Neuro guidewire devices and related systems and methods for treatment of ophthalmic diseases

Abstract

A neuro guidewire device (1300) for treatment of obstructions within vasculature behind a subjects eye includes a corewire (1305) having a first section (1310) at a distal end of the corewire (1305), a second section (1320), and a third section (1325) having a first tapered portion (1345) at a distal end, a first corewire section proximal to the first tapered portion (1345), and having a constant diameter, a second tapered portion (1350) proximal to the first corewire section, a second corewire section proximal to the second tapered portion, and having constant diameter, a third tapered portion (1355) proximal to the second corewire section, and a fourth section (1330), proximal to the third section (1325), the fourth section (1330) having a constant diameter. The neuro guidewire (1300) device further includes a coil (1335) provided around the first (1310), the second (1320), and at least a portion of the third section (1325).

Description

Attorney Docket No. 00170-0032-00304NEURO GUIDEWIRE DEVICES AND RELATED SYSTEMS AND METHODS FOR TREATMENT OF OPHTHALMIC DISEASESCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 694,236, filed on September 13, 2024, the entirety of which is incorporated herein by reference.FIELD OF THE INVENTION

[0002] The present disclosure relates to intravascular guidewire devices and to methods of using the same. More specifically, the present disclosure relates to a neuro guidewire (nGW) device (or an ophthalmic artery guidewire device) for use as part of a system for treatment of obstructions (e.g., stenosis, lesions, and plaques) within neurovascular anatomy for the purpose of treating ophthalmic diseases..BACKGROUND

[0003] Guidewires (GWs) are routinely used to diagnose and treat diseases in the peripheral, coronary, and neurovascular anatomy. Use of GWs is an integral part of intravascular diagnostic and therapeutic procedures today. GWs are typically formed of a solid corewire with a flexible distal coil or spring of 20 cm or more in length, often made from a radiopaque material. The corewire is tapered from the distal end proximally from a smaller diameter to a larger diameter. Corewire tapering serves to increase flexibility of the GW and to provide atraumatic capability while the GW is within the vasculature, e.g., within a vessel. A coil spring is typically affixed to a distal end of the corewire by welding or soldering and extends proximally to a point at which an inside diameter of the coil spring matches an outside diameter of the corewire. Platinum is usually selected as the material used to form the coil spring, in certain segments, as it provides radiopacity for visualization under fluoroscopy. This visualization aids a user during navigation of the GW within the vasculature. Navigating or steering the GW is accomplished by rotationally manipulating a proximal-most section of the GW while advancing the GW under fluoroscopy. The first steerable neuro GW (nGW) devices were designed for specific use in the neurovascular anatomy, e.g., in neuro circulation. These nGW devices were designed for intracranial navigation in conjunction with a microcatheter for use in conventional neurovascular anatomy. The use of nGW devices in the neurovascular anatomy allowed for the development and use of devices to treat aneurysms,Attomev Docket No. 00170-0032-00304 clots, and other neurological issues. nGW devices continue to be an integral part of neuro interventional procedures today.

[0004] However, nGW devices have not specifically been designed for use within the vasculature behind an eye of a subject. The present disclosure is directed to intravascular GWs and related systems and methods of using the same, for treatment of obstructions (e.g., stenosis, lesions, plaques) within the vasculature behind an eye of a subject for treatment of eye diseases (that is. ophthalmic diseases).SUMMARY

[0005] In one aspect, the present disclosure is directed to a neuro guidewire device for treatment of obstructions within vasculature behind an eye of a subject, the neuro guidewire device comprising: a corewire having a plurality of sections, including: a first section at a distal end of the corewire, the first section being tapered and having a minimum diameter at the distal end of the corewire, and a maximum diameter at a proximal end of the first section; a second section, proximal to the first section, the second section being tapered and having a minimum diameter at a distal end of the second section, and a maximum diameter at a proximal end of the second section; a third section, proximal to the second section, the third section having: a first tapered portion at a distal end of the third section, the first tapered portion having an increasing diameter from a distal end of the first tapered portion to a proximal end of the first tapered portion; a first corewire section proximal to the first tapered portion, and having a constant diameter; a second tapered portion proximal to the first corewire section and decreasing in diameter from a distal end of the second tapered portion to a proximal end of the second tapered portion; a second corewire section proximal to the second tapered portion, and having a constant diameter; and a third tapered portion proximal to the second corewire section and increasing in diameter from a distal end of the third tapered portion to a proximal end of the third tapered portion; and a fourth section, proximal to the third section, the fourth section having a constant diameter; and a coil provided around at least the first section, the second section, and at least a portion of the third section.

[0006] In another aspect, the present disclosure is directed to a neuro guidewire device for treatment of obstructions within vasculature behind an eye of a subject, the neuro guidewire device comprising: a corewire having a plurality of sections, including: a first section at a distal end of the corewire, the first section being tapered and having a minimum diameter at a distal end of the corewire, and a maximum diameter at a proximal end of the first section; a second section, proximal to the first section, the second section having: a first taperedAttomev Docket No. 00170-0032-00304 portion, extending from the proximal end of the first section, and increasing in diameter from a distal end of the first tapered portion to a proximal end of the first tapered portion; and a second tapered portion, proximal to the first tapered portion, and increasing in diameter from a distal end of the second tapered portion to a proximal end of the second tapered portion; and a third section, proximal to the second section, the third section having a constant diameter; and a coil provided around at least the first section and at least a portion of the second section.

[0007] In still another aspect, the present disclosure is directed to a method of using a neuro guidewire device, such as one of the neuro guidewire devices described above, for treatment of obstructions within vasculature behind an eye of a subject, the method comprising: placing a catheter sheath introducer into the subject; and placing the neuro guidewire device through the catheter sheath introducer, until a distal end of the neuro guidewire device is positioned at a predetermined location within an ophthalmic artery (OA) of the subject, or distal to the OA.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is a digital image of vasculature behind an eye of a human subject, and in particular, shows an ophthalmic artery' (OA) and an internal carotid artery (ICA).

[0009] FIG. 2A is a digital image depicting the vasculature of a subject without age-related macular degeneration (AMD), and FIG. 2B is a digital image depicting the vasculature of a subject with AMD.

[0010] FIG. 3 A is a digital image showing histopathology' of a normal OA as it branches from the ICA, FIG. 3B is a digital image showing histopathology' of an OA blocked at the ostium of the OA and the ICA, and FIG. 3C is a digital image showing histopathology of medial calcifications in the short limb (SL) of the OA.

[0011] FIG. 4A is a digital image that shows an nGW device prolapsing as it is advanced into the OA, and FIG. 4B is a digital image that shows an nGW device successfully advanced through the OA and navigated down to the central retinal artery (CRA).

[0012] FIG. 5A is a digital image of an OA branching off of an ICA and FIG. 5B is a detail view of a takeoff angle, at the origin of the OA shown in FIG. 5B.

[0013] FIG. 6 is a digital image depicting a length from an origin of an OA to a CRA branch.

[0014] FIG. 7 is a diagram showing an ICA and an OA.

[0015] FIG. 8A, FIG. 8B, and FIG. 8C are digital images depicting three examples of OA takeoff angles.

[0016] FIG. 9 is a map of the Bouthillier classification system.Attorney Docket No. 00170-0032-00304

[0017] FIG. 10 is a flowchart of a method of using an nGW device within vasculature behind an eye of a subject for treatment of a disease.

[0018] FIG. 11 is a schematic of the vasculature of a subject and shows a general anatomical view of target anatomy with an nGW device and a catheter therein.

[0019] FIG. 12 is a schematic of the same anatomical view show n in FIG. 11.

[0020] FIG. 13 is a schematic of an nGW device according to one embodiment of the present disclosure.

[0021] FIG. 14 is a schematic of an nGW device according to another embodiment of the present disclosure.

[0022] FIGs. 15A and 15B are schematics of a distal tip section of an nGW device according to one or more embodiments of the present disclosure.DETAILED DESCRIPTIONAnatomy

[0023] With reference to FIG. I . anatomy of the vasculature behind an eye of a human subject will be described. In particular, FIG. 1 is a digital image showing the internal carotid artery' (ICA) 100, and the ophthalmic artery (OA) 105, including a short limb (SL) 110 of the OA 105, an angle ‘a‘ 115 of the OA 105, a long limb (LL) 120 of the OA 105, an angle ‘b’ 125 of the OA 105, and a distal part 130 of the OA 105. The OA 105 is an autoregulating, terminal branch of the ICA 100. and provides the majority' supply of blood to the eye. FIG. 1 shows the OA 105 as a branch of the ICA 100, and depicts the arrangement of the OA 105, including the arrangement of the SL 110, the angle ‘a’ 115, the LL 120, the angle ‘b’ 125, and the distal part 130 of the OA 105, as it branches from the ICA 100 in a non-diseased vessel.

[0024] The retina (not shown) is supplied with oxygenated blood by the OA 105, and rests in the back of the eye. It contains approximately 126 million photoreceptors. These photoreceptors are the most metabolically active tissue in the human body, and consume more oxygen than any other tissue in the human body. Any disruption or blockage (i . e. , interruption) of normal blood flow' rates to the eye impacts the flow of nutrients into and the flow of waste products out of the eye. This flow' alteration may cause a lack of oxygen flow (via a lack of blood flow) to the photoreceptors and may allow' for the accumulation of w aste products. These conditions may cause devastating injury to photoreceptors and in turn, may have a negative effect on vision. In some cases, irreversible vision damage may result.Attorney Docket No. 00170-0032-00304

[0025] FIG. 2A is a digital image of the vasculature of a subject without age-related macular degeneration (AMD), including an ICA 200A and an OA 205A, and FIG. 2B is a digital image of the vasculature of a subject with AMD, including an ICA 200B and an OA 205B. Note the OA 205B of the subject with AMD, shown in FIG. 2B, is blocked by stenosis 210.

[0026] FIG. 3A is a digital image depicting histopathology7of a normal OA 305 A as it branches from an ICA 300A. FIG. 3B is a digital image depicting histopathology of an OA 305B that is blocked at the ostium of the OA 305B and an ICA 300B by a lesion 310 (also referred to as a total occlusion OA), and FIG. 3C is a digital image depicting histopathology of an CL 315C of an OA 305C, with medial calcifications 320C. The vasculature of FIGs. 3B and 3C would be treatment targets for the systems and methods of the present disclosure.

[0027] In the example of the OA in a patient with AMD, treatment may be indicated in cases where luminal stenosis is 50% or less, where the luminal percentage stenosis is defined as: % stenosis = 1 —Dstenosisx 100, where Dstenosis is the diameter of a stenosed segment of normal vasculature, such as a cerebral artery, and Dnormai is a diameter of a normal, proximal segment of the vasculature, such as the cerebral artery. This formula is known as the WASID method for measuring stenosis. In one example of use of the nGW device and the related systems and methods of the present disclosure, OA lesions causing luminal stenosis in the range of about 20% to about 40% may be treated. It has not been previously contemplated that treatment of lesions causing luminal stenosis of less than 50% would be meaningful, particularly in what is considered intracranial circulation.

[0028] As previously mentioned, photoreceptors are the most metabolically active tissue in the human body, and, as a result, luminal stenosis of less than 50% may have a devastating effect on the photoreceptors. Table 1 lists examples of OAs, and specifically, OAs of specific diameters, cross-sectional areas thereof, percentage decrease in cross-sectional areas, and percentage stenosis based on the percentage decrease in cross-sectional areas. In particular, in example OA number 2, a 16% stenosis, as measured by the WASID method, has an impact equivalent to a 30% reduction in cross-sectional blood flow area. Further, in example OA number 4, a 50% stenosis has a 75% reduction in cross-sectional blood flow area. At least these two example OAs show that luminal stenosis of 50% or less can have an impact equivalent to a percentage decrease in cross-sectional area of, for example. 30.56%, 55.56%, or 75%, and, therefore, a luminal stenosis of 50% or less can significantly affect blood supply to the photoreceptors. The percentage stenosis column represents a percentage difference in the diameter of a healthy vessel (row 1) as compared to a stenosed vessel (rows 2-7) in a singleAttomev Docket No. 00170-0032-00304 plane only (that is, in two dimensions, or 2D), based on a single diametric measurement from that plane, and does not reflect the effect of stenosis on the total cross-sectional vessel area of a vessel. The percentage decrease in cross-sectional area (CS A) column represents a percentage difference between a healthy vessel (row 1) and stenosed vessels (rows 2-7) based on cross- sectional area, which is a sum of all the diametric measurements of the vessel in three dimensions, that is, in 3D. This comparison of 3D measurements is more representative, as it describes or accounts for all of the cross-sectional reduction of the vessel.TABLE 1

[0029] In addition to not appreciating lower levels (percentages) of stenosis having significant effect on volumetric blood flow through small diameter arteries or vessels, there is also a lack of appreciation for the complexity of the OA anatomy and the degree of difficulty in accessing and treating the OA anatomy using conventional tools. One challenging aspect of this treatment is accessing the desired treatment location within the OA. Current nGW devices are not designed for use in this area (that is, in the vasculature behind the eye), and do not address this unique anatomy, which is smaller in diameter, and which is angulated and significantly more tortuous as compared to typical neuro vessels or cardiovascular vessels, and, because of that tortuosity, current nGW devices do not provide adequate support to establish purchase for a therapeutic device to enter the OA. In addition, current nGW devices do not provide the physician with a method for determining if a specific position within the OA has been reached.

[0030] FIG. 4A is a digital image that shows an nGW device 400A prolapsing as it is advanced into an OA 405A, from an ICA 410A, and FIG. 4B is a digital image that shows anAttomev Docket No. 00170-0032-00304 nGW device 400B successfully advanced through the OA 405B and navigated down past a central retina artery (CRA) (not shown). Placement of the nGW device 400B in the OA 405B down to and past the CRA allows the nGW device 400B to have proper purchase in the OA 405B so that a user (e.g., a physician) can easily manipulate other treatment devices, such as angioplasty balloons and other devices, over the nGW device 400B to provide therapy or treatment. In addition to placement down to and past the CRA, the nGW devices of the present disclosure are configured such that they are easily steered to avoid accessing the CRA. In addition, these nGW devices are optimized to access OA ostiums with retrograde takeoff angles, that is, an angle between an ICA and an OA branching therefrom, in a range of about 45° to about 140°, and to be placed within portions of the OA betw een the ostium down to the CRA.

[0031] FIG. 5 A is a digital image of an OA 505 branching off of an ICA 500, and in particular, depicts a takeoff angle 0, at the origin of the OA 505, which contributes to the difficulty in accessing the OA 505, as the OA 505 branches from or takes off from the ICA 500. As an example, the takeoff angle 0. shown in detail in FIG. 5B, may be about 78°

[0032] The nGW devices described herein are configured for access and placement, as part of a system, within the OA, and to have optimized diametric section dimensions and overall lengths, with relatively improved flexibility, torqueability, pushability to address the unique anatomy of the vasculature behind the eye, including the OA. Optimization of these particular features or properties of the nGW devices contributes directly to the ability of the nGW devices to access, properly locate or position, and aid in the delivery of therapy to the OA. The diameter of the OA as it branches off of the ICA, also referred to as the origin diameter, may be in a range of about 1.2 mm to about 2 mm in a healthy human subject. The origin diameter in a diseased human subject may be much less than the lower end of this range (i.e., much less than about 1.2 mm). In addition, portions of the OA closer to the eye (in other words, more distal portions of the OA) typically have reduced diameters, which may be less than about 1 mm along the segment from the origin of the OA to the branch of the CRA, and beyond. In the example for treatment of the OA, the target area includes the OA origin at the ICA and continues distally (that is, towards the eye) until just proximal to the branch of the CRA (that is, the CRA branch) from the OA. This total length may be in the range of about 10 mm to about 25 mm. FIG. 6 is a digital image depicting the length from the origin O of the OA 605 to the CRA branch 610, which may be approximately 22.4 mm. It may be desirable to treat anywhere along this portion or length of the OA 605 with the nGW device and related systems and methods, as described herein. A portion 605A of the OA 605 shown in FIG. 6 isAttomev Docket No. 00170-0032-00304 one example of a target location for placement of the distal tip of the nGW device of the present disclosure.

[0033] An area of particular interest for treatment with an nGW device according to the present disclosure is the SL of the OA. As noted above, this is the initial branch off of the ICA. FIG. 7 is a diagram showing an ICA 700 and an OA 705. In particular, FIG. 7 shows an origin O of the OA 705 from the ICA 700, and more particularly, shows the ICA 700, a periosteum 710, a point P of penetration of a dural sheath (not shown), the OA 705, an optic nerve 715, an optic canal 720, an SL 725, an angle ‘a’ 735, a long limb 730 of the OA 705, and the portion of the OA 705 that is distal of the LL 730. Typical SL lengths that range from about 0.7 mm to about 2.7 mm.

[0034] As noted above, the OA may branch off of the ICA at an angle (that is, a takeoff angle) in a range of about 45° to about 140° and may contain partial or total occlusions and / or concentric or non-concentric calcified lesions. The takeoff angle and level of occlusion or calcification may contribute to difficulty and access of the OA. The takeoff angle challenge may be further complicated by the position of the OA on the segment of the siphon of the ICA. Different OA positions on the siphon contribute to an increase in access difficulty for an nGW device.

[0035] FIG. 8A, FIG. 8B, and FIG. 8C are digital images depicting three examples of OA takeoff angles ranging from 70° to 132°. Specifically, FIG. 8A depicts an OA 805A with a takeoff angle 0 of 132° from the ICA 800A. FIG. 8B depicts an OA 805B with a takeoff angle 0B of 74° from the ICA 800B. FIG. 8C depicts an OA 805C with a takeoff angle 0c of 70° from the ICA. These images show7OA origins located at different positions on the carotid siphon of the ICA.

[0036] For the purposes of use of the nGW device in the OA. the Bouthillier classification system may be used to identify which ICA segment the nGW device w ould be positioned for treatment. In the case of the OA, the typical OA branch segment location is within the C5 to C6 segments of the ICA, also known as the clinoid or ophthalmic segments. As mentioned, this may vary’ according to anatomy. FIG. 9 is a map of the Bouthillier classification system, and in particular, shows segments of the carotid siphon of the ICA 900, including the target segments for use of an nGW device. FIG. 9 shows the cervical segment (Cl segment), the petrous segment (C2 segment), the lacerum segment (C3 segment), the cavernous segment (C4 segment), the clinoid segment (C5 segment), the ophthalmic segment (C6 segment), and the communicating segment (C7 segment). FIG. 9 also shows the petrolingual ligament P.Attomev Docket No. 00170-0032-00304 nGW Devices and Related Systems and Methods

[0037] The invention of the present disclosure is directed to intravascular GWs and related systems and methods of using the same for treatment of ophthalmic diseases. Specifically, the invention may provide for an nGW device for use as part of a system for treatment of obstructions (e.g., stenosis, lesions, plaques) within anatomy, such as neurovascular anatomy, for the purpose of treating eye disease. One example of use of this nGW device is in a system for use in the ophthalmic artery (OA) for the treatment of eye diseases. It should be noted that fabrication and use of an application specific nGW device for treatment of the OA for eye disease has not been previously contemplated. Existing devices do not address the unique complexities of the OA anatomy for the application of providing endovascular diagnosis and therapy.

[0038] FIG. 10 is a flowchart of a method 1000 of using an nGW device within vasculature behind an eye of a subject for the treatment of a disease, such as AMD, or, put another, for treatment of obstructions within the vasculature behind the eye of the subject. Method 1000 may include a step 1005 of placing a catheter sheath introducer, radially or femorally into a CCA or an ICA of a subject. The catheter sheath introducer can be placed by two different methods:

[0039] 1. Exchange: A diagnostic catheter (DC) may first be used to direct a GW (e.g., a GW having a diameter of about 0.035 in (about 0.889 mm) or about 0.038 in about(0.965 mm)) into the left or right CCA or ICA (that is, a distal end of the GW is positioned within the left or right CCA or ICA). The DC may then be removed, leaving the GW in place. A catheter sheath introducer with a dilator or tracking catheter may then be delivered over the GW to the CCA or the ICA. The GW and dilator or tracking catheter may then be removed, leaving the catheter sheath introducer in place.

[0040] 2. Telescoping: A DC may be preloaded into the catheter sheath introducer, as a system, and the system may be advanced to an aortic arch of the subject, over a GW (e.g., a GW having a diameter of about 0.035 in (about 0.889 mm) or about 0.038 in (about 0.965 mm)). That is, the DC and the catheter sheath introducer may be placed within the subject until a distal end of the DC and a distal end of the catheter sheath introducer are positioned within the aortic arch of the subject. The DC may then be used to direct the GW to the left or right CCA. Other devices, which may be part of the system, may then be tracked over the GW and DC to the CCA or ICA, and then the GW and DC may be removed.

[0041] After placement of the catheter sheath introducer, the method 1000 may include a step 1010 of placing the neuro guidewire device through the catheter sheath introducer until aAttorney Docket No. 00170-0032-00304 distal end of the nGW device is positioned at a predetermined or desired location within the vasculature behind the ey e. The predetermined or desired location may be, for example, within the OA or distal to the OA, and more specifically, the SL of the OA, or locations distal of the SL of the OA, including the superficial temporal artery (STA) or the supraorbital artery (SOA). The step 1010 may include using the following steps (other permutations may be possible):

[0042] 1. Delivering or placing an intermediate catheter (size 6F or smaller, for example) through the catheter sheath introducer and over a GW (e g., a GW having a diameter of about 0.035 in (about 0.889 mm)), which is typically not navigated past the base of the skull or petrous segment (C2) of the ICA, unless specialized wires are used due to the risk of perforation. Then, the GW may be removed, and once the GW has been removed, a smaller GW (e.g., a neuro GW (nGW) device as described herein, and having a diameter of about 0.014 in (about 0.356 mm)) and a microcatheter may be delivered through the intermediate catheter, until a distal end of one or more of the smaller GW and the microcatheter are positioned beyond the petrous segment of the ICA, for OA cannulation.

[0043] 2. In some embodiments, the microcatheter and the smaller GW may be preloaded into the intermediate catheter, as a system (that is, the system may include at least the microcatheter, the smaller GW, and the intermediate catheter, according to some embodiments). The system then be delivered to the ICA through the catheter sheath introducer, and used for OA cannulation.

[0044] As noted above, the smaller GW used in step 1010 may be an nGW device according to one or more embodiments of the present disclosure. The nGW device may be used to enter the OA and may be advanced distally within the OA, until a distal-most tip of the nGW device is distal to the branch of the CRA from the OA. Once the nGW device is in place, the microcatheter may then be removed and a treatment device (e.g., an angioplasty balloon) may be advanced over the nGW device and placed at a target site or location within the vasculature (such as a site within the OA or within the CRA), so that a procedure to treat the disease can be completed. Use of the nGW device may be guided via fluoroscopy. That is, the step 1010 of the method 1000 may include using fluoroscopy to confirm placement of one or more marker bands on the nGW device, such as a marker band on the distal-most tip or distal end of the nGW device, at respective desired or predetermined locations within the OA, such as one of the target sites or locations described herein.

[0045] The nGW device of the present disclosure is configured for use in a specific anatomical application. FIG. 11 is a schematic of the vasculature of a subject, and shows aAttomev Docket No. 00170-0032-00304 general anatomical view of the target anatomy, as well as an nGW device 1100 exiting a catheter 1105 within the ICA 1110, and extending into the OA 1115. The nGW device 1100 may include two marker bands (MB 1 and MB 2), as shown. A single marker band or more than two marker bands may be used. As an example, a marker band may also be placed on a distal-most tip 1100A of the nGW device 1100.

[0046] In the embodiment shown in FIG. 11 , MB 1 marks an exemplary target position of a support segment 1100B of the OA 1 115 for support in the SL 1120 of the OA 1115, and MB 2 marks an exemplary target position an ICA support segment 1100C of the OA 1115, in combination with catheter positioning. A user may verify this positioning under fluoroscopy.

[0047] FIG. 12 is a schematic of the same anatomical view shown in FIG. 11, with several vascular landmarks identified, including an OA origin 1200, a CRA origin 1205. and an area of a superficial temporal artery (STA) 1210, where a distal portion of a GW 1215 may ideally be placed, as shown.

[0048] An overall length of the nGW device of one or more embodiments may range from about 170 cm to about 320 cm. This range encompasses conventional or exchange length nGW configurations. More specifically, the overall length of the nGW device may be in a range of about 300 cm to about 320 cm for an exchange-type nGW device, or in a range of about 180 cm to about 210 cm for a rapid-exchange-type nGW device. The nGW device may include a corewire formed of a material that may be metallic or a polymer, and which may be processed to ensure there is no whipping of the corewire when torqued. Whipping occurs when torque is not effectively transmitted from one end of the corewire to the other end and may result in the corewdre storing torque and, after a period of time, suddenly releasing the torque all at once. The corew ire may be constructed of a single piece of material or multiple segments or strands of material joined together to fabricate a single overall corewire. If constructed of multiple segments of material, each individual segment may possess properties unique to that specific segment, such that there is an overall benefit to the finished nGW device. Material properties taken into consideration for the corewire may include, but are not limited to, cross-sectional shape, tensile strength, surface treatment, and material composition. The corewire may have multiple tapers (that is, a plurality of tapered portions) along its length to facilitate a variety of performance features not commonly found in GWs. In one embodiment, these tapers may begin at a distal end of the nGW device, and extend proximally. In some embodiments, the tapers may extend from the distal end of the nGW device to a proximal end of the nGW device.Attomev Docket No. 00170-0032-00304

[0049] In some embodiments, the corewire may also have a distally placed coiled segment, provided over the distal tapers. In such embodiments, the tapers may provide a variety of diameters that increase from the distal end, proximally along the corewire, to a first point, and then they may decrease in diameter, proximally from the first point, to a second point along the corewire, and then, once again increase in diameter, proximally from the second point. These tapers may be configured to optimize entry and transit of a distal tip of the nGW device into the OA, and in particular, into an SL of the OA and to distal locations of the OA. such as to the STA or to SOA. Reaching these distal OA branches allows for the nGW device to achieve a desired purchase position, such that other devices can be advanced into and withdrawn from the OA without displacing or affecting the position of the nGW device.

[0050] A distal-most section of the corewire may have a tapered segment, which may be slightly stiffer than typical nGW devices, to allow for shaping and to provide for a stable platform to navigate into and through the SL of the OA. A coil may be placed over a distal tip of the corewire, and, when the nGW device is placed within the vasculature of a subject, may extend in a proximal direction to extend to, or nearly to, the OA ostium. The distal-most section of the corewire may be shaped by either the manufacturer or the user. This shape is intended to provide a user with some level of control in avoiding cannulation of the central retinal artery7(CRA), while advancing into the STA or the SOA. The coil may be fabricated of a radiopaque material, typically platinum, to produce a signature visible under fluoroscopy, a non-radiopaque material, such as stainless steel, for selective radiopacity, or a combination thereof. The radiopaque portion of the distal coil may be further be aligned with the specific taper of the nGW device, such that positioning of the nGW device is optimized for delivery7of therapeutic devices into the OA SL, such as balloons. The coil may be fabricated as a single or multi-filar wind to accommodate specific performance characteristics in concert with single or multiple markers located at various lengths to enable measuring or positioning capability. Additionally, the corewire may be modified such that the marker band (or simply, marker(s)) may be provided by use of radiopaque coils, radiopaque polymer sections, selective coil electroplating, coiled wire or polymer marker bands, conventional marker bands, or other methods useful in providing a radiopaque signature. Any of these features may additionally be enabled by fabricating a specific corewire grinding profile to incorporate the particular marker methodology7. The coil of the nGW device may be coated with a polymer to improve mechanical performance or aid in identification of the nGW device. The entirety or a portion of the nGW device may be coated with a material to enhance lubricity. A length of a coated portion of the nGW device may be, for example, betweenAttomev Docket No. 00170-0032-00304 about 30 cm to about 100 cm, or more specifically, about 70 cm. The material for enhancing lubricity may include a hydrophilic coating, polytetrafluoroethylene (PTFE), or other commonly used coatings or combinations to enhance lubricity.

[0051] FIG. 13 shows an nGW device 1300 according to one embodiment. The nGW device 1300 has a corewire 1305 having a plurality of sections, including a first or distal-most section 1310, initiating at a distal end 1315 of the nGW device 1300, and continuing in a proximal direction, a second section 1320 proximal to the first section 1310, a third section 1325 proximal to the second section 1320, and a fourth section 1330, proximal to the third section 1325. The first section 1310 may be tapered, with a narrowest portion or a minimum diameter at the distal end 1315 of the nGW device 1300, and a widest portion or a maximum diameter at a proximal end of the first section 1310. such that a diameter of the first section 1310 increases from the distal end 1315 of the nGW device 1300 to the proximal end of the first section 1310. The first section 1310 may not contain or include a shaping coil. As a result, the first section 1310 of the corewire 1305 may be relatively stiffer as compared to that of corewires of typical nGW devices, so that, when combined with a coil 1335 (e.g., an over- the-corewire coil segment), the nGW device 1300 may provide support for entry and navigation through the OA ostium and on to a distal location of the OA, such as the STA or the SOA. The first section 1310 of the corewire 1305 may extend proximally from the distal end 1315, about 20 mm to about 70 mm, and more specifically, for example, about 20 mm to about 25 mm from the distal end 1315 of the nGW device 1300. As noted above, the nGW device 1300 may include a coil 1335, which may be covered with a hydrophilic coating or a hydrophilic coated polymer jacket. In addition or alternatively, the first section 1310 may have a poly mer covering and the distal end 1315 may be an atraumatic tip. The maximum diameter of the first section 1310 may be less than about 0.014 in (about 0.356 mm), and a diameter of the coil 1335 may be approximately 0.014 in (about 0.356 mm).

[0052] The second section 1320 may also be tapered, and may have a maximum diameter, at a proximal end of the second section 1320, of less than about 0.014 in (about 0.356 mm), and a minimum diameter at a distal end of the second section 1320. The coil 1335 may also extend over the second section 1320, as shown. In addition or alternatively, the second section 1320 may include polymer covering. A length of the second section 1320 may be in a range of about 20 mm to about 70 mm, and, more specifically, in a range of about 20 mm to about 25 mm. The second section 1320 may be tapered, as shown in FIG. 13. or it may have a constant diameter along its length. The second section 1320 is configured to provide support in the SL of the OA so that devices passed over the nGW device 1300 may make theAttomev Docket No. 00170-0032-00304 anatomical turn without dislodging the nGW device 1300. The second section 1320 may include a marker band 1340. which may allow a user to confirm placement of the second section 1320 in the SL of the OA via fluoroscopy. The second section 1320 may also include the coil 1335, as shown. The coil within the second section 1320 may include a radiopaque portion and a non-radi opaque portion, with non-radi opaque portion beginning at about 10 mm or less from a distal end of the second section 1320. In addition, the coil 1335 in this section may be covered with a hydrophilic coating or a hydrophilic coated polymer jacket.

[0053] The third section 1325 may may have an overall length in a range of about 10 mm to about 30 mm, or, more specifically, a length of about 20 mm. In addition, the third section 1325 may have a two corewire sections, namely, a first corewire section 1325a and a second corewire section 1325b having diameters of less than about 0.014 in (about 0.356 mm). The third section 1325 may also have a plurality of transitions or tapered portions, including a first transition or a first tapered portion 1345 at a distal end of the third section 1325, a second transition or a second tapered portion 1350 between the first corewire section 1325a and the second corewire section 1325b, and a third transition or tapered portion 1355 at a proximal end of the third section 1325. The first tapered portion 1345 may begin at a distal end of the third section 1325, and may have an increasing diameter from a distal end of the first tapered portion 1345 to a proximal end of the first tapered portion 1325. The first corewire section 1325a may be proximal to the first tapered portion 1435, and may have a constant diameter. The second tapered portion 1350 may be proximal to the first corewire section 1325a, and may decrease in diameter from a distal end of the second tapered portion 1350 to a proximal end of the second tapered portion 1350. The second corewire section 1325b may be at a proximal end of the second tapered portion 1350, and may have a constant diameter. The third tapered portion 1355 may be proximal to the second corewire section 1325b and may increase in diameter from a distal end of the third tapered portion 1355 to a proximal end of the third tapered portion 1355.

[0054] In some embodiments, a diameter of the second corewire section 1325b may be less than a diameter of the first corewire section 1325a. The diameter of the first corewire section 1325a may be in a range of about 0.010 in (about 0.254 mm) to about 0.014 in (about 0.356 mm), or in a range of about 0.010 in (about 0.254 mm) to about 0.0135 in (about 0.353 mm). In some embodiments, a maximum diameter of the third section 1325 may be about 0.0135 in (about 0.353 mm). In some embodiments, a maximum diameter of the first corewire section 1325 may be about 0.012 in (about 0.305 mm), with a transition or taper between the first corewire section 1325 and the second corewire section 1325b being less than 0.014 in (aboutAttomev Docket No. 00170-0032-003040.356 mm). The coil 1335 may extend at least partially over the first corewire section 1325a. as shown, and the first corewire section 1325a may be covered or coated in a polymer.

[0055] The second corewire section 1325b may have no coil provided thereon, and may also be covered or coated in a polymer. The diameter of the second corewire section 1325b may be less than about 0.014 in (about 0.356 mm), or may in a range of about 0.009 in (about 0.229 mm) to about 0.0125 in (about 0.318 mm). In some embodiments, the diameter of the second corewire section 1325b may be about 0.01 1 in (about 0.279 mm). In one or more embodiments, the third section 1325 may include a marker band, which may extend at least partially over the third tapered portion 1355, to aid in placement within a catheter. In addition, a portion or all of the third section 1325 may have a hydrophilic coating or a hydrophilic coated polymer jacket.

[0056] These relatively smaller diameters of the first corewire section 1325a and the second corewire section 1325b of the third section 1325 may provide the nGW device 1300 with slightly less stiffness when the third section 1325 is between the SL of the OA and a distal opening of a catheter, as compared to known nGW devices. This less stiff segment of the nGW device 1300 may also provide an atraumatic portion while the nGW device 1300 is positioned within in the ICA.

[0057] The fourth section 1330 may extend from the third tapered portion 1355 of the third section 1325, and may have a diameter of about 0.014 in (about 0.356 mm), which may continue to a proximal portion of the nGW device 1300. The fourth section 1330 may have a length so as to make up for the remaining overall length of the nGW device 1300 (that is, a remainder of the overall length of about 300 cm to about 320 cm for an exchange-type GW, or of about 180 cm to about 210 cm for a rapid-exchange-type GW). As with the other sections of the nGW device 1300, a portion or all of the fourth section 1330 may have a hydrophilic coating or a hydrophilic coated polymer jacket. In addition, in some embodiments, one or more additional markers or marker bands may be provided along the fourth section 1330, so that a user can confirm positioning of the nGW device 1300 relative to the vasculature and relative to a microcatheter.

[0058] FIG. 14 shows an nGW device 1400 according to another embodiment. The nGW device 1400 has a corewire 1405 with a plurality of sections, including a first or distal-most section 1410, initiating at a distal end 1415 of the nGW device 1400, and continuing in a proximal direction, a second section 1420, and a third section 1425. The first section 1410 may be tapered, with a narrowest portion near or at the distal end 1415 of the nGW device 1400. and a widest portion near a proximal end of the first section 1410, such that a diameter of the firstAttorney Docket No. 00170-0032-00304 section 1410 increases from the distal end 1415 of the nGW device 1400 to the proximal end of the first section 1410. The first section 1410 may not contain a shaping coil. As a result, the first section 1410 may be relatively stiffer as compared to corewires of known nGW devices so that, when combined with a coil 1430, as shown, the nGW device 1400 may provide support for entry and navigation through the OA ostium and on to a distal location of the OA, such as the STA or the SOA. The first section 1410 may extend proximally from the distal end 1415, or put another way. may have a length in a range of about 20 mm to about 70 mm. In some embodiments, the length of the first section 1410 may be in a range of about 40 mm to about 50 mm. The coil 1430 may be radiopaque and may be covered with a hydrophilic coating or a hydrophilic coated polymer jacket. In addition or alternatively, the first section 1410 may have a polymer covering and the distal end 1415 may be an atraumatic tip. A diameter of the first section 1410 may be less than about 0.014 in (about 0.356 mm). In some embodiments, the diameter of the first section 1410 may be approximately 0.014 in (0.356 mm).

[0059] The second section 1420 may have a maximum diameter of less than about 0.014 in (0.356 mm). The coil 1430 may extend over a portion of the second section 1420, or over all of the second section 1420. In addition or alternatively, the second section 1420 may7include a polymer covering. A length of the second section 1420 may be in a range of about 20 mm to about 70 mm, and, more specifically, in a range of about 40 mm to about 50 mm. The second section 1420 may have a very slight taper (that is, a taper of about 0.0005 in (about 0.0127 mm) to about 0.0020 in (about 0.0508 mm)), as shown, or it may have a constant diameter for its entire length. In some embodiments, the second section 1420 may form a continuous taper with the taper of the first section 1410. The second section 1420 may include a first tapered portion 1435, which forms a continuous taper with the taper of the first section 1410, and a transition or second tapered portion 1440 provided at a proximal end of the second section 1420, as the diameter of the corewire 1405 increases and transitions to the third section 1425. The second section 1420 may provide support when positioned in the SL of the OA, so that one or more additional devices may make the anatomical turn as they pass over the nGW device 1400, without dislodging the nGW device 1400.

[0060] The second section 1420 may include a marker band 1445, which may allow a user to confirm placement of the second section 1420 in a catheter via fluoroscopy. More than one marker band may be provided, in other embodiments, including, for example, a second, proximal marker band (not shown) at a distance of about 150 cm from a distal end of the second section 1420, to allow a user to confirm the second section 1420 is at a tip of aAttomev Docket No. 00170-0032-00304 microcatheter. The second section 1420 may be covered with a hydrophilic coating or a hydrophilic coated polymer jacket. The second section 1420 may also include the coil 1430 extending over at least a portion of the second section 1420. The coil 1430 may change from radiopaque to non-radiopaque along the length of the second section 1420, and in particular, the distal-most length of about 10 mm of the coil 1430 covering the second section 1420 may be radiopaque before changing to non-radiopaque.

[0061] The third section 1425 may extend from the second tapered portion 1440 of the second section 1420, and may have a diameter of about 0.014 in (about 0.356 mm), which may continue to a proximal portion of the nGW device 1400. The third section 1425 may have a length so as to make up for the remaining overall length of the nGW device 1400 (that is, a remainder of the overall length of about 300 cm to about 320 cm for an exchange-type GW, or of about 180 cm to about 210 cm for a rapid-exchange-type GW). As with the other sections of the nGW device 1400, a portion or all of the third section 1425 may have a hydrophilic coating or a hydrophilic coated poly mer jacket. Specifically, a distal-most portion of the third section 1425, such as the distal-most length of about 30 cm to about 50 cm, may have the hydrophilic coating or the hydrophilic coated polymer jacket. In addition, in some embodiments, one or more additional markers or marker bands may be provided along the third section 1425, so that a user can confirm positioning of the nGW device 1400 relative to the vasculature and relative to a microcatheter.

[0062] With reference to FIGs. 15 A and 15B. in one or more additional embodiments, a distal tip section 1505 of an nGW device 1500 (such as the first section 1305 of the nGW device 1300 show n in FIG. 13, or the first section 1410 of the nGW device 1400 shown in FIG. 14) may have a specific shape to optimize the ability of the nGW device 1500 to cannulate the OA. In the embodiment shown in FIGs. 15A and 15B, the distal tip section 1505 of the nGW device 1500 may include a distal-most portion that is 1510 bent or shaped during manufacturing of the nGW device 1 00, or thereafter, so that a final configuration or shape of the distal tip 1505 resembles that of a ‘hockey stick’. The process of shaping is applied to prevent kinking or damage of the nGW device 1500 while providing an additional axis of movement to enable improved cannulation of the OA. The two components of this specific shape are: (1) a length Lisio of a distal-most portion 1510 of the distal tip section 1505, shown in FIG. 15A, and (2) an angle Oisio between the distal-most portion 1510 and the remainder of the distal tip section 1505, shown in FIG. 15B. The length Lisio of the distal- most portion 1510 refers to a length of a distal-most portion of the nGW device 1500, extending from a distalmost tip 1515 in a proximal direction, after shaping, as measured fromAttomev Docket No. 00170-0032-00304 the distal-most tip 1515 to an inner vertex V of the angle Qisio between the distal-most portion 1510 and the remainder of the distal tip section 1505, which is formed after shaping is complete. The angle Oisio refers to an inner angle of bend of the distal -most portion 1510 as measured against the remainder of the distal tip section 1505 of the nGW device 1500. The length L1510 may range from about 1 mm to about 4 mm, and, more specifically, may be about 2.5 mm. The tip angle 61510 may range from about 25° to about 65°, and, more specifically, may be about 45°. This combination of length Lisio and tip angle 61510 may facilitate improved entry of the nGW device 1500 into the OA.

[0063] The embodiments of the nGW devices and the related methods described herein may provide for access and treatment of the OA for eye disease, including angioplasty of the OA. which may improve visual acuity in patients, such as patients with AMD.

[0064] Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims

Attomev Docket No. 00170-0032-00304CLAIMSWe claim:

1. A neuro guidewire device for treatment of obstructions within vasculature behind an eye of a subject, the neuro guidewire device comprising: a corewire having a plurality of sections, including: a first section at a distal end of the corewire, the first section being tapered and having a minimum diameter at the distal end of the corewire, and a maximum diameter at a proximal end of the first section; a second section, proximal to the first section, the second section being tapered and having a minimum diameter at a distal end of the second section, and a maximum diameter at a proximal end of the second section; a third section, proximal to the second section, the third section having: a first tapered portion at a distal end of the third section, the first tapered portion having an increasing diameter from a distal end of the first tapered portion to a proximal end of the first tapered portion; a first corewire section proximal to the first tapered portion, and having a constant diameter; a second tapered portion proximal to the first corewire section and decreasing in diameter from a distal end of the second tapered portion to a proximal end of the second tapered portion; a second corewire section proximal to the second tapered portion, and having a constant diameter; and a third tapered portion proximal to the second corewire section and increasing in diameter from a distal end of the third tapered portion to a proximal end of the third tapered portion; and a fourth section, proximal to the third section, the fourth section having a constant diameter; and a coil provided around at least the first section, the second section, and at least a portion of the third section.

2. The neuro guidewire device of claim 1, wherein a diameter of the second corewire section is less than a diameter of the first corewire section of the third section of the corewire.Attorney Docket No. 00170-0032-003043. The neuro guidewire device of claim 1, wherein the maximum diameter of each of the first section, the second section, the third section, and the fourth section is less than about 0.356 mm.

4. The neuro guidewire device of claim 1, wherein a length of the first section is in a range of about 20 mm to about 70 mm.

5. The neuro guidewire device of claim 1, wherein a length of the second section is in a range of about 20 mm to about 70 mm.

6. The neuro guidewire device of claim 1, wherein a diameter of the coil is about 0.356 mm.

7. The neuro guidewire device of claim 1, wherein at least a portion of the coil that is provided around the first section of the corewire is formed of a radiopaque material.

8. The neuro guidewire device of claim 1, wherein the first section includes a distal-most portion extending that extends at an angle relative to a remainder of the first section, wherein the angle is in a range of about 25° to about 65° and a length of the distal- most portion is in a range of about 1 mm to about 4 mm.

9. A neuro guidewire device for treatment of obstructions within vasculature behind an eye of a subject, the neuro guidewire device comprising: a corewire having a plurality of sections, including: a first section at a distal end of the corewire, the first section being tapered and having a minimum diameter at a distal end of the corewire, and a maximum diameter at a proximal end of the first section: a second section, proximal to the first section, the second section having: a first tapered portion, extending from the proximal end of the first section, and increasing in diameter from a distal end of the first tapered portion to a proximal end of the first tapered portion; andAttomev Docket No. 00170-0032-00304 a second tapered portion, proximal to the first tapered portion, and increasing in diameter from a distal end of the second tapered portion to a proximal end of the second tapered portion; and a third section, proximal to the second section, the third section having a constant diameter; and a coil provided around at least the first section and at least a portion of the second section.

10. The neuro guidewire device of claim 9, wherein the maximum diameter of each of the first section, the second section, and the third section is less than about 0.356 mm.

11. The neuro guidewire device of claim 9, wherein a length of the first section is in a range of about 20 mm to about 70 mm.

12. The neuro guidewire device of claim 9, wherein a length of the second section is in a range of about 20 mm to about 70 mm.

13. The neuro guidewire device of claim 9, wherein a diameter of the coil is about 0.356 mm.

14. The neuro guidewire device of claim 9, wherein the first tapered portion of the second section forms a continuous taper with the first section of the corew ire.

15. The neuro guidewire device of claim 9, wherein at least a portion of the coil that is provided around the first section of the corew ire is formed of a radiopaque material.

16. The neuro guidewire device of claim 9, wherein the first section includes a distal-most portion extending that extends at an angle relative to a remainder of the first section, wherein the angle is in a range of about 25° to about 65° and a length of the distal- most portion is in a range of about 1 mm to about 4 mm.

17. A method of using the neuro guidewire device of claim 1 for treatment of obstructions within vasculature behind an eye of a subject, the method comprising: placing a catheter sheath introducer into the subject; andAttorney Docket No. 00170-0032-00304 placing the neuro guidewire device through the catheter sheath introducer, until a distal end of the neuro guidewire device is positioned at a predetermined location within an ophthalmic artery (OA) of the subject, or distal to the OA.

18. The method of claim 17, wherein placing the neuro guidewire device includes using fluoroscopy to confirm placement of one or more marker bands on the neuro guidewire device at respective predetermined locations within the OA.

19. The method of claim 18, wherein placing the neuro guidewire device includes using fluoroscopy to confirm placement of at least the distal end of the neuro guidewire device at a predetermined location within the OA or distal to the OA.

20. The method of claim 17, further comprising: placing a diagnostic catheter into the subject, before placing the catheter sheath introducer into the subject: and placing a guidewire, different from the neuro guidewire device, within the diagnostic catheter into a common carotid artery (CCA) or an internal carotid artery (ICA) of the subject, before placing the catheter sheath introducer into the subject, wherein placing the catheter sheath introducer includes delivering the catheter sheath introducer over the guidewire, until a distal end of the catheter sheath introducer is positioned within the CCA or the ICA.

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