Patent Grant
11523938
This disclosure generally relates to intraocular pressure reduction and more specifically to systems, devices and methods for delivering an intraocular implant to the suprachoroidal space within an eye to treat glaucoma, ocular hypertension and/or other ocular disorders.
A human eye is a specialized sensory organ capable of light reception and is able to receive visual images. Aqueous humor is a transparent liquid that fills at least the region between the cornea, at the front of the eye, and the lens. A trabecular meshwork, located in an anterior chamber angle, which is formed between the iris and the cornea, normally serves as a drainage channel for aqueous humor from the anterior chamber so as to maintain a balanced pressure within the anterior chamber of the eye.
Glaucoma is a group of eye diseases encompassing a broad spectrum of clinical presentations, etiologies, and treatment modalities. Glaucoma causes pathological changes in the optic nerve, visible on the optic disk, and it causes corresponding visual field loss, resulting in blindness if untreated. Lowering intraocular pressure is a major treatment goal in glaucomas.
In glaucomas associated with an elevation in eye pressure (intraocular hypertension), a main source of resistance to outflow is typically in the trabecular meshwork. The tissue of the trabecular meshwork normally allows the aqueous humor (hereinafter also referred to as “aqueous”) to enter Schlemm's canal, which then empties into aqueous collector channels in the posterior wall of Schlemm's canal and then into aqueous veins, which form the episcleral venous system. Aqueous is continuously secreted by a ciliary body around the lens, so there is a constant flow of aqueous from the ciliary body to the anterior chamber of the eye. Pressure within the eye is determined by a balance between the production of aqueous and its exit through the trabecular meshwork (major route) and uveoscleral outflow (minor route) pathways. The portion of the trabecular meshwork adjacent to Schlemm's canal (the juxtacanilicular meshwork) can cause most of the resistance to aqueous outflow.
Glaucoma is broadly classified into two categories: closed-angle glaucoma, also known as angle closure glaucoma, and open-angle glaucoma. Closed-angle glaucoma is caused by closure of the anterior chamber angle by contact between the iris and the inner surface of the trabecular meshwork. Closure of this anatomical angle prevents normal drainage of aqueous from the anterior chamber of the eye.
Open-angle glaucoma is any glaucoma in which the exit of aqueous through the trabecular meshwork is diminished while the angle of the anterior chamber remains open. For most cases of open-angle glaucoma, the exact cause of diminished filtration is unknown. Primary open-angle glaucoma is the most common of the glaucomas, and is often asymptomatic in the early to moderately advanced stages of glaucoma. Patients may suffer substantial, irreversible vision loss prior to diagnosis and treatment.
Most current therapies for glaucoma are directed toward decreasing intraocular pressure. Medical therapy includes topical ophthalmic drops or oral medications that reduce the production of aqueous or increase the outflow of aqueous. However, drug therapies for glaucoma are sometimes associated with significant side effects. The most frequent and perhaps most serious drawback to drug therapy, especially the elderly, is patient compliance. Patients often forget to take their medication at the appropriate times or else administer eye drops improperly, resulting in under- or overdosing. Patient compliance is particularly problematic with therapeutic agents requiring dosing frequencies of three times a day or more, such as pilocarpine. Because the effects of glaucoma are irreversible, when patients dose improperly, allowing ocular concentrations to drop below appropriate therapeutic levels, further permanent damage to vision occurs.
As such, a need exists for a more facile, convenient, less invasive, and less traumatic means of delivering an intraocular pressure controlling implant into an eye while providing a cost-effective but safe surgical procedure. It is one advantage of certain embodiments of the invention(s) disclosed herein to provide delivery devices, systems and methods for inserting an implant into an eye. The delivery or inserter devices or systems can be used to dispose or implant an ocular stent or implant, such as a shunt, in communication with the suprachoroidal space, uveoscleral outflow pathway (sometimes referred to as uveal scleral outflow pathway) and/or supraciliary space of the eye. The implant can drain fluid from an anterior chamber of the eye to a physiologic outflow path of the eye, such as, the suprachoroidal space, uveoscleral outflow pathway, or supraciliary space. Alternatively, or in addition, the implant can elute a drug or therapeutic agent. The delivery or inserter devices or systems can be used in conjunction with other ocular surgery, for example, but not limited to, cataract surgery through a preformed corneal incision, or independently with the inserter configured to make a corneal or limbal incision. The implant can be preloaded with or within the inserter to advantageously provide an operator-friendly package, such as a sterile package, for convenient use by a surgeon, doctor or operator. In some embodiments, the implant is not preloaded within the delivery device or inserter and/or is not provided within the same package as the delivery device or inserter.
While a majority of the aqueous leaves the eye through the trabecular meshwork and Schlemm's canal, it is believed that at least about 10 to about 20 percent of the aqueous in humans leaves through the uveoscleral pathway. The degree with which uveoscleral outflow contributes to the total outflow of the eye appears to be species dependent. As used herein, the term “uveoscleral outflow pathway” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the space or passageway whereby aqueous exits the eye by passing through the ciliary muscle bundles located at or near an angle of the anterior chamber and into the tissue planes between the choroid and the sclera, which extend posteriorly to the optic nerve. From these tissue planes, it is believed that the aqueous travels through the surrounding scleral tissue and drains via the scleral and conjunctival vessels, or is absorbed by the uveal blood vessels.
As used herein, the term “supraciliary space” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the portion of the uveoscleral pathway through the ciliary muscle and between the ciliary body and the sclera, and the term “suprachoroidal space” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the portion of the uveoscleral outflow pathway between the choroid and sclera.
The term “implant” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to drainage shunts, stents, sensors, drug delivery implants, drugs, therapeutic agents, fluids, or any other device or substance capable of being permanently or temporarily inserted within an eye and left within a body after removal of a delivery instrument.
As used herein, “implants” refers to ocular implants which can be implanted into any number of locations in the eye. In some embodiments, the ocular implants are drainage implants designed to facilitate or provide for the drainage of aqueous humor from the anterior chamber of an eye into a physiologic outflow pathway in order to reduce intraocular pressure. In some embodiments, the implant can be configured to provide a fluid flow path for draining aqueous humor from the anterior chamber to a uveoscleral outflow pathway. In some embodiments, the aqueous humor is diverted to the supraciliary space and/or the suprachoroidal space of the uveoscleral outflow pathway.
If desired, more than one implant of the same or different type may be implanted. For example, the implants disclosed herein may be used in combination with trabecular bypass shunts, such as those disclosed in U.S. Patent Publication 2004/0050392, filed Aug. 28, 2002, and those described in U.S. Patent Publication 2005/0271704, filed Mar. 18, 2005, the entire contents of each of which are incorporated herein by reference. Additionally, implantation may be performed in combination with other surgical procedures, such as cataract surgery. All or a portion of the implant may be coated, e.g. with heparin, preferably in the flow path, to reduce blood thrombosis or tissue restenosis.
In some embodiments, at least some slight and/or predetermined flexibility is provided to an obturator, or trocar, of an implant delivery system for ocular tissue penetration and to conform with an eye's structure and anatomy at or along the pathway to an implantation site. In some embodiments, at least some slight and/or predetermined flexibility is provided to an implant or stent to conform with the eye's structure and anatomy at or along the pathway to an implantation site. The terms “obturator” and “trocar” are used interchangeably herein, and in addition to their ordinary meanings, may refer to an elongate instrument with a generally rounded or non-sharp distal tip.
In accordance with several embodiments, an ocular implant delivery system includes a delivery device (e.g., an applicator or inserter) and an ocular implant. The implant may be preloaded on or within the delivery device and provided as a kit within a package for convenient use by an operator. The delivery device may include a generally elongated outer housing that is ergonomically contoured. The delivery device may also include an elongated insertion sleeve partially disposed in the outer housing and having a non-linear exposed distal portion extending out of a distal end of the housing. The non-linear exposed distal portion of the insertion sleeve may have a curvature adapted to conform to an anatomical curvature of the eye, such as the cornea and/or sclera. The delivery device may include an obturator, or trocar, passing through a lumen of the insertion sleeve and having a non-linear distal portion extending beyond the non-linear distal portion of the insertion sleeve. In one embodiment, the obturator has a rounded, blunt or non-faceted distal end. In use, the non-linear distal portion of the obturator is adapted to provide access to a suprachoroidal space through a ciliary muscle attachment. In one embodiment, the access is provided without dissecting a ciliary body portion at the anterior chamber angle from the sclera but instead is provided by insertion of the obturator through a fibrous band of the ciliary muscle. In some embodiments, the non-linear distal portion of the obturator is flexible and has a curvature adapted to maintain pressure against the sclera during insertion into the suprachoroidal space. The delivery device may also include a trigger operatively coupled to the obturator such that movement of the trigger towards a proximal end of the housing retracts the obturator within the insertion sleeve, thereby deploying the implant off of the obturator.
The implant is adapted to be disposed on the non-linear portion of the obturator and positioned distally of the non-linear distal portion of the insertion sleeve prior to insertion of the delivery device into an eye. For example, the implant may be loaded on the obturator by inserting a distal end of the obturator within a lumen of the implant and advancing the implant over the obturator or advancing the obturator toward a distal end of the implant. In some embodiments, in use, a distal end of the insertion sleeve is adapted to react against a proximal end of the implant as the obturator is being retracted to deliver the implant. The insertion sleeve may be sized to extend through a corneal incision and into an anterior chamber of the eye. In some embodiments, the implant has a curvature which substantially matches the curvature of the non-linear portion of the obturator. In some embodiments, the curvature of the non-linear distal portion of the obturator and/or the implant is larger than a diameter of the eye.
In use, the trigger may be manually controlled and held in a forward position, and retracted in a backward motion to cause delivery of the implant once a distal end of the implant has been advanced to a desired location within the suprachoroidal space, wherein the backward motion of the obturator is adapted to prevent against over-insertion of the implant within the suprachoroidal space. In some embodiments, a distal tip of the obturator is rounded so as not to cause scraping of the sclera while still being adapted to provide access to the suprachoroidal space through the ciliary muscle attachment.
In some embodiments, the implant is an elongate tube having an outer diameter of the implant is between 300 and 400 microns. In some embodiments, a distal portion of the implant includes a plurality of circumferential retention members. A distal tip of the implant may be tapered. A proximal end of the implant may include a flange. In some embodiments, the delivery device includes reuse prevention structures configured to limit use to a single use. For example, the reuse prevention structures ma include a pair of glue blocks mounted on each side of a trigger of the obturator adapted to melt upon sterilization to lock the trigger against further use.
In accordance with several embodiments, an ocular implant delivery system includes a delivery device, applicator or inserter having a generally elongated outer housing that is ergonomically contoured and an elongated insertion needle partially disposed in the outer housing and having a non-linear exposed distal portion. The delivery device may further include an implant pusher tube extending through a lumen of the elongated insertion needle and having a non-linear distal portion. In one embodiment, the delivery device includes an obturator passing through a lumen of the pusher tube and having a non-linear distal portion. In use, the non-linear distal portion of the obturator may be adapted to provide access to a suprachoroidal space through a ciliary muscle attachment. The non-linear distal portion of the obturator may be flexible and have a curvature adapted to maintain pressure against the sclera during insertion into the suprachoroidal space. The delivery device may also include a pusher tube trigger operatively coupled to the pusher tube such that movement of the pusher tube trigger towards a proximal end of the housing retracts the obturator toward the housing. In use, a distal end of the pusher tube may be adapted to react against a proximal end of an implant loaded on to the obturator as the obturator is being retracted within the housing to deliver the implant.
In one embodiment, the insertion needle is a corneal penetration needle (e.g., a 25±5 gauge needle) adapted to create a self-sealing corneal incision (e.g., at or near the corneal limbus). The non-linear portions of the insertion needle, pusher tube and/or obturator may have a substantially matching curvature. The system may also include an implant preloaded onto the obturator and provided together with the delivery device in a kit or packaging. The implant may have a curvature that substantially conforms to or matches, the curvatures of the insertion needle, pusher tube and obturator.
In some embodiments, the pusher tube trigger is operatively coupled to a trigger of the obturator. The obturator may be advanceable and retractable by actuation of the trigger of the obturator. In some embodiments, when the pusher tube is fully advanced the pusher tube is locked to prevent further motion. The delivery device may include reuse prevention structures designed and/or adapted to limit use of the delivery device to a single use. For example, the reuse prevention structures may include a pair of glue blocks mounted on each side of the pusher tube trigger adapted to melt upon sterilization to lock the pusher tube trigger against further use.
In accordance with several embodiments, an ocular implant delivery device includes a generally elongated outer housing that is ergonomically contoured and an elongated insertion sleeve partially disposed in the outer housing and having a non-linear exposed distal portion. The ocular implant delivery device may also include a tubular support member surrounding a portion of the elongated insertion sleeve. The tubular support member may have a proximal end within the outer housing and a distal end extending outside of the outer housing. The tubular support member may be configured to facilitate coupling of the elongated insertion sleeve to the outer housing. The tubular support member may surround a portion of the elongated insertion sleeve. The delivery device may also include an obturator passing through a lumen of the elongated insertion sleeve and having a non-linear distal portion extending beyond the non-linear exposed distal portion of the elongated insertion sleeve and a trigger operatively coupled to the obturator such that actuation of the trigger retracts the obturator into the insertion sleeve, thereby causing a proximal end of an implant disposed on the non-linear portion of the obturator to react against a distal end of the insertion sleeve so as to facilitate deployment of the implant from the obturator. In some embodiments, the non-linear distal portion of the obturator carrying the implant is configured to be advanced into a suprachoroidal space of an eye and the non-linear distal portion of the obturator has a curvature configured to be larger than a diameter of the eye.
For purposes of summarizing embodiments of the invention(s), certain aspects, advantages and novel features of the invention have been described herein above. Of course, it is to be understood that not necessarily all such advantages may be achieved in accordance with any particular embodiment of the invention. Thus, the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught or suggested herein without necessarily achieving other advantages as may be taught or suggested herein.
All of these embodiments are intended to be within the scope of the invention herein disclosed. These and other embodiments of the invention will become readily apparent to those skilled in the art from the following detailed description of the preferred embodiments having reference to the attached figures, the invention not being limited to any particular preferred embodiment(s) disclosed.
Having thus summarized the general nature of some of the embodiments of the invention(s) and some of their features and advantages, certain preferred embodiments and modifications thereof will become apparent to those skilled in the art from the detailed description herein having reference to the figures that follow, which are intended to illustrate and not to limit the disclosure.
The preferred embodiments of the invention described herein relate generally to intraocular pressure reduction and, in particular, to systems, devices and methods for delivering an intraocular implant to the suprachoroidal space, supraciliary space or other anatomical space within a uveoscleral outflow pathway of an eye to treat glaucoma, ocular hypertension and/or other ocular disorders.
While the description sets forth various embodiment specific details, it will be appreciated that the description is illustrative only and should not be construed in any way as limiting the invention. Furthermore, various applications of the invention, and modifications thereto, which may occur to those who are skilled in the art, are also encompassed by the general concepts described herein.
The anterior chamber 32 of the eye 10, which is bound anteriorly by the cornea 36 and posteriorly by the iris 44 and the lens 48, is filled with aqueous humor or aqueous fluid (which may be simply referred to herein as aqueous). Aqueous is produced primarily by the ciliary bodies 46 and flows into the posterior chamber, bounded posteriorly by the lens 48 and anteriorly by the iris 44. The aqueous humor then flows anteriorly through the pupil 42 and into the anterior chamber 32 until it reaches an anterior chamber angle 50, formed generally between the iris 44 and the cornea 36.
In a normal eye, at least some of the aqueous humor drains from the anterior chamber 32 through a trabecular meshwork into Schlemm's canal and thereafter through a plurality of collector ducts and aqueous veins, which merge with blood-carrying veins, and into systemic venous circulation. Intraocular pressure is maintained by an intricate balance between secretion and outflow of aqueous humor in the manner described above. Glaucoma is, in most cases, characterized by an excessive buildup of aqueous humor in the anterior chamber 32, which leads to an increase in intraocular pressure. Fluids are relatively incompressible, and thus, intraocular pressure is distributed relatively uniformly throughout the eye 10.
The choroid 40 is a vascular layer of the eye 10 located between the sclera 38 and a retina (not identified in
Another existing aqueous drainage route is provided through a suprachoroidal space 34, which is a space or region generally defined between the sclera 38 and the choroid 40. The suprachoroidal space 34 is exposed to the anterior chamber 32 through the anterior chamber angle 50. The tissue connection between the anterior chamber 32 and suprachoroidal space 34 is generally via a fibrous attachment zone 60 generally disposed between a scleral spur 62 and iris processes 64 and/or ciliary muscle 66, which is a part of the choroid 40.
Certain embodiments of suprachoroidal implants, delivery devices, associated components and suprachoroidal implantation methods and procedures, and the like, among others, are disclosed in U.S. Patent Application Publication No. 2008/0228127, published Sep. 18, 2008, the entire content of which is incorporated by reference herein.
Delivery Device for Advancing Implant Through Pre-Formed Corneal Incision
The implant delivery device 110 can be provided in a sterile packaging for single-use operation. For example, a double polythene bag may be used for sterility purposes, in combination with a blister packaging to facilitate use by the operator while still maintaining safe usage.
The delivery device 110 is generally elongate in structure, and generally comprises an outer housing and handpiece 122, an implant retainer 124 (see
The outer housing 122 encloses various componentry of the delivery device 110 and can comprise two housing portions such as a left housing portion 136a and a right housing portion 136b, which can be attached during fabrication of the delivery device 110.
Selected portions of the outer housing and handpiece 122 have ergonomic features such as the hand grip area 138a, which has a ribbed texture or the like to facilitate manual handling by a surgeon, medical operator or practitioner (a similar hand grip area may be provided on the right housing portion 136b). Various internal structures of the outer housing 122 engage the other components of the delivery device 110, as discussed further below.
The outer housing 122 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the outer housing 122 comprises a thermoplastic material such as medical grade polycarbonate that is gamma stable.
The outer housing 122 can efficaciously be dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the outer housing 122 has a length of about 5.60 inches, though other lengths may also be efficaciously utilized, for example, based on the size of the user's hand (e.g., between about 4 inches and about 8 inches or any length in between).
The implant retainer 124 (see
The insertion sleeve assembly 126 generally comprises an insertion sleeve 140 and a support member 142 fixedly attached thereto and to the outer housing 122. The insertion sleeve 140 may comprise a sleeve, tube or needle. The support member 142 may comprise a sleeve. Distal portions of the insertion sleeve 140 and support member 142 are exposed and extend beyond the distal tip of the delivery device 110 while proximal portions of the insertion sleeve 140 and support member 142 are contained within the outer housing 122. The insertion sleeve assembly 126 is discussed in further detail later herein.
The trocar assembly 128 generally comprises an obturator, or trocar, 144 and a trocar support member 146 attached thereto. The trocar support member 146 is mechanically coupled, connected or attached to the actuatable trocar trigger 130. In one embodiment, the trocar support member 146 is a clip, as illustrated in
The trocar trigger 130 generally comprises an upper finger or thumb actuatable portion 148 and a lower main body portion 150. The actuatable trigger portion 148 generally extends above the housing 122 while the main body portion 150 is generally contained within the housing 122. Before use, the trocar trigger 130 is in a forward position and, when in use, it is utilized to retract the trocar 144. The trigger main body portion 150 is mechanically coupled, connected or attached to the trocar assembly 128. The trocar trigger 130 is discussed in further detail later herein.
The trigger safety device 132 is removable and is positioned generally rearwardly with respect to the trocar trigger 130 and is mechanically coupled or engaged with the trocar trigger 130. The trigger safety device 132 prevents undesirable motion of the trocar trigger 130 during packaging, shipping and travel of the implant delivery device 110, as also discussed further below. In one embodiment, the trigger safety device 132 is a clip.
The reuse prevention structures 134a and 134b are mounted on each side of the trocar trigger 130 and within the outer housing 122. The reuse prevention structures 134a and 134b may advantageously provide a safety function to disallow reuse of the delivery device 110 so as to prevent any cross-contamination between unauthorized reuse of the single use device 110. As discussed further below, the reuse prevention structures 134a and 134b, in one embodiment, are glue blocks or preform structures that are adapted to melt, dissolve or otherwise shrink or disappear when any unapproved re-sterilization of the delivery device 110 is attempted and lock or jam the trocar trigger 130 so that its movement is thwarted. In some embodiments, a hot melt adhesive is used to freeze the trigger mechanism and prevent use after autoclave.
The implant 120 and/or the implant body 151 further comprises respective distal and proximal ribs, flanges or stops 158 and 160 which may hold the sleeve 152 in place. Moreover, the proximal structure 160 is dimensioned so that the implant cannot move rearwardly with respect to the distal end of the insertion sleeve 140. Thus, the insertion sleeve 140 can act as a backing tube to react against a proximal end of the implant 120 during removal of the implant 120 from the delivery device 110.
Advantageously, the implant 120 and/or the implant body 151 has a predetermined curvature and/or flexibility that substantially matches the curvature of the sclera and/or facilitates proper insertion in the suprachoroidal space 34. In some embodiments, the curvature of the implant 120 is configured to keep pressure on the sclera during implantation and prevent “understeer” and/or choroid penetration. In some embodiments, the curvature of implant is greater than a diameter of the eye (e.g., greater than 1 inch). The lumen 154, in accordance with certain embodiments, allows for drainage or flow of fluid (e.g., aqueous) from the anterior chamber 32 to the suprachoroidal space 34. The length of the implant 120 can range from about 1 mm to about 8 mm (e.g., 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm).
The implant 120 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the implant body 151 comprises a plastic, such as polyethersulfone (PES), and the sleeve 152 comprises a metal or alloy, such as titanium or a titanium alloy. In some embodiments, the sleeve 152 provides a visual aid in determining the proper depth of stent placement during implantation (e.g., one or more radiopaque markers).
The implant 120, in some embodiments, can also comprise a therapeutic agent or drug. For example, at least a portion of the implant 120 is coated with a therapeutic agent or drug. In one embodiment, at least the implant lumen 154 is coated with a therapeutic agent or drug, such as, but not limited to, heparin or the like.
The implant 120 can be efficaciously dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the radius of curvature R8 is about 1 inch, the diameter D8 is about at least 0.0063 inches, and the diameter D5 is about at least 340 microns. In some embodiments, the curvature is larger than the diameter of the eye (e.g., larger than 1 inch) to maintain pressure on the sclera during implantation. The implant 120 can be symmetrically designed such that it may be used in either the left or right eye. Other implants can be delivered by the delivery devices 110, 210 in addition to the implant 120.
The insertion sleeve support 142 is an elongated member through which a portion of the insertion sleeve 140 extends and is fixedly attached thereto. The insertion sleeve support 142 includes a collar 166 which mates with a corresponding portion of the outer housing 122 to fixedly attach these structures.
The insertion sleeve 140 receives a portion of the trocar 144 which passes through the sleeve lumen 162. The sleeve distal curved or non-linear portion 164 advantageously provides proper curvature and alignment of the trocar 144 and/or the implant 120 for suprachoroidal implantation.
The insertion sleeve assembly 126 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the insertion sleeve 140 and sleeve support 142 comprise a liquid crystal polymer or thermoplastic such as polycarbonate which are molded to form the assembly. In another non-limiting embodiment, the insertion sleeve 140 and sleeve support 142 comprise stainless steel and are welded (spot or continuous) to form the assembly. The insertion sleeve 140 can efficaciously comprise 26±5 gauge hypodermic tubing, as required or desired, including 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 and 31 gauge.
The insertion sleeve assembly 126 can be efficaciously dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the length L91 is about 1.8 inches, the length L92 is about 0.06 inches, the diameter D91 is about 0.018 inches, the diameter D92 is about 0.001 inches, the radius of curvature R9 is about 0.11 inches, and the angle θ9 is about 28° (degrees).
The obturator, or trocar, 144 extends through the trocar support member 146, which is configured to engage the trocar trigger 130, and be retractable on actuation of the trocar trigger 130. The curved distal portion 168 may have a predetermined curvature to allow a proper angle of attack to penetrate ocular tissue to provide access for implantation of the implant 120 in the suprachoroidal space 34. The trocar may have slight flexibility to facilitate conformance to the eye anatomy during insertion. In one embodiment, the predetermined curvature is adapted to keep pressure on the sclera during implantation and prevent or inhibit “understeer” or choroid penetration.
In some embodiments, the trocar support member 146 is configured to mechanically engage, couple, connect or fixedly attach to a recessed portion of the trocar trigger 130. Thus, actuation or retraction of the trocar trigger 130 may result in movement and retraction of the obturator, or trocar 144.
The trocar assembly 128 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the trocar 144 comprises a metal or metal alloy such as spring tempered 304 stainless steel with a predetermined flexibility and resilience, and the trocar support member 146 comprises a metal or metal alloy such as 301 stainless steel with a predetermined hardness. The trocar 144 and trocar support member 146 can be welded together, such as, denoted by weld spots 172, or otherwise attached in other suitable manners, for example molding and the like, as needed or desired.
The trocar assembly 128 can be efficaciously dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the radius of curvature R13 of the trocar distal curved portion 168 is about 1 inch (which generally conforms to the implant's radius of curvature and may prevent implant creep), the diameter D13 is about 0.006 inches (which provides a low tolerance fit within the implant's lumen), the length L13 is about 0.17 inches, the overall unbent length of the trocar 144 is about 2.3 inches, and the radius of curvature of the trocar distal end tip 170 is in the range from about 0.001 to about 0.003 inches. In various embodiments, the radius of curvature R13 of the trocar distal curved portion 168 can range from 0.4 inches to about 2.2 inches. In one embodiment, the curvature of the distal curved portion 168 is configured to be larger than the diameter of the eye (e.g., larger than 1 inch) in order to maintain pressure against the sclera during the implantation procedure.
The trigger main body portion 150 comprises a slot, cavity, opening or recessed portion 171 which mates with and attaches to a portion of the trocar support member 146 (e.g., clip) thereby effectively coupling and connecting the trocar trigger 130 and the trocar 144. The trigger main body portion 150 may also comprise multiple pins 174 disposed generally symmetrically on either side, which slidably engage the internal structure of the outer housing 122, such as the left and right slots therein (one of which slots is depicted by reference numeral 178b in
The trigger main body portion 150 further comprises slots 176 on each side that respectively receive the reuse prevention structures 134a and 134b (e.g., glue blocks) that are mounted therein. As noted above, and discussed further herein, the glue blocks can be configured to melt, dissolve, or otherwise shrink or disappear and lock the trocar trigger 130 to prevent unapproved use for the safety of the patient. Other reuse prevention mechanisms may also be used. In some embodiments, a hot melt adhesive is used to freeze the trigger mechanism and prevent use after autoclave.
The trocar trigger 130 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the trocar trigger 130 comprises a plastic or thermoplastic, such as polyethylene.
As noted earlier, the trigger safety device 132 is configured to prevent or inhibit undesirable motion of the trocar trigger 130 during packaging, shipping and travel of the implant delivery device 110. The lower portion 180 is engaged with the trocar trigger 130 prior to use of the delivery device 110 and, by manipulation of the upper portion 178, the trigger safety device 132 is removed from the delivery device 110 prior to the surgical procedure.
The trigger safety device 132 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the trigger safety device 132 comprises a thermoplastic such as a polycarbonate, for example, Makrolon® 2458.
The delivery device 110 generally comprises, but is not limited to, materials composed of stainless steel, molded plastic and silicone, among others and equivalents thereof.
Methods of Implant Delivery Through Pre-Formed Corneal Incision
In some embodiments, a cohesive viscoelastic is added to the anterior chamber, as needed, to maintain intraocular pressure for use of a gonioprism (surgeons may select a cohesive viscoelastic of their preference, including but not limited to, Healon, Amvisc or Provisc) through the incision created for implant or stent delivery or other surgery (e.g., cataract surgery).
If a gonioprism is used for visualization, the gonioprism is placed on the cornea. A surgical microscope and patient may be positioned to provide clear visualization of the trabecular meshwork on the nasal side of the eye through the gonioprism. The patient's head may be tilted as far as practical away from the surgeon, and the microscope may be tilted toward the surgeon to ensure a proper viewing angle.
In some embodiments, the anterior chamber angle is inspected using the gonioprism or other visualization member to ensure good visualization at the nasal implant location.
The implant delivery device 110 is removed from the blister tray and the implant retainer 124 is removed from the implant and trocar tip (e.g., using fine forceps) without disrupting the implant position and taking care that the implant 120 does not slide off the trocar 144.
The trigger safety device 132 may then be removed, taking care once again that the implant 120 does not slide off the trocar 144, and that the trocar trigger 130 is maintained in the forward position by the operator, and does not slide rearward.
If required, the anterior chamber can be deepened by injecting additional cohesive viscoelastic into the anterior chamber to aid in chamber maintenance. The inserter tip can be coated with a small drop of viscoelastic, as required.
In accordance with some embodiments, the implantation procedure is performed in conjunction with another ophthalmic procedure, such as cataract surgery, and as illustrated in
As illustrated in
Next, as illustrated in
In accordance with several embodiments, during implantation or insertion of the implant 120, an obturator (e.g., trocar 144) extends through the implant or stent lumen 154 to advantageously prevent tissue ingress and lumen clogging during implant insertion (e.g., prior to removal of the trocar 144 from the implant lumen 154). Moreover, advantageously, and in accordance with several embodiments, a generally rounded, and not sharp trocar or obturator tip or distal end 170 is utilized to glide smoothly down the sclera and prevent any undesirable sticking, scraping and/or attendant wound healing/fibrosis/encapsulation issues, while still being sharp enough to dissect and separate the ciliary muscle attachment in order to enter the suprachoroidal space atraumatically.
In accordance with some non-limiting embodiments, the outer diameter of the stent or implant 120 is between about 300 μm and 400 μm (e.g., 350 μm, 360 μm, 375 μm, 380 μm, 390 μm), which can advantageously avoid and/or mitigate any cyclodialysis cleft issues related with implantation. For example, in some embodiments, the delivery device 110 does not create a cyclodialysis cleft substantially larger than the implant 120 itself, and in other embodiments, does not create a cyclodialysis cleft in that the delivery device 110 and implant 120 are delivered through fibrous tissue bands of the ciliary muscle as opposed to dissecting the ciliary muscle from the sclera at the anterior chamber angle.
Next, as illustrated in
As illustrated in
In some embodiments, the operator confirms that the implant is in a proper position (e.g., the proximal end rests in the anterior chamber with an unobstructed inlet) using the operating microscope and gonioprism. The anterior chamber can be irrigated and aspirated with balanced salt solution (BSS) to remove all viscoelastic. If needed, the posterior edge of the incision is pressed down to facilitate substantially complete removal of the viscoelastic. The anterior chamber can then be inflated with saline solution to achieve physiologic pressure, as required.
In some embodiments, a predetermined curvature of both (or at least one of) the implant 120 and delivery device 110 is provided to desirably keep pressure on the sclera during implantation and prevent “understeer” or choroid penetration. The delivery device 110 can be curved to maintain the implant 120 at the same curvature during the shelf life, which desirably prevents plastic creep and thus maintains the implant's or stent's curvature specification. In one non-limiting embodiment, the curvature is larger than a diameter of the eye (e.g., larger than the 1 inch) in order to maintain the pressure on the sclera.
Delivery Device for Advancing Implant Through Device-Formed Corneal Incision
The delivery device 210 can be provided in a sterile packaging for single-use operation. For example, a double polythene bag may be used for sterility purposes, in combination with a blister packaging to facilitate use by the operator while still maintaining safe usage.
The delivery device 210 is generally elongate in structure, and generally comprises an outer housing and handpiece 222, a removable protective tube 224, a corneal penetration needle assembly 226, a trocar assembly 228, a trocar trigger 230, a pusher tube assembly 328, a pusher tube trigger 330, a trigger safety device 232 and/or two pairs of reuse prevention structures 234a, 234b and 334a, 334b.
The outer housing 222 is similar to the outer housing 122 and encloses various componentry of the delivery device 210 and can comprise two housing portions such as a left housing portion 236a and a right housing portion 236b, which are attached during fabrication of the delivery device 210.
Selected portions of the outer housing 222 have ergonomic features such as the hand grip area 238a which has a ribbed texture or the like to facilitate manual handling by a surgeon, medical operator or practitioner (a similar hand grip area is provided on the right housing portion 236b). Various internal structures of the outer housing 222 engage the other components of the delivery device 210, as discussed further below.
The outer housing 222 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the outer housing 222 comprises a thermoplastic material, such as medical grade polycarbonate that is gamma stable.
The outer housing 222 can efficaciously dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the outer housing 222 has a length of about 5.60 inches, though other lengths may also be efficaciously utilized, for example, based on the size of the user's hand (e.g., from about 4 inches to about 8 inches and any length in between).
The protective cover tube 224 may be removably mounted on a portion of the corneal penetration needle assembly 226 that extends beyond a distal end of the outer housing 222. The protective cover tube 224 may be removed before the delivery device 210 is used. One purpose of the protective cover tube 224 may be to protect the corneal penetration needle assembly 226 and the components therein during packaging, shipping and travel of the implant delivery device 210.
The protective cover tube 224 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the protective cover tube 224 comprises a thermoplastic, such as low density polyethylene (LDPE).
The corneal penetration needle assembly 226 generally comprises a corneal penetration needle 240 and a support member 242 (e.g., sleeve) fixedly attached thereto and to the outer housing 222. Optionally, a seal 243 is provided to further protect the inner componentry of the delivery device 210 from undesirable fluid entrance. Distal portions of the corneal penetration needle 240 and support member 242 may be exposed and extend beyond the distal tip of the delivery device 210, while proximal portions of the corneal penetration needle 240 and support member 242 may be contained within the outer housing 222. Portions of the needle 240 may comprise a hydrophilic or hydrophobic coating. The corneal penetration needle assembly 226 is discussed in further detail later herein.
The trocar assembly 228 generally comprises an obturator, or trocar 244 and a trocar support member 246 (e.g., collar) fixedly attached thereto. The trocar support member 246 is mechanically coupled, connected or attached to the actuatable trocar trigger 230. A substantial distal portion of the trocar 244 extends through the corneal penetration needle 240 (and pusher tube) with a distal end portion also extending through the implant 220. A proximal portion of the trocar 244 and the trocar support member 246 are contained within the outer housing 222. The trocar assembly 228 is discussed in further detail later herein.
The trocar trigger 230 generally comprises an upper finger or thumb actuatable portion 248 and a lower main body portion 250. The actuatable trigger portion 248 generally extends outside the outer housing 222 while the main body portion 250 is generally contained within the outer housing 222. Before use, the trocar trigger 230 is in a rear position and, when in use, it is utilized to first advance and then retract the trocar 244. The trigger main body portion 250 is mechanically coupled, connected or attached to the trocar assembly 228. The trocar trigger 230 is also mechanically and/or operatively coupled to the pusher tube trigger 330. The trocar trigger 230 is discussed in further detail later herein.
The pusher tube assembly 328 generally comprises a pusher tube 344 and a pusher tube collar 346 fixedly attached thereto. The pusher tube collar 346 is mechanically coupled, connected or attached to the actuable pusher tube trigger 330. A substantial portion of the distal portion of the pusher tube 344 extends through the insertion needle 340, with a distal end being positioned proximal of the implant 220. A proximal portion of the pusher tube 344 and the pusher tube collar 346 are contained within the outer housing 222. The pusher tube assembly 328 is discussed in further detail later herein.
The pusher tube trigger 330 generally comprises an upper portion 348 distally proximate to the upper finger or thumb actuable trocar trigger portion 248 and a lower main body portion 350. The upper portion 348 generally extends outside the housing 222 while the main body portion 350 is generally contained within the housing 222. Before use, the pusher tube trigger 330 is in a rear position and, when in use, it is utilized to advance the pusher tube 344 (and the implant 220). The trigger main body portion 350 is mechanically coupled, connected or attached to the pusher tube device 328. The pusher tube trigger 330 is also mechanically and/or operatively coupled to the trocar trigger 230. The pusher tube trigger 330 is discussed in further detail later herein.
The trigger safety member 232 (e.g., clip) may be removable and positioned generally forwardly with respect to the pusher tube trigger 330. The trigger safety member 232 is mechanically coupled or engaged with the pusher tube trigger 330. In some embodiments, the trigger safety member 232 inhibits undesirable motion of the pusher tube trigger 330 and the trocar trigger 230 during packaging, shipping and travel of the implant delivery device 210. The trigger safety member 232 may be substantially the same in structure as the trigger safety device 132 discussed above.
The reuse prevention structures 234a, 234b and 334a, 334b may be mounted on each side of the trocar trigger 230 and the pusher tube trigger 330 respectively, and within the outer housing 222. The reuse prevention structures 234a, 234b and 334a, 334b advantageously provide a safety function to disallow reuse of the delivery device 210 so as to prevent any cross-contamination between unauthorized reuse of the single use device 210. In some embodiments, the reuse prevention structures 234a, 234b and 334a, 334b comprise glue blocks or preforms that are adapted to melt or dissolve when any unapproved re-sterilization of the delivery device 210 is attempted and lock or jam the trocar trigger 230 and the pusher tube trigger 330 so that their movement is thwarted. In some embodiments, a hot melt adhesive is used to freeze the trigger mechanism and prevent use after autoclave.
The implant 220 has an implant body 251 with a proximal sleeve 252 and is located within a distal end portion of the insertion needle 240 when the delivery device 210 is loaded with the implant prior to packaging and storage or before use. The implant 220 is substantially the same in structure as the implant 120 discussed above.
The insertion needle support 242 is an elongated member through which a portion of the needle 240 extends and is attached thereto. The insertion needle support 242 may include a collar 266 that mates with a corresponding portion of the outer housing 222 to fixedly attach these structures.
A seal 243 is mounted on a proximal end portion of the insertion needle 240. The seal 243 may advantageously protect the inner componentry of the delivery device 210 from undesirable fluid entrance and may engage an internal structure of the delivery device 210 and/or housing 222. The insertion or corneal penetration needle 240 may comprise a hydrophilic or hydrophobic coating along at least a portion of its length.
The insertion needle 240 receives a portion of the pusher tube 344 that passes through the needle lumen 262 and contains the preloaded implant 220 distal of the pusher tube 344, which in turn receives a portion of the trocar 244. The needle distal curved or non-linear portion 264 advantageously provides proper curvature and alignment of the trocar 244 and the implant 220 for suprachoroidal implantation.
The insertion needle assembly 226 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the insertion sleeve 240 and support member 242 comprise stainless steel and are welded (spot or continuous) to form the assembly, and the seal 243 can comprise silicone or the like. The insertion or corneal penetration needle 240 can efficaciously comprise 25±5 gauge hypodermic tubing, as required or desired, including, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30 gauge.
The insertion needle assembly 226 can efficaciously be dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the length L251 is about 1.22 inches, the curved length L252 is about 0.3 inches, the diameter D25 is about 0.02 inches, the radius of curvature R25 is about 1 inch, and the width W26 is about 0.031 inches. The radius of curvature R25 can have the same or substantially the same radius of curvature as the trocar 244. In some embodiments, the curvature of the insertion needle assembly 226 is adapted to be larger than a diameter of the eye (e.g., greater than 1 inch) to, for example, maintain pressure on the sclera during a delivery or implantation procedure.
The trocar 244 extends through the trocar support member 246, which is configured to engage the trocar trigger 230, and be advanceable and retractable on actuation of the trigger 230. The curved distal portion 268 has a predetermined curvature to allow a proper angle of attack to penetrate ocular tissue to provide access for implantation of the implant 220 in the suprachoroidal space 34.
More particularly, a collar portion 247 of the trocar support member 246 is mechanically engaged, coupled, connected or fixedly attached to a recessed portion of the trocar trigger 230. Thus, actuation, advancement or retraction of the trocar trigger 230 results in movement, advancement and retraction of the trocar 244.
The trocar assembly 228 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the trocar 244 comprises a metal or metal alloy such as spring tempered 304 stainless steel with a predetermined flexibility and resilience, and the trocar support member 246 comprises a metal or metal alloy such as 303 stainless steel with predetermined properties. The trocar 244 and trocar support member 246 (e.g., collar) can be welded together (spot or continuous welding), or otherwise attached in other suitable manners, for example molding and the like, as needed or desired.
The trocar assembly 228 can efficaciously be dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the radius of curvature R32 of the trocar distal curved portion 268 is about 1 inch (which generally conforms to the needle's, pusher tube's and implant's radius of curvature and prevents implant creep and disorientation), the diameter D32 is about 0.006 inches (which provides a low tolerance fit within the implant's lumen), the curved length L321 is about 0.67 inches, the length L322 is about 2.1 inches, the overall unbent length of the trocar 244 is about 3.15 inches, the radius of curvature of the trocar distal end tip 270 is in the range from about 0.001 to about 0.003 inches, and the dimension R32 is about 0.22 inches. In various embodiments, the radius of curvature R32 of the trocar distal curved portion 268 can range from 0.4 inches to about 2.2 inches. In some embodiments, the curvature of the distal curved portion 268 is adapted be slightly larger than a diameter of the eye (e.g., larger than 1 inch) to, for example, maintain pressure on the sclera during the delivery or implantation procedure. It should be appreciated, that the above non-limiting dimensions can involve that at least the trocar dimensions H32, R32 and/or L321 (or other related dimensions) can reflect an after “bend” manufacturing or fabrication process or step that has been performed or implemented on the trocar 244.
The trigger body portion 250 comprises a slot, cavity, opening or recessed portion 271 which mates with and attaches to a portion of the trocar collar portion 247 thereby effectively coupling and connecting the trigger 230 and the trocar 244. The trigger body portion 250 may also comprise multiple pins 274 disposed generally symmetrically on either side which slidably engage the internal structure of the housing 222 such as the left and right slots therein, one of which slots is depicted by reference numeral 278b in
The trigger body portion 250 may further comprise slots 276 on each side which respectively receive the reuse prevention structures 234a and 234b that are mounted therein. The reuse prevention structures (e.g., glue blocks or preforms) may be configured to melt or otherwise dissolve or degrade and lock the trocar trigger 230 to prevent unapproved use for the safety of the patient. In some embodiments, a hot melt adhesive is used to freeze the trigger mechanism and prevent use after autoclave.
The trocar trigger 230 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the trocar trigger 230 comprises a plastic or thermoplastic, such as polyethylene.
The pusher tube 344 extends from the pusher tube support member 346 that is configured to engage the pusher tube trigger 330, and be advanceable on actuation of the trigger 330, and desirably be lockable thereafter, in some embodiments. The curved distal portion 368 may have a predetermined curvature to allow a proper angle of attack for the trocar 244 to penetrate ocular tissue to provide access for implantation of the implant 220 in the suprachoroidal space 34. The predetermined curvature may be configured to match the curvature of the sclera.
More particularly, a collar portion 347 of the pusher tube collar 346 mechanically engages, couples, connects or fixedly attaches to a recessed portion of the pusher tube trigger 330. Thus, actuation and advancement of the pusher tube trigger 330 results in movement and advancement of the pusher tube 344.
The pusher tube assembly 328 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the pusher tube 344 comprises nitinol tubing, and the pusher tube collar 346 comprises nitinol bar stock. The pusher tube 344 and collar 346 can be welded together (spot or continuous welding), or otherwise attached in other suitable manners, for example molding and the like, as needed or desired.
The pusher tube assembly 328 can efficaciously be dimensioned in various suitable manners, as required or desired. In one non-limiting embodiment, the radius of curvature R35 of the pusher tube distal curved portion 368 is about 1 inch (which generally conforms to the needle's, trocar's and implant's radius of curvature and prevents implant creep and disorientation), the diameter D35 is about 0.014 inches (which provides a low tolerance fit within the needle's lumen), the curved length L351 is about 0.5 inches, the length L352 is about 2.1 inches, and the overall unbent length of the pusher tube 344 is about 2.57 inches. In various embodiments, the radius of curvature R35 of the pusher tube distal curved portion 368 can range from 0.4 inches to about 2.2 inches. In some embodiments, the curvature of the pusher tube distal curved portion 368 is adapted to be slightly larger than a diameter of an eye (e.g., greater than 1 inch), for example, maintain pressure on the sclera during the delivery or implantation procedure. It should be appreciated, that the above non-limiting dimensions can involve that at least the pusher tube dimensions L351 and/or R35 (or other related dimensions) can reflect an after “bend” manufacturing or fabrication process or step that has been performed or implemented on the pusher tube 344.
The trigger main body portion 350 may comprise a slot, cavity, opening or recessed portion 371 that mates with and attaches to a portion of the pusher tube collar portion 347, thereby effectively coupling and connecting the trigger 330 and the pusher tube 344. The trigger body portion 350 may also comprise multiple pins 374 disposed generally symmetrically on either side that slidably engage the internal structure of the housing 222 such as the left and right slots therein (one of which slots is depicted by reference numeral 278b in
The trigger main body portion 350 may further comprise slots 376 on each side which respectively receive the reuse prevention structures 334a and 334b that are mounted therein. The reuse prevention structures 334a and 334b are adapted to prevent unapproved use for the safety of the patient.
The pusher tube trigger 330 can efficaciously be fabricated from various suitable materials, as required or desired. In one non-limiting embodiment, the pusher tube trigger 330 comprises a plastic or thermoplastic such as polyethylene.
The delivery device 210 generally comprises, but is not limited to, materials composed of stainless steel, molded plastic and nitinol, among others and equivalents thereof.
Methods of Implant Delivery Through Device-Formed Corneal Incision
In some embodiments, a surgical microscope and the patient are positioned to provide a substantially clear visualization of the trabecular meshwork through a gonioprism on the nasal side of the eye. The patient's head can be tilted as far as practical from the surgeon, and the microscope can be tilted toward the surgeon to ensure a proper viewing angle.
The delivery device 210 is removed from its package. The protective cover tube 224 is carefully removed from the insertion needle and the safety member 232 holding the triggers is removed by the operator taking care that the triggers 230 and 330 are maintained in the rear position.
If a gonioprism is used, the gonioprism is placed on the cornea, and the anterior chamber angle is inspected using the gonioprism to ensure a good visualization at the nasal implant location. The gonioprism is then removed. Other visualization devices may be used or the procedure may be performed without use of a visualization device.
As illustrated in
Next, as illustrated in
In accordance with several embodiments, during implantation or insertion of the implant 220 the trocar, or obturator, 244 extends through the implant or stent lumen 154 to advantageously prevent tissue ingress and lumen clogging during implant insertion (prior to removal of the trocar, or obturator, 244 from the implant lumen 154).
Next, as illustrated in
As illustrated in
In some embodiments, the operator confirms that the implant is in a proper position (e.g., the proximal end rests in the anterior chamber with an unobstructed inlet) using the operating microscope and gonioprism. The anterior chamber can be irrigated and aspirated with balanced salt solution (BSS) to remove all viscoelastic, if used. If needed, the posterior edge of the incision is pressed down to facilitate substantially complete removal of the viscoelastic, if used. The anterior chamber can then be inflated with saline solution to achieve physiologic pressure, as required.
In some embodiments, a predetermined curvature of both (or at least one of) the implant or stent 220 and delivery device 210 is provided to desirably keep pressure on the sclera during implantation and prevent “understeer” or choroid penetration. The delivery device 210 can be curved to maintain the implant or stent 220 at the same curvature during the shelf life which desirably prevents plastic creep and thus maintain the implant's or stent's curvature specification. In one non-limiting embodiment, the curvature is larger than a diameter of the eye (e.g., larger than a 1 inch diameter) in order to maintain the pressure on the sclera.
In some embodiments, the pusher tube 344 is configured to react against a proximal end of the implant or stent 220 during trocar or obturator removal. Advantageously, the “lazy” curve or curvature of the needle 240 and/or substantially the entire system 210 (see, e.g.,
Moreover, in accordance with some embodiments, the needle 240 advantageously traverses across the eye (finite height anterior chamber clearance) without contacting the iris or cornea. In some embodiments, the implant or stent 220 is maintained at its specified, predetermined or required or desired curvature throughout substantially its shelf life, for example, to prevent plastic creep.
Drugs and Therapeutic Agents
In some embodiments, the implants disclosed herein can provide for delivery of a therapeutic agent or drug. The therapeutic agent can be, for example, an intraocular pressure-lowering drug. In some embodiments, the therapeutic agent or drug is introduced concurrently with the delivery of the shunt to the eye. The therapeutic agent or drug can be part of the implant itself. For example, the therapeutic agent or drug can be embedded in the material of the shunt, or coat at least a portion of the implant. The therapeutic agent or drug may be present on various portions of the implant. For example, the therapeutic agent or drug may be present on the distal end of the implant, or the proximal end of the implant. The implant can include combination of therapeutic agents or drugs. The different therapeutic agents or drugs can be separated or combined. One kind of therapeutic agent or drug can be present at the proximal end of the implant, and a different kind of therapeutic agent or drug can be present at the distal end of the implant. For example, an anti-proliferative agent may be present at the distal end of the implant to prevent growth, and a growth-promoting agent may be applied to the proximal end of the implant to promote growth.
Examples of drugs may include various anti-secretory agents; antimitotics and other anti-proliferative agents, including among others, anti-angiogenesis agents such as angiostatin, anecortave acetate, thrombospondin, VEGF receptor tyrosine kinase inhibitors and anti-vascular endothelial growth factor (anti-VEGF) drugs such as ranibizumab (LUCENTIS®) and bevacizumab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib and sorafenib and any of a variety of known small-molecule and transcription inhibitors having anti-angiogenesis effect (additional non-limiting examples of such anti-VEGF compounds are described in Appendix A, which is attached herewith and made a part of this application); classes of known ophthalmic drugs, including: glaucoma agents, such as adrenergic antagonists, including for example, beta-blocker agents such as atenolol, propranolol, metipranolol, betaxolol, carteolol, levobetaxolol, levobunolol and timolol; adrenergic agonists or sympathomimetic agents such as epinephrine, dipivefrin, clonidine, aparclonidine, and brimonidine; parasympathomimetics or cholingeric agonists such as pilocarpine, carbachol, phospholine iodine, and physostigmine, salicylate, acetylcholine chloride, eserine, diisopropyl fluorophosphate, demecarium bromide); muscarinics; carbonic anhydrase inhibitor agents, including topical and/or systemic agents, for example acetozolamide, brinzolamide, dorzolamide and methazolamide, ethoxzolamide, diamox, and dichlorphenamide; mydriatic-cycloplegic agents such as atropine, cyclopentolate, succinylcholine, homatropine, phenylephrine, scopolamine and tropicamide; prostaglandins such as prostaglandin F2 alpha, antiprostaglandins, prostaglandin precursors, or prostaglandin analog agents such as bimatoprost, latanoprost, travoprost and unoprostone.
Other examples of drugs may also include anti-inflammatory agents including for example glucocorticoids and corticosteroids such as betamethasone, cortisone, dexamethasone, dexamethasone 21-phosphate, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, prednisolone, fluorometholone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, beclomethasone, budesonide, flunisolide, fluticasone, hydrocortisone, hydrocortisone acetate, loteprednol, rimexolone and non-steroidal anti-inflammatory agents including, for example, diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, and ketorolac, salicylate, indomethacin, ibuprofen, naxopren, piroxicam and nabumetone; anti-infective or antimicrobial agents such as antibiotics including, for example, tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodium propionate, aminoglycosides such as gentamicin and tobramycin; fluoroquinolones such as ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin; bacitracin, erythromycin, fusidic acid, neomycin, polymyxin B, gramicidin, trimethoprim and sulfacetamide; antifungals such as amphotericin B and miconazole; antivirals such as idoxuridine trifluorothymidine, acyclovir, gancyclovir, interferon; antimicotics; immune-modulating agents such as antiallergenics, including, for example, sodium chromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine, pyrilamine, prophenpyridamine; anti-histamine agents such as azelastine, emedastine and levocabastine; immunological drugs (such as vaccines and immune stimulants); MAST cell stabilizer agents such as cromolyn sodium, ketotifen, lodoxamide, nedocrimil, olopatadine and pemirolastciliary body ablative agents, such as gentimicin and cidofovir; and other ophthalmic agents such as verteporfin, proparacaine, tetracaine, cyclosporine and pilocarpine; inhibitors of cell-surface glycoprotein receptors; decongestants such as phenylephrine, naphazoline, tetrahydrazoline; lipids or hypotensive lipids; dopaminergic agonists and/or antagonists such as quinpirole, fenoldopam, and ibopamine; vasospasm inhibitors; vasodilators; antihypertensive agents; angiotensin converting enzyme (ACE) inhibitors; angiotensin-1 receptor antagonists such as olmesartan; microtubule inhibitors; molecular motor (dynein and/or kinesin) inhibitors; actin cytoskeleton regulatory agents such as cyctchalasin, latrunculin, swinholide A, ethacrynic acid, H-7, and Rho-kinase (ROCK) inhibitors; remodeling inhibitors; modulators of the extracellular matrix such as tert-butylhydro-quinolone and AL-3037A; adenosine receptor agonists and/or antagonists such as N-6-cylclophexyladenosine and (R)-phenylisopropyladenosine; serotonin agonists; hormonal agents such as estrogens, estradiol, progestational hormones, progesterone, insulin, calcitonin, parathyroid hormone, peptide and vasopressin hypothalamus releasing factor; growth factor antagonists or growth factors, including, for example, epidermal growth factor, fibroblast growth factor, platelet derived growth factor or antagonists thereof, transforming growth factor beta, somatotrapin, fibronectin, connective tissue growth factor, bone morphogenic proteins (BMPs); cytokines such as interleukins, CD44, cochlin, and serum amyloids, such as serum amyloid A.
Other therapeutic agents may include neuroprotective agents such as lubezole, nimodipine and related compounds, and including blood flow enhancers such as dorzolamide or betaxolol; compounds that promote blood oxygenation such as erythropoeitin; sodium channels blockers; calcium channel blockers such as nilvadipine or lomerizine; glutamate inhibitors such as memantine nitromemantine, riluzole, dextromethorphan or agmatine; acetylcholinsterase inhibitors such as galantamine; hydroxylamines or derivatives thereof, such as the water soluble hydroxylamine derivative OT-440; synaptic modulators such as hydrogen sulfide compounds containing flavonoid glycosides and/or terpenoids, such as Ginkgo biloba; neurotrophic factors such as glial cell-line derived neutrophic factor, brain derived neurotrophic factor; cytokines of the IL-6 family of proteins such as ciliary neurotrophic factor or leukemia inhibitory factor; compounds or factors that affect nitric oxide levels, such as nitric oxide, nitroglycerin, or nitric oxide synthase inhibitors; cannabinoid receptor agonsists such as WIN55-212-2; free radical scavengers such as methoxypolyethylene glycol thioester (MPDTE) or methoxypolyethlene glycol thiol coupled with EDTA methyl triester (MPSEDE); anti-oxidants such as astaxathin, dithiolethione, vitamin E, or metallocorroles (e.g., iron, manganese or gallium corroles); compounds or factors involved in oxygen homeostasis such as neuroglobin or cytoglobin; inhibitors or factors that impact mitochondrial division or fission, such as Mdivi-1 (a selective inhibitor of dynamin related protein 1 (Drp1)); kinase inhibitors or modulators such as the Rho-kinase inhibitor H-1152 or the tyrosine kinase inhibitor AG1478; compounds or factors that affect integrin function, such as the Beta 1-integrin activating antibody HUTS-21; N-acyl-ethanaolamines and their precursors, N-acyl-ethanolamine phospholipids; stimulators of glucagon-like peptide 1 receptors (e.g., glucagon-like peptide 1); polyphenol containing compounds such as resveratrol; chelating compounds; apoptosis-related protease inhibitors; compounds that reduce new protein synthesis; radiotherapeutic agents; photodynamic therapy agents; gene therapy agents; genetic modulators; auto-immune modulators that prevent damage to nerves or portions of nerves (e.g., demyelination) such as glatimir; myelin inhibitors such as anti-NgR Blocking Protein, NgR(310)ecto-Fc; other immune modulators such as FK506 binding proteins (e.g., FKBP51); and dry eye medications such as cyclosporine A, delmulcents, and sodium hyaluronate.
Other therapeutic agents that may be used include: other beta-blocker agents such as acebutolol, atenolol, bisoprolol, carvedilol, asmolol, labetalol, nadolol, penbutolol, and pindolol; other corticosteroidal and non-steroidal anti-inflammatory agents such aspirin, betamethasone, cortisone, diflunisal, etodolac, fenoprofen, fludrocortisone, flurbiprofen, hydrocortisone, ibuprofen, indomethacine, ketoprofen, meclofenamate, mefenamic acid, meloxicam, methylprednisolone, nabumetone, naproxen, oxaprozin, prednisolone, prioxicam, salsalate, sulindac and tolmetin; COX-2 inhibitors like celecoxib, rofecoxib and. Valdecoxib; other immune-modulating agents such as aldesleukin, adalimumab (HUMIRA®), azathioprine, basiliximab, daclizumab, etanercept (ENBREL®), hydroxychloroquine, infliximab (REMICADE®), leflunomide, methotrexate, mycophenolate mofetil, and sulfasalazine; other anti-histamine agents such as loratadine, desloratadine, cetirizine, diphenhydramine, chlorpheniramine, dexchlorpheniramine, clemastine, cyproheptadine, fexofenadine, hydroxyzine and promethazine; other anti-infective agents such as aminoglycosides such as amikacin and streptomycin; anti-fungal agents such as amphotericin B, caspofungin, clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine and nystatin; anti-malarial agents such as chloroquine, atovaquone, mefloquine, primaquine, quinidine and quinine; anti-mycobacterium agents such as ethambutol, isoniazid, pyrazinamide, rifampin and rifabutin; anti-parasitic agents such as albendazole, mebendazole, thiobendazole, metronidazole, pyrantel, atovaquone, iodoquinaol, ivermectin, paromycin, praziquantel, and trimatrexate; other anti-viral agents, including anti-CMV or anti-herpetic agents such as acyclovir, cidofovir, famciclovir, gangciclovir, valacyclovir, valganciclovir, vidarabine, trifluridine and foscarnet; protease inhibitors such as ritonavir, saquinavir, lopinavir, indinavir, atazanavir, amprenavir and nelfinavir; nucleotide/nucleoside/non-nucleoside reverse transcriptase inhibitors such as abacavir, ddI, 3TC, d4T, ddC, tenofovir and emtricitabine, delavirdine, efavirenz and nevirapine; other anti-viral agents such as interferons, ribavirin and trifluridiene; other anti-bacterial agents, including cabapenems like ertapenem, imipenem and meropenem; cephalosporins such as cefadroxil, cefazolin, cefdinir, cefditoren, cephalexin, cefaclor, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, cefpodoxime, cefprozil, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime and loracarbef; other macrolides and ketolides such as azithromycin, clarithromycin, dirithromycin and telithromycin; penicillins (with and without clavulanate) including amoxicillin, ampicillin, pivampicillin, dicloxacillin, nafcillin, oxacillin, piperacillin, and ticarcillin; tetracyclines such as doxycycline, minocycline and tetracycline; other anti-bacterials such as aztreonam, chloramphenicol, clindamycin, linezolid, nitrofurantoin and vancomycin; alpha blocker agents such as doxazosin, prazosin and terazosin; calcium-channel blockers such as amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil; other anti-hypertensive agents such as clonidine, diazoxide, fenoldopan, hydralazine, minoxidil, nitroprusside, phenoxybenzamine, epoprostenol, tolazoline, treprostinil and nitrate-based agents; anti-coagulant agents, including heparins and heparinoids such as heparin, dalteparin, enoxaparin, tinzaparin and fondaparinux; other anti-coagulant agents such as hirudin, aprotinin, argatroban, bivalirudin, desirudin, lepirudin, warfarin and ximelagatran; anti-platelet agents such as abciximab, clopidogrel, dipyridamole, optifibatide, ticlopidine and tirofiban; prostaglandin PDE-5 inhibitors and other prostaglandin agents such as alprostadil, carboprost, sildenafil, tadalafil and vardenafil; thrombin inhibitors; antithrombogenic agents; anti-platelet aggregating agents; thrombolytic agents and/or fibrinolytic agents such as alteplase, anistreplase, reteplase, streptokinase, tenecteplase and urokinase; anti-proliferative agents such as sirolimus, tacrolimus, everolimus, zotarolimus, paclitaxel and mycophenolic acid; hormonal-related agents including levothyroxine, fluoxymestrone, methyltestosterone, nandrolone, oxandrolone, testosterone, estradiol, estrone, estropipate, clomiphene, gonadotropins, hydroxyprogesterone, levonorgestrel, medroxyprogesterone, megestrol, mifepristone, norethindrone, oxytocin, progesterone, raloxifene and tamoxifen; anti-neoplastic agents, including alkylating agents such as carmustine lomustine, melphalan, cisplatin, fluorouracil3, and procarbazine antibiotic-like agents such as bleomycin, daunorubicin, doxorubicin, idarubicin, mitomycin and plicamycin; anti proliferative agents (such as 1,3-cis retinoic acid, 5-fluorouracil, taxol, rapamycin, mitomycin C and cisplatin); antimetabolite agents such as cytarabine, fludarabine, hydroxyurea, mercaptopurine and 5-fluorouracil (5-FU); immune modulating agents such as aldesleukin, imatinib, rituximab and tositumomab; mitotic inhibitors docetaxel, etoposide, vinblastine and vincristine; radioactive agents such as strontium-89; and other anti-neoplastic agents such as irinotecan, topotecan and mitotane.
In some embodiments, the therapeutic agent is delivered through the implant to the desired location in the eye, such as the suprachoroidal space of the uveoscleral outflow pathway. In some embodiments, the therapeutic agent is delivered to the suprachoroidal space of the uveoscleral outflow pathway in combination with a therapeutic agent delivered via trans pars plana vitrectomy, thereby delivering a therapeutic agent to both sides of the retina. In some embodiments, the implant can improve access of topical medication to the posterior uvea. In some embodiments, the implant is used to deliver a topical medication to treat a chorio-retinal disease.
In some embodiments, the delivery device 110 provides implantation through a preformed or prior corneal incision while the delivery device 210 does so through a self-created and self-sealing incision such that a “closed chamber” operation is performed.
The delivery device 110 is configured, in some embodiments, so that the implant is supported on a trocar wire or obturator in an exposed configuration. In some embodiments, the delivery device 210 supports the implant on a trocar wire or obturator within an insertion or corneal penetration needle.
In some embodiments, the delivery device 110 comprises a silicone retainer to hold the implant in place during travel. The delivery device 210, in some embodiments, incorporates a curved delivery system that provides adequate side loads and friction to hold the implant in place during travel and shipping.
The delivery device 110, in certain embodiments, employs a single trigger operation to release the implant. The delivery device 210, in accordance with some embodiments, utilizes a dual trigger operation to expose and release the implant—trocar and implant pusher tube triggers. Once the insertion needle penetrates the cornea, both triggers advance to expose the implant or stent and the trocar and obturator. The front pusher tube trigger locks the pusher tube in a forward position, thereby preventing the implant or stent from retracting back into the needle. After implant or stent implantation, the rear trocar trigger is retracted to retract the trocar and release the implant or stent.
It should be appreciated, in accordance with some embodiments, that the disclosed implant is prevented from backward movement based advantageously on the delivery device configuration. For example, the implant 120 is prevented from backward movement because of the insertion sleeve's distal end relative dimensioning and the implant 220 is prevented from backward movement because of pusher tube's distal end relative dimensioning.
Moreover, because of the material properties of the disclosed trocars, creep during shelf life should advantageously not be an issue of concern. Also, in accordance with some embodiments, given that the implants and trocars are asymmetrically curved, this orientation as packaged, prevents any undesirable rotation of the implants with respect to the trocars even when in use. Furthermore, in accordance with some embodiments, at least the implants and trocars have predetermined curvatures which, because of their selected flexibility, can conform to the particular space or ocular location they are inserted or advanced into.
In some embodiments, the delivery device 110 is configured for use in combination with another ocular surgery, such as cataract surgery. The delivery device 110 can include a preloaded implant 120 and have a pre-curved tip. The device 110 advantageously may have an ergonomic handpiece.
In some embodiments, the delivery device 210 is configured for stand-alone, in-office surgery without being performed in conjunction with other ocular surgery (e.g., cataract surgery). The delivery device 210 can include a preloaded implant 220 and can have a pre-curved tip. Also, in some embodiments, the device 210 has integrated corneal penetration and closed chamber capability so as to perform the procedure through a self-sealing incision. The device 210 may advantageously include an ergonomic handpiece. Preloading the implant 220 on the delivery instrument 210 may reduce loading errors and contribute to ease of use.
Certain embodiments provide for the implant, trocar and/or the pusher tube to flex and allow for the implant to conform to the anatomy of the suprachoroidal space.
The delivery device geometries, such as with respect to the attack angle and curvature, can advantageously ensure proper placement of the implant in the suprachoroidal space, supraciliary space, or other anatomical space.
In some embodiments, the low friction (e.g., polyethylene on polycarbonate) trigger operation, in accordance with some embodiments, advantageously allows for smooth operation during the delivery procedures. The safety members (e.g., safety clips) may advantageously prevent undesirable trigger motion during shipment and transportation of the delivery devices.
Embodiments of the trocar or obturator material and tip shape provide several advantages which include: use of high temper stainless spring steel; pointed enough tip to pierce ciliary muscle attachment; rounded enough tip to prevent irritation/tissue damage in suprachoroidal space at sclera/choroid; material and shape allows constant force against sclera during advancement in order to assure proper placement of implant within suprachoroidal space; and trocar curvature generally matches implant or stent shape to prevent plastic creep during shelf life. Moreover, advantageously, and in accordance with some embodiments, a generally rounded, and not sharp trocar or obturator tip or distal end, e.g. 170 or 270, is utilized to glide smoothly down the sclera and prevent any undesirable sticking, scraping and attendant wound healing/fibrosis/encapsulation issues, while still being sharp enough to dissect and separate the ciliary muscle attachment in order to enter the suprachoroidal space atraumatically.
Also, in accordance with some non-limiting embodiments, the outer diameter of the stent or implant 220 is between about 300 μm and 400 μm (e.g., 350 μm, 360 μm, 375 μm, 380 μm, 390 μm), which can advantageously avoid and/or mitigate any cyclodialysis cleft issues related with implantation. For example, in some embodiments, the delivery device 210 does not create a cyclodialysis cleft substantially larger than the implant 220 itself, and in other embodiments, does not create a cyclodialysis cleft in that the delivery device 210 and implant 220 are delivered through fibrous tissue bands of the ciliary muscle as opposed to dissecting the ciliary muscle from the sclera at the anterior chamber angle.
With respect to embodiments of the delivery device 210, the curved, flared and coated stainless steel insertion or corneal penetration needle is advantageously shaped to fit anatomically within eye the and avoid iris touch. Also, the tight corneal incision can minimize fluid loss from the eye by forming a substantially closed chamber self-sealing entry. Moreover, the lowered sliding friction of the needle shaft once in the eye may advantageously prevent movement during this delicate surgery, and any resultant loss of view during any interoperative gonioscopy.
In some embodiments, and once again with respect to embodiments of the delivery device 210, the superelastic nitinol pusher tube provides backup support for the implant or stent during implantation, and allows minimal sliding force during trigger operation. Also, in accordance with some embodiments, the polyethylene protective tube prevents damage to the needle tip during shipment.
The delivery device 210, in accordance with some embodiments, can advantageously be used in a “closed chamber” procedure, which may have one or more of the following advantages: no viscoelastic is required to inflate the anterior chamber; there is minimal loss of fluid from anterior chamber (this reduces chance of hypotony); no separate blade is required to form the corneal incision; results in faster surgery; there is only one time entry into the eye; a safer procedure with less chance or lowered probability for adverse event (e.g., endophthalmitis); and less expensive and more cost effective.
The curved insertion needle, trocar or obturator, and pusher tube of the delivery device 210 also, in certain embodiments allows for retention of the implant or stent shape during its entire shelf life (including during shipping) to prevent creep (such as, loss of implant or stent curvature). Moreover, the closed-chamber procedure can allow for enhanced surgical safety in a non-deepened anterior chamber by substantially matching the curvature of the cornea and allowing traversing of the eye in an ab interno procedure.
Conditional language, for example, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and/or steps.
Methods
The methods which are described and illustrated herein are not limited to the sequence of acts described, nor are they necessarily limited to the practice of all of the acts set forth. Other sequences of acts, or less than all of the acts, or simultaneous occurrence of the acts, may be utilized in practicing embodiments of the invention(s). The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “forming an incision” include “instructing the formation of an incision.”
Ranges
The ranges disclosed herein encompass any and all overlap, sub-ranges, and combinations thereof, as well as individual numerical values within that range. For example, description of a range such as from about 5 to about 30 degrees should be considered to have specifically disclosed subranges such as from 5 to 10 degrees, from 10 to 20 degrees, from 5 to 25 degrees, from 15 to 30 degrees etc., as well as individual numbers within that range, for example, 5, 10, 15, 20, 25, 12, 15.5 and any whole and partial increments therebetween. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers. For example, “about 10%” includes “10%.” For example, the terms “approximately”, “about”, and “substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result.
From the foregoing description, it will be appreciated that a novel approach for intraocular pressure control has been disclosed. While the components, techniques and aspects of embodiments of the invention have been described with a certain degree of particularity, it is manifest that many changes may be made in the specific designs, constructions and methodology herein above described without departing from the spirit and scope of this disclosure.
While a number of preferred embodiments of the invention and variations thereof have been described in detail, other modifications and methods of using and medical, diagnostic, research and therapeutic applications for the same will be apparent to those of skill in the art. Accordingly, it should be understood that various applications, modifications, and substitutions may be made of equivalents without departing from the spirit of embodiments of the invention or the scope of the claims.
Various modifications and applications of the embodiments of the invention may occur to those who are skilled in the art, without departing from the true spirit or scope of the embodiments of the invention. It should be understood that the invention(s) is not limited to the embodiments set forth herein for purposes of exemplification, but is to be defined only by a fair reading of the appended claims, including the full range of equivalency to which each element thereof is entitled.
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| Number | Date | Country | |
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| 20190321220 A1 | Oct 2019 | US |
| Number | Date | Country | |
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| 61790759 | Mar 2013 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 14776563 | US | |
| Child | 16408283 | US |
