, one or more volatile storages such as random access memory (RAM), and, or one or more registers that are part of or otherwise associated with the processors. The storage media 604 can store processor-executable instructions and data, the processor-executable instructions which, when executed by the at least one processor, cause the processor(s) 602 to execute various methods, algorithms and other logic described herein.

[0167] The system 600b can include one or more drivers 606 (only two called out) that apply drive signals (e.g., drive current) to the LEDs 304 (Figures 3A, 3B) (e.g., first plurality of light sources or light emitters 104 and the second plurality of light sources or light emitters 106 (Figures 1 A-1C)). The drivers 606 can, for example, take the form of commercially available LED driver circuits or current sources. As illustrated, there may be one driver for each LED 304.

[0168] The system 600b can include one or more amplifiers 608 (only two called out) that amplify signals from the light sensors 306 (Figures 3A, 3B) (e.g., plurality of light sensors 108 (Figures 1A-1C)). The amplifiers 608 can, for example, take the form ofcommercially available photodetector or photodiode amplifiers. As illustrated, there may be one amplifier 608 for each light sensor 306 (e.g., photodiode).

[0169] The system 600b can include one or more wireless communications interfaces 610, for example one or more radios, transceivers, receivers that wirelessly transmit information between (e.g., to and / or from) the processor(s) and the apparatus, systems and / or components that are distinctly separate from the device 100, 300a, 300b. The wireless transmission can employ signals transmitted in the radio frequency range or microwave frequency range of the electromagnetic spectrum. Thus, the system 600b can include one or more radios, transceivers, receivers and associated antennas communicatively coupled to the processor(s).and operable to wirelessly transmit the signals. Optionally, the wireless transmission can employ signals transmitted in the optical (e.g., white light, infrared, SWIR ultraviolet frequency ranges) range of the electromagnetic spectrum. Thus, the system 600b can include one or more optical transmitters and, or optical receivers, communicatively coupled to the processor(s). The wireless communications interfaces 610 can, for example, provide communications with one or more computer systems (e.g., Figures 6C and 7).

[0170] The system 600b can include one or more power supplies 612, for example a DC power supply, for instance an inductive power source that receives power via magnetic field fluctuations or electric field fluctuations, with suitable voltage and current regulation and / or conversion circuitry (e.g., rectifier, step up / step down converter). Additionally or alternatively, the power supply 612 can include a primary battery, a secondary battery and / or a super- or ultra-capacitor, with or without suitable voltage and current regulation and conversion circuitry.

[0171] The processor(s) 602, drivers 606, amplifiers 608, wireless communications interfaces 610, and / or power supply 612 can all be part of the device 100, 300a, 300b, for example mounted to the substrate 102, 302 thereof. Alternatively, one or more of those components can be separate from the device 100, 300a, 300b, for example not mounted or otherwise physically coupled to the substrate 102, 302 thereof. For example, a processor can be located separately from the device, and communicatively coupled therewith via a wireless communications interface similar to the wireless communications interface 610.

[0172] The system 600b differs from the system 660a (Figure 6A) by adding a secondary battery and / or battery charge management circuitry 614. Such can allow a secondary battery to be recharged (e.g., trickle charging, fast charging), allowing extended use of the device without requiring removal from the patient.

[0173] Figure 6C shows a system 600c to detect at least one of physiological eye character! stic(s) (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of an eye having an iris and a pupil through a closed eyelid using a device such as that illustrated in Figures 1 A-1D, 2A, 2B, 3A-3D, according to at least one illustrated implementation.

[0174] The system 600c is similar, and in some respects identical, to the system 600a (Figure 6A) and, or the system 600b (Figure 6B). The systems 600a, 600b, 600c include light emitters, light sensors or detectors, processors (e.g., microcontrollers), amplifiers, analog-to-digital converters (ADCs), ADC channels, and wireless or wired interfaces or connectors or links. Only significant differences between the system 600c and the systems 600a, 600b will be discussed immediately below in the interest of conciseness.

[0175] The system 600c communicatively employs one or more cables 616 to communicatively couple the processor 602 to a processor-based system 618 (e.g., computer system) that is separate and distinct from the device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B). In other implementations, any of the systems 600a, 600b, 600c can be wireless communicatively coupled to the processor-based system 618 (e.g., computer system) that is separate and distinct from the device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B).

[0176] The processor-based system 618 can be employed with any of the systems 600a, 600b, 600c.

[0177] Figure 7 shows a processor-based system 700 according to at least one illustrated implementation. The processor-based system 700 can separate and distinct from the device 100 (Figures 1A-1C), 300a (Figure 3A), 300b (Figure 3B). The processor-based system 700 can be employed with any of the systems 600a, 600b, 600c. The processor-based system 700 can, for example, take the form one or more computing systems (e.g., digital computing system, quantum computing system). The processorbased system 700 can, for example, include one or more trained artificial neural networks (ANNs), perform machine-learning or implement other artificial intelligence techniques depending on the processor-executable instructions executed by the processor(s) thereof.

[0178] The processor-based system 700 may include one or more processors 730, for example, one or more of: one or more microcontrollers, one or more microprocessors, 730a one or more central processing units, one or more digital signal processors (DSPs) 730b, one or more graphics processing units (GPUs) 730c, one or more application specific integrated circuits (ASICs) 730d, one or more field programmable gate arrays(FPGAs) 73 Oe, one or more machine-learning systems or artificial neural networks 73 Of and / or one or more programmable logic controllers (PLCs) (not shown).

[0179] The processor-based system 700 may include one or more nontransitory storage media, communicatively coupled to the processor(s) 730, for example, one or more nonvolatile storage media and / or one or more volatile storage media, for example a system memory 732 that includes one or more of one or more read only memories (ROMs) 734, one or more random access memories (RAMs) 736, one or more magnetic disk 738 and associated drives 740, one or more optical disk 742 and associated drives 744, one or more solid state drives 746 (e.g., FLASH memory), one or more cache memories, and / or one or more registers (not shown) of one or more processors 730. The processor-based system 700 may include one or more communications channels 748 (e.g., buses) that communicatively couple the processor(s) with the storage media. The processor-based system 700 may include one or more communications ports, for example one or more wired communications ports 750 for communications via wired or optical connections (e.g, cable 616 of Figure 6C), wireless communications ports 752 (e.g., WiFi and / or Bluetooth radios and associated antennas 754; infrared transceivers, for instance via communications interface 610 of Figures 6A and 6B) that provide for communications between the processor-based system 700 and external devices.

[0180] A user interface system 766 may, for example, include one or more of one or more display screens, one or more touch-sensitive display screens 768, one or more speakers 770, one or more microphones 772, one or more keyboards 774, and / or one or more pointer devices 776 (e.g., computer mouse, trackpad, trackball). The components of the user interface system 766 are communicatively coupled (e.g., wired, optical, wireless or radio) with the processor(s) 730 via one or more peripheral interfaces 780a, 780b to provide user input to the processor(s) 730 and to receive output from the processor(s) 730 to be presented to a user. In particular, the processor(s) 730 may execute processorexecutable instructions that cause the processor(s) to cause devices to present a user interface (e.g., a graphical user interface), for instance via a touch-sensitive display screens 768 (aka, touch screen display). Various user interface elements are illustrated and described herein. Some or all of the display and state indications can be visible from an exterior of the eyepatch or mask, for example a display can be carried on or under the exterior surface of the eye patch or mask, e.g. as a micro-LED display.

[0181] The user interface (UI) system 766 can include one or more user interface (UI) components, for example one or more switches, triggers, display screens (e.g, LCDdisplay), lights (e.g., LEDs), speakers, microphones, haptic engines, graphical user interfaces (GUIs) with via a touch-sensitive display screen which displays user-selectable icons operable to allow input to the processor-based system 700 and / or output from the processor-based system 700. The UI components allow a user to control operation and / or optionally to receive information. For example, a user may press a button, key or trigger, or can use eye movements to provide input to the processor-based system 700.

[0182] Various implementations described herein may include, or may operate by, logic or a number of components, or mechanisms. Circuitry is a collection of circuits implemented in tangible entities that include hardware (e.g., simple circuits, gates, logic, etc.). Circuitries include circuit elements that may, alone or in combination, perform specified operations when operating. In an example, hardware of the circuitry may be immutably designed to carry out a specific operation (e.g., hardwired). In an example, the hardware of the circuitry may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) including a computer-readable medium physically modified (e.g., magnetically, electrically, moveable placement of invariant massed particles, etc.) to encode instructions of the specific operation.

[0183] The instructions enable embedded hardware (e.g., the execution units or a loading mechanism) to create members of the circuitry in hardware via the variable connections to carry out portions of the specific operation when in operation.Accordingly, the computer-readable medium is communicatively coupled to the other components of the circuitry when the device is operating.

[0184] In an example, one or any combination of the hardware processor(s) 730, system memory 732, magnetic disk 738, optical disk 742 and / or solid state drive 746 constitute machine-, computer- or processor-readable media. The terms "machine-readable media", “computer- readable media” and “processor-readable media” may include a single medium or multiple media (e.g., a centralized or distributed database, and / or associated caches and servers) operable to store one or more computer- or processor-executable instructions. The terms "machine-readable media", “computer- readable media” and “processor-readable media” include any medium that is capable of storing, encoding, or carrying instructions for execution by the processor(s) 730 and that cause the processor(s) 730 to perform any one or more of the techniques of the present disclosure, or that is capable of storing, encoding or carrying data structures used by or associated with such instructions. Non-limiting examples of terms "machine-readable media", “computer-readable media” and “processor-readable media” include solid-state memories, andoptical and magnetic media. The terms "machine-readable media", “computer- readable media” and “processor-readable media” do not include non-transitory propagating signals. Examples of nontransitory machine-readable media, nontransitory computer-readable media and nontransitory processor-readable media include non-volatile memory, such as semiconductor memory devices (e.g., Electrically Programmable Read-Only Memory (EPROM), Electrically Erasable Programmable Read-Only Memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; and CD-ROM and DVD-ROM disks.

[0185] Communications can utilize any one of a number of transfer protocols (e.g., frame relay, internet protocol (IP), transmission control protocol (TCP), user datagram protocol (UDP), hypertext transfer protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), mobile telephone networks (e.g., cellular networks), Plain Old Telephone (POTS) networks, and wireless data networks (e.g., Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards known as WiFi®, IEEE 802.16 family of standards known as WiMax®), IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, among others. In an example, interface devices may include one or more physical jacks e.g., Ethernet, coaxial, or phonejacks) or one or more antennas to connect to the communications network 826. In an example, interface devices may include a plurality of antennas to wirelessly communicate using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) techniques. The term "transmission medium" shall be taken to include any tangible medium that is capable of storing, encoding or carrying instructions for execution by the processor-based system 700, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

[0186] The processor(s) 730 of the processor-based system 700 are operable to execute logic, for example to execute one or more algorithms stored as process-executable instructions by the one or more nontransitory storage media. Suitable algorithms are set out herein, for example with reference to the various flow diagrams. Process-executable instructions may, for example, include a basic input / output operating system (BIOS) 756, for example stored in ROM 734.

[0187] Processor-executable instructions may, for example, include an operating system (OS) 758, for example stored in RAM 736 during execution. Process-executableinstructions may, for example, include one or more application programs 760. The applications program(s) can, for example, stored in RAM 736 during operation.

[0188] The applications program(s) can, for example, provide the logic that cause the processor(s) to processes, compute, calculate, or determine, or assist a human in determining, one or more of: i) a layout of components on a substrate 102 of a device (e.g., device lOOe), ii) one or more of physiological eye characteristic(s), and, or eye position for instance estimating gaze direction and pupil diameter (e.g., feeding photo sensor data to an algorithm for training, which can be used for any one or more of the devices 100, lOOd, lOOe described herein and, or assessing or determining a physiological or neural state or condition of a subject (e.g., human patient) based on detected pupillary response.

[0189] The locations or layout of the second plurality of light emitters 106 (e.g., IR LEDs) and the light sensors 108 (e.g., photosensors for instance photodetectors) can be optimized to maximize a sensitivity of the device lOOe, for example by maximizing a coverage of a region of interest (ROI). Each pair of light emitters 106 and light sensors 108 produces a single measurement which is sensitive to a particular spatially-localized area ( / .< ., sensitivity region) on a surface of the eye. The overall coverage region of the device lOOe is a union of these sensitivity regions, corresponding to all possible pair of light emitters 106 and light sensors 108. The layout of the light emitters 106 and light sensors 108 is optimized to maximize coverage over an ROI corresponding to physiologically realistic gaze directions. The optimizer iteratively adjusts light emitter 106 and light sensor 108 locations to maximize a coverage score, which is computed over the ROI, and which measures the area covered by local regions. A weighting function can used to ensure that, on average, each point in the ROI is as close as possible to a center of at least one sensitivity region. Optimization can be performed with a variety of iterative methods, including gradient descent, noisy (stochastic) gradient descent, and higher order Newton-type methods. Optimization can incorporate physical design constraints on the placement of the light emitters 106 and light sensors 108. The locations of the light emitters 106 and light sensors 108 can be initialized at random, or using any symmetric or asymmetric initial configuration.

[0190] Physiological eye characteristic(s) can, for example, include a proxy for pupil size, a pupil size and / or a pupillary reflex. Physiological eye character! stic(s), and, or eye position can advantageously be determined based on detection of light by the light sensors (e.g., photodetectors) where the detected light is light returned through the eyelidfrom the iris of the eye. Such can determine pupil size or determine a value that represents or is otherwise correlated to pupil size (e.g., an amount of light returned which is correlated to pupil size and hence a proxy for pupil size) without actually determining the pupil size itself. Such can determine how quickly pupil diameter changes, either by determining the pupil size at successive instances of time or by determining a value that represents or is otherwise correlated to pupil size ( / .< ., proxy for pupil size) at successive instances of time. Detecting a pupillary light reflex response can be based on a change in the physiological eye characteristic (e.g., pupil size or proxy thereof) via a change in the size of the inner periphery of the iris before and after triggering the pupillary light reflex via emission of the first plurality of light emitters. Thus, the detection of a physiological eye characteristic (e.g, pupil size or proxy thereof and, or a pupillary light reflex) can include: determining an amount of light returned from the eye, determining which light sensors detect light returned from the eye, and, or determining a size of an inner periphery of the iris and, or determining how quickly the size of the inner periphery of the iris changes. Alternatively, detecting a pupillary light reflex response can be based on a change in determining a value that represents or is otherwise correlated to pupil size at successive instances of time before and after triggering the pupillary light reflex via emission of the first plurality of light emitters.

[0191] Detection of a proxy of pupil size can advantageously employ a set of light detectors arrayed about an axis (e.g., an optical axis). Those light detectors that detect light returned from the eye via the closed eyelid and define a perimeter of the returned light, which sets a rough outside boundary of the pupil as light passing through the pupil not be reflexed back toward the light detectors. This approach provides a proxy of pupil size, and in some implementations can be converted into a measure of pupil size, while avoiding computationally costly and inefficient image processing to find boundaries in image data. The system can include one or more strain sensors or strain gauges, or other structures, to measure or otherwise assess a curvature of the eye and, or an eye position of the eye. Use of curvature or strain information from the flexible patch can be used as a data input to the algorithm determining eye position.

[0192] The amount of light returned from an eye through closed eyelid with be a function the amount of dilation of the pupil, since light passing through the pupil is not returned.

[0193] In some implementations, rather than directly measuring pupil size, at least one approach can determine pupil size based on a defined correlation between an amount oflight returned from the eye via the closed eyelid that is detected by the light sensors. This approach can result in a value for pupil size, while avoiding computationally costly and inefficient image processing to find boundaries in image data.

[0194] As noted above, rather than directly measuring pupil size, at least one approach can infer or use a value that is correlated to pupil size. Thus, it is not necessary to actually measure the size of the pupil, as the amount of light detected can serve as a proxy for pupil size. In some implementations, the system does not actually determine a pupil size but rather employs an amount of returned light that is detected by the light sensors as a proxy for pupil size. In doing so, the system can, for example, adjust the detected amount of light to account for characteristics of the skin (e.g., thickness, pigmentation). Thus, in some implementations, the system simply employs the amount of returned light detected as a proxy for pupil size without converting such to a corresponding size of the pupil, and can do so with or with adjusting for characteristics of the skin.

[0195] Evaluating parameters of pupillary light reflex include, but are not limited to evaluating one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline. Evaluating parameters of pupillary light reflex can also include comparing a response of one eye with a response of the other eye. Evaluating parameters of pupillary light reflex can also include comparing change in response over time to a set baseline. Evaluating parameters of pupillary light reflex can also include comparing such against population averages.

[0196] The system can automatically or autonomously replicate a “swinging flashlight” test. For example, the processor can control the light emitters and light sensors to measure a consensual response of one eye to a light stimulus delivered to the other eye, while it is still dilating from a prior direct response to an earlier light stimulus delivered to the that eye, and then altering an intensity of illumination to the other eye to quantify a degree of afferent pupillary defect.

[0197] The applications program(s) can, for example, provide the logic that cause the processor(s) to diagnose health related conditions of a patient or other individual, and, or monitor health or wellness of a patient or other individual which can include identifying sleep related issues, all based on information that represents or otherwise characterizes at least one of physiological eye characteristic(s) (e.g. a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of one or both eyes of a patient, which were detected by one or more of the devices through closed eyelids as generally describedherein. Such can also include identify trends in pupil size, a pupillary light reflex, or an eye position. Such can also include generating alerts or other notifications on occurrence of certain defined conditions (e.g., detection of fixation of the pupil).

[0198] The system may generate an alert, for example, if a change in the pupil size (e.g., as actually measured or a proxy thereof) and / or pupillary reflex and / or eye position of a patient or subject is detected. The system may generate an alert, for example, if a pupil size (e.g., as actually measured or a proxy thereof) has changed by more than a defined threshold (e.g., 1%, 2%, 4%, 5%, 10%). The system may generate an alert, for example, if pupil size (e.g., as actually measured or a proxy thereof) is determined to be more than 3.5 mm, more than 4 mm, more than 4.5 mm in bright light. The system may generate an alert, for example, if a change in pupil size (e.g., as actually measured or a proxy thereof) detected in response to stimulation of the pupillary light reflex is less than a defined threshold (e.g., less than 1%, 2 / %, 5%, 10%.). The system may generate an alert if, for example, a speed of the size of the pupil changes is outside a defined threshold (e.g., 0.5, 1.0, 1.5, 2.0 seconds detected in response to stimulation of the pupillary light reflex). If the system determines that a change in the neurological condition of the patient or subject has occurred, the system may generate an alert.

[0199] The notification can include presenting a determined pupil size, a determined change in pupil size as compared to a reference, or a difference between size or pupillary light reflex response of the pupils of the two eyes of the patient or subject. The notification can include a medical intervention or recommendation to be implemented in response to the determined pupil size, the determined pupillary reflex and / or changes therein. The notifications can include an identification of a neurological status of the patient, as determined based on the pupil size and / or pupillary reflex and / or eye position.

[0200] The detection and, or monitoring can be performed either on-demand or on an on-going basis, either continuously, continually, periodically, or aperiodically (from-time-to-time). Process-executable instructions may include one or more other programs or modules 762, for example to provide for communications with external devices and which may be stored, for example, in RAM 736 during execution. One or more data structures 764 may store information, for example information that identifies specific users, patients or other subjects, values of various vital signs, values of measurements of pupil size (e.g., as actually measured or a proxy thereof), a pupillary light reflex, or an eye position, and / or prognosis or health related outcomes. The data structures 764 may take a variety of forms including databases, data sets, records and fields, tables, linkedlists, trees, binary trees, etc. The data structures 764 may be stored, for example, in RAM 736 during execution.

[0201] In at least some implementations, the device 100 can transmit data off of the device, for example uploading data to an electronic medical record for doctors or clinicians to review. In at least some implementations, the device 100 can transmit data to a server, e.g., a central server or to the “cloud”. For instance, the device 100 can upload anonymous or anonymized data for analysis and development of proprietary software or to be accessed by other companies or researchers to enhance other devices or scientific progress.

[0202] The system memory 732 can store one or more training corpus 765 used in training artificial intelligence systems, artificial neural networks or machine-learning systems. The training corpora 765 includes annotated or unannotated data that that represents or otherwise characterizes the detected at least one of a pupil size (e.g., as actually measured or a proxy thereof), a pupillary light reflex, or an eye position of one or both eyes of a patient, and which is typically associated with information representing associated patient or subject outcomes, and which can be used to train a system to generate a diagnosis or a prognosis, an intervention or set of interventions, and, or, an alert or other notification.

[0203] The system memory 732 can store one or more sets of training instructions 767 that, when executed by at least one processor 730, cause the at least one processor 730 to train an artificial intelligence system, artificial neural network and, or machine-learning system. The training instructions 767 can employ the training corpora 765 in training the artificial intelligence system, artificial neural network or machine-learning system.

[0204] In particular, the system processor-based system 700 can employ deep learning (also known as deep structured learning or hierarchical learning), which is part of a broader family of machine learning methods based on learning data representations using deep neural networks. A deep neural network is an artificial neural network with multiple hidden layers between the input and output layers and can model complex non-linear relationships. Deep neural network architectures generate compositional models where the object is expressed as a layered composition of primitives. The extra layers enable composition of features from lower layers, potentially modeling complex data with fewer units than a similarly performing shallow network. Such can be used to identify conditions generate diagnosis and, or prognosis, based on deep learning to better monitor, assess, and, or treat patients and other subjects based at least in part on data thatrepresents or otherwise characterizes at least one of a pupil size (e.g., as actually measured or a proxy thereof), a pupillary light reflex, or an eye position, of one or both eyes.

[0205] The processor-based system 700 performs a process that ingests the training corpora 765 and trains machine-learning system or artificial neural network using various techniques. The processor-based system learns by using the training corpus 765 or data structure 764 which represents or otherwise characterizes at least one of a proxy for pupil size, pupil size, a pupillary light reflex, or an eye position, of one or both eyes, and also one or more of diagnosis, prognosis, outcomes of various interventions, over a group of patients or subjects. The information may be obtained by the processor-based system 700 through a database (e.g., patient records) and / or through application programming interfaces (APIs).

[0206] The machine-learning system or artificial neural network can generate predictions using Bayesian inference. In such an implementation, the machine-learning system or artificial neural network can generate a data structure that represents the extracted key entities (e.g., values of or changes in proxy for pupil size, pupil size, a pupillary light reflex, or an eye position) and the extracted key relationships of sample training data as a Bayesian network. If Et = {Ei, E2, ... Et} is the history of all events (proxy for pupil size, pupil size, a pupillary light reflex, or an eye position) until time t, the machine-learning system or artificial neural network may use Bayesian inference to predict an event, e.g., occurrence of “low brainstem oxygenation” or “perfusion” or “ischemia” with a probability P(Et+i=“ occurrence of ischemia” | Et), given the history of all events until Et. This may be solved recursively with Bayesian surprise according to P(Et+i | Et) P(Et+i), where P(Et+i) is the prior probability of event Et+i and P(Et+i | Et) is evidence based on previous events in patient or subject history represented across one or more patients or subjects. If the machine-learning system or artificial neural network determines that if P(Et+i | Et) P(Et+i) > T (a threshold), then such an event may warrant generation of an alert of notification.

[0207] The artificial neural network may be trained on the corpus of one or more patient or subject histories. Such can be annotated histories, including information that represents or otherwise characterizes the detected at last one of physiological eye characteristic (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of one or both eyes of a patient or other subjects, outcomes, diagnosis and, or prognosis.

[0208] In some implementations, an artificial neural network can take the form of an auto-encoder that processes information that represents or otherwise characterizes the detected at least one of physiological eye characteristic (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of one or both eyes of a patient or other subjects, outcomes, diagnosis and, or prognosis. The auto-encoder can, for example, be used for learning generative models of data to generate suggested interventions (e.g., next steps), diagnosis and, or prognosis.

[0209] In diagnosis and, or prognosis, the auto-encoder may take the form of a variational auto-encoder, that processes the information with a set of assumptions regarding a distribution of a number of latent (unobserved, inferred) variables. The variational auto-encoder includes an input layer, an output layer and one or more hidden layers connecting the input layer and the output layer. The output layer has the same number of nodes as the input layer and has the purpose of reconstructing its own inputs instead of predicting the target value given the inputs x. This reconstruction is represented by x .

[0210] A variational auto-encoder treats its inputs, hidden representations, and reconstructed outputs as probabilistic random variables within a directed graphical model. In this manner, the encoder portion becomes a variational inference network, mapping observed inputs, represented by x, to (approximate) posterior distributions over latent space, represented by z, and the decoder portion becomes a generative network, capable of mapping arbitrary latent coordinates back to distributions over the original data space. The global encoder and decoder parameters ( / .< ., neural network weights and biases) are represented as and 6, respectively. The mapping of observed inputs to (approximate) posterior distributions over latent space is represented by q<j> (z|x). The sampled z is then passed to the decoder / generative network, which symmetrically builds back out to generate the conditional distribution over input space, represented as reconstruction x ~pe (x|z). The joint distribution of input and latent variables is represented by Pe(x,z) = f P(z) Pe(x\z) and a marginal distribution of input variables is represented by Pe (x) = Pe (x,z)dz. Calculating the marginal distribution (above) is intractable, so the system can use a variational lower bound, represented by log Pe (x) > log Pe (x) - KL(qe (z|x) 11 pe (z|x)), where KL represents the Kullback-Leibler divergence and is a measure of how one probability distribution diverges from a second, expected probability distribution. The KL-divergence is with a variational posterior qe(z\x). The posterior distribution is a normal distribution parameterized by an artificial deep neural network.In someimplementations, an artificial neural network can take the form of a recurrent artificial neural network. The recurrent artificial neural network can be capable of learning longterm dependencies. All recurrent neural networks have the form of a chain of repeating modules of neural network. This repeating module will have a simple structure, such as a single tanh layer. Using such a standard recurrent neural network may often be effective for processing certain information which have a continuous input space. In some implementations, an artificial neural network can include Long Short Term Memory (LSTM) networks, which is a type of recurrent artificial neural network. LSTMs are a kind of recurrent artificial neural network capable of learning long-term dependencies. LSTMs also have a chain like structure, but the repeating module has a different structure than the more basic recurrent neural network blocks. In particular, the LSTM recurrent artificial neural network blocks include a “cell state” which can be analogized to a conveyor belt that runs straight down the entire chain of blocks, with only some minor linear interactions. This allows information to easily flow along it unchanged. Instead of having a single neural network layer, there are multiple layers interacting in a specific way to enable the long-term dependencies. In particular, there can be a sigmoid layer called the “forget gate layer” which decides what information gets discarded from the cell state. This may also be referred to as a “forgetting artificial neural network” that, determines which of the previously generated predictions of the LSTM are reintroduced by the LSTM in the subsequent iterations of predictions. The LSTM block can also include a tanh layer that creates a vector of new candidate values that could be added to the cell state. This may also be referred to as a “generation artificial neural network” that, in one embodiment, generates predictions during a number of iterations of the LSTM.

[0212] In some implementations, an artificial neural network can take the form of a feedforward artificial neural network. A feedforward artificial neural network is an artificial neural network wherein connections between the units do not form a cycle. In the feedforward artificial neural network, the information moves in only one direction, forward, from the input nodes, through the hidden nodes in hidden layers and, to the output nodes. There are no cycles or loops in the feedforward artificial neural network and thus, it is stateless.

[0213] In some implementations, an artificial neural network can take the form of a restricted Boltzmann machine (RBM) that is trained to diagnose health related conditions of a patient or other individual, and, or monitor health or wellness of a patient or other individual which can include identifying sleep related issues, all based on informationthat represents or otherwise characterizes the detected at least one of physiological eye characteristic (e.g., a proxy for pupil size, a pupil size, a pupillary light reflex), and, or an eye position of one or both eyes of a patient, which were detected by one or more of the devices through closed eyelids. An RBM is a generative stochastic artificial neural network that can learn a probability distribution over its set of inputs. In particular, the RBM may model the joint probability of inputs at input layer and outputs at output layer, represented as P(x, y, 6), to generate content. In particular, the artificial deep neural network may be used to determine the probability distribution that gives the probability that each of x and y, representing entities extracted from patient health data, including for example sleep data, falls in any particular range or discrete set of values represented by 6. The artificial deep neural network may also be trained on an annotated data set to extract a number of key entities and a number of key relationships that appear in the patient health data. In particular, the artificial deep neural network may use machine learning wherein the data set used for training may be a set of labeled or annotated records of patient health data used as training examples. The processor-based system 700 may provide functionality for annotating such records of patient health data for training purposes in machine learning.

[0214] The artificial neural network or machine-learning system can, for example, determine a neurological condition of a patient or subject based on a detected physiological eye characteristic (e.g., pupil size or proxy thereof and, or pupillary reflex) and, or detected eye position. The artificial neural network or machine-learning system can, for example, determine a neurological condition of a patient or subject based on a comparison of a size of the pupils of the patient or subject to one another, a comparison of physiological eye characteristic (e.g. a size of the pupil or proxy thereof and, a pupillary light reflex response), and, or eye position to a reference pupil size. The artificial neural network or machine-learning system can, for example, determine a neurological condition of a patient or subject based on a reference pupillary light reflex response, and, or reference eye position, and, or based on a determined trend in the pupil size or proxy thereof and, or pupillary light reflex response, and, or eye position.

[0215] In at least some implementations, a device to detect physiological eye characteristic (e.g., proxy for pupil size, pupil size and / or pupillary reflex) and / or eye position of a patient or other individual or subject includes a first plurality of light emitters operable and positioned and oriented to stimulate or cause an iris light reflex response of an iris through a closed eyelid, a second plurality of light emitters operableand positioned and oriented to transmit light (e.g., infrared light, SWIR light) through the closed eyelid to impinge on and return (e.g., reflect, refracted) from the iris, and a plurality of photodetectors operable and positioned and oriented to detect the light returned (e.g., reflect, refracted) from the iris. The light that stimulates the iris light reflex response is advantageously transmitted from in front of the face and not toward a vitreous cavity of the eye. Thus, a device for physiological eye characteristic (e.g., pupil size or proxy thereof, and / or pupillary reflex) assessment in a subject having closed eyelids, the device including one or more light sources that transmit light through a closed eyelid and detects light returned through the closed eyelid.

[0216] Physiological eye characteristic(s) (e.g., pupil size or proxy thereof, or pupillary light reflex) may be evaluated at the time of an emergency response. Physiological eye character! stic(s) (e.g., pupil size or proxy thereof, and, or pupillary light reflex) may be evaluated at the time of a hospitalization. Physiological eye characteristic(s) (e.g., pupil size proxy thereof, and, or pupillary light reflex) may be evaluated at the time of a clinical visit. Physiological eye character! stic(s) (e.g., pupil size or proxy thereof, and, or pupillary light reflex) may be evaluated just prior to or during a surgery. Physiological eye character! stic(s) (e.g., pupil size or proxy thereof, and, or pupillary light reflex) may be evaluated in a non-responsive patient (e.g., sedated, passed out, comatose).Physiological eye characteristic(s) (e.g., (e.g., pupil size or proxy thereof, and, or pupillary light reflex) may be evaluated in a responsive patient.

[0217] In some implementations, the device may detect a size of the pupil size or a proxy thereof without triggering, detecting or quantifying pupillary light reflex, (i.e., not emitting reflex trigger light in the 520nm-650nm range), and only the second plurality of light sources are activated.

[0218] In some implementations, the second plurality of light sources emit light in the infrared (IR) range, for instance in the near IR (NIR) range (e.g., 800 nm-1 mm) or shortwave infrared (SWIR) range (e.g., 900 nm-2500 nm). The second plurality of light sources can emit light as part of detecting or otherwise measuring of a size of the pupil (i.e., pupil size) or a proxy thereof, for instance before inducing a pupillary light reflex response.

[0219] The photodetectors can be sensitive or responsive to light in the IR range, for instance the near IR range. The device may optionally include an optical long pass filter (e.g. 800 nm) to reduce background light.

[0220] The number and positions of photodetectors that detect returned (e.g., reflected, refracted) light can provide an indication of a contour and, or a shape of an inner perimeter of the iris and hence of an outer perimeter of the pupil. Thus, a size (e.g., diameter) of the pupil can be determined, as well as a response (e.g., change in size) can be determined based on detections at successive intervals of time. Alternatively, a measure of an amount of light detected can serve as a proxy for pupil size.

[0221] In some implementations, the first plurality of light sources emit light having a wavelength (e.g., 400 nm-1000 nm, or 400 nm-700 nm) and, or, an intensity that induces a pupillary light reflex, which can be used to detect or measure a change in a size of a pupil (i.e., pupil size or proxy thereof) in response to the light and, or a speed of change in a size of a pupil in response to the light i.e., individually or collectively pupillary light reflex response). A change in the size of the pupil or proxy thereof and, or pupillary light reflex response is detected or measured and compared either to reference pupil size or reference proxy thereof, for instance an average size of pupil or average measure of light returned across a population (e.g., population with normal pupil size and, or normal pupillary light reflex; population of specific gender and, or specific age, population with specific underlying health issues or risks) or to a size of pupil or amount of light returned and, or pupillary light reflex response initially detected or measured on initial patient intake, or detected or measured a some other instance of time for the patient or subject. The detected or measured size or amount of light detected and, or pupillary light reflex response detected when a patient or subject is asleep can be compared to that of when the patient or subject is awake. The detected or measured size of the pupil or proxy thereof and, or, pupillary light reflex response for one eye can in some instances be compared to that of the other eye (i.e., comparison between eyes). Pupil size or proxy thereof and / or pupillary light reflex reaction may be detected individually for each eye, or simultaneously for each eye, and can be detected sequentially for any given eye.Detecting different pupil sizes or amounts of light detected between the two eyes (i.e., anisocoria) of an individual or a difference in speed of change of the pupil size between two eyes of the individual or a different in the amount of light returned from two eyes may indicate increased intracranial pressure, concussion or other head trauma, ischemia, Alzheimers, Parkinsons, diabetes, heart disease, pain, opiate level, anesthetic level, cardiac perfusion of the brain, sleep stages, or other conditions.

[0222] The device can include a processor (e.g., microcontroller) that controls operation of the first and the second plurality of light emitters. The processor can also determine asize of the pupil based on a number and relative location of light sensors (e.g., photodetectors) that detect or do not detect light returned from the iris via the closed eyelid by the light sensors (e.g., photodetectors). The processor can use a number and relative location of light sensors (e.g., photodetectors) that detect or do not detect light returned from the iris via the closed eyelid as a proxy of pupil size. The processor can, in some implementations, determine a contour and / or shape of an inner periphery of the iris and hence the outer periphery of the pupil based on which light sensors (e.g., photodetectors) detected at least a threshold level of light returned from the iris.Alternatively, the processor can rely on a proxy of pupil size, for example an amount of light returned that is detected by the light sensors (e.g., photodetectors). The processor can also determine a trend in the detected or measured size of the pupil or proxy thereof, and, or pupillary light reflex response over time, for example representing a change in the size of the pupil or proxy thereof, or a change in the pupillary light response over time. Using a trend may allow better detection of incremental but significant changes in the proxy of pupil size, pupil size and / or pupillary light reflex response which can be indicative of a neurological issue.

[0223] The processor can generate or produce and alert or a notification if certain thresholds are met, or if an acute condition is identified.

[0224] In at least one implementation, a method includes: operating the second plurality of transmitters to transmit light of a second range of wavelengths through the closed eyelid to be returned by the iris; detecting the light returned from the iris by a plurality of light sensors (e.g. , photodetectors), and determining a size of the pupil or proxy thereof based a position of the light sensors (e.g., photodetectors) that detect on the light returned from the iris or based on an amount of returned light detected.

[0225] In at least one implementation, a method includes: operating the first plurality of transmitters to transmit light of a first range of wavelengths through a closed eyelid, to cause a pupillary light reflex response, operating the second plurality of transmitters to transmit light of a second range of wavelengths through the closed eyelid to be returned by the iris; detecting the light returned from the iris by a plurality of light sensors (e.g., photodetectors), and determining a pupillary light reflex response based on a position of the light sensors (e.g., photodetectors) that detect on the light returned from the iris.

[0226] In at least one implementation, a method further includes: comparing a determined size of the pupil or proxy thereof, and, or determined the pupillary light reflexresponse to a reference size of the pupil or reference proxy thereof, and, or a reference determined the pupillary light reflex response.

[0227] In at least one implementation, a method further includes: comparing a determined size of the pupil or proxy thereof, and, or a determined the pupillary light reflex response for a patient or subject that was determined at a first time to a determined size of the pupil or proxy thereof, and, or a determined the pupillary light reflex response for the eye of the patient or subject that was determined at a second time, the second time different from the first time.

[0228] In at least one implementation, a method further includes: comparing a determined size of the pupil or proxy thereof, and, or determined the pupillary light reflex response for a first eye of a patient or subject to a determined size of the pupil or proxy thereof (e.g., amount of returned light), and, or determined the pupillary light reflex response for a second eye of the patient or subject.

[0229] In at least one implementation, a method further includes: monitoring a condition of a patient or other subject based on at least one of the determine size of the pupil or proxy thereof, and, or determined the pupillary light reflex response.

[0230] In at least one implementation, a method further includes: monitoring a condition of an unconscious patient or other subject based on at least one of the determine size of the pupil or proxy thereof, and, or determined the pupillary light reflex response.

[0231] In at least one implementation, a method further includes: monitoring a sleep state condition of a patient or other subject based on at least one of the determined size of the pupil or proxy thereof, and, or determined the pupillary light reflex response.

[0232] In at least one implementation, a method further includes: submitting at least one of a determined pupil size, proxy thereof (e.g., amount of returned light), a determined pupillary light reflex, or a determined eye position of an eye to a trained artificial neural network or a machine-learning system to assess a health condition of a patient or other subject based on at least one of the determined size of the pupil, proxy thereof, and, or determined the pupillary light reflex response.

[0233] In at least one implementation, a method further includes: determining if an abnormal condition exists in at least one of pupil size or proxy thereof, and, or pupillary light reflex response; and in response generating an alert or other notification.

[0234] In at least one implementation, a method further includes: detecting the eye position of the eye; and selectively controlling which of the light emitters of the first plurality of light emitters is active based at least in part on the eye position of the eye tosteer the light emitted by the light emitters of the first plurality of light emitters. Since it is not known a priori which way an eye will be pointing, the device can detect and, or track eye position. Hence, the light emitted by the light emitters of the first plurality of light emitters is steerable. The device can then steer the emission of the light emitters of the first plurality of light emitters (e.g., white light source) in real-time based on eye position and a feedback loop, for example by activating selected ones of the light emitters of the first plurality of light emitters where the respective principal axes of omission of the light emitters of the first plurality of light emitters are generally non-parallel to one another oriented given the conformance of the substrate and device to the portion of the eye. This approach can advantageously allow the light emitters of the first plurality of light emitters to be spread out more diffusely on the substrate. For example, the light emitters of the first plurality of light emitters are dispersed across the central region and the peripheral region of the substrate. Such advantageously provides for increased pliability and, or compliance and, or conformability of the substrate.

[0235] In at least one implementation, a method includes: directing diffuse illumination toward the eye from the light emitters of the first plurality of light emitters to activate the retina, for example via an extra-pupillary pathway. Diffuse illumination can be emitted by the light emitters of the first plurality of light emitters, or the light emitted by the light emitters of the first plurality of light emitters may be diffused via an optical component (e.g., optical diffuser) positioned along an optical path that extends from the light emitters of the first plurality of light emitters outward from the device 100 toward the eye, for example outward from an eyelid contacting surface that in use contacts, and may even be adhered to, the outer surface of the eyelid. Thus use of diffuse light (e.g. a diffuser) can advantageously reduce or eliminate the use of eye tracking to orient the emission of light described herein.

[0236] The device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B) can be fabricated using a conventional circuit assembly process using a high temperature flexible substrate such as polyimide. This can be fabricated using a flexible circuit assembly process using, for example, a patterned, laminated copper foil, together with a patterned solder mask and assembled LEDs, photodetectors, and support electronics.

[0237] The LEDs used are structured with or without a reflector and / or other optics to project the light along a principal optical axis at a shallow angle, allowing for a scattering off of the iris. In one implementation, each infrared LED is turned on in sequence, and the photodetector signal is measured, followed by the next LED and each light sensor(e.g., photodetector) and so on, permitting a measurement of each combination of LED and light sensors (e.g., photodetector). This correlation can then be used to map the optical paths that include the iris (which reflects / refracts / scatters light) and differentiate them from the paths that include the pupil (which is not reflective). The LEDs may advantageously take the form of micro-LEDs.

[0238] Machine learning and more sophisticated analytical techniques can be used to determine the position of the eye and the size of the pupil or proxy thereof (e.g., amount of light returned). In another implementation, multiple LEDs can be turned ON in a determined pattern and the correlation used for the analysis. In another implementation, a subset of the LEDs and light sensors (e.g., photodetectors) can be used, based on the sensitivity to the position and pupil. Such an optimization can improve, for example, the cost of the system by reducing the number of elements, or improve the signal to noise ratio by allowing for a larger detection duty cycle or a faster measurement period with fewer elements in the sampling period.

[0239] An additional benefit of a periodic signal is that synchronous detection and correlated sampling can be used, in which the signal is analyzed at the stimulation frequency of the LED, permitting a reduction in the detector noise and cancellation of the system dark current and background photodetection (e.g. due to ambient light). The signal received by the light sensors (e.g., photodetectors) is, in this way, correlated with the LED which is activated at each measurement period and used to determine the light scattered and reflected, or refracted or otherwise returned from the eye.

[0240] The device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B) can be configured as a wireless system, in which there is a power management circuit and battery, and wireless communication (e.g. via Bluetooth or other radio signals) is used to communicate.

[0241] The device 100 (Figures 1A-1C), 300a (Figure 3A), 300b (Figure 3B) can alternatively be configured as a tethered system with both power and the data signal transmitted over a wire.

[0242] Data analysis can be performed either on the device 100 (Figures 1 A-1C), 300a (Figure 3A), 300b (Figure 3B), or can be performed remotely following signal communication. Data reduction can occur on the device, advantageously reducing the volume of data that is communicated. Alternatively, transmitting the raw data can simplify the electronics used on the system and reduce the power consumption of the sensor.

[0243] The plurality of light sensors 108 can operate continuously or be activated on a fixed schedule or using signals from other sensors being used to monitor the patient. A processor can, for example, samples the plurality of light sensors 108 at a defined delay time after activation of the light emitters of the first plurality of light emitters. The sensor information and schedule of measurement or detection can further be determined by information from other types of sensors (e.g., mechanical sensors that can detect REM of the eyes under the eyelid).

[0244] The system can assess eye position (e.g., gaze direction, eye movements), in addition to proxy of pupil size, pupil size, and the pupillary light reflex response, all of which are useful in neurological examination and constitute a useful tool a wide variety of clinical settings. Such can be used in critical care through sleep studies. In particular, short-wave infrared (SWIR) light can be directed to the iris through a closed eyelid and returned from the iris through the eyelid to detected eye position, along with performing pupillometry. The system can alternatively or additionally employ one or more mechanical sensors e.g., piezo-electric transducers, or ultrasound transducers and systems) to detect eye position or eye movement.

[0245] The system can monitor or test a subject using physiological eye characteristic (e.g., proxy of pupil size, pupil size, pupillary light reflex response) and, or eye position to detect onset of a variety of diseases, for example: concussion and mild traumatic brain injury, Alzheimer's Disease and Parkinson's Disease, heart disease, diabetes, cardiac arrest, level of brain perfusion, and ophthalmological diseases such as cataracts, retinitis pigmentosa, amblyopia, macular degeneration, and glaucoma, Such can also identify or diagnose concussion, for example via detection for both eyes (e.g., via a mask). Such can also predict a return to baseline as well as help in the early detection of diseases that effect the autonomic nervous system (e.g., Alzheimer's and Parkinson's).Monitoring Sleep

[0246] Adequate sleep is crucial for mental and physical health. Sleep disorders impact almost 70% of the population, contributing to the progression of heart disease, obesity, diabetes, and decreasing worker productivity, which results in an enormous economic burden. On-call professions, such as physicians, pilots, soldiers and truck drivers, may suffer from sleep inertia when aroused in the middle of the night, a grogginess that can last up to 30 minutes that impairs the performance of physical and mental activities.

[0247] Sleep is divided into four stages: light (Nl, N2) sleep and deep (N3) and REM (rapid-eye movement) sleep. Critical to the ability to diagnose and treat sleep disorders isthe ability to accurately measure sleep stages. The current gold standard is polysomnography (PSG), an in-hospital test that relies on electroencephalography (EEG) and electrooculography (EOG). This test is expensive, uncomfortable, labor-intensive, and suffers low inter-rater reliability. The industry is moving to in-home testing but these studies, as well as the more popular health tech wellness devices, generally do not include EEG and EOG. Instead, they rely on heart rate, heart rate variability, movement, temperature and oxygenation to approximate sleep stages, which significantly lowers their accuracy. There is a desperate need for a low-cost, comfortable device that can accurately measure sleep stages outside a hospital setting.

[0248] The size of the pupil is controlled by the autonomic nervous system and directly correlates with level of arousal, cortical synchronization, and locus coeruleus noradrenergic activation. During sleep, the pupil constricts and dilates depending on the depth of sleep and the level of arousal, in direct correlation with sleep stages. Larger pupil sizes indicate lighter sleep and higher levels of arousal and pupil size tracks closely with sleep stages between Nl, N2 and N3-N4. Combined with eye movement monitoring to separate N3 from REM, all four sleep stages could be measured accurately using pupillometry. The pupil is also a sensitive measure of sleep microarchitecture including sleep spindles, K-complexes, and arousals.

[0249] Sleep is also important for memory consolidation. A recent study in mice has shown that the size of the pupil during sleep correlates with recent memory consolidation as well as replay of older memories. A sleep mask that tracks pupil size or a proxy thereof could be employed as a method for measuring adequacy and amount of memory consolidation during sleep.

[0250] Light is a powerful neurostimulant that exerts its alerting effect on the human brain through intrinsically photosensitive retinal ganglion cells that synapse on the suprachiasmatic nucleus of the hypothalamus. Their peak activation is 480nm, which also maximally suppresses the secretion of melatonin, the body’s pro-somnolent hormone. Exposure to short-wavelength light has been shown to increase alertness, reduce EEG delta-theta power, a biomarker of sleepiness, and increase alpha and high-alpha power, a biomarker of alertness. Likewise, continuous long- wavelength (red) light therapy during sleep has been shown to reduce sleep inertia. Moreover, 40 Hz light stimulation during sleep can entrain brain oscillations and improve glymphatic drainage to enhance sleep quality. 40Hz stimulation during wakening can increase alertness to overcome sleep deprivation. The effect occurs both during nighttime as well as morning awakenings.Although most studies employ light at durations of minutes, repeated brief pulsations as short as 2 ms are also effective at altering circadian rhythms and increasing alertness. In several studies, 40 Hz light stimulation has been shown to entrain 40 Hz brain oscillations and increase memory consolidation and alertness with potentially therapeutic effects on diseases such as dementia or Alzheimer’s.

[0251] One implementation of the device described herein embodies a sleep mask that will non-invasively and continuously track the size of the pupil or a proxy thereof (e.g., amount of light returned from the eye through the closed eyelid) during sleep to measure alertness level, sleep stages, (including macro- and micro-architecture) eye position as well as eye movement and blink frequency to identify REM sleep. This smart sleep mask can also measure recent memory consolidation based on pupil size analysis or analysis of a proxy of pupil size. Light stimulation during certain sleep stages can be employed to enhance sleep or brain function including green light therapy to treat diabetic retinopathy and other retinal diseases, blue light therapy to entrain circadian rhythms, red light therapy to increase alertness, high frequency stimulation (e.g. 40Hz) to enhance cognition. Light therapy during sleep can be used to treat psychiatric illnesses such as anxiety, depression, schizophrenia, bipolar disorder, mood disorders, obsessive compulsive disorder, among others. Finally, a closed-loop analysis algorithm which can include artificial intelligence (Al) or artificial learning (AL) or machine learning (ML) will permit the user to set a time window during which illumination with short- medium-or long- wavelength light will adaptively awaken the user during a period of high arousal to minimize sleep inertia, or impact the sleep stages in some way to regulate sleep for better sleep, more restful sleep, less sleep inertia, improved REM, or improved alertness, focus or memory consolidation.

[0252] The system can monitor a subject, using pupil size or proxy thereof to identify various sleep stages and arousals, for example during a sleep study of a patient. It is noted that pupil size is correlated with sleep stages and arousals. Memory formation and memory consolidation often occurs during certain stages of sleep. It is noted that the pupil not only gets smaller during human sleep but exhibits fluctuations in size called pupillary waves. Thus, pupil size or proxy thereof can be used as a measure of short-term memory consolidation during non-REM sleep. The system can monitor or test a subject to quantify a measure of new memory formation and memory consolidation. The devices can be incorporated into a mask e.g., a sleep mask), allowing quantification of how successfully a subject is able to make new memories from what they experienced that day. The systemcan generate a "memory scale" to quantify how successfully a given night's sleep contributed to forming memories.Monitoring vision in the Operating Room (Chromatic Pupillometry and Red Reflex IP)

[0253] Accidental vision loss is a devastating complication that can occur during several different types of operations, including cardiac, spine, brain, sinus, and carotid artery surgery. Surgeons generally rely on intraoperative monitoring to provide feedback for early warning of damage to important at-risk physiological functions so they can alter their behavior to avoid iatrogenic injury. Applicant is not aware of any highly reliable autonomous method for monitoring vision in an anesthetized patient in an operating room. Visual-evoked potentials are cumbersome, unreliable, and not sufficiently sensitive to visual deterioration. The pupillary light reflex is an alternative method for assessing the functional integrity of the anterior components of the visual pathway, which includes the exterior and interior retinal cells, the optic nerve, the brainstem, and the oculomotor nerve. Loss of the pupillary reflex highly correlates with degree of retinal ischemia, mechanical injury, brainstem ischemia, and reduction in visual acuity and visual fields, making it an excellent method for probing the integrity of the anterior visual pathways.

[0254] Chromatic pupillography is a more sophisticated test that relies on different light sensitivities and kinetics of the various retinal cells — rods, cones and intrinsically photosensitive retinal ganglion cells (ipRGCs) — to probe the retinal cells individually. The ipRGCs, in particular, appear to be more sensitive to retinal ischemia and mechanical trauma. Their slower kinetics and a delayed post-illumination pupillary response (PIPR) after sustained blue light offset, allow the ipRGCs to be examined separately from the rods and cones using specific illumination parameters, which may provide the earliest possible signs of injury. Chromatic pupillometry has been used to diagnose several different ophthalmologic conditions such as glaucoma, retinitis pigmentosa, seasonal affective disorder, anterior ischemic optic neuropathy, macular degeneration, cataracts, lazy eye, Alzheimer's Disease, Parkinsons’ s Disease, heart disease, diabetes, multiple sclerosis, concussion, among others.

[0255] The red reflex, or Bruckner effect, describes a phenomenon where visible light (e.g., white light) passing through an enlarged pupil returns out the pupil with a preferential reflection of the red light over shorter wavelengths.. This effect is often noticed when using flash photography. Alterations in the red reflex can be used in clinicalmedicine to diagnose diseases such as retinoblastoma, amblyopia, cataracts or refractive errors.

[0256] In at least one implementation of the device described herein an eye patch (e.g., adhesive eye patch), sleep mask or goggles, continuously or intermittently performs both or either of white light, single wavelength, and chromatic pupillometry, including measurement of the PIPR, through a closed eyelid. This includes measurements of alternating blue (460-490 nm) and red light (610-645 nm) at durations ranging from 0.1 ms to 10 s. Another implementation of the device described herein measures the red reflex, either to aid in measuring the pupil size or a proxy thereof to compare one eye with the other eye to diagnose alterations in the red reflex associated with disease states.

[0257] Various implementations of the device described herein can be used to diagnose a variety of ophthalmologic conditions, such as glaucoma, retinitis pigmentosa, retinoblastoma, amblyopia, seasonal affective disorder, anterior ischemic optic neuropathy, macular degeneration, cataracts, lazy eye, Alzheimer's Disease, Parkinsons’ s Disease, heart disease, diabetes, multiple sclerosis, concussion, marijuana use, spaceflight neuro-ocular syndrome, or any disease effecting the autonomic nervous system, as well as visual loss from retinal ischemia or mechanical trauma during surgery. The device can also be employed to provide feedback during cardiac resuscitation to determine if the efficacy of the resuscitation based on the pupillary response. The device can be used after cardiac arrest, for instance in an ICU patient to predict recovery.Monitoring Pain and Opioid Concentration in the Operating Room

[0258] The size of the pupil and the pupillary light reflex also provide information on depth of anesthesia and pain. With deeper levels of anesthesia, particularly inhalational anesthetics, the pupil becomes progressively smaller. However, the pupil still responds to light. Several studies have demonstrated that the size of the pupil and the pupillary light reflex can be used to monitor depth of anesthesia and helpful in the titration of a variety of anesthetics. The pupil also enlarges in response to painful stimuli due to the sympathetic pain reflex. The pupil can be employed during operative procedures to monitor the patient’s level of pain, even if the patient is sedated and provide feedback to anesthesiologists to allow the anesthesiologist to titrate anesthetics and narcotics.Likewise, the size of the pupil is a sensitive measure of narcotic dose and narcotic toxicity. The size of the pupil decreases with increasing concentrations of narcotics. Even at high narcotic concentrations, the pupillary light reflex remains functional, even with small pupil sizes. Anesthesiologists, or even the system itself, can use the size of the pupilor a proxy thereof, and, or the pupillary light reflex to monitor narcotic concentration during surgery to ensure that adequate levels are given and that overdosages do not occur. For instance, alerts may be presented at defined threshold values for various pupil sizes or proxies thereof, and, or various values representative of the pupillary light reflex.

[0259] In at least one implementation, the device described herein allows an anesthesiologist to monitor pain, depth of anesthesia and narcotic concentration in real time during an operation, allowing them to adjust their administration of anesthesia and narcotics to ensure adequate pain control and reduce the incidence of narcotic overdosages, thereby facilitating rapid wake up after surgery. This includes monitoring pain in response to an administered painful stimulus such as corneal, trigeminal nerve, irritation or noxious stimulation of an extremity by mechanical, electrical or chemical means. This will ensure rapid awakenings after surgery and more rapid turn-over in the OR and post-anesthesia recovery rooms, decreasing length of stay and reducing rates of opioid addiction. In some instances, the device itself can monitor pain, depth of anesthesia and narcotic concentration in real time during an operation, and can present alerts at defined threshold values for various pupil sizes or proxies thereof, and, or for various values representative of the pupillary light reflex to prompt the anesthesiologist to adjust their administration of anesthesia and narcotics to ensure adequate pain control and reduce the incidence of narcotic overdosages. In yet other implementations, the device itself can monitor pain, depth of anesthesia and narcotic concentration in real time during an operation, and can control delivery of administration of anesthesia and narcotics based on defined threshold values for various pupil sizes or proxies thereof, and, or for various values representative of the pupillary light reflex to ensure adequate pain control and reduce the incidence of narcotic overdosages.Monitoring cranial nerve function

[0260] During operations around the cranial nerves, surgeons often perform intraoperative monitoring of motor function of various cranial nerves. This usually involves intraoperative stimulation of a cranial nerve, such as the third nerve, fourth nerve or sixth nerve that moves the eye and the seventh nerve that moves the facial musculature. The muscles are then monitored with needle electrodes placed into the effector muscles that the nerves are activating. If responses diminish, then the surgeon knows that the nerve’s ability to transmit electrical information has been compromised.

[0261] One version of this device allows a surgeon or neurophysiologist to monitor the muscles that move the eye or cause blinking with the optical eye-patch or sleep mask.Continuous monitoring of eye position, movement and blinking will provide real time feedback to the surgeons of the functioning of the third, fourth, sixth and seventh cranial nerves, while they are operating and while they are stimulating the nerves with electrode.Eyelid Physiology Measurement and Feedback

[0262] Light transmission through the skin is determined by the optical properties of the skin, including the absorption and scattering coefficients of the skin at given wavelengths. Understanding the optical properties of skin is useful for the development of light-based diagnostic medical technologies and to avoid pigment-based inaccuracies. Light transmission can be calculated based on the intensity of light reaching a certain depth, into a medium with a defined scattering and absorption coefficients. There are four key absorbing elements in the eyelid: 1) deoxy- and oxy-hemoglobin, 2) melanin, 3) bilirubin, and 4) the non-absorbing, scattering macromolecules.

[0263] Light transmission through eyelids has strong wavelength dependence. For example, light at 700nm transmits up 100X more than at 450nm and light at 970nm transmits 1200X more than light at 530nm. Although melanin and pigment impair light transmission, the largest losses of light occur from scatter due to nonpigmented constituents of the eyelid, such as dense connective tissue, macromolecules, keratinocytes, collagen, and fat, which all contribute to skin thickness. The thickest part of the upper eyelid is just below the eyebrow (l.l±0.2 mm), and the thinnest part near the ciliary (eyelash) margin (0.3 ±0.05 mm), where the Meibomian glands transmit very little light. The ability of the device described herein to measure the size of the pupil and the direction of gaze may be influenced by individual variations in light transmittance properties of the eyelid.

[0264] There are various approaches which the system can use to measure light transmission, absorption, reflection and eyelid thickness including spectrometry and high-resolution ultrasound biomicroscopy, including B-mode. These techniques can measured beforehand, or built into the device, to adjust the light intensity or other parameters of the device to improve functionality.

[0265] At least one implementation of the device described herein includes the structures and executable instructions to adjust a wavelength of intensity of light to compensate for individual variations in eyelid thickness, pigmentation and light transmission. Measurements can be made with a separate spectrometer, ultrasound or even the amplitude of the pupillary light reflex itself at a known wavelength and light intensity prior to employing the device 100. In another embodiment, the device 100includes an embedded spectrometer and, or an embedded ultrasound transducer and / or system which measures or otherwise determines eyelid physiological parameters and autonomously adjusts the wavelength or light intensity of emitted light based on real-time readings.

[0266] The processor of the device 100 can automatically or autonomously adjust an amount of light emitted (e.g., adjust intensity) based on the measured or otherwise determined eyelid physiological parameters. For example, the processor can adjust the number of light emitters that are activated and, or adjust an amount of power of emission of the light emitters based on the measured or otherwise determined eyelid physiological parameters, for instance by adjusting an amount of power supplied to the light emitters. Additionally or alternatively, the processor of the device 100 can automatically or autonomously adjust the light sensors based on the measured or otherwise determined eyelid physiological parameters. For example, the processor can adjust the number of light sensors that are active or a sensitivity of the light sensors. Additionally or alternatively, the processor can adjust values representative of light sensed or detected by the light sensors to normalize those values based at least in part on based on the measured or otherwise determined eyelid physiological parameters.Calibration

[0267] The processor of the device 100 can automatically or autonomously perform calibration, for example assesses an output of the light emitters and, or the sensitivity of the light sensors, from time-to-time. For example, the processors can cause one, more or all of the light emitters of the first or the second plurality of light emitters to emit light sequentially or concurrently. The processor uses a measure of the returned light as sensed by the light sensors to determine whether the light emitters are emitting light at a defined intensity. The light may, for instance, be returned from a target (e.g., white target) with a known or otherwise constant reflective value. Alternatively, the light may, for example be returned the sclera or other portion of the eye with the eyelid open. Such can be performed for an entire wavelength range of the light emitters or for selected wavelengths of the light emitters. The processor can then adjust the number of active light emitters, adjust a mix of active light emitters where the light emitters of a given plurality of light emitters include two or more types of light emitter, each type operable to emit light at a respective intensity or power level, and, or adjust a power output of the light emitter(s) (e.g., via control of power supplied (e.g., power setting) to the light emitter(s)) to reach a defined desired intensity. Alternatively or additionally the processor can adjust asensitivity of the light sensor(s) or otherwise adjust a signal representative of the light measured or detected by the light sensor(s) in response to either a change of light emission from the light emitter(s) from a nominal value or a change of light sensitivity of the light sensor(s) from a nominal value.

[0268] The device may advantageously employ calibration. For example, the device can be placed over one eye while simultaneously opening the contralateral eye, the device and measuring a size of the pupil and then inducing and measuring the pupillary light reflex. In this way, the device can calibrate the signals from the device recording over the closed eye, with a ground truth measurements of the actual pupil size and reflex in the open eye. The calibration device placed over the open eye would use a standard white light and an infrared sensor (e.g. , IR-responsive camera) to measure the pupil size and induce the reflex. This might be done each time the device is placed on the eyes or prior to each use.Other indications

[0269] At least one implementation of the device described herein, the processor determines or measures refractive errors. At least one implementation of the device described herein the processor determines or measures retinal blood flow and oxygenation comparing the absorption and reflection of light in the retina, based on hemoglobin oxygenation using more than one wavelength of light including isosbestic and non-isosbestic wavelengths and calculations such as Beer-Lambert transformations. At least one implementation of the device described herein, the processor determines or measures intraocular pressure using the echo of ultrasound waves as a proxy for pressure. At least one implementation of the device described herein the processor determines or performs optical coherence tomography (OCT). At least one implementation of the device described herein, the processor controls the light emitters to diagnose changes in lens refraction based on relative pathlength comparisons of light passing through the lens from different sources. At least one implementation of the device described herein, the processor controls the light emitters to treat retinal disease with green light therapy.

[0270] The device 100 (Figures 1A-1C), 300a (Figure 3A), 300b (Figure 3B) can execute an algorithm.

[0271] For example, the processor 602 (Figures 6A-6C) of the device can initially activate the light emitters of the second set of light emitters to emit light through the closed eyelid(s).

[0272] The light sensors (e.g. , photodetectors) then detect light returned from the pupil through the closed eyelid(s). The processor 602 samples an output of the light sensors(e.g., photodetectors) to determine which light sensors (e.g., photodetectors) detected light and, or a level or an intensity of the light detected by each light sensors (e.g., photodetector) or a total amount of light detected.

[0273] The processor 602 then determines an eye position e.g., position and, or orientation of the iris and, or the pupil) based on which light sensors e.g., photodetectors) then detect light returned from the pupil and, or based on a level or an intensity of the light detected.

[0274] The processor 602 then determines how to steer the light emission of the first plurality of light emitters. For example, the processor 602 determines a target orientation of a principal axis of emission based on the determined eye position. The processor 602 then determines which of the light emitters of the first plurality of light emitters to activate (i.e., turn ON or otherwise cause to emit light) in order to achieve the target orientation of the principal axis of emission which is based on the determined eye position the eye. The processor 602 then activates the determined light emitters of the first plurality of light emitters to emit light in order to achieve the target orientation of the principal axis of emission of the first plurality of light emitter collectively.

[0275] The processor 602 can then optionally wait a defined delay time after activation of the light emitters of the first plurality of light emitters, allowing the iris to react and the pupil to dilate.

[0276] The processor 602 can then activate the light emitters of the second set of light emitters (e.g., for a second time) to emit light through the closed eyelid(s).

[0277] The light sensors (e.g. , photodetectors) then detect light returned from the pupil through the closed eyelid(s). The processor 602 samples an output of the light sensors (e.g., photodetectors) to determine which photodetectors detected light and, or a level or an intensity of the light detected by each light sensors (e.g., photodetector), or a total amount of light detected.

[0278] The processor 602 can then determine at least one of a pupil size or a proxy thereof (e.g., amount of light returned), and, or a pupillary light reflex based on which light sensors (e.g., photodetectors) detected light and, or a level or an intensity of the light detected by each light sensor (e.g., photodetector), or a total amount of light detected.

[0279] The above acts can be repeated continuously, continually, periodically, aperiodically, or on demand.

[0280] The processor 602 can optionally transmit information that represents the determined at least one of a pupil size, proxy thereof, and, or a pupillary light reflex to a processor-based system, for instance via a wired or wireless interface.

[0281] The processor-based system can use information that represents the determined at least one of a pupil size, proxy thereof, and, or a pupillary light reflex to assess, diagnosis, and, or monitor a condition of a patient or subject. The processor-based system can use one or more artificial neural networks or trained machine-learning systems in assessing, diagnosing, and, or monitoring a condition of a patient or subject. The processor-based system can produce alerts and, or notifications indicative of the pupil size and, or a pupillary light reflex, an assessment, diagnosis, and, or condition of a patient or subject.

[0282] Figure 8 show a high-level method 800 of operation of a device 100 to detect at least one of physiological characteristic(s) (e.g., proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation.

[0283] At 802, the device 100 starts operation, for example in response to a power ON event. In some implementations, the device 100 can be powered by a battery, and removal of a release liner can complete a circuit between the battery and the circuitry of the device causing the device to power ON and start the method 800. In other implementations, the device 100 can include a switch, operable to start operation.

[0284] At 804, the device optionally performs a calibration routine. Such can include calibrating the light emitters of the first plurality of light emitters, calibrating the emitters of the second plurality of light emitters, and, or calibrating the light sensors. As described above, a calibration target can be employed, for example a calibration target having a known or at least a constant reflectivity. Alternatively, the sclera of the eye can be employed as a calibration target. The calibration can ensure that light emitters emit at a defined intensity level and, or that the light sensors are operating at a defined sensitivity. The calibration can adjust the output of the light emitters to accommodate for difference from nominal values of emission intensity. Additionally or alternatively, the calibration can adjust a sensitivity of the light sensors to accommodate for difference from nominal sensitivity values, or alternatively can adjust values output by the light sensors accordingly to accommodate for difference from nominal sensitivity values.

[0285] At 806, the device 100 optionally detects eye position. The device 100 can employ any of a variety of structures and method to detect eye position. For example, the device can detect reflections (glint) returned from a portion of the eye, or can employultrasound or a mechanical sensor or transducer (e.g., piezo-electric crystal) to detect and, or track eye position.

[0286] At 808, the device 100 detects eye physiological characteristic(s) which are related to, and, or which represent pupil size and / or pupillary reflex(s). Examples of such detection are described herein. For instance, an amount of light returned from the eye via the closed eyelid can be a proxy for pupil size, and can either be converted to a measure of pupil size or can be used directly as a proxy thereof. Also for instance, which light sensor detect light returned from the eye via the closed eyelid can be a proxy for pupil size and can either be converted to a measure of pupil size or can be used directly as a proxy thereof. For instance, the position and relative spacing of light sensors that detect light returned from the eye can correspond or be correlated to a size of the pupil. Notably, light returned and detected by light sensors represents light that has not passed through the pupil, so can provide an outline of the outer contour of the pupil. Using the amount of light returned or using an identity, position or spacing of the light sensors that detect returned light can both advantageously avoid costly and complicated imaging processing used by conventional approaches. Such can also advantageously be realized with many fewer light sensors (e.g., 6, 12 or 20 light sensors) than used in digital cameras e.g., video cameras, 45 megapixel sensors) employed in conventional approaches.

[0287] At 810, the device 100 optionally determine pupillary reflex value(s) based on successive detected eye physiological characteristic(s). The device 100 can use detections of the amount of light or a knowledge of which the light sensors detected light at successive instances of time to determine a change in a proxy of pupil size, pupil size or change in proxies of pupil size. The device 100 can, for example, determine one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline.

[0288] At 812, the device 100 assess a condition based on eye physiological characteristic(s), pupillary reflex(s) and / or eye position(s). As described elsewhere herein, various medical conditions can be assessed based on a proxy of pupil size, pupil size, pupillary reflex and, or eye position. Hence, various conditions can be assessed based on proxies of pupil size or pupillary reflex and, or on eye position. Such can be performed by comparing determined values for a proxy of pupil size, pupil size, pupillary reflex and, or eye position or proxies of pupil size or pupillary reflex and, or on eye position to respective threshold values, and, or comparing values of such for one eye compared to values of such for the other eye. Determined values that are outside (e.g., above, below)threshold values or threshold ranges of values are indictive of corresponding medical conditions.

[0289] At 814, the device 100 optionally generates, produces or otherwise provides one or more alerts. For example, the device may generate, produce or otherwise provide an alert when a condition is detected requiring medical intervention. An alert can be produced from the device 100 via a speaker, a light (e.g., LED) and, or tactile vibrator. An alert can be produced by the device transmitting a wireless signal to another device, for example a smartphone or a remotely located server.

[0290] At 816, the device 100 optionally generates, produces or otherwise provides a diagnosis. As described elsewhere herein, various medical conditions can be diagnosed based on a proxy of pupil size, pupil size, pupillary reflex and, or eye position. Hence, various conditions can be diagnosed based on proxies of pupil size or pupillary reflex and, or on eye position. Such can be performed by comparing determined values for pupil size, pupillary reflex and, or eye position or proxies of pupil size or pupillary reflex and, or on eye position to respective threshold values, and, or comparing values of such for one eye compared to values of such for the other eye. Determined values that are outside (e.g, above, below) threshold values or threshold ranges of values are indictive of corresponding medical diagnosis.

[0291] At 818, the device 100 determines if power OFF signal has been received. In response to a power OFF signal or condition, control returns to acts 804, 806 or 808. In response to an absence of a power OFF signal or condition, control passes to 820.

[0292] At 820, the device 100 terminates performance of the method 800. The device 100 may be a single use device, and rendered inoperable after termination, preventing unsafe reuse on a different subject.

[0293] Figure 9 shows a low-level method 900 of operation of a device to detect at least one of physiological characteristic(s) (e.g, proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 900 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0294] At 902, the device 100 optionally activates light emitters of a first plurality of emitters to trigger an iris reflex. In some implementations, the light emitters of the first plurality of emitters are activated to emit light in order to trigger the reflex of the iris, causing the pupil to contract. In some implementations, the light emitters of the firstplurality of emitters are not activated so do not emit light in order to prevent triggering the reflex of the iris, allowing capture of values representing a non-stimulated pupil.

[0295] At 904, the device 100 activates light emitters of a second plurality of emitters to “image” the eye by transmitting light (e.g., IR light) to the eye through the closed eyelid. The light emitted by the light emitters of the second plurality of emitters is at wavelengths suitable for traversing the closed eyelid, both in traveling to the eye and returning from the eye via the closed eyelid. Various suitable ranges of wavelengths are discussed herein.

[0296] At 906, the device 100 detects light returned from the eye through the closed eyelid by one or more light sensors. As described herein, the one or more light sensors can detect the returned light or even detect an amount (e.g. intensity) of returned light.

[0297] At 908, the device 100 determines an amount of light returned from the eye through the closed eyelid, for example using the amounts detected at 906. As previously explained, the amount of light returned from the eye is a proxy for pupil size as pupil size determines how much like passes to the retina versus how much light is reflected by portions of the eye surrounding the pupil (e.g., iris,).

[0298] At 910, the device 100 compares the determined amount of light returned to one or more threshold values. Notably, in this implementation, the device employs the amount of light in lieu of determining a size of the pupil. The threshold values can correlate to various pupil sizes, and, or to various medical conditions. The use of amount of returned light advantageously avoids computationally complicated and costly image processing, speeding up operation and allowing use of less complicated, smaller and, or more efficient processors as compared to what is used for conventional image processing (e.g., GPUs in addition to CPUs) and, or as compared to determining the pupil size itself.

[0299] At 912, the device 100 optionally determines one or more pupillary reflex values based on determined amount of light returned at successive intervals or periods of time. The device 100 can, for example, determine one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline based on the detected amount of light returned.

[0300] At 914, the device 100 compares one or more determined pupillary reflex values to respective threshold values. Such can be performed by comparing determined values for pupillary reflex or proxies of pupillary reflex to respective threshold values.Determined values that are outside (e.g., above, below) threshold values or threshold ranges of values are indictive of corresponding medical conditions.

[0301] At 916, the device 100 optionally compares one or more determined values for one eye with determined values for the other eye. As explained herein, differences between eyes can be indicative of medical conditions, for instance medical conditions requiring intervention. Such can be performed by comparing determined values for one eye with determined values for the other eye. Differences between the eyes that are outside a threshold difference are indictive of corresponding medical conditions.

[0302] Figure 10 show a low-level method 1000 of operation of a device to detect at least one of physiological characteristic(s) (e.g., proxy of pupil size, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 1000 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0303] At 1002, the device 100 optionally activates light emitters of a first plurality of emitters to trigger an iris reflex. In some implementations, the light emitters of the first plurality of emitters are activated to emit light in order to trigger the reflex of the iris, causing the pupil to contract. In some implementations, the light emitters of the first plurality of emitters are not activated so do not emit light in order to prevent triggering the reflex of the iris, allowing capture of values representing a non-stimulated pupil.

[0304] At 1004, the device 100 activates light emitters of a second plurality of emitters by transmitting light (e.g., IR light) to the eye through the closed eyelid. The light emitted by the light emitters of the second plurality of emitters is at wavelengths suitable for traversing the closed eyelid, both in traveling to the eye and returning from the eye via the closed eyelid. Various suitable ranges of wavelengths are discussed herein.

[0305] At 1006, the device 100 detects light returned from the eye through the closed eyelid by one or more light sensors. As described herein, the one or more light sensors can detect the returned light or even detect an amount (e.g. intensity) of returned light.

[0306] At 1008, the device 100 determines an amount and, or a pattern of light (e.g, spatial pattern) returned from the eye through the closed eyelid, for example using the amounts detected at 906. As previously explained, the amount of light returned from the eye is a proxy for pupil size as pupil size determines how much light passes to the retina versus how much light is reflected by portions of the eye surrounding the pupil (e.g, iris,). Hence, the device more arcuately samples light (e.g., infrared light) returned from the eye, for example detecting and, or determining at least one of an amount of light returned and, or a spatial pattern of light returned from the eye.

[0307] At 1010, the device 100 converts the determined amount and, or pattern of light returned as detected by the light sensor to a pupil size. Such can employ a stored correlation between pupil sizes and amounts and, or patterns of returned light, for example based on averages across a cohort of a population.

[0308] At 1012, the device 100 compares the determined pupil size to one or more threshold values. The threshold values can correlate to various pupil sizes, and, or to various medical conditions. The conversion of amounts of light to pupil size is computational simple. The use of amount and, or pattern of returned light advantageously avoids computationally complicated and costly image processing, speeding up operation and allowing use of less complicated, smaller and, or more efficient processors as compared to what is used for conventional image processing (e.g., GPUs in addition to CPUs).

[0309] At 1014, the device 100 optionally determines one or more pupillary reflex values based on determined pupil size or the determined amount and, or pattern of light returned at successive intervals or periods of time. The device 100 can, for example, determine one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline based on the detected amount of light returned.

[0310] At 1016, the device 100 compares one or more determined pupillary reflex values to respective threshold values. Such can be performed by comparing determined values for pupillary reflex or proxies of pupillary reflex to respective threshold values. Determined values that are outside (e.g, above, below) threshold values or threshold ranges of values are indictive of corresponding medical conditions.

[0311] At 1018, the device 100 optionally compares one or more determined values for one eye with determined values for the other eye. As explained herein, differences between eyes can be indicative of medical conditions, for instance medical conditions requiring intervention. Such can be performed by comparing determined values for one eye with determined values for the other eye. Differences between the eyes that are outside a threshold difference are indictive of corresponding medical conditions.

[0312] Figure 11 show a low-level method 1100 of operation of a device to detect at least one of physiological characteristic(s) (e.g, pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 1100 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0313] At 1102, the device 100 optionally activates light emitters of a first plurality of emitters to trigger an iris reflex. In some implementations, the light emitters of the first plurality of emitters are activated to emit light in order to trigger the reflex of the iris, causing the pupil to contract. In some implementations, the light emitters of the first plurality of emitters are not activated so do not emit light in order to prevent triggering the reflex of the iris, allowing capture of values representing a non-stimulated pupil.

[0314] At 1104, the device 100 activates light emitters of a second plurality of emitters by transmitting light (e.g., IR light) to the eye through the closed eyelid. The light emitted by the light emitters of the second plurality of emitters is at wavelengths suitable for traversing the closed eyelid, both in traveling to the eye and returning from the eye via the closed eyelid. Various suitable ranges of wavelengths are discussed herein. Hence, the device more arcuately samples light (e.g., infrared light) returned from the eye, for example detecting and, or determining at least one of an amount of light returned and, or a spatial pattern of light returned from the eye.

[0315] At 1106, the device 100 detects light returned from the eye through the closed eyelid by one or more light sensors. As described herein, the one or more light sensors can detect the returned light or even detect an amount (e.g. intensity) of returned light.

[0316] At 1108, the device 100 determines which light sensors detected light returned by light sensors which is proxy for pupil size. As previously explained, as light is reflected from portions of the eye other than the pupil, the light detectors that detect returned light provides an indication of an outline that surrounds the pupil.

[0317] At 1110, the device 100 compares which light sensors detected light returned (e.g., relative positions and / or spacing) to threshold value(s) to one or more threshold values. Notably, in this implementation, the device employs the knowledge of which light sensors detected light in lieu of determining a size of the pupil. The threshold values can correlate to various pupil sizes, and, or to various medical conditions. The use of the identify, position or relative spacing of light sensors that detect returned light advantageously avoids computationally complicated and costly image processing, speeding up operation and allowing use of less complicated, smaller and, or more efficient processors as compared to what is used for conventional image processing (e.g., GPUs in addition to CPUs) and, or as compared to determining the pupil size itself.

[0318] At 1112, the device 100 optionally determines one or more pupillary reflex values based on determined light sensor(s) that detected light returned at successive intervals or periods of time. The device 100 can, for example, determine one, more or allof: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline based on the detected amount of light returned.

[0319] At 1114, the device 100 compares one or more determined pupillary reflex values to respective threshold values. Such can be performed by comparing determined values for pupillary reflex or proxies of pupillary reflex to respective threshold values. Determined values that are outside (e.g., above, below) threshold values or threshold ranges of values are indictive of corresponding medical conditions.

[0320] At 1116, the device 100 optionally compares one or more determined values for one eye with determined values for the other eye. As explained herein, differences between eyes can be indicative of medical conditions, for instance medical conditions requiring intervention. Such can be performed by comparing determined values for one eye with determined values for the other eye. Differences between the eyes that are outside a threshold difference are indictive of corresponding medical conditions.

[0321] Figure 12 show a low-level method 1200 of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 1200 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0322] At 1202, the device 100 optionally activates light emitters of a first plurality of emitters to trigger an iris reflex. In some implementations, the light emitters of the first plurality of emitters are activated to emit light in order to trigger the reflex of the iris, causing the pupil to contract. In some implementations, the light emitters of the first plurality of emitters are not activated so do not emit light in order to prevent triggering the reflex of the iris, allowing capture of values representing a non-stimulated pupil.

[0323] At 1204, the device 100 activates light emitters of a second plurality of emitters by transmitting light (e.g., IR light) to the eye through the closed eyelid. The light emitted by the light emitters of the second plurality of emitters is at wavelengths suitable for traversing the closed eyelid, both in traveling to the eye and returning from the eye via the closed eyelid. Various suitable ranges of wavelengths are discussed herein.

[0324] At 1206, the device 100 detects light returned from the eye through the closed eyelid by one or more light sensors. As described herein, the one or more light sensors can detect the returned light or even detect an amount (e.g. intensity) of returned light.

[0325] At 1208, the device 100 determines which light sensors detected light returned by light sensors which is proxy for pupil size. As previously explained, which lightsensors detect returned light is a proxy for pupil size as pupil size determines which light rays pass through the pupil and, or which light rays are is reflected by portions of the eye surrounding the pupil (e.g., iris,).

[0326] At 1210, the device 100 converts which light sensors detected light returned (e.g., relative positions and / or spacing) to pupil size. As previously mentioned, the light sensors that detect returned light can provide a spatial pattern (e.g., an outline or a subset of perimeter points) of a perimeter that surrounds the pupil. Such is computationally less intensive than conventional image processing approaches, can speed up operation, and, or can employ less circuitry and, or simpler circuitry than conventional image processing approaches.

[0327] At 1212, the device 100 compares the determined pupil size to one or more threshold values. The threshold values can correlate to various pupil sizes, and, or to various medical conditions.

[0328] At 1214, the device 100 optionally determines one or more pupillary reflex values based on determined pupil size or based on determined light sensor(s) that detected light returned at successive intervals or periods of time. The device 100 can, for example, determine one, more or all of: baseline size, latency to constriction, constriction velocity, maximal constriction velocity, minimal size, dilation velocity, latency to return to baseline.

[0329] At 1216, the device 100 compares one or more determined pupillary reflex values to respective threshold values. Such can be performed by comparing determined values for pupillary reflex or proxies of pupillary reflex to respective threshold values. Determined values that are outside (e.g., above, below) threshold values or threshold ranges of values are indictive of corresponding medical conditions.

[0330] At 1218, the device 100 optionally compares one or more determined values for one eye with determined values for the other eye. As explained herein, differences between eyes can be indicative of medical conditions, for instance medical conditions requiring intervention. Such can be performed by comparing determined values for one eye with determined values for the other eye. Differences between the eyes that are outside a threshold difference are indictive of corresponding medical conditions.

[0331] Figure 13 show a low-level method 1300 of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 1300 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0332] At 1302, the device 100 optionally determines which light emitters of second plurality of emitters to activate based on detected eye position. As described herein, it may be advantageous to steer light emission based on detected eye position to ensure that desired portions of the eye (e.g., iris) are illuminated. Steering includes selectively activating light emitters to direct illumination in a desired or specified direction.

[0333] At 1304, the device 100 activates selected or determined light emitters to steer emission of light. Such can be performed by applying control signals to control switches that selectively couple electrical power to respective ones of the light emitters.

[0334] Figure 14 show a low-level method 1400 of operation of a device to detect at least one of physiological characteristic(s) (e.g., pupil size and / or pupillary reflex) and, or eye position, according to at least one illustrated implementation. The method 1400 can be performed as part of performing one or more of the acts of method 800 (Figure 8).

[0048] At 1402, the device 100 provides diffuse illumination from light emitters. Such can advantageously illumination the entire eye or portions thereof, without steering of illumination.Example

[0335] The inventors prepared a transpalpebral pupillometer design as a proof of concept. This transpalpebral pupillometer measures both pupil diameter and gaze direction using a concentric array of NIR LEDs and miniature photodetectors mounted on a flexible substrate.Modelling assumptions

[0336] Inventors employed an optical ray-tracing analysis using ZEMAX OPTICS STUDIO™ (Validated Optical Simulation and Design Software) that assumed (i) eyelid transmission of ~ 20%-43 %, inclusive, at 940 nm with an eyelid thickness of from 0.6 mm -1.0mm, inclusive, (ii) pupil diameters from 2 mm to 8 mm; and (iii) lateral eye rotations up to ±40° (corresponding to ~ 7.8 mm lateral pupil translation). Specific examples shown below employ an eyelid thickness of approximately 0.6 mm and eyelid transmission of approximately 43%. The model was run with a high-density photodetector array to determine the geometry and location of the maximal information and then placed a limited array of photodetectors in those areas and modelled the resulting signal.

[0337] Figures 15 A, 15B, 15C, 15D, 15E and 15F illustrate the case where a “north” LED, positioned 9 mm above the eye center, is driven. Figures 15A-15C correspond to acentered eye (9x = 0°, 9y = 0°) and Figures 15D-15F correspond to an oblique gaze (9x = 7°, 9y = 7°). When the eye is centered, photodetectors 5 and 6 (labeled on Figure 15 A) exhibit a clear monotonically decreasing irradiance as pupil diameter increases from 2 mm to 8 mm (Figure 15C), whereas the remaining detectors register minimal change. In contrast, under the oblique gaze, photodetector 4 now shows the strongest monotonic dependence on pupil diameter, while the other photodetectors become relatively insensitive (Figure 15F). This example demonstrates how the six photodetectors geometry provides directional sensitivity and enables the system to distinguish between different pupil size and gaze direction.Photodetector response for various pupil diameter and gaze directions.

[0338] Fig. 15A is a heat map of the spatial irradiance in a 20 pm X 20 pm area for a centered (9X= 0°, 9y= 0°) pupil with a 7 mm pupil diameter and Fig. 15B is a heat map of the spatial irradiance in a 20 pm X 20 pm area for a centered (9X= 0°, 9y= 0°) pupil with a 3 mm pupil diameter. Fig. 15C is a graph of corresponding measured irradiance in the six photodetectors for different pupil diameters. The placements of the 6 photodetectors are outlined and labeled in white in Fig. 15 A, where the photodetectors are placed around a 5 mm radius ring. Fig. 15D is a heat map of the spatial irradiance for an oblique gaze direction (rotation angles 9X= 7°, 9y= 7°) with a 7 mm pupil diameter and Fig. 15E is a heat map of the spatial irradiance for an oblique gaze direction (rotation angles 9X= 7°, 9y= 7°) with 3 mm pupil diameter. Fig. 15D is a graph of corresponding measured irradiance in the six photodetectors for different pupil diameters.Design rationale

[0339] The device was designed with a 9 mm IR LED radius to balance the differential signal in the photodetectors at the extreme gaze directions while retaining adequate irradiance at central gaze. Reducing the radius below 9 mm increases signal strength for central gaze but causes signal ambiguity at large rotations; increasing the radius beyond 9 mm directs illumination primarily onto the sclera, reducing iris and pupil- dependent modulation. The choice of six photodetectors balances angular coverage with mechanical flexibility or compliance or conformability of the substrate. The locations of the six photodetectors evenly spaced around a 5 mm radius were found to provide distinguishable irradiance differences across the full range of pupil diameters (Figure 15A-15C) and gaze directions (Figure 15D-15F). Six visible LEDs are evenly spaced on a 7 mm radius ring, with a seventh visible LED at the center. The 7 mm LED ring maps tothe eye rotations of -35°, allowing selective stimulation of the pupil at each of the nine cardinal gaze directions.Device configuration

[0340] In an example implementation, eight 940 nm IRLEDs (1 pm x 0.5 pm x 0.5 pm) (illustrated as hexagonal shapes for ease of recognition) are positioned on a circle of 9 mm radius around the pupil center. Six silicon photodiodes (2 pm x 1.8 pm x 0.6 pm) (illustrated as square shapes for ease of recognition) are positioned on a concentric circle of 5 mm radius. The IR LED ring provides eight evenly spaced illumination vectors corresponding to the principal horizontal, vertical, and oblique gaze directions(0°, ±45°, ±90°, ±135°, 180°). The photodetector ring samples the scattered IR light from the iris and pupil region, with sufficient angular diversity to resolve both pupil diameter and lateral displacement (Fig. 16).Device Design

[0341] As illustrated in Fig. 16, eight NIR LEDs are arranged in a circle with 9 mm radius centered around the pupil. Photodetectors are positioned on a concentric circle of 5 mm radius. Seven visible light LEDs (illustrated as circular shapes for ease of recognition) are positioned, one in the center and the remaining 6 in a ring with a 7 mm radius.Frequency and Intensity of Irradiance and Safety of IR Light Exposure

[0342] To ensure compliance with photobiological safety standards according to ANSI Z80.36-2021; Ophthalmics - Light Hazard Protection for Ophthalmic Instruments or IEC 62471:2006, the optical exposure of the exemplary device was evaluated at the cornea and retina. A conservative worst-case scenario was assumed where the eyelid transmission at 940 nm is roughly Tiid = 43%1and the transmission through the remaining ocular media is To = 50%2, with all transmitted light entering a fully dilated pupil and reaching the retina. It was further assumed that the 940 nm LED is placed directly on the closed upper eyelid and approximate the distance from the LED to the cornea to be d = 0.5 mm, which is two standard deviations below the LED thickness (0.5 ± 0.1 mm) and the thinnest part of the eyelid (0.3 ± 0.05 mm).

[0343] With an LED radiant intensity of IIR = 5 X 10'3W / sr and viewing angle of 9 = 140°, an overestimation of the power emitted from the LED is P = IIR* £1 = IIR* 2TT 1 — cos = * 4.13 = 20.7 X 10-3VF, assuming a uniform radiantintensity across the 140° cone. (In reality, our emitter is approximately Lambertian, wherethe power P = IIR* n = 15.7 x 103W). Then the incident irradiance (EIR) at the cornea pis calculated with the equation E1R= TUdwhere Tiid is the eyelid transmission (0.43) and A is the spot area on the cornea based on the LED distance and beam divergence. For d = 0.5 mm, the spot radius is r = d * tan = 1.37 x 10-3m, with the corresponding spot area A = 5.9 x 10-6m2and irradiance EIR= 1500^. It is noted that this irradiance level is above the continuous (t > 1000 s) exposure limit for cornea (100 W / m2), but remains safely below the short-term limit, given by E = 18000 * t-0 75= w3200 — for t = 10 s. It was decided to deliver a pulsed IR light at 60 Hz, with 5% duty cycle, so the exposure time for the pulsed light will be t = 8.33 x 10-4s, which is well below the maximum exposure time, and the irradiance corresponding to the time averaged power for continuous pulsed illumination is EIR = 75 W / m2, which is below the continuous exposure limit (100 W / m2).

[0344] Furthermore, in the eye-mask design, the distance from the LED to the cornea will likely exceed the d = 0.5 mm due to spacing between the mask and the eyelid and spatial variations in eyelid thickness. To account for variations in the distance between the LED and cornea, a maximum allowable exposure time for a single pulse as a function of LED-to-cornea distance is illustrated in Figure 17A, confirming that the exposure remains within safe limits for a single pulse time t < 10 s (red dashed line). If the IR LED is 2 mm (or more) away from the cornea, then the irradiance is within the continuous exposure safety limit (<100 W / m2). The maximum allowable duty cycle as a function of LED-to-cornea distance for a continuous pulsed illumination operating at 60 Hz is then calculated. Figure 17B confirms that with a duty cycle of 5% (red dashed line), the device will operate under the continuous exposure limit.

[0345] For retinal hazard evaluation, the radiance at the retina with an LED placed 0.5 mm away from the cornea surface is calculated. The diameter of the human eye ranges from the lower limit of 16 mm in children to 24 mm in adults, thus we assume a10 ?7l??conservative eyJe size of 16 mm. With an angular subtense a = - - = 0.0625 rad and ° 16 mm8.9 X 10-7m2. With a radiant intensity at the retina of Let = 1.08 x 10'3W / sr (LED intensity after 43% eyelid transmission and 50% ocular transmission), the retinal radiance normalized with the burn hazard ratio for 940 nm (R(l) = | Q7()0 11111<1 'soonm])scalculated,giving the normalized retinal radiance LIR =R(l)*Iret / Aret = 402 W / (m2*sr), which is well below the continuous source exposure limit of Liimit =6000 / a = 96000 W / (m2*sr). Thus, the limiting factor for the maximum exposure time for the IR LED will be dependent on the irradiance on the cornea.Safety of Visible Light Exposure for Triggering Pupillary Light Reflex

[0346] Using the same LED geometry, emission profile, and modeling framework for the 940 nm IR LED, we calculate the retinal safety in the visible wavelength range determined by the blue hazard function (Figs. 17A, 17B, 17C, 17D), where the radiance exposure limit is much lower for blue light. The exposure limit on the cornea can be ignored since the hazard in the visible wavelength range is limited by the retina (IEC 62741 :2006). Figure 17D shows the radiance at the retina for different visible wavelengths with an LED radiant intensity of 5 mW / sr and the continuous exposure safety limit given by LB(X) = 100 / B(l) W / (m2*sr) where B(l) is the blue hazard function. It is noted that even for continuous exposure, the visible LED light is below the safety limit. Thus, for triggering the pupillary light reflex, where the eyes are continuously illuminated for 0.2 sec, the device will operate well within the safety limit.

[0347] Figure 17A shows cornea safety calculations for NIR Light with a maximum exposure time for single pulse of 940 nm IR LED at different distances from the cornea. The red dotted line shows exposure time of t = 10 s, which far longer than the pulsed light duration that the device will use in this proposal (t = 8.33 x 10-4s), which will keep device operation far below (within) the safety threshold for all distances. Figure 17B shows a maximum duty cycle for continuous IR light at different distances from the cornea. Even at the closest possible distance of 0.5 mm and a duty cycle of 5%, the device operates below (within) the safety threshold. Figure 17C shows retina safety calculations for visible light consistent with the blue hazard function as set out in various photobiological safety standards (e.g., IEC 62471 . The blue hazard normalization function at the retina showing steep drop off in retinal hazard at wavelengths above 500 nm. In Figure 17D the red line (upper-most line in graph) shows a safety limit for continuous exposure at the retina, the blue line (intermediate line in graph) shows radiance at the retina for continuous light exposure at the intensity the device will use (5 mW / sr), while the gray line (lower-most line in graph) shows that radiance at the retina for pulsed light with a 2% duty cycle at 5 mW / sr (the intensity the exemplary device uses) is below (within) the safety limit. The green, amber and red stars show the radiance tothe retina for the wavelengths and duty cycles we will be using (520nm, 600 nm, 630 nm) in the exemplary device will be well below retinal safety limits.Safety of Visible Light Exposure for Light Therapy

[0348] For red light therapy, if the exemplary device continuously illuminate the eyes for 30 minutes, and for pulsed blue light therapy, if the exemplary device delivers a 2 second pulses every 30 seconds (6.67% duty cycle) for 30 minutes, the exemplary device will operate well below (within) the safety limit.

[0349] In Figure 18, the red line (upper-most line in graph) shows retina safety calculations safety limit for continuous exposure at the retina, the blue line (intermediate line in graph) shows radiance at the retina for continuous light exposure at the intensity used by the exemplary device (5 mW / sr). A blue star shows continuous red-light therapy for 30 minutes. The gray line (lower-most line in graph) shows radiance at the retina for pulsed light with a 6.67% duty cycle at 5 mW / sr (the intensity used by the exemplary device) is below (within) the safety limit. The blue stars show that 2 second pulses every 30 seconds (6.67% duty cycle) for 30 minutes will be well below (within) the safety limit will be well below (within) retinal safety limits.Post-Amble

[0350] The foregoing detailed description has set forth various implementations of the devices and / or processes via the use of block diagrams, schematics, and examples.Insofar as such block diagrams, schematics, and examples contain one or more functions and / or operations, it will be understood by those skilled in the art that each function and / or operation within such block diagrams, flowcharts, or examples can be implemented, individually and / or collectively, by a wide range of hardware, software, firmware, or virtually any combination thereof. In one implementation, the present subject matter may be implemented via Application Specific Integrated Circuits (ASICs). However, those skilled in the art will recognize that the implementations disclosed herein, in whole or in part, can be equivalently implemented in standard integrated circuits, as one or more computer programs running on one or more computers (e.g., as one or more programs running on one or more computer systems), as one or more programs running on one or more controllers (e.g., microcontrollers) as one or more programs running on one or more processors (e.g., microprocessors), as firmware, or as virtually any combination thereof, and that designing the circuitry and / or writing the code for thesoftware and or firmware would be well within the skill of one of ordinary skill in the art in light of this disclosure.

[0351] Various processes and structures presented herein are not inherently related to any particular computer or other apparatus. Various general-purpose systems may be used with processor-executable logic in accordance with the teachings herein, or it may prove convenient to construct a specialized hardware (e.g., ASIC, FPGA) to perform the algorithm. In addition, Various embodiments and implementations are not described with reference to any particular programming language. It will be appreciated that a variety of programming languages may be used to implement the teachings described herein.

[0352] Various embodiments and implementations are described in the general context of computer-executable instructions, such as program modules, executed by a processorbased system or device. Generally, program modules include routines, programs, objects, components, data structures, and so forth, which perform particular tasks or implement particular abstract data types. The various embodiments and implementations are may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote computer storage media including memory storage devices.

[0353] This application incorporates the teachings of U.S. patent application 63 / 744,948 filed January 14, 2025; and U.S. patent application 63 / 820,249 filed June 9, 2025, in their entireties.

[0354] The above-described method(s), process(es), or technique(s) may include various acts, though those of skill in the art will appreciate that in alternative examples certain acts may be omitted and / or additional acts may be added. Those of skill in the art will appreciate that the illustrated order of the acts is shown for exemplary purposes only and may change in alternative examples. Some of the exemplary acts or operations of the above-described method(s), process(es), or technique(s) are performed iteratively. Some acts of the above-described method(s), process(es), or technique(s) can be performed during each iteration, after a plurality of iterations, or at the end of all the iterations.

[0355] The above-described method(s), process(es), or technique(s) could be implemented by a series of processor readable instructions stored on one or more non-transitory processor-readable media. Some examples of the above described method(s), process(es), or technique(s) method are performed in part by a specialized device such as an adiabatic quantum computer or a quantum annealer or a system to program orotherwise control operation of an adiabatic quantum computer or a quantum annealer, for instance a computer that includes at least one digital processor. The above-described method(s), process(es), or technique(s) may include various acts, though those of skill in the art will appreciate that in alternative examples certain acts may be omitted and / or additional acts may be added. Those of skill in the art will appreciate that the illustrated order of the acts is shown for example purposes only and may change in alternative examples. Some of the example acts or operations of the above-described method(s), process(es), or technique(s) are performed iteratively. Some acts of the above-described method(s), process(es), or technique(s) can be performed during each iteration, after a plurality of iterations, or at the end of all the iterations.

[0356] The above description of illustrated implementations, including what is described in the Abstract, is not intended to be exhaustive or to limit the implementations to the precise forms disclosed. Although specific implementations of and examples are described herein for illustrative purposes, various equivalent modifications can be made without departing from the spirit and scope of the disclosure, as will be recognized by those skilled in the relevant art. The teachings provided herein of the various implementations can be applied to other methods of quantum computation, not necessarily the example methods for quantum computation generally described above.

[0357] The various implementations described above can be combined to provide further implementations.

[0358] The above description of illustrated implementations, including what is described in the Abstract, is not intended to be exhaustive or to limit the implementations to the precise forms disclosed. These and other changes can be made to the implementations in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific implementations disclosed in the specification and the claims, but should be construed to include all possible implementations along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Claims

CLAIMSI / We claim:

1. A device to detect through at least one closed eyelid at least one of a pupil size, a pupillary light reflex, or an eye position of an eye having an iris, a pupil, and a vitreous, the device comprising:a substrate comprising at least one electrically insulative layer and one or more circuit traces, the substrate being conformable to a portion of the eye when the substrate is positioned over or on an outer surface the at least one closed eyelid, the substrate comprising a central region and a peripheral region, the central region which overlies the iris and the pupil of the eye when the device is positioned over or on the outer surface of the at least one closed eyelid and the peripheral region spaced radially outward of the central region;a first plurality of light emitters carried by the substrate and electrically coupled to the one or more circuit traces, the light emitters of the first plurality of light emitters operable to emit light in a first range of wavelengths to stimulate a reflex of the iris of the eye, the light emitters of the first plurality of light emitters are oriented to transmit light toward the pupil when the substrate is positioned over or on the outer surface of the closed eyelid;a second plurality of light emitters carried by the substrate and electrically coupled to the one or more circuit traces, the light emitters of the second plurality of light emitters operable to emit light in a second range of wavelengths, the light emitters of the second plurality of light emitters positioned in the peripheral region of the substrate spaced radially outward from the central region of the substrate and oriented to transmit light a shallow angle where a respective principal axis of emission of each of the light emitters of the second plurality of light emitters does not intersect the vitreous of the eye when the substrate is positioned over or on the outer surface of the at least one closed eyelid; anda plurality of light sensors carried by the substrate and electrically coupled to the one or more circuit traces, the light sensors of the plurality of light sensors positioned and oriented to receive light returned from the iris when the substrate ispositioned over or on the outer surface to the at least one closed eyelid.

2. The device according to claim 1, wherein the light emitters of the second plurality of light emitters are light emitting diodes which each have a respective principal axis of emission and the respective principal axis of emission is tangentially to the vitreous of the eye when the substrate is positioned over or on the outer surface of the at least one closed eyelid.

3. The device according to claim 1, wherein the light emitters of the first plurality of light emitters are light emitting diodes.

4. The device according to claim 1, wherein the first range of wavelengths includes wavelengths between 400 nm inclusive and 700 nm inclusive.

5. The device according to claim 1, wherein the first range of wavelengths includes wavelengths between 520 nm and 650 nm.

6. The device according to claim 1, wherein the light emitters of the second plurality of light emitters are light emitting diodes.

7. The device according to claim 1, wherein the light emitters of the second plurality of light emitters are micro-light emitting diodes.

8. The device according to claim 1, wherein the second range of wavelengths includes wavelengths between 800 nm inclusive and 2500 nm inclusive.

9. The device according to claim 1, wherein the second range of wavelengths includes wavelengths between 900 nm inclusive and 2500 nm inclusive.

10. The device according to claim 1, wherein the light sensors of the plurality of light sensors are photodiodes.

11. The device according to claim 1, wherein the light sensors of the plurality of light sensors are Si, GaAs, InGaAs, InGaAs, InGaAs, InGaAs, InAs, InSb, InAsSb, InAsSb, HgCdTe, Ge, PbS, or PbSe based sensors.

12. The device according to claim 1, wherein the light sensors of the plurality of light sensors are responsive to light in the second range of wavelengths.

13. The device according to claim 1, wherein the substrate is one or more flexible printed circuit boards and includes one or more strain relief features to enhance conformability of the substrate.

14. The device according to claim 1, further comprising:a transmitter carried by the substrate and electrically coupled to the one or more circuit traces;an antenna communicatively coupled to the transmitter and operable to transmit signals from the device.

15. The device according to claim 1, further comprising:a bio-compatible adhesive carried on a surface of the substrate.

16. The device according to claim 15, wherein the adhesive is a pressure sensitive adhesive, and further comprising:a release liner removably covering the pressure sensitive adhesive prior to use.

17. The device according to claim 15, wherein the substrate is sized to cover both of the at least one eyelids when secured to the at least one closed eyelid.

18. The device according to claim 1, further comprising:an eye mask, wherein the substrate is physically coupled to the eye mask.

19. The device according to claim 1, wherein the light emitters of the first plurality of light emitters are positioned in the central region of the substrate.

20. The device according to claim 1 wherein the light emitters of the first plurality of light emitters are dispersed across the central region and the peripheral region of the substrate.

21. The device according to claim 1, wherein the light emitters of the second plurality of light emitters are angularly arrayed about a central axis and the light sensors of the plurality of light sensors are angularly arrayed about the central axis.

22. The device according to claim 21, wherein the light emitters of the second plurality of light emitters are angularly spaced equally from one another about the central axis and the light sensors of the plurality of light sensors are angularly spaced equally from one another about the central axis.

23. The device according to claim 22, wherein the light emitters of the second plurality of light emitters are spaced at a first distance from the central axis and the light sensors of the plurality of light sensors are spaced at a second distance from the central axis.

24. The device according to claim 23, wherein the first distance from the central axis is between approximately 8mm and approximately 10mm, inclusive, and preferably approximately 9mm, where approximately means plus or minus 10%.

25. The device according to claim 24, wherein the second distance from the central axis is between approximately 4mm and approximately 6mm, inclusive, and preferably approximately 5mm, where approximately means plus or minus 10%.

26. The device according to any of claims 21 through 25, wherein the second plurality of light emitters includes eight light emitters, arrayed at approximately 45° from one another about the central axis, where approximately means plus or minus 10%.

27. The device according to any of claims 21 through 25, wherein the light emitters of the first plurality of light emitters include a first set of three or more light emitters that are angularly arrayed about the central axis.

28. The device according to claim 27, wherein the light emitters of the first set of three or more light emitters of the first plurality of light emitters are angularly spaced equally from one another about the central axis.

29. The device according to claim 27, wherein the light emitters of the first set of three or more light emitters of the first plurality of light emitters are angular arrayed midway between each light emitter of a corresponding closest pair of light emitters of the second plurality of light emitters to maximize a distance from the light emitters of the corresponding closest pair of light emitters of the second plurality of light emitters.

30. The device according to claim 27, wherein the light emitters of the first plurality of light emitters include a second set of one or more light emitters that spaced radially inward of the first set of three or more light emitters of the first plurality of light emitters.

31. The device according to claim 30, wherein the second set of one or more light emitters includes a single light emitter that is coaxial with the central axis.

32. The device according to claim 31, wherein the first set of three or more light emitters of the first plurality of light emitters are spaced at a third distance from the central axis.

33. The device according to claim 32, wherein the third distance from the central axis is between approximately 6mm and approximately 8mm, inclusive, and preferably approximately 7mm, where approximately means plus or minus 10%.

34. The device according to any of claims 21 through 25, wherein the light emitters of the first plurality of light emitters are spaced radially inward from the light emitters of the second plurality of light emitters.

35. The device according to any of claims 21 through 25, wherein the light emitters of the first plurality of light emitters includes nine light emitters, with eight of the nine light emitters radially spaced outward from the central axis.

36. The device according to claim 34, wherein the light emitters of the second plurality of light emitters includes eight light emitters.

37. The device according to claim 21, wherein the light emitters of the second plurality of light emitters are angularly spaced unequally from one another about the central axis and the light sensors of the plurality of light sensors are angularly spaced unequally from one another about the central axis.

38. The device according to claim 37, wherein the first plurality of light sensors are spaced radially inward of the light emitters of the second plurality of light emitters.

39. The device according to claim 38, wherein the first plurality of light sensors includes eight light sensors, located as respective locations.

40. The device according to claim 39, wherein the light sensors of the first plurality of light sensors are angular arrayed at approximately 32 degrees, 90 degrees, 148 degrees, 204 degrees, 236 degrees, 270 degrees, 304 degrees, and 336 degrees, about the central axis, successively counterclockwise starting from an X axis of an XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

41. The device according to claim 40, wherein the light sensors of the first plurality of light sensors are spaced from the central axis by approximately 5.545mm, 3.387mm, 5.545mm, 6.41mm, 5.737mm, 4.727mm, 5.737mm, and 6.41mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

42. The device according to any of claims 40 or 41, wherein the second plurality of light emitters includes twelve light emitters, located at respective locations.

43. The device according to claim 42, wherein the light emitters of the second plurality of light emitters are spaced approximately at 2 degrees, 23 degrees, 55 degrees, 90 degrees, 125 degrees, 157 degrees, 178 degrees, 199 degrees, 233 degrees, 270 degrees, 307 degrees, and 341 degrees, about the central axis, successively counterclockwise starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

44. The device according to claim 43, wherein the light emitters of the second plurality of light emitters are spaced from the central axis by approximately distances, 8.324mm, 7.502mm, 6.853mm, 5.904mm, 6.853mm, 7.502mm, 8.324mm, 8.895mm, 7.777mm, 9.129mm, 7.777mm, and 8.895mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

45. The device according to any of claims 40 through 44, wherein the first plurality of light emitters includes seven light emitters, located at respective locations.

46. The device according to claim 45, wherein the light emitters of the first plurality of light emitters are spaced approximately at 0 degrees, 90 degrees, 180 degrees, 236 degrees, 249 degrees, 291 degrees, and 304 degrees, about the central axis, successively counterclockwise starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

47. The device according to claim 46, wherein the light emitters of the first plurality of light emitters are spaced from the central axis by approximately distances, 4.000mm, 1.000mm, 4.000mm, 3.606mm, 8.544mm, 8.544mm, and 3.606mm, respectively successively counterclockwise about the central axis starting from the X axis of the XY plane to which the central axis is perpendicular, where approximately means plus or minus 10%.

48. The device according to claim 1, wherein the orientation of emission of the light emitters of the first plurality of light emitters is steerable.

49. The device according to claim 1, wherein the orientation of emission of the light emitters of the first plurality of light emitters steered by selectively controlling which of the light emitters of the first plurality of light emitters to activate in response to a detected eye position of the eye.

50. The device according to claim 1, wherein the light sensors of the plurality of light sensors are positioned in the central region of the substrate.

51. The device according to claim 1, wherein the light sensors of the plurality of light sensors are positioned in the central region and the peripheral region of the substrate.

52. A system to detect through at least one closed eyelid at least one of a pupil size, a pupillary light reflex, or an eye position of an eye having an iris, a pupil, and a vitreous, the system comprising:at least one instance of the device of any one of claims 1 through 48;at least one processor communicatively coupled to the device; andat least one processor-readable medium communicatively coupled to the at least one processor, the at least one processor-readable medium which stores processorexecutable instructions which, when executed by the at least one processor, cause the at least one processor to:detect a value representative of at least one of the pupil size or the pupillary lightreflex based on light returned from the iris and detected by one or more of the light sensors of the plurality of light sensors.

53. The system according to claim 52, wherein to detect the value representative of the pupil size the processor-executable instructions, when executed by the at least one processor, cause the at least one processor to determine which of the light sensors detect light returned from the iris.

54. The system according to claim 52, wherein to detect the value representative of the pupillary light reflex the processor-executable instructions, when executed by the at least one processor, cause the at least one processor to determine an amount of time between activation of the light emitters of the first plurality of light emitters and detection of light returned from the iris by one or more of the light sensors of the plurality of light sensors.

55. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, cause the at least one processor further to:detect the eye position of the eye based on light returned from the iris and detected by one or more of the light sensors of the plurality of light sensors.

56. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, cause the at least one processor further to detect the eye position of the eye based on which of the one or more of the light sensors of the plurality of light sensors detect light returned from the iris.

57. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, cause the light emitters of the second plurality of light emitters to emit light sequentially with respect to one another.

58. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, samples the light sensors of the plurality of light sensors a defined delay time after activation of the light emitters of the first plurality of light emitters.

59. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, determines a neurological state of a subject.

60. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, determines a neurological state of a subject via at least one of machine-learning or an artificial neural network.

61. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, determines a sleep state of a subject.

62. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, determines if one or more conditions is outside of a threshold and in response generates an alert.

63. The system according to claim 52, wherein the processor-executable instructions, when executed by the at least one processor, generates a notification.

64. The system according to claim 52, further comprising:detecting the eye position of the eye; andsteering an orientation of emission of the light emitters of the first plurality of light emitters based at least in part on the eye position of the eye to steer the light emitted by the light emitters of the first plurality of light emitters.

65. The system according to claim 64, wherein steering the orientation of emission of the light emitters of the first plurality of light emitters includes selectively controlling which of the light emitters of the first plurality of light emitters is active based at least in part on the eye position of the eye to steer the light emitted by the light emitters of the first plurality of light emitters.

66. A method of operating a system to detect at least one of a physiologic eye characteristic or an eye position of an eye through at least one closed eyelid, the eye having an iris, a pupil, and a vitreous, the system comprising at least one processor; and at least one processor-readable medium communicatively coupled to the at least one processor, the at least one processor-readable medium which stores processor-executable instructions which are executed by the at least one processor, the method comprising: transmitting light of a first set of wavelengths toward the closed eyelid of eye; and detecting light returned from the eye via the closed eyelid by one or more light sensors; andassessing a condition of a subject based at least in part on at least one of an amount and pattern of light detected or based on which light sensors detected light returned from the eye via the closed eyelid.

67. The method according to claim 66, wherein assessing the condition of the subject based at least in part on at least one of an amount and a pattern of light detected or based on which light sensors detected light returned from the eye via the closed eyelid is performed without determining a pupil size.

68. The method according to claim 66, wherein assessing the condition of the subject based at least in part on at least one of an amount and a pattern of light detected or based on which light sensors detected light returned from the eye via the closed eyelid is performed without performing image processing.

69. The method according to claim 66, further comprising:converting at least one of an amount and a pattern of light detected or based on which light sensors detected light returned from the eye via the closed eyelid to acorresponding pupil size.

70. The method according to claim 66, further comprising:transmitting light of a second set of wavelengths to trigger an iris reflex before detecting light returned from the eye via the closed eyelid by one or more light sensors, the second set of wavelengths different from the first set of wavelengths.

71. The method according to claim 70, wherein transmitting light of the second set of wavelengths includes directing diffuse light toward the eye.

72. The method according to claim 66, further comprising:detecting a position of the eye.

73. The method according to claim 72, further comprising:selecting one or more light emitters of a set of light emitters to activate based on the detected eye position of the eye.

74. The method according to claim 72, wherein assessing the condition of the subject is based at least in part on the detected eye position of the eye.

75. The method according to claim 66, further comprising:determining one or more pupillary reflex values based on two or more successive detected eye physiological characteristics.

76. The method according to claim 75, wherein assessing the condition of the subject is further based on the determined one or more pupillary reflexes.

77. The method according to claim 66, wherein assessing the condition of the subject is further based on a determined eye position of the eye.

78. The method according to claim 66, further comprising:inferring at least one of a pupil size or a pupillary light reflex based on lightreturned from the iris and detected by one or more of the light sensors.

79. The method according to claim 66, wherein transmitting light of the first set of wavelengths toward the closed eyelid of eye includes directing diffuse light toward the eye.

80. The method according to claim 66, further comprising:performing a calibration.

81. The method according to claim 66, further comprising:generate one or more alerts.

82. The method according to claim 66, further comprising:generate a diagnosis.

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