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    • 专利摘要:

    公开号:BE1020907A3
    申请号:E201200276
    申请日:2012-04-26
    公开日:2014-09-02
    发明作者:Andrew Marshal；Max Maginness；Michel Alvarez
    申请人:Istar Medical；
    IPC主号:
    专利说明:

    "Improvements in or relating to the management and treatment of glaucoma"
    The present invention relates to improvements in or related to the management and treatment of glaucoma and more particularly to glaucoma devices that incorporate intraocular pressure sensors and glaucoma drainage devices.
    The mammalian eye includes an anterior chamber located between the cornea and the iris and the lens. This chamber is filled with a fluid known as aqueous humor. A trabecular system, comprising a plurality of microscopic passages, is located in the angle between the iris and the cornea. In the normal human eye, the aqueous humor is generated at a constant rate, typically about 2.7 microliters per minute (pl / min) by the ciliary body behind the iris. The aqueous humor flows between the crystalline lens and the iris and then exits through the trabecular meshwork and is brought back into the circulatory system.
    The intraocular pressure (IOP) maintaining this flow in the normal eye tends to remain in a range of 10 mmHg to 20 mmHg. However, there may be significant changes in IOP related to the cardiac cycle, the daytime blinking and other causes. This makes it difficult to obtain representative IOP values from occasional measurements. In the most common chronic form of glaucoma where the irido-comedic angle remains open, there is a blockage of the exit path of the trabecular system which causes an accumulation of excess fluid in the eye and consequently causes the IOP to rise at a value consistently higher than about 18 mm Hg. In some cases, IOP can be up to 50 mm Hg or more. Over time, this increase in pressure results in irreversible damage to the optic nerve and loss of vision.
    Glaucoma is a leading cause of blindness in the world and affects more than 60 million people. Glaucoma is associated with many conditions including high blood pressure, diabetes, steroid use and ethnic origins. Various treatments are currently available for glaucoma including dosing regimens, laser trabeculoplasty, trabeculotomy and trabeculectomy and intraocular drainage implants.
    Drugs are frequently administered as ophthalmic drops to control fluid influx, i.e., aqueous humor formation, or to open the trabecular system. Erratic dosages, side effects and poor patient compliance are common problems.
    In an alternative to using. For the treatment of glaucoma, surgical creation of bypass channels or drains around and through the blockage of the trabecular system is adopted as a means of removing excess fluid and thus the rise of IOP. In trabeculoplasty, a laser is used to create small openings in the trabecular eye system so that the aqueous humor can be drained through the trabecular system to reduce intraocular pressure in the anterior chamber of the eye. This method of treatment is mainly used for open-angle glaucoma.
    Surgical techniques include trabeculotomy and trabeculectomy. Trabeculotomy is a surgical technique in which an opening is created in the trabecular system using a small instrument to allow fluid to flow from the anterior chamber. Trabeculectomy is the most common surgical technique for glaucoma, in which part of the trabecular system is removed. These methods allow the fluid to accumulate under the conjunctiva and be reabsorbed by the eye.
    Implanted devices are most often used when other methods of treatment have become ineffective but have been proposed, more recently, as first choice, alone or at the same time as a drug therapy. These implants include drainage devices that are inserted into the eye so that the aqueous humor can be drained through a drainage path and exit the anterior chamber. In the most commonly used implants, eg Molteno implants and Baerveldt shunts, a drainage channel is formed by means of a placed tube. between the anterior chamber and a fluid dispersion plate generally located supra-scleral, below the conjunctiva. The fluid dispersed from the plate forms a puddle or "bubble" (bleb) which is gradually re-absorbed by the outer layers of the eye.
    However, the drainage plates of these devices can often be large and rigid, causing fibrotic reactions with the surrounding tissue that can progressively reduce the effectiveness. For example, plates can have areas of 425 mm2 in size and cover almost 25% of the eye area. Although the dispersion plates may be curved to match the general shape of the outer layers of the eye, they can only approach the actual shape of the eye of an individual patient. A lack of concordance of the plate with the geometry of the sclera can cause chronic microtraumas problems. Although the newer drainage devices are smaller in size, they are still rigid with the ability to cause trauma during insertion and subsequent use.
    To overcome some of these weaknesses, US-A-6102045 discloses a compact, flexible, fibrotic-reduced implant that lowers intraocular pressure (IOP) in the eye. The implant, comprising a porous cellulosic membrane, extends into the anterior chamber of the eye, then through an opening in the limbus to a drainage zone under a scleral flap, and preferably located between the sclera and the choroid. . Once implanted, the fluid is absorbed from the drainage zone into the choroidal vascular bed, allowing the aqueous humor to drain from the anterior chamber. Such flexible devices, providing a function of drain or wick, are often called sétons.
    In the detection and monitoring of glaucoma, routine ophthalmic examinations on an annual or other basis commonly include a measure of IOP. But, this low measurement frequency may not detect increased pressure in good time. In addition, a single measure gives no indication of potentially damaging variations from day to day. The established "ideal" tonometry instruments require medical skill and are suitable only for occasional use.
    Several devices have been disclosed to measure IOP more frequently. In particular, some of these utilize a pressure sensor surgically implanted within the eye and combined with external wireless, magnetic, optical or other means to interrogate the implant and obtain IOP readings.
    It is very common to deploy passive sensors, that is, sensors that do not need an internal power source, to avoid battery chemicals in the eye. The interrogation methods then provide an externally applied form of energy to activate the implant when a survey is to be performed. The techniques often resemble those well understood in the field of radio frequency identification (RFID).
    But, these sensors have the common limitation of specifically requiring surgery to implant them. In many cases, there may not be a medical risk-benefit rationale for a surgical procedure. Therefore, IOP sensors combined with other ophthalmic devices, most commonly intraocular lenses (IOLs), are used to avoid the need for additional surgery.
    Many known IOP sensors are relatively large in the context of the dimensions of the eye and are necessarily rigid to achieve proper sensor and read operation. There is a risk of blocking the optical path and trauma. IOP sensors are described in US-B-7677107, US-B-6939299, US-B-6579235, US-A-2009/0299216 and US-A-2009/0069648.
    US-B-7677107 discloses a wireless pressure sensor which includes an inductor-capacitor arrangement sandwiched between protective layers of impermeable polymeric materials. The portion of a first substrate is configured to form a cavity with a first capacitor plate, an inductor also being formed on the first substrate. A second substrate having a second capacitor plate formed thereon is attached to the first substrate and seals the cavity formed in the first substrate, the second substrate being movable relative to the first substrate. Pressure changes are detected by corresponding capacitance changes resulting in changes in the resonant frequency of the combination. The inductive element is necessarily held rigid to maintain a stable value and can not be in accordance with the anatomy of the individual patient.
    US-B-6939299 discloses a micro-machined chip on which an inductor-capacitor assembly is mounted. The capacitor includes an upper plate and a lower plate that are prepositioned during manufacture. Fluid pressure changes in the eye cause plate deflections and hence capacitance changes, detectable as a change in resonance frequency similarly to US-B-7677107.
    US-B-6579235 discloses a passive intraocular pressure sensor which operates with a tracking recorder which is worn by the patient in whose eye the sensor is implanted. Magnetic coupling provides a link between the sensor and the tracking device.
    US-A-2009/0299216 discloses an intraocular pressure sensor which utilizes a capacitor and a reference chamber to perform pressure comparisons within the eye. The reference chamber has a predetermined acceptable pressure that is compared with the sensed pressure to provide an indication of pressure exiting within the eye.
    US-A-2009/0069648 discloses an electromechanical microsystem device (MEMS) which uses piezoresistive elements to sense pressure changes.
    An intraocular pressure sensor is also described in an article entitled "Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant" by Po-Jui Chen, Saloomeh Saati, Rohit Varma, Mark S. Humayun and Yu-Chong Tai, Journal of Microelectromechanical Systems, Vol. 19, -No. August 4, 2010. In this article, passive wireless detection is described as using an implanted wireless pressure sensor comprising an LC circuit having a resonant frequency varying under pressure. The sensor comprises a flexible coil substrate that can be bent for implantation and deployed once implanted, taking a rigid shape. Inductive coupling is used for a wireless link between the implanted sensor and an external device.
    When glaucoma has progressed to a point where a drainage device has become medically indicated, the need and benefit of continuous IOP monitoring is self-evident. It is therefore advantageous to combine the insertion of a glaucoma drainage device with a pressure sensor. This only requires a surgical procedure to insert both devices and provides a glaucoma management system that can be easily monitored.
    Such a combination is described in US-B-7678065. In the latter, an IOP sensor is implanted together with a drainage device. However, the sensor is not an integral part of the drainage device and must, after insertion, be fixed separately inside the eye, making the complexity comparable to two separate procedures.
    An article entitled "Design of a Wireless Intraocular Pressure Monitoring System for a Glaucoma Drainage Implant" by Kakaday T, Plunkett M, Mclnness S, Li JS, Voelker NH, Craig JE, Proc ICEMR 23, pages 198-201, 2009, describes a PIO sensor implant that is attached to the outer plate of a Molteno glaucoma drainage device. The PIO sensor consists of a MEMS capacitive pressure sensor and a planar inductor printed directly on a flexible, biocompatible, polyimide printed circuit board (PCB) to complement a parallel resonance circuit, the circuit frequency varying with the pressure and being detectable on the outside. The sensor implant is encapsulated in a biomaterial, polydimethylsiloxane (PDMS - commonly known as silicone rubber), to protect it from the aqueous environment. The PIÖ sensor is based on maintaining the plate with a generally fixed shape with predictable deflection under the pressure of fluid entering the plate through the tube from the anterior chamber. Disadvantages of such an implant include the increased thickness of the drainage plate which can exacerbate the blistering effects due to the formation of a bleb (filtration bubble), and the measurement is that of the pressure in the blister plate. drainage rather than a direct measure of the pressure in the anterior chamber.
    Although IOP sensors and drainage devices are known as discussed above, these devices are distinct and tend to be located in different parts of the eye because of their different functions.
    Therefore, an object of the present invention is to provide an integrated intraocular pressure sensor and glaucoma drain device which requires only one surgical procedure for implantation, is comfortable for the anatomy of the eye and which is located in the eye at a place that is suitable for measuring pressure and allowing drainage.
    According to a first aspect of the present invention, there is provided an integrated intraocular device comprising: an intraocular pressure sensor element; an antenna element; and an aqueous humor drainage element; characterized in that the drainage element comprises a highly flexible porous biocompatible material including the intraocular pressure sensing element and the antenna element.
    The drainage element comprises a body portion housing the antenna element and a base plate portion housing the intraocular pressure sensor element. The body portion and the base plate portion are connected to each other by means of a smaller neck section portion which is placed through a limbal incision during surgery to position the drainage device.
    In one embodiment, the body portion is substantially circular and the antenna element comprises a circular spiral located within the circular body portion. In another embodiment, the body portion is substantially rectangular and the antenna element comprises a rectangular spiral located within the rectangular body portion. In each case, the antenna element may be disposed substantially around the periphery of the body portion.
    The antenna element and the intraocular pressure sensor element are preferably connected by wires passing between the body portion and the base plate portion. At least one protective layer may be located between the intraocular pressure sensing element, the antenna element, the wires and the porous biocompatible material, the porous biocompatible material including each protective layer.
    A single protective layer is preferably formed around the intraocular pressure sensing element, the antenna element and the wires, the single protective layer having an opening proximate to the intraocular pressure sensing element to allow pressure aqueous humor to be measured through the porous biocompatible material.
    The porous biocompatible material may comprise a natural polymer or a synthetic polymer. In a preferred embodiment of the present invention, the synthetic polymer is silicone rubber.
    The average thickness of the porous biocompatible material is between 100 μm and 1000 μm, preferably between 100 μm and 500 μm, more preferably between 200 μm and 500 μm.
    The porous biocompatible material comprises substantially spherical open pores having an average pore diameter of from 20 μm to 90 μm, preferably from 25 μm to 70 μm, and more preferably from 25 μm to 30 μm. In the integrated intraocular device of the present invention, the preferred range is between about 25 pm and 30 pm.
    The substantially spherical open pores may have pore interconnections of between 15% and 40% of the average pore diameter. Most often, there will be between 4 and 7 interconnections between any pore and its neighbors.
    In one embodiment, the porous biocompatible material comprises an irregular outer surface having a topography of "ridges and valleys". The surface variations of the irregular outer surface may range from 100 μm to 300 μm based on the average thickness of the porous biocompatible material. By having this topography of "peaks and valleys" in contact with the ocular tissue when the device is implanted in the eye, the fibrotic reactions to the implanted device can be further reduced.
    The porous biocompatible material provides a drain for aqueous humor flow with a resistance preferably not exceeding a pressure drop of 1 mm Hg for a flow of 1 μl / min.
    It is preferred that the antenna element consists of an inductive antenna element. The antenna element can be flexible and this has the advantage that the device can easily conform to the contours of the eye after implantation, thereby reducing the trauma to a minimum.
    The antenna element and the intraocular pressure sensor element are preferably both passive.
    The integrated intraocular device of the present invention comprises an intraocular pressure sensor processing system, the intraocular pressure sensor itself being part of said system. The intraocular pressure sensor processing system includes a decoder for decoding interrogation signals received by the antenna element and a detector for obtaining power signals from these received signals. The treatment system also includes a power storage module for the operating power supply. In addition, said system also includes an encoder for encoding the pressure reading signals to be transmitted by the antenna element.
    According to another aspect of the present invention, there is provided an intraocular pressure monitoring system comprising: - an interrogation and extracorporeal treatment system; an integrated intraocular device implanted as described above, the intraocular device being arranged to communicate wirelessly with the interrogation and processing system.
    The interrogation and processing system preferably comprises a transceiver element for transmitting activation signals to the integrated intraocular device and for receiving signals corresponding to intraocular pressure measurements taken by the integrated intraocular device when it is activated. The interrogation and processing system may include a communication module for transmitting intraocular pressure measurement data to a remote location. The interrogation and treatment system can be mounted in at least one of a pair of spectacles, a wall, a pillowcase or a sheet, the pillowcase or the sheet being appropriate to receive measurements when the patient is sleeping.
    It should be known that the interrogation and processing system can be divided into component parts so that the transceiver can be located in a sheet that can be positioned under a pillow (or the pillowcase itself), transceiver being connected to the rest of the interrogation and processing system by a cable. This means that the transceiver can be removed from the sheet when it needs to be washed without damaging the system.
    According to another aspect of the present invention, there is provided a method of monitoring intraocular pressure, the method comprising the steps of: -implanting an integrated intraocular device as described above; and (b) determining intraocular pressure measurements using the intraocular pressure sensing element in the integrated intraocular device; characterized in that step a) comprises implanting the portion of the device comprising the intraocular pressure sensor element within the anterior chamber of the eye.
    Step a) comprises the steps of making a limbal incision in the eye; placing the baseplate portion within the anterior chamber of the eye, the neck portion being located in the limbal incision; and position the body part inside the outer layers of the eye. In addition, step a) further comprises placing the body portion between the choroid and sclera of the eye.
    Step b) comprises the use of an extracorporeal device for interfacing with the intraocular pressure sensor element to provide an output of intraocular pressure measurements.
    The present invention includes a glaucoma treatment system comprising a glaucoma drain device formed from an anatomically conformable porous biomaterial suton surgically implanted to form a fluid conducting path between the anterior chamber of the eye and the sclera, seton comprising means for measuring intraocular pressure and other physiological conditions. Wireless reading of these measurements is provided using an external interrogation device adapted to provide energy to the implant and to obtain wireless readings of physiological measurements.
    In this way, a fully integrated and compact drain and sensor device can be implanted as a single device in a single procedure. In addition, the sensor element can be positioned correctly to measure the IOP directly in the anterior chamber while the drain extends from the anterior chamber to a sub-scleral region of the eye. Alternatively, if the drainage device has a low flow resistance, i.e. less than about 1 mm Hg pressure drop at a flow rate up to the natural flow rate in the eye , that is to say between about 1 and 3 μΙ / min, the pressure sensor element can be located in the diffusion zone. Such alternative placement will depend on the low resistance to flow through the device and the ability of the fluid to diffuse in any direction within, and hence around, the drainage body. The porous biomaterial from which the integrated device of the present invention is made provides channels for the fluid through its structure that are substantially the same in any direction. This provides an important condition for a pressure measurement at any location to accurately represent the pressure of the largest ocular volume.
    In addition, the porous biomaterial structure controls fibrosis so that low resistance flow pathways are maintained through the material and changes in pressure sensitivity over time are reduced to a minimum.
    In addition, a device that is highly flexible is provided, this device allowing self-adaptation to the eye contour of each individual patient in which the device is implanted.
    In addition to the measurement of pressure, additional sensors may be provided to measure other physiological conditions, for example temperature, aqueous humor salinity, glucose concentration, drug concentration applied topically to the eye.
    For a better understanding of the present invention, reference will now be made, by way of example only, to the accompanying drawings in which:
    Figure 1 illustrates a sagittal sectional view of an eye;
    Figure 2 illustrates an enlarged cross-sectional view of the eye showing portions of the anterior chamber and outer layers of the eye;
    Figure 3 illustrates a perspective view of the eye showing a preferred positioning of the device according to the present invention;
    Figures 4 and 5 respectively illustrate plan views of the first and second embodiments of an integrated PIO and drain sensor device according to the present invention; Figure 6 illustrates a cross-section through the base plate portion of the device shown in Figure 5;
    Figure 7 illustrates a cross-section through the body portion of the device as shown in Figure 5;
    Figure 8 illustrates a longitudinal section through the device of Figure 5; and Figure 9 illustrates a block diagram of a processing system for use with the device as shown in Figures 4 to 8 above.
    The present invention will be described in connection with particular embodiments and with reference to certain drawings but the invention is however not limited thereto. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn to scale for illustrative purposes.
    In accordance with the present invention, an integrated IOP sensor and glaucoma drainage device that includes an IOP sensor element and an inductive antenna element is provided. The PIO sensor element and the antenna element are sandwiched between at least two layers of a biocompatible open-pore material. The biocompatible material has two functions, namely to protect the sensor element and the antenna from fibrotic encapsulation and to form the drainage device. When the device is implanted, the open-pore biocompatible structure further allows aqueous humor to be communicated with the PIO sensor element within the integrated device.
    A suitable biocompatible material structure is described in WO-A-2005/032418. The described biocompatible material is porous and comprises a biocompatible polymer scaffold which defines a matrix of interconnected pores having similar diameters. The term "similar diameters" means that the difference in diameter between two pores is less than 20% of the larger diameter. Typically, the average pore diameter is from about 20 μm to about 90 μm, preferably from about 20 μm to about 40 μm. For use in the integrated device of the present invention, the preferred range is from about 25 μm to about 30 μm.
    Each pore is connected to at least 4 other pores by bonds representing between about 15% and about 40% of the average pore diameter. In some embodiments, each pore is connected to between about 4 and 12 other pores, for example between about 4 to 7 other pores. At least 90% of the pores are connected in this way, preferably at least 95% and more preferably at least 97%.
    The porous biocompatible material may have a thickness of from about 100 μm to about 1000 μm, for example from about 100 μm to about 500 μm. For the present drain device, the thickness of the biocompatible material is chosen depending on the desired aqueous humor flow and the strength requirements. Most often, the total thickness of the porous section will be between about 200 μm and about 500 μm. This can be achieved by additionally combining the respective thicknesses of multiple layers as in the sandwich construction to which reference has been made previously.
    The porous biocompatible scaffold material may comprise any biocompatible polymer such as synthetic polymers, naturally occurring polymers, or mixtures thereof. Exemplary synthetic biocompatible polymers include, but are not limited to, poly (2-hydroxyethyl methacrylate), silicone rubber, poly (ε-caprolactone) dimethyl acrylate, polysulfone, poly (methyl methacrylate) (PMMA), fluoropolymers (such as Teflon), polyethylene tetraphthalate (PET or Dacron), polyamide (such as nylon), polyvinyl alcohol, polyurethane, interpenetrating network polymers, and mixtures thereof. Exemplary natural biocompatible polymers include, but are not limited to, fibrous or globular proteins, complex carbohydrates, glycosaminoglycans or mixtures thereof. Thus the polymeric scaffold can comprise collages of all types, elastin, hyaluronic acid, alginic acid, desmin, versican, matricellular proteins such as SPARC (osteonectin), osteopontin, thrombospondin 1 and 2, fibrin, fibronectin, vitronectin, albumin, etc. Natural polymers can be used as a scaffold or as an additive to improve the biocompatibility of a synthetic polymer.
    The scaffold of porous biocompatible material may be a hydrogel, for example a degradable hydrogel, which is formed by reacting a low molecular weight poly (s-caprolactone) diol with an excess of methacryloyl chloride to give a polyester compound with Methacrylate end groups, the polyester compound being copolymerized with 2-hydroxyethyl methacrylate (HEMA) to provide a crosslinked hydrogel with hydrolyzable linkages.
    The polymer scaffold generally has a low degree of microporosity. The term "microporosity" is a measure of the presence of small micropores in the polymer scaffold itself (as opposed to the pores defined by the scaffold). In some embodiments, all or substantially all of the micropores in the polymer scaffold are from about 0.1 μm to about 5 μm, for example, from about 0.1 μm to about 3 μm, or from about 0.1 μm to about 2 pm. The term "low degree of microporosity" means that the micropores represent less than 2% of the volume of the polymeric scaffold, as measured by measuring the percentage of void space in a cross section through the polymeric scaffold.
    Biologically active molecules can be introduced into the porous biomaterial by forming the porous biomaterial in the presence of the biologically active molecules, allowing the biologically active molecules to diffuse into a porous biomaterial or by otherwise introducing the biologically active molecules into the biomaterial. porous biomaterial.
    The biocompatible material may be formed from a template comprising a porogen matrix, that is, any structure that can be used to create a template and that is removable once the biocompatible polymer scaffold is formed in conditions that do not destroy the polymer scaffold. For example, PMMA or polystyrene beads can be used.
    The pores and porogens may have any suitable form, for example spherical, dodecahedron, pentagonal dodecahedron and ellipsoid. The pores and porogens have a rotundity of at least 0.1, for example at least about 0.3 or at least about
    6V
    0.7. The term "rotundity" being defined as where V is nD3 volume and D is the diameter of pores and porogens. As an indication, a sphere has a rotundity of 1.0.
    The porous biocompatible material disclosed in WO-A-2005/032418 is constructed by forming a substantially spherical monodisperse porogenous template, forming the porous biomaterial around the template and then removing the template to produce the porous biocompatible material.
    The template can be formed by compacting the porogens in a mold using ultrasonic agitation or any other suitable method to obtain a tightly compacted porogen matrix. Porogens can be sintered fused when the sintering time and / or the sintering temperature can be used to increase the size and growth rate of the bonds. Other methods can be used to fuse porogens, for example by partially dissolving them by treatment with a suitable solvent.
    Once the jig is created, the biocompatible polymer scaffold is formed around the jig. The polymer scaffold can be formed by polymerizing a mixture of polymer precursors, including suitable polymer precursors and crosslinking reagents, around the template. The impregnation of the template with the precursor mixture can be obtained by applying one or more means depending on the viscosity of the mixture including: capillary wick, gravity, vacuum, pressure or centrifugation.
    After the biocompatible polymer has been formed, the template is removed by solvent extraction to produce the porous biomaterial. If PMMA beads are used as porogens, they can be extracted by multiple immersions in a dichloromethane solution or a 9: 1 v / v acetone-water solution. Solvent selection is performed for compatibility with the final porous material.
    In a method of constructing porous polymeric scaffold sheets, a mixture of polymer precursors was formed on a template comprising sintered PMMA beads. The beads were added to the molds comprising two outer layers of solid PMMA about 0.12 mm thick, separated by Teflon spacers of the desired final thickness of the sheet and further strengthened by sandwiching them between microscope slides tight. The beads were compacted using ultrasonic agitation and sintered for 18.5 hours at 190 ° C to give neck sizes of about 30% of the bead diameter. After sintering, the microscope slides were removed and the resulting PMMA template was infiltrated with the MED-6215 silicone polymer precursor mixture produced by Nusil Technologies LLC, freshly mixed in a weight ratio of 10: 1 as specified by the manufacturer. The templates were placed in centrifuge tubes and covered with untreated liquid silicone. Centrifugation was then performed at about 24,000 g for 1.5 hours to ensure full penetration of the template by the untreated silicone. After removing the centrifuge, the silicone impregnated templates were placed in an oven at 75 ° C for 16 hours to complete the silicone treatment. Finally, the PMMA template was removed by stirring in dichloromethane (DCM) solvent and then purified using fresh DCM in a Soxhlet extraction apparatus.
    For the porous silicone material, an analysis of the untreated residual components present after the above process showed less than 0.1%, well below the manufacturer's 1% specification for long-term medical implantation.
    In an alternative method, the porous biomaterial is formed from poly (2-hydroxyethyl methacrylate) hydrogel (polyHEMA). To prepare it, the precursor components listed in Table 1 were used in the indicated volume ratios.
    Table 1.
    The mixture was fed under a pressure of about 2 atmospheres into a template of PMMA beads prepared as above, allowed to polymerize for 24 hours and the PMMA was then extracted with a 9: 1 v / v solution. acetone-water to give porous hydrogel sheets of polyHEMA doped with type I collagen. '
    Before assembling the templates, the monodispersity of each size of the PMMA beads was examined by light microscopy. For each ball size, at least 95% of the beads had a diameter equal to the average ball diameter of +/- 20%.
    The monodispersity of the necks in the pore-forming templates was measured from images obtained by SEM (scanning electron microscopy). For each ball size, it was found that at least 95% of the passes were between 25% and 35% of the average ball diameter. SEM has also been used to determine the structure of porous biomaterials. Examination of the SEM images revealed that each pore was connected to between 4 and 7 adjacent pores and the porous materials had a precisely uniform pore structure.
    For any of the materials, specific device shapes may be prepared from the sheets prepared as above using formed punches or other suitable cutting means.
    Referring first to Figures 1 and 2, a sagittal section through an eye 100 is shown illustrating the position of the cornea 110, the iris 120, the pupil 130, the lens 140, the ciliary body 150 (shown in FIG. clearly in Figure 2). The anterior chamber 160 is located between the crystalline lens 140 and the cornea 110.
    In the normal eye, the aqueous humor comes from the ciliary body 150 and flows between the iris 120 and the crystalline lens 140 in the anterior chamber 160 and then exits through the porous trabecular system 170 located in the angle between the iris 120 and cornea 110 as indicated by arrow 180. Sclera 190 and choroid 195 are also shown.
    In the glaucomatous eye, the trabecular meshwork 170 is commonly blocked, causing a damaging increase in the pressure inside the eye. An integrated PIO sensor and drain device 200 according to the present invention can be implanted to form a fluid path from the anterior chamber 160 to a sub-scleral zone 210, bypassing the blockage and restoring the fluid flow as indicated by the arrow 180. With the drainage device thus positioned, the PIO sensor element (not shown) is located in such a way that the pressure in the anterior chamber 160 can be detected, and the antenna element (also not shown) is in this sub-scleral zone 210. In this position, the pressure data relating to the anterior chamber 160 may be detected by a remote device (not shown) which is coupled to the antenna element. This will be described in more detail below.
    Figure 3 shows a preferred supra-temporal location for the integrated PIO sensor and drainage device 200 according to the present invention. For a left eye, the device 200 is in a position between about "1 hour" and about "2 hours". Similarly, for the right eye, the device 200 is in a position between about "10 hours" and about "11 hours". This offers an anatomical advantage in that right muscles 196 are avoided during surgery and the technical advantage of favorable positioning for wireless communication with an external interrogator as will be described in more detail below. . In addition, the vision is not hindered by the location of the device 200 inside the eye.
    The integrated IOP sensor and drainage device 200 as described with reference to FIGS. 1 to 3 will be further described. detailed in Figures 4 to 8 below. Without limitation, the descriptions refer to devices using silicone rubber as the porous biomaterial component. The material has been shown to be biologically preferable for long term eye drainage implants and is well suited for the purposes of this invention.
    Figure 4 shows a plan view of a first embodiment of a combined IOP sensor and glaucoma drainage device 400 in accordance with the present invention. The device 400 includes a PIO sensor element 410 connected to an antenna element 420 as shown. The sensor element of PIO 410 also includes a signal processor (not shown) as will be described in more detail below: The sensor element of PIO 410 and the antenna element 420 are located between layers of a porous biocompatible material 430, for example the porous biocompatible material as described above. This will be described in more detail with reference to Figures 6 to 8 below. The biocompatible material 430 defines the overall shape of the device 400. In this embodiment, the antenna element 420 is shown to have a substantially circular profile.
    Yarns 470, 480 are provided for connecting the PIO sensor element 410 to the antenna element 420 as shown. As shown, the wires 470, 480 pass from the base plate portion 450 to the body portion 440 through the neck portion 460.
    As shown, the device 400 comprises a substantially circular body portion 440, a base plate portion 450 and a neck portion 460 which connects the body portion 440 to the base plate portion 450. As shown, the antenna member 420 is housed in the body portion 440 and the PIO sensor element 410 is housed in the base plate portion 450. The neck portion 460 provides an anchor point for the device when it is inserted into an eye as will be described in more detail. below.
    Typically, the approximate dimensions of the device are shown in Table 2 below.
    Table 2.
    The thickness of the porous section shown in Table 2 is that available for aqueous humor flow. It can be supplied in one or more layers. To further reduce the fibrotic reactions of the implant, the porous sections may have an uneven surface comprising a topography of "peaks and valleys" contacting the tissue where surface variations are often from about 100 μm to about 300 μm. relative to the average thickness of the porous section.
    It should be known that the dimensions shown in Table 3 may vary depending on the particular device 400, and the values given are given by way of example.
    Fig. 5 shows a plan view of a second embodiment of a combined IOP sensor and glaucoma drainage device 500. The device 500 comprises a PIO sensor element 510 connected to an antenna element 520 as shown. The sensor element of PIO 510 also includes a signal processor (not shown) as will be described in more detail below. The PIO sensor element 510 and the antenna element 520 are located between layers of porous biocompatible material 530 as described above. This is described in more detail with reference to Figures 6 to 8 below. The biocompatible material 530 defines the general shape of the device 500. In this embodiment, the antenna element 520 is shown to have a substantially rectangular profile.
    Wires 570, 580 are provided for connecting the PIO sensor element 510 to the antenna element 520 as shown. As shown, the wires 570 pass from the base plate portion 550 to the body portion 540 through the neck portion 560.
    As shown, the device 500 comprises a substantially rectangular body portion 540, a base plate portion 550 and a neck portion 560 which connects the body portion 540 to the base plate portion 550.
    As shown, the antenna element 520 is housed in the body portion 540 and the PIO sensor element 510 is housed in the base plate portion 550. The neck portion 560 provides an anchor point for the device when inserted. in an eye as will be described in more detail below.
    Typically, the approximate dimensions of the device 500 are shown in Table 3 below.
    Table 3
    The thickness of the porous section and the provision of an irregular surface should be understood in the same way as in Table 2.
    It should be understood that the dimensions shown in Table 3 may vary depending on the particular device 500, and the values are given by way of example. With the given dimensions, the resistance of these devices to the flow in the area of the base plate, through the neck and then out of the body was measured as being a drop in pressure between 0.6 and 0.3 mm Hg at a flow rate of 1 μΙ / min, thus allowing alternative sensor locations as indicated above. Figures 6 to 8 show sectional views through the device 500. The elements of the device 500 which have been described above with reference to Figure 5 have the same reference numbers.
    Figure 6 illustrates a cross-sectional view of the device 500 made through the base plate portion 550. This more clearly indicates the internal structure of the base plate portion 550. The PIO sensor element 510 is shown. Here, the sensor element of PIO 510 comprises a sensor 605 with a signal transceiver 610. The sensor, 605 and the signal transceiver 610 are embedded in an impervious protective material 620 having an opening 630 which is located above the PIO sensor element 510. The opening 630 allows fluid communication between the aqueous humor in the anterior chamber of the eye, through the porous biocompatible material 530, when the device 500 is implanted, and the sensor 605.
    The sensor 605 and the signal transceiver 610 are substantially contained within the base plate portion 550, and are substantially surrounded by the porous biocompatible material 530. An outer surface 640 of the porous biocompatible material 530 is also shown. . The surface 640 comprises open pores of the biocompatible material, the pores having apertures, as described above, which connect the inner pores within the porous biocompatible material 530.
    The sensor 605 reacts the pressure inside the eye. When using the exemplary dimensions for the above-mentioned devices 500, the pressure differences from the anterior chamber of the eye through the pores in the biocompatible material 530 to the PIO sensor element 510 are negligible. and an accurate reading of the IOP can be obtained.
    The exposed face of the PIO sensor element 510 can be protected from direct contact with the aqueous humor in the eye by using metallization with a biologically inert material, for example titanium. In addition, other sensor elements may be provided (not shown) that function to provide output signals indicative of one or more of the temperature, salinity, glucose level or drug concentration in the aqueous humor. .
    In a preferred embodiment of the present invention, the same biocompatible material used to form the porous form 530 which defines the device 500 can also be used in a solid form as part of the impermeable protective layer 620. This is advantageous for the manufacture practice of the device and reduces the number of various substances introduced into the eye.
    Figure 7 shows a cross-sectional view through the body portion. Here, parts 710; 720 of the antenna element 520 are shown incorporated within the impervious protective layer 620, the same protective layer 620 encapsulating the PIO sensor element 510 and the associated signal transceiver 610 as well as the wires 570, 580 and the antenna element 520. Although the same protective layer 620 can be used to encapsulate the PIO sensor element 510, the wires 570, 580 and the antenna element 520, it should be known that each of these elements can be encapsulated in separate protective layers (not shown). For example, the wires 570, 580 and the antenna element may be encapsulated in a highly flexible protective layer, the PIO sensor element 510 being encapsulated in another protective layer. It is also contemplated that the wires 570, 580 may also be in a separate protective layer-so long as they can still assume their function of connecting the PIO sensor element 510 to the antenna 520. Where the wire 580 passes through sections of the antenna 520, the conductors are electrically separated by an insulating layer 810 as shown in FIG. 8. This insulating layer 810 may be formed as a part of 620 or by other insulating means, by example a parylene coating.
    Parts 710 and 720 correspond to an induction loop (not shown) of the conductive elements 730 incorporated within the impermeable protective material layer 620. The outer ends of the loop are electrical continuity of the wires 570, 580. For the most efficient performance of power transfer and data communication, the antenna element 520 is preferably arranged to enclose the largest practicable area within the boundaries of the body portion 540. Note that, although the antenna element 520 is described as a spiral, other configurations may be used, for example a plurality of concentric loops connected together at their outer ends to the wires 570, 580 as described above. The spiral, shown for clarity as occupying most of the face area 540, may advantageously be more closely confined to the outer perimeter.
    The wires 570, 580 and the antenna element 520 may be formed by highly flexible gold conductors embedded in the porous biocompatible material forming the protective layer 620. Such conductors may be manufactured using known electronic assembly techniques, by for example, as described by WS Wang and A Salleo, in an article entitled "Flexible Electronics: Materials and Applications", Springer, 2009.
    The required degree of flexibility of these leads is determined in order to minimize the force exerted on the implant to conform to the curvature of the sclera surface of the eye. With the dimensions shown in Table 3, to correspond to the curvature of the human eye, the body part containing the antenna must deflect about 0.7 mm along its length. Using the specific silicone rubber identified in the first example of the above process, the porous material prepared therefrom has a measured tensile modulus of elasticity of 250 kPa, or about 9% of that of the form solid. The application of standard plate deflection formulas shows that the deflection of the 0.7 mm body portion of the device results in a tissue reaction pressure of less than 100 Pa due to the porous section using a thickness representative of 0, 3 mm. To minimize tissue stress, the porous material and antenna composite should not increase this by a factor of more than 5 and preferably not more than 2 times.
    As a comparison, the non-porous silicone drainage tube used in the Molteno device has a diameter of 0.64 mm and when it is shaped similar to the curvature of the eye, the pressure exerted on the surrounding tissue is about 15 times that exerted with the porous drain.
    Figure 8 shows a longitudinal sectional view of the device 500. Here, one can see the PIO sensor element 510, the antenna element 520 and the wires 570, 580 encapsulated within the impermeable protective material layer 620. The opening 630 is shown inside the porous biocompatible material 530. The outer surface 640 of the material 530 is also shown.
    Although FIGS. 6 to 8 refer to the integrated ICD sensor and drainage device 500 shown in FIG. 5, it is to be understood that the construction of the IOP sensor and drainage device 400 shown in FIG. 4 will be substantially the same. In all cases, the cross section of devices 400 and 500, after deduction of the space occupied by waterproof encapsulation 620, will provide drainage areas 530 substantially equivalent to those of Tables 2 and 3.
    In the embodiments shown in Figures 4 to 8, the base plate portion 450, 550 is formed for placement within the anterior chamber of the eye. The neck portion 460, 560 is placed through a surgical incision formed below the sclera in the anterior chamber. The body portion 440, 540 is surgically placed between the sclera 190 and the choroid 195 as described with reference to Figures 1 to 3 above. Once implanted in the eye, the aqueous humor flows in a controlled manner from the anterior chamber through the open pores in the porous biocompatible material 430, 530 which defines the base plate portion 450, 550, the neck portion 460, 560 and the body portion 440, 540 and in the space between the sclera 190 and the choroid 195 (Figs. 1 and 2) where it is absorbed into the choroidal bed (not shown) and returns to the circulation.
    The two integrated IOP sensor and drainage devices 460 and 500 as shown in FIGS. 4 to 8 can be constructed using the following steps. These more specifically apply to the porous material 530 formed from a silicone rubber material approved for long-term implantation, such as MED-6215 manufactured by Nusil Technologies LLC. Variations may be made to use other compositions as listed above.
    1. Build the entire PIO sensor element / antenna element assembly.
    2. Test the assembly before encapsulating it in the impermeable protective material layer 620. During the encapsulation process, the opening 630 is formed above the PIO sensor element 510.
    3. With the masked opening 630, apply a layer of untreated silicone rubber of a controlled thickness, such as, adhesion layer, to the encapsulated assembly.
    4. Apply the sheets of porous biocompatible material to the untreated (wet) silicone rubber adhesion layer, forming a sandwich structure with the IOP sensor / antenna element assembly between at least two sheets of porous biocompatible material . The thickness of the adhesion layer controls the extent to which the wet layer will penetrate ("wick") into the pores of the biocompatible material 530. The sheet thickness of the biocompatible material can be adjusted to provide the necessary cross-sectional area of the passages drain after occurrence of the wicking effect at a controlled depth of the pores.
    5. Treat the adhesion layer. This links the PIO sensor / antenna element assembly together in the biocompatible material that forms the drain for the integrated PIO sensor and drainage device according to the present invention.
    The above construction method can be varied to use primers if the impermeable protective layer 620 is formed from a material other than silicone rubber. The use of primers ensures that there will be adequate bonding between the protective layer and the biocompatible material.
    Any additional adhesion compositions, primary, etc. are specifically identifiable and well known for use in long-term medical implants.
    The outer portions of the porous biocompatible material in the sandwich should not be connected to each other in areas that do not adhere to the IOP / antenna element sensor assembly. Since the aqueous humor flow is mainly longitudinal through the drain (i.e. from 450 through 460 to 440), only the porous path in this direction must be substantially connected throughout and maintain a flow section such as described above. Thus, without detriment to the drain function, to maintain mechanical integrity and ease of surgical manipulation, adhesive spots may be applied to bond ("spot welded") the outer layers of the porous biocompatible material into areas outside a footprint defined by the PIO sensor / antenna element assembly.
    Having the inductive antenna element in the body portion and separated from the sensor in the base plate portion avoids having to locate a combination of the sensor element and the antenna element within the anterior chamber. In the present invention, as described above with reference to FIGS. 1 to 3, only the sensor element must be inside the anterior chamber. It should also be understood that while the sensor and antenna are conveniently shown as being widely symmetrical in the devices, they can be positioned in a variety of asymmetric arrangements without impairing their operation.
    This integrated device also has the advantage that the IOP measurements are independent of the ocular surface and the rigidity of the cornea. In addition, the accuracy of IOP measurements is not affected by other procedures that may need to be performed on the eye, for example keratoplasty or keratoprosthesis.
    Figure 9 illustrates a block diagram of a PIO 900 tracking system according to the present invention. The system 900 comprises a sensor / processor system 1000 which is located within the integrated PIO sensor and drainage device according to the present invention.
    The tracking system 900 also includes an external processor or external interrogation system 910 which includes an active interrogation system for the sensor / processor system 1000. The system 910 includes an inductive antenna element 915 which is energized by a transmitter assembly Receiver / receiver 920. Transmitter / receiver module 920 includes transmitter circuit 925 which is adapted to provide sufficient power levels to inductive antenna element 915 for retransmission, as a transmission signal 930, to inductive antenna element 1010 in the sensor / processor system 1000 as will be described in more detail below. It should be known that the inductive antenna element 1010 is equivalent to the antenna element 420 in FIG. 4 and to the antenna element 520 in FIGS. 5 to 8 described above.
    The transmission signal 930 comprises, firstly, a burst of energy at a selected frequency, the power level and the total energy delivered being sufficient, when they are received via the inductive antenna element 1010 in the system sensor / processor 1000, to activate the latter. Secondly, the transmission signal 930 is preferably coded to specifically address a sensor / processor system 1000 with which it is associated so as to allow the activation of the system 1000 only upon receipt of the correct code. Failure to integrate this coding capability would allow unwanted activation of the sensor / processor system 1000 by spurious signals and other risky situations. This differs from the Radio Frequency Identification (RFID) system where all tags within range are required to respond. It should be known that more than one sensor / processor system 1000 can be interrogated by an external polling system 910 as long as each system 1000 is polled with its unique code. This applies particularly to patients with bilateral glaucoma implants and can also be used in another aspect to provide the physician with a "boilerplate" access capability.
    In addition to the transmitter 925, the transmitter / receiver module 920 includes a receiver 935 which is adapted to filter and decode signals 940 transmitted by the inductive antenna element in the sensor / processor system 1000 as will be described in more detail. A buffer 945 connected to the receiver 935 and a 950 microprocessor is provided below. The buffer 945 receives measurements transmitted from the sensor / processor system 1000 and interfaces with the microprocessor 950.
    The transmitter / receiver module 920 also optionally includes an ambient condition and interface sensor 955 which can be used to sense atmospheric pressure and ambient temperature to apply corrections, if necessary, to the original measurements received by the receiver 935 in order to obtain a valid medically registered PJO value. In addition, the sensor 955 may also receive signals from a physiological monitor 960 which includes, without limitation, pulse rate and respiration.
    As shown, the transmitter 925, the receiver 935, the buffer 945 and the sensor 955 are connected to the microprocessor 950. The microprocessor 950 operates to provide: a) control of transmitted and received sequences for the transceiver module 920; b) interface and acknowledgment of PIO data from buffer 945; c) acknowledgment and application of ambient physiological conditions of the sensor 955; d) programmed calculation of the medically recorded PIO reading from each measurement sequence; e) a 965 wireless interface adapted for communication with a 970 cell phone or other similar device; f) an external interface means 975 such as that provided by the universal serial bus (USB) for downloading data and to establish the operating conditions for the device by a physician or other medically trained person; and g) managing the power consumption of the battery 980.
    Well known means, for example "Bluetooth" (trademark of the Bluetooth Special Interest Group) can be used for the 965 wireless interface with the 970 cell phone. The use of a software package programmed in the 970 cell phone allows a convenient display of patient information, alarms and physician contact and data transmission for the patient.
    During the programmed calculation of the medically recorded PIO reading, the microprocessor 950: - '* i) detects and rejects the corrupted data; ii) reduces the noise by averaging the readings on the received signals; iii) follows and tracks IOP trends, updating the patient data in the 900 tracking system with each successive record; iv) maintains a local indication of IOP registration and trend on a 990 display; and v) indicates to the patient by audible or other alarm means (not shown) excessively high or low IOP values.
    The external interrogation system 910 also includes a charger (not shown) to provide power for the 980 battery. However, an external power supply for charging is provided very conveniently via the USB 975 interface.
    Turning now to the sensor / processor system 1000, it comprises an inductive antenna element 1010 which interfaces with the inductive antenna element 915 of the external interrogation system 910. The antenna element 1010 is connected by the intermediate the wires 1015 to a transceiver protection switch 1020. The transceiver protection switch 1020 is connected to a decoder 1025, a detector 1030 and a transmitter 1035.
    The antenna element 1010 corresponds to the antenna elements 420, 520 as described above for FIGS. 4 and 5. The wires 1015 correspond to the wires 470, 480 (FIG. 4) and the wires 570, 580 (FIG. 5).
    The detector 1030 converts the received direct current signal to a voltage and current level adapted to the required operating power of the electronics in the integrated IOP sensor and drainage device according to the present invention. The power is then distributed to the other processing elements in the sensor / processor module 1000 through the connections 1036, 1040, 1050 as shown. An energy storage element 1055, preferably a capacitor, may be added to stabilize the power supply from the detector 1030, provide short-term power for the read signals from 1000, and provide a buffer against fluctuations. signal 930 transmitted by the external interrogation system 910 and received by the inductive antenna element 1010. Fluctuations may occur, for example due to changes in the relative positions of the inductive antenna elements 1010 and 915 due to the movements of the patient.
    The transceiver protection switch 1020 preferably provides: a) filtering to attenuate signals received from sources other than the external interrogation system 910; b) overload protection means for preventing damage to the implant by strong interference signals, such as, for example, due to patient use of a cell phone; and c) switching and protecting the detector 1030 and the decoder 1025 of the data read transmissions of the transmitter 1035.
    The sensor / processor system 1000 also includes an encoder 1060, an emitter control module 1065, an analog-to-digital converter (ADC) 1070, a sensor interface 1075 and a sensor assembly 1080. The sensor assembly 1080 comprises, an IOP sensor 1085 and a pressure reference 1090. The assembly 1080 corresponds to the sensor identified as 605 in FIGS. 6 and 8.
    The operation of the tracking system 900 will now be described in more detail.
    An inductive antenna element transmission signal 930 915 of the external interrogator 910 is received at the inductive antenna element 1010 and passed to the transceiver protection switch 1020 via the wires 1015, / The switch transceiver protection 1020 passes the signal to the power conversion detector 1030 as described above and to the decoder 1025. The decoder 1025 includes means for extracting the received address code and comparing it to a stored model. internal memory contained in a non-volatile memory (MNV) 1095. Upon detection of a code match, the decoder 1025 then provides timing and activation commands to enable sensor readings to be performed by the sensor assembly 1080 and transmitted to the external interrogation device 910.
    The decoder 1025 passes an activation signal to the transmitter control module 1065 which in turn passes a signal to the sensor interface 1075, the CAN 1070 and the sensor assembly 1080: It will be obvious that other possibilities, for example multiple code models, can be provided in MRV 1095, allowing unique codes for each combination of patient device / external interrogation system, as well as a separate code for medical access.
    More explicitly, the decoder 1025 provides commands to the sensor interface 1075 and later in the polling cycle to the transmitter control module 1065. When enabled, the sensor interface 1075 provides feedback to the sensor interface 1065. power to the sensor 1080 and buffers the resulting analog signal representing a pressure reading.
    The sensor element 1080 comprises a pressure sensitive component 1085 and a reference pressure component 1090. Without altering the intended operation, the pressure sensitive component 1085 uses a microelectromechanical sensor element (MEMS) which. deflects when pressure is applied to a surface (not shown). In one embodiment, the MEMS element forms a plate of a capacitor formed on a silicon substrate. In another embodiment, piezoresistive components that are responsive to pressure changes may be disposed on the deflectable member. In yet another embodiment, piezoelectric components such as those formed from polyvinylidene fluoride (PVDF) can be used.
    The pressure reference component 1090 comprises a sealed cavity (not shown) where a wall is formed by the pressure sensitive component 1085 and the other walls are formed by substantially rigid portions of the sensor 1080. The cavity may be evacuated for forming an absolute pressure sensor, or preferably, can be pre-pressurized to a predetermined reference pressure, for example standard atmospheric pressure.
    The output signal from the 1080 sensor, representing the IOP, is buffered and most often amplified by the sensor interface 1075 before being applied to the CAN 1070. The CAN 1070 converts the analog signals to digital signals, provides an electrical reference for the conversion and also provides temporary storage for the resulting PIO value. In certain embodiments of sensor embodiments, the CAN 1070 can also compensate for offsets or non-linearity of the output signal of the sensor 1080, for example by using a conversion table that is implemented in the manufacturing.
    In one embodiment, each IOP value
    medically recorded is determined from multiple readings performed at a rate of between about 3 / sec and about 20 / sec for a time interval of about 10 s to about 60 sec to allow averaging of IOP pulsations that may be be caused by blinking, breathing or vascular pulsations of the patient. This timing protocol is preferably pulse or other modulation of the transmit signal 930, thereby allowing the protocol to be easily modified to suit individual patients while minimizing the internal complexity of the set 1000. the intervals between each record can be determined by the external polling system 910.
    The encoder module 1060 encodes the PIO values received from the CAN 1070. An appropriate encoding method is the conversion of the PIO measurements to a binary encoding of at least 8 bits, allowing 256 IOP levels or a resolution of about 0, 2 mm Hg in an IOP range of 5 mm Hg to 50 mm Hg. Some code values may be reserved to indicate predetermined PIO values outside this range, for example less than 5 mm Hg or greater than 50 mm Hg Naturally, any range and appropriate value can be set and these ranges and values can be adapted to what is required for an individual patient in whom the IOP sensor and integrated drainage device is implanted. Each binary code may be attached to a defined header and other set of identification bits to form a standard length and format code string for highly reliable wireless transmission and reception. These codes are well known in the RFID domain and are not discussed further here.
    Under the control of the transmitter control module 1065, the code string is then used to modulate a transmission signal generated by the transmitter read module 1035. The modulated signal is passed to the transceiver protection switch. 1020 and then to the inductive antenna element 1010 for transmission as a read signal 940 for the external interrogation system 910, the
    Signal 940 being received by the antenna element 915.
    It is preferred that each individual reading of the multiple set described above be transmitted to the external interrogation system 910 in the intervals between the pulses of the transmission signal 930 from the antenna element 915. An exemplary pressure measurement sequence comprises: a) transmitting a transmission signal 930 of the antenna element 915 to the antenna element 1010, the transmission pulse being under the control of the external interrogation system 910; b) receiving the transmission signal by the antenna element 1010; c) conversion to the operating power for the sensor 1080 by the detector 1030 and activation of the device by recognition of the address code in the decoder 1025; d) reading of an IOP measurement by the 1080 sensor: e) encoding and transmission of the measured IOP measurement in electrical form via the CAN 1070, the encoder 1060 and the transceiver protection switch 1020 to the antenna element 1010; f) transmitting the read signal 940 of the antenna element 1010 to the antenna element 915 in the external interrogation system 910; and g) returning to a non-energized idle state until the next transmission signal 930 is received.
    The external interrogation system 910 can be physically realized as an accessory attached to an eyeglass frame that can be worn for long periods of time by a patient in whom the device has been implanted, a hand stick placed near the subject's eye or other convenient forms. It is necessary . know that the eyeglass frame will allow multiple IOP readings as long as the patient is wearing the glasses. However, if IOP measurements are to be performed at night, when the patient is asleep, an eye patch or modified sleep mask incorporating the external interrogator may be worn. Alternative means include forming the 915 antenna as a foldable sheet used beneath the patient's pillow. To compensate for the increased distance with respect to the implant antenna 1010 and the patient's movements, the area covered by 915 when it is provided in this form can be made larger than for a spectacle frame, a cover eye, a mask or the location of the wand.
    In addition, IOP measurements can be transmitted to a remote location, for example, a physician's office when the IOP values exceed predetermined threshold values by using cell phone or other communication system as it is known to be. knows well. IOP measurements can also be displayed for patient information, for example on their cell phone.
    It should be known that the system 910 includes the active part completing the detection function of the implanted device 200 (FIGS. 1 to 3) since the implant itself has no internal power supply. In the absence of 910 or in case of detection failure in 1000, no chemicals are present in the eye, which would be the case with an internal battery and the aqueous drainage function of the integrated implant does not exist. is not affected.
    Various modifications may come to the mind of tradespeople without departing from the spirit and scope of the invention.
    权利要求:
    Claims (37)
    [1]
    An integrated intraocular device comprising: an intraocular pressure sensing element; an antenna element; and an aqueous humor drainage element; characterized in that the drainage element comprises a porous biocompatible material including the intraocular pressure sensing element and the antenna element.
    [2]
    An integrated intraocular device according to claim 1, wherein the drainage element comprises a body portion housing the antenna element and a base plate portion housing the intraocular pressure sensing element.
    [3]
    An integrated intraocular device according to claim 2, wherein the body portion and the base plate portion are connected to each other by means of a smaller neck section portion which positions the drainage element in a position "in use" wanted inside the eye.
    [4]
    An integrated intraocular device according to claim 2 or 3, wherein the body portion is substantially circular and the antenna element comprises a circular spiral located within the circular body portion.
    [5]
    5: integrated intraocular device according to claim 2 or 3, wherein the body portion is substantially rectangular and the antenna element comprises a rectangular spiral located within the rectangular body portion.
    [6]
    An integrated intraocular device according to claim 4 or 5, wherein the antenna element is substantially arranged around the periphery of the body portion.
    [7]
    An integrated intraocular device according to any one of claims 2 to 6, wherein the antenna element and the intraocular pressure sensor element are connected by wires which pass between the body portion and the base plate portion.
    [8]
    An integrated intraocular device according to claim 7, further comprising at least one protective layer located between the intraocular pressure sensing element, the antenna element, the wires and the porous biocompatible material, the porous biocompatible material including each protective layer.
    [9]
    An integrated intraocular device according to claim 8, wherein a single protective layer is formed around the intraocular pressure sensing element, the antenna element and the wires, the single protective layer having an opening in proximity to the Intraocular pressure sensor element to allow the pressure of the aqueous humor to be measured through the porous biocompatible material.
    [10]
    An integrated intraocular device according to any one of the preceding claims, wherein the porous biocompatible material comprises a natural polymer.
    [11]
    An integrated intraocular device according to any one of claims 1 to 9, wherein the porous biocompatible material comprises a synthetic polymer.
    [12]
    The integrated intraocular device of claim 11, wherein the synthetic polymer comprises silicone rubber.
    [13]
    An integrated intraocular device according to any one of the preceding claims, wherein the average thickness of the porous biocompatible material is between 100 μm and 1000 μm.
    [14]
    The integrated intraocular device of claim 13, wherein the average thickness of the porous biocompatible material is between 100 μm and 500 μm.
    [15]
    The integrated intraocular device of claim 14, wherein the average thickness of the porous biocompatible material is between 200 μm and 500 μm.
    [16]
    An integrated intraocular device according to any one of the preceding claims, wherein the porous biocompatible material comprises substantially spherical open pores having an average pore diameter of between 20 μm and 90 μm.
    [17]
    The integrated intraocular device of claim 16, wherein the average pore diameter is between 20 μm and 40 μm.
    [18]
    The integrated intraocular device of claim 17, wherein the average pore diameter is between 25 μm and 30 μm.
    [19]
    The integrated intraocular device according to any one of claims 16 to 18, wherein the substantially spherical open pores have pore interconnections between 15% and 40% of the average pore diameter. χ1
    [20]
    The integrated intraocular device according to any one of the preceding claims, wherein the porous biocompatible material comprises an irregular outer surface having a topography of "peaks and valleys".
    [21]
    The integrated intraocular device of claim 20, wherein the surface variations of the irregular outer surface are between 100 μm and 300 μm based on the average thickness of the porous biocompatible material.
    [22]
    An integrated intraocular device according to any one of the preceding claims, wherein the porous biocompatible material provides a drain for the flow of aqueous humor with a resistance not exceeding 1 mm Hg pressure drop for a flow of 1 pl / min.
    [23]
    An integrated intraocular device according to any one of the preceding claims, wherein the antenna element comprises an inductive antenna element.
    [24]
    The integrated intraocular device of claim 23, wherein the antenna element is passive.
    [25]
    An integrated intraocular device according to any one of the preceding claims, wherein the intraocular pressure sensing element is passive.
    [26]
    The integrated intraocular device according to any one of the preceding claims, further comprising an intraocular pressure sensor processing system, the intraocular pressure sensor forming part of the intraocular pressure sensor processing system.
    [27]
    The integrated intraocular device of claim 26, wherein the intraocular pressure sensor processing system comprises a decoder for decoding signals received by the antenna element and a detector for obtaining power signals of the received signals. ^
    [28]
    The integrated intraocular device of claim 27, wherein the intraocular pressure sensor processing system further comprises an energy storage module for storing energy relative to the power signal derived from the received signals.
    [29]
    An integrated intraocular device according to any one of claims 26 to 28, wherein the intraocular pressure sensor processing system comprises an encoder for encoding signals to be transmitted by the antenna element.
    [30]
    30. Intraocular pressure monitoring system comprising: - an interrogation and treatment system; an integrated intraocular device according to any one of the preceding claims, the intraocular device being arranged to communicate wirelessly with the interrogation and processing system.
    [31]
    The intraocular pressure tracking system of claim 30, wherein the interrogation and processing system comprises a transceiver element for transmitting activation signals to the integrated intraocular device and for receiving signals corresponding to the pressure measurements. intraocular taken by the integrated intraocular device when it is activated.
    [32]
    The intraocular pressure tracking system of claim 31, wherein the interrogation and processing system comprises a communication module for transmitting intraocular pressure measurement data at a remote location.
    [33]
    33. Intraocular pressure monitoring system according to any one of claims 30 to 32, wherein the interrogation and treatment system is mounted in at least one pair of glasses, a baguette, a pillowcase and a sheet .
    [34]
    34. A method of monitoring intraocular pressure, the method comprising the steps of: a) implanting an integrated intraocular device according to any one of claims 1 to 29; and (b) determining intraocular pressure measurements using an intraocular pressure sensing element within the integrated intraocular device; characterized in that step a) comprises implanting the portion of the device comprising the intraocular pressure sensor element within the anterior chamber of the eye.
    [35]
    The intraocular pressure monitoring method of claim 34, wherein step a) comprises the steps of performing a limbal incision in the eye; placing the baseplate portion within the anterior chamber of the eye, the neck portion being located in the limbal incision; and position the body part inside the outer layers of the eye.
    [36]
    36. The method of monitoring the intraocular pressure of claim 35, wherein step a) further comprises positioning the body portion between the choroid and the sclera of the eye.
    [37]
    37. A method of monitoring intraocular pressure according to any of claims 34 to 36, wherein step b) comprises using an extracorporeal device to interface with the intraocular pressure sensor element to obtain an output. intraocular pressure measurements.
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    同族专利:
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    EP2517619A8|2012-12-26|
    CN103517667B|2016-11-09|
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    BE1020907B1|2019-09-16|
    US20120302861A1|2012-11-29|
    EP2517619A1|2012-10-31|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US6102045A|1994-07-22|2000-08-15|Premier Laser Systems, Inc.|Method and apparatus for lowering the intraocular pressure of an eye|
    US5704907A|1994-07-22|1998-01-06|Wound Healing Of Oklahoma|Method and apparatus for lowering the intraocular pressure of an eye|
    US5520631A|1994-07-22|1996-05-28|Wound Healing Of Oklahoma|Method and apparatus for lowering the intraocular pressure of an eye|
    US5807406A|1994-10-07|1998-09-15|Baxter International Inc.|Porous microfabricated polymer membrane structures|
    US5882327A|1997-04-17|1999-03-16|Jacob; Jean T.|Long-term glaucoma drainage implant|
    US20050119601A9|1999-04-26|2005-06-02|Lynch Mary G.|Shunt device and method for treating glaucoma|
    TR200103098T2|1999-04-26|2002-04-22|Gmp Vision Solutions, Inc.|Rotation tool and method for glaucoma treatment.|
    US6699210B2|1999-04-27|2004-03-02|The Arizona Board Of Regents|Glaucoma shunt and a method of making and surgically implanting the same|
    US6702848B1|1999-07-20|2004-03-09|Peter Paul Zilla|Foam-type vascular prosthesis with well-defined anclio-permissive open porosity|
    US6579235B1|1999-11-01|2003-06-17|The Johns Hopkins University|Method for monitoring intraocular pressure using a passive intraocular pressure sensor and patient worn monitoring recorder|
    US6939299B1|1999-12-13|2005-09-06|Kurt Petersen|Implantable continuous intraocular pressure sensor|
    US6881198B2|2001-01-09|2005-04-19|J. David Brown|Glaucoma treatment device and method|
    US7678065B2|2001-05-02|2010-03-16|Glaukos Corporation|Implant with intraocular pressure sensor for glaucoma treatment|
    KR20040036912A|2001-08-16|2004-05-03|지엠피 비젼 솔루션즈 인코포레이티드|Improved shunt device and method for treating glaucoma|
    CA2483859C|2002-05-06|2009-11-17|Biomet Deutschland Gmbh|Method of preparing porous calcium phosphate granules|
    US7488303B1|2002-09-21|2009-02-10|Glaukos Corporation|Ocular implant with anchor and multiple openings|
    US7037335B2|2002-11-19|2006-05-02|Eagle Vision, Inc.|Bulbous scleral implants for the treatment of eye disorders such as presbyopia and glaucoma|
    US7160264B2|2002-12-19|2007-01-09|Medtronic-Xomed, Inc.|Article and method for ocular aqueous drainage|
    EP1433489A1|2002-12-23|2004-06-30|Degradable Solutions AG|Biodegradable porous bone implant with a barrier membrane sealed thereto|
    US20040225250A1|2003-05-05|2004-11-11|Michael Yablonski|Internal shunt and method for treating glaucoma|
    AU2004247272A1|2003-06-16|2004-12-23|Solx, Inc.|Shunt for the treatment of glaucoma|
    WO2005032418A2|2003-10-01|2005-04-14|University Of Washington|Novel porous biomaterials|
    JP5090742B2|2003-12-05|2012-12-05|インフォーカスリミテッドライアビリティーカンパニー|Improved glaucoma transplant device|
    US7594899B2|2004-12-03|2009-09-29|Innfocus, Llc|Glaucoma implant device|
    US7837644B2|2004-12-03|2010-11-23|Innfocus, Llc|Glaucoma implant device|
    CA2927921C|2006-01-17|2019-06-04|Transcend Medical, Inc.|Glaucoma treatment device|
    ES2396088T3|2006-04-26|2013-02-19|Eastern Virginia Medical School|Systems to monitor and control the internal pressure of an eye or a body part|
    WO2008061043A2|2006-11-10|2008-05-22|Glaukos Corporation|Uveoscleral shunt and methods for implanting same|
    US7677107B2|2007-07-03|2010-03-16|Endotronix, Inc.|Wireless pressure sensor and method for fabricating wireless pressure sensor for integration with an implantable device|
    EP2173289A4|2007-07-17|2010-11-24|Transcend Medical Inc|Ocular implant with hydrogel expansion capabilities|
    CA2695454C|2007-08-23|2016-09-20|Purdue Research Foundation|Intra-ocular pressure sensor|
    US20110082385A1|2008-04-17|2011-04-07|Yale University|Method for implanting intraocular pressure sensor|
    US8926524B2|2008-06-02|2015-01-06|California Institute Of Technology|System, apparatus and method for biomedical wireless pressure sensing|
    EP2789318A3|2009-03-26|2015-02-18|Abbott Medical Optics Inc.|Glaucoma shunts with flow management and improved surgical performance|
    CN102711593A|2009-09-18|2012-10-03|奥尔托梅姆斯有限公司|Implantable mems intraocular pressure sensor devices and methods for glaucoma monitoring|
    US8257295B2|2009-09-21|2012-09-04|Alcon Research, Ltd.|Intraocular pressure sensor with external pressure compensation|
    US8545431B2|2009-09-21|2013-10-01|Alcon Research, Ltd.|Lumen clearing valve for glaucoma drainage device|
    WO2011065987A1|2009-11-25|2011-06-03|Healionics Corporation|Granules of porous biocompatible materials|
    WO2011127395A1|2010-04-08|2011-10-13|Healionics Corporation|Implantable medical devices having microporous surface layers and method for reducing foreign body response to the same|
    CN101766473B|2010-02-09|2011-09-07|北京大学人民医院|System for monitoring intraocular pressure|
    ES2528350T3|2011-01-14|2015-02-09|Ecole Polytechnique Federale De Lausanne |Apparatus and method for the treatment of excess intraocular fluid|
    EP2517619B1|2011-04-27|2013-05-22|Istar Medical|Improvements in or relating to glaucoma management and treatment|
    US20120310137A1|2011-06-02|2012-12-06|Silvestrini Thomas A|Eye shunt with porous structure|TR200103098T2|1999-04-26|2002-04-22|Gmp Vision Solutions, Inc.|Rotation tool and method for glaucoma treatment.|
    US6638239B1|2000-04-14|2003-10-28|Glaukos Corporation|Apparatus and method for treating glaucoma|
    US7431710B2|2002-04-08|2008-10-07|Glaukos Corporation|Ocular implants with anchors and methods thereof|
    AT390106T|2001-04-07|2008-04-15|Glaukos Corp|GLAUKOM-STENT FOR GLAUCOMA TREATMENT|
    US7867186B2|2002-04-08|2011-01-11|Glaukos Corporation|Devices and methods for treatment of ocular disorders|
    US7331984B2|2001-08-28|2008-02-19|Glaukos Corporation|Glaucoma stent for treating glaucoma and methods of use|
    US10010272B2|2010-05-27|2018-07-03|Profusa, Inc.|Tissue-integrating electronic apparatus|
    CN103260501B|2010-10-06|2015-09-02|普罗弗萨股份有限公司|Tissue integration sensor|
    JP6066637B2|2011-09-21|2017-01-25|ゼネラル・エレクトリック・カンパニイ|System for monitoring the physiological status of multiple infants|
    EP2517619B1|2011-04-27|2013-05-22|Istar Medical|Improvements in or relating to glaucoma management and treatment|
    US20130090534A1|2011-09-13|2013-04-11|Thomas W. Burns|Intraocular physiological sensor|
    WO2013148275A2|2012-03-26|2013-10-03|Glaukos Corporation|System and method for delivering multiple ocular implants|
    US9358156B2|2012-04-18|2016-06-07|Invantis, Inc.|Ocular implants for delivery into an anterior chamber of the eye|
    US9291586B2|2012-05-05|2016-03-22|Board Of Regents, The University Of Texas System|Passive wireless self-resonant sensor|
    US9295389B2|2012-12-17|2016-03-29|Novartis Ag|Systems and methods for priming an intraocular pressure sensor in an intraocular implant|
    US9528633B2|2012-12-17|2016-12-27|Novartis Ag|MEMS check valve|
    US9572712B2|2012-12-17|2017-02-21|Novartis Ag|Osmotically actuated fluidic valve|
    US8874182B2|2013-01-15|2014-10-28|Google Inc.|Encapsulated electronics|
    US10219696B2|2013-03-07|2019-03-05|The Board Of Trustees Of The Leland Stanford Junior University|Implantable pressure sensors for telemetric measurements through bodily tissues|
    US10016132B2|2013-03-07|2018-07-10|The Board Of Trustees Of The Leland Stanford Junior University|Implantable micro-fluidic device for monitoring of intra-ocular pressure|
    US10517759B2|2013-03-15|2019-12-31|Glaukos Corporation|Glaucoma stent and methods thereof for glaucoma treatment|
    US9113829B2|2013-03-27|2015-08-25|Google Inc.|Systems and methods for encapsulating electronics in a mountable device|
    US9962084B2|2013-06-15|2018-05-08|Purdue Research Foundation|Wireless interstitial fluid pressure sensor|
    US9814387B2|2013-06-28|2017-11-14|Verily Life Sciences, LLC|Device identification|
    US9901247B2|2013-06-28|2018-02-27|Verily Life Sciences Llc|Methods for adhering a substrate to a polymer layer|
    US20150057523A1|2013-08-21|2015-02-26|Alcon Research, Ltd.|Systems and methods for priming an intraocular pressure sensor chamber|
    US9283114B2|2013-08-24|2016-03-15|Novartis Ag|Systems and methods for priming a microfluidic chamber|
    US20150057594A1|2013-08-24|2015-02-26|Alcon Research, Ltd.|Bubble-free microfluidic valve systems and methods|
    US9681983B2|2014-03-13|2017-06-20|Novartis Ag|Debris clearance system for an ocular implant|
    US9603742B2|2014-03-13|2017-03-28|Novartis Ag|Remote magnetic driven flow system|
    RU2562553C1|2014-04-30|2015-09-10|Общество с ограниченной ответственностью "Вертикаль-М" |Porous composite drain tube for surgical management of glaucoma|
    US20150342875A1|2014-05-29|2015-12-03|Dose Medical Corporation|Implants with controlled drug delivery features and methods of using same|
    US9743885B1|2014-06-12|2017-08-29|Verily Life Sciences Llc|Method of two-step parylene patterning and etching to release a parylene sandwiched device|
    DE102014212457A1|2014-06-27|2015-12-31|Implandata Ophthalmic Products Gmbh|Implant for the determination of intraocular pressure|
    CN106714664A|2014-07-01|2017-05-24|注射感知股份有限公司|Hermetically sealed implant sensors with vertical stacking architecture|
    WO2016004223A1|2014-07-01|2016-01-07|Cao Ariel|Methods and devices for implantation of intraocular pressure sensors|
    US10201451B2|2014-08-29|2019-02-12|Camras Vision Inc.|Device and method for reducing intraocular pressure|
    US10342702B2|2014-08-29|2019-07-09|Camras Vision Inc.|Apparatus and method for reducing intraocular pressure|
    US10842916B2|2015-06-24|2020-11-24|Healionics Corporation|Injectable porous device for treatment of dry and wet age-related macular degeneration or diabetic retinopathy|
    CA2995240A1|2015-08-14|2017-02-23|Ivantis, Inc.|Ocular implant with pressure sensor and delivery system|
    CN105030374B|2015-08-26|2017-10-24|王少立|It is a kind of can long term monitoring human body physiological parameter intelligent artificial lens|
    US10524958B2|2015-09-30|2020-01-07|Alievio, Inc.|Method and apparatus for reducing intraocular pressure|
    CN108430404B|2015-12-24|2021-08-24|伊斯塔尔医疗公司|Ocular implant system|
    CA3024891A1|2016-05-31|2017-12-07|Qura, Inc.|Implantable intraocular pressure sensors and methods of use|
    EP3621512A4|2017-05-12|2021-01-06|California Institute of Technology|Implantable extracompartmental pressure sensor|
    CN107473175B|2017-08-15|2019-09-06|薛宁|A kind of nerve electrode and its manufacture craft and application based on porous silicon and polymer|
    US11116625B2|2017-09-28|2021-09-14|Glaukos Corporation|Apparatus and method for controlling placement of intraocular implants|
    US20190150736A1|2017-11-17|2019-05-23|David A. Wallace|System and Method Enabling Affordable Measurement, Monitoring and Reporting of Intra-Ocular Pressure, Combined with System for Topical Medication Delivery, appropriate for Office or Home-Based Use|
    DE102018203424A1|2018-03-07|2019-09-12|Carl Zeiss Meditec Ag|Shunt implant|
    CN108992038A|2018-08-10|2018-12-14|清华大学|System for monitoring intraocular pressure and intraocular pressure monitoring method|
    WO2021127630A1|2019-12-20|2021-06-24|Glaukos Corporation|On-demand intraocular physiological sensor with trabecular bypass flow|
    DE102020211175A1|2020-09-04|2022-03-10|Carl Zeiss Meditec Ag|Stent implant for glaucoma treatment by drainage of aqueous humor from the anterior chamber|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    EP11163979.5A|EP2517619B1|2011-04-27|2011-04-27|Improvements in or relating to glaucoma management and treatment|
    EP11163979|2011-04-27|
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