Support

Abstract

A system for preparing an implant and endoscopic insertion of the implant into an eye includes a handle having one or more actuators and an elongate shaft having an outer sheath and an elongate member located within a lumen of the tubular outer sheath. The system includes a recess sized to hold a sheet of material fixed relative to the handle and a cutting member movable relative to the handle and the recess. The cutting member cuts the sheet of material into an implant as the cutting member moves toward the cutting configuration. Once cut, the implant is axially aligned with the lumen of the tubular outer sheath. The inner elongate member is movable relative to the tubular outer sheath to advance the implant to a deployed position in the lumen of the tubular outer sheath for delivery into the eye. Related apparatus and methods are provided. A stent is also disclosed.

Description

[0001] This application is a divisional application of the PCT international invention patent application with application number 202080057488.5, application date January 30, 2020, and titled "Implantable biological scaffold and system for forming and preparing biomaterials for the treatment of glaucoma".

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of priority under 35 U.S.C. §119(e) to the following co-pending U.S. provisional patent applications: Serial No. 62 / 861,900, filed on June 14, 2019; Serial No. 62 / 897,570, filed on September 9, 2019; and Serial No. 62 / 943,106, filed on December 3, 2019. The disclosures of the provisional applications are incorporated herein by reference in their entirety. Technical Field

[0004] The present application relates to an implantable biological scaffold and a system for forming and preparing biological materials for the treatment of glaucoma. Background Art

[0005] The mainstay of ophthalmic surgery for glaucoma is to enhance aqueous humor outflow. There are multiple approaches to this surgery, including: 1) external trabeculectomy or shunting, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a transscleral outflow pathway; 2) internal trabecular or transscleral outflow stenting or aqueous shunts with hardware-based implantable devices or with ablative, non-implantable cutters such as dual blades and trabeculectomies; and 3) internal epi-parietal stenting using implantable non-biologic hardware implants.

[0006] Current endoscopic stenting devices and methods are based on non-biological hardware materials such as polyimide, polyethersulfone, titanium, polystyrene block-isobutylene block-styrene, etc. Such implantable devices based on non-biological hardware have significant drawbacks because they can cause severe erosion, fibrosis, and ocular tissue damage, such as endothelial cell loss.

[0007] In view of the foregoing, there is a need for improved devices and methods related to ophthalmic surgery for treating glaucoma. Summary of the invention

[0008] Disclosed are methods and devices for reducing, adjusting or otherwise regulating intraocular pressure by implanting a minimally invasive biological tissue scaffold in the eye. In an example embodiment, a biological tissue implant, such as a biological tissue scaffold, a shunt or an implant, is implanted in the eye so that the scaffold is at least partially positioned in the eye at a suprachoroidal, transscleral and / or supraciliary position to treat glaucoma. The scaffold can be implanted in the eye via an intraorbital delivery path using a delivery device configured for such a delivery path. In an example embodiment, the scaffold assists or otherwise provides an uveoscleral outflow pathway for aqueous humor to drain from the anterior chamber to the eye. The scaffold provides a fluid channel between the anterior chamber and the suprachoroidal space and / or supraciliary space. The scaffold provides a fluid channel / outflow in two independent but cooperative ways, such as by scaffolding the supraciliary fissure and by using a hydrophilic biomaterial that allows exudative water to flow through the material itself. Other drainage pathways are also contemplated, including Schlemm's canal or through a subconjunctival position.

[0009] In one aspect, a system for preparing an implant and inserting the implant into an eye is provided. The system includes a handle having one or more actuators; an elongated shaft extending from the handle in a distal direction. The elongated shaft has a tubular outer sheath and an inner elongated member located within the lumen of the tubular outer sheath. The system includes a recess sized to hold a sheet of material fixed relative to the handle and a cutting member movable to a cutting configuration relative to the handle and the recess. When the cutting member moves toward the cutting configuration, the cutting member cuts the sheet of material into an implant. Once the implant is cut, it is axially aligned with the lumen of the tubular outer sheath. The inner elongated member can be moved relative to the tubular outer sheath to advance the implant to a deployment position in the lumen of the tubular outer sheath for delivery into the eye.

[0010] The sheet of material may include a biologically derived material suitable for implantation into the eye. The biologically derived material may include tissue harvested from a donor or eye. The biologically derived material may be an autologous transplant, an allograft, or a xenograft material. The material may be an engineered tissue. The engineered tissue may be a 3D printed material suitable for implantation. The biologically derived material may have a permeable and / or sturdy structure to allow aqueous outflow from the eye when the implant cut from the sheet of material is positioned within the ciliary detachment cleft. The implant cut from the sheet of material may be bioresorbable or non-bioresorbable.

[0011] The implant may include one or more therapeutic agents. The one or more therapeutic agents may include an antiproliferative agent, an antifibrotic agent, an anesthetic, an analgesic, a cell transport / mobility inhibitor, an anti-glaucoma drug, a prostaglandin analog, a carbonic anhydrase inhibitor, a neuroprotectant, an antibiotic, an antiviral agent, an antiallergic agent, an anti-inflammatory agent, a mydriatic agent, or an immunomodulator.

[0012] The sheet of material may be compressed and / or tensioned before the cutting member is moved to the cutting configuration. The sheet of material may be compressed between two juxtaposed planar surfaces to prevent movement during subsequent cutting of the sheet of material with the cutting member. The sheet of material may be tensioned by a pair of flexible tensioner legs configured to apply a tensioning force away from a centerline of the sheet of material.

[0013] The system may also include a box detachably coupled to the area of ​​the handle. The box may include a base and a cover. The recess may be positioned within the base of the box. The recess may be located within the handle. The system may also include an access door coupled to the handle and configured to close the recess when rotated to a closed configuration and to expose the recess when rotated to an open configuration. The access door may be formed of a transparent or translucent material. The system may also include a protrusion extending upward from the centerline of the recess, thereby forming two channels in the recess on both sides of the protrusion. The protrusion may push the centerline of the sheet of material upward toward the door. When the access door is rotated relative to the handle to a closed configuration, the sheet of material may be captured between the protrusion and the access door. The access door may be configured to apply tension to the sheet of material when the access door is in a closed configuration. The access door may include an actuator configured to apply tension. The actuator may include a pair of flexible stretcher legs configured to extend into the recess. The pair of flexible stretcher legs may be wrapped around a first foot of the sheet of material contacting the first side of the centerline and a relative foot of the sheet of material contacting the opposite side of the centerline. As the pair of stretcher legs are pushed further into the recess by an actuator that stretches the sheet of material relative to the centerline, the first foot and the opposing foot are pushed outwardly away from each other.

[0014] At least a proximal portion of the elongated shaft may extend along the longitudinal axis. The distal region of the elongated shaft may be angled with the longitudinal axis. The distal region of the elongated shaft may have a maximum outer diameter of no greater than about 1.3 mm. The distal-most end of the elongated shaft may be blunt to allow dissection between tissues of the eye without cutting the tissue. The tubular outer sheath may be a hypotube having an inner diameter of less than about 0.036" to about 0.009". The implant cut from the sheet of material may have a size that substantially fills the inner diameter of the tubular outer sheath.

[0015] The tubular outer sheath can be coupled to the first actuator and the inner elongated member is coupled to the second actuator. The first actuator can be located on the lower surface of the handle, which is configured to retract the tubular outer sheath proximally, and the second actuator can be located on the upper surface of the handle, which is configured to advance the inner elongated member distally. The distal advancement of the inner elongated member can push the implant distally through the lumen of the tubular outer sheath into a preparatory position near the distal opening of the lumen of the self-tubular outer sheath. The proximal retraction of the tubular outer sheath when the inner elongated member remains stationary relative to the handle can cause the implant to be disengaged from the elongated shaft to be deployed in the eye.

[0016] The tubular outer sheath may be a guide tube that is movable through the lumen of the fixed outer tube. The inner elongated member may be movable within the guide tube. The guide tube may be more flexible than the inner elongated member, and the inner elongated member may be more flexible than the fixed outer tube. The inner elongated member may take on the shape of the fixed outer tube when retracted proximally, and relax back to a curved shape when extended distally out of the outer tube. When both the guide tube and the inner elongated member are extended distally out of the outer tube, the guide tube may conform to the curved shape of the inner elongated member.

[0017] In an interrelated aspect, a box is provided for use with a system for preparing an implant and inserting the implant into an eye. The box includes a base having an upper surface defining a recess, the size and shape of the recess being designed to receive a sheet of material to be cut into an implant. The box includes a cover that is movably coupled to the base between an open configuration and a closed configuration. The cover has a lower surface that is arranged to be juxtaposed with the upper surface of the base when the cover is in the closed configuration. The box includes a cutting member that can be moved to a cutting configuration relative to the base and the recess. When the cutting member moves toward the cutting configuration, the cutting member cuts the sheet of material into an implant. Once the implant is cut, it is axially aligned with the lumen of the tubular outer sheath for delivery into the eye.

[0018] When the lid is in the closed configuration, the sheet of material may remain fixed relative to the base.When the lid is in the closed configuration, the sheet of material may be compressed within the recess.The lid may be configured to exert tension on the sheet of material compressed within the recess.

[0019] In an interrelated aspect, a method of preparing an implant for implantation in an eye of a patient and inserting the implant into the eye of the patient is provided. The method includes inserting a sheet of material into a proximal portion of an instrument. The instrument also includes a cutting member and a distal portion sized to be inserted into the eye. The method includes cutting the sheet with the cutting member to form the implant. The method includes advancing the implant from the proximal portion of the instrument to a deployment position in the lumen of an elongated tubular member of the distal portion. The method includes inserting the distal portion of the instrument into the anterior chamber of the eye. The method includes positioning the distal portion adjacent to ocular tissue and deploying the implant from the instrument.

[0020] Inserting the sheet of material may include inserting the sheet into a recess in the proximal portion and closing a cover over the recess. The cover may be adapted to engage at least a portion of the sheet of material prior to cutting. At least a portion of the cover may be transparent. The cover may prevent movement of the sheet during cutting of the sheet with the cutting member. The method may also include tensioning at least a portion of the sheet of material prior to cutting the sheet of material. The portion of the tensioning sheet may include a first portion and a second portion of the compression sheet and a central portion of the tensioning sheet, the central portion being located between the first portion and the second portion. The central portion of the sheet may include an implant when the sheet is cut with the cutting member. The portion of the tensioning sheet may include activating an actuator to tension the portion of the sheet. Activating the actuator may include rotating the actuator to tension the portion of the sheet. The cover may include an actuator, and actuation of the actuator tensions at least a portion of the sheet. The method may also include inserting a distal portion of the instrument into the anterior chamber through an intracorneal incision, while the proximal portion of the instrument remains outside the eye. The material may be a biologically derived material suitable for implantation into the eye. The bioderived material may be tissue harvested from a donor or from a patient, or may be an autograft, allograft, or xenograft material. The material may be an engineered material or a 3D printed material suitable for implantation. The implant may include one or more therapeutic agents.

[0021] Deployment of implants from the instrument may result in the implant being at least partially residing between the ciliary body and the sclera of the patient's eye. The implant may reside in the ciliary body detachment gap between the ciliary body and the sclera. The cutting member may include a cutting member lumen, a distal opening, and a pair of opposing cutting edges. Cutting may include advancing the cutting member to cut a sheet of material and capture the implant in the cutting member lumen. This pair of opposing cutting edges may cut the sheet at two locations to separate the implant from the rest of the sheet. The inner diameter of the elongated tubular member may be substantially the same as the inner diameter of the cutting member lumen. The distal portion of the cutting member may be beveled. The implant may include a longitudinal axis. When the cutting member completes the cutting sheet to form the implant, the longitudinal axis of the implant may remain aligned with the longitudinal axis of the lumen of the elongated tubular member.

[0022] Advancing the implant from the proximal portion of the instrument may include pushing the implant out of the lumen of the cutting member and into the lumen of the elongated tubular member of the distal portion. The distal region of the elongated tubular member may be at least one of angled or curved or flexible. The method may also include activating a first actuator to tension at least a portion of the blade before cutting; activating a second actuator to advance the cutting member to cut the blade after tensioning; activating a third actuator to advance the implant to a deployment position; and activating a fourth actuator to deploy the implant from the instrument, wherein each actuator is operatively coupled to the instrument.

[0023] Positioning the distal portion adjacent to the ocular tissue may include positioning the implant between the ciliary body and the sclera while the implant is at least partially retained within the lumen of the distal portion. Deploying the implant from the instrument may include retracting the elongated tubular portion from the implant while maintaining the position of the implant relative to the adjacent ocular tissue. The distal-most end of the elongated tubular member may be blunt to allow dissection of ocular tissue without cutting the ocular tissue. Closing the cover over the recess may include engaging a portion of the cover with a first portion of the sheet to compress the first portion of the sheet and tension the second portion of the sheet.

[0024] This disclosure also discloses the following items:

[0025] 1. A system for preparing an implant and inserting the implant into an eye, the system comprising:

[0026] a handle including one or more actuators;

[0027] an elongated shaft extending in a distal direction from the handle, the elongated shaft comprising a tubular outer sheath and an inner elongated member positioned within the lumen of the tubular outer sheath;

[0028] a recess sized to hold the sheet of material in place relative to the handle;

[0029] a cutting member movable relative to the handle and the recess into a cutting configuration,

[0030] wherein, when the cutting member moves toward the cutting configuration, the cutting member cuts the sheet of material into an implant, and wherein, once the implant is cut, it is axially aligned with the inner cavity of the tubular outer sheath, and further wherein the inner slender member is capable of moving relative to the tubular outer sheath to advance the implant to a deployment position in the inner cavity of the tubular outer sheath for delivery into the eye.

[0031] 2. A system according to item 1, wherein the sheet of material comprises a biologically derived material suitable for implantation into the eye.

[0032] 3. A system according to item 2, wherein the biologically derived material comprises tissue collected from a donor or from the eye.

[0033] 4. A system according to item 2, wherein the biologically derived material is an autologous graft, an allogeneic graft, or a xenograft material.

[0034] 5. The system of claim 1, wherein the material is engineered tissue.

[0035] 6. The system of claim 5, wherein the engineered tissue is a 3D printed material suitable for implantation.

[0036] 7. A system according to item 2, wherein the bio-derived material has a permeability and / or a strong structure to allow aqueous outflow from the eye when the implant cut from the material sheet is positioned within the ciliary detachment cleft.

[0037] 8. A system according to item 1, wherein the implant cut from the sheet of material is bioresorbable or non-bioresorbable.

[0038] 9. The system of claim 1, wherein the implant comprises one or more therapeutic agents.

[0039] 10. A system according to item 9, wherein the one or more therapeutic agents include anti-proliferative agents, anti-fibrotic agents, anesthetics, analgesics, cell transport / mobility inhibitors, anti-glaucoma drugs, prostaglandin analogs, carbonic anhydrase inhibitors, neuroprotectants, antibiotics, antivirals, anti-allergic agents, anti-inflammatory agents, mydriatics or immunomodulators.

[0040] 11. A system according to item 1, wherein the material sheet is compressed and / or tensioned before the cutting member moves to the cutting configuration.

[0041] 12. The system of claim 1, wherein the sheet of material is compressed between two juxtaposed planar surfaces to prevent movement during subsequent cutting of the sheet of material by the cutting member.

[0042] 13. A system according to item 1, wherein the material sheet is tensioned by a pair of flexible stretcher legs, and the flexible stretcher legs are configured to apply a stretching force away from the centerline of the material sheet.

[0043] 14. The system of item 1, further comprising a box removably coupled to a region of the handle, the box comprising a base and a cover, wherein the recess is located within the base of the box.

[0044] 15. The system of claim 1, wherein the recess is located within the handle.

[0045] 16. The system of item 11, further comprising an access door coupled to the handle and configured to enclose the recess when rotated to a closed configuration and to expose the recess when rotated to an open configuration.

[0046] 17. The system of item 16, wherein the access door is formed of a transparent or translucent material.

[0047] 18. The system of item 16 further comprises a protrusion extending upward from the centerline of the recess, thereby forming two channels within the recess on both sides of the protrusion, wherein the protrusion pushes the centerline of the material sheet upward toward the door.

[0048] 19. The system of item 18, wherein the sheet of material is captured between the protrusion and the access door when the access door is rotated relative to the handle to the closed configuration.

[0049] 20. The system of item 16, wherein the access door is configured to apply tension to the sheet of material when the access door is in the closed configuration.

[0050] 21. A system according to item 20, wherein the access door includes an actuator configured to apply tension, the actuator including a pair of flexible stretcher legs configured to extend into the recess, wherein the pair of flexible stretcher legs includes a first foot contacting the material sheet on a first side of the centerline and a relative foot contacting the material sheet on an opposite side of the centerline.

[0051] 22. A system according to item 21, wherein the first foot and the opposing foot are pushed outwardly away from each other when the pair of stretcher legs are pushed further into the recess by an actuator that stretches the material sheet relative to the centerline.

[0052] 23. A system according to item 1, wherein at least a proximal portion of the slender shaft extends along a longitudinal axis.

[0053] 24. A system according to item 23, wherein the distal region of the slender shaft is angled with respect to the longitudinal axis.

[0054] 25. A system according to item 1, wherein the distal end of the slender shaft is blunt to allow dissection between tissues of the eye without cutting the tissues.

[0055] 26. A system according to item 1, wherein the distal region of the slender shaft has a maximum outer diameter of no greater than about 1.3 mm.

[0056] 27. The system of item 1, wherein the tubular outer sheath is a hypotube having an inner diameter of less than about 0.036" to about 0.009".

[0057] 28. A system according to item 1, wherein the implant cut from the sheet of material has a size that substantially fills the inner diameter of the tubular outer sheath.

[0058] 29. The system of claim 1, wherein the tubular outer sheath is coupled to a first actuator and the inner elongated member is coupled to a second actuator.

[0059] 30. A system according to item 29, wherein the first actuator is located on the lower surface of the handle and is configured to retract the tubular outer sheath proximally, and the second actuator is located on the upper surface of the handle and is configured to advance the inner slender member distally.

[0060] 31. A system according to item 29, wherein distal advancement of the inner slender member pushes the implant distally through the inner cavity of the tubular outer sheath into a prepared position near the distal opening of the inner cavity of the tubular outer sheath.

[0061] 32. A system according to item 31, wherein proximal retraction of the tubular outer sheath while the inner slender member remains stationary relative to the handle causes the implant to be disengaged from the slender shaft to be deployed within the eye.

[0062] 33. The system of item 1, wherein the tubular outer sheath is a guide tube movable through the lumen of a fixed outer tube, and wherein the inner elongated member is movable within the guide tube.

[0063] 34. A system according to item 33, wherein the guide tube is more flexible than the inner slender member, and the inner slender member is more flexible than the fixed outer tube.

[0064] 35. A system according to item 33, wherein the inner slender member assumes the shape of the fixed outer tube when retracted proximally and relaxes back to a curved shape when extended distally out of the outer tube.

[0065] 36. A system according to item 35, wherein when the guide tube and the inner slender member are both extended distally out of the outer tube, the guide tube conforms to the curved shape of the inner slender member.

[0066] 37. A kit for use with a system for preparing an implant and inserting the implant intraocularly into an eye, the kit comprising:

[0067] a base having an upper surface defining a recess sized and shaped to receive a piece of material to be cut into an implant;

[0068] a cover movably connected to the base between an open configuration and a closed configuration, the cover having a lower surface arranged to be juxtaposed with the upper surface of the base when the cover is in the closed configuration; and

[0069] A cutting member capable of moving relative to the base and the recess into a cutting configuration, wherein the cutting member cuts the sheet of material into an implant as the cutting member moves toward the cutting configuration, and wherein the implant, once cut, is axially aligned with the inner cavity of the tubular outer sheath for delivery into the eye.

[0070] 38. A box according to item 37, wherein when the lid is in the closed configuration, the material sheet remains fixed relative to the base.

[0071] 39. A box according to item 37, wherein when the lid is in the closed configuration, the material sheet is compressed within the recess.

[0072] 40. The box according to item 37, wherein the cover is configured to exert tension on the material sheet compressed within the recess.

[0073] 41. A method of preparing an implant for implantation into an eye of a patient and inserting the implant into the eye of a patient, the method comprising:

[0074] inserting a sheet of material into a proximal portion of an instrument that also includes a cutting member and a distal portion sized for insertion into an eye;

[0075] cutting the sheet with a cutting member to form the implant;

[0076] advancing the implant from the proximal portion of the instrument to a deployment position within the lumen of the elongated tubular member of the distal portion;

[0077] inserting the distal portion of the instrument into the anterior chamber of the eye;

[0078] positioning the distal portion adjacent ocular tissue; and

[0079] The implant is deployed from the instrument.

[0080] 42. A method according to item 41, wherein inserting the sheet of material includes inserting the sheet into a recess in the proximal portion and closing a cover over the recess.

[0081] 43. A method according to item 42, wherein said cover is adapted to engage at least some portion of said sheet of material prior to said cutting.

[0082] 44. The method of item 42, wherein at least a portion of the cover is transparent.

[0083] 45. The method of clause 42, wherein the cover prevents movement of the sheet during cutting of the sheet by the cutting member.

[0084] 46. ​​The method of clause 41, further comprising tensioning at least a portion of the sheet of material prior to cutting the sheet of material.

[0085] 47. A method according to item 46, wherein tensioning the portion of the sheet includes compressing a first portion and a second portion of the sheet and tensioning a central portion of the sheet, the central portion being located between the first portion and the second portion.

[0086] 48. A method according to item 47, wherein the central portion of the sheet includes the implant when the sheet is cut with the cutting member.

[0087] 49. The method of claim 46, wherein tensioning the portion of the sheet comprises activating an actuator to tension the portion of the sheet.

[0088] 50. The method of clause 49, wherein activating the actuator comprises rotating the actuator to tension the portion of the sheet.

[0089] 51. The method of item 43, wherein the cover comprises an actuator, and wherein actuation of the actuator tensions at least a portion of the sheet.

[0090] 52. The method according to item 41 also includes inserting the distal portion of the instrument into the anterior chamber through the corneal incision, while the proximal portion of the instrument remains outside the eye.

[0091] 53. The method of claim 41, wherein the material comprises a biologically derived material suitable for implantation into an eye.

[0092] 54. A method according to item 53, wherein the biologically derived material comprises tissue collected from a donor or from a patient, or autologous graft, allograft or xenograft material.

[0093] 55. The method of claim 41, wherein the material comprises an engineered or 3D printed material suitable for implantation.

[0094] 56. The method of claim 41, wherein the implant comprises one or more therapeutic agents.

[0095] 57. A method according to item 41, wherein deployment of the implant from the instrument causes the implant to reside at least partially between the ciliary body and the sclera of the patient's eye.

[0096] 58. The method of item 57, wherein the implant resides between the ciliary body and the sclera within the ciliary detachment cleft.

[0097] 59. A method according to item 41, wherein the cutting member includes a cutting member lumen, a distal opening and a pair of opposing cutting edges, and wherein the cutting includes advancing the cutting member to cut the material sheet and capture the implant within the cutting member lumen.

[0098] 60. A method according to item 59, wherein the pair of opposing cutting edges cut the sheet at two locations to separate the implant from the rest of the sheet.

[0099] 61. The method of item 59, wherein the inner diameter of the elongated tubular member is substantially the same as the inner diameter of the inner lumen of the cutting member.

[0100] 62. A method according to item 59, wherein the distal portion of the cutting member is beveled.

[0101] 63. A method according to item 41, wherein the implant includes a longitudinal axis, and wherein, when the cutting member completes cutting the sheet to form the implant, the longitudinal axis of the implant remains aligned with the longitudinal axis of the inner cavity of the slender tubular member.

[0102] 64. A method according to item 59, wherein advancing the implant from the proximal portion of the instrument includes pushing the implant out of the inner cavity of the cutting member and into the inner cavity of the slender tubular member of the distal portion.

[0103] 65. A method according to item 41, wherein the distal region of the slender tubular member is at least one of angled or curved or flexible.

[0104] 66. The method according to item 41, wherein the method further comprises:

[0105] activating a first actuator to tension at least a portion of said sheet prior to said cutting;

[0106] activating a second actuator after said tensioning to advance said cutting member to cut said sheet;

[0107] activating a third actuator to advance the implant to the deployed position; and

[0108] A fourth actuator is activated to deploy the implant from the instrument, wherein each actuator is operatively coupled to the instrument.

[0109] 67. A method according to item 41, wherein positioning the distal portion adjacent to the ocular tissue includes positioning the implant between the ciliary body and the sclera, while the implant is at least partially retained within the inner cavity of the distal portion.

[0110] 68. A method according to item 41, wherein deploying the implant from the instrument includes retracting the elongated tubular portion from the implant while maintaining the position of the implant relative to adjacent ocular tissue.

[0111] 69. A method according to item 41, wherein the distal-most end of the slender tubular member is blunt to allow dissection of ocular tissue without cutting the ocular tissue.

[0112] 70. The method of clause 42, wherein closing the cover over the recess comprises engaging a portion of the cover with a first portion of the sheet to compress the first portion of the sheet and tension a second portion of the sheet.

[0113] The details of one or more variations of the subject matter described herein are set forth in the accompanying drawings and the description below. Other features and advantages of the subject matter described herein will become apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0114] These and other aspects will now be described in detail with reference to the following drawings. In general, these drawings are not absolute or relative to scale, but are intended to be illustrative. In addition, the relative placement of features and elements may be modified for clarity of illustration.

[0115] Figure 1 is a cross-sectional view of a human eye showing the anterior and posterior chambers of the eye with example locations of the stent in the eye;

[0116] Figure 2A and 2B An exemplary embodiment of a trephine device for forming a stent is shown;

[0117] Figure 3 shows a perspective view of an exemplary embodiment of a delivery device;

[0118] Figure 4 A cross-sectional view of the delivery device is shown;

[0119] Figure 5 An embodiment of a delivery device is shown with a trephine cartridge in an open configuration;

[0120] Fig. 6A An embodiment of a delivery device with a trephine cartridge in a closed configuration is shown;

[0121] Figure 6B yes Fig. 6Aa cross-sectional view of the device taken along line BB;

[0122] Figure 7 shows a partial view of a delivery device shaft having a sheet of biologically derived material extending through a cutout window;

[0123] Fig. 8A is a top view schematic diagram of a cutout window of a conveyor shaft;

[0124] Figure 8B yes Fig. 8A Sectional view along line BB;

[0125] Fig.9A is a perspective view of an embodiment of a trephine box;

[0126] Fig. 9B yes Fig.9A A cross-sectional view of a trephine box;

[0127] Fig. 9C yes Fig.9A A perspective view of the base of the trephine box;

[0128] Fig. 10A yes Fig.9A A perspective view of the trephine box relative to the cutting member;

[0129] Fig. 10B yes Fig. 10A a cross-sectional view of the trephine box with the cutting member partially inserted;

[0130] Fig. 10C yes Fig. 10A A cross-sectional view of the trephine box with the cutting member fully inserted;

[0131] Fig.11A yes Fig.9A a side view of a cutting member showing a blade relative to an axis of a delivery device loaded with a sheet of biologically derived material;

[0132] Fig. 11B yes Fig.11A a perspective view of a cutting member with the housing removed;

[0133] Fig. 11C is a side view of the blade relative to the conveyor shaft and the cutting support;

[0134] Fig.11D showing a side view of a cutting stent prepared within the lumen of a delivery device shaft;

[0135] Fig.11E is a distal end view of a delivery device shaft having a tubular outer sheath and an inner elongated member or pusher;

[0136] Figures 12A-12BThe distal region of the delivery device is shown;

[0137] Fig.13A is a top view of an embodiment of a delivery device;

[0138] Fig. 13B yes Fig.13A A bottom view of a conveying device;

[0139] Figures 14A-14B yes Fig.13A A partial view of a conveying device;

[0140] Figures 15A-15C is a schematic diagram of a stretcher for applying tension to a sheet of material;

[0141] Figures 16A-16B It is a schematic diagram of cutting a tube to cut a piece of material;

[0142] Figures 17A-17B is a schematic diagram of a pusher preparing a cutting bracket in a conveying shaft;

[0143] Fig.18A is a top view of an embodiment of a delivery device;

[0144] Fig.18B yes Fig.18A A bottom view of a conveying device;

[0145] Figures 19A-19B yes Fig.18A A partial view of a conveying device;

[0146] Figures 20A-20C A stretcher configured to apply tension to a sheet of material is shown;

[0147] Fig.21 yes Fig.18A A cross-sectional view of a delivery device showing a stretcher;

[0148] Fig. 22 Is to promote through Fig.18A A partial view of the device cutting the tube;

[0149] Figures 23A-23D yes Fig. 22 Detailed partial view of the cut pipe;

[0150] Figures 24A-24C is from Fig.18A A partial cross-sectional view of the cutting bracket released by the delivery shaft;

[0151] Fig.25 Is displayed for Fig.18A A partial cross-sectional view of the propulsion mechanism of the various axially movable parts of the device;

[0152] Fig.26is used for Fig.18A A partial cross-sectional view of the retraction mechanism of the guide tube of the device.

[0153] It should be understood that the drawings are merely schematic and are not intended to be drawn to scale. It should be understood that the devices described herein may include features that are not necessarily depicted in every drawing. DETAILED DESCRIPTION

[0154] Implants, systems and methods for increasing aqueous outflow from the anterior chamber of the eye are disclosed. As will be described in detail below, intraocular outflow stent implantation using biological, cell-based or tissue-based materials provides biocompatible aqueous outflow enhancement with improved tolerability and safety compared to conventional shunts. In an example embodiment, a trephine device or cutting tool is used to collect or generate biological tissue or biologically derived materials in vitro and form an implant, also referred to herein as a stent. In one embodiment, the stent is an elongated body or tissue strip that has no internal lumen. Lumen-based devices may be limited by the lumen as a fibrotic occluded channel. The stent formed by the tissue is then implanted into the eye via an intraocular delivery pathway to provide aqueous outflow from the anterior chamber. The stent described herein can be used as an adjunct to or stand-alone treatment for phacoemulsification of glaucoma as a minimally invasive glaucoma surgery (MIGS) treatment.

[0155] The use of terms such as stent, implant, shunt, biological tissue, or tissue is not intended to be limited to any one structure or material. The implanted structure may, but need not be, a material that is substantially absorbed into the ocular tissue after placement in the eye, such that once absorbed, space may remain where the structure was previously located. Once implanted, the structure may also remain in place for a long period of time and not substantially corrode or absorb.

[0156] As will be described in more detail below, the stents described herein can be made of biologically derived materials that do not cause toxic or harmful effects once implanted in a patient.

[0157] The term "biologically derived materials" includes naturally occurring biological materials and synthetic biological materials suitable for implantation into the eye and combinations thereof. Biologically derived materials include materials as natural biological structures having biological arrangements naturally occurring in mammalian subjects, including organs or organ parts formed by tissues, and tissues formed by materials grouped together according to structure and function. Biologically derived materials include tissues, such as cornea, sclera, or cartilage tissue. The tissues considered herein may include any of a variety of tissues, including muscle, epithelium, connective tissue, and neural tissue. Biologically derived materials include tissues, organs, organ parts, and tissues from subjects collected from donors or patients, including tissue blocks suitable for transplantation, including autologous transplants, allografts, and xenograft materials. Biologically derived materials include naturally occurring biological materials, including any materials naturally occurring in mammals. As used herein, biologically derived materials also include materials engineered to have biological arrangements similar to natural biological structures. For example, the material can be synthesized using in vitro techniques, such as by inoculating 3D scaffolds or matrix, engineering or 3D printing materials with appropriate cells to form a biological structure suitable for implantation. As used herein, biologically derived materials also include cell-derived materials, including stem cell-derived materials.

[0158] The biologically derived material used to form the scaffold, sometimes referred to herein as biological tissue or biomaterial, can vary and can be, for example, corneal tissue, scleral tissue, cartilage tissue, collagen tissue or other solid biological tissue. The biological tissue can be hydrophilic or hydrophobic. The biological tissue can include or be impregnated with one or more therapeutic agents for additional eye disease treatment procedures.

[0159] Non-biological materials include synthetic materials prepared by artificial synthesis, processing or manufacturing, which may be biocompatible but are not cell-based or tissue-based. For example, non-biological materials include polymers, copolymers, polymer blends and plastics. Non-biological materials include inorganic polymers such as silicone rubber, polysiloxanes, polysilanes and organic polymers such as polyethylene, polypropylene, polyethylene compounds, polyimides, etc.

[0160] Regardless of the source or type of the biologically derived material, the material can be cut or trepanned into an elongated shape suitable for stent implantation and implantation in the eye. Such trepanation of tissue can be performed prior to or during the surgical implantation process. The stent implanted in the eye can have a structure and / or permeability that allows aqueous humor to flow out of the anterior chamber when positioned within the ciliary body detachment cleft.

[0161] Figure 1is a cross-sectional view of a human eye showing the anterior chamber AC and the posterior chamber PC of the eye. Stent 105 can be positioned at an implantation location within the eye such that at least a first portion of stent 105 is positioned in the anterior chamber AC and a second portion of stent 105 is positioned within tissue, such as within the supraciliary space and / or the supraciliary space of the eye. Stent 105 is sized and shaped such that stent 105 can be positioned in such a configuration. Stent 105 provides or otherwise serves as a passage for aqueous humor to flow away from the anterior chamber AC (e.g., to the supraciliary space and / or the supraciliary space). Figure 1 In FIG. 1 , the support 105 is schematically shown as an elongated body. It should be understood that the size and shape of the support 105 may vary.

[0162] The support 105 can be implanted from the inner route, for example, through a clear corneal incision or scleral incision. The support can be implanted to create communication between the anterior chamber AC and the supraciliary space, the anterior chamber AC and the supraciliary space, the anterior chamber AC and the Schlemm's canal, or the anterior chamber AC and the subconjunctival space. In a preferred embodiment, the support 105 is implanted so that the distal end is positioned in the supraciliary position and the proximal end is positioned in the anterior chamber AC to provide a supraciliary fissure. The distal end of the support 105 can be positioned between other anatomical parts of the eye.

[0163] Conventional glaucoma stent implant devices are typically made of non-biological materials, such as polyimide or other synthetic materials, which can cause endothelial tissue damage, leading to progressive, long-term and irreversible corneal endothelial loss. The stent materials described herein can reduce and / or eliminate the risk of these tissue injuries while still providing enhanced aqueous humor outflow.

[0164] The support 105 described herein can be formed of any of a variety of biologically derived materials having a permeability and / or structure that allows water to filter therethrough. The support 105 can be formed of biologically derived materials that are collected, engineered, grown, or otherwise manufactured. The biologically derived support material can be obtained or collected from a patient or donor. The biologically derived support material can be collected before or during surgery. The biologically derived support material can be a synthetic biological tissue produced using in vitro techniques. The biologically derived material can be stem cell-generated or bioengineered. The tissue can be produced by in situ cell or non-cellular growth. In an example embodiment, the tissue can be 3D printed during manufacturing.

[0165] The 3D printed tissue can be printed as a larger sheet of material that is then cut during surgery, as described elsewhere herein. Alternatively, the 3D printed tissue can be printed to have the size of the final implantable stent. In this embodiment, the 3D printed material does not need to be trephinated before implantation, but can be implanted directly. For example, the 3D printed stent can be printed directly into a box that is configured to be operably coupled to a delivery device described herein, which in turn is used to deploy the 3D printed stent into the eye. The 3D printed stent can be generated using the 3D printing process described in Biofabrication, 2019; 11(3).

[0166] In an example embodiment, the support 105 is made of biological tissue. The biologically derived material can be corneal tissue and / or non-corneal tissue. The biologically derived material can include cornea, sclera, collagen or cartilage tissue. In one embodiment, the biologically derived support material can be a bare corneal stroma tissue without epithelium and endothelium, which is porous and has hydrophilic permeability to allow water filtration. The biologically derived material of the support 105 can but need not be incorporated into the inherent anatomical structure of the eye after being placed in the eye. The support can form a passage that remains open for a long time in the surrounding tissue, even after the support is absorbed. The biologically derived support material may not be significantly absorbed or incorporated into the anatomical structure of the eye, so that the support 105 remains implanted for a long time or indefinitely as needed.

[0167] In other embodiments, the scaffold 105 material can be made of complex carbohydrates or non-inflammatory collagen. The scaffold 105 can also be formed of biodegradable or bioabsorbable materials including biodegradable polymers, including hydroxy aliphatic carboxylic acids, which are homopolymers or copolymers, such as polylactic acid, polyglycolic acid, polylactic glycolic acid; polysaccharides, such as cellulose or cellulose derivatives such as ethyl cellulose, cross-linked or uncross-linked sodium carboxymethyl cellulose, sodium carboxymethyl cellulose starch, cellulose ethers, cellulose esters such as cellulose acetate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and calcium alginate, polypropylene, polybutyrate, polycarbonate, acrylate polymers such as polymethacrylate, polyanhydride, polyvalerate, polycaprolactone such as poly-c-caprolactone, polydimethylsiloxane, polyamide, polyvinyl pyrrolidone, polyvinyl alcohol phthalate, waxes such as paraffin and white beeswax, natural oils, shellac, zein or mixtures.

[0168] As mentioned above, biologically derived scaffold materials may have permeability or porosity that allows water to filter to fully control or regulate intraocular pressure. Permeable biological tissues described herein (such as sclera, cornea, collagen, etc.) are preferred scaffold materials, however, any biological tissue, even if impermeable, is also considered herein as a potential scaffold material for keeping the ciliary body from opening the structural spacer. Preferably, the material of the scaffold can produce a gap that allows fluid to flow. The gap produced can extend longitudinally along each side of the scaffold. If the material of the scaffold is permeable, then compared with the situation that the material of the scaffold is impermeable and the fluid needs to pass along the outside of the scaffold, more fluid can be detached from the ciliary body. Therefore, the material considered herein does not need to be porous to provide the desired function, however, the function can be enhanced by the porosity of the material.

[0169] Generally, biologically derived scaffold material has certain firmness, so that it can maintain the outflow from the anterior chamber, yet, its hardness is lower than the conventional non-biological derived polyimide shunt (for example Cypass, Alcon) for the treatment of glaucoma.Scaffold material can have enough structures to serve as spacers to support the outflow on the ciliary body that continues to be opened.Scaffold material can keep its structure height or thickness once implanted in the ciliary body detachment, so that the fluid flow by support or around support is provided.Compared with conventional non-biological materials (such as polyimide), biologically derived scaffold material provides advantages in biocompatibility, anatomical consistency and water permeability.Biologically derived scaffold material can provide better compliance and compliance to scleral wall, and over time and chronic eye friction and blinking cause the less possibility of endothelial and scleral erosion / loss.

[0170] In one embodiment, the material for forming the stent is provided as an uncut sheet of material that is configured to be manually loaded into a delivery device at the time of implantation. In other embodiments, the biologically derived material for forming the stent is provided as an uncut sheet that is preloaded in the shaft of the delivery device and held in a trepanation device 205 or box. In a further embodiment, the stent 105 has been cut into the shape of a stent that is preloaded in the delivery device shaft 310 or in a box that is configured to be loaded with the delivery device. The portion of the device that carries the biologically derived stent material (whether precut to the size of the stent or as a larger sheet size) can be packaged in such a way that the material is stored in a medium or other suitable preservative fluid for biologically derived materials. In some embodiments, the entire device is packaged in a liquid tank or a portion of the device is immersed in a separate container before the trepanation device or delivery device to which the entire device is attached at the surgical site.

[0171] After obtaining and preparing suitable materials, a trephine device can be used to produce an elongated stent of a predetermined size from a sheet of material. As will be discussed in more detail below, trephine can be performed during or before surgery. In some embodiments, the stent is formed by 3D printing and can be printed into the desired final size for the stent, or can be printed into a sheet of material, and then trephine is performed during or before surgery. The trephine achieved by the device described herein produces a very thin strip of material that can be implanted in the eye to provide regulation of water outflow. The trephine achieved positions the cut implant in the catheter or lumen of the delivery device so that the cut implant can be subsequently delivered from the delivery device without removing or transferring the cut implant from the cutting element to the delivery tube. The trephine process can load the cut implant into the delivery conduit simultaneously or in subsequent actuation to implant in the eye.

[0172] As used herein, the term "sheet of material" refers to a bioderived sheet of material that is larger in size along at least one dimension than a stent cut from the sheet of material and implanted into a subject. In some embodiments, the sheet of material may have a generally square shape and the stent trepanned from the sheet of material may have a generally rectangular shape. For example, the sheet of material may be approximately 7 mm wide x 7 mm long x 0.55 mm thick, and the stent trepanned from the sheet of material may be 0.3-0.6 mm wide x 7 mm long x 0.55 mm thick. The size of the sheet of material and the trepanned stent may vary. The sheet of material and the trepanned stent may each have the same length and the same thickness, but different widths from each other. The sheet of material and the stent trepanned from the sheet of material may also have different lengths and thicknesses. For example, the sheet of material may have a first thickness and the stent trepanned from the sheet of material may have the same thickness, but may be folded or rolled into a thickness different from the sheet of material when implanted.

[0173] The support trepanned from the sheet of material can have width, length and thickness. In one embodiment, the width of the support trepanned from the sheet of material using the trepanning device as 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. The support trepanned from the sheet of material can have a width of at least about 100 microns and a width of no more than 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, no more than 800 microns, no more than 700 microns, no more than 600 microns, no more than 500 microns, no more than 400 microns, no more than 300 microns or no more than 200 microns. The length of the support trepanned from the sheet of material can vary according to the position of the support implantation. In some embodiments, the length of the support is between 1mm and 10mm, or more preferably the length is between 3mm and 8mm. The thickness of the support trepanned from the sheet of material can be 100 microns to about 800 microns, or 150 microns to about 600 microns. In one embodiment, the biomaterial forming the support can have a thickness of not less than 100 microns and not more than 5mm. The thickness of the support can also depend on whether the support is folded or coiled when implanted, so that a sheet of material with a thickness of only 250 microns can be cut into the support and the support is folded when implanted to double the thickness to about 500 microns. The thickness of the support can also depend on what biologically derived material is used. For example, scleral tissue or corneal tissue can generally have a thickness of about 400 microns, but can shrink to about 250-300 microns after collection. Therefore, the support cut from the contracted corneal tissue sheet can only have a thickness of 250 microns. In some embodiments described in more detail below, the support cut from the sheet of material is cut to basically fill the conduit, which is advanced through the conduit for transportation.

[0174] In a non-limiting example, the biological tissue scaffold has a size of no less than 0.1 mm and no more than 8 mm in any direction and a thickness of no less than 50 microns and no more than 8 mm. In a non-limiting example, the scaffold is about 6 mm long, about 300-600 microns wide, and about 150-600 microns thick. The trephine may be no less than 1 mm and no more than 8 mm in any direction. In a non-limiting example, the trephine tissue has a size of 100-800 microns in width and a size of 1mm-10mm in length. It should be understood that multiple scaffolds can be delivered to one or more target locations during the implantation process.

[0175] The trephine device described herein provides accurate and precise cutting without wrinkling. The trephine device can be combined with front and rear capture so that the material to be cut remains fixed in the z-plane, preventing movement before the tissue engages with the cutter. In the embodiments described in more detail below, the material to be cut remains fixed, compressed and / or tensioned before cutting.

[0176] Figure 2A and 2B An exemplary embodiment of a trephine device 205 is shown. An intraoperative trephine device for forming a stent may be combined with or removably coupled to a delivery device, such as an applicator / injector for delivery to an implantation site. Figure 3-4 , Figures 13A-13B and Figures 18A-18B An embodiment of a trephine device integrated with a conveying device is shown. Figure 5 and 6A As shown in FIG. 6B , the trephine device may be a cartridge removably coupled to the delivery device. Figure 5 and Figure 6A-6B As shown, a box containing a sheet of material can be coupled to a distal portion of a delivery device. In this embodiment, the box can be removed from the delivery device before the stent is deployed into the eye. The box containing the sheet of material can alternatively be coupled to a proximal portion of the delivery device. In this embodiment, the box does not need to be removed before the stent is delivered into the eye, and the stent cut from the sheet of material can be deployed from the box coupled to the delivery device without a separate step.

[0177] The trephine device is configured to cut or otherwise form a biologically derived tissue or material sheet having a first profile or shape (e.g., a wider square sheet or material sheet) into a second profile or shape (e.g., a narrower rectangular material strip) that conforms to an implantable stent of the size described herein. The cutting performed using the trephine device described herein can involve a guillotine, stamping, rotating, sliding, rolling or pivoting blade cutting movement. In some embodiments, the cutting is performed perpendicular to the plane of the material sheet. In some embodiments, the cutting is performed axially along the implanted catheter. Therefore, the axis of the trephine can be aligned with the implant catheter, within the implant catheter or parallel to the implant catheter to allow unimpeded tissue loading and transfer for implantation without having to manipulate, tear or damage the fragile stent tissue. The trephine process can be preceded by a tissue fixation step, in which the biologically derived tissue forming the stent is firmly fixed between two juxtaposed planar surfaces to ensure that the tissue is not wrinkled or deformed, and the subsequent trephine cutting has an accurate size. Fixation can optionally provide tension or stretching of the tissue in at least one plane to ensure clean cutting through the tissue.

[0178] The trephine can be performed along or in the path or conduit formed in the structure, such as in a box, a conveying device or in any other structure. The trephine of the material sheet can simultaneously or subsequently position the implant in a conduit (e.g., the lumen of the conveying shaft) or align with the conduit, so that the implant cut can be delivered to the eye by the conduit, and the implant cut does not need to be transferred to a separate conveying device. In some embodiments, the cutting movement can be carried out from above the material sheet so that the sharp edge of the blade cuts the material sheet from the upper surface of the sheet. When the cutter slides over the material sheet forming the implant, it can then push the implant cut into the lumen of the conveying shaft along the axis orthogonal to the longitudinal axis A of the handle. In other embodiments, the cutting movement can slide through the material sheet from the proximal end of the handle 305 toward the distal end along the longitudinal axis A of the handle. The movement of the cutting can cause the implant cut to be correctly positioned and / or aligned with the conveying conduit of the conveying shaft. The cutting member can be movable relative to the handle and relative to the recess holding the material sheet in the cutting configuration. As the cutting member moves toward the cutting configuration, it can cut the sheet of material held fixed within the recess to form the implant, and the implant, once cut, can be delivered in axial alignment with the duct.

[0179] The method of preparing an implant for implanting an implant and inserting the implant into a patient's eye may include inserting a sheet of material into a proximal portion of an instrument. The instrument may include a cutting member and a distal portion of the eye that is sized to be inserted. The implant may be formed by cutting the sheet with the cutting member. When the cutting member completes cutting the sheet of material to form the implant, the implant, which may have a longitudinal axis, may be aligned with the longitudinal axis of the inner cavity of the cutting member that cuts the implant.

[0180] The implant can then be advanced from the proximal portion of the instrument to the deployment position in the inner cavity of the elongated tubular member of the distal portion of the instrument. The distal portion of the instrument can be inserted into the anterior chamber of the eye, so that it can be positioned adjacent to the eye tissue, and in the anterior chamber, the implant is deployed from the instrument into the eye tissue. For example, the distal portion of the instrument can be inserted into the anterior chamber through the corneal incision, and the proximal portion of the instrument is retained outside the eye. It should be understood that the distal portion of the instrument can be used for other delivery paths (e.g., delivered through the sclera). Implant deployment into the eye tissue can include that the implant resides at least partially between the ciliary body and the sclera of the eye. The implant can reside in the ciliary body detachment gap between the ciliary body and the sclera.

[0181] Inserting the sheet of material includes inserting the sheet into a recess, such as in a proximal portion of the instrument. The instrument may include a cover that closes over the recess containing the sheet. The cover is adapted to engage at least some portion of the sheet of material before cutting of the sheet of material occurs. The cover may prevent movement of the sheet during cutting of the sheet with the cutting member of the instrument. The cover (or some other element) may additionally apply tension to at least a portion of the sheet before cutting occurs. The tensioning may involve activating an actuator to tension that portion of the sheet, although the tensioning need not involve a separate actuation and may be the result of closing the cover itself. Closing the cover over the recess may include engaging a portion of the cover with a first portion of the sheet to compress the first portion of the sheet and tension a second portion of the sheet.

[0182] Preferably, the structure trepans the tissue in such a manner that the tissue can be slid, pushed and / or pulled along the catheter toward the implantation site in the eye. In other embodiments, the stent is held fixed in place and the catheter is withdrawn from the stent, leaving the stent implanted in the eye. The catheter can be incorporated into or coupled to a delivery device that implants and deploys the stent into the eye. The trepanation device can be made of any of a variety of materials, such as hard materials including plastic and / or metal.

[0183] Figure 2A-2B The trephine device 205 shown in FIG. 20 can have an internal lumen or housing 210 that is sized and shaped to form the elongated profile of the stent 105 when the tissue is positioned within the housing 210. The housing 210 has dimensions that approximate, within microns, the size of the stent 105 to be formed. The trephine device 205 is configured to stabilize the tissue during the trephination process. In this regard, the trephine device 205 can secure the tissue in place and prevent the tissue from moving relative to the trephine device 205 while being trephinated. In one embodiment, the trephine device 205 can have one or more wings 215 that are configured to, when opened ( Figure 2A ) and close( Figure 2B ) configuration. When the trephine device 205 is in the open configuration, a sheet of material can be placed within the housing 210. One or more blades 220 can be positioned on the inner surface of the wings 215 so that when the wings 215 are hinged to the closed configuration and the sheet of material is in place within the housing 210, the sheet is cut into a stent having a desired size.

[0184] The housing 210 of the trephine device 205 can be transformed into and / or contain a corresponding lumen of a delivery device 110 configured to advance or otherwise inject the stent 105 into the eye. In one embodiment, the trephine device 205 trephine or cuts tissue along a path aligned or coaxial with the delivery path of the stent into the implantation position. For example, a stent cut from a sheet of material retained in the housing 210 can be pushed distally through the lumen extending through the front end 222 of the trephine device 205 into the delivery device shaft. Therefore, the stent can be trephinated using an independent trephine device first. The trephine device holding the trephine stent can then be loaded into a delivery device that is designed to receive the trephine device. This allows the stent to be loaded and deployed without removing the stent from the trephine device to load it into the delivery device.

[0185] Trephination of stent material will be described in more detail below.

[0186] Reference again Figure 1 The delivery device 110 is configured to be removably coupled to the stent 105 and used to deliver the stent 105 to the implantation site through the intra-path delivery path. Figure 1 When coupled, the delivery device 110 can be inserted into the eye and used to implant the stent 105 to the implantation site via an intraocular delivery pathway.

[0187] The delivery devices described herein can prepare the implant and perform intraocular insertion of the implant into the eye. Figure 3 A perspective view of an example embodiment of a delivery device 110 with an integrated trephine is shown. Figure 4 Shows Figure 3 10. The delivery device 110 may include a proximal handle 305 that is sized and shaped to be grasped by a single hand of a user. One or more actuators 315 may be positioned on the area of ​​the handle 305. The actuator 315 may also be manipulated by a single hand of the user, such as with a thumb or finger. The actuator 315 may be one or more of a knob, button, slider, or other interface that is configured to move one or more components of the delivery device 110, as will be described in more detail below.

[0188] The elongated shaft 310 (also referred to herein as an applicator or delivery body) extends outwardly from the handle 305 in a distal direction. At least a portion of the shaft 310 contains or is coupled to the stent 105 for direct stent implantation. At least a portion of the shaft 310 extends along the longitudinal axis A. The shaft 310 can be angled, curved or flexible in the distal region so that it can form a distal bend or flexure. In some embodiments, the shaft 310 can include a flexible portion and a rigid portion so that the shape of the shaft changes depending on the relative position of these portions. The shaft 310 can be curved and / or can be flexible at least along its length.

[0189] The size and shape of the shaft 310 of the delivery device 110 are configured for intraocular delivery through a clear corneal incision to allow the stent 105 to pass from the distal end of the shaft 310 and remain in the eye. In at least some methods, the distal end of the shaft 310 is sized to extend through an incision of about 1 mm in length. In another embodiment, the distal end of the shaft 310 is sized to extend through an incision of no more than about 2.5 mm in length. In another embodiment, the distal end of the shaft 310 is sized to extend through an incision between 1.5 mm and 2.85 mm in length. In some embodiments, the maximum outer diameter of the shaft 310 is no greater than 1.3 mm. The distal end 316 of the shaft 310 can be blunt or sharp. The blunt distal end 316 of the shaft 310 allows dissection between ocular tissues without penetrating or cutting tissue to position the stent 105. For example, the distal end 316 of the shaft 310 can be configured to be blunt between the ciliary body CB and the sclera S (e.g., the supraciliary space), while the stent 105 remains completely enclosed within the shaft 310 during blunt dissection. In an alternative embodiment, the distal end 316 of the shaft 310 has a sharp cutting configuration for dissection and implantation through the scleral wall into the subconjunctival space. In yet another embodiment, the distal end 316 can have a cutting configuration for dissection and implantation in Schlemm's canal or transscleral dissection and implantation.

[0190] The stent described herein is formed as a solid material strip without any lumen. Therefore, the stent cannot be delivered by a guide wire like many conventional glaucoma shunts. In addition, the stent is formed by relatively soft tissue, which is more fragile because the general shunt is formed by a more rigid polymer or metal material. A more rigid shunt can be implanted so that the distal end of the shunt is used to produce blunt dissection at the tissue interface through which the shunt is inserted. The stent described herein is preferably deployed using a retractable cannula type syringe, which can be retracted once in the appropriate anatomical position, so that the stent is more gently externalized and positioned. In addition, the stent described herein can be deployed in the eye by pushing the stent distally through at least a portion of the shaft 310. The stent may have a size that substantially fills the internal lumen of the shaft 310 (or the internal lumen of at least a portion of the shaft 310 through which the stent is delivered) so that the stent can be pushed distally through the portion without wrinkling or being damaged. The tolerance between the external dimensions of the stent 105 and the internal dimensions of the catheter can be up to about 200%. The catheter may also be coated with a lubricious material (eg, Teflon) to improve advancement of the stent 105 through the catheter during deployment.

[0191] The shaft 310 can define an internal hollow shape for receiving the stent 105. In some embodiments, the shaft 310 can be formed by an outer tube 318 (also referred to herein as a tubular outer sheath) and an inner pusher 320 (also referred to herein as an elongated member) positioned within the lumen of the outer tube 318 (see Figure 4 , see also Figure 7 , 11C -11E). Movement of the outer tube 318 and / or the pusher 320 can serve to deploy the stent 105 in the eye. The outer tube 318 and the pusher 320 of the shaft 310 are operatively coupled to one or more actuators 315 to deliver the stent 105 to the eye. The outer tube 318 can be fixed relative to the handle 305 and the pusher 320 can be moved relative to the handle 305. The outer tube 318 can be moved relative to the handle 305 and the pusher 320 can be fixed relative to the handle 305. Alternatively, both the outer tube 318 and the pusher 320 can be moved relative to the handle 305. The movement of the outer tube 318 and / or the pusher 320 can be generated using the same actuator 315 on the handle 305 or a different actuator 315, which can be actuated by the user moving the actuator 315 relative to the handle 305. The type of movement of the actuator 315 relative to the handle 305 can be different, including sliding or rotational movement. Figure 3 and Figure 4 The embodiment shown in FIG. 304 may include a shaft 310 having an outer tube 318 and a pusher 320. The outer tube 318 may be coupled to a slider and the pusher 320 may be coupled to a knob 311 located at a proximal region of the handle 305.

[0192] Once the distal end of shaft 310 reaches the desired location in the tissue, stent 105 is left in place in the eye and shaft 310 is withdrawn. In one embodiment, outer tube 318 of shaft 310 is retracted, for example using actuator 315 on the handle, while pusher 320 remains stationary relative to handle 305. Pusher 320 can thus act as a stopper, preventing stent 105 from following outer tube 318 as it is retracted. The result is that stent 105 is withdrawn from shaft 310 and remains within the tissue.

[0193] The delivery device 110 may also include a cutting member 312 (see Figure 4 ), such as a blade or cutting tube, which can be moved relative to the handle 305 to cut tissue to form the stent 105. As described above, the stent 105 can be formed from a sheet of material. The sheet of material can be loaded in the area of ​​the delivery device 110 and cut into smaller stent shapes during delivery. The cutting member 312 can be actuated by the user to produce a stent from the sheet of material.

[0194] In an exemplary embodiment, the cutting member 312 is attached to a cover 314 that is movable relative to the handle 305 (see Figure 3-4 ). The cover 314 can be coupled to the distal region of the handle 305 via a hinge 317 so that the cover 314 can rotate relative to the handle 305 about the pivot axis P of the hinge 317. The cover 314 can be lifted to pivot into an open configuration (see Figure 3 ), exposing a recess 321 in which the sheet of material 101 can be positioned and held stationary relative to the handle. When the cover 314 is rotated about the pivot axis P back to the closed configuration, the sheet of material 101 located within the recess 321 is compressed and / or tensioned between the cover 314 and the handle 305. The compression and / or tensioning of the sheet of material 101 can help ensure a clean and complete cut of the material. In some embodiments, the sheet of material 101 can be placed under tension, such as by stretching the cover 314 outwardly, prior to cutting with the cutting member 312. The sheet of material 101 can be stretched outward from the cutting position, such as Figures 15A-15C shown.

[0195] The recess 321 may be in the proximal portion of the instrument, for example with a portion of the handle 305. The recess 321 for holding the sheet of material 101 may also be a recess in a box removably coupled to a portion of the instrument, for example in the area of ​​the handle 305 or coupled to the distal portion of the instrument.

[0196] It should be understood that tensioning the sheet may include activating a separate actuator to tension the sheet. Tensioning may also be achieved during the stabilization and compression steps without separate actuation. For example, simply closing the lid 314 may result in compression and tensioning of the sheet of material without the need for a separate actuator to provide tension on the sheet of material after compression.

[0197] The cover 314 can be opened in any of a number of orientations relative to the handle. For example, the pivot axis P of the hinge 317 can be substantially orthogonal to the longitudinal axis A of the handle. In this embodiment, the hinge 317 can be positioned at the distal end of the handle 305, between the shaft and the cover 314, so that the cover 314 is hinged open by rotating upward and toward the shaft (see, e.g., Figure 3 and Figure 4 Alternatively, hinge 317 may be positioned so that cover 314 hinges open by rotating upward and toward the proximal region of handle 305 (see, e.g. Figure 5 and 6A -6B). In still other embodiments, the hinge 317 can be positioned on one side of the handle 305 so that the pivot axis P and the longitudinal axis A are substantially parallel to each other. In this embodiment, the cover 314 can swing outward away from the longitudinal axis A of the handle 305 (see, e.g. Figures 15A-15C ). Any of a variety of configurations are considered in this paper.

[0198] The cutting member 312 may extend from a lower surface of the cover 314 to cut the sheet of material 101 (eg, biological tissue) in a guillotine-like manner. Figure 4 The cover 314 is shown in an open configuration, which is raised from the recess 321, and the material sheet 101 is located in the recess 321. The cutting member 312 can extend from the lower surface of the cover 314 so that its cutting surface penetrates the material sheet 101. In some embodiments, the cutting member 312 is coupled to a movable actuator or button 313, which can be actuated to move the cutting member 312 from the in-sheath configuration to the cutting configuration. Once the cover 314 is in a closed configuration to compress and / or stretch the material sheet 101 between the lower surface of the cover 314 and the housing 305, the movable actuator 313 can be pushed downward relative to the cover 314, thereby placing the cutting member 312 in the cutting configuration. The cutting member 312 can extend below the lower surface of the cover 314 and cut through the material sheet 101 held in the recess 321. One of the plurality of return springs 323 can push the actuator 313 back upward so that the cutting member 312 is in the in-sheath configuration again. As the cutting member moves toward the cutting configuration, the cutting member 312 cuts the sheet of material into the implant. The implant, once cut, is also axially aligned with the lumen of the shaft.

[0199] It should be understood that other types of cutting mechanisms may be used. For example, lowering the cover 314 may also cut the material sheet 101 held in the recess 321 in a rotational cutting movement. In this embodiment, the cutting member 312 extends below the plane of the lower surface of the cover 314 so that the blade can be used to cut the material sheet 101 when the cover 314 is rotated to the closed configuration. Alternatively, the cutting movement may be an axial cutting movement using a slidable cutting tube so that trephination occurs along the implant catheter, which is different from a cutting movement perpendicular to the plane of the material sheet 101.

[0200] As described above, as the cutting member moves toward the cutting configuration, it cuts the material sheet into implants. Once the implant is cut, it is also aligned axially with the inner cavity of the shaft to be deployed in the eye. Therefore, the movement of the cutting member 312 simultaneously cuts the stent and places the cut stent to a position relative to the shaft 310 so that the stent can be delivered by the shaft 310. The cutting member 312 can include a pair of blades separated by a spacer in order to cut the material sheet 101 into a rectangular stent shape. The spacer between the pair of blades can engage with the cut stent 105 after the blade cutting to push the stent 105 downward through the narrow slot in the outer tube 318. The pusher 320 can be in a fully retracted configuration by the knob 311, so that the inner cavity of the outer tube 318 is free to receive the cut stent 105 through the narrow slot. It should be understood that the stent 105 can be pushed downward to a position relative to the delivery device that aligns the stent 105 with the implantation path instead of being specifically loaded into the inner cavity of the outer tube 318. For example, loading into the lumen of the outer tube 318 can occur after additional steps such as advancing the stent 105 toward the lumen of the outer tube 318 after cutting. A variety of sheath loading configurations are contemplated herein, including top loading, front loading, rear loading, and side loading as described above, which will be described in more detail below. Regardless of the configuration, the trephination of the sheet of material 101 can place the stent 105 in a position that allows it to be deployed into the eye (i.e., axially aligned with the lumen of the shaft) without the need for manual tissue transfer of the tiny cut sheet of material.

[0201] Figure 5 Another embodiment of the delivery device 110 is shown. This embodiment has a removable trephine box 205 near the end of the delivery device 110. This embodiment reduces or minimizes the distance the stent 105 travels once the stent has been formed within the lumen of the shaft 310.

[0202] and Figure 3 and 4As with the previous embodiments shown, the delivery device 110 may include a proximal handle 305 having one or more actuators 315 and a shaft 310 extending from a distal region of the handle 305. The actuator 315 may include first and second sliders configured to respectively move an outer sheath and a pusher of the shaft 310. It should be understood that the device 110 need not incorporate multiple actuators 315 to achieve movement of multiple components. For example, the device 110 may include a single actuator 315 configured to cut and deploy the stent 105, such as by causing movement of both the outer sheath and the pusher based on, for example, the degree of actuation of the sliders.

[0203] The trephination box 205 may include a base 324 and a cover 314 movably attached to the base 324. The cover 314 and the base 324 may be coupled together by a hinge 317 so that the cover 314 rotates about the pivot of the hinge 317. As with the previous embodiment, the cover 314 may be lifted to pivot to an open configuration, thereby exposing a recess 321 of the base 324 within which a sheet of material may be positioned and held stationary. When the cover 314 is rotated back to the closed configuration, the sheet is compressed and / or tensioned between the cover 314 and the base 324. The cover 314 and the base 324 do not need to be hinged relative to each other. For example, the cover 314 and the base 324 may simply disengage, exposing the upper surface of the base 324 so that the shaft 310 and the sheet of material 101 may be properly positioned relative to the trephination box 205. Cover 314 may be configured to additionally exert an amount of tension on piece of material 101, such as stretching in an outward direction from the center of piece of material 101 to improve cutting.

[0204] Fig. 6A The delivery device 110 is shown having the trephine box 205 coupled to the distal region of the handle 305 in a closed configuration in which an upper surface of the base 324 and a lower surface of the cover 314 of the trephine box 205 abut against each other. Figure 6B yes Fig. 6A 10, showing a shaft 310 extending through the handle 305.

[0205] The trephine box 205 can be provided in a manner preloaded with a sheet of material positioned in the recess. For example, the sheet of material can be compressed and / or tensioned in the base 324 and the cover 314. The cutting member 312 can then be actuated to punch out the stent 105 from the sheet of material, for example, by pushing the cutting member 312 through the sheet of material held in the trephine box 205 by pressing the button 313. The delivery device 110 and the trephine box 205 can then engage with each other. For example, the shaft 310 can be inserted through the proximal port on the trephine box 205, thereby front loading the cut stent 105 into the outer tube 318 for delivery to the eye. The cut stent 105 can remain fixed in the trephine box 205. In further embodiments, the stent can be loaded from above the shaft, or front loaded or loaded from the rear of the shaft into the incision opening in the shaft.

[0206] It should be understood that when implanting a subject, it is not necessary for the user to cut the sheet of material into a stent. The sheet of material can be cut into a stent long before the implantation time, for example, in a tissue bank or tissue engineering laboratory. The stent can be provided as a pre-cut, pre-loaded stent in a box configured to be coupled to a conveying device. For example, a trephine box 205 can be provided to the user, which is pre-loaded with a pre-cut stent 105 from a biologically derived sheet of material. The box 205 holding the stent 105 can be coupled to the conveying device when implanted. Once coupled together, the user can load the stent 105 into the shaft 310 of the conveying device, as described elsewhere herein. In a further embodiment, the stent 105 can be provided to the user, which is pre-loaded in the lumen of the shaft 310. The sheet of material can be provided in the box or in the lumen of the shaft 310, and it is known in the art to be immersed in a suitable tissue antiseptic medium.

[0207] In one embodiment, a user may manually load the sheet of material 101 through opposing cutout windows 326 extending through the outer tube 318 of the shaft 310 of the delivery device 110 (see Figure 7 ). The cutout windows 326 in the outer tube 318 can extend through the opposing side walls so that the sheet of material 101 can be inserted through a first cutout window 326, across the lumen 328 of the outer tube 318, and inserted through a second cutout window 326 on the opposite side of the lumen 328. The size of the cutout 326 is sufficient to load the sheet of material 101 through the cutout 326, such as Figure 7 The sheet of material 101 can have a dimension that is wider than the outer diameter of the outer tube 318, such that each side of the sheet 101 extends beyond the sidewalls of the outer tube 318. The cutout windows 326 in the outer tube 318 can each have a length along the longitudinal axis A of the shaft 310 that is at least as long as the length of the sheet of material 101. The cutout windows 326 in the outer tube 318 can have a depth that is at least as thick as the thickness of the sheet of material 101. Fig. 8A 3 is a schematic top view of the cutout window 326 of the shaft 310 . Figure 8B It is taken along line BB Fig. 8A The cutout windows 326 , which may be created by removing the sidewalls on either side of the outer tube 318 , form narrow webs 330 on the upper and lower surfaces of the tube 318 .

[0208] Figures 9A-9B Another embodiment of a trephine box 205 having a cover 314 and a base 324 is shown. Fig.9A A base 324 is shown with the top cover 314 mounted thereto. Fig. 9B is a cross-sectional view of the box 205 showing the tissue piece 101 sandwiched between the base 324 and the cover 314. Fig. 9C The base 324 of the trephine box 205 is shown loaded with a sheet of material 101. The window 326 of the tube 318 is positioned outside and within the recess 321 of the base 324. The recess 321 can be positioned between the proximal slot 332 and the distal slot 334. The proximal slot 332 is sized to receive at least a portion of the outer tube 318 proximal to the incision window 326 and the distal slot 334 is sized to receive a portion of the outer tube 318 distal to the incision window 326. The recess 321 can have any of a variety of shapes, but can be generally sized to receive the sheet of material 101 loaded within the incision window 326 of the outer tube 318. Thus, when the shaft 310 of the delivery device 110 is inserted into the trephine box 205, the shaft 310 is received within the proximal and distal slots 332, 334 and the tissue sheet 101 is positioned within the recess 321.

[0209] Still about Figures 9A-9C , the cover 314 can have an upper surface that forms the outer surface of the box 205. The cover 314 can also include a lower surface configured to engage with the upper surface of the box base 324. The upper surface can include a recess 336, within which is the entrance of a hole 338, which extends from the upper surface through the entire thickness of the cover 314 to the lower surface. The upper surface of the box base 324 includes an entrance of a hole 340, which extends through at least a certain thickness of the base 324. The hole 340 of the base 324 can, but does not have to, extend through the entire thickness of the base 324. When the cover 314 abuts the base 324, the holes 338, 340 are aligned, thereby forming a continuous channel. The size and shape of the continuous channel are designed to receive the cutting member 312, which will be described in more detail below. The cutting member 312 can translate relative to the box 205 and extend from the upper surface of the cover 314 through the entire thickness of the cover 314 into the hole 340 of the base 324.

[0210] The lower surface of the cover 314 surrounding the hole 338 in the cover 314 and the upper surface of the base 324 surrounding the hole 340 in the base 324 can compress the material sheet 101 located therebetween. The recess 321 in the base 324 can have a depth that is less than the thickness of the sheet 101 positioned within the recess 321, so that when the cover 314 is coupled to the base 324, the material sheet 101 is compressed between the cover 314 and the base 324. The compression of the material sheet 101 between the base 324 and the cover 314 helps prevent the material sheet 101 from moving with the cutting member 312 during cutting. Tension can also be applied to the material 101 sheet between cuts. In some embodiments, the cover 314 is hinged relative to the base 324 (see Figure 5 ). The cover 314 and the base 324 can be reversibly secured to each other so that when the cover 314 is closed onto the base 324, the cover 314 latches or is otherwise reversibly coupled to the base 324 to prevent the cover 314 from being accidentally opened relative to the base 324.

[0211] Fig. 10A The trephine box 205 is shown with the base 324 and the cover 314 in a closed configuration. Fig. 10B is a cross-sectional view of the trephine box 205 in a closed configuration, with the sheet of material 101 sandwiched between the cover 314 and the base 324 , and the cutting member 312 inserted into the aperture 338 of the cover 314 . Fig. 10C is a cross-sectional view of the trephine box 205 with the cutting member 312 fully advanced through the cover 314 and into the aperture 340 of the base 324 .

[0212] The cutting member 312 may include a pair of blades 344 and an enlarged gripping feature or handle 343. The handle 343 is located at the upper end of the blade housing 342, while the pair of blades 344 protrude from the lower end of the blade housing 342. The shape and size of the handle 343 can be designed to allow the user to comfortably grip the cutting member 312. Figures 10A-10C The handle 343 is shown having a disc shape configured to be received within a correspondingly shaped recess 336 in the upper surface of the cover 314. Any of a variety of shapes are contemplated herein.

[0213] The blade housing 342 may include a central channel 346 within which an upper portion of the blade 344 is received. The lower cutting surface of the blade 344 extends below the blade housing 342. The pair of blades 344 may be separated from each other by a spacer 345 defining a gap between the blades 344. The size of the gap is selected based on the desired width of the support 105 to be achieved when the tissue piece 101 is cut with the blades 344.

[0214] The cutting member 312 can be received in the recess 336 in the cover 314 so that the blade 344 extending from the lower end of the cutting member 312 is first inserted through the hole 338 in the cover 314, followed by the blade housing 342 (see Fig. 10A ). Thus, the size and shape of the hole 338 of the cover 314 can be designed to receive not only the blade 344, but also at least a portion of the blade housing 342. The handle 343 can be sized and shaped to be received in the recess 336 in the cover when the cutting member 312 is fully inserted into the cartridge 205.

[0215] The tissue piece held within the incision area of ​​the shaft is cut at two locations, creating a narrow strip of material (i.e., stent 105) from the sheet of material 101. As the cutting member 312 is pushed further through the hole 338 in the cover 314, the blade 344 is pushed toward the sheet of material 101 compressed between the cover 314 and the base 324 (see Fig. 10B As the cutter is pushed further through the hole 338 of the cover 314 and into the hole 340 of the base 324, the blade 344 cuts through the tissue piece 101 located in the recess 321 (see Fig. 10C ). When the blade 344 extends downward through the hole 340 of the base 324 to completely cut through the sheet 101, the blade 344 makes two cuts in the sheet of material 101 to form the stent 105. As the cutting member moves toward the cutting configuration, the movement of the cutter toward the cutting configuration cuts the sheet of material into the stent, and the stent, once cut, is axially aligned with the lumen 328 of the outer tube 318. The formed stent 105 is thus already loaded relative to or within the lumen 328 of the outer tube 318, so no loading step is required.

[0216] The blade 344 has been inserted through the continuous passage formed by the holes 338, 340 of the cover 314 and the base 324. The housing 342 can be seated in the hole 338 and / or the handle 343 can be seated in the recess 336 of the cover 314 to prevent any further downward movement of the blade 344. The support 105 is formed to be snugly retained within the lumen 328 of the outer tube 318. As described above, the outer tube 318 of the delivery device shaft 310 can include a pair of cutout windows 326 on opposite side walls, and narrow webs 330 are formed on the upper and lower surfaces of the tube 318. As shown in FIG. Figures 11A-11E326, when the cutting member 312 is inserted into the cartridge 205, each blade 344 is received within a corresponding cutout window 326 of the tube 318 such that the blade 344 extends into the hole 340 in the base 324. The gap between the pair of blades 344 is sized to accommodate and receive the web 330 as the blades 344 slide over the shaft 318 positioned within the cartridge 205. Once cut, the stent 105 is contained within the lumen 328 of the outer tube 318 at the location of the cutout window 326, with one of the pair of blades 344 surrounding the stent 105 on a first side and the second of the pair of blades 344 surrounding the stent 105 on a second side. The outer shell forms a path for the stent 105 to be deployed out of the lumen 328 to the distal end of the shaft 310, as will be described in more detail below.

[0217] Still about Figures 11A-11E , the blade 344 may include a single beveled edge that is angled to deliver an incision, similar to scissors. Preferably, the blade 344 does not cut tissue. The blade 344 is positioned relative to the box 205 so that a complete cut through the sheet 101 occurs when the cutting member 312 is fully advanced through the box 205.

[0218] When the cutting member 312 is fully translated into the cover 314 (i.e., the cutting member 312 is placed in the cutting configuration), the blade housing 342 is constrained within the hole 338 in the cover 314. Thus, the length of the blade housing 342 is no longer than, and preferably slightly shorter than, the depth of the hole 338 in the cover 314. Fig. 10B As best shown, the distal exit of the aperture 338 at the lower surface of the cover 314 can have a smaller size than the entrance of the aperture 338. Where the entrance of the aperture 338 is sized to receive the blade housing 342, the exit of the aperture 338 can be sized to receive only the blade 344 and not the blade housing 342. This arrangement can prevent over-insertion of the cutting member 312 relative to the cartridge 205 because the lower end region of the aperture 338 acts as a stopper for the blade housing 342.

[0219] The cutting member 312 may also include a safety sheath (not shown) configured to surround the dual blades 344 extending from the lower end of the blade housing 342. The safety sheath may prevent accidental damage to the blades 344 or the user when the cutting member 312 is not engaged with the box 205. For example, the safety sheath may enclose the blades 344 in all portions other than the lower end of the cutting member 312. The cover 314 and base 324 of the box 205 may include additional channels that are aligned, sized, and shaped to receive the safety sheath around the blades 344 when the cutting member 312 is inserted into the box 205.

[0220] Fig.11EA cross-sectional view of the cutout window 326 of the outer tube 318 is shown, wherein the blades 344 are located on either side of the upper web 330 and the lower web 330. As described above, the shaft 310 of the delivery device 110 can include a pusher 320 that is located within the lumen 328 of the outer tube 318. At least a portion of the pusher 320 can have a cross-sectional shape that is configured to slide over the blades 344 located within the cutout window 326 of the tube 318. The cross-sectional shape of at least a portion of the pusher 320 can include a flat side that is configured to align with the cutout window 326 when the pusher 320 is extended relative to the outer tube 318 during deployment of the stent 105 from the lumen 328. The flat side (as opposed to the convex side) of the pusher 320 can define a width that is sized to slide between the two blades 344 located within the cutout window 326. As with the stent, at least a portion of the pusher 320 can be sized to completely fill at least a portion of the lumen 328 of the outer tube 318. The outer tube 318 can be a hypotube that is no larger than about 18G (0.050" OD, 0.033" ID), 20G (0.036" OD, 0.023" ID), 21G (0.032" OD, 0.020" ID), 22G (0.028" OD, 0.016" ID), 23G (0.025" OD, 0.013" ID), 25G (0.020" OD, 0.010" ID), 27G (0.016" OD, 0.008" ID), 30G (0.012" OD, 0.006" ID), or 32G (0.009" OD, 0.004" ID). In some embodiments, outer tube 318 is a hypotube having an inner diameter of less than about 0.036" to about 0.009". The size of outer tube 318 can be selected based on the desired size of the stent to be implanted, as discussed in more detail above.

[0221] When the shaft 310 of the delivery device 110 is installed in the cartridge 205 and the blade 344 is still positioned in the cutting configuration, the pusher 320 can be pushed distally away from the handle 305 of the delivery device 110 to position the stent 105 cut from the sheet of material 101 into a prepared position within the lumen 328. In some embodiments, the pusher 320 can be advanced distally relative to the handle 305, for example, using an actuator 315 on the handle 305. The presence of the blades 344 on either side of the cut window 326 and the webs 330 on the upper and lower sides prevents the stent 105 from buckling within the lumen 328 during this preparation step. The size of the catheter in which the stent 105 is retained matches the outer dimensions of the stent being implanted, thereby preventing buckling and wrinkling when the stent 105 is pushed into the prepared position.

[0222] Once the stent 105 is pushed into the distal end region of the outer tube 318, the blade 344 can be retracted from the base 324. In some embodiments, the cutting member 312 can be removed from the cartridge 205 and the cover 314 can be opened relative to the base 324 so that the shaft 310 of the delivery device 110 can be removed from the cartridge 205. In other embodiments, the cutting member 312 can be withdrawn from the base 324 but still engaged with the cartridge 205 to remove the shaft 310 of the delivery device 110 from the cartridge 205. The shaft 310 can be withdrawn from the cartridge 205 regardless of whether the cover 314 is in the open configuration or not. Once the delivery device 110 and the cartridge 205 are disengaged from each other, the delivery device 110 is ready for insertion of the stent 105 into the eye, which will be described in more detail below.

[0223] As described above, movement of components of the delivery device 110 may be accomplished using one or more actuators 315 of the handle 305 . Figure 6B is a cross-sectional view of an embodiment of a delivery device 110 with a distal shaft 310 engaged with a trephine cartridge 205. The shaft 310 can include a pusher 320 and an outer tube 318. The pusher 320 can be coupled to a first actuator 315 and the outer tube 318 can be coupled to a second actuator 315. Each of the first and second actuators 315 can be a slide configured to advance and retract their respective components. The first actuator 315 can be withdrawn proximally so that the pusher 320 is in its most proximal position relative to the outer tube 318 during cutting of the sheet of material 101 compressed and / or tensioned within the cartridge 205. Once the sheet of material 101 is cut, the user can advance the first actuator 315 to push the pusher 320 distally, thereby preparing the stent 105 within the lumen 328 of the outer tube 318 toward the distal end of the shaft 310. After the cutting stent 105 is prepared to its distal position within the lumen 328, the cartridge 205 can be detached from the shaft 310. The outer tube 318 of the delivery device 110 can be used to dissect tissue of the eye until the target location is approached. Once the delivery device is in position to deploy the stent 105 in the eye, the first actuator 315 coupled to the pusher 320 can be maintained in the distal position and the second actuator 315 can be withdrawn to retract the outer tube 318. This relative movement of the outer tube 318 to the pusher 320 deploys the stent 105 from the lumen 328 into the anatomical structure (e.g., Fig. 12B 328). It should be appreciated that additional distal movement of the pusher 320 can be used to assist in the deployment of the stent 105 from the lumen 328. It should also be appreciated that the pusher 320 advancement and outer tube 318 retraction can be controlled by dual actuators 315, as described above, or by a single actuator 315 that can move the pusher and outer sheath depending on the degree of actuation. In addition, the shaft 310 of the delivery device 110 can be used to inject a viscoelastic substance during surgery using the pusher 320 as a plunger.

[0224] Figures 13A-13B and Figures 18A-18B A related embodiment of a delivery device 1110 is shown, which has an integrated trephine drill to form a system for preparing an implant and performing an intraocular insertion of the implant into an eye. As described elsewhere herein, the delivery device 1110 can be inserted into the eye and used to implant the stent 105 at the implantation site via an intraocular delivery pathway. The delivery device 1110 may include a proximal portion, such as a proximal handle 1305, which is sized and shaped to be grasped by a user and remain outside the patient's eye. The delivery device 1110 may also include a distal portion. The distal portion may include an elongated delivery shaft 1310 extending distally from the proximal handle 1305. The elongated delivery shaft 1310 includes an outer tube 1318 having an inner lumen 1328 (see Fig.14A ). An axially movable cutting tube 1312 can be positioned within the handle 1305. A pusher 1320 is shown positioned within the lumen 1378 of the cutting tube 1312. The pusher 1320 is configured to be advanced distally through the lumen 1328 of the outer tube 1318. It should be understood that where the delivery device is described herein as being suitable for performing an intra-insertion of an implant, other methods of implantation are also contemplated. For example, the delivery device can be used to perform a trans-scleral approach for delivering an implant.

[0225] Still about Fig.14A , the delivery device 1110 can include an access door 1314 coupled to a region of the handle 1305, such as by a hinge 1317, such that the door 1314 can rotate relative to the handle 1305 about a pivot of the hinge 1317. When the access door 1314 is in an open configuration, the recess 1321 is exposed. The sheet of material 101 can be loaded into the recess 1321 for cutting into the stent 105 prior to delivery. The pusher 1320 positioned within the lumen 1378 of the cutting tube 1312 is retracted proximally relative to the recess 1321 so that the sheet of material 101 can be positioned within the recess 1321. Fig. 14B The access door 1314 is shown rotated to a closed configuration, thereby capturing the material piece 101 within the recess 1321. In some embodiments, the access door 1314 can be formed of a transparent or translucent material so that the material piece 101 positioned within the recess 1321 can be viewed by the user after loading (see also Fig.18A ). The access door 1314 may also include one or more latches 1322 (see Fig.19A ) to ensure that once the door 1314 is closed it remains closed until the user wishes to again open the door 1314. In some embodiments, the latch of the access door 1314 may include an interference fit feature or a magnet, or other element.

[0226] The recess may be in a portion of the instrument, such as in a handle as described above. The recess may also be in a box that is removably coupled to the instrument. As shown herein, the box may be coupled to the distal portion of the instrument and removed prior to deployment into the eye. The box may also be coupled to the proximal portion of the instrument and may or may not be removed prior to deployment.

[0227] When the door 1314 is rotated about the pivot axis P from the open configuration to the closed configuration, the material sheet 101 located in the recess 1321 can be captured, compressed and / or tensioned. The door 1314 can be adapted to engage at least some portion of the material sheet before the sheet is cut. The door 1314 can prevent the sheet from moving during cutting with the cutter.

[0228] In some embodiments, at least a portion of recess 1321 can have a depth less than the thickness of sheet 101 held within recess 1321, for example, the portion is aligned with the centerline of the implant catheter. When door 1314 is closed, sheet 101 is slightly compressed.

[0229] At least a portion of the sheet of material 101 can be placed under tension prior to cutting. When the sheet of material 101 is placed under slight tension prior to cutting, the cutting effected by the cutting tube 1312 is improved. Tensioning the portion of the sheet can include compressing a first portion and a second portion of the sheet and tensioning a central portion of the sheet, the central portion being located between the first and second portions. When the sheet is cut with the cutting tube 1312, the central portion of the sheet becomes the implant.

[0230] Tensioning the portion of the sheet can include activating an actuator to tension the portion of the sheet. Activating the actuator can include rotating the actuator to tension the portion of the sheet. For example, the cover can include an actuator and actuation of the actuator can tension at least a portion of the sheet. However, tensioning need not be a separate actuation. As discussed elsewhere herein, closing the access door 1314 can provide fixation and a certain amount of tension to the sheet. Figures 15A-15C 1 is a cross-sectional schematic diagram of the handle 1305 showing the access door 1314 and the material sheet 101 positioned within the recess 1321. The door 1314 may include features configured to apply a small amount of tension or stretching force on the material sheet 101 to improve cutting. The door 1314 may be coupled to a stretcher 1350 having a pair of flexible stretcher legs 1352. The stretcher legs 1352 extend into the recess 1312 until each foot 1354 at the end of the leg 1352 contacts the material sheet 101 (see FIG. 1 ). Fig. 15B). One foot 1354 can contact a first portion of the sheet of material 101 on a first side of the centerline, and an opposing foot 1354 can contact a second portion of the sheet of material 101 on an opposing second side of the centerline. The stretcher 1350 can be actuated from a first position in which the stretcher 1350 is elevated relative to the recess 1321. When the stretcher 1350 is pushed downward, the stretcher legs bend and the feet 1354 are pushed outward further away from the centerline and away from each other (see Fig. 15C ). The distance between the feet 1354 is sufficient to allow the cutting tube to slide through the recess 1321 between the feet 1354 in the axial direction to cut the material sheet 101. The lower surface of the feet 1354 can have surface features 1355, such as ridges, bumps or other textures that optimize the interface between the feet 1354 and the material sheet 101. The surface features 1355 allow the feet 1354 to stretch the material sheet 101 outward when the feet 1355 are pushed outward.

[0231] The stretcher 1350 can have any of a variety of configurations. The stretcher 1350 can be Figures 13A-13B and buttons shown in 15A-15C. The stretcher 1350 may be as shown in Figures 18A-18B , Figures 19A-19B , Figures 20A-20C , Fig.21 and Fig. 22 Any of a variety of other actuators 101 that are configured to apply tension to the sheet are contemplated. In embodiments where the tensioner 1350 is a button, the door 1314 may additionally incorporate a tension release button 1357 (see FIG. Fig.13A ) to release the applied tension.

[0232] Regardless of the configuration, the tensioner 1350 can have an upper end region 1360 and a lower end region 1362 (see Fig. 20A ). Upper end region 1360 is configured to be grasped and actuated (ie, pushed or rotated). Lower end region 1362 of stretcher 1350 can engage with access door 1314. Fig.21 An embodiment of a tensioner 1350 is shown that is a dial having threads 1367 on a lower end region 1362 of the tensioner 1350 that engage corresponding threads 1365 of a hole 1364 in an upper surface of the door 1314. Rotation of the tensioner 1350 relative to the hole 1364 pulls the tensioner 1350 further downward into the hole 1364 and pushes the foot 1354 further into the recess 1312.

[0233] As discussed elsewhere herein, tensioning the sheet can include activating an actuator, such as a dial, to tension the sheet. Tensioning can also be achieved without a separate actuation. For example, closing the door 1314 can achieve both securing and tensioning of the sheet of material without requiring a separate actuator to provide tension on the sheet of material after compression. Thus, the door 1314 can achieve a preset tension on the sheet of material when closed without requiring a separate activation of the stretcher 1350 upward or downward relative to the material.

[0234] The recess 1321 receives the sheet of material 101. The recess 1321 may include an inverted V-shaped protrusion 1371 that may protrude upward from the centerline of the recess 1321, which pushes the centerline of the sheet of material 101 upward toward the door 1314 while allowing the sides of the sheet of material 101 to hang downward into corresponding channels 1370 on either side of the centerline (see Fig.19A and Fig.21 ). When the door 1314 is closed, the stretcher legs 1352 extend into the recess 1312 until each foot 1354 of the stretcher legs 1352 contacts the side of the sheet of material 101 suspended within the channel 1370 (see Fig.21 ). One foot 1354 can contact a first portion of the sheet of material 101 in a first channel 1370 adjacent to the centerline, and an opposing foot 1354 can contact a second portion of the sheet of material 101 in a second channel 1370 on the opposite side of the centerline. As the stretcher 1350 is pulled further into the hole 1364, such as by turning a dial, the feet 1354 push the portions deeper into their respective channels 1370, thereby pressing the centerline of the sheet of material 101 against the inverted V-shape 1371 of the recess 1321 (see Fig.21 ). The distance between the feet 1354 is sufficient to allow the cutting tube 1312 to pass therebetween. The inverted V-shape 1371 may include a shallow central channel 1372 sized and shaped to receive the lower wall geometry of the cutting tube 1312 as it is advanced distally to cut the sheet of material 101.

[0235] The cutting member may include a cutting member lumen, a distal opening and a pair of relative cutting edges. Cutting may include advancing the cutting member to cut the sheet of material and capture the implant in the cutting member lumen. The pair of relative cutting edges may cut the sheet at two positions to separate the implant from the rest of the sheet of material. The distal portion of the cutting member may be an inclined surface. When the cutting member completes the cutting of the sheet to form the implant, the longitudinal axis of the implant may remain aligned with the longitudinal axis of the lumen of the cutting member.

[0236] The cutting tube 1312 may be a double-bevel hypotube forming two guide points 1372 (see Figures 23A-23D). When the cutting tube 1312 is advanced to the cutting configuration and cuts through the block of material 101, the two guide points 1372 can be located above and below the block of material 101, respectively. The lower guide point 1372 can be received within the shallow center channel 1372 of the inverted V-shape 1371 and the upper guide point 1372 slides on the piece of material 101. The guide points 1372 can be blunt or sharp. The cutting surface of the cutting tube 1312 includes an inner edge 1374 of each bevel 1376. The inner edges 1374 are separated from each other by the inner cavity 1378 of the cutting tube 1312, so that the cutting tube 1312 cuts the piece of material 101 at two locations. Therefore, the inner diameter or distance between the inner edges 1374 of the cutting tube 1312 determines the width of the stent 105 that is cut.

[0237] Once cut, the stent 105 is contained within the lumen 1378 of the cutting tube 1312, thereby forming a shell for the stent 105. The stent 105 can be sized to substantially fill the lumen 1378 of the cutting tube 1312. Axial movement of the cutting tube 1312 in a distal direction toward the cutting configuration positions the cutting tube 1312 such that its walls bridge the recess 1321 and form a portion of the implant catheter 1319. The lumen 1378 of the cutting tube 1312 can be coaxial (e.g., connected or not connected) with the lumen of the elongated shaft 1310 through which the stent 105 will be delivered to the eye. For example, as Fig. 17B As shown, the cut stent 105 can be pushed out of the cutting tube 1312 along the implant catheter 1319 toward the distal end of the delivery shaft 1310. Therefore, the axial movement of the cutting tube 1312 along the axis of the implant catheter 1319 simultaneously cuts the stent from the material sheet 101 and aligns the cut stent with or relative to the delivery shaft lumen axially, so that the stent 105 can be deployed in the eye without any tissue transfer step.

[0238] The inner elongated member or pusher 1320 is movable relative to the lumen of the delivery shaft. The stent 105 can be pushed distally from the cutting tube 1312 by the pusher 1320. As described above, the elongated shaft 1310 of the delivery device 1110 can include an outer tube 1318 and an inner pusher 1320 located within the lumen of the outer tube 1318. The pusher 1320 is sized and shaped to travel distally through the lumen 1378 of the cutting tube 1312 to push the stent 105 toward the distal end of the outer tube 1318 (see FIG. 1 ). Fig. 17B ). In some embodiments, outer tube 1318 is fixed relative to handle 1305 and inner pusher 1320 is movable relative to outer tube 1318 to deploy stent 105 from outer tube 1318. In other embodiments, outer tube 1318 and pusher 1320 are movable relative to handle 1305 and relative to each other. The distal end of pusher 1320 can be shaped to atraumatically push stent 105 in a distal direction.

[0239] In further embodiments, the elongated delivery shaft 1310 may include a fixed outer tube 1318 and a guide tube 1380 positioned and movable through the lumen 1328 of the outer tube 1318 (see Figures 18A-18B ). The pusher 1320 can in turn be movable through the lumen 1382 of the guide tube 1380. The distal region of the elongated tubular member for delivering an implant into an eye can be angled, curved and / or flexible. In some embodiments, the guide tube 1380 can have a curved shape in its distal region and / or the guide tube 1380 can be flexible to conform to the curved shape. The curved shape of the distal region of the guide tube 1380 can conform to the shape of the desired implant location, such as the curvature of the eye near the anterior angle. The outer tube 1318 can be a rigid tube and the guide tube 1380 can be flexible. The pusher 1320 can be a shaped nitinol that takes on the shape of the rigid outer tube 1318 when retracted proximally and is allowed to relax back to its shaped configuration (i.e., having a bend or flexure away from the longitudinal axis of the outer tube 1318) when extended distally beyond the distal opening of the outer tube 1318. When the pusher 1320 extends beyond the outer tube 1318, the guide tube 1380 can be flexible enough to take on the shape of the pusher 1320. Thus, the guide tube 1380 can be more flexible than the pusher 1320 and the pusher 1320 can be more flexible than the outer tube 1318. In some embodiments, the guide tube 1380 can be formed of silicone, a thermoplastic elastomer, polyethylene, polypropylene, or a combination thereof. The guide tube 1380 can have a certain degree of hardness, but not so hard that it cannot be retracted by the pusher 1320 during deployment.

[0240] After the stent 105 is cut by the cutting tube 1312, the guide tube 1380 and the pusher 1320 can work together to deploy the stent 105 in the eye. The pusher 1320 can push the stent 105 out of the lumen 1378 of the cutting tube 1312 and into the lumen 1382 of the guide tube 1380. Fig.24A The guide tube 1380 is shown extending through the lumen 1378 of the cutting tube 1312 and extending beyond the distal end of the outer tube 1318. The stent 105 is located within the lumen 1382 of the guide tube 1380 which is pushed distally by the pusher 1320, which is also located within the lumen 1382 of the guide tube 1380. The stent 105 is pushed distally through the lumen 1382 by the pusher 1320 until the stent 105 is located within the distal region of the guide tube 1380 ( Fig. 24B). In this deployment stage, pusher 1320 has been advanced a distance beyond the distal end of rigid outer tube 1318 so that pusher 1320 can relax back to its bent or flexed shape. Guide tube 1380, which can be more flexible than pusher 1320, assumes the shape of pusher 1320. The cut stent 105 in this prepared position near the distal end of guide tube 1380 is ready to be implanted in the eye. Guide tube 1380 can be retracted while pusher 1320 remains stationary to effectively push stent 105 out of the lumen of guide tube 1380 (see Fig.24C ).

[0241] Advancing the implant from the proximal portion of the instrument may include pushing the implant out of the cutting member lumen and into the lumen of the elongated tubular member of the distal portion. The distal portion of the instrument may be positioned near ocular tissue to position the implant in the eye, such as between the ciliary body and the sclera, while the implant is at least partially retained in the lumen of the distal portion of the instrument. The support 105 may be deployed from the instrument when the guide tube 1380 is retracted from the implant while maintaining the position of the implant relative to adjacent ocular tissue. The implantation and delivery methods of the support 105 are described in more detail below.

[0242] Movement of the cutting and deployment components (e.g., one or more of the cutting tube 1312, the pusher 1320, the guide tube 1380, and the outer tube 1318, if present) can be accomplished by one or more actuators 1315 located on one or more regions of the handle 1305. In some embodiments, one or more actuators 1315 for a first function of the delivery device 1110 can be located on a first region of the handle 1305, and one or more actuators 1315 for a second function of the delivery device 1110 can be located on a second region of the handle 1305. A first plurality of actuators 1315 can be located on a first region of the handle 1305 to prepare a sheet of material 101 into a stent, and a second plurality of actuators 1315 can be located on a second region of the handle 1305 to deploy a stent 105 cut from the sheet 101. For example, the top region of the handle 1305 may include a first actuator 1315 for capturing and / or stretching the sheet of material 101, a second actuator 1315 for moving the cutting tube 1312 to cut the sheet of material 101, and a third actuator 1315 for moving the pusher 1320 to position the cut stent 105 to a ready position for deployment from the device 1110. The bottom region of the handle 1305 may include a fourth actuator 1315 for deploying the stent 105 in the eye.

[0243] Fig.13A shows a top view of an embodiment of a delivery device 1110, Fig. 13BA bottom view of the device 1110 is shown. The top region of the handle 1305 may include a first actuator 1315, which is a stretcher 1350 for capturing and stretching the material sheet 101 within the recess; and another actuator 1315, which is a slider for moving the cutting tube 1312. The bottom region of the handle 1305 may include an actuator 1315, which is a slider for moving a pusher 1320 to push the bracket 105 from the outer tube 1318.

[0244] Fig.18A shows a top view of an embodiment of a delivery device 1110, Fig.18B A bottom view of the device 1110 is shown. The top region of the handle 1305 may include a first actuator 1315, which is a stretcher 1350 for capturing and stretching the material sheet 101 within the recess, a second actuator 1315, which is a slider for moving the cutting tube 1312, and a third actuator 1315, which is a wheel for incrementally advancing the pusher 1320. The bottom region of the handle 1305 may include a fourth actuator 1315, which is a spring retract button for retracting the guide tube 1380 to release the bracket 105 from the shaft 1310.

[0245] The configuration of the actuator 1315 can vary. For example, the actuator 1315 can include any of a variety of sliders, dials, buttons, knobs, or other types of actuators.

[0246] In one embodiment, the one or more actuators 1315 configured to axially move one or more components of the device may include rollers 1385 (see Fig.25 ). The roller 1385 can be connected to a pinion 1387, which engages with a corresponding rack 1389. The rotation of the pinion 1387 can cause the rack 1389 to move axially and advance or retract any axially movable component, such as the pusher 1320 or the cutting tube 1312. Fig.25 A rack 1389 is shown attached to the pusher 1320. The roller 1385 can provide more incremental, precise movement of components. A roller advancement mechanism is described in US 10,154,924 and is incorporated herein by reference.

[0247] In another embodiment, the one or more actuators 1315 configured to axially move one or more components of the device may include a spring-loaded button 1390. The guide tube 1380 may be pushed in a distal direction in an extended state relative to the handle 1305, which compresses the front spring 1392 (see Fig.26). The button 1390 can be held in a forward locked position by a latch 1394 so that the spring 1392 remains compressed during advancement of the stent 105 to the target position in the eye. When a downward force is applied to the button 1390, the latch 1394 is released, allowing the spring 1392 to push the guide tube 1380 proximally a distance, thereby retracting the guide tube 1380. The retraction of the guide tube 1380 relative to the pusher 1320 can be used to release the implant 105 in the eye. A spring-loaded retraction mechanism is described in US9,241,832 and is incorporated herein by reference.

[0248] Activating the first actuator can tension at least a portion of the sheet before cutting, activating the second actuator can advance the cutting member to cut the sheet after tensioning, activating the third actuator can advance the implant to the deployment position, and activating the fourth actuator can deploy the implant from the instrument. Each actuator is operably coupled to the instrument. It should also be understood that one or more steps in cutting the implant and / or deploying the implant from the instrument can be combined. For example, the first actuator can fix, compress and tension the portion of the sheet before cutting, the second actuator can advance the cutting member and advance the cut implant to the deployment position, and then the third actuator deploys the implant from the instrument into the eye. Advancing the implant from the proximal portion of the instrument can include pushing the implant out of the cutting member lumen and into the lumen of the elongated tubular member of the distal portion.

[0249] The advancement of the cutting tube 1312 can cut the stent 105 from the sheet of material, resulting in the stent 105 being positioned within the lumen of the cutting tube 1312. The inner diameter of the cutting tube 1312 can be substantially the same as the inner diameter of the outer guide tube 1380. The pusher 1320 can be pushed distally through the lumen of the cutting tube 1312, pushing the cut stent 105 within the lumen into the lumen of the guide tube 1380. However, because the inner dimensions of the cutting tube 1312 and the guide tube 1380 can be substantially the same, when the guide tube 1380 is pushed proximally by the spring, the cutting tube 1312 can be pushed backward by the guide tube 1380. The stent 105 can be substantially contained within the implant catheter and is advanced line-to-line within the device as it is pushed distally. Once the stent 105 is cut from the sheet of material, the implantation path of the stent 105 can include the lumen of the cutting tube 1312, the lumen of the guide tube 1380, and any other conduits therebetween, so that the entire delivery process of the stent within the implantation catheter avoids the transfer between the "gaps" or "edges" that are necessary in the implantation catheter. The implantation catheter provides a smooth path for deploying the stent 105 through the instrument.

[0250] The trephination of tissue and the loading of tissue using a delivery device can be performed simultaneously or sequentially. In a preferred embodiment, the cutting and injection are integrated. This allows the cutting / trephination of tissue to be performed in / along the implantation path. The size of the tissue strip is such that manipulating it may be difficult. Therefore, by integrating the cutting and implantation, no additional manipulation is required. The tissue can be cut and loaded into the tissue delivery path without removing or manipulating the tissue outside the cutting device before transfer to the intraocular applicator. The same device can be used to trephine the tissue to form a scaffold, which is then injected / implanted into the eye, thereby achieving seamless and non-traumatic loading of fine, micro-sized bioscaffold tissue without the need for transport manipulation.

[0251] The tissue may be, for example, cornea, sclera, or other cartilaginous tissue. A section of tissue is cut using a delivery device and / or a cutting device. The tissue is loaded into a tissue delivery path that at least partially includes the eye without completely removing the tissue from the cutting device prior to transfer to the intraocular delivery device. In the case of using a single integrated trephine / injection device, the device is used for trephination of tissue and injection and implantation of tissue into the eye.

[0252] In another embodiment, simultaneous or sequential tissue trephination and insertion of tissue into the eye is performed. Tissue segments are cut and loaded into a tissue delivery path. This is performed using a single device that is configured to trephine tissue and is configured to load the trephinated tissue into an intraocular delivery applicator to administer the tissue to the eye.

[0253] The application device can also be used as a delivery device and a loading platform device or conduit. In such an implant, the device is configured to contain or otherwise accommodate tissue prior to implantation. The device allows longitudinal or other directional movement of the tissue for implantation into the eye. The device can be configured to trephine and apply loading to the tissue simultaneously or sequentially, so that after the trephine step is completed, the trephine or cut tissue is loaded into the delivery conduit of the application device. The trephine device can be coupled to the intraocular delivery device by a coupling or other attachment mechanism, which helps transfer the tissue into the delivery device.

[0254] The stent can be harvested from the patient during surgery by a trephine device. The stent can also be formed from a sheet of material obtained from a donor or other tissue engineering source. The sheet of material can be pre-cut into the shape of the stent and pre-loaded in the area of ​​the delivery device. The sheet of material can be cut using a trephine device at the time of implantation.

[0255] In one embodiment, the sheet of material 101 can be manually loaded through the cutout window 326 of the outer tube 318, wherein the pusher 320 in the lumen 328 of the outer tube 318 is fully retracted in the proximal position. Once the sheet of material 101 is loaded into the delivery device 110, the shaft 310 and the sheet of material 101 can be loaded into the trephine box 205. The cover 314 of the trephine box 205 can be removed from the base 324, exposing the recess 321 of the base 324. The shaft 310 of the delivery device 110 is positioned within the slots 332, 334 so that the sheet of material 101 is positioned therebetween within the recess 321.

[0256] The cover 314 of the trephine box 205 is replaced onto the base 324, thereby compressing and / or tensioning the sheet of material 101 within the trephine box 205 in the closed configuration. The cutting member 312 can be inserted through the hole 338 of the cover 314, thereby pushing the blade 344 through the cover 314 toward the sheet of material 101. The cutting member 312 can be positioned within the trephine box 205 so that the blade 344 of the cutting member 312 completely cuts through the sheet of material 101. With the blade 344 still in the fully cut position relative to the trephine box 205, the pusher 320 is pushed distally to prepare the shaft 310 and place the now cut stent 105 within the lumen of the outer tube 318 toward the opening from the lumen 238 near the distal-most end of the tube 318. The delivery device 110 is now ready for use with the patient.

[0257] In one embodiment, the sheet of material 101 can be loaded into the recess 1321 of the delivery device 1110. The access door 1314 can be opened and the sheet of material 101 can be placed in the recess 1321. The door 1314 can be closed, thereby capturing and at least partially compressing the sheet of material 101 in the recess 1321. The tensioner 1350 can be actuated to apply tension to the sheet of material 101 before cutting with the cutting tube 1312. The cutting tube 1312 can be actuated to slide distally to thereby cut the sheet of material 101 into the stent 105. The pusher 1320 can then be pushed distally to prepare the shaft 1310 by positioning the cut stent 105 within the distal region of the lumen 1382 of the guide tube 1380. The pusher 1320 can relax into a curved shape once it is pushed distally toward the rigid outer tube 1318, thereby prompting the guide tube 1380 to also assume this curved shape. The delivery device 110 is now ready for use with the patient. As described above, guide tube 1380 can be flexible and / or have a curved shape at its distal region that is configured to conform to the shape of the desired implantation location, such as the curvature of the eye near the anterior angle.

[0258] Typically, the stent 105 located within the shaft of the delivery device can be implanted through an unobstructed corneal or scleral incision formed using the delivery device or a device separate from the delivery device. An observation lens such as a gonioscopic lens can be positioned near the cornea. The observation lens is capable of observing the internal areas of the eye, such as scleral spurs and scleral junctions, from a position in front of the eye. The observation lens can optionally include one or more guide channels sized to receive the shaft of the delivery device. An endoscope can also be used during delivery to assist in visualization. Ultrasound guidance can also be used using a high-resolution biomicroscope, OCT, etc. Alternatively, a small endoscope can be inserted through another limbal incision in the eye to image the eye during implantation.

[0259] The distal end of the shaft holding the support 105 can penetrate the cornea (or sclera) to enter the anterior chamber. In this regard, a single incision can be made in the eye, such as within the limbus. In one embodiment, the incision is very close to the limbus, such as at the level of the limbus or within 2 mm of the limbus in a transparent cornea. The shaft can be used to form the incision, or a separate cutting device can be used. For example, a knife tip device or a diamond knife can be used to initially enter the cornea. A second device with a scraper tip can then be advanced above the knife tip, with the plane of the scraper positioned to coincide with the anatomical plane.

[0260] The corneal incision can be of a size sufficient to allow the shaft to pass through. In one embodiment, the incision size is about 1 mm. In another embodiment, the size of the incision is no greater than about 2.85 mm. In another embodiment, the incision is no greater than about 2.85 mm and greater than about 1.5 mm. It has been observed that incisions as large as 2.85 mm are self-sealing incisions.

[0261] After insertion through the incision, the shaft can be advanced into the anterior chamber along a path that enables the stent 105 to be delivered from the anterior chamber to a target location, such as the supraciliary space and / or supraciliary space. The shaft can be further advanced into the eye by positioning the shaft for access so that the farthest end of the shaft penetrates tissue at an angle to the eye, such as the iris root or the region of the ciliary body or the iris root portion of the ciliary body near its tissue boundary with the scleral spur.

[0262] The scleral spur is an anatomical landmark on the wall of the corner of the eye. The scleral spur is above the level of the iris but below the level of the trabecular meshwork. In some eyes, the scleral spur may be masked by the lower band of the pigmented trabecular meshwork and is directly behind it. The axis can travel along a path toward the corner of the eye and the scleral spur so that the axis passes near the scleral spur on the way to the supraciliary space, but does not necessarily penetrate the scleral spur during delivery. Instead, the axis can be close to the scleral spur and move downward to dissect the tissue boundary between the sclera and the ciliary body, with the dissecting entry point starting below the scleral spur at the root of the iris adjacent to the root of the iris or the ciliary body. In another embodiment, the delivery path of the implant intersects the scleral spur.

[0263] The axis can approach the corner of the eye from the same side of the anterior chamber as the deployment position, so that the axis does not have to be advanced through the iris. Alternatively, the axis can approach the corner of the eye from passing through the anterior chamber AC, so that the axis is advanced through the iris and / or anterior chamber toward the opposite side of the corner of the eye. The axis can approach the corner of the eye along various paths. The axis does not necessarily pass through the eye and does not intersect with the central axis of the eye. In other words, when looking at the eye along the optical axis, the corneal incision and the position where the bracket 105 is implanted in the corner of the eye can be in the same quadrant. In addition, the path of the bracket 105 from the corneal incision to the corner of the eye should not pass through the center line of the eye to avoid interfering with the pupil.

[0264] The shaft can be continuously advanced into the eye, for example, by about 6 mm. The dissection plane of the shaft can follow the curve of the inner scleral wall, so that the stent 105 mounted in the shaft, for example, after penetrating the iris root or the iris root portion of the ciliary body CB, can bluntly dissect the boundary between the tissue layers of the scleral spur and the ciliary body CB, so that the distal region of the stent 105 extends through the ciliary body space and is then further positioned between the tissue boundaries of the sclera and choroid forming the suprachoroidal space.

[0265] Once properly positioned, the stent 105 can be released. In some embodiments, the stent 105 can be released by withdrawing the outer tube 318 of the shaft 310 while the pusher 320 prevents the stent 105 from being withdrawn along with the outer tube 318. In other embodiments, the stent 105 can be released by withdrawing the guide tube 1380 while the pusher 1320 remains fixed, as described elsewhere herein.

[0266] Once implanted, the stent 105 forms a fluid communication path between the anterior chamber and the target path (e.g., the supraciliary space or the supraciliary space). As described above, the stent 105 is not limited to implantation in the supraciliary space or the supraciliary space. The stent 105 can be implanted in other locations that provide fluid communication between the anterior chamber and various locations in the eye, such as Schlemm's canal or a subconjunctival location of the eye. In another embodiment, the stent 105 is implanted to form a fluid communication path between the anterior chamber and Schlemm's canal and / or a communication path between the anterior chamber and the subconjunctival location of the eye. It should be understood that the device described herein can also be used for delivering the stent through the sclera and delivering the stent from the internal path.

[0267] As described above, the material used to form the scaffold may be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

[0268] The scaffolds described herein can be used to prevent or treat a variety of systemic and ocular conditions, such as inflammation, infection, cancerous growth. More specifically, eye diseases such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, herpes simplex virus and adenovirus infection can be treated or prevented.

[0269] The following classes of drugs can be delivered using the device of the present invention: antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport / mobility inhibitors, such as colchicine, vincristine, cytochalasin B and related compounds; anti-glaucoma drugs including beta-blockers such as timolol, betaxolol, atenolol and prostaglandin analogs such as bimatoprost, travoprost, latanoprost, etc.; carbonic anhydrase inhibitors, such as acetazolamide, methazolamide, dichlorphenamide, acetazolamide; and neuroprotectants, such as nimodipine and related compounds. Additional examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; antibacterials such as sulfonamides, sulfacetamide, sulfadimethoxazole, and sulfisoxazole; antifungals such as fluconazole, nitrofuracil, amphotericin B, ketoconazole, and related compounds; antivirals such as trifluridine, acyclovir, ganciclovir, DDI, AZT, foscarnet, adenosine, trifluridine, idoxuridine, ribavirin, protease inhibitors, and anti-cytomegalovirus agents; antiallergics such as methapyrine; chlorpheniramine, pyridoxine, and chlorpheniramine. Lamine and phenpyridine; anti-inflammatory agents such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, flumethasone, betamethasone and triamcinolone; decongestants such as phenylephrine, naphazoline and tetrahydrazide; miotics and anticholinesterases such as pilocarpine, carbachol, diisopropyl fluorophosphate, iodine and desmoline bromide; mydriatics such as atropine sulfate, cyclopentolone, homatropine, scopolamine, tocatropine, euctropine; sympathomimetics such as epinephrine and vasoconstrictors and vasodilators; ranibizumab, bevacizumab and triamcinolone.

[0270] Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, such as AT-100, available from Bayer AG, Leverkusen, Germany) can also be delivered. Ibuprofen, such as from Leverkusen, Germany Wyeth, Collegeville, Pa.; indomethacin; mefenamic acid), COX-2 inhibitors (from Pharmacia Corp., Peapack, NJ COX-1 inhibitors), including prodrugs Immunosuppressants, such as sirolimus ( from Wyeth, Collegeville, PA), or matrix metalloproteinase (MMP) inhibitors that act early in the inflammatory response pathway (e.g., tetracycline and tetracycline derivatives). Anticoagulants such as heparin, antifibrinogen, fibrinolysin, anticoagulant activator, etc. can also be delivered.

[0271] Antidiabetic agents that can be delivered using the present device include acethexamide, chlorsulfonylurea, glipizide, glyburide, tolazoamide, tolbutamide, insulin, aldose reductase inhibitors, and the like. Some examples of anticancer agents include 5-fluorouracil, doxorubicin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, estramustine, etoposide, evagonist, filgrastim, floxuridine, fludarabine, fluorouracil, fluoxymesterone, flutamide, goserelin, isosulfonylurea, leuprolide, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, pentostatin, pipobroman, plicamycin, procarbazine, sagamustine, streptozocin, tamoxifen, paclitaxel, teniposide, thioguanine, uracil mustard, vinblastine, vincristine, and vindesine.

[0272] The device can be used to deliver hormones, peptides, nucleic acids, carbohydrates, lipids, glycolipids, glycoproteins and other macromolecules. Examples include: endocrine hormones such as pituitary, insulin, insulin-related growth factor, thyroid, growth hormone; heat shock proteins; immune response modifiers, such as muramyl dipeptide, cyclosporin, interferon (including α, β and γ interferon), interleukin 2, cytokines, FK506 (an epoxy-pyrido-oxazole ring tricosinone, also known as tacrolimus), tumor necrosis factor, pentostatin, thymopentin, transforming factor β, erythropoietin; anti-tumor production proteins (e.g., anti-vascular endothelial growth factor, interferon), etc. and anticoagulants, including anticoagulant activating enzymes. Other examples of macromolecules that can be delivered include monoclonal antibodies, brain nerve growth factor (BNGF), brain nerve growth factor (CNGF), vascular endothelial growth factor (VEGF) and monoclonal antibodies against these growth factors. Other examples of immunomodulators include tumor necrosis factor inhibitors, such as thalidomide.

[0273] In various embodiments, description is made with reference to the accompanying drawings. However, certain embodiments may be implemented without one or more of these specific details, or in combination with other known methods and configurations. In the description, many specific details, such as specific configurations, dimensions and processes, are set forth in order to provide a thorough understanding of the embodiments. In other cases, well-known processes and manufacturing techniques are not particularly described in detail to avoid unnecessary confusion in the description. References to "one embodiment", "embodiment", "one implementation", "implementation", etc. throughout the specification mean that the specific features, structures, configurations or characteristics described are included in at least one embodiment or implementation. Therefore, the phrases "one embodiment", "embodiment", "one implementation", "implementation", etc. that appear in different places throughout this specification do not necessarily refer to the same embodiment or implementation. In addition, specific features, structures, configurations or characteristics can be combined in any suitable manner in one or more embodiments.

[0274] Relative terms are used throughout the description to indicate relative positions or directions. For example, "distal" may indicate a first direction away from a reference point. Similarly, "proximal" may indicate a position in a second direction opposite to the first direction. The reference point used here may be an operator, so that the terms "proximal" and "distal" refer to the operator using the device. The region of the device closer to the operator may be described as "proximal" in this article, and the region of the device farther from the operator may be described as "distal" in this article. Similarly, the terms "proximal" and "distal" may also be used herein to refer to the anatomical position of the 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. Therefore, the position of the proximal side may mean a position in the patient closer to the entry point of the device along the insertion path toward the target, and the position of the distal end may mean a position in the patient farther away from the entry point of the device along the insertion path toward the target position. However, these terms are provided to establish a relative reference system, rather than to limit the use or orientation of the device to the specific configuration described in various embodiments.

[0275] Although this specification contains many details, these should not be interpreted as limitations on the scope of what is claimed or may be claimed, but rather as descriptions of specific features of specific embodiments. Certain features described in the context of a single embodiment in this specification may also be implemented in combination in a single embodiment. On the contrary, the various features described in the context of a single embodiment may also be implemented in multiple embodiments individually or in any suitable sub-combination. In addition, although features may be described above as working in certain combinations and even initially claimed, one or more features may be removed from the claimed combination in some cases, and the claimed combination may be for a sub-combination or a variant of a sub-combination. Similarly, although operations are depicted in a particular order in the accompanying drawings, this should not be understood as requiring these operations to be performed in the particular order shown or in sequence, or requiring the execution of all illustrated operations to obtain the desired result. Only a few examples and implementations are disclosed. The described examples and implementations and other implementations may be varied, modified, and enhanced based on what is disclosed.

[0276] In the above description and claims, phrases such as "at least one" or "one or more" may appear after a connected list of elements or features. The term "and / or" may also appear in a list of two or more elements or features. Unless there is other implicit or explicit contradiction with the context in which it is used, such a phrase is intended to represent any element or feature listed separately or any combination of a referenced element or feature with any other referenced element or feature. For example, the phrases "at least one of A and B;" "one or more of A and B;" and "A and / or B" are each intended to represent "single A, single B, or A and B together". A similar explanation also applies to a list containing three or more items. For example, the phrases "at least one of A, B, and C;" "one or more of A, B, and C;" "A, B, and / or C" each mean "single A, single B, single C, A and B together, A and C together, B and C together, or A and B and C together".

[0277] Use of the term "based on" above and in the claims is intended to mean "based, at least in part, on" such that unrecited features or elements are also allowable.

[0278] The systems disclosed herein can be packaged together in a single package. The finished package will be sterilized using a sterilization method such as ethylene oxide or radiation, labeled and boxed. Instructions for use can also be provided inside the box or via an Internet link printed on the label.

Claims

1. A stent having a first end and a second opposite end, the stent having no internal lumen, wherein: The first end is configured to be positioned within an anterior chamber of an eye and the second opposing end is configured to be positioned within Schlemm's canal of the eye to form a fluid communication path between the anterior chamber and Schlemm's canal.

2. The bracket according to claim 1, wherein: The scaffold comprises a biologically derived material.

3. The bracket according to claim 2, wherein: The biologically derived material includes tissue collected from a donor or from the eye.

4. The bracket according to claim 2, wherein: The biologically derived material is an autograft, allograft or xenograft material.

5. The bracket according to claim 1, wherein: The scaffold is an engineered tissue.

6. The bracket according to claim 5, wherein: The engineered tissue is a 3D printed material suitable for implantation.

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