Method and apparatus for subretinal delivery

Abstract

The present disclosure relates generally to devices for ophthalmic procedures, and more particularly to an apparatus for performing subretinal injections and methods of use thereof. In some embodiments, a surgical instrument for fluid injection may include a handpiece configured to be grasped by a user, the handpiece including a first lumen disposed therein, the first lumen configured to receive a fluid cartridge including one or more injection fluids, and a fluid drive system disposed within the first lumen, the fluid drive system configured to drive the fluid cartridge to receive fluid from the first lumen. The fluid drive system is configured to drive the one or more injection fluids from the fluid cartridge into the cannula. The cannula may be coupled to the handpiece and configured to be introduced into an eye. The cannula may include a second lumen extending therethrough for receiving the one or more injection fluids flowing out of the fluid cartridge, and a needle movably disposed within the second lumen, the needle configured to extend from and retract into the second lumen at a distal end of the cannula.

Description

BACKGROUND

[0001] The human eye includes three main layers: a protective outer layer of opaque white tissue called the sclera; a thin middle layer called the choroid; and the innermost light-sensitive layer called the retina, which lines the back two-thirds of the eye. The retina is composed of two sub-layers: the sensory (or neural) retina, which includes photoreceptor cells (e.g., rods and cones) that convert light images into electrochemical signals; and the retinal pigment epithelium (RPE). The cells of the RPE absorb stray light and transport oxygen, nutrients, and cellular waste between the sensory retina and the choroid to maintain homeostasis therebetween. The RPE is separated from the inner sensory retina by the subretinal space.

[0002] Certain diseases of the eye can be treated via injection into the subretinal space, including, for example, age-related macular degeneration (AMD) and retinal degenerative diseases as well as genetic defects. Typical practice requires at least two people to perform a subretinal injection. For example, the attending surgeon can guide the injection instrument (e.g., syringe / needle) and visually monitor the injection site, while a skilled surgical assistant pushes fluid from the syringe and monitors the injection volume. Accordingly, typically, a first syringe is equipped with a small gauge needle and is loaded with a non-therapeutic fluid, e.g., balanced salt solution (BSS). In the first step of the procedure, the first syringe is inserted through the retina into the subretinal space. While the surgeon manipulates the first syringe and visually monitors the injection site, the assistant manually injects the non-therapeutic fluid and monitors the injection volume. Next, the first syringe is removed from the eye.

[0003] A second syringe is equipped with a small gauge needle and is loaded with a therapeutic fluid, e.g., including a therapeutic agent. In the second step of the procedure, the second syringe is inserted through the retina into the subretinal space at approximately the same location as the first syringe. While the surgeon manipulates the second syringe and visually monitors the injection site, the assistant manually injects the therapeutic fluid and monitors the injection volume. Thus, there are many disadvantages to using handheld injection instruments to manually control injections in a two-step procedure. Some of these disadvantages are described below.

[0004] First, injections with handheld injection instruments as described above can result in retinal tears. In particular, retinal tears can result from inadvertent movement of the syringe / needle due to external forces from outside the eye when inserting the needle through the retina. The external forces can include inadvertent movement by the surgeon during manipulation of the syringe or inadvertent movement by the assistant during manual control of fluid injection.

[0005] Additionally, manually controlled fluid injection as described above can have a number of additional drawbacks. Typically, manually controlled fluid injection includes manually depressing a plunger. For example, manually controlled fluid injection can result in an incorrect injection volume, which can result in overdosing or underdosing or overstretching of the retina. In another example, manually controlled fluid injection can result in a high flow rate into the subretinal space, which can damage the retina or RPE, for example, resulting in rhegmatogenous retinal detachment with retinal morphological changes or RPE atrophy. In yet another example, manually controlled fluid injection can result in high shear forces in the needle, which can be detrimental to the biological activity of various therapeutic agents (e.g., drugs, stem cells, viral vectors) carried by the injected fluid.

[0006] Additionally, removing the first needle and inserting the second needle through the retina as described above can have additional drawbacks. For example, multiple insertions through the retina can have an impact on retinal tears. In another example, creating two different holes in the retina (one hole per injection step) increases the invasiveness of the procedure (e.g., damage to the retina) and the likelihood of fluid leakage from the subretinal space. Also, in some examples of the current manual injection method, the composition injected can remain in the subretinal space near the injection site and can not reach the desired tissue (e.g., the macula).

[0007] Each of the above-described problems can have a negative impact on the ophthalmic treatment performed and / or result in an increased safety risk. Therefore, what is needed in the art are improved devices for ophthalmic treatments, including improved apparatus and methods for subretinal delivery. SUMMARY

[0008] Embodiments of the present disclosure generally relate to devices for ophthalmic procedures, and more particularly to apparatus and methods for performing subretinal injections.

[0009] Certain embodiments of the present disclosure provide an apparatus for performing a subretinal injection into a subretinal space of an eye, the apparatus comprising: an injection needle having a proximal end and a distal end, the distal end configured to be inserted into the subretinal space at a location on a surface of a retina; an insertion device removably coupled to the injection needle; a tubing having a distal end coupled to the proximal end of the injection needle and a proximal end coupled to a fluid source, the tubing having a first lumen and a second lumen, wherein the tubing is disposed through the insertion device; a stabilizer configured to secure the injection needle at the location on the surface of the retina; and the fluid source having a first fluid reservoir containing a non-therapeutic solution and a second fluid reservoir containing a therapeutic solution, wherein the fluid source is configured to provide the non-therapeutic solution from the first fluid reservoir into the subretinal space via the first lumen, and wherein the fluid source is configured to provide the therapeutic solution from the second fluid reservoir into the subretinal space via the second lumen.

[0010] Certain embodiments of the present disclosure provide a method of performing a subretinal injection into a subretinal space of an eye, the method comprising: inserting a distal end of an injection needle into the subretinal space at a target site on a surface of a retina, the injection needle having a proximal end coupled to a distal end of a tubing, the tubing having a proximal end coupled to a fluid source, the proximal end of the injection needle further removably coupled to a distal end of an insertion device; securing the injection needle at the target site on the surface of the retina by applying pressure or fluid through a first lumen of the tubing to extend a stabilizer beyond a distal end of the first lumen to contact the surface of the retina; decoupling the insertion device from the injection needle; providing a non-therapeutic solution from the fluid source into the subretinal space via a second lumen of the tubing; and providing a therapeutic solution into the subretinal space using the fluid source via a third lumen of the tubing. BRIEF DESCRIPTION OF DRAWINGS

[0011] In order to enable a detailed understanding of the manner in which the above-recited features of the present disclosure are attained, a more particular description of the disclosure, briefly summarized above, can be had by reference to the embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only example embodiments and are therefore not to be considered limiting of its scope, as the disclosure can admit to other equally effective embodiments.

[0012] Figure 1A and Figure 1B A cross-sectional view of an eye is shown in accordance with certain embodiments described herein.

[0013] Figure 2 A cross-sectional view of an eye is shown during a subretinal injection procedure performed via a transvitreal approach in accordance with certain embodiments of the present disclosure.

[0014] Figure 3A cross-sectional view of an eye during performance of a subretinal injection procedure via a suprachoroidal approach is shown in accordance with certain embodiments of the present disclosure.

[0015] Figure 4 A perspective view of an exemplary surgical system for performing a subretinal injection procedure is shown in accordance with certain embodiments of the present disclosure.

[0016] Figure 5 A perspective view of an exemplary subretinal delivery device is shown in accordance with certain embodiments of the present disclosure.

[0017] Figure 6 A perspective view of an exemplary subretinal delivery device is shown in accordance with certain embodiments of the present disclosure.

[0018] Figure 7A and Figure 7B A schematic side cross-sectional view of a distal end of an exemplary injection cannula is shown in accordance with certain embodiments of the present disclosure.

[0019] Figures 8A to 8C A schematic side cross-sectional view of a distal end of an exemplary injection cannula is shown in accordance with certain embodiments of the present disclosure.

[0020] Figure 9A A perspective view of an exemplary injection needle is shown in accordance with certain embodiments of the present disclosure. Figures 9B to 9D A schematic side cross-sectional view of an exemplary injection needle of FIG. 10 is shown in accordance with certain embodiments of the present disclosure. Figure 9A A schematic side cross-sectional view of an exemplary injection needle of FIG. 10 is shown in accordance with certain embodiments of the present disclosure.

[0021] Figure 10A A schematic side cross-sectional view of an exemplary injection needle of FIG. 10 is shown in accordance with certain embodiments of the present disclosure. Figure 10B A schematic side view of an exemplary injection needle of FIG. 10 during use is shown in accordance with certain embodiments of the present disclosure.

[0022] Figures 11A to 11B A perspective view of an exemplary injection needle is shown in accordance with certain embodiments of the present disclosure.

[0023] Figure 12 A schematic side cross-sectional view of a distal end of an exemplary injection cannula is shown in accordance with certain embodiments of the present disclosure.

[0024] Figures 13A to 13B A schematic side cross-sectional view of an exemplary subretinal delivery device is shown in accordance with certain embodiments of the present disclosure.

[0025] Figures 14A to 14B A perspective side view of an exemplary subretinal delivery device and injection cannula is shown in accordance with certain embodiments of the present disclosure.

[0026] Figure 15A A schematic diagram illustrating a subretinal delivery system according to certain embodiments of the disclosure.

[0027] Figure 15B A portion of a delivery system according to certain embodiments of the disclosure Figure 15A An enlarged cross-sectional view of a multi-lumen tubing in

[0028] Figure 15C A top isometric view of a portion of a delivery system according to certain embodiments of the disclosure Figure 15A

[0029] Figure 15D A schematic diagram illustrating a subretinal delivery system according to certain embodiments of the disclosure Figure 15A

[0030] Figure 15E An enlarged side cross-sectional view of a portion of a delivery system shown in Figure 15D

[0031] Figure 15F A top isometric view of a portion of a delivery system according to certain embodiments of the disclosure having an alternative injection needle and stabilizer.

[0032] Figures 16A to 16E A cross-sectional view of an eye at different steps of performing a subretinal injection with a delivery system according to certain embodiments of the disclosure Figures 15A to 15E

[0033] Figures 17A to 17C A side cross-sectional view of an exemplary subretinal delivery device according to certain embodiments of the disclosure.

[0034] Figure 18A A perspective view of an exemplary subretinal delivery device according to certain embodiments of the disclosure.

[0035] Figure 18B A perspective view of another exemplary subretinal delivery device according to certain embodiments of the disclosure.

[0036] Figure 19A A perspective view of an exemplary injection cannula according to certain embodiments of the disclosure.

[0037] Figure 19B A perspective view of another exemplary injection cannula according to certain embodiments of the disclosure.

[0038] Figure 19C A cross-sectional view of an exemplary injection cannula profile according to certain embodiments of the disclosure. ​​​​

[0039] Figure 20A A cross-sectional top view of an exemplary injection cannula according to certain embodiments of this disclosure is shown.

[0040] Figure 20B and Figure 20C Certain embodiments according to this disclosure are illustrated. Figure 20A A side section view of an alternative arrangement of an exemplary injection cannula.

[0041] Figure 20D and Figure 20E This demonstrates certain embodiments of the application of this disclosure. Figure 20A Cross-sectional views of the eye at different steps of performing subretinal injection using an exemplary injection cannula.

[0042] Figure 21A and Figure 21B A perspective view of an exemplary distal tip of an injection cannula according to certain embodiments of this disclosure is shown.

[0043] Figure 21C Certain embodiments according to this disclosure are illustrated. Figure 21A and Figure 21B A side cross-sectional view of the distal end of an exemplary injection cannula.

[0044] Figure 22A A perspective view of an exemplary distal tip of an injection cannula according to certain embodiments of this disclosure is shown.

[0045] Figure 22B Certain embodiments according to this disclosure are illustrated. Figure 22A A side cross-sectional view of the distal end of an exemplary injection cannula.

[0046] Figure 23A and Figure 23B A side cross-sectional view of an exemplary internal ramp assembly for the distal end of an injection cannula, according to certain embodiments of this disclosure, is shown.

[0047] Figure 24A and 24B A schematic perspective view of an exemplary distal tip of an injection cannula according to certain embodiments of this disclosure is shown.

[0048] Figure 25 A schematic perspective view of an exemplary distal tip of an injection cannula according to certain embodiments of this disclosure is shown.

[0049] Figure 26A and Figure 26B A perspective view of an exemplary subretinal delivery device according to certain embodiments of this disclosure is shown.

[0050] Figure 27A and Figure 27B various perspective views of an exemplary subretinal delivery device according to certain embodiments of the present disclosure are shown.

[0051] Figure 28A a side cross-sectional view of an exemplary guide cannula according to certain embodiments of the present disclosure is shown.

[0052] Figure 28B a cross-sectional top view of an exemplary guide cannula according to certain embodiments of the present disclosure is shown. Figure 28A

[0053] Figure 28C and Figure 28D various cross-sectional views of an eye at different steps of performing a subretinal injection with an exemplary guide cannula according to certain embodiments of the present disclosure are shown. Figure 28A

[0054] Figure 29A a perspective view of an exemplary entry cannula according to certain embodiments of the present disclosure is shown.

[0055] Figure 29B and Figure 29C various cross-sectional views of an eye at different steps of performing a subretinal injection with an exemplary entry cannula according to certain embodiments of the present disclosure are shown. Figure 29A

[0056] Figure 30A and Figure 30B a perspective view of an exemplary entry cannula according to certain embodiments of the present disclosure is shown.

[0057] Figures 31A to 31C a schematic cross-sectional view of an exemplary subretinal delivery device according to certain embodiments of the present disclosure is shown.

[0058] Figures 32A to 32D a schematic side view of an exemplary support arm for supporting a delivery device during a subretinal injection procedure according to certain embodiments described herein is shown.

[0059] Figure 33A an exemplary operating environment during performance of a subretinal injection procedure according to certain embodiments of the present disclosure is shown.

[0060] Figure 33B various components of an operating environment in Figure 33A according to certain embodiments of the present disclosure are shown.

[0061] Figures 34A to 34D various cross-sectional views of a portion of an eye at different steps of performing an exemplary subretinal injection procedure with post-injection sealing according to certain embodiments of the present disclosure are shown. ​​​

[0062] For ease of understanding, the same reference numbers have been used in the drawings to designate the same elements common to the drawings, where possible. It is contemplated that elements and features of one embodiment can be beneficially incorporated into other embodiments without further recitation. DETAILED DESCRIPTION

[0063] In the following description, details are set forth by way of example to facilitate understanding of the disclosed subject matter. It will be apparent to one skilled in the art, however, that the disclosed implementations are exemplary and not exhaustive of all possible implementations. Thus, it should be understood that no functionality for the described examples is intended to limit the scope of the present disclosure. Those skilled in the art having the benefit of the present disclosure will readily recognize that any alteration and further modifications to the described devices, instruments, methods, and any further applications of the principles of the present disclosure are well within the scope of those skilled in the art. In particular, it is completely within the scope of the disclosure that features, components, and / or steps described for one implementation can be combined with features, components, and / or steps described for other implementations of the present disclosure.

[0064] Note that as used herein, the distal end of a component refers to the end closer to the patient’s body, while the proximal end of a component refers to the end facing away from the patient’s body.

[0065] As used herein, the term “surgical system” can refer to any surgical system, console, or device used to perform a surgical procedure. For example, the term “surgical system” can refer to a surgical console, such as a phacoemulsification console, a vitrectomy console, a laser system, or any other console, system, or device used in an ophthalmic surgery room, as known to one of ordinary skill in the art. Note that although certain embodiments are described herein with respect to ophthalmic systems, tools, and environments, the embodiments described herein are similarly applicable to other types of medical or surgical systems, tools, and environments.

[0066] As used herein, the term “about” can refer to a + / - 10% variation from a nominal value. It is understood that any value provided herein can include such variation.

[0067] Although generally described with reference to ophthalmic surgical devices and systems, the devices and systems described herein can be implemented with other devices and systems, such as devices and systems for other surgeries, without departing from the scope of the present application.

[0068] Embodiments of the present disclosure generally relate to devices and methods for ophthalmic treatment, and more particularly to apparatus and methods for performing subretinal injections. Subretinal injection generally refers to the injection of fluid or other therapeutic substances or stem cells into the subretinal space between the retina and the retinal pigment epithelium (RPE) of the eye.

[0069] It has been proposed that cell-based therapies, in which cells such as stem cells are transplanted into / near the target treatment site, can prove effective for several currently untreatable conditions involving the RPE layer, including AMD and retinitis pigmentosa (AR). Transplanting cells into the human retina has the potential to restore lost vision and provide treatment for the later stages of retinal degeneration where there is significant loss of RPE. Similarly, gene therapy, in which exogenous DNA (deoxyribonucleic acid) constructs are introduced into host cells to alter their activity, also has great potential in treating retinal diseases such as AMD, AR, choroideremia, etc. However, in order to treat retinal conditions, such techniques require access to the subretinal space. And, as described above, current techniques for injection into the subretinal space have many drawbacks, as the tissue surrounding the subretinal space is delicate and requires a high level of skill to avoid surrounding tissue.

[0070] Accordingly, embodiments of the present disclosure provide improved methods and apparatus for performing subretinal injections that mitigate or even eliminate the drawbacks associated with current techniques.

[0071] Figure 1A A cross-sectional view of an eye 100 is shown. A number of features of the eye 100 are shown here. The eye 100 includes a sclera 102 that is coupled to a retinal membrane or retina 104 by a choroid (not shown) Figure 1A ). The choroid includes connective tissue to attach the retina 104 to the inner wall of the sclera 102 at the back of the eye 100 and to provide oxygen and nutrients to the outer layer of the retina 104. The cornea 108 admits light into the eye 100, which is focused by the lens 110 through the vitreous chamber 112 onto the retina 104 containing light-activated cells that transmit signals through the optic nerve 106 to the brain.

[0072] Problems can arise in the eye that prevent the retina from developing normally and / or functioning when the retina provides signals to the brain for processing into cognizable images. Potential treatments or therapies for such eye problems can include delivering genetic material and / or stem cells into the desired area of the subretinal space, the area between the outermost surface of the retina and the retinal pigment epithelium (RPE), just above the choroid, where the immune response can be sufficiently suppressed.

[0073] The area of interest 114 on the lower portion of the eye 100 is shown in Figure 1A . The area of interest 114 is shown in more detail in Figure 1B .

[0074] Reference is now made to Figure 1BThe region of interest 114 of the eye 100 is shown in close-up to provide more detailed details of the layers of the retina 104. Note that the layers are not drawn to scale. As shown in FIG. 1 A, the eye 100 includes a cornea 102, a lens 106, a vitreous cavity 112, and a retina 104. The cornea 102 and the lens 106 are part of the anterior segment of the eye 100. The vitreous cavity 112 is filled with vitreous humor. The retina 104 is part of the posterior segment of the eye 100. The posterior segment of the eye 100 also includes a choroid 108 and a sclera 110. The choroid 108 is a vascular layer of the eye 100 that is located between the retina 104 and the sclera 110. The sclera 110 is the white of the eye 100. Figure 1A As shown in FIG. 1 B, the retina 104 includes several layers, including a main retinal layer 122, a subretinal space 124, and an opaque layer 126. The main retinal layer 122 includes an internal limiting membrane, which is in contact with the vitreous humor that fills the vitreous cavity 112. The main retinal layer 122 further includes a nerve fiber sublayer, a ganglion cell sublayer, an inner plexiform sublayer, an inner nuclear sublayer, an outer plexiform sublayer, and an outer nuclear sublayer. The main retinal layer 122 also includes an external limiting membrane and a photoreceptor sublayer. The opaque layer 126 includes the retinal pigment epithelium (RPE) and the choroid.

[0075] When a therapeutic agent is delivered to the retina 104, the therapeutic agent-containing fluid is delivered to the subretinal space 124 between the main retinal layer 122 and the retinal pigment epithelium of the opaque layer 126. Conventionally, a fine needle is used to pierce the main retinal layer 122 to allow the therapeutic agent-containing fluid to enter the subretinal space. In some examples, a bubble can then be formed by injecting, for example, balanced salt solution (BSS), and the therapeutic agent-containing fluid is then injected into the space formed by the bubble. The formation of the bubble can provide a space into which the therapeutic agent is injected without subjecting them to the fluid pressure required to form the space. In some examples, a single injection can be used to form the bubble and introduce the therapeutic agent. The introduction of the therapeutic agent-containing fluid into the subretinal space 124 between the photoreceptor sublayer and the retinal pigment epithelium can be where the immune system response to the therapeutic agent can be relatively suppressed.

[0076] During a subretinal delivery procedure, care must be taken to avoid: retinal tears, such as caused by the creation of a bubble with high retinal tension or unwanted movement of the injection needle; the injection needle piercing the retinal pigment epithelium of the opaque layer 126; damage to the retinal pigment epithelium, such as caused by an excessively high injection flow rate, which can lead to a rhegmatogenous retinal detachment with retinal morphological changes; and backflow or reflux (e.g., spillage) of the therapeutic agent into the vitreous cavity 112 through the puncture hole in the main retinal layer 122, all of which are problems associated with current subretinal injection devices and methods. Accordingly, the systems, devices, and methods of the present disclosure, embodiments of which are described herein, enable subretinal injections to be performed while avoiding the above-mentioned situations by facilitating: efficient access to the subretinal space and proper positioning of the delivery device needle tip in the retina 104; stabilization of the delivery device needle and / or delivery device handpiece to reduce the effects of unwanted user movement; and improved fluid control / manipulation of the injected fluid, reducing spillage into the vitreous cavity 112.

[0077] In general, there are two main routes for administering subretinal injections: (1) via the vitreous route, which... Figure 2 The diagram shows (2) the suprachoroidal pathway, which is shown in the diagram. Figure 3 The embodiments disclosed herein can be used in conjunction with one or both of these approaches, as discussed in more detail below.

[0078] like Figure 2 As shown in the cross-sectional view of the eye 200, in a transvitreal approach, an injection cannula 240 of the delivery device can be inserted through a valved insertion cannula 230 (or other access cannula) that is positioned through an incision (i.e., a scleral incision) in the sclera 202 of the eye 200 and guided through the vitreous cavity 212 toward the retina 204. In some embodiments, the sclera 202 can be incised using a trocar cannula, which may consist of a valved insertion cannula 230 and a trocar. Typically, a trocar cannula with a hub at its proximal end is inserted into the eye 200 (thus forming an incision) until the bottom surface of the hub contacts the sclera 202. The trocar is then removed from the eye 200, leaving the valved insertion cannula 230 in place, as... Figure 2 As shown in the diagram. In some embodiments, instead of insertion through the sclera (e.g., via the sclera), an injection cannula 240 with a valved insertion cannula 230 and thus a delivery device can be inserted through the cornea 208 into the eye 200, wherein the injection cannula 240 bypasses the lens 210 and enters the vitreous cavity 212 (e.g., via the cornea).

[0079] The injection cannula 240 of the delivery device is guided through the vitreous cavity 212 until its distal end 242 is positioned adjacent to the retina 204 and close to the target injection site in the subretinal space 224. At this point, the injection needle of the delivery device (which may be disposed within the injection cannula 240 and configured to slidably extend from the distal end 242) can be inserted through the retina 204 and into the subretinal space 224, for example, between the outermost neural layer and the retinal pigment epithelium of the retina 204, for injection.

[0080] like Figure 3As shown in the cross-sectional view of the eye 300, in the suprachoroidal approach, a flexible injection cannula 340 of the delivery device can be inserted through an incision in the sclera 302 of the eye 300 and guided through the suprachoroidal space (SCS) 332 to the target injection site without passing through the vitreous cavity 312. In some embodiments, a valved cannula or other access cannula similar to access cannula 230 can be used to facilitate the injection cannula 340's passage through the sclera 302 into the eye 300. The suprachoroidal space 332 is a potential space circumferentially traversing the posterior segment of the eye 300 between the sclera 302 and the choroid 316. Once the distal end 342 of the flexible injection cannula 340 in the suprachoroidal space 332 is positioned adjacent to the target injection site in the subretinal space 324, the injection needle 344 of the delivery device is inserted through the choroid 316 and into the subretinal space 324 for injection, compared to insertion through the retina 304 via a vitreous route. The injection needle may be disposed within the injection cannula 340 and configured to slidably extend from the distal end 342. In some embodiments, the injection cannula 340 includes a microcannula, and the injection needle 344 includes a microneedle.

[0081] Figure 4 A perspective view is shown of an exemplary surgical system 400 that can be used in conjunction with the embodiments disclosed herein to perform subretinal injection procedures. In some examples, the surgical system 400 includes a surgical system for ophthalmic procedures, such as retinal procedures and treatments, and may include, but is not limited to, surgical systems sold by Alcon, Inc., Fort Worth, Texas. The surgical system 400 includes a console 402, a controller 404 (e.g., a computer unit) having a processor and memory, and an associated display 406. The display 406 may display data, such as data relating to system operation and / or system performance during the surgical procedure, which may be arranged in a graphical user interface (GUI).

[0082] Typically, console 402 includes one or more systems or subsystems that enable the surgeon to perform various surgical procedures, such as retinal procedures. For example, subsystems may work together to perform a vitrectomy procedure prior to the injection of a therapeutic agent to provide an improved pathway to the retina. In some embodiments, a subsystem includes a control system having one or more of the following: a foot pedal subsystem 408 including a foot pedal 410 with multiple foot-actuated controls; and a device control system or subsystem 412 communicating with a handheld surgical instrument (shown as delivery device 414). Another subsystem may be used to provide tracking of the distal end of delivery device 414. This can be accomplished using optical coherence tomography (OCT), by using displacement sensors, or by other suitable mechanisms. Tracking information and other information may be provided to display 406 or a surgical microscope heads-up display. Some embodiments of console 402 may further include a vitrectomy cutter subsystem with a vitrectomy handpiece and a pump / vacuum, which may also be controlled using foot pedal 410 and / or device control subsystem 412. These subsystems of console 402 may overlap and cooperate to perform various aspects of a procedure, and may operate individually and / or independently of each other during one or more procedures. That is, some procedures may utilize one or more subsystems without using the others.

[0083] Now for reference Figure 5 According to certain embodiments of this disclosure, an exemplary subretinal delivery device 500 is illustrated in perspective. The delivery device 500 can be used as... Figure 4 The delivery device 414 of the surgical system 400, and its aspects can be combined with other delivery devices and / or components described herein without limitation.

[0084] The delivery device 500 includes a handle 502 and an injection cannula 510 having a proximal end 516 that is coupled to and extends distally from the distal end of the handle 502. The injection cannula 510, which may include a tube, is typically formed of any suitable surgical-grade material, such as a metal or thermoplastic polymer. Examples of metal materials include aluminum, stainless steel, and other metal alloys. Examples of suitable thermoplastic polymer materials include polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0085] like Figure 5As further shown, a curved or substantially straight injection needle 512 is disposed within the injection cannula 510 for piercing desired ocular tissue (e.g., the retina or choroid) to deliver fluid into the subretinal space. In an exemplary embodiment, the injection cannula 510 is a 23, 25, or 27 gauge needle, while the injection needle 512 is a finer gauge needle, such as a 38 gauge needle. However, in other embodiments, other sizes / gauges of injection cannulas and injection needles may be used.

[0086] In some embodiments, the injection needle 512 is configured to slidably extend from and retract into the distal end 511 at the distal end 514 of the injection cannula 510. This facilitates preventing damage to the injection needle 512 during insertion of the injection cannula 510 into and / or movement within the eye. This actuation of the injection needle 512 can be controlled by any suitable mechanism. Figure 5 In the example, actuation of the injection needle 512 is controlled by a toggle 540 of the handle 502, which may be directly or indirectly coupled to the injection needle 512. In some embodiments, the toggle 540 includes a sliding button or switch, wherein a user (e.g., a surgeon) slides the toggle 540 in a distal direction 542 to extend the injection needle 512 out of the injection cannula 510, and slides the toggle 540 in a proximal direction 544 to retract the injection needle 512 back into the injection cannula 510.

[0087] In some embodiments, the sliding toggle 540 may also be lockable, allowing the injection needle 512 to be secured in either an extended or retracted position. Locking the injection needle 512 prevents accidental movement of the needle during retinal procedures (e.g., subretinal injections), thereby reducing the risk of unwanted tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 540 for adjustment, a user can repeatedly press the toggle 540, allowing the user free to slide the toggle 540 and thus freely extend or retract the injection needle 512. In this example, the toggle 540 may be movable only when pressed (e.g., activated) by the user. Correspondingly, releasing the toggle 540 can cause the toggle 540 to rise and lock in place, thereby locking the injection needle 512 in position. This button-locking mechanism may be facilitated in part by a spring rod disposed with the handle 502 and one or more tracks including grooves or notches along which the toggle 540 can slide.

[0088] like Figure 5As further shown, in some embodiments, a flexible fluid conduit 520 for supplying injection fluid (e.g., non-therapeutic solutions and / or therapeutic solutions) to the delivery device 500 may be disposed through the proximal end 506 of the handle 502 and fluidly coupled to the injection needle 512 within the handle 502. In some embodiments, the fluid conduit 520 may be coupled to the proximal end 506 of the handle 502, or to another fluid conduit within the handle 502 (described elsewhere herein). Typically, the fluid conduit 520 includes a supply line from a fluid source ( Figure 5 Injection fluids (e.g., non-therapeutic and / or therapeutic solutions, not shown) can be supplied to delivery device 500 via the supply line for delivery to the eye. In some embodiments, fluid conduit 520 includes a multi-lumen conduit providing multiple parallel flow paths from a separate fluid reservoir of the fluid source to injection needle 512, allowing multiple fluid types to be injected using only a single needle. In some embodiments, the fluid source includes a fluid system that can be coupled to fluid conduit 520 via connector 522 (e.g., a Luer lock or other male-female connector). In some other embodiments, handle 502 may include an actuable lumen fluidly coupled to injection cannula 510 and receiving the injection fluid. In such embodiments, subretinal delivery device 500 may not be coupled to any external fluid conduit.

[0089] In another embodiment, to simplify fluid preparation for subretinal injection, injection fluid can be supplied to delivery device 500 from a pre-filled cartridge, which can be coupled to a fluid drive system of delivery device 500 or to an external fluid system connected to delivery device 500 via fluid conduit 520. In some embodiments, the pre-filled cartridge includes a single lumen containing premixed therapeutic material. In other embodiments, the pre-filled cartridge includes two or more lumens containing unmixed therapeutic material, which can be automatically or semi-automatically mixed within, for example, a fluid system or delivery device prior to performing subretinal injection. The cartridge for the therapeutic agent is described in further detail below.

[0090] Now for reference Figure 6 According to certain embodiments of this disclosure, another exemplary subretinal delivery device 600 is shown in a perspective view. Delivery device 600 is substantially similar to delivery device 500 and can also be used as... Figure 4 The delivery device 414 of the surgical system 400. Various aspects of the delivery device 600 can also be combined with other delivery devices and / or components described herein without limitation. However, unlike the delivery device 500, the handle of the delivery device 600 is "rotatable," as described below.

[0091] like Figure 6As shown, the delivery device 600 includes a handle 602, a tubular injection cannula 610, and a curved or substantially straight injection needle 612 (a curved injection needle 612 is shown), the tubular injection cannula having a proximal end 616 coupled to and extending from the distal end 604 of the handle 602, the injection needle being disposed within the injection cannula 610. In some embodiments, a flexible fluid conduit 620 for supplying injection fluid (e.g., non-therapeutic solutions and / or therapeutic solutions) to the delivery device 600 may be disposed through the proximal end 606 of the handle 602 and fluidly coupled to the injection needle 612 within the handle 602. Alternatively, the fluid conduit 620 may be coupled to the proximal end 606 of the handle 602, or to another fluid conduit within the handle 602. In some embodiments, the fluid conduit 620 includes a multi-lumen conduit. Like fluid conduit 520, fluid conduit 620 includes a connector 622 located at the proximal end of fluid conduit 620 for connection to a fluid source, such as a fluid system integrated with a surgical console.

[0092] The injection needle 612 is configured to slidably extend from and retract into the distal end 611 at the distal end 614 of the injection cannula 610 to prevent damage to the injection needle 612. Figure 6 In this delivery device 600, actuation of the injection needle 612 is controlled by a circumscribing actuator 640, which can be fully externally attached to or wrapped around the handle 602 (e.g., around the longitudinal main axis X of the handle 602) near its distal end 604, and can be directly or indirectly coupled to the injection needle 612 within the handle 602. Similar to the actuator 540 described above, sliding the actuator 640 in the distal direction 642 causes the injection needle 612 to extend from the injection cannula 610, while sliding the actuator 640 in the proximal direction 644 causes the injection needle 612 to retract into the injection cannula 610. Because the circumscribing actuator 640 wraps around the entire handle 602, the user can control the extension and retraction of the injection needle 612 when the delivery device 600 is set to any given rotation angle in the hand of the user (e.g., a surgeon). Accordingly, the handle 602 of the delivery device 600 can be described as “rotatable”. This rotatability is particularly advantageous for curved injection needles 612. For example, when using such a curved injection needle 612, it may be beneficial for the user to rotate the handle 602, and thus the injection needle 612 coupled to the handle, to one side or the other to accurately deliver fluid to the target injection site. Therefore, in these cases, the external actuator 640 facilitates controlling the extension / retraction of the injection needle 612 independently of the rotation of the handle.

[0093] In some embodiments, instead of a series of toggle members surrounding the handle 602, the external toggle member 640 includes a plurality of buttons (e.g., three, four, or more buttons) distributed symmetrically or asymmetrically around the handle 602. In some embodiments, the external toggle member 640 is lockable, allowing the injection needle 612 to be secured in either an extended or retracted position.

[0094] Figure 7A and Figure 7B A schematic side cross-sectional view of the distal end 714 of an exemplary injection cannula 710 according to certain embodiments of this disclosure is shown. The injection cannula 710 is an exemplary tubular injection cannula that can be used with… Figure 5 and Figure 6 Delivery devices 500 and 600, or other delivery devices for subretinal injection as described herein, may be used together. Aspects of the injection cannula 710 may be combined with other delivery devices and / or components described herein without limitation.

[0095] As shown, an injection needle 712 is disposed within an injection cannula 710 and configured to slidably extend from and retract from its distal end 714. Within the injection cannula 710, the proximal end 706 of the injection needle 712 is coupled to an internal fluid shaft (or connector) 720, which provides a fluid connection between the injection needle 712 and a flexible fluid conduit for supplying injection fluid to the injection needle 712. In such an embodiment, the internal fluid shaft 720 is configured to slidably translate within the injection cannula 710 to facilitate the extension and retraction of the injection needle 712. Alternatively, the injection needle 712 may be directly coupled to a fluid conduit. In some embodiments, such a fluid conduit includes a multi-lumen conduit providing multiple parallel flow paths from a separate fluid reservoir of a fluid source to the injection needle 712, allowing injection to be performed using only a single needle.

[0096] An annular insert 730 is also disposed within the injection cannula 710, at the distal end 714 of the injection cannula, and surrounding the injection needle 712. The annular insert 730 is externally connected to the injection needle 712 and acts as a mechanical reinforcer or stabilizer for the injection needle 712 by preventing or reducing lateral movement of the injection needle during use. In some embodiments, the stiffness of the injection needle 712 can be adjusted or controlled by extending or retracting the injection needle 712 from or through the injection cannula 710 and through the annular insert 730. For example, to increase the flexibility of the injection needle 712 and reduce its stiffness, the injection needle 712 can be extended through the annular insert 730 and beyond the injection cannula 710, such as... Figure 7AAs shown in the diagram. Exposing a larger portion of the injection needle 712 from the injection cannula 710 (e.g., forming a longer, "free-dangling" needle) allows for greater needle flexibility. Conversely, to increase the rigidity of the injection needle 712 for tissue puncture, the injection needle 712 can be retracted through the annular insert 730 and directed / entered into the injection cannula, as shown in the diagram. Figure 7B As shown in the diagram. Reducing the length of the injection needle 712 exposed from the injection cannula 710 (e.g., forming a shorter “free-dangling” needle) reduces the flexibility of the needle.

[0097] Accordingly, the adjustable stiffness of the injection needle 712 allows the user (e.g., a surgeon) to adjust it to a high stiffness so that the needle 712 can easily puncture during subretinal injection. Higher stiffness reduces the amount of pressure required to puncture the retina (or other ocular tissue / membrane) and further reduces the risk or occurrence of tissue damage caused by traction of the injection needle 712 on such tissue during puncture. Simultaneously, the adjustable stiffness of the injection needle 712 allows the user to adjust it to a low stiffness (or high flexibility) after puncturing the desired tissue or membrane (e.g., the retina) to reduce the risk of tissue damage caused by accidental movement or tremors of the user. The extension and retraction of the injection needle 712 to adjust needle stiffness can be controlled by any suitable mechanism, including Figure 5 and Figure 6 The institutions described in the text.

[0098] The annular insert 730 is typically formed of any suitable surgical-grade material, such as a metallic or thermoplastic polymeric material that facilitates the extension and retraction of the injection needle 712 from and back into the injection cannula 710. Examples of metallic materials include aluminum, stainless steel, and other metal alloys. Examples of suitable thermoplastic polymeric materials include polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0099] like Figure 7A and Figure 7B As shown, the annular insert 730 can be fixedly connected to the inner wall 708 of the injection cannula 710, and therefore has a diameter 710 that corresponds to the inner diameter of the injection cannula 710. ID Basically, the matching outer diameter is 730. OD In some embodiments, the distal surface 732 of the annular insert 730 is flush with the distal surface 740 of the injection cannula 710. To facilitate the extension and retraction of the injection needle 712 from and into the injection cannula 710, and to reduce the air gap between the injection needle 712 and the injection cannula 710, the annular insert 730 may have an inner diameter 730 that substantially matches the outer diameter of the injection needle 712. ID For example, an inner diameter of 730 IDIt can be equal to or approximately equal to the outer diameter of a 38 gauge needle.

[0100] Figures 8A to 8C A schematic side cross-sectional view of another distal end 814 of an exemplary injection cannula 810 according to certain embodiments of this disclosure is shown. The injection cannula 810 is an exemplary injection cannula that can be used with… Figure 5 and Figure 6 Delivery devices 500 and 600, or other delivery devices for subretinal injection as described herein, may be used together. Aspects of the injection cannula 810 may be combined with other delivery devices and / or components described herein without limitation.

[0101] As shown in the figure, the injection needle 812 is disposed within the tubular injection cannula 810 and configured to slidably extend from and retract from its distal end 814. Similar to... Figures 7A to 7B In one embodiment, the proximal end 806 of the injection needle 812 is coupled to an internal fluid shaft 820, which serves as a fluid connection between the injection needle 812 and a flexible fluid conduit connected to a fluid source. In such an embodiment, the internal fluid shaft 820 may be slidably disposed within the cannula 810 to facilitate the extension and retraction of the injection needle 812. However, in some embodiments, the injection needle 812 may be directly coupled to the fluid conduit.

[0102] exist Figures 8A to 8C In this embodiment, the injection needle 812 comprises a pre-defined, curved needle tip formed of an elastic (or flexible) material. In some embodiments, the injection needle 812 may be formed of a hyperelastic material (such as nitinol). During subretinal injection, the use of a curved and elastic material allows the injection needle 812 to have an adjustable insertion angle, thereby facilitating easier positioning within the subretinal space and easier access to peripheral retinal areas that would typically be inaccessible with a straight injection needle. In some examples, the adjustable insertion angle of the injection needle 812 helps reduce damage to tissues beneath the subretinal space (such as the retinal pigment epithelium (RPE)) because it allows entry into the subretinal space at a lower angle, thus improving the safety of subretinal injection.

[0103] In some embodiments, the insertion angle (or curvature) of the injection needle 812 can be adjusted or controlled by extending or retracting the injection needle 812 from or into the injection cannula 810. In some embodiments, the curvature of the injection needle 812 can be increased by extending the injection needle 812 from the injection cannula 810, such as... Figures 8A to 8C As shown in the image. Note that in... Figures 8A to 8CIn some embodiments, to facilitate bending or flexing of the injection needle 812 as it extends from the injection cannula 810, the injection cannula 810 may not include an annular insert at its distal end 814. However, in some embodiments, an annular insert similar to the annular insert 730 may be used.

[0104] refer to Figure 8A In the retracted state, the injection needle 812 can be substantially straight or only slightly curved, as its curvature is limited by the inner diameter of the injection cannula 810. Figure 8B In this process, the injection needle 812 extends partially from the injection cannula 810, and its curvature begins to increase as it exits the injection cannula 810. Figure 8C In this embodiment, the injection needle 812 extends fully from the injection cannula 810 and is positioned at its maximum curvature as its elastic material deforms back to its original shape. Therefore, in the example shown, the greater the distance the injection needle 812 extends beyond the injection cannula 810, the larger the curvature angle C exhibited by the injection needle 812. In some embodiments, the maximum curvature angle C of the injection needle 812 relative to the principal longitudinal axis of the injection cannula 810 is 90°.

[0105] Figures 9A to 9D Various views of an exemplary injection needle 912 according to certain embodiments of this disclosure are shown. The injection needle 912 is an exemplary injection needle that can be used with any injection cannula and / or delivery device for subretinal injection as described herein. Therefore, aspects of the injection needle 912 can be combined with other delivery devices and / or components described herein without limitation. For illustrative purposes, the injection needle 912 is shown disposed within a tubular injection cannula 910.

[0106] As shown in the figure, the injection needle 912 includes a stepped needle. In other words, the injection needle 912 includes two or more portions with different outer diameters, wherein the outer diameter gradually increases in a stepwise (i.e., gradually increasing) manner along the length of the injection needle 912 in the proximal direction. In some embodiments, such as Figures 9A to 9D In the middle, the injection needle 912 includes a first outer diameter 920 OD The first distal portion 920 and having a second outer diameter 930 OD The second proximal portion 930. In such an embodiment, the outer diameter 930 of the proximal portion 930 OD The outer diameter of the distal portion is 920. ODFor example, the distal portion 920 may have a specification of 38, and the proximal portion 930 may have a specification of 37, 36, 35, 34, 33, 32, 31, 30, or larger. In another example, the distal portion 920 may have a specification of 41, and the proximal portion 930 may have a specification of 40, 39, 38, 37, 36, 35, 34, 33, or larger. In yet another example, the distal portion 920 may have a specification of 41, and the proximal portion 930 may have a specification of 38 or larger.

[0107] By ensuring that the injection needle 912 does not penetrate the subretinal space and enter the underlying tissue, thereby preventing damage to such tissue, the stepped external shape of the injection needle 912 contributes to improved safety during subretinal injections. For example, as Figure 9B As shown, when performing subretinal injection via the transvitreal route, the proximal portion 930 can act as a mechanical stop and prevent the distal portion 920 of the injection needle 912 from penetrating the subretinal cavity 928 and piercing the RPE 926. Accordingly, in such an embodiment, the distal portion 920 may have a length along the main longitudinal axis of the injection needle 912 corresponding to the thickness of the retina 924, and the proximal portion 930 may have a length along the main axis of the injection needle 912 corresponding to the remaining length of the injection needle 912. Additionally, the stepped external shape of the injection needle 912 (e.g., the wider proximal portion 930) can prevent fluid injected into the subretinal cavity 928 from leaking or escaping from the subretinal cavity 928 through the puncture wound formed by the injection needle 912.

[0108] In some embodiments, in addition to having a stepped external shape, the injection needle 912 may also have a stepped internal shape. For example, as... Figure 9C As shown, the injection needle 912 may include a smaller first inner diameter 940 substantially corresponding to the distal portion 920 and a larger second inner diameter 950 substantially corresponding to the proximal portion 930. Utilizing a stepped inner diameter can reduce the risk or occurrence of damage to tissues surrounding the subretinal space (e.g., RPE) during fluid injection, because the transition from the larger inner diameter 950 to the smaller inner diameter 940 creates reduced fluid resistance, thereby reducing the total force of the fluid jet dispensed by the injection needle 912. However, in some other embodiments, the injection needle 912 may include a single inner diameter 960 extending through the length of the injection needle 912, such as... Figure 9D As shown in the image.

[0109] In some embodiments, the stepped shape of the injection needle 912 is formed by shrinking or compressing the distal portion 920 into a desired shape / size. In some embodiments, the stepped shape of the injection needle 912 is formed by expanding the proximal portion 930 into a desired shape / size. In some embodiments, the stepped shape of the injection needle 912 is formed by assembling two separate tubes together using any suitable technique, including welding or the use of adhesives.

[0110] Figures 10A to 10B Various views of another injection needle 1012 according to certain embodiments of this disclosure are shown. The injection needle 1012 is an exemplary injection needle that can be used with any injection cannula and / or delivery device described herein. Therefore, aspects of the injection needle 1012 can be combined with other delivery devices and / or components described herein without limitation. For illustrative purposes, the injection needle 1012 is shown disposed within a tubular injection cannula 1010 and coupled at its proximal end 1006 to an internal fluid shaft 1020 within the injection cannula 1010.

[0111] like Figure 10A As shown, the injection needle 1012 includes a sealing element 1030 disposed around a portion of its distal end 1004. In some embodiments, the sealing element 1030 includes an annular ring formed around (externally) the injection needle 1012. However, other configurations are also contemplated. Typically, the sealing element 1030 has an outer dimension S that is larger than the outer dimension I of the injection needle 1012 but smaller than the inner diameter C of the injection cannula 1010, such that in embodiments where the injection needle 1012 is configured to extend from / retract into the injection cannula 1010, the sealing element 1030 can be fitted within the injection cannula 1010. In some embodiments, the sealing element 1030 is formed of a flexible, resilient, or soft material with sealing properties to prevent damage to the tissue it contacts. For example, the sealing element 1030 may comprise silicone or a rubber-based material.

[0112] In some embodiments, the segment 1040 of the injection needle 1012 distal to the sealing element 1030 may have a length L along the main longitudinal axis A of the injection needle 1012, which corresponds to the retina ( Figure 10B The thickness (marked as 1024) is [notation missing]. This length L, combined with the increased outer dimensions of the sealing element 1030 relative to the injection needle 1012, ensures that the injection needle 1012 does not penetrate the subretinal space during injection. Figure 10B Marked as 1028) and enter the tissues below, such as RPE ( Figure 10B (marked as 1026). Accordingly, in such an example, the sealing element 1030 acts as a... Figures 9A to 9CThe stepped injection needle has a similar mechanical stop to the proximal portion, which reduces the risk of damage to tissues below the subretinal space 1028.

[0113] In some embodiments, the sealing element 1030 can prevent fluid injected into the subretinal cavity 1028 from leaking or escaping from the subretinal cavity 1028 through the puncture wound formed by the injection needle 1012. For example, as Figure 10B As shown, the sealing element 1030 can prevent the injected fluid from escaping through the retina 1024.

[0114] Figures 11A to 11B Various views of another injection needle 1112 according to certain embodiments of this disclosure are shown. Injection needle 1112 is an exemplary injection needle that can be used with any injection cannula and / or delivery device for subretinal injection as described herein. Therefore, aspects of injection needle 1112 can be combined with other delivery devices and / or components described herein without limitation.

[0115] like Figure 11A As shown, the injection needle 1112 includes a beveled tip 1130 at its distal end 1104, which has a port 1134. At least a portion of the end face 1132 of the beveled tip 1130 is beveled or at a non-orthogonal angle relative to the principal longitudinal axis A of the injection needle 1112. That is, a portion or the entire end face 1132 is not coplanar with a plane perpendicular to the principal axis A of the injection needle 1112. In some embodiments, a portion or the entire end face 1132 of the injection needle 1112 is positioned at an angle between about 0° and about 90° relative to a plane perpendicular to the principal axis A, such as at an angle between about 30° and about 60° relative to such a plane. In some embodiments, the end face 1132 is planar. In some embodiments, the end face 1132 is curved or includes two or more non-planar portions. The beveled tip 1130 provides reduced traction and facilitates tissue penetration (such as the retina) to reach the subretinal space during subretinal injection. Therefore, the oblique tip 1130 helps reduce tearing of the ocular tissue during injection, thereby improving the safety of this procedure compared to using other tip shapes.

[0116] In some embodiments, the injection needle 1112 further includes a side port 1136 disposed through the sidewall 1138 of the injection needle 1112. While the port 1134 through the beveled end 1130 serves as the main outlet for the injection fluid, the side port 1136 can be used as an auxiliary outlet for such injection fluid. Accordingly, including the side port 1136 is advantageous in reducing the fluid jet of injection fluid passing through / from the port 1134 during injection, which may be disposed adjacent to and / or facing one or more tissues during injection. For example, during transvitrectomy injection, the port 1134 may be positioned adjacent to and facing the RPE in the subretinal space. Thus, during injection, the injected fluid would be directed to the RPE, which could potentially damage the RPE if the injection force is too great. By including the side port 1136, a portion of the injection fluid is directed / flows to the periphery, thereby reducing the fluid jet directed to the RPE and minimizing any damage thereby.

[0117] In another embodiment, the injection needle 1112 may not include the port 1134 passing through the beveled end 1130, but may only include the side port 1136 as the outlet for the injected fluid. In such an embodiment, the injection needle 1112 may be referred to as a "closed" needle because the beveled end 1130 may include a solid closed end face 1132.

[0118] Figure 12 A schematic side cross-sectional view of the distal end 1214 of an exemplary injection cannula 1210 according to certain embodiments of this disclosure is shown. The injection cannula 1210 is an exemplary tubular injection cannula that can be used with any delivery device for subretinal injection as described herein. Therefore, aspects of the injection cannula 1210 can be combined with other delivery devices and / or components described herein without limitation.

[0119] As shown, an injection needle 1212 is disposed within an injection cannula 1210 and coupled to an inner fluid shaft 1220 extending along the length of an inner channel 1221 of the injection cannula 1210. The inner channel 1221 of the injection cannula 1210 extends from a proximal end to a distal end 1214. The injection needle 1212 and the inner fluid shaft 1220 are configured to slidably extend from and retract into the distal end 1214, for example, when an actuation element operably coupled to the inner fluid shaft 1220 is actuated. However, in other embodiments, the injection needle 1212 may be directly and slidably coupled to the injection cannula 1210 without the inner fluid shaft 1220. In such embodiments, the injection needle 1212 may extend along the entire length of the inner channel 1221.

[0120] Similar to the injection cannula 1210, the internal fluid shaft 1220 and the injection needle 1212 each include their own internal channels 1222 and 1223. Figure 12 In the example, inner channel 1222 extends from the proximal end of inner fluid axis 1220 to the distal end 1244 of inner fluid axis 1220, and inner channel 1223 extends from the proximal end 1224 of injection needle 1212 to its distal end 1226. During subretinal injection, injection fluid (e.g., non-therapeutic solution and / or therapeutic solution) from a fluid source in fluid communication with injection needle 1212 flows through inner channels 1221, 1222, and / or 1223 and is dispensed from the distal end 1226 of injection needle 1212.

[0121] Each internal channel 1221, 1222, and 1223 is at least partially defined by the inner walls 1230, 1232, or 1234 of the injection cannula 1210, the internal fluid shaft 1220, and the injection needle 1212. Figure 12 In this embodiment, the inner walls 1232 and 1234 each have a coating 1240 or 1242 disposed thereon. Coatings 1240 and 1242 are configured to reduce surface adhesion and / or other effects of the surfaces of the inner walls 1232 and 1234 on the injection fluid flowing through the inner fluid axis 1220 and the injection needle 1212. Accordingly, coatings 1240 and 1242 facilitate reducing fluid resistance through the inner fluid axis 1220 and the injection needle 1212, thereby allowing lower pressures to be applied to generate the necessary fluid flow for subretinal injection.

[0122] In some embodiments, coatings 1240 and / or 1242 comprise polymer brush coatings, such as those formed from poly(ethylene oxide) (PEO), poly(methyl methacrylate) (PMMA), poly(hydroxyethyl methacrylate) (PHEMA), combinations thereof, etc. In some embodiments, coatings 1240 and / or 1242 comprise fluoropolymer coatings, such as those formed from polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), perfluoroalkoxy (PFA), trifluorochloroethylene (E-CTFE), combinations thereof, etc. In some embodiments, coatings 1240 and / or 1242 comprise polyetheretherketone (PEEK) coatings. Other functionalized coatings are also contemplated. Typically, coatings 1240 and / or 1242 have a thickness between about 1 nm and about 1000 nm, for example, between about 1 nm and about 500 nm, for example, between about 1 nm and about 100 nm. In some embodiments, coatings 1240 and 1242 are substantially identical. For example, coatings 1240 and 1242 may include the same type, material, thickness, etc. In some other embodiments, coatings 1240 and 1242 are different. For example, coatings 1240 and 1242 may include different types, materials, thicknesses, etc.

[0123] It should be noted that when the injection needle 1212 is directly connected to the injection cannula 1210 without the internal fluid shaft 1220, the coating 1240 can be provided along the inner wall 1230 of the injection cannula 1210.

[0124] Now for reference Figures 13A to 13B According to certain embodiments of this disclosure, another exemplary subretinal delivery device 1300 is shown in a schematic side cross-sectional view. The delivery device 1300 can be used as, for example... Figure 4 The delivery device 414 of the surgical system 400 is not limited to any injection cannula, injection needle or other component described herein.

[0125] The delivery device 1300 includes a handle 1302, a tubular injection cannula 1310, and a curved or substantially straight injection needle 1312 (a straight injection needle 1312 is shown). The tubular injection cannula has a proximal end 1316 coupled to and extending distally from the distal end of the handle 1302. The injection needle is disposed within the injection cannula 1310 and configured to slidably extend from and retract into the injection cannula 1310 by actuation of an actuating element 1362. In some embodiments, the injection needle 1312 is coupled to an internal fluid shaft at least partially disposed within the cannula 1310 for fluid connection between the injection needle 1312 and the actuating element 1362 or a fluid conduit. In such embodiments, the internal fluid shaft may be slidably disposed within the cannula 1310 to facilitate the extension and retraction of the injection needle 1312 when the actuating element 1362 is actuated. In some embodiments, the handle 1302 is rotatable, as referenced above. Figure 6 Described.

[0126] The injection needle 1312 is fluidly coupled directly or indirectly at its proximal end 1324 to the distal end 1346 of a flexible first fluid conduit 1340 disposed within the handle 1302. In some embodiments, the first fluid conduit 1340 is made of silicone, thermoplastic polyurethane (TPU), combinations thereof, or other flexible materials. The proximal end 1344 of the first fluid conduit 1340 terminates at or substantially near the proximal end 1306 of the handle 1302, where the first fluid conduit 1340 is fluidly coupled directly or indirectly to the distal end 1356 of a flexible second fluid conduit 1350 having a proximal connector 1352 for coupling to a fluid source. Similar to the first fluid conduit 1340, in some embodiments, the second fluid conduit 1350 is made of silicone, thermoplastic polyurethane (TPU), combinations thereof, or other flexible materials. The second fluid conduit 1350 is configured as a supply line to supply injection fluid (e.g., non-therapeutic and / or therapeutic solutions) from a fluid source to the delivery device 1300, and more specifically, to the first fluid conduit 1340 and the injection needle 1312. In some embodiments, the fluid source includes a fluid system that can be coupled to the second fluid conduit 1350 via a connector 1364 (e.g., a Luer lock or other male-female connector). In operation, the first fluid conduit 1340 facilitates the disconnection of the injection needle 1312 from the second fluid conduit 1350, thereby stopping any mechanical stress (e.g., pulling) on ​​the second fluid conduit 1350 at the handle 1302. This prevents such mechanical stress from acting on the injection needle 1312, which could otherwise cause the injection needle 1312 to involuntarily withdraw from or retract into the injection cannula 1310.

[0127] In some embodiments, the first fluid conduit 1340 and the second fluid conduit 1350 have the same type, material, diameter, etc. In some other embodiments, the first fluid conduit 1340 and the second fluid conduit 1350 have different types, materials, diameters, etc. For example, in some embodiments, the first fluid conduit 1340 may include a more flexible / flexible material compared to the second fluid conduit 1350. In some embodiments, the first fluid conduit 1340 has a smaller or larger diameter compared to the second fluid conduit 1350.

[0128] exist Figures 13A to 13BIn this configuration, the base 1360 of the lockable actuator 1362 fluidly connects the proximal end 1324 of the injection needle 1312 to the distal end 1346 of the first fluid conduit 1340. However, other connection arrangements and / or mechanisms between the injection needle 1312 and the first fluid conduit 1340 are contemplated. Similarly, the proximal end 1344 of the first fluid conduit 1340 is indirectly but fluidly connected to the distal end of the second fluid conduit 1350 via a connector 1364, which is fixedly disposed at the proximal end 1306 of the handle 1302. The connector 1364 may comprise any suitable type of connector, such as a male-to-male connector. Likewise, other connection arrangements and / or mechanisms between the first fluid conduit 1340 and the second fluid conduit 1350 are contemplated.

[0129] The actuator 1362 can be manually controlled by the user to actuate the injection needle 1312 via any of the actuation mechanisms described herein, such as extending / retracting it from the injection cannula 1310. As described above, the actuator 1362 is lockable, and therefore, when the actuator 1362 is released, it is locked in place. Accordingly, the user can adjust the position of the injection needle 1312 by manually actuating the actuator 1362, and can then lock the injection needle 1312 in place by releasing the actuator 1362. However, because the injection needle 1312 is disconnected from the external second fluid conduit 1350, the movement and / or positioning of the injection needle 1312 of the subretinal delivery device 1300 remains unaffected by the second fluid conduit 1350. Therefore, the movement of the second fluid conduit 1350 has no effect on the needle position (or vice versa), and will not interrupt or undesirably cause the repositioning of the injection needle 1312 after the user has positioned / locked the injection needle 1312 using the toggle 1352.

[0130] Figures 14A to 14B A perspective side view of an exemplary subretinal delivery device 1400 having an articulated tubular injection cannula 1410 according to certain embodiments of this disclosure is shown. The delivery device 1400 having the injection cannula 1410 can be used as, for example... Figure 4 The delivery device 414 of the surgical system 400 or other surgical systems for subretinal injection as described herein. Aspects of the delivery device 1400 may be combined with other delivery devices and / or components described herein without limitation.

[0131] like Figure 14AAs shown, the delivery device 1400 further includes a handle 1402, wherein a proximal end 1416 of the injection cannula 1410 is coupled to a distal end 1404 of the handle 1402 and extends distally from the distal end of the handle. Within the injection cannula 1410 is a curved or substantially straight injection needle 1412 (a straight injection needle 1412 is shown), configured to slidably extend from and retract into the injection cannula 1410 by actuation of an actuating element 1440. In some embodiments, the injection needle 1412 is coupled to an internal fluid shaft at least partially disposed within the cannula 1410, which serves as a fluid connection between the injection needle 1412 and the actuating element 1440 or a fluid conduit. In such embodiments, the internal fluid shaft may be slidably disposed within the cannula 1410 to facilitate the extension and retraction of the injection needle 1412 when the actuating element 1440 is actuated. In some embodiments, the handle 1402 is rotatable, as referenced above. Figure 6 Described.

[0132] In some embodiments, a flexible fluid conduit 1420 for supplying injection fluid (e.g., non-therapeutic and / or therapeutic solutions) to the delivery device 1400 may be disposed through the proximal end 1406 of the handle 1402 and fluidly coupled to the injection needle 1412 within the handle 1402. Alternatively, the fluid conduit 1420 may be coupled to the proximal end 1406 of the handle 1402 or to another fluid conduit within the handle 1402. In some embodiments, the fluid conduit 1420 includes a multi-lumen conduit that provides multiple parallel flow paths from a separate fluid reservoir of a fluid source to the injection needle 1412, allowing injection to be performed using only a single needle.

[0133] The injection cannula 1410, which may include a tube, and / or the injection needle, is typically formed of any suitable surgical-grade material, such as a metallic material or a thermoplastic polymeric material. Examples of metallic materials include aluminum, stainless steel, and other metal alloys. Examples of suitable thermoplastic polymeric materials include polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0134] exist Figure 14A and Figure 14BIn the example, the injection cannula 1410 is controllably hinged. In other words, the injection cannula 1410 can be controllably bent by manual adjustment by the user. To facilitate the hinged nature of the injection cannula 1410, the injection cannula 1410 may include a plurality of features 1460 formed in the outer surface 1462 of the injection cannula 1410, which allow the injection cannula 1410 to be flexible in one or more directions orthogonal to the main longitudinal axis A of the injection cannula 1410. For example, in some embodiments, features 1460 may be formed in the outer surface 1462 such that the injection cannula 1410 can be hinged in opposite directions for one or two perpendicular axes B and C arranged along a plane perpendicular to the main axis A. In such an example, two or more sets of features 1460 may be formed on the opposite surface of the outer surface 1462 of the injection cannula 1410. In some embodiments, feature 1460 includes, for example, slots, slits, or other suitable features etched or cut (e.g., laser-etched or cut) along the length of injection cannula 1410 into outer surface 1462 to facilitate biasing injection cannula 1410 into a curved position.

[0135] The hinge or bend of the injection cannula 1410 can be manually controlled by one or more actuators 1464 separate from the actuator 1440. In some embodiments, the one or more actuators 1464 may be actuators of the same type as actuator 1440. In some embodiments, the one or more actuators 1464 may be actuators of a different type compared to actuator 1440. Figure 14A In this embodiment, a plurality of actuating elements 1464 are arranged around the circumference of the handle 1402. In this embodiment, each of the plurality of actuating elements 1464 can control the bending of the injection cannula 1410 in different directions. Typically, the one or more actuating elements 1464 can be coupled to one or more wires disposed within the handle 1402 and coupled to different points within the injection cannula 1410. These wires act on the injection cannula 1410 when manipulated by the user via the actuating elements 1464, causing the injection cannula 1410 to hinge in the corresponding direction. Therefore, manipulation of the wires can produce a curvature of the injection cannula 1410 in a desired direction.

[0136] Figure 15A A schematic diagram of an exemplary underretinal delivery system 1500 according to certain embodiments of this disclosure is shown. The delivery system 1500 can be used with, for example... Figure 4 The delivery device 414 of the surgical system 400 or other surgical systems for subretinal injection as described herein may be used. Aspects of the delivery system 1500 may be combined with other delivery devices and / or components described herein without limitation.

[0137] Typically, the delivery system 1500 includes an injection needle attached to a tubing that can be detached from the handle and secured within the eye using a stabilizer, eliminating the need to hold the injection device in place throughout the procedure. This prevents unwanted movement of the injection needle that would otherwise occur when holding the injection device. Furthermore, in some examples, the tubing of the delivery system 1500 may be a multi-lumen tubing that provides multiple parallel flow paths from a separate fluid reservoir to the injection needle, allowing injections to be performed using only a single needle. Requiring only one needle to be inserted through the retina reduces the risk of retinal damage that would otherwise result from repeated retinal punctures.

[0138] like Figure 15A As shown, the delivery system 1500 typically includes an injection needle 1512, a single-lumen or multi-lumen conduit 1520, a stabilizer 1560, and a fluid drive system 1570. The injection needle 1512 has a proximal end 1504 and a distal end 1506. In some embodiments, the injection needle 1512 further includes a connection device 1518 (described in more detail below) at its proximal end 1504, which facilitates connection of the injection needle 1512 to the conduit 1520. The conduit 1520 has a distal end 1522 attached to the proximal end 1504 of the injection needle 1512 via the connection device 1518, and a proximal end 1524 attached to the fluid drive system 1570 (e.g., via a handle, as discussed below).

[0139] Figure 15B It is along Figure 15A An enlarged cross-sectional view taken by section lines 15B-15B shows an exemplary conduit 1520 with multiple lumens, which is also used in conjunction with other delivery devices and systems described herein. The multi-lumen conduit 1520 includes an outer wall 1526o surrounding three lumens 1528a, 1528b, and 1528c. Although Figure 15B Three lumens are shown, but more or fewer lumens may be used (e.g., two or more lumens, two to four lumens, two lumens, or four lumens). Lumens 1528a-c are separated by an inner wall 1526i that intersects with the outer wall 1526o. Lumens 1528a-c radially surround the central longitudinal axis 1520x of the pipe 1520. Figure 15B In the embodiments, one or more of the lumens 1528a-c have different sizes. For example, each of the lumens 1528a, 1528b extends one-quarter of the way around the multi-lumen conduit 1520 in the circumferential direction. On the other hand, lumen 1528c extends half the way around the conduit 1520 in the circumferential direction. Therefore, in Figure 15BIn one embodiment, the volume of lumen 1528c can be twice the volume of each of lumens 1528a and 1528b. In some other embodiments, each of lumens 1528a-c has the same size.

[0140] Now return to Figure 15A The fluid drive system 1570 may include a fluid pump 1572 for driving flow through the conduit 1520. In some embodiments, the fluid pump may include an injection pump, a vernier flow control (VFC) pump, or another type of pressure control pump, volume control pump, variable volume control pump, peristaltic pump, lever-actuated pump, valve-actuated pump, or venturi pump. The fluid drive system 1570 further includes one or more fluid reservoirs 1574 for storing one or more injectable fluids. Although Figure 15A Three fluid reservoirs 1574 are shown, but more or fewer fluid reservoirs may be used. In some embodiments, each of the fluid reservoirs 1574 may be configured to be actuated by a fluid pump 1572 to drive the flow of fluid stored therein. Such fluids may include injectable fluids, including: non-therapeutic solutions, such as ophthalmic irrigation solutions having physiological pH (acidity / alkalinity) and osmotic pressure (e.g., BSS); and therapeutic solutions, such as therapeutic substances for treating the eye (e.g., anti-VEGF (vascular endothelial growth factor)), tissue plasminogen activator (tPA), stem cells, viral vectors for gene therapy, other drugs, or combinations thereof). The fluids may also include working fluids, such as fluids for extending the stabilizer 1560 (e.g., perfluorocarbon liquid (PFCL), BSS, saline, air, N2 (nitrogen), other liquids or gases, or combinations thereof).

[0141] The fluid drive system 1570 further includes a controller 1576 for controlling the operation of the fluid pump 1572. In some embodiments, the controller 1576 includes a wireless receiver that wirelessly receives instructions from a console (e.g., surgical console 402). In some other embodiments, the controller 1576 communicates with the console via a wired connection.

[0142] Figure 15C yes Figure 15A A top isometric view of a portion of the delivery system 1500. As shown, the connecting device 1518 has one or more ports 1519 corresponding to the one or more lumens of the conduit 1520. Figure 15C The example shows three ports 1519a, 1519b, and 1519c, each corresponding to... Figure 15BThe distal ends of the lumens 1528a-c of the multi-lumen conduit 1520 are disposed within these distal ends. Two separate ports 1519a, 1519b of the connecting device 1518 are joined together toward the distal end 1506 of the injection needle 1512. Port 1519c, on the other hand, is separate from and fluidly isolated from each of ports 1519a, 1519b. Port 1519c is fluidly coupled to stabilizer 1560, as shown, to facilitate its extension.

[0143] refer to Figure 15A and Figure 15C In the diagram, stabilizer 1560 is shown in an extended position, in which stabilizer 1560 extends from port 1519c of connector 1518. In some embodiments, stabilizer 1560 and port 1519c are oriented such that stabilizer 1560 extends distally from the distal end of connector 1518, as shown in the diagram. Figure 15C As shown in the diagram. In some embodiments, stabilizer 1560 and port 1519c are oriented such that stabilizer 1560 extends laterally through external port 1564 in the sidewall of connector 1518. In the extended position, stabilizer 1560 stabilizes / secures the injection needle 1512 at the target injection site (i.e., location) on the retinal surface for subretinal injection, which reduces the likelihood of the injection needle 1512 being unintentionally removed from the subretinal space during the procedure due to minor forces. Stabilization further controls the injection position. Figure 15A and Figure 15C In the example, stabilizer 1560 is a balloon 1562 or a bag. The balloon 1562 can have any suitable shape, including but not limited to circular, oval, or polygonal. The balloon 1562 can be formed of plastic, metal, polymer, nitinol, or a combination thereof.

[0144] Before the stabilizer 1560 is in the extended position, the stabilizer 1560 is disposed within port 1519c of the connecting device 1518. In some embodiments, to actuate the stabilizer 1560 to the extended position, working fluid (e.g., PFCL) is injected from one of the fluid reservoirs 1574 of the fluid drive system 1570 through a lumen (e.g., lumen 1528c) to fill the balloon 1562. In some embodiments, the balloon 1562, and therefore the injection needle 1512, is held in place primarily by the weight of the working fluid in the balloon 1562.

[0145] In another embodiment, the injection needle 1512 and stabilizer 1560 are held in place by magnetic force. For example, the injection needle 1512 may include a magnetic material. Using a magnetic material for the injection needle 1512 and combining it with one or more electromagnetic coils or magnets 1550 positioned around the patient's head in a desired location during a subretinal procedure can improve the stability of the injection needle 1512 and stabilizer 1560. For example, the one or more electromagnetic coils or magnets 1550 can generate a one-dimensional magnetic field to apply a downward force toward the retina on the magnetic injection needle 1512, a force separate from any gravitational force on the injection needle 1512.

[0146] When using electromagnetic coil 1550, it can include any suitable electromagnetic coil configured to generate a magnetic field when a current is applied through it. Typically, the direction of the generated magnetic field will be perpendicular to the circular surface of the coil and can be reversed by changing the direction of the current through it. To modify the strength of the generated magnetic field, the current applied to electromagnetic coil 1550 can be increased or decreased. The number and location of electromagnetic coils 1550 can vary depending on the desired positioning of injection needle 1512 in the patient's eye. In some embodiments, electromagnetic coil 1550 can be integrated into a patient head support, patient worktable, or any suitable device positioned behind the patient's head during a subretinal injection procedure. As described above, magnet 1550 can be used alternatively to electromagnetic coil 1550.

[0147] In yet another embodiment, the injection needle 1512 and stabilizer 1560 are held in place by negative pressure. For example, in some embodiments, the connecting device 1518 may include a port 1552 at its distal end. In such an embodiment, the port 1552 is fluidly connected via at least one lumen of the conduit 1520 to a vacuum source at the proximal end of the conduit 1520 to generate negative pressure or vacuum suction through the port 1552. Thus, after the injection needle 1512 is positioned at the target injection site on the retinal surface for subretinal injection, the vacuum source can be activated to generate a vacuum suction acting on the retinal surface through the port 1552, thereby fixing the injection needle 1512 and stabilizer 1560 against the retina. Typically, the negative pressure generated by the vacuum source is small enough that it will not cause any damage to the retina, but large enough to stabilize the injection needle 1512 against the retina.

[0148] Figure 15D According to the embodiments in this article Figure 15A A schematic diagram of a delivery system 1500, showing an exemplary underretinal delivery device 1501 combined with it. Meanwhile, Figure 15E yes Figure 15DA partial enlarged side cross-sectional view showing the injection needle 1512 used in conjunction with the delivery system 1500 described herein. Therefore, for clarity, it is described here together. Figures 15D to 15E .

[0149] In general, the delivery device 1501 is substantially similar to other subretinal delivery devices described herein, but device 1501 is configured to be releasably coupled to the injection needle 1512 and the conduit 1520 after the injection needle 1512 has been inserted into the subretinal cavity. Delivery device 1501 includes a tubular injection cannula 1510 that directly engages the injection needle 1512 and is insertable into the eye. The injection cannula 1510 has an internal channel that extends longitudinally from its proximal end 1516 to its distal end 1514, thereby surrounding the conduit 1520.

[0150] The injection cannula 1510 extends from a handheld component 1502, which is configured to be grasped and manipulated by a surgeon or surgical assistant. The handheld component 1502 includes a needle release actuation mechanism 1540 for releasing the needle 1512 from the injection cannula 1510 when the needle 1512 is properly positioned and secured within the eye. It is contemplated that the release actuation mechanism 1540 may include any suitable type of mechanical mechanism for releasing the needle 1512. For example, in some embodiments, the release actuation mechanism 1540 may include a sliding button or switch that moves the release mechanism to disengage the injection cannula 1510 from the connecting device 1518, thereby allowing the injection cannula 1510 to retract away from the needle 1512.

[0151] In some embodiments, the injection cannula 1510 has a slit extending from its proximal end 1516 to its distal end 1514, thus forming a U-shape in the top section. In such an embodiment, the delivery device 1501 is configured to disconnect from the external eye cannula 1520 by sliding the conduit 1520 through the slit.

[0152] exist Figure 15D and Figure 15E In this embodiment, the delivery device 1501 is shown in a configuration ready to begin a subretinal injection procedure. For example, the delivery device 1501 is coupled to an injection needle 1512, and the injection cannula 1510 of the delivery device 1501 surrounds the tubing 1520. Furthermore, the stabilizer 1560 is in a retracted position disposed within the port 1519c of a connecting device 1518, which is located within the distal end 1514 of the injection cannula 1510. In some embodiments, such as... Figure 15EAs shown, the injection cannula 1510 of the delivery device 1501 extends beyond the distal end 1522 of the conduit 1520 and surrounds the connector 1518 of the injection needle 1512. In some embodiments, the injection cannula 1510 has an inner diameter corresponding to the outer diameter of the connector 1518. In some embodiments, the inner diameter of the injection cannula 1510 is between about 0.35 mm and about 0.65 mm, for example, between about 0.45 mm and about 0.55 mm, while the outer diameter of the connector 1518 is between about 0.4 mm and about 0.7 mm, for example, between about 0.5 mm and about 0.6 mm. However, other sizes are also contemplated.

[0153] Figure 15F A top-down isometric view of a portion of a delivery system 1500, featuring an alternative design for the injection needle 1582 and stabilizer 1590. Figure 15F In one embodiment, the stabilizer 1590 is positioned outside the needle 1582 in both the retracted and extended positions.

[0154] As shown in the figure, the injection needle 1582 has a proximal end 1584 and a distal end 1586. In some embodiments, the injection needle 1582 further includes a connecting device 1588, which extends distally from the proximal end 1584 by a length C less than the total longitudinal length N of the injection needle 1582. In some embodiments, the connecting device 1588 can facilitate connection of the injection needle 1582 to the single-lumen or multi-lumen conduit 1520 described above. For example, the distal end 1522 of the conduit 1520 can be attached to the proximal end 1584 of the injection needle 1582 via the connecting device 1588, while the proximal end 1524 is attached to a fluid drive system (e.g., via a handle, as discussed below).

[0155] Similar to connector 1518, connector 1588 has one or more internal ports 1578 corresponding to the one or more lumens of conduit 1520. Figure 15F The example shows two ports, 1578a and 1578b, each corresponding to... Figure 15B The lumens 1528a and 1528b of the multi-lumen conduit 1520 are configured to be fluidly connected to their distal ends. The two separate ports 1578a and 1578b of the connecting device 1588 are joined together toward the distal end 1586 of the injection needle 1582.

[0156] The stabilizer 1590 includes a plurality of flexible, bendable legs 1592, which, in some embodiments, can be oriented such that they extend along the main longitudinal axis A of the injection needle 1582 when in an "inactive" position. Figure 15FIn the diagram, three legs 1592 are shown in the "active" position, providing a three-point stabilization mechanism for securing the injection needle 1582 to the target injection site on the retinal surface; however, it is contemplated to utilize more legs 1592, such as four, five, six, or more. Each of these multiple legs 1592 is proximally coupled to a movable extension ring 1594 externally connected to a connecting device 1588 and distally coupled to a fixed base 1596 adjacent to the distal end 1586 of the injection needle 1582. In some embodiments, the length of the injection needle 1582 extending distally from the base 1582 is equal to or substantially equal to the thickness of the retina to allow traversal into the subretinal space during injection. The legs 1592 are formed of any suitable flexible material to facilitate bending, including flexible metals such as nitinol and other metal alloys, and flexible thermoplastic polymers such as polyimide.

[0157] Similarly, stabilizer 1590 is shown in the active position, in which the legs 1592 of stabilizer 1590 are bent and the central portion 1583 of each leg 1592 extends laterally outward from the connecting device 1588. As described above, in some embodiments, when in the inactive position, the legs 1592 may extend substantially parallel to the main longitudinal axis A of the injection needle 1582. To change stabilizer 1590 from this inactive position to the active position, an extension ring 1594 may be actuated in the distal direction 1554 (towards the distal end 1586 of the injection needle 1582), which may be longitudinally movable along the length C of the connecting device 1588. The distal movement of the extension ring 1594 causes the legs 1592 to flex or bend laterally outward from the connecting device 1588, as the connecting device 1588 prevents them from bending inward. Thus, a suitable three-point support is created for stabilizing the injection needle 1582 during injection. To return the stabilizer 1590 to the inactive position, the extension ring 1594 can be actuated in the proximal direction 1556, causing the outrigger 1592 to extend longitudinally and thus straighten. In some embodiments, the extension ring 1594 may be locked in an inactive position and an active position, and / or locked in one or more progressively increasing positions in between.

[0158] Typically, to actuate the extension ring 1594 in the distal direction 1554 and change the outrigger 1592 from the inactive position to the active position, a push rod or other suitable mechanism on the delivery device's injection cannula can be used. For example, before disconnecting the injection needle 1582 from the delivery device's injection cannula (see below). Figure 16CAs discussed, the user can actuate a toggle on the delivery device handle to move a plunger or other feature on the injection cannula distally, which in turn can act on the extension ring 1594 and cause the extension ring 1594 to translate distally. The plunger can engage with the extension ring 1594 via any suitable means, such as a hook or clamp. In some embodiments, the plunger can be detachably engaged with the extension ring 1594.

[0159] In some embodiments, to secure the extension ring 1594 in the active position, the extension ring 1594 can be rotated over a pin or other locking mechanism in a first rotational direction. In such embodiments, to facilitate the transition of the extension ring 1594 back to the inactive position, the extension ring 1594 can be rotated in a second rotational direction opposite to the first rotational direction to unlock the extension ring 1594 from the pin or other locking mechanism. In some embodiments, the outer diameter of the connecting device 1588 can gradually increase in the distal direction, thus allowing the extension ring 1594 to be secured to the connecting device 1588 via mechanical friction. In some embodiments, when transitioning from the active to the inactive position, the elasticity of the leg 1592 allows the leg 1592 and therefore the extension ring 1594 to "spring" back to the elongated inactive position.

[0160] In some embodiments, the extension ring 1594 is permanently fixed along the connecting device 1588 in a longitudinal position that causes the outrigger 1592 to be continuously flexed or bent, but it can be configured to rotate about the connecting device 1588 to decrease or increase the width of the stabilizer 1590, thereby changing the stabilizer from an inactive or active position, respectively. In such an embodiment, to change the stabilizer 1590 to the inactive position, the extension ring 1594 can be rotated in a first rotation direction 1546 so that the outrigger 1592 is coiled around the connecting device 1588. To change the stabilizer 1590 to the active position, the extension ring 1594 can be rotated in a second rotation direction 1548 opposite to the first rotation direction 1546. This rotation of the extension ring 1594 can be accomplished via any suitable rotation mechanism, such as on the injection cannula of a delivery device. In such embodiments, before the injection needle 1582 is released from the injection cannula 1510 to perform a subretinal injection, the extension ring 1594 can be rotated to reposition the leg 1592 to the active position. Then, after the subretinal injection is performed and the injection cannula 1510 is reattached to the injection needle 1582, the extension ring can be rotated again to reposition the leg 1592 to the inactive position, allowing for removal from the eye. However, in some embodiments, the injection needle 1582 can be retracted after injection without reattaching the injection cannula 1510, and the leg can spring back to the inactive position due to its elasticity when, for example, a trocar or other access cannula comes into contact with the leg 1592 during removal from the eye.

[0161] In yet another embodiment, instead of using a push rod or other mechanical feature to actuate the extension ring 1594 and bend the legs 1592, pressurized fluid can be used to fill or inflate the legs 1592, causing them to extend laterally from the connecting device 1588. This pressurized fluid can be contained within one or more flexible membranes disposed between the legs 1592.

[0162] In another embodiment, the injection needle 1582 and stabilizer 1590 may also be held in place by magnetic force and / or negative pressure, as described above with reference to the injection needle 1582. For example, in some embodiments, the injection needle 1582 may include a magnetic material configured to be acted upon by a magnetic force applied thereon. In some embodiments, the injection needle 1582 may include a port through the distal surface of the base 1596, which may be fluidly coupled to a vacuum source at the proximal end of the conduit 1520 via at least one lumen of the conduit 1520 to generate negative pressure or vacuum suction through the port.

[0163] Figures 16A to 16E Demonstrates the use of certain embodiments Figures 15A to 15EA cross-sectional view of the delivery system with stabilizer 1560 performing different steps of subretinal injection at eye 1600. Although stabilizer 1560 has been described and shown, Figures 16A to 16E The operations in this context can also be performed using other stable mechanisms, including... Figure 15F The stabilizer in the middle is 1580.

[0164] Turn now Figure 16A In preparation for subretinal injection, a scleral cannula 1602 is used to cut the sclera. This scleral cannula consists of a valved insertion cannula 1632 and a scleral needle, as described above. Figure 2 The cannula is removed from the eye 1600, leaving the valved insertion cannula 1632 in place. The injection cannula 1510 of the delivery device 1501 is then inserted into the eye 1600 via the valved insertion cannula 1632, and the distal end 1506 of the injection needle 1512 is guided through the vitreous cavity 1612 and inserted into the subretinal cavity 1624 at the target injection site on the surface of the retina 1604.

[0165] After that, Figure 16B At the target injection site on the surface of the retina 1604, the injection needle 1512 is secured to the surface of the retina 1604 using a stabilizer 1560. In some embodiments, pressure or fluid is applied through a lumen (e.g., lumen 1528c) of the conduit 1520 to extend the stabilizer 1560 from the connector 1518, thereby positioning the stabilizer 1560 in contact with the surface of the retina 1604. The stabilizer 1560 is configured to securely contact the retina 1604 in such a way that the injection needle 1512 is secured to the target injection site on the surface of the retina 1604. In some embodiments, the stabilizer 1560 is formed of a material that conforms to the surface of the retina 1604 to increase the contact area between the two.

[0166] In embodiments where magnetic force is used to stabilize the injection needle 1512, an effective magnetic field (e.g., via a coil or magnet) can be provided to act on and fix the injection needle 1512. In embodiments where negative pressure is used to stabilize the injection needle 1512, a vacuum source can be activated to supply vacuum suction at, for example, port 1552.

[0167] exist Figure 16CAt the point where the stabilizer 1560 contacts the surface of the retina 1604, the injection cannula 1510 of the delivery device 1501 is retracted from the eye 1600. Upon retraction of the injection cannula 1510, the injection needle 1512 and the tubing 1520 are disconnected by external force. As used herein, external force generally includes any force applied from outside the eye 1600 to the injection needle 1512 or the tubing 1520. For example, external force generally includes slight and / or unintentional movement of any part of the delivery system 1500 or delivery device 1501 by a surgeon or surgical assistant. In some embodiments, disconnection limits the effect of external forces associated with injection and / or movement of a handheld instrument, such as the delivery device 1501. In some embodiments, an excessively long tubing 1520 is provided inside the eye 1600 in an unrestrained state to facilitate disconnection. It will be understood that when an external force is applied to the conduit 1520, the excessive length allows the conduit 1520 to move inside the eye 1600 without transmitting force to the injection needle 1512.

[0168] exist Figure 16D At the site, an injection fluid (e.g., a non-therapeutic solution and / or a therapeutic solution) is injected from the fluid drive system 1570 into the subretinal cavity 1624 via one or more lumens of the conduit 1520.

[0169] In some embodiments, the injection fluid is administered in a one-step procedure, which can greatly simplify the fluid manipulation of the injection fluid and the overall injection procedure. For example, the fluid drive system 1570 may include a fluid reservoir 1574 storing a mixture of both the therapeutic solution and the non-therapeutic solution (referred to herein as a “premixed” solution). Thus, a fluid pump 1572 may drive the premixed solution through a single lumen of conduit 1520 to inject the premixed solution into the subretinal space 1624 in a single step. Because the therapeutic and non-therapeutic solutions are premixed, this one-step approach can be used to deliver precise doses of therapeutic material.

[0170] like Figure 16D As shown, in some embodiments, the injected premixed solution forms a bubble 1634 in the subretinal space 1624 between the retina 1604 and the retinal pigment epithelium (RPE) 1630, which is a local hemispherical elevation of the retina 1604. Because the fluid injected in one step includes both the premixed therapeutic and non-therapeutic solutions, the dispersion of the injected fluid within the bubble 1634 can be more uniform.

[0171] In some other embodiments, the injection fluid is administered in a two-step procedure, wherein the non-therapeutic solution and the therapeutic solution are injected separately without premixing. For example, the non-therapeutic solution may first be injected from the fluid drive system 1570 into the subretinal space 1624 via one lumen of the multi-lumen conduit 1520 (e.g., lumen 1528b). This first step may form an initial blister 1634 in the subretinal space 1624. Subsequently, the therapeutic solution may then be injected from the fluid drive system 1570 into the subretinal space 1624 via another lumen of the multi-lumen conduit 1520 (e.g., lumen 1528a), thereby causing the blister 1634 to expand from its initial size. Utilizing this two-step procedure may be particularly advantageous for clinical studies where the ideal or preferred concentration of the therapeutic substance has not yet been determined, as the therapeutic substance can be injected gradually and separately from the non-therapeutic solution, thus providing greater dosing flexibility.

[0172] In some embodiments, the injection of the premixed solution, or each of the non-therapeutic and therapeutic solutions, is performed manually. For example, fluid pump 1572 can drive the flow of each of the premixed solution, non-therapeutic solution, therapeutic solution, and / or working fluid without manually actuating the plurality of fluid reservoirs 1574. In some embodiments, fluid pump 1572 operates according to instructions received from controller 1576. In some embodiments, controller 1576 receives control signals via a wireless receiver. In some embodiments, the surgeon or surgical assistant can use a foot pedal (e.g., foot pedal 410) to control the injection pressure or volume of each fluid, which wirelessly communicates with controller 1576 via a wireless receiver and / or antenna.

[0173] exist Figure 16E After the injection of the injection fluid is completed, the injection needle 1512 can be released from fixation by retracting the stabilizer 1560 into the connecting device 1518, thereby removing the stabilizer 1560 from contact with the surface of the retina 1604. In some embodiments, vacuum pressure is used to remove the working fluid from the stabilizer 1560 and / or the corresponding lumen, causing the stabilizer 1560 to retract therein. In some embodiments, the stabilizer 1560 is removed from contact with the retina 1604 without retracting into the connecting device 1518. In embodiments where magnetic force is used to stabilize the injection needle 1512, the magnetic field acting on the injection needle 1512 can be suppressed or disabled. In embodiments where negative pressure is used to stabilize the injection needle 1512, the vacuum source supplying negative pressure at, for example, port 1552 can be disabled.

[0174] Subsequently, the conduit 1520 and the injection needle 1512 attached to the conduit can be removed from the eye 1600. In some embodiments, the injection site may remain patch-free. In some other embodiments, the injection site may be filled with a sealant (e.g., fibrin glue, collagen, cyanoacrylate, cell adhesion factor, fibronectin, laminin, extracellular matrix-based hydrogel, polyacrylic acid, zinc polycarboxylate adhesive, silicone adhesive, or ophthalmic adhesive surgical device (OVD) or viscoelastic insert).

[0175] Figures 17A to 17C A side cross-sectional view of an exemplary subretinal delivery device 1700 according to certain embodiments of this disclosure is shown. This device is configured for use in conjunction with an optical coherence tomography (OCT) system to provide OCT guidance during a subretinal injection procedure. The delivery device 1700 can be used as, for example... Figure 4 The delivery device 414 of the surgical system 400 or other surgical systems for subretinal injection as described herein. Furthermore, aspects of the delivery device 1700 can be combined with other delivery devices and / or components described herein without limitation.

[0176] Subretinal injections are typically very delicate procedures because they require piercing one or more tissues / membranes of the eye to access the subretinal space, and therefore, such procedures demand highly skilled surgeons to minimize trauma. To assist surgeons and improve procedure safety during such procedures, OCT-based guidance can be used. OCT is an imaging technique that uses low-coherence light to capture real-time, micrometer-resolution one-dimensional, two-dimensional, and three-dimensional (e.g., cross-sectional) images from within biological tissues. During ophthalmic procedures such as subretinal injections, OCT can be used to: determine the overall structure of ocular tissues or layers; measure the distance from the probe tip to the ocular tissues or layers; and / or measure the thickness of ocular tissues or layers, etc. Therefore, when used during subretinal injections, OCT can assist surgeons in accurately placing the delivery device, injection cannula, and / or injection needle inside the eye for injection.

[0177] Turn now Figure 17A and Figure 17BThe delivery device 1700 includes a handle 1702 and a tubular injection cannula 1710, wherein a proximal end 1716 of the injection cannula 1710 is coupled to a distal end 1704 of the handle 1702 and extends distally from the distal end of the handle. Extending from the distal end 1714 of the injection cannula 1710 is an inner fluid shaft 1760, and within the inner fluid shaft 1760 is a curved or substantially straight injection needle 1712 (a straight injection needle 1712 is shown). The injection needle 1712 is fixedly coupled to and extends distally from the distal end of the inner fluid shaft 1760, the diameter of which may be larger than the diameter of the injection needle 1712. Therefore, in such an embodiment, the distal end 1762 of the inner fluid shaft 1760 may be externally coupled to the injection needle 1712 for a given length of the proximal end 1706 of the injection needle 1712.

[0178] The internal fluid shaft 1760 is configured to slidably extend from and retract into the distal end 1714 of the injection cannula 1710 by actuation of an actuator 1740 (which may be a sliding actuator) on the handle 1702. Figure 17A and Figure 17B In one embodiment, the proximal end 1764 of the inner fluid shaft 1760 is fluidly coupled to a slider 1770 (or the base of an actuator 1740), which is disposed through the inner cavity 1772 of the handle 1702 and connected to the actuator 1740. Actuation (here, sliding) of the actuator 1740 causes the slider 1770 to translate within the handle 1702 and along the main longitudinal axis A of the handle 1702 and the injection cannula 1710. Accordingly, translation of the actuator 1740 in a first distal direction (as indicated by arrow 1774) allows the slider 1770 to translate distally within the cavity 1772, thereby causing the inner fluid shaft 1760 and the injection needle 1712 coupled to the inner fluid shaft to extend out of the injection cannula 1710. In the fully extended position, at least a portion of both the inner fluid shaft 1760 and the injection needle 1712 is exposed from the injection cannula 1710. Simultaneously, the translation of the actuating element 1740 in the second proximal direction (as shown by arrow 1776) allows the sliding element 1770 to translate proximally within the cavity 1772, thereby retracting the internal fluid shaft 1760 and the injection needle 1712 connected to the internal fluid shaft into the injection cannula 1710. It should be noted that... Figure 17A and Figure 17B The actuation mechanism described is merely exemplary, and other actuation mechanisms for translating the slider 1770, such as deformable baskets, buttons, etc., are also envisioned.

[0179] A flexible fluid conduit 1720 for supplying injection fluid (e.g., non-therapeutic and / or therapeutic solutions) to the delivery device 1700 is disposed through the proximal end 1706 of the handle 1702 and fluidly coupled to a slider 1770 within the handle 1702. The flexible fluid conduit 1720, slider 1770, inner fluid shaft 1760, and injection needle 1712 form a single, continuous channel for supplying fluid flow during subretinal injection.

[0180] same, Figures 17A to 17C The delivery device 1700 is configured for use in conjunction with an OCT system to provide OCT-based guidance during subretinal injection procedures. To enable OCT imaging during subretinal fluid delivery, an optical fiber 1780 is positioned to pass through the proximal end 1706 of the handle 1702, through the cavity 1772 and the injection cannula 1710, and terminate distally at the internal fluid axis 1760 (see [link to original document]). Figure 17C (Enlarged view). In some embodiments, such as Figure 17A and Figure 17B In the example, the optical fiber 1780 may extend within the cavity 1772 through the base of the slider 1770 or the actuator.

[0181] Fiber optic cable 1780 is connected to OCT system 1782, which may include any suitable type of OCT device, such as a time-domain or frequency-domain OCT device, a Fourier transform OCT device, etc., to provide real-time short-range or long-range one-dimensional (e.g., from the center point), two-dimensional, and / or three-dimensional images of the anatomical structures within the patient's eye. This OCT imaging can then be used to determine measurements of various individual or aggregate physical parameters of the patient's eye, including the shape and thickness of various membranes. Additionally, OCT imaging can be used during ophthalmic procedures to determine the distances and / or positions of the distal tip 1711 or internal fluid axis 1760 of the injection needle 1712 and the distal ends 1762 and 1714 of the injection cannula 1710 relative to ocular tissues (e.g., the retina). Accordingly, the surgeon can use visualization from OCT system 1782 during subretinal injection procedures to guide the placement of the injection needle 1712 (e.g., between the sensory retina and the RPE) without causing any unnecessary damage to surrounding tissues, thereby improving the safety and ease of the procedure.

[0182] Turn now Figure 17CThe image shows the injection needle 1712, the internal fluid shaft 1760, and the distal ends 1762 and 1714 of the injection cannula 1710. In this example, the optical fiber 1780 is disposed through a hole 1766 in the cylindrical wall of the internal fluid shaft 1760 and terminates at its distal end 1762. In some other embodiments, the optical fiber 1780 may be fixedly attached, for example, by an adhesive to a groove in the outer surface of the wall of the internal fluid shaft 1760, and may terminate at any point along the length of the internal fluid shaft 1760. Because the internal fluid shaft 1760 is fixedly attached to the injection needle 1712 and translates therewith, the distance between the distal termination of the optical fiber 1780 and the distal end 1711 of the injection needle 1712 remains constant during use, thereby enabling continuous and accurate OCT measurements of the distance between the distal end 1711 and the ocular tissue during the administration of a subretinal injection procedure.

[0183] Figure 18A and Figure 18B Perspective views of exemplary subretinal delivery devices 1800 and 1801 according to certain embodiments of this disclosure are shown. Delivery devices 1800 and 1801 can be used as, for example... Figure 4 The delivery device 414 of the surgical system 400, and its aspects can be combined with other delivery devices and / or components described herein without limitation. Certain aspects of delivery devices 1800 and 1801 are as referenced above. Figure 3 The described subretinal injection (and other related procedures) performed via the suprachoroidal route is particularly beneficial.

[0184] Turn now Figure 18A The delivery device 1800 includes a handle 1802 and a tubular injection cannula 1810 having a proximal end 1816 coupled to and extending distally from the distal end of the handle 1802. The distal end 1814 of the injection cannula 1810 includes a distal tip 1811, which in some embodiments may taper or be angled relative to the main longitudinal axis of the injection cannula 1810 to facilitate separation of the choroid from the sclera as the injection cannula 1810 moves through the suprachoroidal space. In some embodiments, the distal tip 1811 may have an oval, broadened, or flat cross-section to facilitate easier translation through the suprachoroidal space. Exemplary distal tips are discussed in more detail below. The injection cannula 1810 and / or the distal tip 1811 are typically formed of any suitable flexible surgical-grade material, such as a metallic material or a thermoplastic polymer material. Examples of flexible metallic materials include nitinol and other metal alloys. Examples of suitable thermoplastic polymer materials include polyimide. In some embodiments, the distal end 1811 is formed of a rigid material, and the remainder of the injection cannula 1810 is formed of a flexible material.

[0185] In some embodiments, the distal tip 1811 may include a magnetic material. Utilizing a magnetic material for the distal tip 1811, in conjunction with one or more electromagnetic coils 1880 positioned around the patient's eye at a desired location, can improve the maneuverability of the injection cannula 1810 and the distal tip 1811 within the suprachoroidal space for subretinal injection. For example, the one or more electromagnetic coils 1880 may be activated to generate a one-dimensional, two-dimensional, or three-dimensional magnetic field and apply a force to the magnetic distal tip 1811 to steer it within the suprachoroidal space, a force separate from any force applied by the user to the delivery device 1800 to move the distal tip 1811 "forward" through the suprachoroidal space (e.g., away from the entry point into the eye, or "scleral incision"). This magnetic orientation of the distal tip 1811 facilitates easier and more precise manipulation and controllability of both the distal tip 1811 and the injection cannula 1810 as they are moved and / or positioned within the suprachoroidal space for subretinal injection. In some respects, the magnetic orientation also allows for improved ergonomics during the insertion procedure, as the physical burden on the surgeon in correctly positioning and manipulating the distal tip 1811 within the suprachoroidal space is reduced.

[0186] In embodiments where one or more electromagnetic coils 1880 are used to generate a one-dimensional magnetic field, a one-dimensional force can be applied to the magnetic distal end 1811 to steer it in a first lateral direction and a second lateral direction opposite to the first direction, a force separate from any force that pushes the distal end 1811 forward. In such embodiments, the first and second lateral directions are each perpendicular to the main longitudinal axis A of the injection cannula 1810 along its longitudinal length and are also tangential to the suprachoroidal lumen. Furthermore, the one-dimensional force may not be strong enough on its own to push or pull the distal end 1811; instead, it can be limited so that it only assists in steer the distal end 1811, and any actual movement of the distal end 1811 is caused by a user manually applying force to the handle 1802.

[0187] In embodiments that utilize two or more electromagnetic coils 1880 to generate a two-dimensional or three-dimensional magnetic field, a two-dimensional or three-dimensional force can be applied to the magnetic distal end 1811 to steer it in one or more directions in addition to a first lateral direction and a second lateral direction. In such embodiments, the magnetic distal end 1811 (and therefore the injection cannula 1810) can be moved through the suprachoroidal lumen without any force applied by the user to the handle 1802—instead, the distal end 1811 and the injection cannula 1810 can be fully controlled and positioned by applying and modifying the two-dimensional or three-dimensional magnetic field acting on the distal end 1811.

[0188] Typically, the electromagnetic coil 1880 may include any suitable electromagnetic coil configured to generate a magnetic field when a current is applied through the coil. Typically, the direction of the generated magnetic field will be perpendicular to the circular surface of the electromagnetic coil and can be reversed by changing the direction of the current through the coil. To modify the strength of the generated magnetic field, the current applied to the electromagnetic coil 1880 can be increased or decreased. The number and position of the electromagnetic coils 1880 can vary depending on the desired insertion orientation of the distal end 1811 and the positioning of the patient's eyes. In some embodiments, the electromagnetic coils 1880 may be integrated into a patient head support and / or a worktable or operating table. For example, in the case of integration into a head support, one coil may be placed in the head support above the patient's head, one coil may be placed in the head support behind the patient's head, and another coil may be placed in the head support on either side of the patient's head.

[0189] In some embodiments, at least a portion of the distal end 1814 of the injection cannula 1810 (e.g., the distal tip 1811) comprises a photoluminescent material, such as a phosphorescent material. For example, in some embodiments, the distal tip 1811 of the injection cannula 1810 may comprise a material containing a phosphor, thereby emitting visible light after being excited by, for example, visible light. The use of a photoluminescent material on the distal tip 1811 (or other portions of the distal end 1814) allows the location of the distal tip to be seen through the choroid and retina via a microscope or other observation system having a viewing angle through the lens or sclera pointing towards the retina as the injection cannula 1810 moves through the suprachoroidal space. For example, the distal tip 1811 may be exposed to a visible light source for an appropriate amount of time to excite the photoluminescent material before the injection cannula 1810 is inserted into the patient's eye during a procedure. Subsequently, as the injection cannula 1810 is inserted and moved through the suprachoroidal space, the distal tip 1811 will continuously emit light that can be seen through the choroid and retina by a microscope or other observation system. This visibility of the position of the distal tip 1811, or other parts of the distal tip 1814, facilitates efficient positioning of the injection cannula 1810 for subretinal injection at the target injection site.

[0190] In some embodiments, the injection cannula 1810 includes an optical fiber 1882 (dashed line) having a distal end 1884 terminating at or near a distal tip 1811 and configured to emit light from the distal tip. The optical fiber 1882 may extend proximally through the injection cannula 1810, through the handle 1802, and be optically coupled to any suitable visible light source, such as a white light source, either inside or outside the handle. For example, the optical fiber 1882 may be optically coupled to a light source integrated with a surgical console. During a subretinal injection procedure, as the injection cannula 1810 is inserted into and moved through the suprachoroidal space, the light source can be activated by the surgeon to emit visible light from the distal end 1884 of the optical fiber 1882. This visible light can be seen through the choroid and retina using a microscope or other observation system with a viewing angle pointing towards the retina through the lens or sclera. Accordingly, the light emitted from optical fiber 1882 can be used to guide the positioning of the distal end 1814 of injection cannula 1810, so as to efficiently and accurately place the distal end near the target injection site during a subretinal injection procedure. In some embodiments, optical fiber 1882 comprises a single-core optical fiber; in other embodiments, optical fiber 1882 comprises a multi-core optical fiber. Typically, one or more claddings may be external to or surround one or more cores of optical fiber 1882.

[0191] like Figure 18A As further shown, a curved or straight injection needle 1812 (a curved needle is shown) is disposed within the injection cannula 1810 for piercing the desired ocular tissue (here, the choroid and RPE) at an angle relative to the main longitudinal axis of the injection cannula 1810 to deliver fluid into the subretinal space. In an exemplary embodiment, the injection cannula 1810 is a 23, 25, or 27 gauge needle, while the injection needle 1812 is a finer gauge needle, such as a 38 gauge needle. However, in other embodiments, other sizes / gauges of injection cannulas and injection needles may be used. In some embodiments, the injection needle 1812 is formed of a material similar to that of the injection cannula 1810 and / or the distal tip 1811.

[0192] In some embodiments, the injection needle 1812 is configured to slidably extend from and retract into the distal end 1814 of the injection cannula 1810, which helps prevent damage to the injection needle 1812 during insertion of the injection cannula 1810 into and / or movement within the eye. This actuation of the injection needle 1812 can be controlled by any suitable mechanism. Figure 18AIn the example, actuation of the injection needle 1812 is controlled by a toggle 1840 of the handle 1802. In some embodiments, the toggle 1840 includes a sliding button or switch, wherein a user (e.g., a surgeon) slides the toggle 1840 in a distal direction 1842 to extend the injection needle 1812 out of the injection cannula 1810, and slides the toggle 1840 in a proximal direction 1844 to retract the injection needle 1812 back into the injection cannula 1810.

[0193] In some embodiments, the sliding toggle 1840 may also be lockable, allowing the injection needle 1812 to be secured in either an extended or retracted position. Locking the injection needle 1812 prevents accidental movement of the needle during retinal procedures (e.g., subretinal injection), thereby reducing the risk of unwanted tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 1840 for adjustment, a user can press the toggle 1840 repeatedly, allowing the user to freely slide the toggle 1840 and thus freely extend or retract the injection needle 1812. In this example, the toggle 1840 may be movable only when pressed (e.g., activated) by the user. Correspondingly, releasing the toggle 1840 can cause the toggle 1840 to rise and lock in place, thereby locking the injection needle 1812 in position. This button locking mechanism can be facilitated in part by a spring rod provided with the handle 1802 and one or more rails including grooves or notches, along which the toggle 1840 can slide.

[0194] In some embodiments, the injection needle 1812 is coupled to an internal fluid shaft at least partially disposed within the cannula 1810, the internal fluid shaft serving as a fluid connection between the injection needle 1812 and the actuating element 1840 or a fluid conduit. In such embodiments, the internal fluid shaft may be slidably disposed within the cannula 1810 to facilitate the extension and retraction of the injection needle 1812 when the actuating element 1840 is actuated.

[0195] In some embodiments, a flexible fluid conduit 1820 for supplying injection fluid (e.g., non-therapeutic and / or therapeutic solutions) to the delivery device 1800 may be disposed through the proximal end 1806 of the handle 1802 and fluidly coupled within the handle 1802 to the injection needle 1812. In some embodiments, the fluid conduit 1820 may be coupled to the proximal end 1806 of the handle 1802, or to another fluid conduit within the handle 1802 (described elsewhere herein). Typically, the fluid conduit 1820 includes a supply line through which non-therapeutic and / or therapeutic solutions from a fluid source may be supplied to the delivery device 1800 for delivery to the eye. In some embodiments, the fluid source includes a fluid system that may be coupled to the fluid conduit 1820 via a connector 1822 (e.g., a Luer lock or other male-female connector). In some other embodiments, the handle 1802 may include an actuable lumen fluidly coupled to the injection cannula 1810 and accommodating the injection fluid. In such an embodiment, the subretinal delivery device 1800 may not be connected to any external fluid conduit.

[0196] In another embodiment, to simplify fluid preparation for subretinal injection and / or simplify the injection itself, fluid can be dispensed from a pre-filled cartridge ( Figure 18A (Not shown) A pre-filled cartridge provides a therapeutic agent to a delivery device 1800. This pre-filled cartridge may be coupled to a fluid drive system of the delivery device 1800 or to an external fluid system connected to the delivery device 1800 via a fluid conduit 1820. In some embodiments, the pre-filled cartridge comprises a single lumen containing a premixed therapeutic solution comprising components mixed in a suitable buffer solution at a desired ratio and / or concentration. Such embodiments facilitate a one-step subretinal injection procedure where a blister can be formed with the premixed therapeutic substance, rather than first forming a blister with a buffer solution and then injecting the therapeutic substance into the blister. Accordingly, the use of a pre-filled and premixed cartridge can facilitate more efficient and accurate dose concentration control. In yet other embodiments, the pre-filled cartridge may comprise two or more lumens containing unmixed therapeutic substances that can be automatically or semi-automatically mixed within, for example, a fluid system or delivery device prior to performing a subretinal injection. The cartridge for the therapeutic agent is described in further detail below.

[0197] In some embodiments, the injection needle 1812 may be further fluidly coupled to a second pre-filled cartridge or other fluid source configured to supply a colorant or labeling fluid to the injection needle 1812. In such embodiments, the second pre-filled cartridge or other fluid source may be configured to allow the colorant or labeling fluid to flow to the injection needle 1812 as the needle extends from the injection cannula 1810 and pierces the choroid. Accordingly, in such embodiments, the colorant or labeling fluid provides visualization of the position of the injection needle 1812 during injection and may be used to prevent the injection needle 1812 from extending through the subretinal space and into the sensory retina. The colorant or labeling fluid may be observed by a user via a microscope or other observation system having a viewing angle through the lens or sclera pointing towards the retina.

[0198] Turn now Figure 18B Except for the handle 1803, the delivery device 1801 is basically similar to the delivery device 1800. Figure 18B In this context, the handle 1803 can be described as a "minimum" handle because its size is reduced to an absolute minimum or near-absolute minimum dimension for extending and retracting the injection needle 1812 from the injection cannula 1810. For example, the handle 1803 has a length H that is the minimum length required to facilitate user actuation of the toggle 1840 to fully extend and retract the injection needle 1812. Figure 18B In this embodiment, the toggle 1840 includes a sliding button, and therefore, the length H is the minimum length required to support the toggle when it is translated to a first position that allows the injection needle 1812 to be fully extended from the cannula 1810 and to a second position that allows the injection needle 1812 to be fully retracted into the cannula 1810.

[0199] In some embodiments, the handle 1803 is also formed of a lightweight material. For example, the handle 1803 may be formed of a lightweight thermoplastic polymer material, which can typically be rigid. In some examples, the handle 1803 includes polyetheretherketone (PEEK), polyetherketone (PEK), and / or polytetrafluoroethylene (PTFE).

[0200] The reduced size and / or lightweight construction of the handle 1803 allows surgeons to focus their attention on the orientation and positioning of the injection cannula 1810 and / or the distal tip 1811 during access to and traverse of the suprachoroidal space, rather than on manipulating the handle 1803. For example, during routine subretinal injections using the suprachoroidal approach, surgeons may simultaneously utilize two sets of forceps: one set to keep the incision in the sclera open to allow the flexible injection cannula of the delivery device to enter, and another set to hold and insert the injection cannula. If the delivery device includes a large and / or heavy handle, the delivery device must also be supported during the procedure, complicating the procedure as the surgeon only has two hands. In such cases, another member of the surgical team may be needed to hold the delivery device as the surgeon guides the injection cannula into the patient's eye. However, using a “minimal” handle, such as… Figure 18B The handle 1803 in the middle circumvents this complexity. Because the handle 1803 is small in size and / or lightweight, neither the surgeon nor the surgical assistant needs to hold the handle during subretinal injection; instead, the handle 1803 can hang freely, as its size and weight allow it to hang freely without interfering with the procedure. Therefore, the surgeon can instead focus all their attention on manipulating the injection cannula 1810.

[0201] In another embodiment, the handle 1803 may include a Velcro strip 1890 or other fastening device that can be fastened to a corresponding feature on a headband or other article that is positioned or secured to, for example, a patient's head or other body part during the administration of a subretinal injection.

[0202] Figures 19A to 19C This demonstrates the compatibility with certain embodiments of this disclosure. Figures 18A to 18B Various views of exemplary injection cannulas used with delivery devices 1800 and 1801 or other delivery devices for subretinal injection as described herein. More specifically, Figure 19A and Figure 19B Three-dimensional diagrams of straight and curved injection cannulas 1910a and 1910b are shown respectively. Figure 19C A schematic cross-sectional top view of the injection cannula 1910c is shown to illustrate various exemplary cross-sectional profiles of injection cannulas used in conjunction with the delivery device 1800.

[0203] like Figure 19AAs shown, in some embodiments, the delivery device 1800 for performing subretinal choroidal injection includes a straight or substantially straight injection cannula 1910a. To facilitate easy traversal / sliding across the suprachoroidal space during such procedures, the injection cannula 1910a may be formed of a highly flexible material, which allows the injection cannula 1910a to conform to the curvature of the suprachoroidal space when positioned within it, thereby reducing strain on the choroid caused by the injection cannula 1910a. Accordingly, the flexibility of the axis can reduce or eliminate any damage to the retina and / or choroid during positioning the injection cannula 1910a for subretinal fluid delivery.

[0204] In some embodiments, the injection cannula 1910a is formed of any suitable flexible surgical-grade metallic material. Examples of flexible metallic materials include nitinol and other metal alloys. In some embodiments, the injection cannula 1910a is formed of any suitable flexible thermoplastic polymer material. Examples of suitable thermoplastic polymer materials include polyimide, thermoplastic polyurethane (TPU), polyether block amide (PEBA), etc.

[0205] In some embodiments, the injection cannula 1910a includes a lateral width W along its length L, which is greater than its vertical height H along the length L. Accordingly, in such embodiments, the injection cannula 1910a can be described as substantially “wide” and / or “flat”. These dimensions of the injection cannula 1910a can be advantageous when entering and traversing the suprachoroidal space, as they distribute strain along the wider surface (width W) of the injection cannula 1910a, thereby reducing the expansion of the suprachoroidal space as the injection cannula 1910a passes through it, and thus contributing to reduced choroidal and retinal damage. Furthermore, by reducing the lateral flexibility / bendability of the injection cannula 1910a in the direction parallel to its width W, the wide and / or flattened shape of the injection cannula 1910a allows the user better directional control over the injection cannula 1910a.

[0206] Turn now Figure 19BIn some embodiments, the delivery device 1800 for performing suprachoroidal subretinal injections includes a curved injection cannula 1910b. While in some examples, the injection cannula 1910b may be substantially similar to the injection cannula 1910a in terms of material and / or size (e.g., it is flexible and substantially wide and / or flat), the injection cannula 1910b includes a predefined curvature C along its length L, compared to the straight configuration of the injection cannula 1910a. In some embodiments, the curvature C of the injection cannula 1910b matches or substantially matches the curvature of the eye (eye 1900 is shown for reference) in the suprachoroidal space 1934 to reduce strain along the suprachoroidal space as the injection cannula 1910b passes through it, thereby reducing any damage to the choroid and / or retina. In some embodiments, to facilitate the curvature C of the injection cannula 1910b, the injection cannula 1910b may be formed of a more rigid material compared to those materials described above with reference to the injection cannula 1910a. For example, in some embodiments, the injection cannula 1910b may comprise aluminum, stainless steel, nitinol, and other metal alloys. In some embodiments, the injection cannula 1910b comprises polyimide, polyurethane (PUR), combinations thereof, etc.

[0207] Figure 19C A schematic cross-sectional top view (along the main longitudinal axis) of injection cannulas 1910c-1910e is shown to illustrate various exemplary cross-sectional profiles of injection cannulas used with delivery device 1800. As shown, on the left, the cross-sectional profile of cannulas 1910c has an elliptical shape; in the center, the cross-sectional profile of injection cannulas 1910d has a pill or rounded rectangular shape; on the right, the cross-sectional profile of injection cannulas 1910e has a crescent or "U" shape. In all examples, the cross-sectional profiles of injection cannulas 1910c-1910e further depict a channel 1911 passing through the injection cannulas, through which an injection needle (e.g., injection needle 1912) extends. Note that... Figure 19C The cross-sectional profiles shown are merely exemplary, and other cross-sectional profiles of the injection cannula, including rectangular profiles, are also envisioned.

[0208] Figures 20A to 20E This demonstrates the compatibility with certain embodiments of this disclosure. Figures 18A to 18B Various views of another exemplary injection cannula 2010 used in conjunction with delivery devices 1800 and 1801 or other delivery devices for subretinal injection as described herein. Figure 20A , Figure 20B and Figure 20C The images show a top cross-sectional view, a side cross-sectional view, and another side cross-sectional view of the injection cannula 2010. Figure 20D and Figure 20ECross-sectional views of the eye are shown at different steps of subretinal injection using the injection cannula 2010. Aspects of the injection cannula 2010 can be combined with other delivery devices and / or components described herein without limitation.

[0209] Turn now Figures 20A to 20C The tubular injection cannula 2010 includes a distal end 2014 and a proximal end 2016. The proximal end 2016 can be coupled to the handle of any suitable delivery device, such as the handle 1802 of the delivery device 1800 described above. The injection cannula 2010 further includes a first channel 2011a and a second channel 2011b formed therein, wherein each of channels 2011a and 2011b extends from or substantially near the distal end 2014 to or substantially near the proximal end 2016. As shown, channels 2011a and 2011b can be separated by one or more walls 2060 of the injection cannula 2010, or by any other suitable means, to form two distinct channels in the injection cannula 2010.

[0210] The injection needle 2012 is slidably coupled within the first channel 2011a and may terminate proximally within the injection cannula 2010 or terminate proximally within the handle of the injection cannula 2010. Typically, the injection needle 2012 is fluidly coupled directly or indirectly via a fluid conduit and / or other connector to a fluid source for supplying injection fluid (e.g., non-therapeutic and / or therapeutic solutions) to the injection needle 2012 for subretinal injection.

[0211] Simultaneously, the second channel 2011b can be configured to receive or cover the wire 2070. During subretinal injection via the suprachoroidal route, the wire 2070 can serve as a guidewire and / or reinforcing wire. For example, in some examples, the wire 2070 is configured as a guidewire to guide the injection cannula 2010 through the suprachoroidal space to the desired injection site. In such embodiments, the channel 2011b may have an open distal end 2064 to receive the wire 2070 (e.g., as the injection cannula 2010 is pushed through the suprachoroidal space). Figure 20C (As shown in the diagram). Further, channel 2011b may be connected to port 2062, which is configured to pass through the outer wall of injection cannula 2010, near the proximal end 2016 of injection cannula 2010, and the wire 2070 can be removed from channel 2011b through this port after injection cannula 2010 has been positioned in its final position for subretinal injection. In some embodiments, the proximal end 2066 of channel 2011b may open into an inner cavity coupled to a handle of injection cannula 2010, and the wire 2070 can be removed through the handle after injection cannula 2010 has been positioned in its final position for subretinal injection. See below for reference. Figure 20D and FIG. 20E The use of wire 2070 as a guide wire is described in further detail.

[0212] In some embodiments, the filament 2070 is configured as a reinforcing filament to increase the stiffness of the injection cannula 2010. For example, the filament 2070 may be made of a material with a stiffness greater than that of the injection cannula 2010 and may be inserted into the injection cannula 2010 to reduce the flexibility of the injection cannula during insertion and movement through the suprachoroidal lumen. In such embodiments, the channel 2011b may have a closed distal end 2064 to retain the filament 2070 within the channel 2011b as the injection cannula 2010 moves through the suprachoroidal lumen (e.g., ...). FIG. 20D (As shown in the diagram). Further, in such an embodiment, channel 2011b may also be connected to port 2062 located near the proximal end 2016 of injection cannula 2010. Therefore, before inserting injection cannula 2010 into the patient's eye and translating it through the suprachoroidal space, wire 2070 can be inserted into channel 2011b via port 2062 to provide increased rigidity. And, as described above, after injection cannula 2010 has been positioned for subretinal injection, wire 2070 can be removed from channel 2011b via port 2062, or removed together with injection cannula 2010 after injection. In other embodiments, the proximal end 2066 of channel 2011b may open into an inner cavity coupled to a handle of injection cannula 2010, and wire 2070 may be inserted into and / or removed from channel 2011b through the handle.

[0213] Typically, filament 2070 may comprise any suitable material for performing the guiding and / or reinforcing functions as described herein. For example, in some embodiments, filament 2070 comprises metallic materials such as stainless steel, aluminum, nitinol, or other metal alloys. In some other embodiments, filament 2070 comprises thermoplastic polymers such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0214] Now for reference FIG. 20D and FIG. 20E An exemplary method for using wire 2070 as a guidewire for subretinal injection is described. FIG. 2In step D, the wire 2070 is inserted into the patient's eye 2030 through the sclera 2032 and guided through the suprachoroidal space (SCS) 2034 to the target injection site 2036. Once the distal end of the wire 2070 in the suprachoroidal space 2034 is positioned adjacent to the target injection site 2036 in the subretinal space 2034, the injection cannula 2010 is inserted onto the wire 2070, such that the wire 2070 is received in the channel 2011b, and the injection cannula 2010 is slid along the wire 2070 until the distal end 2014 is positioned adjacent to the target injection site. At this point, the wire 2070 can be removed from the channel 2011b, for example, through the port 2062 or through the delivery device handle connected to the injection cannula 2010, or the wire 2070 can remain in the channel 2011b during injection via the injection needle 2012.

[0215] FIGS. 21A-21C Various views of an exemplary distal tip 2111 of an injection cannula according to certain embodiments of this disclosure are shown. More specifically, FIG. 21A and FIG. 21B A three-dimensional view of the distal end 2111 is shown, while FIG. 21C A schematic side section view of the distal end 2111 is shown. The distal end 2111 is... FIGS. 18A-18B The delivery devices 1800 and 1801, or other delivery devices and / or exemplary distal tips of injection cannulas as described herein for subretinal injection. Aspects of the distal tip 2111 can be combined with other delivery devices and / or components described herein without limitation.

[0216] like FIGS. 21A-21C As shown, the distal end 2111 includes a distal scraper portion 2160 and a proximal body portion 2162. In some embodiments, the distal end 2111 further includes a transition portion 2164 disposed between and connecting the scraper portion 2160 and the body portion 2162. The body portion 2162 is proximally connected to the injection cannula 2110 of the delivery device.

[0217] In some embodiments, the scraper portion 2160 has a vertical dimension S (e.g., FIG. 21CAs shown in the diagram, the vertical dimension S is smaller than the vertical dimension B of the main body portion 2162. In some embodiments, the vertical dimensions S and / or B are uniform or substantially uniform along the longitudinal length of the scraper portion 2160 and / or the main body portion 2162 (e.g., the length parallel to the main longitudinal axis A of the injection cannula). The reduced vertical dimension S of the scraper portion 2160 facilitates the stratification (i.e., separation) of the choroid and sclera as the distal tip 2111 moves through the suprachoroidal space to the target subretinal injection site. Simultaneously, the increased vertical dimension B of the main body portion 2162 facilitates the enclosure of the extendable injection needle 2112 within the main body portion 2162, which can be configured to extend from and retract into a port 2166 formed in the main body portion 2162.

[0218] In some embodiments, the transition portion 2164 has a varying vertical dimension T that increases proximally from the scraper portion 2160 to the body portion 2162. In other words, the vertical dimension T of the transition portion 2164 tapers from the body portion 2162 to the scraper portion 2162. In some embodiments, the vertical dimension T of the transition portion 2164 varies linearly along its longitudinal length. In some embodiments, the vertical dimension T of the transition portion 2164 varies non-linearly along its longitudinal length, and therefore, the transition portion 2164 may have curvature along its longitudinal length. The varying vertical dimension T of the transition portion 2164 creates a more gradual increase in vertical thickness between the scraper portion 2160 and the body portion 2162, thereby providing a more gradual increase in stress on the choroid and sclera as the distal end 2111 moves through the suprachoroidal space, and reducing damage to the tissue due to such movement.

[0219] Typically, while the distal end 2111 may include multiple varying vertical dimensions (e.g., S, T, and B), in some embodiments, the distal end 2111 may be as follows: FIG. 21A and FIG. 21B As shown, the distal end 2111 includes a uniform horizontal lateral dimension H (e.g., perpendicular to the main longitudinal axis A of the distal end 2111 and / or the cannula 2010) along its longitudinal length. However, in some other embodiments, the distal end 2111 may include two or more different horizontal lateral dimensions H along its longitudinal length.

[0220] Now return to FIG. 21CThe first side 2170 of the distal end 2111 may be substantially planar and coplanar with the injection cannula 1810, while the second side 2172 of the distal end 2111, opposite to the first side 2170, may have a stepped, inclined, tapered, or other varied side profile (e.g., along the longitudinal length of the distal end 2111) due to the different vertical dimensions of the scraper portion 2160, the transition portion 2164, and the body portion 2162. In yet another embodiment, as described below... FIG. 22A and FIG. 22B As described, the first side 2170 may also have a stepped, inclined, tapered, or other varied profile, which may be the same as or nearly the same as the second side 2172. When the distal end 2111 is moved through the suprachoroidal space, the distal end 2111 is oriented such that the first side 2170 faces the sclera (away from the choroid), while the second side 2172 faces the choroid.

[0221] like FIG. 21C As further shown, the internal lumen 2174 of the distal end 2111 may have an inclined surface 2180, the distance between this inclined surface and the first side 2170 increasing distally. This inclined surface 2180 can act as a "ramp" to facilitate the extension of the injection needle 2112 from the distal end 2111 in a direction not parallel to the main longitudinal axis A of the injection cannula 2110. This is necessary for suprachoroidal subretinal injection, as the injection needle must pierce the choroid along the suprachoroidal space (therefore, the injection needle 2112 must extend in a direction tangential to the main longitudinal axis A of the injection cannula 2110). Accordingly, as the injection needle 2112, disposed within the injection cannula 2110, extends through the distal end 2111, the inclined surface 2180 causes the injection needle 2112 to bend upwards away from the first side 2170 and slide along the inclined surface 2180 until the injection needle 2112 passes through the port 2166. To facilitate the upward bending of the needle 2112, the needle may include a flexible material, such as nitinol, polyimide, or other suitable flexible surgical-grade material.

[0222] FIG. 22A and FIG. 22B Various views of an exemplary distal tip 2211 of an injection cannula according to certain embodiments of this disclosure are shown. More specifically, FIG. 22A A three-dimensional view of the distal end 2211 is shown, while FIG. 22B A schematic side section view of the distal end 2211 is shown. The distal end 2211 is used for... FIGS. 18A-18B The delivery devices 1800 and 1801, or other delivery devices and / or injection cannulas as described herein for subretinal injection, may be used. Aspects of the distal end 2211 may be combined with other delivery devices and / or components described herein without limitation.

[0223] Similar to the distal end 2111, the distal end 2211 includes a distal scraper portion 2260, a proximal body portion 2262, and a transition portion 2264 disposed between and connecting the scraper portion 2260 and the body portion 2262. In some embodiments, the body portion 2262 is proximally connected to the injection cannula 2110 of the delivery device (in... FIG. 22A (shown in dashed lines). In some embodiments, the body portion 2262 is proximally coupled to a connector 2268, which can be configured to be inserted into and frictionally engaged with the distal end of the injection cannula 2110 to couple the distal end.

[0224] like FIG. 22A As shown, the scraper portion 2260 may have a substantially semi-circular disc shape with rounded edges 2282. The rounded edges 2282 and the semi-circular disc shape of the scraper portion 2260 facilitate easier separation of the choroid from the sclera while reducing damage to this tissue as the distal tip 2211 moves across the suprachoroidal space to the target injection site. In some embodiments, the scraper portion 2260 comprises a substantially flat (or planar) disc shape; in some other embodiments, the scraper portion 2260 comprises a curved disc shape substantially matching the curvature of the suprachoroidal space. Meanwhile, the body portion 2262 may have a cylindrical or substantially cylindrical shape, and the transition portion 2264 may have a triangular or ramp-like shape between the scraper portion 2260 and the body portion 2262.

[0225] The semi-circular disc-shaped scraper portion 2260 has a vertical dimension S1, which is smaller than the vertical dimension B1 of the cylindrical body portion 2262. In some embodiments, the vertical dimensions S1 and / or B1 are uniform or substantially uniform along the longitudinal length of the scraper portion 2260 and / or the body portion 2262 (e.g., the length parallel to the main longitudinal axis A of the injection cannula). The reduced vertical dimension S1 of the scraper portion 2260, in conjunction with the rounded edge 2282 and its disc-shaped shape, facilitates easier delamination of the choroid and sclera. Simultaneously, the increased vertical dimension B1 of the body portion 2262 facilitates the reception of an extendable injection needle 2212 within the body portion 2262, which can be configured to extend from and retract into a port 2266 formed in the body portion 2262.

[0226] In some embodiments, the transition portion 2264 has a vertical dimension T1 that varies proximally from the disc-shaped scraper portion 2260 to the cylindrical body portion 2262. In some embodiments, the vertical dimension T1 of the transition portion 2264 varies linearly along its longitudinal length. In some embodiments, the vertical dimension T1 of the transition portion 2264 varies non-linearly along its longitudinal length, and therefore, the transition portion 2264 may have curvature along its longitudinal length. The varying vertical dimension T1 of the transition portion 2264 creates a more gradual increase in vertical thickness between the scraper portion 2260 and the body portion 2262, thereby providing a more gradual increase in stress on the choroid and sclera as the distal end 2211 moves through the suprachoroidal space, and thus reducing damage to such tissue.

[0227] Turn now FIG. 22B The first side 2270 and the second side 2272 of the distal end 2211 both have stepped, inclined, tapered, or other varied side cross-sectional profiles (e.g., along the longitudinal length of the distal end 2211) due to the different shapes and thicknesses of the scraper portion 2260, the transition portion 2264, and the body portion 2262. In some embodiments, the side cross-sectional profiles of the first side 2270 and the second side 2272 are identical. In some other embodiments, the side cross-sectional profiles of the first side 2270 and the second side 2272 are different. For example, as... FIG. 22B As shown in the embodiments, the transition portion 2264 may have a steeper slope on the first side 2270 between the scraper portion 2160 and the body portion 2262, and a more gradual slope on the second side 2272 between the scraper portion 2160 and the body portion 2262. This difference in the contours of the first side 2270 and the second side 2272 can be used to account for the different fragility of the choroid and the sclera. For example, when the distal end 2211 is inserted and moved through the suprachoroidal cavity, the distal end 2211 is oriented such that the first side 2270 faces the sclera (away from the choroid), while the second side 2272 faces the choroid. Because the choroid is more fragile than the sclera, and the sclera is stronger than the choroid, the first side 2270 may have a steeper transition between the scraper portion 2260 and the body portion 2262, while the second side 2272 may have a more gradual transition between the scraper portion 2260 and the body portion 2262.

[0228] like FIG. 22BAs further shown, similar to the distal end 2111 described above, the internal lumen 2274 of the distal end 2211 may also have a sloping surface 2280, the distance between this sloping surface and the first side 2270 increasing distally. This sloping surface 2280 can act as a ramp to facilitate the extension of the injection needle 2212 from the distal end 2211 in a tangential direction relative to the main longitudinal axis A of the injection cannula 2210. Accordingly, when the extendable injection needle 2212 disposed within the injection cannula 2210 extends through the distal end 2211, the sloping surface 2280 causes the injection needle 2212 to bend upwards away from the first side 2270 and slide along the sloping surface 2280 until the injection needle 2212 passes through the port 2266. In some embodiments, to facilitate the upward bending of the needle 2212, the needle may comprise a flexible material, such as nitinol, polyimide, or other suitable flexible surgical-grade material.

[0229] FIG. 23A and FIG. 23B A side cross-sectional view of an exemplary internal ramp assembly 2300 of the distal end of an injection cannula for a subretinal delivery device according to certain embodiments of this disclosure is shown. The ramp assembly 2300 can be used in conjunction with any of the distal ends described herein (including distal ends 2111 and 2211 described above) to facilitate the extension of the injection needle from the distal end in a direction tangential to or non-parallel to the main longitudinal axis of the corresponding injection cannula.

[0230] like FIG. 23A and FIG. 23B As shown, the internal lumen 2374 of the distal end 2311 may include a sloped surface 2380 terminating distally at the port 2366 of the distal end 2311. In other embodiments described herein, this sloped surface 2380 may be used to directly guide a more conventional injection needle upward and "bend" out of the port 2366. However, in the current embodiment, the injection needle 2312 is proximally coupled to a slider 2382, which instead abuts against the sloped surface 2380 of the distal end 2311 to facilitate the extension and / or retraction of the injection needle 2312 through the port 2366. In some embodiments, the slider 2382 is made of a material that facilitates easy sliding of the injection needle 2312 with reduced frictional resistance, such as steel, titanium, PEEK (polyetheretherketone), polyoxymethylene (POM), polytetrafluoroethylene (PTFE), combinations thereof, etc.

[0231] The slider 2382 is proximally coupled to an inner fluid shaft 2386, which extends through the injection cannula of the delivery device to the handle of the delivery device. The inner fluid shaft 2386 fluidly connects the slider 2382 and the injection needle 2312 directly or indirectly to a fluid source or a fluid conduit connected to a fluid source. Accordingly, in some embodiments, the slider 2382 includes a fluid channel that facilitates the flow of injection fluid from the inner fluid shaft 2386 to the injection needle 2312 fluidly coupled to the slider 2382 for delivery to a target subretinal injection site. The inner fluid shaft 2386 may be further coupled to an actuator or other control mechanism disposed in the handle of the delivery device, allowing the user to manually actuate the inner fluid shaft 2386 through the injection cannula of the delivery device in a proximal or distal direction.

[0232] In some embodiments, the slider 2382 itself includes a distal inclined surface 2384 corresponding to (e.g., mating or engaging) the inclined surface 2380. In some embodiments, the inclined surface 2384 may be positioned at the same or substantially similar angle to the main longitudinal axis of the distal tip 2311 or the injection cannula coupled to the distal tip 2311. When a distally directed force (thrust) is applied to the slider 2382 from the proximal internal fluid axis 2386, the inclined surface 2384 may interact with the inclined surface 2380, causing the slider 2382 to translate upward (e.g., slide) along the inclined surface 2380, thereby allowing the injection needle 2312 to extend through the port 2366. FIG. 23B The ramp assembly 2300 is shown in the "extended" position. Similarly, when the internal fluid shaft 2386 applies a proximal (pulling) force to the slider 2382, the inclined surface 2384 can interact with the inclined surface 2380, causing the slider 2382 to translate downward (e.g., slide) along the inclined surface 2380, thereby causing the injection needle 2312 to retract through the port 2366. FIG. 23A The ramp assembly 2300 is shown in its "retracted" position. It should be noted that although the distal ramp surfaces 2384 and 2380 are depicted as planar "ramp-like" surfaces, other forms of such surfaces are also contemplated, including non-planar and / or curved surfaces. Furthermore, it is conceivable that ramp surface 2384 may have a different form than ramp surface 2380; for example, ramp surface 2384 may be rounded or curved, while ramp surface 2380 may be planar.

[0233] The described mechanism facilitates the extension and retraction of the injection needle 2312 through port 2366 without requiring the injection needle 2312 to bend. Accordingly, in addition to flexible materials such as polyimide, nitinol, etc., more rigid materials can also be used for the injection needle 2312. For example, in some embodiments, the injection needle 2312 may include metallic materials such as aluminum, stainless steel, nitinol, and other metal alloys. In other embodiments, the injection needle 2312 may include thermoplastic polymer materials such as polyimide, polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0234] Typically, the injection needle 2312 can be coupled to the slider 2382 at any desired angle or orientation. FIG. 23A and FIG. 23B In the example, the injection needle 2312 is connected to the slider 2382 at an angle that substantially matches the angles of the inclined surfaces 2380 and 2384.

[0235] FIG. 24A and FIG. 24B A schematic perspective view shows another exemplary distal end 2411 of an injection cannula 2410 for a delivery device according to certain embodiments of this disclosure. The distal end 2411 may be for... FIGS. 18A-18B The delivery devices 1800 and 1801, or other delivery devices and / or injection cannulas as described herein for subretinal injection, may be used. Therefore, aspects of the distal end 2411 can be combined with other delivery devices and / or components described herein without limitation.

[0236] Go to FIG. 24A The distal end 2411 includes a slotted port 2466 disposed through a sidewall 2468 of the distal end 2411. The slotted port 2466 may be oriented such that the length of the slotted port 2466 along the circumference of the distal end 2411 is greater than the width of the slotted port 2466 in the longitudinal direction (e.g., parallel to the main longitudinal axis A of the injection cannula 2410).

[0237] The injection needle 2412 is disposed within the distal end 2411 and the injection cannula 2410 and extends through the distal end and the injection cannula. For example... FIG. 24BAs shown, the injection needle 2412 includes a first extension 2480 that extends proximally through the entire length of the injection cannula 2410 and is coupled to an actuator or other suitable control mechanism disposed on a handle of a delivery device coupled to the injection cannula 2410. The injection needle 2412 further includes a second ferrule portion 2482 disposed at the distal end of the injection needle 2412. The ferrule portion 2482 includes a portion of the injection needle 2412 that is pre-shaped to bend or coil along a plane perpendicular to the main longitudinal axis of the extension 2480, such that the ferrule portion 2482 resembles a ferrule or helical shape. The ferrule portion 2482 is configured to extend from and retract into a slotted port 2466 when an actuator or other control mechanism, such as on the handle of the delivery device, rotates the extension 2480. For example, in some embodiments, the control mechanism may include a rotary knob or dial on the delivery device handle, and the user rotating the knob or dial may cause the extension 2482 to rotate, thereby causing the plug drill portion 2482 to rotate about the axis of the extension 2482 and extend out from the slotted port 2466.

[0238] Similar to FIG. 24A and FIG. 24B The described mechanism facilitates the efficient extension and retraction of the injection needle 2412 through the slotted port 2466 at a tangential angle relative to the injection cannula 2410, without requiring active bending of the injection needle 2412. Accordingly, in addition to flexible materials such as polyimide, nitinol, etc., more rigid materials can also be used for the injection needle 2412. For example, in some embodiments, the injection needle 2412 may comprise metallic materials such as aluminum, stainless steel, and other metal alloys. In other embodiments, the injection needle 2312 may comprise thermoplastic polymer materials such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0239] FIG. 25 A schematic perspective view shows an exemplary distal tip 2511 of an injection cannula 2510 for a delivery device according to certain embodiments of this disclosure. The distal tip 2511 is for... FIGS. 18A-18B The delivery devices 1800 and 1801, or other delivery devices and / or injection cannulas as described herein for subretinal injection, may be used. Therefore, aspects of the distal end 2511 can be combined with other delivery devices and / or components described herein without limitation.

[0240] As shown in the figure, the distal end 2511 includes a port 2566 in its sidewall 2568 for allowing an extendable injection needle 2512 to enter and exit. In some embodiments, the distal end 2511 includes an inclined surface or ramp within its internal lumen, which terminates distally at the port 2566 and facilitates the extension of the injection needle 2512 from the port 2566 at a tangential angle relative to the main longitudinal axis A of the distal end 2511 and / or the injection cannula 2510.

[0241] In addition to the port 2566 passing through the sidewall 2568, the distal end 2511 further includes a fluid port 2570 disposed through the distal surface 2572 of the distal end 2511. The fluid port 2570 may be fluidly coupled to a fluid line or fluid flow path extending through the distal end 2511, the injection cannula 2510, and / or coupled to the handle of the injection cannula 2510. The fluid line or flow path may include, for example, flexible fluid conduits, such as those described elsewhere herein for supplying injection fluid to an injection needle (e.g., injection needle 2512). Typically, the fluid line or flow path coupled to the fluid port 2570 may be further fluidly coupled to a fluid source for providing a water-separating fluid, such as a balanced salt solution (BSS) or other suitable fluid. During use, as the distal end 2511 moves through the suprachoroidal cavity, water-separating fluid can flow through a fluid line or flow path and out of the fluid port 2570 to delineate or separate the choroid from the sclera, and to make it easier for the user to position the distal end 2511 at the target injection site. Accordingly, in some embodiments, the fluid port 2570 is positioned through the distal surface 2572 of the distal end 2511, such that the water-separating fluid flows out of the distal surface 2572 in a direction 2580 parallel to or substantially parallel to the main longitudinal axis A of the distal end 2511 and / or the injection cannula 2510.

[0242] Now for reference FIG. 26A and FIG. 26B According to certain embodiments of this disclosure, another exemplary subretinal delivery device 2600 is shown in various perspective views. Delivery device 2600 is substantially similar to delivery device 1800 and can be used as, for example... FIG. 4 The delivery device 414 of the surgical system 400. Aspects of the delivery device 2600 can be combined with other delivery devices and / or components described herein without limitation. Certain aspects of the delivery device 2600 are related to the above references. FIG. 3 The described subretinal injection (and other related procedures) performed via the suprachoroidal route is particularly beneficial.

[0243] As shown in the figure, the delivery device 2600 includes a handle 2602 and a tubular injection cannula 2610 having a proximal end 2616 that is coupled to and extends distally from the distal end of the handle 2602. The distal end 2614 of the injection cannula 2610 includes a distal tip 2611 that may taper or be angled relative to the main longitudinal axis of the injection cannula 2610 to facilitate separation of the choroid from the sclera as the injection cannula 2610 moves through the suprachoroidal space. In some embodiments, the distal tip 2611 may have an oval, broadened, or flat cross-section to facilitate easier translation through the suprachoroidal space. Exemplary distal tips are discussed in more detail elsewhere herein. The injection cannula 2610 and / or the distal tip 2611 are typically formed of any suitable flexible surgical-grade material, such as a flexible metallic material or a thermoplastic polymer material. Examples of flexible metallic materials include nitinol and other metal alloys. Examples of suitable thermoplastic polymer materials include polyimide. In some embodiments, the distal end 2611 is formed of a rigid material, and the remainder of the injection cannula 2610 is formed of a flexible material.

[0244] like FIG. 26A and FIG. 26B As further shown, a curved or straight injection needle 2612 is disposed within the injection cannula 2610 for piercing the desired ocular tissue (here, the choroid and RPE) at an angle relative to the main longitudinal axis of the injection cannula 2610 to deliver fluid into the subretinal space. In an exemplary embodiment, the injection cannula 2610 is a 23, 25, or 27 gauge needle, while the injection needle 2612 is a finer gauge needle, such as a 38 gauge needle. However, in other embodiments, other sizes / gauges of injection cannulas and injection needles may be used. In some embodiments, as described elsewhere herein, the injection needle 2612 is formed of a flexible material, such as nitinol or polyimide. In some embodiments, the injection needle 2612 is formed of a rigid material, including metallic materials such as stainless steel, or thermoplastic polymers such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0245] In some embodiments, the injection needle 2612 is configured to slidably extend from and retract into the distal end 2614 of the injection cannula 2610, which helps prevent damage to the injection needle 2612 during insertion of the injection cannula 2610 into and / or movement within the patient's eye. This actuation of the injection needle 2612 can be controlled by any suitable control mechanism. FIG. 26AIn this embodiment, actuation of the injection needle 2612 is controlled by a first actuating element 2640 on the handle 2602. In some embodiments, the actuating element 2640 includes a sliding button or switch, wherein a user (e.g., a surgeon) slides the actuating element 2640 in a distal direction 2642 to extend the injection needle 2612 out of the injection cannula 2610, and slides the actuating element 2640 in a proximal direction 2644 to retract the injection needle 2612 back into the injection cannula 2610. In some embodiments, the injection needle 2612 is coupled to an internal fluid shaft at least partially disposed within the cannula 2610, the internal fluid shaft being used to fluidly connect the injection needle 2612 to a fluid conduit or to connect the injection needle 2612 to the actuating element 2640. In such embodiments, the internal fluid shaft may be slidably disposed within the cannula 2610 to facilitate the extension and retraction of the injection needle 2612 when the actuating element 2640 is actuated.

[0246] In some embodiments, the sliding toggle 2640 may also be lockable, allowing the injection needle 2612 to be secured in either an extended or retracted position. Locking the injection needle 2612 prevents accidental movement of the needle during retinal procedures (e.g., subretinal injection), thereby reducing the risk of unwanted tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 2640 for adjustment, a user can repeatedly press the toggle 2640, allowing the user to freely slide the toggle 2640 and thus freely extend or retract the injection needle 2612. In this example, the toggle 2640 may be movable only when pressed (e.g., activated) by the user. Correspondingly, releasing the toggle 2640 can cause the toggle 2640 to rise and lock in place, thereby locking the injection needle 2612 in position. This button locking mechanism can be facilitated in part by a spring rod provided with the handle 2602 and one or more tracks including grooves or notches, along which the toggle 2640 can slide.

[0247] like FIG. 26A As further shown, in some embodiments, a flexible fluid conduit 2620 for supplying injection fluid (e.g., non-therapeutic solutions and / or therapeutic solutions) to the delivery device 2600 may be disposed through the proximal end 2606 of the handle 2602 and fluidly coupled to the injection needle 2612 within the handle 2602. In some embodiments, the fluid conduit 2620 may be coupled to the proximal end 2606 of the handle 2602, or to another fluid conduit within the handle 2602 (described elsewhere herein). Typically, the fluid conduit 2620 includes a supply line from a fluid source ( FIG. 26AInjection fluid (non-therapeutic solution and / or therapeutic solution, not shown) can be provided through the supply line to delivery device 2600 for delivery to the eye. In some embodiments, the fluid source includes a fluid system that can be coupled to fluid conduit 2620 via connector 2622 (such as a Luer lock or other male-female connector). In some other embodiments, handle 2602 may include an actuable lumen fluidly coupled to injection cannula 2610 and accommodating injection fluid ( FIG. 26A (Not shown in the image). In such an embodiment, the subretinal delivery device 2600 may not be connected to any external fluid conduit.

[0248] In another embodiment, to simplify fluid preparation for subretinal injection and / or to simplify the injection itself, the therapeutic agent can be supplied from a pre-filled cartridge to the delivery device 2600, which can be directly coupled to the delivery device 2600 or coupled to a fluid system connected to the delivery device 2600 via fluid conduit 2620. The cartridge for the therapeutic agent is described in more detail elsewhere herein.

[0249] The delivery device 2600 further includes a reinforcing sleeve 2670. The reinforcing sleeve 2670 is slidably coupled to the injection cannula 2610, and... FIG. 26A and FIG. 26B In one embodiment, it substantially surrounds at least a portion of the injection cannula 2610. However, in some other embodiments, a reinforcing sleeve 2700 may be disposed within the injection cannula 2610 and function substantially similarly.

[0250] The reinforcing sleeve 2670 is adjustable relative to the injection cannula 2610, allowing the user to manually position the reinforcing sleeve 2670 (e.g., the distal end of the reinforcing sleeve 2670) at different points along the length L of the injection cannula 2610 outside the handle 2602 (e.g., ...). FIG. 26B(As shown in the diagram). Accordingly, the user can selectively adjust (e.g., increase or decrease) the stiffness level of a portion of the injection cannula 2610 by adjusting the position of the reinforcing sleeve 2670 relative to the distal end 2614 of the injection cannula 2610, thereby manipulating the amount of support provided to the injection cannula 2610 and stabilizing the injection cannula 2610 during its use. Thus, the reinforcing sleeve 2670 allows for selectively increasing the stiffness of the injection cannula 2610 to facilitate easier access to and access to the suprachoroidal space, while also allowing for selectively decreasing the stiffness of the injection cannula 2610 once it has entered the suprachoroidal space, to facilitate the injection cannula 2610 conforming to the curvature of the patient's eye, thereby reducing stress on the choroid and sclera. For example, before / during the insertion of the injection cannula 2610 into the suprachoroidal space, the reinforcing sleeve 2670 can be fully extended to increase the stiffness of the injection cannula 2610, thereby facilitating better control and / or maneuverability and improving overall safety and ease of use. Once inserted into the suprachoroidal space, the reinforcing sleeve 2670 can be retracted to reduce the stiffness of the injection cannula 2610. For example, as the injection cannula 2610 is pushed further into the suprachoroidal space, the reinforcing sleeve 2670 can be retracted to facilitate the flexibility of the injection cannula 2610 within the suprachoroidal space, thereby reducing stress and damage to the choroid, including the risk of choroidal hemorrhage.

[0251] The reinforcing sleeve 2670 is typically a cylindrical, hollow tube that substantially surrounds a portion of the injection cannula 2610 at or near its proximal end 2616. In some embodiments, the reinforcing sleeve 2670 has a uniform lateral dimension along its longitudinal or axial length, thus resembling a simple cylinder. In some embodiments, the reinforcing sleeve 2670 has a non-uniform lateral dimension along its longitudinal or axial length and may resemble a tapered cylinder. The reinforcing sleeve 2670 is typically formed of a suitable surgical-grade material with suitable stiffness to provide increased stiffness or support to the injection cannula 2610. In some embodiments, the reinforcing sleeve 2670 is formed of a metallic material, such as stainless steel, aluminum, or titanium. In other embodiments, the reinforcing sleeve 2670 is formed of a composite material, such as a thermoplastic polymer composite or a ceramic composite. For example, the reinforcing sleeve 2670 may comprise polyetheretherketone (PEEK), polyetherketone (PEK), and / or polytetrafluoroethylene (PTFE). In some embodiments, the reinforcing sleeve 2670 comprises polycarbonate (PC).

[0252] The reinforcing sleeve 2670, together with the injection cannula 2610, is disposed through an opening 2672 in the distal end 2604 of the handle 2602. The proximal end of the reinforcing sleeve 2670 is disposed within the lumen or cavity of the handle 2602. The size of the reinforcing sleeve 2670 is determined to have a longitudinal (i.e., axial) length sufficient to provide the desired rigidity and stability to the injection cannula 2610, while a portion of the reinforcing sleeve remains within the handle 2602 when the reinforcing sleeve 2670 is in the fully extended or extended position.

[0253] As described above, the reinforcing sleeve 2670 is configured to slidably extend from and retract into the opening 2672 of the handle 2602. This actuation of the reinforcing sleeve 2670 can be controlled by any suitable control mechanism. FIG. 26A In this embodiment, actuation of the reinforcing sleeve 2670 is shown as controlled by a second toggle 2674 on the handle 2602. In some embodiments, the toggle 2674 includes a sliding button or switch, similar to the toggle 2640, wherein sliding the toggle 2674 in the distal direction 2642 causes the reinforcing sleeve 2670 to extend from the opening 2672, and sliding the toggle 2674 in the proximal direction 2644 causes the reinforcing sleeve 2670 to retract into the opening 2672. Alternatively, where the toggle 2674 includes a button, the extension and / or retraction of the reinforcing sleeve 2670 can be controlled via pressing or releasing the toggle 2674.

[0254] In some embodiments, the actuator 2674 may also be lockable, such that the reinforcing sleeve 2670 can be fixed in place along length L after user adjustment. In some examples, the actuator 2674 may be lockable in one or more preset positions corresponding to progressively preset positions of the reinforcing sleeve 2670 along length L of the injection cannula 2610, wherein such preset positions of the reinforcing sleeve 2670 further correspond to a predetermined stiffness level of the injection cannula 2610. Locking the reinforcing sleeve 2670 prevents accidental movement of the reinforcing sleeve 2670 during surgical procedures (e.g., subretinal injection), thereby reducing the risk of accidental over- or under-reinforcing of the injection cannula 2610 when positioning it within the patient's eye. In some examples where the actuator 2674 is a sliding button, to unlock / release the actuator 2674 for adjustment, the user can press the actuator 2674 repeatedly, allowing the user to freely slide the actuator 2674 and thus freely extend or retract the reinforcing sleeve 2670. In this example, the toggle 2674 may be movable only when pressed (e.g., activated) by the user. Correspondingly, releasing the toggle 2674 causes it to rise and lock in place, thereby locking the reinforcing sleeve 2670 in place. This locking mechanism may be facilitated in part by utilizing a spring rod disposed together with the handle 2602 and one or more tracks including grooves or notches along which the toggle 2674 may slide.

[0255] FIG. 27A and FIG. 27B Various perspective views of another exemplary subretinal delivery device 2700 according to certain embodiments of this disclosure are shown. Delivery device 2600 is substantially similar to delivery devices 1800 and 2600 and can be used as, for example... FIG. 4 The delivery device 414 of the surgical system 400. Aspects of the delivery device 2700 can be combined with other delivery devices and / or components described herein without limitation. Similar to the aforementioned delivery device 2600, certain aspects of the delivery device 2700 are as referenced above. FIG. 3 The described subretinal injection (and other related procedures) via the suprachoroidal route is particularly advantageous. More specifically, aspects of the delivery device 2700 are conducive to improving the ergonomics of the user during suprachoroidal subretinal injection because the delivery device 2700 can be held horizontally rather than vertically during the administration of such an injection.

[0256] like FIG. 27AAs shown, the delivery device 2700 includes a handle 2702 for user holding. In some embodiments, a flexible fluid conduit 2720 for supplying injection fluid to the delivery device 2700 may be disposed through a proximal end 2706 of the handle 2702 and fluidly coupled within the handle 2702 to a tubular injection cannula 2710. In some embodiments, the fluid conduit 2720 may be coupled to the proximal end 2706 of the handle 2702, or to another fluid conduit within the handle 2702 (described elsewhere herein). In some other embodiments, the handle 2702 may include an actuable lumen fluidly coupled to the injection cannula 2710 and receiving the injection fluid. FIG. 27A (Not shown in the image). In such an embodiment, the subretinal delivery device 2700 may not be coupled to any external fluid conduit. In another embodiment, to simplify fluid preparation for subretinal injection and / or to simplify the injection itself, therapeutic agents or other injection fluids may be supplied to the delivery device 2700 from a pre-filled cartridge, which may be coupled to a fluid drive system within the delivery device 2700 or to an external fluid system connected to the delivery device 2700 via fluid conduit 2720. The cartridge for therapeutic agents is described in more detail elsewhere herein.

[0257] The proximal end 2776 of the bend-axis adapter 2770 is coupled to and extends from the distal end 2704 of the handle 2702. The bend-axis adapter 2770 allows the user to hold the delivery device 2700 horizontally rather than vertically during subretinal injections or other procedures, thereby improving stability, control, and overall safety when using the delivery device 2700. Furthermore, the delivery device 2700, when held horizontally by the user, does not interfere with the optics of any visualization system being used (such as a microscope). Accordingly, the bend-axis adapter 2770 improves the ergonomics of using the delivery device 2700. In some embodiments, the bend-axis adapter 2770 includes a curved, coiled, or bent hollow tube.

[0258] The axis adapter 2770 can be defined by any curvature suitable for performing subretinal injection via the suprachoroidal route. For example, in some embodiments, the axis adapter 2770 has a radius of curvature R between 1 mm and about 20 mm, such as between about 5 mm and about 15 mm, such as about 10 mm. In some embodiments, due to the curvature of the axis adapter 2770, the distal end 2774 of the axis adapter 2770 has a main axis S set at an angle between 0 degrees and 90 degrees relative to the main longitudinal axis A of the handle 2702. For example, in some embodiments, the main axis S (and the main longitudinal axis of the cannula 2710) is set at an angle between 30 degrees and 60 degrees relative to the main axis A, such as at an angle of 45 degrees relative to the main axis A. In some embodiments, the main axis S (and the main longitudinal axis of the cannula 2710) is set at an angle between 45 degrees and 90 degrees relative to the main axis A, such as at an angle between about 60 degrees and 75 degrees relative to the main axis A. Typically, the curvature of the shaft adapter 2770 is such that any pipes and / or fluids within the shaft adapter 2770 are not negatively affected by the curvature (e.g., the curvature does not cause kinking or slippage of the shaft adapter), and such that the distance from the proximal end 2706 of the handle 2702 to the distal end 2774 of the shaft adapter 2770 is not too long for ergonomic use.

[0259] In some embodiments, the bending shaft adapter 2770 may be formed of a rigid material, such as a rigid metal or a polymer. Examples of rigid metals include stainless steel, aluminum, and titanium.

[0260] The proximal end 2716 of the extendable injection cannula 2710 is coupled to the distal end 2774 of the shaft adapter 2770. The extendable injection cannula 2710 is configured to slidably extend from and retract into the distal end 2774 of the shaft adapter 2770, which allows the injection cannula 2710 to extend through the suprachoroidal space to the target injection site after insertion into the patient's eye. This actuation of the injection cannula 2710 can be controlled by any suitable control mechanism. FIG. 27A In this embodiment, actuation of the injection cannula 2710 is controlled by a toggle 2740 on the handle 2702. In some embodiments, the toggle 2740 includes a sliding button or switch, wherein the user slides the toggle 2740 in the distal direction 2742 to extend the injection cannula 2710 from the shaft adapter 2770, and slides the toggle 2740 in the proximal direction 2744 to retract the injection cannula 2710 into the shaft adapter 2770.

[0261] The injection cannula 2710 further includes a distal tip 2711 disposed at its distal end 2714. In some embodiments, the distal tip 2711 may have a tapered or sloping (e.g., ramp-like) profile to facilitate movement through the suprachoroidal lumen. In some embodiments, the distal tip 2711 may have an oval, broadened, or flat cross-section to facilitate easier translation through the suprachoroidal lumen. Exemplary distal tips are discussed in more detail elsewhere herein. The injection cannula 2710 and / or the distal tip 2711 are generally formed of any suitable flexible surgical-grade material, such as a flexible metallic material or a thermoplastic polymeric material. Examples of flexible metallic materials include nitinol and other metal alloys. Examples of suitable thermoplastic polymeric materials include polyimide. In some embodiments, the distal tip 2711 is formed of a rigid material, and the remainder of the injection cannula 2710 is formed of a flexible material.

[0262] Turn now FIG. 27B A curved or straight injection needle 2712 is coupled to a distal end 2711. In some embodiments, the injection needle 2712 is configured to slidably extend from and retract from the distal end 2711, which helps prevent injury to the injection needle 2712 and / or the patient's eye during the movement of the injection cannula 2710 through the suprachoroidal space. This extension / retraction of the injection needle 2712 can be controlled by any suitable control mechanism, such as a toggle on the handle 2702 separate from the toggle 2740. In exemplary embodiments, the injection cannula 2710 is a 23, 25, or 27 gauge needle, while the injection needle 2712 is a finer gauge needle, such as a 38 gauge needle. However, in other embodiments, other sizes / gauge injection cannulas and injection needles may be used.

[0263] In some embodiments, as described elsewhere herein, the injection needle 2712 is formed of a flexible material, such as nitinol or polyimide. In some embodiments, the injection needle 2712 is formed of a rigid material, including metallic materials such as stainless steel, or thermoplastic polymers such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE).

[0264] FIGS. 28A-28D Various views of an exemplary guide cannula 2800 according to certain embodiments of this disclosure are shown. The guide cannula 2800 can be used with other delivery devices described herein (e.g., FIGS. 18A-18B The delivery devices 1800 and 1801 are used in conjunction with the guide cannula 2800. Therefore, aspects of the guide cannula 2800 can be combined with other delivery devices and / or components described herein without limitation.

[0265] Typically, the guiding cannula 2800 includes an expandable and flexible cannula configured to provide a predefined channel through which the injection cannula of the delivery device can be inserted to be guided and translated across the suprachoroidal space to the target injection site. For example, the guiding cannula can be first inserted into the patient's eye and advanced across the suprachoroidal space until its distal end is positioned adjacent to the target injection site. Thereafter, the guiding cannula can be expanded, and the injection cannula can be inserted into the expanded guiding cannula and advanced through it until the distal end of the injection cannula reaches the target injection site (e.g., until the distal end of the injection cannula passes the distal end of the guiding cannula). Therefore, the guiding cannula facilitates easier manipulation and positioning of the injection cannula during its entry and positioning within the suprachoroidal space. Furthermore, because the guiding cannula does not need to include an injection needle or any fluid, it can have a smaller lateral dimension compared to the injection cannula of the delivery device. Accordingly, guided cannulation can apply less strain to the choroid during its insertion, which can reduce the overall damage to the choroid during subretinal injection on the choroid.

[0266] Turn now FIG. 28A The figure depicts a side cross-sectional view of a guide cannula 2800. As shown, the guide cannula 2800 includes a hub 2870 and a tube 2880. The tube 2880 is coupled to and extends distally from a bottom (e.g., distal) surface 2872 of the hub 2870. The tube 2880 is configured to be inserted into and through the suprachoroidal lumen, and is further configured to facilitate insertion and advancement of an injection cannula therein. Accordingly, in some embodiments, the tube 2880 may be generally tubular, having a circular, elliptical, or pill-shaped cross-sectional top profile (e.g., as viewed along the longitudinal length of the tube 2880). However, other top cross-sectional morphologies are also contemplated for the tube 2880, as described below. Further, the tube 2880 includes a centrally located guide channel 2882 extending from an opening 2851 at its proximal end 2853 to an opening 2855 at its distal end 2857. The guide channel 2882 and openings 2851 and 2855 allow the injection cannula to pass through both ends of the tube 2880.

[0267] In some embodiments, the hub 2870 may be substantially cylindrical or annular, but other forms are also contemplated. The hub 2870 includes a central channel 2878 fluidly coupled to an opening 2851 of a guide channel 2882, and is further surrounded and partially defined by an inner wall 2897 of the hub 2870. In some embodiments, the hub 2870 may act as a stop or retention device to prevent the tube 2880 from entering too far into the suprachoroidal space during insertion. Accordingly, the bottom surface 2872 of the hub 2870 may be configured flush with the surface of the patient's eye, and the hub 2870 may have an outer diameter (or other lateral dimension) larger than the outer diameter of the tube 2880. Additionally, the hub 2870 may act as an adapter to facilitate easier insertion of the injection cannula into the tube 2880. Therefore, the top (e.g., proximal) surface 2874 and / or inner wall 2897 may have an inclined, sloping and / or conical shape to mechanically guide the injection cannula into the guide channel 2882 of the tube 2880.

[0268] In some embodiments, the hub 2870 and the tube 2880 are integrally formed such that they comprise the same material. For example, both the hub 2870 and the tube 2880 may be formed of flexible and expandable materials such as silicone, polyurethane (PUR), polyether block amide (PEBA), polyolefins, combinations thereof, etc. In some other embodiments, the hub 2870 and the tube 2880 may comprise different materials. For example, the hub 2870 may be formed of a rigid or non-expandable material, such as a metallic material like stainless steel, aluminum, titanium, or other metal alloys, or the hub 2870 may be formed of a thermoplastic polymer such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE); while the tube 2880 may be formed of a flexible / elastic and expandable material such as plastic, metal, polymer, nitinol, or combinations thereof.

[0269] like FIG. 28AAs further shown, in some embodiments, hub 2870 and / or tube 2880 include expansion channel 2890. Expansion channel 2890 may be disposed within wall 2876 of hub 2870 and / or wall 2886 of tube 2880. In some embodiments, expansion channel 2890 is externally connected to at least a portion of guide channel 2882 centrally formed within tube 2880. In some embodiments, expansion channel 2890 is externally connected to the entire or nearly the entire longitudinal length of guide channel 2882 centrally formed within tube 2880. In some embodiments, channel 2890 is fluidly coupled to closable port 2892 formed in hub 2870 and / or tube 2880. Closable port 2892 allows access to and from channel 2890 from outside the guide cannula 2800. Accordingly, channel 2890 may be filled with fluid to expand tube 2880 (hub 28170 in some embodiments), thereby increasing at least the lateral dimension (e.g., diameter) of tube 2880, and thus increasing the lateral dimension (e.g., diameter) of guide channel 2882 to facilitate the entry and passage of the injection cannula of the delivery device through tube 2880. In some embodiments, channel 2890 may be filled with a gas, such as air, oxygen, nitrogen (N2), or other gases. In some embodiments, channel 2890 may be filled with a liquid, such as perfluorocarbon liquid (PFCL), BSS, saline, or other liquids. In some embodiments, channel 2890 may be filled with a combination of liquid and gas.

[0270] However, in some embodiments, the tube 2880 can be expanded by other means, including mechanical means. For example, in some embodiments, the tube 2880 can expand by utilizing the inherent spring-like action of the braided yarn when it is twisted by the user. The braided yarn can be disposed in an expansion channel 2890 within the wall 2886 of the tube 2880, or the braided yarn can be disposed within a guide channel 2882 and circumferentially lined within the guide channel. However, other mechanical means for expanding the tube 2880 are further contemplated.

[0271] In some embodiments, the guide cannula 2800 may not include any separate expansion mechanism or device, other than being formed of a flexible material. For example, in such an embodiment, the tube 2880 may be potentially expanded by an injection cannula inserted through it, which may have an outer diameter larger than the lateral dimension (e.g., diameter) of the guide channel 2882. Thus, the tube 2880 may expand as the injection cannula is advanced through the tube 2880.

[0272] In some embodiments, the expandability of tube 2880 can be optimized based on its cross-sectional profile. For example, in some embodiments, tube 2880 may have a star-shaped cross-sectional profile or other suitable shape, such that the expansion of tube 2880 is caused by the "unfolding" of wall 2886 rather than the stretching of wall 2886, or by the "unfolding" of wall in addition to the stretching of wall. A top cross-sectional view of an exemplary star-shaped cross-sectional profile of tube 2880 is shown in [the image / image / etc.]. FIG. 28B The diagram is provided for reference. The expansion of wall 2886 can reduce the stress on tube 2880 during expansion and / or reduce the amount of fluid pressure or force required to expand tube 2880, thereby facilitating easier and more reliable expansion of tube 2880 during use.

[0273] FIG. 28C and FIG. 28D A schematic side-section view of an exemplary guide cannula 2800 during use is shown. FIG. 28C First, the guiding cannula 2800 is inserted into the suprachoroidal space 2806 of the patient's eye 2804 and advanced through the suprachoroidal space 2806 until the distal end 2857 of the cannula 2880 is positioned adjacent to the target injection site 2808. Afterwards, in FIG. 28D In this process, the guiding cannula 2800 can be dilated, for example, by allowing fluid to flow into the dilation channel 2890 (and sealing the closable port 2892). Then, the injection cannula 2810 of the delivery device 2802 can be inserted and advanced through the dilated guiding cannula 2800, and more specifically, through the tube 2880, until the distal end of the injection cannula 2810 passes the distal end 2857 adjacent to the target injection site 2808. At this point, the injection needle of the injection cannula 2810 can be extended to pierce the choroid to inject fluid into the subretinal space.

[0274] FIGS. 29A-29C Various views of an exemplary access cannula 2900 according to certain embodiments of this disclosure are shown. The access cannula 2900 is an exemplary access cannula that can be used to facilitate the passage of an injection cannula through the sclera of the eye into the suprachoroidal space, as referenced above. FIG. 3 Described. Accordingly, insertion into the cannula 2900 can be, for example, FIGS. 18A-18B Delivery devices 1800 and 1801, delivery device 2600 of FIG. 26, and other delivery devices for subretinal injection described herein may be used in combination. However, aspects of the insertion cannula 2900 may be combined with other delivery devices and / or components described herein without limitation.

[0275] Turn now FIG. 29AThe insertion cannula 2900 includes a tubular body 2902 having a central channel 2908 extending from a proximal end 2904 of the body 2902 to a distal end 2906 of the body 2902. After the insertion cannula 2900 is inserted through the sclera of the patient's eye, the central channel 2908 serves as the entry point or port for subsequent insertion of an injection cannula for the delivery device. Accordingly, the central channel 2908 may have a lateral dimension (e.g., diameter) along its longitudinal length that is substantially equal to or greater than the lateral dimension of the injection cannula to be inserted therethrough. In some embodiments, the central channel 2908 has a uniform dimension from the proximal end 2904 to the distal end 2906. In some embodiments, the central channel 2908 has a non-uniform lateral dimension from the proximal end 2904 to the distal end 2906; for example, the central channel 2908 may have a larger lateral dimension at or near the proximal end 2904 compared to the distal end 2906.

[0276] In some embodiments, the body 2902 may have a generally circular cross-sectional profile. In some other embodiments, such as FIG. 29A As shown, the body 2902 may have a “flat” cross-sectional profile, which may resemble an elliptical or oval shape, or a pill or rounded rectangle shape.

[0277] In some embodiments, the body 2902 includes a distal scraper portion 2960 and a proximal entry portion 2962, the distal scraper portion including a distal end 2906 and the proximal entry portion including a proximal end 2904. Typically, the scraper portion 2960 may have a ramp or wedge shape, such that the vertical dimension S1 of the scraper portion 2960 at the distal end 2906 gradually transitions proximally to the vertical dimension S2 of the scraper portion 2960. The ramp or wedge shape facilitates choroidal delamination (i.e., separation) as the distal end 2906 of the insertion cannula 2900 is advanced into the suprachoroidal space after passing through the sclera of the patient's eye. In some embodiments, the scraper portion 2960 includes an incision 2963 formed in the sidewall of the body 2902, which is fluidly connected to the central channel 2908 and improves delamination efficiency.

[0278] In some embodiments, the scraper portion 2960 is formed of a rigid material, including metallic materials such as aluminum, stainless steel, and other metal alloys, or thermoplastic polymeric materials such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE). In some other embodiments, the scraper portion 2960 is formed of a flexible material, including metallic materials such as nitinol, and thermoplastic polymeric materials such as polyimide. Using a flexible material for the scraper portion 2960 can reduce strain on the choroid, retina, and / or sclera during insertion of the cannula 2900, thereby reducing choroidal, retinal, and / or scleral damage caused by insertion of the cannula 2900 during use.

[0279] Simultaneously, the entry portion 2962 may be tubular and is typically configured to facilitate the insertion and advancement of the injection cannula into the entry cannula 2900. In some embodiments, the entry portion 2962 is formed of a rigid material, including metallic materials such as aluminum, stainless steel, and other metal alloys, or thermoplastic polymeric materials such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE). In some other embodiments, the entry portion 2962 is formed of a flexible material, including metallic materials such as nitinol, and thermoplastic polymeric materials such as polyimide. In some embodiments, the entry portion 2962 and the scraper portion 2960 may be formed of the same material, and therefore, the body 2902 may comprise a single integral component. However, in some other embodiments, the entry portion 2962 and the scraper portion 2960 may be formed of different materials.

[0280] In some embodiments, the entry portion 2962 may optionally include one or more retaining arms 2970 coupled to the entry portion (in... FIG. 29ATwo fixation arms 2970 are shown, extending laterally from opposite sides of the entry portion 2962. These one or more fixation arms 2970 can be configured to act as "stops" to hold the entry cannula 2900 in place after it has been inserted through the sclera and advanced to the desired depth in the suprachoroidal space. Accordingly, once the entry cannula 2900 has been advanced to the desired depth, the fixation arms 2970 can be configured to contact the outer surface of the sclera outside the incision through which the scraper portion 2960 and a portion of the entry portion 2962 are inserted, thereby preventing further advancement of the entry cannula 2900 into the patient's eye. Therefore, these one or more fixation arms 2970 can prevent any unintended movement of the entry cannula 2900 after its final positioning, thereby reducing the risk of damage to the choroid, retina, and / or sclera, and facilitating improved control of the injection cannula's positioning during subretinal injection. In some embodiments, these one or more fixation arms 2970 can be fixedly coupled to the entry portion 2962. In some other embodiments, the one or more retaining arms 2970 may be extendably coupled to the entry portion 2962, thereby allowing the one or more retaining arms 2970 to extend laterally outward from the entry portion 2962 or perpendicular to the main longitudinal axis of the insertion cannula 2900 during use. Typically, the retaining arms 2970 can have any suitable size and shape. FIG. 29A In the example, the fixing arm 2970 is depicted as a curved or bent wire resembling a "bull's horn," which can extend laterally from the entry portion 2962.

[0281] FIG. 29B and FIG. 29C A 3D view of the 2900 cannula during use is shown. FIG. 29B In this procedure, an access cannula 2900 is first inserted through an incision 2994 in the sclera 2992 of the patient's eye 2990. In embodiments including a fixation arm 2970, the access cannula 2900 is inserted through the incision until the one or more fixation arms 2970 contact the sclera 2992. In some embodiments, a trocar may be used in conjunction with the access cannula 2900 to cut the sclera 2992. For example, the trocar may be positioned to pass through and extend from the distal end of the central channel 2908 of the access cannula 2900. The portion of the trocar extending from the central channel 2908 is then inserted into the eye 2990, forming an incision, until the bottom surface of the one or more fixation arms 2970 contacts the sclera 2992. The trocar can then be removed from the eye 2990, leaving the access cannula 2900 in place.

[0282] After that, FIG. 29CIn this method, the injection cannula 2910 of the delivery device can be inserted and advanced through the access cannula 2900 until the distal end of the injection cannula 2910 is positioned adjacent to the target subretinal injection site for injection. The access cannula 2900 allows the user to observe the advancement of the injection cannula 2910 through the suprachoroidal space via a microscope, without requiring the user to focus on the injection cannula 2910 sliding through the scleral incision. This ultimately facilitates better control and more efficient placement of the injection cannula 2910, while also reducing the risk of damage to ocular tissues.

[0283] FIG. 30A and FIG. 30B A perspective view of another exemplary access cannula 3000 according to certain embodiments of this disclosure is shown. Similar to access cannula 2900, access cannula 3000 is an exemplary access cannula that can be used to facilitate the entry of an injection cannula for delivery of a device through the sclera of the eye into the suprachoroidal space, as referenced above. FIG. 3 Described. Accordingly, the insertion of the cannula 3000 can be, for example, with FIGS. 18A-18B Delivery devices 1800 and 1801, delivery device 2600 of FIG. 26, and other delivery devices for subretinal injection described herein may be used in combination. However, aspects of the insertion cannula 3000 may be combined with other delivery devices and / or components described herein without limitation.

[0284] As shown in the figure, the insertion cannula 3000 includes a tubular body 3002 having a central channel 3008 extending from a proximal end 3004 of the body 3002 to a distal end 3006 of the body 3002. After the insertion cannula 3000 is inserted through the sclera of the patient's eye, the central channel 3008 serves as the entry point or port for the subsequent insertion of an injection cannula for the delivery device. Accordingly, the central channel 3008 may have a lateral dimension along its longitudinal length that is substantially equal to or greater than the lateral dimension of the injection cannula to be inserted through it.

[0285] In some embodiments, the body 3002 includes a distal tubular portion 3060 and a proximal funnel portion 3062, the distal tubular portion including a distal end 3006 and the proximal funnel portion including a proximal end 3004. The distal tubular portion 3060 is generally tubular and may have a top cross-section resembling a circular or oval shape. FIG. 30A and FIG. 30BAs shown, the end face 3068 of the tube portion 3060 may be positioned at a non-right angle relative to the main longitudinal axis of the tube portion 3060, thereby forming a ramp or wedge shape at the distal end 3006. This ramp or wedge shape facilitates the stratification (i.e., separation) of the choroid as the distal end 3006 of the cannula 3000 is advanced into the suprachoroidal space after passing through the sclera of the patient's eye. In some embodiments, the tube portion 3060 is formed of a rigid material, including metallic materials such as aluminum, stainless steel, and other metal alloys, or thermoplastic polymeric materials such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE). In some other embodiments, the tube portion 3060 is formed of a flexible material, including metallic materials such as nitinol, and thermoplastic polymeric materials such as polyimide. The flexible material used in the cannula portion 3060 can reduce strain on the choroid, retina and / or sclera during insertion into the cannula 3000, thereby reducing damage to the choroid, retina and / or sclera caused by insertion into the cannula 3000 during use.

[0286] Simultaneously, the funnel portion 3062 can typically be configured and shaped to facilitate the insertion and advancement of the injection cannula into the access cannula 3000. In some embodiments, the funnel portion 3062 includes a funnel-shaped or substantially funnel-shaped form. The funnel-shaped or substantially funnel-shaped form of the funnel portion 3062 facilitates the mechanical guidance of the injection cannula into the central channel 3008 during use. For example, in FIG. 30A and FIG. 30B In one embodiment, the funnel portion 3062 includes a semi-funnel shape comprising a hyperboloidal wall 3064 connected to the planar wall 3066. In such an embodiment, the hyperboloidal wall 3064 can mechanically guide the injection cannula into the central channel 3008 as it tapers proximally toward the central channel 3008. Simultaneously, the planar wall 3066 facilitates positioning the funnel portion 3062 against the outer surface of the sclera of the patient's eye. In other words, the planar wall 3066 is configured to rest flat against the outer surface of the eye, which improves the stability of the insertion cannula 3000 during use and reduces unwanted movement of the insertion cannula. In some embodiments, the planar wall 3066 can also indicate the orientation of the end face 3068 of the cannula portion 3060, thereby facilitating easier positioning and orientation of the insertion cannula after it has been inserted through the sclera. For example, the planar wall 3066 can be provided on the same or opposite side of the insertion cannula 3000 as the end face 3068 faces, and thus the user can determine the orientation of the end face 3068 by simply observing the orientation of the planar wall 3066.

[0287] In some embodiments, the funnel portion 3062 is formed of a rigid material, including metallic materials such as aluminum, stainless steel, and other metal alloys, or thermoplastic polymeric materials such as polyetheretherketone (PEEK), polyetherketone (PEK), and polytetrafluoroethylene (PTFE). In some other embodiments, the funnel portion 3062 is formed of a flexible material, including metallic materials such as nitinol, and thermoplastic polymeric materials such as polyimide. In some embodiments, the funnel portion 3062 and the tube portion 3060 may be formed of the same material, and therefore, the body 3002 may include a single integral component. However, in some other embodiments, the funnel portion 3062 and the tube portion 3060 may be formed of different materials.

[0288] FIGS. 31A-31C Schematic cross-sectional views of exemplary subretinal delivery devices 3100a, 3100b, and 3100c according to certain embodiments of this disclosure are shown. Delivery devices 3100a-c include a handle in which a fluid-driven system is integrated, which facilitates easier manipulation of the delivery devices 3100a-c during subretinal injection procedures and reduces the number of parts required for such procedures. Delivery devices 3100a-c can be used as, for example... FIG. 4 The delivery device 414 of the surgical system 400, and its aspects can be combined with other delivery devices and / or components described herein without limitation.

[0289] Turn now FIG. 31A The delivery device 3100a includes a handle 3102 and an injection cannula 3110 having a proximal end 3116 coupled to and extending distally from the distal end of the handle 3102. The injection cannula 3110 can include any suitable type of injection cannula, including those described elsewhere herein. A curved or substantially straight injection needle 3112 is disposed within the injection cannula 3110 for piercing desired ocular tissue (e.g., the retina or choroid) to deliver fluid into the subretinal space. Similar to the injection cannula 3110, the injection needle 3112 can include any suitable type of injection needle, including those described elsewhere herein. In some embodiments, the injection needle 3112 is configured to slidably extend from and retract into the distal end 3114 of the injection cannula 3110 via a toggle 3140 of the handle 3102. In some embodiments, the injection needle 3112 is coupled to an internal fluid shaft 3120 that is at least partially disposed within the cannula 3110. In such embodiments, the internal fluid shaft 3120 may be slidably disposed within the cannula 3110 to facilitate the extension and retraction of the injection needle 3112 when the actuator 3140 is actuated.

[0290] To simplify fluid preparation and delivery for subretinal injections, a fluid drive system 3160a is integrated within the handle 3102. The fluid drive system 3160a simplifies the subretinal injection procedure because an external fluid drive system (e.g., an external fluid source and pump) is no longer required to connect to the delivery device 3100a. Consequently, surgeons can focus more on the procedure and using the delivery device 3100a during the procedure without needing to worry about the setup and functionality of an external fluid drive system. This, in turn, improves the efficiency and safety of the subretinal injection procedure. Furthermore, the risk of fluid leakage or other malfunctions during subretinal injection procedures is significantly reduced without an external fluid drive system.

[0291] exist FIG. 31A In this embodiment, the fluid drive system 3160a includes an electromechanical and / or electromagnetic drive unit 3162a, one or more pistons 3164 operably coupled to the drive unit 3162a, and a cylinder 3166 configured to be operably coupled to the pistons 3164. The drive unit 3162a is configured to generate or apply force or power to the pistons 3164, which in turn causes the pistons 3164 to translate and act on the cylinder 3166 to dispense / deliver injection fluid 3168 contained in the cylinder.

[0292] The drive unit 3162a may typically include any suitable type of electromechanical and / or electromagnetic actuator for axially translating the one or more pistons 3164 within the handle 3102. For example, in some embodiments, the drive unit 3162a includes one or more electromechanical linear or rotary stepper motors. In some embodiments, the drive unit 3162a includes a rotary lead screw motor, and the piston 3164 includes a threaded slider configured to engage with the rotary lead screw. Upon receiving a control signal, the drive unit 3162a generates a mechanical rotational or linear force acting on the one or more pistons 3164 operatively coupled thereto, to axially translate the piston 3164 within the handle 3102. In some embodiments, the control signal is provided from a foot controller (e.g., foot pedal 410), surgical console (e.g., surgical console 402), or other component of the surgical system that is wired or wirelessly connected to the delivery device 3100a within the operating environment. To facilitate wireless control of the drive unit 3162a, the delivery device 3100a may further include a wireless communication module 3150, which may include a wireless transmitter and receiver circuitry to relay signals (e.g., commands) to and from the delivery device 3100a, particularly the drive unit 3162a. In some embodiments, the wireless communication module 3150 may communicate wirelessly with a foot controller or surgical console to enable remote control of the drive unit 3162a.

[0293] Cylinder 3166 includes any suitable fluid cylinder having one or more lumens 3170 that at least partially define a volume (e.g., a reservoir) for storing the injection fluid 3168. In some embodiments, cylinder 3166 includes an interchangeable and disposable cylinder pre-filled with the injection fluid 3168 before being inserted into handle 1802. In such embodiments, cylinder 3166 may include a single lumen 3170 pre-filled with a premixed solution of both therapeutic and non-therapeutic solutions, as referenced above. FIG. 16D Described as such. For example, a single lumen 3170 may include a premixed solution of a therapeutic solution (e.g., a therapeutic agent) and a non-therapeutic solution at a desired concentration / ratio. However, in other examples, the cartridge 3166 may include two or more lumens 3170 pre-filled with an unmixed solution of a therapeutic solution and / or a non-therapeutic solution. In this example, the therapeutic solution and the non-therapeutic solution can be mixed to a desired concentration / ratio within the cartridge 3166 after the cartridge 3166 is inserted into the handle and / or during injection.

[0294] When performing subretinal injection procedures using the delivery device 3100a, the pre-filled and interchangeable / disposable cartridge 3166 offers surgeons numerous advantages. For example, because the cartridge 3166 is pre-filled with all the necessary injection fluids, no additional fluid preparation is required before performing the subretinal injection procedure, and the accurate concentration / ratio of the components of the delivered injection fluid is ensured. Furthermore, this pre-filled cartridge 3166 allows surgeons to quickly decide which therapeutic substances to administer for subretinal injection based on the patient's current condition. Additionally, because therapeutic substances typically have a shorter shelf life than the delivery device, separating the cartridge 3166 from the delivery device 3100a allows surgeons to store the delivery device 3100a for a longer period without having to discard it due to the expiration of the therapeutic substance.

[0295] However, in yet another embodiment, the cylinder 3166 includes a container fixedly integrated with the handle 3102. In such an embodiment, the cylinder 3166 and the handle 3102 may include one or more ports for filling the cylinder 3166 with a therapeutic solution and a non-therapeutic solution prior to injection.

[0296] like FIG. 4As further shown, in some embodiments, a movable seal or stop 3172 is disposed at the proximal end 3174 of each lumen 3170 of the cylinder 3166 and operatively coupled to one of the one or more pistons 3164. Simultaneously, the cylinder 3166 includes a valved port 3178 at the distal end 3176 of each lumen 3170, the valved port being configured to fluidly communicate with the injection cannula 3110, the injection needle 3112, and / or the internal fluid shaft 3120. During use, axial translation of the piston 3164 distally, driven by the drive unit 3162a, causes the piston 3164 to mechanically engage the seal 3172 and push the seal distally through the lumen 3170, thereby forcing injection fluid 3168 through the valved port 3178 into the cannula 3110 (and / or the internal fluid shaft 3120) and the injection needle 3112. In some embodiments, the force of the injection fluid 3168 against the valved port 3178 causes the valved port 3178 to open to facilitate the flow of the injection fluid 3168. In some embodiments, the engagement of the cylinder 3166 with the handle 3102 upon insertion creates a puncture hole or opening in the valved port 3178 to facilitate the flow of the injection fluid 3168.

[0297] During operation of the delivery device 3100a, the user can activate and control the drive unit 3162a via the foot controller, thereby controlling the movement of the piston 3164. For example, the user can press down... FIG. 31B The foot pedal 410 described herein activates the drive unit 3162a and causes the piston 3164 to translate axially during a forward (e.g., distal) "injection" movement, thereby forcing the injection fluid 3168 out of the cylinder 3166. In some embodiments, the injection rate (e.g., output flow rate) of the injection fluid 3168 is predetermined and controlled by the drive unit 3162a. In some embodiments, the user can increase the movement of the piston 3164 by further depressing the foot pedal 410, thereby increasing the injection rate. Alternatively, reducing the pressure on the foot pedal 410 can slow the movement of the piston 3164 in the injection direction, thereby reducing the injection rate. Removing pressure from the foot pedal 410 allows it to transition to a completely unpressed state, thereby completely stopping the movement of the piston 3164 and thus stopping the injection. In some embodiments, the speed of movement of the piston 3164 and therefore the injection rate can correspond linearly to the position of the foot pedal 410.

[0298] In some embodiments, the user can also control the piston 3164 to move in a reverse (e.g., proximal) direction, thereby enabling the delivery device 3100a to aspirate fluid into the injection needle 3112 and cannula 3110 (and / or internal fluid shaft 3120). For example, the user can press a switch on the foot pedal 410 to activate the reverse mode of the delivery device 3100a, wherein subsequent pressing of the foot pedal 410 causes actuation of the piston 3164 in a proximal direction opposite to the injection direction. The reverse mode may include the same mechanical structure described above, wherein the reverse movement speed of the piston 3164 corresponds linearly to the position of the foot pedal 410.

[0299] Turn now FIG. 31B Except for certain aspects of the fluid drive system 3160b, the delivery device 3100b is substantially similar to the delivery device 3100a. For clarity, only the distinguishing aspects will be described below.

[0300] Instead of drive unit 3162a, fluid drive system 3160b includes drive unit 3162b. Similar to drive unit 3162a, drive unit 3162b is configured to generate or apply force or power to piston 3164, which in turn causes piston 3164 to translate and act on cylinder 3166 to dispense / deliver injection fluid 3168 contained in the cylinder; however, unlike drive unit 3162a, drive unit 3162b includes an electro-pneumatic actuator for axially translating the one or more pistons 3164 within handle 3102. Therefore, drive unit 3162b can be described as an electro-pneumatic actuator.

[0301] exist FIG. 31C In the exemplary embodiment depicted, the drive unit 3162b includes an electric actuator 3180, one or more fluid tanks 3184 storing pressurized fluid, and a valve 3182 disposed above and sealing an opening 3186 in each fluid tank 3184 and operatively connected to the electric actuator 3180. Examples of suitable pressurized fluids include, but are not limited to, carbon dioxide, nitrogen, and argon.

[0302] When the drive unit 3162b receives a control signal during use of the delivery device 3100b, the electric actuator 3180 can open and / or close the valve 3182 to control the flow rate of pressurized fluid through the opening 3186 and into the pressurized cavity 3188 disposed between each fluid canister 3184 and the corresponding piston 3164. In the closed state, each valve 3182 prevents any fluid from flowing into the corresponding pressurized cavity 3188. When the valve 3182 is open, pressurized fluid is allowed to flow into the pressurized cavity 3188 at a controlled flow rate depending on the position of the valve 3182. The accumulation of pressurized gas in the pressurized cavity 3188 exerts a force on the proximal side of the corresponding piston 3164, thereby causing the piston 3164 to move forward (e.g., distally) to dispense injection fluid 3168 from the canister 3166. Valve 3182 may include any suitable type of flow control valve operated by an electromechanical actuator, electromagnetic actuator, or electro-pneumatic actuator 3180. Suitable valves include, but are not limited to, solenoid valves, proportional valves, plug valves, piston valves, knife valves, etc.

[0303] Turn now FIG. 31C Except for certain aspects of the fluid drive system 3160c, the delivery device 3100c is substantially similar to the delivery devices 3100a and 3100b. For clarity, only the distinguishing aspects will be described below.

[0304] The fluid drive system 3160c includes a drive unit 3162c. Similar to the drive unit described above, the drive unit 3162c is configured to generate a force or power and apply it to a piston 3164, which in turn causes the piston 3164 to translate and act on a cylinder 3166 to dispense / deliver injection fluid 3168 contained within the cylinder; however, in FIG. 31C In this embodiment, the drive unit 3162c includes a spring actuation mechanism for axially translating the one or more pistons 3164 within the handle 3102. Therefore, the drive unit 3162c can be described as a spring-actuated driver.

[0305] exist FIG. 31C In the exemplary embodiment depicted, the drive unit 3162c includes a spring or similar device 3190 and a stop mechanism or brake 3192 operably coupled to each of the one or more pistons 3164. Each spring 3190 is disposed proximally against the corresponding piston 3164 and provides a constant biasing force against the piston 3164 in the distal direction. However, simultaneously, the stop mechanism 3192 provides a stopping force against the piston 3164 to prevent the piston 3164 from translating when biased by the spring 3190. The stopping force can be provided against the piston 3164 as a frictional force (e.g., in a laterally inward direction perpendicular to the main longitudinal axis of the handle 3102) FIGS. 32A-32D (In the middle), or the stopping force can be provided by the piston 3164 in the proximal direction.

[0306] When the drive unit 3162c receives a control signal during use of the delivery device 3100c, the stop mechanism 3192 can controllably release the corresponding piston 3164, thereby allowing the spring 3190 to actuate the piston 3164 in the distal direction and act on the cylinder 3166 to dispense the injection fluid 3168. In some embodiments, the injection rate can be controlled by reversibly adjusting the amount of stopping force provided by the stop mechanism 3192 against the piston 3164. For example, decreasing the amount of stopping force can increase the flow rate of the injection fluid 3168 from the cylinder 3166, while increasing the amount of stopping force can decrease the flow rate of the injection fluid 3168 from the cylinder 3166.

[0307] FIG. 32A A side view schematic diagram of exemplary support arms 3200a and 3200b for supporting a delivery device during a subretinal injection procedure, according to certain embodiments described herein, is shown. Support arms 3200a and 3200b can be used with any delivery device and / or delivery system as described herein without limitation.

[0308] Typically, the support arms 3200a and 3200b are configured to support or hold the delivery device during subretinal injection procedures, eliminating the need for the surgeon or other surgical team members to hold the delivery device throughout the procedure. This improves needle placement within the patient's eye and reduces unwanted movement that can occur when the delivery device is held by the user.

[0309] Looking FIG. 32A The first support arm 3200a is shown as supporting a delivery device 3210 inserted into the eye 3216 of a patient 3212. The first support arm 3200a includes a tandem arm having a plurality of hinged links 3202 connected by swivel joints 3204, which are lockable in a rotatable position. The links 3202 can generally comprise any suitable elongated rigid member, and the swivel joints 3204 can generally comprise any suitable type of lockable swivel joint, including lockable pins or toggle joints.

[0310] In the example shown, support arm 3200a includes three links 3202a-3202c, wherein link 3202a includes the nearest side link, link 3202b includes the middle link, and link 3202c includes the farthest side link. However, it is further envisioned to utilize more or fewer links 3202. For example, utilizing more links 3202 (and therefore more swivel joints 3204) could benefit support arm 3200a having more hinge points.

[0311] Links 3202a to 3202c are sequentially connected to each other via two rotary joints 3204b and 3204c: rotary joint 3204b movably connects the nearest link 3202a to the intermediate link 3202b, and rotary joint 3204c connects the intermediate link 3202b to the farthest link 3202c. The nearest link 3202a is further movably connected to the base 3206 via rotary joint 3204a, while the farthest link 3202c is movably connected to the delivery device adapter 3208 via rotary joint 3204d. Each of the rotary joints 3204a-3204d is oriented to facilitate the connection 3202a and / or the delivery device adapter 3208 around a direction parallel to... FIG. 32A The horizontal axis X is rotated along the horizontal axis of the system. Simultaneously, the base 3206 may include a lockable rotary bearing, thereby facilitating the base 3206 to rotate about a horizontal axis parallel to the system. FIG. 32B The vertical axis Y of the vertical axis rotates. Accordingly, the connecting rod 3202, the rotary joint 3204 and the base 3206 together facilitate the delivery device 3210 to have at least three degrees of freedom when connected to the delivery device adapter 3208.

[0312] FIG. 32B An enlarged side view of the delivery device adapter 3208 connected to the rotary joint 3204d is shown. As shown, the delivery device adapter 3208 includes a retainer 3230 movably connected to the guide rail 3232. The retainer 3230 includes any suitable type of gripping device configured to securely and removably grip the delivery device 3210 (in...). FIG. 32A (Seen in dashed lines). In some examples, the retainer 3230 includes a tubular or annular body through which the delivery device 3210 can be inserted and secured via friction or other locking mechanisms. In other examples, the retainer 3230 includes a clamp. In still other examples, the retainer 3230 includes a clip.

[0313] The retainer 3230 is configured to translate (e.g., slide) linearly along the guide rail 3232 in two opposite directions (indicated by arrows 3218a and 3218b), which facilitates longitudinal movement of the delivery device 3210 parallel to its main longitudinal axis A when the delivery device 3210 is coupled to the retainer. This one-dimensional translational movement of the retainer 3230 can be controlled separately from the rest of the support arm 3200a, thereby enabling fine-tuning of the longitudinal position of the delivery device 3210 when it is inserted into the eye 3216 of the patient 3212. For example, this translational movement of the retainer 3230 can be used to precisely and carefully position the injection needle of the delivery device 3210 between the RPE and the sensory retina. The translation of the retainer 3230 can be controlled by any suitable mechanism, such as a knob or similar device. In some embodiments, the retainer 3230 can be locked in place by any suitable releasable locking means after being adjusted to the desired position along the guide rail 3232.

[0314] Now return to FIG. 32A During use, the base 3206 of the support arm 3200a can be rotatably connected to the operating table 3220 (or other support structure) about a vertical axis of rotation parallel to axis Y, on which the patient 3212 lies to perform a subretinal injection procedure. Securing the support arm 3200a to the operating table 3220 improves the stability of the support arm 3200a during the subretinal injection procedure, thereby minimizing any accidental movement that may be transmitted to the delivery device 3210 (i.e., causing the delivery device to move). Accordingly, the risk of injury to the patient's eye 3216 caused by accidental movement of the delivery device 3210 is reduced, and the required level of skill to perform the procedure is lessened.

[0315] In some embodiments, the support arm 3200a is further configured to be movably rested on the head 3214 of the patient 3212 during a subretinal injection procedure. This can provide at least partial inherent compensation for head movement of the patient 3212 during the procedure, as the support arm 3200a will move with the patient's head 3214 and transmit such movement to the delivery device 3210, which is removably coupled thereto. For example, any involuntary movement of the patient's head 3214 caused by the patient's breathing can inherently be transmitted to the support arm 3200a, which then transmits that movement to the delivery device 3210. FIG. 32CIn this embodiment, the nearest lateral link 3202a is shown resting on the head 3214 of the patient 3212. In such an example, the rotary joint 3204a may not be locked in place during the subretinal injection procedure, allowing the link 3202a to move freely relative to the base 3206, which may be locked in place about its own axis of rotation. In yet another embodiment, the support arm 3200a may be used without resting on the head 3214 of the patient 3212. In such an embodiment, the rotary joint 3204a may be locked in place so that the link 3202a does not contact the patient's head 3214.

[0316] In some embodiments, to manipulate the support arm 3200a to a desired position / orientation, each link 3202 can be manually adjusted by the surgeon before performing a subretinal injection using the delivery device 3210. In some embodiments, the support arm 3200a is initially in a “locked” state, preventing rotation of the rotary joint 3204 and thus fixing the links 3202 in place. In such embodiments, to adjust the links 3202, the rotary joint 3204 must first be unlocked, allowing each link 3202 to move freely. In some examples, each rotary joint 3204 can be released independently, allowing only adjacent links 3202 to move. However, in some other examples, all rotary joints 3204 are released simultaneously via a single mechanism or action, allowing all links 3202 to move. The rotary joints 3204 can be released via any suitable mechanical or electronic mechanism. For example, in some embodiments, the rotary joint 3204 can be mechanically released via a push-push mechanism, button, locking screw, or other mechanical means provided on the support arm 3200a. In some other embodiments, the rotary joint 3204 can be released via an electromechanical locking mechanism upon receiving user input from a button or switch, foot pedal, or other user input device on the support arm 3200a. In some other embodiments, the rotary joint 3204 can be locked in place via the same or similar mechanism described above with reference to the release of the rotary joint 3204.

[0317] Typically, the manipulation of the linkage 3202 can be performed before or after the delivery device 3210 is inserted into the delivery device adapter 3208, and / or before or after the delivery device 3210 is inserted into the eye 3216 of the patient 3212. For example, in some embodiments, the delivery device 3210 is first inserted into the delivery device adapter 3208 of the support arm 3200a, then the rotary joint 3204 is released, and the linkage 3202 is manipulated to orient the attached delivery device 3210 toward the eye 3216 of the patient 3212 and into the eye. At this time, the rotary joint 3204 is locked in place, and the retainer 3230 of the delivery device adapter 3208 is finely adjusted to facilitate the insertion of the injection needle of the delivery device 3210 into the subretinal cavity. The retainer 3230 can then be locked in place, and injection fluid is subsequently delivered into the subretinal cavity via the delivery device 3210.

[0318] In some other embodiments, the delivery device 3210 is first inserted into the patient's eye 3216. Thereafter, the rotary joint 3204 of the support arm 3200a is released, and the linkage 3202 is manipulated to orient the delivery device adapter 3208 toward the delivery device 3210 already inserted into the eye 3216. At this point, the delivery device adapter 3208 is attached to the delivery device 3210. The linkage 3202 may then be finally adjusted before locking the rotary joint 3204. Afterward, the retainer 3230 of the delivery device adapter 3208 is finely adjusted and locked in place, and the injection fluid is delivered via the delivery device 3210 into the subretinal space.

[0319] In some embodiments, the linkage 3202 is configured to be manually and freely adjusted by the surgeon. In some embodiments, the linkage 3202 is configured to be adjusted via one or more knobs 3240 on each linkage 3202 or rotary joint 3204. In such embodiments, the knobs 3240 may include any suitable mechanical control mechanism for manipulating the corresponding linkage 3202, such as a button, switch, rotary knob, etc. In some embodiments, the knobs 3240 are operatively connected to, for example, one or more gears for controlling the angle and / or movement of each linkage 3202 in one or more directions. In other embodiments, the linkage 3202 may be controlled by digital knobs instead of physical knobs 3240, which are driven by an electronic controller (such as a controller communicating with a surgical console or other device including a computer). For example, the digital knobs may include digital controls provided by a computer software interface that, when adjusted by the surgeon, send signals to the electronic controller to drive manipulation of the linkage 3202 (e.g., rotation via the rotary joint 3204). In such an embodiment, the support arm 3200a may be wholly or partially a robotic arm. In such an embodiment, instead of controlling the support arm 3200a via a software interface, the support arm 3200 may be controlled via a joystick.

[0320] As described above, FIG. 32D and FIG. 32C A side view of another exemplary support arm 3200b is shown. Support arm 3200b is structurally and functionally similar to support arm 3200a, except for a few aspects discussed below.

[0321] like FIG. 32D and FIG. 32C As shown, the support arm 3200b is movably coupled to the head 3214 of the patient 3212 via a strap 3260 configured to be worn by the patient 3212. The fixation of the support arm 3200b to the patient's head 3214 provides full compensation for any head movement of the patient 3212 during the procedure, as the support arm 3200b will move / rotate with the patient's head 3214 and transmit this movement to the delivery device 3210, which is removably coupled thereto. Therefore, any involuntary movement of the patient's head 3214 caused by the patient's breathing can be directly transmitted to the support arm 3200b, which then transmits the movement to the delivery device 3210. FIG. 32D In this context, band 3260 includes a headband configured to secure the patient's head 3214 around the forehead and top of the head. FIG. 32C In the middle, band 3260 is configured to be fixed around the patient's chin 3212 and the top of the head 3214.

[0322] exist FIG. 32D andFIG. 33A In each of the figures, support arm 3200ba is coupled to belt 3260 via base 3206, which is rotatably attached to belt 3260. Further, support arm 3200b includes only two links 3202: a nearest-side link 3202d and a farthest-side link 3202e, which are movably coupled together via swivel joint 3204e. In both examples, support arm 3200b may not require as many links 3202 as a separate support arm (such as support arm 3200a) configured to support the head 3214 of patient 3212. However, even with fewer links 3202, support arm 3200b can function substantially the same as support arm 3200a. Furthermore, it is further envisioned that support arm 3200b utilize more or fewer links 3202.

[0323] FIG. 33A An exemplary operating environment 3300, such as an ophthalmic operating environment, is shown during a subretinal injection procedure according to certain embodiments of this disclosure. As described above, subretinal injection procedures are typically very delicate procedures because they require puncturing and / or manipulating one or more tissues / membranes of the eye to access the subretinal space. Accordingly, such procedures require highly skilled surgeons to minimize the risk of unnecessary damage to the patient's eye. In addition to precisely positioning the delivery device and / or other surgical instruments within the patient's eye, the surgeon must carefully control the flow rate and volume of fluid delivered to the subretinal space. Delivering too much fluid and / or delivering fluid too quickly can cause undesirable trauma to tissues on either side of the subretinal space (e.g., the retina and RPE). Conversely, delivering too little fluid (e.g., too little therapeutic material) can reduce the effectiveness of the procedure. Therefore, control of the volume and flow rate of the delivered fluid is crucial for a successful subretinal injection procedure. The following description provides systems and methods for improving the control of the volume and flow rate of fluid delivered during subretinal injection. Such systems and methods can be used in combination with delivery systems and delivery devices described elsewhere herein without limitation.

[0324] like FIG. 4 As shown, the operating environment 3300 includes a surgeon 3310, a patient 3312, and a surgical system 3302, which may represent the above-mentioned reference. FIG. 33ASurgical system 400 is described. Accordingly, surgical system 3302 includes various systems and tools, such as surgical console 3320, display device 3322, microscope system 3324, foot pedal 3326, and delivery device 3328, which may include any delivery device and / or delivery system described herein. In some embodiments, surgical system 3302 further includes a fluid drive system 3330 configured to drive the flow of injection fluid during subretinal injection and may be disposed, for example, within surgical console 3320. An example of a console configured to perform a subretinal injection procedure is the Constellation® system, available from Alcon Laboratories, Inc., Fort Worth, Texas.

[0325] The surgical console 3320 also includes a controller 3304 (shown in dashed lines) and, in some embodiments, a receiver 3306 communicating with the controller 3304. The controller 3304 is configured to (e.g., control) the surgical console 3320 to perform one or more tasks for driving a subretinal injection procedure, such as driving the flow of injection fluid via a fluid drive system 3330, based on input from the surgeon 3310 and / or stored settings and parameters associated with the procedure type, the surgeon 3310, and / or the patient 3312. In some embodiments, the controller 3304 interfaces with a digital interface of the fluid drive system 3330, which can be controlled by digital commands from the controller 3304.

[0326] Receiver 3306 may include any suitable interface for communication (e.g., one-way or two-way signaling) between controller 3304 and, for example, foot pedal 3326 and / or delivery device 3328. For example, receiver 3306 may include a wireless or wired connection between controller 3304 and foot pedal 3326 and / or delivery device 3328. In some embodiments, receiver 3306 also communicates with microphone 3332, which is configured to receive and convert voice commands from surgeon 3310 and / or other surgical team personnel into signals that are processed by controller 3304 and used to perform one or more tasks for driving the subretinal injection procedure. Although microphone 3332 is depicted on surgical console 3320, the microphone may be positioned anywhere suitable within the operating environment 3300.

[0327] exist FIG. 33BIn some embodiments, controller 3304 and receiver 3306 are integrated within surgical console 3320, wherein controller 3304 includes or refers to one or more processors and / or memory devices integrated within the surgical console. In some other embodiments, controller 3304 and / or receiver 3306 are separate devices or modules that communicate wirelessly or wiredly with surgical console 3320 and other devices, for example, within operating environment 3300. In some embodiments, controller 3304 refers to a set of software instructions that a processor associated with surgical console 3320 is configured to execute. In some aspects, the operation of controller 3304 may be performed in part by the processor associated with controller 3304 and / or surgical console 3320, and in part in a public or private cloud.

[0328] During a subretinal injection procedure, the controller 3304 interfaces (e.g., wirelessly or wiredly) with, for example, a foot pedal 3326, a delivery device 3328, and / or a fluid drive system 3330 to control various parameters associated with the fluid flow of the injected fluid. Such parameters (hereinafter referred to as “fluid flow parameters”) include fluid flow rate, fluid pressure, fluid delivery volume, fluid delivery time, and other parameters associated with the inflow or outflow of the injected fluid into the patient’s (3312) eye during the subretinal injection procedure. The fluid flow parameters may be measured directly by the fluid drive system 3330 or by a fluid flow sensor or other type of sensor separate from the fluid drive system and subsequently provided to the controller 3304. For example, in embodiments where the fluid drive system 3330 includes a motor-controlled syringe, the fluid drive system 3330 may indicate to the controller 3304 the distance the syringe plunger has shifted relative to time, or the position of the plunger relative to time, and this information may be processed by the controller 3304 to determine the various fluid flow parameters.

[0329] In some embodiments, the controller 3304 controls fluid flow parameters based on stored settings associated with the procedure type, surgeon 3310, and / or patient 3312. For example, in some embodiments, prior to a subretinal injection procedure, the surgeon 3310 may program one or more injection sequences in the controller 3304 for a specific subretinal injection procedure to be performed and / or a particular patient 3312. Such injection sequences can then be initiated during the subretinal injection procedure and may include a time series of desired fluid flow parameters. Typically, the injection sequences may include static settings of fluid flow parameters with respect to time, such as constant flow rate and / or constant fluid pressure, or dynamic settings of fluid flow parameters, such as varying flow rate and / or varying fluid pressure. Programmed injection sequences with predetermined time series of desired fluid flow parameters facilitate the surgeon 3310 in performing subretinal injection procedures accurately and precisely (i.e., repeatably). Furthermore, each subretinal injection procedure can be performed according to the specific needs of the surgeon 3310 and / or patient 3312, thereby improving the efficiency and effectiveness of each procedure. Furthermore, when the fluid is injected into the subretinal space, such an injection sequence improves volume and pressure control, thereby reducing the risk of damage to the retina and RPE.

[0330] In some embodiments, the programmed injection sequence defines various settings related to fluid flow parameters. Such settings include: maximum and / or minimum injection fluid flow rate; maximum and / or minimum injection fluid volume; maximum and / or minimum injection time; maximum and / or minimum injection fluid pressure; maximum and / or minimum rate of change between fluid flow rate, injection fluid volume, and injection fluid pressure; number, time, and / or sequence of injection phases, etc.

[0331] In some embodiments, one or more programmed injection sequences can be simultaneously or sequentially selected, activated, and / or deactivated by the surgeon 3310 (and / or other surgical team members) via inputs received from the surgeon 3310 (and / or other surgical team members) via the foot pedal 3326, delivery device 3328, and / or microphone 3332. For example, in such embodiments, the inputs may include manipulation of hand-actuated controls (such as buttons or other toggles) on the delivery device 3328 by the surgeon 3310, and / or manipulation of foot-actuated controls (such as foot pedals) on the foot pedal 3326. In some examples, the inputs may include voice commands received from the surgeon 3310 via the microphone 3332. Utilizing voice commands for fluid flow control can facilitate easier manipulation of the delivery device 3328 and / or other surgical instruments during subretinal procedures, as the surgeon 3310 does not require additional motor coordination to adjust or control fluid flow parameters. Accordingly, the surgeon 3310 can focus their full attention on keeping the delivery device 3328 stationary during injection.

[0332] Signals corresponding to inputs on delivery device 3328, foot pedal 3326, and / or microphone 3332 are received by receiver 3306 and transmitted to controller 3304. The controller then takes one or more actions to control the flow of fluid by fluid drive system 3330 based on inputs from surgeon 3310 (and / or other surgical team members) and a programmed injection sequence. In some embodiments, inputs from surgeon 3310 are mapped by controller 3304 to corresponding injection sequences, fluid flow parameters, and / or actions to be performed by fluid drive system 3330 and / or surgical console 3320. Controller 3304 then configures and drives fluid drive system 3330 and / or surgical console 3320 to perform such injection sequences, fluid flow parameters, and / or actions. In some embodiments, the injection sequence being taken or to be taken, fluid flow parameters, and / or actions are displayed to surgeon 3310 on display device 3322.

[0333] In some embodiments, the programmed injection sequence includes a user-programmed (e.g., surgeon-programmed) injection sequence programmed prior to performing a subretinal injection procedure. In some embodiments, in addition to or replacing the injection sequence programmed by surgeon 3310, the controller may include one or more pre-programmed and generic injection sequences and / or other settings associated with the subretinal injection procedure. Such pre-programmed and generic sequences may include injection sequences generally applicable to most subretinal injection procedures and may be provided (e.g., programmed) by the manufacturer of one or more components of surgical system 3302 during manufacturing or assembly. In such embodiments, during the procedure, input from surgeon 3310 is mapped by controller 3304 to a corresponding pre-programmed and generic injection sequence and / or other settings to be performed by fluid drive system 3330 and / or surgical console 3320, after which controller 3304 configures and drives fluid drive system 3330 and / or surgical console 3320 to perform according to such pre-programmed and generic injection sequences and / or other settings.

[0334] In some embodiments utilizing programmed or pre-programmed injection sequences, controller 3304 includes protective measures for aborting the flow of injection fluid driven by fluid drive system 3330 during an active injection sequence. For example, in some embodiments, controller 3304 may be programmed to require continuous manual input from surgeon 3310 to continue or execute the active injection sequence. In other words, controller 3304 may include a “death switch” that stops the execution of the injection procedure in the absence of input from surgeon 3310. Continuous manual input may include continuous manipulation of one or more foot-actuated controls on foot pedal 3326 and / or continuous manipulation of one or more hand-actuated controls on delivery device 3328. For example, to initiate and execute the injection sequence to completion, surgeon 3310 may be required to press down the footplate on foot pedal 3326 throughout the injection sequence. Accordingly, if any problem occurs during the injection sequence, surgeon 3310 may release the footplate, thereby immediately stopping the injection sequence. In such an example, using foot pedal 3326 instead of another device in the operating environment 3300 as a death switch can reduce any unnecessary visual distractions for the surgeon 3310 during the injection procedure, and the surgeon 3310 can better focus their visual attention on the patient 3312’s eyes and their manipulation of the delivery device 3328 therein.

[0335] In another embodiment, controller 3304 may control fluid flow parameters entirely or partially based on real-time input from surgeon 3310 (and / or other surgical team members), thereby enabling fully manual control of the subretinal injection procedure. Similarly, as described above, input may include manipulation of hand-actuated controls on delivery device 3328 and / or foot-actuated controls on foot pedal 3326 by surgeon 3310. In such examples, the degree or level of manipulation of the hand or foot actuation controls (e.g., the degree or amount of pressure) may correspond to the magnitude of the fluid flow parameters. For example, pressing the hand or foot actuation controls further may result in an increase in fluid flow rate, fluid pressure, and / or fluid delivery volume, while reducing the pressure (or releasing) of the hand or foot actuation controls may result in a decrease in fluid flow rate, fluid pressure, and / or fluid delivery volume. In some examples, input may include voice commands received from surgeon 3310 via microphone 3332.

[0336] Signals corresponding to inputs on delivery device 3328, foot pedal 3326 and / or microphone 3332 are received by receiver 3306 and transmitted to controller 3304, which then takes one or more actions to drive fluid drive system 3330 based on inputs from surgeon 3310 (and / or other surgical team members).

[0337] In some embodiments, during a subretinal injection procedure, the surgical system 3302 may provide visual and / or auditory feedback to the surgeon 3310 and / or other surgical team personnel regarding fluid flow parameters and the progress of the procedure. For example, in some embodiments, measurements of fluid flow parameters (expressed in volume units (e.g., µL) or volume percentages (e.g., %)) and / or the status or progress of the injection sequence may be displayed continuously or periodically on the screen of the display device 3322 and / or the screen or eyepiece of the microscope system 3324. In some embodiments, the surgical system 3302 may include a speaker 3334 for providing the surgeon 3310 with periodic auditory indications regarding fluid flow parameters and / or the progress of the procedure. In such embodiments, auditory indications can facilitate easier manipulation of the delivery device 3328 and / or other surgical instruments during a subretinal procedure because the number of visual distractions during the procedure is reduced or limited. Accordingly, the surgeon 3310 can focus their full visual attention on keeping the delivery device 3328 stationary during the injection. Examples of suitable auditory cues include both speech and non-speech sounds. When using non-speech sounds, the type, frequency, amount, or pitch of the non-speech sound can indicate different parameters and / or states of a subretinal injection procedure. In some embodiments, auditory cues can be provided periodically during predefined intervals based on the time or volume of the injected fluid. Such auditory cues can indicate measurements of fluid flow parameters as volume units (e.g., µL) or volume percentages (e.g., %).

[0338] FIG. 33A The various components of the operating environment 3300 are shown. FIGS. 34A-34DThe diagram illustrates how the surgical system 3302 (shown in the figure) communicates and operates together. As shown, the surgical console 3320 of the surgical system 3302 includes, but is not limited to, a controller 3304 and a receiver 3306, enabling the controller 3304 to connect to a foot pedal 3326, a delivery device 3328, and / or a fluid drive system 3330. The controller 3304 includes an interconnect 3360 and a network interface 3362 for connection to a data communication network 3364. The controller 3304 further includes a central processing unit (CPU) 3366, a memory 3368, and a storage device 3370. The CPU 3366 can retrieve application data and store it in the memory 3368, as well as retrieve and execute instructions stored in the memory 3368. The interconnect 3360 transmits instructions and application data, such as instructions related to the control of fluid flow parameters, between the CPU 3366, the network interface 3362, the memory 3368, the storage device 3370, the delivery device 3328, the fluid drive system 3330, etc. CPU3366 can represent a single CPU, multiple CPUs, or a single CPU with multiple processing cores. Memory 3368 can represent random access memory.

[0339] Storage device 3370 may be a disk drive. Although shown as a single unit, storage device 3370 may be a combination of fixed or removable storage devices, such as a fixed disk drive, a removable memory card or optical storage device, a network-attached storage device (NAS), or a storage area network (SAN). Storage device 3370 may include user-programmed subretinal injection procedure parameters / settings 3372, such as a user-programmed injection sequence 3374. Storage device 3370 may further include pre-programmed subretinal injection procedure parameters / settings 3376, such as a pre-programmed generic injection sequence 3378. Each of the user-programmed injection sequence 3374 and the pre-programmed generic injection sequence 3378 may include preset instructions for controlling fluid flow parameters driven by fluid drive system 3330.

[0340] Meanwhile, the memory 3368 includes an operating system 3380 and / or one or more applications that, when executed by the CPU 3366, allow the controller 3304 to configure and operate the surgical console 3320 (e.g., including a fluid drive system 3330 based on retrieved subretinal injection procedure parameters / settings).

[0341] FIG. 34AA cross-sectional view of a portion of an eye 3400 is shown at different steps of an exemplary subretinal injection procedure with post-injection sealing, according to certain embodiments of this disclosure. During and after the injection of fluid into the subretinal space at the target injection site, some leakage or spillage of non-therapeutic and / or therapeutic solutions may occur through the target injection site. This is generally undesirable because any escape of therapeutic material reduces the effectiveness of the procedure and may also increase the risk of unintended complications from contact of therapeutic material with non-target eye tissues. Therefore, as discussed elsewhere herein, when fluid is delivered into the subretinal space at the target injection site, the target injection site may be filled with a sealant to prevent the injected fluid from escaping the subretinal space. The following description includes an example of performing such a sealing procedure after subretinal delivery of fluid using the transvitreal approach. Although the transvitreal approach is described, aspects of the following methods can be applied using the suprachoroidal approach.

[0342] Turn now FIGS. 34B-34D Subretinal injections can be performed using any suitable delivery device and / or system described herein. For example, the injection cannula 3510 of the delivery device can be inserted through a valved insertion cannula (or other access cannula) that passes through a scleral incision site in the eye 3400 and is guided through the vitreous cavity 3412 toward the retina 3404. The injection cannula 3510 of the delivery device is guided through the vitreous cavity 3412 until its distal end 3514 is positioned at a target injection site 3406 adjacent to the surface of the retina 3404. Once in place, the injection needle 3512 of the delivery device can extend and / or insert through the target injection site 3406 and into the subretinal space 3424, for example, between the outermost neural layer and the retinal pigment epithelium (RPE) 3408 of the retina 3404, to inject fluid 3418 into the subretinal space 3424. Afterward, the injection needle 3512 can be retracted into the cannula 3510, and the cannula 3510 is removed from the eye 3400 through the valved insertion cannula.

[0343] At this point, any of a variety of sealing modes can be used to seal the target injection site 3406. FIG. 34B Various sealing modalities that can be used in conjunction with subretinal injection procedures were demonstrated.

[0344] like FIG. 34CAs shown, in some embodiments, a suitable application device (such as tweezers 3442) is used to apply the graft 3440 to the target injection site 3406. For example, tweezers 3442 can be used to grasp the graft 3440 and insert it into the eye 3400 (e.g., through a valved cannula or another access cannula inserted into the sclera), and then the graft 3440 is positioned on the target injection site 3406 and flattened so that the graft seals the target injection site 3406.

[0345] In some embodiments, graft 3440 includes a biological graft or scaffold, such as a cell graft. In some embodiments, graft 3440 includes a human amniotic membrane (hAM) graft. The amniotic membrane is the innermost layer of the placenta and consists of a non-adhesive basement membrane, a thick intermediate collagen layer, and an adhesive avascular matrix. For sealing purposes, the adhesive matrix of the amniotic membrane can be placed “face down” on the surface of the retina 3404 to adhere to the retina 3404 and seal the target injection site 3406. Other examples of biological scaffolds or cell grafts that can be utilized include scaffolds or grafts containing retinal cells, such as iPSC-derived retinal cells.

[0346] In some embodiments, the graft 3440 includes a polymer-based scaffold, such as a polymer nanofiber scaffold.

[0347] Turn now FIG. 34D As an alternative to grafts, a suitable application device (such as injector 3452) can be used to apply the sealing solution 3450 to the target injection site 3406. In some embodiments, the sealing solution 3450 may include one or more human proteins and / or cell adhesion factors in the solution, which can be injected at the target injection site 3406 to seal the target injection site 3406. Examples of usable proteins and adhesion factors include fibrin, collagen, thrombin, fibronectin, laminin, and other proteins and / or adhesion factors that promote coagulation and / or adhesion. After injection, the proteins and / or adhesion factors can be naturally broken down in the body through the patient's own catabolic pathways / processes.

[0348] In some embodiments, the sealing solution 3450 comprises a polymer that can be naturally degraded in vivo through the patient's own catabolic pathways / processes. For example, in some embodiments, the sealing solution 3450 may comprise a polymeric hydrogel, such as a biopolymer. Examples of biopolymers that can be utilized include chitosan, hyaluronic acid, gelatin, alginate, methylcellulose, and collagen.

[0349] FIG. 34D This demonstrates yet another alternative sealing mode. In ​In this embodiment, the target injection site 3406 in the retina 3404 is sealed by a laser probe 3460 via photocoagulation. The laser probe 3460 can therefore comprise any suitable type of retinal therapeutic laser probe operatively coupled to a laser source for generating and propagating a laser beam with a wavelength between about 400 nm and about 850 nm. For example, the laser probe 3460 can be operatively coupled to an Nd-YAG laser source. Accordingly, the laser probe 3460 can be used to emit a laser beam 3462 to the target injection site 3406, which can ablate and seal the retina 3404 at the target injection site 3406, thereby preventing any previously delivered therapeutic material from escaping.

[0350] In summary, the embodiments disclosed herein improve the efficacy and safety of subretinal injections for the treatment of ophthalmic conditions.

[0351] As used herein, the phrase “at least one” in the list of items refers to any combination of these items, including a single member. For example, “at least one of a, b, or c” is intended to cover a, b, c, ab, ac, bc, and abc, as well as any combination of multiples of the same element (e.g., aa, aaa, aab, aac, abb, acc, bb, bbb, bbc, cc, and ccc, or any other order of a, b, and c).

[0352] The foregoing description is provided to enable any person skilled in the art to practice the various embodiments described herein. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be applied to other embodiments. Therefore, the claims are not intended to limit them to the embodiments shown herein, but are given the full scope consistent with the language of the claims.

[0353] In the claims, unless specifically stated otherwise, references to singular elements are not intended to mean “one and only one” but rather “one or more”. Unless otherwise specifically stated otherwise, the term “some” means one or more. All structural and functional equivalents of elements in all aspects described throughout this disclosure that are known or will be known hereafter by one of ordinary skill in the art are expressly incorporated herein by reference and are intended to be covered by the claims. Furthermore, nothing disclosed herein is intended for public disclosure, whether or not such disclosure is expressly stated in the claims. Pursuant to 35 USC §112(f), no element of any claim will be construed unless it is expressly stated using the phrase “means for…” or, in the case of a method claim, using the phrase “steps for…”. The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any aspect described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects. Example Implementation

[0354] Example 1: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including: a first lumen disposed therein; and an actuable actuating element movably coupled to a handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; and a needle movably disposed within the second lumen and coupled to the actuating actuating element, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the actuating element is actuated.

[0355] Example 2: The surgical instrument as described in Example 1, wherein the needle includes a curved needle, and wherein the curvature of the needle increases as the needle extends out of the second lumen, and wherein the curvature of the needle decreases as the needle retracts into the second lumen.

[0356] Example 3: The surgical instrument as described in Example 2, wherein the needle is formed of an elastic material.

[0357] Example 4: The surgical instrument as described in Example 1 further includes an annular insert disposed in a second lumen at the distal end of the cannula. The annular insert is connected to at least a portion of the needle inside and outside the second lumen. The needle extends from the second lumen and passes through the annular insert, increasing the flexibility of the needle. The needle retracts into the second lumen and passes through the annular insert, increasing the rigidity of the needle.

[0358] Example 5: The surgical instrument as described in Example 1, wherein the needle includes: a first proximal portion having a first outer diameter; and a second distal portion having a second outer diameter.

[0359] Example 6: The surgical instrument as described in Example 5, wherein the first proximal portion has a size of 38 or smaller, and wherein the second distal portion has a size of 37 or larger.

[0360] Example 7: The surgical instrument as described in Example 5, wherein the first proximal portion has a size of 41 or smaller, and wherein the second distal portion has a size of 40 or larger.

[0361] Example 8: The surgical instrument as described in Example 1, wherein the needle includes a beveled distal end, the beveled distal end including a distal end face set at a non-right angle and a non-zero angle relative to the main longitudinal axis of the needle.

[0362] Example 9: The surgical instrument as described in Example 8, wherein the needle further includes a port disposed in its sidewall and adjacent to the obliquely cut distal end.

[0363] Example 10: The surgical instrument as described in Example 1, wherein the needle includes an annular sealing element externally connected to a portion of the needle at the distal end of the needle.

[0364] Example 11: The surgical instrument as described in Example 1, wherein the needle includes a polymer coating formed on its inner wall, the polymer coating being used to reduce fluid resistance through the cannula.

[0365] Example 12: The surgical instrument as described in Example 11, wherein the polymer coating is further disposed on the inner wall of the cannula.

[0366] Example 13: The surgical instrument as described in Example 11, wherein the polymer coating comprises at least one of the following: poly(ethylene oxide) (PEO), poly(methyl methacrylate) (PMMA), poly(hydroxyethyl methacrylate) (PHEMA), polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), perfluoroalkoxy (PFA), trifluorochloroethylene (E-CTFE), or polyether ether ketone (PEEK).

[0367] Example 14: The surgical instrument as described in Example 1, wherein the actuating actuator is lockable, so that the needle can be fixed in the extended position or the retracted position.

[0368] Example 15: The surgical instrument as described in Example 1 further includes: a first flexible conduit, the first flexible conduit being fluidly connected in a first lumen at the distal end of the first flexible conduit to an actuable actuator or needle, the first flexible conduit being further fluidly connected in a proximal end of the first flexible conduit to a connector disposed at the proximal end of a handpiece, wherein the connector is further configured to be fluidly connected in a second flexible conduit outside the first lumen.

[0369] Example 16: The surgical instrument as described in Example 15 further includes: a second flexible conduit fluidly connected to a connector outside the first lumen.

[0370] Example 17: The surgical instrument as described in Example 1, wherein the actuable actuating element is arranged around the circumference of the handheld element.

[0371] Example 18: The surgical instrument as described in Example 1, wherein the actuable actuating element includes a plurality of actuating elements externally attached to a portion of the handpiece.

[0372] Example 19: A surgical instrument as described in Example 1, wherein the handpiece is configured to removably receive a cartridge pre-filled with injection fluid, wherein the cartridge is fluidly connected to a cannula or needle for injection of the injection fluid.

[0373] Example 20: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including: a first lumen disposed therein; and an actuable actuating element movably coupled to a handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; and a needle movably disposed within the second lumen and coupled to the actuating actuating element, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the actuating element is actuated.

[0374] Example 21: The surgical instrument as described in Example 20, wherein at least a portion of the cannula is formed of a flexible metal or thermoplastic material.

[0375] Example 22: The surgical instrument as described in Example 21, wherein another portion of the cannula is formed of a rigid material.

[0376] Example 23: Surgical instruments as described in Example 20, wherein the cannula has an elliptical, pill-shaped, or crescent-shaped cross-sectional profile.

[0377] Example 24: The surgical instrument as described in Example 20, wherein the cannula includes a pre-shaped curvature along the length of the cannula.

[0378] Example 25: The surgical instrument as described in Example 20, wherein the cannula further includes a distal tip, the distal tip including a distal portion having a semi-circular disc shape for stratifying tissue when inserted into the eye.

[0379] Example 26: The surgical instrument as described in Example 25, wherein the distal end further includes a proximal portion having a port through which a needle can extend from and retract into the second lumen.

[0380] Example 27: The surgical instrument as described in Example 26, wherein the proximal portion of the distal end further includes an inclined surface disposed adjacent to the port, and the needle is configured to slide along the inclined surface as it extends and retracts through the port.

[0381] Example 28: The surgical instrument as described in Example 20, wherein the cannula further includes a distal tip formed of a photoluminescent material.

[0382] Example 29: The surgical instrument as described in Example 28, wherein the cannula further includes a distal tip formed of a phosphorescent material.

[0383] Example 30: The surgical instrument as described in Example 20, wherein the cannula further includes a distal end having a scraper portion and a body portion, wherein the thickness of the distal end increases between the scraper portion and the body portion to form a ramp for stratifying tissue when inserted into the eye.

[0384] Example 31: The surgical instrument as described in Example 30, wherein the main body includes a port through which a needle can extend from and retract into the second lumen.

[0385] Example 32: The surgical instrument as described in Example 31, wherein the main body portion of the distal end further includes an inclined surface disposed adjacent to the port, and the needle is configured to slide along the inclined surface as it extends and retracts through the port.

[0386] Example 33: The surgical instrument as described in Example 20 further includes an optical fiber that extends along the cannula and has a termination end at or near the distal end of the cannula, the optical fiber being configured to emit light from the termination end.

[0387] Example 34: The surgical instrument as described in Example 33, wherein the optical fiber includes a single-core or multi-core optical fiber configured to propagate white light.

[0388] Example 35: The surgical instrument as described in Example 20, wherein the cannula further includes a distal end having a port through which a needle can extend from and retract into the second lumen, the port being disposed adjacent to an inclined surface for guiding the needle through the port as it extends from and retracts into the second lumen.

[0389] Example 36: A surgical instrument as described in Example 35, wherein the proximal end of the needle is coupled to a slider configured to slide along the inclined surface as the needle extends and retracts through the port.

[0390] Example 37: The surgical instrument as described in Example 36, wherein at least one of the slider and the inclined surface is formed of a material comprising at least one of the following: steel, titanium, PEEK (polyether ether ketone), polyoxymethylene (POM), and polytetrafluoroethylene (PTFE).

[0391] Example 38: The surgical instrument as described in Example 20, wherein the cannula further includes a port through which a needle can extend from and retract into the second lumen, the port being disposed in the side wall of the cannula, and wherein the distal portion of the needle includes a plug-drill shape such that the needle can extend and retract through the port as the needle rotates.

[0392] Example 39: The surgical instrument as described in Example 38, wherein the needle tip is curled along a plane perpendicular to the main longitudinal axis of the needle tip to form a plug-drill shape.

[0393] Example 40: The surgical instrument as described in Example 20, wherein the cannula further includes a distal end comprising: a first port disposed in a sidewall of the distal end through which a needle can extend from and retract into a second lumen, the port being disposed adjacent to an inclined surface for guiding the needle through the port as it extends from and retracts into the second lumen; and a second port disposed in a distal surface for injecting fluid along a flow path parallel to or substantially parallel to the main longitudinal axis of the distal end.

[0394] Example 41: The surgical instrument as described in Example 40, wherein the second port is fluidly connected to a fluid conduit disposed within the cannula.

[0395] Example 42: The surgical instrument as described in Example 20, wherein the cannula further includes a third lumen extending through at least a portion of the length of the cannula, the third lumen being configured to removably receive a wire through a port disposed in the distal end of the cannula or in the side wall of the cannula.

[0396] Example 43: The surgical instrument as described in Example 42, wherein the filament is configured to increase the stiffness of the cannula for insertion into the eye.

[0397] Example 44: The surgical instrument as described in Example 42, wherein the filament is configured to facilitate guiding the cannula to the target injection site when inserted into the eye.

[0398] Example 45: A support system for a fluid injection device, the support system comprising: a support arm including: a base configured to rotate about its axis; a plurality of hinged links movably connected to the base; a device adapter movably connected to at least one of the plurality of hinged links, the device adapter being configured to secure the fluid injection device; and a plurality of rotary joints movably connecting the at least one of the plurality of hinged links to the device adapter, movably connecting adjacent links of the plurality of hinged links, and movably connecting at least another link of the plurality of hinged links to the base.

[0399] Example 46: Surgical instrument as described in Example 45, wherein the base is rotatably connected to a strap configured to be placed around the patient's head.

[0400] Example 47: Surgical instrument as described in Example 45, wherein the base is rotatably connected to an operating table or other support structure configured to support the patient's head.

[0401] Example 48: The surgical instrument as described in Example 47, wherein the base is configured to rotate about a vertical axis, and wherein at least one of the plurality of rotary joints is configured to rotate about a horizontal axis perpendicular to the vertical axis.

[0402] Example 49: The surgical instrument as described in Example 47, wherein at least one of the plurality of articulated links is configured to rest against the patient’s head during use.

[0403] Example 50: The surgical instrument as described in Example 45, wherein the plurality of articulated links comprises a series of articulated links.

[0404] Example 51: The surgical instrument as described in Example 45, wherein the support arm provides at least three degrees of freedom for the fluid injection device.

[0405] Example 52: The surgical instrument as described in Example 45, wherein at least one of the plurality of rotary joints is lockable in rotational orientation.

[0406] Example 53: The surgical instrument as described in Example 45, wherein the base is lockable in rotational orientation.

[0407] Example 54: The surgical instrument as described in Example 45, wherein the device adapter includes a fluid injection device holder movably coupled to a guide rail.

[0408] Example 55: The surgical instrument as described in Example 54, wherein the fluid injection device holder includes a clamp or clip for securing the fluid injection device.

[0409] Example 56: The surgical instrument as described in Example 54, wherein the fluid injection device holder includes a tubular or annular body for securing the fluid injection device.

[0410] Example 57: The surgical instrument as described in Example 54, wherein the fluid injection device holder includes a tubular or annular body for securing the fluid injection device.

[0411] Example 58: The surgical instrument as described in Example 54, wherein the fluid injection device holder is configured to translate linearly along the guide rail, thereby facilitating both rotational and translational movement of the fluid injection device when connected to the device adapter.

[0412] Example 59: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including a first lumen disposed therein; at least one actuable actuator movably coupled to a handle; a hinged cannula coupled to the handpiece and configured for insertion into an eye, the hinged cannula including a second lumen extending therethrough, the hinged cannula being configured to hinge when the at least one actuable actuator is actuated; and a needle movably disposed within the second lumen and coupled to the at least one actuable actuator, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the at least one actuable actuator is actuated.

[0413] Example 60: The surgical instrument as described in Example 59, wherein the articulated cannula includes one or more features etched or cut into the outer surface of the articulated cannula to facilitate its articulation.

[0414] Example 61: The surgical instrument as described in Example 60, wherein the articulated cannula is formed of at least one of the following: aluminum, stainless steel, polyether ether ketone (PEEK), polyether ketone (PEK), or polytetrafluoroethylene (PTFE).

[0415] Example 62: The surgical instrument as described in Example 59 further comprises: one or more wires connected at one end to the at least one actuable actuator and at the other end in a second lumen to one or more points along the length of the articulated cannula, wherein actuation of the at least one actuable actuator causes the wire to act on the articulated cannula and manipulate the curvature of the articulated cannula.

[0416] Example 63: The surgical instrument as described in Example 59, wherein the at least one actuable actuating element includes a first actuating element for extending and retracting a needle from and from a second lumen, and a second actuating element for manipulating a hinged cannula.

[0417] Example 64: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including a first lumen disposed therein; at least one actuable actuator movably coupled to a handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; a reinforcing sleeve disposed around the cannula and configured to translate along the length of the cannula when the at least one actuable actuator is actuated, wherein distal translation of the reinforcing sleeve increases the stiffness of the cannula, and proximal translation of the reinforcing sleeve decreases the stiffness of the cannula; and a needle movably disposed within the second lumen and coupled to the at least one actuable actuator, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the at least one actuable actuator is actuated.

[0418] Example 65: The surgical instrument as described in Example 64, wherein the reinforcing sleeve comprises a hollow tubular body.

[0419] Example 66: The surgical instrument as described in Example 65, wherein the reinforcing sleeve is formed of a metallic material comprising at least one of the following: stainless steel, aluminum, or titanium.

[0420] Example 67: The surgical instrument as described in Example 65, wherein the reinforcing sleeve is formed of a composite material comprising at least one of the following: polyether ether ketone (PEEK), polyether ketone (PEK), polytetrafluoroethylene (PTFE), or polycarbonate (PC).

[0421] Example 68: The surgical instrument as described in Example 64, wherein the position of the reinforcing sleeve along the length of the cannula is releasably locked.

[0422] Example 69: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including a first lumen disposed therein; at least one actuable actuator movably coupled to the handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; a reinforcing sleeve disposed within the cannula and configured to translate along the length of the cannula when the at least one actuable actuator is actuated, wherein distal translation of the reinforcing sleeve increases the stiffness of the cannula, and proximal translation of the reinforcing sleeve decreases the stiffness of the cannula; and a needle movably disposed within the second lumen and coupled to the at least one actuable actuator, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the at least one actuable actuator is actuated.

[0423] Example 70: The surgical instrument as described in Example 69, wherein the reinforcing sleeve comprises a hollow tubular body.

[0424] Example 71: The surgical instrument as described in Example 70, wherein the reinforcing sleeve is formed of a metallic material comprising at least one of the following: stainless steel, aluminum, or titanium.

[0425] Example 72: The surgical instrument as described in Example 70, wherein the reinforcing sleeve is formed of a composite material comprising at least one of the following: polyether ether ketone (PEEK), polyether ketone (PEK), polytetrafluoroethylene (PTFE), or polycarbonate (PC).

[0426] Example 73: The surgical instrument as described in Example 69, wherein the position of the reinforcing sleeve along the length of the cannula is releasably locked.

[0427] Example 74: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece including a first lumen disposed therein; at least one actuable actuator movably coupled to a handle; a cannula indirectly coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; a needle movably disposed within the second lumen and coupled to the at least one actuable actuator, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the actuable actuator is actuated; and a shaft adapter connecting the cannula to the handpiece, the shaft adapter including a curvature such that at least a portion of the main longitudinal axis of the cannula is not parallel to the main longitudinal axis of the handpiece.

[0428] Example 75: The surgical instrument as described in Example 74, wherein the shaft adapter includes a curved hollow tubular body.

[0429] Example 76: The surgical instrument as described in Example 74, wherein the cannula is configured to extend from and retract into the distal end of the shaft adapter when the at least one actuable actuator is actuated.

[0430] Example 77: The surgical instrument as described in Example 74, wherein the shaft adapter is formed of a metallic material including at least one of the following: stainless steel, aluminum, or titanium.

[0431] Example 78: A surgical instrument as described in Example 74, wherein the shaft adapter has a radius of curvature between about 1 mm and about 20 mm.

[0432] Example 79: An access cannula for inserting surgical instruments into the eye, the access cannula comprising: a hollow body including a distal end, a proximal end, and a central channel extending from the distal end to the proximal end, wherein the hollow body includes a non-circular cross-sectional profile; a distal portion disposed at the distal end of the hollow body, the distal portion including a wedge shape; and a proximal portion disposed at the proximal end of the hollow tubular body, the proximal portion including a tubular shape.

[0433] Example 80: The insertion cannula as described in Example 79, wherein the hollow body includes a flat cross-sectional profile having an elliptical, oval, or pill-shaped form.

[0434] Example 81: Insertion cannula as described in Example 79, wherein the distal portion includes a cut formed in the sidewall of the hollow body.

[0435] Example 82: Insertion cannula as described in Example 79, wherein the distal and proximal portions are formed of the same material.

[0436] Example 83: Insertion cannula as described in Example 79, wherein the distal and proximal portions are formed of different materials.

[0437] Example 84: The insertion cannula as described in Example 79 further includes one or more fixation arms connected to and extending laterally from the proximal portion, the one or more fixation arms being used to secure the insertion cannula when inserted into the eye.

[0438] Example 85: Insertion cannula as described in Example 84, wherein the one or more fixation arms are rigidly connected to the proximal portion.

[0439] Example 86: The cannulation as described in Example 84, wherein the one or more fixation arms are extendably coupled to the proximal portion such that the one or more fixation arms can extend laterally outward from the proximal portion and retract laterally inward toward the proximal portion.

[0440] Example 87: An access cannula for inserting surgical instruments into the eye, the access cannula comprising: a tube portion including a distal end and a proximal end and a central channel extending from the distal end to the proximal end, the tube portion further including an end face disposed at the distal end and oriented in a wedge shape at a non-right angle relative to the main longitudinal axis of the tube portion; and a funnel portion connected to the proximal end of the tube portion, the funnel portion having a funnel shape to facilitate insertion of surgical instruments into the tube portion.

[0441] Example 88: The insertion cannula as described in Example 87, wherein the funnel portion comprises a semi-funnel shape formed by a hyperboloidal wall connected to a planar wall.

[0442] Example 89: Insertion cannula as described in Example 88, wherein the position of the planar wall of the funnel portion corresponds to the orientation of the end face of the tube portion.

[0443] Example 90: A surgical instrument for fluid injection, the surgical instrument comprising: a handpiece configured for gripping by a user, the handpiece being formed of a lightweight thermoplastic material and including a first lumen disposed therein; an actuable actuator movably coupled to a handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough; and a needle movably disposed within the second lumen and coupled to the actuable actuator, the needle being configured to extend from and retract into the second lumen at a distal end of the cannula when the actuable actuator is actuated, wherein the surgical instrument is configured to hang freely without damaging the eye when inserted into the eye.

[0444] Example 91: The surgical instrument as described in Example 90, wherein the lightweight thermoplastic material includes at least one of the following: polyether ether ketone (PEEK), polyether ketone (PEK), or polytetrafluoroethylene (PTFE).

[0445] Example 92: The surgical instrument as described in Example 90, wherein the actuating element includes a sliding button.

[0446] Example 93: The surgical instrument as described in Example 90, wherein the handpiece includes a fastening device disposed on its outer surface for securing the surgical instrument to the patient.

[0447] Example 94: The surgical instrument as described in Example 93, wherein the fastening device includes a Velcro strip.

[0448] Example 95: A system for administering an injection into the subretinal space of the eye, the system comprising: an expandable guiding cannula for traversing the suprachoroidal space of the eye, the expandable guiding cannula including: a flexible tubular member configured to expand laterally; and a first channel extending from a proximal end to a distal end of the flexible tubular member, wherein the lateral expansion of the flexible tubular member increases the lateral dimension of the first channel to facilitate the entry of an injection cannula through the expandable guiding cannula; an injection cannula configured to pass through the first channel, the injection cannula including a lumen at least partially extending therethrough; and a needle movably disposed within the lumen, the needle being configured to extend from and retract into the lumen at a distal end of the injection cannula.

[0449] Example 96: The system as described in Example 95, wherein the flexible tubular member further includes a second channel disposed within its sidewall, and wherein the flexible tubular member expands by filling the second channel with a working fluid.

[0450] Example 97: The system as described in Example 95, wherein the expandable guide cannula further includes a hub configured to contact the surface of the eye and anchor the expandable guide cannula.

[0451] Example 98: The system as described in Example 97, wherein the hub includes a port for filling a portion of the flexible tubular member with a working fluid to cause the flexible tubular member to expand.

[0452] Example 99: The system as described in Example 97, wherein the hub has an inclined inner surface for mechanically guiding the injection cannula during insertion into an expandable guide cannula.

[0453] Example 100: The system as described in Example 95, wherein the flexible tubular body is formed of at least one of the following: silicone, polyurethane (PUR), polyether block amide (PEBA), or polyolefin.

[0454] Example 101: The system as described in Example 100, wherein the hub is formed of the same material as the flexible tubular body.

[0455] Example 102: The system as described in Example 100, wherein the hub is formed of a rigid or non-expandable material.

[0456] Example 103: The system as described in Example 95, wherein a flexible tubular member is connected to braided filaments, and wherein the flexible tubular member expands by twisting the braided filaments.

[0457] Example 104: A surgical system for fluid injection, the surgical system comprising: an injection device including: a handpiece configured for gripping by a user, the handpiece including a first lumen disposed therein; an actuable actuator movably coupled to the handle; a cannula coupled to the handpiece and configured for insertion into an eye, the cannula including a second lumen extending therethrough and a distal end at a distal end of the cannula; and a needle movably disposed within the second lumen and coupled to the actuable actuator, the needle being...

Claims

1. A surgical instrument for fluid injection, the surgical instrument comprising: Handheld component, configured for gripping by a user, comprising: A first lumen is disposed therein, the first lumen being configured to receive a fluid cylinder comprising one or more injectable fluids; A fluid drive system disposed within the first lumen, the fluid drive system being used to drive one or more injection fluids from the fluid cylinder into the cannula; the cannula being coupled to the handpiece and configured for insertion into the eye, the cannula comprising: A second lumen extending through it, the second lumen being for receiving the one or more injection fluids flowing out of the fluid cylinder; and A needle movably disposed within the second lumen, the needle being configured to extend from and retract into the second lumen at the distal end of the cannula.

2. The system as claimed in claim 1, wherein, The fluid drive system includes an electromechanical actuator coupled to a piston, the electromechanical actuator being configured to translate the piston within the first cavity, the piston being configured to engage with the fluid cylinder for driving the one or more injection fluids to flow out of the fluid cylinder.

3. The system as described in claim 2, wherein, The electromechanical actuator includes an electromechanical linear or rotary stepper motor.

4. The system as described in claim 3, wherein, The electromechanical actuator includes a rotary screw motor, and the piston includes a rotary lead screw, wherein rotating the rotary lead screw caused by the rotary screw motor will cause the rotary lead screw to translate linearly within the first cavity.

5. The system as claimed in claim 1, wherein, The fluid drive system includes an electro-pneumatic actuator coupled to a piston, the electro-pneumatic actuator being configured to translate the piston within the first cavity, the piston being configured to engage with the fluid cylinder for driving the one or more injection fluids to flow out of the fluid cylinder.

6. The system of claim 5, wherein, The electro-pneumatic actuator includes a pressurized fluid tank coupled to a valve, wherein adjusting the position of the valve modifies the flow rate of pressurized fluid entering the first cavity from the pressurized fluid tank, the pressurized fluid in the first cavity acting on the piston to cause the piston to translate linearly within the first cavity.

7. The system of claim 6, wherein, The valve includes at least one of the following: a solenoid valve, a proportional valve, a plug valve, a piston valve, or a knife valve.

8. The system of claim 1, wherein, The fluid drive system includes a spring actuation mechanism configured to engage with the fluid cylinder for driving the one or more injection fluids to flow out of the fluid cylinder.

9. The system of claim 8, wherein, The spring actuation mechanism includes a spring coupled to a piston, the spring providing a biasing force against the piston to cause the piston to translate linearly within the first cavity.

10. The system of claim 9, wherein, The translation of the piston within the first cavity is further controlled by a brake connected to the piston.

11. The system of claim 1, wherein, The fluid cylinder includes a premixed therapeutic solution and a non-therapeutic solution for injection.

12. The system of claim 1, wherein, The fluid cylinder includes an unmixed therapeutic solution and a non-therapeutic solution for injection, and wherein driving the one or more injection fluids from the fluid cylinder into the cannula includes mixing the therapeutic solution with the non-therapeutic solution.

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