Intraocular delivery system and method

Abstract

To provide a suitable intraocular delivery system and method.SOLUTION: Described here are a system and a method for accessing Schlemm's canal and for delivering an ocular device, tool, or fluid composition therein. The ocular device may maintain the patency of Schlemm's canal without substantially interfering with transmural fluid flow across the canal. The fluid composition may be a viscoelastic fluid that is delivered into the canal to facilitate drainage of aqueous humor by disrupting the canal and surrounding trabecular capillary tissues. Some systems described here may be configured to cut or tear the trabecular meshwork with the body of an elongate member located within Schlemm's canal. Other tools for disrupting these tissues and minimally invasive methods for treating medical conditions associated with elevated intraocular pressure, including glaucoma, are also described.SELECTED DRAWING: Figure 25B

Description

[Technical field]

[0001] Described herein are systems and methods for accessing Schlemm's canal in an eye and delivering an ophthalmic device, instrument, or fluid composition therein. The ophthalmic device can maintain the patency of Schlemm's canal without significantly interfering with transmural, transcanalicular, circumferential, or longitudinal aqueous humor fluid flow across the canal. The resulting instrument can be used to disrupt the trabecular meshwork. The fluid composition can be a viscoelastic fluid that is delivered into the canal or aqueous humor collector channel to dilate the canal, disrupt the proximal canalicular network and adjacent Schlemm's canal walls, and / or increase aqueous humor permeability through the trabecular canalicular or transmural outflow pathways, thereby facilitating drainage of aqueous humor. Minimally invasive methods for treating medical conditions associated with elevated intraocular pressure, including glaucoma, are also described. [Background technology]

[0002] Glaucoma is a potentially blinding disease that affects over 60 million people worldwide, or approximately 1-2% of the population. Typically, glaucoma is characterized by elevated intraocular pressure. Increased pressure in the eye can cause irreversible damage to the optic nerve, which can lead to vision loss and, if left untreated, can progress to blindness. Consistent reduction of intraocular pressure can slow or halt the progressive vision loss associated with glaucoma.

[0003] Increased intraocular pressure is generally caused by suboptimal outflow or drainage of fluid (aqueous humor) from the eye. Aqueous humor or fluid is a clear, colorless fluid that is continually replenished in the eye. After being produced by the ciliary body, aqueous humor eventually exits the eye primarily through the trabecular meshwork. The trabecular meshwork extends circumferentially around the eye at the anterior chamber angle or drainage angle, which is formed at the intersection between the peripheral iris or iris root, the anterior sclera or scleral promontory, and the peripheral cornea. The trabecular meshwork drains outwardly into Schlemm's canal, a narrow circumferential passageway that generally surrounds the outer border of the trabecular meshwork. Aqueous veins or collector channels that receive the drained fluid are located around and extend radially from Schlemm's canal. Net drainage or outflow of aqueous humor may be reduced as a result of reduced outflow capacity, reduced outflow through the trabecular meshwork and Schlemm's drainage canals, increased episcleral venous pressure, or possibly increased production of aqueous humor. Flow from the eye can be restricted by blockages or narrowings in the trabecular meshwork and / or Schlemm's canal and its collector channels.

[0004] Glaucoma, pre-stage glaucoma, and ocular hypertension can currently be treated by reducing intraocular pressure using one or more modalities, including medications, incision surgery, laser surgery, cryosurgery, and other forms of surgery. Generally, medications and drug therapy are the first line of therapy. If drug therapy is not effective enough, more invasive surgical treatments can be used. For example, a standard incision procedure for reducing intraocular pressure is trabeculectomy or filtration surgery. This procedure involves creating a new drainage for the aqueous humor. Instead of the natural drainage through the trabecular meshwork, a new drainage path is created by removing a portion of the sclera and trabecular meshwork at the drainage angle. This creates an opening or passage between the anterior chamber and the subconjunctival space that is drained by the conjunctival blood vessels and lymphatics. The new opening can be covered by the sclera and / or conjunctiva to create a new reservoir called a bleb into which the aqueous humor can drain. However, traditional trabeculectomy procedures have both short-term and long-term risks. These risks include occlusion of the surgically created opening through scarring or other mechanisms, hypotony or abnormally low intraocular pressure, expulsion hemorrhage, hyphema, intraocular infection or endophthalmitis, shallow anterior chamber angles, macular hypotony, choroidal effusion, suprachoroidal hemorrhage, and others.

[0005] One alternative is to implant a device in Schlemm's canal that maintains the patency of the canal or assists the flow of aqueous humor from the anterior chamber into the canal. Various stents, shunts, catheters, and procedures have been devised for this purpose, with the implant or catheter being delivered to Schlemm's canal using an ab-externo (from outside the eye) technique. This placement method is invasive and typically lengthy, requiring the creation of a tissue flap and a deep incision to access the canal. In addition, locating and accessing Schlemm's canal via this external incision approach is very difficult for many surgeons due to the small diameter of Schlemm's canal, e.g., approximately 50-250 microns in cross-sectional diameter, and can become even smaller when collapsed. One such procedure, abexterno canaloplasty, involves creating a deep scleral incision and flap, locating and unroofing Schlemm's canal, circumnavigating all 360 degrees of the canal from outside the eye with a catheter, and using either viscoelastic, circumferential tension sutures, or both to help maintain canal patency. This procedure is extremely challenging and can take anywhere from 45 minutes to 2 hours. Although the long-term safety and effectiveness of canaloplasty is highly promising, the procedure remains surgically challenging and invasive.

[0006] Another alternative is viscocanalostomy, which involves injecting a viscoelastic solution into Schlemm's canal to dilate the canal and associated collector channels. Dilation of the canal and collector channels in this manner generally facilitates drainage of aqueous humor from the anterior chamber through the trabecular meshwork and Schlemm's canal and out of the natural trabecular outflow pathway. Viscocanalostomy is similar to canaloplasty (both invasive and abexternal), except that viscocanalostomy does not involve sutures and does not restore the full 360 degrees of outflow facility. Some advantages of viscocanalostomy are that it may avoid a sudden drop in intraocular pressure, hyphema, hypotony, and flattening of the anterior chamber. The risk of cataract formation and infection may also be minimized due to the reduction in intraocular manipulations, as well as complete eye wall penetration, anterior chamber opening and shallowing, and absence of iridectomy. An additional advantage of the viscocanalostomy is that the procedure avoids the need for external filtration and its associated short-term and long-term risks in the majority of eyes by restoring the physiological outflow tract, making the success of the procedure partially independent of conjunctival or episcleral scarring, which is the primary cause of failure in traditional trabeculectomy procedures. Furthermore, the absence of an elevated filtering bleb avoids the associated ocular discomfort and potentially serious ocular infections, and the procedure can be performed in either quadrant of the outflow tract.

[0007] However, current viscocanalostomy and canaloplasty techniques remain highly invasive because access to Schlemm's canal must be created by making a deep incision in the sclera, creating a scleral flap, and unroofing the Schlemm's canal. In their current form, both of these procedures are "ab-external" procedures. "Ab-external" generally means "from the outside," which is inherently more invasive given the location of Schlemm's canal and the amount of tissue disruption required to access Schlemm's canal from the outside. On the other hand, "ab-interno" means "from the inside," which is a relatively less invasive approach due to the reduced amount of tissue disruption required to access Schlemm's canal from the inside. As a result, the ab-interno approach to Schlemm's canal provides the surgeon with easier access to the canal while at the same time reducing the risk to the patient's eye and reducing patient morbidity. All of this leads to improved patient recovery and rehabilitation. Viscocanalostomy and canaloplasty procedures also remain challenging for surgeons because Schlemm's canal is difficult to find and access from the outside using deep incision techniques due to its small diameter. Yet a further drawback is that, at most, viscocanalostomy dilates Schlemm's canal, which is typically a 360-degree ring-shaped outflow canal-like structure, by 60 degrees. The greater the canal dilation, the more total aqueous humor outflow can be restored.

[0008] Therefore, it would be beneficial to have a system that provides easy and atraumatically access to Schlemm's canal using an abinterno technique for the delivery of intraocular devices, instruments, and compositions. It would also be useful to have a system that rapidly delivers devices, instruments, and compositions to Schlemm's canal to reduce procedure time and infection risk without sacrificing the safety and accuracy of the delivery procedure. It would also be useful to have a system that delivers devices, instruments, and fluid compositions to Schlemm's canal using an abinterno technique so that both cataract surgery and glaucoma surgery can be accomplished during the same surgery using the very same corneal or scleral incision. Such incisions are relatively small, allowing for less invasive surgery and faster patient recovery. This technique is called "abinterno" because it allows access to Schlemm's canal from inside the eye through the trabecular meshwork. Methods of using the present system to deliver intraocular devices, instruments, and compositions in a minimally invasive, ab-intern manner that effectively disrupt the proximal canalicular network and the wall of the adjacent Schlemm's canal, also known as the medial wall of Schlemm's canal, maintain the patency of Schlemm's canal, increase outflow, decrease resistance to outflow, or effectively dilate the canal and / or its collector channels would also be desirable. Summary of the Invention [Means for solving the problem]

[0009] Described herein are systems and methods for easily and reliably accessing Schlemm's canal with minimal or reduced trauma, as well as systems and methods for delivering intraocular devices (e.g., implants) therein. Other systems and methods may not include implants and / or rely on the delivery and removal of therapeutic (disruption) instruments and / or delivery of fluid compositions to Schlemm's canal to improve flow through the trabecular outflow system, which consists of the trabecular meshwork, adjacent canalicular tissue, Schlemm's canal, and collector channels. When implanted, the intraocular device may maintain the patency of Schlemm's canal without significantly interfering with transmural fluid flow across the canal. Transmural flow or transmural aqueous humor flow is defined as the flow of aqueous humor that begins at the outer wall of Schlemm's canal, continues from the anterior chamber across the trabecular meshwork into the lumen of Schlemm's canal, flows across and along the lumen of Schlemm's canal, and finally enters the aqueous humor collector channel. When a fluid composition is delivered to the canal, the fluid composition, e.g., a viscoelastic fluid, delivered to the canal may promote drainage of aqueous humor by expanding the canal, making the trabecular meshwork and the inner wall of Schlemm's canal more permeable to aqueous humor, and also expanding the aqueous humor collector channels. When a therapeutic instrument is delivered, the instrument may promote drainage of aqueous humor by expanding the canal, expanding the collector channels, disrupting or stretching the trabecular meshwork, disrupting or stretching nearby tubular tissue, tearing or cutting the trabecular meshwork or nearby tubular tissue, or completely removing the trabecular meshwork or nearby tubular tissue. Any or all of these actions may reduce resistance to outflow, increase aqueous humor outflow and drainage, and reduce intraocular pressure.

[0010] One of the beneficial features of the system may be a cannula configured with a distal curved portion that defines a radius of curvature where the radius of curvature directly engages a bevel at the distal tip of the cannula. However, in some variations, the system may include a straight cannula. A particular configuration of the handle of the system may also be useful. The handle may be sized and shaped to be easily operated with one hand. Additionally, the handle may be designed for general purpose operation. By "general purpose" it is meant that the handle is ergonomically configured for both right and left handed use, for use to access any quadrant of the eye, and for use in advancing a cannula or elongated member into Schlemm's canal in a clockwise or counterclockwise manner. Such a configuration may include a drive assembly that can be easily actuated in a first orientation (e.g., to deliver implants, instruments, and / or fluids in a clockwise manner) and in a second reversed orientation (e.g., to deliver implants, instruments, and / or fluids in a counterclockwise manner). Such a configuration may allow the drive assembly to be actuated using either the left or right hand, and may allow the drive assembly to be used for either the left or right eye, or in some variations the cannula itself may be rotated as much as necessary (e.g., 180 degrees) to provide ambidextrous usability in either clockwise or counterclockwise advancement directions.

[0011] The intraocular delivery systems described herein generally include a combination handle having a gripping portion and a housing having an inner end and a distal end. A cannula typically couples to and extends from the distal end of the housing. The cannula may include a proximal end and a distal curved portion, the distal curved portion having 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 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 generally include a drive assembly substantially contained within the housing, comprising a gear for converting rotational motion to linear motion.

[0012] If an intraocular device is to be implanted in Schlemm's canal, the system may further include a slidable positioning element having proximal and distal ends disposed coaxially within the lumen of the cannula. The distal end of the slidable positioning element may include an engagement mechanism for determining the position of the intraocular device within the canal (including manipulation of the device). Exemplary engagement mechanisms that may be used include hooks, jaws, clasps, forceps, or complementary interlocking elements for releasable attachment of the intraocular device.

[0013] The system may be configured to include a fluid assembly in the handle and an elongate member with a lumen that is coaxially disposed within the lumen of the cannula when the fluid composition is delivered to Schlemm's canal. The fluid composition may be delivered through a distal end of the lumen of the elongate member or through openings spaced along the axial length of the elongate member. In addition, the fluid assembly may be coupled to a loading component configured to transfer the fluid composition to a reservoir defined at least in part by the assembly. Some variations of the system may have the fluid composition preloaded in 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. It may be beneficial to use sodium hyaluronate as the viscoelastic fluid. Some systems may be configured to deliver a therapeutic (disruption) instrument to Schlemm's canal without delivering an implant or fluid. In these variations, the handle may or may not include a fluid reservoir, and the instrument may have various configurations for dividing tissue. An exemplary system may include an elongate member with an atraumatic distal tip configured to advance through Schlemm's canal, and a body of the elongate member configured to lacerate or cut the trabecular meshwork upon removal of the system from the eye.

[0014] A method for implanting an intraocular device into Schlemm's canal is also described. Using the intraocular delivery system disclosed herein, the method generally includes the steps of creating an incision in the eye wall that provides access to the anterior chamber of the eye, advancing a cannula of the system through the incision across a portion of the anterior chamber and into the trabecular meshwork to puncture the trabecular meshwork, accessing Schlemm's canal with the cannula, and implanting the device into the canal. The cannula will typically comprise a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal 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 a lumen extending from the proximal end through the distal tip. A positioning element that is slidable within the lumen of the cannula may be used during the step of implanting the device into the canal. The devices may be implanted to reduce intraocular pressure or to treat medical conditions such as glaucoma, pre-stage glaucoma, or ocular hypertension.

[0015] A method for delivering a fluid composition to Schlemm's canal is further described. Using the intraocular delivery system disclosed herein, the method generally includes the steps of creating an incision in the eye wall that provides access to the anterior chamber of the eye, advancing a cannula of the system through the incision into the trabecular meshwork, accessing Schlemm's canal with the cannula, and delivering a fluid composition to Schlemm's canal using an elongated member that has a lumen and is slidable within the lumen of the cannula. The cannula will typically have a proximal end and a distal curved portion, 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 a lumen extending from the proximal end through the distal tip. The fluid composition may be delivered to Schlemm's canal through the distal end of the elongated member or through openings spaced along the axial length of the elongated member. Fluids such as saline and viscoelastic solutions can be delivered to the canal to expand the canal and collector channel and / or disrupt the inner wall of the proximal canalicular network or Schlemm's canal to enhance aqueous humor permeability and reduce resistance to aqueous humor outflow or increase aqueous humor outflow. Examples of viscoelastic solutions are solutions containing hyaluronic acid, chondroitin sulfate, cellulose, and derivatives and mixtures thereof. As mentioned above, it may be beneficial to use sodium hyaluronate as the viscoelastic solution. Also, drugs for treating glaucoma, steroids, anti-angiogenesis (e.g., anti-vascular endothelial growth factor (anti-VEGF) antibodies and derivatives), anti-inflammatory drugs, or anti-fibrogenic drugs may be combined with the viscoelastic solution. These drugs may also be delivered alone without the viscoelastic solution if desired.

[0016] When delivering a fluid composition, the delivering step may include actuating the drive assembly such that retraction of at least a portion of the gear (or reversal of gear motion) pressurizes the reservoir by an amount sufficient to force the fluid composition through the lumen of the elongate member. The fluid composition may be delivered to dilate Schlemm's canal. The fluid composition may also be delivered to reduce intraocular pressure or to treat a medical condition such as glaucoma.

[0017] The systems, devices, and methods described herein may also use various degrees of force to disrupt trabecular tubule tissue, e.g., the trabecular meshwork, proximal tubule tissue, the Schlemm's canal wall, septa, obstructions, or stenoses within Schlemm's canal, and collector channels to improve drainage of aqueous humor and thereby reduce intraocular pressure and treat ocular conditions. The disruption force may be generated by non-implantable methods, e.g., delivering a disruption volume of viscoelastic fluid that may enlarge the canal and collector channels and tension the trabecular meshwork, by advancing a disruption instrument, e.g., a cannula, conduit, catheter, dilation probe, balloon, etc., which may or may not include one or more disruption components on its distal end, or both. Depending on factors such as the type or severity of the condition being treated, the disruption force may be generated to partially cut, tear, stretch, dilate, disrupt, or completely disrupt and / or remove the trabecular meshwork and / or nearby tubular tissue, and may be adjusted by varying the volume of viscoelastic fluid delivered or by varying the device configuration, as discussed further below.

[0018] The viscoelastic fluid or aqueous humor may be delivered using an integrated system controlled by a single operator with one hand. Advancement of the disruption instrument may also be provided by an integrated system controlled by a single operator with one hand. "Integrated" means that one system is used to advance the elongated member through at least a portion of Schlemm's canal and, in some instances, to deliver the viscoelastic fluid, instrument, or implant to Schlemm's canal. "Single operator controlled" means that all features of the system, such as advancement and retraction of the cannula, elongated member, and instrument, intraocular device delivery, fluid delivery, etc., may be performed by a single user. This is in contrast to other systems that use forceps for advancing the delivery catheter into Schlemm's canal and / or devices that are separate or independent of the delivery catheter and require an assistant(s) to tether to the delivery catheter while the surgeon holds the delivery catheter during the procedure. Following delivery of the disruption volume of fluid or device, an implant, e.g., a helical support or scaffold, may be advanced into Schlemm's canal to maintain its patency or energy may be delivered to alter the structure of Schlemm's canal and / or the surrounding trabecular tubule tissue.

[0019] A single operator, single handed controlled system for delivering fluid may include a cannula; an elongate member having a lumen, slidably disposed within the cannula, and advanceable distally from the cannula; and a handle coupled to the cannula, a portion of the handle defining a fluid reservoir, the handle operable with one hand to deliver fluid from the reservoir through the lumen of the elongate member.

[0020] Alternatively, a system for delivering a viscoelastic fluid may include a cannula; an elongate member having an internal lumen, slidably disposed within the cannula, and advanceable distally from the cannula; a handle coupled to the cannula, a portion of which defines a fluid reservoir; and a linear gear movable to advance fluid from the fluid reservoir through the lumen of the elongate member.

[0021] The system for delivering a viscoelastic fluid may also be configured to include a combination handle having a proximal end and a distal end; a cannula extending from the distal end and having a proximal portion and a distal portion; a slidable elongated member with a lumen disposed within the cannula; a housing having an inner surface and an upper surface and a lower surface; and a wheeled drive assembly extending beyond the upper and lower surfaces of the housing. Such a system with a combination handle may further include a rotating cannula that may be rotated, for example, from a left position to a right position, and a wheeled drive assembly with a single wheel (rotating component) configured to slide the elongated member. Instead of a wheel, a button, a slider, a foot pedal, or a motorized mechanism may also be configured to slide the elongated member.

[0022] In all variations of the viscoelastic fluid delivery system, the elongate member may comprise an internal lumen and may have an outer diameter ranging from about 25 microns to about 1000 microns, about 25 microns to about 500 microns, about 50 microns to about 500 microns, about 150 microns to about 500 microns, about 200 microns to about 500 microns, about 300 microns to about 500 microns, about 200 microns to about 250 microns, or about 180 microns to about 300 microns. In some examples, it may be beneficial for the elongate member to have an outer diameter of about 240 microns. The elongate member may also have a distal end with a cutout that is configured as a half tube or with multiple openings spaced along its axial length.

[0023] In addition to disrupting Schlemm's canal and surrounding trabecular tubule tissue using a disruption volume of viscoelastic fluid, the outer diameter of the elongated member may be sized to disrupt these tissues. For example, an elongated member having an outer diameter in the range of about 200 microns to about 500 microns may be beneficial for disrupting tissue. Additionally, the distal portion of the elongated member may include disruption components, such as tissue-disrupting notches, hooks, barbs, balloons, or combinations thereof. However, the system may include both features, i.e., it may not be necessary to deliver a disruption volume of viscoelastic fluid and also have an elongated member sized for disruption. An elongated member configured for disruption of Schlemm's canal and surrounding tissue may be used alone to reduce intraocular pressure without delivering fluid. Such elongated members may or may not have an internal lumen. In some variations, the elongated member may be configured such that the body of the elongated member cuts or tears the trabecular meshwork when the system is removed from the eye. The elongate member may also be configured to include a balloon or to be inflatable or expandable to a size that will section tissue as it is advanced.

[0024] The handle of the viscoelastic fluid delivery system described herein may include a drive assembly that can cause the delivery of fluid from the reservoir through the lumen of the elongate member. The drive assembly may be a wheeled drive assembly that includes a rotating component or multiple rotating components. The reservoir may be pre-filled with the viscoelastic fluid. Exemplary viscoelastic fluids may include hyaluronic acid, chondroitin sulfate, cellulose, polymers, or salts, derivatives, or mixtures thereof. It may be beneficial to use sodium hyaluronate as the viscoelastic fluid.

[0025] In some examples, a system for introducing a fluid composition into Schlemm's canal described herein may include a housing, a cannula, a flexible elongate 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 flexible elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The reservoir may include the fluid composition, and the reservoir may be in fluid communication with the lumen of the flexible elongate member. The drive assembly may be configured to move the flexible elongate member from the extended position to the retracted position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible elongate member. In some variations, the system may further include a lock configured to resist movement of the reservoir relative to the housing. In some examples, the system may be configured to prevent movement of the flexible elongate member toward the extended position after the flexible elongate member has been retracted a certain cumulative distance. In some of these examples, the certain cumulative distance may be about 40 mm.

[0026] In some examples, the drive assembly may include a linear gear. Translation of the linear gear in a first direction may move the flexible elongate member toward the stored configuration and may deliver the fluid composition from the reservoir through the lumen of the elongate member. In some of these examples, translation of the linear gear in a second direction may move the flexible elongate member toward the extended configuration. The volume of the fluid composition delivered from the reservoir may correspond to the distance of movement of the flexible polymeric elongate member toward the extended configuration. In some variations, the drive assembly may further include a rotating component, the rotation of which may cause the linear gear to translate. In some examples, the volume of the fluid composition delivered from the reservoir may correspond to the distance of translation of the linear gear in the first direction.

[0027] Also described herein is a device for introducing a fluid composition into Schlemm's canal. The device may include a housing, a reservoir, a flexible polymeric elongate member, and a drive assembly. The reservoir may hold the fluid composition and may be located within the housing. The flexible polymeric elongate member may include a lumen in fluid communication with the reservoir. The drive assembly may be configured to deliver a volume of the fluid composition from the reservoir to Schlemm's canal through the lumen of the flexible polymeric elongate member and to translate the flexible polymeric elongate member a distance relative to the housing. The volume of the fluid composition delivered may be constant relative to the distance translated by the flexible elongate member. In some variations, the drive assembly may include a rotatable wheel, and the volume of the fluid composition delivered and the distance translated by the flexible polymeric elongate member may be constant relative to the amount of rotation of the wheel.

[0028] Implant-free methods for treating ocular conditions may include advancing an elongated member filled with a volume of viscoelastic fluid into Schlemm's canal and delivering the viscoelastic fluid to Schlemm's canal in a volume sufficient to disrupt trabecular tubule tissue to reduce intraocular pressure. However, implant-free methods for treating ocular conditions may not necessarily include delivery of a viscoelastic fluid. In these examples, the methods may include advancing an elongated member into Schlemm's canal, the elongated member having a diameter of about 200 to about 500 microns, and advancing, retracting, or removing the elongated member into Schlemm's canal disrupts the trabecular tubule tissue sufficiently to reduce intraocular pressure. In some examples, the methods may include removing the system from the eye and, in so doing, cutting or tearing the trabecular meshwork with the body of the elongated member.

[0029] Another method for treating an ocular condition may be a single-operator, single-handed method for introducing a viscoelastic fluid into Schlemm's canal, comprising advancing an elongated member filled with a volume of viscoelastic fluid into Schlemm's canal and delivering the viscoelastic fluid to Schlemm's canal, where delivery of the volume of viscoelastic fluid is accomplished by a single-handed system used by a single operator.

[0030] When a viscoelastic fluid is delivered in the manner described herein, the disruption volume can be about 2 μl (microliters) to about 16 μl (microliters), or about 2 μl to about 8 μl. In some variations of the present methods, the volume of fluid capable of disrupting the 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 certain instances, it may be beneficial to deliver a volume of about 4 μl of viscoelastic fluid. In yet further variations, the volume of fluid delivered ranges from about 1 μl per 360 degrees of the canal to about 50 μl per about 360 degrees of the canal. In yet further variations, the volume of fluid delivered ranges from about 0.5 μl per 360 degrees of the canal to about 500 μl per 360 degrees of the canal. The viscoelastic fluid may be delivered while the elongated member of the single-handed system is advanced clockwise, counterclockwise, or both from Schlemm's canal and / or while the elongated member is withdrawn from Schlemm's canal. The volume of viscoelastic fluid delivered may be constant with respect to the distance the elongated member travels, and the viscoelastic fluid may be delivered the same distance around Schlemm's canal as the elongated member advances around the canal. As previously described, the viscoelastic fluid may be delivered to disrupt Schlemm's canal and the surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid may cause disruption by dilating Schlemm's canal, increasing the porosity of the trabecular meshwork, stretching the trabecular meshwork, forming microcracks or perforations in the nearby tubule tissue, removing septa from Schlemm's canal, dilating collector channels, or a combination thereof. The elongated member may be filled with a viscoelastic fluid at the start of an ophthalmic procedure so that a single operator can use one hand to operate the system (e.g., advance and retract the elongated member or any associated instruments) and deliver fluid to the trabecular tissue.

[0031] The method may include advancing the elongate member around a 360 degree arc of Schlemm's canal, a 180 degree arc of Schlemm's canal, a 90 degree arc of Schlemm's canal, or other degrees of arc (e.g., around an arc between 5 degrees and 360 degrees). Advancement may occur from a single access point in Schlemm's canal or from multiple access points in the canal. The disclosed methods may also be used to treat a variety of conditions, including, but not limited to, glaucoma, pre-stage glaucoma, and ocular hypertension.

[0032] Also disclosed is a method for abinternotrabeculotomy and goniotomy using the systems and steps disclosed herein, which includes advancing a cannula at least partially through the anterior chamber of the eye, entering Schlemm's canal at a single access point using the cannula, and delivering a volume of viscoelastic fluid through a lumen of an elongated member slidable within and extendable from the cannula, sufficient to disrupt Schlemm's canal and surrounding trabecular canalicular tissue to reduce intraocular pressure. Another method that may be useful for treating an ocular condition includes entering Schlemm's canal using an elongated member extendable from a single operator-controlled handle that includes a fluid reservoir, and delivering a volume of viscoelastic fluid from the fluid reservoir through the lumen of the elongated member by increasing pressure within the fluid reservoir, the volume of viscoelastic fluid delivered being sufficient to disrupt Schlemm's canal and surrounding tissue structures to reduce intraocular pressure. Other methods for abinternotrabeculotomy and goniotomy may include cutting, tearing, and / or removing the trabecular meshwork without delivering a viscoelastic fluid. Such methods may employ an elongate member configured to mechanically tear or cut and remove the trabecular meshwork. In some methods, the elongate member is configured to mechanically tear or cut the trabecular meshwork when the delivery system is removed from the eye after advancing the elongate member into Schlemm's canal. In other methods, the elongate member may include a larger diameter, cutting feature, and / or implement along or at a distal portion of the elongate member. For example, if the trabecular meshwork is cut and removed, the conduit may pull the excised tissue back into the cannula during retraction.

[0033] The methods for treating an ocular condition described herein may include advancing an elongated member into Schlemm's canal and retracting the elongated member. The elongated member may comprise a lumen having a distal opening at a distal tip of the elongated member, and retracting the elongated member includes simultaneously delivering a fluid composition from the distal opening of the lumen. In some variations, both retracting the elongated member and delivering the fluid composition may be actuated by rotation of a wheel. In some examples, the elongated member may be advanced a first length around Schlemm's canal, and the fluid composition may be delivered the same first length around Schlemm's canal. In some of the methods described herein, the elongated member may be advanced about 180 degrees around Schlemm's canal in a first direction. Some of these methods may further include advancing the elongated member 180 degrees around Schlemm's canal in a second direction, and retracting the elongated member and simultaneously delivering the fluid composition from the distal opening of the lumen.

[0034] In some variations, methods described herein for delivering a fluid composition to Schlemm's Canal using a device comprising a reservoir, a plunger with a lumen and a proximal end, and a flexible elongate member with a lumen may include: the reservoir being in fluid communication with the lumen of the flexible elongate member via the lumen of the plunger, a proximal end of the plunger being slidably positioned within the reservoir, and moving the proximal end of the plunger proximally within the reservoir from an extended position to a depressed position within the reservoir, such that the plunger displaces the fluid composition from the reservoir. The displaced fluid composition may travel through the lumen of the plunger to the lumen of the flexible elongate member.

[0035] In other variations, a method described herein for treating an ocular condition using a delivery system comprising a housing, a drive mechanism comprising a first wheel having a portion extending from a first side of the housing and a second wheel having a portion extending from a second side of the housing, a cannula extending from a distal end of the housing, and a slidable elongate member slidably positioned within the cannula may include puncturing a trabecular meshwork of an eye with the cannula, moving a portion of the first wheel extending from the first side of the housing proximally to extend the slidable elongate member distally from a stored position within the cannula such that it advances around Schlemm's canal in a first direction, and moving a portion of the first wheel extending from the first side of the housing distally to retract the slidable elongate member proximally back to a stored position. In some variations, moving a portion of the first wheel extending from the first side of the housing distally may also deliver a fluid composition to Schlemm's canal. In some examples, the method may further include moving a portion of the second wheel extending from the second side of the housing proximally to extend the slidable elongate member distally from a stored position within the cannula such that it advances around Schlemm's canal in a second direction, and moving a portion of the second wheel extending from the second side of the housing distally to retract the slidable elongate member proximally back to the stored position. In some examples, moving a portion of the second wheel extending from the second side of the housing distally may also deliver a fluid composition to Schlemm's canal.

[0036] A method for disrupting the trabecular meshwork of an eye using a device including a cannula, a flexible instrument slidable within the cannula between a retracted position and an extended position within the cannula, and a drive assembly may include advancing the cannula through a corneal or scleral incision into the anterior chamber, piercing the trabecular meshwork of the eye with the cannula, extending the flexible instrument from the retracted position to the extended position, and retracting the cannula from the anterior chamber without retracting the flexible instrument. The drive assembly may be configured to advance the flexible instrument a first maximum distance without retracting and to limit the cumulative advancement of the flexible instrument 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.

[0037] In some variations, a method for disrupting the trabecular meshwork of an eye using a device including a cannula and a flexible instrument having a body and slidable within the cannula between a retracted position and an extended position within the cannula may include advancing the cannula through a corneal or scleral incision into the anterior chamber, puncturing the trabecular meshwork of the eye with a distal tip of the cannula, extending the flexible instrument from the retracted position to an extended position, and progressively tearing the trabecular meshwork with the body of the flexible instrument from a proximal end of the body to a distal end of the body.

[0038] The kits described herein may include a first device and a second device. The first device may include a housing, a cannula, a flexible polymeric elongate 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 flexible polymeric elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be 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 the reservoir may be in fluid communication with the lumen of the flexible polymeric elongate member. The drive assembly may be configured to move the flexible polymeric elongate member from the extended position to the retracted position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible polymeric elongate member.

[0039] The second device may also include a housing, a cannula, a flexible polymeric elongate member, and a drive assembly. The cannula may be attached to a distal end of the housing and may include a distal tip. The flexible polymeric elongate member may include a lumen and a distal end. The distal end may be slidable within the cannula between a retracted position and an extended position, the distal end being within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The drive assembly may be configured to move the flexible polymeric elongate member from the extended position to the retracted position. The second device may not include a reservoir.

[0040] In some variations, the kits described herein may include a device and a tray. The device may include a housing, a cannula, and a flexible polymeric elongate member. The cannula may be attached to a distal end of the housing and may include a distal tip. The flexible polymeric elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be 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 pinch points and a second set of pinch points, and the cannula may not contact the tray when the device is in the tray.

[0041] In some examples, the device may further include a drive assembly, and the drive assembly may be configured to advance the flexible polymer elongate member a first maximum distance without retraction. The device may be configured to limit the cumulative advancement of the flexible polymer elongate 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.

[0042] Described herein is a method of manufacturing a cannula for accessing Schlemm's canal. The method may include creating a bevel at a distal tip of the cannula, sharpening the cannula, and blunting a portion of the cannula. The distal tip of the cannula may include an inner circumferential edge and an outer circumferential edge, and the cannula may include a lumen therethrough. The bevel may traverse the lumen, and creating the bevel may create proximal and distal ends of the distal tip. Sharpening the cannula may include sharpening the distal end of the distal tip of the cannula to create a sharp puncture tip. Blunting a portion of the cannula may include blunting a portion of the inner circumferential edge or outer circumferential edge. In some variations, the cannula may include a hypodermic tube made of stainless steel, nitinol, or titanium.

[0043] In some variations, sharpening the distal end of the distal tip may include sharpening a portion of the outer surface and / or a portion of the outer periphery of the cannula. In some variations, the sharp puncturing tip may be configured to puncture the trabecular meshwork of the eye. In some examples, the sharp puncturing tip may comprise two beveled surfaces. In some of these examples, the angle between the two beveled surfaces may be between 50 degrees and 100 degrees.

[0044] In some examples, smoothing a portion of the inner or outer periphery edge may include smoothing the inner periphery edge at a proximal end of the distal tip. In some variations, smoothing a portion of the inner or outer periphery edge may include smoothing the outer periphery edge at a proximal end of the distal tip. In some examples, smoothing a portion of the inner or outer periphery edge may include smoothing both the inner and outer periphery edges at a proximal end of the distal tip. In some variations, smoothing a portion of the inner or outer periphery edge may include smoothing the inner periphery edge at a proximal end of the distal tip. In some examples, smoothing a portion of the inner or outer periphery edge may include smoothing the entire inner periphery edge and smoothing the outer periphery edge at a proximal end of the distal tip. In some of these variations or examples, smoothing may include abrasively spraying a soda medium.

[0045] In some variations, the manufacturing method may further include applying a protective covering to the sharp puncture tip prior to the smoothing step. In these variations, the sharp puncture tip may comprise a beveled surface, and the beveled surface may be covered by the protective covering.

[0046] In some examples, the method of manufacture 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 cannula. In some of these variations, passivating may remove iron oxide from the cannula. Additionally, in some of these variations, passivating may include acid passivation. In some examples, the method may further include roughening at least a portion of the cannula proximal to the distal tip. In some of these examples, roughening may include abrasively spraying a soda medium.

[0047] In variations of the manufacturing methods described herein, the methods may further include cutting the cannula to a length of 50 mm to 70 mm. In some of these variations, cutting the cannula may include cutting the cannula to a length of 60 mm.

[0048] In some examples, the method may further include bending a distal portion of the cannula along a longitudinal axis of the cannula. In some of these examples, bending the distal portion of the cannula may include bending the distal portion to an angle between 100 degrees and 125 degrees. In some of these examples, bending the distal portion of the cannula may include bending the distal portion to an angle of 118 degrees.

[0049] In some variations, a method of manufacturing a cannula for accessing Schlemm's canal may include cutting the cannula to a working length, roughening an outer surface of the cannula, creating a bevel at the distal tip of the cannula, grinding the distal end of the distal tip, applying a protective cover, smoothing a portion of the cannula, bending the cannula, electropolishing the cannula, and passivating the cannula. In some variations, the cannula may comprise a proximal portion, a middle portion, a distal portion, and a lumen therethrough, and the distal portion may comprise a distal tip. In some examples, hardening the outer surface of the cannula may include roughening the outer surface of the middle portion of the cannula. In some variations, the distal tip of the cannula may comprise an inner periphery and an outer periphery, and the cannula may comprise a lumen therethrough. In some examples, the bevel may traverse the lumen, and creating the bevel may create the proximal and distal ends of the distal tip. In some variations, the distal end of the distal tip may be sharpened to further sharpen the distal end of the distal tip to create a sharp puncture tip. In some examples, applying a protective covering may include applying a protective covering to the sharp puncture tip, and smoothing a portion of the cannula may include smoothing a portion of an inner or outer periphery. In some variations, bending the cannula may include bending a distal portion of the cannula along a longitudinal axis of the cannula, and electropolishing the cannula may include electropolishing the distal tip. In some examples, passivating the cannula may include passivating the cannula with an acid. The present invention provides, for example, the following: (Item 1) 1. A system for introducing a fluid composition into Schlemm's canal, comprising: Housing and a cannula attached to a distal end of the housing and having a distal tip; a flexible elongate member having 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 being within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position; a reservoir containing a fluid composition, the reservoir being in fluid communication with the lumen of the flexible elongate member; a drive assembly configured to move the flexible elongate member from the extended position to the retracted position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible elongate member. (Item 2) Item 10. The system of item 1, further comprising a lock configured to resist movement of the reservoir relative to the housing. (Item 3) 2. The system of claim 1, wherein the drive assembly comprises a linear gear, and translation of the linear gear in a first direction moves the flexible elongate member toward the stored configuration and delivers the fluid composition from the reservoir through the lumen of the flexible elongate member. (Item 4) 4. The system of claim 3, wherein translation of the linear gear in a second direction moves the flexible polymer elongate member toward the extended configuration. (Item 5) 4. The system of claim 3, wherein the drive assembly further comprises a rotary component, rotation of the rotary component causing translation of the linear gear. (Item 6) 4. The system of claim 3, wherein a volume of the fluid composition delivered from the reservoir corresponds to a distance of translation of the linear gear in the first direction. (Item 7) 5. The system of claim 4, wherein the volume of fluid composition delivered from the reservoir corresponds to the distance of movement of the flexible elongate member toward the extended configuration. (Item 8) 2. The system of claim 1, wherein the device is configured to prevent movement of the flexible polymeric elongate member toward the extended position after the flexible elongate member has been retracted a certain cumulative distance. (Item 9) 9. The system of claim 8, wherein the constant cumulative distance is about 40 mm. (Item 10) 1. A system for introducing a fluid composition into Schlemm's canal, comprising: Housing and a reservoir positioned within the housing for holding the fluid composition; a flexible polymeric elongated member having an internal lumen in fluid communication with the reservoir; and a drive assembly configured to deliver a volume of a fluid composition from the reservoir to Schlemm's canal via the internal lumen of the flexible polymeric elongated member and to translate the flexible polymeric elongated member a distance relative to the housing; The system, wherein the volume of the delivered fluid composition is constant relative to the distance translated by the flexible polymeric elongate member. (Item 11) Item 11. The system of item 10, wherein the drive assembly comprises a rotatable wheel, and the volume of the delivered fluid composition and the distance translated by the flexible polymeric elongate member are constant relative to the amount of rotation of the wheel. (Item 12) 1. A method for treating an ophthalmic condition, comprising: advancing an elongate member into Schlemm's canal, the elongate member comprising a lumen having a distal opening at a distal tip of the elongate member; and retracting the elongate member while simultaneously delivering a fluid composition from the distal opening of the lumen. (Item 13) Item 13. The method of item 12, wherein both the retraction of the elongate member and the delivery of the fluid composition are actuated by rotation of a wheel. (Item 14) Item 13. The method of item 12, wherein the elongate member is advanced a first length around Schlemm's canal and the fluid composition is delivered the same first length around Schlemm's canal. (Item 15) Item 13. The method of item 12, wherein the elongate member is advanced approximately 180 degrees around Schlemm's canal in a first direction. (Item 16) advancing the elongated member in a second direction about 180 degrees around Schlemm's canal; 16. The method of claim 15, further comprising simultaneously retracting the elongate member and delivering a fluid composition from the distal opening of the lumen. (Item 17) 1. A method for delivering a fluid composition to Schlemm's canal using a device comprising a reservoir, a plunger having a lumen and a proximal end, and a flexible elongate member having a lumen, wherein the reservoir is in fluid communication with the lumen of the flexible elongate member via the lumen of the plunger, and the proximal end of the plunger is slidably positioned within the reservoir; moving the proximal end of the plunger proximally within the reservoir from an extended position to a depressed position within the reservoir such that the plunger displaces a fluid composition from the reservoir; The method, wherein the displaced fluid composition travels through the lumen of the plunger and into the lumen of the flexible elongate member. (Item 18) 1. A method for treating an ocular condition using a delivery system comprising: a housing; a drive mechanism including a first wheel having a portion extending from a first side of the housing and a second wheel having a portion extending from a second side of the housing; a cannula extending from a distal end of the housing; and a slidable elongate member slidably positioned within the cannula, comprising: puncturing the trabecular meshwork of the eye with the cannula; moving the portion of the first wheel extending from the first side of the housing proximally to extend the slidable elongate member distally from a stored position within the cannula such that it advances around Schlemm's canal in a first direction; and distally moving the portion of the first wheel extending from the first side of the housing to retract the slidable elongate member proximally back to the retracted position. (Item 19) 20. The method of claim 18, wherein distally moving the portion of the first wheel extending from the first side of the housing also delivers a fluid composition to Schlemm's canal. (Item 20) moving the portion of the second wheel extending from the second side of the housing proximally to extend the slidable elongate member distally from the stored position within the cannula such that it advances around Schlemm's canal in a second direction; 20. The method of claim 18, further comprising: moving the portion of the second wheel extending from the second side of the housing distally to retract the slidable elongate member proximally back to the retracted position. (Item 21) 21. The method of claim 20, wherein distally moving the portion of the second wheel extending from the second side of the housing also delivers a fluid composition to Schlemm's canal. (Item 22) 1. A method for disrupting a trabecular meshwork of an eye using a device comprising a cannula, a flexible instrument slidable within the cannula between retracted and extended positions within the cannula, and a drive assembly, comprising: advancing the cannula through a corneal or scleral incision into the anterior chamber; puncturing the trabecular meshwork of the eye with the cannula; extending the flexible instrument from the retracted position to the extended position; and retracting the cannula from the anterior chamber without retracting the flexible instrument; The method, wherein the drive assembly is configured to advance the flexible instrument a first maximum distance without retracting and configured to limit the cumulative advancement of the flexible instrument to a maximum total distance. (Item 23) 23. The method according to item 22, wherein the first maximum distance is 15 mm to 25 mm, and the maximum total distance is 35 mm to 45 mm. (Item 24) 1. A method for disrupting a trabecular meshwork of an eye using a device comprising a cannula and a flexible instrument having a body and slidable within the cannula between a retracted position within the cannula and an extended position, comprising: advancing the cannula through a corneal or scleral incision into the anterior chamber; puncturing the trabecular meshwork of the eye with a distal tip of the cannula; extending the flexible instrument from the retracted position to the extended position; and progressively tearing the trabecular meshwork with the body of the flexible instrument from a proximal end of the body to a distal end of the body. (Item 25) A kit comprising: A first device, Housing and a cannula attached to the distal end of the housing and having a distal tip; a flexible polymeric elongate member having 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 being within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position; a reservoir containing a fluid composition, the reservoir being in fluid communication with the lumen of the flexible polymeric elongate member; a drive assembly configured to move the flexible polymeric elongate member from the extended position to the retracted position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible polymeric elongate member; and a second device, Housing and a cannula attached to the distal end of the housing and having a distal tip; a flexible polymeric elongate member having 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 being within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position; a drive assembly configured to move the flexible polymer elongate member from the extended position to the retracted position; and The kit, wherein the second device does not include a reservoir. (Item 26) A kit comprising: a device comprising: a housing; a cannula attached to the distal end of the housing and having a distal tip; and a flexible polymeric elongate member having 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 being within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position; and a tray configured to removably receive the device, the tray comprising a first set of pinch points and a second set of pinch points, such that the cannula does not contact the tray when the device is in the tray. (Item 27) 27. The kit of claim 26, wherein the device further comprises a drive assembly, the drive assembly configured to advance the flexible polymer elongate member a first maximum distance without retraction and configured to limit cumulative advancement of the flexible polymer elongate member to a maximum total distance. (Item 28) Item 28. The method according to item 27, wherein the first maximum distance is 15 mm to 25 mm, and the total maximum distance is 35 mm to 45 mm. (Item 29) 1. A method of manufacturing a cannula for accessing Schlemm's canal, comprising: creating a bevel at a distal tip of the cannula, the distal tip having an inner periphery and an outer periphery, the cannula having a lumen therethrough, the bevel traversing the lumen, creating the bevel creating a proximal end and a distal end of the distal tip; The method includes sharpening the distal end of the distal tip to create a sharp puncture tip, and smoothing a portion of the inner or outer periphery. (Item 30) 30. The method of claim 29, wherein sharpening the distal end of the distal tip comprises sharpening a portion of an exterior surface and / or a portion of the outer periphery of the cannula. (Item 31) 30. The method of claim 29, wherein the sharp puncturing tip is configured to puncture the trabecular meshwork of the eye. (Item 32) 30. The method of claim 29, wherein the sharp puncture tip comprises two beveled surfaces. (Item 33) 30. The method according to item 29, wherein the angle between the two inclined surfaces is between 50 degrees and 100 degrees. (Item 34) 30. The method of claim 29, wherein smoothing the inner circumferential edge or a portion of the outer circumferential edge comprises smoothing the inner circumferential edge at the proximal end of the distal tip. (Item 35) 30. The method of claim 29, wherein smoothing a portion of the inner or outer circumferential edge comprises smoothing the outer circumferential edge at the proximal end of the distal tip. (Item 36) 30. The method of claim 29, wherein smoothing a portion of the inner or outer circumferential edge comprises smoothing both the inner and outer circumferential edges at the proximal end of the distal tip. (Item 37) 30. The method of claim 29, wherein smoothing the inner circumferential edge or a portion of the outer circumferential edge comprises smoothing the inner circumferential edge at the distal end of the distal tip. (Item 38) 30. The method of claim 29, wherein smoothing the inner periphery or a portion of the outer periphery includes smoothing the entire inner periphery and smoothing the outer periphery at the proximal end of the distal tip. (Item 39) Item 39. The method of item 38, wherein smoothing comprises abrasively spraying soda media. (Item 40) 30. The method of claim 29, wherein the smoothing comprises abrasively spraying soda media. (Item 41) 30. The method of claim 29, further comprising applying a protective covering to the sharp puncture tip prior to the smoothing step. (Item 42) Item 42. The method of item 41, wherein the sharp puncture tip comprises a bevel, and the bevel is covered by the protective cover. (Item 43) 30. The method of claim 29, further comprising polishing the distal tip. (Item 44) Item 44. The method of item 43, wherein the polishing comprises electropolishing. (Item 45) 30. The method of claim 29, further comprising passivating the cannula. (Item 46) 46. ​​The method of claim 45, wherein passivating removes iron oxide from the cannula. (Item 47) 46. ​​The method of claim 45, wherein passivating comprises passivating with an acid. (Item 48) 30. The method of claim 29, further comprising roughening at least a portion of the cannula proximal to the distal tip. (Item 49) Item 49. The method of item 48, wherein the roughening comprises abrasively spraying soda media. (Item 50) 30. The method of claim 29, further comprising cutting the cannula to a length of 50 mm to 70 mm. (Item 51) 51. The method of claim 50, wherein cutting the cannula comprises cutting the cannula to a length of 60 mm. (Item 52) 30. The method of claim 29, further comprising bending a distal portion of the cannula along a longitudinal axis of the cannula. (Item 53) Item 53. The method of item 52, wherein bending the distal portion of the cannula comprises bending the distal portion to an angle of 100 to 125 degrees. (Item 54) 54. The method of claim 53, wherein bending the distal portion of the cannula comprises bending the distal portion to an angle of 118 degrees. (Item 55) 30. The method of claim 29, wherein the cannula comprises a stainless steel, nitinol, or titanium hypodermic tube. (Item 56) 1. A method of manufacturing a cannula for accessing Schlemm's canal, comprising: cutting a cannula to a working length, the cannula comprising a proximal portion, a middle portion, a distal portion, and a lumen therethrough, the distal portion comprising a distal tip; roughening an exterior surface of the central portion of the cannula; creating a bevel at a distal tip of the cannula, the distal tip having an inner periphery and an outer periphery, the cannula having a lumen therethrough, the bevel traversing the lumen, creating the bevel creating a proximal end and a distal end of the distal tip; further sharpening the distal end of the distal tip by sharpening the distal end of the distal tip to create a sharp puncture tip; applying a protective cover to the pointed puncture tip; smoothing a portion of the inner or outer periphery; bending the distal portion of the cannula along a longitudinal axis of the cannula; electropolishing the distal tip; and passivating the cannula with an acid. [Brief description of the drawings]

[0050] [Figure 1] 1 shows a stylized cross-sectional view of the eye and some of the structures involved in the flow of aqueous humor out of the eye. [Diagram 2] 1 shows a perspective view of an exemplary delivery system for implanting an intraocular device. [Diagram 3] 1 illustrates a side view of an exemplary cannula of a delivery system. [Figure 4A] 4A and 4B show perspective views of an exemplary drive assembly in a handle of the system in a first orientation and in a second, inverted orientation, respectively. [Figure 4B] 4A and 4B show perspective views of an exemplary drive assembly in a handle of the system in a first orientation and in a second, inverted orientation, respectively. [Figure 5A] 1 shows a perspective view of an exemplary engagement mechanism for delivery of an illustrative ocular implant. [Figure 5B] 1 shows a perspective view of an exemplary engagement mechanism for delivery of an illustrative ocular implant. [Figure 6] 1 shows a perspective view of an engagement mechanism for delivery of an illustrative ocular implant according to one variation. [Figure 7A] 13 shows a perspective view of an illustrative engagement mechanism for delivery of an ocular implant according to another variation. [Figure 7B]13 shows a perspective view of an illustrative engagement mechanism for delivery of an ocular implant according to another variation. [Figure 8A] 13 shows a perspective view of an illustrative engagement mechanism for delivery of an ocular implant according to yet a further variation. [Figure 8B] 13 shows a perspective view of an illustrative engagement mechanism for delivery of an ocular implant according to yet a further variation. [Figure 9] 13 shows a perspective view of another exemplary engagement mechanism for delivery of an illustrative ocular implant. [Figure 10A] 10A and 10B show an exemplary delivery system for delivering a fluid composition to Schlemm's canal, respectively, in a perspective view and a partial cross-sectional view of the system. [Figure 10B] 10A and 10B show an exemplary delivery system for delivering a fluid composition to Schlemm's canal, respectively, in a perspective view and a partial cross-sectional view of the system. [Figure 11A] 1 illustrates an exemplary method of delivering a fluid composition from the delivery system. [Figure 11B] 1 illustrates an exemplary method of delivering a fluid composition from the delivery system. [Figure 11C] 1 illustrates an exemplary method of delivering a fluid composition from the delivery system. [Figure 12] 1 illustrates an exemplary slidable elongate member for delivering a fluid composition. [Figure 13A] 13A-13C show side and perspective views of a slidable elongate member according to another variation. [Figure 13B] 13A-13C show side and perspective views of a slidable elongate member according to another variation. [Figure 13C] 13A-13C show side and perspective views of a slidable elongate member according to another variation. [Figure 14] 1 is a stylized depiction of an abinterno technique for accessing Schlemm's canal with a cannula of an exemplary delivery system. [Figure 15] 1 illustrates an exemplary cannula according to another variation. [Figure 16]1 is a stylized depiction of the Abinterno technique of accessing Schlemm's canal from a single point and delivering a viscoelastic fluid while advancing a fluid delivery elongate member along a 360 degree arc of the canal. [Figure 17] FIG. 1 is a stylized depiction of the Abinterno technique of accessing Schlemm's canal from a single point and delivering a viscoelastic fluid while advancing a fluid delivery elongate member in both clockwise and counterclockwise directions along a 180 degree arc of the canal. [Figure 18A] 1 illustrates an exemplary abinterno technique for cutting or tearing the trabecular meshwork. [Figure 18B] 1 illustrates an exemplary abinterno technique for cutting or tearing the trabecular meshwork. [Figure 18C] 1 illustrates an exemplary abinterno technique for cutting or tearing the trabecular meshwork. [Figure 19] 1 is a flow chart illustrating an exemplary manufacturing method for a cannula that may be used with the devices, systems, and methods described herein. [Figure 20] 13A-13C are perspective views of variations of the distal tip of the cannula. [Figure 21A] 13A and 13B are perspective and front views, respectively, of a variation of the distal tip of the cannula. [Figure 21B] 13A and 13B are perspective and front views, respectively, of a variation of the distal tip of the cannula. [Figure 22A] 22C shows a perspective view of an exemplary drive assembly of the delivery system, FIG. 22D shows a perspective view of the delivery system with the slidable elongate member extended and without the top of the housing, FIG. [Figure 22B] 22C shows a perspective view of an exemplary drive assembly of the delivery system, FIG. 22D shows a perspective view of the delivery system with the slidable elongate member extended and without the top of the housing, FIG. [Figure 22C]22C shows a perspective view of an exemplary drive assembly of the delivery system, FIG. 22D shows a perspective view of the delivery system with the slidable elongate member extended and without the top of the housing, FIG. [Figure 22D] 22C shows a perspective view of an exemplary drive assembly of the delivery system, FIG. 22D shows a perspective view of the delivery system with the slidable elongate member extended and without the top of the housing, FIG. [Figure 23A] 23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 23B] 23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 23C] 23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 23D]23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 23E] 23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 23F] 23A shows a perspective view of an exemplary delivery system for delivering a fluid. FIG. 23B shows a cutaway view of the delivery system of FIG. 23A. FIGs. 23C-23D show perspective views of the delivery system of FIG. 23A without the housing. FIG. 23E shows a close-up cutaway view of the proximal end of the delivery system of FIG. 23A. FIG. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing, with the slidable elongate member extending out. [Figure 24] FIG. 2 shows a perspective view of another exemplary delivery system for delivering a fluid. [Figure 25A] A perspective view of an exemplary delivery system is shown with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cutaway views, respectively, of the lock rotated to allow filling of the reservoir. [Figure 25B] A perspective view of an exemplary delivery system is shown with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cutaway views, respectively, of the lock rotated to allow filling of the reservoir. [Figure 25C]A perspective view of an exemplary delivery system is shown with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cutaway views, respectively, of the lock rotated to allow filling of the reservoir. [Figure 25D] A perspective view of an exemplary delivery system is shown with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cutaway views, respectively, of the lock rotated to allow filling of the reservoir. [Figure 26A] An exemplary tray for a delivery system is shown in a perspective view with the delivery system (FIG. 26A) and with the delivery system and a filling tool (FIG. 26B). FIG. 26C shows an exploded view of an exemplary packaged kit. [Figure 26B] An exemplary tray for a delivery system is shown in a perspective view with the delivery system (FIG. 26A) and with the delivery system and a filling tool (FIG. 26B). FIG. 26C shows an exploded view of an exemplary packaged kit. [Figure 26C] An exemplary tray for a delivery system is shown in a perspective view with the delivery system (FIG. 26A) and with the delivery system and a filling tool (FIG. 26B). FIG. 26C shows an exploded view of an exemplary packaged kit. [Figure 27A] 1 shows an exemplary kit comprising multiple delivery systems. [Figure 27B] 1 shows an exemplary kit comprising multiple delivery systems. [Figure 28A] 28B-D are flow charts illustrating an exemplary method for delivering fluid to Schlemm's canal as part of the method of FIG. 28A when the slidable elongate member is retracted. [Figure 28B] 28B-D are flow charts illustrating an exemplary method for delivering fluid to Schlemm's canal as part of the method of FIG. 28A when the slidable elongate member is retracted. [Figure 28C]28B-D are flow charts illustrating an exemplary method for delivering fluid to Schlemm's canal as part of the method of FIG. 28A when the slidable elongate member is retracted. [Figure 28D] 28B-D are flow charts illustrating an exemplary method for delivering fluid to Schlemm's canal as part of the method of FIG. 28A when the slidable elongate member is retracted. [Figure 29A] 29B-D show a flow chart illustrating an exemplary method for disrupting the trabecular meshwork as part of the method of FIG. [Figure 29B] 29B-D show a flow chart illustrating an exemplary method for disrupting the trabecular meshwork as part of the method of FIG. [Figure 29C] 29B-D show a flow chart illustrating an exemplary method for disrupting the trabecular meshwork as part of the method of FIG. [Figure 29D] 29B-D show a flow chart illustrating an exemplary method for disrupting the trabecular meshwork as part of the method of FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0051] Systems and methods are described herein for accessing Schlemm's canal and for treating ocular conditions by delivering intraocular devices, instruments, and / or fluid compositions therein to reduce intraocular pressure. Fluids and certain components of the system, such as slidable elongate members, can be used to provide forces to disrupt trabecular tubule tissue, including trabecular meshwork, proximal tubule tissue, Schlemm's canal, and collector channels. As used herein, the term "disrupt" refers to the delivery of a volume of fluid or system components that alters tissue in a manner that improves flow through the trabecular outflow pathway. Examples of tissue disruption include, but are not limited to, dilating Schlemm's canal, dilating collector channels, increasing the porosity of the trabecular meshwork, stretching the trabecular meshwork, forming microscopic tears or perforations in proximal tubule tissue, removing septa from Schlemm's canal, cutting, tearing, or removing trabecular tubule tissue, or combinations thereof.

[0052] To better understand the systems and methods described herein, it may be useful to describe some of the basic ocular anatomy. FIG. 1 is a stylized depiction of a normal human eye. The anterior chamber (100) is shown bounded at its anterior surface by the cornea (102). The cornea (102) connects at its periphery to the sclera (104), a tough fibrous tissue that forms the white, protective shell of the eye. The trabecular meshwork (106) is located at the periphery of the anterior chamber (100). The trabecular meshwork (106) extends 360 degrees circumferentially around the anterior chamber (100). Schlemm's canal (108) is located on the periphery of the trabecular meshwork (106). Schlemm's canal (108) extends 360 degrees circumferentially around the trabecular meshwork (106). The anterior chamber angle (112) resides at the apex formed between the iris (110), the trabecular meshwork (106), and the sclera (104).

[0053] The system is generally configured for one-handed operation and control by a single operator and includes one or more features useful for easily accessing Schlemm's canal with minimal trauma. Once access to the canal is obtained, the system may deliver an intraocular device, an instrument, and / or a fluid composition. In some variations, the system advances an instrument that divides Schlemm's canal and surrounding tissue without delivery of an intraocular device or fluid composition. For example, the instrument may be an elongated member having an outer diameter sized to divide the canal and surrounding tissue and slidable within and extendable from a cannula used to access the canal. The body of the elongated member may, in some instances, be configured to cut or tear the trabecular meshwork when the system is removed from the eye while the elongated member is within Schlemm's canal, and / or may provide a dividing component at the distal end of the elongated member to assist in dividing the trabecular canal tissue.

[0054] When the device is implanted in the canal, it will generally be configured to maintain the patency of Schlemm's canal without significantly interfering with transmural fluid flow across the canal. This may restore, enable, or enhance normal physiological outflow of aqueous humor through the trabecular tubule tissue. An intraocular implant may be delivered, such as those disclosed in U.S. Pat. No. 7,909,789 and U.S. Pat. No. 8,529,622, each of which is incorporated herein by reference in its entirety. In some variations, the implants in U.S. Pat. No. 7,909,789 and U.S. Pat. No. 8,529,622 include a support having at least one fenestration that completely traverses the central core of Schlemm's canal without significantly interfering with transmural or longitudinal fluid flow across or along the canal. The intraocular device may also disrupt the proximal trabecular meshwork or adjacent inner wall of Schlemm's canal. The intraocular devices may also be coated with drugs useful for treating ocular hypertension, glaucoma or pre-glaucoma, infection, or scarring, neovascularization, fibrosis, or post-operative inflammation. The intraocular devices may also be formed to be solid, semi-solid, or bioabsorbable.

[0055] The system can also be used to deliver fluid compositions, such as saline or viscoelastic fluids. Saline can be used for irrigation. Viscoelastic fluids may be used in abinterno-type viscocanalostomy or canaloplasty procedures to disrupt the canal and surrounding tissue.

[0056] I. Systems / Devices The systems described herein may generally be single-operator, single-handed controlled devices that include a combined handle having a gripping portion and a housing having an inner end and a distal end. A cannula typically couples to and extends from the distal end of the housing. The cannula may include a proximal end and a distal curved portion, the distal curved portion having 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 a 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 generally include a drive assembly partially contained within the housing that includes a gear that converts rotational motion to linear motion. If an intraocular device is to be implanted in Schlemm's canal, the system may further include a slidable positioning element having proximal and distal ends disposed coaxially within the lumen of the cannula. The system may also be configured to include a slidable elongate member with a lumen disposed coaxially within the lumen of the cannula. If a fluid composition is to be delivered to Schlemm's canal, the system may also be configured to include a fluid assembly in the handle. Fluid compositions, such as saline, viscoelastic fluids including viscoelastic solutions, air, and gas, may be delivered using the system. Suitable markings, coloring, or indicators may be included on any portion of the system to aid in identifying the location or position of the distal end of the cannula, the positioning element, the engagement mechanism, the intraocular device, or the slidable elongate member. In some examples, the systems described herein may be used to perform abinterno trabeculotomy, abinterno transluminal trabeculotomy, clear corneal trabeculotomy, clear corneal transluminal trabeculotomy, abinterno tubuloplasty, and / or clear keratotubuloplasty, and may be used to deliver a fluid composition to the anterior or posterior segment of the eye.

[0057] An exemplary intraocular delivery system is shown in Figure 2. In this 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 cannula (212) is coupled to and extends from the housing distal end (210). A drive assembly (214) is substantially contained within the housing (206) that actuates movement of a positioning element (not shown). A port (216) is provided on the housing distal end (210) for removable connection to an irrigation fluid source.

[0058] The delivery systems described herein may, in some variations, be completely disposable. In other variations, portions of the delivery system may be reusable (e.g., non-patient contacting materials, such as the handle) while portions of the delivery system may be disposable (e.g., patient contacting materials, such as the cannula and elongate member). In yet other variations, the delivery systems described herein may be completely reusable.

[0059] General Purpose Handle The intraocular delivery systems described herein may include a universal handle that allows for one-handed use. For example, the handle may be configured to allow for left-handed or right-handed use, for left- or right-eyed use, 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 treated, or which direction around the canal the intraocular device, instrument, or fluid composition is delivered. For example, the delivery system may be used to deliver an intraocular device, elongated member, and / or fluid composition in a clockwise direction in the eye, and then, by simply flipping the handle to a second orientation (or in another variation, by rotating the cannula itself 180 degrees), it may be used to deliver the intraocular device, elongated member, and / or fluid composition in a counterclockwise direction. However, in other variations, it should be understood that the delivery systems described herein may be configured for use in a particular configuration (e.g., one side up, clockwise only, counterclockwise only, etc.). The handle generally includes a gripping portion and a housing. The gripping portion may be raised, recessed, grooved, or textured in certain areas to improve grip of the handle by the user or to improve user comfort. The housing may include an inner portion and a distal end. The inner portion of the housing may house the drive assembly and positioning elements (both of which are described further below). In some variations, the distal end of the housing includes a fluid port that may provide fluid for irrigation of the surgical field or for purging air from the system.

[0060] The universal handle may be made of any suitable material, including, but not limited to, fluoropolymers; thermoplastic materials, such as polyetheretherketone, polyethylene, polyethyleneterephthalate, polyurethane, nylon, and the like; and silicone. In some variations, the housing, or a portion thereof, may be made of a transparent material. Suitable transparent materials are typically polymers, such as acrylic copolymers, acrylonitrile butadiene styrene (ABS), polycarbonate, polystyrene, polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG), and styrene acrylonitrile (SAN). Acrylic copolymers that may be particularly useful include, but are not limited to, polymethylmethacrylate (PMMA) copolymers and styrene methylmethacrylate (SMMA) copolymers (e.g., Zylar 631® acrylic copolymer). In variations in which the universal handle is reusable, the handle may be made of a material that can be sterilized (e.g., by autoclaving), such as a heat-resistant metal (e.g., stainless steel, aluminum, titanium).

[0061] The length of the universal handle may generally be from about 1 inch (2.5 cm) to about 20 inches (50.8 cm). In some variations, the length of the universal handle may be from about 4 inches (10.2 cm) to about 10 inches (25.4 cm). In some variations, the length of the universal handle is about 7 inches (17.8 cm).

[0062] Cannula The cannula of the intraocular delivery system typically couples to and extends from the housing distal end and is generally configured to provide easy and minimally traumatic access to Schlemm's canal using a minimally invasive abinterno approach. The cannula may be fixedly attached to the distal end of the housing, or in other variations, rotatably attached to the distal end of the housing. In variations of the delivery system 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 a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end 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 pointed piercing tip, and an internal lumen extending from the proximal end through the distal tip. If 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 piercing tip may include one or more beveled surfaces, which are described in more detail below.

[0063] The cannula may be made of any suitable material with sufficient rigidity to allow it to be advanced through the eye wall and the anterior chamber. For example, the cannula may be formed of a metal, such as stainless steel, nickel, titanium, aluminum, or an alloy thereof (e.g., Nitinol metal alloy), a polymer, or a composite. Exemplary polymers include, but are not limited to, polycarbonate, polyetheretherketone (PEEK), polyethylene, polypropylene, polyimide, polyamide, polysulfone, polyether block amide (PEBAX), and fluoropolymers. In some instances, it may be advantageous to coat the cannula with a lubricious polymer to reduce friction between the ocular tissue and the cannula during the procedure. Lubricious polymers are well known in the art and include, but are not limited to, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, fluorinated polymers (including polytetrafluoroethylene (including PTFE or Teflon®)), and polyethylene oxide. In variations in which the cannula is reusable, the cannula may be made from a material that can be sterilized (eg, by autoclaving), such as a heat-resistant metal (eg, stainless steel, aluminum, titanium).

[0064] The cannula generally has an outer diameter sized to gain access to the lumen of Schlemm's canal while minimizing obstruction of the surgeon's field of vision. Thus, the outer diameter may range from about 50 microns to about 1000 microns. In some variations, the outer diameter may range from about 150 microns to about 800 microns. The cannula also has an inner diameter, which may range from about 50 microns to about 400 microns. The cannula may also be formed to have any suitable cross-sectional profile, such as circular, elliptical, triangular, square, rectangular, etc.

[0065] The cannula may be configured to include multiple parts or components. A cannula having a body, a distal curved portion having a proximal end and a distal end, a defined radius of curvature between the ends, and a bevel at the distal tip of the cannula that directly engages the distal end of the curved portion of the cannula may be particularly useful for accessing the lumen of Schlemm's canal. Here, the body (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 distal curved portion of the cannula may be uniform in cross-sectional shape or may be tapered closer to the distal end to facilitate entry into Schlemm's canal. The radius of curvature of the distal curved portion may be adapted to facilitate tangential entry and precise, minimally traumatic entry into Schlemm's canal and may range from about 1 mm to about 10 mm, or about 2 mm to about 5 mm. In one variation, the radius of curvature is about 2.5 mm. The cannula also has an angular span suitable for facilitating entry into Schlemm's canal, which may range from about 70 degrees to about 170 degrees, or from about 100 degrees to about 150 degrees. In one variation, the angular span is about 120 degrees.

[0066] The size, shape, geometry, etc. of the bevel at the distal end of the curved portion of the cannula can be beneficial in allowing easy and minimally traumatic access to Schlemm's Canal. In this regard, it can be particularly useful to have a bevel that directly engages the radius of curvature of the distal end of the cannula, as described in more detail below.

[0067] In other variations, the cannula may include a short straight segment that connects to the distal end of the distal curved portion of the cannula (e.g., at the end of the radius of curvature). Here, the bevel engages the straight segment rather than 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, e.g., about 0.1 mm, about 0.2 mm, about 0.3 mm, or about 0.4 mm. In variations in which the bevel directly engages the distal end of the curved portion of the cannula (i.e., the bevel directly engages the radius of curvature), the cannula lacks a straight segment (the length of the straight segment is zero).

[0068] It may also be useful to have a sharp, short bevel to minimize the distance any intraocular device must travel during implantation into the canal. Exemplary bevel angles may be from about 10 degrees to about 90 degrees. In some examples, the bevel angle may 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 may also be oriented in any suitable direction. For example, the bevel may be oriented so that it opens toward the surgeon, or flips over and opens away from the surgeon, or in any plane in between.

[0069] As described in more detail below, in some further variations, the cannula is configured to include one section that is sharp and another section that is blunt (e.g., deburred). Such a two-surface configuration of the cannula may be advantageous because it may provide easier access to the canal by puncturing the omentum while also providing a gentle, distributed force to the elongate member during retraction into the cannula to avoid cutting and breaking of the elongate member due to retraction forces. For example, as shown in FIG. 15, the distal end (1500) of the cannula may have a sharp piercing tip (1502) and a smooth edge (1504) that defines a portion of an opening (1506) through which a slidable elongate member (not shown) may be advanced and retracted. As described in more detail with reference to Figures 19, 20A-20B, and 21, the sharp tip (1502) may be formed by combining multiple bevels, and the smooth edge (1504) may be created by smoothing or deburring the inner and / or outer periphery of the distal tip. Additionally, in some embodiments, the inner and / or outer surfaces of the elongate member adjacent the opening (1506) may also be smooth. Methods of making the cannula are described in more detail below.

[0070] The cannula of the exemplary delivery system is shown in more detail in FIG. 3, where the cannula (300) comprises a proximal end (302), a distal curved portion (304), a body (314), and a distal tip (306). The distal curved portion (304) has a proximal end (308) and a distal end (310) and a radius of curvature (R) defined between these ends (308, 310). The distal curved portion (304) also has an inner radius (320) defined by a surface of the cannula closest to the center of the radius of curvature (R), and an outer radius (322) defined by a 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 curved portion of the cannula. In other words, the bevel (312) may be adjacent to the distal end (310) of the curved portion of the cannula. As previously discussed, this configuration of distal curved portion (304) and bevel (312) may be beneficial or advantageous to allow for easy, atraumatic, controlled access to Schlemm's canal. The angle of the bevel may also be important. Generally, a shorter bevel may be beneficial. The bevel (312) may comprise an angle (A) of about 5 degrees to about 85 degrees. In some variations, the angle (A) may be about 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) may be about 23 degrees to about 27 degrees. In the variation shown in FIG. 3, the bevel angle (A) is about 25 degrees.

[0071] FIG. 20 shows a perspective view of a distal tip (2002) of a cannula (2000) with a bevel (2014). The distal tip (2002) may be cut or sharpened 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 elliptical shaped lumen opening that is angled such that the top of the elliptical opening is closer to the proximal portion of the cannula than the bottom of the elliptical opening. Inner and outer periphery edges (2004, 2006) are also shown in FIG. 20.

[0072] 21A and 21B show perspective and front views, respectively, of a variation of a cannula distal tip (2100) comprising a bevel (2102) and a sharp piercing tip (2114). As shown therein, the distal tip (2100) also comprises a proximal end (2108), a distal end (2110), inner and outer periphery edges (2104, 2106), and a lumen opening (2112). The sharp piercing tip (2114) may comprise two beveled surfaces (2116) that meet to form a sharp point. The beveled surfaces (2116) may have any suitable angle that results in a sharp piercing tip (2114). For example, in some examples, the beveled surface (2116) may have an angle (B) relative to the longitudinal axis of the distal tip (2100) of about 20, 25, 30, 35, 40, 45, or 50 degrees, about 25 to about 50 degrees, or about 37.5 to about 42.5 degrees. In some examples, the angle (B) may be about 40 degrees. Thus, in some examples, the angle between the two beveled surfaces (2116) may be about 50 to about 100 degrees, and in some examples, the angle between the two beveled surfaces (2116) may be about 80 degrees. Although the distal tip (2100) is shown with two beveled surfaces, it should be understood that a distal tip with a single beveled surface may also be used.

[0073] Slender Members The delivery systems described herein may include a slidable elongate member disposed coaxially within a lumen of a cannula. The elongate members used with the systems described herein may be of various configurations and may or may not include a lumen. The elongate member may or may not be configured to deliver a fluid composition.

[0074] The elongated member may be coaxially disposed and slidable within the lumen of the cannula of the delivery system described herein. When the elongated member is in a retracted position relative to the cannula, the distal end of the elongated member may be located within (i.e., proximal to) the distal tip of the cannula. When the elongated member is in an extended position relative to the cannula, the distal end of the elongated member may be located outside (i.e., distal to) the distal tip of the cannula. The length of extension of the elongated member beyond the distal tip of the cannula may correspond to the distance around Schlemm's canal that the elongated member may traverse (e.g., to disrupt Schlemm's canal and / or surrounding trabecular tubule tissue and / or to deliver a fluid composition). In variations in which the delivery system is configured to deliver a fluid composition, the length traversed by the elongated member may correspond to the length of the circumference of Schlemm's canal to which the fluid composition is delivered. In variations in which the delivery system is configured to split or cut the trabecular meshwork, the length traversed by the elongate member may correspond to the length of the trabecular meshwork that is to be split or cut. In some variations, this length may be from about 1 mm to about 50 mm. In some of these variations, this length may be from about 10 mm to about 40 mm, from about 15 mm to about 25 mm, from about 16 mm to about 20 mm, from about 18 mm to about 20 mm, from about 19 mm to about 20 mm, from about 18 mm to about 22 mm, from about 20 mm, from about 30 mm to about 50 mm, from about 35 mm to about 45 mm, from about 38 mm to about 40 mm, from about 39 mm to about 40 mm, or about 40 mm. The elongate member may be moved between the extended and retracted positions using a drive assembly of the delivery system, as described in more detail below.

[0075] The elongated member may be sized such that it may be advanced through the cannula into a portion of Schlemm's canal (e.g., 0-360 degrees of the canal) to disrupt trabecular tubule tissue, stent, and / or apply tension to the canal, and / or deliver a fluid composition. The elongated member may be made from any suitable material that imparts the desired flexibility and pushability for introduction through the eye wall, access to Schlemm's canal, and / or orientation through other ocular tissue structures. For example, the elongated member may comprise a polymer (e.g., nylon, polypropylene); a polymer reinforced with metal wire, braid, or coil; a composite of polymer and metal; or a metal, such as stainless steel, titanium, a shape memory alloy (e.g., nitinol), or an alloy thereof. In variations in which the elongated member is reusable, the elongated member may be made from a material that can be sterilized (e.g., by autoclaving), such as a heat-resistant metal (e.g., stainless steel, aluminum, titanium). The elongate member may be straight with sufficient flexibility and pushability to orient Schlemm's canal in a ring shape, or may be preformed with a radius of curvature of about 2-10 mm or about 6 mm (i.e., the approximate radius of curvature of Schlemm's canal in an adult human) to more easily circumnavigate Schlemm's canal partially or entirely. In some variations, the elongate member may be configured to be advanced over or along a guidewire.

[0076] In some variations, it may be desirable for the elongate member to have one or more features to improve visualization of the elongate member. For example, the elongate member may be colored (e.g., red, orange, yellow, green, blue, purple, etc.). Additionally or alternatively, visualization may be improved using illuminated indicators, fiber optics, side-illuminating fiber optics, luminescence, fluorescence, or the like. For example, an optical fiber may travel along the body of the elongate member to deliver light to the distal tip of the elongate member to improve visualization of the distal tip of the elongate member as it is advanced or retracted around Schlemm's canal.

[0077] In some variations, the elongate member may be sized to have an outer diameter sufficient to disrupt Schlemm's canal and the surrounding trabecular tubule tissue. The outer diameter may range from about 25 microns to about 1000 microns, about 25 microns to about 500 microns, about 50 microns to about 500 microns, about 150 microns to about 500 microns, about 200 microns to about 500 microns, about 300 microns to about 500 microns, about 200 microns to about 250 microns, about 150 microns to about 200 microns, or about 180 microns to about 300 microns. In some examples, it may be beneficial for the elongate member to have an outer diameter of about 240 microns.

[0078] In some variations, the distal end of the elongate member may be configured as a blunt bevel, atraumatic tip, an enlarged atraumatic tip, or the like to aid in the advancement of the elongate member through Schlemm's canal. In some of these variations, the distal end may comprise a blunt umbrella-shaped atraumatic tip. In other variations, the distal portion of the elongate member may optionally include disruption components, such as notches, hooks, barbs, roughened surfaces, or combinations thereof, to disrupt Schlemm's canal or the proximal trabecular portion of the proximal trabecular meshwork. One or more protrusions emanating from the elongate member may further disrupt Schlemm's canal or the proximal trabecular portion of the proximal trabecular meshwork to increase the permeability of aqueous humor through the trabecular meshwork to Schlemm's canal. In some examples, the elongate member may also deliver energy to the trabecular canal tissue (e.g., ultrasonic energy, radio frequency energy (e.g., for electrocautery, electroablation), electromagnetic radiation, light energy (e.g., via fiber optics)).

[0079] In some examples, the elongate member may comprise a filament (e.g., a filament comprising nylon, polypropylene, metal, or the like). For example, the elongate member may comprise a nylon monofilament. An exemplary range of filament sizes may range from about 50 microns to about 300 microns. The filament may be configured to advance through all or a portion of Schlemm's canal. In some examples, the body of the filament may be configured to cut or tear the trabecular meshwork upon removal of the cannula from the eye. In other examples, the filament may be configured to disrupt the trabecular tubule tissue upon advancement into or retraction from Schlemm's canal. In still other examples, the filament may be configured to remain within the canal to continually deliver tension to the meshwork and maintain patency of the canal.

[0080] In some variations, the elongated member may comprise a lumen. For example, in one variation, the elongated member may comprise a microcatheter (e.g., a nylon microcatheter). In some of the examples in which the elongated member comprises a lumen, the elongated member may be configured to deliver a fluid composition. The fluid composition may travel through the lumen of the elongated member and may be delivered through an opening in the lumen. For example, as shown in FIG. 12, the elongated member (1200) may be a flexible tube having a lumen in fluid communication with an opening at the distal tip (1202). In some variations, the distal end of the elongated member may be configured or modified to aid in the delivery of the fluid composition to Schlemm's canal. For example, the distal end of the elongated member may comprise a cutout configured as a half tube. In addition to or as an alternative to an opening at the distal tip, the elongated member may optionally comprise a plurality of openings through its wall spaced along the axial length of the elongated member. In this variation, the fluid composition may be delivered from a reservoir through an opening in the elongated member to Schlemm's canal. This lateral drainage of fluid (e.g., viscoelastic fluid) may, in some instances, enhance disruption of outflow tissue and enhance aqueous humor permeability. It should be understood that the openings can be of any suitable number, size, and shape and can be spaced along the axial length of the elongate member (including the distal tip) in any suitable manner.

[0081] Drive Assembly The delivery system generally includes a drive assembly. The driver assembly of the delivery system is generally configured to move an ocular device, an elongate member, and / or a fluid composition into Schlemm's canal. The drive assembly, in some variations, may also be configured to position an ocular device within the canal, including advancing the device into the canal and retracting the device from the canal. The drive assembly may be at least partially contained within the housing and may include any suitable component or combination of components capable of providing a handle with versatile functionality.

[0082] The drive assembly may convert an 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 may cause the slidable elongate member to extend distally from the cannula and / or retract proximally into the cannula. The drive assembly may also optionally cause the fluid composition to be delivered from the reservoir through the elongate member and / or the cannula.

[0083] Two or more of these effects (i.e., extension of the slidable elongate member, retraction of the slidable elongate member, and / or delivery of the fluid composition) may be actuated using the same actuation mechanism. This may allow for one-handed use of the delivery system. For example, if the actuation mechanism comprises a rotatable element (such as one or more wheels, as in the variations described herein), rotating the rotatable element in a first direction may cause extension of the slidable elongate member, and rotating the rotatable element in a second direction may cause retraction of the slidable elongate member. If the delivery system is configured to deliver a fluid composition, rotating the rotatable element (e.g., in a second direction) may also cause delivery of the fluid composition. Delivery of the fluid composition may occur simultaneously with movement (e.g., retraction) of the slidable elongate member. In some of these examples, the fluid composition may be delivered to a portion of Schlemm's canal through which the slidable elongate member advances, which means that the fluid composition may be delivered at the same angle and length of Schlemm's canal as the extension of the elongate member. When the fluid composition occurs simultaneously with retraction of the elongate member, the fluid composition may displace the slidable elongate member as it is retracted and may expand Schlemm's canal and / or the collector channel at its location in Schlemm's canal. Furthermore, the amount of fluid delivered is related to the amount of movement of the elongate member, which means that a certain predetermined volume of the fluid composition may be delivered through the elongate member (e.g., delivered from the distal end of the elongate member) for a certain amount of movement of the elongate member (e.g., retraction distance) and for a certain amount of rotation of the rotatable element.

[0084] In some variations, the drive mechanism may be configured to allow for one-time use of the delivery system, that is, the drive mechanism may prevent re-extension of the slidable elongate member after a predetermined amount of extension and / or retraction, for example. Exemplary mechanisms that may translate an external input into movement of one or more components of the delivery system are described in more detail below.

[0085] In some variations, the drive assembly includes components that convert rotary motion to linear motion. For example, the drive assembly may include a linear gear and a pair of pinion gear mechanisms. The linear gear may have teeth on its surface that engage corresponding teeth on the pinion gear. Each of the pinion gear mechanisms may also couple to a rotating component (e.g., a wheel). Such coupling may be achieved with a pin that may be threaded through a central opening in the rotating component and the pinion gear, and a nut that secures the rotating component and pinion gear in a manner such that rotation of the rotating component rotates the pinion gear and vice versa. The wheels may be attached to the pinion gear, for example, by one of the following methods: 1) the wheels and pinion gear are molded as one piece using plastic injection molding techniques; 2) the wheels are slid onto the pinion gear and secured with adhesive; or 3) the wheels are slid onto the pinion gear and mechanically secured by fasteners or a "press fit" where the wheels are pressed onto the pinion gear and friction holds them fixed. In all of the described situations, the wheels and pinion gear may rotate coaxially, in the same direction, and at the same angular velocity. In some variations, each of the pinion gear mechanisms couples to at least two rotating components. In other variations, the drive assembly may be configured to include a single rotating component, multiple rotating components, or no rotating components. The wheels may have markings or coloring to indicate the degree of advancement or the direction of advancement.

[0086] One variation of a drive assembly useful for inclusion in a universal handle includes a linear gear, a pair of pinion gear mechanisms, and two rotating components coupled to each pinion gear (four rotating components total). In another variation, the drive assembly includes a linear gear and a single pinion gear mechanism with two associated wheels. In the variation with a pair of pinion gear mechanisms, the pinion gear mechanism and associated wheels may be disposed on either side of the linear gear. The pinion gear and the linear gear contact each other, that is, the teeth of the pinion gear may directly engage corresponding teeth on the linear gear, and the wheels on one side of the linear gear may contact the wheels on the other side of the linear gear. At least a portion of the wheels on either side of the linear gear may extend outside the housing. In this variation, the drive assembly may be operated with one hand when in a first configuration and then operated with the same or other hand when flipping to a second configuration. A drive assembly with such flexible capabilities can be easily used by both right and left handed surgeons and can be used in procedures where the handle is flipped during the procedure so that the cannula faces a first direction during a first portion of the procedure and a second direction during a second portion of the procedure. In a further variation, the drive assembly may include one rotating component on one side of the handle and a "universal" feature of the handle provided by the cannula that can itself rotate instead of flipping the handle.

[0087] In the variation shown in FIG. 4A, the delivery system (400) includes a drive assembly (402) having a linear gear (e.g., rack) (404) and a pair of pinion gear mechanisms (406). Both the linear gear and the pinion gear mechanisms have teeth that engage with each other to convert rotational motion (of the pinion gear mechanisms (406)) to linear motion (of the linear gears (404)). Each of the pinion gear mechanisms (406) is coupled to two rotatable components, shown in the figure as wheels (408), for a total of four rotatable components. The wheels (408) extend outside of the housing (414) of the delivery system (400) so that they can be rotated by one or more of the surgeon's fingers, correspondingly rotating the pinion gear mechanisms (406) to advance or retract the linear gears (404). The wheels (408) are coaxial with the pinion gear mechanism (406) and rotate in unison therewith. Movement of the linear gear (404) advances or retracts a positioning element (410) that is coaxially disposed and slidable within the cannula (412). Figure 4B shows the system of Figure 4A in a second, inverted orientation. In the orientation of Figure 4A, the cannula is oriented with the curvature pointing clockwise, while in the orientation of Figure 4B, the cannula is oriented with the curvature pointing counterclockwise. Having the wheels (408) extend outside the housing (414) on both sides may allow the delivery system (400) to be used in either orientation, with either hand, and with either eye of a patient. That is, the orientation of FIG. 4B may be used in the opposite or same hand as the orientation of FIG. 4A if a different direction of cannulation is desired (e.g., clockwise cannulation when counterclockwise cannulation is performed with the system in FIG. 4A).

[0088] Another variation of the drive assembly is shown in two different perspective views in FIGS. 22A-22B. As shown therein, the drive assembly (2202) may include a linear gear (e.g., rack) (2204) and a pair of pinion gear mechanisms (2206). Both the linear gear and the pinion gear mechanisms have teeth that engage with each other to convert rotational motion (of the pinion gear mechanisms) to linear motion (of the linear gears). More specifically, the linear gear (2204) may include teeth on both a first side (2220) and a second side (2222), with the teeth on the first side engaging with the first pinion gear mechanism and the teeth on the second side engaging with the second pinion gear mechanism. Each of the pinion gear mechanisms (2206) couples to two rotating components, shown in the figures as wheels (2208), for a total of four rotating components. The wheels (2208) are coaxial with the pinion gear mechanism (2206) and rotate in unison therewith. The drive assembly may include one or more features to stabilize the pinion gear mechanisms or otherwise keep them in place. For example, the drive assembly (2202) may include wheel spacers (2216) configured to seat between the axles (2218) of the pinion gear mechanisms. Rotation of the one or more wheels (2208) may cause translation of the linear gear (2204).

[0089] 22C and 23A-23B, the wheels (2208) may extend outside of the delivery system housing (2334) such that the wheels may be rotated by the surgeon to correspondingly rotate the pinion gear mechanism (2206) to advance or retract the linear gear (2204). The cannula (2344) may be slidable within the linear gear (2204) such that the cannula and wheels are fixed relative to each other and to the housing (2334), but the linear gear (2204) translates relative to the housing. The linear motion of the linear gear (2204) can be generated by the rotational motion of either of the two pinion gear mechanisms (2206), which in turn can be generated by the rotation of either of the wheels (2208) extending from the housing (2334), so that the delivery system (2300) can be easily operated using one hand with either the first side or the second side facing up, and therefore with the cannula (2344) facing in either the first direction or the second direction.

[0090] In other variations, one or both pinion gear mechanisms may be able to disengage from the linear gear by biasing their position off-axis from the linear gear. This action disengages the teeth of the pinion gear from the teeth of the linear gear, preventing movement of the linear gear. The pinion gear mechanisms may also be locked to prevent rotation by engaging intersecting pins or features that prevent rotation of the wheels.

[0091] Further variations of the drive assembly may not employ conversion of rotational motion to linear motion. For example, a slider (e.g., a finger slider) on the handle that is fixedly or removably coupled to a gear (e.g., a linear gear as described above) in the housing of the handle. Here, the drive assembly may be configured such that advancement or retraction of the slider causes advancement or retraction of the intraocular device and / or elongate member and / or delivery of the fluid composition to Schlemm's canal. In yet further variations, a button that can be pressed or pinched may be used instead of a slider, or a foot pedal may be used to deliver the intraocular device, instrument, and / or fluid composition.

[0092] Extending and Retracting the Elongated Member In some variations, the proximal end of the elongate member may be fixed relative to a portion of the drive assembly (e.g., linear gear (2204)), while the distal end may be slidably coaxial within the lumen of the cannula. If the elongate member does not include a lumen (e.g., is a filament), the elongate member may be attached to the drive assembly by crimping in some examples. If the elongate member includes a lumen, the elongate member may be fixedly attached (e.g., by adhesive) to the drive assembly in some examples to keep the lumen of the elongate member from becoming occluded. The cannula may be fixedly attached to the housing as well. In variations of the delivery system in which the handle is reusable and the cannula and elongate member are disposable, the disposable assembly with the elongate member pre-loaded within the cannula may be attached to the reusable handle by any suitable mechanism, such as threaded fasteners or snap-in features.

[0093] When a portion of the drive assembly moves proximally or distally within the housing, this may cause a corresponding movement of the elongated member relative to the cannula. That is, movement of a portion of the drive assembly toward the cannula (i.e., toward the distal end of the housing) may move the elongated member from a retracted position to an extended position, and movement of a portion of the drive assembly away from the cannula (e.g., toward the proximal end of the housing) may move the elongated member from an extended position to a retracted position. An example of an elongated member in an extended position is shown in FIGS. 22C-22D. As shown in the pictorial view in FIG. 22D with the top of the housing (2334) removed, the linear gear (2204) is in a distal position. Thus, the elongated member (2346) extends from the cannula (2344).

[0094] Storage The system generally includes a reservoir where the fluid composition is to be delivered to Schlemm's canal. The reservoir may contain various fluid compositions for delivery. Exemplary fluid compositions include saline and a viscoelastic fluid. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, derivatives 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 include a drug suitable for treating glaucoma, reducing or lowering intraocular pressure, reducing inflammation, and / or preventing infection, fibrosis, scarring, clotting, thrombosis, bleeding, or angiogenesis. Drugs such as antimetabolites, vasoconstrictors, anti-VEGF agents, steroids, heparin, anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), other anticoagulants, fibrinolytic compounds, biological agents, and gene therapy agents may also be delivered in combination with the viscoelastic composition. Examples of glaucoma drugs include prostaglandins, beta blockers, miotics, alpha adrenergic agonists, or carbonic anhydrase inhibitors. Anti-inflammatory drugs such as NSAIDs, corticosteroids, or other steroids may be used. Steroids such as prednisolone, prednisone, cortisone, cortisol, triamcinolone, or shorter acting steroids may be used. Examples of antimetabolite drugs include 5-fluorouracil or mitomycin C. Examples of drugs or antibodies that prevent angiogenesis include bevacizumab, ranibizumab, and others. In yet another variation, the system delivers only the drug without the viscoelastic composition. Saline solution may also be the fluid used. In yet another variation, the system may be configured to deliver gases such as, but not limited to, air, distensible gases (e.g., SF6, C3F8), and the like.

[0095] In some variations, the reservoir may be at least partially defined by the fluid assembly and housing, as well as the linear gear within the handle. The fluid assembly may be made from any suitable material as previously described for the cannula and housing. The volume (in microliters) of fluid contained within the reservoir 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.

[0096] The fluid composition may be pre-loaded in the reservoir so that the fluid can be delivered by a single device and a single user, or the reservoir may be loaded prior to use of the system, e.g., at the beginning of an ophthalmic procedure. Again, this is in contrast to other systems that use a forceps or other advancement instrument for advancing the fluid delivery catheter into Schlemm's canal, and / or a device containing a viscoelastic fluid that is separate or independent of the delivery catheter or catheter advancement instrument and must be tethered to the delivery catheter or catheter advancement instrument, e.g., by an assistant or by the surgeon's hand, while the delivery catheter or catheter advancement instrument is held by one hand of the surgeon during the procedure. For example, a loading component may be provided in the fluid assembly for transfer of the fluid composition to the reservoir. The loading component may have any suitable configuration that provides for reversible fixation of the fluid container, e.g., a syringe, cartridge, etc., to the system, and loading of the fluid composition into the reservoir. The loading component may be a luer fitting or may include a one-way valve.

[0097] An exemplary delivery system comprising a reservoir is shown in Figures 23A-23F. The delivery system (2300), shown with (Figures 23A, 23B, and 23E), without (Figures 23C and 23D), and partially without (Figure 23F), comprises a fluid assembly (2316) comprising a reservoir (2302). In an exemplary method, a fluid composition may be filled into the reservoir (2302) through a proximal opening (2328) and via a proximal seal (2318). As best shown in Figure 23E, a distal end of the reservoir (2302) may be formed by a plunger (2338) (described in more detail below) and a distal seal (2354).

[0098] The proximal seal (2318) may be a mechanical seal comprising a ball bearing (2324) located at the proximal end of the reservoir (2302) and spring-loaded against an o-ring or gasket (2330) to close and seal the reservoir. A filling tool (2326) (e.g., a nozzle) may be used to open the seal by compressing the ball bearing (2324) and moving the ball bearing (2324) proximally toward an open position. The fluid composition may be filled into the reservoir while the proximal seal (2318) is open. After filling with the fluid composition, the filling tool (2326) may be removed, allowing the ball bearing (2324) to return to its closed position. A close-up cross-sectional view in FIG. 23E shows the proximal opening (2328) and the ball bearing (2324). An O-ring or gasket (2330) seats between the ball bearing (2324) and the spring (2332) such that the force from the spring pushes the ball bearing into the gasket, forming a seal between the ball bearing and the gasket in the closed position. A filling tool (2326) is configured to fit into the proximal opening (2328) and compress the ball bearing (2324). A distally directed force on the ball bearing (2324) moves it distally to the open position, compressing the spring (2332) and creating an opening between the ball bearing and the gasket (2330) through which the fluid composition can flow. When the filling tool (2326) is removed from the proximal opening (2328), the spring (2332) pushes the ball bearing (2324) proximally back to the closed position.

[0099] It should be understood that in other variations, the reservoir may include other types of seals to allow for filling of the reservoir with the fluid composition. For example, FIG. 24 shows an alternative variation of a delivery system (2400) in which the seal includes a membrane (e.g., a silicone membrane). As shown, the fluid composition may be filled into the reservoir (after movement of optional lock (2404)) by piercing the membrane with a needle (2402) (e.g., a 25 gauge needle). In yet another variation, the delivery systems described herein may be configured to receive a pre-filled cartridge comprising the fluid composition. For example, the handle and fluid assembly may be configured such that a pre-filled cartridge may be inserted into the fluid assembly.

[0100] To fill the reservoir, it may be desirable to at least temporarily fix the fluid assembly in place to allow for application of a distal force to the seal. In some variations, the delivery system may include a lock configured to hold the fluid assembly in place while injecting the fluid composition into the reservoir. However, it should be understood that in other variations, the delivery system may not include a lock. In variations having a lock, it may be desirable for the lock to be detachable from the delivery system (or otherwise release the fluid assembly) to allow the fluid assembly to translate relative to the housing after filling the reservoir. As described in more detail herein, translation of the fluid assembly may allow for extension of the slidable elongate member and / or injection of the fluid composition during the procedure.

[0101] In variations of delivery systems having a lock, the lock may optionally further act as a cap to protect the distal opening to the reservoir. In these variations, the lock may comprise a first configuration in which it holds the reservoir in place and covers the proximal opening to the reservoir, and a second configuration in which it holds the reservoir in place but allows access to the proximal opening to the reservoir so that the reservoir may be filled with the fluid composition. In some examples, the lock may alternate from a first position to a second position.

[0102] 25A-25D illustrate an exemplary lock (2502). As shown therein, the lock (2502) may comprise a pin (2508) configured to fit into an opening (2504) in a handle (2506) of the delivery system (2500). In a first configuration, as shown in FIG. 25B, the lock (2502) may be inserted into the opening (2504) in the handle and cover the proximal opening (2510). The lock (2502) may comprise a protrusion (2518) configured to mate with the proximal opening (2510) to stabilize the lock in the first configuration. In a second configuration, as shown in FIGS. 25C-25D, the lock (2502) may remain inserted into the opening (2504) but may pivot within the opening to expose the proximal opening (2510) to allow filling of the reservoir (2512). When the pin (2508) is inserted into the opening (2504), the pin may limit movement of the reservoir (2512) relative to the housing. This may allow the filling instrument (2514) to apply a 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). Limiting movement of the reservoir (2512) relative to the handle (2506) may prevent movement of the reservoir, or other internal components of the delivery system, prior to use (e.g., during transport). Once filling of the reservoir (2512) is complete, the lock (2502) may be removed from the opening (2504), as shown in FIG. 25A, at which point the reservoir (2512) may no longer be restricted from movement relative to the housing by the lock.

[0103] Delivery of Fluid Compositions The delivery systems described herein may be configured to deliver fluid to Schlemm's canal. The fluid may be delivered in a volume that provides sufficient force to disrupt Schlemm's canal and the surrounding trabecular tubule tissue. Exemplary disruption 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 disruption volume of fluid may range from about 1 μl to about 50 μl, or from about 20 μl to about 50 μl.

[0104] As mentioned above, the elongate member may be coaxially disposed within the lumen of the cannula. In a variation of the delivery system configured to deliver the fluid composition, the elongate member may include a lumen. The lumen of the elongate member may be operatively coupled to a reservoir to deliver the fluid composition to Schlemm's canal. The elongate member generally has a proximal end, a distal end, and a wall that defines a lumen extending therethrough. However, in some examples, the delivery system lacks an elongate member conduit, and the fluid composition is delivered solely through the cannula. In other examples, two elongate members may be used, each of which is advanced through the canal in both a clockwise and counterclockwise direction simultaneously to more rapidly cannulate Schlemm's canal and deliver therapeutic agent.

[0105] When using the delivery system to deliver a fluid composition, the fluid composition may be pre-loaded into the reservoir of the system or may be loaded into the reservoir prior to use of the system. An exemplary delivery system for delivering a fluid composition to Schlemm's canal is shown in Figures 10A and 10B. Referring to Figure 10A, the delivery system (1000) includes a general-purpose handle (1002) having a gripping portion (1004) and a housing (1006). The housing (1006) has a proximal end (1008) and a distal end (1010). A cannula (1012) is coupled to and extends from the housing distal end (1010). A drive assembly (1014) is substantially contained within the housing (1006) that actuates movement of a slidable elongate member (not shown). The cannula (1012) and drive assembly (1014) have the same configuration as shown and described in Figures 3 and 4A-4B for the present system adapted for implantation of an intraocular device, and therefore will not be described in detail here.

[0106] The delivery system (1000) also includes a fluid assembly (1016) (shown in FIG. 10B) within the handle (1002) having a filling component (1018) configured to enable transfer of a fluid composition from an external source to a reservoir (1020) defined by the fluid assembly and linear gear. A slidable elongate member (1022) is coaxially disposed within the lumen of the cannula in fluid communication with the reservoir. As previously mentioned, in instrument-based systems that do not deliver implants or fluids, the system may not include a reservoir.

[0107] In an exemplary method, as illustrated by FIGS. 11A-11C, a fluid composition may be transferred to a reservoir (1102) of a system (1100) by filling through a filling component (1104). As shown in the drawings, 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 a lumen (1114) extending from the proximal end (1110) to the distal end (1112). The lumen (1114) is in fluid communication with a lumen (not shown) of a slidable elongate member (1118). To deploy the fluid composition from the reservoir (1102), the linear gear (1108) is retracted in the direction of the arrow (FIG. 11B) such that the reservoir (1102) is pressurized. Retraction may be accomplished by rotation of the pinion gear mechanism 1120. Once a sufficient amount of pressure is created in the reservoir 1102, the fluid composition contained therein is injected through the linear gear lumen 1114 and the lumen of the elongate member 1118 and into Schlemm's canal.

[0108] Here, any fluid delivered flows through the distal end (1202) to Schlemm's canal. In other variations, the slidable elongate member (1300) may be configured to include multiple openings spaced along its axial length. The openings may have any suitable shape, for example, slots (1302) (FIG. 13A) or circles (1304) (FIG. 13B). Fluid compositions delivered using the elongate members shown in FIGS. 13A and 13B may exit the elongate member partially through the openings and partially through the distal end of the elongate member. The distal end of the elongate member may also be configured as a half tube (1306) (FIG. 13C).

[0109] Some variations of the fluid assembly include a locking mechanism to prevent movement of the assembly within the handle, for example when the linear gear is advanced or retracted. The locking mechanism may comprise a ratchet pawl, a combination of ratchet pawls, or any other suitable mechanism that can be locked to prevent movement of the fluid assembly and unlocked to allow movement of the fluid assembly.

[0110] Referring back to FIGS. 23A-23F, another exemplary delivery system (2300) for delivering a fluid composition to Schlemm's canal shown therein may comprise a housing (2334) and a cannula (2344) extending from a distal end of the housing. The drive assembly (2202) (described above with respect to FIGS. 22A-22D) may be located within the housing (2334), as may the fluid assembly (2316) (described in more detail above). As described above, the drive assembly (2202) may comprise a linear gear (2204) and a pair of pinion gear mechanisms (2206) coupled to wheels (2208). The delivery system (2300) may comprise a slidable elongate member (2336). A proximal end of the elongate member may be fixed relative to the linear gear (2204), while a distal end of the elongate member may be slidably coaxially disposed within a lumen of the cannula (2334). The reservoir (2302) of the fluid assembly (2316) may be in fluid communication with the lumen of the elongate member. For example, a plunger (2338) having a lumen fluidly connects the reservoir (2302) to the lumen of the elongate member. A proximal end (2350) of the plunger (2338) may be slidably positioned within the reservoir (2302), and a distal end (2352) of the plunger may be fixedly attached to the linear gear (2204) of the drive assembly (2202).

[0111] The fluid assembly (2316) and the drive assembly (2202) may be connected by a linkage (2348), as best shown in FIG. 23D. (The delivery system (2300) is shown without the linkage assembly in FIG. 23A to better show the other components.) The linkage (2348) may be configured to allow the fluid assembly (2316) and the drive assembly (2202) to move as a unit, or may allow limited movement of the fluid assembly and drive assembly relative to one another. In some variations, the linkage (2348) may allow the fluid assembly (2316) to move closer to, but not far from, the drive assembly (2202). For example, as best shown in FIG. 23D, the proximal end (2340) of the linkage (2348) may be fixedly attached to the fluid assembly (2316). The distal end 2342 of the linkage 2348 may be attached to the linear gear 2204 of the drive assembly 2202 by a one-way ratchet. The distal end 2342 may be able to move distally along a track in the linear gear 2204, but teeth in the track may resist proximal movement of the distal end 2342 along the track. In this manner, the fluid assembly 2316 may be able to move distally toward the linear gear 2204 such that the fluid assembly and the linear gear move closer together (by shortening the portion of the linkage 2348 between the fluid assembly and the linear gear), but the fluid assembly may not be able to move proximally away from the linear gear. It should be understood that in other variations, the linkage may be fixedly attached to the linear gear and slidably attached to the fluid assembly.

[0112] In this manner, the linear gear (2204) and the fluid assembly (2316) may be movable relative to one another and within the housing (2334). Movement of the linear gear (2204) and the fluid assembly (2316) relative to one another and to the housing (2334) may cause one or more effects, including extension and retraction of the slidable elongate member and / or delivery of the fluid composition. More specifically, because a proximal end (2350) of the plunger (2338) may be slidably positioned within the reservoir (2302) and a distal end (2352) of the plunger may be fixedly attached to the linear gear (2204), movement of the reservoir closer to the linear gear may cause proximal movement of the plunger within the reservoir. This increases the length of the plunger (2338) located within the reservoir (2302). The portion of the plunger (2338) within the reservoir (2302) may displace fluid within the reservoir. The displaced fluid may travel distally through the lumen of the plunger (2338), through the lumen of the elongate member (2336), and be delivered from a distal opening of the lumen of the elongate member.

[0113] Additionally, as described above, movement of the linear gear (2204) relative to the housing (2334) may cause the slidable elongate member (2336) to extend or retract. The linear gear (2204) may be movable between a proximal portion and a distal portion by rotation of the wheels (2208), while the wheels (2208) remain fixed relative to the housing (2334). Because the proximal end of the elongate member is fixed relative to the linear gear (2204) and the distal end of the elongate member may be slidable within the lumen of the cannula (2344), when the drive assembly (2202) is in a proximal position, the elongate member may correspondingly be in a retracted position relative to the cannula (2344). When the elongate member is in the retracted position, the distal end of the elongate member may be located within the cannula (2344) (e.g., proximal to the distal tip of the cannula). When the drive assembly (2202) is in the distal portion, the elongate member may correspondingly be in an extended position relative to the cannula (2344). When the elongate member (2336) is in the extended position, the distal end of the elongate member may extend from the cannula (e.g., distal to the distal tip of the cannula).

[0114] Relative motion of the drive assembly (2202), fluid assembly (2316), and housing (2334) may thus be used to extend the slidable elongate member (2336) within Schlemm's canal and simultaneously retract the elongate member within Schlemm's canal and deliver fluid. The delivery system (2300) may begin in a configuration in which the fluid assembly (2316) and linear gear (2204) are separated over the entire length of the linkage (2348), with the fluid assembly located at the proximal end of the housing (2334) and the slidable elongate member in a retracted position within the cannula (2344). This configuration is shown in FIGS. 23A-23D. The wheel (2208) may rotate in a first direction to advance the linear gear (2204) distally within the housing (2334). The linkage (2348) moves the fluid assembly (2316) distally within the housing at an equal distance to maintain the separation between the fluid assembly and the linear gear (2204). As the linear gear (2204) advances, the elongated member (2336) may move from a retracted position to an extended position. This may move the elongated member (2336) through Schlemm's Canal. This configuration is shown in FIG. 23F, which shows the delivery system (2300) with the top of the housing (2334) removed to show the linear gear (2204) in a distal position. As can be seen there, the elongated member (2336) is in an extended position relative to the cannula (2344), and the fluid assembly (2316) is also in a distal position within the housing (2334).

[0115] The wheel (2208) may then rotate in a second direction to retract the linear gear (2204) proximally within the housing (2334). This may move the slidable elongate member (2336) from the extended position to the retracted position. However, the fluid assembly (2316) may not correspondingly move proximally within the housing (2334). The housing (2334) may include internal teeth (2446) near the fluid assembly (2316) that are configured to engage external teeth on the fluid assembly. These teeth may cause the fluid assembly (2316) to move distally within the housing (2334) but not move proximally within the housing. Thus, when the linear gear (2204) is retracted into the housing (2334), the fluid assembly (2316) may remain fixed relative to the housing. The linear gear (2204) and the fluid assembly (2316) thus move closer together and the linkage (2348) moves distally along a track in the linear gear (2204) to accommodate this motion. As the linear gear (2204) and the fluid assembly (2316) move closer together, the plunger (2338) may displace fluid within the reservoir (2302), as described in more detail above. The fluid may then travel through the lumen of the plunger (2338) and be delivered through the lumen (2336) of the elongate member.

[0116] In this manner, fluid may be delivered from the elongate member simultaneously as it is retracted. Fluid may replace the elongate member as it is retracted, such that fluid may be delivered to an angle and length of Schlemm's canal that is the same as the angle and length the elongate member was advanced to. A constant and predetermined volume of fluid may be delivered for a given amount of retraction of the elongate member due to displacement of fluid in the reservoir by the plunger, and retraction of the elongate member and delivery of the fluid composition may be accomplished by a single user motion (rotation of the wheel (2208)). In some examples, full retraction of the elongate member may result in delivery of about 2 μl to about 9 μl of fluid. In some of these examples, full retraction of the elongate member may result in delivery of about 4.5 μl of fluid. As the elongate member (2336) is retracted, the delivery system (2300) may produce an audible and / or tactile click increment. These clicks may be due to, for example, ratcheting of distal end (2342) of linkage (2348), which is distal to linear gear (2204). Each click may correspond to a fixed and predetermined volume of fluid, in some cases approximately 0.5 μl.

[0117] In some variations, the delivery system may be configured to allow for a certain cumulative amount of extension and / or retraction of the slidable elongate member. The certain cumulative amount of extension / retraction may correspond, for example, to a full circumference of Schlemm's canal, two full circumferences of Schlemm's canal, or any desired distance. Exemplary certain 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. Additionally or alternatively, the delivery system may be configured to allow for a certain cumulative delivery of fluid (e.g., in some variations, about 9 μl of fluid). For example, in the delivery system 2300, as described above, the fluid assembly 2316 may move distally within the housing 2334 but not proximally within the housing, and the fluid assembly may move toward the linear gear 2204 but not away from it. Thus, each extension of the slidable elongate member may move the linear gear 2204 and the fluid assembly 2316 distally, but each retraction of the elongate member may move the linear gear 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 may prevent the fluid assembly 2316 from moving distally beyond a certain point. Once the fluid assembly 2316 reaches its most distal portion, neither the fluid assembly nor the linear gear 2204 may move distally or proximally, and the wheel 2208 may not rotate any further. The distance between the initial position of the fluid assembly (2316) and its final, re-distal position may determine a certain cumulative amount of extension / retraction of the slidable elongate member and a certain cumulative delivery of fluid. However, it should be understood that other variations of delivery systems may not have a limited cumulative amount of extension and / or retraction of the elongate member. This means that some delivery systems may be able to repeatedly extend and retract without a certain limit.

[0118] It should be understood that the delivery system (2300) may advance and retract the slidable elongate member multiple times, so long as the total cumulative amount is below the limit. In fact, in some variations, the maximum amount the elongate member may advance without being retracted may be less than its total advancement amount. For example, the elongate member may advance about halfway around Schlemm's canal in a first direction a first time (i.e., 180 degrees, or about 19 mm to about 20 mm), which may be the maximum amount the elongate member may advance without being retracted. The elongate member may then be fully retracted (during which fluid may be delivered). After this first extension, the fluid assembly (2316) may have traveled half its maximum distance, and its distance to the linear gear (2204) may have decreased by about half of its total possible decrease. The delivery system (2300) may then be rotated about the handle, and the elongate member may advance about halfway around Schlemm's canal a second time in a second direction. The elongated member may then be retracted (during which fluid may be delivered). Upon completion of the second extension, the fluid assembly (2316) may be located at its distal-most position and its distance to the linear gear (2204) may be at its minimum. At this point, the elongated member may not advance any further, no additional fluid may be deliverable, and the wheel may not rotate any further.

[0119] Devices not configured to deliver fluids It should be understood that not all delivery systems described herein are configured to deliver a fluid composition. Devices not configured to deliver a fluid composition may operate similarly to delivery systems configured to deliver a fluid composition, but retraction or advancement of the elongate member may not result in simultaneous delivery of the fluid composition. In some examples, the delivery system may be identical to one configured to deliver a fluid composition, but may not be filled with a fluid composition. In other examples, the elongate member of a delivery system not configured to deliver a fluid composition need not include a lumen. Similarly, a delivery system not configured to deliver a fluid composition need not include a reservoir or plunger. Instead of a reservoir, the delivery system may include a solid surrogate component having a similar profile to the fluid assembly. The surrogate component may connect to the linear gear of the delivery system via a linkage that may or may not be integral with the surrogate component. This may simplify manufacturing, as many of the components may be interchangeable between delivery systems configured to deliver a fluid composition and delivery systems not configured to deliver a fluid composition. Thus, like delivery systems configured to deliver fluids, systems not configured to deliver fluids may or may not be configured to allow for a certain cumulative amount of extension and / or storage, as described in more detail herein.

[0120] Some delivery systems that are not configured to deliver a fluid composition may be configured such that the elongated member disrupts the trabecular meshwork. In some variations, the elongated member may be configured such that advancement and / or retraction of the elongated member may disrupt the trabecular meshwork, and the elongated member may include one or more features to facilitate disruption of the trabecular meshwork upon advancement or retraction, e.g., a disrupting component at the distal end of the elongated member, such as a barb, hook, balloon, or the like. In other variations, the elongated member may be configured such that the body of the elongated member is configured to cut or tear the trabecular meshwork. For example, the delivery system may be configured such that the elongated member is advanced out of the cannula and around Schlemm's canal, and if the cannula is subsequently removed from the eye without retracting the elongated member, the body of the elongated member may cut or tear the trabecular meshwork when the cannula is removed. The body of the elongate member may be configured to "unzip" the meshwork to cut or tear from a first location of the trabecular meshwork near the cannula tip (i.e., at the proximal end of the elongate member) and then around the trabecular meshwork toward the distal end of the elongate member. The elongate member may be configured to apply a shearing force to cut or tear the meshwork one meshwork location at a time and then around Schlemm's canal, rather than simultaneously cutting or tearing the mesh throughout the entire trabecular meshwork that is to be cut or tear with the shearing force.

[0121] Implantation of intraocular devices The cannula of the system described herein may also deliver various surgical instruments ab internally. For example, catheters, wires, probes, and other instruments may be used ab internally to access Schlemm's canal and then create holes, partial thickness disruptions, or perforations at discreet locations or along the entire inner wall of the trabecular meshwork or Schlemm's canal. The surgeon may also advance instruments across the entire canal and through the outer wall of the collector channel to access the sclera and subconjunctival space (again, all ab internally) to make incisions that create scleral lakes into which aqueous humor can drain and flow to the scleral veins or subconjunctival space, or ab internally deliver intraocular devices that reside in the scleral space or subconjunctival space and drain into it from the anterior chamber or Schlemm's canal.

[0122] When the delivery system is used to implant an intraocular device, the cannula may include a slidable positioning element disposed coaxially within the lumen of the cannula. The slidable positioning element generally includes an engagement mechanism for manipulation, e.g., releasable engagement, advancement, and / or retraction of the intraocular device. Exemplary engagement mechanisms are shown in Figures 5-9.

[0123] In Figure 5A, the engagement mechanism (500) comprises a first jaw (502) and a second jaw (504). In their closed configuration (shown in Figure 5A), the jaws (502, 504) are constrained within a cannula (512) to hold an intraocular device (506) comprising a support (508) and at least one fenestration (510). Once the jaws (502, 504) are advanced out of the cannula (512), the jaws are no longer constrained and therefore assume their open configuration, as shown in Figure 5B. Opening of the jaws (502, 504) releases the intraocular device (506) from the engagement mechanism (500). At least one tine (514) may be provided in the first jaw (502) and at least one aperture (516) may be provided in the second jaw (504) to aid in securing the fenestrated intraocular 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 second jaw (604) include both tines (606) and apertures (608) to aid in gripping the fenestrated intraocular device (610).

[0124] 7A-7B, further exemplary engagement mechanisms are shown. In FIG. 7A, the engagement mechanism (700) comprises a complementary mating element. Specifically, the engagement mechanism (700) includes a female element, a notch (702), which is configured to mate with a complementary male element (704), shown as a hook-like protrusion on the intraocular device (706). Here, the notch (702) may be manufactured at the end of a hypodermic tube (708) (which may act as a positioning element). Instead of a notch (702), the female element of the engagement mechanism (710) may have an opening (712), as shown in FIG. 7b, which mates with the male element (704) on the intraocular device (706). In FIG. 7B, the positioning element (714) may be manufactured from a metal wire or rod, and the opening (712) is created by laser machining or other processes known in the art.

[0125] In other variations, the engagement mechanism may be configured as shown in Figures 8A and 8B. In these figures, the engagement mechanism (800) comprises an annular portion (802). This particular engagement mechanism may be beneficial for use with an intraocular device (804) that includes a catch (806) with an arm or tab (808) having a closed configuration and an deployed configuration. Similar to the variation shown in Figures 5A and 5B, the tab (808) is constrained in a closed configuration within the cannula (810) prior to advancement from the cannula (810). In these constrained configurations, the tab (808) engages the annular portion (802) of the engagement mechanism (800) to prevent release of the intraocular device (804) from the system. When the annular portion (802) of the engagement mechanism (800) is advanced sufficiently that the tab (808) is no longer constrained by the cannula (810), the tab (808) assumes its deployed configuration, releasing the intraocular device (804) from the annular portion (802) into Schlemm's canal, as shown in FIG. 8B.

[0126] Another exemplary engagement mechanism (900) is shown in Figure 9, comprising a coiled portion (902) and a hook (904). When an intraocular device (906) having at least one fenestration (908) (e.g., a proximal fenestration) is implemented, the hook (904) may releasably engage the fenestration (908). The intraocular device (906) may be disengaged from the hook by application of a gentle force to the coil (902) or by another component (not shown) that can be advanced over the coil (902) to push the device (906) off the hook (904). It may be advantageous to use the hook (904) when storage of the intraocular device (906) is desired.

[0127] The intraocular delivery system may further include a slidable positioning element disposed coaxially within the lumen of the cannula for controlled deployment of the intraocular device in Schlemm's canal. The positioning element generally comprises a proximal end, a distal end, and an engagement mechanism at the distal end. The intraocular device generally releasably couples to the engagement mechanism. The positioning element may be advanced to deploy the intraocular device within the cannula into Schlemm's canal or may be retracted to aid in positioning and / or repositioning the intraocular device or disengagement of the intraocular device from the engagement mechanism.

[0128] Some variations of the engagement mechanism include a proximal coiled portion and a distal hook. If an implant having at least one fenestration (e.g., a proximal fenestration) is implemented, the hook may releasably engage the fenestration. The intraocular device may disengage from the hook by application of a gentle force to the coil, or by another component that can be advanced over the coil to push the device off the hook, or by using a shape memory material that passively disengages as it exits the cannula. It may be advantageous to use the hook when storage of the intraocular device is desired. The surgeon may simply move the delivery system and engagement mechanism so that they disengage from any fenestrations or notches on the implant.

[0129] In another variation, the engagement mechanism includes opposing jaws. Here, the engagement mechanism may include a first jaw and a second jaw, the jaws having a closed configuration and an open configuration. The jaws may be used to grasp and manipulate the intraocular device and to releasably couple the intraocular device to the positioning element. The jaws may be formed by splitting or bifurcating the distal end of a wire, for example by laser cutting. The gripping force of the jaws may be obtained by constraining the jaws within the cannula. The intraocular device may be released as the jaws advance out of the cannula and deploy. The jaws may also be pivotally connected. In yet another variation, the first jaw may include at least one tine and the second jaw may include at least one aperture for receiving the tine when the jaws are in the closed configuration.

[0130] In a further variation, the engagement mechanism comprises an annular portion. This variation of the engagement mechanism will typically be used with an intraocular device that comprises a spring-like catch at its proximal end having a folded configuration and an expanded configuration. The catch is generally manufactured in a deployed position. Thus, when a device having the catch is disposed within a cannula, the first and second arms or tabs of the catch are folded around the annular portion of the engagement mechanism. When the clasped portion of the device exits the cannula, the arms or tabs may unfold to release the intraocular device from the annular portion.

[0131] Another variation of the engagement feature includes a female-male interface. For example, the engagement feature may comprise a notch configured to mate with a complementary mating element (e.g., a tab) on the intraocular device. The notch (female component) may be formed in the hypodermic tube or may be created by creating a fenestration through the distal end of the positioning element made from a solid wire or element, and the tab or hook (male component) may be formed as part of the intraocular device and inserted into the fenestration or notch in the positioning element. This configuration allows the intraocular device to be released from the positioning element as it advances from the cannula, either by the surgeon's manipulation or by a shape setting of the positioning element that passively disengages it from the intraocular device, or both.

[0132] II. Kit The delivery system described herein may be placed in a specialized package. The package may be designed to protect the system, and in particular to protect the cannula. It may be desirable for the package to prevent contact between the distal tip of the cannula and any other object or surface. To do so, the package may include one or more elements configured to secure the delivery system to the packaging at one or more locations proximal to the distal tip of the cannula. It may be desirable to secure the delivery system at at least two locations proximal to the distal tip of the cannula to limit the ability of the delivery system to pivot relative to the packaging.

[0133] In one exemplary variation, the packaging may include a tray with a recess having a shape generally corresponding to the shape of the delivery system and one or more corresponding pinch points configured to secure the delivery system at a location proximal to the cannula. FIG. 26A shows an exemplary tray (2604) for a delivery system (2600). The tray (2604) may include a recess (2606) configured to receive the delivery system (2600). The tray (2604) may include a first distal pinch point (2608) and a second distal pinch point (2610), and a first proximal pinch point (2612) and a second proximal pinch point (2614) configured to secure the delivery system (2600) within the recess (2606). When the delivery system (2600) is secured in the tray (2604), the cannula (2602) of the delivery system may be suspended so that the cannula does not contact the tray, and the pinch points may limit the delivery system (2600) from pivoting in such a way that the cannula (2602) may come into contact with the tray. The pinch points may be configured to securely secure the delivery system (2600) in the tray (2604) while also allowing the user to remove the delivery system from the tray in a controlled manner. In variations in which the kits described herein include additional components, the packaging may be designed to hold these additional components. For example, FIG. 26B shows an exemplary tray (2626) with a recess (2628) configured to hold the filling device (2624) and the delivery system (2620). As shown in FIG. 26C, the tray (2640) may be configured to be sealed (e.g., heat sealed) by a lid (2642) and placed into a box (2644). Box 2644 may optionally further contain instructions for use 2646. Optionally, a label 2648 may be affixed to lid 2642 and / or box 2644.

[0134] It should be understood that the packaging may have other configurations that protect the distal tip of the cannula. For example, in another variation, the packaging may comprise a rigid planar sheet to which the delivery system may be attached in an orientation such that the cannula does not contact the planar sheet. The delivery system may be attached at two or more points along the housing to prevent movement of the delivery system relative to the planar sheet (e.g., by a string or other material wrapped around the housing). It may be desirable to protect the cannula on at least two sides. For example, a portion of the planar sheet proximate to the cannula may be bent around the cannula to protect the cannula on at least two sides, or a second rigid planar sheet may be attached to the delivery system on the opposite side of the first planar sheet.

[0135] Some kits described herein may include multiple delivery systems. For example, the kit may include two delivery systems. In some variations, the kit may include two of the same systems, such that, for example, a first delivery system may be used in a first eye of a patient and a second delivery system may be used in a second eye of a patient. In other variations, the 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 instead be configured to disrupt the trabecular meshwork using an elongate member. Kits including multiple systems may be packaged in any suitable manner. For example, FIG. 27A illustrates a kit including two delivery systems (2700, 2702) in a stacked configuration (shown without outer packaging) and FIG. 27B illustrates a kit including two delivery systems (2704, 2706) in a side-by-side configuration (shown without outer packaging). Again, the delivery systems (2700, 2702) may both be configured to deliver a fluid composition, both may be configured not to deliver a fluid composition (e.g., configured to deliver an elongate member to disrupt the trabecular meshwork), or one may be configured to deliver a fluid composition and the other not. Similarly, the delivery systems (2704, 2706) may both be configured to deliver a fluid composition, both may be configured not to deliver a fluid composition, or one may be configured to deliver a fluid composition and the other not.

[0136] Some kits may include an intraocular implant in addition to one or more delivery systems described herein. For example, the kit may include one or more devices configured to be implanted in Schlemm's canal, which may be configured to generally maintain the patency of Schlemm's canal without significantly interfering with transmural fluid flow across the canal. The kit may include one or more intraocular implants, such as, but not limited to, a stent for placement in Schlemm's canal. In some variations, the intraocular implant may be one or more of those disclosed in U.S. Pat. No. 7,909,789, which has already been incorporated by reference in its entirety, and U.S. Pat. No. 8,529,622, which has already been incorporated by reference in its entirety. In one variation, the device may include a twisted ribbon member, which includes a double helix including a first elongated edge, 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 ribbon member. The struts may define a plurality of fenestrations spaced along at least a portion of the length of the twisted ribbon member.

[0137] III. Method Methods for treating ocular conditions and / or implanting intraocular devices and using the above-described systems to deliver fluid compositions and / or instruments to Schlemm's canal are also provided. In some examples, treating ocular conditions may lead to increased aqueous drainage, reduced resistance to aqueous outflow, and / or reduced intraocular pressure. Some methods described herein may dilate Schlemm's canal, dilate collector channels, and / or disrupt any septa that may obstruct circumferential flow through Schlemm's canal. Dilation of Schlemm's canal may disrupt the obstructed inner wall of the canal, tension the trabecular meshwork, and / or increase the porosity of the trabecular meshwork. This improves the natural aqueous outflow pathway. Dilation may be performed by advancing an instrument (e.g., a slidable elongate member described herein). Additionally or alternatively, dilation may be performed by delivering a fluid composition (e.g., a viscoelastic fluid described herein). Additionally or alternatively, some methods described herein may include performing a trabeculotomy to cut the trabecular meshwork. Additionally or alternatively, some methods described herein may include implanting an intraocular device into Schlemm's canal. In some examples, the systems described herein may be used to perform abinterno trabeculotomy, abinterno transluminal trabeculotomy, clear corneal trabeculotomy, clear corneal transluminal trabeculotomy, abinterno tuberculoplasty, and / or clear tuberculoplasty. The delivery system may also be used in some examples to dissolve anterior chamber adhesions, perform viscoelastic viscogonioplasty, assist with intraocular lens exchange, float a dropped lens or foreign body, and / or reposition herniated iris tissue.

[0138] The methods are generally minimally invasive, single-operator, single-handed controlled methods, for example, adapted to ab interno procedures, which may be advantageous over more invasive ab externo procedures as described above. However, the use of intraocular systems in ab externo procedures is contemplated in some instances and is not excluded herein. An intraocular device or method for delivering fluids or for providing a disruptive force may be used to treat or prevent glaucoma, pre-stage glaucoma, or ocular hypertension. When treating glaucoma, the methods may also be used in combination with (before or after) cataract surgery, using the same incision during the same session, or at another time.

[0139] Some of the methods, described in more detail below, may include dilating (e.g., with a viscoelastic fluid) Schlemm's canal and / or aqueous humor collector channels using the delivery systems described herein. Other of the methods, also described in more detail below, may include tearing or cutting the trabecular meshwork of Schlemm's canal. These methods may be performed separately or combined into a single procedure. For example, in some instances, a portion (e.g., half) of Schlemm's canal may be dilated (e.g., using a fluid composition or an instrument, or both) and the trabecular meshwork of the same or a different portion of Schlemm's canal may be teared or cut in the same eye. As another example, all of Schlemm's canal may be dilated, and then all or a portion of the trabecular meshwork may be subsequently teared or cut. This may be desirable, for example, to both dilate the collector channels and tear or cut the trabecular meshwork.

[0140] In some of these variations, the expanding and tearing or cutting can be performed using a single delivery system, such as one described herein, that is configured to deliver a fluid composition. For example, the elongated member of the delivery system configured to deliver the fluid composition can be used first to deliver the fluid composition to a portion of Schlemm's canal (e.g., about a 180-degree arc of the canal, about a 90-degree arc of the canal), as described herein, and then tear or cut the trabecular meshwork in the same portion of the canal, as described herein. As another example, the elongated member of the delivery system configured to deliver the fluid composition can be used first to deliver the fluid composition to a portion of Schlemm's canal (e.g., about a 180-degree arc of the canal, about a 90-degree arc of the canal, etc.), and then tear or cut the trabecular meshwork in a different portion of the canal (e.g., one about a 180-degree arc, another about a 90-degree arc, etc.). As yet another example, an elongate member of a delivery system configured to deliver the fluid composition may first be used to deliver the fluid composition to all of Schlemm's canal (e.g., by delivering approximately 180 degrees of the fluid composition in a first direction and then delivering approximately 180 degrees of the fluid composition in a second direction), and then subsequently tear or cut the entire 360 ​​degrees of the trabecular meshwork (e.g., by tearing or cutting approximately 180 degrees of the trabecular meshwork in a first direction and then tearing or cutting approximately 180 degrees of the trabecular meshwork in a second direction).

[0141] In other variations, the dilating and tearing or cutting may be performed using different delivery systems (e.g., the dilating may be performed using a delivery system configured to deliver a fluid composition and the tearing or cutting may be performed using a delivery system not configured to deliver a fluid).As yet another example, in some cases, dilating may be performed in one eye of a patient while simultaneously tearing or cutting the trabecular meshwork in the other eye of the patient.

[0142] The means for dilating Schlemm's canal and / or tearing or cutting the trabecular meshwork may be combined with a procedure for delivering an intraocular device (described in more detail herein) to the same eye or to a different eye of the same patient. For example, all or a portion of Schlemm's canal may be dilated before an intraocular device is inserted. As another example, a portion of the trabecular meshwork may be teared or cut and an intraocular implant may be delivered to another portion of Schlemm's canal at the same time. As yet another example, a portion of Schlemm's canal may be dilated and an intraocular implant may be delivered to another portion of Schlemm's canal at the same time. As yet another example, an intraocular implant may be delivered to a portion of Schlemm's canal, which may then be subsequently dilated to improve the function of the intraocular implant.

[0143] Intraocular Device Delivery Generally, a method for implanting an intraocular device into Schlemm's canal includes first creating an incision in the eye wall (e.g., the sclera or cornea or corneoscleral limbus or junction) that provides access to the anterior chamber of the eye. As shown in the stylized depiction of the eye in FIG. 14, a cannula (1400) of an intraocular delivery system is then advanced through the incision, across at least a portion of the anterior chamber (1402), and into the trabecular meshwork (not shown). Schlemm's canal (i.e., the lumen of Schlemm's canal) (1404) is then accessed by a distal curved portion (1406) of the cannula and a slidable positioning element (or, for example, a slidable instrument or guidewire), or an elongated member (generally represented by element 1408) is advanced from the cannula to implant an intraocular device into Schlemm's canal, perform a procedure either in Schlemm's canal or the nearby trabecular tubule tissue, or deliver fluids to the canal. However, in some instances, an elongate member may not be used, such that any fluid delivered is delivered through the cannula, and in a further variation, the fluid composition is delivered by piercing only the trabecular meshwork without circumnavigating Schlemm's canal.

[0144] As previously mentioned, in some variations, the cannula may be configured to include a proximal end and a distal curved portion, the distal curved portion having a proximal end, 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, e.g., adjacent, the radius of curvature. In other variations, a straight cannula (i.e., one that does not have a distal curved portion) may be used to access Schlemm's canal. The method may also include flushing the system with fluid (e.g., to remove air from the system) and / or irrigating the surgical field to clear blood or improve visualization of the surgical field.

[0145] Any suitable intraocular device that maintains the patency of Schlemm's canal or improves the outflow of aqueous humor may be implanted by the system described herein. For example, an intraocular device that maintains the patency of Schlemm's canal without significantly interfering with fluid flow across, along, or out of the canal may be implanted. Such a device may comprise a support having at least one fenestration, as disclosed in U.S. Patent No. 7,909,789 and U.S. Patent No. 8,529,622, which have already been incorporated by reference in their entirety. An intraocular device that disrupts the proximal trabecular meshwork or the inner wall of the adjacent Schlemm's canal may also be implanted. In addition to intraocular devices made of metals or metal alloys, sutures, modified sutures, modified polymers, polymer filaments, or solid viscoelastic structures may be delivered. Fluid compositions, such as saline, viscoelastic fluids, air, drug mixtures or solutions, and gases may also be delivered.

[0146] When delivering the fluid composition to Schlemm's canal, the method generally includes the steps of creating an incision in the eye wall (e.g., sclera or cornea) that provides access to the anterior chamber of the eye, advancing a cannula of an intraocular delivery system through the incision and at least partially across the anterior chamber to the trabecular meshwork, accessing Schlemm's canal with the cannula, and delivering the fluid composition to the canal using an elongate member that is slidable within the lumen of the cannula. The cannula may be configured to include a proximal end and a distal curved portion, the distal curved portion having 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, e.g., adjacent to, the radius of curvature. Further advantageous cannula features may be included, which have been described above. The method may also include the steps of flushing the system with a fluid (e.g., to remove air from the system) and / or irrigating the surgical field to clear blood or improve visualization of the surgical field.

[0147] When using the abinterno technique to implant an intraocular device, the method may include the following steps: The surgeon may first use an operating microscope and a gonioscope or gonioprism to view the anterior chamber and trabecular meshwork (underlying Schlemm's canal). Next, using a corneal, limbal, or scleral incision of 0.5 mm or more, the surgeon may gain access to the anterior chamber. Next, a saline solution or a viscoelastic composition may be introduced into the anterior chamber to prevent it from collapsing. Here, the saline solution or the viscoelastic composition may be delivered through a delivery system cannula or in another manner, for example, by injection through an irrigation sleeve on the cannula. The surgeon then advances the delivery system cannula through the incision toward the anterior chamber angle under direct microscopic visualization. Once the angle (and therefore the trabecular meshwork) is close, the surgeon may apply a gonioscope or gonioprism to the cornea to visualize the angle. Application of a fluid (e.g., a viscous solution or viscoelastic composition as previously described) to the cornea and / or application of a gonioscopic or gonioprism may allow visualization of the anterior chamber angle by achieving good optical contact and eliminating total internal reflection. Once the surgeon has visualized the trabecular meshwork, the cannula may then be advanced so that the bevel at the distal end of the curved distal portion of the cannula pierces the meshwork and communicates with the lumen of Schlemm's canal. The surgeon may irrigate the canal or anterior chamber with saline or a viscoelastic composition to prevent the anterior chamber from collapsing, to dilate Schlemm's canal, or to flush out any blood that may impede cannula visualization and intraocular device delivery. Then, once the intraocular device has been advanced to the extent desired by the surgeon, the device may be released from the engagement mechanism so that it resides in Schlemm's canal. If repositioning of the intraocular device is required or desired, the surgeon may use the positioning element of the delivery system to store and / or reposition the intraocular device. The surgeon may then withdraw the delivery system from the eye.

[0148] Other variations of the abinterno technique for implanting intraocular devices include the use of an endoscope. As with the above method, the anterior chamber is first accessed by making an incision in the cornea, limbus, or sclera. Again, this may be done once before or after cataract surgery in conjunction with cataract surgery, or may be done independently. The anterior chamber may be infused with saline solution, or a viscoelastic composition may be placed in the anterior chamber to prevent it from collapsing. The saline or viscoelastic may be delivered as a separate step, or may be injected using an elongate member of the delivery system, an irrigation sleeve on the elongate member or cannula, or a separate injection cannula. The surgeon then advances the endoscope through the incision toward the angle and trabecular meshwork under direct microscopic visualization. Once the surgeon has visualized the trabecular meshwork using the endoscope or any associated video display, the bevel of the cannula advances to puncture the meshwork. The intraocular device is then advanced using a positioning element under endoscopic visualization. The surgeon may irrigate the canal or anterior chamber with saline or a viscoelastic composition to prevent the anterior chamber from collapsing, to dilate Schlemm's canal, or to flush out any blood that may impede cannula visualization and intraocular device delivery. Once the intraocular device has been advanced as far as the surgeon desires, the device may be released from the engagement mechanism so that it resides in Schlemm's canal. If repositioning of the intraocular device is needed or desired, the surgeon may use the positioning elements of the delivery system to retract and / or advance the intraocular device. The surgeon may then withdraw the delivery system from the eye.

[0149] fluid composition delivery Some methods described herein may include delivering a fluid composition into an eye, such as into Schlemm's canal. In some methods, an elongated member with a lumen may be advanced into Schlemm's canal, and the fluid composition may be delivered through the elongated member. Delivery of both the elongated member and the fluid may dilate Schlemm's canal, and fluid delivery may further dilate the collector channel. For delivery of the fluid composition, the method is similar to implantation of an intraocular device. However, instead of using a positioning element, the delivery system may use a slidable elongated member to inject the fluid composition into Schlemm's canal.

[0150] The fluid composition may be delivered to dilate Schlemm's canal. The entire length of Schlemm's canal or a portion thereof may be dilated by the fluid. For example, at least 75%, at least 50%, at least 25%, at least 10%, or at least 1% of the canal may be dilated. The fluid composition may also be delivered to treat various medical conditions of the eye, including, but not limited to, glaucoma, pre-stage glaucoma, anterior or posterior neovascular disease, anterior or posterior inflammatory disease, ocular hypertension, uveitis, age-related macular degeneration, diabetic retinopathy, genetic eye disorders, complications of cataract surgery, vascular occlusion, vascular disease, or inflammatory disease.

[0151] The surgeon may first use an operating microscope and a gonioscope or gonioprism to view the anterior chamber and trabecular meshwork (underlying Schlemm's canal). Next, using a corneal, limbal, or scleral incision of 0.5 mm or more, the surgeon may gain access to the anterior chamber. A saline solution or viscoelastic composition may then be introduced into the anterior chamber to prevent it from collapsing. Here, the saline solution or viscoelastic composition may be delivered through a delivery system cannula or in another manner, for example, by injection through an irrigation sleeve on the cannula. The surgeon then advances the delivery system cannula through the incision toward the anterior chamber angle under direct microscopic visualization. Once the angle (and therefore the trabecular meshwork) is close, the surgeon may apply a gonioscope or gonioprism to the cornea to visualize the angle. Application of various fluids (e.g., viscoelastic compositions as previously described) to the cornea and / or application of a gonioscope or gonioprism may allow visualization of the anterior chamber angle by achieving good optical contact and eliminating total internal reflection. Once the surgeon has visualized the trabecular meshwork, the cannula may then be advanced such that the bevel at the distal end of the curved distal portion of the cannula pierces the meshwork and communicates with the lumen of Schlemm's canal.

[0152] A slidable elongate member disposed coaxially within the lumen of the cannula may then be advanced into the canal under gonioscopic visualization. The elongate member may be advanced any suitable amount and direction around the canal. For example, the elongate member may be advanced about 1 degree to about 360 degrees around the canal, about 10 degrees to about 360 degrees around the canal, about 150 degrees to about 210 degrees around the canal, or any suitable distance, about 360 degrees around the canal, about 270 degrees around the canal, about 180 degrees around the canal, about 120 degrees around the canal, about 90 degrees around the canal, about 60 degrees around the canal, about 30 degrees around the canal, or about 5 degrees around the canal. In some variations, the elongate member may be advanced in two steps, for example, first clockwise (e.g., about 180 degrees, about 90 degrees, etc.) and then counterclockwise (e.g., about 180 degrees, about 90 degrees, etc.) around the canal (e.g., thereby achieving a 360 or 180 degree abinternoviscocanalostomy or canaloplasty). Fluid may be injected upon advancement or retraction of the elongate member. Once the slidable elongate member is positioned within the canal, a fluid composition, for example, a viscoelastic solution, may be delivered continuously or intermittently through the lumen of the elongate member. The fluid composition exits the lumen of the elongate member through its distal end (e.g., through the distal tip), or through openings or fenestrations provided along its shaft, or a combination of both. The openings or fenestrations may be spaced in any suitable manner along the axial length of the elongate member, for example, symmetrically or asymmetrically along its length. If desired, other substances, such as drugs, air, or gases, may be delivered in the same manner.

[0153] In some variations, the slidable elongate member may be repositioned by retraction or repeated advancement and retraction. In some variations of the method, the same or different incisions may be used, but a delivery system cannula is used to access and dilate Schlemm's canal from a different direction (e.g., counterclockwise instead of clockwise). Once a sufficient amount of fluid has been delivered, the surgeon may retract the slidable elongate member into the cannula and remove the delivery system from the eye. It is understood that the cannulas described herein may be specifically manufactured with a bi-surface configuration (i.e., a sharp side and a smooth side) at the distal tip, which may allow the elongate member to be advanced, repositioned, and / or retracted without breaking it off on the distal tip of the cannula. It is also understood that these steps may be used alone or in combination with cataract surgery (at once).

[0154] Some of the delivery systems described herein may be configured to limit the cumulative amount of advancement and / or retraction of the slidable elongate member. For example, as described above, after the elongate member has been advanced and retracted a certain cumulative distance (e.g., about 39 mm to about 40 mm, each advancement and retraction, corresponding to approximately the circumference of Schlemm's canal; or about 78 mm to about 80 mm, each advancement and retraction, corresponding to approximately twice the circumference of Schlemm's canal; or any other suitable distance), it cannot be advanced any further. This advancement and retraction may occur over multiple advance-retract cycles. For example, the elongate member may be advanced about 20 mm, then retracted about 20 mm, then advanced about 20 mm, then retracted about 20 mm. If the cumulative distance is limited to about 40 mm, after these two cycles of advancement and retraction, the elongate member may not be advanced any further.

[0155] In some variations of the Abinterno method, the fluid composition may be delivered simultaneously with retraction of the elongated member (i.e., the fluid composition may be delivered in a manner that allows the retraction of the system components to advance the fluid from the cannula of the system). Referring again to FIGS. 11A-11C, the linear gear (1108) is retracted in the direction of the arrow (FIG. 11B) such that the reservoir (1102) is pressurized. Retraction may be accomplished by rotation of the pinion gear mechanism (1120). Once a sufficient amount of pressure is created in the reservoir (1102), the fluid composition contained therein is injected through the linear gear lumen (1114) and the elongated member (1118) into Schlemm's canal. It should be understood that the intraocular delivery system may be configured such that the fluid composition is delivered continuously, passively, automatically, or actively by the surgeon. The fluid composition may also be delivered to the canal by a pump or auxiliary plunger independent of the movement of the gear shaft. In some variations, retraction of the elongate member may correspond to a volume of the fluid composition being delivered through the lumen of the elongate member. The fluid composition may be delivered through a distal opening of the lumen of the elongate member as it is retracted, such that the fluid may be delivered uniformly throughout the portion of the canal through which the elongate member is advanced.

[0156] The fluid compositions that may be delivered by the intraocular devices described herein include, but are not limited to, saline and viscoelastic fluids. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, derivatives 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 include 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 include an agent that aids in visualization of the viscoelastic composition. For example, a dye may be included, such as, but not limited to, fluorescein, trypan blue, or indocyanine green. In some variations, a fluorescent or bioluminescent compound is included in the viscoelastic composition to aid in its visualization. In other variations, the system delivers only the drug without the viscoelastic composition. In this case, the drug may be loaded onto or into a sustained release biodegradable polymer that elutes the agent over weeks, months, or years. It is also contemplated that air or gas may be delivered using the present system as described herein.

[0157] Other variations of the abinterno technique for delivering the fluid composition include the use of an endoscope. As with the method described immediately above, the anterior chamber is first accessed by making an incision in the cornea, limbus, or sclera. Again, this may be done once before or after cataract surgery in conjunction with cataract surgery, or may be done independently. The anterior chamber may be infused with saline solution, or a viscoelastic composition may be placed in the anterior chamber to prevent it from collapsing. The saline or viscoelastic may be delivered as a separate step, or may be injected using an elongated member of the delivery system, an irrigation sleeve on the elongated member or cannula, or a separate injection cannula. The surgeon then advances the endoscope through the incision toward the angle and trabecular meshwork under direct microscopic visualization. Once the surgeon visualizes the trabecular meshwork with the endoscope or any associated view, the bevel of the cannula advances to puncture the meshwork. The elongated member is then advanced under endoscopic visualization. The elongated member may be advanced any suitable amount and direction around the canal. For example, the elongate member may be advanced from about 10 degrees to about 360 degrees around the canal, or may be advanced in two steps, for example, 180 degrees clockwise and 180 degrees counterclockwise around the canal (thereby achieving a full 360 degree abinternoviscocanalostomy). Once the elongate member is positioned within the canal, a fluid composition, for example, a viscoelastic fluid, may be delivered continuously or intermittently through the lumen of the elongate member. The fluid composition exits the lumen of the elongate member through its distal end (e.g., through the distal tip), or through openings or fenestrations provided along its shaft, or a combination of both. The openings or fenestrations may be spaced along the axial length of the elongate member in any suitable manner, for example, symmetrically or asymmetrically along its length. If desired, other substances, such as drugs, air, or gases, may be delivered in the same manner. The elongate member may be retracted or repositioned by repeated advancement and retraction. In some variations of the method, the same or a different incision may be used, but a delivery system cannula is used to access and dilate Schlemm's canal from a different direction (e.g., counterclockwise instead of clockwise).Once a sufficient amount of fluid has been delivered, the surgeon may retract the slidable elongate member into the cannula and remove the delivery system from the eye.

[0158] One variation described herein is illustrated in Figures 28A-D, which may be performed using the delivery system described with respect to Figures 23A-23F. Figure 28A shows a flow diagram illustrating the method. The method shown therein may allow for one-handed manual delivery of fluid (e.g., viscoelastic fluid or gel) to Schlemm's canal via a slidable elongate member (e.g., a microcatheter) with a lumen. The delivery of the viscoelastic fluid may be metered so that small, controlled amounts of viscoelastic may be delivered to the eye. The method may allow for 360 degree catheterization and transluminal viscoelastic viscodilation of Schlemm's canal using a single clear corneal incision for access. This may reduce intraocular pressure, for example, in patients suffering from glaucoma (e.g., open-angle glaucoma).

[0159] First, the delivery system may be removed from its packaging. The delivery system may then be filled with viscoelastic fluid. A filling tool (e.g., a nozzle), which may be supplied with the delivery system in a kit, may be attached to the viscoelastic cartridge. Suitable commercially available viscoelastic materials include, but are not limited to, Healon™, HealonGV™, Amvisc™, and PROVISC™. The filling tool may then be filled with viscoelastic material. The lock on the proximal end of the delivery system may then be rotated (while still attached to the handle of the device) to expose a proximal opening in the device. The nozzle may then be inserted into the proximal opening and the viscoelastic fluid may be injected from the viscoelastic cartridge into the reservoir of the delivery system. It may be desirable to hold the delivery system and viscoelastic cartridge upright during injection. The viscoelastic fluid may be injected until a flow of viscoelastic material is visible from the distal tip of the cannula. The lock is then removed from the delivery system.

[0160] To deliver the viscoelastic fluid into the eye, the cannula may be advanced through an existing corneal or scleral incision into the anterior chamber. It may be desirable for the incision to be at least about 1 mm wide. The distal tip of the cannula may be used to puncture the trabecular meshwork and enter Schlemm's canal. The cannula may be held stationary relative to the angle while the elongated member is advanced into Schlemm's canal. An exposed portion of one or more of the wheels of the drive assembly may be rotated proximally such that the elongated member advances around Schlemm's canal up to about 180 degrees (about 18 mm, about 19 mm, about 20 mm, about 18 mm to about 20 mm, or about 15 mm to about 25 mm of circumferential canal movement). At this point, the elongated member may be fully extended and the wheels may not be able to rotate any further. Visualization of the cannula tip may be maintained during this procedure by direct microscopy or gonioscopically, and the anterior chamber may be maintained by viscoelastic or continuous balanced salt solution infusion.

[0161] The one or more wheels may then be rotated distally to retract the elongate member. As the elongate member is retracted, a specific, predetermined volume of viscoelastic material may be continuously delivered from the lumen of the elongate member in a metered manner, which may cause dilation of Schlemm's canal and / or collector channel with the viscoelastic material. In some variations, full retraction of the elongate member results in the delivery of about 2 μl to about 9 μl of viscoelastic fluid (e.g., about 4.5 μl of viscoelastic fluid). The wheels may be configured to rotate incrementally with an audible and / or tactile click upon incremental rotation, and in some cases, about 0.5 μl of viscoelastic fluid may be delivered with each click. The delivery of viscoelastic material (2800) to Schlemm's canal (2802) and collector channel (2804) during retraction of the elongate member (2806) into the cannula (2808) is shown in FIGS. 28B-28D. As seen in Figures 28C-28D, the angle and length of delivery of the viscoelastic material (2800) into Schlemm's canal corresponds to the angle and length of advancement of the elongate member into the canal. In some instances, the viscoelastic material may be used to tamponade any reflux of blood back into the anterior chamber.

[0162] Optionally, the viscoelastic material may then be delivered to the other half of Schlemm's canal. The cannula tip may be removed from Schlemm's canal and the delivery system may be inverted so that the cannula tip rotates 180 degrees to face the opposite direction. In some instances, the delivery system may be inverted in the anterior chamber without removing the cannula from the eye. In other instances, the delivery system may be removed from the eye, inverted, and reinserted into the incision. The cannula tip may then be reinserted into Schlemm's canal through the same incision in the trabecular meshwork, and the above advancement, retraction, and delivery of viscoelastic fluid may be repeated to dilate the remaining 180 degrees of Schlemm's canal with the viscoelastic material. Upon completion of the procedure, a total of about 4 μl to about 18 μl of viscoelastic fluid (e.g., about 9 μl of viscoelastic fluid) may be delivered to the eye.

[0163] At the end of the procedure, the anterior chamber may be irrigated (e.g., with balanced salt solution) through the corneal wound (manually or automatically). Balanced salt solution or viscoelastic substances may be used to reshape the anterior chamber as needed to achieve physiological pressure and to further tamponade any backflow of blood from the collector channel back into the anterior chamber. If necessary, sutures may be used to seal the corneal or scleral incisions. Postoperatively, antibiotics or antiseptics, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for several weeks or months to help prevent adhesion formation and angle closure.

[0164] More generally, exemplary volumes of viscoelastic fluid that may be delivered in the methods described herein may range from about 1 μl to about 200 μl, or in some examples, from about 1 μl to about 100 μl. In some examples, volumes sufficient to provide a disruption 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 disrupt Schlemm's canal and / or surrounding tissue. In other variations, the volume of viscoelastic material sufficient to disrupt 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.

[0165] Tissue disruption may occur by excessive and deliberate viscoelastic expansion with at least about 1 μl, at least about 2 μl, at least about 3 μl, at least about 4 μl, at least about 5 μl, at least about 6 μl, at least about 7 μl, at least about 8 μl, at least about 9 μl, at least about 10 μl, at least about 11 μl, at least about 12 μl, at least about 13 μl, at least about 14 μl, at least about 15 μl, at least about 16 μl, at least about 17 μl, at least about 18 μl, at least about 19 μl, or at least about 20 μl of viscoelastic fluid per 360 degree arc of the canal. In some variations, at least about 20 μl, at least about 25 μl, at least about 30 μl, at least about 35 μl, at least about 40 μl, at least about 45 μl, or at least about 50 μl of viscoelastic fluid may be delivered.

[0166] Depending on factors such as the type and severity of the condition being treated, the disruption force may be generated to partially or completely disrupt and / or remove the trabecular meshwork and may be adjusted by varying the volume of viscoelastic fluid delivered. For example, 8 μl may be used to perforate or gently tear the meshwork, while 16 μl may be used to maximally cut or tear the meshwork. More specifically, about 1-2 μl may be used to dilate Schlemm's canal and collector channels, about 2-4 μl may be used to dilate Schlemm's canal and collector channels and stretch the adjacent tubular tissue, and about 4-6 μl may be used to do all of the above as well as create micro-tears or micro-perforations in the trabecular meshwork and adjacent tubular tissue (thereby further increasing porosity and outflow). A volume of about 8-16 μl may be used to do all of the above and significantly perforate / tear the trabecular meshwork and adjacent tubular tissue. A volume of about 16-50 μl may be used to significantly or completely tear or cut the trabecular meshwork.

[0167] The entire volume of viscoelastic fluid may be delivered along a 360 degree arc (1600) of Schlemm's canal during a single advancement (e.g., as shown in FIG. 16) or withdrawal of the elongate member (1604) from a single access point (1602) in the canal, or along a lesser number of arcs in multiple advancements or withdrawals of the elongate member. For example, as shown in FIG. 17, the elongate member (1700) may be advanced along a 180 degree arc of the canal in both a clockwise (1702) and counterclockwise (1704) direction to deliver fluid, for example, from a single access point (1706) in the canal. 16 and 17, an exemplary cutoff volume of about 4 μl to about 18 μl may be delivered along a 360-degree arc of the canal while the elongate member is advanced from a single access point in the canal, or about 2 μl to about 9 μl may be delivered along a 180-degree arc of the canal during two advancements (one clockwise and one counterclockwise) of the elongate member from a single access point in the canal. More specifically, an exemplary cutoff volume may be about 9 μl delivered along a 360-degree arc of the canal, or about 4.5 μl delivered along a 180-degree arc of the canal during each of two advancements. The elongate member may access the canal from a single point or from multiple points.

[0168] In addition, the fluid composition may be delivered to restore the canal structure of Schlemm's canal, clear blockages in the canal, disrupt the proximal trabecular meshwork in the canal or the inner wall of Schlemm's canal, or enlarge the canal. Here, the delivery system may include wires, tubes, balloons, devices that deliver energy to tissue, and / or other features to aid in these methods. It is contemplated that such systems with additional features may be used to treat glaucoma. The surfaces of these systems may be roughened or have protrusions to further disrupt the inner wall of Schlemm's canal and the proximal trabecular meshwork to enhance aqueous humor outflow or permeability.

[0169] The viscoelastic fluid may be delivered while a single operator advances the elongated member of the single-handed device from Schlemm's canal in a clockwise, counterclockwise, or both directions and / or while the elongated member is withdrawn from Schlemm's canal. As described above, the viscoelastic fluid may be delivered to disrupt Schlemm's canal and the surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid may cause disruption by dilating Schlemm's canal, increasing the porosity of the trabecular meshwork, tensioning the trabecular meshwork, forming microscopic tears or perforations in the nearby tubule tissue, removing septa from Schlemm's canal, dilating the collector channel, or a combination thereof. The viscoelastic fluid may be loaded into the elongated member at the start of an ophthalmic procedure so that the fluid may be delivered by a single device. This is in contrast to other systems that use forceps or other advancement instruments for advancing the fluid delivery catheter into Schlemm's canal and / or devices containing a viscoelastic fluid that are separate or independent from the delivery catheter or catheter advancement instrument and must be tethered to the delivery catheter or catheter advancement instrument by an assistant while the delivery catheter or catheter advancement instrument is held by the surgeon during the procedure.

[0170] instrument delivery Prior to the introduction of goniotomy and trabeculotomy (both typically used at an early age to treat a blocked trabecular meshwork, often hereditary), congenital glaucoma uniformly led to blindness. Despite the invasiveness of goniotomy (performed ab interno, using a sharp scalpel to cut the meshwork 30-60 degrees to improve outflow) and trabeculotomy (ab externo technique, in which a deep scleral incision is made to unroof Schlemm's canal and a probe cuts the meshwork), the procedures have been considered effective and have allowed many pediatric patients to potentially avoid lifelong blindness. In 1960, Burian and Smith independently described ab externo trabeculotomy. In this highly invasive abexternal surgery, the surgeon makes a deep scleral incision, locates Schlemm's canal, externally cannulate the entire 360 ​​degrees of Schlemm's canal with a catheter or a specially designed probe called a trabectome, and finally pulls both ends of the catheter or probe until the trabectome cuts through the entire trabecular meshwork into the anterior chamber to improve drainage.

[0171] A more recent attempt to reduce the invasiveness of trabeculotomy has been developed by NeoMedix, which is commercializing a device called the "Trabectome." The Trabectome attempts to make trabeculotomy easier through the use of an abinterno technique. The device and method involves removing the trabecular meshwork abinterno with electrocautery using an instrument that also provides injection and suction. The disadvantages of the Trabectome are threefold: 1) the device uses an energy-based mechanism to remove the trabecular meshwork, which is believed to cause inflammation and scarring in the eye, which may adversely affect outflow and pressure as well; 2) the device / procedure is ergonomically limited as it requires a foot pedal and power cord to activate the electrocautery and irrigation, plus is limited to treating 60-120 degrees of meshwork per corneal or scleral entry incision; and 3) capital equipment is required as it involves energy-based removal and irrigation.

[0172] The methods (and systems and devices) described herein, including methods for providing a disruption force to trabecular tubule tissue, may be highly suitable for trabeculotomy and goniotomy, as they avoid the use of electrocautery and allow the elongated member to be advanced over a greater arc of Schlemm's canal. When the present systems and devices are adapted to provide a disruption force to trabecular tubule tissue, implant-free methods may be used, such as by delivering a disruption volume of viscoelastic fluid, advancing a disruption instrument, such as a cannula, elongated member, catheter, or both. In some examples, the disruption instruments may comprise a disruption component at their distal portions. Exemplary disruption components include, but are not limited to, notches, hooks, barbs, balloons, or combinations thereof. In other examples, the disruption instruments may not comprise a disruption component at their distal portions, and may in fact have an atraumatic blunt distal portion. Exemplary atraumatic distal portions include, but are not limited to, an umbrella or dome shaped distal portion.

[0173] In some variations of abinternotrabeculotomy and goniotomy, the procedure includes advancing a cannula at least partially through the anterior chamber of the eye, entering Schlemm's canal at a single access point using the cannula, and delivering a volume of viscoelastic fluid through an elongated member with a lumen and extendable from the cannula, sufficient to disrupt Schlemm's canal and surrounding tissue structures to reduce intraocular pressure. Another method that may be useful for treating an ocular condition includes entering Schlemm's canal using an elongated member extendable from a single operator-controlled handle with a fluid reservoir, and delivering a volume of viscoelastic fluid from the fluid reservoir through the elongated member by increasing pressure in the fluid reservoir, the delivered volume of viscoelastic fluid being sufficient to disrupt Schlemm's canal and surrounding tissue structures to reduce intraocular pressure. The disruption volume may be from about 2 μl to about 16 μl. In one variation, the disruption volume is about 4 μl of viscoelastic fluid. As mentioned above, in some instances, the aliquot volume may range from about 20 μl to about 50 μl or so. Fluid delivery based methods are described in more detail above.

[0174] If no fluid is used, and only a disruption instrument is used, the outer diameter of the elongated member or instrument may be sized to vary for disruption of tissue, similar to how fluid volume may be varied to vary the level of disruption. For example, an elongated member or instrument having an outer diameter in the range of about 50 to about 100 microns may be advanced through the canal to slightly expand the canal and disrupt or remove septa obstructing circumferential canalicular flow. An elongated member or instrument having an outer diameter in the range of about 100 to about 200 microns may do the above and may also initiate tensioning of the trabecular meshwork and adjacent canalicular tissue. An elongated member or instrument having an outer diameter in the range of about 200 to about 300 microns may be able to do the above, but may also create micro-tears in the trabecular meshwork and adjacent canalicular tissue and maximally expand the collector channel. An elongated member or instrument having an outer diameter in the range of about 300 to about 500 microns may maximally disrupt tissue and create tears or perforations along the entire trabecular meshwork and adjacent canalicular tissue. Additionally, the longer the elongate member or instrument is advanced through the canal, the greater the effectiveness of the procedure. For example, the elongate member or instrument may be advanced from the tip of the cannula out into the canal around a 30 degree arc of the canal (e.g., advanced about 3-4 mm from the cannula), advanced around a 60 degree arc of the canal (e.g., advanced about 6-8 mm from the cannula), advanced around a 90 degree arc of the canal (e.g., advanced about 10 mm from the cannula), advanced around a 120 degree arc of the canal (e.g., advanced about 15 mm from the cannula), advanced around a 180 degree arc of the canal (e.g., advanced about 20 mm from the cannula), or advanced around a full 360 degree arc of the canal (e.g., advanced about 36-40 mm from the cannula) for maximum effectiveness and maximum intraocular pressure reduction. In some variations, the elongate member may have a non-uniform outer diameter. For example, the elongate member may have a tapered outer diameter such that the outer diameter increases from the distal end to the proximal end.

[0175] In some variations, the methods disclosed herein may include advancing the elongated member (or instrument) around a 5-360 degree arc of Schlemm's canal. In some variations, the methods may include advancing the elongated member (or instrument) around a 360 degree arc of Schlemm's canal, around a 270 degree arc of Schlemm's canal, around a 120 degree arc of Schlemm's canal, around a 180 degree arc of Schlemm's canal, or around a 90 degree arc of Schlemm's canal. In yet further variations, the advancement of the elongated member (or instrument) may be around a 0-5 degree arc of Schlemm's canal, around a 30 degree arc of Schlemm's canal, or around a 60 degree arc of Schlemm's canal. Advancement may occur from a single access point in Schlemm's canal or from multiple access points in the canal. When providing a disruption force, it may be beneficial to advance the elongated member around a 180 degree arc of Schlemm's canal in both clockwise and counterclockwise directions from a single access point in the canal.

[0176] Depending on factors such as the type and severity of the condition being treated, the disruption force may be generated to partially or completely disrupt and / or remove the trabecular meshwork and may be adjusted by varying the instrument configuration. In some methods, the trabecular meshwork may be disrupted during advancement of the slidable elongate member. Also, the trabecular meshwork may be disrupted, partially torn, completely torn, and / or removed during advancement by using customization of the body segment of the elongate member proximal to the tip with one or more notches, barbs, or balloons that capture the meshwork as the distal tip is guided and advanced along Schlemm's canal. Additionally, implants with edges specifically designed to cut the meshwork may be used.

[0177] In yet another method, the trabecular meshwork may be disrupted during retraction of the slidable elongate member. Yet another method for disrupting tissue may include customizing the system (e.g., the elongate member, any catheter or wire, probe tip, etc.) to capture or grab the meshwork upon retraction after advancement through the canal is complete. This may be done using a wire with a bent tip, hooks, notches, or barbs on the end that advances through the lumen of the catheter and then hooks the meshwork upon retraction, tearing it along its length, or removing it all together, or just a metal or polymer wire or suture (without a catheter) whose tip (and / or body) may advance through Schlemm's canal without tearing the meshwork, but which is hooked, notched, or barbed so that it hooks, tears, and / or completely removes the meshwork upon retraction. 18C, the elongate member (1806) may be provided with a disruption instrument, e.g., a sharp-edged element (1808) that can cut or tear the trabecular meshwork while being retracted into the cannula (1800) and held stationary. Exemplary sharp-edged elements can be hooks, wires, or any other suitable shape-memory components that can extend from the cannula to tear, cut, or remove the trabecular meshwork.

[0178] Another method for disrupting tissue may include using an oversized elongate member (e.g., one with an outer diameter of 300-500 microns) to tear the meshwork during delivery, or expanding or enlarging the elongate member after it has been fully advanced into Schlemm's canal to pull, disrupt, tear, or completely tear the meshwork. For example, using a catheter / elongate member, probe, or wire (with or without a lumen) having an outer diameter of 200-250 microns at the tip, but having a shaft that begins to flare outward up to about 300, up to about 400, or up to about 500 microns 3 hours into Schlemm's canal (i.e., at about the 5 or 10 mm mark of the catheter / elongate member), so that as the tip advances comfortably into Schlemm's canal, the enlarged shaft follows behind, disrupting the trabecular meshwork as it advances.

[0179] Alternatively, cutting, disrupting, removing, etc., the trabecular meshwork may be accomplished by tearing the meshwork by removing the cannula from the eye while leaving the elongated member in the canal. With reference to FIG. 18A, a cannula (1800) may be inserted into the anterior chamber (1802) and Schlemm's canal (1804), and an instrument (e.g., a slidable elongated member (1806)) may be advanced within the canal (1804). As shown in FIG. 18B, the cannula (1800) may be removed from the anterior chamber (1802) without retracting the elongated member (1806). This action may itself tear the trabecular meshwork. When the cannula (1800) is removed from the anterior chamber (1802), the elongate member (1806) may begin to tear the trabecular meshwork from the point where the cannula (1800) was inserted into Schlemm's canal (1804) and may continue to tear around the trabecular meshwork toward the distal end of the elongate member.

[0180] A variation of the method described herein is illustrated in Figures 29A-29D, which may be performed using a delivery system such as that described with respect to Figures 23A-23F. Figure 29A shows a flow chart illustrating the method. The method may be used to access the trabecular outflow system using a single clear corneal incision, allowing for up to 360 degrees of transluminal trabeculotomy. The method may use a flexible elongate member that may be advanced and stored using a single-handed disposable manual instrument. First, the device may be removed from the package. The lock is then removed from the delivery system. The cannula may be advanced into the anterior chamber through an existing corneal or scleral incision. It may be desirable for the incision to be at least about 1 mm wide. The distal tip of the cannula may be used to puncture the trabecular meshwork and enter Schlemm's canal. The cannula may be held stationary against the angle while the flexible elongate member is advanced into Schlemm's canal. One or more exposed portions of the wheel may be rotated proximally such that the flexible elongate member advances around Schlemm's canal a maximum of about 180 degrees (about 20 mm of circumferential canal movement). At this point, the flexible elongate member may be fully extended and the wheel may be unable to rotate any further. Visualization of the cannula tip by direct microscopy or gonioscopically may be maintained during this procedure, and the anterior chamber may be maintained by viscoelastic or continuous balanced salt solution infusion.

[0181] As the flexible elongate member advances, the cannula may be removed from the eye through the incision without retracting the flexible elongate member. This may cause the flexible elongate member to cut through the trabecular meshwork. In some instances, it may be desirable to bias the distal tip of the cannula toward the trabecular meshwork to be cut, which in some instances may help prevent the flexible elongate member from slipping out of the canal during removal of the cannula. Removal of the cannula (2900) without retraction of the flexible elongate member (2902) to tear the trabecular meshwork (2904) is illustrated in FIGS. 29B-29D. As can be seen there, the elongate member (2902) translates the force from removal of the cannula (2900) into a force that tears the trabecular meshwork. Removal of the cannula (2900) creates an "unzipping" effect that tears the trabecular meshwork. That is, the trabecular meshwork is torn from its proximal end to its distal end by the body of the elongate member (2902). Initially, the force on the trabecular meshwork from the proximal end of the body of the elongate member (2902) causes the meshwork to tear near the insertion point of the cannula (2900). As the cannula (2900) continues to be withdrawn from the eye, the body of the elongate member (2902) continues to tear through the trabecular meshwork toward the distal tip of the elongate member, as shown in FIGS. 29C and 29D. Note that in this manner, the trabecular meshwork is torn progressively from a first location (the proximal end of the extended elongate member, near the insertion point of the cannula) to a second location (the distal end of the extended elongate member), as opposed to being cut or torn simultaneously along the distance from the first location to the second location. Further, it should be noted that in this method, each portion of the trabecular meshwork is not torn by a single feature of the elongated member (e.g., the distal end of the elongated member during advancement or retraction), but rather each portion of the trabecular meshwork is torn by the portion of the elongated member adjacent to it after the elongated member is advanced.

[0182] After the delivery system is completely removed from the eye, the flexible elongate member may be retracted back into the cannula by rotating one or more of the wheels distally. Once the flexible elongate member is completely retracted, the delivery system may be inverted so that the cannula tip rotates 180 degrees to face the opposite direction. The cannula tip may then be advanced through the corneal or scleral incision into the anterior chamber, and the distal tip may be advanced into the same entry point into Schlemm's canal. The above method may then be repeated for the second half of Schlemm's canal to sever the trabecular meshwork. In some instances, a viscoelastic material may be used to tamponade any reflux of blood back into the anterior chamber.

[0183] At the end of the procedure, the anterior chamber may be irrigated (e.g., with balanced salt solution) through the corneal wound (manually or automatically). Balanced salt solution or viscoelastic substances may be used to reshape the anterior chamber as needed to achieve physiological pressure and to further tamponade any backflow of blood from the collector channel back into the anterior chamber. If necessary, sutures may be used to seal the corneal or scleral incisions. Postoperatively, antibiotics or antiseptics, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for several weeks or months to help prevent adhesion formation and angle closure.

[0184] In yet a further method, tissue disruption may be achieved by abinterno delivery of a suture through Schlemm's canal, which is then pulled sufficiently to tension the canal, disrupt the trabecular meshwork, and / or tear through the meshwork ("abinterno suture trabeculotomy"). Here, an instrument including a grasping element may be used to sever the entire 360 ​​degrees or segment of the trabecular meshwork by pulling the distal suture ends inward as the cannula is withdrawn from the eye, or to tie the suture ends together to provide tension to the meshwork without having to tear it.

[0185] Abexterno Method The ab externo technique for implanting an intraocular device or delivering a fluid composition may include additional or slightly different steps. For example, creating a tissue flap, suturing, etc. may be part of the ab externo procedure. In general, the ab externo procedure for implanting an intraocular device may include the following steps: First, under microscopic visualization, the conjunctiva is incised, a scleral flap is created, and the tissue is dissected to identify the ostium to Schlemm's canal. The anterior chamber may be separately infused with saline or a viscoelastic composition may be placed therein to prevent the anterior chamber angle from collapsing. This operation may be performed as an independent procedure or may be combined with cataract surgery at once. It may also be performed before or after the cataract surgery portion.

[0186] Using the delivery system described herein, the cannula may be advanced into Schlemm's canal and the intraocular device may be advanced using the positioning element, either under direct microscopic visualization or through a gonioscopic or gonioprism. When the intraocular device has been advanced the desired amount, the surgeon may release the intraocular device from the positioning element by activating the engagement mechanism and remove the delivery system from the eye and surgical field. The scleral wound may be self-sealing, or it may be closed using, for example, sutures or tissue adhesives. If repositioning of the intraocular device is required or desired, the surgeon may use the positioning element of the delivery system to retract and / or advance the intraocular device.

[0187] For the delivery of the fluid composition, the ab externo method is similar to the ab interno delivery. However, instead of using a positioning element, the delivery system uses a slidable elongated member to inject the fluid composition into Schlemm's canal. First, under microscopic visualization, the conjunctiva is incised, a scleral flap is created, and the tissue is dissected to identify the ostium to Schlemm's canal. The anterior chamber may be separately injected with saline or a viscoelastic composition may be placed therein to prevent the anterior chamber angle from collapsing. This operation may be performed as an independent procedure or may be combined with cataract surgery at once. It may also be performed before or after the cataract surgery portion.

[0188] Using the delivery system described herein, a cannula may be advanced into Schlemm's canal and an elongated member disposed coaxially within the lumen of the cannula may be advanced into the canal under gonioscopic visualization. Once the elongated member is positioned within the canal, a fluid composition, e.g., a viscoelastic fluid, may be delivered continuously or intermittently through the elongated member. The fluid composition may exit the lumen of the elongated member through its distal end (e.g., through the distal tip), or through openings or fenestrations provided along its shaft, or a combination of both. The openings or fenestrations may be spaced along the axial length of the elongated member in any suitable manner, e.g., symmetrically or asymmetrically along its length. If desired, other substances such as drugs, air, or gas may be delivered in the same manner. The elongated member may be retracted or repositioned by repeated advancement and retraction. The delivery system may then be removed from the eye.

[0189] The configuration of the present intraocular delivery system can be advantageous in many different ways. In one embodiment, the present delivery system can be used in an abinterno method of implanting an intraocular device into Schlemm's canal or delivering a fluid composition or instrument to the canal. In another embodiment, the cannula of the delivery system is configured to allow easy and atraumatic access to Schlemm's canal. Furthermore, the present delivery system is configured in a manner that gives the surgeon more freedom of use, all with a single instrument. For example, the handle of the present system is configured to be used with either side up (i.e., by flipping the handle or rotating the cannula). Thus, the present delivery system is designed to be used in either hand, in either eye, in a clockwise or counterclockwise direction. For example, the present delivery system can be used with either hand, in either eye, to access Schlemm's canal in a counterclockwise manner, or with either hand, in either eye, to access the canal in a counterclockwise manner. Thus, access to the canal from all four quadrants of the eye can be achieved. In yet a further aspect, the delivery system comprises a single-handed, operator-controlled device configured to provide sufficient force to disrupt Schlemm's canal and surrounding tissue to improve flow through the trabecular outflow tract. The system generally combines the access cannula, delivery elongate member, elongate member advancement mechanism, disruption instrument, and viscoelastic fluid into a single device such that the elongate member or instrument can be advanced or fluid can be delivered by one person or one hand.

[0190] Method for manufacturing a cannula As mentioned above, the cannulas described herein may be configured to both pierce the trabecular meshwork or other tissue and reversibly deliver the elongate member without cutting, breaking, or damaging the elongate member. To accomplish these two objectives, the cannulas may be manufactured with a distal end having both a pointed portion and a blunt or rounded portion. Generally, the method of manufacturing the cannulas described herein may include creating a bevel at the distal tip of the cannula, sharpening the distal end of the distal tip to create a pointed puncturing tip, blunting a portion of the distal tip of the cannula, and bending a portion of the cannula along the longitudinal axis of the cannula. In some variations, the method may also include obtaining a suitable working length of the cannula, roughening the exterior surface of the cannula, applying a protective cover to a portion of the distal tip, polishing a portion of the cannula, and cleaning the cannula.

[0191] FIG. 19 illustrates an exemplary method of manufacturing a cannula for use with the devices, systems, and methods described herein. As shown therein, a method of manufacturing a cannula (1900) may include obtaining a cannula of an appropriate working length (1902), roughening the exterior surface of the cannula (1904), creating a bevel at the distal tip of the cannula (1906), sharpening the distal tip of the cannula (1908), applying a protective covering to the distal tip of the cannula (1910), smoothing a portion of the distal tip of the cannula (1912), bending the cannula (1914), polishing the cannula (1916), and cleaning the cannula (1918). Although the method steps in FIG. 19 are shown in a particular order, it should be understood that many of the steps may be completed in a different order and some of the steps may be optional altogether, as discussed in more detail below.

[0192] To begin the process, a cannula of a suitable working length may be obtained (1902). The cannula may be purchased pre-cut to the desired working length, or the raw material used to create the cannula, e.g., stainless steel hypodermic tubing, may be purchased in bulk and cut to the appropriate length during the cannula manufacturing process. The cannula may be inspected for breaks or other visible defects upon receipt and throughout the manufacturing process. In some variations, the working length (i.e., a length suitable for handling the cannula during manufacturing) may correspond to the desired final length of the cannula. In other variations, e.g., for ease of manufacturing, the working length may be longer than the desired length, and the cannula may be cut or shortened (e.g., by cutting the proximal end of the cannula) to the desired final length at any point during the manufacturing process, including the final step of the process. Exemplary working lengths include, but are not limited to, about 50 mm to about 70 mm, about 40 mm to about 90 mm, and more specifically, about 60 mm.

[0193] The proximal end of the cannula may be cut, treated, and / or finished at any time during the manufacturing process. In some instances, the proximal end of the cannula may be square cut (i.e., cut substantially perpendicular to the longitudinal axis of the cannula). The edges of the proximal end may be smoothed or rounded using any suitable method, for example, by media jetting. This smoothing of the proximal end of the cannula may prevent cutting, tearing, or damaging the elongate member. For example, smoothing of the proximal end may remove any sharp edges or wavy surfaces from the proximal end and remove any debris or deposits remaining at the proximal end of the lumen from the cutting process. The proximal end of the cannula may be inspected after smoothing, and if sharp or serrated edges remain, the proximal end may be further smoothed.

[0194] In some variations, the outer surface of the cannula may be optionally roughened (1904) or textured, which may aid in adhesion of the cannula to the handle. For example, in some instances, a proximal or central portion of the outer surface of the cannula may be abrasively jetted to create a textured or roughened surface to which adhesive may be applied. By abrasively jetting the outer surface of the cannula, the surface area of ​​the abrasively jetted portion is increased, which may provide better adhesion between the handle and the cannula.

[0195] As discussed above, the distal end of the cannula may be beveled. The bevel may be created by cutting or grinding the distal end of the cannula at an angle relative to the longitudinal axis of the cannula (1906). More specifically, the bevel may be located to traverse and be perpendicular to the lumen of the cannula. FIG. 3 shows a side view of a cannula (300) with a bevel (312) at its distal tip (306). The bevel (312) may have an angle (A) of about 5 degrees to about 85 degrees. As discussed above, the angle (A) may be important to properly pierce the trabecular meshwork and access Schlemm's canal without damaging other surrounding tissue, and / or to adequately visualize the advancement and retraction of the elongate member. In some variations, angle (A) may be about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 85 degrees. In some variations, angle (A) may be about 23 degrees to about 27 degrees. In some of these variations, angle (A) may be about 25 degrees.

[0196] FIG. 20 shows a perspective view of the distal tip (2002) of the cannula (2000) after creating a bevel. As shown, the beveled distal tip (2002) now comprises a proximal end (2008) and a distal end (2010). In addition, creating a bevel at the distal tip (2002) elongates the opening (2012) at the distal tip (2002), creating an elliptical shaped opening rather than a circular opening. Thus, beveling the distal tip (2002) may result in an elliptical shaped lumen opening, with the top of the elliptical opening sloping closer to the proximal portion of the cannula than the bottom of the elliptical opening. The inner and outer periphery edges (2004, 2006) are also shown in FIG. 20.

[0197] Although the placement of the bevel may create a sharp edge and, in some instances, a sharp distal tip, it may be desirable to further sharpen a portion of the distal tip of the cannula to achieve easier access to Schlemm's canal with greater precision. Thus, in some instances, after creating the bevel, the distal tip may be further sharpened (1908) to create a sharp puncturing tip that may further assist in puncturing the trabecular meshwork. The distal tip may be sharpened using any suitable technique, for example, by grinding or removing a portion of the outer surface and / or a portion of the outer periphery of the distal end of the distal tip of the cannula. To minimize undesirable sharp edges that may damage the elongate member, it may be desirable to maintain the wall thickness at the distal tip as thick as possible and ensure that the wall thickness is uniform. It may be beneficial to prevent cannula material or other sharpening by-products from forming, accumulating, adhering, or depositing on the inner surface of the cannula within the lumen. Such material may fragment and create raised or sharp surfaces or edges that may cut or damage the elongate member during use of the delivery system.

[0198] 21A and 21B show perspective and front views, respectively, of a variation of a cannula distal tip (2100) that includes both a bevel (2102) and a sharp piercing tip (2114). The distal tip (2100) also includes a proximal end (2108), a distal end (2110), inner and outer periphery edges (2104, 2106), and a lumen opening (2112). The sharp piercing tip (2114) may be created by sharpening the distal end (2110) of the distal tip (2100), thereby creating two beveled surfaces (2116) that meet to form a sharp point. The beveled surfaces (2116) may be formed at any suitable angle that results in a sharp piercing tip (2114). For example, in some instances, the beveled surface (2116) may have an angle (B) relative to the longitudinal axis of the distal tip (2100) of about 20, 25, 30, 35, 40, 45, or 50 degrees, about 25 to about 50 degrees, or about 37.5 to about 42.5 degrees. Thus, in some variations, the angle between the two beveled surfaces (2116) may be about 50 to about 100 degrees. Although the distal tip (2100) is shown with two beveled surfaces, it should be understood that a distal tip having a single beveled surface may also be used.

[0199] Returning to FIG. 19, the method (1900) for manufacturing a cannula may further include blunting a portion of the distal tip (1912) of the cannula. In variants in which the distal tip of the cannula is pointed, the method may further include applying (1910) a protective covering over the pointed portion of the distal tip, e.g., the distal end of the pointed piercing tip (2114) and / or the beveled surface (2116), prior to blunting (1912) of the distal tip, as described above with respect to FIGS. 21A and 21B. In variants in which the distal tip is not pointed after beveling, it may still be desirable to apply a protective covering over the distal end of the distal tip (as described above with respect to FIG. 20). The application of a protective covering may help maintain the sharp edge(s) during blunting.

[0200] As mentioned above, the distal tip of the cannula may be configured to both puncture tissue and deliver the elongate member. The elongate member itself may be susceptible to puncture, cutting, shearing, or damage by the cannula. To protect the elongate member, it may be important to smooth or chamfer the surfaces and / or edges of the distal tip of the cannula with which the elongate member may come into contact. For example, referring again to FIGS. 21A and 21B, in some variations, portions of the inner and / or outer periphery edges (2104, 2106), the surface (2118) between the edges, and / or the inner and / or outer surfaces of the cannula adjacent the opening (2112) may be smoothed. This may make these edges and surfaces uniform and / or blunt. For example, it may be desirable to smooth a portion of the inner periphery edge (2104) at the proximal or distal ends (2108, 2110) of the distal tip (2100), or to smooth the entire inner periphery edge. In some examples, a portion of the outer circumferential edge (2106) may also be smoothed while maintaining a sharp edge (e.g., a sharp piercing tip) of the distal 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) may be smoothed up to the beveled surface (2116). In addition, it may be desirable to smooth or chamfer the surfaces between the edges (2118) and / or the inner or outer surfaces of the cannula adjacent or circumferentially around the opening (2112) at the proximal end (2108) or distal end (2110) of the distal tip (2100).

[0201] A portion of the distal tip (2100) of the cannula may be beveled, smoothed, evened out, rounded, blunted, or the like using any suitable mechanism. For example, smoothing a portion of the distal tip of the cannula may include mechanical and / or manual beveling, abrasive or soda media blasting, filing, sharpening, wire brushing, laser ablation, polishing (e.g., electrolytic polishing), combinations thereof, or the like.

[0202] Returning to FIG. 19, the method of making the cannula (1900) may further include bending a distal portion of the cannula (1914) to form the distal curved portion described above. Bending the catheter may allow the distal tip to be properly oriented to atraumatically pierce the trabecular meshwork. Returning to FIG. 3, in some variations, the distal portion of the cannula may be bent such that the sharp piercing tip lies along the outer radius (322) of the curved cannula. In some examples, the distal portion of the cannula may be bent at an angle of about 100 to about 125 degrees, about 115 to about 125 degrees, or about 118 degrees relative to the outer surface of the proximal portion of the cannula.

[0203] The distal portion of the cannula may be bent using any suitable mechanical or manual bending process. It may be important to select a bending process that does not alter the cross-sectional size and shape of the cannula during the bending process. In addition, it should be understood that the cannula may be bent at any point during the manufacturing process and that bending does not necessarily have to occur after smoothing of the distal tip of the cannula, as shown in method (1900) in FIG.

[0204] The method of manufacturing the cannula (1900) may optionally include grinding all or a portion of the cannula, for example, the distal tip of the cannula (1916). In variations in which the cannula is ground, grinding the cannula (1916) may remove any remaining debris, markings, nicks, grooves, or the like on the surface of the cannula. These markings may be artifacts from any part of the manufacturing process, particularly from creating a bevel at the distal tip of the cannula (1906), sharpening the distal tip of the cannula (1908), and / or smoothing a portion of the distal tip of the cannula (1912). Grinding the cannula (1916) may be particularly useful in variations involving processes in which smoothing a portion of the distal tip of the cannula (1912) generally leaves behind debris or markings, for example, laser ablation. Polishing the cannula (1916) may be completed using any suitable method, such as electropolishing, staged media jetting using media of increasing particle size, or the like.

[0205] If desired, cleaning (1918) of the cannula may be performed prior to placement in a delivery system described herein. For example, in some variations, the cannula may be passivated to remove iron oxide or other contaminants. In some examples, the cannula may be passivated using an acid, such as nitric oxide. In other variations, the cannula may be cleaned using a detergent, an ultrasonic bath, or any suitable cleaning process.

[0206] The cannula and / or assembled delivery system may be sterilized, for example, using gamma irradiation. The dose range for gamma irradiation may be, for example, 25-40 kGy. Other radiation energies, for example, E-beam irradiation, may be used for sterilization. Alternative sterilization methods include gas sterilization, for example, ethylene oxide gas sterilization. In variations in which all or part of the system is reusable, these parts may be sterilized and reused as described herein. For example, in variations in which the handle is reusable and the cannula and elongate member are disposable, after use, the used cannula and elongate member may be removed, the handle sterilized, and new cannula and elongate member attached to the sterilized handle.

[0207] While the inventive devices, systems, kits, and methods have been described in some detail for purposes of illustration, such illustration is for purposes of clarity of understanding only. In light of the teachings herein, it will be readily apparent to those of ordinary skill in the art that certain changes and modifications can be made thereto without departing from the spirit and scope of the appended claims.

Claims

1. A device for treating an ocular condition, comprising: Housing and a cannula coupled to a distal end of the housing; an elongate member configured to be advanced into Schlemm's canal, the elongate member comprising an internal lumen; a fluid reservoir fluidly coupled to the lumen of the elongate member, the fluid reservoir terminating at a proximal end with a proximal opening therein, the proximal opening including a seal; Equipped with The device is configured to receive a fluid composition into the fluid reservoir through the sealing portion and deliver the fluid composition from the fluid reservoir through the elongate member and into Schlemm's canal.

2. The device described in claim 1, wherein the sealing portion is configured to be opened using a filling tool.

3. The device described in claim 1, wherein the sealing portion is configured to bias and close the proximal opening.

4. The device described in claim 1, wherein the sealing portion comprises a ball bearing, a gasket, and a spring configured to close the proximal opening of the fluid storage portion by pushing the ball bearing into the gasket.

5. The device described in claim 1, further comprising a linear gear and a ratchet, the ratchet being located between the fluid storage portion and the linear gear.

6. The device described in claim 5, wherein the linear gear and the ratchet are configured to move together during advancement of the elongated member.

7. The device described in claim 5, wherein the linear gear is configured to move relative to the ratchet during delivery of the fluid composition to Schlemm's canal.

8. The device described in claim 5, wherein the elongated member is configured to be retracted simultaneously with delivery of the fluid composition to Schlemm's canal, and the linear gear is configured to move relative to the ratchet during retraction of the elongated member.

9. The device described in claim 5, wherein the linear gear is coupled to a rotary component, and rotation of the rotary component in a first direction moves the linear gear relative to a housing.

10. The device described in claim 9, wherein rotation of the rotary component in the first direction advances the elongated member.

11. The device described in claim 9, wherein rotation of the rotary component in a second opposite direction moves the linear gear relative to the ratchet.

12. The device described in claim 11, wherein rotation of the rotary component in the second direction retracts the elongated member.

13. The device described in claim 5, wherein the ratchet and the linear gear are at least partially contained within the housing.

14. The device described in claim 5, wherein the elongated member is configured to be retracted simultaneously with delivery of the fluid composition to Schlemm's canal, and the fluid reservoir is fixed relative to the housing during retraction of the elongated member.

15. The device described in claim 5, further comprising a fluid assembly including the fluid reservoir, and the ratchet is coupled to the fluid assembly.

16. A device as described in claim 5, wherein the distal end of the ratchet is movably positioned within a track in the linear gear.

17. The device described in claim 16, wherein the track has one or more teeth configured to resist movement of the distal end of the ratchet within the track.

18. The device described in claim 1, wherein the volume of the fluid composition delivered from the fluid reservoir corresponds to the amount of movement of the elongated member toward the storage position.

19. The device described in claim 1, wherein the cannula has a distal tip, and the elongated member further has a distal end that is slidable within the cannula between a stored position and an extended position, and the distal end of the elongated member is within the cannula in the stored position and is distal to the distal tip of the cannula in the extended position.

20. The device of claim 1, further comprising a plunger having a proximal end, a distal end, and an inner cavity, the proximal end of the plunger being slidably positioned within the fluid reservoir.

21. The device of claim 1, wherein the device is configured to deliver between about 1 microliter and about 50 microliters of the fluid composition outside the lumen of the elongated member.

22. A device for introducing a fluid composition into Schlemm's canal, comprising: Housing and a cannula coupled to a distal end of the housing; a flexible elongate member configured to be advanced into Schlemm's canal, the flexible elongate member comprising an internal lumen; a fluid reservoir fluidly coupled to the lumen of the flexible elongate member, the fluid reservoir terminating at a proximal end with a proximal opening therein, the proximal opening including a seal and configured to receive a fluid composition therethrough; a drive assembly including a linear gear, the drive assembly configured to advance and retract the flexible elongate member by moving the linear gear relative to the housing and the fluid reservoir; A device comprising:

23. The device of claim 22, wherein the seal is configured to be opened using a filling tool.

24. The device described in claim 22, wherein the sealing portion is configured to bias and close the proximal opening.

25. The device described in claim 22, wherein the sealing portion comprises a ball bearing, a gasket, and a spring configured to close the proximal opening of the fluid storage portion by pushing the ball bearing into the gasket.

26. The device of claim 22, further comprising a ratchet positioned between the linear gear and the fluid reservoir.

27. The device described in claim 26, wherein the drive assembly is configured to advance the flexible elongated member by moving the linear gear and the ratchet together.

28. The device described in claim 26, wherein the drive assembly is configured to store the flexible elongated member by moving the linear gear relative to the ratchet.

29. The device described in claim 22, wherein the cannula has a distal tip, and the flexible elongate member further has a distal end that is slidable within the cannula between a retracted position and an extended position, and the distal end of the flexible elongate member is within the cannula in the retracted position and is distal to the distal tip of the cannula in the extended position.

30. The device described in claim 22, wherein the drive assembly is configured to simultaneously retract the flexible elongated member and deliver the fluid composition.

31. The device described in claim 22, wherein translation of the linear gear in a first direction moves the flexible elongated member toward a storage position and delivers the fluid composition from the fluid storage portion through the inner cavity of the flexible elongated member.

32. The device described in claim 31, wherein translation of the linear gear in a second opposite direction moves the flexible elongated member toward an extended position.

33. The device described in claim 31, wherein the volume of the fluid composition delivered from the fluid reservoir corresponds to the amount of movement of the flexible elongated member toward the storage position.

34. The device described in claim 22, wherein the drive assembly further comprises a rotary component, rotation of the rotary component causing movement of the linear gear.

35. The device described in claim 22, wherein the device is configured to deliver the fluid composition contained in the fluid storage portion from the fluid storage portion to Schlemm's canal through the sealing portion.

36. The device of claim 35, wherein the device is further configured to tear or cut the trabecular meshwork.

37. The device described in claim 22, wherein the device is configured to deliver between about 1 microliter and about 200 microliters of the fluid composition outside the inner cavity of the flexible elongated member.

38. The device described in claim 22, further comprising a plunger having a proximal end, a distal end, and an inner cavity, the proximal end of the plunger being slidably positioned within the fluid reservoir.

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