Abstract:
Devices, methods, tools, and kits for surgically separating two pressure-sensitive vessels (e.g., arteriole, vein, and/or nerve) at a point of contact or within about 1 mm of the contact. The device includes a biocompatible sheet of material, such as a bridge or separator or external stent. The device is positioned between one or more pressure-sensitive vessels or nerves to alleviate compression with a the tool includes a deployment mechanism and a user interface (e.g., a controller or robot) for inserting the device between the two pressure-sensitive vessels or nerves.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a non-provisional application of and claims priority to U.S. Provisional Patent Application No. 61/551,102, filed on Oct. 25, 2011, the entire contents of which are incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    Hemorrhaging and vision loss can occur from a branch retinal vein occlusion (BRVO) where an arteriole passes over a vein to restrict the passage of blood flow. Retinal vascular disease is a leading cause of blindness. BRVO is the second most common retinal vascular disorder following diabetic retinopathy. Population-based studies reflect an overall adult prevalence of 4.42 per 1000 people or 13.9 million people worldwide with BRVO (R. L. McIntosh et al., “Interventions for branch retinal vein occlusion: an evidence-based systematic review.,”  Ophthalmology,  vol. 114, pp. 835-854, 2007) and occurrence increases with age. BRVO can cause a decrease in vision due to ischemia or edema of the macula, and/or vitreous hemorrhage. More than half of patients with BRVO develop visual acuity worse than 20/40. BRVO typically occurs at arteriovenous crossing sites with the artery positioned anterior to the vein producing compression (G. T. Frangieh et al., “Histopathologic study of nine branch retinal vein occlusions.,”  Arch Ophthalmol.,  vol. 100, pp. 1132-1140, 1982). The Branch Vein Occlusion Study (Anonymous, “Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group,”  Am J Ophthalmol,  vol. 98, pp. 271-82, 1984) and the Standard Care versus Corticosteroid for Retinal Vein Occlusion Study (I. M. Scott IU et al.; SCORE Study Research Group., “A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6.,”  Arch Ophthalmol,  vol. 127, pp. 1115-28, 2009) demonstrated that grid laser is helpful for resolving macular edema. Alternatives have been sought because retinal hemorrhages interfere with laser treatment and laser scars can decrease vision. Medical therapies include intravitreal injection of corticosteroids or VEGF inhibitors to treat the retinal edema rather than the underlying blood flow obstruction. However, a significant number of patients are unresponsive to medical therapy and retain macular edema and poor vision. 
         [0003]    The first report of surgical decompression as a successful potential treatment for BRVO with a vitrectomy and technically challenging separation of the common adventitial sheath of the crossing artery and vein (sheathotomy) was published in 1988 by Osterloh and Charles. C. S. Osterloh M D, “Surgical decompression of branch retinal vein occlusions,”  Arch Ophthalmol.,  vol. 106, pp. 1469-71, 1988. Multiple reports have suggested that vitrectomy with sheathotomy may improve vision in patients with recalcitrant macular edema unresponsive to laser therapy and/or medical therapy. J. Mason et al., “Sheathotomy to decompress branch retinal vein occlusion: a matched control study,”  Ophthalmology,  vol. 111, pp. 540-545, 2004; U. Mester and P. Dillinger, “Vitrectomy with arteriovenous decompression and internal limiting membrane dissection in branch retinal vein occlusion,”  Retina,  vol. 22, pp. 740-746, 2002; I. K. Oh et al., “ Long-term visual outcome of arteriovenous adventitial sheathotomy on branch retinal vein occlusion induced macular edema,”  Korean J Ophthalmol,  vol. 22, pp. 1-5, 2008; B. R. Opremcak E M, “Surgical decompression of branch retinal vein occlusion via arteriovenous crossing sheathotomy: a prospective review of 15 cases,”  Retina,  vol. 19, pp. 1-5, 1999; N. Rodanant and S. Tjoongsuwan, “Sheathotomy without separation of venule overlying arteriole at occlusion site in uncommon branch retinal vein occlusion,”  J Med Assoc Thai.,  vol. 88, pp. 143-150, 2005; S. Yamamoto et al., “Vitrectomy with or without arteriovenous adventitial sheathotomy for macular edema associated with branch retinal vein occlusion,”  Am J Ophthalmol,  vol. 138, pp. 907-914, 2004; J. C. Hwang et al., “ Combined arteriovenous sheathotomy and intraoperative intravitreal triamcinolone acetonide for branch retinal vein occlusion,”  Br J Ophthalmol,  vol. 94, pp. 1483-1489, 2010; G. Shah, “Adventitial sheathotomy for treatment of macular edema associated with branch retinal vein occlusion.,”  Curr Opin Ophthalmol,  vol. 11, pp. 171-4, 2000. 
         [0004]    One study reported no difference between sheathotomy versus intravitreal triamcinolone acetonide injection, but they did not limit their subjects to medically recalcitrant edema (E. J. Chung et al., “ Arteriovenous crossing sheathotomy versus intravitreal triamcinolone acetonide injection for treatment of macular edema associated with branch retinal vein occlusion,38  Graefes Arch Clin Exp Ophthalmol,  vol. 246, pp. 967-974, 2008). Because a one-year course of anti-VEGF ranibizumab may exceed $23,000, (W. E. Smiddy, “ Economic Considerations of Macular Edema Therapies,”  Ophthalmology,  2011) the cost of a highly successful surgical intervention could be cost-effective in BRVO treatment. Precise robotic control would likely reduce iatrogenic surgical complications of vitreous hemorrhage (B. R. Opremcak E M, “Surgical decompression of branch retinal vein occlusion via arteriovenous crossing sheathotomy: a prospective review of 15 cases,” Retina, vol. 19, pp. 1-5, 1999) or localized retinal detachment (M. T. Cahil et al., “The effect of arteriovenous sheathotomy on cystoid macular oedema secondary to branch retinal vein occlusion,”  Br J Ophthalmol,  vol. 87, pp. 1329-1332, 2003) at the arteriovenous sheathotomy site. 
       SUMMARY OF THE INVENTION 
       [0005]    The invention relates to devices, methods, tools, and kits for surgically separating two pressure-sensitive vessels (e.g., an arteriole and a vein) or two nerves or a pressure-sensitive vessel and a nerve at a point of contact or within about 1 mm of the contact. In particular, the invention is directed to minimally invasive micro-surgery of the eye targeting micro blood vessels with characteristic dimensions ranging from about 10-400 μm in diameter. 
         [0006]    The invention also relates to a device comprising a biocompatible sheet of material, such as a bridge or separator or external stent, that is configured for placement between the pressure-sensitive vessels or nerves to permit adequate flow through the vessels and to alleviate any compression. The device is precisely positioned between the pressure-sensitive vessels or nerves with the use of an instrument or tool. 
         [0007]    The tool includes a user interface end (e.g., proximal end) and a working end (e.g., distal end). The device is releasably coupled to the working end, which is inserted into an anatomical target (e.g., eye) to position the device. The user interface can include a microsurgical robotic system that is manipulated by the user for positioning the working end and the device. 
         [0008]    A kit can include one or more instruments and one or more devices (e.g., biocompatible separators or bridges or external stents) and/or a bridge inserter to place between the vessels or nerves, to surgically separate the vessels or nerves. The placement procedure can be enhanced with optical coherence tomography (OCT) visualization and robotic micromanipulation to place the device. 
         [0009]    In one embodiment, the present invention provides a medical device comprising a biocompatible sheet of material configured for insertion between a first pressure sensitive vessel and a second pressure sensitive vessel. 
         [0010]    In another embodiment, the present invention provides a medical device comprising a biocompatible sheet of material configured for insertion between a pressure sensitive vessel and a nerve. 
         [0011]    In yet another embodiment, the present invention provides a medical device comprising a biocompatible sheet of material configured for insertion between a first nerve and a second nerve. 
         [0012]    The invention also provides a method for separating two components in a patient. The method comprises inserting a device through a lumen in the patient, separating a first pressure sensitive vessel from a second pressure sensitive vessel with the device to create an opening, and inserting a biocompatible sheet of material into the opening to maintain separation of at least a portion of the first pressure sensitive vessel and the second pressure sensitive vessel. 
         [0013]    The invention also provides a method for separating two components in a patient. The method comprises inserting a device through a lumen in the patient; separating a first pressure sensitive vessel from a nerve with the device to create an opening, and inserting a biocompatible sheet of material into the opening. 
         [0014]    The invention also provides a method for separating two components in a patient. The method comprises inserting a device through a lumen in the patient, separating a first nerve from a second nerve with the device to create an opening, and inserting a biocompatible sheet of material into the opening. 
         [0015]    The invention also provides a tool for positioning a device to separate two components. The tool comprises a first tube in communication with a user interface, a second flexible tube coupled to and in a telescoping relationship with the first tube, and a third tube coupled to and in a telescoping relationship with the second flexible tube, the device coupled to an outer surface of the third tube, and wherein the device is positioned at least partially between the two components when the third tube is retracted into the second flexible tube. 
         [0016]    The invention also provides a tool for positioning a device to separate two components according to another embodiment. The tool comprises a first tube in communication with a user interface, a second flexible tube coupled to and in a telescoping relationship with the first tube, and a wire coupled to and in telescoping relationship with the second flexible tube, the wire including a deployment section at a distal end thereof, the device coupled to an outer surface of the wire, and wherein the device is configured to slide over the deployment section and onto at least one of the components when the second flexible tube pushes the device over the expansion segment. 
     
    
     DETAILED DESCRIPTION 
       [0017]    Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. 
         [0018]    Although directional references, such as upper, lower, downward, upward, rearward, bottom, front, rear, etc., may be made herein in describing the drawings, these references are made relative to the drawings (as normally viewed) for convenience. These directions are not intended to be taken literally or limit the present invention in any form. In addition, terms such as “first,” “second,” and “third” are used herein for purposes of description and are not intended to indicate or imply relative importance or significance. 
         [0019]      FIG. 1  schematically illustrates a device  10  for separating two pressure sensitive vessels or two nerves or a pressure-sensitive vessel and a nerve according to one embodiment of the present invention. The device  10  includes a sheet of material  14  configured to be positioned between a first pressure sensitive vessel, such as a vein or arteriole, and a second pressure sensitive vessel, such as a vein or arteriole or between two nerves or between a pressure-sensitive vessel and a nerve. As illustrated in  FIG. 1 , the device  10  is positioned between a vein  18  and an arteriole  22  at a crossing  30  (e.g., a location where the vein and arteriole overlap or touch one another). The sheet of material  14  can be flexible or pre-formed. The sheet of material  14  can include a plurality of individual segments that are fused or coupled together that allow the sheet to be flexible and thus able to be manipulated into different configurations depending on the location of use. In some alternative embodiments, the sheet of material  14  is in the form of a half-cylinder. The sheet of material  14  can comprise any suitable material or combinations of materials that are biocompatible with human tissue, such as the retina, including but not limited to one of a super-elastic alloy, a shape memory alloy, and a smart material. In some alternative embodiments, the sheet of material  14  can include nickel titanium (NiTi), ionic polymer metal composite (IPMC) or poly(methyl methacrylate) (PMMA). Additionally, the sheet of material  14  can include drugs or medications embedded therein that elute from the material(s) over time. 
         [0020]    The devices, tools, methods and kits of this invention can be used for similar procedures in other systems in the body for the separation of vessels and/or nerves causing compression or compromised flow. For example, this could include vascular decompression of the trigeminal nerve in trigeminal neuralgia. 
         [0021]    In one example, a retinal venule  26  and arterial  22  crossing  30  was separated in a cadaver pig eye (see  FIG. 2 ). A prototype half-cylinder sheet of material  34  was inserted under the arteriole  38  and over the retinal venule  26 . The position of the half-cylinder sheet of material  34  was imaged by OCT (see  FIG. 2 ).  FIG. 2  shows the half-cylinder sheet of material  34  which is positioned over a cross-section profile of a retinal venule  26  and under a retinal artery  22 . 
         [0022]    The device  10  can be in the form of external stents or bridges and they can be created using the following technologies: 
         [0023]    Super-elastic nickel titanium (NiTi) stents are pre-shaped to wrap over the blood vessel. These stents use a deployment mechanism that supports them in an expanded configuration and provides gradual release around the blood vessel. These stents can also be pre-shaped to a specific diameter based on imaging of the patient&#39;s eye and segmentation of these images to determine the blood vessel size. The pre-shaping process involves wrapping a sheet of NiTi around a wire with a diameter matching the blood vessel then heating the device to about 400-500 degrees Celsius for an hour and then cooling down the device to set its shape. 
         [0024]    Electro-active polymer composites (e.g., ionic polymer metal composite; IPMC) stents can be used in the form of a Nafion strip that curls into shape upon activation. These stents are made of a layer of Nafion between a cathode and an anode layer, upon activation of about 1-2 Volts differential in an aqueous environment the ions are transported to one side of the polymer and cause it to swell and bend. Upon release of voltage these polymers retain their shape. 
         [0025]    A biocompatible polymer such as PMMA pre-formed in a sloping bridge configuration to maintain separation. 
         [0026]    The device  10  is inserted through a lumen in a patient with an apparatus  50 , which includes a deployment mechanism  54  and a user interface such as an external controller  56  (e.g., robot).  FIGS. 3-5  illustrate one embodiment of a deployment mechanism  54  for external devices  10 . The deployment mechanism  54  includes a support tube  58  that is coupled to the controller  56 , a second tube  62 , and a deployment tab  66 . The support tube  58  comprises stainless steel and/or a polymer and is substantially more rigid than the part it holds. The second tube  62  is configured to be received within the support tube  58  and is steerable and bendable. The second tube  62  is independently controlled by the controller  56  and can telescope with respect to the support tube  58  thereby changing length and deployment angle. This second tube  62  can comprise a super elastic NiTi material that is pre-shaped to bend its tip in a circular arc with a predetermined radius. By extending the second tube  62  out of the support tube  58 , the approach angle for deployment of the device  10  is controlled. The deployment tab  66  is configured to be received within the second tube  62  and holds the device  10  in an open and/or extended position. The deployment tab  66  is also independently controlled by the controller  56  and can telescope with respect to the support tube  58  and the second tube  62 . The deployment tab  66  includes a distal end having a tapered tip  70  such that when the deployment tab  66  is retracted into the second tube  62 , the device  10  slides off and the distal end of the device  10  starts curling around to at least partially surround or conform to the outer diameter of the blood vessel to thereby separate the vessel from another vessel or nerve  18 ,  22 . 
         [0027]      FIGS. 6-7  illustrate a second embodiment of a deployment mechanism  60 . This second embodiment utilizes a similar arrangement with the deployment tab  66 , second tube  62 , support tube  58 , and controller  56  as illustrated in  FIGS. 3-5  of the first embodiment of the deployment mechanism  54 . The deployment mechanism  60  includes deployment tab  66  configured to support a plurality of devices  10 . The plurality of devices  10  are arranged on the deployment tab  66  with their longitudinal axis perpendicular to the backbone of the second tube  62 . The deployment tab  66  in this second embodiment includes a release slot  74  in the second tube  62 . The devices  10  are arranged serially in an extended configuration as shown in  FIG. 7 . The deployment tab  66  holds the devices  10  in an extended (open) configuration. When the deployment tab  66  is retracted, the distal end of each of the devices  10  curls gradually around the blood vessel thereby separating the vessel from another vessel or nerve  18 ,  22 . 
         [0028]    One difference between the second embodiment of the deployment mechanism  60  and the first embodiment of the deployment mechanism  54  is that the second embodiment allows for approaching the target blood vessel where the plane containing the second tube  62  is generally perpendicular to the target blood vessel. In the first embodiment of the deployment mechanism, this plane contains the blood vessel. The second embodiment of the deployment mechanism also allows for continuous release of multiple devices  10  while the first embodiment allows for deployment of a pre-loaded device  10  (e.g., a single use tip). 
         [0029]      FIGS. 8-9  illustrate a third embodiment of a deployment mechanism  76  coupled to a controller  80  (e.g., robot). The deployment mechanism  76  in this embodiment includes a pre-bent support tube  78  that allows for adjustment of its distal tip location inside the eye or other target area. The deployment mechanism  76  also includes a second tube  82  and a deployment tab  86 . The second tube  82  is configured to be received within the support tube  78  and is steerable and bendable. The second tube  82  is independently controlled by the controller  80  and can telescope with respect to the support tube  78  thereby changing length and deployment angle. 
         [0030]    The deployment tab  86  is generally configured as a conduit or wire with a deployment section  90  at its distal end. The deployment tab  86  is configured to be at least partially received within the second tube  82 . The deployment tab  86  is independently controlled by the controller  80  and can telescope with respect to the support tube  78  and the second tube  82 . The deployment section  90  includes a first segment  94  (e.g., expansion segment) where a width (or diameter) of the first segment gradually increases from a proximal end to a mid-section and a second segment  98  (e.g., gradual release segment) where a width (or diameter) of the second segment gradually decreases from the mid-section to a distal end. The deployment section  90  serves a dual-purpose of expanding the device  10  and gradually releasing it to surround or conform to the blood vessel. The release of the device  10  is controlled by a gradual pushing of the second tube  82  in order to gradually advance the device  10  along the axis of the deployment tab  86 . The deployment section  90  includes a recessed area  102  configured to receive a blood vessel such that the axis of the deployment tab  86  is substantially coaxial with the axis of at least a portion of the blood vessel. As the device  10  is advanced along the deployment tab  86  and the deployment section  90 , the device  10  gradually expands as it traverses along the first segment  94  of the deployment section  90 . As the device  10  continues along the deployment section  90 , the device  10  is positioned on the blood vessel (or nerve) as it gradually slides off of the second segment  98  of the deployment section  90 . The device  10  then gradually contours or at least partially surrounds an external surface of the target blood vessel thereby separating the vessel from another vessel or nerve  18 ,  22 . The second tube  82  can include longitudinal slots that allow a distal end to elastically expand as it pushes the device  10  over or along the deployment section  90 . 
         [0031]    Various features of the invention are set forth in the following claims.