USING RETROGRADE BLOOD FLOW

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C §1 19(e) of U.S. Provisional Application No. 62/395,294, entitled "Device to Produce a Reverse Flow Ophthalmic Artery Return Circuit," filed September 15, 2016, and U.S. Provisional Application No. 62/396,091 , entitled "Systems and Methods for Treating Eye

Diseases Using Retrograde Blood Flow," filed September 16, 2016, the entirety of each of which is incorporated by reference herein.

TECHNICAL FIELD

[0002] The present disclosure relates to treating an eye, including diseases and other conditions of the eye, using retrograde blood flow. More specifically, the present exemplary embodiments include apparatus and methods for inducing retrograde blood flow in arteries that normally supply blood to the eye, to inhibit embolic debris from traveling to, for example, the brain or the eye.

BACKGROUND

[0003] Diseases of the eye, specifically age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy, affect a large percentage of the population. In the example of AMD, treatments include implanting a lens, drug/antibody injections, and/or photo or laser treatment to destroy "abnormal" blood vessels. However, these therapies are deficient in one or more aspects,

necessitating improved approaches. For example, many eye disease therapies treat one or more symptoms, without addressing the underlying cause(s) of the disease or condition.

[0004] The pathogenesis of some eye diseases and conditions may be similar if not the same as those of cardiac diseases and abdominal aorta conditions.

However, the anatomy of the vasculature behind the eye is typically smaller, includes more branches, and includes more odd angles in the blood flow pathway, e.g., the angle where one artery meets or joins another is sometimes severe. That is, the anatomy of the vasculature behind the eye includes a more tortuous blood flow pathway than the anatomy of the vasculature of the cardiac system and the abdominal aorta.

[0005] Interventions in the cerebral vasculature also often have unique access challenges. Many neurointerventional procedures use a transfemoral access to the carotid or vertebral artery and thence to the target cerebral artery. However, this access route is often tortuous, long, and may contain stenotic plaque material in the aortic arch and carotid and brachiocephalic vessel origins, presenting a risk of embolic complications during the access portion of the procedure. Many

neurointerventional procedures remain either more difficult or impossible because of device access challenges. In some instances, a desired access site is the carotid artery. Procedures in the intracranial and cerebral arteries are much closer to this access site than a femoral artery access site. Importantly, the risk of embolic complications while navigating the aortic arch and proximal carotid and

brachiocephalic arteries are avoided during a procedure having a carotid artery access.

[0006] As an example of an interventional procedure, a carotid

endarterectomy is a surgical procedure in which fatty deposits blocking one of the two carotid arteries are removed to prevent the potential for stroke. The disease process that causes this buildup of material inside the carotid artery is called atherosclerosis, and is often referred to as "hardening of the arteries." The fatty deposits are called plaque, and the narrowing of the artery is called stenosis. The degree of stenosis is usually expressed as a percentage of the normal diameter of the opening (e.g., the diameter of opening without a stenosis). During this procedure, there is a risk of stroke for the patient (also referred to herein as the subject). Stroke may occur if material is dislodged during the endarterectomy and travels up into the brain or beyond. One method for monitoring the potential of stroke is by monitoring High Intensity Transitory Signals (HITS) of the patient. If a stroke occurs it will generate a HITS which is observed during Trans Cranial Doppler Monitoring (TCDM) of the patient. HITS typically detect micro emboli which can be either solid or gas.

[0007] Reverse or retrograde flow may occur when arterial vessels are in fluid communication at two points, e.g. a proximal location and a distal location. When the fluid pressure in one arterial conduit drops, the pressure from the other arterial conduit can cause the blood from the other side to flow into this conduit. For example, the arterial side of the cerebral circulatory system can be seen as divided into two sets of contralateral arteries, both sets originating from the aortic arch with one set feeding the left side of the brain and the other set feeding the right side. A large number of minor and major communicating vessels connect these contralateral arteries. As such, if the blood pressure becomes low enough on a given side, the pressure on the contralateral may be sufficient to cause blood to flow across the communicating vessels and in a retrograde fashion towards the low-pressure source. Artificially and temporarily occluding the natural antegrade flow in a cerebral vessel and providing a low-pressure outlet for the blood can induce this retrograde effect.

[0008] This effect can be particularly useful when treating an artery in or near the cerebral vasculature, or in another vessel with similar contralateral flow properties. Endovascular treatment of a blood vessel, which has a reduced diameter, for example, through the effects of lesions called atheroma or the occurrence of cancerous tumors, can generate free-floating debris. Such debris may cause damaging embolisms, and embolisms occurring in the brain are particularly dangerous. By inducing retrograde flow across a lesion in a cerebral vessel, generated debris can be routed away from the brain or eye, captured in a filter, and removed without the potential to cause damage to organs or in the cerebral vasculature.

[0009] Notwithstanding the usefulness of the above-described methods, a need still exists for a device which can be used to selectively induce reverse blood flow in the cerebral vasculature, particularly any of the arteries supplying blood to or near the eye. The systems, devices, and methods of the current disclosure may rectify some of the deficiencies described above or address other aspects of the prior art.

SUMMARY

[0010] Examples of the present disclosure relate to, among other things, medical devices and related methods. Each of the examples disclosed herein may include one or more of the features described in connection with any of the other disclosed examples.

[0011] In one example, a method of inducing retrograde blood flow may include inserting a first arterial device into at least one of an internal carotid artery and a common carotid artery of a subject. Additionally, the method may include inserting a second arterial device into a terminal branch of an ophthalmic artery of the subject. Further, the method may include inducing retrograde blood flow into the first arterial sheath and delivering at least some of the induced retrograde blood flow through the second arterial device and into the terminal branch of the ophthalmic artery.

[0012] Examples of the method may include any one or more of the following features. Inducing retrograde blood flow may include expanding an occlusion device of the first arterial device. Inducing retrograde blood flow may include compressing the at least one of the internal carotid artery and the common carotid artery against a surface of the first arterial device. The method may further include inserting a vascular device within a vein of the subject. The vein may be an internal jugular vein of the subject. The occlusion device may be a balloon. The induced retrograde blood flow may include retrograde blood flow within the ophthalmic artery of the subject. Inserting at least one of the first arterial device or the second arterial device may include insertion through skin of a face of the subject. Inserting the second arterial device into a terminal branch of the ophthalmic artery of the subject may include insertion within at least one of a supra orbital artery, a supra trochlear artery, a dorsal nasal artery, or a facial artery of the subject.

[0013] In a further aspect, a method of inducing retrograde blood flow may include fluidly coupling a first device located within an arterial system of a subject with a second device located within a venous system of the subject. The method may further include inducing a first flow of blood from an ophthalmic artery of the subject, through the first device, through the second device, and into the venous system of the subject. Additionally, the method may include inducing a second flow of blood through the first device, through a third device located in a terminal branch of the ophthalmic artery of the subject, and into the arterial system of the subject. [0014] Examples of the method may include any one or more of the following features. The method may include treating at least one of the ophthalmic artery and a junction between the internal carotid artery and the ophthalmic artery of the subject. The first device may include an expandable portion on a distal end thereof and the method may further include expanding the expandable portion to impede antegrade blood flow in at least a portion of the arterial system of the subject. The method may include compressing an arterial wall of the arterial system against a surface of the first device. The method may include inserting the first device within the arterial system of the subject via a cervical approach. The method may include inserting the third device in at least one of a supra orbital artery, a supra trochlear artery, a dorsal nasal artery, or a facial artery of the subject.

[0015] In a further aspect, a medical system may include a first arterial sheath including an expandable occlusion device on a distal end thereof and a second arterial sheath configured for insertion into a terminal branch of an ophthalmic artery of a subject. The system may further include a venous sheath and a stopcock. Each of the first arterial sheath, second arterial sheath, and venous sheath may be coupled to the stopcock.

[0016] Examples of the system may further include any one or more of the following features. The expandable occlusion device may be a balloon configured to engage a wall of at least one of a common carotid artery or the internal carotid artery of the subject. A first conduit may extend between the stopcock and the venous sheath, and a second conduit may extend between the stopcock and the second arterial sheath. A filter may be positioned along the first conduit between the stopcock and the venous sheath. The second arterial sheath may be configured for insertion within at least one of a supra orbital artery, a supra trochlear artery, a dorsal nasal artery, or a facial artery of the subject.

[0017] In a further aspect, a system for treating an eye disease, disorder, or condition may include restoring or increasing an amount of blood flow to an eye, an eye portion, or a structure associated with the eye or portion of the eye of a subject. The system may include a transcutaneous intervention device adapted and configured for ocufacial access and entry into vasculature between an internal carotid artery of the eye. [0018] The present disclosure also relates to a method of treating an eye disease or condition by using a device, method, system, or assembly as described herein.

[0019] The present disclosure also relates to a method of restoring or increasing blood flow by using a device, method, system, or assembly as described herein.

[0020] The present disclosure also relates to a method of restoring or increasing nutrients to the eye and/or structures of the eye by using a device, method, system, or assembly as described herein.

[0021] The present disclosure may also include methods, devices, and systems for removing a blockage in the ostium or a proximal segment of the OA near the ICA. In these embodiments, removing the blockage comprises opening a channel or access through the ostium sufficient to provide a therapeutically beneficial result to the eye, the rear of the eye, or portions thereof. The present disclosure also includes restoring and/or improving blood flow anywhere in the vascular pathway to or within the eye.

[0022] Therapeutically beneficial result is used herein to refer to any perceived or actual benefit to the patient. Examples of beneficial results include but are not limited to: treatment of an eye disease, condition, and/or symptom; restoring or increasing blood flow in any manner that treats an eye disease, condition, and/or symptom; and removing or partially removing a blockage in the blood flow path between the heart and the eye, preferably in the ophthalmic artery or a portion thereof.

[0023] The present disclosure also involves restoring or improving blood flow to the eye, thereby altering the complement system. In some embodiments of the disclosure, several CS factors, their activators, and complement regulatory proteins where identified as cardinal constituents of drusen, the hallmark extracellular retinal deposits associated with early AMD. In other embodiments of the disclosure, restoring or improving blood flow reduces or mediates the abnormal concentration of primary complement factors and their activated products in the vasculature of patients suffering from eye diseases such as AMD and glaucoma. [0024] In other embodiments of the disclosure, restoring or improving blood flow to the back of the eye may eliminate, reduce, or mediate CS activation, which directly damages host tissue and recruits immune cells to the vicinity of an active complement cascade. In these and other embodiments, the choroid- and RPE- based regulation of the CS activity has been found to play an important role in the functions of the eye (RPE = retinal pigment epithelium).

[0025] Both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the features, as claimed. As used herein, the terms "comprises," "comprising," "having," "including," or other variations thereof, are intended to cover a non-exclusive inclusion such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such a process, method, article, or apparatus.

Additionally, the term "exemplary" is used herein in the sense of "example," rather than "ideal." As used herein, the terms "about," "substantially," and "approximately," indicate a range of values within +/- 5% of the stated value unless otherwise stated.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the present disclosure and together with the description, serve to explain the principles of the disclosure.

[0027] FIGS. 1A and 1 B illustrate vasculature of the eye of a subject;

[0028] FIG. 2 is a reverse flow system according to an aspect of the present disclosure;

[0029] FIG. 3 is a sheath and flow direction balloon within an internal carotid artery, according to an aspect of the present disclosure; and

[0030] FIG. 4 is a sheath within an internal carotid artery, and a flow direction element about the artery, according to an aspect of the present disclosure. DETAILED DESCRIPTION

[0031] Reference will now be made in detail to examples of the present disclosure described above and illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

[0032] The terms "proximal" and "distal" are used herein to refer to the relative positions of the components of an exemplary medical device or insertion device. When used herein, "proximal" refers to a position relatively closer to the exterior of the body or closer to a medical professional using the medical device or insertion device. In contrast, "distal" refers to a position relatively further away from the medical professional using the medical device or insertion device, or closer to the interior of the body.

[0033] The terms "downstream" or "antegrade" and "upstream" or

"retrograde," when used herein in relation to the subject's vasculature, refer respectively, to the direction of blood flow and the direction opposite that of blood flow, respectively. In the arterial system, "downstream" or "antegrade" refers to the direction further from the heart, while "upstream" or "retrograde" refers to the direction closer to the heart.

[0034] As used herein, "embolic debris" means any biologic or non-biologic mass, the presence of which in the vasculature may present a risk, including, but not limited to, plaque, emboli, etc.

[0035] FIGS. 1 A and 1 B illustrate anatomy relating to an eye of a patient or subject. The vasculature in the fluid flow path to and from the eye, the rear of the eye, portions of the eye, or regions near the eye includes, among other arteries and veins, the internal carotid artery (ICA) 2, the ophthalmic artery (OA) 4, and the junction 6 between the ICA 2 and the OA 4, which is also referred to as the ostium, as shown in FIG. 1 A. In most patients, OA 4 extends at an acute angle relative to ICA 2, as shown in FIGS. 3 and 4. In some patients, a flap of tissue (not shown) may extend between OA 4 and ICA 2. That is, in some arrangements, the flap of tissue may be positioned in junction 6. Additional areas of the anatomy, as shown in FIG. 1 B, may include the vascular system which is commonly referred to as the terminal branches. These areas include, but are not limited to, the supra orbital artery (SOA), the supra trochlear artery (STA), the dorsal nasal artery (DNA), and the facial arteries (FA).

[0036] Diseases and conditions of the eye (e.g., AMD, glaucoma, diabetic retinopathy etc.) may result in decreased blood flow to and around the eye, which is believed to contribute to nutrient (e.g., oxygen) depletion in and around the eye. While not intending to be restricted to any particular theory of operation, function, or causal connection, the inventors believe conditions that lead to lowered oxygen (or other nutrient) delivery to the tissue in and around the eye mediates and/or causes any of a variety of eye diseases, including but not limited to AMD. Possible conditions include but are not limited to one or more of the following: blockage(s) in ICA 2; blockage(s) in OA 4; reduced blood flow anywhere in the fluid flow path between ICA 2 and eye tissue; reduced blood flow rate anywhere in the fluid flow path between ICA 2 and eye tissue; decreased hemoglobin amount or delivery to one or more eye tissues; and blockage(s) or reduced flow in any of the junctions or ostia between any of the vasculature between the ICA 2 and one or more eye tissues (e.g., junction 6).

[0037] According to aspects of the present disclosure, diseases and conditions of the eye may be directly mediated by improved blood flow to the vasculature of the eye (e.g., the posterior of the eye). For example, the systems, devices, and methods described herein may restore or increase the amount of oxygen (or other nutrient) that reaches the eye or an eye area which may include removing or opening a blockage (or partial blockage) in one or more vascular systems that support the eye. Opening a blockage or partial blockage may include increasing or restoring blood flow to or around the eye. Increasing blood flow may include, but is not limited to, increasing the blood flow rate. That is, aspects of the present disclosure may be directed to one or more intravascular medical devices and/or methods intended or configured to sufficiently unblock or at least partially restore blood flow in a blocked or partially blocked artery such that nutrient (e.g., oxygen) content is increased distal to the blockage. For example, in some aspects, the present disclosure is directed to devices and methods for restoring blood flow through the ostium or junction 6.

[0038] In additional aspects, the disclosure is directed to using such devices and methods to restore or increase blood flow and/or or restore or increase nutrient (e.g., oxygen) levels, to the eye or a portion thereof. Restoring or increasing oxygen flow may include using the devices and methods described herein, or equivalent devices and methods, but is not to be limited thereby. Various conditions or diseases of the eye may be treated according to embodiments of the disclosure. Exemplary conditions and diseases are described in U.S. Provisional Patent

Application No. 62/396,091 , entitled "Systems and Methods for Treating Eye

Diseases Using Retrograde Blood Flow," filed September 16, 2016, and incorporated by reference herein in its entirety.

[0039] Exemplary embodiments of the present disclosure provide a reverse flow or retrograde flow device and system for the treatment of an eye, including the treatment of any diseases or conditions of the eye. Such a reverse or retrograde flow may protect the brain or the eye from the possibility of an embolic event or other damage during a cerebral interventional procedure.

[0040] "Reverse flow," as used herein, is the flow of blood opposite to the direction of blood flow under normal blood flow conditions. In this disclosure, "reverse flow" and "retrograde flow" are used synonymously. Reverse flow may be achieved by creating a pressure gradient so blood flow is reversed and directed, for example, from the treatment site into a lumen of a catheter to be rerouted to another location. The pressure gradient can be facilitated by creating a low-pressure source(s), which can be within the catheter itself or created in a desired location within the vasculature that is in fluid communication with the lumen of the catheter.

[0041] Possible "conditions" as used herein may include, but are not limited to, one or more of the following: reduced or blocked blood flow in one or more arteries or system of arteries; reduced or blocked source of energy or nutrients to a cell, organelle of a cell; mitochondrion; group of cells, or organ; altered aerobic energy metabolism; altered mitochondria oxidative phosphorylation; decreased or blocked supply of glucose; decreased hemoglobin amount or delivery to one or more intracranial structures or to one or more eye tissues; reduced blood flow or rate anywhere in the fluid flow path between the ICA and eye tissue; and any blockage or partial blockage in one or more arteries or system of arteries; any mediation of the complement system, the complement cascade, and/or one of the complement cascade associated molecules; and lowered/blocked nutrient supply and/or metabolic waste removal is implicated, and therefore may mediate one or more diseases, disorders, or biological function.

[0042] "Nutrients" as used herein includes but is not limited to oxygen, hemoglobin, complement, and glucose.

[0043] In exemplary embodiments of the present disclosure, the resistance of blood flow through the system from the arterial side to the venous side may be reduced by a cervical approach. In some arrangements, one or more devices or sheaths may be inserted through the skin of a face of a subject. In certain embodiments of reverse flow systems, as will be described below, tubing, stopcocks, hemostasis valves, and blood/particulate filters with large lumens and/or high flow throughput may be used. In some embodiments, the device may be about 8.5 (2.83 mm) to about 9.0 French (3 mm). In addition, the length of the tubing may be minimized, which when combined with larger luminal diameters and high flow blood/particulate filters, may result in reducing resistance to blood flow through the system from the arterial side to the venous side. Certain embodiments, as also described below, include a dedicated circuit to provide for reverse blood flow in the ophthalmic artery during the reverse flow procedure.

[0044] As will be discussed below in connection with the figures, a reverse flow system according to an exemplary embodiment may include some or all of the following components: two percutaneous sheaths (including a first arterial sheath and a second venous sheath); intravenous tubing with a low flow resistance blood/particulate filter and connecting the sheaths between the arterial and venous sheath access points; two stopcocks, a first stopcock containing a hemostasis valve on the arterial side of the blood filter near the arterial sheath; and a third sheath inserted into one of the terminal branches of the ophthalmic artery, and connected via a hemostasis valve to the intravenous tubing. The tubing is connected to a port of the stopcock attached to the arterial sheath. This exemplary arrangement represents a separate circuit which takes blood from the arterial sheath and feeds it into a terminal branch of the ophthalmic artery thereby inducing reverse flow in the ophthalmic artery. Additional components may include, on the venous side of the blood filter, a single stopcock. The stopcocks may be designed to maximize the luminal diameter such that resistance to blood flow from the arterial side to venous side of the system is minimized. Minimizing the blood flow resistance of the system will maximize the speed and ability of the system to remove potential embolic material from the artery under reverse flow and return arterial blood to the venous system.

[0045] In one exemplary embodiment shown in FIG. 2, a flow reversal system 10 includes: (i) an arterial sheath 20 having proximal and distal ends with a lumen extending therethrough; (ii) a venous sheath 30 having proximal and distal ends with a lumen extending therethrough; (iii) an expandable occluder 60 at the distal end of arterial sheath 20; (iv) a venous return circuit 21 at or near a distal end of sheath 20 proximal to expandable occluder 60; (v) a conduit 40, with a particulate/blood filter 45 interspersed, fluidly connecting a proximal opening of arterial sheath 20 to the venous sheath 30; and (vi) a circuit 50 connecting an arterial sheath stopcock 22 with a terminal branch of OA 4 (while the supra trochlear artery is depicted in FIG. 2, any other terminal branch/vessel downstream from OA 4 may be used) via a sheath 52. Arterial sheath 20 is placed in the common carotid artery (CCA), though it could be placed in ICA 2, and the venous sheath is placed in the internal jugular vein (IJV), though other venous vessels may be used. A pressure gradient is created so that blood flows into the distal opening of arterial sheath 20, through conduit 40, and exits through a return port into the venous sheath 30. Flow reversal system 10 may be cervically-placed. Additionally, as shown in FIG. 2, arterial sheath 22 may further include an additional stopcock 23, venous sheath 30 may include a venous stopcock 31 , and sheath 52 may include a stopcock 51 .

[0046] An additional connection to the arterial sheath 20 includes circuit 50 that connects to sheath 52 placed in a terminal artery of OA 4 such that a portion of blood flow from the arterial sheath 20 is sent through circuit 50 and into the terminal artery of OA 4 for the purpose of reversing flow in OA 4, other arteries, and/or other arteries that supply blood to the eye.

[0047] Blocking the flow of blood facilitates the reversal of blood flow across a treatment site. By way of example, expanding expandable occluder 60 in the common carotid artery blocks the flow through the common carotid artery and causes the pressure on the downstream side, i.e., distal side of expandable occluder 60, to drop, thereby facilitating blood from contralateral vessels to flow toward the lower pressure and flow into arterial sheath 20, which carries embolic debris into the blood/particulate filter 45. [0048] The expandable occluder 60 can be any shape which occludes a radial space about the distal region or end of the arterial sheath 20, so as to ensure blood and emboli is directed into the distal opening of the arterial sheath 20, rather than becoming trapped between an intraluminal wall of the blood vessel and an outer wall of arterial sheath 20. For example, expandable occluder 60 can be disc-shaped, donut-shaped, cylindrical, cone-shaped, funnel-shaped, or any other shape that substantially occludes the flow of blood about the radial space of the distal region of the arterial sheath 20 and defines the outer wall of the arterial sheath 20 to permit blood to pass through the distal opening of the arterial sheath 20. FIG. 3 shows a cross section of the placement and structure of a flow direction balloon 60' in the ICA 2, which is an alternative to placement in the CCA. As shown, flow direction balloon 60' may include a tapered cylinder or cone shaped balloon having a proximal end coupled to a distal end of arterial sheath 20 and may guide or otherwise facilitate a flow of blood through arterial sheath 20. That is, a wall or surface of balloon 60' may narrow towards a distal end of arterial sheath 20, and contact a wall of ICA 2 at distal portions of balloon 60'.

[0049] Embodiments of the present disclosure also include a retrograde flow system that does not require the use of a balloon or the like. In these systems, methods, and assemblies, the flow direction element applies an external force applied to an artery to compress the artery around the sheath 20. Such an embodiment is shown in FIG. 4, where the external force is provide by a clamp 62.

[0050] Embodiments of the present disclosure include any tool or device that functions to apply force, to clamp or close the artery against sheath 20. Exemplary elements include but are not limited to a clamp, a vise, a band, a suture, a pincer, a contractor, a constrictor, and the like. In function, any such element compresses or closes the artery against the sheath 20, thereby forcing any blood flow through the lumen of sheath 20 rather than around sheath 20.

[0051] Thus, in embodiments of this disclosure, the flow direction element of the system is used to initiate the reversal of flow in the CCA (or the ICA 2).

Typically, flow reversal may be accomplished by use of an occluder 60, an inflatable balloon device such as, e.g., balloon 60'. As described, flow reversal may also be accomplished without a balloon by using a sheath that has external force applied to compress the CCA/ICA 2 against the tube portion of the arterial sheath 20. This compressive action serves to prevent blood flow around the arterial sheath 20 (in the same way as an inflatable balloon does from inside the CCA/ICA 2) and force blood through the arterial sheath 20 and into the venous circuit of the system, thereby providing flow reversal. The sheath may be of conventional design, or may contain elements that facilitate compressing the CCA/ICA against the arterial sheath 20 for the purpose of establishing flow reversal. These elements may include the following: (1 ) specific arterial sheath 20 durometer material design to accommodate

compressive force while maintaining arterial sheath 20 lumen integrity; (2) radiopacity elements incorporated into the arterial sheath 20 to allow for confirmation of proper clamping position via fluoroscopy; and/or (3) incorporation of a distal sheath inflatable element (e.g., occluder 60 and/or balloon 60') to aid in the direction of blood flow into the arterial sheath 20 lumen and to prevent blood leakage between the arterial sheath 20 and the CCA/ICA 2 during clamping.

[0052] In another embodiment of this disclosure, the arterial access device may include a catheter or sheath 20 having a backstop (e.g., balloon 60'); and a central guidewire (not shown) for passing through a lumen of the sheath 20. The guidewire includes an attached inflatable balloon, and a knot, brush, or other geometrically shaped artherectomy-like element extending outwardly on the guidewire, distally of the balloon. In use, the element may be deployed in the region of a plaque or obstruction to loosen particles in the artery, which flow back toward sheath 20. The guidewire balloon may then be partially inflated/deployed, whereby particles may become trapped between the balloon and the end of the sheath 20 and balloon 60'. The guidewire balloon then may be drawn back into the sheath 20, thereby drawing and capturing particles within the lumen of the sheath 20. The sheath 20, carrying the particles, then may be pulled out of the body and/or the particles may be aspirated out of sheath 20.

[0053] Alternatives of this just-described embodiment may include a guidewire with a distal tip comprising a kite tail shaped element; a backstop comprising a funnel shaped cage; and/or a balloon that is deployed and/or expanded in stages, e.g., the proximal end first, thereby forcing, pushing, or capturing particles into the backstop. Additional interventional procedures and devices are described below and in U.S. Provisional Patent Application No. 62/396,091 , entitled "Systems and

Methods for Treating Eye Diseases Using Retrograde Blood Flow," filed September 16, 2016, and incorporated by reference herein in its entirety, and International Application PCT/US2017/021673, entitled "Systems and Methods for Treating Eye Diseases Using Retrograde Blood Flow," filed March 9, 2017, and incorporated by reference herein in its entirety.

[0054] As mentioned above, a purpose of reverse flow is to channel embolic debris of a wide range of particle sizes away from particularly at-risk areas during an endovascular treatment. In accordance with an embodiment, blood, along with embolic debris in some embodiments, from the treatment site is rerouted through a sheath/catheter to another location, for example from high to low pressure. A filter (e.g., filter 45) can be included to capture embolic debris from the blood. Once the blood passes through the filter, the blood may be re-introduced into the venous circulation.

[0055] Embodiments of this disclosure include methods of achieving reverse flow in cerebral vasculature, and, in exemplary embodiments, in the OA 4 and ICA 2. Prior to performing the method, a duplex ultrasonography scan may be performed to measure the distance between the planned puncture site and the carotid bifurcation and also to confirm the anatomical status of the common carotid artery.

[0056] To reverse the blood flow, the following steps may be taken:

[0057] 1 ) A small 4 cm transverse incision is made at the base of the neck between the two heads of the sternocleidomastoid muscle. The common carotid artery is dissected free for about two centimeters, as well as the internal jugular vein. A vessel loop is placed around either vessel.

[0058] 2) A 9 Fr venous sheath, e.g., sheath 30, is inserted in the caudal direction over a wire after puncturing the jugular vein.

[0059] 3) An arterial sheath 20 is inserted in the CCA in a cephalad direction using a guidewire. The arterial sheath 20 has a stopcock 22 attached to the proximal end of the arterial sheath 20. The guidewire may be a stiff 0.035" guidewire introduced in the external carotid artery under fluoroscopic.

[0060] 4) An additional, appropriately sized arterial sheath (e.g., sheath 52) is inserted into a terminal artery of OA 4 and connected via intravenous tubing (e.g., circuit 50) to the arterial sheath stopcock 22. [0061] 5) The three-way-stopcock 22 is opened to allow the blood to fill the tubing or conduit 40 and the filter 45. The stopcock of the arterial line is opened and then, after flushing blood, is connected to the venous tubing establishing the fistula.

[0062] 6) The occluding element (e.g., balloon 60) on the distal tip of the large lumen arterial sheath 20 is inflated in the common carotid artery. At this moment, flow reversal is established, and the OA 4 sheath 52 stopcock 51 is opened to establish reverse flow in the OA 4 circuit. A small injection of contrast media through the side-port of the arterial sheath will confirm that flow is reversed.

[0063] According to this method, a temporary, reversible arterio-venous fistula can be created between the common carotid artery (or the ICA 2) and the jugular vein at the base of the neck through, for example, a small incision done under local anesthesia. The fistula produces a temporary reversal of flow of the internal carotid artery or the OA 4, which may itself unblock the OA 4, or while an interventional procedure may be performed. This flow reversal allows particulate to be removed from the bloodstream during an intervention procedure, to not pose a cerebral or eye embolic threat or damage.

[0064] After creating the fistula, the operator may commence an interventional procedure. The interventional procedure may include providing one or more stents implanted in the vasculature supplying blood to the eye. For example, a stent may be placed in ICA 2, OA 4, or at the ostium or junction 6 of ICA 2/OA 4. The stent may provide patency. The stent may include radiopaque features to guide in accurate placement. Other interventional procedures may include use of a balloon in an angioplasty-like procedure, or performing an atherectomy. These procedures may restore and/or increase the amount of oxygen (or other such nutrients) being delivered to the eye. Devices, methods, therapies, or combinations that change the oxygen (or other nutrient) content in or near the eye include, but are not limited to, increasing the blood flow anywhere in the vasculature leading to the eye or a portion of the eye; removing or opening an obstruction in the fluid flow path in the

vasculature leading to the eye; delivering and deploying a stent in the fluid flow path in the vasculature leading to the eye; using atherectomy or similar devices to physically remove portions of any obstructions in the vasculature leading to the eye or portion of the eye; and localized drug and/or an oxygen device for increasing flow or amount of oxygen in one or more eye tissues. In some embodiments, a device or method of the present disclosure may be combined with a known or new drug or oxygen device in order to treat one or more eye diseases or conditions. The present disclosure provides for an apparatus for deployment of a detachable diagnostic or therapeutic implant device such as a stent, embolic coil, or other vascular occlusion device using a catheter, whereby placement of a stent or the like in a portion of the carotid artery changes the diameter of the ICA 2 and/or OA 4, which in turn increases blood flow between the ICA 2 and the eye.

[0065] Exemplary interventional procedures, and implants, catheters, guidewires, balloons, and other therapeutic devices for use in interventional procedures, according to embodiments of this disclosure, are described in the following documents, each of which is incorporated by reference in its entirety: U.S. Provisional Patent Application No. 62/396,091 , entitled "Systems and Methods for Treating Eye Diseases Using Retrograde Blood Flow," filed September 16, 2016; and U.S. Patent Application No. 15,609,547, entitled "Devices and Methods for Treating Occlusion of the Ophthalmic Artery, filed May 31 , 2017.

[0066] It is intended that this disclosure should not be limited by the type of procedure (cervical) or use of specific instruments necessary to provide an interventional result. For example, in accordance with this disclosure, eye disease may be treated using at least one arterial access device, using a percutaneous transfemoral approach; a transcervical approach; cervical access; or combinations thereof. Exemplary access procedures and devices are described in U.S.

Provisional Patent Application No. 62/396,091 , entitled "Systems and Methods for Treating Eye Diseases Using Retrograde Blood Flow," filed September 16, 2016, and incorporated by reference herein in its entirety.

[0067] In accordance with this disclosure, a reverse flow system may be established in any location suitable for treating an eye disease or condition. These locations include but are not limited to the ICA 2, the external carotid artery, the common carotid artery, the supraorbital artery, the supra-trochlear artery, the OA 4; and an appropriate site in the venous system, including but not limited to the internal jugular vein or the femoral vein. [0068] In accordance with this disclosure, an eye disease or condition may include but are not limited to one or more of the following: reduced or blocked blood flow in one or more arteries or system of arteries; reduced or blocked source of energy or nutrients to a cell, organelle of a cell; mitochondrion; group of cells, or organ; altered aerobic energy metabolism; altered mitochondria oxidative

phosphorylation; decreased or blocked supply of glucose; altered aerobic energy metabolism; photoreceptor dysfunction and degeneration; altered energy

homeostasis; glucose; glucose and oxygen; mitochondrial damage; one or more combinations of substrates, including but not limited to glucose, pyruvate, lactate, L- glutamine, and β-hydroxybutyrate; altered mitochondria oxidative phosphorylation; complement; any molecule in the complement cascade; and localized drug and/or an oxygen device for increasing flow or amount of oxygen in one or more eye tissues; decreased hemoglobin amount or delivery to one or more intra-cranial structures or to one or more eye tissues; reduced blood flow or rate anywhere in the fluid flow path between the ICA and eye tissue; reduced or blocked blood flow or rate anywhere in the fluid flow path between the ventricle and eye tissue; and any blockage or partial blockage in one or more arteries or system of arteries; any mediation of the complement system, the complement cascade, and/or one of the complement cascade associated molecules; and lowered/blocked nutrient supply and/or metabolic waste removal is implicated, and therefore may mediate one or more diseases, disorders, or biological function.

[0069] Examples of diseases and conditions include, but are not limited to, any of a variety of eye diseases, including but not limited to AMD (both dry and wet); neuronal cell death; Alzheimer's disease; dementia; glaucoma; diabetic macula edema, macular telangiectasia (e.g., type 1 or 2 macular telangiectasia), atrophic macular degeneration, chorioretinopathy (e.g., central serous chorioretinopathy), retinal inflammatory vasculopathy, pathological retinal angiogenesis, age-related maculopathy, retinoblastoma, Pseudoxanthoma elasticum, a vitreoretinal disease, choroidal sub-retinal neovascularization, central serous chorioretinopathy, ischemic retinopathy, hypertensive retinopathy or diabetic retinopathy (e.g., nonproliferative or proliferative diabetic retinopathy, such as macular edema or macular ischemia), retinopathy of prematurity (e.g., associated with abnormal growth of blood vessels in the vascular bed supporting the developing retina), venous occlusive disease (e.g., a retinal vein occlusion, branch retinal vein occlusion or central retinal vein occlusion), arterial occlusive disease (e.g., branch retinal artery occlusion (BRAO), central retinal artery occlusion or ocular ischemic syndrome), central serous

chorioretinopathy (CSC), cystoid macular edema (CME) (e.g., affecting the central retina or macula, or after cataract surgery), retinal telangiectasia (e.g., characterized by dilation and tortuosity of retinal vessels and formation of multiple aneurysms, idiopathic JXT, Leber's miliary aneurysms, or Coats' disease), arterial

macroaneurysm, retinal angiomatosis, radiation-induced retinopathy (RI RP), or rubeosis iridis (e.g., associated with the formation of neovascular glaucoma, diabetic retinopathy, central retinal vein occlusion, ocular ischemic syndrome, or chronic retinal detachment); distortions and/or blind spots (scotoma); changes in dark adaptation (diagnostic of rod cell health); changes in color interpretation (diagnostic of cone cell health); decrease in visual acuity; cataract (e.g., age-related cataract).

[0070] While principles of the present disclosure are described herein with reference to illustrative embodiments for particular applications, it should be understood that the disclosure is not limited thereto. Those having ordinary skill in the art and access to the teachings provided herein will recognize additional modifications, applications, embodiments, and substitution of equivalents all fall within the scope of the embodiments described herein. Accordingly, the disclosure is not to be considered as limited by the foregoing description.