Optical coherence tomography (OCT) system for measuring retinal thickness

Abstract

Optical coherence tomography (OCT) systems and methods are provided [Solution] Improved optical coherence tomography systems and methods for measuring retinal thickness are presented. The systems are compact, handheld, provide in-home monitoring, allow patients to measure themselves, and can be rugged enough to withstand a drop while still reliably measuring the retina. In one embodiment, the compact OCT system measures thickness changes in the retina with an accuracy (or repeatability) less than the axial resolution of the compact OCT system, and the thickness changes in the retina comprise a first thickness at a first time and a second thickness at a second time.

Description

Technical Field

[0001] (Cross-reference) This application claims priority to U.S. Provisional Patent Application No. 62 / 437,486 (filed Dec. 21, 2016, titled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications"), U.S. Provisional Patent Application No. 62 / 539,382 (filed Jul. 31, 2017, titled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications"), U.S. Provisional Patent Application No. 62 / 546,935 (filed Aug. 17, 2017, titled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications"), and U.S. Provisional Patent Application No. 62 / 547,314 (filed Aug. 18, 2017, titled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications"), the entire contents of which are hereby incorporated by reference for all purposes. [[ID=⑨]]

Background Art

[0002] The eye is important for vision, and people need to see. The eye has a cornea and a lens that refract light and form an image on the retina. The retina generates electrical signals in response to the image formed thereon, and these electrical signals are transmitted to the brain via the optic nerve. The fovea and macula of the retina have an increased density of cones relative to other areas of the retina and provide sharp and clear vision. Unfortunately, retinal diseases can affect vision even if other parts of the eye, such as the cornea and lens, are healthy.

[0003] Retinal thickness can be used to diagnose and monitor retinal health. Many patients diagnosed with retinal vascular disease and other diseases or conditions have elevated retinal thickness and are taking or being treated with medications. Macular edema is an example of elevated retinal thickness, often associated with other conditions such as diabetes. Macular edema can be associated with other conditions such as age-related macular degeneration, uveitis, occlusion of the retinal vascular system, and glaucoma. It would be helpful to quickly determine whether medications are not working or require readmission so that treatment can be modified accordingly and vision can be preserved. One approach used to measure retinal thickness is optical coherence tomography (OCT).

[0004] Unfortunately, many older OCT systems are overly complex and expensive, making them unsuitable for regular monitoring of retinal thickness, such as weekly or daily. Previous standards of eye treatment involved visits to a healthcare provider to measure retinal thickness, but such visits require scheduling and appointments and can be expensive, especially if performed weekly or daily. Many older OCT systems are unsuitable for home monitoring or mobile healthcare. Such systems are typically heavier than what an individual can easily carry and are unsuitable for transport with patients. In addition, older OCT systems are more complex than they would ideally be, making them unsuitable for daily use and the risk of dropping them. The cost of older OCT systems can exceed what a typical patient can afford. Furthermore, the use of older OCT systems may require a trained operator. For the reasons above, home monitoring of retinal thickness has not been adopted, as previous standards of treatment and previous treatment for patients with retinal disease may not ideally meet the requirements in many cases.

[0005] Based on the above, it would be helpful to have an improved OCT system and method for measuring retinal thickness. Ideally, such a system would be small, handheld, provide home monitoring, allow the patient to measure themselves, and still be robust enough to withstand drops while reliably measuring the retina. [Overview of the project] [Means for solving the problem]

[0006] The compact optical coherence tomography (OCT) systems and methods disclosed herein enable in-home and mobile monitoring of retinal thickness. While specifically referring to the measurement of retinal thickness, the compact OCT systems and methods disclosed herein will find applications in many fields, including microscopy, metrology, aerospace, astronomy, telecommunications, medicine, pharmaceuticals, dermatology, dentistry, and cardiology.

[0007] Miniature OCT systems comprise multiple components arranged to provide optical path and weight reduction. In many embodiments, miniature OCT systems are configured to measure changes in retinal thickness that are below the resolution value of the OCT system, which allows for a significant reduction in size, cost, and complexity. The system has sufficient repeatability and reproducibility to accurately detect changes in retinal thickness that are smaller than the system axial resolution value. Miniature OCT systems are capable of scanning a wavelength range at a sufficient speed to acquire OCT data, thereby reducing errors associated with system movement with respect to the eye. In many embodiments, miniature OCT systems are calibrated to specific patients using a clinical reference system with a higher resolution than the miniature OCT system, and the miniature OCT system is calibrated to specific patients based on retinal thickness measured using the clinical reference system. In some cases, miniature OCT systems are equipped with calibration kits or devices that allow the system to be tested to ensure that repeatability and reproducibility remain within acceptable tolerances.

[0008] In some cases, a miniature OCT system is configured to be held in the user's hand for the patient to measure themselves. Alternatively, the miniature OCT system may be configured to be mounted on a table stand or on the user's head. In some embodiments, the miniature OCT system includes a visible target for the patient to align themselves with a miniature spectrometer while the patient holds the system's measuring components in their hand. The miniature OCT system includes a housing for containing the measuring components, which in some cases is sized so that the user can easily grasp the housing, lift the measuring components within the housing, and align the OCT system with their eye. The miniaturization and reduced mass of the OCT system allow the system to be easily held in the patient's hand and transported with the patient. In many embodiments, the tomography system has a maximum transverse dimension ranging from about 80 mm to about 160 mm and a mass ranging from about 100 grams to about 500 grams. In many embodiments, the OCT system is configured without internal moving parts to increase the reliability of the system. The compact OCT system is configured to be dropped at will from a distance of approximately 1 foot and to provide repeatability and accuracy in measuring retinal thickness of, for example, approximately 25 μm or less.

[0009] In some embodiments, a compact OCT system comprises a light source configured to emit multiple wavelengths, a detector, optical elements positioned to generate optical interference signals on the detector, and circuits coupled to the detector and the light source. In some embodiments, the light source is configured to emit a light beam of varying wavelengths to sweep wavelengths over a range of wavelengths. In one example, the wavelength is swept over a range of approximately 3 nm to 10 nm to measure retinal thickness. This range can provide reduced system complexity and cost with sufficient axial resolution, repeatability, and reproducibility to determine changes in retinal thickness of 25 μm or less, although longer wavelength sweeps can be used. In some embodiments, a sweep range of 3 nm to 10 nm for an OCT system allows, for example, a compact OCT system to detect retinal thicknesses greater than approximately 150 μm and changes in retinal thickness as small as 25 μm, although longer wavelength sweeps can be used. In some embodiments, the circuit is configured to drive the light source using a waveform having a characteristic period and sweep frequency, such as a sawtooth waveform. In one example, the circuit is coupled to a detector to measure the frequency of interference signals from light reflected from the eye and determine the thickness of the retina, but the thickness of other objects can also be measured. In some embodiments, the circuit is configured to drive a light source above the maximum rated current threshold for a portion of the waveform and below the maximum rated current threshold for another portion of the waveform, so that the light source emits light between both portions of the waveform. This overdriving of the light source within a portion of the waveform allows for an extended wavelength range of the light source and an increased measurement range, along with a reduction in the complexity, size, and weight of the OCT system. The present invention provides, for example, the following: (Item 1) A compact optical coherence tomography (OCT) system for measuring the thickness of the retina, wherein the compact OCT system is Detector and A light source configured to generate a light beam having multiple wavelengths, A plurality of optical elements coupled to the light source, wherein the plurality of optical elements direct the beam into the eye and generate an interference signal in the detector, The detector and the circuit coupled to the light source Equipped with, The circuit is a compact OCT system that determines the thickness of the retina in response to the signal. (Item 2) The miniature OCT system according to item 1, wherein the miniature OCT system measures changes in thickness in the retina with an accuracy (or repeatability) smaller than the axial resolution of the miniature OCT system, and the changes in thickness in the retina comprise a first thickness at a first time and a second thickness at a second time. (Item 3) The small OCT system described in item 1, wherein the change in retinal thickness measured using the small OCT system is smaller than the axial resolution of the small OCT system. (Item 4) The compact OCT system described in item 2, wherein the axial resolution has a resolution value in the range of approximately 150 μm to approximately 30 μm, and optionally, the said value is in the range of approximately 150 μm to approximately 75 μm. (Item 5) The compact OCT system according to item 1, wherein the light beam has a variable wavelength, and the circuit is configured to vary the wavelength using a drive current from the circuit. (Item 6) The miniature OCT system according to item 1, wherein the thickness of the retina comprises the distance between the first layer of the retina and the second layer of the retina, and the thickness of the retina is greater than 150 μm. (Item 7) The compact OCT system according to item 1, wherein the thickness of the retina is in the range of approximately 150 to 300 μm, the wavelength range is swept in the range of approximately 2 nm to approximately 10 nm, the OCT system has an axial resolution in the range of approximately 150 μm to approximately 30 μm, optionally the wavelength range is swept from approximately 3 nm to approximately 6 nm, the axial resolution is in the range of approximately 100 μm to approximately 50 μm, and optionally the light source comprises a single VSCEL. (Item 8) The repeatability between consecutive measurements of the retina is within 25 μm, and the reproducibility between measurements over a longer period of at least one week is within 25 μm, and optionally, the reproducibility is measured using the subject of examination, in the compact OCT system described in item 7. (Item 9) The miniature OCT system according to item 8, wherein the miniature OCT system is configured to determine a change in thickness when two thickness measurements produce two thickness values ​​that differ by more than 50 μm. (Item 10) The repeatability is based on measurements performed within 1 minute and determined with a 95% confidence interval, as described in item 8 of the compact OCT system. (Item 11) The miniature OCT system according to item 8, wherein the reproducibility is within 25 μm, and the reproducibility represents the variation in measurements performed on the retina by one individual within a predetermined period under a set of conditions. (Item 12) The aforementioned predetermined period is at least two months, as described in item 11 for the compact OCT system. (Item 13) The compact OCT system according to item 11, further comprising an inspection device that provides an inspection material having multiple reflective surfaces. (Item 14) The miniature OCT system according to item 1, wherein the thickness is measured faster than the characteristic frequency of the movement of the miniature OCT system relative to the eye, and the movement is selected from the group consisting of movement, eye movements, and tremors related to a patient holding the OCT system in their hand. (Item 15) The miniature OCT system described in item 14 is configured to perform measurements at frequencies within the range defined by any two of the following: approximately 0.1 seconds (10 Hz), 0.02 seconds (50 Hz), 0.01 seconds (100 Hz), and 0.002 seconds (500 Hz). (Item 16) The small-sized OCT system according to item 1, wherein the light source, the plurality of optical elements, the detector, and the circuit are configured to be held in front of the eye with the detector at about 200 mm or less from the eye. (Item 17) The small-sized OCT system according to item 1, further comprising a visual target for the patient to align the light beam with the eye socket, and the visual target includes one or more of the light beam or light from a light-emitting diode. (Item 18) The small-sized OCT system according to item 1, wherein the light source includes a vertical cavity surface emitting laser (VCSEL) configured to vary the emission wavelength of the light beam over a range of about 5 to 10 nm. (Item 19) The small-sized OCT system according to item 18, wherein the VCSEL has a defined maximum rated range of wavelength variation. (Item 20) The small-sized OCT system according to item 19, wherein the circuit is configured to drive the VCSEL at least about 1 nm beyond the defined maximum range of the wavelength variation, and optionally within a range of about 1 nm to 5 nm beyond the defined maximum range of the wavelength variation. (Item 21) The small-sized OCT system according to item 19, wherein the circuit drives the VSCEL above the maximum value of the rated wavelength range for each of a plurality of measurements, and delays the first measurement from the second measurement by an amount within a range of about 1 millisecond ("ms") to about 100 milliseconds, optionally within a range of about 5 milliseconds to about 20 milliseconds, to prevent overheating of the VSCEL. (Item 22) The small-sized OCT system according to item 19, wherein the circuit is configured to drive the VCSEL above the maximum value of the rated wavelength range using a drive current having a waveform, the waveform having a first portion above the maximum rated current of the VCSEL and a second portion below the maximum rated current of the VCSEL, and the first portion comprising about 50 percent or less of the duration of the waveform to prevent overheating of the VCSEL. (Item 23) The circuit is configured to sweep the emission wavelength over a range of wavelengths with a sweep frequency, and the circuit is configured to determine the thickness in response to the frequency of the interference signal, the miniaturized OCT system according to item 1. (Item 24) The sweep frequency is within a range of about 50 Hz to about 10 KHz, optionally within a range of about 100 Hz to about 5 kHz or about 1 kHz to about 5 KHz, the miniaturized OCT system according to item 23. (Item 25) The sweep frequency is faster than the tremor of the user's eye or the tremor of the user's hand, the miniaturized OCT system according to item 23. (Item 26) The circuit is configured to heat the light source to change the wavelength, the miniaturized OCT system according to item 1. (Item 27) The plurality of optical elements are arranged to provide a reference optical path and a measurement optical path, and the interference signal is caused by the interference of light along the reference optical path and the measurement optical path, the miniaturized OCT system according to item 1. (Item 28) The plurality of optical elements are arranged to provide a reference optical path and a measurement optical path, and the interference signal is caused by the interference of light from the reference optical path and light from the measurement optical path, the miniaturized OCT system according to item 1. (Item 29) The plurality of optical elements are arranged to provide a measurement optical path, and the interference signal is caused by the interference of light from the layer of the retina along the measurement optical path, optionally without a reference optical path, the miniaturized OCT system according to item 1. (Item 30) The circuit includes a processor configured to convert the interference signal into an intensity profile of light reflected along the optical path of the beam directed into the eye, and to determine the thickness of the retina in response to the intensity profile, the miniaturized OCT system according to item 1. (Item 31) The miniature OCT system according to item 30, wherein the intensity profile comprises a plurality of reflection peaks, and the processor comprises instructions for determining the thickness in response to the plurality of reflection peaks. (Item 32) The compact OCT system according to item 30, wherein the processor comprises instructions for determining the intensity profile in response to the frequency of the interference signal, and optionally the intensity profile is determined using a fast Fourier transform of the interference signal measured using the detector. (Item 33) The miniature OCT system according to item 30, wherein the frequency of the interference signal corresponds to the separation distance of the retinal layers and the rate of change of the wavelength of the light source. (Item 34) The miniature OCT system according to item 30, wherein the frequency of the interference signal corresponds to the separation distance of the retinal layers and the rate of change of the wavelength of the beam emitted from the light source. (Item 35) The compact OCT system according to item 1, further comprising a visual target for aligning the tomography system with the orbit, wherein the visual target comprises one or more of the light beam, a target defined using a light-emitting diode, or a VCSEL. (Item 36) The compact OCT system according to item 1, wherein the light source comprises a first VCSEL and a second VCSEL, and the light beam comprises light from the first VSCEL and the second VSCEL. (Item 37) The circuit is configured to drive the first VCSEL and the second VCSEL sequentially using similar sweep frequencies to sweep a first wavelength of light from the first VSCEL and a second wavelength of light from the second VSCEL at similar speeds, wherein optionally the similar sweep frequencies and similar speeds of the first VSCEL and the second VSCEL are within 5% of each other, optionally within 1% of each other, in the compact OCT system according to item 36. (Item 38) The miniature OCT system according to item 36, wherein the circuit is configured to turn on the first VSCEL when the second VSCEL is off, and to turn on the second VSCEL when the first VSCEL is off, thereby preventing temporal overlap of light from the first VSCEL and the second VSCEL, and the second VSCEL is configured to turn on when the first VSCEL is turned off and emit light having a wavelength within approximately 0.1 nm of the light from the first VSCEL. (Item 39) The compact OCT system described in item 36 further comprises one or more beam splitters or optical fibers for coupling light from the first VSCEL. (Item 40) A miniature OCT system according to item 1, further comprising a housing for supporting the light source, the optical element, the detector, and the circuit, wherein the housing is configured to be held in the user's hand in front of the eye to direct the light beam into the eye. (Item 41) The small OCT system according to item 40, wherein the housing has a cylindrical shape with multiple indentations on a curved surface to facilitate gripping. (Item 42) The miniature OCT system according to item 40, further comprising a sensor for measuring an eye measured in response to the orientation of the housing. (Item 43) A miniature OCT system according to item 40, further comprising an occlusion structure for occluding one eye while the other eye is being measured, wherein the occlusion structure is coupled to the housing and the sensor for determining which eye is being measured. (Item 44) The miniature OCT system according to item 40, wherein the housing comprises a main body and a lid rotatably attached to the main body, the lid being configured to rotate around the main body when in the open position. (Item 45) The miniature OCT system according to item 40, further comprising a battery, wherein the battery is located further away from the detector than the light source. (Item 46) A miniature OCT system according to item 45, further comprising a docking station, the docking station receiving the housing and charging the battery contained within the housing in order to supply power to the light source and the circuit, the docking station comprising a wireless communication circuit for transmitting the thickness to a remote server, and optionally, the wireless communication circuit comprising a Global Systems for Mobile Communications (GSM®), third-generation (3G), or fourth-generation (4G) module. (Item 47) The miniature OCT system described in item 1, wherein the circuit is configured to receive or transmit data through a communication network. (Item 48) The aforementioned communication network includes the Internet, a cellular network, or a short-range communication network, as described in item 1, for the compact OCT system. (Item 49) The miniature OCT system is a miniature OCT system according to any one of items 1 to 48, having a mass in the range of approximately 50 grams to approximately 500 grams, and optionally in the range of approximately 100 grams to approximately 400 grams. (Item 50) The aforementioned compact OCT system is a compact OCT system according to any one of items 1 to 49, having a maximum traverse distance within a range of approximately 10 mm to approximately 100 mm, or optionally, within a range of approximately 25 mm to approximately 70 mm. (Item 51) A housing, wherein the light source, the detector, the circuit, and the optical element are contained within the housing, An optical fiber coupled to the light source and the detector, wherein the optical fiber extends from the miniature OCT system, Alignment structure coupled to the distal end of the optical fiber so as to align the light beam with the eye and direct the light beam toward the eye A compact OCT system described in any one of items 1 to 50, further comprising the features described in item 1 to 50. (Item 52) A method for measuring the thickness of a patient's retina using a small OCT system, wherein the method is: The thickness of the retina is measured repeatedly, thereby performing multiple measurements at multiple times, Based on the above multiple measurements, the change in thickness within the range of approximately 30 μm to approximately 70 μm is detected. Includes, The aforementioned compact OCT system has an axial resolution in the range of approximately 70 μm to approximately 150 μm. (Item 53) The thickness is measured using a wavelength swept within a range of approximately 5 nm to 10 nm, as described in item 52. (Item 54) The method according to item 52, wherein the repeated measurement includes performing a first measurement within 24 hours of an ophthalmologist's visit based on a second OCT system having a lower resolution value than the miniature OCT system, adjusting the thickness measured using the miniature OCT system, and performing a second measurement within a time range of 1 to 20 days after the first measurement. (Item 55) The repeated measurement described above is the method described in item 52, which involves taking one measurement daily over several days in a range of approximately 5 to 20 days. (Item 56) The method described in item 52, wherein the aforementioned multiple time periods are separated from each other by at least one day and no more than 20 days. (Item 57) The method according to item 52, wherein the aforementioned change in thickness is detected with at least a 95% confidence interval. (Item 58) A compact OCT system for measuring the thickness of an object, wherein the compact OCT system is Detector and A light source configured to generate a light beam having a variable wavelength, Multiple optical elements are coupled to the light source so as to direct the beam into the object and generate an interference signal on a detector, The detector and the circuit coupled to the light source Equipped with, The circuit is a compact OCT system that varies the wavelength and determines the thickness in response to the interference signal. (Item 59) A compact OCT system or method according to any one of items 1 to 58, further comprising a mirror, a plurality of mirrors, a gimbal, a lens, a galvanometer, an acousto-optic modulator, an electro-optic modulator, a translation optical element, an optical element that translates across the light beam, a deformable mirror, and an xy translation stage, wherein the system further comprises a scanning optical element. (Item 60) A miniature OCT system or method according to any one of items 1 to 59, further comprising a visual camera device. (Item 61) The miniature OCT system or method according to item 60, wherein the visual camera device is configured to acquire multiple images of the target eye. (Item 62) The aforementioned multiple images of the target eye are used to determine whether and by how much the target eye has moved between subsequent OCT measurements, according to the miniature OCT system or method described in item 61. (Item 63) A compact OCT system or method according to any one of items 1 to 62, further comprising a fundus camera device. (Item 64) The miniature OCT system or method according to item 63, wherein the fundus camera is configured to acquire multiple images of the fundus of the eye under consideration. (Item 65) The aforementioned multiple images of the fundus of the eye in question are used to determine whether and by how much the eye in question has moved between subsequent OCT measurements, according to item 64 of the miniature OCT system or method.

[0010] (Citation by reference) All publications, patents, and patent applications described herein are incorporated herein by reference to the same extent as each individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawing]

[0011] Novel features of the present invention are described in detail in the appended claims. A further understanding of the features and advantages of the present invention will be obtained by referring to the following embodiments for carrying out the invention, which describe illustrative embodiments in which the principles of the present invention are utilized, and the accompanying drawings.

[0012] [Figure 1] Figure 1 shows a simplified diagram of the human eye.

[0013] [Figure 2] Figure 2 shows schematic diagrams of systems, in several embodiments, that allow a patient to measure retinal thickness (RT) at multiple points in time and communicate the results.

[0014] [Figure 3A] Figure 3A shows several embodiments of a handheld optical coherence tomography (OCT) device that utilizes Bluetooth® communication.

[0015] [Figure 3B] Figure 3B shows several embodiments of a handheld OCT device utilizing Global Systems for Mobile Communications (GSM®).

[0016] [Figure 4] Figure 4 shows schematic diagrams of the information flow within a handheld OCT system in several embodiments.

[0017] [Figure 5] Figure 5 shows schematic diagrams of sweep source optical coherence tomography (SS-OCT) devices according to several embodiments.

[0018] [Figure 6A] Figure 6A shows schematic diagrams of SS-OCT devices lacking a reference mirror, according to several embodiments.

[0019] [Figure 6B] Figure 6B shows the wavelength ranges over which vertical cavity surface-emitting lasers (VCSELs) operate in SS-OCT devices lacking a reference mirror, according to several embodiments.

[0020] [Figure 7A] Figure 7A shows schematic diagrams of SS-OCT devices that utilize an external cavity according to several embodiments.

[0021] [Figure 7B] Figure 7B shows the wavelength ranges in which the VCSEL operates in an SS-OCT device lacking a reference mirror, according to several embodiments.

[0022] [Figure 7C] Figure 7C illustrates how the use of an external cavity mirror can shift the OCT peak to a higher optical frequency compared to the frequency of the OCT peak in the absence of the external cavity mirror.

[0023] [Figure 8A] Figure 8A shows a schematic diagram of an SS-OCT device utilizing two VCSELs and lacking a reference mirror at a first specific time point, according to several embodiments.

[0024] [Figure 8B] Figure 8B shows a schematic diagram of an SS-OCT device utilizing two VCSELs and lacking a reference mirror at a second specific point in time, according to several embodiments.

[0025] [Figure 8C]Figure 8C shows the wavelength ranges in which VCSELs operate in an SS-OCT device that utilizes two VCSELs and lacks a reference mirror, according to several embodiments.

[0026] [Figure 9] Figure 9 shows the operation of a VCSEL exceeding its maximum current rating in several embodiments.

[0027] [Figure 10A] Figure 10A shows a graphical representation of the axial resolution.

[0028] [Figure 10B] Figure 10B shows a graphical representation of repeatability and reproducibility.

[0029] [Figure 10C] Figure 10C shows a graphical representation of repeatability and reproducibility associated with RT measurements in retinas that do not exhibit RT changes.

[0030] [Figure 10D] Figure 10D shows a graphical representation of repeatability and reproducibility associated with RT measurements of the retina exhibiting changes in RT.

[0031] [Figure 11] Figure 11 is a flowchart illustrating a method for repeatedly measuring the patient's RT over time and paying attention to changes that may indicate adverse outcomes.

[0032] [Figure 12] Figure 12 shows a flowchart illustrating how to determine RT from measurements using a handheld OCT device.

[0033] [Figure 13] Figure 13 shows an exemplary digital processing device that is programmed or otherwise configured to determine RT or RLT.

[0034] [Figure 14]Figure 14 shows the optical configuration for determining the detection limits of an SS-OCT system using a single VCSEL and without a reference arm.

[0035] [Figure 15] Figure 15 shows the oscilloscope signals at two different time points when the VCSEL is driven outside its rated operating range.

[0036] [Figure 16] Figure 16 shows the oscilloscope signals for two different configurations of the optical setup.

[0037] [Figure 17] Figure 17 shows a signal processing method for extracting the vibration frequencies of an interference signal generated using an SS-OCT system that utilizes a single VCSEL and does not use a reference arm.

[0038] [Figure 18] Figure 18 shows the results of a study to determine the reproducibility of extracting the vibration frequencies of interference signals generated using a single VCSEL and an SS-OCT system without a reference arm.

[0039] [Figure 19] Figure 19 shows the mean and 95% confidence intervals of frequencies obtained during a study to determine the reproducibility of extracting the frequencies of vibrations of interference signals generated using a single VCSEL and an SS-OCT system without a reference arm.

[0040] [Figure 20A] Figure 20A shows a schematic diagram of a handheld OCT system with an eye adapter.

[0041] [Figure 20B] Figure 20B shows a handheld OCT system adapted for measuring either the right or left eye.

[0042] [Figure 20C] Figure 20C shows a handheld OCT system with indicator lights and a communication adapter.

[0043] [Figure 20D] Figure 20D shows a handheld OCT positioned close to the eye to provide OCT measurements.

[0044] [Figure 21] Figure 21 shows a calibration kit for a handheld OCT device.

[0045] [Figure 22] Figure 22 shows schematic diagrams of SS-OCT devices utilizing a scanning mechanism according to several embodiments.

[0046] [Figure 23A] Figure 23A shows schematic diagrams of scanning mechanisms according to several embodiments.

[0047] [Figure 23B] Figure 23B shows arrays of retinal layer thickness measurement sites according to several embodiments.

[0048] [Figure 24] Figure 24 shows schematic diagrams of SS-OCT devices utilizing a scanning mechanism and one or more cameras according to several embodiments.

[0049] [Figure 25] Figure 25 shows methods for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to several embodiments.

[0050] [Figure 26] Figure 26 shows schematic diagrams of SS-OCT devices incorporating a visual function measurement device according to several embodiments.

[0051] [Figure 27]Figures 27A and 27B show background visual cues according to several embodiments.

[0052] [Figure 28] Figures 28A and 28B show the configuration of a handheld monocular OCT system according to several embodiments.

[0053] [Figure 29] Figures 29A, 29B, and 29C show exemplary configurations of handheld binocular OCT systems according to several embodiments.

[0054] [Figure 30] Figure 30 shows the configuration of an exemplary handheld binocular OCT system according to several embodiments.

[0055] [Figure 31A] Figure 31A shows a handheld binocular OCT system, according to several embodiments, directed to measure the left eye of a subject.

[0056] [Figure 31B] Figure 31B shows housings for handheld binocular OCT systems, oriented to measure the right eye of a subject, according to several embodiments.

[0057] [Figure 32A] Figure 32A shows a VCSEL coupled to a cooler to increase the range of wavelengths swept, according to several embodiments.

[0058] [Figure 32B] Figure 32B shows schematic diagrams of VCSELs coupled to thermoelectric coolers according to several embodiments.

[0059] [Figure 33A] Figure 33A shows a small SS-OCT system mounted on a support, according to several embodiments.

[0060] [Figure 33B] Figure 33B shows users using a small SS-OCT device mounted on a support, according to several embodiments.

[0061] [Figure 34] Figure 34 shows schematic diagrams of the optical system of an SS-OCT device incorporating a fixation target device and a fundus imaging device according to several embodiments.

[0062] [Figure 35] Figure 35 shows schematic diagrams of electronic circuit boards for controlling the optical system of the miniature SS-OCT system described herein, according to several embodiments.

[0063] [Figure 36] Figure 36 shows a schematic diagram of the optical system of an SS-OCT device incorporating an interferometer to enhance phase stability.

[0064] [Figure 37A] Figures 37A, 37B, and 37C show exemplary fundus images obtained using the systems and methods described herein. [Figure 37B] Figures 37A, 37B, and 37C show exemplary fundus images obtained using the systems and methods described herein. [Figure 37C] Figures 37A, 37B, and 37C show exemplary fundus images obtained using the systems and methods described herein.

[0065] [Figure 38] Figures 38A and 38B show the effect of resampling for chirp correction of the SS-OCT signal in the time domain.

[0066] [Figure 39] Figures 39A, 39B, and 39C show the frequency drift of uncorrected and chirp-corrected SS-OCT signals in the frequency domain.

[0067] [Figure 40A] Figures 40A, 40B, and 40C show exemplary phase drift of uncorrected SS-OCT signals associated with various noise sources. [Figure 40B] Figures 40A, 40B, and 40C show exemplary phase drift of uncorrected SS-OCT signals associated with various noise sources. [Figure 40C] Figures 40A, 40B, and 40C show exemplary phase drift of uncorrected SS-OCT signals associated with various noise sources.

[0068] [Figure 41] Figures 41A, 41B, 41C, and 41D show simulations of phase shift associated with patient movement.

[0069] [Figure 42] Figures 42A, 42B, 42C, and 42D show simulations of the effect of scan time A on errors arising from phase shift associated with patient movement.

[0070] [Figure 43A] Figures 43A and 43B show the amplitude of typical patient movement. [Figure 43B] Figures 43A and 43B show the amplitude of typical patient movement. [Modes for carrying out the invention]

[0071] While various embodiments of the present invention are shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided only as examples. Numerous modifications, alterations, and substitutions can be conceived by those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be employed.

[0072] The compact OCT systems disclosed herein are highly suitable for use in conjunction with many previous clinical examinations, such as measuring retinal thickness. In some cases, the OCT system is used by the patient or by the healthcare provider. In many cases, the patient can align themselves with the system, while another user can align the patient with the system and perform the measurement. In some embodiments, the OCT system is integrated with previous software and systems to provide additional information to the healthcare provider and can provide alerts in response to changes in retinal thickness. Alerts are sent to the patient, caregiver, and healthcare provider when corrective actions should be taken, such as a change in medication, dosage, or medication reminder.

[0073] As used herein, the term “retinal thickness (RT)” refers to the thickness of the retina between layers used to assess the thickness of a patient’s retina. RT may, for example, correspond to the thickness of the retina between the anterior surface and the outer limiting membrane.

[0074] As used herein, the term “retinal layer thickness (RLT)” refers to the thickness of one or more optically detectable layers of the retina. The optically detectable layers of the retina may include, for example, the thickness of the retina extending between the outer limiting membrane and the retinal pigment epithelium.

[0075] As used herein, the term “high resolution” refers to a measurement system capable of optically resolving structures that have at least one linear dimension smaller than structures that can be resolved by a lower resolution measurement system.

[0076] Figure 1 shows a simplified diagram of the human eye. Light enters the eye through the cornea 10. The iris 20 controls the amount of light allowed to pass through by varying the size of the pupil 25, which allows light to proceed to the lens 30. The anterior chamber 40 contains aqueous humor 45, which determines the intraocular pressure (IOP). The lens 30 focuses the light for image formation. The focal properties of the lens are controlled by muscles that reshape the lens. The focused light passes through the vitreous cavity 50, which is filled with vitreous fluid 55. The vitreous fluid maintains the overall shape and structure of the eye. The light then travels toward the retina 60, which has a photosensitive area. In particular, the macula 65 is the area of ​​the retina responsible for receiving light at the center of the visual plane. Within the macula, the fovea 70 is the area of ​​the retina most sensitive to light. The light traveling toward the retina generates electrical signals that are passed to the optic nerve 80 and then to the brain for processing.

[0077] Several disorders can lead to a reduction in the optical performance of the eye. In some cases, intraocular pressure (IOP) is either too high or too low. This can be caused, for example, by an excessively high or low production rate of aqueous humor in the anterior chamber. In other cases, the retina is either too thin or too thick. This can result, for example, from the accumulation of fluid within the retina. Diseases associated with abnormal retinal thickness (RT) include, for example, glaucoma and macular edema. In some cases, the healthy range for RT is 175 μm to 225 μm. Generally, abnormalities in either IOP or RT indicate the presence of many ophthalmic diseases. In addition, IOP or RT fluctuate in response to ophthalmic treatment or other procedures. Therefore, it is desirable to have means to measure IOP and / or RT for the diagnosis of ophthalmic diseases and to assess the effectiveness of treatment for a given patient. In some cases, it is desirable to measure the thickness of one or more retinal layers, for example, the thickness of multiple layers.

[0078] The systems and methods disclosed herein relate to the use of optical coherence tomography (OCT) for measuring RT or RLT at multiple time points in time. For example, a patient measures their RT or RLT at multiple time points to track the progression of an ophthalmic disease such as glaucoma or macular edema over time. In another embodiment, a patient measures their RT or RLT at multiple time points to track their response to medication or other treatments. In some cases, the system generates an alert when one or more recent measurements of RT or RLT deviate significantly from previous measurements. In other cases, the system alerts the patient or the patient's physician to the change. In some cases, this information is used to schedule follow-up appointments between the patient and the physician, for example, to try a treatment for the ophthalmic disease, to discontinue a prescribed treatment, or to perform additional tests.

[0079] Figure 2 shows a schematic diagram of a system, according to several embodiments, that enables a patient to measure RT or RLT at multiple time points and communicate the results. The patient looks into a handheld OCT device 100 to obtain RT or RLT measurements. In some embodiments, the handheld OCT device comprises an optical system 102, electronic equipment 104 for controlling and communicating with the optical system, a battery 106, and a transmitter 108. In some cases, the transmitter is a wired transmitter. In other cases, the transmitter is a wireless transmitter. In some cases, the handheld OCT device communicates the results to a mobile patient device 120 on the patient's smartphone or other portable electronic device via a wireless communication channel 110. In some cases, the wireless communication is via Bluetooth® communication. In some embodiments, the wireless communication is via Wi-Fi communication. In other embodiments, the wireless communication is via any other wireless communication known to those skilled in the art.

[0080] In some cases, the result is a fully processed measurement of RT. In other cases, all processing of the OCT data is performed on a handheld OCT device. For example, in some embodiments, the handheld OCT device includes hardware or software elements that enable the OCT optical waveform to be converted into an electronic representation. In some cases, the handheld OCT device further includes hardware or software elements that enable processing of the electronic representation, for example, extracting the measurement of RT.

[0081] In some cases, the result is an electronic representation of the raw optical waveform obtained from the OCT measurement. For example, in some embodiments, a handheld OCT device includes hardware or software elements that enable the OCT optical waveform to be converted into an electronic representation. In some cases, these electronic representations are then passed to a mobile patient device for further processing, such as extracting RT measurements.

[0082] In some embodiments, the patient receives the results and analysis of RT or RLT measurements on a patient mobile app. In some embodiments, the results include an alert 122 that warns the patient if the measurement result is normal or outside the healthy range. In some embodiments, the results also include a display of the measured value 124. For example, in some cases, an RT or RLT measurement produces a result of 257 μm. In some cases, this result is normal or outside the healthy range. This causes the system to generate an alert and display the 257 μm measured value on the patient mobile app. In some embodiments, the results also include a chart 126 showing the patient's RT or RLT history over multiple points in time.

[0083] In some cases, a patient mobile device communicates measurement results to a cloud-based or other network-based storage and communication system 140 via a communication means 130. In some embodiments, the communication means is a wired communication means. In some embodiments, the communication means is a wireless communication means. In some cases, the wireless communication is via Wi-Fi communication. In other cases, the wireless communication is via a cellular network. In yet other cases, the wireless communication is via any other wireless communication known to those skilled in the art. In specific embodiments, the wireless communication means is configured to enable transmission to or reception from a cloud-based or other network-based storage and communication system.

[0084] Once stored in the cloud, in specific embodiments, the results are then transmitted to other devices. In some cases, the results are transmitted via a first communication channel 132 to a patient device 150 on the patient's computer, tablet, or other electronic device. In some embodiments, the results are transmitted via a second communication channel 134 to a physician device 160 on the physician's computer, tablet, or other electronic device. In some cases, the results are transmitted via a third communication channel 136 to an analysis device 170 on another user's computer, tablet, or other electronic device. In some embodiments, the results are transmitted via a fourth communication channel 138 to a patient management system or hospital management system 180. In some cases, each of the devices has appropriate software instructions to perform the relevant functions as described herein.

[0085] In specific embodiments, the first communication channel is either a wired or wireless communication channel. In some cases, the communication is via Ethernet®. In other cases, the communication is via a local area network (LAN) or a wide area network (WAN). In yet another case, the communication is via Wi-Fi. In yet another case, the communication is via any other wired or wireless communication known to those skilled in the art. In some embodiments, the first communication channel is configured to allow transmission to or reception from a cloud-based or other network-based storage and communication system. In some cases, the first communication channel is configured to allow reception only from a cloud-based or other network-based storage and communication system.

[0086] In some cases, the second communication channel is a wired or wireless communication channel. In some cases, the communication is via Ethernet®. In specific embodiments, the communication is via a local area network (LAN) or a wide area network (WAN). In other embodiments, the communication is via Wi-Fi. In yet another embodiment, the communication is via any other wired or wireless communication known to those skilled in the art. In some cases, the second communication channel is configured to allow transmission to or reception from a cloud-based or other network-based storage and communication system. In some embodiments, the second communication channel is configured to allow reception only from a cloud-based or other network-based storage and communication system.

[0087] In specific cases, the third communication channel is either a wired or wireless communication channel. In some cases, the communication is via Ethernet®. In other cases, the communication is via a local area network (LAN) or a wide area network (WAN). In yet another case, the communication is via Wi-Fi. In yet another case, the communication is via any other wired or wireless communication known to those skilled in the art. In some embodiments, the third communication channel is configured to enable transmission to or reception from a cloud-based or other network-based storage and communication system. In some cases, the third communication channel is configured to enable reception only from a cloud-based or other network-based storage and communication system.

[0088] In some embodiments, the fourth communication channel is either a wired or wireless communication channel. In some cases, the communication is via Ethernet®. In other cases, the communication is via a local area network (LAN) or a wide area network (WAN). In yet another case, the communication is via Wi-Fi. In yet another case, the communication is via any other wired or wireless communication known to those skilled in the art. In some cases, the fourth communication channel is configured to allow transmission to or reception from a cloud-based or other network-based storage and communication system. In other cases, the fourth communication channel is configured to allow reception only from a cloud-based or other network-based storage and communication system.

[0089] The determination of RT or RLT can be performed in many locations. For example, the determination of RT or RLT is performed on a handheld OCT device. In some cases, the determination of RT or RLT is performed in the vicinity of the handheld OCT device, such as by a smartphone or other portable electronic device. In some embodiments, the determination of RT or RLT is performed on a cloud-based storage and communication system. In one example, the handheld OCT device is configured to compress the measurement data and transmit the compressed measurement data to the cloud-based storage and communication system.

[0090] In some embodiments, the patient receives the results and analysis of an RT or RLT measurement on a patient device 150. In some cases, the results include an alert 152 that warns the patient if the measurement result is normal or outside the healthy range. In some cases, the results also include a display of the measurement 154. For example, in some cases, an RT or RLT measurement produces a result of 257 μm. This result is normal or outside the healthy range. In some cases, this causes the system to generate an alert and display the 257 μm measurement on the patient app. In specific cases, the results also include a chart 156 showing the patient's RT or RLT history over several points in time. In some cases, the patient device also displays instructions 158 for the patient to follow. In some cases, the instructions instruct the patient to visit their doctor. In some embodiments, the instructions include the patient's name, the date of the most recent RT or RLT measurement, and the next scheduled visit to that doctor. In other cases, the instructions include more information. In yet another case, the instructions include less information.

[0091] In some embodiments, the patient's physician receives the results and analysis of RT or RLT measurements on the physician device 160. In some cases, the results include an alert 162 that warns the physician if the measurement result is normal or outside the healthy range. In some cases, the results also include an alert 164 that informs the physician if the patient's measurement is normal or outside the healthy range. In some embodiments, the alert includes a suggestion for the physician to call the patient, schedule an appointment, or provide medical assistance. In some embodiments, the results also include a display 166 showing the most recent and historical measurements for each of the physician's patients. For example, in one case, an RT or RLT measurement produces a result of 257 μm. This result is normal or outside the healthy range. In some cases, this causes the system to generate an alert and display the 257 μm measurement on the physician app. In specific cases, the physician device also displays contact and history information 168 for each of the physician's patients.

[0092] In some embodiments, the other user receives the results and analysis of RT or RLT measurements on the analysis device 170. In one case, the other user is a researcher investigating the effectiveness of a new form of treatment. In other cases, the other user is an auditor monitoring outcomes at a particular physician or care facility. To protect patient privacy, in some cases the analysis device is restricted to receiving only a subset of information about a given patient. For example, the subset is restricted so as not to include any personally identifiable information about a given patient. In some cases, the results include an alert 172 warning that a large number of abnormal or unhealthy measurements have been taken within a specific period. In some cases, the results include one or more graphical representations 174 of the measurements across a population of patients.

[0093] In some cases, the results and analysis on the analysis device include disease information such as a physician-confirmed diagnosis. In some cases, the results and analysis include anonymized patient data such as age, sex, genetic information, information about the patient's environment, smoking history, and other diseases the patient has had. In some cases, the results and analysis include anonymized treatment plans for the patient, such as a list of prescribed medications and treatment history. In some cases, the results and analysis include measurement results such as RT or RLT measurement results, visual function tests, or patient compliance with the treatment process. In some cases, the results and analysis include data from electronic medical records. In some cases, the results and analysis include diagnostic information from the patient's visit to the healthcare provider, such as OCT scan results obtained by the patient's healthcare provider.

[0094] In some embodiments, the patient's clinical, hospital, or other healthcare provider receives the results and analysis of RT or RLT measurements on a patient management system or hospital management system 180. In some cases, the system includes the patient's electronic medical record. In some cases, the results and analysis provide the patient's healthcare provider with data that enables the provider to update the treatment plan for the patient. In some cases, the results and analysis enable the provider to decide to call the patient for an early outpatient consultation. In some cases, the results and analysis enable the provider to decide to postpone the outpatient consultation.

[0095] In some embodiments, one or more of the patient device, physician device, and analysis device include a software app that provides instructions for performing the functions of the patient device, physician device, or analysis device, as described herein.

[0096] Figure 3A shows a handheld OCT device utilizing short-range wireless communication in several embodiments. In some embodiments, the handheld OCT device 100 comprises an optical system 102, electronic equipment 104 for controlling and communicating with the optical system, a battery 106, and a wireless transmitter 108. In some cases, the wireless transmitter is a Bluetooth® transmitter. In some cases, results from one or more RT or RLT measurements are stored on the handheld OCT device until an authorized user, such as the patient or another person designated by the patient, opens a patient mobile device on a smartphone or other portable electronic device. Once opened, the patient mobile device establishes wireless communication with the handheld OCT device. In some cases, the communication is via a Bluetooth® wireless communication channel 110. In some cases, the handheld OCT device communicates the results via the Bluetooth® channel to a mobile patient device 120 on the patient's smartphone or other portable electronic device.

[0097] In some cases, the results include an alert 122 that warns the patient if the measurement result is normal or outside the healthy range. In specific embodiments, the results also include a display of the measured value 124. For example, an RT or RLT measurement may, in some cases, produce a result of 257 μm. This result is normal or outside the healthy range. In some cases, this causes the system to generate an alert and display the 257 μm measured value on the patient's mobile app. In specific embodiments, the results also include a chart 126 showing the patient's RT or RLT history over several points in time.

[0098] In some cases, the patient's mobile device communicates the measurement results to a cloud-based or other network-based storage and communication system 140 via wireless communication means 130. In some cases, the wireless communication is Wi-Fi communication. In other cases, the Wi-Fi communication is via a secure Wi-Fi channel. In yet another case, the wireless communication is via a cellular network. In a specific embodiment, the cellular network is a secure cellular network. In another embodiment, the transmitted information is encrypted. In some cases, the communication channel is configured to allow transmission to or reception from a cloud-based or other network-based storage and communication system. In some cases, the data is stored on the smartphone or other portable electronic device until the smartphone or other portable electronic device connects to a Wi-Fi or cellular network.

[0099] In some cases, the patient mobile device has a feature that notifies the patient or another person designated by the patient when an excessive amount of time has passed since the patient mobile device was last opened. For example, in some cases, this notification occurs because the patient has not obtained an RT or RLT measurement in the most recent time as required by the measurement schedule set by their physician or other healthcare provider. In other cases, the notification occurs because the handheld OCT device has stored an excessive amount of measurement results and the data needs to be transmitted to the patient's smartphone. In specific embodiments, the patient mobile device communicates with a cloud-based or other network-based storage and communication system to display a complete set of patient data.

[0100] Figure 3B shows several embodiments of a handheld OCT device capable of communicating directly with a cloud-based storage and communication system without relying on a user device such as a smartphone. In some embodiments, the handheld OCT device 100 comprises an optical system 102, electronic equipment 104 for controlling and communicating with the optical system, a battery 106, and a wireless transmitter 108. In some cases, the wireless transmitter is a GSM® transmitter. In some cases, results from one or more RT or RLT measurements are stored on the handheld OCT device. In some cases, the GSM® transmitter establishes wireless communication with a cloud-based or other network-based storage and communication system 140 via a wireless communication channel 114. In specific cases, the wireless communication is via a GSM® wireless communication channel. In other embodiments, the system utilizes a third-generation (3G) or fourth-generation (4G) mobile communication standard. In such cases, the wireless communication is via a 3G or 4G communication channel.

[0101] In specific embodiments, the patient mobile device 120 receives measurement results from a cloud-based or other network-based storage and communication system 140 via wireless communication means 130. In some cases, the wireless communication is via Wi-Fi communication. In some cases, the Wi-Fi communication is via a secure Wi-Fi channel. In other cases, the wireless communication is via a cellular network. In some cases, the cellular network is a secure cellular network. In specific cases, the transmitted information is encrypted. In some embodiments, the communication channel is configured to allow transmission to or reception from a cloud-based or other network-based storage and communication system.

[0102] When retrieved from a cloud-based or other network-based storage and communication system, the results of an RT or RLT measurement are, in some cases, visible on a patient mobile app. In some cases, the results include an alert 122 that warns the patient if the measurement result is normal or outside the healthy range. In some cases, the results also include a display of the measurement 124. For example, in some cases, an RT or RLT measurement produces a result of 257 μm. This result is normal or outside the healthy range. In a specific embodiment, this causes the system to generate an alert and display the 257 μm measurement on the patient mobile app. In some embodiments, the results also include a chart 126 showing the patient's RT or RLT history over multiple points in time.

[0103] In some cases, the patient mobile device has a feature that notifies the patient or another person designated by the patient when an excessive amount of time has passed since the patient mobile device was last opened. For example, in some cases, this notification occurs because the patient has not obtained an RT or RLT measurement in the most recent time as required by the measurement schedule set by their physician or other healthcare provider. In other cases, the notification occurs because the handheld OCT device has stored an excessive amount of measurement results and the data needs to be transmitted to the patient's smartphone. In specific embodiments, the patient mobile device communicates with a cloud-based or other network-based storage and communication system to display a complete set of patient data.

[0104] In some cases, a handheld OCT device comprises a short-range transmitter and a GSM®, 3G, or 4G transmitter. In some cases, the short-range transmitter is a Bluetooth® transmitter. In some cases, the handheld OCT device communicates directly with a patient mobile device on a smartphone or other portable electronic device via a Bluetooth® wireless communication channel. In some embodiments, the handheld OCT also communicates with a cloud-based or other network-based storage and communication system via a GSM®, 3G, or 4G wireless communication channel. In specific cases, the cloud-based system then communicates with the patient mobile device via Wi-Fi, cellular, or other wireless communication channels. Alternatively, the Bluetooth® transmitter is integrated into a docking station. In some cases, this allows the use of older devices for patients who lack a smartphone. In some cases, the docking station also includes means for charging the battery of the handheld OCT device.

[0105] In some cases, the handheld OCT devices in Figures 3A and 3B are configured to be held in close proximity to the eye. For example, in a specific embodiment, the device is configured to be held in front of the eye with a detector at a distance of 200 mm or less from the eye. In other embodiments, the device is configured to be held in front of the eye with a detector at a distance of 150 mm or less, 100 mm or less, or 50 mm or less from the eye. In specific cases, the handheld OCT device further comprises a housing for supporting a light source, optical elements, a detector, and circuitry. In some cases, the housing is configured to be held in the user's hand. In other cases, the user holds the device in front of their eye and directs the light beam into the eye. In some cases, the device includes a sensor for measuring which eye is being measured. For example, in a specific embodiment, the device includes an accelerometer or gyroscope for determining which eye is being measured in response to the orientation of the housing. The device optionally includes an occlusion structure coupled to the housing and a sensor for determining which eye is being measured. The occlusion structure occludes one eye while the other eye is being measured. In some cases, the device includes a visual target for aligning a light beam with a portion of the retina. For example, in specific embodiments, the device includes a visual target for aligning a light beam with the orbit. In some cases, the visual target is a light beam. In other cases, the visual target is a light-emitting diode. In other cases, the visual target is a vertical cavity surface-emitting laser (VCSEL). In yet another case, the visual target is any visual target known to those skilled in the art.

[0106] The optical components described herein can be miniaturized to provide handheld OCT devices with reduced physical size and mass, as will be understood by those skilled in the art.

[0107] In many embodiments, the handheld OCT devices in Figures 3A and 3B are small and light enough to be easily operated with one hand by the user. For example, in many embodiments, the device has a mass in the range of about 100 grams to about 500 grams. In many embodiments, the device has a mass in the range of about 200 grams to about 400 grams. In many embodiments, the device has a mass in the range of about 250 grams to about 350 grams. In specific embodiments, the device has a maximum traverse distance in the range of about 80 mm to about 160 mm. In specific embodiments, the device has a maximum traverse distance in the range of about 100 mm to about 140 mm. In specific embodiments, the device has a width in the range of about 110 mm to about 130 mm. In some embodiments, the maximum traverse distance is equal to the length. In some embodiments, the device has a width less than its length. In specific embodiments, the device has a width in the range of about 40 mm to about 80 mm. In specific embodiments, the device has a width in the range of about 50 mm to about 70 mm. In a specific embodiment, the device has a width in the range of approximately 55 mm to approximately 65 mm.

[0108] Figure 4 shows a schematic diagram of the information flow within a handheld OCT system according to several embodiments. In some embodiments, the handheld OCT device 400 further comprises a subsystem 402 for measuring RT or RLT and a device storage system 404. In some embodiments, the device storage system comprises any form of volatile or non-volatile memory, including, but not limited to, flash memory or random access memory (RAM). In some cases, the subsystem for measuring RT or RLT is communicatively coupled to the device storage system. In some cases, the handheld OCT device transmits measurement data to a smartphone or any other computing device 410. For example, in some cases, the smartphone or another handheld device further comprises a smartphone storage system 414 and launches a smartphone application 412.

[0109] In some cases, the computing device transmits patient data and measurement data to the patient device 420. In some embodiments, the smartphone device is communicatively coupled to a cloud-based or other network-based storage and communication system 430. In some cases, the cloud-based or other network-based storage system further comprises one of the following: a mobile application programming interface (API) 432, a patient device 434, a physician device 436, an analysis device 438, a measurement and treatment storage system 440, a patient data storage system 442, and an API 444 that interfaces with a patient management system or hospital management system.

[0110] In some cases, the mobile API is communicatively coupled to a smartphone application. In some embodiments, the mobile API is configured to send and receive measurement information (e.g., RT measurements) from the smartphone application. In some cases, the mobile API is configured to send patient data (e.g., identification information or demographic information) to the smartphone device but not to receive this information from the smartphone application. In some cases, this configuration is designed to reduce the possibility of compromising patient data. In some embodiments, the mobile API is configured to send measurement data and patient data to a patient device and to receive measurement data and patient data from the patient application. In some cases, the patient device is further configured to send measurement data and patient data to a patient and to receive measurement data and patient data from a patient.

[0111] In some cases, the mobile API is configured to send measurement data and patient data to a physician device and to receive measurement data and patient data from a physician app. In other cases, the mobile API is configured to send measurement data to a physician device and to receive measurement data from a physician device, but to request that the patient data first pass through a patient data storage system. In such cases, the patient data storage system is configured to send patient data to a physician device and to receive patient data from a physician app. In some embodiments, the patient data storage system is configured to send patient data to an API that interfaces with a patient management system or hospital management system and to receive patient data from an API that interfaces with a patient management system or hospital management system. In one example, the API that interfaces with a patient management system or hospital management system is configured to send patient data to a patient management system or hospital management system 480 and to receive patient data from a patient management system or hospital management system. In some cases, the physician device is further configured to send measurement data and patient data to a physician 450 and to receive measurement data and patient data from a physician.

[0112] In some cases, the mobile API is configured to send measurement data to an analysis app and to receive measurement data from the analysis app. In some embodiments, the analysis device is configured to send measurement data to the manufacturer or developer of the handheld OCT system 460. In some cases, the analysis device is configured to send anonymized patient data to the manufacturer or developer of the handheld OCT system. In some cases, the analysis device is configured to send a subset of measurement data to other parties 470. In some embodiments, the analysis device is configured to send anonymized patient data to other parties 470.

[0113] In some embodiments, cloud-based or other network-based memory and communication systems further include a measurement and therapeutic memory system. In one example, the measurement and therapeutic memory system is configured to send measurement data to one of the following: a mobile API, a patient app, a physician app, and an analytics app. In another example, the measurement and therapeutic memory system is configured to receive measurement data from one of the following: a mobile API, a patient app, a physician app, and an analytics app.

[0114] In addition to the patient management system or hospital information system, a cloud-based or other network-based storage and communication system is, in some cases, communicatively coupled to the local patient management system 482. In some embodiments, the local patient management system is configured to transmit patient data to a physician app.

[0115] A handheld OCT device can utilize any method for optical coherence tomography. In some cases, the handheld OCT device utilizes time-domain OCT. In some embodiments, the handheld OCT device utilizes frequency-domain OCT. In some cases, the handheld OCT device utilizes spatially encoded frequency-domain OCT. In other cases, the handheld OCT device utilizes time-coded frequency-domain OCT, also known as sweep-source OCT (SS-OCT).

[0116] Figure 5 shows schematic diagrams of the optical systems of a swept-source optical coherence tomography (SS-OCT) device according to several embodiments. In some cases, the optical system 102 comprises a light source 500, a beam splitter 510, a front-end optical system 520, a reference mirror 530, and a processing unit 540. In some embodiments, the processing unit further comprises a photodetector 542 and a signal processing module 544. Light from the light source strikes the beam splitter. Part of the light is directed along a reference arm to the reference mirror, and part of the light is directed to the front-end optical system and then to the sample 550. In some cases, the sample consists of an eye. In other cases, the sample consists of a retina. In some embodiments, the retina consists of several layers of tissue. In some cases, the layers of tissue consist of layers of photosensitive rods and cones 552, retinal pigment epithelium (RPE) 554, and choroid 556. In other cases, the tissue layers consist of the nerve fiber layer, ganglion cell layer, internal plexiform layer, internal granular layer, external plexiform layer, external granular layer, internal limiting membrane, external limiting membrane, and / or Bruch's membrane, among other layers of the retina. Light is reflected back to the device at each boundary of each layer. The light reflected from each boundary interferes with the light reflected from the reference mirror and the light reflected from any other boundary. The interference signal is detected by the photodetector. In some cases, light is reflected from the posterior surface of the rod and cone cell layer, the anterior surface of the rod and cone cell layer, the posterior surface of the internal limiting membrane, the anterior surface of the internal limiting membrane, the posterior surface of the choroid, and / or the anterior surface of the choroid. Light can be reflected from any surface of any other layer, such as the nerve fiber layer, ganglion cell layer, internal plexiform layer, internal granular layer, external plexiform layer, external granular layer, external limiting membrane, and / or retinal pigment epithelium. In some cases, the RLT corresponds to the thickness of any one of these retinal layers, or the thickness between any two such layers.

[0117] This process is repeated over a range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength, reaching a maximum value when the light reflected from one boundary and the light reflected from the reference mirror are in phase, or when the light reflected from one boundary is in phase with the light reflected from another boundary. This state is achieved at one or more specific wavelengths of light for each boundary and is characterized by one or more maximum values ​​of the interference signal. At other wavelengths, the interference signal exhibits either partial constructive or destructive interference. The interference signals at all wavelengths are compiled to form an interferogram 560. The interferogram undergoes a signal analysis procedure. In some cases, the interferogram undergoes a frequency analysis procedure, such as a Fast Fourier Transform (FFT), to form a spectrum 570. The spectrum has peaks corresponding to the interference signal associated with various retinal layer thicknesses. In some embodiments, SS-OCT utilizes a light source with a relatively long coherence length (typically exceeding several millimeters). In some cases, the amplitude of the interference signal decreases as the distance between the two retinal layers increases. In some cases, the location of the peak indicates the thickness of each layer of tissue.

[0118] In some cases, the light source comprises a laser source. In some embodiments, the laser source generates laser light having a tunable wavelength. In some cases, the laser source is scanned over a range of wavelengths to acquire an OCT signal. In some cases, the laser source can be rapidly scanned to enable rapid acquisition of an OCT signal. In some cases, the laser source comprises a vertical cavity surface-emitting laser (VCSEL). In some embodiments, the VCSEL is tuned by varying the current supplied to the VCSEL. In some cases, the VCSEL is continuously scanned across a range of wavelengths by continuously varying the current. In some cases, the VCSEL is periodically scanned across a range of wavelengths by periodically varying the current. In some embodiments, the VCSEL is supplied with a sinusoidally varying current to produce sinusoidally varying wavelengths.

[0119] In some embodiments, the VCSEL is a commercially available VCSEL. In some cases, the VCSEL is a VCSEL modified from a commercially available VCSEL based on the teachings described herein. In some cases, the VCSEL is a VCSEL obtained from manufacturers such as Phillips Photonics, Frankfurt Laser Company, Hamamatsu Corporation, New Focus, Power Technology, Avago Technologies, Masimo Semiconductor, Finisar, Oclaro, or any other manufacturer known to those skilled in the art.

[0120] In some cases, a VCSEL has a maximum recommended current for continuous or pulsed use. In some cases, the maximum continuous current rating limits the range of wavelengths that the VCSEL can sweep. For example, a VCSEL may be limited to continuous operating currents of 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, 9 mA, or 10 mA or less. In some embodiments, the wavelengths emitted by the VCSEL vary linearly with the operating current, with a proportionality constant of 0.3 nm / mA. In some cases, this limits the range of wavelengths that the VCSEL can sweep to 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, or 3.0 nm. In some embodiments, this limits the attainable axial resolution of a VCSEL-based SS-OCT device. Assuming a Gaussian spectrum from the light source, the attainable axial resolution is determined as follows:

number

[0121] Therefore, in some cases, the limited operating range of the VCSEL limits the achievable axial resolution. In some embodiments, for a VCSEL with a central operating wavelength of 850 nm, the achievable axial resolution is as good as 1,062 μm, 531 μm, 354 μm, 266 μm, 213 μm, 177 μm, 152 μm, 133 μm, 118 μm, or 106 μm for operating ranges of 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, and 3.0 nm, respectively. In some cases, VCSELs emit light intensities of 0.01mW, 0.025mW, 0.05mW, 0.1mW, 0.25mW, 0.5mW, 1mW, 2.5mW, 5mW, 10mW, 25mW, 50mW, 100mW, 250mW, 500mW, 1W, 2.5W, 5W, 10W, 25W, 50W, or 100W or less.

[0122] Table 1 shows the axial resolution for the corresponding wavelength range of the sweep source for a central operating wavelength of 850 nm. [Table 1]

[0123] Table 1 refers to a central wavelength of 850 nm, but those skilled in the art can construct compact OCT systems operating at different central wavelengths with similar sweep ranges and resolutions according to the disclosures provided herein. Furthermore, those skilled in the art can easily correct the above values ​​according to the refractive index of the retina, which is generally about 1.3 to 1.4.

[0124] In some cases, an additional VSCEL is used to extend the sweep wavelength range as described herein.

[0125] In some cases, the limited operating range of a VCSEL also limits its ability to extract information from the OCT signal due to a limited phase shift imparted by a limited optical path difference (OPD). The phase shift between the light reflected from the first interface and the light reflected from the second interface is determined by the following:

number

[0126] In some cases, it is useful to extract frequency information from the interference signal resulting from the interaction of light reflected from the first interface and light reflected from the second interface. To extract this information, it may be helpful to obtain the two signal periods of the interferogram, which corresponds to a phase shift of 4π. Thus, the minimum wavelength range Δλ of the VCSEL is determined by the following: min It should operate over time.

number

[0127] Therefore, in some cases, the limited operating range of a VCSEL limits its ability to acquire sufficient phase shift to extract frequency information from the interference signal. In some embodiments, with respect to a VCSEL with a central operating wavelength of 850 nm that forms an interference pattern between reflective interfaces separated by 150 μm in a medium with a refractive index of 1.3 similar to that of the retina, the minimum wavelength range is 3.7 nm. In some cases, this wavelength range typically exceeds the wavelength range emitted by a VCSEL operating within its maximum recommended current for continuous use. Therefore, in some cases, it is helpful to extend the wavelength range emitted by the VCSEL to generate sufficient phase shift.

[0128] The light source does not necessarily have to be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous radiation (ASE). In other cases, the light source is a superluminescent diode (SLD). In addition, in some embodiments, the light source comprises multiple light sources.

[0129] In some cases, the front-end optical system comprises optical elements such as lenses. In some embodiments, the front-end optical system comprises any reflective, refractional, or diffractive elements. In some cases, the front-end optical system comprises two or more reflective, refractional, or diffractive elements. In some cases, the front-end optical system comprises electro-optical, magneto-optical, acoustic-optical, or mechanical-optical devices. In some embodiments, the front-end optical system comprises any optical elements known to those skilled in the art.

[0130] In some embodiments, the front-end optical system includes scanning optical elements to allow the light source to be moved to different locations on the retina. In some cases, this allows multiple measurements to be taken to determine RT or RLT at different locations on the retina. In some cases, determining RT or RLT at different locations on the retina further allows the location of the orbit to be confirmed. In some embodiments, the scanning optical elements are selected from the group consisting of mirrors, multiple mirrors, gimbals, lenses, galvanometers, acoustic-optic modulators, electro-optic modulators, translation optical elements, optical elements that translate across a light beam, deformable mirrors, and xy translation stages. In some cases, the scanning optical elements consist of any scanning optical elements known to those skilled in the art.

[0131] In some cases, the device further comprises scanning optical elements as described herein.

[0132] Figure 6A shows a schematic diagram of the optical system of a sweep-source optical coherence tomography (SS-OCT) device lacking a reference mirror, according to several embodiments. In some cases, the optical system 102 comprises a VCSEL or other light source 600, a beam splitter 610, a front-end optical system 620, and a processing unit 640. In some embodiments, the processing unit further comprises a photodetector 642 and a signal processing module 644. Light from a broadband source collides with the beam splitter. The light is directed to the front-end optical system and then to the sample 650. The light is back-reflected by the device at each boundary of each layer. Light reflected from one layer boundary interferes with light reflected from another layer boundary. The interference signal is detected by the photodetector.

[0133] This process is repeated over a range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength, reaching a maximum value when light reflected from one boundary is in phase with light reflected from another boundary. This state is achieved at one or more specific wavelengths of light for each boundary and is characterized by one or more maximum values ​​of the interference signal. At other wavelengths, the interference signal exhibits either partial constructive or destructive interference. The interference signals at all wavelengths are compiled to form an interferogram. The interferogram undergoes a signal analysis procedure. In some cases, the interferogram undergoes a frequency analysis procedure, such as a Fast Fourier Transform (FFT), to form a spectrum. The spectrum has peaks corresponding to wavelengths associated with the maximum interference values ​​for each boundary. In some embodiments, SS-OCT utilizes a light source with a relatively long coherence length (typically exceeding several millimeters). In some cases, the amplitude of the interference signal decreases as the distance between the two retinal layers increases. In some cases, the position of the peaks indicates the thickness of each layer of tissue.

[0134] In some embodiments, the light source comprises a laser source. In some embodiments, the laser source generates laser light having a tunable wavelength. In some cases, the laser source is scanned across a wavelength range to acquire an OCT signal. In some embodiments, the laser source can be rapidly scanned to enable rapid acquisition of an OCT signal. In some embodiments, the laser source comprises a vertical cavity surface-emitting laser (VCSEL). In some embodiments, the VCSEL is tuned by varying the current supplied to the VCSEL. In some embodiments, the VCSEL is continuously scanned across a wavelength range by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a wavelength range by periodically varying the current. For example, the VCSEL may be supplied with a sinusoidally varying current to produce a sinusoidally varying wavelength.

[0135] In some embodiments, the front-end optical system comprises optical elements such as lenses. In some cases, the front-end optical system comprises any reflective, refractional, or diffracting elements. In other cases, the front-end optical system comprises two or more reflective, refractional, or diffracting elements. In some embodiments, the front-end optical system comprises electro-optical, magneto-optical, acoustic-optical, or mechanical-optical devices. The front-end optical system may comprise any optical elements known to those skilled in the art.

[0136] Figure 6B shows the wavelength ranges in which a VCSEL operates in a swept-source optical coherence tomography (SS-OCT) device lacking a reference mirror, according to several embodiments. In some cases, the VCSEL has a maximum recommended current for continuous use. In some embodiments, the maximum continuous current rating limits the range of wavelengths that the VCSEL can sweep. In some cases, the VCSEL is limited to a continuous operating current of 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, 9 mA, or 10 mA or less. In some cases, the wavelengths emitted by the VCSEL vary linearly with the operating current, with a proportionality constant of 0.3 nm / mA. In some embodiments, this limits the range of wavelengths that the VCSEL can sweep to 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, or 3.0 nm. In some cases, this limits the achievable axial resolution of a VCSEL-based SS-OCT device.

[0137] Therefore, in some cases, the limited operating range of a VCSEL limits the achievable axial resolution. For example, for a VCSEL with a central operating wavelength of 850 nm, the achievable axial resolution is as good as 1,062 μm, 531 μm, 354 μm, 266 μm, 213 μm, 177 μm, 152 μm, 133 μm, 118 μm, or 106 μm for operating ranges of 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, and 3.0 nm, respectively. In some embodiments, the VCSEL emits light intensities of 0.01mW, 0.025mW, 0.05mW, 0.1mW, 0.25mW, 0.5mW, 1mW, 2.5mW, 5mW, 10mW, 25mW, 50mW, 100mW, 250mW, 500mW, 1W, 2.5W, 5W, 10W, 25W, 50W, or 100W or less.

[0138] The light source does not necessarily have to be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous radiation (ASE). In other cases, the light source is a superluminescent diode (SLD). In addition, in some embodiments, the light source comprises multiple light sources.

[0139] Regardless of whether the SS-OCT device utilizes a reference mirror, the limited frequency range of the VCSEL allows the SS-OCT device to achieve an achievable axial resolution of less than approximately 100 μm.

[0140] Figure 7A shows a schematic diagram of the optical system of a sweep-source optical coherence tomography (SS-OCT) device utilizing a reference mirror, according to several embodiments. In some cases, the optical system 102 comprises a VCSEL or other light source 700, a beam splitter 710, a front-end optical system 720, a reference mirror 730, and a processing unit 740. In some embodiments, the processing unit further comprises a photodetector 742 and a signal processing module 744. Light from the light source strikes the beam splitter. Part of the light is directed along the reference arm to the reference mirror, and part of the light is directed to the front-end optical system and then to the sample 750. The light is back-reflected by the device at each boundary of each layer. The light reflected from each boundary interferes with the light reflected from the reference mirror and the light reflected from any other boundaries. The interference signal is detected by the photodetector.

[0141] This process is repeated over a range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength, reaching a maximum when the light reflected from one boundary and the light reflected from the reference mirror are in phase, or when the light reflected from one boundary is in phase with the light reflected from another boundary. This state is achieved at one or more specific wavelengths of light for each boundary and is characterized by one or more maximum values ​​of the interference signal. At other wavelengths, the interference signal exhibits either partial constructive or destructive interference. The interference signals at all wavelengths are compiled to form an interferogram. The interferogram undergoes a signal analysis procedure. In some cases, the interferogram undergoes a frequency analysis procedure, such as a Fast Fourier Transform (FFT), to form a spectrum. The spectrum has peaks corresponding to wavelengths associated with the maximum interference values ​​for each boundary. In some cases, SS-OCT utilizes a light source with a relatively long coherence length (typically exceeding several millimeters). In some embodiments, the amplitude of the interference signal decreases as the distance between the two retinal layers increases. In some cases, the position of the peaks indicates the thickness of each layer of tissue. The reference mirror allows for a longer optical path length for the light traveling to the sample. In some cases, this has a frequency-shifting effect, where the maximum interference signal is acquired at a higher frequency. In some embodiments, this shift to a higher frequency allows for the detection of the OCT signal in a manner that is more robust to noise.

[0142] In some cases, the light source comprises a laser source. In some embodiments, the laser source generates laser light having a tunable wavelength. In some cases, the laser source is scanned across a wavelength range to acquire an OCT signal. In some cases, the laser source can be rapidly scanned to enable rapid acquisition of an OCT signal. In some embodiments, the laser source comprises a vertical cavity surface-emitting laser (VCSEL). In some cases, the VCSEL is tuned by varying the current supplied to the VCSEL. In some cases, the VCSEL is continuously scanned across a wavelength range by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a wavelength range by periodically varying the current. For example, the VCSEL may be supplied with a sinusoidally varying current to produce a sinusoidally varying wavelength.

[0143] In some embodiments, the front-end optical system comprises optical elements such as lenses. In some cases, the front-end optical system comprises any reflective, refractional, or diffracting elements. In other cases, the front-end optical system comprises two or more reflective, refractional, or diffracting elements. In some embodiments, the front-end optical system comprises electro-optical, magneto-optical, acoustic-optical, or mechanical-optical devices. The front-end optical system may comprise any optical elements known to those skilled in the art.

[0144] In some cases, the front-end optical system includes scanning optical elements such as those described herein.

[0145] Figure 7B shows the wavelength ranges in which a VCSEL operates in a swept-source optical coherence tomography (SS-OCT) device lacking a reference mirror, according to several embodiments. The light source emits light with a central wavelength λ, which varies over a wavelength range Δλ.

[0146] Figure 7C illustrates how a reference mirror can shift the OCT peak to a higher optical frequency compared to the frequency of the OCT peak in the absence of the reference mirror. In the absence of a reference mirror, the OCT peak of a given sample is acquired at a relatively low frequency, denoted by t(encoded). This frequency corresponds to the optical path difference in the sample. The presence of a reference mirror has the effect that each boundary of the sample interferes with the reference mirror. For a sample with two boundaries, this effect produces two relatively high-frequency components in the OCT signal, represented as d(encoded) and d+t(encoded) in Figure 7C. The difference between these two frequencies corresponds to the distance between the boundaries of the sample. With respect to the retina or retinal layer, the difference therefore corresponds to RT or RLT, respectively.

[0147] In some cases, a VCSEL has a maximum recommended current for continuous use. In some embodiments, the maximum continuous current rating limits the range of wavelengths that the VCSEL can sweep. In some cases, the VCSEL is limited to continuous operating currents of 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, 9 mA, or 10 mA or less. In some cases, the wavelengths emitted by the VCSEL vary linearly with the operating current, with a proportionality constant of 0.3 nm / mA. In some embodiments, this current limit limits the range of wavelengths that the VCSEL can sweep. In some cases, the VCSEL is swept over a range defined by any two of the following numbers: 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, or 3.0 nm. In some cases, this sweep range limit limits the achievable axial resolution of a VCSEL-based SS-OCT device. In some embodiments, the sweep range is increased by driving a current exceeding the maximum current rating, as described herein.

[0148] Therefore, in some cases, the limited operating range of the VCSEL limits the achievable axial resolution. In some embodiments, for a VCSEL with a central operating wavelength of 850 nm, the achievable axial resolution is as good as 1,062 μm, 531 μm, 354 μm, 266 μm, 213 μm, 177 μm, 152 μm, 133 μm, 118 μm, or 106 μm for operating ranges of 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, and 3.0 nm, respectively. In some cases, VCSELs emit light intensities of 0.01mW, 0.025mW, 0.05mW, 0.1mW, 0.25mW, 0.5mW, 1mW, 2.5mW, 5mW, 10mW, 25mW, 50mW, 100mW, 250mW, 500mW, 1W, 2.5W, 5W, 10W, 25W, 50W, or 100W or less.

[0149] The light source does not necessarily have to be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous radiation (ASE). In other cases, the light source is a superluminescent diode (SLD). In addition, in some embodiments, the light source comprises multiple light sources.

[0150] In some cases, the limited achievable axial resolution can be improved by utilizing two or more VCSELs or other light sources within the SS-OCT system. In some embodiments, each of the two or more VCSELs or other light sources has an emission spectrum distinctly different from the emission spectra of the other VCSELs or other light sources. In some cases, the emission spectra of the two or more VCSELs partially overlap. In other cases, the emission spectra of the two or more VCSELs do not overlap. In this way, in some embodiments, the two or more VCSELs or other light sources merge to produce a wider range of emission wavelengths for SS-OCT measurements. In some cases, this enhances the achievable axial resolution of the SS-OCT measurement.

[0151] Figure 8A shows the optical systems of a sweep-source optical coherence tomography (SS-OCT) device utilizing two VCSELs and lacking a reference mirror, at a first specific time point, according to several embodiments. In some cases, the optical system 102 comprises a first VCSEL or other light source 800, a second VCSEL or other light source 805, a first beam splitter 810, a second beam splitter 815, a front-end optical system 820 as described herein, and a processing unit 840. In some embodiments, the processing unit further comprises a photodetector 842 and a signal processing module 844. Light from the first light source collides with the beam splitter. The light is directed to the front-end optical system and then to the sample 850. In some cases, at a first specific time point, the first VCSEL or other light source is on (transmitting laser light to the sample), while the second VCSEL or other light source is off (not transmitting laser light to the sample). Light is reflected back by the device at each boundary of each layer. The light reflected from the boundary of the first layer interferes with the light reflected from the back boundary of the second layer. The interference signal is detected by a photodetector.

[0152] Figure 8B shows schematic diagrams of sweep-source optical coherence tomography (SS-OCT) devices utilizing two VCSELs and lacking a reference mirror, according to several embodiments, at a second specific time point. In one example, at the second specific time point, the first VCSEL or other light source is off (not transmitting laser light to the sample), while the second VCSEL or other light source is on (transmitting laser light to the sample). Light is back-reflected by the device at each boundary of each layer. Light reflected from the boundary of the first layer interferes with light reflected from the boundary of the second layer. The interference signal is detected by a photodetector.

[0153] This process is repeated across the entire range of wavelengths emitted by the first and second light sources. The amplitude of the interference signal varies with wavelength, reaching a maximum when the light reflected from one boundary and the light reflected from the reference mirror are in phase, or when the light reflected from one boundary is in phase with the light reflected from another boundary. This state is achieved at one or more specific wavelengths of light for each boundary and is characterized by one or more maximum values ​​of the interference signal. At other wavelengths, the interference signal exhibits either partial constructive or destructive interference. The interference signals at all wavelengths are compiled to form an interferogram. The interferogram undergoes a signal analysis procedure. In some cases, the interferogram undergoes a frequency analysis procedure, such as a Fast Fourier Transform (FFT), to form a spectrum. The spectrum has peaks corresponding to the wavelengths associated with the maximum interference values ​​for each boundary. In some cases, SS-OCT utilizes light sources with short coherence lengths (typically less than a few millimeters). In such cases, the amplitude of the interference signal decreases rapidly as the wavelength moves away from the wavelength associated with the maximum interference value. In some embodiments, this results in a narrow peak in the frequency spectrum. In one instance, the distance between the peaks indicates the thickness of each layer of tissue.

[0154] In some cases, the light source comprises a laser source. In some embodiments, the laser source generates laser light having a tunable wavelength. In some cases, the laser source is scanned across a wavelength range to acquire an OCT signal. In some cases, the laser source can be rapidly scanned to enable rapid acquisition of an OCT signal. In some embodiments, the laser source comprises a vertical cavity surface-emitting laser (VCSEL). In some cases, the VCSEL is tuned by varying the current supplied to the VCSEL. In some cases, the VCSEL is continuously scanned across a wavelength range by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a wavelength range by periodically varying the current. For example, the VCSEL may be supplied with a sinusoidally varying current to produce a sinusoidally varying wavelength.

[0155] In some embodiments, the front-end optical system comprises optical elements such as lenses. In some cases, the front-end optical system comprises any reflective, refractional, or diffracting elements. In other cases, the front-end optical system comprises two or more reflective, refractional, or diffracting elements. In some embodiments, the front-end optical system comprises electro-optical, magneto-optical, acoustic-optical, or mechanical-optical devices. In some cases, the front-end optical system comprises any optical elements known to those skilled in the art.

[0156] In some cases, the front-end optical system includes a scanning optical element to allow the light source to be moved to different locations on the retina. In some cases, this allows multiple measurements to be taken to determine RT or RLT at different locations on the retina. In some embodiments, the scanning optical element includes a galvanometer. In some embodiments, the scanning optical element includes an acousto-optic modulator. In some cases, the scanning optical element includes an electro-optic modulator. In some embodiments, the scanning optical element includes an xy stage. The scanning optical element may include any scanning optical element known to those skilled in the art.

[0157] Figure 8C shows the wavelength ranges in which VCSELs operate in a swept-source optical coherence tomography (SS-OCT) device that utilizes two VCSELs and lacks a reference mirror, according to several embodiments.

[0158] Wavelength sweep can be coordinated in various ways between two or more VCSELs or other light sources. In one embodiment, a first VCSEL or other light source is swept across its entire wavelength range while a second VCSEL or other light source is off. The second VCSEL or other light source is then swept across its entire wavelength range while the first VCSEL or other light source is off. Wavelength sweep occurs alternately between the two VCSELs or other light sources until the entire SS-OCT signal is acquired. In some cases, the second VCSEL is configured to emit light having a wavelength within about 0.1 nm of the first VCSEL when the first VCSEL is turned off. In some embodiments, the VCSELs are swept at a rate between about 50 Hz and about 10 kHz. In some cases, the VCSELs are swept at a rate between about 1 kHz and about 5 kHz.

[0159] In another embodiment, two or more VCSELs undergo their wavelength sweep simultaneously and at the same rate. In such a setup, it may be helpful to eliminate the temporal correlation between the OCT signals from the first VCSEL or other light source and the OCT signals from the second VCSEL or other light source. This can be accomplished, for example, by modifying the optical setup in Figure 8A and including a spectrometer instead of a photodetector, as will be readily understood by those skilled in the art. In some cases, the sweep frequencies of the two VCSELs are substantially identical. In some embodiments, the sweep rates of the two VCSELs are within 5% of each other. In some cases, the sweep rates of the two VCSELs are within 1% of each other. In some cases, the VCSELs are swept at a rate between about 50 Hz and about 10 kHz. In some embodiments, the VCSELs are swept at a rate between about 1 kHz and about 5 kHz.

[0160] In another embodiment, two or more VCSELs undergo wavelength sweeps simultaneously but at different rates. For example, a first VCSEL or other light source may be swept over a range of its emission wavelengths at a first rate so as to complete its wavelength sweep in a first time quantity. A second VCSEL or other light source is swept over a range of its emission wavelengths at a second rate different from the first rate so as to complete its wavelength sweep in a second time quantity different from the first rate. In this way, the SS-OCT signal from the first VCSEL or other light source is temporally encoded in a manner different from the temporal encoding of the SS-OCT signal from the second VCSEL or other light source. The SS-OCT signal from the first VCSEL or other light source is then distinguished from the SS-OCT signal from the second VCSEL or other light source through signal processing means. In some cases, the VCSELs are swept at a rate between about 50 Hz and about 10 kHz. In some embodiments, the VCSELs are swept at a rate between about 1 kHz and about 5 kHz.

[0161] In some embodiments, the system comprises two, three, four, five, six, seven, eight, nine, ten, or more VCSELs or other light sources. In some cases, each VCSEL has a maximum recommended current for continuous use. In some cases, the maximum continuous operating current rating limits the range of wavelengths that each VCSEL can sweep. For example, each VCSEL may be limited to a continuous operating current of 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, 9 mA, or 10 mA or less. In some cases, the wavelength emitted by each VCSEL varies linearly with the operating current, with a proportionality constant of 0.3 nm / mA. In some embodiments, this limits the range of wavelengths that each VCSEL can sweep to 0.3 nm, 0.6 nm, 0.9 nm, 1.2 nm, 1.5 nm, 1.8 nm, 2.1 nm, 2.4 nm, 2.7 nm, or 3.0 nm. In some cases, combinations of 2, 3, 4, 5, 6, 7, 8, 9, 10, or more VCSELs or other light sources can generate the entire wavelength range up to 30 nm or beyond. In other cases, the use of multiple VCSELs allows for a swept wavelength range, for example, within the range of 5 nm to 10 nm.

[0162] Therefore, in some cases, a wider overall operating range of 2, 3, 4, 5, 6, 7, 8, 9, 10, or more VCSELs enhances the attainable axial resolution. In some embodiments, with respect to a set of two VCSELs, each with a central operating wavelength of approximately 850 nm, the attainable axial resolution is 53 μm, given that each VCSEL has an operating range of 3.0 nm. With three VCSELs, the attainable axial resolution is 35 μm, given that each VCSEL has an operating range of 3.0 nm. With four VCSELs, the attainable axial resolution is 27 μm, given that each VCSEL has an operating range of 3.0 nm. In some cases, as the number of VCSELs increases further, the attainable axial resolution is further enhanced. In some embodiments, each VCSEL emits light intensities of 0.01mW, 0.025mW, 0.05mW, 0.1mW, 0.25mW, 0.5mW, 1mW, 2.5mW, 5mW, 10mW, 25mW, 50mW, 100mW, 250mW, 500mW, 1W, 2.5W, 5W, 10W, 25W, 50W, or 100W or less.

[0163] In some cases, limited attainable axial resolution can also be improved by providing a maximum current above the rated current to the VCSEL or other light source. VCSELs are typically rated with respect to maximum current under the assumption that they will be subjected to a high duty cycle. However, VCSELs may be able to withstand currents above their rated current for short periods. In handheld SS-OCT devices, the VCSEL may be driven only at operating currents outside its rated range for the period required to acquire OCT measurements. In some cases, the VCSEL is driven at operating currents outside its rated range for less than one minute at a time. In some cases, the VCSEL is driven at operating currents outside its rated range infrequently. For example, in some cases, the VCSEL is driven at operating currents outside its rated range once every few hours. In some cases, the VCSEL is driven at operating currents outside its rated range once every few days. In some embodiments, the VCSEL is turned off for periods when it is not driven at operating currents outside its rated range. In other embodiments, the VCSEL is driven at lower operating currents within its rated range for such periods. Therefore, in some cases, a VCSEL can withstand being driven at a higher current than its rated value under the operating conditions expected for a handheld SS-OCT device.

[0164] Figure 9 illustrates the operation of a VCSEL above its maximum current rating. In some cases, the current supplied to the VCSEL varies over time according to a certain waveform 900. The waveform can be triangular, sinusoidal, or any other waveform known to those skilled in the art. In some embodiments, the VCSEL has a recommended continuous current range defined by an upper current threshold 910 and / or a lower current threshold 920. At different points in the waveform, the VCSEL is supplied with a current that exceeds the upper current threshold or falls below the lower current threshold. In some cases, the maximum current exceeds the upper current threshold by more than 10%, more than 20%, more than 50%, more than 100%, more than 200%, more than 300%, more than 400%, or more than 500%. In some embodiments, the VCSEL is swept at a rate between approximately 50 Hz and approximately 10 kHz. In some cases, the VCSEL is swept at a rate between approximately 1 kHz and approximately 5 kHz.

[0165] In some cases, exceeding the maximum current allows the VCSEL to be driven beyond a specified maximum wavelength range directly related to its maximum recommended current for continuous use. In some cases, the VCSEL is driven beyond its specified wavelength range by at least about 1 nm. In some cases, the VCSEL is driven beyond its specified wavelength range by an amount in the range of 1 nm to 5 nm. In some embodiments, driving the VCSEL beyond its specified wavelength range allows for a wavelength range in the range of 5 nm to 10 nm. In some cases, the VCSEL is driven beyond its maximum wavelength range for each of multiple measurements. To avoid overheating of the VCSEL, there may be a delay implemented between continuous measurements. In some cases, the delay ranges from about 1 millisecond to about 100 milliseconds. In some cases, the delay ranges from about 5 milliseconds to about 20 milliseconds.

[0166] In some cases, the limited achievable axial resolution obtained by a single VCSEL with a limited range of motion does not raise technical issues, including measuring the thickness of a specific structure but not attempting to measure substructures within it. For example, it may be considered to acquire RT or RLT measurements without considering imaging substructures within the retina. Furthermore, it may be considered to be primarily interested in the measured changes in RT or RLT. In some cases, it may be possible to acquire RT or RLT measurements with higher precision than might be expected from the achievable axial resolution.

[0167] Figure 10A shows a graphical representation of the axial resolution. The SS-OCT device used to measure RT or RLT generates a first interference signal 1000 associated with light reflected from a first boundary of tissue layers and a second interference signal 1002 associated with light reflected from a second boundary of tissue layers. The interference signals 1000 and 1002 are represented in the frequency domain. The first signal has a maximum value at optical path difference Δz1. The second signal has a maximum value at optical path difference Δz2. Each signal peak has an associated width. The first and second interference signals can be said to be resolved when the two signals do not completely overlap and provide distinguishable peaks. Maximum overlap occurs when the two signals would no longer be distinguishable if they overlapped further. The distance between the first and second peaks at the point of maximum overlap is the axial resolution. The width is inversely correlated with the range of wavelengths swept by the SS-OCT light source. Therefore, for SS-OCT devices that utilize a relatively narrow range of wavelengths, the axial resolution may fall below ideal.

[0168] With regard to RT measurement, the axial resolution should be sufficient to distinguish between a first interference signal associated with the first interface of the tissue layers and a second interference signal associated with the second interface of the tissue layers. Since the retina typically has an RT greater than 150 μm, SS-OCT devices capable of measuring RT can achieve an axial resolution value of less than approximately 150 μm.

[0169] Figure 10B shows a graphical representation of repeatability and reproducibility. Repeatability refers to the variability in measurements obtained by a single instrument with the same item over a short period of time (e.g., within 1 minute, 1 hour, or 1 day) under similar conditions. Reproducibility refers to the variability in measurements obtained by a single instrument with the same sample over a longer period of time (e.g., after 1 day, 1 week, 1 month, 3 months, or 6 months) under similar conditions. Repeatability can be quantitatively expressed as the full width at half maximum (FWHM) of the distribution of values ​​obtained during repeated measurements by a single instrument over a relatively short period of time under similar conditions. Reproducibility can be quantitatively expressed as the difference between the median of the distribution of first values ​​obtained by a single instrument under a first set of conditions over a first short period of time and the median of the distribution of second values ​​obtained by a single instrument under a second set of conditions over a second short period of time. With regard to RT measurements, a combination of repeatability and reproducibility can be used to set tolerances to determine whether changes in RT or RLT measurements are due to noise or to actual changes in retinal thickness.

[0170] Figure 10C shows a graphical representation of repeatability and reproducibility associated with RT or RLT measurements of a retina that does not exhibit a change in RT or RLT. At the first time point, the RT measurements follow a distribution 1020 determined by repeatability. At subsequent time points, the RT or RLT measurements are obtained from a distribution 1022 as determined by repeatability and reproducibility. With respect to a retina that does not exhibit a change in RT or RLT, the two distributions 1020 and 1022 are in close proximity to each other such that Δx is within the composite repeatability and reproducibility. However, if Δx exceeds the composite repeatability and reproducibility, the increase in retinal thickness is identified and reported to the patient and healthcare provider, for example, using an alert, as more fully explained in Figure 10D. In many embodiments, the miniature OCT device has a composite repeatability and reproducibility of less than approximately 35 μm. In some embodiments, the SS-OCT device has a composite repeatability and reproducibility of less than 25 μm with a 95% confidence level.

[0171] Figure 10D shows a graphical representation of repeatability and reproducibility associated with RT or RLT measurements of a retina exhibiting a change in RT or RLT. At a first time point, the RT or RLT is obtained within a first distribution 1030 determined by repeatability. At subsequent time points, the RT or RLT is obtained within a second distribution 1032, similarly determined by repeatability. With respect to a retina exhibiting a change in RT or RLT, the two distributions 1030 and 1032 are no longer in close proximity to each other. When the distance between the two distributions 1030 and 1032 exceeds the combination of repeatability and reproducibility, it can be determined that the RT or RLT has changed. The distance between the two distributions can be determined by determining the difference between the individual means of the two distributions. The system can determine that a change in RT or RLT has occurred when the measurement is separated by a value exceeding the combination of repeatability and reproducibility. For example, this would be approximately 35 μm with respect to a reproducibility of 25 μm and repeatability of 25 μm. Alternatively, if there is systematic error or long-term drift, the combined error may be greater than 35 μm with respect to 25 μm reproducibility and 25 μm repeatability. Thus, the peaks in the distribution for the first RT measurement at 150 μm and the second RT measurement at 200 μm will be separated by 50 μm. Although the first and second measurements have been shown to have non-overlapping distributions, the methods and apparatus described herein are capable of determining RT or RLT with respect to partially overlapping distributions of measurements.

[0172] In some cases, RT or RLT measurements obtained by a handheld OCT device are compared to a reference measurement. In some embodiments, the reference measurement is obtained from measurements taken by a clinical OCT device. In some cases, the reference measurement is obtained during a patient visit with their healthcare provider. In some cases, the reference measurement is stored on a handheld OCT device, a patient device (such as a smartphone or other portable electronic device), or a cloud-based storage and communication system. In some embodiments, the reference measurement is used to adjust the measurements from a miniature OCT device, for example, to account for any systematic errors in the measurements.

[0173] Therefore, when it is desired to obtain a measured change in RT or RLT, it may be possible to obtain a detection limit that is substantially better than the axial resolution obtainable for OCT imaging set by equation 1. In some cases, the handheld OCT devices described herein achieve a repeatability of about 25 μm. In some embodiments, the handheld OCT devices described herein are capable of detecting RT or RLT changes of about 25 μm. In some cases, the handheld OCT devices described herein are capable of detecting RT or RLT changes in the range of 10 μm to 40 μm with a confidence of better than 95%. In some cases, the handheld OCT devices described herein are capable of detecting RT or RLT changes in the range of 20 μm to 30 μm with a confidence of better than 95%.

[0174] In many embodiments, the miniature OCT system is calibrated to a specific patient using a high-resolution clinical OCT reference system having a resolution value lower than that of the miniature OCT system. For example, the patient may visit an ophthalmologist, and the retinal thickness may be measured in the clinic using a high-resolution ultrasound system. The miniature OCT system can then be calibrated to a specific patient based on the retinal thickness measured using the clinical reference system. This calibration of the miniature OCT system based on the high-resolution OCT system can be performed within one day of the high-resolution ultrasound system measurement, preferably within about two hours of the clinical high-resolution ultrasound measurement, and in many cases, while the patient is in the clinic.

[0175] In some embodiments, the devices described herein are capable of continuous operation after a drop. In some cases, the devices described herein are capable of withstanding drops with a 95% survival rate during a drop test. In some cases, the drop test consists of dropping the device from 1 foot (0.305 m), 2 feet (0.610 m), 3 feet (0.914 m), and 4 feet (1.219 m). In some embodiments, the devices described herein are capable of continuous operation after a drop test with repeatability changes of 30 μm or less. In some embodiments, the device is capable of continuous operation after a drop test with repeatability changes of 20 μm or less. In some embodiments, the device is capable of continuous operation after a drop test with repeatability changes of 15 μm or less. In some embodiments, the device is capable of continuous operation after a drop test with repeatability changes of 10 μm or less. In some embodiments, the device is capable of continuous operation after a drop test with repeatability changes of 5 μm or less.

[0176] Figure 11 is a flowchart of a method for repeatedly measuring the thickness of a patient's retina (RT) over time and noting changes that may indicate an undesirable outcome. Method 1100 consists of the steps of inputting patient data, grasping a handheld OCT device, directing a beam of light into the patient's eye, receiving reflected light from the patient's retina, determining the thickness of the retina, repeating the measurement for multiple measurements separated by at least several hours, determining changes in RT, and generating an alert.

[0177] In step 1102, patient data is entered into a handheld OCT device as described herein. If any, the patient data may include the patient's name, age, sex, height, weight, current ophthalmic problems, and current medical problems.

[0178] In step 1104, the patient grasps the handheld OCT device described herein. The patient looks into the handheld OCT device.

[0179] In step 1106, a handheld OCT device directs a beam of light into the patient's eye. The light is reflected from the boundaries of various layers in the patient's retina.

[0180] In step 1108, the handheld OCT receives light reflected from various layers of the patient's retina. The reflected light forms an interference signal that is detected by the photodetector. In some cases, the interference signal is generated by the interference of reflected light from light that has crossed the reference arm of the handheld OCT device. In other cases, the interference signal is generated by the interference between light reflected from two or more boundaries of various layers of the retina. The handheld OCT device varies the wavelength of light directed towards the eye and records the interference signal for each wavelength.

[0181] In step 1110, the patient's RT or RLT is determined. In some cases, RT or RLT is determined by a mathematical analysis of the OCT signal. For example, RT or RLT may be determined from the Fast Fourier Transform of the OCT signal. RT or RLT may be determined from any other frequency analysis of the OCT signal. RT or RLT may be determined by comparing the frequency components of the OCT signal with a calibration curve that maps RT or RLT to frequencies. In some embodiments, the calibration curve is general to all patients. In some cases, the calibration curve is specific to the individual patient.

[0182] In step 1112, the measurement is repeated for multiple measurements separated by at least several hours. For each measurement, steps 1102, 1104, 1106, 1108, and 1110 are repeated.

[0183] In step 1114, the change in RT or RLT is determined. If any, the value of RT or RLT determined in the most recent measurement is compared to any previous measurement. In some embodiments, the change in the value of RT or RLT is recorded and tracked over the course of many measurements.

[0184] In step 1116, an alert is triggered if RT or RLT changes significantly, or if RT or RLT is outside the normal or healthy range. In some cases, the alert includes a notification displayed on a mobile patient device as described herein. In some embodiments, the alert may include a notification sent to the patient's physician or other healthcare provider, as described herein.

[0185] In some cases, a first RT or RLT is measured using a handheld OCT device within 24 hours of an ophthalmologist's visit. In some embodiments, a second RT or RLT is measured within a range of 1 to 20 days after the first measurement. In some cases, RT or RLT is measured daily over multiple days within a range of approximately 5 to 20 days. In some cases, RT or RLT is measured more frequently than once a day. In some embodiments, RT or RLT is measured over a period longer than 20 days. Changes in RT or RLT are determined in response to a baseline thickness and multiple subsequent thicknesses. In some cases, changes in RT or RLT are measured with confidence intervals of at least 90%, at least 95%, or at least 99%.

[0186] Figure 12 shows a flowchart of a method for determining RT from measurements using a handheld OCT device. Method 1200 includes the steps of directing a light beam to the retina, generating an interference signal, capturing the interference pattern using a detector, varying the wavelength of the light directed to the retina, processing the interference signal and determining the peak, fitting the resulting peak to a sine wave, and determining RT or RLT.

[0187] In step 1202, a handheld OCT device directs a beam of light into the patient's eye. The light is reflected from the boundaries of various layers in the patient's retina.

[0188] In step 1204, the handheld OCT receives light reflected from the boundaries of various layers of the patient's retina. The reflected light forms an interference signal. In some cases, the interference signal is generated by the interference of reflected light with light that has crossed the reference arm of the handheld OCT device. In other cases, the interference signal is generated by the interference between light reflected from two or more boundaries of various layers of the retina.

[0189] In step 1206, the interference signal is detected by the photodetector.

[0190] In step 1208, the handheld OCT device varies the wavelength of light directed towards the retina. Steps 1202, 1204, and 1206 are repeated for each wavelength. Interference signals are recorded for each wavelength.

[0191] In step 1210, the interference signal is processed to determine the peak. In some cases, the peak corresponds to the maximum interference between light reflected from various layers of the retina and light crossing the reference arm of the handheld OCT device. In other cases, the peak corresponds to the maximum interference between light reflected from the boundaries of various layers of the retina and light crossing the reference arm of the handheld OCT device. In other cases, the peak corresponds to the maximum interference between light reflected from the boundaries of two or more layers of the retina.

[0192] In step 1212, the resulting peak is fitted to a sine wave. In some cases, the fitting is done via a nonlinear least-squares fitting. In some embodiments, the fitting is done via any other fitting method known to those skilled in the art.

[0193] In step 1214, RT or RLT is determined. In some cases, RT or RLT is determined by extracting the frequency of a fitted sine wave. In some embodiments, RT or RLT is determined by comparing the frequency components of the OCT signal with a calibration curve that maps RT to frequency. In some cases, the calibration curve is general to all patients. In other cases, the calibration curve is specific to individual patients.

[0194] One of ordinary skill in the art will recognize many variations, modifications, and adaptations based on the disclosure provided herein. For example, the order of the steps of methods 1100 and / or 1200 can be changed, some of the steps can be removed, some of the steps can be repeated, and additional steps can be added as appropriate. The methods 1100 and 1200 can be combined. Some of the steps can include sub-steps. Some of the steps can be automated and some of the steps can be manual. A processor as described herein can include one or more instructions for performing at least a portion of one or more of the steps of methods 1100 and / or 1200. (Digital processing device)

[0195] In some embodiments, the platforms, systems, media, and methods described herein include the use of a digital processing device or the like. In further embodiments, the digital processing device includes one or more hardware central processing units (CPUs) or general purpose processing units (GPGPUs) that implement the functions of the device. In still further embodiments, the digital processing device further includes an operating system configured to execute executable instructions. In some embodiments, the digital processing device is optionally connected to a computer network. In further embodiments, the digital processing device is optionally connected to the Internet to access the World Wide Web. In still further embodiments, the digital processing device is optionally connected to a cloud computing infrastructure. In other embodiments, the digital processing device is optionally connected to an intranet. In other embodiments, the digital processing device is optionally connected to a data storage device.

[0196] According to the description in this specification, suitable digital processing devices include, as non-limiting examples, server computers, desktop computers, laptop computers, notebook computers, sub-notebook computers, netbook computers, netpad computers, set-top computers, media streaming devices, handheld computers, Internet appliances, mobile smartphones, tablet computers, personal digital assistants, video game consoles, and vehicles. Those skilled in the art will recognize that many smartphones are suitable for use in the systems described in this specification. Those skilled in the art will also recognize that select televisions, video players, and digital music players with optional computer network connectivity are suitable for use in the systems described in this specification. Suitable tablet computers include those with a convertible, slate, and booklet form factor known to those skilled in the art.

[0197] In some embodiments, the digital processing device includes an operating system configured to execute executable instructions. The operating system is software, including programs and data that, for example, manage the device's hardware and provide services for running applications. A person skilled in the art will recognize that, in non-limiting embodiments, preferred server operating systems include FreeBSD, OpenBSD, NetBSD, Linux, Apple Mac OS X Server, Oracle Solaris, Windows Server, and Novell NetWare. A person skilled in the art will recognize that, in non-limiting embodiments, preferred personal computer operating systems include UNIX-like operating systems such as Microsoft Windows, Apple Mac OS X, UNIX, and GNU / Linux. In some embodiments, the operating system is provided by cloud computing. Those skilled in the art will also recognize that suitable mobile smartphone operating systems include, in non-limiting embodiments, Nokia® Symbian® OS, Apple® iOS®, Research In Motion® BlackBerry OS®, Google® Android®, Microsoft® Windows® Phone® OS, Microsoft® Windows® Mobile® OS, Linux®, and Palm® WebOS®.Those skilled in the art will also recognize that suitable media streaming device operating systems include, in non-limiting embodiments, Apple TV®, Roku®, Boxee®, Google TV®, Google Chromecast®, Amazon Fire®, and Samsung® HomeSync®. Those skilled in the art will also recognize that suitable video game console operating systems include, in non-limiting embodiments, Sony® PS3®, Sony® PS4®, Microsoft® Xbox 360®, Microsoft Xbox One, Nintendo® Wii®, Nintendo® Wii U®, and Ouya®.

[0198] In some embodiments, the device includes a storage and / or memory device. A storage and / or memory device is one or more physical devices used to store data or programs temporarily or permanently. In some embodiments, the device is volatile memory and requires power to maintain the stored information. In some embodiments, the device is non-volatile memory and retains the stored information when the digital processing device is not powered. In further embodiments, the non-volatile memory comprises flash memory. In some embodiments, the non-volatile memory comprises dynamic random access memory (DRAM). In some embodiments, the non-volatile memory comprises ferroelectric random access memory (FRAM®). In some embodiments, the non-volatile memory comprises phase-change random access memory (PRAM). In other embodiments, the device is a storage device that, in non-limiting embodiments, includes CD-ROMs, DVDs, flash memory devices, magnetic disk drives, magnetic tape drives, optical disk drives, and cloud computing-based storage devices. In further embodiments, the storage and / or memory device is a combination of devices such as those disclosed herein.

[0199] In some embodiments, the digital processing device includes a display for transmitting visual information to the user. In some embodiments, the display is a cathode ray tube (CRT). In some embodiments, the display is a liquid crystal display (LCD). In further embodiments, the display is a thin-film transistor liquid crystal display (TFT-LCD). In some embodiments, the display is an organic light-emitting diode (OLED) display. In various further embodiments, the OLED display is a passive-matrix OLED (PMOLED) or an active-matrix OLED (AMOLED) display. In some embodiments, the display is a plasma display. In other embodiments, the display is a video projector. In yet further embodiments, the display is a combination of devices such as those disclosed herein.

[0200] In some embodiments, the digital processing device includes an input device for receiving information from a user. In some embodiments, the input device is a keyboard. In some embodiments, the input device is a pointing device, including, in non-limiting embodiments, a mouse, trackball, trackpad, joystick, game controller, or stylus. In some embodiments, the input device is a touchscreen or multitouchscreen. In other embodiments, the input device is a microphone for capturing voice or other sound input. In other embodiments, the input device is a video camera or other sensor for capturing motion or visual input. In further embodiments, the input device is Kinect, Leap Motion, or equivalent. In even further embodiments, the input device is a combination of devices such as those disclosed herein.

[0201] Referring to Figure 13, in certain embodiments, the exemplary digital processing device 1301 is programmed or otherwise configured to determine RT or RLT. The device 1301 can coordinate various aspects of the RT or RLT determination of this disclosure, such as performing processing steps. In these embodiments, the digital processing device 1301 includes a central processing unit (CPU, also referred to herein as “processor” and “computer processor”) 1305, which may be a single-core or multi-core processor, or multiple processors for parallel processing. The digital processing device 1301 also includes memory or memory locations 1310 (e.g., random-access memory, read-only memory, flash memory), electronic storage units 1315 (e.g., hard disks), communication interfaces 1320 for communicating with one or more other systems (e.g., network adapters), and peripheral devices 1325 such as caches, other memory, data storage, and / or electronic display adapters. The memory 1310, storage unit 1315, interface 1320, and peripheral device 1325 communicate with the CPU 1305 through a communication bus (solid wire) such as a motherboard. The storage unit 1315 may be a data storage unit (or data repository) for storing data. The digital processing device 1301 may be operably coupled to a computer network ("network") 1330 with the help of the communication interface 1320. The network 1330 may be the internet, the internet and / or extranet, or an intranet and / or extranet communicating with the internet. The network 1330 may, in some cases, be a telecommunications and / or data network. The network 1330 may include one or more computer servers that may enable distributed computing such as cloud computing. The network 1330 may, in some cases, implement a peer-to-peer network that may, with the help of device 1301, allow devices coupled to device 1301 to behave as clients or servers.

[0202] Continuing to refer to Figure 13, the CPU 1305 can execute a set of machine-readable instructions, which may be embodied in a program or software. The instructions may be stored in a memory location, such as memory 1310. The instructions can be directed to the CPU 1305, which can then be programmed or otherwise configured to implement the methods of this disclosure. Embodiments of operations performed by the CPU 1305 may include fetching, decoding, executing, and writing back. The CPU 1305 may be part of a circuit, such as an integrated circuit. One or more other components of device 1301 may be included in the circuit. In some cases, the circuit is an application-specific integrated circuit (ASIC) or a field-programmable gate array (FPGA).

[0203] Continuing to refer to Figure 13, the storage unit 1315 can store files such as drivers, libraries, and saved programs. The storage unit 1315 can also store user data, such as user preferences and user programs. The digital processing device 1301 may include one or more additional data storage units located externally, such as on a remote server communicating over an intranet or the internet.

[0204] Continuing to refer to Figure 13, the digital processing device 1301 can communicate with one or more remote computer systems through the network 1330. For example, device 1301 can communicate with a user's remote computer system. Embodiments of a remote computer system include personal computers (e.g., portable PCs), slate or tablet PCs (e.g., Apple® iPad®, Samsung® Galaxy Tab), telephones, smartphones (e.g., Apple® iPhone®, Android-enabled devices, Blackberry®), or personal digital assistants.

[0205] The methods described herein can be implemented, for example, via machine-executable code stored on an electronic storage location of a digital processing device 1301, such as memory 1310 or electronic storage unit 1315. The machine-executable or machine-readable code can be provided in the form of software. In use, the code can be executed by the processor 1305. In some cases, the code can be read from the storage unit 1315 and stored on memory 1310 for easy access by the processor 105. In some situations, the electronic storage unit 1315 can be omitted, and the machine-executable instructions are stored on memory 1310.

[0206] (Non-transient computer-readable storage medium) In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more non-transient computer-readable storage media encoded with a program containing instructions executable by an operating system of a optionally networked digital processing device. In further embodiments, the computer-readable storage medium is a tangible component of the digital processing device. In yet another embodiment, the computer-readable storage medium is optionally removable from the digital processing device. In some embodiments, the computer-readable storage medium includes, in non-limiting embodiments, CD-ROMs, DVDs, flash memory devices, solid-state memory, magnetic disk drives, magnetic tape drives, optical disk drives, cloud computing systems and services, and equivalents. In some cases, the programs and instructions are encoded permanently, substantially permanently, semi-permanently, or non-transiently on the medium.

[0207] (Computer program) In some embodiments, the platforms, systems, media, and methods disclosed herein involve the use of at least one computer program or identical thereof. A computer program includes a set of instructions executable on the CPU of a digital processing device, which are written to perform a specified task. Computer-readable instructions may be implemented as program modules such as functions, objects, application programming interfaces (APIs), data structures, and equivalents, which perform a particular task or implement a particular abstract data type. In light of the disclosures provided herein, those skilled in the art will recognize that computer programs may be written in various versions of various languages.

[0208] The functionality of computer-readable instructions can be combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer program comprises multiple sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from multiple locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plugins, extensions, add-ins or add-ons, or a combination thereof.

[0209] (Web application) In some embodiments, the computer program includes a web application. Those skilled in the art will recognize, based on the disclosures provided herein, that the web application utilizes, in various embodiments, one or more software frameworks and one or more database systems. In some embodiments, the web application is built on a software framework such as Microsoft® .NET or Ruby on Rails (RoR). In some embodiments, the web application utilizes one or more database systems, including, in non-limiting embodiments, relational, non-relational, object-oriented, associative, and XML database systems. In further embodiments, preferred relational database systems, in non-limiting embodiments, include Microsoft® SQL Server and MySQL. TM, and Oracle®, including. Those skilled in the art will also recognize that web applications may, in various embodiments, be written in one or more versions of one or more languages. A web application may be written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or a combination thereof. In some embodiments, a web application may be written to some extent in a markup language such as Hypertext Markup Language (HTML), Extensible Hypertext Markup Language (XHTML), or Extensible Markup Language (XML). In some embodiments, a web application may be written to some extent in a presentation definition language such as Cascading Style Sheets (CSS). In some embodiments, a web application may be written to some extent in a client-side scripting language such as Asynchronous Java® Script and XML (AJAX), Flash® ActionScript, Java® Script, or Silverlight®. In some embodiments, the web application uses, to some extent, Active Server Pages (ASP), ColdFusion (registered trademark), Perl, Java (registered trademark), Java Server Pages (JSP), Hypertext Preprocessor (PHP), and Python. TMThe web application is written in a server-side coding language such as Ruby, Tcl, Smalltalk, WebDNA®, or Groovy. In some embodiments, the web application is written to some extent in a database query language such as a structured query language (SQL). In some embodiments, the web application integrates with enterprise server products such as IBM® Lotus Domino®. In some embodiments, the web application includes a media player element. In various further embodiments, the media player element utilizes one or more of many preferred multimedia technologies, including, in non-limiting embodiments, Adobe® Flash®, HTML 5, Apple® QuickTime®, Microsoft® Silverlight®, Java®, and Unity®.

[0210] (Mobile application) In some embodiments, the computer program includes a mobile application provided to a mobile digital processing device. In some embodiments, the mobile application is provided to the mobile digital processing device at the time it is manufactured. In other embodiments, the mobile application is provided to the mobile digital processing device via a computer network as described herein.

[0211] In light of the disclosures provided herein, mobile applications are created using hardware, languages, and development environments known in the art, and techniques known to those skilled in the art. Those skilled in the art will recognize that mobile applications are written in several languages. Preferred programming languages, in non-limiting embodiments, include C, C++, C#, Objective-C, Java®, Javascript, Pascal, Object Pascal, and Python. TMThis includes Ruby, VB.NET, WML, and XHTML / HTML with or without CSS, or a combination thereof.

[0212] Suitable mobile application development environments are available from several sources. Commercially available development environments, in non-exclusive examples, include AirplaySDK, alcheMo, Appcelerator®, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments, in non-exclusive examples, include Lazarus, MobiFlex, MoSync, and Phonegap, which are available free of charge. Mobile device manufacturers also offer, in non-exclusive examples, iPhone® and iPad® (iOS) SDKs, Android SDKs, and Android SDKs. TM We distribute software developer kits, including SDKs, BlackBerry® SDK, BREW SDK, Palm® OS SDK, Symbian SDK, webOS SDK, and Windows® Mobile SDK.

[0213] Those skilled in the art will recognize, in non-limiting embodiments, that several commercial forums are available for the distribution of mobile applications, including Apple® App Store, Google® Play, Chrome WebStore, BlackBerry® App World, App Store for Palm devices, App Catalog for webOS, Windows® Marketplace for mobile devices, Ovi Store for Nokia® devices, Samsung® Apps, and Nintendo® DSi Shop. (Standalone application)

[0214] In some embodiments, the computer program includes a standalone application, which is a program launched as an independent computer process, not an add-on to an existing process, such as a plug-in. Those skilled in the art will recognize that standalone applications are often compiled. A compiler is a computer program that translates source code written in a programming language into binary object code, such as assembly language or machine code. Suitable compiled programming languages, in non-limiting embodiments, include C, C++, Objective-C, COBOL, Delphi, Eiffel, Java®, Lisp, and Python. TM This includes Visual Basic and VB.NET, or a combination thereof. Compilation is often performed to create an at least partially executable program. In some embodiments, a computer program includes one or more executable compiled applications.

[0215] (Web browser plugin) In some embodiments, the computer program includes a web browser plugin (e.g., an extension, etc.). In computing, a plugin is one or more software components that add specific functionality to a larger software application. Software application makers support third-party developers in creating the ability to extend the application, easily add new features, and support plugins to reduce the size of the application. When supported, plugins enable customization of the functionality of a software application. For example, plugins are commonly used in web browsers to play videos, generate bi-directionality, perform virus scans, and display specific file types. Those skilled in the art will be familiar with some web browser plugins, including Adobe® Flash®, Microsoft® Silverlight®, and Apple® QuickTime®. In some embodiments, the toolbar comprises one or more web browser extensions, add-ins, or add-ons. In some embodiments, the toolbar comprises one or more explorer bars, toolbands, or deskbands.

[0216] In light of the disclosure provided herein, those skilled in the art will recognize that, as non-limiting examples, there are several plugin frameworks available that enable the development of plugins in various programming languages, including C++, Delphi, Java®, PHP, Python TM , and VB.NET, or combinations thereof.

[0217] A web browser (also called an internet browser) is a software application designed for use with a network-connected digital processing device to read, present, and traverse information resources on the World Wide Web. Preferred web browsers, in non-limiting embodiments, include Microsoft® Internet Explorer®, Mozilla® Firefox®, Google® Chrome, Apple® Safari®, Opera Software® Opera®, and KDE Konqueror. In some embodiments, a web browser is a mobile web browser. Mobile web browsers (also called microbrowsers, minibrowsers, and wireless browsers) are designed for use on mobile digital processing devices, in non-limiting embodiments, including handheld computers, tablet computers, netbooks, subnotebook computers, smartphones, music players, personal digital assistants (PDAs), and handheld video game systems. Suitable mobile web browsers, in non-exclusive examples, include the Google® Android® browser, the RIM BlackBerry® browser, Apple® Safari®, Palm® Blazer, Palm® WebOS® browser, Mozilla® Firefox® for mobile, Microsoft® Internet Explorer® Mobile, Amazon® Kindle® Basic Web, Nokia® browser, Opera Software® Opera® Mobile, and Sony® PSP TM Includes browsers.

[0218] (Software module) In some embodiments, the platforms, systems, media, and methods disclosed herein involve the use of software, servers, and / or database modules, or the same. In light of the disclosures provided herein, software modules are created using machines, software, and languages ​​known to those skilled in the art, and by techniques known to those skilled in the art. Software modules disclosed herein are implemented in numerous ways. In various embodiments, a software module comprises files, sections of code, programming objects, programming structures, or a combination thereof. In further various embodiments, a software module comprises multiple files, multiple sections of code, multiple programming objects, multiple programming structures, or a combination thereof. In various embodiments, one or more software modules comprise, in non-limiting embodiments, a web application, a mobile application, and a standalone application. In some embodiments, a software module resides within a single computer program or application. In other embodiments, a software module resides within two or more computer programs or applications. In some embodiments, a software module is hosted on a single machine. In other embodiments, a software module is hosted on two or more machines. In further embodiments, a software module is hosted on a cloud computing platform. In some embodiments, the software module is hosted on one or more machines in one location. In other embodiments, the software module is hosted on one or more machines in two or more locations.

[0219] (Database) In some embodiments, the platforms, systems, media, and methods disclosed herein include the use of one or more databases or identical ones. In light of the disclosures provided herein, those skilled in the art will recognize that many databases are suitable for storing and retrieving information. In various embodiments, suitable databases include, in non-limiting embodiments, relational databases, non-relational databases, object-oriented databases, object databases, entity-relational model databases, associative databases, and XML databases. Further non-limiting embodiments include SQL, PostgreSQL, MySQL, Oracle, DB2, and Sybase. In some embodiments, the database is internet-based. In further embodiments, the database is web-based. In yet further embodiments, the database is cloud computing-based. In other embodiments, the database is based on one or more local computer storage devices.

[0220] Figure 20A shows a schematic diagram of a handheld OCT system with an eye adapter. In some cases, the system comprises a body 2000. In some embodiments, the body features a surface adapted to provide an ergonomic grip of the system. In some cases, the surface adapted to provide an ergonomic grip comprises one or more finger restraints 2005. In some cases, the system further comprises a measuring end with an adapter 2010 configured to interface with the user's eye socket. In some embodiments, the system further comprises a detector that detects the orientation of the system and determines whether the user's left or right eye is being measured. In some cases, the system comprises a cap 2020. In some cases, the cap is used to cover the eye that is not being measured. For example, when the left eye is being measured, the cap covers the right eye. When the right eye is being measured, the cap covers the left eye. In some embodiments, when neither eye is being measured, the cap is positioned across the measuring end of the system to protect the system components from damage.

[0221] In some cases, the system includes an optical system 104 within the main unit. In some embodiments, the system includes a laser source 500. In some cases, the laser source directs laser light to a collimating lens 505. In some cases, the collimating lens shapes the laser source into a collimated beam of light. In some embodiments, the laser light is directed to a beam splitter 2030. In some cases, the beam splitter 2030 directs a portion of the laser light to an optical intensity meter 2035. In some cases, the optical intensity meter performs continuous measurements of the emitted laser intensity, enabling correction of the OCT signal based on the measured intensity or implementation of optical feedback techniques. In some embodiments, a portion of the light that passes through the beam splitter 2030 without being directed to the optical intensity meter collides with one or more beam splitters 510. In some cases, one or more beam splitters 510 direct a portion of the light to the user's eye and another portion to a reference mirror 530. In some cases, the reference mirror comprises a reference surface integrated into the main body of the system. In some embodiments, the system further includes a detector 542 for detecting the OCT signal.

[0222] In some embodiments, the system includes a battery 106. In some cases, the battery is a rechargeable battery. In other cases, the battery is a lithium-ion battery. In some embodiments, the battery is a nickel-metal hydride battery. In other cases, the battery is a nickel-cadmium battery. In other cases, the battery is operably coupled to a charging device 2040. In other cases, the charging device is a contiguated charging device. The charging device can be any contiguated charging device known to those skilled in the art. In other cases, the charging device is an inductively coupled charging device. The charging device can be any inductively coupled charging device known to those skilled in the art.

[0223] In one example, a wireless communication circuit and processor, as described herein, are coupled to a battery to power a miniature OCT system, collect OCT data, and transmit the data wirelessly.

[0224] In some cases, the system includes additional components to enable the user to operate the system correctly. In some embodiments, the system includes an orientation or motion sensor 2050. In some cases, the orientation or motion sensor includes a gyroscope for measuring the orientation of the device and determining the eye being measured. In some cases, the orientation or motion sensor includes an accelerometer for measuring the movement of the device. In some embodiments, the orientation or motion sensor includes any orientation or motion sensor known to those skilled in the art. In some cases, the system includes a fixation target 2060 that is visible when the miniature OCT system measures the retina. In some cases, the system includes mechanical features 2070 for providing electrical safety. In some embodiments, the system includes one or more status indicators 2080.

[0225] Figure 20B shows a handheld OCT system adapted to measure either the right or left eye. When operated to provide a right eye measurement, the handheld OCT system 100 operates in configuration 2020a, having an eye cap 2020 positioned to the left of the measuring end of the handheld OCT system. When operated to provide a left eye measurement, the handheld OCT system operates in configuration 2020b, having an eye cap positioned to the right of the measuring end of the handheld OCT system. When neither eye is being measured, the handheld OCT system operates in configuration 2020c, having an eye cap positioned to cover the measuring end of the handheld OCT system. In this configuration, the eye cap provides protection for the internal components of the handheld OCT system when the system is not in use. The eye cap transitions from configuration 2020a to configuration 2020b by a 180-degree rotation of the eye cap. In some cases, a handheld OCT system has a switch that detects the eye being examined using the OCT system.

[0226] Figure 20C shows a handheld OCT system with indicator lights and a power adapter. In some cases, the end of the handheld OCT device opposite the measuring end is equipped with one or more visual indicators 2080. In some embodiments, the visual indicator is equipped with a light source. In some cases, the light source is a light-emitting diode (LED). In some embodiments, the visual indicator is equipped with a first visual indicator 2082 for indicating whether the handheld OCT device is operating. In some embodiments, the visual indicator is equipped with a second visual indicator 2084 for indicating whether the handheld OCT device is utilizing battery power. In some cases, the visual indicator is equipped with a third visual indicator 2086 for indicating whether the handheld OCT device is utilizing an external power source. In some embodiments, the visual indicator is equipped with a fourth visual indicator 2088 for indicating whether the handheld OCT device is not suitable for use. In some embodiments, the end of the handheld OCT device opposite the measuring end is equipped with an adapter 2040 for receiving power.

[0227] Figure 20D shows a handheld OCT positioned close to the eye to provide OCT measurements. In some cases, the measuring end of the handheld OCT system is molded to conform to the orbit. In some embodiments, an eye cap is positioned to cover the eye that is not being measured. In some cases, the handheld OCT system directs light into the eye to acquire OCT measurements.

[0228] In some cases, a handheld OCT device is configured to acquire sufficient information to determine a single RT or RLT measurement within a time-frequency range that is merely associated with eye movements relative to the device. In some embodiments, eye movements relative to the device are due to the user's hand movements while holding the device. In some cases, eye movements relative to the device are due to eye movements. In some cases, a handheld OCT device is configured to acquire RT or RLT measurements within a period of 100 milliseconds, 50 milliseconds, or 10 milliseconds or less. In some cases, a handheld OCT device is configured to acquire RT or RLT measurements within a period that is within a range defined by any two of the aforementioned values.

[0229] Figure 21 shows a calibration kit for a handheld OCT device. In some cases, the handheld OCT device 100 is equipped with a calibration device 2100. In some embodiments, the calibration device is located on the inner surface of the cap 2020 in Figure 20.

[0230] Figure 22 shows a schematic diagram of the optical system of a sweep-source optical coherence tomography (SS-OCT) device utilizing a scanning mechanism, according to several embodiments. The optical system 102 comprises a light source 700 as described herein, a first beam splitter 710, and a reference mirror 730. A first processing unit 740 is coupled to a detector 742 to detect a sweep-source interference signal. The first processing unit may comprise a first photodetector 742 as described herein and a first signal processing unit 742 as described herein.

[0231] The optical system may further include a collimating optical element 2210. The collimating optical element may, for example, include a collimating lens. The collimating optical element may collimate light emitted from a light source prior to interaction of light with other optical elements. The optical system may further include a lens 2220 for focusing interference signals onto a photodetector 742. The optical system may further include a pinhole 2230 through which light focused by the first lens passes prior to detection by the first processing unit. The optical system may further include a neutral density filter 2240 for reducing the intensity of light incident on the reference mirror.

[0232] The optical system may further include a beam splitter 2250. The beam splitter may be any beam splitter as described herein. The second beam splitter may direct a portion of the light emitted by the light source to a second photodetector 2260 which may be analogous to the first processing unit 740, or to other circuits configured to control the amount of energy emitted by the VCSEL. The second processing unit may include a second photodetector (not shown) and a second signal processing unit (not shown), which may be analogous to the first photodetector and the first signal processing unit. The second processing unit may detect variations in the intensity of the light emitted by the light source. The detected variations in the intensity of the light emitted by the light source may be used to correct the SS-OCT signal detected by the first processing unit with respect to errors associated with the variations in the intensity of the light emitted by the light source. The optical system may further include a lens 2270 which focuses a portion of the light emitted by the light source onto the second photodetector 2260.

[0233] The light source 700 can be configured in many ways. For example, the light source 700 may comprise a sweep source VCSEL driven as described herein. Alternatively, or in combination, the VCSEL may be cooled to increase the sweep range. For example, the VCSEL may be cooled using a cooler such as a thermoelectric cooler to allow the VCSEL to be driven over a wider sweep range. The VCSEL may comprise a MEMS actuator coupled to a mirror to increase the sweep wavelength range to about 20 nm or greater. The VCSEL may also be coupled to an external mirror and an actuator for changing the mirror's position to increase the sweep wavelength range, for example. A VCSEL coupled to a movable mirror may be swept over a wavelength range in the range of about 10 to 30 nm or greater.

[0234] Table 2 shows the sweep range and resolution that can be obtained for a 10–30 nm sweep of the VCSEL in a compact SS-OCT system as described herein. [Table 2]

[0235] The light source 700 can be swept by an amount defined by any two values ​​in Tables 1 and 2, for example, over a range of 9 nm to 20 nm, to provide a corresponding resolution, for example, a corresponding resolution in the range of 35.4 μm to 15.9 μm.

[0236] In some embodiments, the miniature SS-OCT system may further include a scanning mechanism 2300. The scanning mechanism 2300 may comprise an actuator 2305 and a mirror 2310 deflected by the actuator to scan a light beam over the eye. The actuator 2305 may comprise any actuator known to those skilled in the art, such as a micro-electromechanical system (MEMS) actuator, a galvanometer, or a piezoelectric crystal. The scanning mechanism 2300 may be coupled to a control unit as described herein.

[0237] Figure 23A shows a scanning mechanism 2300 optically coupled to the eye with a compact SS-OCT system according to several embodiments. The scanning mechanism 2300 may comprise a telescope system comprising a first scanning optical element such as a mirror 2310 and a first telescope lens 2320 and a second telescope lens 2330. The telescope system may comprise, for example, a 4-f telescope system. The telescope system may further comprise a mirror 2325 for deflecting the light beam scanned toward the eye. The second telescope lens 2330 may comprise an aspherical lens.

[0238] In some embodiments, the mirror 2325 couples the optical path of the patient visualization system with the optical path of the scanned light beam. In some cases, the mirror 2325 is a short-path mirror. The patient visualization system may include a lens 2440, an aperture 2460, and a lens 2450, as further described in Figure 24.

[0239] The scanning optical element may comprise any type of scanning optical element known to those skilled in the art, such as a mirror, prism, polygonal mirror, or lens. The scanning element may be a galvanometer. The scanning element may enable RT or RLT measurements at two or more locations on the retina by scanning the measurement beam across multiple locations on the retina.

[0240] Figure 23B shows an array of retinal thickness (RT) or retinal layer thickness (RLT) measurement sites according to several embodiments. The scanning mechanism described herein can direct measurement light to multiple measurement sites 2350a, 2350b, 2350c, 2350d, 2350e, 2350f, 2350g, 2350h, 2350i, 2350j, 2350k, 2350l, 2350m, 2350n, 2350o, 2350p, 2350q, 2350r, 2350s, 2350t, 2350u, 2350v, 2350w, 2350x, and 2350y on the retina 2340. While 25 measurement locations are depicted, the scanning mechanism may direct the measurement light to two or more measurement locations, five or more measurement locations, 10 or more measurement locations, 20 or more measurement locations, 50 or more measurement locations, 100 or more measurement locations, 200 or more measurement locations, 500 or more measurement locations, or 1,000 or more measurement locations. RT or RLT measurements may be taken at each measurement location to obtain multiple RT or RLT measurements. Multiple RT or RLT measurements may enable the construction of a spatial map of RT or RLT measurements. Multiple RT or RLT measurements may span a first distance on the retina in a first direction and a second distance on the retina in a second direction traversing the first direction. The first distance may have lengths of less than 0.5 mm, less than 1.0 mm, less than 1.5 mm, less than 2.0 mm, less than 2.5 mm, less than 3.0 mm, less than 3.5 mm, less than 4.0 mm, less than 4.5 mm, or less than 5.0 mm. The second distance may have lengths of less than 0.5 mm, less than 1.0 mm, less than 1.5 mm, less than 2.0 mm, less than 2.5 mm, less than 3.0 mm, less than 3.5 mm, less than 4.0 mm, less than 4.5 mm, or less than 5.0 mm.

[0241] Figure 24 shows a schematic diagram of the optical system of a compact swept-source optical coherence tomography (SS-OCT) device equipped with a patient visualization system 2400. The patient visualization system 2400 may include a camera for visualizing the fundus and a display for measuring patient visual acuity. The display for measuring patient visual acuity may be configured, for example, to allow the patient to gaze at a visual target by displaying a small object that is visible to the patient. The optical system 102 may include a light source 700 as described herein, a collimating optical element 2210, a first beam splitter 710, a reference mirror 730, and a first lens 2200 coupled to a photodetector 742.

[0242] The optical system may further include a scanning mechanism as described herein. The scanning mechanism may include a scanning optical element 2310 and a telescope system comprising a first telescope lens 2320 and a second telescope lens 2330. The optical system may further include a mirror 2435, such as a hot mirror. The hot mirror may be configured to reflect infrared light. The hot mirror may be configured to transmit visible light. The hot mirror may be configured to reflect OCT measurement light to the eye and transmit visible light to the patient in order to display an image shown on a display and to image the fundus using a detector.

[0243] The visual function measurement device of a compact SS-OCT system may include a Badal lens and imaging system for compensating for the patient's refractive error. The lens 2450 may be coupled to an actuator to move the lens along the optical axis to correct the refractive error of the object, focusing the image of the fundus on the detector array and then focusing the image on a display as seen by the object. The Badal lens may be configured to provide a virtual image seen by the patient at a constant viewing angle, and the lens may provide refractive error compensation that is linear with microdisplay displacement (e.g., ±5 diopters).

[0244] The visual function measurement device presents the patient with one or more visual cues.

[0245] The compact SS-OCT system may further include one or more camera devices, such as a fundus camera. The compact SS-OCT system may include a visual camera device configured, for example, to measure the anterior portion of the eye. The optical system coupled to the fundus camera and the visual display may include a telescope comprising a first telescope lens 2440 and a second telescope lens 2450. The optical system may further include an aperture 2460 with a stopper. The stopper may be, for example, a ring stopper. The optical system may further include a second beam splitter 2470. The second beam splitter may direct a portion of the light incident from the eye toward a detector array 2480 and a portion of the light incident from the microdisplay 2490 toward the eye for patient visualization. The detector array may be a charge-coupled device (CCD). The detector array may be, for example, a complementary metal-oxide-semiconductor (CMOS) detector array.

[0246] A visual camera device may acquire an image of the eye, while the OCT system acquires RT or RLT measurements of the eye. The visual camera device may acquire an image of the eye before, during, or after the OCT system acquires RT or RLT measurements of the eye as described herein. A fundus camera device may acquire an image of the fundus, while the OCT system acquires RT or RLT measurements of the eye. The fundus camera device may acquire an image of the eye before, during, or after the OCT system acquires RT or RLT measurements of the eye. The fundus images acquired by the fundus camera device are processed to determine whether and by how much the OCT measurement location has moved between two consecutive measurements (due to voluntary or involuntary movements of the eye, or voluntary or involuntary movements of the handheld OCT system). The scanning of the OCT beam may be adjusted in response to eye movements to compensate for eye movements.

[0247] Figure 25 shows a method 2500 for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to several embodiments. Method 2500 includes the steps of: reading data; performing noise reduction on the read data; performing chirp correction on the read data; performing frequency analysis on the read data to obtain estimated frequencies; converting the estimated frequencies into retinal thickness; processing information from multiple estimators; and processing multiple measurement points.

[0248] In step 2502, the OCT data acquired by the OCT measurement system is read to form the read data. In some cases, the read data includes OCT interference intensity.

[0249] In step 2504, noise reduction is performed on the read data.

[0250] In step 2506, chirp correction is performed on the read data. Chirp correction may include a step of resampling the OCT signal in the time domain. The step of resampling the OCT signal may convert a linear time signal into a linear wave vector signal. The resampling step may compensate for phase instability caused by the nonlinearity of the relationship between the wavelength of light emitted by the VCSEL or other light source and the driving current of the VCSEL or other light source, temperature fluctuations, aging of optical components, vibration, or other environmental conditions. The resampling step may be based on phase measurement of the light source, such as a phase measurement method as described herein. The resampling step may be performed during post-processing of the SS-OCT signal as described herein.

[0251] The resampling step may include first and second correction operations. In the first correction operation, the resampling step may correct the average nonlinearity of the phase of light emitted by a VCSEL or other light source based on the average behavior of light emitted by the light source over a period of time. In the second correction operation, the resampling step may correct deviations from the average behavior of the light source. The second correction operation is obtained based on the simultaneous acquisition of the phase signal and the SS-OCT signal and can therefore correct variations associated with changes in temperature, humidity, degradation of optical or electronic components, and other sources of drift in the SS-OCT signal.

[0252] In step 2508, frequency analysis is performed on the read data to obtain estimated frequencies. Frequency analysis may be performed using one or more estimators. Frequencies may be obtained using one, two, three, four, five, or more than five estimators. Estimators may utilize eigenspace techniques. Estimators may utilize eigendecomposition techniques. Estimators may utilize Pisarenko decomposition techniques. Estimators may utilize multiple signal classification (MUSIC) techniques. Each of the one or more estimators may utilize the MUSIC technique with a unique filter. Each estimator may obtain estimated frequencies from the read OCT data.

[0253] In step 2510, one or more estimated frequencies are used to determine the estimated RT or RLT. RT or RLT may be obtained from the analysis of terms in the interference signal. The terms used to determine RT or RLT may consist of automatic or crossed terms in the interference signal, and combinations thereof. Automatic terms may be generated by back-reflected signals from a sample (e.g., retina or retinal layers) independently of the reference term of the SS-OCT system. Automatic terms may correspond to a single frequency at a relatively low frequency. The frequency associated with the automatic term may directly relate to RT or RLT. RT or RLT may be obtained from the analysis of crossed terms in the interference signal. Crossed terms may be generated by back-reflected signals from the sample and the reference mirror. Crossed terms may correspond to a pair of frequencies at a relatively high frequency. The difference between the two frequencies of the pair may directly relate to RT or RLT. The terms may be combined to determine the thickness of the retina, the thickness of multiple layers, and the relative locations of each of the multiple layers of the retina.

[0254] Alternatively, or in combination, RT or RLT may be obtained from an analysis of the envelope of the OCT signal in the time domain. The envelope of the OCT signal can be computed by performing mathematical transformations such as the Hilbert transform on the OCT signal. The envelope may undergo filtering operations to obtain a filtered envelope. RT or RLT may relate to the beat frequency of the filtered envelope. Estimation of RT or RLT using the envelope of the OCT signal may be less susceptible to noise, such as that associated with the motion (of the SS-OCT device or the user of the SS-OCT device).

[0255] In step 2512, information from multiple estimators is processed. Processing of multiple estimators may utilize statistical analysis procedures. Processing of multiple estimators may also utilize, for example, artificial intelligence or machine learning procedures.

[0256] In step 2514, multiple measurement points are processed. Multiple measurement points may be processed from multiple measurements taken at a single point on the retina. Multiple measurement points may be processed from measurements taken at multiple locations on the retina.

[0257] Figure 25 shows a method 2500 for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to several embodiments, but those skilled in the art will recognize many variations and adaptations. For example, some of the steps may be deleted, some of the steps may be repeated, and some of the steps may include substeps. The steps may be performed in different orders, for example.

[0258] Figure 26 shows schematic diagrams of SS-OCT devices incorporating a visual function measurement device according to several embodiments. The system may be sized for the patient to lift, for example, it may have sufficient weight to allow the patient to lift the system for measurement. The system may include a patient visualization system 2400, and the optical components may be arranged to provide a small system that can be held by the patient during measurement, for example. The system may include a display 2490, and may include a fundus camera as described herein. Light from a light source 700 may be directed toward a mirror 710, which divides the light into a measurement section directed toward the eye 750 and a reference section directed toward a reference mirror 730. The reference mirror 730 may be coupled to an optical detector 2660, which can detect a portion of the light transmitted by the reference mirror. The optical detector 2660 may measure fluctuations in the light output from the light source. The reference mirror 730 may be coupled to an actuator (not shown) to adjust the distance of the reference mirror and compensate for the fluctuating distance from the patient to the retina of the object in contact with the structure. The reference section may include mirrors for deflecting the beam. The reference mirror may consist of multiple mirrors, such as a mirror pair 2650. The location of the mirror pair 2650 may be adjusted to adjust the optical path length of the reference section. For example, an actuator may be coupled to the mirror pair 2650 to adjust the mirrors in a trombone configuration to adjust the optical path length of the reference section.

[0259] The scanning mechanism 2300 can scan the measurement beam, receive light from the retina, and direct the light towards the retina in a confocal configuration as described herein.

[0260] Figure 34 shows schematic diagrams of the optical system of an SS-OCT device incorporating a fixation target device and a fundus imaging device according to several embodiments.

[0261] The optical system may include an RT or RLT path comprising an interferometer as described herein. The interferometer may include a light source 700 as described herein. The light source may direct light to an optional collimating lens 2210 and a beam splitter 710 as described herein. The beam splitter may direct a first portion of light incident on the beam splitter along the reference arm of a reference mirror 730 and a second portion of light incident on the beam splitter along the reference arm of the interferometer as described herein. The second portion of light may be directed to an optional filter (such as a band-pass filter) 3470 and a scanning mirror 2310 or other scanning mechanism as described herein. The scanning mirror may direct the second portion of light to a telescope system comprising a first telescope lens 2320 and a second telescope lens 2330 as described herein. The telescope system may further include a mirror 2325 for deflecting the scanning light, which is deflected toward the eye 750 by the scanning mirror, as described herein. The scanning light may be reflected from the eye, retina, or one or more layers of the retina and directed backward along a path comprising elements 2330, 2325, 2320, 2310, 3470, and 710, as described herein. The scanning light may then be passed by a beam splitter 710 to an optional focusing lens 2220 and a detector 740, as described herein. The detector may detect interference between the scanning light that has passed through the measuring arm of the interferometer and the reference light that has passed through the reference arm of the interferometer, as described herein.

[0262] The optical system may include a visual target path. The visual target path may include a visual target light source 3450. The visual target light source may include a light-emitting diode (LED). The LED may emit light having a wavelength within the visible portion of the electromagnetic spectrum. For example, the LED may emit light having a wavelength in the range of 400 nm to 700 nm. The LED may emit approximately green light. For example, the LED may emit light having a wavelength of about 525 nm. The LED may emit light having multiple wavelengths within the visible portion of the electromagnetic spectrum. The visual target light source may direct the light toward an aperture 3455 which includes a stopper. The stopper may include, for example, a ring stopper. The light may then pass to a diffuser 3460. The light may then pass to a collimating lens 2450 and a stopper 2460 as described herein. The light may be directed toward a hot mirror 3435. A hot mirror may be configured to allow light to pass from the visual target path to lens 2440, as described herein. The light may then pass to beam splitter 2470, as described herein. The beam splitter may allow the visual target light to pass to eye 750. The light may be detected by the eye and provide a target for the user to focus on. Focusing on a target may allow the user to reduce eye movement during fundus, RT, or RLT measurements. In some cases, the beam splitter may allow the visual target light to pass through mirror 2325 and a second telescopic lens 2330 to the eye, as described herein. The beam splitter 2470 may be configured to direct a portion of the visual target light to detector 2480. The portion of the visual target light directed to the detector may allow the light intensity delivered to the eye to be monitored over time.

[0263] The optical system may further include a fundus illumination path. The fundus illumination path may include a fundus illumination light source. The fundus illumination light source may include an LED. The LED may emit light having a wavelength within the near-infrared portion of the electromagnetic spectrum. For example, the LED may emit light having a wavelength in the range of 700 nm to 2,500 nm. For example, the LED may emit light having a wavelength of approximately 780 nm. The LED may emit light at multiple wavelengths within the near-infrared portion of the electromagnetic spectrum. The fundus illumination light source may direct the light toward an aperture 3415 which is equipped with a stopper. The stopper may include, for example, a ring stopper. The light may then pass to a diffuser 3420. The light may then pass to a collimating lens 3425. The light may then pass to a first polarizer 3430. The first polarizer may be a linear polarizer. The first polarizer may impart linear polarization to the light. The first polarizer may be an s-polarizer. A first polarizer may impart s-polarization to the light. The first polarizer may be a p-polarizer. The light may then pass to a beam splitter 2470 as described herein. The beam splitter may allow the fundus illumination light to pass to the eye 750. In some cases, the beam splitter may allow the fundus illumination light to pass to the eye through a mirror 2325 and a second telescopic lens 2330 as described herein. The beam splitter 2470 may be configured to direct a portion of the fundus illumination light to a detector 2480. The portion of the fundus illumination light directed to the detector may allow the light intensity delivered to the eye to be monitored over time.

[0264] The optical system may further include a fundus imaging target path. The fundus imaging target path may receive fundus illumination light reflected from the eye. The light may be directed through elements 2330, 2325, 2470, 2440, and 3435. The hot mirror 3435 may be configured to direct the light to a second polarizer 3440. The second polarizer may be configured to allow light having polarization similar to that imparted by the first polarizer to pass through. The light may be directed to an imaging lens 3445 and a camera 2490, as described herein.

[0265] The imaging lens and camera may record one or more images of the user's eye fundus. The imaging lens and camera may be configured to record a series of images of the user's eye fundus. The camera may be coupled to an image processor. The image processor may be configured to recognize the fundus. For example, the image processor may be configured to detect veins in the fundus. The image processor may be configured to detect veins in the fundus by comparing an image of the fundus with a template. The template may consist of a small region of the eye image containing veins. The image processor may be configured to detect tubular structures of the diameter of veins. For example, the image processor may be configured to detect veins by implementing a filter such as a Hessian multiscale filter. The filter may enhance the clarity of the region of the fundus image containing veins and the region of the template containing veins. The image processor may cross-correlate the enhanced region of the fundus image with the enhanced region of the template. In this way, the location of the veins may be determined. The location of the veins may be determined for each fundus image in a series of fundus images. In this way, the relative movement of the eye may be measured over time.

[0266] Figure 35 shows a schematic diagram 3500 of an electronic circuit for controlling the optical system of a compact SS-OCT system described herein. The optical system described herein may be coupled to an electronic circuit configured to control the operation of various elements of the optical system. For example, the photodetector 740 described herein may be electronically coupled to a first filter 3510, such as a low-pass filter. The first filter may be configured to receive the interference signal described herein from the photodetector, filter the interference signal, and pass the filtered interference signal to a data acquisition module 3580. The data acquisition module may include a data acquisition card, such as a data acquisition card provided by National Instruments. The data acquisition module may include one or more analog-to-digital converters (ADCs) or one or more digital-to-analog converters (DACs). The data acquisition module may be configured to sample the ADC at a sampling rate of at least 1 kilosample per second (kS / sec), at least 2 kS / sec, at least 5 kS / sec, at least 10 kS / sec, at least 20 kS / sec, at least 50 kS / sec, at least 100 kS / sec, at least 200 kS / sec, at least 500 kS / sec, at least 1,000 kS / sec, at least 2,000 kS / sec, at least 5,000 kS / sec, or at least 10,000 kS / sec. The data acquisition module may be configured to sample the ADC at a sampling rate within the range defined by any two of the aforementioned values. The data acquisition module may be configured to sample the DAC at a sampling rate of at least 1 kilosample per second, at least 2 kS / second, at least 5 kS / second, at least 10 kS / second, at least 20 kS / second, at least 50 kS / second, at least 100 kS / second, at least 200 kS / second, at least 500 kS / second, at least 1,000 kS / second, at least 2,000 kS / second, at least 5,000 kS / second, or at least 10,000 kS / second. The data acquisition module may be configured to sample the DAC at a sampling rate within the range defined by any two of the aforementioned values.

[0267] (For example, with respect to Figure 36) The interferometer device 3640 for enhancing phase stability as described herein may be electronically coupled to a second filter 3520, such as a low-pass filter. The second filter may be configured to receive phase measurements from the interferometer device 3640, filter the phase measurements, and pass the filtered phase measurements to a data acquisition module, as described herein.

[0268] The electronic circuit may include a safety circuit. The electronic circuit may include a first safety circuit 3530 electronically coupled to the data acquisition module. The first safety circuit may be configured to receive a first status signal from the data acquisition module. The first safety circuit may be configured to monitor a signal from the interferometer device 3640. If the signal from the interferometer device 3640 exceeds a safety level, the first safety circuit may transmit a signal to activate a first safety device 3570, such as a shutter. Activation of the first safety device may reduce the amount of light intensity received by the interferometer device 3640 or the target eye to a safe level. When the first safety device is activated, the first safety circuit may transmit a status signal to the data acquisition module. This status signal may be passed to the operator of the SS-OCT device to ensure that the operator is informed of the safety status.

[0269] The electronic circuit may include a second safety circuit 3540 electronically coupled to the data acquisition module. The second safety circuit may be configured to receive a second status signal from the data acquisition module. The second safety circuit may be configured to monitor signals from a light source driver 3550, such as a VCSEL driver. If the output intensity from the light source driver exceeds a safe level, the second safety circuit may transmit a signal to shut down the light source driver or otherwise reduce the power supplied by the light source driver. Shutting down or reducing the power from the light source driver can reduce the amount of light intensity supplied by the light source to a safe level. The data acquisition module 3580 may be configured to transmit a modulation signal to the light source driver to modulate the operating current of the light source as described herein.

[0270] The data acquisition module 3580 may be electronically coupled to the fundus camera 2490 as described herein. The data acquisition module may be configured to trigger measurements from the fundus camera. Signals from the fundus camera may be directed to the calculation module 3585. The calculation module may include an external computer. The calculation module may include a personal computer or workstation. The calculation module may include a mobile device such as a tablet or smartphone. The calculation module may be configured to run a visualization program such as a graphical user device (GUI). The calculation module may be configured to receive one or more fundus images from the fundus camera. The calculation module may be configured to display one or more fundus images on the display 3595. The display may be external to the calculation module, such as an external monitor electronically coupled to the calculation module. The display may be integrated into the calculation module, as may be the case for a calculation module configured as a mobile device.

[0271] The calculation module may be electronically coupled to the control bus module 3590. The control bus module may include a Universal Serial Bus (USB) hub. The calculation module may direct signals to the control bus module 3590 to control the operation of one or more optical components of the miniature SS-OCT system. For example, the control bus module may direct signals to a scanner interface module 3560 that controls the operation of the scanning element 2310 described herein. The scanner interface module may include a high-voltage driver that supplies power to the scanning element at a high voltage, such as up to 200V. The control bus module may direct signals to a first OCT focusing element, such as one of the lenses 2330, 3650, or 3655 described herein, to adjust the focus of the SS-OCT system described herein. The control bus module may direct signals to a second OCT focusing element, such as one of the lenses 2320, 3650, or 3655 described herein, to adjust the focus of the SS-OCT system described herein. The first or second focusing element may include a tunable lens. Alternatively, or in combination, the first or second focusing element may include a movable lens. A control bus module may direct signals to a live view camera. The live view camera may provide one or more images of the eye. The live view camera may provide one or more images of a lateral view of the eye. Images acquired by the live view camera may assist the operator of the SS-OCT device described herein in correctly aligning the device with the target eye. For example, images acquired by the live view camera may allow the operator to select an appropriate distance between the eye and the SS-OCT device.

[0272] Although not shown in Figure 35, the electronic circuitry may be configured to control other elements of the miniature SS-OCT system described herein. For example, the electronic circuitry may be configured to control any or all of the optical elements described herein with respect to any of Figures 5, 6A, 7A, 8A, 8B, 22, 23A, 24, 26, 34, or 36. The calculation module 3585 may be configured to implement any step of any method described herein, such as method 1100, 1200, or 2500.

[0273] Figure 36 shows a schematic diagram of the optical system of an SS-OCT device incorporating an interferometer to enhance phase stability. The optical system may comprise a light source 700, a collimating lens 2210, a beam splitter 710, a reference mirror 730, a scanning mirror 2310, telescope lenses 2320 and 2330, a mirror 2325, a focusing lens 2220, and a detector 740, as described herein. Elements 700, 2210, 710, 730, 2310, 2320, 2330, 2325, 2220, and the detector 740 may be arranged to generate an OCT signal from the eye 750, as described herein.

[0274] The optical system may have an aperture 2460, which includes a stopper. The stopper may be, for example, a ring stopper. The stopper may be located between the collimating lens 2210 and the first coupling lens 3620. The first coupling lens may be a fiber coupling lens. The first coupling lens may have a numerical aperture sufficient to direct the collimated light radiated into the optical fiber by the light source. The first coupling lens may be configured to direct the light towards the interferometer device 3640.

[0275] The interferometer may be a fiber-based interferometer. Alternatively, the interferometer may be a bulk interferometer. The interferometer may be configured to direct a first portion of the light (e.g., 95% of the light) to a second coupling lens 3630 and a second portion of the light (e.g., 5% of the light) to an optical analysis unit within the interferometer. The optical analysis unit may direct a third portion of the light (e.g., 50% of the second portion of the light) to an intensity monitor within the interferometer and a fourth portion of the light (e.g., 50% of the second portion of the light) to a Mach-Zehnder interferometer. The intensity monitor measures the light intensity of the light incident on the interferometer and may output the measurement to an intensity measurement output 3642. Such a measurement enables monitoring and ensures that the light intensity does not exceed a safe level. The Mach-Zehnder interferometer measures the phase of the light coupled into the interferometer and may output the measurement to a phase measurement output 3644. Phase can be monitored, and phase drift (such as phase drift associated with ambient temperature fluctuations, aging of optical components, transient responses of optical or electronic components, or other factors) can be corrected. Correcting phase drift can narrow the peak in the frequency domain, which can increase the accuracy of RT or RLT estimations.

[0276] Phase measurements may be acquired by a Mach-Zehnder interferometer, as described herein. Alternatively, or in combination, phase measurements may be acquired using another optical phase measuring device, such as a Fabry-Perot cavity. The phase of the light source may be acquired simultaneously with the OCT signal.

[0277] The second coupling lens may be a fiber coupling lens. The second coupling lens may have a numerical aperture sufficient to receive the light emitted by the interferometer and direct the light to the first and second tunable lenses 3650 and 3655 and the focusing lens 3660. The first and second tunable lenses may be configured to vary the spot size of the light emitted onto the retina by the SS-OCT system.

[0278] The optical system may further include a beam expander comprising first and second beam expander lenses 3665 and 3670.

[0279] Figure 27A shows a dark visual cue on a bright background. The visual cue may be presented individually or in combination. The visual cue may include a letter in an orientation, such as a rotating E. The subject may input the orientation of the letter to determine the visual acuity of the cue. The visual cue may include multiple dark letters 2710a, 2710b, 2710c, and 2710d, such as the letter "E," on a bright background 2700. Although four letters are shown, the visual cue may include one, two, three, four, five, six, seven, eight, nine, ten, or more than ten letters. The letters may move along the background, such as downwards. Other visual stimuli, such as arrows, may be presented to indicate the orientation of the letters to the patient.

[0280] Figure 27B shows a dark visual cue on a dark background. The visual cue may consist of multiple dark letters 2710a, 2710b, 2710c, and 2710d, such as the letter "E", on a dark background 2720. Although four letters are shown, the visual cue may consist of one, two, three, four, five, six, seven, eight, nine, ten, or more than ten letters. The letters may move along the background, such as downwards. The letters may be presented in different orientations, such as facing left, right, up, or down.

[0281] In many embodiments, visual cues are displayed on a display as described herein, and lenses may compensate for refractive errors of an object in order to examine the object's vision. A compact SS-OCT system may include an input for the patient to input the orientation of presented characters so that the patient's vision can be determined. The input may include an input configured to receive the orientation of characters such as a button or a set of buttons.

[0282] Figure 28A shows a schematic diagram of a housing for an exemplary handheld monocular OCT system according to several embodiments. The left side of the figure shows a side view 2800 of the housing. The housing may comprise a body 2810. The body of the housing may comprise a handle 2850 for the patient to grasp the system. The body 2810 may be coupled to an eyepiece 2805, or a structure for contact with the patient, such as foam or other structure. The housing may have an internal volume containing any of the components of the handheld OCT systems and devices described herein. The reference section of the interferometer may extend, for example, at least partially into the handle 2850.

[0283] The eyepiece may be configured to dock with the area surrounding the target's eye, such as the skin surrounding the eye. The main body may be configured to be held in the target's hand.

[0284] The right side of the figure shows a front view 2820 of the housing. The eyepiece may comprise an area 2825 configured to dock with an area surrounding the eye of the subject, and an aperture 2830 configured to allow OCT measurement light to travel from the OCT system to the eye and back. The aperture may further comprise a mechanism 2835 that allows the subject to indicate the orientation of each letter presented to it (e.g., left, right, up, or down).

[0285] Figure 28B shows a housing for an exemplary handheld monocular OCT system according to several embodiments.

[0286] Figures 29A and 29B show the configuration of a handheld binocular OCT system according to several embodiments. Alternatively, the system may comprise a monocular system in which the eye not being measured is closed by the measurement system. The left side of the figure shows a side view 2900 of the housing. The housing may comprise eyepieces 2905a and 2905b and a body 2910. The housing may have an internal volume containing any of the components of the handheld OCT systems and devices described herein. The eyepieces may be configured to dock the housing to an area surrounding the subject's eye, such as the skin surrounding the subject's eye. The body may be configured to be held in the subject's hands.

[0287] The right side of the figure shows a front view 2920 of the housing. The eyepiece may comprise areas 2925a and 2925b configured to dock with an area surrounding the eye of the subject, and an aperture 2930 configured to allow OCT measurement light to travel from the OCT system to one or both of the eyes and back. The aperture may further comprise a mechanism 2935 that allows the subject to present a visual cue (such as one or more of the letters "E") to the subject, as described herein. The housing may comprise a mechanism 2935 that allows the subject to indicate the orientation of each letter presented to it (such as left, right, up, or down).

[0288] Figure 29C shows the configuration of an exemplary handheld binocular OCT system according to several embodiments.

[0289] Figure 30 shows the configuration of an exemplary handheld binocular OCT system according to several embodiments. The housing 3000 may comprise eyepieces 3005a and 3005b and a body 3020. The housing may have an internal volume containing any of the components of the handheld OCT systems and devices described herein. The eyepieces may be configured to dock the housing to an area surrounding the subject's eye, such as skin surrounding the subject's eye. The body may be configured to be held in the subject's hands. One of the eyepieces may have an aperture 3010 configured to allow OCT measurement light to travel from the OCT system to one eye and back. The aperture may further be configured to present a visual cue (such as one or more letters "E") to the subject, as described herein. The housing may include a mechanism 3015 that allows the subject to indicate the orientation of each letter presented to them (such as left, right, up, or down). The body of the housing may have a cutout area. The orientation of the cutout area may indicate the eye being measured using an OCT system. The cutout area may be located on the opposite side of the housing from the eye being measured.

[0290] Orientation sensors, such as accelerometers, can be mechanically coupled to an optical system and electronically coupled to a control unit, as described herein, for measuring an eye measured in response to the orientation of the orientation sensor.

[0291] Figure 31A shows a handheld binocular OCT system directed to measure the subject's left eye.

[0292] Figure 31B shows an exemplary housing for a handheld binocular OCT system directed to measure the subject's right eye.

[0293] Figure 32A shows a VCSEL coupled to a cooler to increase the wavelength range swept by the VCSEL, according to several embodiments. The VCSEL in the SS-OCT system described herein may undergo a cooling procedure to reduce the operating temperature of the VCSEL to a temperature below the ambient temperature of about 37°C in order to increase the wavelength range swept by the VCSEL. Cooling can be combined with overdriving of the VCSEL, as described herein, to further increase the wavelength range swept by the VCSEL. The VCSEL in the SS-OCT system may be cooled to a temperature below the ambient temperature by 10°C, 20°C, 30°C, 40°C, 50°C, 70°C, 80°C, 90°C, or more. The VCSEL in the SS-OCT system may be cooled by an amount within the range defined by any two of the aforementioned values, for example, by an amount within the range of 20°C to 70°C. The swept wavelength range may be increased by 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or by an amount within the range defined by any two of the aforementioned values. For example, a VCSEL with a specified wavelength sweep range of 5 nm can be overdriven to increase the sweep range by about 3 nm, then cooled to increase the sweep range by about 2 nm, and finally provide a full sweep range of about 10 nm. The cooler can be configured in many ways and may include a Peltier cooler, a gas-based cooler, a chamber containing a gas such as nitrogen that expands to cool the VCSEL, or a cooled circulating fluid, or a combination thereof. The cooler may include, for example, a heat sink coupled to the VSCEL.

[0294] Figure 32B shows a schematic diagram 3200 of a VCSEL coupled to a thermoelectric cooler. The VCSEL 700 may be mounted on a VCSEL driver 3210. The VCSEL driver may comprise a printed circuit board (PCB). The VCSEL may be mounted on the VCSEL driver through one or more electrical connectors, such as electrical connectors 3260a and 3260b. The VCSEL or VCSEL driver may be coupled to a heatsink 3220 configured to extract heat from the VCSEL or VCSEL driver. The VCSEL may further be coupled to a thermoelectric cooler (TEC) 3230. The TEC may comprise a Peltier cooler. The TEC may be configured to cool the VCSEL to 10°C, 20°C, 30°C, 40°C, 50°C, 70°C, 80°C, 90°C, or above. The TEC may be configured to cool the VCSEL by an amount within the range defined by any two of the aforementioned values. The VCSEL may further be coupled to a temperature sensor 3240. The temperature sensor may comprise a thermistor. A temperature sensor may be configured to measure the operating temperature of the VCSEL. The temperature sensor and TEC may be coupled to a TEC controller 3250. The TEC controller may control the cooling force of the TEC based on the temperature of the VCSEL measured by the temperature sensor. In this way, the TEC, thermistor, and TEC controller may form a negative feedback system designed to maintain the VCSEL at a stable operating temperature, such as the operating temperature described herein.

[0295] Figure 33A shows a miniature SS-OCT system as described herein, mounted on a support such as a desktop support. The miniature SS-OCT system 100 may be any miniature SS-OCT system as described herein. The miniature SS-OCT system may have any of the capabilities described herein. For example, the miniature SS-OCT system may include an OCT imaging system, an eye-tracking system, a fixation target, or a Badal lens, as described herein. The miniature SS-OCT system may include one or two eyepieces.

[0296] The miniature SS-OCT system may be installed on a support system 3300, for example, removably mounted or attached to a support. The miniature SS-OCT system may be fixedly mounted to the support system. The miniature SS-OCT system may be removablely attached to the support system. The support system may be mounted on a tabletop or other surface. The support system 3300 may include a base 3310. The base may be mounted on or placed on a tabletop or other surface. The base may be fixedly mounted on a tabletop or other surface. The base may be removablely attached to a tabletop or other surface.

[0297] The support system may further include a mounting surface 3320 for receiving a miniature SS-OCT system. The mounting surface may be a mounting plate. The mounting surface may provide a location on which the miniature SS-OCT can be mounted. The mounting surface may be coupled to a base by a first coupling 3330. The first coupling may be configured to allow a user to change the distance between the mounting surface and the base, as indicated by the arrow labeled "1" in Figure 33A. The distance between the mounting surface and the base may be adjustable to only 1 cm, 2 cm, 5 cm, 10 cm, 20 cm, or 50 cm. The distance between the mounting surface and the base may be adjustable to a value within the range defined by any two of the aforementioned values. The distance between the mounting surface and the base may be adjusted to increase user comfort while using the miniature SS-OCT system.

[0298] The support system may include a second coupling configured to allow the user to change the angle between the mounting surface and the base, as indicated by the arrow labeled "2" in Figure 33A. The angle between the mounting surface and the base may be adjustable by only 1 degree, 2 degrees, 5 degrees, 10 degrees, 20 degrees, 50 degrees, or 100 degrees. The angle between the mounting surface and the base may be adjustable only by a value within the range defined by any two of the aforementioned values. The angle between the mounting surface and the base may be adjusted to increase user comfort while using the miniature SS-OCT system.

[0299] The support system may further include a chin rest 3340. The chin rest may provide a place for the user to rest their chin while operating the miniature SS-OCT system. The chin rest may be coupled to the mounting plate by an extension 3350. The support system may include a third coupling configured to allow the user to change the distance between the chin rest and the eyepiece, as indicated by the arrow labeled "3" in Figure 33A. The distance between the chin rest and the eyepiece may be adjustable by a distance of 1 cm, 2 cm, 5 cm, or 10 cm. The distance between the chin rest and the eyepiece may be adjustable by a value within the range defined by any two of the aforementioned values. The distance between the chin rest and the mounting surface may be adjusted to increase user comfort while using the miniature SS-OCT system. The distance between the chin rest and the mounting surface may be adjusted to align the user's eye with the eyepiece of the miniature SS-OCT system. For example, the distance between the chin rest, the eyepiece, and the mounting surface can be adjusted to align the user's eye with the optical axis of the miniature SS-OCT system.

[0300] A small SS-OCT system mounted on a support may have length, width, and height. The length may be the longest dimension traversing the system, the width may be the next longest dimension traversing the system, and the width may be the shortest dimension traversing the system. The length, width, and height may traverse each other, for example, perpendicular to each other. A small SS-OCT system may have a length of 10 cm, 20 cm, or 50 cm. A small SS-OCT system may have a length that is within the range defined by any two of the aforementioned values. A small SS-OCT system may have a width of 5 cm, 10 cm, or 25 cm. A small SS-OCT system may have a width that is within the range defined by any two of the aforementioned values. A small SS-OCT system may have a height of 2.5 cm, 5 cm, or 10 cm. A small SS-OCT system may have a height that is within the range defined by any two of the aforementioned values.

[0301] The small SS-OCT system mounted on the support may have a mass of 0.1 kg, 0.2 kg, 0.5 kg, 1 kg, or 2 kg. The support system may have a mass within the range defined by any two of the aforementioned values.

[0302] Figure 33B shows a user using a desktop-mounted SS-OCT device. [Examples]

[0303] (Example 1) Detection limits for RT or RLT measurement Figure 14 shows an optical setup for determining the detection limit for measuring changes in RT or RLT using an SS-OCT system that utilizes a single VCSEL and does not use a reference arm. The setup comprises a VCSEL (V), a photodetector (P), a collimating lens (L1), a beam splitter (BS), a lens for focusing light onto the photodetector (L2), a lens for focusing light onto the sample (L3), a 22 mm long cylinder made of polymethyl methacrylate (PMMA), refractive index matching oil with a refractive index of 1.5120, two 150 μm thick glass coverslips with an adjustable gap between them, a second layer of refractive index matching oil with a refractive index of 1.5120, and a metal plate connected to a translation stage to produce a change in the distance between the first and second glass coverslips. The distance between the two coverslips is varied by rotating a microscrew with a resolution of 25 μm per rotation. The SS-OCT signal is generated by the interference between light reflected from the first glass-air interface and the second glass-gas interface.

[0304] (Example 2) Performance of a VCSEL driven outside its rated operating range Figure 15 shows the oscilloscope signals of a VCSEL driven outside its rated operating range at two different points in time. The VCSEL had a rated range of a center wavelength of approximately 850 nm and an emission wavelength of approximately 1.8 nm. The VCSEL current was continuously swept in a triangular pattern with a maximum current of 15 mA. The current was swept at a frequency of 125 Hz. The experiment consisted of four intervals of continuous sweeps, each lasting approximately 7.25 hours. Between each interval, the VCSEL was deactivated for several hours. The VCSEL current (green), VCSEL power (red), and interference signal (purple) were recorded at least every two hours. The measurements of all three parameters showed little variation between the first measurement at 0 hours of operation and subsequent measurements after the VCSEL had been operating for 29 hours. Therefore, it can be concluded that a VCSEL driven outside its rated operating range can continue to produce useful SS-OCT measurements after at least 29 hours of use. This is in line with the requirements and advantages of using a VCSEL implemented in a handheld SS-OCT device. Assuming the device is used twice a day for 20 seconds per measurement over a five-year period, the VCSEL would accumulate approximately 20 hours of active use. Therefore, a handheld SS-OCT device based on a VCSEL driven outside its rated operating range may continue to produce useful results throughout its entire intended operating life.

[0305] (Example 3) OCT signal for fluctuating thickness Figure 16 shows oscilloscope signals for two different configurations of the optical setup in Figure 14. The VCSEL had a center wavelength of approximately 850 nm and a rated emission wavelength range of approximately 1.8 nm. The VCSEL current was continuously swept in a triangular pattern with a maximum current of 15 mA. The current was swept at a frequency of 125 Hz. The VCSEL drive current (green) and interference signal (purple) were recorded using an oscilloscope. Two glass cover slides, 150 μm thick, were placed at an arbitrary distance apart, referred to as the zero position. The zero position was selected so that 2-3 periods were recorded from the interference signal resulting from light reflected from the first and second glass cover slides. Changes in the distance between the two glass cover slides resulted in changes in the frequency of the vibration of the interference signal. For example, at the zero position, the interference signal fluctuated with a frequency of approximately 950 Hz. After adding a 25.0 μm displacement from the zero position to the distance between the two coverslips, the interference signal varied with a frequency of approximately 1,050 Hz.

[0306] (Example 4) Frequency extraction from interference signals Figure 17 illustrates a signal processing method for extracting the oscillation frequencies of an interference signal generated using an SS-OCT system that utilizes a single VCSEL and does not employ a reference arm. The interference signal recorded on the oscilloscope is corrected by dividing the interference signal by the VCSEL light intensity. This generates a slowly decaying sine wave. The corrected data is then fitted to the sine wave using a nonlinear least-squares fitting means. The oscillation frequencies of the corrected interference signal are extracted from the nonlinear least-squares fitting.

[0307] (Example 5) Repeatability measurement Figure 18 shows the results of a study to determine the repeatability of extracting the frequency of vibrations of an interference signal generated using an SS-OCT system that utilizes a single VCSEL and does not use a reference arm. The distance between the two glass coverslips was varied in increments of 12.5 μm. The sinusoidal fitted frequency was obtained from the interference signal at each value of the distance between the two glass coverslips. The experiment was replicated 5 to 10 times for each value of the distance between the two glass coverslips.

[0308] Figure 19 shows the mean and 95% confidence interval of frequencies acquired during a study to determine the reproducibility of extracting the frequencies of vibrations of interference signals generated using an SS-OCT system that utilizes a single VCSEL and does not utilize a reference arm. Excluding the 25 μm and 37.5 μm data points, each inspected distance is separated from other inspected distances by more than two standard deviations from distances 12.5 μm below and 12.5 μm above it. For all data points, each inspected distance is separated from other inspected distances by more than two standard deviations from distances 25.0 μm below and 25.0 μm above it. Thus, it can be inferred that this method for determining changes in layer thickness (here, the gap between two glass coverslips) has a limit in detecting changes in layer thickness between 12.5 μm and 25.0 μm. This is favorably comparable to the operating requirements of a handheld SS-OCT system for measuring changes in RT.

[0309] (Example 6) Fundus imaging Figures 37A–C show exemplary fundus images acquired using the systems and methods described herein. Figure 37A shows a fundus image with relatively high contrast and a relatively high amount of observable structure. Figure 37B shows a fundus image with relatively low contrast and a relatively low amount of observable structure. Figure 37C shows a corrected fundus image that has undergone the fundus recognition method described herein. The fundus image in Figure 37C was acquired by applying the fundus recognition method described herein to the image in Figure 37B (a fundus image with relatively low contrast and a relatively low amount of observable structure). As shown in Figure 37C, the veins of the fundus are clearly identified using the fundus recognition method described herein. Thus, the fundus recognition method is capable of detecting substructures of the fundus within a fundus image even when the fundus image is of relatively low quality. Substructures of the fundus can be used for image registration.

[0310] (Example 7) Chirp correction resampling Figures 38A and 38B show the effect of resampling for chirp correction of SS-OCT signals in the time domain. Figure 38A shows the effect of resampling for chirp correction of SS-OCT signals with relatively low frequencies. Figure 38B shows the effect of resampling for chirp correction of SS-OCT signals with relatively high frequencies. The results of the resampling procedure are shown in the frequency domain of Figures 39A and 39C.

[0311] (Example 8) Frequency drift of uncorrected and chirp-corrected SS-OCT signals Figures 39A-C show the frequency drift of uncorrected and chirp-corrected SS-OCT signals in the frequency domain. Figure 39A shows the frequency drift of an SS-OCT signal that has not been corrected by the resampling method for chirp correction described herein. The uncorrected SS-OCT signal exhibits a drift of over 50 kHz over a period of approximately 2 seconds. Figure 39B shows the frequency drift of an SS-OCT signal that has been pre-sampled for chirp correction. The signal exhibits a significantly smaller frequency drift, fluctuating by only a few Hz over a period of approximately 2 seconds. Figure 39C shows the frequency drift of an SS-OCT signal that has undergone final resampling for chirp correction. The signal exhibits an even smaller frequency drift, fluctuating by only a small amount over a period of approximately 1.6 seconds. Thus, the frequency drift can be corrected using chirp correction or resampling methods as described herein. Reducing frequency drift using the resampling methods described herein results in a narrower measured frequency distribution, leading to more precise RT or RLT measurements with a higher signal-to-noise ratio.

[0312] (Example 9) Phase drift caused by various noise sources Figures 40A-C show exemplary phase drift of an uncorrected SS-OCT signal associated with various noise sources. Figure 40A shows the phase drift of an uncorrected SS-OCT signal associated with noise caused by vibration. The large sharp rise in the bandwidth of the SS-OCT signal is due to intentionally hitting the floor. Figure 40B shows the phase drift of an SS-OCT signal associated with noise caused by fluctuating spatial filtering of the light source. The bandwidth of the SS-OCT signal fluctuates by up to 2 kHz over time. Figure 40C shows the phase drift of an SS-OCT signal associated with noise levels caused by optimal conditions. After transient behavior, the SS-OCT signal settles to a relatively constant bandwidth when operating conditions are kept as constant as possible. Even in this ideal situation, the bandwidth of the SS-OCT signal still fluctuates by up to 500 Hz over time. Thus, it can be seen that an uncorrected SS-OCT signal can experience significant changes in bandwidth even when operating under ideal conditions. The SS-OCT signal can be corrected using a resampling method, as described herein, to significantly reduce bandwidth variations over time.

[0313] (Example 10) Correction of phase shift associated with patient movement Figures 41A–D show simulations of phase shift associated with patient movement. Figure 41A shows the simulated signal with a π-radian phase shift over a duration of half the signal length. Figure 41A shows the frequency spectrum of the simulated signal with a π-radian phase shift over a duration of half the signal length. A π-radian phase shift corresponds to approximately 225 nm of patient movement with respect to light having a wavelength of 850 nm. The phase shift introduces a significant error in the frequency spectrum. Figure 41C shows the simulated signal with a π-radian phase shift over the duration of a single cycle of the signal. Figure 41D shows the frequency spectrum of the simulated signal with a π-radian phase shift over the duration of a single cycle of the signal. Although present only for short time periods, the phase shift still introduces a significant error in the frequency spectrum. These phase shifts can be corrected by utilizing fast A-scanning or chirp correction methods, as described herein.

[0314] Figures 42A–D illustrate the simulation of the effect of A scan duration on errors arising from phase shift associated with patient movement. Figure 42A shows a simulated signal with a phase shift of π radians over the duration of a single cycle of the signal with an A scan duration of 2 milliseconds. Figure 42B shows the frequency spectrum of the simulated signal with a phase shift of π radians over the duration of a single cycle of the signal with an A scan duration of 2 milliseconds. The phase shift imparts a significant error to the frequency spectrum over this relatively long A scan duration. Figure 42C shows a simulated signal with a phase shift of π radians over the duration of a single cycle of the signal with an A scan duration of 0.4 milliseconds. Figure 42D shows the frequency spectrum of the simulated signal with a phase shift of π radians over the duration of a single cycle of the signal with an A scan duration of 0.4 milliseconds. The phase shift imparts a significantly smaller error to the frequency spectrum over this relatively short A scan duration. Thus, noise associated with patient movement can be reduced by utilizing fast A scans as described herein.

[0315] (Example 11) Measurement of typical patient movement Figures 43A-B show the amplitude of typical patient movement. Figure 43A shows movement along the optical axis of a patient who is as stationary and fixed as possible. Large jumps between positions are caused by the patient blinking. Neglecting blinking, typical patient movement has an amplitude of approximately 0.25 mm and a duration of approximately 1.2 seconds, with respect to a typical movement speed of 210 nm / millisecond. Such movement speeds can be corrected by using the high-speed A scanning described herein. Maximum patient movement has an amplitude of approximately 0.25 mm and a duration of approximately 0.16 seconds, with respect to a maximum movement speed of 1,560 nm / millisecond. Figure 43B shows movement along the optical axis of a patient who is intentionally moving. Neglecting blinking, typical intentional patient movement has an amplitude of approximately 2.19 mm and a duration of approximately 0.76 seconds, with respect to a typical movement speed of 2,900 nm / millisecond.

[0316] Preferred embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. The present invention is not intended to be limited by the specific examples provided herein. While the present invention is described with reference to the preceding specification, the descriptions and illustrations of embodiments herein are not intended to be constrained. Numerous variations, modifications, and substitutions will be recalled herein by those skilled in the art without departing from the present invention. Furthermore, it should be understood that all aspects of the present invention are not limited to the specific descriptions, configurations, or relative proportions described herein, depending on various conditions and variables. It should be understood that various alternatives to the embodiments of the present invention described herein may be employed in practicing the present invention. Therefore, it is considered that the present invention should also cover any such alternatives, modifications, variations, or equivalents. The following claims define the scope of the present invention, and methods and structures within the scope of these claims and their equivalents are intended to be covered thereby.

Claims

1. An optical coherence tomography (OCT) system for measuring the thickness of an object, wherein the OCT system is Detector and A light source comprising a vertical cavity surface-emitting laser (VCSEL), wherein the VCSEL is configured to generate a light beam using a drive current to the VCSEL, the light beam comprises multiple wavelengths, the VCSEL is configured to scan across a range of wavelengths by varying the drive current, and the VCSEL has a maximum rated current for continuous use. A plurality of optical elements coupled to the light source, wherein the plurality of optical elements direct the light beam into the eye and generate an interference signal in the detector, The detector and the circuit coupled to the light source Equipped with, The circuit determines the thickness in response to the interference signal. The circuit is configured to extend the wavelength range using the drive current to the VCSEL by driving the VCSEL beyond the maximum rated current for continuous use. The OCT system is configured to be held in the patient's hand.

2. The OCT system according to claim 1, wherein the thickness includes the distance between the first layer of the object and the second layer of the object, and the thickness is greater than 150 μm.

3. The OCT system according to claim 1, wherein the light source, the plurality of optical elements, the detector, and the circuit are configured to be held in front of the eye with the detector at a distance of 200 mm or less from the eye.

4. The OCT system according to claim 1, further comprising a visual target for aligning the light beam with the orbit, wherein the visual target comprises one or more of the light beam or light from a light-emitting diode.

5. The OCT system according to claim 1, wherein the VCSEL has a specified wavelength range of wavelength variation corresponding to the maximum rated current for continuous use, and the circuit is configured to drive the VCSEL beyond the specified wavelength range of wavelength variation by exceeding the specified wavelength range of wavelength variation by a range of 1 nm to 5 nm.

6. The OCT system according to claim 1, wherein the VCSEL has a specified wavelength range of wavelength variation corresponding to the maximum rated current for continuous use, the circuit is configured to drive the VCSEL above the specified wavelength range of wavelength variation for each of a plurality of measurements, and to delay the second measurement from the first measurement by an amount in the range of 1 millisecond ("ms") to 100 milliseconds in order to prevent overheating of the VCSEL.

7. The OCT system according to claim 1, wherein the circuit is configured to drive the VCSEL with a waveform exceeding the maximum rated current for continuous use, the waveform having a first portion exceeding the maximum rated current of the VCSEL and a second portion below the maximum rated current of the VCSEL.

8. The OCT system according to claim 1, wherein the circuit is configured to sweep over a range of wavelengths to the radiation wavelength with a sweep frequency, and the circuit is configured to determine the thickness in response to the frequency of the interference signal.

9. The OCT system according to claim 1, wherein the plurality of optical elements are arranged to provide a reference optical path and a measurement optical path, and the interference signal is due to the interference of light along the reference optical path and the measurement optical path.

10. The OCT system according to claim 1, wherein the circuit comprises a processor configured to convert the interference signal into an intensity profile of light reflected along the optical path of the light beam directed into the eye, and to determine the thickness of the retina in response to the intensity profile.

11. The OCT system according to claim 1, further comprising a visual target for aligning the OCT system with the orbit, wherein the visual target comprises one or more of the light beam, a target defined using a light-emitting diode, or a VCSEL.

12. The OCT system according to claim 1, wherein the light source comprises a first VCSEL and a second VCSEL, and the light beam comprises light from the first VCSEL and the second VCSEL.

13. The OCT system according to claim 12, wherein the circuit is configured to drive the first VCSEL and the second VCSEL sequentially using similar sweep frequencies to sweep the first wavelength of light from the first VCSEL and the second wavelength of light from the second VCSEL at similar speeds.

14. The OCT system according to claim 12, wherein the circuit is configured to turn on the first VCSEL when the second VCSEL is off, and to turn on the second VCSEL when the first VCSEL is off, thereby preventing temporal overlap of light from the first VCSEL and the second VCSEL, and the second VCSEL is configured to turn on when the first VCSEL is turned off and emit light having a wavelength of 0.1 nm or less of the light from the first VCSEL.

15. The OCT system according to claim 1, further comprising a housing for supporting the light source, the optical element, the detector, and the circuit, wherein the housing is configured to be held in the hand of a user in front of the eye to direct the light beam into the eye.

16. The OCT system according to claim 15, further comprising a battery, wherein the battery is located further away from the detector than the light source.

17. The OCT system according to claim 16, further comprising a docking station, the docking station receiving the housing and charging the battery contained within the housing in order to supply power to the light source and the circuit, and the docking station comprising a wireless communication circuit for transmitting the thickness to a remote server.

18. The OCT system according to claim 17, wherein the wireless communication circuit comprises a Global Systems for Mobile Communications (GSM), third-generation (3G), or fourth-generation (4G) module.

19. The OCT system according to claim 1, wherein the circuit is configured to receive or transmit data through a communication network.

20. The OCT system according to claim 19, wherein the communication network includes the Internet, a cellular network, or a short-range communication network.

21. The OCT system according to claim 1, further comprising a mirror, a plurality of mirrors, a gimbal, a lens, a galvanometer, an acousto-optic modulator, an electro-optic modulator, a translation optical element, an optical element that translates across the light beam, a deformable mirror, and a scanning optical element selected from the group consisting of xy translation stages.

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