Patent ID: 12257188

It should be appreciated that the drawings are for example only and are not meant to be to scale. It is to be understood that devices described herein may include features not necessarily depicted in each figure.

DETAILED DESCRIPTION

Disclosed are implants, systems, and methods for increasing aqueous outflow from the anterior chamber of an eye. As will be described in detail below, ab interno outflow stenting using biological, cell-based or tissue-based materials provides biocompatible aqueous outflow enhancement with improved tolerability and safety over conventional shunts. In an example implementation, a biologic tissue or biologically-derived material is harvested or generated in vitro and formed into an implant, also referred to herein as a stent, using a trephination device or cutting tool. In an implementation, the stent is an elongated body or strip of tissue that does not have an internal lumen. Lumen-based devices can be limited by the lumen acting as a tract for fibrotic occlusion. The stent formed from the tissue is then implanted into the eye via an ab interno delivery pathway to provide aqueous outflow from the anterior chamber. The stents described herein can be used as a phacoemulsification adjunct or stand-alone treatment to glaucoma as a micro-invasive glaucoma surgery (MIGS) treatment.

Use of the terms like stent, implant, shunt, bio-tissue, or tissue is not intended to be limiting to any one structure or material. The structure implanted can, but need not be a material that is absorbed substantially into the eye tissue after placement in the eye such that, once absorbed, a space may remain where the structure was previously located. The structure once implanted may also remain in place for an extended period and not substantially erode or absorb.

As will be described in more detail below, the stents described herein can be made from biologically-derived material that does not cause toxic or injurious effects once implanted in a patient.

The term “biologically-derived material” includes naturally-occurring biological materials and synthesized biological materials and combinations thereof that are suitable for implantation into the eye. Biologically-derived material includes a material that is a natural biostructure having a biological arrangement naturally found within a mammalian subject including organs or parts of organs formed of tissues, and tissues formed of materials grouped together according to structure and function. Biologically-derived material includes tissues such as corneal, scleral, or cartilaginous tissues. Tissues considered herein can include any of a variety of tissues including muscle, epithelial, connective, and nervous tissues. Biologically-derived material includes tissue harvested from a donor or the patient, organs, parts of organs, and tissues from a subject including a piece of tissue suitable for transplant including an autograft, allograft, and xenograft material. Biologically-derived material includes naturally-occurring biological material including any material naturally found in the body of a mammal. Biologically-derived material as used herein also includes material that is engineered to have a biological arrangement similar to a natural biostructure. For example, the material can be synthesized using in vitro techniques such as by seeding a three-dimensional scaffold or matrix with appropriate cells, engineered or 3D printing material to form a bio-construct suitable for implantation. Biologically-derived material as used herein also includes material that is cell-derived including stem cell(s)-derived material.

The biologically-derived material, sometimes referred to herein as bio-tissue or bio-material, that is used to form the stent can vary and can be, for example, corneal tissue, scleral tissue, cartilaginous tissue, collagenous tissue, or other firm biologic tissue. The bio-tissue can be of hydrophilic or hydrophobic nature. The bio-tissue can include or be impregnated with one or more therapeutic agents for additional treatment of an eye disease process.

Non-biologic material includes synthetic materials prepared through artificial synthesis, processing, or manufacture that may be biologically compatible, but that are not cell-based or tissue-based. For example, non-biologic material includes polymers, copolymers, polymer blends, and plastics. Non-biologic material includes inorganic polymers such as silicone rubber, polysiloxanes, polysilanes, and organic polymers such as polyethylene, polypropylene, polyvinyls, polyimide, etc.

Regardless the source or type of biologically-derived material, the material can be cut or trephined into an elongated shape suitable for stenting and implantation in the eye. This trephination process of the tissue can be performed before the surgical implantation process or during the surgical implantation process. The stent(s) implanted in the eye may have a structure and/or permeability that allows for aqueous outflow from the anterior chamber when positioned within a cyclodialysis cleft.

FIG.1is a cross-sectional view of a human eye showing the anterior chamber AC and posterior chamber PC of the eye. A stent105can be positioned inside the eye in an implanted location such that at least a first portion of the stent105is positioned in the anterior chamber AC and a second portion of the stent105is positioned within tissues such as within the supraciliary space and/or suprachoroidal space of the eye. The stent105is sized and shaped such that the stent105can be positioned in such a configuration. The stent105provides or otherwise serves as a passageway for the flow of aqueous humor away from the anterior chamber AC (e.g. to the supraciliary space and/or suprachoroidal space). InFIG.1, the stent105is represented schematically as an elongated body. It should be appreciated that the size and shape of the stent105can vary.

The stent105can be implanted ab interno, for example, through a clear corneal incision or a scleral incision. The stent can be implanted to create a communication between the anterior chamber AC and the supraciliary space, the anterior chamber AC and the suprachoroidal space, the anterior chamber AC and Schlemm's canal, or the anterior chamber AC and the sub-conjunctival space. In a preferred implementation, the stent105is implanted such that a distal end is positioned within a supraciliary position and the proximal end is positioned within the anterior chamber AC to provide a supraciliary cleft. The distal end of the stent105can be positioned between other anatomical parts of the eye.

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

The stent105described herein can be formed of any of a variety of biologically-derived materials having a permeability and/or structure that allows for aqueous filtration therethrough. The stent105can be formed of a biologically-derived material that is harvested, engineered, grown, or otherwise manufactured. The biologically-derived stent material can be obtained or harvested from a patient or from donors. The biologically-derived stent material can be harvested before or during surgery. The biologically-derived stent material can be synthetic bio-tissue created using in vitro techniques. The biologically-derived material can be stem cell generated or bioengineered. The tissue can be generated via in situ cellular or non-cellular growth. In an example implementation, the tissue can be 3D printed during manufacture.

The 3D printed tissue can be printed as a larger patch of material that is then cut at the time of surgery as described elsewhere herein. Alternatively, the 3D printed tissue can be printed to have the dimensions of the final implantable stent. In this implementation, the 3D printed material need not be trephined before implantation, but can be implanted directly. For example, the 3D printed stent can be printed directly into a cartridge that is configured to operatively couple with the delivery device described herein, which is in turn used to deploy the 3D printed stent into the eye. The 3D printed stent can be generated using the 3D printing process described inBiofabrication,2019; 11 (3).

In an example implementation, the stent105is made of a bio-tissue. The biologically-derived material can be corneal tissue and/or non-corneal tissue. The biologically-derived material may include corneal, scleral, collagenous or cartilaginous tissue. In an implementation, the biologically-derived stent material can be denuded corneal stromal tissue without epithelium and endothelium that is porous and has hydrophilic permeability to allow aqueous filtration. The biologically-derived material of the stent105can, but need not be incorporated into the eye's inherent anatomy after placement in the eye. The stent can cause the surrounding tissue to form a pathway that remains open for an extended period, even after absorption of the stent. The biologically-derived stent material may not significantly absorb or be incorporated into the eye's anatomy such that the stent105remains implanted for an extended period of time or indefinitely, as needed.

In other implementations, the stent105material may be manufactured of a complex carbohydrate or a collagen that is non-inflammatory. The stent105may also be formed of a biodegradable or bioabsorbable material including biodegradable polymers including hydroxyaliphatic carboxylic acids, either homo- or copolymers, such as polylactic acid, polyglycolic acid, polylactic glycolic acid; polysaccharides such as cellulose or cellulose derivatives such as ethyl cellulose, cross-linked or uncross-linked sodium carboxymethyl cellulose, sodium carboxymethylcellulose starch, cellulose ethers, cellulose esters such as cellulose acetate, cellulose acetate phthallate, hydroxypropylmethyl cellulose phthallate and calcium alginate, polypropylene, polybutyrates, polycarbonate, acrylate polymers such as polymethacrylates, polyanhydrides, polyvalerates, polycaprolactones such as poly-c-caprolactone, polydimethylsiloxane, polyamides, polyvinylpyrollidone, polyvinylalcohol phthallate, waxes such as paraffin wax and white beeswax, natural oils, shellac, zein, or a mixture.

As mentioned, the biologically-derived stent material can have a permeability or porosity that allows for aqueous filtration for sufficient control or regulation of intraocular pressure. Permeable bio-tissues described herein (e.g. sclera, cornea, collagen, etc.) are preferred stent materials, however, any bio-tissue, even if impermeable, is considered herein as a potential stent material to serve as a structural spacer that keeps the cyclodialysis open. Preferably, the material of the stent can create a gap that allows fluid to flow. The gap created can run longitudinally along each side of the stent. If the material of the stent is permeable, more fluid can pass through the cyclodialysis than if the stent material is impermeable and the fluid is required to pass along the outside of the stent. Thus, the material considered herein need not be porous in order to provide the desired function, however, the function can be enhanced by the porosity of the material.

Generally, the biologically-derived stent material has some firmness such that it can maintain outflow from the anterior chamber, however, is less stiff than conventional non-biologically-derived polyimide shunts used in the treatment of glaucoma (e.g. Cypass, Alcon). The stent material may have a sufficient structure to serve as a spacer to prop open a sustained supraciliary outflow. The stent material can maintain its structural height or thickness once implanted within the cyclodialysis such that fluid flow through or around the stent is provided. Biologically-derived stent material provides advantages in terms of biocompatibility, anatomic conformity, and aqueous permeability compared to conventional non-biological materials such as polyimide. Biologically-derived stent material can provide better conformability and compliance to the scleral wall and can be less likely to cause endothelial and scleral erosion/loss over time and with chronic eye rubbing and blinking.

In an implementation, the material used to form the stent is provided as an uncut patch of material configured to be manually loaded within the delivery device at the time of implantation. In other implementations, the biologically-derived material used to form the stent is provided as an uncut patch pre-loaded within the shaft of the delivery device and held within a trephination device205or cartridge. In still further implementations, the stent105comes already cut into the shape of the stent pre-loaded in the delivery device shaft310or within a cartridge configured to be loaded with the delivery device. The portion of the device carrying the biologically-derived stent material (whether pre-cut to a stent size or as the larger patch size) can be packaged in such a way that the material is stored in medium or other suitable preservative solution for the biologically-derived material. In some implementations, the entire device is packaged in a fluid bath or a portion of the device submerged in a separate container prior to attaching it to a trephination device or delivery device at the surgical site.

After the appropriate material has been obtained and prepped, a trephination device can be used to create an elongated stent of a predetermined dimension from the patch of material. As will be discussed in greater detail below, the trephination can be done at the time of surgery or prior to surgery. In certain implementations, the stent is formed by 3D printing and can be printed into a desired final dimension for the stent or can be printed as a patch of material that is then trephined at the time of or prior to surgery. The trephination achieved by the devices described herein results in very thin strips of material that can be implanted in the eye to provide regulation of aqueous outflow. The trephination achieved positions the cut implant within a conduit or lumen of the delivery device such that the cut implant may be subsequently delivered from the delivery device without needing to remove or transfer the cut implant from the cutting element into the delivery tube. The process of trephination can simultaneously or in subsequent actuations load the cut implant into a delivery conduit for implantation in the eye.

The term “patch of material” as used herein refers to a piece of biologically-derived material having a size along at least one dimension that is greater than a size of the stent cut from the patch of material and implanted in the subject. In some implementations, the patch of material can have a generally square shape and the stent trephined from the patch of material can have a generally rectangular shape. For example, the patch of material can be about 7 mm wide×7 mm long×0.55 mm thick and the stent trephined from the patch of material can be 0.3-0.6 mm wide×7 mm long×0.55 mm thick. The dimensions of the patch of material and the trephined stent can vary. The patch of material and the trephined stent can each have the same length and the same thickness, but differ from one another in width. The patch of material and the stent trephined from the patch of material can also have different lengths and thicknesses. For example, the patch of material can have a first thickness and the stent trephined from the patch of material have the same thickness, but when implanted can be folded or rolled into a different thickness from the patch of material.

The stent trephined from the patch of material can have a width, a length, and a thickness. In an implementation, the width of the stent trephined from the patch of material using the trephination devices described herein can be at least 100 microns up to about 1500 microns, or between 100 microns up to 1200 microns, or between 100 microns and 900 microns, or between 300 microns and 600 microns. The stent trephined from a patch of material can have a width of at least about 100 microns and a width of no more than 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, no more than 800 microns, no more than 700 microns, no more than 600 microns, no more than 500 microns, no more than 400 microns, no more than 300 microns, or no more than 200 microns. The length of the stent trephined from a patch of material can vary depending on the location of stent implantation. In some implementations, the stent has a length that is between 1 mm and 10 mm, or more preferably between 3 mm and 8 mm long. The thickness of the stent trephined from the patch of material can be from 100 microns up to about 800 microns, or from 150 microns up to about 600 microns. In an implementation, the biological material forming the stent can have a thickness that is no smaller than 100 microns and no larger than 5 mm. The thickness of the stent can also depend on whether the stent is folded or rolled upon implantation such that a patch of material having a thickness of just 250 microns can cut into a stent and the stent folded at implantation to double the thickness to about 500 microns. The thickness of the stent can also depend upon what biologically-derived material is used. For example, scleral tissue or corneal tissue can often have a thickness of around 400 microns, but following harvest can shrink to about 250-300 microns. As such, a stent cut from a shrunken patch of corneal tissue may have a thickness of just 250 microns. In some implementations, which is described in more detail below, the stent cut from the patch of material is cut so as to substantially fill the conduit through which it is advanced for delivery.

In a non-limiting example, bio-tissue stent has dimensions no smaller than 0.1 mm and no larger than 8 mm in any direction and a thickness of not smaller than 50 microns and not larger than 8 mm. In a non-limiting example, the stent is about 6 mm in length by 300-600 microns wide by 150-600 microns thick. The trephination can be no smaller than 1 mm and no larger than 8 mm in any direction. In a non-limiting example, the trephined tissue has dimensions of 100-800 microns in width and 1 mm-10 mm in length. It should be appreciated that multiple stents may be delivered to one or more target locations during an implantation procedure.

The trephining devices described herein provide accurate and precise cutting without wrinkling. The trephining device can incorporate an anterior-to-posterior capture such that the material to be cut is held fixed on the z-plane preventing movement prior to engaging the tissue with a cutter. In implementations described in more detail below, the material to be cut is held fixed, compressed, and/or tensioned prior to cutting.

FIGS.2A and2Bshow example implementations of a trephination device205. The intraoperative trephination device used to form the stent can be combined with or removably coupled to a delivery device, such as an applier/injector for delivery to the implanted location.FIGS.3-4,FIGS.13A-13B, andFIGS.18A-18Bshow implementations of a trephination device integrated with a delivery device. The trephination devices can be a cartridge that removably couples to the delivery device as shown inFIGS.5, and6A-6B. The cartridge containing the patch of a material can be coupled to a distal portion of the delivery device as shown inFIG.5andFIGS.6A-6B. In this implementation, the cartridge can be removed from the delivery device prior to deployment of the stent to the eye. The cartridge containing the patch of a material can alternatively be coupled to a proximal portion of the delivery device. In this implementation, the cartridge need not be removed prior to delivery of the stent into the eye and the stent cut from the patch of material can be deployed from the cartridge coupled to the delivery device without a separate step.

The trephination device is configured to cut or otherwise form the biologically-derived tissue or patch of a material having a first contour or shape (e.g., a wider, square sheet or patch of material) into a second contour or shape (e.g., a narrower, rectangular strip of material) that conforms to an implantable stent having the dimensions described herein. The cutting performed using the trephination devices described herein can involve guillotine, punch, rotating, sliding, rolling, or pivoting blade cutting motion. In some implementations, the cutting is performed orthogonal to the plane of the patch of material. In some implementations, the cutting is performed axially along the conduit of implantation. As such, the axis of trephination can be aligned, within, or parallel to the implantation conduit to allow unimpeded tissue loading and transfer for implantation without manipulating, tearing, or damaging the fragile stent tissue. The trephination process can be preceded by a tissue fixation step wherein the biologically-derived tissue that forms the stent is firmly fixed between two appositional planar surfaces to ensure the tissue is not wrinkled or malformed and the subsequent trephination cut is of accurate dimensions. The fixation can optionally provide tension or stretching of the tissue within at least one plane to ensure clean cutting through the tissue.

The trephination can be performed along or within a path or conduit formed within the structure, such as within a cartridge, the delivery device, or within any other structure. The trephination of the patch of material can simultaneously or subsequently position the implant within or aligned with a conduit (e.g., the lumen of the delivery shaft) so that the cut implant can be delivered to the eye through the conduit without the cut implant needing to be transferred to a separate delivery device. In some implementations, the cutting motion can be from above the patch of material such that the sharp edges of the blades cut the patch of material from an upper surface of the patch. As the cutter slides through the patch of material forming the implant it can then urge the cut implant down into the lumen of the delivery shaft along an axis orthogonal to the longitudinal axis A of the handle. In other implementations, the cutting motion can be along the longitudinal axis A of the handle sliding through the patch of material from a proximal end towards a distal end of the handle305. The motion of the cutting can result in a cut implant already properly positioned and/or aligned with the delivery conduit of the delivery shaft. The cutting member can be movable relative to the handle as well as to a recess holding the patch of material into a cutting configuration. As the cutting member moves towards the cutting configuration it can cut the patch of material being held fixed within the recess forming the implant and the implant, once cut, can be axially aligned with the conduit for delivery.

The method of preparing an implant for implantation into an implant and for inserting the implant into the eye of patient can include inserting a patch of a material into a proximal portion of an instrument. The instrument can include the cutting member and a distal portion sized for insertion into the eye. Cutting the patch with the cutting member can form the implant. The implant, which can have a longitudinal axis, can align with a longitudinal axis of the lumen of the cutting member that cut the implant as the cutting member finishes cutting the patch of material to form the implant.

The implant can then be advanced from the proximal portion of the instrument into a deployment position in a lumen of an elongate tubular member of the distal portion of the instrument. The distal portion of the instrument is insertable into the anterior chamber of the eye so that it may be positioned adjacent eye tissue within which the implant is deployed from the instrument into the eye tissue. For example, the distal portion of the instrument can be inserted ab interno into the anterior chamber through a corneal incision, while the proximal portion of the instrument remains outside the eye. It should be appreciated that the distal portion of the instrument can be useful for other delivery pathways (e.g., trans-scleral delivery). Deploying the implant into the eye tissue can include the implant residing at least in part between a ciliary body and a sclera of the eye. The implant can reside between the ciliary body and the sclera within a cyclodialysis cleft.

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

The structure desirably trephines the tissue in a manner such that the tissue can be slid, pushed, and/or pulled along the conduit toward an implanted location of the eye. In other implementations, the stent is held fixed in place and the conduit withdrawn from the stent leaving the stent implanted within the eye. The conduit can be incorporated into or coupled to a delivery device that implants and deploys the stent into the eye. The trephination device can be made of any of a variety of materials, such as a hard material including a plastic and/or a metal.

The trephination device205shown inFIGS.2A-2Bcan have an internal lumen or enclosure210sized and shaped to form the elongated contour of the stent105when tissue is positioned within the enclosure210. The enclosure210has a dimension that approximates within microns the size of the stent105to be formed. The trephination device205is configured to stabilize tissue during the trephination process. In this regard, the trephination device205can fix the tissue in place and prevent movement of the tissue relative to the trephination device205as the tissue is trephined. In an implementation, the trephination device205can have one or more wings215configured to articulate between an open (FIG.2A) and closed (FIG.2B) configuration. A patch of material can be placed within the enclosure210when the trephination device205is in the open configuration. One or more blades220may be positioned on an inner surface of the wings215such that when the wings215are articulated to the closed configuration and the patch of material is in place within the enclosure210, the patch is cut into a stent having a desired dimension.

The enclosure210of the trephination device205can transition to and/or contain a corresponding lumen of a delivery device110that is configured to advance or otherwise inject the stent105into the eye. In an embodiment, the trephination device205trephines or cuts the tissue along a path that is aligned with or coaxial with a delivery pathway of the stent into the implanted location. For example, the stent cut from the patch of material held within the enclosure210can be urged distally through a lumen extending through a forward-end222of the trephination device205into a delivery device shaft. As such, the stent can be trephined first using a stand-alone trephination device. The trephination device holding the trephined stent can then be loaded into a delivery device, which is designed to accept the trephination device. This allows for loading the stent and deploying the stent without having to remove the stent from the trephination device in order to load it into the delivery device.

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

With reference again toFIG.1, a delivery device110is configured to be removably coupled to the stent105and used to deliver the stent105into the implanted location via an ab interno delivery pathway. The delivery device110is schematically represented inFIG.1. When coupled, the delivery device110can be inserted into the eye and used to implant the stent105in the implanted location via an ab interno delivery pathway.

The delivery devices described herein can prepare an implant and perform ab interno insertion of the implant into the eye.FIG.3shows a perspective view of an example implementation of a delivery device110having integrated trephination.FIG.4shows a cross-sectional view of the delivery device110ofFIG.3. The delivery device110can include a proximal handle305that is sized and shaped to be grasped by a single hand of a user. One or more actuators315can be positioned on a region of the handle305. The actuator315can also be manipulated by the single hand of the user such as with a thumb or finger. The actuator315can be one or more of a knob, button, slider, or other interface configured to move one or more components of the delivery device110as will be described in more detail below.

An elongated shaft310(also referred to herein as an applicator or delivery body) extends in a distal direction outward from the handle305. At least a portion of the shaft310contains or is coupled to the stent105for direct stent implantation. At least a portion of the shaft310extends along a longitudinal axis A. The shaft310can be angled, curved, or flexible at a distal end region such that it can form a distal curve or a bend. In some implementations, the shaft310can include a flexible portion and a rigid portion such that depending on relative position of the portions results in a change in shape of the shaft. The shaft310can be curved along at least its length and/or can be flexible.

The shaft310of the delivery device110has a size and shape is configured for ab interno delivery through a clear corneal incision to permit passage of the stent105out the distal end of the shaft310and left within the eye. In at least some methods, the distal end of the shaft310is sized to extend through an incision that is about 1 mm in length. In another implementation, the distal end of the shaft310is sized to extend through an incision that is no greater than about 2.5 mm in length. In another implementation, the distal end of the shaft310is sized to extend through an incision that is between 1.5 mm to 2.85 mm in length. In some implementations, the maximum outer diameter of the shaft310is no greater than 1.3 mm. The distal-most tip316of the shaft310can be blunt or sharp. A blunt distal-most tip316of the shaft310allows for dissecting between tissues of the eye without penetrating or cutting the tissues for positioning the stent105. For example, the distal-most tip316of the shaft310can be configured to bluntly dissect between the ciliary body CB and the sclera S (e.g., the supraciliary space) while the stent105remains fully encased within the shaft310during the blunt dissection. In an alternative implementation, the distal-most tip316of the shaft310has a sharp cutting configuration for dissecting application and implantation through the scleral wall into the subconjunctival space. In yet another embodiment, the distal-most tip316can have a cutting configuration for dissecting and implantation into the Schlemm's canal or trans-sclerally.

The stents described herein are formed as solid strips of material without any lumen. Thus, the stents are not deliverable over a guidewire as many conventional glaucoma shunts are. Additionally, the stents are formed of relatively soft tissue that is more fragile as typical shunts formed of more rigid polymeric or metal material. More rigid shunts can be implanted such that a distal end of the shunt is used to create a blunt dissection at the interface of the tissues through which the shunt is being inserted. The stents described herein are preferably deployed using a retractable sleeved type of injector that once in proper anatomic position can be retracted leaving the stent more gently externalized and position. Additionally, the stents described herein can be deployed in the eye by urging the stent distally through at least a portion of the shaft310. The stents can have a dimension that substantially fills an inner lumen of the shaft310(or the inner lumen of at least a portion of the shaft310through which it is delivered) such that the stent may be urged distally through that portion without wrinkling or being damaged. The tolerance between the outer dimensions of the stent105and the inner dimension of the conduit can be up to about 200%. The conduit can also be coated with a lubricious material (e.g., Teflon) to improve advancement of the stent105through the conduit during deployment.

The shaft310can define an internal, hollowed shape for containing the stent105. In some implementations, the shaft310can be formed of an outer tube318(also referred to herein as a tubular outer sheath) and an inner pusher320(also referred to herein as an elongate member) positioned within the lumen of the outer tube318(seeFIG.4and alsoFIGS.7,11C-11E). Movement of the outer tube318and/or the pusher320can act to deploy the stent105within the eye. The outer tube318and pusher320of the shaft310can be operatively coupled to the one or more actuators315in order to deliver a stent105to the eye. The outer tube318can be fixed relative to the handle305and the pusher320moveable relative to the handle305. The outer tube318can be movable relative to the handle305and the pusher320fixed relative to the handle305. Alternatively, both the outer tube318and the pusher320can be movable relative to the handle305. Motion of the outer tube318and/or the pusher320can be generated using the same actuator315or different actuators315on the handle305that can be actuated by a user moving the actuator315relative to the handle305. The type of movement of the actuator315relative to the handle305can vary, including sliding or rotatable movement. The implementation shown inFIGS.3and4can include a shaft310having an outer tube318and a pusher320. The outer tube318can be coupled to a slider and the pusher320can be coupled to a knob311at a proximal region of the handle305.

Once the desired position in the tissues is reached with the distal end of the shaft310, the stent105is left in position in the eye and the shaft310withdrawn. In an implementation, the outer tube318of the shaft310is retracted, for example, using the actuator315on the handle while the pusher320remains stationary relative to the handle305. The pusher320therefore can act as a stopper thereby preventing the stent105from following the outer tube318as it is retracted. The result is that the stent105is unsheathed from the shaft310and left within the tissues.

The delivery device110can further include a cutting member312(seeFIG.4), such as a blade or cutter tube, that can move relative to the handle305to cut tissue thereby forming the stent105. As mentioned above, the stent105can be formed from a patch of material. The patch of material may be loaded within a region of the delivery device110and cut into a smaller stent shape at the time of delivery. The cutting member312can be actuated by a user to create the stent from the patch of material.

In an example embodiment, the cutting member312is attached to a cover314that is movable relative to the handle305(seeFIGS.3-4). The cover314can be coupled to a distal end region of the handle305by a hinge317such that the cover314can rotate around a pivot axis P of the hinge317relative to the handle305. The cover314can be lifted to pivot into an open configuration (seeFIG.3) revealing a recess321within which a patch of material101can be positioned and held fixed relative to the handle. When the cover314is rotated back around the pivot axis P into the closed configuration, the patch of material101positioned within the recess321is compressed and/or tensioned between the cover314and the handle305. The compression and/or tension of the patch of material101can help to assure a clean and complete cut of the material. In some implementations, the patch of material101is placed under tension such as by outward stretching by the cover314prior to cutting with the cutting member312. The patch of material101may be stretched outward from the cutting locations as shown inFIGS.15A-15C.

The recess321can be within a proximal portion of the instrument such as with a portion of the handle305. The recess321for holding the patch of material101may also be a recess within a cartridge removably coupled to a portion of the instrument, such as within a region of the handle305or coupled to a distal portion of the instrument.

It should be appreciated that tensioning the patch can include activating a separate actuator to tension the patch. Tensioning can also be achieved during the stabilization and compression step without a separate actuation. For example, closing the cover314alone may result in both compression and tensioning of the patch of material without a separate actuator to provide the tension on the patch of material after compression.

The cover314can open along any of a number or orientations relative to the handle. For example, the pivot axis P of the hinge317can be substantially orthogonal to the longitudinal axis of the handle A. In this implementation, the hinge317can be positioned on a distal end of the handle305between the shaft and the cover314such that the cover314hinges open by rotating upward and toward the shaft (see, e.g.,FIGS.3and4). Alternatively, the hinge317can be positioned such that the cover314hinges open by rotating upward and toward the proximal end region of the handle305(see, e.g.,FIGS.5and6A-6B) In still other implementations, the hinge317can be positioned on a side of the handle305such that the pivot axis P and the longitudinal axis A are substantially parallel with one another. In this implementation, the cover314can swing outward away from the longitudinal axis A of the handle305(see, e.g.,FIGS.15A-15C). Any of a variety of configurations are considered herein.

The cutting member312can extend from a lower surface of the cover314to cut the patch of material101(e.g. bio-tissue) in a guillotine type manner.FIG.4shows the cover314in an open configuration raised away from the recess321within which a patch of material101is positioned. The cutting member312can extend from a lower surface of the cover314such that its cutting surface penetrates the patch of material101. In some implementations, the cutting member312is coupled to a movable actuator or push-button313that can be actuated to move the cutting member312from a sheathed configuration towards a cutting configuration. Once the cover314is in a closed configuration compressing and/or stretching the patch of material101between the lower surface of the cover314and the housing305, the movable actuator313may be urged downward relative to the cover314placing the cutting member312into a cutting configuration. The cutting member312can extend below the lower surface of the cover314and slice through the patch of material101held within the recess321. One of more return springs323can urge the actuator313back upward such that the cutting member312is once again in the sheathed configuration. The cutting member312cuts the patch of material into an implant as the cutting member moves towards the cutting configuration. The implant, once cut, is also axially aligned with the lumen of the shaft.

It should be appreciated that other types of cutting mechanisms can be used. For example, lowering of the cover314may also cut the patch of material101held within the recess321in a rotating type cutting motion. In this implementation, the cutting member312extends below the plane of the lower surface of the cover314such that the blade edges are available to cut the patch of material101upon rotating the cover314into the closed configuration. Alternatively, the cutting motion may be an axial cutting motion with a slidable cutting tube such that trephination occurs along the implantation conduit as opposed to a cutting motion orthogonal to the plane of the patch of material101.

As mentioned above, as the cutting member moves towards the cutting configuration it cuts the patch of material into an implant. The implant, once cut, is also axially aligned with the lumen of the shaft for deployment into the eye. Thus, motion of the cutting member312simultaneously cuts the stent and places the cut stent into a position relative to the shaft310such that the stent can be delivered through the shaft310. The cutting member312in order to cut the patch of material101into a rectangular stent shape can include a pair of blades separated by a spacer. The spacer between the pair of blades can engage with the cut stent105following cutting by the blades to urge the stent105downward through a slot in the outer tube318. The pusher320can be in a fully retracted configuration via the knob311such that the lumen of the outer tube318is free to accept the cut stent105through the slot. It should be appreciated that the stent105may be urged downward into a position relative to the delivery device that aligns the stent105with the path of implantation while not specifically loaded into the lumen of the outer tube318. For example, loading into the lumen of the outer tube318can occur upon an additional step such as advancement of the stent105towards the lumen of the outer tube318following cutting. A variety of sheath loading configurations is considered herein, including top-loading as described above, front-loading, rear-loading, and side-loading, which will be described in more detail below. Regardless of the configuration, the trephination of the patch of material101can place the stent105in a position (i.e. axially aligned with the lumen of the shaft) that allows for it to be deployed into the eye without necessitating manual tissue transfer of the tiny piece of cut material.

FIG.5shows another implementation of a delivery device110. This implementation has a detachable trephination cartridge205close to the tip of the delivery device110. This implementation reduces or minimizes a travel distance of the stent105once the stent has been formed within the lumen of the shaft310.

As with the previous implementation shown inFIGS.3and4, the delivery device110can include a proximal handle305having one or more actuators315and a shaft310extending from a distal end region of the handle305. The actuators315can include a first and second slider configured to move the outer sheath and the pusher of the shaft310, respectively. It should be appreciated that the device110need not incorporate multiple actuators315to achieve motion of multiple components. For example, the device110can include a single actuator315configured to cut and deploy the stent105, for example by causing motion of both the outer sheath and pusher based on, for example, the degree of actuation of the slider.

The trephination cartridge205can include a base324and a cover314movably attached to the base324. The cover314and base324can be coupled together by a hinge317such that the cover314rotates around a pivot axis of the hinge317. As with the previous implementation, the cover314can be lifted to pivot into an open configuration revealing a recess321of the base324within which a patch of material can be positioned and held fixed. When the cover314is rotated back around into the closed configuration, the patch is compressed and/or tensioned between the cover314and the base324. The cover314and base324need not be hinged relative to one another. For example, the cover314and base324can simply uncouple revealing the upper surface of the base324such that the shaft310and patch of material101can be positioned appropriately relative to the trephination cartridge205. The cover314can be configured to additionally apply an amount of tension on the patch of material101, such as stretching in an outward direction from the center of the patch of material101to improve cutting.

FIG.6Ashows the delivery device110having a trephination cartridge205coupled to a distal end region of the handle305in a closed configuration in which an upper surface of the base324and a lower surface of the cover314of the trephination cartridge205are opposed against one another.FIG.6Bis a cross-sectional view of the device110inFIG.6Aillustrating the shaft310extending through the handle305.

The trephination cartridge205can be provided pre-loaded with a patch of material positioned within the recess. For example, the patch of material can be compressed and/or tensioned within the base324and cover314. The cutting member312can then be actuated to punch out a stent105from the patch of material, for example, by pressing down on the push-button313to urge the cutting member312through the patch of material held within the trephination cartridge205. The delivery device110and trephination cartridge205can then be engaged to each other. For example, the shaft310can insert through a proximal port on the trephination cartridge205thereby front-loading the cut stent105into the outer tube318for delivery into an eye. The cut stent105can be held fixed within the trephination cartridge205. In still further implementations, the stent can be loaded into a cutout opening in the shaft from above, or front-loaded, or from a rear of the shaft.

It should be appreciated that the patch of material need not be cut into the stent by a user at the time of implantation into a subject. The patch of material may be cut into the stent well before the time of implantation, such as at the tissue bank or tissue engineering lab. The stent can be provided as a pre-cut, pre-loaded stent within a cartridge configured to couple with the delivery device. For example, the trephination cartridge205can be provided to a user pre-loaded with a pre-cut stent105from the patch of biologically-derived material. The cartridge205holding the stent105can be coupled with the delivery device at the time of implantation. Once coupled together, a user can load the stent105into the shaft310of the delivery device as described elsewhere herein. In still further implementations, the stent105can be provided to a user pre-loaded within the lumen of shaft310. The patch of material can be provided in the cartridge or in the lumen of the shaft310emerged in an appropriate tissue preservative media as is known in the art.

In an implementation, the user can manually load a patch of material101through opposing cut-out windows326extending through the outer tube318of the shaft310of the delivery device110(seeFIG.7). The cut-out windows326in the outer tube318can extend through opposing sidewalls such that the patch of material101can be inserted through a first cut-out window326, traverse the lumen328of the outer tube318, and insert through the second cut-out window326on the opposite side of the lumen328. The dimensions of the cut-out326are sufficient to load the patch of material101through the cut-out326as shown inFIG.7. The patch of material101can have a dimension that is wider than an outer diameter of the outer tube318such that each side of the patch101extends beyond the sidewalls of the outer tube318. The cut-out windows326in the outer tube318can each have a length along the longitudinal axis A of the shaft310that is at least as long as a length of the patch of material101. The cut-out windows326in the outer tube318can have a depth that is at least as thick as the thickness of the patch of material101.FIG.8Ais a top-down schematic view of the cut-out windows326of the shaft310.FIG.8Bis a cross-sectional view ofFIG.8Ataken along line B-B. The cut-out windows326, which can be created by removing a side wall on either side of the outer tube318), form narrow webs330on an upper and lower surface of the tube318.

FIGS.9A-9Bshow another implementation of a trephination cartridge205having a cover314and a base324.FIG.9Ashows the base324with the top cover314installed.FIG.9Bis a cross-sectional view of the cartridge205showing the tissue patch101sandwiched between the base324and the cover314.FIG.9Cshows the base324of the trephination cartridge205loaded with a patch of material101loaded within the cut-out windows326of the tube318and positioned within the recess321of the base324. The recess321can be positioned between a proximal slot332and a distal slot334. The proximal slot332is sized to receive at least a portion of the outer tube318located proximal to the cut-out windows326and the distal slot334is sized to receive the portion of the outer tube318located distal to the cut-out windows326. The recess321can have any of a variety shapes, but is generally sized to receive the patch of material101loaded within the cut-out windows326of the outer tube318. Thus, when the shaft310of the delivery device110is inserted into the trephination cartridge205, the shaft310is received within the proximal and distal slots332,334and the tissue patch101sits within the recess321.

Still with respect toFIGS.9A-9C, the cover314can have an upper surface forming an external surface of the cartridge205. The cover314can also include a lower surface configured to engage with an upper surface the cartridge base324. The upper surface can include a recess336within which is an entrance to a bore338extending from the upper surface through a full thickness of the cover314to the lower surface. The upper surface of the cartridge base324includes an entrance to a bore340extending through at least a thickness of the base324. The bore340of the base324can, but need not extend through the full thickness of the base324. When the cover314abuts the base324, the bores338,340are aligned such that a contiguous channel is formed. The contiguous channel is sized and shaped to receive the cutting member312, which will be described in more detail below. The cutting member312can translate relative to the cartridge205and extend from the upper surface of the cover314through the full thickness of the cover314into the bore340of the base324.

The lower surface of the cover314surrounding the bore338in the cover314and the upper surface of the base324surrounding the bore340in the base324can compress the patch of material101positioned therebetween. The recess321in the base324can have a depth that is less than a thickness of the patch101positioned within the recess321such that when the cover314is coupled to the base324, the patch of material101is compressed between the cover314and base324. The compression of the patch of material101between the base324and the cover314helps to prevent movement of the patch of material101during cutting with the cutting member312. Tension can also be applied to the patch of material101prior to cutting. In some implementations, the cover314is hinged relative to the base324(seeFIG.5). The cover314and base324can be reversibly fixed to one another such that upon closing the cover314onto the base324, the cover314latches or otherwise reversibly couples to the base324to prevent inadvertent opening of the cover314relative to the base324.

FIG.10Aillustrates the trephination cartridge205with the base324and cover314in a closed configuration.FIG.10Bis a cross-sectional view of the trephination cartridge205in a closed configuration with the patch of material101sandwiched between the cover314and base324and the cutting member312inserted into the bore338of the cover314.FIG.10Cis a cross-sectional view of the trephination cartridge205with the cutting member312advanced fully through the cover314and into the bore340of the base324.

The cutting member312can include a pair of blades344and an enlarged grip feature or handle343. The handle343is positioned on an upper end of the blade housing342whereas the pair of blades344project from a lower end of the blade housing342. The handle343can be shaped and sized for a user to comfortably grip the cutting member312.FIGS.10A-10Cillustrates the handle343as having a disc shape configured to be received within the correspondingly shaped recess336in the upper surface of the cover314. Any of a variety of shapes are considered herein.

The blade housing342can include a central channel346within which an upper portion of the blades344are received. The lower cutting surfaces of the blades344extend below the blade housing342. The pair of blades344can be separated from one another by a spacer345defining a gap between the blades344. The gap size is selected based on the desired width of the stent105to be achieved upon cutting the patch of tissue101with the blades344.

The cutting member312can be received within the recess336in the cover314such that the blades344extending from a lower end of the cutting member312insert first through the bore338in the cover314followed by the blade housing342(seeFIG.10A). Thus, the bore338of the cover314can be sized and shaped to receive not just the blades344, but also at least a portion of the blade housing342. The handle343can be sized and shaped to be received within the recess336in the cover upon full insertion of the cutting member312within the cartridge205.

The tissue patch held within the cut-out region of the shaft is cut in two locations creating a narrow strip of material (i.e. the stent105) from the patch of material101. As the cutting member312is urged further through the bore338in the cover314, the blades344are urged towards the patch of material101compressed between the cover314and the base324(seeFIG.10B). As the cutter is urged further through bore338of the cover314and enters bore340of the base324, the blades344slice through the patch of tissue101positioned within the recess321(seeFIG.10C). The blades344make two cuts in the patch of material101as it extends down through bore340of the base324completely cutting through the patch101forming a stent105. Motion of the cutter towards the cutting configuration cuts the patch of material into the stent as the cutting member moved towards the cutting configuration and the stent, once cut, is axially aligned with the lumen328of the outer tube318. The stent105that is formed is thereby already loaded relative to or within the lumen328of the outer tube318such that no loading step is necessary.

The blades344have inserted through the contiguous channel formed by the bores338,340of the cover314and the base324. The housing342can seat within the bore338and/or the handle343can seat within the recess336of the cover314thereby preventing any further downward motion of the blades344. The stent105that is formed is held snugly within the lumen328of the outer tube318. As mentioned above, the outer tube318of the delivery device shaft310can include a pair of cut-out windows326on opposing sidewalls creating narrow webs330on an upper and lower surface of the tube318. As best shown inFIGS.11A-11E, each of the blades344is received within a respective cut-out window326of the tube318when the cutting member312is inserted within the cartridge205so that the blades344extend into the bore340in the base324. The gap between the pair of blades344is sized to accommodate and receive the webs330as the blades344slide past the shaft318positioned within the cartridge205. The stent105once cut is contained within the lumen328of the outer tube318at the location of the cut-out windows326with one of the pair of blades344enclosing the stent105on a first side and a second of the pair of blades344enclosing the stent105on a second opposite side. The enclosure creates the path for the stent105to be deployed from lumen328out the distal end of the shaft310, which will be described in more detail below.

Still with respect toFIGS.11A-11E, the blades344can include single bevel edges that are angled to propagate the cut, similar to scissors. It is preferred that the blades344not chop tissue. The blades344are positioned relative to the cartridge205such that a complete cut through the patch101occurs upon full travel of the cutting member312through the cartridge205.

Upon complete translation of the cutting member312into the cover314(i.e., placement of the cutting member312into the cutting configuration), the blade housing342is constrained within the bore338in the cover314. Thus, a length of the blade housing342is no longer than and preferably slightly shorter than a depth of the bore338in the cover314. In some implementations and as best shown inFIG.10B, the distal exit from the bore338at the lower surface of the cover314can have a smaller dimension than the entrance to the bore338. Where the entrance to the bore338is sized to receive the blade housing342, the exit from the bore338may be sized to receive only the blades344and not the blade housing342. This arrangement can prevent over-insertion of the cutting member312relative to the cartridge205in that the lower end region of the bore338acts as a stop for the blade housing342.

The cutting member312can additionally include a safety sheath (not shown) configured to enclose the dual blades344extending from a lower end of the blade housing342. The safety sheath can prevent inadvertent damage to the blades344or the user when the cutting member312is not engaged with the cartridge205. For example, the safety sheath can enclose the blades344on all but a lower end of the cutting member312. The cover314and base324of the cartridge205can include additional channels aligned, sized and shaped to receive the safety sheath surrounding the blades344as the cutting member312is inserted into the cartridge205.

FIG.11Eshows a cross-sectional view of the cut-out windows326of the outer tube318with the blades344positioned on either side of the upper and lower webs330. As mentioned, the shaft310of the delivery device110can include a pusher320positioned within the lumen328of the outer tube318. At least a portion of the pusher320can have a cross-sectional shape configured to slide past the blades344positioned within the cut-out windows326of the tube318. The cross-sectional shape of at least a portion of the pusher320can incorporate flat sides configured to align with the cut-out windows326upon extension of the pusher320relative to the outer tube318during deployment of the stent105from the lumen328. The flat sides of the pusher320(as opposed to convex sides) can define a width that is sized to slide between the two blades344positioned within the cut-out windows326. Like the stent, at least a portion of the pusher320can be sized to completely fill at least a portion of the lumen328of the outer tube318. The outer tube318can be a hypotube that is no greater than about 18 G (0.050″ OD, 0.033″ ID), 20 G (0.036″ OD, 0.023″ ID), 21 G (0.032″ OD, 0.020″ ID), 22 G (0.028″ OD, 0.016″ ID), 23 G (0.025″ OD, 0.013″ ID), 25 G (0.020″ OD, 0.010″ ID), 27 G (0.016″ OD, 0.008″ ID), 30 G (0.012″ OD, 0.006″ ID), or 32 G (0.009″ OD, 0.004″ ID). In some implementations, the outer tube318is a hypotube having an inner diameter that is less than about 0.036″ down to about 0.009″. The dimensions of the outer tube318can be selected based on the dimensions desired for the stent to be implanted as discussed in more detail above.

While the shaft310of the delivery device110is installed in the cartridge205and the blades344are still positioned in the cutting configuration, the pusher320can be pushed distally away from the handle305of the delivery device110to position the stent105cut from the patch of material101into a primed position within the lumen328. In some implementations, the pusher320can be advanced distally relative to the handle305, for example, using an actuator315on the handle305. The presence of the blades344on either side of the cut-out windows326and the webs330on the upper and lower sides prevents the stent105from buckling within the lumen328during this priming step. The conduit within which the stent105is held is size-matched to the outer dimension of the stent being implanted thereby preventing buckling and wrinkling as the stent105is urged into the primed position.

Once the stent105is urged into the distal tip region of the outer tube318, the blades344can be retracted from the base324. In some implementations, the cutting member312can be removed from the cartridge205and the cover314opened relative to the base324so that the shaft310of the delivery device110can be removed from the cartridge205. In other implementations, the cutting member312can be withdrawn from the base324, but still engaged with the cartridge205for the shaft310of the delivery device110to be removed from the cartridge205. The shaft310can be withdrawn from the cartridge205with or without the cover314being in an open configuration. Once the delivery device110and the cartridge205are disengaged with one another, the delivery device110is ready to be used to insert the stent105into the eye, which will be described in more detail below.

As mentioned above, movement of the components of the delivery device110can be achieved using one or more actuators315of the handle305.FIG.6Bis a cross-sectional view of an implementation of the delivery device110having its distal shaft310engaged with a trephination cartridge205. The shaft310can include a pusher320and an outer tube318. The pusher320can be coupled to a first actuator315and the outer tube318can be coupled to a second actuator315. Each of the first and second actuators315can be sliders configured to advance and retract their respective components. The first actuator315can be withdrawn proximally such that the pusher320is in its most proximal position relative to the outer tube318during cutting of the patch of material101compressed and/or tensioned within the cartridge205. Once the patch of material101is cut, the user can advance the first actuator315to urge the pusher320distally to prime the stent105within the lumen328of the outer tube318towards the distal end of the shaft310. After the cut stent105is primed into its distal position within the lumen328, the cartridge205can be disengaged from the shaft310. The outer tube318of the delivery device110can be used to dissect tissue of the eye until a target location is accessed. Once the delivery device is in position to deploy the stent105in the eye, the first actuator315coupled to the pusher320can be maintained in this distal position and the second actuator315withdrawn to retract the outer tube318. This relative movement of the outer tube318to the pusher320deploys the stent105from the lumen328in the anatomy (as shown inFIG.12B). It should be appreciated that additional distal movement of the pusher320can be used to aid in deployment of the stent105from the lumen328. It should also be appreciated that pusher320advancement and outer tube318retraction can be controlled by dual actuators315as described above or by a single actuator315capable of both pusher and outer sheath movement depending on degree of actuation. Additionally, the shaft310of the delivery device110can be used to inject viscoelastic during the procedure using the pusher320as a plunger.

FIGS.13A-13BandFIGS.18A-18Bshow interrelated implementations of a delivery device1110having integrated trephination forming a system for preparing an implant and performing ab interno insertion of the implant into the eye. As described elsewhere herein, the delivery device1110can be inserted into the eye and used to implant the stent105in the implanted location via an ab interno delivery pathway. The delivery device1110can include a proximal portion such as a proximal handle1305that is sized and shaped to be grasped by the user and remains outside of a patient's eye. The delivery device1110can also include a distal portion. The distal portion can include an elongate delivery shaft1310extending distally from the proximal handle1305. The elongate delivery shaft1310includes an outer tube1318having a lumen1328(seeFIG.14A). An axially movable cutter tube1312can be positioned within the handle1305. A pusher1320is shown positioned within the lumen1378of the cutter tube1312. The pusher1320is configured to be advanced distally through the lumen1328of the outer tube1318. It should be appreciated that where the delivery devices are described herein as suitable for performing ab interno insertion of an implant that other approaches for implantation are considered as well. For example, the delivery devices may be used to perform a trans-scleral approach for delivery of the implant.

Still with respect toFIG.14A, the delivery device1110can include an access door1314coupled to a region of the handle1305, such as by a hinge1317, so that the door1314can be rotated around the pivot axis of the hinge1317relative to the handle1305. When the access door1314is in an open configuration, a recess1321is revealed. The patch of material101may be loaded within the recess1321for cutting into a stent105prior to delivery. The pusher1320positioned within the lumen1378of the cutter tube1312is retracted proximally relative to the recess1321such that the patch of material101may be positioned within the recess1321.FIG.14Bshows the access door1314rotated to a closed configuration capturing the patch of material101within the recess1321. In some implementations, the access door1314can be formed of a transparent or translucent material such that the patch of material101positioned within the recess1321may be visualized by a user following loading (see alsoFIG.18A). The access door1314can also include one or more latches1322(seeFIG.19A) to ensure once the door1314is closed it remains closed until a user desires to open the door1314again. In some implementations, the latch of the access door1314can include interference fit features or magnets, or other element.

The recess can be within a portion of the instrument such as within the handle as described above. The recess may also be within a cartridge removably coupled to the instrument. The cartridge can be coupled to a distal portion of the instrument as shown herein and removed prior to deployment in the eye. The cartridge can also be coupled to a proximal portion of the instrument and may or may not be removed prior to deployment.

When the door1314is rotated around the pivot axis P from an open configuration into a closed configuration, the patch of material101positioned within the recess1321can be captured, compressed, and/or tensioned. The door1314can be adapted to engage at least some portion of the patch of material before the patch is cut. The door1314can prevent movement of the patch during the cutting with the cutter.

In some implementations, at least a portion of the recess1321can have a depth, for example, the portion aligned with a centerline of the implantation conduit, that is less than the thickness of the patch of material101held within the recess1321. Upon closing the door1314, the patch of material101is compressed slightly.

At least a portion of the patch of material101can be placed under tension prior to cutting. The cutting achieved by the cutter tube1312is improved when the patch of material101is placed under slight tension before cutting. The tensioning of the portion of the patch can include compressing a first portion and a second portion of the patch and tensioning a central portion of the patch, the central portion located between the first and second portions. The central portion of the patch becomes the implant upon cutting the patch with the cutter tube1312.

Tensioning the portion of the patch can include activating an actuator to tension the portion of the patch. Activating the actuator can include rotate an actuator to tension the portion of the patch. For example, the cover can include an actuator and actuation of the actuator can tension at least a portion of the patch. However, tensioning need not be a separate actuation. As discussed elsewhere herein, closing the access door1314can provide both fixation and an amount of tension on the patch.FIGS.15A-15Care cross-sectional schematic views of the handle1305showing the access door1314and the patch of material101positioned within the recess1321. The door1314can include a feature configured to apply a small amount of tension or stretching force onto the patch of material101to improve cutting. The door1314can be coupled to a stretcher1350having a pair of flexible stretcher legs1352. The stretcher legs1352extend into the recess1312until each of the feet1354at the end of the legs1352contact the patch of material101(seeFIG.15B). One foot1354can contact a first portion of the patch of material101on a first side of the center line and an opposite foot1354can contact a second portion of the patch of material101on a second, opposite side of the center line. The stretcher1350can be actuated from a first position in which the stretcher1350is elevated relative to the recess1321. When the stretcher1350is urged downward, the stretcher legs flex and the feet1354are urged outward further away from the center line and away from one another (see arrows inFIG.15C). The distance between the feet1354is sufficient to allow for the cutter tube to slide through the recess1321between the feet1354in an axial direction to cut the patch of material101. The lower surface of the feet1354can have surface features1355, for example ridges, bumps, or other texture that optimizes the interface between the feet1354and the patch of material101. The surface features1355allow the feet1354to stretch the patch of material101outward as the feet1355are urged outward.

The stretcher1350can have any of a variety of configuration. The stretcher1350can be a button as shown inFIGS.13A-13B and15A-15C. The stretcher1350can be a dial as shown inFIGS.18A-18B,FIGS.19A-19B,FIGS.20A-20C,FIG.21, andFIG.22. Any of a variety of other actuators are considered that are configured to impart tension on the patch101. In implementations where the stretcher1350is a button the door1314can additionally incorporate a stretch release button1357(seeFIG.13A) to release the tension applied, if desired.

Regardless the configuration, the stretcher1350can have an upper end region1360and a lower end region1362(seeFIG.20A) The upper end region1360is configured to be gripped and actuated (i.e. pushed or rotated). The lower end region1362of the stretcher1350can engage with the access door1314.FIG.21shows an implementation of the stretcher1350that is a dial having threads1367on the lower end region1362of the stretcher1350that engage with corresponding threads1365of a bore1364in an upper surface of the door1314. Rotation of the stretcher1350relative to the bore1364draws the stretcher1350further down into the bore1364and urges the feet1354further into the recess1312.

As discussed elsewhere herein, tensioning the patch can include activating an actuator such as the dial to tension the patch. Tensioning can also be achieved without a separate actuation. For example, closing the door1314may achieve both fixation and tension of the patch of material without a separate actuator to provide the tension on the patch of material after compression. The door1314, therefore, can achieve a prefixed tension on the patch of material upon closure without a separate activation of the stretcher1350up or down relative to the material.

The recess1321receives the patch of material101. The recess1321can include a projection1371in the shape of an inverted V can project upward from a center line of the recess1321that urges the centerline of the patch of material101upward toward the door1314while allowing the sides of the patch of material101to hang downward into corresponding channels1370on either side of the centerline (seeFIG.19AandFIG.21). Upon closing the door1314, the stretcher legs1352extend into the recess1312until each of the feet1354of the stretcher legs1352contact the sides of the patch of material101hanging within the channels1370(seeFIG.21). One foot1354can contact a first portion of the patch of material101in a first channel1370adjacent the center line and an opposite foot1354can contact a second portion of the patch of material101in a second channel1370on the opposite side of the center line. When the stretcher1350is drawn further into the bore1364, such as by turning the dial, the feet1354urge these portions deeper into their respective channels1370thereby compressing the centerline of the patch of material101against the inverted V1371of the recess1321(seeFIG.21). The distance between the feet1354is sufficient to allow the cutter tube1312to pass between them. The inverted V1371can include a shallow central channel1372sized and shaped to receive the lower wall geometry of the cutter tube1312as the cutter tube1312is advanced distally to cut the patch of material101.

The cutting member can include a cutting member lumen, a distal opening, and a pair of opposed cutting edges. The cutting can include advancing the cutting member to cut a patch of material and capture the implant within the cutting member lumen. The pair of opposed cutting edges can cut the patch in two locations to separate the implant from a remainder of the patch of material. A distal portion of the cutting member can be beveled. The longitudinal axis of the implant can remain aligned with a longitudinal axis of the lumen of the cutting member as the cutting member finishes cutting the patch to form the implant.

The cutter tube1312can be a dual beveled hypotube forming two leading points1372(seeFIGS.23A-23D). The two leading points1372can be positioned above and below the patch of material101, respectively, as the cutter tube1312is advanced into a cutting configuration and slices through the patch of material101. The lower leading point1372can be received within the shallow central channel1372of the inverted V1371and the upper leading point1372glides over the patch of material101. The leading points1372can be blunt or sharp. The cutting surfaces of the cutter tube1312include the inside edges1374of each bevel1376. The inside edges1374are separated from one another by the lumen1378of the cutter tube1312so that the cutter tube1312slices the patch of material101in two locations. Thus, the inner diameter or distance between inside edges1374of the cutter tube1312determines the width of the stent105that is cut.

The stent105, once cut, is contained within the lumen1378of the cutter tube1312creating an enclosure for the stent105. The stent105can have a dimension that substantially fills the lumen1378of the cutter tube1312. The axial motion of the cutter tube1312in a distal direction towards the cutting configuration positions the cutter tube1312so that its walls bridge the recess1321and forms part of the implantation conduit1319. The lumen1378of the cutter tube1312can be coaxial (e.g., contiguous or non-contiguous) with the lumen of the elongate shaft1310through which the stent105will be delivered to the eye. For example, as shown inFIG.17B, the cut stent105may be advanced out of the cutter tube1312along the implantation conduit1319towards the distal end of the delivery shaft1310. Thus, the axial motion of the cutter tube1312along an axis of the implantation conduit1319simultaneously cuts the stent from the patch of material101and axially aligns the cut stent with or relative to the delivery shaft lumen such that the stent105may be deployed in the eye without any tissue transfer step.

The inner elongate member or pusher1320is movable relative to the delivery shaft lumen. The stent105can be pushed distally out from the cutter tube1312by the pusher1320. As discussed above, the elongate shaft1310of the delivery device1110can include an outer tube1318and an inner pusher1320positioned within the lumen of the outer tube1318. The pusher1320is sized and shaped to travel distally through the lumen1378of the cutter tube1312to urge the stent105towards the distal end of the outer tube1318(seeFIG.17B). In some implementations, the outer tube1318is fixed relative to the handle1305and the inner pusher1320is movable relative to the outer tube1318to deploy the stent105from the outer tube1318. In other implementations, both the outer tube1318and the pusher1320are movable relative to the handle1305and to each other. The distal end of the pusher1320can be shaped to atraumatically urge the stent105in the distal direction.

In still further implementations, the elongate delivery shaft1310can include a fixed outer tube1318and an introducer tube1380positioned and movable through the lumen1328of the outer tube1318(seeFIGS.18A-18B). The pusher1320, in turn, can be movable through the lumen1382of the introducer tube1380. The distal end region of the elongate tubular member for delivering the implant into the eye can be angled, curved, and/or flexible. In some implementations, the introducer tube1380can have a curved shaped at its distal end region and/or the introducer tube1380can be flexible to conform to a curved shape. The curved shape of the distal end region of the introducer tube1380can conform to a shape of the desired implantation location, such as the curvature of the eye near the anterior angle. The outer tube1318can be a rigid tube and the introducer tube1380can be flexible. The pusher1320can be a shape-set Nitinol that is takes on the shape of the rigid outer tube1318when retracted proximally and allowed to relax back into its shape-set configuration (i.e. having a curve or bend away from the longitudinal axis of the outer tube1318) when extended distally beyond the distal opening of the outer tube1318. The introducer tube1380can be flexible enough to take on the shape of the pusher1320when the pusher1320extends beyond the outer tube1318. Thus, the introducer tube1380can be more flexible than the pusher1320and the pusher1320can be more flexible than the outer tube1318. In some implementations, the introducer tube1380can be formed of silicone, thermoplastic elastomer, polyethylene, polypropylene, or a combination thereof. The introducer tube1380can have a degree of stiffness, but not so stiff that it is incapable of being retracted over the pusher1320during deployment.

The introducer tube1380and pusher1320can work together to deploy the stent105in the eye after the stent105is cut by the cutter tube1312. The pusher1320can urge the stent105out of the lumen1378of the cutter tube1312into the lumen1382of the introducer tube1380.FIG.24Ashows the introducer tube1380extending through the lumen1378of the cutter tube1312and extending a distance past the distal end of the outer tube1318. The stent105is positioned within the lumen1382of the introducer tube1380urged distally by the pusher1320also positioned within the lumen1382of the introducer tube1380. The stent105is urged distally through the lumen1382by the pusher1320until the stent105is positioned within the distal end region of the introducer tube1380(FIG.24B). At this stage of deployment, the pusher1320has advanced a distance beyond the distal end of the rigid outer tube1318such that the pusher1320can relax back into its curved or bent shape. The introducer tube1380, which can be more flexible than the pusher1320, takes on the shape of the pusher1320. The cut stent105in this primed position near the distal end of the introducer tube1380is ready to be implanted in the eye. The introducer tube1380can be retracted while the pusher1320remains stationary to effectively push the stent105out from the lumen of the introducer tube1380(seeFIG.24C).

Advancing the implant from the proximal portion of the instrument can include pushing the implant out of the cutting member lumen and into the lumen of the elongate tubular member of the distal portion. The distal portion of the instrument can be positioned adjacent eye tissue to position the implant in the eye, for example, between the ciliary body and the sclera, while the implant remains at least partially inside the lumen of the distal portion of the instrument. The stent105can be deployed from the instrument upon retraction of the introducer tube1380from the implant while maintaining the implant's position relative to the adjacent eye tissue. The methods of implantation and delivery of the stent105are described in more detail below.

Motion of the cutting and deployment components (e.g., one or more of the cutter tube1312, pusher1320, introducer tube1380, and outer tube1318, if present) can be achieved by one or more actuators1315positioned on one or more regions of the handle1305. In some implementations, the one or more actuators1315for a first function of the delivery device1110can be positioned on a first region of the handle1305and one or more actuators1315for a second function of the delivery device1110can be positioned on a second region of the handle1305. A first plurality of actuators1315can be positioned on a first region the handle1305to prepare the patch of material101into a stent and a second plurality of actuators1315can be positioned on a second region of the handle1305to deploy the stent105cut from the patch101. For example, the top region of the handle1305can include a first actuator(s)1315for capturing and/or stretching the patch of material101, a second actuator(s)1315for moving the cutter tube1312to cut the patch of material101, and a third actuator(s)1315for moving the pusher1320to position the cut stent105into a primed position for deployment from the device1110. A bottom region of the handle1305can include a fourth actuator(s)1315for deploying the stent105in the eye.

FIG.13Ashows a top view of an implementation of a delivery device1110andFIG.13Bshows a bottom view of the device1110. The top region of the handle1305can include a first actuator1315that is the stretcher1350for capturing and stretching the patch of material101within the recess and another actuator1315that is the slider for moving the cutter tube1312. The bottom region of the handle1305can include an actuator1315that is the slider for moving the pusher1320to push the stent105from the outer tube1318.

FIG.18Ashows a top view of an implementation of the delivery device1110andFIG.18Bshows a bottom view of the device1110. The top region of the handle1305can include a first actuator1315that is the stretcher1350for capturing and stretching the patch of material101within the recess, a second actuator1315that is the slider for moving the cutter tube1312, and a third actuator1315that is a wheel for incrementally advancing the pusher1320. The bottom region of the handle1305can include a fourth actuator1315that is a spring retraction button for retracting the introducer tube1380to release the stent105from the shaft1310.

The configuration of the actuators1315can vary. For example, the actuators1315can include any of a variety of sliders, dials, buttons, knobs, or other type of actuator.

In an implementation, the one or more actuators1315configured to axially move the one or more components of the device can include a scroll wheel1385(seeFIG.25). The scroll wheel1385may be connected to a pinion gear1387that engages with a corresponding rack gear1389. Rotation of the pinion gear1387may cause the rack gear1389to move axially and advance or retract any of the axially movable components, such as the pusher1320or the cutter tube1312.FIG.25shows the rack gear1389attached to the pusher1320. The scroll wheel1385can provide more an incremental, precise motion of the component. A scroll wheel advancement mechanism is described in U.S. Pat. No. 10,154,924, and is incorporated herein by reference.

In another implementation, the one or more actuators1315configured to axially move the one or more components of the device can include a spring-loaded push button1390. The introducer tube1380can be urged in a distal direction in an extended state relative to the handle1305, which compresses a front spring1392(seeFIG.26). The push button1390can be held by a latch1394in a forward locked position such that the spring1392remains compressed during advancement of the stent105into the target location in the eye. Upon applying a downward force on the push button1390, the latch1394is released allowing the spring1392to push the introducer tube1380a distance proximally thereby retracting the introducer tube1380. Retraction of the introducer tube1380relative to the pusher1320can act to release the implant105in the eye. A spring-loaded retraction mechanism is described in U.S. Pat. No. 9,241,832, and is incorporated herein by reference.

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

Advancement of the cutter tube1312can cut the stent105out from the patch of material resulting in the stent105being positioned within the lumen of the cutter tube1312. The inner diameter of the cutter tube1312can be substantially the same as the inner diameter of the outer introducer tube1380. The pusher1320can be urged distally through the lumen of the cutter tube1312urging the cut stent105within the lumen into the lumen of the introducer tube1380. However, because the cutter tube1312and the introducer tube1380can be substantially the same in their inner dimensions, the cutter tube1312can be urged backwards by the introducer tube1380as the introducer tube1380is urged proximally by the spring. The stent105can be substantially contained within the implantation conduit and advanced line-to-line within the instrument as it is urged distally. Once the stent105is cut from the patch of material, the pathway of implantation for the stent105can include the lumen of the cutter tube1312, the lumen of the introducer tube1380and any other conduit therebetween so that the stent throughout its transport within the implantation conduit avoids having to transfer between “gaps” or “edges” in the implantation conduit. The implantation conduit provides a smooth path for deployment of the stent105through the instrument.

Trephination of tissue and loading of tissue using a delivery device may be performed simultaneously or sequentially. In a preferred implementation, the cutting and injecting are integrated. This allows for tissue cutting/trephining to be performed in/along the path of implantation. The dimensions of the tissue strip are such that manipulating it can be difficult. Thus, by integrating the cutting and implantation, no additional manipulations are necessary. The tissue can be cut and loaded into a tissue delivery pathway without removing or manipulating the tissue outside of the cutting device prior to transfer into an intra-ocular applier. The same device can be used to trephine tissue forming the stent and then inject/implant the stent into the eye enabling a seamless and atraumatic loading of the fine, micro-sized biostent tissue without transit manipulation.

The tissue can be, for example, corneal, scleral or other cartilaginous tissue. A section of tissue is cut using the delivery device and/or cutting device. The tissue is loaded into a tissue delivery pathway that at least partially include the eye without removing the tissue completely from the cutting device prior to transfer into an intra-ocular delivery device. In a situation where a single integrated trephination/injector device is used, that device is used for both trephination of tissue as well as injection and implantation of the tissue into the eye.

In another implementation, there is performed simultaneous or sequential trephination of tissue and insertion of tissue into the eye. A section of tissue is cut and loaded into a tissue delivery pathway. This is performed using a single device that is configured to trephine tissue and configured to load the trephined tissue into an intra-ocular delivery applier for application of the tissue to the eye.

The applier device can also be used as a delivery device and loading platform device or conduit. In such an implantation, the device is configured to contain or otherwise house the tissue prior to implantation. The device permits longitudinal or other directional movement of the tissue for implantation into the eye. The device can be configured for simultaneous or sequential trephination and application loading of the tissue such that, upon completion of a trephination step, the trephined or cut tissue is loaded within a delivery conduit of the applier device. The trephination device can be coupled to the intraocular delivery device by a coupling or other attachment mechanism, which facilitate tissue transfer into the delivery device.

The stent can be harvested by the trephination device from the patient at the time of surgery. The stent can also be formed from a patch of material obtained from a donor or other tissue-engineering source. The patch of material may be pre-cut into a stent shape and pre-loaded within a region of the delivery device. The patch of material may be cut at the time of implantation using a trephination device.

In an implementation, a patch of material101may be manually loaded through the cut-out windows326of the outer tube318with the pusher320in the lumen328of the outer tube318fully retracted in the proximal position. Once the patch of material101is loaded within the delivery device110, the shaft310and the patch of material101may be loaded within a trephination cartridge205. The cover314of the trephination cartridge205can be removed from the base324revealing the recess321of the base324. The shaft310of the delivery device110is positioned within the slots332,334such that the patch of material101is positioned within the recess321therebetween.

The cover314of the trephination cartridge205is replaced onto the base324compressing and/or tensioning the patch of material101within the trephination cartridge205in the closed configuration. The cutting member312can be inserted through the bore338of the cover314urging the blades344through the cover314towards the patch of material101. The cutting member312can be seated within the trephination cartridge205such that the blades344of the cutting member312fully slice through the patch of material101. With the blades344still in the full cut position relative to the trephination cartridge205, the pusher320is urged distally to prime the shaft310and place the now cut stent105within the lumen of the outer tube318towards the opening from the lumen328near the distal-most end of the tube318. The delivery device110is now ready to be used in a patient.

In an implementation, a patch of material101may be loaded within the recess1321of a delivery device1110. The access door1314may be opened and the patch of material101placed in the recess1321. The door1314may be closed thereby capturing and at least partially compressing the patch of material101within the recess1321. The stretcher1350may be actuated to impart a tension on the patch of material101prior to cutting with the cutter tube1312. The cutter tube1312can be actuated to slide distally thereby cutting the patch of material101into a stent105. The pusher1320can then be urged distally to prime the shaft1310by positioning the cut stent105within a distal end region of the lumen1382of the introducer tube1380. The pusher1320, once advanced distal to the rigid outer tube1318, can relax into a curved shape thereby urging the introducer tube1380to also take on this curved shape. The delivery device110is now ready to be used in a patient. The introducer tube1380may be flexible and/or have a curved shaped at its distal end region, as discussed above, configured to conform to a shape of the desired implantation location, such as the curvature of the eye near the anterior angle.

In general, the stent105positioned within the shaft of the delivery device can be implanted through a clear corneal or scleral incision that is formed using the delivery device or a device separate from the delivery device. A viewing lens such as a gonioscopy lens can be positioned adjacent the cornea. The viewing lens enables viewing of internal regions of the eye, such as the scleral spur and scleral junction, from a location in front of the eye. The viewing 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 in visualization. Ultrasonic guidance can be used as well using high-resolution bio-microscopy, OCT, and the like. Alternatively, a small endoscope can be inserted through another limbal incision in the eye to image the eye during implantation.

The distal tip of the shaft holding the stent105can penetrate through the cornea (or sclera) to access the anterior chamber. In this regard, the single incision can be made in the eye, such as within the limbus of the cornea. In an embodiment, the incision is very close to the limbus, such as either at the level of the limbus or within 2 mm of the limbus in the clear cornea. The shaft can be used to make the incision or a separate cutting device can be used. For example, a knife-tipped device or diamond knife can be used initially to enter the cornea. A second device with a spatula tip can then be advanced over the knife tip wherein the plane of the spatula is positioned to coincide with the dissection plane.

The corneal incision can have a size that is sufficient to permit passage of the shaft. In an embodiment, the incision is about 1 mm in size. In another embodiment, the incision is no greater than about 2.85 mm in size. In another embodiment, the incision is no greater than about 2.85 mm and is greater than about 1.5 mm. It has been observed that an incision of up to 2.85 mm is a self-sealing incision.

After insertion through the incision, the shaft can be advanced into the anterior chamber along a pathway that enables the stent105to be delivered from the anterior chamber into the target location, such as the supraciliary or suprachoroidal space. With the shaft positioned for approach, the shaft can be advanced further into the eye such that the distal-most tip of the shaft penetrates the tissue at the angle of the eye, for example, the iris root or a region of the ciliary body or the iris root part of the ciliary body near its tissue border with the scleral spur.

The scleral spur is an anatomic landmark on the wall of the angle of the eye. The scleral spur is above the level of the iris but below the level of the trabecular meshwork. In some eyes, the scleral spur can be masked by the lower band of the pigmented trabecular meshwork and be directly behind it. The shaft can travel along a pathway that is toward the angle of the eye and the scleral spur such that the shaft passes near the scleral spur on the way to the supraciliary space, but does not necessarily penetrate the scleral spur during delivery. Rather, the shaft can abut the scleral spur and move downward to dissect the tissue boundary between the sclera and the ciliary body, the dissection entry point starting just below the scleral spur near the iris root or the iris root portion of the ciliary body. In another embodiment, the delivery pathway of the implant intersects the scleral spur.

The shaft can approach the angle of the eye from the same side of the anterior chamber as the deployment location such that the shaft does not have to be advanced across the iris. Alternately, the shaft can approach the angle of the eye from across the anterior chamber AC such that the shaft is advanced across the iris and/or the anterior chamber toward the opposite angle of the eye. The shaft can approach the angle of the eye along a variety of pathways. The shaft does not necessarily cross over the eye and does not intersect the center axis of the eye. In other words, the corneal incision and the location where the stent105is implanted at the angle of the eye can be in the same quadrant when viewed looking toward the eye along the optical axis. Also, the pathway of the stent105from the corneal incision to the angle of the eye ought not to pass through the centerline of the eye to avoid interfering with the pupil.

The shaft can be continuously advanced into the eye, for example approximately 6 mm. The dissection plane of the shaft can follow the curve of the inner scleral wall such that the stent105mounted in the shaft, for example after penetrating the iris root or the iris root portion of the ciliary body CB, can bluntly dissect the boundary between tissue layers of the scleral spur and the ciliary body CB such that a distal region of the stent105extends through the supraciliary space and then, further on, is positioned between the tissue boundaries of the sclera and the choroid forming the suprachoroidal space.

Once properly positioned, the stent105can be released. In some implementations, the stent105can be released by withdrawing the outer tube318of the shaft310while the pusher320prevents the stent105from withdrawing with the outer tube318. In other implementations, the stent105can be released by withdrawing the introducer tube1380while the pusher1320remains stationary, as described elsewhere herein.

Once implanted, the stent105forms a fluid communication pathway between the anterior chamber and the target pathway (e.g., supraciliary space or suprachoroidal space). As mentioned, the stent105is not limited to being implanted into the suprachoroidal or supraciliary space. The stent105can be implanted in other locations that provide fluid communication between the anterior chamber and locations in the eye, such as Schlemm's canal or a subconjunctival location of the eye. In another implementation, the stent105is implanted to form a fluid communication pathway between the anterior chamber and the Schlemm's canal and/or communication pathway between the anterior chamber and a subconjunctival location of the eye. It should be appreciated the device described herein can also be used to deliver a stent trans-sclerally as well from an ab interno approach.

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

A wide variety of systemic and ocular conditions such as inflammation, infection, cancerous growth, may be prevented or treated using the stents described herein. More specifically, ocular conditions such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, herpes simplex viral and adenoviral infections can be treated or prevented.

The following classes of drugs could be delivered using the devices of the present invention: antiproliferatives, antifibrotics, anesthetics, analgesics, cell transport/mobility impending agents such as colchicine, vincristine, cytochalasin B and related compounds; antiglaucoma drugs including beta-blockers such as timolol, betaxolol, atenolol, and prostaglandin analogues such as bimatoprost, travoprost, latanoprost etc; carbonic anhydrase inhibitors such as acetazolamide, methazolamide, dichlorphenamide, diamox; and neuroprotectants such as nimodipine and related compounds. Additional examples include antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamycin, and erythromycin; antibacterials such as sulfonamides, sulfacetamide, sulfamethizole and sulfisoxazole; anti-fungal agents such as fluconazole, nitrofurazone, amphotericine B, ketoconazole, and related compounds; anti-viral agents such as trifluorothymidine, acyclovir, ganciclovir, DDI, AZT, foscamet, vidarabine, trifluorouridine, idoxuridine, ribavirin, protease inhibitors and anti-cytomegalovirus agents; antiallergenics such as methapyriline; chlorpheniramine, pyrilamine and prophenpyridamine; anti-inflammatories such as hydrocortisone, dexamethasone, fluocinolone, prednisone, prednisolone, methylprednisolone, fluorometholone, betamethasone and triamcinolone; decongestants such as phenylephrine, naphazoline, and tetrahydrazoline; miotics and anti-cholinesterases such as pilocarpine, carbachol, di-isopropyl fluorophosphate, phospholine iodine, and demecarium bromide; mydriatics such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine; sympathomimetics such as epinephrine and vasoconstrictors and vasodilators; Ranibizumab, Bevacizamab, and Triamcinolone.

Non-steroidal anti-inflammatories (NSAIDs) may also be delivered, such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, for example ASPIRIN® from Bayer AG, Leverkusen, Germany; ibuprofen, for example ADVIL® from Wyeth, Collegeville, Pa.; indomethacin; mefenamic acid), COX-2 inhibitors (CELEBREX® from Pharmacia Corp., Peapack, N.J.; COX-1 inhibitors), including a prodrug Nepafenac®; immunosuppressive agents, for example Sirolimus (RAPAMUNE®, from Wyeth, Collegeville, Pa.), or matrix metalloproteinase (MMP) inhibitors (e.g., tetracycline and tetracycline derivatives) that act early within the pathways of an inflammatory response. Anticlotting agents such as heparin, antifibrinogen, fibrinolysin, anti clotting activase, etc., can also be delivered.

Antidiabetic agents that may be delivered using the present devices include acetohexamide, chlorpropamide, glipizide, glyburide, tolazamide, tolbutamide, insulin, aldose reductase inhibitors, etc. Some examples of anti-cancer agents include 5-fluorouracil, adriamycin, asparaginase, azacitidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, estramustine, etoposide, etretinate, filgrastin, floxuridine, fludarabine, fluorouracil, fluoxymesterone, flutamide, goserelin, hydroxyurea, ifosfamide, leuprolide, levamisole, lomustine, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, pentostatin, pipobroman, plicamycin, procarbazine, sargramostin, streptozocin, tamoxifen, taxol, teniposide, thioguanine, uracil mustard, vinblastine, vincristine and vindesine.

Hormones, peptides, nucleic acids, saccharides, lipids, glycolipids, glycoproteins, and other macromolecules can be delivered using the present devices. Examples include: endocrine hormones such as pituitary, insulin, insulin-related growth factor, thyroid, growth hormones; heat shock proteins; immunological response modifiers such as muramyl dipeptide, cyclosporins, interferons (including α, β, and γ interferons), interleukin-2, cytokines, FK506 (an epoxy-pyrido-oxaazcyclotricosine-tetrone, also known as Tacrolimus), tumor necrosis factor, pentostatin, thymopentin, transforming factor beta2, erythropoetin; antineogenesis proteins (e.g., anit VEGF, Interfurons), among others and anticlotting agents including anticlotting activase. Further examples of macromolecules that can be delivered include monoclonal antibodies, brain nerve growth factor (BNGF), celiary nerve growth factor (CNGF), vascular endothelial growth factor (VEGF), and monoclonal antibodies directed against such growth factors. Additional examples of immunomodulators include tumor necrosis factor inhibitors such as thalidomide.

In various implementations, description is made with reference to the figures. However, certain implementations may be practiced without one or more of these specific details, or in combination with other known methods and configurations. In the description, numerous specific details are set forth, such as specific configurations, dimensions, and processes, in order to provide a thorough understanding of the implementations. In other instances, well-known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the description. Reference throughout this specification to “one embodiment,” “an embodiment,” “one implementation, “an implementation,” or the like, means that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment or implementation. Thus, the appearance of the phrase “one embodiment,” “an embodiment,” “one implementation, “an implementation,” or the like, in various places throughout this specification are not necessarily referring to the same embodiment or implementation. Furthermore, the particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more implementations.

The use of relative terms throughout the description may denote a relative position or direction. For example, “distal” may indicate a first direction away from a reference point. Similarly, “proximal” may indicate a location in a second direction opposite to the first direction. The reference point used herein may be the operator such that the terms “proximal” and “distal” are in reference to an operator using the device. A region of the device that is closer to an operator may be described herein as “proximal” and a region of the device that is further away from an operator may be described herein as “distal”. Similarly, the terms “proximal” and “distal” may also be used herein to refer to anatomical locations of a patient from the perspective of an operator or from the perspective of an entry point or along a path of insertion from the entry point of the system. As such, a location that is proximal may mean a location in the patient that is closer to an entry point of the device along a path of insertion towards a target and a location that is distal may mean a location in a patient that is further away from an entry point of the device along a path of insertion towards the target location. However, such terms are provided to establish relative frames of reference, and are not intended to limit the use or orientation of the devices to a specific configuration described in the various implementations.

While this specification contains many specifics, these should not be construed as limitations on the scope of what is claimed or of what may be claimed, but rather as descriptions of features specific to particular embodiments. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or a variation of a sub-combination. Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Only a few examples and implementations are disclosed. Variations, modifications and enhancements to the described examples and implementations and other implementations may be made based on what is disclosed.

In the descriptions above and in the claims, phrases such as “at least one of” or “one or more of” may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including 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” are each intended to 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.”

Use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible.

The systems disclosed herein may be packaged together in a single package. The finished package would be sterilized using sterilization methods such as Ethylene oxide or radiation and labeled and boxed. Instructions for use may also be provided in-box or through an internet link printed on the label.