Device for subretinal administration of therapeutic agents via double curved needles

Abstract

The present disclosure provides a device comprising a body, a flexible cannula, and a needle. The cannula is sized and configured to travel between a sclera and a choroid of a patient's eye. The needle is slidably disposed in the cannula and includes a sharp distal tip. The needle translates relative to the cannula between a proximal position and a distal position. The distal tip is positioned inside the cannula when the needle is in the proximal position. The distal tip is positioned outside the cannula when the needle is in the distal position. The needle is resiliently biased to extend along at least one proximal curve through at least one proximal curved needle portion. The needle is resiliently biased to extend along at least one distal curve through at least one distal curved needle portion. The at least one distal curve is different from the at least one proximal curve.

Description

Background Art

[0001] The human eye consists of several layers. The white outer layer is the sclera, which surrounds the choroid layer. The retina is located inside the choroid layer. The sclera contains collagen and elastic fibers, which provide protection for the choroid and retina. The choroid layer includes a vascular system that provides oxygen and nutrients to the retina. The retina includes light-sensitive tissue, including rods and cones. The macula is located in the center of the retina at the back of the eye, usually centered on the axis that passes through the center of the eye's lens and cornea (i.e., the optical axis). The macula provides central vision, particularly through cones.

[0002] Macular degeneration is a medical condition that affects the macula, so that people with macular degeneration may experience loss or degradation of central vision while retaining a certain degree of peripheral vision. Macular degeneration may be caused by a variety of factors, such as age (also known as "AMD") and heredity. Macular degeneration may occur in a "dry" (non-exudative) form, in which cell debris called drusen accumulate between the retina and the choroid, resulting in a map-like atrophic area. Macular degeneration may also occur in a "wet" (exudative) form, in which blood vessels grow out of the choroid behind the retina. Although people with macular degeneration may retain a certain degree of peripheral vision, the loss of central vision may have a huge negative impact on quality of life. In addition, the quality of the remaining peripheral vision may decline, and in some cases may also disappear. Therefore, it may be desirable to provide treatment for macular degeneration to prevent or reverse the vision loss caused by macular degeneration. In some cases, it may be desirable to provide such treatment near the macula in a highly localized manner, such as by delivering a therapeutic substance in the subretinal layers (below the neurosensory layer of the retina and above the retinal pigment epithelium) directly adjacent to the area of ​​geographic atrophy. However, because the macula is located at the back of the eye and beneath delicate layers of the retina, it can be difficult to access the macula in a practical manner.

[0003] While a variety of surgical methods and instruments have been made and used to treat the eye, it is believed that no one prior to the inventors has made or used the invention described in the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0004] While the specification concludes with claims that particularly point out and distinctly claim the technology, it is believed that the technology will be better understood from the following description of certain examples taken in conjunction with the accompanying drawings, in which like reference numerals represent like elements and wherein:

[0005] Figure 1 depicts a perspective view of an example of an apparatus for subretinal administration of a therapeutic agent via a suprachoroidal route;

[0006] Figure 2 Depicted Figure 1A perspective view of a distal portion of a cannula of the device;

[0007] Figure 3 Depicted Figure 2 A front elevation view of a distal portion of a cannula;

[0008] Figure 4 Depicted Figure 2 A top plan view of a distal portion of a cannula;

[0009] Figure 5 Depicted Figure 2 a perspective view of a distal end of a cannula of with a needle extending from the cannula;

[0010] Figure 6 Depicted Figure 1 A three-dimensional image of an apparatus having a medical device combination installed near a patient;

[0011] Fig. 7A A cross-sectional side view of the patient's eye is depicted;

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

[0013] Figure 7C Depicted Fig. 7A A cross-sectional side view of an eye, wherein Figure 2 The cannula is inserted through the sclerotomy opening and between the sclera and choroid of the eye;

[0014] Fig.7D Depicted Fig. 7A a cross-sectional side view of an eye with a distal end of the cannula positioned adjacent to a target location;

[0015] Fig. 7E Depicted Fig. 7A A cross-sectional side view of an eye, wherein Figure 5 The needle is advanced through the choroid to enter the subretinal space at the target location;

[0016] Figure 7F Depicted Fig. 7A A cross-sectional side view of an eye, wherein Figure 5 the needle dispensing a first volume of a guide bubble fluid to provide separation between the retinal region and the choroid at a target location;

[0017] Figure 7G Depicted Fig. 7A A cross-sectional side view of an eye, wherein Figure 5 The needle distributes the therapeutic agent between the retinal area and the choroid at the target location;

[0018] Figure 8 Describes what can be incorporated into Figure 1 A perspective view of an alternative cannula in a device of the present invention, the cannula having a varying stiffness along the length of the cannula;

[0019] Fig. 9 Depicted Figure 8 A front elevation view of a cannula;

[0020] Fig.10 Depicted Figure 8 A side elevation view of the cannula;

[0021] Fig.11 Depicted Figure 8 A top plan view of the cannula;

[0022] Fig.12 Depicts the Fig.11 The line 12-12 intercepts Figure 8 a cross-sectional end view of a middle section of the cannula;

[0023] Fig.13 Depicts the Fig.11 The line 13-13 intercepts Figure 8 a cross-sectional end view of a distal segment of a cannula;

[0024] Fig.14 Describes what can be incorporated into Figure 1 A perspective view of another alternative cannula in a device of the present invention, the cannula having a varying stiffness along the length of the cannula;

[0025] Fig.15 Depicted Fig.14 A front elevation view of a cannula;

[0026] Fig.16 Depicted Fig.14 A side elevation view of the cannula;

[0027] Fig.17 Depicted Fig.14 A top plan view of the cannula;

[0028] Fig.18 Depicts the Fig.17 The line 18-18 intercepts Fig.14 A cross-sectional side view of a cannula;

[0029] Fig.19 Depicts the Fig.17 The line 19-19 intercepts Fig.14 a cross-sectional end view of a proximal segment of a cannula;

[0030] Fig. 20 Depicts the Fig.17The line 20-20 intercepts Fig.14 a cross-sectional end view of a middle section of the cannula;

[0031] Fig.21 Depicts the Fig.17 The line 21-21 intercepts Fig.14 a cross-sectional end view of a middle section of the cannula;

[0032] Fig. 22 Depicts the Fig.17 The line 22-22 intercepts Fig.14 a cross-sectional end view of a distal segment of a cannula;

[0033] Fig.23 Describes what can be incorporated into Figure 1 A side elevation view of an alternative needle in a device of the invention, the needle having a proximal curved portion and a distal curved portion;

[0034] Fig.24 Depicted Fig.23 a side elevation view of the distal end of the needle;

[0035] Fig.25 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the present invention, the needle having a proximal curved portion and a distal curved portion;

[0036] Fig.26 Depicted Fig.25 a side elevation view of the distal end of the needle;

[0037] Fig. 27 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the present invention, the needle having a proximal curved portion and a distal curved portion;

[0038] Fig.28 Depicted Fig. 27 a side elevation view of the distal end of the needle;

[0039] Fig.29 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the invention, the needle having a first proximal curved portion and a second proximal curved portion and a distal curved portion;

[0040] Fig.30 Depicted Fig.29 a side elevation view of the distal end of the needle;

[0041] Fig.31 Depicted Fig.29 A side elevation view of a needle showing a first reference circle for a first proximal curved portion;

[0042] Fig.32 Depicted Fig.29 a side elevation view of the needle of , showing a second reference circle for a second proximal curved portion;

[0043] Fig.33 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the present invention, the needle having a first distal curved portion and a second distal curved portion;

[0044] Fig.34 Depicted Fig.33 a side elevation view of the distal end of the needle;

[0045] Fig.35 Depicted Fig.33 A side elevation view of a needle showing a reference circle for a first distal curved portion;

[0046] Fig.36 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the present invention, the needle having a proximal curved portion and a first distal curved portion and a second distal curved portion;

[0047] Fig.37 Depicted Fig.36 a side elevation view of the distal end of the needle;

[0048] Fig.38 Describes what can be incorporated into Figure 1 A side elevation view of another alternative needle in a device of the invention, the needle having first and second proximal curves and first and second distal curves; and

[0049] Fig.39 Depicted Fig.38 Side elevation view of the distal end of the needle.

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

[0051] The following description of certain 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 description, which is intended to illustrate one of the best modes for implementing the present technology. As will be appreciated, the technology described herein can have other different and obvious aspects, all without departing from the present technology. Therefore, the drawings and descriptions should be considered to be illustrative rather than restrictive in nature.

[0052] It should also 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. Therefore, the teachings, expressions, embodiments, examples, etc. described below should not be viewed in isolation from each other. In view of the teachings herein, various suitable ways in which the teachings herein may be combined will be apparent to those skilled in the art. Such modifications and variations are intended to be included within the scope of the claims.

[0053] For clarity of disclosure, the terms "proximal" and "distal" are defined herein relative to a surgeon or other operator grasping a surgical instrument having a distal surgical end effector. The term "proximal" refers to a position where an element is closer to the surgeon or other operator, and the term "distal" refers to a position where an element is 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 used herein in conjunction with any numerical values ​​or ranges of values ​​are intended to encompass the precise value or values ​​recited and a suitable tolerance such that the recited feature or combination of features can be used for the intended purpose described herein.

[0055] I. Devices for Subretinal Administration of Therapeutic Agents

[0056] Figure 1 An example of an apparatus (100) is shown that is configured to be used in a procedure for administering a therapeutic agent subretinal to a patient's eye via a suprachoroidal approach. The apparatus (100) includes a body (110) and a flexible cannula (130) extending distally from the body (110). The cannula (130) of the present example has a generally rectangular cross-section, but any other suitable cross-sectional profile (e.g., elliptical, etc.) may also be used. The generally rectangular cross-sectional profile of the cannula (130) is configured to enable the cannula (130) to pass along the suprachoroidal space without damage, as will be described in more detail below. The cannula (130) is typically configured to support a needle (150) that can slide within the cannula (130), as will be described in more detail below.

[0057] In the present example, 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, cannula (130) has a cross-sectional profile dimension 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 the present example is flexible enough to conform to the specific structure and contours of a patient's eye, yet the cannula (130) also has sufficient column strength to permit the cannula (130) to travel between the sclera and choroid of the patient's eye without buckling. As in Figures 2 to 5 As best seen in the , cannula (130) includes a transversely oriented opening (134) near the distal end (132) of the cannula (130). The opening (134) of the present example is formed by a U-shaped side recess (136) in the cannula (130) that leads to an open distal end (138) of the guide needle lumen within the cannula (130). The distal end (132) is atraumatic such that the distal end (132) is configured to provide separation between the sclera and choroidal layers via blunt dissection, as will be described in greater detail below, thereby enabling the cannula (130) to advance between such layers without causing trauma to the sclera or choroidal layers.

[0058] By way of example only, cannula (130) may be constructed and operated in accordance with at least some of the teachings of the following and / or in any other suitable manner: U.S. Patent No. 10,226,379, issued on March 12, 2019, entitled “Method and Apparatus for Subretinal Administration of Therapeutic Agent,” the disclosure of which is incorporated herein by reference in its entirety; U.S. Patent No. 10,646,374, issued on May 12, 2020, entitled “Apparatus and Method to From Entry Bleb for Subretinal Delivery of Therapeutic Agent,” the disclosure of which is incorporated herein by reference in its entirety.

[0059] As in Figure 5As shown in , the needle (150) can advance distally to protrude from the opening (134). The needle (150) of this example has a sharp distal tip (152) and defines a lumen (not shown). The distal tip (152) of this example has a lancet structure. In some other versions, the distal tip (152) has a three-bevel structure or any other structure as described in U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. In view of the teachings herein, other other suitable forms that the distal tip (152) can take will be apparent to those skilled in the art. In this example, when the cannula (130) is disposed in the suprachoroidal space, the substantially rectangular, substantially elliptical or other substantially flat cross-sectional profile of the cannula (130) prevents the cannula (130) from rotating around the longitudinal axis of the cannula (130), as will be described in more detail below. This provides a consistent and predictable orientation of opening ( 134 ), thereby providing a consistent and predictable exit path for needle ( 150 ) as needle ( 150 ) is advanced distally relative to cannula ( 130 ), as will be described in greater detail below.

[0060] By way of example only, after needle (150) has been 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); or more specifically, in the range of about 7° and about 9° relative to the longitudinal axis of cannula (130). In the present example, needle (150) is resiliently biased to assume a curved configuration, thereby providing an exit angle that varies based on the extent to which needle (150) has been advanced distally relative to cannula (130). As just another example, needle (150) may include a preformed bend in accordance with at least some of the teachings of U.S. Patent No. 10,478,553, issued on November 19, 2019, and entitled “Apparatus for Subretinal Administration of Therapeutic Agent via a Curved Needle,” the disclosure of which is incorporated herein by reference in its entirety.

[0061] As in Figure 1As shown in , the instrument (100) of the present example further includes an actuation knob (120) located at the top portion (114) of the body (110). The actuation knob (120) can be rotated relative to the body (110) to selectively translate the needle (150) longitudinally relative to the cannula (130). Specifically, the actuation knob (120) can be rotated in a first angular direction to drive the needle (150) distally relative to the cannula (130); and rotated in a second angular direction to drive the needle (150) proximally relative to the cannula (130). By way of example only, the instrument (100) can provide such functionality through the knob (120) in accordance with at least some of the teachings of U.S. Patent No. 10,646,374, the disclosure of which is incorporated herein by reference in its entirety. In view of the teachings herein, other suitable ways in which the rotational motion of the knob (120) can be converted into a linear translation of the needle (150) will be apparent to those skilled in the art. Similarly, other suitable ways in which needle (150) may be actuated (150) longitudinally relative to cannula (130) will be apparent to those of ordinary skill in the art in view of the teachings herein. Figure 1 As shown in , catheter assembly (140) extends proximally from body (110). Catheter assembly (140) is configured to include one or more fluid conduits (not shown) in fluid communication with needle (150). In some versions, such fluid conduits are coupled to a source of guiding bubble fluid and therapeutic agent.

[0062] II. Procedures for delivering therapeutic agents to the subretinal space via the suprachoroidal route

[0063] Figure 6The apparatus (100) is shown positioned relative to a patient. In this example, a surgical sheet (12) is placed on the patient, wherein an opening (18) is formed in the surgical sheet (12) near the patient's eye (301). A speculum (16) is used to hold the eye (301) open. A fixture (14) is positioned adjacent to the eye (301). The fixture (14) can be used to secure an apparatus, such as a viewing mirror, relative to the patient. A magnetic pad (30) is adhered to the surgical sheet (12) adjacent to the opening (18) adjacent to the eye (301). The apparatus (100) is placed on the magnetic pad (30) and is removably secured to the magnetic pad via magnetic attraction. In this example, one or more permanent magnets (not shown) are positioned within the body (110), near the bottom portion (112); and these magnets are magnetically attracted to one or more ferrous elements (not shown) contained within the magnetic pad (30). By way of example only, these magnets and magnetic pads (30) may be constructed in accordance with at least some of the teachings of U.S. Patent No. 10,806,629, issued on October 20, 2020, entitled "Injection Device for Subretinal Delivery of Therapeutic Agent," the disclosure of which is incorporated herein by reference in its entirety. The instrument (100) is oriented to enable the flexible cannula (130) of the instrument (100) to be inserted into the eye (301). An example of a process for inserting and positioning the cannula (130) in the eye (301) will be described below with reference to 7A to 7F Describe in more detail.

[0064] In the present example, the apparatus (100) is coupled to a fluid delivery system (80) via a catheter assembly (140). In this example, the fluid delivery system (80) includes a bubble fluid source (82) and a therapeutic fluid source (84). The bubble fluid source (82) is coupled to the bubble fluid catheter (142) of the catheter assembly (140); and the therapeutic fluid source (84) is coupled to the therapeutic agent catheter (144) of the catheter assembly (140). The catheters (142, 144) are in fluid communication with the needle (150). In some versions, the fluid sources (82, 84) include syringes. In some other versions, the fluid sources (82, 84) include separate reservoirs and one or more associated pumps and / or valves, etc.

[0065] FIG. 7A to FIG. 7GAn example of a procedure that can be performed using the apparatus described above to deliver a therapeutic agent to the subretinal space of an eye (301) via a suprachoroidal approach is shown. By way of example only, the methods described herein can be used to treat macular degeneration and / or other ocular conditions. Although the procedures described herein are discussed in the context of treating age-related macular degeneration, such limitation is not intended or implied. For example, in some alternative procedures, the same techniques described herein can be used to treat retinitis pigmentosa, diabetic retinopathy, and / or other ocular conditions. Additionally, the procedures described herein can be used to treat other conditions such as dry or wet age-related macular degeneration.

[0066] In the present example, the procedure begins with the operator immobilizing the tissue (e.g., eyelid) surrounding the patient's eye (301) using an instrument such as a speculum (16), and / or any other instrument suitable for immobilization. Although immobilization is described herein with reference to the tissue surrounding the eye (301), the eye (301) itself may remain free to move. As in Fig. 7A As shown in , once the tissue surrounding the eye (301) is secured, an eye chandelier port (314) is inserted into the eye (301) to provide intraocular illumination while viewing the interior of the eye (301) through the pupil. In the present example, the eye chandelier port (314) is positioned in the inferior medial quadrant so that a superior temporal quadrant 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 an area of ​​the eye (301) that is targeted for delivery of a therapeutic agent.

[0067] In this example, Fig. 7A At the stage shown in , only the chandelier port (314) has been inserted, and the optical fiber (315) has not yet been inserted into the port (314). In some other versions, the optical fiber (315) may be inserted into the chandelier port (314) at this stage. In either case, the eye may optionally be visually inspected using a microscope to confirm proper positioning of the eye's chandelier port (314) relative to the target site. Although Fig. 7A A particular positioning of eye chandelier port (314) is shown, though eye chandelier port (314) may have any other suitable positioning as would be apparent to one of ordinary skill in the art in view of the teachings herein.

[0068] Once the eye chandelier port (314) has been positioned, the conjunctiva may be dissected by cutting a flap in the conjunctiva and pulling the flap back to access the sclera (304). After such dissection is completed, the exposed surface of the sclera (304) may optionally be cauterized using a cautery tool to blanch it to minimize bleeding. Once the conjunctival dissection is complete, the exposed surface of the sclera (304) may optionally be dried using a WECK-CEL or other suitable absorptive device.

[0069] The template can then be used to mark the eye (20), as described in: U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety; and / or U.S. Patent No. 11,000,410, issued on May 11, 2021, entitled "Guide Apparatus for Tangential Entry into Suprachoroidal Space," the disclosure of which is incorporated herein by reference in its entirety. The operator can then use the visual guide created using the template to attach the suture loop assembly (332) and perform a sclerotomy using a conventional scalpel (313) or other suitable cutting instrument, such as in Figure 7B As an example only, the suture loop assembly (332) can be formed in accordance with at least some of the teachings of U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. Alternatively, in lieu of the suture loop assembly (332), the operator can install a guide tack in accordance with at least some of the teachings of U.S. Patent No. 11,000,410, the disclosure of which is incorporated herein by reference in its entirety.

[0070] The sclerotomy procedure forms a small incision through the sclera (304) of the eye (301). Special care is taken when performing the sclerotomy 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 is made in the eye (301), a blunt dissection may optionally be performed to partially separate the sclera (304) from the choroid (306). Such a dissection may be performed using a small, blunt, elongated instrument, as will be apparent to one of skill in the art in view of the teachings herein.

[0071] As the sclerotomy procedure progresses, the operator may insert the cannula (130) of the instrument (100) through the incision and into the space between the sclera (304) and the choroid (306). Figure 7CAs can be seen in the figure, the cannula (130) is guided through the suture loop assembly (332) and enters the incision. The suture loop assembly (332) can stabilize the cannula (130) during insertion. In addition, the suture loop assembly (332) maintains the cannula (130) in an orientation that is substantially tangential to the incision. When the cannula (130) is guided through the incision, such a tangential orientation can reduce trauma. When the cannula (130) is inserted into the incision through the suture loop assembly (332), the operator can 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 only optional and can be omitted in some instances. As described above, a guide pin (or other device) can be used instead 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 cavity on the opposite side of the choroid (306). Various suitable ways to visualize distal end ( 132 ) in order to observe proper positioning of distal end ( 132 ) will be apparent to those of ordinary skill in the art in view of the teachings herein.

[0072] Although not shown, in some examples, cannula (130) may include one or more markings on a surface of cannula (130) to indicate various insertion depths. While merely optional, such markings may be desirable to assist an operator in identifying the proper insertion depth as cannula (130) is guided along an atraumatic path. For example, an operator may visually observe the position of such markings 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 cannula (130) has been inserted into eye (301). By way of example only, one such marking may correspond to an insertion depth of approximately 6 mm for cannula (130).

[0073] As in Fig.7D As shown in , once the cannula (130) is at least partially inserted into the eye (301), the operator can insert the optical fiber (315) into the eye chandelier port (314) if the optical fiber (315) has not been inserted at this stage. With the eye chandelier port (314) in place and assembled with the optical fiber (315), the operator can activate the eye chandelier port (314) by directing light through the optical fiber (315) to provide illumination of the eye (301) and thereby visualize the interior of the eye (301). The positioning of the cannula (130) can optionally be further adjusted at this time to ensure proper positioning of the geographic atrophy area relative to the retina (308). In some cases, the operator may wish to rotate the eye (301), such as by pulling on the suture loop assembly (332), to direct the pupil of the eye (301) toward the operator in order to optimize visualization of the interior of the eye (301) via the pupil.

[0074] FIG. 7C to FIG. 7D The cannula (130) is shown as it is guided between the sclera (304) and the choroid (306) to position the distal end (132) of the cannula (130) at a delivery site for a therapeutic agent. In this example, the delivery site corresponds to a generally posterior region of an area of ​​geographic atrophy adjacent to the retina (308) in the eye (301). Specifically, the delivery site of this example is above the macula, in the potential space between the neurosensory retina and the retinal pigment epithelium. By way of example only, when the cannula (130) is in FIG. 7C to FIG. 7D While traveling within the range of motion shown in , the operator can rely on direct visualization through a microscope aimed at the pupil of the eye (301), with illumination provided by optical fibers (315) and port (314). The cannula (130) can 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 transmit visible light through the distal end of the cannula (130).

[0075] Once the cannula (130) has been Fig.7D Once the needle (150) of the device (100) has been advanced to the delivery site as shown in FIG. 1 , the operator may then advance the needle (150) of the device (100) by actuating knob (120) as described above. Fig. 7E , the needle (150) is advanced relative to the cannula (130) such that the needle (150) pierces the choroid (306) without penetrating the retina (308). Just prior to penetrating the choroid (306), the needle (150) may appear under direct visualization to "bulge" the surface of the choroid (306). In other words, the needle (150) may deform the choroid (306) by pushing the choroid (306) upward, thereby providing an appearance similar to a tent pole deforming the top of a tent. An operator may use such visual phenomena to identify whether the choroid (306) will be pierced and the location of any eventual piercing. The particular amount of needle (150) travel sufficient to initiate "bulging" and subsequent piercing of the choroid (306) may be any suitable amount, as may be determined by a variety of factors, such as, but not limited to, general patient anatomy, local patient anatomy, operator preference, and / or other factors. As described above, examples of the range of needle (150) travel may be between approximately 0.25 mm and approximately 10 mm; or more specifically, between approximately 2 mm and approximately 6 mm.

[0076] In the present example, after the operator has confirmed that needle (150) has been properly advanced by visualizing the bulging effect described above, the operator infuses a balanced salt solution (BSS) or other similar solution as needle (150) is advanced relative to cannula (130). Such BSS may form a guide bubble (340) in front of needle (150) as needle (150) is advanced through choroid (306). Guide bubble (340) may be desirable for two reasons. First, as in Figure 7F As shown in , the guide bubble (340) can provide a further visual indicator to the operator to indicate when the needle (150) is properly positioned at the delivery site. Secondly, once the needle (150) has penetrated the choroid (306), the guide bubble (340) can provide a barrier between the needle (150) and the retina (308). Such a barrier can push the retinal wall outward, thereby minimizing the risk of retinal perforation when the needle (150) travels to the delivery site. In some versions, a foot pedal is actuated to drive the guide bubble (340) out of the needle (150). Alternatively, in view of the teachings of this article, other suitable features that can be used to drive the guide bubble (340) out of the needle (150) will be apparent to those skilled in the art.

[0077] Once the operator visualizes the guide bubble (340), the operator can terminate the infusion of BSS, leaving the Figure 7F . Next, the therapeutic agent (342) may be infused by actuating the fluid delivery system (80) or some other fluid delivery device as described in 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 activators, and / or any other suitable therapeutic agent as would be apparent to one of skill 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, issued August 19, 2008, entitled “Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells,” the disclosure of which is incorporated herein by reference in its entirety. In addition to or as an alternative to being used to deliver therapeutic agents (342), device (100) and variations thereof may be used to provide drainage and / or perform other procedures.

[0078] In the present example, the amount of therapeutic agent (342) ultimately delivered to the delivery site is approximately 50 μL, but any other suitable amount may be delivered. In some versions, a foot pedal is actuated to drive the agent (342) out of the needle (150). Alternatively, other suitable features that may be used to drive the agent (342) out of the needle (150) will be apparent to those of skill in the art in view of the teachings herein. The delivery of the therapeutic agent (342) may be visualized by the expansion of the fluid bag, such as in FIG. Figure 7G As shown, when the therapeutic agent (342) is injected into the subretinal space, the therapeutic agent (342) is substantially mixed with the fluid of the guide bubble (340).

[0079] Once delivery is complete, the needle (150) can be retracted by rotating the knob (120) in the direction opposite to the direction used to advance the needle (150); and the cannula (130) can 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, such 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) can be removed, and the incision in the sclera (304) can be closed using any suitable conventional technique.

[0080] As described above, the aforementioned surgery can be performed to treat patients with macular degeneration. In some such cases, the therapeutic agent (342) delivered by the needle (150) can include cells derived from the postpartum umbilical cord and placenta. As described above, and by way of example only, the therapeutic agent (342) can be provided according to 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, in addition to or in place of the substances described in U.S. Patent No. 7,413,734 and / or elsewhere herein, the needle (150) can be used to deliver one or more other suitable substances. By way of example only, the therapeutic agent (342) can include various drugs, including but not limited to small molecules, macromolecules, cells and / or gene therapies. It should also be understood that macular degeneration is only an illustrative example of a disorder that can be treated by the surgery described herein. Other biological disorders that can be addressed using the instruments and surgeries described herein will be apparent to those of ordinary skill in the art.

[0081] The procedure described above may be performed in accordance with any of the teachings of: U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety; U.S. Patent No. 9,949,874, issued on April 24, 2018, entitled “Therapeutic Agent Delivery Device with Convergent Lumen,” the disclosure of which is incorporated herein by reference in its entirety; U.S. Patent No. 9,925,088, issued on March 27, 2018, entitled “Sub-Retinal Tangential Needle Catheter Guide and Introducer,” the disclosure of which is incorporated herein by reference in its entirety; U.S. Patent No. 10,322,028, issued on June 18, 2019, entitled “Method and Apparatus for Sensing Position Between Layers of an Eye,” the disclosure of which is incorporated herein by reference in its entirety; U.S. Patent No. 10,322,028, issued on September 4, 2018, entitled “Motorized Suprachoroidal Injection of No. 10,064,752, entitled “Therapeutic Agent”, the disclosure of which is incorporated herein by reference in its entirety; No. 10,219,936, issued on March 5, 2019, entitled “Therapeutic Agent Delivery Device with Advanceable Cannula and Needle”, the disclosure of which is incorporated herein by reference in its entirety; No. 10,258,502, issued on April 16, 2019, entitled “Therapeutic Agent Delivery Device”, the disclosure of which is incorporated herein by reference in its entirety; and / or International Publication No. WO 2022 / 136913, published on June 30, 2022, entitled “Ocular Cannula Guide”, the disclosure of which is incorporated herein by reference in its entirety.

[0082] III. Examples of Alternative Cannulas for Instrumentation

[0083] In some cases, it may be desirable to provide cannula (130) with an atraumatic wedge-shaped distal end, such as to aid in the insertion of cannula (130) through a sclerotomy incision and into the space between the sclera (304) and the choroid (306). It should be appreciated that such a wedge-shaped distal end may improve the ability of cannula (130) to provide separation between the sclera (304) and choroid (306) layers via blunt dissection, and may thereby improve the ability of cannula (130) to advance between such layers without causing trauma to the sclera or choroid layers.

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

[0085] Additionally or alternatively, it may be desirable to provide a cannula (130) having a varying stiffness along the length of the cannula (130). For example, it may be desirable to provide a distal segment having a relatively high stiffness near the distal end of the cannula (130) so as to reduce any curvature that may otherwise be imparted to the cannula (130) by the needle (150) as the needle (150) is retracted into the cannula (130) (e.g., where the needle (150) includes a preformed bend and / or curve), and thereby facilitate atraumatic passage of the cannula (130) along the suprachoroidal space as the needle (150) is retracted therein; and to provide the cannula (130) with a relatively low stiffness intermediate segment proximal to the distal segment so as to enhance the ability of the cannula (130) to conform to the specific structure and contours of the eye (301).

[0086] A. First Example of Alternative Cannula with Variable Stiffness

[0087] Figures 8 to 13An example of a cannula (430) is shown that can function in this manner and can be easily incorporated into the device (100) in place of the cannula (130). The cannula (430) can be similar to the cannula (130), except as described below. For example, as with the cannula (130), the cannula (430) is flexible enough to conform to the specific structure and contour of the patient's eye; however, the cannula (430) also has sufficient column strength to permit the cannula (430) to travel between the sclera and choroid of the eye (301) without buckling. In some versions, the cannula (430) includes a flexible material having a hardness greater than the hardness of the flexible material of the cannula (130). For example, the cannula (430) can include a flexible material having a hardness greater than the hardness of a polyether block amide (PEBA), but any other suitable material or combination of materials can also be used.

[0088] The cannula (430) of the present example includes a distal end (432) and a distally facing opening (434) near the distal end (432). The opening (434) of the present example is adjacent to a U-shaped side recess (436) in the cannula (430) that leads to an open distal end (438) of a guide needle lumen (439) within the cannula (430). The opening (434) is spaced proximally from the tip of the distal end (432); and the side recess (436) extends a 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, the opening (434) is oriented along a plane that is oriented obliquely relative to the longitudinal axis of the cannula (430). In either case, due to the location and configuration of opening (434) in combination with side recess (436), cannula (430) can be viewed as providing a laterally oriented path for needle (550, 650, 750, 850, 950, 1050, 1150) to exit cannula (430) as needle (550, 650, 750, 850, 950, 1050, 1150) advances 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 enabling the cannula (430) to travel between such layers without causing trauma to the sclera or choroid layers. In this regard, the distal end (432) of the present example is defined by a lower surface (433) extending longitudinally and an upper surface (435) extending obliquely and tapering downwardly in a distal direction toward the lower surface (433), such that the distal end (432) is generally wedge-shaped. As shown, in the present example, a U-shaped side recess (436) extends through the upper surface (435) of the distal end (432). It should be understood that the distal end (432) can be configured to be wedge-shaped in any other suitable manner. As described above, the wedge shape of the distal end (432) can improve the ability of the cannula (430) to provide separation between the sclera (304) and choroid (306) layers via blunt dissection, and can thereby improve the ability of the cannula (430) to advance between such layers without causing trauma to the sclera (304) and choroid (306) layers. The wedge shape of the distal end (432) can also assist in maintaining the angular orientation of the distal end (432) of the cannula (430) relative to the longitudinal axis of the cannula (430) as the cannula (430) advances between the sclera (304) and choroid (306) layers toward the posterior region of the eye (301). In other words, as the needle (150, 550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (430), the wedge shape of the distal end (432) can assist in maintaining the orientation of the side recess (436) toward the interior region of the eye (301), thereby promoting proper trajectory of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301).

[0090] In the example shown, cannula (430) has a varying cross-sectional area along the length of cannula (430), such that cannula (430) may also have a varying stiffness along the length of cannula (430). Figure 8 and Figure 10 to Figure 11 As best shown in , the cannula (430) of the present example includes a proximal segment (430p), a middle segment (430m), and a distal segment (430d). In the example shown, the distal segment (430d) is immediately proximal to the wedge-shaped distal end (432) of the cannula (430) such that the upper and lower surfaces of the distal segment (430d) directly and continuously interface with the upper and lower surfaces (433, 435) of the distal end (432), respectively.

[0091] The proximal segment (430p) can have a generally rectangular (e.g., oblong) cross-sectional profile and a first cross-sectional area, and can be configured to be manipulated by an operator to push and pull the intermediate and distal segments (430m, 430d) during use. Although the proximal segment (430p) of the present example has a generally rectangular cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may also be used.

[0092] As in Fig.12 As shown in , the middle section (430m) has a generally diamond-shaped cross-sectional profile and a second cross-sectional area that is less than the first cross-sectional area. In this regard, the cannula (430) can taper inward laterally and / or transversely from the proximal section (430p) to the middle section (430m). Although the middle section (430m) of the present example has a generally diamond-shaped cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., rectangular, elliptical, etc.) can also be used. It should be understood that the reduced cross-sectional area of ​​the middle section (430m) relative to the proximal section (430p) can provide the middle section (430m) with a lower stiffness than the proximal section (430p), thereby helping to vary the stiffness of the cannula (430) along the length of the cannula (430). As described above, the relatively low stiffness of the middle section (430m) can improve the ability of the cannula (430) to conform to the specific structure and profile of the eye (301). In some versions, the length of middle segment (430m) is greater than the length of each of the proximal and distal segments (430p, 430d). For example, the length of middle segment (430m) may be greater than the combined length of the proximal and distal segments (430p, 430d) and may comprise a majority of the overall length of cannula (430).

[0093] As in Fig.13 As shown in , the distal segment (430d) has a generally rectangular (e.g., oblong) cross-sectional profile and a third cross-sectional area greater than the second cross-sectional area. In this regard, the cannula (430) can taper outward laterally and / or transversely from the middle segment (430m) to the distal segment (430d). In some versions, the third cross-sectional area can be smaller than the first cross-sectional area. Although the distal segment (430d) of the present example has a generally rectangular cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) can also be used.

[0094] It should be appreciated that the increased cross-sectional area of ​​the distal segment (430d) relative to the middle segment (430m) can provide the distal segment (430d) with a stiffness that is higher than the stiffness of the middle segment (430m), thereby facilitating the stiffness of the cannula (430) to vary along the length of the cannula (430). In some versions, the distal segment (430d) of the cannula (430) can have a cross-sectional area that is substantially equal to the cross-sectional area of ​​the cannula (130). For example, the width of the distal segment (430d) can range from about 1.28 mm to about 1.92 mm; or more specifically can be about 1.6 mm; and / or the height of the distal segment (430d) can range from about 0.48 mm to about 0.72 mm; or more specifically can be about 0.6 mm. As described above, the cannula (430) can also include a flexible material having a stiffness greater than the stiffness of the material of the cannula (130). Thus, the distal segment (430d) of the cannula (430) may have an increased stiffness relative to the stiffness of the cannula (130). For example, the distal segment (430d) may have a stiffness that is higher than the stiffness of the cannula (130) at or near the distal end (132) of the cannula (130). As described above, 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 needle (150)) that is retracted into the cannula (430), and thereby facilitate atraumatic passage of the cannula (430) along the suprachoroidal space when the needle (150) is retracted therein.

[0095] In the present example, the substantially rectangular, substantially elliptical, or other substantially flat cross-sectional profile of distal segment (430d) of cannula (430) prevents cannula (430) from rotating about the longitudinal axis of cannula (430) when cannula (430) is disposed in the suprachoroidal space.

[0096] In other words, as the needle (550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (430), the cross-sectional profile of the distal segment (430d) of the cannula (430) can assist in maintaining the orientation of the side recess (436) toward the internal region of the eye (301), thereby facilitating proper trajectory of the needle (550, 650, 750, 850, 950, 1050, 1150) toward the internal region of the eye (301). Thus, the wedge shape of the distal end (432) combined with the cross-sectional profile of the distal segment (430d) can 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) is advanced distally relative to the cannula (430). The cross-sectional profiles of the proximal segment (430p) and / or the intermediate segment (430m) can provide a similar effect.

[0097] In the example shown, the needle guide (441) is disposed within the needle guide lumen (439) of the cannula (430). The needle guide (441) can be fixed within the needle guide lumen (439) of the cannula (430) by a press fit or an interference fit, by an adhesive, by a mechanical locking mechanism, and / or in any other suitable manner. In the present example, the needle guide (441) is formed of a polyimide material, but it should be understood that one or more other suitable biocompatible materials can be used, such as one or more other suitable biocompatible materials having a hardness less than that of stainless steel. The needle guide (441) of the present example is substantially straight, but can bend with the cannula (430). The needle guide (441) defines a needle lumen (443) that is configured to slidably receive a needle, such as any of the needles (150, 550, 650, 750, 850, 950, 1050, 1150) described herein. As discussed above, the relatively low durometer of the material of needle guide (441) may enhance the ability of cannula (430) to conform to the specific structure and contours of eye (301).

[0098] B. Second Example of Alternative Cannulas with Different Stiffnesses

[0099] Figures 14 to 22 Another example of a cannula (530) is shown that can function in the manner described above and can be easily incorporated into the device (100) in place of the cannula (130). The cannula (530) can be similar to the cannula (430), except as described below. For example, as with the cannula (430), the cannula (530) is flexible enough to conform to the specific structure and contour of the patient's eye; however, the cannula (530) also has sufficient column strength to permit the cannula (530) to travel between the sclera and choroid of the eye (301) without buckling. In some versions, the cannula (530) includes a flexible material having a hardness greater than the hardness of the flexible material of the cannula (130). For example, the cannula (530) can include a flexible material having a hardness greater than the hardness of a polyether block amide (PEBA), but any other suitable material or combination of materials can also be used.

[0100] The cannula (530) of the present example includes a distal end (532) and a distally facing opening (534) near the distal end (532). The opening (534) of the present example is adjacent to a U-shaped side recess (536) in the cannula (530) that leads to an open distal end (538) of a guide needle lumen (539) within the cannula (530). The opening (534) is proximally spaced a first distance (D1) from the tip of the distal end (532); and the side recess (536) extends a length from the opening (534) to the tip of the distal end (532). By way of example only, the first distance (D1) can 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, the opening (534) is oriented along a plane that is oriented obliquely relative to the longitudinal axis of the cannula (530). In either case, due to the location and configuration of opening (534) in combination with side recess (536), cannula (530) can be viewed as providing a laterally oriented path for needle (550, 650, 750, 850, 950, 1050, 1150) to exit cannula (530) as the 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 provide separation between the sclera (304) and choroid (306) layers via blunt dissection, thereby enabling the cannula (530) to travel between such layers without causing trauma to the sclera or choroid layers. In this regard, the distal end (532) of the present example is defined by a lower surface (533) extending longitudinally and an upper surface (535) extending obliquely and tapering downwardly in a distal direction toward the lower surface (533), such that the distal end (532) is generally wedge-shaped. As shown, in the present example, a U-shaped side recess (536) extends through the upper surface (535) of the distal end (532). It should be understood that the distal end (532) can be configured to be wedge-shaped in any other suitable manner. As described above, the wedge shape of the distal end (532) can improve the ability of the cannula (530) to provide separation between the sclera (304) and choroid (306) layers via blunt dissection, and can thereby improve the ability of the cannula (530) to advance between such layers without causing trauma to the sclera (304) and choroid (306) layers. The wedge shape of the distal end (532) can also assist in maintaining the angular orientation of the distal end (532) of the cannula (530) relative to the longitudinal axis of the cannula (530) as the cannula (530) advances between the sclera (304) and choroid (306) layers toward the posterior region of the eye (301). In other words, as the needle (150, 550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (530), the wedge shape of the distal end (532) can assist in maintaining the orientation of the side recess (536) toward the interior region of the eye (301), thereby promoting proper trajectory of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) toward the interior region of the eye (301).

[0102] In the example shown, cannula (530) has a varying cross-sectional area along the length of cannula (530), such that cannula (530) may also have a varying stiffness along the length of cannula (530). Fig.14 and Figures 16 to 18As best shown in , the cannula (530) of the present example includes a proximal segment (530p), a middle segment (530m), and a distal segment (530d). In the example shown, the distal segment (530d) is immediately proximal to the wedge-shaped distal end (532) of the cannula (530) such that the upper and lower surfaces of the distal segment (530d) directly and continuously interface with the upper and lower surfaces (533, 535) of the distal end (532), respectively. More specifically, the distal segment (530d) extends between a distal terminal proximally spaced a second distance (D2) from the tip of the distal end (532) and a proximal terminal proximally spaced a third distance (D3) from the tip of the distal end (532); the intermediate segment (530m) extends between a distal terminal proximally spaced a third distance (D3) from the tip of the distal end (532) and a proximal terminal proximally spaced a fourth distance (D4) from the tip of the distal end (532); and the proximal segment (530p) extends from a distal terminal proximally spaced a fifth distance (D5) 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] As in Fig.19 As shown in , the proximal segment (530p) has a generally rectangular (e.g., oblong) cross-sectional profile and a first cross-sectional area, and can be configured to be manipulated by an operator to push and pull the middle and distal segments (530m, 530d) during use. Although the proximal segment (530p) of the present example has a generally rectangular cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) may also be used.

[0104] As in Figure 20 to Figure 21As shown in , the middle section (530m) has a generally diamond-shaped cross-sectional profile and a second cross-sectional area that is less than the first cross-sectional area. In this regard, the cannula (530) can taper inward laterally and / or transversely from the proximal section (530p) to the middle section (530m). Although the middle section (530m) of the present example has a generally diamond-shaped cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., rectangular, elliptical, etc.) can also be used. It should be understood that the reduced cross-sectional area of ​​the middle section (530m) relative to the proximal section (530p) can provide the middle section (530m) with a lower stiffness than the proximal section (530p), thereby facilitating the stiffness of the cannula (530) to vary along the length of the cannula (530). As described above, the relatively low stiffness of the middle section (530m) can improve the ability of the cannula (530) to conform to the specific structure and profile of the eye (301). In some versions, the length of middle segment (530m) is greater than the length of each of the proximal and distal segments (530p, 530d). For example, the length of middle segment (530m) may be greater than the combined length of the proximal and distal segments (530p, 530d) and may comprise a majority of the overall length of cannula (530).

[0105] As in Fig. 22 As shown in , the distal segment (530d) has a generally rectangular (e.g., oblong) cross-sectional profile and a third cross-sectional area greater than the second cross-sectional area. In this regard, the cannula (530) can taper outward laterally and / or transversely from the middle segment (530m) to the distal segment (530d). In some versions, the third cross-sectional area can be smaller than the first cross-sectional area. Although the distal segment (530d) of the present example has a generally rectangular cross-sectional profile, it should be understood that any other suitable cross-sectional profile (e.g., elliptical, etc.) can also be used.

[0106] It should be appreciated that the increased cross-sectional area of ​​the distal segment (530d) relative to the middle segment (530m) can provide the distal segment (530d) with a stiffness that is higher than the stiffness of the middle segment (530m), thereby facilitating the stiffness of the cannula (530) to vary along the length of the cannula (530). In some versions, the distal segment (530d) of the cannula (530) can have a cross-sectional area that is substantially equal to the cross-sectional area of ​​the cannula (130). For example, the width of the distal segment (530d) can range from about 1.28 mm to about 1.92 mm; or more specifically can be about 1.6 mm; and / or the height of the distal segment (530d) can range from about 0.48 mm to about 0.72 mm; or more specifically can be about 0.6 mm. As described above, the cannula (530) can also include a flexible material having a stiffness greater than the stiffness of the material of the cannula (130). Thus, the distal segment (530d) of the cannula (530) can have an increased stiffness relative to the stiffness of the cannula (130). For example, the distal segment (530d) can have a stiffness that is higher than the stiffness of the cannula (130) at or near the distal end (132) of the cannula (130). Additionally or alternatively, the distal segment (530d) and / or the distal end (532) can include a flexible material having a stiffness that is greater than the stiffness of the proximal segment (530p) and / or the middle segment (530m). For example, the distal segment (530d) and / or the distal end (532) can include a first grade polyether block amide (PEBA) having a first stiffness, such as Arkema SA of Colombes, France. 7233SA 01MED resin, while the proximal segment (530p) and / or the middle segment (530m) may include a second polyether block amide (PEBA) having a second hardness less than the first hardness. In this regard, the cannula (530) can be manufactured via a two-shot injection molding process, such as where the distal segment (530d) and / or the distal end (532) are formed via a first injection molding process, and / or the proximal segment (530p) and / or the middle segment (530m) are formed via a second injection molding process. As described above, the relatively high stiffness of the distal segment (530d) can reduce any curvature that may be imparted to the cannula (530) by a needle (such as needle (150)) that is retracted into the cannula (530), and thereby facilitate atraumatic passage of the cannula (530) along the suprachoroidal space when the needle (150) is retracted therein.

[0107] In the present example, the substantially rectangular, substantially elliptical, or other substantially flat cross-sectional profile of the distal segment (530d) of cannula (530) prevents cannula (530) from rotating about the longitudinal axis of cannula (530) when cannula (530) is disposed in the suprachoroidal space.

[0108] In other words, as the needle (550, 650, 750, 850, 950, 1050, 1150) advances distally from the cannula (530), the cross-sectional profile of the distal segment (530d) of the cannula (530) can assist in maintaining the orientation of the side recess (536) toward the internal region of the eye (301), thereby facilitating proper trajectory of the needle (550, 650, 750, 850, 950, 1050, 1150) toward the internal region of the eye (301). Thus, the combination of the wedge shape of the distal end portion (532) and the cross-sectional profile of the distal segment (530d) can 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) is advanced distally relative to the cannula (530). The cross-sectional profiles of the proximal segment (530p) and / or the middle segment (530m) can provide a similar effect.

[0109] In the example shown, the needle guide (541) is disposed within the needle guide lumen (539) of the cannula (530). The needle guide (541) can be fixed within the needle guide lumen (539) of the cannula (530) by a press fit or an interference fit, by an adhesive, by a mechanical locking mechanism, and / or in any other suitable manner. In some cases, the cannula (530) can be overmolded onto the needle guide (541), such as via the two injection molding process described above. In the present example, the needle guide (541) is formed of a polyimide material, but it should be understood that one or more other suitable biocompatible materials can be used, such as one or more other suitable biocompatible materials having a hardness less than that of stainless steel. The needle guide (541) of the present example is substantially straight, but can be bent with the cannula (530). 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 described above, the relatively low durometer of the material of needle guide (541) can improve the ability of cannula (530) to conform to the specific structure and contours of eye (301).

[0110] In the example shown, the proximal support tube (544) is at least partially disposed within a 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) can be disposed within the proximal support tube (544) so ​​that the proximal portion of the needle guide (541) can be radially interposed between the needle (150, 550, 650, 750, 850, 950, 1050, 1150) and the support tube (544). The support tube (544) can be fixed within the needle guide lumen (539) of the cannula (530) by a press fit or an interference fit, by an adhesive, by a mechanical locking mechanism, and / or in any other suitable manner. In some cases, the cannula (530) can be overmolded onto the support tube (544), such as via the two-shot molding process described above. In the present example, support tube (544) is formed of a polyimide material, but it should be understood that one or more other suitable biocompatible materials may be used, such as one or more other suitable biocompatible materials having a hardness less than that of stainless steel. Thus, support tube (544) may be constructed similarly to needle guide (541), but support tube (544) may have a wall thickness greater than the wall thickness of needle guide (541) and / or an external cross-sectional dimension (e.g., diameter) greater than the external cross-sectional dimension of needle guide, such that support tube (544) may have a greater rigidity than the rigidity of needle guide (541). As shown, support tube (544) extends proximally from cannula (530) a sixth distance (D6). By way of example only, the sixth distance (D6) may be approximately 6.5 mm. The relatively high stiffness of the support tube (544) may allow the support tube (544) to support the needle (150, 550, 650, 750, 850, 950, 1050, 1150) in a region of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) proximal to the cannula (530), thereby inhibiting kinking of the needle (150, 550, 650, 750, 850, 950, 1050, 1150) in the region proximal to the cannula (530).It should be understood that the support tube (544) can directly support the needle (150, 550, 650, 750, 850, 950, 1050, 1150), such as when the needle guide (541) is not radially inserted between the needle (150, 550, 650, 750, 850, 950, 1050, 1150) and the support tube (544); and / or can indirectly support the needle (150, 550, 650, 750, 850, 950, 1050, 1150), such as via the proximal portion of the needle guide (541) when the proximal portion of the needle guide (541) is radially inserted between the needle (150, 550, 650, 750, 850, 950, 1050, 1150) and the support tube (544).

[0111] In the example shown, the cannula (530) may include a plurality of markings (546a, 546b) on the surface of the cannula (530) to indicate various insertion depths. The markings (546a, 546b) may be positioned to assist an operator in identifying the correct insertion depth as the cannula (530) is guided along an atraumatic path. For example, an operator may visually observe the position of the markings (546a, 546b) 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) has been inserted into the eye (301). In the example shown, the first marking (546a) is spaced proximally from the tip of the distal end (532) by a seventh distance (D7), such that the first marking (546a) can correspond to an insertion depth of the cannula (530) approximately equal to the seventh distance (D7); and the second marking (546b) is spaced proximally from the tip of the distal end (532) by an eighth distance (D8), such that the second marking (546b) can correspond to an insertion depth of the cannula (530) approximately equal to the eighth distance (D8). Although not shown, the third marking can be spaced proximally from the tip of the distal end (532) by a ninth distance, such that the third marking can correspond to an insertion depth of the cannula (530) approximately equal to the ninth distance; and the fourth marking can be spaced proximally from the tip of the distal end (532) by a tenth distance, such that the fourth marking can correspond 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 may be about 5 mm; the eighth distance (D8) may range from about 9.5 mm to about 10.5 mm, or more specifically may be about 10 mm; the ninth distance may range from about 14.5 mm to about 15.5 mm, or more specifically may be about 15 mm; and / or the tenth distance may range from about 19.5 mm to about 20.5 mm, or more specifically may be about 20 mm. It should be appreciated that any suitable number of markings (546a, 546b) may be positioned on the surface of the cannula (530) and may be spaced any suitable distance proximally from the tip of the distal end (532) to indicate a corresponding insertion depth.

[0113] IV. Examples of Alternative Needles for Instruments

[0114] In some cases, it may be desirable to provide the needle (150) with one or more preformed curved portions so that when the needle (150) is slidably disposed in the cannula (130), the needle (150) can impart at least some degree of curvature to the cannula. Such a curved portion can improve the ability of the needle (150) to enter the subretinal space of an eye (301) that is relatively small (e.g., about 16 mm in diameter, otherwise less than about 24 mm in diameter), at least as compared to an eye (301) of an adult patient (e.g., an eye of a pediatric human patient, or an eye of a non-human patient such as a canine patient or a non-human primate patient). Such a curved portion of the needle (150) can improve the ability of the needle (150) and / or cannula (130) to conform to the specific structure and contours of the eye (301). Additionally or alternatively, such a curved portion can inhibit unintended movement of the distal tip (152) of the needle (150) that might otherwise be caused by movement of the body (110) of the instrument (100). It should be understood that by inhibiting such unintended movement of the distal tip (152), such a curved portion can assist in maintaining the distal tip (152) along a predetermined trajectory and at an angle in a predetermined orientation while within the eye (301), thereby improving the ability of the needle (150) to enter the subretinal space of the eye (301).

[0115] Various illustrative examples of such needles (550, 650, 750, 850, 950, 1050, 1150) are described in greater detail below. Although needles (550, 650, 750, 850, 950, 1050, 1150) are described below in conjunction with cannula (130), it should 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) may be readily incorporated into instrument (100) in place of needle (150), and any of cannulas (430, 530) may be readily incorporated into instrument (100) in place of cannula (130). Although the examples described above are provided in the context of a relatively small eye (301), the teachings below may also be employed in the context of an adult patient's eye (301), such that the teachings below are not limited to the context of a relatively small eye (301).

[0116] A. First Example of a Needle with Proximal and Distal Curves

[0117] Figure 23 to Figure 24 An example of a needle (550) is shown, which can be easily incorporated into the instrument (100) in place of the needle (150). The needle (550) can be similar to the needle (150) described above, unless otherwise described below. In this regard, the needle (550) of this example has a sharp distal tip (552) and defines a lumen (not shown). The distal tip (552) of this example has a single bevel configuration. In some other versions, the distal tip (552) has a three-bevel configuration or any other suitable configuration, such as any of the configurations described in U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. In view of the teachings herein, other other suitable forms that the distal tip (552) can take will be apparent to those skilled in the art. In this example, the needle (550) is formed of nitinol, but it should be understood that one or more other suitable materials (e.g., stainless steel, etc.) may be used.

[0118] Needle (550) of the present example includes a substantially straight proximal portion (560), a substantially curved proximal portion (562), a substantially straight middle portion (564), a substantially curved distal portion (566), and a substantially straight distal portion (568). The proximal curved portion (562) is longitudinally interposed between the proximal straight portion (560) and the middle straight portion (564); the middle straight portion (564) is longitudinally interposed between the proximal curved portion (562) and the distal curved portion (566); the distal curved portion (566) is longitudinally interposed between the middle straight portion (564) and the distal straight portion (568); and the distal straight portion (568) is longitudinally interposed between the distal curved portion (566) and the distal tip (552). In the example shown, the proximal curved portion (562) and the distal curved portion (566) curve in opposite directions from each other to provide the needle (550) with a generally S-shaped configuration. Figure 23 to Figure 24 Within the reference frame of , the proximal curved portion ( 562 ) curves generally clockwise in the distal direction, while the distal curved portion ( 566 ) curves generally counterclockwise in the distal direction.

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

[0120] It should be understood that a portion of needle (550) may be “positioned within eye (301) during use” even if that portion of needle (550) remains within cannula (130, 430, 530) as long as a corresponding portion of cannula (130, 430, 530) is positioned within eye (301). Thus, in order for a portion of needle (550) to be “positioned within eye (301) during use”, it is not necessary that that portion of needle (550) be exposed distally relative to cannula (130, 430, 530).

[0121] The needle (550) is configured to provide a proximal bend (562) and a distal bend (566) as preformed features such that the needle (550) is resiliently biased to present a Fig.23 In the example shown, 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 at a proximal end distance (X1) from the needle (550) along a first (e.g., horizontal) axis and a proximal end distance (Y1) from 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 may be about 14.4 mm; the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically may be about 18 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the distance (X1) may range from about 11.52 mm to about 17.28 mm, or more specifically may be about 14.4 mm; the distance (Y1) may range from about 14.36 mm to about 21.6 mm, or more specifically may be about 18 mm. m to about 21.54mm, or more specifically can be about 17.95mm; the length (L2) can range from about 32mm to about 48mm, or more specifically can be about 40mm; the radius of curvature (R2) can range from about 2.8mm to about 4.2mm, or more specifically can be about 3.5mm; the arc length (S2) can range from about 3.36mm to about 5.04mm, or more specifically can be about 4.2mm; and / or the length (L3) can range from about 0.56mm to about 0.84mm, or more specifically can be about 0.7mm.

[0123] The proximal straight portion (560) can be configured to extend proximally away from the eye (301) and toward the body (110) of the device (100), while the intermediate straight portion (564), the distal curved portion (566), and / or the distal straight portion (568) are disposed within the eye (301). In this regard, while the intermediate straight portion (564) and the portion of the cannula (130, 430, 530) in which the intermediate straight portion (564) is disposed can conform to the curvature of the eye (301), the proximal curved portion (562) can bend in the opposite direction and can impart at least some degree of curvature to the cannula (130, 430, 530) such that the portion of the cannula (130, 430, 530) outside of the eye (301) can likewise bend in the opposite direction. For example, in FIG. 7C to FIG. 7G Any one or more of the stages shown in FIG. 7C to FIG. 7G Within the reference frame of , the proximal bend portion (562) can cause the portion of the cannula (130, 430, 530) outside the eye (301) to bend generally clockwise in a proximal direction away from the eye (301) and toward the body (110).

[0124] Such curvature of the cannula (130, 430, 530) induced by the proximal curved portion (562) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (552); and can thereby inhibit unintended movement of the distal tip (552) that might otherwise be caused by 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 can effectively absorb some or all of such movement, rather than 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 curvature of cannula (130, 430, 530) induced by proximal curved portion (562) may further assist the portion of cannula (130, 430, 530) within eye (301) in conforming to the curvature of eye (301).

[0125] While needle (550) of the present example includes a single proximal curve (562) having a constant radius of curvature (R1), in some other versions, the radius of curvature (R1) may be variable and / or more than one proximal curve (562) may be provided, such as described in more detail below.

[0126] The distal bend (566) can be configured to orient the distal tip (552) along one or more predetermined exit axes during distal advancement of the needle (550) relative to the cannula (130, 430, 530) to protrude from the opening (134). For example, the distal bend (566) can be configured and operative in accordance with at least some 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 Needle with Proximal and Distal Curves

[0128] Figure 25 to Figure 26 Another example of a needle (650) is shown that can be easily incorporated into device (100) in place of needle (150). Needle (650) can be similar to needle (550) described above, except as otherwise described below. In this regard, needle (650) of the present example has a sharp distal tip (652) and defines a lumen (not shown).

[0129] Needle (650) of the present example includes a substantially straight proximal portion (660), a substantially curved proximal portion (662), a substantially straight middle portion (664), a substantially curved distal portion (666), and a substantially straight distal portion (668). In the example shown, proximal curved portion (662) and distal curved portion (666) curve in opposite directions from each other to provide needle (650) with a generally S-shaped configuration. For example, in Figure 25 to Figure 26 Within the reference frame of , the proximal curved portion ( 662 ) curves generally clockwise in the distal direction, while the distal curved portion ( 666 ) curves generally counterclockwise in the distal direction.

[0130] Needle (650) is configured to provide a proximal bend (662) and a distal bend (666) as preformed features such that needle (650) is resiliently biased to present a Fig.25 In the example shown, the proximal straight portion (660) has a length (L1); the proximal curved portion (662) has a constant radius of curvature (R1) and an arc length (S1); the intermediate straight portion (664) has a length (L2); the distal curved portion (666) has a constant radius of curvature (R2) and an arc length (S2); and the 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 may be about 14.4 mm; the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the arc length (S1) may range from about 24 mm to about 36 mm, or more specifically may be about 30 mm; the length (L2) may range from about 24 mm to about 36 mm, or more specifically may be about 30 mm; the radius of curvature (R2) may range from about 2.8 mm to about 4.2 mm, or more specifically may be about 3.5 mm; the arc length (S2) may range from about 3.36 mm to about 5.04 mm, or more specifically may be about 4.2 mm; and / or the length (L3) may range from about 0.56 mm to about 0.84 mm, or more specifically may be about 0.7 mm.

[0132] In some versions, the proximal curved portion (662) may be configured similarly to the above combined Fig.23 The described manner allows the portion of the cannula (130, 430, 530) outside the eye (301) to bend away from the eye (301) and toward the body (110). Such curvature of the cannula (130, 430, 530) induced by the proximal curved portion (662) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (652); and can thereby inhibit unintended movement of the distal tip (652) that might otherwise be caused by 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 can effectively absorb some or all of such movement, rather than 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 curvature of cannula (130, 430, 530) induced by proximal curved portion (662) may further assist in conforming the portion of cannula (130, 430, 530) within eye (301) to the curvature of eye (301).

[0133] C. Third Example of Needle with Proximal and Distal Curves

[0134] Figure 27 to Figure 28 Another example of a needle (750) is shown that can be easily incorporated into device (100) in place of needle (150). Needle (750) can be similar to needle (550) described above, except as otherwise described below. In this regard, needle (750) of the present example has a sharp distal tip (752) and defines a lumen (not shown).

[0135] Needle (750) of the present example includes a substantially straight proximal portion (760), a substantially curved proximal portion (762), a substantially straight middle portion (764), a substantially curved distal portion (766), and a substantially straight distal portion (768). In the example shown, proximal curved portion (762) and distal curved portion (766) curve in opposite directions from each other to provide needle (750) with a generally S-shaped configuration. For example, in Figure 27 to Figure 28 Within the reference frame of , the proximal curved portion ( 762 ) curves generally clockwise in the distal direction, while the distal curved portion ( 766 ) curves generally counterclockwise in the distal direction.

[0136] Needle (750) is configured to provide a proximal bend (762) and a distal bend (766) as preformed features such that needle (750) is resiliently biased to present a Fig. 27 In the example shown, the proximal straight portion (760) has a length (L1); the proximal curved portion (762) has a constant radius of curvature (R1) and an arc length (S1); the intermediate straight portion (764) has a length (L2); the distal curved portion (766) has a constant radius of curvature (R2) and an arc length (S2); and the distal straight portion (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 may be about 14.4 mm; the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the length (L2) may range from about 32 mm to about 48 mm, or more specifically may be about 40 mm; the radius of curvature (R2) may range from about 2.8 mm to about 4.2 mm, or more specifically may be about 3.5 mm; the arc length (S2) may range from about 3.36 mm to about 5.04 mm, or more specifically may be about 4.2 mm; and / or the length (L3) may range from about 0.56 mm to about 0.84 mm, or more specifically may be about 0.7 mm.

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

[0139] In some versions, proximal curved portion (762) may be configured similarly to the above combined Fig.23 The described manner allows the portion of the cannula (130, 430, 530) outside the eye (301) to bend away from the eye (301) and toward the body (110). Such curvature of the cannula (130, 430, 530) induced by the proximal curved portion (762) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (752); and can thereby inhibit unintended movement of the distal tip (752) that might otherwise be caused by 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 can effectively absorb some or all of such movement, rather than 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 curvature of cannula (130, 430, 530) induced by proximal curved portion (762) may further assist in conforming the portion of cannula (130, 430, 530) within eye (301) to the curvature of eye (301).

[0140] D. Example of a Needle Having a First Proximal Curve and a Second Proximal Curve and a Distal Curve

[0141] Figure 29 to Figure 32Another example of a needle (850) is shown that can be easily incorporated into device (100) in place of needle (150). Needle (850) can be similar to needle (550) described above, except as otherwise described below. In this regard, needle (850) of the present example has a sharp distal tip (852) and defines a lumen (not shown).

[0142] The needle (850) of the present 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 middle 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 example shown, the proximal curved portions (862, 863) and the distal curved portion (866) are bent in opposite directions to each other to provide the needle (850) with a generally S-shaped configuration. For example, in Figure 29 to Figure 32 Within the reference frame of , the proximal curved portions ( 862 , 863 ) are each curved generally clockwise in the distal direction, while the distal curved portion ( 866 ) is curved generally counterclockwise in the distal direction.

[0143] The needle (850) is configured to provide proximal bends (862, 863) and distal bends (866) as preformed features such that the needle (850) is resiliently biased to present a Fig.29 and Figure 31 to Figure 32In the example shown, the proximal straight portion (860) has a length (L1); the first proximal curved portion (862) has a constant radius of curvature (R1), arc length (S1), and center of curvature (C1) and is defined by a reference circle having a center (C1) and a first diameter (D1), the center of curvature being located at a proximal end distance (X1) from the needle (850) along a first (e.g., horizontal) axis and at a proximal end distance (Y1) from the needle (850) along a second (e.g., vertical) axis; the second proximal curved portion (863) has a constant radius of curvature ( R2), arc length (S2) and center of curvature (C2) and is defined by a reference circle having a center (C2) and a second diameter (D2), the center of curvature being located at a proximal end distance (X2) from the needle (850) along a first (e.g., horizontal) axis and at a proximal end distance (Y2) from the needle (850) along a second (e.g., vertical) axis; the middle straight portion (864) having a length (L2); the distal curved portion (866) having a constant radius of curvature (R3) and arc length (S3); and the distal straight portion (868) having 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 may be about 14.4 mm; the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically may be about 18 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the distance (X1) may range from about 11.52 mm to about 17.28 mm, or more specifically may be about 14.4 mm; the distance (Y1) may range from about 14.4 mm to about 21.6 mm, or more specifically may be about 18 mm; the diameter (D1) may range from about 28.8 mm to about 43.2, or more specifically may be about 36 mm; the radius of curvature (R2) may range from about 10 mm to about 15 mm, or more specifically may be about 12.5 mm; the arc length (S2) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; about 24mm, or more specifically about 20mm; the distance (X2) can range from about 15.46mm to about 23.2mm, or more specifically about 19.33mm; the distance (Y1) can range from about 12.45mm to about 18.67mm, or more specifically about 15.56mm; the diameter (D2) can range from about 20mm to about 30mm, or more specifically about 25mm; the length (L2) can range from about 16mm to about 24mm, or more specifically about 20mm; the radius of curvature (R3) can range from about 2.8mm to about 4.2mm, or more specifically about 3.5mm; the arc length (S3) can range from about 3.36mm to about 5.04mm, or more specifically about 4.2mm; and / or the length (L3) can range from about 0.56mm to about 0.84mm, or more specifically about 0.7mm.

[0145] In some versions, one or both proximal curved portions (862, 863) may be configured similarly to the above combined Fig.23The described manner causes the portion of the cannula (130, 430, 530) outside the eye (301) to bend away from the eye (301) and toward the body (110). Such curvature of the cannula (130, 430, 530) induced by one or both proximal curved portions (862, 863) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (852); and thereby can inhibit unintended movement of the distal tip (852) that might otherwise be caused by movement of the body (110). For example, one or two proximal curved portions (862, 863) and / or the portion of the cannula (130, 430, 530) in which one or two proximal curved portions (862, 863) are disposed can effectively absorb some or all of such movement, rather than transmitting such movement distally to the intermediate straight portion (864), distal curved portion (866), and distal straight portion (868) of the needle (850). Additionally or alternatively, the curvature of the cannula (130, 430, 530) induced by one or two proximal curved portions (862, 863) can further assist the portion of the cannula (130, 430, 530) within the eye (301) to conform to the curvature of the eye (301).

[0146] E. Example of a Needle Having a First Distal Curve and a Second Distal Curve

[0147] Figure 33 to Figure 35 Another example of a needle (950) is shown, which can be easily incorporated into the instrument (100) in place of the needle (150). The needle (950) can be similar to the needle (150) described above, unless otherwise described below. In this regard, the needle (950) of this example has a sharp distal tip (952) and defines a lumen (not shown). The distal tip (952) of this example has a single bevel configuration. In some other versions, the distal tip (952) has a three-bevel configuration or any other suitable configuration, such as any of the configurations described in U.S. Patent No. 10,226,379, the disclosure of which is incorporated herein by reference in its entirety. In view of the teachings herein, other other suitable forms that the distal tip (952) can take will be apparent to those skilled in the art. In this example, the needle (950) is formed of nitinol, but it should be understood that one or more other suitable materials (e.g., stainless steel, etc.) may be used.

[0148] The needle (950) of the present 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 example shown, the distal curved portions (965, 966) are curved in the same direction as one another to provide the needle (950) with a generally J-shaped configuration. For example, in Figure 33 to Figure 35 Within the reference frame of , the distal curved portions (965, 966) are each curved generally counterclockwise in the distal direction.

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

[0150] The needle (950) is configured to provide distal curved portions (965, 966) as preformed features such that the needle (950) is resiliently biased to present a Fig.33 and Fig.35 In the example shown, the proximal straight portion (960) has a length (L1); the first distal curved portion (965) has a constant radius of curvature (R1), arc length (S1), and center of curvature (C1) and is defined by a reference circle having a center (C1) and a diameter (D1), the center of curvature being located at a proximal end distance (X1) from the needle (950) along a first (e.g., horizontal) axis and at a proximal end distance (Y1) from the needle (950) along a second (e.g., vertical) axis; the second distal curved portion (966) has a constant radius of curvature (R2) and 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 may be about 54.4 mm; the radius of curvature (R1) may range from about 10 mm to about 15 mm, or more specifically may be about 12.5 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the distance (X1) may range from about 43.52 mm to about 65.28 mm, or more specifically may be about 54.4 mm; the distance (Y1) may range from about 9.94 mm to about 11.8 mm; the distance (X2) may range from about 43.52 mm to about 65.28 mm, or more specifically may be about 54.4 mm; the distance (Y3) may range from about 9.94 mm to about 13.8 mm; the distance (Y4) may range from about 11.8 mm to about 13.8 mm; the distance (Y5) may range from about 11.8 mm to about 15.8 mm; the distance (S6) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm. mm to about 14.9 mm, or more specifically about 12.42 mm; D1 can range from about 20 mm to about 30 mm, or more specifically about 25 mm; the radius of curvature (R2) can range from about 2.8 mm to about 4.2 mm, or more specifically about 3.5 mm; the arc length (S2) can range from about 3.36 mm to about 5.04 mm, or more specifically about 4.2 mm; and / or the length (L2) can range from about 0.56 mm to about 0.84 mm, or more specifically about 0.7 mm.

[0152] In some versions, first distal curved portion (965) may impart at least some degree of curvature to cannula (130, 430, 530), such as at FIG. 7C to FIG. 7G , 965). Such curvature of the cannula (130, 430, 530) induced by the first distal curved portion (965) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (952); and can thereby inhibit unintended movement of the distal tip (952) that might otherwise be caused by 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 can effectively absorb some or all of such movement, rather than transmitting such movement distally to the second distal curved portion (966) and the distal straight portion (968) of the needle (950). Additionally or alternatively, the curvature of the cannula (130, 430, 530) induced by the first distal curved portion (965) may further assist in conforming the portion of the cannula (130, 430, 530) within the eye (301) to the curvature of the eye (301).

[0153] The second distal curved portion (966) can 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) can be configured and operative in accordance with at least some of the teachings of U.S. Pat. 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 a First Distal Curve and a Second Distal Curve

[0155] Figure 36 to Figure 37 Another example of a needle (1050) is shown that can be easily incorporated into device (100) in place of needle (150). Needle (1050) can be similar to needle (550) and / or needle (950) described above, except as otherwise described below. In this regard, needle (1050) of the present example has a sharp distal tip (1052) and defines a lumen (not shown).

[0156] The needle (1050) of the present example includes a substantially straight proximal portion (1060), a substantially curved proximal portion (1062), a substantially straight middle 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 inserted between the proximal straight portion (1060) and the intermediate straight portion (1064); the intermediate straight portion (1064) is longitudinally inserted between the proximal curved portion (1062) and the first distal curved portion (1065); the first distal curved portion (1065) is longitudinally inserted between the intermediate straight portion (1064) and the second distal curved portion (1066); the second distal curved portion (1066) is longitudinally inserted between the first distal curved portion (1065) and the distal straight portion (1068); and the distal straight portion (1068) is longitudinally inserted between the second distal curved portion (1066) and the distal tip (1052). In the example shown, the proximal curved portion (1062) and the distal curved portions (1065, 1066) curve in opposite directions from one another to provide the needle (1050) with a generally S-shaped configuration. Figure 36 to Figure 37 Within the reference frame of , the proximal curved portion (1062) curves generally clockwise in the distal direction, while the distal curved portions (1065, 1066) each curve generally counterclockwise in the distal direction.

[0157] The needle (1050) is configured to provide a proximal bend (1062) and a distal bend (1065, 1066) as preformed features such that the needle (1050) is resiliently biased to present a Fig.36 In the example shown, 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 may be about 24.9 mm; the radius of curvature (R1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the length (L2) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the radius of curvature (R2) may range from about 13.6 mm to about 16 mm; about 20.4mm, or more specifically about 17mm; the arc length (S2) can range from about 8mm to about 12mm, or more specifically about 10mm; the radius of curvature (R3) can range from about 2.8mm to about 4.2mm, or more specifically about 3.5mm; the arc length (S3) can range from about 3.36mm to about 5.04mm, or more specifically about 4.2mm; and / or the length (L3) can range from about 0.56mm to about 0.84mm, or more specifically about 0.7mm.

[0159] In some versions, the intermediate straight portion (1064) can be omitted such that the proximal curved portion (1062) can directly interface with the first distal curved portion (1065). Additionally or alternatively, the proximal straight portion (1060) can have a slight curvature such that the proximal straight portion (1060) can have an arc length (S0). In some versions, the arc lengths (S0, S1, S2, S3) of the proximal straight portion (1060), the proximal curved portion (1062), the first distal curved portion (1065), and the second distal curved portion (1066) can be selected from the following table, where all values ​​are approximate.

[0160] S3 S2 S1 S0 2mm 18mm 20mm 5mm 3mm 8mm 12mm 0mm 1.5mm 8mm 12mm 0mm 3mm 8mm 12mm 0mm 1.5mm 8mm 12mm 0mm 1.5mm 8mm 12mm 0mm

[0161] In some versions, proximal curved portion (1062) may be configured similarly to the above combined Fig.23 The described manner causes the portion of the cannula (130, 430, 530) outside the eye (301) to bend away from the eye (301) and toward the body (110). Such curvature of the cannula (130, 430, 530) induced by the proximal curved portion (1062) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (1052); and thereby can inhibit unintended movement of the distal tip (1052) that might otherwise be caused by 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 can effectively absorb some or all of such movement, rather than 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 curvature of the cannula (130, 430, 530) induced by the proximal curved portion (1062) can further assist the portion of the cannula (130, 430, 530) within the eye (301) to conform to the curvature of the eye (301).

[0162] G. Example of a Needle Having First and Second Proximal Curves and First and Second Distal Curves

[0163] Figure 38 to Figure 39 Another example of a needle (1150) is shown that can be easily incorporated into device (100) in place of needle (150). Needle (1150) can be similar to needle (550) and / or needle (950) described above, except as otherwise described below. In this regard, needle (1150) of the present example has a sharp distal tip (1152) and defines a lumen (not shown).

[0164] The needle (1150) of the present 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 inserted between the proximal straight portion (1160) and the second proximal curved portion (1163); the second proximal curved portion (1163) is longitudinally inserted between the first proximal curved portion (1162) and the first distal curved portion (1165); the first distal curved portion (1165) is longitudinally inserted between the second proximal curved portion (1163) and the second distal curved portion (1166); the second distal curved portion (1166) is longitudinally inserted between the first distal curved portion (1165) and the distal straight portion (1168); and the distal straight portion (1168) is longitudinally inserted between the second distal curved portion (1166) and the distal tip (1152). In some versions, needle (1150) may include a substantially straight intermediate portion (not shown), for example, interposed longitudinally between second proximal curved portion (1163) and first distal curved portion (1165). In the example shown, proximal curved portions (1162, 1163) and distal curved portions (1165, 1166) curve in opposite directions from one another to provide needle (1150) with a generally S-shaped configuration. For example, in Figure 38 to Figure 39 Within the reference system of , the proximal curved portions (1162, 1163) are each curved generally clockwise in the distal direction, while the distal curved portions (1165, 1066) are each curved generally counterclockwise in the distal direction.

[0165] The needle (1150) is configured to provide proximal bends (1162, 1163) and distal bends (1165, 1166) as preformed features such that the needle (1150) is resiliently biased to present a Fig.38 In the example shown, 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).

[0166] By way of example only, the length (L1) may range from about 12.08 mm to about 18.12 mm, or more specifically may be about 15.1 mm; the radius of curvature (R1) may range from about 14.4 mm to about 21.6 mm, or more specifically may be about 18 mm; the arc length (S1) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm; the radius of curvature (R2) may range from about 10 mm to about 15 mm, or more specifically may be about 12.5 mm; the arc length (S2) may range from about 16 mm to about 24 mm, or more specifically may be about 20 mm ; the radius of curvature (R3) can range from about 10 mm to about 15 mm, or more specifically can be about 12.5 mm; the arc length (S3) can range from about 16 mm to about 24 mm, or more specifically can be about 20 mm; the radius of curvature (R4) can range from about 2.8 mm to about 4.2 mm, or more specifically can be about 3.5 mm; the arc length (S4) can range from about 3.36 mm to about 5.04 mm, or more specifically can be about 4.2 mm; and / or the length (L2) can range from about 0.56 mm to about 0.84 mm, or more specifically can be about 0.7 mm.

[0167] In some versions, one or both proximal curved portions (1162, 1163) may be configured similarly to the above combined Fig.23 The described manner causes the portion of the cannula (130, 430, 530) outside the eye (301) to bend away from the eye (301) and toward the body (110). Such curvature of the cannula (130, 430, 530) induced by one or both proximal curved portions (1162, 1163) can limit the effect of any movement of the body (110) of the instrument (100) on the position of the distal tip (1152); and thereby can inhibit unintended movement of the distal tip (1152) that might otherwise be caused by movement of the body (110). For example, one or two proximal curved portions (1162, 1163) and / or the portion of the cannula (130, 430, 530) in which one or two proximal curved portions (1162, 1163) are disposed can effectively absorb some or all of such movement, rather than 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 curvature of the cannula (130, 430, 530) induced by one or two proximal curved portions (1162, 1163) can further assist the portion of the cannula (130, 430, 530) within the eye (301) to conform to the curvature of the eye (301).

[0168] V. Exemplary Combinations

[0169] The following examples relate to various non-exhaustive ways in which the teachings of this article may be combined or applied. It should be understood that the following examples are not intended to limit the coverage of any claims that may be filed at any time in this application or in subsequent filings of this application. No disclaimer is intended. The following examples are provided for illustrative purposes only. It is contemplated that the various teachings of this article may be arranged and applied in a variety of other ways. It is also contemplated that some variations may omit certain features mentioned in the following examples. Therefore, any aspect or feature mentioned below should not be considered critical unless otherwise explicitly indicated by the inventor or the inventor's successor at a later date. If any claim filed in this application or a subsequent application related to this application includes additional features beyond those mentioned below, it should not be presumed that these additional features are added for any reason related to patentability.

[0170] Example 1

[0171] A device comprising: (a) a body; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of a patient's eye; and (c) a needle slidably disposed in the cannula, wherein the needle comprises: (i) a sharp distal tip, wherein the needle is configured to translate between a proximal position and a distal position relative to the cannula, wherein the distal tip is configured to be positioned inside the cannula when the needle is in the proximal position, wherein the distal tip is configured to be positioned outside the cannula when the needle is in the distal position, (ii) at least one proximal curve, wherein the needle is resiliently biased to extend through the at least one proximal curve along at least one proximal curve, and (iii) at least one distal curve, wherein the needle is resiliently biased to extend through the at least one distal curve along at least one distal curve, wherein the at least one distal curve is different from the at least one proximal curve.

[0172] Example 2

[0173] A device according to Example 1, wherein the needle further includes a distal straight portion extending along the outlet axis, wherein the distal straight portion is longitudinally inserted between the at least one distal curved portion and the sharp distal tip, and wherein the needle is elastically biased to extend along a straight path along the distal straight portion.

[0174] Example 3

[0175] A device according to any of Examples 1 to 2, wherein the needle further includes a proximal straight portion, wherein the at least one proximal curved portion is longitudinally inserted between the proximal straight portion and the at least one distal curved portion, and wherein the needle is elastically biased to extend along a straight path along the proximal straight portion.

[0176] Example 4

[0177] A device according to any of Examples 1 to 3, wherein the needle further includes an intermediate straight portion, wherein the intermediate straight portion is longitudinally inserted between the at least one proximal curved portion and the at least one distal curved portion, wherein the needle is elastically biased to extend along a straight path along the intermediate straight portion.

[0178] Example 5

[0179] A device according to any one of Examples 1 to 4, wherein the at least one proximal curve portion includes a first proximal curve portion and a second proximal curve portion, wherein the needle is elastically biased to extend through the first proximal curve portion and the second proximal curve portion along the first proximal curve and the second proximal curve, respectively.

[0180] Example 6

[0181] A device according to any one of Examples 1 to 5, wherein the at least one distal curve portion includes a first distal curve portion and a second distal curve portion, wherein the needle is elastically biased to extend through the first distal curve portion and the second distal curve portion along the first distal curve and the second distal curve, respectively.

[0182] Example 7

[0183] A device according to any one of Examples 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.

[0184] Example 8

[0185] A device according to any of Examples 1 to 7, wherein the needle is resiliently biased to define an "S" shape.

[0186] Example 9

[0187] A device according to any of Examples 1 to 8, wherein the at least one proximal bend is configured to be positioned within the cannula when the needle is in the distal position.

[0188] Example 10

[0189] A device according to any of Examples 1 to 9, wherein the at least one proximal bend is configured to be positioned outside of the patient's eye when the needle is in the distal position.

[0190] Example 11

[0191] A device according to any of Examples 1 to 10, wherein the at least one proximal bend is configured to inhibit movement of the body from being transmitted to the distal tip.

[0192] Example 12

[0193] The device of any of Examples 1-11, wherein the at least one proximal bend is configured to impart a curvature to the cannula.

[0194] Example 13

[0195] The device of any of Examples 1-12, wherein the needle comprises nitinol.

[0196] Example 14

[0197] A device according to any of Examples 1 to 13, wherein the distal tip is beveled.

[0198] Example 15

[0199] A device according to any of Examples 1 to 14, wherein the cannula is flexible enough to conform to the structure and contour of the patient's eye, yet the cannula also has sufficient column strength to allow the cannula to pass between the sclera and the choroid of the patient's eye without buckling.

[0200] Example 16

[0201] The device according to any one of Examples 1 to 15 further includes: (a) a needle guide, which is disposed between the needle and the cannula; and (b) a support tube, which is partially disposed in the cannula proximal to the needle guide, wherein the support tube extends proximally from the cannula, wherein the support tube is more rigid than the needle guide.

[0202] Example 17

[0203] The device according to Example 16, wherein the support tube and the needle guide comprise the same material as each other.

[0204] Example 18

[0205] The device of any of Examples 1-17, wherein the cannula comprises a proximal segment comprising a first material, and a distal segment comprising a second material different from the first material.

[0206] Example 19

[0207] The device of any of Examples 1-18, wherein the at least one proximal curve has an arc length ranging from about 16 mm to about 24 mm.

[0208] Example 20

[0209] The device of any of Examples 1-19, wherein the at least one proximal curve has a radius of curvature ranging from approximately 16 mm to approximately 24 mm.

[0210] Example 21

[0211] The device of any of Examples 1-20, wherein the at least one distal curve has an arc length ranging from approximately 2.8 mm to approximately 4.2 mm.

[0212] Example 22

[0213] The device of any of Examples 1-21, wherein the at least one distal curve has a radius of curvature ranging from about 2 mm to about 3 mm.

[0214] Example 23

[0215] A device according to any of Examples 2 to 22, wherein the distal straight portion has a length ranging from approximately 0.56 mm to approximately 0.84 mm.

[0216] Example 24

[0217] A device according to any of Examples 3 to 23, wherein the proximal straight portion has a length ranging from about 20 mm to about 30 mm.

[0218] Example 25

[0219] The device of any of Examples 4-24, wherein the intermediate straight portion has a length ranging from approximately 36.64 mm to approximately 54.96 mm.

[0220] Example 26

[0221] A device comprising: (a) a body; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of a patient's eye; and (c) a needle slidably disposed in the cannula, wherein the needle comprises: (i) a sharp distal tip, wherein the needle is configured to translate between a proximal position and a distal position relative to the cannula, wherein the distal tip is configured to be positioned inside the cannula when the needle is in the proximal position, and wherein the distal tip is configured to be positioned outside the cannula when the needle is in the distal position; (ii) a first curved portion, wherein the needle is elastically biased to extend through the first curved portion along a first curve; and (iii) a second curved portion longitudinally spaced apart from the first curved portion, wherein the needle is elastically biased to extend through the second curved portion along a second curve.

[0222] Example 27

[0223] A device comprising: (a) a body; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of an eye of a patient; wherein the cannula comprises: (i) a proximal segment having a first cross-sectional area, (ii) a middle 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 in the cannula

[0224] Example 28

[0225] A device according to Example 27, wherein the second cross-sectional area is smaller than the first cross-sectional area.

[0226] Example 29

[0227] A device according to any of Examples 27 to 28, wherein the proximal segment has a first cross-sectional shape, wherein the middle segment has a second cross-sectional shape, and wherein the distal segment has a third cross-sectional shape different from the second cross-sectional shape.

[0228] Example 30

[0229] A device according to any of Examples 27 to 29, wherein the cannula further includes a wedge-shaped distal end.

[0230] Example 31

[0231] A device according to any of Examples 27 to 30, wherein the proximal segment has a first stiffness and wherein the middle segment has a second stiffness different from the first stiffness.

[0232] Example 32

[0233] A device according to Example 31, wherein the second stiffness is less than the first stiffness.

[0234] Example 33

[0235] A device according to any of Examples 31 to 32, wherein the distal segment has a third stiffness different from the second stiffness.

[0236] Example 34

[0237] A device comprising: (a) a body; (b) a cannula extending distally from the body along a certain length, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and choroid of a patient's eye, wherein the cannula has a varying stiffness along the length; and (c) a needle slidably disposed in the cannula.

[0238] Example 35

[0239] The device according to Example 34, wherein the cannula includes: (i) a proximal segment having a first stiffness, (ii) a middle segment having a second stiffness different from the first stiffness, and (iii) a distal segment having a third stiffness different from the second stiffness.

[0240] Example 36

[0241] A device according to Example 35, wherein the distal segment comprises a first material, and wherein at least one of the proximal segment or the middle segment comprises a second material different from the first material.

[0242] VI. Others

[0243] To the extent that several examples herein are described in the context of an intubation guide being positioned adjacent to a formed scleral incision (23), it should be understood that other types of procedures may be employed. For example, in some variations of the procedures described herein, the intubation guide may first be secured to the eye (20); and then the scleral incision (23) may be formed after the intubation guide is secured to the eye (20). Other suitable steps and sequences that may be performed in a procedure that includes a combination of a scleral incision (23) and an intubation guide will be apparent to those of skill in the art in view of the teachings herein.

[0244] It should be understood that any version of the apparatus described herein may include various other features in addition to or in place of the features described above. By way of example only, any device herein may also include one or more of the various features disclosed in any of the various references incorporated herein by reference.

[0245] 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. Therefore, the above teachings, expressions, embodiments, examples, etc. should not be viewed in isolation from each other. In view of the teachings herein, various suitable ways in which the teachings herein may be combined will be apparent to those skilled in the art. Such modifications and variations are intended to be included within the scope of the claims.

[0246] It should be understood that any patent (publication) or other public material deemed to be incorporated by reference herein is incorporated herein in whole or in part only to the extent that the incorporated material does not conflict with existing definitions, statements, or other public materials set forth in the present disclosure. Therefore, and to the extent necessary, the disclosure explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material or portion thereof deemed to be incorporated herein but that conflicts with existing definitions, statements, or other public materials set forth herein will be incorporated only to the extent that no conflict arises between the incorporated material and the existing public materials.

[0247] The above versions can be designed to be discarded after a single use, or they can be designed for multiple uses. In either or both cases, the versions can be adjusted for reuse after at least one use. Adjustment can include any combination of steps of disassembling the device, subsequently cleaning or replacing specific parts, and subsequently reassembling. Specifically, some versions of the device can be disassembled, and any number of specific parts or parts of the device can be selectively replaced or removed in any combination. After cleaning and / or replacing specific parts, some versions of the device can be reassembled at an adjustment facility for subsequent use, or reassembled by an operator immediately before surgery. Those skilled in the art will appreciate that the adjustment of the device can utilize a variety of techniques for disassembly, cleaning / replacement, and reassembly. The use of such techniques and the resulting adjusted devices are within the scope of the present application.

[0248] By way of example only, the versions described herein can be sterilized before and / or after surgery. In one sterilization technique, the device is placed in a closed and sealed container, such as a plastic bag or a TYVEK bag. The container and device can 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 can kill bacteria on the device and in the container. The sterilized device can then be stored in the sterilization container for later use. The device can also be sterilized using any other technique known in the art, including but not limited to beta or gamma radiation, ethylene oxide, or steam.

[0249] Various embodiments of the present invention have been shown and described, and further modifications to the methods and systems described herein may be accomplished by appropriate modifications by those skilled in the art without departing from the scope of the present invention. Several such potential modifications have been mentioned, and other modifications will be apparent to those skilled in the art. For example, the examples, embodiments, geometries, materials, dimensions, ratios, steps, etc. discussed above are illustrative and not required. Therefore, the scope of the present invention should be considered in light of the appended claims, and should be understood as not being limited to the details of the structures and operations shown and described in the specification and drawings.

Claims

1. A device comprising: (a) Subject; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of an eye of a patient; as well as (c) a needle slidably disposed in the cannula, wherein the needle comprises: (i) a sharp distal tip, wherein the needle is configured to translate between a proximal position and a distal position relative to the cannula, wherein the distal tip is configured to be positioned inside the cannula when the needle is in the proximal position, and wherein the distal tip is configured to be positioned outside the cannula when the needle is in the distal position, (ii) at least one proximal bend, wherein the needle is resiliently biased to extend along at least one proximal curve passing through the at least one proximal bend, and (iii) at least one distal curve, wherein the needle is resiliently biased to extend along at least one distal curve passing through the at least one distal curve, wherein the at least one distal curve is different from the at least one proximal curve.

2. A device according to claim 1, wherein the needle further includes a distal straight portion extending along the outlet axis, wherein the distal straight portion is longitudinally inserted between the at least one distal curved portion and the sharp distal tip, and wherein the needle is elastically biased to extend along a straight path along the distal straight portion.

3. A device according to any one of claims 1 to 2, wherein the needle further includes a proximal straight portion, wherein the at least one proximal curved portion is longitudinally inserted between the proximal straight portion and the at least one distal curved portion, and wherein the needle is elastically biased to extend along a straight path along the proximal straight portion.

4. A device according to any one of claims 1 to 3, wherein the needle further includes an intermediate straight portion, wherein the intermediate straight portion is longitudinally inserted between the at least one proximal curved portion and the at least one distal curved portion, and wherein the needle is elastically biased to extend along a straight path along the intermediate straight portion.

5. A device according to any one of claims 1 to 4, wherein the at least one proximal curve portion includes a first proximal curve portion and a second proximal curve portion, and wherein the needle is elastically biased to extend along a first proximal curve and a second proximal curve passing through the first proximal curve portion and the second proximal curve portion, respectively.

6. A device according to any one of claims 1 to 5, wherein the at least one distal curve portion includes a first distal curve portion and a second distal curve portion, and wherein the needle is elastically biased to extend along a first distal curve and a second distal curve passing through the first distal curve portion and the second distal curve portion, respectively.

7. The device according to any one of claims 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 according to any one of claims 1 to 7, wherein the needle is elastically biased to define an "S" shape.

9. The device according to any one of claims 1 to 8, wherein the at least one proximal curved portion is configured to be positioned within the cannula when the needle is in the distal position.

10. The device according to any one of claims 1 to 9, wherein the at least one proximal curved portion is configured to be positioned outside the patient's eye when the needle is in the distal position.

11. The device of any one of claims 1 to 10, wherein the at least one proximal curved portion is configured to inhibit movement of the body from being transferred to the distal tip.

12. The device of any one of claims 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 claims 1 to 13, wherein the distal tip is beveled.

15. A device according to any one of claims 1 to 14, wherein the cannula is sufficiently flexible to conform to the structure and contours of the patient's eye, yet the cannula has sufficient column strength to permit the cannula to pass between the sclera and the choroid of the patient's eye without buckling.

16. The device according to any one of claims 1 to 15, further comprising: (a) a needle guide disposed between the needle and the cannula; as well as (b) a support tube partially disposed within the cannula proximal to the needle guide, wherein the support tube extends proximally from the cannula, The support tube has greater rigidity than the needle guide.

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

18. The device of any one of claims 1 to 17, wherein the cannula comprises a proximal section comprising a first material and a distal section comprising a second material different from the first material.

19. The device of any one of claims 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 of any one of claims 1 to 19, 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 any one of claims 1 to 20, wherein the at least one distal curved portion has an arc length ranging from about 2.8 mm to about 4.2 mm.

22. The device of any one of claims 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 of any one of claims 2 to 22, wherein the distal straight portion has a length ranging from about 0.56 mm to about 0.84 mm.

24. The device of any one of claims 3 to 23, wherein the proximal straight portion has a length ranging from about 20 mm to about 30 mm.

25. The device of any one of claims 4 to 24, wherein the intermediate straight portion has a length ranging from about 36.64 mm to about 54.96 mm.

26. An apparatus comprising: (a) Subject; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of an eye of a patient; as well as (c) a needle slidably disposed in the cannula, wherein the needle comprises: (i) a sharp distal tip, wherein the needle is configured to translate between a proximal position and a distal position relative to the cannula, wherein the distal tip is configured to be positioned inside the cannula when the needle is in the proximal position, and wherein the distal tip is configured to be positioned outside the cannula when the needle is in the distal position, (ii) a first curved portion, wherein the needle is resiliently biased to extend along a first curve passing through the first curved portion, and (iii) a second curved portion longitudinally spaced apart from the first curved portion, wherein the needle is resiliently biased to extend along a second curve through the second curved portion.

27. An apparatus comprising: (a) Subject; (b) a cannula extending distally from the body, wherein the cannula is flexible, wherein the cannula is sized and configured to advance between the sclera and the choroid of an eye of a patient, wherein the cannula comprises: (i) a proximal segment having a first cross-sectional area, (ii) a middle section 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 in the cannula.

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

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

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

31. The device of any one of claims 27 to 30, wherein the proximal segment has a first stiffness, wherein the intermediate segment has a second stiffness different from the first stiffness.

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

33. The device of any one of claims 31 to 32, wherein the distal segment has a third stiffness different from the second stiffness.

34. An apparatus comprising: (a) Subject; (b) a cannula extending distally from the body along a length, wherein the cannula is flexible, wherein the cannula is sized and configured to travel between the sclera and the choroid of an eye of a patient, wherein the cannula has a varying stiffness along the length; and (c) A needle slidably disposed in the cannula.

35. The device of claim 34, wherein the cannula comprises: (i) a proximal segment having a first stiffness, (ii) an intermediate section having a second stiffness different from said first stiffness, and (iii) a distal segment having a third stiffness different from said second stiffness.

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

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