Devices and systems for cutting, loading, and delivering biologic intraocular implants for increasing aqueous humor outflow and reducing intraocular pressure - Patents.com

Abstract

A system for treating an eye comprising tissue stored within a lumen of an elongated cannula, the tissue comprising sclera, amniotic membrane, or acellular biomatrix tissue, the system having an elongated form factor. Related devices, systems, and methods are provided.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application Nos. 63 / 427,552, filed November 23, 2022, 63 / 488,920, filed March 7, 2023, and 63 / 584,804, filed September 22, 2023, the entire contents of which are incorporated by reference in their entirety. [Background technology]

[0002] The mainstay of ophthalmic surgery for glaucoma is increasing aqueous outflow from the eye. There are various approaches to such surgery, including: 1) ab externo trabeculectomy or shunting, which involves cutting the conjunctiva and sclera and penetrating the eye to provide transscleral outflow; 2) ab interno trabecular or transscleral aqueous outflow stenting or shunting, using implantable hardware-based devices or non-implantable ablative cutters such as dual blades and trabeculectomes; and 3) ab interno supraciliary body stenting, using implantable non-biologic hardware implants.

[0003] Current ab interno stenting devices and methods are based on non-biologic hardware materials such as polyimide, polyethersulfone, titanium, polystyrene-block-isobutylene-block-styrene, etc. Such non-biologic hardware-based implantable devices have significant drawbacks, including the potential for ocular tissue damage, including extensive erosion, fibrosis, and endothelial cell loss.

[0004] In view of the above, there is a need for improved devices and methods related to ophthalmic surgery for the treatment of glaucoma. Summary of the Invention

[0005] In one aspect, a system for treating glaucoma in an eye is disclosed, including a perforation system having a cutter configured to cut a biological tissue material into an implant. The biological tissue material includes amniotic tissue configured to elute one or more healing factors from the amniotic tissue. The system includes a container having a reservoir sized to receive a predetermined volume of liquid and a delivery system. The delivery system includes a cartridge having a nosecone with a coupler extending from a proximal end region of the nosecone. The delivery system includes a delivery cannula extending from a distal end region of the nosecone, the delivery cannula having a lumen and a distal opening to the lumen. The delivery system includes a proximal housing configured to engage with the coupler of the cartridge.

[0006] The reservoir can be sized to suspend the implant in a volume of liquid such that when a distal opening of the delivery cannula is positioned near the implant within the reservoir and a vacuum is applied through the delivery cannula, the implant is drawn into the distal opening of the delivery cannula. The cartridge can be configured to couple to a vacuum source. The vacuum source can be configured to draw the implant into the distal opening of the delivery cannula when the vacuum source is coupled to the cartridge and activated. The vacuum source can include a syringe having a syringe barrel with a luer at its distal end and a plunger disposed within the syringe barrel. The piercing system can further include an adapter having a first end sized and shaped to couple to the luer of the syringe and a second end sized and shaped to receive the coupler of the cartridge.

[0007] The container can further include a loading channel extending outward from the reservoir, the loading channel having a first end region configured to receive the distal end region of the delivery cannula and a second end in fluid communication with the reservoir. The container can further include a loading post having an outer diameter sized to be received within the distal opening of the delivery cannula. The proximal housing can further include a pusher extendable through the lumen of the delivery cannula toward the distal opening. Once the implant is loaded into the delivery cannula and the cartridge is coupled to the proximal housing, the implant can be configured to be compressed between the loading post and the pusher of the proximal housing to expel liquid that entered the delivery cannula during loading.

[0008] The system can further include a second biological tissue material. The second biological tissue material can include scleral tissue or corneal tissue. The liquid can be a viscoelastic or saline solution. The implant can be sized to be received within the distal opening. The implant can be oversized relative to the lumen of the delivery cannula. The oversized implant can compress when placed within the lumen of the delivery cannula and expand upon deployment into the eye and release from the lumen of the delivery cannula.

[0009] In related aspects, a system for treating glaucoma is provided, including a first implant, a second implant, and a delivery cannula. The first implant is dehydrated biological tissue cut to a first width sized to be received within the lumen of the delivery cannula. The first implant is configured to rehydrate upon deployment within the eye at an implantation location and expand to a second width greater than the first width to provide scaffolding at the implantation location. The second implant includes amniotic tissue configured to elute one or more healing factors derived from the amniotic tissue near the implantation location of the first implant.

[0010] In a related aspect, a method of treating glaucoma in an eye is provided, comprising implanting a first implant containing dehydrated biological tissue cut into a first implant at a target location in the eye. The method includes implanting a second implant near the target location of the first implant, the second implant being amniotic tissue configured to elute one or more healing factors from the amniotic tissue. The method includes opening the target location of the first implant as the first implant expands from a first size to a larger size upon deployment in the eye and promoting outflow of aqueous humor from the anterior chamber of the eye.

[0011] In a related aspect, a system for treating an eye is provided, the system including tissue stored within a lumen of an elongated cannula. The tissue is amniotic tissue. The tissue can have a length greater than 3 mm. The tissue can have an outer dimension less than 3 mm. The tissue can have a length of approximately 2 mm to 11 mm. The system can further include an impermeable membrane covering an opening from the lumen of the elongated cannula configured to prevent fluid loss. The elongated cannula with the tissue within the lumen can be packaged in a radiation-stable container. The elongated cannula can be straight or curved. The elongated cannula can further include a nosecone having a coupling mechanism at a proximal end of the nosecone. The elongated cannula can protrude from a distal end of the nosecone. The system can further include a handpiece having a distal coupler configured to engage with the coupling mechanism on the nosecone to form a delivery system. The handpiece can be configured to deploy the tissue from the lumen into the eye. The elongate cannula may have a beveled distal tip at its distal opening from the lumen. The elongate cannula may comprise a hydrophobic or hydrophilic material.

[0012] In a related aspect, a system for treating an eye is provided, comprising amniotic tissue modified into an elongated shape having a width of approximately 100 microns to 2000 microns and configured to elute one or more healing factors from the amniotic tissue. The system can further include a perforator configured to modify the amniotic tissue by cutting the amniotic tissue into an elongated shape. The perforator can include multiple blades configured to make parallel cuts to form multiple strips, each strip having an elongated shape. The multiple blades can be circular and configured to rotate relative to the perforator handle. The multiple blades can rotate passively when a user urges the perforator along the amniotic tissue. The multiple blades can be rotated powered by a motor. The perforator can further include a base having a material with a durometer between Shore 60A and Shore 60D. The system can further include an implant cartridge having an elongated cannula with a lumen extending between a proximal opening and a distal opening. The system may further include a loader for inserting the at least one strip into the lumen of the elongated cannula. The loader may be positioned relative to the elongated cannula of the implant cartridge and may place the at least one strip into the lumen through the distal opening. The loader may use positive pressure to inject the at least one strip through the distal opening. The loader may use negative pressure to aspirate the at least one strip through the distal opening.

[0013] In a related aspect, a system for treating glaucoma in an eye is provided, comprising: a first biological tissue material cut into a first implant sized and shaped for intraocular implantation at a target location within the eye; and a second biological tissue material cut into a second implant sized and shaped for intraocular implantation at or near the target location within the eye. The first biological tissue material can comprise scleral tissue or corneal tissue, and the second biological tissue material can comprise amniotic tissue configured to elute one or more healing factors from the amniotic tissue near the target location within the eye.

[0014] The target location within the eye can be the suprachoroidal space, the supraciliary space, Schlemm's canal, the anterior chamber, the posterior chamber, the vitreous body, the epiretinal, or the subretinal. The first implant can have an elongated shape with a length of about 3 mm to about 11 mm, a width of about 0.10 mm to about 3 mm, and a thickness of about 0.05 mm to about 1 mm. The second implant can have an elongated shape with a length of about 3 mm to about 11 mm, a width of about 0.10 mm to about 3 mm, and a thickness of about 0.05 mm to about 1 mm.

[0015] In a related aspect, a system for treating glaucoma in an eye is provided, including a puncture system having a cutter configured to cut biological tissue material into an implant and a container having a reservoir sized to receive a predetermined volume of liquid. The system further includes a delivery system including a cartridge and a proximal housing configured to engage a coupler of the cartridge. The cartridge includes a nosecone having a coupler extending from a proximal end region of the nosecone, and a delivery cannula extending from a distal end region of the nosecone, the delivery cannula having a lumen and a distal opening to the lumen.

[0016] The reservoir can be sized to suspend the implant in a volume of liquid such that when a distal opening of a delivery cannula is positioned near the implant in the reservoir and a vacuum is applied through the delivery cannula, the implant is drawn into the distal opening of the delivery cannula. The cartridge can be configured to couple to a vacuum source. The vacuum source can be configured to draw the implant into the distal opening of the delivery cannula when the vacuum source is coupled to the cartridge and activated. The vacuum source can include a syringe having a syringe barrel with a luer at its distal end and a plunger disposed within the syringe barrel. The piercing system can further include an adapter having a first end sized and shaped to couple with the luer of the syringe and a second end sized and shaped to receive the coupler of the cartridge. The container can further include a loading channel extending outward from the reservoir. The loading channel can have a first end region configured to receive the distal end region of the delivery cannula and a second end in fluid communication with the reservoir. The container can further include a loading post having an outer diameter sized to be received within the distal opening of the delivery cannula. The proximal housing can further include a pusher extendable through the lumen of the delivery cannula toward the distal opening. Once the implant is loaded into the delivery cannula and the cartridge is coupled to the proximal housing, it can be compressed between the loading post and the pusher of the proximal housing to expel liquid that entered the delivery cannula during loading. The system can further include a biological tissue material. The biological tissue material can be scleral tissue. The liquid can be viscoelastic or saline. The implant can be sized to be received within the distal opening. The implant can be oversized relative to the lumen of the delivery cannula. An oversized implant can be compressed when placed within the lumen of the delivery cannula and expand upon deployment into the eye and ejection from the lumen of the delivery cannula.

[0017] In a related aspect, a system for treating glaucoma is provided, including an implant and a delivery cannula. The implant is dehydrated biological tissue cut to a first width sized to be received within the lumen of the delivery cannula. The implant is configured to rehydrate and expand to a second width greater than the first width upon deployment within the eye.

[0018] In a related aspect, a method of treating glaucoma is provided that uses dehydrated biological tissue cut into an implant having a first size that expands upon deployment within the eye to a larger size, the larger size implant opening a space within the eye for improved outflow of aqueous humor from the anterior chamber.

[0019] In a related aspect, a method is provided for preparing an implant for implantation into a patient's eye and inserting the implant into the patient's eye. The method includes cutting a patch of material with a cutting member to form an implant from the patch. The method includes coupling a cartridge to an aspiration device. The cartridge includes a nosecone and a delivery cannula extending from a distal end of the nosecone. At least a distal end region of the delivery cannula is sized and shaped for insertion into the anterior chamber of the eye, the delivery cannula comprising a lumen. The method includes immersing the distal end region of the delivery cannula in a volume of a viscous material containing the implant and aspirating the implant into the lumen of the delivery cannula using the aspiration device.

[0020] The method can further include transferring the cartridge from the aspiration device to a delivery device, inserting a distal end region of the delivery cannula into the anterior chamber of the eye, positioning the distal end region of the delivery cannula adjacent to ocular tissue, and actuating the delivery device to deploy the implant from the delivery cannula and through at least a portion of the lumen such that the implant engages the ocular tissue. The method can further include delivering a viscous material through the delivery cannula.

[0021] In a related aspect, a system for treating an eye is provided, comprising tissue stored within a lumen of an elongated cannula. The tissue can be scleral tissue or acellular biomatrix tissue. The tissue can have a length greater than 3 mm. The tissue can have an outer dimension less than 3 mm. The tissue can have a length of approximately 2 mm to 11 mm. The system can further comprise an impermeable membrane covering an opening from the lumen of the elongated cannula configured to prevent fluid loss. The elongated cannula with the tissue within the lumen can be packaged in a radiation-stable container. The elongated cannula can be straight or curved. The elongated cannula can further comprise a nosecone having a coupling mechanism at a proximal end of the nosecone. The elongated cannula can protrude from a distal end of the nosecone.

[0022] The system can further include a handpiece having a distal coupler configured to engage a coupling mechanism on a nosecone to form a delivery system. The handpiece can be configured to deploy tissue from the lumen into the eye. The elongate cannula can include a beveled distal tip at a distal opening from the lumen. The elongate cannula can include a hydrophobic or hydrophilic material.

[0023] In a related aspect, a system for treating an eye is provided, the system including scleral tissue processed into an elongated shape having a width of approximately 100 microns to 2000 microns. The system can further include a perforator configured to process the scleral tissue by cutting the scleral tissue into elongated shapes. The perforator can include multiple blades configured to make parallel cuts to form multiple scleral strips, each having an elongated shape. The multiple blades can be circular and configured to rotate relative to the perforator handle. The multiple blades can rotate passively when a user moves the perforator along the scleral tissue. The multiple blades can be rotated powered by a motor. The perforator can further include a base having a material with a durometer between Shore 60A and Shore 60D. The blades can be angled relative to the beveled grinding portion of the blade. The system can further include a planer configured to lower the height of the scleral tissue. The system can further include an implant cartridge having an elongated cannula with a lumen extending between a proximal opening and a distal opening. The system may further include a loader for inserting at least one scleral strip into the lumen of the elongated cannula. The loader may be positioned relative to the elongated cannula of the implant cartridge and may place the at least one scleral strip into the lumen through the distal opening. The loader may use positive pressure to inject the at least one scleral strip through the distal opening. The loader may use negative pressure to aspirate the at least one scleral strip through the distal opening.

[0024] In a related aspect, an ocular stent delivery system is provided having an ocular stent and a cartridge containing the ocular stent. The cartridge includes a nosecone having a proximal end region and a distal end region, and an elongate shaft extending from the distal end region of the nosecone. The elongate shaft includes a cannula having a lumen extending between a proximal opening and a distal opening. The cannula has a curved portion located between the proximal opening and the distal opening. The cartridge includes a pusher at least partially disposed within the lumen of the cannula to span the curved portion. The proximal end of the pusher is located outside the proximal opening of the cannula and within the proximal end region of the nosecone. The system includes a proximal handpiece configured to couple with the cartridge. The proximal handpiece includes a housing defining a distal opening sized to receive the proximal end region of the nosecone, a carriage located within the housing and configured to be releasably coupled to the proximal end region of the nosecone, and an actuation mechanism configured to retract the cartridge relative to the housing such that the pusher deploys the ocular stent through the distal opening.

[0025] The actuation mechanism may include an actuator and a spring. The actuator may further include a first portion, a second portion, and a hinge, the hinge being fixed to the carriage. When the actuation mechanism is in an armed configuration, the carriage may be in a distal-most position relative to the housing, the spring is compressed, and the first portion is biased upward. The second portion of the actuator may be biased downward to engage with the carriage. The second portion of the actuator may be biased upward to engage with the housing. The system may further include a buttress secured within a region of the housing near the distal opening, the buttress having a distally-facing bearing surface. When the cartridge is coupled to the proximal handpiece, the proximal end of the pusher may be positioned adjacent to the distally-facing bearing surface of the buttress. Actuation of the actuation mechanism may move the carriage proximally through the housing. Proximal movement of the carriage through the housing can retract the cartridge against the buttress, with the distally facing bearing surface of the buttress abutting the proximal end of the pusher and preventing the pusher from retracting with the cartridge. The pusher can be held within the cannula lumen solely by friction between the pusher and the inner surface of the cannula at the curved portion. The spring force can be greater than the friction between the pusher and the inner surface of the cannula at the curved portion. The speed of movement of the carriage can be controlled by the spring. The speed of movement of the carriage can be controllable by a user with the aid of the spring. The actuation mechanism can be configured to be re-armed for multiple actuations. The cartridge can further include an outer tubular member extending across at least the distal opening of the cannula and forming the distal end of the elongate shaft. The outer tubular member can be translucent or transparent. A distal end region of the outer tubular member can be curved and define the distal opening of the elongate shaft. The ocular stent can be minimally processed biological tissue.The minimally processed biological tissue can be amniotic tissue, sclera tissue, or acellular biomatrix tissue having dimensions sized to be received within a lumen. The minimally processed biological tissue can be cut to lengths of about 2 mm to about 11 mm.

[0026] In some variations, one or more of the following may optionally be included in any workable combination in the above methods, apparatus, devices, and systems. Further details are set forth in the accompanying drawings and the description below. Other features and advantages will be apparent from the description and drawings. [Brief explanation of the drawings]

[0027] These and other aspects are described in detail with reference to the following drawings. Generally, the figures are not to scale, either absolute or relative, and are intended for illustrative purposes. Also, the relative placement of features and elements may be altered for clarity of illustration.

[0028] [Figure 1A] 1 is a cross-sectional view of a human eye showing the anterior chamber and vitreous cavity of the eye with a living tissue stent positioned in an exemplary location within the eye. [Figure 1B] FIG. 1B is a detailed view of the eye of FIG. 1A after the shape change of the stent deployed in the eye. [Figure 2A] FIG. 1 is a box diagram illustrating a treatment system including a perforation system and a delivery system. [Figure 2B] 2B is an embodiment of the treatment system of FIG. 2A. [Figure 3A] FIG. 1 is a box diagram illustrating an organization system including a drilling system, a loading system, and an implant cartridge. [Figure 3B] FIG. 1 is a box diagram illustrating a manufacturing process for forming a biological tissue stent. [Figure 4A] 1 is an embodiment of a perforator of a perforation system for creating multiple biological tissue stents in a single cutting operation. [Figure 4B]4B is a schematic front end view of the blade of the perforator of FIG. 4A. FIG. [Figure 4C] FIG. 4B is a schematic side view of the perforator of FIG. 4A. [Figure 4D] 10 is an embodiment of a perforator having fixed rollers that pinch and drive tissue through the perforator. [Figure 4E] 1 shows a handle for a perforator. [Figure 4F] 10 is another embodiment of a perforator for creating multiple biological tissue stents in one cutting motion. [Figure 5A] FIG. 1 is a schematic diagram of an embodiment of a planer of a drilling system. [Figure 5B] 5B is a schematic diagram illustrating an exemplary blade shape of the planer of FIG. 5A. FIG. [Figure 5C] FIG. 1 is a schematic diagram showing a patch of material being scraped with a planer. [Figure 5D] 10A-10C are perspective views of the planer of the drilling system from different angles. [Figure 5E] 10A-10C are perspective views of the planer of the drilling system from different angles. [Figure 5F] 10A-10C are perspective views of the planer of the drilling system from different angles. [Figure 6A] FIG. 1 is a perspective view of the cutter in an open configuration with the bearing surface exposed. [Figure 6B] FIG. 6B is a detailed view of the bearing surface of the cutter of FIG. 6A. [Figure 6C] FIG. 6B is a side view of the cutter of FIG. 6A transitioning from an open configuration to a closed configuration. [Figure 6D] This is an example of a parallel blade cutter. [Figure 6E] This is an example of a non-parallel blade of a cutter. [Figure 6F] This is an example of a die cut punch for a cutter. [Figure 6G] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6H] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6I]1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6J] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6K] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6L] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 6M] 1A-1C are schematic diagrams illustrating exemplary implant shapes formed using a die-cut punch. [Figure 7A] FIG. 1 is a perspective view of an embodiment of a loading system incorporating a loader and loading cartridge engaged with a cannula of an implant cartridge. [Figure 7B] FIG. 10 is a partial perspective view of a cannula received in a receptacle of a loader. [Figure 7C] FIG. 7B is a perspective view of the loading cartridge of FIG. 7A. [Figure 7D] FIG. 7D is a cutaway side view of the loading cartridge of FIG. 7C showing the stent. [Figure 7E] FIG. 7C is a cross-sectional view of FIG. 7B before the stent is injected into the cannula. [Figure 7F] FIG. 7C is a cross-sectional view of FIG. 7B after the stent has been injected into the cannula. [Figure 8A] 1 is an embodiment of a container for suspending an implant for loading into a delivery cannula. [Figure 8B] 1 is an embodiment of a container for suspending an implant for loading into a delivery cannula. [Figure 8C] FIG. 1 is a side view of a reservoir containing an implant prior to loading. [Figure 8D] FIG. 12 is an end view of a reservoir containing an implant prior to loading. [Figure 8E] FIG. 1 is a side view of a reservoir containing an implant prior to loading. [Figure 8F] FIG. 12 is an end view of a reservoir containing an implant prior to loading. [Figure 9A] FIG. 10 is an exploded side view showing an adapter for coupling a delivery cannula to a vacuum source. [Figure 9B] FIG. 8C is an assembled side view of a delivery cannula inserted into the reservoir of the container of FIG. 8B for loading the implant. [Figure 9C] FIG. 10 is a detailed view of the distal end region of the delivery cannula inside the reservoir for aspirating the implant. [Figure 10A] FIG. 8C is a side view of a delivery cannula positioned on the fill post of the reservoir of FIG. 8B. [Figure 10B] FIG. 10B is a detailed view of the delivery cannula of FIG. 10A. [Figure 11A] 1 is an embodiment of the packaging of an implant cartridge. [Figure 11B] 10 is another embodiment of the packaging for the implant cartridge. [Figure 11C] 1 is a schematic diagram of an embodiment of the packaging of the implant cartridge. [Figure 12A] FIG. 13 is a perspective view of the proximal end of the implant cartridge. [Figure 12B] 12B is a perspective view of the distal end of a handpiece configured to mate with the implant cartridge of FIG. 12A. FIG. [Figure 12C] FIG. 10 is a perspective view of the distal end of the implant cartridge and handpiece coupled together. [Figure 13A] FIG. 10 is a side cross-sectional view of an implant cartridge in a loaded position prior to installation in a handpiece. [Figure 13B] FIG. 10 is a side cross-sectional view of an implant cartridge installed in a handpiece in a standby position. [Figure 13C] FIG. 10 is a side cross-sectional view of an implant cartridge installed in a handpiece in a deployed position. [Figure 14A] FIG. 13 is a perspective view of the proximal end of the implant cartridge. [Figure 14B] FIG. 14B is a perspective proximal end view of a handpiece configured to mate with the implant cartridge of FIG. 14A. [Figure 14C] FIG. 14C is a perspective proximal end view of the implant cartridge and handpiece of FIGS. 14A and 14B coupled together. [Figure 14D] FIG. 14D is a cross-sectional view of the delivery system of FIG. 14C along line DD. [Figure 14E] FIG. 14B is a cross-sectional view of the implant cartridge of FIG. 14A taken along line EE. [Figure 14F] FIG. 14B is an exploded side view of the implant cartridge of FIG. 14A. [Figure 15A] FIG. 1 is a cross-sectional view of a delivery system with a carriage in a loaded state. [Figure 15B] FIG. 15B is a cross-sectional view of the delivery system of FIG. 15A after retraction of the carriage. [Figure 16A] 1 shows a dehydrated implant. [Figure 16B] 16B shows the implant of FIG. 16A after rehydration. [Figure 16C] FIG. 13 is a partial perspective view of a delivery cannula with a dehydrated implant positioned within the lumen near the distal opening. [Figure 16D] FIG. 10 is a partial side view of a delivery cannula approaching the anterior canthus. [Figure 17A] 1 shows a pair of implants positioned within the anterior canthus to form a scaffold or reinforced drainage reservoir within the suprachoroidal and / or supraciliary space. [Figure 17B] 1 shows a pair of implants positioned within the anterior canthus to form a scaffold or reinforced drainage reservoir within the suprachoroidal and / or supraciliary space.

[0029] It should be understood that the drawings are illustrative only and are not meant to be to scale. It should be understood that devices described herein may include features that are not necessarily shown in each figure. DETAILED DESCRIPTION OF THE INVENTION

[0030] Implants, systems, and methods for increasing aqueous humor outflow from the anterior chamber of the eye, as well as devices and systems for forming the implants, are disclosed. As described in detail below, outflow stenting from within the eye using biological, cell-based, or tissue-based materials provides biocompatible enhancement of aqueous humor outflow with improved tolerance and safety over shunts in the art. In exemplary embodiments, biological tissue or biomaterials are harvested or generated in vitro and formed into implants, also referred to herein as biological tissue stents, using a cutting device, also referred to herein as a punching device or cutting tool. In one embodiment, the implant is an elongate body or material with an internal lumen to provide a drainage pathway. In a preferred embodiment, the implant is an elongate body or tissue strip without an internal lumen, configured to maintain a cleft and provide supraciliary body stenting (or stenting at another anatomical location, such as Schlemm's canal or transscleral). Lumen-based devices can be limited by the lumen acting as a conduit for fibrotic obstruction. A stent formed from the tissue is then implanted into the eye via an ab interno delivery route to provide aqueous humor outflow from the anterior chamber. The stents described herein can be used as a microinvasive glaucoma surgery (MIGS) treatment, as an adjunct to phacoemulsification or as a stand-alone treatment for glaucoma.

[0031] The use of terms such as stent, implant, shunt, biomaterial, or tissue is not intended to be limiting to any one structure or material. The implanted structure can, but need not, be of a material that, after placement in the eye, is substantially absorbed into the ocular tissue, and once absorbed, may leave a void where the structure was previously located. Once implanted, the structure may also remain in place for an extended period of time, without substantially eroding or resorbing.

[0032] As described in more detail below, the stents described herein can be made from bio-based materials that do not cause toxic or injurious effects once implanted in a patient.

[0033] The term "biologically derived materials" includes naturally occurring biological materials, synthetic biological materials, and combinations thereof suitable for implantation into the eye. Biologically derived materials include materials that are natural biological structures with a biological arrangement found naturally within a mammalian subject, including organs or organ parts formed from tissues and tissues formed from materials grouped together according to structure and function. Biologically derived materials include tissues such as cornea, sclera, or cartilage tissue, as well as acellular biological matrix tissue. Biologically derived materials include amniotic membrane. Tissues considered herein can include any of a variety of tissues, such as muscle, epithelium, connective tissue, and nervous tissue. Biologically derived materials include tissues from a subject, including tissues, organs, organ parts, and tissue grafts suitable for transplantation, including autograft, allograft, and xenograft materials, harvested from a donor or patient. Biologically derived materials include naturally occurring biological materials, including any material found naturally within a mammalian body. As used herein, biologically derived materials also include materials engineered to have a biological arrangement similar to a natural biological structure. For example, materials can be synthesized using in vitro techniques, such as seeding three-dimensional scaffolds or matrices with appropriate cells, engineered materials, or 3D printed materials to form biostructures 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 hyaluronic acid hydrogel or viscous material, such as GEL-ONE cross-linked hyaluronic acid (Zimmer).

[0034] Biological materials can include naturally occurring biological tissue, including any material found naturally in a mammalian body, that has been minimally manipulated or more than minimally manipulated, such that the processing of the biological tissue does not alter the relevant biological properties of the tissue, in accordance with 21 CFR §1271.3(f) of the U.S. Food and Drug Administration (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).

[0035] The biological materials used to form the implants, sometimes referred to herein as biological tissues or biomaterials, can vary and may be, for example, corneal tissue, sclera tissue, amniotic membrane tissue, cartilage tissue, collagen tissue, or other solid biological tissues. The biological tissues can be hydrophilic or hydrophobic. The biological tissues can include or be impregnated with one or more therapeutic agents for the additional treatment of ocular disease processes.

[0036] The biomaterial can contain or release one or more factors of the biomaterial to provide additional treatment for a disease or condition. For example, the material can be tissue that releases tissue-derived healing factors with anti-fibrotic, anti-inflammatory, anti-angiogenic, etc., for repair and regeneration at or near the implantation site. The material can be whole amniotic membrane that releases one or more regenerative and anti-fibrotic factors that help control inflammation and scarring, including, but not limited to, VEGF (vascular endothelial growth factor), VEGF-R (VEGF receptor), ANG1 (angiopoietin 1), TIMP-1 (collagenase inhibitor), TIMP-2 (collagenase inhibitor), IL-1B (interleukin 1B), PDGF-AA (platelet-derived growth factor), TGFb3 (transforming growth factor beta 3), bFGF (basic fibroblast growth factor), and HGF (hepatocyte growth factor). The amniotic membrane contains both growth-promoting and growth-inhibitory proteins (see, e.g., Clinical Ophthalmology 2019:13, 887-894).

[0037] Amniotic tissue may also be derived from the amniotic sac of the placenta. The tissue can be transplanted using freeze-dried, lyophilized membranes, or other minimal manipulations (see, e.g., SURGRAFT, a dehydrated amniotic membrane sheet, or SURSIGHT, an ocular amniotic membrane allograft, both from Surgenex, Scottsdale, Arizona).

[0038] The amniotic membrane can be used as an implantable bio-elutable scaffold or as an adjunctive treatment with a biostent. The amniotic membrane can also be used alone as a primary treatment. The biostent, alone or with the amniotic membrane provided as an adjunctive treatment, can be implanted in any of a variety of locations, including the suprachoroidal space, supraciliary space, Schlemm's canal, cornea, anterior chamber, posterior chamber, intravitreal, epiretinal, subretinal, or other sites in the eye.

[0039] The biostent material can be used in combination with one or more therapeutic agents so that it can be used to additionally deliver drugs to the eye. In one embodiment, the biological tissue can be embedded with sustained release pellets or impregnated with a therapeutic agent for sustained delivery to the target tissue.

[0040] Non-biological materials include synthetic materials prepared by artificial synthesis, processing, or manufacturing that are biologically compatible but not cell- 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, and polysilane, and organic polymers such as polyethylene, polypropylene, polyvinyl, and polyimide.

[0041] Regardless of the source or type of biomaterial, the material can be cut or perforated into an elongated shape suitable for stent placement and implantation in the eye. This tissue cutting process can occur before or during the surgical implantation process. For example, the formation of implants from biomaterials can occur at a tissue bank or manufacturing facility separate from the operating room where the implants will be implanted in the patient. The implants can be preloaded into implant cartridges and packaged for storage and transport at the manufacturing facility. The implant cartridges preloaded with the implants can be additionally designed to form part of a delivery system, eliminating the need for transfer from the implant cartridge to a separate delivery tool.

[0042] A stent implanted in the eye can have a structure and / or permeability that allows aqueous humor outflow from the anterior chamber when placed in the annular dialysis cleft. The biological material can be minimally processed or minimally manipulated tissue for use in the eye. Minimally processed biological materials do not involve the combination of the material with another item, but can include water, sterilants, preservatives, cryopreservatives, storage agents, and / or pharmaceutical or therapeutic agents. Minimally processed biological materials do not exert systemic effects once implanted and do not rely on the metabolic activity of any living cells for their primary function. The biological material can be minimally manipulated at each step of the preparation and use method so that the inherently relevant properties of biological tissue are maintained. The cut implant can be a structural tissue that physically supports or functions as a barrier or conduit, for example, by at least partially maintaining the ciliary cleft formed in the eye.

[0043] Implants cut from biologically derived materials can be minimally manipulated, such as by compressing, shrinking, folding, rolling, or other types of temporary manipulation of the cut implant, allowing the material to return to its original structure once the compressive or shrinking force is released. Thus, minimal manipulation can temporarily mechanically alter the size or shape of the cut tissue while maintaining the tissue's inherent relevant properties for usefulness for reconstruction, repair, or replacement after release from the mechanical alteration. As an example, the biologically derived material can be sclera cut to an oversized shape relative to the inner diameter of the delivery tube into which the implant will be implanted. Minimal manipulation of the cut implant can include temporarily shrinking the sclera material within the lumen of the delivery shaft so that the cut implant has a tendency to return to its original cut size after implantation in the eye. While the biologically derived material is described herein in the context of being cut into a stent-like implant capable of maintaining a cleft for aqueous humor outflow, other methods are also contemplated herein. For example, biomaterials can be compressed into plugs and then implanted into areas of the eye for other purposes such as stenting, occlusion of traumatic ruptures, hyperfiltering blebs, posterior wall ruptures, and other indications.

[0044] Minimal structural processing of biological tissue (e.g., scleral tissue, corneal tissue, or amniotic membrane) or other biological tissue (crosslinked or uncrosslinked) for implantable intraocular use can include longitudinal perforation into elongated tissue strips having a width less than its length, e.g., a length greater than 2 mm and less than 30 mm, and a thickness of about 0.1 mm to 2.0 mm, and a width of about 0.1 mm to 2.0 mm, prior to loading into a delivery shaft. As described in more detail herein, cutting the biological tissue allows for adjustment of the cut width while simultaneously compressing the biological tissue to a consistent thickness.

[0045] Minimal structural processing of the tissue can adjust the width of the tissue to form an implant with a form factor of an elongated pellet, rod, or strip suitable for insertion into an elongated delivery cannula. The elongated strip can have a length of about 2 mm to 11 mm (e.g., greater than 3 mm) and a width of less than 3 mm or less than 2 mm, e.g., 100 microns to 2000 microns. In addition to length and width, the height (i.e., thickness) of the tissue can also be altered by cutting. A planer can be used to cut the tissue to the appropriate thickness to better fit within the inner diameter of the delivery cannula. The tissue can be planed from 1,500 microns to about 50 microns.

[0046] The cut tissue can be loaded into a delivery channel for loading into a shuttle, such as a nosecone assembly or cartridge, described herein, in a manner that compacts the tissue. Cutting, loading, and transport for delivery can be combined within a single assembly or performed by separate assemblies configured to interface with one another. One or more components of the assemblies described herein can be provided as ready-to-use items. For example, the tissue can be pre-cut and provided within a pre-loaded shuttle assembly or implant cartridge, sold as a ready-to-use component or a partially ready-to-use component coupled with a delivery handpiece, for example. The tissue can be cut and loaded at a location remote from the treatment facility, such as a tissue bank or manufacturing facility. The cut tissue can be stored in a cartridge configured to couple to a delivery tool at the treatment facility as a ready-to-use implant.

[0047] FIG. 1A is a cross-sectional view of a human eye showing the anterior chamber AC, ciliary body CB, sclera S, vitreous cavity VC, lens L, and choroid C of the eye. At least one implant 10 can be positioned at an implantation location within the eye such that at least a first portion of the implant 10 is positioned within or flush with the anterior chamber AC and a second portion of the implant 10 is positioned within tissue, such as the supraciliary and / or suprachoroidal spaces of the eye. The implant 10 is sized and shaped to allow the implant 10 to be positioned in such a configuration. The implant 10 provides or serves as a passageway for the flow of aqueous humor away from the anterior chamber AC (e.g., toward the supraciliary and / or suprachoroidal spaces). In FIG. 1A, the implant 10 is represented schematically as an elongated body relative to a delivery cannula 320. The size and shape of the implant 10 can vary. Additionally, the size and shape of the implant 10 prior to insertion into the delivery cannula 320 can change during insertion into the delivery cannula 320 and can also change after deployment from the delivery cannula 320 (see FIG. 1B).

[0048] Multiple implants 10 can be placed within the eye during a procedure to improve aqueous humor outflow from the anterior chamber. As described in more detail below, one or more pairs of implants 10 can be introduced and positioned adjacent to one another to form a longitudinal gap between them. The pair of implants 10 form a scaffold that opens and supports the ocular tissue, creating a reservoir or reservoir for aqueous humor within the longitudinal gap. A reinforced suprachoroidal drainage reservoir can provide an additional advantage over a single biostent that stents the ciliary body without creating a significant reservoir adjacent to the stent. The creation of a reservoir or reservoir within the suprachoroidal and / or supraciliary space is described in more detail below with respect to Figures 17A-17B.

[0049] The implant 10 can be implanted intraocularly, for example, through a clear corneal incision or a scleral incision. The implant can be deployed to create an opening or cleft for increased outflow communication between the anterior chamber AC and the supraciliary space, between the anterior chamber AC and the suprachoroidal space, between the anterior chamber AC and Schlemm's canal, between the anterior chamber AC and the subconjunctival space, or between any other ocular compartment, tissue, or interface where transscleral, subscleral, or episcleral occlusion, stent placement, and / or tissue reinforcement is clinically indicated. In a preferred embodiment, the implant 10 is implanted with its distal end positioned above the ciliary body and its proximal end positioned flush with or at least partially within the anterior chamber AC to provide a supraciliary cleft. The distal end of the implant 10 can be positioned between other anatomical sites in the eye.

[0050] Glaucoma stenting devices are typically constructed from non-biological or other synthetic materials, such as polyimide, which can cause endothelial tissue damage that can lead to progressive, long-term, and irreversible corneal endothelial loss. The materials described herein can reduce and / or eliminate the risk of such tissue damage while still providing enhanced aqueous humor outflow.

[0051] The implant 10 described herein can be formed from any of a variety of biologically derived materials having permeability and / or structure that allows aqueous humor filtration therethrough. The implant 10 can be formed from biologically derived materials that are harvested, manipulated, grown, or manufactured. The biologically derived materials can be obtained or harvested from a patient or donor. The biologically derived materials can be harvested during surgery or, preferably, pre-operatively, such as from a tissue bank or other manufacturing facility. The biologically derived materials can be synthetic living tissues created using in vitro techniques. The biologically derived materials can be derived from stem cells or bioengineered. The tissues can be generated by in situ cell proliferation or non-cell proliferation. The biologically derived materials can be minimally manipulated and / or retain the original structural properties of tissue.

[0052] In an exemplary embodiment, the implant 10 is made of biological tissue. The biological material may be corneal tissue or non-corneal tissue, such as sclera, collagen, or cartilage tissue. In one embodiment, the biological material may be delaminated corneal stromal tissue, devoid of epithelium and endothelium, which is porous and hydrophilic, allowing for aqueous humor filtration. The biological material may be minimally engineered sclera, retaining its original structural characteristics as tissue. The biological material of the implant 10 may, but need not, integrate into the native anatomical structure of the eye after placement within the eye. The implant may allow the surrounding tissue to form a pathway that remains open for an extended period of time, even after stent absorption. The biological material may not significantly absorb or integrate into the anatomical structure of the eye, allowing the implant 10 to remain implanted for an extended period of time, or indefinitely, as desired.

[0053] The biomaterial need not be derived from the eye (e.g., sclera or corneal tissue). For example, the biomaterial can be amniotic membrane. The amniotic sac surrounding the fetus includes the amnion and chorion, both of which are derived from the inner layer of the placenta. The amniotic membrane is part of the amnion and includes an epithelial cell layer, a basement membrane, and an avascular stromal matrix. The amniotic membrane contains pluripotent cells, highly organized collagen, anti-fibrotic and anti-inflammatory cytokines, immunomodulatory factors, growth factors, and matrix proteins, which can promote ocular healing (Murri et al. Clin. Ophthalmol. (2018) 12:1105-1112). During implantation, the amniotic membrane can act as a spacer or tissue reinforcement or a support for another structural element (e.g., a scleral biostent) while releasing factors useful for tissue repair and regeneration. The amniotic membrane bioabsorbs over a period of at least about 3–4 weeks and up to about 3–6 months. After absorption, a structural signature, reservoir, or channel remains at the implantation site. This structural signature may be located in the suprachoroidal space, supraciliary space, or Schlemm's canal and may help improve aqueous humor outflow from the eye. Structural signatures can be created in other locations for other ocular treatments, such as the anterior chamber, anterior horn, posterior chamber, intravitreal, epiretinal, subretinal, corneal, scleral, or other sites, to treat various other ocular conditions, such as uveitis, endothelial loss, and intraocular inflammation. In this way, implants formed from amniotic membrane can be used to create semi-permanent spacers and also to deliver beneficial diffusible factors from tissue that may be useful for various conditions. Amniotic membrane implants can be implanted alone as a primary treatment or in combination with another biological tissue implant formed from other materials (e.g., sclera) as an adjunctive anti-fibrotic or anti-inflammatory treatment using temporary scaffolding, as described in more detail below. When a biological tissue stent is described herein as being derived from the sclera or another ocular biological tissue, amniotic membrane tissue is also considered.

[0054] As described above, the biological material can be permeable or porous, allowing aqueous humor filtration to adequately control or regulate intraocular pressure. The permeable biological tissues described herein (e.g., sclera, cornea, collagen, amniotic membrane, etc.) are preferred materials. Any biological tissue, even impermeable ones, is considered herein as a potential material for functioning as a structural spacer to keep the cyclodialysis device open. Preferably, the implant material can form gaps through which fluid can flow. The gaps can extend longitudinally along both sides of the stent. When more than one pair of implants are introduced, with each implant positioned adjacent to another to form a longitudinal gap between them, the gaps extending longitudinally along both sides of the stent can expand into an aqueous humor reservoir. The pair of implants forms a scaffold that opens and supports the eye tissue between the implants more widely than can be achieved with a single implant. For example, a second implant can be positioned at least an implant width away from the first implant, forming a corresponding longitudinal gap to function as an aqueous humor filtration reservoir. The implants can be spaced at least about 50 microns and up to about 3,000 microns apart to maintain tissue scaffolding between the implants. If the implant material is permeable, more fluid can pass through the cyclodialysis than if the material were impermeable and fluid passed along the outside of the stent. Thus, the materials contemplated herein do not need to be porous to provide the desired functionality. Functionality can be enhanced by the porosity of the material.

[0055] Generally, biomaterials have a degree of hardness and intraocular durability to maintain outflow from the anterior chamber and are less rigid than non-biologic polyimide shunts used to treat glaucoma (e.g., Alcon's CYPASS). The material may have sufficient structure to function as a spacer to open and support continuous supraciliary outflow. Once implanted within the cyclodialysis device, the material can maintain its structural height or thickness, allowing fluid flow through and around the implant. In some embodiments, the cut implant is minimally manipulated by being compressed or reduced within the delivery shaft, thereby reducing the size and / or shape of the cut implant from a first size to a second, smaller size within the shaft. In other embodiments, the implant is cut from dehydrated tissue, such as with 95% ethyl alcohol or lyophilization. The implant is small in size when dehydrated and expands by at least 50% to up to about 150% upon hydration, such as during deployment within the eye.

[0056] The delivery cannula can be sized and shaped to be inserted through the cornea (such as a self-sealing corneal wound) into the anterior chamber and advanced toward the iridocorneal angle. The delivery cannula can deploy the implant between tissue layers near the angle. Once deployed from the delivery cannula, the implant 10 can begin to return to its original shape and / or size, such as by relaxing from the collapsed configuration if it is contracted within the delivery cannula. If the implant 10 is dehydrated within the delivery cannula, it can expand in size once deployed within the eye due to tissue rehydration. Once implanted, the cut implant can be smaller than or the same as its original shape and / or size. Minimally processed biological tissue can be used to treat glaucoma. Bio-derived implant materials have advantages in biocompatibility, anatomical compatibility, and aqueous humor permeability compared to non-biological materials such as polyimide. Biologically derived implant materials have superior conformability and compliance with the scleral wall and may be less likely to cause erosion / loss of the endothelium and sclera over time and with chronic eye rubbing and blinking.

[0057] As used herein, the term "patch" or "patch of material" refers to a piece of biological material having a size along at least one dimension that is larger than the size of an implant cut from the patch of material and implanted in a subject. In some embodiments, the patch of material can have a first shape, and the implant cut or punched from the patch of material can have a second, different shape. For example, the patch of material can be approximately 7 mm wide x 7 mm long x 0.55 mm thick, and the implant cut from the patch of material can be 0.3 mm to 1.0 mm wide x 7 mm long x 0.55 mm thick. The dimensions of the patch of material and the cut implant can vary. The patch of material before cutting can be approximately 5 mm to 10 mm wide, approximately 5 mm to 10 mm long, and approximately 0.25 mm to 2 mm thick, preferably approximately 0.4 mm to 0.7 mm thick. The implant cut from the patch of material can be approximately 0.3 mm to 2 mm wide, preferably approximately 0.7 mm to 1.0 mm wide. The implant cut from the patch of material can be between about 5 mm and about 10 mm in length. The implant cut from the patch of material can be between 0.25 mm and about 2 mm in thickness. The implant can vary in width from about 550 μm to about 1,000 μm upon implantation and / or exposure to liquid. The implant can expand in size by at least 1.2 times upon deployment in the eye. In other words, the implant upon deployment can be at least 20% larger (1.2 times its original size) than its original size before deployment. Preferably, the implant expands to at least 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, to about 3 times its original size, and any size therebetween. The patch of material and the cut implant each have the same length and thickness, but can have different widths. The patch of material and the cut implant can also have different lengths and thicknesses.For example, a patch of material may have a first thickness and an implant cut from the patch of material may have the same thickness, but upon implantation may expand or be folded or rolled to a different thickness than the patch of material.

[0058] The cut implant need not be rectangular in shape, but can have any of a variety of shapes that provide a particular clinical outcome, such as an angled wedge, or other non-rectangular shape. For example, an implant cut into a "dog bone" shape with enlarged distal and proximal ends can provide additional fixation within the target tissue. The implant can be cut to have a narrow, elongated shape at the leading end and an enlarged posterior end to facilitate insertion, in addition to being fixed at at least one end.

[0059] The shape factor of the cut implant can vary, as described elsewhere herein. For example, the tissue can be amniotic tissue formed into a disk, pellet, plug, or rod shape for implantation into the eye or another location in the body to release healing factors from the tissue and provide structural support for the target implantation location. The size of the shape varies depending on the target implantation location. As an example, the implant can be cut into implants having different shapes, such as a disk of biological material having a diameter of about 5 mm, 8 mm, 10 mm, 11 mm, 12 mm, 14 mm, or up to about 15 mm, to an elongated rod shape having a length of about 1 mm to 7 mm and a width of about 0.5 mm to 4 mm. The implant can be the same thickness as the starting material (e.g., about 0.05 mm to 0.7 mm) or can be planed from a first thickness to a second, thinner thickness. The rod shape can be about 3 mm or less in thickness and about 8 mm or less in length, as described elsewhere herein. The thickness and length vary depending on the implantation location. The implants may be formed from a single tissue type but may be of different shapes or sizes. Differently sized implants may be placed at a target location to achieve a specific combination of structural reinforcement at the target location and, in the case of amniotic tissue, release of healing factors at that site. Combinations of tissue types may be implanted together in any of a variety of combinations to provide the desired reinforcement and / or release of healing factors at the target site. For example, an amniotic membrane stent and a scleral tissue stent may be used in combination, as described in more detail below.

[0060] In some embodiments, the patch of material can be relatively large (e.g., 10 mm x 10 mm), and the implant is cut from the patch into strips having much smaller widths (e.g., between about 1.0 mm and about 1.5 mm). The cut implant is then reduced to a delivery conduit having an internal diameter of about 0.8 mm, such that the width of the implant substantially fills the internal diameter. Even if the implant is not oversized for the conduit and therefore remains unreduced, the implant can substantially fill the internal diameter of the delivery conduit. The implant may be oversized for the internal dimensions of the conduit and can be reduced within the conduit to substantially fill it. The implant in a rehydrated state may be larger than the internal dimensions of the conduit, but in a dehydrated state, it may be smaller than the internal dimensions of the conduit. This allows the implant to easily slide within the conduit before and during the deployment phase, and, once rehydrated in the eye, allows for maximum stent placement after deployment. Furthermore, the dimensions of the cut implant vary depending on the size of the cannula through which the implant will be deployed. For example, the inner diameter of the delivery cannula can be about 300 microns to about 2800 microns, or about 600 microns to about 800 microns. In some embodiments, the delivery cannula is a hypotube having an inner diameter of less than about 900 microns to about 228 microns (about 0.009 inches). The dimensions of the delivery cannula will vary depending on the initial size of the implant and whether the delivery cannula is intended for delivery from inside the eye (ab interno) through the cornea or another delivery route. It may also be desirable to deliver the implants described herein via an ab externo method, such as through a scleral flap. For ab externo delivery, the outer diameter of the cannula can be larger compared to delivery cannulas configured for insertion through a self-sealing corneal incision, which preferably minimizes size. If implant delivery is performed through the anterior chamber via a corneal incision, other approaches are similarly contemplated.In this manner, the implant can be cut or drilled to any of a variety of sizes, depending on whether the implant will be reduced into a delivery conduit and the internal dimensions of that delivery conduit.

[0061] Implants cut from a patch of material can have a width, length, and thickness (sometimes referred to herein as the "height" of the tissue). In one embodiment, the width of an implant cut from a patch of material using a cutting device described herein can be at least 100 microns to about 1500 microns, or 100 microns to 1200 microns, or 100 microns to 900 microns, or 300 microns to 600 microns. Implants cut from a patch of material have a width of at least about 100 microns, and can have widths of 1500 microns to 1400 microns to 1300 microns to 1200 microns to 1100 microns to 1000 microns to 900 microns to 800 microns to 700 microns to 600 microns to 500 microns to 400 microns to 300 microns to 200 microns. The length of an implant cut from a patch of material can vary depending on the location of implantation. In some embodiments, the implant has a length of 1 mm to 10 mm, or more preferably 3 mm to 8 mm. The thickness of the implant cut from the patch of material can be 100 microns to about 1,200 microns, or 150 microns to about 600 microns. In one embodiment, the biological material forming the implant can have a thickness of 100 microns to 5 mm. The thickness of the implant depends on the specific patch of material used. The thickness of the implant can also be engineered by planning the tissue during processing. In this way, tissue can be cut to a specific length and width by drilling, and a specific thickness by planning. The thickness of the implant also depends on whether the implant is folded or rolled during implantation; a patch of material as thin as 250 microns can be cut into the implant, doubling the thickness of the folded implant to about 500 microns upon implantation. The thickness of the implant also depends on the biological material used.For example, scleral or corneal tissue can often be as thick as 600 microns, but shrinks to between about 250 and 400 microns after harvest. Thus, an implant cut from a shrunken patch of corneal tissue may only be 250 microns thick. Implants cut from dehydrated scleral, corneal, or other tissues may be up to about 600 microns thick and up to about 1000 microns thick when hydrated.

[0062] In some embodiments, as described in more detail below, the implant cut from the patch of material is cut to substantially fill the conduit through which it is advanced for delivery. In other embodiments, the implant may be oversized relative to the dimensions of the conduit into which it will be deployed. In this embodiment, the implant can be cut to have a first size that is oversized compared to the inner dimensions of the delivery conduit. The oversized implant can be prepared within the delivery conduit, such as by shrinking or compressing it with a tool, so that the implant assumes a second, smaller size when prepared within the conduit. Upon release from the delivery conduit upon deployment within the eye, the implant can attain a third size that approaches its original first size. The third size is due to the reduced implant relaxing toward its unreduced size. The third size may result from the implant being dehydrated within the delivery cannula and rehydrated by bodily fluids once deployed within the eye.

[0063] In a non-limiting example, the biological tissue implant has dimensions of 0.1 mm to 8 mm in any direction and a thickness of 50 microns to 8 mm. In a non-limiting example, the implant is approximately 6 mm in length, 300 microns to 600 microns in width, and 150 microns to 600 microns in thickness. The cuts can be 1 mm to 8 mm in any direction. In a non-limiting example, the cut tissue has dimensions of 100 microns to 800 microns in width and 1 mm to 10 mm in length. Multiple implants may be delivered to one or more target locations during an implantation procedure.

[0064] Referring now to the drawings, FIG. 2A is a box diagram illustrating an embodiment of a treatment system 100. FIG. 2B illustrates the embodiment of the treatment system 100 of FIG. 2A. The treatment system 100 may include one or more of a drilling system 200 and a delivery system 300. The treatment system 100 may further incorporate a biological tissue material 5, such as biological tissue described elsewhere herein, configured to be shaped by the drilling system 200 or the like for formation into an implant 10. The drilling system 200 may include a cutter or perforator 205. The perforator 205 of the drilling system 200 is configured to cut, process, and shape the biological tissue material 5 into an implant 10 for ocular implantation. The drilling system 200 may further incorporate a loading system 400 configured to hydraulically load the implant 10 into an implant cartridge by applying negative or positive pressure. An embodiment of the loading system 400 may include a container or loading cartridge 405 for holding the implant 10 to be loaded into the cannula 320. The loading system may also include a loader 410, which may be a vacuum source for applying suction or negative pressure through the cannula 320 to load the cut implant 10 into the delivery system 300. The loading system 400 may also incorporate an adapter 409 for coupling the cannula 320 to the loader 410. Once cut, the implant 10 is placed into a loading cartridge 405 for transfer to the delivery system 300 using suction by the loader 410, such as a syringe.

[0065] 2A-2B, the delivery system 300 can include an implant cartridge 305 reversibly coupled to a proximal housing or handpiece 310. The implant cartridge 305 reversibly couples to the proximal handpiece 310 via a coupler at a proximal end of the implant cartridge 305 configured to engage a corresponding coupler at the distal end of the proximal handpiece 310. The implant cartridge 305 includes a nosecone 312 and a shaft projecting distally from the nosecone 312. The shaft can be formed from at least one tubular element or delivery cannula 320 having a distal opening 325 to a lumen 330 of the cannula 320. A loader 410 can be coupled to the implant cartridge 305 for loading the implant 10 into the delivery cannula 320 via an adapter 409. The implant 10 , suspended in liquid within the loading cartridge 405 , is transferred from the loading cartridge 405 to the delivery cannula 320 using the loader 410 , which aspirates the implant 10 into the delivery cannula 320 .

[0066] Figure 3A is a box diagram illustrating an embodiment of system 100 including one or more of drilling system 200, implant cartridge 305, and loading system 400. System 100 can further incorporate a biological tissue material 5, such as biological tissue described elsewhere herein, harvested, such as from a donor, and configured to be shaped, such as by drilling system 200, for formation into implant 10. Figure 3B is a box diagram illustrating an embodiment of a manufacturing process for forming implant 10 from biological tissue material 5 and loading implant 10 into a cartridge that can be packaged for storage and transport using system 100 of Figure 3A.

[0067] 3A , the drilling system 200 can include a perforator 205. The perforator 205 of the drilling system 200 is configured to cut, shape, and form the tissue material 5 into an implant 10 for ocular implantation. The drilling system 200 can further incorporate a planer 220 configured to vary the thickness of the tissue material 5.

[0068] The implant cartridge 305 can include a nosecone 312 having a delivery cannula 320 at a distal end and a proximal end region 315. The proximal end region 315 of the nosecone 312 is configured to couple to the handpiece 310, and the distal end region of the shaft protruding distally from the nosecone 312 is configured for insertion into a treatment location on a patient. The delivery cannula 320 has a lumen 330 (see FIG. 7F ) and a distal opening 325 to the lumen 330. The implant cartridge 305 is configured to hold the implant 10 therein for storage and transport from a manufacturing facility to a treatment facility, such as an operating room.

[0069] 3A , the loading system 400 can include a loading cartridge 405 configured to engage a loader 410 to hydraulically load the cut implant 10 into the implant cartridge 305. The implant 10 can be suspended in liquid within the loading cartridge 405 of the loading system 400 and is transferred from the loading cartridge 405 to the delivery cannula 320 using the loader 410 to inject (or aspirate) the implant 10 into the delivery cannula 320. The loader 410 can apply positive pressure to inject the implant 10 or utilize negative pressure to aspirate the implant 10 through the distal opening 325 of the cannula lumen 330.

[0070] The implant cartridge 305, with the implant 10 loaded within the delivery cannula 320, can be removed from the loading system 400 and packaged for storage and transport, such as to a treatment facility, where it will be coupled with a delivery handpiece and used in a surgical procedure. The implant cartridge 305 can be packaged within a packaging 500 that includes one or more specific features intended to prevent the implant 10 contained within the implant cartridge 305 from being damaged or separated from the implant cartridge 305, including one or more physical barriers configured to keep a wet implant 10 moist or a dry implant 10 dry during storage and / or to prevent the implant 10 from being removed from the cartridge 10 within the packaging 500. The packaging 500 can be a radiation-stable container.

[0071] During surgery, the implant cartridge 305, having the implant 10 already loaded within the delivery cannula 320, is reversibly attached to the proximal handpiece 310 via a coupling feature at the proximal end region 315 of the implant cartridge 305 that is configured to engage with a corresponding coupler 317 at the distal end of the proximal handpiece 310, thereby forming the delivery system 300. The delivery system 300 is used to deploy the pre-loaded implant 10 within the eye for repair in anatomical reinforcement, stenting, occlusion, engagement, and aqueous humor drainage procedures.

[0072] Each of the components will now be described in more detail.

[0073] FIG. 3B illustrates an example manufacturing process 600 for forming an implant and packaging it for use in a treatment center. A donor glove received at a tissue bank (box 605) can be used to harvest a patch of material (box 610) having a specific width, length, and thickness. The patch of material can be scleral tissue harvested from the limbus toward the posterior pole, approximately 5 mm to 10 mm. The patch of material can be cut into a ring of material. The patch of material can be lyophilized or left wet. In some embodiments, the thickness (or tissue height) of the patch of material is altered by planing (box 612). Optionally, the starting thickness can be measured (box 614) before the patch of material is planed to the desired thickness. Measurements can be made using a pachymetry device or a mechanical or electronic pachymeter. The patch of material does not need to be planed or measured. Preferably, the thickness is within approximately 50 microns of the inner diameter of the cannula into which the implant will be loaded. If the implant is too thick, the loading process will fail. Therefore, to improve yield, the patch of material is ground down to approximately 800 microns, a size that is universally accepted by most cannulas used in the procedure. The patch of material can then be perforated (Box 615) into strips of the desired width to form the implant. The perforator, as described in more detail below, can be a dual-blade perforator that forms a single strip, or a multi-blade perforator that forms multiple strips. The blade can be angled, for example, at an angle of about 0 degrees to about 25 degrees relative to the blade bevel. The implant, which can be an elongated tissue strip approximately 5 mm to 10 mm in length, can then be loaded into the implant cartridge (Box 620). The implant can be loaded into the cannula of the implant cartridge by suction, injection, or physically pushing the implant with a pusher or another tool. The implant-loaded implant cartridge can then be packaged for storage and transport (Box 625).For example, implant cartridges can be packaged in vapor-barrier pouches or trays. If the implant is wet, fluid can be added to the packaging to maintain a moist environment. If the implant is dry, the vapor-barrier pouch can maintain a dry environment. The systems and tools used to drill, plan, load, and package the implants can be single-use disposable tools or can be autoclaved / cleaned and reused.

[0074] Drilling System 4A-4F illustrate components that make up an embodiment of the perforation system 200, including a perforator 205 and, optionally, a planer 220, as shown in FIGS. 5A-5F. FIGS. 6A-6C illustrate another example of the perforator 205 of the perforation system 200. The configuration of the perforator 205 can vary as described herein and can include any one of the various cutters described in U.S. Pat. No. 10,695,218, U.S. Patent Application Publication No. 2021 / 0361484, and U.S. Patent Application Publication No. 2023 / 0000680, each of which is incorporated herein by reference. In some embodiments, a single implant is formed with each cutting action of the perforator 205, which may include a single blade that forms a single elongated tissue strip or a pair of blades that form a single elongated tissue strip. In other embodiments, multiple implants are formed with each cutting action of the perforator 205. The perforator 205 can incorporate multiple blades or pairs of blades, each of which can form elongated tissue strips that can be loaded into implant cartridges for storage and distribution. Forming multiple implants with a single cutting action of the perforator 205 can be useful, for example, for manufacturing facilities or tissue banks seeking to increase implant production.

[0075] 5A-5C and 5D-5F illustrate an embodiment of a scraper 220 that can be incorporated into the drilling system 200 to modify the thickness of the material 5 and reduce its width into a narrow strip prior to drilling. The material 5 can be cut to the appropriate thickness to better fit within the inner diameter of the delivery cannula 320. FIG. 5A is a schematic diagram of an embodiment of the planer 220 of the drilling system 200 incorporating a blade 222 on a blade carriage 224. The blade 222 can be positioned so that the grinding angle of the blade 222 is coplanar, and the grinding angle can be between about 0 degrees and about 25 degrees. FIG. 5B is a schematic diagram illustrating an exemplary blade shape for the blade 222 of the planer 220 of FIG. 5A, showing a single grind with an angle of about 25 degrees on the left and a double grind with an angle of about 13 degrees on the right. The shape can also include a triple grind of about 6 degrees. The material 5 to be abraded can be frozen onto the barrel 226 or potted in a biocompatible material such as wax or glue. An adjuster 228, such as a screw, can be positioned below the barrel 226 to adjust the level of the material 5, and thus the thickness achieved by the blade 222, as the material 5 passes over the barrel 226 on the blade carriage 224. Figure 5C is a schematic diagram showing the material 5 being abraded. The material 5 can be a portion of the sclera having a total thickness of approximately 1000 to 1200 microns, with the underlying retinal tissue accounting for approximately 25 microns of the total thickness. The upper surface of the material 5 (i.e., away from the retina) is exposed above the surface of the barrel 226 and is abraded by the blade 222 to form a cross-section of scleral tissue approximately 500 to 800 microns thick.

[0076] 5D-5F are perspective views from different angles of an embodiment of the planer 220 of the drilling system 205. A blade 222 is disposed on a blade carriage 224. A barrel 226 is adjustably disposed relative to the blade 222 on the blade carriage 224. The curvature of the barrel 226 can mimic the natural curvature of the material, which may be sclera, to help hold the material flush with the shape of the barrel 226. The material 5 can be held by the barrel 226 using one or more mounting screws 229. As the barrel 226 rotates relative to the blade 222, the material 5 comes into contact with the blade 222, thereby scraping away the upper exposed segment of the material 5. The material 5 being planed can be held around the periphery of the barrel 226 by a clamp or the like. As the material 5 rotates and passes the blade 222, the portion above the height of the blade is cut away, and the material 5 having the desired thickness is held within the clamp of the barrel 226.

[0077] The material 5 can be perforated into elongated strips. While this step is optional, the material 5 may be perforated after it has been cut to the desired thickness using a planer. Referring again to FIGS. 4A-4F , the perforator 205 can include a handle 202 coupled to a plurality of blades 203 at its distal end. The handle does not need to be actually held by a user and can be replaced with various mechanical or electromechanical configurations that allow for control of the force and cutting action. The plurality of blades 203 can include at least a first pair of blades 203 spaced apart from one another to cut the biological tissue 5 with a single cutting actuation along two dimensions. The blades 203 can be spaced apart at an angle that accounts for the bevel of the blades 203, so that the interior spaces between the blades where they penetrate the tissue remain relatively straight and parallel to one another. For example, each blade 203 of an adjacent pair can be angled, e.g., between 0 and 25 degrees relative to the blade bevel, so that the portions of the blades 203 that initially penetrate the tissue are parallel to each other and avoid "squashing" the tissue in the space between them. The blades 203 of the perforators 205 can be parallel to each other (see FIG. 4B) or non-parallel to shape the tissue into parallel or non-parallel and non-linear shapes.

[0078] Each blade 203 may be circular, with an outer periphery formed at the cutting edge 204 and a central hole 210 configured to receive a pin 212 (see FIG. 4A ). The pin 212, extending through each of the blades 203, engages the distal end of the handle 202 like an axle. FIG. 4E shows the handle 202 with the blades 203 and pin 212 removed. This configuration allows the blades 203 to rotate about the axis A of the pin 212 when the handle 202 is urged axially across the surface of the material to be perforated. The blades 203 can be detached from the handle 202 and replaced for each cutting procedure, while the handle 202 can be reused after sterilization. Alternatively, the entire perforator 205 can be discarded after use, or the entire perforator 205 can be sterilized for reuse.

[0079] The number of blades 203 varies depending on the starting tissue size and the desired implant size. The perforator 205 can include 2, 3, 4, 5, 6, 7, 8, 9, 10, or more blades 203 coupled to the handle 202 so that 1, 2, 3, 4, 5, 6, 7, 8, 9, or more tissue strips are formed with a single cutting motion. The size of the blades 203 similarly varies. In some embodiments, each blade is about 10 mm or more and about 20 mm or less in diameter. The blades can be formed from carbon, stainless steel, tungsten, zirconia ceramic, or another material.

[0080] 4B is an end view showing three blades 203, schematically illustrating the cutting edges 204 around the blades 203 and the pin 212 extending through the central hole 210. Ring shims 217 are placed between the blades 203 to ensure that the faces of the blades 203 remain generally parallel to one another and maintain the space between them. The distance between the cutting edges 204 of adjacent blades 203 corresponds to the width W of the resulting implant. This distance can be between about 0.4 mm and 1.0 mm.

[0081] FIG. 4C is a side view of the blade 203 relative to the handle 202 and base 206, with a patch of material 5 disposed thereon. The blade 203 can rotate about axis A along the direction of arrow B and be urged axially toward the patch of material 5 to be cut. FIG. 4D is another schematic side view of the blade. The perforator 205 can be handheld or powered. If handheld, the user applies a downward force to cause the cut as the perforator 205 is urged across the tissue. In another embodiment, the blade 203 is coupled to a powered wheel. A torsion spring can be incorporated to apply a constant amount of force to re-bias the tissue to be cut against the blade 206. A fixed roller 219 can be incorporated below the base 206 to grip and urge the base 206 backward along arrow C as the blade 203 rotates about axis A in the direction of arrow B.

[0082] The blade 203 need not be circular or rotate around the handle 202. FIG. 4F shows an interrelated embodiment of a perforator 205 in which the blade 203 is rectangular and does not roll or rotate while cutting the material. Like the version shown in FIG. 4A, the blades 203 in this configuration can still be positioned parallel to one another to create multiple elongated strips from the material with a single cutting motion. The blade 203 in the embodiment of FIG. 4F can be biased against the material in an up-and-down or pivoting motion to press through the tissue rather than rolling along it. Whether the blade 203 is biased to rotate axially while being pressed downward through the material or biased straight down without any forward or rotating motion, the blade 203 forms a square cross-section for the cut.

[0083] The perforators 205 may be used with or include a base 206 that provides a bearing surface for the blades 203. The base 206 may be a polymer that provides a soft surface against which the blades 203 can be biased. The polymer may be between Shore 50A and Shore 50D, preferably between about 80 Shore A and 90 Shore A and below (approximately 50D). The polymer may be between Shore 60A and Shore 60D. The flexibility of the bearing surface compensates for Z-axis misalignment between adjacent blades 203. Misalignment is more significant when using circular blades.

[0084] 6A-6C illustrate another example of a perforator 205 configured to form at least one implant 10 in a single cutting motion. The perforator 205 can include a base 206 coupled to a top plate 208. The top plate 208 can include a cutting die having at least one blade (not visible), and the base 206 can include a bearing surface 209. The top plate 208 can incorporate multiple blades such that multiple implants having a desired width are formed upon actuation of the perforator 205. The top plate 208 can rotate about a pivot axis of a hinge 213. The cutting die, along with the top plate 208, moves toward the bearing surface 209 about the hinge 213. The bearing surface 209 of the base 206 is positioned below the position of the blade such that the blade can be biased against the bearing surface 209 upon actuation of the cutter 205. The biological tissue 5 can be positioned on the base 206 against the bearing surface 209 to achieve the desired implant width when the blade cuts the biological tissue 5. The biological tissue 5 can be manually loaded onto the cutter 205, for example, using forceps, and the edges of the biological tissue 5 can be aligned against the cutter ledge 214. Once the biological tissue 5 is in the correct position, the top plate 208 can be lowered onto the biological tissue 5. The top plate 208 can secure and optionally compress the biological tissue 5 against the bearing surface 209 as the blade penetrates the biological tissue 5. The blades can be one or more pairs of blades spaced apart from one another to cut the biological tissue 5 with a single cutting actuation along at least two positions. The blades can be spaced apart at an angle that accounts for the bevel of the blades, so that the interior spaces between the blades where they penetrate the tissue remain relatively straight-facing and parallel to one another. The blade shape and mounting arrangement are described in more detail in U.S. Patent Application No. 17 / 940,380, filed September 8, 2022, which is incorporated herein by reference.

[0085] The blades 203 of the cutter 205 can be parallel (see FIG. 6D) or non-parallel (see FIG. 6E) to each other, allowing the cut tissue to be shaped into parallel, non-parallel, and non-linear shapes. Parallel blades produce rectangular tissue segments with square cross-sections. Non-parallel blades can form wedge-shaped tissue segments. Non-parallel shapes may be advantageous for cannula loading and clinical efficacy. Tissue can be cut into various linear or non-linear shapes using a die-cut punch 201 or a blade similar to a cookie cutter (see FIG. 6F). Figures 6G-6M show various shaped implants 10 cut using the punch 201. The die-cut punch 201 allows tissue to be shaped to improve use for surgical staff or to improve clinical response, including, for example, improved fluid flow, improved cleft retention, and enabling drug transport / delivery. The implant 10 can be cut to form an outer periphery 7 and an inner periphery 8, each of which has one of a variety of shapes. For example, FIG. 6G illustrates an implant 10 having an outer periphery 7 and a corresponding inner periphery 8, resulting in a hollow rod shape with a single central opening 9. FIG. 6M illustrates another implant 10 having an outer periphery 7 and multiple openings 9. In this embodiment, the outer periphery 7 can be any shape as described herein. The implant 10 can be cut with a punch or other cutter, as shown herein, or can be cut to form multiple openings 9, such as by laser cutting. Each of the openings 9 can be defined by a separate or substantially connected inner periphery 8. The openings 9 can be loaded with a material that provides a function to the implant 10 upon deployment at a treatment site. For example, the material loaded within the openings 9 can be a drug or combination of drugs for delivery to the implantation site. The material loaded within the openings 9 can include one or more particles, including solid particles, liquid particles, crystalline particles, droplets, or other forms of therapeutic agents configured to be released from the openings 9 of the implant 10 to treat a condition in a patient.

[0086] The bearing surface 209 is located within the base 206 and can be coupled such that the bearing surface 209 can be removed and replaced as needed without having to discard the entire perforator 205. Similarly, the blade can be removed and replaced as needed. The bearing surface 209 can be coupled to the base 206, and the blade can be coupled to the top plate 208 by one or more fasteners, such as screws, or another type of coupling, such as an interference fit. FIGS. 6A-6B show the top plate 208 in an open configuration relative to the base 206, exposing the bearing surface 209 of the base 206. FIG. 6C shows the top plate 208 rotating about the pivot axis of the hinge 213 from the open configuration to a closed configuration in which the top plate 208 abuts the base 206. The top plate 208 can further include a lever 216 that can be activated by the user to ensure complete cutting of the tissue 10 by the blade without applying excessive pressure that would unnecessarily dull the blade. The lever 216 can be movable relative to the top plate 208 to rotate about a pivot axis (which may be the same as or different from the pivot axis of the hinge 213). A return spring 218 can be disposed around a post 207 on the top surface of the top plate 208 to bias the lever 216 upward. A user can close the top plate 208 by rotating it about the pivot axis. Once the top plate 208 is lowered onto the base 206, the lever 216 can be depressed. This action compresses the return spring 218, applying a certain amount of cutting pressure to the top plate 208 and biasing the top plate 208 toward the tissue 10 on the bearing surface 209 so that the blade completely cuts the tissue. The return spring 218 in this configuration provides a feel that prevents the user from pressing the top plate 208 too hard against the base 206, potentially damaging the cutting edge of the blade against the bearing surface 209. The action of lever 216 against top plate 208 provides some feedback to the user that the end of travel of top plate 208 has been reached to prevent inadvertent damage to the blade during cutting.

[0087] In some embodiments, materials are cut by a system that does not incorporate a mechanical blade to cut the material. A laser microtome can be used to planarize materials to change their thickness or height and / or to cut them into long, narrow strips. A laser microtome can cut non-contact using photons. A laser microtome can incorporate a femtosecond laser emitting light in the near-infrared range to make linear cuts. The laser beam can be tightly focused toward the material to be cut using lenses and other optical components. Depending on the source of the material to be cut (e.g., sclera, amniotic membrane, or acellular biomatrix material), the wavelength can be 1030 nm, the pulse duration can be approximately 300 fs, and the pulse repetition rate can be approximately 10 MHz. The material to be cut can be held stationary prior to cutting to ensure a square edge is formed, or it can be cut without the application of any mechanical force. The material to be cut can be held as described elsewhere herein (e.g., with a flat or cylindrical base), and the laser, rather than a sharp blade, performs the cut.

[0088] Loading System Once the material 5 has been cut using the perforator 205, one or more implants 10 can be loaded into the implant cartridge 305 using a loading system 400. FIGS. 7A-7F illustrate a first embodiment of the loading system 400. FIGS. 8A-8F, 9A-9C, and 10A-10B illustrate alternative embodiments of the loading system 400. Generally, the loading system 400 incorporates a loading cartridge 405 configured to hold the perforated implant 10 and a loader 410 configured to transfer the implant from the loading cartridge 405 to the implant cartridge 305. The loader 410 can hydraulically transfer the implant using negative pressure, positive pressure, and / or mechanical pushing.

[0089] 7A shows a loading system 400 including a loader 410 engaged with the cannula 320 of the implant cartridge 305 and a loading cartridge 405 separated from the loader 410. An implant 10 can be manually transferred from the perforator 205 to the loading cartridge 405 and placed in the loader 410. The loader 410 can include a barrel 427 having a plunger 425 extending therethrough and biased to a proximal position relative to the barrel 427 by a spring 435 within the barrel 427. The proximal end of the barrel 427 can have a syringe configuration such that a user can bias the plunger 425 distally to generate positive pressure within the barrel 427. The loader 410 can have a receptacle 440 for the loading cartridge 405 immediately proximal to a receptacle 445 for the implant cartridge 320, such that positive pressure generated within the barrel 427 can be used to push the implant 10 from the loading cartridge 405 into the implant cartridge 320. The loading cartridge receptacle 440 can incorporate a coupling feature 450 configured to reversibly attach the loading cartridge 405 to the barrel 427 of the loader 410. The coupling feature 450 can snap-fit ​​with a corresponding feature on the loading cartridge 405 to align with the implant cartridge receptacle 445. For example, the loading cartridge 405 can be held in place by outer fingers 450 or inner fingers on the cartridge 405 that engage with features in the receptacle 445. The implant cartridge receptacle 445 can include a lumen 455 having a first end 456 with a first opening 458 sized to receive the delivery cannula 320 (see FIG. 7B). A second end 457 of the lumen 455 is configured to align with and be in fluid communication with the loaded cartridge 405 upon installation of the cartridge 405 in the loader 410 (see FIG. 7E). The receptacle 445 for the delivery cannula 320 can be configured to hold the cannula 320.At least a portion of receptacle 445 may include a c-shaped locking feature near first end 456 of lumen 455 sized to receive the outer diameter of cannula 320 (see FIG. 7B). Receptacle 445, including the c-shaped locking feature, may be formed of a relatively soft material to avoid damaging the distal tip of the cannula.

[0090] FIG. 7C is a perspective view of a loading cartridge 405 having a small reservoir 417 in fluid communication with a loading channel 419 within the loading cartridge 405. The reservoir 417 can be positioned more proximally relative to the loading channel 419 to receive the plunger 425 of the loader 410. The loading channel 419 can be positioned more distally relative to the reservoir 417 to align with the lumen 455 of the implant cartridge receptacle 445. The reservoir 417 is sized to hold a small amount of fluid, including a viscous material such as a viscoelastic or a non-viscous liquid such as saline, when the loading cartridge 405 is coupled to the barrel 427. The volume of the reservoir 417 is sufficient to immerse the implant 10 in liquid (for a wet implant 10). The walls of the reservoir 417 can be rounded, forming segments of a sphere, avoiding square edges that could drive the implant 10 against the walls. In some embodiments, the reservoir 417 can be angled so that the deepest portion of the reservoir 417 is shaped to align with the channel 419 and to facilitate alignment of the implant 10 relative to the channel 419. The reservoir 417 is in fluid communication with the loading channel 419. The loading channel 419 can be a narrow, elongated channel extending from the reservoir 417 a distance between a first end 421 and a second end 423 of the channel 419. The first end 421 can be spaced apart from the reservoir 417, and the second end 423 can open into the reservoir 417. The loading channel 419 is axially aligned with and in fluid communication with a lumen 455 of a cannula receptacle 445 sized to receive at least a distal end region of the delivery cannula 320. 7E shows the first end 421 of the loading channel 419 aligned with the second end 457 of the lumen 455 in the cannula receptacle 445. The lumen 455 guides the distal opening 325 of the delivery cannula 320 into alignment with the loading channel 419. The delivery cannula 320 can be inserted through the first end 456 of the lumen 455 until the distal opening 325 of the cannula 320 is aligned adjacent to the longitudinal axis A of the reservoir 417 (see FIGS. 7E-7F).

[0091] The implant 10 can be manually placed into the reservoir 417 of the loading cartridge 405 through the top surface 424 of the loading cartridge 405 (FIGS. 7C-7D). Once the implant 10 is in the reservoir 417, the loading cartridge 405 can be installed into the loading cartridge receptacle 440 of the loader 410. The delivery cannula 320 can be inserted into the lumen 455 of the cannula receptacle 445 either before or after loading the cartridge 405 into the receptacle 440 of the loader 410 and advanced a distance toward the second end 457 of the lumen 455 until the distal opening 325 of the delivery cannula 320 aligns with the reservoir 417 (see FIG. 7E). The plunger 425 of the loader 410 is urged distally toward the loading cartridge 405 until at least a distal end region enters the reservoir 417 of the loading cartridge 405 (FIG. 7E). This creates a positive pressure within the reservoir 417, forcing the implant 10 out of the reservoir 417 and into the loading channel 419. The reservoir 417 of the loading cartridge 405 may have a funnel region 460 configured to screen an overly thick implant 10 from entering the distal opening 325 of the delivery cannula 320 (see FIG. 7D). If the implant 10 becomes wedged within the funnel region 460 of the cartridge 405, the cartridge 405 with the improperly sized wedged implant 10 can be completely removed from the loader 410. A new cartridge 405 holding a new implant 10 can be inserted into the receptacle 440 of the loader 410 without affecting the integrity of the delivery cannula 320 or the loader 410. As the plunger 425 continues distal advancement, the implant 10 enters the distal opening 325 until it is positioned within the lumen 330 of the delivery cannula 320 (see FIG. 7F). A liquid (e.g., a viscous material) in the reservoir 417 can aid in the movement of the implant 10 into the cannula 320.

[0092] Once the implant 10 is fully injected into the cannula tip, the implant cartridge 305 can be removed from the loader 410 for final packaging if loading is occurring at a location away from the treatment facility, such as a manufacturing facility, or if loading is occurring immediately prior to implantation at the treatment facility, the implant cartridge 305 may be immediately installed into the proximal handpiece 310 of the delivery system, as described elsewhere herein.

[0093] 8A-8B illustrate another loading system 400 incorporating a loading cartridge 405 that includes a small reservoir 417 in fluid communication with a loading channel 419. The configuration and form factor of the loading cartridge 405 can vary. FIG. 8A illustrates an embodiment of the loading cartridge 405 that is a plastic tray, with the reservoir 417 and the loading channel 419 molded into the tray area. FIG. 8B illustrates another embodiment of the loading cartridge 405. The reservoir 417 is sized to hold a volume of liquid, such as a viscous material like a viscoelastic or a non-viscous liquid like saline. The reservoir 417 can be pre-filled with liquid before transferring the implant 10 to the reservoir 417. The volume of the reservoir 417 is sufficient to immerse the cut implant 10 in liquid, such that the implant 10 floats within a volume of, for example, approximately 3 mL to 10 mL. The walls of the reservoir 417 can be rounded, forming segments of a sphere to avoid square edges that could drive the implant 10 against the walls. In some embodiments, the reservoir 417 can be angled so that the deepest portion of the reservoir 417 is shaped to align with the channel 419 and facilitate alignment of the implant 10 relative to the channel 419. FIGS. 8C-8F show cross-sectional views of different reservoirs having shapes configured to facilitate loading of the implant 10. FIGS. 8C-8D show the reservoir 417 from a side view and an end view, respectively, with angled sides 428 that meet at the edge of a flat bottom 429. The length and width of the bottom 429, located between the angled sides 428, can vary, but the bottom 429 is preferably slightly longer and slightly wider than the size of the cut implant 10 to be accommodated within the reservoir 417. FIGS. 8E-8F show another embodiment of the reservoir 417 from a side view and an end view, respectively, with curved sides 428. The curved sides 428 can extend entirely around the periphery of the reservoir 417 to form the bottom as well as the sides 428. Alternatively, the curved sides 428 can meet the edges of the flat bottom 429.

[0094] The reservoir 417 is in fluid communication with the loading channel 419. The loading channel 419 can be a narrow, elongated channel extending outward from the reservoir 417 a distance between a first end 421 and a second end 423 of the channel 419. The first end 421 can be spaced apart from the reservoir 417, and the second end 423 can open into the reservoir 417. The loading channel 419 is sized to receive at least a distal end region of the delivery cannula 320 from the first end 421 and function to guide the delivery cannula 320 toward the reservoir 417. The delivery cannula 320 can be inserted through the first end 421 of the loading channel 419 until the distal opening 325 of the cannula 320 enters the reservoir 417.

[0095] FIG. 8A shows a version of the reservoir 417 and loading channel 419. The tray of the device can incorporate one or more elongated slots 430 to provide the user with confirmation of implant size. For example, the slot 430 can have a first end region 431 having a first width and a second end region 432 having a larger second width. Depending on which portion of the slot 430 the implant 10 fits into, the user can insert the implant into the slot 430 to determine whether the implant width is too small, too large, or within the desired size. Portions of the slot 430 can be labeled to indicate their size. The device need not incorporate a slot to confirm implant size. Size confirmation can also be provided by one or more markings or indentations 433 on the top surface of the tray so that the width or length of the implant can be measured and / or confirmed prior to loading.

[0096] FIG. 8B shows a channel 419 extending through the top surface 424 of the loading cartridge 405. The distal end region of the delivery cannula 320 can be inserted into the channel 419 from above so that it slides into the channel 419. The walls of the top surface of the loading cartridge 405 can be chamfered. This protects the distal tip of the delivery cannula 320 as it finds an opening into the first end 421 of the channel 419 without risk of injury. Once the delivery cannula 320 is inserted into the channel 419, the delivery cannula 320 can be advanced a distance toward the second end 423 of the channel 419 until the distal opening 325 of the delivery cannula 320 enters the reservoir 417 through the second end 423 (see FIG. 9C).

[0097] 8B shows implant 10 suspended in the liquid of reservoir 417. Implant 10 is preferably positioned so that it is aligned generally parallel to the longitudinal axis of loading channel 419. This allows the end of implant 10 to be captured within distal opening 325 of cannula 320 as suction is applied through the lumen of cannula 320, thereby drawing implant 10 into lumen 330.

[0098] A vacuum can be applied through the lumen of the cannula 320, and a loader 409, such as a syringe, can be used to aspirate the implant 10 into the lumen 330. FIG. 9A shows an implant cartridge 305 having a delivery cannula 320 at the distal end of the nosecone 312 and a coupler at the proximal end region 315 of the nosecone 312. The coupler is configured to mount the implant cartridge 305 to the proximal handle 310 of the delivery system. The coupler can also be used to engage the delivery cannula 320 with the loader 410. An adapter 409 can be used to couple the implant cartridge 305 to the loader 410. For example, the vacuum source can be a syringe having a luer 426. A first end 411 of the adapter 409 can be attached to the luer 426, and a second, opposite end 412 of the adapter 409 can be attached to the coupler of the implant cartridge 305. The first end 411 of the adapter 409 can have any of a variety of configurations for coupling to a corresponding coupler on a vacuum source, such as threads or other connectors suitable for coupling, and the second end 412 of the adapter 409 can incorporate a bayonet-type coupling feature configured to receive a corresponding coupler on the implant cartridge 305, which is described in more detail below.

[0099] Once the implant cartridge 305 and loader 410 are coupled together by the adapter 409, the loader 410 can be actuated to draw a vacuum through the lumen of the cannula 320. For example, the syringe plunger 425 can be drawn through the syringe barrel 427 to draw a vacuum through the lumen 330 of the delivery cannula 320 (see FIG. 9B ). The distal opening 325 of the delivery cannula 320 is positioned within the reservoir 417 of the loading cartridge 405 near the location of the implant 10. The vacuum through the lumen 330 draws the implant 10 from within the reservoir 417, through the distal opening 325, and into the lumen 330 of the delivery cannula 320. The liquid (e.g., a viscous material) in the reservoir 417 helps to suspend the implant 10 within the reservoir 417 so that when the syringe plunger 425 is withdrawn, the delivery cannula 320 can be positioned near the implant 10 and draw the implant 10 into the distal opening 325 (Figure 9C).

[0100] Once the implant 10 is fully aspirated into the cannula tip, the implant cartridge 305 can be removed from the adapter 409 for final packaging and / or attachment to the proximal handpiece 310 of the delivery system 300. The loading cartridge 405 can include one or more loading posts 422 sized to fit within the distal opening 325 of the delivery cannula 320. FIG. 8B shows two loading posts 422 disposed on the top surface of the loading cartridge 405. Each loading post 422 can have an outer diameter that substantially matches the inner diameter of the delivery cannula 320 near the distal opening 325 so that the loading post 422 can be received within the lumen 330. The loading posts 422 can have different lengths so that different degrees of compression can be achieved upon insertion of the post into the distal opening. 10A-10B show the distal end region of the delivery cannula 320 with the filler post 422 received within the distal opening 325, positioned so that the post 422 penetrates the lumen. The longer the post 422, the further the post 422 penetrates through the delivery cannula 320. The filler post 422 can be at least about 1 mm long and up to about 3 mm long. The post 422 can function to push the implant further into the lumen, for example, if the implant is not fully aspirated into the lumen. The implant 10 can be contracted within the distal end region of the delivery cannula 320. In some embodiments, the proximal handpiece 310 can include a pusher 335 movable relative to the distal opening 325. In other embodiments, the pusher 335 is inherent to the implant cartridge 305, as described in more detail below. By activating the pusher 335 while the distal opening 325 is positioned over the loading post 422, whether the pusher 335 is positioned within the proximal handpiece 310 or the implant cartridge 305, the implant 10 can be reduced within the distal end region of the delivery cannula 320 while keeping the implant 10 at a distance from the distal opening 325.Any undesirable viscous material is removed from the system, and the implant 10 can be contracted between the post 422 and the pusher 335. By actuating the pusher, which is not on the handpiece 310 or the implant cartridge 305 but is part of a separate loading device, the implant 10 can be contracted within the distal end region of the delivery cannula 320.

[0101] In some embodiments, the implant cartridge 305 can incorporate a portion of a pusher within the lumen 330 of the cannula 320. The implant 10 can be positioned distal to the pusher within the lumen 330. When the implant cartridge 305 is loaded into the proximal handpiece for deployment into a patient, the pusher within the handpiece can engage with the pusher within the cannula 320 to deploy the implant 10, as described elsewhere herein.

[0102] The liquid used to hydraulically load the implant 10 into the delivery cannula 320 can vary, whether by suction or positive pressure injection. Hydraulic loading avoids longitudinal tissue contraction and is less likely to clog compared to mechanical loading, which forces the implant into the lumen. The implant moves with the fluid flow. The pressure generated by the syringe plunger, combined with a liquid interface, whether using vacuum or positive pressure, can overcome friction between the tissue and the cannula 320. The liquid can have a viscosity similar to that of water, including balanced salt solution (BSS). The liquid can also have a viscosity greater than that of water at 20°C, or at least about 1.0016 mPa. The liquid can be an ophthalmic mucosal surgical device (OVD).

[0103] The viscous material can be a biocompatible viscoelastic gel. The biocompatible viscoelastic gel is preferably made of a natural polysaccharide, such as hyaluronic acid or its salt, chondroitin sulfate, keratan, keratan sulfate, heparin, heparin sulfate, alginic acid, cellulose derivatives, chitosan, xanthan, or one of their salts. Such biocompatibility avoids any biological signals that increase inflammation, foreign body reaction, or scar formation processes. The minimum polysaccharide content can be about 0.1% to a maximum of about 20%.

[0104] Ophthalmic viscoelastics are divided into two major classes: dispersed and cohesive. Cohesive viscoelastic materials include HEALON (1.4% sodium hyaluronate, 5 × 10 6 Dalton), Healon® 5 (sodium hyaluronate 2.3%, 4 x 10 6 Dalton), HealonGV (registered trademark) (2 x 10 6 Examples of dispersion-type viscoelastic materials include VISCOAT (3% sodium hyaluronate, 5 × 10 5 Dalton), OcuCoat®, and Celoftal® (hydroxypropyl methylcellulose 2.0%), DisCoVisc® (sodium hyaluronate 1.6%, 1.7 × 10 6 Dalton-chondroitin sulfate 4%), Provisc® (sodium hyaluronate 1%, 1.9 × 10 6 Dalton), Amvisc Plus® (sodium hyaluronate 1.6%, 1.5 x 10 6 Dalton), Opegan® (sodium hyaluronate 1%, 0.6-1.2 x 10 6 Dalton) is mentioned.

[0105] Just as the implant 10 can be injected or aspirated into the distal opening 325 of the delivery cannula 320 for loading, the implant 10 can also be injected or aspirated into the proximal opening 322 (see FIG. 12A ) of the delivery cannula 320 for loading. The opening 322 to the proximal end of the delivery cannula 320 can be positioned relative to the implant 10 such that upon application of negative pressure from the distal end of the cannula 320, the implant enters the lumen 330 and moves toward the distal end region of the cannula 320. Alternatively, positive pressure from the proximal end of the cannula 320 can move the implant toward the distal end region of the cannula 320 near the distal opening 325. The implant 10 can be mechanically urged through at least a portion of the cannula 320 using a pusher in combination with negative or positive pressure. Injecting or aspirating the implant into the cannula 320 from the proximal end to the distal end ensures that the implant is fully contained within the lumen and is not at risk of becoming dislodged prior to delivery, for example, during storage and / or transportation of the pre-loaded cannula 320. Loading the implant 10 from the proximal end also allows for precise positioning between the cannula 320 and the loading mechanism.

[0106] Proximal end loading can be accomplished using injection or suction, as described above. The advantage of applying positive pressure is that there is no limit to the force that can be applied, unlike suction, where the force applied to move tissue is actually limited by air in the system, which may expand when a vacuum is applied. The positive pressure and fluid flow using a syringe to push the implant 10 forward through the delivery cannula 320 allows the user to potentially apply much more force than would be possible with a suction-loaded system that has at least some air inside.

[0107] Once placed within the implant cartridge 305, the implant cartridge 305 containing the implant 10 can be packaged for storage and transport, as described in more detail below. The implant cartridge 305 may be installed in the delivery system handpiece 310 without packaging if loading is performed at the treatment facility immediately prior to surgery.

[0108] 11A-11C illustrate an embodiment of packaging 500 for an implant cartridge 320. The implant cartridge 305 can be contained within packaging 500 that includes one or more specific features intended to prevent the implant 10 contained within the implant cartridge 305 from being damaged or separated from the implant cartridge 305. The packaging 500 can include one or more physical barriers, such as a vapor barrier 505, configured to maintain a wet implant 10 moist or a dry implant 10 dry during storage. FIG. 11A illustrates packaging 500 that includes a vial 515 sized to receive a preloaded implant cartridge 305 and a lid 517 sized to close the vial 515. FIG. 11B illustrates packaging 500 for a preloaded implant cartridge 305 that includes a compartment tray 520 having a recess 525 sized to receive one or more components of the implant cartridge 305 to secure the cartridge 305 to the tray 520. The vial 515 and tray 520 can each be further packaged within a pouch or vapor barrier 505 (see FIG. 11C ). Fluid can be added to the tray 520 to maintain a shelf life before sealing the interior of the vapor barrier 505. In some embodiments, as shown in FIG. 11C , the delivery cannula 320 can include a distal plug 510 configured to prevent the implant 10 from being removed from the cartridge 10 within the packaging 500. The distal plug 510 can be a protective silicone sock or impermeable membrane configured to cover the opening from the lumen to prevent fluid loss. The plug 510 can be received over the outer diameter of the distal end region of the cannula 320, as shown in FIG. 11C . The plug 510 can be sized to cover the distal opening 325 and at least a portion of the distal end region of the cannula 320. The plug 510 can be manually removed by the user prior to deploying the implant 10 in the eye to expose the distal opening 325. In other embodiments, the plug 510 can be positioned inside the cannula 320, such as within the lumen 330 distal to the implant 10, and does not need to be removed prior to deployment of the implant 10.In this embodiment, the plug 510 can prevent inadvertent removal of the implant 10 from the cannula, such as during storage and / or transport, but still allow the implant 10 to be deployed from the lumen 330 through the plug 510 if desired.

[0109] The material can vary, but is preferably a relatively soft material that can self-secure to the cannula, such as a flexible polymeric material, including silicone polymer materials. The plug 510 is structured to effectively seal the distal opening 325 fluid-tight and is preferably anhydrous so as not to impart or transfer water (vapor) to the implant 10. The plug 510 in this embodiment, which seals the distal opening 325 from within the lumen 330, can be formed from a material that is acceptable within the eye. The plug 510 can be made of a rapidly bioerodible or biodegradable material, including, by way of example and without limitation, those selected from poly(esters) based on polylactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), and copolymers thereof, as well as poly(hydroxyalkanoates) of the PHB-PHV class, additional poly(esters), and other synthetic and natural polymers engineered to be rapidly biodegradable, among others. In some embodiments, materials that are compatible with the eye and chitosan, such as poly(saccharides), eg, starch, cellulose, cellulose derivatives, or cellulose derivatives such as HPMC, can form the plug material.

[0110] The plug 510 can be inserted into the cannula lumen 330 in a "cork-like" manner, or the plug 510 can fit into the distal end region of the cannula 320 in a "cap-like" manner. The plug 510 can seal the opening 325 from the lumen 330, although there need not be a physical barrier to prevent inadvertent displacement of the implant from the lumen 330.

[0111] The packaging 500 may be radiation stable so that the entire package can be sterilized after the implants 10 are loaded into the cannula of the implant cartridge 305 and packaged as described above.

[0112] Delivery System In addition to being a container for holding pre-loaded implants 10 for storage and transportation from a manufacturing facility to a treatment facility, the implant cartridge 305 (see FIG. 12A, 13A, or 14A) can form part of an ocular stent delivery system 300 (see FIGS. 12C, 13C, and 14C) when coupled to a proximal housing or handpiece 310 (see FIG. 12B or 14B), for example, during a surgical procedure. FIGS. 12C, 13C, and 14C show the implant cartridge 305 installed in the proximal handpiece 310. The proximal handpiece 310 can include a housing 314 that is sized and shaped to be held in one hand of a user. The distal end region of the housing 314 is configured to mate with the proximal end region 315 of the implant cartridge 305. The distal end region of the housing 314 can include a coupler 317, which can be a male-female attachment mechanism, such as a bayonet connection. The distal end region of the housing 314 can define a distal opening 370 sized to receive at least the proximal end region of the nosecone 312 (see FIGS. 13A, 14D, and 15A). The attachment between the nosecone 312 of the implant cartridge 305 and the housing 314 of the proximal handpiece 310 can ensure alignment of the lumen 330 of the delivery cannula 320 with internal features of the handpiece 310, such as the pusher 335 if the pusher 335 is native to the handpiece 310, the buttress 374 for the pusher 335 if the pusher 335 is native to the cartridge 305, or any other elements involved in the deployment of the implant 10 from the cartridge 305.

[0113] The handpiece 310 can include an actuation mechanism configured to deploy the implant from the implant cartridge 305. In some embodiments, the actuation mechanism is configured to retract the implant cartridge 305 and cannula 320 relative to the housing 314 and pusher 335, such that the pusher 335 functionally passively moves through the lumen of the cannula 320 to deploy the implant while substantially maintaining its position relative to the housing 314. In other embodiments, the pusher 335 actively moves distally through the cannula 320 to deploy the implant. In yet other embodiments, the pusher 335 actively moves and the cannula 320 actively moves to achieve deployment of the implant 10.

[0114] The actuation mechanism can include one or more actuators 340 located in one or more regions of the handpiece 310. The actuators 340 can be operated with one hand of a user, such as with a thumb or finger. The configuration of the actuators 340 can vary and include one or more of a knob, button, slider, dial, or other type of actuator configured to move one or more components of the handpiece 310, such as the pusher 335. In some embodiments, the handpiece 310 can include a pusher 335 configured to be slidably moved distally relative to the handpiece 310 by the actuator 340, while a second actuator 344 can be depressed to retract the nosecone relative to the pusher 335 and deploy the implant 10 from the lumen. When the nosecone 312 of the implant cartridge 305 is installed in the handpiece 310, the pusher 335 can be advanced through at least a region of the lumen 330 of the delivery cannula 320 toward the distal opening 325. The pusher 335 can be sized and shaped to complement the interior dimensions of the delivery cannula 320. For example, if the delivery cannula 320 of the implant cartridge 305 has a rectangular, oval, or circular cross-sectional shape, the pusher 335 can also have a rectangular, oval, or circular cross-section, thereby enabling the pusher 335 to effectively push the implant 10 through the lumen 330 of the cannula 320.

[0115] In embodiments where the pusher 335 is inherent to the handpiece, the pusher 335 can be fully retracted to a proximal position before coupling the implant cartridge 305 with the handpiece 310 so that the pusher 335 does not interfere with loading of the implant cartridge 305. The delivery device 300 can include a single actuator for deploying the implant or multiple actuators 340 for deploying the implant. In some embodiments, the first actuator 340 of the delivery device 300 can be a slider, as shown in FIG. 12C , configured to move the pusher 335 from a first (fully retracted) loaded position to a second (at least partially advanced) ready position. The first loaded position retracts the pusher from the distal end region of the delivery device 300 to allow the implant cartridge 305 to be coupled to the proximal handle 310. Once the implant cartridge 305 is seated and held as shown in FIG. 12C , the pusher 335 can be advanced distally through the lumen 330 of the delivery cannula 320. The second, ready position involves advancing the pusher 335 toward the distal end of the proximal handle 310 to advance the implant 10 through the lumen 330 of the cannula 320. In some embodiments, the pusher 335 can be advanced through the lumen 330 and out the distal opening 325 to deploy the implant 10. In other embodiments, the pusher 335 is advanced to a distal position near the proximal end of the implant within the lumen 330, and the delivery cannula 320 is withdrawn proximally while the pusher 335 remains stationary to deploy the implant 10. The pusher 335 is preferably advanced to the second, ready position before inserting the shaft 320 into the eye.

[0116] The proximal handle 310 can further incorporate a movable guard 342 configured to prevent the user from inadvertently pushing the slider 340 beyond the second, ready position (see FIG. 12C ). The guard 342 can be depressed toward the proximal handle 310, thereby covering the second actuator 344 and preventing inadvertent actuation of the second actuator 344. The guard 342 has a length such that it extends over (or has features that extend into) at least a portion of the slider track 345, thereby blocking the first actuator 340 from further distal movement in addition to blocking the second actuator 344. Once the implant 10 has been advanced to the ready position and is ready to be deployed in the eye, the guard 342 can be rotated out of the way to expose the second actuator 344 and remove the features from the track 345. The first actuator 340 is free to slide further distally along the track 345, and the second actuator 344 is depressible. The proximal handle 310 may include one or more markings 350 intended to provide feedback to the user regarding the position of the pusher 335 through the shaft 320. The advancement of the pusher 335 to one or more positions relative to the housing may also provide tactile feedback to the user, as described elsewhere herein.

[0117] The delivery device 300 need not incorporate a slider as an actuator, and the pusher 335 need not be inherent to the handpiece 310 to deploy the implant 10. For example, the implant 10 can be deployed using an actuation mechanism including a single actuator configured to actuate the carriage 364 to retract relative to the housing 314, which in turn retracts the nosecone 312 and cannula 320 relative to the handpiece 310, causing the pusher 335 within the implant cartridge 305 to move distally through the cannula lumen, thereby pushing the implant 10 stored therein out the distal opening 325.

[0118] 13A-13C illustrate the process of loading an implant cartridge 305 into a handpiece 310 including a carriage 364. FIG. 13A is a side cross-sectional view of the implant cartridge 305 in a loaded position prior to installation in the handpiece 310. FIG. 13B is a side cross-sectional view of the implant cartridge 305 installed in the handpiece 310 in a standby position. FIG. 13C is a side cross-sectional view of the implant cartridge 305 installed in the handpiece 310 in a deployed position. The exterior dimensions of the proximal end region 315 of the cartridge 305 can be sized for insertion through a distal opening 370 at the engagement end of the housing 314 to engage the carriage 364 within the housing 314. Attachment between the cartridge 305 and the handpiece 310 can incorporate at least a quarter turn to ensure a secure connection. The proximal end region 315 of the cartridge 305 can also include a luer taper 355 sized to receive a buttress 374 secured within the distal end region of the housing 314. The buttress 374 can be secured within the region near the distal opening 370 to remain in place throughout actuation of the actuation mechanism and can provide a bearing surface for the proximal end of the pusher 335 within the implant cartridge 305, as described in more detail below. The luer taper 355 can also allow for direct connection of a syringe to load an implant into the implant cartridge 305 using suction pressure, for example, as described elsewhere herein. One or more alignment features 313 on the proximal end region 315 of the implant cartridge 305 can aid in aligning and attaching the cartridge 305 to the handpiece 310. The alignment features 313 can prevent the cartridge 305 from being attached unless the handpiece 310 is in the standby position (FIG. 13B). The alignment feature 313 may be a protrusion extending from the outer surface of the proximal end region 315 of the implant cartridge 305 that is sized and shaped to engage with a corresponding alignment feature 372 on the distal end region of the carriage 364 in the handpiece 310.

[0119] 13A-13C, when the handpiece 310 is in the parked position and the cartridge 364 is advanced to its distal-most position within the housing 314, the user can axially insert the proximal end region 315 of the cartridge 305 into the distal opening 370 of the proximal handpiece 310 and rotate the cartridge 305 into position about the longitudinal axis of the handpiece 310 so that the alignment features 313 of the cartridge 305 engage with corresponding alignment features 372 of the carriage 364. When the handpiece 310 is not in the parked position and the cartridge 364 is not in its distal-most position within the housing 314, the alignment features 372 of the cartridge 364 are positioned deep enough within the handpiece 310 to prevent axial engagement and rotational locking of the cartridge 305. The user can be prevented from pushing the cartridge 305 in far enough so that the alignment features 313, 372 can engage with each other. This can prevent a user from accidentally installing an implant cartridge 305 into a handpiece 310 that is not ready to fire.

[0120] As described above, the handpiece 310 can include an actuation mechanism incorporating one or more actuators 340 configured to be operated by a user's hand to move one or more components of the handpiece 310. In some embodiments, the handpiece 310 can incorporate a spring-loaded actuator 340 to deploy the implant. The spring-loaded deployment actuator 340 has a mechanical advantage, thereby reducing the pushing force required to actuate retraction. The actuation mechanism can include a spring-loaded mechanism. The actuation mechanism can include a compression spring 368 positioned to bias the carriage 364 proximally through the housing 314 (see FIGS. 13A-13C, 14D, and 15A-15B). The carriage 364, located within the housing 314, can include a first end configured to receive the proximal end region 315 of the implant cartridge 305 and a second end opposite the first end. The compression spring 368 engages at least a portion of the second end of the carriage 364. A first end of compression spring 368 can abut against tail pin tube 371, and a second end of compression spring 368 can abut against a bearing surface of carriage 364. Spring 368 is compressible between tail pin tube 371 and the bearing surface of carriage 364. Arming the device for deployment can include pushing tail pin 369 further into its bore 373 at the proximal end of housing 314, thereby pushing carriage 364 distally through housing 314 and compressing spring 368 between tail pin tube 371 and the bearing surface of carriage 364 (see FIGS. 13A-13B, 14D, and 15A). When the actuation mechanism is in the armed state, carriage 364 is in its distal-most position relative to housing 314, spring 368 is compressed, and actuator 340 is ready to be fired to release carriage 364, which is biased proximally by spring 368.

[0121] The actuator 340 can have a first portion 341 connected to a second portion 343 by a hinge 375. The hinge 375 can be fixed to the carriage 364. The first portion 341 can extend outside the housing 314 of the handpiece 310 and can be in the form of a button that a user presses downward (or inward toward the housing 314) to activate the implantable device (see arrow D in FIG. 13C ). The second portion 343 of the actuator 340 is located within the housing of the handpiece 310 and is configured to reversibly engage the carriage 364 in its distal-most position relative to the housing 314 when the actuation mechanism is in the armed state. Upon actuation of the actuation mechanism, as the first portion 341 moves downward, the second portion 343 lifts away from the carriage 364 or toggles upward about the hinge 375, thereby disengaging the second portion 343 from the carriage 364. Upon disengagement, compressed spring 368 is free to expand toward its relaxed state, urging carriage 364 proximally through housing 314 along arrow P (see FIG. 13C). The retraction rate of carriage 364 upon release can be controlled by the return of compressed spring 368 to its relaxed state. Alternatively, the retraction rate of carriage 364 upon release can be controlled by the user, as described in more detail below.

[0122] As described above, because the alignment features 372 of the carriage 364 engage the protrusions 313 of the implant cartridge 305, proximal movement of the carriage 364 retracts the nosecone 312 and cannula 320 proximally relative to the housing 314 of the handpiece 310, deploying the implant 10 located within the lumen of the cannula 320. The nosecone 312 retracts through a distal opening 370 of the housing 314 against a buttress 374 secured within the distal end region of the housing 314, causing the distal end of the buttress 374 to abut against the proximal end of a pusher 335 inherent to the implant cartridge 305. The pusher 335 is at least partially disposed within the lumen 330 of the cannula 320 such that the proximal end of the pusher 335 is located outside the proximal opening 322 of the cannula 320 and is available within the proximal end region of the nosecone 305, such as within the luer region 355. Proximal movement of the nosecone 312 and cannula 320 causes the proximal end of the pusher 335 to abut the distal end of the buttress 374, which more effectively forces the pusher 335 into the cannula lumen 330 as the cannula 320, coupled to the nosecone 312, is retracted over the pusher 335. In other words, the pusher 335 is maintained in a substantially fixed position by the buttress 374 as the cannula 320 is retracted over the pusher 335. The implant 10 can be located in the distal end region 380 of the cannula 320, as described elsewhere herein, and the presence of the pusher 335 pushes the implant 10 out of the lumen and into the eye. To reduce sound and shock during operation, a damping component 362 configured to abut the carriage 364 during retraction can be loaded into the handpiece 310, thereby improving patient comfort. The actuation mechanism is configured to be reloaded for further actuation by clicking the tail pin 369, which upon actuation extends further out of the tail pin tube 371, and the device is re-armed by returning inward through the tail pin tube 371 and compressing the spring 368.

[0123] Figures 14A-14F show an interrelated embodiment of an implant cartridge 305 and a handpiece 310 where a pusher 335 is inherent to the implant cartridge 305. Figure 14A shows the implant cartridge 305 separated from the handpiece 310 shown in Figure 14B. Figure 14C shows the implant cartridge 305 and handpiece 310 assembled to form a delivery system 300. Figure 14D is a cross-sectional view along line DD of the delivery system 300 of Figure 14C equipped for implant deployment. Figure 14E is a cross-sectional view along line EE of the implant cartridge 305 of Figure 14A. Figure 14F is an exploded view of the implant cartridge 305 of Figure 14A.

[0124] The elongate shaft extending from the distal end region of the nosecone 312 of the implant cartridge 305 can include at least one tubular element. As best shown in FIG. 14F , the shaft includes a cannula 320, which is a tubular element having a lumen 330 extending between a proximal opening 322 and a distal opening 323. The cannula 320 can be generally straight, such that the lumen 330 is coaxial with a single longitudinal axis A, and both the proximal opening 322 and the distal opening 323 circumscribe the single longitudinal axis A. The cannula 320 can also incorporate one or more bends or curves.

[0125] The shaft of the implant cartridge 305 can further incorporate an outer tubular member 378 that extends over at least the distal end region of the cannula 320, including the distal opening 323 from the cannula 320, thereby forming the distal end of the elongated shaft. The distal end region of the outer tubular member 378 that protrudes beyond the distal end of the cannula 320 can have a length of about 3 mm to about 7 mm. The outer tubular member 378 can be a polymeric material, such as nylon, or another material that can be translucent or transparent to allow visual inspection of the implant 10 within the internal lumen through the outer tubular member 378. Visualizing the implant 10 through the outer tubular member 378 aids in positioning the implant 10 within the cleft as the implant 10 is deployed from the delivery system 300.

[0126] The outer tube member 378, when present (or the distal end region of the cannula 320 in embodiments without the outer tube member 378) can have a curved distal end region 380 and define a distal opening 325 of the elongate shaft. The proximal end region of the cannula 320 can extend along a longitudinal axis A, and a proximal opening 322 into the cannula 320 can surround the longitudinal axis A. The distal end region of the cannula 320 can also extend along the longitudinal axis A, and a distal opening 323 from the cannula 320 can surround the longitudinal axis A. The proximal end region of the outer tube member 378 can be coaxial with the distal end region of the cannula 320, while the distal end region of the outer tube member 378 can curve or bend away from the longitudinal axis A. Thus, the distal end region of the outer tube member 378 can form the curved distal end region 380 of the shaft. The curved distal end region 380 can be a tangent arc to the proximal end region, with a radius of 10 mm to 20 mm, preferably about 10 mm to 15 mm, or about 12 mm. The distal opening 325, whether formed in the tubular member 378 covering the cannula 320 or in the cannula 320 itself, can be beveled to increase the size of the distal opening 325. The bevel can be about 10 degrees to 45 degrees, preferably about 12 degrees to 16 degrees. The most distal end of the shaft can form a flat surface or can be designed for blunt dissection.

[0127] Cannula 320 can be a generally straight tubular element having a single longitudinal axis A, such that lumen 330 extending through cannula 320 is coaxial with axis A. Cannula 320 can also incorporate a distal end region 380 that curves away from the single longitudinal axis A, as described above. Whether generally straight or with a curved distal end region 380, cannula 320 can incorporate a frictional feature 382 near the proximal end region of cannula 320, which is a curve or bend, or a combination of curves or bends, that redirects the lumen away from the longitudinal axis A of cannula 320 (see FIG. 14F). As best shown in FIG. 14E , the pusher 335 of the delivery system can be inherent to the implant cartridge 305 and extends at least partially into the lumen 330 of the cannula 320 such that a portion of the pusher 335 spans a bend or otherwise spans the location of the friction feature 382. The friction feature 382 creates friction between the pusher 335 and the inner surface of the cannula 320 at the location of the feature 382, ​​preventing the pusher 335 from otherwise being attached to the implant cartridge 305. Thus, the pusher 335 can be retained within the implant cartridge 305 solely by friction with the inner surface of the cannula at the location of the friction feature 382. The friction between the pusher 335 and the cannula 320 can be sufficient to prevent inadvertent movement between the pusher 335 and the cannula 320, for example, during shipping and handling of the implant cartridge 305, until deployment of the implant 10 is desired.

[0128] 14D , the proximal end region 315 of the implant cartridge 305 is inserted into the distal opening 370 of the handpiece 310 such that the alignment features 313, which may include a first alignment feature 313a on an upper surface of the proximal end region 315 of the implant cartridge 305 and a second alignment feature 313b protruding from a lower surface of the proximal end region 315 of the implant cartridge 305, engage with the carriage 364 of the handpiece 310. The first alignment feature 313a can engage with a corresponding feature 372a in the carriage 364, and the second alignment feature 313b can engage with a corresponding feature 372b. The proximal end region of the pusher 335 can extend outside the proximal opening 322 of the cannula 320 of the implant cartridge 305 so that at least the length of the pusher 335 is available within the luer taper 355. A distal end region of pusher 335 can reside within the lumen of the shaft just proximal to implant 10 (e.g., within the lumen of outer tubular member 378 or within lumen 330 of cannula 320) such that at least the length of pusher 335 traverses friction feature 382 within cannula 320. As shown in FIG. 14D , carriage 364 is urged distally through housing 314 by an actuation mechanism as described above. First portion 341 of actuator 340 is urged further upward outside of housing 314, and second portion 343 inside housing 314 engages carriage 364, such as at surface feature 346. Releasing carriage 364 by second portion 343, such as by biasing first portion 341 downward, allows spring 368 to bias carriage 364 proximally through housing 314, thereby retracting nosecone 312 and cannula 320 further into opening 370 of housing 314. As nosecone 312 and cannula 320 retract proximally, the proximal end of pusher 335 within luer taper 355 abuts the distal end of buttress 374 secured within the region of the housing near distal opening 370.As described above, the pusher 335 can be retained within the lumen 330 of the cannula 320 only by friction with the inner surface of the cannula 320 at the bend forming feature 382. The force of the buttress 374 against the proximal end of the pusher 335 as the implant cartridge 305 is retracted is greater than the friction between the pusher 335 and the cannula 320 caused by feature 382. The bearing surface of the buttress 374 abuts the proximal end of the pusher 335, preventing the pusher 335 from moving proximally with the cannula 320. As a result, the pusher 335 traverses the lumen 330 of the cannula 320 (and outer tubular member 378, if present) as the cannula 320 is retracted thereover, deploying the implant 10 from the distal opening 325.

[0129] The feature 382 can have a curvature that is offset from the longitudinal axis A of the cannula 320 to provide sufficient friction to prevent the pusher 335 from inadvertently disengaging during shipping and handling, but can overcome the friction without applying excessive force to the pusher 335 during movement of the carriage 364 by the compression spring 368 when deploying the implant 10.

[0130] In some embodiments, the material of the pusher 335 can be softer than the material of the cannula 320, resulting in the pusher 335 elastically deforming where it traverses the feature 382 of the cannula 320. The pusher 335 can be a generally straight, elongated filament having a single longitudinal axis between its proximal end and its distal end. The pusher 335 can be a uniform diameter element formed from a material such as a polymer (e.g., nylon) or metal, with memory to maintain flexibility and maneuverability around bends without undue friction. When the pusher 335 is positioned within the cannula 320, the region of the pusher 335 spanning the feature 382 can deform away from its longitudinal axis to conform to the curvature of the cannula 320. In other embodiments, the pusher 335 is curved and the cannula 320 is straight, providing the desired friction to maintain the pusher 335 within the cannula 320 until deployment is desired. In yet another embodiment, pusher 335 can have a first cross-sectional shape and cannula 320 can have a second cross-sectional shape different from the first cross-sectional shape to provide friction. For example, pusher 335 can have a non-circular cross-section and cannula 320 can have a circular cross-section such that at least a portion of the outer surface of pusher 335 abuts the inner surface of cannula 320 to provide friction to maintain pusher 335 within cannula 320.

[0131] The actuator 340 can be configured to retract the implant cartridge 305 upon depression of the first portion 341, as shown in FIGS. 13A-13C, where the rate of retraction is controlled by the force of a spring 368 biasing the carriage 364 proximally. Alternatively, the user can control the proximal movement with or without assistance from the compression spring 368. FIGS. 15A-15B show an alternative actuator 340 incorporating a two-stage actuation mechanism configured to allow the user to control the rate of retraction provided by the actuator 340. The actuator 340 can incorporate a first portion 341, which can be in the form of a button, extending outside the housing 314 of the handpiece 310, and a second portion 343 located within the housing 314. The first and second portions 341, 343 of the actuator 340 are coupled to the carriage 364 via a hinge 375. In the other embodiments described above, the first and second portions 341, 343 of the actuator 340 were located on opposite sides of the hinge 375. In this embodiment, the first and second portions 341, 343 of the actuator 340 are on the same side of the hinge 375. A spring 384 can be located below the first portion 341 of the actuator 340, configured to bias the first portion 341 upward. A second portion 343 of the actuator 340, located within the housing 314, is also biased upward. The second portion 343 can have a shape and size to engage with a slot 385 in the inner surface of the housing 314 when in the upward position. When equipped, the spring 384 biases the first portion 341 to its upward position such that the second portion 343 engages with the slot 385. During deployment, the user biases first portion 341 downward (or inward toward the interior of housing 314), compressing spring 384. Second portion 343 of actuator 340 moves downward, away from engagement with slot 385. Carriage 364 is then free to retract proximally through housing 314. As with the other embodiments, compression spring 368 is positioned to urge disengaged carriage 364 proximally through housing 314.If the user simply presses down on the first portion 341 without maintaining any bias on the actuator 340, the spring 368 will retract the carriage 364 through the housing 314. The user can choose to maintain a slight forward bias on the first portion 341 of the actuator 340 to resist the force of the spring 368 holding the carriage 364 in a desired position relative to the housing 314, for example, during the second stage of actuation, until full retraction of the implant cartridge 305 is desired. The second stage of actuation can include the user releasing the forward bias on the first portion 341 of the actuator 340, thereby allowing the actuator 340, which is fixedly coupled to the carriage 364 via the hinge 375, to track proximally until the carrier 364 is fully retracted. The user can control the carriage retraction speed by maintaining at least some force (i.e., a forward bias) on the first portion 341 of the actuator 340 in the distal direction. Alternatively, the user can allow spring 368 to control the carriage retraction rate by releasing any force on actuator 340. The actuation mechanism can be reset, such as by biasing tail pin 369 inward through housing 314, which biases carriage 364 and compresses spring 368 distally until second portion 343 again engages feature 385, thereby arming the device for further deployment.

[0132] How to transplant Generally, the implant 10 can be implanted through a clear corneal or scleral incision formed using a delivery cannula 320, which may include an outer tube member 378 described elsewhere herein. A viewing lens, such as a gonioscopy lens, can be positioned adjacent to the cornea. The viewing lens allows for viewing of interior regions of the eye, such as the scleral spur and junction, from a position in front of the eye. The viewing lens may optionally include one or more guide channels sized to receive the cannula 320. An endoscope can also be used during delivery to aid in visualization. Ultrasound guidance can be used as well, using high-resolution biomicroscopy, OCT, or the like. Alternatively, a miniature endoscope can be inserted into the eye through a separate limbal incision to image the eye during implantation.

[0133] The distal tip of the delivery cannula 320 can penetrate the cornea (or sclera) to access the anterior chamber. At this point, a single incision can be made within the eye, such as within the limbus. In one embodiment, the incision is proximal to the limbus, e.g., flush with the limbus or within 2 mm of the limbus in a clear cornea. The incision can be made using the delivery cannula 320, or a separate cutting device can be used. For example, a knife-tipped device or diamond knife can be used to enter the cornea first. A second device with a spatula-shaped tip can then be advanced over the tip of the knife, with the flat of the spatula positioned to coincide with the incision plane. The spatula-tipped device can be the delivery cannula 320.

[0134] The corneal incision can be of a size sufficient to allow passage of the delivery cannula 320. In one embodiment, the incision is about 1 mm in size. In another embodiment, the incision is about 2.85 mm or less in size. In another embodiment, the incision is about 2.85 mm or less and greater than about 1.5 mm. Incisions up to 2.85 mm have been found to be self-sealing.

[0135] After insertion through the incision, the delivery cannula 320 can be advanced into the anterior chamber along a path that allows delivery of the implant 10 from the anterior chamber to a target location, such as the supraciliary space or the suprachoroidal space. With the shaft positioned for the approach, the delivery cannula 320 can be further advanced into the eye so that the distal-most tip of the delivery cannula 320 penetrates tissue at the canthus, for example, the iris root or ciliary body region or the iris root of the ciliary body near the tissue boundary with the scleral promontory.

[0136] The scleral spur is an anatomical landmark on the wall of the canthus. It is superior to the level of the iris but inferior to the level of the trabecular meshwork. In some eyes, the scleral spur is obscured by and directly behind the pigmented subzone of trabecular meshwork. The delivery cannula 320 can be moved along a path toward the canthus and scleral spur, passing near the scleral spur on its way to the supraciliary space but not necessarily penetrating it during delivery. Rather, the delivery cannula 320 can abut the scleral spur and move downward, incising the tissue boundary between the sclera and the ciliary body, with the incision entry point beginning just below the scleral spur near the iris root or just below the iris root portion of the ciliary body. In another embodiment, the implant delivery path intersects the scleral bony spur.

[0137] The delivery cannula 320 can approach the canthus from the same side of the anterior chamber as the deployment position, so that the delivery cannula 320 does not advance across the iris. Alternatively, the delivery cannula 320 can approach the canthus by crossing the anterior chamber AC and then advancing across the iris and / or anterior chamber toward the opposite canthus. The delivery cannula 320 can approach the canthus along various paths. The delivery cannula 320 does not necessarily cross over the eye or intersect with the central axis of the eye. In other words, the corneal incision and the location where the implant 10 is implanted at the canthus can be in the same quadrant when looking toward the eye along the optical axis. Additionally, the path of the implant 10 from the corneal incision to the canthus should not pass through the centerline of the eye to avoid interference with the pupil.

[0138] The delivery cannula 320 can be continuously advanced into the eye, for example, approximately 6 mm. After the cutting surface of the delivery cannula 320 penetrates, for example, the iris root or iris root portion of the ciliary body CB, the implant 10 mounted within the shaft can follow the curvature of the inner scleral wall to bluntly dissect the boundary between the tissue layers of the scleral spur and the ciliary body CB, thereby extending the distal region of the implant 10 through the supraciliary space and further between the tissue boundary of the sclera and the choroid to form the suprachoroidal space. Once properly positioned, the implant 10 can be released from the delivery cannula 320 as described herein. The implant 10 can be urged distally from the delivery cannula 320, or the delivery cannula 320 can be retracted while the implant 10 remains stationary. Alternatively, the implant can be urged distally as the delivery cannula 320 is retracted. Preferably, the cannula 320 is retracted to deploy the implant 10 which remains substantially stationary relative to the handpiece 310 .

[0139] The cannula 320 can be used to create a cleft between tissue at the location of implantation. The distal end region of the cannula 320 can incorporate one or more visual markers 322 to guide the user regarding the depth of penetration (see FIGS. 16C-16D). A first marker 322 can be placed at the desired minimum penetration depth (e.g., approximately 3 mm from the distal-most tip 321 of the cannula). A second marker 322 can be placed further proximal to the first marker 322 for a desired second maximum penetration depth (e.g., approximately 6 mm from the distal-most tip). Once the user has created the desired cleft and is ready to deliver the implant from the lumen, the pusher 335 can be advanced to its third, forward-most position (with the guard 342 out of the way or otherwise removed from the device or absent). The second actuator 344 can be engaged to expel material from the shaft 320. The second actuator 344 can retract the shaft 320 while the pusher 335 remains stationary, ultimately expelling the implant 10 from the lumen.

[0140] The implant 10 can be deployed from the lumen 330 so that at least a portion of the implant 10 is positioned between tissue layers, for example, in the supraciliary space between the ciliary body tissue and the scleral tissue, or in Schlemm's canal. The implant 10 can be deployed to be positioned within the supraciliary space, with at least a distal region positioned between the ciliary body tissue and the sclera and a proximal end positioned within the supraciliary fissure. When positioned within the supraciliary fissure, the proximal end need not protrude into the anterior chamber. Preferably, the proximal end of the implant 10 is positioned so that it remains flush with the cleft between the ciliary body tissue and the scleral tissue and does not extend into the anterior chamber.

[0141] Once implanted, the implant 10 forms a fluid communication pathway between the anterior chamber and a target pathway (e.g., the supraciliary or suprachoroidal space). As noted above, the implant 10 is not limited to implantation in the suprachoroidal or supraciliary space. The implant 10 can be implanted in other locations that provide fluid communication between the anterior chamber and an intraocular location, such as Schlemm's canal or a subconjunctival location, the retina or subretinal location, the intravitreal or posterior chamber, and other ocular locations. In another embodiment, the implant 10 is implanted to form a fluid communication pathway between the anterior chamber and Schlemm's canal and / or a communication pathway between the anterior chamber and a subconjunctival location. The devices described herein can also be used to deliver implants transscleral from an ab interno approach. The implant 10 that forms a fluid communication pathway can be complemented by additional implants, such as an implant formed from amniotic tissue, which elutes one or more inherent healing factors from the amniotic tissue, thereby providing anti-inflammatory and anti-fibrotic effects at the implantation site. The amniotic tissue can provide a healing effect at the implantation site for a period of time until the amniotic tissue is completely absorbed.

[0142] As described elsewhere herein, the biological material can include tissue such as the sclera or amniotic membrane. The tissue can be cut into implants and then loaded into a delivery cannula. The delivery cannula can serve as a storage container for the cut implant and can be used to place the implant into the eye. The implant can be collapsed within the delivery cannula so that the size of the implant within the lumen is smaller than the cut size of the implant. Once the implant is released into position within the eye, the implant can be expanded in size (see FIGS. 1A-1B). The implant relaxes and returns to its cut dimensions, expanding in size, effectively "stenting" the space into which the implant is deployed. The implant can also be sized relative to the dimensions of the delivery cannula so that loading the implant into the lumen of the delivery cannula does not result in compression or collapse of the implant.

[0143] In some embodiments, the implant can be configured to change shape after deployment due to hydration of the tissue within the eye. The implant can be cut from dehydrated biological tissue, such as dehydrated cornea, dehydrated sclera, or dehydrated amniotic membrane. The dimensions of the cut dehydrated tissue can be smaller than the corresponding hydrated tissue. Narrow cuts allow for smaller delivery cannula dimensions (e.g., smaller inner diameters, such as 200 microns to 300 microns). A smaller cannula causes less trauma to the eye and results in smaller crevices during implantation that can be supported by expansion of the implant as it rehydrates in situ during tissue deployment. The tissue can be dehydrated using 95% ethyl alcohol or can be lyophilized tissue. In some embodiments, the implant 10 is packaged to be immersed in a liquid solution. The implant 10 can be loaded into the delivery cannula 320 using a liquid solution, as described above. In other embodiments, the implant 10 is dehydrated and "dry" loaded into the delivery cannula 320. In some embodiments, tissue can be manually transferred into the cannula using a separate loading tool, such as tweezers or a physical pusher, and inserted directly into the lumen. A dehydrated implant 10 allows the size of the delivery cannula to be kept small, for example, allowing the corneal incision to be kept small. Once the implant 10 is deployed from the delivery cannula 320 into the eye, exposure to bodily fluids rehydrates the implant 10, causing it to swell and expand. The expansion of the implant 10 in the hydrated stent opens the space in which the implant 10 is placed and improves the outflow of aqueous humor through the space.

[0144] FIG. 16A shows a dehydrated implant 10d, and FIG. 16B shows the implant of FIG. 16A after rehydration (i.e., implant 10r). The width W of the dehydrated implant 10d may be approximately 600 μm, while the width W of the rehydrated implant 10r is approximately 1,000 μm. Similar to an expandable stent, the dehydrated implant 10d has a minimized size within the delivery cannula 320 during implantation and a maximized size upon deployment within the eye. FIGS. 16C-16D show the dehydrated implant 10d with minimized external dimensions within the distal end region of the delivery cannula 320. The delivery cannula 320 can be inserted through the same small incision size, but the overall therapeutic effect provided is greater due to the larger stent volume in the suprachoroidal space.

[0145] The inner diameter of the delivery cannula 320 can accommodate an implant 10 having a width of approximately 400 microns or more and 800 microns or less. When the implant 10 is deployed in the eye, the living tissue of the implant 10, upon hydration, can expand to a size that can be approximately 50%-200% larger than its initial dehydrated volume. Upon deployment, the implant 10 can expand by at least 1.2 times, at least 1.3 times, at least 1.4 times, at least 1.5 times, at least 1.6 times, at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times up to about 3 times the implant's original size, and any size in between.

[0146] Multiple implants 10 can be deployed within the eye to aid in aqueous humor outflow from the anterior chamber, including implants 10 configured to expand in size upon deployment. The implants 10 can be formed of the same type of material or different materials. In some embodiments, a first implant 10a is formed of scleral tissue and implanted as a primary biostent, and a second implant 10b is formed of amniotic tissue and implanted as a secondary biostent that acts as an adjunctive therapy adjacent to the primary biostent, such as by releasing one or more healing factors at the implantation site of the first implant 10a.

[0147] Multiple implants can also be implanted within a target site to form a scaffold or reservoir within the target site. Figures 17A-17B show a pair of implants 10a, 10b positioned within the anterior canthus to form a scaffold or reinforced drainage reservoir within the suprachoroidal and / or supraciliary space. Figure 17A shows the pair of implants 10a, 10b positioned side-by-side with a longitudinal space forming a reservoir 12 between them. Figure 17B shows the pair of implants 10a, 10b and the scaffolded reservoir 12 from a proximal end view. The longitudinal space forming the reservoir 12 between the two implants 10a, 10b can be a permanent or semi-permanent reservoir that increases suprachoroidal outflow of aqueous humor from the anterior chamber.

[0148] The first implant 10a can be an elongated segment of scleral tissue or other tissue as described elsewhere herein and can be inserted from a delivery cannula to an anterior aqueous drainage location such that the distal end of the first implant 10a is in fluid communication with the suprachoroidal space and the proximal end of the first implant 10a remains at least partially within the anterior chamber or is flush with the cleft to support it open. The second implant 10b can be an elongated segment of scleral tissue or another tissue such as amniotic membrane that serves as an adjunct to the primary implant 10a and is inserted along a similar trajectory such that the distal end of the second implant 10b is placed in fluid communication with the suprachoroidal space and the proximal end of the second implant 10b is in fluid communication with the anterior chamber (e.g., within the AC or flush with the cleft). The second implant 10b can be delivered using the same delivery cannula 320 loaded at the treatment site, or a different delivery cannula 320 preloaded with the second implant 10b. The second implant 10b can be placed around the eye at a distance from the first implant 10a. The distance between the first and second implants 10a and 10b can vary, but is preferably between about 0.5 mm and 2.0 mm to allow for scaffolding of tissue extending longitudinally between the two implants 10a and 10b. In the case of adjunctive treatment by eluting healing factors from the second implant, this ensures that the factors diffuse to the implant site without significant washout. As an example, at 0.5 mm, each implant is approximately 5 degrees on a 12 mm diameter circle, while at 2 mm apart, it is 20 degrees.

[0149] Biotissue implants are resorbable tissues that can be semi-permanent, creating a scaffold for a limited period of time, such as one to three months. For example, amniotic membrane can be used to create an expandable scaffold within the target site that absorbs after approximately 30 days, leaving a functional, improved outflow (e.g., ciliary cleft or trabecular meshwork / canal) with a more open structure. Amniotic membrane can also be used in addition to one or more scleral biostents at the treatment site to reduce fibrosis by eluting amniotic membrane-derived healing factors that diffuse into and around the implantation site, inhibiting fibrosis and promoting regeneration and healing.

[0150] As an example, a glaucoma patient's eye can be prepped and draped using various techniques. A retrobulbar or sub-Tenon block can be performed under monitored anesthesia care (MAC). A first incision is made in the cornea and viscoelastic is injected to deepen the anterior chamber. A goniolens is applied intraoperatively to the cornea to visualize the angle and, with further dilation, visualize the iris / ciliary root insertion with a microscope and goniolens. A supraciliary incision is made using the microinterventional instruments described herein, for example, using a delivery cannula 320 as shown in Figures 12A-12C, 13A-13C, 14A-14F, or 15A-15B. A suprachoroidal reservoir is formed and mechanically expanded to a depth of at least 4 mm and no more than 5 mm into the pars plana of the supraciliary chamber. A second corneal incision can be made to deliver the biological tissue implant 10a by further expanding and scaffolding the reservoir's sidewalls. A third corneal incision can be made to deliver a second biomaterial implant 10b to the opposite superior ciliary body sidewall to create a scaffold and maintain the reservoir. As described elsewhere herein, the distance between the implants 10a and 10b can vary, but is preferably no greater than approximately 2 mm to maintain scaffolding. Bleeding can be minimized using a tamponade. The reinforced suprachoroidal reservoir 12 between the first implant 10a and the second implant 10b can be visualized and confirmed at the end of the case using gonioscopy. Irrigation / aspiration can be performed to remove any debris or viscoelastic. Antibiotics and steroids can be administered at the end of the case. While the procedure described above involves only two implants paired to form a reservoir between them, the procedure can also include placing three or four implants to create additional reservoir space.

[0151] experiment Example 1: Adjunctive intraocular scaffold provided by amniotic membrane Following phacoemulsification, a 0.5mm x 0.5mm x 5mm perforated scleral allograft primary biostent was implanted in the supraciliary space for intraocular stent placement, scaffolding, and scleral cleft reinforcement. A 0.1mm x 0.5mm x 5mm perforated amniotic membrane supplemental biostent was implanted adjacent to the primary biostent in the supraciliary space for adjunctive therapy with continuous bioelution of regenerated amniotic fluid factor derived from amniotic tissue. The first patient's baseline intraocular pressure (IOP) was 21 mmHg and he was treated with four IOP-lowering medications to maintain this pressure. Three months after implantation, his IOP was 19 mmHg, and he was not required to take any IOP-lowering medications at the 3-month postoperative follow-up. The second patient's baseline IOP was 15 mmHg and he was treated with four IOP-lowering medications to maintain this pressure. Three months after implantation, the IOP was 15 mmHg, and only one IOP-lowering medication was used to maintain this pressure. The third patient's baseline intraocular pressure (IOP) was 28 mmHg, and three IOP-lowering medications were used to maintain this pressure. Three months after implantation, the IOP was 15 mmHg, and only two IOP-lowering medications were used to maintain this pressure. The amniotic membrane was partially or completely resorbed in all patients by 90 days. No patients experienced adverse events, and all patients experienced rapid resolution of postoperative iritis after implantation (i.e., resolution within 2 weeks compared with 4 to 8 weeks postoperatively).

[0152] Various embodiments are described with reference to the drawings. However, certain embodiments may be practiced without one or more of these specific details or in combination with other known methods and configurations. In the description, numerous specific details, such as specific configurations, dimensions, and processes, are set forth to provide a thorough understanding of the embodiments. In other instances, well-known processes and manufacturing techniques are not described in particular detail to avoid unnecessarily obscuring the description. Throughout this specification, references to "an embodiment," "one embodiment," "an embodiment," "one implementation," and the like mean that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment or implementation. Thus, the appearance of phrases such as "an embodiment," "one embodiment," "an implementation," "one implementation," and the like in various places throughout this specification do not necessarily refer to the same embodiment or implementation. Furthermore, particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more embodiments.

[0153] Throughout the description, the use of relative terms may indicate relative positions or directions. For example, "distal" may refer to a first direction away from a reference point. Similarly, "proximal" may refer to a position in a second direction opposite the first direction. The reference point used herein may be the operator, with the terms "proximal" and "distal" referring to the operator using the device. A region of the device closer to the operator may be described herein as "proximal," and a region of the device farther from the operator may be described herein as "distal." Similarly, the terms "proximal" and "distal" may also be used herein to refer to an anatomical location of a patient 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. Thus, a proximal location may refer to a location within the patient closer to the entry point of the device along the insertion path toward the target, and a distal location may refer to a location within the patient farther from the entry point of the device along the insertion path toward the target location. However, such terms are provided to establish a relative frame of reference and are not intended to limit the use or orientation of the device to the specific configurations described in the various embodiments.

[0154] As used herein, the term "about" refers to a range of values ​​including the specified value that one of ordinary skill in the art would consider to be reasonably similar to the specified value. In embodiments, about refers to within a standard deviation using measurements generally accepted in the art. In embodiments, about refers to a range covering + / - 10% of the specified value. In embodiments, about includes the specified value.

[0155] Although the specification contains many specificities, these should not be construed as limitations on the scope of what is or may be claimed, but rather as describing features unique to particular embodiments. Certain features described herein in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, while features may be described above as acting in a particular combination and even initially claimed as such, one or more features from the claimed combination may, in some cases, be excluded from the combination, and the claimed combination may be directed to a subcombination or a variation of the subcombination. Similarly, although operations are depicted in the figures in a particular order, this should not be understood as requiring such operations to be performed in the particular order shown, or in any sequential order, or that all of the illustrated operations be performed, to achieve desirable results. Only some examples and embodiments have been disclosed. Variations, modifications, and enhancements to the described examples and embodiments, as well as other embodiments, may be made based on what is disclosed.

[0156] In the above description and in the claims, phrases such as "at least one" or "one or more" may appear followed by a connective listing of elements or features. The term "and / or" may also appear in listings of two or more elements or features. Such phrases are intended to refer to any of the listed elements or features individually, or any of the listed elements or features in combination with any other listed elements or features, unless otherwise implicitly or explicitly contradicted by the context in which they are used. For example, the phrases "at least one of A and B," "one or more of A and B," and "A and / or B" are intended to mean "A alone, B alone, or with AB," respectively. A similar interpretation is intended for listings containing more than two items. For example, the phrases "at least one of A, B, and C," "one or more of A, B, and C," and "A, B, and / or C" are intended to mean "A alone, B alone, C alone, with AB, with AC, with BC, or with ABC," respectively.

[0157] Use of the term "based on" above and in the claims is intended to mean "based at least in part on," allowing for unrecited features or elements.

[0158] The systems disclosed herein may be packaged together in a single package. The completed package is sterilized using a sterilization method such as ethylene oxide or radiation, labeled, and boxed. Instructions for use may be included in the box or provided via an internet link printed on the label.

Claims

1. 1. A system for treating glaucoma in an eye, the system comprising:

1. A drilling system comprising: a cutter configured to cut a biological tissue material into an implant, the biological tissue material comprising amniotic tissue configured to elute one or more healing factors from the amniotic tissue; a container having a reservoir sized to receive a predetermined volume of liquid; a drilling system comprising: A delivery system comprising: a cartridge having a nosecone with a coupler extending from a proximal end region of the nosecone; a delivery cannula extending from a distal end region of the nosecone, the delivery cannula having a lumen and a distal opening to the lumen; a cartridge comprising: a proximal housing configured to engage the coupler of the cartridge; a delivery system comprising: A system comprising:

2. 2. The system of claim 1, wherein the reservoir is sized to suspend the implant in the volume of liquid such that when the distal opening of the delivery cannula is positioned near the implant within the reservoir and a vacuum is applied through the delivery cannula, the implant is sucked into the distal opening of the delivery cannula.

3. The system of claim 1 , wherein the cartridge is configured to couple to a vacuum source.

4. The system of claim 3 , wherein the vacuum source is configured to draw the implant into the distal opening of the delivery cannula when the vacuum source is coupled to the cartridge and activated.

5. The system of claim 4 , wherein the vacuum source comprises a syringe having a syringe barrel with a luer at a distal end and a plunger disposed within the syringe barrel.

6. 6. The system of claim 5, wherein the piercing system further comprises an adapter having a first end sized and shaped to couple with the luer of the syringe and a second end sized and shaped to receive the coupler of the cartridge.

7. 2. The system of claim 1, wherein the container further comprises a loading channel extending outward from the reservoir, the loading channel having a first end region configured to receive the distal end region of the delivery cannula and a second end in fluid communication with the reservoir.

8. The system of claim 1 , wherein the container further comprises a filler post having an outer diameter sized to be received within the distal opening of the delivery cannula.

9. The system of claim 8 , wherein the proximal housing further comprises a pusher extendable through the lumen of the delivery cannula toward the distal opening.

10. 10. The system of claim 9, wherein the implant is configured to be compressed between the loading post and the pusher of the proximal housing once the implant is loaded into the delivery cannula and the cartridge is coupled to the proximal housing to expel the liquid that entered the delivery cannula during loading.

11. The system of claim 1 , further comprising a second biological tissue material.

12. The system of claim 11 , wherein the second biological tissue material comprises scleral tissue or corneal tissue.

13. The system of claim 1 , wherein the liquid is a viscoelastic or saline solution.

14. The system of claim 1 , wherein the implant is sized to be received within the distal opening.

15. The system of claim 1 , wherein the implant is oversized relative to the lumen of the delivery cannula.

16. 16. The system of claim 15, wherein the larger implant compresses when placed within the lumen of the delivery cannula and expands upon deployment into the eye and ejection from the lumen of the delivery cannula.

17. 1. A system for treating glaucoma, the system comprising: a first implant; a second implant; and a delivery cannula; the first implant comprises dehydrated biological tissue cut to a first width sized to be received within a lumen of the delivery cannula, the first implant being configured to rehydrate upon deployment within the eye at an implant location and expand to a second width greater than the first width to provide scaffolding at the implant location; The system, wherein the second implant comprises amniotic tissue configured to elute one or more healing factors from amniotic tissue near the implant location of the first implant.

18. 1. A method of treating glaucoma in an eye, said method comprising: implanting the dehydrated biological tissue cut into a first implant into a target location in the eye; implanting a second implant comprising amniotic tissue configured to elute one or more healing factors from amniotic tissue near the target location of the first implant; opening the target location of the first implant as the first implant expands from the first size to a larger size upon deployment in the eye; and promoting outflow of aqueous humor from the anterior chamber of the eye; A method comprising:

19. 1. A system for treating an eye comprising tissue stored within a lumen of an elongated cannula, the tissue being amniotic tissue.

20. 20. The system of claim 19, wherein the tissue has a length greater than 3 mm.

21. 21. The system of claim 20, wherein the tissue has an outer dimension of less than 3 mm.

22. 20. The system of claim 19, wherein the tissue has a length of about 2 mm or more and 11 mm or less.

23. 20. The system of claim 19, further comprising an impermeable membrane covering an opening from the lumen of the elongate cannula configured to prevent fluid loss.

24. 20. The system of claim 19, wherein the elongate cannula with the tissue within the lumen is packaged in a radiation-stable container.

25. 20. The system of claim 19, wherein the elongated cannula is straight or curved.

26. 20. The system of claim 19, wherein the elongated cannula further comprises a nosecone having a coupling mechanism at a proximal end of the nosecone, the elongated cannula protruding from a distal end of the nosecone.

27. 27. The system of claim 26, further comprising a handpiece having a distal coupler configured to engage the coupling mechanism on the nosecone to form a delivery system.

28. 28. The system of claim 27, wherein the handpiece is configured to deploy the tissue from the lumen into the eye.

29. 20. The system of claim 19, wherein the elongate cannula comprises a beveled distal tip at its distal opening from the lumen.

30. 20. The system of claim 19, wherein the elongate cannula comprises a hydrophobic or hydrophilic material.

31. A system for treating an eye comprising amniotic tissue processed into an elongated shape having a width of about 100 microns to 2000 microns and configured to elute one or more healing factors derived from the amniotic tissue.

32. 32. The system of claim 31, further comprising a perforator configured to process the amniotic tissue by cutting the amniotic tissue into the elongated shape.

33. 33. The system of claim 32, wherein the perforator comprises a plurality of blades configured to make parallel cuts that form a plurality of strips, each strip having the elongated shape.

34. 34. The system of claim 33, wherein the plurality of blades are circular and configured to rotate relative to the perforator handle.

35. 35. The system of claim 34, wherein the plurality of blades passively rotate as a user moves the perforator along the amniotic tissue.

36. 35. The system of claim 34, wherein the plurality of blades are powered to rotate by a motor.

37. 34. The system of claim 33, wherein the perforator further comprises a base comprising a material having a durometer between Shore 60A and Shore 60D.

38. 34. The system of claim 33, further comprising an implant cartridge comprising an elongate cannula with a lumen extending between a proximal opening and a distal opening.

39. 39. The system of claim 38, further comprising a loader for inserting at least one strip into the lumen of the elongate cannula.

40. 40. The system of claim 39, wherein the loader is positioned relative to the elongated cannula of the implant cartridge to place the at least one strip into the lumen through the distal opening.

41. 41. The system of claim 40, wherein the loader utilizes positive pressure to inject the at least one strip through the distal opening.

42. 41. The system of claim 40, wherein the loader utilizes negative pressure to draw the at least one strip through the distal opening.

43. 1. A system for treating glaucoma in an eye, the system comprising: a first biological tissue material cut into a first implant sized and shaped for intraocular implantation at a target location within the eye; a second biological tissue material cut into a second implant that is the size and shape of an intraocular implant at or near the target location within the eye; Including, the first biological tissue material includes sclera tissue or cornea tissue; the second biological tissue material comprises amniotic tissue configured to elute one or more healing factors from the amniotic tissue near the target location within the eye. system.

44. 44. The system of claim 43, wherein the target location within the eye comprises a suprachoroidal space, a supraciliary space, Schlemm's canal, an anterior chamber, a posterior chamber, an intravitreal, epiretinal, or subretinal location.

45. 44. The system of claim 43, wherein the first implant has an elongated shape with a length of about 3 mm to about 11 mm, a width of about 0.10 mm to about 3 mm, and a thickness of about 0.05 mm to about 1 mm.

46. 46. ​​The system of claim 45, wherein the second implant has an elongated shape with a length of about 3 mm to about 11 mm, a width of about 0.10 mm to about 3 mm, and a thickness of about 0.05 mm to about 1 mm.

47. 1. A system for treating glaucoma in an eye, the system comprising:

1. A drilling system comprising: a cutter configured to cut the biological tissue material into an implant; a container having a reservoir sized to receive a predetermined volume of liquid; a drilling system comprising: A delivery system comprising: a nosecone having a coupler extending from a proximal end region of the nosecone; a delivery cannula extending from a distal end region of the nosecone, the delivery cannula having a lumen and a distal opening to the lumen; a cartridge comprising: a proximal housing configured to engage the coupler of the cartridge; a delivery system comprising: A system comprising:

48. 48. The system of claim 47, wherein the reservoir is sized to suspend the implant in the volume of liquid such that when the distal opening of the delivery cannula is positioned near the implant within the reservoir and a vacuum is applied through the delivery cannula, the implant is sucked into the distal opening of the delivery cannula.

49. 48. The system of claim 47, wherein the cartridge is configured to couple to a vacuum source.

50. 50. The system of claim 49, wherein the vacuum source is configured to draw the implant into the distal opening of the delivery cannula when the vacuum source is coupled to the cartridge and activated.

51. 51. The system of claim 50, wherein the vacuum source comprises a syringe having a syringe barrel with a luer at a distal end and a plunger disposed within the syringe barrel.

52. 52. The system of claim 51, wherein the piercing system further comprises an adapter having a first end sized and shaped to couple with the luer of the syringe and a second end sized and shaped to receive the coupler of the cartridge.

53. 48. The system of claim 47, wherein the container further comprises a loading channel extending outward from the reservoir, the loading channel having a first end region configured to receive the distal end region of the delivery cannula and a second end in fluid communication with the reservoir.

54. 48. The system of claim 47, wherein the container further comprises a filler post having an outer diameter sized to be received within the distal opening of the delivery cannula.

55. 55. The system of claim 54, wherein the proximal housing further comprises a pusher extendable through the lumen of the delivery cannula toward the distal opening.

56. 56. The system of claim 55, wherein the implant is loaded into the delivery cannula once the cartridge is coupled to the proximal housing and compressed between the loading post and the pusher of the proximal housing to expel the liquid that entered the delivery cannula during loading.

57. 48. The system of claim 47, further comprising the biological tissue material.

58. 58. The system of claim 57, wherein the biological tissue material comprises scleral tissue.

59. 48. The system of claim 47, wherein the liquid is a viscoelastic or saline solution.

60. 48. The system of claim 47, wherein the implant is sized to be received within the distal opening.

61. 48. The system of claim 47, wherein the implant is oversized for the lumen of the delivery cannula.

62. 62. The system of claim 61, wherein the larger implant compresses when placed within the lumen of the delivery cannula and expands upon deployment into the eye and ejection from the lumen of the delivery cannula.

63. 1. A system for treating glaucoma, the system including an implant and a delivery cannula, the implant comprising dehydrated biological tissue cut to a first width sized to be received within a lumen of the delivery cannula, the implant configured to rehydrate and expand to a second width greater than the first width upon deployment within the eye.

64. 1. A method of treating glaucoma using dehydrated biological tissue cut into an implant having a first size that expands to a larger size upon deployment within the eye, the larger size of the implant opening a space within the eye to improve outflow of aqueous humor from the anterior chamber.

65. 1. A method of preparing an implant for implantation into an eye of a patient and inserting the implant into the eye of the patient, the method comprising: cutting the patch of material with a cutting member to form the implant from the patch; coupling a cartridge to an aspiration device, the cartridge comprising a nosecone and a delivery cannula extending from a distal end of the nosecone, at least a distal end region of the delivery cannula being sized and shaped for insertion into the anterior chamber of the eye, the delivery cannula comprising a lumen; immersing the distal end region of the delivery cannula into a volume of viscous material containing the implant; aspirating the implant into the lumen of the delivery cannula using the suction device; A method comprising:

66. 66. The method of claim 65, further comprising transferring the cartridge from the suction device to a delivery device, inserting the distal end region of the delivery cannula into the anterior chamber of the eye, positioning the distal end region of the delivery cannula adjacent to ocular tissue, and actuating the delivery device to deploy the implant from the delivery cannula through at least a portion of the lumen such that the implant engages the ocular tissue.

67. 67. The method of claim 66, further comprising delivering the viscous material through the delivery cannula.

68. A system for treating an eye comprising tissue stored within a lumen of an elongated cannula.

69. 69. The system of claim 68, wherein the tissue comprises scleral tissue or acellular biomatrix tissue.

70. 69. The system of claim 68, wherein the tissue has a length greater than 3 mm.

71. 71. The system of claim 70, wherein the tissue has an outer dimension of less than 3 mm.

72. 69. The system of claim 68, wherein the tissue has a length of about 2 mm or more and 11 mm or less.

73. 69. The system of claim 68, further comprising an impermeable membrane covering an opening from the lumen of the elongate cannula configured to prevent fluid loss.

74. 69. The system of claim 68, wherein the elongate cannula with the tissue within the lumen is packaged in a radiation-stable container.

75. 69. The system of claim 68, wherein the elongated cannula is straight or curved.

76. 69. The system of claim 68, wherein the elongated cannula further comprises a nosecone having a coupling mechanism at a proximal end of the nosecone, the elongated cannula protruding from a distal end of the nosecone.

77. 77. The system of claim 76, further comprising a handpiece having a distal coupler configured to engage the coupling mechanism on the nosecone to form a delivery system.

78. 78. The system of claim 77, wherein the handpiece is configured to deploy the tissue from the lumen into the eye.

79. 69. The system of claim 68, wherein the elongate cannula comprises a beveled distal tip at its distal opening from the lumen.

80. 69. The system of claim 68, wherein the elongate cannula comprises a hydrophobic or hydrophilic material.

81. A system for treating an eye comprising scleral tissue processed into an elongated shape having a width of about 100 microns to 2000 microns.

82. 82. The system of claim 81, further comprising a perforator configured to process the scleral tissue by cutting the scleral tissue into the elongated shape.

83. 83. The system of claim 82, wherein the perforator comprises a plurality of blades configured to make parallel cuts that form a plurality of scleral strips, each scleral strip having the elongated shape.

84. 84. The system of claim 83, wherein the plurality of blades are circular and configured to rotate relative to the perforator handle.

85. 85. The system of claim 84, wherein the plurality of blades passively rotate as a user moves the perforator along the scleral tissue.

86. 85. The system of claim 84, wherein the plurality of blades are powered to rotate by a motor.

87. 84. The system of claim 83, wherein the perforator further comprises a base comprising a material having a durometer between Shore 60A and Shore 60D.

88. 84. The system of claim 83, wherein the blade is angled relative to the angled grinding portion of the blade.

89. 83. The system of claim 82, further comprising a planer configured to reduce the height of the scleral tissue.

90. 84. The system of claim 83, further comprising an implant cartridge comprising an elongate cannula with a lumen extending between a proximal opening and a distal opening.

91. 91. The system of claim 90, further comprising a loader for inserting at least one scleral strip into the lumen of the elongate cannula.

92. 92. The system of claim 91, wherein the loader is positioned relative to the elongated cannula of the implant cartridge to place the at least one scleral strip into the lumen through the distal opening.

93. 93. The system of claim 92, wherein the loader utilizes positive pressure to inject the at least one scleral strip through the distal opening.

94. 93. The system of claim 92, wherein the loader utilizes negative pressure to draw the at least one scleral strip through the distal opening.

95. 1. An ocular stent delivery system comprising: an ocular stent; 1. A cartridge containing the ocular stent, said cartridge comprising: a nosecone having a proximal end region and a distal end region; an elongate shaft extending from the distal end region of the nosecone, the elongate shaft comprising a cannula having a lumen extending between a proximal opening and a distal opening, the cannula comprising a curved portion located between the proximal opening and the distal opening; a pusher disposed at least partially within the lumen of the cannula to span the curve, the proximal end of the pusher being located outside the proximal opening of the cannula and within the proximal end region of the nosecone; a cartridge comprising: a proximal handpiece configured to couple with the cartridge, the proximal handpiece comprising: a housing defining a distal opening sized to receive the proximal end region of the nosecone; a carriage located within the housing and configured to be releasably coupled to the proximal end region of the nosecone; an actuation mechanism configured to retract the cartridge relative to the housing such that the pusher deploys the ocular stent through the distal opening; a proximal handpiece comprising:

1. An ocular stent delivery system comprising:

96. 96. The system of claim 95, wherein the actuation mechanism comprises an actuator and a spring.

97. 97. The system of claim 96, wherein the actuator further comprises a first portion, a second portion, and a hinge, the hinge being fixed to the carriage.

98. 98. The system of claim 97, wherein when the actuation mechanism is in a primed state, the carriage is in a distal-most position relative to the housing, the spring is compressed, and the first portion is biased upward.

99. 99. The system of claim 98, wherein the second portion of the actuator is biased downwardly into engagement with the carriage.

100. 99. The system of claim 98, wherein the second portion of the actuator is biased upwardly into engagement with the housing.

101. 99. The system of claim 98, further comprising a buttress secured within a region of the housing near the distal opening, the buttress having a distally facing bearing surface.

102. 102. The system of claim 101, wherein when the cartridge is coupled to the proximal handpiece, the proximal end of the pusher is positioned adjacent the distally facing bearing surface of the buttress.

103. 103. The system of claim 102, wherein actuation of the actuation mechanism moves the carriage proximally through the housing.

104. 104. The system of claim 103, wherein proximal movement of the carriage through the housing retracts the cartridge against the buttress, causing the distally facing bearing surface of the buttress to abut the proximal end of the pusher and prevent the pusher from retracting with the cartridge.

105. 105. The system of claim 104, wherein the pusher is retained within the lumen of the cannula solely by friction between the pusher and an inner surface of the cannula at the bend.

106. 106. The system of claim 105, wherein the spring force is greater than the frictional force between the pusher and the inner surface of the cannula at the curved portion.

107. 105. The system of claim 104, wherein the speed of movement of the carriage is controlled by the spring.

108. 105. The system of claim 104, wherein the speed of movement of the carriage is controllable by a user with the aid of the spring.

109. 96. The system of claim 95, wherein the actuation mechanism is configured to be recharged for multiple actuations.

110. 96. The system of claim 95, wherein the cartridge further comprises an outer tubular member extending across at least the distal opening of the cannula and forming a distal end of the elongate shaft.

111. 111. The system of claim 110, wherein the outer tubular member is translucent or transparent.

112. 111. The system of claim 110, wherein the distal end region of the outer tubular member is curved and defines a distal opening of the elongate shaft.

113. 96. The system of claim 95, wherein the ocular stent is minimally processed biological tissue.

114. 114. The system of claim 113, wherein the minimally processed biological tissue is amniotic tissue or scleral tissue or acellular biological matrix tissue having dimensions sized to be received within the lumen.

115. 115. The system of claim 114, wherein the minimally processed biological tissue is cut to a length of at least about 2 mm and not more than about 11 mm.

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