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WO2025165910A1 - Dispositif ophtalmoscopique et procédé de capture d'images l'utilisant - Google Patents

Dispositif ophtalmoscopique et procédé de capture d'images l'utilisant

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Publication number
WO2025165910A1
WO2025165910A1 PCT/US2025/013648 US2025013648W WO2025165910A1 WO 2025165910 A1 WO2025165910 A1 WO 2025165910A1 US 2025013648 W US2025013648 W US 2025013648W WO 2025165910 A1 WO2025165910 A1 WO 2025165910A1
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WO
WIPO (PCT)
Prior art keywords
eye
light
illumination
lens
anterior segment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/013648
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English (en)
Inventor
Jaya Devi CHIDAMBARAM
Dongkyun Kang
Kenneth MARCELINO
Momoka SUGIMURA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Manchester
University of Arizona
Original Assignee
University of Manchester
University of Arizona
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Manchester, University of Arizona filed Critical University of Manchester
Publication of WO2025165910A1 publication Critical patent/WO2025165910A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/0008—Microscopes having a simple construction, e.g. portable microscopes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/1025—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for confocal scanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/117—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for examining the anterior chamber or the anterior chamber angle, e.g. gonioscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0028—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders specially adapted for specific applications, e.g. for endoscopes, ophthalmoscopes, attachments to conventional microscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0052—Optical details of the image generation
    • G02B21/0064—Optical details of the image generation multi-spectral or wavelength-selective arrangements, e.g. wavelength fan-out, chromatic profiling
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/10—Beam splitting or combining systems
    • G02B27/1006—Beam splitting or combining systems for splitting or combining different wavelengths
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/10—Beam splitting or combining systems
    • G02B27/1086—Beam splitting or combining systems operating by diffraction only
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions

Definitions

  • anterior segment eye diseases traditionally involves the initial assessment by an ophthalmologist performing eye examination using a slit lamp biomicroscope.
  • a corneal scrape is acquired for microbiologic testing to obtain the final diagnosis and can take up to 7 to 14 days for culture results to return for more fastidious organisms (e.g., fungi or Acanthamoeba sp.). This can delay the start of the correct treatment, resulting in worsening of the disease and contributing to poor visual outcomes.
  • fastidious organisms e.g., fungi or Acanthamoeba sp.
  • the disclosed embodiments relate to low-cost, portable in-vivo confocal ophthalmoscopes (PICOs) and associated methods that, among other features and benefits, provide microscopic images of the anterior segment of the eye and the external eye structures enabling visualization of cellular and some sub-cellular structures.
  • PICOs portable in-vivo confocal ophthalmoscopes
  • Some of the features of the disclosed embodiments include the use of a non-contact objective lens in conjunction with a grating-based, scan-less confocal microscopy approach; integration of the capability of imaging the external eye and anterior segment en face, integration of a display as part of the microscope, and attachment methods onto a slit lamp biomicroscope or for hand-held use.
  • FIG. 1 illustrates an optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 2 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 3 illustrates another optical configuration of an ophthalmoscope with multislit masks accordance with an example embodiment.
  • FIG. 4 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 5 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 6 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 7 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 8 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 9 illustrates another optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • FIG. 10 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • FIG. 11 illustrates side and top views of collimation optics, illumination pupil and detection pupil of an ophthalmoscope positioned in a first configuration in accordance with an example embodiment.
  • FIG. 12 illustrates side and top views of collimation optics, illumination pupil and detection pupil of an ophthalmoscope positioned in a second configuration in accordance with an example embodiment.
  • FIG. 13 illustrates centered and decentered positions of an objective lens of an ophthalmoscope positioned in accordance with an example embodiment.
  • FIG. 14 shows front and side view diagrams, illustrating how an example ophthalmoscope device can be positioned to acquire images without contacting the eye in accordance with some embodiments.
  • FIG. 15 shows an example diagram of an ophthalmoscope device that is mounted on a slit lamp biomicroscope in accordance with an example embodiment.
  • FIG. 16 illustrates positioning of an ophthalmoscope device without contacting a patient’s eye in accordance with an example embodiment.
  • FIG. 17 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • IVCM In vivo confocal microscopy
  • HRT3-RCM Rostock Cornea module
  • the limitations of this device include: direct contact of the device with the patient’s eye being required for image acquisition, a small field of view (0.4 x 0.4 mm 2 ), automated imaging limited to only 80 micron depths after which refocusing is required for further image acquisition at deeper planes, slow imaging speed (30 frames/sec), the external camera enabling only very limited ocular surface digital photo to be obtained mainly from the lateral side of the anterior eye not en face (i.e. , from the front, facing the eye), the high cost of the device, and limited device portability.
  • OCT optical coherence tomography
  • high-resolution OCT is expected to have a high device cost, similar to HRT3, due to the need for expensive light sources and deep-well complementary metal oxide semiconductor (CMOS) sensors.
  • CMOS complementary metal oxide semiconductor
  • PCM portable confocal microscopy
  • the disclosed embodiments overcome the shortcomings of prior systems, and among other features and benefits, enable non-invasive and rapid imaging of the eye without contacting the eye.
  • Use of gratings to produce confocal images helps to keep the device small, portable and low-cost.
  • the lack of moving components such as scanning mirrors contributes to the robustness and compact nature of the overall device structure that also enables portability of the device.
  • the lack of scanning mirrors also means that the imaging speed is not slowed down or limited by the mirror movement.
  • the use of multi-slit masks in some embodiments increases the signal level and imaging speed.
  • the use of multi-slit masks also avoids widening of the slit width and ensures that the resolution does not degrade to increase the signal level.
  • the disclosed embodiments that utilize a wide-field imaging module enable a larger en face color image of the cornea/ocular surface/eyelids to be obtained, rather than having to obtain images from the lateral side (as per the HRT3-RCM IVCM); this allows for better positioning of the confocal microscopy imaging area in the tissue region of interest and also enables the same region of interest to be imaged when repeat imaging is performed at a later point in time. Also, the en face color image enables visualization and establishment of a record of any pathology visible on the ocular surface/eyelids, that can be compared at repeat imaging visits to aid in the assessment of treatment responses.
  • One of the features of the disclosed microscopes is their capability to be used as an imaging device that can visualize cellular and in some instances subcellular morphologic changes in various diseases of the anterior segment of the eye (such as cornea, conjunctiva and limbal region), and external eye structures (such as eyelid structures including meibomian glands and conjunctiva lining the eyelids) of the patient.
  • This enables rapid point of care in vivo, in-clinic diagnosis that can lead to timely intervention and treatment.
  • the disclosed devices are relatively low cost in comparison with the current market competition due in-part to a lack of moving components.
  • the disclosed devices can be designed to attach to standard slit lamp biomicroscopes that are already in widespread use in most ophthalmology clinics worldwide, and this allows for these devices to be easily integrated into the standard eye examination infrastructures and procedures, i.e. enabling ease of incorporation into current diagnostic and imaging workflow pathways in ophthalmology clinics. Since the disclosed devices allow for more rapid, non-contact imaging of the anterior eye in a portable format, and can be used either as a hand-held device or via a slit lamp biomicroscope attachment, they can be utilized in a variety of eyecare settings (such as community or hospital-based services) and could be utilized readily by a variety of device operators (such as ophthalmic photographers, optometrists, as well as ophthalmologists).
  • FIG. 1 illustrates an optical configuration of an ophthalmoscope in accordance with an example embodiment.
  • a light source such as a light emitting diode (LED)
  • a condenser Light that is spatially filtered by the illumination slit is collimated by collimation lens 1 , reflected by a mirror, and diffracted by grating 1.
  • the mirror is used to fold the optical path as a space-saving mechanism and is not strictly required for the operation of the device but aids in reducing the overall size of the device.
  • the diffracted light produced by grating 1 includes spectrally dispersed (diffracted) light that is then focused by a dry-immersion objective lens at different lateral positions at the focal plane of the objective lens.
  • the objective lens in a preferred embodiment, has a numeral aperture (NA) that is larger than 0.5 and a long working distance that is larger than 5 mm. In one example embodiment, the working distance is 13 mm.
  • NA numeral aperture
  • the working distance is 13 mm
  • Use of a dry-immersion lens makes it possible to image the anterior segment of the eye (e.g., cornea) without making physical contact with the ocular surface. Light reflected from the region of interest in the anterior segment of the eye or external eye structures is collected by the same objective lens and combined by grating 2.
  • Grating 2 directs the light to a focusing lens, which focuses the light onto the single detection slit.
  • Light that is spatially filtered by the single detection slit is collimated by collimation lens 2 and dispersed by grating 3.
  • the dispersed light is then focused by a camera lens onto a detector, such as a complementary metal oxide semiconductor (CMOS) sensor, to generate a two-dimensional confocal image.
  • CMOS complementary metal oxide semiconductor
  • the light source in FIG. 1 is a broadband light source.
  • the center wavelength of light source is in the range 800-850 nm, with a spectral bandwidth in the range 30-50 nm.
  • FIG. 2 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • This configuration includes a polarizer after collimation lens 1 in the illumination path (e.g., linear polarizer 1 ) and another polarizer before the focusing lens on the detection path (e.g., linear polarizer 2) that is perpendicular to linear polarizer 1 to achieve cross-polarized detection.
  • the remaining components of FIG. 2 are similar to those in FIG. 1.
  • Use of a dry-immersion lens in the disclosed embodiments can generate a strong specular reflection from the air-to-cornea interface. The specular reflection could overwhelm the signals from sub-surface cellular structures.
  • the embodiment illustrated in FIG. 2 reduces the amount of specular reflection from the tissue surface by illuminating and detecting the light that is in a particular polarization state, thus facilitating imaging of sub-surface cellular structures.
  • the single slit used in the previous two example embodiments determines the resolution and the amount of light that is incident on the cornea.
  • a narrow slit is needed to achieve high resolution; however, such a slit may provide weak illumination power on the cornea due to, for example, the inefficiency in coupling light from an extended light source to a narrow slit.
  • FIG. 3 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment, in which the single-slit masks are replaced with multi-slit masks.
  • Use of multiple slits makes multiple wavelengths to be incident on the same point of the tissue and therefore increases the illumination power.
  • the width of each slit can stay small, which ensures that the resolution is not degraded.
  • collimation lens 1 , focusing lens, and collimation lens 2 are chosen or developed so that the field curvature over the field angle used for PICO imaging (preferably larger than ⁇ 2.5°) is smaller than the effective depth of focus of each of the lenses on the non-collimating side. This embodiment ensures that the effective focused line on the tissue stays sharp when light from the multiple slits is focused to a single line on the tissue.
  • FIG. 4 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • the components in FIG. 4 are similar to those in FIG. 3, but the configuration of FIG. 4 includes a linear polarizer after collimation lens 1 in the illumination path and another linear polarizer before the focusing lens on the detection path to achieve cross-polarized detection.
  • This embodiment reduces the amount of specular reflection from the tissue surface and facilitates imaging of subsurface cellular structures similarly to the second embodiment.
  • FIG. 5 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • This configuration incorporates camera lens 2 and sensor 2 (e.g., a CMOS sensor).
  • Camera lens 2 in conjunction with the objective lens generates wide-field images of the entire eye on CMOS sensor 2.
  • the ophthalmoscope has a relatively small FOV and is only able to produce images from a small region of interest, the inclusion of the additional camera lens and sensor allows images with a large FOV to be captured, which enables capture of a color image of the ocular surface, and helps with positioning the ophthalmoscope imaging area on the region of interest on the patient’s eye.
  • the FOV of the ophthalmoscope device can be 1 -2 mm, whereas the FOV of the additional camera lens can be 10 mm or more.
  • the additional camera lens and sensor can capture images using ambient light or utilize a separate light source (not shown).
  • the remaining components in FIG. 5 are similar to those in FIG. 1 .
  • FIG. 6 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • the configuration in FIG. 6 incorporates camera lens 2 and CMOS sensor 2 as an attachment to the confocal ophthalmoscope device.
  • CMOS sensor 2 as an attachment to the confocal ophthalmoscope device.
  • wide-field images of the entire cornea and adjacent ocular surface are acquired without having to use the light that passes through the objective lens, which can make it easier to achieve a large field of view.
  • the remaining components in FIG. 6 are similar to those in FIG. 5.
  • FIG. 7 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • FIG. 7 configuration incorporates a display as part of the confocal ophthalmoscope device.
  • the display e.g., an LED or LCD display
  • the display that is coupled to the sensor and displays the images obtained based on the signals sensed by the CMOS sensor of the confocal ophthalmoscope device in real time; this feature makes it easier to adjust the confocal ophthalmoscope device for the imaging region of interest, area and depth.
  • FIG. 8 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • This configuration adds a display as part of the ophthalmoscope device shown in FIG. 5.
  • the display shows confocal microscopy images and wide-field images in real time (e.g., in separate or side-by-side windows), which makes it easy to adjust the ophthalmoscope device for the imaging region of interest, area and depth.
  • FIG. 9 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • This configuration adds a display as part of the ophthalmoscope device shown in FIG. 6.
  • the display shows confocal microscopy images and wide-field images in real time, which makes it easy to adjust the ophthalmoscope device for imaging region of interest, area and depth.
  • FIG. 10 illustrates an optical configuration of another ophthalmoscope in accordance with an example embodiment.
  • Light from a superluminescent diode (sLED) is collimated by collimation lens 1.
  • Collimated light is shaped into a line illumination by a cylindrical lens.
  • Line illumination is collimated by collimation lens 2, reflected by a mirror, and diffracted by grating 1.
  • the diffracted light is then focused by a dry-immersion objective lens with an adequate numerical aperture (preferably larger than 0.5) and a long working distance (preferably larger than 5 mm).
  • Light reflected by cornea is collected by the same objective lens and diffracted by grating 2.
  • Grating 2 directs the light to a focusing lens, which focuses the light onto the single detection slit.
  • the configuration of FIG. 10 provides a higher illumination power, which in turn increases the signal strength.
  • the configuration of FIG. 10 provides a similar illumination power but without any sidelobe artifacts that may be caused by the multiple slits. Accordingly, the use of sLED increases the signal level and imaging speed.
  • FIGS. 11 and 12 illustrate optical configuration modifications to an ophthalmoscope in accordance with some example embodiments.
  • the modifications cause divergence of the illumination beam in one direction while maintaining focus in the orthogonal direction. This is done by adjusting, for example, the distance between the sLED and collimation lens 1 in the configuration of FIG. 10.
  • FIGS. 11 and 12 show the position of the sLED with respect to collimation lens 1 and the resulting collimation quality of light between collimation lens 1 and the cylindrical lens. The figures also illustrate the behavior of light as it travels from the objective lens to the eye.
  • FIG. 11 shows the side and top views when the light from the sLED is collimated by collimation lens 1 , and the illumination generated by the objective lens on the cornea surface is collimated.
  • the top two diagrams of FIG. 11 illustrate a side view of the generation of the collimated illumination beam (top left), and its delivery to the eye and the resulting reflections from the surface of the cornea (top right).
  • the reflected light from the cornea surface slightly diverges and passes through the detection pupil, the center of which corresponds to the center of the illumination pupil from the side view, which is at the same height as the illumination pupil from the side view. While the slight divergence of the reflected beam makes the beam defocused from the detection slit, a significant portion of the reflected light still passes through the detection slit.
  • the bottom two diagrams of FIG. 11 illustrate a top view of the generation of the collimated illumination beam (bottom left), and its delivery to the eye and the resulting reflections from the surface of the cornea (bottom right). Both the illumination slits and detection slits are illustrated in the bottom right diagram.
  • FIG. 12 using similar side and top views as in FIG. 11 , demonstrates how displacing collimation lens 1 relative to the sLED results in a diverging beam at the surface of the eye.
  • the reflected light from the corneal surface diverges significantly, as evident by comparing the top right diagrams of FIG. 11 and FIG. 12. Therefore, the specular reflection from the cornea surface is first reduced by the limited size of the detection pupil and further reduced by the detection slit due to the larger defocus of the specular reflection relative to the detection slit. Accordingly, the detected specular reflection from the cornea surface is reduced.
  • FIG. 13 illustrates another optical configuration modification to an ophthalmoscope in accordance with some example embodiments.
  • it illustrates decentering the objective lens relative to the center of the illumination and detection pupils from the side view to reduce specular reflection detected from the apex of the cornea.
  • Panel A illustrates the arrangement where the center of the illumination pupil is in line with the optical axis of the objective lens. This arrangement results in a normally-incident chief ray on the cornea apex from the side view. This arrangement makes the specular reflection from the cornea apex have the same propagation angle for the chief ray from the side view, which increases the detection efficiency of the specular reflection and degrades the capability for visualizing weakly-scattering cellular structures.
  • Panel B in FIG. 13 depicts the arrangement where the center of the illumination pupil is decentered relative to the optical axis of the objective lens. This arrangement makes the chief ray from the illumination pupil incident on the cornea apex at an angle. The specular reflection from the cornea apex propagates at an angle different from the incidence angle, and is blocked by the detection pupil, the center of which corresponds to the center the illumination pupil from the side view. This arrangement reduces the detection of the specular reflection from the cornea apex.
  • FIG. 14 illustrates example front and side views of how the ophthalmoscope device can be positioned to acquire the desired images without contacting the eye.
  • the ophthalmoscope device PICO
  • PICO ophthalmoscope device
  • This arrangement allows a clear line of sight for the non-imaged eye to enable the patient to focus on a target, in order to, for example, bring the fellow to-be-imaged eye into the correct position; in this way, the region of interest to be imaged falls into the field of view of the ophthalmoscope device.
  • This arrangement also provides more comfort to patients by not blocking the non-imaged eye’s view, and thereby reducing any feeling of claustrophobia.
  • FIG. 15 shows an example ophthalmoscope device mounted on a slit lamp biomicroscope using an adapter.
  • the ophthalmoscope device includes, or is coupled to its own light source, and thus the slit lamp can be used as a convenient fixture for mounting the ophthalmoscope device (rather than using the slit lamp as an illumination source).
  • the adapter facilitates positioning of the ophthalmoscope device relative to the patient’s to-be-imaged eye using the existing mechanical adjustment methods in the slit lamp (for example, joystick used for forwards/backwards and lateral movement, and chinrest for adjusting the patient’s head and eye position relative to the in vivo confocal ophthalmoscopic device).
  • the adapter also provides a stable mounting of the PICO device.
  • the patient may place his/her head on the slit lamp biomicroscope chin rest and forehead against the slit lamp head rest, and this will stabilize the patients’ head and eye position, while the in vivo confocal ophthalmoscope device itself is positioned to focus on the region of interest to be able to acquire the desired images without contacting the eye.
  • FIG. 16 illustrates an example ophthalmoscope device with an attachment that protrudes from the device and contacts the skin (e.g., of the orbital rim) on the patient’s face while not making contact between the objective lens and eye.
  • the attachment contacts the orbital rim on the external aspect of the eyelid skin.
  • the attachment can have a square, rectangular or circular shape with a hollow interior that surrounds the patient’s eye and allows light from the ophthalmoscope device to reach the eye, and the reflected light to be collected by the ophthalmoscope device, through the hollow interior.
  • the attachment can be a solid structure that contacts only the forehead, or an upper section of the orbital rim, without obscuring the light path between the ophthalmoscope device and the eye.
  • the attachment can be made of a rigid, semi-rigid or elastic material, and can also be made to be translucent, thereby reducing any sensation of claustrophobia for the patient.
  • this attachment enables a reduction in fine movements of the ophthalmoscope device (either from the operator’s hand movements if utilizing the device as hand-held or from the patient’s head movements) and thereby aims to reduce movement artefacts in the acquired ophthalmoscope images, thereby maintaining good image quality.
  • This embodiment highlights the potential of the disclosed ophthalmoscope devices to be used as a handheld device that does not need to be attached to a slit lamp biomicroscope, but could also be utilized when the device is attached to the slit lamp if required.
  • FIG. 17 illustrates an example ophthalmoscope device with a motorized translation stage that scans the objective lens axially to acquire images at different depths of the tissue.
  • the translation stage can scan the objective lens at the speed of 0.2-0.5 mm/sec while the CMOS sensor acquires the image data at the rate of 100 frames/sec. This results in the axial scanning step size of 2-5 pm between two sequential confocal microscopy images, and rapid completion of scanning of a tissue thickness of 500 pm within 1-2.5 seconds or tissue thickness of 1000 pm within 2-5 seconds.
  • a battery is included as part of the ophthalmoscope and electrically connected to the motorized translation stage and LED, making the ophthalmoscope operatable without the connection to the mains electricity supply via the wall power outlet.
  • One aspect of the disclosed embodiments relates to a confocal ophthalmoscope device that includes one or more illumination slits positioned to receive broadband illumination from a light source, a first grating configured to receive light corresponding to the one or more illumination slits and to produce spectrally-dispersed light, and an objective lens positioned to receive the spectrally-dispersed light for illumination of an anterior segment of an eye.
  • the objective lens is a dry objective lens lacking any immersion media in contact therewith, the objective lens is positioned to be at a distance from the eye without contacting the anterior segment of the eye, and the objective lens is positioned to receive reflected light from the anterior segment of the eye upon illumination with the spectrally-dispersed light.
  • the confocal ophthalmoscope device further includes a second grating positioned to receive light corresponding to the reflected light from the anterior segment of the eye and collected by the objective lens, a focusing lens positioned to receive light from the second grating, one or more detection slits positioned at a focal distance of the focusing lens, a collimation lens positioned to receive light from the one or more detection slits, and a third grating positioned to receive light from the collimation lens and to generate an output spectrally-separated light for producing images corresponding to one or more regions of interest of the anterior segment of the eye.
  • the confocal ophthalmoscope device includes a first camera lens and a first detector positioned to receive the output spectrally-separated light.
  • the confocal ophthalmoscope includes another collimation lens positioned between the one or more illumination slits and the first grating.
  • the confocal ophthalmoscope device includes a folding mirror positioned between the one or more illumination slits and the first grating.
  • the spectrally-dispersed light for illumination of the anterior segment of the eye and the reflected light from the anterior segment of the eye are incident on different, non-overlapping sections of the objective lens.
  • the confocal ophthalmoscope device includes the light source that is operable at a center wavelength in the range 800-850 nm and a bandwidth in the range 30-50 nm.
  • the confocal ophthalmoscope device further includes a first polarizer positioned in a light path between the one or more illumination slits and the first grating, and a second polarizer positioned in a light path between the second grating and the one or more detection slits.
  • the confocal ophthalmoscope device includes a first camera lens and a first detector positioned to receive the output spectrally-separated light, and a second camera lens and a second detector positioned to capture one or more images of the eye at a larger field of view (FOV) compared to an FOV associated with the images corresponding the one or more regions of interest of the anterior segment of the eye.
  • FOV field of view
  • the FOV corresponding to the second camera lens and a second detector is 10 mm or more, and the FOV associated with the images corresponding the one or more regions of interest of the anterior segment of the eye is in a range 1-2 mm.
  • the second camera lens and a second detector are positioned at an oblique angle with respect to an optical axis of the objective lens so as to receive light that is reflected from the eye without traversing through the objective lens.
  • the one or more illumination slits comprise more than one illumination slits
  • the one or more detection slits comprise more than one detection slit.
  • the confocal ophthalmoscope device includes an additional collimation lens positioned between first grating and the one or more illumination slits, wherein the collimation lens, the focusing lens, and the additional collimation lens are selected so that a field curvature over a field angle used for imaging is smaller than an effective depth of focus, on a non-collimating side, for each of the collimation lens, the focusing lens, and the additional collimation lens.
  • the confocal ophthalmoscope device further includes an attachment positioned at an interior of the confocal ophthalmoscope device to allow contact with a section of a face of a patient outside of the eye and to allow positioning of the confocal ophthalmoscope device against the patient’s face at a distance from a surface of the eye.
  • the confocal ophthalmoscope device is coupled to a slit lamp of a microscope.
  • the confocal ophthalmoscope further includes a display to enable viewing of one or both of: the images corresponding to one or more regions of interest of the anterior segment of the eye at a first FOV, or an image of the eye with a second FOV that is higher than the first FOV.
  • the confocal ophthalmoscope device does not include any scanning or moving elements.
  • the confocal ophthalmoscope device is a hand-held device configured to be held in position in front of the eye.
  • a confocal ophthalmoscope device that includes one or more illumination slits positioned to receive broadband illumination from a light source, a first dispersive device positioned to receive light corresponding to the one or more illumination slits from a first collimation lens to produce spectrally-dispersed light, and an objective lens positioned to receive the spectrally-dispersed light for illumination of an anterior segment of an eye.
  • the objective lens is a dry objective lens lacking any immersion media, the objective lens is positioned to be at a distance from the eye without contacting the anterior segment of the eye, and the objective lens is positioned to receive reflected light from the anterior segment of the eye upon illumination with the spectrally-dispersed light.
  • the confocal ophthalmoscope device further includes a second dispersive device positioned to receive light corresponding to the reflected light from the anterior segment of the eye and collected by the objective lens, a focusing lens, one or more detection slits and a second collimation lens positioned to receive light from the second grating, a third dispersive device positioned to receive light from the second collimation lens and to generate an output spectrally-separated light, and a detector positioned to produce images corresponding to one or more regions of interest of the anterior segment of the eye based on the output spectrally-separated light.
  • the first, second or the third dispersive device is one of a grating, prism or an optical fiber.
  • the confocal ophthalmoscope device includes a camera lens and a second detector positioned to capture one or more images of the eye at a larger field of view (FOV) compared to an FOV associated with the images corresponding the one or more regions of interest of the anterior segment of the eye, wherein the one or more images of the eye at a larger field of view (FOV) and the images corresponding the one or more regions of interest of the anterior segment of the eye are produced simultaneously.
  • the confocal ophthalmoscope device does not include any scanning or moving elements, and the ophthalmoscope device is a hand-held device configured to be held in position in front of the eye.
  • the objective is configured to provide the spectrally-dispersed light for illumination of an external eye structure
  • the second grating is configured to receive light corresponding light from the external eye structure
  • the images correspond to the one or more regions of interest of the external eye structure.
  • a confocal ophthalmoscope device that includes a first collimation lens positioned to receive light from a superluminescent diode (sLED) light source, and a cylindrical lens positioned to receive illumination from the first collimation source and direct the illumination received thereon to a second collimation lens.
  • the confocal ophthalmoscope device also includes a first grating configured to receive illumination associated with the second collimation lens and to produce spectrally-dispersed light, and an objective lens positioned to receive the spectrally-dispersed light for illumination of an anterior segment of an eye or an external eye structure.
  • the objective lens is a dry objective lens lacking any immersion media in contact therewith to allow the objective lens to be positioned at a distance from the eye without contacting the anterior segment of the eye and to receive reflected light from the anterior segment of the eye or the external eye structure upon illumination with the spectrally-dispersed light.
  • the confocal ophthalmoscope device also includes a second grating positioned to receive light corresponding to the reflected light from the anterior segment of the eye, or the external eye structure, and collected by the objective lens, a focusing lens positioned to receive light from the second grating, at least one detection slit positioned at a focal distance of the focusing lens, a third collimation lens positioned to receive light from the at least one detection slit, and a third grating positioned to receive light from the third collimation lens and to generate an output spectrally- separated light for producing images corresponding to one or more regions of interest of the anterior segment of the eye or the external eye structure.
  • the first collimation lens is positioned at a defocused location with respect to a location of the sLED to, upon activation of the sLED light source, produce a diverging illumination that is incident on the cylindrical lens, thereby causing divergence of the reflected light from the anterior segment.
  • the objective lens is positioned at a decentered location with respect to an optical axis associated with an illumination pupil and a detection pupil of the confocal ophthalmoscope device.
  • the confocal ophthalmoscope device includes a translation stage operable to scan the objective lens in a lateral direction to allow acquisition of the images in a sequence.
  • a scan rate associated with the translation stage enables completion of scanning of a tissue thickness of 500 pm within 1-2.5 seconds or a tissue thickness of 1000 pm within 2-5 seconds.
  • the confocal ophthalmoscope device includes one or more batteries coupled to one or both of the sLED or the translation stage to allow battery- only operations of the confocal ophthalmoscope device.
  • various components may be controlled or various operations may be performed via implementations using a processor/controller that is configured to include, or be coupled to, a memory that stores processor executable code that causes the processor/controller carry out various computations and processing of information.
  • the processor/controller can further generate and transmit/receive suitable information to/from the various system components, as well as suitable input/output (IO) capabilities (e.g., wired or wireless) to transmit and receive commands and/or data.
  • IO input/output
  • the processor/controller may, for example, provide signals to control the operation of various components such as light sources and detectors that are disclosed herein.
  • Various information and data processing operations described herein may be implemented in one embodiment by a computer program product, embodied in a computer-readable medium, including computer-executable instructions, such as program code, executed by computers in networked environments.
  • a computer-readable medium may include removable and non-removable storage devices including, but not limited to, Read Only Memory (ROM), Random Access Memory (RAM), compact discs (CDs), digital versatile discs (DVD), cloud storage, etc. Therefore, the computer-readable media that is described in the present application comprises non-transitory storage media.
  • program modules may include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types.
  • Computer-executable instructions, associated data structures, and program modules represent examples of program code for executing steps of the methods disclosed herein. The particular sequence of such executable instructions or associated data structures represents examples of corresponding acts for implementing the functions described in such steps or processes.

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Abstract

Des ophtalmoscopes confocaux in vivo portables (PICO) à faible coût et des procédés associés sont décrits, qui permettent de produire des images microscopiques du segment antérieur de l'œil et des structures oculaires externes permettant la visualisation de structures cellulaires et de certaines structures sous-cellulaires. Certaines des caractéristiques des ophtalmoscopes décrits portent sur l'utilisation d'une lentille objectif sans contact conjointement avec une approche de microscopie confocale sans balayage basée sur un réseau, l'intégration de la capacité d'imagerie de l'œil externe et du segment antérieur en face, l'intégration d'une unité d'affichage en tant que partie du microscope, un niveau de signal et une vitesse d'imagerie accrus, la réduction de la réflexion spéculaire détectée, et des procédés de fixation sur un biomicroscope de lampe à fente ou aux fins d'une utilisation portative.
PCT/US2025/013648 2024-01-30 2025-01-29 Dispositif ophtalmoscopique et procédé de capture d'images l'utilisant Pending WO2025165910A1 (fr)

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US20160000320A1 (en) * 2014-07-03 2016-01-07 Carl Zeiss Meditec, Inc. Systems and methods for spectrally dispersed illumination optical coherence tomography
US20170105615A1 (en) * 2015-10-16 2017-04-20 Ricoh Company, Ltd. Construction of an Individual Eye Model Using a Plenoptic Camera
US20200400422A1 (en) * 2019-06-21 2020-12-24 Tesseract Health, Inc. Optical coherence tomography eye imaging techniques
US20220257111A1 (en) * 2019-08-01 2022-08-18 Carl Zeiss Meditec, Inc. Ophthalmic imaging with k-mirror scanning, efficient interferometry, and pupil alignment through spatial frequency analysis

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100056928A1 (en) * 2008-08-10 2010-03-04 Karel Zuzak Digital light processing hyperspectral imaging apparatus
US20110273668A1 (en) * 2008-12-26 2011-11-10 Canon Kabushiki Kaisha Optical tomographic imaging apparatus and imaging method for an optical tomographic image
US20160000320A1 (en) * 2014-07-03 2016-01-07 Carl Zeiss Meditec, Inc. Systems and methods for spectrally dispersed illumination optical coherence tomography
US20170105615A1 (en) * 2015-10-16 2017-04-20 Ricoh Company, Ltd. Construction of an Individual Eye Model Using a Plenoptic Camera
US20200400422A1 (en) * 2019-06-21 2020-12-24 Tesseract Health, Inc. Optical coherence tomography eye imaging techniques
US20220257111A1 (en) * 2019-08-01 2022-08-18 Carl Zeiss Meditec, Inc. Ophthalmic imaging with k-mirror scanning, efficient interferometry, and pupil alignment through spatial frequency analysis

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