A system for the formation and preparation of implantable biological stents and biological materials in the treatment of glaucoma.

Abstract

To provide a device and method for glaucoma treatment without causing ocular tissue damage.SOLUTION: A system for preparation and insertion of an implant 105 into an eyeball includes a handle having one or more actuators and an elongated shaft having an outer sheath 1318 and an elongate member 1320 positioned within a lumen 1328 of the tubular outer sheath. The system includes a recess 1321 sized for holding a patch 101 of material fixed relative to the handle and a cutting member 1312 movable relative to the handle and to the recess. The cutting member cuts the patch of material into an implant as the cutting member moves towards a cutting configuration. The implant, once cut, is axially aligned with the lumen of the tubular outer sheath. The inner elongate member is movable relative to the tubular outer sheath to advance the implant into a deployment position in the lumen of the tubular outer sheath for delivery into the eyeball. Related devices and methods are provided.SELECTED DRAWING: Figure 16B

Description

Cross - reference to related applications

[0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application 62 / 861,900, filed on June 14, 2019, 62 / 897,570, filed on September 9, 2019, and 62 / 943,106, filed on December 3, 2019. The disclosures of the provisional applications are hereby incorporated by reference in their entireties.

Background Art

[0002] The mainstay of glaucoma eye surgery is to enhance the aqueous humor outflow from the eye. Such surgeries have various approaches as follows: 1) ab externo trabeculectomy or shunt, which requires cutting the conjunctiva and sclera to penetrate the eye and provide an episcleral outflow pathway; 2) ab interno trabecular or trans - scleral outflow stenting or aqueous humor shunt using hardware - based implantable devices or excisable and non - implantable cutters such as dual - blade and trabectome; and 3) ab interno supraciliary stenting using implantable non - biological hardware implants.

[0003] Current ab interno stent devices and methods are based on non - biological hardware materials such as polyimide, polyethersulfone, titanium, polystyrene - block - isobutylene - block - styrene. Such non - biological hardware - based implantable devices may cause eye tissue damage such as significant erosion, fibrosis, and endothelial cell loss, and there are significant drawbacks.

[0004] From the above perspectives, there is a need for improved devices and methods related to eye surgery for the treatment of glaucoma.

Summary of the Invention

[0005] This disclosure relates to methods and apparatus for reducing, regulating, or otherwise modulating intraocular pressure within an eyeball by implanting a minimally invasive bioprosthetic stent within the eyeball. In exemplary embodiments, a bioprosthetic implant, such as a bioprosthetic stent, shunt, or implant, is implanted into the eye so that the stent is at least partially positioned on the choroidal, transscleral, and / or supraciliary locations within the eyeball, in order to treat glaucoma. The stent may be implanted into the eyeball via an internal delivery pathway using a delivery device configured for such a delivery pathway. In exemplary embodiments, the stent assists or otherwise provides drainage of aqueous humor from the anterior chamber to the uveoscleral outflow pathway of the eye. The stent provides a fluid passage between the anterior chamber and the suprachoroidal and / or supraciliary spaces. The stent provides two independent, but potentially cooperative, fluid passages / outflow pathways, such as by stenting the supraciliary fissure and by using a hydrophilic biological material that allows transinfiltration flow through the material itself. Other drainage routes are thought to include those via Schlemm's canal or subconjunctival location.

[0006] In one embodiment, a system for preparing an implant and inserting the implant into the eyeball is provided. The system includes a handle having one or more actuators; an elongated shaft extending distally from the handle; the elongated shaft having a tubular outer sheath and an inner elongated member positioned within the lumen of the tubular outer sheath; a recess sized for holding a patch of material fixed to the handle; and a cutting member movable relative to the handle and recess to a cutting configuration. As the cutting member moves toward the cutting configuration, it cuts the patch of material into the implant. Once cut, the implant aligns axially with the lumen of the tubular outer sheath. The inner elongated member is movable relative to the tubular outer sheath to advance the implant to an deployed position within the lumen of the tubular outer sheath for delivery into the eyeball.

[0007] The material patch may include biologically derived materials suitable for implantation into the eyeball. Biologically derived materials may include tissue harvested from a donor or eyeball. Biologically derived materials may be autografts, allografts, or xenografts. The material may be engineered tissue. The artificial tissue may be 3D printed material suitable for implantation. Biologically derived materials may have a permeable and / or rigid structure that allows for aqueous outflow from the eye when the implant, excised from the material patch, is placed within the annular dialysis fissure. The implant, excised from the material patch, may be bioabsorbable or non-bioabsorbable.

[0008] The implant may contain one or more therapeutic agents. One or more therapeutic agents may include antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport / migration inhibitors, antiglaucoma agents, prostaglandin analogs, carbonic anhydrase inhibitors, neuroprotective agents, antibiotics, antivirals, antiallergic agents, anti-inflammatory agents, pupillary dilators, or immunomodulators.

[0009] The material patch can be compressed and / or tensioned before the cutting member is moved to the cutting configuration. The material patch can be compressed between two biased planar surfaces that prevent movement of the material patch during subsequent cutting using the cutting member. The material patch can be tensioned by a pair of flexible stretcher legs configured to apply tensile force away from the centerline of the material patch.

[0010] The system may further include a cartridge detachably coupled to the area of ​​the handle. The cartridge may include a base and a cover. The recess may be located within the base of the cartridge. The recess may be positioned within the handle. The system may further include an access door coupled to the handle and configured to enclose the recess when rotated to a closed configuration and to expose the recess when rotated to an open configuration. The access door may be formed of a transparent or translucent material. The system may further include a projection extending upward from the centerline of the recess, forming two channels within the recess on either side of the projection. This projection can bias the centerline of a patch of material upward toward the door. When the access door is rotated to a closed configuration relative to the handle, the patch of material can be trapped between the projection and the access door. The access door may be configured to apply tension to the patch of material when the access door is in a closed configuration. The access door may include an actuator configured to apply tension. The actuator may include a pair of flexible stretcher legs configured to extend into the recess. A pair of flexible stretcher legs may include a first leg that contacts the patch of material on a first side of the centerline and a second leg that contacts the patch of material on the opposite side of the centerline. When the pair of stretcher legs are further propelled into a recess by an actuator that stretches the patch of material relative to the centerline, the first leg and the second leg can be propelled outward and away from each other.

[0011] At least the proximal portion of the elongated shaft can extend along the longitudinal axis. The distal end region of the elongated shaft can be angled away from the longitudinal axis. The distal end region of the elongated shaft can have a maximum outer diameter not exceeding approximately 1.3 mm. The most distal end of the elongated shaft can be blunted to allow for dissection of inter-tissue in the eye without cutting the tissue. The tubular outer sheath can be a hypotube with an inner diameter of approximately 0.036 inches to less than approximately 0.009 inches. The implant cut from the patch of material can have dimensions that substantially fill the inner diameter of the tubular outer sheath.

[0012] A tubular outer sheath is coupled to a first actuator, and an inner elongated member can be coupled to a second actuator. The first actuator may be positioned on the underside of a handle configured to retract the tubular outer sheath proximally, and the second actuator may be positioned on the upper surface of a handle configured to advance the inner elongated member distally. Distal advancement of the inner elongated member can propel the implant distally through the lumen of the tubular outer sheath to a primed position near the distal opening from the lumen of the tubular outer sheath. With the inner elongated member stationary relative to the handle, retracting the tubular outer sheath proximally allows the implant to be detached from the elongated shaft and deployed in the eyeball.

[0013] The tubular outer sheath can be a movable introduction tube that passes through the lumen of a fixed outer tube. The inner elongated member can be movable within the introduction tube. The introduction tube can be more flexible than the inner elongated member, and the inner elongated member can be more flexible than the fixed outer tube. The inner elongated member can relax so that when it retracts proximally, it takes the shape of the fixed outer tube, and when it extends distally from the outer tube, it returns to its curved shape. The introduction tube can conform to the curved shape of the inner elongated member when both the introduction tube and the inner elongated member extend distally from the outer tube.

[0014] In relation to the interrelated aspects, a cartridge is provided for use with a system for preparing the implant and inserting the implant into the eyeball from within. The cartridge includes a base having an upper surface that defines a recess of size and shape to receive a patch of material to be cut into the implant. The cartridge includes a cover that is movably coupled to the base between an open configuration and a closed configuration. The cover has a lower surface that is positioned to contact the upper surface of the base when the cover is in the closed configuration. The cartridge includes a cutting member that is movable to the cutting configuration relative to the base and relative to the recess. The cutting member cuts a patch of material into the implant as the cutting member moves toward the cutting configuration. Once cut, the implant is aligned axially with respect to the lumen of a tubular outer sheath for delivery into the eyeball.

[0015] When the cover is in a closed configuration, the material patch can be held fixedly to the base. When the cover is in a closed configuration, the material patch can be compressed within the recess. The cover can be configured to apply tension to the material patch compressed within the recess.

[0016] In related embodiments, methods are provided for preparing an implant for implantation in a patient's eye, and for inserting the implant into the patient's eye. The method includes inserting a patch of material into the proximal portion of an instrument. The instrument further includes a cutting member and a distal portion sized for insertion into the eyeball. The method includes cutting the patch with the cutting member to form an implant. The method includes advancing the implant from the proximal portion of the instrument to an unfolded position within the lumen of the elongated tubular member of the distal portion. The method includes inserting the distal portion of the instrument into the anterior chamber of the eyeball. The method includes positioning the distal portion adjacent to the ocular tissue and unfolding the implant from the instrument.

[0017] Inserting a patch of material may include inserting the patch into a recess in the proximal portion and closing a cover over the recess. The cover can be fitted to engage with at least a portion of the patch of material before cutting. At least a portion of the cover may be transparent. The cover can prevent the patch from moving while the patch is being cut by the cutting member. The method may further include tensioning at least a portion of the patch of material before cutting the patch. Tensioning a portion of the patch may include compressing a first portion and a second portion of the patch and tensioning a central portion of the patch, the central portion being located between the first and second portions. The central portion of the patch may include an implant when the patch is cut by the cutting member. Tensioning a portion of the patch may include activating an actuator to tension the portion of the patch. Activating the actuator may include rotating the actuator to tension the portion of the patch. The cover may include an actuator, and activation of the actuator tensions at least a portion of the patch. This method may further include inserting the distal portion of the instrument into the anterior chamber from the inside through a corneal incision, leaving the proximal portion of the instrument outside the eyeball. The material may be a biologically derived material suitable for implantation into the eyeball. The biologically derived material may be tissue harvested from a donor or patient, or autograft, allograft, or xenograft material. The material may be an engineered or 3D-printed material suitable for implantation. The implant may contain one or more therapeutic agents.

[0018] When the implant is deployed from the instrument, it can be positioned at least partially between the ciliary body and sclera of the patient's eye. The implant can be positioned between the ciliary body and sclera within a cyclodialysis hiatus. The cutting member may include a lumen, a distal opening, and a pair of opposing cutting blades. Cutting may include advancing the cutting member to cut a patch of material and capturing the implant within the lumen of the cutting member. The pair of opposing cutting blades may cut the patch in two places to separate the implant from the remainder of the patch. The inner diameter of the elongated tubular member may be substantially the same as the inner diameter of the lumen of the cutting member. The distal portion of the cutting member may be chamfered. The implant may include a longitudinal axis. The longitudinal axis of the implant may remain aligned with the longitudinal axis of the lumen of the elongated tubular member when the cutting member has finished cutting the patch and forming the implant.

[0019] Advancing the implant from the proximal portion of the instrument may include pushing the implant from the lumen of the cutting member into the lumen of the distal elongated tubular member. The distal end region of the elongated tubular member may have at least one of being angled, curved, or flexible. The method may further include acting a first actuator to tension at least a portion of the patch before cutting, acting a second actuator to advance the cutting member to cut the patch after tensioning, acting a third actuator to advance the implant to an unfolded position, and acting a fourth actuator to unfold the implant from the instrument, each actuator being operatively coupled to the instrument.

[0020] Positioning the distal portion adjacent to ocular tissue may include positioning the implant between the ciliary body and sclera while the implant remains at least partially within the lumen of the distal portion. Deploying the implant from the instrument may include retracting the elongated tubular portion from the implant while maintaining the implant's position relative to adjacent ocular tissue. The most distal end of the elongated tubular member may be blunted to allow dissection without cutting ocular tissue. Closing the cover over the recess may include engaging a portion of the cover with the first portion of the patch and tensing the second portion of the patch to compress the first portion of the patch.

[0021] Details of one or more modifications of the subject matter described herein are given in the accompanying drawings and the following description. Other features and advantages of the subject matter described herein will become apparent from the description and drawings, as well as the claims. [Brief explanation of the drawing]

[0022] These and other embodiments will now be described in detail with reference to the following drawings. In general, the drawings are not reduced to an absolute or relative proportion, but are intended as examples. The relative arrangement of features and elements may also be modified for illustrative purposes.

[0023] [Figure 1] This is a cross-sectional view of a human eye showing the anterior and posterior chambers of the eyeball with a stent positioned within the eyeball in an exemplary location. [Figure 2A] This shows an exemplary embodiment of a bone fenestration device for forming a stent. [Figure 2B] This shows an exemplary embodiment of a bone fenestration device for forming a stent. [Figure 3] This is a perspective view showing an exemplary embodiment of a delivery device. [Figure 4] This is a cross-sectional view of the delivery device. [Figure 5]An embodiment of a delivery device having a bone perforation fenestrated cartridge in an open configuration is shown. [Figure 6A] An embodiment of a delivery device having a bone perforation fenestrated cartridge in a closed configuration is shown. [Figure 6B] It is a cross-sectional view of the device of FIG. 6A along line B-B. [Figure 7] It is a partial view of a delivery device shaft having a patch of biologically-derived material extending through a cut-out window. [Figure 8A] It is a schematic top view of a cut-out window of a delivery device shaft. [Figure 8B] It is a cross-sectional view of FIG. 8A along line B-B. [Figure 9A] It is a perspective view of an embodiment of a bone perforation fenestrated cartridge. [Figure 9B] It is a cross-sectional view of the bone perforation fenestrated cartridge of FIG. 9A. [Figure 9C] It is a perspective view of the base of the bone perforation fenestrated cartridge of FIG. 9A. [Figure 10A] It is a perspective view of the bone perforation fenestrated cartridge of FIG. 9A with respect to a cutting member. [Figure 10B] It is a cross-sectional view of the bone perforation fenestrated cartridge of FIG. 10A with a cutting member partially inserted. [Figure 10C] It is a cross-sectional view of the bone perforation fenestrated cartridge of FIG. 10A with a cutting member fully inserted. [Figure 11A] It is a side view of a cutting member of FIG. 9A showing a blade with respect to a delivery device shaft loaded with a patch of biologically-derived material. [Figure 11B] It is a perspective view of the cutting member of FIG. 11A with the housing removed. [Figure 11C] It is a side view of a blade with respect to a delivery device shaft and a cut stent. [Figure 11D] It is a side view of a cut stent placed within the lumen of a delivery device shaft. [Figure 11E] It is a distal end view of a delivery device shaft having a tubular outer sheath and an inner elongated member or pusher. [Figure 12A] This shows the distal end region of the delivery device. [Figure 12B] This shows the distal end region of the delivery device. [Figure 13A] This is a top view of an embodiment of a delivery device. [Figure 13B] Figure 13A is a bottom view of the delivery device. [Figure 14A] Figure 13A is a partial view of the delivery device. [Figure 14B] Figure 13A is a partial view of the delivery device. [Figure 15A] This is a schematic diagram showing a stretcher that applies tension to a patch of material. [Figure 15B] This is a schematic diagram showing a stretcher that applies tension to a patch of material. [Figure 15C] This is a schematic diagram showing a stretcher that applies tension to a patch of material. [Figure 16A] This is a schematic diagram of a cutter tube used to cut material patches. [Figure 16B] This is a schematic diagram of a cutter tube used to cut material patches. [Figure 17A] This is a schematic diagram of a pusher used to insert a severed stent within the delivery shaft. [Figure 17B] This is a schematic diagram of a pusher used to insert a severed stent within the delivery shaft. [Figure 18A] This is a top view of an embodiment of a delivery device. [Figure 18B] Figure 18A is a bottom view of the delivery device. [Figure 19A] Figure 18A is a partial view of the delivery device. [Figure 19B] Figure 18A is a partial view of the delivery device. [Figure 20A] This shows a stretcher configured to apply tension to a patch of material. [Figure 20B] This shows a stretcher configured to apply tension to a patch of material. [Figure 20C]This shows a stretcher configured to apply tension to a patch of material. [Figure 21] Figure 18A is a cross-sectional view of the delivery device showing the stretcher. [Figure 22] This is a partial view of the cutter tube as it passes through the apparatus shown in Figure 18A. [Figure 23A] Figure 22 is a detailed partial view of the cutter tube. [Figure 23B] Figure 22 is a detailed partial view of the cutter tube. [Figure 23C] Figure 22 is a detailed partial view of the cutter tube. [Figure 23D] Figure 22 is a detailed partial view of the cutter tube. [Figure 24A] Figure 18A shows a partial cross-sectional view of a severed stent being ejected from the delivery shaft. [Figure 24B] Figure 18A shows a partial cross-sectional view of a severed stent being ejected from the delivery shaft. [Figure 24C] Figure 18A shows a partial cross-sectional view of a severed stent being ejected from the delivery shaft. [Figure 25] Figure 18A is a partial cross-sectional view showing the forward mechanism for various axially movable components of the apparatus. [Figure 26] This is a partial cross-sectional view showing the retraction mechanism for the introduction tube of the apparatus in Figure 18A.

[0024] Please understand that the drawings are for illustrative purposes only and are not intended to be to scale. Please also understand that the devices described herein may include features not necessarily depicted in each drawing. [Modes for carrying out the invention]

[0025] Disclosed are implants, systems, and methods for increasing fluid outflow from the anterior chamber of the eye. As described in detail below, internal outflow stents using biological, cell-based, or tissue-based materials provide biocompatible fluid outflow enhancement with improved tolerability and safety compared to conventional shunts. In exemplary embodiments, biological tissue or bio-derived material is harvested or generated in vitro and formed into an implant, also referred to herein as a stent, using a bone drilling fenestration device or cutting tool. In embodiments, the stent is an elongated body or strip of tissue that does not have an internal lumen. Lumen-based devices may be limited by the lumen acting as a pathway for fibrous occlusion. The stent formed from tissue is then implanted into the eyeball via an internal delivery pathway to provide fluid flow from the anterior chamber. The stents described herein can be used as an adjunct to phacoemulsification or as a standalone treatment for glaucoma as part of minimally invasive glaucoma surgery (MIGS) treatment.

[0026] The use of terms such as stent, implant, shunt, biological tissue, or tissue is not intended to limit any single structure or material. The implanted structure may, but does not have to be, be made of a material that is substantially absorbed into the ophthalmic tissue after being placed in the eyeball, such that once absorbed, a space may remain where the structure was previously located. Once implanted, the structure may also remain in place for a long period of time and not be substantially eroded or absorbed.

[0027] As will be described in more detail below, the stents described herein can be manufactured from biologically derived materials that, once implanted in a patient, do not cause toxicity or harm.

[0028] The term “biologically derived materials” includes naturally occurring and synthetically produced biological materials and combinations thereof that are suitable for transplantation into the eyeball. Biologically derived materials include materials that are natural biological structures having a biological arrangement naturally found within mammalian subjects, including organs or parts of organs formed from tissue, and tissues formed from materials grouped according to structure and function. Biologically derived materials include tissues such as corneal tissue, scleral tissue, or cartilage tissue. The tissues considered herein may include any of the various tissues, including muscle, epithelium, connective tissue, and nerve tissue. Biologically derived materials include tissues, organs, parts of organs, and tissues from subjects that are suitable for transplantation, including autografts, allografts, and xenografts, taken from a donor or patient. Biologically derived materials include naturally occurring biological materials, including any material that naturally exists within the body of a mammal. Biologically derived materials as used herein also include materials that have been manipulated to have a biological arrangement similar to that of natural biological structures. For example, materials may be synthesized using in vitro techniques, such as seeding appropriate cells, engineered, or 3D-printed materials into a three-dimensional scaffold or matrix to form a biostructure suitable for transplantation. Biologically derived materials as used herein also include cell-derived materials, including stem cell-derived materials.

[0029] The biologically derived materials used to form stents, sometimes referred to herein as biological tissue or biomaterial, are diverse and may include, for example, corneal tissue, scleral tissue, cartilage tissue, collagenous tissue, or other rigid biological tissues. Biological tissues can be hydrophilic or hydrophobic. Biological tissues may contain or be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

[0030] Non-biological materials include synthetic materials that are biocompatible but not cell-based or tissue-based, and are prepared by artificial synthesis, processing, or manufacturing. For example, non-biological materials include polymers, copolymers, polymer blends, and plastics. Non-biological materials include inorganic polymers such as silicone rubber, polysiloxanes, and polysilanes, and organic polymers such as polyethylene, polypropylene, polyvinyl, and polyimide.

[0031] Regardless of the source or type of biologically derived material, the material can be cut or trephine into an elongated shape suitable for stent placement and implantation in the eyeball. This bone fenestration process of the tissue can be performed before or during the surgical implantation process. The stent implanted in the eye may have a structure and / or permeability that allows for water outflow from the anterior chamber when positioned within the annular dialysis fissure.

[0032] Figure 1 is a cross-sectional view of a human eye showing the anterior chamber (AC) and posterior chamber (PC). Stent 105 can be positioned inside the eye at the implanted location such that at least a first portion of stent 105 is positioned within the anterior chamber (AC) and a second portion of stent 105 is positioned within tissue such as the supraclavicular space and / or suprachoroid space of the eye. Stent 105 is of a size and shape that allows it to be positioned in such a configuration. Stent 105 provides, or otherwise functions as, a passage for the flow of aqueous humor away from the anterior chamber (AC) (e.g., towards the supraclavicular space and / or suprachoroid space). In Figure 1, stent 105 is schematically represented as an elongated body. It should be understood that the size and shape of stent 105 may vary.

[0033] Stent 105 can be implanted internally, for example, through a clear corneal or scleral incision. The stent can be implanted to form a communication between the anterior chamber AC and the suprabillary space, between the anterior chamber AC and the supchoroidal space, between the anterior chamber AC and Schlemm's canal, or between the anterior chamber AC and the subconjunctival space. In a preferred embodiment, stent 105 is implanted with its distal end positioned in the suprabillary location and its proximal end positioned in the anterior chamber AC to provide a suprabillary fissure. The distal end of stent 105 can be positioned between other anatomical parts of the eye.

[0034] Conventional glaucoma stent devices are typically made of non-biological materials such as polyimide or other synthetic materials, which can cause endothelial tissue damage leading to progressive, long-term, and irreversible corneal endothelial loss. The stent materials described herein can reduce and / or eliminate these risks of tissue damage while still providing enhanced aqueous humor outflow.

[0035] The stent 105 described herein can be formed from any of a variety of biologically derived materials having permeability and / or structure that allows water filtration through it. The stent 105 may be formed from biologically derived materials that are harvested, manipulated, cultivated, or otherwise manufactured. Biologically derived stent materials may be obtained or harvested from a patient or donor. Biologically derived stent materials may be harvested before or during surgery. Biologically derived stent materials may also be synthetic biological tissues created using in vitro techniques. Biologically derived materials may be stem cell-generated or biotechnically produced. Tissues may be generated by in-situ cell proliferation or non-cell proliferation. In exemplary embodiments, tissues may be 3D printed during manufacturing.

[0036] 3D printed tissue can be printed as a large patch of material to be cut during surgery, as described elsewhere in this specification. Alternatively, 3D printed tissue can be printed to have the dimensions of a final implantable stent. In this embodiment, the 3D printed material does not need to be trefined before implantation and can be implanted directly. For example, a 3D printed stent can be printed directly onto a cartridge configured to operatively connect with a delivery device described herein, which is then used to deploy the 3D printed stent into the eye. The 3D printed stent can be formed using the 3D printing process described in Biofabrication, 2019;11(3).

[0037] In exemplary embodiments, stent 105 is made of biological tissue. The biological material may be corneal tissue and / or non-corneal tissue. The biological material may include corneal tissue, scleral tissue, colloidal tissue, or cartilage tissue. In embodiments, the biological stent material may be degenerated corneal interstitial tissue lacking epithelium and endothelium, which is porous and hydrophilic permeable to allow aqueous filtration. The biological material of stent 105 may, but may not necessarily, be incorporated into the intrinsic anatomical structure of the eyeball after placement within the eyeball. The stent may be allowed to form pathways in the surrounding tissue that remain open for extended periods, even after stent absorption. The biological stent material may, if necessary, not be significantly absorbed or incorporated into the anatomy of the eye so that stent 105 remains implanted for extended periods or indefinitely.

[0038] In other embodiments, the stent 105 material may be made of a non-inflammatory complex carbohydrate or collagen. The stent 105 may also be formed from biodegradable or bioabsorbable materials including hydroxyaliphatic carboxylic acids such as polylactic acid, polyglycolic acid, and polyglycolic acid polylactic acid, as well as biodegradable polymers including homo or copolymers, polysaccharides such as ethylcellulose, crosslinked or uncrosslinked sodium carboxymethylcellulose, sodium carboxymethylcellulose starch, cellulose ether, cellulose acetate, cellulose phthalate acetate, hydroxypropyl methylcellulose phthalate, calcium alginate, acrylate polymers such as polypropylene, polybutyrate, polycarbonate, and polymethacrylate, polycaprolactones such as polyanhydride, polyvalerate, and poly-caprolactone, polydimethylsiloxane, polyamide, polyvinylpyrrolidone, polyvinyl alcohol phthalate, waxes such as paraffin wax and beeswax, natural oils, shellac, zein, or mixtures.

[0039] As mentioned above, biologically derived stent materials can be permeable or porous, allowing for aqueous filtration for adequate control or regulation of intraocular pressure. Permeable biological tissues described herein (e.g., sclera, cornea, collagen, etc.) are preferred stent materials, but any biological tissue, even if impermeable, is considered herein as a potential stent material that functions as a structural spacer to keep the annular dialysis open. Preferably, the stent material can form gaps that allow fluid to flow. The created gaps can run longitudinally along each side of the stent. If the stent material is permeable, more fluid can pass through the ciliary body dissection than if the stent material is impermeable and fluid is required to pass along the outside of the stent. Therefore, the materials considered herein do not need to be porous to provide the desired function, however, porosity of the material can enhance its function.

[0040] Generally, biologically derived stent materials have a certain degree of rigidity to maintain outflow from the anterior chamber, but are less rigid than conventional non-biologically derived polyimide shunts (e.g., Cypass, Alcon) used in the treatment of glaucoma. Stent materials can have sufficient structure to function as spacers to open a persistent ciliary superior outflow. Once implanted in annular dialysis, stent materials can maintain their structural height or thickness to allow fluid flow through or around the stent. Biologically derived stent materials have advantages over conventional non-biological materials such as polyimide in terms of biocompatibility, anatomical compatibility, and water permeability. Biologically derived stent materials can provide better fit and conformity to the scleral wall, and can reduce the likelihood of causing endothelial and scleral erosion / loss with time-dependent and chronic eye rubbing and blinking.

[0041] In one embodiment, the material used to form the stent is provided as an uncut patch of material configured to be manually loaded into the delivery device at the time of implantation. In another embodiment, the biological material used to form the stent is provided as an uncut patch pre-loaded into the shaft of the delivery device and held in the bone fenestration device 205 or cartridge. In yet another embodiment, the stent 105 is provided already cut into the shape of a stent, pre-loaded in the delivery device shaft 310 or in a cartridge configured to be loaded into the delivery device. The portion of the device carrying the biological stent material (whether pre-cut to stent size or cut as a larger patch size) may be packaged so that the material is stored in a medium or other suitable preservation solution for biological materials. In some embodiments, the entire device is packaged in a fluid bath or a portion of the device is submerged in a separate container before being attached to the bone fenestration device or delivery device at the surgical site.

[0042] After suitable material is obtained and pre-treated, an elongated stent of predetermined dimensions can be fabricated from a patch of material using a bone fenestration device. As will be discussed in more detail below, the bone fenestration can be performed during or before surgery. In certain embodiments, the stent may be formed by 3D printing and printed to the desired final dimensions for the stent, or printed as a patch of material to be bone-fenestrated during or before surgery. The bone fenestration achieved by the device described herein results in a very thin strip of material that can be implanted into the eyeball to provide regulation of water outflow. The achieved bone fenestration positions the cut implant within the conduit or lumen of the delivery device so that it can be subsequently delivered from the delivery device without the need to remove or transfer the cut implant from the cutting element to the delivery tube. The bone fenestration process allows the cut implant to be loaded into the delivery conduit for implantation into the eyeball, either simultaneously or in a subsequent operation.

[0043] As used herein, the term “material patch” means a piece of biologically derived material having a size along at least one dimension greater than the size of the stent cut from the material patch and implanted in a subject. In some embodiments, the material patch may have a generally square shape, and the stent trefined from the material patch may have a generally rectangular shape. For example, the material patch may be approximately 7 mm wide × 7 mm long × 0.55 mm thick, and the stent trefined from the material patch may be 0.3 to 0.6 mm wide × 7 mm long × 0.55 mm thick. The dimensions of the material patch and the trefined stent vary. The material patch and the trefined stent may each have the same length and thickness, but their widths may differ. The material patch and the stent trefined from the material patch may also have different lengths and thicknesses. For example, the material patch may have a first thickness, and the stent trefined from the material patch may have the same thickness, but when implanted, it may be folded or rolled to a different thickness than the material patch.

[0044] A stent trefined from a material patch may have width, length, and thickness. In embodiments, the width of a stent trefined from a material patch using the bone drilling window device described herein may range from at least 100 microns to about 1500 microns, or from 100 microns to 1200 microns, or from 100 microns to 900 microns, or from 300 microns to 600 microns. A stent trefined from a material patch may have a width of at least about 100 microns and a width of 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, 800 microns or less, 700 microns or less, 600 microns or less, 500 microns or less, 400 microns or less, 300 microns or less, or 200 microns or less. The length of a trefined stent trefined from a material patch may vary depending on the location of stent implantation. In some embodiments, the stent has a length between 1 mm and 10 mm, more preferably between 3 mm and 8 mm. The thickness of the stent cut from the material patch may range from 100 microns to about 800 microns, or from 150 microns to about 600 microns. In this embodiment, the biological material forming the stent may have a thickness of no less than 100 microns and no greater than 5 mm. The thickness of the stent also depends on whether the stent is folded or rolled during implantation; for example, a material patch with a thickness of 250 microns may be cut into a stent, and the stent may be folded during implantation to double its thickness to about 500 microns. The thickness of the stent also depends on the biological material used. For example, scleral tissue and corneal tissue often have a thickness of about 400 microns, but may shrink to about 250-300 microns after harvesting. Therefore, a stent cut from a shrunken patch of corneal tissue may have a thickness of only 250 microns. In some embodiments described in more detail below, the stent cut from a patch of material is cut to substantially fill the conduit through which it is to be delivered.

[0045] In non-limiting examples, a biological tissue stent has dimensions no less than 0.1 mm and greater than 8 mm in any direction, and a thickness no less than 50 microns and greater than 8 mm. In non-limiting examples, the stent is approximately 6 mm in length × 300-600 microns in width × 150-600 microns in thickness. The bone perforation opening can be no less than 1 mm and no greater than 8 mm in any direction. In non-limiting examples, the trephine-filled tissue has dimensions of 100-800 microns in width and 1 mm-10 mm in length. It should be understood that during the implantation procedure, multiple stents may be delivered to one or more target sites.

[0046] The trephining devices described herein provide accurate and precise cutting without wrinkles. The trephining devices can incorporate anterior-posterior capture, which fixes the material to be cut in the z-plane and prevents movement before the cutter engages the tissue. In the embodiments described in more detail below, the material to be cut is fixed, compressed, and / or tensioned before cutting.

[0047] Figures 2A and 2B show exemplary embodiments of a bone fenestration device 205. The intraoperative bone fenestration device used to form a stent can be combined with a delivery device such as an applier / injector for delivery to the implantation site, or it can be detachably coupled. Figures 3, 4, 13A, 13B, and 18A, 18B show embodiments of a bone fenestration device integrated with a delivery device. The bone fenestration device may also be a cartridge detachably coupled to the delivery device, as shown in Figures 5 and 6A, 6B. The cartridge containing a patch of material may be coupled to the distal portion of the delivery device, as shown in Figures 5 and 6A, 6B. In this embodiment, the cartridge can be removed from the delivery device before stent delivery to the eye. Alternatively, the cartridge containing a patch of material may be coupled to the proximal portion of the delivery device. In this embodiment, the cartridge does not need to be removed before stent delivery to the eye, and the stent, cut from the patch of material, may be deployed from the cartridge coupled to the delivery device without another step.

[0048] The bone fenestration device is configured to cut or otherwise form a biological tissue or patch of material having a first contour or shape (e.g., a wider, square sheet or patch of material) into a second contour or shape (e.g., a narrower, rectangular strip of material) that fits into an implantable stent having the dimensions described herein. Cutting performed using the bone fenestration device described herein may include guillotine, punch, rotation, slide, rolling, or pivot blade cutting operations. In some embodiments, the cutting is performed perpendicular to the plane of the patch of material. In some embodiments, the cutting is performed axially along the conduit of the implant. Thus, the axis of the bone fenestration device can be aligned with, within, or parallel to the conduit of the implant to allow for unimpeded loading and transport of tissue for implantation without manipulating, tearing, or damaging the fragile stent tissue. The bone drilling and fenestration process can precede the tissue fixation step, ensuring that the biologically derived tissue forming the stent is securely fixed between the two attachment planes so that the tissue does not wrinkle or deform and the subsequent bone drilling and fenestration cut is precisely sized. This fixation can optionally provide tension or stretch to the tissue within at least one plane, ensuring a clean cut of the tissue.

[0049] Bone drilling windows can be performed along or within a pathway or conduit formed within a structure, such as within a cartridge, within a delivery device, or within any other structure. Bone drilling windows in a patch of material can simultaneously or subsequently position the implant within a conduit (e.g., the lumen of the delivery shaft) so that the severed implant can be delivered to the eye through the conduit without the need to transfer it to another delivery device. In some embodiments, the cutting operation is from above the patch of material, and the sharp edge of the blade may cut the patch of material from the top surface of the patch. The cutter slides through the patch of material forming the implant so that the severed implant can be pushed down into the lumen of the delivery shaft along an axis perpendicular to the longitudinal axis A of the handle. In other embodiments, the cutting operation can be along the longitudinal axis A of the handle, sliding through the patch of material from the proximal end to the distal end of the handle 305. The cutting operation can be performed with the severed implant already properly positioned and / or aligned with the delivery conduit of the delivery shaft. The cutting member is movable relative to the handle, as is the recess that holds the patch of material in the cutting configuration. As the cutting member moves toward the cutting configuration, it can cut through the patch of material fixed within the recess forming the implant, and the cut implant can be aligned axially with the conduit for delivery.

[0050] A method for preparing an implant for implantation, and a method for inserting an implant into a patient's eye, may include inserting a patch of material into the proximal portion of an instrument. The instrument may include a cutting member and a distal portion sized for insertion into the eyeball. By cutting the patch with the cutting member, an implant can be formed. An implant that may have a longitudinal axis can be aligned with the longitudinal axis of the lumen of the cutting member from which the implant was cut once the cutting member has finished cutting the patch of material and forming the implant.

[0051] Next, the implant can be advanced from the proximal portion of the instrument to its deployment position within the lumen of the elongated tubular member of the distal portion of the instrument. The distal portion of the instrument is insertable into the anterior chamber of the eye so that it can be positioned adjacent to the ocular tissue as the implant is deployed from the instrument into the ocular tissue. For example, the distal portion of the instrument can be inserted into the anterior chamber from the inside through a corneal incision, while the proximal portion remains outside the eyeball. It should be understood that the distal portion of the instrument is useful for other delivery routes (e.g., transscleral delivery). Deployment of the implant into the ocular tissue may involve the implant being located at least partially between the ciliary body and the sclera of the eye. The implant can be located between the ciliary body and the sclera within an annular dialysis fissure.

[0052] The step of inserting a patch of material includes inserting the patch into a recess, such as the proximal portion of an instrument. The instrument may include a cover that closes over the recess containing the patch. The cover is fitted to engage with at least a portion of the patch of material before the patch is cut. The cover can prevent the patch from moving while the patch is being cut by the cutting member of the instrument. The cover (or some other element) may additionally impose tension on at least a portion of the patch before the cut is made. The tension may include acting an actuator to apply tension to a portion of the patch, but the tension does not necessarily have to involve a separate actuation and may be a result of closing the cover itself. The step of closing the cover over the recess may include engaging a portion of the cover with a first portion of the patch to compress a first portion of the patch and tensioning a second portion of the patch.

[0053] Preferably, the structure trefines the tissue in such a way that the tissue can slide, push, and / or pull along the conduit toward the implantation site in the eye. In other embodiments, the stent is fixed and held in place, and the conduit is withdrawn from the stent, leaving the stent implanted in the eyeball. The conduit may be incorporated into or coupled to a delivery device that implants and deploys the stent in the eyeball. The bone fenestration fenestration device may be made of any of a variety of materials, including rigid materials containing plastic and / or metal.

[0054] The bone fenestration device 205 shown in Figures 2A-2B may have an internal lumen or housing 210 of a size and shape that forms the elongated contour of the stent 105 when the tissue is placed inside the housing 210. The housing 210 has dimensions that approximate the size of the stent 105 to be formed to within a micron. The bone fenestration device 205 is configured to stabilize the tissue during the bone fenestration process. In this respect, the bone fenestration device 205 can fix the tissue in place and prevent the tissue from moving relative to the bone fenestration device 205 when the tissue is trefined. In this embodiment, the bone fenestration device 205 may have one or more wings 215 configured to articulate between an open configuration (Figure 2A) and a closed configuration (Figure 2B). When the bone fenestration device 205 is in the open configuration, a patch of material may be placed inside the housing 210. When the wing 215 is engaged in a closed configuration and the patch of material is in a predetermined position within the housing 210, one or more blades 220 may be positioned on the inner surface of the wing 215 so that the patch is cut into a stent of the desired dimensions.

[0055] The housing 210 of the bone fenestration device 205 can be and / or include a corresponding lumen of a delivery device 110 configured to advance or otherwise inject a stent 105 into the eyeball. In embodiments, the bone fenestration device 205 trefines or cuts tissue along a path that is aligned with or coaxial with the delivery path of the stent to the implantation site. For example, a stent cut from a patch of material held within the housing 210 may be guided distally to the delivery device shaft through a lumen extending through the anterior end 222 of the bone fenestration device 205. Thus, the stent can be first trefinated using a separate bone fenestration device. The bone fenestration device holding the trefinated stent can then be loaded into a delivery device designed to receive the bone fenestration device. This allows the stent to be loaded and deployed without removing it from the bone fenestration device for loading into the delivery device.

[0056] The bone perforation opening of the stent material is described in more detail below.

[0057] Referring again to Figure 1, the delivery device 110 is configured to be removably coupled to the stent 105 and is used to deliver the stent 105 from the inside via the delivery pathway to the implanted location. The delivery device 110 is schematically represented in Figure 1. Once coupled, the delivery device 110 is inserted into the eyeball and used to implant the stent 105 from the inside via the delivery pathway to the implanted location.

[0058] The delivery devices described herein can prepare an implant and perform internal insertion of the implant into the eyeball. Figure 3 is a perspective view of an exemplary embodiment of the delivery device 110 having integrated trephination. Figure 4 is a cross-sectional view of the delivery device 110 of Figure 3. The delivery device 110 may include a proximal handle 305 having a size and shape that can be grasped by one hand of a user. One or more actuators 315 can be positioned on the area of ​​the handle 305. The actuators 315 can be operated by one hand of a user, such as with a thumb or finger. The actuators 315 can be one or more knobs, buttons, sliders, or other interfaces configured to move one or more components of the delivery device 110, as will be described in more detail below.

[0059] An elongated shaft 310 (also referred to herein as the applicator or delivery body) extends distally outward from the handle 305. At least a portion of the shaft 310 contains or is coupled to the stent 105 for direct stent implantation. At least a portion of the shaft 310 extends along the longitudinal axis A, and the shaft 310 may be angled, curved, or flexible in the distal end region to form a distal curve or bend. In some embodiments, the shaft 310 may include flexible and rigid portions such that the shape of the shaft changes depending on the relative position of the portions. The shaft 310 may be curved at least along its length and / or be flexible.

[0060] The shaft 310 of the delivery device 110 is configured to be sized and shaped for internal delivery through a transparent corneal incision, allowing the stent 105 to pass through the distal end of the shaft 310 and remain inside the eyeball. In at least some embodiments, the distal end of the shaft 310 is sized to extend through an incision of about 1 mm in length. In another embodiment, the distal end of the shaft 310 is sized to extend through an incision of about 2.5 mm or less in length. In yet another embodiment, the distal end of the shaft 310 is sized to extend through an incision of 1.5 mm to 2.85 mm in length. In some embodiments, the maximum outer diameter of the shaft 310 does not exceed 1.3 mm. The most distal tip 316 of the shaft 310 can be blunt or sharp. The blunt distal tip 316 of the shaft 310 allows for dissection between tissues of the eye without penetrating or cutting tissue in order to position the stent 105. For example, the distal tip 316 of the shaft 310 may be configured to bluntly dissect the space between the ciliary body CB and the sclera S (e.g., the space above the ciliary body), while the stent 105 remains completely enclosed within the shaft 310 during the blunt dissection. In an alternative embodiment, the distal tip 316 of the shaft 310 has a sharp cutting configuration for dissecting, applying, and implanting into the subconjunctival space through the scleral wall. In yet another embodiment, the distal tip 316 may have a cutting configuration for dissecting and implanting within Schlemm's canal or transsclerolytically.

[0061] The stents described herein are formed as solid strips of material without a lumen. Thus, the stents are not deliverable on a guidewire, as many conventional glaucoma shunts are. Furthermore, the stents are formed from relatively soft tissue, which is more fragile than typical shunts formed from more rigid polymer or metallic materials. More rigid shunts can be implanted so that the distal end of the shunt is used to form a blunt dissection at the tissue interface into which the shunt is inserted. The stents described herein are preferably deployed using a retractable sleeve-type injector that, once in the correct anatomical position, allows the stent to be retracted while remaining loosely fitted and positioned. Furthermore, the stents described herein can be deployed in the eyeball by propelling the stent distally through at least a portion of the shaft 310. The stent may have dimensions that substantially fill the lumen of the shaft 310 (or the lumen of at least a portion of the shaft 310 into which it is delivered) so that the stent can be propelled distally through its portion without creasing or damage. The tolerance between the outer dimensions of the stent 105 and the inner dimensions of the conduit can be up to approximately 200%. The conduit may also be coated with a lubricating material (e.g., Teflon) to improve the advancement of the stent 105 through the conduit during deployment.

[0062] The shaft 310 can have an internally hollow shape for housing the stent 105. In some embodiments, the shaft 310 can be formed from an outer tube 318 (also referred herein as a tubular outer sheath) and an inner pusher 320 (also referred herein as an elongated member) positioned within the lumen of the outer tube 318 (see also Figures 4 and 7, and Figures 11C–11E). The movement of the outer tube 318 and / or the pusher 320 may act to deploy the stent 105 into the eyeball. The outer tube 318 and the pusher 320 of the shaft 310 may be operably coupled to one or more actuators 315 to deliver the stent 105 into the eyeball. The outer tube 318 may be fixed relative to the handle 305, and the pusher 320 may be movable relative to the handle 305. The outer tube 318 may be movable relative to the handle 305, and the pusher 320 may be fixed relative to the handle 305. Alternatively, both the outer tube 318 and the pusher 320 may be movable relative to the handle 305. The movement of the outer tube 318 and / or the pusher 320 can be generated using the same actuator 315 on the handle 305 or a different actuator 315, and can be actuated by the user moving the actuator 315 relative to the handle 305. The type of movement of the actuator 315 relative to the handle 305 can vary, including sliding or rotational movement. Embodiments shown in Figures 3 and 4 may include a shaft 310 having the outer tube 318 and the pusher 320. The outer tube 318 may be coupled to a slider, and the pusher 320 may be coupled to a knob 311 in the proximal region of the handle 305.

[0063] When the distal end of the shaft 310 reaches the desired position in the tissue, the stent 105 is left in place within the eyeball and the shaft 310 is withdrawn. In this embodiment, the outer tube 318 of the shaft 310 is retracted, for example, using an actuator 315 on the handle, while the pusher 320 remains stationary relative to the handle 305. Thus, the pusher 320 can act as a stopper, thereby preventing the stent 105 from following the outer tube 318 as it is retracted. As a result, the stent 105 is detached from the shaft 310 and left in the tissue.

[0064] The delivery device 110 may further include a cutting member 312 (see Figure 4), such as a blade or cutter tube, which moves relative to the handle 305 to cut tissue, thereby forming the stent 105. As described above, the stent 105 may be formed from a patch of material. The patch of material is loaded into the area of ​​the delivery device 110 and can be cut into a smaller stent shape upon delivery. The cutting member 312 can be operated by the user to create a stent from the patch of material.

[0065] In exemplary embodiments, the cutting member 312 is attached to a cover 314 that is movable relative to the handle 305 (see Figures 3 and 4). The cover 314 can be coupled to the distal end region of the handle 305 by a hinge 317 so that the cover 314 can rotate relative to the handle 305 around the pivot axis P of the hinge 317. The cover 314 can be lifted to pivot to an open configuration (see Figure 3) that exposes a recess 321 into which a patch of material 101 can be positioned and held fixedly relative to the handle. When the cover 314 is rotated around the pivot axis P back to the closed configuration, the patch of material 101 positioned in the recess 321 is compressed and / or pulled between the cover 314 and the handle 305. The compression and / or pulling of the patch of material 101 helps ensure a clean and complete cut of the material. In some embodiments, the patch of material 101 is placed under tension, such as outward stretching by the cover 314, before being cut by the cutting member 312. The patch of material 101 may be stretched outwards from the cutting position, as shown in Figures 15A-15C.

[0066] The recess 321 may be located within a proximal portion of the instrument, such as part of the handle 305. The recess 321 for holding the patch of material 101 may also be a recess in a cartridge that is removably coupled to a part of the instrument, such as within the area of ​​the handle 305 or coupled to the distal portion of the instrument.

[0067] It should be understood that pulling a patch may involve activating a separate actuator to pull the patch. Tensioning can also be achieved during the stabilization and compression processes without a separate actuator. For example, closing the cover 314 alone can result in both compression and tension of the patch of material without a separate actuator to tension the patch of material after compression.

[0068] The cover 314 can open along any of several or any orientation relative to the handle. For example, the pivot axis P of the hinge 317 may be substantially perpendicular to the longitudinal axis of the handle A. In this embodiment, the hinge 317 is positioned at the distal end of the handle 305 between the shaft and the cover 314 so that the cover 314 opens with a hinge by rotating upward and toward the shaft (see, for example, Figures 3 and 4). Alternatively, the hinge 317 may be positioned so that the cover 314 opens with a hinge by rotating upward toward the proximal end region of the handle 305 (see, for example, Figures 5 and 6A-6B). In yet another embodiment, the hinge 317 may be positioned on the side of the handle 305 so that the pivot axis P and the longitudinal axis A are substantially parallel to each other. In this embodiment, the cover 314 can swing outward away from the longitudinal axis A of the handle 305 (see, for example, Figures 15A-15C). Any of the various configurations are considered herein.

[0069] The cutting member 312 extends from the underside of the cover 314 and can cut a patch of material 101 (e.g., biological tissue) in a guillotine-like manner. Figure 4 shows the cover 314 in an open configuration, raised away from the recess 321 where the patch of material 101 is located. The cutting member 312 can extend from the underside of the cover 314 so that its cutting surface penetrates the patch of material 101. In some embodiments, the cutting member 312 is coupled to a movable actuator or push button 313 that can be actuated to move the cutting member 312 from the covering configuration to the cutting configuration. When the cover 314 is in a closed configuration, compressing and / or stretching the patch of material 101 between the underside of the cover 314 and the housing 305, the movable actuator 313 can be biased downward toward the cover 314 to position the cutting member 312 in the cutting configuration. The cutting member 312 can extend below the underside of the cover 314 and cut through the patch of material 101 held within the recess 321. One or more return springs 323 prompt the actuator 313 to return upward so that the cutting member 312 returns to the covering configuration. As the cutting member moves toward the cutting configuration, the cutting member 312 cuts a patch of material into the implant. Once cut, the implant also aligns axially with respect to the lumen of the shaft.

[0070] It should be understood that other types of cutting mechanisms can be used. For example, the descent of the cover 314 can also cut the patch of material 101 held in the recess 321 with a rotary cutting motion. In this embodiment, the cutting member 312 extends below the plane of the lower surface of the cover 314 so that the blade tip is available to cut the patch of material 101 when the cover 314 is rotated to a closed configuration. Alternatively, the cutting motion may be an axial cutting motion using a sliding cutting tube, in contrast to a cutting motion perpendicular to the plane of the patch of material 101, such that the bone perforation opening occurs along the graft conduit.

[0071] As described above, the cutting member moves toward the cutting configuration to cut the patch of material into the implant. Once cut, the implant axially aligns with the lumen of the shaft for deployment into the eyeball. Thus, the movement of the cutting member 312 cuts the stent and simultaneously positions the cut stent relative to the shaft 310 so that the stent can be delivered through the shaft 310. The cutting member 312 for cutting the patch of material 101 into a rectangular stent shape may include a pair of blades separated by a spacer. The spacer between the pair of blades engages with the cut stent 105 after cutting by the blades, and can bias the stent 105 downward through the slot of the outer tube 318. The pusher 320 can be configured to be fully retracted by the knob 311 so that the lumen of the outer tube 318 can freely receive the cut stent 105 through the slot. It should be understood that while the stent 105 is not specifically loaded into the lumen of the outer tube 318, it may be biased downward to a position relative to a delivery device that aligns the stent 105 with the implantation route. For example, loading of the outer tube 318 into the lumen may occur during additional steps such as the advancement of the stent 105 toward the lumen of the outer tube 318 following the cutting. Various sheath loading configurations, including top loading, front loading, rear loading, and side loading as described above, are considered herein, but these will be described in more detail below. Regardless of the configuration, the bone perforation window of the patch of material 101 can be positioned to allow the stent 105 to be deployed into the eyeball (i.e., aligned axially with the lumen of the shaft) without requiring manual tissue transfer of the fragments of the cut material.

[0072] Figure 5 shows another embodiment of the delivery device 110. This embodiment has a removable bone perforation window cartridge 205 near the tip of the delivery device 110. This embodiment reduces or minimizes the travel distance of the stent 105 once it is formed in the lumen of the shaft 310.

[0073] Similar to the earlier embodiments shown in Figures 3 and 4, the delivery device 110 may include a proximal handle 305 having one or more actuators 315, and a shaft 310 extending from the distal end region of the handle 305. The actuators 315 may include first and second sliders configured to move the outer sheath and the pusher of the shaft 310, respectively. It should be understood that the device 110 does not need to incorporate multiple actuators 315 to achieve motion of multiple components. For example, the device 110 may include a single actuator 315 configured to cut and deploy the stent 105 by causing motion of both the outer sheath and the pusher, for example, based on the degree of slider operation.

[0074] The bone drilling window cartridge 205 may include a base 324 and a cover 314 movably attached to the base 324. The cover 314 and base 324 may be joined together by a hinge 317 such that the cover 314 rotates around the pivot axis of the hinge 317. As in the previous embodiment, the cover 314 can be lifted and swiveled into an open configuration to expose a recess 321 in the base 324 where a patch of material can be positioned and secured. When the cover 314 rotates back into a closed configuration, the patch is compressed and / or tensed between the cover 314 and the base 324. The cover 314 and base 324 do not need to be hinged to each other. For example, the cover 314 and base 324 may be disengaged to simply expose the top surface of the base 324 so that the shaft 310 and the patch of material 101 can be properly positioned against the bone drilling window cartridge 205. The cover 314 may be configured to apply additional tension to the material patch 101, such as by extending outward from the center of the material patch 101 to improve the cut.

[0075] Figure 6A shows a delivery device 110 having a bone perforation window cartridge 205 coupled to the distal end region of a handle 305 in a closed configuration with the upper surface of the base 324 and the lower surface of the cover 314 of the bone perforation window cartridge 205 facing each other. Figure 6B is a cross-sectional view of the device 110 of Figure 6A, illustrating a shaft 310 extending through the handle 305.

[0076] The bone drilling window cartridge 205 may be provided pre-loaded with a patch of material positioned within the recess. For example, the patch of material can be compressed and / or tensioned within the base 324 and cover 314. The cutting member 312 can then be actuated to punch the stent 105 through the patch of material by, for example, pressing down a push button 313, prompting the cutting member 312 through the patch of material held within the bone drilling window cartridge 205. The delivery device 110 and the bone drilling window cartridge 205 can then be engaged with each other. For example, the shaft 310 can be inserted through the proximal port on the bone drilling window cartridge 205, thereby front-loading the cut stent 105 into the outer tube 318 for delivery to the eyeball. The cut stent 105 can then be fixed within the bone drilling window cartridge 205. In further embodiments, the stent can be loaded into the incision opening of the shaft from above the shaft, or by front-loading, or from behind the shaft.

[0077] It should be understood that the material patch does not need to be cut into the stent by the user at the time of implantation in the subject. The material patch may be cut into the stent well before implantation, for example, in a tissue bank or tissue engineering laboratory. The stent may be provided as a pre-cut and pre-loaded stent in a cartridge configured to bind with a delivery device. For example, a bone fenestration cartridge 205 may be provided to the user with a pre-loaded stent 105 pre-cut from a biological material patch. The cartridge 205 holding the stent 105 may be bound with the delivery device at the time of implantation. Once bound, the user can load the stent 105 into the shaft 310 of the delivery device as described elsewhere in this specification. In a further embodiment, the stent 105 may be provided to the user pre-loaded in the lumen of the shaft 310. The material patch may be provided in a cartridge or in the lumen of the shaft 310, appearing in a suitable tissue preservation medium, as is known in the art.

[0078] In this embodiment, the user can manually load patches of material 101 through opposing cutout windows 326 extending through the outer tube 318 of the shaft 310 of the delivery device 110 (see Figure 7). The cutout windows 326 of the outer tube 318 can extend through opposing side walls so that a patch of material 101 can be inserted through a first cutout window 326, traverse the lumen 328 of the outer tube 318, and be inserted through a second cutout window 326 on the opposite side of the lumen 328. The dimensions of the cutout windows 326 are sufficient to load patches of material 101 through the cutout windows 326, as shown in Figure 7. The patch of material 101 can have dimensions wider than the outer diameter of the outer tube 318 so that each side of the patch 101 extends beyond the side walls of the outer tube 318. Each cut-out window 326 within the outer tube 318 can have a length along the longitudinal axis A of the shaft 310 that is at least the same as the length of the material patch 101. The cut-out window 326 within the outer tube 318 can have a depth that is at least the same as the thickness of the material patch 101. Figure 8A is a schematic view of the cut-out window 326 of the shaft 310, seen from top to bottom. Figure 8B is a cross-sectional view of Figure 8A along line BB. The cut-out window 326, which can be created by removing the side wall on either side of the outer tube 318, forms a narrow web 330 on the top and bottom surfaces of the tube 318.

[0079] Figures 9A and 9B show another embodiment of a bone perforation window cartridge 205 having a cover 314 and a base 324. Figure 9A shows the base 324 with the upper cover 314 attached. Figure 9B is a cross-sectional view of the cartridge 205 showing a tissue patch 101 sandwiched between the base 324 and the cover 314. Figure 9C shows the base 324 of the bone perforation window cartridge 205 loaded with a patch of material 101, which is loaded into the cut-out window 326 of the tube 318 and positioned in a recess 321 of the base 324. The recess 321 may be positioned between a proximal slot 332 and a distal slot 334. The proximal slot 332 is sized to receive at least a portion of the outer tube 318 located proximal to the cut-out window 326, and the distal slot 334 is sized to receive a portion of the outer tube 318 located distal to the cut-out window 326. The recess 321 can have any of the following shapes, but is generally sized to receive a patch of material 101 loaded into the cutout window 326 of the outer tube 318. Thus, when the shaft 310 of the delivery device 110 is inserted into the bone perforation window cartridge 205, the shaft 310 is received in the proximal slot 332 and distal slot 334, and the tissue patch 101 is contained within the recess 321.

[0080] With respect to Figures 9A-9C, the cover 314 may have an upper surface that forms the outer surface of the cartridge 205. The cover 314 may also include a lower surface configured to engage with the upper surface of the cartridge base 324. The upper surface may include a recess 336 therein, which is an entrance to a hole 338 that extends from the upper surface through the entire thickness of the cover 314 to the lower surface. The upper surface of the cartridge base 324 includes an entrance to a hole 340 that extends through at least the thickness of the base 324. The hole 340 of the base 324 may, but does not have to, extend through the entire thickness of the base 324. When the cover 314 is in contact with the base 324, the holes 338, 340 are aligned to form a continuous channel. The continuous channel is sized and shaped to receive the cutting member 312, which will be described in more detail below. The cutting member 312 can translate relative to the cartridge 205 and extend from the top surface of the cover 314 through the entire thickness of the cover 314 into the hole 340 of the base 324.

[0081] The lower surface of the cover 314 surrounding the hole 338 and the upper surface of the base 324 surrounding the hole 340 can compress the patch of material 101 placed between them. The recess 321 of the base 324 may have a depth less than the thickness of the patch 101 placed within the recess 321 so that the patch of material 101 is compressed between the cover 314 and the base 324 when the cover 314 is joined to the base 324. The compression of the patch of material 101 between the base 324 and the cover 314 helps to prevent the patch of material 101 from moving during cutting by the cutting member 312. Tension can also be applied to the patch of material 101 before cutting. In some embodiments, the cover 314 is hinged to the base 324 (see Figure 5). The cover 314 and the base 324 can be reversibly secured to each other so as to latch or otherwise reversibly connect to prevent the cover 314 from unintentionally opening relative to the base 324 when the cover 314 is closed onto the base 324.

[0082] Figure 10A illustrates a bone perforation window cartridge 205 in a closed configuration with the base 324 and cover 314. Figure 10B is a cross-sectional view of the bone perforation window cartridge 205 in a closed configuration, with a patch of material 101 sandwiched between the cover 314 and the base 324 and the cutting member 312 inserted into the hole 338 in the cover 314. Figure 10C is a cross-sectional view of the bone perforation window cartridge 205 with the cutting member 312 fully inserted through the cover 314 into the hole 340 in the base 324.

[0083] The cutting member 312 may include a pair of blades 344 and an enlarged grip feature or handle 343. The handle 343 is positioned at the upper end of the blade housing 342, while the pair of blades 344 protrude from the lower end of the blade housing 342. The handle 343 can be shaped and sized to allow the user to comfortably grip the cutting member 312. Figures 10A–10C illustrate the handle 343 having a disc shape configured to be received in a correspondingly shaped recess 336 on the upper surface of the cover 314. Various shapes are considered herein.

[0084] The blade housing 342 may include a central channel 346 into which the upper part of the blade 344 is received. The lower cutting surface of the blade 344 extends below the blade housing 342. A pair of blades 344 may be separated from each other by a spacer 345 that defines a gap between the blades 344. The size of the gap is selected based on the desired width of the stent 105, which is achieved when the blades 344 cut through a patch of tissue 101.

[0085] The cutting member 312 can be received in a recess 336 within the cover 314, such that the blade 344 extending from the lower end of the cutting member 312 is first inserted into the hole 338 in the cover 314, followed by the blade housing 342 (see Figure 10A). Therefore, the hole 338 in the cover 314 can be sized and shaped to receive not only the blade 344 but also at least a portion of the blade housing 342. The handle 343 can be sized and shaped to be received in the recess 336 of the cover when the cutting member 312 is fully inserted into the cartridge 205.

[0086] The tissue patch held within the cutting area of ​​the shaft is cut at two locations, creating a thin strip of material (i.e., stent 105) from the patch of material 101. As the cutting member 312 is further advanced through the hole 338 in the cover 314, the blade 344 is advanced toward the patch of material 101 compressed between the cover 314 and the base 324 (see Figure 10B). As the cutter is further advanced through the hole 338 in the cover 314 and enters the hole 340 in the base 324, the blade 344 cuts through the patch of tissue 101 located in the recess 321 (see Figure 10C). The blade 344 makes two cuts in the patch of material 101 so as to extend downward through the hole 340 in the base 324, completely cutting open the patch 101 to form the stent 105. The movement of the cutter toward the cutting configuration cuts a patch of material into a stent as the cutting member moves toward the cutting configuration, and once cut, the stent aligns axially with the lumen 328 of the outer tube 318. The formed stent 105 is thus already loaded into or within the lumen 328 of the outer tube 318, so that no loading process is required.

[0087] The blade 344 is inserted through a continuous channel formed by holes 338, 340 in the cover 314 and base 324. The housing 342 can seat in hole 338, and / or the handle 343 can seat in recess 336 in cover 314, thereby preventing any further downward movement of the blade 344. The formed stent 105 is held tightly within the lumen 328 of the outer tube 318. As described above, the outer tube 318 of the delivery device shaft 310 may include a pair of cut-out windows 326 in the opposing side walls that form a narrow web 330 on the upper and lower surfaces of the tube 318. As best shown in Figures 11A-11E, each of the blades 344 is received within the respective cut-out window 326 of the tube 318 when the cutting member 312 is inserted into the cartridge 205 so that the blade 344 extends into hole 340 in the base 324. The gap between the pair of blades 344 is sized to accommodate and receive the web 330 as the blades 344 slide over the shaft 318 located within the cartridge 205. Once cut, the stent 105 is housed within the lumen 328 of the outer tube 318 at the location of the cut-out window 326, with one blade 344 surrounding the stent 105 on the first side and the second blade 344 surrounding the stent 105 on the second opposite side. This enclosure forms a path for the stent 105 to unfold from the lumen 328 out of the distal end of the shaft 310, which will be described in more detail below.

[0088] In Figures 11A to 11E, the blade 344 may include a single beveled edge angled to propagate the cut, similar to scissors. It is preferable that the blade 344 does not cut the tissue. The blade 344 is positioned relative to the cartridge 205 so that a complete cut occurs through the patch 101 when the cutting member 312 moves completely through the cartridge 205.

[0089] Once the cutting member 312 has moved completely into the cover 314 (i.e., the cutting member 312 is positioned in the cutting configuration), the blade housing 342 is constrained within the hole 338 of the cover 314. Therefore, the length of the blade housing 342 is not longer than the depth of the hole 338 in the cover 314, and preferably slightly shorter. In some embodiments, and as best shown in Figure 10B, the distal exit from the hole 338 on the lower surface of the cover 314 may have dimensions smaller than the entrance to the hole 338. If the entrance to the hole 338 is sized to accommodate the blade housing 342, the exit from the hole 338 may be sized to accommodate only the blade 344 and not the blade housing 342. This arrangement prevents over-insertion of the cutting member 312 into the cartridge 205, in that the lower end region of the hole 338 acts as a stop for the blade housing 342.

[0090] The cutting member 312 may additionally include a safety sheath (not shown) configured to surround the dual blades 344 extending from the lower end of the blade housing 342. The safety sheath can prevent accidental damage to the blades 344 or the user when the cutting member 312 is not engaged with the cartridge 205. For example, the safety sheath may surround all of the blades 344 except the lower end of the cutting member 312. The cover 314 and base 324 of the cartridge 205 may include additional channels that are aligned, sized, and shaped to receive the safety sheath surrounding the blades 344 when the cutting member 312 is inserted into the cartridge 205.

[0091] Figure 11E is a cross-sectional view of the cut-out window 326 of the outer tube 318, with blades 344 positioned on both sides of the upper and lower webs 330. As previously mentioned, the shaft 310 of the delivery device 110 may include a pusher 320 positioned within the lumen 328 of the outer tube 318. At least a portion of the pusher 320 may have a cross-sectional shape configured to slide over the blades 344 positioned within the cut-out window 326 of the tube 318. The cross-sectional shape of at least a portion of the pusher 320 may incorporate a flat side configured to align with the cut-out window 326 as the pusher 320 extends relative to the outer tube 318 during the deployment of the stent 105 from the lumen 328. The flat side of the pusher 320 (opposite the convex side) may define a width of size for sliding between the two blades 344 positioned within the cut-out window 326. Similar to a stent, at least a portion of the pusher 320 can be sized to completely fill at least a portion of the lumen 328 of the outer tube 318. The outer tube 318 may be a hypotube not exceeding approximately 18G (0.050 inch OD, 0.033 inch ID), 20G (0.036 inch OD, 0.023 inch ID), 21G (0.032 inch OD, 0.020 inch ID), 22G (0.028 inch OD, 0.016 inch ID), 23G (0.025 inch OD, 0.013 inch ID), 25G (0.020 inch OD, 0.010 inch ID), 27G (0.016 inch OD, 0.008 inch ID), 30G (0.012 inch OD, 0.006 inch ID), or 32G (0.009 inch OD, 0.004 inch ID). In some embodiments, the outer tube 318 is a hypotube with an inner diameter ranging from less than approximately 0.036 inches to approximately 0.009 inches. The dimensions of the outer tube 318 can be selected based on the desired dimensions of the stent to be implanted, as discussed in more detail above.

[0092] While the shaft 310 of the delivery device 110 is positioned within the cartridge 205 and the blade 344 is still in the cutting configuration, the pusher 320 can be pushed distally from the handle 305 of the delivery device 110 to position the stent 105, cut from the patch of material 101, in a ready position within the lumen 328. In some embodiments, the pusher 320 can be advanced distally relative to the handle 305, for example, using an actuator 315 on the handle 305. The presence of the blades 344 on both sides of the cut-out window 326 and the upper and lower webs 330 prevents the stent 105 from buckling within the lumen 328 during this preparation process. The conduit in which the stent 105 is held is sized to match the external dimensions of the stent being implanted, thereby preventing buckling and wrinkling as the stent 105 is pushed into the ready position.

[0093] When the stent 105 is advanced into the distal tip region of the outer tube 318, the blade 344 can be retracted from the base 324. In some embodiments, the cutting member 312 can be removed from the cartridge 205, and the cover 314 opens relative to the base 324, so that the shaft 310 of the delivery device 110 can be removed from the cartridge 205. In other embodiments, the cutting member 312 can be withdrawn from the base 324, but remains engaged with the cartridge 205 for the shaft 310 of the delivery device 110 to be withdrawn from the cartridge 205. The shaft 310 can be withdrawn from the cartridge 205, whether the cover 314 is open or closed. Once the delivery device 110 and the cartridge 205 are disengaged from each other, the delivery device 110 is ready for use in inserting the stent 105 into the eyeball, which will be described in more detail below.

[0094] As described above, movement of the components of the delivery device 110 can be achieved using one or more actuators 315 of the handle 305. Figure 6B is a cross-sectional view of an embodiment of the delivery device 110 having its distal shaft 310 engaged with a bone perforation window cartridge 205. The shaft 310 may include a pusher 320 and an outer tube 318. The pusher 320 may be coupled to a first actuator 315, and the outer tube 318 may be coupled to a second actuator 315. Each of the first and second actuators 315 may be a slider configured to advance and retract its respective component. The first actuator 315 can be pulled out proximal so that the pusher 320 is in the closest position to the outer tube 318 during cutting of a patch of material 101 compressed and / or tensioned within the cartridge 205. Once the patch of material 101 is cut, the user can advance the first actuator 315 to push the pusher 320 distally, preparing the stent 105 in the lumen 328 of the outer tube 318 toward the distal end of the shaft 310. After the cut stent 105 is prepared in its distal position in the lumen 328, the cartridge 205 can be detached from the shaft 310. The outer tube 318 of the delivery device 110 may be used to dissect the tissue of the eye until it reaches the target position. At the position where the delivery device deploys the stent 105 into the eyeball, the first actuator 315 coupled to the pusher 320 is maintained in this distal position, and the second actuator 315 may be pulled out to retract the outer tube 318. This relative movement of the outer tube 318 relative to the pusher 320 causes the stent 105 to be deployed from the lumen 328 anatomically (as shown in Figure 12B). It should be understood that the additional distal movement of pusher 320 is used to assist in the deployment of stent 105 from lumen 328.It should also be understood that the forward movement of the pusher 320 and the retraction of the outer tube 318 are controlled by the dual actuator 315 as described above, or by a single actuator 315 capable of moving both the pusher and the outer sheath depending on the degree of operation. Furthermore, the shaft 310 of the delivery device 110 can be used to inject viscoelastic material during treatment, using the pusher 320 as a plunger.

[0095] Figures 13A, 13B and 18A, 18B show related embodiments of the delivery device 1110 having an integrated trefin that forms a system for preparing the implant and performing internal insertion of the implant into the eyeball. As described elsewhere in this specification, the delivery device 1110 may be used to insert into the eyeball and implant the stent 105 at the implanted location via an internal delivery pathway. The delivery device 1110 may include a proximal portion, such as a proximal handle 1305, which is sized and shaped to be grasped by the user and remains outside the patient's eye. The delivery device 1110 may also include a distal portion. The distal portion may include an elongated delivery shaft 1310 extending distally from the proximal handle 1305. The elongated delivery shaft 1310 includes an outer tube 1318 having a lumen 1328 (see Figure 14A). An axially movable cutter tube 1312 may be positioned within the handle 1305. The pusher 1320 is shown positioned within the lumen 1378 of the cutter tube 1312. The pusher 1320 is configured to advance distally through the lumen 1328 of the outer tube 1318. Where a delivery device is described herein as suitable for insertion from inside the implant, it should be understood that other approaches for implantation should also be considered. For example, the delivery device may be used to perform a transscleral approach for implant delivery.

[0096] With respect to Figure 14A, the delivery device 1110 may include an access door 1314 coupled to the area of ​​the handle 1305 by a hinge 1317, etc., so that the door 1314 can rotate around the pivot axis of the hinge 1317 relative to the handle 1305. When the access door 1314 is in an open configuration, the recess 1321 is exposed. A patch of material 101 may be loaded into the recess 1321 for cutting into the stent 105 prior to delivery. A pusher 1320 positioned within the lumen 1378 of the cutter tube 1312 is retracted proximal to the recess 1321 so that the patch of material 101 can be positioned in the recess 1321. Figure 14B shows the access door 1314 rotated to a closed configuration that captures the patch of material 101 in the recess 1321. In some embodiments, the access door 1314 may be formed of a transparent or translucent material so that a patch of material 101 placed in the recess 1321 can be visualized by the user after loading (see Figure 18A). The access door 1314 may also include one or more latches 1322 (see Figure 19A) to ensure that once the door 1314 is closed, it remains closed until the user wishes to open the door 1314 again. In some embodiments, the latches of the access door 1314 may include interference mating features, magnets, or other elements.

[0097] The recess may be located within a part of the instrument, such as within the handle as described above. Alternatively, the recess may be in a cartridge detachably coupled to the instrument. The cartridge may be coupled to the distal part of the instrument and can be removed before deployment into the eyeball, as shown herein. The cartridge may also be coupled to the proximal part of the instrument and may or may not be removed before deployment.

[0098] As the door 1314 rotates around the pivot axis P from an open configuration to a closed configuration, the patch of material 101 positioned within the recess 1321 is captured, compressed, and / or pulled. The door 1314 can be adapted to engage at least a portion of the patch of material before it is cut. The door 1314 can prevent the patch from moving during cutting by the cutter.

[0099] In some embodiments, at least a portion of the recess 1321, for example, the portion aligned with the centerline of the transplant conduit, may have a depth less than the thickness of the patch 101 of material held within the recess 1321. When the door 1314 is closed, the patch of material 101 is slightly compressed.

[0100] At least a portion of the patch of material 101 can be placed under tension before cutting. Placing the patch of material 101 under slight tension before cutting improves the cutting achieved by the cutter tube 1312. The tensioning of the patch portion includes compressing the first and second portions of the patch and pulling the central portion of the patch, which is located between the first and second portions. The central portion of the patch becomes the implant when the patch is cut by the cutter tube 1312.

[0101] The process of tensioning a portion of the patch may include operating an actuator to tension a portion of the patch. Operating the actuator may include rotating the actuator to tension a portion of the patch. For example, a cover may include an actuator, and the operation of the actuator may be able to tension at least a portion of the patch. However, applying tension does not have to be a separate operation. As discussed elsewhere in this specification, both fixation and tension can be provided to the patch by closing the access door 1314. Figures 15A–15C are schematic cross-sectional views of the handle 1305 showing the access door 1314 and a patch of material 101 placed in a recess 1321. The door 1314 may include features configured to apply a small amount of tension or stretch to the patch of material 101 in order to improve cutting. The door 1314 may be coupled to a stretcher 1350 having a pair of flexible stretcher legs 1352. The stretcher legs 1352 extend into the recess 1312 until each of the legs 1354 at the end of the legs 1352 contacts a patch of material 101 (see Figure 15B). One leg 1354 can contact a first portion of the patch of material 101 on a first side of the centerline, and the opposite leg 1354 can contact a second portion of the patch of material 101 on a second opposite side of the centerline. The stretcher 1350 can be operated from a first position in which the stretcher 1350 is raised relative to the recess 1321. When the stretcher 1350 is biased downward, the stretcher legs flex, and the legs 1354 are biased further outward from the centerline and move away from each other (see arrows in Figure 15C). The distance between the legs 1354 is sufficient to allow the cutter tube to slide axially through the recess 1321 between the legs 1354 to cut the patch of material 101. The underside of the leg 1354 may have surface features 1355, such as ridges, bumps, or other textures, that optimize the interface between the leg 1354 and the patch of material 101. The surface features 1355 allow the leg 1354 to stretch the patch of material 101 outward as the leg 1355 is pushed outward.

[0102] The stretcher 1350 can have any of the following configurations. The stretcher 1350 may be a button, as shown in Figures 13A-13B and 15A-15C. The stretcher 1350 may be a dial, as shown in Figures 18A-18B, 19A-19B, 20A-20C, 21 and 22. Various other actuators configured to apply tension to patch 101 are conceivable. In embodiments where the stretcher 1350 is a button, the door 1314 may optionally incorporate an additional stretch release button 1357 (see Figure 13A) to release the applied tension.

[0103] Regardless of the configuration, the stretcher 1350 may have an upper end region 1360 and a lower end region 1362 (see Figure 20A). The upper end region 1360 is configured to be gripped and actuated (i.e., pushed or rotated). The lower end region 1362 of the stretcher 1350 can engage with the access door 1314. Figure 21 shows a dial-type embodiment of the stretcher 1350 having a thread 1367 in the lower end region 1362 of the stretcher 1350 that engages with a corresponding thread 1365 in a hole 1364 on the upper surface of the door 1314. Rotation of the stretcher 1350 relative to the hole 1364 further pulls the stretcher 1350 into the hole 1364 and pushes the legs 1354 further into the recess 1312.

[0104] As discussed elsewhere in this specification, the step of pulling the patch may include the step of operating an actuator, such as a dial, to pull the patch. Tensioning can also be achieved without separate operation. For example, by closing the door 1314, both fixing and tensioning of the patch of material can be achieved without a separate actuator for applying tension to the patch of material after compression. Thus, the door 1314 can achieve a pre-fixed tension in the patch of material when closed without separately operating the stretcher 1350 up and down relative to the material.

[0105] The recess 1321 receives a patch of material 101. The recess 1321 may include an inverted V-shaped projection 1371 that guides the centerline of the patch of material 101 upward toward the door 1314, while allowing the patch of material 101 to hang downward into the corresponding channels 1370 on either side of the centerline (see Figures 19A and 21). When the door 1314 is closed, the stretcher leg 1352 extends into the recess 1312 until each of the legs 1354 of the stretcher leg 1352 contacts the side of the patch of material 101 hanging into the channel 1370 (see Figure 21). One leg 1354 may contact a first portion of the patch of material 101 in the first channel 1370 adjacent to the centerline, and the opposite leg 1354 may contact a second portion of the patch of material 101 in the second channel 1370 on the opposite side of the centerline. As the stretcher 1350 is further drawn into the hole 1364 by turning a dial or the like, the legs 1354 push these parts deeper into their respective channels 1370, thereby pressing the centerline of the material patch 101 against the inverted V 1371 (see Figure 21) of the recess 1321. The distance between the legs 1354 is sufficient for the cutter tube 1312 to pass between them. The inverted V 1371 may include a shallow central channel 1372 of a size and shape that receives the shape of the lower wall of the cutter tube 1312 when the cutter tube 1312 is advanced distally to cut the patch of material 101.

[0106] The cutting member may include a lumen, a distal opening, and a pair of opposing cutting blades. The cutting process may include advancing the cutting member to cut a patch of material and capturing the implant within the lumen of the cutting member. The pair of opposing cutting edges may cut the patch in two places, separating the implant from the rest of the patch of material. The distal portion of the cutting member may be chamfered. The longitudinal axis of the implant may remain aligned with the longitudinal axis of the lumen of the cutting member when the cutting member has finished cutting the patch and forming the implant.

[0107] The cutter tube 1312 can be a double-beveled hypo tube forming two leading points 1372 (see Figures 23A-23D). The two leading points 1372 can be positioned above and below the patch of material 101, respectively, as the cutter tube 1312 is advanced into the cutting configuration and slicing through the patch of material 101. The lower leading point 1372 may be received within a shallow central channel 1372 of an inverted V-shape 1371, while the upper leading point 1372 slides over the patch of material 101. The leading points 1372 can be blunt or sharp. The cutting surface of the cutter tube 1312 includes the inner edges 1374 of each bevel 1376. The inner edges 1374 are separated from each other by the lumen 1378 of the cutter tube 1312 so that the cutter tube 1312 slices the patch of material 101 in two places. Therefore, the inner diameter of the cutter tube 1312 or the distance between the inner edges 1374 determines the width of the stent 105 to be cut.

[0108] Once severed, the stent 105 is housed within the lumen 1378 of the cutter tube 1312, which forms a housing for the stent 105. The stent 105 may have dimensions that substantially fill the lumen 1378 of the cutter tube 1312. The axial movement of the cutter tube 1312 distally toward the severed configuration positions the cutter tube 1312 such that its walls bridge the recess 1321 and form part of the implantation conduit 1319. The lumen 1378 of the cutter tube 1312 can be coaxial (e.g., continuous or discontinuous) with the lumen of the elongated shaft 1310 through which the stent 105 will be delivered to the eye. For example, as shown in Figure 17B, the severed stent 105 can be advanced along the implantation conduit 1319 from the cutter tube 1312 toward the distal end of the delivery shaft 1310. Therefore, the axial movement of the cutter tube 1312 along the axis of the implantation conduit 1319 simultaneously cuts the stent from the patch of material 101 and axially aligns the cut stent with or relative to the lumen of the delivery shaft so that the stent 105 can be deployed in the eye without any tissue migration process.

[0109] The inner elongated member or pusher 1320 is movable relative to the lumen of the delivery shaft. The stent 105 is pushed distally out of the cutter tube 1312 by the pusher 1320. As described above, the elongated shaft 1310 of the delivery device 1110 may include an outer tube 1318 and an inner pusher 1320 positioned within the lumen of the outer tube 1318. The pusher 1320 is sized and shaped to move distally through the lumen 1378 of the cutter tube 1312, urging the stent 105 toward the distal end of the outer tube 1318 (see Figure 17B). In some embodiments, the outer tube 1318 is fixed to the handle 1305, and the inner pusher 1320 is movable relative to the outer tube 1318 to deploy the stent 105 from the outer tube 1318. In other embodiments, both the outer tube 1318 and the pusher 1320 are movable relative to the handle 1305 and relative to each other. The distal end of the pusher 1320 may be shaped to bias the stent 105 distally without damaging it.

[0110] In further embodiments, the elongated delivery shaft 1310 may include a fixed outer tube 1318 and an introduction tube 1380 positioned and movable through the lumen 1328 of the outer tube 1318 (see Figures 18A-18B). The pusher 1320 is, in turn, movable through the lumen 1382 of the introduction tube 1380. The distal end region of the elongated tubular member for delivering the implant into the eyeball may be angled, curved, and / or flexible. In some embodiments, the introduction tube 1380 may have a curved shape in its distal end region, and / or the introduction tube 1380 may be flexible to conform to the curved shape. The curved shape of the distal end region of the introduction tube 1380 may conform to the shape of a desired implantation site, such as the curvature of the eye near the anterior horn. The outer tube 1318 may be a rigid tube, and the introduction tube 1380 may be flexible. The pusher 1320 can be a shape-set nitinol that, when retracted proximal, takes on the shape of the rigid outer tube 1318, and when extended distally beyond the distal opening of the outer tube 1318, relaxes to return to its shape-set configuration (i.e., having a curve or bend away from the longitudinal axis of the outer tube 1318). The introduction tube 1380 is flexible enough to take on the shape of the pusher 1320 when the pusher 1320 extends beyond the outer tube 1318. Thus, the introduction tube 1380 can be more flexible than the pusher 1320, and the pusher 1320 can be more flexible than the outer tube 1318. In some embodiments, the introduction tube 1380 can be formed from silicone, thermoplastic elastomer, polyethylene, polypropylene, or a combination thereof. The introduction tube 1380 can have some degree of rigidity, but not so rigid that it cannot retract onto the pusher 1320 during deployment.

[0111] The introduction tube 1380 and pusher 1320 can cooperate to deploy the stent 105 into the eyeball after the stent 105 has been cut by the cutter tube 1312. The pusher 1320 can guide the stent 105 from the lumen 1378 of the cutter tube 1312 into the lumen 1382 of the introduction tube 1380. Figure 24A shows the introduction tube 1380 extending through the lumen 1378 of the cutter tube 1312 and beyond the distal end of the outer tube 1318. The stent 105 is positioned within the lumen 1382 of the introduction tube 1380, biased distally by the pusher 1320, which is also positioned within the lumen 1382 of the introduction tube 1380. The stent 105 is biased distally within the lumen 1382 by the pusher 1320 until it is positioned within the distal end region of the injector tube 1380 (Figure 24B). At this stage of deployment, the pusher 1320 advances beyond the distal end of the rigid outer tube 1318 so that the pusher 1320 can relax and return to its curved or bent shape. The injector tube 1380, being more flexible than the pusher 1320, takes the shape of the pusher 1320. The severed stent 105, in this ready position near the distal end of the injector tube 1380, is ready to be implanted into the eyeball. With the pusher 1320 stationary, the injector tube 1380 can be retracted to effectively push the stent 105 out of the lumen of the injector tube 1380 (see Figure 24C).

[0112] The step of advancing the implant from the proximal portion of the instrument may include pushing the implant from the lumen of the cutting member into the lumen of the elongated tubular member of the distal portion. The distal portion of the instrument may be positioned adjacent to ocular tissue to place the implant within the eyeball, for example, between the ciliary body and the sclera, while the implant remains at least partially within the lumen of the distal portion of the instrument. The stent 105 may be deployed from the instrument when the introduction tube 1380 is retracted from the implant, while maintaining the position of the implant relative to adjacent ocular tissue. The method of implantation and delivery of the stent 105 is described in more detail below.

[0113] The movement of the cutting and deployment components (e.g., one or more of the cutter tube 1312, pusher 1320, introduction tube 1380, and outer tube 1318, if present) can be achieved by one or more actuators 1315 positioned on one or more regions of the handle 1305. In some embodiments, one or more actuators 1315 for a first function of the delivery device 1110 may be positioned on a first region of the handle 1305, and one or more actuators 1315 for a second function of the delivery device 1110 may be positioned on a second region of the handle 1305. The first plurality of actuators 1315 may be positioned on the first region of the handle 1305 to prepare a patch 101 of material into the stent, and the second plurality of actuators 1315 may be positioned on the second region of the handle 1305 to deploy the stent 105 cut from the patch 101. For example, the upper region of the handle 1305 may include a first actuator 1315 for capturing and / or extending a patch of material 101, a second actuator 1315 for moving a cutter tube 1312 to cut the patch of material 101, and a third actuator 1315 for moving a pusher 1320 to position the cut stent 105 ready for deployment from the device 1110. The bottom region of the handle 1305 may include a fourth actuator 1315 for deploying the stent 105 into the eyeball.

[0114] Figure 13A shows a top view of an embodiment of the delivery device 1110, and Figure 13B shows a bottom view of the device 1110. The upper region of the handle 1305 may include a first actuator 1315, which is a stretcher 1350 for capturing and stretching a patch of material 101 in the recess, and another actuator 1315, which is a slider for moving the cutter tube 1312. The bottom region of the handle 1305 may include an actuator 1315, which is a slider for moving a pusher 1320 to push the stent 105 out of the outer tube 1318.

[0115] Figure 18A shows a top view of an embodiment of the delivery device 1110, and Figure 18B shows a bottom view of the device 1110. The upper region of the handle 1305 may include a first actuator 1315 which is a stretcher 1350 for capturing and stretching a patch of material 101 in the recess, a second actuator 1315 which is a slider for moving the cutter tube 1312, and a third actuator 1315 which is a wheel for gradually advancing the pusher 1320. The bottom region of the handle 1305 may include a fourth actuator 1315 which is a spring retraction button for retracting the introducer tube 1380 to release the stent 105 from the shaft 1310.

[0116] The configuration of actuator 1315 may vary. For example, actuator 1315 may include any of the following: various sliders, dials, buttons, knobs, or other types of actuators.

[0117] In embodiments, one or more actuators 1315 configured to move one or more components of the apparatus in the axial direction may include a scroll wheel 1385 (see Figure 25). The scroll wheel 1385 may be connected to a pinion gear 1387 that engages with a corresponding rack gear 1389. The rotation of the pinion gear 1387 moves the rack gear 1389 in the axial direction, allowing one of the axially movable components, such as a pusher 1320 or a cutter tube 1312, to advance or retract. Figure 25 shows the rack gear 1389 mounted on a pusher 1320. The scroll wheel 1385 can provide more progressive and precise movement of the components. A scroll wheel advance mechanism is described in US10,154,924 and is incorporated herein by reference.

[0118] In another embodiment, one or more actuators 1315 configured to move one or more components of the device axially may include a spring-loaded push button 1390. The introducer tube 1380 may be biased distally in an extended state relative to the handle 1305, thereby compressing the front spring 1392 (see Figure 26). The push button 1390 can be held in a forward-locked position by a latch 1394 so that the spring 1392 remains compressed during the advancement of the stent 105 to a target position in the eyeball. Applying a downward force to the push button 1390 releases the latch 1394, causing the spring 1392 to push the introducer tube 1380 proximal, thereby retracting the introducer tube 1380. The contraction of the introducer tube 1380 relative to the pusher 1320 can act to release the implant 105 in the eyeball. A spring-loaded retraction mechanism is described in US9,241,832 and is incorporated herein by reference.

[0119] Activating the first actuator can tension at least a portion of the patch before cutting; activating the second actuator can advance the cutting member to cut the patch after tensioning; activating the third actuator can advance the implant to the deployed position; and activating the fourth actuator can deploy the implant from the instrument. Each actuator can be operationally coupled to the instrument. It should also be understood that one or more steps in cutting and / or deploying the implant from the instrument can be combined. For example, the first actuator can fix, compress, and tension a portion of the patch before cutting; the second actuator can advance the cutting member and advance the cut implant to the deployed position; and then the third actuator can deploy the implant from the intraocular instrument. The step of advancing the implant from the proximal portion of the instrument may include pushing the implant from the lumen of the cutting member into the lumen of the elongated tubular member of the distal portion.

[0120] The advancement of the cutter tube 1312 allows the stent 105 to be cut from a patch of material and positioned within the lumen of the cutter tube 1312. The inner diameter of the cutter tube 1312 can be substantially the same as the inner diameter of the outer introduction tube 1380. The pusher 1320 is biased distally through the lumen of the cutter tube 1312, allowing the cut stent 105 within the lumen to be biased into the lumen of the introduction tube 1380. However, since the inner dimensions of the cutter tube 1312 and the introduction tube 1380 may be substantially the same, if the introduction tube 1380 is biased proximal by the spring, the cutter tube 1312 is biased posteriorly by the introduction tube 1380. The stent 105 is substantially housed within the implantation conduit and can be advanced line-to-line within the instrument as it is advanced distally. Once the stent 105 is cut from the material patch, the implantation route for the stent 105 may include the lumen of the cutter tube 1312, the lumen of the injector tube 1380, and any other conduits between them, so that the stent does not need to move between “gaps” or “edges” within the implantation conduit during its transport within the conduit. The implantation conduit provides a smooth path for the deployment of the stent 105 through the instrument.

[0121] Tissue bone fenestration and tissue loading using a delivery device can be performed simultaneously or sequentially. In preferred embodiments, cutting and injection are integrated. This allows tissue cutting / bone fenestration to be performed in / along the implantation pathway. The dimensions of the tissue piece are such that it would be difficult to manipulate. Therefore, integrating cutting and implantation eliminates the need for additional manipulation. The tissue can be cut and loaded into the tissue delivery pathway without removing or manipulating the tissue outside the cutting device before being transferred to the intraocular appraiser. Using the same device, tissue to form a stent can be excised and then the stent injected / implanted into the eyeball, enabling seamless and intact loading of fine, micro-sized biostent tissue without passage manipulation.

[0122] The tissue may be, for example, the cornea, sclera, or other cartilage tissue. Tissue sections are cut using a delivery device and / or cutting device. The tissue is loaded into a tissue delivery pathway, at least partially containing the eyeball, without completely removing the tissue from the cutting device before transfer to the intraocular delivery device. In situations where a single, integrated bone fenestration / injector device is used, it is used for both bone fenestration of the tissue and for the injection and transplantation of the tissue into the eyeball.

[0123] In another embodiment, the bone perforation of the tissue and the insertion of the tissue into the eyeball are performed simultaneously or sequentially. A section of the tissue is cut and loaded into a tissue delivery pathway. This is performed using a device configured to excise the tissue and to load the excised tissue into an intraocular delivery applier for application of the tissue to the eye.

[0124] The applier device can also be used as a delivery device and loading platform device or conduit. In such an implantation, the device is configured to contain or otherwise accommodate tissue before implantation. The device allows for the longitudinal or other direction of movement of the tissue for implantation into the eyeball. The device may be configured for simultaneous or sequential fenestration and application loading of tissue so that, upon completion of the fenestration process, the fenestration or cut tissue is loaded into the delivery conduit of the applier device. The fenestration device can be coupled to an intraocular delivery device by a coupling or other attachment mechanism to facilitate the transfer of tissue into the delivery device.

[0125] Stents can be harvested from the patient during surgery using a bone fenestration device. Stents can also be formed from patches of material obtained from a donor or other tissue engineering source. The material patches can be pre-cut into a stent shape and pre-loaded within the area of ​​the delivery device. The material patches may also be cut during implantation using a bone fenestration device.

[0126] In this embodiment, with the pusher 320 in the lumen 328 of the outer tube 318 fully retracted to its proximal position, the patch of material 101 may be manually loaded through the cut-out window 326 of the outer tube 318. When the patch of material 101 is loaded into the delivery device 110, the shaft 310 and the patch of material 101 may be loaded into the bone perforation window cartridge 205. The cover 314 of the bone perforation window cartridge 205 can be removed from the base 324 to expose the recess 321 of the base 324. The shaft 310 of the delivery device 110 is positioned in slots 332, 334 such that the patch of material 101 is placed in the recess 321 between them.

[0127] The cover 314 of the bone perforation opening cartridge 205 is repositioned on the base 324 in a closed configuration, compressing and / or pulling the patch of material 101 within the bone perforation opening cartridge 205. The cutting member 312 is inserted through the hole 338 in the cover 314, and its blade 344 can be biased through the cover 314 toward the patch of material 101. The cutting member 312 can be seated within the bone perforation opening cartridge 205 so that the blade 344 of the cutting member 312 completely cuts through the patch of material 101. With the blade 344 still in the full cut position relative to the bone perforation opening cartridge 205, the pusher 320 is biased distally to prepare the shaft 310, positioning the now-cut stent 105 within the lumen of the outer tube 318 toward the opening from the lumen 328 near the most distal end of the tube 318. The delivery device 110 is now ready for use on the patient.

[0128] In this embodiment, a patch of material 101 may be loaded into a recess 1321 of the delivery device 1110. The access door 1314 may be opened and the patch of material 101 may be placed into the recess 1321. The door 1314 may be closed to capture the patch of material 101 in the recess 1321 and compress it at least partially. The stretcher 1350 may be actuated to apply tension to the patch of material 101 before it is cut by the cutter tube 1312. The cutter tube 1312 is actuated to slide distally, thereby cutting the patch of material 101 into the stent 105. The pusher 1320 can then be distally biased to bias the shaft 1310 by positioning the cut stent 105 within the distal end region of the lumen 1382 of the introducer tube 1380. Once advanced distal to the rigid outer tube 1318, the pusher 1320 can be relaxed into a curved shape, thereby encouraging the introduction tube 1380 to also adopt this curved shape. The delivery device 110 is now ready for use in the patient. The introduction tube 1380 may have a flexible and / or curved shape in its distal end region and may be configured to conform to the shape of the desired implantation site, such as the curvature of the eye near the anterior horn, as described above.

[0129] Generally, the stent 105, positioned within the shaft of the delivery device, can be implanted through a transparent corneal or scleral incision formed using the delivery device or a separate device. A viewing lens, such as an angle lens, can be positioned adjacent to the cornea. The viewing lens allows visualization of internal eye regions, such as the scleral pulsation and scleral junction, from an anterior position within the eye. The viewing lens may optionally include one or more guide channels sized to receive the shaft of the delivery device. An endoscope may also be used during delivery to aid visualization. Ultrasound guidance can also be used with a high-resolution biomicroscope, OCT, etc. Alternatively, a small endoscope may be inserted through another marginal incision in the eyeball to image the eyeball during implantation.

[0130] The distal tip of the shaft holding the stent 105 can penetrate the cornea (or sclera) to access the anterior chamber. In this regard, a single incision can be made within the eyeball, such as within the corneal margin. In embodiments, the incision is located very close to the margin, such as at the level of the margin of the clear cornea or within 2 mm of the margin. Either the shaft or a separate cutting device is used to make the incision. For example, to enter the cornea, a knife-tip device or a diamond knife can be used first. Then, a second device with a spatula tip can be advanced over the knife tip, positioned so that the spatula plane coincides with the anatomical plane.

[0131] The corneal incision can be large enough to allow the shaft to pass through. In one embodiment, the incision is about 1 mm in size. In another embodiment, the incision is about 2.85 mm or less in size. In yet another embodiment, the incision is not larger than about 2.85 mm and is larger than about 1.5 mm. Incisions up to 2.85 mm have been observed to be self-sealing incisions.

[0132] After insertion through the incision, the shaft advances into the anterior chamber along a pathway that allows the stent 105 to be delivered from the anterior chamber to a target location such as the supraclavicular or suprachoroidal space. With the shaft positioned for the approach, the shaft is further advanced into the eye so that its distal tip penetrates the tissue of the canthus, for example, the iris root or ciliary body region or the iris root near the tissue boundary with the scleral pulsation.

[0133] The scleral process is an anatomical landmark on the wall of the canthus of the eye. It is above the level of the iris but below the level of the cavernous retina. In some eyes, the scleral process is obscured by the inferior zone of the pigmented cavernous retina, which is located directly behind it. While the shaft can be moved along the canthus and scleral process, passing near it on its way to the supracial space, it does not necessarily penetrate the scleral process during delivery. Rather, the shaft can move downward in contact with the scleral process, dissecting the tissue boundary between the sclera and the ciliary body, with the dissection entry point beginning directly below the scleral process, near the iris root or iris root portion of the ciliary body. In another embodiment, the implant delivery route crosses the scleral process.

[0134] The shaft can approach the corner of the eyeball from the anterior chamber on the same side as the deployment site, eliminating the need to advance the shaft across the iris. Alternatively, the shaft can approach the corner of the eye by crossing the anterior chamber AC so that the shaft can advance across the iris and / or anterior chamber toward the opposite corner of the eye. The shaft can approach the corner of the eyeball via various routes. The shaft does not necessarily have to cross over the eyeball or intersect the central axis of the eyeball. In other words, the corneal incision and the location where the stent 105 is implanted at the corner of the eyeball can be in the same quadrant when viewed toward the eyeball along the optical axis. Furthermore, it is desirable that the path of the stent 105 from the corneal incision to the corner of the eyeball does not pass through the central line of the eyeball to avoid interference with the pupil.

[0135] The shaft can be advanced continuously into the eyeball, for example, by about 6 mm. The anatomical surface of the shaft can be positioned to follow the curve of the inner scleral wall, allowing for unreserved dissection of the boundary between the scleral process and the tissue layers of the ciliary body CB, such that after penetrating, for example, the iris root or iris root portion of the ciliary body CB, the stent 105 attached to the shaft extends through the supraciliary space and further on, positioned between the tissue boundary of the sclera and choroid, forming the suprachoroidal space.

[0136] Once properly positioned, the stent 105 is released. In some embodiments, the stent 105 can be released by withdrawing the outer tube 318 from the shaft 310, while the pusher 320 prevents the stent 105 from being pulled out together with the outer tube 318. In other embodiments, as described elsewhere in this specification, the stent 105 can be released by pulling out the introduction tube 1380 while the pusher 1320 remains stationary.

[0137] Once implanted, stent 105 forms a fluid communication pathway between the anterior chamber and the target pathway (e.g., the supraclavicular or suprachorionic space). As previously stated, stent 105 is not limited to being implanted in the suprachorionic or supraclavicular space. Stent 105 can be implanted in other locations that provide fluid communication between the anterior chamber and the ocular location, such as Schlemm's canal or a subconjunctival location in the eye. In another embodiment, stent 105 is implanted to form a fluid communication pathway between the anterior chamber and Schlemm's canal and / or a communication pathway between the anterior chamber and the subconjunctival location in the eye. It should be understood that the devices described herein can also be used to deliver the stent transsclerolytically as well as through an internal approach.

[0138] As mentioned above, the material used to form the stent can be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

[0139] A wide variety of systemic and ocular conditions, including inflammation, infection, and cancerous growth, can be prevented or treated using the stents described herein. More specifically, ocular conditions such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystic macular edema, and herpes simplex virus and adenovirus infections can be treated or prevented.

[0140] The following classes of drugs can be delivered using the devices of the present invention: antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport / mobility impulse enhancers such as colchicine, vincristine, cytochalasin B and related compounds, beta-blockers such as timolol, betaxolol, and atenolol, antiglaucoma drugs such as prostaglandin analogs such as bimatoprost, travoprost, and latanoprost; carbonic anhydrase inhibitors such as acetazolamide, metazolamide, dichlorphenamide, and diamox; neuroprotective agents such as nimodipine and related compounds. Further examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; and antimicrobial agents such as sulfonamides, sulfacetamide, sulfamethizol, and sulfisoxazole. Antifungal agents such as fluconazole, nitrofurazone, amphotericin B, ketoconazole, and related compounds; antiviral agents such as trifluorothymidine, acyclovir, ganciclovir, DDI, AZT, foscamet, vidarabine, trifluorolysine, idokithizine, ribavirin, protease inhibitors, and anticytomegalovirus agents; antiallergens such as metapyriline. Antiallergic agents such as chlorpheniramine, pyramine, and profenpyridamine; anti-inflammatory agents such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, fluorometholone, betamethasone, and triamcinolone; antipyretic analgesics such as phenylephrine, naphazoline, and tetrahydrazoline. Antibiotics and anticholinesterases such as pilocarpine, carbachol, diisopropyl fluorophosphate, phospholine iodide, and demepotassium bromide. Mydriatics such as atropine sulfate, cyclopentolate, homatropin, scopolamine, tropicamide, and eucatropin; sympathomimetic agents such as epinephrine, vasoconstrictors, and vasodilators; ranibizumab, bevacizumab, and triamcivirone.

[0141] Nonsteroidal anti-inflammatory drugs (NSAIDs) may also be delivered, such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, e.g., ASPIRIN®, Bayer, Leverkusen, Germany; ibuprofen, e.g., ADVIL®, Weiss, Collegeville, Perth; indomethacin; mefenamic acid), COX-2 inhibitors (CELEBREX®, Pharmacia, P-Pak, New Jersey; COX-1 inhibitors), the prodrug Nepafenac®, immunosuppressants, e.g., Cirolimas (RAPAMUNE®, Weiss, Collegeville, Pennsylvania), or MMP inhibitors that act early in the inflammatory response pathway (e.g., tetracycline and tetracycline derivatives). Anticoagulants such as heparin, antifibrinogen, fibrinolysin, and anticoagulant activases may also be delivered.

[0142] Antidiabetic agents that can be delivered using the apparatus of the present invention include acetohexamide, chlorpropamide, glipizide, glibride, trazamide, tolbutamide, insulin, aldose reductase inhibitors, etc. Examples of anticancer agents include 5-fluorouracil, adriamycin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, estramustine, etoposide, etretinate, filgrastine, phloxlysine, and fludarabine. Fluorouracil, fluoxymesterone, flutamide, goserelin, hydroxyurea, ifosfamide, leuprolide, levamisol, lomustine, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitomycin. Mitotane, pentostatin, pipobromane, plicamycin, procarbazine, salglamostine, streptozocin, tamoxifen, taxol, teniposide, thioguanine, uracil mustard, vinblastine, vincristine, and vindesine.

[0143] Hormones, peptides, nucleic acids, sugars, lipids, glycolipids, glycoproteins, and other macromolecules can be delivered using the devices of the present invention. Examples include: endocrine hormones such as pituitary hormone, insulin, insulin-related growth factor, thyroid hormone, and growth hormone; heat shock proteins; muramyl dipeptides, cyclosporine, interferons (including α, β, and γ interferons), interleukin-2, cytokines, FK506 (epoxypyrido-oxazacyclotricosin-tetron, also known as tacrolimus), tumor necrosis factor, pentostatin, timopentin, transforming factor β2, and immunomodulatory factors such as erythropoietin; anti-neogeneic proteins (e.g., anti-VEGF, interferon), and anticlotting agents, including anticlotting activases, among others. Further examples of macromolecules that can be delivered include monoclonal antibodies, brain nerve growth factor (BNGF), ceria nerve growth factor (CNGF), vascular endothelial growth factor (VEGF), and monoclonal antibodies directed against such growth factors. Examples of adding immunomodulatory agents include tumor necrosis factor inhibitors such as thalidomide.

[0144] Various embodiments will be described with reference to the drawings. However, certain embodiments may be implemented without one or more of these specific details, or in combination with other known methods and configurations. The description includes numerous specific details, such as particular configurations, dimensions, and processes, in order to provide a complete understanding of the embodiments. In other examples, well-known processes and manufacturing techniques are not described in particular detail so as not to unnecessarily obscure the description. Throughout this specification, references to “one embodiment,” “one implementation,” “one service,” etc., mean that the particular features, structures, configurations, or characteristics described are included in at least one embodiment or implementation. Therefore, expressions such as “one embodiment,” “one implementation,” “one service,” etc., appearing elsewhere in this specification do not necessarily refer to the same embodiment or implementation. Furthermore, certain features, structures, configurations, or characteristics may be combined in any suitable way in one or more implementations.

[0145] The use of relative terms throughout this specification may indicate relative positions or orientations. For example, “distal” may indicate a first direction away from a reference point. Similarly, “proximal” may indicate a position in a second direction opposite to the first direction. The reference point used herein may be the operator, so that the terms “proximal” and “distal” refer to the operator using the device. Areas of the device close to the operator may be referred to herein as “proximal,” and areas of the device away from the operator may be referred to herein as “distal.” Similarly, the terms “proximal” and “distal” may also be used herein to refer to the anatomical position of the patient from the operator's perspective or along the insertion path from the system’s entry point. Thus, a position that is proximal may mean a patient position close to the device’s entry point along the insertion path toward the target, and a position that is distal may mean a patient position far from the device’s entry point along the insertion path toward the target position. However, such terms are provided to establish a relative reference frame and are not intended to limit the use or orientation of the device to specific configurations described in the various embodiments.

[0146] This specification contains many specific details, but these should not be interpreted as limitations on the scope of what is claimed or can be claimed, but rather as descriptions of features specific to particular embodiments. Certain features described herein in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented separately or in any suitable subcombination in multiple embodiments. Furthermore, features are described above as acting in a particular combination, and may initially be claimed as such, but one or more features from the claimed combination may, in some cases, be removed from the combination, and the claimed combination may be directed towards a subcombination or a variation of a subcombination. Similarly, operations are depicted in the drawings in a particular order, but this should not be understood as requiring that such operations be performed in the specific order shown, or sequentially, or all illustrated operations be performed in order to achieve the desired result. Only a small number of examples and embodiments are disclosed. Variations, modifications, and enhancements to the described examples and implementations, as well as other implementations, may be made based on the disclosed content.

[0147] In the above description and claims, phrases such as “at least one of” or “one or more of” may be followed by a conjunctive list of elements or features. The term “and / or” may also appear in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such phrases are intended to mean any of the listed elements or features individually, or any of the implicit elements or features in combination with any of the other implicit elements or features. For example, the phrases “at least one of A and B”; “one or more of A and B”; and “A and / or B” are intended to mean “A alone, B alone, or A and B together,” respectively. A similar interpretation is intended for lists containing three or more items. For example, the usages "at least one of A, B, and C," "one or more of A, B, and C," and "A, B, and / or C" are intended to mean "A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together," respectively.

[0148] The use of the term “based on” in the foregoing and in the claims is intended to mean “at least partially based on” so as to allow for features or elements that are not cited.

[0149] The systems disclosed herein may be packaged together in a single package. The finished package will be sterilized using a sterilization method such as ethylene oxide or radiation, labeled, and boxed. Instructions for use may also be provided inside the box or via an internet link printed on the label.

Claims

1. A method for preparing an implant to be transplanted into a patient's eye, A step of cutting a biological material using at least one cutting member to form an implant from the biological material, wherein the implant has an elongated shape having a length between a first end and a second opposite end, and a thickness between the upper and lower surfaces of the implant; A step of loading an implant into the distal portion of a delivery device, wherein the distal portion has a size and shape for insertion into the anterior chamber of the eye, and the distal portion includes a lumen and stopper within an elongated tubular member; and, The process includes positioning the implant in a lumen at a preparatory position near the distal end region of the lumen, wherein the thickness of the implant substantially covers the inner diameter of the elongated tubular member, and the stopper is positioned proximal to the first end of the implant; The elongated tubular member is retracted over the implant and stopper, thereby exposing the implant from the lumen. A method using bio-derived materials that includes a rigid structure allowing the implant to function as a structural spacer that facilitates the outflow of aqueous humor from the anterior chamber through the treatment site during deployment.

2. The method according to claim 1, wherein at least one cutting member includes at least one pair of opposing cutting edges, thereby ensuring that the central portion of the biomaterial between the pair of opposing cutting edges is an implant when cutting the biomaterial using at least one cutting member.

3. The method according to claim 1, wherein the biologically derived material comprises tissue taken from a donor or patient, and the donor tissue is an allograft or xenograft material.

4. The method according to claim 3, wherein the tissue comprises scleral or corneal tissue.

5. The method according to claim 1, comprising one or more therapeutic agents.

6. The method according to claim 1, wherein the delivery device includes an actuator which is at least one of a wheel, a slide, or a button.

7. The method according to claim 1, wherein the distal end of the elongated tubular member is blunted so as to be able to incise eye tissue at the treatment site.

8. The method according to claim 1, wherein the thickness is approximately 100 to 800 micrometers.

9. The method according to claim 1, wherein the inner diameter of the elongated tubular member is less than approximately 0.036 inches (0.9 mm) to approximately 0.009 inches (0.23 mm).

10. The method according to claim 1, wherein the length is approximately 1 mm to approximately 10 mm.

11. The method according to claim 1, wherein the treatment site includes a cyclodialysis rupture.

12. The method according to claim 11, wherein the first end of the implant is located in the anterior chamber of the eye, and the second opposite end of the implant is located between the sclera and the ciliary body or between the sclera and the choroid.

13. The method according to claim 1, wherein the treatment site includes the canthus of the eye near Schlemm's canal or the iris-scleral junction.

14. The method according to claim 1, wherein the biologically derived material has permeability that allows water to drain from the eye through the implant when the implant is placed in the treatment site.

15. The method according to claim 1, wherein the biologically derived material is scleral tissue or corneal tissue that shrinks from a first thickness to a second thickness after cutting, and the first thickness is greater than the second thickness.

16. The method according to claim 15, wherein the first thickness is about 400 microns and the second thickness is about 250 to 300 microns.

17. The method according to claim 1, wherein the distal portion has a size and shape that allows it to be inserted into the anterior chamber through a corneal incision, and the corneal incision is self-closing.

18. The method according to claim 17, wherein the corneal incision is not greater than 2.85 mm and is greater than approximately 1.5 mm.

Images