Patent Publication Number: US-2022233354-A1

Title: System and method for delivering multiple ocular implants

Description:
RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/396,211, filed Apr. 26, 2019, which is a continuation of U.S. patent application Ser. No. 14/928,626, filed Oct. 30, 2015, now issued as U.S. Pat. No. 10,271,989, which is a continuation of U.S. patent application Ser. No. 14/387,657, filed Sep. 24, 2014, now issued as U.S. Pat. No. 9,173,775, which is a U.S. National Phase entry under 35 U.S.C. § 371 of International Application No. PCT/US2013/031636, filed Mar. 14, 2013, designating the United States and published in English on Oct. 3, 2013, as WO 2013/148275, which claims priority benefit of U.S. Provisional Application No. 61/615,479, filed Mar. 26, 2012, the entire contents of each of which are incorporated herein by reference. 
    
    
     FIELD 
     Embodiments of the inventions generally relate to intraocular pressure reduction and more specifically to systems, devices and methods for delivering multiple intraocular implants into the eye for treatment of ocular disorders. 
     BACKGROUND INFORMATION 
     A human eye is a specialized sensory organ capable of light reception and is able to receive visual images. Aqueous humor (hereinafter referred to as “aqueous”) is a transparent liquid that fills at least the region between the cornea, at the front of the eye, and the lens. Aqueous is continuously secreted by ciliary processes of a ciliary body to the posterior chamber of the eye and the aqueous flows to the anterior chamber by crossing the pupil, so there is a constant flow of aqueous humor from the ciliary body to the anterior chamber of the eye. The aqueous fluid supplies nutrients to the avascular structures of the eye (for example, the cornea and the lens) and maintains intraocular pressure. Pressure within the eye is determined by a balance between the production of aqueous and its exit through canalicular outflow, uveoscleral outflow, or other outflow routes or pathways. 
     Many open-angle glaucomas are caused by an increase in the resistance to aqueous drainage through the trabecular meshwork and/or Schlemm&#39;s canal (e.g., the canalicular outflow pathways). The tissue of the trabecular meshwork normally allows the aqueous to enter Schlemm&#39;s canal, which then empties into aqueous collector channels in the posterior wall of Schlemm&#39;s canal and then into aqueous veins, which form the episcleral venous system. The uveoscleral outflow pathways can refer to the aqueous leaving the anterior chamber by diffusion through intercellular spaces among ciliary muscle fibers or through a supraciliary and/or suprachoroidal space. 
     Intraocular implants (for example, shunts or stents can be implanted within the eye to facilitate the outflow of aqueous, thereby reducing intraocular pressure. Typical methods of implantation require relatively invasive surgical procedures, pose a risk of excessive trauma to the eye, and require excessive handling of the implant. For example, in a typical method of implantation, an incision is made through the sclera or cornea and the implant is inserted into the desired implantation location using forceps or another like manual grasping device. These forceps are configured for holding, and introducing into the eye only one implant at a time. This requires reloading and repositioning of the forceps prior to inserting each implant into the eye. Once the implants are deposited, the grasping device is removed and the incision is sutured closed. 
     Alternatively, a trocar, scalpel, or similar instrument can be used to pre-form an incision in the eve tissue before passing the implant into such tissue. After the incision is made in the eye tissue, a trocar can be advanced through the incision and then the implant can be delivered over the trocar. 
     Prior methods and systems for delivering multiple implants within the same eye typically require the delivery instrument to be removed from the eye and reloaded with a second implant. This reloading process increases the time of surgery, increases the risk of infection due to exposure and to excessive handling of the implant, and increases the risk of trauma to the eye due to multiple entries within an incision. 
     SUMMARY 
     A need exists for a more facile, convenient, less invasive, and less traumatic means of delivering multiple implants into the eye. In some embodiments of the present disclosure, a system and method for delivering multiple ocular implants at multiple implantation locations within internal eye tissue is provided that only requires a single incision within external eye tissue. In some aspects of the present disclosure, there is provided a system and method for delivering multiple ocular implants at a substantially constant speed and trajectory (e.g., velocity) at a specific controlled distance, thereby providing repeatability and consistency of deliveries within a single eye and of deliveries within multiple patients. 
     In accordance with some embodiments disclosed herein, a method of treating an ocular disorder is provided, comprising advancing an injector instrument loaded with multiple implants, sensors or other devices through an incision or opening in an eye and transmitting, transferring or otherwise delivering energy from an energy source to propel a first implant, previously loaded within or on the injector instrument, into eye tissue. The method also comprises repositioning the injector instrument and further transmitting or transferring energy from the energy source to propel a second implant, previously loaded within or on the injector instrument, into eye tissue at a second location spaced apart from the first location. The first and second implants are propelled at substantially the same speed, while the energy transmitted to propel the first implant out of the injector instrument to its implantation location is less than the energy transmitted to propel the second implant to its implantation location. In some embodiments, repositioning may be performed without removing the injector instrument from the eye. In some embodiments, the method comprises transmitting energy by unwinding or relaxing a torsion or non-torsion spring or by delivering energy from another stored energy or energy generation device (e.g., motor or electrical actuation device). 
     An injector instrument for treating an ocular disorder is disclosed in accordance with some embodiments disclosed herein. In some embodiments, the instrument comprises at least two implants loaded (e.g., pre-loaded) within or on the instrument. The instrument also comprises a source of energy for selectively releasing stored energy to deliver the implants into eye tissue and a cam operatively coupled to the source of energy that has a contoured profile configured to vary the amount of stored energy that is delivered to drive each implant out of the instrument to its implantation location. In some embodiments, the contoured profile of the cam may be the same for each implant delivery cycle. In some embodiments, the contoured profile of the cam may be different for each implant delivery cycle. 
     In accordance with sonic embodiments a system for treating an ocular disorder comprises an injector instrument, or applicator, and at least two pre-loaded implants arranged in series and being configured to be implanted within eye tissue (to allow fluid flow therethrough). The instrument also comprises a metering device configured to transfer energy to the implants for delivery at selected locations of the eye tissue. The metering device can be configured to meter a variable amount of energy transferred for each implant delivery event in the eye tissue. 
     In accordance with some embodiments an injector instrument for treating an ocular disorder comprises a trocar having a distal end configured to create openings in eye tissue. The instrument also comprises at least two implants loaded (e.g., pre-loaded) within the instrument. The implants comprise an inner lumen through which at least a portion of the trocar extends. The instrument further comprises a collet having a distal end spaced from the distal end of the trocar and having loaded therein at least some of the implants for delivery into eye tissue. The instrument also comprises an energy source operably coupled to the collet that is configured to release energy such that the distal end of the collet advances a respective one of the implants along the trocar and into the eye tissue, wherein the distance between the distal ends of the trocar and the collet can increase between each implant delivery cycle. In some embodiments, the distance between the distal ends of the trocar and the collet remain the same between each implant delivery cycle. 
     A delivery apparatus for implants is disclosed in accordance with some embodiments of the invention. The delivery apparatus comprises an incising member, multiple implants disposed in series along an axis of the incising member, and an injector mechanism configured to serially engage and drive each of the implants along the axis of the incising member. The incising member and the injector mechanism can, for example, be movable relative to each other from a first position, in which the incising member is positioned to cut eye tissue, to a second position, in which the incising member is moved proximally to inhibit the incising member from cutting. 
     A method for treating an ocular disorder is disclosed in accordance with some embodiments herein. In some embodiments, the method comprises providing an instrument having multiple implants preloaded thereon and advancing the instrument into an anterior chamber of an eye to locate a distal end of the instrument near a target implantation site. The method also comprises isolating a first implant and driving the isolated implant axially relative to the other implants using a driving member. The method further comprises implanting the first implant in eye tissue at the target implantation site using the driving member. The method also comprises implanting a second implant in eye tissue at another target implantation site. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other features, aspects, and advantages of the present disclosure will now be described with reference to the drawings of embodiments of the invention, which embodiments are intended to illustrate and not to limit the scope of the disclosure. 
         FIG. 1A  is a schematic cross-sectional view of an eye. 
         FIG. 1B  is an enlarged cross-sectional view of an anterior chamber angle of the eye of  FIG. 1A . 
         FIG. 2  is a perspective view illustrating an embodiment of a multiple-implant delivery apparatus. 
         FIG. 3  is a perspective exploded view of the multiple-implant delivery apparatus of  FIG. 2 . 
         FIG. 4A  is a side view of the left housing illustrated in  FIG. 3 . 
         FIG. 4B  is a longitudinal cross-section of the left housing of  FIG. 4A . 
         FIG. 5A  is a side view of the right housing illustrated in  FIG. 3 . 
         FIG. 5B  is a longitudinal cross-section of the right housing of  FIG. 5A . 
         FIG. 6A  is a side view of the needle assembly illustrated in  FIG. 3 . 
         FIG. 6B  is a longitudinal cross-section of the needle assembly of  FIG. 6A . 
         FIG. 7A  is a side view of the collet holder assembly of the multiple-implant delivery apparatus of  FIG. 2 , showing the collet holder, the collet return spring and the collet illustrated in  FIG. 3 . 
         FIG. 7B  is an enlarged perspective view of the collet holder illustrated in  FIG. 7A . 
         FIG. 7C  is a side view of the collet illustrated in  FIG. 7A . 
         FIG. 7D  is a longitudinal cross-section of the collet of  FIG. 7C . 
         FIG. 7E  is an enlarged longitudinal cross-section of the fingered sleeve of the collet of  FIG. 7D . 
         FIG. 8  is a side view illustrating an embodiment of a trocar assembly to be used in the multiple-implant delivery apparatus of  FIG. 2 . 
         FIG. 9  is a longitudinal cross-section of the needle end of the multiple-implant delivery apparatus of  FIG. 2 , showing multiple ocular implants ready for delivery. 
         FIG. 10  is a perspective view of the needle retraction button assembly illustrated in  FIG. 3 . 
         FIG. 11A  is a perspective view of the needle retraction button link illustrated in  FIG. 3 . 
         FIG. 11B  is a side view of the needle retraction button link of  FIG. 11A . 
         FIG. 12A  is a perspective view of the trigger button assembly illustrated in  FIG. 3 . 
         FIG. 12B  is a top view of the trigger button assembly of  FIG. 12 . 
         FIGS. 12C and 12D  are longitudinal cross-section views of the trigger button assembly of  FIG. 12B . 
         FIG. 13A  is a perspective view of the cam assembly of the multiple-implant delivery apparatus of  FIG. 2 . 
         FIG. 13B  is a side view of the cam assembly of  FIG. 13A . 
         FIG. 13C  is a transverse cross-section of the cam assembly of  FIG. 13B , in accordance with an embodiment. 
         FIG. 13D  is a partial cross-section of the cam assembly, showing a cam spring mounted on a cam, in accordance with an embodiment. 
         FIGS. 14A and 14B  illustrate the assembly and interaction between the internal components of the multiple-implant delivery apparatus of  FIG. 2 . 
         FIG. 15  is a schematic and partial sectional view of a portion of an eye illustrating insertion of the multiple-implant delivery apparatus  200  within the eye  100  using an ab interno procedure, in accordance with an embodiment. 
         FIGS. 16A-16E  illustrate the functional operation of the cam and the collet to effectuate delivery of multiple implants using the multiple-implant delivery apparatus of  FIG. 2 . 
         FIG. 17  illustrates how rotational movement of a cam with the contoured surface profile of  FIG. 16A  translates into lateral motion of a driving member, in accordance with an embodiment. 
         FIG. 18  is an enlarged schematic and partial sectional view of Schlemm&#39;s canal and the trabecular meshwork of an eye illustrating the position and operation of an ocular implant delivered by the multiple-implant delivery apparatus of  FIG. 2 . 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of systems, devices and methods for delivering multiple ocular implants are described herein. In the following description, numerous specific details are set forth to provide a thorough understanding of the embodiments; however, one skilled in the relevant art will recognize, based upon the disclosure herein, that the techniques described herein can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring certain aspects. 
     Reference throughout this description to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment described herein. Thus, the appearances of the phrases “in one embodiment” or “in certain embodiments” in various places throughout this description are not necessarily all referring to the same embodiments. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. 
       FIG. 1  A is a cross-sectional view of an eye  100 .  FIG. 1B  is an enlarged sectional view of the eye showing the relative anatomical locations of a trabecular meshwork  121 , an anterior chamber  120 , and Schlemm&#39;s canal  122 . With reference to  FIGS. 1A and 1B , the sclera  111  is a thick collagenous tissue that covers the entire eye  100  except a portion that is covered by a cornea  112 . The cornea  112  is a thin transparent tissue that focuses and transmits light into the eye and through a pupil  114 , which is a circular hole in the center of an iris  113  (colored portion of the eye). The cornea  112  merges into the sclera  111  at a juncture referred to as a limbus  115 . A ciliary body  116  is vascular tissue that extends along the interior of the sclera  111  from the outer edges of the iris in the limbal region to a choroid  117 . The ciliary body  116  is comprised of a ciliary processes and ciliary muscle. Ciliary zonules extend from the ciliary processes to a lens  126 . The choroid  117  is a vascular layer of the eye  100 , located between the sclera  111  and a retina  118 . An optic nerve  119  transmits visual information to the brain and is the anatomic structure that is progressively destroyed by glaucoma. 
     With continued reference to  FIGS. 1A and 1B , the anterior chamber  120  of the eye  100 , which is bound anteriorly by the cornea  112  and posteriorly by the iris  113  and the lens  126 , is filled with aqueous humor. Aqueous humor is produced primarily by the ciliary processes of the ciliary body  116  and flows into the posterior chamber, bounded posteriorly by the lens  126  and ciliary zonules and anteriorly by the iris  113 . The aqueous humor then flows anteriorly through the pupil  114  and into the anterior chamber until it reaches an anterior chamber angle  125 , formed between the iris  113  and the cornea  112 . 
     As best illustrated by the drawing of  FIG. 1B , in a normal eye, at least some of the aqueous humor drains from the anterior chamber  120  through the trabecular meshwork  121  via the canalicular route. Aqueous humor passes through the trabecular meshwork  121  into Schlemm&#39;s canal  122  and thereafter through a plurality of collector ducts and aqueous veins  123 , which merge with blood-carrying veins, and into systemic venous circulation. Intraocular pressure is maintained by an intricate balance between secretion and outflow of aqueous humor in the manner described above. Glaucoma is, in most cases, characterized by an excessive buildup of aqueous humor in the anterior chamber  120 , which leads to an increase in intraocular pressure. Fluids are relatively incompressible, and thus intraocular pressure is distributed relatively uniformly throughout the eye  100 . 
     As shown in  FIG. 1B , the trabecular meshwork  121  lies adjacent a small portion of the sclera  111 . Exterior to the sclera  111  is a conjunctiva  124 . Traditional procedures that create a hole or opening for implanting a device through the tissues of the conjunctiva  124  and sclera  111  involve extensive surgery, as compared to surgery for implanting a device, as described herein, which ultimately resides entirely within the confines of the sclera  111  and cornea  112 . 
     In accordance with some embodiments, an ophthalmic implant system is provided that comprises multiple ocular implants and a delivery instrument for delivering and implanting the multiple ocular implants within eye tissue. These ocular implants can be configured to drain fluid from the anterior chamber of a human eye into a physiologic outflow pathway, such as Schlemm&#39;s canal, aqueous collector channels, episcleral veins, the uveoscleral outflow pathway, the supraciliary space, and/or the suprachoroidal space. The physiologic outflow pathway can be an existing space or outflow pathway (such as Schlemm&#39;s canal) or a potential space or outflow pathway (such as the suprachoroidal space). In some embodiments, the ocular implants are configured to be delivered to a location such that the implant communicates or allows fluid to communicate with an outflow pathway. While this and other systems and associated methods and apparatuses may be described herein in connection with glaucoma treatment, the disclosed systems, methods, and apparatuses can be used to treat other types of ocular disorders in addition to glaucoma or to implant other devices (such as pressure sensors or analyte sensors (e.g., glucose sensors)). 
     While a majority of the aqueous leaves the eye through the trabecular meshwork and Schlemm&#39;s canal, it is believed that a significant percentage of the aqueous in humans leaves through the uveoscleral pathway. The degree with which uveoscleral outflow contributes to the total outflow of the eye appears to be species dependent. As used herein, the term “uveoscleral outflow pathway” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the space or passageway whereby aqueous exits the eye by passing through the ciliary muscle bundles located angle of the anterior chamber and into the tissue planes between the choroid and the sclera, which extend posteriorly to the optic nerve. From these tissue planes, it is believed that the aqueous travels through the surrounding scleral tissue and drains via the scleral and conjunctival vessels, or is absorbed by the uveal blood vessels. It is unclear from studies whether the degree of physiologic uveoscleral outflow is pressure-dependent or pressure-independent. 
     As used herein, the term “supraciliary space” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the portion of the uveoscleral pathway through the ciliary muscle and between the ciliary body and the sclera, and the term “suprachoroidal space” is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the portion of the uveoscleral pathway between the choroid and sclera. 
     The following description will include references to distal and proximal ends of various components and right and left sides of various components. The terms “distal” and “proximal” are to be given their ordinary and customary meaning to a person of ordinary skill in the art (and are not to be limited to a special or customized meaning), and refer without limitation to opposite regions or ends of a particular structure. In some embodiments, the term “distal” is used to refer to a region or end farther away from a person using the systems and devices described herein or performing the methods described herein and the term “proximal” is used to refer to a region or end closer to the person using the systems and devices described herein or performing the methods described herein; however, the meanings of the terms can be swapped. 
     The term “right side” should be understood to mean the side of the component that, upon assembly, faces the right housing of the multiple-implant delivery apparatus and the term “left side” should be understood to mean the side of the component that, upon assembly, faces the left housing of the multiple-implant delivery apparatus. However, these terms, as well as terms of orientation such as “top,” “bottom,” “upper,” “lower,” “front,” “rear,” and “end” are used herein to simplify the description of the context of the illustrated embodiments. Likewise, terms of sequence, such as “first” and “second,” are used to simplify the description of the illustrated embodiments. Because other orientations and sequences are possible, however, the claims should riot be limited to the illustrated orientations or sequences. Those skilled in the art will appreciate, upon reading this disclosure, that other orientations of the various components described above are possible. 
       FIGS. 2-13  illustrate a multiple-implant delivery apparatus, in accordance with embodiments of the invention.  FIG. 2  is a perspective view illustrating external components of a multiple-implant delivery apparatus  200 . As shown, the multiple-implant delivery apparatus  200  includes an external housing  202  comprising a distal end and a proximal end, with a main body extending therebetween. In the depicted embodiment, the distal end is gradually tapered to form a nose cone  204 , from which extends a needle  208 . As shown, the proximal end of the multiple-implant delivery apparatus  200  is also gradually tapered and can optionally include a label plate  210 , which can be secured to the external housing  202 , for example, by snapping, gluing, welding or other bonding methods. In certain embodiments, the label plate  210  is constructed of aluminum; however, it should be appreciated that the label plate  210  can be constructed of any rigid material (e.g. metal, plastic, or polymer). The label plate  210  can include, for example, a company or product name. External housing  202  further includes a button opening  212 , out of which protrudes a needle retraction button  214  and a trigger button  216  for actuation by a user. 
     The multiple-implant delivery apparatus  200  is advantageously ergonomically shaped for easy gripping and manipulation, and has a general overall shape similar to a conventional writing instrument, such as a fountain pen. In one embodiment, the multiple-implant delivery apparatus  200  can be grasped by the user between the thumb and the middle finger, with the index finger free to press the needle retraction button  214  and the trigger button  216 . In certain embodiments, tactile ridges (not shown) are provided on the external housing  202  in locations where the multiple-implant delivery apparatus  200  can be grasped to provide a more secure grip for the user. 
     In certain embodiments, the external housing  202  is fabricated from a plurality of separate sections configured to be attached together. For example, the nose cone portion  204  and the tail portion  206  can be manufactured as separate pieces that are then secured to the main body of the external housing  202 . In other embodiments, the external housing  202  is formed of two half-sections (as shown in  FIG. 3 ). 
     As described further herein, multiple ocular implants can be pre-loaded into or onto the needle  208  and the multiple-implant delivery apparatus  200  can be used to deliver the multiple ocular implants at various desired locations within a mammalian (e.g., human) eye. For example, the needle  208  can be advanced through a preformed incision or opening in the eye. In another embodiment, the needle  208  can be advanced through external eye tissue (e.g., the cornea, limbus and/or sclera), creating an incision or opening through the eye as it is advanced into the eye tissue. As further described below, depression of the trigger button  216  actuates the multiple-implant delivery apparatus  200  and causes the ejection of a first implant into a desired first location within the patient&#39;s internal eye tissue. In one embodiment, the multiple-implant delivery apparatus  200  can then be repositioned without removing the needle  208  from the incision and a second implant can be delivered to a second location spaced apart from the first location, another embodiment, the needle  208  can be removed from the incision and reinserted through eye tissue through a separate incision in order to deliver the second implant to the second implantation site. In accordance with several embodiments, the delivery of the multiple ocular implants advantageously is performed during an outpatient procedure without extensive surgery. 
     The combination of the overall external housing shape, together with the particular positioning of the needle retraction button  214  and the trigger button  216 , allows the user to control the positioning of the needle  208  and to maintain its stability primarily through manipulation of the thumb and middle finger. The index finger meanwhile controls actuation of the multiple-implant delivery apparatus, and thus the ejection of the implants from the needle  208  at the multiple desired locations within the eye. This design effectively separates positioning control from actuation control, thereby reducing the risk that ejecting the implants will inadvertently cause movement of the multiple-implant delivery apparatus  200  such that the actual placement of an implant is not at the desired location. 
     Structure of Multiple-Implant Delivery Apparatus 
       FIG. 3  is an exploded perspective view of the multiple-implant delivery apparatus  200 . The external components of the multiple-implant delivery apparatus  200  include a left housing  302 , a right housing  304 , a left fastener  305 A, a right fastener  305 B, and the label plate  210 . As shown, the external housing  202  is formed of two separate half-sections (left housing  302  and right housing  304 ). When assembled, the proximal ends of left housing  302  and right housing  304  are held together by left fastener  305 A and right fastener  305 B. In the depicted embodiment, the left fastener  305 A is a hexagonal shaped nut and the right fastener  305 B is a hexagonal shaped socket screw; however, other shapes and types of fasteners can be used as desired and/or required. The middle and distal ends of the left housing  302  and the right housing  304  can, in one embodiment, be configured to snap together via snap-fit members  308 A,  308 B disposed on each of left housing  302  and right housing  304 . Although the depicted embodiment shows fasteners  305 A,  305 B and snap-fit members  308 A,  308 B, other methods of fastening the two half-sections together are contemplated, including, for example, gluing, welding, fusing, Velcro, and adhesive bonding. In addition, in alternative embodiments, the external housing  202  could be separated into top and bottom half-sections instead of right and left half-sections. In yet other alternative embodiments, the external housing  202  is formed of more than two sections configured to be attached together to form a contiguous unit. 
     With continued reference to  FIG. 3 , the internal components of the multiple-implant delivery apparatus  200  include a needle assembly (including a needle holder  312  and the needle  208 ); a collet holder assembly  320  (including a collet holder  321 , a collet  322 , and a collet return spring  323 ); a trocar assembly  800  (shown in  FIG. 8 ); a needle retraction assembly (including a needle retraction button unit  332 , a needle retraction spring  334 , and a needle retraction link  335 ); a cam assembly (including a cam  341 , a cam spring  342 , and a cam dowel pin  343 ); and a trigger button assembly (including a trigger unit  351 , a trigger spring  352 , and a trigger dowel pin  353 ). 
     The internal components can be secured to or within the right housing  304  during assembly of the multiple-implant delivery apparatus  200  using various methods of fixation (e.g., adhesion, bonding, gluing, snap-fitting, and the like). The interaction of the internal components and the operation of the multiple-implant delivery apparatus will be discussed in more detail later in connection with  FIGS. 14-16 . 
     In certain embodiments, the multiple-implant delivery apparatus  200  is disposable and includes one or more safety mechanisms that prevent reuse. For example, the safety mechanism can be an internal component that renders the instrument inoperable if re-sterilized. For example, the safety mechanism can prevent reloading of implants, can prevent retraction of the needle after use, and/or can prevent the assembly that provides the energy to deliver the implants from being reused. In other embodiments, the multiple-implant delivery apparatus  200  can be reloaded with implants, sterilized, and re-used on the same or a different patient. 
       FIGS. 4A and 4B  illustrate the left housing  302  in more detail.  FIG. 4A  is a side view of the interior of the left housing  302  and  FIG. 4B  is a longitudinal cross-section of  FIG. 4A . The left housing  302  includes features for attachment to the right housing  304  and features for receiving the internal components of the multiple-implant delivery apparatus  200 . The attachment features include a left fastener slot  366 A and snap-fit members  308 A. The left fastener slot  366 A is sized and shaped to receive the left fastener  305 A, which in the illustrated embodiment of the multiple-implant delivery apparatus  200  of  FIG. 2  is a hexagonal-shaped nut. The left fastener slot  366 A is recessed within the left housing  302  so that the left fastener  305 A does not extend out beyond the exterior surface of the left housing  302  upon assembly and so that the left fastener  305 A remains securely in place. The snap-fit members  308 A of the left housing  302  include slots that are configured to receive and engage with tabs of corresponding snap-fit members  308 B of the tight housing  304 . 
     The receiving, or mounting, features of the left housing  302  include a left needle retraction spring mount  336 A, a left cam mount  344 A, a left trigger unit mount  354 A, the left half of a needle opening  408 , and the left half of the button opening  212 . The receiving features will be discussed in more detail in connection with the description of corresponding receiving features of the right housing  304 . 
       FIGS. 5A and 5B  illustrate the right housing  304  in more detail. The right housing  304  includes attachment and receiving features corresponding to those described in connection with the left housing  302 . For example, the attachment features of the left housing include a right fastener slot  366 B and snap-fit members  308 B. The right fastener slot  36613  is configured to receive the right fastener  305 B. In the depicted embodiment, the right fastener slot  366 B is circular in order to receive the right fastener  305 B, which in the depicted embodiment, is a screw with a circular head. The right fastener slot  366 B is recessed within the right housing  304  so that the right fastener  305 B does not extend out beyond the surface of the right housing  304  upon assembly and so that the right fastener  305 B remains securely in place during delivery and use. The snap-fit members  308 B include ridged tabs that are configured to snap into the slots of snap-fit members  308 A of the left housing  302 . In certain embodiments, there is an audible click when snap-fit members  308 A and snap-fit members  308 B are fully engaged. 
     The corresponding receiving, or mounting, features include a right needle retraction spring mount  336 B, a right cam mount  346 B, a right trigger unit mount  356 B, the right half of the needle opening  408 , and the right half of the button opening  212 . The right needle retraction spring mount  336 B is configured to align with the left needle retraction spring mount  336 A and together, the right and left needle retraction spring mounts  336  are sized and configured to receive and fixedly secure one end of the needle retraction spring  334 . The right cam mount  346 B is configured to align with the left cam mount  346 A and together, the right and left cam mounts  346  are sized and configured to receive the cam dowel pin  343 , which provides a mount and rotational pivot for the cam  341 . The right trigger unit mount  356 B is configured to align with the left trigger unit mount  356 A and together, the right and left, trigger unit mounts  356  are sized and configured to receive the trigger dowel pin  353 , which provides a mount and pivot for the trigger unit  351 . 
     The right housing  304  additionally includes various engagement members. The engagement members can include protrusions from the inner wall of the right housing  304  that engage portions of various internal components of the multiple-implant delivery apparatus  200 . For example, engagement member  555  engages the distal end of the trigger spring  352 , engagement member  345  engages one end of the cam spring  342 , and engagement member  325  engages the collet holder  321 . 
     In certain embodiments, the left housing  302  and the right housing  304  can be composed of any rigid or semi-rigid material, such as plastic, polymer, metal, composites, or the like. In certain embodiments, the left housing  302  and the right housing  304  are molded from Lexan® polycarbonate. In other embodiments, at least a portion of the left housing  302  and/or the right housing  304  can be composed of a flexible material, such as silicone or similar elastomeric or flexible polymers. 
       FIGS. 6A and 6B  illustrate an embodiment of a needle assembly  310  to be utilized with the multiple-implant delivery apparatus  200 .  FIG. 6A  is a side view of the right side of the needle assembly  310 .  FIG. 6B  is a longitudinal cross-section of  FIG. 6A . The needle assembly  310  includes the needle  208  and the needle holder  312 . In certain embodiments, upon assembly, the needle  208  is bonded to the needle holder  312  using an ultraviolet (“UV”) light-curing or other type of adhesive or bonding method; however, other attachment (e.g., bonding, welding, clamping, press-fitting) methods are contemplated. 
     In certain embodiments, the needle  208  is constructed of stainless steel and includes a needle tip  314  having a beveled, tapered, or otherwise sharpened edge oriented as shown in  FIG. 6A . The beveled edge can be formed at a standard 15-degree angle or other angles as desired and/or required. In certain embodiments, the needle  208  advantageously includes a tri-beveled edge for less traumatic insertion. The needle  208  can have a small diameter size so that the incision is self-sealing without suturing upon withdrawal of the needle  208  from the eye. In certain embodiments, an outer diameter of the needle  208  is preferably no greater than about 18-gauge and not smaller than about 27-gauge. In certain embodiments, the needle  208  can advantageously be a hollow 23-gauge needle with an outer diameter of about 0.025 inches and an inner diameter of about 0.0205 inches. However, the needle  208  can have other suitable dimensions. In certain embodiments, the needle  208  advantageously has a low-friction or lubricious coating on at least a portion of the needle  208 . In certain embodiments, the needle  208  advantageously has a hydrophobic coating, a hydrophilic coating, a hydrophilic coating, and/or other low-friction coating on at least a portion of the needle  208 . In certain embodiments, the coating is applied to the outside surfaces of the needle  208  (including the cutting features) but not on the inside surfaces. In some embodiments, the needle  208  is replaced with any suitable piercing member configured to create an incision in external eye tissue, such as a cannula, a scalpel and the like. 
     Besides holding the needle  208  in place, the needle holder  312  interfaces with the needle retraction link  335  to facilitate needle retraction. The needle holder  312  includes a needle retraction link slot  316  sized and shaped to match the profile of the distal end of the needle retraction link  335 . The needle holder  312  is formed of any rigid material, such as a plastic or polymer. In certain embodiments, the needle holder  312  is molded from VECTRA® liquid crystal polymer (“LCP”) manufactured by Ticona; however, other polymeric materials can be used as desired (for example, neoprene, nylon, polyvinyl chloride (PVC), polystyrene, polyethylene, polypropylene, polyacrylonitrile, silicone, polyvinyl butyral (PVB), acrylonitrile butadiene styrene (ABS)). The needle holder  312  extends from the needle  208  at an angle that is offset from the longitudinal axis of the needle  208 . 
       FIG. 7A  is a side view of an embodiment of a collet holder assembly  320  of the implant delivery device  200 . As shown, the collet holder assembly  320  includes the collet holder  321 , the collet  322 , and the collet return spring  323 . In certain embodiments, upon assembly, the collet  322  is bonded to the collet holder  321  using a UV light curing or other type of adhesive method; however, other bonding methods are contemplated (for example, bonding, welding, other adhesives, press-fitting). The collet return spring  323  is loaded onto the collet  322  during assembly. The collet return spring  323  can be a coil or helical spring (e.g., tension/extension or compression spring) constructed of stainless steel wire; however, metals other than stainless steel or polymeric materials can also be used as desired). In certain embodiments, the collet return spring  323  can advantageously be formed of coiled stainless steel wire having about a 0.006-inch wire diameter and a free length of about 0.5 inches and a spring diameter of about 0.08 inches; however, the collet return spring  323  can have other suitable dimensions as desired and/or required without limitation. In operation, the collet return spring  323  provides a bias force to the collet holder  321  that maintains engagement between the collet holder  321  and the contoured surface of the cam  341 . It should be appreciated that the collet return spring  323  can be replaced with any suitable mechanism for providing a bias force (for example, a torsion spring, a leaf spring, a non-torsion spring such as a compression spring, a flat spring, a hairspring, a balance spring, a V-spring, a volute spring, an elastomeric band, magnetic coupling, gas compression). 
       FIG. 7B  is an enlarged perspective view of the collet holder  321 . The collet holder  321  includes a cam follower  324  that engages and follows the contoured surface profile of the cam  341 . The collet holder  321  further includes an outer bore  325  sized and shaped for receiving an end of the collet return spring  323  and an inner bore  326  sized and shaped for receiving an end of the collet  322 . In certain embodiments, the outer bore  325  has a diameter of about 0.09 inches and the inner bore  326  has a diameter of about 0.026 inches; however, other suitable dimensions are contemplated (for example, the outer bore  325  can have a diameter between about 0.01 inches and about 0.20 inches and the inner bore  326  can have a diameter of about 0.001 inches and about 0.10 inches). The collet holder  321  is molded from Vectra® LCP manufactured by Ticona in certain embodiments; however, other polymeric materials can be used as desired (for example, neoprene, nylon, polyvinyl chloride (PVC), polystyrene, polyethylene, polypropylene, polyacrylonitrile, silicone, polyvinyl butyral (PVB), acrylonitrile butadiene styrene (ABS)). 
       FIGS. 7C-7E  illustrate the structural details of the collet  322 . The collet  322  can be a solid body  327  with a slotted sleeve  328 . The slotted sleeve  328  can have four fingers  329  bounded by four slits spaced  90  degrees apart from each other and having a length from about 0.05 inches to 0.25 inches; however, in other embodiments, the slotted sleeve  328  can have more or fewer fingers disposed at other angular spacings. In certain embodiments, the collet  322  is advantageously constructed of Nitinol (nickel titanium alloy) material; however, the collet  322  can be constructed of any suitable flexible material (for example, flexible metal or polymer). The slotted sleeve  328  can further include a beveled, or chamfered, edge to improve lateral movement of the collet  322  during operation of the multiple-implant delivery apparatus  200 . 
       FIG. 8  is a side view illustrating an embodiment of a trocar assembly  800  of the multiple-implant delivery apparatus  200  to deliver multiple ocular implants. The trocar assembly  800  includes a trocar  814  and a backup tube  816 . As shown, the cutting tip  818  can be beveled, tapered, and/or sharpened to facilitate insertion. The cutting tip  818  can form an implantation opening, or channel, in internal eye tissue (e.g. trabecular meshwork) into which an implant can be delivered. In one embodiment, the diameter of the trocar  814  is about 0.003 inches and the length is about 2.3 inches. In other embodiments, the diameter of the trocar  814  can be from about 0.001 inches to 0.01 inches and the length can be any suitable length to enable loading and delivery of multiple implants (for example, 0.5 inch to 5 inches). 
     The backup tube  816  includes a hollow tube having an inner diameter sized to receive the trocar  814 . In certain embodiments, backup tube  816  has an inner diameter of about 0.0035 inches; however, the backup tube  816  can have any inner diameter sized so as to receive the trocar  814 . As shown, the backup tube  816  can include a chamfered distal end  819 . In certain embodiments, the backup tube  816  is advantageously laser welded to the trocar  814  upon assembly. In other embodiments, the backup tube  816  can be bonded to the trocar  814  using other methods of fixation (for example, curing, welding, press-fitting, adhesive). 
     The trocar  814  can be angled or curved in certain embodiments. The trocar  814  can be rigid, semi-rigid, or flexible. In certain embodiments, some portions of the trocar  814  are flexible and other portions are rigid. In embodiments where the trocar  814  can be stiff the implant can be, but need not be relatively flexible. In certain embodiments, the trocar  814  and the backup tube  816  are advantageously constructed of stainless steel. In other embodiments, the trocar  814  and the backup tube  816  can be constructed of other suitable materials, such as other metals, plastics, or polymers. 
       FIG. 9  illustrates a longitudinal cross-section of the needle end  900  of the multiple-implant delivery apparatus  200 . As shown, four ocular implants  901  have been pre-loaded onto the trocar  814  during assembly. However, the multiple-implant delivery apparatus  200  can receive more or fewer than four implants for implantation into internal eye tissue. In certain embodiments, the ocular implants are disposed in series along a longitudinal axis of the trocar  814  (e.g., arranged in tandem). In various embodiments, upon assembly, the trocar  814  is retained within the collet  322 . In some embodiments, the trocar  814  can move longitudinally within the collet  322 . In other embodiments, the trocar  814  is fixed relative to the collet  322 . In various embodiments, upon assembly, the collet  322  is housed within an insertion tube  903 , which can be fixed relative to the trocar  814 . The insertion tube  903  can advantageously comprise a hollow hypodermic tube constructed of stainless steel. In alternative embodiments, the insertion tube  903  can be constructed of any rigid material, such as metal, plastic, or polymer. The internal diameter of the insertion tube  903  can range from about 0.005 inches to about 0.080 inches, from about 0.010 inches to about 0.030 inches, from about 0.015 inches to about 0.020 inches, from about 0.005 inches to about 0.040 inches, from about 0.020 inches to about 0.060 inches, or overlapping ranges thereof. 
       FIG. 10  is an enlarged perspective view of the needle retraction unit  332  illustrated in  FIG. 3 . The needle retraction unit  332  includes the needle retraction button  214 , a body  337 , and an anchor  338 . The needle retraction button  214  can advantageously include tactile ridges  339  to increase the friction between the user&#39;s finger and the needle retraction button  214  for ease of operation. The anchor  338  extends below the body  337  and is sized and shaped to interface with a corresponding slot of the needle retraction link  335  upon assembly. 
       FIGS. 11A and 11B  illustrate the needle retraction link  335 . The needle retraction link  335  is configured to interface with the needle holder  312 , the needle retraction unit  332 , and the needle retraction spring  334 , in order to enable retraction of the needle  208  for delivery of the implants within the eye tissue. The link  335  interfaces with the needle holder  312 , via the needle holder coupler  1116 . As shown, the needle holder coupler  1116  matches the profile of the needle retraction link slot  316  shown in  FIG. 6A . The link  335  interfaces with the anchor  338  of the needle retraction unit  332  via anchor slot  1138 , which is sized and shaped to receive the anchor  338 . The link  335  also interfaces with the distal end of the needle retraction spring  334  via retraction spring slot  1134 . The link  335  can be constructed of any rigid material, such as plastic or polymer. In certain embodiments, the link  335  is molded from Vectra® LCP manufactured by Ticona; however, other polymeric materials can be used as desired (for example, neoprene, nylon, polyvinyl chloride (PVC), polystyrene, polyethylene, polypropylene, polyacrylonitrile, silicone, polyvinyl butyral (PVB), acrylonitrile butadiene styrene (ABS)). 
       FIGS. 12A-12D  illustrate further structural details of the trigger unit  351 , which includes the trigger button  216 , a trigger spring coupling member  355 , a trigger dowel pin slot  356 , trigger button extensions  357 , and a trigger opening  358 . The trigger button  216  is sized and shaped to be pressed by a user&#39;s finger. In certain embodiments, the trigger button  216  includes tactile ridges or grooves to provide a more secure grip or feel for the user. 
     The trigger spring coupling member  355  is sized and shaped to be coupled to the proximal end of the trigger button spring  352 . In certain embodiments, the trigger button spring  352  can be a leaf spring constructed of a metal, such as stainless steel. The trigger button spring  352  can provide a bias force that returns the trigger button  216  to its initial non-depressed position after it is released by the user. The trigger button spring  352  can be replaced by any other suitable mechanism for providing a return bias force in other embodiments. 
     The trigger dowel pin slot  356  is sized and shaped to receive the trigger dowel pin  353  illustrated in  FIG. 3 . The trigger dowel pin  353  enables attachment of the trigger unit  351  to the external housing  202  and provides a pivot for the trigger unit  351 . In one embodiment, the trigger dowel pin  353  is made of stainless steel; however, any rigid material is contemplated (for example, a rigid metal or polymer). 
     The trigger button extensions  357  are sized and shaped to engage with corresponding engagement members protruding from the left housing  302  and the right housing  304  in order to prevent the trigger button  216  from being pressed too far down within the external housing  202 , thereby reducing potential interference with the operation of the internal components of the multiple-implant delivery apparatus  200 . 
     The trigger opening  358  is sized and shaped to receive and interface with the cam  341 . The trigger opening  358  includes a cam flat receiving slot  359 A, and a trigger stop  359 B. The triangular cam flat receiving slot  359 A and the trigger stop  359 B are sized and shaped to receive and temporarily engage flats disposed on the sides of the cam  341  (illustrated as  347  in  FIG. 13A ), thereby preventing further rotation of the cam  341  and deployment of more than one implant upon a single press of the trigger button  216 . In certain embodiments, the width of the trigger stop  359 B is from about 0.025 inches to about 0.25 inches; however, any suitable dimensions for engaging with the cam flats are contemplated. In certain embodiments, the trigger button unit  351  is formed of a contiguous, moldable plastic piece. For example, the trigger button unit  351  can be molded from Vectra® LCP manufactured by Ticona; however, other polymeric materials can be used as desired (for example, neoprene, nylon, polyvinyl chloride (PVC), polystyrene, polyethylene, polypropylene, polyacrylonitrile, silicone, polyvinyl butyral (PVB), acrylonitrile butadiene styrene (ABS)). 
       FIGS. 13A-13D  illustrate a cam assembly  340  in further detail.  FIG. 13A  is a perspective view of the cam  341  mounted on the cam dowel pin  343 . The cam  341  includes a cam huh  345 , a contoured cam profile  346 , and a plurality of cam flats  347 . The cam hub  345  is sized and shaped to receive the cam dowel pin  343 , which mounts the cam  341  to the external housing  202  and provides a rotational pivot for rotation of the cam  341 . In one embodiment, the cam dowel pin  343  is formed of stainless steel; however, other suitable rigid materials are contemplated. The contoured cam profile  346  controls the lateral movement of the collet  322 , which effects delivery of the individual ocular implants  901 . The operation of the cam  341 , and its effect on the lateral movement of the collet  322 , will be discussed later in connection with  FIGS. 16A-16E  and  FIG. 17 . In accordance with several embodiments, the implants are configured to be implanted at a substantially the same depth within the eye tissue at a specific distance from the distal end of the multiple-implant delivery apparatus  200 , which depth may be controlled by the structural features of the cam  341  described herein or other features or mechanisms. 
     As shown, the cam  341  can include five cam flats  347 . Four of the cam flats  347 B- 347 E can be positioned 90 degrees apart from each other. In operation, these four cam flats can be positioned to stop the rotation of the cam  341  when they abut against the trigger stop  359 B, thereby ensuring that only one implant is deployed when the trigger button  216  is pressed. The fifth cam flat  347 A can mark the starting point of cam rotation and can assist with the initial alignment of the cam  341  within the cam opening  358  of the trigger button unit  351  upon assembly. Upon assembly, the trigger stop  359 B is placed between cam flat  347 A and cam flat  347 B, thereby ensuring proper initial alignment. 
       FIG. 13B  is a side view of the right side of the cam  341 . Alignment mark  349  facilitates the initial alignment of the cam  341  with the cam follower  324  on the collet holder  321  during assembly.  FIG. 13C  is a transverse cross-section of  FIG. 13B . The cam  341  can be constructed of any suitable rigid material (e.g., plastic, polymer, metal, composite). In certain embodiments, the cam  341  is formed of Ultem®, a polyimide thermoplastic resin. 
       FIG. 13D  is an enlarged partial cross-section of the cam assembly  340 , showing the cam  341 , the cam spring  342 , and the cam dowel pin  343 .  FIG. 13D  also illustrates the interaction between the cam follower  324  disposed on the needle holder  321  and the contoured cam profile  346 . In certain embodiments, the cam spring  342  is a right hand torsion spring formed of stainless steel. In certain embodiments, the cam spring  342  can be formed of 7.5 coils of wire having a wire diameter of about 0.015 inches and an outer spring diameter of about 0.3 inches. One end of the cam spring  342  can be attached to the cam  341  and the other end can engage with engagement member  345  disposed on the right housing  304  (as shown in  FIG. 5A ). The cam spring  342  can be wound upon assembly and represents the stored energy that is transferred to the collet  322  to eject the implants  901 . 
     It should be appreciated by one of ordinary skill in the art, based on the disclosure herein, that the cam assembly  340  is one embodiment of a metering device configured to meter a variable amount of stored energy for the delivery of multiple implants at selected locations within eye tissue. The cam assembly  340  can be replaced with other suitable metering devices in other embodiments, such as a solenoid actuator. It should further be appreciated that the collet  322  can be replaced with other suitable driving members in other embodiments, such as a plunger, a stepper motor, or other device that can be mechanically or electrically activated to deliver energy (stored or not stored). 
     Assembly 
       FIGS. 14A and 14B  illustrate the assembly of the multiple-implant delivery apparatus  200  and show how all the internal components interact with each other upon placement within the right housing  304  during assembly. It should be appreciated that many methods of assembly can be used to assemble the multiple-implant delivery apparatus  200 . One embodiment of a method of assembly follows. 
     First, the sub-components of the various assemblies are assembled. The cam assembly  340  can be assembled by inserting the cam dowel pin  343  into the cam hub  345  and loading the cam spring  342  onto the right side of the cam  341 . The trigger button assembly  350  can be assembled by inserting the trigger dowel pin  353  into the trigger dowel pin slot  356  of the trigger button unit  351  and then attaching the trigger spring  352  to the trigger spring coupling member  356  of the trigger button unit  351 . The needle assembly  310  can be assembled by attaching (e.g., bonding) the needle  208  to the needle holder  312 . The trocar assembly  800  can be assembled by attaching (e.g., welding) the backup tube  816  to the trocar  814 . The collet holder assembly  320  can be assembled by attaching (e.g., bonding) the collet  322  to the collet holder  321  and then loading the collet return spring  323  over the collet  322 . 
     After assembling the individual subcomponents, the subcomponents are assembled together and placed within the right housing  304 . First, the ocular implants  901  can be loaded onto the trocar assembly  800  and the trocar assembly  800  can be loaded into the collet holder assembly  320 . The collet  322  can then be loaded within the insertion tube  903 , which in turn can be loaded into the needle assembly  310 . The cam assembly  340  can then be placed into the right housing  304  by inserting the right end of the cam dowel pin  343  into the right cam mount  344 B. Next, the trigger button assembly  350  can be attached to the right housing  304  by inserting the right end of the trigger dowel pin  353  into the right trigger mount  354 A. 
     After the cam assembly  340  and the trigger button assembly have been placed in the right housing  304 , the cam  341  can be wound and the trigger button unit  351  can be set. Then, the collet holder  341 , along with the attached needle assembly and trocar assembly, can be placed into the right housing  304  and the cam follower  324  can be aligned with the alignment mark  349  on the cam  341 . The collet return spring  323  can be set and the distal end of the collet  322  can be aligned with the distal end of the first of the implants  901  to be delivered. After the collet has been initially positioned, the trocar assembly  800  and the insertion tube  903  can be attached (e.g., bonded) to the right housing  304  using, for example, UV light adhesive bonding methods. 
     Next, the needle retraction link  335  and the needle retraction button unit  332  can be placed within the right housing  304 . The anchor  338  of the needle retraction button unit  332  can be inserted within the anchor slot  1138  of the needle retraction link  335  and the needle holder coupling member  1116  can be inserted within the link slot  316  of the needle holder  312 . The needle retraction spring  334  can then be attached to the needle retraction link  335  via the needle retraction spring slot  1134  and to the needle retraction spring mount  336 B of the right housing  304 . 
     Finally, the left housing  302  can be snapped onto the right housing  304  via snap-fit members  308  and the left and right fasteners  305  are inserted into their respective fastener slots  366 . 
     Operation of Multiple-Implant Delivery Apparatus 
       FIG. 15  illustrates the insertion of the multiple-implant delivery apparatus  200  within the eye  100  using an ab interno procedure. In one embodiment of implant delivery, the patient is placed in the supine position, prepped, draped and anesthesia obtained. In one embodiment, a small self-sealing (e.g., less than 1 mm) incision or opening is made in the cornea  112  at or near the limbus or in other external surface area of the eye. In certain embodiments, the needle  208  is inserted from a site transocularly situated from the desired implantation site. The needle  208  is then advanced through the corneal incision across the anterior chamber  120  toward the desired implantation site within the trabecular meshwork  121  under gonioscopic (lens) or endoscopic guidance. Although  FIG. 15  illustrates an ab interno method of insertion, it should be appreciated that ab externo methods of insertion are also contemplated. 
     Upon reaching the vicinity of the desired implantation site adjacent the trabecular meshwork  121 , the user presses the needle retraction button  214  and the needle  208  is retracted toward the external housing  202  and away from the implantation site, thereby exposing the trocar  814 , the collet  322 , and the insertion tube  903  and inhibiting the needle  208  from causing internal damage to the eye  100 . Manual depression of the needle retraction button  214  causes the needle retraction spring  334 , which is in tension, to compress and cause the needle retraction link  335  to be retracted toward the proximal end of the multiple-implant delivery apparatus  200 . The retraction of the needle retraction link  335  results in the retraction of the needle  208 , due to the coupling of the needle retraction link  335  with the needle holder  312 . The cutting tip  818  of the trocar  814  is then used to create an opening within the trabecular meshwork  121  at the desired implantation site. The cutting tip  818  of the trocar  818  is then advanced until it resides within Schlemm&#39;s canal or another physiologic outflow pathway. The advancement position can be determined by visualization (e.g., imaging or fiberoptic) or tactile methods or by depth markings or a depth stop. At this point, the first implant is ready to be delivered to the desired implantation site upon depression of the trigger button  316  by the user. 
       FIGS. 16A-16E  illustrate the functional operation between the cam  341  and the collet  322  in effecting delivery of the ocular implants  901 . As shown in  FIG. 16A , the cam follower  324  abuts against the surface of the contoured profile  346  of the cam  341 . As the cam  341  rotates in a clockwise manner, the variations in the contoured cam surface  346  cause the distal end of the collet  322  to move forward and backward along the longitudinal axis of the trocar  814 . The change in the radial length R as the cam  341  rotates, due to the variations in the cam contoured surface  346 , imparts linear axial motion to the collet  322  corresponding to the change in radial length. When R increases as the cam  341  rotates, the distal end of the collet  322  is driven toward the distal end of the trocar  814 . When R decreases as the cam  341  rotates, the distal end of the collet  322  is retracted within the insertion tube  903  and away from distal end of the trocar  814 . 
       FIG. 16A  illustrates twelve distinct points along the surface of the contoured profile  346  of the cam  341 . Each of the twelve points has an associated radial length that translates into a corresponding lateral position of the distal end of the collet  322 . The radial length at firing points C, F, I and L can advantageously be the same to ensure that the distal end of the collet  322  axially translates to the same travel endpoint position during delivery of each successive implant. However, the rising slope of peaks C, I and L can advantageously change to ensure that a substantially constant velocity is maintained during delivery of each successive implant. In sonic embodiments, the substantially constant velocity results in substantially the same implantation depth for each successive implant. 
       FIGS. 16B-16D  illustrate the delivery of a first implant  901 A at a first desired implantation site.  FIG. 16B  illustrates the initial starting position (point A) of the distal end of the collet  322  before the trigger button  216  is pressed for the first time by the user. As shown, the trocar  814  has been advanced through the trabecular meshwork  121  at the desired implantation site. In the illustrated embodiment, the implants  901  are arranged in tandem along the longitudinal axis of the trocar  814 . Each of the implants  901  includes an inner lumen through which at least a portion of the trocar  814  extends. The initial starting point of the distal end of the collet  322  corresponds with the front end of the first implant  901 A and can be spaced from the distal end of the trocar  814 . 
     Manual depression of the trigger button  216  releases the engagement between the trigger stop  359 B and the first cam flat  347 B, thereby allowing the cam  341  to freely rotate about the cam dowel pin  343  due to the spring force provided by the wound cam spring  342 . As the cam  341  rotates due to the unwinding of the cam spring  342 , the cam follower  324  of the collet holder  321  follows the contoured cam surface  346 , thereby causing the collet  322  to move laterally as a result of the change in the radius R. 
       FIG. 16C  illustrates the position of the distal end of the collet  322  after the trigger button  216  has been pressed by the user and the cam  341  has rotated to point B. As shown, the distal end of the collet  322  has been retracted (due to the slight decrease in the radial length of the cam  341  between point A and point B and due to the bias force provided by the collet return spring  323 ) to a position between the proximal end of the first implant  901 A and the distal end of a second implant  901 B. At point B, the collet  322  engages the proximal end of the first implant  901 A, effectively isolating, or “singulating,” the first implant  901 A for delivery. More specifically, as the collet return spring  323  biases the collet  322  away from the distal end of the trocar  814  due to the rotation of the cam  341  from point A to point B, the slots of the slotted sleeve  328  are caused to open and expand, thereby allowing the collet  322  to move over the first implant  901 A. 
       FIG. 16D  illustrates the position of the distal end of the collet  322  when the cam  341  has rotated to point C. The radius at point C is greater than the radius at point B, resulting in the axial translation of the collet  322  to the position depicted in  FIG. 16D . As shown, the first implant  901 A has been ejected from the trocar  814  due to the driving force of the collet  322  and now sits securely in the desired implantation site spanning the trabecular meshwork  121 . The travel distance of the distal end of the collet  322  is determined by the difference in radial length between points B and C and the delivery velocity is determined by the slope between point B and point C. The radial length at point C determines the travel end position of the collet  322  and the slope of the peak rising up to point C determines how fast the distal end of the collet  322  reaches the travel end position. 
       FIG. 16E  illustrates the position of the distal end of the collet  322  after the trigger button  216  has been released by the user and returned to its initial non-actuated state, due to the bias force provided by trigger spring  352 . At point D, the triangular cam flat receiving slot  359 A and the trigger stop  359 B have engaged the next cam flat  347 C, thereby inhibiting further rotation of the cam  341  until the trigger button  216  is pressed again by the user. As shown, the distal end of the collet  322  has been retracted backward (due to the decrease in radial length from point C to point D and due to the collet return spring  323 ) to a point corresponding to the distal end of the second implant  901 B. It should be appreciated that the distal position of the collet  322  at point D can be identical to the distal position of the collet  322  at point B, by configuring the radius R of the cam  341  to be substantially the same at points B and D. 
     As further shown in  FIG. 16E , the trocar  814  can be removed from the first implantation site in the internal eye tissue. The multiple-implant delivery apparatus  200  can then be moved to a second desired implantation site for delivery of the second implant  901 B within the same eye. Thus, the multiple-implant delivery apparatus  200  can advantageously deliver multiple ocular implants at multiple locations within the eye without necessitating removal of the needle  208  or trocar  814  from the eye to reload another implant. 
     The contoured cam surface  346 , in certain embodiments, is advantageously designed to deliver each of the implants  901  at a substantially constant delivery velocity to ensure repeatability and consistency in deployment (e.g., controlled extension distance or implantation depth) of the ocular implants between implantation sites within the same eye and within eyes of different patients. It should be appreciated by one of ordinary skill in the art, upon reading this disclosure, that in order to drive the collet  322  over a longer distance, more stored energy must be transmitted to the collet  322  by the cam spring  342 . The amount of energy transmitted is controlled by varying the slope of each of the four firing peaks (C, F, I and L) disposed on the contoured cam surface  346 . As best illustrated in  FIG. 16A , the length and steepness of the rising slope varies for each of the firing peaks in order to control the amount of energy transmitted by the cam spring  342  to the collet  322 . The change in slope also ensures that each successive implant is delivered with a substantially constant delivery velocity. The desired delivery velocity can be calculated to eject the implant at a velocity sufficient to position the implant so that the distal end of the implant resides within Schlemm&#39;s canal  122  (but not so far within Schlemm&#39;s canal  122  that the distal end of the implant comes in contact with the outer wall of Schlemm&#39;s canal  122 ) and so that the proximal end of the implant remains exposed to the anterior chamber  120  (as shown in  FIG. 18 ). For the embodiments of the multiple-implant delivery apparatus  200  and the implants  901  described herein, the ejection velocity required to obtain a successful implantation is from about 4,000 mm/sec to about 30,000 mm/sec, including about 9,000 mm/sec; to about 12,000 mm/sec and about 11,000 mm/sec. 
       FIG. 17  illustrates the position of the distal end of the collet  322  at each of the twelve points labeled in  FIG. 16A . As shown, because the implants are arranged serially in tandem, the distance required to be travelled by the collet  322  increases for each successive delivery cycle. For example, the distance travelled by the collet  322  as the cam  341  rotates from point E to point F to deliver the second implant  901 B is greater than the distance travelled by the collet  322  as the cam  341  rotates from point B to point C to deliver the first implant  901 A. As further shown, the travel end position of the distal end of the collet  322  can be the same at each of the four firing points C, F, I, and L by having the radial length of the cam  341  be substantially the same at each of the four firing points, In other embodiments, the radial length at each of the firing points can be different. 
     With continued reference to  FIG. 17 , the position of the distal end of the collet  322  is identical at the points on each side of the four firing peaks in order to ensure isolation, or singulation, of the next implant. This can be achieved by configuring the contoured cam surface  346  such that the radial length is substantially the same at the points immediately before and after delivery. For example, as shown, the position of the distal end of the collet  322  is the same at points B and D, E and G, and H and J. In other embodiments, the contoured cam surface  346  can be configured such that the collet  322  does not return to the point before the previous delivery (at the distal end of the next implant), but instead is retracted all the way back to the proximal end of the next implant. 
     In some embodiments, the multiple-implant delivery apparatus  200  can include a seal to prevent aqueous humor from passing through the multiple-implant delivery apparatus  200  and/or between the members of the multiple-implant delivery apparatus  200  when the instrument is in the eye. The seal can also aid in preventing backflow of aqueous humor through the multiple-implant delivery apparatus  200  and out the eye, Suitable seals for inhibiting leakage include, for example, an O-ring, a coating, a hydrophilic agent, a hydrophobic agent, and combinations thereof. The coating can be, for example, a silicone coat such as MDX™ silicone fluid. In some embodiments, the multiple-implant delivery apparatus  200  is coated with the coating and a hydrophilic or hydrophobic agent. In some embodiments, one region of the apparatus is coated with the coating plus the hydrophilic agent, and another region of the apparatus is coated with the coating plus the hydrophobic agent. The seal can comprise a hydrophobic or hydrophilic coating between slip-fit surfaces of the members of the apparatus. The seal can be disposed proximate of an implant when carried by the multiple-implant delivery apparatus  200  In accordance with several embodiments, the seal is advantageously present on at least a section of each of two devices that are machined to fit closely with one another. In various embodiments, the seal is present on at least an inner surface of the insertion tube  1902 , an outer surface of the collet  322 , or both. 
     Although the operation of the multiple-implant delivery apparatus  200  has been described in conjunction with a cam as the metering device and a collet as the driving member, it should be appreciated that other suitable metering devices and driving members can be used to accomplish the delivery of multiple implants at a constant velocity. In addition, although the operation of the multiple-implant delivery apparatus  200  has been described in conjunction with a wound cam torsion spring providing the stored energy that is transmitted to the collet, it should be appreciated that other suitable stored energy sources can be used to transmit energy to a driving member (e.g., relaxation of a non-torsion spring such as a compression spring). 
     Implants 
     As used herein, “implants” refers to ocular implants which can be implanted into any number of locations in the eye. In some embodiments, the ocular implants are drainage implants designed to facilitate or provide for the drainage of aqueous humor from the anterior chamber of an eye into a physiologic outflow pathway in order to reduce intraocular pressure. In some embodiments, the implant can be sized and shaped to provide a fluid flow path for draining aqueous humor from the anterior chamber through the trabecular meshwork and into Schlemm&#39;s canal. In other embodiments, the implant can be configured to provide a fluid flow path for draining aqueous humor from the anterior chamber to a uveoscleral outflow pathway. In some embodiments, the aqueous humor is diverted to the supraciliary space or the suprachoroidal space of the uveoscleral outflow pathway. 
     The term “implant” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to drainage shunts, stents, sensors, drug delivery implants, drugs, therapeutic agents, fluids, or any other device or substance capable of being inserted within an eye. 
     In certain embodiments, one or more of the implants are ocular implants for purposes other than drainage (for example, a drug delivery device or an ocular sensor for measuring intraocular pressure or components of ocular fluid, such as glucose). In some embodiments, an implant comprises two sections or portions tethered together, such as a sensor tethered to a drainage implant, a sensor tethered to an anchor. 
     In some embodiments, drainage implants define one or more fluid passages. The fluid passages) in some embodiments remains patent and, in other embodiments, the passage(s) is fully or partially occluded under at least some circumstances (e.g., at lower intraocular pressure levels). The implants may feature a variety of characteristics, described in more detail below, which facilitate the regulation of intraocular pressure. The mechanical aspects and material composition of the implant can be important for controlling the amount and direction of fluid flow. Therefore, various examples of implant dimensions, features, tip configurations, material flexibility, coatings, and valve design, in accordance with some embodiments of the present disclosure, are discussed in detail below. While ocular implants will he described herein, it should he appreciated that other types of implants can be used by embodiments of the systems and methods described herein for implantation into other body tissue or body cavities. The term “implant” can he interchanged with the words “stent” or “shunt” in various embodiments. 
       FIG. 18  is an enlarged schematic and partial sectional view of Schlemm&#39;s canal  122  and the trabecular meshwork  121  of the eye  100  illustrating the implantation position and the operation of one type of implant  901  that may be delivered by the multiple-implant delivery apparatus  200 . As shown, the implant  901  is delivered such that the proximal end  902 A is positioned within the anterior chamber  120  and the distal end  902 B of the implant is positioned within Schlemm&#39;s canal  122 . Accordingly, the multiple-implant delivery apparatus  200  can be configured to deliver the implant  901  so that the distal end  902 B penetrates through the trabecular meshwork and the inner wall  912  of Schlemm&#39;s canal  122  without penetrating through the outer wall  914  of Schlemm&#39;s canal  122 . 
     The implant  901  is a substantially axisymmetric implant. The implant  901  can be divided for description purposes into a proximal portion  904 , an intermediate portion  905 , and a distal portion  907 . The lumen  908  can extend from a proximal end  902 A through each of the portions to a distal end  902 B of the implant  901  and is configured to provide fluid communication between the proximal and distal ends. The lumen  908  defines an axis upon which the three portions of the implant  901  are serially aligned. 
     The proximal portion  904  is generally cylindrical with the lumen extending therethrough. The proximal end  902 A of the implant  901  can comprise a generally flat surface that defines an opening in the middle thereof to provide fluid communication between the exterior of the proximal portion  904  and the lumen  908 . The exterior surfaces of the proximal portion  904  can be generally smooth, and the edge between the proximal end  902 A and the sides of the proximal portion  904  can be generally rounded, beveled or sharpened. In embodiments where the edge between the proximal end  902 A and the sides of the proximal portion  904  is sharpened, the sharpened edge may prevent or reduce the likelihood of fibrosis from growing up and over the edge and into the inlet, thereby clogging flow. The proximal portion  904  can have a cross-sectional measurement (e.g., a diameter) of between about 0.01 mm and about 0.5 mm (0.2 mm, for example), and the opening can have a cross-sectional measurement of about 0.001 mm to about 0.4 mm (0.08 mm, for example). The implant  901  can be between about 0.01 and 1 mm long (0.3 mm, for example) from the proximal end  902 A to its distal end  902 B. 
     The intermediate portion  905  can also be generally cylindrical, aligned along the same axis as the proximal portion  904 , and can have a reduced cross-sectional measurement relative to the proximal portion  904 . Accordingly, the intermediate portion  905  can have a cross-sectional measurement ranging between about 0.001 mm to about 0.4 mm (0.1 to 0.18 mm, for example). The lumen  908  extends through the intermediate portion  905  along the same axis as through the proximal portion  904  and has a cross-sectional measurement of between about 0.001 mm to about 0.4 mm (0.08 mm, for example). The exterior surfaces of the intermediate portion  905  can be generally smooth, and the portion&#39;s junctions with the proximal portion  904  and the distal portion  907  can be generally rounded, chamfered, beveled sharpened, or have a substantially defined edge. In other embodiments, the intermediate portion  905  and the proximal portion  904  can have the same cross-sectional dimension such that the two portions essentially form a single portion. 
     The distal portion  907  of the implant  901  can also be generally aligned along the same axis as the proximal portion  904  and the intermediate portion  905  and can have a generally frustoconical exterior configuration. The proximal end of the distal portion  907  can comprise a flat annular surface that extends from the junction of the intermediate portion  905  at about ninety degrees and extends to the edges of the proximal end. The cross-sectional measurement at the proximal end of the distal portion  907  can be about 0.05 to about 0.5 mm (about 0.2 mm, for example). The sides of the distal portion  907  extend distal of its proximal end in a tapered configuration, similar to that of a cone. The sides of the distal portion  907  are tapered until the sides terminate at the distal end upon meeting the lumen that extends through the implant  901 , thus forming a frustoconical shape having a flat distal end. The sides of the distal portion  907  can include openings or apertures (e.g., outlet ports  906 ) positioned circumferentially along the frustoconical distal portion  907  that provide fluid communication between the exterior of the distal portion  907  and the lumen  908  extending through the implant  901 . The surface of the distal end of the distal portion  907  can include an outlet or aperture that is axially aligned with the lumen of the distal portion  907  (not shown). The lumen that extends through the distal portion  907  of the implant  901  is preferably axially aligned with the lumen extending through both the proximal and intermediate portions. 
     Referring to  FIG. 18 , the aqueous humor flows from the anterior chamber  120 , through the inlet lumen  908 , and then out through one, two or more of four side outlet ports ( 906 A,  906 B,  906 C and a fourth outlet port opposite outlet port  906 C) to be directed in both directions along Schlemm&#39;s canal  122 . In some embodiments, the implant  901  includes an axial outlet port in communication with the inlet lumen  908  that is located along a distal end  902 B to potentially direct flow in an axial direction if the distal end  902 B is not obstructed. Alternatively, flow could be directed in only one direction through a single outlet port  906 A or flow could be directed in two directions through two outlet ports  906 A and  906 B, depending on a rotational position of the implant  901  within Schlemm&#39;s canal or other physiologic outflow pathway upon implantation. In other embodiments, more than two outlet ports  906  can be efficaciously used, as needed or desired to increase outflow or reduce the potential for obstruction of the outlet ports to flow within Schlemm&#39;s canal  122 . For example, in some embodiments, four outlet ports  906 A,  906 B,  906 C and a fourth outlet port opposite outlet port  906 C can be oriented at 90 degrees with respect to the inlet lumen  908  and with respect to adjacent outlet ports such that an outlet port is positioned at every 90 degree rotation of the implant  901 . The use of four or more outlet ports may increase the likelihood that at least two outlet ports are oriented to facilitate flow within Schlemm&#39;s canal  122  without rotational adjustment or orientation after delivery or implantation. The proximal end of the distal portion  907  can abut the inner wall  912  of Schlemm&#39;s canal  122 , and the distal end of the proximal portion  904  can abut the trabecular meshwork  121  upon delivery. Accordingly, the implant  901  can be secured in place by the proximal and distal portions of the implant  901  abutting opposite sides of the trabecular meshwork  121 . In some embodiments, the distal end  902 B is in contact with the outer wall  914  of Schlemm&#39;s canal  122 . In some embodiments, an additional axial outlet is located at the distal end  902 B. In such embodiments, the main lumen  908  may also be in fluid communication with this additional axial outlet. In some instances, the axial outlet is non-functional because it is in contact with a wall of Schlemm&#39;s canal when implanted, and therefore outflow through the axial outlet is blocked. In alternative embodiments, the implant  901  can be implanted such that an outlet of the implant  901  is positioned in a physiologic outflow pathway other than Schlemm&#39;s canal  122 . 
     At least some of the disclosed embodiments include implants that provide a fluid flow path for conducting aqueous humor from the anterior chamber of an eye to a physiologic outflow pathway to reduce intraocular pressure, preferably below episcleral venous pressure without hypotony. The implants can have an inflow portion and an outflow portion. The outflow portion of the implant preferably is disposed at or near a distal end of the implant. When the implant is implanted, the inflow portion may be sized and configured to reside in the anterior chamber of the eye and the outflow portion may be sized and configured to reside in a physiologic outflow pathway. In some embodiments, the outflow portion may be sized and configured to reside in Schlemm&#39;s canal. In other embodiments, the outflow portion may be sized and configured to reside at least partially in the supraciliary region of the uveoscleral outflow pathway or the suprachoroidal space. 
     One or more lumens can extend through the implant to form at least a portion of the flow path. In some embodiments, there is at least one lumen that operates to conduct the fluid through the implant. Each lumen preferably extends from an inflow end to an outflow end along a lumen axis. In some embodiments the lumen extends substantially through the longitudinal center of the implant. In other embodiments, the lumen can be offset from the longitudinal center of the implant. In still other embodiments, the flow path can be defined by grooves, channel or reliefs formed on an outer surface of the implant body. 
     One or more openings can extend through the wall of the implant. In some embodiments, the openings can extend through a middle portion of the implant. In other embodiments the openings can extend through other portions of the implant. The openings can be one or more of a variety of functions. One such function is that when the implant is inserted into the physiologic outflow pathway, the openings provide a plurality of routes through which the aqueous humor can drain. For example, once the implant is inserted into the eye, if the implant only has one outflow channel (e.g., one end of a lumen), that outflow channel can be plugged, for example, by the implant&#39;s abutment against the outer wall of Schlemm&#39;s canal or against the interior surface of the sclera or the outer surface of the choroid. Additionally, the outflow channel can be clogged with tissue that is accumulated or cored during the advancement of the implant through the fibrous or porous tissue. A plurality of openings can provide a plurality of routes through which the fluid may flow to maintain patency and operability of the drainage implant. In embodiments where the implant has a porous body, the openings can define surface discontinuities to assist in anchoring the implant once implanted. 
     The implant in some embodiments can include a distal portion that is sufficiently sharp to pierce eye tissue, including eye tissue in the trabecular meshwork or eye tissue near the scleral spur of the eye, and that is disposed closer to the outlet portion than to the inlet portion. In some embodiments, the distal portion is located at the distal end of the implant. In another embodiment, the distal portion can be sufficiently blunt so as not to substantially penetrate eye tissue. In some embodiments, the implants have a generally sharpened forward end and are self-trephinating, i.e., self-penetrating, so as to pass through tissue without pre-forming an incision, hole or aperture. The sharpened forward end can be, for example, conical or tapered. The tip can be sufficiently sharp to pierce eye tissue. The tip also can be sufficiently blunt so as not to substantially penetrate eye tissue. The taper angle of the sharpened end can be, for example, about 30°±15° in some embodiments. The radius of the tip can be about 70 to about 200 microns. In other embodiments, where an outlet opening is formed at the distal end of the implant, the distal portion can gradually increase in cross-sectional size in the proximal direction, preferably at a generally constant taper or radius or in a parabolic manner. In some embodiments including an outlet opening at the distal end, the diameter of the axial outlet opening formed at the distal end may be between 40 and 200 microns (e.g., 40 microns, 60 microns, 80 microns, 100 microns, 120 microns, 120 microns, 140 microns, 160 microns, 180 microns). Additionally, in such embodiments, an annulus may be formed between an edge defined by the outer circumference of the axial outlet opening and an edge defined by the intersection of the distal tip surface and the conical or tapered section of the distal portion. The width of this annulus may advantageously be sufficiently small such that, after the trocar has created a pilot hole in eye tissue (e.g., trabecular meshwork), the distal portion can expand eye tissue surrounding the pilot hole as the implant is advanced into the eye tissue. The eye tissue can then retract around an intermediate portion of the eye implant. If the annulus width is not sufficiently small, the distal portion may potentially push, rather than expand, the eye tissue. 
     In some embodiments, the body of the implant can include at least one surface irregularity. The surface irregularity can include, for example, a ridge, groove, relief, hole, or annular groove. The surface discontinuities or irregularities can also be formed by barbs or other projections, which extend from the outer surface of the implant, to inhibit migration of the implant from its implanted position. In some embodiments, the projections can include external ribbing to resist displacement of the implant. The surface irregularity in some embodiments can interact with the tissue of the trabecular meshwork or with the interior wall of the sclera and/or with the tissue of the ciliary attachment tissue in order to provide an anchoring function. In some embodiments, the implants are anchored by mechanical interlock between tissue and an irregular surface and/or by friction fit. In other embodiments, the implant includes cylindrical recessed portions (e.g., annular groves) along an elongate body to provide enhanced gripping features during implantation and anchoring following implantation within the eye tissue. 
     The implant can also incorporate fixation features, such as flexible radial (i.e., outwardly extending) extensions. The extensions may be separate pieces attached to the implant, or may be formed by any suitable method, including slitting the implant wall, and thermally forming or mechanically deforming the extensions radially outward. If the extensions are separate pieces, they can be composed of flexible material such as nitinol or polyimide. The extensions may be located at the proximal or distal ends of the implant, or both, to prevent or resist extrusion of the implant from its intended location. The flexibility of the fixation features will facilitate entry through the corneal incision, and also through the eye tissue. 
     The implant can also comprise a body structure having one or more surfaces having a plurality of nanostructured components associated therewith. The plurality of nanostructured components can include, for example, carbon nanotubes, nanofibers, nanowires, or nanofibrous mesh. The plurality of nanostructured components enhance one or more of adhesion, non-adhesion, friction, patency or biointegration of the implant with one or more tissue surfaces of a body of a patient. In certain embodiments, the nanostructured components on the surfaces of the implant can be embedded in a biocompatible matrix to hold the nanostructured components together. 
     In some embodiments, the body of the implant has an outlet opening on a side surface to allow fluid flow. In some embodiments, the body of the implant has a plurality of outlet openings on a side surface to allow fluid flow. In other embodiments, there is a plurality of outlet openings at one end of the implant, such as the distal end. The openings can facilitate fluid flow through the implant. 
     The implant can in some embodiments have a cap, or tip, at one end. The cap can include a tissue-piercing end and one or more outlet openings. Each of the one or more outlet openings can communicate with at least one of the one or more lumens. In some embodiments, the cap can have a conically shaped tip with a plurality of outlet openings disposed proximal of the tip&#39;s distal end. In other embodiments, the cap can have a tapered angle tip. The tip can be sufficiently sharp to pierce eye tissue. The tip also can be sufficiently blunt so as not to substantially penetrate eye tissue in the absence of sufficient force. In some embodiments, the conically shaped tip facilitates delivery of the implant to the desired location. In some embodiments, the cap has an outlet opening on a side surface to allow fluid flow. In some embodiments, the cap has a plurality of outlet openings on a side surface to allow fluid flow. In other embodiments, there is a plurality of outlet openings on the conical surface of the cap. The openings on the cap can facilitate fluid flow through the implant. The opening may provide an alternate route for fluid flow which is beneficial in case the primary outflow portion of the implant becomes blocked. 
     In some embodiments, multiple implants are configured to be delivered during a single procedure. In some embodiments when multiple implants are delivered, the implants can be arranged in tandem. In one embodiment, the implant can include a tip protector at one end. The tip protector can include a recess shaped to receive and protect, for example, the tip of an adjacent implant. In some embodiments, the tip of the adjacent implant has a conical shape. The recess may be shaped to contact the sides of the conical tip while protecting the more tapered tip, or end, from impact. The tip protector is particularly useful for delivery of multiple implants. 
     The implants may be of varied lengths and sizes to optimize flows. In some embodiments, the implant has sufficient length such that the outflow portion resides in a physiologic outflow pathway and the inflow portion is exposed to the anterior chamber. In sonic embodiments, the length of the implant from the portion residing in the anterior chamber to the portion residing in the physiologic outflow pathway may be about 0.001 mm to about 5 mm, about 0.01 mm to about 1 mm, about 0.1 mm to about 0.5 mm, or overlapping ranges thereof. In some embodiments, the length of the implant is about 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, 0.45, or 0.50 mm. 
     In some embodiments, the implant can have an outer diameter that will permit the implant to fit within a 23-gauge needle during implantation. The implant can also have a diameter that is designed to be inserted with larger needles. For example, the implant can also be delivered with 18-, 19- or 20-gauge needles. In other embodiments, smaller gauge applicators, such as a 25-gauge (or smaller) applicator, may be used. The implant can have a substantially constant cross-sectional shape through most of the length of the implant, or the implant can have portions of reduced or enlarged cross-sectional size (e.g., diameter), or cylindrical channels, e.g., annular grooves, disposed on the outer surface between the proximal end and the distal end. The distal end of the implant can have a tapered portion, or a portion having a continually decreasing radial dimension with respect to the lumen axis along the length of the axis. The tapered portion preferably in some embodiments terminates with a smaller radial dimension at the outflow end. During implantation, the tapered portion can operate to form, dilate, and/or increase the size of, an incision or puncture created in the tissue. The tapered portion may have a diameter of about 23 gauge to about 30 gauge, and preferably about 25 gauge. However, other dimensions are possible. 
     The diameter of one or more drainage lumens within the implant may be varied to alter flow characteristics. The cross-sectional size of an implant may be, for example, from about 0.1 mm to about 1.0 mm (for example, from about 0.3 mm to about 0.4 mm). A small cross-sectional size can be used to restrict flow. The cross-sectional shape of the implant or an implant may be any of a variety of cross-sectional shapes suitable for allowing fluid flow. For example, the cross-sectional shape of the implant or implant may be circular, oval, square, trapezoidal, rectangular, or any combination thereof. 
     In some embodiments, the implant is configured to expand, either radially or axially, or both radially and axially. In some embodiments, the implant may be self-expanding. In other embodiments, the implant may be expanded by, for example, using a balloon device. 
     In some embodiments, the structure of the implant may be flexible. At least a portion of the structure of the implant may be flexible, or the whole structure may be flexible. In some embodiments, the structure of the implant is accordion- or balloon-like. This pleated like structure provides flexibility. In other embodiments, at least a portion of the implant is curved. In some embodiments, at least a portion of the implant is straight. In some embodiments, the implant has both curved and straight portions, and in some embodiments, the implant is generally rigid (i.e., maintains its preformed shape when implanted). 
     The implant is preferably made of one or more biocompatible materials. Suitable biocompatible materials include, for example, polypropylene, polyimide, glass, nitinol, polyvinyl alcohol, polyvinyl pyrolidone, collagen, chemically-treated collagen, polyethersulfone (PES), polystyrene-isobutyl-styrene), Pebax, acrylic, polyolefin, polysilicon, polypropylene, hydroxyapetite, titanium, gold, silver, platinum, other metals, ceramics, plastics and a mixture thereof. The implants can be manufactured by sintering, micro machining, laser machining, and/or electrical discharge machining. However, other suitable manufacturing methods can be used. 
     In some embodiments, the implant is made of a flexible material. In other embodiments, the implant is made of a rigid material, In some embodiments, a portion of the implant is made from flexible material while another portion of the implant is made from rigid material. The body can have an outer surface of which at least a portion is porous. Some embodiments include porosity that can be varied by masking a portion of the exterior with a band. Where the implants include a porous body, the cross-section and porosity can be calibrated (down to 0.5 micrometers) to control the flow rates of aqueous humor through the implant. 
     In some embodiments, at least a portion of the implant (e.g., an internal spine or an anchor) is made of a material capable of shape memory. A material capable of shape memory may be compressed and, upon release, may expand axially or radially, or both axially and radially, to assume a particular shape. In some embodiments, at least a portion of the implant has a preformed shape. In other embodiments, at least a portion of the implant is made of a superelastic material. In some embodiments, at least a portion of the implant is made up of Nitinol. In other embodiments, at least a portion of the implant is made of a deformable material. 
     In some embodiments, the body of the implant can be formed of material that includes a therapeutic agent, and/or can house, anchor, or support a therapeutic agent, or can include a coating. The coating can include a therapeutic agent. The coatings can be, for example, a drug eluting coating, an antithrombogenic coating, and a lubricious coating. The therapeutic agent can be selected from the group consisting of: heparin, TGF-beta, an anti-glaucoma or intraocular pressure-lowering drug, anti-inflammatory agents, antibiotics, pharmaceutical agents, biological agents including hormones, enzyme or antibody-related components, oligonucleotides, DNA/RNA vectors and live cells configured to produce one or more biological components, an anti-proliferative agent, and a vasodilator. Materials that may be used for a drug-eluting coating include parylene C, poly (butyl methacrylate), poly (methyl methacrylate), polyethylene-co-vinyl acetate, and other materials. 
     In some embodiments, the implant can further include a biodegradable material in or on the implant. The biodegradable material can be selected from the group consisting of polylactic acid), polyethylene-vinyl acetate, polylactic-co-glycolic acid), poly(D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate), collagen, heparinized collagen, poly(caprolactone), poly(glycolic acid), and a copolymer. All or a portion of the implant may be coated with a therapeutic agent, e.g. with heparin, preferably in the flow path, to reduce blood thrombosis or tissue restenosis. 
     The flow path through the implant can be configured to be regulated to a flow rate that will reduce the likelihood of hypotony in the eye. In some embodiments, the intraocular pressure is maintained at about 8 mm Hg. In other embodiments, the intraocular pressure is maintained at pressures less than about 8 mmHg, for example the intraocular pressure may be maintained between about 6 mm Hg and about 8 mm Hg. In other embodiments, the intraocular pressure is maintained at pressures greater than about 8 mm Hg. For example, the pressures may be maintained between about 8 mmHg and about 18 mm Hg, and more preferably between 8 mm Hg and 16 mm Hg, and most preferably not greater than 12 mm Hg. In some embodiments, the flow rate can be limited to about 2.5 μL/min or less. In some embodiments the flow rate can be limited to between about 1.9 μL/min and about 3.1 μL/min. 
     For example, the Hagen-Poiseuille equation suggests that a 4 mm long stent at a flow rate of 2.5 μL/min should have an inner diameter of 52 microns to create a pressure gradient of 5 mm Hg above the pressure in the suprachoroidal space. 
     The implant may or may not include a mechanism for regulating fluid flow through the implant. Mechanisms for regulating fluid flow can include flow restrictors, pressure regulators, or both. Alternatively, in some embodiments the implant has neither a flow restrictor nor a pressure regulator. Regulating flow of aqueous humor can include varying between at least first and second operational states in which aqueous humor flow is more restricted in a first state and less restricted in a second state. Increasing the restriction to flow when changing from the second state to the first state can involve moving a valve toward a valve seat in a direction generally parallel or generally normal to a line connecting the proximal and distal ends of the implant. 
     As noted above, the outflow portion of the implant, in some embodiments is sized and configured to reside in the Schlemm&#39;s canal. In such embodiments, there is a lesser need for a mechanism for regulating fluid flow through the implant. The mechanism for flow restriction may be, for example, a valve, a long lumen length, small lumen cross section, or any combination thereof. In some embodiments, the flow of fluid is restricted by the size of a lumen within the implant, which produces a capillary effect that limits the fluid flow for given pressures. The capillary effect of the lumen allows the implant to restrict flow and provides a valveless regulation of fluid flow. 
     In one embodiment, the flow path length may be increased without increasing the overall length of the implant by creating a lumen with a spiral flow path. A lumen within the implant is configured to accommodate placement therein of a spiral flow channel core that is configured to provide flow restriction. In effect, the spiral flow channel provides an extended path for the flow of fluid between the inlet(s) and outlet(s) of the implant that is greater than a straight lumen extending between the ends of the implant. The extended path provides a greater potential resistance of fluid flow through the implant without increasing the length of the implant. The core could have a single spiral flow channel, or a plurality of spiral flow channels for providing a plurality of flow paths through which fluid may flow through the implant. For example, the core can have two or more spiral flow channels, which can intersect. 
     In some embodiments, the mechanism for flow regulation can include a pressure regulating valve. In one embodiment, the valve can open when fluid pressure within the anterior chamber exceeds a predetermined level (e.g., a preset pressure). Intraocular pressure may be used to apply a force to move a valve surface within the implant in a direction transverse to a longitudinal axis of the implant such that aqueous humor flows from the anterior chamber to an outflow pathway at intraocular pressures greater than a threshold pressure. 
     In some embodiments, the implant may have any number of valves to restrict flow and/or regulate pressure. The valve can be located between the anterior chamber and one or more effluent openings such that movement of the valve regulates flow from the anterior chamber to the one or more effluent openings. A variety of valves are useful with the implant for restricting flow. In some embodiments, the valve is a unidirectional valve and/or is a pressure relief valve. The pressure relief valve can include a ball, a ball seat and a biasing member urging the ball towards the ball seat. In some embodiments, the valve is a reed-type valve. In a reed valve, for example, one end of the valve may be fixed to a portion of the implant. The body of the reed valve can be deflected in order to allow flow through the valve. Pressure from fluid in the anterior chamber can deflect the body of the reed valve, thereby causing the valve to open. 
     In some embodiments, the implant can include a pressure regulation valve having a deflectable plate or diaphragm with a surface area exposed to fluid within the anterior chamber, the surface area being substantially greater than the total cross-sectional flow area of the one or more influent openings of the implant. Such a valve can be disposed between an anterior chamber of the implant and the one or more effluent openings such that movement of the deflectable plate regulates flow from the anterior chamber to the one or more effluent openings. The plate can extend in a direction generally parallel to the inlet flow path and to the outlet flow path. 
     When the intraocular pressure exceeds a predetermined pressure, the check pressure relief valve can open and permit fluid to flow between the anterior chamber and the physiologic outflow pathway. When the intraocular pressure decreases to a second, lower pressure, the valve can close to limit or inhibit fluid from flowing to the physiologic outflow pathway. In one embodiment, the valve can remain closed until the intraocular pressure again reaches the predetermined pressure, at which time the valve can reopen to permit or enhance drainage of fluid to the physiologic outflow pathway. Accordingly, the implant can provide drainage of the anterior chamber through the implant based on the intraocular pressure levels and reduce the likelihood for over-draining the anterior chamber and causing hypotony. 
     In some embodiments, the implant can provide for delivery of a therapeutic agent or drug. The therapeutic agent can be, for example, an intraocular pressure-lowering drug. In some embodiments, the therapeutic agent or drug is introduced concurrently with the delivery of the shunt to the eye. The therapeutic agent or drug can be part of the implant itself. For example, the therapeutic agent or drug can be embedded in the material of the shunt, or coat at least a portion of the implant. The therapeutic agent or drug may be present on various portions of the implant. For example, the therapeutic agent or drug may be present on the distal end of the implant, or the proximal end of the implant. The implant can include combination of therapeutic agents or drugs. The different therapeutic agents or drugs can be separated or combined. One kind of therapeutic agent or drug can be present at the proximal end of the implant, and a different kind of therapeutic agent or drug can be present at the distal end of the implant. For example, an anti-proliferative agent may be present at the distal end of the implant to prevent growth, and a growth-promoting agent may be applied to the proximal end of the implant to promote growth. 
     In some embodiments, the implant includes a chamber or reservoir at least partially filled with a solid or liquid drug or therapeutic agent that can be eluted over time. The drug or therapeutic agent can be located within a lumen of the implant. The release of the drug or therapeutic agent can be controlled by a membrane (which can be porous or non-porous). 
     Examples of drugs may include various anti-secretory agents; antimitotics and other anti-proliferative agents, including among others, anti-angiogenesis agents such as angiostatin, anecortave acetate, thrombospondin, VEGF receptor tyrosine kinase inhibitors and anti-vascular endothelial growth factor (anti-VEGF) drugs such as ranibizumab (LUCENTIS®) and bevacizurnab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib and sorafenib and any of a variety of known small-molecule and transcription inhibitors having anti-angiogenesis effect (additional non-limiting examples of such anti-VEGF compounds are described in Appendix A, which is attached herewith and made a part of this application); classes of known ophthalmic drugs, including: glaucoma agents, such as adrenergic antagonists, including for example, beta-blocker agents such as atenolol, propranolol, metipranolol, betaxolol, carteolol, levobetaxolol, levobunolol and timolol; adrenergic agonists or sympathomimetic agents such as epinephrine, dipivefrin, clonidine, aparclonidine, and brimonidine; parasympathomimetics or cholingeric agonists such as pilocarpine, carbachol, phospholine iodine, and physostigmine, salicylate, acetylcholine chloride, eserine, diisopropyl fluorophosphate, demecarium bromide); muscarinics; carbonic anhydrase inhibitor agents, including topical and/or systemic agents, for example acetozolamide, brinzolamide, dorzolamide and methazolamide, ethoxzolamide, diamox, and dichlorphenamide; mydriatic-cycloplegic agents such as atropine, cyclopentolate, succinylcholine, homatropine, phenylephrine, scopolamine and tropicamide; prostaglandins such as prostaglandin F2 alpha, antiprostaglandins, prostaglandin precursors, or prostaglandin analog agents such as birnatoprost, latanoprost, travoprost and unoprostone. 
     Other examples of drugs may also include anti-inflammatory agents including for example glucocorticoids and corticosteroids such as betamethasone, cortisone, dexamethasone, dexamethasone 21-phosphate, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, prednisolone, fluorometholone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, beclomethasone, budesonide, flunisolide, fluticasone, hydrocortisone, hydrocortisone acetate, loteprednol, rimexolone and non-steroidal anti-inflammatory agents including, for example, diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, and ketorolac, salicylate, indomethacin, ibuprofen, naxopren, piroxicam and nabumetone; anti-infective or antimicrobial agents such as antibiotics including, for example, tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodium propionate, aminoglycosides such as gentamicin and tobramycin; fluoroquinolones such as ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin; bacitracin, erythromycin, fusidic acid, neomycin, polymyxin B, gramicidin, trimethoprim and sulfacetamide; antifungals such as amphotericin B and miconazole; antivirals such as idoxuridine trifluorothymidine, acyclovir, gancyclovir, interferon; antimicotics; immune-modulating agents such as antiallergenics, including, for example, sodium chromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine, pyrilamine, prophenpyridamine; anti-histamine agents such as azelastine, emedastine and levocabastine; immunological drugs (such as vaccines and immune stimulants); MAST cell stabilizer agents such as cromolyn sodium, ketotifen, lodoxamide, nedocrimil, olopatadine and pemirolastciliary body ablative agents, such as gentimicin and cidofovir; and other ophthalmic agents such as verteporfin, proparacaine, tetracaine, cyclosporine and pilocarpine; inhibitors of cell-surface glycoprotein receptors; decongestants such as phenylephrine, naphazoline, tetrahydrazoline; lipids or hypotensive lipids; dopaminergic agonists and/or antagonists such as quinpirole, fenoldopam, and ibopamine; vasospasm inhibitors; vasodilators; antihypertensive agents; angiotensin converting enzyme (ACE) inhibitors; angiotensin-1 receptor antagonists such as olmesartan; microtubule inhibitors; molecular motor (dynein and/or kinesin) inhibitors; actin cytoskeleton regulatory agents such as cyctchalasin, latrunculin, swinholide A, ethacrynic acid, H-7, and Rho-kinase (ROCK) inhibitors; remodeling inhibitors; modulators of the extracellular matrix such as tert-butylhydro-quinolone and AL-3037A; adenosine receptor agonists and/or antagonists such as N-6-cylclophexyladenosine and (R)-phenylisopropyladenosine; serotonin agonists; hormonal agents such as estrogens, estradiol, progestational hormones, progesterone, insulin calcitonin, parathyroid hormone, peptide and vasopressin hypothalamus releasing factor; growth factor antagonists or growth factors, including, for example, epidermal growth factor, fibroblast growth factor, platelet derived growth factor or antagonists thereof (such as those disclosed in U.S. Pat. No. 7,759,472 or U.S. patent application Ser. Nos. 12/465,051, 12/564,863, or 12/641,270, each of which is incorporated in its entirety by reference herein), transforming growth factor beta, somatotrapin, fibronectin, connective tissue growth factor, bone morphogenic proteins (BMPs); cytokines such as interleukins, CD44, cochlin, and serum amyloids, such as serum amyloid A. 
     Other therapeutic agents may include neuroprotective agents such as lubezole, nimodipine and related compounds, and including blood flow enhancers such as dorzolamide or betaxolol; compounds that promote blood oxygenation such as erythropoeitin; sodium channels blockers; calcium channel blockers such as nilvadipine or lomerizine; glutamate inhibitors such as memantine nitromemantine, riluzole, dextromethorphan or agmatine; acetylcholinsterase inhibitors such as galantamine; hydroxylamines or derivatives thereof, such as the water soluble hydroxylamine derivative OT-440; synaptic modulators such as hydrogen sulfide compounds containing flavonoid glycosides and/or terpenoids, such as ginkgo biloba; neurotrophic factors such as glial cell-line derived neutrophic factor, brain derived neurotrophic factor; cytokines of the IL-6 family of proteins such as ciliary neurotrophic tactor or leukemia inhibitory factor; compounds or factors that affect nitric oxide levels, such as nitric oxide, nitroglycerin, or nitric oxide synthase inhibitors, cannabinoid receptor agonsists such as WIN55-212-2; free radical scavengers such as methoxypolyethylene glycol thioester (MPDTE) or methoxypolyethlene glycol thiol coupled with EDTA methyl triester (MPSEDE); anti-oxidants such as astaxathin, dithiolethione, vitamin E, or metallocorroles (e.g., iron, manganese or gallium corroles); compounds or factors involved in oxygen homeostasis such as neuroglobin or cytoglobin; inhibitors or factors that impact mitochondrial division or fission, such as Mdivi-1 (a selective inhibitor of dynamin related protein 1 (Drp1)); kinase inhibitors or modulators such as the Rho-kinase inhibitor H-1152 or the tyrosine kinase inhibitor AG1478; compounds or factors that affect integrin function, such as the Beta 1-integrin activating antibody HUTS-21; N-acyl-ethanaolamines and their precursors, N-acyl-ethanolamine phospholipids; stimulators of glucagon-like peptide 1 receptors (e.g., glucagon-like peptide 1); polyphenol containing compounds such as resveratrol; chelating compounds; apoptosis-related protease inhibitors; compounds that reduce new protein synthesis; radiotherapeutic agents; photodynamic therapy agents; gene therapy agents; genetic modulators; auto-immune modulators that prevent damage to nerves or portions of nerves (e.g., demyelination) such as glatimir; myelin inhibitors such as anti-NgR Blocking Protein, NgR(310)ecto-Fc; other immune modulators such as FK506 binding proteins (e.g., FKBP51); and dry eye medications such as cyclosporine A, delmulcents, and sodium hyaluronate. 
     Other therapeutic agents that may be used include: other beta-blocker agents such as acebutolol, atenolol, bisoprolol, carvedilol, asmolol, labetalol, nadolol, penbutolol, and pindolol; other corticosteroidal and non-steroidal anti-inflammatory agents such aspirin, betamethasone, cortisone, diflunisal, etodolac, fenoprofen, fludrocortisone, flurbiprofen, hydrocortisone, ibuprofen, indomethacins, ketoprofen, meclofenamate, mefenamic acid, meloxicam, methylprednisolone, nabumetone, naproxen, oxaprozin, prednisolone, prioxicam, salsalate, sulindac and tolmetin; COX-2 inhibitors like celecoxib, rofecoxib and Valdecoxib; other immune-modulating agents such as aldesleukin, adalimumab (HUMIRA®), azathioprine, basiliximab, daclizumab, etanercept (ENBREL®), hydroxychloroquine, infliximab (REMICADE®), letiunomide, methotrexate, mycophenolate mofetil, and sulfasalazine; other anti-histamine agents such as loratadine, desloratadine, cetirizine, diphenhydramine, chlorpheniramine, dexchlorpheniramine, clemastine, cyproheptadine, fexofenadine, hydroxyzine and promethazine; other anti-infective agents such as aminoglycosides such as amikacin and streptomycin; anti-fungal agents such as amphotericin B, caspofungin, clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine and nystatin; anti-malarial agents such as chloroquine, atovaquone, metioquine, primaquine, quinidine and quinine; anti-mycobacterium agents such as ethambutol, isoniazid, pyrazinamide, rifampin and rifabutin; anti-parasitic agents such as albendazole, mebendazole, thiabendazole, metronidazole, pyrantel, atovaquone, iodoquinaol, ivermectin, paromycin, praziquantel, and trimatrexate, other anti-viral agents, including anti-CMV or anti-herpetic agents such as acyclovir, cidofovir, famciclovir, gangciclovir, valacyclovir, valganciclovir, vidarabine, trifluridine and foscarnet; protease inhibitors such as ritonavir, saquinavir, lopinavir, indinavir, atazanavir, amprenavir and nelfinavir; nucleotide/nucleoside/non-nucleoside reverse transcriptase inhibitors such as abacavir, ddI, 3TC, d4T, ddC, tenofovir and emtricitabine, delavirdine, efavirenz and nevirapine; other anti-viral agents such as interferons, ribavirin and trifluridiene; other anti-bacterial agents, including cabapenems like ertapenem, imipenem and meropenem; cephalosporins such as cefadroxil, cefazolin, cefdinir, cefditoren, cephalexin, cefaclor, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, cefpodoxime, cefprozil, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime and loracarbef ; other macrolides and ketolides such as azithromycin, clarithromycin, dirithromycin and telithromycin; penicillins (with and without clavulanate) including amoxicillin, ampicillin, pivampicillin, dicloxacillin, nafcillin, oxacillin, piperacillin, and ticarcillin; tetracyclines such as doxycycline, minocycline and tetracycline; other anti-bacterials such as aztreonam, chloramphenicol, clindamycin, linezolid, nitrofurantoin and vancomycin; alpha blocker agents such as doxazosin, prazosin and terazosin; calcium-channel blockers such as amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil; other anti-hypertensive agents such as clonidine, diazoxide, fenoldopan, hydralazine, minoxidil, nitroprusside, phenoxybenzamine, epoprostenol, tolazoline, treprostinil and nitrate-based agents; anti-coagulant agents, including heparins and heparinoids such as heparin, dalteparin, enoxaparin, tinzaparin and fondaparinux; other anti-coagulant agents such as hirudin, aprotinin, argatroban, bivaliiridin, desirudin, lepirudin, warfarin and ximelagatran; anti-platelet agents such as abciximab, clopidogrel, dipyridamole, optifibatide, ticlopidine and tirofiban; prostaglandin PDE-5 inhibitors and other prostaglandin agents such as alprostadil, carboprost, sildenafil, tadalafil and vardenafil; thrombin inhibitors; antithrombogenic agents; anti-platelet aggregating agents; thrombolytic agents and/or fibrinolytic agents such as alteplase, anistreplase, reteplase, streptokinase, tenecteplase and urokinase; anti-proliferative agents such as sirolimus, tacrolimus, everolimus, zotarolimus, paclitaxel and mycophenolic acid; hormonal-related agents including levothyroxine, fluoxymestrone, methyltestosterone, nandrol one, oxandrolone, testosterone, estradiol, estrone, estropipate, clomiphene, gonadotropins, hydroxyprogesterone, levonorgestrel, medroxyprogesterone, megestrol, mifepristone, norethindrone, oxytocin, progesterone, raloxifene and tamoxifen; anti-neoplastic agents, including alkylating agents such as carmustine lomustine, melphalan, cisplatin, fluorouracil3, and procarbazine antibiotic-like agents such as bleomycin, daunorubicin, doxorubicin, idarubicin, mitomycin and plicamycin; anti proliferative agents (such as 1,3-cis retinoic acid, 5-fluorouracil, taxol, rapamycin, mitomycin C and cisplatin); antimetabolite agents such as cytarabine, fludarabine, hydroxyurea, mercaptopurine and 5-fluorouracil (5-FU), immune modulating agents such as aldesleukin, imatinib, rituximab and tositumomab; mitotic inhibitors docetaxel, etoposide, vinblastine and vincristine; radioactive agents such as strontium-89; and other anti-neoplastic agents such as irinotecan, topotecan and mitotane. 
     In some embodiments, the therapeutic agent is delivered through the implant to the desired location in the eye, such as the uveoscleral outflow pathway. In some embodiments, the therapeutic agent is delivered to the uveoscleral outflow pathway in combination with a therapeutic agent delivered via trans pars plana vitrectomy, thereby delivering a therapeutic agent to both sides of the retina. In some embodiments, the implant can improve access of topical medication to the posterior uvea. In some embodiments, the implant is used to delivery a topical medication to treat a chorio-retinal disease. 
     If desired, more than one implant of the same or different type may be implanted. For example, the implants disclosed herein may be used in combination with trabecular bypass shunts, such as those disclosed in U.S. Patent Publication 2004/0050392, and those described in U.S. Patent Publication 2005/0271704, filed Mar. 18, 2005, the entirety of which is incorporated herein by reference and made a part of this specification and disclosure. Additionally, implantation may be performed in combination with other surgical procedures, such as cataract surgery. All or a portion of the implant may be coated, e.g. with heparin, preferably in the flow path, to reduce blood thrombosis or tissue restenosis. 
     If desired, a multiplicity of implants having different flow capacities and/or lumen sizes may be implanted. For example, a single “large” lumen implant can be implanted first, and subsequent, depending on the pressure response to the first stent, a second can be added with potentially smaller flow capacity in order to “fine tune” the desired IOP. For example, the IOP of a first patient can safely be brought down to approximately 12-18 mm Hg, and once the flow capacity of the first stent is matched with the IOP reduction, a calculation can be made as to what additional outflow is required to achieve target pressures of, for example, approximately 8-12 mmHg. An appropriately sized implant can be added to accomplish the target pressure. Both implants can be proactively added at the same time based on calculated outflow requirements. Alternatively, the implants can be added sequentially as described above based on the measured effect of the first implant. 
     Kits 
     According to some embodiments, a kit (e.g., system or collection of items for a common purpose) for addressing ocular disorders is provided. The tem “kit” as used herein should be given its ordinary meaning and should include any system, grouping and/or collection of devices, systems, components, features, materials and/or the like provided for a common goal. In one embodiment, the kit comprises one or more of the following: a delivery apparatus (such as the multiple-implant delivery apparatus  200  described herein), a plurality of drainage implants (such as the drainage implants described herein), an incising member, and a sensor (such as a pressure sensor, an intraocular pressure sensor, an analyte sensor, a glucose sensor, or any other sensor configured for placement within an eye). In some embodiments, the drainage implants are pre-loaded within or on the delivery apparatus during manufacture and assembly prior to shipping. In other embodiments, the drainage implants are not pre-loaded. The kit can further comprise instructions for using the various devices, components and/or other features of the kit for a particular procedure or treatment protocol. For example, such instructions for use can include details regarding the order in which the devices, systems or other components are used, the duration of use and/or the like. 
     While certain embodiments of the disclosure have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the disclosure. Indeed, the novel methods, systems, and devices described herein may be embodied in a variety of other forms. For example, embodiments of one illustrated or described implant can be combined with embodiments of another illustrated or described implant. Moreover, the implants described above can be utilized for other purposes. For example, the implants can be used to drain fluid from the anterior chamber to other locations of the eye or outside the eye. Some embodiments have been described in connection with the accompanying drawings. However, it should be understood that the figures are not drawn to scale. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and/or rearranged. Furthermore, various omissions, substitutions and changes in the form of the methods, systems, and devices described herein may be made without departing from the spirit of the disclosure. 
     Conditional language, for example, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and/or steps. Thus, such conditional language is not generally intended to imply that features, elements and/or steps are in any way required for one or more embodiments or that one or more embodiments necessarily include logic for deciding, with or without user input or prompting, whether these features, elements and/or steps are included or are to be performed in any particular embodiment.