US20100121249A1 - Methods for reducing pressure in an organ - Google Patents

Abstract

Methods, system and apparatus for relieving pressure in an organ such as, but not limited to, the eye are disclosed. The method includes implanting a bioabsorbable channel into the selected area of the organ using a delivery apparatus.

Description

RELATED APPLICATIONS
• This application is a continuation of U.S. application Ser. No. 11/771,805, filed on Jun. 29, 2007, which claims the benefit of and priority to U.S. Provisional Patent Application No. 60/806,402, filed Jun. 30, 2006, both of which are hereby incorporated by reference in their entireties.
BACKGROUND
• The present disclosure generally relates to methods, systems and apparatus for relieving fluid pressure from an organ such as (but not limited to) the eye. More particularly, the present disclosure relates to methods and apparatus for treating glaucoma by relieving the pressure within the eye.
• Glaucoma is a disease of the eye that affects millions of people. Glaucoma is associated with an increase in intraocular pressure resulting either from a failure of the eye's drainage system to adequately remove aqueous humor from the anterior chamber of the eye or the overproduction of aqueous humor by the ciliary body. The build-up of aqueous humor and resulting intraocular pressure can cause irreversible damage to the optic nerve and the retina, which may potentially lead to irreversible retinal damage and blindness.
• Presently, glaucoma can be treated in a number of different ways, The most widely practiced treatment of glaucoma involves delivery of drugs such as beta-blockers or prostaglandins to the eye (typically in the form of eye drops) to either reduce the production of aqueous humor or increase the flow of aqueous humor from the anterior chamber of the eye. Glaucoma may also be treated by surgical intervention such as trabeculectomy. Trabeculectomy or similar surgical procedures involve creating conduits between the anterior chamber and the various structures involved in aqueous humor drainage such as Schlemm's canal, the sclera, and the subconjunctival space in order to provide a pathway for the aqueous humor to exit the anterior chamber.
• While these methods of treating glaucoma have been generally effective, they are not without their drawbacks. In the case of medicinal treatments of the eye, patient compliance is an issue because such treatments require regular (i.e., daily) intervention. With respect to surgical procedures such as a trabeculectomy, such procedures are very invasive and can cause irreversible changes to the eye. For example, trabeculectomy results in the permanent removal of a segment of the trabecular meshwork, inflammation and scarring in the quadrant of the eye where the surgery was performed, and the formation of a filtering bleb. Implantation of shunts such as the Molteno, Barveldt, or Ahmed shunts induce chronic foreign body reactions and the formation of a chronic subconjunctival bleb. In addition, such surgical treatment of glaucoma often requires long healing times and can result in certain complications such as infection, scarring, hypotony or cataracts.
• More recently, less invasive surgical treatments have been developed. These treatments do not require incision into the conjunctiva of the eye. One example of a less invasive surgical procedure is described in U.S. Pat. No. 6,544,249, the entire disclosure of which is hereby incorporated by reference. U.S. Pat. No. 6,544,249 discloses methods and apparatus for introducing a small bioabsorbable and biocompatible drainage canal, referred to therein as a microfistula tube into the portion of the eye that extends from the anterior chamber to the sub-conjunctival space. The procedure described in U.S. Pat. No. 6,544,249 does not require incision of the conjunctiva. Instead, introduction of the bioabsorbable microfistula tube is accomplished by an ab interno approach—through the cornea of the eye to the desired location (between the anterior chamber and the sub-conjunctival space.) U.S. Pat. No. 6,544,249 also generally describes a delivery apparatus for introducing and implanting the bioabsorbable microfistula tube.
• U.S. Pat. No. 6,007,511, the entire disclosure of which is incorporated herein by reference, likewise discloses less invasive methods and apparatus for treating glaucoma. As in the above-referenced U.S. Pat. No. 6,544,249, a bioabsorbable drainage tube is introduced into the area between the anterior chamber and the sub-conjunctival space to allow drainage of the aqueous humor from the anterior chamber of the eye. As in U.S. Pat. No. 6,544,249, incision of the conjunctiva is not required.
• These new procedures for treating glaucoma offer the promise of a long term cure of glaucoma without the shortcomings of medicinal treatments and without the risks associated with the known and presently practiced surgical procedures described above. Accordingly, it would be desirable to provide improved methods, systems, channels and delivery apparatus for treating glaucoma specifically and for treating other conditions where drainage of accumulated liquid is desired or required.
SUMMARY OF THE INVENTION
• The present disclosure sets forth improved methods and apparatus for carrying out channel implantation into an organ of the body such as the eye. It will be appreciated that the methods and apparatus described below may also find application in any treatment of a body organ requiring controlled drainage of a fluid from the organ. Nonetheless, the methods and apparatus for performing such treatment will be described relative to the eye and, more particularly, in the context of treating glaucoma.
• The present disclosure relates to an implantable, microfistula channel. The channel has a bioabsorbable body defining an interior flow path. The channel body is made of cross-linked bioabsorbable material such as gelatin and has an expandable outer diameter. The flow path has a diameter of between approximately 50 and 250 microns (μm).
• The present disclosure also relates to a method of making an implantable channel. The method includes providing a source of a bio-compatible gelatin solution and providing a generally cylindrical solid support. The support has a diameter of approximately 50 to 250 microns. The method includes contacting the outer surface of the support with the gelatin for a period of time sufficient to coat the support outer surface. A hollow gelatin tube is thus formed on the support. The formed hollow gelatin channel may be dried (cured) for a selected period of time and the formed gelatin tube may be subjected to a cross-linking treatment. The formed and cross-linked gelatin tube is removed from the support.
• The present disclosure also relates to an implantation apparatus for implanting a channel into an organ of a subject. The apparatus includes a reusuable portion that includes an apparatus housing. The housing has an open distal end, a proximal end and an interior chamber. The apparatus includes an arm subassembly within the housing that includes one or more movable arms adapted to engage a disposable needle assembly. The apparatus further includes one or more drivers coupled to said one or more moveable arms of the arm sub-assembly.
• The present disclosure further relates to systems for implanting a channel into an organ of a subject. The system includes a reusable portion adapted to receive a needle assembly and a disposable portion that includes a needle assembly. The needle assembly has a hollow needle terminating in a sharpened tip and a guidewire and a plunger disposed within the needle. The system includes a microprocessor-based controller including pre-programmed instructions for selective movement of at least the guidewire and the plunger.
• The present disclosure further relates to methods of implanting a bioabsorbable channel into an organ of a subject. In the methods described herein, an implantation apparatus including a hollow needle having a pointed distal end, a bioabsorbable channel within the needle assembly and a plunger proximally located relative to the channel is provided. The method includes the steps of introducing the pointed tip of the needle end assembly into the organ of a subject, advancing the needle to the desired area of implantation and actuating the plunger to advance the channel to the desired area of implantation. The method further includes removing the needle from the organ.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1, depicts, in general, a method for implanting a channel, showing in cross section, the distal end of an implantation apparatus;
• FIG. 2 is an enlarged, schematic view of the distal end of one embodiment of an implantation apparatus described herein;
• FIG. 3 is a perspective view of one embodiment of a handheld implantation apparatus with the door opened and a needle assembly installed therein;
• FIG. 4 is a top view of the apparatus ofFIG. 3 with front door removed;
• FIG. 5 is an exploded view of the system for implanting a channel including the apparatusFIG. 3;
• FIG. 6 is a perspective view of the distal end of the apparatus ofFIG. 3 with the needle assembly separated therefrom;
• FIG. 7 is an enlarged perspective view of the needle assembly ofFIG. 6;
• FIG. 8 is an exploded view of the needle assembly ofFIG. 7;
• FIG. 9(a)-(f) are schematic views of the implantation apparatus ofFIG. 3 showing the plunger, guidewire and needle arms in different positions during the positioning and/or implantation steps as they correspond to the positions of the plunger, guidewire, needle and channel within the eye;
• FIG. 10 is a perspective view of another embodiment of an implantation apparatus with the needle assembly installed therein;
• FIG. 11 is a perspective view of the implantation apparatus ofFIG. 10 and the disposable needle assembly in its extended state and separated therefrom;
• FIG. 12 is a side view of another embodiment of a handheld and manually operated implantation apparatus;
• FIG. 13 is a side view of still another embodiment of a handheld and manually operated implantation apparatus;
• FIG. 14 is an enlarged side view of the needle assembly of the apparatus ofFIG. 13;
• FIG. 15 is a perspective view of a syringe type, manually operated, handheld implantation apparatus;
• FIG. 16 is a schematic illustration of a method and apparatus for making a gelatin microfistula channel in the form of a tube;
• FIG. 17 is a schematic illustration an alternative embodiment of an apparatus for making a gelatin microfistula tube;
• FIG. 18 is a perspective view of an apparatus for making a plurality of microfistula gelatin tubes.
• FIG. 19 is a front view of a graduated needle inserted into the eye of a patient;
• FIG. 20 is a front view showing a transpupil channel insertion and placement;
• FIG. 21 is a schematic view showing an ipsilateral tangential channel insertion and placement;
• FIG. 22(a)-(d) depicts a series of steps showing an ipsilateral normal channel insertion and placement using a U-shaped or otherwise arcuate needle;
• FIG. 23 is a perspective view of a U-shaped needle of the type shown in the method of insertion and placement shown inFIGS. 22(a)-(d);
• FIG. 24 is a front view of the U-shaped needle ofFIG. 23;
• FIG. 25 is a side view of a needle having a bend at its distal end portion including the guidewire and channel inserted therein;
• FIG. 26 is a cross-sectional view of the needle, guidewire, plunger and channel of the needle distal end portion ofFIG. 25;
• FIG. 27 is a side view of the needle, the plunger or guidewire ofFIG. 25, wherein a portion of the plunger or guidewire facilitates bending of the same;
• FIG. 28 is a perspective view of a cylindrical channel including a tapered end;
• FIG. 29 is a perspective view of a cylindrical channel including retaining tabs for limiting migration of the channel;
• FIG. 30 is an end view of the tabbed channel ofFIG. 29;
• FIG. 31 is a perspective view of a cylindrical channel including centrally located barbs to limit migration of the implanted channel;
• FIG. 32 is a perspective view of a cylindrical channel including barbs located at one of the implanted channel to limit migration thereof;
• FIG. 33 shows the tabbed channel ofFIGS. 29-30 inserted within the eye of the patient.
DETAILED DESCRIPTION OF THE INVENTION
• Methods and apparatus for delivering and implanting bioabsorbable tubes or shunts are generally disclosed in U.S. Pat. Nos. 6,544,249 and 6,007,511, both of which have been previously incorporated by reference in their entireties. As set forth therein, and also with reference toFIG. 1, animplantation apparatus10 is used to deliver and implant a small micro-sized bioabsorbable tube i.e., themicrofistula tube26, to an area between theanterior chamber16 and thesub-conjunctival space18 of theeye12. The implantedmicrofistula tube26 provides a channel that continuously drains aqueous humor fromanterior chamber16 at a desired rate.Microfistula tube26 remains implanted in the eye, and eventually dissolves.
• FIG. 1 illustrates the distal (i.e., “working end”) end of the apparatus10 (including the microfistula tube26) as it approaches theeye12 as described in U.S. Pat. No. 6,544,249. Unlike current trabeculectomy procedures, in accordance with the method shown inFIG. 1,needle22housing microfistula tube26 approaches and enters the eye through cornea19 (ab intern) and not through the conjunctiva14 (ab externo). This prevents damage to the conjunctiva, improves healing time and reduces the risk of complications that may result from other surgical techniques of the prior art (e.g., trabeculectomy). As further shown and described in U.S. Pat. No. 6,544,249 and inFIG. 1,hollow needle20 is introduced through thecornea19 and is advanced across the anterior chamber16 (as depicted by the broken line) in what is sometimes referred to as a transpupil implant insertion.Channel26 is eventually implanted in the area spanning thesclera21,anterior chamber16 and the sub-conjunctival space18 (see also FIG. 8 of U.S. Pat. No. 6,544,249).
• The methods, systems, apparatus and channels described herein likewise utilize a hollow needle and a bioabsorbable channel delivered by the needle ab interno through thecornea19 or the surgical limbus17. As used herein, the term “channel” includes hollow microfistula tubes similar to the type generally described in U.S. Pat. No. 6,544,249 as well as other structures that include one or more flow paths therethrough.
• Turning now to a discussion of the methods, systems, apparatus and channels that embody the present invention, as generally shown inFIG. 2, the working end of implantation apparatus is provided as aneedle assembly20 that includes ahollow needle22 defining aninner chamber23 and terminating in a sharpened tip. Placed withininner chamber23 of thehollow needle22 is a cylindrical inner tube orplunger32 that is coaxial withneedle22. In the loaded and ready to use condition,channel26 is also placed or otherwise disposed within thehollow chamber23 ofneedle22 and is distally located relative toplunger32. Bothchannel26 andplunger32 may be placed over and supported byoptional guidewire28. As described in U.S. Pat. No. 6,544,249 and in this disclosure, through relative movement ofneedle22,plunger32, guidewire28, andchannel26 can be implanted intoeye12. As noted above, guidewire28 is optional and may be omitted where placement and advancement ofchannel26 does not require one.
• As will be described in greater detail below,channel26 may be delivered to and implanted within the desired location of the eye in any one of several different ways. The method of implantation (and system) may be fully automated, partially automated (and, thus, partially manual) or completely manual. For example, in a fully automated procedure,channel26 may be delivered by robotic implantation whereby a surgeon controls the advancement ofneedle22,plunger32,optional guidewire28 and, as a result,channel26 by remotely controlling a robot. In such fully automated, remotely controlled procedures, the surgeon's hands typically do not contactimplantation apparatus10 during the surgical procedure.
• Alternatively,channel26 may be delivered to the desired area of the eye with a “handheld” implantation apparatus, embodiments of which are shown inFIGS. 2-15 and described below. In one example of a handheld implantation apparatus, discussed in more detail below, movement of thechannel26,needle22, andplunger32 andoptional guidewire28 may be controlled remotely by an operator using a microprocessor-based device i.e., “controller,” whileimplantation apparatus10 is physically held by the surgeon. Insertion of the needle into the eye as well as certain repositioning or adjusting steps may be performed manually by the surgeon.
• In the case of fully manual apparatus and methods, which are also discussed below and shown inFIGS. 12-15, all of the positioning, repositioning, adjusting and implantation steps are performed manually by the surgeon.
• One example of animplantation apparatus10 and system embodying the present invention is shown inFIGS. 3-9. Althoughapparatus10 shown inFIGS. 3-9 is preferably a handheld type implantation apparatus where relative movement of the needle, optional guidewire and plunger is accomplished automatically by pre-programmed instructions in a microprocessor-based controller and at least some of the steps may be manually performed by the surgeon,apparatus10 can also be used in a fully automated environment. In any event,implantation apparatus10 shown inFIG. 3 includes areusable portion30 and a disposable portion embodied inneedle assembly20. As will be discussed in greater detail below,needle assembly20 is separately provided and is received byarm sub-assembly55 ofimplantation apparatus30.
• As shown inFIG. 3,implantation apparatus10 includes a generally cylindrical body orhousing34, although as will be appreciated from other embodiments disclosed herein, the body shape ofhousing34 is not critical. However, ifapparatus10 is to be held by the surgeon (i.e., a handheld apparatus) the shape ofhousing34 should be such that is ergonomical, allowing for comfortable grasping by the surgeon.Housing34 is closed at its proximal end byend cap38 and has anopening39 at its distal end through which at least a portion ofneedle assembly20 extends.Door36 provides access to the interior ofhousing34 allowing for easy insertion and removal ofneedle assembly20. Locking means such asslide lock37 may be provided to securedoor36 to (and releasedoor36 from)housing34.Door36 may be secured tohousing34 by ahinge41 allowing the door to swing open when it is unlocked. In an alternative embodiment,door36 may be slidably attached tohousing34 and access to the interior ofhousing34 may be achieved by slidingdoor36 toward the proximal end of thehousing34. Of course, it will be appreciated that other ways of providing access to the interior of theimplantation apparatus10 are also possible.
• Housing34 anddoor36 may be made of any material that is suitable for use in medical devices. For example,housing34 may be made of a lightweight aluminum or, more preferably, a biocompatible plastic material. Examples of such suitable plastic materials include polycarbonate and other polymeric resins such as Delrin.®. and Ultem.®. Similarly,door36 may be made of a plastic material such as the above-described materials including polymers and polymer resins such as polycarbonate, Delrin.®. and Ultem.®. In a preferred embodiment, door may be substantially translucent or transparent.
• Re-usable portion30 ofimplantation apparatus10 houses the components required to effect movement of theneedle assembly20 components during the implantation procedure. As shown inFIGS. 3-6,implantation apparatus10 houses a plurality of moveable arms, collectively referred to herein as thearm sub-assembly55, which is adapted to receiveneedle assembly20.Arms54,58 and62 are axially moveable between the proximal and distal ends ofapparatus10 and are coupled to lead screws52(a)-(c) at their distal ends which, in turn, are coupled to one ormore drivers44,46,48. In the embodiment shown inFIGS. 3-6, drivers are preferably a plurality of gear orstepper motors44,46 and48. Alternatively, arms may be driven pneumatically or otherwise.
• With respect to the embodiments ofFIGS. 3-6,motors44,46 and48 are housed near the proximal end ofimplantation apparatus10.Motors44,46 and48 may be stacked or bundled in parallel in the manner shown inFIG. 5 and held in place byfront motor mount50 andrear motor mount40.
• As indicated above, each of themotors44,46 and48 (or other drivers) is coupled to one of the lead screws52(a)-(c), which, in turn, are coupled tomovable arms54,58 and62 ofarm sub-assembly55. For example, with specific reference to the embodiment ofFIGS. 3-6, lead screw50(a) is coupled toguidewire arm54; lead screw50(b) is coupled toplunger arm58; and lead screw50(c) is coupled toneedle arm62.Motors44,46 and48 may be selectively and independently activated by switches on theapparatus10 itself or as schematically shown inFIG. 5 as described, may be coupled to aremote controller8 of the system. In one embodiment,apparatus10 includes printed circuit board7 which establishes an electrical connection betweenmotors44,46 and48 andcontroller8.Controller8 may include a control box that supplies power and pre-programmed positioning instructions to theimplantation apparatus30 generally andmotors44,46 and48, specifically. Movements of thevarious arms54,58 and62 can be initiated by the surgeon via a foot switch or other type ofremote control6.
• As shown in the Figures,arms54,58 and62 are preferably of varying axial lengths. Each of thearms54,58 and62 includes a slot for receiving a portion of the needle assembly20 (described below.) Thus,guidewire arm54 includes aguidewire hub slot57;plunger arm58 includes aplunger hub slot59 andneedle arm62 includes aneedle hub slot63.
• In a preferred embodiment, each of thearms54,58 and62 includes at its distal and/or proximal ends a portion having an enlarged cross-section. The distal “blocks”54(a),58(a) and62(a) provide abutment surfaces which limit axial movement of the respective arms. As will be seen from the discussion of the implantation method, the distal blocks which also defineslots59,62 and63 limit movement of the particular arms, thereby ensuring that the guidewire, plunger andchannel26 do not move beyond a pre-determined distance. Similarly,wall65 ofhousing34 limits movement ofneedle arm62, likewise ensuring that the needle does not penetrate the eye beyond a desired distance. Proximal blocks58(a),58(b) and58(c) (not shown) likewise provide an abutment surfaces for contacting fixedcollars53 on lead screws52(a)-(c). Contact between the surfaces of blocks58(a),58(b) and58(c) andrespective collars53 provides an indication that arms ofarm subassembly55 are in their rearmost or “hard stop” position, discussed below. Blocks58(a)-(c) also include internal threaded nuts through which lead screws50(a)-(c) travel.
• As further seen inFIGS. 3-6,implantation apparatus10 includes aguide block66 attached toneedle arm62.Guide block66 defines two partially enclosed apertures for slidably retainingguidewire arm54 andplunger arm58.Guide block66 prevents rotation or other undesired dislocation ofguidewire arm54 andplunger arm58 and maintains these components in an axially aligned orientation.Guide block66 also serves as a stop that limits movement ofarms54 and58.
• As noted above,arm sub-assembly55 is adapted to receiveneedle assembly20. Needle assembly, shown inFIGS. 7 and 8 is itself made of a plurality of separate, and co-axially assembled parts. Co-axial assembly of these constituent parts allows for relative axial movement ofoptional guidewire28,needle20 andplunger32. As shown inFIGS. 7 and 8, in one embodiment, needle assembly includes aguidewire hub72. In the embodiment shown,guidewire hub72 includes adistal cylinder82 and aproximal block84.Guidewire28 extends from thecylinder82 and is received withinplunger hub68 which likewise includes a distal hollow cylinder andproximal block90.Plunger tube32 extends fromplunger cylinder88 and when brought together withguidewire hub72 surrounds guidewire86 along most of its length. Both guidewire28 and plunger tube92 are then received byneedle hub96. Ahollow needle22 attached toneedle mount23 is mounted onneedle hub96.Hollow needle22 has an inner diameter sufficient to receive the assembled co-axial guidewire86 and plunger92. Of course, it will be appreciated that in certain embodiments, a guidewire may not be required and thatneedle assembly20 may include a plunger and needle only.
• As best shown inFIG. 6,needle assembly20 is adapted for placement withinarm assembly55. More specifically,guidewire block84,plunger block90 andneedle block94 ofneedle assembly20 are received by theslots57,59 and63, respectively, ofarm sub-assembly55. Each ofblocks84,90 and94 may include anupstanding pin85,91 and95 (respectively).Pins85,91 and95 are of a height sufficient so as to almost contact the inner surface of door36 (when closed). Providing pins of sufficient height keeps needle assembly from becoming dislodged fromsub-assembly55 in the event thatapparatus10 is rotated by the surgeon. As shown inFIGS. 7 and 8,hollow needle22 is preferably protected prior to use byremovable needle cap80.
• Another embodiment of a handheld implantation apparatus is shown inFIGS. 10-11. As in the embodiment described above, hand-heldimplantation apparatus10 ofFIG. 10 includes areusable portion30 that includes handle180,movable block182 andslider assembly214. As with the embodiment ofFIGS. 3-9 above,needle assembly20, itself includes several different components that can be preassembled (as shown inFIG. 10) and are axially movable relative to one another. For example, in the embodiment shown inFIG. 10,needle assembly20 includesplunger32,needle adapter184 andguidewire holder24.Plunger32 has a hollow cylindrical body which has an open distal end and an open proximal end. Open proximal end ofplunger32 receivesguidewire28 andguidewire holder24.
• As further shown inFIG. 10, distal end ofplunger32 is received byhollow needle adapter184 andneedle adapter184 receivesdisposable needle22.Needle22 includes a distal piercing end and ahub188 which is fitted overneedle adapter184. Once assembled, guidewire extends fromguidewire holder24 throughplunger32, throughneedle adapter184 andneedle22. In the embodiments ofFIG. 10,channel26 is typically placed onguidewire28 near the distal end thereof withinhollow needle22.
• Needle assembly20 is mounted onto reusablehandheld portion30. More particularly, as shown inFIG. 3, needle assembly is fitted intoslots192,194 and196 ofimplantation apparatus30. For example,collar198 ofguidewire holder24 is received withinslot192,collar200 ofintermediate tube32 is positioned withinslot194, andcollar202 ofneedle adapter34 is received withinslot196.
• Implantation apparatus10 includes ahandle180. Handle180 preferably includesgroove206 along the side wall for easy gripping by the surgeon. As shown inFIGS. 10 and 11, handle204 supportsmovable slider block182.Block182 includes aslide210 that fits within a central slot ofhandle180. During use ofimplantation apparatus10, block182 may move axially within the slot ofhandle180.Movable slider block182 may also include a slot212 (seeFIG. 10) which receivesplunger block assembly214. As shown in the figures,plunger block214 may be slidable withinblock182.Plunger block assembly214 includes forwardly extendingarms216 which defines at its distal end a slot192 (in which collar25 ofguidewire holder24 is received). Plunger block assembly also includesguidewire slider block218 that is movable withinslot219 defined byarms216.Guidewire slider block218 is coupled to motor230 (discussed below) byscrew220.
• Reusable portion30 ofhandheld implantation apparatus10 generally depicted inFIGS. 10 and 11 may further include drivers for selectively actuating movement of the component parts ofneedle assembly20, such asneedle22, guidewire28,plunger32, andchannel26. As in the embodiment ofFIGS. 3-9, in the embodiment ofFIGS. 10 and 11, the drivers for selectively moving these and other components may be one or more motors, such as gear or stepper motors. Motors230 may be selectively activated to move the desired component ofapparatus10. In one non-limiting example shown inFIGS. 10 and 11, a plurality of stepper motors230(a), (b) and (c) are carried by handheld implantation apparatus. Motors230(a)-(c) may be selectively activated by switches on the apparatus itself, remote hand-operated switches, a foot-operated controller and/or an automatically controlled via a preprogrammed controller (i.e., computer)8.
• Regardless of the means of control, in the example shown inFIGS. 10 and 11, motor230(a) causes movement ofguidewire slider block218. Movement ofguidewire slider block218 which holds collar25 ofguidewire holder24 results in selective back and forth movement ofguidewire28. Motor230(b) movesarm216 withinslot212 which holdscollar200 ofplunger32, allowing for back and forth movement ofplunger32. Finally, motor230(c) drivesblock182 including theentire needle assembly20 further includingblock214 and its associated components.
• Of course, as described in relation to the embodiment ofFIGS. 10-11, means for advancing or moving the operative components ofhandheld implantation apparatus30 ofFIGS. 11-12 need not be electrical and/or motor driven. Other embodiments of ahandheld apparatus10 that include other ways for actuating movement of the individual components may also be employed. For example, as shown inFIGS. 12-15, in alternative embodiments of a handheld implantation apparatus, theapparatus10 may include mechanical means for selectively advancing the component parts of the needle assembly and the handheld implantation apparatus.
• Turning toFIG. 12,implantation apparatus110 includes a reusablehandheld portion112 that receives adisposable needle assembly114.Implantation apparatus110 includes athumbwheel116 placed on and movable along threadedscrew118. Attached tothumbwheel116 is asyringe body120. Distal end ofsyringe120 receivesneedle assembly122.Implantation apparatus110 includes a conduit that extends through thehandle113 and is adapted for receivingguidewire28.
• Placement ofchannel26 ontoguidewire28 may be achieved by turningthumbwheel116 in a first direction to retractneedle assembly122 andhollow needle124, thereby revealing the distal end ofguidewire28 andplunger tube32. At that point,channel26 is placed (typically manually) onguidewire28 so that the proximal end thereof (the end opposite the leading end of channel26) of channel comes into contact with the distal end ofplunger32.Thumbwheel116 is then turned in an opposite direction to the first direction to slideneedle124 overplunger tube32 andchannel26.
• Channel26 is now ready for implantation. During the implantation process,needle124 is inserted into the eye and, more specifically, thecornea19 or surgical limbus17 of the eye in the manner described above and in U.S. Pat. No. 6,544,249.Needle124 is advanced acrossanterior chamber16 and into thesub-conjunctival space18, stopping short of theconjunctiva14.Thumbwheel116 is then rotated again in the first direction to retractneedle124 and thereby exposechannel26. Once in place, guidewire is retracted, releasingmicrofistula26 fromguidewire28. Retraction of guidewire may be achieved manually by a simple pulling ofguidewire28 at the proximal end ofapparatus110. Oncechannel26 is in its final position,needle124 is removed.
• FIGS. 13 and 14 illustrate another embodiment of ahandheld implantation apparatus130 that likewise utilizes mechanical means for advancing and/or selectively moving the component parts of the needle assembly and/orapparatus130. As in the embodiment ofFIG. 12, handheld implantation apparatus relies on mechanically driving the component parts. As shown inFIG. 13,implantation apparatus130 includeshandle portion132 with aneedle assembly134 attached to the distal end ofbody132. Athumbwheel136 is rotatable and coupled to an internal screw (not shown). Internal screw is attached toarms138 which graspflange140 ofneedle assembly134, such that turning ofthumbscrew136 effects axial movement ofneedle assembly134.
• In contrast to the embodiment ofFIG. 12,implantation apparatus130 may further include additional means for controlling movement of other components of the implantation apparatus. For example, in the embodiment ofFIG. 13, asecond thumbwheel142 is mechanically coupled toguidewire28. A rotation ofthumbwheel142 allows for retraction ofguidewire28 after implantation ofchannel28.
• FIG. 14 provides an enlarged view ofneedle assembly134 shown inFIG. 13. As seen inFIG. 14, anassembly retainer146 is provided.Assembly retainer146 is affixed to theneedle assembly134 during shipment to prevent movement ofguidewire28 and control tube. Retainer is removed prior to insertion of theneedle assembly134 onto thehandle132 ofapparatus130.
• FIG. 15 shows another embodiment of an implantation apparatus. Theimplantation apparatus150 ofFIG. 8 includes ahandle152, a movable orslidable syringe portion154 and atrigger156 for actuating movement ofslidable syringe124.Implantation apparatus150 further includes an attachable needle assembly158 (with needle22) at the distal end ofsyringe154. As shown inFIG. 15, guidewire28 extends throughimplantation apparatus150 in similar fashion to the apparatus ofFIG. 12.Guidewire28 extends throughbarrel154 and carries atube32 near its distal end.Barrel154 is preferably filled with gas (e.g., air, CO.sub.2, nitrogen or liquid (e.g., water, trypan blue, saline or a viscoelastic solution).
• For placement ofchannel26 ontoguidewire28,trigger156 is pulled, resulting in rearward movement ofsyringe154 andneedle22. Rearward movement ofneedle22 exposes guidewire28 and allows for placement ofchannel26 onto guidewire. Release of thetrigger158 advances needle22 to coverguidewire28 andchannel26. As in the previous embodiments,needle22 piercescornea19 or surgical limbus17, and is advanced throughanterior chamber16 to the desired location of the eye (i.e. the area between thesub-conjunctival space18 and the anterior chamber).Trigger156 is once again pulled to moveneedle assembly158 in a rearward direction thereby exposingchannel26 carried byguidewire28. Once the surgeon has determined that thechannel26 is in the desired location, guidewire28 is retracted, thereby releasingchannel26. As shown inFIG. 15, retraction ofguidewire28 may be performed manually, as in the embodiment ofFIG. 12, by simply pullingguidewire28. Alternatively, mechanical means for moving guidewire, as in the examples ofFIGS. 12 and 13, may also be provided.
• Although selective movement ofguidewire28, needle assembly,plunger32 orguidewire holder24 with thechannel26 using electrical, mechanical or even some manual means have been described, other means for actuating movement of these components may also be used instead of or in addition to such means. For example, movement of the various component parts may be achieved by pneumatic control or fluidic control.
• The method of implantingchannel26 using implantation apparatus will now be described. The method will be described with particular reference to the embodiment ofFIGS. 3-9, although many of the steps described may also be employed using other embodiments of the implantation apparatus. In addition, depending on the type of apparatus and type of channel used, there may be variations to some of the method steps. For example, in some embodiments, a guidewire may be omitted. In addition, the advancement and retraction steps of the parts of needle assembly may be continuous or incremental. Regardless of the apparatus used, the sequence of steps, distances traveled and continuous or incremental movement, the ultimate location ofchannel26 is substantially the same using any of the methods, systems and apparatus described herein.
• At the outset, it will be appreciated that the implantation ofchannel26 requires precise placement of thechannel26 in the correct location within the eye. Moreover, it will also be appreciated that the distances traveled by thechannel26,plunger32, guidewire28 andneedle22 are typically measured in millimeters. Such precision may be difficult for even the most skilled surgeon to achieve by manual manipulation (due to natural hand tremors in humans). Accordingly, in embodiments other than the manual hand-held implanters inFIGS. 12-15, many of the actual implantation steps are preferably carried out under the automatic control of an external, preprogrammedcontroller8. While the initial eye entry steps and some repositioning steps may be performed manually by the surgeon, steps related to the release and location ofchannel26 may be automatically controlled.
• In a first step, preferably performed during factory assembly,channel26 is loaded intoneedle assembly20. During loading, the distal tip of guidewire preferably extends slightly beyond the beveled tip ofhollow needle22.Channel26 may be manually placed onguidewire28 until proximal end ofchannel26 contacts the distal end ofplunger32.Guidewire28, withchannel26 placed thereon is then retracted intohollow needle22.
• Prior to loadingneedle assembly20 intoapparatus30, pre-positioning of arm-subassembly may be desired or required. Thus, in a first step, all motors are activated to retractguidewire arm54,plunger arm58 andneedle arm62 to a proximal most position such that the proximal end surfaces of the arms abut againstcollars53. This “hard stop” position is shown schematically inFIG. 9a. The operator may then prepareimplantation apparatus30 for loading of needle assembly by activating each motor and advancing eacharm assembly55 to a “home” position and shown inFIG. 9(b). As will be seen inFIG. 9(b) movement ofneedle arm62 is restricted bywall70 ofapparatus30. With the motors properly aligned in the “home” position, needle assembly is installed by inserting guidewire hub block86 intoguidewire hub slot57;plunger hub block90 intoplunger hub slot59 and needle hub block intoslot63. Withneedle assembly20 properly installed, the surgeon may begin the procedure by inserting the end distal tip ofhollow needle22 into the eye. As shown inFIG. 1 and as previously described, the surgeon inserts thehollow needle22 into the anterior chamber via the cornea or surgical limbus of the eye and advances it either manually (or under automatic control) to a location short of the final implantation site. Alternatively, the surgeon may first make an incision in the eye and insertneedle22 through the incision. Once theneedle22 has been properly inserted and placed, the program may be activated to commence automatic implantation ofchannel26. In a first implantation step, simultaneously motors)44 and46 are activated to advanceguidewire arm54 and plunger are58 as shown inFIG. 9(c) which thereby advanceschannel26 forward into the subconjunctival space of the eye, as generally depicted inFIG. 9(c). For example, in one embodiment,plunger32 and guidewire28 are advanced approximately a total of 2 millimeters. Preferably, the rate of placement of channel is carefully controlled because it allows the channel to absorb fluid from the surrounding tissue thereby causing it to swell and to provide better anchoring in the tissue. Rapid advancement or placement ofmicrofistula channel26 may not allowtube26 to adequately swell which can possibly result in unwanted migration ofchannel26 after implantation. In one embodiment, the rate of placement may be between approximately 0.25-0.65 mm/sec.
• After the advancement of the plunger and guidewire described above,motor48 is activated andneedle arm62 is moved in a rearward direction such thatneedle22 is withdrawn from its position shown inFIG. 9(c) to the position shown inFIG. 9(d). Withdrawal ofneedle22 should preferably expose the entire length ofchannel26, and, in addition, the distal end of the plunger, thereby allowing the surgeon to visualize the final position of the proximal edge of the channel. In one embodiment, the distance that hollowneedle22 is withdrawn is approximately 4.2 millimeters. At this point, the program prompts (e.g., audibly) the surgeon to visually view the location ofchannel26 and determine if it is correctly placed. The surgeon can manually make any adjustments to a desired position by moving the implanter forward or backward. The automatic system may be programmed to allow the surgeon sufficient time to make any further manual adjustments and may require the surgeon to press the foot or other switch or otherwise effect movement to continue delivery of the channel. After a selected period of time, the automated program preferably resumes control of implantation procedure by activatingmotor guidewire motor44, to retractguidewire arm54 and thus withdrawguidewire28 as shown inFIG. 9(e). Removal of the guidewire preferably occurs in one single step as shown inFIG. 9(e). Finally, the system will then preferably alert the surgeon that the procedure is now complete and theneedle22 may be withdrawn (manually or automatically) from the eye as shown inFIG. 9(f).
• From the preceding discussion, it will be appreciated that bioabsorbable microfistula channel is implanted by directing the needle across the anterior chamber, entering the trabecular meshwork (preferably between Schwalbe's Line and the Scleral spur), and directing the needle through the sclera until the distal tip of the needle is visible in the subconjunctival space. The length of the channel through the sclera should be approximately 2-4 mm. Once the surgeon has placed the needle in this location, he may actuate the implanter to begin the release steps. The channel is released and the needle is withdrawn such that approximately 1-2 mm of the channel resides in the sub conjunctival space, approximately 2-4 mm resides in the scleral channel, and approximately 1-2 mm resides in the anterior chamber. Once the channel is released, the surgeon removesapparatus needle20.
• Proper positioning of thebioabsorbable channel26 should be carefully controlled for at least the following reasons. If the surgical procedure results in the formation of a bleb, the more posterior the bleb is located, the fewer complications can be expected. Additionally, the bleb interferes less with eyelid motion and is generally more comfortable for the patient. Second, a longer scleral channel provides more surface contact between the channel and the tissue providing better anchoring. Third, the location of the channel may play a role in stimulating the formation of active drainage structures such as veins or lymph vessels. Finally, the location of the channel should be such so as to avoid other anatomical structures such as the ciliary body, iris, and cornea. Trauma to these structures could cause bleeding and other complications for the patient. Additionally, if the bleb is shallow in height and diffuse in surface area, it provides better drainage and less mechanical interference with the patient's eye. Tall, anteriorly located blebs are more susceptible to complications such as conjunctival erosions or blebitis which require further intervention by the surgeon.
• The ab interno approach provides better placement than the ab externo approach because it provides the surgeon better visibility for entering the eye. If directing the needle from an ab externo approach, it is often very difficult for the surgeon to direct the needle to the trabecular meshwork (between Schwalbe's line and the scleral spur) without damaging the cornea, iris, or ciliary body.
• In an alternative method of implantation, it is possible to direct the needle from the trabecular meshwork into the suprachoroidal space (instead of the subconjunctival space) and provide pressure relief by connecting these two spaces. The suprachoroidal space also called supracilliary space has been shown to be at a pressure of a few mmHg below the pressure in the anterior chamber.
• Common to all of the embodiments of handheld implantation apparatus are a needle assembly including a hollow needle. In a preferred embodiment,hollow needle22 may be any needle suitable for use in medical procedures. As such,needle22 is made of a hard and rigid material such as stainless steel with a beveled sharpened distal tip.Needle22 is bonded, welded, overmolded, or otherwise attached to theneedle mount23 and/or hub that is adapted for placement onto the distal end of a needle assembly. Theneedle22 is disposable and intended for one time use.
• Hollow needle22 and indeed, the entire needle assembly may be sterilized by known sterilization techniques such as autoclaving, ethelyne oxide, plasma, electron beam, or gamma radiation sterilization. In a preferred embodiment,needle22 is a 25 gauge thin walled needle that is commercially available from Terumo Medical Corp., Elkton, Md. 21921. The inside diameter ofhollow needle22 must be sufficient to accommodateoptional guidewire28,channel26 andplunger tube32, with an inner diameter of 200-400 μm being preferred. The usable length ofneedle22 may be anywhere between 20-30 mm, although a length of approximately 22 mm is typical and preferred. Preferably,needle22 may include markings orgraduations27 near the distal tip as shown inFIG. 19. A graduated needle may be particularly useful to a surgeon inasmuch as much of the needle within the eye is not visible to the surgeon. Typically, the only visible portion ofneedle22 is the portion within the anterior chamber. Accordingly,graduations27 uniformly spaced along the needle shaft assist the surgeon in determining how far to advance the needle in order to placechannel26 in the desired location. In one embodiment, the graduations may be applied using laser marks, ink, paint or engraving and are typically spaced 0.1 to 1.0 mm apart.
• While a straight hollow needle of the type typically used in medial procedures is generally preferred, in an alternative to the needle shown in theFIGS. 3-15 and described above,needle22 may be rigid and have a distal portion that is arcute as shown inFIGS. 22-24. As shown inFIGS. 22(a)-(d) andFIGS. 23-24 arcuate needle may be preferably U-shaped or substantially U-shaped. With an “arcuate” needle, instead of pushing the needle into the patient's eye, the surgeon may orient the needle to “pull” the needle into the patient's eye. As shown inFIGS. 23-24, the distal portion of theneedle22 terminating in the beveled tip, identified byreference number96 is preferably disposed obliquely relative to the longitudinal axis ofneedle shaft98 as seen inFIG. 24.
• Providing a piercingend96 that is bent away from the plane ofneedle shaft98 can facilitate manipulation and rotation ofneedle22 during implantation oftube26. It may also provide the surgeon with greater flexibility in terms of selecting the corneal entry site and the ultimate final position ofchannel26. This is perhaps best seen with reference toFIGS. 20,21 and22(a)-(d).
• For example,FIG. 20 depicts a transpupil implantation delivery generally described in U.S. Pat. No. 6,544,249 as shown inFIG. 1. While the approach is satisfactory, it does require the needle to cross the visual axis. In the event of a surgical error that causes damage to the cornea or lens, corrective surgery may be required.
• FIG. 21 depicts an alternative method of delivery referred to as an ipsilateral tangential delivery ofchannel26. In the ipsilateral tangential delivery method, the straight needle is directed tangentially to thepupil100 border and the surgical limbus. This type of implant delivery allows the channel to be delivered to a greater circumference of the eye and has the advantage of avoiding the visual axis. Avoiding the visual axis reduces the risk of complications to thecornea19 and lens through contact during surgery. Ipsilateral tangential delivery is a modification of the transpupil implant location generally described in U.S. Pat. No. 6,544,249, previously incorporated by reference.
• Although the transpupil implant delivery and/or the ipsilateral tangential delivery, if performed correctly, are acceptable methods of deliveringchannel26, they do somewhat limit the location of the corneal entry site due to interference with the nose and eye orbit bones. In that regard, an arcuate needle of the type described above and shown in FIGS.22(a)-(d) andFIGS. 23-24 may provide greater flexibility to the surgeon. With an arcuate needle,channel26 may be placed anywhere around the 360.degree. circumference of the eye, including the temporal quadrants which would not be otherwise accessible for the reasons discussed above.
• A further advantage of the arcuate needle and the delivery implant method associated therewith is thatmicrofistula channel26 can be delivered without crossing the lens i.e., visual axis, thereby reducing the risk of complications. An arcuate needle design may also allow the surgery to be done in patients with abnormal anatomy or who have previously undergone surgery.
• In accordance with delivering amicrofistula channel26 using the U-shapedhollow needle20 ofFIGS. 23 and 24, as noted above, instead of pushing the needle into the patient's eye, the surgeon orients the needle to “pull”needle22 into the patient's eye. Thus, as shown inFIG. 22(a), the pointed tip ofhollow needle22 is inserted at the desired corneal entry point and pulled in the direction of the arrow. Once the portion ofneedle22 that contains thechannel26 is in the patient's eye, the surgeon rotates the needle and directs theneedle22 toward the target within the angle of the anterior chamber. After adjustingneedle22 to the proper position, the surgeon again pulls theneedle22 in the direction of the arrow ofFIG. 22(b) so that the needle is directed through the trabecular mesh work and sclera. The particular advancement and delivery steps described previously are then performed to place thechannel26 in the desired location and withdraw the guidewire plunger and needle from the eye. Of course, retraction and other movements of the needle may be automatically controlled in the manner described above and as shown inFIG. 9.
• In a further embodiment, ahollow needle22 that is bent (but not necessarily in a U-shape as described above), may be provided. A needle of this type is shown inFIGS. 25-27. As with the “arcuate” or U-shaped needles discussed above, a simple bend in the distal portion ofneedle22 can likewise avoid interference from the patient's facial features. A bend that creates an angle α of between 900°-180° may be preferred. Providing aneedle22 with a bend is also ergonomically desirable in that it improves the position of the surgeon's hands during surgery. For example, by providing a bend in the distal portion ofneedle22, a surgeon may rest and stabilize his hands on the patient's forehead or other support while making the initial corneal entry and carrying out the later implantation steps. Providing a bend in the distal portion ofneedle22 is not merely an alternative to the U-shaped needle ofFIGS. 23 and 24. In fact, both features i.e., a needle with an arcuate distal portion and further having a bend near the distal tip may be employed together in theneedle22.
• Whether the needle is U-shaped or bent at an angle .alpha. shown inFIG. 25, the component parts ofneedle22 must likewise be susceptible to bending. Accordingly, instead of arigid plunger32 and guidewire28, both the plunger and guidewire may be, in part, bendable or be made of a material that is bendable, yet provides adequate support and has adequate strength. In one example, theplunger32 may be made of a tightly wound coil such as but limited to a spring or coil. Alternatively, at least a portion ofguidewire28 orplunger32 may be made of a flexible plastic material including a polymeric material, examples of which include polyimide, PEEK, Pebax or Teflon. Other bendable, flexible materials may also be used. Similarly, guidewire28 may be made of any of the above-described materials or a material such as nitinol which has shape memory characteristics. The entire plunger orguidewire28 may be made of the flexible materials described above or, as shown inFIG. 27 only a portion of theguidewire28 orplunger tube32 may be made of the selected material or be otherwise bendable.
• Typically, however, guidewire28 is preferably a narrow gauge wire made of a suitable rigid material. A preferred material is tungsten or stainless steel, although other non-metallic materials may also be used. In a preferred embodiment, guidewire28 is solid with an outside diameter of approximately 50-200 (ideally 125) microns. Whereguidewire28 is made of tungsten, it may be coated with a Teflon, polymeric, or other plastic material to reduce friction and assist in movement ofchannel26 alongguidewire28 during implantation.
• Channels26 useful in the present invention, are preferably made of a biocompatible and preferably bioabsorbable material. The materials preferably have a selected rigidity, a selected stiffness and a selected ability to swell (during manufacture and/or after implantation) in order to provide for secure implantation of the channel in the desired section of the eye. Selecting a material that is capable of a controlled swelling is also desirable. By controlled swelling, it is meant that the swellable material is such that the outer diameter of the channel expands (increases) without decreasing the inner diameter. The inner diameter may increase or remain substantially the same. The materials and methods for making channels described below provide such controlled swelling. By sufficient biocompatibility, it is meant that the material selected should be one that avoids moderate to severe inflammatory or immune reactions or scarring in the eye. The bioabsorbability is such that the channel is capable of being absorbed by the body after it has been implanted for a period of anywhere between 30 days and 2 years and, more preferably, several months such as 4-7 months.
• In one embodiment, the material selected for the channels is preferably a gelatin or other similar material. In a preferred embodiment, the gelatin used for making the channel is known as gelatin Type B from bovine skin. A preferred gelatin is PB Leiner gelatin from bovine skin, Type B,225 Bloom, USP. Another material that may be used in the making of the channels is a gelatin Type A from porcine skin also available from Sigma Chemical. Such gelatin is available is available from Sigma Chemical Company of St. Louis, Mo. under Code G-9382. Still other suitable gelatins include bovine bone gelatin, porcine bone gelatin and human-derived gelatins. In addition to gelatins, microfistula channel may be made of hydroxypropyl methycellulose (HPMC), collagen, polylactic acid, polylglycolic acid, hyaluronic acid and glycosaminoglycans.
• In accordance with the present invention, gelatin channels are preferably cross-linked. Cross-linking increases the inter- and intramolecular binding of the gelatin substrate. Any means for cross-linking the gelatin may be used. In a preferred embodiment, the formed gelatin channels are treated with a solution of a cross-linking agent such as, but not limited to, glutaraldehyde. Other suitable compounds for cross-linking include 1-ethyl-3-[3-(dimethyamino)propyl]carbodiimide (EDC). Cross-linking by radiation, such as gamma or electron beam (e-beam) may be alternatively employed.
• In one embodiment, the gelatin channels are contacted with a solution of approximately 25% glutaraldehyde for a selected period of time. One suitable form of glutaraldehyde is a grade 1G5882 glutaraldehyde available from Sigma Aldridge Company of Germany, although other glutaraldehyde solutions may also be used. The pH of the glutaraldehyde solution should preferably be in the range of 7 to 7.8 and, more preferably, 7.35-7.44 and typically approximately 7.4.+−0.0.01. If necessary, the pH may be adjusted by adding a suitable amount of a base such as sodium hydroxide as needed.
• Channels used in the present invention are generally cylindrically shaped having an outside cylindrical wall and, in one embodiment, a hollow interior. The channels preferably have an inside diameter of approximately 50-250 microns and, more preferably, an inside diameter and us, a flow path diameter of approximately 150 to 230 microns. The outside diameter of the channels may be approximately 190-300 with a minimum wall thickness of 30-70 microns for stiffness.
• As shown inFIG. 28, one end oftube26 may be slightly tapered to limit or prevent migration oftube26 after it has been implanted. Other means for limiting migration are also shown inFIGS. 29-33. For example,channel26 may includeexpandable tab150 alongouter surface152 oftube26. As shown inFIG. 29, prior to deployment and introduction of tube into the patient's eye,tabs150 are rolled or otherwise pressed againstsurface152.Tabs150 may also be features that are cut out of the outer surface of channel26 (i.e., not separately applied). Upon contact with an aqueous environment,tabs150 are deployed. Specifically, contact with an aqueous environment causestabs150 to expand as shown inFIG. 30 and, thereby, create an obstruction which limits or prevents migration oftube26.Tube26 may include a plurality of tabs, typically but not limited to 1-4, and may be located nearer the subconjuctival side, the anterior chamber or both, as shown inFIG. 33. Other means for limiting or preventing migration includebarbs158 placed along the length oftube26 as shown inFIGS. 31-32 and also disclosed in U.S. Pat. Nos. 6,544,249 and 6,007,511, previously incorporated by reference.
• The length of the channel may be any length sufficient to provide a passageway or canal between the anterior chamber and the subconjunctival space. Typically, the length of the channel is between approximately 2 to 8 millimeters with a total length of approximately 6 millimeters, in most cases being preferred. The inner diameter and/or length oftube26 can be varied in order to regulate the flow rate throughchannel26. A preferred flow rate is approximately 1-3 microliters per minute, with a flow rate of approximately 2 microliters being more preferred.
• In one embodiment,channels26 may be made by dipping a core or substrate such as a wire of a suitable diameter in a solution of gelatin. The gelatin solution is typically prepared by dissolving a gelatin powder in de-ionized water or sterile water for injection and placing the dissolved gelatin in a water bath at a temperature of approximately 55° C. with thorough mixing to ensure complete dissolution of the gelatin. In one embodiment, the ratio of solid gelatin to water is approximately 10% to 50% gelatin by weight to 50% to 90% by weight of water. In an embodiment, the gelatin solution includes approximately 40% by weight, gelatin dissolved in water. The resulting gelatin solution preferably is devoid of any air bubbles and has a viscosity that is between approximately 200-500 cp and more preferably between approximately 260 and 410 cp (centipoise).
• Once the gelatin solution has been prepared, in accordance with the method described above, supporting structures such as wires having a selected diameter are dipped into the solution to form the gelatin channels. Stainless steel wires coated with a biocompatible, lubricious material such as polytetrafluoroethylene (Teflon) are preferred.
• Typically, the wires are gently lowered into a container of the gelatin solution and then slowly withdrawn. The rate of movement is selected to control the thickness of the coat. In addition, it is preferred that a the tube be removed at a constant rate in order to provide the desired coating. To ensure that the gelatin is spread evenly over the surface of the wire, in one embodiment, the wires may be rotated in a stream of cool air which helps to set the gelatin solution and affix film onto the wire. Dipping and withdrawing the wire supports may be repeated several times to further ensure even coating of the gelatin. Once the wires have been sufficiently coated with gelatin, the resulting gelatin films on the wire may be dried at room temperature for at least 1 hour, and more preferably, approximately 10 to 24 hours. Apparatus for forming gelatin tubes are described below.
• Once dried, the formed microfistula gelatin channels are treated with a cross-linking agent. In one embodiment, the formed microfistula gelatin films may be cross-linked by dipping the wire (with film thereon) into the 25% glutaraldehyde solution, at pH of approximately 7.0-7.8 and more preferably approximately 7.35-7.44 at room temperature for at least 4 hours and preferably between approximately 10 to 36 hours, depending on the degree of cross-linking desired. In one embodiment, formed channel is contacted with a cross-linking agent such as gluteraldehyde for at least approximately 16 hours. Cross-linking can also be accelerated when it is performed a high temperatures. It is believed that the degree of cross-linking is proportional to the bioabsorption time of the channel once implanted. In general, the more cross-linking, the longer the survival of the channel in the body.
• The residual glutaraldehyde or other cross-linking agent is removed from the formed channels by soaking the tubes in a volume of sterile water for injection. The water may optionally be replaced at regular intervals, circulated or re-circulated to accelerate diffusion of the unbound glutaraldehyde from the tube. The tubes are washed for a period of a few hours to a period of a few months with the ideal time being 3-14 days. The now cross-linked gelatin tubes may then be dried (cured) at ambient temperature for a selected period of time. It has been observed that a drying period of approximately 48-96 hours and more typically 3 days (i.e., 72 hours) may be preferred for the formation of the cross-linked gelatin tubes.
• Where a cross-linking agent is used, it may be desirable to include a quenching agent in the method of makingchannel26. Quenching agents remove unbound molecules of the cross-linking agent from the formedchannel26. In certain cases, removing the cross-linking agent may reduce the potential toxicity to a patient if too much of the cross-linking agent is released fromchannel26. Formedchannel26 is preferably contacted with the quenching agent after the cross-linking treatment and, preferably, may be included with the washing/rinsing solution. Examples of quenching agents include glycine or sodium borohydride.
• The formed gelatin tubes may be further treated with biologics, pharmaceuticals or other chemicals selected to regulate the body's response to the implantation ofchannel26 and the subsequent healing process. Examples of suitable agents include anti-mitolic pharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen, Avastin, VEGF or steroids).
• After the requisite drying period, the formed and cross-linked gelatin tubes are removed from the underlying supports or wires. In one embodiment, wire tubes may be cut at two ends and the formed gelatin tube slowly removed from the wire support. In another embodiment, wires with gelatin film thereon, may be pushed off using a plunger or tube to remove the formed gelatin channel.
• FIGS. 16 and 17 show two alternative methods and apparatus for forming gelatin channels. InFIG. 16,apparatus140 includes a suspendedwire142 that may be introduced into avacuum chamber144 at a temperature of 20° C. Thegelatin solution146 maintained at 55° C. may be applied to the wire invacuum chamber144 by spraying viaair jet148.Wire142 is rotated by rotatingapparatus150 to ensure that the sprayed gelatin is applied evenly to the surface ofwire142.
• InFIG. 17, a further alternative embodiment of forming gelatin tubes is shown. In accordance with the embodiment ofFIG. 17, awire142 attached to arotating apparatus150 is dipped into thegelatin solution163 at 55° C. as generally described above.Wire142 is dipped into and removed, from the gelatin solution repeatedly and sprayed with air to ensure an even coat of the gelatin film onto the wire. In either embodiment ofFIGS. 16 and 17, the gelatin tubes formed thereby may be further subjected to a cross-linking step desired above.
• The gelatin tube may also be formed by preparing the mixture as described above and extruding the gelatin into a tubular shape using standard plastics processing techniques. Preparingchannel26 by extrusion allows for providing channels of different cross sections. For example, as shown inFIG. 34,channels26 having two or more passageways260 may be provided, allowing for flow regulation. In one embodiment, passageways260 may be selectively opened or obstructed, as shown in the shading onFIG. 34(d) to selectively control flow therethrough. One of the passageways260 may be adapted to receiveguidewire28 or, in the alternative,channel26 ofFIG. 34 may be used (and implanted) without a guidewire, as previously described.Channel26 shown inFIG. 34 may also provide greater structural integrity after implantation.
• FIG. 18 shows anautomated apparatus160 for preparing a plurality of microfistula gelatin tubes. Shown inFIG. 18 is anapparatus160 that includes a temperature controlledbath162 of thegelatin solution163. The apparatus includes aframe164 that carries a verticallymovable dipping arm166. The dipping arm is coupled to agear box168 which is actuated by a rotary motor. The dipping arm includes a plurality of clamps (not shown) for holdingseveral mandrel wires170 for dipping into the gelatin solution. As further shown inFIG. 18,mandrel wires170 may further includeweights172 suspended at their distal ends to ensure that the wire remains substantially straight (without kinking or curving) and to dampen oscillations or vibrations when being dipped in thegelatin solution163. The operation ofapparatus160 may be controlled by a controller such as a computer with commands for dipping and withdrawal of the wires from the gelatin solution. Astirrer176 may be provided to ensure the consistency of the gelatin solution. After the gelatin tubes have been formed, the tubes are dried and cross-linked as described above.
• Channels26 made in accordance with the methods described above, allow for continuous and controlled drainage of aqueous humor from the anterior chamber of the eye. The preferred drainage flow rate is approximately 2 microliters per minute, although by varying the inner diameter and length ofchannel26, the flow rate may be adjusted as needed. One ormore channels26 may be implanted into the eye of the patient to further control the drainage.
• In addition to providing a safe and efficient way to relieve intraocular pressure in the eye, it has been observed that implanted channels disclosed herein can also contribute to regulating the flow rate (due to resistance of the lymphatic outflow tract) and stimulate growth of functional drainage structures between the eye and the lymphatic and/or venous systems. These drainage structures evacuate fluid from the subconjunctiva which also result in a low diffuse bleb, a small bleb reservoir or no bleb whatsoever.
• The formation of drainage pathways formed by and to the lymphatic system and/or veins may have applications beyond the treatment of glaucoma. Thus, the methods of channel implantation may be useful in the treatment of other tissues and organs where drainage may be desired or required.
• In addition, it has been observed that as the microfistula channel absorbs, a “natural” microfistula channel or pathway lined with cells is formed. This “natural” channel is stable. The implanted channel stays in place (thereby keeping the opposing sides of the formed channel separated) long enough to allow for a confluent covering of cells to form. Once these cells form, they are stable, thus eliminating the need for a foreign body to be placed in the formed space.
• While the methods, apparatus and systems of this disclosure have been described with reference to certain embodiments, it will be apparent to those skilled in the art that numerous modifications and variations can be made within the scope and spirit of the inventions as recited in the appended claims.

Claims (35)

1. A method, of implanting a channel into a patient's eye, comprising:

advancing a distal portion of a delivery device through the cornea or the limbus of the eye and transocularly across the anterior chamber of the eye;

advancing the distal portion of the delivery device through eye tissue from the anterior chamber to a subconjunctival space of the eye without penetrating the conjunctiva of the eye;

advancing the channel, within the distal portion of the delivery device, relative to the delivery device, such that a distal end of the channel becomes distal to the distal end of the delivery device and becomes positioned within the subconjunctival space of the eye; and

withdrawing the delivery device, relative to the channel, such that the distal end of the channel remains positioned in the subconjunctival space and the delivery device is removed from the eye.

2. The method ofclaim 1, wherein the channel is positioned such that the distal end of the channel is positioned in the subconjunctival space and a proximal end is positioned in the anterior chamber of the eye.

3. The method ofclaim 1, wherein the eye tissue, through which the channel is advanced, comprises trabecular meshwork.

4. The methodclaim 1, wherein advancing through eye tissue comprises advancing the distal portion of the delivery device over a guidewire that extends through the eye tissue to the subconjunctival space.

5. The methodclaim 4, wherein the guidewire extends through a lumen of the channel during the advancing through eye tissue.

6. The methodclaim 4, further comprising withdrawing the guidewire proximally through a lumen of the channel after the advancing the channel.

7. The methodclaim 1, wherein advancing the channel comprises advancing a pusher distally within the delivery device, such that a distal end of the pusher abuts a proximal end of the channel, and distal advancement of the pusher relative to the delivery device advances the channel distally relative to the delivery device.

8. The methodclaim 7, further comprising withdrawing the pusher proximally relative to the delivery device after the advancing the channel.

9. The methodclaim 7, further comprising advancing a guidewire, extending through the delivery device and channel, through eye tissue prior to the advancing the channel.

10. The method ofclaim 9, further comprising partially retracting the delivery device until the distal end of the pusher is visible

11. The method ofclaim 10, further comprising withdrawing the guidewire after the delivery device is partially retracted and the distal end of the pusher is visible.

12. The method ofclaim 1, wherein the delivery device comprises an arcuate distal portion and the channel resides in the arcuate distal portion prior to implanting the channel in the eye.

13. The method ofclaim 1, wherein advancing the channel comprises advancing the channel at a rate of from 0.25-0.65 mm/sec.

14. The method ofclaim 1, wherein the channel, after implantation, provides a flow pathway with a diameter of from approximately 50 microns to approximately 250 microns.

15. A method, of implanting a channel into a patient's eye, comprising:

advancing a distal portion of a delivery device through an anterior portion of the eye and transocularly across the anterior chamber of the eye;

advancing the distal portion of the delivery device through eye tissue, such that a passageway is created by the delivery device from the anterior chamber of the eye, through the eye tissue, and to a natural space of the eye;

advancing the channel, within the distal portion of the delivery device, relative to the delivery device, such that a distal end of the channel is advanced distal to the distal end of the delivery device and becomes positioned within the natural space of the eye; and

withdrawing the delivery device, relative to the channel, such that the channel remains extending from the anterior chamber of the eye to the natural space of the eye, and such that the delivery device is removed from the eye.

16. The method ofclaim 15, wherein the anterior portion of the eye, through which the distal portion of the delivery device is advanced, comprises a cornea or a limbus of the eye.

17. The method ofclaim 15, wherein the eye tissue, through which the channel is advanced, comprises trabecular meshwork.

18. The method ofclaim 15, wherein the natural space of the eye comprises a subconjunctival space of the eye.

19. The method ofclaim 18, wherein the advancing through eye tissue does not penetrate the conjunctiva.

20. The method ofclaim 18, wherein the channel extends, after implantation, from the anterior chamber, through trabecular meshwork, and to the subconjunctival space.

21. The method ofclaim 15, wherein the natural space of the eye comprises a suprachoroidal space of the eye.

22. The method ofclaim 21, wherein the channel extends, after implantation, from the anterior chamber, through trabecular meshwork, and to the suprachoroidal space.

23. The methodclaim 15, wherein advancing through eye tissue comprises advancing the distal portion of the delivery device over a guidewire that extends through the eye tissue.

24. The methodclaim 23, wherein the guidewire extends through a lumen of the channel during the advancing through eye tissue.

25. The methodclaim 15, wherein advancing the channel comprises advancing a pusher distally within the delivery device, such that a distal end of the pusher abuts a proximal end of the channel, and distal advancement of the pusher relative to the delivery device advances the channel distally relative to the delivery device.

26. The method ofclaim 25, further comprising partially retracting the delivery device until the distal end of the pusher is visible beyond the distal end of the delivery device.

27. The method ofclaim 15, wherein advancing the channel comprising advancing the channel at a rate of from 0.25-0.65 mm/sec.

28. The method ofclaim 15, wherein the channel, after implantation, provides resistance to flow, such that intraocular pressure is maintained between approximately 10-18 mmHg.

29. The method ofclaim 15, wherein the channel, after implantation, provides a flow pathway with a diameter of from approximately 50 microns to approximately 250 microns.

30. A method, of implanting a channel into a patient's organ, comprising:

advancing a distal portion of a delivery device through a first surface of organ tissue to a space of the organ, such that a passageway is created by the delivery device through the first surface to the space of the organ;

advancing the channel, with a pusher disposed within the distal portion of the delivery device, relative to the delivery device, such that a distal end of the channel is advanced distal to the distal end of the delivery device and is positioned within the space of the organ;

withdrawing the delivery device, relative to the channel and the pusher, until a proximal end of the channel is distal to the distal end of the delivery device; and

withdrawing the delivery device and the pusher from the organ, such that the channel remains extending from the first surface of the organ tissue, through the organ tissue, to the space of the organ.

31. The methodclaim 30, wherein advancing the distal portion comprises advancing the distal portion of the delivery device over a guidewire that extends through the organ tissue.

32. The methodclaim 31, wherein the guidewire extends through a lumen of the channel during the advancing the distal portion.

33. The methodclaim 30, wherein advancing the channel comprises advancing the pusher distally within the delivery device, such that a distal end of the pusher abuts the proximal end of the channel, and distal advancement of the pusher relative to the delivery device advances the channel distally relative to the delivery device.

34. The method ofclaim 33, further comprising partially retracting the delivery device until the distal end of the pusher is visible beyond the distal end of the delivery device.

35. The method ofclaim 30, wherein advancing the channel comprising advancing the channel at a rate of from 0.25-0.65 mm/sec.

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