WO2018016409A1 - Dispositif et procédé d'analyse de globe oculaire - Google Patents

Dispositif et procédé d'analyse de globe oculaire Download PDF

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Publication number
WO2018016409A1
WO2018016409A1 PCT/JP2017/025508 JP2017025508W WO2018016409A1 WO 2018016409 A1 WO2018016409 A1 WO 2018016409A1 JP 2017025508 W JP2017025508 W JP 2017025508W WO 2018016409 A1 WO2018016409 A1 WO 2018016409A1
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WO
WIPO (PCT)
Prior art keywords
light
eyeball
emitted
wavelength
irradiated
Prior art date
Application number
PCT/JP2017/025508
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English (en)
Japanese (ja)
Inventor
小出　珠貴
優二 池田
Original Assignee
株式会社アサヒビジョン
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Priority to JP2017566440A priority Critical patent/JP6392999B2/ja
Publication of WO2018016409A1 publication Critical patent/WO2018016409A1/fr

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    • 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
    • A61B3/12—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
    • 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
    • A61B3/14—Arrangements specially adapted for eye photography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/19—Dichroism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration

Definitions

  • the present invention relates to an eyeball analyzing apparatus and an eyeball analyzing method.
  • Patent Document 1 An apparatus that non-invasively measures an eyeball by an optical method has been conventionally proposed (for example, Patent Document 1).
  • an object of the present invention is to provide an eyeball analysis apparatus and an eyeball analysis method that can detect a minute change in the state of the eyeball and are useful for early detection of a disease or the like.
  • an eyeball analyzing apparatus of the present invention includes a light irradiating means, a light separating means, and a spectroscopic means, wherein the light separating means includes an imaging means, and the spectroscopic means includes a wavelength variable filter.
  • the light irradiating means irradiates the eyeball with light
  • the wavelength tunable filter divides the emitted light emitted from the eyeball irradiated with the light
  • the imaging means divides the emitted light.
  • the dispersed light is two-dimensionally separated according to the position of the space of the eyeball by the imaged pixels on the image obtained by imaging.
  • the eyeball analysis method of the present invention includes an irradiation step of irradiating light to an eyeball, a spectroscopic step of splitting outgoing light emitted from the irradiated eyeball, and outgoing light emitted from the irradiated eyeball.
  • a light separation step of separating the light according to the position of the space, and in the spectroscopic step, the output light is dispersed by a wavelength tunable filter, and in the light separation step, the dispersed light is imaged.
  • the dispersed outgoing light is two-dimensionally separated by pixels on the image obtained by imaging.
  • an eyeball analysis apparatus and an eyeball analysis method that can detect minute changes in the state of the eyeball and are useful for early detection of diseases and the like.
  • FIG. 1 is a diagram showing an example of the configuration of an eyeball analyzer of the present invention.
  • FIG. 2 is a diagram showing another example of the configuration of the eyeball analyzer of the present invention.
  • FIG. 3 is a diagram showing still another example of the configuration of the eyeball analyzer of the present invention.
  • FIG. 4 is a schematic diagram showing the concept of three-dimensional spectroscopic analysis in which the wavelength is changed.
  • the light applied to the eyeball may be, for example, monochromatic light or, for example, mixed light including light having a plurality of wavelengths, for example, continuous light, monochromatic light, or a mixed light thereof. It may be.
  • the monochromatic light may be laser light, for example.
  • the laser beam may be, for example, a pulse laser beam or a CW (continuous oscillation) laser beam.
  • the mixed light including the light of the plurality of wavelengths may be, for example, continuous light or a mixed light of a plurality of monochromatic lights.
  • the continuous light may be, for example, white light or super continuum (SC) light.
  • the spectroscopic means may further include a narrow band filter, and the split outgoing light may pass through the narrow band filter.
  • the eyeball analyzer of the present invention may further include, for example, a circular polarization unit, and the light incident on the eyeball may be circularly polarized by the circular polarization unit.
  • the eyeball analyzer of the present invention further includes a circularly polarized light analyzing means, and the circularly polarized light analyzing means causes a difference in absorbance with respect to left and right circularly polarized light (dichroism) in at least a part of the eyeball. May be detected.
  • the eyeball analyzer of the present invention may further include, for example, linearly polarizing means, and the outgoing light emitted from the eyeball irradiated with the continuous light may be linearly polarized by the linearly polarizing means.
  • the eyeball analyzer of the present invention further includes linearly polarized light analyzing means, and the linearly polarized light is analyzed by the linearly polarized light analyzing means, whereby left and right circularly polarized light in at least a part of the eyeball. A difference in refractive index with respect to (optical rotation) may be detected.
  • the spectroscopy by the spectroscopic means is not particularly limited.
  • the emitted light is Raman scattered light, it is Raman spectroscopy.
  • analysis may be quantitative analysis (measurement) or qualitative analysis unless otherwise specified.
  • FIG. 1 shows an example of the configuration of the eyeball analyzer of the present invention.
  • this eyeball analyzing apparatus includes a light irradiating means 10 for irradiating the eyeball with continuous light, and a light separation and spectroscopic unit (hereinafter simply referred to as “unit”) 100.
  • the light irradiation means 10 includes a light source 10A, a lens 11, a beam splitter 12, and a lens 13.
  • a white light source for example, a super continuum (hereinafter sometimes referred to as “SC”) light source, an LED (light emitting diode), or the like can be used.
  • SC super continuum
  • the beam splitter is not particularly limited, but may be, for example, a beam splitter having polarization separation ability, or a half mirror having no polarization separation ability when polarization separation ability is not required.
  • the unit 100 separates the outgoing light emitted from the eyeball 1 irradiated with the continuous light according to the position of the space of the eyeball 1 and the light separating means (imaging means) 20 and separates the outgoing light for each wavelength.
  • Unit 100 further includes lenses 22 and 41. The components of the unit 100 are arranged in the order of the lens 22, the spectroscopic means (wavelength variable filter) 31, the lens 41, and the light separation means (imaging means) 20 from the exit side of the light emitted from the eyeball 1 as illustrated. ing.
  • the wavelength variable filter (tunable filter) 31 may be, for example, a Fabry-Perot etalon.
  • the lens 41 may be a collimator lens, for example.
  • the imaging unit 20 may include, for example, an imaging device that displays an image of light, and an image may be formed on the front surface of the imaging device.
  • the imaging unit 20 may be a camera, for example, and an image may be formed on the imaging surface.
  • the image forming surface of the image pickup means 20 is, for example, a camera lens or an infrared camera (for example, a black silicon element when the wavelength is 1.2 ⁇ m or less, an InGaAs element or an HgCdTe element when the wavelength is 0.7 to 1.8 ⁇ m, In the case of 1 to 5 ⁇ m, it may be an imaging surface of an InSb element or HgCdTe).
  • the eyeball 1 is irradiated with continuous light by the light irradiation means 10.
  • continuous light is emitted from the light source 10A.
  • the continuous light may be, for example, white light or super continuum (SC) light.
  • SC super continuum
  • the continuous light emitted from the light source 10 ⁇ / b> A is converged by the lens 11, then reflected by the beam splitter 12, further converged by the lens 13, and then applied to the eyeball 1.
  • the light can reach the lower layer than the fundus, so that the state of the space between the fundus and the lower layer can be analyzed as described later. .
  • Examples of the portion of the space between the fundus and the lower layer below the fundus that can be analyzed according to the present invention include, for example, the fundus, the retina, the tomographic space between the fundus and the fundus, and the space. Blood vessels to be used.
  • the light irradiated to the eyeball 1 is mainly continuous light
  • the light irradiated on the eyeball is not limited to continuous light as described above.
  • the continuous light irradiated on the eyeball 1 is emitted from the eyeball 1 by reflection, fluorescence, scattering, or the like by the eyeball 1.
  • the outgoing light emitted from the eyeball 1 is converged by the lens 13 and passes through the beam splitter 12.
  • At least a partial image (for example, a fundus image) of the eyeball 1 is formed on the image plane 21 on the light incident side of the lens 22 by the emitted light transmitted through the beam splitter 12. Further, the emitted light is incident on the lens 22 from the image plane 21, collimated by the lens 22, and then dispersed by the wavelength tunable filter 31, thereby taking out monochromatic light having a specific wavelength. The extracted monochromatic light is converged by the lens 41 and irradiated to the imaging means 20. Then, the imaged means 20 images the dispersed outgoing light, and the dispersed outgoing light is two-dimensionally separated by pixels on the image obtained by imaging.
  • a partial image for example, a fundus image
  • the light separating means 20 can separate the emitted light emitted from the eyeball 1 two-dimensionally according to the position of the space of the eyeball 1.
  • the image is supplied to, for example, spectrum analysis means (not shown), and the spectrum of each visual field is analyzed. Thereby, a minute change in the state of the eyeball 1 can also be detected. Further, by changing the wavelength of the monochromatic light extracted by the wavelength tunable filter 31, analysis with light of different wavelengths is possible.
  • the eyeball analyzer of FIG. 1 has the advantage of high spatial resolution, for example. For this reason, the eyeball analyzer of FIG. 1 is useful for analysis using infrared light, for example.
  • the use of the eyeball analyzer of the present invention is not limited to this, and can be used for, for example, analysis using visible light.
  • the field of analysis may be expanded by scanning using a scanning mechanism (not shown) as necessary.
  • the wavelength of continuous light irradiated to the eyeball 1 is not particularly limited, but is, for example, 1000 to 1550 nm.
  • the wavelength does not exceed 1400 nm from the viewpoint of facilitating the light to reach the region to be analyzed in consideration of the absorption band of water in the eyeball.
  • the output of the light source should not exceed the maximum permissible exposure (MPE) specified in, for example, standardization of laser safety (JISC6802) and protection from optical hazards in optical optics (JIST15004-2). It is preferable to make it.
  • MPE maximum permissible exposure
  • JISC6802 standardization of laser safety
  • JIST15004-2 protection from optical hazards in optical optics
  • the exposure amount of the first light source the exposure amount of the second light source
  • the exposure amount of the light irradiated to the eyeball instead of the light emitted from the light source
  • the maximum allowable exposure amount may not be exceeded.
  • E1 Exposure amount E1 max of light emitted from the first light source: Maximum allowable exposure amount E2 at the wavelength of light emitted from the first light source
  • E2 Exposure amount E2 max of light emitted from the second light source Emission of the second light source Maximum allowable exposure at the wavelength of the incident light
  • FIG. 2 shows still another example of the configuration of the eyeball analyzer of the present invention.
  • the spectroscopic means is composed of only the wavelength tunable filter 31, but the apparatus of FIG. 2 further includes a narrow band filter 32 as shown in the figure. Means 30 are configured.
  • the narrow band filter 32 may be any other filter instead of the narrow band filter, for example, a wide band filter or an order cut filter.
  • the narrow band filter 32 is disposed between the wavelength tunable filter 31 and the lens 41 in FIG. Of the emitted light that has passed through the wavelength tunable filter 31, only light in the necessary wavelength band selectively passes through the narrowband filter 32 and is irradiated onto the lens 41. Except for these, the eyeball analysis apparatus of FIG.
  • the arrangement position of the narrow band filter 32 is not limited to the position of FIG. 2.
  • the narrow band filter 32 only needs to be able to make the emission light transmitted through the wavelength tunable filter 23 incident on the narrow band filter 32. It may be between the lens 41 and the imaging means 20.
  • the narrow band filter 32 blocks (cuts) unnecessary wavelength band light (light having a wavelength different from the detection target wavelength or light of other orders) included in the emitted light transmitted through the wavelength tunable filter 23. As described above, only light in a necessary wavelength band can be selectively transmitted.
  • FIG. 3 shows still another example of the configuration of the eyeball analyzer of the present invention.
  • a polarizing plate 61 is disposed between the lens 11 and the beam splitter 12 in the light irradiation means 10.
  • the half-wave plate 23 and the polarizing plate 24 are disposed in this order from the light emitting side between the lens 22 and the wavelength tunable filter 31.
  • the polarizing plate 24 may be a polarizing beam splitter instead of the polarizing plate, for example. Except for these, the eyeball analysis apparatus of FIG. 3 is the same as the eyeball analysis apparatus of FIG.
  • continuous light is emitted from the light source 10A.
  • the continuous light emitted from the light source 10 ⁇ / b> A is converged by the lens 11 and then converted into linearly polarized light by the polarizing plate 61.
  • the polarized continuous light is processed by the beam splitter 12 and the lens 13 in the same manner as in FIG. 1 and irradiated to the eyeball 1. Further, at least a part of the polarized light becomes emitted light from the eyeball 1 and becomes the lens 13 and the beam. Passes through the splitter 12.
  • the emitted light that has passed through the beam splitter 12 is processed by the unit 100 as follows. That is, first, the emitted light is processed in the same manner as in FIG. 1 by the image plane 21 and the lens 22 of the light separating means 20 and separated according to the position of the space of the eyeball 1. Next, the emitted light that has passed through the lens 22 enters the half-wave plate 23.
  • the half-wave plate 23 can be rotated, whereby the direction of linearly polarized light of the emitted light can be changed.
  • the emitted light that has passed through the half-wave plate 23 is selectively emitted as a linearly polarized light in a specific direction by the polarizing plate 24, and then separated for each wavelength by the wavelength tunable filter 31. Light is extracted.
  • the extracted monochromatic light is processed in the same manner as in FIG. 1 by the lens 41, the imaging means 20, and optionally the spectrum analysis means (not shown). At this time, by comparing spectral spectra of linearly polarized light in different directions by the spectrum analyzing unit, a difference in refractive index (optical rotation) with respect to left and right circularly polarized light in at least a part of the eyeball 1 may be detected.
  • the arrangement and usage of the polarizing plate are not limited to the example of FIG.
  • a circularly polarizing plate may be used instead of the linearly polarizing plate, and the light incident on the eyeball 1 or the light emitted (emitted) from the eyeball 1 may be circularly polarized.
  • the circularly polarizing plate for example, the half-wave plate 23 is replaced with a rotatable quarter-wave plate, or adjacent to the light incident side or the light exit side of the half-wave plate 23, A rotatable quarter wave plate may be used.
  • the circularly polarizing plate (circularly polarizing means) 61 may be capable of switching the left and right of the rotation direction of the circularly polarized light to be transmitted.
  • circularly polarized light can be converted into linearly polarized light by the quarter wavelength plate.
  • the half-wave plate 23 can change the direction of linearly polarized light or the direction of rotation of circularly polarized light.
  • a difference in absorbance with respect to left and right circularly polarized light in at least a part of the eyeball 1 can be detected.
  • optical isomers in the eyeball 1 can be detected. Examples of the optical isomers include L-forms and D-forms of amino acids or amino acid residues.
  • the eyeball analyzer and the eyeball analysis method of the present invention can be used for the following applications, for example. However, these are examples and do not limit the present invention.
  • a plane perpendicular to the direction of light incident on the eyeball can be analyzed in the eyeball according to the position of the eyeball space.
  • the surface to be analyzed is not particularly limited, but may be, for example, the fundus or at least a part of the retina, cornea, or lens.
  • FIG. 4 schematically shows the concept of three-dimensional spectroscopic analysis in the present invention.
  • FIG. 4 shows that, in addition to the plane direction (X direction and Y direction), an analysis corresponding to a change in wavelength (Z direction) is performed.
  • the “fundus tomography” includes a tomography of the space between the fundus and the lower layer than the fundus.
  • the direction parallel to the incident direction of light is three-dimensionally included. It is also possible to analyze. In addition to this, an analysis (four-dimensional spectroscopic analysis) in which the wavelength is further changed can be performed. For example, in addition to the four-dimensional spectroscopic analysis in which the wavelength is changed, five-dimensional spectroscopic analysis in which the measurement time is changed (time is added in the measurement direction) is also possible.
  • the relationship between the wavelength of the emitted light from the specific position and the polarization azimuth angle ( ⁇ ) of the emitted light is plotted two-dimensionally.
  • the state of the eyeball at the specific position can be analyzed.
  • the state of the eyeball include the degree of disease progression. More specifically, for example, the ratio of L-alginic acid and D-alginic acid at the specific position is calculated from the relationship between the wavelength at the specific position and the polarization azimuth angle ( ⁇ ). The degree of progression of cataract can be judged.
  • the degree of progression of the disease at the various positions can be determined.
  • the present invention can be used for the analysis of denatured proteins (such as crystallin) and substances secreted into the eyeball. Specifically, for example, it can be used for early detection of Alzheimer's disease by analyzing amyloid protein in the eyeball.
  • tryptophan in the lens-constituting protein is analyzed by analyzing oxidized kynurenine or 3-hydroxykynurenine, or by combining lysine residues in the protein and sugars in the body ( Analysis of advanced glycated end products) enables early detection of the above-mentioned cataracts.
  • the present invention can analyze the deep part of the fundus or the space between the fundus and the fundus by using light having a long wavelength with high transmission power.
  • Capillary state, retina state, etc. can be analyzed.
  • the eyeball can be analyzed non-invasively and simply.
  • the light applied to the eyeball is mixed light including light of a plurality of wavelengths (for example, white light, continuous light such as SC light, or mixed light of a plurality of monochromatic lights). It can be.
  • SS-OCT Swept Source Optical Coherence Tomography
  • multiple wavelengths of light are incident in time, which increases the measurement (analysis) time and increases the time required for the patient.
  • the burden also becomes large.
  • the eyeball can be analyzed only by irradiating the eyeball with the mixed light including the light of the plurality of wavelengths once. As a result, the analysis time can be greatly shortened compared to SS-OCT, and the burden on the patient can be reduced.
  • this description is merely an example and does not limit the present invention.
  • Embodiments 1 to 3 have described examples of the eyeball analysis apparatus and eyeball analysis method of the present invention, and further described examples of uses of the present invention. However, this invention is not limited to these, Arbitrary changes are possible. For example, Raman spectroscopy such as CARS can be used as the spectroscopy, but is not limited to this, and any commonly used spectroscopy can be used.
  • Raman spectroscopy such as CARS can be used as the spectroscopy, but is not limited to this, and any commonly used spectroscopy can be used.
  • the present invention it is possible to provide an eyeball analysis apparatus and an eyeball analysis method that can detect a minute change in the state of the eyeball and are useful for early detection of a disease or the like.
  • the present invention can greatly contribute to early detection of various diseases related to the state of the eyeball.

Abstract

L'invention a pour objet de fournir un dispositif et un procédé d'analyse de globe oculaire utiles pour la détection précoce de maladies, qui permettent de détecter même de très petites modifications de l'état du globe oculaire. Le dispositif d'analyse de globe oculaire de l'invention contient un moyen d'irradiation lumineuse (10), un moyen de séparation lumineuse et un moyen de spectroscopie. Ledit moyen de séparation lumineuse contient un moyen de prise de vue (20). Ledit moyen de spectroscopie contient un filtre variable en longueur d'onde (31). Ainsi, une lumière irradie le globe oculaire (1) à l'aide du moyen d'irradiation lumineuse (10), une lumière émise en sortie provenant du globe oculaire (1) irradié par ladite lumière, est soumise à une spectroscopie à l'aide du filtre variable en longueur d'onde (31), et ladite lumière émise en sortie soumise à la spectroscopie, est ensuite soumise à une prise de vue à l'aide du moyen de prise de vue (20), et est séparée en trois dimensions selon la position d'un espace dudit globe oculaire au moyen de pixels sur une image obtenue par la prise de vue.
PCT/JP2017/025508 2016-07-19 2017-07-13 Dispositif et procédé d'analyse de globe oculaire WO2018016409A1 (fr)

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Citations (5)

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Publication number Priority date Publication date Assignee Title
JP2009533160A (ja) * 2006-04-13 2009-09-17 ズッカーマン，ラルフ 定常状態の蛍光異方性を測定することで組織機能と代謝の非侵襲計測をする方法および装置
JP2009264787A (ja) * 2008-04-22 2009-11-12 Topcon Corp 光画像計測装置
JP2012508366A (ja) * 2008-11-04 2012-04-05 ウィリアム・マーシュ・ライス・ユニバーシティ 画像マッピング分光計
JP2013544589A (ja) * 2010-11-05 2013-12-19 フリーダム メディテック インコーポレイテッド 生体組織の構造的性質に影響する疾患を非侵襲的に検出するための装置および方法
JP2016107079A (ja) * 2014-11-26 2016-06-20 富士ゼロックス株式会社 眼球の光計測装置

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3014633B2 (ja) * 1995-11-16 2000-02-28 松下電器産業株式会社 尿検査方法
JP2017023328A (ja) * 2015-07-21 2017-02-02 富士ゼロックス株式会社 光学活性物質の濃度算出システム及びプログラム

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009533160A (ja) * 2006-04-13 2009-09-17 ズッカーマン，ラルフ 定常状態の蛍光異方性を測定することで組織機能と代謝の非侵襲計測をする方法および装置
JP2009264787A (ja) * 2008-04-22 2009-11-12 Topcon Corp 光画像計測装置
JP2012508366A (ja) * 2008-11-04 2012-04-05 ウィリアム・マーシュ・ライス・ユニバーシティ 画像マッピング分光計
JP2013544589A (ja) * 2010-11-05 2013-12-19 フリーダム メディテック インコーポレイテッド 生体組織の構造的性質に影響する疾患を非侵襲的に検出するための装置および方法
JP2016107079A (ja) * 2014-11-26 2016-06-20 富士ゼロックス株式会社 眼球の光計測装置

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