WO2013038242A1 - Method for spatially measuring tissue structures - Google Patents

Method for spatially measuring tissue structures Download PDF

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Publication number
WO2013038242A1
WO2013038242A1 PCT/IB2012/001670 IB2012001670W WO2013038242A1 WO 2013038242 A1 WO2013038242 A1 WO 2013038242A1 IB 2012001670 W IB2012001670 W IB 2012001670W WO 2013038242 A1 WO2013038242 A1 WO 2013038242A1
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Prior art keywords
organ
probe
tissue structures
reference probe
measuring
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PCT/IB2012/001670
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German (de)
French (fr)
Inventor
Zoran Djinovic
Milos Tomic
Marljana STOJKOVIC
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Ima Integrated Microsystems Austria Gmbh
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Publication of WO2013038242A1 publication Critical patent/WO2013038242A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6802Sensor mounted on worn items
    • A61B5/6803Head-worn items, e.g. helmets, masks, headphones or goggles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/1005Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for measuring distances inside the eye, e.g. thickness of the cornea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/102Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for optical coherence tomography [OCT]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0066Optical coherence imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1072Measuring physical dimensions, e.g. size of the entire body or parts thereof measuring distances on the body, e.g. measuring length, height or thickness
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1075Measuring physical dimensions, e.g. size of the entire body or parts thereof for measuring dimensions by non-invasive methods, e.g. for determining thickness of tissue layer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02015Interferometers characterised by the beam path configuration
    • G01B9/02017Interferometers characterised by the beam path configuration with multiple interactions between the target object and light beams, e.g. beam reflections occurring from different locations
    • G01B9/02021Interferometers characterised by the beam path configuration with multiple interactions between the target object and light beams, e.g. beam reflections occurring from different locations contacting different faces of object, e.g. opposite faces
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02015Interferometers characterised by the beam path configuration
    • G01B9/02025Interference between three or more discrete surfaces
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02015Interferometers characterised by the beam path configuration
    • G01B9/02027Two or more interferometric channels or interferometers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/0209Low-coherence interferometers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/0209Low-coherence interferometers
    • G01B9/02091Tomographic interferometers, e.g. based on optical coherence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/16Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for measuring intraocular pressure, e.g. tonometers
    • A61B3/165Non-contacting tonometers

Definitions

  • the invention relates to a method for spatially measuring a plurality of successive biological tissue structures in an organ, in particular in an eye obtained by evaluating interferograms, from reflected, low-coherent light from a reference probe directed to a reference probe and at least one measuring probe ,
  • the invention further relates to a device for carrying out this method.
  • IOP intraocular pressure
  • interferometric methods in which the spatial extent or thicknesses and spacings of reflective surfaces, e.g. the cornea and the lens are measured by means of an interferometer.
  • the eye to be examined is positioned at a defined distance from a measuring probe, generally a measuring light guide, and coherent light is transmitted through this measuring probe and through a reference probe or a reference light guide directed to a reference reflector in the interferometer. directed.
  • the coherent light from the measuring probe or measuring light guide is reflected at the different structures and the superimposition of the reflected light leads to interference patterns due to the different path lengths which the coherently emerging light from the probes or light guides has to travel back to the respective reflecting structures. which can be evaluated with conventional mathematical algorithms to determine the distances of the reflective structures to each other.
  • the reference probe was directed to a reflector in the interferometer and the superimposition of the reflected light from the probe was via relatively complicated and large-scale devices with lenses and semi-transparent mirrors, which is why the corresponding devices in the practice were used stationary.
  • the intraocular pressure and thus the spatial extent of the tissue structures to be examined which allow a conclusion on the intraocular pressure vary so much in one and the same patient depending on the time of day and the physical activity that a single measurement of spatial Extension or the relative position of the relevant structures does not allow a satisfactory conclusion about the actual physiological conditions.
  • the invention is therefore based on the object of specifying a method with which a spatial measurement of a plurality of biological tissue structures in an organ by means of interferometry can be carried out continuously and over a longer period by means of mobile devices.
  • the method of the type mentioned above is characterized in that, when the spatial extent of a first tissue structure of the organ is known, both the reference probe and the at least one measuring probe are directed onto the organ, the path difference between the two both probes is kept constant.
  • a first tissue structure of the organ is therefore measured and determined with respect to its spatial extent before the actual measurement. For example, the thickness of the cornea, which remains practically constant even with fluctuating intraocular pressure, is suitable for this purpose.
  • both the reference probe and the probe are directed to the organ and the path difference between the two probes is kept constant.
  • the path difference between see the two probes or optical fibers is always meant as a distance in the axial direction, ie in the direction of the path of the light or the electromagnetic reference and measurement signal.
  • one of the biological tissue structures to be measured itself serves as a quasi reference reflector, so that a complex arrangement of lenses and semi-transparent mirrors in the interferometer is no longer necessary. Even a varying distance between the two probes and the tissue structures to be measured does not hinder a precise measurement of the respective spatial extent, so that no apparatus precautions must be taken to keep the eye at a suitable distance.
  • the expenditure on equipment of an interferometer can be considerably reduced so that apart from the reference and measuring probes, only one arithmetic unit with a corresponding program logic is necessary in order to be able to process and store the measured data.
  • the method is developed such that the path difference between the reference probe and the at least one measuring probe is adjusted and fixed to the organ to be measured such that the interference bands corresponding to the first tissue structure in a coupling curve, the known spatial extent of this structure specify, preferably in the interferogram associated with the other tissue structures to be measured interference bands and the actual distances of the other tissue structures are determined relative to the distance of the first tissue structure corresponding interference bands.
  • a coupling curve is understood in the art of fiber optics that signal of a photodiode, in which the interference patterns are reflected in the AC component of the signal. This signal is obtained by varying the optical wavelength in a fiberoptic component Michelson interferometer (Fiber Optics Essentials, K.
  • the distances of the respective biological tissue structures from each other can be directly determined and recorded in order to subsequently be used for diagnosis.
  • the interferograms obtained can have interference bands for different tissue structures.
  • the method according to the invention has been used to measure, for example, the mean corneal thickness (CCT), the anterior chamber depth (ACD) and the length of the eyeball (axial length, AL). All of these values can be correlated with intraocular pressure and thus taken into account in the medical diagnosis.
  • the interference bands have the basic shape of a Gaussian bell curve and have a certain width, referred to as the "dynamic rank", depending on the coherence length of the light used.
  • the invention is therefore preferred further developed that the exact positions of the interference bands are determined by distance determination of the maxima of the Gaussian envelopes of the interference bands.
  • the measured data determined over a certain period of time are used to calculate the relative movements of the plurality of tissue structures of the organ relative to one another. The treating physician can then determine the course of intraocular pressure over the period in question and receive appropriate information for the indicated treatment.
  • the reference light guide and the measuring light guide only one-dimensional length information can be obtained.
  • the invention is developed to advantage in that a plurality of arranged in the form of an array probes are used and activated by an electronic circuit sequentially for the determination of measurement data. Due to the extremely short time required for a spatial measurement or length determination, a corresponding number of measurements can be made in a very short time, with appropriate wiring of the light guides or probes arranged next to each other on the array, so that practically a snapshot of the relevant Organ in the sense of a spatial, three-dimensional survey at a given time can be created.
  • the device for carrying out the method according to the invention is characterized in that reference and measuring probes of an interferometer are fixed to a holder that is portable by a patient and are connected to a portable computing unit.
  • the patient thus carries the arithmetic unit and the holder with him, wherein the holder may be formed, for example in the form of glasses.
  • the holder preferably has means for setting and fixing the path difference between the reference probe and the at least one measuring probe to the organ to be measured.
  • FIG. 1 shows the basic arrangement of the reference and measuring probes
  • FIG. 2 shows a coupling curve as obtained in the method according to the invention
  • FIG. 3 shows a curve indicating the changes of a measured value over time
  • FIG. 4 shows a representation of an application example the invention.
  • 1 denotes an eye as an organ to be measured, the anterior chamber 4 being delimited by the lens 2 and the cornea 3.
  • the distance between the lens 2 and the cornea 3 is subject to measurable fluctuations with changing intraocular pressure and can thus be used to determine the intraocular pressure, which is an important diagnostic indicator in connection with glaucoma.
  • two light guides 6 and 7 are now fixed to a holder 8 (not shown) at a distance D to the organ to be examined which is adjustable and fixable.
  • 9 with an unspecified light guide is referred to, which directs the reflected light from the optical fibers 6 and 7 to a computing unit, also not shown.
  • interference bands 14 result, with a suitable setting of ⁇ L the distance X between the third and the fourth band regardless of the distance D corresponds to the average thickness of the cornea 3 and the Cornea representing glass plate 11.
  • the distance Y between the fourth and the sixth interference band corresponds to the spatial extent 5 of the anterior chamber 4. If there are other structures which reflect light, such as a retina (not shown) in an eye, then further interference bands would be displayed which represent the distance specify the retina to the other structures.
  • FIG. 3 now shows a graph of the values for the spatial extent 5 of the anterior chamber 4 and it can be seen that it is subject to fluctuations over time.
  • Fig. 4 it can be seen that the method according to the present invention can be applied to an interferometer in which a holder 8 carries the optical fibers 6 and 7, wherein the optical fibers 6 and 7 are fed to a computing unit 15 in which the evaluation the interference pattern takes place.
  • a portable measuring device has been provided which allows continuous measurement of the spatial extent of biological tissue structures.

Abstract

The invention relates to a method for spatially measuring a plurality of biological tissue structures that lie one behind the other in an organ, particularly in an eye (1), by evaluating interferograms that are obtained from reflected coherent light from a reference probe (6) directed at a reference reflector (3), and from at least one measurement probe (7). For a known spatial extension of a first tissue structure of the organ, both the reference probe and the at least one measurement probe are directed at said organ, wherein the path difference (ΔL) between these two probes is kept constant.

Description

Verfahren zum räumlichen Vermessen von Gewebestrukturen Method for the spatial measurement of tissue structures
Die Erfindung betrifft ein Verfahren zum räumlichen Vermessen einer Mehrzahl von hintereinander liegenden biologischen Gewe- bestrukturen in einem Organ, insbesondere in einem Auge, durch Auswertung von Interferogrammen erhalten, aus reflektiertem, niedrig-kohärentem Licht aus einer auf einen Referenzreflektor gerichteten Referenzsonde und zumindest einer Messsonde. Die Erfindung betrifft weiters eine Vorrichtung zur Durchführung dieses Verfahrens. The invention relates to a method for spatially measuring a plurality of successive biological tissue structures in an organ, in particular in an eye obtained by evaluating interferograms, from reflected, low-coherent light from a reference probe directed to a reference probe and at least one measuring probe , The invention further relates to a device for carrying out this method.
In der Ophthalmologie werden beispielsweise zur Früherkennung von Glaukom biometrische Messungen am Auge vorgenommen, aus denen Rückschlüsse auf den Augeninnendruck (intraocular pres- sure, IOP) gewonnen werden können. Stand der Technik sind hierbei u.a. interferometrische Verfahren, bei denen die räumliche Erstreckung bzw. die Dicken und Abstände von reflektierenden Oberflächen wie z.B. der Cornea und der Linse mit Hilfe eines Interferometers gemessen werden. Bei der herkömmlichen Interfe- rometrie wird das zu untersuchende Auge in einem definierten Abstand zu einer Messsonde, im allgemeinen ein Messlichtleiter, positioniert und kohärentes Licht wird durch diese Messsonde und durch eine Referenzsonde bzw. einen Referenzlichtleiter, der auf einen Referenzreflektor im Interferomenter gerichtet ist, geleitet. Das kohärente Licht aus der Messsonde bzw. Messlichtleiter wird an den unterschiedlichen Strukturen reflektiert und die Überlagerung des reflektierten Lichts führt durch die unterschiedlichen Weglängen, die das kohärent aus den Sonden bzw. Lichtleitern austretende Licht bis zu den jeweiligen reflektierenden Strukturen zurückzulegen hat, zu Interferenzmustern, die mit herkömmlichen mathematischen Algorithmen ausgewertet werden können, um die Abstände der reflektierenden Strukturen zueinander zu bestimmen. In ophthalmology, for example, biometrical measurements on the eye are made for the early detection of glaucoma, from which conclusions about the intraocular pressure (IOP) can be obtained. State of the art here u.a. interferometric methods in which the spatial extent or thicknesses and spacings of reflective surfaces, e.g. the cornea and the lens are measured by means of an interferometer. In conventional interferometry, the eye to be examined is positioned at a defined distance from a measuring probe, generally a measuring light guide, and coherent light is transmitted through this measuring probe and through a reference probe or a reference light guide directed to a reference reflector in the interferometer. directed. The coherent light from the measuring probe or measuring light guide is reflected at the different structures and the superimposition of the reflected light leads to interference patterns due to the different path lengths which the coherently emerging light from the probes or light guides has to travel back to the respective reflecting structures. which can be evaluated with conventional mathematical algorithms to determine the distances of the reflective structures to each other.
BESTÄTIGUNGSKOPIE Im Stand der Technik wurde, wie bereits erwähnt, die Referenz- ^sonde auf einen Reflektor im Interferometer gerichtet und die Überlagerung des reflektierten Lichts aus der Messsonde erfolgte über relativ komplizierte und groß bauende Vorrichtungen mit Linsen und halb durchlässigen Spiegeln, weshalb die entsprechenden Geräte in der Praxis stationär angewendet wurden. Es ist jedoch bekannt, dass der Augeninnendruck und damit verbunden die räumliche Erstreckung der zu untersuchenden Gewebestrukturen, die einen Rückschluss auf den Augeninnendruck ermöglichen, bei ein und demselben Patienten abhängig von der Tageszeit und der körperlichen Aktivität so stark variieren, dass eine einmalige Messung der räumlichen Erstreckung bzw. der relativen Position der relevanten Strukturen keine zufrieden stellende Aussage über die tatsächlichen physiologischen Gege- benheiten zulässt. Vielmehr wäre es wünschenswert, eine kontinuierliche räumliche Vermessung der relevanten biologischen Gewebestrukturen in einem Organ wie beispielsweise dem Auge über einen längeren Zeitraum durchzuführen, um ein umfassenderes Bild von den physiologischen Gegebenheiten zu erhalten. Dies war aber aufgrund des Umstands, dass die entsprechenden Messgeräte, nämlich die Interferometer, eine erhebliche Baugröße aufwiesen, bisher praktisch nicht durchführbar. CONFIRMATION COPY In the prior art, as already mentioned, the reference probe was directed to a reflector in the interferometer and the superimposition of the reflected light from the probe was via relatively complicated and large-scale devices with lenses and semi-transparent mirrors, which is why the corresponding devices in the practice were used stationary. However, it is known that the intraocular pressure and thus the spatial extent of the tissue structures to be examined, which allow a conclusion on the intraocular pressure vary so much in one and the same patient depending on the time of day and the physical activity that a single measurement of spatial Extension or the relative position of the relevant structures does not allow a satisfactory conclusion about the actual physiological conditions. Rather, it would be desirable to carry out a continuous spatial survey of the relevant biological tissue structures in an organ such as the eye over a longer period of time in order to obtain a more comprehensive picture of the physiological conditions. However, due to the fact that the corresponding measuring devices, namely the interferometers, had a considerable size, this was hitherto practically impracticable.
Der Erfindung liegt daher die Aufgabe zugrunde, ein Verfahren anzugeben, mit dem eine räumliche Vermessung einer Mehrzahl von biologischen Gewebestrukturen in einem Organ mit Hilfe der Interferometrie kontinuierlich und über einen längeren Zeitraum mittels mobiler Geräte durchgeführt werden kann. Erfindungsgemäß ist daher das Verfahren der eingangs genannten Art dadurch gekennzeichnet, dass bei bekannter räumlicher Erstreckung einer ersten Gewebestruktur des Organs sowohl die Referenzsonde als auch die zumindest eine Messsonde auf das Organ gerichtet wird, wobei der Wegunterschied zwischen den beiden Sonden konstant gehalten wird. Beim erfindungsgemäßen Verfahren wird daher vor der eigentlichen Vermessung eine erste Gewebestruktur des Organs hinsichtlich ihrer räumlichen Erstre- ckung vermessen und bestimmt. Hierfür eignet sich beispielswei- se die Dicke der Cornea, die auch bei schwankendem Augeninnendruck praktisch konstant bleibt. Dadurch, dass nun erfindungsgemäß eine Gewebestruktur am zu vermessenden Organ selbst bereits bekannt ist und als konstant angenommen werden kann, ist es nicht mehr nötig, die zumindest eine Messsonde in einem kon- stanten Abstand zum Organ, also den Gewebestrukturen zu halten, wenn gleichzeitig, wie es der vorliegenden Erfindung entspricht, sowohl die Referenzsonde als auch die Messsonde auf das Organ gerichtet werden und der Wegunterschied zwischen den beiden Sonden konstant gehalten wird. Der Wegunterschied zwi- sehen den beiden Sonden bzw. Lichtleitern ist hierbei stets als Abstand in axialer Richtung, d.h. in Richtung des Wegs des Lichts bzw. des elektromagnetischen Referenz- und Messsignals gemeint. Beim erfindungsgemäßen Verfahren dient somit eine der zu vermessenden biologischen Gewebestrukturen selbst quasi als Referenzreflektor, sodass eine komplexe Anordnung von Linsen und halb durchlässigen Spiegeln im Interferometer nicht mehr notwendig ist. Auch ein variierender Abstand zwischen den beiden Sonden und den zu vermessenden Gewebestrukturen behindert eine präzise Messung der jeweiligen räumlichen Erstreckungen nicht, sodass keine apparativen Vorkehrungen getroffen werden müssen, um das Auge in einem entsprechenden Abstand zu halten. Somit kann mit dem erfindungsgemäßen Vermessungsverfahren der apparative Aufwand eines Interferometers erheblich reduziert werden, sodass neben den Referenz- und Messsonden lediglich eine Recheneinheit mit einer entsprechenden Programmlogik notwendig ist, um die Messdaten verarbeiten und speichern zu können. Gemäß einer bevorzugten Ausführungsform der vorliegenden Erfindung ist das Verfahren dahingehend weitergebildet, dass der Wegunterschied zwischen der Referenzsonde und der zumindest einen Messsonde zum zu vermessenden Organ derart eingestellt und fixiert wird, dass die der ersten Gewebestruktur entsprechenden Interferenzbanden in einer Kopplungskurve die bekannte räumliche Erstreckung dieser Struktur angeben, wobei bevorzugt im Interferogramm den weiteren zu vermessenden Gewebestrukturen Interferenzbanden zugeordnet und die tatsächlichen Abstände der weiteren Gewebestrukturen relativ zum Abstand der der ersten Gewebestruktur entsprechenden Interferenzbanden bestimmt werden. Unter einer Kopplungskurve wird in der Technik der Faseroptik jenes Signal einer Photodiode verstanden, in welchem sich die Interferenz-Muster im AC-Anteil des Signals widerspiegeln. Dieses Signal erhält man durch die Variation der optischen Wellenlänge in einem mittels faseroptischer Komponenten realisierten Michelson Interferometers (Fibre Optics Essentials; K. THY- AGARAJAN, AJOY GHATAK) . Auf diese Weise können die Abstände der jeweiligen biologischen Gewebestrukturen zueinander direkt be- stimmt und aufgezeichnet werden, um in der Folge zur Diagnose herangezogen zu werden. Die erhaltenen Interferogramme können hierbei Interferenzbanden für unterschiedliche Gewebestrukturen aufweisen. Insbesondere wurden mit dem erfindungsgemäßen Verfahren beispielsweise die mittlere Corneadicke (central Cornea thickness, CCT), die Tiefe der vorderen Augenkammer (anterior Chamber depth, ACD) und die Länge des Augapfels (axial length, AL) gemessen. All diese Werte können mit dem Augeninnendruck in Korrelation gesetzt werden und somit bei der ärztlichen Diagnose Berücksichtigung finden. The invention is therefore based on the object of specifying a method with which a spatial measurement of a plurality of biological tissue structures in an organ by means of interferometry can be carried out continuously and over a longer period by means of mobile devices. According to the invention, therefore, the method of the type mentioned above is characterized in that, when the spatial extent of a first tissue structure of the organ is known, both the reference probe and the at least one measuring probe are directed onto the organ, the path difference between the two both probes is kept constant. In the method according to the invention, a first tissue structure of the organ is therefore measured and determined with respect to its spatial extent before the actual measurement. For example, the thickness of the cornea, which remains practically constant even with fluctuating intraocular pressure, is suitable for this purpose. By virtue of the fact that, according to the invention, a tissue structure on the organ to be measured itself is already known and can be assumed to be constant, it is no longer necessary to keep the at least one measuring probe at a constant distance from the organ, ie the tissue structures, if at the same time according to the present invention, both the reference probe and the probe are directed to the organ and the path difference between the two probes is kept constant. The path difference between see the two probes or optical fibers is always meant as a distance in the axial direction, ie in the direction of the path of the light or the electromagnetic reference and measurement signal. In the method according to the invention thus one of the biological tissue structures to be measured itself serves as a quasi reference reflector, so that a complex arrangement of lenses and semi-transparent mirrors in the interferometer is no longer necessary. Even a varying distance between the two probes and the tissue structures to be measured does not hinder a precise measurement of the respective spatial extent, so that no apparatus precautions must be taken to keep the eye at a suitable distance. Thus, with the surveying method according to the invention, the expenditure on equipment of an interferometer can be considerably reduced so that apart from the reference and measuring probes, only one arithmetic unit with a corresponding program logic is necessary in order to be able to process and store the measured data. According to a preferred embodiment of the present invention, the method is developed such that the path difference between the reference probe and the at least one measuring probe is adjusted and fixed to the organ to be measured such that the interference bands corresponding to the first tissue structure in a coupling curve, the known spatial extent of this structure specify, preferably in the interferogram associated with the other tissue structures to be measured interference bands and the actual distances of the other tissue structures are determined relative to the distance of the first tissue structure corresponding interference bands. A coupling curve is understood in the art of fiber optics that signal of a photodiode, in which the interference patterns are reflected in the AC component of the signal. This signal is obtained by varying the optical wavelength in a fiberoptic component Michelson interferometer (Fiber Optics Essentials, K. THYAGARAJAN, AJOY GHAKAK). In this way, the distances of the respective biological tissue structures from each other can be directly determined and recorded in order to subsequently be used for diagnosis. The interferograms obtained can have interference bands for different tissue structures. In particular, the method according to the invention has been used to measure, for example, the mean corneal thickness (CCT), the anterior chamber depth (ACD) and the length of the eyeball (axial length, AL). All of these values can be correlated with intraocular pressure and thus taken into account in the medical diagnosis.
Die Interferenzbanden haben die Grundform einer Gaußschen Glockenkurve und weisen abhängig von der Kohärenzlänge des eingesetzten Lichts eine gewisse Breite auf, die als "dynamic ränge" bezeichnet wird. Die Erfindung ist daher bevorzugt dahingehend weitergebildet, dass die genauen Positionen der Interferenzbanden durch Abstandsbestimmung der Maxima der Gaußschen Hüllkurven der Interferenzbanden bestimmt werden. Bevorzugt werden die über einen bestimmten Zeitraum ermittelten Messdaten zur Berechnung der relativen Bewegungen der Mehrzahl von Gewebestrukturen des Organs zueinander herangezogen. Der behandelnde Arzt kann auf diese Weise den Verlauf des Augeninnendrucks über den betreffenden Zeitraum ermitteln und entspre- chende Informationen für die indizierte Behandlung erhalten. The interference bands have the basic shape of a Gaussian bell curve and have a certain width, referred to as the "dynamic rank", depending on the coherence length of the light used. The invention is therefore preferred further developed that the exact positions of the interference bands are determined by distance determination of the maxima of the Gaussian envelopes of the interference bands. Preferably, the measured data determined over a certain period of time are used to calculate the relative movements of the plurality of tissue structures of the organ relative to one another. The treating physician can then determine the course of intraocular pressure over the period in question and receive appropriate information for the indicated treatment.
Bei Verwendung von lediglich zwei Sonden bzw. Lichtleitern, dem Referenzlichtleiter und dem Messlichtleiter können lediglich eindimensionale Längeninformationen gewonnen werden. Um jedoch ein dreidimensionales Bild von dem untersuchten Organ zu erhalten, ist die Erfindung mit Vorteil dahingehend weitergebildet, dass mehrere in Form eines Array angeordnete Messsonden eingesetzt werden und von einem elektronischen Schaltkreis nacheinander zur Ermittlung von Messdaten aktiviert werden. Aufgrund der extrem kurzen Zeit, die für eine räumliche Vermessung bzw. Längenbestimmung nötig ist, kann bei entsprechender Beschaltung der auf dem Array nebeneinander angeordneten Lichtleiter bzw. Sonden eine Vielzahl von Messungen in sehr kurzer Zeit vorgenommen werden, sodass praktisch eine Momentaufnahme des betref- fenden Organs im Sinne einer räumlichen, dreidimensionalen Vermessung zu einem gegebenen Zeitpunkt erstellt werden kann. When using only two probes or light guides, the reference light guide and the measuring light guide only one-dimensional length information can be obtained. However, in order to obtain a three-dimensional image of the examined organ, the invention is developed to advantage in that a plurality of arranged in the form of an array probes are used and activated by an electronic circuit sequentially for the determination of measurement data. Due to the extremely short time required for a spatial measurement or length determination, a corresponding number of measurements can be made in a very short time, with appropriate wiring of the light guides or probes arranged next to each other on the array, so that practically a snapshot of the relevant Organ in the sense of a spatial, three-dimensional survey at a given time can be created.
Die Vorrichtung zur Durchführung des erfindungsgemäßen Verfahrens ist dadurch gekennzeichnet, dass Referenz- und Messsonden eines Interferometers an einer von einem Patienten tragbaren Halterung festgelegt sind und mit einer tragbaren Recheneinheit verbunden sind. Der Patient trägt somit die Recheneinheit und die Halterung mit sich, wobei die Halterung beispielsweise in Form einer Brille ausgebildet sein kann. Bevorzugt weist die Halterung Mittel zum Einstellen und Fixieren des Wegunterschieds zwischen der Referenzsonde und der zumindest einen Messsonde zum zu vermessenden Organ auf. The device for carrying out the method according to the invention is characterized in that reference and measuring probes of an interferometer are fixed to a holder that is portable by a patient and are connected to a portable computing unit. The patient thus carries the arithmetic unit and the holder with him, wherein the holder may be formed, for example in the form of glasses. The holder preferably has means for setting and fixing the path difference between the reference probe and the at least one measuring probe to the organ to be measured.
Die Erfindung wird nachfolgend anhand eines in Zeichnung dargestellten Ausführungsbeispiels näher erläutert. In dieser zeigen Figur 1 die prinzipielle Anordnung der Referenz- und Messsonden, Figur 2 eine Kopplungskurve wie sie bei dem erfindungsge- mäßen Verfahren erhalten wird, Figur 3 eine Kurve, die die Änderungen eines Messwerts über die Zeit anzeigt und Figur 4 eine Darstellung eines Anwendungsbeispiels der Erfindung. The invention will be explained in more detail with reference to an embodiment shown in the drawing. 1 shows the basic arrangement of the reference and measuring probes, FIG. 2 shows a coupling curve as obtained in the method according to the invention, FIG. 3 shows a curve indicating the changes of a measured value over time, and FIG. 4 shows a representation of an application example the invention.
In Fig. 1 ist mit 1 ein Auge als zu vermessendes Organ bezeich- net, wobei die vordere Augenkammer 4 von der Linse 2 und der Cornea 3 begrenzt wird. Die räumliche Erstreckung 5 der vorderen Augenkammer 4, d.h. der Abstand zwischen der Linse 2 und der Cornea 3 unterliegt bei wechselndem Augeninnendruck messbaren Schwankungen und kann somit zur Bestimmung des Augeninnen- drucks herangezogen werden, welcher ein wichtiges diagnostisches Indiz im Zusammenhang mit Glaukom ist. In FIG. 1, 1 denotes an eye as an organ to be measured, the anterior chamber 4 being delimited by the lens 2 and the cornea 3. The spatial extent 5 of the anterior chamber 4, i. The distance between the lens 2 and the cornea 3 is subject to measurable fluctuations with changing intraocular pressure and can thus be used to determine the intraocular pressure, which is an important diagnostic indicator in connection with glaucoma.
Zur Messung der räumlichen Erstreckungen der relevanten Gewebestrukturen werden nun gemäß der vorliegenden Erfindung zwei Lichtleiter 6 und 7 mit einem einstell- und fixierbaren Wegunterschied ÄL in einem Abstand D zum zu untersuchenden Organ an einer nicht näher dargestellten Halterung 8 festgelegt. Mit 9 ist ein nicht näher bezeichneter Lichtleiter bezeichnet, der das reflektierte Licht aus den Lichtleitern 6 und 7 zu einer ebenfalls nicht dargestellten Recheneinheit leitet. In order to measure the spatial extent of the relevant tissue structures, according to the present invention, two light guides 6 and 7 are now fixed to a holder 8 (not shown) at a distance D to the organ to be examined which is adjustable and fixable. 9 with an unspecified light guide is referred to, which directs the reflected light from the optical fibers 6 and 7 to a computing unit, also not shown.
In Fig. 2 ist zu erkennen, dass sich in Abhängigkeit von den Abständen unterschiedlicher Strukturen in einem Augenmodell 10, welches von einer Glasplatte 11 und einem Spiegel 12 gebildet ist, in einer Kopplungskurve 13 Interferenzbanden 14 ergeben, wobei bei geeigneter Einstellung von ÄL der Abstand X zwischen der dritten und der vierten Bande unabhängig vom Abstand D der mittleren Dicke der Cornea 3 bzw. der die Cornea repräsentie- renden Glasplatte 11 entspricht. Der Abstand Y zwischen der vierten und der sechsten Interferenzbande entspricht der räumlichen Erstreckung 5 der vorderen Augenkammer 4. Sind weitere Strukturen vorhanden, die Licht reflektieren, wie z.B. eine nicht dargestellte Retina in einem Auge, so würden weitere In- terferenzbanden abgebildet, die den Abstand der Retina zu den anderen Strukturen angeben. In FIG. 2 it can be seen that, depending on the distances of different structures in an eye model 10, which is formed by a glass plate 11 and a mirror 12 is in a coupling curve 13 interference bands 14 result, with a suitable setting of ÄL the distance X between the third and the fourth band regardless of the distance D corresponds to the average thickness of the cornea 3 and the Cornea representing glass plate 11. The distance Y between the fourth and the sixth interference band corresponds to the spatial extent 5 of the anterior chamber 4. If there are other structures which reflect light, such as a retina (not shown) in an eye, then further interference bands would be displayed which represent the distance specify the retina to the other structures.
Fig. 3 zeigt nun einen Graphen der Werte für die räumliche Erstreckung 5 der vorderen Augenkammer 4 und es ist zu erkennen, dass diese über die Zeit Fluktuationen unterworfen ist. FIG. 3 now shows a graph of the values for the spatial extent 5 of the anterior chamber 4 and it can be seen that it is subject to fluctuations over time.
In Fig. 4 ist zu erkennen, dass das Verfahren gemäß der vorliegenden Erfindung bei einem Interferometer angewendet werden kann, bei welchem eine Halterung 8 die Lichtleiter 6 und 7 trägt, wobei die Lichtleiter 6 und 7 einer Recheneinheit 15 zugeführt sind, in der die Auswertung der Interferenzmuster erfolgt. Es wurde somit eine tragbare Messvorrichtung geschaffen, die eine kontinuierliche Vermessung der räumlichen Erstreckung von biologischen Gewebestrukturen ermöglicht. In Fig. 4 it can be seen that the method according to the present invention can be applied to an interferometer in which a holder 8 carries the optical fibers 6 and 7, wherein the optical fibers 6 and 7 are fed to a computing unit 15 in which the evaluation the interference pattern takes place. Thus, a portable measuring device has been provided which allows continuous measurement of the spatial extent of biological tissue structures.

Claims

Patentansprüche : Claims:
1. Verfahren zum räumlichen Vermessen einer Mehrzahl von hintereinander liegenden biologischen Gewebestrukturen in einem Organ, insbesondere in einem Auge, durch Auswertung von Inter- ferogrammen erhalten aus reflektiertem, niedrig-kohärentem Licht aus einer auf einen Referenzreflektor gerichteten Referenzsonde und zumindest einer Messsonde, dadurch gekennzeichnet, dass bei bekannter räumlicher Erstreckung einer ersten Gewebestruktur des Organs sowohl die Referenzsonde als auch die zumindest eine Messsonde auf das Organ gerichtet wird, wobei der Wegunterschied zwischen den beiden Sonden konstant gehalten wird. 1. A method for spatially measuring a plurality of successive biological tissue structures in an organ, in particular in an eye, by evaluating interferograms obtained from reflected, low-coherent light from a reference probe directed to a reference probe and at least one probe, characterized in that, given a known spatial extent of a first tissue structure of the organ, both the reference probe and the at least one measuring probe are directed onto the organ, the path difference between the two probes being kept constant.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass der Wegunterschied zwischen der Referenzsonde und der zumindest einen Messsonde zum zu vermessenden Organ derart eingestellt und fixiert wird, dass die der ersten Gewebestruktur entsprechenden Interferenzbanden in einer Kopplungskurve die bekannte räumliche Erstreckung dieser Struktur angeben. 2. Method according to claim 1, characterized in that the path difference between the reference probe and the at least one measuring probe is adjusted and fixed in such a way that the interference bands corresponding to the first tissue structure indicate the known spatial extent of this structure in a coupling curve.
3. Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass im Interferogramm den weiteren zu vermessenden Gewebestrukturen Interferenzbanden zugeordnet und die tatsächlichen Abstände der weiteren Gewebestrukturen relativ zum Abstand der der ersten Gewebestruktur entsprechenden Interferenzbanden bestimmt werden. 3. The method according to claim 1 or 2, characterized in that in the interferogram associated with the other tissue structures to be measured interference bands and the actual distances of the other tissue structures are determined relative to the distance of the first tissue structure corresponding interference bands.
4. Verfahren nach Anspruch 1, 2 oder 3, dadurch gekennzeich- net, dass die genauen Positionen der Interferenzbanden durch4. The method of claim 1, 2 or 3, marked thereby, that the exact positions of the interference bands by
Abstandsbestimmung der Maxima der Gaußschen Hüllkurven der Interferenzbanden bestimmt werden. Distance determination of the maxima of the Gaussian envelopes of the interference bands are determined.
5. Verfahren nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass die über einen bestimmten Zeitraum ermittelten Messdaten zur Berechnung der relativen Bewegungen der Mehrzahl von Gewebestrukturen des Organs zueinander herangezogen werden. 5. The method according to any one of claims 1 to 4, characterized in that the determined over a certain period measurement data for calculating the relative movements of the plurality of tissue structures of the organ are used to each other.
6. Verfahren nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass mehrere in Form eines Array angeordnete Messsonden eingesetzt werden und von einem elektronischen Schaltkreis nacheinander zur Ermittlung von Messdaten aktiviert werden. 6. The method according to any one of claims 1 to 5, characterized in that a plurality of arranged in the form of an array probes are used and activated by an electronic circuit sequentially for the determination of measurement data.
7. Vorrichtung zum räumlichen Vermessen einer Mehrzahl von hintereinander liegenden biologischen Gewebestrukturen in einem Organ, insbesondere in einem Auge, nach einem der Ansprüche 1 bis 6, umfassend ein Interferometer mit einer Referenzsonde und einer Messsonde, die so an einer von einem Patienten tragbaren Halterung festgelegt sind, dass sowohl die Referenzsonde als auch die Messsonde auf das Organ gerichtet sind, und weiters mit einer tragbaren Recheneinheit verbunden sind. 7. An apparatus for spatially surveying a plurality of successive biological tissue structures in an organ, in particular in an eye, according to one of claims 1 to 6, comprising an interferometer with a reference probe and a measuring probe, thus fixed to a portable support by a patient are that both the reference probe and the probe are directed to the organ, and further connected to a portable computing unit.
8. Vorrichtung nach Anspruch 7, dadurch gekennzeichnet, dass die Halterung Mittel zum Einstellen und Fixieren des Wegunterschieds zwischen der Referenzsonde und der zumindest einen Messsonde zum zu vermessenden Organ aufweist 8. The device according to claim 7, characterized in that the holder comprises means for adjusting and fixing the path difference between the reference probe and the at least one measuring probe to be measured organ
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