EP0485450A1 - Appareil de photocoagulation - Google Patents

Appareil de photocoagulation

Info

Publication number
EP0485450A1
EP0485450A1 EP19900911809 EP90911809A EP0485450A1 EP 0485450 A1 EP0485450 A1 EP 0485450A1 EP 19900911809 EP19900911809 EP 19900911809 EP 90911809 A EP90911809 A EP 90911809A EP 0485450 A1 EP0485450 A1 EP 0485450A1
Authority
EP
European Patent Office
Prior art keywords
lens
eye
slit lamp
microscope
patient
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
EP19900911809
Other languages
German (de)
English (en)
Inventor
Anthony Raven
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Keeler Ltd
Original Assignee
Keeler Ltd
Scientific Generics Ltd
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 Keeler Ltd, Scientific Generics Ltd filed Critical Keeler Ltd
Publication of EP0485450A1 publication Critical patent/EP0485450A1/fr
Ceased legal-status Critical Current

Links

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
    • A61B3/13Ophthalmic microscopes
    • A61B3/135Slit-lamp microscopes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F9/00821Methods or devices for eye surgery using laser for coagulation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B2018/2015Miscellaneous features
    • A61B2018/2025Miscellaneous features with a pilot laser
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F2009/00861Methods or devices for eye surgery using laser adapted for treatment at a particular location
    • A61F2009/00863Retina

Definitions

  • This invention relates to photocoagulation apparatus incorporating lasers for ophthalmic use.
  • Laser photocoagulation has become a standard procedure for the treatment of retinal disorders, and numerous types of apparatus have been disclosed for focusing and aiming a beam of laser light onto a desired area of the retina for this purpose.
  • Various forms of such apparatus are disclosed in EP-A-0293126 all of which include an infra-red laser diode source and a dichroic beam splitter arranged to deflect the laser beam into the patient's eye such that a clinician may view the region of the eye being treated through the beam splitter without being exposed to the laser light.
  • One embodiment of the apparatus is in the form of a unit adapted to be attached to an ophthalmic slit lamp, which is a standard piece of medical equipment comprising an illuminating system and a microscope, and is traditionally used for observing the interior of the eye.
  • an ophthalmic slit lamp which is a standard piece of medical equipment comprising an illuminating system and a microscope, and is traditionally used for observing the interior of the eye.
  • the photocoagulating unit may conveniently be mounted such that the beam splitter through which the clinician observes the patient's eye is mounted in a head part of the apparatus disposed between the slit lamp microscope and the patient, the beam splitter deflecting the laser light from a diode source located below the optical path of the microscope into such optical path so that the viewing and treatment beams are substantially aligned between the beam splitter and the patient's eye.
  • a slit- lamp traditionally incorporates a suitable chin and head rest whereby the patient's head is located such that the focal point of the slit-lamp microscope approximately coincides with the retina, fine adjustment in this respect being accommodated by adjusting the position of the microscope relative to the patient.
  • the photocoagulation unit may incorporate an adjustable optical system for focusing the infra-red laser beam to a point coincident with the focal point of the slit-lamp microscope.
  • a head part of the photocoagulation apparatus can, in some circumstances, undesirably restrict the clinician's access to the patient's eye in particular for inserting and using a contact lens orr the eye as is usual in this type of treatment.
  • a negative (i.e. diverging) lens is permanently mounted between the slit lamp microscope and the beam splitter of the known photocoagulation apparatus to move the focal point of the microscope further away from the microscope so as to increase the working distance available.
  • Such a system has been successfully used where the treatment involves a contact lens such as the so-called Goldma -three mirror lens applied to the patient's eye which is designed to cancel the optical power of the eye to allow the laser and viewing beams to be focused directly on the retina.
  • the Goldman lens is also usually used for anterial treatments in which treatment is carried out on parts of the eye in front of the retina e.g. glaucoma treatment.
  • there are other.treatment configurations involving a different form of contact lens such as the so-called Mainster lens adapted to form a real image of the retina in front of the patient's eye, and it is necessary to accommodate such a configuration within the motion limits of the slit-lamp microscope. In such a system there is a need to focus the treatment beam and microscope in front of the patient's eye so that they can be refocused on the retina by the contact lens.
  • the invention provides a photocoagulation apparatus adapted for attachment to an ophthalmic slit lamp, the apparatus comprising at least one laser source arranged to direct treatment laser light to the eye of a patient via a beam splitter mounted in a head part of the apparatus which is adapted to be located between the microscope of a slit lamp and the eye of a patient, whereby in use of the apparatus a clinician may view the eye through the slit lamp microscope via the beam splitter during treatment without exposure to the treatment light, wherein at least one adjustable or detachable lens is arranged between the beam splitter and the eye of the patient for selectively varying together the working distance(s) at which the treatment laser beam and slit lamp microscope are focused in front of the head part of the apparatus.
  • a longer working distance may be selected in treatment configurations wherein the microscope and treatment beam are focused directly onto the retina, whereas the working distance may be reduced to accommodate treatments in which the focal points of the treatment beam and microscope need to coincide with a real image of the retina in front of the eye produced by a contact lens.
  • the adjustable lens arrangement is located in front of the beam splitter of the phtocoagulation apparatus, i.e. between the beam splitter and the patient's eye so that the focal points of the treatment beam and slit lamp microscope are adjusted simultaneously. In this way the clinician may readily change the apparatus from one mode of operation to the other (as and when a contact lens on the patient's eye is changed) without having to refocus the treatment beam.
  • the apparatus preferably comprises a single adjustable or detachable lens movably or detachably mounted by suitable means in front of the beam splitter.
  • the lens is displacable into and out of the optical path on a movable carriage.
  • a single negative i.e.
  • diverging lens may be provided which is located in the optical path when it is desired to increase the working distance as aforesaid, and is moved out of the optical path so that the working distance corresponds to that provided by the slit lamp microscope uncorrected for treatments in which the focal point coincides with a real image of the retina in front of the eye (in such configurations the total working distance available between the patient's eye and the apparatus is in any case increased as compared with the arrangement in which the treatment beam and microscope are focused directly on the retina) .
  • a negative lens of increased focal length may be substituted when the alternative mode of operation is to be used, whereby the working distance is still increased but by a lesser extent.
  • a first negative lens is permanently disposed between the beam splitter and the slit lamp microscope, and is thus effective permanently to increase the distance of the focal point of the microscope in front of the apparatus by a predetermined amount. Adjustment of the working distance may then be achieved by locating either a converging or diverging lens in front of the beam splitter to move the focal points of the microscope and treatment beam towards or away from the apparatus as appropriate.
  • a diverging lens permanently located between the beam splitter and the microscope has a focal length selected to provide a working distance for the microscope suitable for treatments in which a contact lens creates an image of the retina in front of the patient's eye, and a diverging lens is ovably mounted in front of the beam splitter to increase the focal length by a predetermined amount to accommodate the alternative mode of treatment in which the treatment light is focused directly on the retina.
  • Such an arrangement has a practical advantage in that, by appropriately selecting the focal lengths of the two negative lenses, it has been found that a substantially constant variation in the size of the "spot" formed on the retina by the treatment beam can be achieved by a predetermined displacement of the apparatus head out of a position in which the beam is precisely focused to a point on the retina, regardless of whether or not the removable lens is mounted to the apparatus.
  • This is advantageous in that with many treatments of this type it is desirable to carry out the treatment with the treatment beam not precisely focused on the retina so as to produce a predetermined spot size.
  • the spot size of the out of focus beam remains constant for the different modes of treatment without having to reposition the photocoagulation apparatus with respect to the slit lamp each time the working distance is adjusted.
  • a permanent lens with a focal length of substantially -300mm combined with a displaceable one of substantially -83mm have been found advantageous for providing the desired working lengths together with substantially constant spot size variation within working limits.
  • the axis of the or each lens is slightly inclined (by e.g. 5-10°) or is slightly offset with respect to the optical axis of the microscope.
  • a lens located in front of the beam splitter it is preferable that it is offset, since inclining the lens takes up slightly more of the working space in front of the lens.
  • Fig. 1 is a schematic vertical cross section illustrating apparatus in accordance with the invention
  • Figs. 2 to 5 illustrate schematically the beam splitter of the apparatus and the effect, on the working distance by "the inclusion of an adjustable lens system in accordance with the invention
  • Fig. 6 is a front view on an enlarged scale of the head part of the apparatus, illustrating the mounting arrangement for the movable lens.
  • a photocoagulation apparatus 20 is adapted for use as an add-on demountable attachment for a standard slit lamp 30.
  • the slit lamp which may take a number of standard forms, traditionally incorporates a tonometer mount 14 and a microscope 15.
  • An illuminating light source 16 is arranged above the slit lamp mirror 17, whereby, in normal use of the slit lamp, a clinician may view a patient's retina via the microscope 14.
  • the photocoagulation apparatus may be mounted onto the tonometer mount 14 of the slit lamp by suitable means.
  • the photocoagulation apparatus includes one or more high power infra-red laser diodes 1, light from which is collimated by a high numerical aperture lens 2 and is then expanded by an anamorphic prism pair 3 along the long axis of the infra- red laser diode output whereby to reduce the image size on that axis.
  • the beam from a second infra-red laser diode can be combined with that of the illustrated one using a polarising cube as described in EP-A-0293126.
  • a beam of visible laser light for aiming the infra-red beam is produced by a visible laser diode 4 and collimated by a lens 5, the visible beam being combined with the infra ⁇ red beam by a dichroic cube 7.
  • the combined visible a_d infra-red beams are then relayed and expanded by telescope lenses 8, 9 and are focussed to a point substantially confocal with the slit lamp microscope 15 by a lens 10.
  • telescope lenses may be adjusted by the clinician to ensure that the focal points of the infra-red and visible laser light and of the slit lamp microscope are coincident.
  • a wavelength selective mirror 11 acts as the beam splitter adapted to reflect all of the infra-red laser light into the patient's eye 31, but to enable a clinician to view the eye via the microscope 15 and beam splitter 11 without the risk of the clinician's eyes being exposed to the treatment light.
  • aligned windows 32,33 are provided in the upper or head part of the apparatus 20.
  • the windows are provided with suitable means for mounting therein negative (i.e. diverging) lenses.
  • a contact lens such as the so-called Goldman lens is arranged on the patient's eye to cancel out the optical power of the eye so that the treatment and aiming laser beams are focussed directly on the retina.
  • the slit lamp microscope 15 must therefore also be focussed directly on the retina. Accordingly, the working distance between the head part of the apparatus 20 and the patient's eye is restricted by the maximum focal length of the slit lamp microscope.
  • Fig. 2 The restriction of the working distance W between the focal point F of the slit lamp microscope and treatment beam is illustrated schematically in Fig. 2 (in which certain parts of the apparatus have been removed for clarity) .
  • the preferred apparatus is provided with a first negative lens 40 which is permanently located between the slit lamp microscope 15 and the beam splitter 11 in window 33. The effect of this diverging lens is to move the focal point F away from the microscope 15 whereby the working distance W is increased.
  • the telescope lenses are adjusted to refocus the laser light at the new focal point of the microscope.
  • the contact lens As described above, in alternative treatments a different form of contact lens is applied to the patient's eye, such as the Mainster lens, which is adapted to produce a real image of the retina in front of the patient's eye.
  • the slit lamp microscope and treatment and aiming beams need to be focussed at a point in front of the eye, so that they are re-focussed on the retina by the contact lens.
  • the first negative lens 40 has a focal length selected for providing a working distance W suitable for accommodating this form of treatment.
  • a longer working distance W is required, and this is achieved by locating a second negative lens 41 adjacent the window 32 i.e. between the beam splitter 11 and the patient's eye 31. As shown in Fig. 4 this is effective to increase the focal lengths simultaneously both of the microscope 15 and of the treatment and aiming laser beams.
  • the clinician can effectively switch the apparatus from one mode of treatment to the other simply by moving the second diverging lens 41 into and out of the optical path.
  • Figure 6 illustrates the preferred mounting arrangement for the movable lens 41, which comprises a slidable carriage 50 movable upwardly and downwardly on rail members 51 by means of knobs 52 which project outside a casing (not shown) of the apparatus for manual engagement by a clinician.
  • the rail members 51 engage in slots formed in the sides of the carriage 50.
  • the lens 40 is tilted with respect to the optical axis so as to reduce the effect of light being reflected back into the microscope 15.
  • the lens 41 may also be similarly tilted, although, as shown in Fig. 5, it its central axis may instead be slightly offset from the optical axis in the lateral direction. This avoids reducing the working distance by tilting the lens 41.
  • the offsetting of the lens 41 with respect to the optical axis A results in upward displacement of the focal point F, as shown in Figure 5, but this can easily be compensated for by the clinician.
  • adjustable lenses may be provided.
  • the lens 40 may be omitted, and the working distance W shown in Figure 2 used for treatments in which the focal point is at a real image of the patient's retina in front of the eye. In some cases there may be sufficient working distance with such an arrangement for this sort of treatment.
  • a single displaceable negative lens 41 is therefore provided to increase the working distance W when the focal point F needs to be on the retina itself.
  • the power of the permanent lens 40 may be increased to provide a longer working distance similar to that shown in Fig. 4.
  • the movable lens 41 may instead be a converging lens of suitable power adapted suitably to reduce the working distance W to be similar to that shown in Fig. 3.
  • the arrangement of two negative i.e.
  • diverging lenses has a particular practical advantage. As described above, in practice many treatments are carried out with the treatment beam not precisely focussed with respect to the retina. In the preferred embodiment the "spot" size is adjusted by shifting the photocoagulation apparatus back and forth. By selecting a suitable combination of diverging lenses a constant spot size variation for a particular displacement of the apparatus may be achieved regardless of whether the second diverging lens 41 is in the optical path. This cannot be achieved in practice by using a movable negative lens on its own (at least whilst at the same time providing desired working lengths W) .
  • the clinician may adjust the apparatus to provide a predetermined spot size with the treatment.beam directly focussed on the retina, for example, and then when the apparatus is switched to an alternative mode of operation by the movement of the second lens 41 into the optical path, a similar spot size is provides at the plane of the virtual image of the retina defined in front of the patient's eye. There is therefore no need to adjust the position of the apparatus 20 each time the mode of treatment is changed.
  • a combination of focal lengths of -300mm for the lens 40 and -83mm for the lens 41 are convenient for providing the appropriate working distances together with the constant spot size variation within the working range. With such an arrangement the movement of the second lens 41 into the optical path increases the working distance by about 15 mm. Other combinations of focal length are however possible.

Landscapes

  • Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Public Health (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Optics & Photonics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Vascular Medicine (AREA)
  • Biophysics (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Laser Surgery Devices (AREA)

Abstract

Un appareil de photocoagulation (20) susceptible d'être fixé à une lampe à fente ophtalmique (30) comprend au moins une source laser (1) qui émet une lumière laser thérapeutique dans la direction de l'oeil (31) d'un patient, à travers un diviseur de faisceau (11) monté dans une partie supérieure de l'appareil positionnable entre le microscope (15) d'une lampe à fente et l'oeil du patient. Pendant qu'il utilise l'appareil pour appliquer un traitement, le médecin peut observer l'oeil à travers le microscope de la lampe à fente et le diviseur de faisceau, sans s'exposer à la lumière thérapeutique. Au moins une lentille ajustable ou amovible (14) agencée entre le diviseur de faisceau et l'oeil du patient permet de modifier sélectivement ensemble la distance de focalisation du faisceau laser thérapeutique et du microscope de la lampe à fente devant la partie supérieure de l'appareil. On peut ainsi ajuster l'appareil afin de l'adapter à différentes configurations de lentilles de contact (34) sur l'oeil.
EP19900911809 1989-08-01 1990-08-01 Appareil de photocoagulation Ceased EP0485450A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8917569 1989-08-01
GB898917569A GB8917569D0 (en) 1989-08-01 1989-08-01 Photocoagulation apparatus

Publications (1)

Publication Number Publication Date
EP0485450A1 true EP0485450A1 (fr) 1992-05-20

Family

ID=10660982

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19900911809 Ceased EP0485450A1 (fr) 1989-08-01 1990-08-01 Appareil de photocoagulation

Country Status (5)

Country Link
EP (1) EP0485450A1 (fr)
JP (1) JPH05500315A (fr)
AU (1) AU6061090A (fr)
GB (1) GB8917569D0 (fr)
WO (1) WO1991001703A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027378A1 (fr) * 1996-01-24 1997-07-31 V. Kann Rasmussen Industri A/S Dispositif d'ecran pour ouverture dans un mur

Families Citing this family (15)

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Publication number Priority date Publication date Assignee Title
JP3206923B2 (ja) * 1991-01-30 2001-09-10 株式会社ニデック 眼科用レーザ手術装置
GB9613766D0 (en) * 1996-07-01 1996-09-04 Life Science Resources Ltd Medical laser guidance apparatus
US6344039B1 (en) * 1997-03-18 2002-02-05 Lasersight Technologies, Inc. Device for eliminating parallax of stereo microscopes during refractive laser surgery
GB9717282D0 (en) * 1997-08-14 1997-10-22 Life Science Resources Ltd Medical laser guidance apparatus
JP3807871B2 (ja) 1998-05-28 2006-08-09 株式会社ニデック レーザ治療装置
DE502006005346D1 (de) 2006-07-07 2009-12-24 Od Os Gmbh Ophthalmoskop
DE102008047400B9 (de) * 2008-09-16 2011-01-05 Carl Zeiss Surgical Gmbh Augenchirurgie-Messsystem
US8459795B2 (en) 2008-09-16 2013-06-11 Carl Zeiss Meditec Ag Measuring system for ophthalmic surgery
ITRM20090071A1 (it) * 2009-02-17 2010-08-18 Strumenti Oftalmici C S O S R L Costruzioni Lampada a fessura con uscita laser
EP2301425B1 (fr) * 2009-09-29 2019-11-20 OD-OS GmbH Ophtalmoscope pour l'observation d'un oeil
EP2301424B1 (fr) 2009-09-29 2015-07-08 OD-OS GmbH Ophtalmoscope doté d'un dispositif laser
CN102499631B (zh) * 2011-10-27 2013-12-18 温州医学院眼视光研究院 眼科用单目手持式裂隙灯显微镜
CN103110402B (zh) * 2012-12-19 2015-12-16 苏州康捷医疗股份有限公司 一种可视眼前节检查仪
JP7136471B2 (ja) * 2017-02-09 2022-09-13 ノルレーズ アーペーエス 光熱眼科治療用装置
CN109157188B (zh) * 2018-09-10 2021-10-15 执鼎医疗科技(杭州)有限公司 多人定位微透镜变焦oct光学系统和扫描方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DD137054A1 (de) * 1978-05-10 1979-08-15 Peter Wengler Lichtkoagulator
CH645801A5 (fr) * 1982-03-11 1984-10-31 Lasag Ag Tete optique d'une installation pour l'observation et le traitement par rayonnement laser de l'oeil.
FI79461C (fi) * 1983-08-22 1990-01-10 Lasertek Oy Laseranlaeggning foer oegonoperationer.
EP0293126A1 (fr) * 1987-05-20 1988-11-30 Keeler Limited Appareil de photocoagulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9101703A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027378A1 (fr) * 1996-01-24 1997-07-31 V. Kann Rasmussen Industri A/S Dispositif d'ecran pour ouverture dans un mur

Also Published As

Publication number Publication date
AU6061090A (en) 1991-03-11
JPH05500315A (ja) 1993-01-28
GB8917569D0 (en) 1989-09-13
WO1991001703A1 (fr) 1991-02-21

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