US20190021907A1 - Intrascleral shunt placement - Google Patents

Abstract

Glaucoma can be treated by implanting an intraocular shunt into an eye. The eye has an anterior chamber and sclera. A shunt can be placed into the eye to establish fluid communication from the anterior chamber of the eye through the sclera, and a pharmaceutical or biological agent can be administered to the eye.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• This application is a continuation of U.S. patent Ser. No. 15/158,368, filed May 18, 2016, which is a continuation-in-part of U.S. patent application Ser. No. 15/005,954, filed Jan. 25, 2016, which is a continuation of U.S. patent Ser. No. 14/508,938, filed Oct. 7, 2014, now U.S. Pat. No. 9,271,869, which is a continuation of U.S. patent application Ser. No. 13/314,939, filed Dec. 8, 2011, now U.S. Pat. No. 8,852,136; this application is also a continuation-in-part of U.S. patent application Ser. No. 13/778,873, filed Feb. 27, 2013; this application is also a continuation-in-part of U.S. patent application Ser. No. 14/317,676, filed Jun. 27, 2014, which claims the priority benefit of U.S. Provisional Patent App. No. 61/841,224, filed on Jun. 28, 2013, and U.S. Provisional Patent App. No. 61/895,341, filed on Oct. 24, 2013; the entirety of each of which is incorporated by reference herein.
FIELD OF THE INVENTIONS
• The present inventions generally relate to devices for reducing intraocular pressure by creating a drainage pathway between the anterior chamber of the eye and the intrascleral space.
BACKGROUND
• Glaucoma is a disease in which the optic nerve is damaged, leading to progressive, irreversible loss of vision. It is typically associated with increased pressure of the fluid (i.e., aqueous humor) in the eye. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness. Once lost, this damaged visual field cannot be recovered. Glaucoma is the second leading cause of blindness in the world, affecting 1 in 200 people under the age of fifty, and 1 in 10 over the age of eighty for a total of approximately 70 million people worldwide.
• The importance of lowering intraocular pressure (IOP) in delaying glaucomatous progression has been well documented. When drug therapy fails, or is not tolerated, surgical intervention is warranted. Surgical filtration methods for lowering intraocular pressure by creating a fluid flow-path between the anterior chamber and the subconjunctival tissue have been described. One particular ab interno glaucoma filtration method has been described whereby an intraocular shunt is implanted by directing a needle which holds the shunt through the cornea, across the anterior chamber, and through the trabecular meshwork and sclera, and into the subconjunctival space. See, for example, U.S. Pat. No. 6,544,249, U.S. Patent Pub. No. 2008/0108933, and U.S. Pat. No. 6,007,511.
• Proper positioning of a shunt in the subconjunctival space is critical in determining the success or failure of subconjunctival glaucoma filtration surgery for a number of reasons. In particular, the location of the shunt has been shown to play a role in stimulating the formation of active drainage structures such as veins or lymph vessels. See, for example, U.S. Patent Pub. No. 2008/0108933. In addition, it has been suggested that the conjunctiva itself plays a critical role in glaucoma filtration surgery. A healthy conjunctiva allows drainage channels to form and less opportunity for inflammation and scar tissue formation, which are frequent causes of failure in subconjunctival filtration surgery. See, for example, Yu et al., Progress in Retinal and Eye Research, 28: 303-328 (2009).
SUMMARY
• According to some embodiments, methods and devices are provided for positioning an intraocular shunt within the eye to treat glaucoma. Various methods are disclosed herein which allow a clinician to create a fluid pathway from the anterior chamber to an area of lower pressure within the eye. Although methods may be discussed in the context of positioning an outflow end of a shunt in a particular location (e.g., between layers of Tenon's capsule), the methods disclosed herein can be used to create a fluid pathway in which the outflow end of the shunt is positioned in other areas of low pressure, such as the supraciliary space, suprachoroidal space, the intrascleral space (i.e., between layers of sclera), intra-Tenon's adhesion space (i.e., between layers of Tenon's capsule), or subconjunctival space.
• In some embodiments, the present inventions also provide methods for implanting intraocular shunts in the intrascleral space. For example, in some embodiments, methods can be performed to avoid contact between the shunt and/or delivery device with the conjunctiva. Intrascleral shunt placement safeguards the integrity of the conjunctiva to allow subconjunctival drainage pathways to successfully form. Additionally, the intrascleral space is less prone to fibrosis than the subconjunctival space and placement in the intrascleral space eliminates the risk of hypotony and related side effects.
• Methods of some embodiments involve inserting into the eye a hollow shaft configured to hold an intraocular shunt, deploying the shunt from the hollow shaft such that the shunt forms a passage from the anterior chamber of the eye to the intrascleral space of the eye, and withdrawing the hollow shaft from the eye. The implanted shunt allows drainage of aqueous humor from an anterior chamber of the eye into the episcleral vessel complex, a traditional fluid drainage channel. Such placement also allows diffusion of fluid into the subconjunctival and suprachoroidal spaces.
• The intraocular shunts used with methods of some embodiments define a hollow body including an inlet and an outlet, and the hollow body is configured to form a passage from the anterior chamber of the eye to the intrascleral space. In particular, the hollow body has a length sufficient to provide a passageway between the anterior chamber and the intrascleral space.
• In certain aspects, some embodiments generally provide shunts composed of a material that has an elasticity modulus that is compatible with an elasticity modulus of tissue surrounding the shunt. In this manner, shunts of some embodiments are flexibility matched with the surrounding tissue, and thus will remain in place after implantation without the need for any type of anchor that interacts with the surrounding tissue. Consequently, shunts of some embodiments will maintain fluid flow away for an anterior chamber of the eye after implantation without causing irritation or inflammation to the tissue surrounding the eye.
• In other aspects, some embodiments generally provide shunts in which a portion of the shunt is composed of a flexible material that is reactive to pressure, i.e., an inner diameter of the shunt fluctuates depending upon the pressures exerted on that portion of the shunt. Thus, the flexible portion of the shunt acts as a valve that regulates fluid flow through the shunt. After implantation, intraocular shunts have pressure exerted upon them by tissues surrounding the shunt (e.g., scleral tissue) and pressure exerted upon them by aqueous humor flowing through the shunt. When the pressure exerted on the flexible portion of the shunt by the surrounding tissue is greater than the pressure exerted on the flexible portion of the shunt by the fluid flowing through the shunt, the flexible portion decreases in diameter, restricting flow through the shunt. The restricted flow results in aqueous humor leaving the anterior chamber at a reduced rate.
• When the pressure exerted on the flexible portion of the shunt by the fluid flowing through the shunt is greater than the pressure exerted on the flexible portion of the shunt by the surrounding tissue, the flexible portion increases in diameter, increasing flow through the shunt. The increased flow results in aqueous humor leaving the anterior chamber at an increased rate.
• The flexible portion of the shunt may be any portion of the shunt. In certain embodiments, the flexible portion is a distal portion of the shunt. In certain embodiments, the entire shunt is composed of the flexible material.
• Other aspects of some embodiments generally provide multi-port shunts. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt even if one or more ports of the shunt become clogged with particulate. In certain embodiments, the shunt includes a hollow body defining a flow path and more than two ports, in which the body is configured such that a proximal portion receives fluid from the anterior chamber of an eye and a distal portion directs the fluid to a location of lower pressure with respect to the anterior chamber.
• The shunt may have many different configurations. In certain embodiments, the proximal portion of the shunt (i.e., the portion disposed within the anterior chamber of the eye) includes more than one port and the distal portion of the shunt (i.e., the portion that is located in the intrascleral space) includes a single port. In other embodiments, the proximal portion includes a single port and the distal portion includes more than one port. In still other embodiments, the proximal and the distal portions include more than one port.
• The ports may be positioned in various different orientations and along various different portions of the shunt. In certain embodiments, at least one of the ports is oriented at an angle to the length of the body. In certain embodiments, at least one of the ports is oriented 90° to the length of the body.
• The ports may have the same or different inner diameters. In certain embodiments, at least one of the ports has an inner diameter that is different from the inner diameters of the other ports.
• Other aspects of some embodiments generally provide shunts with overflow ports. Those shunts are configured such that the overflow port remains closed until there is a pressure build-up within the shunt sufficient to force open the overflow port. Such pressure build-up typically results from particulate partially or fully clogging an entry or an exit port of the shunt. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt by the overflow port even if one port of the shunt becomes clogged with particulate.
• In certain embodiments, the shunt includes a hollow body defining an inlet configured to receive fluid from an anterior chamber of the eye and an outlet configured to direct the fluid to a location of lower pressure with respect to the anterior chamber, the body further including at least one slit. The slit may be located at any place along the body of the shunt. In certain embodiments, the slit is located in proximity to the inlet. In other embodiments, the slit is located in proximity to the outlet. In certain embodiments, there is a slit in proximity to both the inlet and the outlet of the shunt.
• In certain embodiments, the slit has a width that is substantially the same or less than an inner diameter of the inlet. In other embodiments, the slit has a width that is substantially the same or less than an inner diameter of the outlet. Generally, the slit does not direct the fluid unless the outlet is obstructed. However, the shunt may be configured such that the slit does direct at least some of the fluid even if the inlet or outlet is not obstructed.
• In other aspects, some embodiments generally provide a shunt having a variable inner diameter. In some embodiments, the diameter increases from inlet to outlet of the shunt. By having a variable inner diameter that increases from inlet to outlet, a pressure gradient is produced and particulate that may otherwise clog the inlet of the shunt is forced through the inlet due to the pressure gradient. Further, the particulate will flow out of the shunt because the diameter only increases after the inlet.
• In certain embodiments, the shunt includes a hollow body defining a flow path and having an inlet configured to receive fluid from an anterior chamber of an eye and an outlet configured to direct the fluid to the intrascleral space, in which the body further includes a variable inner diameter that increases along the length of the body from the inlet to the outlet. In certain embodiments, the inner diameter continuously increases along the length of the body. In other embodiments, the inner diameter remains constant along portions of the length of the body. The shunts discussed above and herein are described relative to the eye and, more particularly, in the context of treating glaucoma and solving the above identified problems relating to intraocular shunts. Nonetheless, it will be appreciated that shunts described herein may find application in any treatment of a body organ requiring drainage of a fluid from the organ and are not limited to the eye.
• In other aspects, some embodiments generally provide shunts for facilitating conduction of fluid flow away from an organ, the shunt including a body, in which at least one end of the shunt is shaped to have a plurality of prongs. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt by any space between the prongs even if one portion of the shunt becomes clogged with particulate.
• The shunt may have many different configurations. In certain embodiments, the proximal end of the shunt (i.e., the portion disposed within the anterior chamber of the eye) is shaped to have the plurality of prongs. In other embodiments, the distal end of the shunt (i.e., the portion that is located in an area of lower pressure with respect to the anterior chamber such as the intrascleral space) is shaped to have the plurality of prongs. In other embodiments, both a proximal end and a distal end of the shunt are shaped to have the plurality of prongs. In some embodiments, the shunt is a soft gel shunt.
• In other aspects, some embodiments generally provide a shunt for draining fluid from an anterior chamber of an eye that includes a hollow body defining an inlet configured to receive fluid from an anterior chamber of the eye and an outlet configured to direct the fluid to a location of lower pressure with respect to the anterior chamber; the shunt being configured such that at least one end of the shunt includes a longitudinal slit. Such shunts reduce probability of the shunt clogging after implantation because the end(s) of the shunt can more easily pass particulate which would generally clog a shunt lacking the slits.
• The shunt may have many different configurations. In certain embodiments, the proximal end of the shunt (i.e., the portion disposed within the anterior chamber of the eye) includes a longitudinal slit. In other embodiments, the distal end of the shunt (i.e., the portion that is located in an area of lower pressure with respect to the anterior chamber such as intrascleral space) includes a longitudinal slit. In other embodiments, both a proximal end and a distal end of the shunt includes a longitudinal slit. In some embodiments, the shunt is a soft gel shunt.
• In certain embodiments, shunts of some embodiments may be coated or impregnated with at least one pharmaceutical and/or biological agent or a combination thereof. The pharmaceutical and/or biological agent may coat or impregnate an entire exterior of the shunt, an entire interior of the shunt, or both. Alternatively, the pharmaceutical and/or biological agent may coat and/or impregnate a portion of an exterior of the shunt, a portion of an interior of the shunt, or both. Methods of coating and/or impregnating an intraocular shunt with a pharmaceutical and/or biological agent are known in the art. See for example, Darouiche (U.S. U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283; 5,853,745; and 5,624,704) and Yu et al. (U.S. Patent Pub. No. 2008/0108933). The content of each of these references is incorporated by reference herein its entirety.
• In certain embodiments, the exterior portion of the shunt that resides in the anterior chamber after implantation (e.g., about 1 mm of the proximal end of the shunt) is coated and/or impregnated with the pharmaceutical or biological agent. In other embodiments, the exterior of the shunt that resides in the scleral tissue after implantation of the shunt is coated and/or impregnated with the pharmaceutical or biological agent. In other embodiments, the exterior portion of the shunt that resides in the area of lower pressure (e.g., the intrascleral space) after implantation is coated and/or impregnated with the pharmaceutical or biological agent. In embodiments in which the pharmaceutical or biological agent coats and/or impregnates the interior of the shunt, the agent may be flushed through the shunt and into the area of lower pressure (e.g., the intrascleral space).
• Any pharmaceutical and/or biological agent or combination thereof may be used with shunts of some embodiments. The pharmaceutical and/or biological agent may be released over a short period of time (e.g., seconds) or may be released over longer periods of time (e.g., days, weeks, months, or even years). Exemplary agents include anti-mitotic pharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen, Avastin, VEGF or steroids).
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 provides a cross-sectional diagram of the general anatomy of the eye.
• FIG. 2 provides another cross-sectional view the eye, and certain anatomical structures of the eye along with an implanted intraocular shunt.
• FIG. 3 depicts, implantation of an intraocular shunt with a distal end of a deployment device holding a shunt, shown in cross-section.
• FIG. 4 depicts an example of a hollow shaft configured to hold an intraocular shunt.
• FIG. 5A depicts the tip bevel portion of a triple-ground needle tip.FIG. 5B depicts the flat bevel portion of a triple-ground needle tip.FIG. 5C depicts an intraocular shunt within a triple-ground needle tip.
• FIG. 6 provides a schematic of a shunt having a flexible portion.
• FIGS. 7A, 7B and 7C provide schematics of a shunt implanted into an eye for regulation of fluid flow from the anterior chamber of the eye to a drainage structure of the eye.
• FIGS. 8A-8C show different embodiments of multi-port shunts.FIG. 8A shows an embodiment of a shunt in which the proximal portion of the shunt includes more than one port and the distal portion of the shunt includes a single port.FIG. 8B shows another embodiment of a shunt in which the proximal portion includes a single port and the distal portion includes more than one port.FIG. 8C shows another embodiment of a shunt in which the proximal portions include more than one port and the distal portions include more than one port.
• FIGS. 9A and 9B show different embodiments of multi-port shunts having different diameter ports.
• FIGS. 10A-10C provide schematics of shunts having a slit located along a portion of the length of the shunt.
• FIG. 11 depicts a shunt having multiple slits along a length of the shunt.
• FIG. 12 depicts a shunt having a slit at a proximal end of the shunt.
• FIG. 13 provides a schematic of a shunt that has a variable inner diameter.
• FIGS. 14A-14D depict a shunt having multiple prongs at a distal and/or proximal end.
• FIGS. 15A-15D depict a shunt having a longitudinal slit at a distal and/or proximal end.
• FIG. 16 is a schematic showing an embodiment of a shunt deployment device according to some embodiments.
• FIG. 17 shows an exploded view of the device shown inFIG. 16.
• FIGS. 18A-18D are schematics showing different enlarged views of the deployment mechanism of the deployment device.
• FIGS. 19A-19C are schematics showing interaction of the deployment mechanism with a portion of the housing of the deployment device.
• FIG. 20 shows a cross sectional view of the deployment mechanism of the deployment device.
• FIGS. 21A and 21B show schematics of the deployment mechanism in a pre-deployment configuration.FIG. 21C shows an enlarged view of the distal portion of the deployment device ofFIG. 21A. This figure shows an intraocular shunt loaded within a hollow shaft of the deployment device.
• FIGS. 22A and 22B show schematics of the deployment mechanism at the end of the first stage of deployment of the shunt from the deployment device.FIG. 22C shows an enlarged view of the distal portion of the deployment device ofFIG. 22A. This figure shows an intraocular shunt partially deployed from within a hollow shaft of the deployment device.
• FIG. 23A shows a schematic of the deployment device after deployment of the shunt from the device.FIG. 23B show a schematic of the deployment mechanism at the end of the second stage of deployment of the shunt from the deployment device.FIG. 23C shows an enlarged view of the distal portion of the deployment device after retraction of the shaft with the pusher abutting the shunt.FIG. 23D shows an enlarged view of the distal portion of the deployment device after deployment of the shunt.
• FIGS. 24-31 depict a sequence for ab interno shunt placement, according to some embodiments.
• FIG. 32 depicts an implanted shunt in an S-shaped scleral passageway, according to some embodiments.
• FIGS. 33-39 depict a sequence for ab externo shunt placement, according to some embodiments.
• FIGS. 40-41 depict a sequence for ab externo insertion of a shaft of a deployment device using an applicator, according to some embodiments.
• FIG. 42 depicts deployment of the shunt in the intra scleral space where a distal end of the shunt is flush with the sclera surface, according to some embodiments.
• FIG. 43 depicts deployment of the shunt in the intra scleral space where a distal end of the shunt is about 200-500 microns behind the scleral exit, according to some embodiments.
• FIG. 44 depicts deployment of the shunt in the intra scleral space where a distal end of the shunt is more than about 500 microns behind the scleral exit, according to some embodiments.
DETAILED DESCRIPTION
• FIG. 1 provides a schematic diagram of the general anatomy of the eye. An anterior aspect of theanterior chamber1 of the eye is thecornea2, and a posterior aspect of theanterior chamber1 of the eye is the iris4. Beneath the iris4 is thelens5. Theanterior chamber1 is filled withaqueous humor3. Theaqueous humor3 drains into a space(s)6 below theconjunctiva7 through the trabecular meshwork (not shown in detail) of thesclera8. The aqueous humor is drained from the space(s)6 below theconjunctiva7 through a venous drainage system (not shown).
• FIG. 2 provides a cross-sectional view of a portion of the eye, and provides greater detail regarding certain anatomical structures of the eye. In particular,FIG. 2 shows ashunt12 implanted in the sclera8 (i.e., intrascleral implantation). Placement ofshunt12 within thesclera8 allowsaqueous humor3 to drain into traditional fluid drainage channels of the eye (e.g., theintrascleral vein9, thecollector channel10, Schlemm'scanal11, thetrabecular outflow13a, and theuveoscleral outflow13bto theciliary muscle14.
• In conditions of glaucoma, the pressure of the aqueous humor in the eye (anterior chamber) increases and this resultant increase of pressure can cause damage to the vascular system at the back of the eye and especially to the optic nerve. The treatment of glaucoma and other diseases that lead to elevated pressure in the anterior chamber involves relieving pressure within the anterior chamber to a normal level.
• Glaucoma filtration surgery is a surgical procedure typically used to treat glaucoma. The procedure involves placing a shunt in the eye to relieve intraocular pressure by creating a pathway for draining aqueous humor from the anterior chamber of the eye. The shunt is typically positioned in the eye such that it creates a drainage pathway between the anterior chamber of the eye and a region of lower pressure. Various structures and/or regions of the eye having lower pressure that have been targeted for aqueous humor drainage include Schlemm's canal, the subconjunctival space, the episcleral vein, the suprachoroidal space, or the subarachnoid space. Methods of implanting intraocular shunts are known in the art. Shunts may be implanted using an ab externo approach (entering through the conjunctiva and inwards through the sclera) or an ab interno approach (entering through the cornea, across the anterior chamber, through the trabecular meshwork and sclera).
• Ab interno approaches for implanting an intraocular shunt in the subconjunctival space are shown for example in Yu et al. (U.S. Pat. No. 6,544,249 and U.S. patent publication number 2008/0108933) and Prywes (U.S. Pat. No. 6,007,511), the contents of each of which are incorporated by reference herein in its entirety. Briefly and with reference toFIG. 3, a surgical intervention to implant the shunt involves inserting into the eye adeployment device15 that holds an intraocular shunt, and deploying the shunt within theeye16. Adeployment device15 holding the shunt enters theeye16 through the cornea17 (ab interno approach). Thedeployment device15 is advanced across the anterior chamber20 (as depicted by the broken line) in what is referred to as a transpupil implant insertion. Thedeployment device15 is advanced through the sclera21 until a distal portion of the device is in proximity to the subconjunctival space. The shunt is then deployed from the deployment device, producing a conduit between the anterior chamber and the subconjunctival space to allow aqueous humor to drain through the conjunctival lymphatic system.
• While such ab interno subconjunctival filtration procedures have been successful in relieving intraocular pressure, there is a substantial risk that the intraocular shunt may be deployed too close to the conjunctiva, resulting in irritation and subsequent inflammation and/or scarring of the conjunctiva, which can cause the glaucoma filtration procedure to fail (See Yu et al., Progress in Retinal and Eye Research, 28: 303-328 (2009)). Additionally, commercially available shunts that are currently utilized in such procedures are not ideal for ab interno subconjunctival placement due to the length of the shunt (i.e., too long) and/or the materials used to make the shunt (e.g., gold, polymer, titanium, or stainless steel), and can cause significant irritation to the tissue surrounding the shunt, as well as the conjunctiva, if deployed too close.
• Some embodiments of the present inventions provide methods for implanting intraocular shunts within the sclera (i.e., intrascleral implantation) and are thus suitable for use in an ab interno glaucoma filtration procedure. In methods of some embodiments, the implanted shunt forms a passage from the anterior chamber of the eye into the sclera (i.e., intrascleral space). Design and/or deployment of an intraocular shunt such that the inlet terminates in the anterior chamber and the outlet terminates intrascleral safeguards the integrity of the conjunctiva to allow subconjunctival drainage pathways to successfully form. Additionally, drainage into the intrascleral space provides access to more lymphatic channels than just the conjunctival lymphatic system, such as the episcleral lymphatic network. Moreover, design and/or deployment of an intraocular shunt such that the outlet terminates in the intrascleral space avoids having to pierce Tenon's capsule which can otherwise cause complications during glaucoma filtration surgery due to its tough and fibrous nature.
Methods for Intrascleral Shunt Placement
• The methods of some embodiments involve inserting into the eye a hollow shaft configured to hold an intraocular shunt. In certain embodiments, the hollow shaft is a component of a deployment device that may deploy the intraocular shunt. The shunt is then deployed from the shaft into the eye such that the shunt forms a passage from the anterior chamber into the sclera (i.e., the intrascleral space). The hollow shaft is then withdrawn from the eye.
• Referring toFIG. 2, which show an intraocular shunt placed into the eye such that the shunt forms a passage for fluid drainage from the anterior chamber to the intrascleral space. To place the shunt within the eye, a surgical intervention to implant the shunt is performed that involves inserting into the eye a deployment device that holds an intraocular shunt, and deploying at least a portion of the shunt within intrascleral space. In certain embodiments, a hollow shaft of a deployment device holding the shunt enters the eye through the cornea (ab interno approach). The shaft is advanced across the anterior chamber in what is referred to as a transpupil implant insertion. The shaft is advanced into thesclera8 until a distal portion of the shaft is in proximity to thetrabecular outflow13b. Insertion of the shaft of the deployment device into thesclera8 produces a long scleral channel of about 3 mm to about 5 mm in length. Withdrawal of the shaft of the deployment device prior to deployment of theshunt12 from the device produces a space in which theshunt12 may be deployed. Deployment of theshunt12 allows foraqueous humor3 to drain into traditional fluid drainage channels of the eye (e.g., theintrascleral vein9, thecollector channel10, Schlemm'scanal11, thetrabecular outflow13a, and theuveoscleral outflow13bto theciliary muscle14.
• FIG. 4 provides an exemplary schematic of a hollow shaft for use in accordance with the methods of some embodiments of the methods disclosed herein. This figure shows ahollow shaft22 that is configured to hold anintraocular shunt23. The shaft may hold the shunt within thehollow interior24 of the shaft, as is shown inFIG. 4. Alternatively, the hollow shaft may hold the shunt on anouter surface25 of the shaft. In some embodiments, the shunt is held completely within the hollow interior of theshaft24, as is shown inFIG. 4. In other embodiments, ashunt23ais only partially disposed within ahollow shaft23b, as shown inFIG. 5A. Generally, in one embodiment, the intraocular shunts are of a cylindrical shape and have an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter of about 10 μm to about 250 μm, an outside diameter of about 100 μm to about 450 μm, and a length of about 1 mm to about 12 mm. In some embodiments, the shunt has a length of about 2 mm to about 10 mm and an outside diameter of about 150 μm to about 400 μm. Thehollow shaft22 is configured to at least hold a shunt of such shape and such dimensions. However, thehollow shaft22 may be configured to hold shunts of different shapes and different dimensions than those described above, and some embodiments can encompass ashaft22 that may be configured to hold any shaped or dimensioned intraocular shunt.
• Preferably, the methods of some embodiments are conducted by making an incision in the eye prior to insertion of the deployment device. Although in some embodiments, the methods of some embodiments may be conducted without making an incision in the eye prior to insertion of the deployment device. In certain embodiments, the shaft that is connected to the deployment device has a sharpened point or tip. In certain embodiments, the hollow shaft is a needle. Exemplary needles that may be used are commercially available from Terumo Medical Corp. (Elkington, Md.). In some embodiments, the needle has a hollow interior and a beveled tip, and the intraocular shunt is held within the hollow interior of the needle. In some embodiments, the needle has a hollow interior and a triple ground point or tip.
• The methods of some embodiments are preferably conducted without needing to remove an anatomical portion or feature of the eye, including but not limited to the trabecular meshwork, the iris, the cornea, or aqueous humor. The methods of some embodiments are also preferably conducted without inducing substantial ocular inflammation, such as subconjunctival blebbing or endophthalmitis. Such methods can be achieved using an ab interno approach by inserting the hollow shaft configured to hold the intraocular shunt through the cornea, across the anterior chamber, through the trabecular meshwork and into the sclera. However, the methods of some embodiments may be conducted using an ab externo approach.
• Some embodiments of the methods disclosed herein can be performed such that the inserting step can further comprise the step of injecting an aqueous solution into the eye. For example, an aqueous solution can be injected below Tenon's capsule. The inserting step can also comprise ab interno insertion of the hollow shaft into the eye. Ab interno insertion can comprise inserting the hollow shaft into the eye above the corneal limbus. Ab interno insertion can comprise inserting the hollow shaft into the eye below the corneal limbus.
• For example, when the methods of some embodiments are conducted using an ab interno approach, the angle of entry through the cornea affects optimal placement of the shunt in the intrascleral space. Preferably, the hollow shaft is inserted into the eye at an angle above or below the corneal limbus, in contrast with entering through the corneal limbus. For example, the hollow shaft is inserted approximately 0.25 to 3.0 mm, preferably approximately 0.5 to 2.5 mm, more preferably approximately 1.0 mm to 2.0 mm above the corneal limbus, or any specific value within said ranges, e.g., approximately 1.0 mm, approximately 1.1 mm, approximately 1.2 mm, approximately 1.3 mm, approximately 1.4 mm, approximately 1.5 mm, approximately 1.6 mm, approximately 1.7 mm, approximately 1.8 mm, approximately 1.9 mm or approximately 2.0 mm above the corneal limbus.
• Without intending to be bound by any theory, placement of the shunt farther from the limbus at the exit site, as provided by an angle of entry above the limbus, is believed to provide access to more lymphatic channels for drainage of aqueous humor, such as the episcleral lymphatic network, in addition to the conjunctival lymphatic system. A higher angle of entry also results in flatter placement in the intrascleral space so that there is less bending of the shunt.
• In certain embodiments, to ensure proper positioning and functioning of the intraocular shunt, the depth of penetration into the sclera is important when conducting the methods of some embodiments. In one embodiment, the distal tip of the hollow shaft pierces the sclera without coring, removing or causing major tissue distortion of the surrounding eye tissue. The shunt is then deployed from the shaft. Preferably, a distal portion of the hollow shaft (as opposed to the distal tip) completely enters the sclera before the shunt is deployed from the hollow shaft. In certain embodiments, the hollow shaft is a flat bevel needle, such as a needle having a triple-ground point. The tip bevel first pierces through the sclera making a horizontal slit. In a preferred embodiment of the methods of some embodiments, the needle is advanced even further such that the entire flat bevel penetrates into the sclera, to spread and open the tissue to a full circular diameter. Thetip bevel portion190 andflat bevel portion192 of a triple ground needle point, and the configuration of theshunt194 disposed in the needle point, are exemplified as the gray shaded areas inFIGS. 5A-5C. Without intending to be bound by any theory, if the scleral channel is not completely forced open by the flat bevel portion of the needle, the material around the opening may not be sufficiently stretched and a pinching of the implant in that zone will likely occur, causing the shunt to fail. Full entry of the flat bevel into the sclera causes minor distortion and trauma to the local area. However, this area ultimately surrounds and conforms to the shunt once the shunt is deployed in the eye.
Intraocular Shunts
• Some embodiments of the present inventions provide intraocular shunts that are configured to form a drainage pathway from the anterior chamber of the eye to the intrascleral space. In particular, the intraocular shunts of some embodiments have a length that is sufficient to form a drainage pathway from the anterior chamber of the eye to the intrascleral space. The length of the shunt is important for achieving placement specifically in the intrascleral space. A shunt that is too long will extend beyond the intrascleral space and irritate the conjunctiva which can cause the filtration procedure to fail, as previously described. A shunt that is too short will not provide sufficient access to drainage pathways such as the episcleral lymphatic system or the conjunctival lymphatic system.
• Shunts of some embodiments may be any length that allows for drainage of aqueous humor from an anterior chamber of an eye to the intrascleral space. Exemplary shunts range in length from approximately 2 mm to approximately 10 mm or between approximately 4 mm to approximately 8 mm, or any specific value within said ranges. In certain embodiments, the length of the shunt is between approximately 6 to 8 mm, or any specific value within said range, e.g., 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 mm, or 8.0 mm.
• The intraocular shunts of some embodiments are particularly suitable for use in an ab interno glaucoma filtration procedure. Commercially available shunts that are currently used in ab interno filtration procedures are typically made of a hard, inflexible material such as gold, polymer, titanium, or stainless steel, and cause substantial irritation of the eye tissue, resulting in ocular inflammation such as subconjunctival blebbing or endophthalmitis. The methods of some embodiments may be conducted using any commercially available shunts, such as the Optonol Ex-PRESS™ mini Glaucoma shunt, and the Solx DeepLight Gold™ Micro-Shunt.
• In some embodiments, the intraocular shunts of some embodiments are flexible, and have an elasticity modulus that is substantially identical to the elasticity modulus of the surrounding tissue in the implant site. As such, the intraocular shunts of some embodiments are easily bendable, do not erode or cause a tissue reaction, and do not migrate once implanted. Thus, when implanted in the eye using an ab interno procedure, such as the methods described herein, the intraocular shunts of some embodiments do not induce substantial ocular inflammation such as subconjunctival blebbing or endophthalmitis. Additional exemplary features of the intraocular shunts of some embodiments are discussed in further detail below.
Tissue Compatible Shunts
• In certain aspects, some embodiments generally provide shunts composed of a material that has an elasticity modulus that is compatible with an elasticity modulus of tissue surrounding the shunt. In this manner, shunts of some embodiments are flexibility matched with the surrounding tissue, and thus will remain in place after implantation without the need for any type of anchor that interacts with the surrounding tissue. Consequently, shunts of some embodiments will maintain fluid flow away for an anterior chamber of the eye after implantation without causing irritation or inflammation to the tissue surrounding the eye.
• Elastic modulus, or modulus of elasticity, is a mathematical description of an object or substance's tendency to be deformed elastically when a force is applied to it. The elastic modulus of an object is defined as the slope of its stress-strain curve in the elastic deformation region:
• $\lambda \stackrel{\mathrm{def}}{=}\frac{\mathrm{Stress}}{\mathrm{Strain}}$
• where lambda (λ) is the elastic modulus; stress is the force causing the deformation divided by the area to which the force is applied; and strain is the ratio of the change caused by the stress to the original state of the object. The elasticity modulus may also be known as Young's modulus (E), which describes tensile elasticity, or the tendency of an object to deform along an axis when opposing forces are applied along that axis. Young's modulus is defined as the ratio of tensile stress to tensile strain. For further description regarding elasticity modulus and Young's modulus, see for example Gere (Mechanics of Materials, 6^thEdition, 2004, Thomson), the content of which is incorporated by reference herein in its entirety.
• The elasticity modulus of any tissue can be determined by one of skill in the art. See for example Samani et al. (Phys. Med. Biol. 48:2183, 2003); Erkamp et al. (Measuring The Elastic Modulus Of Small Tissue Samples, Biomedical Engineering Department and Electrical Engineering and Computer Science Department University of Michigan Ann Arbor, Mich. 48109-2125; and Institute of Mathematical Problems in Biology Russian Academy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen et al. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996); Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No. 96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol. 16:241-246, 1990), each of which provides methods of determining the elasticity modulus of body tissues. The content of each of these is incorporated by reference herein in its entirety.
• The elasticity modulus of tissues of different organs is known in the art. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007) and Friberg (Experimental Eye Research, 473:429-436, 1988) show the elasticity modulus of the cornea and the sclera of the eye. The content of each of these references is incorporated by reference herein in its entirety. Chen, Hall, and Parker show the elasticity modulus of different muscles and the liver. Erkamp shows the elasticity modulus of the kidney.
• Shunts of some embodiments are composed of a material that is compatible with an elasticity modulus of tissue surrounding the shunt. In certain embodiments, the material has an elasticity modulus that is substantially identical to the elasticity modulus of the tissue surrounding the shunt. In other embodiments, the material has an elasticity modulus that is greater than the elasticity modulus of the tissue surrounding the shunt. Exemplary materials includes biocompatible polymers, such as polycarbonate, polyethylene, polyethylene terephthalate, polyimide, polystyrene, polypropylene, poly(styrene-b-isobutylene-b-styrene), or silicone rubber.
• In some embodiments, shunts of some embodiments are composed of a material that has an elasticity modulus that is compatible with the elasticity modulus of tissue in the eye, particularly scleral tissue. In certain embodiments, compatible materials are those materials that are softer than scleral tissue or marginally harder than scleral tissue, yet soft enough to prohibit shunt migration. The elasticity modulus for anterior scleral tissue is approximately 2.9±1.4×10⁶N/m², and 1.8±1.1×10⁶N/m²for posterior scleral tissue. See Friberg (Experimental Eye Research, 473:429-436, 1988). An exemplary material is cross linked gelatin derived from Bovine or Porcine Collagen.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm.
Shunts Reactive to Pressure
• In other aspects, some embodiments generally provide shunts in which a portion of the shunt is composed of a flexible material that is reactive to pressure, i.e., the diameter of the flexible portion of the shunt fluctuates depending upon the pressures exerted on that portion of the shunt.FIG. 6 provides a schematic of ashunt23 having aflexible portion51. In this figure, theflexible portion51 is shown in the middle of theshunt23. However, theflexible portion51 may be located in any portion of the shunt, such as the proximal or distal portion of the shunt. In certain embodiments, the entire shunt is composed of the flexible material, and thus the entire shunt is flexible and reactive to pressure.
• Theflexible portion51 of theshunt23 acts as a valve that regulates fluid flow through the shunt. The human eye produces aqueous humor at a rate of about 2 μl/min for approximately 3 ml/day. The entire aqueous volume is about 0.25 ml. When the pressure in the anterior chamber falls after surgery to about 7-8 mmHg, it is assumed the majority of the aqueous humor is exiting the eye through the implant since venous backpressure prevents any significant outflow through normal drainage structures (e.g., the trabecular meshwork).
• After implantation, intraocular shunts have pressure exerted upon them by tissues surrounding the shunt (e.g., scleral tissue such as the sclera channel and the sclera exit) and pressure exerted upon them by aqueous humor flowing through the shunt. The flow through the shunt, and thus the pressure exerted by the fluid on the shunt, is calculated by the equation:
• $\Phi =\frac{\mathrm{dV}}{\mathrm{dT}}=v\pi {\mathrm{<figure-callout\; label="R"\; filenames="US20190021907A1-20190124-D00001.png"\; state="\{\{state\}\}">R</figure-callout>}}^2=\frac{\pi R^4}{8\eta }\left(\frac{-\Delta P}{\Delta x}\right)=\frac{\pi R^4}{8\eta }\frac{\Delta P}{L}$
• where Φ is the volumetric flow rate; V is a volume of the liquid poured (cubic meters); t is the time (seconds); v is mean fluid velocity along the length of the tube (meters/second); x is a distance in direction of flow (meters); R is the internal radius of the tube (meters); ΔP is the pressure difference between the two ends (pascals); η is the dynamic fluid viscosity (pascal-second (Pa·s)); and L is the total length of the tube in the x direction (meters).
• FIG. 7A provides a schematic of ashunt26 implanted into an eye for regulation of fluid flow from the anterior chamber of the eye to an area of lower pressure (e.g., the intrascleral space). The shunt is implanted such that aproximal end27 of theshunt26 resides in theanterior chamber28 of the eye, and adistal end29 of theshunt26 resides outside of the anterior chamber to conduct aqueous humor from the anterior chamber to an area of lower pressure. Aflexible portion30 of theshunt26 spans at least a portion of the sclera of the eye. As shown inFIG. 7A, the flexible portion spans an entire length of thesclera31.
• When the pressure exerted on theflexible portion30 of theshunt26 by sclera31 (vertical arrows) is greater than the pressure exerted on theflexible portion30 of theshunt26 by the fluid flowing through the shunt (horizontal arrow), theflexible portion30 decreases in diameter, restricting flow through the shunt26 (FIG. 7B). The restricted flow results in aqueous humor leaving theanterior chamber28 at a reduced rate.
• When the pressure exerted on theflexible portion30 of theshunt26 by the fluid flowing through the shunt (horizontal arrow) is greater than the pressure exerted on theflexible portion30 of theshunt26 by the sclera31 (vertical arrows), theflexible portion30 increases in diameter, increasing flow through the shunt26 (FIG. 7C). The increased flow results in aqueous humor leaving theanterior chamber28 at an increased rate.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm.
• In some embodiments, the shunt has a length of about 6 mm and an inner diameter of about 64 μm. With these dimensions, the pressure difference between the proximal end of the shunt that resides in the anterior chamber and the distal end of the shunt that resides outside the anterior chamber is about 4.3 mmHg. Such dimensions thus allow the implant to act as a controlled valve and protect the integrity of the anterior chamber.
• It will be appreciated that different dimensioned implants may be used. For example, shunts that range in length from about 2 mm to about 10 mm and have a range in inner diameter from about 10 μm to about 100 μm allow for pressure control from approximately 0.5 mmHg to approximately 20 mmHg.
• The material of the flexible portion and the thickness of the wall of the flexible portion will determine how reactive the flexible portion is to the pressures exerted upon it by the surrounding tissue and the fluid flowing through the shunt. Generally, with a certain material, the thicker the flexible portion, the less responsive the portion will be to pressure. In certain embodiments, the flexible portion is a gelatin or other similar material, and the thickness of the gelatin material forming the wall of the flexible portion ranges from about 10 μm thick to about 100 μm thick.
• In a certain embodiment, the gelatin used for making the flexible portion is known as gelatin Type B from bovine skin. An exemplary gelatin is PB Leiner gelatin from bovine skin, Type B, 225 Bloom, USP. Another material that may be used in the making of the flexible portion is a gelatin Type A from porcine skin, also available from Sigma Chemical. Such gelatin is available from Sigma Chemical Company of St. Louis, Mo. under Code G-9382. Still other suitable gelatins include bovine bone gelatin, porcine bone gelatin and human-derived gelatins. In addition to gelatins, the flexible portion may be made of hydroxypropyl methylcellulose (HPMC), collagen, polylactic acid, polylglycolic acid, hyaluronic acid and glycosaminoglycans.
• In certain embodiments, the gelatin is cross-linked. Cross-linking increases the inter- and intramolecular binding of the gelatin substrate. Any method for cross-linking the gelatin may be used. In some embodiments, the formed gelatin is treated with a solution of a cross-linking agent such as, but not limited to, glutaraldehyde. Other suitable compounds for cross-linking include 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Cross-linking by radiation, such as gamma or electron beam (e-beam) may be alternatively employed.
• In one embodiment, the gelatin is contacted with a solution of approximately 25% glutaraldehyde for a selected period of time. One suitable form of glutaraldehyde is a grade 1G5882 glutaraldehyde available from Sigma Aldridge Company of Germany, although other glutaraldehyde solutions may also be used. The pH of the glutaraldehyde solution should be in the range of 7 to 7.8 and, more particularly, 7.35-7.44 and typically approximately 7.4+/−0.01. If necessary, the pH may be adjusted by adding a suitable amount of a base such as sodium hydroxide as needed.
• Methods for forming the flexible portion of the shunt are shown for example in Yu et al. (U.S. Patent Pub. No. 2008/0108933), the content of which is incorporated by reference herein in its entirety. In an exemplary protocol, the flexible portion may be made by dipping a core or substrate such as a wire of a suitable diameter in a solution of gelatin. The gelatin solution is typically prepared by dissolving a gelatin powder in de-ionized water or sterile water for injection and placing the dissolved gelatin in a water bath at a temperature of approximately 55° C. with thorough mixing to ensure complete dissolution of the gelatin. In one embodiment, the ratio of solid gelatin to water is approximately 10% to 50% gelatin by weight to 50% to 90% by weight of water. In an embodiment, the gelatin solution includes approximately 40% by weight, gelatin dissolved in water. The resulting gelatin solution should be devoid of air bubbles and has a viscosity that is between approximately 200-500 cp and more particularly between approximately 260 and 410 cp (centipoise).
• Once the gelatin solution has been prepared, in accordance with the method described above, supporting structures such as wires having a selected diameter are dipped into the solution to form the flexible portion. Stainless steel wires coated with a biocompatible, lubricious material such as polytetrafluoroethylene (Teflon) are preferred.
• Typically, the wires are gently lowered into a container of the gelatin solution and then slowly withdrawn. The rate of movement is selected to control the thickness of the coat. In addition, it is preferred that the tube be removed at a constant rate in order to provide the desired coating. To ensure that the gelatin is spread evenly over the surface of the wire, in one embodiment, the wires may be rotated in a stream of cool air which helps to set the gelatin solution and affix film onto the wire. Dipping and withdrawing the wire supports may be repeated several times to further ensure even coating of the gelatin. Once the wires have been sufficiently coated with gelatin, the resulting gelatin films on the wire may be dried at room temperature for at least 1 hour, and more preferably, approximately 10 to 24 hours. Apparatus for forming gelatin tubes are described in Yu et al. (U.S. Patent Pub. No. 2008/0108933).
• Once dried, the formed flexible portions may be treated with a cross-linking agent. In one embodiment, the formed flexible portion may be cross-linked by dipping the wire (with film thereon) into the 25% glutaraldehyde solution, at pH of approximately 7.0-7.8 and more preferably approximately 7.35-7.44 at room temperature for at least 4 hours and preferably between approximately 10 to 36 hours, depending on the degree of cross-linking desired. In one embodiment, the formed flexible portion is contacted with a cross-linking agent such as gluteraldehyde for at least approximately 16 hours. Cross-linking can also be accelerated when it is performed a high temperature. It is believed that the degree of cross-linking is proportional to the bioabsorption time of the shunt once implanted. In general, the more cross-linking, the longer the survival of the shunt in the body.
• The residual glutaraldehyde or other cross-linking agent is removed from the formed flexible portion by soaking the tubes in a volume of sterile water for injection. The water may optionally be replaced at regular intervals, circulated or re-circulated to accelerate diffusion of the unbound glutaraldehyde from the tube. The tubes are washed for a period of a few hours to a period of a few months with the ideal time being 3-14 days. The now cross-linked gelatin tubes may then be dried (cured) at ambient temperature for a selected period of time. It has been observed that a drying period of approximately 48-96 hours and more typically 3 days (i.e., 72 hours) may be preferred for the formation of the cross-linked gelatin tubes.
• Where a cross-linking agent is used, it may be desirable to include a quenching agent in the method of making the flexible portion. Quenching agents remove unbound molecules of the cross-linking agent from the formed flexible portion. In certain cases, removing the cross-linking agent may reduce the potential toxicity to a patient if too much of the cross-linking agent is released from the flexible portion. In certain embodiments, the formed flexible portion is contacted with the quenching agent after the cross-linking treatment and, may be included with the washing/rinsing solution. Examples of quenching agents include glycine or sodium borohydride.
• After the requisite drying period, the formed and cross-linked flexible portion is removed from the underlying supports or wires. In one embodiment, wire tubes may be cut at two ends and the formed gelatin flexible portion slowly removed from the wire support. In another embodiment, wires with gelatin film thereon, may be pushed off using a plunger or tube to remove the formed gelatin flexible portion.
Multi-Port Shunts
• Other aspects of some embodiments generally provide multi-port shunts. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt even if one or more ports of the shunt become clogged with particulate. In certain embodiments, the shunt includes a hollow body defining a flow path and more than two ports, in which the body is configured such that a proximal portion receives fluid from the anterior chamber of an eye and a distal portion directs the fluid to drainage structures associated with the intrascleral space.
• The shunt may have many different configurations.FIGS. 8A-8C shows an embodiment of ashunt32 in which the proximal portion of the shunt (i.e., the portion disposed within the anterior chamber of the eye) includes more than one port (designated asnumbers33a-33e) and the distal portion of the shunt (i.e., the portion that is located in the intrascleral space) includes asingle port34.FIG. 8B shows another embodiment of ashunt32 in which the proximal portion includes asingle port33 and the distal portion includes more than one port (designated asnumbers34a-34e).FIG. 8C shows another embodiment of ashunt32 in which the proximal portions include more than one port (designated asnumbers33a-33e) and the distal portions include more than one port (designated asnumbers34a-34e). WhileFIGS. 8A-8C show shunts have five ports at the proximal portion, distal portion, or both, those shunts are only exemplary embodiments. The ports may be located along any portion of the shunt, and shunts of some embodiments include all shunts having more than two ports. For example, shunts of some embodiments may include at least three ports, at least four ports, at least five ports, at least 10 ports, at least 15 ports, or at least 20 ports.
• The ports may be positioned in various different orientations and along various different portions of the shunt. In certain embodiments, at least one of the ports is oriented at an angle to the length of the body. In certain embodiments, at least one of the ports is oriented 90° to the length of the body. See for exampleFIG. 8A, which depictsports33a,33b,33d, and33eas being oriented at a 90° angle to port33c.
• The ports may have the same or different inner diameters. In certain embodiments, at least one of the ports has an inner diameter that is different from the inner diameters of the other ports.FIGS. 9A and 9B show an embodiment of ashunt32 having multiple ports (33aand33b) at a proximal end and asingle port34 at a distal end.FIG. 9A shows thatport33bhas an inner diameter that is different from the inner diameters ofports33aand34. In this figure, the inner diameter ofport33bis less than the inner diameter ofports33aand34. An exemplary inner diameter ofport33bis from about 20 μm to about 40 μm, particularly about 30 μm. In other embodiments, the inner diameter ofport33bis greater than the inner diameter ofports33aand34. See for exampleFIG. 9B.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm. Shunts of some embodiments may be made from any biocompatible material. An exemplary material is gelatin. Methods of making shunts composed of gelatin are described above.
• Shunts with Overflow Ports
• Other aspects of some embodiments generally provide shunts with overflow ports. Those shunts are configured such that the overflow port remains partially or completely closed until there is a pressure build-up within the shunt sufficient to force open the overflow port. Such pressure build-up typically results from particulate partially or fully clogging an entry or an exit port of the shunt. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt by the overflow port even if one port of the shunt becomes clogged with particulate.
• In certain embodiments, the shunt includes a hollow body defining an inlet configured to receive fluid from an anterior chamber of an eye and an outlet configured to direct the fluid to the intrascleral space, the body further including at least one slit. The slit may be located at any place along the body of the shunt.FIG. 10A shows ashunt35 having aninlet36, anoutlet37, and aslit38 located in proximity to theinlet36.FIG. 10B shows ashunt35 having aninlet36, anoutlet37, and aslit39 located in proximity to theoutlet37.FIG. 10C shows ashunt35 having aninlet36, anoutlet37, aslit38 located in proximity to theinlet36, and aslit39 located in proximity to theoutlet37.
• WhileFIGS. 10A-10C show shunts have only a single overflow port at the proximal portion, the distal portion, or both the proximal and distal portions, those shunts are only exemplary embodiments. The overflow port(s) may be located along any portion of the shunt, and shunts of some embodiments include shunts having more than one overflow port. In certain embodiments, shunts of some embodiments include more than one overflow port at the proximal portion, the distal portion, or both. For example,FIG. 11 shows ashunt40 having aninlet41, anoutlet42, and slits43aand43blocated in proximity to theinlet41. Shunts of some embodiments may include at least two overflow ports, at least three overflow ports, at least four overflow ports, at least five overflow ports, at least 10 overflow ports, at least 15 overflow ports, or at least 20 overflow ports. In certain embodiments, shunts of some embodiments include two slits that overlap and are oriented at 90° to each other, thereby forming a cross.
• In certain embodiments, the slit may be at the proximal or the distal end of the shunt, producing a split in the proximal or the distal end of the implant.FIG. 12 shows an embodiment of ashunt44 having aninlet45,outlet46, and aslit47 that is located at the proximal end of the shunt, producing a split in theinlet45 of the shunt.
• In certain embodiments, the slit has a width that is substantially the same or less than an inner diameter of the inlet. In other embodiments, the slit has a width that is substantially the same or less than an inner diameter of the outlet. In certain embodiments, the slit has a length that ranges from about 0.05 mm to about 2 mm, and a width that ranges from about 10 μm to about 200 μm. Generally, the slit does not direct the fluid unless the outlet is obstructed. However, the shunt may be configured such that the slit does direct at least some of the fluid even if the inlet or outlet is not obstructed.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm. Shunts of some embodiments may be made from any biocompatible material. An exemplary material is gelatin. Methods of making shunts composed of gelatin are described above.
Shunts Having a Variable Inner Diameter
• In other aspects, some embodiments generally provide a shunt having a variable inner diameter. In some embodiments, the diameter increases from inlet to outlet of the shunt. By having a variable inner diameter that increases from inlet to outlet, a pressure gradient is produced and particulate that may otherwise clog the inlet of the shunt is forced through the inlet due to the pressure gradient. Further, the particulate will flow out of the shunt because the diameter only increases after the inlet.
• FIG. 13 shows an embodiment of ashunt48 having aninlet49 configured to receive fluid from an anterior chamber of an eye and anoutlet50 configured to direct the fluid to a location of lower pressure with respect to the anterior chamber, in which the body further includes a variable inner diameter that increases along the length of the body from theinlet49 to theoutlet50. In certain embodiments, the inner diameter continuously increases along the length of the body, for example as shown inFIG. 13. In other embodiments, the inner diameter remains constant along portions of the length of the body.
• In exemplary embodiments, the inner diameter may range in size from about 10 μm to about 200 μm, and the inner diameter at the outlet may range in size from about 15 μm to about 300 μm. Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm. Shunts of some embodiments may be made from any biocompatible material. An exemplary material is gelatin. Methods of making shunts composed of gelatin are described above.
Shunts Having Pronged Ends
• In other aspects, some embodiments generally provide shunts for facilitating conduction of fluid flow away from an organ, the shunt including a body, in which at least one end of the shunt is shaped to have a plurality of prongs. Such shunts reduce probability of the shunt clogging after implantation because fluid can enter or exit the shunt by any space between the prongs even if one portion of the shunt becomes clogged with particulate.
• FIGS. 14A-14D show embodiments of ashunt52 in which at least one end of theshunt52 includes a plurality of prongs53a-d.FIGS. 14A-14D show embodiments in which both a proximal end and a distal end of the shunt are shaped to have the plurality of prongs. However, numerous different configurations are envisioned. For example, in certain embodiments, only the proximal end of the shunt is shaped to have the plurality of prongs. In other embodiments, only the distal end of the shunt is shaped to have the plurality of prongs.
• Prongs53a-dcan have any shape (i.e., width, length, height).FIGS. 14A and 14B show prongs53a-das straight prongs. In this embodiment, the spacing between the prongs53a-dis the same. In another embodiment shown inFIGS. 14C and 14D, prongs53a-dare tapered. In this embodiment, the spacing between the prongs increases toward a proximal and/or distal end of theshunt52.
• FIGS. 14A-14D show embodiments that include four prongs. However, shunts of some embodiments may accommodate any number of prongs, such as two prongs, three prongs, four prongs, five prongs, six prongs, seven prongs, eight prongs, nine prongs, ten prongs, etc. The number of prongs chosen will depend on the desired flow characteristics of the shunt.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm. Shunts of some embodiments may be made from any biocompatible material. An exemplary material is gelatin. Methods of making shunts composed of gelatin are described above.
Shunts Having a Longitudinal Slit
• In other aspects, some embodiments generally provide a shunt for draining fluid from an anterior chamber of an eye that includes a hollow body defining an inlet configured to receive fluid from an anterior chamber of the eye and an outlet configured to direct the fluid to a location of lower pressure with respect to the anterior chamber; the shunt being configured such that at least one end of the shunt includes a longitudinal slit. Such shunts reduce probability of the shunt clogging after implantation because the end(s) of the shunt can more easily pass particulate which would generally clog a shunt lacking the slits.
• FIGS. 15A-15D show embodiments of ashunt54 in which at least one end of theshunt54 includes alongitudinal slit55 that produces atop portion56aand abottom portion56bin a proximal and/or distal end of theshunt54.FIGS. 15A-15D show an embodiment in which both a proximal end and a distal end include alongitudinal slit55 that produces atop portion56aand abottom portion56bin both ends of theshunt54. However, numerous different configurations are envisioned. For example, in certain embodiments, only the proximal end of the shunt includeslongitudinal slit55. In other embodiments, only the distal end of the shunt includeslongitudinal slit55.
• Longitudinal slit55 can have any shape (i.e., width, length, height).FIGS. 15A and 15B show alongitudinal slit55 that is straight such that the space between thetop portion56aand thebottom portion56bremains the same along the length of theslit55. In another embodiment shown inFIGS. 15C-15D,longitudinal slit55 is tapered. In this embodiment, the space between the top portion45aand thebottom portion56bincreases toward a proximal and/or distal end of theshunt54.
• Some embodiments encompass shunts of different shapes and different dimensions, and the shunts of some embodiments may be any shape or any dimension that may be accommodated by the eye. In certain embodiments, the intraocular shunt is of a cylindrical shape and has an outside cylindrical wall and a hollow interior. The shunt may have an inside diameter from approximately 10 μm to approximately 250 μm, an outside diameter from approximately 100 μm to approximately 450 μm, and a length from approximately 2 mm to approximately 10 mm. Shunts of some embodiments may be made from any biocompatible material. An exemplary material is gelatin. Methods of making shunts composed of gelatin are described above.
Pharmaceutical Agents
• In certain embodiments, shunts of some embodiments may be coated or impregnated with at least one pharmaceutical and/or biological agent or a combination thereof. The pharmaceutical and/or biological agent may coat or impregnate an entire exterior of the shunt, an entire interior of the shunt, or both. Alternatively, the pharmaceutical or biological agent may coat and/or impregnate a portion of an exterior of the shunt, a portion of an interior of the shunt, or both. Methods of coating and/or impregnating an intraocular shunt with a pharmaceutical and/or biological agent are known in the art. See for example, Darouiche (U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283; 5,853,745; and 5,624,704) and Yu et al. (U.S. Patent Pub. No. 2008/0108933). The content of each of these references is incorporated by reference herein its entirety.
• In certain embodiments, the exterior portion of the shunt that resides in the anterior chamber after implantation (e.g., about 1 mm of the proximal end of the shunt) is coated and/or impregnated with the pharmaceutical or biological agent. In other embodiments, the exterior of the shunt that resides in the scleral tissue after implantation of the shunt is coated and/or impregnated with the pharmaceutical or biological agent. In other embodiments, the exterior portion of the shunt that resides in the intrascleral space after implantation is coated and/or impregnated with the pharmaceutical or biological agent. In embodiments in which the pharmaceutical or biological agent coats and/or impregnates the interior of the shunt, the agent may be flushed through the shunt and into the area of lower pressure (e.g., the intrascleral space).
• Any pharmaceutical and/or biological agent or combination thereof may be used with shunts of some embodiments. The pharmaceutical and/or biological agent may be released over a short period of time (e.g., seconds) or may be released over longer periods of time (e.g., days, weeks, months, or even years). Exemplary agents include anti-mitotic pharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen, Avastin, VEGF or steroids).
Deployment Devices
• Deployment into the eye of an intraocular shunt according to some embodiments can be achieved using a hollow shaft configured to hold the shunt, as described herein. The hollow shaft can be coupled to a deployment device or part of the deployment device itself. Deployment devices that are suitable for deploying shunts according to some embodiments include but are not limited to the deployment devices described in U.S. Pat. No. 6,007,511, U.S. Pat. No. 6,544,249, and U.S. Publication No. 2008/0108933, the contents of which are each incorporated herein by reference in their entireties. In other embodiments, the deployment devices are devices as described in co-pending and co-owned U.S. patent application Ser. No. 12/946,222 filed on Nov. 15, 2010, or deployment devices described in co-pending and co-owned U.S. patent application Ser. No. 12/946,645, filed on Nov. 15, 2010, the entire content of each of which is incorporated by reference herein.
• A shunt deployment device, such as those disclosed herein, can be used to implant the shunt in accordance with a variety of potential procedures, which can be modified or updated, according to aspects of the disclosure herein, as well as future methodologies and device features. For example, as discussed and shown below with regard toFIGS. 52A-54E of copending U.S. patent application Ser. No. 14/317,676, filed on Jun. 27, 2014, the entirety of which is incorporated herein by reference, a shunt deployment device can be used to implant a shunt using a variety of different procedures. The deployment device can be manual or automatic and can include features of one or more of the devices discussed or mentioned herein.
• In still other embodiments, the shunts according to some embodiments are deployed into the eye using thedeployment device100 depicted inFIG. 16. WhileFIG. 16 shows a handheld manually operated shunt deployment device, it will be appreciated that devices of some embodiments may be coupled with robotic systems and may be completely or partially automated. As shown inFIG. 16,deployment device100 includes a generally cylindrical body orhousing101, however, the body shape ofhousing101 could be other than cylindrical.Housing101 may have an ergonomical shape, allowing for comfortable grasping by an operator.Housing101 is shown withoptional grooves102 to allow for easier gripping by a surgeon.
• According to some embodiments, the shunt can be advanced into the eye tissue at a rate of between about 0.15 mm/sec to about 0.85 mm/sec. Further, in some embodiments, the shunt can be advanced into the eye tissue at a rate of between about 0.25 mm/sec to about 0.65 mm/sec.
• Housing101 is shown having a larger proximal portion that tapers to a distal portion. The distal portion includes ahollow sleeve105. Thehollow sleeve105 is configured for insertion into an eye and to extend into an anterior chamber of an eye. The hollow sleeve is visible within an anterior chamber of an eye. According to some embodiment, thesleeve105 can provide a visual preview or guide for an operator as to placement of the proximal portion of the shunt within the anterior chamber of an eye, as discussed below with regard toFIGS. 52A-52E of copending U.S. patent application Ser. No. 14/317,676, filed on Jun. 27, 2014. Thesleeve105 can provide a visual reference point that may be used by an operator to holddevice100 steady during the shunt deployment process, thereby assuring optimal longitudinal placement of the shunt within the eye. Thesleeve105 may include an edge at a distal end that provides resistance feedback to an operator upon insertion of thedeployment device100 within an eye of a person. Upon advancement of thedevice100 across an anterior chamber of the eye, thehollow sleeve105 will eventually contact the sclera, providing resistance feedback to an operator that no further advancement of thedevice100 is necessary. The edge of thesleeve105, prevents theshaft104 from accidentally being pushed too far through the sclera. Atemporary guard108 is configured to fit aroundsleeve105 and extend beyond an end ofsleeve105. The guard is used during shipping of the device and protects an operator from a distal end of ahollow shaft104 that extends beyond the end of thesleeve105. The guard is removed prior to use of the device.
• Housing101 is open at its proximal end, such that a portion of adeployment mechanism103 may extend from the proximal end of thehousing101. A distal end ofhousing101 is also open such that at least a portion of ahollow shaft104 may extend through and beyond the distal end of thehousing101.Housing101 further includes aslot106 through which an operator, such as a surgeon, using thedevice100 may view anindicator107 on thedeployment mechanism103.
• Housing101 may be made of any material that is suitable for use in medical devices. For example,housing101 may be made of a lightweight aluminum or a biocompatible plastic material. Examples of such suitable plastic materials include polycarbonate and other polymeric resins such as DELRIN and ULTEM. In certain embodiments,housing101 is made of a material that may be autoclaved, and thus allow forhousing101 to be re-usable. Alternatively,device100, may be sold as a one-time-use device, and thus the material of the housing does not need to be a material that is autoclavable.
• Housing101 may be made of multiple components that connect together to form the housing.FIG. 17 shows an exploded view ofdeployment device100. In this figure,housing101, is shown having threecomponents101a,101b, and101c. The components are designed to screw together to formhousing101.FIGS. 18A-18D also showdeployment mechanism103. Thehousing101 is designed such thatdeployment mechanism103 fits within assembledhousing101.Housing101 is designed such that components ofdeployment mechanism103 are movable withinhousing101.
• FIGS. 18A-18D show different enlarged views of thedeployment mechanism103.Deployment mechanism103 may be made of any material that is suitable for use in medical devices. For example,deployment mechanism103 may be made of a lightweight aluminum or a biocompatible plastic material. Examples of such suitable plastic materials include polycarbonate and other polymeric resins such as DELRIN and ULTEM. In certain embodiments,deployment mechanism103 is made of a material that may be autoclaved, and thus allow fordeployment mechanism103 to be re-usable. Alternatively,device100 may be sold as a one-time-use device, and thus the material of the deployment mechanism does not need to be a material that is autoclavable.
• Deployment mechanism103 includes adistal portion109 and aproximal portion110. Thedeployment mechanism103 is configured such thatdistal portion109 is movable withinproximal portion110. More particularly,distal portion109 is capable of partially retracting to withinproximal portion110.
• In this embodiment, thedistal portion109 is shown to taper to a connection with ahollow shaft104. This embodiment is illustrated such that the connection between thehollow shaft104 and thedistal portion109 of thedeployment mechanism103 occurs inside thehousing101. In other embodiments, the connection betweenhollow shaft104 and theproximal portion109 of thedeployment mechanism103 may occur outside of thehousing101.Hollow shaft104 may be removable from thedistal portion109 of thedeployment mechanism103. Alternatively, thehollow shaft104 may be permanently coupled to thedistal portion109 of thedeployment mechanism103.
• Generally,hollow shaft104 is configured to hold an intraocular shunt, such as the intraocular shunts according to some embodiments. Theshaft104 may be any length. A usable length of the shaft may be anywhere from about 5 mm to about 40 mm, and is 15 mm in certain embodiments. In certain embodiments, the shaft is straight. In other embodiments, shaft is of a shape other than straight, for example a shaft having a bend along its length.
• A proximal portion of the deployment mechanism includesoptional grooves116 to allow for easier gripping by an operator for easier rotation of the deployment mechanism, which will be discussed in more detail below. Theproximal portion110 of the deployment mechanism also includes at least one indicator that provides feedback to an operator as to the state of the deployment mechanism. The indicator may be any type of indicator known in the art, for example a visual indicator, an audio indicator, or a tactile indicator.FIGS. 18A-18D shows a deployment mechanism having two indicators, aready indicator111 and a deployedindicator119.Ready indicator111 provides feedback to an operator that the deployment mechanism is in a configuration for deployment of an intraocular shunt from thedeployment device100. Theready indicator111 is shown in this embodiment as a green oval having a triangle within the oval. Deployedindicator119 provides feedback to the operator that the deployment mechanism has been fully engaged and has deployed the shunt from thedeployment device100. The deployedindicator119 is shown in this embodiment as a yellow oval having a black square within the oval. The indicators are located on the deployment mechanism such that when assembled, theindicators111 and119 may be seen throughslot106 inhousing101.
• Theproximal portion110 includes astationary portion110band arotating portion110a. Theproximal portion110 includes achannel112 that runs part of the length ofstationary portion110band the entire length of rotatingportion110a. Thechannel112 is configured to interact with aprotrusion117 on an interior portion ofhousing component101a(FIGS. 19A and 19B). During assembly, theprotrusion117 onhousing component101ais aligned withchannel112 on thestationary portion110bandrotating portion110aof thedeployment mechanism103. Theproximal portion110 ofdeployment mechanism103 is slid withinhousing component101auntil theprotrusion117 sits withinstationary portion110b(FIG. 19C). Assembled, theprotrusion117 interacts with thestationary portion110bof thedeployment mechanism103 and prevents rotation ofstationary portion110b. In this configuration, rotatingportion110ais free to rotate withinhousing component101a.
• Referring back toFIGS. 18A-18D, the rotatingportion110aofproximal portion110 ofdeployment mechanism103 also includeschannels113a,113b, and113c.Channel113aincludes afirst portion113a1 that is straight and runs perpendicular to the length of therotating portion110a, and asecond portion113a2 that runs diagonally along the length of rotatingportion110a, downwardly toward a proximal end of thedeployment mechanism103.Channel113bincludes afirst portion113b1 that runs diagonally along the length of therotating portion110a, downwardly toward a distal end of thedeployment mechanism103, and a second portion that is straight and runs perpendicular to the length of therotating portion110a. The point at whichfirst portion113a1 transitions tosecond portion113a2 alongchannel113a, is the same as the point at whichfirst portion113b1 transitions tosecond portion113b2 alongchannel113b.Channel113cis straight and runs perpendicular to the length of therotating portion110a. Within each ofchannels113a,113b, and113c, sitmembers114a,114b, and114crespectively.Members114a,114b, and114care movable withinchannels113a,113b, and113c.Members114a,114b, and114calso act as stoppers that limit movement of rotatingportion110a, which thereby limits axial movement of theshaft104.
• FIG. 20 shows a cross-sectional view ofdeployment mechanism103.Member114ais connected to thedistal portion109 of thedeployment mechanism103. Movement ofmember114aresults in retraction of thedistal portion109 of thedeployment mechanism103 to within theproximal portion110 of thedeployment mechanism103.Member114bis connected to apusher component118. Thepusher component118 extends through thedistal portion109 of thedeployment mechanism103 and extends into a portion ofhollow shaft104. The pusher component is involved in deployment of a shunt from thehollow shaft104. An exemplary pusher component is a plunger. Movement ofmember114bengagespusher118 and results inpusher118 advancing withinhollow shaft104.
• Reference is now made toFIGS. 21A-23D, which accompany the following discussion regarding deployment of ashunt115 fromdeployment device100.FIG. 21A showsdeployment device100 in a pre-deployment configuration. In this configuration,shunt115 is loaded within hollow shaft104 (FIG. 21C). As shown inFIG. 21C,shunt115 is only partially withinshaft104, such that a portion of the shunt is exposed. However, theshunt115 does not extend beyond the end of theshaft104. In other embodiments, theshunt115 is completely disposed withinhollow shaft104. Theshunt115 is loaded intohollow shaft104 such that the shunt abutspusher component118 withinhollow shaft104. A distal end ofshaft104 is beveled to assist in piercing tissue of the eye.
• Additionally, in the pre-deployment configuration, a portion of theshaft104 extends beyond the sleeve105 (FIG. 21C). The deployment mechanism is configured such thatmember114aabuts a distal end of thefirst portion113a1 ofchannel113a, andmember114babut a proximal end of thefirst portion113b1 ofchannel113b(FIG. 21B). In this configuration, theready indicator111 is visible throughslot106 of thehousing101, providing feedback to an operator that the deployment mechanism is in a configuration for deployment of an intraocular shunt from the deployment device100 (FIG. 21A). In this configuration, thedevice100 is ready for insertion into an eye (insertion configuration or pre-deployment configuration). Methods for inserting and implanting shunts are discussed in further detail below.
• Once the device has been inserted into the eye and advanced to a location to where the shunt will be deployed, theshunt115 may be deployed from thedevice100. Thedeployment mechanism103 is a two-stage system. The first stage is engagement of thepusher component118 and the second stage is retraction of thedistal portion109 to within theproximal portion110 of thedeployment mechanism103. Rotation of therotating portion110aof theproximal portion110 of thedeployment mechanism103 sequentially engages the pusher component and then the retraction component.
• In the first stage of shunt deployment, the pusher component is engaged and the pusher partially deploys the shunt from the deployment device. During the first stage, rotatingportion110aof theproximal portion110 of thedeployment mechanism103 is rotated, resulting in movement ofmembers114aand114balongfirst portions113a1 and113b1 in channels raand113b. Since thefirst portion113a1 ofchannel113ais straight and runs perpendicular to the length of therotating portion110a, rotation of rotatingportion110adoes not cause axial movement ofmember114a. Without axial movement ofmember114a, there is no retraction of thedistal portion109 to within theproximal portion110 of thedeployment mechanism103. Since thefirst portion113b1 ofchannel113bruns diagonally along the length of therotating portion110a, upwardly toward a distal end of thedeployment mechanism103, rotation of rotatingportion110acauses axial movement ofmember114btoward a distal end of the device. Axial movement ofmember114btoward a distal end of the device results in forward advancement of thepusher component118 within thehollow shaft104. Such movement ofpusher component118 results in partially deployment of theshunt115 from theshaft104.
• FIGS. 22A-22C show schematics of the deployment mechanism at the end of the first stage of deployment of the shunt from the deployment device. As is shownFIG. 22A,members114aand114bhave finished traversing alongfirst portions113a1 and113b1 ofchannels113aand113b. Additionally,pusher component118 has advanced within hollow shaft104 (FIG. 22B), and shunt115 has been partially deployed from the hollow shaft104 (FIG. 22C). As is shown in these figures, a portion of theshunt115 extends beyond an end of theshaft104.
• In the second stage of shunt deployment, the retraction component is engaged and the distal portion of the deployment mechanism is retracted to within the proximal portion of the deployment mechanism, thereby completing deployment of the shunt from the deployment device. During the second stage, rotatingportion110aof theproximal portion110 of thedeployment mechanism103 is further rotated, resulting in movement ofmembers114aand114balongsecond portions113a2 and113b2 inchannels113aand113b. Since thesecond portion113b2 ofchannel113bis straight and runs perpendicular to the length of therotating portion110a, rotation of rotatingportion110adoes not cause axial movement ofmember114b. Without axial movement ofmember114b, there is no further advancement ofpusher118. Since thesecond portion113a2 ofchannel113aruns diagonally along the length of therotating portion110a, downwardly toward a proximal end of thedeployment mechanism103, rotation of rotatingportion110acauses axial movement ofmember114atoward a proximal end of the device. Axial movement ofmember114atoward a proximal end of the device results in retraction of thedistal portion109 to within theproximal portion110 of thedeployment mechanism103. Retraction of thedistal portion109, results in retraction of thehollow shaft104. Since theshunt115 abuts thepusher component118, the shunt remains stationary as thehollow shaft104 retracts from around the shunt115 (FIG. 22C). Theshaft104 retracts almost completely to within thesleeve105. During both stages of the deployment process, thesleeve105 remains stationary and in a fixed position.
• FIGS. 23A-23D show schematics of thedevice100 after deployment of theshunt115 from thedevice100.FIG. 23B shows a schematic of the deployment mechanism at the end of the second stage of deployment of the shunt from the deployment device. As is shown inFIG. 23B,members114aand114bhave finished traversing alongsecond portions113a2 and113b2 ofchannels113aand113b. Additionally,distal portion109 has retracted to withinproximal portion110, thus resulting in retraction of thehollow shaft104 to within thesleeve105.FIG. 23D shows an enlarged view of the distal portion of the deployment device after deployment of the shunt. This figure shows that thehollow shaft104 is not fully retracted to within thesleeve105 of thedeployment device100. However, in certain embodiments, theshaft104 may completely retract to within thesleeve105.
Additional Methods for Intrascleral Shunt Placement
• Some embodiments of the methods disclosed herein can involve creating an opening in the sclera (e.g., by piercing the sclera with a delivery device), and positioning a shunt in the anterior chamber of the eye such that the shunt terminates adjacent an opening formed in the sclera. In some embodiments, such placement can permit flow through the shunt to reach the intrascleral space, thereby facilitating fluid flow through both the opening and the intrascleral space. The outlet of the shunt may be positioned in different places within the intrascleral space. For example, the outlet of the shunt may be positioned within the sclera (e.g., within deep and superficial layers or tissue of the sclera). Alternatively, the outlet of the shunt may be positioned such that the outlet is even with or superficial to the opening through the sclera.
• Methods of implanting intraocular shunts are known in the art. Shunts may be implanted using an ab externo approach (entering through the conjunctiva and inwards through the sclera) or an ab interno approach (entering through the cornea, across the anterior chamber, through the trabecular meshwork and sclera). The deployment device may be any device that is suitable for implanting an intraocular shunt into an eye. Such devices generally include a shaft connected to a deployment mechanism. In some devices, a shunt is positioned over an exterior of the shaft and the deployment mechanism works to deploy the shunt from an exterior of the shaft. In other devices, the shaft is hollow and the shunt is at least partially disposed in the shaft. In those devices, the deployment mechanism works to deploy the shunt from within the shaft. Depending on the device, a distal portion of the shaft may be sharpened or blunt, or straight or curved.
Ab-Interno Approach
• Ab interno approaches for implanting an intraocular shunt in the subconjunctival space are shown for example in Yu et al. (U.S. Pat. No. 6,544,249 and U.S. Patent Publication No. 2008/0108933) and Prywes (U.S. Pat. No. 6,007,511), the contents of each of which are incorporated by reference herein in its entirety. An exemplary ab-interno method employs a transpupil approach and involves creating a first opening in the sclera of an eye, advancing a shaft configured to hold an intraocular shunt across an anterior chamber of an eye and through the sclera to create a second opening in the sclera, retracting the shaft through the second opening to within the sclera (i.e., the intrascleral space), deploying the shunt from the shaft such that the shunt forms a passage from the anterior chamber of the eye to the intrascleral space of the eye, such that an outlet of the shunt is positioned so that at least some of the fluid that exits the shunt flows through the second opening in the sclera, and withdrawing the shaft from the eye. The first opening in the sclera may be made in any manner. In certain embodiments, the shaft creates the first opening in the sclera. In other embodiments, a tool other than the shaft creates the first opening in the sclera.
• In certain embodiments, some embodiments of the methods disclosed herein can generally involve inserting into the eye a hollow shaft configured to hold an intraocular shunt. In certain embodiments, the hollow shaft is a component of a deployment device that may deploy the intraocular shunt. The shunt is then deployed from the shaft into the eye such that the shunt forms a passage from the anterior chamber into the sclera (i.e., the intrascleral space). The hollow shaft is then withdrawn from the eye.
• To place the shunt within the eye, a surgical intervention to implant the shunt is performed that involves inserting into the eye a deployment device that holds an intraocular shunt, and deploying at least a portion of the shunt within intrascleral space.FIGS. 24-31 provide an exemplary sequence for ab interno shunt placement. In certain embodiments, ahollow shaft209 of a deployment device holding theshunt212 enters the eye through the cornea (ab interno approach,FIG. 24). Theshaft209 is advanced across theanterior chamber210 in what is referred to as a transpupil implant insertion. Theshaft209 is advanced through the anterior angle tissues of the eye and into thesclera8 and further advanced until it passes through thesclera8, thereby forming a second opening in the sclera8 (FIGS. 25-26). Once the second opening in thesclera8 is achieved, theshaft209 is retracted all the way back through thesclera8 and into theanterior chamber210 of the eye (FIGS. 27-30). During this shaft retraction, theshunt212 is held in place by aplunger rod211 that is positioned behind the proximal end of theshunt212. After theshaft209 has been completely withdrawn from thesclera8, theplunger rod211 is withdrawn as well and the shunt implantation sequence is complete (FIG. 31). This process results in an implantedshunt212 in which a distal end of theshunt212 is proximate apassageway214 through thesclera8. Once fully deployed, a proximal end ofshunt212 resides in theanterior chamber210 and a distal end ofshunt212 resides in the intrascleral space. Preferably asleeve213 is used around theshaft212 and designed in length such that thesleeve213 acts as a stopper for the scleral penetration of the shaft and also determines the longitudinal placement of the proximal end of the shunt.
• Insertion of the shaft of the deployment device into thesclera8 produces a long scleral channel of about 2 mm to about 5 mm in length. Withdrawal of the shaft of the deployment device prior to deployment of theshunt212 from the device produces a space in which theshunt212 may be deployed. Deployment of theshunt212 allows foraqueous humor3 to drain into traditional fluid drainage channels of the eye (e.g., the intrascleral vein, the collector channel, Schlemm's canal, the trabecular outflow, and the uveoscleral outflow to the ciliary muscle. The deployment is performed such that an outlet of the shunt is positioned proximate the opening in the sclera so that at least some of the fluid that exits the shunt flows through the opening in the sclera, thereby ensuring that the intrascleral space does not become overwhelmed with fluid output from the shunt.
• Preferably, some embodiments of the methods disclosed herein are conducted by making an incision in the eye prior to insertion of the deployment device. In some embodiments of the methods disclosed herein may be conducted without making an incision in the eye prior to insertion of the deployment device. In certain embodiments, the shaft that is connected to the deployment device has a sharpened point or tip. In certain embodiments, the hollow shaft is a needle. Exemplary needles that may be used are commercially available from Terumo Medical Corp. (Elkington Md.). In some embodiments, the needle has a hollow interior and a beveled tip, and the intraocular shunt is held within the hollow interior of the needle. In another embodiment, the needle has a hollow interior and a triple ground point or tip.
• Some embodiments of the methods disclosed herein are preferably conducted without needing to remove an anatomical portion or feature of the eye, including but not limited to the trabecular meshwork, the iris, the cornea, or aqueous humor. Some embodiments of the methods disclosed herein are also preferably conducted without inducing substantial ocular inflammation, such as subconjunctival blebbing or endophthalmitis. Such methods can be achieved using an ab interno approach by inserting the hollow shaft configured to hold the intraocular shunt through the cornea, across the anterior chamber, through the trabecular meshwork and into the sclera. However, some embodiments of the methods disclosed herein may be conducted using an ab externo approach.
• When some embodiments of the methods disclosed herein are conducted using an ab interno approach, the angle of entry through the cornea as well as the up and downward forces applied to the shaft during the scleral penetration affect optimal placement of the shunt in the intrascleral space. Preferably, the hollow shaft is inserted into the eye at an angle superficial to the corneal limbus, in contrast with entering through or deep to the corneal limbus. For example, the hollow shaft is inserted about 0.25 mm to about 3.0 mm, preferably about 0.5 mm to about 2.5 mm, more preferably about 1.0 mm to about 2.0 mm superficial to the corneal limbus, or any specific value within said ranges, e.g., about 1.0 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2.0 mm superficial to the corneal limbus.
• Without intending to be bound by any theory, placement of the shunt farther from the limbus at the exit site, as provided by an angle of entry superficial to the limbus, as well as an S-shaped scleral tunnel (FIG. 32) due to applied up or downward pressure during the scleral penetration of the shaft is believed to provide access to more lymphatic channels for drainage of aqueous humor, such as the episcleral lymphatic network, in addition to the conjunctival lymphatic system.
Ab Externo Approach
• In other embodiments, an ab externo approach is employed. Ab externo implantation approaches are shown for example in Nissan et al. (U.S. Pat. No. 8,109,896), Tu et al. (U.S. Pat. No. 8,075,511), and Haffner et al. (U.S. Pat. No. 7,879,001), the content of each of which is incorporated by reference herein in its entirety. An exemplary ab externo approach avoids having to make a scleral flap. In this preferred embodiment, a distal end of the deployment device is used to make an opening into the eye and into the sclera. For example, a needle is inserted from ab externo through the sclera and exits the anterior angle of the eye. The needle is then withdrawn, leaving a scleral slit behind. A silicone tube with sufficient stiffness is then manually pushed through the scleral slit from the outside so that the distal tube ends distal to the Trabecular Meshwork in the anterior chamber of the eye. Towards the proximal end, the tube exits the sclera, lays on top of it, and connects on its proximal end to a plate that is fixated by sutures to the outside scleral surface far away (>10 mm) from the limbus.
• FIGS. 33-39 describes another ab externo method that uses a deployment device. In this method, a distal portion of the deployment device includes ahollow shaft209 that has a sharpened tip (FIG. 33). Ashunt212 resides within theshaft209. Thedistal shaft209 is advanced into the eye and into thesclera8 until a proximal portion of the shaft resides in theanterior chamber210 and a distal portion of theshaft209 is inside the scleral8 (FIGS. 34-36). Deployment of theshunt212 that is located inside theshaft209 is then accomplished by a mechanism that withdraws theshaft209 while theshunt212 is held in place by aplunger211 behind the proximal end of the shunt212 (FIGS. 37-39). As the implantation sequence progresses, theshaft209 is completely withdrawn from thesclera8. After that, theplunger211 is withdrawn from thesclera8, leaving theshunt212 behind with its distal end inside thesclera8, its proximal end inside theanterior chamber210, and apassageway214 through thesclera8. In a preferred embodiment theshaft209 is placed inside asleeve213 that is dimensioned in length relative to theshaft209 such that it will act as stopper during the penetration of theshaft209 into the eye and at the same time assures controlled longitudinal placement of theshunt212 relative to the outer surface of the eye. Thesleeve213 may be beveled to match the anatomical angle of the entry site surface.
• The shaft penetrates the conjunctival layer before it enters and penetrates the sclera. This causes a conjunctival hole that could create a fluid leakage after the shunt placement has been completed. To minimize the chance for any leakage, a small diameter shaft is used that results in a self-sealing conjunctival wound. To further reduce the chance for a conjunctival leak, a suture can be placed in the conjunctiva around the penetration area after the shunt placement.
• Furthermore the preferred method of penetrating the conjunctiva is performed by shifting the conjunctival layers from posterior to the limbus towards the limbus, using e.g. an applicator such as a Q-tip, before the shaft penetration is started. This is illustrated inFIGS. 40-41. That figure shows that anapplicator257 is put onto theconjunctiva258, about 6 mm away from the limbus. The loose conjunctiva layer is then pushed towards the limbus to create folding tissue layers that are about 2 mm away from the limbus. Thedevice shaft209 is now inserted through the conjunctiva andsclera8 starting about 4 mm away from the limbus. After the shunt placement has been completed, the Q-tip is released and the conjunctival perforation relaxes back from about 4 mm to about 8 mm limb at distance. This can cause the conjunctival perforation to be 4 mm away from the now slowly starting drainage exit. This distance will reduce any potential for leakage and allows for a faster conjunctival healing response. Alternative to this described upward shift, a sideway shift of the conjunctiva or anything in between is feasible as well. In another embodiment of the ab externo method, a conjunctival slit is cut and the conjunctiva is pulled away from the shaft entry point into the sclera. After the shunt placement is completed, the conjunctival slit is closed again through sutures.
• In certain embodiments, since the tissue surrounding the trabecular meshwork is optically opaque, an imaging technique, such as ultrasound biomicroscopy (UBM), optical coherence tomography (OCT) or a laser imaging technique, can be utilized. The imaging can provide guidance for the insertion of the deployment device and the deployment of the shunt. This technique can be used with a large variety of shunt embodiments with slight modifications since the trabecular meshwork is punctured from the scleral side, rather than the anterior chamber side, in the ab externo insertion.
• In another ab externo approach, a superficial flap may be made in the sclera and then a second deep scleral flap may be created and excised leaving a scleral reservoir under the first flap. Alternatively, a single scleral flap may be made with or without excising any portion of the sclera.
• A shaft of a deployment device is inserted under the flap and advanced through the sclera and into an anterior chamber. The shaft is advanced into the sclera until a proximal portion of the shaft resides in the anterior chamber and a distal portion of the shaft is in proximity to the trabecular outflow. The deployment is then performed such that an outlet of the shunt is positioned proximate the second opening in the sclera so that at least some of the fluid that exits the shunt flows through the first opening in the sclera, thereby ensuring that the intrascleral space does not become overwhelmed with fluid output from the shunt. At the conclusion of the ab externo implantation procedure, the scleral flap may be sutured closed. The procedure also may be performed without suturing.
• Regardless of the implantation method employed, some embodiments of the methods disclosed herein recognize that the proximity of the distal end of the shunt to the scleral exit slit affects the flow resistance through the shunt, and therefore affects the intraocular pressure in the eye. For example, if the distal end of theshunt212 is flush with the sclera surface then there is no scleral channel resistance (FIG. 42). In this embodiment, total resistance comes from theshunt212 alone. In another embodiment, if the distal end of theshunt212 is about 200 μm to about 500 μm behind the scleral exit, then the scleral slit closes partially around the exit location, adding some resistance to the outflow of aqueous humor (FIG. 43). In another embodiments, if the distal end of theshunt212 is more than about 500 microns behind the scleral exit, than the scleral slit closes completely around the exit location with no backpressure and opens gradually to allow aqueous humor to seep out when the intraocular pressure raises e.g. above 10 mmHg (FIG. 44). The constant seepage of aqueous humor keeps the scleral slit from scaring closed over time.
• Effectively, shunt placement according to some embodiments of the methods disclosed herein achieve a valve like performance where the scleral slit in front of the distal shunt end acts like a valve. The opening (cracking) pressure of this valve can be adjusted by the outer shunt diameter and its exact distal end location relative to the scleral exit site. Typical ranges of adjustment are 1 mmHg to 20 mmHg. This passageway distance can be controlled and adjusted through the design of the inserting device as well as the shunt length and the deployment method. Therefore a specific design can be chosen to reduce or prevent hypotony (<6 mmHg) as a post-operative complication.
INCORPORATION BY REFERENCE
• References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes.
EQUIVALENTS
• It is understood that the specific order or hierarchy of steps in the processes disclosed is an illustration of exemplary approaches. Based upon design preferences, it is understood that the specific order or hierarchy of steps in the processes may be rearranged. Some of the steps may be performed simultaneously. The accompanying method claims present elements of the various steps in a sample order, and are not meant to be limited to the specific order or hierarchy presented.
• Terms such as “top,” “bottom,” “front,” “rear” and the like as used in this disclosure should be understood as referring to an arbitrary frame of reference, rather than to the ordinary gravitational frame of reference. Thus, a top surface, a bottom surface, a front surface, and a rear surface may extend upwardly, downwardly, diagonally, or horizontally in a gravitational frame of reference.
• Furthermore, to the extent that the term “include,” “have,” or the like is used in the description or the claims, such term is intended to be inclusive in a manner similar to the term “comprise” as “comprise” is interpreted when employed as a transitional word in a claim.
• The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.
• A reference to an element in the singular is not intended to mean “one and only one” unless specifically stated, but rather “one or more.” Pronouns in the masculine (e.g., his) include the feminine and neuter gender (e.g., her and its) and vice versa. The term “some” refers to one or more. Underlined and/or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with the interpretation of the description of the subject technology. All structural and functional equivalents to the elements of the various configurations described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.
• While certain aspects and embodiments of the inventions have been described, these have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel methods and systems described herein may be embodied in a variety of other forms without departing from the spirit thereof. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the inventions.

Claims (1)

What is claimed is:

1. A method comprising inserting, through a cornea, an implant in an eye having (i) an anterior chamber and (ii) a sclera, to form a channel through the sclera and thereby establish fluid communication between the anterior chamber and the channel, and administering a pharmaceutical or biological agent to the eye.

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