CN118055742A - System for shaping and implanting a biological intraocular stent for increasing water outflow and reducing intraocular pressure - Google Patents

Abstract

A system for deploying an implant excised from biological tissue into an eye of a patient includes a delivery device and a nose cone assembly, a tubular shaft protruding from a distal region of the nose cone and including an inner lumen. Related devices, systems, and methods are provided.

Description

System for forming and implanting a biological intraocular scaffold for increasing aqueous outflow and reducing intraocular pressure

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. §119(e) to co-pending provisional patent applications Serial No. 63/241,713, filed on September 8, 2021, Serial No. 63/252,753, filed on October 6, 2021, and Serial No. 63/271,639, filed on October 25, 2021. The disclosures of these provisional applications are incorporated herein by reference in their entireties.

This application is also a continuation-in-part of U.S. Application Serial No. 17/325,785, filed on May 20, 2021, which claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Applications Serial No. 63/027,689, filed on May 20, 2020, and Serial No. 63/163,623, filed on March 19, 2021. The disclosures of these applications are incorporated herein by reference in their entireties.

Background technique

The mainstay of ophthalmic surgery for glaucoma is to increase aqueous outflow from the eye. There are several approaches to this surgery, including: 1) external trabeculectomy or shunting, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a transscleral outflow pathway; 2) internal trabecular or transscleral outflow stenting or aqueous shunts using hardware-based implantable devices or using ablative, non-implantable cutters such as dual blades and trabeculectomy devices; and 3) internal epi-parietal stenting using implantable non-biologic hardware implants.

Current endoscopic stenting devices and methods are based on non-biological hardware materials such as polyimide, polyethersulfone, titanium, polystyrene block-isobutylene block-styrene, etc. Such implantable devices based on non-biological hardware have significant drawbacks as they can cause severe erosion, fibrosis, and ocular tissue damage, such as endothelial cell loss.

In view of the foregoing, there is a need for improved devices and methods related to ophthalmic surgery for treating glaucoma.

Summary of the invention

In one aspect, a system for deploying an implant cut from biological tissue into an eye of a patient is described, the system comprising a delivery device having a proximal housing; at least one actuator; and a distal coupler. The system comprises a nose cone assembly having a nose cone having a proximal region and a distal region; a coupler on the proximal region of the nose cone configured to reversibly engage with a distal coupler of the delivery device; and a tubular shaft protruding from the distal region of the nose cone and having an inner lumen. The tubular shaft has one or more fenestrations extending through a sidewall of the shaft, the one or more fenestrations being covered by a translucent or transparent material so as to reveal the inner lumen of the tubular shaft.

In a related aspect, a device for minimally modifying biologically derived tissue is described, the device comprising two blades separated by a gap, each blade having an inner face and at least one distal bevel forming a cutting edge. The two blades are mounted at an angle relative to each other such that the inner faces are non-parallel and the distal bevels are parallel to each other. The device is configured to cut the biologically derived tissue into an elongated strip having a length and a width, wherein the length is greater than the width.

In a related aspect, a cartridge for use with a system for preparing an implant and inserting the implant intraocularly into an eye is described. The cartridge includes a lower member having a planar upper surface sized and shaped to receive a piece of material to be cut into an implant; an upper member movably coupled to the lower member between an open configuration and a closed configuration, the upper member having a lower surface arranged to oppose the upper surface of the lower member when the upper member is in the closed configuration; and a pair of blades configured to extend below the lower surface of the upper member to cut the piece of material into the implant.

In a related aspect, a system for preparing an implant for implantation in an eye of a patient and inserting the implant into the eye of the patient is described. The system includes a box configured to hold a sheet of material and having a pair of blades configured to cut the sheet to form an implant from the sheet; and a delivery instrument having a housing and a distal portion sized and shaped for insertion into the anterior chamber of the eye. The distal portion has an inner cavity having an elongated tubular member sized to receive the implant cut from the sheet with the pair of blades.

In a related aspect, a system for preparing an implant for implantation in an eye of a patient and inserting the implant into the eye of a patient is described. The system includes a cartridge configured to contain and retain a material within the cartridge; at least one cutting member configured to cut the material to form an implant from the material; and a delivery instrument having a housing and a distal portion sized and shaped for insertion into the anterior chamber of the eye, wherein the distal portion includes a lumen having an elongated tubular member.

In a related aspect, a system for preparing an implant and inserting the implant intraocularly into an eye is described. The system includes a blade box configured to move between an open configuration and a closed configuration for loading a piece of material into the box. The box includes a lower component having an upper surface configured to receive a piece of material; an upper component having a lower surface configured to abut against the piece of material when the box is in a closed configuration; and a pair of blades and a spacer defining a gap between the blades. The pair of blades are configured to extend below the lower surface of the upper component to penetrate the piece of material at two locations, thereby forming a strip of material having a width narrower than the width of the piece of material when the blade box is moved into the closed configuration.

In a related aspect, a system for deploying an implant cut from biological tissue into an eye of a patient is described. The system includes a delivery device having a proximal housing; at least one actuator coupled to a push rod; and a distal coupler. The system includes a nose cone assembly having a nose cone having a proximal region and a distal region; a coupler on the proximal region of the nose cone configured to reversibly engage with a distal coupler of the delivery device; and a tubular shaft protruding from the distal region of the nose cone and including an inner cavity, the tubular shaft including a distal region and a proximal region. The distal region is curved away from a longitudinal axis of the proximal region.

In some variations, one or more of the following may be optionally included in any feasible combination of the above methods, devices, apparatuses, and systems. More details are set forth in the accompanying drawings and the following description. Other features and advantages will become apparent from the specification and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects will now be described in detail with reference to the following drawings. In general, the drawings are not absolute or relative to scale, but are intended to be illustrative. In addition, the relative placement of features and elements may be modified for clarity of illustration.

1A-1B are cross-sectional views of a human eye showing the anterior chamber and vitreous chamber of the eye with a stent in example locations in the eye;

FIG2 is a perspective view of a system according to one embodiment;

3A and 3B illustrate an embodiment of the tissue cassette of the system of FIG. 2 with the cover removed;

FIG3C shows the tissue cassette of FIGS. 3A-3B with the cover installed;

FIG4A shows the cutting device of the system of FIG2 with a tissue cassette installed and the cutter in an open configuration;

FIG4B shows the cutting device of FIG4A with the tissue cassette installed and the cutter in the cutting configuration;

FIG4C is a partial view of the cutting device of FIG4B showing the cutter;

FIG4D is a partial cross-sectional view of the cutting device of FIG4A;

FIG4E is a partial cross-sectional view of the cutting device of FIG4B ;

4F-4G illustrate the pusher of the cutting device of FIG. 4A in advanced and withdrawn configurations, respectively, relative to the base of the cutting device;

FIG4H is a cross-sectional view of the cutting device of FIG4G ;

4I-4J are partial cross-sectional views of the cutting device of FIG. 4F ;

FIG5A shows the transport device of the system of FIG2 with the tissue cassette installed and the pusher in an advanced configuration;

Fig. 5B shows the transport device of Fig. 5A with the cartridge retracted relative to the pusher;

FIG5C illustrates the distal region of the tissue cassette and delivery device of FIG5A ;

FIG5D shows a tissue cassette installed in the transport device of FIG5C;

FIG5E shows the pusher of the delivery device of FIG5A advanced to a deployed position;

FIG5F shows the tissue cassette being retracted by the delivery device to deploy the cut stent within the eye;

FIG6 is a perspective view of a system according to a related embodiment;

7A and 7B illustrate the tissue cassette of FIG. 6 with the cover in a loading configuration;

FIG7C shows the tissue cassette of FIGS. 7A-7B with the cover installed;

FIG8 shows the cutting device and tissue cassette of FIG6 ;

FIG. 9A illustrates an embodiment of a cutting device with a tissue cassette installed, the cutter in a cutting configuration, and the nose cone of the tissue cassette detached;

FIG. 9B illustrates an embodiment of a delivery device with the nose cone of the tissue cassette engaged and the pusher in a retracted configuration;

FIG9C shows the delivery device of FIG9B with the pusher advanced to a ready configuration;

FIG9D illustrates the delivery device of FIG9C with the nose cone retracted relative to the pusher;

FIG10A shows the nose cone prior to engagement with the distal region of the delivery device;

FIG10B shows the nose cone after engagement with the distal region of the delivery device and prior to attachment;

FIG10C shows the nose cone engaged and attached to the distal region of the delivery device;

FIG. 11A shows the pusher of the delivery device of FIG. 10A in a first retracted position;

FIG. 11B shows the pusher of the conveyor of FIG. 10A advanced to a second ready position;

FIG11C shows the distal shaft of the delivery device of FIG10A within an eye and the third actuator ready to be activated;

12A-12B are cross-sectional views of the delivery device of FIG. 10A showing a first retracted position of FIG. 11A ;

12C-12D are cross-sectional views of the conveyor of FIG. 10A showing a second ready position of FIG. 11B ;

13A-13B illustrate a reset mechanism of the delivery device of FIG. 10A ;

14A-14H illustrate stages of use of different embodiments of a cutting assembly for cutting a stent and transferring the stent to a portion of a tissue cassette;

FIG14I schematically illustrates an embodiment of a nose cone assembly coupled to a cutting assembly;

15A-15B illustrate another embodiment of a cutting device for cutting a stent;

FIG16A is a side view of an embodiment of a nose cone assembly;

FIG16B is a distal end view of the distal tip taken along arrows B-B in FIG16A;

FIG16C is a detailed view of the distal end region of the distal shaft of FIG16A taken at circle A;

FIG. 17A illustrates the proximal housing of the delivery device of FIG. 10A having a keyed coupling for receiving a nose cone assembly;

17B-17C show the nose cone assembly of FIG. 16A for coupling with the proximal housing of FIG. 17A from a front end view and a rear end view, respectively;

FIG17D shows the nose cone assembly coupled to the proximal housing;

FIG17E illustrates a detailed view of the distal shaft of the nose cone assembly of FIG16A with the pusher visible within the bevel;

FIG17F shows a detailed exploded view of the distal shaft and push rod;

17G-17H are partial transparent views of the actuator in a ready position;

FIG17I is a perspective view of an actuator having a flexure;

FIG. 18A shows an embodiment of a cutting device;

FIG. 18B illustrates the cutting device of FIG. 18A with the handle articulated in an open configuration;

FIG. 18C shows the cutting device of FIG. 18B with the pressure pad in an open configuration, thereby exposing the load-bearing surface;

FIG18D is a detailed view of the cutting device of FIG18C;

FIG18E is a schematic diagram of a cutting assembly of the cutting device of FIG18A;

FIG18F is a perspective view of the cutting device associated with FIG18A;

FIG18G is a cross-sectional view of the device of FIG18F taken along line G-G;

Fig. 18H is a detailed view of the dual blades of the device of Fig. 18F;

FIG19A is an embodiment of a loading device prior to coupling the nose cone assembly to the receptacle;

FIG19B is an embodiment of the loading device after coupling the nose cone assembly to the receptacle;

20A-20B are schematic cross-sectional views of a loading device for aligning and compressing a cut stent prior to loading the cut stent into a delivery shaft;

FIG21A is a perspective view of an embodiment of a trephine device engaged with a blade cartridge;

FIG21B is a perspective view of the trephine device of FIG21A with the blade cartridge uncoupled;

Fig. 22A is an end view of the trephine device of Fig. 21A showing the blade of the blade cartridge relative to the bearing surface;

FIG22B is a detailed view of the blade of the trephine device of FIG21A;

FIG22C is a detailed view of the cutting edge of the blade of FIG22B taken at circle C;

FIG22D shows a single bevel blade;

FIG22E shows a double bevel blade;

23A-23C are perspective and end views of an ejector spring between blades of the blade cartridge of the trephine device of FIG. 21A.

It should be understood that the drawings are merely schematic and are not intended to be drawn to scale. It should be understood that the devices described herein may include features that are not necessarily depicted in every drawing.

Detailed ways

Implants, systems and methods for increasing aqueous outflow from the anterior chamber of the eye are disclosed. As will be described in detail below, intra-path outflow stenting using biological, cell-based or tissue-based materials provides biocompatible aqueous outflow enhancement with improved tolerability and safety compared to conventional shunts. In an exemplary embodiment, a cutting device, also referred to herein as a trephine device or cutting tool, is used to collect or generate biological tissue or biologically derived materials in vitro and form an implant, also referred to herein as a stent. In one embodiment, the stent is an elongated body or material having an inner cavity to provide a passage for drainage. In a preferred embodiment, the stent is an elongated body or tissue strip that has no inner cavity and is configured to maintain a cleft and provide a ciliary stent (or in another anatomical location such as Schlemm's canal or transscleral stenting). Lumen-based devices may be limited by the lumen as a fibrotic occluded passage. The stent formed from the tissue is then implanted into the eye through an intra-path delivery pathway to provide aqueous outflow from the anterior chamber. The stent described herein can be used as a minimally invasive glaucoma surgery (MIGS) treatment and as an adjunct or stand-alone treatment for phacoemulsification of glaucoma.

The use of terms such as stent, implant, shunt, biological tissue, or tissue is not intended to limit any one structure or material. The implanted structure can, but need not, be of a material that is substantially absorbed into the ocular tissue after placement in the eye, such that once absorbed, a space may remain where the structure was previously located. Once implanted, the structure may also remain in place for an extended period of time and not substantially corrode or absorb.

As will be described in more detail below, the stents described herein can be made of biologically derived materials that do not cause toxic or harmful effects after implantation in a patient.

The term "biologically derived materials" includes naturally occurring biological materials and synthetic biological materials suitable for implantation in the eye and combinations thereof. Biologically derived materials include materials that are natural biological structures, which have biological arrangements that occur naturally in mammalian subjects, including organs or organ parts formed by tissues, and tissues formed by materials combined together according to structure and function. Biologically derived materials include tissues, such as cornea, sclera, or cartilage tissue. Tissues considered herein may include any of the following multiple tissues, including muscle, epithelium, connective tissue, and neural tissue. Biologically derived materials include tissues, organs, organ parts, and tissues from subjects collected from donors or patients, including a piece of tissue suitable for transplantation, including autologous grafts, allografts, and xenograft materials. Biologically derived materials include naturally occurring biological materials, including any material that occurs naturally in mammals. As used herein, biologically derived materials also include materials that are engineered to have biological arrangements similar to natural biological structures. For example, the material can be synthesized using in vitro techniques, such as by inoculating a three-dimensional skeleton or matrix with appropriate cells, engineered or 3D-printed materials to form a biological structure suitable for implantation. As used herein, biologically derived materials also include cell-derived materials, including stem cell-derived materials. In some embodiments, the biologically derived material comprises an injectable hyaluronate hydrogel or viscous material, such as GEL-ONE cross-linked hyaluronate (Zimmer).

Biologically derived materials may include naturally occurring biological tissue, including any material naturally occurring in mammals, that has been minimally manipulated or more than minimally manipulated in accordance with FDA guidance under 21 CFR 1271.3(f) such that processing the biological tissue does not alter the relevant biological properties of the tissue (see Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use, www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal).

In some embodiments, the bioscaffold 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 combine multiple openings throughout. For example, the wall of the printed material can be designed to have multiple openings so that the liquid in the inner cavity can seep out or flow outward through the tube wall, so that the tube has sufficient porosity to ensure that water is discharged from the eye. The tube can be printed to have a size modified at or near the time of delivery. For example, the 3D printed material can be designed to have a first size that is convenient for manual operation. At or near the time of delivery, the 3D printed material can be cut into a size more suitable for implantation into the eye. In the case where the piece of material is described as being cut or trephinated into a stent before implantation, it should be understood that the piece of material can be a printed material with a specific 3-dimensional shape (e.g., including a tubular shape) and is cut into a stent by cutting into a shorter desired length. Therefore, in some embodiments, the stent described herein does not have to be solid and can also be combined with a lumen.

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 hard biological tissue. The biological tissue can be hydrophilic or hydrophobic. The biological tissue can include or be impregnated with one or more therapeutic agents for additional treatment of an ocular disease process.

The bioscaffold material may be used in combination with one or more therapeutic agents so that it can be used to additionally deliver the agent to the eye. In one embodiment, the biological tissue may be embedded with a slow-release pellet, or soaked in a therapeutic agent for slow-release delivery to the target tissue.

Non-biological materials include synthetic materials prepared by artificial synthesis, processing or manufacturing, which may be biocompatible but are not cell-based or tissue-based. For example, non-biological materials include polymers, copolymers, polymer blends and plastics. Non-biological materials include inorganic polymers such as silicone rubber, polysiloxane, polysilane; and organic polymers such as polyethylene, polypropylene, polyethylene compounds, polyimide, etc.

Regardless of the source or type of the biologically derived material, the material can be cut or trephinated into an elongated shape suitable for stenting and implantation in the eye. The cutting process of the tissue can be performed prior to or during the surgical implantation process. The stent (one or more) implanted in the eye can have a structure and/or permeability that allows water to flow out of the anterior chamber when positioned within the cyclodialysis cleft.

Bioderived materials can be minimally modified or minimally manipulated tissues for eyes. Minimally modified bioderived materials do not involve the combination of the material with another product, except for example water, sterilants, preservatives, low-temperature preservatives, storage agents and/or drugs or therapeutic agents (one or more) and the like. Minimally modified bioderived materials will not produce systemic effects once implanted, and their main functions do not rely on the metabolic activity of any living cells. During each step of the preparation and use method, the bioderived material can be minimally manipulated to maintain the original relevant characteristics of the biological tissue. The cut stent can be a structural tissue that physically supports or serves as a barrier or conduit, for example, by at least partially maintaining the ciliary cleft formed in the eye. Cutting stents from bioderived materials can be minimally manipulated by compression, compaction, folding, rolling or other types of temporary operations on the cut stent, and once released from the force of applying compression or compaction, the cut stent allows the material to recover to its original structure. Thus, minimal manipulation can temporarily mechanically change the size or shape of the cut tissue while still maintaining the original relevant features of the tissue once the mechanical change is eliminated, which relate to its utility for reconstruction, repair or replacement. For example, the bioderived material can be sclera, which is cut into a shape that is oversized relative to the inner diameter of the delivery tube through which the stent is implanted. Minimal manipulation of the cut stent can include temporarily compressing the sclera material into the lumen of the delivery shaft so that after implantation in the eye, the cut stent tends to recover toward its original cut size. Although the bioderived materials described herein are described in the context of being cut into a stent-like implant, which can maintain a rift for water outflow, other methods are contemplated herein. For example, the bioderived material can be compressed into a plug, which is then implanted into a region of the eye for other purposes, such as stenting, occlusion of traumatic ruptures, over-filtered bubbles, posterior wall ruptures, and other indications.

Minimal structural modification of biological tissue (e.g., scleral tissue or corneal tissue) or other biological tissue (cross-linked or uncross-linked) for implantable intraocular use can include longitudinal trephination into elongated tissue strips having a width less than its length, for example, before loading in the delivery shaft, the length can be greater than 2mm and less than 30mm, and the thickness can be between about 0.1mm and 2.0mm, and the width can be between about 0.1mm and 2.0mm. As will be described in more detail herein, the cutting of biological tissue allows the width of the cut to be adjusted and the biological tissue can be compressed to a specific, consistent thickness at the same time. The cut biological tissue can be loaded in a manner that the biological tissue is compressed into a delivery channel to be loaded into a shuttle mechanism (shuttle) of a nose cone assembly or box, for example, as described herein. The loading assembly may include features and linkages that prevent the pusher from buckling when it transfers the biological tissue from the loader to the shuttle mechanism. The cutting, loading and transfer for delivery can be combined in a single assembly, or can be performed by separate assemblies that are constructed to work in conjunction with each other. One or more components of the assembly described herein can be provided as ready-to-use items. For example, biological tissue may be pre-cut and provided within a pre-loaded shuttle assembly, which is sold, for example, as a ready-to-use assembly or partially ready-to-use component coupled to a delivery handpiece.

1A-1B are cross-sectional views of a human eye showing the anterior chamber AC and vitreous chamber VC of the eye. The support 105 can be positioned in the eye at an implantation position so that at least a first portion of the support 105 is positioned in the anterior chamber AC, and a second portion of the support 105 is positioned in the tissue, such as in the supraciliary space and/or suprachoroidal space of the eye. The size and shape of the support 105 are designed so that the support 105 can be positioned in such a configuration. The support 105 provides or otherwise serves as a channel for aqueous humor to flow away from the anterior chamber AC (e.g., to the supraciliary space and/or suprachoroidal space). In FIGS. 1A-1B , the support 105 is schematically represented as an elongated body relative to the delivery shaft 210. It should be understood that the size and shape of the support 105 can vary. In addition, the size and shape of the support 105 before insertion into the delivery shaft 210 can be changed when the delivery shaft 210 is inserted, and can be changed after being deployed from the delivery shaft 210.

Stent 105 can be implanted by inner road (ab interno), for example, through clear corneal incision or scleral incision.Stent can be implanted to produce opening or cleft, to enhance outflow communication between anterior chamber AC and ciliary body supracaval space, anterior chamber AC and suprachoroidal space, anterior chamber AC and Schlemm's (Schlemm) canal or anterior chamber AC and subconjunctival cavity, or any other eye compartment, tissue or interface where occlusion, stent placement and/or tissue enhancement are clinically indicated.In a preferred embodiment, stent 105 is implanted so that the distal end is positioned in the ciliary body supracaval position, and the proximal end is positioned in anterior chamber AC, to provide ciliary body supracaval fissure.The distal end of stent 105 can be positioned between other anatomical parts of the eye.

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

The support 105 described herein can be formed of any of a variety of biologically derived materials having a permeability and/or structure that allows water to filter through it. The support 105 can be formed of biologically derived materials that are collected, engineered, grown, or otherwise manufactured. The biologically derived support material can be obtained or collected from a patient or donor. The biologically derived support material can be collected before or during surgery. The biologically derived support material can be a synthetic biological tissue produced using in vitro technology. The biologically derived material can be stem cell-generated or bioengineered. The tissue can be produced by in situ cell or non-cellular growth. In an exemplary embodiment, the tissue can be 3D printed during manufacturing. The biologically derived material can be a minimally manipulated material that retains its original structural characteristics as a tissue.

The 3D printed tissue can be printed as a larger piece of material that is then cut during surgery, as described elsewhere herein. Alternatively, the 3D printed tissue can be printed to have the size of the final implantable scaffold. In this embodiment, the 3D printed material does not need to be cut before implantation, but can be implanted directly. For example, the 3D printed scaffold can be printed directly into a box that is configured to be operably connected to a delivery device described herein, which in turn is used to deploy the 3D printed scaffold into the eye. The 3D printed scaffold can be generated using the 3D printing process described in Biofabrication, 2019; 11(3).

In an example embodiment, the support 105 is made of biological tissue. The biologically derived material can be corneal tissue and/or non-corneal tissue. The biologically derived material can include cornea, sclera, collagen or cartilage tissue. In one embodiment, the biologically derived support material can be a bare corneal stroma tissue without epithelium and endothelium, which is porous and has hydrophilic permeability to allow water filtration. The biologically derived material can be a minimally manipulated sclera that retains its original structural features as a tissue. The biologically derived material of the support 105 can but need not be incorporated into the inherent anatomical structure of the eye after being placed in the eye. The support can form a passage that remains open for a long time in the surrounding tissue, even after the support is absorbed. The biologically derived support material may not be significantly absorbed or incorporated into the anatomical structure of the eye, so that the support 105 is implanted for a long period of time or indefinitely as needed.

In other embodiments, the scaffold 105 material can be made of complex carbohydrates or non-inflammatory collagen. The scaffold 105 can also be formed of biodegradable or bioabsorbable materials, including biodegradable polymers, including hydroxy aliphatic carboxylic acids, homopolymers or copolymers, such as polylactic acid, polyglycolic acid, polylactic 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 methylcellulose phthalate and calcium alginate), polypropylene, polybutyrate, polycarbonate, acrylate polymers, such as polymethacrylate, polyanhydride, polyvalerate, polycaprolactone such as poly-c-caprolactone, polydimethylsiloxane, polyamide, polyvinyl pyrrolidone, polyvinyl alcohol phthalate, wax (such as paraffin and white beeswax), natural oil, shellac, zein or mixtures. The scaffold 105 can be formed of hyaluronate hydrogel or viscous material.

As mentioned above, biologically derived scaffold materials may have permeability or porosity that allows water to filter to fully control or regulate intraocular pressure. Permeable biological tissues described herein (e.g., sclera, cornea, collagen, etc.) are preferred scaffold materials, however, any biological tissue, even if impermeable, is considered herein as a potential scaffold material for use as a structural spacer, which keeps the ciliary body separated and open. Preferably, the material of the scaffold can produce a gap that allows fluid to flow. The gap produced can extend longitudinally along each side of the scaffold. If the material of the scaffold is permeable, more fluid can be separated by the ciliary body compared to the situation where the scaffold material is impermeable and the fluid needs to pass along the outside of the scaffold. Therefore, the material considered herein does not need to be porous to provide the desired function, however, the function can be enhanced by the porosity of the material.

Typically, the bioderived stent material has a certain hardness and intraocular durability, so it can maintain outflow from the anterior chamber, however, it is softer than the traditional non-biological derived polyimide shunt (e.g., CYPASS, Alcon) used to treat glaucoma. The stent material can have enough structure to act as a spacer to support the opening of the continuous ciliary outflow. The stent material can maintain its structural height or thickness once implanted in the ciliary body separation, thereby providing a fluid flow through the stent or around the stent. In some embodiments, the cut stent is minimally manipulated by compression or compression into the transmission shaft, so that the size and/or shape of the cut stent is reduced from a first size to a second smaller size in the shaft. The size and shape of the transmission shaft can be designed to be inserted into the anterior chamber through the cornea (e.g., a self-sealing incision in the cornea) and advance toward the iridocorneal angle. The transmission shaft can deploy the compacted stent between the tissue layers close to the angle. Once the compacted stent is deployed from the transmission shaft, it can begin to recover toward its original shape and/or size. Once implanted, the cut stent can take on a shape and/or size that is smaller than its original shape and/or size, or a shape and/or size that is the same as its original shape and/or size. Minimally modified biological tissues can be used to treat glaucoma. Compared to traditional non-biological materials (such as polyimides), biologically derived stent materials offer advantages in biocompatibility, anatomical consistency, and water permeability. Biologically derived stent materials can provide better compliance and conformability to the scleral wall, and are less likely to cause endothelial and scleral erosion/loss over time and with long-term rubbing and blinking of the eye.

Typically, allograft tissue for implantation into the eye is carefully processed so as not to alter its original state. The cut stents described herein do not require such delicate processing, but can be minimally modified by compression or compaction or otherwise wedging into a smaller space for delivery into the eye for intraocular stenting, occlusion, reinforcement, or puncture (less than about 3.5 mm) through a corneal or scleral incision.

In one embodiment, the material for forming the support is provided as a piece of uncut material, which is configured to be manually loaded into the box 200. The piece of uncut material can also be cut by a cutting assembly independent of the box 200, and then transferred to the area of the box 200. As will be discussed in more detail below, the cutting can be performed at the time of surgery or before surgery. In some embodiments, the support is formed by 3D printing and can be printed into the desired final size for the support, or can be printed as a piece of material that is then cut at the time of surgery or before surgery. The cutting achieved by the device described herein can provide a thin strip of material that can be implanted in the eye to provide regulation of water outflow. The process of cutting or trephination can position the cut implant in the catheter or lumen of the box so that the cut implant retained in the box can be subsequently transferred from the conveying device without removing or transferring the cut implant from the box. Alternatively, the cutting can be performed independently of transferring the cut implant to the conveying device. The cutting and transfer of the cut implant to the conveying device can be independent steps performed by independent tools or components. For example, the system can be combined with a first device for cutting a piece of material into a cut implant, a second device for transferring the cut implant into a conveyor, and a third device for deploying the cut implant from the conveyor into the eye. It should be understood that the cutting, transfer, and deployment can be integrated into a single device, or one or more can be separate devices used in conjunction with each other to convert the piece of material into a cut implant for deployment in the eye. In a preferred embodiment, the cutting and transfer of the cut implant are integrated into the first device, and the deployment of the cut implant in the eye is in the second device.

As used herein, the term "patch of material" refers to a piece of biologically derived material that is larger in size along at least one dimension than the size of a stent cut from the patch of material and implanted into a subject. In some embodiments, the patch of material can have a generally square shape, and the stent cut or trepanned from the patch of material can have a generally rectangular shape. For example, the patch of material can be about 7 mm wide x 7 mm long x 0.55 mm thick, and the stent cut from the patch of material can be 0.3-1.0 mm wide x 7 mm long x 0.55 mm thick. The size of the patch of material and the stent cut can vary. The patch of material before cutting can 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 stent cut from the patch of material can be between about 0.3 mm and about 2 mm wide, preferably between 0.7 mm and 1.0 mm wide. The stent cut from the patch of material can be between about 5 mm and about 10 mm long. The stent cut from the piece of the material can be between 0.25mm and about 2mm thick. The piece of material and the stent cut can each have the same length and the same thickness, but the width is different from each other. The piece of material and the stent cut from the piece of material can also have different lengths and thicknesses. For example, the piece of material can have a first thickness and the stent cut from the piece of the material has the same thickness, but can be folded or rolled into a thickness different from the piece of material when implanted. The stent cut does not need to be rectangular in shape, and can have a non-rectangular shape, such as an angle wedge or any shape in a variety of shapes, to provide specific clinical results. For example, a stent cut into a "dog bone" shape with an enlarged distal end and proximal end can provide additional fixation in the target tissue. The stent can be cut into a narrow elongated shape on the front end and has an enlarged size at the tail end to provide convenience for insertion and at least one end of the fixation.

In some embodiments, the piece of material can have a relatively large width (e.g., 10mmx10mm), and the stent is cut from the piece into strips having a much smaller width (e.g., about 1.0mm to about 1.5mm), and the cut stent is then pressed into a delivery conduit having an inner diameter of about 0.8mm so that the width of the stent substantially fills the inner diameter. Even if the stent is not oversized relative to the conduit and therefore remains unpressed, the stent can substantially fill the inner diameter of the delivery conduit. The stent can be oversized relative to the inner dimensions of the conduit and is pressed into the conduit to substantially fill it. In addition, 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 microns to about 800 microns. Therefore, depending on whether the stent is to be pressed into the delivery conduit and depending on the inner dimensions of the delivery conduit, the stent can be cut or trephinated into any of a variety of sizes.

The support cut from the piece of material can have width, length and thickness.In one embodiment, the width of the support cut from the piece of material using cutting device as described herein can be at least 100 microns until about 1500 microns, or between 100 microns to 1200 microns, or between 100 microns and 900 microns, or between 300 microns and 600 microns.The support cut from the piece of material can have a width of at least about 100 microns and be no more than 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, no more than 800 microns, no more than 700 microns, no more than 600 microns, no more than 500 microns, no more than 400 microns, no more than 300 microns or no more than 200 microns.The length of the support cut from the piece of material can vary according to the position of the support implantation.In some embodiments, the length of the support is between 1mm and 10mm, or more preferably between 3mm and 8mm. The thickness of the stent cut from the piece of material can be 100 microns up to about 800 microns, or 150 microns up to about 600 microns. In one embodiment, the biomaterial forming the stent can have a thickness of not less than 100 microns and not more than 5 mm. The thickness of the stent can also depend on whether the stent is folded or rolled up when implanted, so that a piece of material with a thickness of only 250 microns can be cut into the stent and the stent is folded when implanted to double the thickness to about 500 microns. The thickness of the stent can also depend on what biologically derived material is used. For example, scleral tissue or corneal tissue can generally have a thickness of about 400 microns, but can shrink to about 250-300 microns after collection. Therefore, a stent cut from a shrinking corneal tissue piece may only have a thickness of 250 microns.

In some embodiments described in more detail below, a stent cut from a piece of material is cut to substantially fill a conduit through which it is advanced for delivery. In other embodiments, the stent may be cut to an implant that is oversized relative to the size of the conduit through which it is deployed. In this embodiment, the stent may be cut to have a first size that is oversized compared to the internal dimensions of the delivery conduit. The oversized stent may be prepared in a delivery conduit, for example, by compacting or compressing with a tool, so that the stent presents a second, smaller size when prepared in the conduit. After deployment in the eye and the stent is released from the delivery conduit, the stent may achieve a third size that is close to its original first size. This will be described in more detail below.

In a non-limiting example, the biological tissue scaffold has a size of not less than 0.1 mm and not more than 8 mm in any direction and a thickness of not less than 50 microns and not more than 8 mm. In a non-limiting example, the scaffold is about 6 mm long, about 300-600 mm wide, and about 150-600 mm thick. The cut can be not less than 1 mm and not more than 8 mm in any direction. In a non-limiting example, the cut tissue has a size of 100-800 microns wide and 1mm-10mm long. It should be understood that multiple scaffolds can be delivered to one or more target locations during the implantation operation.

Fig. 2 and 6 illustrate an interrelated embodiment of a system 100 for preparing and transmitting a biological intraocular stent to increase water outflow and reduce intraocular pressure. 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 conveying device 400. The cutting device 300 shown in Fig. 2 and Fig. 6 includes an integrated loading feature configured to load the cut stent into the tissue cassette 200 after the stent is cut with the cutting device 300. The system 100 may also be combined with a cutting device 300 (see Fig. 18A-18E and 18F-18H) that does not have an integrated loading component. In this embodiment, the system 100 may include a separate loading device 600 configured to be coupled to the box 200 to load the cut stent produced by the cutting device 300 (see Fig. 19A-19B). Once the stent is cut using the cutting device 300, it may be manually transferred to the loading device 600 from the cutting device 300, for example, using tweezers. The loading device 600 can be used to push the cut stent into the area of the tissue cassette 200 coupled to the loading device 600. The loaded tissue cassette 200 can then be separated from the loading device 600 and coupled to the delivery device 400 for delivery into the eye.

Each system 100 can be provided without a cutting device 300 and only includes a tissue cassette 200 and a delivery device 400. In such an embodiment, the tissue cassette 200 can include a pre-cut stent 105 within the cassette 200, which is ready to engage with the delivery device 400 to be deployed into the eye. The cassette 200 with the pre-cut stent 105 can be immersed in a stable solution. Therefore, where the system is described as including a cutting device 300, it should be understood that the cutting device 300 may not be used during surgery, but rather the stent 105 is provided in at least a portion of the delivery device 400 or the tissue cassette 200 in a pre-cut and/or ready configuration.

FIG. 2 shows a first box 200 shown as being separated from a cutting device 300 and another box 200 with a transfer device mounted thereon. The box 200 is configured to receive a piece 101 of material in the box 200 and to fix the piece 101 of material in preparation for cutting by the cutting device 300. The cutting device 300 is configured to form a biological intraocular scaffold 105 from the piece 101 of material held in the box 200 when operatively engaged with the box 200. The transfer device 400 is configured to transfer the cut implant 105 from the box 200 to an implantation location when operatively engaged with the box 200. The tissue box 200 in the embodiment of FIG. 2 is configured to cooperate with both the cutting device 300 and the transfer device 400 so that the entire tissue box 200 is removed from the two devices 300, 400 of the system 100 and transferred between the two devices 300, 400.

6 shows an interrelated embodiment of the system 100 and includes a tissue cassette 200 configured to be operatively coupled to a cutting device 300 and a transport device 400. However, the entire tissue cassette 200 need not be completely removed from the cutting device 300 in order to be coupled to the transport device 400. In this embodiment, the tissue cassette 200 may include a distal nose cone assembly 274 configured to be separated from the proximal portion 207 of the cassette 200 and coupled to the transport device 400. The nose cone assembly 274 may include at least a portion of the distal portion 205, such as a nose cone 275 and a shaft 210 extending distally from the nose cone 275.

In yet other embodiments, the cartridge 200 need not include a portion configured to receive a piece of material 101 within the cartridge 200. For example, the cartridge 200 may include only a nose cone assembly 274 including a nose cone 275 having a distal axis 210. The nose cone 275 having the distal axis 210 may be coupled to a cutting device 300 configured to receive a piece of material 101 in at least one region and to secure the piece of material 101 in preparation for cutting by the cutting device 300. The nose cone 275 and the distal axis 210 may be arranged relative to the cutting device 300 so that a cut stent may be transferred thereto for deployment into the eye. FIG. 14I schematically illustrates a nose cone assembly 274 coupled to a cutting assembly 500. The nose cone assembly 274 includes a nose cone 275 having a proximal end coupled to the cutting assembly 500 and a distal axis 210 protruding from the nose cone 275 along a longitudinal axis A. The cutting assembly 500 may be a portion of a cutting device 300 as described herein.

The box may include any of a variety of structural arrangements as described herein, but generally refers to a component that can be transferred between two or more devices. The box can be transferred between a cutting device and a conveying device. The box can be configured to hold a piece of material for cutting into a stent and provide a conduit for deploying the stent into the eye. However, the box does not have to be configured to hold a piece of material for cutting. The box may include a shaft that is configured to receive the cut stent from the cutting assembly and then deploy the stent from the shaft into the eye. Any of a variety of configurations are described and contemplated herein.

Each of these systems and their respective components will be described in more detail herein.

Fig. 2 also has Fig. 3A-3C and shows an embodiment of tissue cassette 200, and this tissue cassette 200 is configured to hold the piece of material for cutting and is used to provide the conduit for the stent of cutting to be deployed into the eye.Cassette 200 can include distal portion 205, and this distal portion 205 is connected to proximal portion 207 and extends distally from proximal portion 207. Distal portion 205 can include elongated member or shaft 210, and it has the inner conduit or lumen 238 of size suitable for accommodating and deploying stent 105.Proximal portion 207 can include base 224 and cover 214 that is movably attached to base 224.Proximal portion 207 is intended to remain outside the eye, and distal portion 205 is configured to be inserted into the eye to deploy stent 105 in the target tissue.Implant 105 can be advanced from proximal portion 207 of cassette 200 to the deployment positioned in distal portion 205 of cassette 200. The distal portion 205 of the cartridge 200 can be inserted into the anterior chamber of the eye so that it can be positioned adjacent to 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., coupled to the delivery instrument 400).

Fig. 6 also has Fig. 7A-7C and shows another embodiment of tissue cassette 200, and this tissue cassette 200 is configured to keep the piece of material for cutting, and is used for providing the catheter that the stent for cutting is deployed in the eye.Tissue cassette 200 can comprise distal portion 205, and this distal portion 205 is connected to proximal portion 207 and extends distally from proximal portion 207, and proximal portion 207 comprises axle 210, and this axle 210 has the inner conduit or the inner chamber 238 (visible in Figure 14I) of size for accommodating and deploying stent 105.Proximal portion 207 can also comprise base 224 and the lid 214 that is movably attached to base 224.Distal portion 205 and axle 210 can be removably attached to the proximal portion 207 of cassette 200. For example, the proximal portion 207 can remain within the cutting device 300, while the removable nose cone assembly 274 including the nose cone 275 and the shaft 210 can be separated from the proximal portion 207 and engaged with the delivery instrument 400 (see FIGS. 9A-9D ).

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 the ocular tissue can include the implant 105 being at least partially located between the ciliary body and the sclera of the eye. The implant 105 can be located between the ciliary body and the sclera, within the ciliary body diastasis cleft.

The shaft 210 of the cartridge 200 (also referred to herein as an introducer, applicator, catheter, or delivery body) extending outward in the distal direction 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 so that it may form a distal bend or flexure away from the longitudinal axis A. The distal region 212 of the shaft is a tangent arc of the proximal region of the shaft 210, having a radius between 10-20 mm, preferably about 10-15 mm, or about 12 mm. In some embodiments, the shaft 210 may include a flexible portion and a rigid portion such that the shape of the shaft changes depending on the relative position of these portions. The embodiments shown in FIGS. 3A-3C and 7A-7C have a proximal portion extending along the longitudinal axis A and a distal region 212 that curves downward away from the longitudinal axis A. The distal region 212 may include an opening 230 from the lumen 238 through which the stent 105 may be deployed. The opening 230 from the lumen 238 can 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 lumen 238 can be positioned in a plane that is angled relative to the longitudinal axis A of the distal region 212 of the shaft 210. The distal region 212 of the shaft 210 can be inclined so that the opening 230 into the lumen 238 is elongated rather than circular and the distal-most end 216 of the shaft 210 extends beyond the opening 230. The bevel can be about 10-45 degrees, preferably about 12-16 degrees, or about 15 degrees. The distal-most end 216 of the shaft 210 can be a pointed end or a blunt end (which is square so that it does not form a 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 relative to the longitudinal axis A, the cross-sectional shapes of the opening 230 and the shaft 210 substantially match. If the shaft 210 has a rectangular cross-section and the opening 230 is cut in a manner less than perpendicular to the longitudinal axis A, 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 bevel heel and a second shape near the distal-most end 216. For example, the opening 230 near the bevel heel can be rounded and the opening 230 near the distal-most end 216 can be squared. It should also be understood that the opening 230 need not be located at the distal-most end of the shaft 210. The opening 230 can be formed in the sidewall of the shaft 210 so that the stent 210 is pushed out of the lumen 238 along a direction that is angled relative to the longitudinal axis of the lumen 230. The opening 230 can be positioned in the shaft 210 relative to the box 200 so that it is positioned at the front end, lower side, upper side and/or other side of the shaft 210. The distal region 212 of the shaft 210 can have a cross-sectional shape of a circle, an ellipse, a rounded rectangle, a rectangle, a rounded square, a square, a diamond, a teardrop or other shape, and the distal end 216 has a varying end shape, including a blunt end, a bullet end, a scraper end or a pointed end. The distal region of the shaft 210 can have any of a variety of configurations known in the ophthalmic field.

Axis 210 can be used to produce a ciliary body separation rift in the ciliary body supracavity. The distal region of shaft 210 can be shaped to form a rift and provide a conduit for delivering material to the ciliary body supracavity of the eye. For example, using a pusher as a plunger, shaft 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 the region of the eye by shaft 210 before, during and/or after stent implantation. A corneal incision can be formed with a surgical scalpel or other tool, and shaft 210 is inserted through the incision and the distal end of shaft 210 is navigated to a desired position for delivery. The distal end of shaft 210 can include a scraper that can be used to separate tissue layers and produce a ciliary body separation rift in the ciliary body supracavity between sclera and ciliary body. The size, surface finish and shape of the distal end can minimize trauma. Axis 210 can additionally include one or more marks that provide user information about the insertion distance. The distal region of the shaft 210 may include one or more markings for angulation reference of how deep the tongue of the shaft 210 has been inserted into the supraciliary cavity. The one or more markings may be stamped, etched, or other types of markings as well as one or more fenestrations on the shaft 210, which will be described in more detail below. The length of the shaft 210 is sufficient to allow the device to be used from a temporal or superior position.

The shaft 210 of the cartridge 200 is sized and shaped to be delivered through a clear corneal incision to allow the stent 105 to pass through the distal end of the shaft 210. In at least some embodiments, the distal region 212 of the shaft 210 is sized to extend through an incision of about 1 mm in length. In another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision of no more than about 2.5 mm in length. In another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision of 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 dissection between ocular tissues without penetrating or cutting tissue to position the stent 105. For example, the distal end 216 of the shaft 210 can be configured to bluntly dissect between the ciliary body CB and the sclera S (e.g., the supraciliary space), while the stent 105 remains completely enclosed within the shaft 210 during the blunt dissection. In an alternative embodiment, the distal end 216 of the shaft 210 has a sharp cutting structure for application and implantation through the scleral wall dissection into the subconjunctival space. In yet another embodiment, the distal end 216 can have a cutting structure for dissecting and implanting Schlemm's canal or transscleral implantation.

The shaft 210 can be a hypotube no 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, the shaft 210 is a hypotube having an inner diameter of less than about 0.036" to about 0.009" (0.230 mm - 0.900 mm). The inner diameter of the shaft 210 may be approximately 0.600-0.900 mm. The system may incorporate a 600 micron shaft 210 or an 800 micron shaft 210. Other sizes of shaft 210 are contemplated herein, depending on the specific patient condition and clinical needs.

In a preferred embodiment, the stent described herein can be formed as a solid material strip without any lumen, but it should be understood that the stent may also include a lumen. Therefore, the stent is generally not transmitted by a guide wire like many conventional glaucoma shunts. In addition, the stent described herein can be formed by relatively soft tissue, which is more fragile than a typical shunt formed by a more rigid polymer or metal material. A rigid shunt can be implanted, thereby using the distal end of the shunt to produce a blunt separation at the interface of the tissue through which the shunt is inserted. The stent described herein is preferably deployed using a retractable cannula type syringe or introduction tube, which can be retracted once in an appropriate anatomical position, so that the stent is more gently externalized and precisely positioned. The stent described herein can also be deployed by advancing the pusher distally to push the stent out of the introduction tube. The distal advancement of the pusher can be a slow incremental advancement under direct user control, depending on the degree of depression of the button or the degree of advancement of the slider. The distal advancement can be sufficient to deploy the stent from the lumen into the tissue. In the case where the distal advancement is preferably controlled by the user in a slow, incremental manner, the proximal retraction can be an all-or-nothing sort of actuation achieved by a spring-actuated mechanism. For example, if the user wishes to quickly remove the shaft of the device for any of a variety of reasons other than deploying the stent, the retraction can be relatively quick. The retraction need not result in the deployment of the stent. For example, before the shaft is retracted proximally, the pusher can be withdrawn proximally relative to the stent inside the shaft. If desired, this can withdraw the shaft from the breach while the stent remains in the lumen.

The size of shaft 210 can be selected based on the size required for the stent to be implanted.Stent 105 can have a size that substantially fills the lumen 238 of shaft 210 (or the lumen of at least a portion of shaft 210 through which the stent is transmitted) so that the stent can be pushed distally through the portion.In some embodiments, the stent substantially filled with the lumen is pushed distally without wrinkling or being damaged.In other embodiments, the stent substantially filled with the lumen is pushed distally through shaft 210 in the following manner: the tissue is compacted into a plug, which has a denser structure than the stent when cut from a piece.The size difference or gap between the width and height dimensions of stent 105 and the internal dimensions of the conduit can be up to about 200% of the size of stent 105.The maximum size of the conduit is related to the maximum size 105 of the stent.For example, if the stent width is about 1mm, the maximum size of the conduit can be 3mm, which results in a total gap between the stent width and the outer wall of the conduit being 200% of the stent width.The gap can be less than 5-10% of the maximum size of the stent 105. Generally, the smaller the gap between the stent 105 and the catheter, the better the result 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 cut stent 105, the stent 105 will bend when it is pushed through the shaft 210 for implantation in the eye. The cross-sectional area of the shaft 210 and the cross-sectional area of the stent 105 are preferably substantially matched in size. The catheter can also be coated with a lubricating or low friction material (e.g., Teflon) to improve the advancement of the stent 105 through the catheter during deployment.

The cross-sectional area of shaft 210 may also be smaller than the cross-sectional area of stent 105. As described above, stent 105 may be cut to be oversized relative to the inner diameter of shaft 210 so that stent 105 is compressed, compacted or otherwise minimally manipulated for delivery through a tube. Stents may be cut to have a first size that is oversized compared to the internal dimensions of shaft 210. Oversized stents may be prepared within the shaft, for example, by compacting with a compaction tool or push rod 420, so that stent 105 presents a second, smaller size when prepared within the catheter. When stent 105 is deployed in the eye and released from shaft 210, stent 105 may achieve a third size that is close to its original first size. Delivery and deployment will be described in more detail below.

The shaft 210 can be but need not be completely tubular, and the cross section of the shaft 210 need not be circular. For example, the cross section of the shaft 210 can be circular, oval, square, rectangular or other geometric shapes. In addition, the entire length of the shaft 210 does not need to have the same cross-sectional shape or size. For example, the proximal end of the shaft 210 can have a first shape and the distal end of the shaft 210 can have a second shape. Figures 5A-5B show that the cross section of the shaft 210 is rectangular. The inner cavity 238 of the shaft 210 does not need to be a completely closed channel. For example, the shaft 210 can be combined with one or more fenestrations, openings, segmented windows or have one or more discontinuous walls so that the inner cavity 238 passing through the shaft 210 is a partially closed channel.

One or more interruptions or fenestrations in the shaft 210 may be coated or covered with a material that allows visual inspection of the interior of the shaft 210. FIGS. 16A-16C and 17A-17E illustrate an embodiment of a nose cone assembly 274 configured to be reversibly coupled to a delivery device. As discussed elsewhere herein, the delivery device 400 may include a proximal housing 405 (also referred to herein as a handle or handpiece) and at least one actuator 415. The delivery device 400 may also include a distal side connector 413b configured to be reversibly coupled to the nose cone assembly 274. The nose cone assembly 274 may include a nose cone 275 having a proximal region and a distal region. A connector 413a may be positioned on the proximal region of the nose cone 275, configured to reversibly engage with a distal connector 413b of the delivery device 400. The nose cone assembly 274 may also include a tubular shaft 210 protruding from the distal region of the nose cone 275. The tubular distal shaft 210 may incorporate one or more fenestrations 276 covered by a translucent or transparent material to reveal the lumen 238 of the tubular shaft 210. The one or more fenestrations 276 may form a metering system for the tubular shaft 210 that is configured to identify the insertion depth of the tubular shaft 210 and/or a specific size (i.e., length) of an implant positioned within the lumen 238. The distal nose cone assembly 274 is shown in FIG. 16A and also separated from the delivery device 400 in FIGS. 17B-17C , showing a proximal coupler 413a, which may be a bayonet connector on a proximal region of the nose cone 275 that is configured to reversibly couple to a distal coupler of the delivery device 400. The distal shaft 210 protrudes from the distal region of the nose cone 275.

One or more fenestrations 276 may extend through the area of the distal shaft 210 covered by the transparent material. The fenestrations 276 may be covered by reflowed nylon to form a continuous smooth channel that allows visualization of the interior of the shaft 210. The shaft 210 may include an introduction tube 277 that is at least partially encapsulated by an outer tubular member 278. The introduction tube 277 may be formed of a first material and the outer tubular member 278 may be formed of a second different material. The first material may be stainless steel or nitinol and the second material may be a polymer, such as nylon. The first material may be an opaque material and the second material may be relatively translucent or transparent. The introduction tube 277 may be combined with one or more fenestrations 276 through its sidewall that are covered by the outer tubular member 278 to allow a user to see through the outer tubular member 278 and through the introduction tube 277 to visually inspect the lumen 238 of the introduction tube 277. The fenestrations 276 allow the user to see that the implant is being advanced through the introduction tube 277 when the plunger is actuated through the introduction tube 277. The fenestration 276 can also allow the user to evaluate the implant, such as the length of the implant, before deployment. The fenestration 276 can be a known size or extend a known distance along the introduction tube 277, so that the user can evaluate the length of the implant in the lumen 238 by comparing the size of the implant in the lumen 238 with respect to the known size of (one or more) fenestrations 276. Therefore, the fenestration can form a metering system on the distal shaft, which can be used to understand the insertion depth and/or the length of the implant in the lumen. Each fenestration 276 can be about 2mm-6mm long. The length of the proximal portion of the shaft 210 incorporating (one or more) fenestrations 276 can be between about 4mm and about 8mm. The fenestration 276 can extend through the sidewall on either side of the shaft 210, so that the user can check the lumen 238 from different orientations. The shape and size of the fenestration 276 can vary. In some embodiments, the fenestration 276 is a rectangle as shown in Figure 16A, but they can be any of a variety of geometric shapes. The material of the outer tube member 278 can fill the fenestration 276 of the introduction tube 277 to maintain a smooth and continuous tubular inner diameter. This prevents the implant within the lumen 238 of the introduction tube 277 from becoming stuck or otherwise prevented from sliding through the lumen 238 toward the distal end region 212 of the shaft 210 .

Referring again to FIGS. 16A-16C , the shaft 210 may include a proximal portion extending along the longitudinal axis A and a distal region 212 distal to a fenestration 276 that is curved or bent away from the longitudinal axis A. The distal region 212 of the shaft is a tangent arc of the proximal region of the shaft 210, with a radius between 10-20 mm, preferably about 10-15 mm, preferably about 12 mm. The curved distal region 212 may be incorporated into the shaft 210 with or without a fenestration 276. The fenestration 276 may be positioned along a substantially straight proximal portion of the shaft 210 near the bend or bend. The distal region 212 of the shaft 210 may be translucent or transparent and/or incorporate other windows into the lumen 238 of the shaft 210. In one embodiment, the introduction tube 277 terminates distal to the bend or bend of the shaft 210, and the outer tubular member 278 extends beyond the terminal end of the introduction tube 277 (see FIG. 16C ). Thus, the distal region 212 of the shaft 210 can be formed only by the outer tube member 278. As described above, the outer tube member 278 can be a transparent or translucent material, such as nylon or other polymeric materials that allow visual inspection of the shaft lumen 238. The transparent distal region 212 can be similarly smooth so as to maintain a smooth transition from the metal introduction tube 277 to the polymer distal end. The smooth transition prevents the implant in the lumen 238 from becoming misaligned or stuck during deployment. The distal region 212 can be bent downward from the proximal portion of the shaft 210 so that the distal opening 230 from the shaft 210 is around a longitudinal axis A' different from the proximal opening 280 of the entry shaft 210 that can be around the first longitudinal axis A. The transparent distal region 212 can have a length between about 5mm or about 3mm to about 7mm. The distal opening 230 from the lumen 238 can be angled to increase the size of the opening 230, which can be about 1.5mm to about 2mm. The bevel of the distal region 212 can be between 10-45 degrees, preferably about 12-16 degrees. The distal-most end 216 of the shaft 210 can be formed with a flat surface having a thickness of about 0.10 mm-0.20 mm, preferably about 0.15 mm. Generally, the distal-most end 216 of the shaft 210 is not designed to cut or perforate in ocular tissue, but is used for blunt dissection or separation between tissues. The distal region 212 of the shaft 210 preferably does not contain sharp edges.

As described elsewhere herein, the shaft 210 may include an inner pusher or push rod 420 (see FIGS. 12C-12D and 17E-17I). The push rod 420 may be formed of nitinol, stainless steel, or a monofilament or braided component. The push rod 420 may be a completely cylindrical element without an inner cavity that extends through the inner cavity 238 of the shaft 210 so as to engage against the proximal end of the stent 105. The push rod 420 is flexible enough to translate through the inner cavity 238 of the shaft 210 around the curvature near the distal region, and is also stiff enough to bear against the cut stent 105 within the inner cavity 238 to cause the stent 105 to be deployed in the eye. The push rod 420 may have an outer diameter difference along its length to increase its flexibility relative to the shaft 210, particularly in the case where the shaft 210 has a curved distal region 212. As described above, the shaft 210 may be curved near the distal region to form a tangent arc with a radius between 10-20 mm, or preferably about 12 mm. The geometry of the push rod 420 can be changed over its length to provide improved flexibility to accommodate bending. In one embodiment, the push rod 420 can undergo an outer diameter change between the proximal end and the distal end (see Figure 17F). The distal region 440 of the push rod 420 may have a maximum outer diameter greater than the outer diameter of the middle region 442 of the push rod 420. The smaller outer diameter of the middle region 442 of the push rod 420 is designed to guide the bend of the distal region 212 of the outer shaft 210. The push rod 420 can be reduced between sections so that the outer diameter of each region gradually changes toward the different outer diameters of the adjacent regions. The larger outer diameter of the distal region 440 of the push rod 420 allows a larger surface area to abut the cut stent in the inner cavity 238. If the outer diameter of the distal end 441 of the push rod 420 is too small, the distal end 441 will likely pierce the stent 105 instead of providing a bearing surface against the stent 105. The outer diameter of the distal region 440 can be about 0.525mm-0.575mm, and the outer diameter of the middle region 442 can be narrowed to about 0.200mm-0.300mm. The outer diameters of the distal region and the proximal region can be the same. The length of the middle region 442 can vary, but can be about 8mm-10mm. Typically, the length of the middle region 442 is longer than the length of the distal region 440. The distal region 440 can be about 2mm-5mm. The proximal region 444 of the push rod 420 that is configured to remain within the straight portion of the shaft 210 can be stiffer than the middle region 442 and is designed to be coupled to the actuator 415 on the housing 405 of the delivery device 400. Figure 17G shows the proximal region 444 of the push rod 420 coupled to the actuator 415a of the housing 405.

The box can, but need not be, configured to hold a piece 101 of material prior to cutting with the cutting device 300. The piece 101 of material can be held within the area of the cutting device. Referring again to FIGS. 3A-3C and FIGS. 7A-7C , the proximal portion 207 of the box 200 can include a base 224. The distal region of the base 224 can be coupled to the shaft 210. The proximal region of the base 224 can include a recess 221 configured to receive the piece 101 of material. The recess 221 can include an inverted V-shaped protrusion 271 that protrudes upward from the centerline of the recess 221, which pushes the centerline of the piece 101 of material upward while allowing the sides of the piece 101 of material to hang downward into corresponding channels 270 on both sides of the centerline. FIGS. 7A-7C show that the proximal portion 207 of the box 200 can be reversibly coupled to a nose cone assembly including the shaft 210 and the nose cone 274.

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

The cover 214 is shown in FIGS. 3A-3C as an element that can be completely removed from the base 224. The cover 214 and the base 224 can be optionally connected together by a hinge or other mechanical features. For example, the cover 214 can rotate around the pivot axis of the hinge and remain connected to the base 224 even when in a configuration that exposes the recess 221. FIGS. 7A-7C show that the cover 214 can be switched between an open and closed configuration by applying downward pressure at the front end of the cover 214 (FIG. 7A) to open the cover 214 and applying downward pressure at the rear end of the cover 214 to close the cover 214 (FIG. 7C). For example, the cover 214 can be lifted into an open configuration, exposing the recess 221 of the base 224, and the piece 101 of the material can be positioned in the recess 221. When the cover 214 is positioned back to the closed configuration, the piece 101 can be compressed and/or tensioned between the cover 214 and the base 224. Once the lid is in the closed configuration, the cartridge 200 may be inserted into the receptacle 306 of the cutting device 300 (see FIG. 8 ).

The cover 214 (or some other element) can be configured to additionally apply a certain amount of tension to at least a portion of the piece of material 101, such as by pulling it outward from the centerline of the piece of material 101 before cutting occurs, as described in U.S. Patent No. 10,695,218, issued on June 30, 2020, which is incorporated herein by reference in its entirety.

The piece 101 of material may be inserted into the cassette 200 by the user during surgery. The piece 101 of material may be provided in a size approximating the size of the recess 221 in the base 224. The user may trim the piece 101 of material before installing it in the recess 221. Alternatively, the cassette 200 may be provided pre-loaded with the piece 101 of material located in the recess.

As mentioned elsewhere herein, the cartridge need not be configured to hold a piece of material 101 for cutting by the cutting device 300. Rather, the cutting device 300 can be configured to hold a piece of material 101 for cutting, and then transfer the cut stent to a cartridge coupled to the cutting device 300. FIGS. 10A-10C and also FIGS. 16A, 17B-17C illustrate one embodiment of a cartridge 200 forming a nose cone 274 having a shaft 210 into which the cut stent can be loaded prior to insertion into the eye. The nose cone 274 can be reversibly coupled to the cutting device 300 having an integrated loading component, or can be reversibly coupled to a loading device 600 configured to load the shaft 210 with the cut stent. Once loaded with the cut stent, the cartridge 200 can be removed from the cutting device 300 or loading device 600 so that it can be coupled to the transfer device 400. The cartridge 200 can be positioned relative to a cutting device 300 configured to hold a piece of material 101 and cut it into stents 105. Alternatively, the cartridge 200 can be positioned relative to a loading device configured to receive a cut stent and load the stent into the shaft 210. The coupling between the cutting device 300 (or loading device) and the cartridge 200 can align the longitudinal axis of the distal shaft 210 relative to a region of the device so that the cut stent 105 can be transferred into the distal shaft 210, for example, with a rod or other tool, as will be described in more detail below. The cartridge 200 with the distal shaft 210 with the stent 105 located therein can then be separated from the cutting device 300 or loading device 600 and transferred to a portion of the transport device 400. Thus, the cartridge 200 need not include a portion configured to hold a piece of material 101 for cutting, but rather includes a transferable portion that can alternately couple with a region of the cutting device 300 or loading device 600 and a region of the transport device 400. Where reference is made to a cutting device 300 having an integrated loading component, the cutting device 300 need not be incorporated with a loading component. Rather, a separate loading device 600 may be used that is configured to couple with the cassette 200 to transfer the cut stents into the cassette 200 prior to coupling the cassette 200 with the transport device 400. Each of these embodiments will be described in more detail below.

Fig. 4A-4J also has Fig. 8 and shows the embodiment of cutting device 300, and this cutting device 300 has the cutting assembly for cutting the support from the piece 101 of material.Fig. 14A-14H illustrates the various embodiments of the cutting assembly 500 that can be incorporated into cutting device 300.Cutting device 300 is configured to cut or otherwise prepare the bio-derived tissue of the piece 101 of material with first profile or shape (for example, wider square sheet or piece of material) into the second profile or shape (for example, narrower rectangular material strip) that meets the implantable support 105 with the size described herein.The cutting performed using cutting device 300 as described herein can involve guillotine cutting, punching, rotating, sliding, rolling or pivoting blade cutting motion.In some embodiments, the plane orthogonal to the piece of material performs cutting.In some embodiments, the cutting is performed axially along the catheter of the implant so that the cutting axis can be aligned, in the implant catheter or parallel to the implant catheter to allow unimpeded tissue loading and transfer to implant without manipulation, tearing or damaging fragile support tissue.

As described above, the cutting process is preceded by a tissue fixation step, in which the biologically derived tissue forming the scaffold is securely fixed between two juxtaposed planar surfaces to ensure that the tissue is not wrinkled or deformed and that subsequent cutting has accurate dimensions. The fixation can optionally provide compression and tension or stretching of the tissue in at least one plane to ensure clean cutting of the tissue. The cutting assembly 500 can hold the piece 101 of the material before cutting, or the piece 101 of the material can be kept in the area of the tissue cassette 200 before being cut by the cutting assembly 500. In some embodiments, the cutting device 300 combined with the cover 214 of the cassette 200 can be combined with a front-to-back capture so 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.

The cutting can be performed within a path or conduit formed within the cartridge 200. Thus, the implant 105 cut from the piece of material 101 can be simultaneously or subsequently positioned within or aligned with a conduit for delivery, such that the cut implant 105 can be delivered to the eye via the conduit without the cut implant 105 needing to be transferred from the cartridge 200.

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

4A-4B and also FIG. 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 receptacle 306, which is sized and shaped to receive the proximal portion 207 of the box 200. The inner diameter of the receptacle 306 may be sufficient to receive the outer dimensions of the proximal portion 207 so that the proximal portion 207 can be inserted into the receptacle 306 for a distance. The cover 214 of the box 200 is positioned in the slot 215 to hold the piece 101 of the material in the recess 221. The upper surface of the cover 214 may extend above the upper surface of the base 224 so that the outer dimensions of the proximal portion 207 are keyed. In other words, the outer dimensions of the box 200 are keyed and can only be inserted into the receptacle 306 of the cutting device 300 in a single orientation (e.g., the cover 214 is located on the upper side).

The cutting device 300 may additionally include a cutting assembly 500 having a cutting member 312 configured to cut the piece 101 of material in the recess 221 of the box into a bracket 105 (see FIG. 4C ). The configuration of the cutting member 312 may vary. In this configuration, the cutting member 312 may include at least a first blade 344a and a second blade 344b spaced a distance from the first blade 344a. When the box 200 is mounted in the receptacle 306 of the cutting device 300, the first and second blades 344a, 344b may be positioned above the piece 101 of material. The actuation of the cutting member 312 causes the first and second blades 344a, 344b to be pushed toward the piece 101 of material cut through the thickness, thereby forming the bracket 105. The blades 344a, 344b may have a width along the longitudinal axis A of the box 200 sufficient to cut the full length of the piece 101 of material. The distance between the blades 344a, 344b can be designed to achieve the desired width of the support 105 of the cutting. The blades 344a, 344b can be positioned parallel to each other or can be angled. The blades 344a, 344b can be angled relative to each other and/or relative to the tissue to be cut. Angling the blades improves the reproducibility of tissue cutting, so that a very straight tissue piece is formed from the piece 101, without any ridge along the side of the newly cut support. The angle of the blade will be described in more detail below. The cutting member 312 can also include only a single blade 344, which is configured to trim the support from the piece 101 of material to a certain size. Alternatively, the recess 221 for receiving the piece 101 of material before cutting does not need to be located in the box 200, but can be located in the region of the cutting device 300, which will be described in more detail herein.

In some embodiments, the blades 344a, 344b can be positioned above the piece 101 of material to be cut, and the corresponding lower blades 345a, 345b can be positioned below the piece 101 of material. Thus, when the blades 344a, 344b are pushed downwardly toward the piece 101 of material, they push the piece 101 of material toward the lower blades 345a, 345b, causing the corresponding upper and lower blades to completely cut through the material 101 at two locations, thereby creating a bracket 105.

The cutting member 312 can be actuated by a user to move the blade. The cutting device 300 can include one or more handles 343 that are movably connected to the base 302 to actuate the cutting member 312. The handles 343 can be connected by hinges 317 so that the handles 343 rotate relative to the base 302 around the pivot axis P of the hinge 317. For example, the handles 343 can be lifted to pivot into an open configuration as shown in FIG. 4A and rotated around the pivot axis P back to the cutting configuration as shown in FIG. 4B.

When handle 343 is lifted to open configuration and cutting member 312 is positioned away from cutting configuration, box 200 can be inserted into receptacle 306 of cutting device 300. As best shown in Fig. 4D-4E, box 200 can be slid into receptacle 306 to position recess 221 of sheet 101 of material to be kept below upper blade 344a, 344b and above lower blade 345a, 345b. The cover 214 that sheet 101 of material is kept in recess 221 can include upper part 220, and this upper part 220 tapers to narrower lower part 222. Lower part 222 of cover 214 is aligned with protrusion 271 of recess 221, and sheet 101 of material is stuck therebetween. When box 200 is installed with cutting device 300, upper part 220 of cover 214 can slide above upper blade 344a, 344b. The size of the lower portion 222 of the cover 214 is designed to slide between the upper blades 344a, 344b when the box 200 is inserted into the receptacle 306 of the cutting device 300. Fig. 4D shows that the upper blades 344a, 344b are separated from the lower blades 345a, 345b by a distance, and the narrow lower portion 222 of the cover 214 is located between them. Fig. 4E shows that the handle 343 is rotated downward to return to the cutting configuration, and the upper blades 344a, 344b are pushed downward toward the piece 101 of the material and toward the lower blades 345a, 345. The piece 101 of the material is cut by the corresponding upper blade and the lower blade, thereby forming the bracket 105. The distance between the upper blade and the lower blade determines the width of the bracket 105 cut from the piece 101 of the material.

The handle 343 can be opened in any of a number of orientations relative to the base 302. For example, the pivot axis P of the hinge 317 can be substantially orthogonal to the longitudinal axis of the base A. In this embodiment, the hinge 317 can be positioned on the distal end of the base 302 so that the handle 343 hinges open by rotating upward and toward the distal end of the base 302. The upper blades 344a, 344b can be spring loaded so that they easily return to the open configuration as the handle 343 is lifted or released.

Once the stent 105 is cut, it can be contained on all sides by the box 200 and the cutting member 312, thereby forming a complete enclosure or stent cutting chamber for the stent 105 within the assembly of the cutting device 300 and the box 200. For example, the bottom and top of the stent cutting chamber can be formed by the lower portion 222 of the cover 214 and the protrusion 271 of the recess 221. The walls of the stent cutting chamber can be formed by the upper blades 344a, 344b and the lower blades 45a, 345b of the cutting member 312. Together, the walls of the stent cutting chamber can form a rectangular shape to help constrain and guide the pusher 320 of the cutting device 300, which is advanced to push the stent 105 from the stent cutting chamber to the distal side into the inner cavity 238 of the shaft 210. In one embodiment, the cross-section of the stent cutting chamber can be at least partially arcuate or circular. The upper and lower surfaces of the cutting chamber can be curved or non-planar. As an example, the lower portion 222 of the cover 214 can be concave, forming a concave surface (concavity), forming the arched top of 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 generated around the cut stent 105 relative to the inner wall of the shaft, which may otherwise cause the push rod to deviate from the track or allow the cut stent 105 to deflect away from the desired path during deployment. Minimizing the space in the shaft relative to the trephine stent 105 improves the advancement of the stent 105 through the device. The cut stent 105 can also have a cross-sectional shape that more closely matches the cross-sectional shape of the delivery catheter through which the stent 105 must advance. The corresponding shape eliminates the excess space of the upper and lower sides of the cut stent 105 relative to the catheter. This in turn provides better guidance for the pusher 320 to advance the cut stent 105 toward the distal end of the shaft. The stent 105 may also be cut to be oversized relative to the catheter size, as discussed elsewhere herein, and compressed, compacted, or otherwise manipulated within the catheter prior to deployment.

Once the stent 105 is cut, it can be axially aligned with the lumen 238 of the shaft 210 of the box 200. Figures 4F-4G and 4H-4J show that the cutting device 300 can include a pusher 320 that is configured to slide distally relative to the base 302 into the proximal region of the box 200 to advance the cut stent 105 from the fully enclosed position along the implant catheter into the lumen 238 of the shaft 210. The pusher 320 is not visible in the embodiment of Figure 6. However, the base 302 can include an actuator 304, such as a dial, button, slider or other input, which is operatively coupled to the proximal region of the pusher 320, which moves the pusher 320 distally relative to the base 302 when actuated. Any of the various user actuators 304 is considered herein to move the pusher 320 to position the stent 105 relative to the lumen 238. This preparation step with respect to the pusher 320 of the cutting device 300 ensures that the cut stent 105 is kept in a completely enclosed space on all sides (ie in the area of the shaft 210 ) after the cartridge 200 is removed from the cutting device 300 and before the cartridge 200 is coupled to the transport device 400 .

FIG. 4H shows that the pusher 320 of the cutting device 300 can be advanced distally through the base 302 when the handle 343 is pushed downwardly toward the base 302 (e.g., the blade 344 is positioned in the cutting configuration relative to the implant 105). FIG. 4I shows the pusher 320 ready to engage the stent 105 within the recess 221 on the proximal end. FIG. 4J shows that the pusher 320 has advanced the stent 105 distally into the lumen 238 of the shaft 210 of the cartridge 200. As described above, the blade 344 creates a complete enclosure of the stent 105 for cutting on all sides, except for the upper cover 214 and the lower protrusion 271, preventing the stent 105 from bending within the lumen 238 during this distal advancement into the lumen 238. The catheter in which the stent 105 is held is sized to match (or undersized) the outer dimensions of the stent being implanted, thereby preventing bending and wrinkling when the stent 105 is pushed into the ready position.

The stent 105 can be pushed into the distal region 212 of the shaft 210 and the cartridge 200 removed from the cutting device 300. Once the cutting device 300 and cartridge 200 are separated from each other, the cartridge 200 is ready to be loaded with the delivery device 400 to insert the stent 105 into the eye.

The piece 101 of material can be cut and loaded in the shaft 210 of the box 200 in a variety of ways. As discussed elsewhere, the piece 101 of material can be cut into the same size as the conduit through which the piece 101 of the material will be transmitted. The piece 101 of material can preferably be cut into the size of the conduit slightly larger than the piece of material through which the piece of material will be transmitted, so that the stent 105 is compressed and packed in the conduit, so that it can be more easily advanced through the inner cavity 238. The cutting can be performed as described above with respect to Figures 4A-4E. Other cutting assemblies 500 as described below and with respect to Figures 14A-14H can also be used to perform the cutting of the piece of material and transfer it to the shaft 210. The cutting assembly 500 described herein can form a part of the tissue box 200, the cutting device 300 or the conveying device 400. Preferably, the cutting assembly 500 is a part of the cutting device 300. The cutting device 300 can be coupled to at least a portion of the box 200, such as the nose cone assembly 274, wherein the distal shaft 210 extends from the nose cone 275, so that the cut stent 105 can be prepared in the shaft 210 for delivery using the delivery device 400. The box 200 can include a proximal portion 207 configured to hold a piece of material for cutting, as shown in Figures 2, 3A-3C or 7A-7C, or include a removable nose cone 274 and shaft 210, as shown in Figures 9A-9D, Figure 10A, which does not include a proximal portion 207 for holding a piece of material. The loading of the stent 105 does not need to be performed by the cutting device 300, and the cutting device 300 does not need to engage with the box 200 to load the cut stent into the box. The cut stent 105 can be manually transferred from the cutting device 300 to a separate loading device 600, which is configured to engage with the box 200 and load the cut stent 105 to the box. Whether or not the cartridge 200 is configured to hold a piece of material for cutting, it can be a transferable component designed to be coupled to a cutting assembly, primed with a cut stent, removed from the cutting assembly, and coupled to a delivery device to deploy the cut stent into an eye.

FIG. 14A shows an embodiment of a cutting assembly 500. The cutting assembly can be a portion of a cutting device 300 configured to engage with a cartridge. The cutting assembly 500 can also be a separate component of a tissue preparation system that is configured to hold a piece 101 of material and cut the piece 101 of material, but is not configured to load the cut stent into a delivery shaft. The cutting assembly 500 can cut a piece 101 of material that can be held within a cartridge or within the region of the cutting assembly 500. The cut stent can be transferred from the cutting assembly 500 to the distal shaft 210 of the cartridge 200 for delivery through the shaft into the eye. The cut stent can be transferred from the cutting assembly 500 manually, for example with forceps, to a loading system configured to load the cut stent into the distal shaft 210. The cutting assembly 500 can incorporate a cutting die 511 positioned relative to a slot 507 in a base 509 and a movable member 505 having a planar bearing surface 513 coupled to the base 509. The movable member 505 can be rotated 90 degrees relative to the base 509 from the first position to the second position. When the movable member 505 is rotated to its second position, the piece 101 of material can be placed against the load-bearing surface 513. The cutting die 511 can press the piece 101 of material against the load-bearing surface 513. Pushing the cutting die 511 toward the load-bearing surface 513 can cut through the piece 101 of material at two positions (e.g., at one or two positions, as described elsewhere herein). Excess tissue can be removed from the load-bearing surface 513, and the movable member 505 that still holds the cut stent 105 on its load-bearing surface 513 is swung toward the first position. This arranges the cut stent 105 on the load-bearing surface 513 within the path of the slot 507 so that the clamping tool 517 or other member can load the cut stent 105 into the slot 507. The slot 507 may have a terminal region 508 that is aligned with the longitudinal axis A of the distal shaft 210 when the cartridge 200 is coupled to the cutting device 300. The cut stent 105 may be pushed by a compression tool 517 at an angle to the longitudinal axis of the shaft 210 (e.g., orthogonal to the longitudinal axis of the shaft 210). The terminal region 508 may have a circular cross-sectional shape similar to the cross-sectional shape of the distal shaft 210. The cut stent 105 positioned in the terminal region 508 may then be pushed into the lumen of the distal shaft 210 so that it is ready for delivery. The size of the slot 507 and/or the terminal region 508 may be smaller than the size of the cut stent 105 so that the advancement of the compression tool 517 pushing the cut stent 105 into the slot 507 causes the stent 105 to be compressed and compacted into a plug. Once the cut stent 105 is positioned within the distal shaft 210 of the cartridge 200, the cartridge 200 can be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye. Cutting, transfer, loading, and preparing can be combined into a single assembly or into separate components configured to work in conjunction with each other.

FIG. 14B shows an embodiment of the interrelationship of a cutting assembly 500 for cutting a piece 101 of material and transferring the cut support 105 for transport. As with the embodiment of FIG. 14A , the cutting assembly 500 can be part of a cutting device 300 configured to engage with a box. The piece of material can be held in the area of the box for cutting, or can be held by a portion of the cutting assembly 500. A cutting die 511 can be inserted through a movable element 515 (referred to herein as a door, pad, or other component) to cut the piece 101 of material. The pad 515 can be configured to hold the tissue below it, apply pressure to the tissue below it, and/or compress the tissue below it. The piece 101 of material can be positioned against a bearing surface 513. The bearing surface 513 need not be part of a movable member as in the previous embodiment, but can be at least a portion of a base 509. The piece 101 of material can be compressed between the bearing surface 513 of the base 509 and the pad 515. The cutting die 511 can be advanced through the pad 515 so that the (one or more) blades of the cutting die 511 cut through the piece 101 of material. If the cutting die 511 has two blades (e.g., two blades as shown in Figures 14A-14B, 14E, 14F-1 and Figures 18E-18G, 22A and 23C), the cutting die 511 cuts through the piece 101 at two locations. If the cutting die 511 has a single blade, the cutting die 511 cuts through the piece 101 at a single location. In the case of two blades, the blades can be positioned parallel to each other or can be angled. Angling the blades improves the reproducibility of tissue cutting, so that a very straight piece of tissue is formed from the piece 101 without any ridges along the sides of the newly cut support. The angling of the blades will be described in more detail below.

After the piece 101 of material is cut, excess tissue can be removed and the pressure applied by the pad 515 is released. The cutting die 511 can include a spring 516 so that it returns to its initial position and the pad 515 and the cutting die 511 no longer apply pressure to the cut stent 105. The cut stent 105 can be positioned relative to the slot 507 in the base 509 so that the compression tool 517 can push the cut stent 105 through the slot 507 toward the terminal area 508. The positioning of the stent 105 can be performed manually by the user, such as using forceps or using a tool that is part of the cutting/loading system. Figure 14B shows the loading of the cut stent 105 into the catheter from the side of the shaft 210 or orthogonal to the axis of the shaft 210. As discussed elsewhere, the cut stent 105 can be oversized relative to the size of the slot 507 so that pushing the stent into the catheter will compress and compact the stent 105 for delivery. The slot 507 can have a terminal region 508 that is aligned with the longitudinal axis A of the distal shaft 210 when the cartridge is coupled to the cutting device 300. The cut stent 105 positioned within the terminal region 508 can then be pushed into the distal shaft 210 so that it is ready for delivery. The cut stent 105 can be positioned within the terminal region 508 by pushing the stent in a first direction (e.g., transversely relative to the longitudinal axis of the shaft 210), and then positioned within the distal shaft by pushing the cut stent 105 in a second direction (e.g., along the longitudinal axis of the shaft 210). The cartridge containing the cut stent 105 can now be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye.

FIG. 14C shows an interrelated embodiment of a cutting assembly 500 for cutting a sheet of material 101 and transferring the cut stent 105 for transport. The cutting assembly 500 may additionally incorporate a movable stopper 520 positioned between the sheet of material 101 and the slot 507 through which the cut stent 105 is to be advanced. The pad 515 and cutting die 511 may press the sheet of material 101 against the bearing surface 513 of the base 509. The sheet of material 101 may be enclosed between the bearing surface 513 on the lower side, the movable stopper 520 on the far side, and the pad 515 on the upper side. The cutting die 511 may include a single blade (or two blades) and be advanced through the compressed sheet of material 101 to cut the sheet at a single location, thereby producing the stent 105. The cutting die 511, pad 515 and movable stop 520 can be withdrawn away from the cut stent 105 so that the clamping tool 517 can push the cut stent 105 distally into the slot 507 for delivery. When the cartridge is coupled to the cutting device 300, the terminal region 508 of the slot 507 can be aligned with the longitudinal axis A of the distal shaft 210. The cut stent 105 located within the terminal region 508 can then be pushed into the distal shaft 210 so that it is ready for delivery as described elsewhere. FIG. 14I shows a nose cone assembly 274 arranged relative to the cutting assembly 500 of FIG. 14C. The longitudinal axis A of the distal shaft 210 of the nose cone assembly 274 can be aligned with the terminal region 508 of the slot 507 so that the clamping tool 517 can push the cut stent 105 into the shaft 210. Once the cut stent 105 is compacted into the lumen 238 of the shaft 210, the nose cone assembly 274 may be removed from its association with the cutting assembly 500 and transferred to the delivery device 400 for deployment into the eye.

The position of the movable stop 520 relative to the cutting blade of the die 511 can be adjusted to achieve different stent widths. For example, the movable stop 520 can be moved toward the single blade of the cutting die 511 to reduce the width of the stent, and can be moved away from the cutting die 511 to increase the width of the stent. The position of the movable stop 520 relative to the cutting die 511 can be selected by a user, for example, via a dial or other user interface that allows incremental adjustment. The dial range can be between about 0.6 mm and about 1.9 mm, and can include markings arranged in 1/4 to 1/16 thread arrangements. As described elsewhere herein, the cutting die 511 of the cutting assembly 500 can be attached to a rod, handle, or other actuator 343 to advance the single blade through the piece 101 of material held against the bearing surface 513 by the pad 515 when the width is selected. In one embodiment, the bearing surface 513 can be a soft plastic material (e.g., 1/16" 90A silicone).

15A-15B illustrate a trephine or cutting device 300 having a cutting assembly 500. The cutting device 300 may include a handle or actuator 543 that is movably coupled to a base 509 to actuate the cutting assembly 500. For example, the actuator 543 is configured to raise and lower the cutting die 511 relative to the bearing surface 513 of the base 509. The configuration of the actuator 543 may vary as described herein, including levers or scissoring handles.

In other embodiments, the actuator 543 is a rod configured to be raised and lowered to engage with the cutting die 511 located above the bearing surface 513 of the base 509. The actuator 543 may have a lower surface configured to press against the upper surface of the cutting die 511 so as to push it downward toward the bearing surface 513 of the base 509. The rod may provide a mechanical advantage for pressing down the cutting die 511, but it need not be part of the cutting device 300. In some embodiments, the upper surface of the cutting die 511 may form a button that is configured to be directly manually actuated to cut the support. The bearing surface 513 is preferably a planar surface configured to keep the piece of material flat for cutting. The bearing surface 513 may be a recess 544 in the base 509 that is sized to hold a piece of material (not shown). The bearing surface 513 may be movable relative to the base 509 to expose the recess 544 so as to position the piece of material 101 in the recess 544.

In some embodiments, the cutting die 511 includes a single blade that is movable to select the size of the stent being cut. The cutting device 300 may be combined with an actuator 545, such as a dial, a button, a slider, a switch, or other types of actuators configured to adjust the position of the die 511 relative to the bearing surface 513 as described above. The actuator 545 can move the base 509 left and right through a threaded screw or other mechanism to change the position of the piece 101 of the material on the bearing surface 513 (e.g., held in the recess 544) relative to the cutting die 511, and thereby modify the width of the stent cut from the piece. Alternatively, the actuator 545 can move the die 511 relative to the bearing surface 513 to change the width of the stent. The cutting device 300 may be combined with a workbench 546, which is configured to be movable relative to the base 509, such as by sliding, rotating, or lifting from the base 509. In some embodiments, the workbench 546 can slide in a single plane relative to the underlying base 509 while remaining at least partially connected to the base 509. Alternatively, the table 546 can be completely removed from the base 509. Moving the table 546 relative to the base 509 can reveal the recess 544 below the device area where the cutting mold 511 and the actuator 543 are located. This allows the loading of the piece on the load-bearing surface without obstructing the user's view or physically blocking access by the components of the cutting assembly 500. The cutting device 300 can be a separate cutter and does not need to be combined with a compression or retention mechanism or a transfer mechanism. Instead, the cut stent 105 cut with the cutting assembly 500 can be manually transferred to other tools for preparing the cut stent 105 to be deployed through the shaft. The cutting device 300 can be a micro-trephine device for minimal modification of biologically derived tissue. The device 300 is configured to cut biologically derived tissue into elongated tissue strips having a length greater than the width. The width can be less than about 3 mm and the length can be greater than about 3 mm. The biologically derived tissue can be any of the various tissues described herein, including scleral tissue or corneal tissue collected from a donor of a patient receiving a tissue strip as an implant. The cutting die 511 may include a single sharp edge to trim a larger portion of biological tissue to a desired width. The sharp edge of the die 511 may be substantially straight so that the die 511 can cut a certain length of tissue. Alternatively, the cutting die 511 may be combined with two sharp edges parallel to each other, the two sharp edges being separated by a corresponding width to achieve the desired width of the scaffold.

The cutting die 511 may include a single blade with a sharp edge or two blades each with a sharp edge. The sharp edge may be formed by a single distal bevel or a double distal bevel. The two blades may be spaced apart from each other in a precise manner so as to cut a piece of material in a single cutting actuation of the cutting die 511. The two blades may be spaced apart parallel to each other. In a preferred embodiment (best shown in Figures 22B-22C), the blades may be installed at an angle to each other, and the angle may be adapted to the angle of the distal bevel to ensure that the internal spacing between the blades formed by the distal bevel is parallel to each other or orthogonal to the bearing surface. Various embodiments of the cutter described herein may include two blades positioned angularly in this manner. In the case where the cutter is described as having a single blade, the cutter may also include a double blade spaced apart by a certain distance. And in the case where the cutter is described as having a double blade spaced apart by a certain distance, the blades may be positioned at an angle relative to each other so that their bevels are arranged parallel to each other.

FIG. 14D shows an embodiment of the interrelationship of a cutting assembly 500 for cutting a piece 101 of material. The cutting assembly 500 may include a paper punch type cutter. The left side of FIG. 14D shows the cutting assembly from a top view and also shows the cutting assembly from a cross-sectional view. A sharp edge 525 of a point or projection may protrude from the bearing surface 513. The sharp edge 525 may surround a hole 527 through the bearing surface 513 that directly leads into the slot 507 of the base 509. The piece 101 of material may be positioned against the bearing surface 513 above the hole 527 and against the sharp edge 525. The punch 511 may be pushed from above against the piece 101 of material so that the piece 101 of material is cut by the sharp edge 525 and the cut bracket 105 is pushed by the punch 511 through the hole 527 into the slot 507. The cut stent 105 can then be arranged within the slot 507 so that a pusher (not shown in FIG. 14D ) can push the cut stent 105 through the slot 507 toward the end 508. The terminal region 508 of the slot 507 aligns the cut stent 105 with the longitudinal axis A of the distal shaft 210 so that the stent can be pushed into the distal shaft 210 so that it is ready for delivery. The cartridge can be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye.

FIG. 14E shows an interrelated embodiment of a cutting assembly 500 for cutting a piece of material 101. The cutting assembly 500 can also incorporate a money plunger type of cutting. The piece of material 101 can be positioned above the slot 507 in the base 509, and the cutting die 511 is pushed against the material 101 from above so that the cutting edge of the die 511 can cut through the piece of material 101 at two locations to cut out the length of the cut stent 105. The compacting tool 517 can be pushed through the orifice 529 in the die 511 to drive the cut stent 105 into the slot 507, thereby pushing it to the terminal area 508 of the slot 507. The compacting tool 517 or another compression tool 421 can be pushed through the hole 529 in the die 511 to compress the cut stent 105 within the terminal area 508 of the slot 507 to compact it and align the cut stent 105 with the distal shaft 210 so that it is ready for delivery. The cartridge may be removed from the cutting device 300 and transferred to a delivery device 400 for deployment into the eye.

14F-1 to 14F-2 illustrate an interrelated embodiment of a cutting assembly 500 for cutting a piece 101 of material. The cutting assembly 500 may be combined with a pliers-like tool 530 to clamp the piece 101 of material. A surgical scalpel or other cutting tool 535 may be used to trim the piece 101 of material held by the pliers 530 to a certain length. The pliers 530 holding the cut stent 105 may be arranged relative to the base 509, and the clamping pressure of the pliers 530 is released. A compacting tool 517 may be advanced through the pliers 530 to push the cut stent 105 from the pliers 530 into the slot 507 of the base 509 for compressing and compacting the cut stent 105 for delivery as described above.

14G shows an interrelated embodiment of a cutting assembly 500 for cutting a piece of material 101. The cutting assembly 500 can 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 can be trimmed to size with a surgical scalpel or other cutting tool 535. The cut stent 105 within the transfer slot 537 can be transferred by attaching the transfer base 539 to a base 509 having a defined slot 507 in the following manner: aligning the transfer slot 537 with the slot 507 so as to compress and load the cut stent 105 using a compression tool 517 for deployment.

FIG. 14H illustrates an interrelated embodiment of a cutting assembly 500 for cutting a piece 101 of material. The cutting assembly 500 may incorporate a rotating cylinder 540 configured to cut and arrange the cut stent 105 relative to the slot 507 in the base 509 for loading and compressing the stent 105 for transport. The rotating cylinder 540 may incorporate an internal slot 542 for receiving at least a portion of the piece 101 of material. The rotation of the cylinder 540 trims excess tissue extending beyond the slot 542 in the cylinder 540. The cut stent 105 trimmed to length within the slot 542 of the cylinder 540 is then arranged relative to the slot 507 in the base 509 for loading and compression for transport.

18A-18H illustrate another embodiment of a cutting device 300, which is also referred to herein as a trephine box. The cutting device 300 may include a base 302 coupled to an actuator 343. The actuator 343 may be a rod configured to rotate about a pivot axis of a hinge 317. The actuator 343 is configured to actuate a cutting assembly 500 of the cutting device 300 to cut the piece 101 into a bracket 105. The cutting assembly 500 may include a cutting die 511 attached to at least one blade 547 and a pad 515 movably coupled to the base 302. The cutting die 515 may be movable relative to the pad 515 so that the blade(s) 547 may be moved between a retracted position and an extended position. When in the retracted position, the blade(s) 547 remain closed within the pad 515. When in the extended position, the blade 547 penetrates the hole 527 in the pad 515 and extends through to the lower surface of the pad 515. The base 302 may include a bearing surface 513 positioned below the location of the hole 527 so that the blade(s) 547 are urged against the bearing surface 513 when the cutting die 511 is actuated. The bearing surface 513 may be located in a recessed area of the base 302 that is shaped and sized to receive a piece 101 of material to be cut into a stent by the blade(s) 547. The recessed area of the base 302 may be positioned relative to the hole 527 so that a desired stent width is obtained when the piece is cut with the blade 547. The area of the recessed bearing surface 513 may extend beyond the edge of the hole 527 by a distance equal to the desired width of the cut stent. The user may place the piece of material in the recessed area so that the edge of the material abuts the distal end of the recessed area so that when the blade(s) 547 extend through the hole 527 and abut the bearing surface 513, the piece is cut to the desired width. The area of the base 302 that holds the piece need not be concave, but is preferably planar so that the piece of material 101 is relatively flush with the base 302 and substantially orthogonal to the blade during cutting.

The pad 515 may be referred to as a door, pressure pad, or compression element and may be coupled to the base 302 so that it articulates between an open configuration as shown in FIGS. 18C-18D and a closed configuration as shown in FIGS. 18C-18D. As shown in FIGS. 18A-18B. The open configuration reveals the bearing surface 513 of the base 302 so that the tissue piece 101 may be positioned against it. The pad 515 may articulate to a closed configuration above the tissue piece 101. FIG. 18E shows the piece 101 positioned against the bearing surface 513 of the base 302 below the hole 527 in the pad 515, with the edge of the piece 101 against the end of the recessed area. The blade(s) 547 of the cutting die 511 are in a retracted configuration. One or more leaf springs 516 may push the cutting die 511 upward away from the base 302 so that the blade(s) 547 are retracted into the pad 515. The handle 343 in the open configuration to load the piece 101 may articulate to a closed configuration above the cutting die 511. The handle 343 is articulated so that its lower surface presses against the upper surface of the cutting die 511, pushing the cutting die 511 downward and compressing the spring 516. The pad 515 can be fixed and press the piece 101 against the load surface 513 before actuating the (one or more) blades 547 of the cutting assembly 500. The handle 343 can additionally apply pressure on the piece 101, urging it against the load surface 513. The (one or more) blades 547 of the cutting die 511 travel through the holes 527 and penetrate the piece 101 to form the cut stent. When the handle 343 is released, the spring 516 pushes the cutting die 511 upward, causing the (one or more) blades 547 to move away from the load surface 513 and back into the holes 527 of the pad 515. The handle 343 can be articulated to an open configuration, and the pad 515 can be articulated to an open configuration to reveal the cut stent in the recessed area of the base 302. The cut stent can be manually transferred to the loading device 600.

As described above, the cutting die 511 may include a pair of blades 547. The blades 547 may be spaced apart from one another in a precise manner so as to cut the piece 101 of material in a single cutting actuation of the rod 343. The blades 547 may be spaced apart parallel to one another. In a preferred embodiment, the blades 547 are mounted at an angle to one another. The angle between the blades 547 accommodates the angle of the bevel at the distal cutting edge of the blades 547, ensuring that the interior space between the blades 547 (at least the portion of the blades 547 that penetrates the tissue) is parallel and straight.

Each blade 547 comprises a sharp distal cutting edge formed by at least one distal bevel. Two blades 547 are installed at an angle relative to each other so that the inner faces are not parallel and the distal bevels are parallel to each other. As described in more detail below, although the inner faces of the blades 547 themselves are not parallel, the distal bevels of the blades 547 are parallel to each other and substantially orthogonal to the plane surface of the bearing surface, so the tissue piece is cut. The angle of the blade is described in more detail below with reference to Figures 22B-22E and Figures 23A-23C. The embodiment of the blade box with angled blade described below is relevant to the blade of the cutting die of the embodiment shown in Figures 18A-18H etc.

Figure 18F is a related embodiment of the cutter of Figures 18A-18E. Figure 18G is a cross-sectional view of the cutting device 300 of Figure 18F taken along line G-G. Figure 18H shows the dual angled blade 547 of the cutting device 300 with the upper half of the device including the rod actuator 343 removed.

Similar to the embodiment in FIG. 18A , the cutting device 300 includes a base 302 coupled to an actuator 343. The actuator 343 may be a rod configured to rotate about a pivot axis of a hinge 317. The actuator 343 is configured to actuate a cutting assembly 500 of the cutting device 300 to cut the piece 101 into the bracket 105. The cutting assembly 500 may include a cutting die 511 attached to at least one and preferably two blades 547. The cutting die 511 and the blades 547 may be coupled to a pad 515 that is movably coupled to the base 302 about the hinge 317. In some configurations, the cutting die 511 and the attached blades 547 may be movable relative to the pad 515. In other configurations, the cutting die 511 and the attached blades 547 are fixed relative to the pad 515 so as to move with the pad 515 about the hinge 317. The blades 547 may, but need not, be completely enclosed within the pad 515 prior to cutting actuation. The blade 547 can extend through the lower surface of the pad 515 (either by actuation or simply by being fixed relative to the pad 515 in such a manner) so that the blade 547 can be pushed against the load-bearing surface when the cutting die 511 is actuated (not shown in Figures 18G-18H).

The bearing surface 513 is sized and shaped to receive the piece 101 of material to be cut into the bracket by the blade 547, and the bearing surface 513 can be located in the recessed area 544 of the base 302. The bearing surface 513 can be a removable planar element that is configured to be fixed to the base 302 relative to the blade 547 to support the piece 101 of material. The coupling of the bearing surface 513 to the base 302 can be reversible, so that the bearing surface 513 can be replaced over time if necessary without having to deal with the entire cut. The bearing surface 513 can be coupled to the base 302, for example, by one or more fasteners (such as screws). Figures 18G-18H show two holes 541 located near the recessed area 544 of the base 302, which are sized to receive screws 549 that fix the bearing surface relative to the base 302. Other mechanisms to ensure that the bearing surface 513 remains in place within the base 302 are also considered to include a tool-free snap fit or interference fit between the removable bearing surface 513 and the base 302. The planar bearing surface 513 is preferably positioned orthogonal to the sharp edge of the blade 547 during use, as will be described in more detail below. The blade 547 may also be removably attached to the pad 515 so that the blade 547 may be replaced if necessary if the cutting edge of the blade 547 has become dull.

The pad 515 is coupled to the base 302 so that it articulates between an open configuration and a closed configuration about a hinge 317, as described above with respect to FIGS. 18A-18E. The open configuration reveals the bearing surface 513 of the base 302 so that the piece 101 can be positioned against the bearing surface 513 within the cutting device 300. The pad 515 can be articulated to a closed configuration so that the blade 547 is located above the piece 547. In some embodiments, closing the pad 515 relative to the base 302 can hold the piece 101 (with or without compression or pressure) within the cutter 300 until actuation of the rod 343 relative to the pad 515 causes the blade 547 to cut through the piece 101. The return spring 516 can push the rod 343 and the cutting die 511 with the attached blade 547 upwardly away from the bearing surface 513 of the base 302. The return spring 516 thus slightly retracts the blade 547 relative to the pad 515. The rod 343 is movable about the pivot axis of the hinge 317 to close the pad 515 relative to the base 302. The rod 343 is also movable about its own pivot axis of the second hinge 318 to move relative to the pad 515. This articulation relative to the pad 515 causes the blade 547 to completely cut the tile 101 because the blade 547 is completely pushed against the bearing surface 513. Thus, the pad 515 can be used to close the cutting device 300 and fix the tile relative to the base 302 before the actual cutting, which can occur when the rod 343 is further actuated relative to the pad 515 about the axis 318. The blade 547 of the cutting die 511 can travel further downward relative to the bearing surface 513 to form a cut bracket from the tile 101. When the rod 343 is released, the spring 516 pushes the cutting die 511 upward, so that the blade 547 is moved away from the bearing surface 513. The rod 343 can be articulated about the axis 317 back to the open configuration, thereby opening the pad 515 and revealing the bearing surface 513. The cut stents can be manually transferred to a loading device, such as the loading devices described herein.

In other embodiments, the blade 547 is fixed relative to the pad 515 so that merely closing the pad 515 relative to the base 302 causes the cutting edge of the blade 547 to pierce and cut the tile 101. The user can actuate the cutting device 300 using the lever 343. The pad 515 can be rotated about the pivot axis of the hinge 317 by the lever 343 to close the pad 515 relative to the base 302. The lever 343 can be moved relative to the pad 515 to rotate about the pivot axis of the second hinge 318. This movement compresses the return spring 516 and applies a certain amount of cutting pressure to the pad 515, pushing it toward the tissue on the bearing surface 513. The return spring 516 in this configuration provides a tactile feeling to the user that prevents the user from pressing the pad 515 too close to the bearing surface 513 and causing damage to the cutting edge of the blade 547. The movement of the lever 343 relative to the pad 515 provides the user with some feedback that they have reached the end of the travel of the pad 315 to prevent inadvertent damage to the blade 547 during cutting.

The blades 547 can be installed at an angle relative to each other to accommodate the angle of the bevel of the distal cutting edge. The installation angle of the blades 547 ensures that the cutting edges are spaced parallel to each other and are in a straight face and orthogonal to the load-bearing surface 513. Figure 18H shows a spacer 526 positioned between the blades 547, which provides the angle of the blades 547 relative to each other. The angle of the blades 547 relative to each other and the geometry of their cutting edges will be described in more detail below with reference to Figures 22A-22E and Figures 23A-23C. The description of the blade 712 shown in these figures is relevant to the blade 547 of Figures 18A-18E and the blade 547 of Figures 18-18H.

The cutting die 511 may include an ejection spring 531 located between the blades 547. The ejection spring 531 helps eject the cut stent 105 from between the blades 547 after the cutting action is completed. Ejecting the cut stent 105 from between the blades 547 allows the user to more easily grab the cut stent 105, such as with tweezers, to load the stent into the conveyor. The spring 531 may be a coil spring, leaf spring, foam, or other spring mechanism that helps push the stent 105 out from between the two blades 547. The ejection spring is described and shown in more detail below in Figures 23A-23C.

Figures 21A-21B show an interrelated embodiment of a trephine or cutting device 700 having a blade box 710 having at least one and preferably two blades 712. The two blades 712 allow a user to cut a piece of material 101 at two locations of the piece of material 101 in a single actuation to form a bracket 105. The blade box 710 may include an upper component or jaw 714 and a lower component jaw 716. The upper jaw 714 may include the blade 712 and the lower jaw 716 may include a bearing surface 715. The bearing surface 715 is a planar surface that is designed to hold the piece of material 101 in a flat orientation relative to the blade 712 so that it can be cut when actuated. The relative position terms "upper" and "lower" are used to clearly illustrate the orientation of the components relative to each other and are not intended to be limiting. For example, as shown in the embodiments of Figures 18A-18H and 21A-21B, the blades may be positioned on the upper component and above the lower component. Alternatively, the blade may be positioned on the lower component and below the upper component.

The cutting device shown in Figures 18A-18H has an actuator configured to cause a blade to cut a piece of material into an implant. The actuator is a rod 343 configured to move a cutting die 511 relative to the piece. The cutting device shown in Figures 21A-21B also has an actuator configured to cause a blade to cut a piece. In this embodiment, actuation is achieved using a scissor-type handle 705 that is reversibly coupled to a blade box 710. For example, the handle 705 may include a first handle portion and a second handle portion that are coupled together in a scissor-type arrangement by a hinge. The scissor design of the handle 705 opens the blade box 710 attached to the handle 705 when the handle 705 is unfolded, and closes the blade box 710 when the handle 705 is returned to the closed configuration. Opening the blade box 710 separates the upper jaw 714 of the blade box 710 from the lower jaw 716, revealing the bearing surface 715 of the lower jaw 716. This allows the piece 101 of the material to be placed on the bearing surface 715 before cutting. After the piece 101 of material is positioned on the load-bearing surface 715, closing the blade box 710 causes the upper jaw 714 to approach the lower jaw 716 of the blade box 710, until the blade 712 pierces the piece 101 of the material on the load-bearing surface 715. The actuation of the cutting device described herein can be varied, including the scissor-type actuation of the handle and the actuation of moving the cutting die using a rod, as described about Figure 18A-18H. It should be understood that the blade box shown in Figure 21A-21B can also be actuated using a rod system similar to Figure 18A-18H, and vice versa. Any one of a plurality of cutting actuations is contemplated herein.

The bearing surface 715 can be a soft plastic material (e.g., silicone with a Shore 90A hardness) configured to prevent the blade 712 from becoming dull or damaged. The bearing surface 715 can incorporate one or more markings to help guide the user to cut the tissue into a desired shape.

The relative configuration of the blade 712 and the bearing surface 715 can vary. For example, the blade 712 can be located on the upper jaw or the lower jaw, while the bearing surface 715 is located on the opposite jaw. The scissor handle 705 of the trephine device 700 can be universal in that the device 700 can be used by both right-handed and left-handed users.

As mentioned above, blade box 710 can be removably mounted on handle 705. This allows to discard blade when cutting edge becomes dull. Blade box 710 can be removed from handle 705 and replaced with a new blade box 710 with a recent and sharp blade 712. Similarly, the cutting die 511 in the embodiment shown in replaceable Figure 18E. Cutting assembly 500 includes a cutting die 511 with at least one blade 547, and blade 547 is configured to move relative to pad 515 and bearing surface 513 when actuated by rod 343. Cutting die 511 can be removed from pad 515 together with (one or more) blades 547 attached thereto, so that when (one or more) blades 547 become dull, mold 511 can be replaced with a new mold 511 with a recent blade 547.

FIG. 21A shows a trephine device 700 with a blade cartridge 710 mounted on a handle 705, and FIG. 21B shows the blade cartridge 710 removed from the handle 705. Each handle portion of the handle 705 may include a rod-shaped projection 707 at its distal end, the size, shape, and length of which are configured to receive corresponding holes 708 of an upper jaw 714 and a lower jaw 716 extending from at least the proximal end toward the distal end through the blade cartridge 710. The first handle portion has a first projection 707 configured to be inserted into the hole 708 of the lower jaw through the proximal opening, and the second handle portion has a second projection 707 configured to be inserted into the hole 708 of the upper jaw through the proximal opening. The hole 708 may be positioned through an area of the jaws that avoids interfering with the cutting of the blade 712. Spreading the handle portions separates the projections 707 in a scissor-like motion and thus separates the jaws. The attachment between hole 708 and projection 707 can be combined with the feature that is configured to provide reversible, tool-free engagement between them, including sliding fit, interference fit, snap fit, bayonet and other types of attachment. It is expected that the jaws 714, 716 of blade box 710 are prevented from rotating relative to their corresponding projection 707 to ensure that blade 712 and bearing surface 715 remain perpendicular to each other. Projection 707 is shown as having a square cross section to prevent the jaws 714, 716 of blade box 710 from rotating around the axis of projection 707. In an embodiment, attachment is a sliding fit or interference fit on projection 707, which prevents blade box 710 from rotating after attachment. Consider any one of a variety of shapes (e.g., oval, rectangular, triangular or other non-circular geometric shapes). As known in the art, the attachment between handle 705 and blade box 710 can vary. Upper attachment and lower attachment can be the same, thereby allowing the user to select the desired orientation relative to handle 705.

The upper jaw 714 and lower jaw 716 shown in Figure 21B are completely separate components that are not coupled to one another except for their attachment to the protrusion 707 on the handle 705. The upper jaw 714 and lower jaw 716 may also be hingedly coupled to one another.

The blade cartridge 710 also need not be removable from the handle 705, although it is preferred to remove the blade cartridge 710 from the handle 705 so that the blade cartridge 710 can be discarded after a single use and the handle 705 can be reused for another blade cartridge 710 after resterilization. The handle 705 can be made of a material configured to be resterilized, such as metal or plastic. One or more components of the blade cartridge 710 (e.g., the lower jaw 714 having the bearing surface 715) can be made of a material that is not configured to be resterilized and is therefore disposable, such as plastic.

FIG. 22A shows the blades 712 of the upper jaw 714 relative to the bearing surface 715 of the lower jaw 716. The blades 712 are spaced apart from each other in a precise manner so as to cut the piece of material 101 at two locations in a single cutting actuation of the handle 705. In some embodiments, the blades 712 are spaced apart parallel to each other. In a preferred embodiment and as best shown in FIGS. 22B-22C , the blades 712 are mounted at an angle to each other that accommodates the angle of the bevel, thereby ensuring that the interior space between the blades 712 (at least the portion of the blades 712 that penetrates tissue) is parallel and straight.

FIG. 22B is a detailed view of the blade 712, showing the angled mounting, and FIG. 22C is a detailed view of the blade of FIG. 22B taken at circle C. Each blade 712 includes a sharp distal cutting edge 720 formed by at least one distal bevel. The two blades 712 are mounted at an angle relative to each other so that the inner faces are not parallel and the distal bevels are parallel to each other. As described in more detail below, although the inner faces of the blades 712 themselves are not parallel, the distal bevels of the blades 712 are parallel to each other and are substantially orthogonal to the planar surface of the load-bearing surface 715, and therefore orthogonal to the tissue piece being cut.

At least the inner face or both the inner face and the outer face of each blade 712 may be beveled to form a distal cutting edge 720. The inner face 722 of the blade 712 may be ground to obtain a first cutting surface 724 having a first cutting angle A1. The outer face 723 of the blade 712 may be ground to obtain a second cutting surface 725 having a second cutting angle A2. The first cutting angle A1 may be less than the second cutting angle A2. When the inner faces 722 of the blades 712a, 712b are positioned at an angle φ relative to each other (e.g., using a spacer 726), the cutting angle A1 of the first cutting surface 724 allows the first cutting surface 724 of the first blade 712a to be arranged parallel to the first cutting surface 724 of the second blade 712b (as shown in FIG. 22B ). In other words, the non-parallel angle φ of the blades 712a, 712b relative to each other ensures that the cutting surfaces 724 of the inner faces 722 of the blades 712a, 712b are parallel to each other and also arranged orthogonal to the bearing surface 715, and therefore to the cut tissue resting against the bearing surface 715. The spacer 726 can place the position and distance of the blade(s) 712 within very tight tolerances (e.g., +/- 0.1 mm) to not only help obtain a very consistent and very straight stent 105 from the piece of material 101, but also help load the cut stent into a cannula for delivery, as described elsewhere herein.

The angle of the blade makes the bevels parallel to each other and orthogonal to the load-bearing surface 715, which prevents the piece 101 of the material on the load-bearing surface 715 from being "squeezed out" inward during cutting. Eliminating "squeezing out" can make the piece cut out a more consistent cross-section and improve cutting performance. The blade can cut more tissues of different thicknesses, and when the blade penetrates the tissue, the damage to the tissue itself is less. Although the blade shown has a double-bevel cutting edge (see Figure 22E), the blade box can also include a single-bevel blade (see Figure 22D) that is parallel to each other and installed flatly. If the beveled faces face each other at a certain angle, the resulting internal space between the blades has a completely parallel and straight face.

23A-23C illustrate an embodiment of an ejector spring 730 that can be positioned between blades 712 of a blade cartridge 710. The ejector spring 730 helps eject the cut stent 105 from between the blades 712 after the cutting action is completed, so that the user can grab the cut stent 105 (e.g., with forceps) to proceed to the next step of the procedure (e.g., loading the cut stent 105 into a delivery device). FIG. 23A is a perspective view of a blade 712. FIG. 23B is a perspective view of a blade 712 that is transparent to show the position of the spring 730 relative to the blade 712 and the spacer 726. FIG. 23C is a front end view of the blade 712 showing the spring 730. The ejector spring 730 (e.g., a coil spring, foam, leaf spring, or other spring mechanism) can be coupled to the spacer 726 positioned between the blades 712. The spring 730 acts to move the cut stent 105 out from between the blades 712. The spring 730 in spring structure protrudes between the farthest ends of the blades (see Figure 23 C). This pushes any tissue between the blades 712 downwards so that when the blade box 710 is opened by the unfolding handle 705, the tissue is pushed to the bearing surface 715 of the lower jaw 716, rather than between the blades 712 in the upper jaw 714. The spring 720 has enough flexibility to be compressed upwards between the blades 712 during the cutting motion towards the bearing surface 715, without affecting the cutting motion of the trephine device 700. The support 105 of cutting can then be loaded into the transmission cannula to be implanted in the eye. The ejection spring 730 can be incorporated in any embodiment of the cutter described herein, including the cutting device 300 shown in Figures 18A-18H, to ensure that the support of cutting remains available for user grasping.

The relative arrangement of the various components of the cutting assembly with respect to the cutting device may vary. The arrangement described above with reference to the blade being "above" the tile may be implemented just as easily with the blade being "below" the tile. The directional language used herein is for purposes of clarity and understanding and is not intended to limit the device to a particular arrangement.

19A-19B illustrate an embodiment of a loading device 600. The loading device 600 may include a base 602 having a distal portion 605 including a distal opening or receptacle 606 sized and shaped to receive at least a portion of a tissue cassette (e.g., a nose cone assembly 274). The proximal region of the nose cone assembly 274 may be keyed relative to the receptacle 606 so that it can only be inserted into the receptacle 606 in a single orientation, similar to the keyed connection between the nose cone assembly 274 and the delivery device housing 405. For example, the protrusion 290 at the proximal end of the nose cone assembly 274 may be inserted into at least a portion of the receptacle 606 to align the lumen 238 of the distal shaft 210 with the pusher 620 of the loading device 600. When the handle 643 is in a first configuration relative to the base 602, e.g., lifted upward away from the base 602 as shown in FIG19A , the protrusion 290 of the nose cone assembly 274 can be inserted into the receptacle 606 of the loading device 600. The handle 643 can be pushed into a second configuration, e.g., rotated toward the base 602, to secure the nose cone assembly 274 relative to the loading device 600 (see FIG19B ). The receptacle 606 can clamp at least one area of the nose cone assembly 274 to secure it relative to the loading device 600.

The loading device 600 can receive the cut stent 105 from the cutting device 300 on a portion of the device 600 relative to a movable plow 622. The device 600 can incorporate a recess or loading mark 621 to provide guidance to the user regarding the location of the cut stent 105 relative to the plow 622. The plow 622 can be moved forward along the base 602 and relative to the stent 105 positioned at the mark 621 to cause the stent 105 to align with the lumen 238 of the distal shaft 210. Figures 20A-20B are cross-sectional schematic diagrams showing the bidirectional movement of the plow 622 relative to the base 602 to align the cut stent 105 with the lumen of the shaft 210. Figure 20A shows the plow 622 in a retracted configuration so that the loading mark 621 is located in front of the front surface 624 of the plow 622. The cut stent 105 can be positioned at the loading mark 621 in front of the front surface 624 of the plow 622. The movement of the plow 622 in the direction of arrow A pushes the cut stent 105 toward the terminal region 623 of the base 602. The front surface 624 of the plow 622 and the terminal region 623 of the base 602 form a space coaxial with the lumen of the shaft (not visible in Figures 20A-20B) and substantially matching in size. The front surface 624 of the plow 622 can be curved to form at least a portion of a circle. The terminal region 623 opposite the front surface 624 of the plow 622 can have a curvature that is a mirror image of the curvature of the front surface 624, so that when the plow 622 is placed near the terminal region 623, a tubular structure 625 (see Figure 20B) containing the cut stent 105 is formed. The tubular structure 625 formed when the plow 622 is pushed into contact with the terminal region 623 of the base 602 can have an inner diameter substantially the same as the inner diameter of the distal shaft. As discussed elsewhere herein, the size of the cut stent 105 can be slightly oversized relative to the lumen of the shaft so that the cut stent 105 is compressed or compacted within the shaft. Similarly, when the plow 622 is placed in contact with the terminal region 623 of the base 602, the tubular structure 625 can compress or compact the cut stent 105. The relative curvature of the front surface 624 of the plow 622 and the terminal region 623 of the base 602 can vary, but when one is matched with the other, a complete shape without gaps is formed so that the stent 105 is completely contained within the tubular structure 625. The curvature of the front surface 624 can be at least about 90 degrees of a circle up to about 170 degrees of a circle. The terminal region 623 of the base 602 can have a curvature of at least about 190 degrees of a circle up to about 270 degrees, so that the cut stent 105 is closed to 360 degrees with the front surface 624. Any of a variety of curvatures are contemplated herein such that the cut stent 105 can be pushed forward from the marking 621 toward the terminal region 632 so that it is coaxially aligned with the longitudinal axis of the shaft 210. The surface 624 can form a tubular structure 625 with the terminal region 623 having a cross-section that is not circular (including an elliptical or other curved shape).

Once the cut stent 105 is compressed within the tubular structure 625 and aligned with the lumen of the distal shaft, the pusher 620 of the loading device 600 can be used to compress, compact or otherwise manipulate the cut stent 105 into the lumen of the shaft. The plow 622 can be manipulated in a first direction relative to the base 602, such as by using an actuator operatively coupled to the plow 622. The pusher 620 can be manipulated in a second direction relative to the base 602, such as by using an actuator operatively coupled to the pusher 620. Any of a variety of actuators are contemplated here to move the plow 622 and/or the pusher 620, including a dial, a button, a slider or other actuators. The plow 622 can be moved transversely along an axis A' at a 90 degree angle relative to the longitudinal axis A of the shaft 210. The pusher 620 can move longitudinally or along the longitudinal axis A of the shaft 210. The plow 622 aligns the cut stent 105 with the long axis A of the lumen 238 of the shaft 210, and the pusher 620 loads the cut stent 105 into the lumen 238 of the shaft 210. The pusher 620 is configured to pass through the tubular structure 625 so that the cut stent 105 moves along the longitudinal axis A into the lumen 238. Once the cut stent 105 is loaded into the nose cone assembly 274, the nose cone assembly 274 can be removed from its attachment to the loading device 600 and coupled to the delivery device 400, as described elsewhere herein.

The cutting device 300 and the loading device 600 can be configured to be coupled to or engage with each other so that they form a single system component configured to work in coordination with each other. For example, the cutting device 300 can be coupled to the base 602 of the loading device 600. The base 602 of the loading device 600 can include a handle configured to actuate the cutting assembly 500 of the cutting device 300. In this configuration, the cutting device 300 does not need to be combined with its own handle 343 configured to actuate the cutting assembly 500. Similarly, the pad 515 can be formed by at least a portion of the loading device 600 so that the features of the cutting assembly 500 and the loading device 600 work in coordination with each other to produce a support. The fixing of the tissue, the cutting of the tissue, the transfer of the cut support, and the loading of the cut support into the tissue cassette can all be combined into a single system or can be divided into different devices.

The cut stent 105 loaded and compressed for delivery can be positioned within at least a portion of the cartridge 200, such as within the lumen 238 of the shaft 210. At least a portion of the cartridge 200 can be removed from the cutting device 330 (or loading device 600) and engaged with the delivery device 400 for deployment of the stent 105 from the cartridge 200 into the eye. The compression and transfer of the cut stent 105 described above with respect to the cutting assembly 500 prepares the cut stent 105 for delivery without removing the cut stent 105 from the cartridge 200.

Box 200 can be connected with cutting device 300 having cutting assembly 500 for cutting piece 101 of material and loading assembly for loading the cut support into box 200. Box 200 can then be removed from engagement with cutting device 300 so that it can be connected to conveyor 400. Cutting device 300 does not need to be combined with loading assembly or connected to box 200. For example, the cut support 105 can be manually transferred from cutting device 300 to separate loading device 600, which is connected with box 200 to load the cut support 105 into box 200 as described above. This relationship can include removing and reengaging the entire box 200 or only a portion of the box 200, such as only nose cone assembly 274 (e.g., nose cone 275 and shaft 210). These two arrangements are considered here. Nose cone assembly 274 can be referred to as box 200 in this article. Where the cartridge 200 is described as being removed from engagement with one device to engagement with another device, the description relates to either only the nose cone assembly 274 being removed or the entire cartridge 200 being removed. Where the cartridge 200 is described as being configured to engage with a delivery device 400, the description relates to either only the nose cone assembly 274 being engaged to the delivery device 400 or the entire cartridge 200 being engaged to the delivery device 400. The various instances of coupling between the cartridge 200 and another component of the system 100 may be the entire cartridge 200 or just a portion of the cartridge 200, such as the nose cone assembly 274.

The piece 101 of material can be placed in a portion of the box 200 for cutting, or the piece 101 of material can be placed in a portion of the cutting device 300 to be cut by the cutting assembly 500 and the cut bracket 105 is transferred to the box 200 (or only a portion of the box 200, such as the nose cone assembly 274). The cut bracket 105 can be transferred to the box 200 using the cutting assembly 500 or a component of the cutting device 300, and then the box 200 is separated from the cutting device to be connected to the conveying device. The piece 101 of material can be placed in the area of the cutting assembly 500 for cutting, and then the cut bracket 105 is manually transferred from the cutting assembly 500 to be compacted in the conveying shaft 210, for example, using a loading device 600 separated from the cutting device 300. The cut bracket 105 can be transferred from the cutting assembly 500 using a separate device, including manually. In one embodiment, the system includes a cutting device 300 having a cutting assembly 500. The cut stent 105 from the cutting assembly 500 can be manually transferred (e.g., by pliers) to a transfer device having a compression tool 517 to compress the cut stent 105 into the distal shaft 210. The distal shaft 210 in which the cut stent 105 is compressed can then be connected to the conveying device 400 to deploy the cut stent 105 into the eye. The system can have separate cutting, transfer and conveying devices, rather than one or more integrated devices. The cutting assembly 500 shown in Figures 14A-14H can be a part of the cutting device. The transfer component can be integrated with the cutting device 300, or it can be a separate transfer device, such as the loading device of Figures 19A-19B.

The system 100 may include a conveyor 400 configured to couple with at least a portion of the cartridge 200 holding the cut stents 105. In some embodiments, the entire cartridge 200 having the cut stents 105 is removed from the cutting device 300 and engaged with the conveyor 400 (see FIG. 2 ). In interrelated embodiments, a portion of the cartridge 200 having the cut stents 105 positioned therein is removed from the cutting device 300 and engaged with the conveyor 400 (see FIGS. 6 , 9A-9D ).

In the embodiment shown in Figures 5A-5B, the box 200 holding the cut stent 105 can be removed and loaded into the delivery device 400. Figures 5C-5F show the loading of the tissue box 200 in the delivery device 400 and the deployment of the cut stent 105 using the delivery device 400. The delivery device 400 can be used with the box 200 to deliver the stent 105 to the location of implantation, such as through the intra-path delivery channel. This allows the loading of the stent and the deployment of the stent without having to remove the cut stent 105 from its position in the box 200 in order to load the cut stent 105 into the delivery device 400. At least a portion of the box 200 (e.g., the proximal portion 207 of the box 200 or the area of the nose cone assembly 274) can be held by the delivery device 400 and the distal portion 205 of the box 200 can be inserted into the eye.

The delivery device 400 can include a proximal housing 405 that is sized and shaped to be grasped by a single hand of a user and a distal region 410 that defines an attachment mechanism 425, such as a receptacle 412 that is sized to engage at least a portion of the cartridge 200. In one embodiment, the receptacle 412 can be sized to receive at least a length of the proximal portion 207 of the cartridge 200 (see FIG. 5C and also see FIGS. 17A-17D ).

In an interrelated embodiment, the attachment mechanism 425 can be combined with another male-to-female attachment mechanism, such as a bayonet connector 413 (see Figures 10A-10C, 17A-17C). Figures 17B-17C show a proximal coupler 413a protruding from a proximal region of the nose cone 275 and a corresponding distal coupler 413b protruding from a distal region of the housing 405. The proximal coupler 413a can have a protrusion 290 having a shape corresponding to the shape of the receptacle 292 on the distal coupler 413b, thereby forming a keyed interface. The protrusion 290 of the proximal coupler 413a can be inserted into the receptacle 292 on the distal coupler 413b in a first orientation. The nose cone assembly 274 can then be rotated about the axis in a first direction to secure the nose cone assembly 274 relative to the housing 405 (see the arrow in Figure 10B). To disengage the nose cone assembly 274 from the housing 405, the reverse operation is performed. The shapes of the receptacle 292 and the protrusion 290 can be selected so that rotation of the protrusion 290 relative to the receptacle 292 causes the protrusion 290 to be prevented from being withdrawn from the receptacle 292. The rotation can be about 90 degrees to about 180 degrees to ensure fixation between the nose cone assembly 174 and the housing 405. The shape is shown as an oval in FIG. 10A, but the shape can vary, including rectangular or other geometric shapes and free-form shapes. The shapes of the protrusion 290 and the receptacle 292 can be selected so that they are only coupled together in a single orientation. FIG. 17A shows that the receptacle 292 can be an elongated shape from top to bottom and is combined with an upper area 293 that is smaller in size than the lower area 295 of the receptacle 292. The protrusion 290 can have a corresponding shape that can only be inserted into the receptacle 292 when the smaller upper area of the receptacle 292 is located at the top and the larger lower area is located at the bottom. When inserted into the receptacle 292 , the protrusion 290 may be rotated in a clockwise direction relative to the receptacle 292 , for example 90 degrees, to secure the nose cone assembly 174 relative to the housing 405 .

As mentioned above with respect to the cutting device 300, the attachment mechanism 425 can be keyed so that the box 200 with the cover 214 in place on the base 224 can be received in the attachment mechanism 425 or otherwise engage the attachment mechanism 425 in a single orientation. When the box 200 is coupled to the attachment mechanism 425 of the housing 405, the shaft 210 of the box 200 extends outward from the housing 405 in the distal direction. The keying feature of the attachment mechanism 425 can prevent attachment in the wrong orientation. The attachment mechanism 425 can also provide a secure connection with tactile feedback to the user to indicate when the connection is fully engaged. The size of the attachment mechanism 425 is also designed to ensure that the lumen 238 of the shaft 210 is aligned with the internal mechanism (e.g., push rod 420) of the delivery device 400.

The attachment mechanism 425 of Fig. 5A-5C can be a receptacle 412, and its depth is enough to accommodate the length of the proximal part 207 of box 200, while the shaft 210 remains on the outside of the receptacle 412. The flexible hook 422 can extend into at least a portion of the receptacle 412 (see Fig. 5C). The distal end 424 of the hook 422 can be received in the correspondingly shaped pawl 272 near the proximal region of the tissue cassette 200. Along with the box 200 sliding in the receptacle 412, the distal end 424 of the hook 422 can slide through the proximal end 207 of the box 200 and insert in the pawl 272. The flexibility of the hook 422 allows the hook 422 to be pushed upward when the distal end 424 of the hook 422 advances through the first region of the box 200, and bends back downward when the distal end 424 further advances, thereby engaging the pawl 272 (see Fig. 5D). The spring loaded hook 422 engaging the detent 272 may provide a tactile and/or audible "click" to notify the user that the cartridge 200 has been fully installed within the transport 400, is retained and is ready for transport of the rack 105.

One or more actuators 415 can be positioned on an area of the housing 405. The actuators 415 can also be manipulated by a single hand of a user, such as with a thumb or finger. The configuration of the actuators 415 can vary. For example, the actuators 415 can include any of a variety of knobs, buttons, sliders, dials, or other types of actuators configured to move one or more components of the conveyor 400 (as described in more detail below).

The delivery device 400 may include a push rod 420 configured to be moved by one or more actuators 415. Once the desired position is reached with the distal end of the shaft 210, the push rod 420 (also referred to herein as a pusher or a pressing tool) may be used with the cartridge 200 to deliver the stent 105 from the cartridge 200. The size and shape of the push rod 420 may be complementary to the interior dimensions of the shaft 210. For example, in the case where the shaft 210 of the cartridge 200 has a rectangular cross-sectional shape, the cross-section of the push rod 420 may be rectangular. This allows the push rod 420 to effectively push the cut stent 105 through the lumen 238 of the shaft 210.

Prior to coupling the tissue cassette 200 to the transport device 400, the push rod 420 can be fully retracted in a proximal position so that the push rod 420 does not interfere with the loading of the cassette 200. Once the cassette 200 is installed and held in the transport device 400, as shown in FIGS. 5D and 9B, the push rod 420 can be advanced distally through the proximal port in the cassette 200 and into the lumen 238 of the shaft 210 (see FIGS. 5E and 9C). In some embodiments, the push rod 420 can be advanced through the lumen 238 and out of the distal opening 230 of the lumen 238 to deploy the stent 105. In other embodiments, the push rod 420 is advanced to a distal position near the proximal end of the stent 105 in the lumen 238, and the shaft 210 is withdrawn proximally while the push rod 420 remains stationary to deploy the stent 105 (see FIGS. 5F and 9D).

The shaft 210 can be withdrawn proximally by movement of the cartridge 200 relative to the delivery device 400 in the proximal direction while the push rod 420 remains stationary, so as to deploy the stent 105 in the eye (see FIGS. 5F and 9D ). Thus, the push rod 420 can act as a stopper, thereby preventing the stent 105 from following the shaft 210 as it is retracted. The result is that the stent 105 is dislodged from the shaft 210 and remains in the tissue. In other embodiments, both the cartridge 200 and the push rod 420 can be moved to enable the stent to be deployed from the shaft 210. In some embodiments, the push rod 420 can be advanced relative to the shaft 210 to fully deploy the stent 105 from the lumen.

In some embodiments, the push rod 420 can be coupled to the first actuator 415 and the cartridge 200 can be coupled to the second actuator 415. The first and second actuators 415 can be sliders, buttons, or other configurations or combinations of actuators configured to advance and retract their respective components. The first actuator 415 coupled to the push rod 420 can be withdrawn proximally so that the push rod 420 is in its most proximal position when the cartridge 200 is engaged by the attachment mechanism 425 of the delivery device 400. The user can advance the first actuator 415 to push the push rod 420 distally to advance the stent 105 within the lumen 238 of the cartridge 200 toward the distal opening 230 of the shaft 210. After the cut stent 105 is ready to enter its distal position within the lumen 238, the shaft 210 of the cartridge 200 can be used to dissect tissue of the eye until the target location is reached. Once the shaft 210 is in position to deploy the stent 105 in the eye, the first actuator 415 coupled to the push rod 420 can be maintained in the distal position, and the second actuator 415 is actuated (e.g., withdrawing 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 push rod 420 deploys the stent 105 from the lumen 238 to the anatomical structure. The stent 105 can be deployed from the lumen 238 by advancing the push rod 420 so that the stent 105 is fully exposed from the lumen 238.

Fig. 5E shows the box 200, which is mounted in the receptacle 412 of the conveyor 400 so that there is a space between the end of the receptacle 412 and the nearest end of the box 200. The depth of the space defines the maximum distance 200 that the box can be retracted. The support 105 is located near the distal opening 230 relative to the inner cavity 238, and the push rod 420 is advanced to its distal position so that the distal end of the push rod 420 abuts against the proximal end of the support 105. The distal end 424 of the hook 422 is retained in the pawl 272 and the second actuator 415 has not yet been actuated. The proximal end 426 of the hook 422 is connected to the spring 430. When the second actuator 415 is in a stationary state before actuation, the hook 422 is pushed distally into the first configuration. When 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 downward), the spring 430 is released and pushes the proximal end 426 of the hook 422 toward the proximal end of the housing 405. The hook 422 moves proximally and drags the box 200 with it - which is coupled to the hook 422 due to the engagement of the distal end 424 of the hook 422 in the pawl 272. The distance that the hook 422 moves proximally thus retracts the box 200 deeper into the receptacle 412. The push rod 420 can remain stationary during the retraction of the box 200. The relative movement 420 between the shaft 210 and the push rod 420 deploys the stent 105 from the inner cavity 238 (see Figure 5F).

It should be understood that additional distal movement of the push rod 420 can be used to assist in deploying the stent 105 from the lumen 238. It should also be understood that the push rod 420 advancement and the cartridge 200 retraction can be controlled by a dual actuator 415 as described above or by a single actuator 415 capable of achieving movement of both the push rod and the cartridge 200 depending on the degree of actuation. In addition, during the process of using the push rod 420 as a plunger, the shaft 210 can be used to inject a viscous material, such as a viscoelastic material. The implantation and delivery methods of the stent 105 are described in more detail below.

11A-11C illustrate the steps of deploying a stent by using a first actuator 415a (which in this case may be a slider) of the 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 nose cone assembly 274 (or the entire box 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 cut stent 105 through the lumen 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 removable guard 432 that is arranged to prevent a user from inadvertently pushing the slider past the second ready position. The guard 432 may be pushed downward toward the housing 405 of the delivery device so that the second actuator 415b is covered by the guard 432, thereby preventing the second actuator 415b from being accidentally activated. The guard 432 has a certain length so that the guard 432 extends over at least a portion of the slider track 435 (or has a feature 433 extending within at least a portion of the slider track 435), thereby preventing the first actuator 415a from moving further distally in addition to blocking the second actuator 415b (Figure 11B). Once the bracket 105 is advanced to the ready position and is ready to be deployed in the eye, the guard 432 can be rotated upward to expose the second actuator 415b out of the way and remove the feature 433 from the track 435. The first actuator 415a is free to slide further distally along the track 435, and the second actuator 415b can be depressed (Figure 11C). The guard 432 can also be completely removed from the device 400, or the device 400 does not include any guard 432. The housing of the device 400 can include one or more markings 434, which are intended to provide feedback to the user regarding the position of the push rod 420 through the shaft 210. As described elsewhere herein, advancing the push rod 420 to one or more positions relative to the housing may also provide tactile feedback to the user.

12A-12D show in cross-section the delivery device 400 before and after the push rod 420 is advanced to the second position. Once the nose cone assembly 274 is attached to the delivery device 400, the first actuator 415 and the push rod 420 can be advanced from the initially retracted first position to the second position. The first actuator 415a and the push rod 420 can be advanced to the second position, resulting in the push rod 420 being inserted into the lumen 238 behind the material to be delivered (e.g., the cut stent 105). The guard 432 having a protruding feature 433 on its underside can prevent the first actuator 415a from sliding past the second position. The positioning of the second position is designed to place the leading face of the push rod 420 at a predetermined distance (e.g., 6 mm) from the distal end of the shaft 210. Once the user has created the desired rupture and is ready to transfer material from the lumen, the push rod 420 can be advanced to its third, forward position (with the guard 432 not blocking, or otherwise removed or absent from the device 400). The second actuator 415b can be engaged to release the material from the shaft 210. The second actuator 415b, as described elsewhere herein, can retract the shaft 210 while the push rod 420 remains stationary, ultimately releasing the stent 105 from the lumen. The nose cone assembly 274 is withdrawn while the push rod 420 remains stationary. The push rod 420 can also be advanced to deploy the stent 105 from the lumen 238. The stent 105 can be deployed from the lumen 238 so that at least a portion of the stent 105 is positioned between tissue layers, such as within the supraciliary cavity between ciliary tissue and scleral tissue, or within Schlemm's canal. The support 105 can be deployed so that it is positioned in the ciliary superior chamber so that at least the distal region is positioned between the ciliary tissue and the sclera, and the proximal end is positioned in the ciliary superior fissure. When positioned in the ciliary superior fissure, the proximal end does not need to extend into the anterior chamber. Preferably, the proximal end of the support 105 is positioned so that it remains flush with the cleft between the ciliary tissue and the sclera tissue and does not extend into the anterior chamber. The existence of one or more fenestrations 276 in the shaft 210 and/or the substantially transparent or translucent outer tube member 278 forming the distal region 212 of the shaft 210 can assist the support 105 to be positioned flush with the cleft by helping to visually inspect the implant in the lumen 238 and the lumen 238 when the support 105 is pushed through the lumen 238 distally.

A mechanical backstop 450 can be used to assist in maintaining a fixed position of the push rod 420 during the deployment of the stent 105. The backstop 450 can prevent the push rod 420 from being pushed proximally by the stent 105 within the lumen 238 of the shaft 210. The backstop 450 can be located within the housing 405, below the slider track 435 in the housing 405, and the actuator 415a slides through the slider track 435. The size and shape of the backstop 450 are designed to engage with a corresponding area of the actuator 415a located within the housing 405. The outer portion of the actuator 415a extends to the outside of the slider track 435 of the housing 405 and is configured for the user to engage the actuator 415a. The inner portion of the actuator 415a is located within the housing 405 and is connected to the proximal region 444 of the push rod 420. The advancement of the actuator 415a along the slider track 435 pushes the push rod 420 distally relative to the housing 405, so that the distal end of the push rod 420 is pushed toward the opening of the shaft 210. The internal portion of the actuator 415a located within the housing 405 may also include a flexure 452 having a protrusion 451 extending upward toward the slider track 435. The flexure 452 can move between a compressed position and a relaxed configuration. When the actuator 415a is in a fully withdrawn position and slides to the proximal end of the slider track 435, the flexure 452 is pushed downwardly by the inner surface of the housing 405 to the compressed position. When the actuator 415a slides distally along the slider track 435, the protrusion 451 also slides along the interior of the housing 405 until it reaches the backstop 450. When the position of the backstop 450 is reached, the flexure 452 relaxes upward to the relaxed configuration. The protrusion 451 on the upper surface of the flexure 452 contacts the upper end of the housing 405, and the proximal surface of the protrusion 451 engages with the distally facing surface of the stop 450. The engagement between the surfaces of the stop 450 and the protrusion 451 prevents any unintended proximal movement of the actuator 415a, thereby preventing proximal movement of the push rod 420 that may occur during the deployment of the stent 105 from the shaft 210.

Figures 17G-17H show that the outer portion of the actuator 415a outside the housing 405 abuts against the feature 433 on the button guard 432 protruding in the slider track 435. The projection 451 engages against the stop 450. When the actuator 415a reaches this position, the bracket 105 has been advanced to the ready position in the shaft 210 and is ready to be deployed in the eye. The button guard 432 can be rotated upward to remove, revealing the second actuator 415b. Pressing the second actuator 415b causes the bracket 105 to be deployed from the shaft 210, for example, by retracting the shaft 210 while the push rod 420 remains fixed in the ready position. The stop 450 prevents the push rod 420 from moving proximally with the shaft 210. If necessary, the user can retract the actuator 415a by lifting the front end area of the actuator 415a so that the rear end with the projection 451 is deflected downward due to the flexibility of the flexure 452 (see Figure 17I). Downward movement of the rear end of the actuator 415a disengages the protrusion 451 from the backstop 450, thereby allowing the actuator 415a to move proximally along the slide track 435, for example, to reset the instrument for further use.

The delivery device 400 and the cartridge 200 (or nose cone assembly 274) can be a single-use device incorporating a lock-out after the stent 105 is deployed, or can be sterilized and reused. The resetting of the actuator 415a described above allows the housing 405 to be reused after the stent 105 is deployed. Figures 13A-13B show an additional resetting mechanism 436, so that the deployment structure can be reset and the delivery device 400 can be reused. Activating the resetting mechanism 436, such as sliding a button forward, can return the deployment structure to the standby position. The resetting mechanism 436 can also be performed by pulling the nose cone assembly 274 or the bayonet connector 413 of the delivery device 400 distally until the second actuator 415 returns to its initial standby position. If desired, the nose cone assembly 274 can be removed from the delivery device 400 and additional material can be loaded into the shaft 210 as described elsewhere herein. The delivery device 400 can be provided in an actuated or non-standby state, and the user equips the device when in use. Delivery device 400 may also be a single-use device that cannot be reset after deployment, such as by lacking reset mechanism 436 .

A nose cone assembly transferable between a conveyor and a cutting device can be mounted relative to a main assembly of the cutting device. A tissue piece can be cut by the cutting device and loaded into the nose cone assembly, and the nose cone assembly can be transferred from the main assembly of the cutting device back to be connected to the conveyor for deployment in a patient. The configuration of the nose cone assembly can vary, including any transferable box described herein. In one embodiment, the nose cone assembly can be mounted relative to the cutting assembly by connecting the proximal end of the nose cone to the base so that the longitudinal axis of the lumen of the shaft extending distally from the nose cone is aligned with the longitudinal axis of the corresponding catheter drawn from the slot. The tissue piece can be placed in the loading area region of the base relative to a movable stopper plate on the main assembly. Both the loading area region and the movable stopper 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 slide forward into the cutting area until the piece abuts the stopper plate. Once positioned against the stopper plate, the tissue piece is positioned at a specified width by the cutter. Therefore, the stopper plate provides a calibrated stop point for the tissue piece before cutting. The element designed to fix the tissue piece in this position can be activated, such as lowered above the tissue piece to keep the tissue in place, and optionally compress the tissue to a specific height before cutting. Once the retaining plate is lowered onto the piece to keep it in place, the cutting rod can be lowered to cut the tissue piece with one or more blades. The stopper plate and the retaining plate can be removed from the cut support, and the rest of the tissue piece is removed from the assembly. The cut support can be loaded using a tissue loader slider. The tissue loader slider can push the cut support into a position relative to the longitudinal axis of the shaft in the nose cone assembly. For example, the tissue loader slider can be placed in place and slid forward as much as possible until the slider abuts against the boss on the main assembly, indicating that the cut support has been fully transferred into the compression channel and is ready to be pushed into the shaft of the nose cone assembly. An elongated tool such as a tissue pusher rod can be inserted into the main assembly along the longitudinal axis to push the cut support from the main assembly into the shaft of the nose cone assembly. The rod can be designed to push the tissue slider toward the end of the nose cone assembly without completely pushing the cut support out of the inner cavity of the shaft. The nose cone assembly can then be disconnected from the main assembly and attached to a delivery device for deployment into a patient.

In other embodiments, the box 200 itself holds the tissue piece for cutting. For example, Fig. 3 A shows that the cover 214 of the box 200 can be removed from the slot 214 in the base 224, thereby revealing the recess 221. The piece 101 of the material can be manually loaded in the recess 221. The size of the piece 101 of the material can be set to receive in the recess 221, or it can be trimmed to ensure that its size is suitable for receiving in the recess 221. The cover 214 of the box 200 is repositioned on the base 224 and pushed through the slot 215 until the lower part 222 of the cover 214 engages the piece 101 of the material to capture it against the projection 271. When in the closed configuration, the cover 214 can compress and/or tension the piece 101 of the material in the box 200. Fig. 2 shows that the loaded tissue box 200 can be installed in the receptacle 306 of the cutting device 300, wherein the handle 343 is 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 101 of material until the blade 344 of the cutting member 312 completely cuts through the piece 101 of material (FIG. 4B). When the blade 344 is still in the fully cut position relative to the box 200, the pusher 320 of the cutting device 300 can be pushed distally to prepare the shaft 210 and place the now cut stent 105 within the lumen 238 of the shaft 210 from the lumen 238 toward the opening 230 near the distal region 212 of the shaft 210. The pusher 320 can be retracted from the box 200 and the box 200 is removed from the cutting device 300. As described elsewhere herein, removing the box 200 from the cutting device 300 may include removing the entire box 200 from the device 300 or disassembling the nose cone assembly 274 of the box 200, as shown in FIG.

The prepared tissue cassette 200 having the cut stent 105 positioned within the lumen 238 of the shaft 210 can be installed with the delivery device 400 (e.g., inserted into the receptacle 412 or attached via the bayonet connector 413 or other attachment mechanism 425). The push rod 420 of the delivery device 400 is withdrawn in the most proximal position and the cassette 200 is coupled to the delivery device 400. The push rod 420 can be advanced using the first actuator 415 from a first retracted position suitable for loading the cassette 200 to a second prepared position such that the delivery device 400 and the cassette 200 are now ready for use with a patient.

In general, the stent 105 located within the shaft 210 can be implanted through a transparent corneal or scleral incision formed using the shaft 210 or a device separate from the box 200. An observation lens such as a gonioscopic lens can be positioned near the cornea. The observation lens is capable of observing the internal areas of the eye, such as the scleral protrusion and scleral limbus, from a position in front of the eye. The observation lens can optionally include one or more guide channels sized to receive the shaft 210. An endoscope can also be used to assist in visualization during delivery. Ultrasonic guidance can also be used using a high-resolution biomicroscope, OCT, etc. Alternatively, a small endoscope can be inserted through another limbal incision in the eye to image the eye during the implantation process.

The distal end 216 of shaft 210 can penetrate the cornea (or sclera) to enter the anterior chamber. In this regard, a single incision can be made in the eye, for example, in 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 transparent cornea. Shaft 210 can be used to make an incision or a separate cutting device can be used. For example, a knife tip device or a diamond knife can be used initially to enter the cornea. Then a second device with a scraper end can be advanced above the knife tip, wherein the plane of the scraper is positioned to coincide with the dissecting plane. The scraper end device can be shaft 210.

The corneal incision can be of sufficient size to allow the passage of the shaft 210. In one embodiment, the size of the incision is about 1 mm. In another embodiment, the size of the incision is no greater than about 2.85 mm. In another embodiment, the incision is no greater than about 2.85 mm and greater than about 1.5 mm. It has been observed that incisions up to 2.85 mm are self-sealing incisions.

After being inserted through the incision, the shaft 210 can be advanced into the anterior chamber along a pathway that enables the stent 105 to be delivered from the anterior chamber to a target location, such as the supraciliary space or the suprachoroidal space. The shaft 210 can be further advanced into the eye by positioning the shaft for access so that the distal-most tip 216 of the shaft 210 penetrates tissue at the canthus, such as the region of the iris root or ciliary body, or the iris root portion of the ciliary body near its tissue boundary with the scleral process.

The scleral prominence is an anatomical landmark on the wall of the corner of the eye. The scleral prominence is above the level of the iris but below the level of the trabecular meshwork. In some eyes, the scleral prominence may be obscured by the lower band of the pigmented trabecular meshwork and is directly behind it. The axis 210 can travel along a pathway toward the corner of the eye and the scleral prominence so that the axis 210 passes near the scleral prominence on the way to the supraciliary cavity, but it is not necessary to penetrate the scleral prominence during delivery. Instead, the axis 210 can be adjacent to the scleral prominence and move downward to dissect the tissue boundary between the sclera and the ciliary body, with the dissecting entry point starting just below the scleral prominence, near the root of the iris, or the iris root portion of the ciliary body. In another embodiment, the delivery pathway of the implant intersects with the scleral prominence.

Axis 210 can approach the corner of the eye from the same side of the anterior chamber as the deployment position, so that axis 210 does not have to advance through the iris. Alternatively, axis 210 can approach the corner of the eye from passing 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 a variety of pathways. Axis 210 does not necessarily cross the eye and does not intersect with the central axis of the eye. In other words, when looking at the eye along the optical axis, the position where the corneal incision and the bracket 105 are implanted at the corner of the eye can be in the same quadrant. In addition, the path of the bracket 105 from the corneal incision to the corner of the eye should not pass through the center line of the eye to avoid touching the pupil.

The shaft 210 can be continuously advanced into the eye, for example, by about 6 mm. The dissection plane of the shaft 210 can follow the curve of the inner scleral wall, so that the stent 105 mounted in the shaft, for example, after penetrating the iris root or the iris root portion of the ciliary body CB, can bluntly dissect the boundary between the tissue layers of the scleral protrusion and the ciliary body CB, so that the distal region of the stent 105 extends through the supraciliary space and is then further located between the tissue boundaries of the sclera and choroid forming the supraciliary space.

Once properly positioned, stent 105 can be released from shaft 210. In some embodiments, stent 105 can be released by withdrawing shaft 210, while push rod 420 prevents stent 105 from being withdrawn with shaft 210.

Once implanted, the stent 105 forms a fluid communication passage between the anterior chamber and the target passage (e.g., the supraciliary space or the supraciliary space). As described above, the stent 105 is not limited to implantation in the supraciliary space or the supraciliary space. The stent 105 can be implanted in other locations that provide fluid communication between the anterior chamber and a location in the eye, such as Schlemm's canal or a subconjunctival location of the eye. In another embodiment, the stent 105 is implanted to form a fluid communication passage between the anterior chamber and Schlemm's canal and/or a communication passage between the anterior chamber and a subconjunctival location of the eye. It should be understood that the devices described herein can also be used to deliver stents transsclerally and from an intra-pathway route.

As described above, the material used to form the scaffold may be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

The scaffolds described herein can be used to prevent or treat a variety of systemic and ocular diseases, such as inflammation, infection, cancerous growth. More specifically, eye diseases such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, herpes simplex virus and adenovirus infection can be treated or prevented.

The following classes of drugs can be delivered using the device of the present invention: antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport/mobility approximants (e.g., colchicine, vincristine, cytochalasin B, and related compounds); anti-glaucoma drugs, including beta-blockers such as timolol, betaxolol, atenolol, and prostaglandin analogs—bimatoprost, travoprost, latanoprost, etc.; carbonic anhydrase inhibitors, such as acetazolamide, methazolamide, dichlorphenamide, acetazolamide; and neuroprotectants, such as nimodipine and related compounds. Other examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; antibacterials such as sulfonamides, sulfacetamide, sulfadimethoxazole, and sulfisoxazole; antifungals such as fluconazole, nitrofuracil, amphotericin B, ketoconazole, and related compounds; antivirals such as trifluridine, acyclovir, ganciclovir, DDI, AZT, foscamet, adenosine, trifluridine, herpes, ribavirin, protease inhibitors, and anticytomegalovirus agents; antiallergics such as methapyrine; chlorpheniramine; allergens, pyrilamines, and phenpyridines; anti-inflammatory drugs, such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, flumethasone, betamethasone, and triamcinolone; decongestants, such as phenylephrine, naphazoline, and tetrahydrazide; miotics and anticholinesterases, such as pilocarpine, carbachol, diisopropyl fluorophosphate, iodine, and desergotamine bromide; mydriatics, such as atropine sulfate, cyclopentolone, homatropine, scopolamine, tocatropine, and euctropine; sympathomimetics, such as epinephrine and vasoconstrictors and vasodilators; ranibizumab, bevacizumab, and triamcinolone.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, such as AT-100, available from Bayer AG, Leverkusen, Germany) may also be delivered. Ibuprofen, such as from Wyeth, Collegeville, Pennsylvania /> Indomethacin; mefenamic acid), COX-2 inhibitors (Pharmacia, Peapack, NJ /> COX-1 inhibitors), including prodrugs/> Immunosuppressants, such as Sirolimus (from Wyeth, Collegeville, Pennsylvania /> ), or inhibitors of matrix metalloproteinases (MMPs) that act early in the inflammatory response pathway (e.g., tetracycline and tetracycline derivatives). Anticoagulants such as heparin, antifibrinogen, fibrinolysin, anticoagulant activating enzymes, etc. may also be delivered.

Antidiabetic agents that can be delivered using the present device include acethexamide, chlorsulfonylurea, glipizide, glyburide, tolazoamide, tolbutamide, insulin, aldose reductase inhibitors, and the like. Some examples of anticancer agents include 5-fluorouracil, doxorubicin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, estramustine, etoposide, evagonist, filgrastim, floxuridine, fludarabine, fluorouracil, fluoxymesterone, flutamide, goserelin, isosulfonylurea, leuprolide, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, pentostatin, pipobroman, plicamycin, procarbazine, sagamustine, streptozocin, tamoxifen, paclitaxel, teniposide, thioguanine, uracil mustard, vinblastine, vincristine, and vindesine.

Hormones, peptides, nucleic acids, carbohydrates, lipids, glycolipids, glycoproteins and other macromolecules can be delivered using the device. Examples include: endocrine hormones such as pituitary, insulin, insulin-related growth factor, thyroid, growth hormone; heat shock proteins; immune response modifiers, such as muramyl dipeptide, cyclosporin, interferon (including alpha, beta and gamma interferon), interleukin 2, cytokines, FK506 (an epoxy-pyrido-oxazole ring tricosinone, also known as tacrolimus), tumor necrosis factor, pentostatin, thymopentin, transforming factor beta2, erythropoietin; anti-tumor production proteins (e.g., anti-vascular endothelial growth factor, interferon), etc. 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.

In various embodiments, description is made with reference to the accompanying drawings. However, certain embodiments may be implemented without one or more of these specific details, or in combination with other known methods and configurations. In the description, many specific details, such as specific configurations, dimensions, and processes, are described to provide a thorough understanding of the embodiments. In other cases, well-known processes and manufacturing techniques are not particularly described in detail so as not to unnecessarily make the description unclear. References to "one embodiment," "embodiment," "an implementation," "implementation," etc. throughout this specification sheet mean that the specific features, structures, configurations, or characteristics described are included in at least one embodiment or implementation. Therefore, phrases "one embodiment," "embodiment," "an implementation," "implementation," etc. that appear in different places throughout this specification sheet do not necessarily refer to the same embodiment or implementation. In addition, specific features, structures, configurations, or characteristics may be combined in any suitable manner in one or more embodiments.

Relative terms can be used throughout the description to 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 here can be an operator, so that the terms "proximal" and "distal" refer to the operator using the device. The device area closer to the operator can be described as "proximal" in this article, and the device area farther away from the operator can be described as "distal" in this article. Similarly, the terms "proximal" and "distal" can also be used in this article to refer to the patient's anatomical position from the perspective of the operator or from the perspective of the entry point or along the insertion path from the entry point of the system. Therefore, the proximal position may refer to a position in the patient's body closer to the entry point of the device along the insertion path toward the target, and the distal position may refer to a position in the patient's body farther from the entry point of the device along the insertion path toward the target position. However, these terms are provided to establish a relative reference system, rather than to limit the use or orientation of the device to the specific configuration described in various embodiments.

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

Although this specification contains many details, these should not be interpreted as limitations on the scope of what is claimed or may be claimed, but rather as descriptions of specific features of specific embodiments. Certain features described in the context of a single embodiment in this specification may also be implemented in combination in a single embodiment. Instead, 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. In addition, although features may be described above as working in certain combinations and even initially claimed as such, one or more features from the combination may be removed from the claimed combination in some cases, and the claimed combination may be for a sub-combination or a variant of a sub-combination. Similarly, although operations are depicted in a particular order in the accompanying drawings, this should not be understood as requiring these operations to be performed in the particular order shown or in sequence, or requiring all illustrated operations to be performed to obtain the desired result. Only a few examples and implementations are disclosed. The described examples and implementations and other implementations may be varied, modified, and enhanced based on the disclosed content.

In the above description and claims, phrases such as "at least one of ... " or "one or more of ... " may appear after the connected list of elements or features. The term "and/or" may also appear in a list of two or more elements or features. Unless there are other implicit or explicit contradictions with the context in which it is used, such phrases are intended to represent any element or feature listed individually or any combination of quoted elements or features with any other quoted elements or features. For example, the phrases "at least one of A and B", "one or more of A and B" and "A and/or B" are each intended to represent "single A, single B or A and B together". Similar explanations are also intended to be used 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", "A, B and/or C" each mean "single A, single B, single C, A and B together, A and C together, B and C together, or A and B and C together".

The use of the term "based on" in the above and claims is intended to mean "based, at least in part, on" such that non-recited features or elements are also allowed.

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

P Example

P Example 1. A system for preparing an implant and inserting the implant intraocularly into an eye of a patient, the system comprising: a tissue cassette configured to receive and hold a piece of material; a cutting device; and a conveying device.

P Example 2. A system according to P Example 1, wherein the tissue box includes a shaft extending from a distal end of the tissue box, at least the distal region of the shaft is sized and shaped for insertion into the anterior chamber of the eye, wherein the shaft includes an inner cavity.

P Example 3. A system according to P Example 2, wherein the tissue cassette further comprises a base and a cover, the base being configured to receive the piece and the cover being configured to hold the piece fixed against the base.

P Example 4. A system according to P Example 3, wherein the cutting device includes a cutting member configured to cut a piece of material positioned within the tissue box.

P Example 5. A system according to P Example 4, wherein a piece of material is cut with a cutting member to form an implant from the piece, the implant being configured to be implanted in an eye of a patient.

P Example 6. A system according to P Example 5, wherein the delivery device includes an actuator configured to deploy the implant positioned within the cartridge through the lumen of the shaft into the eye.

P Example 7. A method for preparing an implant for implantation in a patient's eye and inserting the implant into the patient's eye, the method comprising: inserting a piece of material into a tissue box, the tissue box comprising a shaft extending from the distal end of the tissue box, at least the size and shape of the distal region of the shaft being designed to be inserted into the anterior chamber of the eye, wherein the shaft includes an inner cavity; connecting the tissue box to a cutting device, the cutting device having a cutting member, the cutting member being configured to cut the piece of material within the tissue box; while the tissue box is connected to the cutting device, cutting the piece with the cutting member to form an implant from the piece; separating the tissue box from the cutting device; connecting the tissue box to a conveying device; inserting the distal region of the shaft into the anterior chamber of the eye; positioning the distal region near eye tissue; and actuating the conveying device to deploy the implant from the box through at least a portion of the inner cavity so that the implant engages the eye tissue.

P Example 8. The method according to P Example 7 also includes conveying viscous material through the shaft.

P Example 9. A system for preparing an implant and inserting the implant intraocularly into an eye of a patient, the system comprising: a tissue cassette configured to receive and hold a piece of material; and a delivery device.

P Example 10. A system according to P Example 9, wherein the tissue box includes a shaft extending from a distal end of the tissue box, at least the distal region of the shaft is sized and shaped for insertion into the anterior chamber of the eye, wherein the shaft includes an inner cavity.

P Example 11. A system according to P Example 10, wherein the tissue cassette further comprises a base and a cover, the base being configured to receive the piece and the cover being configured to hold the piece fixed against the base.

P Example 12. A system according to P Example 11, further comprising a cutting device, wherein the cutting device comprises a cutting member configured to cut a piece of material positioned within the tissue box.

P Example 13. A system according to P Example 12, wherein the piece of material is cut with a cutting member to form an implant from the piece, the implant being configured to be implanted in the patient's eye.

P Example 14. A system according to P Example 13, wherein the delivery device includes an actuator configured to deploy an implant positioned within at least a portion of the box through the inner cavity of the shaft into the eye.

P Example 15. A system according to P Example 10, wherein the tissue cassette includes a nose cone assembly, the nose cone assembly including the distal region and the shaft of the tissue cassette, wherein the nose cone assembly is reversibly coupled to the tissue cassette and reversibly coupled to the delivery device.

P Example 16. A system according to P Example 10, wherein the shaft of the tissue cassette is configured to convey a viscous material.

P Example 17. A method for preparing an implant for implantation into a patient's eye and inserting the implant into the patient's eye, the method comprising: inserting a piece of material into a tissue box, the tissue box comprising a shaft extending from the distal end of the tissue box, the size and shape of at least the distal region of the shaft being designed for insertion into the anterior chamber of the eye, wherein the shaft includes an inner cavity; connecting the tissue box to a cutting device, the cutting device having a cutting member, the cutting member being configured to cut the piece of material within the tissue box; while the tissue box is connected to the cutting device, cutting the piece with the cutting member to form an implant from the piece; separating at least a portion of the tissue box from the cutting device; connecting at least a portion of the tissue box to a conveying device; inserting the distal region of the shaft into the anterior chamber of the eye; positioning the distal region near eye tissue; and actuating the conveying device to deploy the implant from the box through at least a portion of the inner cavity so that the implant engages eye tissue.

P Example 18. The method according to P Example 17 also includes conveying viscous material through the shaft.

P Example 19. A system for preparing an implant from a piece of material and inserting the implant intraocularly into a patient's eye, the system comprising: a tissue box comprising a nose cone and a distal shaft defining an inner cavity between the nose cone and a distal region of the distal shaft; a cutting device configured to be connected to the nose cone; and a conveying device configured to be connected to the nose cone.

P Example 20. A system according to P Example 19, wherein the size and shape of at least the distal region of the distal shaft are designed for insertion into the anterior chamber of the eye.

P Example 21. A system according to P Example 20, wherein the distal-most tip of the distal shaft is configured to dissect tissue for implantation into the superior ciliary fissure, Schlemm's canal, or transscleral implantation.

P Example 22. A system according to P Example 20, wherein the cutting device includes a base configured to receive the piece.

P Example 23. A system according to P Example 22, wherein the cutting device includes a cutting member configured to cut the piece of material into the implant.

P Example 24. A system according to P Example 23, wherein the cutting device also includes a compression tool configured to push the implant into the inner cavity of the distal shaft.

P Example 25. A system according to P Example 24, wherein the delivery device includes an actuator configured to deploy the implant compressed within the inner cavity of the distal shaft into the eye.

P Example 26. A system according to P Example 25, further comprising a movable inner slender member that is operably connected to the actuator to advance the implant through the inner cavity and out of the distal opening of the distal shaft.

P Example 27. A method for preparing an implant for implantation in a patient's eye from a piece of material and inserting the implant into the patient's eye, the method comprising: connecting a tissue box to a cutting device, the tissue box comprising a shaft extending from a distal end of the tissue box, the size and shape of at least the distal region of the shaft being designed for insertion into the anterior chamber of the eye, wherein the shaft comprises an inner cavity, the cutting device having a cutting member, the cutting member being configured to cut the piece of material; cutting the piece with the cutting member to form an implant from the piece; compressing the implant within the inner cavity of the shaft; separating the tissue box from the cutting device; connecting the tissue box to a conveying device; inserting the distal region of the shaft into the anterior chamber of the eye; positioning the distal region near eye tissue; and actuating the conveying device to deploy the implant from the inner cavity so that the implant engages the eye tissue.

P Example 28. The method according to P Example 27 also includes conveying viscous material through the shaft.

P Example 29. A system for preparing an implant and inserting the implant intraocularly into an eye of a patient, the system comprising: a tissue cassette; and a delivery device.

P Example 30. A system according to P Example 29, wherein the tissue box includes a shaft extending from a distal end of the tissue box, at least the distal region of the shaft is sized and shaped for insertion into the anterior chamber of the eye, wherein the shaft includes an inner cavity.

P Example 31. According to P Example 30, the system also includes a cutting device, wherein the cutting device includes a cutting member configured to cut pieces of material.

P Example 32. A system according to P Example 31, wherein a piece of material is cut with a cutting member to form an implant from the piece, the implant being configured to be implanted in an eye of a patient.

P Example 33. A system according to P Example 32, wherein the delivery device includes an actuator configured to deploy an implant positioned within the shaft through the lumen of the shaft into the eye.

P Example 34. A system according to P Example 30, wherein the tissue cassette includes a nose cone assembly, which includes a distal region and a shaft of the tissue cassette, wherein the nose cone assembly is reversibly coupled to the tissue cassette and reversibly coupled to the delivery device.

P Example 35. A system according to P Example 30, wherein the shaft of the tissue cassette is configured to convey a viscous material.

P Example 36. A method for preparing an implant for implantation in a patient's eye and inserting the implant into the patient's eye, the method comprising: cutting a piece of material with a cutting member of a cutting device to form an implant from the piece; compressing the implant within an inner cavity of an axis extending from a distal end of a tissue box; separating at least a portion of the tissue box from the cutting device; connecting at least a portion of the tissue box to a delivery device; inserting a distal region of the axis into the anterior chamber of the eye; positioning the distal region near eye tissue; and actuating the delivery device to deploy the implant from the tissue box through at least a portion of the inner cavity so that the implant engages the eye tissue.

P Example 37. The method according to P Example 36 also includes conveying viscous material through the shaft.

P Example 38. A method of treating the eye using minimally modified biological tissue.

P Example 39. A method according to P Example 38, wherein the biological tissue is scleral tissue, and minimally modifying the scleral tissue includes compressing the scleral tissue from a first size to a smaller second size within the distal axis.

P Example 40. A method according to P Example 39, wherein the size and shape of the distal shaft is designed to be inserted into the anterior chamber through a self-sealing incision in the cornea of the eye.

P Example 41. The method according to P Example 40 also includes deploying compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle.

P Example 42. A method according to P Example 41, wherein the compressed scleral tissue deployed from the distal axis recovers to the first size.

P Example 43. The method according to P Example 42 also includes treating glaucoma with compressed scleral tissue.

P Example 44. A method according to P Example 41, wherein deploying compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle includes deploying the compressed scleral tissue at least partially within Schlemm's canal and at least partially within the anterior chamber, or at least partially between the ciliary body and sclera of the eye, or at least partially within a cyclodialysis cleft.

P Example 45. A method according to P Example 41, wherein deploying compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle includes deploying the compressed scleral tissue within the cyclodialysis cleft so that the proximal end of the compressed scleral tissue avoids protruding within the anterior chamber.

P Example 46. A method according to P Example 41, wherein deploying compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle includes retracting the distal axis while maintaining the position of the compressed scleral tissue relative to the tissue layers.

P Example 47. A method according to P Example 41, wherein deploying compressed scleral tissue from the distal axis between tissue layers near the iridocorneal angle includes pushing the compressed scleral tissue out of the distal axis and into a position between the tissue layers.

P Example 48. A system for deploying an implant cut from biological tissue into a patient's eye, the system comprising: a delivery device comprising: a proximal handle; at least one actuator; and a distal connector; and a nose cone assembly comprising: a nose cone having a proximal region and a distal region; a connector on the proximal region of the nose cone, the connector being configured to reversibly engage with the distal connector of the delivery device; and a tubular shaft protruding from the distal region of the nose cone, the tubular shaft comprising one or more windows covered by a translucent or transparent material to reveal an inner cavity of the tubular shaft.

P Example 49. A system according to P Example 48, wherein one or more windows form a metering system for the tubular shaft, the metering system being configured to identify the insertion depth of the tubular shaft and/or the length of the implant within the lumen.

P Example 50. A system according to P Example 48, wherein the tubular shaft includes an introduction tube and an outer tube, the introduction tube is formed of an opaque material and the outer tube is formed of a translucent or transparent material.

P Example 51. A system according to P Example 48, wherein the tubular shaft includes a distal region distal to the one or more fenestrations.

P Example 52. A system according to P Example 51, wherein the distal region is bent away from the longitudinal axis of the proximal region of the tubular shaft so that the distal opening from the inner cavity is around an axis different from the longitudinal axis of the proximal region.

P Example 53. A system according to P Example 51, wherein the distal region is formed of a translucent or transparent material.

P Example 54. A system according to P Example 51, wherein the biological tissue is sclera or cornea.

P Example 55. A trephine device for minimally modifying a biologically derived tissue, the device being configured to cut the biologically derived tissue into an elongated tissue strip having a length and a width, wherein the length is greater than the width.

P Example 56. A device according to P Example 55, wherein the tissue strip is used for implantation into the patient's eye.

P Example 57. A device according to P Example 55, wherein the width is less than about 3 mm and the length is greater than about 3 mm.

P Example 58. A device according to P Example 55, wherein the biologically derived tissue includes scleral tissue or corneal tissue collected from a donor or patient.

P Example 59. The device according to P Example 55 also includes at least one sharp edge configured to cut the biologically derived tissue into the width.

Claims (143)

1. A system for deploying an implant cut from biological tissue into an eye of a patient, the system comprising:

A transfer device, the transfer device comprising:

A proximal housing;

At least one actuator; and

A distal coupler; and

A nose cone assembly, the nose cone assembly comprising:

A nose cone having a proximal region and a distal region;

a coupler on the proximal end region of the nose cone configured to reversibly engage with the distal coupler of the delivery device; and

A tubular shaft protruding from the distal region of the nose cone and comprising a lumen, the tubular shaft comprising one or more fenestrations extending through a sidewall of the shaft, the one or more fenestrations being covered by a translucent or transparent material so as to reveal the lumen of the tubular shaft.

2. The system of claim 1, wherein the one or more fenestrations form a metering system of the tubular shaft configured to identify a depth of insertion of the tubular shaft and/or a length of the implant within the lumen.

3. The system of claim 1, wherein the tubular shaft comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of the translucent or transparent material.

4. The system of claim 1, wherein the tubular shaft comprises a distal region distal to the one or more fenestrations.

5. The system of claim 4, wherein the distal region is curved away from a longitudinal axis of a proximal region of the tubular shaft such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

6. The system of claim 4, wherein the distal region is formed of a translucent or transparent material.

7. The system of claim 1, further comprising the implant.

8. The system of claim 7, wherein the biological tissue of the implant is scleral or corneal biological tissue.

9. A device for minimal modification of biologically derived tissue, the device comprising two blades separated by a gap, each blade having an inner face and at least one distal bevel forming a cutting edge, wherein the two blades are mounted at an angle relative to each other such that the inner faces are non-parallel and the distal bevels are parallel to each other, wherein the device is configured to cut the biologically derived tissue into an elongated strip having a length and a width, wherein the length is greater than the width.

10. The device of claim 9, wherein the distal bevel is orthogonal to the tissue.

11. The device of claim 9, wherein the strap is configured to be implanted in an eye of a patient.

12. The device of claim 9, wherein the width is less than about 3mm and the length is greater than about 3mm.

13. The device of claim 9, wherein the biologically derived tissue comprises scleral tissue or corneal tissue harvested from a donor or patient.

14. A cassette for use with a system for preparing an implant and inserting the implant endometrically into an eye, the cassette comprising:

a lower component having a planar upper surface sized and shaped to receive a piece of material to be cut into an implant;

An upper member movably coupled to the lower member between an open configuration and a closed configuration, the upper member having a lower surface arranged to oppose the upper surface of the lower member when the upper member is in the closed configuration; and

A pair of blades configured to extend below a lower surface of the upper member to cut a piece of the material into the implant.

15. The cartridge of claim 14, wherein the piece of material remains fixed relative to the lower member when the upper member is in the closed configuration.

16. The cartridge of claim 14, further comprising an actuator configured to cause the pair of blades to cut the pieces of material into the implant.

17. The cartridge of claim 16, wherein the actuator comprises a lever configured to move the pair of blades relative to the upper surface.

18. The cartridge of claim 14, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

19. The cartridge of claim 18, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

20. The cartridge of claim 19, wherein the apertures of the upper and lower members are each shaped to prevent rotation relative to the distal projections of the first and second handle portions.

21. The cartridge of claim 19, wherein the aperture and the distal protrusion are coupled by a slip fit or an interference fit.

22. The cartridge of claim 19, wherein expanding the first and second handle portions expands the lower and upper members from the closed configuration toward the open configuration.

23. The cartridge of claim 14, wherein the pair of blades are separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

24. The cartridge of claim 23, wherein the distal ramp is orthogonal to the upper surface.

25. The cassette of claim 14, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

26. A system for preparing an implant for implantation in an eye of a patient and inserting the implant into an eye of a patient, the system comprising:

a cassette configured to receive a piece of material and comprising a pair of blades configured to cut the piece to form an implant from the piece; and

A delivery instrument comprising a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye, wherein the distal portion comprises a lumen having an elongate tubular member sized to receive the implant cut from the segment with the pair of blades.

27. The system of claim 26, further comprising an actuator configured to cause the pair of blades to cut the pieces of material into the implant.

28. The system of claim 27, wherein the actuator comprises a rod configured to move the pair of blades relative to the tile.

29. The system of claim 27, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

30. The system of claim 29, wherein the cartridge comprises a lower member having an upper surface and an upper member having a lower surface, the pair of blades extending below the lower surface of the upper member.

31. The system of claim 30, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive a distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive a distal protrusion of the second handle portion.

32. The system of claim 31, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal protrusions of the first and second handle portions.

33. The system of claim 31, wherein the first and second holes and the distal protrusion are coupled by a slip fit or an interference fit.

34. The system of claim 30, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

35. The system of claim 26, wherein the pair of blades are separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

36. The system of claim 35, wherein the distal bevel is orthogonal to the tile.

37. The system of claim 26, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

38. The system of claim 26, wherein the elongate tubular member comprises one or more fenestrations extending through a sidewall of the tubular member.

39. The system of claim 38, wherein the one or more fenestrations are covered by a translucent or transparent material so as to reveal the lumen of the tubular member.

40. The system of claim 38, wherein the one or more fenestrations form a metering system of the tubular member configured to identify a depth of insertion of the tubular member and/or a length of the implant within the lumen.

41. The system of claim 38, wherein the tubular member comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

42. The system of claim 38, wherein the tubular member comprises a distal region distal to the one or more fenestrations.

43. The system of claim 42, wherein the distal region is curved away from a longitudinal axis of the proximal region of the tubular member such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

44. The system of claim 42, wherein the distal region is formed of a translucent or transparent material.

45. The system of claim 26, wherein the material comprises a bio-derived material suitable for implantation in an eye.

46. The system of claim 45, wherein the biologically derived material comprises tissue, allograft material or xenograft material harvested from a donor or from a patient.

47. The system of claim 26, wherein the material comprises an engineered material or a 3D printed material suitable for implantation in an eye.

48. The system of claim 26, wherein the implant comprises one or more therapeutic agents.

49. The system of claim 26, wherein the distal region of the elongate tubular member is at least one of angled or curved or flexible.

50. The system of claim 26, wherein the lumen comprises a circular cross-section.

51. The system of claim 26, further comprising an actuator on the housing configured to retract the elongate tubular member from the implant while maintaining implant position relative to adjacent ocular tissue.

52. The system of claim 51, further comprising an inner elongate member configured to contact a proximal end of the implant when the elongate tubular member is retracted by the actuator.

53. The system of claim 51, wherein the actuator on the housing comprises at least one of a dial, a slider, or a button.

54. The system of claim 26, wherein the distal-most end of the elongate tubular member is blunt to allow dissection of ocular tissue without cutting ocular tissue.

55. A system for preparing an implant for implantation in an eye of a patient and inserting the implant into an eye of a patient, the system comprising:

a cartridge configured to contain and retain material within the cartridge;

at least one cutting member configured to cut the material to form an implant from the material; and

A delivery instrument comprising a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye, wherein the distal portion comprises a lumen having an elongate tubular member.

56. The system of claim 55, wherein a distal-most end of the elongate tubular member is configured to dissect tissue for implantation in schlemm's canal or transscleral implantation.

57. The system of claim 55, wherein the housing further comprises a movable inner elongate member configured to advance the implant through the lumen and out of the distal opening of the elongate tubular member.

58. The system of claim 55, further comprising an actuator configured to cause the at least one cutting member to cut the material to form the implant.

59. The system of claim 58, wherein the actuator comprises a rod configured to move the at least one cutting member relative to the material.

60. The system of claim 58, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

61. The system of claim 60, wherein the cartridge comprises a lower component having an upper surface and an upper component having a lower surface, the at least one cutting member comprising a pair of blades extending below the lower surface of the upper component.

62. The system of claim 61, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

63. The system of claim 62, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal protrusions of the first and second handle portions.

64. The system of claim 62, wherein the first and second apertures and the distal protrusion are coupled by a slip fit or an interference fit.

65. The system of claim 61, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

66. The system of claim 55, wherein the at least one cutting member comprises a pair of blades separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

67. The system of claim 66, wherein the distal bevel is orthogonal to the material.

68. The system of claim 55, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

69. The system of claim 55, wherein the elongate tubular member comprises one or more fenestrations extending through a sidewall of the tubular member.

70. The system of claim 69, wherein the one or more fenestrations are covered by a translucent or transparent material to reveal the lumen of the tubular member.

71. The system of claim 69, wherein the one or more fenestrations form a metering system of the tubular member configured to identify a depth of insertion of the tubular member and/or a length of the implant within the lumen.

72. The system of claim 69, wherein the tubular member comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

73. The system of claim 69, wherein the tubular member comprises a distal region distal to the one or more fenestrations.

74. The system of claim 73, wherein the distal region is curved away from a longitudinal axis of the proximal region of the tubular member such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

75. The system of claim 73, wherein the distal region is formed of a translucent or transparent material.

76. A system for preparing an implant and inserting the implant endometrically into an eye, the system comprising:

A blade cartridge configured to move between an open configuration and a closed configuration for loading a piece of material into the blade cartridge, the cartridge comprising:

a lower component having an upper surface configured to receive a piece of the material;

An upper member having a lower surface configured to abut against a patch of the material when the cartridge is in a closed configuration; and

A pair of blades and a spacer defining a gap between the blades,

Wherein the pair of blades are configured to extend below the lower surface of the upper member to penetrate the piece of material at two locations to form a strip of the material having a width that is narrower than a width of the piece of material when the blade cartridge is moved to a closed configuration.

77. The system of claim 76, wherein the upper member and the lower member are hinged relative to one another.

78. The system of claim 76, wherein the upper member and the lower member are reversibly coupled to each other.

79. The system of claim 76, wherein the gap defined by the spacer determines a width of the strip.

80. The system of claim 76, wherein each blade of the pair of blades comprises a single bevel edge or a double bevel edge.

81. The system of claim 76, further comprising an actuator configured to cause the pair of blades to cut the piece to form the strip.

82. The system of claim 81, wherein the actuator comprises a rod configured to move the pair of blades relative to the upper surface.

83. The system of claim 81, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

84. The system of claim 83, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

85. The system of claim 84, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal projections of the first and second handle portions.

86. The system of claim 84, wherein the first and second apertures and the distal protrusion are coupled by a slip fit or an interference fit.

87. The system of claim 84, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

88. The system of claim 76, wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

89. The system of claim 88, wherein the distal bevel is orthogonal to the upper surface.

90. The system of claim 76, further comprising the piece of material.

91. The system of claim 76, wherein the material comprises a bio-derived material suitable for implantation into an eye.

92. The system of claim 91, wherein the biologically-derived material comprises tissue harvested from a donor or from an eye.

93. The system of claim 91, wherein the biologically derived material is an autograft material, an allograft material, or a xenograft material.

94. The system of claim 76, wherein the material is an engineering organization.

95. The system of claim 94, wherein the engineered tissue is a 3D printed material suitable for implantation.

96. The system of claim 76, wherein the implant comprises one or more therapeutic agents.

97. The system of claim 76, further comprising a conveyor, the conveyor comprising:

A proximal housing having one or more actuators;

An inner pusher; and

An outer tube including an inner lumen sized to receive the inner pusher.

98. The system of claim 97, wherein the inner pusher is configured to be advanced distally using the one or more actuators of the proximal housing of the delivery device.

99. The system of claim 97, wherein the lumen of the outer tube is sized to receive the width of the strip.

100. The system of claim 97, wherein the outer tube is configured to inject a viscoelastic material using the inner pusher as a plunger.

101. The system of claim 97, wherein at least a proximal portion of the outer tube extends along a longitudinal axis, and wherein a distal region of the outer tube is angled away from the longitudinal axis.

102. The system of claim 97, wherein the distal-most end of the outer tube is blunt to allow dissection between tissue of an eye without cutting the tissue.

103. The system of claim 97, wherein the outer tube includes one or more fenestrations extending through a sidewall of the outer tube.

104. The system of claim 103, wherein the one or more fenestrations are covered by a translucent or transparent material to reveal the lumen of the outer tube.

105. The system of claim 103, wherein the one or more fenestrations form a metering system of the outer tube configured to identify a depth of insertion of the outer tube and/or a length of the implant within the lumen.

106. The system of claim 103, wherein the outer tube comprises an introduction tube formed of an opaque material and an outer tubular member formed of a translucent or transparent material.

107. The system of claim 103, wherein the outer tube comprises a distal region distal to the one or more fenestrations.

108. The system of claim 107, wherein the distal region is curved away from a longitudinal axis of a proximal region of the outer tube such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

109. The system of claim 107, wherein the distal region is formed of a translucent or transparent material.

110. The system of claim 97, wherein a distal region of the outer tube has a maximum outer diameter of no greater than about 1.3 mm.

111. The system of claim 97, wherein the outer tube is a hypotube having an inner diameter of less than about 0.036 "to about 0.009".

112. The system of claim 97, wherein the outer tube is coupled to a first actuator of the one or more actuators and the inner pusher is coupled to a second actuator.

113. The system of claim 97, wherein distal advancement of the inner pusher pushes the implant distally through the lumen of the outer tube into a ready position proximate to a distal opening from the lumen of the outer tube.

114. The system of claim 113, wherein proximal retraction of the outer tube withdraws the implant for deployment into an eye while the inner pusher remains stationary relative to the housing.

115. A system for deploying an implant cut from biological tissue into an eye of a patient, the system comprising:

A transfer device, the transfer device comprising:

A proximal housing;

At least one actuator coupled to the pushrod; and

A distal coupler; and

A nose cone assembly, the nose cone assembly comprising:

A nose cone having a proximal region and a distal region;

a coupler on the proximal end region of the nose cone configured to reversibly engage with the distal coupler of the delivery device; and

A tubular shaft protruding from the distal region of the nose cone and comprising a lumen, the tubular shaft comprising a distal region and a proximal region, wherein the distal region is curved away from a longitudinal axis of the proximal region.

116. The system of claim 115, wherein the distal region forms a tangential arc having a radius between 10-20 mm.

117. The system of claim 115, wherein the distal region is beveled such that an opening from the lumen is elongated and a distal-most tip of the shaft extends beyond the opening.

118. The system of claim 115, wherein the distal region has a bevel.

119. The system of claim 118, wherein the bevel is about 10-45 degrees.

120. The system of claim 118, wherein the opening near the proximal heel of the bevel is circular and the opening near the distal-most end of the shaft is square.

121. The system of claim 115, wherein the pushrod is sized to extend through the lumen of the shaft to the opening.

122. The system of claim 115, wherein the pushrod is formed from nitinol or stainless steel.

123. The system of claim 115, wherein the pushrod is a monofilament or a braided member.

124. The system of claim 115, wherein the pushrod is a completely cylindrical element without an inner lumen.

125. The system of claim 115, wherein the pushrod has a proximal region, a distal region, and an intermediate region between the proximal region and the distal region.

126. The system of claim 125, wherein the intermediate region has greater flexibility than the proximal region.

127. The system of claim 126, wherein the greater flexibility of the intermediate region is configured to translate through a curved distal region of the shaft.

128. The system of claim 125, wherein an outer diameter of the pushrod varies from a proximal region of the pushrod to a distal region of the pushrod.

129. The system of claim 125, wherein an outer diameter of the distal region is greater than an outer diameter of the intermediate region.

130. The system of claim 129, wherein the outer diameter of the distal region is 0.525mm-0.575mm.

131. The system of claim 130, wherein the intermediate region has an outer diameter of 0.200mm-0.300mm.

132. The system of claim 131, wherein the lumen of the shaft has an inner diameter of 0.600mm-0.900 mm.

133. The system of claim 125, wherein the intermediate region has a length of about 8-10 mm.

134. The system of claim 125, wherein the distal region of the pushrod has a length of about 2mm-5 mm.

135. The system of claim 115, wherein the at least one actuator comprises a second actuator and a first actuator configured to slide within a slider track of the housing.

136. The system of claim 135, wherein the first actuator comprises an outer portion positioned outside the housing and an inner portion positioned inside the housing.

137. The system of claim 136, wherein the inner portion comprises a flexing portion having protrusions, the flexing portion being movable between a compressed position and a relaxed configuration.

138. The system of claim 137, wherein the proximal housing has a backstop positioned below a slider track of the housing.

139. The system of claim 138, the protrusion engaging the backstop when the flexure is in a relaxed configuration, thereby preventing proximal movement of the first actuator relative to the housing.

140. The system of claim 115, wherein the tubular shaft comprises one or more fenestrations extending through a sidewall of the shaft, the one or more fenestrations covered by a translucent or transparent material to reveal the lumen of the tubular shaft.

141. The system of claim 140, wherein the one or more fenestrations form a metering system of the tubular shaft configured to identify a depth of insertion of the tubular shaft and/or a length of the implant within the lumen.

142. The system of claim 115, wherein the tubular shaft comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

143. The system of claim 115, wherein the distal region is formed of a translucent or transparent material.