WO2003011135A1 - Anterior chamber diameter measurement system from limbal ring measurements - Google Patents

Anterior chamber diameter measurement system from limbal ring measurements Download PDF

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Publication number
WO2003011135A1
WO2003011135A1 PCT/US2002/023685 US0223685W WO03011135A1 WO 2003011135 A1 WO2003011135 A1 WO 2003011135A1 US 0223685 W US0223685 W US 0223685W WO 03011135 A1 WO03011135 A1 WO 03011135A1
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WO
WIPO (PCT)
Prior art keywords
limbus
eye
diameter
image
illuminated
Prior art date
Application number
PCT/US2002/023685
Other languages
French (fr)
Inventor
Gregg D. Niven
Timothy N. Turner
Original Assignee
Bausch & Lomb Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bausch & Lomb Incorporated filed Critical Bausch & Lomb Incorporated
Priority to AT02756660T priority Critical patent/ATE305750T1/en
Priority to JP2003516373A priority patent/JP2004536653A/en
Priority to CA002454833A priority patent/CA2454833C/en
Priority to EP02756660A priority patent/EP1411831B1/en
Priority to DE60206510T priority patent/DE60206510T2/en
Publication of WO2003011135A1 publication Critical patent/WO2003011135A1/en

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Classifications

    • 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
    • A61B3/117Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for examining the anterior chamber or the anterior chamber angle, e.g. gonioscopes
    • 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

Definitions

  • the present invention relates to a system for measuring the limbus-to-limbus
  • the eye for measurement of the limbal diameter and deriving an anterior chamber diameter from the limbal diameter.
  • LASIK laser assisted in-situ keratomileusis
  • an inter-corneal lens is to measure the diameter of the cornea
  • the limbus is a junction of the cornea of the
  • This limbal diameter measurement is used to determine the diameter of the external boundary of
  • Fig. 1 is a block diagram of a system in accordance with the present
  • Fig. 2 is a flow diagram of a portion of the preferred system in accordance with the present invention
  • Fig 3 is a block diagram of an alternate embodiment of a system in accordance with the present invention.
  • a system for measuring a diameter of a limbus of an eye and for determining iris-angle diameters is described below.
  • the limbal-ring usually occurs must clearly when the illumination directly impinges the limbal region.
  • the limbal-ring can also be seen, but with far less clarity, by indirectly
  • illuminating the limbus via iris scatter or corneal fiber optic conduction illuminating the limbus via iris scatter or corneal fiber optic conduction.
  • This limbal-fiber-ring acts to maintain
  • the ring should be sized to accurately determine the diameter of the limbal-ring.
  • limbal-ring illumination is preferably
  • Fig. 1 shows a system 10, in accordance with the present invention, for
  • System 10 includes an image
  • An output device 19; focusing lens 20, a reflecting mirror 22, and an optional fixation target 24 are also preferably included in system 10. It will be
  • system 10 could be incorporated into a comprehensive eye measurement system, such as the ORBSCANTM system sold by Bausch & Lomb or
  • the optional fixation target 24 includes a fixation light source 26, a pin hole aperture 28, and a beam splitter 30 all cooperating to illuminate a small dot of light
  • illumination source 16 directs a light beam at a first known location relative to the image recorder 14 for illuminating the limbus 34 along line
  • Line 36 represents the light from illumination source 16 that has been reflected by a mirror 22.
  • the illuminated limbal ring 34 then is recorded by image recorder
  • Computer 18 uses image analysis locates the illuminated limbal position in 3- dimensional space
  • the limbal diameter is then calculated from the image of the illuminated ring based
  • the limbal diameters are preferably
  • Illumination source 16 may provide visible or infrared illumination or the
  • preferred red laser light may be used.
  • the preferred embodiment of illumination may be used.
  • source 16 uses an infrared diode laser light collimated into narrow cylindrical beam
  • any illumination source 16 may be used that provides adequate
  • the image recorder preferably a video camera such as a CCD camera 14 is
  • the fixed angle of the illumination source 16 from the image recorder 14 is preferably
  • a first method is where the
  • system 10 has a single fixed beam (represented by line 36), as shown in Fig. 1, and
  • the single fixed beam is manually repositioned a number of times (at least two) in
  • a second embodiment includes two or more fixed beams, such as shown
  • a third embodiment is where a single illumination source is constructed such that the
  • computer 18 may be a stand alone
  • Computer 18 preferably includes a frame
  • Computer 18 preferably further includes an iris-angle calculator 42 and an ICL calculator 44
  • Fig. 2 discloses a flow chart 44 representing software that sets forth the preferred iris-angle calculator 42 and ICL calculator 44 for a patient's eye. This allows a physician to accurately fit an ICL for a patient and thereby achieve optimal
  • Step 48 of Fig. 2 causes camera 14 and digitizer 38 to acquire multiple images, in a rapid fashion, of the illuminated limbal area. It is preferred that the
  • Step 50 then causes computer 18 to analyze the image scene. This analysis
  • illumination ring the fixation target, and a pupil boundary.
  • the location of these portions of each image are preferably done to the nearest pixel accuracy. This will allow a limbal diameter to be measured to accuracy within 0.1 mm.
  • portion of Step 50 includes precisely detecting, preferably to sub-pixel accuracy, the
  • the detected direct slit image is
  • the edge is defined as a mid-threshold
  • Step 52 determines the limbal figure, which is defined as the annular
  • the best limbal plane is determined by known techniques. Imaging and measurements are then preferably registered to a common coordinate system to
  • Step 50 the limbal edges are projected onto the best limbal plane.
  • the different limbal edges are integrated from the different images that have been derived from Step 48 and Step 50.
  • Step 54 determines the iris-angle diameter and includes iris-angle
  • this iris-angle diameter is calculated by interpolating the
  • Direct anatomical measurements can be derived from geometrically accurate B-scans of the anterior segment, using ultrasound or optical
  • B-scans are 2-D sections
  • A-scans give scattering amplitude versus depth via echo time (UBM) or interference path length (OCT).
  • UBM echo time
  • OCT interference path length
  • optical occurring a media interfaces.
  • Step 56 determines an ICL size and includes ICL calculator 44.
  • ICL calculator 44 Preferably,
  • the ICL size is calculated based on the determined iris-angle diameter.
  • the ICL size is then presented to a user on the display 19 connected to system 10.
  • Fig. 3 discloses an alternate embodiment in accordance with the present invention. Specifically, Fig. 3 discloses a system similar to that disclosed above
  • Fig. 3 includes an additional
  • Fig. 3 shows the use of a light filter 60
  • system 10 may be used, as well as various image recorders.
  • various illumination sources may be used, as well as various image recorders.
  • system 10 may be used, as well as various image recorders.

Abstract

A system (10) for measuring a diameter of a limbus of an eye (12). An image recorder (14) is at a known location apart from eye and records an illuminated limbus image. An illumination source (16) at a known location relative to the image recorder (14) illuminates the limbus. A computer device (18) connected to the image recorder (14) determines the diameter of the limbus from the recorded illuminated limbus image.

Description

ANTERIOR CHAMBER DIAMETER MEASUREMENT SYSTEM FROM LIMBAL RING MEASUREMENTS
Background of the Invention
I. Field of the Invention
The present invention relates to a system for measuring the limbus-to-limbus
diameter of an eye and more specifically, to a system using laser-slit illumination of
the eye for measurement of the limbal diameter and deriving an anterior chamber diameter from the limbal diameter.
II. Description of the Related Art
A common measurement for an eye care professional in fitting lenses or
performing surgical procedures such as laser assisted in-situ keratomileusis (LASIK
or for inserting an inter-corneal lens (ICL) is to measure the diameter of the cornea
or the limbus-to-limbus measurement. The limbus is a junction of the cornea of the
eye and the sclera which extends all around the periphery of the cornea. This limbal diameter measurement is used to determine the diameter of the external boundary of
the cornea and is used with LASIK surgery or contact lens fitting. This limbal diameter measurement is also used to determine the internal interior chamber
diameter or angle-to-angle measurement which is critical for properly fitting an ICL
in a patient's eye. It is known to obtain the limbal diameter measurement using what is commonly known as a Holliday disk, or a scale held near the patient's eye, or a
caliper held near the patient's eye. None of these known techniques provide for a precise measurement of the limbal diameter.
If the calculated limbal diameter is sufficiently larger than the actual limbal
diameter, it is possible that an ICL that is too large may be incorrectly inserted into
the patient's eye; thereby causing pressure to the trabecular meshwork and Schlemm's canal. These problems could have an adverse effect on the natural
aqueous flow from the eye or on the refractive outcome following ICL implantation.
Conversely, a calculated limbal diameter that is too small could result in a lens that is too small for the patient's eye. This could be problematic because the ICL could move out of place. Therefore it is important that an easy and accurate system to
measure limbal diameter be obtained.
Brief Description of the Drawings
Fig. 1 is a block diagram of a system in accordance with the present
invention being used on a patient's eye;
Fig. 2 is a flow diagram of a portion of the preferred system in accordance with the present invention; and Fig 3 is a block diagram of an alternate embodiment of a system in accordance with the present invention.
Detailed Description of the Preferred Embodiments
A system for measuring a diameter of a limbus of an eye and for determining iris-angle diameters is described below.
When a beam of light is directed on or near the annular limbal region
connecting the cornea to the sclera in addition to local scatter, a continuous ring of
light emanating from the limbus can be seen. This so called limbal-ring appears for
both visible and infrared illumination and for both monochromatic (e.g., laser or LED) and continuous spectra (e.g., white-light slit-beam). The illuminated limbal-
ring usually occurs must clearly when the illumination directly impinges the limbal region. The limbal-ring can also be seen, but with far less clarity, by indirectly
illuminating the limbus via iris scatter or corneal fiber optic conduction.
It is believed that when light impinges any part of the limbus, the light enters
a circumferential ring of stromal collagen fibers. These collagen fibers act as a light-
pipe and operate to direct the impinging light around the entire circumference of the limbal region. The annular emanation of light thus marks an anatomical ring of collagen fibers. These collagen fibers are directly associated with the limbus and iris angle. This limbal-fiber-ring, buried within the fibrous tunic of the eye, was
previously discovered with x-ray diffraction. This limbal-fiber-ring acts to maintain
the shape of the internally pressurized eye at the limbal joint connecting the cornea
to the sclera.
To accurately determine the diameter of the limbal-ring, the ring should
preferably be clearly illuminated using the above-described light-piping effect. It is
preferred that extraneous surface scatter and indirect illumination via the cornea, iris, or anterior chamber be minimized. Therefore, limbal-ring illumination is preferably
accomplished using a narrow beam directly impinging the limbus.
Fig. 1 shows a system 10, in accordance with the present invention, for
measuring a diameter of a limbus of an eye 12. System 10 includes an image
recorder 14 to be placed at a known location apart from the eye 12 for recording an
illuminated limbus image, at least a first illumination source 16, and a computing
device 18. An output device 19; focusing lens 20, a reflecting mirror 22, and an optional fixation target 24 are also preferably included in system 10. It will be
appreciated that system 10 could be incorporated into a comprehensive eye measurement system, such as the ORBSCAN™ system sold by Bausch & Lomb or
system 10 can be a hand-held stand alone system as shown in Fig. 1. The optional fixation target 24 includes a fixation light source 26, a pin hole aperture 28, and a beam splitter 30 all cooperating to illuminate a small dot of light
along line 32 so as to facilitate fixation of the eye 12 along line 32, which
corresponds to the viewing axis of camera 14.
In operation illumination source 16 directs a light beam at a first known location relative to the image recorder 14 for illuminating the limbus 34 along line
36. Line 36 represents the light from illumination source 16 that has been reflected by a mirror 22. The illuminated limbal ring 34 then is recorded by image recorder
14 which is preferably a charge couple device (CCD) video camera. Computer 18, using image analysis locates the illuminated limbal position in 3- dimensional space
by triangulating the beam in the surface scattered light recorded by the camera 14.
The limbal diameter is then calculated from the image of the illuminated ring based
on the known distance to the eye. Accurate limbal diameters cannot be determined
in the region of the directly impinging light because the directly impinging light
from source 16 overwhelms the camera 14 at the region of the eye immediately adjacent of the impinging light. Therefore, the limbal diameters are preferably
pieced together from at least two different images. As one skilled in the art will appreciate, the registration of the different images by computer 18 is facilitated using
known techniques such as iris texture and pupil edge cues. Illumination source 16 may provide visible or infrared illumination or the
preferred red laser light may be used. The preferred embodiment of illumination
source 16 uses an infrared diode laser light collimated into narrow cylindrical beam
or short-slit. This provides an economical unobtrusive illumination source and gives
superior contrast to the iris and pupil images. As those skilled in the art will appreciate, any illumination source 16 may be used that provides adequate
illumination of the limbal region in order for the camera 14 and computer 18 to
record and detect the limbal region.
The image recorder, preferably a video camera such as a CCD camera 14 is
focused on the limbal plane defined by line 32 and has a narrow beam of light at a
fixed angle from the camera that illuminates the limbus at multiple locations. The fixed angle of the illumination source 16 from the image recorder 14 is preferably
from about 25° to about 90°. The multiple illuminations are preferably implemented in sequence and can be achieved in a number of ways. A first method is where the
system 10 has a single fixed beam (represented by line 36), as shown in Fig. 1, and
the single fixed beam is manually repositioned a number of times (at least two) in
order for the camera 14 to obtain a sufficient number of images to define the limbal diameter. A second embodiment includes two or more fixed beams, such as shown
and described below in connection with Fig. 3, taking images in rapid succession. A third embodiment is where a single illumination source is constructed such that the
beam impinging upon the patient's eye is rotated and scanned around the limbus and
images are recorded by the camera 14 during this scanning procedure.
As those skilled in the art will appreciate, computer 18 may be a stand alone
computer, such as a personal computer or it could be built into a unified instrument as is preferred and shown in Fig. 1. Computer 18 preferably includes a frame
grabber 38 or other device for digitizing images from camera 14. Computer 18 preferably further includes an iris-angle calculator 42 and an ICL calculator 44
described move fully below.
After a sufficient number of illuminated limbal images are recorded by camera 14 and digitized in a memory 40 of computer 18, the computer then
processes the images, as described in relation to Fig. 2 below.
Fig. 2 discloses a flow chart 44 representing software that sets forth the preferred iris-angle calculator 42 and ICL calculator 44 for a patient's eye. This allows a physician to accurately fit an ICL for a patient and thereby achieve optimal
results for the patient. Step 48 of Fig. 2 causes camera 14 and digitizer 38 to acquire multiple images, in a rapid fashion, of the illuminated limbal area. It is preferred that the
images be acquired as rapidly as possible to minimize the effects of system 10 and eye 12 movement, therefore allowing for the most accurate measurements.
Step 50 then causes computer 18 to analyze the image scene. This analysis
includes several steps including the location of the direct slit image, the limbal
illumination ring, the fixation target, and a pupil boundary. The location of these portions of each image are preferably done to the nearest pixel accuracy. This will allow a limbal diameter to be measured to accuracy within 0.1 mm. The next
portion of Step 50 includes precisely detecting, preferably to sub-pixel accuracy, the
edges of the direct slit image by known techniques. The detected direct slit image is
then triangulated into three-dimensional space (3-space) and the outer edges of the
limbal-ring are then precisely detected. Here the edge is defined as a mid-threshold
point near the maximum gradient in back scattered illumination. And finally Step
42 concludes with preferably precisely locating a centroid of the fixation target 24
that is projected onto the eye as described above.
Step 52 then determines the limbal figure, which is defined as the annular
area between the detected edges of Step 50 of the limbal-ring projected onto the best limbal plane. The best limbal plane is determined by known techniques. Imaging and measurements are then preferably registered to a common coordinate system to
eliminate instrument and eye movement between the multiple images. The best
limbal plane in 3-space is then determined from the triangulated slit measurements
of Step 50. Next, the limbal edges are projected onto the best limbal plane. And
finally, the different limbal edges are integrated from the different images that have been derived from Step 48 and Step 50.
Step 54 then determines the iris-angle diameter and includes iris-angle
calculator 42. Preferably, this iris-angle diameter is calculated by interpolating the
iris-angle diameter from the measured limbal ring diameter. The accuracy of the interpolation will increase as anatomical research over different populations is
accomplished to empirically determine the relationship between limbal-ring diameter and the iris-angle diameter. For example, a diameter of a typical limbal
figure will extend from about 10.4 mm to about 13.2 mm. A limbus diameter then
of 11 mm will most likely result in an iris-angle diameter which is about a
millimeter larger or in the particular example 12 mm. This falls within the limbal figure defined by its inner and outer edges. It is believed that the iris-angle diameter
can be accurate to within 0.1 to 0.2 mms where most of the variance comes from
anatomical differences. Direct anatomical measurements can be derived from geometrically accurate B-scans of the anterior segment, using ultrasound or optical
technologies (e.g., ultrasound biomicroscopy (UBM), or optical coherence tomography (OCT), as well as other technologies. B-scans are 2-D sections
constructed from A-scans. A-scans give scattering amplitude versus depth via echo time (UBM) or interference path length (OCT). To generate geometrically accurate
B-scans from the original A-scans, measurement geometry must be taken into
account, in addition to the diagnostic wave speed for translating temporal measurements or path length into A-scan depth, and wave refraction (acoustic or
optical) occurring a media interfaces.
Step 56 determines an ICL size and includes ICL calculator 44. Preferably,
the ICL size is calculated based on the determined iris-angle diameter. The ICL size is then presented to a user on the display 19 connected to system 10.
Fig. 3 discloses an alternate embodiment in accordance with the present invention. Specifically, Fig. 3 discloses a system similar to that disclosed above
with reference to Fig. 1 except that the embodiment of Fig. 3 includes an additional
illumination source 16' and a reflection mirror 22' and also a switching source 58 for sequentially switching the illumination sources 16 and 16' for obtaining the
required multiple limbal images. In addition, Fig. 3 shows the use of a light filter 60
for filtering out unwanted light frequencies thereby providing a recorded limbus having an optimal contrasting image. There has been shown and described a system for measuring the limbal
diameter and it will be appreciated that various modifications and variations of the present invention are possible in light of the descriptions set forth without departing
from the spirit and scope of the invention. For example, various illumination sources may be used, as well as various image recorders. In addition, system 10
could have a fixed focus and therefore, the entire system 10 is moved relative to the eye 12 until a focused limbus illumination is achieved.

Claims

What is Claimed Is:
1. A system for measuring a diameter of a limbus of an eye comprising:
an image recorder at a known location apart from the eye for recording an
illuminated limbus image;
at least a first illumination source at a first known location relative to the image recorder for illuminating the limbus; and
a computing device connected to the image recorder for determining the
diameter of the limbus from the recorded illuminated limbus.
2. The system of claim 1 further including an output device for displaying the
recorded image and diameter of the limbus.
3. The system of claim 1 further including a fixation target associated with the
image recorder and for providing the eye with a reference target thereby preventing unwanted eye movement.
4. The system of claim 1 wherein the image recorder is a video camera.
5. The system of claim 1 further including: a second illumination source at a second known location relative to the image
recorder for illuminating the limbus;
a switching device connected to the first and second illumination sources for sequentially enabling the first and second illumination sources for
allowing the image recorder to record at least one image illuminated
by each of the first and second illumination sources; and
wherein the computing device combines at least one recorded image
illuminated by the first illumination source and at least one recorded
image illuminated by the second illumination source for determining
the diameter of the limbus.
6. The system of claim 1 wherein the illumination source is an infrared source.
7. The system of claim 1 wherein the illumination source is a laser.
8. The system of claim 7 wherein the laser is a slit source.
9. The system of claim 8 wherein the laser is red.
10. The system of claim 1 wherein the computing device further includes an iris-
angle diameter calculator for calculating a diameter of an iris-angle of the eye from the determined limbus diameter.
11. The system of claim 1 wherein the computing device further includes an
intra-corneal lens (ICL) calculator for calculating a proper ICL size for the eye from the determined limbus diameter.
12. The system of claim 1 wherein the system has a fixed focus and therefore the
entire system is moved relative to the eye until a focused limbus illumination
is achieved.
13. The system of claim 1 wherein the image recorder is located along an optical
axis of the eye.
14. The system of claim 1 wherein the image recorder includes a light filter for filtering out unwanted light frequencies thereby providing a recorded limbus
having an optimal contrasting image.
15. The system of claim 1 wherein the computing device determines the limbus
diameter using triangulation.
16. The system of claim 1 wherein the illumination source is placed at an angle from about 25° to about 90° from the image recorder.
17. An eye measurement system comprising:
a camera for recording an illuminated image of a limbus of an eye wherein
the camera is to be placed at a known location from the eye; first and second laser slit lamps at first and second known locations relative
to the camera for illuminating the limbus; a switch connected to the lamps for alternately enabling the first and second
lamps for allowing the camera to record an image of the limbus
illuminated by each of the first and second lamps; and
a computer including a frame grabber connected to the camera and switch for
digitizing the illuminated limbus images and calculating one or more
of a limbus diameter, an iris-angle diameter, and an inter-corneal lens size for the eye being measured.
18. The system of claim 17 further including an output device for displaying the
recorded image and one or more of the calculated limbus diameter, iris-angle
diameter, and the inter-corneal lens size.
19. The system of claim 17 further including a fixation target associated with the camera and for providing the eye with a reference target thereby preventing
unwanted eye movement.
20. The system of claim 17 wherein the system has a fixed focus and therefore
the entire system is moved relative to the eye until a focused limbus
illumination is achieved.
21. The system of claim 17 wherein the image recorder is located along an
optical axis of the eye.
22. The system of claim 17 wherein the image recorder includes a light filter for filtering out unwanted light frequencies thereby providing a recorded limbus
having an optimal contrasting image.
23. The system of claim 17 wherein the system determines the limbus diameter using triangulation.
24. The system of claim 17 wherein the laser slit lamps are placed at an angle
from about 25° to about 90° from the camera.
PCT/US2002/023685 2001-07-30 2002-07-24 Anterior chamber diameter measurement system from limbal ring measurements WO2003011135A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AT02756660T ATE305750T1 (en) 2001-07-30 2002-07-24 SYSTEM FOR CALCULATION OF THE DIAMETER OF THE ANTERIOR CHAMBER FROM MEASUREMENTS OF THE LIMBUS RING
JP2003516373A JP2004536653A (en) 2001-07-30 2002-07-24 Anterior chamber diameter measurement system by measuring limbalring
CA002454833A CA2454833C (en) 2001-07-30 2002-07-24 Anterior chamber diameter measurement system from limbal ring measurements
EP02756660A EP1411831B1 (en) 2001-07-30 2002-07-24 Anterior chamber diameter measurement system from limbal ring measurements
DE60206510T DE60206510T2 (en) 2001-07-30 2002-07-24 SYSTEM FOR CALCULATING THE DIAMETER OF THE FRONT CHAMBER FROM MEASUREMENTS OF THE LIMBUS RING

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/918,678 2001-07-30
US09/918,678 US6830334B2 (en) 2001-07-30 2001-07-30 Anterior chamber diameter measurement system from limbal ring measurement

Publications (1)

Publication Number Publication Date
WO2003011135A1 true WO2003011135A1 (en) 2003-02-13

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US (1) US6830334B2 (en)
EP (1) EP1411831B1 (en)
JP (1) JP2004536653A (en)
CN (1) CN1273074C (en)
AT (1) ATE305750T1 (en)
CA (1) CA2454833C (en)
DE (1) DE60206510T2 (en)
ES (1) ES2250688T3 (en)
WO (1) WO2003011135A1 (en)

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US6830334B2 (en) 2004-12-14
ATE305750T1 (en) 2005-10-15
CA2454833C (en) 2008-12-16
CN1561181A (en) 2005-01-05
DE60206510T2 (en) 2006-05-11
CN1273074C (en) 2006-09-06
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US20030020871A1 (en) 2003-01-30
CA2454833A1 (en) 2003-02-13

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