Device for subretinal administration of therapeutic agents via a double-curved needle

Abstract

The device includes a body, a flexible cannula, and a needle. The cannula is sized and configured to advance between the sclera and choroid of a patient's eye. The needle is slidably disposed within the cannula and includes a sharp distal tip. The needle translates relative to the cannula between a proximal position and a distal position. When the needle is in the proximal position, the distal tip is located inside the cannula. When the needle is in the distal position, the distal tip is located outside the cannula. The needle is resiliently biased to extend along at least one proximal curve through at least one proximal curved needle section. The needle is resiliently biased to extend along at least one distal curve through at least one distal curved needle section. The at least one distal curve is different from the at least one proximal curve.

Description

[Background technology]

[0001] background The human eye comprises several layers. The white outer layer is the sclera, which surrounds the choroid layer. The retina lies inside the choroid layer. The sclera contains collagen and elastic fibers and protects the choroid and retina. The choroid layer contains the vasculature, which provides oxygen and nutrients to the retina. The retina contains light-sensitive tissue, including rods and cones. The macula is located in the center of the retina at the back of the eye and is generally centered on an axis (i.e., the optical axis) that passes through the center of the eye's lens and cornea. The macula provides central vision, particularly via cone cells.

[0002] Macular degeneration is a medical condition affecting the macula, such that people with macular degeneration may experience loss or deterioration of central vision while retaining some peripheral vision. Macular degeneration can be caused by various factors, such as aging (also known as "AMD") and genetics. Macular degeneration can occur in a "dry" (non-exudative) form, in which cellular debris known as drusen accumulates between the retina and choroid, resulting in areas of geographic atrophy. Macular degeneration can also occur in a "wet" (exudative) form, in which blood vessels grow from the choroid behind the retina. Even though people with macular degeneration may retain some peripheral vision, loss of central vision can have a significant negative impact on quality of life. Furthermore, the quality of the remaining peripheral vision may be reduced and even eliminated. Therefore, it may be desirable to provide a treatment for macular degeneration to prevent or reverse vision loss caused by macular degeneration. In some cases, it may be desirable to provide such treatment in a highly localized manner, such as by delivering therapeutic agents to the subretinal layers (below the neurosensory layer of the retina and above the retinal pigment epithelium) immediately adjacent to the area of ​​geographic atrophy near the macula. However, because the macula is at the back of the eye and beneath the delicate layers of the retina, it can be difficult to access the macula in a practical manner.

[0003] Although various surgical methods and instruments have been made and used to treat the eye, it is believed that no one prior to the present inventors has made or used the present invention as set forth in the appended claims. [Brief explanation of the drawings]

[0004] While this specification concludes with claims particularly pointing out and distinctly claiming this technology, it is believed that this technology will be better understood from the following description of specific examples taken in conjunction with the accompanying drawings, in which like reference numerals identify the same elements and in which:

[0005] [Figure 1] FIG. 1 shows a perspective view of an example of an apparatus for subretinal administration of a therapeutic agent from a suprachoroidal approach.

[0006] [Figure 2] 2 shows a perspective view of the distal portion of the cannula of the instrument of FIG. 1.

[0007] [Figure 3] 3 shows a front view of the distal portion of the cannula of FIG. 2.

[0008] [Figure 4] 3 shows a top view of the distal portion of the cannula of FIG. 2.

[0009] [Figure 5] 3 shows a perspective view of the distal end of the cannula of FIG. 2 with a needle extending from the cannula.

[0010] [Figure 6] 2 shows a perspective view of the device of FIG. 1 worn near a patient with a combination of medical devices.

[0011] [Figure 7A] 1 shows a cross-sectional side view of a patient's eye.

[0012] [Figure 7B] 7B shows a side cross-sectional view of the eye of FIG. 7A with a suture loop attached to the eye and a sclerotomy performed.

[0013] [Figure 7C] 7B shows a side cross-sectional view of the eye of FIG. 7A with the cannula of FIG. 2 inserted between the sclera and choroid of the eye through a sclerotomy opening.

[0014] [Figure 7D] 7B shows a cross-sectional side view of the eye of FIG. 7A with the distal end of the cannula positioned adjacent to the target location.

[0015] [Figure 7E] 7B shows a side cross-sectional view of the eye of FIG. 7A with the needle of FIG. 5 advanced through the choroid to access the subretinal space at the target location.

[0016] [Figure 7F] 7A shows a cross-sectional side view of the eye of FIG. 7A in which the needle of FIG. 5 dispenses a first volume of leading bleb fluid to create separation between a region of the retina and the choroid at a target location.

[0017] [Figure 7G] 7B shows a side cross-sectional view of the eye of FIG. 7A, in which the needle of FIG. 5 dispenses a therapeutic agent between a region of the retina and the choroid at a target location.

[0018] [Figure 8] 1. FIG. 4 shows a perspective view of an alternative cannula that may be incorporated into the instrument of FIG. 1, the cannula having a varying stiffness along the length of the cannula.

[0019] [Figure 9] FIG. 9 shows a front view of the cannula of FIG. 8.

[0020] [Figure 10] FIG. 9 shows a side view of the cannula of FIG. 8.

[0021] [Figure 11] FIG. 9 shows a top view of the cannula of FIG. 8.

[0022] [Figure 12] 12 shows a cross-sectional view of the intermediate segment of the cannula of FIG. 8 taken along line 12-12 of FIG. 11.

[0023] [Figure 13] 13 shows a cross-sectional view of the distal segment of the cannula of FIG. 8 taken along line 13-13 of FIG. 11.

[0024] [Figure 14] 1. FIG. 4 shows a perspective view of another alternative cannula that may be incorporated into the instrument of FIG. 1, the cannula having a varying stiffness along the length of the cannula.

[0025] [Figure 15] 15 shows a front view of the cannula of FIG. 14.

[0026] [Figure 16] 15 shows a side view of the cannula of FIG. 14.

[0027] [Figure 17] 15 shows a top view of the cannula of FIG. 14.

[0028] [Figure 18] 18 shows a cross-sectional side view of the cannula of FIG. 14 taken along line 18-18 of FIG. 17.

[0029] [Figure 19] 19 shows a cross-sectional view of the proximal segment of the cannula of FIG. 14 taken along line 19-19 of FIG. 17.

[0030] [Figure 20] 17 shows a cross-sectional view of the intermediate segment of the cannula of FIG. 14 taken along line 20-20 of FIG.

[0031] [Figure 21] 21 shows a cross-sectional view of the intermediate segment of the cannula of FIG. 14 taken along line 21-21 of FIG. 17.

[0032] [Figure 22] 22 shows a cross-sectional view of the distal segment of the cannula of FIG. 14 taken along line 22-22 of FIG. 17.

[0033] [Figure 23] 2 shows a side view of an alternative needle that may be incorporated into the device of FIG. 1, the needle having a proximal curve and a distal curve.

[0034] [Figure 24] 24 shows a side view of the distal end of the needle of FIG. 23.

[0035] [Figure 25] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having a proximal curve and a distal curve.

[0036] [Figure 26] 26 shows a side view of the distal end of the needle of FIG. 25.

[0037] [Figure 27] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having a proximal curve and a distal curve.

[0038] [Figure 28] 28 shows a side view of the distal end of the needle of FIG. 27.

[0039] [Figure 29] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having first and second proximal curves and a distal curve.

[0040] [Figure 30] 30 shows a side view of the distal end of the needle of FIG. 29.

[0041] [Figure 31] 30 shows a side view of the needle of FIG. 29 showing the first reference circle of the first proximal curve.

[0042] [Figure 32]30 shows a side view of the needle of FIG. 29 showing the second reference circle of the second proximal curve.

[0043] [Figure 33] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having first and second distal curves.

[0044] [Figure 34] FIG. 34 shows a side view of the distal end of the needle of FIG. 33.

[0045] [Figure 35] FIG. 34 shows a side view of the needle of FIG. 33 showing the reference circle of the first distal curve.

[0046] [Figure 36] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having a proximal curve and first and second distal curves.

[0047] [Figure 37] FIG. 37 shows a side view of the distal end of the needle of FIG. 36.

[0048] [Figure 38] 10 shows a side view of another alternative needle that may be incorporated into the device of FIG. 1, the needle having first and second proximal curves and first and second distal curves.

[0049] [Figure 39] FIG. 39 shows a side view of the distal end of the needle of FIG. 38.

[0050] The drawings are not intended to be limiting in any way, and it is contemplated that various embodiments of the technology may be embodied in a variety of other ways, including those not necessarily shown in the drawings. The accompanying drawings, which are incorporated in and form a part of this specification, illustrate several aspects of the technology and, together with the description, serve to explain the principles of the technology. It will be understood, however, that the technology is not limited to the precise arrangements shown. DETAILED DESCRIPTION OF THE INVENTION

[0051] Detailed Description The following description of specific examples of the present technology should not be used to limit its scope. Other examples, features, aspects, embodiments, and advantages of the present technology will become apparent to those skilled in the art from the following illustrative description of one of the best modes contemplated for carrying out the present technology. As will be understood, the technology described herein is capable of other different and obvious modes, all without departing from the technology. Therefore, the drawings and descriptions should be considered as illustrative in nature and not restrictive.

[0052] It is further understood that any one or more of the teachings, expressions, embodiments, examples, etc. described herein may be combined with any one or more of the other teachings, expressions, embodiments, examples, etc. described herein. Accordingly, the teachings, expressions, embodiments, examples, etc. described below should not be viewed in isolation relative to one another. Various suitable ways in which the teachings herein may be combined will be readily apparent to those skilled in the art in light of the teachings herein. Such modifications and variations are intended to be included within the scope of the following claims.

[0053] For clarity of disclosure, the terms "proximal" and "distal" are defined herein relative to a surgeon or other operator holding a surgical instrument having a distal surgical end effector. The term "proximal" refers to the location of an element closer to the surgeon or other operator, and the term "distal" refers to the location of an element closer to the surgical end effector of the surgical instrument and further away from the surgeon or other operator.

[0054] Furthermore, the terms "about," "approximately," and the like, as used herein in connection with any numerical value or range of values, are intended to encompass the exact value referenced, as well as an appropriate tolerance that enables the referenced feature or combination of features to function for the intended purpose described herein.

[0055] I. Devices for subretinal administration of therapeutic agents

[0056] 1 shows an example of an instrument (100) configured for use in a procedure for subretinal administration of a therapeutic agent to a patient's eye via a suprachoroidal approach. The instrument (100) includes a body (110) and a flexible cannula (130) extending distally from the body (110). The cannula (130) in this example has a generally rectangular cross-section, although any other suitable cross-sectional profile (e.g., oval, etc.) may be used. The generally rectangular cross-sectional profile of the cannula (130) is configured to allow the cannula (130) to pass atraumatically along the suprachoroidal space, as described in more detail below. The cannula (130) is generally configured to support a slidable needle (150) within the cannula (130), as described in more detail below.

[0057] In this embodiment, the cannula (130) comprises a flexible material such as polyether block amide (PEBA), although any other suitable material or combination of materials may be used. In some versions, the cannula (130) has cross-sectional profile dimensions of approximately 1.6 mm (width) by approximately 0.6 mm (height) and a length of approximately 80 mm. Alternatively, any other suitable dimensions may be used. The cannula (130) of this embodiment is flexible enough to conform to the particular anatomy and contours of a patient's eye, yet has sufficient column strength to allow advancement of the cannula (130) between the sclera and choroid of the patient's eye without buckling. As best seen in Figures 2-5, the cannula (130) includes a laterally oriented opening (134) near the distal end (132) of the cannula (130). The opening (134) in this example is formed by a U-shaped lateral recess (136) in the cannula (130) that leads to the open distal end (138) of a needle guide lumen in the cannula (130). The distal end (132) is atraumatic such that the distal end (132) is configured to effect separation between the scleral and choroidal layers via blunt dissection, as described in more detail below, thereby allowing the cannula (130) to be advanced between such layers without trauma to the scleral or choroidal layers.

[0058] By way of example only, cannula (130) may be configured and operable in accordance with at least some of the teachings of U.S. Pat. No. 10,226,379, issued March 12, 2019, entitled "Method and Apparatus for Subretinal Administration of Therapeutic Agents," the disclosure of which is incorporated herein by reference in its entirety, and U.S. Pat. No. 10,646,374, issued May 12, 2020, entitled "Apparatus and Method for Forming an Entry Bleb for Subretinal Delivery of Therapeutic Agents," the disclosure of which is incorporated herein by reference in its entirety and / or in any other suitable manner.

[0059] As shown in FIG. 5, the needle (150) may be advanced distally and protrude from the opening (134). The needle (150) in this example has a sharpened distal tip (152) and defines a lumen (not shown). The distal tip (152) in this example has a lancet configuration. In some other versions, the distal tip (152) has a tribevel configuration or any other configuration, such as that described in U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. Still other suitable forms that the distal tip (152) may take will be apparent to those skilled in the art in view of the teachings herein. In this embodiment, as described in more detail below, when the cannula (130) is positioned within the suprachoroidal space, the generally rectangular, oval, or otherwise generally flat cross-sectional shape of the cannula (130) prevents the cannula (130) from rotating about its longitudinal axis, as described in more detail below. This provides a consistent and predictable orientation of the opening (134), thereby providing a consistent and predictable exit path for the needle (150) as it advances distally relative to the cannula (130).

[0060] By way of example only, after needle 150 is advanced distally relative to cannula 130, the angle defined between the exposed portion of needle 150 and cannula 130 may be in the range of about 5° to about 30° relative to the longitudinal axis of cannula 130, or more specifically, in the range of about 5° to about 20° relative to the longitudinal axis of cannula 130, or more specifically, in the range of about 5° to about 10° relative to the longitudinal axis of cannula 130, and even more specifically, in the range of about 7° to about 9° relative to the longitudinal axis of cannula 130. In this embodiment, needle 150 is resiliently biased into a bent configuration, thereby providing an exit angle that varies based on the extent to which needle 150 is advanced distally relative to cannula 130. By way of further example only, needle (150) may include a preformed bend in accordance with at least some of the teachings of U.S. Patent No. 10,478,553, entitled "Subretinal Therapeutic Agent Administration Device Using a Curved Needle," issued November 19, 2019, the disclosure of which is incorporated herein by reference in its entirety.

[0061] As shown in FIG. 1 , the instrument (100) of the present example further includes an actuation knob (120) disposed on the top portion (114) of the body (110). The actuation knob (120) is rotatable relative to the body (110) to selectively translate the needle (150) longitudinally relative to the cannula (130). In particular, the actuation knob (120) is rotatable in a first angular direction to drive the needle (150) distally relative to the cannula (130) and in a second angular direction to drive the needle (150) proximally relative to the cannula (130). By way of example only, the instrument (100) may provide such functionality via the knob (120) in accordance with at least some of the teachings of U.S. Pat. No. 10,646,374, the disclosure of which is incorporated herein by reference in its entirety. Other suitable manners by which rotational movement of knob (120) can be translated into linear movement of needle (150) will be apparent to those skilled in the art in view of the teachings herein. Similarly, other suitable manners by which needle (150) can be longitudinally actuated relative to cannula (130) will be apparent to those skilled in the art in view of the teachings herein. As also shown in FIG. 1 , conduit assembly (140) extends proximally from body (110). Conduit assembly (140) is configured to house one or more fluid conduits (not shown) that are in fluid communication with needle (150). In some versions, such fluid conduits are coupled to sources of primary bleb fluid and therapeutic agent.

[0062] II. Technique for delivering therapeutic agents to the subretinal space from the suprachoroidal approach

[0063] FIG. 6 illustrates a scenario in which the device (100) is positioned relative to a patient. In this example, a drape (12) is placed over the patient, and an opening (18) is formed in the drape (12) near the patient's eye (301). A speculum (16) is used to hold the eye (301) open. A retainer (14) is placed adjacent to the eye (301). The retainer (14) may be used to secure an instrument, such as a viewing scope, relative to the patient. A magnetic pad (30) is adhered to the drape (12) near the opening (18) adjacent the eye (301). The device (100) is placed on the magnetic pad (30) and removably secured thereto via magnetic attraction. In this example, one or more permanent magnets (not shown) are placed within the body (110) near the bottom (112), and these magnets are magnetically attracted to one or more iron elements (not shown) contained within the magnetic pad (30). By way of example only, these magnets and magnetic pads (30) may be configured in accordance with at least some of the teachings of U.S. Patent No. 10,806,629, issued October 20, 2020, and entitled "Injection Device for Subretinal Delivery of Therapeutic Agents," the disclosure of which is incorporated herein by reference in its entirety. The instrument (100) is oriented to allow insertion of the flexible cannula (130) of the instrument (100) into the eye (301). An example of a process for inserting and positioning the cannula (130) into the eye (301) is described in more detail below with reference to Figures 7A-7F.

[0064] In this example, instrument 100 is coupled to fluid delivery system 80 via conduit assembly 140. In this example, fluid delivery system 80 includes bleb fluid source 82 and therapeutic agent fluid source 84. Bleb fluid source 82 is coupled to bleb fluid conduit 142 of conduit assembly 140, and therapeutic agent fluid source 84 is coupled to therapeutic agent conduit 144 of conduit assembly 140. Conduits 142, 144 are in fluid communication with needle 150. In some versions, fluid sources 82, 84 include syringes. In some other versions, fluid sources 82, 84 include separate reservoirs and one or more associated pumps, valves, and / or the like.

[0065] 7A-7G illustrate an example of a procedure that may be performed using the aforementioned device to deliver a therapeutic agent to the subretinal space (301) of the eye from a suprachoroidal approach. By way of example only, the methods described herein may be used to treat macular degeneration and / or other ocular conditions. While the procedures described herein are discussed in the context of treating age-related macular degeneration, no such limitation is intended or implied. For example, in some alternative procedures, the same techniques described herein may be used to treat retinitis pigmentosa, diabetic retinopathy, and / or other ocular conditions. Furthermore, the procedures described herein may be used to treat either dry or wet age-related macular degeneration, among other conditions.

[0066] In this example, the procedure begins by the surgeon immobilizing the tissue surrounding the patient's eye (301) (e.g., the eyelid) using an instrument such as a speculum (16) and / or any other instrument suitable for immobilization. During the immobilization described herein with respect to the tissue surrounding the eye (301), the eye (301) itself may remain free to move. Once the tissue surrounding the eye (301) is immobilized, an eye chandelier port (314) is inserted into the eye (301), as shown in FIG. 7A , to provide intraocular illumination when viewing the interior of the eye (301) through the pupil. In this example, the eye chandelier port (314) is positioned in the inferior medial quadrant so that a superior temporal sclerotomy can be performed. The eye chandelier port (314) is positioned to direct light into the interior of the eye (301) to illuminate at least a portion of the retina (308) (e.g., including at least a portion of the macula). As will be appreciated, such illumination corresponds to the area of ​​the eye (301) that is targeted for delivery of the therapeutic agent.

[0067] In this example, at the stage shown in FIG. 7A , the optical fiber 315 has not yet been inserted into the port 314; only the chandelier port 314 has been inserted. In some other versions, the optical fiber 315 may be inserted into the chandelier port 314 at this stage. In either case, a microscope may optionally be utilized to visually inspect the eye to confirm proper positioning of the eye chandelier port 314 relative to the target site. While FIG. 7A shows a particular positioning of the eye chandelier port 314, the eye chandelier port 314 may have any other suitable positioning, as will be apparent to those skilled in the art in view of the teachings herein.

[0068] Once the eye chandelier port (314) is in place, the sclera (304) may be accessed by dissecting the conjunctival flap and retracting the flap. After such dissection is complete, the exposed surface of the sclera (304) may optionally be blanched using a cautery instrument to minimize bleeding. Once the conjunctival abrasion is complete, the exposed surface of the sclera (304) may optionally be dried using a WECK-CEL or other suitable absorbent device.

[0069] A template may then be used to mark the eye (20), as described in U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference, and / or U.S. Pat. No. 11,000,410, issued May 11, 2021, entitled "Guide Device for Tangential Approach to the Suprachoroidal Space," the disclosure of which is incorporated herein by reference in its entirety. The surgeon may then use a visual guide created using the template to attach the suture loop assembly (332) and perform the sclerotomy using a conventional scalpel (313) or other suitable cutting instrument, as shown in FIG. 7B. By way of example only, the suture loop assembly (332) may be formed according to at least some of the teachings of U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. Alternatively, in place of the suture loop assembly (332), the surgeon may place a guide tack in accordance with at least some of the teachings of US Pat. No. 11,000,410, the disclosure of which is incorporated herein by reference in its entirety.

[0070] A sclerotomy procedure involves making a small incision through the sclera (304) of the eye (301). The sclerotomy is performed with particular care to avoid penetrating the choroid (306). Thus, the sclerotomy procedure provides access to the space between the sclera (304) and the choroid (306). Once the incision has been made in the eye (301), blunt dissection may optionally be performed to locally separate the sclera (304) from the choroid (306). Such dissection may be performed using small, blunt, elongated instruments, as would be apparent to one of ordinary skill in the art in view of the teachings herein.

[0071] Once the sclerotomy procedure is performed, the surgeon may insert the cannula (130) of the instrument (100) through the incision and into the space between the sclera (304) and the choroid (306). As seen in FIG. 7C , the cannula (130) is guided into the incision through a suture loop assembly (332). The suture loop assembly (332) may stabilize the cannula (130) during insertion. Additionally, the suture loop assembly (332) maintains the cannula (130) in a generally tangential orientation relative to the incision. Such a tangential orientation may reduce trauma as the cannula (130) is guided through the incision. Once the cannula (130) is inserted into the incision through the suture loop assembly (332), the surgeon may use forceps or other instruments to further guide the cannula (130) along an atraumatic path. Of course, the use of forceps or other instruments is optional and may be omitted in some instances. As previously mentioned, a guide tack (or other device) may be used in place of the suture loop assembly (332). The cannula (130) is advanced until the distal end (132) is positioned near the target area of ​​the subretinal space opposite the choroid (306). Various suitable methods for visualizing the distal end (132), and thereby observing proper positioning of the distal end (132), will be apparent to those skilled in the art in view of the teachings herein.

[0072] Although not shown, in some examples, the cannula 130 may include one or more markers on its surface to indicate various insertion depths. While merely optional, such markers may be desirable to assist the surgeon in identifying the appropriate insertion depth as the cannula 130 is guided along an atraumatic path. For example, the surgeon may visually observe the location of such markers relative to the suture loop assembly 332 and / or relative to the incision in the sclera 304 as an indication of the depth to which the cannula 130 is inserted into the eye 301. By way of example only, one such marker may correspond to approximately 6 mm of insertion depth of the cannula 130.

[0073] As shown in FIG. 7D , once the cannula (130) is at least partially inserted into the eye (301), the surgeon may insert the optical fiber (315) into the eye chandelier port (314), if the optical fiber (315) is not already inserted at this stage. With the eye chandelier port (314) in place and assembled with the optical fiber (315), the surgeon may activate the eye chandelier port (314) by directing light through the optical fiber (315) to provide illumination of the eye (301), thereby visualizing the interior of the eye (301). Further adjustments to the positioning of the cannula (130) may optionally be made at this point to ensure proper positioning relative to the region of retinal geographic atrophy (308). In some cases, the surgeon may wish to rotate the eye (301), such as by pulling the suture loop assembly (332), to orient the pupil of the eye (301) toward the surgeon to optimize visualization of the interior of the eye (301) through the pupil.

[0074] 7C-7D show the cannula 130 being guided between the sclera 304 and choroid 306 to position the distal end 132 of the cannula 130 at a therapeutic agent delivery site. In this example, the delivery site corresponds to the approximately posterior region 301 of the eye, adjacent to an area of ​​retinal geographic atrophy 308. Notably, the delivery site in this example is superior to the macula, in the potential space between the neurosensory retina and the retinal pigment epithelium. By way of example only, the surgeon may rely on direct visualization via a microscope guided through the pupil 301 of the eye as the cannula 130 is advanced through the range of motion shown in FIGS. 7C-7D, with illumination provided via the fiber 315 and port 314. The cannula 130 may be at least partially visible through the retina 308 and choroid 306 of the eye 301. Visual tracking can be enhanced in versions that use optical fibers to emit visible light through the distal end of the cannula (130).

[0075] Once the cannula (130) is advanced to the delivery site, as shown in FIG. 7D, the surgeon may advance the needle (150) of the instrument (100) as previously described by actuating the knob (120). As seen in FIG. 7E, the needle (150) is advanced relative to the cannula (130) so that the needle (150) penetrates the choroid (306) without penetrating the retina (308). Immediately prior to penetrating the choroid (306), the needle (150) may appear under direct visualization to "tension" the surface of the choroid (306). In other words, the needle (150) may deform the choroid (306) by pushing upward, giving it the appearance of a tent pole deforming the roof of a tent. Such a visual phenomenon may be used by the surgeon to identify whether the choroid (306) is about to be punctured and the location of the eventual puncture. The particular amount of needle 150 advancement sufficient to initiate "tenting" and subsequent puncture of the choroid 306 can be any suitable amount, as may be determined by many factors, including, but not limited to, general patient anatomy, local patient anatomy, operator preference, and / or other factors. As previously mentioned, an example range of needle 150 advancement can be between about 0.25 mm and about 10 mm, or, more specifically, between about 2 mm and about 6 mm.

[0076] In this embodiment, after the surgeon confirms proper advancement of the needle 150 by visualizing the aforementioned tenting effect, they inject a balanced salt solution (BSS) or other similar solution as the needle 150 advances relative to the cannula 130. Such BSS may form a leading bleb 340 ahead of the needle 150 as it advances through the choroid 306. The leading bleb 340 may be desirable for two reasons. First, as shown in FIG. 7F, the leading bleb 340 may provide the surgeon with an additional visual indicator to indicate when the needle 150 is properly positioned at the delivery site. Second, the leading bleb 340 may provide a barrier between the needle 150 and the retina 308 once the needle 150 penetrates the choroid 306. Such a barrier may push the retinal wall outward, thereby minimizing the risk of retinal perforation as the needle 150 is advanced to the delivery site. In some versions, a foot pedal is activated to push the leading bleb 340 from the needle 150. Alternatively, other suitable features that may be used to push the leading bleb 340 from the needle 150 will be apparent to those skilled in the art in view of the teachings herein.

[0077] Once the surgeon visualizes the leading bleb (340), the surgeon may stop the injection of BSS, leaving behind a pocket of fluid, as seen in FIG. 7F. A therapeutic agent (342) may then be injected by activating the fluid delivery system (80) or some other fluid delivery device, such as those described in the various references cited herein. The delivered therapeutic agent (342) may be any suitable therapeutic agent configured to treat an ocular condition. Some merely illustrative examples of suitable therapeutic agents may include, but are not necessarily limited to, drugs having smaller or larger molecules, therapeutic cell solutions, certain gene therapy solutions, tissue plasminogen activator, and / or any other suitable therapeutic agent, as will be apparent to those skilled in the art in view of the teachings herein. By way of example only, the therapeutic agent (342) may be provided in accordance with at least some of the teachings of U.S. Patent No. 7,413,734, entitled "Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells," issued August 19, 2008, the entire disclosure of which is incorporated herein by reference. In addition to or instead of being used to deliver a therapeutic agent (342), the instrument (100) and its variations may be used to provide drainage and / or perform other procedures.

[0078] In this example, the amount of therapeutic agent (342) ultimately delivered to the delivery site is approximately 50 μL, although any other suitable amount may be delivered. In some versions, a foot pedal is activated to force the agent (342) out of the needle (150). Alternatively, other suitable features that may be used to force the agent (342) out of the needle (150) will be apparent to those skilled in the art in light of the teachings herein. Delivery of the therapeutic agent (342) may be visualized by the expansion of a pocket of fluid, as seen in FIG. 7G. As shown, the therapeutic agent (342) essentially mixes with the fluid of the preceding bleb (340) as the therapeutic agent (342) is injected into the subretinal space.

[0079] Once delivery is complete, the needle (150) may be retracted by rotating the knob (120) in a direction opposite to that used to advance the needle (150), and the cannula (130) may then be withdrawn from the eye (301). Due to the size of the needle (150), the site where the needle (150) penetrates the choroid (306) is self-sealing, so that no further steps need to be taken to seal the delivery site through the choroid (306). The suture loop assembly (332) and chandelier (314) may be removed, and the incision in the sclera (304) may be closed using any suitable conventional technique.

[0080] As mentioned above, the procedures described above may be performed to treat patients with macular degeneration. In some such instances, the therapeutic agent (342) delivered by the needle (150) may include cells derived from the postpartum umbilicus and placenta. As noted above, by way of example only, the therapeutic agent (342) may be provided in accordance with at least some of the teachings of U.S. Patent No. 7,413,734, the disclosure of which is incorporated herein by reference in its entirety. Alternatively, the needle (150) may be used to deliver any other suitable substance in addition to or instead of those described in U.S. Patent No. 7,413,734 and / or elsewhere herein. By way of example only, the therapeutic agent (342) may include various types of drugs, including, but not limited to, small molecules, large molecules, cells, and / or gene therapy. It should also be understood that macular degeneration is merely an illustrative example of a condition that may be treated by the procedures described herein. Other biological conditions that may be addressed using the devices and procedures described herein will be apparent to those skilled in the art.

[0081] The above procedure may be performed using techniques described in U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety; U.S. Pat. No. 9,949,874, issued April 24, 2018, entitled "Therapeutic Agent Delivery Device with Converging Lumen," the disclosure of which is incorporated herein by reference in its entirety; U.S. Pat. No. 9,925,088, issued March 27, 2018, entitled "Subretinal Tangential Needle Catheter Guide and Introducer," the disclosure of which is incorporated herein by reference in its entirety; and U.S. Pat. No. 10,322,028, issued June 18, 2019, entitled "Method and Apparatus for Detecting Interocular Position," the disclosure of which is incorporated herein by reference in its entirety. No. 10,064,752, issued September 4, 2018, entitled "Powered Suprachoroidal Injection of Therapeutic Agents," the entire disclosure of which is incorporated herein by reference; U.S. Pat. No. 10,219,936, issued March 5, 2019, entitled "Therapeutic Agent Delivery Device with Advanceable Cannula and Needle," the entire disclosure of which is incorporated herein by reference; U.S. Pat. No. 10,258,502, issued April 16, 2019, entitled "Therapeutic Agent Delivery Device," the entire disclosure of which is incorporated herein by reference; and / or WO 2022 / 136913, published June 30, 2022, entitled "Ocular Cannula Guide," the entire disclosure of which is incorporated herein by reference.

[0082] III. Examples of Alternative Cannulas for Instruments

[0083] In some instances, it may be desirable to provide the cannula (130) with an atraumatic wedge-shaped distal end to aid in insertion of the cannula (130) into the space between the sclera (304) and the choroid (306), for example, through a sclerotomy. It will be appreciated that such a wedge-shaped distal end may improve the ability of the cannula (130) to effect separation between the sclera (304) and the choroid (306) by blunt dissection, thereby improving the ability of the cannula (130) to be advanced between such layers without trauma to the scleral or choroidal layers.

[0084] Additionally or alternatively, it may be desirable to provide the cannula 130 with a needle guide (also referred to as an insert) disposed within the needle guide lumen of the cannula 130. In this regard, one example of a needle guide is described in U.S. Pat. No. 10,478,553, the disclosure of which is incorporated herein by reference in its entirety. In some cases, it may be desirable for such a needle guide to be constructed of a material having a relatively low hardness, at least as compared to the hardness of, for example, stainless steel. It will be appreciated that such a relatively low hardness may improve the ability of the cannula 130 to conform to the particular anatomy and contours of the eye 301 by lateral bending as the cannula 130 advances toward the posterior region 301 of the eye between the sclera 304 and choroid 306 layers.

[0085] Additionally or alternatively, it may be desirable to provide the cannula 130 with varying stiffness along its length. For example, it may be desirable to provide a distal segment of the cannula 130 near its distal end with a relatively high stiffness, such as to reduce any curvature that might otherwise be imparted to the cannula 130 by the needle 150 as it is retracted into the cannula 130 (e.g., if the needle 150 includes a preformed bend and / or curve), thereby facilitating atraumatic passage of the cannula 130 along the suprachoroidal space while the needle 150 is being retracted therein, and to provide an intermediate segment of the cannula 130 proximal to the distal segment with a relatively low stiffness, for example, to improve the ability of the cannula 130 to conform to the particular anatomy and contours of the eye 301.

[0086] A. First example of an alternative cannula with varying stiffness

[0087] 8-13 illustrate an example of a cannula (430) that can function in this manner and that can be easily incorporated into the instrument (100) in place of the cannula (130). The cannula (430) can be similar to the cannula (130) described above, except as otherwise described below. For example, like the cannula (130), the cannula (430) has sufficient flexibility to conform to the particular structure and contours of a patient's eye, but the cannula (430) has sufficient column strength to allow advancement of the cannula (430) between the sclera and choroid of the eye (301) without buckling. In some versions, the cannula (430) comprises a flexible material having a hardness greater than that of the flexible material of the cannula (130). For example, the cannula (430) may comprise a flexible material having a hardness greater than polyether block amide (PEBA), although any other suitable material or combination of materials may be used.

[0088] The cannula (430) of this example includes a distal end (432) and a distally facing opening (434) near the distal end (432). The opening (434) of this example is adjacent to a U-shaped lateral recess (436) in the cannula (430) and provides an open distal end (438) of a needle guide lumen (439) within the cannula (430). The opening (434) is spaced proximally from the tip of the distal end (432), while the lateral recess (436) extends the length from the opening (434) to the tip of the distal end (432). In some versions, the opening (434) is oriented along a plane perpendicular to the longitudinal axis of the cannula (430). In some other versions, openings 434 are oriented along a plane that is obliquely oriented relative to the longitudinal axis of cannula 430. In either case, the location and configuration of openings 434 in combination with lateral recesses 436 may be viewed as allowing cannula 430 to provide a pathway for the laterally directed exit of needles 550, 650, 750, 850, 950, 1050, 1150 from cannula 430 as needles 550, 650, 750, 850, 950, 1050, 1150 advance distally from cannula 430, as described below.

[0089] The distal end (432) is atraumatic such that the distal end (432) is configured to provide separation between the sclera (304) and choroid (306) layers via blunt dissection, thereby allowing the cannula (430) to be advanced between such layers without trauma to the sclera or choroid. In this regard, the distal end (432) of this example is defined by a longitudinally extending lower surface (433) and an obliquely extending upper surface (435) that tapers distally downward toward the lower surface (433) such that the distal end (432) is generally wedge-shaped. As shown, in this example, a U-shaped lateral recess (436) extends through the upper surface (435) of the distal end (432). It will be understood that the distal end (432) may be wedge-shaped in any other suitable manner. As described above, the wedge shape of the distal end (432) may improve the ability of the cannula (430) to effect separation between the sclera (304) and the choroid (306) via blunt dissection, thereby improving the ability of the cannula (430) to advance between the sclera (304) and choroid (306) layers without trauma to such layers. The wedge shape of the distal end (432) may also help maintain the angular orientation of the distal end (432) of the cannula (430) about the longitudinal axis of the cannula (430) as the cannula (430) advances toward the posterior region of the eye (301) between the sclera (304) and choroid (306) layers. In other words, the wedge shape of the distal end (432) helps maintain the orientation of the lateral recess (436) toward the interior region of the eye (301), thereby promoting the proper trajectory of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301) as the needle (150, 550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (430).

[0090] In the illustrated example, cannula 430 has a cross-sectional area that varies along the length of cannula 430, and as a result, cannula 430 may have a stiffness that similarly varies along the length of cannula 430. As best shown in Figures 8 and 10-11, cannula 430 in this embodiment includes proximal segment 430p, middle segment 430m, and distal segment 430d. In the illustrated example, distal segment 430d is immediately proximal to wedge-shaped distal end 432 of cannula 430 such that the upper and lower surfaces of distal segment 430d are in direct, continuous contact with the upper and lower surfaces 433, 435 of distal end 432, respectively.

[0091] The proximal segment 430p may have a generally rectangular (e.g., oval) cross-sectional profile and a first cross-sectional area, and may be configured to be manipulated by a surgeon to push or pull the intermediate and distal segments 430m, 430d during use. While the proximal segment 430p in this example has a generally rectangular cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may be used.

[0092] As shown in FIG. 12 , the intermediate segment (430m) has a generally diamond-shaped cross-sectional profile and a second cross-sectional area that is smaller than the first cross-sectional area. In this regard, the cannula (430) may taper laterally and / or laterally inward from the proximal segment (430p) to the intermediate segment (430m). While the intermediate segment (430m) in this embodiment has a generally diamond-shaped cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., rectangular, oval, etc.) may be used. It will be understood that the reduced cross-sectional area of ​​the intermediate segment (430m) relative to the proximal segment (430p) may provide the intermediate segment (430m) with a stiffness that is lower than the stiffness of the proximal segment (430p), thereby contributing to the varying stiffness of the cannula (430) along the length of the cannula (430). As previously mentioned, the relatively low stiffness of the intermediate segment 430m may improve the ability of the cannula 430 to conform to the particular anatomy and contours of the eye 301. In some versions, the intermediate segment 430m has a length that is longer than the respective lengths of the proximal and distal segments 430p, 430d. For example, the intermediate segment 430m may have a length that is longer than the combined lengths of the proximal and distal segments 430p, 430d, and may comprise the majority of the overall length of the cannula 430.

[0093] As shown in FIG. 13, distal segment 430d has a generally rectangular (e.g., oval) cross-sectional profile and a third cross-sectional area that is larger than the second cross-sectional area. In this regard, cannula 430 may taper laterally and / or laterally outward from intermediate segment 430m to distal segment 430d. In some versions, the third cross-sectional area may be smaller than the first cross-sectional area. While distal segment 430d in this example has a generally rectangular cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may be used.

[0094] It will be appreciated that the increased cross-sectional area of ​​distal segment 430d relative to intermediate segment 430m may provide distal segment 430d with a stiffness greater than that of intermediate segment 430m, thereby contributing to the varying stiffness of cannula 430 along its length. In some versions, distal segment 430d of cannula 430 may have a cross-sectional area substantially equal to the cross-sectional area of ​​cannula 130. For example, the width of distal segment 430d may range from about 1.28 mm to about 1.92 mm, or more specifically, about 1.6 mm, and / or the height of distal segment 430d may range from about 0.48 mm to about 0.72 mm, or more specifically, about 0.6 mm. As noted above, cannula 430 may also include a flexible material having a stiffness greater than that of the material of cannula 130. Thus, the distal segment (430d) of the cannula (430) may have increased stiffness relative to the stiffness of the cannula (130). For example, the distal segment (430d) may have a stiffness greater than that of the cannula (130) at or near the distal end (132) of the cannula (130). As previously mentioned, the relatively high stiffness of the distal segment (430d) may reduce any curvature that may be imparted to the cannula (430) by a needle, such as the needle (150), retracted into the cannula (430), thereby facilitating atraumatic passage of the cannula (430) along the suprachoroidal space while the needle (150) is being retracted therein.

[0095] In this embodiment, when the cannula (430) is positioned within the suprachoroidal space, the generally rectangular, oval, or otherwise generally flat cross-sectional profile of the distal segment (430d) of the cannula (430) prevents the cannula (430) from rotating about its longitudinal axis.

[0096] In other words, the cross-sectional profile of the distal segment (430d) of the cannula (430) helps maintain the orientation of the lateral recess (436) toward the interior region of the eye (301), thereby promoting the proper trajectory of the needle (550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301) as the needle (550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (430). Thus, the wedge shape of the distal end 432 in combination with the cross-sectional profile of the distal segment 430d may provide a consistent and predictable exit path for the needle 150, 550, 650, 750, 850, 950, 1050, 1150 as the needle 150, 550, 650, 750, 850, 950, 1050, 1150 advances distally relative to the cannula 430. The cross-sectional profiles of the proximal segment 430p and / or the intermediate segment 430m may provide a similar effect.

[0097] In the illustrated example, the needle guide 441 is disposed within the needle guide lumen 439 of the cannula 430. The needle guide 441 may be secured within the needle guide lumen 439 of the cannula 430 by a press or interference fit, by adhesive, by a mechanical locking mechanism, and / or by any other suitable method. In this example, the needle guide 441 is formed from a polyimide material; however, it should be understood that any other suitable biocompatible material may be used, such as any other suitable biocompatible material having a hardness less than that of stainless steel. The needle guide 441 in this example is substantially straight, but may be curved within the cannula 430. The needle guide 441 defines a needle lumen 443 configured to slidably receive a needle, such as any of the needles 150, 550, 650, 750, 850, 950, 1050, or 1150 described herein. As previously mentioned, the relatively low hardness of the needle guide (441) material may improve the ability of the cannula (430) to conform to the particular anatomy and contours of the eye (301).

[0098] B. A second example of another cannula with varying stiffness

[0099] 14-22 illustrate another example of a cannula (530) that can function as described above and that can be easily incorporated into the instrument (100) in place of the cannula (130). The cannula (530) can be similar to the cannula (430) described above, except as otherwise described below. For example, like the cannula (430), the cannula (530) has sufficient flexibility to conform to the particular structure and contours of a patient's eye, but the cannula (530) has sufficient column strength to allow advancement of the cannula (530) between the sclera and choroid of the eye (301) without buckling. In some versions, the cannula (530) comprises a flexible material having a hardness greater than that of the flexible material of the cannula (130). For example, the cannula (530) may comprise a flexible material having a hardness greater than polyether block amide (PEBA), although any other suitable material or combination of materials may be used.

[0100] The cannula (530) of this example includes a distal end (532) and a distally facing opening (534) near the distal end (532). The opening (534) of this example is adjacent to a U-shaped lateral recess (536) in the cannula (530) and provides an open distal end (538) of a needle guide lumen (539) within the cannula (530). The opening (534) is spaced proximally from the tip of the distal end (532) by a first distance (D1), while the lateral recess (536) extends the length from the opening (534) to the tip of the distal end (532). By way of example only, the first distance (D1) may be approximately 1.5 mm. In some versions, the opening (534) is oriented along a plane perpendicular to the longitudinal axis of the cannula (530). In some other versions, opening 534 is oriented along a plane that is obliquely oriented relative to the longitudinal axis of cannula 530. In either case, the location and configuration of opening 534 in combination with lateral recess 536 may be viewed as allowing cannula 530 to provide a pathway for the laterally directed exit of needle 550, 650, 750, 850, 950, 1050, 1150 from cannula 530 as needle 550, 650, 750, 850, 950, 1050, 1150 advances distally from cannula 530, as described below.

[0101] The distal end (532) is atraumatic such that the distal end (532) is configured to effect separation between the sclera (304) and choroid (306) layers via blunt dissection, thereby allowing the cannula (530) to be advanced between such layers without trauma to the sclera or choroid. In this regard, the distal end (532) of this example is defined by a longitudinally extending lower surface (533) and an obliquely extending upper surface (535) that tapers distally downward toward the lower surface (533) such that the distal end (532) is generally wedge-shaped. As shown, in this example, a U-shaped lateral recess (536) extends through the upper surface (535) of the distal end (532). It will be understood that the distal end (532) may be provided with a wedge shape in any other suitable manner. As described above, the wedge shape of the distal end 532 may improve the ability of the cannula 530 to effect separation between the sclera 304 and the choroid 306 via blunt dissection, thereby improving the ability of the cannula 530 to advance between the sclera 304 and choroid 306 layers without trauma to such layers. The wedge shape of the distal end 532 may also help maintain the angular orientation of the distal end 532 of the cannula 530 about the longitudinal axis of the cannula 530 as the cannula 530 advances toward the posterior region of the eye 301 between the sclera 304 and choroid 306 layers. In other words, the wedge shape of the distal end (532) helps maintain the orientation of the lateral recess (536) toward the interior region of the eye (301), thereby promoting the proper trajectory of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301) as the needle (150, 550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (530).

[0102] In the illustrated example, cannula 530 has a cross-sectional area that varies along the length of cannula 530, and as a result, cannula 530 may have a stiffness that similarly varies along the length of cannula 530. As best shown in Figures 14 and 16-18, cannula 530 in this embodiment includes proximal segment 530p, middle segment 530m, and distal segment 530d. In the illustrated example, distal segment 530d is immediately proximal to wedge-shaped distal end 532 of cannula 530 such that the upper and lower surfaces of distal segment 530d are in direct, continuous contact with the upper and lower surfaces 533, 535 of distal end 532, respectively. More specifically, the distal segment (530d) extends between a distal end that is a second distance (D2) proximally spaced from the tip of the distal end (532) and a proximal end that is a third distance (D3) proximally spaced from the tip of the distal end (532), the intermediate segment (530m) extends between a distal end that is the third distance (D3) proximally spaced from the tip of the distal end (532) and a proximal end that is a fourth distance (D4) proximally spaced from the tip of the distal end (532), and the proximal segment (530p) extends proximally from the distal end that is a fifth distance (D5) proximally spaced from the tip of the distal end (532). By way of example only, the second distance (D2) may be approximately 3.7 mm, the third distance (D3) may be approximately 6.2 mm, the fourth distance (D4) may be approximately 69 mm, and / or the fifth distance (D5) may be approximately 76.5 mm.

[0103] 19, the proximal segment 530p may have a generally rectangular (e.g., oval) cross-sectional profile and a first cross-sectional area and may be configured to be manipulated by a surgeon to push or pull the intermediate and distal segments 530m, 530d during use. While the proximal segment 530p in this example has a generally rectangular cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may be used.

[0104] As shown in FIGS. 20-21 , the intermediate segment (530m) has a generally diamond-shaped cross-sectional profile and a second cross-sectional area that is smaller than the first cross-sectional area. In this regard, the cannula (530) may taper laterally and / or laterally inwardly from the proximal segment (530p) to the intermediate segment (530m). While the intermediate segment (530m) in this embodiment has a generally diamond-shaped cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., rectangular, oval, etc.) may be used. It will be understood that the reduced cross-sectional area of ​​the intermediate segment (530m) relative to the proximal segment (530p) may provide the intermediate segment (530m) with a stiffness that is lower than the stiffness of the proximal segment (530p), thereby contributing to the varying stiffness of the cannula (530) along the length of the cannula (530). As previously mentioned, the relatively low stiffness of the intermediate segment 530m may improve the ability of the cannula 530 to conform to the particular anatomy and contours of the eye 301. In some versions, the intermediate segment 530m has a length that is longer than the respective lengths of the proximal and distal segments 530p, 530d. For example, the intermediate segment 530m may have a length that is longer than the combined lengths of the proximal and distal segments 530p, 530d, and may comprise the majority of the overall length of the cannula 530.

[0105] As shown in FIG. 22, distal segment 530d has a generally rectangular (e.g., oval) cross-sectional profile and a third cross-sectional area that is larger than the second cross-sectional area. In this regard, cannula 530 may taper laterally and / or laterally outward from intermediate segment 530m to distal segment 530d. In some versions, the third cross-sectional area may be smaller than the first cross-sectional area. While distal segment 530d in this example has a generally rectangular cross-sectional profile, it will be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may be used.

[0106] It will be appreciated that the increased cross-sectional area of ​​distal segment 530d relative to intermediate segment 530m may provide distal segment 530d with a stiffness greater than that of intermediate segment 530m, thereby contributing to the varying stiffness of cannula 530 along its length. In some versions, distal segment 530d of cannula 530 may have a cross-sectional area substantially equal to the cross-sectional area of ​​cannula 130. For example, the width of distal segment 530d may range from about 1.28 mm to about 1.92 mm, or more specifically, about 1.6 mm, and / or the height of distal segment 530d may range from about 0.48 mm to about 0.72 mm, or more specifically, about 0.6 mm. As noted above, cannula 530 may also include a flexible material having a stiffness greater than that of the material of cannula 130. Thus, distal segment 530d of cannula 530 may have an increased stiffness relative to the stiffness of cannula 130. For example, distal segment 530d may have a stiffness greater than the stiffness of cannula 130 at or near distal end 132 of cannula 130. Additionally or alternatively, distal segment 530d and / or distal end 532 may comprise a flexible material having a greater stiffness than proximal segment 530p and / or intermediate segment 530m. For example, distal segment 530d and / or distal end 532 may comprise a first grade of polyether block amide (PEBA) having a first hardness, such as Pebax® 7233SA01MED resin by Arkema of Colombes, France, and proximal segment 530p and / or intermediate segment 530m may comprise a second grade of polyether block amide (PEBA) having a second hardness lower than the first hardness. In this regard, cannula 530 may be manufactured by a two-shot molding process, where distal segment 530d and / or distal end 532 are formed by a first shot in the molding process, and proximal segment 530p and / or intermediate segment 530m are formed by a second shot in the molding process.As previously mentioned, the relatively high stiffness of the distal segment (530d) reduces any curvature that may be imparted to the cannula (530) by a needle, such as the needle (150), being retracted therein, thereby facilitating atraumatic passage of the cannula (530) along the suprachoroidal space while the needle (150) is being retracted therein.

[0107] In this embodiment, when the cannula (530) is positioned within the suprachoroidal space, the generally rectangular, oval, or otherwise generally flat cross-sectional profile of the distal segment (530d) of the cannula (530) prevents the cannula (530) from rotating about its longitudinal axis.

[0108] In other words, the cross-sectional profile of the distal segment (530d) of the cannula (530) helps maintain the orientation of the lateral recess (536) toward the interior region of the eye (301), thereby promoting the proper trajectory of the needle (550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301) as the needle (550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (530). Thus, the wedge shape of the distal end 532 in combination with the cross-sectional profile of the distal segment 530d may provide a consistent and predictable exit path for the needle 150, 550, 650, 750, 850, 950, 1050, 1150 as the needle 150, 550, 650, 750, 850, 950, 1050, 1150 advances distally relative to the cannula 530. The cross-sectional profiles of the proximal segment 530p and / or the intermediate segment 530m may provide a similar effect.

[0109] In the illustrated example, the needle guide 541 is disposed within the needle guide lumen 539 of the cannula 530. The needle guide 541 may be secured within the needle guide lumen 539 of the cannula 530 by a press or interference fit, by adhesive, by a mechanical locking mechanism, and / or by any other suitable method. In some cases, the cannula 530 may be overmolded onto the needle guide 541, such as by the two-shot molding process described above. In this example, the needle guide 541 is formed from a polyimide material; however, it should be understood that any other suitable biocompatible material may be used, such as any other suitable biocompatible material having a hardness less than that of stainless steel. The needle guide 541 in this example is substantially straight, but may be curved within the cannula 530. The needle guide 541 defines a needle lumen 543 configured to slidably receive a needle, such as any of the needles 150, 550, 650, 750, 850, 950, 1050, 1150 described herein. As previously mentioned, the relatively low hardness of the needle guide 541 material may improve the ability of the cannula 530 to conform to the particular anatomy and contours of the eye 301.

[0110] In the illustrated example, the proximal support tube 544 is at least partially disposed within the proximal enlarged portion of the needle guide lumen 539 of the cannula 530, proximal to and coaxial with the needle guide 541. In some versions, the proximal portion of the needle guide 541 may be disposed within the proximal support tube 544 such that the proximal portion of the needle guide 541 may be inserted radially between the needle 150, 550, 650, 750, 850, 950, 1050, 1150 and the support tube 544. The support tube 544 may be secured within the needle guide lumen 539 of the cannula 530 by a press or interference fit, by adhesive, by a mechanical locking mechanism, and / or by any other suitable method. In some cases, the cannula 530 may be overmolded onto the support tube 544, such as by the two-shot molding process described above. In this example, support tube (544) is formed from a polyimide material, although it should be understood that any other suitable biocompatible material may be used, such as any other suitable biocompatible material having a hardness less than that of stainless steel. Thus, support tube (544) may be configured similarly to needle guide (541), but support tube (544) may have a greater wall thickness and / or a greater outer cross-sectional dimension (e.g., diameter) than needle guide (541), thereby providing support tube (544) with a stiffness greater than that of needle guide (541). As shown, support tube (544) extends proximally from cannula (530) a sixth distance (D6). By way of example only, sixth distance (D6) may be approximately 6.5 mm. The relatively high stiffness of the support tube (544) allows the support tube (544) to support the needles (150, 550, 650, 750, 850, 950, 1050, 1150) in regions of the needles (150, 550, 650, 750, 850, 950, 1050, 1150) that are more proximal than the cannula (530), thereby reducing kinking of the needles (150, 550, 650, 750, 850, 950, 1050, 1150) in regions proximal to the cannula (530).It will be appreciated that support tube (544) may directly support needle (150, 550, 650, 750, 850, 950, 1050, 1150), such as when needle guide (541) is not radially interposed between needle (150, 550, 650, 750, 850, 950, 1050, 1150) and support tube (544), or may indirectly support needle (150, 550, 650, 750, 850, 950, 1050, 1150), such as through a proximal portion of needle guide (541) when a proximal portion of needle guide (541) is radially interposed between needle (150, 550, 650, 750, 850, 950, 1050, 1150) and support tube (544).

[0111] In the illustrated example, the cannula 530 may include multiple markers 546 a, 546 b on the surface of the cannula 530 to indicate various insertion depths. The markers 546 a, 546 b may be positioned to assist the surgeon in identifying the appropriate insertion depth as the cannula 530 is guided along an atraumatic path. For example, the surgeon may visually observe the location of the markers 546 a, 546 b relative to the suture loop assembly 332 and / or relative to the incision in the sclera 304 as an indication of the depth to which the cannula 530 is inserted into the eye 301. In the illustrated example, the first marker (546a) is spaced proximally from the tip of the distal end (532) by a seventh distance (D7) so that the first marker (546a) corresponds to an insertion depth of the cannula (530) approximately equal to the seventh distance (D7), and the second marker (546b) is spaced proximally from the tip of the distal end (532) by an eighth distance (D8) so that the second marker (546b) corresponds to an insertion depth of the cannula (530) approximately equal to the eighth distance (D8). Although not shown, the third marker may be spaced proximally from the tip of the distal end (532) by a ninth distance so that the third marker corresponds to an insertion depth of the cannula (530) approximately equal to the ninth distance, and the fourth marker may be spaced proximally from the tip of the distal end (532) by a tenth distance so that the fourth marker corresponds to an insertion depth of the cannula (530) approximately equal to the tenth distance.

[0112] By way of example only, the seventh distance (D7) may range from about 4.5 mm to about 5.5 mm, or more specifically about 5 mm, the eighth distance (D8) may range from about 9.5 mm to about 10.5 mm, or more specifically about 10 mm, the ninth distance may range from about 14.5 mm to about 15.5 mm, or more specifically about 15 mm, and / or the tenth distance may range from about 19.5 mm to about 20.5 mm, or more specifically about 20 mm. It will be appreciated that any suitable number of markers (546a, 546b) may be located on the surface of cannula (530) and may be spaced proximally from the tip of distal end (532) any suitable distance to indicate a corresponding insertion depth.

[0113] IV. Examples of Alternative Needles for Devices

[0114] In some cases, it may be desirable to provide one or more preformed curves on the needle 150 so that the needle 150 can impart at least some curvature to the cannula 130 when the needle 150 is slidably disposed therein. Such curves may improve the ability of the needle 150 to access the subretinal space of relatively small eyes 301 (e.g., approximately 16 mm in diameter, or otherwise less than approximately 24 mm in diameter), at least as compared to the eyes 301 of adult patients (e.g., the eyes of pediatric human patients, or the eyes of non-human patients, such as canine or non-human primate patients). Such curves on the needle 150 may improve the ability of the needle 150 and / or the cannula 130 to conform to the particular anatomy and contours of the eye 301. Additionally or alternatively, such curves may inhibit inadvertent movement of the distal tip 152 of the needle 150 that might otherwise result from movement of the body 110 of the instrument 100. It will be appreciated that by inhibiting such inadvertent movement of the distal tip (152), such a curve may help to consistently maintain the distal tip (152) along a predetermined trajectory and angle it in a predetermined orientation while within the eye (301), thereby improving the ability of the needle (150) to access the subretinal space of the eye (301).

[0115] Various illustrative examples of such needles (550, 650, 750, 850, 950, 1050, 1150) are described in more detail below. Although needles (550, 650, 750, 850, 950, 1050, 1150) are described below in connection with cannula (130), it will be understood that any of needles (550, 650, 750, 850, 950, 1050, 1150) may be used with cannula (430, 530). For example, any of needles (550, 650, 750, 850, 950, 1050, 1150) could be readily incorporated into instrument (100) in place of needle (150), and any of cannulas (430, 530) could be readily incorporated into instrument (100) in place of cannula (130). Although the above examples are provided in the context of a relatively small eye (301), the following teachings may also be used in the context of an eye (301) of an adult patient, and as a result, the following teachings are not limited to the context of a relatively small eye (301).

[0116] A. First example of a needle with a proximal curve and a distal curve

[0117] 23-24 illustrate an example of a needle 550 that can be readily incorporated into the device 100 in place of the needle 150. The needle 550 may be similar to the needle 150 described above, unless otherwise noted below. In this regard, the needle 550 in this example has a sharp distal tip 552 and defines a lumen (not shown). The distal tip 552 in this example has a single bevel configuration. In some other versions, the distal tip 552 has a tribevel configuration or any other suitable configuration, such as those described in U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. Still other suitable forms that the distal tip 552 may take will be apparent to those skilled in the art in light of the teachings herein. In this example, the needle 550 is formed from nitinol, although it should be understood that any other suitable material (e.g., stainless steel, etc.) may be used.

[0118] The needle (550) of this example includes a substantially straight proximal section (560), a substantially curved proximal section (562), a substantially straight intermediate section (564), a substantially curved distal section (566), and a substantially straight distal section (568). The proximal curved section (562) is longitudinally interposed between the proximal straight section (560) and the intermediate straight section (564), the intermediate straight section (564) is longitudinally interposed between the proximal curved section (562) and the distal curved section (566), the distal curved section (566) is longitudinally interposed between the intermediate straight section (564) and the distal straight section (568), and the distal straight section (568) is longitudinally interposed between the distal curved section (566) and the distal tip (552). In the illustrated example, the proximal curved portion 562 and the distal curved portion 566 are curved in opposite directions to give the needle 550 a generally S-shaped configuration. For example, the proximal curved portion 562 is curved distally in a generally clockwise direction within the frame of reference of Figures 23-24, and the distal curved portion 566 is curved distally in a generally counterclockwise direction.

[0119] The proximal straight section 560 may be housed within the body 110 of the instrument 100 to facilitate actuation of the needle 550 via the actuation knob 120, for example, and thus may be configured to remain outside the eye 301 during use. In some other versions, at least a portion of the proximal straight section 560 may be housed within a proximal portion of the cannula 130, 430, 530, but may still be outside the eye 301 during use. The proximal curved section 562 may likewise be configured to remain outside the eye 301 during use, while each of the intermediate straight section 564, distal curved section 566, and distal straight section 568 may be configured to be at least partially disposed within the eye 301 during use. For example, at least the intermediate straight section 564, along with the portion of the cannula 130, 430, 530 within which the intermediate straight section 564 is disposed, may be configured to conform to the curvature of the eye 301. Additionally or alternatively, the proximal curved section 562 may be configured to remain disposed within the cannula 130, 430, 530 when the needle 550 is advanced distally relative to the cannula 130, 430, 530, e.g., during initial tenting and / or subsequent puncture of the choroid 306.

[0120] It should be understood that a portion of the needle 550 may be "disposed within the eye 301 during use" even if a portion of the needle 550 is still within the cannula 130, 430, 530, provided that a corresponding portion of the cannula 130, 430, 530 is disposed within the eye 301. Thus, a portion of the needle 550 need not be exposed distally relative to the cannula 130, 430, 530 for a portion of the needle 550 to be "disposed within the eye 301 during use."

[0121] The needle (550) is configured to provide a proximal curved portion (562) and a distal curved portion (566) as preformed features such that the needle (550) is resiliently biased into the generally S-shaped configuration shown in FIG. 23. In the illustrated example, the proximal straight portion (560) has a length (L1), the proximal curved portion (562) has a constant radius of curvature (R1), an arc length (S1), and a center of curvature (C1) located a distance (X1) from the proximal end of the needle (550) along a first (e.g., horizontal) axis and a distance (Y1) from the proximal end of the needle (550) along a second (e.g., vertical) axis, the intermediate straight portion (564) has a length (L2), the distal curved portion (566) has a constant radius of curvature (R2) and an arc length (S2), and the distal straight portion (568) has a length (L3).

[0122] By way of example only, the length (L1) may range from about 11.52 mm to about 17.28 mm, or more specifically about 14.4 mm, the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically about 18 mm, the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, the distance (X1) may range from about 11.52 mm to about 17.28 mm, or more specifically about 14.4 mm, and the distance (Y1) may range from about 14.36 mm to about 21.54 mm. the length (L2) may be in the range of about 32 mm to about 48 mm, more specifically about 40 mm; the radius of curvature (R2) may be in the range of about 2.8 mm to about 4.2 mm, more specifically about 3.5 mm; the arc length (S2) may be in the range of about 3.36 mm to about 5.04 mm, more specifically about 4.2 mm; and / or the length (L3) may be in the range of about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm.

[0123] The proximal straight section 560 may be configured to extend proximally away from the eye 301 and toward the body 110 of the instrument 100 while the intermediate straight section 564, the distal curved section 566, and / or the distal straight section 568 are disposed within the eye 301. In this regard, the intermediate straight section 564 and the portion of the cannula 130, 430, 530 in which the intermediate straight section 564 is disposed may conform to the curvature of the eye 301, while the proximal curved section 562 may curve in the opposite direction, imparting at least some curvature to the cannula 130, 430, 530 such that the portion of the cannula 130, 430, 530 outside the eye 301 may likewise curve in the opposite direction. For example, in any one or more of the steps shown in Figures 7C-7G, the proximal curve (562) may curve the portion of the cannula (130, 430, 530) outside the eye (301) approximately clockwise in the proximal direction, away from the eye (301) and toward the body (110), within the frame of reference of Figures 7C-7G.

[0124] Such induced bending of the cannula 130, 430, 530 by the proximal curved portion 562 may limit the effect of any movement of the body 110 of the instrument 100 on the position of the distal tip 552, thereby inhibiting inadvertent movement of the distal tip 552 that might otherwise result from movement of the body 110. For example, the proximal curved portion 562 and / or the portion of the cannula 130, 430, 530 in which the proximal curved portion 562 is disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the intermediate straight portion 564, the distal curved portion 566, and the distal straight portion 568 of the needle 550. Additionally or alternatively, the induced curvature of the cannula (130, 430, 530) by the proximal curvature (562) may further assist the portion of the cannula (130, 430, 530) within the eye (301) in conforming to the curvature of the eye (301).

[0125] The needle (550) in this example includes a single proximal curved portion (562) having a constant radius of curvature (R1), although in some other versions, the radius of curvature (R1) may be variable and / or multiple proximal curved portions (562) may be provided, as described in more detail below.

[0126] Distal curved portion (566) may be configured to orient distal tip (552) along one or more predetermined exit axes during distal advancement of needle (550) relative to cannula (130, 430, 530) to protrude from opening (134). For example, distal curved portion (566) may be constructed and operative in accordance with at least a portion of the teachings of U.S. Pat. No. 10,478,553, the disclosure of which is incorporated herein by reference in its entirety.

[0127] B. Second Example of a Needle with a Proximal Curve and a Distal Curve

[0128] 25-26 show another example of a needle 650 that may be readily incorporated into the device 100 in place of the needle 150. The needle 650 may be similar to the needle 550 described above, unless otherwise noted below. In this regard, the needle 650 in this example has a sharpened distal tip 652 and defines a lumen (not shown).

[0129] The needle 650 of this example includes a substantially straight proximal section 660, a substantially curved proximal section 662, a substantially straight intermediate section 664, a substantially curved distal section 666, and a substantially straight distal section 668. In the illustrated example, the proximal curved section 662 and the distal curved section 666 are curved in opposite directions to provide the needle 650 with a generally S-shaped configuration. For example, the proximal curved section 662 is curved distally in a generally clockwise direction within the frame of reference of Figures 25-26, and the distal curved section 666 is curved distally in a generally counterclockwise direction.

[0130] Needle 650 is configured to provide proximal curved portion 662 and distal curved portion 666 as preformed features such that needle 650 is resiliently biased into the generally S-shaped configuration shown in Figure 25. In the illustrated example, proximal straight portion 660 has a length (L1), proximal curved portion 662 has a constant radius of curvature (R1) and arc length (S1), intermediate straight portion 664 has a length (L2), distal curved portion 666 has a constant radius of curvature (R2) and arc length (S2), and distal straight portion 668 has a length (L3).

[0131] By way of example only, the length (L1) may range from about 11.52 mm to about 17.28 mm, or more specifically about 14.4 mm; the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm; the arc length (S1) may range from about 24 mm to about 36 mm, or more specifically about 30 mm; the length (L2) may range from about 24 mm to about 36 mm, or more specifically about 30 mm; the radius of curvature (R2) may range from about 2.8 mm to about 4.2 mm, or more specifically about 3.5 mm; the arc length (S2) may range from about 3.36 mm to about 5.04 mm, or more specifically about 4.2 mm; and / or the length (L3) may range from about 0.56 mm to about 0.84 mm, or more specifically about 0.7 mm.

[0132] In some versions, the proximal curve (662) may curve the portion of the cannula (130, 430, 530) outside the eye (301) away from the eye (301) and toward the body (110) in a manner similar to that described above in connection with Figure 23. Such induced curvature of the cannula (130, 430, 530) by the proximal curve (662) may limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (652), thereby inhibiting inadvertent movement of the distal tip (652) that might otherwise result from movement of the body (110). For example, the proximal curved portion 662 and / or the portion of the cannula 130, 430, 530 in which the proximal curved portion 662 is disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the intermediate straight portion 664, the distal curved portion 666, and the distal straight portion 668 of the needle 650. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by the proximal curved portion 662 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0133] C. A third example of a needle with a proximal curve and a distal curve

[0134] 27-28 show another example of a needle 750 that may be readily incorporated into the device 100 in place of the needle 150. The needle 750 may be similar to the needle 550 described above, unless otherwise noted below. In this regard, the needle 750 in this example has a sharpened distal tip 752 and defines a lumen (not shown).

[0135] The needle 750 of this example includes a substantially straight proximal section 760, a substantially curved proximal section 762, a substantially straight intermediate section 764, a substantially curved distal section 766, and a substantially straight distal section 768. In the illustrated example, the proximal curved section 762 and the distal curved section 766 are curved in opposite directions to provide the needle 750 with a generally S-shaped configuration. For example, the proximal curved section 762 is curved distally in a generally clockwise direction within the frame of reference of Figures 27-28, and the distal curved section 766 is curved distally in a generally counterclockwise direction.

[0136] Needle 750 is configured to provide proximal curved section 762 and distal curved section 766 as preformed features such that needle 750 is resiliently biased into the generally S-shaped configuration shown in Figure 27. In the illustrated example, proximal straight section 760 has a length (L1), proximal curved section 762 has a constant radius of curvature (R1) and arc length (S1), intermediate straight section 764 has a length (L2), distal curved section 766 has a constant radius of curvature (R2) and arc length (S2), and distal straight section 768 has a length (L3).

[0137] By way of example only, the length (L1) may range from about 11.52 mm to about 17.28 mm, or more specifically about 14.4 mm; the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm; the length (L2) may range from about 32 mm to about 48 mm, or more specifically about 40 mm; the radius of curvature (R2) may range from about 2.8 mm to about 4.2 mm, or more specifically about 3.5 mm; the arc length (S2) may range from about 3.36 mm to about 5.04 mm, or more specifically about 4.2 mm; and / or the length (L3) may range from about 0.56 mm to about 0.84 mm, or more specifically about 0.7 mm.

[0138] As another example, the length (L1) may be in the range of about 20 mm to about 30 mm, more specifically about 25 mm; the radius of curvature (R1) may be in the range of about 16 mm to about 24 mm, more specifically about 20 mm; the arc length (S1) may be in the range of about 16 mm to about 24 mm, more specifically about 20 mm; the length (L2) may be in the range of about 36.64 mm to about 54.96 mm, more specifically about 45.8 mm; the radius of curvature (R2) may be in the range of about 2 mm to about 3 mm, more specifically about 2.5 mm; the arc length (S2) may be in the range of about 2.8 mm to about 4.2 mm, more specifically about 3.5 mm; and / or the length (L3) may be in the range of about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm. In some such instances, needle (750) may have an overall length of about 95 mm.

[0139] In some versions, the proximal curve (762) may cause the portion of the cannula (130, 430, 530) outside the eye (301) to curve away from the eye (301) and toward the body (110), in a manner similar to that described above in connection with Figure 23. Such induced curvature of the cannula (130, 430, 530) by the proximal curve (762) may limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (752), thereby inhibiting inadvertent movement of the distal tip (752) that might otherwise result from movement of the body (110). For example, the proximal curved portion 762 and / or the portion of the cannula 130, 430, 530 in which the proximal curved portion 762 is disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the intermediate straight portion 764, the distal curved portion 766, and the distal straight portion 768 of the needle 750. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by the proximal curved portion 762 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0140] D. Example of a needle with a first proximal curve and a second proximal curve and a distal curve

[0141] 29-32 illustrate another example of a needle 850 that may be readily incorporated into the device 100 in place of the needle 150. The needle 850 may be similar to the needle 550 described above, unless otherwise noted below. In this regard, the needle 850 in this example has a sharpened distal tip 852 and defines a lumen (not shown).

[0142] The needle (850) in this example includes a substantially straight proximal portion (860), a first substantially curved proximal portion (862), a second substantially curved proximal portion (863), a substantially straight intermediate portion (864), a substantially curved distal portion (866), and a substantially straight distal portion (868). The first proximal curved portion (862) is longitudinally interposed between the proximal straight portion (860) and the second proximal curved portion (863), the second proximal curved portion (863) is longitudinally interposed between the first proximal curved portion (862) and the intermediate straight portion (864), the intermediate straight portion (864) is longitudinally interposed between the second proximal curved portion (863) and the distal curved portion (866), the distal curved portion (866) is longitudinally interposed between the intermediate straight portion (864) and the distal straight portion (868), and the distal straight portion (868) is longitudinally interposed between the distal curved portion (866) and the distal tip (852). In the illustrated example, the proximal curved portions 862, 863 and the distal curved portion 866 are curved in opposite directions to provide a generally S-shaped configuration for the needle 850. For example, each of the proximal curved portions 862, 863 is curved distally in a generally clockwise direction within the frame of reference of Figures 29-32, and the distal curved portion 866 is curved distally in a generally counterclockwise direction.

[0143] The needle 850 is configured to provide proximal curved portions 862, 863 and distal curved portion 866 as preformed features such that the needle 850 is resiliently biased to assume the generally S-shaped configuration shown in Figures 29 and 31-32. In the illustrated example, the proximal straight portion 860 has a length (L1), the first proximal curved portion 862 has a constant radius of curvature (R1), an arc length (S1), and a center of curvature (C1) defined by a reference circle having a center (C1) and a first diameter (D1) located along a first (e.g., horizontal) axis a distance (X1) from the proximal end of the needle 850 and a second (e.g., vertical) axis a distance (Y1) from the proximal end of the needle 850, and a second proximal curved portion 863 has a constant radius of curvature (R2 ), an arc length (S2), and a center of curvature (C2) defined by a reference circle having a center (C2) and a second diameter (D2) located along a first (e.g., horizontal) axis a distance (X2) from the proximal end of needle (850) and a second (e.g., vertical) axis a distance (Y2) from the proximal end of needle (850), wherein intermediate straight portion (864) has a length (L2), distal curved portion (866) has a constant radius of curvature (R3) and an arc length (S3), and distal straight portion (868) has a length (L3).

[0144] By way of example only, the length (L1) may range from about 11.52 mm to about 17.28 mm, or more specifically about 14.4 mm, the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically about 18 mm, the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, and the distance (X1) may range from about 11.52 mm to about 17.28 mm. The distance (Y1) may be in the range of about 14.4 mm to about 21.6 mm, more specifically about 18 mm, the diameter (D1) may be in the range of about 28.8 mm to about 43.2 mm, more specifically about 36 mm, the radius of curvature (R2) may be in the range of about 10 mm to about 15 mm, more specifically about 12.5 mm, and the arc length (S2) may be in the range of about 16 mm to about 24 mm. The distance (X2) may be in the range of about 15.46 mm to about 23.2 mm, more specifically about 19.33 mm, the distance (Y1) may be in the range of about 12.45 mm to about 18.67 mm, more specifically about 15.56 mm, the diameter (D2) may be in the range of about 20 mm to about 30 mm, more specifically about 25 mm, and the length (L2) may be in the range of about 16 mm to about 20 mm. The radius of curvature (R3) may range from about 2.8 mm to about 4.2 mm, more specifically about 3.5 mm, the arc length (S3) may range from about 3.36 mm to about 5.04 mm, more specifically about 4.2 mm, and / or the length (L3) may range from about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm.

[0145] In some versions, one or both proximal curves (862, 863) may cause the portion of the cannula (130, 430, 530) outside the eye (301) to curve away from the eye (301) and toward the body (110), in a manner similar to that described above in connection with FIG. 23. Such induced curvature of the cannula (130, 430, 530) by one or both proximal curves (862, 863) may limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (852), thereby inhibiting inadvertent movement of the distal tip (852) that might otherwise result from movement of the body (110). For example, one or both proximal curved portions 862, 863 and / or the portion of the cannula 130, 430, 530 in which one or both proximal curved portions 862, 863 are disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the intermediate straight portion 864, the distal curved portion 866, and the distal straight portion 868 of the needle 850. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by one or both proximal curved portions 862, 863 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0146] E. Example of a needle with first and second distal curves

[0147] 33-35 illustrate another example of a needle 950 that can be readily incorporated into the device 100 in place of the needle 150. The needle 950 may be similar to the needle 150 described above, unless otherwise noted below. In this regard, the needle 950 in this example has a sharpened distal tip 952 and defines a lumen (not shown). The distal tip 952 in this example has a single bevel configuration. In some other versions, the distal tip 952 has a tribevel configuration or any other suitable configuration, such as those described in U.S. Pat. No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. Still other suitable forms that the distal tip 952 may take will be apparent to those skilled in the art in light of the teachings herein. In this example, the needle 950 is formed from nitinol, although it should be understood that any other suitable material (e.g., stainless steel, etc.) may be used.

[0148] The needle (950) of this example includes a substantially straight proximal portion (960), a first substantially curved distal portion (965), a second substantially curved distal portion (966), and a substantially straight distal portion (968). The first distal curved portion (965) is longitudinally interposed between the proximal straight portion (960) and the second distal curved portion (966), the second distal curved portion (966) is longitudinally interposed between the first distal curved portion (965) and the distal straight portion (968), and the distal straight portion (968) is longitudinally interposed between the second distal curved portion (966) and the distal tip (952). In the illustrated example, the distal curved portions (965, 966) are curved in the same direction as each other, providing the needle (950) with a generally J-shaped configuration. For example, each of the distal curved portions (965, 966) curves generally counterclockwise in the distal direction within the frame of reference of Figures 33-35.

[0149] Each of the proximal straight portion (960), the distal curved portions (965, 966), and the distal straight portion (968) may be configured to reside at least partially within the eye (301) during use. For example, at least the proximal straight portion (960), along with the portion of the cannula (130, 430, 530) in which the proximal straight portion (960) is disposed, may be configured to conform to the curvature of the eye (301). Additionally or alternatively, the first distal curved portion (965) may have a radius of curvature substantially equal to the radius of curvature of the eye (301).

[0150] Needle (950) is configured to provide distal curves (965, 966) as preformed features such that needle (950) is resiliently biased into the generally J-shaped configuration shown in Figures 33 and 35. In the illustrated example, the proximal straight portion (960) has a length (L1), the first distal curved portion (965) has a constant radius of curvature (R1), an arc length (S1), and a center of curvature (C1) defined by a reference circle having a center (C1) and a diameter (D1) located along a first (e.g., horizontal) axis a distance (X1) from the proximal end of the needle (950) and a distance (Y1) from the proximal end of the needle (950) along a second (e.g., vertical) axis, the second distal curved portion (966) has a constant radius of curvature (R2) and an arc length (S2), and the distal straight portion (968) has a length (L2).

[0151] By way of example only, the length (L1) may range from about 43.52 mm to about 65.28 mm, or more specifically about 54.4 mm, the radius of curvature (R1) may range from about 10 mm to about 15 mm, or more specifically about 12.5 mm, the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, the distance (X1) may range from about 43.52 mm to about 65.28 mm, or more specifically about 54.4 mm, and the distance (Y1) may range from about 9.94 mm to about 14.9 mm. mm, more specifically about 12.42 mm; D1 may be in the range of about 20 mm to about 30 mm, more specifically about 25 mm; the radius of curvature (R2) may be in the range of about 2.8 mm to about 4.2 mm, more specifically about 3.5 mm; the arc length (S2) may be in the range of about 3.36 mm to about 5.04 mm, more specifically about 4.2 mm; and / or the length (L2) may be in the range of about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm.

[0152] In some versions, the first distal curve (965) can impart at least some curvature to the cannula (130, 430, 530), such as during any one or more of the steps shown in Figures 7C-7G. Such induced curvature of the cannula (130, 430, 530) by the first distal curve (965) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (952), thereby inhibiting inadvertent movement of the distal tip (952) that might otherwise result from movement of the body (110). For example, the first distal curved portion 965 and / or the portion of the cannula 130, 430, 530 in which the first distal curved portion 965 is disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the second distal curved portion 966 and distal straight portion 968 of the needle 950. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by the first distal curved portion 965 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0153] The second distal curved portion (966) may be configured to orient the distal tip (952) along one or more predetermined exit axes during distal advancement of the needle (950) relative to the cannula (130, 430, 530) to protrude from the opening (134). For example, the distal curved portion (966) may be constructed and operative in accordance with at least a portion of U.S. Patent No. 10,478,553, the disclosure of which is incorporated herein by reference in its entirety.

[0154] F. Example of a needle having a proximal curve and first and second distal curves

[0155] 36-37 show another example of a needle 1050 that may be readily incorporated into device 100 in place of needle 150. Needle 1050 may be similar to needle 550 and / or needle 950 described above, unless otherwise noted below. In this regard, needle 1050 in this example has a sharpened distal tip 1052 and defines a lumen (not shown).

[0156] The needle (1050) in this example includes a substantially straight proximal portion (1060), a substantially curved proximal portion (1062), a substantially straight intermediate portion (1064), a first substantially curved distal portion (1065), a second substantially curved distal portion (1066), and a substantially straight distal portion (1068). The proximal curved portion (1062) is longitudinally interposed between the proximal straight portion (1060) and the intermediate straight portion (1064), the intermediate straight portion (1064) is longitudinally interposed between the proximal curved portion (1062) and the first distal curved portion (1065), the first distal curved portion (1065) is longitudinally interposed between the intermediate straight portion (1064) and the second distal curved portion (1066), the second distal curved portion (1066) is longitudinally interposed between the first distal curved portion (1065) and the distal straight portion (1068), and the distal straight portion (1068) is longitudinally interposed between the second distal curved portion (1066) and the distal tip (1052). In the illustrated example, the proximal curved portion 1062 and the distal curved portions 1065, 1066 are curved in opposite directions to provide a generally S-shaped configuration for the needle 1050. For example, the proximal curved portion 1062 is curved distally in a generally clockwise direction within the frame of reference of Figures 36-37, and the distal curved portions 1065, 1066 are each curved distally in a generally counterclockwise direction.

[0157] The needle 1050 is configured to provide the proximal curved portion 1062 and the distal curved portions 1065, 1066 as preformed features such that the needle 1050 is resiliently biased to assume the generally S-shaped configuration shown in Figure 36. In the illustrated example, the proximal straight portion 1060 has a length (L1), the proximal curved portion 1062 has a constant radius of curvature (R1) and an arc length (S1), the intermediate straight portion 1064 has a length (L2), the first distal curved portion 1065 has a constant radius of curvature (R2) and an arc length (S2), the second distal curved portion 1066 has a constant radius of curvature (R3) and an arc length (S3), and the distal straight portion 1068 has a length (L3).

[0158] By way of example only, the length (L1) may range from about 19.92 mm to about 29.88 mm, or more specifically about 24.9 mm, the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, the length (L2) may range from about 16 mm to about 24 mm, or more specifically about 20 mm, and the radius of curvature (R2) may range from about 13.6 mm to about 20.4 mm. and / or the length (L3) may be in the range of about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm.

[0159] In some versions, the intermediate straight section (1064) may be omitted, allowing the proximal curved section (1062) to join directly with the first distal curved section (1065). Additionally or alternatively, the proximal straight section (1060) may have a slight curvature, such that the proximal straight section (1060) may have an arc length (S0). In some versions, the arc lengths (S0, S1, S2, S3) of the proximal straight section (1060), the proximal curved section (1062), the first distal curved section (1065), and the second distal curved section (1066) may be selected from the table below, with all values ​​being approximate. [Table 1]

[0160] In some versions, the proximal curve (1062) may curve the portion of the cannula (130, 430, 530) outside the eye (301) away from the eye (301) and toward the body (110) in a manner similar to that described above in connection with Figure 23. Such induced curvature of the cannula (130, 430, 530) by the proximal curve (1062) may limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (1052), thereby inhibiting inadvertent movement of the distal tip (1052) that might otherwise result from movement of the body (110). For example, the proximal curved portion 1062 and / or the portion of the cannula 130, 430, 530 in which the proximal curved portion 1062 is disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the intermediate straight portion 1064, the first distal curved portion 1065, the second distal curved portion 1066, and the distal straight portion 1068 of the needle 1050. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by the proximal curved portion 1062 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0161] G. Example of a needle having first and second proximal curves and first and second distal curves

[0162] 38-39 show another example of needle 1150 that may be readily incorporated into device 100 in place of needle 150. Needle 1150 may be similar to needle 550 and / or needle 950 described above, unless otherwise noted below. In this regard, needle 1150 in this example has a sharpened distal tip 1152 and defines a lumen (not shown).

[0163] The needle (1150) in this example includes a substantially straight proximal portion (1160), a first substantially curved proximal portion (1162), a second substantially curved proximal portion (1163), a first substantially curved distal portion (1165), a second substantially curved distal portion (1166), and a substantially straight distal portion (1168). The first proximal curved portion (1162) is longitudinally interposed between the proximal straight portion (1160) and the second proximal curved portion (1163), the second proximal curved portion (1163) is longitudinally interposed between the first proximal curved portion (1162) and the first distal curved portion (1165), the first distal curved portion (1165) is longitudinally interposed between the second proximal curved portion (1163) and the second distal curved portion (1166), the second distal curved portion (1166) is longitudinally interposed between the first distal curved portion (1165) and the distal straight portion (1168), and the distal straight portion (1168) is longitudinally interposed between the second distal curved portion (1166) and the distal tip (1152). In some versions, the needle 1150 can include, for example, a substantially straight intermediate portion (not shown) longitudinally interposed between the second proximal curved portion 1163 and the first distal curved portion 1165. In the illustrated example, the proximal curved portions 1162, 1163 and the distal curved portions 1165, 1166 are curved in opposite directions to provide the needle 1150 with a generally S-shaped configuration. For example, each of the proximal curved portions 1162, 1163 is curved distally in a generally clockwise direction within the frame of reference of FIGS. 38-39 , and each of the distal curved portions 1165, 1166 is curved distally in a generally counterclockwise direction.

[0164] The needle (1150) is configured to provide proximal curved portions (1162, 1163) and distal curved portions (1165, 1166) as preformed features such that the needle (1150) is resiliently biased to assume the generally S-shaped configuration shown in FIG. 38. In the illustrated example, the proximal straight portion (1160) has a length (L1), the first proximal curved portion (1162) has a constant radius of curvature (R1) and an arc length (S1), the second proximal curved portion (1163) has a constant radius of curvature (R2) and an arc length (S2), the first distal curved portion (1165) has a constant radius of curvature (R3) and an arc length (S3), the second distal curved portion (1166) has a constant radius of curvature (R4) and an arc length (S4), and the distal straight portion (1168) has a length (L2).

[0165] By way of example only, the length (L1) may range from about 12.08 mm to about 18.12 mm, or more specifically about 15.1 mm; the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically about 18 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically about 20 mm; the radius of curvature (R2) may range from about 10 mm to about 15 mm, or more specifically about 12.5 mm; and the arc length (S2) may range from about 16 mm to about 24 mm, or more specifically about 20 mm. For example, the radius of curvature (R3) may be in the range of about 10 mm to about 15 mm, more specifically about 12.5 mm, the arc length (S3) may be in the range of about 16 mm to about 24 mm, more specifically about 20 mm, the radius of curvature (R4) may be in the range of about 2.8 mm to about 4.2 mm, more specifically about 3.5 mm, the arc length (S4) may be in the range of about 3.36 mm to about 5.04 mm, more specifically about 4.2 mm, and / or the length (L2) may be in the range of about 0.56 mm to about 0.84 mm, more specifically about 0.7 mm.

[0166] In some versions, one or both proximal curves 1162, 1163 may cause the portion of the cannula 130, 430, 530 outside the eye 301 to curve away from the eye 301 and toward the body 110, in a manner similar to that described above in connection with FIGURE 23. Such induced curvature of the cannula 130, 430, 530 by one or both proximal curves 1162, 1163 may limit the effect of any movement of the body 110 of the instrument 100 on the position of the distal tip 1152, thereby inhibiting inadvertent movement of the distal tip 1152 that might otherwise result from movement of the body 110. For example, one or both proximal curved portions 1162, 1163 and / or the portion of the cannula 130, 430, 530 in which one or both proximal curved portions 1162, 1163 are disposed may effectively absorb some or all of such movement instead of transmitting such movement distally to the first distal curved portion 1165, the second distal curved portion 1166, and the distal straight portion 1168 of the needle 1150. Additionally or alternatively, the induced curvature of the cannula 130, 430, 530 by one or both proximal curved portions 1162, 1163 may further assist the portion of the cannula 130, 430, 530 within the eye 301 in conforming to the curvature of the eye 301.

[0167] V. Typical combinations

[0168] The following examples illustrate various, non-exhaustive ways in which the teachings herein may be combined or applied. It should be understood that the following examples are not intended to limit the scope of any claims that may be presented at any time in this application or any subsequent application of this application. No disclaimer is intended. The following examples are provided for illustrative purposes only. It is contemplated that the various teachings herein may be arranged and applied in many other ways. It is also contemplated that some variations may omit certain features referred to in the following examples. Accordingly, none of the aspects or features referred to below should be considered critical unless expressly indicated as such at a later date by the inventor or the inventor's successor in interest. If a claim is presented in this application or any subsequent application related to this application that includes additional features other than those referred to below, those additional features shall not be presumed to have been added for any reasons related to patentability.

[0169] Example 1

[0170] (b) a cannula extending distally from the body, the cannula being flexible and dimensioned and configured for advancement between the sclera and choroid of a patient's eye; and (c) a needle slidably disposed within the cannula, the needle having (i) a sharp distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to be located inside the cannula when the needle is in the proximal position and the distal tip configured to be located outside the cannula when the needle is in the distal position. and a needle including: (ii) at least one proximal curve, wherein the needle is resiliently biased to extend along the at least one proximal curve through the at least one proximal curve; and (iii) at least one distal curve, wherein the needle is resiliently biased to extend along the at least one distal curve through the at least one distal curve, the at least one distal curve being different from the at least one proximal curve.

[0171] Example 2

[0172] The device of Example 1, wherein the needle further includes a distal straight portion extending along the exit axis, the distal straight portion being longitudinally interposed between the at least one distal curved portion and the sharp distal tip, and the needle is resiliently biased to extend along a linear path along the distal straight portion.

[0173] Example 3

[0174] 3. The device of claim 1 or 2, wherein the needle further comprises a proximal straight portion, at least one proximal curved portion longitudinally interposed between the proximal straight portion and the at least one distal curved portion, and the needle is resiliently biased to extend along a linear path along the proximal straight portion.

[0175] Example 4

[0176] 4. The device of any one of Examples 1 to 3, wherein the needle further comprises an intermediate straight portion, the intermediate straight portion being longitudinally interposed between the at least one proximal curved portion and the at least one distal curved portion, and the needle is resiliently biased to extend along a linear path along the intermediate straight portion.

[0177] Example 5

[0178] 5. The device of any one of Examples 1 to 4, wherein the at least one proximal curved portion includes first and second proximal curved portions, and the needle is resiliently biased to extend through and along the first and second proximal curved portions, respectively.

[0179] Example 6

[0180] 6. The device of any one of Examples 1 to 5, wherein the at least one distal curved portion includes first and second distal curved portions, and the needle is resiliently biased to extend through the first and second distal curved portions and along the first and second distal curves, respectively.

[0181] Example 7

[0182] 7. The device of any one of Examples 1 to 6, wherein at least one proximal curved portion and at least one distal curved portion are curved in opposite directions to each other.

[0183] Example 8

[0184] 8. The device of any one of Examples 1 to 7, wherein the needle is resiliently biased to define an "S" shape.

[0185] Example 9

[0186] 9. The device of any one of Examples 1 to 8, wherein the at least one proximal curved portion is configured to reside within the cannula when the needle is in the distal position.

[0187] Example 10

[0188] 10. The device of any one of Examples 1 to 9, wherein the at least one proximal curve is configured to be located outside the patient's eye when the needle is in the distal position.

[0189] Example 11

[0190] 11. The device of any one of Examples 1 to 10, wherein at least one proximal curved portion is configured to inhibit movement of the body from being transmitted to the distal tip.

[0191] Example 12

[0192] 12. The device of any one of Examples 1 to 11, wherein the at least one proximal curved portion is configured to impart a curvature to the cannula.

[0193] Example 13

[0194] 13. The device of any one of Examples 1 to 12, wherein the needle comprises nitinol.

[0195] Example 14

[0196] 14. The device of any one of Examples 1 to 13, wherein the distal tip is beveled.

[0197] Example 15

[0198] 15. The device of any one of Examples 1 to 14, wherein the cannula is sufficiently flexible to conform to the anatomy and contours of the patient's eye, yet the cannula has sufficient column strength to allow advancement of the cannula between the sclera and choroid of the patient's eye without buckling.

[0199] Example 16

[0200] 16. The device of any one of Examples 1 to 15, further comprising: (a) a needle guide positioned between the needle and the cannula; and (b) a support tube positioned partially within the cannula proximal to the needle guide, the support tube extending proximally from the cannula, wherein the support tube is more rigid than the needle guide.

[0201] Example 17

[0202] 17. The device of example 16, wherein the support tube and the needle guide comprise the same material as each other.

[0203] Example 18

[0204] 18. The device of any one of Examples 1 to 17, wherein the cannula comprises a proximal segment comprising a first material and a distal segment comprising a second material different from the first material.

[0205] Example 19

[0206] 19. The device of any one of Examples 1 to 18, wherein at least one proximal curved portion has an arc length in the range of about 16 mm to about 24 mm.

[0207] Example 20

[0208] 20. The device of any one of Examples 1 to 19, wherein at least one proximal curve has a radius of curvature ranging from about 16 mm to about 24 mm.

[0209] Example 21

[0210] 21. The device of any one of Examples 1 to 20, wherein at least one distal curved portion has an arc length in the range of about 2.8 mm to about 4.2 mm.

[0211] Example 22

[0212] 22. The device of any one of Examples 1 to 21, wherein at least one distal curve has a radius of curvature in the range of about 2 mm to about 3 mm.

[0213] Example 23

[0214] 23. The device of any one of Examples 2 to 22, wherein the distal straight portion has a length in the range of about 0.56 mm to about 0.84 mm.

[0215] Example 24

[0216] 24. The device of any one of Examples 3 to 23, wherein the proximal straight portion has a length in the range of about 20 mm to about 30 mm.

[0217] Example 25

[0218] 25. The device of any one of Examples 4 to 24, wherein the intermediate straight section has a length in the range of about 36.64 mm to about 54.96 mm.

[0219] Example 26

[0220] (b) a cannula extending distally from the body, the cannula being flexible and dimensioned and configured for advancement between the sclera and choroid of a patient's eye; and (c) a needle slidably disposed within the cannula, the needle having (i) a sharp distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to reside inside the cannula when the needle is in the proximal position. a needle including: (i) a sharp distal tip formed on a cannula such that the distal tip is located outside the cannula when the needle is in a distal position; (ii) a first curved portion, the first curved portion being resiliently biased to cause the needle to extend through the first curved portion along a first curve; and (iii) a second curved portion longitudinally spaced from the first curved portion, the second curved portion being resiliently biased to cause the needle to extend through the second curved portion along a second curve.

[0221] Example 27

[0222] 1. A device comprising: (a) a body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being dimensioned and configured for advancement between the sclera and choroid of a patient's eye, the cannula including: (i) a proximal segment having a first cross-sectional area; (ii) an intermediate segment having a second cross-sectional area; and (iii) a distal segment having a third cross-sectional area greater than the second cross-sectional area; and (c) a needle slidably disposed within the cannula.

[0223] Example 28

[0224] 28. The apparatus of example 27, wherein the second cross-sectional area is smaller than the first cross-sectional area.

[0225] Example 29

[0226] The device of Example 27 or 28, wherein the proximal segment has a first cross-sectional shape, the intermediate segment has a second cross-sectional shape, and the distal segment has a third cross-sectional shape different from the second cross-sectional shape.

[0227] Example 30

[0228] 30. The device of any one of Examples 27 to 29, wherein the cannula further comprises a wedge-shaped distal end.

[0229] Example 31

[0230] 31. A device described in any one of Examples 27 to 30, wherein the proximal segment has a first stiffness and the intermediate segment has a second stiffness different from the first stiffness.

[0231] Example 32

[0232] 32. The device of example 31, wherein the second stiffness is less than the first stiffness.

[0233] Example 33

[0234] The device of example 31 or 32, wherein the distal segment has a third stiffness different from the second stiffness.

[0235] Example 34

[0236] 1. A device comprising: (a) a body; (b) a cannula extending distally from the body along a length, the cannula being flexible, the cannula being dimensioned and configured for advancement between the sclera and choroid of a patient's eye, the cannula having a stiffness that varies along its length; and (c) a needle slidably disposed within the cannula.

[0237] Example 35

[0238] The device of Example 34, wherein the cannula includes (i) a proximal segment having a first stiffness, (ii) an intermediate segment having a second stiffness different from the first stiffness, and (iii) a distal segment having a third stiffness different from the second stiffness.

[0239] Example 36

[0240] The device of Example 35, wherein the distal segment comprises a first material and at least one of the proximal segment or the intermediate segment comprises a second material different from the first material.

[0241] VI. Other

[0242] While some examples herein are described in the context of a cannula guide positioned near an already-formed sclerotomy 23, it should be understood that other types of procedures may be used. For example, in some variations of the procedures described herein, a cannula guide may be secured to the eye 20 first, and then the sclerotomy 23 may be formed after the cannula guide is secured to the eye 20. Other suitable steps and sequences that may be performed in a procedure involving the combination of a sclerotomy 23 and a cannula guide will be apparent to one of ordinary skill in the art in view of the teachings herein.

[0243] It should be understood that any of the versions of the devices described herein may include various other features in addition to or in place of those described above. By way of example only, any of the devices herein may also include one or more of the various features disclosed in any of the various references incorporated herein by reference.

[0244] It should be understood that any one or more of the teachings, expressions, embodiments, examples, etc. described herein may be combined with any one or more of the other teachings, expressions, embodiments, examples, etc. described herein. Accordingly, the foregoing teachings, expressions, embodiments, examples, etc. should not be viewed in isolation from one another. Various suitable ways in which the teachings herein may be combined will be readily apparent to those skilled in the art in light of the teachings herein. Such modifications and variations are intended to be included within the scope of the following claims.

[0245] Any patent, publication, or other disclosure material that is said to be incorporated by reference herein should be understood to be incorporated herein only to the extent that the incorporated material does not contradict existing definitions, descriptions, or other disclosure material set forth in this disclosure. Thus, to the extent necessary, the disclosure expressly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or portion thereof, that is said to be incorporated herein by reference but that contradicts existing definitions, descriptions, or other disclosure material set forth herein is incorporated only to the extent that no contradiction arises between the incorporated material and the existing disclosure material.

[0246] The above versions may be designed to be disposed of after a single use, or they may be designed to be used multiple times. In either or both cases, versions may be reconditioned for reuse after at least one use. Reconditioning may include any combination of the steps of disassembly of the device, followed by cleaning or replacement of particular parts, and subsequent reassembly. In particular, some versions of the device may be disassembled, and any number of particular parts or portions of the device may be selectively replaced or removed in any combination. Upon cleaning and / or replacement of particular parts, some versions of the device may be reassembled for subsequent use either at a reconditioning facility, or by a surgeon immediately prior to a procedure. Those skilled in the art will appreciate that reconditioning of a device may utilize a variety of techniques for disassembly, cleaning / replacement, and reassembly. Use of such techniques, and the resulting reconditioned device, are all within the scope of the present application.

[0247] By way of example only, the versions described herein may be sterilized before and / or after treatment. In one sterilization technique, the device is placed in a closed, sealed container, such as a plastic or TYVEK bag. The container and device may then be placed in a field of radiation that can penetrate the container, such as gamma radiation, x-rays, or high-energy electrons. The radiation may kill bacteria on the device and in the container. The sterilized device may then be stored in the sterile container for later use. The device may also be sterilized using any other technique known in the art, including, but not limited to, beta or gamma radiation, ethylene oxide, or steam.

[0248] While various embodiments of the present invention have been shown and described, further adaptations of the methods and systems described herein may be achieved by appropriate modifications by those skilled in the art without departing from the scope of the present invention. Some such potential modifications have been mentioned above, and others will be apparent to those skilled in the art. For example, the foregoing examples, embodiments, geometries, materials, dimensions, proportions, steps, etc., are illustrative and not required. Accordingly, the scope of the present invention should be considered in terms of the following claims, and is understood not to be limited to the details of structure and operation shown and described in the specification and drawings.

[0249] [Embodiment] (1) (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being sized and configured to be advanced between the sclera and the choroid of the patient's eye; (c) a needle slidably disposed within the cannula, (i) a sharpened distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to be located inside the cannula when the needle is in the proximal position and the distal tip configured to be located outside the cannula when the needle is in the distal position; (ii) at least one proximal curved portion, wherein the needle is resiliently biased to extend through the at least one proximal curved portion and along at least one proximal curve; (iii) at least one distal curve, wherein the needle is resiliently biased to extend along at least one distal curve through the at least one distal curve, the at least one distal curve being different from the at least one proximal curve; a needle including An apparatus comprising: (2) The device of embodiment 1, wherein the needle further comprises a distal straight portion extending along the exit axis, the distal straight portion being longitudinally interposed between the at least one distal curved portion and the sharp distal tip, and the needle is resiliently biased to extend along a linear path along the distal straight portion. (3) The device of any one of claims 1 to 2, wherein the needle further comprises a proximal straight portion, the at least one proximal curved portion being longitudinally interposed between the proximal straight portion and the at least one distal curved portion, and the needle is resiliently biased to extend along a linear path along the proximal straight portion. (4) The device of any one of claims 1 to 3, wherein the needle further comprises an intermediate straight portion, the intermediate straight portion being longitudinally interposed between the at least one proximal curved portion and the at least one distal curved portion, and the needle is resiliently biased to extend along a linear path along the intermediate straight portion. (5) The device of any one of claims 1 to 4, wherein the at least one proximal curved portion includes first and second proximal curved portions, and the needle is resiliently biased to extend through the first and second proximal curved portions along the first and second proximal curved portions, respectively.

[0250] (6) The device of any one of claims 1 to 5, wherein the at least one distal curved portion includes first and second distal curved portions, and the needle is resiliently biased to extend through the first and second distal curved portions and along the first and second distal curved portions, respectively. (7) The device described in any one of embodiments 1 to 6, wherein the at least one proximal curved portion and the at least one distal curved portion are curved in opposite directions to each other. (8) A device as described in any one of claims 1 to 7, wherein the needle is resiliently biased to define an "S" shape. (9) The device of any one of embodiments 1 to 8, wherein the at least one proximal curved portion is configured to be located within the cannula when the needle is in the distal position. (10) The device of any one of embodiments 1 to 9, wherein the at least one proximal curved portion is configured to be located outside the patient's eye when the needle is in the distal position.

[0251] (11) The device described in any one of embodiments 1 to 10, wherein the at least one proximal curved portion is configured to prevent movement of the body from being transmitted to the distal tip. (12) The device described in any one of embodiments 1 to 11, wherein the at least one proximal curved portion is configured to impart a curvature to the cannula. (13) The device of any one of claims 1 to 12, wherein the needle comprises nitinol. (14) The device of any one of embodiments 1 to 13, wherein the distal tip is beveled. (15) The device of any one of claims 1 to 14, wherein the cannula is sufficiently flexible to conform to the anatomy and contours of the patient's eye, yet the cannula has sufficient column strength to permit advancement of the cannula between the sclera and the choroid of the patient's eye without buckling.

[0252] (16) (a) a needle guide disposed between the needle and the cannula; (b) a support tube disposed partially within the cannula proximal to the needle guide, the support tube extending proximally from the cannula; Further provided with the support tube being more rigid than the needle guide; An apparatus described in any one of embodiments 1 to 15. (17) The device of embodiment 16, wherein the support tube and the needle guide comprise the same material. (18) The device of any one of embodiments 1 to 17, wherein the cannula includes a proximal segment including a first material and a distal segment including a second material different from the first material. (19) The device of any one of embodiments 1 to 18, wherein the at least one proximal curved portion has an arc length ranging from about 16 mm to about 24 mm. (20) The device described in any one of embodiments 1 to 19, wherein the at least one proximal curve has a radius of curvature ranging from about 16 mm to about 24 mm.

[0253] (21) The device of any one of embodiments 1 to 20, wherein the at least one distal curved portion has an arc length in the range of about 2.8 mm to about 4.2 mm. (22) The device described in any one of embodiments 1 to 21, wherein the at least one distal curve has a radius of curvature ranging from about 2 mm to about 3 mm. (23) The device described in any one of embodiments 2 to 22, wherein the distal straight portion has a length in the range of about 0.56 mm to about 0.84 mm. (24) The device described in any one of embodiments 3 to 23, wherein the proximal straight portion has a length in the range of about 20 mm to about 30 mm. (25) The device of any one of embodiments 4 to 24, wherein the intermediate straight section has a length in the range of about 36.64 mm to about 54.96 mm.

[0254] (26) (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being sized and configured to be advanced between the sclera and the choroid of the patient's eye; (c) a needle slidably disposed within the cannula, (i) a sharpened distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to be located inside the cannula when the needle is in the proximal position and the distal tip configured to be located outside the cannula when the needle is in the distal position; (ii) a first curved portion, the needle being resiliently biased to extend through the first curved portion along a first curve; (iii) a second curved portion longitudinally spaced from the first curved portion, the needle being resiliently biased to extend through the second curved portion along a second curve; a needle; An apparatus comprising: (27) (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being sized and configured to be advanced between the sclera and the choroid of the patient's eye, the cannula comprising: (i) a proximal segment having a first cross-sectional area; (ii) an intermediate segment having a second cross-sectional area; (iii) a distal segment having a third cross-sectional area greater than the second cross-sectional area; a cannula including: (c) a needle slidably disposed within the cannula; An apparatus comprising: (28) The device of embodiment 27, wherein the second cross-sectional area is smaller than the first cross-sectional area. (29) The device described in embodiment 27 or 28, wherein the proximal segment has a first cross-sectional shape, the intermediate segment has a second cross-sectional shape, and the distal segment has a third cross-sectional shape different from the second cross-sectional shape. (30) The device of any one of embodiments 27 to 29, wherein the cannula further comprises a wedge-shaped distal end.

[0255] (31) The device described in any one of embodiments 27 to 30, wherein the proximal segment has a first stiffness and the intermediate segment has a second stiffness different from the first stiffness. (32) The device described in embodiment 31, wherein the second stiffness is less than the first stiffness. (33) The device described in embodiment 31 or 32, wherein the distal segment has a third stiffness different from the second stiffness. (34) (a) a main body; (b) a cannula extending distally from the body along a length, the cannula being flexible, the cannula being dimensioned and configured to be advanced between the sclera and choroid of a patient's eye, the cannula having a stiffness that varies along the length; (c) a needle slidably disposed within the cannula; An apparatus comprising: (35) The cannula comprises: (i) a proximal segment having a first stiffness; (ii) an intermediate segment having a second stiffness different from the first stiffness; (iii) a distal segment having a third stiffness different from the second stiffness; and 35. The device of embodiment 34, comprising:

[0256] (36) The device of embodiment 35, wherein the distal segment comprises a first material and at least one of the proximal segment or the intermediate segment comprises a second material different from the first material.

Claims

1. (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being dimensioned and configured to be advanced between the sclera and the choroid of the patient's eye; (c) a needle slidably disposed within the cannula, (i) a sharpened distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to be located inside the cannula when the needle is in the proximal position and the distal tip configured to be located outside the cannula when the needle is in the distal position; (ii) at least one proximal curved portion, wherein the needle is resiliently biased to extend through the at least one proximal curved portion and along at least one proximal curve; (iii) at least one distal curve, wherein the needle is resiliently biased to extend along at least one distal curve through the at least one distal curve, the at least one distal curve being different from the at least one proximal curve; a needle including An apparatus comprising:

2. 10. The device of claim 1, wherein the needle further comprises a distal straight portion extending along an exit axis, the distal straight portion being longitudinally interposed between the at least one distal curved portion and the sharp distal tip, the needle being resiliently biased to extend along a linear path along the distal straight portion.

3. 3. The device of claim 1, wherein the needle further comprises a proximal straight portion, the at least one proximal curved portion being longitudinally interposed between the proximal straight portion and the at least one distal curved portion, and the needle is resiliently biased to extend along a linear path along the proximal straight portion.

4. 10. The device of claim 1, wherein the needle further comprises an intermediate straight portion longitudinally interposed between the at least one proximal curved portion and the at least one distal curved portion, the needle being resiliently biased to extend along a linear path along the intermediate straight portion.

5. 10. The device of claim 1, wherein the at least one proximal curved portion includes first and second proximal curved portions, and the needle is resiliently biased to extend through the first and second proximal curved portions and along first and second proximal curved portions, respectively.

6. 10. The device of claim 1, wherein the at least one distal curved portion includes first and second distal curved portions, and the needle is resiliently biased to extend through the first and second distal curved portions and along first and second distal curved portions, respectively.

7. The device of claim 1 , wherein the at least one proximal curved portion and the at least one distal curved portion are curved in opposite directions.

8. The device of claim 1 , wherein the needle is resiliently biased to define an "S" shape.

9. The device of claim 1 , wherein the at least one proximal curve is configured to reside within the cannula when the needle is in the distal position.

10. The device of claim 1 , wherein the at least one proximal curve is configured to be located outside the patient's eye when the needle is in the distal position.

11. The device of claim 1 , wherein the at least one proximal curve is configured to prevent motion of the body from being transmitted to the distal tip.

12. The device of claim 1 , wherein the at least one proximal curve is configured to impart a curvature to the cannula.

13. The device of claim 1 , wherein the needle comprises nitinol.

14. The device of claim 1 , wherein the distal tip is beveled.

15. 10. The device of claim 1, wherein the cannula is sufficiently flexible to conform to the anatomy and contours of the patient's eye, yet the cannula has sufficient column strength to allow advancement of the cannula between the sclera and the choroid of the patient's eye without buckling.

16. (a) a needle guide disposed between the needle and the cannula; (b) a support tube disposed partially within the cannula proximal to the needle guide, the support tube extending proximally from the cannula; Further provided with the support tube being more rigid than the needle guide; 10. The apparatus of claim 1.

17. The device of claim 16 , wherein the support tube and the needle guide comprise the same material.

18. The device of claim 1 , wherein the cannula includes a proximal segment including a first material and a distal segment including a second material different from the first material.

19. The device of claim 1 , wherein the at least one proximal curved portion has an arc length in the range of about 16 mm to about 24 mm.

20. The device of claim 1 , wherein the at least one proximal curve has a radius of curvature ranging from about 16 mm to about 24 mm.

21. The device of claim 1 , wherein the at least one distal curved portion has an arc length in the range of about 2.8 mm to about 4.2 mm.

22. The device of claim 1 , wherein the at least one distal curve has a radius of curvature ranging from about 2 mm to about 3 mm.

23. The device of claim 2, wherein the distal straight section has a length in the range of about 0.56 mm to about 0.84 mm.

24. The device of claim 3, wherein the proximal straight section has a length in the range of about 20 mm to about 30 mm.

25. The device of claim 4, wherein the intermediate straight section has a length in the range of about 36.64 mm to about 54.96 mm.

26. (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being dimensioned and configured to be advanced between the sclera and the choroid of the patient's eye; (c) a needle slidably disposed within the cannula, (i) a sharpened distal tip, the needle configured to translate relative to the cannula between a proximal position and a distal position, the distal tip configured to be located inside the cannula when the needle is in the proximal position and the distal tip configured to be located outside the cannula when the needle is in the distal position; (ii) a first curved portion, the needle being resiliently biased to extend through the first curved portion along a first curve; (iii) a second curved portion longitudinally spaced from the first curved portion, the needle being resiliently biased to extend through the second curved portion along a second curve; a needle; An apparatus comprising:

27. (a) a main body; (b) a cannula extending distally from the body, the cannula being flexible, the cannula being dimensioned and configured to be advanced between the sclera and the choroid of the patient's eye, the cannula comprising: (i) a proximal segment having a first cross-sectional area; (ii) an intermediate segment having a second cross-sectional area; (iii) a distal segment having a third cross-sectional area greater than the second cross-sectional area; a cannula including: (c) a needle slidably disposed within the cannula; An apparatus comprising:

28. 28. The apparatus of claim 27, wherein the second cross-sectional area is smaller than the first cross-sectional area.

29. 29. The device of claim 27 or 28, wherein the proximal segment has a first cross-sectional shape, the intermediate segment has a second cross-sectional shape, and the distal segment has a third cross-sectional shape different from the second cross-sectional shape.

30. 28. The device of claim 27, wherein the cannula further comprises a wedge-shaped distal end.

31. 28. The device of claim 27, wherein the proximal segment has a first stiffness and the intermediate segment has a second stiffness different from the first stiffness.

32. 32. The device of claim 31 , wherein the second stiffness is less than the first stiffness.

33. 33. The device of claim 31 or 32, wherein the distal segment has a third stiffness different from the second stiffness.

34. (a) a main body; (b) a cannula extending distally from the body along a length, the cannula being flexible, the cannula being dimensioned and configured to be advanced between the sclera and choroid of a patient's eye, the cannula having a stiffness that varies along the length; (c) a needle slidably disposed within the cannula; An apparatus comprising:

35. The cannula comprises: (i) a proximal segment having a first stiffness; (ii) an intermediate segment having a second stiffness different from the first stiffness; (iii) a distal segment having a third stiffness different from the second stiffness; 35. The apparatus of claim 34, comprising:

36. 36. The device of claim 35, wherein the distal segment comprises a first material and at least one of the proximal segment or the intermediate segment comprises a second material different from the first material.

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