JP6161693B2 - Fluorescence measuring apparatus and fluorescence measuring method - Google Patents

Description

  The present invention relates to a fluorescence measuring apparatus and a fluorescence measuring method for performing measurement by irradiating an eyeball of a subject with excitation light and receiving fluorescence from the eyeball.

  In recent years, research on AGEs (advanced glycation end products) produced by glycation of proteins in vivo has been actively conducted. Among AGEs, Pentosidine, Crossline, Pyrropyridine, Vesperlysine A, B, C, Argpyrimidine, GApyridine (GA-Pyridine), K2P (Lysine dihydropyridinium) crosslink), and those having fluorescence such as Lys-Hydroxy-triosidine, and those that form a crosslink between proteins. It is considered that the collagen fibers constituting the dermis and blood vessel walls lose their flexibility due to the crosslinking action of AGEs, resulting in skin wrinkles and blood vessel deterioration. In addition, AGEs are thought to cause inflammation and oxidative stress by binding to receptors (RAGE) in cells in the body, causing various tissue damage, and causing diabetes complications and age-related diseases. ing.

  According to the 2011 report of the International Diabetes Federation, there are about 366 million people with diabetes worldwide, and the annual medical costs are estimated at about $ 465 billion. Due to factors such as aging in developed countries such as Japan and changing lifestyles in emerging countries, the number of patients with diabetes and medical costs are increasing.

  Diabetes complications are vascular disorders, and are likely to occur at sites where thin blood vessels such as the retina and kidneys accumulate. This is also considered to be caused by accumulation of AGEs in the tissue of the blood vessel wall. In addition, not only for diabetics but also for healthy individuals, AGEs accumulate with age, so osteoporosis, dementia, arteriosclerosis, cataract, glaucoma, age-related macular degeneration, corneal degeneration, muscle loss AGEs are suspected to be involved in many age-related diseases such as dementia.

  Therefore, if the degree of accumulation of AGEs in the body is grasped, it can be expected to be useful for grasping the status of diabetic complications and age-related diseases and future onset risk for unaffected individuals. In addition, it can be expected that grasping the accumulation of AGEs in the body will be useful for the testing of anti-aging effect and prevention of AGEs by pharmaceuticals and foods.

  As a method for measuring AGEs in the body, for example, there is a method in which a sample of blood or tissue is collected from a subject and analyzed using a liquid chromatograph or a mass spectrometer, or analyzed by enzyme immunoassay. . However, in such a method, there is a problem that collection of a sample is invasive, and the subject is painful, and that a lot of time and cost are required for the examination.

  Therefore, Patent Document 1 below proposes a method of irradiating a part of tissue made of skin with excitation light and detecting fluorescence emitted from the tissue. Patent Document 2 below proposes a method for diagnosing diseases such as diabetes by irradiating light to an eye lens, separating backscattered luminescence into fluorescence and Rayleigh components, and detecting the respective intensities. ing.

Japanese Patent No. 5053699 Japanese National Patent Publication No. 7-500030

  Although the method of irradiating the skin with the excitation light as described in Patent Document 1 is non-invasive, there is a problem that the measurement value is not stable because the subcutaneous dermis tissue is the measurement target. That is, the amount of body hair that exists between the time when the excitation light is delivered to the dermis and the fluorescence emitted from the dermis is received, and individual differences such as the color and thickness of the epidermis affect the measured value. There's a problem.

  On the other hand, in the method of irradiating light to an eye lens (crystal lens) as in Patent Document 2, light enters the subject's black eye, so the amount of light irradiation for ensuring biological safety However, there is a problem that the measurement sensitivity is lowered. In front of the crystalline lens, although it is generally optically transparent, there is a cornea and aqueous humor layer, and it is inevitable that interference effects such as scattering and absorption occur. There are also subjects who feel uneasy even if the irradiation dose meets safety standards (ICNIRP guidelines, IEC 62471, JIS C7550, etc.). Furthermore, cataracts in which the lens is cloudy is an eye disease that occurs in the majority of the elderly, but the lens itself cannot be measured after cataract surgery because the clouded lens is removed in cataract surgery.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide a fluorescence measuring apparatus and a fluorescence measuring method capable of improving safety and obtaining a stable measurement value. .

  The inventors of the present application have focused on the eyeball, which is a part of the human body that has extremely small racial and individual differences, and as a result of repeated research, the sclera of the eyeball has been measured. The sclera of the eyeball is mainly formed of collagen fibers, like the blood vessel wall and dermis, and it is considered that AGEs progress in a manner similar to those sites.

The fluorescence measurement device according to the present invention includes an excitation light irradiation unit that emits excitation light that can emit fluorescence from the sclera toward the sclera of a subject's eyeball, and a sclera irradiated with the excitation light. A fluorescence light receiving unit that receives fluorescence from the light receiving unit, and a calculation unit that performs calculation based on the received light intensity in the fluorescence light receiving unit.

  According to such a configuration, it is possible to improve safety by irradiating excitation light toward the sclera of the eyeball, receiving fluorescence from the sclera and performing calculations, and performing stable measurement. A value can be obtained. The sclera is a strong tissue that forms the eyeball, has a function of scattering light, and there is a choroid that blocks light below it, so that light can enter the eyeball from the sclera, which is important for visual function. Absent. That is, since the excitation light can be prevented from entering the inside of the eyeball by irradiating the sclera with the excitation light instead of the lens of the eyeball, safety can be improved. In addition, among the eyeballs with extremely small race differences and individual differences, the sclera, in particular, has only a thin and transparent conjunctiva on it, and there are very few obstacles that prevent the passage of excitation light and fluorescence, so stable measurement is possible. A value can be obtained.

  The fluorescence measuring apparatus may further include a line-of-sight guiding unit for guiding the line of sight of the subject in a direction different from the incident direction of the excitation light.

  According to such a configuration, it is possible to securely irradiate the excitation light toward the sclera of the eyeball by guiding the subject's line of sight in a direction different from the incident direction of the excitation light. Can be further improved. Further, if the subject's line of sight is continuously guided during measurement, it is possible to prevent the eyeball from moving due to a change in line of sight during the measurement, and thus a stable measurement value can be obtained. In addition, since different eyes can direct the line of sight in the same direction, the relative irradiation position of the excitation light to the sclera of the eyeball can be kept constant, and more stable measurement values can be obtained. Can do.

  It is preferable that the line-of-sight guide unit guides the line of sight upward from the front with respect to the eyeball. When the line of sight is guided below the front with respect to the eyeball, the subject tends to close the eyelid. Therefore, by guiding the line of sight upward from the front with respect to the eyeball, it is possible to prevent the subject from easily closing the eyelid and to irradiate excitation light toward the sclera of the eyeball satisfactorily. .

  The excitation light irradiation unit may irradiate excitation light toward the sclera of one eyeball of the subject. In this case, the line-of-sight guiding unit may guide the line of sight of the one eyeball of the subject, or may guide the line of sight of the other eyeball of the subject. Even when the line of sight of the other eyeball of the subject is guided by the line-of-sight guide unit, the line of sight of the one eyeball is also guided in the same direction as the natural eyeball. The line of sight of the one eyeball) can be guided well.

  The fluorescence measurement apparatus may further include an irradiation light guide unit that guides excitation light irradiated from the excitation light irradiation unit to a standard sample having known fluorescence characteristics. In this case, it is preferable that the calculation unit performs a calculation based on the fluorescence from the sclera received by the fluorescence light receiving unit and the received light intensity of the fluorescence from the standard sample.

  According to such a configuration, by using the fluorescence received light intensity from the standard sample as the reference value, the fluorescence received light intensity from the sclera can be obtained as a relative measurement value. The received light intensity in the fluorescent light receiving unit may not be kept constant due to variations in characteristics of each component or changes over time. Even in such a case, a more stable measurement value can be obtained by converting a relative measurement value using a standard sample having known fluorescence characteristics as a reference.

  The irradiation light guide unit includes a first irradiation light guide unit that guides excitation light irradiated from the excitation light irradiation unit to the sclera, and a second unit that guides excitation light irradiated from the excitation light irradiation unit to the standard sample. You may branch to the irradiation light guide part.

  According to such a structure, the excitation light irradiated from the same excitation light irradiation part is simultaneously guide | induced to a sclera and a standard sample. Therefore, when the excitation light irradiated from the excitation light irradiation unit is unstable, both the fluorescence received light intensity from the standard sample and the fluorescence received light intensity from the sclera vary. Therefore, a more stable measurement value can be obtained by converting the light reception intensity of the fluorescence from the sclera into a relative measurement value using the light reception intensity of the fluorescence from the standard sample as a reference value.

  The fluorescence measurement apparatus may further include a scattered light receiving unit that receives excitation light scattered in the eyeball. In this case, it is preferable that the calculation unit performs a calculation based on the light reception intensity in the fluorescence light reception unit and the light reception intensity in the scattered light reception unit.

  According to such a configuration, the received light intensity of the fluorescence from the sclera can be corrected using the received light intensity of the scattered light in the scattered light receiving unit. In addition to fluctuations in the intensity of the excitation light emitted by the light source, if the illuminance of the excitation light in the eyeball or the light collection efficiency from the eyeball changes due to variations in the position of the irradiation mechanism and light reception mechanism on the eyeball, the fluorescence light receiving unit In some cases, the received light intensity of the fluorescence varies. In such a case, the received light intensity of the scattered light in the scattered light receiving unit also varies in the same manner. Therefore, by correcting the received light intensity of the fluorescence from the sclera using the received light intensity of the scattered light. More stable measurement values can be obtained.

  It is preferable that the excitation light irradiation unit irradiates the excitation light at an angle of 30 to 60 ° with respect to the normal line at the excitation light irradiation center on the eye sphere.

  According to such a configuration, for example, even when there is another member such as an imaging unit in the normal direction at the irradiation center of the excitation light on the eyeball surface, the side is relatively close to the eyeball. Excitation light can be irradiated from the position. Thereby, the illumination intensity of the excitation light in the eyeball can be increased and the sensitivity of measurement can be improved.

  It is preferable that the excitation light from the excitation light irradiation unit is applied to the eyeball from the outer corner of the eye. In addition, the fluorescence from the sclera is preferably measured on the lower side of the front than the front. This can prevent the eyelashes from interfering with the passage of excitation light and fluorescence, thereby improving measurement accuracy. In this case, if the configuration is such that the fluorescence from the sclera is measured on the outer corner of the eyeball, the excitation light that is regularly reflected by tears on the eyeball is prevented from being received by the scattered light receiver. Therefore, the measurement accuracy can be further improved.

  The fluorescence measurement apparatus may further include an imaging unit that images the eyeball of the subject and a display unit that displays an image captured by the imaging unit.

  According to such a configuration, since the image captured by the imaging unit is displayed on the display unit, the operator confirms the state of the eyeball of the subject based on the image displayed on the display unit, and appropriately Measurements can be made. The state of the eyeball of the subject includes, for example, the direction of the line of sight of the subject, the irradiation position and irradiation state of the excitation light on the eyeball, and the degree of eyelid opening.

  The fluorescence light receiving unit may be configured by an imaging unit that images the eyeball of the subject. In this case, it is preferable that the calculation unit performs a calculation based on the received light intensity obtained from the image captured by the imaging unit.

  According to such a configuration, since the fluorescence light receiving unit that receives fluorescence from the sclera is configured by the imaging unit that images the eyeball of the subject, the number of components can be reduced and the manufacturing cost can be reduced. Can do. In this case, it is preferable that an optical filter that transmits only the fluorescence wavelength is detachably provided between the sclera of the eyeball and the imaging unit. In addition, if the standard sample is provided around the eyeball in the imaging region of the imaging unit, fluorescence from both the sclera and the standard sample can be imaged simultaneously, and thus an efficient and stable measurement value. Can be obtained.

  The fluorescence measuring device includes a light receiving light guide unit that guides light from an eyeball to the fluorescence light receiving unit, a branch light guide unit branched from the light receiving light guide unit, and the branch light guide unit through the light receiving light guide unit. And an adjustment irradiator that irradiates the eyeball with adjustment light.

  According to such a configuration, it is possible to irradiate the eyeball with light for adjustment via the light receiving and guiding section that guides light from the eyeball to the fluorescence light receiving section. Therefore, by confirming the irradiation position of the adjustment light on the eyeball, the position on the eyeball where the fluorescence is received by the fluorescence light receiving unit can be recognized. Accordingly, the position of the optical system can be adjusted while confirming the irradiation position of the adjustment light, and the fluorescence can be received by the fluorescent light receiving unit at an appropriate position, so that the measurement accuracy can be improved.

  The fluorescence measuring device is provided separately from a light receiving light guide unit that guides light from an eyeball to the fluorescence light receiving unit, an adjustment irradiation unit that irradiates adjustment light to the eyeball, and the light receiving light guide unit, You may further provide the adjustment light guide part which guides the light for adjustment from the irradiation part for adjustment to an eyeball.

  According to such a configuration, the adjustment light can be irradiated to the eyeball from the adjustment irradiation unit via the adjustment light guide provided separately from the light receiving light guide. In the case of the configuration provided with the branch light guide unit, a part of the light from the eyeball guided to the fluorescence light receiving unit side at the time of measurement is also guided to the branch light guide unit, so that the light receiving intensity in the fluorescence light receiving unit decreases. However, when the adjustment light guide unit is provided separately as in the present invention, it is possible to prevent a decrease in the light receiving intensity in the fluorescence light receiving unit and improve the measurement sensitivity.

  The fluorescence measurement apparatus may further include a housing that houses the excitation light irradiation unit and the fluorescence light receiving unit. In this case, the housing may be provided with a contact surface that contacts the mounting table when the housing is mounted. Thereby, it is possible to provide a desktop fluorescence measuring apparatus that is used by being placed on a mounting table.

  On the other hand, the housing may be provided with a grip portion for the operator to grip. In this case, it is possible to provide a handy-type fluorescence measuring apparatus that is used by the operator holding the grip portion. The grip part may be provided with an operation part that can be operated by a hand that the operator grips the grip part.

The fluorescence measurement method according to the present invention includes an excitation light irradiation step of irradiating excitation light that can emit fluorescence from the sclera toward the sclera of the subject's eyeball from the excitation light irradiation unit, It includes a fluorescence light receiving step in which the fluorescence from the irradiated sclera is received by the fluorescence light receiving unit, and a calculation step in which the calculation unit performs a calculation based on the received light intensity in the fluorescence light receiving unit.

  According to the present invention, since the excitation light can be prevented from entering the inside of the eyeball by irradiating the sclera of the eyeball with the excitation light, safety can be improved. In addition, according to the present invention, the excitation light is irradiated toward the sclera of the eyeball with very little obstacles that block the passage of excitation light and fluorescence, and the calculation is performed by receiving the fluorescence from the sclera and performing the calculation. Measurements can be obtained.

It is the schematic which showed the structural example of the fluorescence measuring apparatus which concerns on one Embodiment of this invention. It is the schematic for demonstrating the other structure with which the fluorescence measuring apparatus of FIG. 1 was equipped. It is the schematic which showed the 1st modification of the structure of the fluorescence measuring apparatus. It is the schematic which showed the 2nd modification of the structure of the fluorescence measuring apparatus. It is the schematic which showed the 3rd modification of the structure of the fluorescence measuring apparatus. It is the schematic plan view which showed an example of the positional relationship of an irradiation light guide part and an imaging part. FIG. 7 is a diagram viewed from an arrow A in FIG. 6, illustrating an example of a positional relationship between an irradiation light guide unit and a light reception light guide unit. It is the schematic which showed the 4th modification of the structure of the fluorescence measuring apparatus. It is the schematic which showed an example of the image imaged by the imaging part of FIG. It is the schematic which showed the 5th modification of the structure of the fluorescence measuring apparatus. It is a figure for demonstrating the aspect at the time of adjusting the position of an optical system in the fluorescence measuring device of FIG. 10, and has shown an example of the image in the imaging region imaged with an imaging part during adjustment. It is the schematic which showed the 6th modification of the structure of the fluorescence measuring apparatus. It is a figure for demonstrating the aspect at the time of adjusting the position of an optical system in the fluorescence measuring device of FIG. 12, and shows an example of the image in the imaging area imaged with an imaging part during adjustment. It is the schematic which showed the structural example of the fluorescence measuring apparatus which concerns on another embodiment.

  FIG. 1 is a schematic diagram illustrating a configuration example of a fluorescence measuring apparatus according to an embodiment of the present invention. This fluorescence measuring apparatus emits fluorescence from the sclera 11 by irradiating the sclera 11 of the subject's eyeball 1 with excitation light, and receives the fluorescence from the sclera 11 for measurement. Is what you do. The fluorescence measuring apparatus according to this embodiment includes an irradiation mechanism 2 for irradiating excitation light toward the sclera 11 of the eyeball 1 of a subject, and a light receiving mechanism 3 for receiving light from the sclera 11. Is provided.

  The irradiation mechanism 2 includes a light source 21, a lens 22, an optical filter 23, a lens 24, and the like. The light source 21 is an excitation light irradiation unit that irradiates excitation light toward the sclera 11 of the eyeball 1 of the subject, and is configured by, for example, a light emitting diode. As the excitation light emitted from the light source 21, for example, ultraviolet rays having a wavelength of about 330 to 380 nm can be used to suitably excite AGEs. However, the light source 21 is not limited to the light emitting diode, and may be another configuration such as a mercury lamp or a xenon lamp.

  The excitation light emitted from the light source 21 is converted into parallel light by the lens 22, then light having an unnecessary wavelength is removed by the optical filter 23, and only the light having the excitation wavelength is condensed by the lens 24 to strengthen the eyeball 1. The film 11 is irradiated. The optical system such as the lens 22, the optical filter 23, and the lens 24 constitutes an irradiation light guide 102 that guides excitation light emitted from the light source 21.

  The light receiving mechanism 3 includes a lens 31, an optical filter 32, a lens 33, a photodetector 34, and the like. The light emitted from the irradiation position of the excitation light in the sclera 11 of the eyeball 1 is collimated by the lens 31 and then enters the optical filter 32. The light from the irradiation position includes not only fluorescence but also scattered light having the same wavelength as the excitation light, but only the fluorescence wavelength can be transmitted by the optical filter 32. The fluorescence transmitted through the optical filter 32 is collected by the lens 33 and received by the photodetector 34. The optical system such as the lens 31, the optical filter 32, and the lens 33 constitutes a light receiving / guiding unit 103 that guides light from the eyeball 1 to the photodetector 34.

  The photodetector 34 is a fluorescence light receiving unit that receives fluorescence from the sclera 11 irradiated with excitation light, and is configured by, for example, a photodiode or a photomultiplier tube. As the photodetector 34, for example, the fluorescence can be suitably received by using the photodetector 34 having sensitivity to a wavelength of about 350 to 600 nm which is a fluorescence wavelength region of AGEs. However, the configuration is not limited to the configuration in which the fluorescence from the sclera 11 is received by the single-channel photodetector 34, but the fluorescence is dispersed by a spectroscope such as a diffraction grating and received by a multi-channel photodetector. It is also possible to obtain a spectral spectrum.

  A detection signal from the photodetector 34 is input to the calculation unit 4. The calculation unit 4 is configured by a CPU (Central Processing Unit), for example, and performs calculation based on the received light intensity in the photodetector 34. Thereby, the measured value according to the accumulation amount of AGEs can be obtained.

  In the present embodiment, the safety can be improved by performing excitation by irradiating the sclera 11 of the eyeball 1 with excitation light, receiving the fluorescence from the sclera 11, and performing stable measurement. A value can be obtained. The sclera 11 is a strong tissue that forms the eyeball 1, has a function of scattering light, and there is a choroid that blocks light below it, so that light is transmitted from the sclera 11 into the eyeball 1 that is important for visual function. Will not enter. That is, by irradiating the sclera 11 with excitation light instead of the lens of the eyeball 1, it is possible to prevent the excitation light from entering the inside of the eyeball 1, so that safety can be improved. Further, among the eyeballs 1 with extremely small racial differences and individual differences, the sclera 11 is particularly stable because it has only a thin and transparent conjunctiva on it, and there are very few obstacles that prevent the passage of excitation light and fluorescence. Measured values can be obtained.

  According to experiments conducted by the inventors of the present application, when fluorescence is measured by irradiating the sclera 11 of the eyeball 1 of the subject with the excitation light, the skin of the subject is irradiated with the same excitation light illuminance. The received light intensity was about 4 times greater than when fluorescence was measured. This experiment was performed by using ultraviolet rays having a wavelength of 365 nm as excitation light and integrating the fluorescence amount in the wavelength range of 440 to 480 nm for 1 second. The subject was a man in his 40s and a healthy person. From this experimental result, it can be seen that the measurement superiority can be obtained by using the sclera 11 of the eyeball 1 having no obstacles such as epidermis and body hair as a measurement object.

  The characteristics of components such as the light source 21, the optical filters 23 and 32, and the photodetector 34 vary from device to device. Even with the same device, the intensity of the light source 21 and the sensitivity of the photodetector 34 change over time. Therefore, in the present embodiment, the measurement can be performed using the standard sample 5 having a known fluorescence characteristic so that the measurement results at different apparatuses or different measurement dates can be compared.

  Specifically, the excitation light from the light source 21 is applied to the standard sample 5 by setting the standard sample 5 to the position where the eyeball 1 of the subject is measured, that is, the irradiation position of the excitation light from the light source 21. Can be irradiated. At this time, the irradiation light guide unit 102 including the lens 22, the optical filter 23, the lens 24, and the like guides the excitation light irradiated from the light source 21 to the standard sample 5. The standard sample 5 may be set manually by an operator at the start of work or may be set automatically.

  In this case, the calculation unit 4 can perform calculation based on the fluorescence from the sclera 11 received by the photodetector 34 and the received light intensity of the fluorescence from the standard sample 5. For example, a configuration may be used in which the light reception intensity of the fluorescence from the sclera 11 is converted into a relative value using the light reception intensity of the fluorescence from the standard sample 5 as a reference.

  As described above, in this embodiment, by using the fluorescence received light intensity from the standard sample 5 as a reference value, the fluorescence received light intensity from the sclera 11 can be obtained as a relative measurement value. As described above, the received light intensity in the photodetector 34 may not be kept constant due to variations in characteristics of components or changes over time. Even in such a case, a more stable measurement value can be obtained by converting the standard sample 5 having a known fluorescence characteristic into a relative measurement value.

  FIG. 2 is a schematic diagram for explaining another configuration provided in the fluorescence measuring apparatus of FIG. The fluorescence measuring apparatus includes, for example, a housing 6. In the housing 6, in addition to the irradiation mechanism 2, the light receiving mechanism 3, and the calculation unit 4, a line-of-sight guidance unit 7 and an imaging unit 8 are provided. Contained. Since the housing 6 can prevent light from entering from the outside, more stable measurement values can be obtained.

  The housing 6 is provided with an eyepiece 61, and the subject can position the eye by bringing the eyepiece 61 into contact with the periphery of the eye. Only one eyepiece 61 may be provided in association with one eye to be measured, or two eyepieces 61 may be provided in association with both eyes of the subject. This fluorescence measurement device is a desktop fluorescence measurement device that is used in a state where the housing 6 is placed on the placement table T. The lower surface of the housing 6 constitutes a contact surface 62 that contacts the mounting table T when the housing 6 is mounted.

  The line-of-sight guiding unit 7 is for guiding the line of sight of the subject in a direction different from the incident direction of the excitation light, and includes, for example, a light source 71 and a lens 72. The light source 71 emits visible light, and the visible light passes through the lens 72 and enters the eyeball 1 of the subject. However, the line-of-sight guiding unit 7 may not include the lens 72.

  The line-of-sight guiding unit 7 is not limited to the configuration that guides the subject's line of sight with light, and can guide the subject's line of sight using various means that the subject can visually recognize. it can. Furthermore, the configuration may be such that the line of sight of the subject is guided by outputting sound from the speaker, or the line of sight guidance unit 7 is omitted and the line of sight of the subject is guided by the operator's instruction. It may be a simple configuration.

  In this way, by guiding the subject's line of sight in a direction different from the incident direction of the excitation light, the excitation light can be reliably irradiated toward the sclera 11 of the eyeball 1, so that safety is further improved. Can be improved. Further, if the subject's line of sight is continuously guided during the measurement, it is possible to prevent the eye 1 from moving due to a change in the line of sight during the measurement, so that a stable measurement value can be obtained. Furthermore, since different eyes can direct the line of sight in the same direction, the relative irradiation position of the excitation light to the sclera 11 of the eyeball 1 can be kept constant, and a more stable measurement value can be obtained. Can be obtained.

  In the present embodiment, the line-of-sight guiding unit 7 guides the line of sight to the eyeball 1 above the front side. When the eye gaze is guided downward from the front with respect to the eyeball 1, the subject tends to close the eyelid, but by guiding the eye gaze upward from the front with respect to the eyeball 1, It is possible to prevent the subject from easily closing the eyelid and to irradiate excitation light toward the sclera 11 of the eyeball 1 satisfactorily. However, the line-of-sight guiding unit 7 may be configured to guide the line of sight in another direction, not limited to the upper side of the eyeball 1 with respect to the front.

  In the present embodiment, only one eyepiece 61 is provided in association with one eye to be measured, and excitation light is irradiated toward the sclera 11 of one eyeball 1 of the subject. It has become so. The line of sight of the one eyeball 1 (the eyeball to be measured) is guided by the line-of-sight guidance unit 7.

  However, the configuration is not limited to this, and the line of sight of the other eyeball (eyeball that is not a measurement target) of the subject may be guided by the line-of-sight guidance unit 7. In this case, the line-of-sight guidance unit 7 may be provided outside the housing 6. Even when the line of sight of the other eyeball of the subject is guided by the line-of-sight guiding unit 7, the line of sight of the one eyeball 1 is also guided in the same direction as the natural eyeball. The line of sight of 1 (the one eyeball) can be guided well.

  Further, the line-of-sight guiding unit 7 is not limited to a structure that continuously guides the subject's line of sight during measurement, and may be configured to guide intermittently. When the line-of-sight guidance unit 7 includes the light source 71 as in this embodiment, the light may adversely affect the measurement depending on the wavelength of the light from the light source 71. Therefore, the light source 71 may be turned on only before the measurement to guide the subject's line of sight, and the light source 71 may be turned off during the measurement.

  Note that, as described above, the line of sight of the other eyeball (eyeball that is not the measurement target) of the subject is guided by the line-of-sight guidance unit 7, and the line-of-sight guidance unit 7 is provided outside the housing 6. In such a case, even if the line-of-sight guiding unit 7 continuously guides the line of sight of the subject during measurement, the light from the light source 71 can be prevented from adversely affecting the measurement.

  The imaging unit 8 images the eyeball 1 from the front of the subject's eyeball 1 (eyeball to be measured), for example. An image picked up by the image pickup unit 8 is displayed on a display unit 9 provided in the fluorescence measuring apparatus. Thus, since the image captured by the imaging unit 8 is displayed on the display unit 9, the operator confirms the state of the eyeball 1 of the subject based on the image displayed on the display unit 9, and appropriately Measurements can be made.

  The fluorescence measuring apparatus is provided with an operation unit 10 for an operator to perform an operation. By operating the operation unit 10, for example, various types of information such as an image captured by the imaging unit 8 and measurement values can be displayed on the display unit 9 and the operation of the apparatus can be instructed. It is preferable that the information displayed on the display unit 9 can be output in various modes such as printing by a printer, storage in a storage medium, and transmission via a network.

  In the present embodiment, the display unit 9 and the operation unit 10 are configured to be provided in the housing 6. However, the configuration is not limited to this, and at least one of the display unit 9 and the operation unit 10 may be provided separately from the housing 6.

  FIG. 3 is a schematic diagram showing a first modification of the configuration of the fluorescence measuring apparatus. In this example, irradiation light from the light source 21 is applied to the sclera 11 of the eyeball 1 through the optical fiber 25, and fluorescence from the sclera 11 is received by the photodetector 34 through the optical fiber 35. It has become. The configurations of the light source 21, the lens 22, the optical filter 23 and the lens 24 in the irradiation mechanism 2, the lens 31, the optical filter 32, the lens 33, the photodetector 34, and the calculation unit 4 in the light receiving mechanism 3 are the same as in the above embodiment. is there.

  The excitation light emitted from the light source 21 is collected by the lens 26 and enters one end of the optical fiber 25. Then, after the excitation light emitted from the other end of the optical fiber 25 is converted into parallel light by the lens 22, unnecessary wavelength light is removed by the optical filter 23, and only the excitation wavelength light is collected by the lens 24. The sclera 11 of the eyeball 1 is irradiated. In this case, the irradiation light guide unit 102 that guides the excitation light emitted from the light source 21 includes an optical system such as the lens 26, the optical fiber 25, the lens 22, the optical filter 23, and the lens 24.

  The light emitted from the irradiation position of the excitation light in the sclera 11 of the eyeball 1 is converted into parallel light by the lens 31 and then only the fluorescence wavelength is transmitted through the optical filter 32. The fluorescence transmitted through the optical filter 32 is collected by the lens 33 and enters one end of the optical fiber 35. The fluorescence emitted from the other end of the optical fiber 35 is collected by the lens 36 and received by the photodetector 34. In this case, the light receiving and guiding unit 103 that guides the light from the eyeball 1 to the photodetector 34 includes an optical system such as the lens 31, the optical filter 32, the lens 33, the optical fiber 35, and the lens 36.

  As described above, by using the optical fibers 25 and 35 as an example of the flexible light guide member, when the irradiation position of the excitation light and the measurement position of the fluorescence in the eyeball 1 are adjusted, the large-scale movement of the component parts is performed. Can be prevented. In other words, while the optical fibers 25 and 35 are deformed, the irradiation position can be obtained by moving only the lens 22, the optical filter 23 and the lens 24 in the irradiation mechanism 2, and the lens 31, the optical filter 32 and the lens 33 in the light receiving mechanism 3. And the measurement position can be adjusted. However, the light guide member having flexibility is not limited to the optical fibers 25 and 35.

  The adjustment of the irradiation position and the measurement position requires very high accuracy, but the position can be adjusted with high accuracy by adopting a configuration that does not involve a large movement of the component parts. It is preferable that the position adjustment is automatically performed in order to improve measurement efficiency. In this case, the configuration may be such that the component is moved by a piezoelectric element or an actuator and the position is adjusted so that the signal from the photodetector 34 becomes maximum. However, the configuration is not limited to this, and a configuration in which the operator manually performs the position adjustment may be employed.

  FIG. 4 is a schematic diagram showing a second modification of the configuration of the fluorescence measuring apparatus. In this example, the optical fiber 25 in FIG. 3 is branched into a first fiber 251 and a second fiber 252 using, for example, a fiber coupler. As a result, the excitation light from the light source 21 is guided separately into the first fiber 251 and the second fiber 252 in the optical fiber 25.

  The excitation light emitted from the first fiber 251 is converted into parallel light by the lens 22, then light having an unnecessary wavelength is removed by the optical filter 23, and only the light having the excitation wavelength is condensed by the lens 24. The sclera 11 is irradiated. Since the structure of the light receiving mechanism 3 for receiving light from the sclera 11 is the same as that in FIG. 3, the same reference numerals are given to the drawings, and detailed description thereof is omitted.

  On the other hand, after the excitation light emitted from the second fiber 252 is converted into parallel light by the lens 22A, the light having an unnecessary wavelength is removed by the optical filter 23A, and only the light having the excitation wavelength is condensed by the lens 24A. The sample 5 is irradiated. Each of these component parts 22 </ b> A to 24 </ b> A preferably has the same configuration as the lens 22, the optical filter 23, and the lens 24 described above.

  The fluorescence from the standard sample 5 is received by the light receiving mechanism 3A. The light receiving mechanism 3A includes a lens 31A, an optical filter 32A, a lens 33A, a photodetector 34A, an optical fiber 35A, a lens 36A, and the like. Each of these component parts 31 </ b> A to 36 </ b> A preferably has the same configuration as the lens 31, the optical filter 32, the lens 33, the photodetector 34, the optical fiber 35, and the lens 36 described above.

  As described above, in the example of FIG. 4, the irradiation light guide unit 102 standardizes the first irradiation light guide unit 121 that guides the excitation light emitted from the light source 21 to the sclera 11 and the excitation light emitted from the light source 21. Branching to the second irradiation light guide part 122 leading to the sample 5. Thereby, excitation light irradiated from the same light source 21 is simultaneously guided to the sclera 11 and the standard sample 5. Therefore, when the excitation light emitted from the light source 21 is unstable, both the fluorescence received light intensity from the standard sample 5 and the fluorescence received light intensity from the sclera 11 vary. Therefore, the calculation unit 4 obtains a more stable measurement value by converting the fluorescence reception intensity from the sclera 11 into a relative measurement value using the fluorescence reception intensity from the standard sample 5 as a reference value. Can do.

  However, the 1st irradiation light guide part 121 and the 2nd irradiation light guide part 122 are not restricted to what is comprised by branching the optical fiber 25, but 1st using the light guide member which has another flexibility. The irradiation light guide unit 121 and the second irradiation light guide unit 122 may be configured. In addition, the first irradiation light guide unit 121 and the second irradiation light guide unit 122 can be configured by using other various components as well as the flexible light guide member.

  FIG. 5 is a schematic diagram showing a third modification of the configuration of the fluorescence measuring apparatus. In this example, among the light from the eyeball 1 guided to the photodetector 34 in FIG. 3, the excitation light (scattered light) scattered by the eyeball 1 is different from the photodetector 34A that receives fluorescence. It is designed to receive light. The configuration of the irradiation mechanism 2 for irradiating the sclera 11 of the eyeball 1 of the subject with the excitation light is the same as that in FIG. To do.

  A part of the light receiving mechanism 3 for receiving light from the sclera 11 is the same as that in the case of FIG. 3, and the same reference numerals are given to the same configurations. Specifically, the lens 31, the optical filter 32, the lens 33, the photodetector 34, and the optical fiber 35 are configured by the same members as in the case of FIG. 3, but their arrangement is partially different. .

  In this example, the optical filter 32 is disposed not between the lens 31 and the lens 33 but between the optical fiber 35 and the photodetector 34. Further, a lens 37 and a half mirror 38 are disposed between the optical fiber 35 and the optical filter 32, and a lens 39 is disposed between the optical filter 32 and the photodetector 34.

  The light emitted from the irradiation position of the excitation light on the sclera 11 of the eyeball 1 is collimated by the lens 31, collected by the lens 33, and incident on one end of the optical fiber 35. The light emitted from the other end of the optical fiber 35 is converted into parallel light by the lens 37, and then a part of the light passes through the half mirror 38 and enters the optical filter 32. Only the fluorescence wavelength is transmitted through the optical filter 32, and the transmitted fluorescence is collected by the lens 39 and received by the photodetector 34. In this case, the light receiving and guiding unit 103 that guides light from the eyeball 1 to the photodetector 34 is provided by an optical system such as the lens 31, the lens 33, the optical fiber 35, the lens 37, the half mirror 38, the optical filter 32, and the lens 39. Composed.

  In the half mirror 38, a part of the light is reflected and guided to the photodetector 34A side. The light reflected by the half mirror 38 enters the optical filter 32A, and only the scattered light having the same wavelength as the excitation light is transmitted through the optical filter 32A. The scattered light transmitted through the optical filter 32A is collected by the lens 39A and received by the photodetector 34A. In this case, the photodetector 34 </ b> A constitutes a scattered light receiving unit that receives the excitation light scattered in the eyeball 1.

  The computing unit 4 can perform computation based on the fluorescence received light intensity at the photodetector 34 and the scattered light received intensity at the photodetector 34A. For example, the calculation unit 4 may be configured to perform a calculation of dividing the fluorescence light reception intensity by the scattered light reception intensity.

  As described above, in the example of FIG. 5, the received light intensity of the fluorescence from the sclera 11 can be corrected using the received light intensity of the scattered light in the photodetector 34A. When the illumination intensity of the excitation light in the eyeball 1 and the light collection efficiency from the eyeball 1 fluctuate due to variations in the positions of the irradiation mechanism 2 and the light receiving mechanism 3 with respect to the eyeball 1 in addition to fluctuations in the intensity of the excitation light emitted from the light source 21. In some cases, the light reception intensity of the fluorescence in the photodetector 34 may fluctuate. In such a case, the received light intensity of the scattered light in the photodetector 34A also varies, so that the received light intensity of the fluorescence from the sclera 11 is corrected using the received light intensity of the scattered light. Thus, a more stable measurement value can be obtained.

  However, the irradiation light guide 102 that guides the excitation light emitted from the light source 21 and the light reception light guide 103 that guides the light from the eyeball 1 to the photodetector 34 are limited to the configuration including the optical fibers 25 and 35. Alternatively, the optical fiber 25 or 35 may not be provided as shown in FIG.

  FIG. 6 is a schematic plan view illustrating an example of the positional relationship between the irradiation light guide unit 102 and the imaging unit 8. FIG. 7 is a view as seen from an arrow A in FIG. 6 and shows an example of the positional relationship between the irradiation light guide 102 and the light receiving light guide 103. 6 and 7, an example of the positional relationship among the irradiation light guide unit 102, the light receiving light guide unit 103, and the imaging unit 8 in the fluorescence measurement device of FIG. However, the configuration illustrated in FIGS. 6 and 7 is not limited to the fluorescence measurement device in FIG. 5 but can be applied to fluorescence measurement devices having other configurations.

  In this example, the optical axis L1 of the excitation light irradiated from the light source 21 to the sclera 11 of the eyeball 1 through the irradiation light guide 102 is relative to the normal L2 at the irradiation center C of the excitation light on the eyeball. Inclined at a predetermined angle α around the irradiation center C. Specifically, the excitation light is emitted toward the irradiation center C located at the apex on the front side of the eyeball 1 from a direction inclined by an angle α of 30 to 60 ° from the normal L2 toward the outer corner of the eye. Yes. On the other hand, the imaging unit 8 is located on the normal line L2.

  The optical axis L3 of the light guided from the eyeball 1 to the light receiving / guiding unit 103 is perpendicular to the plane passing through the optical axis L1 and the optical axis L2 with respect to the optical axis L1 (the backward direction in FIG. 6). , In the downward direction in FIG. 7, is inclined at a predetermined angle β around the irradiation center C. This angle β is preferably as small as possible. Moreover, it can be set as an optimal measurement position by adjusting so that the optical axis L3 may cross | intersect the optical axis L1 on an eyeball surface.

  When the irradiation range of the excitation light and the measurement range (collection range) of the fluorescence in the eyeball 1 are set to the same level, the fluorescence is only shifted slightly with respect to the optimum measurement position. The received light intensity of the light changes greatly. Therefore, the luminous flux diameter D1 of the excitation system corresponding to the optical axis L1 at the intersection position of the optical axis L1 and the optical axis L3 is preferably larger than the luminous flux diameter D2 of the observation system corresponding to the optical axis L3 at the intersection position. . In this case, for example, the light beam diameter D1 may be 2 to 4 mm, and the light beam diameter D2 may be 1 to 3 mm.

  If such a positional relationship is adopted, even if there is another member such as the imaging unit 8 in the normal L2 direction at the irradiation center C of the excitation light on the eye sphere as shown in FIG. On the side, the excitation light can be irradiated from a position relatively close to the eyeball 1. Thereby, the illumination intensity of the excitation light in the eyeball 1 can be raised and the sensitivity of measurement can be improved.

  As shown in FIG. 6, the excitation light from the light source 21 is preferably emitted from the outer corner of the eyeball 1. Further, as shown in FIG. 7, the fluorescence from the sclera 11 is preferably measured on the lower side than the front with respect to the eyeball 1. This can prevent the eyelashes from interfering with the passage of excitation light and fluorescence, thereby improving measurement accuracy. In this case, as shown in FIG. 7, the configuration is such that the fluorescence from the sclera 11 is measured on the outer corner of the eyeball 1, so that the excitation light specularly reflected by tears on the eyeball 1 is light. Since it is possible to prevent the detector 34A from receiving the light, the measurement accuracy can be further improved.

  However, the position of the irradiation center C of the excitation light and the direction of the optical axis L1, the measurement position of the fluorescence and the direction of the optical axis L3, and the angles α and β are not limited to the above modes.

  FIG. 8 is a schematic diagram showing a fourth modification of the configuration of the fluorescence measuring apparatus. In this example, the fluorescence light receiving unit that receives the fluorescence from the sclera 11 irradiated with the excitation light is configured by an imaging unit 8 that images the eyeball 1 of the subject. As in the case of FIG. 2, the imaging unit 8 is disposed in front of the eyeball 1 of the subject, for example. About the structure similar to FIG. 2, the same code | symbol is attached | subjected to a figure and detailed description is abbreviate | omitted.

  In the housing 6, for example, a visible light source 21A, an ultraviolet light source 21B, an optical filter 32, and the like are provided. The visible light source 21A and the ultraviolet light source 21B irradiate light toward the eyeball 1 of the subject positioned in the eyepiece 61. The visible light source 21A irradiates visible light, and the ultraviolet light source 21B irradiates ultraviolet light. . As the imaging unit 8, one having sensitivity to the wavelength of visible light is used.

  The optical filter 32 can be inserted and removed between a position indicated by a solid line in FIG. 8 and a position indicated by a two-dot chain line. The optical filter 32 is located between the sclera 11 of the eyeball 1 and the imaging unit 8 (the optical path of the imaging unit 8) at the position indicated by the solid line in FIG. 8 and transmits only fluorescence from the sclera 11. Let On the other hand, at the position indicated by the two-dot chain line in FIG. 8, the optical filter 32 is retracted from the optical path of the imaging unit 8.

  At the time of preparation before measurement, the visible light source 21 </ b> A is turned on, and the optical filter 32 is retracted from the optical path of the imaging unit 8. By displaying an image captured by the imaging unit 8 in this state on the display unit 9, the operator can confirm the state of the eyeball 1 of the subject. Thereafter, when performing fluorescence measurement, the visible light source 21A is turned off, the ultraviolet light source 21B is turned on, and the optical filter 32 is inserted into the optical path of the imaging unit 8. Thereby, the fluorescence from the sclera 11 is made incident on the imaging unit 8, and calculation is performed by the calculation unit 4 based on the received light intensity obtained from the image (fluorescence image) captured by the imaging unit 8.

  However, when a light source that emits visible light that does not include the fluorescence wavelength of AGEs is used as the visible light source 21A, the visible light source is blocked by the optical filter 32 by preventing the visible light from entering the imaging unit 8. Fluorescence measurement can be performed even when 21A is kept on. Further, in order to avoid unnecessary exposure to ultraviolet light, it is preferable to turn off the ultraviolet light source 21B except during fluorescence measurement. However, if the amount of ultraviolet light is less than the allowable value for exposure to ultraviolet light, the ultraviolet light source may be used during preparation before measurement. 21B may remain on. In this case, if the imaging unit 8 having sensitivity to the wavelength of the ultraviolet rays is used, the ultraviolet rays from the ultraviolet light source 21 </ b> B are used as illumination, and the scattered light and reflected light are captured by the imaging unit 8 without passing through the optical filter 32. Images can be obtained.

  The optical filter 32 is not limited to a configuration that can be retracted from the optical path of the imaging unit 8, and may be always disposed on the optical path. For example, when the wavelength of ultraviolet light emitted from the ultraviolet light source 21B is 365 nm, the fluorescence from the sclera 11 becomes visible light having a wavelength of about 470 nm. If the visible light from the visible light source 21A is light (for example, blue light) having a wavelength that can be transmitted through the optical filter 32, the visible light source 21A can be used without retracting the optical filter 32 from the optical path of the imaging unit 8. The imaging unit 8 can capture images. In this case, since it is not necessary to retract the optical filter 32, the structure can be further simplified.

  FIG. 9 is a schematic diagram illustrating an example of an image captured by the imaging unit 8 of FIG. As shown in FIG. 8, the standard sample 5 is provided around the eyepiece 61. The standard sample 5 is provided around the eyeball 1 in the imaging region 81 of the imaging unit 8. That is, the standard sample 5 has an opening 51 at the center, and the standard sample 5 is provided so that at least a part of the eyeball 1 is exposed from the opening 51.

  In the example of FIGS. 8 and 9, the fluorescence light receiving unit that receives the fluorescence from the sclera 11 is configured by the imaging unit 8 that images the eyeball 1 of the subject. Can be reduced. In addition, since the standard sample 5 is provided around the eyeball 1 in the imaging region 81 of the imaging unit 8, fluorescence from both the sclera 11 and the standard sample 5 can be simultaneously imaged. A well-stable measurement value can be obtained.

  FIG. 10 is a schematic diagram showing a fifth modification of the configuration of the fluorescence measuring apparatus. In this example, the branch light guide 104 is branched from the light receiving light guide 103 that guides the light from the eyeball 1 to the photodetector 34 in FIG. In addition, a light source 141 for allowing adjustment light to enter the branch light guide unit 104 is provided. The configuration of the irradiation mechanism 2 for irradiating the sclera 11 of the eyeball 1 of the subject with the excitation light is the same as that in FIG. To do.

  In this example, the optical fiber 35 in FIG. 3 is branched into a first fiber 351 and a second fiber 352 using, for example, a fiber coupler. The fluorescence from the sclera 11 is received by the photodetector 34 through the first fiber 351. On the other hand, the second fiber 352 constitutes the branch light guide unit 104 together with the lens 142.

  The light source 141 constitutes an adjustment irradiation unit that irradiates the eyeball 1 with adjustment light from the branch light guide unit 104 via the light reception light guide unit 103. That is, the adjustment light from the light source 141 is collected by the lens 142 and incident on the end of the second fiber 352, and the light emitted from the opposite end of the optical fiber 35 is applied to the eyeball 1. It has become so.

  As described above, in the example of FIG. 10, the adjustment light can be applied to the eyeball 1 via the light receiving and guiding unit 103 that guides the light from the eyeball 1 to the photodetector 34. Therefore, by confirming the irradiation position of the adjustment light on the eyeball 1, the position on the eyeball 1 where the light is received by the photodetector 34 can be recognized. Accordingly, the position of the optical system can be adjusted while confirming the irradiation position of the adjustment light, and the fluorescence can be received by the photodetector 34 at an appropriate position, so that the measurement accuracy can be improved.

  From the viewpoint of efficiently receiving weak fluorescence by the photodetector 34, it is preferable that the lens 31 is disposed close to the eyeball 1 in a range that does not contact the eyeball 1 or the eyelashes. In this case, since the numerical aperture of the lens 31 increases and the focal point suddenly blurs when the lens 31 deviates from the in-focus position, it is difficult to determine the focal position of the adjustment light from the image captured by the imaging unit 8. Become. Therefore, in the example of FIG. 10, an optical aperture 143 is provided in the optical path of the adjustment light so that the optical path of the adjustment light can be reduced and the numerical aperture can be reduced. In the fluorescence measurement, the optical diaphragm 143 is expanded to perform the measurement.

  However, the branch light guide unit 104 is not limited to the one configured by branching the optical fiber 35, and the branch light guide unit 104 may be configured using another flexible light guide member. In addition, the branched light guide unit 104 can be configured by using other various components as well as the flexible light guide member.

  FIG. 11 is a diagram for describing an aspect when adjusting the position of the optical system in the fluorescence measurement apparatus of FIG. 10, and shows an example of an image in the imaging region 81 captured by the imaging unit 8 during the adjustment. ing. In this example, the case where the configuration shown in FIG. 10 is used in the arrangement of the optical system shown in FIGS. 6 and 7 will be described.

  When adjusting the position of the optical system, first, the center position 12 of the eyeball 1 is detected by processing and analyzing the image of the eyeball 1 imaged by the imaging unit 8. In this example, as shown in FIG. 11A, the excitation light irradiation spot 13 irradiated from the light source 21 toward the eyeball 1 and the adjustment light irradiated from the light source 141 toward the eyeball 1. The irradiation spots 14 are all shifted from the center position 12.

  In this state, when the optical system of the irradiation light guide unit 102 is moved in the front-rear direction with respect to the eyeball 1, the irradiation spot 13 of the excitation light moves in the direction indicated by the broken line 13A in the drawing. On the other hand, when the optical system of the light receiving / guiding unit 103 is moved in the front-rear direction with respect to the eyeball 1, the adjustment light irradiation spot 14 moves in the direction indicated by the broken line 14A in the drawing. Therefore, by appropriately moving the optical systems of the irradiation light guide 102 and the light receiving light guide 103 in the front-rear direction, as shown in FIG. 11B, the irradiation spots 13, 14 are overlapped. be able to.

  Thereafter, from the state shown in FIG. 11B, by appropriately moving the optical systems of the irradiation light guide 102 and the light receiving light guide 103 in the vertical direction and the horizontal direction, as shown in FIG. Each irradiation spot 13, 14 can be made to coincide with the center position 12 of the eyeball 1. Since the eyeball 1 is spherical, when the optical systems of the irradiation light guide 102 and the light receiving light guide 103 are moved in the vertical direction and the horizontal direction, the overlapping state of the irradiation spots 13 and 14 also changes. By performing the adjustment by repeating coarse adjustment and fine adjustment, a state as shown in FIG. 11C can be obtained.

  The adjustment light from the light source 141 is turned on only during adjustment, and is turned off after adjustment to perform fluorescence measurement. However, when the wavelength of the adjustment light emitted from the light source 141 is a wavelength that does not affect the fluorescence measurement, the fluorescence measurement can be performed with the adjustment light on.

  FIG. 12 is a schematic diagram illustrating a sixth modification of the configuration of the fluorescence measuring apparatus. In this example, the light for adjustment is guided to the eyeball 1 from the light source 141 for irradiating the eyeball 1 with the light for adjustment via the light guide for adjustment 105 provided separately from the light receiving light guide 103. It has come to be. The adjustment light guide unit 105 includes, for example, an optical fiber 151, a collimator lens 152, an optical aperture 153, and the like, and adjustment light from the light source 141 is applied to the eyeball 1 as a thin light beam having a small divergence angle. It has come to be.

  The adjustment light guide 105 is movable together with the optical system of the light receiving light guide 103. The optical axis L4 of the adjustment light is an irradiation center in a direction perpendicular to the normal line L2 at the irradiation center C of the excitation light on the ocular surface with respect to the plane passing through the optical axis L1 and the optical axis L2 in FIG. It is inclined downward at a predetermined angle γ with C as the center.

  As described above, in the example of FIG. 12, the adjustment light can be applied to the eyeball 1 from the adjustment light guide 105 through the adjustment light guide 105 provided separately from the light reception light guide 103. it can. In the case of the configuration in which the branch light guide unit 104 is provided as shown in FIG. 10, a part of the light from the eyeball 1 that is guided to the photodetector 34 side at the time of measurement is also guided to the branch light guide unit 104. Although the light receiving intensity at the photodetector 34 is reduced, if the adjustment light guide unit 105 is provided separately as in this example, the light receiving intensity at the photodetector 34 is prevented from decreasing and the measurement sensitivity is improved. be able to.

  FIG. 13 is a diagram for explaining an aspect when adjusting the position of the optical system in the fluorescence measurement apparatus of FIG. 12, and shows an example of an image in the imaging region 81 captured by the imaging unit 8 during the adjustment. ing. In this example, a case where the configuration as shown in FIG. 12 is used in the arrangement of the optical system as shown in FIGS. 6 and 7 will be described.

  When adjusting the position of the optical system, first, the center position 12 of the eyeball 1 is detected by processing and analyzing the image of the eyeball 1 imaged by the imaging unit 8. In this example, as illustrated in FIG. 13A, the excitation light irradiation spot 13 irradiated from the light source 21 toward the eyeball 1 and the adjustment light irradiated from the light source 141 toward the eyeball 1. All the irradiation spots 15 are shifted from the center position 12.

  When the optical system of the irradiation light guide unit 102 is moved in the front-rear direction with respect to the eyeball 1, the irradiation spot 13 of the excitation light moves in the direction indicated by the broken line 13A in the drawing. On the other hand, when the optical system of the light receiving light guide 103 is moved in the front-rear direction with respect to the eyeball 1 together with the adjustment light guide 105, the adjustment light irradiation spot 15 is indicated by a broken line 15A in the figure. Move in the direction.

  Prior to such movement of the optical systems of the irradiation light guide 102 and the light receiving light guide 103 in the front-rear direction, in this example, each optical system is appropriately moved in the vertical direction and the left-right direction as shown in FIG. As shown in b), an intersection of a horizontal line passing through the excitation light irradiation spot 13 and a vertical line passing through the adjustment light irradiation spot 15 overlaps the center position 12.

  After that, by appropriately moving the optical systems of the irradiation light guide 102 and the light receiving light guide 103 in the front-rear direction from the state shown in FIG. 13B, as shown in FIG. The irradiation spots 13 and 15 can be overlapped with each other. However, the position of the optical system can be adjusted in the same manner as in the case of FIG.

  The adjustment light emitted from the light source 141 to the eyeball 1 through the adjustment light guide unit 105 is turned on only during adjustment, and is turned off after adjustment to perform fluorescence measurement. However, when the wavelength of the adjustment light emitted from the light source 141 is a wavelength that does not affect the fluorescence measurement, the fluorescence measurement can be performed with the adjustment light on.

  FIG. 14 is a schematic diagram illustrating a configuration example of a fluorescence measuring apparatus according to another embodiment. The fluorescence measurement device according to the present embodiment is not a desktop type, but a handy type fluorescence measurement device that is used while being held by an operator. For this reason, the housing 6 is formed with a gripping portion 63 for the operator to grip. About the structure similar to FIG. 8, the same code | symbol is attached | subjected to a figure and detailed description is abbreviate | omitted.

  The housing 6 is provided with an operation display unit 91 configured by, for example, a liquid crystal display provided with a touch panel. The operator can operate the operation display unit 91 with the other hand while holding the grip unit 63 with one hand and confirming the captured image of the imaging unit 8 displayed on the operation display unit 91. . Thus, although the operation part and the display part may be comprised integrally as the operation display part 91, you may comprise separately.

  However, the handy-type fluorescence measuring apparatus according to the present embodiment is not limited to a configuration in which the operator must use both hands, and may be configured so that the operator can use it with one hand. In this case, an operation unit that can be operated by a hand that the operator holds the grip portion 63 may be provided in the grip portion 63. For example, an operation unit for instructing a relatively simple operation such as an operation for instructing imaging by the imaging unit 8 (shutter operation) or the like is performed by the operator's finger (thumb or index finger) holding the grip unit 63. Etc.) may be provided.

  Unlike the desktop type, the handheld fluorescence measuring apparatus as in the present embodiment does not occupy the mounting table T and is easy to carry. In addition, when using a hand-held fluorescence measuring device, the posture of the subject is not limited, and thus, for example, a subject who is lying down can easily perform measurement.

  Image data captured by the imaging unit 8 can be output to the outside from the fluorescence measurement device by wireless or wired communication. The output image data can be used, for example, for image processing calculation in a personal computer or stored as data, and can also be used for integration or cooperation with a medical record or database.

  Generally, a high processing capability is required for an arithmetic unit for performing image processing. Therefore, by performing the image processing calculation with an external personal computer, the configuration of the fluorescence measuring apparatus can be simplified and the manufacturing cost can be reduced. In the case of a fluorescence measuring apparatus driven by a battery, the power consumption of the battery can be reduced and the driving time can be extended.

  In the above embodiment, the specific configuration of the fluorescence measurement device according to an embodiment of the present invention has been described. However, a fluorescence measurement method is provided by using at least a part of the configuration exemplified in the fluorescence measurement device. It is also possible to do. In this case, the fluorescence measurement method irradiates excitation light toward the sclera 11 of the eyeball 1 of the subject (excitation light irradiation step), receives fluorescence from the sclera 11 (fluorescence light reception step), and The configuration may be such that measurement can be performed by performing a calculation based on the received light intensity (calculation step).

DESCRIPTION OF SYMBOLS 1 Eyeball 2 Irradiation mechanism 3 Light reception mechanism 4 Calculation part 5 Standard sample 6 Case 7 Gaze guidance part 8 Imaging part 9 Display part 10 Operation part 11 Sclera 21 Light source 22 Lens 23 Optical filter 24 Lens 25 Optical fiber 26 Lens 31 Lens 32 Optical filter 33 Lens 34 Photo detector 35 Optical fiber 36 Lens 37 Lens 38 Half mirror 39 Lens 61 Eyepiece 62 Contact surface 63 Gripping part 71 Light source 72 Lens 91 Operation display part 102 Irradiation light guide part 103 Light reception light guide part 104 Branch light guide unit 105 Adjustment light guide unit 121 First irradiation light guide unit 122 Second irradiation light guide unit 141 Light source 142 Lens 151 Optical fiber 152 Collimator lens L2 Normal line T Mounting table

Claims (13)

An excitation light irradiation unit that emits excitation light that can emit fluorescence from the sclera toward the sclera of the subject's eyeball,
A fluorescence light receiving unit that receives fluorescence from the sclera irradiated with excitation light; and
A fluorescence measuring apparatus comprising: an arithmetic unit that performs an operation based on a light reception intensity in the fluorescence light receiving unit.   The fluorescence measuring apparatus according to claim 1, further comprising a line-of-sight guiding unit for guiding the line of sight of the subject in a direction different from the incident direction of the excitation light. An irradiation light guide for guiding excitation light emitted from the excitation light irradiation unit to a standard sample having known fluorescence characteristics,
3. The fluorescence according to claim 1, wherein the calculation unit performs a calculation based on the fluorescence from the sclera received by the fluorescence light receiving unit and the received light intensity of the fluorescence from the standard sample. measuring device.   The irradiation light guide unit includes a first irradiation light guide unit that guides excitation light irradiated from the excitation light irradiation unit to the sclera, and a second unit that guides excitation light irradiated from the excitation light irradiation unit to the standard sample. The fluorescence measuring apparatus according to claim 3, wherein the fluorescence measuring apparatus is branched into an irradiation light guide unit. Further comprising a scattered light receiving unit for receiving excitation light scattered in the eyeball,
The fluorescence measuring device according to any one of claims 1 to 4, wherein the calculation unit performs a calculation based on a light reception intensity in the fluorescence light reception unit and a light reception intensity in the scattered light reception unit.   The said excitation light irradiation part irradiates excitation light at an angle of 30-60 degrees with respect to the normal line in the irradiation center of the excitation light on an eye spherical surface. Fluorescence measuring device. An imaging unit for imaging the eyeball of the subject;
The fluorescence measuring apparatus according to claim 1, further comprising a display unit that displays an image captured by the imaging unit. The fluorescent light receiving unit is configured by an imaging unit that images the eyeball of the subject,
The fluorescence measuring apparatus according to claim 1, wherein the calculation unit performs a calculation based on a received light intensity obtained from an image captured by the imaging unit. A light receiving light guide that guides light from the eyeball to the fluorescent light receiving unit;
A branched light guide part branched from the light receiving light guide part;
The fluorescence measurement according to claim 1, further comprising: an adjustment irradiation unit that irradiates the eyeball with adjustment light from the branch light guide unit through the light reception light guide unit. apparatus. A light receiving light guide that guides light from the eyeball to the fluorescent light receiving unit;
An adjustment irradiator that irradiates the eyeball with adjustment light; and
The adjustment light guide unit that is provided separately from the light receiving light guide unit and guides the adjustment light from the adjustment irradiation unit to an eyeball. The fluorescence measuring apparatus as described. A housing for accommodating the excitation light irradiation unit and the fluorescence light receiving unit;
The fluorescence measuring apparatus according to claim 1, wherein the casing is provided with a contact surface that contacts the mounting table when the casing is mounted. A housing for accommodating the excitation light irradiation unit and the fluorescence light receiving unit;
The fluorescence measuring apparatus according to claim 1, wherein the casing is provided with a grip portion for an operator to grip. An excitation light irradiation step of irradiating excitation light capable of emitting fluorescence from the sclera toward the sclera of the eyeball of the subject from the excitation light irradiation unit;
A fluorescence receiving step for receiving fluorescence from the sclera irradiated with excitation light by a fluorescence receiving unit;
And a calculation step of performing a calculation in the calculation unit based on the received light intensity in the fluorescence light receiving unit.

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