System for shaping and implanting a biological intraocular stent for increasing aqueous humor outflow and reducing intraocular pressure

Abstract

A system and method for preparing and inserting an implant into a patient's eye from within the eye, the system including a tissue cartridge configured to receive and hold a patch of substance, a cutting device, and a delivery device. Related devices, systems, and methods are provided.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63 / 027,689, filed May 20, 2020, and U.S. Provisional Patent Application No. 63 / 163,623, filed March 19, 2021, both of which are co - pending. The disclosure of this application is incorporated herein by reference in its entirety.

Background Art

[0002] The mainstay of glaucoma eye surgery is to increase the outflow of aqueous humor from the eye. There are various approaches to such surgery: 1) trabeculectomy or shunting from the outside of the eye, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a trans - scleral outflow pathway; 2) stenting or shunting the outflow of aqueous humor between the trabecular meshwork or through the sclera from the inside of the eye using hardware - based implantable devices or ablating non - implantable cutters such as dual - blade and trabectome; and 3) stenting the suprachoroidal space from the inside of the eye using implants of transplantable non - biological hardware.

[0003] Current stenting devices and methods from the inside of the eye are based on non - biological hardware materials such as polyimide, polyethersulfone, titanium, polystyrene - block - isobutylene - block - styrene. Implantable devices based on non - biological hardware have significant drawbacks, which can lead to damage to eye tissues such as major erosion, fibrosis, and loss of endothelial cells.

[0004] In view of the above, improved devices and methods related to eye surgery for the treatment of glaucoma are needed.

Summary of the Invention

[0005] In one aspect, a system for preparing a graft and inserting the graft into a patient's eye from the inside of the eye is described. The system includes a tissue cartridge configured to receive and hold a patch of material, a cutting device, and a delivery device.

[0006] The tissue cartridge can include a shaft extending from the distal end of the tissue cartridge. At least the distal end region of the shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft can include a lumen. The tissue cartridge can further include a base and a cover. The base can be configured to receive the patch, and the cover can be configured to secure and hold the patch to the base. The cutting device can include a cutting member configured to cut a patch of material located within the tissue cartridge. By cutting the patch of material with the cutting member, a graft can be formed from the patch. The graft can be configured to be implanted into the patient's eye. The delivery device can include an actuator configured to deploy a graft located within the cartridge into the eye through the lumen of the shaft.

[0007] In an example of an interrelated implementation, a method of preparing a graft for implantation into a patient's eye and inserting the graft into the patient's eye is described. The method includes inserting a patch of material into a tissue cartridge. The tissue cartridge includes a shaft extending from a distal end of the tissue cartridge. At least a distal end region of the shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft includes a lumen. The method further includes coupling the tissue cartridge with a cutting device. The cutting device has a cutting member configured to cut the patch of material within the tissue cartridge. The method further includes cutting the patch with the cutting member to form a graft from the patch while the tissue cartridge and the cutting device are coupled, decoupling the tissue cartridge from the cutting device, coupling the tissue cartridge with a delivery device, inserting the distal end region of the shaft into the anterior chamber, positioning the distal end region adjacent to eye tissue, and actuating the delivery device to deploy the graft from the cartridge through at least a portion of the lumen such that the graft engages the eye tissue. The method can further include delivering an adhesive substance through the shaft.

[0008] In an example of an interrelated implementation, a system for preparing a graft and inserting the graft into a patient's eye from the inside of the eye is described. The system includes a tissue cartridge configured to receive and hold a patch of material and a delivery device.

[0009] The tissue cartridge can include a shaft extending from the distal end of the tissue cartridge. At least the distal end region of the shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft can include a lumen. The tissue cartridge can further include a base and a cover. The base can be configured to receive a patch, and the cover can be configured to secure and hold the patch to the base. The system can further include a cutting device. The cutting device can include a cutting member configured to cut a patch of material located within the tissue cartridge. By cutting the patch of material with the cutting member, a graft can be formed from the patch. The graft can be configured to be transplanted into a patient's eye. The delivery device can include an actuator configured to deploy a graft located within at least a portion of the cartridge through the lumen of the shaft into the eye. The tissue cartridge can include a nose cone assembly having a distal end region of the tissue cartridge and the shaft. The nose cone assembly can be reversibly coupled to the tissue cartridge and reversibly coupled to the delivery device. The shaft of the tissue cartridge can be configured to deliver an adhesive substance.

[0010] In an example of interrelation, a method of preparing a graft for implantation into a patient's eye and inserting the graft into the patient's eye is described. The method includes inserting a patch of material into a tissue cartridge. The tissue cartridge includes a shaft extending from a distal end of the tissue cartridge. At least a distal end region of the shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft includes a lumen. The method includes coupling the tissue cartridge with a cutting device. The cutting device has a cutting member configured to cut the patch of material within the tissue cartridge. The method includes cutting the patch with the cutting member to form a graft from the patch while the tissue cartridge and the cutting device are coupled, separating at least a portion of the tissue cartridge from the cutting device, coupling at least a portion of the tissue cartridge with a delivery device, inserting the distal end region of the shaft into the anterior chamber, positioning the distal end region adjacent to eye tissue, and actuating the delivery device to deploy the graft from the cartridge through at least a portion of the lumen such that the graft engages the eye tissue. The method can further include delivering an adhesive substance through the shaft.

[0011] In an example of interrelation, a system for preparing a graft from a patch of material and implanting the graft into a patient's eye from the inside of the eye is described that includes a nose cone, a tissue cartridge having a distal shaft that defines a lumen between the nose cone and a distal end region of the distal shaft, a cutting device configured to couple to the nose cone, and a delivery device configured to couple to the nose cone.

[0012] At least the distal end region of the distal shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The cutting device can include a base configured to receive the patch. The cutting device can include a cutting member configured to cut a patch of material into the implant. The cutting device can further include a compacting tool configured to urge the implant into the lumen of the distal shaft. The delivery device can include an actuator configured to deploy the implant, compressed within the lumen of the distal shaft, into the eye.

[0013] In related implementations, a method of preparing an implant from a patch of material for implantation into a patient's eye and inserting the implant into the patient's eye is described. The method includes coupling a tissue cartridge and a cutting device, the tissue cartridge having a shaft extending from a distal end of the tissue cartridge, at least the distal end region of the shaft being dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft includes a lumen and the cutting device has a cutting member configured to cut the patch of material. The method further includes cutting the patch with the cutting member to form the implant from the patch, compressing the implant within the lumen of the shaft, detaching the tissue cartridge from the cutting device, coupling the tissue cartridge and a delivery device, inserting the distal end region of the shaft into the anterior chamber, positioning the distal end region adjacent to the eye tissue, and actuating the delivery device to deploy the implant from the lumen such that the implant engages the eye tissue. The method can further include delivering an adhesive substance through the shaft.

[0014] In an example of interrelation, a system for preparing a graft and inserting the graft into a patient's eye from the inside of the eye, including a tissue cartridge and a delivery device, is described. The tissue cartridge can include a shaft extending from a distal end of the tissue cartridge, and at least a distal end region of the shaft is dimensioned and shaped to be inserted into the anterior chamber of the eye. The shaft can include a lumen. The system can further include a cutting device having a cutting member configured to cut a patch of material. By cutting the patch of material with the cutting member, a graft can be formed from the patch configured to be implanted into the patient's eye. The delivery device can include an actuator configured to deploy a graft located within the shaft through the lumen of the shaft into the eye. The tissue cartridge can include a nose cone assembly having a distal end region of the tissue cartridge and the shaft. The nose cone assembly can be reversibly coupled to the tissue cartridge and reversibly coupled to the delivery device. The shaft of the tissue cartridge can be configured to deliver an adhesive substance.

[0015] In an example of interrelation, a method of preparing a graft for implantation into a patient's eye and inserting the graft into the patient's eye is described, including cutting a patch of material with a cutting member of a cutting device to form a graft from the patch, compressing the graft within a lumen of a shaft extending from a distal end of a tissue cartridge, detaching at least a portion of the tissue cartridge from the cutting device, coupling at least a portion of the tissue cartridge with a delivery device, inserting a distal end region of the shaft into the anterior chamber of the eye, positioning the distal end region adjacent to eye tissue, and actuating the delivery device to deploy the graft from the tissue cartridge through at least a portion of the lumen such that the graft engages the eye tissue. The method can further include delivering an adhesive substance through the shaft.

[0016] In an example of interrelation, a method of treating an eye using minimally-modified biological tissue is described. The biological tissue can be scleral tissue. Minimally modifying the scleral tissue can include compressing the scleral tissue within the distal shaft from a first dimension to a second, smaller dimension. The distal shaft is sized and shaped to be inserted into the anterior chamber of the eye through a self-sealing incision in the cornea of the eye. The method can further include deploying the compressed scleral tissue from the distal shaft between tissue layers near the iridocorneal angle. The compressed scleral tissue deployed from the distal shaft can return toward the first dimension. The method can further include treating glaucoma using the compressed scleral tissue.

[0017] In some variations, in the above methods, devices, apparatuses, and systems, one or more of the following can optionally be included in an executable combination. Further details are described in the accompanying drawings and the following detailed description. Other features and advantages will become apparent from the detailed description and the drawings.

Brief Description of the Drawings

[0018] These and other aspects are described in detail with reference to the following drawings. Generally, the drawings are not to absolute or relative scale and are for illustrative purposes. Also, the relative arrangement of features and elements may be changed to clarify the description.

[0019]

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DETAILED DESCRIPTION OF THE INVENTION

[0020] It should be understood that the drawings are merely examples and are not intended to be to scale. It should be understood that the devices described in this specification may include functions not necessarily shown in each figure.

[0021] Implants, systems, and methods for increasing aqueous humor outflow from the anterior chamber of the eye are disclosed. As will be described in detail below, placement of an outflow stent from the inside of the eye using biological, cell-based, or tissue-based materials provides biocompatible increased aqueous humor outflow with improved tolerability and safety compared to conventional shunts. In an example, the 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 cutting device, also referred to herein as a trephining device or cutting tool. In an example, the stent is an elongated body or material having an internal lumen that provides a drainage pathway. In a preferred example, the stent is an elongated body or strip of tissue configured to provide supra-ciliary stent placement without an internal lumen, maintaining a slit. The lumen-based device may be limited by the lumen that functions as a pathway for fibrotic occlusion. The stent formed from tissue is implanted into the eye via a delivery pathway from the inside of the eye, and aqueous humor flows out from the anterior chamber. The stents described herein can be used as phacoemulsification aids for glaucoma as a minimally invasive glaucoma surgery (MIGS) procedure or as an independent procedure.

[0022] The use of terms such as stent, implant, shunt, biological tissue, tissue, etc. is not intended to be limited to any one structure or substance. The structure to be implanted can be a substance that is substantially absorbed by the eye tissue after being placed in the eye such that, when absorbed, a space remains at the location where the structure was previously located, but this is not necessarily the case. Once implanted, the structure can also remain in place for an extended period of time and not be substantially eroded or absorbed.

[0023] As will be described in more detail below, the stents described in the present application can be made from biologically derived materials that do not cause toxic or harmful effects after being implanted in a patient.

[0024] The term "biologically derived substance" includes natural biological substances, synthesized biological substances, and combinations thereof that are suitable for transplantation into the eye. Biologically derived substances include natural biological structures and structures having a biological arrangement naturally found within a mammalian subject, including organs or parts of organs formed of tissue, and substances formed of tissues grouped together according to function. Biologically derived substances include tissues such as corneal, scleral, or cartilage tissue. The tissues contemplated in the present application can include any of a variety of tissues, including muscle tissue, epithelial tissue, connective tissue, and nerve tissue. Biologically derived substances include tissues from a subject, including tissues, organs, parts of organs, and autologous, allogeneic, and xenogeneic transplantable tissue pieces harvested from a donor or patient. Biologically derived substances include naturally occurring biological substances, including any substances naturally found within the body of a mammal. Biologically derived substances used in the present application also include substances designed to have a biological arrangement similar to a natural biological structure. For example, substances can be synthesized using in vitro techniques such as seeding a three-dimensional scaffold or matrix with appropriate cells, engineered substances, or 3D printed substances to form a transplantable bioconstruct. Biologically derived substances used in the present application also include cell-derived substances, including stem cell-derived substances. In some examples, biologically derived substances include injectable hyaluronic acid hydrogels, or adhesive substances such as cross-linked hyaluronic acid (dimer) of GEL-ONE.

[0025] In some examples, the biostent may be an engineered or 3D printed material formed in the shape of a tube having a lumen extending from a proximal opening to a distal opening. The tube may be printed to incorporate a plurality of openings throughout. For example, the walls of the printed material can be configured to have a plurality of openings such that the liquid within the lumen penetrates or flows out through the walls of the tube to ensure that the tube is sufficiently porous to allow for drainage of water from the eye. The tube may be printed to have dimensions that change during or near delivery. For example, the 3D printed material may be designed to have a first dimension that is convenient for manual manipulation. During or near delivery, the 3D printed material may be cut to dimensions suitable for implantation into the eye. If a patch of material is described as being cut or trephined to the stent prior to implantation, it should be understood that the patch of material can be a printed material having a particular three-dimensional shape (including, for example, tubular) and is cut to the stent by cutting it to a shorter, desired length. Thus, in certain examples, the stents described herein need not be solid and can incorporate a lumen.

[0026] Biological materials, sometimes referred to herein as biological tissues or biomaterials, used to form the stents, can be diverse and can include, for example, corneal tissue, scleral tissue, cartilage tissue, collagen tissue, or other rigid biological tissues. The biological tissue can be made hydrophilic or hydrophobic. The biological tissue can contain or be impregnated with one or more therapeutic agents for additional treatment of the eye disease process.

[0027] The material of the biostent can be used in combination with one or more therapeutic agents and can be used to additionally deliver the agent to the eye. In an example, the biological tissue can be implanted with sustained release pellets or impregnated with a therapeutic agent for sustained release delivery to the target tissue.

[0028] A non-biological substance includes synthetic substances prepared by artificial synthesis, processing, or manufacturing that may be biologically compatible, but the synthetic substances are not cell-based or tissue-based. For example, non-biological substances include polymers, copolymers, polymer blends, and plastics. Non-biological substances include inorganic polymers such as silicone rubber, polysiloxane, polysilane, and organic polymers such as polyethylene, polypropylene, polyvinyl, polyimide.

[0029] Biologically derived substances, regardless of their source or type, can be cut or trephined into an elongated shape suitable for stent placement and transplantation into the eye. This cutting procedure of the tissue can be performed either before or during a surgical transplantation procedure. The stent(s) implanted in the eye may have a structure and / or permeability that allows the outflow of aqueous humor from the anterior chamber when located within the cyclodialysis cleft.

[0030] Biological substances can be tissues that have been minimally modified or minimally manipulated for use in the eye. Minimally modified biological substances do not include combinations with other articles, except for, for example, water, sterilizing agents, preservatives, cryopreservatives, preservatives, and / or pharmaceuticals / therapeutics (plural possible). Minimally modified biological substances, once implanted, do not have a systemic effect and do not depend on the metabolic activity of any living cells for their main function. Biological substances are carried out with minimal manipulation to maintain the original relevant characteristics of the biological tissue at each stage of the preparation method and the use method. A cut stent can be made into a structural tissue that physically supports or functions as a barrier or conduit, for example, by at least partially maintaining the zonular dialysis cleft formed in the eye. A stent cut from a biological substance can be subjected to minimal operations such as compression, compacting, folding, rolling, or other types of temporary operations that allow the substance to return towards its original structure when a force is applied to supply compression or compacting. Thus, with minimal operations, the dimensions or shape of the cut tissue can be temporarily mechanically changed, but after being released from that mechanical change, the original relevant characteristics of the tissue regarding its usefulness for reconstruction, repair, or replacement can be maintained. As an example, a biological substance can be made into a sclera cut into a shape dimensioned larger than the inner diameter of the delivery tube into which the stent is implanted. Minimal operations on the cut stent can include temporarily compacting the scleral substance into the lumen of the delivery shaft so that after implantation in the eye, the cut stent has a tendency to return towards its original cut dimensions. Biological substances are described in this application in the context of being cut into stents such as implants that can maintain a tear for aqueous humor outflow, but other methods are also contemplated in this application. For example, biological substances can be compressed into plugs implanted in the eye region for other purposes such as stents, occlusion of traumatic ruptures, overfiltration blebs, posterior wall ruptures, and other indications.

[0031] Figures 1A and 1B are cross-sectional views showing the anterior chamber AC and the vitreous body VC of the human eye. The stent 105 can be positioned inside the eye at the implantation site such that at least a first portion of the stent 105 is located within the anterior chamber AC and a second portion of the stent 105 is located within a tissue such as the suprachoroidal space and / or the suprachoroidal space. The stent 105 is configured in dimensions and shape to be positioned in such a configuration. The stent 105 provides a passage for the flow of aqueous humor away from the anterior chamber AC (e.g., to the suprachoroidal space and / or the suprachoroidal space), or else functions as such a passage. In FIGS. 1A and 1B, the stent 105 is schematically shown as an elongated body relative to the delivery shaft 210. It should be understood that the dimensions and shape of the stent 105 can be varied. Further, the dimensions and shape of the stent 105 prior to insertion into the delivery shaft 210 can change upon insertion into the delivery shaft 210 and can change after deployment from the delivery shaft 210.

[0032] The stent 105 can be implanted into the eye from the inside, for example, through a clear corneal incision or sclerotomy. The stent can be implanted to form an opening or tear for increased outflow communication between the anterior chamber AC and the suprachoroidal space, the anterior chamber AC and the suprachoroidal space, the anterior chamber AC and Schlemm's canal, or the anterior chamber AC and the subconjunctival space, or other ocular compartments, tissues or interfaces where transscleral, sub-scleral, or supra-scleral occlusion, stenting, and / or tissue reinforcement are clinically indicated. In a preferred example, the stent 105 is implanted such that the distal end is located within the supraciliary position and the proximal end is located within the anterior chamber AC to provide a supraciliary tear. The distal end of the stent 105 can be located between other anatomical parts of the eye.

[0033] Conventional glaucoma stent placement devices are generally formed of non-biological materials or synthetic materials such as polyimide, which cause damage to endothelial tissue and result in progressive, long-term, irreversible loss of corneal endothelium. The stent material described in the present application can reduce and / or eliminate the risk of these tissue damages while still providing increased aqueous humor outflow.

[0034] The stent 105 described in the present application can be formed of any of a variety of biologically derived materials having a permeability and / or structure such that water can filter therethrough. The stent 105 can be formed of a biologically derived material that has been harvested, engineered, cultivated, or otherwise produced. The biologically derived stent material can be obtained or harvested from a patient or donor. The biologically derived stent material can be harvested before or during surgery. The biologically derived stent material can also be made into a synthetic biological tissue created using in vitro techniques. The biologically derived material can be generated from stem cells or be bioengineered. The tissue can be generated by in situ cell growth or acellular growth. In an example, the tissue can be 3D printed during manufacture. The biologically derived material can be a minimally manipulated material and can retain its original structural properties as tissue.

[0035] The 3D printed tissue can be printed as a larger patch that is cut during surgery, as described elsewhere in the present application. Alternatively, the 3D printed tissue can be printed to the final dimensions of the implant stent. In this example, there is no need to cut the 3D printed material prior to implantation, and it can be implanted as is. For example, the 3D printed stent can be printed directly into a cartridge configured to operate in conjunction with the delivery device described in the present application, which is used sequentially to deploy the 3D printed stent into the eye. The 3D printed stent can be generated using the 3D printing process described in Biofabrication, Volume 11, Issue 3, 2019.

[0036] In an embodiment, the stent 105 is made of biological tissue. The biologically derived material can be corneal tissue and / or tissue other than the cornea. The biologically derived material can include corneal tissue, scleral tissue, collagen fiber tissue, cartilage tissue, and the like. In an example, the biologically derived stent material can be a denatured corneal stromal tissue without epithelium and endothelium, which is porous and has hydrophilic permeability that allows water filtration. The biologically derived material can be a minimally manipulated sclera that retains its original structural properties as a tissue. The biologically derived material of the stent 105 can be incorporated into the eye's native anatomical structure after being positioned in the eye, but it does not necessarily have to be incorporated. Even after the stent is absorbed, the stent enables the surrounding tissue to form a path that remains open for an extended period. The biologically derived stent material may not be significantly absorbed or incorporated into the eye's anatomical structure such that the stent 105 remains implanted for a long term or indefinitely, if desired.

[0037] In other examples, the material of the stent 105 may be made of a complex carbohydrate or collagen that is non-inflammatory. The stent 105 may also be a homo- or copolymer such as hydroxyaliphatic carboxylic acid, polylactic acid, polyglycolic acid, polylactic glycolic acid, crosslinked or uncrosslinked sodium carboxymethylcellulose, carboxymethylcellulose starch, cellulose ether, cellulose such as cellulose esters such as cellulose acetate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, or cellulose derivatives such as ethylcellulose, polysaccharides such as calcium alginate, polypropylene, polybutyrate, polycarbonate, acrylate polymers such as polymethacrylate, polyanhydrides, polyvalerates, polycaprolactones such as polycaprolactone, polydimethylsiloxane, polyamide, polyvinylpyrrolidone, polyvinyl alcohol phthalate, waxes such as paraffin wax, white beeswax, natural oils, shellac, zein, or mixtures thereof, and may be formed of a biodegradable or bioabsorbable material including a biodegradable polymer. The stent 105 may be formed of a hyaluronic acid hydrogel or a visco material.

[0038] As described above, the stent material derived from an organism can have permeability or porosity that allows for water filtration for sufficient control or regulation of intraocular pressure. The permeable biological tissues (e.g., sclera, cornea, collagen, etc.) described in the present application are preferred stent materials, but any biological tissue, even if impermeable, is considered in the present application as a potential stent material that functions as a structural spacer to keep the cyclodialysis open. Preferably, the material of the stent can create gaps that allow fluid to flow. The created gaps can run longitudinally along each side of the stent. If the material of the stent is water-permeable, more fluid can pass through the cyclodialysis than when the material of the stent is water-impermeable and the fluid needs to pass along the outside of the stent. Therefore, the materials considered in the present application do not necessarily need to be porous to provide the desired function, but the porosity of the material can improve the function.

[0039] Generally, bioderived stent materials have a certain degree of hardness and intraocular durability such that they can maintain outflow from the anterior chamber, but are inferior in hardness compared to conventional non-bioderived polyimide shunts (e.g., CyPass, Alcon) used in the treatment of glaucoma. The stent material may have a structure sufficient to function as a spacer to open a persistent suprachoroidal outflow as a support bar. The stent material can maintain its structural height or thickness once implanted into the suprachoroidal space so that fluid flow through or around the stent is provided. In some examples, the cut stent is minimally manipulated by compressing or compacting it within the delivery shaft such that the dimensions and / or shape of the cut stent decrease within the shaft from a first dimension to a second, smaller dimension. The delivery shaft can be configured to have dimensions and a shape that allow it to be inserted through the cornea (such as a self-sealing wound of the cornea) into the anterior chamber and advanced towards the iridocorneal angle. The delivery shaft can deploy the compacted stent between tissue layers near the iridocorneal angle. The compacted stent can begin to return to its original shape and / or dimensions once deployed from the delivery shaft. The cut stent can take on a shape and / or dimensions that are smaller than or the same as its original shape and / or dimensions once implanted. Minimally altered biological tissue can be used in the treatment of glaucoma. Bioderived stent materials offer advantages in terms of biocompatibility, anatomical compatibility, and water permeability compared to conventional non-biological materials such as polyimide. Bioderived stent materials provide better compatibility and compliance with the scleral wall, are less likely to cause endothelial and scleral erosion / loss over time, and are less likely to cause chronic eye rubbing and blinking.

[0040] Typically, allogeneic graft tissues for intraocular transplantation are carefully handled so as not to change from their original state. The severed stents described in the present application do not need to be handled so delicately and, instead, can be minimally altered (to about 3.5 mm or less) by compressing or compacting or otherwise wedging into a small space for delivery into the eye from the inside of the eye for intraocular stent formation, occlusion, or reinforcement through an incision or puncture of the cornea or sclera.

[0041] In an example, the material used to form the stent is provided as an uncut patch of material configured to be manually loaded into the cartridge 200. Also, the uncut patch of material can be cut by a cutting assembly independent of the cartridge 200 and then transferred within the region of the cartridge 200. As will be described in more detail below, the cutting can be performed either during the surgery or before the surgery. In a particular example, the stent is formed by 3D printing and can be printed to the desired final dimensions of the stent or printed as a patch of material that will be cut during or before the surgery. The cutting achieved by the devices described in this application can provide thin strips of material that are implanted in the eye to provide regulation of the outflow of water. In the cutting or trephining process, the cut implant can be placed within the conduit or lumen of the cartridge and can be subsequently delivered from the delivery device without the need to remove or transfer the cut implant held within the cartridge. Alternatively, the cutting can be performed independently of transferring the cut implant to the delivery device. The cutting and the transfer of the cut implant to the delivery device can be independent steps performed by separate tools or assemblies. For example, the system can incorporate a first device used to cut the patch of material into the cut implant, a second device used to transfer the cut implant to the delivery device, and a third device used to deploy the cut implant from the delivery device into the eye. It should be understood that the cutting, transfer, and deployment can be integrated into one device or made into separate devices that are used in combination with each other to transfer the patch of material into the cut implant for deployment into the eye. In a preferred embodiment, the cutting and transfer of the cut implant are integrated into the first device and the deployment of the cut implant into the eye is in the second device.

[0042] As used herein, the term "patch of material" refers to a piece of biologically-derived material having dimensions along at least one dimension that are larger than the dimensions of a stent cut from the patch of material and implanted into a patient. In some examples, the patch of material can have a generally square shape, and a stent cut or punched from the patch of material can have a generally rectangular shape. For example, the patch of material can be about 7 mm wide × 7 mm long × 0.55 mm thick, and a stent cut from the patch of material can be 0.3 to 1.0 mm wide × 7 mm long × 0.55 mm thick. The dimensions of the patch of material and the cut stent can vary. The patch of material before cutting can be about 5 mm to about 10 mm wide, about 5 mm to about 10 mm long, and about 0.25 mm to about 2 mm thick. A stent cut from the patch of material can be about 0.3 mm to about 2 mm wide, preferably about 0.7 mm to 1.0 mm wide. A stent cut from the patch of material can be about 5 mm to about 10 mm long. A stent cut from the patch of material can be 0.25 mm to about 2 mm thick. The patch and the cut stent can have the same length and the same thickness, but can also have different widths. Also, the patch material and the stent cut from the patch material can have different lengths and thicknesses. For example, the patch of material can have a first thickness, and a stent cut from the patch of material can have the same thickness, but when implanted, can be folded or rolled to a thickness different from that of the patch of material. The cut stent does not need to be rectangular in shape and can have a non-rectangular shape such as a corner wedge or any of various shapes to provide a particular clinical outcome. For example, a stent cut in the shape of a "dog bone" with enlarged distal and proximal ends can provide additional fixation within the target tissue. The stent can be cut to have an elongated shape at the front end and an enlarged dimension at the rear end to facilitate insertion and to provide at least one end that provides fixation.

[0043] In some examples, the patch of material is of a relatively large width (e.g., 10 mm × 10 mm), and the stent cut from the patch has a much smaller width (e.g., from about 1.0 mm to about 1.5 mm), and the cut stent can be compacted into a delivery conduit having an inner diameter of about 0.8 mm such that the width of the stent substantially fills the inner diameter. The stent can substantially fill the conduit inner diameter even if it is not larger in dimension than the conduit and thus remains uncompacted. The stent is larger in dimension than the inner dimension of the conduit and can be compacted within the conduit to substantially fill it. Further, the dimensions of the cut stent can be varied according to the dimensions of the conduit into which the stent is deployed. For example, the inner diameter of the delivery conduit can be from about 600 microns to about 800 microns. Thus, depending on whether the stent is compacted within the delivery conduit and the inner dimensions of the delivery conduit, the stent can be cut or punched to various dimensions.

[0044] A stent cut from a patch of material can have a width, length, and thickness. In an example, the width of a stent cut from a patch of material using the cutting device described in the present application can be 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 cut from a patch of material can have a width of at least about 100 microns and no more than 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, no more than 800 microns, no more than 700 microns, no more than 600 microns, no more than 500 microns, no more than 400 microns, no more than 300 microns, or no more than 200 microns. The length of the stent cut from the patch of material can be varied according to the implantation site of the stent. In some examples, the stent has a length of 1 mm to 10 mm, more preferably 3 mm to 8 mm. The thickness of a stent cut from a patch of material can be from 100 microns to about 800 microns, or from 150 microns to about 600 microns. In an example, the biological material forming the stent can have a thickness not less than 100 microns and not more than 5 mm. The thickness of the stent can depend on whether the stent is folded or wound during implantation. For example, a patch of material with a thickness of only 250 microns can be cut into a stent and folded during implantation to a thickness of about 500 microns, which is twice the original thickness. Also, the thickness of the stent can depend on what biological-derived material is used. For example, scleral tissue and corneal tissue often have a thickness of about 400 microns, but can shrink to about 250 - 300 microns after collection. Therefore, the thickness of a stent cut from a shrunk patch of corneal tissue can sometimes be only 250 microns.

[0045] In some examples described in more detail below, a stent cut from a patch of material is cut so as to substantially fill the conduit through which it is advanced for delivery. In other examples, the stent can be cut to a graft that is larger than the dimensions of the conduit in which it is deployed. In this example, the stent can be cut to have a first dimension that is larger compared to the inner dimension of the delivery conduit. The larger stent can be primed in the delivery conduit, such as by compressing or compacting it with a tool, so that the stent assumes a second, smaller dimension when primed within the conduit. When deployed in the eye and released from the delivery conduit, the stent can achieve a third dimension that approaches the original first dimension. This will be described in more detail below.

[0046] In non-limiting examples, the biological tissue stent has dimensions of 0.1 mm or more and 8 mm or less in any direction and a thickness of 50 microns or more and 8 mm or less. In non-limiting examples, the stent has a length of about 6 mm, a width of 300 to 600 microns, and a thickness of 150 to 600 microns. The cut can be 1 mm or more and 8 mm or less in any direction. In non-limiting examples, the cut tissue has dimensions of a width of 100 to 800 microns and a length of 1 mm to 10 mm. It should be understood that multiple stents can be delivered to one or more target sites during the transplantation procedure.

[0047] Figures 2 and 6 show an example of the interrelationship of a system 100 for preparing and delivering a biological intraocular stent for increasing water flow and reducing intraocular pressure. The system 100 can include a tissue cartridge 200 having at least a portion configured to be reversibly and operatively coupled to a cutting device 300 and a delivery device 400.

[0048] Each of the systems 100 can include only the tissue cartridge 200 and the delivery device 400 without providing the cutting device 300. In this example, the tissue cartridge 200 can include the pre-cut stent 105 within the cartridge 200 that is ready to engage with the delivery device 400 for intraocular deployment. The cartridge 200 with the pre-cut stent 105 can be immersed in a stabilizing solution. Thus, it should be understood that if the system is described as including the cutting device 300, the cutting device 300 is not used during the surgery. Instead, the stent 105 may be provided in a pre-cut and / or pre-primed configuration within at least a portion of the delivery device 400 or the tissue cartridge 200.

[0049] FIG. 2 shows a first cartridge 200 shown separated from the cutting device 300 and another cartridge 200 installed with the delivery device. The cartridge 200 is configured to receive a patch 101 of material within the cartridge 200 and secure the patch 101 of material in preparation for cutting by the cutting device 300. The cutting device 300, when operating in engagement with the cartridge 200, is configured to form a bio-compatible intraocular stent 105 from the patch 101 of material retained within the cartridge 200. The delivery device 400, when operating in engagement with the cartridge 200, is configured to deliver the cut implant 105 from the cartridge 200 to the implantation site. The tissue cartridge 200 in the example of FIG. 2 is configured to fit with both the cutting device 300 and the delivery device 400 such that the entire tissue cartridge 200 is removed and transferred between the two devices 300, 400 of the system 100.

[0050] FIG. 6 shows an example of the interrelationship of the system 100 and includes a tissue cartridge 200 configured to operate in conjunction with a cutting device 300 and a delivery device 400. However, in order to couple to the delivery device 400, it is not necessary for the entire tissue cartridge 200 to be completely removed from the cutting device 300. In this example, the tissue cartridge 200 can include a distal nose cone assembly 274 configured to decouple from the proximal portion 207 of the cartridge 200 and couple to the delivery device 400. The nose cone assembly 274 can include at least a portion of the distal portion 205, such as a nose cone 275, and a shaft 210 extending distally from the nose cone 275.

[0051] In a further example, the cartridge 200 need not include a portion configured to receive a patch 101 of material within the cartridge 200. For example, the cartridge 200 can include only the nose cone assembly 274 that includes a nose cone 275 having a distal shaft 210. The nose cone 275 having the distal shaft 210 can be coupled to a cutting device 300 configured to receive a patch 101 of material at least within a region and secure the patch 101 of material in preparation for cutting by the cutting device 300. The nose cone 275 and the distal shaft 210 can be positioned relative to the cutting device 300 such that the cut stent can be transferred therein for deployment into the eye. FIG. 14I schematically shows a nose cone assembly 274 coupled to a cutting assembly 500. The nose cone assembly 274 includes a nose cone 275 having a proximal end coupled to the cutting assembly 500 and a distal shaft 210 extending from the nose cone 275 along a longitudinal axis A. The cutting assembly 500 can be a portion of the cutting device 300 described herein.

[0052] The cartridge can include various structural arrangements as described in the present application, but generally refers to a component that can be transferred between two or more devices. The cartridge is transferable between a cutting device and a delivery device. The cartridge can be configured to hold a patch of material for cutting the stent while providing a conduit for deploying the stent into the eye. However, the cartridge need not be configured to hold a patch of material for cutting. The cartridge can include a shaft configured to receive the cut stent from the cutting assembly and then deploy the stent from the shaft into the eye. Any of the various configurations are described and contemplated in the present application.

[0053] These systems and their respective components are described in more detail in the present application.

[0054] Figures 2, 3A - 3C show an example of a tissue cartridge 200 configured to hold a patch of material to provide a conduit for deploying a cut stent into the eye for cutting. The cartridge 200 can include a proximal portion 207 and a distal portion 205 that extends distally therefrom. The distal portion 205 can include an elongate member or shaft 210 having an inner conduit or lumen 238 dimensioned to receive and deploy the stent 105. The proximal portion 207 can include a base 224 and a cover 214 movably attached to the base 224. The proximal portion 207 is intended to remain outside the eye while the distal portion 205 is configured to be inserted into the eye so that the stent 105 can be deployed into the target tissue. The implant 105 can proceed from the proximal portion 207 of the cartridge 200 to deployment located within the distal portion 205 of the cartridge 200. The distal portion 205 of the cartridge 200 can be inserted into the anterior chamber of the eye such that the implant 105 is disposed adjacent to the eye tissue into which the implant 105 is deployed from the cartridge 200. For example, the distal portion 205 of the cartridge 200 can be inserted into the anterior chamber from the inside of the eye through a corneal incision, and the proximal portion 207 of the cartridge 200 remains outside the eye (e.g., attached to the delivery device 400).

[0055] Figures 6, 7A - 7C illustrate another example of a tissue cartridge 200 configured to hold a patch of material for providing a conduit for deploying a severed stent into the eye for cutting. The tissue cartridge 200 can include a proximal portion 207 coupled to a shaft 210 having an internal conduit or lumen 238 (shown in FIG. 14I) sized to receive and deploy a stent 105, and a distal portion 205 extending distally therefrom. The proximal portion 207 can also include a base 224 and a cover 214 movably attached to the base 224. The distal portion 205 and the shaft 210 can be removably attached to the proximal portion 207 of the cartridge 200. For example, the proximal portion 207 can remain within a cutting device 300, and a removable nose cone assembly 274 comprising a nose cone 275 and the shaft 210 can be disengaged from the proximal portion 207 and engaged with a delivery device 400 (see FIGS. 9A - 9D).

[0056] It should be understood that the distal portion 205 of the cartridge 200 can be useful for other delivery routes (e.g., transscleral delivery). Deploying the implant 105 into the eye tissue can include the implant 105 being at least partially present between the ciliary body and the sclera of the eye. The implant 105 can be present between the ciliary body and the sclera within the ciliary body detachment cleft.

[0057] The shaft 210 of the cartridge 200 (also referred to herein as an introducer tube, applicator, conduit, or delivery body) that extends distally outward from the proximal portion 207 of the cartridge 200 includes at least a portion that extends along the longitudinal axis A. At least another portion of the shaft 210 can be angled, curved, or made flexible so as to form a distal bend or flexion away from the longitudinal axis A. In some examples, the shaft 210 can include a flexible portion and a rigid portion such that the shape of the shaft changes according to the relative position of the portions. The examples shown in FIGS. 3A-3C and FIGS. 7A-7C have a proximal portion that extends along the longitudinal axis A and a distal end region 212 that curves downward away from the longitudinal axis A. The distal end region 212 can include an opening 230 from the lumen 238 in which the stent 105 is deployed. The opening 230 from the lumen 238 can be located in a plane perpendicular to the plane of the longitudinal axis A of the distal end region 212 of the shaft 210. The opening 230 from the lumen 238 can be located in a plane that forms an angle with respect to the longitudinal axis A of the distal end region 212 of the shaft 210. The distal end region 212 of the shaft 210 can be beveled such that the opening 230 into the lumen 238 is elongated rather than circular and the most distal tip 216 of the shaft 210 extends beyond the opening 230. The most distal tip 216 of the shaft 210 can be a sharp tip or a blunt tip that does not form a tip. The shape of the opening 230 can be a function of the overall cross-section of the shaft 210 in the distal end region 212 and can be a function of the angle of the opening 230 with respect to the longitudinal axis A of the distal end region 212. For example, when the distal end region 212 of the shaft 210 has a rectangular cross-section and the opening 230 is cut perpendicular to the longitudinal axis A, the shape of the opening 230 and the cross-sectional shape of the shaft 210 substantially coincide. When the shaft 210 has a rectangular cross-section and the opening 230 is cut shorter than perpendicular to the longitudinal axis A, the opening 230 may have an elongated rectangular shape compared to the rectangular shape of the shaft 210.The opening 230 may also have a first shape near the beveled heel and a second shape near the most distal tip 216. For example, the opening 230 near the beveled heel may be rounded and the opening 230 near the most distal tip 216 may be square. It should also be understood that the opening 230 need not be at the most distal end of the shaft 210. The opening 230 can be formed in the sidewall of the shaft 210 such that the stent is biased out of the lumen 238 along a direction having an angle with respect to the longitudinal axis of the lumen 238. The opening 230 can be positioned on the shaft 210 with respect to the cartridge 200 so as to be located at the front end, lower side, upper side, and / or another side of the shaft 210. The distal end region 212 of the shaft 210 can have a cross-sectional shape that is circular, elliptical, rounded rectangular, rounded square, square, diamond-shaped, teardrop-shaped, or other shape, and the most distal tip 216 can have a varying tip shape such as a blunt tip, a bullet tip, a spatula tip, or a pointed tip. The distal end region of the shaft 210 can have any of a variety of configurations known in ophthalmology.

[0058] The shaft 210 can be used to form a cyclodialysis cleft in the suprachoroidal space. The distal end region of the shaft 210 is configured to form a slit and at the same time is configured to provide a conduit for substances to be delivered to the suprachoroidal space of the eye. The shaft 210 can also be used to deliver adhesive substances such as viscoelastic fluids and non-adhesive substances such as scleral tissue. For example, viscoelasticity can be delivered to regions of the eye via the shaft 210 before, during, and / or after stent implantation. A corneal incision can be created using a scalpel or other tool, and the shaft 210 is inserted through the incision, and the distal end of the shaft 210 is navigated to the desired position for delivery. The distal end of the shaft 210 can include a spatula that can be used to separate tissue layers and create a cyclodialysis cleft in the suprachoroidal space between the sclera and the ciliary body. The dimensions, surface finish, and shape of the distal end can minimize trauma. The shaft 210 can further include one or more markers that provide user information regarding the insertion distance. The distal end region of the shaft 210 can include one or more markers for gonimetric criteria regarding how deeply the tongue of the shaft 210 is inserted into the suprachoroidal space. The length of the shaft 210 is sufficient to enable the device to be used from the temporal or superior position.

[0059] The shaft 210 of the cartridge 200 has dimensions and a shape configured to be delivered from the inside of the eye through an incision in the transparent cornea in order to pass the stent 105 through the distal end of the shaft 210. In at least some examples, the distal end region 212 of the shaft 210 is dimensioned to extend through an incision having a length of about 1 mm. In another example, the distal end region 212 of the shaft 210 is dimensioned to extend through an incision having a length of about 2.5 mm or less. In another example, the distal end region 212 of the shaft 210 is dimensioned to extend through an incision having a length between 1.5 mm and 2.85 mm. In some examples, the maximum outer diameter of the shaft 210 is 1.3 mm or less. The most distal tip 216 of the shaft 210 may be blunt or sharp. The blunt most distal tip 216 of the shaft 210 enables dissection between the eye tissues without penetrating or cutting the tissue to place the stent 105. For example, the most distal tip 216 of the shaft 210 can be configured to bluntly dissect between the ciliary body CB and the sclera S (e.g., suprachoroidal space), while the stent 105 remains fully enclosed within the shaft 210 during the blunt dissection. In an alternative example, the most distal tip 216 of the shaft 210 has a sharp cutting configuration for dissecting application and implantation into the subconjunctival space through the scleral wall. In yet another embodiment, the most distal tip 216 can have a cutting configuration for dissection and implantation into Schlemm's canal or transsclerally.

[0060] The shaft 210 is a hypodermic tube of approximately 18G (0.050 inches (") outer diameter, 0.033 inches inner diameter), 20G (0.036 inches outer diameter, 0.023 inches inner diameter), 21G (0.032 inches outer diameter, 0.020 inches inner diameter), 22G (0.028 inches outer diameter, 0.016 inches inner diameter), 23G (0.025 inches outer diameter, 0.013 inches inner diameter), 25G (0.020 inches outer diameter, 0.010 inches inner diameter), 27G (0.016 inches outer diameter, 0.008 inches inner diameter), 30G (0.012 inches outer diameter, 0.006 inches inner diameter) or 32G (0.009 inches outer diameter, 0.004 inches inner diameter). In some examples, the shaft 210 is a hypodermic tube having an inner diameter ranging from less than about 0.036 inches to about 0.009 inches. The system can incorporate a 600 micron shaft 210 or an 800 micron shaft 210. Other dimensions of the shaft 210 are contemplated herein depending on the condition of a particular patient and clinical needs.

[0061] In a preferred example, it should be understood that the stent described in the present application may also include a lumen, but can be formed as a rigid strip of material without a lumen. Therefore, it is generally not possible to move the stent on a guidewire as in a conventional glaucoma shunt. Further, the stent described in the present application can be formed of relatively soft tissue that is more breakable than a typical shunt formed of a harder polymeric or metallic material. A rigid shunt can be implanted using the distal end of the shunt to create a blunt incision at the interface of the tissue into which the shunt is inserted. The stent described in the present application is preferably deployed using a retractable sleeve type injector or introducer that can more gently externalize the stent and retract while remaining accurately positioned once placed in the appropriate anatomical location.

[0062] The dimensions of the shaft 210 can be selected based on the dimensions desired for the stent to be implanted. The stent 105 can have dimensions that substantially fill the lumen 238 of the shaft 210 (or the lumen of at least a portion of the shaft 210 through which it is delivered), and the stent may be urged distally through that portion. In some examples, a stent that substantially fills the lumen is urged distally without wrinkling or damage. In other embodiments, a stent that substantially fills the lumen is urged distally through the shaft 210 to compact the tissue into a plug having a higher density configuration than the stent when cut from the patch. The dimensional difference or gap between the width and height dimensions of the stent 105 and the inner dimensions of the conduit can be up to approximately 200% of the dimensions of the stent 105. The maximum dimension of the conduit is related to the maximum dimension of the stent 105. As an example, if the width of the stent is about 1 mm, the maximum dimension of the conduit is 3 mm, and the total gap between the width of the stent and the outer wall of the conduit is 200% of the stent width. The gap may be less than 5-10% of the maximum dimension of the stent 105. Generally, the smaller the gap between the stent 105 and the conduit, the better the result of advancing the stent 105 through the conduit. If the cross-sectional area of the shaft 210 is greater than 200% of the cross-sectional area of the cut stent 105, the stent 105 may buckle when urged through the shaft 210 and implanted in the eye. The cross-sectional area of the shaft 210 and the cross-sectional area of the stent 105 are preferably substantially dimensionally matched. The conduit can also be coated with a lubricious or low friction material (e.g., Teflon®) to improve the advancement of the stent 105 through the conduit during deployment.

[0063] The cross-sectional area of the shaft 210 can also be smaller than the cross-sectional area of the stent 105. As described above, the stent 105 can be cut to a size larger than the inner diameter of the shaft 210 so that the stent 105 can be compressed, compacted, or otherwise minimally manipulated for delivery through the tube. The stent can be cut to have a first dimension that is larger compared to the inner dimension of the shaft 210. The larger-dimension stent can be primed within the shaft, such as by compacting with a compacting tool 420 so that the stent 105 assumes a second, smaller dimension when primed within the conduit. Upon in-eye deployment and release of the stent 105 from the shaft 210, the stent 105 can achieve a third dimension that approaches its original first dimension. Delivery and deployment will be described in detail below.

[0064] The shaft 210 can be made completely tubular, but it does not necessarily have to be, nor does the cross-section of the shaft 210 have to be circular. For example, the shaft 210 can have a cross-section that is circular, elliptical, square, rectangular, or other shape. Further, the overall length of the shaft 210 does not have to have the same cross-sectional shape or dimensions. For example, the proximal end of the shaft 210 can have a first shape, and the distal end of the shaft 210 can have a second shape. FIGS. 5A-5B show that the cross-section of the shaft 210 is rectangular. The lumen 238 of the shaft 210 does not have to be a completely sealed channel. For example, the shaft 210 can incorporate a wall having one or more openings, apertures, fenestrations, or one or more discontinuities such that the lumen 238 passing through the shaft 210 becomes a partially enclosed channel.

[0065] Referring again to FIGS. 3A - 3C and 7A - 7C. The proximal portion 207 of the cartridge 200 can include a base 224. The distal end region of the base 224 can be coupled to the shaft 210. The proximal end region of the base 224 can include a recess 221 configured to receive a patch 101 of material. The recess 221 can include an inverted V - shaped protrusion 271 projecting upwardly from the centerline of the recess 221 that biases the centerline of the patch 101 of material upwardly while allowing the sides of the patch 101 of material to hang downwardly into corresponding channels 270 on each side of the centerline. FIGS. 7A - 7C show that the proximal portion 207 of the cartridge 200 is reversibly coupled to a nose cone assembly comprising a shaft 210 and a nose cone 274.

[0066] The base 224 is configured to mate with a cover 214 and at least partially surround the recess 221 that contains the patch 101 of material. The cover 214 is configured to engage at least a portion of the patch 101 of material, for example, using a cutting device 300, to stabilize the tissue before and during cutting of the patch 101 of material. In an example, the base 224 can include a slot 215 in the upper surface of the base 224 that is dimensioned and shaped to receive the cover 214. The cover 214 slides through the slot 215 until the lower surface of the cover 214 abuts the receiving surface 218 of the base 224. The contact between the lower surface of the cover 214 and the receiving surface 218 of the base 224 ensures that the centerline of the patch 101 of material in the recess 221 contacts the lower surface of the cover 214 at the protrusion 271 (see FIG. 3C).

[0067] Cover 214 is shown in FIGS. 3A - 3C as a completely removable element from base 224. Cover 214 and base 224 can optionally be joined together by a hinge or other mechanical features. For example, cover 214 can be configured to rotate about the pivot axis of the hinge to expose recess 221 and still remain connected to base 224. FIGS. 7A - 7C show that cover 214 can be toggled between an open configuration and a closed configuration by applying downward pressure to the front end (FIG. 7A) of cover 214 to open cover 214 and applying downward pressure to the rear end (FIG. 7C) of cover 214 to close cover 214. For example, cover 214 can be lifted to an open configuration that exposes recess 221 in base 224 where patch 101 of the material can be located. When cover 214 is in the position to return to the closed configuration, patch 101 of the material can be compressed and / or tensioned between cover 214 and base 224. Cartridge 200 can be inserted into receptacle 306 of cutting device 300 when the cover is in the closed configuration (see FIG. 8).

[0068] Cover 214 (or some other element) can be configured to additionally apply an amount of tension that extends outwardly from the centerline of patch 101 of the material prior to cutting, as described in U.S. Patent No. 10,695,218, issued June 30, 2020, the entire disclosure of which is incorporated herein by reference, to at least a portion of patch 101 of the material.

[0069] Patch 101 of the material can be inserted into cartridge 200 by the user during surgery. Patch 101 of the material may be provided in dimensions approximating the dimensions of recess 221 within base 224. The user may trim patch 101 of the material prior to placing it in recess 221. Alternatively, cartridge 200 can be provided pre - loaded with patch 101 of the material located within the recess.

[0070] As described elsewhere in this application, the cartridge need not be configured to hold the patch of material 101 for cutting by the cutting device 300. Rather, the cutting device 300 can be configured to hold the patch of material 101 for cutting and transfer the cut stent to the cartridge coupled to the cutting device 300. FIGS. 10A-10C illustrate an example of a cartridge 200 that forms a nose cone 274 having a shaft 210 loaded with a stent cut prior to insertion into the eye. The nose cone 274 can be reversibly coupled to the cutting device 300 and, when loaded with the cut stent, removed from the cutting device 300 and coupled to the delivery device 400. The cartridge 200 can be positioned relative to a cutting device 300 configured to hold the patch of material 101 and cut it into the stent 105. The connection between the cutting device 300 and the cartridge 200 can align the longitudinal axis of the distal shaft 210 with respect to the region of the cutting device such that the cut stent 105 is transferred into the distal shaft 210 using a rod or other tool described in more detail below. The cartridge 200 having the distal shaft 210 with the stent 105 located therein can be decoupled from the cutting device 300 and transferred to a portion of the delivery device 400. The cartridge 200 need not include a portion configured to hold the patch of material 101 for cutting and instead can include a transportable portion that can be alternately coupled to the region of the cutting device 300 and the region of the delivery device 400. This will be described in more detail later.

[0071] Figures 4A - 4J and 8 illustrate an example of a cutting device 300 having a cutting assembly for cutting a stent from a patch of material 101. Figures 14A - 14H illustrate various examples of a cutting assembly 500 that can be incorporated into the cutting device 300. The cutting device 300 is configured to cut or otherwise prepare a biologically derived tissue or patch of material 101 having a first contour or shape (e.g., a wide square sheet or patch of material) into a second contour or shape (e.g., an elongated rectangular strip of material) that conforms to a transplantable stent 105 having the dimensions described herein. The cutting performed using the cutting device 300 described herein can involve guillotine, punch, rotational, sliding, rolling, or pivoting blade cutting operations. In some examples, the cutting is performed orthogonal to the plane of the patch of material. In some instances, the cutting is performed axially along a transplant conduit such that the axis of the cutting is positioned inside or parallel to the transplant conduit to enable unobstructed loading and transfer of tissue for transplantation without manipulating, tearing, or damaging the delicate stent tissue.

[0072] As described above, prior to the cutting step there is a tissue fixation step in which the biologically derived tissue forming the stent is firmly fixed between two mating planes such that subsequent cutting results in accurate dimensions without the tissue becoming wrinkled or deformed. Fixation can optionally provide tension or stretch, in addition to compression of the tissue, in at least one plane to cleanly cut the tissue. The cutting assembly 500 can hold the patch of material 101 prior to cutting or the patch of material 101 can be held within the region of the tissue cartridge 200 prior to cutting by the cutting assembly 500. In some examples, the cutting device 300 in combination with the cover 214 of the cartridge 200 can incorporate front - to - back capture such that the patch of material 101 to be cut is fixed in the z - plane preventing movement prior to engaging the tissue with the cutting member 312.

[0073] Cutting can be performed inside a path or conduit formed within the cartridge 200. The graft 105 cut from the patch 101 of the substance can be simultaneously or subsequently placed within the delivery conduit or the delivery conduit and the graft 105 can be aligned such that the cut graft 105 is delivered to the eye through the conduit without the need for the cut graft 105 to be transferred from the cartridge 200.

[0074] As an example, the patch 101 of the substance held within the recess 221 of the cartridge 200 is distally biased from the recess 221 into the lumen 238 of the shaft 210 of the cartridge 200 and is cut by a cutting member 312 of a cutting device 300 that forms a stent 105 cut within the recess 221 of the cartridge 200 that can be fully deployed into the eye without removing the stent 105 cut from the cartridge 200 or at least the distal portion 205 of the cartridge 200.

[0075] With respect to FIGS. 4A-4B and 6, the cutting device 300 can include a base 302 having a distal portion 305 and a proximal portion 307. The distal portion 305 can include a distal opening or receptacle 306 that is sized and shaped to receive the proximal portion 207 of the cartridge 200. The inner diameter of the receptacle 306 can be made sufficient to receive the outer diameter dimension of the proximal portion 207 such that the proximal portion 207 is inserted into the receptacle 306 at a distance. The cover 214 of the cartridge 200 is positioned within the slot 215 to maintain the patch 101 of the substance within the recess 221. The upper surface of the cover 214 can extend above the upper surface of the base 224 such that the outer profile dimension of the proximal portion 207 is keyed. In other words, the outer profile dimensions of the cartridge 200 are keyed and can only be inserted into the receptacle 306 of the cutting device 300 in a single orientation (e.g., the cover 214 positioned on the upper side).

[0076] The cutting device 300 can additionally include a cutting assembly 500 having a cutting member 312 configured to cut a patch 101 of material within the recess 221 of the cartridge into the stent 105 (see FIG. 4C). The configuration of the cutting member 312 can be varied. In this configuration, the cutting member 312 can include at least a first blade 344a and a second blade 344b spaced apart from the first blade 344a. The first and second blades 344a, 344b can be positioned over the patch 101 of material when the cartridge 200 is installed within the receptacle 306 of the cutting device 300. Upon actuation of the cutting member 312, the first and second blades 344a, 344b are biased toward the patch 101 of material, thereby cutting through the thickness forming the stent 105. The blades 344a, 344b can have a width along the longitudinal axis A of the cartridge 200 sufficient to cut the entire length of the patch 101 of material. The distance between the blades 344a, 344b can be configured to achieve a desired width for the cut stent 105.

[0077] In some examples, the blades 344a, 344b can be positioned above the patch 101 of material to be cut, and corresponding lower blades 345a, 345b can be positioned below the patch 101 of material. Thus, when the blades 344a, 344b are biased downwardly toward the patch 101 of material, the patch 101 of material is biased toward the lower blades 345a, 345b such that the corresponding upper and lower blades completely cut the patch 101 of material at two locations to form the stent 105.

[0078] The cutting member 312 can be actuated by a user to move the blade. The cutting device 300 can include one or more handles 343 movably coupled to the base 302 to actuate the cutting member 312. The handle 343 can be coupled by a hinge 317 such that the handle 343 rotates about the pivot axis P of the hinge 317 relative to the base 302. For example, the handle 343 can be lifted to pivot to an open configuration as shown in FIG. 4A and rotated back about the pivot axis P to a cutting configuration as shown in FIG. 4B.

[0079] The cartridge 200 may be inserted into the receptacle 306 of the cutting device 300 when the handle 343 is lifted to an open configuration and the cutting member 312 is in a position away from the cutting configuration. As best shown in FIGS. 4D-4E, the cartridge 200 may be slid into the receptacle 306 such that the recess 221 holding the patch 101 of material is positioned below the upper blades 344a, 344b and above the lower blades 345a, 345b. The cover 214 that holds the patch 101 of material in the recess 221 may include an upper portion 220 that tapers to a narrower lower portion 222. The lower portion 222 of the cover 214 is aligned with the protrusion 271 of the recess 221 and sandwiches the patch 101 of material therebetween. The upper portion 220 of the cover 214 may slide above the upper blades 344a, 344b when the cartridge 200 is attached to the cutting device 300. The lower portion 222 of the cover 214 is dimensioned to slide between the upper blades 344a, 344b when the cartridge 200 is inserted into the receptacle 306 of the cutting device 300. FIG. 4D shows the upper blades 344a, 344b spaced apart from the lower blades 345a, 345b with the narrow lower portion 222 of the cover 214 positioned therebetween. FIG. 4E shows the handle 343 rotated back to the cutting configuration with the upper blades 344a, 344b biased downwardly toward the patch 101 of material and toward the lower blades 345a, 345. The patch 101 of material is cut by corresponding upper and lower blades that form the stent 105. The width of the stent 105 cut from the patch 101 of material is determined by the distance between the upper and lower blades.

[0080] The handle 343 can open along any one of several directions relative to the base 302. For example, the pivot axis P of the hinge 317 can be substantially orthogonal to the longitudinal axis A of the base. In this example, the hinge 317 can be positioned at the distal end of the base 302 such that the handle 343 rotates upwardly and hinges open toward the distal end of the base 302. The upper blades 344a, 344b may be spring-loaded so as to easily return to the open configuration when the handle 343 is lifted or released.

[0081] Once cut, the stent 105 is received on all sides by the cartridge 200 and the cutting member 312, forming a complete enclosure or stent cutting chamber for the stent 105 within the assembly of the cutting device 300 and the cartridge 200. For example, the floor and ceiling of the stent cutting chamber can be formed by the lower portion 222 of the cover 214 and the protrusion 271 of the recess 221. The walls of the stent cutting chamber can be formed by the upper blades 344a, 344b and the lower blades 345a, 345b of the cutting member 312. Together, the walls of the stent cutting chamber can form a rectangle to help constrain and direct the pusher 320 of the cutting device 300 as it advances to press the stent 105 distally from the stent cutting chamber into the lumen 238 of the shaft 210. In an example, the stent cutting chamber can have at least a partially arcuate or circular cross-section. The upper and lower surfaces of the cutting chamber can be curved or non-planar. As an example, the lower portion 222 of the cover 214 can form a recess that forms an arcuate ceiling for the cutting chamber. The floor of the cutting chamber formed by the protrusion 271 may incorporate a corresponding indentation. The arcuate ceiling and indented floor of the cutting chamber reduce the amount of open space that occurs around the cut stent 105 relative to the inner wall of the shaft, which would otherwise allow the push rod to go off track or the cut stent 105 during deployment to deviate from the desired path. Minimizing the void within the shaft for the treffing stent 105 improves the advancement of the stent 105 within the device. The cut stent 105 can then have a cross-sectional shape that closely conforms to the cross-sectional shape of the delivery conduit through which the stent 105 must advance. With the corresponding shape, the extra space above and below the cut stent 105 relative to the conduit can be eliminated. This provides better guidance for the pusher 320 for advancing the cut stent 105 toward the distal end of the shaft. The stent 105 can also be cut to be larger relative to the conduit and can be compressed, compacted or otherwise manipulated within the conduit prior to deployment, as described elsewhere in this application.

[0082] Once cut, the stent 105 can be axially aligned with the lumen 238 of the shaft 210 of the cartridge 200. FIGS. 4F-4G and FIGS. 4H-4J show that the cutting device 300 can include a pusher 320 configured to slide distally relative to the base 302 within the proximal end region of the cartridge 200 and advance the cut stent 105 from this fully enclosed position along the delivery catheter into the lumen 238 of the shaft 210. In the example of FIG. 6, the pusher 320 is not visible. However, the base 302 can include an actuator 304, such as a dial, button, slider, or other input means, that is coupled to and operates to move the pusher 320 distally relative to the base 302 during operation. Any of a variety of user actuators 304 are contemplated herein for moving the pusher 320 to prime the stent 105 to a predetermined position relative to the lumen 238. This priming step by the pusher 320 of the cutting device 300 ensures that the cut stent 105 is retained within the fully enclosed space on all sides (i.e., the region of the shaft 210) after removing the cartridge 200 from the cutting device 300 and before coupling the cartridge 200 with the delivery device 400.

[0083] FIG. 4H shows that while the handle 343 is biased downward toward the base 302 (e.g., the blade 344 is in a cutting configuration relative to the implant 105), the pusher 320 of the cutting device 300 can advance distally through the base 302. FIG. 4I shows that the pusher 320 is ready to engage the stent 105 within the proximal recess 221. FIG. 4J shows that the pusher 320 advances the stent 105 distally within the lumen 238 of the shaft 210 of the cartridge 200. As described above, the side blade 344, the upper cover 214, and the lower protrusion 271 create a complete enclosure for the cut stent 105 on all sides, preventing the stent 105 from buckling within the lumen 238 during this distal advancement. The conduit in which the stent 105 is held is sized (or sized smaller) to fit the outer dimensions of the stent to be implanted, thereby preventing buckling and wrinkling when the stent 105 is biased to its primed position.

[0084] The stent 105 is biased to the distal end region 212 of the shaft 210, and the cartridge 200 can be removed from the cutting device 300. When the cutting device 300 and the cartridge 200 are disengaged from each other, the cartridge 200 is ready to load the delivery device 400 for inserting the stent 105 into the eye.

[0085] The patch of material 101 can be cut and loaded into the shaft 210 of the cartridge 200 in various ways. As discussed elsewhere, the patch of material 101 can be cut to substantially the same dimensions as the conduit through which it is delivered. The patch of material 101 can preferably be cut to dimensions slightly larger than the lumen dimensions such that the stent 105 is compressed and delivered and is compressed within the lumen such that the stent 105 can more easily proceed through the lumen 238. The cutting can be performed as described above with respect to FIGS. 4A-4E. The cutting of the patch of material and its transfer to the shaft 210 can also be performed using other cutting assemblies 500 as described below and as described with respect to FIGS. 14A-14H. The cutting assembly 500 described in the present application can form part of the tissue cartridge 200, the cutting device 300, or the delivery device 400. Preferably, the cutting assembly 500 is part of the cutting device 300. The cutting device 300 can be coupled to at least a portion of the cartridge 200, such as a nose cone assembly 274 having a distal shaft 210 extending from the nose cone 275, such that the cut stent 105 can be primed within the shaft 210 for delivery using the delivery device 400. The cartridge 200 can include a removable nose cone 274 and a proximal portion 207 configured to hold the shaft 210, not including a proximal portion 207 for holding the patch of material for cutting as shown in FIGS. 2, 3A-3C, or 7A-7C, or for holding the patch of material as shown in FIGS. 9A-9D, 10A. The cartridge 200 can be a transferable component configured to couple to the cutting assembly, prime and remove the cut stent from the cutting assembly, and couple to a delivery device for deploying the cut stent into the eye, whether or not it is configured to hold the patch of material for cutting.

[0086] FIG. 14A shows an embodiment of the cutting assembly 500. The cutting assembly can be part of a cutting device 300 configured to engage a cartridge. The cutting assembly 500 can cut a patch 101 of material, which can be held within the cartridge or within the region of the cutting assembly 500. The cut stent can be transferred from the cutting assembly 500 into the distal shaft 210 of the cartridge 200 for delivery into the eye through the shaft. The cutting assembly 500 can incorporate a cutting die 511 disposed relative to a slot 507 in a base 509 and a movable member 505 having a planar cutting surface 513 coupled to the base 509. The movable member 505 can be pivoted 90 degrees relative to the base 509 from a first position to a second position. When the movable member 505 is pivoted to its second position, the patch 101 of material can be disposed relative to the cutting surface 513. The cutting die 511 can compress the patch 101 of material against the cutting surface 513. Advancing the cutting die 511 toward the cutting surface 513 can cut the patch 101 of material at two locations, as described elsewhere in this application. Excess tissue is removed from the cutting surface 513, and the movable member 505, which still holds the cut stent 105 on its cutting surface 513, can be pivoted back toward the first position. Thereby, the cut stent 105 on the cutting surface 513 is positioned within the path of the slot 507 such that a compacting tool 517 or other member can load the cut stent 105 into the slot 507. The slot 507 can have a terminal region 508 that positions it along the longitudinal axis A of the distal shaft 210 when the cartridge 200 is coupled to the cutting device 300. The terminal region 508 can have a rounded cross-sectional shape similar to the cross-sectional shape of the distal shaft 210. The cut stent 105 positioned within the terminal region 508 can be biased into the lumen of the distal shaft 210 to be primed for delivery.The dimensions of the slot 507 and / or the end region 508 can be made smaller than the dimensions of the cut stent 105 such that the cut stent 105 is compressed and compacted into a plug by the advancement of the compacting tool 517 that biases the cut stent 105 into the slot 507. When the cut stent 105 is positioned within the distal shaft 210 of the cartridge 200, the cartridge 200 can be removed from the cutting device 300 and transferred to the delivery device 400 for deployment within the eye.

[0087] FIG. 14B shows an interrelated example of a cutting assembly 500 for cutting a patch 101 of material and transferring the cut stent 105 for delivery. Similar to the embodiment of FIG. 14A, the cutting assembly 500 can be part of a cutting device 300 configured to engage a cartridge. The patch of material can be held within the region of the cartridge for cutting or can be held by a portion of the cutting assembly 500. The cutting die 511 can be inserted through the compression pad 515 to cut the patch 101 of material. The patch 101 of material can be positioned relative to the cutting surface 513. The cutting surface 513 need not be part of a movable member as in the previous example and can be at least part of the base 509. The patch 101 of material can be compressed between the cutting surface 513 of the base 509 and the compression pad 515. The cutting die 511 can advance through the compression pad 515 such that the blade of the cutting die 511 cuts the patch 101 of material in two places. After the patch 101 of material is cut, excess tissue can be removed and the pressure applied by the compression pad 515 can be released. The cutting die 511 can include a spring 516 such that it returns to its initial position and the compression pad 515 and the cutting die 511 no longer apply pressure to the cut stent 105. The cut stent 105 can be positioned relative to the slot 507 of the base 509 such that a compacting tool 517 can urge the cut stent 105 toward the distal region 508 through the slot 507. As described elsewhere, the cut stent 105 can be sized larger relative to the dimensions of the slot 507 to compact the stent 105 for delivery by urging the stent into a conduit. The slot 507 can have a distal region 508 that aligns with the longitudinal axis A of the distal shaft 210 when the cartridge is coupled to the cutting device 300. The cut stent 105 positioned within the distal region 508 can be urged against the distal shaft 210 to be primed for delivery.A cartridge containing the severed stent 105 can be removed from the cutting device 300 and transferred to a delivery device 400 for deployment within the eye.

[0088] FIG. 14C shows an exemplary interrelationship of a cutting assembly 500 for cutting a patch 101 of material and transferring the severed stent 105 for delivery. The cutting assembly 500 can further incorporate a movable stop 520 positioned between the patch 101 of material and a slot 507 through which the severed stent 105 proceeds. A compression pad 515 and a cutting die 511 can compress the patch 101 of material against a cutting surface 513 of a base 509. The patch 101 of material can be enclosed between the lower cutting surface 513, the distal movable stop 520, and the upper compression pad 515. The cutting die 511 can include a single blade and can advance through the compressed patch 101 of material to cut the patch at a single location to create the stent 105. The cutting die 511, the compression pad 515, and the movable stop 520 can retract away from the severed stent 105 such that a compacting tool 517 can distally bias the severed stent 105 into the slot 507 for delivery. A terminal region 508 of the slot 507 can be aligned with a longitudinal axis A of a distal shaft 210 when the cartridge is coupled to the cutting device 300. The severed stent 105 positioned within the terminal region 508 can be biased within the distal shaft 210 to be primed for delivery as described elsewhere. FIG. 14I shows a nose cone assembly 274 positioned relative to the cutting assembly 500 of FIG. 14C. The longitudinal axis A of the distal shaft 210 of the nose cone assembly 274 can be aligned with the terminal region 508 of the slot 507 such that the compacting tool 517 can bias the severed stent 105 into the shaft 210. When the severed stent 105 is compacted into the lumen 238 of the shaft 210, the nose cone assembly 274 can be removed from cooperation with the cutting assembly 500 and transferred to a delivery device 400 for deployment within the eye.

[0089] The position of the movable stop 520 relative to the cutting blade of the cutting die 511 can be adjusted to achieve different stent widths. For example, the movable stop 520 can move towards a single blade of the cutting die 511 to reduce the width of the stent and move away from the cutting die 511 to increase the width of the stent. The position of the movable stop 520 relative to the cutting die 511 can be selected by the user, for example, via a dial or other user interface that allows for incremental adjustment. The range of the dial can be from about 0.6 mm to about 1.9 mm and can include markings laid out per 1 / 4 to 1 / 16 threads. The cutting die 511 of the cutting assembly 500 can be attached to a lever, handle, or other actuator 343 as described elsewhere in the present application to advance a single blade through a patch 101 of material held against the cutting surface 513 by the pad 515 when selecting the width. In an example, the cutting surface 513 can be 1 / 16 inch (") 90A silicone.

[0090] Figures 15A - 15B show a cutting device 300 having a cutting assembly 500. The cutting device 300 can include a handle 543 movably coupled to a base 509 to operate the cutting assembly 500. For example, the handle 543 is configured to raise and lower a cutting die 511 relative to a cutting surface 513 of the base 509. The cutting surface 513 can include a recess 544 dimensioned to hold a patch of material (not shown). The cutting surface 513 can be made movable relative to the base 509 to expose the recess 544 for placing a patch of material 101 within the recess 544. The cutting device 300 can incorporate an actuator 545 such as a dial, button, slider, switch, or other type of actuator configured to adjust the position of the cutting die 511 relative to the cutting surface 513 as described above. The actuator 545 can move the base 509 left and right via a screw or other mechanism to change the position of the patch of material 101 held within the recess 544 relative to the cutting die 511, thereby changing the width of the stent cut from the patch. Alternatively, the actuator 545 can move the cutting die 511 relative to the recess 544 to change the width of the stent. The cutting device 300 can incorporate a stage 546 configured to be movable relative to the base 509, such as by sliding, pivoting, or lifting away from the base 509. In some examples, the stage 546 can slide in a single plane relative to the underlying base 509 while remaining at least partially connected to the base 509. Alternatively, the stage 546 can be completely removed from the base 509. Moving the stage 546 relative to the base 509 can expose the recess 544 from beneath the area of the device where the cutting die 511 and handle 543 are located. This allows for loading of the patch into the recess 544 without the components of the cutting assembly 500 obstructing the user's view or physical access. The cutting device 300 can be a solo cutter and does not need to incorporate a compression mechanism, a holding mechanism, or a conveyance mechanism.Rather, the severed stent 105 following cutting at the cutting assembly 500 can be manually transferred to another tool for priming the severed stent 105 for deployment through the shaft.

[0091] FIG. 14D shows an exemplary interrelationship of a cutting assembly 500 for cutting a patch 101 of material. The cutting assembly 500 can include a cutting such as a paper punch. A sharp corner or raised sharp edge 525 can project from the cutting surface 513. The sharp edge 525 can surround the hole 527 through the cutting surface 513 that directly connects to the slot 507 in the base 509. The patch 101 of material can be positioned against the cutting surface 513 over the hole 527 and against the sharp edge 525. The punch 511 can be biased against the patch 101 of material from above such that the patch 101 of material is cut by the sharp edge 525 and the severed stent 105 is biased through the hole 527 by the punch 511 into the slot 507. The severed stent 105 can be placed within the slot 507 such that a pusher (not shown in FIG. 14D) biases the severed stent 105 through the slot 507 toward the distal end region 508. The distal end region 508 of the slot 507 aligns the severed stent 105 with the longitudinal axis A of the distal shaft 210 such that the stent is biased into the distal shaft 210 and primed for delivery. The cartridge can be removed from the cutting device 300 and transferred to the delivery device 400 for deployment within the eye.

[0092] FIG. 14E shows an example of an interrelated cutting assembly 500 for cutting a patch 101 of material. The cutting assembly 500 can also incorporate a cutting like a money plunger. The patch 101 of material is positioned over a slot 507 in a base 509 such that a cutting die 511 can be biased downwardly against the patch 101 of material so that the cutting edge of the cutting die 511 can cut the patch 101 of material at two locations to cut the stent 105 to length. A compacting tool 517 can advance through a bore 529 in the cutting die 511 to drive the cut stent 105 into the slot 507 that biases the distal end region 508 of the slot 507. The compacting tool 517 or an additional compacting tool 421 can compress the stent 105 cut within the distal end region 508 of the slot 507 and align the cut stent 105 with the distal shaft 210 and can proceed through the bore 529 in the cutting die 511 to be primed for delivery. The cartridge can be removed from the cutting device 300 and transferred to a delivery device 400 for deployment within the eye.

[0093] FIG. 14F shows an example of an interrelated cutting assembly 500 for cutting a patch 101 of material. The cutting assembly 500 can incorporate a forceps-like tool 530 for clamping the patch 101 of material. A scalpel or other cutting tool 535 can be used to trim the patch 101 of material held by the forceps 530 to length. The forceps 530 holding the cut stent 105 are positioned relative to the base 509 and the clamping pressure of the forceps 530 is released. A compacting tool 517 can proceed through the forceps 530 to bias the cut stent 105 from the forceps 530 into the slot 507 in the base 509 to compress and compact the cut stent 105 for delivery as described above.

[0094] FIG. 14G shows an example of an interrelated cutting assembly 500 for cutting a patch 101 of material. The cutting assembly 500 can incorporate a plunger configured to compress the patch 101 of material within a transfer slot 537 of a transfer base 539. The patch 101 of material can be trimmed to size using a scalpel or other cutting tool 535. The cut stent 105 within the transfer slot 537 can be transferred by aligning the transfer slot 537 with a slot 507 of a base 509 having a predetermined slot 507 and attaching the transfer base 539 to the base 509 in a manner that compresses and loads the cut stent 105 within the transfer slot 537 for deployment using a compacting tool 517.

[0095] FIG. 14H shows an example of an interrelated cutting assembly 500 for cutting a patch 101 of material. The cutting assembly 500 can incorporate a rotating cylinder 540 configured to cut and dispose of the cut stent 105 relative to a slot 507 of a base 509 for loading and compressing the stent 105 for delivery. The rotating cylinder 540 can incorporate an internal slot 542 for receiving at least a portion of the patch 101 of material. Rotation of the cylinder 540 trims excess tissue extending beyond the slot 542 of the cylinder 540. The cut stent 105 trimmed to length within the slot 542 of the cylinder 540 is disposed relative to the slot 507 of the base 509 for loading and compression for delivery.

[0096] The cut stent 105 loaded and compressed for delivery can be positioned within at least a portion of a cartridge 200, such as within a lumen 238 of a shaft 210. At least a portion of the cartridge 200 can be removed from the cutting device 300 and engaged with a delivery device 400 for deployment of the stent 105 from the cartridge 200 into the eye. The compression and transfer of the cut stent 105 described above in relation to the cutting assembly 500 prepares the cut stent 105 for delivery without removing the cut stent 105 from the cartridge 200.

[0097] Cartridge 200 is described herein as being configured to couple to a cutting device 300 having a cutting assembly 500 for cutting a patch 101 of material and then to be removed from engagement with the cutting device 300 so as to be coupleable to a delivery device 400. This relationship can include removing and reengaging the entire cartridge 200 or only a portion of the cartridge 200, for example, only the nose cone assembly 274 (e.g., nose cone 275 and shaft 210). Herein, both are considered. The nose cone assembly 274 may simply be referred to herein as the cartridge 200. When the cartridge 200 is described as being removed from the cutting device 300, that description relates to either only the nose cone assembly 274 being removed or the entire cartridge 200 being removed from the cutting device 300. When the cartridge 200 is described as being configured to engage the delivery device 400, that description relates to either only the nose cone assembly 274 engaging or the entire cartridge 200 engaging the delivery device 400. Each instance of coupling between the cartridge 200 and another component of the system 100 may be the entire cartridge 200 or only a portion of the cartridge 200, such as the nose cone assembly 274.

[0098] The patch of material 101 can be disposed within a portion of the cartridge 200 for cutting, or the patch of material 101 can be disposed within a portion of the cutting device 300 for cutting by the cutting assembly 500, and the cut stent 105 can be transferred to the cartridge 200 (or only a portion of the cartridge 200 such as the nose cone assembly 274). The cut stent 105 is transferred to the cartridge 200 using components of the cutting assembly 500 and separated from the cutting device for coupling to the delivery device. The patch of material 101 is located within the region of the cutting assembly 500 for cutting, and the cut stent 105 can be manually transferred from the cutting assembly 500 for compacting within the delivery shaft 210. The cut stent 105 can be transferred using a device separate from the cutting assembly 500, including manually. In an example, the system includes a cutting device 300 having a cutting assembly 500. The cut stent 105 from the cutting assembly 500 can be manually transferred (e.g., with forceps) to a transfer device having a compaction tool 517 for compacting the cut stent 105 into the distal shaft 210. The distal shaft 210 having the cut stent 105 compacted therein can be coupled to the delivery device 400 for deploying the cut stent 105 into the eye. The system can have separate devices for the cutting device, the transfer device, and the delivery device, rather than having one or more devices integrated. The cutting assembly 500 shown in FIGS. 14A - 14H can be part of the cutting device. The transfer element of the cutting assembly 500 can be integrated with the cutting device or can be a separate transfer device.

[0099] System 100 can include a delivery device 400 configured to couple to at least a portion of a cartridge 200 that holds a cut stent 105. In some examples, the entire cartridge 200 having the cut stent 105 is removed from the cutting device 300 and engaged with the delivery device 400 (see FIG. 2). In related examples, a portion of the cartridge 200 having the cut stent 105 located therein is removed from the cutting device 300 and engaged with the delivery device 400 (see FIGS. 6, 9A-9D).

[0100] In the examples shown in FIGS. 5A-5B, the cartridge 200 that holds the cut stent 105 can be removed and loaded into the delivery device 400. FIGS. 5C-5F show the loading of the tissue cartridge 200 into the delivery device 400 and the deployment of the cut stent 105 using the delivery device 400. Together, the cartridge 200 and the delivery device 400 can be used to deliver the stent 105 to the implantation site, such as via a delivery path from inside the eye (ab intero). Thereby, it is not necessary to remove the cut stent 105 from its location within the cartridge 200 in order to load the cut stent 105 into the delivery device 400, and the stent can be loaded and deployed. At least a portion of the cartridge 200 (e.g., the proximal portion 207 of the cartridge 200 or the region of the nose cone assembly 274) is held by the delivery device 400, and the distal portion 205 of the cartridge 200 can be inserted into the eye.

[0101] The delivery device 400 can include a proximal handle 405 sized and shaped to be grasped by a user's single hand, and a distal end region 410 defining a mounting mechanism 425 such as a receptacle 412 sized to engage at least a portion of the cartridge 200. In an example, the receptacle 412 can be sized to receive at least a certain length of the proximal portion 207 of the cartridge 200 (see FIG. 5C). In an example of interrelation, the mounting mechanism 425 can incorporate another male-female mounting mechanism such as a bayonet connector 413 (see FIGS. 10A-10C). As described above with respect to the cutting device 300, the mounting mechanism 425 can be keyed so that the cartridge 200 with the cover 214 in a predetermined position on the base 224 can be received within the mounting mechanism 425 or otherwise engaged in a single orientation. When the cartridge 200 is coupled to the mounting mechanism 425 of the handle 405, the shaft 210 of the cartridge 200 extends distally outwardly from the handle 405. The keying function of the mounting mechanism 425 can prevent attachment in the wrong direction. The mounting mechanism 425 can provide a secure connection by indicating tactile feedback to the user when the connection is fully engaged. The mounting mechanism 425 is also sized to ensure alignment of the lumen 238 of the shaft 210 with an internal mechanism of the delivery device 400 such as a push rod 420.

[0102] The attachment mechanism 425 of FIGS. 5A - 5C can have a receptacle 412 deep enough to include a length of the proximal portion 207 of the cartridge 200 while the shaft 210 remains outside the receptacle 412. The flexible hook 422 can extend into at least a portion of the receptacle 412 (see FIG. 5C). The distal end 424 of the hook 422 can be received within a detent 272 configured in a corresponding shape near the proximal end region of the tissue cartridge 200. As the cartridge 200 slides within the receptacle 412, the distal end 424 of the hook 422 can slide through the proximal portion 207 of the cartridge 200 and be inserted into the detent 272. The flexibility of the hook 422 biases it upward as the distal end 424 of the hook 422 travels through a first region of the cartridge 200 and then flexes downward and back as the distal end 424 travels further, thereby enabling engagement of the detent 272 (see FIG. 5D). The spring - loaded hook 422 that engages the detent 272 can provide a tactile and / or audible "click" to inform the user that the cartridge 200 is fully installed and held within the delivery device 400 and ready for stent 105 delivery.

[0103] One or more actuators 415 can be located in a region of the handle 405. The actuator 415 can also be operated with one hand of the user, such as with the thumb or another finger. The configuration of the actuator 415 can be varied. For example, the actuator 415 can include any of a variety of knobs, buttons, sliders, dials, or other types of actuators configured to move one or more components of the delivery device 400, as will be described in more detail below.

[0104] The delivery device 400 can include a compacting tool 420 configured to be moved by one or more actuators 415. When the distal end of the shaft 210 reaches a desired position, the compacting tool 420 can be used with the cartridge 200 to deliver the stent 105 from the cartridge 200. The compacting tool 420 can be configured with dimensions and a shape complementary to the inner dimensions of the shaft 210. For example, if the shaft 210 of the cartridge 200 has a rectangular cross-sectional shape, the compacting tool 420 may have a rectangular cross-section. Thereby, the compacting tool 420 can effectively urge the stent 105 cut through the lumen 238 of the shaft 210.

[0105] The compacting tool 420 can be fully retracted to a proximal position before coupling the tissue cartridge 200 within the delivery device 400, such that the compacting tool 420 does not interfere with the loading of the cartridge 200. As shown in FIGS. 5D and 9B, when the cartridge 200 is installed and held within the delivery device 400, the compacting tool 420 can advance distally through the proximal port of the cartridge 200 and into the lumen 238 of the shaft 210 (see FIGS. 5E and 9C). In some examples, the compacting tool 420 can advance through the lumen 238 and out of the distal opening 230 of the lumen 238 to deploy the stent 105. In other examples, the compacting tool 420 advances to a distal position near the proximal end of the stent 105 within the lumen 238, and the shaft 210 retracts proximally while the compacting tool 420 remains stationary to deploy the stent 105 (see FIGS. 5F and 9D).

[0106] The shaft 210 can be retracted proximally via movement of the cartridge 200 in a proximal direction relative to the delivery device 400 while the compacting tool 420 remains stationary, in order to deploy the stent 105 into the eye (see FIGS. 5F and 9D). Thus, the compacting tool 420 can thereby act as a stopper to prevent the stent 105 from following the shaft 210 as the shaft 210 retracts. As a result, the stent 105 is unsheathed from the shaft 210 and left within the tissue. In other examples, both the cartridge 200 and the compacting tool 420 are movable to effectively deploy the stent from the shaft 210.

[0107] In some examples, the compacting tool 420 can be coupled to the first actuator 415, and the cartridge 200 can be coupled to the second actuator 415. The first and second actuators 415 can be sliders, buttons, or other configured or combined actuators configured to advance and retract their respective components. The first actuator 415 coupled to the compacting tool 420 can retract proximally such that the compacting tool 420 is in its closest position when the cartridge 200 is engaged by the attachment mechanism 425 of the delivery device 400. The user can advance the first actuator 415 to bias the compacting tool 420 distally to advance the stent 105 within the lumen 238 of the cartridge 200 toward the distal opening 230 of the shaft 210. After the cut stent 105 is primed in its distal position within the lumen 238, the shaft 210 of the cartridge 200 can be used to dissect the eye tissue until the target location is accessed. When the shaft 210 is in a predetermined position to deploy the stent 105 into the eye, the first actuator 415 coupled to the compacting tool 420 is maintained in this distal position, and the second actuator 415 is actuated (e.g., pulling in a slider or pressing a button) to retract the cartridge 200 a distance relative to the delivery device 400. This relative movement of the shaft 210 of the cartridge 200 with respect to the compacting tool 420 deploys the stent 105 anatomically out of the lumen 238.

[0108] FIG. 5E shows the cartridge 200 disposed within the receptacle 412 of the delivery device 400 such that there is a space between the distal end of the receptacle 412 and the proximal end of the cartridge 200. The depth of this space defines the maximum distance that the cartridge 200 can retract. The stent 105 is positioned near the distal opening 230 from the lumen 238, and the compacting tool 420 advances to its distal position such that the distal end of the compacting tool 420 abuts the proximal end of the stent 105. The distal end 424 of the hook 422 is held within the detent 272, and the second actuator 415 has not yet been actuated. The proximal end 426 of the hook 422 is coupled to the spring 430. When the second actuator 415 is in its pre - actuated rest state, the hook 422 is biased distally to a first configuration. The spring 430 is compressed between the proximal end 426 of the hook 422 and the distal end of the spring 430 housing when the hook 422 is biased distally to the first configuration. When the second actuator 415 is actuated (e.g., pushed downward), the spring 430 is released and biases the proximal end 426 of the hook 422 toward the proximal end of the handle 405. The hook 422 moves proximally and drags the cartridge 200 together, and is coupled to the hook 422 by engagement of the distal end 424 of the hook 422 within the detent 272. The distance that the hook 422 moves proximally retracts the cartridge 200 deeper into the receptacle 412. The compacting tool 420 can remain stationary during the retraction of the cartridge 200. The relative movement between the shaft 210 and the compacting tool 420 deploys the stent 105 from the lumen 238 (see FIG. 5F).

[0109] It should be understood that the additional distal movement of the compacting tool 420 can be used to assist in the deployment of the stent 105 from the lumen 238. Also, the advancement of the compacting tool 420 and the retraction of the cartridge 200 can be controlled by the two actuators 415 as described above, or by a single actuator 415 capable of moving both the pusher and the cartridge 200 depending on the degree of actuation. Further, the shaft 210 can be used to inject an adhesive substance such as viscoelastic using the compacting tool 420 as a plunger during the procedure. The method of implanting and delivering the stent 105 will be described in more detail below.

[0110] Figures 11A - 11C show the steps in the deployment of a stent using a first actuator 415a of a delivery device 400, which in this case can be a slider, to move a pusher from a first loaded position (fully retracted) to a second primed position (at least partially advanced). The first loaded position allows the pusher to be retracted from the distal end region of the delivery device 400, enabling the nose cone assembly 274 (or the entire cartridge 200) to be coupled to the delivery device 400. The second primed position advances the pusher towards the distal end of the delivery device 400 and advances the stent 105 cut through the lumen 238 of the shaft 210. Preferably, the pusher advances to the second primed position before inserting the shaft 210 through the cornea. The delivery device 400 can further incorporate a movable guard 432 configured to prevent the user from inadvertently pushing the slider beyond the second primed position. The guard 432 can be pushed down towards the housing of the delivery device so as to be covered by a guard 432 that prevents the second actuator 415b from being inadvertently actuated. The guard 432 extends beyond at least a portion of the slider track and thereby has a length such that, in addition to blocking the second actuator 415b (FIG. 11B), it blocks further distal movement of the first actuator 415a. When the stent 105 has advanced to the primed position and is ready to be deployed into the eye, the guard 432 can be rotated out of the way revealing the second actuator 415b. The first actuator 415a is free to slide further distally along the track and the second actuator 415b can be pushed down (FIG. 11C). The guard 432 can also be completely removed from the device 400 or the device 400 can be without any guard 432.The housing of device 400 can include one or more marks 434 intended to provide the user with feedback regarding the position of the compacting tool 420 through the shaft 210. The advancement of the compacting tool 420 to one or more positions relative to the housing can also provide the user with tactile feedback, as described elsewhere in this application.

[0111] Figures 12A - 12D show cross - sections of the delivery device 400 before advancing the push rod 420 to the second position and after advancing the push rod 420 to the second position. When the nose cone assembly 274 is attached to the delivery device 400, the first actuator 415 and the compacting tool 420 can advance from their initial retracted first position to the second position. The first actuator 415a and the compacting tool 420 advance to the second position such that the compacting tool 420 can be inserted into the lumen 238 behind the material to be delivered (e.g., the cut stent 105). The guard 432 can prevent the first actuator 415a from sliding beyond the second position. The position of the second position is configured to place the distal tip surface of the compacting tool 420 a predetermined distance (e.g., 6 mm) away from the distal tip of the shaft 210. When the user has created the desired tear and is ready to deliver the material from the lumen, the compacting tool 420 can advance to its third most forward position (assuming the guard 432 does not interfere or is removed from or absent from the device 400). The second actuator 415b can engage to release the material from the shaft 210. As described elsewhere in this application, the second actuator 415b can retract the shaft 210 while the compacting tool 420 remains fixed, ultimately releasing the stent 105 from the lumen. The nose cone assembly 274 retracts and the compacting tool 420 remains fixed.

[0112] The delivery device 400 and the cartridge 200 (or the nose cone assembly 274) can be made into a single use device or may be sterilized and reused. FIGS. 13A-13B illustrate a reset mechanism 436 such that the deployment structure can be reset and the delivery device 400 can be reused. Actuating the reset mechanism 436, for example, sliding a button forward, can return the deployment structure to an armed position. The reset mechanism 436 can also be carried out by pulling the nose cone assembly 274 or the bayonet connector 413 of the delivery device 400 distally until the second actuator 415 returns to its original armed position. The nose cone assembly 274 can be removed from the delivery device 400 and, if desired, loaded with additional material onto the shaft 210 as described elsewhere in this application. The delivery device 400 is provided in an actuated or unactuated state and the user may arm the device during use.

[0113] A nose cone assembly that is transferable between a delivery device and a cutting device can be attached to the main assembly of the cutting device. A tissue patch can be cut by the cutting device and loaded into the nose cone assembly, and then transferred back from the main assembly of the cutting device and coupled to a delivery device for use in deployment to a patient. The configuration of the nose cone assembly can be varied to include any of the transferable cartridges described in this application. In an example, the nose cone assembly can be attached to the cutting assembly by coupling the proximal end of the nose cone to a base such that the longitudinal axis of the lumen of a shaft extending distally from the nose cone aligns with the longitudinal axis of a corresponding conduit exiting a slot. The tissue patch can be positioned within a loading zone area of the base relative to a movable stopper plate of the main assembly. The loading zone and the movable stopper plate can both be part of the base of the main assembly. The patch is placed inside one or more alignment features of the loading zone and can slide forward into a cutting zone until the patch abuts the stopper plate. Once positioned relative to the stopper plate, the tissue patch is sized to a predetermined width by a cutter. The stopper plate provides a calibrated stopping point for the tissue patch prior to cutting. An element configured to hold the tissue patch in this position can be actuated to lower down over the tissue patch and hold the tissue in place, and if necessary compress the tissue to a specific height prior to cutting. When this holding plate is lowered onto the patch and held in place, the cutting lever can be depressed to cut the tissue patch with one or more blades. The stopper plate and the holding plate can move away from the cut stent, and the remainder of the tissue patch is removed from the assembly. The cut stent can be loaded using a tissue loader-slider. The tissue loader-slider can bias the cut stent into position relative to the longitudinal axis of the shaft within the nose cone assembly.For example, an organizational loader-slider can be placed at a predetermined position and slid forward as far as possible until the slider abuts against the ledge of the main assembly, indicating that the cut stent has been completely delivered to the compression channel and is ready to proceed to the shaft of the nose cone assembly. An elongated tool such as a tissue advancement rod can be inserted into the main assembly along the longitudinal axis to bias the cut stent from the main assembly to the shaft of the nose cone assembly. The rod can be configured to advance the tissue slide toward the tip of the nose cone assembly without completely extruding the cut stent from the lumen of the shaft. The nose cone assembly can be removed from the main assembly and attached to the delivery device for deployment to the patient.

[0114] In other examples, the cartridge 200 itself holds a patch of tissue for cutting. For example, FIG. 3A shows that the cover 214 of the cartridge 200 that exposes the recess 221 can be removed from the slot in the base 224. A patch 101 of material can be manually loaded into the recess 221. The patch 101 of material may be dimensioned to receive within the recess 221 or may be trimmed to ensure that it is dimensioned to receive within the recess 221. The cover 214 of the cartridge 200 is replaced onto the base 224 and proceeds through the slot 215 until the lower portion 222 of the cover 214 engages the patch 101 of material and traps it against the protrusion 271. The cover 214, when in the closed configuration, can compress and / or pull on the patch 101 of material within the cartridge 200. FIG. 2 shows that the loaded tissue cartridge 200 can be placed in the receptacle 306 of the cutting device 300 in the open configuration of the handle 343. Once placed, the cutting member 312 is actuated by lowering the handle 343 towards the base 302, whereby the blade 344 of the cutting member 312 can be biased towards the patch 101 of material until the blade 344 completely cuts the patch 101 of material (FIG. 4B). With the blade 344 still in the fully cut position relative to the cartridge 200, the pusher 320 of the cutting device 300 primes the shaft 210 and is biased distally to place the now cut stent 105 towards the opening 230 from the lumen 238 near the distal end region 212 of the shaft 210. The pusher 320 retracts from the cartridge 200 and the cartridge 200 can be removed from the cutting device 300. Removing the cartridge 200 from the cutting device 300, as described elsewhere in this application, can include removing the entire cartridge 200 from the device 300 or detaching the nose cone assembly 274 of the cartridge 200 as shown in FIG. 6.

[0115] The primed tissue cartridge 200 having the severed stent 105 positioned within the lumen 238 of the shaft 210 can be installed with the delivery device 400 (e.g., inserted within the receptacle 412 or attached by a bayonet connector 413 or other attachment mechanism 425). The compacting tool 420 of the delivery device 400 is retracted to its most proximal position and the cartridge 200 is coupled to the delivery device 400. The compacting tool 420 can be advanced using the first actuator 415 from a first retracted position suitable for loading the cartridge 200 to a second primed position such that the delivery device 400 and the cartridge 200 are ready for use on a patient.

[0116] Generally, the stent 105 positioned within the shaft 210 can be transplanted through a clear cornea or a sclerotomy formed using a device separate from the shaft 210 or the cartridge 200. An observation lens such as a gonioscopy lens can be positioned adjacent to the cornea. The observation lens enables viewing of internal regions of the eye such as the scleral spur and the scleral junction from a position in front of the eye. The observation lens may optionally include one or more guide channels sized to receive the shaft 210. Visualization using an endoscope during delivery is also possible. An ultrasound guide can also be used, for example, using a high-resolution biomicroscope or OCT. It is also possible to insert a small endoscope through another limbal incision of the eye to photograph the eye during transplantation.

[0117] The most distal tip 216 of the shaft 210 can penetrate the cornea (or sclera) to access the anterior chamber of the eye. In this regard, a single incision can be made in the eye, such as within the limbus. In one embodiment, the incision is very close to the limbus, such as at the level of the limbus or within 2 mm of the limbus of the clear cornea. The incision can be made using the shaft 210 or a separate cutting device. For example, a device with a blade tip or a diamond knife can be used first to enter the cornea. Then, a second device having a spatula tip can be advanced over the tip of the knife, and the plane of the spatula is arranged to coincide with the dissection plane. The spatula tip device can be the shaft 210.

[0118] The corneal incision can have dimensions sufficient to allow passage of the shaft 210. In one embodiment, the incision is about 1 mm in dimension. In another embodiment, the incision is about 2.85 mm or less in dimension. In another embodiment, the incision is about 2.85 mm or less and greater than about 1.5 mm. Incisions up to 2.85 mm have been observed to be self-sealing incisions.

[0119] After insertion through the incision, the shaft 210 can advance into the anterior chamber along a path that can deliver the stent 105 from the anterior chamber to a target location such as the suprachoroidal space or the suprachoroidal space. With the shaft positioned for the approach, the most distal tip 216 of the shaft 210 can penetrate tissue at the angle of the eye, for example, in the region of the iris root or the ciliary body, or the iris root portion of the ciliary body near the tissue boundary with the scleral spur, as the shaft 210 further advances into the eye.

[0120] The scleral spur is an anatomical landmark located on the wall of the eye's corner. The scleral spur is above the level of the iris and below the level of the spongy retina. In some eyes, the scleral spur can be hidden by the inferior band of the pigmented fibrovascular zone and be located directly behind it. The shaft 210 can move along the path towards the eye's corner and the scleral spur such that the shaft 210 passes near the scleral spur on its way towards the suprachoroidal space, but does not necessarily penetrate the scleral spur during delivery. Rather, the shaft 210 can abut against the scleral spur and move downward to incise the tissue boundary between the sclera and the ciliary body, and the incision entry point begins just below the scleral spur near the iris root or the iris root portion of the ciliary body. In another embodiment, the delivery path of the implant crosses the scleral spur.

[0121] The shaft 210 can approach the eye's corner from the anterior chamber on the same side as the deployment position such that the shaft 210 does not need to travel across the iris. Alternatively, the shaft 210 can approach the eye's corner after crossing the anterior chamber AC such that the shaft 210 travels across the iris and / or the anterior chamber towards the opposite corner of the eye. The shaft 210 can approach the eye's corner via various paths. The shaft 210 does not necessarily need to cross over the eye and does not cross the central axis of the eye. That is, the corneal incision and the location where the stent 105 is implanted into the eye's corner can be in the same quadrant when looking at the eye along the optical axis. Also, the path of the stent 105 from the corneal incision to the eye's corner preferably does not pass through the center line of the eye to avoid interference with the pupil.

[0122] The shaft 210 can continuously advance into the eye, for example, about 6 mm. After the incision plane of the shaft 210 penetrates the iris root or the iris root portion of the ciliary body CB, for example, the stent 105 attached to the shaft can bluntly dissect the boundary between the scleral spur and the tissue layer of the ciliary body CB such that the distal region of the stent 105 extends through the suprachoroidal space and then further lies between the sclera and the tissue boundary of the choroid that forms the suprachoroidal space, following the curve of the inner scleral wall.

[0123] When properly positioned, the stent 105 can be released from the shaft 210. In some examples, the stent 105 can be released by retracting the shaft 210 while a compacting tool 420 prevents the stent 105 from retracting with the shaft 210.

[0124] Once implanted, the stent 105 forms a fluid communication pathway between the anterior chamber and a target pathway (e.g., the suprachoroidal space or the supraciliary space). As noted above, the stent 105 is not limited to being implanted in the suprachoroidal space or the supraciliary space. The stent 105 can be implanted at other locations that provide fluid communication between the anterior chamber and locations within the eye, such as the Schlemm's canal or a subconjunctival location of the eye. In another example, the stent 105 is implanted to form a fluid communication pathway between the anterior chamber and the Schlemm's canal and / or a communication pathway between the anterior chamber and a subconjunctival location of the eye. It should be understood that the devices described in this application can also be used to deliver the stent transsclerally, similar to an approach from inside the eye.

[0125] As described above, the material used to form the stent can be impregnated with one or more therapeutic agents for additional treatment of the eye disease process.

[0126] Various systemic and eye conditions, such as inflammation, infections, cancer growth, etc., may be prevented or treated using the stents described in this application. Specifically, eye diseases such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, and herpes simplex and adenovirus infections can be treated or prevented.

[0127] The following classes of agents can be delivered using the devices of the present invention. Namely, cell transport / motility perturbing agents such as anti-proliferative agents, anti-fibrotic agents, anesthetics, analgesics, colchicine, vincristine, cytochalasin B and related compounds, anti-glaucoma agents including beta blockers such as timolol, betaxolol, atenolol and prostaglandin analogs such as bimatoprost, travoprost, latanoprost, carbonic anhydrase inhibitors such as acetazolamide, methazolamide, dichlorphenamide, Diamox, neuroprotective agents such as nimodipine and related compounds. Additional examples are antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamicin, erythromycin, antibacterial agents such as sulfonamides, sulfacetamide, sulfamethizole, sulfisoxazole, antifungal agents such as fluconazole, nitrofurazone, amphotericin B, ketoconazole, and related compounds, antiviral agents such as trifluorothymidine, acyclovir, ganciclovir, DDI, AZT, foscarnet, vidarabine, trifluorouridine, idoxuridine, ribavirin, protease inhibitors, anti-cytomegalovirus agents, anti-allergy agents such as metapyramine, chlorpheniramine, pyrilamine and profenpyridamine, anti-inflammatory agents such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, fluorometholone, betamethasone, triamcinolone, decongestants such as phenylephrine, naphazoline, tetrahydrozoline, miotics and anti-cholinesterases such as pilocarpine, carbachol, diisopropyl fluorophosphate, phospholine iodide, demecarium bromide, mydriatics such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine, sympathomimetic agents such as epinephrine, vasoconstrictors, vasodilators, and including ranibizumab, bevacizumab and triamcinolone.

[0128] Cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, such as ASPIRIN® from Bayer AG, Leverkusen, Germany; ibuprofen, such as ADVIL® from Wyeth, Collegeville, Pa; indomethacin; mefenamic acid), COX-2 inhibitors including the prodrug Nepafenac® (CELEBREX®, Pharmacia Corp., Peapack, N.J.), immunosuppressants such as sirolimus (RAPAMUNE®, Wyeth, Collegeville, PA), or non-steroidal anti-inflammatory drugs (NSAIDs) such as matrix metalloproteinase (MMP) inhibitors (e.g., tetracycline and tetracycline derivatives) that act early in the pathway of the inflammatory response can also be delivered. Anticoagulants such as heparin, antifibrinogen, fibrinolysin, anticoagulant activase can also be delivered.

[0129] Antidiabetic drugs that can be delivered using this device include acetohexamide, chlorpropamide, glibide, glibenclamide, tolazamide, tolbutamide, insulin, aldose reductase inhibitors, and the like. Some examples of anticancer drugs include 5-fluorouracil, adriamycin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, estramustine, etoposide, etretinate, filgrastim, floxuridine, fludarabine, fluorouracil, fluoxymesterone, flutamide, goserelin, hydroxyurea, ifosfamide, leuprolide, levamisole, lomustine, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, pentostatin, pipobroman, plicamycin, procarbazine, sargramostim, streptozocin, tamoxifen, taxol, teniposide, thioguanine, uracil mustard, vinblastine, vincristine, vindesine.

[0130] Hormones, peptides, nucleic acids, saccharides, lipids, glycolipids, glycoproteins, and other macromolecules can be delivered using this device. For example, endocrine hormones such as pituitary, insulin, insulin-related growth factors, thyroid, growth hormone, heat shock proteins, muramyl dipeptide, cyclosporine, interferon (including α, β, γ interferons), interleukin-2, cytokines, FK506 (epoxypyrido-oxazacyclotricosinetetrone, also known as tacrolimus), tumor necrosis factor, pentostatin, thymopentin, transforming growth factor β2, erythropoietin, etc., immunomodulatory agents, and anticoagulants including anti-angiogenic proteins (e.g., anti-VEGF, interferon) and anticoagulant activating enzymes. Further examples of deliverable polymers include monoclonal antibodies, brain-derived neurotrophic factor (BNGF), ciliary neurotrophic factor (CNGF), vascular endothelial growth factor (VEGF), and monoclonal antibodies directed against these growth factors. Additional examples of immunomodulatory agents include tumor necrosis factor inhibitors such as thalidomide.

[0131] In various examples, the description is made with reference to the drawings, but a particular example may be implemented without one or more of these specific details or in combination with other known methods and configurations. In the description, numerous specific details such as specific configurations, dimensions, and processes are shown to fully understand the examples. In other examples, well-known processes and manufacturing techniques are not described in special detail so as not to unnecessarily obscure the description. Throughout this detailed description, references to "one embodiment", "an embodiment", "one example", "an example", etc. mean that the particular feature, structure, configuration, or property described is included in at least one embodiment or example. Thus, the appearances of the expressions "one embodiment", "an embodiment", "one example", "an example", etc. throughout this specification do not necessarily refer to the same embodiment or example. Further, the particular features, structures, configurations, or properties may be combined in any suitable manner in one or more examples.

[0132] The use of relative terms throughout the detailed description may indicate relative positions and directions. For example, "distal" may indicate a first direction away from a reference point. Similarly, "proximal" may indicate a position in a second direction opposite the first direction. The reference point used in the present application may be the operator, such that the terms "proximal" and "distal" refer to the operator using the device. The region of the device close to the operator may be described as "proximal" in the present application, and the region of the device far from the operator may be described as "distal" in the present application. Similarly, the terms "proximal" and "distal" may be used in the present application to refer to the anatomical position of the patient from the perspective of the operator or along the insertion path from the entry point of the system. Thus, a position that is proximal means a position in the patient that is close to the entry of the device along the insertion path towards the target, and a position that is distal may mean a position in the patient that is away from the entry of the device along the insertion path towards the target position. However, such terms are provided to establish relative frames of reference and are not intended to limit the use or orientation of the device to a particular configuration described in various examples.

[0133] As used herein, the term "about" means a range of values that includes a given value that a person of ordinary skill in the art would consider to be reasonably similar to the given value. In one aspect, about means within one standard deviation using measurements generally accepted in the art. In one aspect, about means a range of plus or minus about 10% of the given value. In one aspect, about includes the given value.

[0134] This specification contains many specific details, but these should not be construed as limitations of the claims or of what may become the claims, but rather as descriptions of features specific to particular embodiments. Specific features described in the context of separate embodiments in this specification 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 sub-combination, in a plurality of embodiments. Further, features may be described and even initially claimed as acting in a particular combination, but one or more features from the claimed combination may in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or a variation of a sub-combination. Similarly, operations are depicted in the drawings in a particular order, but this should not be understood as requiring that the operations be performed in that particular order, or sequentially, or that all of the illustrated operations be performed, to obtain a desirable result. Only some examples and instances are disclosed. Variations, modifications, and extensions of the disclosed examples and instances, as well as other examples, may be made based on what has been disclosed.

[0135] In the foregoing description and claims, the phrase "at least one" or "one or more" may appear following a conjunctive list of elements or features. The term "and / or" may also appear in a list of two or more elements or features. Such phrases are intended to mean any of the recited elements or features individually or any combination of any of the recited elements or features with any of the other recited elements or features, as long as this is not implicitly or explicitly inconsistent with the context in which it is used. For example, the phrases "at least one of A and B," "one or more of A and B," and "A and / or B" are each intended to mean "only A, only B, or both A and B." A similar interpretation is intended for lists containing three or more items. For example, the phrases "at least one of A, B, and C," "one or more of A, B, and C," and "A, B, and / or C" are each intended to mean "only A, only B, only C, both A and B, both A and C, both B and C, or all of A, B, and C."

[0136] The use of the term "based on" in the foregoing and in the claims is intended to mean "at least in part based on," and features or elements not recited are also permissible.

[0137] The systems disclosed in this application may be packaged together in a single package. The completed package is sterilized using a sterilization method such as ethylene oxide or radiation, labeled, and boxed. Instructions for use may be included with the box or provided via an Internet link printed on the label.

Claims

1. A system for preparing a graft and inserting it into a patient's eye, the system comprising: a tissue cartridge, a nose cone including a proximal end region and a distal end region, a distal shaft extending from the distal end region of the nose cone, the distal shaft defining a lumen from a proximal end region to a distal end region of the distal shaft, and at least the distal end region of the distal shaft having a size and shape for insertion into the anterior chamber of the eye; and a tissue cartridge comprising the distal shaft; a delivery device comprising a proximal handle having a distal end region sized and configured to engage and reversibly couple with the proximal end region of the nose cone.

2. The system according to claim 1, wherein the reversible coupling between the proximal end region and the distal end region comprises a male-female connection.

3. The system according to claim 1, further comprising a cutting device, the cutting device comprising a cutting member configured to cut a patch of biologic-derived material onto the graft.

4. The system according to claim 3, wherein the cutting member comprises at least a first blade.

5. The system according to claim 4, wherein the cutting member comprises a second blade spaced from the first blade.

6. Upon actuation of the cutting member, the first blade and the second blade are biased toward and cut at the thickness of the patch of material forming the graft such that the distance is equal to the width of the graft. The system according to claim 5.

7. The system according to claim 3, wherein the cutting device further comprises a handle movably coupled to a base configured to actuate the cutting member.

8. The system according to claim 3, wherein the biologic-derived material is harvested or engineered tissue, an organ, or a portion of an organ.

9. The system according to claim 3, wherein the biologic-derived material is an autograft, allograft, or xenograft material.

10. The system according to claim 3, wherein the biologic-derived material is substantially absorbed after placement of the graft in the eye, and once absorbed, a space remains at the location where the graft was placed.

11. The system according to claim 1, wherein the delivery device further comprises at least one actuator configured to deploy a graft disposed within the lumen of the distal shaft into the eye through the distal opening.

12. The system according to claim 11, wherein the at least one actuator is configured to advance the tool from a first position where the tool is retracted to a second position where the tool is inserted into the lumen behind the graft disposed within the lumen.

13. The system according to claim 12, wherein the at least one actuator is configured to pull the nose cone relative to the tool to deploy the graft from the distal opening.

14. The system according to claim 12, wherein the at least one actuator is configured to advance the tool relative to the nose cone to deploy the graft from the distal opening.

15. The system according to claim 1, wherein the distal shaft of the tissue cartridge is configured to deliver an adhesive substance.

16. The system according to claim 1, wherein the distal shaft is dimensioned to be inserted through a corneal incision of about 2.85 mm or less.

Images