Abstract:
Methods of treating ocular disorders are disclosed, such as a method that includes inserting an implant in eye tissue, using a delivery instrument, such that an inlet portion of the implant is in an anterior chamber of an eye and an outlet portion of the implant is in a physiological outflow pathway; removing the delivery instrument from the eye without removing the implant; and conducting fluid comprising a therapeutic substance through the implant and into the physiological outflow pathway. Another method includes inserting an instrument into a physiologic outflow pathway through which aqueous humor drains from an anterior chamber of an eye; separating first and second walls of tissues which comprise the physiologic outflow pathway by injecting a fluid comprising a drug from the instrument while the instrument remains in the physiologic outflow pathway; and withdrawing the instrument following the injection with said fluid remaining within the eye such that the drug has a therapeutic effect on the eye.

Description:
CROSS REFERENCE TO RELATED APPLICATION  
       [0001]     This application is a continuation application of U.S. patent application Ser. No. 10/384,912, entitled “Fluid Infusion Methods for Glaucoma Treatment,” filed Mar. 7, 2003, now U.S. Pat. No. 7,186,232 B1, issued Mar. 6, 2007, which application claims the priority benefit of U.S. Provisional Application No. 60/362,405, entitled “Apparatus and Combination Therapy for Treating Glaucoma,” filed Mar. 7, 2002, and U.S. Provisional Application No. 60/363,980, entitled “Means and Procedures for Implanting a Glaucoma Shunt,” filed Mar. 14, 2002, the entireties of which are hereby incorporated by reference. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     1. Field of the Invention  
         [0003]     This invention relates to reducing intraocular pressure within the animal eye. More particularly, this invention relates to a treatment of glaucoma wherein aqueous humor is permitted to flow out of an anterior chamber of the eye through a surgically implanted pathway. Furthermore, this invention relates to directly dilating Schlemm&#39;s canal and/or aqueous collector channels by injecting fluid through the implanted pathway of a stent.  
         [0004]     2. Description of the Related Art  
         [0005]     A human eye is a specialized sensory organ capable of light reception and is able to receive visual images. Aqueous humor is a transparent liquid that fills the region between the cornea, at the front of the eye, and the lens. A trabecular meshwork, located in an anterior chamber angle formed between the iris and the cornea, serves as a drainage channel for aqueous humor from the anterior chamber, which maintains a balanced pressure within the anterior chamber of the eye.  
         [0006]     About two percent of people in the United States have glaucoma. Glaucoma is a group of eye diseases encompassing a broad spectrum of clinical presentations, etiologies, and treatment modalities. Glaucoma causes pathological changes in the optic nerve, visible on the optic disk, and it causes corresponding visual field loss, resulting in blindness if untreated. Lowering intraocular pressure is the major treatment goal in all glaucomas.  
         [0007]     In glaucomas associated with an elevation in eye pressure (intraocular hypertension), the source of resistance to outflow is mainly in the trabecular meshwork. The tissue of the trabecular meshwork allows the aqueous humor (hereinafter referred to as “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. Aqueous is continuously secreted by a ciliary body around the lens, so there is a constant flow of aqueous from the ciliary body to the anterior chamber of the eye. Pressure within the eye is determined by a balance between the production of aqueous and its exit through the trabecular meshwork (major route) and uveoscleral outflow (minor route). The portion of the trabecular meshwork adjacent to Schlemm&#39;s canal (the juxtacanilicular meshwork) causes most of the resistance to aqueous outflow.  
         [0008]     Glaucoma is broadly classified into two categories: closed-angle glaucoma, also known as angle closure glaucoma, and open-angle glaucoma. Closed-angle glaucoma is caused by closure of the anterior chamber angle by contact between the iris and the inner surface of the trabecular meshwork. Closure of this anatomical angle prevents normal drainage of aqueous from the anterior chamber of the eye. Open-angle glaucoma is any glaucoma in which the exit of aqueous through the trabecular meshwork is diminished while the angle of the anterior chamber remains open. For most cases of open-angle glaucoma, the exact cause of diminished filtration is unknown. Primary open-angle glaucoma is the most common of the glaucomas, and is often asymptomatic in the early to moderately advanced stages of glaucoma. Patients may suffer substantial, irreversible vision loss prior to diagnosis and treatment. However, there are secondary open-angle glaucomas that may include edema or swelling of the trabecular spaces (e.g., from corticosteroid use), abnormal pigment dispersion, or diseases such as hyperthyroidism that produce vascular congestion.  
         [0009]     All current therapies for glaucoma are directed toward decreasing intraocular pressure. Currently recognized categories of drug therapy for glaucoma include: (1) Miotics (e.g., pilocarpine, carbachol, and acetylcholinesterase inhibitors), (2) Sympathomimetics (e.g., epinephrine and dipivalylepinephxine), (3) Beta-blockers (e.g., betaxolol, levobunolol and timolol), (4) Carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide and ethoxzolamide), and (5) Prostaglandins (e.g., metabolite derivatives of arachindonic acid). Medical therapy includes topical ophthalmic drops or oral medications that reduce the production of aqueous or increase the outflow of aqueous. However, drug therapies for glaucoma are sometimes associated with significant side effects. The most frequent and perhaps most serious drawback to drug therapy is that patients, especially the elderly, often fail to correctly self-medicate. Such patients forget to take their medication at the appropriate times or else administer eye drops improperly, resulting in under- or overdosing. Because the effects of glaucoma are irreversible, when patients dose improperly, allowing ocular concentrations to drop below appropriate therapeutic levels, further permanent damage to vision occurs. Furthermore, current drug therapies are targeted to be deposited directly into the ciliary body where the aqueous is produced. And, current therapies do not provide for a continuous slow-release of the drug. When drug therapy fails, surgical therapy is pursued.  
         [0010]     Surgical therapy for open-angle glaucoma consists of laser trabeculoplasty, trabeculectomy, and implantation of aqueous shunts after failure of trabeculectomy or if trabeculectomy is unlikely to succeed. Trabeculectomy is a major surgery that is widely used and is augmented with topically applied anticancer drugs, such as 5-flurouracil or mitomycin-C to decrease scarring and increase the likelihood of surgical success.  
         [0011]     Approximately 100,000 trabeculectomies are performed on Medicare-age patients per year in the United States. This number would likely increase if ocular morbidity associated with trabeculectomy could be decreased. The current morbidity associated with trabeculectomy consists of failure (10-15%); infection (a life long risk of 2-5%); choroidal hemorrhage, a severe internal hemorrhage from low intraocular pressure, resulting in visual loss (1%); cataract formation; and hypotony maculopathy (potentially reversible visual loss from low intraocular pressure). For these reasons, surgeons have tried for decades to develop a workable surgery for the trabecular meshwork.  
         [0012]     The surgical techniques that have been tried and practiced are goniotomy/trabeculotomy and other mechanical disruptions of the trabecular meshwork, such as trabeculopuncture, goniophotoablation, laser trabecular ablation, and goniocurretage. These are all major operations and are briefly described below.  
         [0013]     Goniotomy and trabeculotomy are simple and directed techniques of microsurgical dissection with mechanical disruption of the trabecular meshwork. These initially had early favorable responses in the treatment of open-angle glaucoma. However, long-term review of surgical results showed only limited success in adults. In retrospect, these procedures probably failed due to cellular repair and fibrosis mechanisms and a process of “filling in.” Filling in is a detrimental effect of collapsing and closing in of the created opening in the trabecular meshwork. Once the created openings close, the pressure builds back up and the surgery fails.  
         [0014]     Q-switched Neodynium (Nd) YAG lasers also have been investigated as an optically invasive trabeculopuncture technique for creating full-thickness holes in trabecular meshwork. However, the relatively small hole created by this trabeculopuncture technique exhibits a filling-in effect and fails.  
         [0015]     Goniophotoablation is disclosed by Berlin in U.S. Pat. No. 4,846,172 and involves the use of an excimer laser to treat glaucoma by ablating the trabecular meshwork. This method did not succeed in a clinical trial. Hill et al. used an Erbium YAG laser to create full-thickness holes through trabecular meshwork (Hill et al., Lasers in Surgery and Medicine 11:341346, 1991). This laser trabecular ablation technique was investigated in a primate model and a limited human clinical trial at the University of California, Irvine. Although ocular morbidity was zero in both trials, success rates did not warrant further human trials. Failure was again from filling in of surgically created defects in the trabecular meshwork by repair mechanisms. Neither of these is a viable surgical technique for the treatment of glaucoma.  
         [0016]     Goniocurretage is an “ab interno” (from the inside), mechanically disruptive technique that uses an instrument similar to a cyclodialysis spatula with a microcurrette at the tip. Initial results were similar to trabeculotomy: it failed due to repair mechanisms and a process of filling in.  
         [0017]     Although trabeculectomy is the most commonly performed filtering surgery, viscocanalostomy (VC) and nonpenetrating trabeculectomy (NPT) are two new variations of filtering surgery. These are “ab externo” (from the outside), major ocular procedures in which Schlemm&#39;s canal is surgically exposed by making a large and very deep scleral flap. In the VC procedure, Schlemm&#39;s canal is cannulated and viscoelastic substance injected (which dilates Schlemm&#39;s canal and the aqueous collector channels). In the NPT procedure, the inner wall of Schlemm&#39;s canal is stripped off after surgically exposing the canal.  
         [0018]     Trabeculectomy, VC, and NPT involve the formation of an opening or hole under the conjunctiva and scleral flap into the anterior chamber, such that aqueous is drained onto the surface of the eye or into the tissues located within the lateral wall of the eye. These surgical operations are major procedures with significant ocular morbidity. When trabeculectomy, VC, and NPT are thought to have a low chance for success, a number of implantable drainage devices have been used to ensure that the desired filtration and outflow of aqueous through the surgical opening will continue. The risk of placing a glaucoma drainage device also includes hemorrhage, infection, and diplopia (double vision).  
         [0019]     All of the above embodiments and variations thereof have numerous disadvantages and moderate success rates. They involve substantial trauma to the eye and require great surgical skill in creating a hole through the full thickness of the sclera into the subconjunctival space. The procedures are generally performed in an operating room and involve a prolonged recovery time for vision. The complications of existing filtration surgery have prompted ophthalmic surgeons to find other approaches to lowering intraocular pressure.  
         [0020]     Because the trabecular meshwork and juxtacanilicular tissue together provide the majority of resistance to the outflow of aqueous, they are logical targets for surgical removal in the treatment of open-angle glaucoma. In addition, minimal amounts of tissue need be altered and existing physiologic outflow pathways can be utilized.  
         [0021]     As reported in Arch. Ophthalm. (2000) 118:412, glaucoma remains a leading cause of blindness, and filtration surgery remains an effective, important option in controlling glaucoma. However, modifying existing filtering surgery techniques in any profound way to increase their effectiveness appears to have reached a dead end. The article further states that the time has come to search for new surgical approaches that may provide better and safer care for patients with glaucoma.  
         [0022]     What is needed, therefore, is an extended, site-specific treatment method for placing a hollow trabecular microstent ab interno for diverting aqueous humor in an eye from the anterior chamber into Schlemm&#39;s canal. In some aspect of the present invention, it is provided a method for injecting fluid through the common hollow lumen of the microstent to therapeutically dilate Schlemm&#39;s canal and the aqueous collector channels.  
       SUMMARY OF THE INVENTION  
       [0023]     A device and methods are provided for improved treatment of intraocular pressure due to glaucoma. A hollow trabecular microstent is adapted for implantation within a trabecular meshwork of an eye such that aqueous humor flows controllably from an anterior chamber of the eye to Schlemm&#39;s canal, bypassing the trabecular meshwork. The trabecular microstent comprises a quantity of pharmaceuticals effective in treating glaucoma, which are controllably released from the device into cells of the trabecular meshwork and/or Schlemm&#39;s canal. Depending upon the specific treatment contemplated, pharmaceuticals may be utilized in conjunction with the trabecular microstent such that aqueous flow either increases or decreases as desired. Placement of the trabecular microstent within the eye and incorporation, and eventual release, of a proven pharmaceutical glaucoma therapy will reduce, inhibit or slow the effects of glaucoma.  
         [0024]     One aspect of the invention provides an axisymmetric trabecular microstent that is implantable within an eye. The microstent comprises an inlet section containing at least one lumen and one inlet opening, an outlet section having at least one lumen that connects to at least one outlet opening. In some aspect of the present invention, the microstent further comprises a flow-restricting member within the lumen that is configured to partially prevent back flow from passing through the flow-restricting member. The microstent further comprises a middle section that is fixedly attached to the outlet section having at least one lumen in fluid communication with the lumen of the outlet section. The middle section is fixedly attached to the inlet section and the lumen within the middle section is in fluid communication with the lumen of the inlet section. The device is configured to permit fluid entering the lumen of the inlet section to pass through the flow-restricting member, enter the lumen of the middle section, pass into the lumen of the outlet section, and then exit the outlet section.  
         [0025]     Another aspect of the invention provides a method of treating glaucoma. The method comprises providing fluid through the lumen of the microstent to therapeutically dilate the aqueous cavity. The term “aqueous cavity” herein refers to any one or more of the downstream aqueous passageways “behind” the trabecular meshwork, including, without limitation, Schlemm&#39;s canal, the aqueous collector channels, and episcleral veins. In one embodiment, the fluid contains therapeutic substance, including pharmaceuticals, genes, growth factors, enzymes and like. In another embodiment, the fluid contains sterile saline, viscoelastic, or the like. The mode of fluid injection may be a pulsed mode, an intermittent mode or a programmed mode. In one aspect, the pressure of the fluid therapy is effective to cause therapeutic effects on the tissue of the aqueous cavity. In another aspect, the fluid pressure is effective to cause the dilation of the aqueous cavity beyond the tissue elastic yield point for permanent (i.e., plastic) deformation. In other embodiment, the fluid is at an elevated pressure effective to cause plastic deformation for at least a portion of the aqueous cavity.  
         [0026]     Another aspect of the invention provides an apparatus for implanting a trabecular microstent within an eye and dilating the aqueous cavity. The apparatus comprises a syringe portion and a cannula portion that has proximal and distal ends. The proximal end of the cannula portion is attached to the syringe portion. The cannula portion further comprises a first lumen and at least one irrigating hole disposed between the proximal and distal ends of the cannula portion. The irrigating hole is in fluid communication with the lumen. The apparatus further includes a holder including a second lumen for holding the trabecular microstent. A distal end of the second lumen opens to the distal end of the cannula portion, and a proximal end of the second lumen is separated from the first lumen of the cannula portion. The holder holds the trabecular microstent during implantation of the device within the eye, and the holder releases the trabecular microstent when a practitioner activates deployment of the device.  
         [0027]     Another aspect of the invention provides a method of implanting a trabecular microstent within an eye. The method comprises creating a first incision in a cornea on a first side of the eye, wherein the first incision passes through the cornea into an anterior chamber of the eye. The method further comprises passing an incising device through the first incision and moving a distal end of the incising device across the anterior chamber to a trabecular meshwork residing on a second side of the eye, and using the incising device to create a second incision. The second incision is in the trabecular meshwork, passing from the anterior chamber through the trabecular meshwork into a Schlemm&#39;s canal. The method further comprises inserting the trabecular microstent into a distal space of a delivery applicator. The delivery applicator comprises a cannula portion having a distal end and a proximal end attached to a syringe portion. The cannula portion has at least one lumen and at least one irrigating hole disposed between proximal and distal ends of the cannula portion. The irrigating hole is in fluid communication with the lumen. The distal space comprises a holder that holds the trabecular microstent during delivery and releases the trabecular microstent when a practitioner activates deployment of the device. The method further comprises advancing the cannula portion and the trabecular microstent through the first incision, across the anterior chamber and into the second incision, wherein an outlet section of the trabecular microstent is implanted into Schlemm&#39;s canal while an inlet section of the trabecular microstent remains in fluid communication with the anterior chamber. The method still further comprises releasing the trabecular microstent from the holder of the delivery applicator.  
         [0028]     One aspect of the invention includes a method of treating glaucoma, including inserting a stent through an incision in an eye; the stent having an inflow portion that is in fluid communication with an outflow portion of the stent; transporting the stent from the incision through the anterior chamber of the eye to an aqueous cavity of the eye, such that the inflow portion of the stent is positioned in the anterior chamber and the outflow portion of the stent is positioned at the aqueous cavity; and infusing fluid from the inflow portion to the outflow portion of the stent.  
         [0029]     Some embodiments further include closing the incision, leaving the stent in the eye such that the inflow portion of the stent is positioned in the anterior chamber of the eye and the outflow portion of the stent is positioned in Schlemm&#39;s canal.  
         [0030]     Some embodiments further include positioning the stent such that fluid communicating from the inflow portion to the outflow portion of the stent bypasses the trabecular meshwork of the eye.  
         [0031]     In some embodiments fluid is infused through a lumen of the stent. In some embodiments the aqueous cavity is Schlemm&#39;s canal. In other embodiments the aqueous cavity is an aqueous collector channel.  
         [0032]     In some embodiments, the infusing further comprises injecting the fluid in at least one of a pulsed mode, an intermittent mode, and a programmed mode.  
         [0033]     In some embodiments the infusing of fluid is at a pressure sufficient to cause plastic deformation of at least a portion of the aqueous cavity.  
         [0034]     In a preferred arrangement, the fluid is at least one of a salt solution or viscoelastic.  
         [0035]     In some arrangements the infusing further comprises coupling the inflow portion of the stent with a fluid delivery element that transmits the fluid to the stent. In an embodiment the coupling comprises securing a screw thread arrangement of the fluid delivery element with a receiving thread arrangement of the stent.  
         [0036]     In certain preferred arrangements, the fluid comprises a therapeutic substance such as a pharmaceutical, a gene, a growth factor, and/or an enzyme.  
         [0037]     In other preferred arrangements, the fluid comprises the fluid comprises a therapeutic substance such as an antiglaucoma drug, a beta-adrenergic antagonist, a TGF-beta compound, and/or an antibiotic.  
         [0038]     Some embodiments provide that a temperature of the fluid is raised sufficiently to enhance the plastic deformation. And some embodiments provide that a pH of the fluid is adjusted sufficiently to enhance the plastic deformation.  
         [0039]     In some arrangements the method further includes vibrating a tissue of the eye.  
         [0040]     One aspect of the invention includes a method of treating glaucoma, including inserting a stent through an incision in an eye; the stent having an inflow portion that is in fluid communication with an outflow portion of the stent; positioning the stent such that the inflow portion of the stent is positioned in the anterior chamber of the eye and the outflow portion of the stent is positioned at an aqueous cavity; and infusing fluid from the inflow portion to the outflow portion of the stent.  
         [0041]     In some arrangements the aqueous cavity is Schlemm&#39;s canal. In certain arrangements, the method further comprises positioning the stent such that the outflow portion of the stent is in Schlemm&#39;s canal. In some arrangements the aqueous cavity is an aqueous collector channel. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0042]      FIG. 1  is a coronal, cross-sectional view of an eye.  
         [0043]      FIG. 2  is an enlarged cross-sectional view of an anterior chamber angle of the eye of  FIG. 1 .  
         [0044]      FIG. 3  is an oblique elevation view of one embodiment of an axisymmetric trabecular microstent.  
         [0045]      FIG. 4  is a detailed view of the proximal section of the microstent of  FIG. 3 .  
         [0046]      FIG. 5  is an applicator for delivering a microstent and infusing fluid for therapeutic treatment.  
         [0047]      FIG. 6  is an enlarged, cross-sectional view of a preferred method of implanting a trabecular microstent within an eye. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0048]     The preferred embodiments of the present invention described below relate particularly to surgical and therapeutic treatment of glaucoma through reduction of intraocular pressure. While the description sets forth various embodiment specific details, it will be appreciated that the description is illustrative only and should not be construed in any way as limiting the invention. Furthermore, various applications of the invention, and modifications thereto, which may occur to those who are skilled in the art, are also encompassed by the general concepts described below.  
         [0049]      FIG. 1  is a cross-sectional view of an eye  10 , while  FIG. 2  is a close-up view showing the relative anatomical locations of a trabecular meshwork  21 , an anterior chamber  20 , and a Schlemm&#39;s canal  22 . A sclera  11  is a thick collagenous tissue that covers the entire eye  10  except a portion that is covered by a cornea  12 . The cornea  12  is a thin transparent tissue that focuses and transmits light into the eye and through a pupil  14 , which is a circular hole in the center of an iris  13  (colored portion of the eye). The cornea  12  merges into the sclera  11  at a juncture referred to as a limbus  15 . A ciliary body  16  extends along the interior of the sclera  11  and is coextensive with a choroid  17 . The choroid  17  is a vascular layer of the eye  10 , located between the sclera  11  and a retina  18 . An optic nerve  19  transmits visual information to the brain and is the anatomic structure that is progressively destroyed by glaucoma.  
         [0050]     The anterior chamber  20  of the eye  10 , which is bound anteriorly by the cornea  12  and posteriorly by the iris  13  and a lens  26 , is filled with aqueous humor (hereinafter referred to as “aqueous”). Aqueous is produced primarily by the ciliary body  16 , then moves anteriorly through the pupil  14  and reaches an anterior chamber angle  25 , formed between the iris  13  and the cornea  12 . In a normal eye, aqueous is removed from the anterior chamber  20  through the trabecular meshwork  21 . Aqueous passes through the trabecular meshwork  21  into Schlemm&#39;s canal  22  and thereafter through a plurality of aqueous veins  23 , 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 in the manner described above. Glaucoma is, in most cases, characterized by an excessive buildup of aqueous in the anterior chamber  20 , which leads to an increase in intraocular pressure. Fluids are relatively incompressible, and thus intraocular pressure is distributed relatively uniformly throughout the eye  10 .  
         [0051]     As shown in  FIG. 2 , the trabecular meshwork  21  is adjacent to a small portion of the sclera  11 . Exterior to the sclera  11  is a conjunctiva  24 . Traditional procedures that create a hole or opening for implanting a device through the tissues of the conjunctiva  24  and sclera  11  involve extensive surgery, as compared to surgery for implanting a device, as described herein, which ultimately resides entirely within the confines of the sclera  11  and cornea  12 . A microstent  81  is shown placed through trabecular meshwork  21  having a distal portion  83  disposed within Schlemm&#39;s canal  22  and a proximal portion  82  disposed within the anterior chamber  20  of the eye  10 .  FIG. 6  generally illustrates the use of one embodiment of a trabecular microstent  81  for establishing an outflow pathway, passing through the trabecular meshwork  21 , which is discussed in greater detail below.  
         [0052]      FIG. 3  illustrates a preferred embodiment of a hollow trabecular microstent  81 , which facilitates the outflow of aqueous from the anterior chamber  20  into Schlemm&#39;s canal  22 , and subsequently into the aqueous collectors and the aqueous veins so that intraocular pressure is reduced. In the illustrated embodiment, the trabecular microstent  81  comprises an inlet section  82 , having an inlet opening  86 , a middle section  84 , and an outlet section  83  having at least one opening  87 ,  88 . The middle section  84  may be an extension of, or may be coextensive with, the inlet section  82 . The device  81  comprises at least one lumen  85  within section  84 , which is in fluid communication with the inlet opening  86  and the outlet opening  87 ,  88 , thereby facilitating transfer of aqueous through the device  81 . In one aspect, the outlet side openings  88 , each of which is in fluid communication with the lumen  85  for transmission of aqueous, are arranged spaced apart around the circumferential periphery  80  of the outlet section  83 . In another aspect, the outlet openings  88  are located and configured to enable jet-like infusing fluid impinging any specific region of Schlemm&#39;s canal tissue suitably for tissue stimulation.  
         [0053]     As will be apparent to a person skilled in the art, the lumen  85  and the remaining body of the outlet section  83  may have a cross-sectional shape that is oval, circular, or other appropriate shape. Preferably, the middle section  84  has a length that is roughly equal to a thickness of the trabecular meshwork  21 , which typically ranges between about 100 μm and about 300 μm.  
         [0054]     To further stent or open Schlemm&#39;s canal after implanting the axisymmetric device  81 , a plurality of elevated (that is, protruding axially) supports or pillars  89  is located at the distal-most end of the outlet section  83  sized and configured for allowing media (for example, aqueous, liquid, balanced salt solution, viscoelastic fluid, therapeutic agents, or the like) to be transported freely.  
         [0055]     The microstent  81  may further comprises a flow-restricting member  90 , which is tightly retained within a lumen  85 . The flow-restricting member  90  serves to selectively restrict at least one component in blood from moving retrograde, i.e., from the outlet section  83  into the anterior chamber  20  of the eye  10 . Alternatively, the flow-restricting member  90  may be situated in any location within the device  81  such that blood flow is restricted from retrograde motion. The flow-restricting member  90  is sized and configured for maintaining the pressure of the infused fluid within the aqueous cavity for a suitable period of time. The flow-restricting member  90  may, in other embodiments, be a filter made of a material selected from the following filter materials: expanded polytetrafluoroethylene, cellulose, ceramic, glass, Nylon, plastic, and fluorinated material such as polyvinylidene fluoride (“PVDF”) (trade name: Kynar, by DuPont).  
         [0056]     The trabecular microstent  81  may be made by molding, thermo-forming, or other micro-machining techniques. The trabecular microstent  81  preferably comprises a biocompatible material such that inflammation arising due to irritation between the outer surface of the device  81  and the surrounding tissue is minimized. Biocompatible materials which may be used for the device  81  preferably include, but are not limited to, titanium, stainless steel, medical grade silicone, e.g., Silastic™, available from Dow Corning Corporation of Midland, Mich.; and polyurethane, e.g., Pellethane™, also available from Dow Corning Corporation. In other embodiments, the device  81  may comprise other types of biocompatible material, such as, by way of example, polyvinyl alcohol, polyvinyl pyrolidone, collagen, heparinized collagen, polytetrafluoroethylene, expanded polytetrafluoroethylene, fluorinated polymer, fluorinated elastomer, flexible fused silica, polyolefin, polyester, polysilicon, and/or a mixture of the aforementioned biocompatible materials, and the like. In another aspect, the microstent is made of a biodegradable material selected from a group consisting of poly(lactic acid), polyethylene-vinyl acetate, poly(lactic-co-glycolic acid), poly(D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate), poly(caprolactone), poly(glycolic acid), and copolymer thereof.  
         [0057]     In still other embodiments, composite biocompatible material may be used, wherein a surface material may be used in addition to one or more of the aforementioned materials. For example, such a surface material may include polytetrafluoroethylene (PTFE) (such as Teflon™), polyimide, hydrogel, heparin, therapeutic drugs (such as beta-adrenergic antagonists, TGF-beta, and other anti-glaucoma drugs, or antibiotics), and the like.  
         [0058]     As is well known in the art, a device coated or loaded with a slow-release substance can have prolonged effects on local tissue surrounding the device. The slow-release delivery can be designed such that an effective amount of substance is released over a desired duration. “Substance,” as used herein, is defined as any therapeutic or active drug that can stop, mitigate, slow-down or reverse undesired disease processes.  
         [0059]     In one embodiment, the device  81  may be made of a biodegradable (also including bioerodible) material admixed with a substance for substance slow-release into ocular tissues. In another embodiment, polymer films may function as substance containing release devices whereby the polymer films may be coupled or secured to the device  81 . The polymer films may be designed to permit the controlled release of the substance at a chosen rate and for a selected duration, which may also be episodic or periodic. Such polymer films may be synthesized such that the substance is bound to the surface or resides within a pore in the film so that the substance is relatively protected from enzymatic attack. The polymer films may also be modified to alter their hydrophilicity, hydrophobicity and vulnerability to platelet adhesion and enzymatic attack.  
         [0060]     The device  81  may be used for a direct release of pharmaceutical preparations into ocular tissues. As discussed above, the pharmaceuticals may be compounded within the device  81  or form a coating on the device  81 . Any known drug therapy for glaucoma may be utilized.  
         [0061]      FIG. 4  shows a detailed view of the proximal section  82  of the microstent  81  of  FIG. 3 . In some aspect, the proximal section  82  has a bottom peripheral surface  91  that is about perpendicular to the lumen  85  of the microstent  81 . A receiving thread arrangement  95  is appropriately located on the peripheral surface  91 . The receiving thread arrangement  95  is sized and configured to releasably receive a screw thread arrangement  96  for coupling together, wherein the screw thread arrangement  96  is disposed at the distal end  97  of a fluid delivery element  94  which has a lumen  93  for transporting the infusing fluid into the aqueous cavity for therapeutic purposes. The coupling of the receiving thread arrangement  95  and the screw thread arrangement  96  makes the fluid infusion through the lumen  85  leak-proof enabling pressurized the aqueous cavity.  
         [0062]      FIG. 5  shows a distal portion  57  of an applicator  55  for delivering a microstent  81  and infusing fluid for therapeutic treatment. The distal portion  57  comprises a distal cutting means  42  sharp enough for creating an incision on the cornea and also creating an opening on trabecular meshwork  21  for stent placement. The axisymmetric microstent  81  is snugly placed within the lumen  43  of the applicator  55  and retained by a plurality of stent retaining members  45 . The microstent  81  is deployed from the applicator  55  once the distal section  83  passes beyond the edge of the trabecular meshwork  21 . In one aspect, the stent deployment is facilitated by a plunger-type deployment mechanism  44  with an associated deployment actuator  61  mounted on the handle  62  of the applicator  55  (see  FIG. 6 ).  
         [0063]     The microstent  81  may be releasably coupled with a fluid delivery element  94  at any convenient time during the procedures. In one aspect, the screw-unscrew coupling steps between the microstent  81  and the fluid delivery element  94  is carried out by suitably rotating the fluid delivery element  94  with reference to the stent receiving thread arrangement  95 , wherein the associated rotating mechanism  63  is located at the handle  62  of the applicator  55 .  
         [0064]     As will be appreciated by those of ordinary skill in the art, the device  81  may advantageously be practiced with a variety of sizes and shapes without departing from the scope of the invention. Depending upon the distance between the anterior chamber  20  and the drainage vessel (e.g., a vein) contemplated, the devices  81  may have a length ranging from about 0.05 centimeters to over 1 centimeter. Preferably, the device  81  has an outside diameter ranging between about 30 μm and about 500 μm, with the lumen  85  having diameters ranging between about 20 μm and about 250 μm, respectively. In addition, the device  81  may have a plurality of lumens to facilitate transmission of multiple flows of aqueous or infusing fluid.  
         [0065]     One preferred method for increasing aqueous outflow in the eye  10  of a patient, to reduce intraocular pressure therein, comprises bypassing the trabecular meshwork  21 . In operation, the middle section  84  of the device  81  is advantageously placed across the trabecular meshwork  21  through a slit or opening. This opening can be created by use of a laser, a knife, thermal energy (radiofrequency, ultrasound, microwave), cryogenic energy, or other surgical cutting instrument. The opening may advantageously be substantially horizontal, i.e., extending longitudinally in the same direction as the circumference of the limbus  15  ( FIG. 2 ). Other opening directions may also be used, as well. The opening may advantageously be oriented at any angle, relative to the circumference of the limbus  15 , that is appropriate for inserting the device  81  through the trabecular meshwork  21  and into Schlemm&#39;s canal  22  or other outflow pathway, as will be apparent to those skilled in the art. Furthermore, the outlet section  83  may be positioned into fluid collection channels of the natural outflow pathways. Such natural outflow pathways include Schlemm&#39;s canal  22 , aqueous collector channels, aqueous veins, and episcleral veins.  
         [0066]      FIG. 6  generally illustrates a preferred method by which the trabecular microstent  81  is implanted within the eye  10 . In the illustrated method, a delivery applicator  55  is provided, which preferably comprises a syringe portion  64  and a cannula portion  65 , which contains at least one lumen  43  in fluid communication with the fluid supply  66 . The cannula portion  65  preferably has a size of about 30 gauge. However, in other embodiments, the cannula portion  65  may have a size ranging between about 16 gauges and about 40 gauges. A holder  56  at the distal portion  57  of the cannula portion  65  for holding the device  81  may advantageously comprise a lumen, a sheath, a clamp, tongs, a space, and the like.  
         [0067]     In the method illustrated in  FIG. 6 , the device  81  is placed into the lumen  43  of the delivery applicator  55  and then advanced to a desired implantation site within the eye  10 . The delivery applicator  55  holds the device  81  securely during delivery and releases it when the practitioner initiates deployment actuator  61  of the applicator  55 .  
         [0068]     In a preferred embodiment of trabecular meshwork surgery, a patient is placed in a supine position, prepped, draped, and appropriately anesthetized. A small incision  52  is then made through the cornea  12  with a self-trephining applicator  55 . The incision  52  preferably has a surface length less than about 1.0 millimeter in length and may advantageously be self-sealing. Through the incision  52 , the trabecular meshwork  21  is accessed, wherein an incision is made with a cutting means  42  enabling forming a hole on the trabecular meshwork  21  for stent placement. The hole on the trabecular meshwork can also be created with a tip having thermal energy or cryogenic energy. After the device  81  is appropriately implanted, the applicator  55  is withdrawn and the trabecular meshwork surgery is concluded.  
         [0069]     In some aspect of the present invention, it is provided a method for expanding or attenuating the capacity of the existing canal outflow system (also known as the “aqueous cavity”). This system could have become constricted or blocked due to age or other factors associated with glaucoma. In one aspect, a tight fluid coupling is established between an external pressured fluid source  66  and Schlemm&#39;s canal  22  through a microstent  81 . It is also advantageous to connect the external pressurized fluid source through a removable instrument (for example, a temporary applicator, catheter, cannula, or tubing) to Schlemm&#39;s canal ab interno for applying the fluid infusion therapy.  
         [0070]     Once the fluid coupling is established, the pressure in the canal is raised by injecting fluid or fluid with therapeutic substances. In some aspect of the present invention, a method is provided of treating glaucoma including infusing fluid into aqueous cavity from an anterior chamber end of a stent, wherein the fluid is at an elevated pressure above a baseline pressure of the aqueous cavity. The method further comprises placing a hollow trabecular microstent bypassing the trabecular meshwork, wherein the fluid is infused from the anterior chamber through a lumen of the microstent. The mode of fluid injection is selected from a group consisting of a pulsed mode, an intermittent mode, a programmed mode, or combination thereof. In one aspect, the pressure of the fluid therapy is effective to cause therapeutic effects on the tissue of the aqueous cavity. In another aspect, the fluid pressure is effective to cause the dilation of the aqueous cavity beyond the tissue elastic yield point for plastic permanent deformation. In other embodiment, the fluid is at an elevated pressure effective to cause plastic deformation for at least a portion of the aqueous cavity.  
         [0071]     The fluid may be a salt solution such as Balanced Salt Solution, a viscoelastic (such as Healon), any other suitable viscous or non-viscous liquid, or suitable liquid loaded with drug at a concentration suitable for therapeutic purposes without causing safety concerns. A combination of liquids may also be used. The pressure is raised at an appropriate rate of rise to an appropriate level and for an appropriate length of time, as determined through development studies, to provide for the expansion of the outflow structures and/or a clearing of any blockages within them. The procedure can be augmented with other aids to enhance its effectiveness. These aids may include heat, vibration (sonic or ultrasonic), pulsation of a pressure front, pH, drugs, etc. It is intended that the aqueous cavity be expanded (attenuation or tissue stimulation) by this procedure resulting in an increased capacity for inflow and outflow of Schlemm&#39;s canal.  
         [0072]     In some aspect of the present invention, it is provided a method for using a removable applicator, catheter, cannula, or tubing that is placed ab interno through the trabecular meshwork into the aqueous cavity of an eye adapted for infusing therapeutic liquid into the aqueous cavity.  
         [0073]     In some aspect of the present invention, it is disclosed a method of treating glaucoma, the method including: providing at least one pharmaceutical substance incorporated into an axisymmetric trabecular microstent; implanting the microstent within a trabecular meshwork of an eye such that a first end of the microstent is positioned in an anterior chamber of the eye while a second end is positioned in a Schlemm&#39;s canal, wherein the first and second ends of the microstent establish a fluid communication between the anterior chamber and the Schlemm&#39;s canal; and allowing the microstent to release a quantity of the pharmaceutical substance into the eye. In one embodiment, the method further comprises a step of infusing fluid into the Schlemm&#39;s canal from the anterior chamber through a lumen of the microstent, wherein the fluid is at an elevated pressure above a baseline pressure of the Schlemm&#39;s canal.  
         [0074]     Although preferred embodiments of the invention have been described in detail, certain variations and modifications will be apparent to those skilled in the art, including embodiments that do not provide all of the features and benefits described herein. Accordingly, the scope of the present invention is not to be limited by the illustrations or the foregoing descriptions thereof, but rather solely by reference to the appended claims and their equivalents.