HK40057933B - Ocular delivery systems and methods - Google Patents

Description

Eye delivery system and method

This application is a divisional application of the invention patent application filed on March 31, 2015, with application number 201580079974.6 and entitled "Eye Delivery System and Method".

Technical Field

This document describes Schlemm's canal for access into the eye and systems and methods for delivering ocular devices, tools, or fluid compositions therein. The ocular device can keep the Schlemm's canal open without substantially interfering with aqueous humor fluid flowing through the canal via its walls, lumen, circumferentially, or longitudinally. Delivery tools can be used to rupture the trabecular meshwork. Fluid compositions can be viscoelastic fluids delivered into the canal or aqueous humor collection tube to facilitate the drainage of aqueous humor by expanding the canal, rupturing the walls of the proximal tubules and adjacent walls of the Schlemm's canal, and/or increasing aqueous humor permeability through the trabecular tubules, or via a transmural outflow path. Minimally invasive methods for treating medical conditions associated with elevated intraocular pressure, including glaucoma, are also described.

Background Technology

Glaucoma is a potentially blinding disease affecting more than 60 million people worldwide, or about 1% to 2% of the population. Glaucoma is typically characterized by elevated intraocular pressure. This increased pressure in the eye can cause irreversible damage to the optic nerve, which, if left untreated, can lead to vision loss and even blindness. A consistent reduction in intraocular pressure may slow or stop the progressive vision loss associated with glaucoma.

Increased intraocular pressure is usually caused by the suboptimal outflow or drainage of fluid (aqueous humor) from the eye. Aqueous humor, or aqueous humor, is a clear, colorless fluid that continuously replenishes the eye. It is produced by the ciliary body and subsequently exits the eye primarily through the trabecular meshwork. The trabecular meshwork extends around the circumference of the eye at the anterior chamber angle or drainage angle, forming at the intersection between the peripheral iris or iris root, the anterior sclera or scleral spur, and the peripheral cornea. The trabecular meshwork feeds outward into the Schlemm's canal, a narrow circumferential passage that typically surrounds the outer boundary of the meshwork. Positioned around and extending radially from the Schlemm's canal are the aqueous humor veins or collecting ducts that receive the draining fluid. Net outflow or drainage of aqueous humor can be reduced as a result of decreased outflow patency, reduced outflow through the trabecular meshwork and the Schlemm's drainage system, increased pressure in the suprascleral veins, or, possibly, increased aqueous humor production. The flow out of the eye can also be restricted by blockage or constriction of the trabecular meshwork and/or the Schlemm's canal and its collecting ducts.

Currently, glaucoma, early-stage glaucoma, and ocular hypertension can be treated by lowering intraocular pressure using one or more modalities, including medication, surgical resection, laser surgery, cryotherapy, and other surgical procedures. Generally, medication or drug therapy is the first-line treatment. If medication is not effective enough, more invasive surgical treatments can be used. For example, the standard surgical resection procedure for lowering intraocular pressure is trabeculectomy or filtration surgery. This procedure involves creating a new drainage site for the aqueous humor. A new drainage path is created by removing a portion of the sclera and trabecular meshwork at the drainage angle, instead of allowing the aqueous humor to drain naturally through the trabecular meshwork. This creates an opening or pathway between the anterior chamber and the subconjunctival space, through which the aqueous humor drains via conjunctival vessels and lymphatic vessels. The new opening may be covered by the sclera and/or conjunctiva to create a new reservoir called a vesicle into which the aqueous humor drains. However, the traditional trabeculectomy procedure carries both short-term and long-term risks. These risks include: blockage of surgically created openings through scar formation or other mechanisms, low intraocular pressure or abnormally low intraocular pressure, expulsion hemorrhage, anterior chamber hemorrhage, intraocular infection or endophthalmitis, shallow anterior chamber angle, macular hypotension, choroidal exudation, suprachoroidal hemorrhage, etc.

An alternative is to implant a device into the Schlem canal that keeps the canal open or facilitates the flow of aqueous humor from the anterior chamber into the canal. Various vascular stents, shunts, catheters, and procedures have been designed for this purpose, with implants or catheters delivered to the Schlem canal via an external approach (from outside the eye). This placement method is invasive and often lengthy, requiring the creation of a tissue flap and a deep incision to access the canal. Furthermore, locating and accessing the Schlem canal via this external approach is very difficult for many surgeons because the Schlem canal has a small diameter, for example, a cross-sectional diameter of approximately 50 to 250 micrometers, and may be even smaller when constricted. One such procedure, external canal reshaping, involves creating a deep scleral incision and flap; locating and decapitating the Schlem canal; encircling the canal 360 degrees from outside the eye with a catheter; and using viscoelastic, circumferentially tightened sutures, or both, to help keep the canal open. The procedure is quite challenging and can take anywhere from forty-five minutes to two hours. The long-term safety and efficacy of tubule reshaping are very promising, but the procedure remains challenging and invasive in terms of surgical procedures.

Another alternative is viscoelastic canaliculiotomy, which involves injecting a viscoelastic solution into the Schlem canal to expand the canal and its associated collection canal. This expansion of the canal and collection canal generally facilitates the drainage of aqueous humor from the anterior chamber through the trabecular meshwork and Schlem canal, and out through the natural trabecular canaliculus outflow pathway. Viscoelastic canaliculiotomy is similar to canaliculoplasty (both are invasive and external), except that viscoelastic canaliculiotomy does not involve sutures and does not restore the full 360-degree outflow facility. Some advantages of viscoelastic canaliculiotomy include the avoidance of sudden drops in intraocular pressure, anterior chamber hemorrhage, hypotony, and a flattened anterior chamber. The risk of cataract formation and infection is also reduced due to the loss of complete intraocular manipulation and intact eyewall penetration, shallowing of the anterior chamber opening, and minimized iridectomy. Another advantage of viscoelastic canaliculiotomy is that the procedure restores most of the eye's physiological outflow pathway, thus avoiding the need for external filtration and its associated short- and long-term risks. This makes the success of the surgery partially independent of conjunctival or scleral scarring, a major cause of failure in conventional trabeculectomy procedures. Furthermore, the absence of elevated filtering blebs avoids associated ocular discomfort and potential damaging ocular infections, and the surgery can be performed in any quadrant of the outflow pathway.

However, current viscoelastic canaliculus incision and canaliculus reshaping techniques remain highly invasive because access to the Schlem's canal requires creating a deep incision in the sclera, generating a scleral flap, and detopping the Schlem's canal. In their current form, these procedures are two “external” approaches. “External” generally means “from the outside” and is inherently more invasive given the location of the Schlem's canal and the amount of tissue rupture required for external access. On the other hand, “internal” means “from the inside” and is a less invasive approach due to the reduced amount of tissue rupture required for internal access. Therefore, the internal approach for the Schlem's canal provides surgeons with easier access to the canal and reduces the risk to the patient's eye and morbidity. All of these contribute to improved patient recovery and rehabilitation. External viscoelastic canaliculus incision and canaliculus reshaping procedures remain challenging for surgeons because, as previously stated, due to the small diameter of the Schlem's canal, it is difficult to locate and access it from the outside using deep incisions. Another major drawback is that viscoelastic tubule incision typically expands up to 60 degrees to the Schlem tube, which is a 360-degree annular outflow container structure. The more the tube can expand, the greater the total amount of aqueous humor outflow that can be restored.

Therefore, a system that provides easy and non-invasive access to the canal using an internal approach for delivering ocular devices, tools, and compositions would be beneficial. A system that efficiently delivers devices, tools, and compositions into the Schlem canal to reduce surgical time and infection risk without compromising the safety and accuracy of the delivery process would also be useful. A system that delivers devices, tools, and fluid compositions into the Schlem canal using an internal approach, allowing cataract and glaucoma surgeries to be performed using virtually identical corneal or scleral incisions during the same surgical setup, would also be useful. This smaller incision allows for less invasive surgery and faster patient recovery. This approach allows access to the Schlem canal from inside the eye through the trabecular mesh, hence the term "internal approach." Methods of delivering eye devices, tools, and compositions that effectively rupture the adjacent walls of the near-small tubing network and Schlem tube (also known as the inner wall of the Schlem tube), keep the Schlem tube open, increase outflow, reduce outflow resistance, or use the system to effectively dilate the tube and/or its collection tube in a minimally invasive, internal manner would also be desirable.

Summary of the Invention

This document describes systems and methods for easily and reliably accessing the Schlemm's canal with minimal or no trauma and for delivering ocular devices (e.g., implants) within the Schlemm's canal. Other systems and methods may be implant-free and/or rely on the delivery and removal of therapeutic (destructive) tools and/or the delivery of fluid compositions into the Schlemm's canal to improve flow through a trabecular tubule outflow system consisting of a trabecular meshwork, proximal tubular tissue: the Schlemm's canal, and a collecting canal. When an ocular device is implanted, the device can keep the Schlemm's canal open without substantially interfering with transmural fluid flow through the canal. Transmural flow, or transmural aqueous humor flow, is defined as the flow of aqueous humor through the trabecular meshwork from the anterior chamber into the lumen of the Schlemm's canal, through and along the lumen of the Schlemm's canal, and ultimately into an aqueous humor collecting canal originating from the outer wall of the Schlemm's canal. When a fluid composition is delivered into the tube, the fluid composition delivered into the tube (e.g., a viscoelastic fluid) can facilitate the drainage of aqueous humor by dilating the tube, making the inner walls of the trabecular meshwork and Schlemm's canals more permeable to aqueous humor, and by dilating the aqueous humor collecting duct. When a therapeutic instrument is delivered, the instrument can promote the drainage of aqueous humor by: dilating the tube; dilating the collecting duct; rupturing or stretching the trabecular meshwork or the proximal tubules; tearing or cutting the trabecular meshwork or the proximal tubules; or completely removing the trabecular meshwork or the proximal tubules. Any or all of these actions can reduce resistance to outflow, increase aqueous humor outflow and drainage, and lower intraocular pressure.

One advantageous feature of the system may be a cannula configured with a distally curved portion having a defined radius of curvature, wherein the radius of curvature directly engages the bevel at the distal tip of the cannula. However, in some variations, the system may include a straight cannula. Specific configurations of the system's handle may also be applicable. The handle may be sized and shaped to facilitate single-handed manipulation. Furthermore, the handle may be designed for universal manipulation. "Universal" means that the handle is ergonomically configured for both right-handed and left-handed use, suitable for any quadrant of the eye, and suitable for inserting the cannula or elongated component into the Schlemm canal in either clockwise or counterclockwise manner. This configuration may include a drive assembly that is easily actuated in a first orientation (e.g., clockwise delivery of implants, tools, and/or fluids) and easily actuated in a second reversible orientation (e.g., counterclockwise delivery of implants, tools, and/or fluids). This configuration may allow actuation of the drive assembly using either the left or right hand, and may allow the drive assembly to be used for either the left or right eye. Alternatively, in some variations, the cannula itself can be rotated to the desired extent (e.g., 180 degrees) to provide ambidextrous ease of use in either clockwise or counterclockwise directions of travel.

The eye delivery system described herein typically comprises a universal handle with a gripping portion and a housing having an inner and a distal end. A cannula is typically attached to and extends distally from the housing. The cannula may include proximal and distal curved portions, wherein the distal curved portion has a proximal end and a distal end, and a radius of curvature defined between the ends. The cannula may also be configured to include: a body; a distal tip having a bevel; and an inner cavity extending from the proximal end through the distal tip. The bevel may directly engage the distal end of the curved portion of the cannula (i.e., the bevel may directly engage the radius of curvature). The system may also typically include a drive assembly substantially contained within the housing, the drive assembly comprising gears that convert rotational movement into linear movement.

When the eye device is to be implanted into the Schlem canal, the system may further include a slidable positioning element having a proximal and distal end, coaxially disposed within the canal lumen. The distal end of the slidable positioning element may include an engagement mechanism for positioning (including manipulating) the eye device within the canal. Exemplary engagement mechanisms that may be employed include hooks, jaws, latches, tweezers, or complementary engaging elements for releasable attachment of the eye device.

The system can be configured to include a fluid assembly in a handle and an elongated component comprising an inner lumen coaxially disposed within the cannula lumen when the fluid composition is to be delivered into the Schlem tube. The fluid composition can be delivered through a distal end of the inner lumen of the elongated component or through openings spaced apart along the axial length of the elongated component. Additionally, the fluid assembly can be connected to a loading assembly configured to transfer the fluid composition into a reservoir at least partially defined by the assembly. Some variations of the system may have a fluid composition pre-loaded into the reservoir. Exemplary fluid compositions include, but are not limited to, saline, pharmaceutical compounds, and viscoelastic fluids. Viscoelastic fluids may include hyaluronic acid, chondroitin sulfate, cellulose, or salts, derivatives, or mixtures thereof. Using sodium hyaluronate as a viscoelastic fluid may be advantageous. Some systems can be configured to deliver a therapeutic (destructive) tool into the Schlem tube without delivering an implant or fluid. In these variations, the handle may or may not include a reservoir, and the tool may have various configurations for causing tissue rupture. An exemplary system may include an elongated component comprising a non-invasive distal tip configured to advance through the Schlem tube and configured to cause the body of the elongated component to tear or cut through the trabecular mesh when the system is removed from the eye.

A method for implanting an ocular device within a Schlemm canal is also described. Using the ocular delivery system disclosed herein, the method typically includes the following steps: creating an incision in the ocular wall providing access to the anterior chamber of the eye; advancing a cannula of the system through the incision, passing through a portion of the anterior chamber to reach the trabecular meshwork; and piercing the trabecular meshwork; inserting the cannula into the Schlemm canal; and implanting the device into the canal. The cannula typically includes: proximal and distal curved portions, the distal curved portion having a proximal end and a radius of curvature defined between the ends; a body; a distal tip with a bevel that directly engages the distal end of the curved portion of the cannula; and an inner lumen extending from the proximal end through the distal tip. A positioning element that can slide within the lumen of the cannula may be used during the step of implanting the device into the canal. The device may be implanted to lower intraocular pressure or treat medical conditions such as glaucoma, early glaucoma, or high intraocular pressure.

A method for delivering a fluid composition into a Schlemm tube is further described. Using the ocular delivery system disclosed herein, the method typically includes the steps of: creating an incision in the ocular wall providing access to the anterior chamber of the eye; advancing a cannula of the system through the incision into the trabecular meshwork; inserting the cannula into the Schlemm tube; and delivering the fluid composition into the Schlemm tube using an elongated member comprising a lumen that slides within the lumen of the cannula. The cannula typically includes: proximal and distal curved portions having a proximal end and a distal end and a radius of curvature defined between the ends; a body; a distal tip having a bevel that directly engages the distal end of the curved portion of the cannula; and a lumen extending from the proximal end through the distal tip. The fluid composition can be delivered into the Schlemm tube through the distal end of the elongated member or through openings spaced apart along the axial length of the elongated member. For example, fluids such as saline and viscoelastic solutions can be delivered into the tubes to expand the tubes and collecting tubes and/or rupture the inner walls of the proximal tubules or Schlemm tubes, thereby increasing the permeability of aqueous humor, reducing resistance to outflow, or increasing outflow. Examples of viscoelastic solutions include those containing hyaluronic acid, chondroitin sulfate, cellulose, and their derivatives and mixtures. As previously stated, using sodium hyaluronate as a viscoelastic solution can be advantageous. Medications for treating glaucoma, steroids, anti-angiogenic agents (e.g., anti-vascular endothelial growth factor (anti-VEGF) antibodies and derivatives), anti-inflammatory agents, or anti-fibrotic agents can also be combined with viscoelastic solutions. If necessary, only the medication can be delivered without a viscoelastic agent.

When delivering the fluid composition, the delivery step may include actuating a drive assembly such that at least a portion of the gear contracts (or reverses the movement of the gear) to a sufficient amount to pressurize the reservoir by causing the fluid composition to pass through the cavity of the elongated member. The fluid composition may be delivered to expand the Schlemm tube. The fluid composition may also be delivered to lower intraocular pressure or to treat medical conditions such as glaucoma.

The systems, apparatus, and methods described herein can also employ varying degrees of force to rupture trabecular tubule tissues (e.g., trabecular meshwork, proximal tubule tissue, Schlem's canal, the wall of Schlem's canal, collagen septa, obstruction, or narrowed portion within Schlem's canal, and collecting canal), thereby improving aqueous humor drainage and subsequently reducing intraocular pressure and treating the ocular condition. The destructive force can be generated by non-implantable methods, such as by delivering a destructive volume of viscoelastic fluid that can expand the tubes and collecting canal and also stretch the trabecular meshwork; advancing a destructive tool (e.g., cannula, tubing, catheter, enlarging probe, balloon, etc.), which may or may not include one or more destructive components on its distal portion; or both. Depending on factors such as the type or severity of the condition being treated, destructive forces can be generated to partially cut, tear, stretch, expand, destroy, or completely destroy and/or remove the trabecular meshwork and/or proximal tubular tissue, and can be adjusted by changing the volume of the delivered viscoelastic fluid or by changing the tool configuration, as further discussed below.

Viscoelastic fluids or aqueous humor can be delivered using integrated and single-handed, single-operator control systems. Advancement of destructive tools can also be provided via integrated and single-handed, single-operator control systems. "Integrated" means using a single system to advance elongated components through at least a portion of the Schlem tube, and in some cases, also to deliver viscoelastic fluids, tools, or implants into the Schlem tube. "Single-operator control" means that all features of the system (e.g., cannula, elongated components, and tool advance and retraction, ocular device delivery, fluid delivery, etc.) can be performed by a single user. This contrasts with other systems that use forceps to insert delivery catheters into the Schlem tube and/or separate or catheter-independent devices containing viscoelastic fluid, which require connection to the delivery catheter by one or more assistants during surgery, while the delivery catheter is held by the surgeon. Subsequent delivery of destructive volumes of fluid or tools, implants (e.g., helical supports or structures) can be introduced into the Schlem tube to keep it open, or energy can be delivered to modify the structure of the Schlem tube and/or surrounding trabecular tubules.

A one-handed, single-operator control system for delivering fluid may include: a cannula; an elongated member including an inner cavity and slidably disposed within the cannula and advanceable from a distal end of the cannula; and a handle connected to the cannula, wherein a portion of the handle defines a reservoir, and wherein the handle is operable with one hand to deliver fluid from the reservoir through the inner cavity of the elongated member.

Alternatively, a system for delivering viscoelastic fluid may include: a cannula; an elongated member including an inner cavity and slidably disposed within the cannula and advanceable from a distal end of the cannula; a handle connected to the cannula, wherein a portion of the handle defines a reservoir; and a linear gear movable to advance fluid from the reservoir through the inner cavity of the elongated member.

Systems for delivering viscoelastic fluids can also be configured to include: a universal handle having a proximal and a distal end; a sleeve extending from the distal end and having a proximal and a distal portion; a slidable elongated member including an inner cavity and disposed within the sleeve; a housing having an inner, upper, and lower surface; and a pulley drive assembly; wherein the pulley drive assembly extends beyond the upper and lower surfaces of the housing. Such a system with a universal handle may further include a rotatable (e.g., rotated from a left to a right) rotating sleeve and pulley drive assembly, the pulley drive assembly including a single roller (rotatable component) configured to slide the elongated member. Instead of a roller, a button, a slide, a foot pedal, or a motorized mechanism may also be configured to slide the elongated member.

In all variations of viscoelastic fluid delivery systems, the elongated component may include an inner cavity and may have an outer diameter ranging from about 25 micrometers to about 1000 micrometers, about 25 micrometers to about 500 micrometers, about 50 micrometers to about 500 micrometers, about 150 micrometers to about 500 micrometers, about 200 micrometers to about 500 micrometers, about 300 micrometers to about 500 micrometers, about 200 micrometers to about 250 micrometers, or about 180 micrometers to about 300 micrometers. In some examples, an outer diameter of about 240 micrometers may be advantageous for the elongated component. The elongated component may also include a plurality of openings spaced apart along at least a portion of its axial length and have a distal end with a cut configured as a half-tube.

In addition to using a destructive volume of viscoelastic fluid to rupture the Schlem's canal and surrounding trabecular meshwork, the outer diameter of the elongated component can be sized to rupture those tissues. For example, an elongated component with an outer diameter in the range of about 200 micrometers to about 500 micrometers may be advantageous for rupturing tissue. Furthermore, the distal portion of the elongated component may contain destructive components for rupturing tissue, such as notches, hooks, barbs, bladders, or combinations thereof. However, the system may not necessarily include both features: delivery of a destructive volume of viscoelastic fluid and an elongated component sized for rupture. An elongated component configured to rupture the Schlem's canal and surrounding tissue may serve only to reduce intraocular pressure without delivering fluid. Such an elongated component may or may not have an inner lumen. In some variations, the elongated component may be configured to cause the body of the elongated component to cut or tear the trabecular meshwork when the system is removed from the eye. The elongated component may also be configured to include a bladder or otherwise inflate or expand to a size sufficient to rupture tissue as it advances.

The handle of the viscoelastic fluid delivery system described herein may include a drive assembly capable of delivering fluid from a reservoir through the interior of an elongated member. The drive assembly may be a pulley drive assembly including one or more rotatable components. The reservoir may be pre-loaded with a viscoelastic fluid. Exemplary viscoelastic fluids may include hyaluronic acid, chondroitin sulfate, cellulose, polymers, or salts, derivatives, or mixtures thereof. Using sodium hyaluronate as a viscoelastic fluid may be advantageous.

In some variations, the system described herein for introducing a fluid composition into a Schlemm tube may include a housing, a sleeve, a resilient elongated member, a reservoir, and a drive assembly. The sleeve may be attached to a distal end of the housing and may include a distal tip. The resilient elongated member may include an inner lumen and a distal end, the distal end being slidable within the sleeve between a retracted position and an extended position. The distal end may be within the sleeve in the retracted position and distal to the distal tip of the sleeve in the extended position. The reservoir may include the fluid composition and may be fluidly connected to the inner lumen of the resilient elongated member. The drive assembly may be configured to simultaneously move the resilient elongated member from the extended position to the retracted position and deliver the fluid composition from the reservoir through the inner lumen of the resilient elongated member. In some variations, the system may further include a lock configurable to prevent movement of the reservoir relative to the housing. In some examples, the system may be configured to prevent movement of the resilient polymer elongated member toward the extended position after the resilient elongated member has retracted a fixed cumulative distance. In some of these examples, the fixed cumulative distance may be approximately 40 mm.

In some examples, the drive assembly may include a linear gear. Translation of the linear gear in a first direction may move the resilient elongated member toward a retracted configuration and deliver a fluid composition from a reservoir through the cavity of the elongated member. In some of these examples, translation of the linear gear in a second direction may move the resilient elongated member toward an extended configuration. The volume of fluid composition delivered from the reservoir may correspond to the distance the resilient polymer elongated member moves toward the extended configuration. In some variations, the drive assembly may further include a rotatable component, and rotation of the rotatable component may cause translation of the linear gear. In some examples, the volume of fluid composition delivered from the reservoir may correspond to the distance the linear gear translates along the first direction.

A device for introducing a fluid composition into a Schlemm tube is also described herein. The device may include a housing, a reservoir, an elongated, resilient polymer member, and a drive assembly. The reservoir may hold the fluid composition and may be positioned within the housing. The elongated, resilient polymer member may include an inner cavity fluidly connected to the reservoir. The drive assembly may be configured such that a volume of the fluid composition is delivered from the reservoir into the Schlemm tube via the inner cavity of the elongated, resilient polymer member, and such that the elongated, resilient polymer member is translated a certain distance relative to the housing. The volume of the delivered fluid composition and the distance translated relative to the elongated, resilient polymer member are fixed. In some variations, the drive assembly may include a rotatable roller, and the volume of the delivered fluid composition and the distance translated by the elongated, resilient polymer member, relative to the amount of rotation of the roller may be fixed.

Implant-free methods for treating eye conditions may include inserting an elongated component into the Schlem canal, wherein the elongated component is already loaded with a volume of viscoelastic fluid, and a volume of viscoelastic fluid sufficient to rupture the trabecular tubules to reduce intraocular pressure is delivered into the Schlem canal. However, implant-free methods for treating eye conditions may not necessarily include the delivery of viscoelastic fluid. In these examples, the method may include inserting an elongated component into the Schlem canal, wherein the elongated component has a diameter between about 200 micrometers and about 500 micrometers, and wherein the advancement, contraction, or removal of the elongated component in the Schlem canal ruptures the trabecular tubules sufficient to reduce intraocular pressure. In some examples, the method may include a system for removing the component from the eye, thereby cutting or tearing the trabecular meshwork with the body of the elongated component.

Other methods for treating eye conditions may include a one-handed, single-operator method for introducing viscoelastic fluid into a Schlem tube, the method comprising: inserting an elongated member into the Schlem tube, wherein the elongated member is already loaded with a volume of viscoelastic fluid; and delivering the viscoelastic fluid into the Schlem tube, wherein the delivery of the volume of viscoelastic fluid is achieved by a one-handed system used by a single operator.

When the viscoelastic fluid is delivered using the methods disclosed herein, the destructive volume can be between about 2 μl (µL) and about 16 μl (µL), or between about 2 μl and about 8 μl. In some variations of the method, the fluid volume capable of rupturing trabecular tubule tissue is about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl, about 11 μl, about 12 μl, 13 μl, about 14 μl, about 15 μl, or about 16 μl. In some examples, delivering a volume of about 4 μl of viscoelastic fluid can be advantageous. In yet other variations, the delivered fluid volume ranges from about 1 μl per 360 degrees of the tube to about 50 μl per 360 degrees of the tube. In other variations, the delivered fluid volume ranges from approximately 0.5 μl per 360 degrees of the tube to approximately 500 μl per 360 degrees. The viscoelastic fluid can be delivered to simultaneously advance an elongated component of a single-handed, single-operator controlled system in a clockwise, counterclockwise, or both direction, and/or during removal of the elongated component from the Schlem tube. The delivered viscoelastic fluid volume can be fixed relative to the distance traveled by the elongated component, and the viscoelastic fluid can be delivered around the Schlem tube a distance equal to the distance the elongated component travels around the tube. As previously stated, the viscoelastic fluid can be delivered to cause rupture of the Schlem tube and surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid can induce rupture by: dilating the Schlem tube; increasing the porosity of the trabecular network; stretching the trabecular network; forming microfractures or perforations in the proximal tubular tissue; removing collagen septa from the Schlem tube; dilating the collection tube, or combinations thereof. At the start of an eye surgery, a slender component may be loaded with viscoelastic fluid, allowing a single operator to manipulate the system (e.g., advance and retract the slender component or any associated tool) with one hand and deliver the fluid into the trabecular tubule tissue.

The methods disclosed herein may also include advancing the elongated component into the Schlem tube by approximately 360 degrees of arc, 180 degrees of arc, 90 degrees of arc, or other angular arcs (e.g., between approximately 5 degrees of arc and approximately 360 degrees of arc). Advancement may occur from a single point of entry or from multiple points of entry within the Schlem tube. The disclosed methods can also be used to treat various ocular conditions, including (but not limited to) glaucoma, early-stage glaucoma, and high intraocular pressure.

Methods for internal trabeculotomy and goniotomy are also disclosed using the systems and steps disclosed herein, the methods comprising: inserting a cannula at least partially into the anterior chamber of the eye; inserting the Schlem canal at a single entry point using the cannula; and delivering a volume of viscoelastic fluid into the lumen of an elongated member that is slidable within the cannula and expandable with respect to the cannula, thereby causing structural rupture of the Schlem canal and surrounding trabecular tubules to reduce intraocular pressure. Another method for treating ocular conditions comprises: inserting an elongated member that is expandable from a single operator-controlled handle into the Schlem canal, the handle including a reservoir; and delivering a volume of viscoelastic fluid from the reservoir to the lumen of the elongated member by increasing the pressure within the reservoir, wherein the delivered volume of viscoelastic fluid is sufficient to cause structural rupture of the Schlem canal and surrounding tissues to reduce intraocular pressure. Other methods for internal trabeculotomy and goniotomy may involve cutting, tearing, and/or removing the trabecular meshwork without delivering viscoelastic fluid. In this method, an elongated component configured to mechanically tear or cut and remove the trabecular meshwork can be used. In some methods, the elongated component is configured to mechanically tear or cut the trabecular meshwork when removed from the eye delivery system after the elongated component has been inserted into the Schlem tube. In other methods, the elongated component may include a tool with a larger diameter, cutting features, and/or along or located on the distal portion of the elongated component. For example, if the trabecular meshwork is both cut and removed, the tube can pull the excised tissue back into the sleeve during contraction.

The methods described herein for treating eye conditions may include inserting an elongated member into a Schlemm tube and retracting the elongated member. The elongated member may include an inner lumen having a distal opening at its distal tip, and retracting the elongated member may include simultaneously delivering a fluid composition outside the distal opening of the inner lumen. In some variations, both retracting the elongated member and delivering the fluid composition may be actuated by rotation of a roller. In some examples, the elongated member may advance a first length around the Schlemm tube, and the fluid composition may be delivered around the Schlemm tube for the same first length. In some of the methods described herein, the elongated member may be rotated approximately 180 degrees around the Schlemm tube in a first direction. Some of these methods may further include advancing the elongated member approximately 180 degrees around the Schlemm tube in a second direction and retracting the elongated member while simultaneously delivering the fluid composition outside the distal opening of the inner lumen.

In some variations, the method described herein for delivering a fluid composition into a Schlemm tube using an apparatus may include moving the proximal end of a plunger from an extended position to a depressed position within the reservoir, such that the plunger displaces the fluid composition from the reservoir. The apparatus includes: a reservoir; a plunger including a lumen and a proximal end; and a resilient elongated member including a lumen, wherein the reservoir is fluidly connected to the lumen of the resilient elongated member via the lumen of the plunger, and wherein the proximal end of the plunger is slidably positioned within the reservoir. The displaced fluid composition can travel through the lumen of the plunger into the lumen of the resilient elongated member.

In other variations, the method described herein for treating an ocular condition using a delivery system may include: piercing the trabecular mesh of the eye with a cannula; proximally moving a portion of a first roller extending from a first side of the housing to distally extend a slidable elongated member from a retracted position within the cannula, such that the slidable elongated member advances about a Schlem tube in a first direction; and distally moving a portion of the first roller extending from the first side of the housing to proximally retract the slidable elongated member to a retracted position, the delivery system comprising: a housing; a drive mechanism including a first roller having a portion extending from a first side of the housing and a second roller having a portion extending from a second side of the housing; a cannula extending to form the distal end of the housing; and a slidable elongated member slidably positioned within the cannula. In some variations, distally moving the portion of the first roller extending from the first side of the housing may also deliver a fluid composition into the Schlem tube. In some examples, the method may further include proximal movement of a portion of a second roller extending from the second side of the housing to distally extend a slidable elongated member from a retracted position within the sleeve, such that the slidable elongated member advances about the Schlem tube in a second direction, and distal movement of the portion of the second roller extending from the second side of the housing to proximal retract the slidable elongated member back to the retracted position. In some examples, distal movement of the portion of the second roller extending from the second side of the housing may also deliver a fluid composition into the Schlem tube.

A method for using a device to rupture the trabecular meshwork may include: inserting a cannula into the anterior chamber through a corneal or scleral incision; piercing the trabecular meshwork of the eye with the cannula; extending an elastic tool from a retracted position to an extended position; and retracting the cannula from the anterior chamber without retracting the elastic tool. The drive assembly may be configured to advance the elastic tool a first maximum distance without retracting, and may be configured to limit the cumulative advance of the elastic tool to a maximum total distance. In some variations, the first maximum distance may be between 15 mm and 25 mm, and the maximum total distance may be between 35 mm and 45 mm.

In some variations, a method for using a device to rupture the trabecular meshwork of the eye may include: inserting a cannula into the anterior chamber through a corneal or scleral incision; piercing the trabecular meshwork of the eye with the distal tip of the cannula; extending an elastic tool from a retracted position to an extended position; and gradually tearing the trabecular meshwork from the proximal end to the distal end of the body of the elastic tool, said device comprising: a cannula; an elastic tool including a body and slidable within the cannula between a retracted position and an extended position.

The kit described herein may include a first device and a second device. The first device may include a housing, a cannula, an elongated elastic polymer member, a reservoir, and a drive assembly. The cannula may be attached to a distal end of the housing and may include a distal tip. The elongated elastic polymer member may include an inner lumen and a distal end, the distal end being slidable within the cannula between a retracted position and an extended position. The distal end is within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The reservoir may include a fluid composition and is fluidly connected to the inner lumen of the elongated elastic polymer member. The drive assembly may be configured to simultaneously move the elongated elastic polymer member from the extended position to the retracted position and deliver the fluid composition from the reservoir through the inner lumen of the elongated elastic polymer member.

The second device may also include a housing, a sleeve, an elongated elastic polymer member, and a drive assembly. The sleeve may be attached to the distal end of the housing and may include a distal tip. The elongated elastic polymer member may include an inner lumen and a distal end. The distal end is slidable within the sleeve between a retracted position and an extended position, and the distal end is within the sleeve in the retracted position and distal to the distal tip of the sleeve in the extended position. The drive assembly may be configured to move the elongated elastic polymer member from the extended position to the retracted position. The second device may not include a reservoir.

In some variations, the kit described herein may include a device and a tray. The device may include a housing, a cannula, and an elongated, resilient polymer member. The cannula may be attached to a distal end of the housing and may include a distal tip. The elongated, resilient polymer member may include a lumen and a distal end, the distal end being slidable within the cannula between a retracted position and an extended position. The distal end is within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The tray may be configured to removably receive the device. The tray may include a first set of grips and a second set of grips, and the cannula may not contact the tray when the device is in the tray.

In some examples, the device may further include a drive assembly configured to advance the elongated elastic polymer member a first maximum distance without retraction. The device may be configured to limit the cumulative advance of the elongated elastic polymer member to a maximum total distance. In some of these examples, the first maximum distance may be between 15 mm and 25 mm, and the maximum total distance may be between 35 mm and 45 mm.

The method described herein is a method of manufacturing a cannula for use in a Schlemm tube. The method may include creating a bevel at the distal tip of the cannula, sharpening the cannula, and smoothing a portion of the cannula. The distal tip of the cannula may include an inner circumference and an outer circumference edge, and the cannula may include a lumen therethrough. The bevel may traverse the lumen, and creating the bevel may form a proximal and distal end of the distal tip. The sharpened cannula may include a distal end of the sharpened distal tip to create a sharp puncture tip. Smoothing a portion of the cannula may include smoothing a portion of the inner or outer circumference edge. In some variations, the cannula may include stainless steel, nitinol, or titanium hypodermal tubing.

In some variations, the distal end of the grinding tip may include a portion of the outer surface of the grinding sleeve and/or a portion of the outer circumferential edge. In some variations, the sharp piercing tip may be configured to pierce the trabecular meshwork of the eye. In some examples, the sharp piercing tip may include two angled surfaces. In some of these examples, the angle between the two angled surfaces may be between 50 degrees and 100 degrees.

In some examples, smoothing a portion of the inner or outer circumferential edge may include smoothing the inner circumferential edge proximal to the distal tip. In some variations, smoothing a portion of the inner or outer circumferential edge may include smoothing the outer circumferential edge proximal to the distal tip. In some examples, smoothing a portion of the inner or outer circumferential edge may include smoothing both the inner and outer circumferential edges proximal to the distal tip. In some variations, smoothing a portion of the inner or outer circumferential edge may include smoothing the inner circumferential edge distal to the distal tip. In some examples, smoothing a portion of the inner or outer circumferential edge may include smoothing the entire inner circumferential edge and smoothing the outer circumferential edge proximal to the distal tip. In any of these variations or examples, smoothing may include abrasive polishing with a baking soda medium.

In some variations, the manufacturing method may further include applying a protective cap to the sharp puncture tip prior to a polishing step. In these variations, the sharp puncture tip may include an angled surface, and said angled surface may be covered by the protective cap.

In some examples, the manufacturing method may further include polishing the distal tip. In some of these examples, polishing may include electropolishing. In some variations, the method may further include passivating the sleeve. In some of these variations, passivation may remove iron oxide from the sleeve. Additionally, in some of these variations, passivation may include passivation with acid. In some examples, the method may further include roughening at least a portion of the sleeve adjacent to the distal tip. In some of these examples, roughening may include abrasive grinding with a soda ash medium.

In variations of the manufacturing method described herein, the method may further include cutting the sleeve into lengths between 50 mm and 70 mm. In some of these variations, cutting the sleeve may include cutting the sleeve into lengths of 60 mm.

In some examples, the manufacturing method may further include bending a distal portion of the sleeve along its longitudinal axis. In some of these examples, bending the distal portion of the sleeve may include bending the distal portion at an angle between 100 and 125 degrees. In some of these examples, bending the distal portion of the sleeve may include bending the distal portion at an angle of 118 degrees.

In some variations, a method of manufacturing a cannula for use in a Schlemm tube may include: cutting the cannula to a working length; roughening the outer surface of the cannula; creating a bevel at the distal tip of the cannula; grinding the distal tip; applying a protective cap; smoothing a portion of the cannula; bending the cannula; electropolishing the cannula; and passivating the cannula. In some variations, the cannula may include a proximal portion, a central portion, a distal portion, and an inner lumen therethrough, and the distal portion may include the distal tip. In some examples, roughening the outer surface of the cannula may include roughening the outer surface of the central portion of the cannula. In some variations, the distal tip of the cannula may include an inner circumference and an outer circumferential edge, and the cannula may include an inner lumen therethrough. In some examples, the bevel may traverse the inner lumen, and creating the bevel may form the proximal and distal ends of the distal tip. In some variations, grinding the distal tip may further sharpen the distal tip to form a sharp piercing tip. In some examples, applying a protective cap may include applying the protective cap to the sharp puncture tip, and smoothing a portion of the cannula may include smoothing a portion of the inner or outer circumferential edge. In some variations, bending the cannula may include bending the distal portion of the cannula along its longitudinal axis, and electropolishing the cannula may include electropolishing the distal tip. In some examples, passivating the cannula may include passivating the cannula with acid.

Attached Figure Description

Figure 1 shows a stylized cross-sectional view of the eye and some of the structures related to the outflow of aqueous humor from the eye.

Figure 2 depicts a perspective view of an exemplary delivery system for implanting an eye device.

Figure 3 depicts a side view of an exemplary sleeve of the delivery system.

Figures 4A and 4B depict perspective views of exemplary drive assemblies. Figure 4A shows the drive assembly in a handle of a system in a first orientation, and Figure 4B shows the handle in a second flip orientation.

Figures 5A and 5B show perspective views of an exemplary engagement mechanism for delivering an illustrative ocular implant.

Figure 6 shows a perspective view of a fitting mechanism for delivering an illustrative ocular implant, according to a variant.

Figures 7A and 7B show perspective views of engagement mechanisms for delivering illustrative ocular implants, according to other variations.

Figures 8A and 8B depict perspective views of a fitting mechanism for delivering an illustrative ocular implant, according to yet another variant.

Figure 9 depicts a perspective view of another exemplary engagement mechanism for delivering an illustrative ocular implant.

Figures 10A and 10B illustrate exemplary delivery systems for delivering fluid compositions into Schlemm tubes. Figure 10A is a perspective view of the system. Figure 10B is a partial cross-sectional view of the system.

Figures 11A to 11C illustrate exemplary methods for delivering a fluid composition outside of a delivery system.

Figure 12 depicts an exemplary slidable elongated component for delivering a fluid composition.

Figures 13A to 13C show side or perspective views of the sliding elongated component according to other variations.

Figure 14 is a stylized description of an internal method for entering a Schlem tube through a sleeve of an exemplary delivery system.

Figure 15 depicts an exemplary sleeve according to another variant.

Figure 16 is a stylized description of an in-circuit method that enters the Schlem tube from a single point and delivers viscoelastic fluid while simultaneously allowing the fluid delivery elongated component to advance along the 360-degree arc of the tube.

Figure 17 is a stylized description of an in-circuit method that enters the Schlem tube from a single point and delivers viscoelastic fluid while simultaneously allowing the fluid delivery elongated component to advance along the 180-degree arc of the tube in both clockwise and counterclockwise directions.

Figures 18A to 18C illustrate exemplary internal methods for cutting or tearing small beam meshes.

Figure 19 is a flowchart illustrating an exemplary manufacturing method for a sleeve that can be used with the apparatus, systems and methods described herein.

Figure 20 is a perspective view of a variant of the distal tip of the cannula.

Figures 21A and 21B are perspective and front views, respectively, of a variant of the distal tip of the cannula.

Figures 22A and 22B depict perspective views of exemplary drive assemblies for a delivery system. Figure 22C shows a perspective view of a delivery system with an extended, slidable elongated component. Figure 22D shows a perspective view of a delivery system with an extended, slidable elongated component without a housing at the top.

Figure 23A shows a perspective view of an exemplary delivery system for delivering fluid. Figure 23B shows a cross-sectional view of the delivery system of Figure 23A. Figures 23C to 23D show perspective views of the delivery system of Figure 23A without a housing. Figure 23E shows a close-up cross-sectional view of the proximal end of the delivery system of Figure 23A. Figure 23F shows a perspective view of the delivery system of Figure 23A with an extended, slidable elongated member at the top without a housing.

Figure 24 depicts a perspective view of another exemplary delivery system for delivering fluids.

Figures 25A and 25B depict perspective views of an exemplary delivery system having a lock removed (Figure 25A) and inserted (25B) into a handle. Figures 25C and 25D respectively show perspective and cross-sectional views of the lock rotated to allow loading of a reservoir.

Figures 26A and 26B show perspective views of exemplary trays for use with a delivery system (Figure 26A) and a delivery system having a delivery system and a loading tool (Figure 26B). Figure 26C shows an exploded view of an exemplary packaged kit.

Figures 27A and 27B show exemplary kits that include multiple delivery systems.

Figure 28A is a flowchart illustrating an exemplary method for delivering fluid into a Schlemm tube. Figures 28B to 28D depict the delivery of fluid as the slidable elongated component contracts, which is part of the method of Figure 28A.

Figure 29A is a flowchart illustrating an exemplary method for fracturing a trabecular mesh. Figures 29B to 29D depict the fracturing of the trabecular mesh as part of the method of Figure 29A.

Detailed Implementation

This document describes systems and methods for accessing the Schlem tube and for delivering ocular devices, tools, and/or fluid compositions into the tube to reduce intraocular pressure and thereby treat ocular conditions. Certain components of the fluid and system, such as slidable elongated parts, can be used to provide forces for rupturing trabecular tubule tissue, which includes the trabecular meshwork, proximal tubule tissue, Schlem tube, and collecting tube. As used herein, the term “rupture” refers to the delivery of a fluid or system component that alters the volume of tissue in a manner that improves flow through the outflow path of the trabecular tubule. Examples of tissue rupture include (but are not limited to): dilation of the Schlem tube, dilation of the collecting tube, increasing the porosity of the trabecular meshwork, stretching the trabecular meshwork, forming microfractures or perforations in the proximal tubule tissue, removing collagen septa from the Schlem tube, cutting, tearing, or removing trabecular tubule tissue, or a combination thereof.

To better understand the systems and methods described herein, it may be helpful to clarify some of the basic anatomical structures of the eye. Figure 1 is a stylized description of a normal human eye. The anterior chamber (100) is shown as being defined on its anterior surface by the cornea (102). The cornea (102) is connected peripherally to the sclera (104), which is a tough fibrous tissue that forms the protective white shell of the eye. The trabecular meshwork (106) is located on the outer periphery of the anterior chamber (100). The trabecular meshwork (106) extends 360 degrees around the circumference of the anterior chamber (100). Located on the outer peripheral surface of the trabecular meshwork (106) is the Schlemm canal (108). The Schlemm canal (108) extends 360 degrees around the circumference of the meshwork (106). At the apex formed between the iris (110), the meshwork (106), and the sclera (104) is the anterior chamber angle (112).

The system is typically configured for one-handed operation and control by a single operator, and includes one or more features suitable for easy access to the Schlem tube with minimal trauma. Once inside the tube, the system can deliver an eye device, tool, and/or fluid composition. In some variations, the system advances a tool that ruptures the Schlem tube and surrounding tissue without delivering the eye device or fluid composition. For example, the tool can be an elongated component that slides within a cannula for accessing the tube and can extend from the cannula, the elongated component having an outer diameter sized to rupture the tube and surrounding tissue. In some examples, if the system removes the elongated component from the eye while it is inside the Schlem tube, the body of the elongated component can be configured to cut or tear the trabecular meshwork, and/or the distal end of the elongated component can have a splitting assembly to aid in the rupture of the trabecular tubule tissue.

When the device is implanted into the tube, it will typically be configured to keep the Schlem's tube open without substantially interfering with transmural fluid flow through the tube. This can restore, enable, or improve the normal physiological outflow of aqueous humor through the trabecular tubule tissue. Ocular implants such as those disclosed in U.S. Patent No. 7,909,789 and U.S. Patent No. 8,529,622, each of which is incorporated herein by reference in its entirety, can be delivered. In some variations, the implants in U.S. Patent Nos. 7,909,789 and 8,529,622 include a support with at least one perforation that completely traverses the central core of the Schlem's tube without substantially interfering with transmural or longitudinal fluid flow through or along the tube. The ocular device may also rupture the adjacent inner wall of the trabecular meshwork near the tubule or the Schlem's tube. The ocular device can also be coated with medications suitable for treating high intraocular pressure, glaucoma, or early-stage glaucoma, infection, or scarring, angiogenesis, fibrosis, or postoperative inflammation. The ocular device can also be formulated as a solid, semi-solid, or bioabsorbable material.

The system can also be used to deliver fluid compositions, such as saline or viscoelastic fluids. Saline can be used for flushing. Viscoelastic fluids can be used in internal versions of viscoelastic tubulotomy or tubuloplasty procedures to rupture the tubules and surrounding tissue.

I. Systems/Devices

The system described herein can be a one-handed, single-operator control device, typically comprising a universal handle with a gripping portion and a housing having an inner and a distal end. A cannula is typically connected to and extends from the distal end of the housing. The cannula may include proximal and distal curved portions, wherein the distal curved portion has a proximal end and a distal end, and a radius of curvature defined between the ends. In other variations, the cannula may be straight and may not include the distal curved portion. The cannula may also be configured to include: a body; a distal tip having a bevel; and an inner lumen extending from the proximal end through the distal tip. The bevel may directly engage the distal end of the curved portion of the cannula (i.e., the bevel may directly engage the radius of curvature). The system may also typically include a drive assembly partially contained within the housing, the drive assembly including gears that convert rotational movement into linear movement. When the ocular device is to be implanted into a Schlem cannula, the system may further include a slidable positioning element having a proximal end and a distal end, coaxially disposed within the cannula lumen. The system can also be configured to include a slidable elongated component comprising an inner lumen, said slidable elongated component being coaxially disposed within the lumen of the cannula. The system can also be configured to include a fluid assembly in a handle when the fluid composition is delivered into the Schlem tube. The system can be used to deliver fluid compositions such as saline, viscoelastic fluids containing viscoelastic solutions, air, and gases. Suitable markings, colorants, or indicators can be included on any part of the system to aid in identifying the location or position of the distal end of the cannula, positioning elements, engagement mechanisms, ocular devices, or the slidable elongated component. In some examples, the system described herein can be used to perform internal trabeculotomy, internal transluminal trabeculotomy, clear keratotomy, clear transluminal trabeculotomy, internal canal reshaping, and/or clear canal reshaping, and can be used to deliver fluid compositions into the anterior or posterior segment of the eye.

Figure 2 depicts an exemplary eye delivery system. In the figure, the delivery system (200) includes a universal handle (202) having a gripping portion (204) and a housing (206). The housing has a proximal end (208) and a distal end (210). A sleeve (212) is connected to and extends from the distal end (210) of the housing. A drive assembly (214) is substantially contained within the housing (206) and actuates movement of a positioning element (not shown). A port (216) is provided on the distal end of the housing (210) for removable sources connected to the flushing fluid.

In some variations, the delivery system described herein may be entirely disposable. In other variations, a portion of the delivery system may be reusable (e.g., non-patient contact materials, such as a handle), while another portion may be disposable (e.g., patient contact materials, such as cannulas and elongated components). In yet another variation, the delivery system described herein may be entirely reusable.

universal handle

The eye delivery system described herein may include a universal handle capable of single-handed use. For example, the handle may be configured to be used with either the left or right hand, for either the left or right eye, or in a clockwise or counterclockwise direction. That is, the handle may be configured such that the ability to use the delivery system is independent of which hand is used, which eye is being operated on, or in which direction the eye device, tool, or fluid composition is delivered around the tube. For example, the delivery system may be used to deliver an eye device, elongated part, and/or fluid composition into the eye in a clockwise direction, and subsequently, by simply flipping the handle (or, in another variation, by rotating the cannula itself 180 degrees) to a second orientation, it may be used to deliver the same eye device, elongated part, and/or fluid composition in a counterclockwise direction. However, it should be understood that in other variations, the delivery system described herein may be configured for use in specific configurations (e.g., where a single side faces upwards, only in a clockwise direction, only in a counterclockwise direction, etc.). The handle typically includes a gripping portion and a housing. The gripping portion may be raised, recessed, or grooved in certain areas, or textured to improve the user's grip on the handle or enhance user comfort. The housing may comprise an internal portion and a distal end. The internal portion of the housing may contain a drive assembly and positioning elements (both described further below). In some variations, the distal end of the housing includes a fluid port that may provide fluid for rinsing the surgical area or purging air from the system.

The universal handle can be made of any suitable material, including but not limited to fluoropolymers; thermoplastics such as polyetheretherketone, polyethylene, polyethylene terephthalate, polyurethane, nylon, etc.; and silicone. In some variations, the housing or a portion thereof can be made of a transparent material. Materials with suitable transparency are typically polymers such as acrylic copolymers, acrylonitrile butadiene styrene (ABS), polycarbonate, polystyrene, polyvinyl chloride (PVC), polyethylene terephthalate (PETG), and styrene-acrylonitrile (SAN). Acrylic copolymers that may be particularly useful include (but are not limited to) polymethyl methacrylate (PMMA) copolymers and methyl methacrylate styrene (SMMA) copolymers (e.g., Zylar acrylic copolymers). In variations where the universal handle is reusable, the handle can be made of materials that can be sterilized (e.g., via autoclaving), such as heat-resistant metals (e.g., stainless steel, aluminum, titanium).

The length of a standard handle generally ranges from about 1 inch (2.5 cm) to about 20 inches (50.8 cm). In some variations, the length of the standard handle may be between about 4 inches (10.2 cm) and 10 inches (25.4 cm). In some variations, the length of the standard handle is about 7 inches (17.8 cm).

casing

The cannula of an ocular delivery system is typically attached to and extends from the distal end of a housing, and is generally configured to provide easy and minimally invasive access to the Schlem canal using a minimally invasive endoscopic approach. The cannula may be fixedly attached to the distal end of the housing, or in other variations, it may be rotatably attached to the distal end of the housing. In variations of delivery systems where the handle is reusable and the cannula is disposable, the cannula may be removably attached to the distal end of the housing. Some variations of the cannula may include proximal and distal curved portions, wherein the distal curved portion has proximal and distal ends, and a radius of curvature defined between the ends. However, it should be understood that in other variations, the cannula may be straight and may not include a distal curved portion. The cannula may also be configured to include: a body; a distal tip having a bevel and a sharp puncture tip; and an inner lumen extending from the proximal end through the distal tip. When the cannula includes a distal curved portion, the bevel may directly engage the distal end of the curved portion of the cannula (i.e., the bevel may directly engage the radius of curvature). In some variations, the sharp puncture tip may include one or more angled surfaces, as described in more detail below.

The cannula can be made of any suitable material having sufficient rigidity to allow its advancement through the eye wall and anterior chamber. For example, the cannula can be formed from metals (e.g., stainless steel, nickel, titanium, aluminum), or alloys thereof (e.g., nickel-titanium alloys), polymers, or composite materials. Exemplary polymers include, but are not limited to, polycarbonate, polyetheretherketone (PEEK), polyethylene, polypropylene, polyimide, polyamide, polysulfone, polyether block amide (PEBAX), and fluoropolymers. In some cases, it may be advantageous to coat the cannula with a lubricating polymer during surgery to reduce friction between the ocular tissue and the cannula. Lubricating polymers are well known in the art and include (but are not limited to) polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, fluoropolymers (including polytetrafluoroethylene (PTFE) or polyoxyethylene), and polyethylene oxide. In variations where the cannula is reusable, it can be made of materials that may be sterilized (e.g., via autoclaving), such as heat-resistant metals (e.g., stainless steel, aluminum, titanium).

The cannula typically has an outer diameter sized to allow access to the lumen of the Schlemm canal while minimizing obstruction of the surgeon's view. Therefore, the outer diameter may range from approximately 50 micrometers to approximately 1000 micrometers. In some variations, the outer diameter may range from approximately 150 micrometers to approximately 800 micrometers. The cannula also has an inner diameter, which may range from approximately 50 micrometers to approximately 400 micrometers. The cannula can also be formed with any suitable cross-sectional curve, such as annular, elliptical, triangular, square, rectangular, etc.

The cannula can be configured to comprise multiple sections or components. A cannula having a body, a distal bend (having a proximal and a distal end, defined by a radius of curvature between said ends), and a bevel at the distal tip of the cannula (which directly engages the distal end of the bend of the cannula) may be particularly suitable for access to the lumen of the Schlem tube. Here, the body (the straight portion of the cannula) may have a length ranging from about 5 mm to about 50 mm, about 10 mm to about 30 mm, or about 14 mm to about 20 mm. In some variations, the body may have a length of about 18 mm. The cross-sectional shape of the distal bend of the cannula may be uniform, or it may become tapered closer to the distal end to facilitate access to the Schlem tube. The radius of curvature of the distal bend may be adapted to facilitate tangential access (as well as precise and minimally invasive access) to the Schlem tube, and may range from about 1 mm to about 10 mm or from about 2 mm to about 5 mm. In one variation, the radius of curvature is about 2.5 mm. The sleeve may also have an angular span suitable for facilitating access to the Schlemm tube, and said angular span may be in the range of about 70 degrees to about 170 degrees or about 100 degrees to about 150 degrees. In one variation, the angular span is about 120 degrees.

The size, shape, geometry, etc., of the bevel at the distal end of the curved portion of the cannula can be advantageous in allowing easy and minimally invasive access to the Schlem tube. In this respect, and as described in more detail below, a bevel having a radius of curvature that directly engages the distal end of the cannula can be particularly useful.

In other variations, the sleeve may include a shorter straight segment that connects to the distal end of the distal bend of the sleeve (e.g., at the end of the radius of curvature). Here, the bevel engages the straight segment instead of the radius of curvature. The length of the straight segment may range from about 0.5 mm to about 5 mm. In some variations, the length of the straight segment ranges from about 0.5 mm to about 3 mm or from about 0.5 mm to about 1 mm. The length of the straight segment may also be less than about 0.5 mm, for example, it may be about 0.1 mm, about 0.2 mm, about 0.3 mm, or about 0.4 mm. In a variation where the bevel directly engages the distal end of the bend of the sleeve (i.e., the bevel directly engages the radius of curvature), the sleeve does not have a straight segment (the length of the straight segment is zero).

Having a steep and short bevel to minimize the distance any ocular device would have to travel when implanted into the tube can also be useful. Exemplary bevel angles can range from about 10 degrees to about 90 degrees. In some examples, the bevel angle can range from about 10 degrees to about 50 degrees. In one variation, the bevel angle is about 35 degrees, while in another variation, the bevel is about 25 degrees. The bevel can also be oriented in any suitable direction. For example, the bevel can be oriented so that it opens toward the surgeon, or it can be reversed to open away from the surgeon or in any plane in between.

As described in more detail below, in some variations, the sleeve is configured to include a steep section and another blunt (e.g., deburred) section. This dual-surface configuration of the sleeve can be advantageous because it provides easier tube entry by piercing the mesh during the retraction of the elongated component into the sleeve, while also providing a gentle, dispersed force on the elongated component to avoid cutting or breaking it due to the retraction force. For example, as shown in Figure 15, the distal end of the sleeve (1500) may have a sharp piercing tip (1502) and a smooth edge (1504) that defines a portion of an opening (1506) through which a slidable elongated component (not shown) can advance and retract. As described in more detail with respect to Figures 19, 20, 21A to 21B, the sharp tip (1502) may be formed by a combination of multiple bevels, and the smooth edge (1504) may be produced by smoothing or deburring the inner and/or outer circumferential edges of the distal tip. Additionally, in some embodiments, the inner and/or outer surfaces of the elongated member adjacent to the opening (1506) may be polished smooth. The method of fabricating the sleeve is described in more detail below.

The cannula of the exemplary delivery system is shown in more detail in FIG. 3. Here, the cannula (300) includes a proximal end (302), a distal bend (304), a body (314), and a distal tip (306). The distal bend (304) has a proximal end (308) and a distal end (310), and a radius of curvature (R) defined between the ends (308, 310). The distal bend (304) also has an inner radius (320) defined by the surface of the cannula closest to the center of the radius of curvature (R), and an outer radius (322) defined by the surface of the cannula further away from the center. A bevel (312) at the distal tip (306) directly engages the distal end (310) of the bend of the cannula. In other words, the bevel (312) may abut the distal end (310) of the bend of the cannula. As previously stated, this configuration of the distal curved portion (304) and the ramp (312) can be beneficial or advantageous in allowing easy, non-invasive, and controlled access into the Schlemm tube. The angle of the ramp can also be important. Generally, a shorter ramp can be advantageous. The ramp (312) can include an angle (A) between about 5 degrees and about 85 degrees. In some variations, the angle (A) can be about 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, or 85 degrees. In some variations, the angle (A) can be between about 23 degrees and about 27 degrees. In the variation shown in Figure 3, the ramp angle (A) is about 25 degrees.

Figure 20 depicts a perspective view of the distal tip (2002) of a sleeve (2000) including a bevel (2014). The distal tip (2002) may be cut or ground at an angle to create the bevel (2014). As shown, the beveled distal tip (2002) includes a proximal end (2008), a distal end (2010), and an elongated opening (2012) having an elliptical shape rather than a circular shape. The distal tip (2002) may include an angled elliptical inner cavity opening such that the top of the elliptical opening is closer to the proximal portion of the sleeve than the bottom of the elliptical opening. The inner and outer circumferential edges (2004, 2006) are also shown in Figure 20.

Figures 21A and 21B depict a perspective view and a front view, respectively, of a variation of the distal tip (2100) of a cannula, including a bevel (2102) and a sharp puncture tip (2114). As shown herein, the distal tip (2100) also includes a proximal end (2108), a distal end (2110), inner and outer circumferential edges (2104, 2106), and an internal opening (2112). The sharp puncture tip (2114) may include two angled surfaces (2116) converging to form a cusp. The angled surfaces (2116) may have any suitable angle that produces the sharp puncture tip (2114). For example, in some examples, the angled surface (2116) may have an angle (B) of about 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, or 50 degrees, between about 25 degrees and about 50 degrees, or between about 37.5 degrees and about 42.5 degrees, relative to the longitudinal axis of the distal tip (2100). In some examples, the angle (B) may be about 40 degrees. Thus, in some variations, the angle between the two angled surfaces (2116) may be between about 50 degrees and about 100 degrees, and in some examples, the angle between the two angled surfaces (2116) may be about 80 degrees. It should be understood that although the distal tip (2100) is depicted with two angled surfaces, a distal tip with a single angled surface may also be used.

Slender parts

The delivery system described herein may include a slidable elongated member coaxially disposed within a cannula lumen. The elongated member used in the system described herein may have various configurations and may or may not include a lumen. The elongated member may or may not be configured to deliver a fluid composition.

An elongated member may be coaxially disposed within and slidable within the lumen of the delivery system described herein. When the elongated member is in the retracted position relative to the cannula, the distal end of the elongated member may be positioned within (i.e., close to) the distal tip of the cannula. When the elongated member is in the extended position relative to the cannula, the distal end of the elongated member may be positioned outside (i.e., distal) the distal tip of the cannula. The length by which the elongated member extends beyond the distal tip of the cannula may correspond to the distance by which the elongated member may traverse around the Schlem tube (e.g., to rupture the Schlem tube and/or surrounding trabecular tubules, and/or to deliver the fluid composition). In variations of the delivery system configured to deliver the fluid composition, the length traversed by the elongated member may correspond to the length of the fluid composition delivered around the Schlem tube. In variations of the delivery system configured to tear or cut the trabecular meshwork, the length traversed by the elongated member may correspond to the length by which the trabecular meshwork is cut or torn. In some variations, this length may be between about 1 mm and about 50 mm. In some of these variations, the length may be between approximately 10 mm and approximately 40 mm, between approximately 15 mm and approximately 25 mm, between approximately 16 mm and approximately 20 mm, between approximately 18 mm and approximately 20 mm, between approximately 19 mm and approximately 20 mm, between approximately 18 mm and approximately 22 mm, approximately 20 mm, between approximately 30 mm and approximately 50 mm, between approximately 35 mm and approximately 45 mm, between approximately 38 mm and approximately 40 mm, between approximately 39 mm and approximately 40 mm, or approximately 40 mm. The elongated component can be moved between an extended position and a retracted position using a drive assembly of a delivery system, as described in more detail below.

The elongated component may be sized to allow it to advance through a cannula and into a portion of the Schlem's canal (e.g., 0 to 360 degrees of the canal) to rupture trabecular tubule tissue, vascular stents, and/or apply tension to the canal, and/or deliver a fluid composition. The elongated component may be made of any suitable material that imparts the necessary elasticity and pushability for introduction through the ocular wall, into the Schlem's canal, and/or navigation through other ocular structures. For example, the elongated component may comprise a polymer (e.g., nylon, polypropylene); a polymer reinforced with metal wire, braid, or coil; a polymer-metal composite; or a metal, such as stainless steel, titanium, shape memory alloy (e.g., nitinol), or an alloy thereof. In a reusable variant, the elongated component may be made of a material that can be sterilized (e.g., via autoclaving), such as a heat-resistant metal (e.g., stainless steel, aluminum, titanium). The elongated component can be straight, possessing sufficient flexibility and pushability to guide the annular Schlemm tube, or it can be pre-shaped to have a radius of curvature of approximately 2 mm to 10 mm or approximately 6 mm (i.e., the approximate radius of curvature of the Schlemm tube in adults), thereby making it easier to partially or entirely encircle the Schlemm tube. In some variations, the elongated component can be configured to advance on or along the guide wire.

In some variations, it may be desirable for the elongated component to possess one or more features to improve its imaging. For example, the elongated component may be colored (e.g., red, orange, yellow, green, blue, purple, etc.). Alternatively, illumination beacons, optical fibers, side-illuminated optical fibers, cold light, fluorescence, etc., can be used to improve imaging. For instance, an optical fiber may travel along the body of the elongated component to deliver light to its distal tip, which can improve the imaging of the distal tip as it advances or contracts around the Schlem tube.

In some variations, the elongated component can be sized to have an outer diameter sufficient to rupture the Schlem tube and surrounding trabecular tubules. The outer diameter can range from about 25 micrometers to about 1000 micrometers, about 25 micrometers to about 500 micrometers, about 50 micrometers to about 500 micrometers, about 150 micrometers to about 500 micrometers, about 200 micrometers to about 500 micrometers, about 300 micrometers to about 500 micrometers, about 200 micrometers to about 250 micrometers, about 150 micrometers to about 200 micrometers, or about 180 micrometers to about 300 micrometers. In some examples, an outer diameter of about 240 micrometers may be advantageous for the elongated component.

In some variations, the distal end of the elongated component may be configured as a blunt bevel, a non-invasive tip, an enlarged non-invasive tip, etc., to facilitate the advancement of the elongated component through the Schlem tube. In some of these variations, the distal end may include a blunt, umbrella-shaped non-invasive tip. In other variations, the distal portion of the elongated component may optionally include destructive components, such as notches, hooks, barbs, rough surfaces, or combinations thereof, to rupture the trabecular portion or trabecular network of the Schlem tube. One or more protrusions originating from the elongated component may further rupture the trabecular portion or trabecular network of the Schlem tube, and thus increase the permeability of aqueous humor through the trabecular network into the Schlem tube. In some examples, the elongated component may also deliver energy (e.g., ultrasonic energy, radiofrequency energy (e.g., for electrocautery, electroablation), electromagnetic radiation, light energy (e.g., via optical fiber)) to the trabecular tubule tissue.

In some examples, the elongated component may comprise a filament (e.g., filaments include nylon, polypropylene, metal, etc.). For example, the elongated component may comprise a nylon monofilament. Exemplary ranges for filament fineness can be from about 50 micrometers to about 300 micrometers. The filament may be configured to advance through all or part of the Schlem tube. In some examples, the body of the filament may be configured to cut or tear through the trabecular mesh as it is removed from the tube from the eye. In other examples, the filament may be configured to immediately rupture the trabecular tubule tissue upon entering or contracting from the Schlem tube. In still other examples, the filament may be configured to remain within the tube to continuously deliver tension to the mesh and keep the tube open.

In some variations, the elongated component may include an inner lumen. For example, in one variation, the elongated component may include a microcatheter (e.g., a nylon microcatheter). In some examples where the elongated component includes an inner lumen, the elongated component may be configured to deliver a fluid composition. The fluid composition may travel through the inner lumen of the elongated component and may be delivered through an opening in the inner lumen. For example, as shown in FIG12, the elongated component (1200) may be a flexible tube having an inner lumen in fluid communication with an opening at a distal tip (1202). In some variations, the distal end of the elongated component may be configured or modified to facilitate delivery of the fluid composition into a Schlemm tube. For example, the distal end of the elongated component may include a cut configured as a half-tube. Alternatively or additionally, for the opening at the distal tip, the elongated component may optionally include a plurality of openings extending through its walls, said plurality of openings being spaced apart along the axial length of the elongated component. In this variation, the fluid composition may be delivered from a reservoir through an opening in the elongated component and into a Schlemm tube. This lateral jetting of the fluid (e.g., a viscoelastic fluid) can, in some cases, enhance the rupture of the outflowing tissue and increase the permeability of the aqueous humor. It should be understood that the openings can have any suitable number, size, and shape, and are spaced apart in any suitable manner along the axial length of the elongated member (including the distal tip).

Drive assembly

Delivery systems typically include a drive assembly. The drive assembly of a delivery system is generally configured to move an eye device, an elongated component, and/or a fluid composition into a Schlemm tube. In some variations, the drive assembly may also be configured to position the eye device within the tube, including a device for entering and retracting the device from the tube. The drive assembly may be at least partially contained within a housing and may include any suitable components or combinations of components capable of providing general functionality to the handle.

The drive assembly can convert external input (e.g., movement of a user's thumb or finger) into movement of one or more components of the delivery system. More specifically, the drive assembly can cause a slidable elongated member to extend away from the sleeve, and/or can cause the slidable elongated member to retract proximally into the sleeve. The drive assembly can also optionally cause a fluid composition to be delivered from a reservoir through the elongated member and/or the sleeve.

The same actuating mechanism can be used to actuate two or more of these effects (i.e., extending the slidable elongated member, retracting the slidable elongated member, and/or delivering a fluid composition). This allows the delivery system to be used with one hand. For example, if the actuating mechanism includes a rotatable element (e.g., one or more rollers, as in the variations described herein), then rotating the rotatable element in a first direction can cause extension of the slidable elongated member, and rotating the rotatable element in a second direction can cause retraction of the slidable elongated member. If the delivery system is configured to deliver a fluid composition, then rotating the rotatable element (e.g., in the second direction) can also cause delivery of the fluid composition. Delivery of the fluid composition can be synchronized with movement (e.g., retraction) of the slidable elongated member. In some of these examples, the fluid composition can be delivered to a portion of the Schlem tube into which the slidable elongated member has advanced; that is, the fluid composition can be delivered to the Schlem tube at the same angle and length as the extension of the elongated member. When the fluid composition is synchronized with the contraction of the elongated component, the fluid composition can replace the slidable elongated component during contraction and can expand the Schlem tube and/or the collection tube located in the Schlem tube. Furthermore, the amount of fluid delivered can be related to the amount of movement of the elongated component; that is, for a fixed amount of movement of the elongated component (e.g., contraction distance) and for a fixed amount of rotation of the rotatable element, a predetermined, fixed volume of fluid composition can be delivered via the elongated component (e.g., delivered beyond the distal end of the elongated component).

In some variations, the drive mechanism can be configured such that the delivery system can only be used once—that is, the drive mechanism can prevent, for example, a sliding elongated component from extending again after extending and/or retracting a predetermined amount. Exemplary mechanisms that can convert external input into motion of one or more components of the delivery system are described in more detail below.

In some variations, the drive assembly includes components that convert rotational motion into linear motion. For example, the drive assembly may include a linear gear and a pair of pinion mechanisms. The linear gear may have teeth on its surface that mesh with corresponding teeth on the pinion. Each of the pinion mechanisms may also be connected to a rotatable component (e.g., a roller). This connection may be achieved using a pin and nut, the pin being screwed through a central opening in both the rotatable component and the pinion, and the nut securing the rotatable component and pinion in such a way that rotation of the rotatable component also causes rotation of the pinion (and vice versa). The roller may be attached to the pinion by, for example: 1) molding the roller and pinion as a single part using plastic injection molding; 2) sliding the roller onto the pinion and securing it with adhesive; or 3) sliding the roller onto the pinion and securing it mechanically with a fastener or "press-fit," wherein the roller presses against the pinion and friction keeps it in place. In all the aforementioned scenarios, the roller and pinion may rotate coaxially in the same direction and at the same angular rate. In some variations, each of the pinion mechanisms is connected to at least two rotatable components. In other variations, the drive assembly may be configured to include a single rotatable component, multiple rotatable components, or no rotatable components. The rollers may have markings or colorings to indicate the degree or direction of advance.

One variation of the drive assembly included in a universal handle comprises a linear gear, a pair of pinion mechanisms, and two rotatable components connected to each pinion (for a total of four rotatable components). In other variations, the drive assembly comprises a linear gear and a single pinion mechanism with two associated rollers. In a variation with a pair of pinion mechanisms, the pinion mechanism and associated rollers are positioned on either side of the linear gear. The pinion and linear gear are in contact with each other, i.e., the teeth of the pinion directly mesh with corresponding teeth on the linear gear, and the roller on one side of the linear gear contacts the roller on the opposite side of the linear gear. At least a portion of the rollers on each side of the linear gear extends outside the housing. In this variation, the drive assembly can be operated with one hand in a first configuration and subsequently with the same hand or the other hand when flipped to a second configuration. This flexible drive assembly can be easily used by right-handed or left-handed surgeons and can also be used during surgery with the handle flipped, such that the cannula faces a first direction in the first part of the surgery and a second direction in the second part. In another variation, the drive assembly may include a rotatable component on one side of the handle and the "universal" feature of the handle provided by a cannula that is rotatable rather than flipped.

In the variation shown in Figure 4A, the delivery system (400) comprises a drive assembly (402) having a linear gear (e.g., a rack) (404) and a pair of pinion mechanisms (406). Both the linear gear and the pinion mechanisms have teeth that mesh with each other to convert the rotational motion of the pinion mechanisms (406) into the linear motion of the linear gears (404). Of the four rotatable components in total, each of the pinion mechanisms (406) is connected to two rotatable components (shown in the diagram as rollers (408)). The rollers (408) extend outside the housing (414) of the delivery system (400), and thus can be rotated by one or more surgeons' fingers to correspondingly rotate the pinion mechanisms (406) and thus advance or retract the linear gears (404). The rollers (408) are coaxial with and rotate in conjunction with the pinion mechanisms (406). Movement of the linear gear (404) causes the positioning element (410), coaxially positioned within and slidable therein, to advance or retract. Figure 4B illustrates the system of Figure 4A in a second flip orientation. In the orientation of Figure 4A, the cannula is oriented with a clockwise curvature, while in the orientation of Figure 4B, the cannula is oriented with a counterclockwise curvature. The extension of the roller (408) outside either side of the housing (414) allows the delivery system (400) to be used in either orientation, with either hand, and to either of the patient's eyes. That is, the orientation of Figure 4B can be used with the opposite hand or the same hand as the orientation of Figure 4A, except when a different cannula insertion direction is required (e.g., if a counterclockwise cannula insertion is performed with the system in Figure 4A, then a clockwise cannula insertion is performed).

Another variation of the drive assembly is shown in two different perspective views in Figures 22A and 22B. As depicted herein, the drive assembly (2202) may include a linear gear (e.g., a rack) (2204) and a pair of pinion mechanisms (2206). Both the linear gear and the pinion mechanisms have teeth that mesh with each other to convert the rotational motion (of the pinion mechanisms) into the linear motion (of the linear gear). More specifically, the linear gear (2204) may include teeth on both a first side (2220) and a second side (2222), wherein the teeth on the first side mesh with a first pinion mechanism and the teeth on the second side mesh with a second pinion mechanism. For a total of four rotatable components, each of the pinion mechanisms (2206) is connected to two rotatable components (shown in the figures as rollers (2208)). The rollers (2208) are coaxial with and rotate in conjunction with the pinion mechanisms (2206). The drive assembly may include one or more features to stabilize the pinion mechanism or otherwise hold it in place. For example, the drive assembly (2202) may include roller spacers (2216) configured to rest between the axles (2218) of the pinion mechanism. Rotation of one or more rollers (2208) may cause translation of the linear gear (2204).

As shown in Figures 22C and 23A-23B, the roller (2208) can extend out of the housing (2334) of the delivery system, allowing the roller to be rotated by the surgeon to correspondingly rotate the pinion mechanism (2206), and thus cause the linear gear (2204) to advance or retract. The cannula (2344) can slide within the linear gear (2204), such that the cannula and roller are fixed relative to each other and relative to the housing (2334), while the linear gear (2204) translates relative to the housing. Since the linear motion of the linear gear (2204) can be generated by the rotational motion of either of the two pinion mechanisms (2206), which can then be generated by rotating either of the rollers (2208) extending from the housing (2334), the delivery system (2300) can be easily operated with one hand, with either the first or second side facing upwards, and thus the cannula (2344) facing either the first or second direction.

In other variations, one or two pinion mechanisms may be able to disengage from the linear gear by biasing their position away from the axis. This action separates the pinion teeth from the linear gear teeth to prevent movement of the linear gear. The pinion mechanism may also be able to prevent rotation by engaging interlocking pins or features that prevent the roller from rotating.

Other variations of the drive assembly may not employ a transition from rotary to linear motion. For example, a slide (e.g., a finger slide) on a handle with a gear (e.g., a linear gear as previously described) fixedly or detachably attached to a housing within the handle. Here, the drive assembly can be configured such that forward or retracting sliding causes forward or retracting of the eye device and/or elongated component, and/or delivery of the fluid composition into the Schlemm tube. In yet another variation, a pressable or squeezeable button may be used instead of a slide, or a foot pedal may be used to deliver the eye device, tool, and/or fluid composition.

To extend and contract slender components

In some variations, the proximal end of the elongated component may be fixed relative to a portion of the drive assembly (e.g., a linear gear (2204)), while the distal end may be slidably and coaxially positioned within the sleeve cavity. When the elongated component does not include a cavity (e.g., it is a filament), in some examples the elongated component may be attached to the drive assembly via coiling. When the elongated component includes a cavity, in some examples the elongated component may be coupled to the drive assembly (e.g., via adhesive) to keep the cavity of the elongated component unobstructed. The sleeve may then be securely attached to the housing. In variations of the delivery system where the handle is reusable and the sleeve and elongated component are disposable, the disposable assembly, including the elongated component pre-loaded within the sleeve, may be attached to the reusable handle via any suitable mechanism (e.g., a threaded fastener or snap-fit feature).

As a portion of the drive assembly moves proximally or distally within the housing, this causes a corresponding movement of the elongated member relative to the sleeve. That is, movement of a portion of the drive assembly toward the sleeve (i.e., toward the distal end of the housing) causes the elongated member to move from a retracted position to an extended position, and movement of a portion of the drive assembly away from the sleeve (e.g., toward the proximity of the housing) causes the elongated member to move from an extended position to a retracted position. An example of the elongated member in the extended position is shown in Figures 22C through 22D. As shown in the view of Figure 22D with the top of the housing (2334) removed, the linear gear (2204) is in the distal position. Therefore, the elongated member (2346) extends from the sleeve (2344).

Storage tank

When the fluid composition is delivered into a Schlemm tube, the system typically includes a reservoir. The reservoir may contain materials for delivering various fluid compositions. An exemplary fluid composition includes physiological saline and a viscoelastic fluid. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, derivatives thereof, or mixtures thereof, or solutions thereof. In one variation, the viscoelastic fluid includes sodium hyaluronate. In another variation, the viscoelastic composition may further include a pharmaceutical agent. For example, the viscoelastic composition may contain substances suitable for treating glaucoma, reducing or lowering intraocular pressure, reducing inflammation, preventing infection, fibrosis, scarring, coagulation, thrombosis, hemorrhage, or angiogenesis. Pharmaceutical agents, such as antimetabolites, vasoconstrictors, anti-VEGF agents, steroids, heparin, anti-inflammatory agents, nonsteroidal anti-inflammatory drugs (NSAIDs), other anticoagulants, fibrinolytic compounds, biological agents, and gene therapy drugs, may also be delivered in combination with the viscoelastic composition. Examples of glaucoma pharmaceutical agents include prostaglandins, beta-blockers, miotics, alpha-adrenergic agonists, or carbonic anhydrase inhibitors. Anti-inflammatory drugs such as NSAIDs, corticosteroids, or other steroids can be used. For example, steroids such as prednisolone, prednisone, cortisone, cortisol, triamcinolone, or shorter-acting steroids can be used. Examples of antimetabolites include 5-fluorouracil or mitomycin C. Examples of drugs or antibodies that prevent angiogenesis include bevacizumab, ranibizumab, etc. In yet another variation, the system delivers only the drug and not the viscoelastic composition. A saline solution can also be the fluid used. In yet another variation, the system can be configured to deliver a gas, such as (but not limited to) air, or an expanding gas (e.g., SF6, C3F8).

In some variations, the reservoir may be at least partially defined by the fluid assembly and housing, as well as a linear gear within the handle. The fluid assembly may be made of any suitable material previously mentioned for the sleeve and housing. The volume of fluid contained within the reservoir (in microliters) may range from about 2 μl to about 1000 μl, or from about 2 μl to about 500 μl. In some variations, the reservoir volume may range from about 50 μl to about 100 μl.

The fluid composition can be preloaded into or loaded into a reservoir before use of the system (e.g., at the start of an ophthalmic procedure), allowing fluid delivery via a single device and by a single user. This contrasts with other systems that use forceps or other advancing tools to insert the fluid delivery catheter into the Schlemm tube and/or devices containing viscoelastic fluids, either separately or independently of the delivery catheter or advancing tool, which require connection to the delivery catheter or advancing tool during surgery, for example, by an assistant or the surgeon's hand, while the delivery catheter or advancing tool is held by the surgeon's other hand. For example, a loading assembly can be provided on the fluid assembly for transferring the fluid composition into the reservoir. The loading assembly can have any suitable configuration that provides a reversible fastener to the system for the fluid container (e.g., syringe, cartridge, etc.) and loads the fluid composition into the reservoir. The loading assembly can be a Luer connector or include a one-way valve.

Figures 23A through 23F illustrate exemplary delivery systems including a reservoir. The delivery system (2300) includes a fluid assembly (2316) comprising a reservoir (2302), shown in Figures 23A, 23B, and 23E, and in Figures 23C and 23D, and in Figure 23F, to some extent lacking a housing (2334). In one exemplary method, the fluid composition may be loaded into the reservoir (2302) via a proximal opening (2328) through a proximal seal (2318). As best shown in Figure 23E, the distal end of the reservoir (2302) may be formed by a plunger (2338) (explained in more detail below) and a distal seal (2354).

The proximal seal (2318) may be a mechanical seal positioned proximal to the reservoir (2302) and includes a ball bearing (2324) that is spring-biased against an O-ring or washer (2330) to close and seal the reservoir. A loading tool (2326) (e.g., a nozzle) may be used to open the seal by pressing against the ball bearing (2324) to move it proximal to the open position. When the proximal seal (2318) is open, a fluid composition may be loaded into the reservoir. After loading the fluid composition, the loading tool (2326) may be removed, allowing the ball bearing (2324) to return to its closed position. A close-range cross-sectional view in Figure 23E shows the proximal opening (2328) and the ball bearing (2324). An O-ring or washer (2330) is positioned between the ball bearing (2324) and the spring (2332), such that a force from the spring presses the ball bearing into the washer to form a seal between the ball bearing and the washer in the closed position. A loading tool (2326) is configured to be inserted into a proximal opening (2328) to press against the ball bearing (2324). A distal orientation force on the ball bearing (2324) moves its distal end to the open position, compresses the spring (2332), and creates an opening between the ball bearing and the washer (2330) through which a fluid composition can flow. When the loading tool (2326) is removed from the proximal opening (2328), the spring (2332) pushes the proximal end of the ball bearing (2324) back to the closed position.

It should be understood that, in other variations, the reservoir may include other types of seals that allow the fluid composition to be loaded into the reservoir. For example, Figure 24 depicts an alternative variation of the delivery system (2400) in which the seal includes a membrane (e.g., a silicone membrane). As shown, the fluid composition may be loaded into the reservoir (after moving an optional lock (2404)) by piercing the membrane with a needle (2402) (e.g., a 25 gauge needle). In yet another variation, the delivery system described herein may be configured to receive a pre-filled cartridge containing the fluid composition. For example, the handle and fluid assembly may be configured such that the pre-filled cartridge can be inserted into the fluid assembly.

To load the reservoir, it may be necessary to at least temporarily hold the fluid assembly in place to allow distal forces to be applied to the seal. In some variations, the delivery system may include a lock configured to hold the fluid assembly in place as the fluid composition is injected into the reservoir. However, it should be understood that in other variations, the delivery system may not include a lock. In variations with a lock, it may be necessary to allow the lock to be removed from the delivery system (or otherwise release the fluid assembly) to allow translation of the fluid assembly relative to the housing after loading into the reservoir. Translation of the fluid assembly may allow extension of slidable elongated parts and/or injection of the fluid composition during the procedure, as described in more detail herein.

In variations of the delivery system with a lock, the lock may optionally additionally function as a cover protecting the distal opening of the reservoir. In these variations, the lock may include a first configuration and a second configuration, in which the lock both holds the reservoir in place and covers the proximal opening of the reservoir, and in the second configuration, the lock holds the reservoir in place but allows access to the proximal opening of the reservoir so that the reservoir can be loaded with the fluid composition. In some examples, the lock can be rotated from a first position to a second position.

Figures 25A to 25D illustrate an exemplary lock (2502). As shown herein, the lock (2502) may include a pin (2508) configured to be inserted into an opening (2504) in a handle (2506) of a delivery system (2500). In a first configuration shown in Figure 25B, the lock (2502) may be inserted into the opening (2504) in the handle and may cover a proximal opening (2510). The lock (2502) may include a protrusion (2518) configured to engage with the proximal opening (2510) to stabilize the lock in the first configuration. In a second configuration shown in Figures 25C to 25D, the lock (2502) may remain inserted into the opening (2504) but may pivot within the opening to expose the proximal opening (2510) thereby allowing loading of the reservoir (2512). When the pin (2508) is inserted into the opening (2504), it restricts the movement of the reservoir (2512) relative to the housing. This allows the loading tool (2514) to apply force through the proximal opening (2510) to open the proximal seal (2516) of the reservoir (2512) without the reservoir sliding distally within the handle (2506). Restricting the movement of the reservoir (2512) relative to the handle (2506) prevents movement of the reservoir or other internal components of the delivery system prior to use (e.g., during transport). Once loading of the reservoir (2512) is complete, the lock (2502) can be removed from the opening (2504), as shown in Figure 25A, at which point the reservoir (2512) is no longer restricted from moving relative to the housing by the lock.

Delivery fluid composition

The delivery system described herein is configurable to deliver fluid to the Schlem tube. The fluid can be delivered in a volume that provides a force sufficient to rupture the Schlem tube and surrounding trabecular tubule tissue. Exemplary destructive volumes may be about 1 μl, about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl, about 11 μl, about 12 μl, about 13 μl, about 14 μl, about 15 μl, about 16 μl, about 17 μl, about 18 μl, about 19 μl, or about 20 μl. In some variations, the destructive volume of fluid may range from about 1 μl to about 50 μl, or from about 20 μl to about 50 μl.

As mentioned above, the elongated component can be coaxially positioned within the cannula lumen. In variations of the delivery system configured to deliver a fluid composition, the elongated component may include a lumen. The lumen of the elongated component may be operatively connected to a reservoir for delivering the fluid composition into the Schlem tube. The elongated component typically has a proximal end, a distal end, and a wall defining the lumen extending therethrough. However, in some examples, the delivery system does not have an elongated component conduit, and the fluid composition is delivered solely through the cannula. In other examples, two elongated components may be used, each advancing through the tube simultaneously in both clockwise and counterclockwise directions, to more rapidly insert the catheter into the Schlem tube and deliver treatment.

When the delivery system is used to deliver a fluid composition, the fluid composition may be pre-loaded in the system's reservoir or loaded into the reservoir before use of the system. Exemplary delivery systems for delivering fluid compositions into Schlemm tubes are shown in Figures 10A and 10B. Referring to Figure 10A, the delivery system (1000) includes a universal handle (1002) with a gripping portion (1004) and a housing (1006). The housing (1006) has a proximal end (1008) and a distal end (1010). A sleeve (1012) is connected to and extends from the distal end of the housing (1010). A drive assembly (1014) is substantially contained within the housing (1006) and actuates movement of a slidable elongated component (not shown). For the system adapted for implantation of ocular devices, the cannula (1012) and drive assembly (1014) have the same configuration as shown and described in Figures 3 and 4A to 4B, and therefore will not be described in detail here.

The delivery system (1000) also includes a fluid assembly (1016) within a handle (1002) (shown in FIG. 10B), the fluid assembly having a loading assembly (1018) configured to allow transfer of a fluid composition from an external source into a reservoir defined by the fluid assembly and a linear gear (1020). A slidable elongated member (1022) is coaxially disposed within a cannula lumen in fluid communication with the reservoir. As previously stated, in tool-based systems that do not deliver implants or fluids, the system may not include a reservoir.

In an exemplary method illustrated in Figures 11A to 11C, a fluid composition can be transferred to a reservoir (1102) of the system (1100) via loading assembly (1104). As shown, the reservoir (1102) is defined by a fluid assembly (1106) and a linear gear (1108). The linear gear (1108) has a proximal end (1110) and a distal end (1112), and an inner cavity (1114) extending from the proximal end (1110) to the distal end (1112). The inner cavity (1114) is in fluid communication with the inner cavity (not shown) of a slidable elongated member (1118). To deploy the fluid composition away from the reservoir (1102), the linear gear (1108) retracts in the direction of the arrow (Figure 11B), thereby pressurizing the reservoir (1102). Retraction can be achieved by rotation of a pinion mechanism (1120). Once sufficient pressure has been generated in the reservoir (1102), the fluid composition contained therein is injected into the Schlem tube through the inner cavity of the linear gear (1114) and the inner cavity of the elongated component (1118).

Here, any fluid flow delivered reaches the Schlemm tube via the distal end (1202). In other variations, the slidable elongated member (1300) may be configured to include a plurality of openings spaced apart along its axial length. The openings may have any suitable shape, such as slots (1302) (Fig. 13A) or circles (1304) (Fig. 13B). Fluid compositions delivered using the elongated members depicted in Figs. 13A and 13B may partially flow out of the elongated member through the openings and partially exit through the distal end of the elongated member. The distal end of the elongated member may also be configured as a half-tube (1306) (Fig. 13C).

Some variations of the fluid assembly include a locking mechanism for preventing movement of the assembly within the handle (e.g., when the linear gear is advancing or retracting). The locking mechanism may include a ratchet pawl, a ratchet pawl, or any other suitable combination of mechanisms, which can be locked to prevent movement of the fluid assembly and unlocked to allow movement of the fluid assembly.

Referring back to Figures 23A through 23F, another exemplary delivery system (2300) shown here for delivering a fluid composition into a Schlemm tube may include a housing (2334) and a sleeve (2344) extending from the distal end of the housing. A drive assembly (2202) (described above with respect to Figures 22A through 22D) may be positioned within the housing (2334), similar to a fluid assembly (2316) (described in more detail above). As described above, the drive assembly (2202) may include a linear gear (2204) and a pair of pinion mechanisms (2206) connected to a roller (2208). The delivery system (2300) may include a slidable elongated member (2336). The proximal end of the elongated member may be fixed relative to the linear gear (2204), while the distal end of the elongated member may be slidably and coaxially disposed within the cavity of the sleeve (2334). The fluid reservoir (2302) of the fluid assembly (2316) can be fluidly connected to the inner cavity of the elongated component. For example, including...

The plunger (2338) of the inner cavity can fluidly connect the reservoir (2302) to the inner cavity of the elongated component. The proximal end (2350) of the plunger (2338) can be slidably positioned within the reservoir (2302), and the distal end (2352) of the plunger can be fixedly attached to the linear gear (2204) of the drive assembly (2202).

The fluid assembly (2316) and the drive assembly (2202) may be connected via a link (2348), best shown in Figure 23D. (The delivery system (2300) in Figure 23A is shown without the link assembly to better illustrate the other components.) The link (2348) may be configured to allow the fluid assembly (2316) and the drive assembly (2202) to move as a whole, and may also allow for restriction of movement of the fluid assembly and the drive assembly relative to each other. In some variations, the link (2348) may allow the fluid assembly (2316) to move closer to rather than further away from the drive assembly (2202). For example, as best shown in Figure 23D, the proximal end (2340) of the link (2348) may be fixedly attached to the fluid assembly (2316). The distal end (2342) of the link (2348) can be attached to the linear gear (2204) of the drive assembly (2202) via a one-way ratchet. The distal end (2342) can move distally along a track in the linear gear (2204), but the teeth in the track can prevent the distal end (2342) from moving proximally along the track. Therefore, the fluid assembly (2316) can move toward the distal end of the linear gear (2204), bringing the fluid assembly and the linear gear closer together (via shortening of the portion of the link (2348) between the fluid assembly and the linear gear), but the fluid assembly may not be able to move away from the proximity of the linear gear. It should be understood that in other variations, the link can be fixedly attached to the linear gear and slidably attached to the fluid assembly.

Therefore, the linear gear (2204) and the fluid assembly (2316) are movable relative to each other and within the housing (2334). The movement of the linear gear (2204) and the fluid assembly (2316) relative to each other and relative to the housing (2334) can cause one or more effects, including extending and retracting the slidable elongated component and/or delivering the fluid composition. More specifically, since the proximal end (2350) of the plunger (2338) is slidably positioned within the reservoir (2302), and the distal end (2352) of the plunger is fixedly attached to the linear gear (2204), movement of the reservoir closer to the linear gear can cause proximal movement of the plunger within the reservoir. This can increase the length of the plunger (2338) positioned within the reservoir (2302). The portion of the plunger (2338) within the reservoir (2302) can displace fluid within the reservoir. The displaced fluid can be moved distally through the cavity of the plunger (2338), through the cavity of the elongated member (2336), and delivered outward through the distal opening of the cavity of the elongated member.

Additionally, as mentioned above, the movement of the linear gear (2204) relative to the housing (2334) allows the slidable elongated member (2336) to extend or retract. The linear gear (2204) can move between a proximal and distal position via the rotation of a roller (2208), which remains fixed relative to the housing (2334). Since the proximal end of the elongated member can be fixed relative to the linear gear (2204), and the distal end of the elongated member can slide within the cavity of the sleeve (2344), the elongated member can be correspondingly in a retracted position relative to the sleeve (2344) when the drive assembly (2202) is in the proximal position. When the elongated member is in the retracted position, the distal end of the elongated member can be positioned within the sleeve (2344) (e.g., near the distal tip of the sleeve). When the drive assembly (2202) is in the distal position, the elongated member can be in an extended position relative to the sleeve (2344). When the elongated member (2336) is in the extended position, the distal end of the elongated member can extend beyond the sleeve (e.g., distal to the distal tip of the sleeve).

The relative movement of the drive assembly (2202), the fluid assembly (2316), and the housing (2334) can thus be used to extend the slidable elongated member (2336) within the Schlemm tube and to retract the elongated member within the Schlemm tube while delivering fluid. The delivery system (2300) can be initiated in a configuration in which the fluid assembly (2316) and the linear gear (2204) are separated by the full distance of the link (2348), the fluid assembly being located at the proximal end of the housing (2334), and the slidable elongated member being in a retracted position within the sleeve (2344). This configuration is shown in Figures 23A through 23D. The roller (2208) can be rotated in a first direction to advance the linear gear (2204) distally within the housing (2334). The linkage (2348) allows the fluid assembly (2316) to move equidistantly within the housing, maintaining the distance between the fluid assembly and the linear gear (2204). As the linear gear (2204) advances, the elongated member (2336) can move from a retracted position to an extended position. This allows the elongated member (2336) to travel through the Schlemm tube. This configuration is shown in Figure 23F, which depicts a delivery system (2300) without the top of the housing (2334) to show the linear gear (2204) in the distal position. As can be seen here, the elongated member (2336) is in the extended position relative to the sleeve (2344), and the fluid assembly (2316) is also in the distal position within the housing (2334).

The roller (2208) can then be rotated in a second direction to retract the linear gear (2204) proximally within the housing (2334). This allows the slidable elongated member (2336) to move from an extended position to a retracted position. However, the fluid assembly (2316) may not move proximally within the housing (2334) accordingly. The housing (2334) may include internal teeth (2446) adjacent to the fluid assembly (2316) and configured to engage external teeth on the fluid assembly. These teeth may allow the fluid assembly (2316) to move distally within the housing (2334) rather than proximally. Thus, the fluid assembly (2316) may remain fixed relative to the housing when the linear gear (2204) retracts within the housing (2334). The linear gear (2204) and the fluid assembly (2316) can thus be moved closer together, with the connecting rod (2348) moving distally along a track in the linear gear (2204) to accommodate this movement. As the linear gear (2204) and the fluid assembly (2316) move closer together, the plunger (2338) can displace fluid in the reservoir (2302), as described in more detail above. The fluid can then travel through the cavity of the plunger (2338) and be delivered through the cavity of the elongated member (2336).

In this way, fluid can be delivered outside the elongated component simultaneously as it contracts. The fluid can replace the elongated component during contraction, and thus, fluid can be delivered to the Schlemm tube at the same angle and length as the elongated component's advance. For a given amount of contraction of the elongated component, a fixed, predetermined volume of fluid can be delivered because the fluid in the reservoir is displaced by the plunger, and both the contraction of the elongated component and the delivery of the fluid composition can be achieved by a single user movement (rotation of the roller (2208)). In some examples, complete contraction of the elongated component can result in the delivery of fluid between about 2 μl and about 9 μl. In some of these examples, complete contraction of the elongated component can result in the delivery of about 4.5 μl of fluid. The delivery system (2300) can incrementally produce an audible and/or tactile clicking sound as the elongated component (2336) contracts. For example, these clicking sounds can be attributed to the distal end (2342) of the connecting rod (2348) being driven by a ratchet relative to the distal end of the linear gear (2204). Each clicking sound can correspond to a fixed, predetermined volume of fluid, in some cases, about 0.5 μl.

In some variations, the delivery system may be configured to allow a slidable elongated component to extend and/or retract a fixed cumulative amount. The extension/retraction of the fixed cumulative amount may correspond to, for example, a full circumference of a Schlemm tube, two full circumferences of a Schlemm tube, or any desired distance. Exemplary fixed cumulative amounts may be (but are not limited to) about 39 mm to about 41 mm, about 38 mm to about 40 mm, about 35 mm to about 45 mm, about 78 mm to about 82 mm, about 76 mm to about 80 mm, or about 70 mm to about 90 mm. The delivery system may additionally or alternatively be configured to allow a fixed cumulative delivery of fluid (e.g., about 9 μl of fluid in some variations). For example, in the delivery system (2300), as described above, the fluid assembly (2316) may be able to move distally within the housing (2334) rather than proximally within the housing, and the fluid assembly may be able to move toward the linear gear (2204) rather than away from the linear gear. Therefore, with each extension of the slidable elongated component, the linear gear (2204) and the fluid assembly (2316) can move distally; but with each retraction of the elongated component, the linear gear can move proximally while the fluid assembly remains stationary. The delivery system (2300) may include a stop (e.g., a protrusion on the inner wall of the housing) that can prevent the fluid assembly (2316) from moving distally beyond a certain point. Once the fluid assembly (2316) has reached its distal position, neither the fluid assembly nor the linear gear (2204) can move distally or proximally, and the roller (2208) may cease to rotate. The distance between the initial position and its final distal position of the fluid assembly (2316) can indicate a fixed cumulative amount of extension/retraction of the slidable elongated component and a fixed cumulative delivery of fluid. However, it should be understood that other variations of the delivery system may not have a limited cumulative amount of extension and/or retraction of the elongated component; that is, some delivery systems may be able to repeatedly extend and retract without a fixed limit.

It should be understood that the delivery system (2300) may allow the slidable elongated component to advance and retract multiple times, provided the total cumulative amount is below a limit. In practice, in some variations, the maximum amount the elongated component can advance without retracting may be less than the total cumulative amount. For example, the elongated component may initially advance approximately halfway (i.e., 180 degrees, or approximately 19 mm to about 20 mm) around the Schlem tube in a first direction, which may be the maximum amount the elongated component can advance without retracting. The elongated component may then retract completely (fluid may be delivered during this period). After this initial extension, the fluid assembly (2316) may have moved half its maximum distance, and its distance to the linear gear (2204) may have decreased by approximately half of its total possible decrease. The delivery system (2300) may then rotate about the handle, and the elongated component may a second time advance approximately halfway around the Schlem tube in a second direction. The elongated component may then retract (fluid may be delivered during this period). At the end of the second extension, the fluid assembly (2316) may be positioned at its farthest point, and its distance to the linear gear (2204) may be at its minimum. At this point, the elongated component may no longer advance, no other fluid is available for delivery, and the roller may no longer rotate.

Device not configured to deliver fluid

It should be understood that not all delivery systems described herein are configured to deliver fluid compositions. Devices not configured to deliver fluid compositions may operate similarly to delivery systems configured to deliver fluid compositions, except that the retraction or advancement of the elongated component may not cause synchronous delivery of the fluid composition. In some examples, the delivery system may be identical to those configured to deliver fluid compositions, except that it may not contain a fluid composition. In other examples, the elongated component of a delivery system not configured to deliver fluid compositions need not include an internal cavity. Similarly, a delivery system not configured to deliver fluid compositions need not include a reservoir or plunger. The delivery system may include a solid occupant assembly having an external shape similar to the fluid assembly, instead of a reservoir. The occupant assembly may be connected via a linkage to a linear gear of the delivery system, which may or may not be integral with the occupant assembly. This allows many components to be interchangeable between delivery systems configured to deliver fluid compositions and those not configured to deliver fluid compositions, which simplifies manufacturing. Therefore, similar to a delivery system configured to deliver fluid, a system not configured to deliver fluid may or may not be configured to allow a fixed cumulative amount of extension and/or contraction, as described in more detail herein.

Some delivery systems not configured to deliver a fluid composition can be configured such that an elongated member ruptures a trabecular mesh. In some variations, the elongated member can be configured such that advancing and/or retracting the elongated member ruptures the trabecular mesh, and the elongated member can include one or more features to facilitate rupture of the trabecular mesh after advancing or retracting, such as a destructive component at the distal end of the elongated member, such as barbs, hooks, air bladders, etc. In other variations, the elongated member can be configured such that the body of the elongated member is configured to cut or tear the trabecular mesh. For example, the delivery system can be configured such that the elongated member can advance away from the cannula and around the Schlem tube; if the cannula is then removed from the eye without retracting the elongated member, the body of the elongated member can cut or tear the trabecular mesh upon removal from the cannula. The body of the elongated member can be configured to “pull open” the mesh, cutting or tearing it from a first positioning of the trabecular mesh near the tip of the cannula (i.e., at the proximal end of the elongated member), and continuing around the trabecular mesh toward the distal end of the elongated member. The elongated member can be configured to simultaneously apply a cutting or tearing force to the mesh at one location, sequentially around the Schlem tube, rather than applying a simultaneously cutting or tearing force to the mesh throughout the entire beam mesh being cut or torn.

Implantable eye device

The cannula of the system described herein can also deliver a variety of surgical instruments via an endoscopic approach. For example, catheters, sutures, probes, and other tools can be endoscopically inserted into the Schlemm canal and subsequently perforated, partially thickened, or partially perforated, either precisely positioned or entirely along the trabecular meshwork or the inner wall of the Schlemm canal. The surgeon can also advance the instruments entirely through the canal and through the outer wall of the collection canal into the sclera and subconjunctival space (again, entirely endoscopically) to create incisions targeting the scleral veins or subconjunctival space, which may drain aqueous humor into the scleral lake therein, or endoscopically deliver ocular devices that reside in the anterior chamber or Schlemm canal and drain into the scleral lake or subconjunctival space.

When the delivery system is used to implant an ocular device, the cannula may have a slidable positioning element coaxially disposed within the cannula lumen. The slidable positioning element typically includes an engagement mechanism for manipulating (e.g., releasably engaging, advancing, and/or retracting) the ocular device. Exemplary engagement mechanisms are depicted in Figures 5 through 9.

In Figure 5A, the engagement mechanism (500) includes a first jaw (502) and a second jaw (504). In its closed configuration (as shown in Figure 5A), the jaws (502, 504) are constrained within a sleeve (512) and hold an eye device (506) including a support (508) and at least one perforation (510). When the jaws (502, 504) advance away from the sleeve (512), they are no longer constrained and thus take on their open configuration, as shown in Figure 5B. The opening of the jaws (502, 504) releases the eye device (506) from the engagement mechanism (500). At least one tooth (514) may be provided in the first jaw (502), and at least one orifice (516) may be provided in the second jaw (504) to help secure the perforated eye device when the jaws are in their closed configuration. Figure 6 shows a variation of the engagement mechanism (600), in which the first jaw (602) and the second jaw (604) both include fangs (606) and orifices (608) to help grip the perforated eye device (610).

Referring to Figures 7A and 7B, other exemplary engagement mechanisms are depicted. In Figure 7A, the engagement mechanism (700) includes complementary mating elements. Specifically, the engagement mechanism (700) includes a concave element—a notch (702)—configured to engage with a complementary convex element (704), shown as a hook-shaped protrusion on the eye device (706). Here, the notch (702) may be fabricated at the end of a hypodermal cannula (708) (which will act as a positioning element). The concave element of the engagement mechanism (710) may include an opening (712) instead of a notch (702), as shown in Figure 7B, which engages with the convex element (704) on the eye device (706). In Figure 7B, the positioning element (714) may be fabricated from a wire or rod and the opening (712) produced via laser processing or other processes known in the art.

In other variations, the engagement mechanism can be configured as shown in Figures 8A and 8B. In those figures, the engagement mechanism (800) includes an annular portion (802). It can be advantageous to use this particular engagement mechanism with an eyepiece (804) comprising a latch (806) having an arm or earpiece (808) having a closed configuration and an extended configuration. Similar to the variations shown in Figures 5A and 5B, the earpiece (808) is restrained within the sleeve (810) in its closed configuration before advancing away from the sleeve (810). In its restrained configuration, the earpiece (808) engages with the annular portion (802) of the engagement mechanism (800) to prevent release of the eyepiece (804) from the system. When the annular portion (802) of the engagement mechanism (800) advances sufficiently so that the ear piece (808) is no longer constrained by the sleeve (810), the ear piece (808) presents its unfolded configuration, thereby releasing the eye device (804) from the annular portion (802) and entering the Schlemm tube, as shown in FIG8B.

Figure 9 shows another exemplary engagement mechanism (900) including a coiled portion (902) and a hook (904). When an eye device (906) having at least one perforation (908) (e.g., a proximal perforation) is implanted, the hook (904) can be releasably engaged with the perforation (908). The eye device (906) can be disengaged from the hook by applying a gentle force to the coil (902) or by another component (not shown) that may advance over the coil (902) to push the device (906) away from the hook (904). It may be advantageous to use the hook (904) when it is desired to retract the eye device (906).

The ocular delivery system may further include a slidable positioning element coaxially disposed within the lumen of the cannula for controlled implantation of an ocular device within the Schlem canal. The positioning element typically includes a proximal, distal, and distal engagement mechanism. The ocular device is typically releasably attached to the engagement mechanism. The positioning element may advance to deploy the ocular device within the cannula into the Schlem canal, or it may retract to facilitate positioning and/or repositioning of the ocular device, or disengagement of the ocular device from the engagement mechanism.

Some variations of the engagement mechanism include a proximal coiled portion and a distal hook. When implanting an implant with at least one perforation (e.g., a proximal perforation), the hook can be releasably engaged with the perforation. The ocular device can be disengaged from the hook by applying gentle force to the coil, by advancing it over the coil to push the device away from the hook by another component, or by using a shape-memory material that passively detaches upon exiting the cannula. It may be advantageous to use the hook when it is desired to retract the ocular device. The surgeon can move only the delivery system and the engagement mechanism to disengage it from any perforation or notch on the implant.

In another variation, the engagement mechanism includes opposing jaws. Here, the engagement mechanism may include a first jaw and a second jaw, wherein the jaws have a closed configuration and an open configuration. The jaws are used to grasp and manipulate the eye device and to releasably connect the eye device to a positioning element. The jaws can be formed by splitting or forking the distal end of a wire (e.g., by laser cutting). The gripping force of the jaws can be achieved by confining the jaws within a sleeve. The eye device can be released after the jaws advance away from the sleeve and unfold. The jaws can also be pivotally connected. In yet another variation, the first jaw may include at least one tooth, and the second jaw may include at least one aperture for receiving the tooth when the jaws are in the closed configuration.

In other variations, the engagement mechanism includes an annular portion. This variation of the engagement mechanism is typically used with eye devices that include a spring-loaded latch at its proximal end, wherein the latch has a compression configuration and an unfolded configuration. The latch is typically manufactured in the unfolded position. Thus, when the device with the latch is placed within the sleeve, the first and second arms or lugs of the latch can be compressed around the annular portion of the engagement mechanism. Once the clamping portion of the device has disengaged from the sleeve, the arms or lugs can unfold to release the eye device from the annular portion.

Another variation of the engagement mechanism includes a concave-convex interface. For example, the engagement mechanism may include a notch configured to engage with a complementary mating element (e.g., an ear) on the ocular device. The notch (concave component) may be formed within a subcutaneous cannula or may be formed by creating a perforation through the distal end of a positioning element made of solid wire or material, and the ear or hook (convex component) may be formed as part of the ocular device and may be inserted into the perforation or notch in the positioning element. Using this configuration, the ocular device can be released from the positioning element as it advances away from the cannula via surgical manipulation or by the shape of the positioning element, or both, such that the shape passively detaches the positioning element from the ocular device.

II. Reagent Kit

The delivery system described herein can be housed in a dedicated package. The package may be designed to protect the system, and more specifically, the sleeve. The package may need to prevent contact between the distal tip of the sleeve and any other object or surface. For this purpose, the package may include one or more elements configured to secure the delivery system to one or more locations near the distal tip of the sleeve. Secure the delivery system to at least two locations near the distal tip of the sleeve may be desirable, thereby limiting the ability of the delivery system to pivot relative to the package.

In one exemplary variation, the package may include a tray including a notch shaped generally corresponding to the shape of the delivery system and including one or more clamps configured to secure the delivery system in a position near the sleeve. Figure 26A illustrates an exemplary tray (2604) for the delivery system (2600). The tray (2604) may include a notch (2606) configured to receive the delivery system (2600). The tray (2604) may include first (2608) and second (2610) distal clamps and first (2612) and second (2614) proximal clamps configured to secure the delivery system (2600) within the notch (2606). When the delivery system (2600) is secured within the tray (2604), the sleeve (2602) of the delivery system may be suspended such that the sleeve does not contact the tray, and the clamps may restrict the pivoting of the delivery system (2600) in a manner that would allow the sleeve (2602) to contact the tray. The grips can be configured to securely hold the delivery system (2600) within the tray (2604) while also allowing the user to remove the delivery system from the tray in a controlled manner. The kits described herein include variations of additional components, which can be packaged to accommodate. For example, Figure 26B shows an exemplary tray (2626) including a notch (2628) configured to accommodate a loading tool (2624) and a delivery system (2620). As shown in Figure 26C, the tray (2640) can be configured to be sealed (e.g., heat-sealed) with a cap (2642) and located within a box (2644). The box (2644) may optionally further contain instructions for use (2646). The cap (2642) and/or the box (2644) may optionally have a label (2648) affixed thereto.

It should be understood that the package may have other configurations that protect the distal tip of the sleeve. For example, in another variation, the package may include a rigid planar sheet to which the delivery system may be attached in one orientation such that the sleeve does not contact the planar sheet. The delivery system may be attached along the housing (e.g., via tape or other material wound around the housing) at two or more points to prevent movement of the delivery system relative to the planar sheet. It may be necessary to protect the sleeve on at least two sides; for example, the portion of the planar sheet near the sleeve may be bent around the sleeve to protect the sleeve on at least two sides, or a second rigid planar sheet may be attached to the delivery system opposite to the first planar sheet.

Some kits described herein may include multiple delivery systems. For example, a kit may include two delivery systems. In some variations, a kit may include two identical systems, such that, for example, a first delivery system can be used for a patient's first eye, and a second delivery system can be used for a patient's second eye. In other variations, a kit may include two different systems. For example, the first delivery system may be configured to deliver a fluid composition, and the second delivery system may not be configured to deliver a fluid composition, but may actually be configured to use elongated components to rupture the trabecular meshwork. Kits including multiple systems may be packaged in any suitable manner. For example, Figure 27A shows a kit including two delivery systems (2700, 2702) in a stacked configuration (shown without an outer package), and Figure 27B shows a kit including two delivery systems (2704, 2706) in a side-by-side configuration (shown without an outer package). Similarly, the delivery systems (2700, 2702) can be configured to deliver a fluid composition, can be configured not to deliver a fluid composition (e.g., can be configured to deliver an elongated member to cause the trabecular mesh to break), or one can be configured to deliver a fluid composition and the other can be not configured to deliver a fluid composition. Likewise, the delivery systems (2704, 2706) can be configured to deliver a fluid composition, can be configured not to deliver a fluid composition, or one can be configured to deliver a fluid composition and the other can be not configured to deliver a fluid composition.

Some kits may include ocular implants other than one or more delivery systems as described herein. For example, a kit may include one or more devices configured for implantation into a Schlem tube, which are typically configured to keep the Schlem tube open without substantially interfering with transmural fluid flow through the tube. The kit may include one or more ocular implants, such as (but not limited to) vascular stents for placing a Schlem tube. In some variations, the ocular implant may be one or more of those disclosed in U.S. Patent No. 7,909,789 and U.S. Patent No. 8,529,622, previously incorporated herein by reference in their entirety. In one variation, the device may include a twisted band member comprising a double helix structure including a first elongated edge and a second elongated edge and a plurality of struts extending between the elongated edges in a direction substantially perpendicular to the central longitudinal axis of the twisted band member. The struts may define a plurality of perforations spaced apart along at least a portion of the length of the twisted band member.

III. Methods

Methods for treating ocular conditions and/or for implanting ocular devices using the systems described above, delivering fluid compositions into the Schlem tube, and/or delivering tools into the Schlem tube are also provided. In some instances, treating an ocular condition can cause an increase in aqueous humor outflow, a decrease in resistance to aqueous humor outflow, and/or a decrease in intraocular pressure. Some methods described herein can dilate the Schlem tube, dilate the collecting tube, and/or rupture any collagenous septa that may impede circumferential flow through the Schlem tube. Dilation of the Schlem tube may rupture the obstructed inner wall of the tube, stretch the trabecular meshwork, and/or increase the porosity of the trabecular meshwork. This can improve the natural aqueous humor outflow path. Dilation can be performed by advancing a tool (e.g., a sliding elongated component as described herein). Alternatively or additionally, dilation can be performed by delivering a fluid composition (e.g., a viscoelastic fluid as described herein). Alternatively or additionally, some methods described herein may include performing trabeculotomy to cut the trabecular meshwork. Alternatively or concurrently, some of the methods described herein may include implanting an ocular device into a Schlemm canal. In some instances, the systems described herein may be used to perform internal trabeculotomy, internal transluminal trabeculotomy, clear keratotomy, clear transluminal trabeculotomy, internal canal reshaping, and/or clear canal reshaping. In some instances, the delivery system may also be used for dissolving anterior chamber adhesions, viscogonioplasty, assisting with intraocular lens exchange, suspending a descending lens or foreign body, and/or repositioning prolapsed iris tissue.

The method is typically a single-handed, single-operator controlled approach that is minimally invasive, for example, adapted for internal approaches, as previously mentioned, where it may be superior to the more invasive external approaches. However, the use of ocular systems via external approaches may be anticipated in some cases, and therefore, the use of such ocular systems is not excluded herein. Methods for delivering ocular devices or fluids, or for providing destructive force, may be used to treat or prevent glaucoma, early-stage glaucoma, or high intraocular pressure. When treating glaucoma, the method may also be used in conjunction with (before or after) cataract surgery performed at the same stage or at another time using the same incision.

Some of the methods described in more detail below may include using the delivery system described herein to dilate the Schlem's canal and/or aqueous humor collecting duct (e.g., with a viscoelastic fluid). Other methods, also described in more detail below, may include tearing or cutting the trabecular meshwork of the Schlem's canal. These methods may be performed individually or may be combined in a single procedure. For example, in some cases, a portion (e.g., half) of the Schlem's canal may be dilated (e.g., using a fluid composition or tool, or both), and the same or different portions of the trabecular meshwork of the Schlem's canal within the same eye may be torn or cut. As another example, the entire Schlem's canal may be dilated, and subsequently all or part of the trabecular meshwork may be torn or cut. For example, this may be desirable in order to both dilate the collecting duct and tear or cut the trabecular meshwork.

In some of these variations, expansion and tearing or cutting can be performed using a single delivery system, such as a delivery system configured to deliver a fluid composition as described herein. For example, an elongated component configured to deliver a fluid composition may first be used to deliver the fluid composition to a portion of a Schlem tube (e.g., approximately 180 degrees of curvature of the tube, approximately 90 degrees of curvature of the tube) as described herein, and subsequently to tear or cut the braided mesh in the same portion of the tube as described herein. As another example, an elongated component configured to deliver a fluid composition may first be used to deliver the fluid composition to a portion of a Schlem tube (e.g., approximately 180 degrees of curvature of the tube, approximately 90 degrees of curvature of the tube, etc.), and subsequently to tear or cut the braided mesh in another portion of the tube (e.g., another approximately 180 degrees of curvature, another 90 degrees of curvature, etc.). As another example, the elongated component of a delivery system configured to deliver a fluid composition can first be used to deliver the fluid composition to all the Schlem tubes (e.g., by delivering the fluid composition at about 180 degrees in a first direction and then by delivering the fluid composition at about 180 degrees in a second direction), and then be used to tear or cut the entire 360-degree beam mesh (e.g., by tearing or cutting the beam mesh at about 180 degrees in a first direction and then tearing or cutting the beam mesh at about 180 degrees in a second direction).

In other variations, dilation and tearing or cutting can be performed using different delivery systems (e.g., dilation can be performed using a delivery system configured to deliver a fluid composition, and tearing or cutting can be performed using a delivery system not configured to deliver a fluid). As yet another example, in some cases, dilation can be performed in one of the patient's eyes while tearing or cutting the trabecular meshwork in the patient's other eye.

In the same patient, in the same eye or different eyes, procedures involving dilation of the Schlem canal and/or tearing or cutting of the trabecular meshwork can be combined with procedures for delivering an ocular device (described in more detail here). For example, all or part of the Schlem canal may be dilated, followed by insertion of an ocular device. As another example, a portion of the trabecular meshwork may be torn or cut, and an ocular implant may be delivered to another portion of the Schlem canal. As yet another example, a portion of the Schlem canal may be dilated, and an ocular implant may be delivered to another portion of the Schlem canal. As yet another example, an ocular implant may be delivered to a portion of the Schlem canal, and the Schlem canal may then be dilated to improve the function of the ocular implant.

Eye device delivery

Generally, methods for implanting an ocular device within a Schlem cannula first involve creating an incision in the eye wall (e.g., the sclera or cornea or limbus or junction) that provides access to the anterior chamber of the eye. As shown in the stylized description of the eye in Figure 14, the cannula (1400) of the ocular delivery system then advances through the incision and at least partially through the anterior chamber (1402) to reach the trabecular meshwork (not shown). The Schlem tube (i.e., the lumen (1404) of the Schlem tube) then enters through a distal bend of a cannula (1406), and a slidable positioning element (or, for example, a slidable tool or guide), or an elongated component (generally indicated by element 1408) advances from the cannula to implant an ocular device within the Schlem tube, perform surgery within the Schlem tube or in adjacent trabecular canal tissue, or deliver fluid into the tube. However, in some examples, the elongated component may not be used to allow any fluid to be delivered to be delivered through the cannula. In yet other variations, only the trabecular meshwork is punctured and the fluid composition is delivered without circumferentially around the Schlem tube.

As previously stated, in some variations, the cannula may be configured to include proximal and distal curved portions, wherein the distal curved portion has a proximal end, a distal end, and a radius of curvature defined between said ends. Here, the cannula may also include a body and a distal tip having a bevel directly engaging the radius of curvature, for example, said bevel being adjacent to the radius of curvature. In other variations, the Schlemm cannula may be inserted using a straight cannula (i.e., a cannula without the distal curved portion). The method may also include steps of flushing the system with fluid (e.g., removing air from the system) and/or flushing the surgical area to remove blood or to further improve imaging of said area.

Any suitable ocular device that maintains the openness of the Schlemm tube or improves the outflow of aqueous humor can be implanted using the system described herein. For example, an ocular device that maintains the openness of the Schlemm tube without substantially interfering with the flow of fluid through, along, or out of the tube can be implanted. Such devices may include a support with at least one perforation, as disclosed in U.S. Patent Nos. 7,909,789 and 8,529,622, which are previously incorporated herein by reference in their entirety. Ocular devices that rupture the adjacent inner wall of the trabecular meshwork or Schlemm tube can also be implanted. In addition to ocular devices made of metal or metal alloys, ocular devices using sutures, modified sutures, modified polymers, polymer filaments, or solid viscoelastic structures can be delivered. Fluid compositions, such as saline, viscoelastic fluids, air, drug mixtures or solutions, and gases, can also be delivered.

When delivering a fluid composition into a Schlem cannula, the method typically includes the following steps: creating an incision in the eye wall (e.g., the sclera or cornea) to provide access to the anterior chamber of the eye; advancing a cannula of the ocular delivery system through the incision and at least partially through the anterior chamber to reach the trabecular meshwork; inserting the cannula into the Schlem cannula; and delivering the fluid composition into the cannula using an elongated member that can slide within the lumen of the cannula. The cannula may be configured to include proximal and distal curved portions, wherein the distal curved portion has a proximal end and a distal end, and a radius of curvature defined between the ends. Here, the cannula may also include a body and a distal tip having a bevel that directly engages the radius of curvature, for example, the bevel being adjacent to the radius of curvature. Other advantageous cannula features described above may also be included. The method may also include the steps of flushing the system with fluid (e.g., removing air from the system) and/or flushing the surgical area to remove blood or to further improve imaging of the area.

When the internal approach is used for implanting an ocular device, the method may include the following steps. The surgeon may first examine the anterior chamber and trabecular meshwork (with the underlying Schlemm canal) using a surgical microscope and gonioscope or gonioscope. Using a 0.5 mm or larger corneal, limbal, or scleral incision, the surgeon may then gain access to the anterior chamber. A saline solution or viscoelastic composition may then be introduced into the anterior chamber to prevent collapse. Here, the saline solution or viscoelastic composition may be delivered via a delivery system cannula or via another mode, such as infusion through a flushing sleeve on the cannula. Under direct microscopy, the surgeon may then advance the delivery system cannula through the incision toward the anterior chamber angle. Upon approaching the angle (and thus the trabecular meshwork), the surgeon may apply a gonioscope or gonioscope to the cornea to visualize the angle. Applying a fluid (e.g., a viscous solution or a viscoelastic composition as previously described) to the cornea and/or the gonioscope or gonioscope can facilitate good optical contact and counteract total internal reflections, thereby allowing imaging of the anterior chamber angle. As the surgeon observes the trabecular meshwork, the cannula can then be advanced such that the bevel at the distal end of the distal curved portion of the cannula pierces the meshwork and communicates with the lumen of the Schlem canal. The surgeon can flush the cannula or the anterior chamber with saline or a viscoelastic composition to prevent chamber collapse, dilate the Schlem canal, or wash away any blood that could obscure the imaging delivered by the cannula and ocular device. The ocular device is then released from the engagement mechanism as desired by the surgeon, allowing it to remain within the Schlem canal. If repositioning of the ocular device is required or desired, the surgeon can retract the device and/or change its position using the positioning elements of the delivery system. The surgeon can then remove the delivery system from the eye.

Other variations of the endoscopic approach for implanting ocular devices include the use of an endoscope. Similar to the method described above, access to the anterior chamber is first obtained by incising the cornea, limbus, or sclera. This can also be performed in combination with cataract surgery (before or after) in a pre-set mode or independently. The anterior chamber may be infused with saline solution, or a viscoelastic composition may be placed in the anterior chamber to prevent collapse. Saline or viscoelastic agents can be delivered as a separate step, or they can be infused using a slender part of the delivery system, a slender part, or a flushing sleeve on the cannula, or a separate infusion cannula. Under direct microscopy, the surgeon then advances the endoscope through the incision toward the horn and trabecular meshwork. As the surgeon views the trabecular meshwork using the endoscope or any associated video monitor, the beveled end of the cannula advances to pierce the meshwork. The ocular device is then advanced using positioning elements under endoscopic imaging. The surgeon can flush the tube or the anterior chamber with saline or a viscoelastic composition to prevent chamber collapse, dilate the Schlem tube, or wash away any blood that could obscure the imaging delivered by the cannula and ocular device. When the ocular device has advanced to the surgeon's desired extent, it is released from the engagement mechanism to allow it to remain in the Schlem tube. If repositioning of the ocular device is required or desired, the surgeon can use the positioning elements of the delivery system to retract and/or advance the device. The surgeon can then remove the delivery system from the eye.

Fluid composition delivery

Some methods described herein may include delivering a fluid composition into the eye, such as into the Schlem canal. In some methods, an elongated member including a lumen may be inserted into the Schlem canal, and the fluid composition may be delivered via the elongated member. Both the elongated member and the fluid delivery can expand the Schlem canal, and the fluid delivery can additionally expand the collection tube. The delivery of the fluid composition is similar to that used in implantation of ocular devices. However, the delivery system may employ a slidable elongated member to infuse the fluid composition into the Schlem canal, rather than using a positioning element.

The fluid composition can be delivered to expand a Schlem tube. The entire length of the Schlem tube or a portion thereof can be expanded by the fluid. For example, at least 75%, at least 50%, at least 25%, at least 10%, or at least 1% of the tube can be expanded. The fluid composition can also be delivered to treat a variety of medical conditions of the eye, including (but not limited to): glaucoma, early glaucoma, anterior or posterior segment angiogenesis, anterior or posterior segment inflammatory disease, ocular hypertension, uveitis, age-related macular degeneration, diabetic retinopathy, hereditary eye conditions, complications of cataract surgery, vascular occlusion, vascular disease, or inflammatory disease.

The surgeon can first examine the anterior chamber and trabecular meshwork (with the underlying Schlemm canal) using a surgical microscope and gonioscope or gonioscope. Using a 0.5 mm or larger corneal, limbal, or scleral incision, the surgeon can then gain access to the anterior chamber. A saline solution or viscoelastic composition can then be introduced into the anterior chamber to prevent collapse. Here, the saline solution or viscoelastic composition can be delivered via a delivery system cannula or via another mode, such as infusion through a flushing sleeve on the cannula. Under direct microscopy, the surgeon can then advance the delivery system cannula through the incision toward the anterior chamber angle. Upon approaching the angle (and thus the trabecular meshwork), the surgeon can apply a gonioscope or gonioscope to the cornea to visualize it. Applying a viscous fluid (e.g., a viscoelastic composition as previously described) to the cornea and/or the gonioscope or gonioscope can facilitate good optical contact and counteract total internal reflections, thereby allowing imaging of the anterior chamber angle. As the surgeon observes the trabecular mesh, the cannula can then be advanced such that the bevel at the distal end of the curved distal portion of the cannula pierces the mesh and communicates with the lumen of the Schlemm cannula.

Next, under gonioscopy, a slidable elongated component coaxially positioned within the cannula's lumen can enter the cannula. The elongated component can advance around the cannula by any suitable amount and direction. For example, the elongated component can advance around the cannula between approximately 1 degree and approximately 360 degrees, between approximately 10 degrees and approximately 360 degrees, between approximately 150 degrees and approximately 210 degrees, or any suitable distance, around the cannula approximately 360 degrees, around the cannula approximately 270 degrees, around the cannula approximately 180 degrees, around the cannula approximately 120 degrees, around the cannula approximately 90 degrees, around the cannula approximately 60 degrees, around the cannula approximately 30 degrees, or around the cannula approximately 5 degrees. In some variations, the elongated component can advance in two steps, for example, first in a clockwise direction (e.g., about 180 degrees, about 90 degrees, etc.) and then in a counterclockwise direction (e.g., about 180 degrees, about 90 degrees, etc.) around the tube (e.g., thus achieving 360-degree or 180-degree internal viscoelastic cannulation or cannulation reshaping). Fluid can be injected after the elongated component advances or contracts. Once the slidable elongated component has been positioned within the tube, a fluid composition (e.g., a viscoelastic solution) can be delivered continuously or intermittently through the lumen of the elongated component. The fluid composition can exit the lumen of the elongated component through its distal end (e.g., through the distal tip), or through an opening or perforation provided along its axis, or a combination of both. The openings or perforations can be spaced apart along the axial length of the elongated component in any suitable manner, for example, symmetrically or asymmetrically spaced along its length. Other substances, such as drugs, air, or gases, can be delivered in the same manner if necessary.

In some variations, the slidable elongated component can be repositioned by contraction or repeated advance and contraction. In some variations of the method, the same or different incisions can be used; however, the delivery system cannula is used to enter and expand the Schlem tube from a different direction (e.g., counterclockwise instead of clockwise). Once a sufficient amount of fluid has been delivered, the surgeon can retract the slidable elongated component into the cannula and remove the delivery system from the eye. It should be understood that the cannula described herein can be specifically manufactured to include a dual-surface configuration (i.e., steep and smooth surfaces) at the distal tip, which can allow the elongated component to advance, reposition, and/or retract without severing it at the distal tip of the cannula. It should also be understood that these steps can be used alone or in combination with cataract surgery (in one set mode).

Some of the delivery systems described herein can be configured to limit the cumulative amount of forward and/or retraction of the slidable elongated component. For example, as described above, after a certain cumulative distance of forward and retraction of the elongated component (e.g., approximately 39 mm to approximately 40 mm for each forward and retraction, corresponding to approximately the circumference of a Schlemm tube; or approximately 78 mm to approximately 80 mm for each forward and retraction, corresponding to approximately twice the circumference of a Schlemm tube; or any other suitable distance), it can no longer advance. This forward and retraction may occur over multiple forward-retraction cycles. For example, the elongated component may advance approximately 20 mm, then retract approximately 20 mm, then advance approximately 20 mm, then retract approximately 20 mm. When the cumulative distance is limited to approximately 40 mm, after these two forward and retraction cycles, the elongated component can no longer advance.

In some variations of the internal delivery method, the fluid composition can be delivered simultaneously with the contraction of the elongated component (i.e., the fluid composition can be delivered in a manner that allows fluid to advance beyond the system cannula due to the contraction of the system components). Referring again to Figures 11A through 11C, the linear gear (1108) contracts in the direction of the arrow (Figure 11B), thereby pressurizing the reservoir (1102). Contraction can be achieved by rotation of the pinion mechanism (1120). Once sufficient pressure has been generated in the reservoir (1102), the fluid composition contained therein is injected into the Schlemm tube through the linear gear cavity (1114) and the elongated component (1118). It should be understood that the ocular delivery system can be configured to deliver the fluid composition continuously, passively, automatically, or actively by the surgeon. The fluid composition can also be delivered to the tube independently of the movement of the gear shaft using a pump or auxiliary plunger. In some variations, the contraction of the elongated component can correspond to the delivery of a fixed volume of fluid composition via the cavity of the elongated component. The fluid composition can be delivered via a distal opening in the lumen of the elongated component as it contracts, and thus the fluid can be delivered uniformly throughout the entire portion of the tube through which the elongated component advances.

Fluid compositions that can be delivered via the ocular system described herein may include, but are not limited to, physiological saline and viscoelastic fluids. Viscoelastic fluids may include hyaluronic acid, chondroitin sulfate, cellulose, or salts, derivatives of, or mixtures thereof, or solutions thereof. In one variation, the viscoelastic fluid includes sodium hyaluronate. In another variation, the viscoelastic composition may further include a drug. For example, the viscoelastic composition may contain a drug suitable for treating glaucoma, reducing or lowering intraocular pressure, reducing inflammation, fibrosis, angiogenesis, or scarring, and/or preventing infection. The viscoelastic composition may also contain agents that aid in the imaging of the viscoelastic composition. For example, it may include dyes such as (but not limited to) fluorescein, trypan blue, or indigo green. In some variations, fluorescent or bioluminescent compounds are included in the viscoelastic composition to aid in its imaging. In other variations, the system delivers the drug alone, without delivering the viscoelastic composition. In this case, the drug may be loaded onto or within a continuously releasing biodegradable polymer that dissolves the drug over a period of weeks, months, or years. It is also anticipated that the system can be used to deliver air or gas, as described herein.

Other variations of the endoscopic approach for delivering the fluid composition include the use of an endoscope. Similar to the method directly described above, access to the anterior chamber is first obtained by incising the cornea, limbus, or sclera. This can also be performed in combination with cataract surgery (before or after) in a set mode or independently. The anterior chamber may be infused with saline solution, or a viscoelastic composition may be placed in the anterior chamber to prevent collapse. Saline or viscoelastic can be delivered as a separate step, or it can be infused using an elongated part of the delivery system, an irrigation sleeve on the elongated part or cannula, or a separate infusion cannula. Under direct microscopy, the surgeon then advances the endoscope through the incision toward the horn and trabecular meshwork. As the surgeon views the trabecular meshwork via the endoscope or any associated monitor, the beveled end of the cannula advances to pierce the meshwork. The elongated part then advances under endoscopic imaging. The elongated part can advance around the cannula by any suitable amount and direction. For example, the elongated component can advance around the tube at a distance of approximately 10 degrees to approximately 360 degrees, or it can advance in two steps, for example, 180 degrees clockwise and 180 degrees counterclockwise (thus achieving a complete 360-degree internal viscoelastic cannulation). Once the elongated component is positioned within the tube, a fluid composition (e.g., a viscoelastic fluid) can be delivered continuously or intermittently through the lumen of the elongated component. The fluid composition can exit the lumen of the elongated component through its distal end (e.g., through the distal tip), or through an opening or perforation provided along its axis, or a combination of both. The opening or perforation can be spaced along the axial length of the elongated component in any suitable manner, for example, symmetrically or asymmetrically spaced along its length. Other substances, such as drugs, air, or gases, can be delivered in the same manner if necessary. The elongated component can be repositioned by contraction or repeated advance and contraction. In some variations of the method, the same or different incisions may be used; however, the delivery system cannula is used to enter and dilate the Schlem canal from a different direction (e.g., counterclockwise instead of clockwise). Once a sufficient amount of fluid has been delivered, the surgeon can retract the slidable elongated component into the cannula and remove the delivery system from the eye. A variation of the method described herein is illustrated in Figures 28A through 28D and can be performed using the delivery system as described with respect to Figures 23A through 23F. Figure 28A shows a flowchart illustrating the method. The method shown herein allows for single-handed, manual manipulation of fluid (e.g., viscoelastic fluid or gel) into the Schlem canal via a slidable elongated component including an endoscope (e.g., a microcatheter). The delivery of the viscoelastic fluid can be metered, allowing for controlled, small-volume delivery of the viscoelastic agent to the eye. The method can use a single clear corneal incision for entry to allow for 360-degree cannula insertion and transluminal viscoelastic dilation of the Schlem canal. For example, this can lower intraocular pressure in patients with glaucoma (e.g., open-angle glaucoma).

First, the delivery system can be removed from its packaging. Next, the delivery system can be pre-loaded with viscoelastic fluid. A loading tool (e.g., a nozzle) for the delivery system, which is supplied with the kit, can be attached to the viscoelastic cartridge. Suitable commercially available viscoelastic agents include, but are not limited to, Healon ^™ , HealonGV ^™ , Amvisc ^™ , and PROVISC ^™ . The loading tool can then be rinsed with the viscoelastic agent. The lock on the proximal end of the delivery system can then be rotated (while retaining the handle attached to the device) to expose the proximal opening in the device. The nozzle can then be inserted into the proximal opening and into the viscoelastic fluid injected from the viscoelastic cartridge into the reservoir of the delivery system. It may be necessary to keep the delivery system and viscoelastic cartridge upright during injection. Viscoelastic fluid can be injected until a viscoelastic flow from the distal tip of the cannula is observed. The lock can then be removed from the delivery system.

To deliver viscoelastic fluid into the eye, a cannula can be inserted into the anterior chamber through an existing corneal or scleral incision. An incision of at least approximately 1 mm width may be required. The distal tip of the cannula can be used to pierce the trabecular meshwork to access the Schlem's canal. As the elongated component enters the Schlem's canal, the cannula can be firmly held against the angle. One or more exposed portions of the rollers driving the assembly can be rotated proximally to advance the elongated component up to approximately 180 degrees around the Schlem's canal (approximately 18 mm, 19 mm, 20 mm, 18 mm to 20 mm, or 15 mm to 25 mm of circumferential tubular travel). At this point, the elongated component can be fully extended, and the rollers can no longer rotate. During this procedure, direct microscopy or gonioscopy of the cannula tip can be maintained, and the anterior chamber can be maintained by viscoelastic or continuous balanced saline infusion.

One or more rollers may then be rotated distally to cause the elongated component to contract. As the elongated component contracts, a predetermined volume of viscoelastic agent may be metered and continuously delivered outside the lumen of the elongated component, which may cause transluminal viscoelastic expansion of the Schlem tube and/or collection tube. In some variations, complete contraction of the elongated component results in the delivery of between about 2 μl and about 9 μl of viscoelastic fluid (e.g., about 4.5 μl of viscoelastic fluid). The rollers may be configured to rotate incrementally with audible and/or tactile clicks; in some cases, about 0.5 μl of viscoelastic fluid may be delivered with each click. Figures 28B to 28D illustrate the delivery of viscoelastic agent (2800) to the Schlem tube (2802) and collection tube (2804) during the contraction of the elongated component (2806) into the sleeve (2808). As can be seen in Figures 28C to 28D, the angle and length of delivery of the viscoelastic agent (2800) to the Schlemm tube correspond to the angle and length of the elongated component entering the tube. In some cases, the viscoelastic agent can be used to plug any blood return to the anterior chamber.

The viscoelastic fluid can then optionally be delivered to the other half of the Schlem canal. The cannula tip can be removed from the Schlem canal, and the delivery system can be flipped so that the cannula tip rotates 180 degrees to face the opposite direction. In some cases, the delivery system can be flipped in the anterior chamber without removing the cannula from the eye. In other cases, the delivery system can be removed from the eye, flipped, and reinserted into the incision. The cannula tip can then be reinserted into the Schlem canal through the same incision in the trabecular meshwork, and the advance, contraction, and viscoelastic fluid delivery as described above can be repeated to viscoelastically expand the remaining 180 degrees of the Schlem canal. The complete procedure delivers between approximately 4 μl and approximately 18 μl of viscoelastic fluid (e.g., approximately 9 μl of viscoelastic fluid) entirely to the eye.

At the end of the procedure, the anterior chamber can be flushed through the corneal wound (e.g., with a balanced salt solution) (manually or automatically). If necessary, a balanced salt solution or viscoelastic agent can be used to reform the anterior chamber to achieve physiological pressure and further impede any blood return from the collection tube into the anterior chamber. If necessary, sutures can be used to seal the corneal or scleral incision. Postoperatively, antibiotics or antiseptics, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for weeks or months to help prevent adhesions and corneal closure.

More generally, in the methods described herein, exemplary volumes of viscoelastic fluid that can be delivered may be between about 1 μl and about 200 μl in some examples, or between about 1 μl and about 100 μl in others. In some examples, volumes sufficient to provide destructive force may range from about 1 μl to about 50 μl, from about 1 μl to about 30 μl, or from about 2 μl to about 16 μl. In one variation, a volume of about 4 μl is sufficient to rupture the Schlemm tube and/or surrounding tissue. In other variations, the volume of viscoelastic fluid sufficient to rupture trabecular tubule tissue can be about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl, about 11 μl, about 12 μl, about 13 μl, about 14 μl, about 15 μl, about 16 μl, about 17 μl, about 18 μl, about 19 μl, about 20 μl, about 25 μl, about 30 μl, about 35 μl, about 40 μl, about 45 μl, or about 50 μl.

Tissue rupture can occur through excessive and intentional viscoelastic expansion using at least about 1 μl, about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl, about 11 μl, about 12 μl, about 13 μl, about 14 μl, about 15 μl, about 16 μl, about 17 μl, about 18 μl, about 19 μl, or about 20 μl of viscoelastic fluid per 360-degree arc of the tube. In some variations, at least about 20 μl, about 25 μl, about 30 μl, about 35 μl, about 40 μl, about 45 μl, or about 50 μl of viscoelastic fluid may be delivered.

Depending on factors such as the type or severity of the condition being treated, destructive forces can be generated to partially or completely destroy and/or remove the trabecular mesh, and can be adjusted by changing the volume of the delivered viscoelastic fluid. For example, 8 μl can be used to perforate or gently tear the mesh, while 16 μl can be used to maximally cut or tear the mesh. More specifically, about 1 μl to 2 μl can be used to expand the Schlem tubes and collecting tubes; about 2 μl to 4 μl can be used to expand the Schlem tubes and collecting tubes and extend the proximal tubular tissue; and about 4 μl to 6 μl can be used for all of the foregoing and to create microfractures or microperforations in the trabecular mesh and proximal tubular tissue (further increasing porosity and outflow). Volumes of about 8 μl to 16 μl can be used for all of the foregoing and for basic perforation/tearing of the trabecular mesh and proximal tubular tissue. Volumes of about 16 μl to 50 μl can be used for substantially or completely tearing or cutting the trabecular mesh.

The total volume of viscoelastic fluid can be delivered along a 360-degree arc (1600) of the Schlemm tube during a single advance or removal (1604) of the elongated component from a single entry point (1602) in the tube (e.g., as shown in Figure 16), or along smaller arcs during multiple advances or removals of the elongated components. For example, as shown in Figure 17, the elongated component (1700) can advance along a 180-degree arc of the tube in both clockwise (1702) and counterclockwise (1704) directions to deliver fluid from, for example, a single entry point (1706) in the tube. Referring to Figures 16 and 17, an exemplary destructive volume between approximately 4 μl and approximately 18 μl can be delivered along the 360-degree arc of the tube as the elongated component advances from a single entry point in the tube, or an exemplary destructive volume between approximately 2 μl and approximately 9 μl can be delivered along the 180-degree arc of the tube during two advances of the elongated component from a single entry point in the tube (one clockwise and the other counterclockwise). More specifically, an exemplary destructive volume of approximately 9 μl can be delivered along the 360-degree arc of the tube, or an exemplary destructive volume of approximately 4.5 μl can be delivered along the 180-degree arc of the tube during each of the two advances. The elongated component can enter the tube from a single point or from multiple points.

Additionally, the fluid composition can be delivered to restore the tubular anatomy of the Schlem's tube, clear blockages within the tube, rupture the trabecular meshwork of the proximal tubules or the inner wall of the Schlem's tube, or expand the tube. Here, the delivery system may include threads, tubes, balloons, instruments for delivering energy to tissue, and/or other features that contribute to these methods. It is anticipated that such systems with additional features can be used to treat glaucoma. The surfaces of these systems may also be roughened or have protrusions to further rupture the inner wall of the Schlem's tube and the trabecular meshwork of the proximal tubules, thereby increasing aqueous humor outflow or permeability.

Viscoelastic fluid can be delivered while simultaneously advancing an elongated component of a single-handed, single-operator controlled device in a clockwise, counterclockwise, or both direction, or during withdrawal of the elongated component from the Schlem tube. As previously stated, viscoelastic fluid can be delivered to rupture the Schlem tube and surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid can induce rupture by: dilating the Schlem tube; increasing the porosity of the trabecular meshwork; stretching the trabecular meshwork; creating microfractures or perforations in the proximal tubule tissue; removing collagen septa from the Schlem tube; dilating the collection tube, or combinations thereof. At the onset of ocular surgery, the elongated component can be loaded with viscoelastic fluid, allowing the fluid to be delivered via a single device. This contrasts with other systems that use forceps or other advancing tools to insert a fluid delivery catheter into the Schlem tube and/or devices containing viscoelastic fluid, either alone or independently of the delivery catheter or catheter advancing tool, which require connection to the delivery catheter or catheter advancing tool by an assistant during surgery, while the delivery catheter or catheter advancing tool is held by the surgeon.

Tool delivery

Before the introduction of goniotomy and trabeculotomy (both commonly used to treat obstructed trabecular meshwork, often hereditary in young age), congenital glaucoma invariably resulted in blindness. Regardless of the invasiveness of goniotomy (performed via an internal approach, but using a sharp scalpel to cut the mesh at 30 to 60 degrees to improve outflow) and trabeculotomy (an external approach where a deep scleral incision removes Schlemm's canal and the mesh is cut with a probe), the procedures were considered effective and have potentially prevented lifelong blindness in many pediatric patients. In 1960, Burian and Smith independently described external trabeculotomy. In this highly invasive external procedure, the surgeon makes a deep scleral incision, locates the Schlem canal, and externally inserts a catheter or a specially designed probe called a trabeculotomy knife into the full 360 degrees of the Schlem canal. Finally, the ends of the catheter or probe are pulled taut to the point where the trabeculotomy knife cuts through the entire trabecular meshwork into the anterior chamber to improve drainage.

Recent attempts by NeoMedix to reduce the invasiveness of external trabeculotomy have led to the commercialization of a device called the "Trabectome." The Trabectome aims to make trabeculotomy easier by using an internal approach. The instrument and method involve internal removal of the trabecular meshwork using an electrocautery device that also provides infusion and aspiration. The Trabectome has three main disadvantages: 1) the device uses an energy-based mechanism to ablate the trabecular meshwork, which is believed to cause inflammation and scarring in the eye, potentially adversely affecting outflow and pressure; 2) the device/surgery is ergonomically limited—in addition to being limited to meshwork treatment with an entry angle of 60 to 120 degrees per corneal or scleral incision, it requires a foot pedal and power cord to activate the electrocautery and irrigation; and 3) due to its energy-based ablation and irrigation, it requires capital equipment.

The methods (and systems and devices) described herein, including those for applying destructive forces to trabecular tubule tissue, are highly suitable for endoscopic trabeculotomy and anterior chamber goniotomy due to their avoidance of the use of an electrocautery device, and enable the advancement of elongated components along a greater degree of curvature of the Schlemm canal. When the systems and devices are adapted to apply destructive forces to trabecular tubule tissue, implant-free methods can be employed, for example, by delivering a destructive volume of viscoelastic fluid to advance a destructive tool (e.g., a cannula, elongated component, catheter, etc.) or both. In some examples, the destructive tool may include a destructive component on its distal portion. Exemplary destructive components include (but are not limited to) notches, hooks, barbs, balloons, or combinations thereof. In other examples, the destructive tool may not include a destructive component on its distal portion and may actually have a non-traumatic, blunt distal portion. Exemplary non-traumatic distal portions include (but are not limited to) umbrella-shaped or dome-shaped distal portions.

In some variations of the internal trabeculotomy and anterior chamber goniotomy methods, the procedure includes: advancing a cannula at least partially through the anterior chamber of the eye; entering the Schlem canal at a single entry point using the cannula; and delivering a volume of viscoelastic fluid through an elongated component comprising a lumen and slidable within and expandable to the cannula, sufficient to rupture the structure of the Schlem canal and surrounding trabecular tubules to reduce intraocular pressure. Other methods for treating ocular conditions include: entering the Schlem canal using an elongated component expandable from a single operator-controlled handle comprising a reservoir; and delivering a volume of viscoelastic fluid from the reservoir through the elongated component by increasing the pressure within the reservoir, wherein the volume of viscoelastic fluid delivered is sufficient to rupture the structure of the Schlem canal and surrounding tissues to reduce intraocular pressure. The destructive volume can be between about 2 μl and about 16 μl. In one variation, the destructive volume is about 4 μl of viscoelastic fluid. As previously stated, in some cases, the destructive volume can be any value between about 20 μl and about 50 μl. The fluid-based delivery method is described in more detail above.

When no fluid is used and only destructive tools are employed, the outer diameter of an elongated component or tool can be set to varying sizes to rupture tissue, similar to how the volume of a fluid can be varied to alter the degree of rupture. For example, an elongated component or tool with an outer diameter in the range of approximately 50 to approximately 100 micrometers can advance through the tube to slightly dilate it and rupture or remove collagen septa that obstruct circumferential tubular flow. An elongated component or tool with an outer diameter in the range of approximately 100 to 200 micrometers can be used to perform the foregoing and can also initiate the stretching of trabecular meshwork and proximal tubular tissue. An elongated component or tool with an outer diameter in the range of approximately 200 to approximately 300 micrometers can perform the foregoing but can also create microfractures in the trabecular meshwork and proximal tubular tissue and can maximize the dilation of collecting tubes. An elongated component or tool with an outer diameter in the range of approximately 300 to approximately 500 micrometers can maximize tissue rupture and can create tears or perforations along the entire trabecular meshwork and proximal tubular tissue. Furthermore, the further the elongated component or tool advances through the cannula, the better the surgical outcome. For example, for maximum efficacy and maximum intraocular pressure reduction, the elongated component or tool can advance outward from the tip of the cannula to approximately 30 degrees of curvature (e.g., advancing approximately 3mm to 4mm away from the cannula), approximately 60 degrees of curvature (e.g., advancing approximately 6mm to 8mm away from the cannula), approximately 90 degrees of curvature (e.g., advancing approximately 10mm away from the cannula), approximately 120 degrees of curvature (e.g., advancing approximately 15mm away from the cannula), approximately 180 degrees of curvature (e.g., advancing approximately 20mm away from the cannula), or approximately a full 360 degrees of curvature (e.g., advancing approximately 36mm to 40mm away from the cannula). In some variations, the elongated component can have a non-uniform outer diameter. For example, the elongated component can have a tapered outer diameter, such that the outer diameter gradually increases from the distal to the proximal end.

In some variations, the method disclosed herein may involve advancing an elongated component (or tool) between approximately 5 degrees and approximately 360 degrees of arc in the Schlem tube. In some variations, the method may involve advancing the elongated component (or tool) to approximately 360 degrees of arc, approximately 270 degrees of arc, approximately 120 degrees of arc, approximately 180 degrees of arc, or approximately 90 degrees of arc in the Schlem tube. In still other variations, the advancement of the elongated component (or tool) may be approximately 0 to 5 degrees of arc, approximately 30 degrees of arc, or approximately 60 degrees of arc in the Schlem tube. Advancement may occur from a single point of entry in the Schlem tube or from multiple points of entry in the tube. When a destructive force is to be applied, it may be beneficial to advance the elongated part about 180 degrees of arc from a single entry point in the Schlemm tube in both clockwise and counterclockwise directions.

Depending on factors such as the type or severity of the condition being treated, destructive forces can be applied to partially or completely destroy and/or remove the trabecular meshwork, and this can be adjusted by changing the tool configuration. In some methods, the trabecular meshwork may rupture during the advancement of the slidable elongated member. The body segment of the elongated member, near the tip, can be customized with one or more notches, and barbs or balloons that snap the mesh can be used as the distal tip is guided and advanced along the Schlem tube, thereby rupturing, partially tearing, completely tearing, and/or removing the trabecular meshwork after advancement. Alternatively, implants with edges specifically designed to cut the mesh can be used.

In other cases, the trabecular mesh may rupture during the contraction of the slidable elongated component. Other methods for rupturing the tissue may involve custom-designed systems (e.g., elongated components, any catheter or suture, probe tip, etc.) that contract to snap or grab the mesh after it has fully advanced through the tube. This may be done using sutures with curved tips, hooks, notches, or barbs at their ends, which advance through the lumen of the catheter, then hook the mesh after contraction, tearing or completely removing the mesh along its length, or simply using metal or polymer sutures or sutures (without catheters) with hooked, serrated, or barbed tips that allow them to enter the Schlemm tube without tearing the mesh but hooking, tearing, and/or completely removing it after contraction. Alternatively, as shown in Figure 18C, the elongated component (1806) may incorporate a destructive tool, such as a sharp-edged element (1808), which may cut or tear the beam mesh when retracted into a sleeve (1800) that remains stationary. An exemplary sharp-edged element could be a hook, thread, or any other suitable shape memory component that may extend from the sleeve to tear, cut, or remove the beam mesh.

Another method for rupturing tissue may involve using an excessively large elongated component (e.g., having an outer diameter of 300 to 500 micrometers) to tear the mesh after delivery, or expanding or inflating the elongated component after it has been fully inserted into the Schlem tube to cause the mesh to stretch, rupture, break, or completely tear. For example, a catheter/elongated component, probe, or thread (with or without an inner lumen) with a tip outer diameter of 200 to 250 micrometers but having an axis that begins to expand outward after 3 clock hours in the Schlem tube (i.e., marked at about 5 or 10 mm on the catheter/elongated component) up to about 300 micrometers, about 400 micrometers, or about 500 micrometers, may be used such that as the tip advances easily within the Schlem tube, the enlarged axis follows and causes the trabecular mesh to break upon its contraction.

In another method, the cutting, breaking, removal, etc., of the trabecular mesh can be achieved by removing the sleeve from the eye while the elongated component remains in the tube, thereby tearing the mesh. Referring to Figure 18A, the sleeve (1800) can be inserted into the anterior chamber (1802) and the Schlemm tube (1804), and a tool (e.g., a sliding elongated component (1806)) can advance within the tube (1804). As shown in Figure 18B, the sleeve (1800) can be removed from the anterior chamber (1802) without retracting the elongated component (1806). This action itself can tear the trabecular mesh. When the sleeve (1800) is removed from the anterior chamber (1802), the elongated component (1806) can begin tearing the trabecular mesh from the point where the sleeve (1800) is inserted into the Schlemm tube (1804), and can continue tearing around the trabecular mesh toward the distal end of the elongated component.

Variations of the method described herein are illustrated in Figures 29A through 29D and can be performed using, for example, a delivery system described with respect to Figures 23A through 23F. Figure 29A shows a flowchart illustrating the method. The method can be used to access the trabecular drain system using a single clear corneal incision and can allow transluminal trabeculotomy up to 360 degrees. The method can use a flexible elongated member that can be advanced and retracted using a single-handed, disposable manual instrument. First, the device can be removed from its encapsulation. Subsequently, the lock can be removed from the delivery system. The cannula can be accessed into the anterior chamber through an existing corneal or scleral incision. An incision of at least about 1 mm width may be required. The distal tip of the cannula can be used to pierce the trabecular meshwork to access the Schlem canal. When the flexible elongated member is inserted into the Schlem canal, the cannula can be firmly held against the corner. One or more of the exposed portions of the rollers can be rotated proximally to advance the flexible elongated member around the Schlem canal up to about 180 degrees (about 20 mm of circumferential tube travel). At this point, the elastic, slender component can be fully extended, and the rollers can no longer rotate. During this procedure, direct microscopy or gonioscopy of the cannula tip can be maintained, and the anterior chamber can be maintained by viscoelastic or continuous balanced saline infusion.

Once the elastic elongated member advances, the sleeve can be removed from the eye through the cut without retracting the elastic elongated member. This allows the elastic elongated member to cut the trabecular mesh. In some cases, it may be necessary to bias the distal tip of the sleeve toward the trabecular mesh being cut; this may help prevent the elastic elongated member from slipping out of the tube during sleeve removal. Removal of the sleeve (2900) without retracting the elastic elongated member (2902) to tear the trabecular mesh (2904) is illustrated in Figures 29B-29D. As can be seen here, the elongated member (2902) transmits the force of removing the sleeve (2900) as a force for tearing the trabecular mesh. The removal of the sleeve (2900) causes a “pull-out” effect that tears the trabecular mesh. That is, the trabecular mesh is torn from its proximal end to its distal end through the body of the elongated member (2902). First, the force on the trabecular mesh from the proximal end of the body of the elongated component (2902) causes the trabecular mesh to tear near the insertion point of the sleeve (2900). As the sleeve (2900) continues to be removed from the eye, as shown in Figures 29C and 29D, the body of the elongated component (2902) continues to tear the trabecular mesh toward the distal tip of the elongated component. It should be noted that this method causes the trabecular mesh to tear gradually from the first location (the proximal end of the extended elongated component, near the insertion point of the sleeve) to the second location (the distal end of the extended elongated component), as opposed to simultaneous cutting or tearing along the distance from the first location to the second location. Furthermore, it should be noted that in this method, each portion of the trabecular mesh is not torn by a single feature of the elongated component (e.g., the distal end of the elongated component after advancement or contraction); in fact, each portion of the trabecular mesh is torn by the portion of the elongated component adjacent to it after the elongated component has advanced.

After the delivery system is completely removed from the eye, the flexible elongated component can be retracted back into the cannula via one or more of the distally rotating rollers. Once the flexible elongated component is fully retracted, the delivery system can be flipped so that the cannula tip rotates 180 degrees to face the opposite direction. The cannula tip can then be inserted into the anterior chamber through a corneal or scleral incision, and the distal tip can be inserted into the same inlet that leads into the Schlemm cannula. The method described above can then be repeated on the second half of the Schlemm cannula to cut the trabecular meshwork. In some cases, a viscoelastic agent can be used to impede any blood return to the anterior chamber.

At the end of the procedure, the anterior chamber can be flushed through the corneal wound (e.g., with a balanced salt solution) (manually or automatically). If necessary, a balanced salt solution or viscoelastic agent can be used to reform the anterior chamber to achieve physiological pressure and further impede any blood return from the collection tube into the anterior chamber. If necessary, sutures can be used to seal the corneal or scleral incision. Postoperatively, antibiotics or antiseptics, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for weeks or months to help prevent adhesions and corneal closure.

In other methods, tissue rupture can be achieved by internally delivering a suture throughout the Schlemm canal, which is then sufficiently stretched to extend the canal, causing the trabecular meshwork to rupture and/or tear through the meshwork (“internal suture trabeculotomy”). Here, a tool including a grasping element can be used to pull the distal suture tip inward as the cannula is being removed from the eye, severing the entire 360-degree or a segment of the trabecular meshwork, or to tie the suture ends together to provide tension to the meshwork without tearing it.

External approach

External approaches for implanting ocular devices or delivering fluid compositions can include additional or slightly different steps. For example, the creation and suturing of a tissue flap can be part of an external approach. Generally, an external approach for implanting an ocular device may include the following steps: First, under microscopic imaging, the conjunctiva is incised, a scleral flap is created, and tissue is dissected to identify the opening into the Schlemm's canal. The anterior chamber can be infused with saline alone, or it may contain a viscoelastic composition placed in the anterior chamber to prevent anterior chamber angle collapse. The procedure can be performed as a standalone surgery or in combination with cataract surgery in a pre-defined mode. It can also be performed before or after the cataract surgery portion.

Using the delivery system described herein, a cannula can be inserted into the Schlemm canal, and the ocular device is advanced under direct microscopic imaging or via a gonioscope or gonioscope using a positioning element. When the ocular device has advanced the required amount, the surgeon can release the ocular device from the positioning element via an actuating engagement mechanism and remove the delivery system from the eye and surgical area. The scleral wound can be self-sealing, or it can subsequently be closed using, for example, sutures or tissue adhesives. If repositioning of the ocular device is required or desired, the surgeon can use the positioning element of the delivery system to retract and/or advance the ocular device.

Regarding the delivery of the fluid composition, the external approach is similar to the internal approach. However, the delivery system uses a sliding, elongated component to infuse the fluid composition into the Schlemm canal, instead of using a positioning element. First, under microscopic imaging, the conjunctiva is incised, a scleral flap is created, and tissue is dissected to identify the opening into the Schlemm canal. The anterior chamber can be infused alone with saline or may contain a viscoelastic composition placed within the anterior chamber to prevent anterior chamber angle collapse. The procedure can be performed as a standalone surgery or in combination with cataract surgery in a pre-defined mode. It can also be performed before or after a portion of cataract surgery.

Using the delivery system described herein, under gonioscopy, a cannula can be inserted into a Schlem tube, and an elongated component coaxially positioned within the cannula's lumen can be inserted into the tube. Once the elongated component is positioned within the tube, a fluid composition (e.g., a viscoelastic fluid) can be delivered continuously or intermittently through the elongated component. The fluid composition may exit the lumen of the elongated component through its distal end (e.g., through its distal tip), or through an opening or perforation provided along its axis, or a combination of both. The opening or perforation may be spaced along the axial length of the elongated component in any suitable manner, for example, symmetrically or asymmetrically spaced along its length. Other substances, such as drugs, air, or gases, may be delivered in the same manner if necessary. The elongated component can be repositioned by contraction or repeated advance and contraction. The delivery system can then be removed from the eye.

The configuration of an ocular delivery system can be advantageous in many different aspects. In one aspect, the delivery system can be used for endoscopic methods of implanting ocular devices in the Schlem canal or for delivering fluid compositions or tools into the canal. In another aspect, the delivery system cannula is configured to allow easy and non-invasive access to the Schlem canal. Furthermore, the delivery system is configured entirely within a single instrument in a manner that gives surgeons greater freedom of use. For example, the system's handle is configured to be used with either side facing upwards (i.e., by flipping the handle or rotating the cannula). Thus, the delivery system is designed to be used with either hand and in either eye in a clockwise or counterclockwise direction. For example, the delivery system can be used counterclockwise with either the right or left hand to access the Schlem canal, or counterclockwise with both the right and left hands in either eye to access the canal. Thus, access to the canal from all four quadrants of the eye is possible. In another aspect, the delivery system includes a one-handed, single-operator controlled device configured to provide a force sufficient to rupture the Schlemm tube and surrounding tissue to improve flow through the trabecular tube outflow path. The system typically combines an inlet cannula, a delivery elongated component, an elongated component advance mechanism, a destructive tool, and a viscoelastic fluid into a single device, making it possible for a single person or one hand to advance the elongated component or tool or deliver fluid.

Methods for manufacturing casing

As mentioned above, the cannula described herein can be configured to both pierce trabecular meshwork or other tissues and reversibly deliver elongated components without cutting, breaking, or otherwise damaging them. To achieve this dual purpose, the cannula can be manufactured with a distal end comprising both a sharp portion and a blunt or blunt portion. Generally, the method of manufacturing the cannula described herein may include: creating a bevel at the distal tip; sharpening the distal tip to form a sharp piercing tip; smoothing a portion of the distal tip of the cannula; and bending a portion of the cannula along its longitudinal axis. In some variations, the method may also include: obtaining a cannula of appropriate working length; roughening the outer surface of the cannula; applying a protective cap to a portion of the distal tip; polishing a portion of the cannula; and cleaning the cannula.

Figure 19 depicts an exemplary method of manufacturing a sleeve for use with the apparatus, systems, and methods described herein. As shown herein, a method of manufacturing a sleeve (1900) may include: obtaining a sleeve of appropriate working length (1902); roughening the outer surface of the sleeve (1904); creating a bevel at the distal tip of the sleeve (1906); sharpening the distal tip of the sleeve (1908); applying a protective cap to a portion of the distal tip of the sleeve (1910); smoothing a portion of the distal tip of the sleeve (1912); bending the sleeve (1914); polishing the sleeve (1916); and cleaning the sleeve (1918). It should be understood that although the method steps in Figure 19 are depicted in a specific order, many of the steps may be performed in a different order, and some of the steps may optionally be performed together, as discussed in more detail below.

To begin the process, a sleeve of appropriate working length (1902) can be obtained. During the sleeve manufacturing process, sleeves pre-cut to the required working length can be purchased, or raw materials for forming the sleeve (e.g., stainless steel hypodermic tubes) can be purchased in bulk and cut to appropriate lengths. Damage or other visual defects in the sleeve can be inspected after acquisition and throughout the manufacturing process. In some variations, the working length (i.e., the length suitable for disposal of the sleeve during manufacturing) can correspond to the final required length of the sleeve. In other variations, for ease of manufacturing, for example, the working length can be longer than the required length, and the sleeve can be cut or shortened to the final required length at any time during the manufacturing process (e.g., by cutting the proximal end of the sleeve), included as the final step of the process. Exemplary working lengths include (but are not limited to) between about 50 mm and about 70 mm, between about 40 mm and about 90 mm, and more precisely, about 60 mm.

The proximal end of the casing can be cut, processed, and/or trimmed at any time during the manufacturing process. In some cases, the proximal end of the casing can be vertically cut (i.e., cut substantially perpendicular to the longitudinal axis of the casing). The edges of the proximal end can be smoothed or rounded using any suitable method (e.g., by media blasting). This smoothing of the proximal end of the casing prevents cutting, tearing, or otherwise damaging the slender component. For example, smoothing the proximal end can remove any sharp edges or serrated surfaces and can remove any debris or deposits remaining in the lumen from the cutting process. The proximal end of the casing can be inspected after smoothing, and if sharp or serrated edges still exist, the proximal end can be further smoothed.

In some variations, the outer surface of the sleeve can optionally be roughened (1904) or textured, which can help attach the sleeve to the handle. For example, in some cases, the proximal or central portion of the outer surface of the sleeve can be sandblasted to create a textured or roughened surface to which adhesives can be applied. Sandblasting the outer surface of the sleeve can increase the surface area of the sandblasted portion, which can provide better adhesion between the handle and the sleeve.

As described above, the distal end of the cannula can be beveled. A bevel (1906) can be created by cutting or grinding the distal end of the cannula at an angle relative to its longitudinal axis. More specifically, the bevel can be mounted such that it traverses and cuts across the lumen of the cannula. Figure 3 depicts a side view of a cannula (300) including a bevel (312) at its distal tip (306). The bevel (312) can include an angle (A) between about 5 degrees and about 85 degrees. As mentioned above, the angle (A) may be important for properly piercing the trabecular meshwork and entering the Schlemm tube without damaging other surrounding tissues, and/or for adequately observing the advance and retraction of the elongated component. In some variations, the angle (A) can be approximately 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 85 degrees. In some variations, the angle (A) can be between approximately 23 and approximately 27 degrees. In some of these variations, the angle (A) can be approximately 25 degrees.

Figure 20 depicts a perspective view of the distal tip (2002) of the sleeve (2000) after the bevel has been formed. As shown, the beveled distal tip (2002) now includes a proximal end (2008) and a distal end (2010). Furthermore, forming a bevel at the distal tip (2002) elongates the opening (2012) at the distal tip (2002), resulting in an elliptical (instead of a circular) opening. Therefore, the beveled distal tip (2002) yields an angled elliptical inner cavity opening such that the top of the elliptical opening is closer to the proximal portion of the sleeve than the bottom of the elliptical opening. The inner and outer circumferential edges (2004, 2006) are also shown in Figure 20.

Although the bevel can create a sharp edge, and in some cases a sharp distal tip, it may be necessary to further sharpen a portion of the distal tip of the sleeve to obtain easier access to the Schlemm tube with greater precision. Therefore, in some cases, after the bevel has been created, the distal tip may be further sharpened (1908) to create a sharp piercing tip that can further aid in piercing the trabecular mesh. The distal tip can be sharpened using any suitable method, for example, by grinding or otherwise removing a portion of the outer surface and/or a portion of the outer circumferential edge of the distal end of the sleeve. To minimize unwanted sharp edges that could damage elongated components, it may be necessary to maintain as much wall thickness as possible at the distal tip and ensure that the wall thickness is uniform. It may also be beneficial to prevent the formation, accumulation, adhesion, or other deposition of sleeve material or other sharpening byproducts on the inner surface of the sleeve within the lumen. Such material may fragment, creating protrusions or sharp surfaces or edges that could cut or damage elongated components when the delivery system is in use.

Figures 21A and 21B depict a perspective view and a front view, respectively, of a variation of the distal tip (2100) of a sleeve, comprising a bevel (2102) and a sharp puncture tip (2114). The distal tip (2100) also includes a proximal end (2108), a distal end (2110), inner and outer circumferential edges (2104, 2106), and an internal opening (2112). The sharp puncture tip (2114) can be produced by grinding the distal end (2110) of the distal tip (2100), thereby creating two angled surfaces (2116) converging to form a apex. The angled surfaces (2116) can produce any suitable angle formation of the sharp puncture tip (2114). For example, in some instances, the angled surface (2116) may have an angle (B) of approximately 20, 25, 30, 35, 40, 45, or 50 degrees relative to the longitudinal axis of the distal tip (2100), between approximately 25 and approximately 50 degrees, or between approximately 37.5 and approximately 42.5 degrees. Thus, in some variations, the angle between the two angled surfaces (2116) may be between approximately 50 and approximately 100 degrees. It should be understood that although the distal tip (2100) is depicted with two angled surfaces, a distal tip with a single angled surface may also be used.

Returning to Figure 19, the method for manufacturing the sleeve (1900) may further include polishing a portion of the distal tip of the sleeve (1912). In a variation where the distal tip of the sleeve is sharpened, as described above with respect to Figures 21A and 21B, the method may further include applying a protective cap to the sharp portion of the distal tip (1910), for example, the distal end of a sharp piercing tip (2114) and/or an angled surface (2116), before polishing the distal tip (1912). In a variation where the distal tip is not sharp after being angled, applying a protective cap to the distal end of the distal tip may still be desirable (as described above with respect to Figure 20). Applying a protective cap may help maintain a sharp edge during polishing.

As mentioned above, the distal tip of the cannula can be configured to both pierce tissue and deliver elongated components. These elongated components are themselves susceptible to puncture, cutting, severing, or other damage by the cannula. To protect these elongated components, it may be important to smooth or deburr the surfaces and/or edges of the distal tip of the cannula that the elongated component may come into contact with. For example, referring again to Figures 21A and 21B, in some variations, a portion of the inner and/or outer circumferential edges (2104, 2106), the surfaces between said edges (2118), and/or the inner and/or outer surfaces of the cannula adjacent to the opening (2112) may be smoothed. This may even make these edges and surfaces flat and/or non-sharp. For example, it may be necessary to smooth a portion of the inner circumferential edge (2104) at the proximal or distal end (2108, 2110) of the distal tip (2100), or to smooth the entire inner circumferential edge. In some examples, a portion of the outer circumferential edge (2106) may also be smoothed while maintaining the sharp edge of the distal tip (e.g., a sharp piercing tip). For example, a portion of the outer circumferential edge (2106) may be smoothed at the proximal end (2108) of the distal tip (2100), or the entire outer circumferential edge (2106) up to the angled surface (2116) may be smoothed. Additionally, it may be necessary to smooth or deburr the surfaces between the edges (2118) and/or the opening (2112) adjacent to the proximal end (2108) or distal end (2110) of the distal tip (2100), or the inner or outer surface of the sleeve circumferentially surrounding the opening (2112).

The distal tip (2100) of the sleeve can be deburred, smoothed, flattened, rounded, blunted, etc., using any suitable mechanism. For example, smoothing the distal tip of the sleeve can include mechanical and/or manual deburring, abrasive or soda blasting, sanding, grinding, cleaning with a wire brush, laser cutting, polishing (e.g., electropolishing), combinations thereof, etc.

Returning to Figure 19, the method of manufacturing the cannula (1900) may further include bending the distal portion of the cannula (1914) to form the distally bent portion described above. The bent cannula can properly orient the distal tip so that it can pierce the trabecular meshwork without damage. Referring back to Figure 3, in some variations, the distal portion of the cannula may be bent such that the sharp puncture tip is positioned along the outer radius (322) of the bent cannula. In some examples, the distal portion of the cannula may be bent relative to the outer surface of the proximal portion of the cannula at an angle between approximately 100 degrees and approximately 125 degrees, approximately 115 degrees and approximately 125 degrees, or approximately 118 degrees.

The distal portion of the sleeve can be bent using any suitable mechanical or manual bending process. It may be important to choose a bending process that does not alter the cross-sectional size and shape of the sleeve during the bending process. Additionally, it should be understood that the sleeve can be bent at any point during the manufacturing process, and bending does not necessarily occur after the distal tip of the sleeve has been smoothed, as depicted in the method (1900) in Figure 19.

The method of manufacturing the sleeve (1900) may optionally include polishing (1916) all or part of the sleeve, for example, polishing the distal tip of the sleeve. In variations of sleeve polishing, polishing the sleeve (1916) may remove debris, markings, dents, grooves, etc., remaining on the surface of the sleeve. These markings may be remnants from any part of the manufacturing process, and specifically, may arise from creating a bevel at the distal tip of the sleeve (1906), sharpening the distal tip of the sleeve (1908), and/or smoothing a portion of the distal tip of the sleeve (1912). Polishing the sleeve (1916) may be particularly suitable for variations of processes that typically leave debris or markings (e.g., laser removal) in smoothing a portion of the distal tip of the sleeve (1912). The polishing of the sleeve (1916) may be completed using any suitable method, for example, electropolishing, staged media blasting using a medium with increased particle size, etc.

If necessary, the sleeve may be cleaned before it is installed into the delivery system described herein (1918). For example, in some variations, the sleeve may be passivated to remove iron oxide or other contaminants. In some examples, an acid similar to, for example, nitrogen oxide may be used to passivate the sleeve. In other variations, a cleaning agent, an ultrasonic bath, or any other suitable cleaning process may be used to clean the sleeve.

The cannula and/or the assembled delivery system can be sterilized using, for example, gamma irradiation. Gamma irradiation doses may range, for example, from 25 kGy to 40 kGy. Other irradiation energies can be used for sterilization, such as electron beam irradiation. Alternative sterilization methods include gas sterilization, such as ethylene oxide gas sterilization. In variations where all or part of the system is reusable, as described herein, these parts can be sterilized and reused. For example, in a variation where the handle is reusable and the cannula and elongated parts are disposable, after use, the used cannula and elongated parts can be removed, the handle is sterilized, and a new cannula and elongated parts are attached to the sterile handle.

Although the inventive apparatus, system, kit, and method have been described in detail by way of description, this description is for purposes of clarity only. It will be readily apparent to those skilled in the art that, in light of the teachings herein, certain changes and modifications may be made without departing from the spirit and scope of the appended claims.

Claims (23)

1. A device for treating an eye condition, comprising: The device includes an elongated component with an inner cavity, a fluid assembly including a fluid reservoir fluidly connected to the inner cavity of the elongated component, and a linear gear connected to the fluid assembly via a connecting rod. The elongated component is configured to advance into the Schlem tube of the eye via a linear gear and a fluid reservoir, and the device is configured to maintain a fixed distance between the proximal end of the linear gear and the distal end of the fluid reservoir during advancement via the connecting rod. The elongated component is also configured to retract, and the device is configured to deliver a fluid composition from the fluid reservoir to the Schlemm tube by reducing the distance between the proximal end of the linear gear and the distal end of the fluid reservoir via the connecting rod as the elongated component retracts. 2. The apparatus according to claim 1, wherein the apparatus further comprises a housing. 3. The apparatus of claim 2, wherein the fluid assembly is configured to move distally rather than proximally relative to the housing. 4. The apparatus of claim 2, wherein the fluid assembly is configured to move relative to the distal end of the housing during the advance of the elongated member and to be fixed relative to the housing during the retraction of the elongated member. 5. The device of claim 4, wherein the housing includes teeth that allow the fluid assembly to move relative to the distal end of the housing during the advance of the elongated member and to hold the fluid assembly relative to the housing during the retraction of the elongated member. 6. The apparatus of claim 2 further includes a lock configured to prevent movement of the fluid assembly relative to the housing prior to use. 7. The apparatus of claim 2, wherein the apparatus further comprises a sleeve coupled to a distal end of the housing. 8. The apparatus of claim 7, wherein the elongated member includes a distal end, and wherein the distal end of the elongated member is slidable within the sleeve between a retracted position and an extended position, wherein the distal end is located within the sleeve in the retracted position and distal to the distal tip of the sleeve in the extended position. 9. The apparatus of claim 1, wherein the translation of the linear gear retracts the elongated member and delivers the fluid composition from the fluid reservoir through the inner cavity of the elongated member. 10. The apparatus of claim 9, wherein the volume of the fluid composition delivered corresponds to the translational distance of the linear gear. 11. The apparatus of claim 1, wherein the connecting rod and the linear gear are movably connected to each other. 12. The apparatus of claim 11, wherein the linear gear is configured to move relative to the connecting rod and toward the fluid reservoir during the retraction of the elongated member. 13. The apparatus of claim 11, wherein the proximal end of the link is fixedly attached to the fluid assembly, and the distal end of the link is attached to the linear gear via a one-way ratchet. 14. The apparatus of claim 1, further comprising a plunger, wherein the plunger includes a lumen and a proximal end, wherein the fluid reservoir is fluidly connected to the lumen of the elongated member via the lumen of the plunger, and wherein the proximal end of the plunger is slidably located within the fluid reservoir such that the proximal end of the plunger moves from an extended position to a depressed position within the fluid reservoir, causing the plunger to discharge a fluid composition from the fluid reservoir, and wherein the discharged fluid composition travels through the lumen of the plunger into the lumen of the elongated member. 15. The apparatus of claim 1, further comprising a drive assembly including a linear gear and a rotatable component, wherein rotation of the rotatable component causes translation of the linear gear. 16. The apparatus of claim 1, wherein the elongated member is configured to advance in a first direction into the Schlem tube of the eye via a linear gear and a fluid reservoir, the elongated member is further configured to advance in a second direction into the Schlem tube via a second advance of the linear gear and the fluid reservoir, and wherein the elongated member is further configured to retract a second time, and the apparatus is further configured to deliver a fluid composition through the elongated member into the Schlem tube during the second retraction of the elongated member by further reducing the distance between the proximal end of the linear gear and the distal end of the fluid reservoir. 17. The apparatus of claim 16, wherein the fluid reservoir is configured to move distally to a first position during the advancement of the elongated member in a first direction within the Schlemm tube, and wherein the fluid reservoir is configured to move distally from the first position to a second position during the advancement of the elongated member in a second direction within the Schlemm tube. 18. The device of claim 1, wherein the elongated member is further configured to tear the trabecular mesh of the eye. 19. The apparatus of claim 18, wherein the body of the elongated member is configured to tear the beam mesh. 20. The apparatus of claim 1, wherein the apparatus is further configured to prevent the elongated member from advancing further after it has retracted a fixed cumulative distance. 21. The apparatus of claim 1, wherein the apparatus is configured to deliver a fluid composition of about 1 microliter to about 200 microliters out of the cavity of the elongated member. 22. The apparatus of claim 1, wherein the fluid assembly includes a Luer connector or a check valve for transferring the fluid composition into the fluid assembly. 23. The apparatus of claim 1, wherein the proximal end of the elongated member is fixed relative to the linear gear.