Ophthalmic system and method for a clinical device using epi-illumination with a plurality of point light sources

Abstract

An ophthalmic illumination and imaging system with transscleral / transpalpebral illumination of the fundus includes a light delivery device including multiple light-emitting regions, each of which is independently controllable and configured to be directed toward the sclera of a subject's eye for measurement to provide oblique transscleral illumination of the fundus; an active ocular aberration correction system; and an imaging system configured to create multiple images of the fundus on multiple imaging sensors.

Description

Technical Field

[0001] The present invention relates to oblique transscleral illumination of the retina by light sources at several (physical points) around the eye, enabling dark field imaging, high resolution imaging, large field imaging and retinal tracking.

Background Art

[0002] We have described in Patent Document 1 a method of transscleral illumination enabling dark field and a phase gradient technique using the scattering characteristics of the fundus.

[0003] Current ophthalmic devices based on OCT, OCT angiography and SLO have tracking systems implemented by a scanned beam that is adjusted. A retinal tracking system, as described in the context of ophthalmic instruments, consists of a method of monitoring the retina and measuring its displacement, combined with a method of keeping the retinal imaging zone active even when the eye is moving. These systems generally allow the operator to actively direct the imaging zone to any location (within given limits) selected for imaging, even when the patient is unable to fixate on the target.

[0004] An SLO system linked to a tracking system and adaptive optics is described in Patent Document 2, where a first module tracks a reference feature in the eye and a second module controls the light beam to move the imaging beam relative to the reference feature. A related publication for the same system is Non-Patent Document 1. This includes a large field imaging function (on the retina, >25°). Furthermore, a competing method of retinal tracking at 960 Hz is shown in Non-Patent Document 2.

[0005] Retinal tracking is further implemented in OCT and OCT angiography systems as described in Patent Document 3, Patent Document 4 and Patent Document 5. OCT devices linked to eye tracking are detailed in Patent Document 6 or Patent Document 7.

[0006] More recently, the OCT technique has been coupled to both a SLO system with a large field of view and a compensation optical system. An AO-OCT system incorporating retinal tracking is shown, for example, in Non-Patent Document 3. A system including OCT, SLO, and retinal tracking is detailed in Patent Document 8.

[0007] The method shown in Patent Document 9 is a multi-scale device having several illumination modules coupled to a scanning system. In this invention, the scanning system is performed by either an SLO or an OCT method including a compensation optical system.

[0008] The principle described in Non-Patent Document 4 uses information from pupil displacement to correct for eye aberrations by a compensation optical system. This includes a camera-based system that tracks the pupil position.

[0009] Fundus camera systems using trans-scleral illumination or trans-eyelid illumination have been developed. Patent Document 10 describes different devices, shapes, and wide-field trans-scleral or trans-eyelid systems using scleral / skin tissue for a light projection system. Further, Patent Document 11 shows a fundus imaging system by projecting a beam onto the sclera. Further, Annidis has a commercial device, Patent Document 12, using trans-scleral illumination for imaging the choroid. In 2017, Lingenfelder et al. showed a trans-scleral illumination system using LEDs, Non-Patent Document 5.

[0010] Finally, the patent of Patent Document 13 describes a device incorporating a retinal tracking system used for determining the user's gaze direction on a microdisplay.

[0011] The contrast of a phase object can be enhanced by performing filtering in the Fourier plane (or pupil plane). The principle has been demonstrated in microscopy in the following publications: Non-Patent Document 6, Non-Patent Document 7; Non-Patent Document 8 and Non-Patent Document 9.

[0012] The trans-scleral method is described using one illumination point, or optionally two illumination points where two point light sources provide illumination simultaneously or non-simultaneously. Here, a point means "point-like", such as a small area. This means any propagation of a light beam that illuminates a specific part of the eye / eyelid or the entire eye / eyelid.

[0013] None of the above systems provide a system that uses trans-scleral illumination to simultaneously provide a high-resolution - corrected compensation optics - image and a large field of view for the execution of retinal tracking.

[0014] None of the above inventions use a retinal imaging system (full field of view) connected to a compensation optics based on a tracking system implemented in a multi-pixel sensor camera.

Prior Art Documents

Patent Documents

[0015]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Non-Patent Literature

[0016]

Non-Patent Literature 1

Non-Patent Literature 2

Non-Patent Literature 3

Non-Patent Literature 4

Non-Patent Literature 5

Non-Patent Literature 6

Non-Patent Literature 7

Non - Patent Document 8

Non - Patent Document 9

Summary of the Invention

Means for Solving the Problems

[0017] The present invention provides an ophthalmic illumination and imaging system by trans - scleral / trans - eyelid illumination of the fundus. The system includes a light - delivering device including a plurality of light - emitting regions; each light - emitting region is independently controllable and configured to be directed towards the sclera of the subject eye for measurement to provide trans - scleral oblique illumination of the fundus; an active eye aberration correction system; and an imaging system configured to create a plurality of images of the fundus on a plurality of imaging sensors.

[0018] In a preferred embodiment, the system further includes an active tracking system configured to track the movement of the fundus and spatially stabilize at least one of the plurality of images of the fundus.

[0019] In a more preferred embodiment, the tracking system includes a tracking sensor configured to measure the movement of the fundus and a tracking corrector configured to correct at least one of the plurality of images spatially stabilized with respect to the movement.

[0020] In a further preferred embodiment, the system further includes a sequential switch configured to sequentially turn on one of the plurality of light-emitting regions at a time and activate a corresponding sequence when a fundus image is created by the imaging system.

[0021] In a further preferred embodiment, the active eye aberration correction system includes a wavefront sensor and a wavefront corrector.

[0022] In a further preferred embodiment, the plurality of images are generated by a light delivery device.

[0023] In a further preferred embodiment, the measurement of eye movement is performed using at least one of the plurality of fundus images.

[0024] In a further preferred embodiment, the correction of eye movement is performed by tilting a mirror disposed on an optically conjugated eye pupil plane.

[0025] In a further preferred embodiment, the correction of eye movement is performed using the tiltable ability of a wavefront corrector used for active correction of eye aberration.

[0026] In a further preferred embodiment, the correction of eye movement is performed using two-axis tilting of an entire wavefront corrector by an external turntable.

[0027] In a further preferred embodiment, the correction of eye movement is performed using two-axis tilting of a mirror that is not a wavefront corrector.

[0028] In a further preferred embodiment, the plurality of imaging paths for creating the plurality of fundus images are separated by a beam splitter or a dichroic mirror.

[0029] In a further preferred embodiment, the light delivery device includes a light diffuser.

[0030] In a further preferred embodiment, the diffuser incorporated in the light delivery device is used to obtain a spot with a width of several millimeters on the sclera or the skin surface.

[0031] In a further preferred embodiment, the diffuser moves so as to bring about temporal averaging of the speckle noise.

[0032] In a further preferred embodiment, the wavelength of the light delivery device is selected to be about 400 nm to 1200 nm in the transmission range of the sclera-choroid-skin.

[0033] In a further preferred embodiment, the light delivery device includes a plurality of basic components such as a light emitting diode, a superluminescent diode, an organic light emitting diode, and an optical fiber.

[0034] In a further preferred embodiment, the individual light emitting regions have different temporal emission spectra from each other.

[0035] In a further preferred embodiment, the individual light emitting regions have different angular emission spectra from each other.

[0036] In a further preferred embodiment, the system further includes a camera configured to record the interference between one or more exiting beams from the pupil and an additional reference beam extracted from the light delivery device before entering the eye.

[0037] In a further preferred embodiment, the inhomogeneous phase or absorption object is disposed on the conjugate pupil plane so as to enhance the phase contrast.

[0038] The present invention will be better understood from the following detailed description with reference to the accompanying drawings. The contents of the drawings will be briefly described below.

Brief Description of the Drawings

[0039]

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Mode for Carrying Out the Invention

[0040] Overview The present invention relates to an ophthalmic system and method based on trans-scleral illumination connected to a compensation optical system and a retina tracking function. The system can include a retina camera that images the retina with a high resolution of digital sampling of less than 2 μm / pixel, and a retina camera that images the retina over a large field of view (typically greater than 30°) with digital sampling of 20 μm / pixel. In addition, the imaging system includes a compensation optical loop to correct for the aberrations of the eye. The compensation optical loop is implemented by, but not limited to, a Shack-Hartmann wavefront sensor and a deformable mirror. The wavefront sensor senses the aberration in real time and sends control feedback to the deformable mirror. The tracking system is implemented by a two-axis tiltable mirror (or tilting / tiltable platform) of the relay pupil plane of the imaging system with a large field of view image as feedback for the calculation of the tilt.

[0041] Instead of using the eye lens as part of the illumination path, different layers of the eye (retina, choroid, sclera, and skin) are used as a transmissive scattering layer for illumination. The following methods are shown as embodiments: · Light passes through the skin layer, sclera, choroid, and retina near the eye. The transmitted and scattered light illuminates the fundus. No light enters the pupil-lens. The light delivery device is non-contact. · The optical device that sends the propagating light beam (hereinafter referred to as "beam") to the sclera or skin is designed to create a focal spot or an optically surfaced shape with any defined boundary (hereinafter referred to as "spot") on the sclera or skin, and the spot diameter is several millimeters. · The optical device that sends the beam to the sclera or skin is designed to include a diffusing element that reduces the spatial coherence of the light source, and the diffuser moves to average the temporal speckle pattern of the sensor. · The retina tracking system acts as a closed loop with a large field of view (hereinafter referred to as "FOV") image that functions as feedback. The large FOV camera is a tracking sensor. · The retinal tracking system is implemented by a two-axis tilt actuator with a light reflecting surface (hereinafter referred to as "mirror") attached thereto and is disposed on an optically conjugate pupil plane. The mirror disposed on the tilt actuator is a tracking corrector. · The conjugate pupil plane used for performing retinal tracking is a correction plane of a compensation optical loop. · The compensation optical system and the retinal tracking loop are connected. · A large FOV image is simultaneously obtained by the same epi-illumination as the high-resolution image. · The imaging optical path is split such that most of the power goes towards the high-resolution path in order to maintain a good SNR in the high-resolution image while having a good contrast in the large FOV image. The power ratio between the large FOV beam and the high-resolution beam is not limited, but is 4% for the large FOV and 96% for the high-resolution. · The phase contrast image of the transparent layer of the retina is enhanced by a phase or absorption pattern inserted into the pupil plane. · Detection is performed at the sensor by causing interference between one or more epi-illumination sources and a reference beam. · The optical section in the photoreceptor / RPE layer is brought about by a combination of illumination through the pupil / epi-illumination. · The epi-illumination beam is shaped to maximize optical transparency through the eye tissue.

[0042] Illumination is provided by, but not limited to, a single light source or a combination of light sources in the range of 400 - 1200 nm. Such light sources include, but are not limited to: light emitting diodes, organic light emitting diodes, superluminescent light emitting diodes, quantum dot light sources, lamps, blackbody radiation sources, side emitting fibers, front emitting fibers including elements that direct light towards the skin. Different light sources in the same delivery device can provide the same or different illumination spectra.

[0043] Illumination method and apparatus Configuration 1 Referring to FIG. 1, the illumination beam 100 is provided by a laser diode connected to a multimode fiber 101. The output of the multimode fiber 101 illuminates a light diffuser 102 (scattering plate) to cover a disc with a diameter of d0 on the light diffuser 102. The extended light source generated by the disc with a diameter of d0 emits a beam, and the beam is collimated by the first lens L1. The second lens L2 forms an image with a corresponding diameter of d1 on the skin of the dielectric film 103 or the disc with a diameter of d0.

[0044] Referring to FIG. 2, the diffuser can be attached to a movable plate 200 actuated by a vibrator 201 so as to average the speckle particles generated by the spatially coherent light of the laser diode. The vibrator 201 moves the speckle pattern faster than the integration time of an imaging camera (not shown in FIG. 2). The figure shows an example of a design integrated with a 1-inch lens.

[0045] Configuration 2 Referring to FIG. 3, the system that projects light onto the dielectric film 103 is a light-emitting diode (LED) (not shown in the drawing). The LED device generates an extended light source in the shape of a square with a side length of x0, which is collimated by the first lens L1, and an image is formed on the dielectric film 103 or the skin by the lens L2. The image of the LED is a square with a side length of x1.

[0046] Imaging device Configuration 1 Referring to FIG. 4, large field of view (FOV) and small field of view images are simultaneously generated by two separate imaging paths. The separation is achieved by placing a sliding optical element that uses a small portion x0 of the total light beam to obtain a large field of view image.

[0047] Configuration 2 Referring to FIG. 5, the image after trans-scleral illumination is obtained by superimposing a reference beam 500 on a beam 501 emerging from the eye / retina 103. The final image is extracted from the interference.

[0048] Configuration 3 Referring to FIG. 6, the figure serves to illustrate that the tracking system is implemented according to the flowchart of the presentation. A set of images is acquired, and then the images are aligned. The average value calculated from this set is used as a future reference. In the next step, the movement and rotation are calculated. Next, corrections are applied to the tiled images and the images are recorded. The large field of view imaging system provides feedback to the tracking corrector / actuator. When blinks or pupil lost occur, the tracking loop is performed.

[0049] Referring to FIG. 7, this includes a schematic diagram of the tracking actuator or corrector. The actuator is arranged on the conjugate pupil plane and is configured to generate tilts along two orthogonal directions.

[0050] Configuration 4 Referring to FIG. 8, it shows an optical arrangement combining wavefront correction and retinal tracking. The wavefront correction closed loop is composed of a wavefront sensor (WFS) and a wavefront corrector (WFC). Retinal tracking is composed of a large field of view acquisition device used as a tracking sensor (TS) and a tracking corrector (TC). In this example, the tracking corrector and the wavefront corrector are incorporated into a single device that can be a deformable mirror, a spatial light modulator.

[0051] Alternatively, the WFS sensor can also directly measure the tilt to perform retinal tracking.

[0052] Referring to FIG. 9, the figure shows a layout example according to the present invention. After being illuminated by epi-scleral illumination, the retina R is imaged through the pupil P of the eye. The system consists of two different scale imaging paths ending with a large FOV camera and a high-resolution camera. The wavefront aberration correction system consists of a Shack-Hartmann wavefront sensor and a deformable mirror wavefront corrector. The retina tracking system consists of a large FOV camera functioning as a tracking sensor and a deformable mirror functioning as a tracking corrector. The deformable mirror generates the tilt used for tracking correction by using the deformation of its reflective film and / or by being disposed on the upper surface of a two-axis turntable.

[0053] Referring to FIG. 10, the figure shows another layout example according to the present invention. This description is the same as that of FIG. 9 except for the retina tracking corrector. In this example, the movable mirror functions as a tracking corrector, but this mirror is not a wavefront corrector used in the wavefront aberration correction system. The movable mirror is disposed on the conjugate pupil plane and consists of a normal planar mirror disposed on a two-axis turntable.

[0054] Configuration 5 Referring to FIG. 11, the figure shows an example of a phase / absorption pattern in the Fourier / pupil plane for performing beam filtering. Three examples of the pattern are given: dark field, central phase contrast, and spiral phase contrast. The diffracted beam will be filtered to obtain a high-contrast image of a phase object such as the transparent cells of the retina.

[0055] The technical background of the present invention includes the prior art described herein, as well as technical fields such as epi-scleral illumination, phase contrast imaging, dark field retina imaging, and quantitative phase contrast microscopy, retina tracking, large / small FOV, etc.

[0056] The following are some references to ophthalmic devices using epi-scleral illumination: - WO2017195163Al, System, method and apparatus for retinal absorption phase and dark field imaging with oblique illumination. - US Patent No. 7387385B2, SURGICAL MICROSCOPE - US Patent Application Publication No. 2007 / 0159600Al, TRANSCLERAL OPTHALMIC ILLUMINATION METHOD AND SYSTEM - US Patent Application Publication No. 20070030448Al, ILLUMINATION UNIT FOR FUNDUS CAMERAS AND / OR OPHTHALMOSCOPES - A. Schalenbourg, L. Zografos "Pitfalls in colour photography of choroidal tumours." Eye. 2013;27(2):224 - 229 pages - Devrim Toslak, Damber Thapa, Yanjun Chen, Muhammet Kazim, Erol, R.V.Paul Chan, and Xincheng Yao, "Trans - palpebral illumination: an approach for wide - angle fundus photography without the need for pupil dilation," Opt. Lett. 41, 2688 - 2691 pages (2016).

[0057] Prior literature on dark - field imaging in ophthalmology: - D. Scoles, Y.N. Sulai and A. Dubra "In vivo dark - field imaging of the retinal pigment epithelium cell mosaic," Biomed. Opt. Exp. 4, 9, 1710 - 1723 pages (2013) - T.Y.P. Chui, D.A.VanNasdale, and S.A. Burns, "The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope," Biomed. Opt. Exp. 3, 10, pp. 2537 - 2549 (2012) - T.Y.P. Chui, T.J. Gast, and S.A. Burns, "Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy," Invest Ophthalmol VisSci. 54, pp. 7115 - 7124 (2013).

[0058] Prior literature on retinal tracking: - Patent Document 3 - Patent Document 4 - Patent Document 5 - Patent Document 6 - Patent Document 7 - Non - Patent Document 3 - Patent Document 2 - Non - Patent Document 1 - Non - Patent Document 2 - Patent Document 13

[0059] Prior literature on multi - scale retinal imaging: - Patent Document 8 - Patent Document 9

[0060] Prior literature on Fourier filtering for phase imaging: - Non - Patent Document 6 - Non - Patent Document 7; Non - Patent Document 8 - Non - Patent Document 9

[0061] Application The application of the system is to the retinal layer between the inner limiting membrane and the outer limiting membrane above the photoreceptor, that is: - ILM - Inner limiting membrane - RNFL - Retinal nerve fiber layer - GCL - Ganglion cell layer - IPL - Inner plexiform layer - INL - Inner nuclear layer - OPL - Outer plexiform layer - ONL - Outer nuclear layer - ELM - Outer limiting membrane Examples include quantitative phase imaging of the following:

[0062] Next, the proposed system can be used to provide dark field images or absorption - contrast images of the choroid and RPE (retinal pigment epithelium), and can image choroidal tumors and the microvasculature of the choroid with enhanced contrast.

[0063] The proposed system can image transparent cells by phase contrast in any of the above - mentioned layers.

[0064] Retinal tracking enables long - term patient follow - up, and thus validates the clinical application of the device.

Claims

**Claim 1** An ophthalmic imaging system by trans-scleral illumination of the fundus, comprising: A light delivery device including a plurality of light emitting regions; each light emitting region is independently controllable and is configured to be directed towards the sclera of the eye to be measured to provide trans-scleral oblique illumination of the fundus; a light delivery device; An active eye aberration correction system And including; Further including an imaging system configured to create a plurality of images of the fundus on a plurality of imaging sensors, wherein the plurality of imaging sensors include a retinal camera configured to image the retina of the eye to be measured with high resolution and another retinal camera configured to image the retina over a large field of view of at least about 30°; Further including an active tracking system configured to track the movement of the fundus and configured to spatially stabilize at least one of the plurality of images of the fundus; The measurement of eye movement is performed using at least one of the plurality of fundus images; The correction of eye movement is performed using a two-axis tipping / tilt platform that supports a full wavefront corrector by an external turntable, or The correction of eye movement is performed using a two-axis tipping / tilt platform that supports a mirror other than a wavefront corrector; The ophthalmic imaging system. **Claim 2** The system according to claim 1, wherein the retinal camera is configured to image the retina with a digital sampling smaller than 2 μm / pixel. **Claim 3** The system according to claim 1 or 2, wherein the retinal camera is configured to image the retina with a digital sampling of 20 μm / pixel. **Claim 4** The system according to any one of claims 1 to 3, wherein the imaging system is configured to simultaneously create a plurality of images of the fundus on a plurality of imaging sensors. **Claim 5** The system according to claim 1, wherein the tracking system includes a tracking sensor for measuring the movement of the fundus and a tracking corrector configured to correct one of the plurality of spatially stabilized images for the movement. **Claim 6** The system according to claim 1, further including a sequential switch configured to sequentially turn on one of the plurality of light emitting regions at a time when a fundus image is created by the imaging system and to activate a corresponding sequence. **Claim 7** The active eye aberration correction system is the system according to claim 1, including a wavefront sensor and a wavefront corrector.

8. The system according to claim 1, wherein the plurality of images are generated by a light delivery device.

9. The system according to claim 1, wherein the correction of eye movement is performed by tilting a mirror disposed on an optically conjugate eye pupil plane.

10. The system according to claim 1, wherein the correction of eye movement is performed using the tiltable ability of a wavefront corrector used for active correction of eye aberration.

11. The system according to claim 1, wherein a plurality of imaging paths for creating a plurality of fundus images are separated by a beam splitter or a dichroic mirror.

12. The system according to claim 1, wherein the light delivery device includes a light diffuser.

13. The system according to claim 12, wherein the diffuser incorporated in the light delivery device is used to obtain a spot with a width of several millimeters on the sclera or the skin surface.

14. The system according to claim 12, wherein the diffuser moves so as to bring about temporal averaging of speckle noise.

15. The system according to claim 1, wherein the wavelength of the light delivery device is selected to be about 400 nm to 1200 nm in the transmission range of the sclera - choroid - skin.

16. The system according to claim 1, wherein the light delivery device includes a plurality of basic components selected from the group consisting of light emitting diodes, superluminescent diodes, organic light emitting diodes, and optical fibers.

17. The system according to claim 15, wherein the individual light emitting regions have different temporal emission spectra from each other.

18. The system according to claim 15, wherein the individual light emitting regions have different angular emission spectra from each other.

19. The system according to claim 1, further including a camera configured to record interference between one or more exiting beams from the pupil and an additional reference beam extracted from the light delivery device before entering the eye.

Images