Abstract:
The present invention provides a microfistula tube including a soluble duct, defining a drainage canal having an inner surface, the duct being biocompatible, wherein the microfistula tube is coated with and/or incorporates biological for forming a basement membrane, or an intracellular matrix and a basement membrane. The biological cells may coat the inner surface of the drainage canal, and the microfistula tube may be made of a mouldable material or an absorbable material. The invention also provides an implantation system for the microfistula tube including a microfistula tube and a surgical instrument including an outer tube for penetrating body tissue, an inner tube, and an innermost rod, wherein the outer tube, the inner tube and the innermost rod are coaxial, the outer tube is adapted to receive said microfistula tube, whereby the inner tube may be used to push the microfistula tube into position and the innermost rod provides mechanical support during implantation of the microfistula tube.

Description:
This invention relates to a microfistula tube for the creation of microfistulae within the body, to be used for example to drain unwanted aqueous fluid, and a method and apparatus for the insertion into the body of a microfistula tube. In a preferred embodiment the microfistula tube is used for drainage of excess fluid in the eye. 
     Existing devices for the drainage of excessive aqueous fluid within the body, and most especially to control intraocular pressure in advanced refractory glaucoma, have been made of materials such as horse-hair, silk thread, gold foil, autologous canaliculus, tantalum wire, glass, platinum, polymethylmethacrylate, polyethylene, gelatin and autologous cartilage. Various devices made of these materials have been inserted, for example, in the anterior chamber of the eye under a conjunctival or scleral flap extending into the anterior subconjunctival space. However, problems frequently associated with existing devices include foreign-body reactions leading to fibroblast proliferation and sub-conjunctival fibrosis formation around the posterior exit of the drainage implant. Commonly, existing devices require large incisions of 1 mm×3 mm or even larger. Such incisions represent an extensive surgical injury and can lead to the formation of excessive quantities of scar tissue. Further, existing fistula tubes are mainly of non-biological materials and operate in far from physiological conditions. Such a fistula tube may generate an adverse tissue response, which causes blockage of the fistula tube resulting in uncontrolled eye pressure and ultimately negates any beneficial effects. More recent developments have attempted to protect the posterior exit of the drainage tube and develop posterior shunting of aqueous fluid to an equatorial sub-Tenon&#39;s collecting device. 
     These developments include a modified Krupin-Denver valve, the Schocket implant, the Joseph valve, and the Molteno implant. 
     An object of the present invention is to provide a biological microfistula tube subject to reduced rejection effects, that will lead to the formation of a microfistula for permanent or long-term aqueous fluid bypass, with minimal overdraining, and tending to impede wound healing processes and hence the closure of the drainage pathway. Further objects of the invention are to provide such a biological microfistula tube generating minimal tissue reaction, and matching outflow resistance, to allow the control of eye pressure and reduce surgical complications. A further object of the present invention is to provide a method and apparatus for the implantation of the biological microfistula tube. 
     According to a first broad aspect of the present invention there is provided a microfistula tube including: 
     a soluble duct, defining a drainage canal having an inner surface, the duct being biocompatible, wherein 
     said microfistula tube is coated with and/or incorporates biological cells for forming a basement membrane, or an intracellular matrix and a basement membrane. 
     Preferably the biological cells coat the inner surface of the drainage canal. 
     Preferably the microfistula tube is made of a mouldable material. 
     Preferably the microfistula tube is made of absorbable material. 
     Any suitable biocompatible material may be used, provided it permits the adherence of a basement membrane to the inner surface of the microfistula tube, and permits host endothelial or epithelial cells to grow in and coat the inner surface, while permitting minimal tissue reaction. Thus, the microfistula tube may be placed into a body, but will be incorporated into surrounding tissue or absorbed by the body over time. The biological cells—whose type will depend on the location where the microfistula tube is implanted—will provide a biological lining of the drainage pathway (i.e. microfistula) formed within the body by the microfistula tube, and inhibit the wound healing processes that would tend to occlude the drainage pathway. These cells will also reduce rejection effects. The biological cells, which will eventually form a permanent or long-lived endothelial, epithelial or similar lining of the drainage pathway formed by the microfistula tube minimize the tendency for fibroblast proliferation and the occlusion of the pathway. Consequently a microfistula tube size smaller than has been feasible with prior art devices or techniques may be employed, thereby reducing the risk of overdraining the aqueous fluid. 
     Preferably the biological cells are endothelial or trabecular meshwork cells. 
     Preferably the microfistula tube is made of gelatin or collagen. 
     By using a substance such as gelatin or collagen the mechanical and absorption properties of the tube may readily be manipulated, and the microfistula tube given the required rigidity and absorption properties. 
     Preferably the microfistula tube is sufficiently rigid to allow ready insertion into a living body. 
     Preferably the microfistula tube is a tube with a circular cross-section. 
     Preferably the outer surface of the microfistula tube tapers towards its forward end to facilitate its insertion into body tissues. Thus, the microfistula tube may be narrower at the forward end so that it can more easily be pushed into the relevant tissues of the body. 
     Preferably the duct is provided with one or more generally rearwardly projecting barbs or a generally rearwardly projecting skirt. Preferably the one or more barbs or said skirt is near the forward end of said microfistula tube. Thus, once the microfistula tube is in place it will not easily be able to move back along the path of insertion and hence be dislodged. 
     Preferably the rearward end of said microfistula tube has thicker walls to provide improved area and strength to allow the microfistula tube to be pushed into place by pressing against the rear end of the microfistula tube. 
     Preferably the rearward end of the microfistula tube has an increased outer perimeter size to prevent the microfistula tube from advancing beyond the point of implantation. 
     Thus, the rear end of the microfistula tube has an increased perimeter or, when the microfistula is tubular, an increased outer diameter, both to provide a broader base against which pressure may be applied to insert the microfistula tube into body tissues, and also to prevent the microfistula tube from advancing further than the point of implantation. 
     Preferably the microfistula tube is adapted to form a passage from the anterior chamber to Schlemm&#39;s canal, and has an interior diameter of between 100 and 200 μm, and a length of between 1 and 3 mm. 
     More preferably the microfistula tube has an interior diameter of approximately 150 μm and a length of approximately 2 mm. 
     Alternatively the microfistula tube is adapted to form a passage from the anterior chamber to the anterior subconjunctival space and has an interior diameter of between 100 and 400 μm and a length of between 2 and 6 mm. 
     Preferably the microfistula tube has an interior diameter of between 250 and 350 μm. 
     More preferably the microfistula tube has an interior diameter of approximately 300 μm and a length of approximately 3 mm. 
     Alternatively the microfistula tube is adapted to form a passage from the anterior chamber to the episcleral vein, with an inner diameter of between 100 and 300 μm and a length of between 7 and 14 mm. 
     Preferably the microfistula tube has an inner diameter of approximately 150 μm and a length of approximately 10 mm. 
     In one embodiment the microfistula tube is adapted to form a passage from the vitreal cavity to the subarachnoid space of the optic nerve, and has an inner diameter of between 100 and 300 μm and a length of between 3 and 12 mm. 
     Preferably the microfistula tube has an inner diameter of approximately 150 μm and a length of approximately 6 mm. 
     Thus, the microfistula tube may be used in optical applications to shunt aqueous fluid from the anterior chamber into Schlemm&#39;s canal, the subconjunctival space, or the episcleral vein, or from the vitreal cavity to the subarachnoid space of the optic nerve. 
     According to second broad aspect of the present invention there is provided a microfistula tube implantation system including: 
     a microfistula tube as described above; and 
     a surgical instrument including an outer tube for penetrating body tissue, 
     an inner tube, and 
     an innermost rod, 
     wherein said outer tube, said inner tube and said innermost rod are coaxial, said outer tube is adapted to receive said microfistula tube, whereby the inner tube may be used to push the microfistula tube into position and the innermost rod provides mechanical support during implantation of the microfistula tube. 
     Thus, the outer tube can be used to penetrate body tissues (for example a cornea), and the inner tube can then be used to push the microfistula tube forward and out of the forward end of the outer tube. The innermost rod may be moved with the inner tube until the microfistula tube is in its final position, and then the innermost rod may be withdrawn, followed by the inner tube. The outer tube may then be withdrawn from the body. 
     Preferably said microfistula tube is adapted to receive said innermost rod. 
     Preferably the outer tube is a hypodermic-type tube. 
     Preferably the inner tube is blunt-ended. 
     Preferably the outer tube is of stainless steel. 
     Preferably the inner tube is of stainless steel. 
     Preferably the innermost rod is of tungsten. 
     Preferably the surgical instrument is adapted to be attached to an ultramicrosurgical system. 
     Preferably the surgical instrument is adapted to be manipulated by electric motors. 
     Thus, the surgical instrument is adapted to deliver the microfistula tube to the required location. For greatest precision, the surgical instrument is used with a microsurgical system powered by electric motors and the operational procedures are performed under an operation microscope and gonioscopic observation. 
     According to third broad aspect of the present invention there is provided a microfistula tube implantation system including: 
     a microfistula tube as described above; and 
     a surgical instrument including an outer tube for cutting and penetrating body tissue, and 
     an inner rod, 
     wherein said outer tube and said inner rod are coaxial, said outer tube is adapted to receive said microfistula tube and said inner rod, and said outer tube has a sharp forward end for cutting body tissue, whereby the outer tube may be used to create a passage to an implantation site for said microfistula tube, said inner rod may be used to position a microfistula tube at said site, and said inner rod and outer tube may be withdrawn from said site leaving said microfistula tube in position at said site. 
     Preferably the outer tube is a hypodermic-type tube. 
     Preferably the outer tube is of stainless steel. 
     Preferably the inner rod is of stainless steel. 
     Preferably the surgical instrument is adapted to be attached to an ultramicrosurgical system. 
     Preferably the surgical instrument is adapted to be manipulated by electric motors. 
     According to fourth broad aspect of the present invention there is provided a method for the implantation of a microfistula tube including: 
     introducing into the vicinity of a desired implantation location an implantation system as described above with said microfistula tube mounted on the innermost rod, 
     pushing the microfistula tube out of the outer tube and into a desired location by means of the inner tube, the rod moving in unison with the inner tube and the microfistula tube, 
     withdrawing the surgical instrument from the body. 
     Preferably the rod is withdrawn from the microfistula tube before the inner tube is withdrawn. 
     Preferably the rod and inner tube are withdrawn into the outer tube before the inner tube, outer tube and rod are withdrawn from the body. 
     Preferably the desired location is the anterior chamber. 
     According to fifth broad aspect of the present invention there is provided a method for the implantation of a microfistula tube including: 
     forming the passage with said outer tube of said implantation system as described above with said microfistula tube in said outer tube forward of said inner rod, 
     advancing said microfistula tube to said implantation site with said inner rod, 
     withdrawing said outer tube, 
     withdrawing said inner rod, and 
     withdrawing the surgical instrument. 
     Preferably the method includes withdrawing the outer tube partially, then withdrawing said inner rod partially, followed by withdrawing said inner rod and outer tube in unison. 
     Preferably the partial withdrawal of the outer tube continues until said forward of said outer tube is in the anterior chamber. 
     Preferably the method includes rotating said outer tube with a reciprocating motion while forming said passage to aid said cutting of said tissue. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Preferred embodiments of the invention will be described, by way of example, with reference to the accompanying drawings in which: 
     FIG. 1 is a view of a microfistula tube embodying the present invention; 
     FIG. 2 is a view of a microfistula tube and surgical instrument according to a further embodiment of the present invention; 
     FIG. 3 illustrates a method for the implantation of a microfistula tube according to a further embodiment of the present invention; 
     FIG. 4 is a further illustration of the method for the implantation of a microfistula tube shown in FIG. 3, wherein a surgical instrument and microfistula tube are shown having penetrated a cornea; 
     FIG. 5 shows a further stage in the method of FIG. 3, in which a microfistula tube has been moved into its final position in the eye; 
     FIG. 6 shows a further illustration of the method of FIG. 3, in which the supporting rod is shown withdrawn from the microfistula tube; 
     FIG. 7 is a further illustration of the method of FIG. 3, in which the inner tube and supporting rod are shown retracted into the outer hypodermic-type tube; 
     FIG. 8 is a further illustration of the method of FIG. 3, in which the completed method is shown with the microfistula tube implanted in the eye and the surgical instrument removed from the cornea; 
     FIG. 9 is a view of a surgical instrument and microfistula tube according to a further embodiment of the present invention; 
     FIG. 10 is a view of a method of implantation of the microfistula tube by means of the surgical instrument of FIG. 9, wherein the surgical instrument and microfistula tube are shown having penetrated a cornea; 
     FIG. 11 shows a further stage in the method of FIG. 10, in which the surgical instrument has been advanced to the subconjunctival space; 
     FIG. 12 shows a further illustration of the method of FIG. 10, in which the microfistula tube has been advanced to an implantation site; 
     FIG. 13 is a further illustration of the method of FIG. 10, in which the outer tube of the surgical instrument has been withdrawn to the anterior space; and 
     FIG. 14 is a further illustration of the method of FIG. 10, in which the nearly completed method is shown with the microfistula tube implanted in the eye and the surgical instrument withdrawn to the anterior space. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     A biological microfistula tube according to the present invention is shown generally at  10  in FIG.  1 . The microfistula tube  10  comprises a hollow tube which defines a drainage canal  15  with a forward end  12  terminating in a point to facilitate the penetration by the microfistula tube  10  of tissue and a rear end  14 . The rear end  14  of the microfistula tube  10  has thickened walls to strengthen the microfistula tube  10 , as implantation of the microfistula tube  10  will generally be performed by pushing the microfistula tube  10  into place by applying pressure to the rear end  14 . 
     The microfistula tube  10  is made from gelatin, as the mechanical and absorption properties of the gelatin can be manipulated by varying the degree of cross-linking and controlling the water content. The material can therefore be designed to have the required rigidity to withstand the implantation process, but be absorbed after a controllable period. In most instances this would be only a matter of days or weeks. 
     The microfistula tube incorporates biological cells. Such cells lead to the formation of a biological lining of the drainage canal, which inhibits the wound-healing processes that would tend to occlude the drainage pathway. These cells (not shown) are either endothelial cells or ocular trabecular meshwork cells. These cells would generally line the inner surface of the microfistula tube  10 , though other configurations are possible, such as incorporating the cells into the material of the microfistula tube  10 . 
     Optionally, the microfistula tube  10  can be provided with one or more rearward pointing barbs (not shown), preferably located near the forward end  12  and on the outer surface of the microfistula tube  10 . These barbs would resist the unwanted rearward movement of the microfistula tube  10  following implantation. The flared rear end  14  of the microfistula tube  10 , and the generally tapered profile of the microfistula tube  10 , will resist unwanted forward movement of the microfistula tube  10 . The thickening of the rear end  14  of the microfistula tube  10  can be extended forward some distance to further resist unwanted forward motion of the microfistula tube  10  after implantation. This thickened portion of the rearward end  14  may be terminated more abruptly than shown in FIG. 1, so that a substantially forward facing surface is provided for this purpose. Finally, the rearward pointing face  16  of the rear end  14  of the microfistula tube  10  may be recessed or otherwise adapted to receive the forward end of a surgical instrument, to facilitate implantation of the microfistula tube  10  by means of such an instrument. 
     A surgical instrument according to the present invention provided with a microfistula tube  10  is shown generally at  30  in FIG.  2 . The surgical instrument  30  shown in the Figure is adapted for the implantation of the microfistula tube  10  into the eye to form a drainage pathway from the anterior chamber to the subconjunctival space. The microfistula tube  10  shown in the Figure includes rearward pointing barbs and a recessed base, as discussed above. The surgical instrument  30  comprises an outer tube  32  in the form of a hypodermic-type stainless steel tube, an inner tube  34  in the form of a blunt-ended stainless steel tube, and an innermost rod  36  made of tungsten. The microfistula tube  10  is shown located around the forward end  38  of the innermost rod  36 . The innermost rod  36  may slide within the inner tube  34 , and the inner tube  34  may slide within the outer tube  32 . 
     The outer tube  32  is adapted to penetrate the cornea, while the inner tube  34  is adapted to push the microfistula tube  10  from the outer tube  32  and into its final position. The innermost rod  36  is adapted to provide mechanical support during the implantation of the microfistula tube  10 . 
     In use, the surgical instrument  30  would be attached to and manipulated by means of an ultramicrosurgical system, and the operation performed under an operation microscope and gonioscopic observation. All movement would be produced by electric motor. 
     It should be noted that the outer tube  32  is sharp at its forward end  40  to facilitate the penetration of the cornea. The inner tube  34  is rounded at its forward end  42 , and the rear end of the microfistula tube  10  has a corresponding recess, so that the end  42  of the inner tube  34  may be received by the base of the microfistula tube  10 . 
     A surgical implantation method according to the present invention is illustrated in FIGS. 3 to  8 . The method illustrated in these figures is for the implantation of a microfistula tube to form a passage, by way of the drainage canal  15 , between the anterior chamber  50  (see FIGS. 3 to  8 ) and the anterior subconjunctival space  52  (see FIGS. 3 to  8 ). The entry point is 2 mm anterior to the limbus on the temporal side (see FIG.  3 ). This entry point may also be a pivot point of an ultramicrosurgical system, if such a system is used to manipulate the surgical instrument. 
     The surgical instrument  30  provided with a microfistula tube  10  penetrates the cornea  48 , and enters the anterior chamber  50  (see FIG.  4 ). The insertion of the surgical instrument  30  continues until the outer tube  32  of the surgical instrument  30  reaches the centre of the pupil  55 . 
     The inner tube  34 , the innermost rod  36 , and the microfistula tube  10  are advanced further (see FIG.  5 ), until the innermost rod  36  with the microfistula tube  10  penetrates the trabecular meshwork and sclera  57  until the tip of the microfistula tube  10  reaches the subconjunctival space  52 . The innermost rod  36  is then withdrawn from the microfistula tube  10  (FIG.  6 ), and the innermost rod (now withdrawn into the inner tube  34 ) and the inner tube  34  are retracted into the outer tube  32  (FIG.  7 ). 
     Finally, the surgical instrument  30  is withdrawn from the eye, leaving the implanted microfistula tube  10  in position (FIG.  8 ). In practice, a suture would generally then be placed to close the corneal wound. 
     In this procedure, the microfistula tube  10  has an inner diameter of 100 μm and a length of 3 mm. In alternative embodiments, the microfistula tube  10  can be implanted to form a passage between the anterior chamber and Schlemm&#39;s canal, in which case the inner diameter of the microfistula tube  10  is 150 μm and its length is 2 mm. In another embodiment the microfistula tube  10  forms a passage between the anterior chamber and the episcleral vein, and has an inner diameter of 150 μm and a length of 10 mm. Alternatively, a microfistula tube of inner diameter 150 μm and length 6 mm may be used to form a passage from the vitreal cavity to subarachnoid space of the optic nerve. 
     In some embodiments of the present invention, when the inner tube  34 , the innermost rod  36 , and the microfistula tube  10  are advanced as shown in FIG. 5, the resistance to penetration of the surrounding tissues may be so high that the microfistula tube cannot penetrate these tissues and collapses under the force of the inner tube  34 . It may be preferable, therefore, to provide the outer tube at its forward end with a sharp end for cutting through the surrounding tissue. Referring to FIG. 9, which is a view of an alternative embodiment of the implantation system of the present invention, outer tube  60  is again a hypodermic-type stainless steel tube. Unlike outer tube  32  of the embodiment illustrated in FIG. 2, however, the forward end  62  of outer tube  60  is sharpened and the opening  64  at the forward end  62  faces forwardly rather than obliquely. Stainless steel inner rod  66  is provided within outer tube  60  and microfistula tube  68  is positioned forward of inner rod  66 . Microfistula tube  68  will generally be substantially identical to those described above, but may lack the reinforced base of the above embodiments. 
     A method of implantation of a microfistula tube by means of this embodiment of the surgical instrument is illustrated in FIGS. 10 to  14 . The method illustrated in these figures is again for the implantation of a microfistula tube between the anterior chamber and the anterior subconjunctival space. Referring to FIG. 10, outer tube  60  is preferably rotated to assist the cutting of body tissues. This rotation alternates rapidly in direction so that tissue is cut by the tube  60 . The outer tube  60  penetrates the cornea  48 , and enters the anterior chamber  50 . Inner rod  66  is not rotated during this insertion of the instrument or subsequently. Inner rod  66  and microfistula tube  68  are advanced with outer tube  60  until the forward end  62  of outer tube  60  reaches subconjunctival space  52  (see FIG.  11 ). 
     Referring to FIG. 12, the inner rod  66  is then advanced within outer tube  60 , propelling microfistula tube  68  forward until microfistula tube  68  is adjacent to or extending marginally beyond the end  62  of outer tube  60 . Referring to FIG. 13, outer tube  60  is withdrawn from the immediate vicinity of the subconjunctival space  52 , with inner rod  66  held stationary, until microfistula tube  68  is entirely released from the outer tube  60 . The inner rod  66  prevents outer tube  60  from withdrawing the microfistula tube  68  during this step, after the completion of which the forward end  62  of outer tube  60  is in the anterior chamber  50 . 
     Finally, the outer tube  60  and inner rod  66  (see FIG. 14) are withdrawn from the body together, leaving the microfistula tube  68  at the implantation site. 
     Modifications within the spirit and scope of the invention may readily be effected by persons skilled in the art. For example, microfistula tubes may be adapted for use in other parts of the body where there is obstructed flow of fluid and/or high fluid pressure, with appropriate dimensions and corresponding surgical instrumentation. Possible other sites include the cranium (to treat raised intracranial pressure), shunting from the subarachnoid space to one of the head or neck veins, incorporating in the microfistula tube a material favouring the growth of venous or subarachnoid space endothelial cells, or—in the treatment of Menière&#39;s Disease—the invention may be used to shunt from endolymph to perilymph in the inner ear using a material favourable to the growth of subarachnoid endothelial cells. Further, such biological microfistula tubes may be useful in surgery upon the ureter or urethra, to overcome obstructions or strictures, using material favourable to the growth of urogenital epithelial cells. In addition, although the surgical instrument described above has been designed for the implantation of microfistula tubes, it may also be adapted for use for the implantation of other surgical or medical devices. Consequently, it is to be understood that this invention is not limited to the particular embodiments described by way of example hereinabove.