Patent Application
20230414409
The present invention relates to stents for the relief of intraocular pressure in patients with glaucoma, and in particular to stents with one or more sealed channels that may be opened following placement of the stent.
Glaucoma is a group of eye diseases characterized by optic neuropathy, which may or may not be accompanied by raised intraocular pressure (IOP). Glaucoma is the leading cause of irreversible blindness in the world. The primary goal of treatment is to lower the IOP by means of medicines or surgical procedures.
Drainage of aqueous fluid is the cornerstone of glaucoma surgery. In this regard there is a trend towards replacing conventional trabeculectomy with stents, so-called micro-invasive glaucoma surgery (MIGS). This surgical option is particularly appealing to treat patients in the gap between early and advanced glaucoma. Notably, when draining fluid from the anterior chamber to a second reservoir, the anterior chamber pressure is regulated by the combined outflow resistance through the stent and out of the second reservoir.
The first MIGS device approved by the US Food and Drug Administration was the iStent (Glaukos; CA, USA). The iStent creates a bypass pathway through the trabecular meshwork. The remaining outflow resistance is provided by the scleral aqueous channels and intrascleral veins. As each stent increases the access to collector channels and fluid outflow, an additional reduction in IOP can be seen after implantation of two or more devices. Theoretically, the iStent has a lower limit for reducing the IOP similar to the episcleral venous pressure, which is approximately 10 mm Hg.
An alternative to bypassing the trabecular meshwork is to create a subconjunctival drainage pathway. In contrast to the scleral aqueous channels, a healthy conjunctiva provides minimal subconjunctival outflow resistance, and the potential for reducing the intraocular pressure is therefore higher than that of the iStent. An example of a device that creates drainage into the subconjunctival space is the XEN®45 Gel Stent (Allergan; Dublin, Ireland). This stent and devices for its insertion are described in U.S. Pat. Nos. 6,007,511; 8,663,303; 8,721,702; 8,765,210; 8,852,136; 8,852,256; 9,017,276; 9,192,516; 9,095,413; 9,113,994; each of which is incorporated by reference herein in its entirety.
A second alternative to bypassing the trabecular meshwork is to create a suprachoroidal drainage pathway, which utilizes the pressure difference between the anterior chamber and the suprachoroidal space to lower the TOP.
Inevitably, the necessary outflow resistance of a tube draining subconjunctivally restricts its full TOP lowering potential. Consequently, the target TOP may not be met. Moreover, glaucoma is a chronic disease, and the TOP may increase over time despite an initially successful stent procedure. The trend towards MIGS stents in glaucoma notwithstanding, additional surgical or medical therapy is often necessary and increases the burden of treatment. The present invention solves this problem by providing a multilumen stent with sealed secondary channels, which may be opened according to need to further lower the outflow resistance of the stent and, thus, the TOP.
The present invention relates to stents for the relief of TOP in patients with glaucoma, and in particular to stents with one or more sealed secondary channels, which may be opened following placement of the stent.
In some preferred embodiments, the present invention provides glaucoma microstents for minimally invasive glaucoma surgery comprising: a microstent with proximal and distal ends, the microstent having therein at least one open channel that extends between the proximal and distal ends, at least one open channel having openings at both the proximal and distal ends to allow fluid flow therethrough, the microstent further having therein at least one sealed channel that extends between the proximal and distal ends, the at least one sealed channel having an opening at the distal end and a seal at the proximal end to prevent fluid flow therethrough.
In some preferred embodiments, the microstent comprises from 2 to 7 sealed channels. In some preferred embodiments, the microstent comprises one open channel.
In some preferred embodiments, the microstent comprises from 2 to 5 sealed channels. In some preferred embodiments, the microstent comprises one open channel.
In some preferred embodiments, the microstent comprises from 2 to 3 sealed channels. In some preferred embodiments, the microstent comprises one open channel.
In some preferred embodiments, the microstent comprises 2 sealed channels. In some preferred embodiments, the microstent comprises one open channel.
In some preferred embodiments, each of the channels of the microstent is sized to provide a flow resistance of from 0.5 to 8.0 mm Hg.
In some preferred embodiments, each of the channels of the microstent is sized to provide a flow resistance of from 0.5 to 5.0 mm Hg.
In some preferred embodiments, each of the channels of the microstent is sized to provide a flow resistance of from 0.5 to 3.5 mm Hg.
In some preferred embodiments, the combined channels in the microstent provide a flow resistance of from 0.5 to 10 mm Hg when open.
In some preferred embodiments, the channels in the microstent are parallel. In some preferred embodiments, the channels in the microstent are circular in cross section. In some preferred embodiments, the microstent is tubular in shape. In some preferred embodiments, the proximal end of the stent comprises a rim portion that extends past the terminal ends of the channels.
In some preferred embodiments, the microstent is formed from a polymer. In some preferred embodiments, the polymer is selected from the group consisting of silicone, cross-linked polyvinyl alcohol (PVA) hydrogel, cross-linked PVA hydrogel foam, polyurethane, polyamide, styrene isobutylene-styrene block copolymer (Kraton), polyethylene terephthalate, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, and polytetrafluoroethylene.
In some preferred embodiments, the stent is formed from a gel material. In some preferred embodiments, the gel material is a cross-linked gelatin.
In some preferred embodiments, the stent is 3D printed in a suitable biocompatible material.
In some preferred embodiments, the seal is a membrane. In some preferred embodiments,
the membrane is formed from a material selected from the group consisting of silicone, polyurethane, polyamide, styrene isobutylene-styrene block copolymer (Kraton), polyethylene terephthalate, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, and polytetrafluoroethylene. In some preferred embodiments, said membrane is non-transparent or opaque. In some preferred embodiments, said membrane is colored to enhance absorption of the light wave emitted from a laser.
In some preferred embodiments, the present invention provides methods of treating glaucoma in a subject in need thereof comprising: inserting a glaucoma microstent as described above into the eye of a subject so that the proximal end of the microstent is located in the anterior chamber of the eye and the distal end is located in a portion of the eye allowing drainage into the subconjunctival space of the eye so that intraocular pressure in the anterior chamber is reduced due to the flow of fluid through the open channel of the glaucoma microstent. In some preferred embodiments, the portion of eye allowing drainage into the subconjunctival space is the intra-Tenon's space. In some preferred embodiments, the methods further comprise the step of applying energy to the seal at the proximal end of one or more of the sealed channels to ablate the seal thereby allowing fluid flow from the previously sealed channel to further decrease intraocular pressure. In some preferred embodiments, the methods further comprise evaluating TOP prior to removal of the seal. In some preferred embodiments, the methods further comprise removing seals from the channels in a serial manner to achieve a desired reduction of TOP. In some preferred embodiments, the microstent is inserted with an ab interno approach.
In some preferred embodiments, the present invention provides a combined microstent and injection device comprising a microstent as described above inserted into a hollow shaft having a proximal end and a distal end. In some preferred embodiments, the microstent is positioned in the hollow shaft so that the distal end of the microstent is aligned with the distal end of the hollow shaft. In some preferred embodiments, the proximal end of the hollow shaft is connected to an ejector and the distal end is configured to allow ejection of the microstent from the hollow shaft upon deployment of the ejector. In some preferred embodiments, the device is provided in a sterile package.
The present invention relates to stents for the relief of IOP in patients with glaucoma, and in particular to stents with one or more sealed secondary channels that may be opened following placement of the stent.
Glaucoma is a group of eye diseases that damage the optic nerve. A main risk factor for glaucoma is elevated IOP. Elevated IOP is due to a buildup of a fluid (aqueous humor) that flows throughout the inside of the eye. This internal fluid normally drains out through a tissue called the trabecular meshwork at the angle where the iris and cornea meet. When fluid is overproduced or the drainage system doesn't work properly, the fluid can't flow out at its normal rate and the IOP increases. Glaucoma commonly affects both eyes, and without appropriate IOP-lowering treatment, it progressively damages the visual field and results in tunnel vision and ultimately blindness.
Various stents have been developed to relieve IOP to treat glaucoma in a procedure known as micro-invasive glaucoma surgery (MIGS). One example of a glaucoma stent is the XEN® Gel stent (Allergan; Dublin, Ireland), see, e.g., U.S. Pat. Nos. 6,007,511; 8,663,303; 8,721,702; 8,765,210; 8,852,136; 8,852,256; 9,017,276; 9,192,516; 9,095,413; 9,113,994; each of which is incorporated by reference herein in its entirety. Regardless of stent type, the crucial goal of MIGS is to provide sufficient long-term outflow of fluid without causing ocular hypotony. Because of its minimal outflow resistance, the risk of hypotony is particularly relevant when draining fluid to the subconjunctival space. Accordingly, the outflow resistance through the stent must provide a sufficient safety margin.
Current glaucoma stents used for MIGS generally comprise a single channel. Inevitably, the necessary outflow resistance of a tube draining subconjunctivally restricts its full IOP lowering potential. Consequently, the target IOP may not be met. Moreover, glaucoma is a chronic disease, and the IOP can increase over time despite an initially successful stent procedure. The trend towards MIGS stents in glaucoma notwithstanding, additional surgical or medical therapy is often necessary and increases the burden of treatment.
The present invention addresses this problem by providing a novel glaucoma stent for MIGS with multiple channels wherein one or more of the channels are reversibly sealed so that the sealed channel may be opened at a later time by means of a simple laser procedure to allow additional IOP relief. In this way, the IOP lowering potential of the original MIGS procedure can be heightened stepwise according to need, thereby improving the prospect of the stent for successful long-term glaucoma monotherapy without hypotony. Because opening of each secondary channel will further decrease the outflow resistance, the efficacy of the stent can be up-titrated with a minimally invasive laser procedure to safely achieve the desired TOP.
As depicted in
The size of the primary and secondary channels may be varied to provide desired fluid flow levels and TOP reduction. Appropriate channel dimensions can be determined using the Hagen-Poiseuille equation; the depending factors are the length and inner diameter of the tube, the aqueous fluid production rate (approximately 2 μl/min), and the aqueous fluid viscosity (approximately 0.72 mPa·s at 36° C.). In some preferred embodiments, the channels (and thus the microstent) are from about 2 to 10 mm in length, preferably from about 4 to 8 mm in length and most preferably about 6 mm in length. In some preferred embodiments, the inner diameter of the channels is from about 10 to 60 μm, more preferably from about 20 to 50 μm, and most preferably from about 35 to 50 μm. In any event, it will be recognized that the length and diameter may be varied to provide the preferred fluid flow. Thus, in some embodiments, each of the channels are sized to provide a flow resistance from to 8.0 mm Hg, more preferably from 0.5 to 5.0 mm Hg, and most preferably from 0.5 to 3.5 mm Hg. In some embodiments, the combined channels provide a total flow resistance of the stent from 0.5 to 20 mm Hg, more preferably from 0.5 to 15 mm Hg, and most preferably from 0.5 to 10 mm Hg.
The microstents of the present invention may be formed from any suitable material. In some embodiments, the microstents are formed from a biocompatible polymer or other biocompatible material. Suitable biocompatible materials and polymers include, but are not limited to, cross-linked gelatin hydrogel (e.g., cross-linked with glutaraldehyde), silicone, cross-linked polyvinyl alcohol (PVA) hydrogel, cross-linked PVA hydrogel foam, polyurethane, polyamide, styrene isobutylene-styrene block copolymer (Kraton), polyethylene terephthalate, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or other biocompatible polymeric material, or mixture of copolymers thereof; polyesters such as polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate or other biodegradable polymer, or mixtures or copolymers thereof.
The seals utilized in the microstents of the present invention may be formed from any suitable material. In general, the material should be chosen so that it can be ablated by lasers used in optical surgeries such as argon and YAG lasers. In some embodiments, it is contemplated that the laser membranotomy procedure is analogous to routine argon laser trabeculoplasty or YAG laser capsulotomy for posterior capsule opacification. Suitable seals include membranes formed from biocompatible polymers, such as those listed above.
The microstents of the present invention are preferably used to reduce IOP in a subject in need thereof. Suitable subjects include human patients, as well as animal subjects such as companion animals, e.g., dogs, cats, horses, and the like. In some preferred embodiments, the microstents of the present invention are deployed into an eye such that the stent forms a passage from the anterior chamber of the eye to the intra-Tenon's space. Deployment of the stent such that the inlet terminates in the eye's anterior chamber and the outlet terminates in the intra-Tenon's space safeguards the integrity of the conjunctiva to allow subconjunctival drainage pathways to successfully form. The conjunctiva is protected from direct contact with the shunt by Tenon's capsule. Additionally, drainage into the intra-Tenon's space provides access to more lymphatic channels than just the conjunctival lymphatic system, such as the episcleral lymphatic network. Moreover, deployment of the stent so that the outlet terminates in the intra-Tenon's space avoids having to pierce Tenon's capsule which can otherwise cause complications during glaucoma filtration surgery due to its tough and fibrous nature.
In some preferred embodiments, the stents are inserted using an ab interno glaucoma treatment procedure. Ab interno approaches for implanting an intraocular stent 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, a surgical intervention to implant the stent involves inserting into the eye a deployment device that holds the microstent and deploying the stent within the eye. A deployment device holding the stent enters the eye through the cornea (ab interno approach). The deployment device is advanced across the anterior chamber in what is referred to as a transpupillary implant insertion. The deployment device is advanced through the sclera until a distal portion of the device is in proximity to the subconjunctival space. The stent 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.
Thus, in some preferred embodiments, the present invention provides a deployment device comprising a hollow shaft configured to hold the microstent, as described herein. In preferred embodiments depicted in
As indicated above, the secondary channels of the microstents of the present invention can be activated by a laser pulse focused on the thin membrane sealing the opening in the eye's anterior chamber. Intuitively, the laser procedure is similar to standard argon laser trabeculoplasty. This process is depicted schematically in
Accordingly, in some embodiments, the present invention provides methods for treating glaucoma in a subject in need thereof comprising inserting a microstent of the invention into the eye of the subject so that fluid drains from the anterior chamber of the eye thereby reducing IOP. In some embodiments, the microstent is inserted by an ab interno approach. In some preferred embodiments, the microstent is placed so that the proximal end of the microstent comprising the channel seals is located in the anterior chamber of the eye and the distal end of the microstent is located so that fluid from the eye can ultimately drain into the subconjunctival space. In some preferred embodiments, the distal end is placed in the intra-Tenon's space.
In some embodiments, the methods of the present invention further comprise evaluating IOP after placement of the microstent. In some embodiments, if additional IOP reduction is required, the energy is applied to one or more of the seals to ablate or remove the seals to achieve the desired amount of IOP reduction. In some embodiments, the removal of the seals may be performed in a serial manner (i.e., one at a time) and IOP is measured after each seal is removed until the desired reduction in IOP is achieved. As described above, in preferred embodiments, the seals are removed by application of energy from a laser, such as an argon or YAG laser, although any other suitable means of removal of the seals may be employed.
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.
The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
A three-lumen glaucoma stent prototype was produced by Boston Micro Fabrication utilizing Projection Micro Stereolithography (POL) technology. The prototype was printed in HTL Resin, which has a translucent yellow colour. The membranes sealing two of three openings were printed as an integrated part of the stent and coloured post-print to absorb laser light. A slit lamp argon laser was then successfully used to individually puncture the membranes of the stent prototype.
A similar stent prototype as described in Example 1 was successfully implanted into an artificial eye from SimulEYE and a slit lamp argon laser was used to accurately puncture the membrane in gonioscopic view. A single laser pulse was sufficient to puncture one membrane. This experiment simulates the actual clinical procedure that uptitrates the pressure-lowering effect of the multilumen glaucoma stent.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2021/000823 | 11/23/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63118113 | Nov 2020 | US |
