Patent Grant
11529258
The present technology generally relates to implantable medical devices and, in particular, to intraocular shunting systems and associated methods for selectively controlling fluid flow between different portions of a patient's eye.
Glaucoma is a degenerative ocular condition involving damage to the optic nerve that can cause progressive and irreversible vision loss. Glaucoma is frequently associated with ocular hypertension, an increase in pressure within the eye, and may result from an increase in production of aqueous humor (“aqueous”) within the eye and/or a decrease in the rate of outflow of aqueous from within the eye into the blood stream. Aqueous is produced in the ciliary body at the boundary of the posterior and anterior chambers of the eye. It flows into the anterior chamber and eventually into the venous vessels of the eye. Glaucoma is typically caused by a failure in mechanisms that transport aqueous out of the eye and into the blood stream.
Many aspects of the present technology can be better understood with reference to the following drawings. The components in the drawings are not necessarily drawn to scale. Instead, emphasis is placed on illustrating clearly the principles of the present technology. Furthermore, components can be shown as transparent in certain views for clarity of illustration only and not to indicate that the component is necessarily transparent. Components may also be shown schematically.
The present technology is directed to systems, devices, and methods for treating glaucoma. In particular, some embodiments provide shunts having a plurality of individually actuatable flow control elements that can control the flow of fluid through associated ports and/or channels in the shunt. For example, each individually actuatable flow control element can be actuated to substantially block and/or substantially unblock a corresponding port and/or channel, thereby inhibiting or permitting flow through the port and/or channel. Accordingly, the shunts described herein can be manipulated into a variety of configurations that provide different drainage rates based on whether the ports and/or channels are blocked or unblocked, therefore providing a titratable glaucoma therapy for draining aqueous from the anterior chamber of the eye. In embodiments, the flow control elements can be non-invasively adjusted after the shunt is implanted in the eye to allow for post-implant adjustments.
In many of the embodiments described herein, the shunting systems include ports and/or drainage channels that are configured to provide a different therapy level relative to other ports and/or drainage channels of the system. For example, a first port and/or channel may be associated with a first drainage rate and/or first fluid resistance, a second port and/or channel may be associated with a second drainage rate and/or second fluid resistance, and a third port and/or channel may be associated with a third drainage rate and/or third fluid resistance. As described below, this can be accomplished by having ports and/or drainage channels having different dimensions (e.g., diameters, cross-section areas, lengths, etc.). In some embodiments, the ports and channels are arranged as parallel fluid resistors relative to a primary drainage lumen. In other embodiments, the inflow ports and channels are arranged as serial fluid resistors relative to the primary drainage lumen.
In embodiments in which the inflow ports and channels are arranged as parallel fluid resistors relative to the primary drainage lumen, each individual port may be associated with a discrete and different relative resistance and/or flow. For example, a first port may enable a flow of 1X, a second port may enable a flow of 2X, and a third port may enable a flow of 3X. Moreover, because the ports are arranged as parallel fluid resistors, any combination of ports can be opened (e.g., unblocked) or closed (e.g., blocked, interfered with, etc.) to provide additional discrete relative resistances and/or drainage rates that differ from the discrete relative resistances and flows associated with each individual port. In the foregoing example, both the second and third ports can be opened to provide a flow of 5X. In some embodiments, the relative dimensions of the ports and/or channels can be selected to specifically provide the greatest number of discrete therapy levels. For example, in some embodiments, a ratio between the first drainage rate, second drainage rate, and third drainage rate can be about 1:2:4. Likewise a ratio between the first resistance, the second resistance, and the third resistance can be about 4:2:1. Without being bound theory, this is expected to increase the number of discrete therapy levels the systems can provide, which in turn is expected to enable a healthcare to specifically tailor the therapy level to a particular patient's needs.
In embodiments in which the inflow ports and channels are arranged as serial fluid resistors relative to a main drainage lumen, each individual inflow port may still be associated with a discrete resistance and/or drainage rate. However, unlike embodiments in which the ports are arranged as parallel fluid resistors, the systems cannot be manipulated to achieve a plurality of combined resistances and/or flow rates different than the discrete resistances and/or drainage rates provided by each individual port.
The terminology used in the description presented below is intended to be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific embodiments of the present technology. Certain terms may even be emphasized below; however, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section. Additionally, the present technology can include other embodiments that are within the scope of the examples but are not described in detail with respect to
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present technology. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features or characteristics may be combined in any suitable manner in one or more embodiments.
Reference throughout this specification to relative terms such as, for example, “generally,” “approximately,” and “about” are used herein to mean the stated value plus or minus 10%. Reference throughout this specification to the term “resistance” refers to fluid resistance unless the context clearly dictates otherwise. The terms “drainage rate” and “flow” are used interchangeably to describe the movement of fluid through a structure.
Although certain embodiments herein are described in terms of shunting fluid from an anterior chamber of an eye, one of skill in the art will appreciate that the present technology can be readily adapted to shunt fluid from and/or between other portions of the eye, or, more generally, from and/or between a first body region and a second body region. Moreover, while the certain embodiments herein are described in the context of glaucoma treatment, any of the embodiments herein, including those referred to as “glaucoma shunts” or “glaucoma devices” may nevertheless be used and/or modified to treat other diseases or conditions, including other diseases or conditions of the eye or other body regions. For example, the systems described herein can be used to treat diseases characterized by increased pressure and/or fluid build-up, including but not limited to heart failure (e.g., heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, etc.), pulmonary failure, renal failure, hydrocephalus, and the like. Moreover, while generally described in terms of shunting aqueous, the systems described herein may be applied equally to shunting other fluid, such as blood or cerebrospinal fluid, between the first body region and the second body region.
The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed present technology.
A. Intraocular Shunts for Glaucoma Treatment
Glaucoma refers to a group of eye diseases associated with damage to the optic nerve which eventually results in vision loss and blindness. As noted above, glaucoma is a degenerative ocular condition characterized by an increase in pressure within the eye resulting from an increase in production of aqueous within the eye and/or a decrease in the rate of outflow of aqueous from within the eye into the blood stream. The increased pressure leads to injury of the optic nerve over time. Unfortunately, patients often do not present with symptoms of increased intraocular pressure until the onset of glaucoma. As such, patients typically must be closely monitored once increased pressure is identified even if they are not symptomatic. The monitoring continues over the course of the disease so clinicians can intervene early to stem progression of the disease. Monitoring pressure requires patients to visit a clinic site on a regular basis which is expensive, time-consuming, and inconvenient. The early stages of glaucoma are typically treated with drugs (e.g., eye drops) and/or laser therapy. When drug/laser treatments no longer suffice, however, surgical approaches can be used. Surgical or minimally invasive approaches primarily attempt to increase the outflow of aqueous from the anterior chamber to the blood stream either by the creation of alternative fluid paths or the augmentation of the natural paths for aqueous outflow.
Referring to
Outflow resistance can change over time for a variety of reasons, e.g., as the outflow location goes through its healing process after surgical implantation of a shunt (e.g., shunt 100) or further blockage in the drainage network from the anterior chamber through the trabecular meshwork, Schlemm's canal, the collector channels, and eventually into the vein and the body's circulatory system. Accordingly, a clinician may desire to modify the shunt after implantation to either increase or decrease the outflow resistance in response to such changes or for other clinical reasons. For example, in many procedures the shunt is modified at implantation to temporarily increase its outflow resistance. After a period of time deemed sufficient to allow for healing of the tissues and stabilization of the outflow resistance, the modification to the shunt is reversed, thereby decreasing the outflow resistance. In another example, the clinician may implant the shunt and after subsequent monitoring of intraocular pressure determine a modification of the drainage rate through the shunt is desired. Such modifications can be invasive, time-consuming, and/or expensive for patients. If such a procedure is not followed, however, there is a high likelihood of creating hypotony (excessively low eye pressure), which can result in further complications, including damage to the optic nerve. In contrast, intraocular shunting systems configured in accordance with embodiments of the present technology allow the clinician to selectively adjust the flow of fluid through the shunt after implantation without additional invasive surgical procedures.
The shunts described herein can be implanted having a first drainage rate and subsequently remotely adjusted to achieve a second, different drainage rate. The adjustment can be based on the needs of the individual patient. For example, the shunt may be implanted at a first lower flow rate and subsequently adjusted to a second higher flow rate as clinically necessary. The shunts described herein can be delivered using either ab interno or ab externo implant techniques, and can be delivered via needles. The needles can have a variety of shapes and configurations to accommodate the various shapes of the shunts described herein. Details of the implant procedure, the implant devices, and bleb formation are described in greater detail in International Patent Application No. PCT/US20/41152, titled “MINIMALLY INVASIVE BLEB FORMATION DEVICES AND METHODS FOR USING SUCH DEVICES,” filed Jul. 8, 2020, the disclosure of which is incorporated by reference herein for all purposes.
In many of the embodiments described herein, the flow control assemblies are configured to introduce features that selectively impede or attenuate fluid flow through the shunt during operation. In this way, the flow control assemblies can incrementally or continuously change the flow resistance through the shunt to selectively regulate pressure and/or flow. The flow control assemblies configured in accordance with the present technology can accordingly adjust the level of interference or compression between a number of different positions, and accommodate a multitude of variables (e.g., TOP, aqueous production rate, native aqueous outflow resistance, and/or native aqueous outflow rate) to precisely regulate flow rate through the shunt.
The disclosed flow control assemblies can be operated using energy. This feature allows such devices to be implanted in the patient and then modified/adjusted over time without further invasive surgeries or procedures for the patient. Further, because the devices disclosed herein may be actuated via energy from an external energy source (e.g., a laser), such devices do not require any additional power to maintain a desired orientation or position. Rather, the actuators/fluid resistors disclosed herein can maintain a desired position/orientation without power. This can significantly increase the usable lifetime of such devices and enable such devices to be effective long after the initial implantation procedure.
B. Adjustable Glaucoma Shunts
In some embodiments, the drainage element 202 can be relatively flat such that its height is less than its width (e.g., the drainage element 202 has an oval, rectangular, or “D-shaped” cross sectional shape). In such embodiments, the drainage element 202 may have an outer diameter (e.g., height) of about 1000 microns (μm) or less, about 400 μm or less, or about 300 μm or less. The drainage element 202 can have an outer diameter value that is between any of the aforementioned values of outer diameter. In some embodiments, the drainage element may have an inner diameter of about 800 μm or less, about 300 μm or less, or about 200 μm or less. The drainage element 202 can have an inner diameter value that is between any of the aforementioned values of inner diameter. In some embodiments, the drainage element 202 can have a length that is about 2 mm, about 2.5 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 15 mm, or about 20 mm. The drainage element 202 can have a length that is between any of the aforementioned values of length. In other embodiments, the drainage element 202 can be substantially cylindrical. Without wishing to be bound by theory, having a relatively flat profile is expected to advantageously reduce interference with native tissue while providing increased stability of the shunt 200.
The shunt 200 can include a flow control mechanism 210 positioned at the first end portion 204 of the drainage element 202. When the shunt 200 is implanted in an eye, the first end portion 204 can reside within an anterior chamber and the second end portion 206 can reside in a desired outflow location (e.g., a bleb space, such as those described in International Patent Application No. PCT/US20/41152, previously incorporated by reference herein). In such embodiments, the flow control mechanism 210 is located within the anterior chamber. In other embodiments, the first end portion 204 can reside within the desired outflow location and the second end portion 206 can reside within the anterior chamber (e.g., fluid would flow from the outflow aperture 207 to the ports 208). In such embodiments, the flow control mechanism 210 is positioned outside of the anterior chamber (e.g., in the bleb space). Regardless of the orientation of the shunt 200, the shunt 200 is configured to drain aqueous from the anterior chamber when the shunt 200 is implanted in the eye. The shunt 200 may optionally have additional features that help secure the shunt 200 in place when implanted in the eye. For example, the shunt 200 can include arms, anchors, plates, or other suitable features (not shown) that can secure the shunt 200 to native tissue. The shunt 200 may also include an outer membrane or cover (e.g., a transparent and/or biocompatible membrane) that encases some or all of the shunt 200.
Referring now to
Each flow control element 211a-d includes a pair of anchors 212 (e.g., the first flow control element 211a includes a first anchor 212a and second anchor 212b) spaced apart along a length of the drainage element 202. In some embodiment, adjacent flow control elements 211a-d may share an anchor. For example, the second anchor 212b anchors both the first flow control element 211a and the second flow control element 211b. The anchors 212 are secured to the drainage element 202 such that at least one of the ports 208 is positioned generally between each pair of anchors. The anchors 212 can be secured to the drainage element 202 or other structure such that they do not move when the flow control elements 211a-d are actuated. For example, the anchors 212 may wrap around a circumference of the drainage element 202 and be secured thereto via a friction fit or other suitable attachment mechanism. In other embodiments, the anchors 212 do not wrap around the full circumference of the drainage element but nevertheless secure the flow control mechanism 210 to the drainage element 202 (e.g., via welding, gluing, or other suitable adhesion techniques).
Each individual flow control element 211a-d further includes a moveable gating element (e.g., flow control element 211a includes a gating element 216a, flow control element 211b includes a gating element 216b, etc., collectively referred to herein as gating element 216), a first actuation element (e.g., flow control element 211a includes a first actuation element 214a) extending between a first anchor (e.g., the first anchor 212a) and the corresponding gating element 216 (e.g., gating element 216a), and a second actuation element (e.g., flow control element 211b includes a second actuation element 214b) extending between a second anchor (e.g., the second anchor 212b) and the corresponding gating element 216. Each gating element 216a-d is configured to interface with (e.g., at least partially block or otherwise form a substantial or full fluid seal with) a corresponding port 208. The actuation elements can be selectively activated to selectively move the corresponding gating element 216 between one or more positions blocking (or partially blocking) the corresponding port 208 and one or more positions unblocking (or at partially unblocking) the corresponding port 208. For example, (a) the gating element 216a of the first flow control element 211a can be moved between a first open position permitting fluid to flow into the drainage element 202 via the corresponding port 208 and a first closed position substantially preventing fluid from flowing into the drainage element 202 via the corresponding port 208, (b) the gating element 216b of the second flow control element 211b can be moved between a second open position permitting fluid to flow into the drainage element 202 via the corresponding port 208, and a second closed position substantially preventing fluid from flowing into the drainage element 202 via the corresponding port 208, (c) the gating element 216c of the third flow control element 211c can be moved between a third open position permitting fluid to flow into the drainage element 202 via the corresponding port 208, and a third closed position substantially preventing fluid from flowing into the drainage element 202 via the corresponding port 208, and (d) the gating element 216d of the fourth flow control element 211d can be moved between a fourth open position permitting fluid to flow into the drainage element 202 via the corresponding port 208, and a fourth closed position substantially preventing fluid from flowing into the drainage element 202 via the corresponding port 208. Although described as “blocking” and “unblocking” the inflow ports when in the closed and open positions, the gating element can also be described as not interfering with and/or imparting a first fluid resistance through the outlet when in the open position and interfering with and/or imparting a second fluid resistance greater than the first fluid resistance when in the closed position.
The gating elements 216 can be moved by actuating the actuation elements 214. For example, actuating the second actuation element 214a can move the gating element 216a in a first direction, and actuating the first actuation element 114b can move the gating element 216a in a second direction generally opposite the first direction. To facilitate the foregoing movement of the gating elements 216, the actuation elements can be composed at least partially of a shape memory material (e.g., a shape memory alloy) or other suitable material that is configured to change shape upon application of energy. For example, in some embodiments the actuation elements are composed of nitinol. In such embodiments, the actuation elements (and/or regions thereof) can be transitionable at least between a first material phase or state (e.g., a martensitic state, a R-phase, a composite state between martensitic and R-phase, etc.) and a second material phase or state (e.g., an austenitic state, an R-phase state, a composite state between austenitic and R-phase, etc.). In the first material state, the actuation element or select region thereof may be deformable (e.g., plastic, malleable, compressible, expandable, etc.). In the second material state, the actuation element or select region thereof may have a preference toward a specific preferred geometry (e.g., original geometry, manufactured or fabricated geometry, heat set geometry, etc.). As described below, the actuation elements can be individually and/or selectively transitioned between the first material state and the second material state by applying energy (e.g., heat, light, etc.) to the actuation element to heat the actuation element above a transition temperature (e.g., a phase transition temperature). If the actuation element is deformed relative to its preferred geometry, the transition from the first material state to the second material state can induce a dimensional change in the actuation element. In some embodiments, the dimensional change is an expansion. In some embodiments, the dimensional change is a contraction (e.g., compression). In some embodiments, the energy is applied from an energy source positioned external to the eye (e.g., a laser), which can enable a user to non-invasively adjust the shunt.
The flow control element 211a (e.g., the first actuation element 214a or the second actuation element 214b) can be actuated to move (e.g., translate) the gating element 216a along the axial length of the drainage element 202 between the first anchor 212a and the second anchor 212b. This movement of the gating element 216a can cause it to block (e.g., partially or fully block) and/or unblock (e.g., partially or fully unblock) the associated port 208. For example, in embodiments in which the first actuation element 214a is compressed relative to its preferred geometry, heating the first actuation element 214a above its transition temperature can cause the first actuation element 214a to expand and/or stiffen (thereby expanding in length). Because the first anchor 212a and the second anchor 212b are secured in place (e.g., they do not move relative to the drainage element 202), the first actuation element 214a pushes the gating element 216a away from the first anchor 212a as it expands (and toward the second anchor 212b). As illustrated in
In some embodiments, the actuation elements are configured to retain or substantially retain their shape following application of energy. For example, if energy is applied to the first actuation element 214a to transition the first flow control element 211a from the configuration shown in
Although the foregoing description is directed to the first flow control element 211a, the components associated with the flow control elements 211b-d can be actuated in a similar manner. Moreover, additional details regarding the operation of shape memory actuators for glaucoma shunts are described in U.S. Patent App. Publication No. 2020/0229982 and International Patent Application Nos. PCT/US20/55144 and PCT/US20/55141, the disclosures of which are incorporated by reference herein in their entireties and for all purposes.
The shunt 200 can be set such that, at body temperature, all, some, or none of the ports 208 are blocked by the corresponding gating elements 216. Accordingly, in some embodiments the shunt 200 can have a base configuration in which all, some, or none of the ports 208 are blocked by the corresponding gating elements 216.
The drainage of aqueous through the shunt 200 can be selectively controlled by selectively blocking and/or unblocking the ports 208 using the flow control elements 211a-d. For example, to provide a first level of therapy having a first drainage rate and a first flow resistance, one of the ports 208 can be accessible/unblocked, while the remaining ports 208 can be inaccessible/blocked. To provide a second level of therapy having a second drainage rate that is greater than the first drainage rate (e.g., a second flow resistance less than the first flow resistance), two of the ports 208 can be accessible/unblocked, while the remaining ports 208 are inaccessible/blocked. As one skilled in the art will appreciate, the flow control elements 211a-d can be actuated such that any combination of ports 208 are blocked or unblocked to provide multiple different therapy levels.
To increase the discrete levels of therapy that can be provided by the shunt 200, each port 208 may be configured to provide a different level of therapy (e.g., resistance) relative to each other when the shunt 200 is exposed to a given pressure.
Each of the ports 208a-d can correspond to an individual flow control element 211a-d (omitted in
Each of the ports 208a-d can be associated with a desired fluid flow and/or drainage rate relative to other ports 208a-c (e.g., when operating under a given pressure). In some embodiments, the relative drainage rates provided through each individual port 208a-d increases by a common value from the port 208a to the port 208d under a given pressure. For example, the port 208a may be associated with a relative drainage rate of about X, the port 208b may be associated with a relative drainage rate of about 2X, the port 208c may be associated with a relative drainage rate of about 3X, and the port 208d may be associated with a relative drainage rate of about 4X. In such embodiments, the ratio of relative flow rates for the ports 208a-d is 1:2:3:4. In such embodiments, the flow control elements 211a-d can be manipulated to achieve any drainage rate between about X (only the port 208a is unblocked) and about 10X (all of the ports 208a-d are unblocked). In embodiments with only three ports 208a-c, the corresponding flow control elements can be manipulated to achieve any drainage rate between about X (only the port 208a is unblocked) and about 6X (all of the ports 208a-c are unblocked). Table 1 below reflects the relative drainage rate (flow) and associated resistance values for embodiments in which a ratio of the relative flow rates for the ports 208a-d is 1:2:3:4.
As reflected in Table 1 above, the same relative flow value (Q) can be attained via different combinations of open and closed ports 208a-d (e.g., flow values of 3, 4, 5, 6, and 7). Therefore, despite having 15 potential combinations of open and closed ports in the illustrated embodiment (16 if all the ports 208a-d are closed), only 10 discrete therapy levels are provided.
In other embodiments, the relative drainage rates through the respective ports 208a-d do not increase by a common value from the port 208a to the port 208d, but rather are selectively sized to achieve a greater number of discrete possible drainage rates (e.g., to avoid overlapping values). For example, in an embodiment having just three ports 208a-c, the port 208a may be associated with a relative drainage rate of about X, the port 208b may be associated with a relative drainage rate of about 2X, and the port 208c may be associated with a relative drainage rate of about 4X. In such embodiments, the ratios of relative flow rates for the ports 208a-c is 1:2:4. The ports 208a-c can be selectively blocked and unblocked by the corresponding flow control elements 311a-c to achieve a variety of desired drainage rates. For example, if only the port 208a is unblocked, the drainage rate is about X, if only the port 208b is unblocked, the drainage rate is about 2X, if both the port 208a and 208b are unblocked, the drainage rate is about 3X, if only the port 208c is unblocked, the drainage rate is about 4X, if the port 208a and 208c are unblocked, the drainage rate is about 5X, if the port 208b and 208c are unblocked, the drainage rate is about 6X, and if ports 208a, 208b, and 208c are all unblocked, the drainage rate is about 7X. Unlike the example provided above, in which a shunt with three ports having a relative drainage ratio of 1:2:3 can provide six discrete potential drainage rates, a shunt with three ports with a relative drainage ratio of 1:2:4 can provide at least seven different potential drainage rates. Accordingly, by varying the dimensions of the ports 208 as described above, a greater number of relative drainage rates can be accomplished with fewer number of ports 208. In embodiments having four ports 208, the port 208d can have a relative drainage rate of about 8X to further increase the number of unique drainage rates possible (e.g., the ratio of relative flow rates for the ports 208a-d is 1:2:4:8). A user can therefore select which ports 208 are blocked and which ports 208 are unblocked to achieve any of the desired drainage rates. Table 2 below reflects the relative drainage rate (flow) and associated resistance values for embodiments in which a ratio of the relative flow rates for the ports 208a-d is 1:2:4:8.
Of course, the ratios of relative flow rates for the ports 208a-c can be values other than 1:2:4:8 or 1:2:3:4. In some embodiments, for example, the ratio can be 1:1:1:1, 1:1:2:2, 1:1:1:2, etc. In other embodiments, the ratio may be random (e.g., 1:6:2:3, 4:2:5:1, etc.).
The foregoing flow characteristics can also be described in terms of the resistances provided by each individual port 208a-d. For example, when unblocked or otherwise accessible, the port 208a can have a first resistance, the port 208b can have a second resistance less than the first resistance, the port 208c can have a third resistance less than the second resistance, and the port 208d can have a fourth resistance less than the third resistance. The resistances can have a predetermined ratio. In some embodiments, for example, the ratio of the resistance provided port 208a to the port 208b to the port 208c to the port 208d can be 4:3:2:1, 8:4:2:1, 1:1:1:1, or other ratios. Table 3 below reflects the relative resistance and associated flow for embodiments in which a ratio of the relative resistances for the ports 208a-d is 4:3:2:1. Table 4 below reflects the relative resistance and associated flow for embodiments in which a ratio of the relative resistances for the ports 208a-d is 1:2:4:8.
As one skilled in the art will appreciate from the disclosure herein, the shunt 200 and other shunts described herein can have two, three, four, five, six, seven, eight, or more ports 208, each with a corresponding flow control element 211. Increasing the number of ports 208 generally increases the number of different drainage rates that can be implemented because as the number of ports 208 increases, the number of unique combinations of blocked and/unblocked ports increases as well. As described above, the ports 208 can also be selectively sized to provide the greatest number of potential therapy levels. For example, in embodiments with two ports, the ratio of the relative flow rates for the ports can be about 1:2 and/or the ratio of the relative resistances for the ports can be about 2:1 (e.g., producing a total of four discrete therapy levels). In other embodiments with two ports, the ratio of the relative flow rates is about 1:1 and/or the ratio of the relative resistances is about 1:1. In embodiments with three ports, the ratio of the relative flow rates for the ports can be about 1:2:4 and/or the ratio of the relative resistances for the ports can be about 4:2:1 (e.g., producing a total of eight discrete therapy levels). In other embodiments with three ports, the ratio of the relative flow rates is about 1:1:1 or about 1:2:3, and/or the ratio of the relative resistances is about 1:1:1 or about 3:2:1. In embodiments with four ports, the ratio of the relative flow rates for the ports can be about 1:2:4:8 and/or the ratio of the relative resistances for the ports can be about 8:4:2:1 (producing a total of sixteen discrete therapy levels). In other embodiments with four ports, the ratio of the relative flow rates is about 1:1:1:1 or about 1:2:3:4, and/or the ratio of the relative resistances is about 1:1:1:1 or about 4:3:2:1. In embodiments with five ports, the ratio of the relative flow rates for the ports can be about 1:2:4:8:16 and/or the ratio of the relative resistances for the ports can be about 16:8:4:2:1 (producing a total of thirty-two discrete therapy levels). In other embodiments with five ports, the ratio of the relative flow rates is about 1:1:1:1:1 or about 1:2:3:4:5, and/or the ratio of the relative resistances is about 1:1:1:1:1 or about 5:4:3:2:1.
In some embodiments, the shunt 200 may include a plurality of discrete and fluidly isolated lumens or channels associated with individual ports 208. In such embodiments, the therapy level (e.g., drainage rate, resistance, etc.) may be determined by the relative dimensions of the lumens, not the number or size of the ports 208. For example, each lumen may have a different dimension to impart a different flow resistance. In such embodiments, the shunt 200 can still include different size ports 208 (
The above description primarily describes potential flow rates and resistances under a binary setting in which the ports 208a-d are either open or closed. However, in some embodiments, the gating elements 216 can be manipulated such that the ports 208a-d occupy one or more positions between fully open or fully closed. This can further increase the number of discrete therapy levels that the shunt 200 can provide. In yet other embodiments, the gating elements 216 may permit some fluid to leak through the ports 208a-d even in the closed positions (e.g., the gating elements 216 do not form a perfect fluid seal with the ports 208a-d when in the closed position).
The techniques and actuation assemblies described above can also be used with other types of shunts and drainage elements. For example,
The shunt 400 can include a flow control mechanism (not shown) operably coupled to the drainage plate 440 to control the flow of fluid through the channels 422. In some embodiments, the flow control mechanism includes a plurality of individually actuatable flow control elements associated with individual inflow ports 408 and channels 422. For example, in some embodiments, a flow control mechanism generally similar to the flow control mechanism 210 described with respect to
In some embodiments, the channels 422 may each have the same or about the same flow resistance. In embodiments in which the channels 422 have the same or about the same flow resistance, opening additional channels 422 is expected to result in a stepwise increase in the drainage rate, and blocking additional channels 422 is expected to result in a stepwise decrease in the drainage rate. For example, moving from a single open channel 422 to two open channels 422 is expected to generally double the drainage rate, while moving from two open channels 422 to three open channels 422 is expected to generally increase the drainage rate by 50 percent. However, the total number of unique resistances and thus flow rates that can be achieved is not maximized, since the resistance and flow when only a first lumen is unblocked is the same as the resistance and flow when only a second lumen in unblocked.
In other embodiments, the channels 422 may have different resistances and thus different relative drainage rates. For example, in some embodiments, each individual channel 422 may be associated with a desired drainage rate and/or resistance relative to one another. For example, a first channel may be associated with a drainage rate of about X, a second channel may be associated with a drainage rate of about 2X, a third channel may be associated with a drainage rate of about 4X, and so on. As described above with reference to the ports 208, a greater number of drainage rates can be accomplished with fewer channels 422 when each channel 422 is associated with a different drainage rate. Flow resistance through the channels 422, and thus drainage rates through the channels 422, can be varied based on, for example, a length of the channel and/or a diameter of the channel. The length of the channel is generally proportional to the resistance of the channel, whereas the diameter of the channel is generally inversely proportional to the resistance of the channel. Accordingly, each individual channel 422 may have a unique length, diameter, or length and diameter combination that gives it a certain resistance. Individual channels 422 can then be selectively opened (or closed) to achieve a desired flow rate.
The flow characteristics through parallel fluid resistors such as the shunt 400 (and the shunt 200) can be similar to current flowing through an electrical circuit having a plurality of resistors arranged in parallel.
The present technology also provides shunting systems having a plurality of inflow ports operating as serial fluid resistors. For example,
The shunt 500 can include a flow control mechanism (not shown) operably coupled to the drainage plate 540 to control the flow of fluid out of the outflow ports 509 and into the lumen. The flow control mechanism can include a plurality of individually actuatable flow control elements associated with individual outflow ports 509. For example, in some embodiments, a flow control mechanism generally similar to the flow control mechanism 210 (
The plate 540 is configured to act as a serial resister. For example, the resistance is provided by the channel 522 (rather than the inflow port 508 and/or the outflow ports 509) and is based on the distance between the inflow port 508 and the closest open outflow port 509. For example, if the outflow port 509 spaced furthest apart from the inflow port 508 is the only outflow port 509 open, then the resistance to flow is the greatest (e.g., by virtue of the fluid having to travel the greatest distance through the channel 522). If the outflow port 509 closest to the inflow port 508 is open, then the resistance is the least (e.g., by virtue of the fluid having to travel the shortest distance through the channel 522). In such embodiments, the channels/apertures behave as if they are in series, and thus the number of discrete resistances and drainage rates is generally equal to the number of outflow apertures 509.
The flow characteristics through serial fluid resistors such as the shunt 500 can be similar to current flowing through an electrical circuit having a plurality of resistors arranged in series.
The present technology further includes methods of shunting fluids through the shunting systems and shunts described herein (e.g., to drain aqueous from the anterior chamber for treating glaucoma). The methods can incorporate any of the techniques described above, including, for example, selectively actuating one or more flow control elements to open and/or close one or more ports (e.g. inflow ports) on a shunt to achieve a target resistance and/or flow. The methods may also include selectively actuating one or more flow control elements to open and/or close one or more ports until a target intraocular pressure is attained.
In some embodiments, the ports can all be simultaneously unblocked to provide the lowest resistance and highest flow for a given pressure. This may be done in a healthcare provider's office to quickly reduce intraocular pressure. Once a target intraocular pressure is achieved, some or all of the ports can be closed to provide a flow and resistance more suitable for chronic therapy. Without intending to be bound by theory, use of adjustable shunts such as those provided herein may be able to safely provide higher flow and lower resistance than conventional static (e.g., non-adjustable) shunts. For example, conventional static shunts generally do not provide high flow or low resistance in order to avoid inducing hypotony. In contrast, the shunts of the present technology can provide high flow and low resistance (e.g., by opening all the ports) that, if left unchanged for a prolonged period, could lead to hypotony. However, before hypotony occurs, a healthcare provider can adjust the shunt to lower flow and increase resistance. One expected advantage of this is that a healthcare provider can more quickly reduce intraocular pressure in the patient.
Several aspects of the present technology are set forth in the following examples:
1. A system for draining fluid, the system comprising:
2. The system of example 1 wherein:
3. The system of example 2 wherein the second relative resistance is less than the first relative resistance, and wherein the third relative resistance is less than the first relative resistance
4. The system of example 3 wherein a ratio between the first relative resistance, the second relative resistance, and the third relative resistance is about 4:2:1.
5. The system of example 3 wherein a ratio between the first relative resistance, the second relative resistance, and the third relative resistance is about 3:2:1.
6. The system of example 2 wherein a ratio between the first relative resistance, the second relative resistance, and the third relative resistance is about 1:1:1.
7. The system of example 1 wherein:
8. The system of example 7 wherein the second relative drainage rate is greater than the first relative drainage rate, and wherein the third relative drainage rate is greater than the second relative drainage rate.
9. The system of example 8 wherein a ratio between the first relative drainage rate, the second relative drainage rate, and the third relative drainage rate is about 1:2:4.
10. The system of example 8 wherein a ratio between the first relative drainage rate, the second relative drainage rate, and the third relative drainage rate is about 1:2:3.
11. The system of example 7 wherein a ratio between the first relative drainage rate, the second relative drainage rate, and the third relative drainage rate is about 1:1:1.
12. The system of any of examples 1-11 wherein the drainage element has a first channel fluidly coupled to the first port, a second channel fluidly coupled to the second port, and a third channel fluidly coupled to the third port.
13. The system of example 12 wherein the first channel is configured to provide a greater relative resistance than the second channel, and wherein the second channel is configured to provide a greater relative resistance than the third channel.
14. The system of example 13 wherein the first channel has a first cross sectional area, the second channel has a second cross sectional area greater than the first cross sectional area, and the third channel has a third cross sectional area greater than the second cross sectional area.
15. The system of any of examples 1-14 wherein the first port has a first area, the second port has a second area greater than the first area, and the third port has a third area greater than the second area.
16. The system of any of examples 1-15 wherein the first port includes a single aperture, the second port includes two apertures, and the third port includes three or more apertures.
17. The system of any of examples 1-16 wherein the first port is a first inflow port, the second port is a second inflow port, and the third port is a third inflow port.
18. The system of any of examples 1-17 wherein the first body region is an anterior chamber, and wherein the fluid is aqueous.
19. A system for draining fluid, the system comprising:
20. The system of example 19 wherein the ratio between the first relative drainage rate and the second relative drainage rate is 1:2.
21. The system of example 20 wherein when both the first inflow port and the second inflow port are unblocked, the system is configured to provide a third relative drainage rate through the drainage element that is greater than the first relative drainage rate and the second relative drainage rate.
22. The system of example 21 wherein a ratio between the first, second, and third relative drainage rates is 1:2:3.
23. The system of any of examples 19-22 wherein the first inflow port includes a single aperture and the second inflow port includes a plurality of apertures.
24. The system of any of examples 19-23 wherein the first inflow port has a first area and the second inflow port has a second area greater than the first area.
25. The system of any of examples 19-24 wherein the drainage element includes (i) a first lumen extending between the first inflow port and the second end region, and (ii) a second lumen extending between the second inflow port and the second end region, and wherein the first lumen is configured to provide a different resistance to fluid flow than the second lumen.
26. The system of any of examples 19-25 wherein the drainage element further comprises a third inflow port, and wherein when the third inflow port is unblocked and the first and second inflow ports are blocked, the system is configured to provide a third relative drainage rate through the drainage element.
27. The system of example 26 wherein a ratio between the first relative drainage rate, the second relative drainage rate, and the third relative drainage rate is about 1:2:3.
28. The system of example 26 wherein a ratio between the first relative drainage rate, the second relative drainage rate, and the third relative drainage rate is about 1:2:4.
29. The system of example 25 wherein the drainage element further comprises a fourth inflow port, and wherein when the fourth inflow port is unblocked and the first, second, and third inflow ports are blocked, the system is configured to provide a fourth relative drainage rate through the drainage rate, and wherein a ratio between the first, second, third, and fourth relative drainage rates is about 1:2:4:8.
30. The system of any of examples 19-29 wherein the first body region is an anterior chamber of an eye, and wherein the fluid is aqueous.
31. The system of any of examples 19-30 wherein the drainage element includes a plate extending from the first end portion, and wherein the plate includes the first and second inflow ports.
32. An adjustable shunt, comprising:
33. The adjustable shunt of example 32 wherein the first drainage rate, the second drainage rate, and the third drainage rate are predetermined relative drainage rates, and wherein the first drainage rate is about X, the second drainage rate is about 2X, and the third drainage rate is about 3X.
34. The adjustable shunt of example 32 wherein the first drainage rate, the second drainage rate, and the third drainage rate are predetermined relative drainage rates, and wherein the first drainage rate is about X, the second drainage rate is about 2X, and the third drainage rate is about 4X.
35. The adjustable shunt of example 34 wherein, when more than one inflow port is open, the shunt is configured to provide a fourth relative drainage rate that is different than the first drainage rate, the second drainage rate, and the third drainage rate.
36. The adjustable shunt of example 34 wherein the shunt is configured to provide additional predetermined relative drainage rates including—
37. The adjustable shunt of example 36 wherein the flow control elements are selectively actuatable to achieve any of the predetermined relative drainage rates.
38. A method of treating glaucoma, the method comprising:
39. The method of example 38 wherein the first inflow port provides a first drainage rate when only the first inflow port is unblocked, and wherein the second inflow port provides a second drainage rate greater than the first drainage rate when only the second inflow port is unblocked.
40. The method of example 38 or 39 wherein actuating at least one of the individually actuatable flow control elements comprises applying energy to at least one of the individually actuatable flow control elements.
41. The method of example 40 wherein the energy is non-invasive energy.
42. An adjustable shunt, comprising:
43. The adjustable shunt of example 42 wherein the first inflow port and the second inflow port have different diameters.
44. The adjustable shunt of example 42 wherein the first inflow port comprises a single inflow aperture and the second inflow port comprises at least two inflow apertures.
45. The adjustable shunt of any of examples 42-44 wherein the first inflow port is configured to provide a first drainage rate through the shunt when only the first inflow port is unblocked, and wherein the second inflow port is configured to provide a second drainage rate through the shunt that is greater than the first drainage rate when only the second inflow port is unblocked.
46. The adjustable shunt of any of examples 42-45 wherein the drainage element includes a plate extending from the first end portion, and wherein the plate includes the plurality of inflow ports.
47. The adjustable shunt of example 46 wherein the plate includes—
48. The adjustable shunt of example 47 wherein the first flow control element is positioned between the first channel and the lumen, and wherein the second flow control element is positioned between the second channel and the lumen.
49. The adjustable shunt of example 47 wherein the first channel extends between the first flow control element and the lumen, and wherein the second channel extends between the second flow control element and the lumen.
The above detailed description of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology as those skilled in the relevant art will recognize. For example, any of the features of the intraocular shunts described herein may be combined with any of the features of the other intraocular shunts described herein and vice versa. Moreover, although steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.
From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but well-known structures and functions associated with intraocular shunts have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the technology. Where the context permits, singular or plural terms may also include the plural or singular term, respectively.
Unless the context clearly requires otherwise, throughout the description and the examples, the words “comprise,” “comprising,” and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to.” As used herein, the terms “connected,” “coupled,” or any variant thereof, means any connection or coupling, either direct or indirect, between two or more elements; the coupling of connection between the elements can be physical, logical, or a combination thereof. Additionally, the words “herein,” “above,” “below,” and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of this application. Where the context permits, words in the above Detailed Description using the singular or plural number may also include the plural or singular number respectively. As used herein, the phrase “and/or” as in “A and/or B” refers to A alone, B alone, and A and B. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with some embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.
This application is a 35 U.S.C. § 371 U.S. National Phase application of International Patent Application No. PCT/US2021/014774, filed Jan. 22, 2021, which claims priority to U.S. Provisional Patent Application No. 62/965,117, filed Jan. 23, 2020, the disclosures of which are incorporated herein by reference in their entireties.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/014774 | 1/22/2021 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2021/151007 | 7/29/2021 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 4401107 | Harber et al. | Aug 1983 | A |
| 4595390 | Hakim et al. | Jun 1986 | A |
| 5070697 | Van Zeggeren | Dec 1991 | A |
| 5123906 | Kelman | Jun 1992 | A |
| 5300020 | L'Esperance, Jr. | Apr 1994 | A |
| 6077299 | Adelberg et al. | Jun 2000 | A |
| 6203513 | Yaron et al. | Mar 2001 | B1 |
| 6261256 | Ahmed | Jul 2001 | B1 |
| 6450984 | Lynch et al. | Sep 2002 | B1 |
| 6508779 | Suson | Jan 2003 | B1 |
| 6626858 | Lynch et al. | Sep 2003 | B2 |
| 6638239 | Bergheim et al. | Oct 2003 | B1 |
| 6666841 | Gharib et al. | Dec 2003 | B2 |
| 6736791 | Tu et al. | May 2004 | B1 |
| 6789447 | Zinck | Sep 2004 | B1 |
| 7025740 | Ahmed | Apr 2006 | B2 |
| 7207965 | Simon | Apr 2007 | B2 |
| 7354416 | Quiroz-Mereado et al. | Apr 2008 | B2 |
| 7364564 | Sniegowski et al. | Apr 2008 | B2 |
| 7458953 | Peyman | Dec 2008 | B2 |
| 7699882 | Stamper et al. | Apr 2010 | B2 |
| 7717872 | Shetty | May 2010 | B2 |
| 7947008 | Grahn et al. | May 2011 | B2 |
| 8012134 | Claude et al. | Sep 2011 | B2 |
| 8206440 | Guarnieri | Jun 2012 | B2 |
| 8298240 | Giger et al. | Oct 2012 | B2 |
| 8308701 | Horvath et al. | Nov 2012 | B2 |
| 8506515 | Burns et al. | Aug 2013 | B2 |
| 8540659 | Berlin | Sep 2013 | B2 |
| 8579848 | Field et al. | Nov 2013 | B2 |
| 8585629 | Grabner et al. | Nov 2013 | B2 |
| 8663303 | Horvath et al. | Mar 2014 | B2 |
| 8721702 | Romoda et al. | May 2014 | B2 |
| 8753305 | Field et al. | Jun 2014 | B2 |
| 8758290 | Horvath et al. | Jun 2014 | B2 |
| 8765210 | Romoda et al. | Jul 2014 | B2 |
| 8771220 | Nissan et al. | Jul 2014 | B2 |
| 8801766 | Reitsamer et al. | Aug 2014 | B2 |
| 8828070 | Romoda et al. | Sep 2014 | B2 |
| 8852136 | Horvath et al. | Oct 2014 | B2 |
| 8852137 | Horvath et al. | Oct 2014 | B2 |
| 8852256 | Horvath et al. | Oct 2014 | B2 |
| 8882781 | Smedley et al. | Nov 2014 | B2 |
| 8915877 | Cunningham et al. | Dec 2014 | B2 |
| 8974511 | Horvath et al. | Mar 2015 | B2 |
| 9017276 | Horvath et al. | Apr 2015 | B2 |
| 9095411 | Horvath et al. | Aug 2015 | B2 |
| 9095413 | Romoda et al. | Aug 2015 | B2 |
| 9113994 | Horvath et al. | Aug 2015 | B2 |
| 9125723 | Horvath et al. | Sep 2015 | B2 |
| 9192516 | Horvath et al. | Nov 2015 | B2 |
| 9226851 | Gunn | Jan 2016 | B2 |
| 9271869 | Horvath et al. | Mar 2016 | B2 |
| 9283116 | Romoda et al. | Mar 2016 | B2 |
| 9326891 | Horvath et al. | May 2016 | B2 |
| 9375347 | Stergiopulos | Jun 2016 | B2 |
| 9393153 | Horvath et al. | Jul 2016 | B2 |
| 9555410 | Brammer et al. | Jan 2017 | B2 |
| 9585789 | Silvestrini et al. | Mar 2017 | B2 |
| 9585790 | Horvath et al. | Mar 2017 | B2 |
| 9592154 | Romoda et al. | Mar 2017 | B2 |
| 9610195 | Horvath | Apr 2017 | B2 |
| 9636254 | Yu et al. | May 2017 | B2 |
| 9655778 | Tyler | May 2017 | B2 |
| 9655779 | Bigler et al. | May 2017 | B2 |
| 9693900 | Gallardo Inzunza | Jul 2017 | B2 |
| 9693901 | Horvath et al. | Jul 2017 | B2 |
| 9757276 | Penhasi | Sep 2017 | B2 |
| 9808373 | Horvath et al. | Nov 2017 | B2 |
| 9877866 | Horvath et al. | Jan 2018 | B2 |
| 9883969 | Horvath et al. | Feb 2018 | B2 |
| 9980854 | Horvath et al. | May 2018 | B2 |
| 10004638 | Romoda et al. | Jun 2018 | B2 |
| 10080682 | Horvath et al. | Sep 2018 | B2 |
| 10085884 | Reitsamer et al. | Oct 2018 | B2 |
| 10154924 | Clauson et al. | Dec 2018 | B2 |
| 10159600 | Horvath et al. | Dec 2018 | B2 |
| 10195078 | Horvath et al. | Feb 2019 | B2 |
| 10195079 | Horvath et al. | Feb 2019 | B2 |
| 10231871 | Hill | Mar 2019 | B2 |
| 10238536 | Olson et al. | Mar 2019 | B2 |
| 10285853 | Rangel-Friedman et al. | May 2019 | B2 |
| 10307293 | Horvath et al. | Jun 2019 | B2 |
| 10314743 | Romoda et al. | Jun 2019 | B2 |
| 10322267 | Hakim | Jun 2019 | B2 |
| 10335030 | Alhourani | Jul 2019 | B2 |
| 10369048 | Horvath et al. | Aug 2019 | B2 |
| 10405903 | Biesinger et al. | Sep 2019 | B1 |
| 10342703 | Siewert et al. | Nov 2019 | B2 |
| 10463537 | Horvath et al. | Nov 2019 | B2 |
| 10470927 | Horvath et al. | Nov 2019 | B2 |
| 10363168 | Schieber et al. | Dec 2019 | B2 |
| 10492948 | Baerveldt | Dec 2019 | B2 |
| 10524959 | Horvath | Jan 2020 | B2 |
| 10524958 | Camras et al. | Mar 2020 | B2 |
| 10596035 | Stergiopulos et al. | Apr 2020 | B2 |
| 10758412 | Velasquez | Apr 2020 | B2 |
| 11122975 | Rodger et al. | Jan 2021 | B2 |
| 10912675 | Lubatschowski | Feb 2021 | B2 |
| 11166847 | Badawi et al. | Feb 2021 | B2 |
| 10952897 | Smith | Mar 2021 | B1 |
| 10960074 | Berdahl | Mar 2021 | B2 |
| 11039954 | Cohen et al. | Jun 2021 | B2 |
| 11058581 | Mixter et al. | Jul 2021 | B2 |
| 11065154 | Sponsel et al. | Jul 2021 | B1 |
| 11083624 | Stein et al. | Aug 2021 | B2 |
| 11166848 | Mixter et al. | Nov 2021 | B2 |
| 11166849 | Mixter et al. | Nov 2021 | B2 |
| 11291585 | Schultz et al. | Apr 2022 | B2 |
| 20010011585 | Cassidy et al. | Aug 2001 | A1 |
| 20020177891 | Miles et al. | Nov 2002 | A1 |
| 20020193725 | Odrich | Dec 2002 | A1 |
| 20030127090 | Gifford et al. | Jul 2003 | A1 |
| 20030163079 | Burnett | Aug 2003 | A1 |
| 20040010219 | McCusker et al. | Jan 2004 | A1 |
| 20040254520 | Porteous et al. | Dec 2004 | A1 |
| 20050049578 | Tu et al. | Mar 2005 | A1 |
| 20060155300 | Stamper et al. | Jul 2006 | A1 |
| 20070010837 | Tanaka | Jan 2007 | A1 |
| 20070078371 | Brown et al. | Apr 2007 | A1 |
| 20070088432 | Solovay et al. | Apr 2007 | A1 |
| 20080077071 | Yaron et al. | Mar 2008 | A1 |
| 20080119891 | Miles et al. | May 2008 | A1 |
| 20080125691 | Yaron | May 2008 | A1 |
| 20080228127 | Burns et al. | Sep 2008 | A1 |
| 20090036818 | Grahn et al. | Feb 2009 | A1 |
| 20090243956 | Keilman et al. | Oct 2009 | A1 |
| 20090326517 | Bork et al. | Dec 2009 | A1 |
| 20100234791 | Lynch et al. | Sep 2010 | A1 |
| 20100241077 | Geipel et al. | Sep 2010 | A1 |
| 20110105986 | Bronstein et al. | May 2011 | A1 |
| 20120065570 | Yeung et al. | Mar 2012 | A1 |
| 20120089073 | Cunningham, Jr. | Apr 2012 | A1 |
| 20130131577 | Bronstein et al. | May 2013 | A1 |
| 20130150773 | Nissan et al. | Jun 2013 | A1 |
| 20130150776 | Bohm et al. | Jun 2013 | A1 |
| 20130158381 | Rickard | Jun 2013 | A1 |
| 20130197621 | Ryan et al. | Aug 2013 | A1 |
| 20130199646 | Brammer et al. | Aug 2013 | A1 |
| 20130205923 | Brammer et al. | Aug 2013 | A1 |
| 20130211312 | Gelvin | Aug 2013 | A1 |
| 20130267887 | Kahook et al. | Oct 2013 | A1 |
| 20130317412 | Dacquay et al. | Nov 2013 | A1 |
| 20130338564 | Rickard et al. | Dec 2013 | A1 |
| 20140046439 | Dos Santos et al. | Feb 2014 | A1 |
| 20140081195 | Clauson | Mar 2014 | A1 |
| 20140309611 | Wilt et al. | Oct 2014 | A1 |
| 20150011926 | Reitsamer et al. | Jan 2015 | A1 |
| 20150034217 | Vad | Feb 2015 | A1 |
| 20150045716 | Gallardo Inzunza | Feb 2015 | A1 |
| 20150142049 | Delgado et al. | May 2015 | A1 |
| 20150230843 | Palmer et al. | Aug 2015 | A1 |
| 20150313603 | Bodewadt et al. | Nov 2015 | A1 |
| 20160151179 | Favier et al. | Jun 2016 | A1 |
| 20160220794 | Negre | Aug 2016 | A1 |
| 20160256317 | Horvath et al. | Sep 2016 | A1 |
| 20160256318 | Horvath et al. | Sep 2016 | A1 |
| 20160256319 | Horvath et al. | Sep 2016 | A1 |
| 20160256320 | Horvath et al. | Sep 2016 | A1 |
| 20160287439 | Stergiopulos | Oct 2016 | A1 |
| 20160354244 | Horvath et al. | Dec 2016 | A1 |
| 20160354245 | Horvath et al. | Dec 2016 | A1 |
| 20170027582 | Khoury et al. | Feb 2017 | A1 |
| 20170071791 | Piven | Mar 2017 | A1 |
| 20170087016 | Camras | Mar 2017 | A1 |
| 20170172797 | Horvath et al. | Jun 2017 | A1 |
| 20170172798 | Horvath et al. | Jun 2017 | A1 |
| 20170172799 | Horvath | Jun 2017 | A1 |
| 20170312125 | Clauson et al. | Nov 2017 | A1 |
| 20170348149 | Stergiopulos et al. | Dec 2017 | A1 |
| 20170348150 | Horvath et al. | Dec 2017 | A1 |
| 20180014828 | Fonte et al. | Jan 2018 | A1 |
| 20180028361 | Haffner et al. | Feb 2018 | A1 |
| 20180092775 | de Juan, Jr. et al. | Apr 2018 | A1 |
| 20180147089 | Horvath et al. | May 2018 | A1 |
| 20180206878 | Uspenski et al. | Jul 2018 | A1 |
| 20180250166 | Lubatschowski | Sep 2018 | A1 |
| 20190000673 | Fjield et al. | Jan 2019 | A1 |
| 20190021907 | Horvath et al. | Jan 2019 | A1 |
| 20190038462 | Vandiest et al. | Feb 2019 | A1 |
| 20190046356 | Laroche | Feb 2019 | A1 |
| 20190060118 | Hill | Feb 2019 | A1 |
| 20190133826 | Horvath et al. | Mar 2019 | A1 |
| 20190121278 | Kawamura et al. | Apr 2019 | A1 |
| 20190142632 | Badawi et al. | May 2019 | A1 |
| 20190167475 | Horvath et al. | Jun 2019 | A1 |
| 20190240069 | Horvath et al. | Aug 2019 | A1 |
| 20190247231 | McClunan | Aug 2019 | A1 |
| 20190274881 | Romoda et al. | Sep 2019 | A1 |
| 20190274882 | Romoda et al. | Sep 2019 | A1 |
| 20190307608 | Lee et al. | Oct 2019 | A1 |
| 20190344057 | Cima et al. | Nov 2019 | A1 |
| 20190350758 | Horvath et al. | Nov 2019 | A1 |
| 20190353269 | Ossmer et al. | Nov 2019 | A1 |
| 20190358086 | Camras et al. | Nov 2019 | A1 |
| 20190374384 | Xie et al. | Dec 2019 | A1 |
| 20200069469 | Horvath et al. | Mar 2020 | A1 |
| 20200085620 | Euteneuer et al. | Mar 2020 | A1 |
| 20200121503 | Badawi et al. | Apr 2020 | A1 |
| 20200121504 | Stegmann et al. | Apr 2020 | A1 |
| 20200170839 | Borrmann et al. | Jun 2020 | A1 |
| 20200179171 | Crimaldi et al. | Jun 2020 | A1 |
| 20200214891 | Bigler et al. | Jul 2020 | A1 |
| 20200229977 | Mixter et al. | Jul 2020 | A1 |
| 20200229980 | Horvath | Jul 2020 | A1 |
| 20200229981 | Mixter et al. | Jul 2020 | A1 |
| 20200229982 | Mixter et al. | Jul 2020 | A1 |
| 20200246188 | Horvath et al. | Aug 2020 | A1 |
| 20200261271 | Horvath et al. | Aug 2020 | A1 |
| 20200276050 | Simons et al. | Sep 2020 | A1 |
| 20200306086 | Da Silva Curiel et al. | Oct 2020 | A1 |
| 20200345549 | Lu et al. | Nov 2020 | A1 |
| 20210015665 | Hacker et al. | Jan 2021 | A1 |
| 20210030590 | Blanda et al. | Feb 2021 | A1 |
| 20210038158 | Haffner et al. | Feb 2021 | A1 |
| 20210069486 | Hakim | Mar 2021 | A1 |
| 20210106462 | Sherwood et al. | Apr 2021 | A1 |
| 20210137736 | Cavuto et al. | May 2021 | A1 |
| 20210161713 | Bouremel et al. | Jun 2021 | A1 |
| 20210196516 | Ianchulev | Jul 2021 | A1 |
| 20210205132 | Horvath et al. | Jul 2021 | A1 |
| 20210212858 | Tran et al. | Jul 2021 | A1 |
| 20210251806 | Schultz et al. | Aug 2021 | A1 |
| 20210298948 | Haffner et al. | Sep 2021 | A1 |
| 20210315806 | Haffner | Oct 2021 | A1 |
| 20210330499 | Wardle et al. | Oct 2021 | A1 |
| 20220087865 | Argento et al. | Mar 2022 | A1 |
| 20220160545 | Mixter et al. | May 2022 | A1 |
| 20220160546 | Mixter et al. | May 2022 | A1 |
| 20220202613 | Chang et al. | Jun 2022 | A1 |
| Number | Date | Country |
|---|---|---|
| 2014201621 | Mar 2016 | AU |
| 2016201445 | Mar 2016 | AU |
| 2018200325 | Feb 2018 | AU |
| 2017274654 | Dec 2018 | AU |
| 2020201818 | Apr 2020 | AU |
| 2017439185 | May 2020 | AU |
| 2018412569 | Oct 2020 | AU |
| 112017025859 | Aug 2018 | BR |
| 112020008969 | Oct 2020 | BR |
| 2987953 | Dec 2016 | CA |
| 3080713 | May 2019 | CA |
| 3093160 | Sep 2019 | CA |
| 108743016 | Nov 2018 | CN |
| 111405875 | Jul 2020 | CN |
| 2020011460 | Nov 2020 | CO |
| 10217061 | Mar 2003 | DE |
| 102010015447 | Oct 2011 | DE |
| 102017124885 | Apr 2019 | DE |
| 102018112065 | Nov 2019 | DE |
| 102019204846 | Oct 2020 | DE |
| 1292256 | Mar 2003 | EP |
| 1737531 | Jan 2007 | EP |
| 3302381 | Apr 2018 | EP |
| 1765234 | Oct 2019 | EP |
| 2999430 | Nov 2019 | EP |
| 2677981 | Apr 2020 | EP |
| 3659495 | Jun 2020 | EP |
| 3518846 | Aug 2020 | EP |
| 3666236 | Aug 2020 | EP |
| 3687374 | Aug 2020 | EP |
| 3706653 | Sep 2020 | EP |
| 3730104 | Oct 2020 | EP |
| 3735947 | Nov 2020 | EP |
| 3773377 | Feb 2021 | EP |
| 3846747 | Jul 2021 | EP |
| 3846748 | Jul 2021 | EP |
| 3329884 | Aug 2021 | EP |
| 2389138 | Sep 2021 | EP |
| 3870120 | Sep 2021 | EP |
| 3313335 | Nov 2021 | EP |
| 2725550 | Sep 2019 | ES |
| 1252748 | May 2019 | HK |
| E043303 | Aug 2019 | HU |
| 5576427 | Aug 2014 | JP |
| 2018519892 | Jul 2018 | JP |
| 2018130580 | Aug 2018 | JP |
| 2019517366 | Jun 2019 | JP |
| 2019205934 | Dec 2019 | JP |
| 2020049361 | Apr 2020 | JP |
| 2018015684 | Feb 2018 | KR |
| 20190019966 | Feb 2019 | KR |
| 20200021551 | Feb 2020 | KR |
| 20200059305 | May 2020 | KR |
| 2640455 | Aug 2019 | PL |
| 2640455 | May 2019 | PT |
| 2687764 | May 2019 | RU |
| 2018142990 | Jun 2020 | RU |
| 11202008604 | Oct 2020 | SG |
| 201906873 | Jun 2019 | TR |
| WO9219294 | Nov 1992 | WO |
| WO2020231993 | Nov 2002 | WO |
| WO2004081613 | Sep 2004 | WO |
| WO2007011302 | Jan 2007 | WO |
| WO2010111528 | Sep 2010 | WO |
| WO2014130574 | Aug 2014 | WO |
| WO2016149425 | Sep 2016 | WO |
| WO2016196841 | Dec 2016 | WO |
| WO2018229766 | Dec 2018 | WO |
| WO2019018807 | Jan 2019 | WO |
| WO2019094004 | May 2019 | WO |
| WO2019165053 | Aug 2019 | WO |
| WO2019172940 | Sep 2019 | WO |
| WO2020150663 | Jul 2020 | WO |
| WO20200215068 | Oct 2020 | WO |
| WO202022391 | Nov 2020 | WO |
| WO2020247365 | Dec 2020 | WO |
| WO2020261184 | Dec 2020 | WO |
| WO2021007294 | Jan 2021 | WO |
| WO2021007296 | Jan 2021 | WO |
| WO2021028703 | Feb 2021 | WO |
| WO2021068078 | Apr 2021 | WO |
| WO2021072315 | Apr 2021 | WO |
| WO2021072317 | Apr 2021 | WO |
| WO2021113730 | Jun 2021 | WO |
| WO2021142255 | Jul 2021 | WO |
| WO2021151007 | Jul 2021 | WO |
| WO2021163566 | Aug 2021 | WO |
| WO2021168130 | Aug 2021 | WO |
| WO2021174298 | Sep 2021 | WO |
| WO2021176332 | Sep 2021 | WO |
| WO2021188952 | Sep 2021 | WO |
| WO202104312 | Oct 2021 | WO |
| WO2021212007 | Oct 2021 | WO |
| WO2021230887 | Nov 2021 | WO |
| 201708295 | May 2020 | ZA |
| Entry |
|---|
| International Search Report and Written Opinion received for International PCT Application No. PCT/US2021/014774, filed on Jan. 22, 2021; Applicant: Shifamed Holdings, LLC; dated May 12, 2021, 10 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US18/43158, filed on Jul. 20, 2018, Applicant: Shifamed Holdings, LLC, dated Nov. 23, 2018, 12 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US20/41159, filed on Jul. 8, 2020, Applicant: Shifamed Holdings, LLC, dated Oct. 28, 2020, 13 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US20/41152, filed on Jul. 8, 2020, Applicant: Shifamed Holdings, LLC, dated Oct. 28, 2020, 13 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US20/14186, filed on Jan. 17, 2020, Applicant: Shifamed Holdings, LLC, dated Jun. 4, 2020, 13 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/17962, filed on Feb. 12, 2021, Applicant: Shifamed Holdings, LLC, dated Jun. 7, 2021, 12 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/23238, filed on Mar. 19, 2021, Applicant: Shifamed Holdings, LLC, dated Jul. 8, 2021, 10 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/18601, filed on Feb. 18, 2021, Applicant: Shifamed Holdings, LLC, dated Jul. 19, 2021, 12 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/27742, filed on Apr. 16, 2021, Applicant: Shifamed Holdings, LLC, dated Oct. 7, 2021, 13 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US20/55144, filed on Oct. 9, 2020, Applicant: Shifamed Holdings, LLC, dated Feb. 1, 2021, 16 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US20/55141, filed on Oct. 9, 2020, Applicant: Shifamed Holdings, LLC, dated Jan. 29, 2021, 11 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/49140, filed on Sep. 3, 2021, Applicant: Shifamed Holdings, LLC, dated Dec. 7, 2021, 22 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US21/55258, filed on Oct. 15, 2021, Applicant: Shifamed Holdings, LLC, dated Feb. 28, 2022, 18 pages. |
| International Search Report and Written Opinion received for PCT Application No. PCT/US22/13336, filed on Jan. 21, 2022, Applicant: Shifamed Holdings, LLC, dated Apr. 11, 2022, 9 pages. |
| Number | Date | Country | |
|---|---|---|---|
| 20220142818 A1 | May 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62965117 | Jan 2020 | US |
