WO2018016409A1 - Eye analysis device and eye analysis method - Google Patents

Eye analysis device and eye analysis method 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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Prior art keywords
light
eyeball
emitted
wavelength
irradiated
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PCT/JP2017/025508
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French (fr)
Japanese (ja)
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小出　珠貴
優二 池田
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株式会社アサヒビジョン
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Priority to JP2017566440A priority Critical patent/JP6392999B2/en
Publication of WO2018016409A1 publication Critical patent/WO2018016409A1/en

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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

The purpose of the present invention is to provide an eye analysis device and eye analysis method which are capable of detecting small changes in the state of an eye, and are useful in the early detection of diseases or the like. This eye analysis device includes a photoirradiation means 10, a light separation means, and a spectroscopic means. The light separation means includes an imaging means 20. The spectroscopic means includes a wavelength-variable filter 31. The photoirradiation means 10 irradiates the eye 1 with light. The wavelength-variable filter 31 splits the emitted light which is emitted from the eye 1 irradiated with the light. The imaging means 20 captures an image of the split emitted light. Using the pixels on the image obtained by imaging, the split emitted light is two-dimensionally separated according to the spatial location thereof in the eye.

Description

眼球分析装置および眼球分析方法Eye analysis device and eye analysis method
　本発明は、眼球分析装置および眼球分析方法に関する。 The present invention relates to an eyeball analyzing apparatus and an eyeball analyzing method.
　光学的方法によって眼球を非侵襲的に測定する装置については、従来から提案されている（例えば、特許文献１等）。 An apparatus that non-invasively measures an eyeball by an optical method has been conventionally proposed (for example, Patent Document 1).
特開平５－２６１０６７号公報Japanese Patent Application Laid-Open No. 5-26167
　しかしながら、そのような装置では、例えば、眼球中のクリスタリンタンパク質の変性、眼球中の微量物質、網膜の微細な変化等を検出することはできなかったため、疾患の早期発見等が困難であった。 However, such an apparatus cannot detect, for example, degeneration of crystallin protein in the eyeball, trace substances in the eyeball, minute changes in the retina, and the like, making it difficult to detect diseases early.
　そこで、本発明は、眼球の状態の微細な変化も検出可能で、疾患の早期発見等に有用な眼球分析装置および眼球分析方法を提供することを目的とする。 Therefore, 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.
　前記目的を達成するために、本発明の眼球分析装置は、光照射手段、光分離手段、分光手段を含み、前記光分離手段が、撮像手段を含み、前記分光手段が、波長可変フィルターを含み、前記光照射手段により、光が眼球に照射され、前記波長可変フィルターにより、前記光を照射された前記眼球から出射する出射光が、分光され、前記撮像手段により、前記分光された出射光が撮像され、撮像して得られた画像上の画素によって、前記分光された出射光が、前記眼球の空間の位置に応じて二次元的に分離される。 In order to achieve the above object, 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, and 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.
　本発明の眼球分析方法は、眼球に光を照射する照射工程と、前記照射された眼球から出射する出射光を、分光する分光工程と、前記照射された眼球から出射する出射光を、前記眼球の空間の位置に応じて分離する光分離工程と、を含み、前記分光工程において、波長可変フィルターにより、前記出射光を分光し、前記光分離工程において、前記分光された出射光を撮像し、撮像して得られた画像上の画素によって前記分光された出射光を二次元的に分離する。 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.
　本発明によれば、眼球の状態の微細な変化も検出可能で、疾患の早期発見等に有用な眼球分析装置および眼球分析方法を提供することができる。 According to the present invention, it is possible to provide 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.
図１は、本発明の眼球分析装置の構成の一例を示す図である。FIG. 1 is a diagram showing an example of the configuration of an eyeball analyzer of the present invention. 図２は、本発明の眼球分析装置の構成の別の一例を示す図である。FIG. 2 is a diagram showing another example of the configuration of the eyeball analyzer of the present invention. 図３は、本発明の眼球分析装置の構成のさらに別の一例を示す図である。FIG. 3 is a diagram showing still another example of the configuration of the eyeball analyzer of the present invention. 図４は、波長を変化させた三次元分光分析の概念を示す模式図である。FIG. 4 is a schematic diagram showing the concept of three-dimensional spectroscopic analysis in which the wavelength is changed.
　つぎに、本発明について、例を挙げて説明する。ただし、本発明は、以下の説明により、なんら限定されない。 Next, the present invention will be described with examples. However, the present invention is not limited at all by the following description.
　本発明において、前記眼球に照射される光は、例えば、単色光でも、また、例えば、複数の波長の光を含む混合光であっても良く、例えば、連続光、単色光またはそれらの混合光であっても良い。前記単色光は、例えば、レーザー光であっても良い。前記レーザー光は、例えば、パルスレーザー光でも良いし、ＣＷ（連続発振）レーザー光でも良い。また、前記複数の波長の光を含む混合光は、例えば、連続光であってもよく、複数の単色光の混合光であってもよい。前記連続光は、例えば、白色光、またはスーパーコンティニューム（ＳＣ）光であっても良い。 In the present invention, 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. Further, 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.
　本発明の眼球分析装置は、例えば、前記分光手段が、さらに、狭帯域フィルターを含み、前記分光された出射光が前記狭帯域フィルターを通過しても良い。 In the eyeball analysis apparatus of the present invention, for example, the spectroscopic means may further include a narrow band filter, and the split outgoing light may pass through the narrow band filter.
　本発明の眼球分析装置は、例えば、さらに、円偏光手段を含み、前記円偏光手段により、前記眼球に入射する光が、円偏光されても良い。この場合、例えば、本発明の眼球分析装置が、さらに、円偏光分析手段を含み、前記円偏光分析手段により、前記眼球の少なくとも一部における、左右の円偏光に対する吸光度の違い（二色性）が検出されても良い。 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. In this case, for example, 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.
　本発明の眼球分析装置は、例えば、さらに、直線偏光手段を含み、前記直線偏光手段により、前記連続光を照射された前記眼球から出射する出射光が、直線偏光されても良い。この場合、例えば、本発明の眼球分析装置が、さらに、直線偏光分析手段を含み、前記直線偏光分析手段により前記直線偏光が分析されることで、前記眼球の少なくとも一部における、左右の円偏光に対する屈折率の違い（旋光性）が検出されても良い。 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. In this case, for example, 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.
　本発明において、前記分光手段による分光は特に制限されず、例えば、前記出射光がラマン散乱光であれば、ラマン分光である。 In the present invention, the spectroscopy by the spectroscopic means is not particularly limited. For example, if the emitted light is Raman scattered light, it is Raman spectroscopy.
　また、本発明において「分析」とは、特に断らない限り、定量分析（測定）でも良いし、定性分析でも良い。 In the present invention, “analysis” may be quantitative analysis (measurement) or qualitative analysis unless otherwise specified.
　以下、本発明の具体的な実施形態について説明する。ただし、以下の実施形態は例示であり、本発明は、これにより、なんら限定されない。 Hereinafter, specific embodiments of the present invention will be described. However, the following embodiment is an illustration and this invention is not limited at all by this.
［実施形態１］
　図１に、本発明の眼球分析装置の構成の一例を示す。図示のとおり、この眼球分析装置は、連続光を眼球に照射する光照射手段１０と、光分離および分光ユニット（以下、単に「ユニット」という。）１００とから構成されている。 [Embodiment 1]
FIG. 1 shows an example of the configuration of the eyeball analyzer of the present invention. As shown in the figure, 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.
　光照射手段１０は、光源１０Ａ、レンズ１１、ビームスプリッタ１２およびレンズ１３により構成されている。光源１０Ａとしては、例えば、白色光源、スーパーコンティニューム（以下「ＳＣ」ということがある。）光源、またはＬＥＤ（発光ダイオード）等を用いることができる。なお、本発明において、ビームスプリッタは、特に限定されないが、例えば、偏光分離能を有するビームスプリッタでも良いし、偏光分離能が必要ない場合は、偏光分離能を有しないハーフミラー等でも良い。 The light irradiation means 10 includes a light source 10A, a lens 11, a beam splitter 12, and a lens 13. As the light source 10A, for example, a white light source, a super continuum (hereinafter sometimes referred to as “SC”) light source, an LED (light emitting diode), or the like can be used. In the present invention, 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.
　ユニット１００は、前記連続光を照射された眼球１から出射する出射光を、眼球１の空間の位置に応じて分離する光分離手段（撮像手段）２０と、前記出射光を波長ごとに分光する分光手段（波長可変フィルター）３１とを含む。また、ユニット１００は、さらに、レンズ２２および４１を含む。ユニット１００の構成要素は、図示のとおり、眼球１からの出射光の出射側から、レンズ２２、分光手段（波長可変フィルター）３１、レンズ４１、光分離手段（撮像手段）２０の順序で配置されている。 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. Spectroscopic means (wavelength variable filter) 31. 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.
　波長可変フィルター（チューナブルフィルター）３１は、例えば、ファブリペローエタロン等であっても良い。 The wavelength variable filter (tunable filter) 31 may be, for example, a Fabry-Perot etalon.
　図１の眼球分析装置において、レンズ４１は、例えば、コリメータレンズであっても良い。 1, the lens 41 may be a collimator lens, for example.
　撮像手段２０は、例えば、光が像を表示する撮像素子を含んでも良く、その撮像素子の前面に画像が形成されても良い。撮像手段２０は、例えば、カメラであっても良く、その撮像面に画像が形成されても良い。図１において、撮像手段２０の画像形成面は、例えば、カメラレンズ、または赤外線カメラ（例えば、波長1.2μm以下の場合はブラックシリコン素子、波長0.7～1.8μmの場合はInGaAs素子やHgCdTe素子、波長1～5μmの場合はInSb素子またはHgCdTe）の撮像面であっても良い。 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. In FIG. 1, 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 μm or less, an InGaAs element or an HgCdTe element when the wavelength is 0.7 to 1.8 μm, In the case of 1 to 5 μm, it may be an imaging surface of an InSb element or HgCdTe).
　図１の眼球分析装置は、例えば、以下のようにして使用することができる。まず、光照射手段１０により、連続光が眼球１に照射される。具体的には、まず、光源１０Ａから連続光を照射される。前記連続光は、例えば、白色光、またはスーパーコンティニューム（ＳＣ）光であっても良い。光源１０Ａから照射された前記連続光は、レンズ１１によって収束され、つぎに、ビームスプリッタ１２によって反射され、さらに、レンズ１３によって収束された後に、眼球１に照射される。なお、眼球１の眼底に光が照射される場合は、前記光が眼底よりも下層にも届くことにより、後述するように、眼底および眼底よりも下層の間の空間の状態を分析可能である。本発明により分析可能な眼底および眼底よりも下層の間の空間の部位としては、例えば、後述するように、眼底、網膜、前記眼底および眼底よりも下層の間の空間の断層、前記空間に存在する血管等が挙げられる。また、本実施例および後述する他の実施例では、主に、眼球１に照射される光が連続光である場合について説明する。しかし、本発明において、眼球に照射される光（例えば、光源１０Ａから出射される光）は、前述のとおり、連続光に限定されない。 1 can be used as follows, for example. First, the eyeball 1 is irradiated with continuous light by the light irradiation means 10. Specifically, first, continuous light is emitted from the light source 10A. The continuous light may be, for example, white light or super continuum (SC) light. 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. In addition, when light is irradiated to the fundus of 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. In the present embodiment and other embodiments described later, the case where the light irradiated to the eyeball 1 is mainly continuous light will be described. However, in the present invention, the light irradiated on the eyeball (for example, light emitted from the light source 10A) is not limited to continuous light as described above.
　つぎに、眼球１に照射された前記連続光の少なくとも一部が、眼球１による反射、蛍光もしくは散乱等で、眼球１から出射される。眼球１から出射された出射光は、レンズ１３によって収束され、ビームスプリッタ１２を透過する。 Next, at least a part of 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.
　つぎに、ビームスプリッタ１２を透過した前記出射光により、レンズ２２の光入射側の像面２１に、眼球１の少なくとも一部の画像（例えば眼底像）が結像される。さらに、前記出射光は、像面２１からレンズ２２に入射し、レンズ２２によりコリメートされた後に、波長可変フィルター３１により分光され、特定波長の単色光が取り出される。取り出された単色光は、レンズ４１によって収束され、撮像手段２０に照射される。そして、撮像手段２０により、前記分光された出射光が撮像され、撮像して得られた画像上の画素によって前記分光された出射光が二次元的に分離される。このようにして、光分離手段２０により、眼球１から出射する出射光を、眼球１の空間の位置に応じて二次元的に分離することができる。その画像を、例えば、スペクトル解析手段（図示せず）に供し、各視野の分光スペクトルを解析する。これにより、眼球１の状態の微細な変化も検出可能である。また、波長可変フィルター３１により取り出される単色光の波長を変更することで、異なる波長の光による分析が可能である。 Next, 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. In this way, 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.
　図１の眼球分析装置によれば、例えば、空間分解能が高いという利点を有する。このため、図１の眼球分析装置は、例えば、赤外光を用いた分析に有用である。ただし、本発明の眼球分析装置の用途はこれに限定されず、例えば、可視光を用いた分析等にも使用できる。また、例えば、必要に応じ、スキャン機構（図示せず）を用いてスキャンすることにより、分析の視野を広げても良い。 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. However, 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. In addition, for example, the field of analysis may be expanded by scanning using a scanning mechanism (not shown) as necessary.
　なお、図１の装置において、眼球１に照射される連続光の波長は、特に限定されないが、例えば、１０００～１５５０ｎｍである。網膜、眼底等を分析する場合は、眼球中の水の吸収帯等を考慮して、分析対象部位まで光を届きやすくする観点から、波長が１４００ｎｍを超えないことが好ましい。 In the apparatus of FIG. 1, the wavelength of continuous light irradiated to the eyeball 1 is not particularly limited, but is, for example, 1000 to 1550 nm. When analyzing the retina, fundus, etc., it is preferable that 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.
　図１の装置に限らず、本発明の眼球分析装置において、眼球に照射される光の波長、出力等は、安全性を考慮して適切に選択することが好ましい。また、光源の出力は、例えば、レーザ安全性の標準化（JISC6802）および眼光学機器における光ハザードからの保護（JIST15004-2）等に定める最大許容露光量（MPE:Maximum　Permissible　Exposure）を超えないようにすることが好ましい。光源が複数の場合であって、それぞれの出射光の波長における最大許容露光量が同じ（同じ規制波長帯）場合は、全光源の出力の和が、最大許容露光量を超えないようにすることが好ましい。また、光源が２つの場合であって、それぞれの出射光の波長における最大許容露光量が異なる（異なる規制波長帯）場合は、第１の光源の露光量と、第２の光源の露光量とが、下記数式（１）の関係を満たすことが好ましい。光源が３つ以上の場合も、同様である。また、例えば、混合光が波長選択フィルターにより分光され、必要な波長の光のみが選択的に眼球に照射される場合は、光源からの出射光に代えて、眼球に照射される光の露光量が、最大許容露光量を超えないようにしても良い。
 
（Ｅ１／Ｅ１ｍａｘ）＋（Ｅ２／Ｅ２ｍａｘ）≦１　　　　　　（１）
 
Ｅ１：第１の光源の出射光の露光量
Ｅ１ｍａｘ：第１の光源の出射光の波長における最大許容露光量
Ｅ２：第２の光源の出射光の露光量
Ｅ２ｍａｘ：第２の光源の出射光の波長における最大許容露光量 In the eyeball analyzing apparatus of the present invention, not limited to the apparatus of FIG. 1, it is preferable to appropriately select the wavelength, output, and the like of the light irradiated to the eyeball in consideration of safety. Also, 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. When there are multiple light sources, and the maximum allowable exposure amount at the wavelength of each emitted light is the same (same regulatory wavelength band), the sum of the outputs of all light sources should not exceed the maximum allowable exposure amount Is preferred. Further, in the case where there are two light sources and the maximum allowable exposure amounts at different wavelengths of the emitted light are different (different regulated wavelength bands), the exposure amount of the first light source, the exposure amount of the second light source, However, it is preferable to satisfy | fill the relationship of following Numerical formula (1). The same applies when there are three or more light sources. In addition, for example, when the mixed light is spectrally separated by the wavelength selection filter and only the light of the necessary wavelength is selectively irradiated to the eyeball, the exposure amount of the light irradiated to the eyeball instead of the light emitted from the light source However, the maximum allowable exposure amount may not be exceeded.

(E1 / E1 max ) + (E2 / E2 max ) ≦ 1 (1)

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
［実施形態２］
　図２に、本発明の眼球分析装置の構成のさらに別の一例を示す。図１の装置は、分光手段が波長可変フィルター３１のみにより構成されていたが、図２の装置は、図示のとおり、さらに狭帯域フィルター３２を含み、波長可変フィルター３１および狭帯域フィルター３２により分光手段３０が構成される。なお、狭帯域フィルター３２は、狭帯域フィルターに代えて、他の任意のフィルターでも良く、例えば、広帯域フィルターでも良いし、オーダーカットフィルターでも良い。また、狭帯域フィルター３２は、図２では波長可変フィルター３１とレンズ４１との間に配置されている。波長可変フィルター３１を透過した前記出射光は、必要な波長帯域の光のみが選択的に狭帯域フィルター３２を透過し、レンズ４１に照射される。これら以外は、図２の眼球分析装置は、図１の眼球分析装置と同じである。また、狭帯域フィルター３２の配置位置は、図２の位置に限定されず、例えば、波長可変フィルター２３を透過した前記出射光を狭帯域フィルター３２に入射させることができれば良く、具体的には、レンズ４１と撮像手段２０との間等でも良い。狭帯域フィルター３２により、波長可変フィルター２３を透過した前記出射光に含まれる不要な波長帯域の光（検出対象の波長とは異なる波長の光、または他の次数の光）を遮断（カット）し、前記のとおり、必要な波長帯域の光のみを選択的に透過させることができる。 [Embodiment 2]
FIG. 2 shows still another example of the configuration of the eyeball analyzer of the present invention. In the apparatus of FIG. 1, 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. 2 is the same as the eyeball analysis apparatus of FIG. Further, the arrangement position of the narrow band filter 32 is not limited to the position of FIG. 2. For example, 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.
［実施形態３］
　図３に、本発明の眼球分析装置の構成のさらに別の一例を示す。図示のとおり、この眼球分析装置は、光照射手段１０において、レンズ１１とビームスプリッタ１２との間に、偏光板６１が配置されている。また、ユニット１００において、レンズ２２と波長可変フィルター３１との間に、１／２波長板２３および偏光板２４が、光出射側から前記順序で配置されている。なお、偏光板２４は、例えば、偏光板に代えて偏光ビームスプリッタであっても良い。これら以外は、図３の眼球分析装置は、図１の眼球分析装置と同じである。 [Embodiment 3]
FIG. 3 shows still another example of the configuration of the eyeball analyzer of the present invention. As shown in the drawing, in this eyeball analyzer, a polarizing plate 61 is disposed between the lens 11 and the beam splitter 12 in the light irradiation means 10. Further, in the unit 100, 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.
　図３の眼球分析装置は、例えば、以下のようにして使用することができる。まず、図１と同様、光源１０Ａから連続光を照射させる。光源１０Ａから照射された連続光は、レンズ１１によって収束された後、偏光板６１によって直線偏光にされる。偏光された前記連続光は、ビームスプリッタ１２、レンズ１３によって図１と同様に処理されて眼球１に照射され、さらに、その少なくとも一部が、眼球１からの出射光となってレンズ１３およびビームスプリッタ１２を通過する。 3 can be used as follows, for example. First, as in FIG. 1, 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.
　ビームスプリッタ１２を透過した前記出射光は、ユニット１００により、以下のように処理される。すなわち、まず、前記出射光は、光分離手段２０の像面２１およびレンズ２２によって、図１と同様に処理され、眼球１の空間の位置に応じて分離される。つぎに、レンズ２２を透過した前記出射光は、１／２波長板２３に入射する。１／２波長板２３は、回転させることが可能であり、これにより、前記出射光の直線偏光の方位を変えることができる。１／２波長板２３を透過した前記出射光は、偏光板２４により、特定の方向の直線偏光が選択的に出射され、その後、波長可変フィルター３１により、波長ごとに分離され、特定波長の単色光が取り出される。取り出された単色光は、レンズ４１、撮像手段２０および任意にスペクトル解析手段（図示せず）により、図１と同様に処理される。このとき、前記スペクトル解析手段によって異なる方向の直線偏光の分光スペクトルを比較することにより、眼球１の少なくとも一部における、左右の円偏光に対する屈折率の違い（旋光性）が検出されてもよい。 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.
　なお、本発明において、偏光板の配置および使用方法は、図３の例に限定されない。例えば、直線偏光板に代えて、円偏光板を用い、眼球１に入射する光または眼球1から出射（射出）される光を円偏光しても良い。円偏光板を用いた場合は、例えば１／２波長板２３を回転可能な１／４波長板に置き換えるか、または、１／２波長板２３の光入射側または光出射側に隣接して、回転可能な１／４波長板を用いても良い。円偏光板（円偏光手段）６１は、例えば、透過させる円偏光の回転方向の左右を切り替え可能であっても良い。また、前記１／４波長板により、円偏光を直線偏光に変換することができる。また、１／２波長板２３により、直線偏光の方位または円偏光の回転方向を変えることができる。このようにすれば、例えば、眼球１の少なくとも一部における、左右の円偏光に対する吸光度の違いを検出することができる。これにより、例えば、眼球１中の光学異性体の検出を行うことができる。前記光学異性体としては、例えば、アミノ酸又はアミノ酸残基のL体とD体が挙げられる。 In the present invention, the arrangement and usage of the polarizing plate are not limited to the example of FIG. For example, 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. When the circularly polarizing plate is used, 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. For example, 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. Moreover, 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. In this way, for example, 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. Thereby, for example, 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.
［本発明の用途］
　本発明の眼球分析装置および眼球分析方法は、例えば、以下の用途に用いることができる。ただし、これらは例示であって、本発明をなんら限定しない。 [Use of the present invention]
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.
　本発明によれば、例えば、眼球内において、前記眼球への光の入射方向に対し垂直な面を、前記眼球の空間の位置に応じて分析することができる。分析対象とする前記面は、特に限定されないが、例えば、眼底であっても良いし、網膜、角膜、または水晶体の少なくとも一部であっても良い。 According to the present invention, for example, 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.
　また、本発明によれば、前記眼球からの出射光を波長ごとに分光することにより、例えば、前記面方向の分析において、さらに波長を変化させた分析（三次元分光分析）を行うことができる。図４に、本発明における三次元分光分析の概念を模式的に示す。図４は、前記平面方向（Ｘ方向およびＹ方向とする）に加え、さらに、波長の変化（Ｚ方向とする）に応じた分析を行うことを示している。異なる波長帯で三次元分光分析を行うことによって、例えば、眼底断層写真の撮像により、赤外線波長の違いによる深度の違いの分析を行うことができる。また、例えば、可視光または赤外線の特定の波長の吸収を利用して、白内障検査に用いることができる。また、例えば、眼内血管、視神経等の撮像により、可視光の特定の波長での分光分析を行うことができる。なお、本発明において「眼底断層」は、眼底および眼底よりも下層の間の空間の断層を含む。 Further, according to the present invention, by analyzing the light emitted from the eyeball for each wavelength, for example, in the analysis in the plane direction, an analysis (three-dimensional spectroscopic analysis) in which the wavelength is further changed can be performed. . 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. By performing three-dimensional spectroscopic analysis in different wavelength bands, it is possible to analyze differences in depth due to differences in infrared wavelengths, for example, by capturing fundus tomographic photographs. In addition, for example, it can be used for a cataract examination using absorption of a specific wavelength of visible light or infrared light. For example, spectroscopic analysis at a specific wavelength of visible light can be performed by imaging an intraocular blood vessel, an optic nerve or the like. In the present invention, the “fundus tomography” includes a tomography of the space between the fundus and the lower layer than the fundus.
　また、本発明によれば、例えば、前記眼球への光の入射方向に対し垂直な面方向に加え、前記光の入射方向に平行な方向（前記眼球の奥行き方向）も含めて三次元的に分析することも可能である。また、これに加え、さらに波長を変化させた分析（四次元分光分析）を行うことができる。また、例えば、前記波長を変化させた四次元分光分析に加え、さらに、測定時刻を変化させた（測定方向に時間を加えた）五次元分光分析も可能である。 Further, according to the present invention, for example, in addition to a plane direction perpendicular to the incident direction of light to the eyeball, the direction parallel to the incident direction of light (the depth direction of the eyeball) 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.
　また、本発明によれば、例えば、前記眼球内の空間の特定位置において、前記特定位置からの出射光の波長と、前記出射光の偏光方位角（Δθ）との関係を二次元的にプロットすることで、前記特定位置における眼球の状態を分析できる。前記眼球の状態としては、例えば、疾患の進行度合い等が挙げられる。より具体的には、例えば、前記特定位置における波長と偏光方位角（Δθ）との関係から、前記特定位置におけるＬ－アルギン酸とＤ－アルギン酸との割合を算出し、これにより、前記特定位置における白内障の進行度合いを判断できる。また、同様にして前記眼球内の様々な位置の波長と偏光方位角（Δθ）との関係をプロットすることで、前記様々な位置の疾患の進行度合いを判断できる。 Further, according to the present invention, for example, at a specific position in the space inside the eyeball, the relationship between the wavelength of the emitted light from the specific position and the polarization azimuth angle (Δθ) of the emitted light is plotted two-dimensionally. By doing so, the state of the eyeball at the specific position can be analyzed. Examples of 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 (Δθ). The degree of progression of cataract can be judged. Similarly, by plotting the relationship between the wavelength at various positions in the eyeball and the polarization azimuth angle (Δθ), the degree of progression of the disease at the various positions can be determined.
　また、本発明の用途は、前記の説明に限定されず、眼球分析における任意の用途に広く使用可能である。例えば、本発明は、タンパク質（クリスタリンなど）の変性、眼球に分泌される物質などの分析に用いることができる。具体的には、例えば、眼球中のアミロイドタンパク質の分析により、アルツハイマー病の早期発見等に用いることができる。また、例えば、水晶体構成タンパク質（クリスタリン）中のトリプトファンが、酸化されたキヌレニンもしくは３-ヒドロキシキヌレニンを分析することで、または、タンパク質中のリジン残基と体内の糖が結合してできたAGE（advanced　glycated　end　products)を分析することで、前述した白内障の早期発見も可能である。また、例えば、本発明は、透過力が高い長波長の光を用いることにより、眼底の深部、または、眼底および眼底よりも下層の間の空間まで分析可能であり、これにより、視神経の状態、毛細血管の状態、網膜の状態などを分析することができる。また、本発明によれば、例えば、非侵襲的に、かつ簡便に眼球の分析を行うことができる。 The application of the present invention is not limited to the above description, and can be widely used for any application in eyeball analysis. For example, 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. In addition, for example, tryptophan in the lens-constituting protein (crystallin) 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. Further, for example, 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. Further, according to the present invention, for example, the eyeball can be analyzed non-invasively and simply.
　また、本発明では、例えば、前述のとおり、眼球に照射する光を、複数の波長の光を含む混合光（例えば、白色光、ＳＣ光等の連続光、または複数の単色光の混合光）とすることができる。現在広く用いられている波長掃引型OCT(SS-OCT：Swept　Source　Optical　Coherence　Tomography)では、複数の波長の光を時間的に分けて入射するため、測定（分析）時間が長くなり、患者への負担も大となる。これに対し、本発明においては、例えば、前記複数の波長の光を含む混合光を一度だけ眼球に照射するのみで眼球の分析が可能である。これにより、SS-OCTと比較して分析時間を大幅に短縮可能であり、患者への負担を軽減できる。ただし、この説明は例示であり、本発明をなんら限定しない。 In the present invention, for example, as described above, 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. In the wavelength sweep type OCT (SS-OCT: Swept Source Optical Coherence Tomography), which is widely used at present, 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. On the other hand, in the present invention, for example, 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. However, this description is merely an example and does not limit the present invention.
　以上、実施形態１～３により、本発明の眼球分析装置および眼球分析方法の例について説明し、さらに、本発明の用途の例について説明した。ただし、本発明は、これらに限定されず、任意の変更が可能である。例えば、分光法としては、CARS等のラマン分光法を用いることができるが、これに限定されず、一般的に用いられる任意の分光法を使用可能である。 As described above, 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.
　以上、説明したとおり、本発明によれば、眼球の状態の微細な変化も検出可能で、疾患の早期発見等に有用な眼球分析装置および眼球分析方法を提供することができる。これにより、本発明は、眼球の状態に関連した各種疾患の早期発見等に多大な貢献が可能である。 As described above, according to 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. Thus, the present invention can greatly contribute to early detection of various diseases related to the state of the eyeball.
１０　光照射手段
１０Ａ　光源
１１、１３、２２、４１、　レンズ
１２　ビームスプリッタ
２０　撮像手段（光分離手段）
２１　像面
２３　１／２波長板
２４　偏光板
６１　偏光板または円偏光板（円偏光手段）
３１　波長可変フィルター（分光手段）
３２　狭帯域フィルター
１００　光分離および分光ユニット DESCRIPTION OF SYMBOLS 10 Light irradiation means 10A Light source 11, 13, 22, 41, Lens 12 Beam splitter 20 Imaging means (light separation means)
21 Image plane 23 Half-wave plate 24 Polarizing plate 61 Polarizing plate or circularly polarizing plate (circularly polarizing means)
31 Wavelength variable filter (spectral means)
32 Narrow band filter 100 Light separation and spectroscopy unit

Claims (7)

  1. 光照射手段、光分離手段、分光手段を含み、
    前記光分離手段が、撮像手段を含み、
    前記分光手段が、波長可変フィルターを含み、
    前記光照射手段により、光が眼球に照射され、
    前記波長可変フィルターにより、前記光を照射された前記眼球から出射する出射光が、分光され、
    前記撮像手段により、前記分光された出射光が撮像され、撮像して得られた画像上の画素によって、前記分光された出射光が、前記眼球の空間の位置に応じて二次元的に分離される、
    眼球分析装置。     Including light irradiation means, light separation means, spectroscopic means,
    The light separating means includes imaging means;
    The spectroscopic means includes a wavelength tunable filter,
    The light is irradiated to the eyeball by the light irradiation means,
    Outgoing light emitted from the eyeball irradiated with the light is split by the wavelength tunable filter,
    The spectrally emitted light is imaged by the imaging means, and the spectrally emitted light is two-dimensionally separated according to the position of the eyeball space by pixels on the image obtained by imaging. The
    Eye analysis device.
  2. 前記分光手段が、さらに、狭帯域フィルターを含み、
    前記分光された出射光が前記狭帯域フィルターを通過する、
    請求項１記載の眼球分析装置。     The spectroscopic means further includes a narrow band filter,
    The split outgoing light passes through the narrowband filter;
    The eyeball analyzer according to claim 1.
  3. さらに、円偏光手段を含み、
    前記円偏光手段により、前記眼球に入射する光が、円偏光される、
    請求項１または２記載の眼球分析装置。     And further includes a circular polarization means,
    The circularly polarized light is incident on the eyeball by the circularly polarizing means,
    The eyeball analyzer according to claim 1 or 2.
  4. さらに、円偏光分析手段を含み、
    前記円偏光分析手段により、前記眼球の少なくとも一部における、左右の円偏光に対する吸光度の違いが検出される、請求項３記載の眼球分析装置。     In addition, circular polarization analysis means,
    The eyeball analyzer according to claim 3, wherein a difference in absorbance with respect to left and right circularly polarized light in at least a part of the eyeball is detected by the circularly polarized light analyzing means.
  5. さらに、直線偏光手段を含み、
    前記直線偏光手段により、前記連続光を照射された前記眼球から出射する出射光が、直線偏光される、
    請求項１から４のいずれか一項に記載の眼球分析装置。     And further includes linear polarization means,
    Outgoing light emitted from the eyeball irradiated with the continuous light is linearly polarized by the linearly polarizing means.
    The eyeball analyzer according to any one of claims 1 to 4.
  6. さらに、直線偏光分析手段を含み、
    前記直線偏光分析手段により前記直線偏光が分析されることで、前記眼球の少なくとも一部における、左右の円偏光に対する屈折率の違いが検出される、
    請求項５記載の眼球分析装置。     And further includes linear polarization analysis means,
    By analyzing the linearly polarized light by the linearly polarized light analyzing means, a difference in refractive index with respect to left and right circularly polarized light in at least a part of the eyeball is detected.
    The eyeball analyzer according to claim 5.
  7. 眼球に光を照射する照射工程と、
    前記照射された眼球から出射する出射光を、分光する分光工程と、
    前記照射された眼球から出射する出射光を、前記眼球の空間の位置に応じて分離する光分離工程と、
    を含み、
    前記分光工程において、波長可変フィルターにより、前記出射光を分光し、
    前記光分離工程において、前記分光された出射光を撮像し、撮像して得られた画像上の画素によって前記分光された出射光を二次元的に分離する、
    眼球分析方法。     An irradiation step of irradiating the eyeball with light;
    A spectroscopic step of splitting the outgoing light emitted from the irradiated eyeball;
    A light separation step of separating the emitted light emitted from the irradiated eyeball according to the position of the space of the eyeball;
    Including
    In the spectroscopic step, the emitted light is dispersed by a wavelength variable filter,
    In the light separation step, the dispersed outgoing light is imaged, and the dispersed outgoing light is two-dimensionally separated by pixels on an image obtained by imaging.
    Eye analysis method.
PCT/JP2017/025508 2016-07-19 2017-07-13 Eye analysis device and eye analysis method WO2018016409A1 (en)

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