Optical coherence tomography system to measure thickness of retina

Abstract

To provide optical coherence tomography (OCT) systems and methods.SOLUTION: Improved optical coherence tomography systems and methods to measure thickness of the retina are presented. The systems may be compact, handheld, provide in-home monitoring, allow a patient to measure himself or herself, and be robust enough to be dropped while still measuring the retina reliably. In one embodiment, the compact OCT system measures a change in retinal thickness at a precision (or repeatability) less than an axial resolution of the compact OCT system, change in retinal thickness includes a first thickness at a first time and a second thickness at a second time.SELECTED DRAWING: None

Description

[Technical field]

[0001] (cross reference) This application is a continuation of U.S. Provisional Patent Application No. 62 / 437,486, filed December 21, 2016, entitled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications," U.S. Provisional Patent Application No. 62 / 539,382, filed July 31, 2017, entitled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications," U.S. Provisional Patent Application No. 62 / 546,935, filed August 17, 2017, entitled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications," and U.S. Provisional Patent Application No. 62 / 547,314, filed August 18, 2017, entitled "Miniaturized Mobile, Low Cost Optical Coherence Tomography System for Home Based Ophthalmic Applications." No. 6,399,345, filed on Oct. 23, 2003, and claims priority to "Patent Application No. 6,399,345," which is incorporated by reference herein in its entirety for all purposes. [Background technology]

[0002] The eye is important for vision; 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 on it, 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, providing sharp and clear vision. Unfortunately, diseases of the retina can adversely 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 an increase in retinal thickness and take or are treated with medications. Macular edema is an example of an increase in retinal thickness, often associated with other diseases such as diabetes. Macular edema can be associated with other diseases such as age-related macular degeneration, uveitis, blockage of the retinal vasculature, and glaucoma. It would be helpful to quickly know if a drug is not working or needs re-administration 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 previous OCT systems are overly complex and expensive and are not suitable for monitoring retinal thickness on a regular basis, such as weekly or daily. Previous standards of eye care involve 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 previous OCT systems are not suitable for home monitoring or mobile healthcare. Such previous systems are typically heavier than an individual can easily carry and are not suitable for traveling with the patient. In addition, previous OCT systems are more complex than would be ideal and are not suitable for daily use and hazards such as dropping. Previous costs of OCT systems may be beyond what a typical patient can afford. Furthermore, use of previous OCT systems may require trained operators. For the above reasons, home monitoring of retinal thickness has not been adopted because previous standards of care and previous care of patients with retinal disease may be less than ideal in many cases.

[0005] In light of the above, it would be useful to have improved OCT systems and methods for measuring retinal thickness. Ideally, such a system would be small, handheld, provide in-home monitoring, allow patients to measure themselves, and be rugged enough to withstand a drop while still reliably measuring the retina. Summary of the Invention [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. Although specific reference is made to measuring retinal thickness, the compact OCT systems and methods disclosed herein will find application in many fields, such as microscopy, metrology, aerospace, astronomy, telecommunications, medicine, pharmaceuticals, dermatology, dentistry, and cardiology.

[0007] The compact OCT system includes multiple components arranged to provide a reduced optical path and weight. In many embodiments, the compact OCT system is configured to measure thickness changes in the retina that are less than the resolution value of the OCT system, which allows the size, cost, and complexity to be significantly reduced. The system is repeatable and reproducible enough to accurately detect thickness changes in the retina that are less than the system axial resolution value. The compact OCT system is capable of scanning a wavelength range and acquiring OCT data at a sufficient speed to reduce errors associated with the movement of the system with respect to the eye. In many embodiments, the compact OCT system is calibrated to a specific patient using a clinical reference system that has a higher resolution than the compact OCT system, and the compact OCT system is calibrated to a specific patient based on the retinal thickness measured using the clinical reference system. In some cases, the compact OCT system includes a calibration kit or device that allows the system to be tested to ensure that the repeatability and reproducibility remain within acceptable tolerances.

[0008] In some cases, the miniature OCT system is configured to be held in a 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 the miniature spectrometer while the patient holds the measurement component of the system in their hand. The miniature OCT system includes a housing for containing the measurement component, the housing being dimensioned such that, in some cases, a user can easily grasp the housing, lift the measurement component within the housing, and align the OCT system with their eye. The compactness and reduced mass of the OCT system allows the system to be easily held in a patient's hand and transported with the patient. In many embodiments, the tomography system includes a maximum dimension across within a range of about 80 mm to about 160 mm and a mass within a range of about 100 grams to about 500 grams. In many embodiments, the OCT system is configured with no internal moving parts to increase the reliability of the system. The miniature OCT system is optionally configured to be dropped from a distance of about one foot and provide measurement repeatability and accuracy of, for example, retinal thickness of about 25 μm or less.

[0009] In some embodiments, the compact OCT system includes a light source configured to emit a plurality of wavelengths, a detector, an optical element arranged to generate an optical interference signal on the detector, and a circuit coupled to the detector and the light source. In some embodiments, the light source includes a light source configured to emit a light beam of varying wavelengths to sweep the wavelength over a range of wavelengths. In some cases, the wavelength is swept over a range of about 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 the OCT system within the range of 3 nm to 10 nm allows, for example, detection of retinal thicknesses greater than about 150 μm and thickness changes in retina as small as 25 μm with the compact OCT system, although longer wavelength sweeps can be used. The circuit is configured to drive the light source with a waveform having a characteristic period and sweep frequency, such as a sawtooth waveform, in some embodiments. In one instance, the circuit is coupled to a detector to measure the frequency of an interference signal from light returning from the eye and determine the thickness of the retina of the eye, although thicknesses of other objects can also be measured. In some embodiments, the circuit is configured to drive the light source above a maximum rated current threshold for one portion of the waveform and below a maximum rated current threshold for another portion of the waveform, such that the light source emits light during both portions of the waveform. This overdriving of the light source within one portion of the waveform allows for an expansion of the wavelength range of the light source and an increase in the 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) 1. A compact optical coherence tomography (OCT) system for measuring retinal thickness, the compact OCT system comprising: A detector; a light source configured to generate a light beam having a plurality of wavelengths; a plurality of optical elements coupled to the light source, the plurality of optical elements directing the beam into the eye and generating an interference signal at the detector; a circuit coupled to the detector and the light source; Equipped with The circuitry responds to the signal to determine a thickness of the retina. 2. The compact OCT system of item 1, wherein 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, the thickness changes in the retina comprising a first thickness at a first time and a second thickness at a second time. (Item 3) 2. The compact OCT system of item 1, wherein the thickness change in the retina measured using the compact OCT system is less than the axial resolution of the compact OCT system. (Item 4) 3. The compact OCT system of claim 2, wherein the axial resolution has a resolution value in the range of about 150 μm to about 30 μm, and optionally, the value is in the range of about 150 μm to about 75 μm. (Item 5) 2. The compact OCT system of claim 1, wherein the light beam has a variable wavelength and the circuitry is configured to vary the wavelength using a drive current from the circuitry. (Item 6) 2. The compact OCT system of item 1, wherein the retinal thickness comprises a distance between a first layer of the retina and a second layer of the retina, and the retinal thickness is greater than 150 μm. (Item 7) 2. The compact OCT system of item 1, wherein the retinal thickness is in the range of about 150 to 300 μm, the wavelength range is swept in the range of about 2 nm to about 10 nm, and the OCT system has an axial resolution in the range of about 150 μm to about 30 μm, optionally, the wavelength range is swept from about 3 nm to about 6 nm, the axial resolution is in the range of about 100 μm to about 50 μm, and optionally, the light source comprises a single VSCEL. (Item 8) 8. The compact OCT system of item 7, wherein the repeatability between successive 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 a test subject. (Item 9) 9. The compact OCT system of item 8, wherein the compact OCT system is configured to determine a change in the thickness when two measurements of the thickness produce two thickness values ​​that differ by more than 50 μm. (Item 10) 9. The compact OCT system of item 8, wherein the repeatability is based on measurements performed within 1 minute and determined with a 95% confidence interval. (Item 11) 9. The compact OCT system of item 8, wherein the reproducibility is within 25 μm, the reproducibility representing the variation in measurements made by one individual on the retina within a predetermined period of time under a set of conditions. (Item 12) 12. The compact OCT system of item 11, wherein the predetermined period is at least two months. (Item 13) Item 12. The compact OCT system of item 11, further comprising an inspection device that provides an inspection material having a plurality of reflective surfaces. (Item 14) 2. The miniature OCT system of item 1, wherein the thickness is measured faster than a characteristic frequency of movement of the miniature OCT system relative to the eye, the movement being selected from the group consisting of movement associated with a patient holding the OCT system in their hand, eye movement, and tremor. (Item 15) 15. The compact OCT system of item 14, wherein the compact OCT system is configured to perform measurements at frequencies within a 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) 2. The compact OCT system of item 1, wherein the light source, the plurality of optical elements, the detector, and the circuitry are configured to be held in front of the eye with the detector no more than about 200 mm from the eye. (Item 17) 2. The compact OCT system of claim 1, further comprising a visual target for the patient to align the light beam with the orbit, the visual target comprising one or more of the light beam or light from a light emitting diode. (Item 18) 2. The compact OCT system of item 1, wherein the light source comprises a vertical cavity surface emitting laser (VCSEL) configured to vary the emission wavelength of the light beam over a range of approximately 5 to 10 nm. (Item 19) 20. The compact OCT system of claim 18, wherein the VCSEL has a specified maximum rated range of wavelength variation. (Item 20) 20. The compact OCT system of claim 19, wherein the circuitry is configured to drive the VCSEL at least about 1 nm beyond the specified maximum range of wavelength variation, optionally within about 1 nm to 5 nm beyond the specified maximum range of wavelength variation. (Item 21) 22. The compact OCT system of claim 19, wherein the circuitry is configured to drive the VSCEL above a maximum of a rated wavelength range for each of a plurality of measurements and to delay a first measurement from a second measurement by an amount in a range of about 1 millisecond ("ms") to about 100 milliseconds, optionally in a range of about 5 milliseconds to about 20 milliseconds, to prevent overheating of the VSCEL. 20. The compact OCT system of claim 19, wherein the circuit is configured to drive the VSCEL above a maximum of the rated wavelength range with a drive current having a waveform having a first portion above a maximum rated current of the VSCEL and a second portion below the maximum rated current of the VSCEL, the first portion having less than about 50 percent of the duration of the waveform to prevent overheating of the VSCEL. (Item 23) 2. The compact OCT system of item 1, wherein the circuitry is configured to cause the emission wavelength to sweep over a range of wavelengths with a sweeping frequency, and the circuitry is configured to determine the thickness in response to a frequency of the interference signal. (Item 24) 24. The compact OCT system according to item 23, wherein the sweep frequency is in the range of about 50 Hz to about 10 KHz, optionally in the range of about 100 Hz to about 5 kHz or about 1 kHz to about 5 KHz. (Item 25) 24. The compact OCT system of claim 23, wherein the sweep frequency is faster than a tremor of a user's eye or a tremor of the user's hand. (Item 26) 2. The compact OCT system of item 1, wherein the circuit is configured to heat the light source to change the wavelength. (Item 27) 2. The compact OCT system of item 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 interference of light along the reference optical path and the measurement optical path. (Item 28) 2. The compact OCT system of item 1, wherein the plurality of optical elements are arranged to provide a reference optical path and a measurement optical path, and the interference signal results from interference of light from the reference optical path and light from the measurement optical path. (Item 29) 2. The compact OCT system of item 1, wherein the plurality of optical elements are arranged to provide a measurement optical path, and the interference signal is due to interference of light from a layer of the retina along the measurement optical path, optionally without a reference optical path. (Item 30) 2. The compact OCT system of claim 1, wherein the circuitry includes a processor configured to convert the interference signal into an intensity profile of light reflected along an optical path of the beam directed into the eye and to determine a thickness of the retina in response to the intensity profile. (Item 31) 31. The compact OCT system of claim 30, wherein the intensity profile comprises a plurality of reflection peaks, and the processor is configured with instructions for determining the thickness in response to the plurality of reflection peaks. (Item 32) 31. The compact OCT system of item 30, wherein the processor is configured with instructions for determining the intensity profile in response to a 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) 31. The compact OCT system of claim 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) 31. The compact OCT system of claim 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) Item 1, the compact OCT system further comprising a viewing target for aligning the tomography system with an eye socket, the viewing target comprising one or more of the light beam, a target defined using a light emitting diode, or a VCSEL. (Item 36) 2. The compact OCT system of 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. (Item 37) Item 37. The compact OCT system of item 36, wherein the circuitry is configured to drive the first VCSEL and the second VCSEL in sequence with 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 a similar rate, optionally the similar sweep frequencies and the similar rates of the first VSCEL and the second VSCEL are within 5% of each other, optionally within 1% of each other. (Item 38) Item 37. The compact OCT system of 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 to prevent 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 about 0.1 nm of the light from the first VSCEL. (Item 39) Item 37. The compact OCT system of item 36, further comprising one or more of a beam splitter or an optical fiber for coupling light from the first VSCEL. (Item 40) 2. The compact OCT system of claim 1, further comprising a housing for supporting the light source, the optical elements, the detector, and the circuitry, the housing being configured to be held in a user's hand in front of the eye to direct the light beam into the eye. (Item 41) Item 41. The compact OCT system of item 40, wherein the housing has a cylindrical shape with multiple indentations on a curved surface to facilitate gripping. (Item 42) 41. The compact OCT system of item 40, further comprising a sensor for measuring the eye measured in response to an orientation of the housing. (Item 43) Item 41. The compact OCT system of item 40, further comprising an occlusion structure for occluding one eye while the other eye is being measured, the occlusion structure being coupled to the housing and the sensor for determining the eye being measured. (Item 44) 41. The compact OCT system of item 40, wherein the housing comprises a body and a lid rotatably attached to the body, the lid being configured to rotate around the body when in an open position. (Item 45) Item 41. The compact OCT system of item 40, further comprising a battery, the battery being located farther from the detector than the light source. (Item 46) 46. ​​The compact OCT system of item 45, further comprising a docking station that receives the housing and charges the battery contained within the housing to power the light source and the circuitry, the docking station comprising wireless communication circuitry for transmitting the thickness to a remote server, and optionally, the wireless communication circuitry comprising a Global System for Mobile Communications (GSM), third generation (3G), or fourth generation (4G) module. (Item 47) 2. The compact OCT system of item 1, wherein the circuitry is configured to receive or transmit data over a communications network. (Item 48) 2. The compact OCT system of item 1, wherein the communication network includes the Internet, a cellular network, or a short-range communication network. (Item 49) 49. The compact OCT system of any one of items 1 to 48, wherein the compact OCT system has a mass in the range of about 50 grams to about 500 grams, optionally in the range of about 100 grams to about 400 grams. (Item 50) 50. The compact OCT system of any one of items 1 to 49, wherein the compact OCT system has a maximum distance traversed within a range of about 10 mm to about 100 mm, optionally within a range of about 25 mm to about 70 mm. (Item 51) a housing, the light source, the detector, the circuitry, and the optical elements being contained within the housing; and an optical fiber coupled to the light source and the detector, the optical fiber extending from the miniature OCT system; an alignment structure coupled to a distal end of the optical fiber to align the light beam with the eye and direct the light beam toward the eye; 51. The compact OCT system according to any one of items 1 to 50, further comprising: (Item 52) 1. A method for measuring a retinal thickness in a patient using a miniature OCT system, the method comprising: repeatedly measuring said retinal thickness, thereby performing a plurality of measurements at a plurality of times respectively; detecting a change in thickness within a range of about 30 μm to about 70 μm based on the plurality of measurements. Including, The method, wherein the miniature OCT system has an axial resolution in the range of about 70 μm to about 150 μm. (Item 53) Item 53. The method of item 52, wherein the thickness is measured using a wavelength sweep in the range of about 5 nm to 10 nm. (Item 54) 53. The method of claim 52, wherein the repeated measurements include performing a first measurement based on a second OCT system having a lower resolution value than the compact OCT system within 24 hours of a visit to an ophthalmologist, adjusting the thickness measured using the compact OCT system, and performing a second measurement at a time within a range of 1 to 20 days after the first measurement. (Item 55) 53. The method of claim 52, wherein the repeated measurements include performing one measurement daily over a number of days within a range of about 5 to 20 days. (Item 56) 53. The method of claim 52, wherein the multiple times are separated from one another by at least 1 day and not more than 20 days. (Item 57) 53. The method of claim 52, wherein the change in thickness is detected with at least a 95% confidence interval. (Item 58) 1. A compact OCT system for measuring a thickness of an object, the compact OCT system comprising: A detector; a light source configured to generate a light beam having a tunable wavelength; a plurality of optical elements coupled to the light source to direct the beam into the object and generate an interference signal on a detector; a circuit coupled to the detector and the light source; Equipped with The circuit varies the wavelength and responds to the interference signal to determine the thickness. (Item 59) 59. The compact OCT system or method of any one of claims 1 to 58, further comprising a scanning optical element selected from the group consisting of 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. (Item 60) 60. The miniature OCT system or method of any one of items 1 to 59, further comprising a visual camera device. (Item 61) Item 61. The compact OCT system or method of item 60, wherein the visual camera device is configured to acquire multiple images of the subject's eye. (Item 62) Item 62. The compact OCT system or method of item 61, wherein the multiple images of the subject's eye are used to determine whether and the amount of movement of the subject's eye between subsequent OCT measurements. (Item 63) 63. The miniature OCT system or method according to any one of items 1 to 62, further comprising a fundus camera device. (Item 64) Item 64. The compact OCT system or method of item 63, wherein the fundus camera is configured to acquire multiple images of the fundus of the subject's eye. (Item 65) Item 65. The compact OCT system or method of item 64, wherein the multiple images of the fundus of the subject's eye are used to determine whether and the amount by which the subject's eye has moved between subsequent OCT measurements.

[0010] (Cited by reference) All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0011] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

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

[0013] [Diagram 2] FIG. 2 shows a schematic diagram of a system that allows a patient to measure retinal thickness (RT) at multiple time points and communicate the results, according to some embodiments.

[0014] [Figure 3A] FIG. 3A illustrates a handheld optical coherence tomography (OCT) device that utilizes Bluetooth® communication, according to some embodiments.

[0015] [Figure 3B] FIG. 3B illustrates a handheld OCT device that utilizes Global System for Mobile Communications (GSM), according to some embodiments.

[0016] [Figure 4] FIG. 4 shows a schematic diagram of the flow of information within a handheld OCT system, according to some embodiments.

[0017] [Diagram 5] FIG. 5 shows a schematic diagram of a swept-source optical coherence tomography (SS-OCT) device, according to some embodiments.

[0018] [Figure 6A] FIG. 6A shows a schematic diagram of an SS-OCT device lacking a reference mirror, according to some embodiments.

[0019] [Figure 6B] FIG. 6B illustrates the wavelength range over which a vertical cavity surface emitting laser (VCSEL) operates in an SS-OCT device lacking a reference mirror, according to some embodiments.

[0020] [Figure 7A] FIG. 7A shows a schematic diagram of a SS-OCT device utilizing an external cavity, according to some embodiments.

[0021] [Figure 7B] FIG. 7B illustrates the wavelength range over which a VCSEL operates in an SS-OCT device lacking a reference mirror, according to some embodiments.

[0022] [Figure 7C] FIG. 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] FIG. 8A shows a schematic diagram of an SS-OCT device utilizing two VCSELs and lacking a reference mirror at a first particular point in time, according to some embodiments.

[0024] [Figure 8B] FIG. 8B shows a schematic diagram of an SS-OCT device utilizing two VCSELs and lacking a reference mirror at a second particular point in time in accordance with some embodiments.

[0025] [Figure 8C]FIG. 8C illustrates the wavelength range over which a VCSEL operates in an SS-OCT device utilizing two VCSELs and lacking a reference mirror, according to some embodiments.

[0026] [Figure 9] FIG. 9 illustrates operation of a VCSEL beyond its maximum current rating, according to some embodiments.

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

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

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

[0030] [Figure 10D] FIG. 10D shows a graphical representation of the repeatability and reproducibility associated with measuring RT in retinas that exhibited changes in RT.

[0031] [Figure 11] FIG. 11 is a flow chart of a method for taking repeated measurements of a patient's RT over time and noting changes that may correspond to adverse outcomes.

[0032] [Figure 12] FIG. 12 shows a flow chart of a method for determining RT from measurements using a handheld OCT device.

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

[0034] [Figure 14]FIG. 14 shows the optical setup for determining the limit of detection of a SS-OCT system utilizing a single VCSEL and no reference arm.

[0035] [Figure 15] FIG. 15 shows the oscilloscope signal at two different times of a VCSEL driven outside its rated operating range.

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

[0037] [Figure 17] FIG. 17 illustrates a signal processing method for extracting the frequency of oscillation of an interference signal generated using an SS-OCT system utilizing a single VCSEL and no reference arm.

[0038] [Figure 18] FIG. 18 shows the results of a study to determine the repeatability of extracting the frequency of oscillation of an interference signal generated using an SS-OCT system utilizing a single VCSEL and no reference arm.

[0039] [Figure 19] FIG. 19 shows the average and 95% confidence intervals of the frequencies obtained during a study to determine the repeatability of extracting the frequency of oscillation of an interference signal generated using an SS-OCT system utilizing a single VCSEL and no reference arm.

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

[0041] [Figure 20B] FIG. 20B shows a handheld OCT system adapted to measure either the right or left eye.

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

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

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

[0045] [Figure 22] FIG. 22 shows a schematic diagram of an SS-OCT device utilizing a scanning mechanism, according to some embodiments.

[0046] [Figure 23A] FIG. 23A shows a schematic diagram of a scanning mechanism, according to some embodiments.

[0047] [Figure 23B] FIG. 23B shows an array of retinal layer thickness measurement sites, according to some embodiments.

[0048] [Figure 24] FIG. 24 shows a schematic diagram of an SS-OCT device utilizing a scanning mechanism and one or more cameras, according to some embodiments.

[0049] [Diagram 25] FIG. 25 illustrates a method for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to some embodiments.

[0050] [Figure 26] FIG. 26 shows a schematic diagram of an SS-OCT device incorporating a visual function measuring apparatus, according to some embodiments.

[0051] [Figure 27]27A and 27B show visual cues on a background according to some embodiments.

[0052] [Figure 28] 28A and 28B show configurations of a handheld monocular OCT system according to some embodiments.

[0053] [Figure 29] 29A, 29B, and 29C show an exemplary handheld binocular OCT system configuration, according to some embodiments.

[0054] [Diagram 30] FIG. 30 illustrates an exemplary handheld binocular OCT system configuration, according to some embodiments.

[0055] [Figure 31A] FIG. 31A shows a handheld binocular OCT system oriented to measure a subject's left eye, according to some embodiments.

[0056] [Figure 31B] FIG. 31B shows a housing for a handheld binocular OCT system oriented to measure the right eye of a subject, according to some embodiments.

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

[0058] [Figure 32B] FIG. 32B shows a schematic diagram of a VCSEL coupled to a thermoelectric cooler, according to some embodiments.

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

[0060] [Figure 33B] FIG. 33B shows a user using a miniature SS-OCT device mounted on a support, according to some embodiments.

[0061] [Diagram 34] FIG. 34 shows a schematic diagram of the optical system of a SS-OCT device incorporating a fixation targeting device and a fundus imaging device, according to some embodiments.

[0062] [Diagram 35] FIG. 35 shows a schematic diagram of an electronic circuit board for controlling the optics of the compact SS-OCT system described herein, according to some embodiments.

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

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

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

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

[0067] [Figure 40A] 40A, 40B, and 40C show example phase drifts of an uncorrected SS-OCT signal associated with various noise sources. [Figure 40B] 40A, 40B, and 40C show example phase drifts of an uncorrected SS-OCT signal associated with various noise sources. [Figure 40C] 40A, 40B, and 40C show example phase drifts of an uncorrected SS-OCT signal associated with various noise sources.

[0068] [Diagram 41] 41A, 41B, 41C, and 41D show a simulation of the phase shift associated with patient movement.

[0069] [Diagram 42] 42A, 42B, 42C, and 42D show a simulation of the effect of A-scan time on the error resulting from phase shifts associated with patient motion.

[0070] [Figure 43A] 43A and 43B show the amplitude of typical patient movement. [Figure 43B] 43A and 43B show the amplitude of typical patient movement. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0071] While various embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the present invention described herein may be employed.

[0072] The miniature OCT system disclosed herein is well suited for use with many previous clinical tests, 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 thickness changes in the retina. Alerts are optionally sent to patients, caregivers, and healthcare providers when corrective action should be taken, such as medication changes, dosages, or reminders to take medication.

[0073] As used herein, the term "retinal thickness (RT)" refers to the thickness of the retina between layers used to assess the thickness of the patient's retina. RT may correspond, for example, to the thickness of the retina between the anterior surface of the retina 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. An optically detectable layer of the retina may, for example, comprise 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 are smaller in at least one linear dimension than structures that can be resolved by a lower resolution measurement system.

[0076] FIG. 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 by varying the size of the pupil 25, which allows the light to pass to the lens 30. The anterior chamber 40 contains aqueous humor 45, which determines the intraocular pressure (IOP). The lens 30 focuses light for imaging. The focusing 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 humor 55. The vitreous humor maintains the overall shape and structure of the eye. The light then passes toward the retina 60, which has a light-sensitive area. In particular, the macula 65 is the area of ​​the retina responsible for receiving light at the center of the visual surface. Within the macula, the fovea 70 is the area of ​​the retina that is most sensitive to light. Light passing toward the retina generates electrical signals that are passed to the optic nerve 80 and then to the brain for processing.

[0077] Several disorders result in a reduction in the optical performance of the eye. In some cases, the intraocular pressure (IOP) is either too high or too low. This is caused, for example, by too high or too low production rates of aqueous humor in the anterior chamber. In other cases, the retina is too thin or too thick. This occurs, for example, due to fluid accumulation in the retina. Diseases associated with abnormal retinal thickness (RT) include, for example, glaucoma and macular edema. In some cases, the healthy range of RT is 175 μm thick to 225 μm thick. In general, 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. It is therefore desirable to have a 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) to measure RT or RLT at multiple time points. 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. As another example, a patient measures their RT or RLT at multiple time points to track their response to a drug or other treatment. In some cases, the system generates an alert when one or more recent measurements of RT or RLT deviate significantly from a previous measurement. In some cases, the system alerts the patient or the patient's physician to the change. In some cases, this information is used to schedule a follow-up appointment between the patient and physician, for example, to attempt to treat the ophthalmic disease, to discontinue a prescribed treatment, or to perform additional testing.

[0079] FIG. 2 shows a schematic diagram of a system that allows a patient to measure RT or RLT at multiple time points and communicate the results, according to some embodiments. The patient looks into a handheld OCT device 100 and obtains a measurement of RT or RLT. In some embodiments, the handheld OCT device includes an optical system 102, electronics 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 some cases, the transmitter is a wireless transmitter. In some cases, the handheld OCT device communicates the results via a wireless communication channel 110 to a mobile patient device 120 on the patient's smartphone or other portable electronic device. 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 of skill in the art.

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

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

[0083] In some cases, the patient mobile device communicates the results of the measurements 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 still other cases, the wireless communication is via any other wireless communication known to those of skill in the art. In specific embodiments, the wireless communication means is configured to enable transmission to or receipt 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 to a patient device 150 on the patient's computer, tablet, or other electronic device via a first communication channel 132. In some embodiments, the results are transmitted to a physician device 160 on the physician's computer, tablet, or other electronic device via a second communication channel 134. In some cases, the results are transmitted to an analysis device 170 on another user's computer, tablet, or other electronic device via a third communication channel 136. In some embodiments, the results are transmitted to a patient management system or hospital management system 180 via a fourth communication channel 138. 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 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 still other cases, the communication is via Wi-Fi. In still other cases, 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 receipt from a cloud-based or other network-based storage and communication system. In some cases, the first communication channel is configured to allow only receipt 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 still other embodiments, 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 receipt from a cloud-based or other network-based storage and communication system. In some embodiments, the second communication channel is configured to allow only receipt from a cloud-based or other network-based storage and communication system.

[0087] In specific cases, the third communication channel is 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 still other cases, the communication is via Wi-Fi. In still other cases, 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 allow 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 allow only reception from a cloud-based or other network-based storage and communication system.

[0088] In some embodiments, the fourth communication channel is 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 still other cases, the communication is via Wi-Fi. In still other cases, 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 only reception 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 the handheld OCT device. In some cases, the determination of RT or RLT is performed at a location near 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 some cases, 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 the RT or RLT measurement on the patient device 150. In some cases, the results include an alert 152 that alerts the patient that the result of the measurement is outside of the normal or healthy range. In some cases, the results also include a display of the measurement 154. For example, in one case, the RT or RLT measurement produces a result of 257 μm. This result is outside of the normal or healthy range. In some cases, this causes the system to generate an alert and display the measurement of 257 μm on the patient app. In a specific case, the results also include a chart 156 that shows the patient's RT or RLT history over multiple time points. 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 physician. 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 the physician. In other cases, the instructions include more information. In yet other cases, the instructions include less information.

[0091] In some embodiments, the patient's physician receives the results and analysis of the RT or RLT measurement on the physician device 160. In some cases, the results include an alert 162 that alerts the physician that the result of the measurement is outside of the normal or healthy range. In some cases, the results also include an alert 164 that informs the physician that the patient's measurement is outside of the normal or healthy range. In some embodiments, the alert includes a suggestion that the physician call the patient, schedule an appointment, or provide medical assistance. In some embodiments, the results also include a display 166 that shows the most recent and historical measurements for each of the physician's patients. For example, in one case, the RT or RLT measurement produces a result of 257 μm. This result is outside of the normal or healthy range. In some cases, this causes the system to generate an alert and display the measurement of 257 μm on the physician app. In a specific case, 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 the RT or RLT measurements on the analysis device 170. In some cases, 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 nursing facility. To protect patient privacy, in some cases the analysis device is restricted to receiving only a subset of a given patient's information. For example, the subset is restricted to not include any personally identifiable information about a given patient. In some cases, the results include an alert 172 that warns that a large number of abnormal or unhealthy measurements have been taken within a particular time 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 anonymous patient data, such as age, sex, genetic information, information about the patient's environment, smoking history, other diseases the patient suffers from. In some cases, the results and analysis include anonymous treatment plans for the patient, such as a list of prescribed medications, treatment history, etc. In some cases, the results and analysis include measurements, such as results of RT or RLT measurements, visual function tests, or patient compliance with a course of treatment. In some cases, the results and analysis include data from an electronic medical record. In some cases, the results and analysis include diagnostic information from a visit to a patient's health care provider, such as results of an OCT scan obtained by the patient's health care provider.

[0094] In some embodiments, the patient's clinical, hospital, or other healthcare provider receives the results and analysis of the 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 allows the provider to update the treatment plan for the patient. In some cases, the results and analysis allow the provider to decide to call the patient for early outpatient care. In some cases, the results and analysis allow the provider to decide to postpone outpatient care.

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

[0096] FIG. 3A illustrates a handheld OCT device utilizing short-range wireless communication, according to some embodiments. In some embodiments, the handheld OCT device 100 includes an optical system 102, electronics 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 individual designated by the patient, opens the 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 a Bluetooth® channel to a mobile patient device 120 on the patient's smartphone or other portable electronic device.

[0097] In one instance, the results include an alert 122 that alerts the patient that the result of the measurement is outside of the normal or healthy range. In a specific embodiment, the results also include a display of the measurement value 124. For example, a measurement of RT or RLT may in one case produce a result of 257 μm. This result is outside of the normal or healthy range. In one case, this causes the system to generate an alert and display the measurement value of 257 μm on the patient mobile app. In a specific embodiment, the results also include a chart 126 that shows the patient's RT or RLT history over multiple time points.

[0098] In some cases, the patient mobile device communicates the results of the measurements 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 over a secure Wi-Fi channel. In still other cases, the wireless communication is over a cellular network. In a specific embodiment, the cellular network is a secure cellular network. In other embodiments, the transmitted information is encrypted. In some cases, the communication channel is configured to allow transmission to or receipt 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 individual designated by the patient, when too much time has passed since the Patient Mobile Device was last opened. For example, in some cases, this notification occurs because the patient has not acquired RT or RLT measurements in the recent past 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 the results of too many measurements and needs to transmit the data 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] FIG. 3B illustrates 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, according to some embodiments. In some embodiments, the handheld OCT device 100 includes an optical system 102, electronics 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 a specific case, the wireless communication is via a GSM wireless communication channel. In other embodiments, the system utilizes third generation (3G) or fourth generation (4G) mobile communication standards. In such cases, the wireless communication is via a 3G or 4G communication channel.

[0101] In specific embodiments, the patient mobile device 120 receives the results of the measurements 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 the cloud-based or other network-based storage and communication system.

[0102] Once retrieved from the cloud-based or other network-based storage and communication system, the results of the RT or RLT measurement are, in some instances, viewable on the patient mobile app. In some instances, the results include an alert 122 that alerts the patient that the result of the measurement is outside of a normal or healthy range. In some instances, the results also include a display of the measurement value 124. For example, in one instance, the RT or RLT measurement produces a result of 257 μm. This result is outside of a normal or healthy range. In a specific embodiment, this causes the system to generate an alert and display the measurement value of 257 μm 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 time points.

[0103] In some cases, the Patient Mobile Device has a feature that notifies the patient, or another individual designated by the patient, when too much time has passed since the Patient Mobile Device was last opened. For example, in some cases, this notification occurs because the patient has not acquired RT or RLT measurements in the recent past 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 the results of too many measurements and needs to transmit the data 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, the handheld OCT device is equipped with 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 the patient mobile device on a smartphone or other portable electronic device through 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 through a GSM, 3G, or 4G wireless communication channel. In specific cases, the cloud-based system then communicates with the patient mobile device through Wi-Fi, cellular, or other wireless communication channels. Alternatively, the Bluetooth transmitter is built into the docking station. In some cases, this allows for the use of older devices for patients lacking a smartphone. In some cases, the docking station also includes a means for charging the battery of the handheld OCT device.

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

[0106] The optical components described herein can be miniaturized to provide a handheld OCT device with a reduced physical size and mass as described herein, as will be understood by one of ordinary skill in the art.

[0107] In many embodiments, the handheld OCT device of FIGS. 3A and 3B is small enough and lightweight enough to be easily operated with one hand of a 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 distance traversed in the range of about 80 mm to about 160 mm. In specific embodiments, the device has a maximum distance traversed 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 distance traversed comprises a 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 within the range of about 55 mm to about 65 mm.

[0108] FIG. 4 shows a schematic diagram of information flow in a handheld OCT system according to some embodiments. In some cases, the handheld OCT device 400 further comprises a subsystem for measuring RT or RLT 402 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 the 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 app 412.

[0109] In some cases, the computing device transmits the patient data and the 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 instances, the cloud-based or other network-based storage system further comprises any of 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 a hospital management system.

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

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

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

[0113] In some embodiments, the cloud-based or other network-based storage and communication system further comprises a measurement and treatment storage system. In some cases, the measurement and treatment storage system is configured to transmit the measurement data to any of the mobile API, the patient app, the physician app, and the analytics app. In some cases, the measurement and treatment storage system is configured to receive the measurement data from any of the mobile API, the patient app, the physician app, and the analytics app.

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

[0115] The handheld OCT device may 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 instances, the handheld OCT device utilizes spatially encoded frequency-domain OCT. In some cases, the handheld OCT device utilizes time-encoded frequency-domain OCT, also known as swept-source OCT (SS-OCT).

[0116] FIG. 5 shows a schematic diagram of the optical system of a swept-source optical coherence tomography (SS-OCT) device, according to some embodiments. In some cases, the optical system 102 includes a light source 500, a beam splitter 510, front-end optics 520, a reference mirror 530, and a processing unit 540. In some embodiments, the processing unit further includes a photodetector 542 and a signal processing module 544. Light from the light source impinges on the beam splitter. A portion of the light is directed along a reference arm to the reference mirror, and a portion of the light is directed to the front-end optics and then to the sample 550. In some cases, the sample comprises the eye. In some cases, the sample comprises the retina. In some embodiments, the retina comprises several layers of tissue. In some cases, the layers of tissue comprise a layer 552 of light-sensitive rod and cone cells, a retinal pigment epithelium (RPE) 554, and a choroid 556. In other cases, the layers of tissue consist of other layers of the retina, such as the nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner limiting membrane, outer limiting membrane, and / or Bruch's membrane. Light is reflected back to the device at each boundary of each of the layers. 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 at a photodetector. In some cases, the light is reflected from the posterior surface of the layer of rod and cone cells, the anterior surface of the layer of rod and cone cells, 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 may be reflected from any surface of any other layer, such as the nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, outer limiting membrane, and / or retinal pigment epithelium. In some cases, the RLT corresponds to the thickness of any of these retinal layers, or the thickness between any two such layers.

[0117] This process is repeated over the range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength and attains a maximum when the light reflected from the boundary and the light reflected from the reference mirror are in phase, or when the light reflected from the boundary is in phase with the light reflected from another boundary. This condition is attained at one or more specific wavelengths of light per boundary and is characterized by one or more maxima of the interference signal. At other wavelengths, the interference signal exhibits partial constructive interference 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 comprises peaks corresponding to the interference signals associated with the thicknesses of various retinal layers. In some embodiments, SS-OCT utilizes a light source with a relatively long coherence length (typically greater than 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 peaks 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 wavelength that can be tuned. In some cases, the laser source is scanned across a range of wavelengths to obtain an OCT signal. In some cases, the laser source can be rapidly scanned to allow for 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 a current provided 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 provided with a sinusoidally varying current to generate a sinusoidally varying wavelength.

[0119] In some embodiments, the VCSEL is a commercially available VCSEL. In some cases, the VCSEL is a VCSEL that is modified from a commercially available VCSEL based on the teachings described herein. In some cases, the VCSEL is a VCSEL obtained from a manufacturer 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 one of ordinary skill in the art.

[0120] In some cases, the VCSEL has a maximum recommended current for continuous or pulsed use. In some cases, the maximum continuous current rating limits the range of wavelengths over which the VCSEL can be swept. For example, the 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 embodiments, the wavelength emitted by the VCSEL varies linearly with the operating current with a proportionality constant of 0.3 nm / mA. In some cases, this limits the range of wavelengths over which the VCSEL can be swept 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 obtainable axial resolution of the VCSEL-based SS-OCT device. Assuming a Gaussian spectrum from the light source, the obtainable axial resolution is determined according to the following:

number

[0121] Thus, 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, the VCSEL emits an optical intensity of less than or equal to 0.01 mW, 0.025 mW, 0.05 mW, 0.1 mW, 0.25 mW, 0.5 mW, 1 mW, 2.5 mW, 5 mW, 10 mW, 25 mW, 50 mW, 100 mW, 250 mW, 500 mW, 1 W, 2.5 W, 5 W, 10 W, 25 W, 50 W, or 100 W.

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

[0123] Although Table 1 references a central wavelength of 850 nm, one of skill in the art can follow the disclosure provided herein to construct a compact OCT system that operates at a different central wavelength with a similar sweep range and similar resolution. Also, one of skill in the art can readily 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, additional VSCELs are used to extend the swept wavelength range as described herein.

[0125] In some cases, the limited operating range of VCSELs also limits the ability to extract information from the OCT signal due to the limited phase shift imparted by the 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 given by:

number

[0126] In some cases, it is useful to extract frequency information from the interference signal resulting from the interaction of light reflected from a first interface and light reflected from a second interface. To extract this information, it can be useful to acquire two signal periods of the interferogram. This corresponds to a phase shift of 4π. Thus, a VCSEL has a minimum range of wavelengths Δλ given by: min It should work for

number

[0127] Thus, in some cases, the limited operating range of a VCSEL, for example, limits the ability to obtain sufficient phase shifts to extract frequency information from an interference signal. In some embodiments, for 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 the retina, the minimum range of wavelengths is 3.7 nm. In some cases, this range of wavelengths typically exceeds the range of wavelengths emitted by a VCSEL operated within its maximum recommended current for continuous use. Thus, in some cases, it is useful to extend the range of wavelengths emitted by a VCSEL to generate sufficient phase shifts.

[0128] The light source need not be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous emission (ASE). In some cases, the light source is a superluminescent diode (SLD). Additionally, in some embodiments, the light source comprises multiple light sources.

[0129] In some cases, the front-end optics comprises an optical element such as a lens. In some embodiments, the front-end optics comprises any reflective, refractive, or diffractive element. In some cases, the front-end optics comprises two or more reflective, refractive, or diffractive elements. In some cases, the front-end optics comprises an electro-optic, magneto-optic, acousto-optic, or mechano-optic device. In some embodiments, the front-end optics comprises any optical element known to one of skill in the art.

[0130] In some embodiments, the front-end optics comprises 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 cases, determining RT or RLT at different locations on the retina further allows the location of the fovea to be confirmed. In some embodiments, the scanning optical element is selected from the group consisting of a mirror, multiple 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. In some cases, the scanning optical element comprises any scanning optical element as known to one of skill in the art.

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

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

[0133] This process is repeated over the range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength and attains a maximum when the light reflected from a boundary is in phase with the light reflected from another boundary. This condition is attained at one or more specific wavelengths of light for each boundary and is characterized by one or more maxima of the interference signal. At other wavelengths, the interference signal exhibits 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 comprises peaks corresponding to the wavelengths associated with the interference maxima for each boundary. In some embodiments, SS-OCT utilizes a light source with a relatively long coherence length (typically greater than 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 peaks indicates the thickness of each layer of tissue.

[0134] In some cases, the light source comprises a laser source. In some embodiments, the laser source generates laser light having a wavelength that can be tuned. In some cases, the laser source is scanned across a range of wavelengths to obtain an OCT signal. In some cases, the laser source can be rapidly scanned to allow for 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 a current provided to the VCSEL. In some cases, the VCSEL is continuously scanned across a range of wavelengths by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a range of wavelengths by periodically varying the current. For example, the VCSEL can be provided with a sinusoidally varying current to generate a sinusoidally varying wavelength.

[0135] In some embodiments, the front-end optics comprises an optical element such as a lens. In some cases, the front-end optics comprises any reflective, refractive, or diffractive element. In some cases, the front-end optics comprises two or more reflective, refractive, or diffractive elements. In some embodiments, the front-end optics comprises an electro-optic, magneto-optic, acousto-optic, or mechano-optic device. The front-end optics may comprise any optical element known to one of ordinary skill in the art.

[0136] FIG. 6B illustrates the wavelength range over which a VCSEL operates in a swept-source optical coherence tomography (SS-OCT) device lacking a reference mirror, according to some 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 over which the VCSEL can be swept. 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 wavelength emitted by the 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 over which the VCSEL can be swept 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 obtainable axial resolution of the VCSEL-based SS-OCT device.

[0137] Thus, in some cases, the limited operating range of the 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 an optical intensity of less than or equal to 0.01 mW, 0.025 mW, 0.05 mW, 0.1 mW, 0.25 mW, 0.5 mW, 1 mW, 2.5 mW, 5 mW, 10 mW, 25 mW, 50 mW, 100 mW, 250 mW, 500 mW, 1 W, 2.5 W, 5 W, 10 W, 25 W, 50 W, or 100 W.

[0138] The light source need not be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous emission (ASE). In some cases, the light source is a superluminescent diode (SLD). Additionally, 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 VCSELs allows the SS-OCT device to have achievable axial resolution values ​​of less than about 100 μm.

[0140] FIG. 7A shows a schematic diagram of the optical system of a swept-source optical coherence tomography (SS-OCT) device utilizing a reference mirror, according to some embodiments. In some cases, the optical system 102 includes a VCSEL or other light source 700, a beam splitter 710, front-end optics 720, a reference mirror 730, and a processing unit 740. In some embodiments, the processing unit further includes a photodetector 742 and a signal processing module 744. Light from the light source impinges on the beam splitter. A portion of the light is directed along the reference arm to the reference mirror, and a portion of the light is directed to the front-end optics and then to the sample 750. The light is reflected back into 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 at the photodetector.

[0141] This process is repeated over the range of wavelengths emitted by the light source. The amplitude of the interference signal varies with wavelength and attains a maximum when the light reflected from the boundary and the light reflected from the reference mirror are in phase, or when the light reflected from the boundary is in phase with the light reflected from another boundary. This condition is attained at one or more specific wavelengths of light for each boundary and is characterized by one or more maxima of the interference signal. At other wavelengths, the interference signal exhibits 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 comprises peaks corresponding to the wavelengths associated with the interference maxima for each boundary. In some cases, SS-OCT utilizes a light source with a relatively long coherence length (typically more than a few millimeters). In some embodiments, the amplitude of the interference signal decreases as the distance between the two retinal layers increases. In some cases, the location 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 the effect of shifting the frequency, where the maximum interference signal is obtained at a higher frequency. In some embodiments, this shift to a higher frequency allows for 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 wavelength that can be tuned. In some cases, the laser source is scanned across a range of wavelengths to obtain an OCT signal. In some cases, the laser source can be rapidly scanned to allow for 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 a current provided to the VCSEL. In some cases, the VCSEL is continuously scanned across a range of wavelengths by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a range of wavelengths by periodically varying the current. For example, the VCSEL can be provided with a sinusoidally varying current to generate a sinusoidally varying wavelength.

[0143] In some embodiments, the front-end optics comprises an optical element such as a lens. In some cases, the front-end optics comprises any reflective, refractive, or diffractive element. In some cases, the front-end optics comprises two or more reflective, refractive, or diffractive elements. In some embodiments, the front-end optics comprises an electro-optic, magneto-optic, acousto-optic, or mechano-optic device. The front-end optics may comprise any optical element known to one of ordinary skill in the art.

[0144] In some cases, the front-end optics includes a scanning optical element as described herein.

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

[0146] FIG. 7C shows how the 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 the reference mirror, the OCT peak of a given sample is obtained at a relatively low frequency, indicated by t (encoded). This frequency corresponds to the optical path difference in the sample. The presence of the reference mirror has the effect that each boundary of the sample interferes with the reference mirror. For a sample with two boundaries, this effect gives rise to two relatively high frequency components in the OCT signal, represented as d (encoded) and d+t (encoded) in FIG. 7C. The difference between these two frequencies corresponds to the distance between the boundaries of the sample. For the retina or retinal layer, the difference therefore corresponds to the RT or RLT, respectively.

[0147] 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 over which the VCSEL can be swept. 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 wavelength emitted by the VCSEL varies 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 over which the VCSEL can be swept. 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 obtainable axial resolution of the VCSEL-based SS-OCT device. In some embodiments, the sweep range is increased by driving a current beyond the maximum current rating, as described herein.

[0148] Thus, 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, the VCSEL emits an optical intensity of less than or equal to 0.01 mW, 0.025 mW, 0.05 mW, 0.1 mW, 0.25 mW, 0.5 mW, 1 mW, 2.5 mW, 5 mW, 10 mW, 25 mW, 50 mW, 100 mW, 250 mW, 500 mW, 1 W, 2.5 W, 5 W, 10 W, 25 W, 50 W, or 100 W.

[0149] The light source need not be a VCSEL. In some cases, the light source is a doped fiber amplifier that utilizes amplified spontaneous emission (ASE). In some cases, the light source is a superluminescent diode (SLD). Additionally, in some embodiments, the light source comprises multiple light sources.

[0150] In some cases, the limited obtainable axial resolution is improved by utilizing two or more VCSELs or other light sources in the SS-OCT system. In some embodiments, each of the two or more VCSELs or other light sources has an emission spectrum that is distinct from the emission spectrum of each of the other VCSELs or other light sources. In some cases, the emission spectra of the two or more VCSELs partially overlap. In some 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 combine to produce a wider range of emission wavelengths for the SS-OCT measurements. In some cases, this enhances the obtainable axial resolution of the SS-OCT measurements.

[0151] FIG. 8A illustrates the optical system of a swept-source optical coherence tomography (SS-OCT) device utilizing two VCSELs and lacking a reference mirror at a first particular time point according to some embodiments. In some cases, the optical system 102 includes 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, front-end optics 820 as described herein, and a processing unit 840. In some embodiments, the processing unit further includes a photodetector 842 and a signal processing module 844. Light from the first light source impinges on the beam splitter. The light is directed to the front-end optics and then to the sample 850. In some cases, at the first particular time point, the first VCSEL or other light source is on (sending laser light to the sample) while the second VCSEL or other light source is off (not sending laser light to the sample). Light is reflected back into 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 at a photodetector.

[0152] 8B shows a schematic diagram of a swept-source optical coherence tomography (SS-OCT) device utilizing two VCSELs and lacking a reference mirror at a second particular time point according to some embodiments. In one instance, at the second particular 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 reflected back into 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 boundary of the second layer. The interference signal is detected at a photodetector.

[0153] This process is repeated over the range of wavelengths emitted by the first and second light sources. The amplitude of the interference signal varies with wavelength and attains a maximum when the light reflected from the boundary and the light reflected from the reference mirror are in phase, or when the light reflected from the boundary is in phase with the light reflected from another boundary. This condition is attained at one or more specific wavelengths of light per boundary and is characterized by one or more maxima of the interference signal. At other wavelengths, the interference signal exhibits 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 comprises peaks corresponding to the wavelengths associated with the interference maxima per 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 interference maxima. In some embodiments, this results in narrow peaks in the frequency spectrum, and in some cases 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 wavelength that can be tuned. In some cases, the laser source is scanned across a range of wavelengths to obtain an OCT signal. In some cases, the laser source can be rapidly scanned to allow for 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 a current provided to the VCSEL. In some cases, the VCSEL is continuously scanned across a range of wavelengths by continuously varying the current. In some embodiments, the VCSEL is periodically scanned across a range of wavelengths by periodically varying the current. For example, the VCSEL can be provided with a sinusoidally varying current to generate a sinusoidally varying wavelength.

[0155] In some embodiments, the front-end optics comprises an optical element such as a lens. In some cases, the front-end optics comprises any reflective, refractive, or diffractive element. In some cases, the front-end optics comprises two or more reflective, refractive, or diffractive elements. In some embodiments, the front-end optics comprises an electro-optic, magneto-optic, acousto-optic, or mechano-optic device. In some cases, the front-end optics comprises any optical element known to one of skill in the art.

[0156] In some cases, the front-end optics 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 cases, 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 as known to one of skill in the art.

[0157] FIG. 8C illustrates the wavelength range over which a VCSEL operates in a swept-source optical coherence tomography (SS-OCT) device utilizing two VCSELs and lacking a reference mirror, according to some embodiments.

[0158] The wavelength sweep can be coordinated between two or more VCSELs or other light sources in various manners. In one embodiment, a first VCSEL or other light source is swept across its wavelength range while a second VCSEL or other light source is off. The second VCSEL or other light source is then swept across its wavelength range while the first VCSEL or other light source is off. The wavelength sweep alternates 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 VCSEL is swept at a rate between about 50 Hz and about 10 kHz. In some cases, the VCSEL is swept at a rate between about 1 kHz and about 5 kHz.

[0159] In another embodiment, two or more VCSELs undergo their wavelength sweep at the same time and at the same rate. In such a setup, it may be useful to remove temporal correlation between the OCT signal resulting from the first VCSEL or other light source and the OCT signal resulting from the second VCSEL or other light source. This may be accomplished, for example, by modifying the optical setup of FIG. 8A to include a spectrometer instead of a photodetector, as would be readily understood by one of ordinary skill 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 their wavelength sweep simultaneously, but at different rates. For example, a first VCSEL or other light source may be swept across its range of emission wavelengths at a first rate to complete its wavelength sweep in a first amount of time. A second VCSEL or other light source is swept across its range of emission wavelengths at a second rate different from the first rate to complete its wavelength sweep in a second amount of time different from the first amount of time. In this manner, the SS-OCT signal resulting from the first VCSEL or other light source is temporally encoded in a manner different from the temporal encoding of the SS-OCT signal resulting from the second VCSEL or other light source. The SS-OCT signal resulting from the first VCSEL or other light source is then differentiated from the SS-OCT signal resulting 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 includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 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 over which each VCSEL can be swept. 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 over which each VCSEL can be swept 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, a combination of 2, 3, 4, 5, 6, 7, 8, 9, 10, or more VCSELs or other light sources produces a full range of wavelengths up to 30 nm or more. In some cases, the use of multiple VCSELs allows for a swept wavelength range within, for example, 5 nm to 10 nm.

[0162] Thus, in some cases, the wider total operating range of 2, 3, 4, 5, 6, 7, 8, 9, 10 or more VCSELs enhances the obtainable axial resolution. In some embodiments, for a set of two VCSELs, each with a central operating wavelength of about 850 nm, the obtainable axial resolution is 53 μm when each VCSEL has a 3.0 nm operating range. With three VCSELs, the obtainable axial resolution is 35 μm when each VCSEL has a 3.0 nm operating range. With four VCSELs, the obtainable axial resolution is 27 μm when each VCSEL has a 3.0 nm operating range. In some cases, the obtainable axial resolution is further enhanced with an increasing number of VCSELs. In some embodiments, each VCSEL emits an optical intensity of less than or equal to 0.01 mW, 0.025 mW, 0.05 mW, 0.1 mW, 0.25 mW, 0.5 mW, 1 mW, 2.5 mW, 5 mW, 10 mW, 25 mW, 50 mW, 100 mW, 250 mW, 500 mW, 1 W, 2.5 W, 5 W, 10 W, 25 W, 50 W, or 100 W.

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

[0164] FIG. 9 illustrates the operation of a VCSEL beyond its maximum current rating. In some cases, the current supplied to the VCSEL is varied over time according to a waveform 900. The waveform can be triangular, sinusoidal, or any other waveform known to one of skill 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 times in the waveform, the VCSEL is supplied with a current above the upper current threshold or 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 about 50 Hz and about 10 kHz. In some cases, the VCSEL is swept at a rate between about 1 kHz and about 5 kHz.

[0165] In some cases, exceeding the maximum current allows the VCSEL to be driven beyond its specified maximum wavelength range, which is 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 a plurality of measurements. There may be a delay implemented between successive measurements to avoid overheating of the VCSEL. 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 obtainable axial resolution provided by a single VCSEL with a limited working range does not pose a problem for the technique, including measuring the thickness of a particular structure, but not attempting to measure substructures within the structure. For example, one may be interested in obtaining RT or RLT measurements without concern for imaging substructures within the retina. Furthermore, one may be primarily interested in measured changes in RT or RLT. In some cases, it is possible to obtain RT or RLT measurements with greater precision than might be expected from the obtainable axial resolution.

[0167] FIG. 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 a layer of tissue and a second interference signal 1002 associated with light reflected from a second boundary of the layer of tissue. The interference signals 1000 and 1002 are represented in the frequency domain. The first signal has a maximum at an optical path difference Δz1. The second signal has a maximum at an optical path difference Δz2. Each of the signal peaks has an associated width. The first and second interference signals may be said to be resolved when the two signals do not completely overlap but provide identifiable 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 related to the range of wavelengths over which the SS-OCT light source is swept. Thus, for SS-OCT devices that utilize a relatively narrow range of wavelengths, the axial resolution may be less than ideal.

[0168] For measuring RT, the axial resolution should be sufficient to distinguish a first interference signal associated with a first interface of a layer of tissue and a second interference signal associated with a second interface of the layer of tissue. Because the retina typically has an RT greater than 150 μm, an SS-OCT device capable of measuring RT can achieve an axial resolution value of less than about 150 μm.

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

[0170] FIG. 10C shows a graphical representation of repeatability and reproducibility associated with measuring RT or RLT for a retina that does not exhibit a change in RT or RLT. At a first time point, the measurement of RT follows a distribution 1020 determined by the repeatability. At subsequent time points, the measurement of RT or RLT is taken from the distribution 1022 as determined by the repeatability and reproducibility. For 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 combined repeatability and reproducibility. However, if Δx exceeds the combined repeatability and reproducibility, an increase in retinal thickness is identified and reported to the patient and healthcare provider, for example, with an alert, as more fully described in FIG. 10D. In many embodiments, the miniature OCT device has a combined repeatability and reproducibility of less than about 35 μm. In some embodiments, the SS-OCT device has a combined repeatability and reproducibility of less than 25 μm with a 95% confidence level.

[0171] FIG. 10D shows a graphical representation of repeatability and reproducibility associated with measuring RT or RLT for a retina that has exhibited a change in RT or RLT. At a first time point, the RT or RLT is obtained within a first distribution 1030 determined by the repeatability. At a subsequent time point, the RT or RLT is obtained within a second distribution 1032 also determined by the repeatability. For a retina that has exhibited a change in RT or RLT, the two distributions 1030 and 1032 are no longer within close proximity of each other. When the distance between the two distributions 1030 and 1032 exceeds a 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 measurements are separated by more than a combination of repeatability and reproducibility. For example, this would be approximately 35 μm for a repeatability of 25 μm and a repeatability of 25 μm. Alternatively, with systematic errors or long-term drift, the compound error may be greater than 35 μm for a reproducibility of 25 μm and a repeatability of 25 μm. Thus, the peaks of the distribution for a first RT measurement of 150 μm and a second RT measurement of 200 μm will be 50 μm apart. Although the first and second measurements are shown to have non-overlapping distributions, the methods and apparatus described herein are capable of determining RT or RLT for partially overlapping distributions of measurements.

[0172] In some cases, the RT or RLT measurements obtained by the handheld OCT device are compared to a reference measurement. In some embodiments, the reference measurement is obtained from a measurement made by a clinical OCT device. In some cases, the reference measurement is obtained during a patient's visit with a healthcare provider. In some cases, the reference measurement is stored on the 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 the miniature OCT device, for example, to account for any systematic errors in the measurements.

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

[0174] In many embodiments, the miniature OCT system is calibrated to a specific patient using a high-resolution clinical OCT reference system that has a resolution value less than that of the miniature OCT system. For example, the patient can visit an ophthalmologist and the retinal thickness can be measured using a high-resolution ultrasound system in the clinic. The miniature OCT system can 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 continued operation after a drop. In some cases, the devices described herein are capable of surviving a drop during a drop test with a 95% survival rate. 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 continued operation after a drop test with a repeatable change of 30 μm or less. In some embodiments, the devices are capable of continued operation after a drop test with a repeatable change of 20 μm or less. In some embodiments, the devices are capable of continued operation after a drop test with a repeatable change of 15 μm or less. In some embodiments, the devices are capable of continued operation after a drop test with a repeatable change of 10 μm or less. In some embodiments, the devices are capable of continued operation after a drop test with a repeatable change of 5 μm or less.

[0176] 11 is a flow chart of a method for making repeated measurements of a patient's retinal thickness (RT) over time and noting changes that may correspond to undesirable outcomes. Method 1100 comprises 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 retinal thickness, repeating the measurements 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 described herein. In some cases, the patient data includes any of the patient's name, age, sex, height, weight, current ophthalmic problems, and current medical problems.

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

[0179] In step 1106, the handheld OCT device directs a beam of light into the patient's eye. The light is reflected off the boundaries of the various layers of 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 a photodetector. In some cases, the interference signal is generated by interference of the reflected light with light that has traversed a reference arm of the handheld OCT device. In some cases, the interference signal is generated by 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 to the eye and records an interference signal for each wavelength.

[0181] In step 1110, the RT or RLT of the patient is determined. In some cases, the RT or RLT is determined by a mathematical analysis of the OCT signal. For example, the RT or RLT may be determined from a Fast Fourier Transform of the OCT signal. The RT or RLT may be determined from any other frequency analysis of the OCT signal. The RT or RLT may be determined by comparing the frequency content of the OCT signal to a calibration curve that maps the RT or RLT to frequency. In some embodiments, the calibration curve is general to all patients. In some cases, the calibration curve is specific to an 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 measurements. 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 generated if the RT or RLT changes significantly or if the RT or RLT is outside of a normal or healthy range. In some cases, the alert comprises a notification displayed on a mobile patient device as described herein. In some embodiments, the alert may comprise 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 a visit to an ophthalmologist. In some embodiments, a second RT or RLT is measured within 1 to 20 days after the first measurement. In some cases, RT or RLT is measured daily for multiple days within a range of about 5 to about 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 of more than 20 days. A change in RT or RLT is determined in response to the baseline thickness and multiple subsequent thicknesses. In some cases, the change in RT or RLT is measured with a confidence interval of at least 90%, at least 95%, or at least 99%.

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

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

[0188] In step 1204, the handheld OCT receives light reflected from 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 interference of the reflected light with light that has traversed a reference arm of the handheld OCT device. In some cases, the interference signal is generated by 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 a photodetector.

[0190] In step 1208, the handheld OCT device varies the wavelength of light directed at the retina. For each wavelength, steps 1202, 1204, and 1206 are repeated. An interference signal is recorded for each wavelength.

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

[0192] In step 1212, the resulting peaks are fitted to a sine wave. In some cases, the fitting is via a non-linear least squares fitting. In some embodiments, the fitting is via any other fitting method known to those of skill in the art.

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

[0194] Those skilled 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 duplicated, and additional steps can be added, as appropriate. The methods of 1100 and 1200 can be combined. Some of the steps can include sub-steps. Some of the steps can be automatic and some of the steps can be manual. A processor as described herein can comprise one or more instructions for performing at least a portion of one or more steps of methods 1100 and / or 1200. (Digital Processing Device)

[0195] In some embodiments, the platform, system, medium, and method described herein includes the use of a digital processing device or the same. In further embodiments, the digital processing device includes one or more hardware central processing units (CPUs) or general purpose processing units (GPGPUs) that perform the functions of the device. In still further embodiments, the digital processing device further comprises an operating system configured to execute the 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 herein, suitable digital processing devices include, by way of 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 smart phones, tablet computers, personal digital assistants, video game consoles, and vehicles. Those skilled in the art will recognize that many smart phones are suitable for use with the systems described herein. 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 with the systems described herein. Suitable tablet computers include those with booklet, slate, and convertible configurations, as known to those skilled in the art.

[0197] In some embodiments, the digital processing device includes an operating system configured to execute executable instructions. An operating system is software, including programs and data, that manages the device's hardware and provides services for the execution of applications, for example. Those skilled in the art will recognize that suitable server operating systems include, by way of non-limiting examples, FreeBSD®, OpenBSD, NetBSD®, Linux®, Apple® Mac OS X Server®, Oracle® Solaris®, Windows® Server®, and Novell® NetWare®. Those skilled in the art will recognize that suitable personal computer operating systems include, by way of non-limiting examples, 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, by way of non-limiting examples, 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, by way of non-limiting examples, 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, by way of non-limiting examples, 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 temporarily or permanently store data or programs. In some embodiments, the device is a volatile memory and requires power to maintain the stored information. In some embodiments, the device is a non-volatile memory and retains the stored information when the digital processing device is not powered. In further embodiments, the non-volatile memory comprises a flash memory. In some embodiments, the non-volatile memory comprises a dynamic random access memory (DRAM). In some embodiments, the non-volatile memory comprises a ferroelectric random access memory (FRAM®). In some embodiments, the non-volatile memory comprises a phase change random access memory (PRAM). In other embodiments, the device is a storage device, including, by way of non-limiting examples, 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 a 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 still 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, by way of non-limiting examples, a mouse, a trackball, a trackpad, a joystick, a game controller, or a stylus. In some embodiments, the input device is a touch screen or a multi-touch screen. 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 a Kinect, Leap Motion, or equivalent. In still further embodiments, the input device is a combination of devices such as those disclosed herein.

[0201] 13, in a particular embodiment, an 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 the present disclosure, such as, for example, performing processing steps. In this embodiment, 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), an electronic storage unit 1315 (e.g., hard disk), a communication interface 1320 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 1325, such as cache, other memory, data storage, and / or electronic display adapters. The memory 1310, the storage unit 1315, the interface 1320, and the peripheral devices 1325 communicate with the CPU 1305 through a communication bus (solid lines) such as a motherboard. The storage unit 1315 can be a data storage unit (or data repository) for storing data. The digital processing device 1301 can be operatively coupled to a computer network ("network") 1330 with the help of the communication interface 1320. The network 1330 can be the Internet, the Internet and / or an extranet, or an intranet and / or an extranet that communicates with the Internet. The network 1330, in some cases, is a telecommunications and / or data network. The network 1330 can include one or more computer servers, which can enable distributed computing such as cloud computing. The network 1330 can implement a peer-to-peer network, which, in some cases, can enable devices coupled to the device 1301 to behave as clients or servers with the help of the device 1301.

[0202] Continuing to refer to FIG. 13, the CPU 1305 can execute a series of machine-readable instructions, which may be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 1310. The instructions may be directed to the CPU 1305, which may then program or otherwise configure the CPU 1305 to implement the methods of the present disclosure. Examples of operations performed by the CPU 1305 may include fetch, decode, execute, and writeback. The CPU 1305 may be part of a circuit, such as an integrated circuit. One or more other components of the 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 FIG. 13, the storage unit 1315 can store files such as drivers, libraries, and saved programs. The storage unit 1315 can store user data, such as user preferences and user programs. The digital processing device 1301 can include one or more additional data storage units, in some cases external, such as located on a remote server communicating through an intranet or the Internet.

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

[0205] Methods as described herein may be implemented via machine (e.g., computer processor) executable code stored on electronic storage locations of the digital processing device 1301, such as, for example, on the memory 1310 or electronic storage unit 1315. The machine executable or machine readable code may be provided in the form of software. In use, the code may be executed by the processor 1305. In some cases, the code may be read from the storage unit 1315 and stored on the memory 1310 for easy access by the processor 105. In some circumstances, the electronic storage unit 1315 may be omitted and the machine executable instructions are stored on the memory 1310.

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

[0207] (Computer Program) In some embodiments, the platform, system, medium, and method disclosed herein include the use of at least one computer program or the same. A computer program includes a set of instructions executable in a CPU of a digital processing device, which is written to perform a specified task. Computer-readable instructions can be implemented as program modules, such as functions, objects, application programming interfaces (APIs), data structures, and the like, that perform a particular task or implement a particular abstract data type. In light of the disclosure provided herein, those skilled in the art will recognize that computer programs can be written in various versions of various languages.

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

[0209] (Web Applications) In some embodiments, the computer program comprises a web application. Given the disclosure provided herein, one of ordinary skill in the art will recognize that web applications, in various embodiments, utilize one or more software frameworks and one or more database systems. In some embodiments, the web application is created 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, by way of non-limiting examples, relational, non-relational, object-oriented, associative, and XML database systems. In further embodiments, suitable relational database systems include, by way of non-limiting examples, Microsoft® SQL Server, mySQL TM, and Oracle®. Those skilled in the art will also recognize that web applications, in various embodiments, are written in one or more versions of one or more languages. Web applications may be written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some embodiments, web applications are 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, web applications are written to some extent in a presentation definition language such as Cascading Style Sheets (CSS). In some embodiments, web applications are written to some extent in a client-side scripting language such as Asynchronous Javascript and XML (AJAX), Flash Actionscript, Javascript, or Silverlight®. In some embodiments, the web application may be implemented in any programming language, including, to some extent, Active Server Pages (ASP), ColdFusion®, Perl, Java®, Java® Server Pages (JSP), Hypertext Preprocessor (PHP), Python TM, Ruby, Tcl, Smalltalk, WebDNA, or Groovy. In some embodiments, the web application is written, in part, in a database query language, such as 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 a number of suitable multimedia technologies, including, by way of non-limiting examples, Adobe® Flash®, HTML 5, Apple® QuickTime®, Microsoft® Silverlight®, Java®, and Unity®.

[0210] (Mobile Application) In some embodiments, the computer program comprises a mobile application that is provided to the 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 disclosure provided herein, mobile applications are created by techniques known to those of skill in the art, using hardware, languages, and development environments known in the art. Those skilled in the art will recognize that mobile applications are written in a number of languages. Suitable programming languages ​​include, by way of non-limiting examples, C, C++, C#, Objective-C, Java, Javascript, Pascal, Object Pascal, Python. TM, 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 include, by way of non-limiting example, Airplay SDK, alcheMo, Appcelerator®, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments are available free of charge, including, by way of non-limiting example, Lazarus, MobiFlex, MoSync, and Phonegap. Mobile device manufacturers also provide SDKs for the iPhone® and iPad® (iOS), Android, and iOS® (Android) platforms, by way of non-limiting example. TM The Company distributes software developer kits, including the SDK, BlackBerry SDK, BREW SDK, Palm OS SDK, Symbian SDK, webOS SDK, and Windows Mobile SDK.

[0213] Those skilled in the art will recognize that several commercial forums are available for distribution of mobile applications, including, by way of non-limiting examples, the Apple® App Store, Google® Play, Chrome WebStore, BlackBerry® App World, App Store for Palm devices, App Catalog for webOS, Windows® Marketplace for mobile, 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 that is launched as an independent computer process that is not an add-on, e.g., not a plug-in, to an existing process. Those skilled in the art will recognize that standalone applications are often compiled. A compiler is a computer program that converts source code written in a programming language into binary object code, such as assembly language or machine code. Suitable compiled programming languages ​​include, by way of non-limiting examples, C, C++, Objective-C, COBOL, Delphi, Eiffel, Java, Lisp, Python. TM , Visual Basic, and VB.NET, or a combination thereof. Compilation is often performed at least in part to create an executable program. In some embodiments, a computer program includes one or more executable compiled applications.

[0215] (Web browser plug-in) In some embodiments, the computer program includes a web browser plug-in (e.g., an extension, etc.). In computing, a plug-in is one or more software components that add specific functionality to a larger software application. Makers of software applications support plug-ins to allow third party developers to create the ability to extend the application, support easy addition of new features, and reduce the size of the application. When supported, plug-ins allow customization of the functionality of the software application. For example, plug-ins are commonly used in web browsers to play video, generate interactivity, scan for viruses, and display specific file types. Those skilled in the art will be familiar with the use of plug-ins in Adobe® Flash® and other applications that use plug-ins to perform various functions, such as: Users will be familiar with several web browser plug-ins, including Microsoft® Player, 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, tool bands, or desk bands.

[0216] In light of the disclosure provided herein, one of skill in the art will be able to easily implement a number of programming languages, including, by way of non-limiting examples, C++, Delphi, Java, PHP, Python, TM It will be appreciated that several plug-in frameworks are available that allow for the development of plug-ins in a variety of programming languages, including Visual Basic .NET, Visual Basic .NET Framework 2.0, Visual Basic .NET Framework 3.0, Visual Basic .NET Framework 4.0, Visual Basic .NET Framework 5.0, Visual Basic .NET Framework 6.0, Visual Basic .NET Framework 7.0, Visual Basic .NET Framework 8.0, Visual Basic .NET Framework 9.0, Visual Basic .NET Framework 10.0, Visual Basic .NET Framework 11.0, Visual Basic .NET Framework 12.0, Visual Basic .NET Framework 13.0, Visual Basic .NET Framework 14.0, Visual Basic .NET Framework 15.0, Visual Basic .NET Framework 16.0, Visual Basic .NET Framework 17.0, Visual Basic .NET Framework 18.0, Visual Basic .NET Framework 19.0, Visual Basic .NET Framework 20.0

[0217] A web browser (also called an Internet browser) is a software application designed for use with network-connected digital processing devices to read, present, and traverse information resources on the World Wide Web. Suitable web browsers include, by way of non-limiting example, Microsoft® Internet Explorer®, Mozilla® Firefox®, Google® Chrome, Apple® Examples of suitable mobile web browsers include Safari, Opera Software, Opera, and KDE Konqueror. In some embodiments, the 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, including, by way of non-limiting examples, handheld computers, tablet computers, netbook computers, subnotebook computers, smartphones, music players, personal digital assistants (PDAs), and handheld video game systems. Suitable mobile web browsers include, by way of non-limiting examples, Google Android browser, 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 a browser.

[0218] (Software Module) In some embodiments, the platforms, systems, media, and methods disclosed herein include the use of software, server, and / or database modules, or the same. In light of the disclosure provided herein, the software modules are created by techniques known to those of skill in the art using machines, software, and languages ​​known to those of skill in the art. The software modules disclosed herein are implemented in numerous ways. In various embodiments, the software modules comprise files, sections of code, programming objects, programming structures, or combinations thereof. In further various embodiments, the software modules comprise multiple files, multiple sections of code, multiple programming objects, multiple programming structures, or combinations thereof. In various embodiments, one or more software modules comprise, by way of non-limiting examples, web applications, mobile applications, and standalone applications. In some embodiments, the software modules are in one computer program or application. In other embodiments, the software modules are in two or more computer programs or applications. In some embodiments, the software modules are hosted on one machine. In other embodiments, the software modules are hosted on two or more machines. In further embodiments, the software modules are hosted on a cloud computing platform. In some embodiments, the software modules are hosted on one or more machines in one location. In other embodiments, the software modules are 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 the like. In light of the disclosure provided herein, one of skill in the art will recognize that many databases are suitable for storing and retrieving information. In various embodiments, suitable databases include, as non-limiting examples, relational databases, non-relational databases, object-oriented databases, object databases, entity-relationship model databases, associative databases, and XML databases. Further non-limiting examples 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] FIG. 20A shows a schematic diagram of a handheld OCT system with an eye adapter. In some cases, the system includes 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 includes one or more finger holders 2005. In some cases, the system further includes a measurement end with an adapter 2010 configured to interface with a user's eye socket. In some embodiments, the system further includes 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 includes a cap 2020. In some cases, the cap is utilized 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 placed over the measurement end of the system to protect the system components from damage.

[0221] In some cases, within the body, the system includes an optical system 104. 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 a light intensity meter 2035. In some cases, the light intensity meter performs continuous measurements of the emitted laser intensity, allowing 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 light intensity meter impinges on one or more beam splitters 510. In some cases, the one or more beam splitters 510 direct a portion of the light to the user's eye and another portion of the light to a reference mirror 530. In some cases, the reference mirror comprises a reference surface that is built into the body of the system. In some embodiments, the system further comprises 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 some cases, the battery is a lithium ion battery. In some embodiments, the battery is a nickel metal hydride battery. In some cases, the battery is a nickel cadmium battery. In some cases, the battery is operably coupled to a charging device 2040. In some cases, the charging device is a connected charging device. The charging device can be any connected charging device as known to those of skill in the art. In some cases, the charging device is an inductively coupled charging device. The charging device can be any inductively coupled charging device as known to those of skill in the art.

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

[0224] In some cases, the system includes additional components to allow the user to operate the system properly. In some embodiments, the system includes an orientation or motion sensor 2050. In some cases, the orientation or motion sensor includes a gyroscope to measure the orientation of the device and determine the eye being measured. In some cases, the orientation or motion sensor includes an accelerometer to measure the movement of the device. In some embodiments, the orientation or motion sensor includes any orientation or motion sensor as known to those skilled in the art. In some cases, the system includes a fixation target 2060 that is viewed when the miniature OCT system measures the retina. In some cases, the system includes a mechanical feature 2070 to provide electrical safety. In some embodiments, the system includes one or more status indicators 2080.

[0225] FIG. 20B illustrates a handheld OCT system adapted to measure the right or left eye. When operated to provide right eye measurements, the handheld OCT system 100 is operated in configuration 2020a with the eye cap 2020 positioned to the left of the measurement end of the handheld OCT system. When operated to provide left eye measurements, the handheld OCT system is operated in configuration 2020b with the eye cap positioned to the right of the measurement end of the handheld OCT system. When neither eye is being measured, the handheld OCT system is operated in configuration 2020c with the eye cap positioned to cover the measurement 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 is transitioned from configuration 2020a to configuration 2020b by a 180 degree rotation of the eye cap. In some cases, the handheld OCT system is equipped with a switch that detects the eye that is to be examined using the OCT system.

[0226] FIG. 20C illustrates 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 includes one or more visual indicators 2080. In some embodiments, the visual indicator includes a light source. In some cases, the light source is a light emitting diode (LED). In some cases, the visual indicator includes a first visual indicator 2082 to indicate whether the handheld OCT device is in operation. In some embodiments, the visual indicator includes a second visual indicator 2084 to indicate whether the handheld OCT device is utilizing battery power. In some cases, the visual indicator includes a third visual indicator 2086 to indicate whether the handheld OCT device is utilizing an external power source. In some cases, the visual indicator includes a fourth visual indicator 2088 to indicate whether the handheld OCT device is not suitable for use. In some embodiments, the end of the handheld OCT device opposite the measuring end includes an adapter 2040 for receiving power.

[0227] FIG. 20D shows a handheld OCT placed in close proximity to the eye to provide OCT measurements. In some cases, the measuring end of the handheld OCT system is shaped to conform to the eye socket. 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 obtain the OCT measurements.

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

[0229] 21 illustrates a calibration kit for a handheld OCT device. In some cases, the handheld OCT device 100 includes a calibration device 2100. In some embodiments, the calibration device is located on the inside surface of the cap 2020 of FIG.

[0230] 22 shows a schematic diagram of an optical system of a swept-source optical coherence tomography (SS-OCT) device utilizing a scanning mechanism, according to some embodiments. The optical system 102 comprises a light source 700, a first beam splitter 710, and a reference mirror 730 as described herein. A first processing unit 740 is coupled to a detector 742 to detect the swept-source interference signal. The first processing unit may comprise a first optical detector 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 include, for example, a collimating lens. The collimating optical element may collimate the light emitted from the light source prior to the light's interaction with other optical elements. The optical system may further include a lens 2220 that focuses the interference signal onto the photodetector 742. The optical system may further include a pinhole 2230 through which the 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 that reduces the intensity of the light incident on the reference mirror.

[0232] The optical system may further comprise a beam splitter 2250. The beam splitter may comprise 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 similar to the first processing unit 740, or other circuitry configured to control the amount of energy emitted by the VCSEL. The second processing unit may comprise a second photodetector (not shown) and a second signal processing unit (not shown), which may be similar 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 utilized to correct the SS-OCT signal detected by the first processing unit for errors associated with the variations in the intensity of the light emitted by the light source. The optical system may further comprise 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 may be configured in many ways. For example, the light source 700 may comprise a swept 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 range of the swept wavelength to about 20 nm or more. The VCSEL may also be coupled to an external mirror and an actuator to change the position of the mirror, for example, to increase the range of the swept wavelength. The VCSEL coupled to a movable mirror may be swept over a range of wavelengths in the range of about 10-30 nm or more.

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

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

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

[0237] 23A shows a scanning mechanism 2300 optically coupled to an eye with a miniature SS-OCT system, according to some embodiments. The scanning mechanism 2300 may comprise a first scanning optical element, such as a mirror 2310, and a telescope system comprising 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 scanned light beam towards the eye. The second telescope lens 2330 may comprise an aspheric lens.

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

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

[0240] 23B shows an array of retinal thickness (RT) or retinal layer thickness (RLT) measurement sites according to some embodiments. The scanning mechanism described herein can direct measurement light to multiple measurement locations 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. Although 25 measurement locations are depicted, the scanning mechanism may direct the measurement light to two or more measurement locations, five or more measurement locations, ten or more measurement locations, twenty or more measurement locations, fifty or more measurement locations, one hundred or more measurement locations, two hundred or more measurement locations, five hundred or more measurement locations, or one thousand or more measurement locations. RT or RLT measurements may be taken at each of the measurement locations to obtain multiple RT or RLT measurements. Multiple RT or RLT measurements may allow for 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 transverse to the first direction. The first distance may comprise a length 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 comprise a length 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] FIG. 24 shows a schematic diagram of the optical system of a compact swept-source optical coherence tomography (SS-OCT) device comprising a patient visualization system 2400. The patient visualization system 2400 may comprise a camera for viewing the fundus and a display for measuring the patient's visual acuity. The display for measuring the patient's visual acuity may be configured for the patient to gaze at a visual target, for example, by displaying a small object visible to the patient. The optical system 102 may comprise 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 including 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 the OCT measurement light to the eye and transmit visible light to the patient to display the image shown on the display to the subject and to image the fundus using a detector.

[0243] The visual function measurement device of the miniature SS-OCT system may include a Badal lens and an imaging system to compensate for the refraction of the patient. The lens 2450 may be coupled to an actuator to move the lens along the optical axis to focus an image of the fundus on the detector array and to focus the image on the display as viewed by the subject to correct the refractive error of the subject. The Badal lens may be configured to provide a virtual image viewed 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 measuring device presents one or more visual cues to the patient.

[0245] The miniature SS-OCT system may further comprise one or more camera devices, such as a fundus camera. The miniature SS-OCT system may comprise a visual camera device configured to measure, for example, an anterior portion of the eye. The optical system coupled to the fundus camera and the visual display may comprise a telescope comprising a first telescope lens 2440 and a second telescope lens 2450. The optical system may further comprise an aperture 2460 comprising a stop. The stop may comprise, for example, a ring stop. The optical system may further comprise a second beam splitter 2470. The second beam splitter may direct a portion of the light incident from the eye towards a detector array 2480 and a portion of the light incident from the microdisplay 2490 towards 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] The visual camera device may acquire images of the eye while the OCT system acquires RT or RLT measurements of the eye. The visual camera device may acquire images of the eye before, during, or after the OCT system acquires RT or RLT measurements of the eye as described herein. The fundus camera device may acquire images of the fundus while the OCT system acquires RT or RLT measurements of the eye. The fundus camera device may acquire images of the eye before, during, or after the OCT system acquires RT or RLT measurements of the eye. The images of the fundus acquired by the fundus camera device may undergo image processing to determine whether and how much the OCT measurement location has moved between two successive measurements (due to voluntary or involuntary movement of the eye or due to voluntary or involuntary movement of the handheld OCT system). The scanning of the OCT beam may be adjusted in response to eye movement to compensate for eye movement.

[0247] 25 illustrates a method 2500 for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to some 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 an estimated frequency, converting the estimated frequency to retinal thickness, processing information from multiple estimators, and processing multiple measurement points.

[0248] In step 2502, OCT data acquired by an OCT measurement system is read to form read data. In some cases, the read data comprises 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. The chirp correction may include resampling the OCT signal in the time domain. Resampling the OCT signal may convert a linear time signal into a linear wave vector signal. The resampling may compensate for phase instabilities that arise due to nonlinearities in the relationship between the wavelength of light emitted by the VCSEL or other light source and the drive current of the VCSEL or other light source, temperature variations, aging of optical components, vibration, or other environmental conditions. The resampling may be based on a phase measurement of the light source, such as a phase measurement method as described herein. The resampling may be performed during post-processing of the SS-OCT signal as described herein.

[0251] The resampling step may include a first and a second correction operation. In the first correction operation, the resampling step may correct an average nonlinearity of the phase of the light emitted by the VCSEL or other light source based on the average behavior of the 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 may be based on simultaneous acquisition of the phase signal and the SS-OCT signal, and may thus correct for 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, a frequency analysis is performed on the read data to obtain an estimated frequency. The frequency analysis may be performed using one or more estimators. The frequency may be performed using one, two, three, four, five, or more than five estimators. The estimator may utilize an eigenspace technique. The estimator may utilize an eigendecomposition technique. The estimator may utilize a Pisarenko decomposition technique. The estimator may utilize a multiple signal classification (MUSIC) technique. Each estimator of the one or more estimators may utilize the MUSIC technique with a unique filter. Each estimator may obtain an estimated frequency from the read OCT data.

[0253] In step 2510, one or more estimated frequencies are used to determine an estimated RT or RLT. The RT or RLT may be obtained from an analysis of terms of the interference signal. The terms used to determine the RT or RLT may comprise auto or cross terms of the interference signal, and combinations thereof. The auto terms may be generated by a back-reflected signal from a sample (e.g., a retina or a retinal layer) independent of a reference term of the SS-OCT system. The auto terms may correspond to a single frequency at a relatively low frequency. The frequency associated with the auto terms may be directly related to the RT or RLT. The RT or RLT may be obtained from an analysis of cross terms of the interference signal. The cross terms may be generated by a back-reflected signal from a sample and a reference mirror. The cross terms may correspond to a pair of frequencies at a relatively high frequency. The difference between the two frequencies of the pair of frequencies may be directly related to the RT or RLT. The terms may be combined to determine the thickness of the retina, the thickness of the layers, and the relative location of each of the layers of the retina.

[0254] Alternatively, or in combination, the 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 may be calculated by performing a mathematical transformation, such as a Hilbert transform, on the OCT signal. The envelope may be subjected to a filtering operation to obtain a filtered envelope. The RT or RLT may be related to the beat frequency of the filtered envelope. Estimation of the RT or RLT using the envelope of the OCT signal may be less susceptible to noise, such as that associated with motion (of the SS-OCT device or the user of the SS-OCT device).

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

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

[0257] 25 illustrates a method 2500 for extracting retinal thickness (RT) or retinal layer thickness (RLT) measurements from OCT measurements according to some embodiments, although one skilled in the art would recognize many variations and adaptations. For example, some of the steps may be omitted, some of the steps may be repeated, some of the steps may include sub-steps, steps may be performed in a different order, for example.

[0258] FIG. 26 shows a schematic diagram of an SS-OCT device incorporating a visual function measurement apparatus, according to some embodiments. The system may be sized for the patient to lift the system, e.g., may comprise sufficient weight to allow the patient to lift the system for measurement. The system may comprise a patient visualization system 2400, and the optical components may be arranged to provide a compact system that may be held by the patient during measurement, for example. The system may comprise a display 2490, and may comprise a fundus camera as described herein. Light from the light source 700 may be directed toward a mirror 710, which splits the light into a measurement section that is directed toward the eye 750 and a reference section that is directed toward a reference mirror 730. The reference mirror 730 may be coupled to an optical detector 2660, which may detect a portion of the light transmitted by the reference mirror. The optical detector 2660 may measure variations 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 to compensate for the varying distance from the patient to the subject's retina contacting structure. The reference section may comprise a mirror for deflecting the beam. The reference mirror may comprise multiple mirrors, such as mirror pair 2650. The location of mirror pair 2650 may be adjusted to adjust the optical path length of the reference section. For example, an actuator may be coupled to mirror pair 2650 to adjust the mirror 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 to the retina in a confocal configuration as described herein.

[0260] FIG. 34 shows a schematic diagram 3400 of the optical system of a SS-OCT device incorporating a fixation targeting device and a fundus imaging device, according to some embodiments.

[0261] The optical system may include a 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 the light along a reference arm of a reference mirror 730 to the beam splitter and a second portion of the light along a reference arm of the interferometer to the beam splitter as described herein. The second portion of the 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 the 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 comprise a mirror 2325 for deflecting the scanning light deflected by the scanning mirror towards the eye 750, as described herein. The scanning light may be reflected from the eye, the retina, or one or more layers of the retina and directed back 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 passed through a measurement arm of the interferometer and a reference light passed through a reference arm of the interferometer, as described herein.

[0262] The optical system may include a visual targeting pathway. The visual targeting pathway may include a visual targeting light source 3450. The visual targeting light source may include a light emitting diode (LED). The LED may emit light having a wavelength that is within the visible portion of the electromagnetic spectrum. For example, the LED may emit light having a wavelength that is within 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 that are within the visible portion of the electromagnetic spectrum. The visual targeting light source may direct light toward an opening 3455 that includes a stop. The stop may include, for example, a ring stop. The light may then pass to a diffuser 3460. The light may then pass to a collimating lens 2450 and stop 2460 as described herein. The light may be directed to a hot mirror 3435. The hot mirror may be configured to pass light from the visual target pathway to the lens 2440 as described herein. The light may then pass to the beam splitter 2470 as described herein. The beam splitter may pass the visual target light to the eye 750. The light may be detected by the eye and provide a target for the user to focus on. Focusing on the target may allow the user to reduce the user's eye movement during fundus, RT, or RLT measurements. In some cases, the beam splitter may pass the visual target light through the mirror 2325 and the second telescope 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 the detector 2480. The portion of the visual target light that is 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 that is within the near infrared portion of the electromagnetic spectrum. For example, the LED may emit light having a wavelength that is within the range of 700 nm to 2,500 nm. For example, the LED may emit light having a wavelength of about 780 nm. The LED may emit light at multiple wavelengths that are within the near infrared portion of the electromagnetic spectrum. The fundus illumination light source may direct light toward an aperture 3415 that includes a stop. The stop may include, for example, a ring stop. 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. The first polarizer may impart s-polarized light to the light. The first polarizer may be a p-polarizer. The first polarizer may impart p-polarized light to the light. The light may then pass to a beam splitter 2470 as described herein. The beam splitter may pass the fundus illumination light to the eye 750. In some cases, the beam splitter may pass the fundus illumination light through a mirror 2325 and a second telescope lens 2330 as described herein to the eye. 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 that is 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 pass light having a polarization similar to that imparted by the first polarizer. 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 fundus of the user's eye. The imaging lens and camera may be configured to record a series of images of the fundus of the user's eye. 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 the image of the fundus to a template. The template may comprise a small region of the image of the eye that contains a vein. The image processor may be configured to detect tubular structures of the diameter of the vein. For example, the image processor may be configured to implement a filter, such as a Hessian multi-scale filter, to detect the vein. The filter may enhance the definition of the region of the fundus image that contains a vein and the definition of the region of the template that contains a vein. The image processor may cross-correlate the enhanced region of the fundus image with the enhanced region of the template. In this manner, the location of the vein may be determined. The location of the vein may be determined for each fundus image in the series of fundus images. In this manner, the relative movement of the eye may be measured over time.

[0266] FIG. 35 shows a schematic diagram 3500 of an electronic circuit for controlling the optical system of the compact SS-OCT system described herein. The optical system described herein can 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 can be electronically coupled to a first filter 3510, such as a low pass filter. The first filter can be configured to receive an 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 can include a data acquisition card, such as a data acquisition card provided by National Instruments. The data acquisition module can include one or more analog-to-digital converters (ADCs) or one or more digital-to-analog converters (DACs). The data collection module may be configured to sample the ADC at a sampling rate of at least 1 kilosample per second (kS / s), at least 2 kS / s, at least 5 kS / s, at least 10 kS / s, at least 20 kS / s, at least 50 kS / s, at least 100 kS / s, at least 200 kS / s, at least 500 kS / s, at least 1,000 kS / s, at least 2,000 kS / s, at least 5,000 kS / s, or at least 10,000 kS / s. The data collection module may be configured to sample the ADC at a sampling rate that is within a range defined by any two of the foregoing values. The data collection module may be configured to sample the DAC at a sampling rate of at least 1 kilosample per second, at least 2 kS / s, at least 5 kS / s, at least 10 kS / s, at least 20 kS / s, at least 50 kS / s, at least 100 kS / s, at least 200 kS / s, at least 500 kS / s, at least 1,000 kS / s, at least 2,000 kS / s, at least 5,000 kS / s, or at least 10,000 kS / s. The data collection module may be configured to sample the DAC at a sampling rate that is within a range defined by any two of the foregoing values.

[0267] The interferometer apparatus for enhancing phase stability 3640 described herein (e.g., with respect to FIG. 36) 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 apparatus 3640, filter the phase measurements, and pass the filtered phase measurements to a data collection 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 collection module. The first safety circuit may be configured to receive a first status signal from the data collection 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 send 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 subject's eye to a safe level. In the case where the first safety device is activated, the first safety circuit may send a status signal to the data collection module. This status signal may be passed to an 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 collection module. The second safety circuit may be configured to receive a second status signal from the data collection module. The second safety circuit may be configured to monitor a signal 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 send a signal to disable the light source driver or otherwise reduce the power provided by the light source driver. Disabling or reducing the power from the light source driver may reduce the amount of light intensity provided by the light source to a safe level. The data collection module 3580 may be configured to send a modulation signal to the light source driver to modulate the operating current of the light source as described herein.

[0270] The data collection module 3580 may be electronically coupled to the fundus camera 2490 described herein. The data collection module may be configured to trigger measurements from the fundus camera. A signal from the fundus camera may be directed to the calculation module 3585. The calculation module may comprise an external computer. The calculation module may comprise a personal computer or a workstation. The calculation module may comprise a mobile device such as a tablet or a 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 a 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 computation module may be electronically coupled to a control bus module 3590. The control bus module may comprise a universal serial bus (USB) hub. The computation module may route signals to the control bus module 3590 to control the operation of one or more optical components of the compact SS-OCT system. For example, the control bus module may route signals to a scanner interface module 3560 that controls the operation of the scanning element 2310 described herein. The scanner interface module may comprise a high voltage driver that powers the scanning element at a high voltage, such as a voltage of up to 200V. The control bus module may route signals to a first OCT focusing element, such as any 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 route signals to a second OCT focusing element, such as any 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. The control bus module may direct a signal 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 side view of the eye. The images collected by the live view camera may assist an operator of the SS-OCT device described herein in properly aligning the device with the subject's eye. For example, the images collected by the live view camera may enable an 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 compact 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] 36 shows a schematic diagram 3600 of the optical system of a SS-OCT device incorporating an interferometer to enhance phase stability. The optical system may include 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 detector 740 may be arranged to generate an OCT signal from an eye 750 as described herein.

[0274] The optical system may include an aperture 2460 with a stop. The stop may include, for example, a ring stop. The stop 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 sufficient numerical aperture to direct collimated light emitted by the light source into an optical fiber. The first coupling lens may be configured to direct the light to the interferometer arrangement 3640.

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

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

[0277] The second coupling lens may be a fiber coupling lens. The second coupling lens may have a sufficient numerical aperture to accept the light emitted by the interferometer device 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 by the SS-OCT system on the retina.

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

[0279] FIG. 27A shows a dark visual cue on a light background. The visual cue may be presented alone or in combination. The visual cue may comprise a letter in an orientation, such as a rotating E. The subject may input the orientation of the letter to determine the subject's visual acuity. The visual cue may comprise multiple dark letters 2710a, 2710b, 2710c, and 2710d, such as the letter "E" on a light background 2700. Although four letters are shown, the visual cue may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 letters. The letters may move along the background, such as downward along the background. Other visual stimuli, such as arrows, may be presented, with the patient indicating the orientation of the letters.

[0280] 27B shows a dark visual cue on a dark background. The visual cue may comprise 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 comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 letters. The letters may move along the background, such as downward along the background. The letters may be presented in different orientations, such as facing left, right, up, or down.

[0281] In many embodiments, the visual cue is shown on a display as described herein, and the lens can compensate for the subject's refractive error to test the subject's vision. The compact SS-OCT system can include an input for the patient to input the orientation of the characters presented so that the patient's vision can be determined. The input can include, for example, an input configured to receive the orientation of the characters, such as a button or multiple buttons.

[0282] FIG. 28A shows a schematic diagram of a housing for an exemplary handheld monocular OCT system, according to some embodiments. The left side of the figure shows a side view 2800 of the housing. The housing may include a body 2810. The body of the housing may include a handle 2850 for a patient to grip the system. The body 2810 may be coupled to an ocular 2805 or a structure for contacting the patient, such as foam or other structure. The housing may have an interior volume that contains any of the components of the handheld OCT systems and devices described herein. The reference section of the interferometer may extend at least partially into the handle 2850, for example.

[0283] The eyepiece 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 a subject'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 subject's eye, and an opening 2830 configured to allow OCT measurement light to travel from the OCT system to the eye and back. The opening may be further configured to present visual cues to the subject (such as one or more of the letter "E") as described herein. The housing may comprise a mechanism 2835 that allows the subject to indicate an orientation of each letter presented to them (such as looking left, right, up, or down).

[0285] FIG. 28B shows a housing for an exemplary handheld monocular OCT system, according to some embodiments.

[0286] 29A and 29B show a configuration of a handheld binocular OCT system, according to some embodiments. Alternatively, the system may comprise a monocular system, where the eye not being measured is occluded with the measurement system. The left side of the figure shows a side view 2900 of the housing. The housing may comprise ocular lenses 2905a and 2905b and a body 2910. The housing may have an interior volume that contains any of the components of the handheld OCT systems and devices described herein. The ocular lenses 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 both hands of the subject.

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

[0288] FIG. 29C illustrates an exemplary handheld binocular OCT system configuration, according to some embodiments.

[0289] FIG. 30 shows a configuration of an exemplary handheld binocular OCT system, according to some embodiments. The housing 3000 may include ocular lenses 3005a and 3005b and a body 3020. The housing may have an interior volume that includes any of the components of the handheld OCT systems and devices described herein. The ocular lenses 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 both hands of the subject. One of the ocular lenses may include an opening 3010 configured to allow the OCT measurement light to travel from the OCT system to one of the eyes and back. The opening may further be configured to present a visual cue to the subject, such as one or more of the letter "E", as described herein. The housing may include a mechanism 3015 that allows the subject to indicate an orientation of each letter presented to them, such as looking left, right, up, or down. The body of the housing may include a cutout area. The orientation of the cutout area may indicate the eye being measured using the OCT system. The cutout area may be located on the opposite side of the housing from the eye being measured.

[0290] An orientation sensor, such as an accelerometer, may be mechanically coupled to the optical system and electronically coupled to the control unit, as described herein, to measure the eye measured in response to the orientation of the orientation sensor.

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

[0292] FIG. 31B shows a housing for an exemplary handheld binocular OCT system oriented to measure the right eye of a subject.

[0293] FIG. 32A illustrates a VCSEL coupled to a cooler to increase the range of wavelengths swept with the VCSEL, according to some embodiments. The VCSEL of the SS-OCT system described herein may be subjected to a cooling procedure to reduce the operating temperature of the VCSEL to a temperature below the ambient temperature of about 37° C. to increase the range of wavelengths swept by the VCSEL. The cooling can be combined with overdriving of the VCSEL as described herein to further increase the range of wavelengths swept by the VCSEL. The VCSEL of the SS-OCT system may be cooled 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 of the SS-OCT system may be cooled by an amount within a range defined by any two of the aforementioned values, for example, by an amount within a range of 20° C. to 70° C. The range of wavelengths swept may be increased by 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or by an amount within a 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 and cooled to increase the sweep range by about 2 nm, providing a total 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 with a gas such as nitrogen that expands to cool the VCSEL, or a cooled circulating fluid, and combinations thereof. The cooler may include, for example, a heat sink coupled to the VCSEL.

[0294] FIG. 32B shows a schematic diagram 3200 of a VCSEL coupled to a thermoelectric cooler. The VCSEL 700 may be mounted to a VCSEL driver 3210. The VCSEL driver may comprise a printed circuit board (PCB). The VCSEL may be mounted to 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 heat sink 3220 configured to draw 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 by 10° C., 20° C., 30° C., 40° C., 50° C., 70° C., 80° C., 90° C., or more. The TEC may be configured to cool the VCSEL by an amount within a 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. The temperature sensor may be configured to measure an operating temperature of the VCSEL. The temperature sensor and the TEC may be coupled to a TEC controller 3250. The TEC controller may control the cooling power of the TEC based on the measured temperature of the VCSEL by the temperature sensor. In this manner, the TEC, thermistor, and TEC controller may form a negative feedback system designed to maintain the VCSEL at a stable operating temperature, such as those described herein.

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

[0296] The miniature SS-OCT system may be mounted on a support system 3300, e.g., releasably mounted or attached to a support. The miniature SS-OCT system may be fixedly attached to the support system. The miniature SS-OCT system may be removably attached to the support system. The support system may be mounted to a tabletop or other surface. The support system 3300 may comprise a base 3310. The base may be attached to or placed on a tabletop or other surface. The base may be fixedly attached to a tabletop or other surface. The base may be removably attached to a tabletop or other surface.

[0297] The support system may further comprise a mounting surface 3320 for receiving the 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 may be mounted. The mounting surface may be coupled to the base by a first coupler 3330. The first coupler may be configured to allow a user to vary the distance between the mounting surface and the base, as shown by the arrow labeled "1" in FIG. 33A. The distance between the mounting surface and the base may be adjustable by 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 by a value that is within a range defined by any two of the aforementioned values. The distance between the mounting surface and the base may be adjusted to increase the comfort of the user while using the miniature SS-OCT system.

[0298] The support system may include a second coupler configured to allow a user to vary the angle between the mounting surface and the base, as shown by the arrow labeled "2" in FIG. 33A. The angle between the mounting surface and the base may be adjustable by 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 by a value that is within a range defined by any two of the aforementioned values. The angle between the mounting surface and the base may be adjusted to increase the user's 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 a 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 coupler configured to allow a user to vary the distance between the chin rest and the eyepiece, as shown by the arrow labeled "3" in FIG. 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 that is within a range defined by any two of the aforementioned values. The distance between the chin rest and the mounting surface may be adjusted to increase the comfort of the user 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 and the eyepiece and mounting surface can be adjusted to align the user's eye with the optical axis of the miniature SS-OCT system.

[0300] The compact SS-OCT system mounted on the support may have a length, a width, and a height. The length may comprise the longest dimension across the system, the width may comprise the next longest dimension across the system, and the width may comprise the shortest dimension across the system. The length, width, and height may extend across one another, for example perpendicular to one another. The compact SS-OCT system may have a length of 10 cm, 20 cm, or 50 cm. The compact SS-OCT system may have a length that is within a range defined by any two of the aforementioned values. The compact SS-OCT system may have a width of 5 cm, 10 cm, or 25 cm. The compact SS-OCT system may have a width that is within a range defined by any two of the aforementioned values. The compact SS-OCT system may have a height of 2.5 cm, 5 cm, or 10 cm. The compact SS-OCT system may have a height that is within a range defined by any two of the aforementioned values.

[0301] The miniature 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 that is within a range defined by any two of the aforementioned values.

[0302] FIG. 33B shows a user using a tabletop mounted SS-OCT device. EXAMPLES

[0303] Example 1: Limit of detection for RT or RLT measurements Figure 14 shows the optical setup for determining the limit of detection for measuring changes in RT or RLT using a SS-OCT system utilizing a single VCSEL and no reference arm. The setup includes a VCSEL (V), a photodetector (P), a collimating lens (L1), a beam splitter (BS), a lens (L2) for focusing light onto the photodetector, a lens (L3) for focusing light onto the sample, a 22 mm long cylinder made of polymethylmethacrylate (PMMA), a refractive index matching oil with a refractive index of 1.5120, two 150 μm thick glass coverslips with an adjustable air 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 turning a microscrew with a resolution of 25 μm per turn. The SS-OCT signal is generated by the interference between light reflected from a first glass-air interface and a second glass-air interface.

[0304] Example 2: Performance of a VCSEL driven outside its rated operating range FIG. 15 shows the oscilloscope signal at two different times of a VCSEL driven outside its rated operating range. The VCSEL had a center wavelength of about 850 nm and a rated range of emission wavelengths of about 1.8 nm. The VCSEL current was swept continuously 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 sweep of about 7.25 hours each. Between each interval, the VCSEL was shut down 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 varied little between the first measurement at 0 hours of operation and subsequent measurements after the VCSEL had been in operation for 29 hours. Thus, 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 compares favorably with the usage requirements of VCSELs implemented in handheld SS-OCT devices. Assuming the device is used twice a day for 5 years, for 20 seconds per measurement, the VCSEL would accumulate approximately 20 hours of active use. Thus, a handheld SS-OCT device based on a VCSEL driven outside its rated operating range may continue to produce useful results throughout its intended operating life.

[0305] Example 3: OCT signal for varying thickness FIG. 16 shows oscilloscope signals for two different configurations of the optical setup of FIG. 14. The VCSEL had a central wavelength of about 850 nm and a nominal range of emission wavelengths of about 1.8 nm. The VCSEL current was swept continuously 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 the interference signal (purple) were recorded using an oscilloscope. Two glass cover slides with a thickness of 150 μm were placed an arbitrary distance apart, referred to as the zero position. The zero position was chosen such that 2-3 periods were recorded from the interference signal due to the light reflecting from the first glass cover slide and the light reflecting from the second glass cover slide. The change in the distance between the two glass cover slips resulted in a change in the frequency of oscillation of the interference signal. For example, at the zero position, the interference signal fluctuated with a frequency of about 950 Hz. After adding a 25.0 μm displacement from the zero position to the distance between the two coverslips, the interference signal fluctuated with a frequency of approximately 1,050 Hz.

[0306] (Example 4) Extraction of frequency from interference signal FIG. 17 shows a method of signal processing to extract the frequency of oscillation of an interference signal generated using an SS-OCT system utilizing a single VCSEL and no reference arm. The interference signal recorded on an oscilloscope is corrected by dividing the interference signal by the VCSEL light intensity. This produces a slowly decaying sine wave. The corrected data is then fitted to a sine wave using a nonlinear least squares fitting procedure. The frequency of oscillation of the corrected interference signal is extracted from the nonlinear least squares fit.

[0307] Example 5: Repeatability measurements FIG. 18 shows the results of a study to determine the repeatability of extracting the frequency of oscillation of an interference signal generated using an SS-OCT system utilizing a single VCSEL and no reference arm. The distance between the two glass coverslips was varied in increments of 12.5 μm. The frequency of a sinusoidal fit was obtained from the interference signal at each value of the distance between the two glass coverslips. The experiment was replicated 5-10 times for each value of the distance between the two glass coverslips.

[0308] FIG. 19 shows the mean and 95% confidence interval of frequencies obtained during a study to determine the repeatability of extracting the frequency of oscillation of an interference signal generated using a SS-OCT system utilizing a single VCSEL and no reference arm. With the exception of the 25 μm and 37.5 μm data points, each of the examined distances is separated from other examined distances by more than two standard deviations from distances 12.5 μm below itself and 12.5 μm above itself. For all data points, each of the examined distances is separated from other examined distances by more than two standard deviations from distances 25.0 μm below itself and 25.0 μm above itself. Thus, it can be inferred that the present method for determining changes in layer thickness (here, the gap between two glass cover slips) has a limit of detection of changes in layer thickness that is between 12.5 μm and 25.0 μm. This compares favorably to the operational requirements of a handheld SS-OCT system for measuring changes in RT.

[0309] (Example 6) Fundus Imaging 37A-C show exemplary fundus images obtained using the system and method described herein. FIG. 37A shows a fundus image with relatively high contrast and a relatively high amount of observable structures. FIG. 37B shows a fundus image with relatively low contrast and a relatively low amount of observable structures. FIG. 37C shows a corrected fundus image subjected to the fundus recognition method described herein. The fundus image in FIG. 37C was obtained by applying the fundus recognition method described herein to the image in FIG. 37B (fundus image with relatively low contrast and a relatively low amount of observable structures). As shown in FIG. 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 in the fundus image even when the fundus image is of relatively low quality. The substructures of the fundus can be used for image registration.

[0310] (Example 7) Resampling for chirp correction 38A-38B show the effect of resampling for chirp correction of SS-OCT signals in the time domain. FIG. 38A shows the effect of resampling for chirp correction of SS-OCT signals having a relatively low frequency. FIG. 38B shows the effect of resampling for chirp correction of SS-OCT signals having a relatively high frequency. The results of the resampling procedure are shown in the frequency domain in FIG. 39A-C.

[0311] Example 8. Frequency drift of uncorrected and chirp-corrected SS-OCT signals 39A-C show the frequency drift of uncorrected and chirp-corrected SS-OCT signals in the frequency domain. FIG. 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 experiences a drift of more than 50 kHz over a period of about 2 seconds. FIG. 39B shows the frequency drift of an SS-OCT signal that has undergone pre-sampling for chirp correction. The signal shows a significantly smaller frequency drift, varying by a few Hz over a period of about 2 seconds. FIG. 39C shows the frequency drift of an SS-OCT signal that has undergone final resampling for chirp correction. The signal shows an even smaller frequency drift, varying by a small amount over a period of about 1.6 seconds. Thus, the frequency drift can be corrected using the chirp correction or resampling method as described herein. The reduction in frequency drift using the resampling methods described herein results in a narrower measured frequency distribution, yielding a more precise RT or RLT measurement with a higher signal-to-noise ratio.

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

[0313] Example 10: Correction of phase shift associated with patient movement 41A-D show simulations of phase shifts associated with patient movement. FIG. 41A shows a simulated signal that has undergone a phase shift of π radians over the duration of half the signal's length. FIG. 41A shows the frequency spectrum of a simulated signal that has undergone a phase shift of π radians over the duration of half the signal's length. A phase shift of π radians corresponds to a patient movement of about 225 nm for light having a wavelength of 850 nm. The phase shift imparts significant errors in the frequency spectrum. FIG. 41C shows a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of the signal. FIG. 41D shows the frequency spectrum of a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of the signal. Although present for only a short amount of time, the phase shifts still impart significant errors in the frequency spectrum. These phase shifts can be corrected by utilizing fast A-scan or chirp correction methods as described herein.

[0314] 42A-D show a simulation of the effect of A-scan time on the error resulting from a phase shift associated with patient motion. FIG. 42A shows a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of a signal with an A-scan duration of 2 ms. FIG. 42B shows a frequency spectrum of a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of a signal with an A-scan duration of 2 ms. The phase shift imparts a significant error in the frequency spectrum over this relatively long A-scan duration. FIG. 42C shows a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of a signal with an A-scan duration of 0.4 ms. FIG. 42D shows a frequency spectrum of a simulated signal that has undergone a phase shift of π radians over the duration of a single cycle of a signal with an A-scan duration of 0.4 ms. The phase shift imparts a significantly smaller error in the frequency spectrum over this relatively short A-scan duration. Thus, noise associated with patient motion can be reduced by utilizing a fast A-scan as described herein.

[0315] Example 11. Measurement of typical patient movement 43A-B show the amplitude of typical patient movement. FIG. 43A shows the movement along the optical axis of a patient who keeps himself stationary as much as possible. The large jump between positions occurs due to the patient blinking. Ignoring blinks, typical patient movement has an amplitude of about 0.25 mm and a duration of about 1.2 seconds for a typical movement speed of 210 nm / ms. Such a movement speed can be corrected by using the fast A-scan described herein. The maximum patient movement has an amplitude of about 0.25 mm and a duration of about 0.16 seconds for a maximum movement speed of 1,560 nm / ms. FIG. 43B shows the movement along the optical axis of a patient who is intentionally moving. Ignoring blinks, typical intentional patient movement has an amplitude of about 2.19 mm and a duration of about 0.76 seconds for a typical movement speed of 2,900 nm / ms.

[0316] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present invention be limited by the specific examples provided herein. Although the present invention has been described with reference to the foregoing specification, the description and illustration of the embodiments herein are not intended to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to 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 depictions, configurations, or relative proportions set forth herein, which depend upon a variety of 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. It is therefore contemplated that the present invention shall cover any such alternatives, modifications, variations, or equivalents. The following claims define the scope of the present invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

[Claim 1] The invention described in this specification.

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