System for shaping and implanting a bio-ocular stent for increasing aqueous outflow and reducing intraocular pressure

Abstract

Systems and methods for preparing an implant and inserting the implant intraocularly into a patient's eye, including a tissue cartridge configured to receive and hold a piece of material; a cutting device; and a delivery device. Related devices, systems, and methods are provided.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to the co-pending U.S. provisional patent applications filed May 20, 2020, Serial No. 63 / 027,689 and March 19, 2021, Serial No. 63 / 163,623, pursuant to 35 USC §119(e). The disclosures of these applications are incorporated herein by reference in their entirety. Background Technology

[0003] The main objective of glaucoma ophthalmic surgery is to increase fluid outflow from the eye. There are several approaches to this type of surgery, including: 1) external trabeculectomy or shunt, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a transscleral outflow path; 2) internal trabecular or transscleral outflow stents or water drainage using hardware-based implantable devices or ablation, non-implantable cutters (e.g., double-blade and trabeculoablation devices); and 3) internal supraciliary stents using implantable non-biological hardware implants.

[0004] Current endovascular stent devices and methods are based on non-biological hardware materials, such as polyimide, polyethersulfone, titanium, and polystyrene-block-isobutylene-block-styrene. These implantable devices based on non-biological hardware have significant drawbacks because they can lead to severe erosion, fibrosis, and damage to ocular tissues, such as endothelial cell loss.

[0005] In view of the foregoing, there is a need for improved devices and methods related to ophthalmic surgery for the treatment of glaucoma. Summary of the Invention

[0006] In one aspect, a system for preparing an implant and inserting the implant into a patient's eye is described. The system includes a tissue cassette configured to receive and hold pieces of material; a cutting device; and a delivery device.

[0007] The tissue cassette may include a shaft extending distally from the cassette. At least a distal region of the shaft is sized and shaped for insertion into the anterior chamber of the eye. The shaft may include an inner cavity. The tissue cassette may also include a base and a cap. The base may be configured to receive a piece of material, while the cap may be configured to hold the piece of material in place on the base. A cutting device may include a cutting member configured to cut the piece of material positioned within the tissue cassette. Cutting the piece of material with the cutting member may form an implant from the piece of material. The implant may be configured for implantation into a patient's eye. A delivery device may include an actuator configured to deploy the implant positioned within the cassette through the inner cavity of the shaft into the eye.

[0008] In one interconnected embodiment, a method for preparing an implant for implantation in a patient's eye and for inserting said implant into the patient's eye is described. The method includes inserting a sheet of material into a tissue cassette. The tissue cassette includes an axis extending from a distal end of the tissue cassette. At least a distal region of the axis is sized and shaped for insertion into the anterior chamber of the eye. The axis includes an inner cavity. The method further includes coupling the tissue cassette to a cutting device. The cutting device has a cutting member configured to cut the sheet of material within the tissue cassette. The method further includes cutting the sheet with the cutting member to form an implant from the sheet while the tissue cassette is coupled to the cutting device; separating the tissue cassette from the cutting device; connecting the tissue cassette to a delivery device; inserting the distal region of the axis into the anterior chamber of the eye; positioning the distal region near ocular tissue; and actuating the delivery device to deploy the implant from the cassette through at least a portion of the inner cavity, thereby engaging the implant with ocular tissue. The method may also include delivering an adhesive material through the axis.

[0009] In one associated embodiment, a system for preparing an implant and inserting the implant into a patient's eye is described. The system includes a tissue cassette configured to receive and hold pieces of material; and a delivery device.

[0010] The tissue cassette may include a shaft extending from a distal end of the cassette. At least a distal region of the shaft may be sized and shaped for insertion into the anterior chamber of the eye. The shaft may include an inner cavity. The tissue cassette may also include a base and a cap. The base may be configured to receive a piece, while the cap may be configured to hold the piece securely to the base. The system may also include a cutting device. The cutting device may include a cutting member configured to cut pieces of material positioned within the tissue cassette. Cutting the pieces of material with the cutting member may form an implant from the pieces. The implant may be configured for implantation into a patient's eye. A delivery device may include an actuator configured to deploy an implant positioned within at least a portion of the cassette into the eye through the inner cavity of the shaft. The tissue cassette may include a nasal cone assembly having a distal region of the tissue cassette and a shaft. The nasal cone assembly may be reversibly coupled to the tissue cassette and reversibly coupled to the delivery device. The shaft of the tissue cassette may be configured to deliver an adhesive material.

[0011] In one interconnected embodiment, a method for preparing an implant for implantation in a patient's eye and for inserting said implant into the patient's eye is described. The method includes inserting a sheet of material into a tissue cassette. The tissue cassette includes an axis extending from a distal end of the cassette. At least a distal region of the axis is sized and shaped for insertion into the anterior chamber of the eye. The axis includes an inner cavity. The method includes coupling the tissue cassette to a cutting device. The cutting device has a cutting member configured to cut the sheet of material within the tissue cassette. The method includes cutting the sheet with the cutting member to form an implant from the sheet while the tissue cassette is coupled to the cutting device; separating at least a portion of the tissue cassette from the cutting device; coupling said at least a portion of the tissue cassette to a delivery device; inserting the distal region of the axis into the anterior chamber of the eye; positioning said distal region near ocular tissue; and actuating the delivery device to deploy the implant from the cassette through at least a portion of the inner cavity, such that the implant engages with ocular tissue. The method may also include delivering an adhesive material through the axis.

[0012] In one associated embodiment, a system for preparing an implant from a sheet of material and inserting the implant into a patient's eye is described. The system includes: a tissue cassette having a nasal cone and a distal axis, the distal axis defining a lumen between the nasal cone and a distal region of the distal axis; a cutting device configured to be coupled to the nasal cone; and a delivery device configured to be coupled to the nasal cone.

[0013] The size and shape of at least the distal region of the distal axis can be designed for insertion into the anterior chamber of the eye. The cutting device may include a base configured to receive a piece of material. The cutting device may include a cutting member configured to cut the piece of material into an implant. The cutting device may also include a clamping tool configured to push the implant into the lumen of the distal axis. The delivery device may include an actuator configured to deploy the implant, clamped in the lumen of the distal axis, into the eye.

[0014] In one interconnected embodiment, a method is described for preparing an implant for implantation in a patient's eye from a sheet of material and for inserting the implant into the patient's eye. The method includes coupling a tissue cassette to a cutting device, the tissue cassette having an axis extending from a distal end of the tissue cassette, at least a distal region of the axis being sized and shaped for insertion into the anterior chamber of the eye. The axis includes a lumen and the cutting device has a cutting member configured to cut the sheet of material. The method further includes cutting the sheet with the cutting member to form an implant from the sheet; compressing the implant within the lumen of the axis; separating the tissue cassette from the cutting device; coupling the tissue cassette to a delivery device; inserting the distal region of the axis into the anterior chamber of the eye; positioning the distal region near ocular tissue; and actuating the delivery device to deploy the implant from the lumen such that the implant engages with the ocular tissue. The method may also include delivering an adhesive material through the axis.

[0015] In one interconnected embodiment, a system for preparing an implant and inserting the implant into a patient's eye is described, including a tissue cassette and a delivery device. The tissue cassette may include a shaft extending distally from the cassette, at least a distal region of which is sized and shaped for insertion into the anterior chamber of the eye. The shaft may include an inner cavity. The system may also include a cutting device having a cutting member configured to cut pieces of material. Cutting the pieces of material with the cutting member can form an implant from the pieces, configured for implantation into a patient's eye. The delivery device may include an actuator configured to deploy the implant, positioned within the shaft, through the inner cavity of the shaft into the eye. The tissue cassette may also include a nasal cone assembly having a distal region of the tissue cassette and the shaft. The nasal cone assembly may be reversibly coupled to the tissue cassette and reversibly coupled to the delivery device. The shaft of the tissue cassette may be configured to deliver an adhesive material.

[0016] In one associated embodiment, a method for preparing an implant for implantation in a patient's eye and inserting said implant into the patient's eye is described, comprising: cutting pieces of material with a cutting member of a cutting device to form an implant from the pieces; compressing the implant within a lumen of an axis extending from the distal end of a tissue cassette; separating at least a portion of the tissue cassette from the cutting device; coupling said at least a portion of the tissue cassette to a delivery device; inserting the distal region of the axis into the anterior chamber of the eye; positioning the distal region near ocular tissue; and actuating the delivery device to deploy the implant from the tissue cassette through at least a portion of the lumen, such that the implant engages with ocular tissue. The method may further include delivering an adhesive material through the axis.

[0017] In one interconnected embodiment, a method for treating an eye with minimally modified biological tissue is described. The biological tissue may be scleral tissue. Minimally modifying the scleral tissue may include compressing the scleral tissue from a first size to a second, smaller size within a distal axis. The size and shape of the distal axis may be designed for insertion into the anterior chamber through a self-sealing incision in the cornea of ​​the eye. The method may further include deploying the compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle. The compressed scleral tissue deployed from the distal axis may be restored towards the first size. The method may further include treating glaucoma with the compressed scleral tissue.

[0018] In some variations, one or more of the following may optionally be included in any feasible combination of the methods, apparatus, devices, and systems described above. Further details are set forth in the accompanying drawings and the following description. Other features and advantages will become apparent from the specification and drawings. Attached Figure Description

[0019] These and other aspects will now be described in detail with reference to the following figures. Generally, the figures are not absolutely or relatively to scale, but are intended to be illustrative. Furthermore, the relative placement of features and elements may be modified for clarity.

[0020] Figure 1A-1B It is a cross-sectional view of the human eye, showing the anterior chamber and vitreous chamber, with the struts in the eye in the example position;

[0021] Figure 2 It is a perspective view of a system according to one embodiment;

[0022] Figure 3A and 3B An embodiment of a tissue box with the lid removed is shown;

[0023] Figure 3C The tissue box with its lid attached is shown;

[0024] Figure 4A An embodiment of a cutting device with a tissue box installed and the cutter in an open configuration is shown;

[0025] Figure 4B A cutting device with a tissue box installed and the cutter in a cutting configuration is shown;

[0026] Figure 4C yes Figure 4B A partial view of the cutting device, showing the cutter;

[0027] Figure 4D yes Figure 4A A partial cross-sectional view of the cutting device;

[0028] Figure 4E yes Figure 4B A partial cross-sectional view of the cutting device;

[0029] Figure 4F-4G A pusher in a forward and backward configuration relative to the base of the cutting device is shown;

[0030] Figure 4H yes Figure 4G A cross-sectional view of the cutting device;

[0031] Figure 4I-4J yes Figure 4F A partial cross-sectional view of the cutting device;

[0032] Figure 5A One embodiment of a conveying device is shown, which is equipped with a tissue box and has a pusher in a forward configuration.

[0033] Figure 5B It shows Figure 5AA conveying device in which the box is retracted relative to the pusher;

[0034] Figure 5C The tissue box and remote area of ​​the delivery device are shown;

[0035] Figure 5D It shows the installation Figure 5C The tissue box inside the delivery device;

[0036] Figure 5E The actuator of the conveyor unit that advances to the deployment position is shown;

[0037] Figure 5F The tissue box is shown, which is retracted by a delivery device to deploy a cutting scaffold inside the eye;

[0038] Figure 6 It is a perspective view of the system according to the relevant implementation method;

[0039] Figure 7A and 7B A tissue box with a lid in a loading configuration is shown;

[0040] Figure 7C It shows the one with the cover installed. Figures 7A-7B tissue box;

[0041] Figure 8 Embodiments of the cutting device and tissue box are shown;

[0042] Figure 9A An embodiment of a cutting device is shown, which is equipped with a tissue box, the cutter is in a cutting configuration, and the nose cone of the tissue box has been separated.

[0043] Figure 9B One embodiment of the delivery device is shown, which has a nose cone that engages with a tissue box and a pusher in a retracted configuration.

[0044] Figure 9C It shows Figure 9B The conveying device, wherein the actuator advances to the prepared structure;

[0045] Figure 9D It shows Figure 9C The conveying device in which the nose cone retracts relative to the pusher;

[0046] Figure 10A The nose cone is shown before it engages with the distal region of the delivery device;

[0047] Figure 10B The nose cone is shown after engagement with the distal region of the delivery device and before attachment;

[0048] Figure 10C A nose cone is shown engaging and attaching to the distal region of the delivery device;

[0049] Figure 11A The actuator is shown in its first retracted position;

[0050] Figure 11B The actuator for advancing to the second ready position is shown;

[0051] Figure 11C The distal axis located inside the eye and the third actuator ready to be activated are shown;

[0052] Figure 12A-12B It is displayed Figure 11A A cross-sectional view of the device in its first retracted position;

[0053] Figure 12C-12D It is displayed Figure 11B A cross-sectional view of the device in the second ready position;

[0054] Figures 13A-13B The reset mechanism of the transmission device is shown;

[0055] Figures 14A-14H An embodiment of a cutting assembly for cutting a stent and transferring the stent to a portion of a tissue cassette is shown;

[0056] Figure 14I An embodiment of the nose cone assembly connected to the cutting assembly is schematically shown;

[0057] Figures 15A-15B Another embodiment of the cutting device for cutting a support is shown.

[0058] It should be understood that the accompanying drawings are merely illustrative and are not intended to be drawn to scale. It should also be understood that the apparatus described herein may include features that are not necessarily depicted in every figure. Detailed Implementation

[0059] Implants, systems, and methods for increasing water outflow from the anterior chamber of the eye are disclosed. As will be described in detail below, endovascular outflow scaffolds using biological, cell-based, or tissue-based materials provide enhanced biocompatible water outflow with improved tolerability and safety compared to conventional shunts. In one exemplary embodiment, a cutting device—also referred to herein as a trephine device or cutting tool—is used to harvest or generate biological tissue or bio-derived material in vitro and form an implant, also referred to herein as a scaffold. In one embodiment, the scaffold is an elongated body or material having an internal lumen to provide a pathway for drainage. In a preferred embodiment, the scaffold is an elongated body or tissue strip without an internal lumen and configured to retain the tear and provide a supraciliary scaffold. Lumen-based devices may be limited by the lumen acting as a fibrotic occlusion pathway. The scaffold formed from this tissue is then implanted into the eye through an endovascular delivery pathway to provide water outflow from the anterior chamber. The scaffolds described herein can be used as a phacoemulsification-assisted or stand-alone treatment for glaucoma as part of minimally invasive glaucoma surgery (MIGS).

[0060] The use of terms such as stent, implant, shunt, biological tissue, or tissue is not intended to limit any one type of structure or material. An implanted structure may, but does not need to, be a material that is substantially absorbed into the ocular tissue after placement in the eye—so that space can remain in the location where the structure previously stood once absorbed. Once implanted, the structure may also remain in place for an extended period and be substantially free from corrosion or absorption.

[0061] As will be described in more detail below, the scaffolds described herein may be made of bio-derived materials that do not cause toxic or harmful effects when implanted in a patient.

[0062] The term "bio-derived material" includes naturally occurring biomaterials and synthetic biomaterials and combinations thereof suitable for implantation in the eye. Bio-derived materials include materials that are natural biological structures having a biological arrangement naturally present in a mammalian subject, including organs or organ portions formed from tissue, and tissues formed from materials assembled according to structure and function. Bio-derived materials include tissues such as corneal, scleral, or cartilage tissue. Tissues considered herein may include any of a variety of tissues, including muscle, epithelium, connective tissue, and neural tissue. Bio-derived materials include tissues, organs, organ portions, and tissues from a subject harvested from a donor or patient, including a piece of tissue suitable for transplantation, including autologous, allogeneic, and xenograft materials. Bio-derived materials include naturally occurring biomaterials, including any material naturally present in a mammalian body. As used herein, bio-derived materials also include materials engineered to have a biological arrangement similar to a natural biological structure. For example, this material can be synthesized using in vitro techniques, such as by seeding a three-dimensional scaffold or matrix with appropriate cells, engineered, or 3D-printed materials to form a biostructure suitable for implantation. Bio-derived materials, as used herein, also include cell-derived materials, including stem cell-derived materials. In some embodiments, bio-derived materials include injectable hyaluronic acid hydrogels or adhesive materials, such as GEL-ONE crosslinked hyaluronic acid (Zimmer).

[0063] In some embodiments, the bio-scaffold can be an engineered or 3D-printed material formed into a tubular shape having an inner cavity extending from a proximal opening to a distal opening. The tube can also be printed to incorporate multiple openings throughout. For example, the walls of the printed material can be designed to have multiple openings, allowing fluid within the cavity to seep out or flow outward through the tube walls, making the tube sufficiently porous to ensure water drainage from the eye. The tube can be printed to have dimensions that can be modified during or near delivery. For example, the 3D-printed material can be designed to have a first dimension that facilitates manual handling. During or near delivery, the 3D-printed material can be cut to a size more suitable for implantation in the eye. In cases where material sheets are described as being cut or trephinated into a scaffold prior to implantation, it should be understood that the material sheets can be printed material with a specific 3D shape (e.g., including tubular shapes) and cut into a scaffold by cutting to shorter desired lengths. Therefore, in some embodiments, the scaffold described herein need not be solid and may also incorporate an inner cavity.

[0064] The biologically derived material used to form the scaffold, sometimes referred to herein as biological tissue or biomaterial, can vary and can be, for example, corneal tissue, scleral tissue, cartilage tissue, collagen tissue, or other rigid biological tissue. Biological tissue can be hydrophilic or hydrophobic. The biological tissue may include or be impregnated with one or more therapeutic agents for additional treatment of eye diseases.

[0065] Biological scaffold materials can be used in combination with one or more therapeutic agents, thus enabling them to be used for additional drug delivery to the eye. In one embodiment, biological tissue can be embedded in sustained-release pellets or immersed in a therapeutic agent for sustained-release delivery to the target tissue.

[0066] Non-biological materials include synthetic materials prepared through artificial synthesis, processing, or manufacturing. These synthetic materials may be biocompatible, but are not cell- or tissue-based. Examples of non-biological materials include polymers, copolymers, polymer blends, and plastics. Non-biological materials include inorganic polymers such as silicone rubber, polysiloxanes, and polysilanes; and organic polymers such as polyethylene, polypropylene, polyethylene compounds, and polyimides.

[0067] Regardless of the source or type of the biologically derived material, it can be cut or trephinated into an elongated shape suitable for use as a scaffold and implantation in the eye. The cutting process of the tissue can be performed before or during the surgical implantation procedure. The scaffold (one or more) implanted in the eye may have a structure and / or permeability that allows water to drain from the anterior chamber when positioned within the ciliary body dissection suture.

[0068] Biologically derived materials can be tissues that are minimally modified or manipulated for use in the eye. Minimally modified biologically derived materials do not involve combinations of the material with other articles, except for, for example, water, bactericides, preservatives, cryopreservatives, storage agents, and / or drugs or therapeutic agents (one or more). Minimally modified biologically derived materials do not produce systemic effects once implanted, and their primary function does not depend on the metabolic activity of any living cells. During each step of the preparation and use method, the biologically derived material can be manipulated to a minimum, thereby preserving the original, relevant characteristics of the biological tissue. The scaffold can be a structural tissue that provides physical support or serves as a barrier or conduit, for example, by at least partially retaining the ciliary slit formed in the eye. The scaffold cut from the biologically derived material can be minimally manipulated by compression, clamping, folding, rolling, or other types of temporary manipulation of the scaffold, allowing the material to revert to its original structure once released from the applied compressive or clamping force. Therefore, minimal manipulation can temporarily and mechanically alter the size or shape of cut tissue while retaining the tissue's original, relevant characteristics relating to its utility for reconstruction, repair, or replacement once this mechanical alteration is removed. For example, a bio-derived material could be the sclera, cut into a shape too large for the inner diameter of the delivery tube through which it is implanted. Minimal manipulation of the cut scaffold could include temporarily compressing the scleral material into the lumen of the delivery tube, such that after implantation into the eye, the cut scaffold tends to revert to its original cut dimensions. Although the bio-derived materials described herein are described in the context of being cut into scaffold-like implants—which can maintain a rupture for water outflow—other approaches are envisioned. For example, the bio-derived material could be compressed into a plug and then implanted in a region of the eye for other purposes, such as scaffolding, occlusion of traumatic ruptures, over-filtered bubbles, posterior wall ruptures, and other indications.

[0069] Figure 1A-1B This is a cross-sectional view of the human eye, showing the anterior chamber (AC) and vitreous chamber (VC). The stent 105 can be positioned intraocularly at the implantation site such that at least a first portion of the stent 105 is positioned within the anterior chamber (AC), and a second portion of the stent 105 is positioned within tissue, such as within the supraciliary space and / or suprachoroidal space of the eye. The stent 105 is sized and shaped to allow it to be positioned in such a configuration. The stent 105 provides or otherwise serves as a channel for the flow of aqueous humor away from the anterior chamber (AC) (e.g., to the supraciliary space and / or suprachoroidal space). Figure 1A-1BIn the diagram, the support 105 is schematically represented as an elongated body relative to the transmission shaft 210. It should be understood that the size and shape of the support 105 can vary. Furthermore, the size and shape of the support 105 before insertion into the transmission shaft 210 can be changed during insertion into the transmission shaft 210, and can be changed after deployment from the transmission shaft 210.

[0070] Bracket 105 can be internally routed ( ab interno Implantation can be performed, for example, through a clear corneal or scleral incision. A stent can be implanted to create an opening or gap to enhance outflow communication between the anterior chamber AC and the supraciliary space, the anterior chamber AC and the suprachoroidal space, the anterior chamber AC and the Schlemm's canal, or the anterior chamber AC and the subconjunctival space, or any other ocular compartment, tissue, or interface clinically indicated by scleral, subscleral, or suprascleral occlusion, stent placement, and / or tissue reinforcement. In a preferred embodiment, the stent 105 is implanted such that its distal end is positioned within a supraciliary location, and its proximal end is positioned within the anterior chamber AC to provide a supraciliary gap. The distal end of the stent 105 may be positioned between other anatomical parts of the eye.

[0071] Traditional glaucoma stents are typically made of non-biological materials, such as polyimide or other synthetic materials, which can cause endothelial tissue damage, leading to progressive, long-term, and irreversible corneal endothelial loss. The stent materials described herein can reduce and / or eliminate the risk of this tissue damage while still providing enhanced aqueous humor outflow.

[0072] The scaffold 105 described herein can be formed from any of a variety of bio-derived materials having permeability and / or structure that allows water filtration through it. The scaffold 105 can be formed from harvested, engineered, grown, or otherwise manufactured bio-derived materials. The bio-derived scaffold material can be obtained or harvested from a patient or donor. The bio-derived scaffold material can be harvested before or during surgery. The bio-derived scaffold material can be synthetic biological tissue generated using in vitro techniques. The bio-derived material can be stem cell-derived or bioengineered. The tissue can be generated through in situ cellular or non-cellular growth. In one example embodiment, the tissue can be 3D printed during manufacturing. The bio-derived material can be a material with minimal manipulation and retain its original structural features as tissue.

[0073] 3D-printed tissue can be printed as larger sheets of material, which are then cut during surgery, as described elsewhere herein. Alternatively, 3D-printed tissue can be printed to have the final size of an implantable scaffold. In this embodiment, the 3D-printed material does not need to be cut before implantation and can be directly implanted. For example, a 3D-printed scaffold can be printed directly into a cassette configured to be operatively coupled to a delivery device described herein, which in turn is used to deploy the 3D-printed scaffold into the eye. Biofabrication The 3D printing process described in (Biomanufacturing), 2019; 11(3) generates 3D printed scaffolds.

[0074] In one example embodiment, the scaffold 105 is made of biological tissue. The bio-derived material can be corneal tissue and / or non-corneal tissue. The bio-derived material may include corneal, scleral, collagen, or cartilage tissue. In one embodiment, the bio-derived scaffold material may be bare corneal stroma tissue without epithelium and endothelium, which is porous and hydrophilically permeable to allow water filtration. The bio-derived material may be a minimally manipulated sclera that retains its original structural features as tissue. The bio-derived material of the scaffold 105 may, but does not necessarily, integrate into the inherent anatomy of the eye after placement. The scaffold can allow surrounding tissue to form pathways that remain open for extended periods, even after the scaffold is absorbed. The bio-derived scaffold material may not be significantly absorbed or integrated into the anatomy of the eye, allowing the scaffold 105 to remain implanted for extended periods or indefinitely as needed.

[0075] In other embodiments, the scaffold 105 material may be made of complex carbohydrates or non-inflammatory collagen. The scaffold 105 may also be formed of biodegradable or bioabsorbable materials, including biodegradable polymers, including hydroxyaliphatic carboxylic acids, homopolymers or copolymers such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid; polysaccharides such as cellulose or cellulose derivatives such as ethyl cellulose, cross-linked or uncross-linked sodium carboxymethyl cellulose, sodium carboxymethyl cellulose starch, cellulose ethers, cellulose esters (such as cellulose acetate, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, and calcium alginate), polypropylene, polybutyrate, polycarbonate, acrylate polymers such as polymethacrylate, polyanhydride, polyvalerate, polycaprolactone such as poly-c-caprolactone, polydimethylsiloxane, polyamide, polyvinylpyrrolidone, polyvinyl alcohol phthalate, waxes (such as paraffin and beeswax), natural oils, shellac, zein, or mixtures thereof. The scaffold 105 may be formed of hyaluronic acid hydrogels or adhesive materials.

[0076] As described above, bio-derived scaffold materials can possess permeability or porosity that allows water filtration to adequately control or regulate intraocular pressure. Permeable biological tissues (e.g., sclera, cornea, collagen, etc.) are preferred scaffold materials; however, any biological tissue, even if impermeable, is considered here as a potential scaffold material for use as a structural spacer that keeps the ciliary body open. Preferably, the scaffold material can create gaps that allow fluid flow. The created gaps can extend longitudinally along each side of the scaffold. If the scaffold material is permeable, more fluid can pass through the ciliary body compared to a case where the scaffold material is impermeable and fluid needs to pass along the outside of the scaffold. Therefore, the materials considered herein do not need to be porous to provide the desired function; however, this function can be enhanced by the porosity of the material.

[0077] Typically, bio-derived scaffold materials possess a certain degree of rigidity and intraocular durability, allowing them to retain outflow from the anterior chamber; however, they are softer compared to conventional non-bio-derived polyimide shunts used in glaucoma treatment (e.g., CYPASS, Alcon). The scaffold material can have sufficient structure to act as a spacer to support sustained outflow through the ciliary body. Once implanted within the ciliary shunt, the scaffold material can maintain its structural height or thickness, thereby providing fluid flow through or around the scaffold. In some embodiments, the cutting scaffold is minimally manipulated by compression or clamping into a delivery shaft, such that the size and / or shape of the cutting scaffold decreases within the shaft from a first size to a second, smaller size. The size and shape of the delivery shaft can be designed for insertion into the anterior chamber through the cornea (e.g., a self-sealing incision in the cornea) and advancement toward the iridocorneal angle. The delivery shaft can deploy the clamped scaffold between tissue layers near the angle. Once the clamped scaffold is deployed from the delivery shaft, it can begin to recover toward its original shape and / or size. Once implanted, the bio-derived scaffold can be made smaller than or the same as its original shape and / or size. Minimally modified biological tissue can be used to treat glaucoma. Compared to traditional non-biological materials such as polyimide, bio-derived scaffold materials offer advantages in biocompatibility, anatomical consistency, and water permeability. Bio-derived scaffold materials can provide better compliance and conformity to the scleral wall, and are less likely to cause endothelial and scleral erosion / loss over time and with prolonged eye rubbing and blinking.

[0078] Typically, allogeneic transplant tissues used for implantation in the eye are carefully processed to avoid altering their original state. The scaffolds described in this article do not require such fine processing and can be minimally modified by compression or clamping or otherwise wedging into a smaller space to allow for intraocular delivery to the eye via corneal or scleral incisions for intraocular stenting, occlusion, reinforcement, or puncture (less than approximately 3.5 mm).

[0079] In one embodiment, the material for forming the scaffold is provided as uncut sheets of material configured for manual loading into the cassette 200. The uncut sheets of material may also be cut by a cutting component independent of the cassette 200 and then transferred to an area of ​​the cassette 200. As will be discussed in more detail below, cutting can be performed during or before surgery. In some embodiments, the scaffold is formed by 3D printing and can be printed to the desired final size for the scaffold, or can be printed as sheets of material that are then cut during or before surgery. Cutting achieved by the apparatus described herein can provide thin strips of material implantable in the eye to provide regulation of water outflow. The cutting or trephineing process can position the cut implant within the conduit or lumen of the cassette, such that the cut implant held within the cassette can subsequently be transferred from the delivery device without removal or transfer from the cassette. Alternatively, cutting can be performed independently of transferring the cut implant into the delivery device. Cutting and transferring the cut implant into the delivery device can be separate steps performed by separate tools or components. For example, the system may combine a first device for cutting a piece of material into a cut implant, a second device for transferring the cut implant to a delivery device, and a third device for deploying the cut implant from the delivery device into the eye. It should be understood that cutting, transfer, and deployment may be integrated into a single device, or one or more of these may be separate devices used in combination to transform a piece of material into a cut implant for deployment in the eye. In a preferred embodiment, cutting and transfer of the cut implant are integrated into the first device, and deployment of the cut implant in the eye is performed in the second device.

[0080] As used herein, the term "sheet of material" refers to a piece of bio-derived material whose dimensions along at least one dimension are larger than the dimensions of a scaffold cut from the sheet of material and implanted into the object. In some embodiments, the sheet of material may have a generally square shape, and the scaffold cut or trephinated from the sheet of material may have a generally rectangular shape. For example, the sheet of material may be about 7 mm wide x 7 mm long x 0.55 mm thick, while the scaffold cut from the sheet of material may be 0.3-1.0 mm wide x 7 mm long x 0.55 mm thick. The dimensions of the sheet of material and the cut scaffold may vary. The sheet of material before cutting may be between about 5 mm and about 10 mm wide, between about 5 mm and about 10 mm long, and between about 0.25 mm and about 2 mm thick. The scaffold cut from the sheet of material may be between about 0.3 mm and about 2 mm wide, preferably between 0.7 mm and 1.0 mm wide. The scaffold cut from the sheet of material may be between about 5 mm and about 10 mm long. The stent cut from the material sheet can be between 0.25 mm and 2 mm thick. The material sheet and the cut stent can each have the same length and thickness, but different widths. The material sheet and the stent cut from it can also have different lengths and thicknesses. For example, the material sheet can have a first thickness and the stent cut from it can have the same thickness, but can be folded or rolled into a different thickness than the material sheet when implanted. The cut stent does not need to be rectangular and can have non-rectangular shapes, such as a wedge or any of a variety of shapes, to provide specific clinical outcomes. For example, a stent cut into a “dog bone” shape with enlarged distal and proximal ends can provide additional fixation within the target tissue. The stent can be cut into a narrow, elongated shape at the anterior end and enlarged at the posterior end to provide ease of insertion and at least one end for fixation.

[0081] In some embodiments, the sheet of material can have a relatively large width (e.g., 10 mm x 10 mm), and the stent is cut from the sheet into strips with a much smaller width (e.g., about 1.0 mm to about 1.5 mm), and then the cut stent is pressed 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. Even if the stent is not excessively large relative to the conduit and therefore remains unpressurized, the stent can substantially fill the inner diameter of the delivery conduit. The stent can be excessively large relative to the internal dimensions of the conduit and is pressed into the conduit to substantially fill it. Furthermore, the size of the cut stent can vary depending on the size of the conduit through which the stent is to be deployed. For example, the inner diameter of the delivery conduit can be about 600 micrometers to about 800 micrometers. Therefore, depending on whether the stent is to be pressed into the delivery conduit and depending on the internal dimensions of the delivery conduit, the stent can be cut or trephineed into any of a variety of sizes.

[0082] The stent cut from the material sheet can have width, length, and thickness. In one embodiment, the width of the stent cut from the material sheet using the cutting device described herein can be at least 100 micrometers up to about 1500 micrometers, or between 100 micrometers and 1200 micrometers, or between 100 micrometers and 900 micrometers, or between 300 micrometers and 600 micrometers. The stent cut from the material sheet can have a width of at least about 100 micrometers and a width not exceeding 1500 micrometers, 1400 micrometers, 1300 micrometers, 1200 micrometers, 1100 micrometers, 1000 micrometers, 900 micrometers, not exceeding 800 micrometers, not exceeding 700 micrometers, not exceeding 600 micrometers, not exceeding 500 micrometers, not exceeding 400 micrometers, not exceeding 300 micrometers, or not exceeding 200 micrometers. The length of the stent cut from the material sheet can vary depending on the location of stent implantation. In some embodiments, the length of the stent is between 1 mm and 10 mm, or more preferably between 3 mm and 8 mm. The thickness of the scaffold cut from a sheet of material can range from 100 micrometers to about 800 micrometers, or from 150 micrometers to about 600 micrometers. In one embodiment, the biomaterial forming the scaffold can have a thickness of not less than 100 micrometers and not more than 5 mm. The thickness of the scaffold can also depend on whether the scaffold is folded or rolled up during implantation, such that a sheet of material with a thickness of only 250 micrometers can be cut into a scaffold and the scaffold can be folded during implantation to double the thickness to about 500 micrometers. The thickness of the scaffold can also depend on what bio-derived material is used. For example, scleral or corneal tissue can typically have a thickness of about 400 micrometers, but can shrink to about 250-300 micrometers after harvesting. Therefore, a scaffold cut from a shrunken sheet of corneal tissue may only be 250 micrometers thick.

[0083] In some embodiments described in more detail below, the stent is cut from a sheet of material to substantially fill a catheter through which it is advanced for delivery. In other embodiments, the stent can be cut into an implant that is excessively large relative to the size of the catheter through which it is deployed. In this embodiment, the stent can be cut to have a first size that is excessively large compared to the internal dimensions of the delivery catheter. The excessively large stent can be prepared within the delivery conduit, for example, by clamping or compressing it with a tool, such that when prepared within the conduit, the stent presents a second, smaller size. After deployment in the eye and release of the stent from the delivery conduit, the stent can achieve a third size close to its original first size. This will be described in more detail below.

[0084] In one non-limiting example, the biological tissue scaffold has dimensions of not less than 0.1 mm and not more than 8 mm in any direction, and a thickness of not less than 50 micrometers and not more than 8 mm. In one non-limiting example, the scaffold is approximately 6 mm long, approximately 300-600 mm wide, and approximately 150-600 mm thick. Cuts can be not less than 1 mm and not more than 8 mm in any direction. In one non-limiting example, the cut tissue has dimensions of 100-800 micrometers wide and 1 mm-10 mm long. It should be understood that multiple scaffolds can be delivered to one or more target sites during the implantation procedure.

[0085] Figure 2 and 6 Interrelated embodiments of a system 100 for preparing and delivering a biological intraocular scaffold to increase water outflow and reduce intraocular pressure are shown. The system 100 may include a tissue cassette 200 having at least a portion configured to be reversibly and operatively coupled to a cutting device 300 and a delivery device 400.

[0086] Each system 100 can be provided without the cutting device 300 and includes only the tissue cassette 200 and the delivery device 400. In this embodiment, the tissue cassette 200 may include a pre-cut support 105 within the cassette 200, ready to engage with the delivery device 400 for deployment into the eye. The cassette 200 with the pre-cut support 105 can be immersed in a stable solution. Therefore, when the system is described as including the cutting device 300, it should be understood that the cutting device 300 may not be used during surgery, and instead the support 105 is provided in a pre-cut and / or prepared configuration within at least a portion of the delivery device 400 or the tissue cassette 200.

[0087] Figure 2 A first cartridge 200, shown as separate from the cutting device 300, and another cartridge 200 equipped with a delivery device are displayed. The cartridge 200 is configured to receive and hold a piece 101 of material within itself in preparation for cutting by the cutting device 300. The cutting device 300, when operatively engaged with the cartridge 200, is configured to form a bio-endocular scaffold 105 from the piece 101 of material held within the cartridge 200. The delivery device 400, when operatively engaged with the cartridge 200, is configured to deliver the cut implant 105 from the cartridge 200 to the implantation site. Figure 2 In the embodiment, the tissue box 200 is configured to cooperate with both the cutting device 300 and the conveying device 400, such that the entire tissue box 200 is removed from the two devices 300 and 400 of the system 100 and transferred between the two devices 300 and 400.

[0088] Figure 6An interconnected embodiment of system 100 is shown, including a tissue cassette 200 configured to be operatively coupled to a cutting device 300 and a conveying device 400. However, the entire tissue cassette 200 does not need to be completely removed from the cutting device 300 for coupling with the conveying device 400. In this embodiment, the tissue cassette 200 may include a distal nasal cone assembly 274 configured to separate from the proximal portion 207 of the cassette 200 and to be coupled to the conveying device 400. The nasal cone assembly 274 may include at least a portion of the distal portion 205, such as a nasal cone 275 and a shaft 210 extending distally from the nasal cone 275.

[0089] In other embodiments, the cassette 200 may not need to include a portion configured to receive the sheet 101 of material within the cassette 200. For example, the cassette 200 may only include a nasal cone assembly 274, which includes a nasal cone 275 having a distal axis 210. The nasal cone 275 having the distal axis 210 may be coupled to a cutting device 300, which is configured to receive the sheet 101 of material in at least one region and hold the sheet 101 of material in preparation for cutting by the cutting device 300. The nasal cone 275 and the distal axis 210 may be arranged relative to the cutting device 300 such that a cutting support can be transferred therein for deployment in the eye. Figure 14I A nasal cone assembly 274 coupled to a cutting assembly 500 is schematically shown. The nasal cone assembly 274 includes a nasal cone 275 having a proximal end coupled to the cutting assembly 500 and a distal shaft 210 extending from the nasal cone 275 along a longitudinal axis A. The cutting assembly 500 may be part of a cutting device 300 as described herein.

[0090] The cassette may include any of the various structural arrangements described herein, but generally refers to a component that can be transferred between two or more devices. The cassette can be transferred between a cutting device and a conveying device. The cassette may be configured to hold pieces of material for cutting into a scaffold and to provide a conduit for deploying the scaffold into the eye. However, the cassette need not be configured to hold pieces of material for cutting. The cassette may include a shaft configured to receive the cut scaffold from the cutting assembly and then deploy the scaffold from the shaft into the eye. Any of the various configurations described herein is envisioned.

[0091] Each of these systems and their respective components will be described in more detail in this article.

[0092] Figure 2 besides Figures 3A-3COne embodiment of a tissue cassette 200 is shown, configured to hold pieces of material for cutting and to provide a conduit for deploying a cutting stent into the eye. The cassette 200 may include a distal portion 205 coupled to and extending distally from a proximal portion 207. The distal portion 205 may include an elongated member or shaft 210 having an internal conduit or lumen 238 sized to receive and deploy a stent 105. The proximal portion 207 may include a base 224 and a cap 214 movably attached to the base 224. The proximal portion 207 is intended to be held externally to the eye, while the distal portion 205 is configured to be inserted into the eye to deploy the stent 105 within target tissue. The implant 105 can be advanced from the proximal portion 207 of the cassette 200 into a deployment positioned within the distal portion 205 of the cassette 200. The distal portion 205 of the cartridge 200 can be inserted into the anterior chamber of the eye, thereby positioning it near the ocular 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 via an intracorneal incision, while the proximal portion 207 of the cartridge 200 remains outside the eye (e.g., connected to the delivery device 400).

[0093] Figure 6 besides Figures 7A-7C Another embodiment of the tissue cassette 200 is shown, configured to hold pieces of material for cutting and to provide a conduit for deploying a cutting stent into the eye. The tissue cassette 200 may include a distal portion 205 coupled to and extending distally from a proximal portion 207, the proximal portion 207 including a shaft 210 having dimensions for receiving and deploying an internal conduit or lumen 238 (in) of the stent 105. Figure 14I (See below). The proximal portion 207 may also include a base 224 and a cover 214 movably attached to the base 224. The distal portion 205 and the shaft 210 may be removably attached to the proximal portion 207 of the housing 200. For example, the proximal portion 207 may be retained within the cutting device 300, while a removable nose cone assembly 274 including the nose cone 275 and the shaft 210 may detach from the proximal portion 207 and engage with the delivery device 400 (see below). Figures 9A-9D ).

[0094] It should be understood that the distal portion 205 of the cartridge 200 can be used for other delivery pathways (e.g., transscleral delivery). Deploying the implant 105 into ocular tissue may include the implant 105 being at least partially located between the ciliary body and the sclera of the eye. The implant 105 may be located between the ciliary body and the sclera, within a ciliary body separation opening.

[0095] The shaft 210 of the cartridge 200 (also referred to herein as an inlet tube, applicator, conduit, or delivery body) extending distally outward from the proximal portion 207 of the cartridge 200 includes at least a portion extending along the longitudinal axis A. At least another portion of the shaft 210 may be angled, curved, or flexible, such that it may form a distal curve or bend away from the longitudinal axis A. In some embodiments, the shaft 210 may include flexible and rigid portions, such that the shape of the shaft changes depending on the relative positions of these portions. Figures 3A-3C besides Figures 7A-7CThe illustrated embodiment has a proximal portion extending along a longitudinal axis A and a distal region 212 curving downward away from the longitudinal axis A. This distal region 212 may include an opening 230 from an inner cavity 238 through which the support 105 can be deployed. The opening 230 from the inner cavity 238 may be positioned in a plane perpendicular to the plane of the longitudinal axis A of the distal region 212 of the shaft 210. The opening 230 from the inner cavity 238 may also be positioned in a plane angled relative to the longitudinal axis A of the distal region 212 of the shaft 210. The distal region 212 of the shaft 210 may be tilted such that the opening 230 into the inner cavity 238 is elongated rather than circular, and the distal end 216 of the shaft 210 extends beyond the opening 230. The distal end 216 of the shaft 210 may be a pointed end or a blunt end (which is square so that it does not form a sharp point). The shape of the opening 230 can be a function of the overall cross-section of the shaft 210 at the distal region 212 and the angle of the opening 230 relative to the longitudinal axis A of the distal region 212. For example, if the distal region 212 of the shaft 210 has a rectangular cross-section and the opening 230 is cut perpendicularly to the longitudinal axis A, then the cross-sectional shapes of the opening 230 and the shaft 210 are substantially matched. If the shaft 210 has a rectangular cross-section and the opening 230 is cut less perpendicularly to the longitudinal axis A, then the opening 230 can have an elongated rectangular shape compared to the rectangular shape of the shaft 210. The opening 230 can also have a first shape near the base of the ramp and a second shape near the distal end 216. For example, the opening 230 near the base of the ramp can be circular and the opening 230 near the distal end 216 can be square. It should also be understood that the opening 230 does not necessarily have to be located at the distal end of the shaft 210. An opening 230 may be formed in the sidewall of the shaft 210 such that the support 210 is pushed out of the cavity 238 along a direction angled relative to the longitudinal axis of the cavity 230. The opening 230 may be positioned relative to the housing 200 within the shaft 210 such that it is positioned at the front, lower, upper, and / or other side of the shaft 210. The distal region 212 of the shaft 210 may have a circular, elliptical, rounded rectangular, rectangular, rounded square, square, rhomboid, teardrop, or other cross-sectional shape, and the distal end 216 may have a varying distal shape, including a blunt end, a bullet end, a scraper end, or a pointed end. The distal region of the shaft 210 may have any of the many constructions known in the field of ophthalmology.

[0096] Axis 210 can be used to create a ciliary body separation slit within the supraciliary space of the ciliary body. The distal region of axis 210 can be shaped to form the slit and provide a conduit for delivering material into the supraciliary space of the eye. Axis 210 can also be used to deliver viscous materials, such as viscoelastic fluids, or non-viscous materials, such as scleral tissue. For example, viscoelastic materials can be delivered to an area of ​​the eye via axis 210 before, during, and / or after stent implantation. A corneal incision can be made with a surgical scalpel or other tools, and axis 210 is inserted through the incision, with the distal end of axis 210 navigated to the desired location for delivery. The distal end of axis 210 may include a scraper for separating tissue layers and creating a ciliary body separation slit within the supraciliary space between the sclera and ciliary body. The size, surface finish, and shape of the distal end can be designed to minimize trauma. Axis 210 may additionally include one or more markers providing user information about the insertion distance. The distal region of axis 210 may include one or more markers for angular reference of how deep the tongue of axis 210 has been inserted into the supraciliary space of the ciliary body. The length of axis 210 is sufficient to allow use of the device from a temporal or superior position.

[0097] The shaft 210 of the housing 200 is sized and shaped for internal access via a clear corneal incision, allowing the stent 105 to exit from its distal end. In at least some embodiments, the distal region 212 of the shaft 210 is sized to extend through an incision approximately 1 mm in length. In another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision no longer than approximately 2.5 mm. In yet another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision between 1.5 mm and 2.85 mm in length. In some embodiments, the maximum outer diameter of the shaft 210 is no greater than 1.3 mm. The distal end 216 of the shaft 210 can be blunt or sharp. The blunt distal end 216 of the shaft 210 allows for dissection between ocular tissues without penetrating or cutting tissue to locate the stent 105. For example, the distal end 216 of shaft 210 may be configured for blunt dissection between the ciliary body CB and the sclera S (e.g., supraciliary space of the ciliary body), while the scaffold 105 remains completely enclosed within shaft 210 during blunt dissection. In an alternative embodiment, the distal end 216 of shaft 210 has a sharp cutting feature for anatomical application through the scleral wall and implantation into the subconjunctival space. In yet another embodiment, the distal end 216 may have a cutting feature for dissecting and implanting Schrem's canal or for transscleral implantation.

[0098] Shaft 210 can be a submersible tube with a diameter not greater than about 18G (0.050” OD, 0.033” ID), 20G (0.036” OD, 0.023” ID), 21G (0.032” OD, 0.020” ID), 22G (0.028” OD, 0.016” ID), 23G (0.025” OD, 0.013” ID), 25G (0.020” OD, 0.010” ID), 27G (0.016” OD, 0.008” ID), 30G (0.012” OD, 0.006” ID), or 32G (0.009” OD, 0.004” ID). In some embodiments, shaft 210 is a submersible tube with an inner diameter of less than about 0.036” to about 0.009”. This system can incorporate either a 600-micron shaft 210 or an 800-micron shaft 210. Other sizes of the shaft 210 are envisioned in this paper, depending on specific patient conditions and clinical needs.

[0099] In a preferred embodiment, the stent described herein can be formed as a solid strip of material without any lumen, but it should be understood that the stent may also include a lumen. Therefore, the stent typically cannot be delivered via a guidewire like many conventional glaucoma shunts. Furthermore, the stent described herein can be formed from relatively soft tissue, which is more fragile than typical shunts formed from more rigid polymer or metallic materials. Rigid shunts can be implanted, thereby using the distal end of the shunt to create a blunt dissection at the interface between the shunt and the tissue through which it is inserted. The stent described herein is preferably deployed using a retractable cannula-type syringe or inlet tube, which can be retracted once in the appropriate anatomical position, allowing for gentler externalization and precise positioning of the stent.

[0100] The size of shaft 210 can be selected based on the required size of the stent to be implanted. Stent 105 can have a size that substantially fills the lumen 238 of shaft 210 (or the lumen through which the stent is transmitted) such that the stent can be pushed distally through this portion. In some embodiments, the substantially lumen-filling stent is pushed distally without wrinkling or damage. In other embodiments, the substantially lumen-filling stent is pushed distally through shaft 210 by compressing tissue into a plug having a denser construction than the stent when cut from a piece. The dimensional difference or gap between the width and height dimensions of stent 105 and the internal dimensions of the catheter can be up to about 200% of the size of stent 105. The maximum size of the catheter is related to the maximum size 105 of the stent. For example, if the stent width is about 1 mm, the maximum size of the catheter can be 3 mm, resulting in a total gap between the stent width and the outer wall of the catheter that is 200% of the stent width. This gap can be less than 5-10% of the maximum size of stent 105. Generally, the smaller the gap between the stent 105 and the catheter, the better the outcome of advancing the stent 105 through the catheter. If the cross-sectional area of ​​the shaft 210 is greater than 200% of the cross-sectional area of ​​the stent 105, the stent 105 will bend as it is pushed through the shaft 210 for implantation in the eye. The cross-sectional areas of the shaft 210 and the stent 105 are preferably substantially size-matched. The catheter may also be coated with a lubricant or a low-friction material (e.g., Teflon) to improve the advance of the stent 105 through the catheter during deployment.

[0101] The cross-sectional area of ​​shaft 210 may also be smaller than that of stent 105. As described above, stent 105 may be cut to be excessively large relative to the inner diameter of shaft 210, such that stent 105 is compressed, clamped, or otherwise minimally manipulated for delivery through a tube. The stent may be cut to have a first dimension that is excessively large compared to the inner dimensions of shaft 210. The excessively large stent may be prepared within the shaft, for example, by clamping with clamping tool 420, such that stent 105 presents a second, smaller dimension when prepared within the conduit. When stent 105 is deployed in the eye and released from shaft 210, stent 105 may achieve a third dimension close to its original first dimension. Delivery and deployment will be described in more detail below.

[0102] Shaft 210 may, but does not have to, be completely tubular, and its cross-section need not be circular. For example, the cross-section of shaft 210 may be circular, elliptical, square, rectangular, or other geometric shapes. Furthermore, the entire length of shaft 210 does not need to have the same cross-sectional shape or dimensions. For example, the proximal end of shaft 210 may have a first shape and the distal end of shaft 210 may have a second shape. Figures 5A-5BThe cross-section of shaft 210 is shown to be rectangular. The interior cavity 238 of shaft 210 need not be a completely closed passage. For example, shaft 210 may incorporate one or more windows, openings, segmented windows, or walls with one or more discontinuities, such that the interior cavity 238 through shaft 210 is a partially closed passage.

[0103] See you again Figures 3A-3C besides Figures 7A-7C The proximal portion 207 of the housing 200 may include a base 224. The distal region of the base 224 may be coupled to the shaft 210. The proximal region of the base 224 may include a recess 221 configured to receive a sheet 101 of material. The recess 221 may include an inverted V-shaped protrusion 271 that projectes upward from the centerline of the recess 221, pushing upward against the centerline of the sheet 101 of material while allowing the sides of the sheet 101 of material to hang downward into corresponding channels 270 on either side of the centerline. Figures 7A-7C The proximal portion 207 of the housing 200 is shown to be reversibly coupled to a nose cone assembly including a shaft 210 and a nose cone 274.

[0104] The base 224 is configured to mate with the cap 214 and at least partially surround the recess 221 containing the sheet 101 of material. The cap 214 is configured to engage at least a portion of the sheet 101 of material to stabilize the tissue before and during cutting, for example, with the cutting device 300. In one embodiment, the base 224 may include a slot 215 in the upper surface of the base 225, the slot 215 being sized and shaped to receive the cap 214. The cap 214 slides through the slot 215 until the lower surface of the cap 214 abuts against the receiving surface 218 of the base 224. The contact between the lower surface of the cap 214 and the receiving surface 218 of the base 224 ensures that the centerline of the sheet 101 of material within the recess 221 contacts the lower surface of the cap 214 at the protrusion 271 (see [link]). Figure 3C ).

[0105] Cover 214 is an element that can be completely removed from base 224. Figures 3A-3C As shown in the diagram. The cover 214 and the base 224 may optionally be joined together by a hinge or other mechanical feature. For example, the cover 214 may rotate about the pivot axis of the hinge and remain connected to the base 224 even when in a configuration that exposes the recess 221. Figures 7A-7C It is shown that by using cover 214 ( Figure 7A Apply downward pressure to the front end of the cover 214 to open it and apply downward pressure to the rear end of the cover 214 to close it. Figure 7CThe cover 214 can switch between open and closed configurations. For example, the cover 214 can be raised to an open configuration, exposing a recess 221 in the base 224, within which the sheet 101 of material can be positioned. When the cover 214 is positioned back to the closed configuration, the sheet 101 can be compressed and / or tensioned between the cover 214 and the base 224. Once the cover is in the closed configuration (see...), the sheet 101 can be compressed and / or tensioned between the cover 214 and the base 224. Figure 8 Box 200 can then be inserted into 306 of the cutting device 300.

[0106] The cover 214 (or some other element) may be configured to additionally apply a certain amount of tension to at least a portion of the sheet 101 of material, for example, by pulling it outward from the centerline of the sheet 101 of material prior to a cut, as described in U.S. Patent No. 10,695,218, issued June 30, 2020, which is incorporated herein by reference in its entirety.

[0107] The material piece 101 can be inserted into the cassette 200 by the user during surgery. The material piece 101 can be provided in a size approximately the same as the recess 221 within the base 224. The user can trim the material piece 101 before installing it into the recess 221. Alternatively, the cassette 200 can be provided pre-loaded with the material piece 101 located within the recess.

[0108] As mentioned elsewhere in this document, the box does not need to be configured to hold the sheet 101 of material for cutting by the cutting device 300. Instead, the cutting device 300 may be configured to hold the sheet 101 of material for cutting and then transfer the cutting support into the box attached to the cutting device 300. Figures 10A-10C An embodiment of a cassette 200 is shown, which forms a nose cone 274 with a shaft 210 into which a cutting support can be loaded before insertion into the eye. The nose cone 274 can be reversibly coupled to a cutting device 300 and, once loaded with the cutting support, can be removed from the cutting device 300 and coupled to a conveying device 400. The cassette 200 can be positioned relative to the cutting device 300, which is configured to hold a piece 101 of material and cut it into supports 105. The coupling between the cutting device 300 and the cassette 200 allows the longitudinal axis of the distal shaft 210 to be aligned relative to a region of the cutting device, such that the cutting support 105 can be transferred into the distal shaft 210, for example, using a rod or other tool, as will be described in more detail below. The cassette 200, with the distal shaft 210 containing the supports 105 within it, can then be detached from the cutting device 300 and transferred to a portion of the conveying device 400. Therefore, the box 200 does not need to include a portion configured to hold the sheet 101 of material for cutting, but instead includes a transferable portion that can be alternately connected to a region of the cutting device 300 and a region of the conveying device 400. This will be described in more detail below.

[0109] Figure 4A-4J besides Figure 8 An embodiment of a cutting device 300 is shown, which has a cutting assembly for cutting a support from a sheet 101 of material. Figures 14A-14H Various embodiments of the cutting assembly 500 that can be incorporated into the cutting device 300 are illustrated. The cutting device 300 is configured to cut or otherwise prepare bio-derived tissue of a sheet 101 of material having a first profile or shape (e.g., a wider square sheet or a piece of material) to conform to a second profile or shape (e.g., a narrower rectangular strip of material) of an implantable scaffold 105 having the dimensions described herein. Cutting performed using the cutting device 300 described herein can involve guillotine, punching, rotation, sliding, rolling, or pivoting blade cutting movements. In some embodiments, cutting is performed perpendicular to a plane of the sheet of material. In some embodiments, cutting is performed axially along the implant catheter, such that the cutting axis can be aligned, within, or parallel to the implant catheter to allow unobstructed tissue loading and transfer for implantation without manipulating, tearing, or damaging the fragile scaffold tissue.

[0110] As described above, a tissue fixation step precedes the cutting process, in which the bio-derived tissue forming the scaffold is securely fixed between two juxtaposed planes to ensure the tissue is free from wrinkling or deformity and that the subsequent cut is dimensionally accurate. Fixation may optionally provide compression and tension or stretching of the tissue in at least one plane to ensure clean tissue cutting. The cutting assembly 500 may hold the piece 101 of material prior to cutting, or the piece 101 of material may be held within the area of ​​the tissue cassette 200 prior to being cut by the cutting assembly 500. In some embodiments, the cutting device 300, combined with the lid 214 of the cassette 200, may incorporate front-to-back capture such that the material 101 to be cut remains fixed in the z-plane, thereby preventing movement before the tissue engages with the cutting member 312.

[0111] The cutting can be performed within a path or conduit formed within the cassette 200. Thus, the implant 105 cut from the sheet of material 101 can be positioned simultaneously or subsequently within a conduit for delivery, or the implant 105 can be aligned with a conduit for delivery, so that the cut implant 105 can be delivered to the eye through the conduit without needing to be transferred from the cassette 200.

[0112] As an example, a piece 101 of material held in the recess 221 of the box 200 is cut by the cutting member 312 of the cutting device 300, forming a cutting bracket 105 in the recess 221 of the box. This cutting bracket can be pushed distally from the recess 221 into the cavity 238 of the shaft 210 of the box 200, so that it can be deployed in the eye without having to remove the cutting bracket 105 from the box 200 or at least the distal portion 205 of the box 200.

[0113] about Figures 4A-4B besides Figure 6 The cutting device 300 may include a base 302 having a distal portion 305 and a proximal portion 307. The distal portion 305 may include a distal opening or a receiver 306, sized and shaped to receive the proximal portion 207 of the cassette 200. The inner diameter of the receiver 306 may be sufficient to receive the external dimensions of the proximal portion 207, allowing the proximal portion 207 to be inserted into the receiver 306 a certain distance. A cover 214 of the cassette 200 is positioned within a slot 215 to hold a piece of material 101 within a recess 221. The upper surface of the cover 214 may extend above the upper surface of the base 224, thus fixing the external dimensions of the proximal portion 207. In other words, the external dimensions of the cassette 200 are fixed and can only be inserted into the receiver 306 of the cutting device 300 in a single orientation (e.g., the upper cover 214).

[0114] The cutting device 300 may further include a cutting assembly 500 having a cutting member 312 configured to cut pieces 101 of material within the recess 221 of the box into supports 105 (see [link]). Figure 4C The construction of the cutting member 312 can vary. In such a construction, the cutting member 312 may include at least a first blade 344a and a second blade 344b spaced apart from the first blade 344a. When the housing 200 is mounted within the receptacle 306 of the cutting device 300, the first and second blades 344a, 344b can be positioned above the sheet of material 101. Actuation of the cutting member 312 causes the first and second blades 344a, 344b to be pushed toward the sheet of material 101 through which the material thickness is cut, thereby forming a support 105. The blades 344a, 344b may have a width along the longitudinal axis A of the housing 200 sufficient to cut the full length of the sheet of material 101. The distance between the blades 344a, 344b can be designed to achieve the width required for the cutting support 105.

[0115] In some embodiments, blades 344a and 344b can be positioned above the sheet 101 of material to be cut, and corresponding lower blades 345a and 345b can be positioned below the sheet 101 of material. Therefore, when blades 344a and 344b are pushed downward toward the sheet 101 of material, they push the sheet 101 of material toward the lower blades 345a and 345b, so that the corresponding upper and lower blades completely cut through the material 101 at two locations, thereby creating a support 105.

[0116] The cutting member 312 can be actuated by a user to move the blade. The cutting device 300 may include one or more handles 343 movably connected to the base 302 to actuate the cutting member 312. The handles(one or more) 343 may be connected via a hinge 317 such that the handles 343 rotate relative to the base 302 about a pivot axis P of the hinge 317. For example, the handles 343 may be lifted to pivot as follows: Figure 4A The opening structure is shown, and it rotates back around the pivot axis P as shown. Figure 4B The cut structure shown.

[0117] When the handle 343 is raised to the open position and the cutting member 312 is positioned away from the cutting position, the box 200 can be inserted into the receiving seat 306 of the cutting device 300. Figure 4D-4E As best shown, the cassette 200 can be slid into the housing 306 to position the recess 221 holding the material piece 101 below the upper blades 344a, 344b and above the lower blades 345a, 345b. A cover 214 holding the material piece 101 within 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 aligns with the protrusion 271 of the recess 221 and holds the material piece 101 therebetween. When the cassette 200 is fitted with the cutting device 300, the upper portion 220 of the cover 214 can slide above the upper blades 344a, 344b. The lower portion 222 of the cover 214 is sized to slide between the upper blades 344a, 344b when the cassette 200 is inserted into the housing 306 of the cutting device 300. Figure 4D The upper blades 344a and 344b are shown to be spaced apart from the lower blades 345a and 345b, with the narrow lower portion 222 of the cover 214 located between them. Figure 4E The handle 343 is shown rotating downwards back to the cutting configuration, and the upper blades 344a and 344b are pushed downwards toward the material sheet 101 and toward the lower blades 345a and 345. The material sheet 101 is cut by the corresponding upper and lower blades, thereby forming a support 105. The distance between the upper and lower blades determines the width of the support 105 cut from the material sheet 101.

[0118] The handle 343 can be opened relative to the base 302 in any number or orientation. For example, the pivot P of the hinge 317 can be substantially perpendicular to the longitudinal axis of the base A. In this embodiment, the hinge 317 can be positioned at the distal end of the base 302 such that the handle 343 is hinged open by rotating upward and toward the distal end of the base 302. The upper blades 344a, 344b can be spring-loaded, making them easily return to the open configuration as the handle 343 is lifted or released.

[0119] Once the support 105 is cut, it is received on all sides by the housing 200 and the cutting member 312, thereby forming a complete enclosure or support cutting chamber for the support 105 within the assembly of the cutting device 300 and the housing 200. For example, the bottom and top of the support cutting chamber may be formed by the lower portion 222 of the cover 214 and the protrusion 271 of the recess 221. The walls of the support cutting chamber may be formed by the upper blades 344a, 344b and the lower blades 45a, 345b of the cutting member 312. Together, the walls of the support cutting chamber may be rectangular to help constrain and guide the pusher 320 of the cutting device 300, which is advanced to push the support 105 distally from the support cutting chamber into the cavity 238 of the shaft 210. In one embodiment, the cross-section of the support cutting chamber may be at least partially arcuate or circular. The upper and lower surfaces of the cutting chamber may be curved or non-planar. As an example, the lower portion 222 of the cover 214 can be recessed, thus forming a concave shape that creates an arched top for the cutting chamber. The bottom of the cutting chamber, formed by the protrusion 271, can be combined with a corresponding concave shape. The arched top and concave bottom of the cutting chamber reduce the amount of open space created relative to the inner wall of the shaft around the cutting support 105, which could otherwise cause the push rod to deviate from its track or allow the cutting support 105 to deflect away from the desired path during deployment. Minimizing the space within the shaft relative to the trephine support 105 improves the propulsion of the support 105 through the device. The cutting support 105 can also have a cross-sectional shape that more closely matches the cross-sectional shape of the delivery conduit through which the support 105 must advance. The corresponding shape eliminates excess space on the upper and lower sides of the cutting support 105 relative to the conduit. This, in turn, provides better guidance for the pusher 320 to advance the cutting support 105 toward the distal end of the shaft. The support 105 can also be cut too large relative to the conduit size, as discussed elsewhere herein, and compressed, clamped, or otherwise manipulated within the conduit prior to deployment.

[0120] Once the bracket 105 is cut, it can be aligned axially with the inner cavity 238 of the shaft 210 of the box 200. Figure 4F-4G besides Figure 4H-4JThe cutting device 300 is shown to include a pusher 320 configured to slide distally relative to the base 302 into the proximal region of the cartridge 200 to advance the cutting stent 105 from this fully enclosed position along the implantation catheter into the lumen 238 of the shaft 210. The pusher 320 in... Figure 6 The implementation details are not visible. However, the base 302 may include an actuator 304, such as a turntable, button, slider, or other input, operatively coupled to the pusher 320 to move the pusher 320 distally relative to the base 302 upon actuation. Any of the various user actuators 304 herein is considered to move the pusher 320 to position the support 105 relative to the cavity 238. This preparation step of the pusher 320 of the cutting device 300 ensures that after the cassette 200 is removed from the cutting device 300 and before the cassette 200 is coupled to the conveyor 400, the cutting support 105 is held within a completely enclosed space on all sides (i.e., the area of ​​the shaft 210).

[0121] Figure 4H It is shown that when the handle 343 is pushed down toward the base 302 (e.g., the blade 344 is positioned in the cutting configuration relative to the implant 105), the pusher 320 of the cutting device 300 can be pushed distally through the base 302. Figure 4I A pusher 320 is shown, ready to engage the bracket 105 within the recess 221 on the proximal end. Figure 4J The image shows that the pusher 320 has advanced the stent 105 distally into the cavity 238 of the shaft 210 of the housing 200. As described above, except for the upper cover 214 and the lower protrusion 271, the blade 344 creates a complete enclosure on all sides for cutting the stent 105, preventing the stent 105 from bending within the cavity 238 during this distal advancement into the cavity 238. The conduit in which the stent 105 is held is dimensionally matched (or undersized) to the external dimensions of the stent being implanted, thereby preventing bending and wrinkling as the stent 105 is pushed into the ready position.

[0122] The bracket 105 can be pushed into the distal region 212 of the shaft 210 and the box 200 is removed from the cutting device 300. Once the cutting device 300 and the box 200 are separated from each other, the box 200 is ready to be loaded by the conveyor 400 for insertion of the bracket 105 into the eye.

[0123] The material sheet 101 can be cut and loaded into the shaft 210 of the cassette 200 in various ways. As discussed elsewhere, the material sheet 101 can be cut to a size substantially the same as the conduit through which it will be conveyed. Preferably, the material sheet 101 can be cut to a size slightly larger than the conduit through which it will be conveyed, such that the support 105 is compressed and packaged within the conduit, allowing for easier passage through the lumen 238. The cutting can be as described above regarding... Figures 4A-4E Proceed as described. Alternatively, the following text and related information can be used. Figures 14A-14H Other cutting components 500 described herein are used to perform the cutting of material into pieces and transfer them to the shaft 210. The cutting component 500 described herein may form part of the tissue cassette 200, the cutting device 300, or the conveying device 400. Preferably, the cutting component 500 is part of the cutting device 300. The cutting device 300 may be coupled to at least a portion of the cassette 200, such as the nasal cone assembly 274, wherein the distal shaft 210 extends from the nasal cone 275, such that the cutting support 105 can be prepared within the shaft 210 for conveying using the conveying device 400. The cassette 200 may include a proximal portion 207 configured to hold pieces of material for cutting, as in... Figure 2 , 3A As shown in -3C or 7A-7C, or including a removable nose cone 274 and shaft 210, as... Figures 9A-9D , Figure 10A As shown, it does not include the proximal portion 207 for holding the pieces of material. The box 200, whether or not configured to hold pieces of material for cutting, can be a portable component designed to be coupled to the cutting assembly, prepared with a cutting support, removed from the cutting assembly, and coupled to a conveyor to deploy the cutting support in the eye.

[0124] Figure 14AOne embodiment of the cutting assembly 500 is shown. The cutting assembly may be part of a cutting device 300 configured to engage with a cassette. The cutting assembly 500 can cut pieces 101 of material, which may be held within the cassette or within the area of ​​the cutting assembly 500. A cutting support may be transferred from the cutting assembly 500 to a distal shaft 210 of the cassette 200 for axial delivery into the eye. The cutting assembly 500 may incorporate a cutting die 511 positioned 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 may rotate 90 degrees relative to the base 509 from a first position to a second position. When the movable member 505 is rotated to its second position, the piece 101 of material may be placed against the cutting surface 513. The cutting die 511 may press the piece 101 of material against the cutting surface 513. Pushing the cutting die 511 toward the cutting surface 513 allows the material slab 101 to be cut through in two locations, as described elsewhere herein. Excess tissue can be removed from the cutting surface 513, and the movable member 505, still holding the cutting support 105 on its cutting surface 513, rotates toward the first position. This arranges the cutting support 105 on the cutting surface 513 within the path of the slot 507, allowing the clamping tool 517 or other member to load the cutting support 105 into the slot 507. The slot 507 may have an end region 508 that, when the housing 200 is coupled to the cutting device 300, is aligned with the longitudinal axis A of the distal shaft 210. The end region 508 may have a circular cross-sectional shape similar to that of the distal shaft 210. The cutting support 105, positioned within the end region 508, can then be pushed into the cavity of the distal shaft 210, thus preparing it for transport. The dimensions of the slot 507 and / or the distal region 508 may be smaller than the dimensions of the cutting bracket 105, such that the advance of the clamping tool 517 into the slot 507 causes the bracket 105 to be compressed and clamped into a plug. Once the cutting bracket 105 is positioned within the distal axis 210 of the cartridge 200, the cartridge 200 can be removed from the cutting device 300 and transferred to the conveyor 400 for deployment in the eye.

[0125] Figure 14B This illustration shows one embodiment of the interconnected cutting assembly 500 for cutting sheet pieces 101 of material and transferring the cutting support 105 for conveying. Figure 14ASimilar to the previous embodiment, the cutting assembly 500 may be part of the cutting device 300, which is configured to engage with the cassette. A piece of material may be held within the cutting area of ​​the cassette, or may be held by a part of the cutting assembly 500. A cutting die 511 may be inserted through a compression pad 515 to cut the piece of material 101. The piece of material 101 may be positioned against a cutting surface 513. The cutting surface 513 need not be part of a movable member as in the previous embodiment, but may be at least a portion of the base 509. The piece of material 101 may be compressed between the cutting surface 513 of the base 509 and the compression pad 515. The cutting die 511 may advance through the compression pad 515 such that the blade of the cutting die 511 cuts through the piece of material 101 in two locations. After the piece of material 101 is cut, excess tissue may be removed and the pressure applied by the compression pad 515 may be released. The cutting die 511 may include a spring 516 to return it to its initial position, and the pressure pad 515 and the cutting die 511 no longer exert pressure on the cutting holder 105. The cutting holder 105 may be positioned relative to a slot 507 in the base 509, so that the clamping tool 517 can push the cutting holder 105 through the slot 507 toward the end region 508. As discussed elsewhere, the cutting holder 105 may be oversized relative to the size of the slot 507, so that pushing the holder into the conduit will compress and clamp the holder 105 for delivery. The slot 507 may have an end region 508 that is aligned with the longitudinal axis A of the distal shaft 210 when the cassette is coupled to the cutting device 300. The cutting holder 105, positioned within the end region 508, can then be pushed into the distal shaft 210, thus preparing it for delivery. The cassette containing the cutting holder 105 can now be removed from the cutting device 300 and transferred to the delivery device 400 for deployment in the eye.

[0126] Figure 14CAn interrelated embodiment of a cutting assembly 500 is shown, which cuts a sheet of material 101 and transfers a cutting support 105 for transport. The cutting assembly 500 may additionally incorporate a movable stop 520 positioned between the sheet of material 101 and a slot 507 through which the cutting support 105 will be advanced. A compression pad 515 and a cutting die 511 press the sheet of material 101 against the cutting surface 513 of the base 509. The sheet of material 101 may be enclosed between the lower cutting surface 513, the distal movable stop 520, and the upper compression pad 515. The cutting die 511 may include a single blade and is advanced through the compressed sheet of material 101 to cut the sheet in a single location, thereby producing the support 105. The cutting die 511, compression pad 515, and movable stop 520 can retract away from the cutting bracket 105, allowing the clamping tool 517 to push the cutting bracket 105 distally into the slot 507 for transport. When the cartridge is coupled to the cutting device 300, the end region 508 of the slot 507 can be aligned with the longitudinal axis A of the distal shaft 210. The cutting bracket 105 located in the end region 508 can then be pushed into the distal shaft 210, thus preparing it for transport as described elsewhere. Figure 14I Showing relative to Figure 14C The nasal cone assembly 274 is arranged in the cutting assembly 500. The longitudinal axis A of the distal shaft 210 of the nasal cone assembly 274 can be aligned with the end region 508 of the slot 507, so that the clamping tool 517 can push the cutting support 105 into the shaft 210. Once the cutting support 105 is clamped into the cavity 238 of the shaft 210, the nasal cone assembly 274 can be removed from its association with the cutting assembly 500 and transferred to the transport device 400 for deployment in the eye.

[0127] The position of the movable stop 520 relative to the cutting blade of the die 511 can be adjusted to achieve different support widths. For example, the movable stop 520 can move toward the individual blade of the cutting die 511 to reduce the support width, and can move away from the cutting die 511 to increase the support width. The position of the movable stop 520 relative to the cutting die 511 can be selected by the user, for example, via a turntable or other user interface that allows incremental adjustment. The turntable range can be between about 0.6 mm and about 1.9 mm, and may include markings arranged in 1 / 4 to 1 / 16 thread. As described elsewhere herein, the cutting die 511 of the cutting assembly 500 can be attached to a lever, handle, or other actuator 343 to advance the individual blade through a piece 101 of material held against the cutting surface 513 by a pad 515 when the width is selected. In one embodiment, the cutting surface 513 can be 1 / 16” 90A silicone.

[0128] Figures 15A-15B A cutting device 300 with a cutting assembly 500 is shown. The cutting device 300 may include a handle 543 movably coupled to a base 509 to actuate the cutting assembly 500. For example, the handle 543 is configured to raise and lower the cutting die 511 relative to a cutting surface 513 of the base 509. The cutting surface 513 may include a recess 544 sized to hold a piece of material (not shown). The cutting surface 513 may be movable relative to the base 509 to expose the recess 544 in order to position a piece of material 101 within the recess 544. The cutting device 300 may incorporate an actuator 545, such as a turntable, button, slider, switch, or other type of actuator configured as described above to adjust the position of the blade 511 relative to the cutting surface 513. Actuator 545 can move base 509 left and right via a threaded screw or other mechanism to change the position of the piece 101 of material held within recess 544 relative to cutting die 511, and thereby change the width of the support cut from the piece. Alternatively, actuator 545 can move die 511 relative to recess 544 to change the width of the support. Cutting device 300 can be combined with stage 546, configured to move relative to base 509, for example by sliding, rotating, or lifting off base 509. In some embodiments, stage 546 can slide relative to the underlying base 509 in a single plane while remaining at least partially attached to base 509. Alternatively, stage 546 can be completely removed from base 509. Moving stage 546 relative to base 509 exposes recess 544 from below the device area where cutting die 511 and handle 543 are located. This allows pieces to be loaded within recess 544 without obstructing the user's view or physically hindering access. The cutting device 300 can be a standalone cutter and does not require the combination of a compression or holding mechanism or a transfer mechanism. Instead, the cutter 105, after being cut by the cutting assembly 500, can be manually transferred to another tool for preparing the cutter 105 for deployment via the axis.

[0129] Figure 14DThis illustration shows one embodiment of an interconnected cutting assembly 500 for cutting a sheet of material 101. The cutting assembly 500 may include a paper punching type cut. A sharp, pointed or protruding edge 525 may protrude from a cutting surface 513. The sharp edge 525 may surround a hole 527 through the cutting surface 513, which directly enters a slot 507 in the base 509. The sheet of material 101 may be positioned against the cutting surface 513 above the hole 527 and against the sharp edge 525. A punch 511 may be pushed from above against the sheet of material 101, causing the sheet of material 101 to be cut by the sharp edge 525, and a cutting bracket 105 is pushed by the punch 511 through the hole 527 into the slot 507. The cutting bracket 105 can then be arranged within the slot 507 such that the pusher ( Figure 14D (Not shown) The cutting bracket 105 can be pushed through the slot 507 toward the end portion 508. The end portion 508 of the slot 507 aligns the cutting bracket 105 with the longitudinal axis A of the distal axis 210, thereby allowing the bracket to be pushed into the distal axis 210, thus preparing it for transport. The cassette can be removed from the cutting device 300 and transferred to the transport device 400 for deployment in the eye.

[0130] Figure 14E An interconnected embodiment of a cutting assembly 500 for cutting a piece of material 101 is shown. The cutting assembly 500 may also incorporate a money plunger-type cut. The piece of material 101 may be positioned above a slot 507 in a base 509, and a cutting die 511 is pushed against the material 101 from above, such that the cutting edge of the die 511 can cut through the piece of material 101 at two locations to cut the length of a cutting support 105. A clamping tool 517 may be advanced through an orifice 529 in the die 511 to drive the cutting support 105 into the slot 507, thereby pushing it to the end region 508 of the slot 507. The clamping tool 517, or an additional compression tool 421, may be advanced through the orifice 529 in the die 511 to compress the cutting support 105 within the end region 508 of the slot 507, to press it firmly and align the cutting support 105 with the distal axis 210, thus preparing it for transport. The box can be removed from the cutting device 300 and transferred to the conveying device 400 for deployment in the eye.

[0131] Figure 14F-1 and Figure 14F-2An interconnected embodiment of a cutting assembly 500 for cutting a piece of material 101 is shown. The cutting assembly 500 can be combined with a clamp-like tool 530 to hold the piece of material 101. A surgical scalpel or other cutting tool 535 can be used to trim the piece of material 101 held by the clamp 530 to a certain length. The clamp 530 holding the cutting support 105 can be arranged relative to the base 509, and the clamping pressure of the clamp 530 is released. A clamping tool 517 can be advanced through the clamp 530 to push the cutting support 105 from the clamp 530 into a slot 507 of the base 509 for compressing and clamping the cutting support 105 for delivery as described above.

[0132] Figure 14G An interconnected embodiment of a cutting assembly 500 for cutting a piece of material 101 is shown. The cutting assembly 500 may incorporate a plunger 511 configured to compress the piece of material 101 within a transfer slot 537 of a transfer base 539. The piece of material 101 may be trimmed to a specific size using a surgical scalpel or other cutting tool 535. The cutting support 105 within the transfer slot 537 may be transferred by attaching the transfer base 539 to a base 509 having a defined slot 507 in such a way that the transfer slot 537 is aligned with the slot 507 so that the cutting support 105 is compressed and loaded using a clamping tool 517 for deployment.

[0133] Figure 14H An interconnected embodiment of a cutting assembly 500 for cutting sheet 101 of material is shown. The cutting assembly 500 may incorporate a rotating cylinder 540 configured to cut and arrange a cutting support 105 relative to a slot 507 in a base 509 for loading and compressing the support 105 for transport. The rotating cylinder 540 may incorporate an internal slot 542 for receiving at least a portion of the sheet 101 of material. Rotation of the cylinder 540 trims excess material extending beyond the slot 542 in the cylinder 540. The cutting support 105, trimmed to a suitable length within the slot 542 of the cylinder 540, is then arranged relative to the slot 507 in the base 509 for loading and compressing for transport.

[0134] The cutting support 105, loaded and compressed for transfer, can be positioned within at least a portion of the housing 200, for example, within the cavity 238 of the shaft 210. At least a portion of the housing 200 can be removed from the cutting device 330 and engaged with the transfer device 400 for deploying the support 105 from the housing 200 into the eye. The aforementioned compression and transfer of the cutting support 105 with respect to the cutting assembly 500 prepares the cutting support 105 for transfer without removing it from the housing 200.

[0135] The cassette 200 is described herein as configured to engage with a cutting device 300 (which has a cutting assembly 500 for cutting pieces 101 of material) and then be removed from engagement with the cutting device 300 so that it can be engaged with a conveying device 400. This relationship may include removing and re-engaging the entire cassette 200 or only a portion of the cassette 200, such as only the nose cone assembly 274 (e.g., nose cone 275 and shaft 210). Both arrangements are considered here. The nose cone assembly 274 may be simply referred to herein as cassette 200. When cassette 200 is described as being removed from the cutting device 300, this description relates to either only the nose cone assembly 274 being removed from the cutting device 300 or the entire cassette 200 being removed from the cutting device 300. When cassette 200 is described as being configured to engage with the conveying device 400, this description relates to either only the nose cone assembly 274 being engaged with the conveying device 400 or the entire cassette 200 being engaged with the conveying device 400. The connection between box 200 and another component of system 100 can be the entire box 200 or just a part of box 200, such as nose cone assembly 274.

[0136] A piece of material 101 can be placed within a portion of a cassette 200 for cutting, or a piece of material 101 can be placed within a portion of a cutting device 300 for cutting by a cutting assembly 500 and a cutting support 105 transferred to a cassette 200 (or only a portion of a cassette 200, such as a nose cone assembly 274). The cutting support 105 can be transferred to a cassette 200 using components of the cutting assembly 500, after which the cassette 200 is detached from the cutting device for connection to a conveying device. The piece of material 101 can be placed within an area of ​​the cutting assembly 500 for cutting, and then the cutting support 105 can be manually transferred from the cutting assembly 500 to be pressed within a conveying shaft 210. The cutting support 105 can be transferred from the cutting assembly 500 using a separate device, including manual transfer. In one embodiment, the system includes a cutting device 300 having a cutting assembly 500. The cutting bracket 105 from the cutting assembly 500 can be manually transferred (e.g., by clamps) to a transfer device with a clamping tool 517 to clamp the cutting bracket 105 into the distal shaft 210. The distal shaft 210, in which the cutting bracket 105 is clamped, can then be coupled to a transfer device 400 to deploy the cutting bracket 105 into the eye. The system can have separate cutting, transfer, and conveying devices, rather than integrated ones or more. Figures 14A-14H The cutting assembly 500 shown can be part of the cutting device. The transfer component of the cutting assembly 500 can be integrated with the cutting device or can be a separate transfer device.

[0137] System 100 may include a conveying device 400 configured to engage at least a portion of a box 200 holding the cutting support 105. In some embodiments, the entire box 200 having the cutting support 105 is removed from the cutting device 300 and connected to the conveying device 400 (see [link to documentation]). Figure 2 Engagement. In associated embodiments, a portion of the box 200, where the cutting support 105 is positioned, is removed from the cutting device 300 and engaged with the conveying device 400 (see [link]). Figure 6 , 9A -9D).

[0138] exist Figures 5A-5B In the embodiment shown, the box 200 holding the cutting bracket 105 can be removed and loaded into the conveyor 400. Figure 5C-5F The diagram illustrates loading a tissue cassette 200 within a delivery device 400 and deploying a cutting stent 105 using the delivery device 400. The delivery device 400, together with the cassette 200, can be used to deliver the stent 105 to the implantation site, such as via an internal delivery pathway. This allows for stent loading and deployment without having to remove the cutting stent 105 from its position within the cassette 200 to load it into the delivery device 400. At least a portion of the cassette 200 (e.g., the proximal portion 207 of the cassette 200 or the region of the nasal cone assembly 274) can be held by the delivery device 400, and the distal portion 205 of the cassette 200 can be inserted into the eye.

[0139] The delivery device 400 may include a proximal handle 405 and a distal region 410. The proximal handle 405 is sized and shaped to be gripped by a user with one hand, and the distal region 410 defines an attachment mechanism 425, such as a receiver 412 sized to engage at least a portion of the cassette 200. In one embodiment, the receiver 412 may be sized to receive at least a length of the proximal portion 207 of the cassette 200 (see [link to previous embodiment]). Figure 5C In one interconnected embodiment, attachment mechanism 425 may be combined with another male-to-female attachment mechanism, such as bayonet connection 413 (see [link]). Figures 10A-10CAs mentioned above regarding the cutting device 300, the attachment mechanism 425 may be keyed, allowing the box 200, with the cover 214 positioned on the base 224, to be received within or otherwise engaged with the attachment mechanism 425 in a single orientation. When the box 200 is engaged with the attachment mechanism 425 of the handle 405, the shaft 210 of the box 200 extends outward from the handle 405 in a distal direction. The keying feature of the attachment mechanism 425 prevents attachment in an incorrect orientation. The attachment mechanism 425 may also provide the user with a secure connection with tactile feedback to indicate when the connection is fully engaged. The dimensions of the attachment mechanism 425 are also designed to ensure that the cavity 238 of the shaft 210 aligns with the internal mechanisms of the conveying device 400, such as the push rod 420.

[0140] Figures 5A-5C The attachment mechanism 425 may be a reservoir 412, the depth of which is sufficient to accommodate the length of the proximal portion 207 of the box 200, while the shaft 210 remains outside the reservoir 412. A flexible hook 422 may extend into at least a portion of the reservoir 412 (see [link to relevant documentation]). Figure 5C The distal end 424 of hook 422 can be received within a correspondingly shaped pawl 272 near the proximal region of tissue cassette 200. As cassette 200 slides within receiver 412, the distal end 424 of hook 422 can slide through the proximal end 207 of cassette 200 and engage within pawl 272. The flexibility of hook 422 allows it to be pushed upward as the distal end 424 advances through a first region of cassette 200 and bends downward as the distal end 424 advances further, thereby engaging pawl 272 (see [link]). Figure 5D The spring-loaded hook 422, which engages with the pawl 272, can provide a tactile and / or audible "click" sound to notify the user that the box 200 has been fully installed within the conveyor 400, is reserved, and is ready to be conveyed to the conveyor bracket 105.

[0141] One or more actuators 415 may be positioned on the area of ​​the handle 405. The actuator 415 may also be operated by a user with one hand, such as with the thumb or finger. The construction of the actuator 415 may vary. For example, the actuator 415 may include any of the various knobs, buttons, sliders, dials, or other types of actuators (described in more detail below) that constitute one or more components of the motion transmission device 400.

[0142] The conveying device 400 may include a clamping tool 420 configured to be moved by one or more actuators 415. Once the distal end of the shaft 210 reaches the desired position, the clamping tool 420 can be used with the cassette 200 to convey the bracket 105 from the cassette 200. The size and shape of the clamping tool 420 may be complementary to the internal dimensions of the shaft 210. For example, if the shaft 210 of the cassette 200 has a rectangular cross-sectional shape, the cross-section of the clamping tool 420 may be rectangular. This allows the clamping tool 420 to effectively push the cutting bracket 105 through the cavity 238 of the shaft 210.

[0143] Before attaching the tissue cassette 200 to the conveyor 400, the clamping tool 420 can be fully retracted in the proximal position, so that the clamping tool 420 does not interfere with the loading of the cassette 200. Once the cassette 200 is installed and held within the conveyor 400, as... Figure 5D and Figure 9B As shown, the clamping tool 420 can be advanced distally through the proximal port in the housing 200 and enter the cavity 238 of the shaft 210 (see Figure 238). Figure 5E and Figure 9C In some embodiments, the clamping tool 420 may be advanced through the cavity 238 and exit from the distal opening 230 of the cavity 238 to deploy the bracket 105. In other embodiments, the clamping tool 420 is advanced to a distal position near the proximal end of the bracket 105 within the cavity 238, and the shaft 210 retracts proximally while the clamping tool 420 remains stationary to deploy the bracket 105 (see [link to documentation]). Figure 5F and Figure 9D ).

[0144] The shaft 210 can be retracted proximally by the movement of the housing 200 relative to the conveyor 400 in the proximal direction while the clamping tool 420 remains stationary, so as to deploy the stent 105 within the eye (see...). Figure 5F and Figure 9D Therefore, the clamping tool 420 can act as a stop to prevent the stent 105 from following the shaft 210 during its retraction. As a result, the stent 105 disengages from the shaft 210 and remains within the tissue. In other embodiments, both the cartridge 200 and the clamping tool 420 are movable to allow the stent to be deployed from the shaft 210.

[0145] In some embodiments, the clamping tool 420 may be coupled to a first actuator 415 and the cassette 200 may be coupled to a second actuator 415. The first and second actuators 415 may be sliders, buttons, or other configurations or combinations of actuators configured to advance and retract their respective components. The first actuator 415 coupled to the clamping tool 420 may retract proximally, such that the clamping tool 420 is in its proximal position when the cassette 200 is engaged by the attachment mechanism 425 of the delivery device 400. A user can advance the first actuator 415 to push the clamping tool 420 distally to advance the support 105 within the cavity 238 of the cassette 200 toward the distal opening 230 of the shaft 210. After the cutting support 105 is prepared into its distal position within the cavity 238, the shaft 210 of the cassette 200 can be used to dissect eye tissue until the target location is reached. Once the shaft 210 is in place to deploy the support 105 in the eye, the first actuator 415, coupled to the clamping tool 420, can be held in this distal position, and the second actuator 415 is actuated (e.g., by retracting a slider or pushing 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 relative to the clamping tool 420 deploys the support 105 from the lumen 238 in the anatomical structure.

[0146] Figure 5E A cassette 200 is shown, mounted within a housing 412 of a conveyor 400, such that a space exists between the end of the housing 412 and the nearest end of the cassette 200. The depth of this space defines the maximum retractable distance 200 of the cassette. A support 105 is positioned near the distal opening 230 relative to the cavity 238, and a clamping tool 420 is advanced to its distal position such that the distal end of the clamping tool 420 abuts against the proximal end of the support 105. The distal end 424 of the hook 422 remains within the pawl 272 and the second actuator 415 is not yet actuated. The proximal end 426 of the hook 422 is coupled to a spring 430. When the second actuator 415 is stationary before actuation, the hook 422 is pushed distally into the first configuration. As the hook 422 is pushed distally into the 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 second actuator 415 is actuated (e.g., pushed down), the spring 430 is released and pushes the proximal end 426 of the hook 422 toward the proximal end of the handle 405. The hook 422 moves proximal and drags the box 200 along with it—which is engaged with the hook 422 due to the engagement of the distal end 424 of the hook 422 within the pawl 272. The distance the hook 422 moves proximal thus retracts the box 200 deeper into the receiver 412. The clamping tool 420 can remain stationary during the retraction of the box 200. The relative movement 420 between the shaft 210 and the clamping tool 420 deploys the bracket 105 from the cavity 238 (see...). Figure 5F ).

[0147] It should be understood that the additional distal movement 420 of the clamping tool can be used to assist in the deployment of the stent 105 from the lumen 238. It should also be understood that the advancement of the clamping tool 420 and the retraction of the cartridge 200 can be controlled as described above by a dual actuator 415 or by a single actuator 415 capable of moving both the pusher and the cartridge 200 depending on the degree of actuation. Furthermore, during the process of using the clamping tool 420 as a plunger, the shaft 210 can be used to inject a viscous material, such as a viscoelastic material. The method of implantation and delivery of the stent 105 is described in more detail below.

[0148] Figure 11A-11C The steps for deploying a support are illustrated by using a first actuator 415a (which may be a slider in this case) of a delivery device 400 to move a pusher from a first loading position (fully retracted) to a second ready position (at least partially advanced). The first loading position retracts the pusher away from the distal region of the delivery device 400, thereby allowing the nasal cone assembly 274 (or the entire housing 200) to be coupled to the delivery device 400. The second ready position advances the pusher toward the distal end of the delivery device 400 to advance the cutting support 105 through the cavity 238 of the shaft 210. Preferably, the pusher is advanced to the second ready position before the shaft 210 is inserted through the cornea. The delivery device 400 may additionally incorporate a movable guard 432, which is arranged to prevent the user from accidentally pushing the slider past the second ready position. The guard 432 may be pushed down toward the housing of the delivery device such that the second actuator 415b is covered by the guard 432, thereby preventing the second actuator 415b from being accidentally activated. The protective device 432 has a certain length such that it extends over at least a portion of the slider track, thereby blocking the second actuator 415b. Figure 11B In addition to preventing the first actuator 415a from moving further distally, the protective device 432 can be rotated upwards to expose the second actuator 415b without obstruction once the bracket 105 is advanced to the ready position and prepared for deployment in the eye. The first actuator 415a can then slide freely further distally along the track, and the second actuator 415b can be depressed. Figure 11C The protective device 432 may also be completely removed from the device 400, or the device 400 may not include any protective device 432. The housing of the device 400 may include one or more markings 434 intended to provide feedback to the user regarding the position of the clamping tool 420 via the shaft 210. As described elsewhere herein, advancing the clamping tool 420 to one or more positions relative to the housing may also provide tactile feedback to the user.

[0149] Figure 12A-12DThe conveying device 400 is shown in cross-section before and after the pusher rod 420 is advanced to the second position. Once the nose cone assembly 274 is attached to the conveying device 400, the first actuator 415 and the clamping tool 420 can be advanced from the initially retracted first position to the second position. The first actuator 415a and the clamping tool 420 can be advanced to the second position, resulting in the clamping tool 420 being inserted into the cavity 238 behind the material to be conveyed (e.g., the cutting bracket 105). The guard 432 prevents the first actuator 415a from sliding past the second position. The second position is designed to position the leading face of the clamping tool 420 at a predetermined distance (e.g., 6 mm) from the distal end of the shaft 210. Once the user has created the desired slit and is ready to convey material from the cavity, the clamping tool 420 can be advanced to its third, foremost position (where the guard 432 is not obstructed, or is otherwise removed from the device 400 or is not present). The second actuator 415b can be engaged to release the material from the shaft 210. As described elsewhere herein, the second actuator 415b can retract the shaft 210 while the clamping tool 420 remains fixed, ultimately releasing the bracket 105 from the cavity. The nose cone assembly 274 retracts and the clamping tool 420 remains fixed.

[0150] The delivery device 400 and the box 200 (or the nose cone assembly 274) can be disposable devices or can be sterilized and reused. Figures 13A-13B A reset mechanism 436 is shown, which allows the deployment structure to be reset and the transfer device 400 to be reused. Activating the reset mechanism 436, for example by sliding a button forward, returns the deployment structure to a standby position. The reset mechanism 436 can also be performed by pulling the nose cone assembly 274 or bayonet connector 413 of the transfer device 400 distally until the second actuator 415 returns to its initial standby position. If necessary, the nose cone assembly 274 can be removed from the transfer device 400, and additional material can be loaded into the shaft 210, as described elsewhere herein. The transfer device 400 can be provided in an actuated or non-standby state, and the user equips the device during use.

[0151] A nasal cone assembly transferable between a delivery device and a cutting device can be mounted relative to the main assembly of the cutting device. Tissue pieces can be cut by the cutting device and loaded into the nasal cone assembly, which can then be transferred from the main assembly of the cutting device back to the delivery device for deployment in a patient. The construction of the nasal cone assembly can vary, including any of the transferable cartridges described herein. In one embodiment, the nasal cone assembly can be mounted relative to the cutting assembly by attaching the proximal end of the nasal cone to the base, such that the longitudinal axis of the lumen of the shaft extending distally from the nasal cone is aligned with the longitudinal axis of the corresponding catheter exiting the slot. The tissue piece can be placed within the loading area of ​​the base relative to a movable stop plate on the main assembly. Both the loading area and the movable stop plate can be part of the base of the main assembly. The piece can be placed inside one or more alignment features of the loading area and slid forward into the cutting area until the piece abuts the stop plate. Once positioned against the stop plate, the tissue piece is positioned by the cutter at a specified width. Therefore, the stop plate provides a calibrated stop point for the tissue piece before cutting. Elements designed to hold the tissue piece in this position can be activated, for example, lowered over the tissue piece to hold the tissue in place, and optionally compressed to a specific height before cutting. Once the retainer plate is lowered over the piece to hold it in place, the cutting rod can be lowered to cut the tissue piece with one or more blades. The stop plate and retainer plate can be removed from the cutting holder, and the remainder of the tissue piece is removed from the assembly. The cutting holder can be loaded using a tissue loader slider. The tissue loader slider pushes the cutting holder into position relative to the longitudinal axis of the shaft in the nasal cone assembly. For example, the tissue loader slider can be positioned and slid forward as far as possible until the slider abuts against a boss on the main assembly, indicating that the cutting holder has been fully delivered into the compression channel and is ready to be advanced into the shaft of the nasal cone assembly. An elongated tool, such as a tissue pusher rod, can be inserted along the longitudinal axis into the main assembly to push the cutting holder from the main assembly into the shaft of the nasal cone assembly. The lever can be designed to push the tissue slider toward the end of the nasal cone assembly without completely pushing the cutting stent out of the shaft's lumen. The nasal cone assembly can then be detached from the main assembly and attached to a delivery device for deployment into the patient.

[0152] In other embodiments, the box 200 itself holds the tissue pieces for cutting. For example, Figure 3AThe lid 214 of the box 200 can be removed from the slot 214 in the base 224, thereby exposing the recess 221. A piece of material 101 can be manually loaded into the recess 221. The piece of material 101 can be sized to receive within the recess 221, or it can be trimmed to ensure its size is suitable for reception within the recess 221. The lid 214 of the box 200 is repositioned onto the base 224 and advanced through the slot 215 until the lower portion 222 of the lid 214 engages with the piece of material 101, trapping it against the protrusion 271. When in the closed configuration, the lid 214 can compress and / or tension the piece of material 101 within the box 200. Figure 2 The loaded tissue box 200 is shown to be installed into the housing 306 of the cutting device 300, with the handle 343 in the open configuration. Once installed, the cutting member 312 can be actuated by lowering the handle 343 toward the base 302, thereby pushing the blade 344 toward the piece of material 101 until the blade 344 of the cutting member 312 completely cuts through the piece of material 101. Figure 4B While the blade 344 is still in the fully cutting position relative to the housing 200, the pusher 320 of the cutting device 300 can be pushed distally to prepare the shaft 210 and position the now-cut support 105 within the cavity 238 of the shaft 210 toward the opening 230 near the distal region 212 of the shaft 210. The pusher 320 can then be retracted from the housing 200, and the housing 200 can be removed from the cutting device 300. As described elsewhere herein, removing the housing 200 from the cutting device 300 may include removing the entire housing 200 from the device 300 or disassembling the nose cone assembly 274 of the housing 200, such as Figure 6 As shown in the image.

[0153] A prepared tissue cassette 200, having a cutting support 105 positioned within the cavity 238 of shaft 210, can be mounted together with the delivery device 400 (e.g., inserted into a reservoir 412 or attached via a bayonet connector 413 or other attachment mechanism 425). The clamping tool 420 of the delivery device 400 is retracted to its proximal position, and the cassette 200 is coupled to the delivery device 400. The clamping tool 420 can be advanced from a first retracted position using a first actuator 415, which is adapted to load the cassette 200 into a second ready position, such that the delivery device 400 and the cassette 200 are now ready for use on a patient.

[0154] Generally, the stent 105 positioned within axis 210 can be implanted through a clear corneal or scleral incision formed using axis 210 or a device separate from cartridge 200. An observation lens, such as a goniomyoscope, can be positioned near the cornea. The observation lens allows visualization of internal areas of the eye, such as the scleral spur and limbus, from a position anterior to the eye. The observation lens may optionally include one or more guide channels sized to receive axis 210. An endoscope can also be used to aid visualization during delivery. High-resolution biological microscopes, OCT, etc., can also be used with ultrasound guidance. Alternatively, a small endoscope can be inserted through another limbal incision in the eye to image the eye during implantation.

[0155] The distal end 216 of shaft 210 can penetrate the cornea (or sclera) to enter the anterior chamber. In this respect, a single incision can be created in the eye, for example, within the limbus. In one embodiment, the incision is very close to the limbus, for example, at the level of the limbus or within 2 mm of the limbus in a clear cornea. Shaft 210 can be used to create the incision or a separate cutting device can be used. For example, a blade-tip device or a diamond blade can be used initially to enter the cornea. A second device with a scraper tip can then be advanced above the blade tip, wherein the plane of the scraper is positioned to coincide with the anatomical plane. The scraper tip device can be shaft 210.

[0156] The corneal incision can be of a size sufficient to allow axis 210 to pass through. In one embodiment, the incision size is approximately 1 mm. In another embodiment, the incision size is no greater than approximately 2.85 mm. In yet another embodiment, the incision is no greater than approximately 2.85 mm and greater than approximately 1.5 mm. It has been observed that the incision up to 2.85 mm is a self-sealing incision.

[0157] After insertion through the incision, the shaft 210 can be advanced into the anterior chamber along a pathway that allows the support 105 to be transported from the anterior chamber to a target location (e.g., the supraciliary space or the suprachoroidal space). By positioning the shaft for access, the shaft 210 can be further advanced into the eye such that the distal end 216 of the shaft 210 penetrates tissue at the corner of the eye, such as the iris root or ciliary body region, or the portion of the iris root of the ciliary body near its tissue boundary with the scleral process.

[0158] The scleral spur is an anatomical landmark on the canthal wall of the eye. It is above the level of the iris but below the level of the trabecular meshwork. In some eyes, the scleral spur may be obscured by the lower band of the pigmented trabecular meshwork and located directly behind it. Axis 210 can travel along a pathway toward the canthus and the scleral spur, such that it passes near the scleral spur on its way to the supraciliary space of the ciliary body, but does not need to penetrate the scleral spur during delivery. Instead, axis 210 can be adjacent to the scleral spur and move downwards to dissect the tissue boundary between the sclera and the ciliary body, with the anatomical entry point beginning directly below the scleral spur, near the root of the iris, or near the iris root portion of the ciliary body. In another embodiment, the delivery pathway of the implant intersects with the scleral spur.

[0159] Axis 210 can approach the corner of the eye from the same side of the anterior chamber as the deployment location, so that axis 210 does not have to advance through the iris. Alternatively, axis 210 can approach the corner of the eye from through the anterior chamber AC, so that axis 210 advances across the iris and / or anterior chamber toward the opposite corner of the eye. Axis 210 can approach the corner of the eye along multiple pathways. Axis 210 does not necessarily traverse the eye and does not intersect the central axis of the eye. In other words, when viewed along the optical axis, the corneal incision and the implantation location of stent 105 at the corner of the eye can be in the same quadrant. Furthermore, the pathway of stent 105 from the corneal incision to the corner of the eye should not cross the central line of the eye to avoid touching the pupil.

[0160] The axis 210 can be continuously advanced into the eye, for example, about 6 mm. The anatomical plane of the axis 210 can follow the curve of the inner scleral wall, such that the support 105 mounted in the axis, for example after penetrating the iris root or the iris root portion of the ciliary body CB, 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 support 105 extends through the supraciliary space of the ciliary body and then further lies between the tissue boundary of the sclera and the choroid that forms the suprachoroidal space.

[0161] Once correctly positioned, the bracket 105 can be released from the shaft 210. In some embodiments, the bracket 105 can be released by retracting the shaft 210 while the clamping tool 420 prevents the bracket 105 from retracting along with the shaft 210.

[0162] Once implanted, the stent 105 establishes a fluid communication pathway between the anterior chamber and the target access (e.g., the supraciliary space or the suprachoroidal space). As described above, the stent 105 is not limited to implantation in the suprachoroidal space or the supraciliary space. The stent 105 can be implanted at other locations within the anterior chamber and the eye to provide fluid communication, such as Schrem's canals or subconjunctival locations of the eye. In another embodiment, the stent 105 is implanted to establish a fluid communication pathway between the anterior chamber and Schrem's canals and / or between the anterior chamber and a subconjunctival location of the eye. It should be understood that the device described herein can also be used for stent delivery via the scleral route and from the internal pathway.

[0163] As mentioned above, the material used to form the scaffold can be impregnated with one or more therapeutic agents for additional treatment of the course of eye disease.

[0164] The stents described in this article can be used to prevent or treat a variety of systemic and eye diseases, such as inflammation, infection, and cancerous growths. More specifically, they can treat or prevent eye diseases such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, herpes simplex virus, and adenovirus infections.

[0165] The following classes of drugs can be delivered using the device of the present invention: antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport / fluidity approximators (e.g., colchicine, vincristine, cytochalasin B, and related compounds); antiglaucoma drugs, including β-blockers such as timolol, betalol, atenolol, and prostaglandin analogs such as bimatoprost, travoprost, latanoprost, etc.; carbonic anhydrase inhibitors, such as acetazolamide, metronidazole, dichlorobenazine, sulfadiazine; and neuroprotective agents such as nimodipine and related compounds. Other examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, brevicin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; antibacterial agents such as sulfonamides, sulfaacetamide, sulfadimazole, and sulfisoxazole; antifungal agents such as fluconazole, furacilin, amphotericin B, ketoconazole, and related compounds; antiviral agents such as trifluorothymidine, acyclovir, ganciclovir, DDI, AZT, foscamet, vidarabine, trifluorouridine, herpes simplex virus, ribavirin, protease inhibitors, and anticytomegalovirus agents; and antihistamines such as dexamethasone; chlorpheniramine maleate. Phosphoric acid, piracetam, and pyridine; anti-inflammatory drugs, such as hydrocortisone, dexamethasone, fluocinolone acetonide, prednisone, prednisolone, methylprednisolone, flumethasone, betamethasone, and triamcinolone; decongestants, such as phenylephrine, naphazoline, and tetrahydrazine; miotics and anticholinesterases, such as pilocarpine, carbachol, diisopropyl fluorophosphate, iodophosphine, and diergotamine bromide; mydriatics, such as atropine sulfate, cyclopentolpine, homatropine, scopolamine, tocatropine, and eucatropine; sympathomimetic drugs, such as adrenaline, vasoconstrictors, and vasodilators; ranibizumab, bevacizumab, and triamcinolone.

[0166] Nonsteroidal anti-inflammatory drugs (NSAIDs) may also be delivered, such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, such as ASPIRIN® from Bayer AG, Leverkusen, Germany; ibuprofen, such as ADVIL® from Wyeth, Collegeville, Pennsylvania; indomethacin; mefenamic acid), COX-2 inhibitors (CELEBREX® from Pharmacia, Peapack, New Jersey; COX-1 inhibitors), including the prodrug Nepafenac®; immunosuppressants, such as Sirolimus (RAPAMUNE® from Wyeth, Collegeville, Pennsylvania), or matrix metalloproteinase (MMP) inhibitors that act early in the inflammatory response pathway (e.g., tetracycline and tetracycline derivatives). Anticoagulants may also be delivered, such as heparin, antifibrinogen, fibrinolytic agents, anticoagulant activating enzymes, etc.

[0167] Antidiabetic agents that can be delivered using this device include acetylhexylamine, chlorsulfonylurea, glipizide, glibenclamide, toprazole, tolbutamide, insulin, aldose reductase inhibitors, etc. Some examples of anticancer agents include 5-fluorouracil, doxorubicin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, daunorubicin, doxorubicin, estradiol, etoposide, ivermectin, filgrastim, fluorouracil, fludarabine, fluorouracil, fluorometholone, flutamide, goserelin, isosylurea, leuprorelin, levamisole, lomustine, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, pentostatin, piperobroman, procamycin, procarbazine, saxagmustine, streptozotocin, tamoxifen, paclitaxel, teniposide, thioguanine, uracil mustard, vincristine, vinblastine, and vindesine.

[0168] This device can be used to deliver hormones, peptides, nucleic acids, carbohydrates, lipids, glycolipids, glycoproteins, and other macromolecules. Examples include: endocrine hormones such as pituitary hormones, insulin, insulin-associated growth factor, thyroid hormone, and growth hormone; heat shock proteins; immunomodulators such as muramyl dipeptide, cyclosporine, interferons (including α, β, and γ interferons), interleukin-2, cytokines, FK506 (an epi-pyrido-oxazolidinyl tricocinone, also known as tacrolimus), tumor necrosis factor, pentostatin, thymopentin, transforming factor beta2, and erythropoietin; antitumor proteins (e.g., anti-vascular endothelial growth factor, interferon), and anticoagulants, including anticoagulant activating enzymes. Other examples of macromolecules that can be delivered include monoclonal antibodies, brain nerve growth factor (BNGF), brain nerve growth factor (CNGF), vascular endothelial growth factor (VEGF), and monoclonal antibodies against these growth factors. Other examples of immunomodulators include tumor necrosis factor inhibitors, such as thalidomide.

[0169] In various embodiments, reference is made to the accompanying drawings. However, some embodiments may be implemented without one or more of these specific details, or in combination with other known methods and constructions. Numerous specific details, such as specific constructions, dimensions, and processes, are set forth in the description to provide a thorough understanding of the embodiments. In other instances, well-known processes and manufacturing techniques have not been described in particular detail so as not to unnecessarily obscure the description. References to “an embodiment,” “an example,” “a particular implementation,” “implementation,” etc., throughout this specification mean that the particular feature, structure, construction, or characteristic described is included in at least one embodiment or implementation. Therefore, the phrases “an embodiment,” “an example,” “a particular implementation,” “implementation,” etc., appearing throughout different places in this specification do not necessarily refer to the same embodiment or implementation. Furthermore, particular features, structures, constructions, or characteristics may be combined in any suitable manner in one or more embodiments.

[0170] The use of relative terms throughout the description can indicate relative positions or directions. For example, "distal" can indicate a first direction away from a reference point. Similarly, "proximal" can indicate a position in a second direction opposite to the first direction. The reference point used herein can be the operator, such that the terms "proximal" and "distal" refer to the operator using the device. The device region closer to the operator can be described herein as "proximal," while the device region farther from the operator can be described herein as "distal." Similarly, the terms "proximal" and "distal" can also be used herein to refer to the patient's anatomical position from the operator's perspective or from the point of entry or along the insertion path from the system's point of entry. Thus, a proximal position might refer to a position within the patient's body closer to the device's point of entry along the insertion path toward the target, while a distal position might refer to a position within the patient's body farther from the device's point of entry along the insertion path toward the target location. However, these terms are provided to establish a relative frame of reference and are not intended to limit the use or orientation of the device to the specific configurations described in the various embodiments.

[0171] As used herein, the term "about" refers to a range of values ​​that includes a specified value and that would be reasonably thought by one of ordinary skill in the art to be reasonably similar to the specified value. In some aspects, "about" means using measurements generally acceptable in the art within a standard deviation. In some aspects, "about" means a range extending to + / - 10% of the specified value. In some aspects, "about" includes the specified value.

[0172] Although this specification contains numerous details, these should not be construed as limiting the scope of the claimed or potentially claimed content, but rather as descriptions of specific features of particular embodiments. Certain features described in the context of individual embodiments in this specification may also be implemented in combination in a single embodiment. Rather, the various features described in the context of a single embodiment may also be implemented individually or in any suitable sub-combination in multiple embodiments. Furthermore, although features may be described above as functioning in certain combinations and even initially claimed in this way, in some cases one or more features from a claimed combination may be removed from that combination, and the claimed combination may be for sub-combinations or variations thereof. Similarly, although operations are depicted in a specific order in the drawings, this should not be construed as requiring these operations to be performed in the specific order shown or sequentially, or requiring all illustrated operations to be performed to obtain the desired result. Only a few examples and implementations are disclosed. Variations, modifications, and enhancements may be made to the described examples and implementations, as well as other implementations, based on the disclosure.

[0173] In the foregoing description and claims, phrases such as “at least one of…” or “one or more of…” may appear after a linked list of elements or features. The term “and / or” may also appear in a list of two or more elements or features. Unless there is an implied or explicit contradiction with the context in which it is used, such phrases are intended to mean any element or feature listed individually or any referenced element or feature combined with any other referenced element or feature. 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 “A alone, B alone, or A and B together.” Similar interpretations are also 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” each mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.”

[0174] The use of the term "based on" in the foregoing and claims is intended to mean "at least partially based on," thus allowing for features or elements not listed.

[0175] The systems disclosed herein can be packaged together in a single package. The finished product packaging will be sterilized using a sterilization method such as ethylene oxide or radiation, labeled, and boxed. Instructions for use may also be provided inside the packaging or via an internet link printed on the label.

Claims

1. A system for preparing an implant and inserting the implant into a patient's eye, the system comprising: Tissue box, the tissue box comprising: Nasal cone, the nasal cone including a proximal connector on a distal region and a proximal region; and A distal axis extending from the distal region of the nasal cone, the distal axis defining a lumen from the proximal region to the distal region of the distal axis, wherein at least the distal region of the distal axis is sized and shaped for insertion into the anterior chamber of the eye; and A delivery device comprising a proximal handle having a distal region defining a distal connector, the distal connector being sized to engage and reversibly connect with the tissue cassette via a proximal connector on the proximal region of the nasal cone.

2. The system according to claim 1, wherein, The proximal connector and the distal connector include a male-to-female connection for reversible coupling between the proximal region of the nasal cone and the distal region of the proximal handle.

3. The system according to claim 1 further includes a cutting device, wherein, The cutting device includes a cutting component configured to cut pieces of bio-derived material into implants.

4. The system according to claim 1, wherein, The delivery device further includes at least one actuator configured to deploy an implant positioned within the lumen of the distal axis from a distal opening and into the eye.

5. The system according to claim 4, 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 cavity after the implant is positioned within the cavity.

6. The system according to claim 5, wherein, The at least one actuator is configured to retract the nasal cone relative to the tool to deploy the implant from the distal opening.

7. The system according to claim 5, wherein, The at least one actuator is configured to advance the tool relative to the nasal cone to deploy the implant from the distal opening.

8. The system according to claim 1, wherein, The distal axis of the tissue box is configured to deliver viscous material.

9. The system according to claim 3, wherein, The cutting component includes at least a first blade.

10. The system according to claim 9, wherein, The cutting component includes a second blade spaced apart from the first blade by a distance.

11. The system according to claim 10, wherein, Actuation of the cutting member pushes the first and second blades toward the bio-derived material sheet and cuts through the bio-derived material sheet by a thickness, thereby forming the implant, wherein the distance is equal to the width of the implant.

12. The system according to claim 3, wherein, The cutting device also includes a handle movably coupled to the base, the handle being configured to actuate the cutting member.

13. The system according to claim 3, wherein, The bio-derived material is a harvested or engineered tissue, organ, or part of an organ.

14. The system according to claim 3, wherein, The bio-derived material is an autologous graft, allogeneic graft, or xenograft material.

15. The system according to claim 3, wherein, The bio-derived material is substantially absorbed after the implant is positioned inside the eye, and wherein, once absorbed, space is retained at the location where the implant was previously positioned.

16. The system according to claim 1, wherein, The distal axis is sized to be inserted through a corneal incision no larger than 2.85 mm.

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