JP2016510628A - Portable retinal imaging device - Google Patents

Abstract

A portable MEMS-based scanning laser ophthalmoscope (MSLO). In one example, the MSLO is a two-dimensional laser irradiation subassembly that generates a laser irradiation beam and a two-dimensional configuration configured to receive the laser irradiation beam and scan at least a portion of the retina of the eyeball to be imaged with the laser irradiation beam. A MEMS scanning mirror, an optical system configured to irradiate the retina by directing a laser irradiation beam from the scanning mirror to the eyeball, and a configuration for generating an image of the retina by blocking the optical radiation reflected from the eyeball Detector subassembly. The optical system includes a polarizing beam splitter positioned between the scanning mirror and the eyeball and configured to direct the laser illumination beam to the eyeball and to direct the optical radiation reflected from the eyeball to the detector subassembly. Including.

Description

Background Fundus cameras have been used by ophthalmologists for many years to image the inner surface of the eyeball (retina), including the fundus, optic disc, sunspot and fovea, and posterior pole. In general, a fundus camera has a spherical field of view of approximately 30-45 degrees on the retina. These cameras operate on the principle of direct or indirect optometry, illuminate the eye with light from a flash bulb, and capture two-dimensional images with imaging optics and detectors. The light from the flash bulb is focused through a series of lenses through a donut-shaped aperture, then through a central aperture and in an annular shape before passing through the camera objective and the cornea on the retina. Form. Light reflected from the retina passes through a donut-shaped unilluminated hole formed by the illumination system and into the telescopic eyepiece. In order to acquire an image of the retina, the mirror intercepts the path of the illumination system and allows the light from the flash bulb to pass through the eyeball. At the same time, the mirror falls in front of the observation telescope and changes the direction of the light to the detector. These instruments are complex in design and difficult to manufacture to clinical standards. Moreover, the fundus camera is limited to a relatively small field of view due to aberrations caused by the imaging optics common to both the illumination and imaging paths and the front objective lens, and more than diffraction limited resolution on the retina. Inferior. Portable or handheld fundus cameras are commercially available but are not widely used. This is because a skilled photographer is required for the operation, and the captured image is inferior to the desktop apparatus.

  Another device used to acquire images of the retina is a scanning laser ophthalmoscope that can image the retina with a better spatial resolution than a fundus camera. A scanning laser ophthalmoscope uses a laser irradiator that is raster scanned over the retina and a detector that is configured to measure the light reflected from the retina at each point of the scan. The scanning elements used to scan the illuminator include a rotating polygon, a scanning prism, and a galvanometer driven movable mirror. Because these elements are difficult to align and are vulnerable to shock and vibration, it is impractical to use them in portable systems.

  For wide field of view (FOV) imaging, existing systems use elliptical mirrors for virtual point scanning in the retina. The actual scan point is located on one focus of the ellipse and the other focus of the ellipse is located at the pupil of the human eyeball. If the scan is symmetrical about the minor axis of the ellipse, the virtual scan angle is equal to the actual scan angle.

SUMMARY OF THE INVENTION Aspects and embodiments are directed to a portable device for acquiring images of the retina. In particular, aspects and embodiments replace a conventional scanning element with a two-dimensional MEMS (microelectromechanical system) scanning mirror, thereby enabling a steady scan in a portable device as described further below. Directed to the ophthalmoscope. According to an embodiment, the apparatus comprises a multicolor light source having a polarization control unit for providing incident polarized illumination, a two-dimensional MEMS scanning mirror, and an optical imaging system for directing illumination across the retina surface. including. As will be described in more detail below, the scanning mirror directs incident illumination received along the optical axis and transmitted through the imaging system towards the retina of the eyeball. The polarizing beam splitter is used to direct image bearing light reflected from the retina onto the confocal focusing optics and detector, thereby acquiring an image of the retina.

  According to one embodiment, a MEMS-based scanning laser ophthalmoscope is provided on a laser irradiation subassembly configured to generate a laser irradiation beam and on at least a portion of the retina of an eyeball that receives the laser irradiation beam and is to be imaged. A two-dimensional MEMS scanning mirror configured to scan a laser beam with a laser irradiation beam, and optically coupled to the MEMS scanning mirror, and configured to irradiate the retina of the eyeball by directing the laser irradiation beam from the scanning mirror to the eyeball And a detector subassembly configured to generate an image of the retina that is optically coupled to the optical system and blocks optical radiation reflected from the eyeball. The optical system includes a polarizing beam splitter positioned between the scanning mirror and the eyeball and configured to direct the laser illumination beam to the eyeball and to direct the optical radiation reflected from the eyeball to the detector subassembly. Including.

  In one example, the two-dimensional MEMS scanning mirror is configured to scan a portion of the retina with a laser illumination beam in a Lissajous pattern. In one example, the polarizing beam splitter is configured to transmit a laser illumination beam to the eyeball and reflect optical radiation reflected from the eyeball to the detector subassembly. In another example, the polarizing beam splitter is configured to reflect the laser illumination beam to the eyeball and transmit the optical radiation reflected from the eyeball to the detector subassembly. The optical system may further include an on-axis objective lens positioned between the polarizing beam splitter and the eyeball. The detector subassembly may include a photodetector such as an avalanche photodiode, a charge coupled device, or a photomultiplier tube. In one example, the detector subassembly further includes focusing optics configured to focus the optical radiation onto the photodetector. The detector subassembly may further include a confocal aperture optically coupled between the focusing optic and the photodetector. In another example, the laser illumination subassembly includes at least one of a near infrared laser light source and a visible laser light source.

  A MEMS-based scanning laser ophthalmoscope includes a display screen optically coupled to an optical system, a controller configured to control a laser irradiation subassembly to display a fixation target on the display screen, and laser irradiation. A dichroic beam splitter configured to optically couple the display screen to an irradiation path along which the beam travels to the eyeball. The illumination path includes a polarizing beam splitter that is configured to direct light intensity corresponding to the fixation target to the eye to allow the eye to view the fixation target. In one example, the controller is further configured to guide the eyeball orientation by adjusting the display location of the fixation target on the display screen to obtain an image of a selected region of the retina. The MEMS-based scanning laser ophthalmoscope is configured to couple an illuminator configured to provide an alignment beam, a camera configured to detect the alignment beam reflected from the eyeball, and the alignment beam into the irradiation path. And an alignment and focusing subsystem that includes a configured beam splitter. In another example, the MEMS-based scanning laser ophthalmoscope further comprises an electrically adjustable lens positioned in the illumination path between the laser illumination subassembly and the scanning mirror, and the controller includes a camera and an electrically adjustable And is further configured to adjust the focus of the electrically adjustable lens based on information obtained from the alignment beam coupled to the possible lens, reflected from the eyeball and detected by the camera.

  According to another embodiment, a method for imaging a retina of an eyeball by a scanning laser ophthalmoscope includes generating a laser irradiation beam, directing the laser irradiation beam to the eyeball by a polarizing beam splitter, and two-dimensional MEMS. Using a scanning mirror to scan with a laser irradiation beam around the scanning point of the eyeball, to generate a two-dimensional irradiation area that irradiates the retina of the eyeball, and to reflect from the eyeball without descanning the optical radiation Directing the emitted optical radiation to a detector subassembly by a polarizing beam splitter and generating an image of the retina from the optical radiation.

  In one example, generating the laser irradiation beam includes generating at least one of a near infrared irradiation beam and a visible irradiation beam. In another example, scanning with a laser irradiation beam includes scanning the laser irradiation beam with a Lissajous pattern. In one example, the polarizing beam splitter is positioned between the scanning mirror and the eyeball, and directing the laser illumination beam to the eyeball includes transmitting the laser illumination beam through the polarization beam splitter, and optical reflected from the eyeball. Directing radiation to the detector subassembly includes reflecting the optical radiation by a polarizing beam splitter. In another example, the polarizing beam splitter is positioned between the scanning mirror and the eyeball, and directing the laser illumination beam to the eyeball includes reflecting the laser illumination beam by the polarization beam splitter and reflected from the eyeball. Directing the optical radiation to the detector subassembly includes transmitting the optical radiation through a polarizing beam splitter. The method includes irradiating an eye with an alignment beam, detecting the alignment beam, and an electrically adjustable lens positioned between a laser irradiation subassembly that generates the laser irradiation beam and a scanning mirror. Adjusting the focus may further include focusing the laser irradiation beam onto the retina of the eyeball. In one example, the method displays the fixation target on the display screen and adjusts the display location of the fixation target on the display screen so as to obtain an image of a selected region of the retina. And further guiding the orientation.

  Further aspects, embodiments, and advantages of these exemplary aspects and embodiments are described in detail below. Any embodiment disclosed herein may be combined with any other embodiment in any manner consistent with at least one of the principles disclosed herein. References to “forms”, “some embodiments”, “alternative embodiments”, “various embodiments”, “one embodiment”, etc. are not necessarily mutually exclusive and are described with respect to the embodiments. It is intended to indicate that a particular feature, structure, or characteristic may be included in at least one embodiment. The appearances of such terms herein are not necessarily all referring to the same embodiment.

BRIEF DESCRIPTION OF THE DRAWINGS Various aspects of at least one embodiment are described below with reference to the accompanying drawings. The figures are not intended to be drawn to scale. The figures are included to provide illustration and further understanding of various aspects and embodiments, and are incorporated in and constitute a part of this specification, but are not intended as a definition of the scope of the invention. In the figures, each identical or nearly identical component that is illustrated in various figures is represented by a like numeral. For purposes of clarity, not all components are labeled in all drawings.

It is a functional block diagram of an example of a MEMS base scanning laser ophthalmoscope according to an aspect of the invention. 1 is a block diagram of an example of a portable MEMS-based scanning laser ophthalmoscope within a housing, according to aspects of the invention. FIG. It is the schematic which illustrates the example of the conventional confocal scanning laser ophthalmoscope. 1 is a schematic diagram illustrating an example of a transmission architecture for a MEMS-based scanning laser ophthalmoscope according to aspects of the invention. FIG. 1 is a schematic diagram illustrating an example of a reflective architecture for a MEMS-based scanning laser ophthalmoscope according to aspects of the invention. FIG. 2 is a functional block diagram of an example of a laser irradiation subassembly according to an aspect of the invention. FIG. 1 is a schematic diagram of an example structure of a MEMS-based scanning laser ophthalmoscope having a transmission architecture according to aspects of the invention. FIG. 1 is a schematic diagram of an example structure of a MEMS-based scanning laser ophthalmoscope having a reflective architecture according to aspects of the invention. FIG. It is the schematic of another structural example of the MEMS base scanning laser ophthalmoscope which concerns on the situation of invention. It is the schematic of another structural example of the MEMS base scanning laser ophthalmoscope which concerns on the situation of invention. It is the schematic of another structural example of the MEMS base scanning laser ophthalmoscope which concerns on the situation of invention. It is the schematic of another structural example of the MEMS base scanning laser ophthalmoscope which concerns on the situation of invention. 3 is a flowchart of an example of a retinal imaging process according to an aspect of the invention. 3 is a flowchart of an example of a retinal imaging process according to an aspect of the invention. 3 is a flowchart of an example of a retinal imaging process according to an aspect of the invention. 4 is an example of a display screen image presented to a patient using an embodiment of a MEMS-based scanning laser ophthalmoscope according to aspects of the invention. 1 is a schematic diagram of a structural example of a MEMS-based scanning laser ophthalmoscope configured to provide binocular fixation according to an aspect of the invention. FIG. 6 is a schematic diagram of another example structure of a MEMS-based scanning laser ophthalmoscope configured to provide binocular fixation according to an aspect of the invention.

DETAILED DESCRIPTION Aspects and embodiments are directed to a small, wide-field scanning laser ophthalmoscope that is configured to allow handheld, portable retinal imaging, for example in remote locations and home clinics. Portable retinal imaging is used to screen distant residents for eye diseases and to screen combatants for eye damage on the battlefield to observe the direct visual impact of trauma on the battlefield. Would be very valuable. Similarly, retinal imaging in the clinic will greatly improve the efficiency of screening diabetic patients for retinopathy, for example. Conventional tabletop retinal imaging devices are too large for such applications and / or require operation by trained professionals.

  According to one embodiment, self-managing wide-field imaging of the retina with a small and portable hardware ground area is achieved by a MEMS-based scanning laser ophthalmoscope (MSLO). To enable steady scanning on portable devices, two-dimensional (2D) MEMS scanning mirrors replace conventional scanning elements such as the rotating polygons, scanning prisms, and galvanometer driven movable mirrors described above. According to one embodiment, for a low cost design, the off-axis conical mirror front objective lens previously used in scanning laser ophthalmoscopes is replaced with an on-axis refractive objective lens, thereby condensing path And the aberrations that must be corrected in the illumination path. As described in more detail below, a polarizing beam splitter may be used to reduce ghost reflections caused by the use of refractive elements in a common illumination and detection / collection path. This makes it possible to provide a confocal scanning laser ophthalmoscope whose defocusing path is not descanned, as will be described further below. In addition, as described further below, embodiments of the MSLO present a fixation target to a human subject with real-time feedback to enable fully automated, self-managed retinal imaging. Configured.

  Embodiments of MSLO include, for example, screening for diabetic retinopathy using a telemedicine network, imaging military eye damage on the battlefield, retinal imaging in locations where global medical services are inadequate, and mobile It may enable retinal imaging outside conventional ophthalmic clinics, including uses such as home care providers using mold systems. Another advantage of MSLO is that it can be operated with low light and therefore no pupil dilation is required.

  It should be appreciated that the method and apparatus embodiments described herein are not limited to application to the structural details and component arrangements set forth in the following description or illustrated in the accompanying drawings. It is. The method and apparatus can be implemented in other embodiments and can be implemented or performed in various ways. Specific implementation examples are presented herein for illustrative purposes only and are not intended to be limiting. In particular, acts, elements and features described with respect to any one or more embodiments are not intended to be excluded from a similar role in any other embodiments. Also, the terminology and terminology used herein is for the purpose of description and should not be considered limiting. The use of "including", "comprising", "having", "containing", "with", and variations thereof herein includes the items listed thereafter and equivalents thereof as well as additional items. The purpose is to do. Reference to “or” is intended to be inclusive so that any term written using “or” may indicate one, two, or all of the listed items. Can be interpreted.

  With reference to FIG. 1, a functional block diagram of an example of an MSLO according to one embodiment is illustrated. As described in more detail below, the MSLO 100 may include one or more laser illumination subassemblies 200 that generate an optical illumination beam 210 for scanning the human eyeball 110. In one example, laser illumination subassembly 200 includes one or more lasers configured to generate illumination beam 210 at a selected wavelength, as further described below. Laser illumination subassembly 200 may include or be coupled to focusing and / or collimating optics 220 to focus and / or collimate illumination beam 210. The illumination beam 210 travels through the cornea 112, the lens 114 and the fluid 116 via the optical subsystem 400 and is incident on the retina 118 of the eyeball 110. The illumination beam 210 is scanned across the retina 118 of the eyeball 110 using the MEMS scanning mirror 300. In one embodiment, as described further below, the MEMS scanning mirror 300 is a two-dimensional (2D) scanning mirror that scans the retina 118 with the illumination beam 210 in two dimensions. Light scattered by the retina 118 travels back through the eyeball 110 and is directed by the optical subsystem 400 to a return beam 510 that is detected by the optical detector subassembly 500. In one example, detector subassembly 500 includes optical component 520 and confocal aperture 530 to direct and focus return beam 510 onto detector 540, as described further below. The detector 540 can be, for example, a photomultiplier tube, an avalanche photodiode, or a charge coupled device (CCD).

  According to one embodiment, the entire MSLO subsystem 100 is encapsulated in a housing to allow automated self-retinal imaging to achieve the best focus of the illumination beam 210 on the retina 118 of the eyeball. Is electromechanically actuated to travel with 6 degrees of freedom. FIG. 2 is a block diagram illustrating an example of an MSLO device in which an optical subsystem is disposed within a housing / housing 600. In one embodiment, the housing 600 includes an eyepiece portion 610 that is configured to allow a patient to hold the device in his or her eye 110 to self-manage retinal scanning. The MSLO device may also include a controller 620 and a power source 630 located within the housing 600. In one example, power source 630 includes a battery. The power supply may provide power to any active components in the MSLO including the laser illumination subassembly 200 and the controller 620, for example.

  The controller 620 may be configured to control various components and operational aspects of the MSLO 100 to scan the patient's eye 110. For example, in embodiments that include the ability of one or more laser illumination subassemblies 200 to generate an illumination beam 210 at different wavelengths, the controller 620 may determine the wavelength of light used for illumination, and / or as described further below. Or it can control the order in which beams of different wavelengths are scanned. Controller 620 may further control any active components that may be included in MSLO 100. Controller 620 may further control the processing, storage, and / or transmission of the output from detector subassembly 500 to a remote location, as further described below. According to various examples, the controller 620 may be a Texas Instruments®, Intel®, AMD®, Sun®, IBM®, Motorola®, Freescale ( And a commercially available processor such as a processor manufactured by ARM Holdings. However, the controller 620 can be any type of processor, field programmable gate array, multiprocessor, or controller, whether commercially available or manufactured specifically.

  MSLO 100 may have any of a number of structures (examples described above) within housing 600. In some embodiments, the physical structure and / or configuration of the housing 600 and / or the placement of the MSLO 100, controller 620, and power supply 630 within the housing may be for the layout of the MSLO components and, optionally, for the MSLO. It can affect the selected optical configuration.

  Referring to FIG. 3, in conventional confocal scanning laser ophthalmoscope 800, irradiation beam 810 from irradiator 820 is scanned by scanning mirror 830, and the detection path is simultaneously descanned by the scanning mirror. A beam splitter 840 is used to separate the illumination path from the detection path and allow the illumination beam 810 and the return beam 850 to share a portion of the same optical path as shown in FIG. The front objective lens 860 focuses light on the eyeball 110 and the scanning mirror 830 and from the eyeball 110 and the scanning mirror 830. Although the illumination beam 810 can have a relatively small beam diameter, scattered light from the retina returning through a typical 3-5 mm diameter human pupil is caused by beam expansion in the return path from the front objective lens 860. The diameter can increase significantly in the scanning mirror. Dotted ray 870 represents scattered rays from the retina of eyeball 110. Therefore, in this conventional configuration, since the scanning mirror 830 is typically small, the free aperture of the scanning mirror may be significantly smaller than the beam diameter of the return beam. As a result, only a small portion of the light returning from the retina is reflected by the scanning mirror 830 towards the detector subassembly 500.

  To address this issue and improve collection efficiency, aspects and embodiments provide a confocal MSLO where the detection / collection path is not descanned. More precisely, as illustrated in FIGS. 4A and 4B, a beam splitter is arranged in the optical subsystem 400 to separate the irradiation path and the focusing path on the eyeball side of the scanning mirror 300. Beam splitter 410 either transmits illumination beam 210, referred to herein as a transmission architecture (FIG. 4A) (and reflects return beam 510), or is referred to herein as a reflective architecture (FIG. 4B). It can be configured to reflect the illumination beam 210 (and transmit the return beam 510). According to some embodiments, the optical subsystem 400 includes a scanning lens 420 and a field lens 430. Beam splitter 410 is positioned between scanning lens 420 and field lens 430 to capture all of the return light 510 from the retina and direct it to detector subassembly 500. Thus, the beam splitter 410 directs the return beam 510 to the detector subassembly 500 without descanning the return beam, reducing the complexity of the collection path for some prior confocal scanning laser ophthalmoscope configurations. Let

  As described above, in some embodiments, the front objective for MSLO (included in optical subsystem 400) is implemented using one or more on-axis refractive elements rather than off-axis reflective cone objectives. The For example, in the embodiment shown in FIGS. 4A and 4B, the front objective includes a field lens 430. The use of an on-axis refractive front objective reduces the complexity of the collection path aberrations that must be corrected in the illumination path and reduces the size of the MSLO (by eliminating the need for a large conical mirror). However, the addition of refractive elements to the common illumination and collection path can increase ghost reflection that effectively creates a bright spot in the center of the detected image. In a conventional scanning laser ophthalmoscope arrangement, such as the one illustrated in FIG. 3, for example, the detector 540 scans the scanning mirror so that light to be collected (from reflection from the retina) is descanned back to the detector. Located in a fixed location behind 830. In this configuration, ghost reflections can be blocked by an aperture pattern at a single location. In contrast, as described above, the MSLO embodiments described herein collect reflected light from the retina that is not descanned by placing the beam splitter 410 near the eyeball 110. In other words, the light constituting the return beam 510 is not reflected from the scanning mirror 300 after being reflected by the retina 118. As a result, ghost reflections seen in the collection path do not appear at a single location.

  According to one embodiment, the ghost reflection is greatly reduced by controlling the state of polarization in the illumination and collection paths so that the ghost reflection is polarized parallel to the illumination path and perpendicular to the collection path. Will be reduced. In one embodiment, this polarization control is achieved by using a polarizing beam splitter 410. In one example, polarizing beam splitter 410 is a cube beam splitter configured to preferentially transmit P-polarized light and reflect S-polarized light. Thus, for example, referring to FIG. 4B, assuming a reflective architecture and assuming that the illumination beam is S-polarized, the polarizing beam splitter 410 reflects S-polarized light and transmits orthogonal P-polarized light. The eyeball 110 is located in the reflective arm / path of the beam splitter 410 so that S-polarized light is incident on the refractive front objective lens (field lens 430) and the cornea of the eyeball. The ghost reflection maintains S polarization and is therefore not retransmitted through the beam splitter 410 to the detector subassembly 500. Reflections from the retina 118 are not polarized because they are caused by multiple scattering events. Accordingly, the portion of the reflection from the retina is P-polarized and retransmitted through beam splitter 410 to form return beam 510 at detector subassembly 500. If the angle of the light entrance surface to the scanning mirror 300 is parallel to the light entrance surface to the polarizing beam splitter 410, a reflective architecture may be preferred.

  Similarly, referring again to FIG. 4A, in the transmission architecture, the ghost reflection is polarized parallel to the illumination path, so that most is transmitted through the beam splitter 410 and not reflected back to the detector subassembly 500. In some examples, the transmission architecture may be preferred in configurations where the angle of the light entrance surface to the scanning mirror 300 is orthogonal to the light entrance surface to the polarizing beam splitter 410. This is because the scanning mirror reflects more S-polarized light than P-polarized light at 45 degrees. Thus, the polarizing beam splitter 410 forces ghost reflection to a power level much lower than the power level of reflection from the retina, effectively “blocking” or reducing the effects of ghost reflection in the image.

  As described above, in various embodiments of the MSLO 100 described herein, the scanning mirror 300 is a two-dimensional MEMS micromirror capable of high scanning speeds and large deflection angles. To illuminate a diffraction limited spot on the retina, the beam entering the eyeball 110 should be approximately parallel with a diameter of approximately 1-2 millimeters (mm; 0.039-0.079 inches). This beam diameter is determined by the optical properties of the human eye, and a 1 mm beam provides approximately minimum / maximum resolution in the eye. In one example, a 1 mm diameter beam in the cornea 112 allows a 10 micron (0.0004 inch) spot size on the retina. In order to image a standard retinal field of view, for example approximately 50 degrees, with a minimum optical reduction ratio of the illumination beam between the scanning mirror 300 and the cornea 112 of the eyeball, a scanning angle between the scanning mirror and the cornea There must be a minimum optical magnification. This is because the scan angle magnification from the curved front objective lens results in a corresponding beam diameter reduction. Therefore, it is desirable for the scanning mirror 300 to have a large scanning angle (angular motion range) and high scanning rate (velocity) in order to allow scanning of the retina's field of view before eye movement distorts the image.

  According to one embodiment, a two-dimensional scan of the retina 118 of the patient's eye 110 is performed by two-dimensionally scanning the retina 118 with the illumination beam 210. The two-dimensional MEMS scanning mirror 300 can be configured to achieve “raster” scanning by “tilting” in both dimensions over its angular range of motion. In one example, the scanning mirror 300 has a fast dimension and a slow dimension as in a conventional television raster scan. However, the scan need not be rectangular and the scanning mirror 300 may be configured to implement spiral or vector raster scanning.

  In one example, the power source 630 provides a fluctuating voltage to the two-dimensional MEMS scanning mirror 300 to actuate the mirror to move across its angular motion range (or selected portion thereof) for scanning. Scattered light from the retina 118 forms a return beam 510 that is collected by the detector subassembly 500. The detector 540 provides an output based on the detected return beam 510, and the output is processed to provide an image of the retina. Image processing of the detector output may be performed at least in part by the controller 620. In one example, the controller 620 includes a storage device (not shown) for storing (raw or processed) detector output to be provided to a remote user. For example, the controller may include a communication interface for transmitting the detector output to a remote location for processing and / or analysis, and the storage device may store data stored thereon on another machine. It may be removable from the housing 600 to allow processing and / or analysis. In one example, the storage device includes non-transitory computer readable random access memory, such as dynamic random access memory (DRAM), static memory (SRAM), or synchronous DRAM. However, a storage device may include any device for storing data, such as non-volatile memory, having sufficient throughput and storage capacity to support the functions described herein.

  In one embodiment, the scanning mirror 300 has a large deflection angle to allow scanning over a field of view of approximately 35-50 degrees at a sufficiently fast rate to mitigate the effects of eye movement during the imaging scan. It is realized using possible current high performance MEMS micromirror devices. In one example, the two-dimensional MEMS scanning mirror 300 has a resonance frequency greater than 23 kilohertz (kHz), a diameter of approximately 1.2 mm, and a mechanical deflection angle maximum between peaks of approximately 20 degrees in each axis ( Angular range of motion).

  According to an embodiment, the two-dimensional MEMS micromirror is operated with both axes being driven in resonance. In some cases where both axes of the scanning mirror resonate, the slow axis may not be slow enough for raster scanning to cover all field points in the field of view. Therefore, a non-repetitive Lissajous scan is used instead. A conventional raster scan pattern is generated when the fast scan axis frequency is an even multiple of the slow scan axis frequency. For large fields, the slow scan axis frequency must be significantly lower than the fast scan axis frequency in order to scan a line across the entire field. In contrast, a Lissajous pattern is generated when the ratio of the scan frequency for the fast scan axis compared to the slow scan axis is irrational. For this pattern, the slow scan axis frequency need not be much lower than the fast scan axis frequency.

  As described above, according to certain embodiments, the laser irradiation subassembly 200 of the MSLO may include a plurality of lasers configured to generate the irradiation beam 210 at a variety of different wavelengths. For example, as described further below, near infrared light may be used to image the retina and visible light may be used to present a fixation target to a human subject. The laser irradiation subassembly 200 can be implemented using any of a variety of different types of lasers. Multiple illumination beams may also be generated by multiple individual laser illumination assemblies 200 or using an array of lasers in one or more laser illumination subassemblies. Various laser irradiators may be used, and in any of the examples described and / or illustrated herein, one type or configuration of laser irradiation subassemblies is replaced with another. It should be recognized that it may be.

  With reference to FIG. 5, a functional block diagram of an example of a laser irradiation subassembly 200 according to one embodiment is illustrated. The laser illumination subassembly 200 includes one or more lasers configured to generate an illumination beam 210 at a selected wavelength. In one example, the MSLO may be configured for continuous near infrared (NIR) retinal image acquisition and image processing, and thus in this example, the laser illumination subassembly includes a near infrared laser 230. Additional wavelengths may be useful to obtain additional information from scanning the retina and / or to achieve additional functionality in the MSLO. For example, a visual fixation image on a patient whose retina is being scanned for improved contrast of retinal blood vessels and anemia (eg, green or yellow-orange laser irradiation) and / or as described further below. Visible irradiation may be used to provide As such, the laser illumination subassembly may include one or more visible lasers, such as a red laser 240 and / or a blue laser 250 as illustrated in FIG. As used herein, the term “visible laser” is intended to refer to a laser configured to emit a beam having a wavelength (or wavelength range) in the visible portion of the electromagnetic spectrum. Lasers 230, 240, and 250 may be any type of suitable laser light source, such as, for example, a laser diode or a fiber laser. Optical component 260 may be used to collimate the output beams from lasers 230, 240 and 250. In some embodiments, the laser packaging configuration and / or placement of the laser illumination subassembly within the housing of the MSLO can lead to one or more lasers not being directly aligned with the desired indication direction of the illumination beam 210. . Accordingly, a folding mirror 270 may be used to change the direction of the laser beam from one or more lasers. A beam splitter 280 may be used to allow different lasers to share the same optical path. An additional beam splitter may be placed immediately in front of the scanning mirror so that the laser beam incident on the mirror is perpendicular to the mirror surface when the mirror is stationary. This enables symmetric scanning in the four quadrants centered on the stationary position, and reduces any shape distortion caused in two dimensions by the nonlinear deflection angle.

  FIGS. 6A and 6B illustrate examples of MSLOs configured for multi-wavelength illumination with transmission and reflection architectures, respectively. Each of the irradiators 200a, 200b, and 200c may include any one or more of the lasers 230, 240, and / or 250 described above configured to laser at different wavelengths. In addition, each of the illuminators 200a, 200b, 200c can be individually and directly modifiable. As described above, the color combining beam splitter 280 may be used to combine the irradiation beams 210 of different wavelengths (colors) from each of the irradiators into the irradiation beam 210. The detector subassembly may include one or more color filters 560 that selectively pass the wavelength of the return beam 510 in the illustrated collection path. In the illustrated example, the detector subassembly includes filters 560a-c, each of which can be matched to the wavelength (or wavelength range) of the corresponding illuminator 200a, 200b, and 200c.

  The focusing optic 520 focuses the return beam 510 and directs it to the confocal aperture 530. A confocal aperture 530 can be used to filter light reflected from tissue layers outside the focal plane. As described above, detector 540 can be any type of suitable photodetector including, for example, an avalanche photodiode, CCD, or photomultiplier tube. The output from the detector can be stored and / or provided to the processor for analysis regardless of whether it is integrated with or remote from the MSLO (eg, controller 620).

  According to one embodiment, the MSLO includes an electrically adjustable lens 120 that is configured with a laser illumination subassembly 200 and a scanning mirror 300 as shown in FIGS. 6A and 6B. Can be positioned in the irradiation path between. The electrically adjustable lens 120 can be used for focus adjustment to better focus the illumination beam 210 on the retina 118 of the eyeball 110. In one example, the electrically adjustable lens 120 is an electrically adjustable liquid lens that can be adjusted or adjusted under the control of the controller 620.

  Referring to FIG. 7, in one embodiment, the MSLO further includes a focus and alignment path represented by dashed line 130. In this embodiment, the MSLO includes an illuminator 135. The irradiator 135 may use an irradiation source other than a laser, and generates an alignment beam that is directed to and from the eyeball 110 along the focusing and alignment path 130. An additional camera 140 optionally including associated focusing optics 145 may be included in the focusing and alignment path 130. A beam splitter 150 can be used to separate the forward and return paths and direct the returned alignment beam to the camera 140. Moreover, a dichroic beam splitter 155 can be used to separate the focusing and alignment path 130 from the collection path. For example, if NIR radiation is used for retinal imaging and thus the return beam 510 includes NIR wavelengths, the alignment beam may be in the visible spectral band. Thus, the dichroic beam splitter 155 can transmit NIR radiation to the detector subassembly 500 and reflect visible light to the beam splitter 150. Alternatively, if visible light is used for retinal imaging, the alignment beam may be an infrared beam, such as an NIR beam, and dichroic beam splitter 155 reflects NIR radiation and visible light is detected by a detector subassembly. 500 may be selected for transmission.

  In one example, the camera 140 is coupled to a processor 620 that is coupled to an electrically adjustable lens 120, and information from the focus and alignment path controls the electrically adjustable lens 120 to control the eye 110. It can be used to improve the focus of the illumination beam 210 on the retina 118. Information from the focus and alignment path 130 adjusts the positioning of the optical elements of the MSLO to allow adjustment of the position of the scan point on the eyeball and to image different regions of interest on the retina. Can also be used.

  According to another embodiment, the MSLO 100 may include a camera 160 and an illuminator 165 configured for continuous extraocular imaging, as shown in FIG. The camera 160 may be a small camera so as not to add significant dimensions or weight to the MSLO. The irradiator 165 can be, for example, a NIR irradiator. The illuminator can be modulated or perpendicularly polarized so as not to interfere with the MSLO imaging path.

  During operation of the MSLO, the human subject stares through the eyepiece 610 and the MSLO scans continuously across the retina 118 (eg, near infrared, approximately 780 nm) and captures a response at the detector 540. As described above, an internal feedback loop such as the focus and alignment path 130 can be used to adjust the position of the illumination beam on the retina 118. According to one embodiment, a fixation target is presented to a human subject and the subject's eye 110 is directed to a desired location / angle to obtain an image of a region of the retina 118. In one example, the fixation target is presented as an image formed by modulating a visible laser (eg, about 520 nm or about 635 nm) at the appropriate time during the scan. The image location may be automatically adjusted to guide the subject's eye to the best location for imaging, as further described below.

  With reference to FIG. 9, an example of an MSLO configured to provide a fixation target to a human subject during a scan is illustrated. The MSLO may include a display screen 170, such as an LCD screen, that displays the fixation target. The dichroic beam splitter 175 may be used to reflect the fixation target so that it is visible to the patient looking into the eyepiece 610 and can be used to guide the patient's gaze direction. A new retinal region can be imaged by adjusting the location of the fixation target on the display screen 170 and instructing the user to see the new target location. Presentation of a fixation target with real-time feedback to the patient and optional voice instructions advantageously enables fully automated, self-managed retinal imaging.

  In the embodiment described above with reference to FIG. 7, the focus and alignment path is superimposed on the light collection path. Alternatively, the focus and alignment path may be coupled to the illumination path, as illustrated in FIG. In this case, as shown in FIG. 9, a dichroic beam splitter 155 is used to synthesize the irradiation beam 210 and the alignment beam into a common optical path. As described above, information from the focus and alignment path is used to adjust the electrically adjustable lens 120 and / or to adjust the fixation target positioning to guide the patient's gaze direction. Can be.

  Another configuration of the MSLO including the fixation target displayed on the display screen 170 and the focusing and alignment path 130 is illustrated in FIG. In this example, the fixation target is divided into irradiation light paths using a beam splitter 175. Alternatively, the beam splitter 175 may be replaced with a Brewster window having an incident surface orthogonal to the incident surface of the irradiation beam to the scanning mirror 300.

  With reference to FIGS. 11A-11C, a flowchart of an example of a retinal imaging process according to one embodiment is illustrated. To initiate a scan, the first step 702 can include initializing a scan at a desired wavelength. For example, an imaging scan of the retina 118 can be performed using the near infrared laser described above. Step 702 may begin when the user turns on the MSLO device, for example. Initializing the imaging scan may include looking into the eyepiece and instructing the patient to open the eyeball 110 (step 704). As described further below, this indication may be audible (eg, the MSLO device may include a speaker (not shown) and the controller 620 may direct the speaker to emit the indication audibly). And / or visual. Initializing the imaging scan turns on the laser illumination subassembly 200, excites the laser at the desired wavelength (step 706), turns on the scanning mirror 300 (step 708), and the detector sub. Turning on assembly 500 (step 710) may also be included. As described above, turning on the scanning mirror 300 (step 708) provides a fluctuating voltage to the two-dimensional MEMS scanning mirror, causing the mirror to move continuously in each dimension in its deflection angle range. Controlling power supply 630 to operate may be included. As the two-dimensional MEMS scanning mirror moves, the illumination beam 210 is moved across the retina of the eyeball 110 to acquire an image of the retina (step 812).

  According to one embodiment, a first scan after initialization (step 702) is performed to determine whether the patient's eyeball 110 is correctly oriented for imaging the desired region of the retina and that the eyeball is aligned. Used to determine if you are in focus. Thus, the controller 620 processes the image acquired, for example, at step 712 by performing feature extraction processing (step 714) to locate specific locations in the image, such as iris, pupil and / or retina portions. obtain. Following the feature extraction process (step 714), the controller may determine whether the illumination beam is in focus on the iris of the eyeball 110 (step 716). If the iris is not in focus, the controller may move MSLO 100 (or some of its optical components) in the z direction (step 718). In one embodiment, the MSLO 100 is located within the housing 600 such that the MSLO (or at least some of its optical components) can move in the x-axis, y-axis, and z-axis (front-back, left-right, up-down). Can be mounted on a movable linear stage. After moving the MSLO in step 718, a new image is acquired in step 712 and processed in step 714 to determine whether the iris is in focus (step 716). This process can be repeated until the iris is correctly focused in the image.

  Controller 620 may then process the image to locate the pupil of eyeball 110 in the image (step 720) and determine whether the pupil is centered (step 722). If the pupil is not centered, the controller 620 may control the movable linear stage described above to move the MSLO 100 along the x-axis and / or y-axis until the pupil is at the center of the image (step 724).

  After initialization is complete, the system can perform one or more scans of the desired area of the retina using fixation target presentation with real-time feedback to enable fully automated, self-managed retinal imaging Can be configured. As described above, in one example, the retinal image is acquired using infrared irradiation. At the same time that the infrared scan is being performed, the visual illumination is appropriately modulated and the human eyeball is oriented to draw the fixation target in place so that it accurately images the desired area of the retina. Accordingly, with reference to FIGS. 11A-11C, in one embodiment, step 726 excites one or more visible lasers to emit a fixation target (step 728) and view the fixation target to the patient. Initiating a fixation process including issuing an audible instruction to (step 730). During the initial infrared setting scan described above, the fixation display 170 may be blank. When the fixation process is started, a fixation target is displayed on the screen 170 as exemplified in FIG.

  Initially, when the patient looks into the eyepiece 610, the eyeball 110 may not be correctly oriented, and thus the acquired eyeball image may be off-center. In one embodiment, the system acquires an image of the eyeball 110 using, for example, the infrared illumination described above (step 712), recognizes the pupil in the image (step 720), and determines whether the pupil is centered. (Step 722) If the pupil is not centered, the controller 620 may control the system to adjust the position of the fixation target (step 732) until the eyeball is oriented so that the pupil is at the center of the image. Controller 620 can then analyze the image to determine whether the retina is in focus (step 734) and move the MSLO or internal focusing optics in the z direction until the retina is in focus (step 734). 718). In some instances, the retina may be in focus, but the region of interest may not be visible. Accordingly, the controller 620 determines whether the exact region of the retina is visible (step 736), and if not, the fixation target can be moved to induce eye movement. The MSLO, or some of its optical components, may be moved laterally to compensate for the eyeball 110 tracking the fixation target.

  According to one embodiment, MSLO 100 is configured to provide binocular fixation (ie, a fixation target is presented to both eyes of a human patient). FIG. 13 illustrates an example of a configuration that provides binocular fixation. A certain percentage of the light intensity of the fixation target displayed on the display screen 170 is transmitted through the polarizing beam splitter 410 and reflected from the folding mirror 180 to the unimaged eyeball 110a. The remainder of the light intensity of the fixation target is transmitted through the polarizing beam splitter 410 to the imaged eyeball 110 as described above. This forces both eyes to look in the same direction, thus reducing the possibility of eye movement due to muscle disruption. FIG. 14 illustrates another MSLO configuration that provides binocular fixation.

  Referring again to FIGS. 11A-11C, according to one embodiment, once the setup is complete and the correct region of the retina is in focus, the MSLO is initialized (step 738) to obtain an image of the retina. One or more scans may be performed at a time. These scans may use infrared and / or visible illumination and may therefore be configured so that the laser used is turned on (if not turned on) to perform a full scan (step 740). . In one example, the system may issue a voice instruction to the patient not to blink during the scan (step 742). As described above, an image is acquired by scanning the entire retina with the illumination beam using the two-dimensional MEMS scanning mirror 300 (step 744). The image of interest can be stored for manual or automatic analysis. The various steps of the process can be repeated to acquire images of different regions of the retina and / or at different wavelengths to provide different information about the patient's retina. When all scans are complete, the system can be shut down including turning off the scanning mirror 300 (step 746), the laser illumination subassembly 200 (step 748), and the detector subassembly (step 750).

  Accordingly, aspects and embodiments provide a compact, wide-field scanning laser ophthalmoscope with a lightweight package that uses a two-dimensional MEMS micromirror for high-speed scanning, has few moving parts, and is robust and portable. Having all the optical components on the axis advantageously reduces aberrations. As mentioned above, including a common path lens may reduce the signal-to-noise ratio in some situations, but control of illumination and detection polarization by using a polarizing beam splitter counteracts the negative effects of the common path lens. Can do. Accordingly, wide field of view (eg, approximately 50 degrees) and broadband color correction (eg, ranging from approximately 450 nm to 800 nm) are provided in a lightweight package. In addition, as described above, an adjustable fixation target is presented to a human subject with real-time feedback and is fully automated (including automatic alignment, autofocus, autocapture / imaging) and self-managed retinal images May be possible. Embodiments of MSLO will allow for self-managed retinal imaging at any location, enable early diagnosis of eye diseases, reduce blindness and improve health around the world.

  Although several aspects of at least one embodiment have been described above, it will be appreciated by those skilled in the art who have the benefit of this disclosure that various changes, modifications, and improvements will readily occur. Such alterations, modifications, and improvements are intended to be part of this disclosure, and are intended to be within the scope of the invention. Accordingly, the foregoing description and drawings are by way of example only and the scope of the invention should be determined from the appropriate structure of the appended claims and their equivalents.

Claims (20)

A MEMS-based scanning laser ophthalmoscope,
A laser irradiation subassembly configured to generate a laser irradiation beam;
A two-dimensional MEMS scanning mirror configured to receive the laser irradiation beam and scan with at least a portion of the retina of the eyeball to be imaged with the laser irradiation beam;
An optical system optically coupled to the MEMS scanning mirror and configured to direct a laser irradiation beam from the scanning mirror to the eyeball to irradiate the retina of the eyeball;
A detector subassembly optically coupled to the optical system and configured to generate an image of the retina by blocking optical radiation reflected from the eyeball;
The optical system is positioned between the scanning mirror and the eyeball and is configured to direct a laser illumination beam to the eyeball and to direct optical radiation reflected from the eyeball to the detector subassembly. MEMS-based scanning laser ophthalmoscope including a beam splitter.   The MEMS-based scanning laser ophthalmoscope according to claim 1, wherein the two-dimensional MEMS scanning mirror is configured to scan the portion of the retina with a Lissajous pattern with a laser irradiation beam.   The MEMS-based scanning laser ophthalmoscope of claim 1, wherein the polarizing beam splitter is configured to transmit a laser illumination beam to an eyeball and direct optical radiation reflected from the eyeball to the detector subassembly.   The MEMS-based scanning laser ophthalmoscope of claim 1, wherein the polarizing beam splitter is configured to reflect a laser illumination beam to an eye and transmit optical radiation reflected from the eye to the detector subassembly.   The MEMS-based scanning laser ophthalmoscope according to claim 1, wherein the optical system further includes an on-axis objective lens positioned between the polarizing beam splitter and an eyeball.   The MEMS-based scanning laser ophthalmoscope of claim 1, wherein the detector subassembly includes a photodetector, and the photodetector includes one of an avalanche photodiode, a charge coupled device, and a photomultiplier tube.   The MEMS-based scanning laser ophthalmoscope of claim 6, wherein the detector subassembly further includes focusing optics configured to focus optical radiation on the photodetector.   The MEMS-based scanning laser ophthalmoscope of claim 7, wherein the detector subassembly further includes a confocal aperture optically coupled between the focusing optic and the photodetector.   The MEMS-based scanning laser ophthalmoscope of claim 1, wherein the laser illumination subassembly includes at least one of a near infrared laser light source and a visible laser light source. A display screen optically coupled to the optical system;
A controller configured to control the laser irradiation subassembly to display a fixation target on the display screen;
A dichroic beam splitter configured to optically couple the display screen to an irradiation path along which a laser irradiation beam travels to the eyeball, the irradiation path including the polarizing beam splitter, and the polarizing beam splitter The MEMS-based scanning laser ophthalmoscope of claim 1, wherein the eyeball is configured to direct light intensity corresponding to the fixation target to the eye to allow the eye to view the fixation target.   The controller is further configured to guide an eyeball orientation by adjusting a display location of the fixation target on the display screen to acquire an image of a selected region of the retina. MEMS-based scanning laser ophthalmoscope described in 1. An illuminator configured to provide an alignment beam;
A camera configured to detect the alignment beam reflected from the eyeball;
The MEMS-based scanning laser ophthalmoscope of claim 10, further comprising an alignment and focusing subsystem including a beam splitter configured to couple the alignment beam to the illumination path. An electrically adjustable lens positioned in the illumination path between the laser illumination subassembly and the scanning mirror;
The controller is coupled to the camera and the electrically adjustable lens, reflected from an eyeball, and based on information obtained from the alignment beam detected by the camera, of the electrically adjustable lens. The MEMS-based scanning laser ophthalmoscope of claim 12, further configured to adjust the focus. A method of imaging the retina of an eyeball with a scanning laser ophthalmoscope, the method comprising:
Generating a laser irradiation beam;
Directing the laser beam to the eyeball by means of a polarizing beam splitter;
Scanning with a laser irradiation beam around a scanning point in the eyeball using a two-dimensional MEMS scanning mirror to generate a two-dimensional irradiation region for irradiating the retina of the eyeball;
Directing optical radiation reflected from the eyeball to the detector subassembly by the polarizing beam splitter without descanning the optical radiation;
Generating an image of the retina from the optical radiation.   The method of claim 14, wherein generating the laser irradiation beam includes generating at least one of a near infrared irradiation beam and a visible irradiation beam.   The method of claim 14, wherein scanning with the laser irradiation beam comprises scanning the laser irradiation beam with a Lissajous pattern.   The polarizing beam splitter is positioned between the scanning mirror and the eyeball, and directing a laser irradiation beam to the eyeball includes transmitting the laser irradiation beam through the polarization beam splitter and reflected from the eyeball The method of claim 14, wherein directing optical radiation to the detector subassembly includes reflecting optical radiation by the polarizing beam splitter.   The polarizing beam splitter is positioned between the scanning mirror and the eyeball, and directing the laser irradiation beam to the eyeball includes reflecting the laser irradiation beam by the polarizing beam splitter and reflected from the eyeball The method of claim 14, wherein directing optical radiation to the detector subassembly includes transmitting optical radiation through the polarizing beam splitter. Irradiating the eyeball with an alignment beam;
Detecting the alignment beam;
Adjusting the focus of an electrically adjustable lens positioned between a laser irradiation subassembly that generates the laser irradiation beam and a scanning mirror to focus the laser irradiation beam on the retina of an eyeball; 15. The method of claim 14, further comprising: Displaying a fixation target on the display screen;
The method of claim 14, further comprising: adjusting a display location of the fixation target on the display screen to derive an eyeball orientation to obtain an image of a selected region of the retina.

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