HK40120896A - Stent - Google Patents

Description

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This application is a divisional application of PCT international invention patent application No. 202080057488.5, filed on January 30, 2020, entitled "Implantable biological scaffold and system for molding and preparing biomaterials for the treatment of glaucoma".

Cross-references to related applications

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

Technical Field

This application relates to implantable biological scaffolds and systems for molding and preparing biomaterials for the treatment of glaucoma.

Background Technology

The main focus of glaucoma ophthalmic surgery is to enhance aqueous humor outflow. There are several approaches to this type of surgery, including: 1) lateral trabeculectomy or shunt, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a transscleral outflow path; 2) medial trabeculectomy or transscleral outflow stent placement or shunt using hardware-based implantable devices or ablation-based, non-implantable cutters (such as double-blade and trabeculectomy devices); and 3) endoscopic supraciliary stent placement using implantable non-biological hardware implants.

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

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

Summary of the Invention

Methods and apparatus for reducing, adjusting, or otherwise regulating intraocular pressure by implanting a minimally invasive biological tissue scaffold in the eye are disclosed. In an example embodiment, a biological tissue implant, such as a biological tissue scaffold, shunt, or implant, is implanted in the eye such that the scaffold is at least partially positioned on the choroid, transscleral, and/or supraciliary body sites within the eye for the treatment of glaucoma. The scaffold can be implanted in the eye via an internal delivery pathway using a delivery device configured for such a delivery pathway. In an example embodiment, the scaffold assists or otherwise provides a uveal-scleral outflow pathway for aqueous humor drainage from the anterior chamber to the eye. The scaffold provides a fluid channel between the anterior chamber and the suprachoroidal and/or supraciliary body spaces. The scaffold provides the fluid channel/outflow in two independent but cooperative manner, for example, by scaffold implantation into the supraciliary body slit and by using a hydrophilic biomaterial that allows exudative water flow through the material itself. Other drainage pathways are also contemplated, including Schrem's canal or via a subconjunctival location.

In one aspect, a system is provided for preparing an implant and inserting the implant into an eye via an intraocular approach. The system includes a handle having one or more actuators; and an elongated shaft extending distally from the handle. 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 relative to the handle and the recess to a cutting configuration. As the cutting member moves toward the cutting configuration, it cuts the sheet of material into an implant. Once cut, the implant is axially aligned with the lumen of the tubular outer sheath. The inner elongated member is movable relative to the tubular outer sheath to advance the implant to a deployment position within the lumen of the tubular outer sheath for delivery into the eye.

The material sheet may include bio-derived materials suitable for transplantation into the eye. The bio-derived material may include tissue harvested from a donor or the eye. The bio-derived material may be autologous, allogeneic, or xenograft material. The material may be engineered tissue. The engineered tissue may be a 3D-printed material suitable for implantation. The bio-derived material may have a permeable and/or robust structure, allowing water to drain from the eye when the implant, cut from the material sheet, is positioned within the ciliary body detachment slit. The implant, cut from the material sheet, may be bioresorbable or non-bioresorbable.

Implants may include one or more therapeutic agents. One or more therapeutic agents may include antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport/migration inhibitors, antiglaucoma drugs, prostaglandin analogs, carbonic anhydrase inhibitors, neuroprotective agents, antibiotics, antiviral agents, antiallergic agents, anti-inflammatory agents, mydriatics, or immunomodulators.

Before the cutting member moves to the cutting configuration, the material sheet can be compressed and/or tensioned. The material sheet can be compressed between two juxtaposed planar surfaces to prevent movement during subsequent cutting of the material sheet by the cutting member. The material sheet can be tensioned by a pair of flexible tensioner legs configured to apply a tensile force away from the centerline of the material sheet.

The system may also include a housing detachably coupled to a region of the handle. The housing may include a base and a cover. A recess may be positioned within the base of the housing. 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 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 within the recess on either side of the protrusion. The protrusion may push the centerline of the material sheet upward toward the door. When the access door is rotated relative to the handle to a closed configuration, the material sheet may be trapped between the protrusion and the access door. The access door may be configured to apply tension to the material sheet 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 tensioner legs configured to extend into the recess. The pair of flexible tensioner legs may cover a first foot of the material sheet on a first side of the centerline and a opposite foot of the material sheet on the opposite side of the centerline. When the pair of stretcher legs are further pushed into the recess by the actuator that stretches the material sheet relative to the center line, the first foot and the opposite foot are pushed outward from each other.

At least the proximal portion of the slender shaft may extend along the longitudinal axis. The distal region of the slender shaft may be angled to the longitudinal axis. The distal region of the slender shaft may have a maximum outer diameter not exceeding about 1.3 mm. The distal end of the slender shaft may be blunt to allow dissection between ocular tissues without cutting tissue. The tubular outer sheath may be a hypotube with an inner diameter less than about 0.036” to about 0.009”. The implant cut from the sheet of material may have dimensions that substantially fill the inner diameter of the tubular outer sheath.

A tubular outer sheath may be coupled to a first actuator, and an inner elongated member may be coupled to a second actuator. The first actuator may be located on the lower surface of the handle and is configured to retract the tubular outer sheath proximally, and the second actuator may be located on the upper surface of the handle and is configured to advance the inner elongated member distally. Distal advancement of the inner elongated member can propel the implant distally through the lumen of the tubular outer sheath into a preparatory position near the distal opening of the lumen of the tubular outer sheath. Proximal retraction of the tubular outer sheath while the inner elongated member remains stationary relative to the handle can disengage the implant from the elongated axis for deployment within the eye.

The tubular outer sheath can be a guide tube that is movable through the inner cavity of a fixed outer tube. An inner elongated member can move within the guide tube. The guide tube can be more flexible than the inner elongated member, and the inner elongated member can be more flexible than the fixed outer tube. The inner elongated member can take on the shape of the fixed outer tube when retracted proximally and relax back to a curved shape when extending distally out of the outer tube. When both the guide tube and the inner elongated member extend distally out of the outer tube, the guide tube can conform to the curved shape of the inner elongated member.

In an interconnected aspect, a cassette is provided for use with a system for preparing an implant and inserting the implant into an intraocular cavity of the eye. The cassette includes a base having an upper surface defining a recess, the size and shape of which are designed to receive a sheet of material to be cut into an implant. The cassette includes a lid movably coupled to the base between an open configuration and a closed configuration. The lid has a lower surface that, when in the closed configuration, is arranged juxtaposed with the upper surface of the base. The cassette includes a cutting member movable relative to the base and the recess into a cutting configuration. As the cutting member moves toward the cutting configuration, it cuts the sheet of material into an implant. Once cut, the implant is axially aligned with the inner lumen of a tubular outer sheath for delivery into the eye.

When the cover is in the closed configuration, the material sheet can remain fixed relative to the base. When the cover is in the closed configuration, the material sheet can be compressed within the recess. The cover can be configured to apply tension to the material sheet compressed within the recess.

In an interconnected aspect, a method is provided for preparing an implant for implantation in a patient's eye and for inserting the implant into the patient's eye. The method includes inserting a sheet of material into a proximal portion of an instrument. The instrument also includes a cutting member sized and designed for insertion into a distal portion of 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 within 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 locating the distal portion adjacent to ocular tissue and deploying the implant from the instrument.

The insertion of a material sheet may include inserting the sheet into a recess in a proximal portion and closing a cap over the recess. The cap may be adapted to engage at least a portion of the material sheet prior to cutting. At least a portion of the cap may be transparent. The cap may prevent the sheet from moving during cutting with a cutting member. The method may also include tensioning at least a portion of the material sheet prior to cutting. This tensioning portion may include a first and second portion of the compression sheet and a central portion of the tensioning sheet, the central portion being located between the first and second portions. The central portion of the sheet may include an implant when the sheet is cut with a cutting member. This tensioning portion may include an activation actuator to tension this portion of the sheet. Activating the actuator may include a rotational actuator to tension this portion of the sheet. The cap 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 device into the anterior chamber through an internal corneal incision, while the proximal portion of the device remains outside the eye. The material may be a bio-derived material suitable for implantation in the eye. Bio-derived materials can be tissues harvested from a donor or patient, or autologous, allogeneic, or xenograft materials. The material can be engineered or 3D-printed materials suitable for implantation. The implant may include one or more therapeutic agents.

Deploying an implant from the device results in the implant residing at least partially between the ciliary body and sclera of the patient's eye. The implant may reside within a ciliary body detachment gap between the ciliary body and 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 piece of material and capture the implant within the cutting member lumen. The pair of opposing cutting edges may cut the piece in two locations to separate the implant from the remainder of the piece. 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. As the cutting member completes the cutting of the piece to form the implant, the longitudinal axis of the implant may remain aligned with the longitudinal axis of the elongated tubular member lumen.

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

Positioning the distal portion adjacent to ocular tissue may include positioning the implant between the ciliary body and the sclera, with the implant at least partially remaining within the lumen of the distal portion. Deploying the implant from the instrument may include retracting the elongated tubular portion of the implant while maintaining the implant's position relative to adjacent ocular tissue. The distal end of the elongated tubular member may be blunt to allow dissection of ocular tissue without cutting it. Closing the cap over the recess may include engaging a portion of the cap with a first portion of the sheet to compress the first portion of the sheet and tension a second portion of the sheet.

This disclosure also discloses the following items:

1. A system for preparing an implant and inserting the implant into an eye via an intraocular approach, the system comprising:

Handles including one or more actuators;

An elongated shaft extending distally from the handle, the elongated shaft comprising a tubular outer sheath and an inner elongated member located within the inner cavity of the tubular outer sheath;

The size is designed to hold the material sheet fixed relative to the handle in a recess;

A cutting member that can be moved relative to the handle and the recess into a cutting configuration.

As the cutting member moves toward the cutting configuration, it cuts the material sheet into an implant, and the implant, once cut, is axially aligned with the inner cavity of the tubular outer sheath. Furthermore, the inner elongated member is movable relative to the tubular outer sheath to advance the implant to a deployment position within the inner cavity of the tubular outer sheath for delivery into the eye.

2. The system according to Project 1, wherein the material sheet comprises a bio-derived material suitable for transplantation into the eye.

3. The system according to Project 2, wherein the bio-derived material comprises tissue collected from a donor or from the eye.

4. The system according to Project 2, wherein the bio-derived material is an autologous graft, an allogeneic graft, or a xenograft material.

5. The system according to Project 1, wherein the material is an engineered organization.

6. The system according to Project 5, wherein the engineered tissue is a 3D printing material suitable for implantation.

7. The system according to Item 2, wherein the bio-derived material has a permeable and/or robust structure, thereby allowing water to drain from the eye when the implant, cut from the material sheet, is positioned within the ciliary body dislocation slit.

8. The system according to Project 1, wherein the implant cut from the material sheet is bioresorbable or non-bioresorbable.

9. The system according to item 1, wherein the implant comprises one or more therapeutic agents.

10. The system according to item 9, wherein the one or more therapeutic agents include antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport/mobility inhibitors, antiglaucoma drugs, prostaglandin analogs, carbonic anhydrase inhibitors, neuroprotective agents, antibiotics, antiviral agents, antiallergic agents, anti-inflammatory agents, mydriatics, or immunomodulators.

11. The system according to Item 1, wherein the material sheet is compressed and/or tensioned before the cutting member moves to the cutting configuration.

12. The system according to item 1, wherein the material sheet is compressed between two juxtaposed planar surfaces to prevent movement during subsequent cutting of the material sheet with the cutting member.

13. The system according to Project 1, wherein the material sheet is tensioned by a pair of flexible tensioner legs, the flexible tensioner legs being configured to apply a tensile force away from the centerline of the material sheet.

14. The system according to item 1 further includes a housing detachably coupled to a region of the handle, the housing including a base and a cover, wherein the recess is located within the base of the housing.

15. The system according to item 1, wherein the recess is located within the handle.

16. The system according to item 11 further includes an access door coupled to the handle and configured to close the recess when rotated to a closed configuration and expose the recess when rotated to an open configuration.

17. The system according to item 16, wherein the access door is formed of a transparent or translucent material.

18. The system according to item 16 further includes 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.

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

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

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

22. The system according to item 21, wherein when the pair of stretcher legs are further pushed into the recess by an actuator that stretches the material sheet relative to the centerline, the first foot and the opposite foot are pushed outward from each other.

23. The system according to item 1, wherein at least the proximal portion of the elongated shaft extends along a longitudinal axis.

24. The system according to item 23, wherein the distal region of the elongated shaft is at an angle to the longitudinal axis.

25. The system according to Item 1, wherein the distal end of the elongated shaft is blunt to allow dissection between tissues of the eye without cutting the tissues.

26. The system according to Project 1, wherein the distal region of the elongated shaft has a maximum outer diameter of not more than about 1.3 mm.

27. The system according to Item 1, wherein the tubular outer sheath is a thiocyanate tube with an inner diameter of less than about 0.036” to about 0.009”.

28. The system according to Item 1, wherein the implant cut from the material sheet has a size that substantially fills the inner diameter of the tubular outer sheath.

29. The system according to Item 1, wherein the tubular outer sheath is coupled to a first actuator, and the inner elongated member is coupled to a second actuator.

30. The 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 elongated member distally.

31. The system according to item 29, wherein distal advancement of the inner elongated member pushes the implant distally through the lumen of the tubular outer sheath into a preparatory position near the distal opening of the lumen of the tubular outer sheath.

32. The system according to item 31, wherein, when the inner elongated member remains stationary relative to the handle, the proximal retraction of the tubular outer sheath disengages the implant from the elongated axis to deploy it within the eye.

33. The system according to Item 1, wherein the tubular outer sheath is a guide tube movable through the inner cavity of a fixed outer tube, and wherein the inner elongated member is movable within the guide tube.

34. The system according to item 33, wherein the guide tube is more flexible than the inner elongated member, and the inner elongated member is more flexible than the fixed outer tube.

35. The system according to item 33, wherein the inner elongated member takes the shape of the fixed outer tube when retracted proximally, and relaxes back to a curved shape when extending distally out of the outer tube.

36. The system according to item 35, wherein when both the guide tube and the inner elongated member extend distally out of the outer tube, the guide tube conforms to the curved shape of the inner elongated member.

37. A cartridge for use with a system for preparing an implant and inserting the implant into an eye via an intraocular approach, the cartridge comprising:

A base having an upper surface with a defined recess, the size and shape of which are designed to receive a piece of material to be cut into an implant;

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

A cutting member capable of moving relative to the base and the recess into a cutting configuration, wherein the cutting member cuts the material sheet 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.

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

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

40. The box according to item 37, wherein the lid is configured to apply tension to the material sheet compressed within the recess.

41. A method for preparing an implant for implantation in a patient's eye and inserting said implant into the patient's eye, the method comprising:

A piece of material is inserted into the proximal portion of the device, which also includes a cutting component and a portion sized for insertion into the distal portion of the eye;

The sheet is cut using a cutting component to form the implant;

The implant is advanced from the proximal portion of the device to a deployment position within the lumen of the elongated tubular member of the distal portion;

Insert the distal portion of the device into the anterior chamber of the eye;

The distal portion is located adjacent to eye tissue; and

The implant is deployed from the device.

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

43. The method according to item 42, wherein the cover is adapted to engage at least a portion of the material sheet prior to the cutting.

44. The method according to item 42, wherein at least a portion of the cover is transparent.

45. The method according to item 42, wherein the cover prevents the sheet from moving during the cutting of the sheet by the cutting member.

46. The method according to item 41 further includes tensioning at least a portion of the material sheet before cutting the material sheet.

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

48. The method of claim 47, wherein the central portion of the sheet includes the implant when the sheet is cut with the cutting member.

49. The method of claim 46, wherein tensioning the portion of the sheet includes activating an actuator to tension the portion of the sheet.

50. The method of claim 49, wherein activating the actuator includes rotating the actuator to tension the portion of the sheet.

51. The method according to item 43, wherein the cover includes an actuator, and wherein actuation of the actuator tensions at least a portion of the sheet.

52. The method of claim 41 further includes inserting the distal portion of the device into the anterior chamber via a corneal incision, while the proximal portion of the device remains outside the eye.

53. The method according to item 41, wherein the material comprises a bio-derived material suitable for implantation in the eye.

54. The method according to item 53, wherein the bio-derived material comprises tissue collected from a donor or from a patient, or autologous, allogeneic, or xenograft material.

55. The method according to item 41, wherein the material comprises engineered or 3D printed materials suitable for implantation.

56. The method according to item 41, wherein the implant comprises one or more therapeutic agents.

57. The method of claim 41, wherein deploying the implant from the device results in the implant residing at least partially between the ciliary body and sclera of the patient's eye.

58. The method according to item 57, wherein the implant is located between the ciliary body and the sclera within the ciliary body detachment slit.

59. The method of claim 41, wherein the cutting member includes a cutting member cavity, 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 cavity.

60. The method according to item 59, wherein the pair of opposing cutting edges cut the sheet at two locations to separate the implant from the remainder of the sheet.

61. The method according to item 59, wherein the inner diameter of the elongated tubular member is substantially the same as the inner diameter of the inner cavity of the cutting member.

62. The method according to item 59, wherein the distal portion of the cutting member is beveled.

63. The method according to item 41, wherein the implant includes a longitudinal axis, and wherein, when the cutting member completes cutting the piece to form the implant, the longitudinal axis of the implant remains aligned with the longitudinal axis of the lumen of the elongated tubular member.

64. The method of claim 59, wherein advancing the implant from the proximal portion of the device comprises pushing the implant out of the cavity of the cutting member and into the cavity of the elongated tubular member of the distal portion.

65. The method according to item 41, wherein the distal region of the elongated tubular member is at least one of angled, curved, or flexible.

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

Activate the first actuator before the cutting to tension at least a portion of the sheet;

After tensioning, the second actuator is activated to advance the cutting member to cut the sheet;

Activate the third actuator to advance the implant to the deployment location; and

A fourth actuator is activated to deploy the implant from the device, wherein each actuator is operatively coupled to the device.

67. The method of claim 41, wherein positioning the distal portion adjacent to ocular tissue comprises positioning the implant between the ciliary body and the sclera, wherein the implant is at least partially retained within the cavity of the distal portion.

68. The method of claim 41, wherein deploying the implant from the device includes retracting the elongated tubular portion from the implant while maintaining the position of the implant relative to adjacent ocular tissue.

69. The method according to item 41, wherein the distal end of the elongated tubular member is blunt to allow dissection of ocular tissue without cutting the ocular tissue.

70. The method according to item 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.

Details of one or more variations of the subject matter described herein are set forth in the accompanying drawings and the following description. Other features and advantages of the subject matter described herein will become apparent from the description, the accompanying drawings, and the claims.

Attached Figure Description

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

Figure 1 is a cross-sectional view of the human eye, showing the anterior and posterior chambers of the eye, with the support structure located in an example position within the eye;

Figures 2A and 2B show exemplary embodiments of a trephine drilling apparatus for forming a support;

Figure 3 shows a perspective view of an exemplary embodiment of the conveying device;

Figure 4 shows a cross-sectional view of the conveying device;

Figure 5 shows an embodiment of a conveying device having a trephine box in an open configuration;

Figure 6A illustrates an embodiment of a conveying device having a trephine box in a closed configuration;

Figure 6B is a cross-sectional view of the device in Figure 6A along line B-B;

Figure 7 shows a partial view of the delivery device shaft, which has a sheet of bio-derived material extending through a cut-out window;

Figure 8A is a top view of the cut window of the conveyor shaft;

Figure 8B is a sectional view along line B-B of Figure 8A;

Figure 9A is a perspective view of an embodiment of the trephine box;

Figure 9B is a cross-sectional view of the trephine box in Figure 9A;

Figure 9C is a perspective view of the base of the trephine box in Figure 9A;

Figure 10A is a perspective view of the trephine box of Figure 9A relative to the cutting component;

Figure 10B is a cross-sectional view of the trephine box of Figure 10A, with the cutting component partially inserted;

Figure 10C is a cross-sectional view of the trephine box of Figure 10A, with the cutting component fully inserted;

Figure 11A is a side view of the cutting component of Figure 9A, showing the blade relative to the axis of the conveyor loaded with bio-derived material sheets;

Figure 11B is a perspective view of the cut component of Figure 11A, with the shell removed;

Figure 11C is a side view of the blade relative to the conveyor shaft and the cutting support;

Figure 11D shows a side view of the cutting bracket prepared inside the cavity of the conveyor shaft;

Figure 11E is a distal view of the shaft of a conveyor device having a tubular outer sheath and an inner elongated member or actuator;

Figures 12A-12B show the distal region of the conveying device;

Figure 13A is a top view of an embodiment of the conveying device;

Figure 13B is a bottom view of the conveying device in Figure 13A;

Figures 14A-14B are partial views of the conveying device in Figure 13A;

Figures 15A-15C are schematic diagrams of tensioners that apply tension to a sheet of material;

Figures 16A-16B are schematic diagrams of cutting material sheets using a cutting tube;

Figures 17A-17B are schematic diagrams of the pusher preparing the cutting bracket in the conveyor shaft;

Figure 18A is a top view of an embodiment of the conveying device;

Figure 18B is a bottom view of the conveying device in Figure 18A;

Figures 19A-19B are partial views of the conveying device in Figure 18A;

Figures 20A-20C show a tensioner configured to apply tension to a sheet of material;

Figure 21 is a cross-sectional view of the conveying device of Figure 18A, showing the tensioner;

Figure 22 is a partial view of the cutting tube being propelled through the device in Figure 18A;

Figures 23A-23D are detailed partial views of the cut tube in Figure 22;

Figures 24A-24C are partial cross-sectional views of the cutting bracket released from the conveyor shaft of Figure 18A;

Figure 25 is a partial cross-sectional view showing the propulsion mechanism for the various axially movable parts of the device in Figure 18A;

Figure 26 is a partial cross-sectional view of the retraction mechanism of the guide tube for the device of Figure 18A.

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

Detailed Implementation

Implants, systems, and methods for increasing water outflow from the anterior chamber are disclosed. As will be described in detail below, endovascular outflow stent implantation using biological, cell-based, or tissue-based materials provides enhanced biocompatible water outflow with improved tolerability and safety compared to conventional shunts. In example embodiments, biological tissue or bio-derived material, also referred to herein as a stent, is harvested or generated in vitro using a trephine device or cutting tool. In one embodiment, the stent is an elongated body or tissue strip without an internal lumen. Lumen-based devices may be limited by the lumen acting as a fibrotic occlusion pathway. The stent formed from this tissue is then implanted into the eye via an endovascular delivery pathway to provide water outflow from the anterior chamber. The stents described herein can be used as phacoemulsification-assisted or stand-alone treatment for glaucoma, as part of minimally invasive glaucoma surgery (MIGS).

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

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

The term "bio-derived material" includes naturally occurring biomaterials and synthetic biomaterials and combinations thereof suitable for implantation in the eye. Bio-derived materials include materials that are natural biological structures having a biological arrangement naturally present in a mammalian subject, including organs or organ portions formed from tissue, and tissues formed from materials grouped together according to structure and function. Bio-derived materials include tissues such as corneal, scleral, or cartilage tissue. Tissues considered herein can include any of a variety of tissues, including muscle, epithelium, connective tissue, and neural tissue. Bio-derived materials include tissues, organs, organ portions, and tissues from a subject harvested from a donor or patient, including tissue blocks suitable for transplantation, including autologous, allogeneic, and xenograft materials. Bio-derived materials include naturally occurring biomaterials, including any material naturally present in a mammalian body. As used herein, bio-derived materials also include materials engineered to have a biological arrangement similar to a natural biological structure. For example, such materials can be synthesized using in vitro techniques, such as by seeding 3D scaffolds or matrices with appropriate cells, engineering or 3D printing materials to form a bioconstruct suitable for implantation. Bio-derived materials used in this article also include cell-derived materials, including stem cell-derived materials.

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. Biological tissue can be hydrophilic or hydrophobic. Biological tissue may include or be impregnated with one or more therapeutic agents for additional ophthalmic treatment procedures.

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

Regardless of the source or type of the biologically derived material, it can be cut or trephinated into an elongated shape suitable for stent implantation and placement in the eye. This trephination process can be performed on the tissue before or during the surgical implantation procedure. The stent in the eye may have a structure and/or permeability that allows aqueous humor to flow out of the anterior chamber when positioned within the ciliary body detachment slit.

Figure 1 is a cross-sectional view of the human eye, showing the anterior chamber AC and the posterior chamber PC. The stent 105 can be positioned at an intraocular implantation site such that at least a first portion of the stent 105 is positioned within the anterior chamber AC and a second portion of the stent 105 is positioned within tissue, such as within the supraciliary space and/or the suprachoroidal space of the eye. The size and shape of the stent 105 are designed to allow it to be positioned in such a configuration. The stent 105 provides or otherwise serves as a channel for aqueous humor to flow away from the anterior chamber AC (e.g., to the supraciliary space and/or the suprachoroidal space). In Figure 1, the stent 105 is schematically shown as an elongated body. It should be understood that the size and shape of the stent 105 can vary.

The stent 105 can be implanted via an internal approach, for example, through a patent corneal or scleral incision. The stent can be implanted to create communication between the anterior chamber AC and the supraciliary space, the anterior chamber AC and the suprachoroidal space, the anterior chamber AC and Schrem's canal, or the anterior chamber AC and the subconjunctival space. In a preferred embodiment, the stent 105 is implanted such that its distal end is positioned within the supraciliary location and its proximal end is positioned within the anterior chamber AC to provide a supraciliary slit. The distal end of the stent 105 can be positioned between other anatomical parts of the eye.

Conventional glaucoma stent implantation 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 material described in this article can reduce and/or eliminate the risk of these tissue damages while still providing enhanced aqueous humor outflow.

The scaffold 105 described herein can be formed from any of a variety of bio-derived materials having permeability and/or structures that allow water filtration through it. The scaffold 105 can be formed from bio-derived materials that are harvested, engineered, grown, or otherwise manufactured. The bio-derived scaffold material can be obtained or harvested from a patient or donor. The bio-derived scaffold material can be harvested before or during surgery. The bio-derived scaffold material can be synthetic biological tissue generated using in vitro techniques. The bio-derived material can be stem cell-derived or bioengineered. The tissue can be generated through in situ cellular or non-cellular growth. In an example embodiment, the tissue can be 3D printed during manufacturing.

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

In an example embodiment, the scaffold 105 is made of biological tissue. The bio-derived material can be corneal tissue and/or non-corneal tissue. The bio-derived material may include corneal, scleral, collagen, or cartilage tissue. In one embodiment, the bio-derived scaffold material may be bare corneal stroma tissue without epithelium and endothelium, which is porous and hydrophilic to allow water filtration. The bio-derived material of the scaffold 105 may, but does not necessarily, integrate into the inherent anatomy of the eye after placement. The scaffold can allow surrounding tissue to form a long-term, open pathway, even after scaffold absorption. The bio-derived scaffold material may not be significantly absorbed or integrated into the anatomy of the eye, allowing the scaffold 105 to remain implanted long-term or indefinitely as needed.

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

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

Typically, bio-derived scaffold materials possess a certain degree of rigidity, allowing them to maintain outflow from the anterior chamber; however, their rigidity is lower than that of conventional non-bio-derived polyimide shunts used in glaucoma treatment (e.g., Cypass, Alcon). The scaffold material can have sufficient structure to act as a spacer to support sustained outflow through the ciliary body. Once implanted within the ciliary detachment, the scaffold material can maintain its structural height or thickness, thus providing fluid flow through or around the scaffold. Compared to conventional non-bio-based materials such as polyimide, bio-derived scaffold materials offer advantages in biocompatibility, anatomical consistency, and water permeability. Bio-derived scaffold materials can provide better compliance and conformity to the scleral wall, and a lower likelihood of endothelial and scleral erosion/loss over time due to chronic eye friction and blinking.

In one embodiment, the material for forming the scaffold is provided as an uncut sheet of material configured to be manually loaded into the delivery device upon implantation. In other embodiments, the bio-derived material for forming the scaffold is provided as an uncut sheet pre-loaded within the shaft of the delivery device and held within the trephine device 205 or a cassette. In a further embodiment, the scaffold 105 has been cut to the shape of a scaffold pre-loaded within the shaft 310 of the delivery device or within a cassette configured to be loaded together with the delivery device. The device portion carrying the bio-derived scaffold material (whether pre-cut to scaffold size 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 solution for the bio-derived material. 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 being attached to the trephine device or delivery device at the surgical site.

After obtaining and preparing suitable materials, a slender scaffold of predetermined size can be produced from the material sheet using a trephine apparatus. As will be discussed in more detail below, trephineing can be performed during or before surgery. In some embodiments, the scaffold is formed by 3D printing and can be printed to the desired final size for use as a scaffold, or it can be printed as a material sheet and then trephineed during or before surgery. Trephineing achieved with the apparatus described herein produces a very thin strip of material that can be implanted into the eye to provide regulation of water outflow. The achieved trephine positions the cut implant within the conduit or lumen of the delivery device, allowing the cut implant to be subsequently delivered from the delivery device without removing or transferring the cut implant from the cutting element into the delivery tube. The trephineing process can simultaneously or in a subsequent actuation load the cut implant into the delivery tube for implantation into the eye.

As used herein, the term "material sheet" refers to a bio-derived material sheet whose size along at least one dimension is larger than the size of a scaffold cut from and implanted into a subject. In some embodiments, the material sheet may have a generally square shape and the scaffold trephinated from the material sheet may have a generally rectangular shape. For example, the material sheet may be approximately 7 mm wide x 7 mm long x 0.55 mm thick, and the scaffold trephinated from the material sheet may be 0.3-0.6 mm wide x 7 mm long x 0.55 mm thick. The dimensions of the material sheet and the scaffold trephinated from the material sheet can vary. The material sheet and the scaffold trephinated from the material sheet may each have the same length and the same thickness, but different widths. The material sheet and the scaffold trephinated from the material sheet may also have different lengths and thicknesses. For example, the material sheet may have a first thickness and the scaffold trephinated from the material sheet may have the same thickness, but may be folded or rolled into a thickness different from the material sheet during implantation.

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

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

The trephine apparatus described herein provides accurate and precise cuts without wrinkling. The trephine apparatus can be combined with front and rear captures to keep the material to be cut fixed in the z-plane, preventing movement before the tissue engages with the cutter. In embodiments described in more detail below, the material to be cut is held fixed, compressed, and/or tensioned prior to cutting.

Figures 2A and 2B illustrate exemplary embodiments of the trephine device 205. The intraoperative trephine device for forming a stent can be combined with or removably coupled to a delivery device, such as an applicator/syringe for delivery to the implantation site. Figures 3-4, 13A-13B, and 18A-18B illustrate embodiments of a trephine device integrated with a delivery device. As shown in Figures 5 and 6A-6B, the trephine device can be a cassette removably coupled to the delivery device. As shown in Figures 5 and 6A-6B, the cassette containing the material sheet can be coupled to the distal portion of the delivery device. In this embodiment, the cassette can be removed from the delivery device before the stent is deployed to the eye. Alternatively, the cassette containing the material sheet can be coupled to the proximal portion of the delivery device. In this embodiment, it is not necessary to remove the cassette before the stent is delivered to the eye, and the stent cut from the material sheet can be deployed from the cassette coupled to the delivery device without a separate step.

A trephine apparatus is configured to cut or otherwise shape a bio-derived tissue or material sheet having a first profile or shape (e.g., a wider square sheet or strip of material) into a second profile or shape (e.g., a narrower rectangular strip of material) conforming to an implantable scaffold having the dimensions described herein. Cuttings performed using the trephine apparatus described herein can involve guillotine, punching, rotating, sliding, rolling, or pivoting blade cutting movements. In some embodiments, cutting is performed perpendicular to a plane of the material sheet. In some embodiments, cutting is performed axially along the implanted catheter. Thus, the axis of the trephine can be aligned with, within, or parallel to the implanted catheter to allow unobstructed tissue loading and transfer for implantation without manipulating, tearing, or damaging the fragile scaffold tissue. A tissue fixation step may precede the trephineing process, wherein the bio-derived tissue forming the scaffold is securely fixed between two juxtaposed planar surfaces to ensure the tissue is not wrinkled or deformed, and that the subsequent trephine cuts are dimensionally accurate. Fixation may optionally provide tension or stretching of the tissue in at least one plane to ensure clean cuts through the tissue.

The trephine can be performed along or within a path or conduit formed within a structure, such as within a cassette, delivery device, or any other structure. The trephine of the material sheet can simultaneously or subsequently position or align the implant within a conduit (e.g., the lumen of a delivery shaft) such that the cut implant can be delivered to the eye through the conduit without needing to be transferred to a separate delivery device. In some embodiments, the cutting movement can be performed from above the material sheet, such that the sharp edge of the blade cuts the material sheet from its upper surface. As the cutter slides over the material sheet forming the implant, it can then push the cut implant downwards along an axis orthogonal to the longitudinal axis A of the handle into the lumen of the delivery shaft. In other embodiments, the cutting movement can slide along the longitudinal axis A of the handle from the proximal end of the handle 305 toward the distal end through the material sheet. The cutting movement can result in the cut implant being correctly positioned and/or aligned with the delivery conduit of the delivery shaft. The cutting member can be movable relative to the handle and relative to the recess that holds the material sheet in the cutting configuration. As the cutting component moves toward the cutting configuration, it can cut the material sheet held and fixed in the recess to form an implant, and once the implant is cut, it can be axially aligned with the tube for delivery.

Methods for preparing an implant for implantation and insertion 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 sized for insertion into the eye. Cutting the sheet with the cutting member can form an implant. 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 lumen of the cutting member that cuts the implant.

The implant can then be advanced from the proximal portion of the device to a deployment position within the lumen of the elongated tubular member of the distal portion of the device. The distal portion of the device can be inserted into the anterior chamber of the eye, thereby allowing it to be positioned within adjacent ocular tissues, where the implant is deployed from the device into the ocular tissues. For example, the distal portion of the device can be inserted into the anterior chamber via an intracorneal incision, while the proximal portion of the device remains outside the eye. It should be understood that the distal portion of the device can be used for other delivery pathways (e.g., transscleral delivery). Deploying the implant into the ocular tissues can include the implant residing at least partially between the ciliary body and sclera of the eye. The implant can reside within the ciliary body detachment space between the ciliary body and sclera.

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

Preferably, the structure is trephine-tuned in such a way 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 in place and the catheter is withdrawn from the stent, leaving the stent implanted in the eye. The catheter may be incorporated into or coupled to a delivery device for implanting and deploying the stent into the eye. The trephine device may be made of any of a variety of materials, such as rigid materials including plastics and/or metals.

The trephine device 205 shown in Figures 2A-2B may have an internal cavity or housing 210, the size and shape of which are designed to form an elongated profile of the scaffold 105 when the tissue is positioned within the housing 210. The housing 210 has dimensions approximating the size of the scaffold 105 to be formed in the micrometer range. The trephine device 205 is configured to stabilize the tissue during trephineing. In this respect, the trephine device 205 can hold the tissue in place and prevent the tissue from moving relative to the trephine device 205 during trephineing. In one embodiment, the trephine device 205 may have one or more wings 215 configured to hinge between an open (Figure 2A) and a closed (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 may be positioned on the inner surface of the wings 215 such that when the wings 215 are hinged to the closed configuration and the sheet of material is positioned within the housing 210, the sheet is cut into a scaffold of the desired size.

The housing 210 of the trephine device 205 can be converted to and/or include 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 trephines or cuts tissue along a delivery path aligned or coaxial with the stent's entry into the implantation site. For example, a stent cut from a sheet of material held within the housing 210 can be pushed distally into the delivery device axis through a lumen extending through the front end 222 of the trephine device 205. Thus, the stent can be trephineed first using a separate trephine device. The trephine device holding the stent can then be loaded into a delivery device designed to receive the trephine device. This allows for stent loading and deployment without removing the stent from the trephine device to load it into the delivery device.

The following section will describe the trephine of the support material in more detail.

Referring again to 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 via the internal delivery path. The delivery device 110 is schematically shown in 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 the internal delivery path.

The delivery device described herein can prepare an implant and perform endoscopic insertion of the implant into the eye. Figure 3 shows a perspective view of an example embodiment of the delivery device 110 with an integrated trephine. Figure 4 shows a cross-sectional view of the delivery device 110 of Figure 3. The delivery device 110 may include a proximal handle 305, sized and shaped to be gripped by a user with one hand. One or more actuators 315 may be positioned on the area of the handle 305. The actuators 315 may also be manipulated by a user with one hand, such as with the thumb or finger. The actuators 315 may be one or more of a knob, button, slider, or other interface configured to move one or more components of the delivery device 110, as will be described in more detail below.

An elongated shaft 310 (also referred to herein as an applicator or delivery body) extends distally from a handle 305. At least a portion of the shaft 310 includes or is coupled to a stent 105 for direct stent implantation. At least a portion of the shaft 310 extends along a longitudinal axis A. The shaft 310 may be angled, curved, or flexible in the distal region, thus allowing it to form a distal bend or buckle. In some embodiments, the shaft 310 may include flexible and rigid portions such that the shape of the shaft changes depending on the relative positions of these portions. The shaft 310 may be curved at least along its length and/or may be flexible.

The shaft 310 of the delivery device 110 is sized and shaped for endoscopic delivery through a patent corneal incision, allowing the stent 105 to pass through and remain within the eye from its distal end. In at least some embodiments, the distal end of the shaft 310 is sized to extend through an incision approximately 1 mm in length. In another embodiment, the distal end of the shaft 310 is sized to extend through an incision no longer than approximately 2.5 mm. In yet 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 for 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 bluntly 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 into the subconjunctival space via scleral wall dissection. In yet another embodiment, the distal end 316 may have a cutting configuration for dissection and implantation of Schrem's canal or transscleral dissection and implantation.

The stent described herein is formed as a solid strip of material without any lumen. Therefore, the stent cannot be delivered via a guidewire like many conventional glaucoma shunts. Furthermore, the stent is formed from relatively soft tissue, which is more fragile, as conventional shunts are formed from more rigid polymer or metallic materials. More rigid shunts can be implanted to create blunt dissection at the tissue interface through which the shunt is inserted, using the distal end of the shunt. The stent described herein is preferably deployed using a retractable cannula-type syringe, which can be retracted once in the appropriate anatomical position, allowing for gentler externalization and positioning of the stent. Additionally, 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 dimensions that substantially fill 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), such that the stent can be pushed distally through this portion without wrinkling or damage. The tolerance between the external dimensions of the stent 105 and the internal dimensions of the conduit can be up to approximately 200%. The catheter may also be coated with a lubricating material (e.g., Teflon) to improve the advancement of the stent 105 through the catheter during deployment.

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

Once the distal end of shaft 310 reaches the desired position in the tissue, stent 105 remains in place in the eye and shaft 310 is retracted. In one embodiment, the outer tube 318 of shaft 310 is retracted, for example, using an actuator 315 on a handle, while pusher 320 remains stationary relative to handle 305. Thus, pusher 320 can act as a stopper, preventing stent 105 from following outer tube 318 as it retracts. As a result, stent 105 is withdrawn from shaft 310 and remains within the tissue.

The conveying device 110 may also include a cutting member 312 (see FIG. 4), such as a blade or cutting tube, which is movable relative to the handle 305 to cut tissue to form a scaffold 105. As described above, the scaffold 105 may be formed from a sheet of material. The sheet of material may be loaded within the area of the conveying device 110 and cut into smaller scaffold shapes during conveying. The cutting member 312 may be actuated by a user to produce a scaffold from the sheet of material.

In an exemplary embodiment, the cutting member 312 is attached to a cover 314 (see Figures 3-4) movable relative to the handle 305. The cover 314 is coupled to a distal region of the handle 305 via a hinge 317, allowing the cover 314 to rotate relative to the handle 305 about a pivot P of the hinge 317. The cover 314 can be lifted to pivot into an open configuration (see Figure 3), exposing a recess 321 within which a sheet of material 101 can be positioned and held fixed relative to the handle. When the cover 314 rotates back to a closed configuration about the pivot P, the sheet of material 101 within the recess 321 is compressed and/or tensioned between the cover 314 and the handle 305. This compression and/or tensioning of the sheet of material 101 helps ensure a clean and complete cut of the material. In some embodiments, the sheet of material 101 is placed under tension, for example, by stretching the cover 314 outwards before cutting with the cutting member 312. The sheet of material 101 can be stretched outwards from the cutting position, as shown in Figures 15A-15C.

The recess 321 may be located within the proximal portion of the instrument, for example, together with a portion of the handle 305. The recess 321 for holding the material sheet 101 may also be a recess removably coupled to a portion of the instrument, for example, within the area of the handle 305, or within a box coupled to the distal portion of the instrument.

It should be understood that tensioning the sheet can include activating a separate actuator to tension the sheet. Tensioning can also be achieved during the stabilization and compression steps without a separate actuator. For example, simply closing cap 314 can result in compression and tension of the sheet material without a separate actuator to provide tension on the sheet material after compression.

The cover 314 can open in any of a number of orientations relative to the handle. For example, the pivot 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 pivot and the cover 314, such that the cover 314 is hinged open by rotating upward and toward the pivot (see, for example, Figures 3 and 4). Alternatively, the hinge 317 can be positioned such that the cover 314 is hinged open by rotating upward and toward the proximal region of the handle 305 (see, for example, Figures 5 and 6A-6B). In yet another embodiment, the hinge 317 can be positioned on one side of the handle 305 such that the pivot 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, for example, Figures 15A-15C). Any of a number of configurations is considered herein.

A cutting member 312 can extend from the lower surface of the cover 314 to cut a sheet of material 101 (e.g., biological tissue) in a guillotine-like manner. Figure 4 shows the cover 314 in an open configuration, raised from a recess 321, within which the sheet of material 101 is located. The cutting member 312 can extend from the lower surface of the cover 314 such that its cutting surface penetrates the sheet of material 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 an in-shelter configuration to a cutting configuration. Once the cover 314 is in a closed configuration, compressing and/or stretching the sheet of material 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 positioning 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 sheet of material 101 held within the recess 321. One of the multiple return springs 323 can push the actuator 313 upwards, causing the cutting member 312 to re-enter the sheathed configuration. As the cutting member moves toward the cutting configuration, the cutting member 312 cuts the material sheet into an implant. Once cut, the implant is also axially aligned with the inner cavity of the shaft.

It should be understood that other types of cutting mechanisms can be used. For example, the lowered cap 314 can also cut the material sheet 101 held within the recess 321 with a rotary cutting movement. In this embodiment, the cutting member 312 extends below the plane of the lower surface of the cap 314, such that a blade is available to cut the material sheet 101 when the cap 314 is rotated to the closed configuration. Alternatively, the cutting movement can be an axial cutting movement using a slidable cutting tube, causing trephination along the implantation catheter, which differs from a cutting movement perpendicular to the plane of the material sheet 101.

As described above, as the cutting member moves toward the cutting configuration, it cuts the material sheet into an implant. Once cut, the implant is also axially aligned with the inner cavity of the shaft for deployment into the eye. Therefore, the movement of the cutting member 312 simultaneously cuts the stent and positions the cut stent relative to the shaft 310, allowing the stent to be transported through the shaft 310. The cutting member 312 may include a pair of blades separated by spacers to cut the material sheet 101 into a rectangular stent shape. The spacers between the blades can engage with the cut stent 105 after the blades have cut, pushing the stent 105 downward through a slot in the outer tube 318. The pusher 320 can be in a fully retracted configuration via the knob 311, allowing the inner cavity of the outer tube 318 to freely receive the cut stent 105 through the 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, rather than being specifically loaded into the inner cavity of the outer tube 318. For example, loading into the inner cavity of the outer tube 318 can occur after additional steps such as advancing the support 105 toward the inner cavity of the outer tube 318 after cutting. Various sheath loading configurations are considered 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 trephine of the material sheet 101 can position the support 105 in a position that allows it to be deployed into the eye (i.e., axially aligned with the inner cavity of the shaft) without requiring manual tissue transfer of tiny cut material sheets.

Figure 5 shows another embodiment of the conveyor 110. This embodiment has a removable trephine box 205 near the end of the conveyor 110. Once the support has been formed within the cavity of the shaft 310, this embodiment reduces or minimizes the travel distance of the support 105.

Similar to the previous embodiments shown in Figures 3 and 4, the conveying 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 actuators 315 may include first and second sliders configured to move the outer sheath and pusher of the shaft 310, respectively. It should be understood that the device 110 does not need to combine 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 support 105, for example by causing movement of both the outer sheath and the pusher based on, for example, the degree of actuation of the slider.

The trephine box 205 may include a base 324 and a cover 314 movably attached to the base 324. The cover 314 and the base 324 are coupled together via a hinge 317, allowing the cover 314 to pivot about the hinge 317. As in previous embodiments, the cover 314 can be lifted to pivot into an open configuration, exposing a recess 321 in the base 324 within which the sheet material can be positioned and held in place. When the cover 314 rotates back to a closed configuration, the sheet material 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 can be simply detached, exposing the upper surface of the base 324, allowing the shaft 310 and the sheet material 101 to be properly positioned relative to the trephine box 205. The cover 314 can be configured to additionally apply a certain amount of tension to the material sheet 101, for example, by stretching it outward from the center of the material sheet 101 to improve the cutting.

Figure 6A shows a conveying device 110 having a trephine box 205 coupled to a distal region of a handle 305 in a closed configuration, in which the upper surface of a base 324 and the lower surface of a cover 314 of the trephine box 205 abut against each other. Figure 6B is a cross-sectional view of the device 110 in Figure 6A, showing a shaft 310 extending through the handle 305.

The trephine box 205 can be provided pre-loaded with a sheet of material positioned within a recess. For example, the sheet of material can be compressed and/or tensioned within the base 324 and the cover 314. The cutting member 312 can then be actuated to punch the support 105 out of the sheet of material, for example, by pressing down the button 313 to push the cutting member 312 through the sheet of material held within the trephine box 205. The delivery device 110 and the trephine box 205 can then engage with each other. For example, the shaft 310 can be inserted through a proximal port on the trephine box 205 to preload the cut support 105 into the outer tube 318 for delivery into the eye. The cut support 105 can be held securely within the trephine box 205. In a further embodiment, the support can be loaded from above, from the front, or from the rear of the shaft into a cut opening in the shaft.

It should be understood that the user does not need to cut the material sheet into a scaffold during implantation into the subject. The material sheet can be cut into a scaffold well before implantation, for example, in a tissue bank or tissue engineering laboratory. The scaffold can be provided as a pre-cut, pre-loaded scaffold in a cassette configured to be coupled to a delivery device. For example, a trephine cassette 205 can be provided to the user pre-loaded with a pre-cut scaffold 105 from a bio-derived material sheet. The cassette 205 holding the scaffold 105 can be coupled to the delivery device at implantation. Once coupled, the user can load the scaffold 105 into the shaft 310 of the delivery device, as described elsewhere herein. In a further embodiment, the scaffold 105 can be provided to the user pre-loaded within the cavity of the shaft 310. Material sheets can be provided in a cassette or within the cavity of the shaft 310, immersed in a suitable tissue preservative medium, as is known in the art.

In one embodiment, a user can manually load a sheet of material 101 through opposing cut-out windows 326 in an outer tube 318 extending through the shaft 310 of the conveying device 110 (see FIG. 7). The cut-out windows 326 in the outer tube 318 can extend through opposing sidewalls, allowing the sheet of material 101 to be inserted through a first cut-out window 326, across the inner cavity 328 of the outer tube 318, and through a second cut-out window 326 on the opposite side of the inner cavity 328. The cut-outs 326 are sized sufficiently to load the sheet of material 101 through them, as shown in FIG. 7. The sheet of material 101 can have a dimension wider than the outer diameter of the outer tube 318, such that each side of the sheet 101 extends beyond the sidewall of the outer tube 318. Each cut-out window 326 in the outer tube 318 can have a length along the longitudinal axis A of the shaft 310, which is at least as long as the sheet of material 101. The cut-out window 326 in the outer tube 318 can have a depth at least as thick as the material sheet 101. Figure 8A is a top view of the cut-out window 326 of the shaft 310. Figure 8B is a cross-sectional view of Figure 8A taken along line B-B. The cut-out window 326, created by removing the sidewall on either side of the outer tube 318, forms a narrow web 330 on the upper and lower surfaces of the tube 318.

Figures 9A-9B show another embodiment of the trephine box 205 having a cap 314 and a base 324. Figure 9A shows the base 324 with the cap 314 mounted. Figure 9B is a cross-sectional view of the box 205 showing a tissue sheet 101 sandwiched between the base 324 and the cap 314. Figure 9C shows the base 324 of the trephine box 205 containing a sheet 101 of material 101. A tube 318 is located outside a window 326 and within a recess 321 of the base 324. The recess 321 may be positioned between a proximal slot 332 and a distal slot 334. The proximal slot 332 is sized to receive at least a portion of the outer tube 318 located proximal to the incision window 326, and the distal slot 334 is sized to receive a portion of the outer tube 318 located distal to the incision window 326. The recess 321 can have any of a variety of shapes, but it can be of a generally sized design to receive the material sheet 101 loaded in the cut 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 in the proximal and distal slots 332, 334 and the tissue sheet 101 is located in the recess 321.

Still relating to Figures 9A-9C, the cover 314 may have an upper surface forming the outer surface of the box 205. The cover 314 may also include a lower surface configured to engage with the upper surface of the box base 324. The upper surface may include a recess 336, within which is the entrance to an orifice 338 extending 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 the entrance to an orifice 340 extending through at least a certain thickness of the base 324. The orifice 340 of the base 324 may, but does not necessarily, extend through the entire thickness of the base 324. When the cover 314 abuts the base 324, the orifices 338 and 340 align, thereby forming a continuous channel. The size and shape of the continuous channel are designed to receive a cutting member 312, which will be described in more detail below. The cutting member 312 can be translated 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.

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

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

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 show the handle 343 having a disc shape configured to be received within a correspondingly formed recess 336 in the upper surface of the cover 314. Any of various shapes are considered here.

The blade housing 342 may include a central channel 346 in which the 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 gap size is selected according to the desired width of the support 105 to be achieved when cutting the tissue slice 101 with the blades 344.

The cutting member 312 can be received within a recess 336 in the cover 314, such 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 Figure 10A). Therefore, the size and shape of the hole 338 in 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 size and shape of the handle 343 can be designed to be received within the recess 336 in the cover when the cutting member 312 is fully inserted into the housing 205.

The tissue sheet, held within the slit region of the axis, is cut in two locations, producing narrow strips of material (i.e., support 105) from the material sheet 101. As the cutting member 312 is further pushed through the hole 338 in the cap 314, the blade 344 is pushed against the material sheet 101 compressed between the cap 314 and the base 324 (see FIG. 10B). As the cutter is further pushed through the hole 338 in the cap 314 and into the hole 340 in the base 324, the blade 344 cuts through the tissue sheet 101 located within the recess 321 (see FIG. 10C). When the blade 344 extends downward through the hole 340 in the base 324 and completely cuts through the sheet 101, the blade 344 makes two cuts in the material sheet 101, forming the support 105. As the cutting member moves toward the cutting configuration, the movement of the cutter toward the cutting configuration cuts the material sheet into a support, and once the support is cut, it is axially aligned with the inner cavity 328 of the outer tube 318. The formed support 105 is thus already loaded relative to or within the inner cavity 328 of the outer tube 318, so no loading step is required.

The blade 344 is inserted through a continuous channel formed by holes 338, 340 in the cover 314 and the base 324. The housing 342 may be disposed within the hole 338 and/or the handle 343 may be disposed within the recess 336 of the cover 314 to prevent any further downward movement of the blade 344. The formed support 105 is held tightly within the inner cavity 328 of the outer tube 318. As described above, the outer tube 318 of the conveying device shaft 310 may include a pair of cut windows 326 on opposite sidewalls, forming narrow webs 330 on the upper and lower surfaces of the tube 318. As best shown in Figures 11A-11E, when the cutting member 312 is inserted into the housing 205, each blade 344 is received within the corresponding cut 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 designed to accommodate and receive the web 330 as the blades 344 slide past the shaft 318 positioned within the housing 205. Once cut, the support 105 is contained within the inner cavity 328 of the outer tube 318 at the location of the cut window 326, where one of the blades 344 surrounds the support 105 on a first side, and the second of the blades 344 surrounds the support 105 on a second side. The housing forms a path for the support 105 to be deployed from the inner cavity 328 to the distal end of the shaft 310, which will be described in more detail below.

Still relating to Figures 11A-11E, blade 344 may include a single bevel angled to deliver a cut, similar to scissors. Preferably, blade 344 does not cut tissue. Blade 344 is positioned relative to casket 205 such that a complete cut through blade 101 occurs as cutting member 312 travels fully through casket 205.

When the cutting member 312 is fully translated into the cover 314 (i.e., the cutting member 312 is placed into the cutting configuration), the blade housing 342 is confined within the hole 338 in the cover 314. Therefore, 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. In some embodiments, and preferably as shown in FIG10B, the distal outlet of the hole 338 at the lower surface of the cover 314 may have a smaller size than the inlet of the hole 338. Where the inlet size of the hole 338 is designed to receive the blade housing 342, the outlet size of the hole 338 may be designed to receive only the blade 344 and not the blade housing 342. This arrangement prevents the cutting member 312 from being over-inserted relative to the housing 205 because the lower region of the hole 338 acts as a stop for the blade housing 342.

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 prevents accidental damage to the blades 344 or the user when the cutting member 312 is not engaged with the housing 205. For example, the safety sheath may enclose the blades 344 completely except for the lower end of the cutting member 312. The cover 314 and base 324 of the housing 205 may include additional channels aligned, sized, and shaped to receive the safety sheath surrounding the blades 344 when the cutting member 312 is inserted into the housing 205.

Figure 11E shows a cross-sectional view of the cut-out window 326 of the outer tube 318, with the blade 344 located on either side of the upper web 330 and the lower web 330. As described above, the shaft 310 of the conveying device 110 may include a pusher 320 located within the inner cavity 328 of the outer tube 318. At least a portion of the pusher 320 may have a cross-sectional shape configured to slide over the blade 344 located within the cut-out window 326 of the tube 318. The cross-sectional shape of at least a portion of the pusher 320 may include a flat side configured to align with the cut-out window 326 as the pusher 320 extends relative to the outer tube 318 during the deployment of the support 105 from the inner cavity 328. The flat side of the pusher 320 (as opposed to a convex side) may define a width designed to slide between the two blades 344 located within the cut-out window 326. Similar to the support, at least a portion of the size of the pusher 320 can be designed to completely fill at least a portion of the inner cavity 328 of the outer tube 318. The outer tube 318 can be a thiocyanate tube, not larger than approximately 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 implementations, the outer tube 318 is a thiocyanate tube with an inner diameter less than about 0.036” and as small as about 0.009”. The size of the outer tube 318 can be selected based on the desired size of the stent to be implanted, as discussed in more detail above.

With the shaft 310 of the delivery device 110 mounted in the housing 205 and the blade 344 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 material sheet 101, in a preparatory 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 blade 344 on either side of the incision window 326 and the web 330 on the upper and lower sides prevents the stent 105 from buckling within the lumen 328 during this preparatory step. The catheter size held therein by the stent 105 matches the external dimensions of the implanted stent, thereby preventing buckling and wrinkling when the stent 105 is pushed into the preparatory position.

Once the support 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 housing 205 and the cover 314 can be opened relative to the base 324, allowing the shaft 310 of the delivery device 110 to be removed from the housing 205. In other embodiments, the cutting member 312 can be withdrawn from the base 324 but remains engaged with the housing 205 to allow the shaft 310 of the delivery device 110 to be removed from the housing 205. The shaft 310 can be withdrawn from the housing 205 regardless of whether the cover 314 is in an open or closed configuration. Once the delivery device 110 and the housing 205 are disengaged from each other, the delivery device 110 is ready for inserting the support 105 into the eye, as will be described in more detail below.

As described above, movement of the components of the conveying device 110 can be achieved using one or more actuators 315 of the handle 305. Figure 6B is a cross-sectional view of an embodiment of the conveying device 110, with its distal shaft 310 engaging with the trephine box 205. The shaft 310 may include a pusher 320 and an outer tube 318. The pusher 320 may be coupled to a first actuator 315 and the outer tube 318 may be coupled to a second actuator 315. Each of the first and second actuators 315 may be a slider configured to advance and retract their respective components. The first actuator 315 may be retracted proximally such that during cutting of the sheet of material 101 compressed and/or tensioned within the box 205, the pusher 320 is in its closest position to the outer tube 318. Once the material sheet 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 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 the tissue of the eye until approaching the target location. Once the delivery device is in place to deploy the stent 105 in the eye, the first actuator 315 coupled to the pusher 320 can be held in that distal position and the second actuator 315 retracted 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 (as shown in Figure 12B). It should be understood 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 understood that the advancement of the pusher 320 and the retraction of the outer tube 318 can be controlled by dual actuators 315, as described above, or by a single actuator 315, which, depending on the degree of actuation, is capable of moving both the pusher and the outer sheath. Furthermore, the shaft 310 of the delivery device 110 can be used during surgery to inject viscoelastic material using the pusher 320 as a plunger.

Figures 13A-13B and 18A-18B illustrate relevant embodiments of the delivery device 1110, which has an integrated trephine to form a system for preparing the implant and performing endoscopic insertion of the implant into the eye. As described elsewhere herein, the delivery device 1110 can be inserted into the eye and used to implant the stent 105 into the implantation site via an endoscopic delivery path. 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 Figure 14A). An axially movable cutting tube 1312 may 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 while the delivery device is described herein as suitable for performing endoscopic insertion of the implant, other implantation methods are also considered. For example, the delivery device can be used to perform a transscleral method for delivering the implant.

Still relating to Figure 14A, the conveying device 1110 may include an access door 1314 coupled to an area of the handle 1305, for example, via 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 the open configuration, a recess 1321 is exposed. A sheet of material 101 may be loaded within the recess 1321 for cutting into a support 105 prior to conveying. A pusher 1320, positioned within the cavity 1378 of the cutting tube 1312, retracts proximally relative to the recess 1321, allowing the sheet of material 101 to be positioned within the recess 1321. Figure 14B shows the access door 1314 rotated to the closed configuration, thereby capturing the sheet of material 101 within the recess 1321. In some embodiments, the access door 1314 may be formed of a transparent or translucent material, such that the material sheet 101 positioned within the recess 1321 can be seen 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 open the door 1314 again. In some embodiments, the latches of the access door 1314 may include an interference fit feature or a magnet, or other elements.

The recess may be within a portion of the instrument, such as within the handle as described above. The recess may also be within a case removably coupled to the instrument. As shown herein, the case may be coupled to the distal portion of the instrument and removed before deployment into the eye. The case may also be coupled to the proximal portion of the instrument and may be removed or not removed before deployment.

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

In some embodiments, at least a portion of the recess 1321 may have a depth less than the thickness of the material sheet 101 held within the recess 1321, for example, this portion may be aligned with the centerline of the implanted catheter. When the door 1314 is closed, the material sheet 101 is slightly compressed.

At least a portion of the material sheet 101 can be placed under tension before cutting. When the material sheet 101 is placed under slight tension before cutting, the cutting achieved by the cutting tube 1312 is improved. Tensioning this portion of the sheet may include a first and second portion of the compressing sheet and a central portion of the tensioning sheet located between the first and second portions. When the sheet is cut with the cutting tube 1312, the central portion of the sheet becomes an implant.

This portion of the tensioning sheet may include an actuating actuator to tension that portion of the sheet. The actuating actuator may include a rotary actuator to tension that portion of the sheet. For example, a cover may include an actuator, and actuation of the actuator may tension at least a portion of the sheet. However, tensioning does not need to be a separate actuation. As discussed elsewhere herein, closing the access door 1314 may provide fixation and a certain amount of tension to the sheet. Figures 15A-15C are schematic cross-sectional views of the handle 1305 showing the access door 1314 and the sheet 101 positioned within the recess 1321. The door 1314 may include features configured to apply a small amount of tension or stretching force to the sheet 101 to improve cutting. The door 1314 may be coupled to a tensioner 1350 having a pair of flexible tensioner legs 1352. The tensioner legs 1352 extend into the recess 1312 until each foot 1354 at the end of the leg 1352 contacts the sheet 101 (see Figure 15B). One foot 1354 may contact a first portion of the material sheet 101 on a first side of the centerline, and the opposite foot 1354 may contact a second portion of the material sheet 101 on an opposite second side of the centerline. The stretcher 1350 can be actuated from a first position in which the stretcher 1350 is raised relative to the recess 1321. When the stretcher 1350 is pushed downwards, the stretcher leg bends and the feet 1354 are pushed further outwards away from the centerline and away from each other (see arrows in Figure 15C). The distance between the feet 1354 is sufficient to allow the cutting tube to slide axially across the recess 1321 between the feet 1354 to cut the material sheet 101. The lower surface of the feet 1354 may have surface features 1355, such as ridges, bumps, or other textures optimizing the interface between the feet 1354 and the material sheet 101. Surface features 1355 allow the feet 1354 to stretch the material sheet 101 outwards when the feet 1355 are pushed outwards.

The tensioner 1350 can have any of a variety of configurations. The tensioner 1350 can be a button as shown in Figures 13A-13B and 15A-15C. The tensioner 1350 can be a dial as shown in Figures 18A-18B, 19A-19B, 20A-20C, 21, and 22. Any of a variety of other actuators 101 configured to apply tension on the sheet can be considered. In embodiments where the tensioner 1350 is a button, the gate 1314 can be additionally combined with a tension release button 1357 (see Figure 13A) to release the applied tension if desired.

Regardless of the configuration, the tensioner 1350 may have an upper region 1360 and a lower region 1362 (see Figure 20A). The upper region 1360 is configured to be gripped and actuated (i.e., pushed or rotated). The lower region 1362 of the tensioner 1350 may engage with the access door 1314. Figure 21 shows an embodiment of the tensioner 1350 having a dial with threads 1367 on the lower region 1362 of the tensioner 1350, which engages with a corresponding thread 1365 of a hole 1364 in the upper surface of the door 1314. Rotation of the tensioner 1350 relative to the hole 1364 pulls the tensioner 1350 further down into the hole 1364 and pushes the foot 1354 further into the recess 1312.

As discussed elsewhere in this document, 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 door 1314 can achieve both securing and tensioning of the sheet material without requiring a separate actuator to provide tension on the sheet material after compression. Thus, door 1314 can achieve a preset tension on the sheet material when closed without requiring separate activation of tensioner 1350 relative to the material upwards or downwards.

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

The cutting member may include a cutting member cavity, a distal opening, and a pair of opposing cutting edges. Cutting may include advancing the cutting member to cut a piece of material and capture the implant within the cutting member cavity. The pair of opposing cutting edges may cut the piece in two locations to separate the implant from the remainder of the piece of material. The distal portion of the cutting member may be beveled. As the cutting member completes cutting the piece to form the implant, the longitudinal axis of the implant may remain aligned with the longitudinal axis of the cutting member cavity.

The cutting tube 1312 can be a double-beveled thallium tube forming two guide points 1372 (see Figures 23A-23D). When the cutting tube 1312 is advanced into the cutting configuration and cuts through the material block 101, the two guide points 1372 can be located above and below the material block 101, respectively. The lower guide point 1372 can be received within a shallow central channel 1372 of an inverted V-shape 1371, and the upper guide point 1372 slides on the material sheet 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, such that the cutting tube 1312 cuts the material sheet 101 in two locations. Therefore, the inner diameter or distance between the inner edges 1374 of the cutting tube 1312 determines the width of the cut support 105.

Once cut, the stent 105 is contained within the lumen 1378 of the cutting tube 1312, thus forming a shell of the stent 105. The stent 105 may have dimensions that substantially fill the lumen 1378 of the cutting tube 1312. The cutting tube 1312 is positioned by axial movement in a direction toward the distal side of the cutting configuration such that its walls bridge the recess 1321 and form part of the implantation catheter 1319. The lumen 1378 of the cutting tube 1312 may be coaxial (e.g., connected or unconnected) with the lumen of the elongated shaft 1310 through which the stent 105 will be delivered to the eye. For example, as shown in FIG17B, the cut stent 105 may be advanced out of the cutting tube 1312 along the implantation catheter 1319 toward the distal end of the delivery shaft 1310. Therefore, the cutting tube 1312 moves axially along the axis of the implantation catheter 1319 while simultaneously cutting the stent from the material sheet 101 and axially aligning the cut stent with or relative to the delivery shaft lumen, so that the stent 105 can be deployed in the eye without any tissue transfer steps.

An inner elongated member or pusher 1320 is movable relative to the inner cavity of the delivery shaft. The support 105 can be pushed distally from the cutting tube 1312 via the pusher 1320. As described above, the elongated shaft 1310 of the delivery device 1110 may include an outer tube 1318 and an inner pusher 1320 located within the inner cavity of the outer tube 1318. The pusher 1320 is sized and shaped to travel distally through the inner cavity 1378 of the cutting tube 1312 to push the support 105 toward the distal end of the outer tube 1318 (see FIG. 17B). In some embodiments, the outer tube 1318 is fixed relative to the handle 1305 and the inner pusher 1320 is movable relative to the outer tube 1318 to deploy the support 105 from the outer tube 1318. In other embodiments, the outer tube 1318 and the pusher 1320 are movable relative to the handle 1305 and relative to each other. The distal end of the actuator 1320 can be configured to push the stent 105 non-invasively in the distal direction.

In a further embodiment, the elongated delivery shaft 1310 may include a fixed outer tube 1318 and a guide tube 1380, the guide tube 1380 being positioned and movable through the inner cavity 1328 of the outer tube 1318 (see Figures 18A-18B). A pusher 1320 is also movable through the inner cavity 1382 of the guide tube 1380. The distal region of the elongated tubular member for delivering the implant into the eye may be angled, curved, and/or flexible. In some embodiments, the guide tube 1380 may have a curved shape in its distal region and/or the guide tube 1380 may be flexible to conform to a curved shape. The curved shape of the distal region of the guide tube 1380 may conform to the shape of the desired implantation site, such as the curvature of the eye near the anterior corner. The outer tube 1318 may be a rigid tube and the guide tube 1380 may be flexible. The actuator 1320 may be a shaped nitinol that, when retracted proximally, takes on the shape of a rigid outer tube 1318 and when extended distally beyond the distal opening of the outer tube 1318, allows relaxation back to its shaped configuration (i.e., having a bend or buckling away from the longitudinal axis of the outer tube 1318). When the actuator 1320 extends beyond the outer tube 1318, the guide tube 1380 may have sufficient flexibility to take on the shape of the actuator 1320. Therefore, the guide tube 1380 may be more flexible than the actuator 1320, and the actuator 1320 may be more flexible than the outer tube 1318. In some embodiments, the guide tube 1380 may be formed of silicone, thermoplastic elastomer, polyethylene, polypropylene, or combinations thereof. The guide tube 1380 may have a degree of rigidity, but not so rigid that it cannot retract through the actuator 1320 during deployment.

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 into the lumen 1382 of the guide tube 1380. Figure 24A shows the guide tube 1380 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 by the pusher 1320 through the lumen 1382 until the stent 105 is located in the distal region of the guide tube 1380 (Figure 24B). During this deployment phase, the actuator 1320 has been advanced a distance beyond the distal end of the rigid outer tube 1318, allowing the actuator 1320 to relax back to its bent or flexed shape. A guide tube 1380, which may be more flexible than the actuator 1320, takes on the shape of the actuator 1320. The cut stent 105, positioned near the distal end of the guide tube 1380, is ready to be implanted into the eye. The guide tube 1380 can retract while the actuator 1320 remains stationary to effectively push the stent 105 out of the lumen of the guide tube 1380 (see Figure 24C).

Advancing the implant from the proximal portion of the device 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 portion of the device 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 remains at least partially within the lumen of the distal portion of the device. The stent 105 may be deployed from the device as the guide tube 1380 retracts from the implant, while maintaining the implant's position relative to adjacent ocular tissue. The method of implantation and delivery of the stent 105 is described in more detail below.

Movement of the cutting and deployment components (e.g., one or more of the cutting tube 1312, pusher 1320, guide tube 1380, and outer tube 1318, if present) can be achieved 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 conveying device 1110 may be located on a first region of the handle 1305, and one or more actuators 1315 for a second function of the conveying device 1110 may be located on a second region of the handle 1305. A first plurality of actuators 1315 may be located on the first region of the handle 1305 to prepare the material sheet 101 into a support, and a second plurality of actuators 1315 may be located on the second region of the handle 1305 to deploy the support 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 support 105 in a pre-position for deployment from the device 1110. The bottom region of the handle 1305 may include a fourth actuator 1315 for deploying the support 105 in the eye.

Figure 13A shows a top view of an embodiment of the conveying device 1110, and Figure 13B shows a bottom view of the device 1110. The top region of the handle 1305 may include a first actuator 1315, which is a tensioner 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 the pusher 1320 to push the support 105 from the outer tube 1318.

Figure 18A shows a top view of an embodiment of the conveying device 1110, and Figure 18B shows a bottom view of the device 1110. 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-loaded retraction button for retracting the guide tube 1380 to release the support 105 from the shaft 1310.

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

In one embodiment, one or more actuators 1315 of one or more components configured as an axial movement device may include rollers 1385 (see FIG. 25). Rollers 1385 may be connected to pinions 1387, which engage with corresponding racks 1389. Rotation of the pinions 1387 can cause the racks 1389 to move axially and advance or retract any axially movable component, such as pusher 1320 or cutter tube 1312. FIG. 25 shows the rack 1389 attached to pusher 1320. Rollers 1385 can provide more incremental, precise movement of components. Roller propulsion mechanisms are described in US10,154,924, and are incorporated herein by reference.

In another embodiment, one or more actuators 1315 of one or more components configured as an axial movement device may include a spring-loaded button 1390. The guide tube 1380 can be pushed in a distal direction in an extended state relative to the handle 1305, compressing the spring 1392 (see FIG. 26). The button 1390 can be held in a forward-locked position by a latch 1394, such that the spring 1392 remains compressed as the support 105 advances to a 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 actuator 1320 can be used to release the implant 105 into the eye. A spring-loaded retraction mechanism is described in US 9,241,832, and is incorporated herein by reference.

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

Advancing the cutting tube 1312 cuts the stent 105 from the material sheet, causing the stent 105 to be positioned within the lumen of the cutting tube 1312. The inner diameter of the cutting tube 1312 may be substantially the same as the inner diameter of the outer guide tube 1380. The pusher 1320 may be pushed distally through the lumen of the cutting tube 1312, pushing the cut stent 105 within that lumen into the lumen of the guide tube 1380. However, because the internal dimensions of the cutting tube 1312 and the guide tube 1380 may be substantially the same, the cutting tube 1312 may be pushed posteriorly by the guide tube 1380 when the guide tube 1380 is pushed proximally by a spring. The stent 105 may be substantially contained within the implantation catheter and is advanced line-to-line within the device when it is pushed distally. Once the stent 105 is cut from the material sheet, 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 catheters in between, thus avoiding transfer between necessary "gaps" or "edges" within the implantation catheter during the entire delivery process of the stent within the implantation catheter. The implantation catheter provides a smooth path for deploying the stent 105 via instruments.

Tissue trephination and tissue loading using a delivery device can be performed simultaneously or sequentially. In a preferred embodiment, cutting and injection are integrated. This allows tissue cutting/trephination to be performed within/along the implantation path. The size of the tissue strip makes it difficult to manipulate. Therefore, by integrating cutting and implantation, no additional manipulation is required. 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 trephinate tissue to form a scaffold, which is then injected/implanted into the eye, enabling seamless and non-invasive loading of fine, micro-sized biological scaffold tissue without transport manipulation.

The tissue can be, for example, the cornea, sclera, or other cartilage tissue. A segment 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 before transferring it to an intraocular delivery device. In the case of using a single integrated trephine/injection device, this device is used for trephineing the tissue and for injecting and implanting the tissue into the eye.

In another implementation, simultaneous or sequential tissue trephination and tissue insertion into the eye are performed. Tissue segments are cut and loaded into a tissue delivery path. This is performed using a single device configured to trephinate tissue and to load the trephinated tissue into an intraocular delivery applicator for tissue application to the eye.

The application device can also be used as a delivery device and loading platform device or conduit. In such implantation, the device is configured to contain or otherwise accommodate tissue prior to implantation. The device allows for longitudinal or other directional movement of the tissue for implantation into the eye. The device can be configured to perform trephination and application loading simultaneously or sequentially, such that after the trephination step is completed, the trephinated or cut tissue is loaded into the delivery conduit of the application device. The trephination device can be coupled to the intraocular delivery device via coupling or other attachment mechanisms, which facilitates the transfer of tissue into the delivery device.

The stent can be harvested from the patient during surgery using a trephine device. The stent can also be formed from sheets of material obtained from a donor or other tissue-engineered sources. The sheets can be pre-cut into a stent shape and pre-loaded into the delivery area. The sheets can be cut using a trephine device during implantation.

In one embodiment, the material sheet 101 can be manually loaded through a cut-out window 326 in the outer tube 318, wherein the pusher 320 in the inner cavity 328 of the outer tube 318 is fully retracted in the proximal position. Once the material sheet 101 is loaded into the conveyor 110, the shaft 310 and the material sheet 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 conveyor 110 is positioned within slots 332, 334 such that the material sheet 101 is positioned between them within the recess 321.

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

In one embodiment, a material sheet 101 may be loaded into a recess 1321 of the delivery device 1110. An access door 1314 may be opened and the material sheet 101 placed in the recess 1321. The door 1314 may be closed, thereby capturing and at least partially compressing the material sheet 101 within the recess 1321. A tensioner 1350 may be actuated to apply tension to the material sheet 101 prior to cutting with the cutting tube 1312. The cutting tube 1312 may be actuated to slide distally, thereby cutting the material sheet 101 into a support 105. The pusher 1320 may then be pushed distally to prepare the shaft 1310 by positioning the cut support 105 in the distal region of the lumen 1382 of the guide tube 1380. Once pushed distally towards the rigid outer tube 1318, the pusher 1320 may relax into a curved shape, thereby causing the guide tube 1380 to also take on this curved shape. The delivery device 110 is now ready for the patient. As described above, the guide tube 1380 may be flexible and/or have a curved shape in its distal region, which is configured to conform to the shape of the desired implantation site, such as the curvature of the eye near the anterior corner.

Typically, the stent 105, located within the shaft of the delivery device, can be implanted through a patent corneal or scleral incision formed using the delivery device or a device separate from the delivery device. An observation lens, such as a gonioscope, can be positioned near the cornea. The observation lens allows visualization of internal areas of the eye, such as scleral spurs and the scleral junction, from a position anterior to the eye. The observation lens may 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 aid visualization. Ultrasound guidance can also be used with a high-resolution biological microscope, OCT, etc. Alternatively, a small endoscope can be inserted through another limbal incision in the eye to image the eye during implantation.

The distal end of the axis of the retainer 105 can penetrate the cornea (or sclera) to access the anterior chamber. In this regard, a single incision can be made in the eye, for example, within the limbus. In one embodiment, this incision is very close to the limbus, for example, at the level of the limbus or within 2 mm of the limbus in a clear cornea. The incision can be formed using the axis, or a separate cutting device can be used. For example, a blade-tip device or a diamond blade can be initially used to enter the cornea. A second device with a scraper tip can then be advanced above the blade tip, wherein the plane of the scraper is positioned to coincide with the anatomical plane.

The corneal incision can be large enough to allow the axis to pass through. In one embodiment, the incision size is approximately 1 mm. In another embodiment, the incision size is no greater than approximately 2.85 mm. In yet another embodiment, the incision is no greater than approximately 2.85 mm and greater than approximately 1.5 mm. It has been observed that incisions up to 2.85 mm are self-sealing incisions.

After insertion through the incision, the shaft can be advanced into the anterior chamber along a path that allows the stent 105 to be delivered from the anterior chamber to the target location (e.g., the supraciliary space and/or suprachoroidal space). Approaching by positioning the shaft allows it to be further advanced into the eye, such that the distal end of the shaft penetrates tissue at the angle to the eye, such as the iris root or ciliary body region, or the iris root portion of the ciliary body near its tissue boundary with the scleral osteophyte.

Scleral osteophytes are anatomical landmarks on the canthal wall of the eye. They are above the level of the iris but below the level of the trabecular meshwork. In some eyes, scleral osteophytes may be obscured by the lower band of the pigmented trabecular meshwork and located directly behind it. The axis can travel along a path toward the canthus and the scleral osteophyte, such that the axis passes near the scleral osteophyte on its way to the supraciliary space of the ciliary body, but does not necessarily penetrate it during delivery. Instead, the axis can move close to the scleral osteophyte and downward to dissect the tissue boundary between the sclera and ciliary body, with the anatomical entry point beginning below the scleral osteophyte immediately adjacent to the iris root or ciliary body root. In another embodiment, the delivery path of the implant intersects with the scleral osteophyte.

The axis can approach the corner of the eye from the same side of the anterior chamber as the deployment location, so that the axis does not have to be advanced through the iris. Alternatively, the axis can approach the corner of the eye from through the anterior chamber AC, so that the axis is advanced through the iris and/or the 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 cross the eye and does not intersect the central axis of the eye. In other words, when looking toward the eye along the optical axis, the corneal incision and the location of the stent 105 implanted at the corner of the eye can be in the same quadrant. Furthermore, the path of the stent 105 from the corneal incision to the corner of the eye should not cross the central line of the eye to avoid interfering with the pupil.

The axis can be continuously advanced into the eye, for example, about 6 mm. The anatomical plane of the axis can follow the curve of the inner scleral wall, so that the support 105 installed in the axis, for example after penetrating the iris root or the iris root portion of the ciliary body CB, can bluntly dissect the boundary between the tissue layers of the scleral osteophyte and the ciliary body CB, so that the distal region of the support 105 extends through the ciliary body space and is then further positioned between the tissue boundaries of the sclera and choroid that form the suprachoroidal space.

Once correctly positioned, the bracket 105 can be released. In some embodiments, the bracket 105 can be released by retracting the outer tube 318 of the shaft 310, while the pusher 320 prevents the bracket 105 from retracting along with the outer tube 318. In other embodiments, the bracket 105 can be released by retracting the guide tube 1380 while the pusher 1320 remains fixed, as described elsewhere herein.

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

As mentioned above, the materials used to form the scaffold can be impregnated with one or more therapeutic agents for additional treatment of the eye disease process.

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

The device of the present invention can deliver drugs of the following classes: antiproliferative agents, antifibrotic agents, anesthetics, analgesics, cell transport/mobility inhibitors, such as colchicine, vincristine, cytochalasin B and related compounds; antiglaucoma drugs including β-receptor blockers such as timolol, betalol, atenolol and prostaglandin analogs such as bimatoprost, travoprost, latanoprost, etc.; carbonic anhydrase inhibitors, such as acetazolamide, metronidazole, dichlorobenazine, acetazolamide; and neuroprotective agents, such as nimodipine and related compounds. Additional examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, brevicin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; antibacterial agents such as sulfonamides, sulfaacetamide, sulfadimazole, and sulfisoxazole; antifungal agents such as fluconazole, furacilin, amphotericin B, ketoconazole, and related compounds; antiviral agents such as trifluorothymidine, acyclovir, ganciclovir, DDI, AZT, phosphonoformic acid, vidarabine, trifluorouridine, idoxuridine, ribavirin, protease inhibitors, and anticytomegalovirus agents; antiallergic agents such as dexamethasone; chlorpheniramine, pyrazinamide, etc. Lamine and pyridine; anti-inflammatory agents, such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, flumethasone, betamethasone, and triamcinolone; decongestants, such as phenylephrine, naphazoline, and tetrahydrazine; miotics and anticholinesterases, such as pilocarpine, carbachol, diisopropyl fluorophosphate, iodophosphine, and diergotamine bromide; mydriatics, such as atropine sulfate, cyclopentolpine, homatropine, scopolamine, tocatropin, and eucatropin; sympathomimetic drugs, such as adrenaline and vasoconstrictors and vasodilators; ranibizumab, bevacizumab, and triamcinolone.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can also be delivered, such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, ibuprofen from Bayer AG, Leverkusen, Germany; indomethacin from Wyeth, Collegeville, Pa., Leverkusen, Germany; mefenamic acid), COX-2 inhibitors (COX-1 inhibitors from Pharmacia Corp., Peapack, NJ), including prodrug 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, fibrinolytic agents, and anticoagulation activating enzymes can also be delivered.

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

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

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

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

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

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

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

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

Claims (6)

1. A stent having a first end and a second opposing end, the stent having no internal cavity, wherein the first end is configured to be located within the anterior chamber of the eye, and the second opposing end is configured to be located within the Schrem's canal of the eye to form a fluid communication path between the anterior chamber and the Schrem's canal. 2. The scaffold according to claim 1, wherein the scaffold comprises a bio-derived material. 3. The scaffold of claim 2, wherein the bio-derived material comprises tissue collected from a donor or from the eye. 4. The scaffold according to claim 2, wherein the bio-derived material is an autologous graft, an allogeneic graft, or a xenograft material. 5. The scaffold according to claim 1, wherein the scaffold is an engineered tissue. 6. The scaffold according to claim 5, wherein the engineered tissue is a 3D-printed material suitable for implantation.