WO2022003682A1 - Intraocular manipulation device - Google Patents

Intraocular manipulation device Download PDF

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Publication number
WO2022003682A1
WO2022003682A1 PCT/IL2021/050798 IL2021050798W WO2022003682A1 WO 2022003682 A1 WO2022003682 A1 WO 2022003682A1 IL 2021050798 W IL2021050798 W IL 2021050798W WO 2022003682 A1 WO2022003682 A1 WO 2022003682A1
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WO
WIPO (PCT)
Prior art keywords
eye
acoustic
additionally
manipulator
combination
Prior art date
Application number
PCT/IL2021/050798
Other languages
French (fr)
Inventor
Shay Roy WERTZBERGER
Adi ABULAFIA
Adam Kenneth HOWARD
Original Assignee
Shaare Zedek Scientific Ltd.
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Filing date
Publication date
Application filed by Shaare Zedek Scientific Ltd. filed Critical Shaare Zedek Scientific Ltd.
Publication of WO2022003682A1 publication Critical patent/WO2022003682A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F9/00—Methods 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
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/00781—Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16—Intraocular lenses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16—Intraocular lenses
    • A61F2002/1681—Intraocular lenses having supporting structure for lens, e.g. haptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0004—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof adjustable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Definitions

  • the present invention pertains to a system and method for manipulating devices and objects inside the eye in a non-invasive manner.
  • Intraocular devices are commonly used in the treatment of several medical conditions, the most common of which is the implantation of an intraocular lens to replace the eye's natural lens in cataract cases.
  • Other intraocular devices include glaucoma treatment devices, sensors (specifically pressure sensors), drug release devices and tension rings. Most of these devices are designed for permanent implantation and do not normally require physical interaction from outside the eye.
  • treatment can benefit from physical manipulation to adjust a property, such as, but not limited to, location, flow rate, and one or more optic properties.
  • Examples of postimplantation manipulation of devices implanted in the eye include manipulation of an intraocular lens (IOL) and adjustment of a shunt implanted to treat glaucoma.
  • IOL intraocular lens
  • IOL transplants and especially toric IOL transplants, require precise placement to align the optical axis of the IOL and the required axis of the patient’s eye.
  • achieving perfect alignment is difficult given the patient’s prone position during implantation and the effect of this position on determining the correct placement axis.
  • adjustment of the lens axis is not carried out unless the error is large.
  • the patient is operated on for a second time to adjust the angle.
  • the ability to rotate the lens postimplantation can improve the refraction outcome for the patient and improve patient satisfaction with the procedure.
  • Aqueous shunts which are implanted in the eye reduce intraocular pressure (IOP) in glaucoma sufferers by draining fluid (aqueous humour) from inside the eye.
  • Shunts have a very small tube (less than ⁇ 1mm) which can become blocked or which may need to be manipulated to change the amount of fluid drained and therefore the IOP.
  • IOP intraocular pressure
  • Shunts have a very small tube (less than ⁇ 1mm) which can become blocked or which may need to be manipulated to change the amount of fluid drained and therefore the IOP.
  • Currently, these cases can only be treated by additional surgery.
  • Manipulation of an aqueous shunt postimplantation in a contactless manner to control IOP, clear out blockages, etc. would be an improvement over current techniques.
  • U.S. Granted Patent No. US10,210,858 to Yoichi Ochiai et al., System and method for manipulating objects in a computational acoustic-potential field discloses a novel system and method based on three-dimensional acoustic-manipulation technology.
  • an acoustic-potential field generated by ultrasonic phased arrays objects can be levitated and animated.
  • Various distributions of acoustic-potential fields can be generated in accordance with the present invention, including acoustic-potential fields having arbitrary shapes, including any three-dimensional shapes.
  • One or more ultrasonic phased arrays surrounding a workspace can be used to generate standing waves of various shapes to provide the acoustic- potential fields.
  • Objects can be suspended at the nodes of the acoustic-potential field so that the ultrasound distribution (i.e., the desired arbitrary shape) is visualized.
  • the system and method can be used to realize floating screen or mid-air raster graphics, mid-air vector graphics, and interaction with levitated objects.
  • the system and method can also be used in other applications, including cleaning applications.
  • US 10,210,858 teaches a plurality of rectangular arrays of ultrasonic transducers, with the objects to be manipulated resting in nodes of the acoustic field generated by the arrays, with movement of the objects being by movement of the nodes.
  • WIPO Patent Application Publication No. WO2017/068435 to Osvaldas Putkis, Contactless Manipulation Apparatus, Assembly Method and 3D Printing discloses an apparatus for contactless manipulation of material and components, such as electronic components, comprised of material and/or component feed devices; acoustic transducer arrays; at least one material and/or component joining (melting, solidifying, welding) device; a base on which an object is formed; and a computing unit with an executable program.
  • the program is used to control acoustic transducers that generate an acoustic field required for particle manipulation.
  • Said control program can receive and process a signal coming from a feedback device in order to estimate the position of material particles or components and improve manipulation accuracy.
  • WO2017/068435 teaches a pair of rectangular arrays facing each other, where the object(s) to be manipulated are positioned between the rectangular arrays.
  • an acoustic manipulator comprising: a base configured to be placed over an eye; a plurality of acoustic transducers attached to the base and arranged in a predetermined pattern, said plurality of acoustic transducers configured to be positioned with emitting faces at least one predetermined distance from a surface of an eye; a processor in communication with said plurality of acoustic transducers, said processor comprising software configured, when activated, to control, for at least one of said transducers, a transducer acoustic wave property selected from a group consisting of a phase, a frequency, an intensity and any combination thereof, for each of said plurality of acoustic transducers, said transducer acoustic wave property is controllable independent of said transducer acoustic wave property of any other of said plurality of acoustic transducers; wherein an acoustic field of a determinable shape, variable with time in
  • an electromagnetic manipulator comprising: abase; a plurality of magnetic sources attached to the base and arranged in a predetermined pattern, said plurality of magnetic sources configured to be positioned at least one predetermined distance from said eye; a processor in communication with said plurality of magnetic sources, said processor comprising software configured, when activated, to control a magnetic field property selected from a group consisting of a polarity, a magnetic field intensity, a magnetic field direction and any combination thereof of at least two of said plurality of magnetic sources, for each of said at least two of said plurality of magnetic sources, said magnetic field property is controllable independent of said magnetic field property of any other of said at least two of said plurality of magnetic sources; wherein a magnetic field of a determinable shape, variable with time in a determinable manner, can be generated within an eye, said magnetic field configured to move an object comprising a magnetic material within the eye in a determinable manner.
  • each of said at least one portion configured to be movable by a magnetic field comprises a material selected from a group consisting of ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
  • each of said plurality of magnetic sources is selected from a group consisting of an electromagnet, a permanent magnet and any combination thereof.
  • FIG. 1 schematically illustrates an ultrasonic manipulator of the present invention
  • Fig. 2 schematically illustrates an electromagnetic manipulator of the present invention
  • Fig. 3 schematically illustrates an exemplary IOL configured to be moved or rotated by an acoustic pressure field
  • Fig. 4 schematically illustrates an exemplary IOL configured to be moved or rotated by an electromagnetic field
  • Fig. 5 schematically illustrates an exemplary intraocular ring system (IRS) configured to be moved or rotated by either an acoustic pressure field or an electromagnetic field; and
  • IMS intraocular ring system
  • Fig. 6 schematically illustrates a glaucoma shunt with a movable shutter.
  • the term 'arrangement' hereinafter refers to a set of objects in a predetermined pattern.
  • the Manipulator has multiple purposes. These include:
  • the Manipulator can be based on manipulation via ultrasonic (acoustic) forces, via magnetic forces, or both.
  • the moving can be in any desired three-dimensional (3D) direction within the eye.
  • 3D three-dimensional
  • an item’s position within the eye can be described by a position ( ⁇ , ⁇ , ⁇ )
  • it can be moved from a position ( ⁇ 1 , ⁇ 1 , ⁇ 1 ) to a position (X 2 ,Y 2 ,Z 2 ) where at least one of the following is true: X 1 ⁇ X 2 , Y 1 ⁇ Y 2 , and Z 1 ⁇ Z 2 .
  • the manipulator is placed on or near the eye.
  • the It comprises at least one ultrasonic transducer.
  • the shape of the acoustic pressure field within the eye is controlled by software that calculates the intensity, frequency and phase of the acoustic radiation to be emitted by each of the transducers.
  • the field can have any shape and is limited only by the number of transducers and their geometric arrangement.
  • each transducer can be controlled, independently of the phase, intensity, frequency and any combination thereof of any other transducer, by software to achieve the desired acoustic pressure field shape.
  • the transducers in the arrangement(s) can be accurately placed at desired locations anywhere on or near the entirety of the exterior of an eye. Therefore, it is possible to accurately generate complex pressure patterns at known positions within the eye.
  • the manipulator can be placed at any location close enough to the eye to allow the generation of the appropriate electromagnetic fields. Typically, it is placed on the head; it can also be placed on or near the eye.
  • the manipulator comprises at least one arrangement of magnetic sources, typically electromagnets.
  • the magnetic sources in the arrangement can be controlled by a computer program to create a magnetic field of any desired size, polarity and direction inside the eye. 4.
  • the magnetic field enables the manipulation of fenous materials or other materials responsive to a magnetic field inside the eye.
  • the magnetic fields are substantially unaffected by the presence of the non-magnetic eye material and the magnetic sources in the arrangement(s) can be accurately placed at desired locations anywhere on or near the entirety of the exterior of an eye it is possible to accurately generate the desired magnetic field shape at known positions, such as the location of magnetic material, within the eye.
  • the transducers create a standing wave in a desired region within the eye, thereby creating high- and low-pressure areas in the region.
  • An object or a portion thereof in the high-pressure area will tend to move from there to the low- pressure area.
  • the locations of the high- and low-pressure areas change, thereby enabling greater control of the movement of the object or portion thereof.
  • the variation in transducer output can be a change in intensity, in phase, in frequency, or any combination thereof.
  • the output of each of the transducers can be changed independently.
  • at least one transducer has a fixed output.
  • the maximum acoustic pressure generated by the transducers is less than about 10 4 Pa.
  • the ultrasound frequency is in the range of about 0.5 MHz to about 10 MHz, preferably in the range 0.8 MHz to 5 MHz.
  • the ultrasound intensity can be in the range of 1 mW/cm 2 to 150 mW/cm 2 . In some embodiments, it is in the range from 10 mW/cm 2 to 100 mW/cm 2 .
  • the magnetic field will typically be in the range of 500 gauss to 3000 gauss, preferably on the order of 1000 gauss
  • Fig. 1 schematically illustrates an ultrasonic manipulator (1000) of the present invention.
  • the ultrasonic manipulator (1000) comprises a base (1100) conformable to the shape of the eye or conformable to the shape of an eyelid that supports an arrangement of ultrasonic transducers (1200) on its inner (eye-facing) side.
  • the ultrasonic manipulator comprises a biocompatible membrane (not shown) on the inner (eye-facing) side of the ultrasonic transducers (1200).
  • a contact layer which can be a liquid layer, a gel layer and any combination thereof, can be used to improve contact.
  • the contact layer is between the ultrasonic transducers (1200) and the eye; components thereof can be on either side of a biocompatible membrane. Similarly, components of the contact layer can be on either side of the eyelid.
  • the ultrasonic manipulator (1000) is in communication with a processor (not shown) comprising software configured to control phase, frequency, intensity and any combination thereof of the individual ultrasonic transducers (1200).
  • the technology embodied by the software enables creation of an acoustic pressure field.
  • the acoustic pressure field is configured to do at least one of the following: exert a force on at least a portion of an object within the eye, exert a force on at least a portion of the eye, exert a force on at least a portion of fluid within the eye, heat at least a portion of an object within the eye, heat at least a portion of the eye, and heat at least a portion of fluid within the eye.
  • the force on an object within the eye can enable a member of a group consisting of: move at least a portion of an object within the eye, rotate at least a portion of an object within the eye, linearly move at least a portion of the eye, angularly move at least a portion of an eye, linearly move at least a portion of the fluid within the eye, angularly move at least a portion of fluid within the eye and any combination thereof.
  • the moved object can be an intraocular lens (IOL) or a portion thereof, a ring in an intraocular ring system (IRS) or a portion thereof, a support or other component of an IRS, a glaucoma shunt or a portion thereof, an implantable miniature telescope for macular degeneration or a portion thereof, a retinal chip, a sensor, a blockage and any combination thereof.
  • IOL intraocular lens
  • IRS intraocular ring system
  • a support or other component of an IRS a glaucoma shunt or a portion thereof
  • an implantable miniature telescope for macular degeneration or a portion thereof a retinal chip
  • a sensor a sensor
  • a blockage can be a blockage of a shunt or an item blocking a light path.
  • blockages include a blood clot, a deposit in the eye such as a floater, a deposit in the eye such as hardened material which has separated from an object inserted in the eye, a remnant from a medical procedure and a fragment separated from an object in the eye.
  • Fig. 2 schematically illustrates an electromagnetic manipulator (2000) of the present invention.
  • the magnetic manipulator (2000) is configured to rest on or near the eye. It comprises a base (2100) which supports an arrangement of electromagnets (2200) on its inner (eye-facing) side.
  • the electromagnets (2200) are close enough to the eye to enable the transfer of a predetermined electromagnetic field to the inside of the eye.
  • the base and attached electromagnets can be mounted anywhere on the head, for non-limiting example, on the forehead, on a cheek, on the top of the head, on the rear of the head, on the neck and any combination thereof.
  • the electromagnetic manipulator (2000) is in communication with a processor (not shown) comprising software configured to control intensity, polarity and direction of the field generated by the individual electromagnets (2200).
  • the technology embodied by the software enables creation of a magnetic field configured to do at least one of the following: exert a force on at least a portion of an object within the eye and heat at least a portion of an object within the eye.
  • the force on an object within the eye can enable a member of a group consisting of: move at least a portion of an object within the eye, rotate at least a portion of an object within the eye and any combination thereof.
  • the moved object can be an IOL or a portion thereof, a ring in an IRS or a portion thereof, a glaucoma shunt or a portion thereof, an implantable miniature telescope for macular degeneration or a portion thereof, a retinal chip, a sensor, and any combination thereof.
  • Fig. 3 illustrates an exemplary IOL (3000) configured to be moved or rotated by an acoustic pressure field.
  • the IOL is of a standard type, comprising a lens (3010) and two haptics (3020).
  • each of the haptics (3020) comprises an area (3030) configured to accept a pressure difference and translate it into a member of a group consisting of a force to move the lens, a torque to rotate the lens and any combination thereof.
  • the area (3030) configured to accept a pressure difference can be mounted on or be part of other designs of IOL.
  • the area (3030) configured to accept a pressure difference can be mounted on one or more haptics (3020), on the lens (3010) and any combination thereof.
  • the pressure difference acts directly on the object to be moved or a portion thereof.
  • the object to be moved or the portion thereof additionally comprises an area configured to accept a pressure difference. In some variants of such embodiments, no additional pressure-accepting area is present.
  • Fig. 4 illustrates an exemplary IOL (4000) configured to be moved or rotated by a magnetic field.
  • the IOL is of a standard type, comprising a lens (4010) and two haptics (4020).
  • each of the haptics (4020) comprises an area (4020) configured to react to a magnetic field and translate it into a member of a group consisting of a force to move the lens, a torque to rotate the lens and any combination thereof.
  • the area (4020) configured to react to a magnetic field comprises a magnetizable material such as ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
  • the area (4030) configured to accept a magnetic field can be mounted on or part of other designs of IOL.
  • the area (4030) configured to accept a magnetic force can be mounted on one or more haptics (4020), on the lens (4010) and any combination thereof.
  • Fig. 5 schematically illustrates an IRS (5000) configured to be movable by either an acoustic manipulator or an electromagnetic manipulator.
  • the IRS (5000) comprises two rings, primary intraocular ring (PIR) (5300) and a secondary device (SD) (5200).
  • An exemplary haptic IOL (5100) is supported by the SD (5200).
  • the exemplary IOL (5100) comprises a lens (5110) and two haptics (5120).
  • the exemplary PIR (5300) comprises two tabs (5330), while the exemplary SD (5200) comprises three tabs (5230), two of them visible in the figure.
  • a tab will comprise magnetic material whereas, for an acoustic manipulator, a tab can be of any desired material and will typically be of the same material as the component to which it is attached.
  • the tabs (5330) of the PIR (5300) are on an outward face of the PIR (5300), facing toward the exterior of the eye, while the tabs (5230) of the SD (5200) are at the back of the SD (5200) and face inward towards the center of IRS (5000).
  • the tabs can be at any position that does not interfere with the movement of the components of the IRS (5000).
  • a PIR (5300) configured for use with an electromagnetic manipulator
  • at least a portion of the PIR (5300) comprises magnetic material and the PIR (5300) has no tabs.
  • the SD (5200) has no tabs.
  • acoustic pressure on an IOL guide (5240) can move the SD (5200), while, for an electromagnetic manipulator, at least a portion of the SD (5200) comprises magnetic material.
  • the IOL (5100) does not comprise tabs.
  • the IOL (5100) For an acoustic manipulator, is can be moved directly by acoustic pressure, whereas, for an electromagnetic manipulator, at least a portion of the IOL (5100) comprises magnetic material.
  • the IOL (5100) comprises at least one tab.
  • Fig. 6 schematically illustrates a glaucoma shunt (6000) with a movable shutter (6200) configured to reversibly cover at least a portion of a port (6100) of the shunt (6000).
  • the shutter (6200) comprises a cover (6210) and a tab (6220).
  • the shutter (6200) can be moved by applying a pressure difference to the tab (6220) or, if the shutter (6200) comprises a magnetizable material, by applying a magnetic field to either the tab (6220) or the cover (6210).
  • the effective flow through the shunt (6000) can be changed according to the patient’s needs.
  • the shunt itself can be repositioned, either magnetically or acoustically, to improve its position in the eye. Movement of the shunt (6000) can be induced magnetically, acoustically and any combination thereof. Movement of the shutter (6200) can be induced magnetically, acoustically and any combination thereof.
  • the means of inducing movement of the shunt (6000) need not be the same as the means of inducing movement of the shutter (6200).
  • the ultrasonic manipulator can remove matter from a glaucoma shunt, for non-limiting example, by inducing the matter to move towards the end of the shunt furthest from the interior of the eye.
  • a manipulator can alter at least one attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
  • the attribute can be a material property of a nanoparticle, a position of a nanoparticle, and any combination thereof.
  • behavior of the lens can be altered, for example, by changing the refractive index of at least a portion of the lens, by changing the degree of lens toricity, by changing the toric axis of the lens, and any combination thereof.
  • the refractive index of a portion of the lens By changing the refractive index of a portion of the lens, the amount of multifocality of the lens is altered.
  • the material property of the nanoparticle can be its refractive index, its shape and any combination thereof.
  • a manipulator can change the rate of delivery of drug by at least partially opening or at least partially closing a shunt of a slow release drug delivery system.
  • the at least partially opening and the at least partially closing of the shunt are reversible.
  • the acoustic manipulator is further configured to map a member of a group consisting of the shape of at least a portion of the eye, the size of at least a portion of the eye, the shape of at least a portion of an object in the eye, the size of at least a portion of an object in the eye and any combination thereof.
  • the acoustic manipulator can map a member of a group selected from at least a portion of the interior of the eye, the location of at least a portion of an object in the interior of the eye and any combination thereof.
  • the electromagnetic manipulator can, for objects comprising material responsive to an electromagnetic field, map the location of at least a portion of at least one such object in the interior of the eye.
  • An IRS can be rotated using radiation force, a nonlinear effect proportional to the acoustic wave amplitude, thus creating a continuous, non-oscillating force for a stimulus of a constant amplitude [Rudenko OV, Sarvazyan AP, Emelianov SY, (1996) Acoustic radiation force and streaming induced by focused nonlinear ultrasound in a dissipative medium. J Acoust Soc AM 99:2791- 2798. Doi: 10.1121/1.414805].
  • This nonlinear effect obtained implies the induction of a “constant” positive average pressure, induced by the wave along its propagation direction. When encountering a reflective surface, this radiation pressure induces radiation force [H. Azhari, Basics of biomedical ultrasound for engineers. 2010, Wiley: IEEE: Hoboken, N.J].
  • an object in the wave path that absorbs or reflects sound energy is subjected to a force, the acoustic radiation force, from the acoustic radiation.
  • the ultrasound system can comprise a phased array integrated therapeutic-imaging transducer, a programmable ultrasound system, a function signal generator and an amplifier.
  • the integrated therapeutic-imaging transducer combined both a 64-element therapeutic phased array probe and a B-mode ultrasound imaging probe.
  • the phased array transducer was constructed with piezoelectric elements.
  • the therapeutic probe elements were arranged in rings that were regularly arranged on the outer surface area of the integrated transducer.
  • the radiation force needed to rotate the ocular implant was generated by the therapeutic probe.
  • the center frequency of the therapeutic probe elements was on the order of hundreds of kHz.
  • imaging B-mode probe that was in the central circular hole of the spherical integrated transducer enabled the system to monitor the rotation of the implant, creating closed feed-back to the therapeutic probe.
  • imaging transducers center frequency is generally in order of few MHz such that a good resolution is obtained.
  • the programmable ultrasound system allowed control of both parts of the transducer independently and simultaneously.
  • the therapeutic part of the transducer was dynamically focused through a focusing method known as “electronic focusing”, where, both the amplitude and the phase of the electrical signal that excited each element of the phased array are independently controlled by the ultrasound programmable system so that the delay of each element’s transmission is controllable.
  • the control of the delay after each element is excited allowed the synthetically generation of a point of constructive interference of all the elements’ excitation signal and thus allowed steering of the focal point to any point in space.
  • the delays are geometrically calculated using the following formula: (1) where ⁇ i represents the delay of element i, x c , y c , z c are the coordinates of the furthest element from the focus point, x f , y f , z f are the coordinates of the focus point and x i , y i , z i are the coordinates of element i. it has to be noted that all these time values are calculated relative to a defined point on the aperture.
  • the programmable ultrasound system allows simultaneous control of the imaging part of the transducer in order to track the motion of the implant caused by the radiation force. Moreover, the ultrasound programmable system allows triggering of the function signal generator in order to excite each of the array’s elements.
  • the function signal generator also called the waveform generator, generates different types of electrical waveforms over a large variety of frequencies and amplitudes. Some of the most common waveforms produced by the function generator are sine wave, square wave, triangular wave and sawtooth shapes. These waveforms can be either repetitive or single-shot and require either an internal or an external trigger source which, in this case, was given via the ultrasound programmable system.
  • the prototype of the intraocular implant is made of two concentric rings.
  • the inner ring has two arms extending from it to receive ultrasound pressure and initiate movement.
  • the cross section of the surface on which the ultrasound is received is 1.25 mm X 0.8 mm.
  • the cross-sectional area of the focal point is defined by the full width at half maximum (FWHM) formula.
  • the Food and Drug Administration (FDA) and World Federation for Ultrasound in Medicine and Biology have imposed strict thermal index (TI) and mechanical index (MI) limits for ocular applications.
  • the MI is a safety indicator related to mechanical effects, such as cavitation, of the sequence transmission while the TI gives a rough estimate of the risks resulting from undesired thermal effects.
  • the FDA and World Federation for Ultrasound in Medicine and Biology TI limit is TI ⁇ 1.0 and the MI limit is MI ⁇ 0.23.
  • TIS is the thermal index of soft tissue
  • W 01 is the maximum value of the time averaged acoustic output power emitted from any 1-cm length of the radiating aperture in the scan direction in mW
  • f c is the center frequency in MHz.
  • the voltage and the frequency of the excitation for each array’s element will be chosen such that it allows motion of the implant while respecting the safety limitations of ocular applications as determined by the FDA.
  • three different ultrasound sequence modes need to be considered - (a) without focusing when in non-scanning mode and, when in a scanning mode, either focused or steered, so that it can be assumed that most of the energy field is near the transducer; (b) plane waves in non-scanning mode where it can be assumed that most of the energy field is near the transducer; and (c) a non-scanning mode with focusing, where it can be assumed that most of the energy field is at the focus.
  • mode (c) is the more appropriate.
  • the cross section at the focal point has to be estimated, generally through the FWHM formula at the focus depth. If the cross section at the focal point is smaller than 1 cm 2 , then the power parameter W 0 will represent the total output power from the ultrasound source. Otherwise, W 0 will be calculated in the smaller cross-sectional area of 1 cm 2 through the cumulative temporally averaged intensity, I SPTA .
  • c is the acoustic velocity in soft tissue, assumed to be z is the focal depth and d trans is the aperture width, in this case, the outer diameter of the phased array transducer.
  • the diameter of the cross section obtained at the focal depth is
  • the thermal index TI exceeds the FDA limit.
  • the TI can be reduced by reducing the total power Wo, by reducing the central frequency f c , by pulsing the power sufficiently to allow cooling, and by any combination thereof.
  • the proof-of-concept experiment demonstrates that an object of over 50 times the weight of an implant can be controllably moved by shaped ultrasonic radiation, with an acceptable MI and a TI close to the safe limit, showing that safe, controllable movement of an implant within an eye is most probable.

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Abstract

An acoustic manipulator for controllably moving an object within an eye. The acoustic manipulator comprises a base fitting over an eye, a plurality of acoustic transducers emitting towards the eye, attached to the base and arranged in a predetermined pattern, and a processor in communication with the plurality of acoustic transducers. The processor independently controls, for each transducer, emission properties such as phase, frequency and intensity, thereby generating within the eye an acoustic field of a determinable shape and magnitude, variable with time in a determinable manner, which can controllably move an object within the eye.

Description

INTRAOCULAR MANIPULATION DEVICE
FIELD OF THE INVENTION
The present invention pertains to a system and method for manipulating devices and objects inside the eye in a non-invasive manner.
BACKGROUND OF THE INVENTION
Intraocular devices are commonly used in the treatment of several medical conditions, the most common of which is the implantation of an intraocular lens to replace the eye's natural lens in cataract cases. Other intraocular devices include glaucoma treatment devices, sensors (specifically pressure sensors), drug release devices and tension rings. Most of these devices are designed for permanent implantation and do not normally require physical interaction from outside the eye.
However, in some cases, treatment can benefit from physical manipulation to adjust a property, such as, but not limited to, location, flow rate, and one or more optic properties.
Examples of postimplantation manipulation of devices implanted in the eye include manipulation of an intraocular lens (IOL) and adjustment of a shunt implanted to treat glaucoma.
IOL transplants, and especially toric IOL transplants, require precise placement to align the optical axis of the IOL and the required axis of the patient’s eye. However, achieving perfect alignment is difficult given the patient’s prone position during implantation and the effect of this position on determining the correct placement axis. Additionally, there is often a degree of lens rotation during the healing process. In current practice, adjustment of the lens axis is not carried out unless the error is large. In these extreme cases, the patient is operated on for a second time to adjust the angle. In cases where the lens axis is different from the desired axis, the ability to rotate the lens postimplantation can improve the refraction outcome for the patient and improve patient satisfaction with the procedure.
Aqueous shunts which are implanted in the eye reduce intraocular pressure (IOP) in glaucoma sufferers by draining fluid (aqueous humour) from inside the eye. Shunts have a very small tube (less than ~1mm) which can become blocked or which may need to be manipulated to change the amount of fluid drained and therefore the IOP. Currently, these cases can only be treated by additional surgery. Manipulation of an aqueous shunt postimplantation in a contactless manner to control IOP, clear out blockages, etc., would be an improvement over current techniques.
Physical manipulation of these devices post-implantation is generally invasive, requiring some degree of surgery, and is therefore complex, increasing the patient’s risk of surgery-related complications (e.g., infections, surgical errors, etc.) and requiring costly surgical suites.
External, non-invasive manipulation of intraocular devices through the use of contactless force(s) such as, but not limited to, acoustic potential fields and magnetic forces, can be a substantial improvement over current surgically induced manipulation in that it can be more precise in its manipulative capabilities as well as avoid the risks and costs associated with surgery, the subsequent healing process, and the patient’s natural agitation and worry on undergoing another surgical procedure.
U.S. Granted Patent No. US10,210,858 to Yoichi Ochiai et al., System and method for manipulating objects in a computational acoustic-potential field, discloses a novel system and method based on three-dimensional acoustic-manipulation technology. By changing the distribution of an acoustic-potential field generated by ultrasonic phased arrays, objects can be levitated and animated. Various distributions of acoustic-potential fields can be generated in accordance with the present invention, including acoustic-potential fields having arbitrary shapes, including any three-dimensional shapes. One or more ultrasonic phased arrays surrounding a workspace can be used to generate standing waves of various shapes to provide the acoustic- potential fields. Objects can be suspended at the nodes of the acoustic-potential field so that the ultrasound distribution (i.e., the desired arbitrary shape) is visualized. The system and method can be used to realize floating screen or mid-air raster graphics, mid-air vector graphics, and interaction with levitated objects. The system and method can also be used in other applications, including cleaning applications.
However, US 10,210,858 teaches a plurality of rectangular arrays of ultrasonic transducers, with the objects to be manipulated resting in nodes of the acoustic field generated by the arrays, with movement of the objects being by movement of the nodes.
WIPO Patent Application Publication No. WO2017/068435 to Osvaldas Putkis, Contactless Manipulation Apparatus, Assembly Method and 3D Printing, discloses an apparatus for contactless manipulation of material and components, such as electronic components, comprised of material and/or component feed devices; acoustic transducer arrays; at least one material and/or component joining (melting, solidifying, welding) device; a base on which an object is formed; and a computing unit with an executable program. The program is used to control acoustic transducers that generate an acoustic field required for particle manipulation. Said control program can receive and process a signal coming from a feedback device in order to estimate the position of material particles or components and improve manipulation accuracy.
However, WO2017/068435 teaches a pair of rectangular arrays facing each other, where the object(s) to be manipulated are positioned between the rectangular arrays.
It is therefore a long felt need to provide a system and method of contactless manipulation which does not require a plurality of rectangular arrays of transducers.
SUMMARY OF THE INVENTION
It is an object of the present invention to disclose a system and method for manipulating devices and objects inside the eye in a non-invasive manner.
It is another object of the present invention to disclose an acoustic manipulator, comprising: a base configured to be placed over an eye; a plurality of acoustic transducers attached to the base and arranged in a predetermined pattern, said plurality of acoustic transducers configured to be positioned with emitting faces at least one predetermined distance from a surface of an eye; a processor in communication with said plurality of acoustic transducers, said processor comprising software configured, when activated, to control, for at least one of said transducers, a transducer acoustic wave property selected from a group consisting of a phase, a frequency, an intensity and any combination thereof, for each of said plurality of acoustic transducers, said transducer acoustic wave property is controllable independent of said transducer acoustic wave property of any other of said plurality of acoustic transducers; wherein an acoustic field of a determinable shape, variable with time in a determinable manner, can be generated within an eye, said acoustic field configured to alter at least one property of an item within the eye in a determinable manner.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said predetermined distance is zero.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said predetermined distance is a thickness of an eyelid.
It is another object of the present invention to disclose the acoustic manipulator as described above, additionally comprising a contact material selected from a group consisting of a biocompatible membrane, a liquid, a gel and any combination thereof in contact with said plurality of acoustic transducers.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said predetermined distance is a thickness of said contact material.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said item is selected from a group consisting of an object within the eye, a portion of the eye, and fluid within the eye.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said object within the eye is selected from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a blockage and any combination thereof.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said object within the eye comprises at least one tab configured to be movable by a force exerted by an acoustic field.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said alteration of said property is selected from a group consisting of linearly moving at least a portion of said item, rotating at least a portion of said item, heating at least a portion of said item, and any combination thereof.
It is another object of the present invention to disclose the acoustic manipulator as described above, additionally configured to measure an eye property selected from a group consisting of a shape of at least a portion of the eye, a size of at least a portion of the eye, a shape of at least a portion of an object in the eye, a size of at least a portion of an object in the eye and any combination thereof. It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said transducer acoustic wave property is at least partly dependent on said measured eye property.
It is another object of the present invention to disclose the acoustic manipulator as described above, additionally configured to map a member selected from a group consisting of at least a portion of an interior of the eye, a location of at least a portion of an object in the eye and any combination thereof.
It is another object of the present invention to disclose the acoustic manipulator as described above, additionally configured to change an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said attribute is selected from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein said material property of the nanoparticle is selected from a group consisting of refractive index, shape and any combination thereof.
It is another object of the present invention to disclose the acoustic manipulator as described above, additionally configured to perform an action selected from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the maximum acoustic pressure generated by the transducers is less than 104 Pa.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the ultrasound frequency is in a range of 0.5 MHz to 10 MHz.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the ultrasound frequency is in a range of 0.8 MHz to 5 MHz.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the ultrasound intensity is in the range of 1 mW/cm2 to 150 mW/cm2.
It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the ultrasound intensity is in a range of 10 mW/cm2 to 100 mW/cm2. It is another object of the present invention to disclose the acoustic manipulator as described above, wherein the base has a shape conformable to the eye.
It is another object of the present invention to disclose an electromagnetic manipulator, comprising: abase; a plurality of magnetic sources attached to the base and arranged in a predetermined pattern, said plurality of magnetic sources configured to be positioned at least one predetermined distance from said eye; a processor in communication with said plurality of magnetic sources, said processor comprising software configured, when activated, to control a magnetic field property selected from a group consisting of a polarity, a magnetic field intensity, a magnetic field direction and any combination thereof of at least two of said plurality of magnetic sources, for each of said at least two of said plurality of magnetic sources, said magnetic field property is controllable independent of said magnetic field property of any other of said at least two of said plurality of magnetic sources; wherein a magnetic field of a determinable shape, variable with time in a determinable manner, can be generated within an eye, said magnetic field configured to move an object comprising a magnetic material within the eye in a determinable manner.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said base has a shape conformable to the eye.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said base is configured to be placed over an eye.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said predetermined distance is zero.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, additionally comprising a biocompatible membrane in contact with said plurality of magnetic sources.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said predetermined distance is the thickness of said membrane.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said object within the eye is selected from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a remnant from a medical procedure, a fragment separated from an object in the eye and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said object within the eye comprises at least one portion configured to be movable by a magnetic field.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein each of said at least one portion configured to be movable by a magnetic field comprises a material selected from a group consisting of ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said alteration of said property is selected from a group consisting of linearly moving at least a portion of said object, rotating at least a portion of said object, heating at least a portion of said object, and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein each of said plurality of magnetic sources is selected from a group consisting of an electromagnet, a permanent magnet and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above additionally configured to map a location of at least a portion of at least one object in an interior of the eye.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, additionally configured to change an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said attribute is selected from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein said material property of the nanoparticle is selected from a group consisting of refractive index, shape and any combination thereof.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, additionally configured to perform an action selected from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein the magnetic field is in a range of 500 gauss to 3000 gauss.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein the magnetic field is in a range of 800 gauss to 1500 gauss.
It is another object of the present invention to disclose the electromagnetic manipulator as described above, wherein the magnetic field is 1000 gauss.
It is another object of the present invention to disclose a method of manipulating items within an eye, comprising steps of: providing an acoustic manipulator, comprising: a base configured to be placed over an eye; a plurality of acoustic transducers attached to the base and arranged in a predetermined pattern, said plurality of acoustic transducers configured to be positioned with emitting faces at at least one predetermined distance from a surface of an eye; a processor in communication with said plurality of acoustic transducers, said processor comprising software configured, when activated, to control, for at least one of said transducers, a transducer acoustic wave property selected from a group consisting of a phase, a frequency, an intensity and any combination thereof, for each of said plurality of acoustic transducers, said transducer acoustic wave property is controllable independent of said transducer acoustic wave property of any other of said plurality of acoustic transducers; positioning said acoustic manipulator on an eye; by means of said software, determining said phase and said intensity for each of said plurality of acoustic transducers, for each of said plurality of acoustic transducers, said phase and said intensity being either fixed in time or varying in time; activating each of said plurality of acoustic transducers according to said phase and said intensity; generating within the eye an acoustic field of a determinable shape, variable with time in a determinable manner; thereby altering at least one property of an item within the eye in a determinable manner.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of setting said predetermined distance to zero.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of setting said predetermined distance to a thickness of an eyelid.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing a contact material selected from a group consisting of biocompatible membrane, a liquid, a gel and any combination thereof in contact with said plurality of acoustic transducers.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of setting said predetermined distance to be a thickness of said contact material. It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said item from a group consisting of an object within the eye, a portion of the eye, and fluid within the eye.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said object within the eye from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a blockage and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing said object within the eye comprising at least one tab, said tab configured to be movable by a force exerted by an acoustic field.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said alteration of said property from a group consisting of linearly moving at least a portion of said item, rotating at least a portion of said item, heating at least a portion of said item, and any combination thereof. It is another object of the present invention to disclose the method as described above, additionally comprising a step of measuring an eye property selected from a group consisting of a shape of at least a portion of the eye a size of at least a portion of the eye, a shape of at least a portion of an object in the eye, a size of at least a portion of an object in the eye and any combination thereof.
It is another object of the present invention to disclose the method as described above, wherein said transducer acoustic wave property is at least partly dependent on said measured eye property. It is another object of the present invention to disclose the method as described above, additionally comprising a step of mapping a member of a group selected from at least a portion of an interior of the eye, a location of at least a portion of an object in the eye and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of changing an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said attribute from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said material property of the nanoparticle from a group consisting of refractive index, shape and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting an action from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system. It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the maximum acoustic pressure generated by the transducers to be less than 104Pa.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the ultrasound frequency to be in a range of 0.5 MHz to 10 MHz.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the ultrasound frequency to be in a range of 0.8 MHz to 5 MHz.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the ultrasound intensity to be in the range of 1 mW/cm2 to 150 mW/cm2.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the ultrasound intensity to be in a range of 10 mW/cm2 to 100 mW/cm2.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing the base having a shape conformable to the eye.
It is another object of the present invention to disclose a method of manipulating items within an eye, comprising steps of: providing a magnetic manipulator, comprising: abase; a plurality of magnetic sources attached to the base and arranged in a predetermined pattern, said plurality of magnetic sources configured to be positioned at at least one predetermined distance from said eye; a processor in communication with said plurality of magnetic sources, said processor comprising software configured, when activated, to control a magnetic field property selected from a group consisting of a polarity, a magnetic field intensity, a magnetic field direction and any combination thereof of at least two of said plurality of magnetic sources, for each of said at least two of said plurality of magnetic sources, said magnetic field property is controllable independent of said magnetic field property of any other of said at least two of said plurality of magnetic sources; positioning said magnetic manipulator at said at least one predetermined distance from said eye; by means of said software, determining said magnetic field property for each of said plurality of magnetic transducers, for each of said plurality of magnetic transducers, said magnetic field property being either fixed in time or varying in time; activating each of said plurality of magnetic transducers according to said determined magnetic field property; generating within the eye a magnetic field of a determinable shape, variable with time in a determinable manner; thereby moving within the eye in a determinable manner an object comprising a magnetic material.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing said base conformable to a shape of said eye.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of placing said base over said eye.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of setting said predetermined distance to zero.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing a biocompatible membrane in contact with said plurality of magnetic sources.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of setting said predetermined distance to be the thickness of said membrane.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said object within the eye is a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a remnant from a medical procedure, a fragment separated from an object in the eye and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of providing said object within the eye comprising at least one portion configured to be movable by a magnetic field.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting each of said at least one portion configured to be movable by a magnetic field comprising a material from a group consisting of ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said alteration of said property from a group consisting of linearly moving at least a portion of said object, rotating at least a portion of said object, heating at least a portion of said object, and any combination thereof. It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting each of said plurality of magnetic sources from a group consisting of an electromagnet, a permanent magnet and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of mapping a location of at least a portion of at least one object in an interior of the eye.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of changing an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said attribute from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting said material property of the nanoparticle from a group consisting of refractive index, shape and any combination thereof.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting an action from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system. It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the magnetic field to be in a range of 500 gauss to 3000 gauss.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the magnetic field to be in a range of 800 gauss to 1500 gauss.
It is another object of the present invention to disclose the method as described above, additionally comprising a step of selecting the magnetic field to be 1000 Gauss.
BRIEF DESCRIPTION OF THE FIGURES
In order to better understand the invention and its implementation in practice, a plurality of embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, wherein Fig. 1 schematically illustrates an ultrasonic manipulator of the present invention;
Fig. 2 schematically illustrates an electromagnetic manipulator of the present invention;
Fig. 3 schematically illustrates an exemplary IOL configured to be moved or rotated by an acoustic pressure field;
Fig. 4 schematically illustrates an exemplary IOL configured to be moved or rotated by an electromagnetic field;
Fig. 5 schematically illustrates an exemplary intraocular ring system (IRS) configured to be moved or rotated by either an acoustic pressure field or an electromagnetic field; and
Fig. 6 schematically illustrates a glaucoma shunt with a movable shutter.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of said invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, will remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide a means and method for manipulating devices and objects inside the eye in a non-invasive manner.
The term 'arrangement' hereinafter refers to a set of objects in a predetermined pattern.
The Manipulator has multiple purposes. These include:
• Exerting one or more forces on at least one object inside the eye in a non-invasive manner.
• Linearly moving at least one object inside the eye, rotating at least one object inside the eye, or both, in a non-invasive manner;
• Exerting one or more forces on at least one part of the eye in a non-invasive manner;
• Moving fluid within the eye in a non-invasive manner, either linearly or rotationally; and
• Heating at least a portion of at least one object within the eye in a non-invasive manner;
• Heating at least a portion of at least one part of the eye in a non-invasive manner; and
• Selectively heating at least a portion of fluid within the eye in a non-invasive manner. The Manipulator can be based on manipulation via ultrasonic (acoustic) forces, via magnetic forces, or both.
The moving, either linear or rotational, can be in any desired three-dimensional (3D) direction within the eye. For non-limiting example, if an item’s position within the eye can be described by a position (Χ,Υ,Ζ), then it can be moved from a position (Χ1,Υ1,Ζ1) to a position (X2,Y2,Z2) where at least one of the following is true: X1≠X2, Y1≠Y2, and Z1≠Z2.
For an ultrasonic manipulator:
1. The manipulator is placed on or near the eye.
2. It comprises at least one ultrasonic transducer.
3. The shape of the acoustic pressure field within the eye is controlled by software that calculates the intensity, frequency and phase of the acoustic radiation to be emitted by each of the transducers.
4. The field can have any shape and is limited only by the number of transducers and their geometric arrangement.
5. The phase, intensity, frequency and any combination thereof of each transducer can be controlled, independently of the phase, intensity, frequency and any combination thereof of any other transducer, by software to achieve the desired acoustic pressure field shape.
6. Since the exterior of the eye is substantially a portion of a sphere, the transducers in the arrangement(s) can be accurately placed at desired locations anywhere on or near the entirety of the exterior of an eye. Therefore, it is possible to accurately generate complex pressure patterns at known positions within the eye.
For a magnetic manipulator:
1. The manipulator can be placed at any location close enough to the eye to allow the generation of the appropriate electromagnetic fields. Typically, it is placed on the head; it can also be placed on or near the eye.
2. The manipulator comprises at least one arrangement of magnetic sources, typically electromagnets.
3. The magnetic sources in the arrangement can be controlled by a computer program to create a magnetic field of any desired size, polarity and direction inside the eye. 4. The magnetic field enables the manipulation of fenous materials or other materials responsive to a magnetic field inside the eye.
5. Since the magnetic fields are substantially unaffected by the presence of the non-magnetic eye material and the magnetic sources in the arrangement(s) can be accurately placed at desired locations anywhere on or near the entirety of the exterior of an eye it is possible to accurately generate the desired magnetic field shape at known positions, such as the location of magnetic material, within the eye.
In preferred embodiments of an ultrasonic manipulator, the transducers create a standing wave in a desired region within the eye, thereby creating high- and low-pressure areas in the region. An object or a portion thereof in the high-pressure area will tend to move from there to the low- pressure area. In some embodiments, as the transducer outputs are varied, the locations of the high- and low-pressure areas change, thereby enabling greater control of the movement of the object or portion thereof.
The variation in transducer output can be a change in intensity, in phase, in frequency, or any combination thereof. In preferred embodiments, the output of each of the transducers can be changed independently. In some, less preferred embodiments, there is at least one plurality of transducers in which all of the transducers therein change in concert. In some less preferred embodiments, at least one transducer has a fixed output.
The maximum acoustic pressure generated by the transducers is less than about 104 Pa.
The ultrasound frequency is in the range of about 0.5 MHz to about 10 MHz, preferably in the range 0.8 MHz to 5 MHz.
The ultrasound intensity can be in the range of 1 mW/cm2 to 150 mW/cm2. In some embodiments, it is in the range from 10 mW/cm2 to 100 mW/cm2.
For magnetic manipulators, the magnetic field will typically be in the range of 500 gauss to 3000 gauss, preferably on the order of 1000 gauss
For both the ultrasonic manipulator and the magnetic manipulator, linear movement, rotational movement and any combination thereof can be generated.
Fig. 1 schematically illustrates an ultrasonic manipulator (1000) of the present invention. The ultrasonic manipulator (1000) comprises a base (1100) conformable to the shape of the eye or conformable to the shape of an eyelid that supports an arrangement of ultrasonic transducers (1200) on its inner (eye-facing) side. In some embodiments, the ultrasonic manipulator comprises a biocompatible membrane (not shown) on the inner (eye-facing) side of the ultrasonic transducers (1200). In some embodiments, a contact layer, which can be a liquid layer, a gel layer and any combination thereof, can be used to improve contact. The contact layer is between the ultrasonic transducers (1200) and the eye; components thereof can be on either side of a biocompatible membrane. Similarly, components of the contact layer can be on either side of the eyelid.
Contact between the ultrasonic transducers (1200) and the eye enables the transfer of ultrasonic waves to the inside of the eye. The ultrasonic manipulator (1000) is in communication with a processor (not shown) comprising software configured to control phase, frequency, intensity and any combination thereof of the individual ultrasonic transducers (1200). The technology embodied by the software enables creation of an acoustic pressure field. The acoustic pressure field is configured to do at least one of the following: exert a force on at least a portion of an object within the eye, exert a force on at least a portion of the eye, exert a force on at least a portion of fluid within the eye, heat at least a portion of an object within the eye, heat at least a portion of the eye, and heat at least a portion of fluid within the eye.
The force on an object within the eye can enable a member of a group consisting of: move at least a portion of an object within the eye, rotate at least a portion of an object within the eye, linearly move at least a portion of the eye, angularly move at least a portion of an eye, linearly move at least a portion of the fluid within the eye, angularly move at least a portion of fluid within the eye and any combination thereof.
The moved object can be an intraocular lens (IOL) or a portion thereof, a ring in an intraocular ring system (IRS) or a portion thereof, a support or other component of an IRS, a glaucoma shunt or a portion thereof, an implantable miniature telescope for macular degeneration or a portion thereof, a retinal chip, a sensor, a blockage and any combination thereof.
A blockage can be a blockage of a shunt or an item blocking a light path. Non-limiting examples of blockages include a blood clot, a deposit in the eye such as a floater, a deposit in the eye such as hardened material which has separated from an object inserted in the eye, a remnant from a medical procedure and a fragment separated from an object in the eye. Fig. 2 schematically illustrates an electromagnetic manipulator (2000) of the present invention. In the embodiment shown, the magnetic manipulator (2000) is configured to rest on or near the eye. It comprises a base (2100) which supports an arrangement of electromagnets (2200) on its inner (eye-facing) side. The electromagnets (2200) are close enough to the eye to enable the transfer of a predetermined electromagnetic field to the inside of the eye. In other embodiments, the base and attached electromagnets can be mounted anywhere on the head, for non-limiting example, on the forehead, on a cheek, on the top of the head, on the rear of the head, on the neck and any combination thereof.
The electromagnetic manipulator (2000) is in communication with a processor (not shown) comprising software configured to control intensity, polarity and direction of the field generated by the individual electromagnets (2200). The technology embodied by the software enables creation of a magnetic field configured to do at least one of the following: exert a force on at least a portion of an object within the eye and heat at least a portion of an object within the eye.
The force on an object within the eye can enable a member of a group consisting of: move at least a portion of an object within the eye, rotate at least a portion of an object within the eye and any combination thereof.
The moved object can be an IOL or a portion thereof, a ring in an IRS or a portion thereof, a glaucoma shunt or a portion thereof, an implantable miniature telescope for macular degeneration or a portion thereof, a retinal chip, a sensor, and any combination thereof.
Fig. 3 illustrates an exemplary IOL (3000) configured to be moved or rotated by an acoustic pressure field. The IOL is of a standard type, comprising a lens (3010) and two haptics (3020). In this embodiment, each of the haptics (3020) comprises an area (3030) configured to accept a pressure difference and translate it into a member of a group consisting of a force to move the lens, a torque to rotate the lens and any combination thereof.
In some embodiments, the area (3030) configured to accept a pressure difference can be mounted on or be part of other designs of IOL. The area (3030) configured to accept a pressure difference can be mounted on one or more haptics (3020), on the lens (3010) and any combination thereof.
In some embodiments, the pressure difference acts directly on the object to be moved or a portion thereof. In some variants of such embodiments, the object to be moved or the portion thereof additionally comprises an area configured to accept a pressure difference. In some variants of such embodiments, no additional pressure-accepting area is present.
Fig. 4 illustrates an exemplary IOL (4000) configured to be moved or rotated by a magnetic field. The IOL is of a standard type, comprising a lens (4010) and two haptics (4020). In this embodiment, each of the haptics (4020) comprises an area (4020) configured to react to a magnetic field and translate it into a member of a group consisting of a force to move the lens, a torque to rotate the lens and any combination thereof. The area (4020) configured to react to a magnetic field comprises a magnetizable material such as ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
In other embodiments, the area (4030) configured to accept a magnetic field can be mounted on or part of other designs of IOL. The area (4030) configured to accept a magnetic force can be mounted on one or more haptics (4020), on the lens (4010) and any combination thereof.
Fig. 5 schematically illustrates an IRS (5000) configured to be movable by either an acoustic manipulator or an electromagnetic manipulator. The IRS (5000) comprises two rings, primary intraocular ring (PIR) (5300) and a secondary device (SD) (5200). An exemplary haptic IOL (5100) is supported by the SD (5200). The exemplary IOL (5100) comprises a lens (5110) and two haptics (5120). The exemplary PIR (5300) comprises two tabs (5330), while the exemplary SD (5200) comprises three tabs (5230), two of them visible in the figure. For an electromagnetic manipulator, a tab will comprise magnetic material whereas, for an acoustic manipulator, a tab can be of any desired material and will typically be of the same material as the component to which it is attached.
For illustrative purposes, the tabs (5330) of the PIR (5300) are on an outward face of the PIR (5300), facing toward the exterior of the eye, while the tabs (5230) of the SD (5200) are at the back of the SD (5200) and face inward towards the center of IRS (5000). In other embodiments, the tabs can be at any position that does not interfere with the movement of the components of the IRS (5000).
In some embodiments of a PIR (5300) configured for use with an electromagnetic manipulator, at least a portion of the PIR (5300) comprises magnetic material and the PIR (5300) has no tabs. In some embodiments, the SD (5200) has no tabs. In such embodiments, for an acoustic manipulator, acoustic pressure on an IOL guide (5240) can move the SD (5200), while, for an electromagnetic manipulator, at least a portion of the SD (5200) comprises magnetic material.
In the example of Fig. 5, the IOL (5100) does not comprise tabs. For an acoustic manipulator, is can be moved directly by acoustic pressure, whereas, for an electromagnetic manipulator, at least a portion of the IOL (5100) comprises magnetic material. In other embodiments, as disclosed above, the IOL (5100) comprises at least one tab.
Fig. 6 schematically illustrates a glaucoma shunt (6000) with a movable shutter (6200) configured to reversibly cover at least a portion of a port (6100) of the shunt (6000). In this embodiment, the shutter (6200) comprises a cover (6210) and a tab (6220). The shutter (6200) can be moved by applying a pressure difference to the tab (6220) or, if the shutter (6200) comprises a magnetizable material, by applying a magnetic field to either the tab (6220) or the cover (6210). By sliding the shutter, the effective flow through the shunt (6000) can be changed according to the patient’s needs.
In some embodiments of the glaucoma shunt (6000), the shunt itself can be repositioned, either magnetically or acoustically, to improve its position in the eye. Movement of the shunt (6000) can be induced magnetically, acoustically and any combination thereof. Movement of the shutter (6200) can be induced magnetically, acoustically and any combination thereof. The means of inducing movement of the shunt (6000) need not be the same as the means of inducing movement of the shutter (6200).
In some embodiments of the ultrasonic manipulator, it can remove matter from a glaucoma shunt, for non-limiting example, by inducing the matter to move towards the end of the shunt furthest from the interior of the eye.
In some embodiments, a manipulator, either an acoustic manipulator or an electromagnetic manipulator, can alter at least one attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL. The attribute can be a material property of a nanoparticle, a position of a nanoparticle, and any combination thereof. By changing the attribute, behavior of the lens can be altered, for example, by changing the refractive index of at least a portion of the lens, by changing the degree of lens toricity, by changing the toric axis of the lens, and any combination thereof. By changing the refractive index of a portion of the lens, the amount of multifocality of the lens is altered.
The material property of the nanoparticle can be its refractive index, its shape and any combination thereof.
In some embodiments, a manipulator, either an acoustic manipulator or an electromagnetic manipulator, can change the rate of delivery of drug by at least partially opening or at least partially closing a shunt of a slow release drug delivery system. In preferred embodiments, the at least partially opening and the at least partially closing of the shunt are reversible.
In some embodiments, the acoustic manipulator is further configured to map a member of a group consisting of the shape of at least a portion of the eye, the size of at least a portion of the eye, the shape of at least a portion of an object in the eye, the size of at least a portion of an object in the eye and any combination thereof.
In some embodiments, the acoustic manipulator can map a member of a group selected from at least a portion of the interior of the eye, the location of at least a portion of an object in the interior of the eye and any combination thereof.
In some embodiments, the electromagnetic manipulator can, for objects comprising material responsive to an electromagnetic field, map the location of at least a portion of at least one such object in the interior of the eye.
EXAMPLE 1
An IRS can be rotated using radiation force, a nonlinear effect proportional to the acoustic wave amplitude, thus creating a continuous, non-oscillating force for a stimulus of a constant amplitude [Rudenko OV, Sarvazyan AP, Emelianov SY, (1996) Acoustic radiation force and streaming induced by focused nonlinear ultrasound in a dissipative medium. J Acoust Soc AM 99:2791- 2798. Doi: 10.1121/1.414805]. This nonlinear effect obtained implies the induction of a “constant” positive average pressure, induced by the wave along its propagation direction. When encountering a reflective surface, this radiation pressure induces radiation force [H. Azhari, Basics of biomedical ultrasound for engineers. 2010, Wiley: IEEE: Hoboken, N.J]. Thus, an object in the wave path that absorbs or reflects sound energy is subjected to a force, the acoustic radiation force, from the acoustic radiation.
Experimental setup and equipment For a proof-of-principle experiment, the ultrasound system can comprise a phased array integrated therapeutic-imaging transducer, a programmable ultrasound system, a function signal generator and an amplifier.
The integrated therapeutic-imaging transducer combined both a 64-element therapeutic phased array probe and a B-mode ultrasound imaging probe. The phased array transducer was constructed with piezoelectric elements.
The therapeutic probe elements were arranged in rings that were regularly arranged on the outer surface area of the integrated transducer. The radiation force needed to rotate the ocular implant was generated by the therapeutic probe.
The center frequency of the therapeutic probe elements was on the order of hundreds of kHz.
The imaging B-mode probe that was in the central circular hole of the spherical integrated transducer enabled the system to monitor the rotation of the implant, creating closed feed-back to the therapeutic probe. Unlike therapeutic transducers, imaging transducers’ center frequency is generally in order of few MHz such that a good resolution is obtained.
The programmable ultrasound system allowed control of both parts of the transducer independently and simultaneously. On one side, the therapeutic part of the transducer was dynamically focused through a focusing method known as “electronic focusing”, where, both the amplitude and the phase of the electrical signal that excited each element of the phased array are independently controlled by the ultrasound programmable system so that the delay of each element’s transmission is controllable. The control of the delay after each element is excited allowed the synthetically generation of a point of constructive interference of all the elements’ excitation signal and thus allowed steering of the focal point to any point in space. The delays are geometrically calculated using the following formula: (1)
Figure imgf000024_0001
where τi represents the delay of element i, xc, yc, zc are the coordinates of the furthest element from the focus point, xf, yf, zf are the coordinates of the focus point and xi, yi, zi are the coordinates of element i. it has to be noted that all these time values are calculated relative to a defined point on the aperture. On the other side, the programmable ultrasound system allows simultaneous control of the imaging part of the transducer in order to track the motion of the implant caused by the radiation force. Moreover, the ultrasound programmable system allows triggering of the function signal generator in order to excite each of the array’s elements.
The function signal generator, also called the waveform generator, generates different types of electrical waveforms over a large variety of frequencies and amplitudes. Some of the most common waveforms produced by the function generator are sine wave, square wave, triangular wave and sawtooth shapes. These waveforms can be either repetitive or single-shot and require either an internal or an external trigger source which, in this case, was given via the ultrasound programmable system.
Excitation parameters
In a preliminary experiment, the feasibility of moving a small piece of metal suspended in water by means of radiation pressure was checked using a 1 euro cent coin weighing 2.3 grams. For all of the tests, the excitation pulse transmitted by the function generator was composed of a pulse comprising 200 cycles of a 2.25MHz sine wave; different tests had different amplitudes. Motion of the coin first appeared when the amplitude was 20 mVpp (peak-to-peak) and it intensified with increasing amplitude, up to the maximum amplitude allowed by the amplifier, 120 mVpp. It is estimated that the force needed to rotate the ring is of the same order of magnitude as the force needed to move the euro cent. Since a radiation force of at least 20 mVpp was sufficient to move the euro cent, it is estimated that this will similarly be sufficient to rotate an intraocular implant.
The prototype of the intraocular implant is made of two concentric rings. In preferred embodiments, the inner ring has two arms extending from it to receive ultrasound pressure and initiate movement. The cross section of the surface on which the ultrasound is received is 1.25 mm X 0.8 mm. Moreover, the cross-sectional area of the focal point is defined by the full width at half maximum (FWHM) formula. Then, assuming a transducer with an outer diameter of 2 cm that is focused at depth of 1 cm, the frequency that should be used is in the range of 500 kHz-1.5 MHz so that it will match approximately the size of the arms and will concentrate the energy on the arms. Ultrasound safety indexes
Because the eye is vulnerable to thermal and mechanical damage from excessive ultrasonic energy, the Food and Drug Administration (FDA) and World Federation for Ultrasound in Medicine and Biology have imposed strict thermal index (TI) and mechanical index (MI) limits for ocular applications. The MI is a safety indicator related to mechanical effects, such as cavitation, of the sequence transmission while the TI gives a rough estimate of the risks resulting from undesired thermal effects. The FDA and World Federation for Ultrasound in Medicine and Biology TI limit is TI <1.0 and the MI limit is MI <0.23. [Food and Drug Administration, Guidance for Industry and FDA Staff Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers. Silver Springs; Maryland: Sep 9, 2008 and Palte HD, Gayer S, Arrieta E, et al., Are ultrasound-guided ophthalmic blocks injurious to the eye ? A comparative rabbit model study of two ultrasound devices evaluating intraorbital thermal and structural changes. Anesth Analg. 2012;115(1): 194-201. doi: 10.1213/ANE.0b013e318253622e].
Abbott [J. G. Abbott, Rationale and derivation of MI and TI—A review , Ultrasound Med. Biol., vol. 25, no. 3, pp. 431-441, Mar. 1999] has shown that the MI can be calculated by:
(2)
Figure imgf000026_0001
where PPNP is the peak negative pressure in MPa and fc is the center frequency in MHz and the TI of soft tissue can be calculated by:
(3)
Figure imgf000026_0002
where TIS is the thermal index of soft tissue, W01 is the maximum value of the time averaged acoustic output power emitted from any 1-cm length of the radiating aperture in the scan direction in mW, and fc is the center frequency in MHz.
Accordingly, the voltage and the frequency of the excitation for each array’s element will be chosen such that it allows motion of the implant while respecting the safety limitations of ocular applications as determined by the FDA.
In order to compute the thermal index, three different ultrasound sequence modes need to be considered - (a) without focusing when in non-scanning mode and, when in a scanning mode, either focused or steered, so that it can be assumed that most of the energy field is near the transducer; (b) plane waves in non-scanning mode where it can be assumed that most of the energy field is near the transducer; and (c) a non-scanning mode with focusing, where it can be assumed that most of the energy field is at the focus. For the 1 euro cent case described above, the experiment was performed using a non-scanning and focused sequence so that mode (c) is the more appropriate. In this case, the cross section at the focal point has to be estimated, generally through the FWHM formula at the focus depth. If the cross section at the focal point is smaller than 1 cm2, then the power parameter W0 will represent the total output power from the ultrasound source. Otherwise, W0 will be calculated in the smaller cross-sectional area of 1 cm2 through the cumulative temporally averaged intensity, ISPTA.
For example, consider an annular phased array transducer with an outer diameter of 2 cm composed of 64 circular elements of 0.1 cm diameter, with output power of 1 W, center frequency of fc - 250 kHz that is focused at depth of 1 cm. In this case, the cross-sectional area at the focal depth will be circular and its area will be:
(4)
Figure imgf000027_0001
where dcs, the diameter of the cross section at the focal depth, calculated by the FWHM formula:
(5)
Figure imgf000027_0002
where c is the acoustic velocity in soft tissue, assumed to be z is the focal depth and dtrans
Figure imgf000027_0005
is the aperture width, in this case, the outer diameter of the phased array transducer.
According to the parameters of the sequence described hereinabove, the diameter of the cross section obtained at the focal depth is
(6)
Figure imgf000027_0003
Therefore, the cross-sectional area Sxy, needed in order to determine W0, is
(7)
Figure imgf000027_0004
Since the cross-sectional area is smaller than 1 cm2, W0 will be the total output power from the ultrasound source, W0 = 1 W. Using this value and the center frequency of the transducer, TIS is- (8)
Figure imgf000028_0001
Assuming that the PNP measured by a hydrophone at the focal depth is 50 kPa, we can also compute the MI value of the se
Figure imgf000028_0002
quence
(9)
Figure imgf000028_0003
Therefore, for the phased array and the excitation parameters in the example above, although the mechanical index MI is well below the FDA limit, the thermal index TI exceeds the FDA limit. The TI can be reduced by reducing the total power Wo, by reducing the central frequency fc, by pulsing the power sufficiently to allow cooling, and by any combination thereof.
The proof-of-concept experiment demonstrates that an object of over 50 times the weight of an implant can be controllably moved by shaped ultrasonic radiation, with an acceptable MI and a TI close to the safe limit, showing that safe, controllable movement of an implant within an eye is most probable.

Claims

CLAIMS:
1. An acoustic manipulator, comprising: a base configured to be placed over an eye; a plurality of acoustic transducers attached to the base and arranged in a predetermined pattern, said plurality of acoustic transducers configured to be positioned with emitting faces at least one predetermined distance from a surface of an eye; a processor in communication with said plurality of acoustic transducers, said processor comprising software configured, when activated, to control, for at least one of said transducers, a transducer acoustic wave property selected from a group consisting of a phase, a frequency, an intensity and any combination thereof, for each of said plurality of acoustic transducers, said transducer acoustic wave property is controllable independent of said transducer acoustic wave property of any other of said plurality of acoustic transducers; wherein an acoustic field of a determinable shape, variable with time in a determinable manner, can be generated within an eye, said acoustic field configured to alter at least one property of an item within the eye in a determinable manner.
2. The acoustic manipulator of claim 1, wherein said predetermined distance is zero.
3. The acoustic manipulator of claim 1, wherein said predetermined distance is a thickness of an eyelid.
4. The acoustic manipulator of claim 1, additionally comprising a contact material selected from a group consisting of a biocompatible membrane, a liquid, a gel and any combination thereof in contact with said plurality of acoustic transducers.
5. The acoustic manipulator of claim 4, wherein said predetermined distance is a thickness of said contact material.
6. The acoustic manipulator of claim 1, wherein said item is selected from a group consisting of an object within the eye, a portion of the eye, and fluid within the eye.
7. The acoustic manipulator of claim 6, wherein said object within the eye is selected from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a blockage and any combination thereof.
8. The acoustic manipulator of claim 1, wherein said object within the eye comprises at least one tab configured to be movable by a force exerted by an acoustic field.
9. The acoustic manipulator of claim 1 , wherein said alteration of said property is selected from a group consisting of linearly moving at least a portion of said item, rotating at least a portion of said item, heating at least a portion of said item, and any combination thereof.
10. The acoustic manipulator of claim 1, additionally configured to measure an eye property selected from a group consisting of a shape of at least a portion of the eye, a size of at least a portion of the eye, a shape of at least a portion of an object in the eye, a size of at least a portion of an object in the eye and any combination thereof.
11. The acoustic manipulator of claim 10, wherein said transducer acoustic wave property is at least partly dependent on said measured eye property.
12. The acoustic manipulator of claim 1 , additionally configured to map a member selected from a group consisting of at least a portion of an interior of the eye, a location of at least a portion of an object in the eye and any combination thereof.
13. The acoustic manipulator of claim 1 , additionally configured to change an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
14. The acoustic manipulator of claim 13, wherein said attribute is selected from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
15. The acoustic manipulator of claim 14, wherein said material property of the nanoparticle is selected from a group consisting of refractive index, shape and any combination thereof.
16. The acoustic manipulator of claim 1, additionally configured to perform an action selected from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
17. The acoustic manipulator of claim 1, wherein the maximum acoustic pressure generated by the transducers is less than 104 Pa.
18. The acoustic manipulator of claim 1, wherein the ultrasound frequency is in a range of 0.5 MHz to 10 MHz.
19. The acoustic manipulator of claim 1, wherein the ultrasound frequency is in a range of 0.8 MHz to 5 MHz.
20. The acoustic manipulator of claim 1, wherein the ultrasound intensity is in the range of 1 mW/cm2 to 150 mW/cm2.
21. The acoustic manipulator of claim 1, wherein the ultrasound intensity is in a range of 10 mW/cm2 to 100 mW/cm2.
22. The acoustic manipulator of claim 1, wherein the base has a shape conformable to the eye.
23. An electromagnetic manipulator, comprising: abase; a plurality of magnetic sources attached to the base and arranged in a predetermined pattern, said plurality of magnetic sources configured to be positioned at least one predetermined distance from said eye; a processor in communication with said plurality of magnetic sources, said processor comprising software configured, when activated, to control a magnetic field property selected from a group consisting of a polarity, a magnetic field intensity, a magnetic field direction and any combination thereof of at least two of said plurality of magnetic sources, for each of said at least two of said plurality of magnetic sources, said magnetic field property is controllable independent of said magnetic field property of any other of said at least two of said plurality of magnetic sources; wherein a magnetic field of a determinable shape, variable with time in a determinable manner, can be generated within an eye, said magnetic field configured to move an object comprising a magnetic material within the eye in a determinable manner.
24. The electromagnetic manipulator of claim 23, wherein said base has a shape conformable to the eye.
25. The electromagnetic manipulator of claim 23, wherein said base is configured to be placed over an eye.
26. The electromagnetic manipulator of claim 23, wherein said predetermined distance is zero.
27. The electromagnetic manipulator of claim 23, additionally comprising a biocompatible membrane in contact with said plurality of magnetic sources.
28. The electromagnetic manipulator of claim 27, wherein said predetermined distance is the thickness of said membrane.
29. The electromagnetic manipulator of claim 23, wherein said object within the eye is selected from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a remnant from a medical procedure, a fragment separated from an object in the eye and any combination thereof.
30. The electromagnetic manipulator of claim 23, wherein said object within the eye comprises at least one portion configured to be movable by a magnetic field.
31. The electromagnetic manipulator of claim 30, wherein each of said at least one portion configured to be movable by a magnetic field comprises a material selected from a group consisting of ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
32. The electromagnetic manipulator of claim 23, wherein said alteration of said property is selected from a group consisting of linearly moving at least a portion of said object, rotating at least a portion of said object, heating at least a portion of said object, and any combination thereof.
33. The electromagnetic manipulator of claim 23, wherein each of said plurality of magnetic sources is selected from a group consisting of an electromagnet, a permanent magnet and any combination thereof.
34. The electromagnetic manipulator of claim 23, additionally configured to map a location of at least a portion of at least one object in an interior of the eye.
35. The electromagnetic manipulator of claim 23, additionally configured to change an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
36. The electromagnetic manipulator of claim 35, wherein said attribute is selected from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
37. The electromagnetic manipulator of claim 36, wherein said material property of the nanoparticle is selected from a group consisting of refractive index, shape and any combination thereof.
38. The electromagnetic manipulator of claim 23, additionally configured to perform an action selected from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
39. The electromagnetic manipulator of claim 23, wherein the magnetic field is in a range of 500 gauss to 3000 gauss.
40. The electromagnetic manipulator of claim 23, wherein the magnetic field is in a range of 800 gauss to 1500 gauss.
41. The electromagnetic manipulator of claim 23, wherein the magnetic field is 1000 gauss.
42. A method of manipulating items within an eye, comprising steps of: providing an acoustic manipulator, comprising: a base configured to be placed over an eye; a plurality of acoustic transducers attached to the base and arranged in a predetermined pattern, said plurality of acoustic transducers configured to be positioned with emitting faces at at least one predetermined distance from a surface of an eye; a processor in communication with said plurality of acoustic transducers, said processor comprising software configured, when activated, to control, for at least one of said transducers, a transducer acoustic wave property selected from a group consisting of a phase, a frequency, an intensity and any combination thereof, for each of said plurality of acoustic transducers, said transducer acoustic wave property is controllable independent of said transducer acoustic wave property of any other of said plurality of acoustic transducers; positioning said acoustic manipulator on an eye; by means of said software, determining said phase and said intensity for each of said plurality of acoustic transducers, for each of said plurality of acoustic transducers, said phase and said intensity being either fixed in time or varying in time; activating each of said plurality of acoustic transducers according to said phase and said intensity; generating within the eye an acoustic field of a determinable shape, variable with time in a determinable manner; thereby altering at least one property of an item within the eye in a determinable manner.
43. The method of claim 42, additionally comprising a step of setting said predetermined distance to zero.
44. The method of claim 42, additionally comprising a step of setting said predetermined distance to a thickness of an eyelid.
45. The method of claim 42, additionally comprising a step of providing a contact material selected from a group consisting of biocompatible membrane, a liquid, a gel and any combination thereof in contact with said plurality of acoustic transducers.
46. The method of claim 45, additionally comprising a step of setting said predetermined distance to be a thickness of said contact material.
47. The method of claim 42, additionally comprising a step of selecting said item from a group consisting of an object within the eye, a portion of the eye, and fluid within the eye.
48. The method of claim 47, additionally comprising a step of selecting said object within the eye from a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a blockage and any combination thereof.
49. The method of claim 42, additionally comprising a step of providing said object within the eye comprising at least one tab, said tab configured to be movable by a force exerted by an acoustic field.
50. The method of claim 42, additionally comprising a step of selecting said alteration of said property from a group consisting of linearly moving at least a portion of said item, rotating at least a portion of said item, heating at least a portion of said item, and any combination thereof.
51. The method of claim 42, additionally comprising a step of measuring an eye property selected from a group consisting of a shape of at least a portion of the eye, a size of at least a portion of the eye, a shape of at least a portion of an object in the eye, a size of at least a portion of an object in the eye and any combination thereof.
52. The method of claim 51, wherein said transducer acoustic wave property is at least partly dependent on said measured eye property.
53. The method of claim 42, additionally comprising a step of mapping a member of a group selected from at least a portion of an interior of the eye, a location of at least a portion of an object in the eye and any combination thereof.
54. The method of claim 42, additionally comprising a step of changing an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
55. The method of claim 54, additionally comprising a step of selecting said attribute from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
56. The method of claim 55, additionally comprising a step of selecting said material property of the nanoparticle from a group consisting of refractive index, shape and any combination thereof.
57. The method of claim 42, additionally comprising a step of selecting an action from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
58. The method of claim 42, additionally comprising a step of selecting the maximum acoustic pressure generated by the transducers to be less than 104 Pa.
59. The method of claim 42, additionally comprising a step of selecting the ultrasound frequency to be in a range of 0.5 MHz to 10 MHz.
60. The method of claim 42, additionally comprising a step of selecting the ultrasound frequency to be in a range of 0.8 MHz to 5 MHz
61. The method of claim 42, additionally comprising a step of selecting the ultrasound intensity to be in the range of 1 mW/cm2 to 150 mW/cm2.
62. The method of claim 42, additionally comprising a step of selecting the ultrasound intensity to be in a range of 10 mW/cm2 to 100 mW/cm2.
63. The method of claim 42, additionally comprising a step of providing the base having a shape conformable to the eye.
64. A method of manipulating items within an eye, comprising steps of: providing a magnetic manipulator, comprising: abase; a plurality of magnetic sources attached to the base and arranged in a predetermined pattern, said plurality of magnetic sources configured to be positioned at at least one predetermined distance from said eye; a processor in communication with said plurality of magnetic sources, said processor comprising software configured, when activated, to control a magnetic field property selected from a group consisting of a polarity, a magnetic field intensity, a magnetic field direction and any combination thereof of at least two of said plurality of magnetic sources, for each of said at least two of said plurality of magnetic sources, said magnetic field property is controllable independent of said magnetic field property of any other of said at least two of said plurality of magnetic sources; positioning said magnetic manipulator at said at least one predetermined distance from said eye; by means of said software, determining said magnetic field property for each of said plurality of magnetic transducers, for each of said plurality of magnetic transducers, said magnetic field property being either fixed in time or varying in time; activating each of said plurality of magnetic transducers according to said determined magnetic field property; generating within the eye a magnetic field of a determinable shape, variable with time in a determinable manner; thereby moving within the eye in a determinable manner an object comprising a magnetic material.
65. The method of claim 64, additionally comprising a step of providing said base conformable to a shape of said eye.
66. The method of claim 64, additionally comprising a step of placing said base over said eye.
67. The method of claim 64, additionally comprising a step of setting said predetermined distance to zero.
68. The method of claim 64, additionally comprising a step of providing a biocompatible membrane in contact with said plurality of magnetic sources.
69. The method of claim 68, additionally comprising a step of setting said predetermined distance to be the thickness of said membrane.
70. The method of claim 64, additionally comprising a step of selecting said object within the eye is a group consisting of at least a portion of an intraocular lens, at least a portion of an intraocular ring system, at least a portion of a glaucoma shunt, at least a portion of an implantable miniature telescope for macular degeneration, a retinal chip, a sensor, a remnant from a medical procedure, a fragment separated from an object in the eye and any combination thereof.
71. The method of claim 64, additionally comprising a step of providing said object within the eye comprising at least one portion configured to be movable by a magnetic field.
72. The method of claim 71, additionally comprising a step of selecting each of said at least one portion configured to be movable by a magnetic field comprising a material from a group consisting of ferrous material, ferromagnetic material, diamagnetic material, a permanent magnet, an electromagnet and any combination thereof.
73. The method of claim 72, additionally comprising a step of selecting said alteration of said property from a group consisting of linearly moving at least a portion of said object, rotating at least a portion of said object, heating at least a portion of said object, and any combination thereof.
74. The method of claim 64, additionally comprising a step of selecting each of said plurality of magnetic sources from a group consisting of an electromagnet, a permanent magnet and any combination thereof.
75. The method of claim 64, additionally comprising a step of mapping a location of at least a portion of at least one object in an interior of the eye.
76. The method of claim 64, additionally comprising a step of changing an attribute of at least one nanoparticle in an arrangement of nanoparticles within an IOL.
77. The method of claim 64, additionally comprising a step of selecting said attribute from a group consisting of a material property of the nanoparticle, a position of the nanoparticle, and any combination thereof.
78. The method of claim 77, additionally comprising a step of selecting said material property of the nanoparticle from a group consisting of refractive index, shape and any combination thereof.
79. The method of claim 64, additionally comprising a step of selecting an action from a group consisting of at least partially opening, at least partially closing and any combination thereof a shunt of a slow release drug delivery system.
80. The method of claim 64, additionally comprising a step of selecting the magnetic field to be in a range of 500 gauss to 3000 gauss.
81. The method of claim 64, additionally comprising a step of selecting the magnetic field to be in a range of 800 gauss to 1500 gauss.
82. The method of claim 64, additionally comprising a step of selecting the magnetic field to be 1000 Gauss.
PCT/IL2021/050798 2020-06-29 2021-06-29 Intraocular manipulation device WO2022003682A1 (en)

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