Method and apparatus for subretinal delivery

Abstract

The subretinal injection device may include an inserter coupled to a subretinal injection needle, and a conduit having a distal end coupled to the proximal end of the injection needle and a proximal end coupled to a fluid source. The conduit may have first and second lumens, and the conduit is positioned through the inserter device. The device may further include a stabilizer for fixing the injection needle in position on the surface of the retina, and a fluid source. The fluid source may include both a first fluid reservoir containing a non-therapeutic solution and a second fluid reservoir containing a therapeutic solution. The fluid source may supply the non-therapeutic solution to the subretinal space from the first fluid reservoir through the first lumen. The fluid source may further supply the therapeutic solution to the subretinal space from the second fluid reservoir through the second lumen.

Description

Background Art

[0001] The human eye includes three main layers: an outer protective layer of an opaque white membrane known as the sclera, a thin middle layer known as the choroid, and the innermost light-sensitive layer known as the retina that lines the posterior two-thirds of the eye. The retina consists of two sub-layers, a sensory (or neural) retina containing 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 scattered light and transport oxygen, nutrients, and cellular waste products between the sensory retina and the choroid to maintain homeostasis between them. The RPE is separated from the inner sensory retina by the subretinal space.

[0002] For example, certain diseases of the eye, including age-related macular degeneration (AMD) and retinal degenerative diseases as well as genetic defects, are treatable via injection into the subretinal space. A typical procedure requires at least two people to administer a subretinal injection. For example, a lead surgeon may guide an injection device, e.g., a syringe / needle, and visually monitor the injection site, while a skilled surgical assistant squeezes the fluid from the syringe and monitors the injection volume. Thus, typically, a first syringe is prepared using a small-gauge needle and contains 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 operates 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 prepared with a small-gauge needle and contains a therapeutic fluid, e.g., a therapeutic agent. In the second step of this procedure, the second syringe is inserted through the retina into the subretinal space at approximately the same position as the first syringe. While the surgeon operates the second syringe and visually monitors the injection site, the assistant manually injects the therapeutic fluid and monitors the injection volume. As a result, there are many drawbacks to using a handheld injection device to manually control the injection in a two-step process. Some of these drawbacks are described below.

[0004] Firstly, as mentioned above, retinal tearing can occur when injections are performed using handheld injectors. In particular, retinal tearing can result from inadequate movement of the syringe / needle due to external forces from outside the eye while the needle is inserted through the retina. These external forces may include inadequate movements by the surgeon while handling the syringe or by the assistant while manually controlling the fluid injection.

[0005] Furthermore, manual control of fluid injection can have several additional drawbacks, as described above. Typically, manual control of fluid injection involves manually pressing the plunger. For example, manual control of fluid injection can result in inaccurate injection volume, which can lead to over- or under-dosing or excessive retinal stretching. In another example, manual control of fluid injection can result in high flow velocity into the subretinal space, which can damage the retina or RPE, leading to rhegmatogenous-like retinal detachment accompanied by changes in retinal morphology or RPE atrophy, for example. In yet another example, manual control of fluid injection can result in high shear force within the needle, which can be detrimental to the biological activity of various therapeutic agents delivered by the injected fluid, such as drugs, stem cells, or viral vectors.

[0006] In addition, as mentioned above, removing the first needle and inserting a second needle through the retina may have further drawbacks. For example, multiple insertions through the retina may contribute to retinal tearing. In another example, creating two different holes in the retina, one at a time with each injection step, increases the invasiveness of the procedure (e.g., retinal damage) and the possibility of fluid leakage from the subretinal space. Also, in some examples of current manual injection methods, the injected composition may remain localized in the subretinal space near the injection site and may not reach the desired tissue (e.g., the macula). [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] Each of the above problems may adversely affect the ophthalmic treatment being administered and / or result in an increased safety risk. Therefore, what is needed in the art is an improved device for ophthalmic treatment, including improved apparatus and methods for subretinal delivery. [Means for solving the problem]

[0008] Embodiments of this disclosure generally relate to devices for ophthalmic procedures, and more specifically to devices and methods for performing subretinal injections.

[0009] Specific embodiments of the present disclosure provide an apparatus for performing subretinal injection into the subretinal space of an eye, the apparatus comprising: an injection needle having a proximal and distal end, the distal end configured to be insertable into the subretinal space at a position on the surface of the retina; an inserter device detachably coupled to the injection needle; a conduit having a distal end coupled to the proximal end of the injection needle and a proximal end coupled to a fluid source, the conduit having a first lumen and a second lumen, and positioned through the inserter device; and a stabilizer configured to fix the injection needle at a position on the surface of the retina, the fluid source comprising a first fluid reservoir containing a non-therapeutic solution and a second fluid reservoir containing a therapeutic solution, the fluid source configured to deliver the non-therapeutic solution to the subretinal space from the first fluid reservoir through the first lumen, and the fluid source configured to deliver the therapeutic solution to the subretinal space from the second fluid reservoir through the second lumen.

[0010] Specific embodiments of the present disclosure provide a method for performing a subretinal injection into the subretinal space of an eye, the method comprising inserting the distal end of an injection needle into the subretinal space at a target site on the surface of the retina, the injection needle having a proximal end coupled to the distal end of a conduit, the conduit having a proximal end coupled to a fluid source, the proximal end of the injection needle being further detachably coupled to the distal end of an injector device, fixing the injection needle to the target site on the surface of the retina by applying pressure or fluid through a first lumen of the conduit to extend a stabilizer beyond the distal end of the first lumen to contact the surface of the retina, separating the injector device from the injection needle, providing a non-therapeutic solution to the subretinal space from a fluid source through a second lumen of the conduit, and providing a therapeutic solution to the subretinal space through a third lumen of the conduit using the fluid source.

[0011] To enable a more detailed understanding of the above-mentioned features of this disclosure, a more specific description of this disclosure, which is briefly summarized above, can be obtained by referring to embodiments, some of which are shown in the accompanying drawings. However, it should be noted that the accompanying drawings show only exemplary embodiments and should not be considered to limit its scope, as other equally valid embodiments may be recognized. [Brief explanation of the drawing]

[0012] [Figure 1A] A cross-sectional view of the eye according to a specific embodiment described herein is shown. [Figure 1B] A cross-sectional view of the eye according to a specific embodiment described herein is shown. [Figure 2] This image shows a cross-sectional view of an eye during a transvitreous subretinal injection procedure according to a specific embodiment of the present disclosure. [Figure 3] This image shows a cross-sectional view of an eye during a subretinal injection procedure via the suprachoroidal approach according to a specific embodiment of the present disclosure. [Figure 4] An exaggerated perspective view of an exemplary surgical system for performing a subretinal injection procedure according to a particular embodiment of the present disclosure is shown. [Figure 5]A perspective view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure is shown. [Figure 6] A perspective view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure is shown. [Figures 7A-7B] A schematic cross-sectional side view of a distal end of an exemplary infusion cannula according to a particular embodiment of the present disclosure is shown. [Figures 8A-8C] A schematic cross-sectional side view of a distal end of an exemplary infusion cannula according to a particular embodiment of the present disclosure is shown. [Figure 9A] A perspective view of an exemplary infusion needle according to a particular embodiment of the present disclosure is shown. [Figures 9B-9D] A schematic side cross-sectional view of the exemplary infusion needle of FIG. 9A according to a particular embodiment of the present disclosure is shown. [Figure 10A] A schematic side cross-sectional view of an exemplary infusion needle according to a particular embodiment of the present disclosure is shown. [Figure 10B] A schematic side view of the exemplary infusion needle of FIG. 10 in use according to a particular embodiment of the present disclosure is shown. [Figure 11A] A perspective view of an exemplary infusion needle according to a particular embodiment of the present disclosure is shown. [Figure 11B] A perspective view of an exemplary infusion needle according to a particular embodiment of the present disclosure is shown. [Figure 12] A schematic cross-sectional side view of a distal end of an exemplary infusion cannula according to a particular embodiment of the present disclosure is shown. [Figures 13A-13B] A schematic cross-sectional side view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure is shown. [Figures 14A-14B] A perspective side view of an exemplary subretinal delivery device and an infusion cannula according to a particular embodiment of the present disclosure is shown. [Figure 15A] A schematic view of an exemplary subretinal delivery system according to a particular embodiment of the present disclosure is shown. [Figure 15B] A magnified cross-sectional view of the multi-lumen conduit in FIG. 15A according to a particular embodiment of the present disclosure is shown. [Figure 15C] A top isometric view of a portion of the delivery system of FIG. 15A according to a particular embodiment of the present disclosure is shown. [Figure 15D] Schematic diagram of the delivery system of FIG. 15A in conjunction with an exemplary subretinal delivery device according to a particular embodiment of the present disclosure. [Figure 15E] Shows an enlarged side cross-sectional view of a portion of the delivery system shown in FIG. 15D according to a particular embodiment of the present disclosure. [Figure 15F] Top isometric view of a portion of a delivery system with an alternative injection needle and stabilizer according to a particular embodiment of the present disclosure. [Figures 16A-16E] It is a figure showing a cross-sectional view of an eye in different steps of performing subretinal injection using the delivery system of FIGS. 15A to 15E according to a particular embodiment of the present disclosure. [Figures 17A-17C] Shows a cross-sectional side view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure. [Figure 18A] Shows a perspective view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure. [Figure 18B] Shows a perspective view of another exemplary subretinal delivery device according to a particular embodiment of the present disclosure. [Figure 19A] Shows a perspective view of an exemplary injection cannula according to a particular embodiment of the present disclosure. [Figure 19B] Shows a perspective view of another exemplary injection cannula according to a particular embodiment of the present disclosure. [Figure 19C] Shows a cross-sectional view of an exemplary injection cannula profile according to a particular embodiment of the present disclosure. [Figure 20A] Shows a cross-sectional top view of an exemplary injection cannula according to a particular embodiment of the present disclosure. [Figures 20B-20C] Shows a cross-sectional side view of an alternative arrangement of the exemplary injection cannula of FIG. 20A according to a particular embodiment of the present disclosure. [Figures 20D-20E] Shows a cross-sectional view of an eye in different steps of performing subretinal injection using the exemplary injection cannula of FIG. 20A according to a particular embodiment of the present disclosure. [Figures 21A-21B] Shows a perspective view of an exemplary distal tip of an injection cannula according to a particular embodiment of the present disclosure. [Figure 21C]Figures 21A and 21B show a cross-sectional side view of the distal tip of an exemplary injection cannula according to a particular embodiment of the present disclosure. [Figure 22A] An exemplary distal tip perspective view of an injection cannula according to a particular embodiment of the present disclosure is shown. [Figure 22B] Figure 22A shows a cross-sectional side view of the distal tip of an exemplary injection cannula according to a particular embodiment of the present disclosure. [Figures 23A-23B] A cross-sectional side view of an exemplary internal bevel assembly for the distal tip of an injection cannula according to a particular embodiment of the present disclosure is shown. [Figures 24A-24B] A schematic perspective view of the exemplary distal tip of an injection cannula according to a particular embodiment of the present disclosure is shown. [Figure 25] A schematic perspective view of the exemplary distal tip of an injection cannula according to a particular embodiment of the present disclosure is shown. [Figures 26A-26B] An illustrative perspective view of a subretinal delivery device according to a particular embodiment of this disclosure is shown. [Figures 27A-27B] Various perspective views of exemplary subretinal delivery devices according to specific embodiments of this disclosure are shown. [Figure 28A] An exemplary cross-sectional side view of a guide cannula according to a particular embodiment of the present disclosure is shown. [Figure 28B] Figure 28A shows a cross-sectional top view of an exemplary induction cannula according to a particular embodiment of the present disclosure. [Figures 28C-28D] Figure 28A shows cross-sectional views of the eye in different steps of performing subretinal injection using the exemplary guide cannula according to a particular embodiment of the present disclosure. [Figure 29A] An exemplary perspective view of an entry cannula according to a particular embodiment of the present disclosure is shown. [Figures 29B-29C] Figure 29A shows cross-sectional views of the eye in different steps of performing subretinal injection using the exemplary entry cannula according to a particular embodiment of the present disclosure. [Figures 30A-30B] An exemplary perspective view of an entry cannula according to a particular embodiment of the present disclosure is shown. [Figure 31A-31C]A schematic cross-sectional view of an exemplary subretinal delivery device according to a particular embodiment of the present disclosure is shown. [Figures 32A-32D] A schematic side view of an exemplary support arm for supporting a delivery device during a subretinal injection procedure, according to a specific embodiment described herein, is shown. [Figure 33A] This describes an exemplary operating environment during the administration of a subretinal injection procedure according to a specific embodiment of the present disclosure. [Figure 33B] Figure 33A shows various components of the operating environment according to a specific embodiment of this disclosure. [Figures 34A-34D] The images show partial cross-sectional views of the eye in different steps of performing an exemplary subretinal injection procedure with post-injection sealing according to a particular embodiment of the present disclosure. [Modes for carrying out the invention]

[0013] For ease of understanding, the same reference numerals are used to indicate identical elements common to the drawings, where possible. It is assumed that elements and features of one embodiment can be usefully incorporated into other embodiments without further detail.

[0014] In the following description, details are provided as examples to facilitate understanding of the disclosed subject matter. However, it will be apparent to those skilled in the art that the disclosed implementations are illustrative and do not encompass all possible implementations. Therefore, please understand that references to the examples described are not intended to limit the scope of this disclosure. Any modifications and further alterations to any further use of the described devices, apparatus, methods and principles of this disclosure are fully assumed to be as normally conceivable to those skilled in the art in which this disclosure relates. In particular, it is fully assumed that features, components and / or steps described in relation to one implementation may be combined with features, components and / or steps described in relation to other implementations of this disclosure.

[0015] 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.

[0016] As used herein, the term “surgical system” may refer to any surgical system, console, or device for performing surgical procedures. For example, the term “surgical system” may 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 operating room, as is known to those skilled in the art. While specific embodiments described herein are described in relation to ophthalmic systems, tools, and environments, it should be noted that the embodiments described herein are equally applicable to other types of medical or surgical systems, tools, and environments.

[0017] Where used herein, the term "approximately" may refer to a variation of + / - 10% from the nominal value. It should be understood that such variation may be included in any value provided herein.

[0018] While generally described with reference to ophthalmic surgical devices and systems, the devices and systems described herein may be implemented in other devices and systems, such as devices and systems for other surgeries, without departing from the scope of this application.

[0019] Embodiments of this disclosure generally relate to devices and methods for ophthalmic treatment, and more specifically to devices and methods for performing subretinal injection. Subretinal injection generally refers to the delivery of fluids or other therapeutic substances or stem cells into the subretinal space between the retina and the retinal pigment epithelium (RPE) of the eye.

[0020] Cell-based therapies, in which cells such as stem cells are transplanted to or adjacent to the targeted treatment site, have been suggested to be effective for several currently untreatable conditions involving the retinal pleoplasm (RPE), including AMD and retinitis pigmentosa (AR). Cell transplantation into the human retina has the potential to restore lost vision and provide treatment for the advanced stages of retinal degeneration with significant RPE loss. Similarly, gene therapy, which involves introducing exogenous DNA (deoxyribonucleic acid) constructs into host cells to modify their activity, also holds great potential for treating retinal diseases such as AMD, AR, and choroidemia. However, to treat retinal conditions, such techniques require access to the subretinal space. Furthermore, as mentioned above, current techniques for injection into the subretinal space have many drawbacks, as the tissues surrounding the subretinal space are delicate and require a high level of skill to manipulate.

[0021] Accordingly, embodiments of the present disclosure provide improved methods and apparatus for performing subretinal injections that mitigate or even eliminate the drawbacks associated with the current technology.

[0022] Figure 1A shows a cross-sectional view of eye 100. Several features of eye 100 are described herein. Eye 100 includes a sclera 102 attached to the retinal membrane or retina 104 by the choroid (not shown in Figure 1A). The choroid contains connective tissue that attaches the retina 104 to the inner wall of the posterior sclera 102 of eye 100 and provides oxygen and nutrients to the outer layer of the retina 104. The cornea 108 allows light to enter eye 100, and the light is focused onto the retina 104 through the vitreous cavity 112 by the lens 110, and the retina contains photoactivated cells that transmit signals to the brain via the optic nerve 106.

[0023] Problems can arise in the eye that impair the proper development and / or function of the retina as it provides signals to the brain for processing into a recognizable image. Potential treatments or therapies for such eye problems may include delivering genetic material and / or stem cells to a desired area of ​​the subretinal space where the immune response can be sufficiently suppressed, to the area just above the choroid between the outermost layer of the retina and the retinal pigment epithelium (RPE).

[0024] The region of interest 114 is shown below the eye 100 in Figure 1A. Details of the region of interest 114 are shown in Figure 1B.

[0025] Referring here to Figure 1B, the region of interest 114 of eye 100 is shown enlarged to provide more detail of the layers of the retina 104. Note that the layers are not drawn to scale. As shown in Figure 1A, the retina 104 comprises several layers, including the primary retinal layer 122, the subretinal space 124, and the opaque layer 126. The retinal layer 122 includes an internal limiting membrane in contact with the vitreous fluid filling the vitreous cavity 112. The retinal layer 122 further includes a nerve fiber sublayer, a ganglion cell sublayer, an internal plexiform sublayer, an internal granular sublayer, an external plexiform sublayer, and an external granular sublayer. The 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.

[0026] Once the therapeutic agent is delivered to the retina 104, the fluid containing the therapeutic agent is delivered into the space between the retinal layer 122 and the retinal pigment epithelium of the opaque layer 126, i.e., into the subretinal space 124. Conventionally, a thin needle is used to puncture the retinal layer 122 and introduce the fluid containing the therapeutic agent into this subretinal space. In some examples, a bleb may then be formed, for example, by injecting a balanced salt solution (BSS), and the fluid containing the therapeutic agent is then injected into the space formed by the bleb. Bleb formation can provide a space for injecting the therapeutic agent without exposing the therapeutic agent to the fluid pressure required to form the space. In some examples, a single injection can be used to form a bleb and introduce the therapeutic agent. The fluid containing the therapeutic agent is introduced into the subretinal space 124 between the photoreceptor sublayer and the retinal pigment epithelium, where the immune system response to the therapeutic agent may be relatively suppressed.

[0027] During the subretinal delivery process, care must be taken to avoid retinal rupture caused by the formation of blebs with high retinal tension or undesirable movement of the injection needle, puncture of the retinal pigment epithelium of the opaque layer 126 by the injection needle, damage to the retinal pigment epithelium caused by excessive injection flow rate resulting in rhegmatogenous-like retinal detachment with changes in retinal morphology, and backflow or perfusion (e.g., outflow) of the therapeutic agent into the vitreous cavity 112 through puncture of the retinal layer 122. These are all problems associated with current subretinal injection devices and methods. Accordingly, the systems, apparatus and methods of the present disclosure, whose embodiments are described herein, enable the performance of subretinal injection while avoiding the above situations by providing efficient access to the subretinal space and proper positioning of the delivery device needle tip in the retina 104, stabilizing the delivery device needle and / or delivery device handpiece to reduce the effects of undesirable movement by the user, and facilitating improved fluid control / handling of the injected fluid by reducing leakage into the vitreous cavity 112.

[0028] Generally, there are two main methods for administering subretinal injections: (1) the suprachoroidal method shown in Figure 2, and (2) the suprachoroidal method shown in Figure 3. Embodiments of this disclosure may be used in combination with one or both of these methods, as will be described in more detail below.

[0029] As shown in the cross-sectional view of the eye 200 in Figure 2, in the transvitreal method, the injection cannula 240 of the delivery device can be inserted through a valved insertion cannula 230 (or other entry cannula) positioned through an incision in the sclera 202 of the eye 200 (i.e., a scleral incision) and guided through the vitreous cavity 212 toward the retina 204. In certain 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 having a hub at its proximal end is inserted into the eye 200 until the bottom surface of the hub contacts the sclera 202 (thus forming an incision). The trocar is then removed from the eye 200, as shown in Figure 2, leaving the valved insertion cannula 230 in place. In certain embodiments, the valved insertion cannula 230 of the delivery device, and therefore the injection cannula 240, can be inserted into the eye 200 through the cornea 208, rather than through the sclera (e.g., transscleral), and the injection cannula 240 enters the vitreous cavity 212 (e.g., transcorneal) by bypassing the lens 210.

[0030] The injection cannula 240 of the delivery device is guided through the vitreous cavity 212 until its distal end 242 is adjacent to the retina 204 and positioned near the target injection site in the subretinal space 224. At this point, the injection needle of the delivery device, which may be positioned within the injection cannula 240 and configured to extend slidably from the distal end 242, can be inserted through the retina 204 into the subretinal space 224, for example, between the outermost neural layer and the retinal pigment epithelium of the retina 204, for injection.

[0031] As shown in the cross-sectional view of the eye 300 in Figure 3, in the suprachoroidal approach, the flexible injection cannula 340 of the delivery device can be inserted through an incision in the sclera 302 of the eye 300 and guided to the target injection site through the suprachoroidal space (SCS) 332 without passing through the vitreous cavity 312. In certain embodiments, a valved cannula similar to the entry cannula 230 or other entry cannula may be used to facilitate the entry of the injection cannula 340 into the eye 300 through the sclera 302. The suprachoroidal space 332 is a potential space between the sclera 302 and the choroid 316 of the eye 300, traversing around the posterior segment of the eye 300. When the distal end 342 of a flexible injection cannula 340 in the suprachoroidal space 332 is positioned adjacent to the target injection site in the subretinal space 324, an injection needle 344 of a delivery device, which may be located within the injection cannula 340 and configured to extend slidably from the distal end 342, is inserted into the subretinal space 324 through the choroid 316 for injection, compared to being inserted through the retina 304 in the suprachoroidal method. In certain embodiments, the injection cannula 340 includes a microcannula, and the injection needle 344 includes a microneedle.

[0032] Figure 4 shows a perspective view of an exemplary surgical system 400 that may be used with embodiments of the present disclosure for performing subretinal injection procedures. In certain examples, the surgical system 400 may include, but is not limited to, surgical systems for ophthalmic procedures such as retinal procedures and treatments, as sold by Alcon in 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 relating to system operation and / or system performance during a surgical procedure, which may be located, for example, within a graphical user interface (GUI).

[0033] Generally, the console 402 includes one or more systems or subsystems that enable a surgeon to perform various surgical procedures, such as retinal procedures. For example, subsystems may be used together to perform a vitrectomy surgical procedure before injecting therapeutic agents to provide improved access to the retina. In certain embodiments, the subsystem includes a control system having one or more foot pedal subsystem 408, which includes a foot pedal 410 having several foot-operated controls, and a device control system or subsystem 412 that communicates with a handheld surgical instrument, indicated as a delivery device 414. Another subsystem may be used to provide tracking of the distal end of the delivery device 414. This may be done using optical coherence tomography (OCT), using a displacement sensor, or by other suitable mechanism. Tracking information and other information may be provided on a display 406 or a surgical microscope head-up display. Some embodiments of the console 402 may further include a vitrectomy cutter subsystem having a vitrectomy handpiece, and a pump / vacuum, which may also be controlled using the foot pedal 410 and / or the device control subsystem 412. These subsystems of console 402 may overlap and cooperate to perform various aspects of a procedure, and may operate separately and / or independently of one or more procedures. That is, some procedures may utilize one or more subsystems, while others do not.

[0034] Referring here to Figure 5, an exemplary subretinal delivery device 500 according to a particular embodiment of the present disclosure is shown in a perspective view. The delivery device 500 may be used as the delivery device 414 of the surgical system 400 of Figure 4, and its embodiments may be combined with other delivery devices and / or components described herein, without limitation.

[0035] The delivery device 500 includes a handle 502 and an injection cannula 510 having a proximal end 516 coupled to the distal end 504 of the handle 502 and extending distally therefrom. The injection cannula 510, which may include a tube, is generally formed from any suitable surgical-grade material, such as a metal or a thermoplastic polymer material. Examples of metallic materials include aluminum, stainless steel, and other metal alloys. Examples of suitable thermoplastic polymer materials include polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0036] As further shown in Figure 5, a curved or substantially straight injection needle 512 is positioned within the injection cannula 510 to puncture the desired ocular tissue (e.g., the retina or choroid) and deliver fluid into the subretinal space. In exemplary embodiments, 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, injection cannulas and injection needles of other sizes / gauges may be used.

[0037] In certain embodiments, the injection needle 512 is configured to slidably extend from the distal tip 511 at the distal end 514 of the injection cannula 510 and retract into it, which facilitates the prevention of damage to the injection needle 512 during insertion and / or movement of the injection cannula 510 within the eye. Such operation of the injection needle 512 can be controlled by any suitable mechanism. In the example of Figure 5, the operation of the injection needle 512 is controlled by a toggle 540 on a handle 502 which may be directly or indirectly coupled to the injection needle 512. In certain embodiments, the toggle 540 includes a sliding button or switch, wherein sliding the toggle 540 distally 542 by the user (e.g., a surgeon) extends the injection needle 512 from the injection cannula 510, and sliding the toggle 540 proximal 544 retracts the injection needle 512 into the injection cannula 510.

[0038] In certain embodiments, the sliding toggle 540 may also be lockable, thereby allowing the injection needle 512 to be fixed in either the extended or retracted position. Locking the injection needle 512 prevents unintended movement of the injection needle 512 during retinal procedures, such as subretinal injections, thereby reducing the risk of undesirable tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 540 for adjustment, the toggle 540 may be continuously pushed down by the user, allowing the user to freely slide the toggle 540 and thus freely extend or retract the injection needle 512. In this example, the toggle 540 may only be movable while being pushed down by the user (e.g., activated). Correspondingly, when the toggle 540 is released, the toggle 540 rises and locks in place, thereby locking the injection needle 512 in place. Such a push-button locking mechanism may be facilitated in part by one or more tracks, including grooves or notches, along which a spring lever and a toggle 540 can slide, arranged together with the handle 502.

[0039] As further shown in Figure 5, in certain embodiments, a flexible fluid conduit 520 for supplying an infusion fluid, e.g., non-therapeutic and / or therapeutic solution, to the delivery device 500 is located through the proximal end 506 of the handle 502 and may be fluid-coupled to an infusion needle 512 within the handle 502. In certain 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 in this specification). Generally, the fluid conduit 520 includes a supply line in which an infusion fluid (e.g., non-therapeutic and / or therapeutic solution) from a fluid source (not shown in Figure 5) can be supplied to the delivery device 500 for delivery to the eye. In certain embodiments, the fluid conduit 520 includes a multi-lumen conduit providing multiple parallel flow paths from a separate fluid reservoir of the fluid source to the infusion needle 512 so that multiple fluid types of infusions can be performed using only one needle. In certain embodiments, the fluid source includes a fluid system which may be coupled to the fluid conduit 520 via a connection 522 such as a Luer lock or other male-female coupling. In certain other embodiments, the handle 502 may be fluid-coupled to the injection cannula 510 and include an operable internal chamber containing the injection fluid. In such embodiments, the subretinal delivery device 500 does not need to be coupled to any external fluid conduit.

[0040] In further embodiments, to simplify fluid preparation for subretinal injection, the injection fluid may be supplied to the delivery device 500 from a pre-filled cartridge that can be coupled to the fluid drive system of the delivery device 500 or to an external fluid system connected to the delivery device 500 via a fluid conduit 520. In certain embodiments, the pre-filled cartridge includes a single lumen containing a pre-mixed therapeutic substance. In other embodiments, the pre-filled cartridge includes two or more lumens containing unmixed therapeutic substances that can be automatically or semi-automatically mixed, for example, within the fluid system or delivery device, before performing subretinal injection. Cartridges for therapeutic agents are described in further detail below.

[0041] Referring here to Figure 6, another exemplary subretinal delivery device 600 according to a particular embodiment of the present disclosure is shown in perspective. The delivery device 600 is substantially similar to the delivery device 500 and may also be used as the delivery device 414 of the surgical system 400 in Figure 4. The embodiments of the delivery device 600 may be combined with other delivery devices and / or components described herein, but are not limited. However, unlike the delivery device 500, the handle of the delivery device 600 is "rotatable" as described below.

[0042] As shown in Figure 6, the delivery device 600 includes a handle 602, a tubular infusion cannula 610 coupled to the distal end 604 of the handle 602 and having a proximal end 616 extending therefrom, and a curved or substantially straight infusion needle 612 (a curved infusion needle 612 is shown) positioned within the infusion cannula 610. In certain embodiments, a flexible fluid conduit 620 for supplying an infusion fluid (e.g., a non-therapeutic solution and / or therapeutic solution) to the delivery device 600 may be positioned through the proximal end 606 of the handle 602 and fluid-coupled to the infusion 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 certain embodiments, the fluid conduit 620 includes a multi-lumen conduit. Similar to the fluid conduit 520, the fluid conduit 620 includes a connector 622 located at its proximal end for coupling to a fluid source, such as a fluid system integrated with a surgical console.

[0043] The injection needle 612 is configured to slidably extend from the distal tip 611 at the distal end 614 of the injection cannula 610, retract into it, and prevent damage to the injection needle 612. In Figure 6, the operation of the injection needle 612 is controlled by an external toggle 640, which can completely enclose or wrap around the handle 602 near the distal end 604 (for example, around the longitudinal axis X of the handle 602) and can be directly or indirectly coupled to the injection needle 612 within the handle 602. Similar to the toggle 540 described above, sliding the toggle 640 distally 642 causes the injection needle 612 to extend from the injection cannula 610, and sliding the toggle 640 proximal 644 causes the injection needle 612 to retract into the injection cannula 610. Because the external toggle 640 wraps around the entire handle 602, the user (e.g., a surgeon) can control the extension and retraction of the injection needle 612 while the delivery device 600 is positioned in the user's hand at any given rotational angle. Thus, the handle 602 of the delivery device 600 can be described as "rotatable." This rotatability is particularly beneficial with a curved injection needle 612. For example, when using such a curved injection needle 612, it may be beneficial for the user to rotate the handle 602, and therefore the injection needle 612 coupled thereto, to one side or the other for precise fluid delivery to the target injection site. Thus, the external toggle 640 facilitates the control of the extension / retraction of the injection needle 612 independently of the rotation of the handle in these examples.

[0044] In certain embodiments, instead of a continuous toggle around the handle 602, the external toggle 640 includes a plurality of buttons (e.g., three, four, or more buttons) distributed symmetrically or asymmetrically around the handle 602. In certain embodiments, the external toggle 640 is lockable so that the injection needle 612 can be fixed in the extended or retracted position.

[0045] Figures 7A and 7B show schematic cross-sectional side views of the distal end 714 of an exemplary injection cannula 710 according to a particular embodiment of the present disclosure. The injection cannula 710 is an exemplary tubular injection cannula that can be used with the delivery devices 500 and 600 of Figures 5 and 6, or other delivery devices for subretinal injection described herein. The embodiments of the injection cannula 710 may be combined with other delivery devices and / or components described herein, but are not limited.

[0046] As shown, the injection needle 712 is positioned within the injection cannula 710 and configured to slidably extend from its distal end 714 and retract into it. 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 can provide a fluid connection between the injection needle 712 and a flexible fluid conduit for supplying the injection fluid to the injection needle 712. In such embodiments, 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 certain embodiments, such a fluid conduit includes a multi-lumen conduit that provides multiple parallel flow paths from a separate fluid reservoir of a fluid source to the injection needle 712, so that injection may be performed using only one needle.

[0047] An annular insert 730 is also positioned within the infusion cannula 710 at its distal end 714 and around the infusion needle 712. The annular insert 730 surrounds the infusion needle 712 and acts as a mechanical reinforcement or stabilizer for the infusion needle 712 by preventing or reducing its lateral movement during use. In certain embodiments, the stiffness of the infusion needle 712 can be adjusted or controlled by extending or retracting the infusion needle 712 through the annular insert 730 to / from the infusion cannula 710. For example, to increase the flexibility of the infusion needle 712 and decrease its stiffness, the infusion needle 712 may be extended from the infusion cannula 710 through the annular insert 730, as shown in Figure 7A. Exposing a larger portion of the infusion needle 712 from the infusion cannula 710 (e.g., forming a longer "freely hanging" needle) allows the needle to be more flexible. Conversely, to increase the rigidity of the injection needle 712 for puncturing tissue, the injection needle 712 may be retracted toward / into the injection cannula through the annular insert 730, as shown in Figure 7B. Reducing the length of the injection needle 712 exposed from the injection cannula 710 (e.g., forming a shorter "freely hanging" needle) reduces the flexibility of the needle.

[0048] Therefore, the adjustable stiffness of the injection needle 712 allows a user, such as a surgeon, to adjust it to a higher stiffness for easier puncture during subretinal injection. Higher stiffness reduces the amount of pressure required to puncture the retina (or other ocular tissue / membrane), further reducing the risk or occurrence of tissue damage, such as that caused by the traction of the injection needle 712 on the tissue during puncture. At the same time, the adjustable stiffness of the injection needle 712 allows the user to adjust it to a lower stiffness (or higher flexibility) after puncturing the desired tissue or membrane (e.g., the retina) to reduce the risk of tissue damage caused by unintended movements or tremors by the user. The extension and retraction of the injection needle 712 for adjusting the needle's stiffness can be controlled by any suitable mechanism, including those shown in Figures 5 and 6.

[0049] The annular insert 730 is generally formed from any suitable surgical-grade material, such as a metal or thermoplastic polymer material, which facilitates the extension and retraction of the injection needle 712 to and from the injection cannula 710. Examples of metallic materials include aluminum, stainless steel, and other metallic alloys. Examples of suitable thermoplastic polymer materials include polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0050] As shown in Figures 7A and 7B, the annular insert 730 can be fixedly coupled to the inner wall 708 of the injection cannula 710, and thus the inner diameter 710 of the injection cannula 710 ID Outer diameter 730 which is virtually identical OD It may have the following. In certain embodiments, the distal surface 732 of the annular insert 730 is coplanar with the distal surface 740 of the injection cannula 710. The annular insert 730 has an inner diameter 730 that substantially matches the outer diameter of the injection needle 712, in order to facilitate the extension and retraction of the injection needle 712 to and from the injection cannula 710, while also reducing the gap between the injection needle 712 and the injection cannula 710. ID It may have an inner diameter of 730. ID This may be equal to or approximately equal to the outer diameter of a 38 gauge needle.

[0051] Figures 8A–8C show schematic cross-sectional side views of another distal end 814 of an exemplary injection cannula 810 according to a particular embodiment of the present disclosure. The injection cannula 810 is an exemplary injection cannula that may be used with the delivery devices 500 and 600 of Figures 5 and 6 or other delivery devices for subretinal injection as described herein. Embodiments of the injection cannula 810 may be combined with other delivery devices and / or components described herein, but are not limited.

[0052] As shown, the injection needle 812 is positioned within the tubular injection cannula 810 and is configured to slidably extend from its distal end 814 and retract into it. Similar to the embodiments of Figures 7A and 7B, the proximal end 806 of the injection needle 812 is coupled to an inner fluid shaft 820 for fluid coupling between the injection needle 812 and a flexible fluid conduit connected to a fluid source. In such embodiments, the inner fluid shaft 820 may be slidably positioned within the cannula 810 to facilitate extension and retraction of the injection needle 812. However, in certain embodiments, the injection needle 812 may be directly coupled to the fluid conduit.

[0053] In Figures 8A to 8C, the injection needle 812 includes a pre-formed, curved needle made of an elastic (or flexible) material. In certain embodiments, the injection needle 812 may be made of a superelastic material such as nitinol. The use of a curved elastic material allows for an adjustable insertion angle of the injection needle 812 during the procedure of subretinal injection, thereby facilitating easier positioning into the subretinal space and easier access to peripheral areas of the retina that are normally inaccessible due to the need for linear injection. In some examples, the adjustable insertion angle of the injection needle 812 facilitates a reduction in damage to tissues beneath the subretinal space, such as the retinal pigment epithelium (RPE), because the subretinal space can be entered at a lower angle, thereby improving the safety of subretinal injection.

[0054] In certain 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 / to the injection cannula 810. In certain embodiments, the curvature of the injection needle 812 can be increased by extending the injection needle 812 from the injection cannula 810, as shown in Figures 8A to 8C. In the embodiments of Figures 8A to 8C, the injection cannula 810 does not need to include an annular insert at its distal end 814 in order to facilitate the bending or curvature of the injection needle 812 when extending from the injection cannula 810. However, in certain embodiments, an annular insert similar to the annular insert 730 can be used.

[0055] Referring to Figure 8A, in the retracted state, the injection needle 812 can be substantially straight or slightly curved, as its curvature is limited by the inner diameter of the injection cannula 810. In Figure 8B, the injection needle 812 is partially extended from the injection cannula 810, and its curvature begins to increase as it exits the injection cannula 810. In Figure 8C, the injection needle 812 is fully extended from the injection cannula 810 and is positioned at its maximum curvature as its elastic material deforms back to its original shape. Thus, in the illustrated example, it can be inferred that the greater the distance the injection needle 812 extends from the injection cannula 810, the greater the angle of curvature C of the injection needle 812. In certain embodiments, the maximum angle of curvature C of the injection needle 812 is 90° with respect to the main longitudinal axis of the injection cannula 810.

[0056] Figures 9A to 9D show various illustrations of an exemplary injection needle 912 according to a particular embodiment of the present disclosure. The injection needle 912 is an exemplary injection needle that may be used with any of the injection cannulas and / or delivery devices for subretinal injection as described herein. Thus, embodiments of the injection needle 912 may be combined with other delivery devices and / or components described herein, without limitation. For illustrative purposes, the injection needle 912 is shown positioned within a tubular injection cannula 910.

[0057] As shown, the injection needle 912 includes a stepped needle. In other words, the injection needle 912 includes two or more parts having different outer diameters, the outer diameters gradually increasing in a stepwise (i.e., incremental) manner along the length of the injection needle 912 in the proximal direction. In certain embodiments, as shown in Figures 9A to 9D, the injection needle 912 has a first outer diameter 920 OD A first distal portion 920 having a second outer diameter 930 OD It includes a second proximal portion 930 having a 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 920 is 920. ODLarger than or equal to 38. For example, the distal portion 920 may have a gauge of 38, and the proximal portion 930 may have a gauge of 37, 36, 35, 34, 33, 32, 31, 30 or greater. In another example, the distal portion 920 may have a gauge of 41, and the proximal portion 930 may have a gauge of 40, 39, 38, 37, 36, 35, 34, 33 or greater. In yet another example, the distal portion 920 may have a gauge of 41, and the proximal portion 930 may have a gauge of 38 or greater.

[0058] The stepped outer morphology of the injection needle 912 facilitates improved safety during subretinal injection by ensuring that the injection needle 912 does not pass through the subretinal space and enter the underlying tissue, thereby damaging such tissue. For example, when performing subretinal injection using a transvitreous method as shown in Figure 9B, the proximal portion 930 can act as a mechanical stopper, preventing the distal portion 920 of the injection needle 912 from passing through the subretinal space 928 and puncturing the RPE 926. Thus, 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. In addition, the stepped outer morphology of the injection needle 912 (e.g., a wider proximal portion 930) can prevent the fluid injected into the subretinal space 928 from leaking or flowing out of the subretinal space 928 through the puncture wound formed by the injection needle 912.

[0059] In certain embodiments, in addition to having a stepped outer morphology, the injection needle 912 may have a stepped inner morphology. For example, as shown in Figure 9C, the injection needle 912 may include a first smaller inner diameter 940 substantially corresponding to the distal portion 920 and a second larger inner diameter 950 substantially corresponding to the proximal portion 930. The transition from the larger inner diameter 950 to the smaller inner diameter 940 results in a reduction in fluid resistance, thereby reducing the overall force of the fluid jet flow distributed by the injection needle 912. Therefore, the use of stepped inner diameters can reduce the risk or occurrence of damage to the tissue surrounding the subretinal space (e.g., RPE) during fluid injection. However, in certain other embodiments, the injection needle 912 may include a single inner diameter 960 throughout the length of the injection needle 912, as shown in Figure 9D.

[0060] In certain embodiments, the stepped shape of the injection needle 912 is formed by shrinking or pressing the distal portion 920 to a desired shape / dimension. In certain embodiments, the stepped shape of the injection needle 912 is formed by expanding the proximal portion 930 to a desired shape / dimension. In certain embodiments, the stepped shape of the injection needle 912 is formed by assembling two separate tubes together by any suitable technique, including welding or the use of adhesive.

[0061] Figures 10A and 10B show various diagrams of another injection needle 1012 according to a particular embodiment of the present disclosure. The injection needle 1012 is an exemplary injection needle that may be used with any of the injection cannulas and / or delivery devices described herein. Thus, embodiments of the injection needle 1012 may be combined with other delivery devices and / or components described herein without limitation. For illustrative purposes, the injection needle 1012 is shown positioned within a tubular injection cannula 1010 and coupled at its proximal end 1006 to an inner fluid shaft 1020 within the injection cannula 1010.

[0062] As shown in Figure 10A, the injection needle 1012 includes a sealing element 1030 positioned around a portion of its distal end 1004. In certain embodiments, the sealing element 1030 includes an annular ring formed around the injection needle 1012 (surrounding the injection needle 1012). However, other forms are also conceivable. Generally, in embodiments where the injection needle 1012 is configured to extend from / retract into the injection cannula 1010, 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, so that the sealing element 1030 can be fitted into the injection cannula 1010. In certain embodiments, the sealing element 1030 is formed from a flexible, elastic, or pliable material having sealing properties that prevent damage to the tissue it comes into contact with. For example, the sealing element 1030 may include a silicone or rubber-based material.

[0063] In certain embodiments, the segment 1040 of the injection needle 1012 distal to the sealing element 1030 may have a length L corresponding to the thickness of the retina along the main longitudinal axis A of the injection needle 1012 (labeled 1024 in Figure 10B). This length L, combined with the increased outer dimension of the sealing element 1030 relative to the injection needle 1012, ensures that during injection, the injection needle 1012 does not pass through the subretinal space (labeled 1028 in Figure 10B) and does not enter underlying tissues such as the RPE (labeled 1026 in Figure 10B). Thus, in such examples, the sealing element 1030 functions as a mechanical stopper similar to the proximal portion of the stepped injection needle in Figures 9A-9C, reducing the risk of damage to tissues beneath the subretinal space 1028.

[0064] In certain embodiments, the sealing element 1030 can prevent the fluid injected into the subretinal space 1028 from leaking or flowing out of the subretinal space 1028 through the puncture wound formed by the injection needle 1012. For example, as shown in Figure 10B, the sealing element 1030 can prevent the injected fluid from escaping through the retina 1024.

[0065] Figures 11A and 11B show various diagrams of another injection needle 1112 according to a particular embodiment of the present disclosure. The injection needle 1112 is an exemplary injection needle that can be used with any of the injection cannulas and / or delivery devices for subretinal injection as described herein. Thus, embodiments of the injection needle 1112 can be combined with other delivery devices and / or components described herein, without limitation.

[0066] As shown in Figure 11A, the injection needle 1112 includes a beveled tip 1130 having a port 1134 at its distal end 1104. At least a portion of the end face 1132 of the beveled tip 1130 is beveled or angled at an angle not perpendicular to the main longitudinal axis A of the injection needle 1112. That is, part or all of the end face 1132 is non-planar with respect to a plane perpendicular to the main axis A of the injection needle 1112. In certain embodiments, part or all of the end face 1132 of the injection needle 1112 is set at an angle of about 0° to about 90° with respect to a plane perpendicular to the main axis A, for example, about 30° to about 60° with respect to such a plane. In certain 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 on tissues such as the retina and easier puncture in order to reach the subretinal space during the performance of subretinal injection. Therefore, the inclined tip 1130 facilitates a reduction in ocular tissue rupture during injection, thereby improving the safety of such procedures compared to the use of other tip configurations.

[0067] In certain embodiments, the injection needle 1112 further includes a lateral port 1136 located through the side wall 1138 of the injection needle 1112. While the port 1134 through the inclined tip 1130 serves as the primary outlet for the outflow of the injected fluid, the lateral port 1136 may serve as a secondary outlet for such injected fluid. Thus, the inclusion of the lateral port 1136 facilitates the reduction of the fluid jet flow of the injected fluid through / from the port 1134 during injection, which may be positioned adjacent to and / or facing one or more tissues during injection. For example, during transvitreous subretinal injection, the port 1134 may be positioned adjacent to and facing the RPE in the subretinal space. Thus, during injection, the injected fluid is directed towards the RPE, which can cause damage to the RPE if injected with excessive force. By including the lateral port 1136, a portion of the injected fluid is directed / flowed peripherally, thereby reducing the fluid jet flow directed towards the RPE and minimizing the damage caused thereby.

[0068] In a further embodiment, the injection needle 1112 may not include a port 1134 through the inclined tip 1130, and instead may include only a side port 1136 as an outlet for the injected fluid. In such an embodiment, the injection needle 1112 may be referred to as a “closed” needle because the inclined tip 1130 may have a solid closed end face 1132.

[0069] Figure 12 shows a schematic cross-sectional side view of the distal end 1214 of an exemplary injection cannula 1210 according to a particular embodiment of the present disclosure. The injection cannula 1210 is an exemplary tubular injection cannula that can be used with any of the delivery devices for subretinal injection as described herein. Thus, embodiments of the injection cannula 1210 may be combined with other delivery devices and / or components described herein, but are not limited.

[0070] As shown, the injection needle 1212 is positioned within the injection cannula 1210 and coupled to an internal fluid shaft 1220 that extends along the length of the internal channel 1221 of the injection cannula 1210. The internal channel 1221 of the injection cannula 1210 extends from the proximal end to the distal end 1214 of the injection cannula 1210. The injection needle 1212 and the internal fluid shaft 1220 are configured to slidably extend from the distal end 1214 and retract into it, for example, when a toggle operably coupled to the internal fluid shaft 1220 is activated. However, in other embodiments, the injection needle 1212 may be directly and slidably coupled to the injection cannula 1210 without the internal fluid shaft 1220. In such embodiments, the injection needle 1212 may extend along the entire length of the internal channel 1221.

[0071] Similar to the injection cannula 1210, the internal fluid shaft 1220 and the injection needle 1212 each contain their own internal channels 1222 and 1223, respectively. In the example in Figure 12, internal channel 1222 extends from the proximal end of the internal fluid shaft 1220 to its distal end 1244, and internal channel 1223 extends from the proximal end 1224 to its distal end 1226 of the injection needle 1212. During subretinal injection, the injection fluid (e.g., non-therapeutic solution and / or therapeutic solution) from a fluid source in fluid communication with the injection needle 1212 flows through internal channels 1221, 1222 and / or 1223 and is dispensed from the distal end 1226 of the injection needle 1212.

[0072] 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 inner fluid shaft 1220, and the injection needle 1212, respectively. In the embodiment shown in Figure 12, the inner walls 1232 and 1234 have coatings 1240 or 1242 placed thereon, respectively. The coatings 1240 and 1242 are configured to reduce surface adhesion and other influences on the surfaces of the inner walls 1232 and 1234 to the injection fluid flowing through the inner fluid shaft 1220 and the injection needle 1212. Thus, the coatings 1240 and 1242 facilitate lower fluid resistance through the inner fluid shaft 1220 and the injection needle 1212, thereby allowing for lower pressure to be applied to generate the fluid flow required for subretinal injection.

[0073] In certain embodiments, coatings 1240 and / or 1242 include polymer brush coatings such as polymer brush coatings formed from poly(ethylene oxide) (PEO), poly(methyl methacrylate) (PMMA), poly(hydroxyethyl methacrylate) (PHEMA), combinations thereof, and equivalents thereof. In certain embodiments, coatings 1240 and / or 1242 include fluoropolymer coatings such as coatings formed from polytetrafluoroethylene (PTFE), ethylenetetrafluoroethylene (ETFE), perfluoroalkoxy (PFA), chlorotrifluoroethylene (E-CTFE), combinations thereof, and the like. In certain embodiments, coatings 1240 and / or 1242 include polyetheretherketone (PEEK) coatings. Other functionalized coatings are also conceivable. Generally, coatings 1240 and / or 1242 have a thickness of about 1 nm (nanometer) to about 1000 nm, for example, about 1 nm to about 500 nm, for example, about 1 nm to about 100 nm. In certain embodiments, coatings 1240 and 1242 are substantially identical. For example, coatings 1240 and 1242 may include the same type, material, thickness, etc. In certain other embodiments, coatings 1240 and 1242 are different. For example, coatings 1240 and 1242 may include different types, materials, thickness, etc.

[0074] It should be noted that if the injection needle 1212 is directly coupled to the injection cannula 1210 without the internal fluid shaft 1220, the coating 1240 may be positioned along the inner wall 1230 of the injection cannula 1210.

[0075] Referring here to Figures 13A and 13B, another exemplary subretinal delivery device 1300 is shown in a schematic side section view according to a particular embodiment of the present disclosure. The delivery device 1300 may be used in combination with, but not limited to, an injection cannula, an injection needle, or any other component described herein, for example, as the delivery device 414 of the surgical system 400 in Figure 4.

[0076] The delivery device 1300 includes a handle 1302, a tubular infusion cannula 1310 having a proximal end 1316 coupled to the distal end 1304 of the handle 1302 and extending distally therefrom, and a curved or substantially straight infusion needle 1312 positioned within the infusion cannula 1310 (a straight infusion needle 1312 is shown) and configured to slidably extend from the infusion cannula 1310 and retract into it upon operation of a toggle 1362. In certain embodiments, the infusion needle 1312 is coupled to an internal fluid shaft at least partially positioned within the cannula 1310 for fluid coupling between the infusion needle 1312 and the toggle 1362 or fluid conduit. In such embodiments, the internal fluid shaft may be slidably positioned within the cannula 1310 to facilitate extension and retraction of the infusion needle 1312 when the toggle 1362 is operated. In certain embodiments, the handle 1302 is rotatable as described above with reference to Figure 6.

[0077] The injection needle 1312 is fluid-coupled at its proximal end 1324 to the distal end 1346 of a flexible first fluid conduit 1340 located within the handle 1302, either directly or indirectly. In certain embodiments, the first fluid conduit 1340 is made from silicone, thermoplastic polyurethane (TPU), a combination thereof, or other flexible material. The proximal end 1344 of the first fluid conduit 1340 terminates at or substantially near the proximal end 1306 of the handle 1302, and the first fluid conduit 1340 is fluid-coupled directly or indirectly to the distal end 1356 of a flexible second fluid conduit 1350, which has a proximal connector 1352 for coupling to a fluid source. Similar to the first fluid conduit 1340, in certain embodiments, the second fluid conduit 1350 is made from silicone, thermoplastic polyurethane (TPU), a combination thereof, or other flexible material. The second fluid conduit 1350 is configured as a supply line for supplying an injection fluid, such as a non-therapeutic solution and / or a therapeutic solution, from a fluid source to a delivery device 1300, more specifically, to the first fluid conduit 1340 and the injection needle 1312. In certain embodiments, the fluid source includes a fluid system which may be coupled to the second fluid conduit 1350 via a connector 1364 such as a Luer lock or other male-female coupling. During operation, the first fluid conduit 1340 facilitates the separation of the injection needle 1312 from the second fluid conduit 1350, thereby stopping any mechanical stress (e.g., tension) on the second fluid conduit 1350 at the handle 1302. This prevents such mechanical stress from acting on the injection needle 1312, otherwise the injection needle 1312 may be unintentionally withdrawn from or retracted into the injection cannula 1310.

[0078] In certain embodiments, the first fluid conduit 1340 and the second fluid conduit 1350 are of the same type, material, diameter, etc., while in certain other embodiments, the first fluid conduit 1340 and the second fluid conduit 1350 are of different types, materials, diameters, etc., for example, in certain embodiments, the first fluid conduit 1340 may contain a more flexible / contortable material compared to the second fluid conduit 1350. In certain embodiments, the first fluid conduit 1340 has a smaller or larger diameter compared to the second fluid conduit 1350.

[0079] In the embodiments shown in Figures 13A and 13B, the base 1360 of the lockable toggle 1362 fluid-couples the proximal end 1324 of the injection needle 1312 to the distal end 1346 of the first fluid conduit 1340. However, other coupling configurations and / or mechanisms between the injection needle 1312 and the first fluid conduit 1340 are conceivable. Similarly, the proximal end 1344 of the first fluid conduit 1340 is indirectly fluid-coupled to the distal end of the second fluid conduit 1350 via a connector 1364 fixedly positioned on the proximal end 1306 of the handle 1302. The connector 1364 may include any suitable type of connector, such as a male-to-male connector. Again, other coupling configurations and / or mechanisms between the first fluid conduit 1340 and the second fluid conduit 1350 are conceivable.

[0080] The toggle 1362 can be manually controlled by the user via any of the toggle mechanisms described herein to cause the operation of the injection needle 1312, for example, extension or retraction into / from the injection cannula 1310. As described above, the toggle 1362 is lockable, and therefore, when the toggle 1362 is released, the toggle 1362 is locked in place. Thus, the user can adjust the position of the injection needle 1312 by manually operating the toggle 1362, and then lock the injection needle 1312 in place by releasing the toggle 1362. However, since the injection needle 1312 is isolated 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 does not affect the position of the needle (or vice versa), and does not interrupt or unnecessarily cause repositioning of the injection needle 1312 after the user has positioned / locked the injection needle 1312 using the toggle 1352.

[0081] Figures 14A and 14B show an exemplary subretinal delivery device 1400 having an articulated and tubular injection cannula 1410 according to a particular embodiment of the present disclosure. The delivery device 1400 with the injection cannula 1410 may be used, for example, as the delivery device 414 of the surgical system 400 in Figure 4 or as other surgical systems for subretinal injection described herein. The embodiments of the delivery device 1400 may be combined with other delivery devices and / or components described herein, but are not limited.

[0082] As shown in Figure 14A, the delivery device 1400 further includes a handle 1402, and the proximal end 1416 of the infusion cannula 1410 is coupled to the distal end 1404 of the handle 1402, extending distally therefrom. Inside the infusion cannula 1410 is a curved or substantially straight infusion needle 1412 (a straight infusion needle 1412 is shown) configured to slidably extend from the infusion cannula 1410 and retract inward upon operation of a toggle 1440. In certain embodiments, the infusion needle 1412 is coupled to an internal fluid shaft at least partially located inside the cannula 1410 for fluid coupling between the infusion needle 1412 and the toggle 1440 or fluid conduit. In such embodiments, the internal fluid shaft may be slidably located inside the cannula 1410 to facilitate extension and retraction of the infusion needle 1412 when the toggle 1440 is operated. In certain embodiments, the handle 1402 is rotatable as described above with reference to Figure 6.

[0083] In certain embodiments, a flexible fluid conduit 1420 for supplying an injection fluid (e.g., a non-therapeutic solution and / or therapeutic solution) to the delivery device 1400 may be located through the proximal end 1406 of the handle 1402 and fluid-coupled to an 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 certain embodiments, the fluid conduit 1420 includes a multi-lumen conduit providing multiple parallel flow paths from a separate fluid reservoir of the fluid source to the injection needle 1412, so that injection may be performed using only one needle.

[0084] The injection cannula 1410 and / or injection needle, which may include a tube, is generally formed from any suitable surgical-grade material, such as metal or thermoplastic polymer material. Examples of metallic materials include aluminum, stainless steel, and other metal alloys. Examples of suitable thermoplastic polymer materials include polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0085] In the examples of Figures 14A and 14B, the infusion cannula 1410 is controllably articulated. In other words, the infusion cannula 1410 can be controllably bent by manual adjustment by the user. To enhance the articulated properties of the infusion cannula 1410, the infusion cannula 1410 may include a number of features 1460 formed on its outer surface 1462, which allow for flexibility of the infusion cannula 1410 in one or more directions perpendicular to the main longitudinal axis A of the infusion cannula 1410. For example, in certain embodiments, the features 1460 may be formed on the outer surface 1462 such that the infusion cannula 1410 is articulated in opposite directions with respect to one or both of the vertical axes B and C, which are arranged along a plane perpendicular to the main axis A. In such examples, two or more sets of features 1460 may be formed on the infusion cannula 1410 on opposing surfaces of the outer surface 1462. In certain embodiments, feature 1460 includes, for example, slots, gaps, or other suitable features etched or cut (e.g., laser-etched or cut) on the outer surface 1462 along the length of the injection cannula 1410 to facilitate biasing the injection cannula 1410 to a curved position.

[0086] The articular movement or flexion of the infusion cannula 1410 can be manually controlled by one or more toggles 1464 separate from the toggle 1440. In certain embodiments, one or more toggles 1464 may be of the same type as toggle 1440. In certain embodiments, one or more toggles 1464 may be of a different type compared to toggle 1440. In Figure 14A, multiple toggles 1464 are arranged around the handle 1402. In such embodiments, each of the multiple toggles 1464 may control the flexion of the infusion cannula 1410 in a different direction. Generally, one or more toggles 1464 may be located within the handle 1402 and coupled to one or more wires that connect to different points inside the infusion cannula 1410, which, when operated by user adjustment of the toggles 1464, act on the infusion cannula 1410, causing the infusion cannula 1410 to articularize in the corresponding direction. Therefore, the manipulation of the wire can generate a curve in the injection cannula 1410 in the desired direction.

[0087] Figure 15A shows a schematic diagram of an exemplary subretinal delivery system 1500 according to a particular embodiment of the present disclosure. The delivery system 1500 may be used, for example, with the delivery device 414 of the surgical system 400 in Figure 4 or with other surgical systems for subretinal injection described herein. The embodiments of the delivery system 1500 may be combined with other delivery devices and / or components described herein, but are not limited.

[0088] Generally, the delivery system 1500 includes an injection needle attached to a conduit, which can be fixed in the eye using a stabilizer so that it is separated from the handle and does not need to be held throughout the procedure. This separates the injection needle from undesirable movements that may occur when the injection instrument is held by hand. Furthermore, the conduit of the delivery system 1500 may be a multi-lumen conduit that provides multiple parallel channels from a separate fluid reservoir to the injection needle, so that in certain examples the injection may be performed using only one needle. The need to insert only one needle through the retina can reduce retinal damage that may otherwise result from repeated punctures of the retina.

[0089] As shown in Figure 15A, the delivery system 1500 generally includes an injection needle 1512, a single 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 certain embodiments, the injection needle 1512 further includes a connector piece 1518 (described in more detail below) at the proximal end 1504 to facilitate 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 connector piece 1518, and a proximal end 1524 attached to the fluid drive system 1570 (e.g., via a handle as described later).

[0090] Figure 15B is an enlarged cross-sectional view taken along the cutting line 15B-15B of Figure 15A, showing an exemplary conduit 1520 having multiple lumens, which is also used in conjunction with other delivery devices and systems described herein. The multi-lumen conduit 1520 has an outer wall 1526o enclosing three lumens 1528a, 1528b, and 1528c. Figure 15B shows three lumens, 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 divided by an inner wall 1526i intersecting the outer wall 1526o. Lumens 1528a-c radially surround the central longitudinal axis 1520x of the conduit 1520. In the embodiment of Figure 15B, one or more of the lumens 1528a-c have different sizes. For example, each of lumens 1528a and 1528b extends circumferentially to one-quarter of the circumference of the conduit 1520. On the other hand, lumen 1528c extends partway circumferentially to the conduit 1520. Therefore, in the embodiment of Figure 15B, the volume of lumen 1528c may be twice the volume of each of lumens 1528a and 1528b. In some other embodiments, each of lumens 1528a-c has the same size.

[0091] Referring here to Figure 15A, the fluid drive system 1570 may include a fluid pump 1572 for driving the flow through the conduit 1520. In certain embodiments, the fluid pump may include a syringe pump, a vernier flow control (VFC) pump or another type of pressure control pump, a volume control pump, a variable volume control pump, a peristaltic pump, a lever-operated pump, a valve-operated pump or a venturi pump. The fluid drive system 1570 further includes one or more fluid reservoirs 1574 for storing one or more fluids for injection. Figure 15A shows three fluid reservoirs 1574, but more or fewer fluid reservoirs can be used. In certain embodiments, each of the fluid reservoirs 1574 may be configured to be actuated by a fluid pump 1572 to drive the flow of the fluid stored therein. Such fluids may include an infusion fluid comprising a non-therapeutic solution, such as an ophthalmic lavage solution having a physiological pH (hydrogen ion concentration) and osmotic pressure (e.g., BSS), and a therapeutic solution, such as a therapeutic substance 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 fluid may also include a working fluid for extending the stabilizer 1560 (e.g., perfluorocarbon solution (PFCL), BSS, physiological saline, air, N2 (nitrogen), other liquids or gases, or combinations thereof).

[0092] The fluid drive system 1570 further includes a controller 1576 for controlling the operation of the fluid pump 1572. In certain embodiments, the controller 1576 includes a wireless receiver that receives commands wirelessly from a control console, such as a surgical console 402. In certain other embodiments, the controller 1576 communicates with the control console via a wired connection.

[0093] Figure 15C is an isometric top view of a portion of the delivery system 1500 of Figure 15A. As shown, the connector piece 1518 has one or more ports 1519 corresponding to one or more lumens of the conduit 1520. In the example of Figure 15C, three ports 1519a, 1519b, and 1519c are shown, each corresponding to and / or located within the distal ends of the respective lumens 1528a-c of the multi-lumen conduit 1520 in Figure 15B. The two separate ports 1519a and 1519b of the connector piece 1518 converge 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 and 1519b. Port 1519c is fluidly coupled to the stabilizer 1560 as shown to facilitate its extension.

[0094] Referring to Figures 15A and 15C, the stabilizer 1560 is shown in an extended position, extending from port 1519c of connector piece 1518. In certain embodiments, the stabilizer 1560 and port 1519c are oriented so that the stabilizer 1560 extends distally from the distal end of connector piece 1518, as shown in Figure 15C. In certain embodiments, the stabilizer 1560 and port 1519c are oriented so that the stabilizer 1560 extends laterally through external port 1564 on the side wall of connector piece 1518. In the extended position, the stabilizer 1560 stabilizes / fixes the injection needle 1512 to the target injection site (i.e., location) on the retinal surface for subretinal injection, thereby reducing the possibility of the injection needle 1512 being dislodged from the subretinal space by accidental light force during the procedure. Stabilization provides further control over the injection location. In the embodiments shown in Figures 15A and 15C, the stabilizer 1560 is a balloon 1562 or a bag. The balloon 1562 may have any suitable shape, including, but is not limited to, circular, oval, or polygonal. The balloon 1562 may be formed from plastic, metal, polymer, nitinol, or a combination thereof.

[0095] Before the stabilizer 1560 is in the extended position, it is positioned within the port 1519c of the connector piece 1518. In certain embodiments, to actuate the stabilizer 1560 to the extended position, a 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, filling the balloon 1562. In certain embodiments, the balloon 1562, and therefore the injection needle 1512, is held in place primarily due to the weight of the working fluid within the balloon 1562.

[0096] In further embodiments, the injection needle 1512 and stabilizer 1560 are held in place via magnetism. For example, the injection needle 1512 may include a magnetic material. By utilizing a magnetic material in the injection needle 1512 in combination with one or more electromagnetic coils or magnets 1550 positioned at desired locations around the patient's head during subretinal treatment, the stability of the injection needle 1512 and stabilizer 1560 can be improved. For example, one or more electromagnetic coils or magnets 1550 can generate a one-dimensional magnetic field that applies a downward force toward the retina to the magnetic injection needle 1512, separate from the gravitational force acting on the injection needle 1512.

[0097] When an electromagnetic coil 1550 is used, it 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 is perpendicular to the circular surface of the coil and can be reversed by changing the direction of the current through the coil. To modify the strength or intensity of the generated magnetic field, the current applied to the electromagnetic coil 1550 can be increased or decreased. The number and position of the electromagnetic coils 1550 may vary depending on the desired positioning of the injection needle 1512 in the patient's eye. In certain embodiments, the electromagnetic coil 1550 may be integrated into a patient head support, patient table, or any suitable device positioned behind the patient's head during the subretinal injection procedure. As described above, a magnet 1550 may be used instead of the electromagnetic coil 1550.

[0098] In further embodiments, the injection needle 1512 and stabilizer 1560 are held in place via negative pressure. For example, in certain embodiments, the connector piece 1518 may include a port 1552 at its distal end. In such embodiments, the port 1552 is 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 1552. Thus, after the injection needle 1512 is positioned at the target injection site on the retinal surface for subretinal injection, the vacuum source may be activated to generate vacuum suction through the port 1552 acting on the retinal surface, thereby fixing the injection needle 1512 and stabilizer 1560 against the retina. Generally, the negative pressure generated by the vacuum source is small enough not to cause any damage to the retina, but large enough to stabilize the injection needle 1512 against the retina.

[0099] Figure 15D is a schematic diagram of the delivery system 1500 of Figure 15A according to embodiments herein, showing an exemplary subretinal delivery device 1501 combined with it. On the other hand, Figure 15E is an enlarged side section view of a portion of Figure 15D, showing an injection needle 1512 used in conjunction with the delivery system 1500 described herein. Figures 15D to 15E are therefore described together herein for clarity.

[0100] Generally, the delivery device 1501 is substantially similar to other subretinal delivery devices herein, except that the 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 space. The delivery device 1501 includes a tubular injection cannula 1510 that directly engages with 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 to surround the conduit 1520.

[0101] The injection cannula 1510 extends from a handpiece 1502 configured to be grasped and handled by a surgeon or surgical assistant. The handpiece 1502 includes an injection needle release toggle 1540 for releasing the injection needle 1512 from the injection cannula 1510 when the injection needle 1512 is properly positioned and secured in the eye. The release toggle 1540 is expected to include any suitable type of mechanical mechanism for releasing the injection needle 1512. For example, in certain embodiments, the release toggle 1540 may include a sliding button or switch that moves the release mechanism, allowing the injection cannula 1510 to disengage from the connector piece 1518, thereby retracting the injection cannula 1510 away from the injection needle 1512.

[0102] In certain embodiments, the infusion cannula 1510 has a slit extending from its proximal end 1516 to its distal end 1514, thus forming a U-shape in its upper cross-section. In such embodiments, the delivery device 1501 is configured to be separated from the conduit 1520 outside the eye by allowing the conduit 1520 to slide through the slit.

[0103] In Figures 15D and 15E, the delivery device 1501 is shown in a configuration ready to initiate a subretinal injection procedure. For example, the delivery device 1501 is coupled to the injection needle 1512, and the injection cannula 1510 of the delivery device 1501 surrounds the conduit 1520. Furthermore, the stabilizer 1560 is in a retracted position located inside the port 1519c of the connector piece 1518, which is positioned within the distal end 1514 of the injection cannula 1510. In certain embodiments, as shown in Figure 15E, the injection cannula 1510 of the delivery device 1501 extends beyond the distal end 1522 of the conduit 1520 and surrounds the connector piece 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 piece 1518. In some embodiments, the inner diameter of the injection cannula 1510 is approximately 0.35 mm to 0.65 mm, such as approximately 0.45 mm to 0.55 mm, and the outer diameter of the connector piece 1518 is approximately 0.4 mm to 0.7 mm, such as approximately 0.5 mm to 0.6 mm. However, other dimensions are also conceivable.

[0104] Figure 15F shows a partial top isometric view of the delivery system 1500 with alternative designs for the injection needle 1582 and stabilizer 1590. In the embodiment of Figure 15F, the stabilizer 1590 is located outside the needle 1582 in both the retracted and extended positions.

[0105] As shown in the figure, the injection needle 1582 has a proximal end 1584 and a distal end 1586. In certain embodiments, the injection needle 1582 further includes a connector piece 1588 extending distally from the proximal end 1584 over a length C shorter than the total longitudinal length N of the injection needle 1582. In some embodiments, the connector piece 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 may be attached to the proximal end 1584 of the injection needle 1582 via the connector piece 1588, while the proximal end 1524 may be attached to a fluid drive system (e.g., via a handle as described later).

[0106] Similar to connector piece 1518, connector piece 1588 has one or more internal ports 1578 corresponding to one or more lumens of conduit 1520. In the example in Figure 15F, two ports 1578a and 1578b are shown, corresponding to the distal ends of lumens 1528a and 1528b, respectively, of the multi-lumen conduit 1520 in Figure 15B, and are configured to fluidly couple with them. The two separate ports 1578a and 1578b of connector piece 1588 converge toward the distal end 1586 of the injection needle 1582.

[0107] The stabilizer 1590 includes a plurality of flexible, bendable legs 1592, which, in certain embodiments, may be oriented to extend along the main longitudinal axis A of the injection needle 1582 when in an “inactive” position. In Figure 15F, three legs 1592 are shown in the “active” position, which provides a three-point stabilization mechanism for stabilizing the injection needle 1582 at the target injection site on the retinal surface, but the use of more legs 1592, such as four, five, six or more legs 1592, is envisioned. Each of the plurality of legs 1592 is coupled proximal to a movable extension ring 1594 surrounding the connector piece 1588 and distal to a fixed base 1596 of the injection needle 1582 adjacent to its distal end 1586. In certain 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, allowing transposition into the subretinal space during injection. The leg portion 1592 is formed of any suitable flexible material, including flexible metals such as nitinol and other metal alloys, and flexible thermoplastic polymer materials such as polyimide, in order to facilitate its bending.

[0108] In this case as well, the stabilizer 1590 is shown in an active position in which the legs 1592 of the stabilizer 1590 are bent and the central portions 1583 of each leg 1592 extend laterally outward from the connector piece 1588. As described above, in certain embodiments, when the legs 1592 are in the inactive position, they may extend substantially parallel to the main longitudinal axis A of the injection needle 1582. To move the stabilizer 1590 from this inactive position to the active position, an extension ring 1594, which may be movable longitudinally along the length C of the connector piece 1588, is actuated distally 1554 (towards the distal end 1586 of the injection needle 1582). The distal movement of the extension ring 1594 causes the legs 1592 to buckle or bend laterally outward from the connector piece 1588 in order to prevent the connector piece 1588 from bending inward. As a result, a suitable three-point support is formed to stabilize 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 to extend the leg portion 1592 longitudinally and thus straighten it. In certain embodiments, the extension ring 1594 can be locked into these inactive and active positions and / or one or more incremental positions in between.

[0109] Generally, a push rod or other suitable mechanism on the infusion cannula of the delivery device can be used to actuate the extension ring 1594 distally 1554 and move the leg 1592 from an inactive position to an active position. For example, before separating the infusion needle 1582 from the infusion cannula of the delivery device (as discussed with reference to Figure 16C below), the user may actuate a toggle on the delivery device handle to move a push rod or other feature on the infusion cannula distally, which in turn acts on the extension ring 1594 and can translate the extension ring 1594 distally. The push rod may interface with the extension ring 1594 via any suitable means such as a hook or clip. In some embodiments, the push rod may be detachably interfaced with the extension ring 1594.

[0110] In some embodiments, the extension ring 1594 may be rotated in a first rotational direction via a pin or other locking mechanism to lock it in the active position. In such embodiments, the extension ring 1594 may be rotated in a second rotational direction opposite to the first rotational direction to facilitate the transition back to the inactive position, thereby unlocking the extension ring 1594 from the pin or other locking mechanism. In some embodiments, the outer diameter of the connector piece 1588 may gradually increase distally, thus allowing the extension ring 1594 to be locked against the connector piece 1588 via mechanical friction. In some embodiments, when transitioning from the active position 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.

[0111] In certain embodiments, the extension ring 1594 may be permanently fixed in a longitudinal position along the connector piece 1588, and the legs 1592 may be configured to rotate around the connector piece 1588, although they are always buckled or bent, to decrease or increase the width of the stabilizer 1590, thereby moving the stabilizer from an inactive or active position, respectively. In such embodiments, to move the stabilizer 1590 to an inactive position, the extension ring 1594 can be rotated in a first rotational direction 1546 to wrap the legs 1592 around the connector piece 1588. To move the stabilizer 1590 to an active position, the extension ring 1594 may be rotated in a second rotational direction 1548 opposite to the first rotational direction 1546. Such rotation of the extension ring 1594 may be achieved, for example, via any suitable rotational mechanism on the injection cannula of the delivery device. In such embodiments, the extension ring 1594 may be rotated to move the leg 1592 to the active position before releasing the injection needle 1582 from the injection cannula 1510 to perform a subretinal injection, and then rotated again to move the leg 1592 to the inactive position after the injection cannula 1510 is reattached to the injection needle 1582 after the subretinal injection has been performed, thus allowing removal from the eye. However, in some embodiments, the injection needle 1582 may be retracted after injection without reattaching the injection cannula 1510 to it, and the leg 1592 may spring back to the inactive position due to its elasticity when removed from the eye, for example in response to contact with a trocar cannula or other entry cannula.

[0112] 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, a pressurized fluid can be used to fill or inflate the legs 1592, and thus extend them laterally from the connector piece 1588. Such a pressurized fluid may be contained within one or more flexible membranes positioned between the legs 1592.

[0113] In further embodiments, the injection needle 1582 and stabilizer 1590 may also be held in place via magnetism and / or negative pressure, as described above with reference to the injection needle 1582. For example, in certain embodiments, the injection needle 1582 may include a magnetic material configured to act upon by a magnetic force applied thereto. In certain 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.

[0114] Figures 16A to 16E show cross-sectional views of an eye 1600 in different steps of performing subretinal injection using the delivery system of Figures 15A to 15E, which has a stabilizer 1560, according to a particular embodiment. Although described and illustrated using stabilizer 1560, the operation of Figures 16A to 16E can also be performed using other stabilization mechanisms, including stabilizer 1580 of Figure 15F.

[0115] Now, returning to Figure 16A, in preparation for subretinal injection, the sclera 1602 is incised using a trocar cannula consisting of a valved insertion cannula 1632 and a trocar, as described above with reference to Figure 2. The trocar is removed from the eye 1600, leaving the valved insertion cannula 1632 in place. Next, the injection cannula 1510 of the delivery device 1501 is inserted into the eye 1600 through 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 target injection site on the surface of the retina 1604 in the subretinal space 1624.

[0116] Subsequently, in Figure 16B, the injection needle 1512 is fixed to the target injection site on the surface of the retina 1604 using a stabilizer 1560. In certain embodiments, pressure or fluid is applied through the lumen of the conduit 1520 (e.g., lumen 1528c) to extend the stabilizer 1560 from the connector piece 1518 and position the stabilizer 1560 in contact with the surface of the retina 1604. The stabilizer 1560 is configured to reliably contact the retina 1604 so that the injection needle 1512 is fixed to the target injection site on the surface of the retina 1604. In certain embodiments, the stabilizer 1560 is formed from a material conforming to the surface of the retina 1604 to increase the contact area between them.

[0117] In embodiments where magnetism is used to stabilize the injection needle 1512, a magnetic field can be provided (e.g., via a coil or magnet) to act on the injection needle 1512 and fix it in place. In embodiments where negative pressure is used to stabilize the injection needle 1512, a vacuum source can be activated, for example, to supply vacuum suction at port 1552.

[0118] In Figure 16C, after the stabilizer 1560 has contacted the surface of the retina 1604, the injection cannula 1510 of the delivery device 1501 is retracted from the eye 1600. In accordance with the retraction of the injection cannula 1510, the injection needle 1512 and conduit 1520 are separated by an external force. As used herein, the external force generally includes any force applied to the injection needle 1512 or conduit 1520 from outside the eye 1600. For example, the external force generally includes light and / or careless movement of any part of the delivery system 1500 or delivery device 1501 by a surgeon or surgical assistant. In certain embodiments, separation limits the effects of external forces associated with the injection and / or external forces associated with the movement of handheld instruments such as the delivery device 1501. In certain embodiments, the extra length of the conduit 1520 is provided unrestricted inside the eye 1600 to facilitate separation. It will be understood that when an external force is applied to the conduit 1520, the extra length allows the conduit 1520 to move within the eye 1600 without transmitting the force to the injection needle 1512.

[0119] In Figure 16D, the injection fluid (e.g., a non-therapeutic solution and / or therapeutic solution) is injected from the fluid-driven system 1570 into the subretinal space 1624 through one or more lumens of the conduit 1520.

[0120] In certain embodiments, the injection fluid is injected in a one-step procedure, which significantly simplifies the fluid handling of the injection fluid and the overall injection procedure. For example, the fluid drive system 1570 may include a fluid reservoir 1574 that stores a mixture of both the therapeutic and non-therapeutic solutions, referred herein as the “premixed” solution. Thus, the fluid pump 1572 can drive a flow of the premixed solution through a single lumen of the 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, a precise dose of the therapeutic substance can be delivered using this one-step method.

[0121] As shown in Figure 16D, in certain embodiments, the injection of a premixed solution forms a bleb 1634 in the subretinal space 1624 between the retina 1604 and the retinal pigment epithelium (RPE) 1630, which is a localized hemispherical elevation of the retina 1604. Since the fluid injected in a one-step procedure contains both a premixed therapeutic solution and a non-therapeutic solution, the dispersion of the injected fluid within the bleb 1634 may be more homogeneous.

[0122] In certain other embodiments, the injection fluid is injected in a two-step procedure, with the non-therapeutic solution and the therapeutic solution being injected separately without pre-mixing. For example, the non-therapeutic solution may first be injected into the subretinal space 1624 from the fluid-driven system 1570 via one of the lumens of the multi-lumen conduit 1520 (e.g., lumen 1528b). This first step can form an initial bleb 1634 within the subretinal space 1624. Subsequently, the therapeutic solution is injected into the subretinal space 1624 from the fluid-driven system 1570 via another lumen of the multi-lumen conduit 1520 (e.g., lumen 1528a), thereby expanding the bleb 1634 from its initial size. The use of this two-step procedure may be particularly beneficial in clinical studies where the ideal or preferred concentration of the therapeutic substance has not yet been determined, as the therapeutic substance is injected gradually and separately from the non-therapeutic solution, thereby providing greater dose flexibility.

[0123] In certain embodiments, the injection of premixed solution or non-therapeutic solution and therapeutic solution is performed hands-free. For example, the fluid pump 1572 can drive the flow of each of the premixed solution, non-therapeutic solution, therapeutic solution and / or working fluid without manually operating a plurality of fluid reservoirs 1574. In certain embodiments, the fluid pump 1572 operates according to commands received from the controller 1576. In certain embodiments, the controller 1576 receives control signals via a wireless receiver. In certain embodiments, the surgeon or surgical assistant may control the pressure or volume of each fluid injection using a foot pedal (e.g., foot pedal 410) that wirelessly communicates with the controller 1576 via a wireless receiver and / or antenna.

[0124] In Figure 16E, after the injection of the injection fluid is complete, the injection needle 1512 may be reactivated by retracting the stabilizer 1560 into the connector piece 1518, thereby removing the stabilizer 1560 from contact with the surface of the retina 1604. In certain embodiments, the working fluid is removed from the stabilizer 1560 and / or the corresponding lumen using vacuum pressure, retracting the stabilizer 1560 therein. In some embodiments, the stabilizer 1560 is removed from contact with the retina 1604 without retracting into the connector piece 1518. In embodiments where magnetism is used to stabilize the injection needle 1512, the magnetic field acting on the injection needle 1512 may be suppressed or deactivated. In embodiments where negative pressure is used to stabilize the injection needle 1512, for example, the vacuum source supplying negative pressure at port 1552 may be deactivated.

[0125] Subsequently, the conduit 1520 and the injection needle 1512 attached thereto may be removed from the eye 1600. In certain embodiments, the injection site may be left unpatched. In some other embodiments, the injection site may be filled with a occlusive agent (e.g., fibrin glue, collagen, cyanoacrylate, cell adhesion factors, fibronectin, laminin, extracellular matrix-based hydrogel, polyacrylic acid, zinc polycarboxylate cement, silicone adhesive, or ophthalmic viscoelastic devices (OVDs), or viscoelastic plugs).

[0126] Figures 17A–17C show cross-sectional side views of exemplary subretinal delivery devices 1700 configured for use in conjunction with an optical coherence tomography (OCT) system to provide OCT guidance during subretinal injection procedures, according to specific embodiments of the present disclosure. The delivery device 1700 may be used, for example, as the delivery device 414 of the surgical system 400 in Figure 4, or as other surgical systems for subretinal injection as described herein. Furthermore, embodiments of the delivery device 1700 may be combined with other delivery devices and / or components described herein, but are not limited.

[0127] Subretinal injection is generally a very delicate procedure because it requires puncturing one or more tissues / membranes of the eye to access the subretinal space, and therefore such a procedure requires considerable skill from the surgeon to minimize trauma. During such a procedure, OCT-based guidance may be used to assist the surgeon and improve its safety. OCT is an imaging technique that uses low-coherence light to capture one-dimensional, two-dimensional, and three-dimensional (e.g., cross-sectional) images with micrometer resolution in real time from within biological tissue. During ophthalmic procedures such as subretinal injection, OCT may be used, among other things, to determine the general structure of the ocular tissue or layer, to measure the distance from the probe tip to the ocular tissue or layer, and / or to measure the thickness of the ocular tissue or layer. Therefore, when used during subretinal injection, OCT can assist the surgeon in accurately positioning the delivery device injection cannula and / or injection needle within the eye for injection.

[0128] Now, returning to Figures 17A and 17B, the delivery device 1700 includes a handle 1702 and a tubular infusion cannula 1710, the proximal end 1716 of the infusion cannula 1710 being coupled to the distal end 1704 of the handle 1702 and extending distally from there. Extending from the distal end 1714 of the infusion cannula 1710 is an inner fluid shaft 1760, within which is a curved or substantially straight infusion needle 1712 (a straight infusion needle 1712 is shown). The infusion needle 1712 is fixedly coupled to the distal end 1762 of the inner fluid shaft 1760, which may have a diameter larger than the diameter of the infusion needle 1712, and extends distally from there. Therefore, in such an embodiment, the distal end 1762 of the inner fluid shaft 1760 can surround the injection needle 1712 over a given length of the proximal end 1706 of the injection needle 1712.

[0129] The internal fluid shaft 1760 is configured to slidably extend from the distal end 1714 of the infusion cannula 1710 and retract into it upon the action of a toggle 1740 on the handle 1702, which may be a sliding toggle. In the embodiments of Figures 17A and 17B, the proximal end 1764 of the internal fluid shaft 1760 is positioned through an internal cavity 1772 of the handle 1702 and fluidly coupled to a slider 1770 (or the base of the toggle 1740) connected to the toggle 1740. The action (sliding in this case) of the toggle 1740 causes translation of the slider 1770 within the handle 1702 and along the main longitudinal axis A of the handle 1702 and the infusion cannula 1710. Therefore, translation of the toggle 1740 in the first distal direction (indicated as arrow 1774) causes the slider 1770 to be translated distally within the cavity 1772, thereby extending the inner fluid shaft 1760 and the injection needle 1712 coupled thereto from 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. On the other hand, translation of the toggle 1740 in the second proximal direction (indicated as arrow 1776) causes the slider 1770 to be translated proximal within the cavity 1772, thereby retracting the inner fluid shaft 1760 and the injection needle 1712 coupled thereto into the injection cannula 1710. Note that the operating mechanisms shown in Figures 17A and 17B are merely illustrative, and other operating mechanisms for translating the slider 1770, such as a deformable basket, button, or equalizer, are also conceivable.

[0130] A flexible fluid conduit 1720 for supplying the injection fluid (e.g., non-therapeutic and / or therapeutic solution) to the delivery device 1700 is positioned through the proximal end 1706 of the handle 1702 and fluid-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 fluid flow during subretinal injection.

[0131] Again, the delivery device 1700 in Figures 17A–17C is configured to be used in conjunction with an OCT system to provide OCT-based guidance during the subretinal injection procedure. To enable OCT imaging during subretinal delivery of the fluid, the optical fiber 1780 is routed through the proximal end 1706 of the handle 1702, through the cavity 1772 and the injection cannula 1710, and terminates distally in the inner fluid shaft 1760 (see Figure 17C in enlarged view). In certain embodiments, as in the example in Figures 17A and 17B, the optical fiber 1780 may extend through the base of the slider 1770 or toggle within the cavity 1772.

[0132] The optical fiber 1780 is coupled to the OCT system 1782, which includes any suitable type of OCT device, such as a time- or frequency-domain OCT device or a Fourier OCT device, and can provide short- 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 in real time. Such OCT imaging can then be used to determine measurements of various individual or collective physical parameters of the patient's eye, including the shapes and thicknesses of various membranes. Furthermore, OCT imaging can be used to determine the distance and / or position of the distal tip 1711 of the injection needle 1712 or the distal ends 1762 and 1714 of the internal fluid shaft 1760 and injection cannula 1710, respectively, to ocular tissue (such as the retina) during ophthalmic procedures. Therefore, visualization using the OCT system 1782 can be used by surgeons during the performance of subretinal injection procedures to guide the placement of the injection needle 1712, such as between the sensory retina and the RPE, without causing unnecessary damage to surrounding tissues, thereby improving the safety and ease of such procedures.

[0133] Now, returning to Figure 17C, the injection needle 1712 and the distal ends 1762 and 1714 of the inner fluid shaft 1760 and the injection cannula 1710, respectively, are shown. In this example, the optical fiber 1780 is positioned through a bore 1766 in the cylindrical wall of the inner fluid shaft 1760 and terminates at its distal end 1762. In certain other embodiments, the optical fiber 1780 may be terminated at any point along the length of the inner fluid shaft 1760, and may be fixedly attached, for example, by adhesive, in a groove on the outer surface of the wall of the inner fluid shaft 1760. Since the inner fluid shaft 1760 is fixedly attached to the injection needle 1712 and translates with it, the distance between the distal end of the optical fiber 1780 and the distal tip 1711 of the injection needle 1712 remains constant during use, thereby enabling continuous and accurate OCT measurements of the distance between the distal tip 1711 and the ocular tissue during the performance of the subretinal injection procedure.

[0134] Figures 18A and 18B show perspective views, respectively, of exemplary subretinal delivery devices 1800 and 1801 according to a particular embodiment of the present disclosure. The delivery devices 1800 and 1801 may be used, for example, as delivery device 414 in the surgical system 400 of Figure 4, and their embodiments may be combined with other delivery devices and / or components described herein, without limitation. Certain embodiments of the delivery devices 1800 and 1801 are particularly useful for performing subretinal injection (and other related procedures) via a suprachoroidal approach, as described above with reference to Figure 3.

[0135] Now, returning to Figure 18A, the delivery device 1800 includes a handle 1802 and a tubular injection cannula 1810 having a proximal end 1816 coupled to the distal end 1804 of the handle 1802 and extending distally therefrom. The distal end 1814 of the injection cannula 1810 includes a distal tip 1811, which in certain embodiments may be tapered or inclined with respect to the main longitudinal axis of the injection cannula 1810 to facilitate the separation of the choroid from the sclera as the injection cannula 1810 moves through the suprachoroidal space. In certain embodiments, the distal tip 1811 may have an elliptical, 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 distal tip 1811 are generally formed from any suitable flexible surgical-grade material, such as metal or thermoplastic polymer material. Examples of flexible metallic materials include nitinol and other metal alloys. An example of a suitable thermoplastic polymer material is polyimide.

[0136] In certain embodiments, the distal tip 1811 is formed from a rigid material, and the remainder of the injection cannula 1810 is formed from a flexible material. In certain embodiments, the distal tip 1811 may include a magnetic material. Combined with one or more electromagnetic coils 1880 positioned at desired locations around the patient's eye, the use of a magnetic material for the distal tip 1811 can enable improved maneuverability of the injection cannula 1810 and distal tip 1811 in the suprachoroidal space for subretinal injection. For example, one or more electromagnetic coils 1880 can be activated to generate a one-dimensional, two-dimensional, or three-dimensional magnetic field and apply force to the magnetic distal tip 1811 to maneuver the distal tip 1811 in the suprachoroidal space, separate from any force applied by the user to the delivery device 1800 to move the distal tip 1811 "forward" (e.g., away from the entry point to the eye, or "scleral incision") through the suprachoroidal space. The magnetic steering of the distal tip 1811 facilitates easier and more precise handling and maneuverability of the distal tip 1811 and the injection cannula 1810 while they are being moved and / or positioned within the suprachoroidal space for subretinal injection. In certain embodiments, the magnetic steering also allows for ergonomic improvements for the surgeon during insertion procedures, as it reduces the physical burden on the surgeon for proper positioning and manipulation of the distal tip 1811 within the suprachoroidal space.

[0137] 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 tip 1811 to steer it in a first lateral direction and a second lateral direction opposite to the first direction, apart from any force that pushes the distal tip 1811 forward. In such embodiments, each of the first and second lateral directions is perpendicular to the main longitudinal axis A of the injection cannula 1810, which is positioned along its longitudinal length, and is also tangential to the superior choroidal space. Furthermore, the one-dimensional force may not be strong or powerful enough on its own to push or pull the distal tip 1811, but rather may be limited to merely assist in steer the distal tip 1811, and any actual movement of the distal tip 1811 is caused by the user manually applying force to the handle 1802.

[0138] In embodiments where two or more electromagnetic coils 1880 are used to generate a two-dimensional or three-dimensional magnetic field, a two-dimensional or three-dimensional force is applied to the magnetic distal tip 1811 to steer it in one or more directions in addition to the first and second lateral directions. In such embodiments, the magnetic distal tip 1811 (and therefore the injection cannula 1810) can be moved through the suprachoroidal space without any force being applied to the handle 1802 by the user; rather, the distal tip 1811 and the injection cannula 1810 can be completely controlled and positioned by the application and modification of the two-dimensional or three-dimensional magnetic field acting on the distal tip 1811.

[0139] Generally, 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 is 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 or intensity 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 be varied depending on the desired insertion direction of the distal tip 1811 and the positioning of the patient's eye. In certain embodiments, the electromagnetic coils 1880 may be integrated with the patient's head support and / or operating table or surgical bed. For example, when integrated with a head support, one coil may be positioned in the head support above the patient's head, one coil may be positioned in the head support behind the patient's head, and another coil may be positioned in the head support on either side of the patient's head.

[0140] In certain embodiments, at least a portion of the distal end 1814 of the injection cannula 1810, such as the distal tip 1811, includes a photoluminescent material, such as a phosphorescent material. For example, in certain embodiments, the distal tip 1811 of the injection cannula 1810 may include a material containing a phosphor, which then emits visible light after being excited by, for example, visible light. The use of a photoluminescent material for the distal tip 1811 (or other portion of the distal end 1814) allows for the visibility of its position through the choroid and retina as the injection cannula 1810 is moved through the suprachoroidal space via a microscope or other viewing system having a viewpoint directed to the retina through the lens or sclera. For example, before inserting the injection cannula 1810 into the patient's eye during a procedure, the distal tip 1811 may be exposed to a visible light source for an appropriate amount of time to energize the photoluminescent material. Subsequently, as the injection cannula 1810 is inserted and moved through the suprachoroidal space, the distal tip 1811 continuously emits light, which can be seen through the choroid and retina using a microscope or other viewing system. Such 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.

[0141] In certain embodiments, the injection cannula 1810 includes an optical fiber 1882 (dashed line) having a distal end 1884 that terminates at or near the distal tip 1811 and is configured to emit light from there. The optical fiber 1882 extends proximal through the injection cannula 1810 and through the handle 1802 and can be optically coupled to any suitable visible light source, such as a white light source inside or outside the handle. For example, the optical fiber 1882 can be optically coupled to a light source integrated with a surgical console. During a subretinal injection procedure, while the injection cannula 1810 is inserted into and moves through the suprachoroidal space, the light source may be operated by the surgeon to emit visible light from the distal end 1884 of the optical fiber 1882, which can be viewed through the choroid and retina using a microscope or other viewing system with a viewpoint directed towards the retina through the lens or sclera. Therefore, the light emitted from the optical fiber 1882 can be used to guide the positioning of the distal end 1814 of the injection cannula 1810 in order to efficiently and accurately position it near the target injection site during subretinal injection procedures. In certain embodiments, the optical fiber 1882 includes a single-core optical fiber, and in certain embodiments, the optical fiber 1882 includes a multi-core optical fiber. Generally, one or more claddings may circumvent or surround one or more cores of the optical fiber 1882.

[0142] As further shown in Figure 18A, a curved or straight injection needle 1812 (a curved needle is shown) is positioned within the injection cannula 1810 to deliver fluid to the subretinal space by perforating the desired ocular tissue (here, the choroid and RPE) at an angle to the main longitudinal axis of the injection cannula 1810. In exemplary embodiments, 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, injection cannulas and injection needles of other sizes / gauges may be used. In certain embodiments, the injection needle 1812 is formed of the same material as the injection cannula 1810 and / or distal tip 1811.

[0143] In certain embodiments, the injection needle 1812 is configured to slidably extend from the distal end 1814 of the injection cannula 1810 and retract into it, thereby facilitating the prevention of damage to the injection needle 1812 during insertion and / or movement of the injection cannula 1810 within the eye. Such operation of the injection needle 1812 can be controlled by any suitable mechanism. In the example of Figure 18A, the operation of the injection needle 1812 is controlled by a toggle 1840 on the handle 1802. In certain embodiments, the toggle 1840 includes a sliding button or switch, wherein sliding the toggle 1840 distally 1842 by the user (e.g., a surgeon) extends the injection needle 1812 from the injection cannula 1810, and sliding the toggle 1840 proximal 1844 retracts the injection needle 1812 into the injection cannula 1810.

[0144] In certain embodiments, the sliding toggle 1840 may also be lockable, thereby allowing the injection needle 1812 to be fixed in either the extended or retracted position. Locking the injection needle 1812 prevents unintended movement of the injection needle 1812 during retinal procedures, such as subretinal injections, thereby reducing the risk of undesirable tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 1840 for adjustment, the toggle 1840 may be continuously pushed down by the user, 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 only be movable while being pushed down by the user (e.g., activated). Correspondingly, when the toggle 1840 is released, the toggle 1840 rises and locks in place, thereby locking the injection needle 1812 in place. Such a push-button locking mechanism may be facilitated in part by one or more tracks, including grooves or notches, along which a spring lever and a toggle 1840 can slide, arranged together with the handle 1802.

[0145] In certain embodiments, the injection needle 1812 is coupled to an internal fluid shaft, at least partially located within the cannula 1810, for fluid coupling between the injection needle 1812 and the toggle 1840 or fluid conduit. In such embodiments, the internal fluid shaft may be slidably positioned within the cannula 1810 to facilitate extension and retraction of the injection needle 1812 when the toggle 1840 is operated.

[0146] In certain embodiments, a flexible fluid conduit 1820 for supplying an injection fluid (e.g., a non-therapeutic solution and / or a therapeutic solution) to the delivery device 1800 is located through the proximal end 1806 of the handle 1802 and may be fluid-coupled to an injection needle 1812 within the handle 1802. In certain 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 (as described elsewhere in this specification). Generally, the fluid conduit 1820 includes a supply line in which a non-therapeutic solution and / or a therapeutic solution from a fluid source can be supplied to the delivery device 1800 for delivery to the eye. In certain embodiments, the fluid source includes a fluid system that may be coupled to the fluid conduit 1820 via a connection 1822 such as a Luer lock or other male-female coupling. In certain other embodiments, the handle 1802 may include an operable internal chamber fluid-coupled to an injection cannula 1810 and containing the injection fluid. In this embodiment, the subretinal delivery device 1800 does not need to be coupled to any external fluid conduit.

[0147] In further embodiments, to simplify the fluid preparation and / or the injection itself for subretinal injection, the therapeutic agent may be supplied to the delivery device 1800 from a pre-filled cartridge (not shown in Figure 18A) which can be coupled to the 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 certain embodiments, the pre-filled cartridge includes a single lumen containing a pre-mixed therapeutic solution containing components mixed in a suitable buffer solution at a desired ratio and / or concentration. Such embodiments facilitate a one-step subretinal injection procedure in which the bleb can be formed with the pre-mixed therapeutic substance, instead of first forming a bleb with a buffer and then injecting the therapeutic substance into the bleb. Thus, utilizing pre-filled and pre-mixed cartridges can facilitate more efficient and precise dose-concentration control. In yet another embodiment, the pre-filled cartridge may include two or more lumens containing unmixed therapeutic substances that can be automatically or semi-automatically mixed, for example, within a fluid system or delivery device, before performing the subretinal injection. Cartridges for therapeutic agents are described in further detail below.

[0148] In certain embodiments, the injection needle 1812 may be further fluid-coupled to a second pre-filled cartridge or other fluid source configured to supply a colorant or marker fluid to the injection needle 1812. In such embodiments, the second pre-filled cartridge or other fluid source may be configured to deliver the colorant or marker fluid to the injection needle 1812 as the needle extends from the injection cannula 1810 and punctures the choroid. Thus, in such embodiments, the colorant or marker fluid may be used to provide visualization of the position of the injection needle 1812 during injection and to prevent the injection needle 1812 from extending beyond the subretinal space into the sensory retina. The colorant or marker fluid may be visualized by the user via a microscope or other viewing system having a viewpoint directed towards the retina through the lens or sclera.

[0149] Returning to Figure 18B, the delivery device 1801 is substantially similar to the delivery device 1800, except for the handle 1803. In Figure 18B, the handle 1803 can be described as a “minimum” handle because its size is reduced to the absolute minimum or near absolute minimum dimension required to extend and retract the injection needle 1812 from the injection cannula 1810. For example, the handle 1803 has a length H which is the minimum length required to facilitate the operation of the toggle 1840 by the user in order to fully extend and retract the injection needle 1812. In Figure 18B, the toggle 1840 has a sliding button, and therefore, length H is the minimum length required to support the toggle 1840 when the injection needle 1812 is translated to a first position where it is fully extended from the cannula 1810 and a second position where it is fully retracted into the cannula 1810.

[0150] In certain embodiments, the handle 1803 is also formed from a lightweight material. For example, the handle 1803 may be formed from a lightweight thermoplastic polymer material that is generally rigid. In certain examples, the handle 1803 includes polyether ether ketone (PEEK), polyether ketone (PEK), and / or polytetrafluoroethylene (PTFE).

[0151] The reduced dimensions and / or lightweight construction of handle 1803 allow the surgeon to shift their focus to the orientation and positioning of the injection cannula 1810 and / or distal tip 1811 during entry and traverse of the suprachoroidal space, rather than handling handle 1803. For example, during conventional subretinal injection using the suprachoroidal approach, the surgeon may simultaneously utilize two sets of forceps: one set for opening and holding the intrascleral incision for entry of the flexible injection cannula of the delivery device, and another set for holding and inserting the injection cannula. If the delivery device includes a large and / or heavy handle, the delivery device must also be supported during the procedure, thereby complicating the procedure as the surgeon only has both hands. In such situations, another member of the surgical staff may need to hold the delivery device while the surgeon guides the injection cannula into the patient's eye. However, the use of a “minimal” handle, such as handle 1803 in Figure 18B, avoids such complexity. Because handle 1803 is small in size and / or light in weight, neither the surgeon nor the surgical assistant needs to hold the handle during the subretinal injection; instead, handle 1803 can be freely suspended, as its size and weight allow the procedure to be performed without interference. Thus, the surgeon can instead concentrate all their attention on manipulating the injection cannula 1810.

[0152] In further embodiments, 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, the patient's head or other body part during the administration of a subretinal injection.

[0153] Figures 19A–19C show various illustrations of exemplary injection cannulas that may be used in conjunction with the delivery devices 1800 and 1801 of Figures 18A–18B or other delivery devices for subretinal injection as described herein, according to a particular embodiment of the present disclosure. More specifically, Figures 19A and 19B show perspective views of straight and curved injection cannulas 1910a and 1910b, respectively, while Figure 19C shows a schematic cross-sectional top view of injection cannula 1910c to demonstrate various exemplary cross-sectional profiles of an injection cannula for use with delivery device 1800.

[0154] As shown in Figure 19A, in certain embodiments, the delivery device 1800 for performing suprachoroidal subretinal injection includes a linear or substantially linear injection cannula 1910a. During such a procedure, to facilitate easy transverse / sliding of the suprachoroidal space, the injection cannula 1910a may be formed from a highly flexible material that allows the injection cannula 1910a to conform to the curvature of the suprachoroidal space once positioned therein, thereby reducing the strain on the choroid caused by the injection cannula 1910a. Thus, the flexibility of the shaft can reduce or eliminate any damage caused to the retina and / or choroid during the positioning of the injection cannula 1910a for subretinal delivery of the fluid.

[0155] In certain embodiments, the injection cannula 1910a is formed from any suitable flexible surgical-grade metal material. Examples of flexible metal materials include nitinol and other metal alloys. In certain embodiments, the injection cannula 1910a is formed from any suitable flexible thermoplastic polymer material. Examples of suitable thermoplastic polymer materials include polyimide, thermoplastic polyurethane (TPU), polyether block amide (PEBA), and the like.

[0156] In certain embodiments, the infusion cannula 1910a includes a width W along its length L that is greater than its vertical height H along its length L. Thus, in such embodiments, the infusion cannula 1910a can be described as substantially "wide" and / or "flat." These dimensions of the infusion cannula 1910a may be advantageous when accessing and traversing the superior choroidal space by distributing strain along the wider surface (width W) of the infusion cannula 1910a, thereby reducing the dilation of the superior choroidal space as the infusion cannula 1910a passes through it, and facilitating a reduction in choroidal and retinal damage. Furthermore, the wide and / or flat morphology of the infusion cannula 1910a allows for better directional control of the infusion cannula 1910a by the user by reducing the lateral flexibility / bendability of the infusion cannula 1910a in the direction parallel to its width W.

[0157] Now, returning to Figure 19B, in a particular embodiment, the delivery device 1800 for performing a suprachoroidal subretinal injection includes a curved injection cannula 1910b. In a particular example, the injection cannula 1910b may be substantially similar to the injection cannula 1910a in terms of material and / or dimensions (e.g., flexible, substantially wide and / or flat), but the injection cannula 1910b includes a predetermined curve C along its length L compared to the linear arrangement of the injection cannula 1910a. In a particular embodiment, the curve C of the injection cannula 1910b matches or substantially matches the curvature of the eye (eye 1900 is illustrated for reference) in the suprachoroidal space 1934, reducing the strain that occurs along the suprachoroidal space 1934 as the injection cannula 1910b passes through it, thereby reducing any damage to the choroid and / or retina. In certain 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 listed above with reference to the injection cannula 1910a. For example, in certain embodiments, the injection cannula 1910b may include aluminum, stainless steel, nitinol, and other metal alloys. In certain embodiments, the injection cannula 1910b may include polyimide, polyurethane (PUR), a combination thereof, or equivalents.

[0158] Figure 19C shows schematic cross-sectional top views (along the main longitudinal axis) of infusion cannulas 1910c–1910e to demonstrate various exemplary cross-sectional profiles of infusion cannulas for use with the delivery device 1800. As shown, on the left, the cross-sectional profile of cannula 1910c has an elliptical shape; in the center, the cross-sectional profile of infusion cannula 1910d has a tablet or rounded rectangular shape; and on the right, the cross-sectional profile of infusion cannula 1910e has a crescent or "u" shape. In all examples, the cross-sectional profiles of infusion cannulas 1910c–1910e further depict the channel 1911 through which the infusion needle, e.g., infusion needle 1912, extends. Note that these cross-sectional profiles in Figure 19C are merely illustrative, and other cross-sectional profiles (including rectangular profiles) for infusion cannulas are also conceivable.

[0159] Figures 20A–20E show various illustrations of another exemplary injection cannula 2010, which may be used with the delivery devices 1800 and 1801 of Figures 18A–18B or other delivery devices for subretinal injection as described herein, according to a particular embodiment of this disclosure. Figures 20A, 20B, and 20C show a top cross-sectional view, a side cross-sectional view, and another side cross-sectional view of the injection cannula 2010, respectively, and Figures 20D and 20E show cross-sectional views of the eye in different steps of performing subretinal injection using the injection cannula 2010. Embodiments of the injection cannula 2010 may be combined with other delivery devices and / or components described herein, but are not limited.

[0160] Now, returning to Figures 20A and 20C, the tubular infusion cannula 2010 includes a distal end 2014 and a proximal end 2016. The proximal end 2016 may be coupled to the handle of any suitable delivery device, such as the handle 1802 of the delivery device 1800 described above. The infusion cannula 2010 further includes a first channel 2011a and a second channel 2011b formed therein, each of which extends from the distal end 2014 or substantially near the distal end 2014 to the proximal end 2016 or substantially near the proximal end 2016. As shown, channels 2011a and 2011b may be separated by one or more walls 2060 of the infusion cannula 2010 or any other suitable means, forming two distinctly different channels within the infusion cannula 2010.

[0161] The injection needle 2012 is slidably coupled within the first channel 2011a and may terminate proximal within the injection cannula 2010 or within the handle at the proximal end 2016 of the injection cannula 2010. Generally, the injection needle 2012 is fluidly coupled directly or indirectly to a fluid source via fluid conduits and / or other connectors to provide the injection fluid (e.g., non-therapeutic solution and / or therapeutic solution) to the injection needle 2012 for subretinal injection.

[0162] On the other hand, the second channel 2011b may be configured to receive or cover the wire 2070. The wire 2070 may be used as a guide wire and / or reinforcing wire during the execution of subretinal injection using the suprachoroidal method. For example, in a particular example, the wire 2070 is configured as a guide wire to guide the injection cannula 2010 to a desired position for injection through the suprachoroidal space. In such an embodiment, the channel 2011b may have an open distal end 2064 for receiving the wire 2070 as the injection cannula 2010 is pushed through the suprachoroidal space (as shown in Figure 20C). Furthermore, the channel 2011b may be connected to a port 2062 located through the outer wall of the injection cannula 2010 near the proximal end 2016 of the injection cannula 2010, through which the wire 2070 can be removed from the channel 2011b after the injection cannula 2010 has been positioned at the final position for subretinal injection. In certain embodiments, the proximal end 2066 of channel 2011b may be open to the inner cavity of the handle which is coupled to the injection cannula 2010, and the wire 2070 may be removed through the handle after the injection cannula 2010 has been positioned in its final location for subretinal injection. The use of wire 2070 as a guide wire is described in further detail below with reference to Figures 20D and 20E.

[0163] In certain embodiments, the wire 2070 is configured as a reinforcing wire to increase the rigidity of the infusion cannula 2010. For example, the wire 2070 may be made from a material having greater rigidity than that of the infusion cannula 2010 and may be inserted into the infusion cannula 2010 to reduce its flexibility during insertion and movement of the infusion cannula 2010 through the suprachoroidal space. In such embodiments, the channel 2011b may have a closed distal end 2064 to maintain the wire 2070 within the channel 2011b as the infusion cannula 2010 moves through the suprachoroidal space (as shown in Figure 20D). Furthermore, in such embodiments, the channel 2011b may also be connected to a port 2062 located near the proximal end 2016 of the infusion cannula 2010. Therefore, before inserting the injection cannula 2010 into the patient's eye and translating the injection cannula 2010 through the suprachoroidal space, the wire 2070 can be inserted into the channel 2011b via port 2062 to increase its rigidity. Also, as described above, after the injection cannula 2010 is positioned in the final location for subretinal injection, the wire 2070 can be removed from the channel 2011b via port 2062 or removed together with the injection cannula 2010 after injection. In other embodiments, the proximal end 2066 of the channel 2011b may be open to an inner cavity of a handle that is coupled to the injection cannula 2010, and the wire 2070 can be inserted into and / or removed from the channel 2011 via the handle.

[0164] In general, wire 2070 may include any suitable material for performing the induction and / or reinforcing functions as described herein. For example, in certain embodiments, wire 2070 includes a metallic material such as stainless steel, aluminum, nitinol, or other metal alloys. In certain other embodiments, wire 2070 includes a thermoplastic polymer such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0165] Returning to Figures 20D and 20E, an exemplary method of using wire 2070 as a guide wire for subretinal injection is shown. In Figure 2D, wire 2070 is inserted into the patient's eye 2030 through the sclera 2032 and guided through the superior choroidal space (SCS) 2034 to the target injection site 2036. Once the distal end of wire 2070 in the superior choroidal space 2034 is positioned adjacent to the target injection site 2036 in the subretinal space 2034, the injection cannula 2010 is inserted onto wire 2070 so that wire 2070 is received within channel 2011b, and the injection cannula 2010 slides along wire 2070 until its distal end 2014 is positioned adjacent to the target injection site. At this point, wire 2070 can be removed from channel 2011b, for example, through port 2062 or the handle of a delivery device coupled to the injection cannula 2010, or wire 2070 may remain in channel 2011b as the injection is performed via injection needle 2012.

[0166] Figures 21A–21C show various illustrations of exemplary distal tip 2111 of an injection cannula according to a particular embodiment of the present disclosure. Specifically, Figures 21A and 21B show perspective views of the distal tip 2111, and Figure 21C shows a schematic cross-sectional side view of the distal tip 2111. The distal tip 2111 is an exemplary distal tip of the delivery devices 1800 and 1801 in Figures 18A–18B or other delivery devices and / or injection cannulas for subretinal injection as described herein. Embodiments of the distal tip 2111 may be combined with other delivery devices and / or components as described herein, but are not limited.

[0167] As shown in Figures 21A to 21C, the distal tip 2111 includes a distal spatula portion 2160 and a proximal body portion 2162. In certain embodiments, the distal tip 2111 further includes a transition portion 2164 positioned between the spatula portion 2160 and the body portion 2162, connecting them. The body portion 2162 is proximal to the injection cannula 2110 of the delivery device.

[0168] In certain embodiments, the spatula portion 2160 has a vertical dimension S (shown in Figure 21C), which is smaller than the vertical dimension B of the body portion 2162. In certain embodiments, the vertical dimensions S and / or B are uniform or substantially uniform along the longitudinal length of the spatula portion 2160 and / or 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 spatula portion 2160 facilitates interlaminar delamination (i.e., separation) of the choroid and sclera as the distal tip 2111 is moved through the suprachoroidal space to the target subretinal injection site. On the other hand, the increased vertical dimension B of the body portion 2162 facilitates the coverage of the extendable injection needle 2112 within the body portion 2162, which may be configured to extend from and retract into a port 2166 formed within the body portion 2162.

[0169] In certain embodiments, the transition portion 2164 has a changing vertical dimension T that increases proximal to the body portion 2162 from the spatula portion 2160. In other words, the vertical dimension T of the transition portion 2164 tapers from the body portion 2162 toward the spatula portion 2162. In certain embodiments, the vertical dimension T of the transition portion 2163 changes linearly along the longitudinal length of the transition portion 2164. In certain embodiments, the vertical dimension T of the transition portion 2164 changes nonlinearly along the longitudinal length of the transition portion 2164, and therefore the transition portion 2164 may have curvature along its longitudinal length. The changing vertical dimension T of the transition portion 2164 results in a gentler increase in vertical thickness between the spatula portion 2160 and the body portion 2162, thereby providing a gentler increase in stress on the choroid and sclera as the distal tip 2111 moves through the suprachoroidal space, reducing damage to such tissues as a result of such movement.

[0170] Generally, the distal tip 2111 may include several different vertical dimensions (e.g., S, T, and B), but in certain embodiments, the distal tip 2111 may include a uniform horizontal transverse dimension H along the longitudinal length of the distal tip 2111 (e.g., perpendicular to the main longitudinal axis A of the distal tip 2111 and / or cannula 2010), as shown in Figures 21A and 21B. However, in certain other embodiments, the distal tip 2111 may include two or more different horizontal transverse dimensions H along the longitudinal length of the distal tip 2111.

[0171] Referring again to Figure 21C, the first side surface 2170 of the distal tip 2111 may be substantially planar and coplanar with the injection cannula 1810, while the second side surface 2172 of the distal tip 2111 opposite the first side surface 2170 may have a stepped, inclined, tapered, or other varying cross-sectional side profile (e.g., along the longitudinal length of the distal tip 2111) as a result of the different vertical dimensions of the spatula portion 2160, the transition portion 2164, and the body portion 2162. In yet another embodiment, as described below in Figures 22A and 22B, the first side surface 2170 may also have a stepped, inclined, tapered, or other variable profile which may be identical or substantially identical to the second side surface 2172. When the distal tip 2111 is moved through the superior choroidal space, the distal tip 2111 is oriented such that the first side surface 2170 faces the sclera (away from the choroid) and the second side surface 2172 faces the choroid.

[0172] As further shown in Figure 21C, the internal lumen 2174 of the distal tip 2111 may have an inclined surface 2180 whose distance from the first side surface 2170 increases distally. This inclined surface 2180 can function as a “slope” to facilitate the extension of the injection needle 2112 from the distal tip 2111 in a direction nonparallel to the main longitudinal axis A of the injection cannula 2110, which is necessary for suprachoroidal subretinal injection, because the injection needle must penetrate the choroid located along the suprachoroidal space (and therefore the injection needle 2112 must extend tangentially with respect to the main longitudinal axis A of the injection cannula 2110). Therefore, as the injection needle 2112 positioned within the injection cannula 2110 extends through its distal tip 2111, the inclined surface 2180 bends the injection needle 2112 upward away from the first side surface 2170, causing it to slide along the inclined surface 2180 until it passes through the port 2166. To facilitate the upward bending of the needle 2112, the needle may contain a flexible material such as nitinol, polyimide, or other suitable flexible surgical-grade material.

[0173] Figures 22A and 22B show various illustrations of exemplary distal tip 2211 of an injection cannula according to a particular embodiment of the present disclosure. Specifically, Figure 22A shows a perspective view of the distal tip 2211, and Figure 22B shows a schematic cross-sectional side view of the distal tip 2211. The distal tip 2211 is another exemplary distal tip for the delivery devices 1800 and 1801 of Figures 18A and 18B, or other delivery devices and / or injection cannulas for subretinal injection as described herein. The embodiments of the distal tip 2211 may be combined with other delivery devices and / or components described herein, but are not limited.

[0174] Similar to the distal tip 2111, the distal tip 2211 includes a distal spatula portion 2260, a proximal body portion 2262, and a transition portion 2264 positioned between the spatula portion 2260 and the body portion 2262, connecting them. In certain embodiments, the body portion 2262 is coupled proximal to the infusion cannula 2110 of the delivery device (shown by a dashed line in Figure 22A). In certain embodiments, the body portion 2262 is coupled proximal to a connector 2268 which may be inserted into the distal end of the infusion cannula 2110 and configured to friction-merge with it in order to couple the distal tip 2211 thereto.

[0175] As shown in Figure 22A, the spatula portion 2260 may have a substantially semicircular and disc-shaped form with a rounded edge 2282. The rounded edge 2282 and semicircular disc shape of the spatula portion 2260 facilitate easier dissection of the choroid from the sclera while reducing damage to such tissue as the distal tip 2211 is moved through the suprachoroidal space to the target injection site. In certain embodiments, the spatula portion 2260 includes a substantially flat (or planar) disc shape, and in certain other embodiments, the spatula portion 2260 includes a curved disc shape that substantially matches the curvature of the suprachoroidal space. On the other hand, the body portion 2262 may have a cylindrical or substantially cylindrical shape, and the transition portion 2264 may have a triangular or slanted shape between the spatula portion 2260 and the body portion 2262.

[0176] The vertical dimension S1 of the semi-circular spatula portion 2260 is smaller than the vertical dimension B1 of the cylindrical body portion 2262. In certain embodiments, the vertical dimensions S1 and / or B1 are uniform or substantially uniform along the longitudinal length of the spatula portion 2260 and / or 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 spatula portion 2260, in conjunction with the rounded edge portion 2282 and its disc-like shape, facilitates easier dissection of the choroid and sclera. On the other hand, the increased vertical dimension B1 of the body portion 2262 facilitates the accommodation of an expandable injection needle 2212 within the body portion 2262, which may be configured to extend from a port 2266 formed in the body portion 2262 and retract into it.

[0177] In certain embodiments, the transition portion 2264 has a changing vertical dimension T1 that increases proximal to the cylindrical body portion 2262, from the disc-shaped spatula portion 2260. In certain embodiments, the vertical dimension T1 of the transition portion 2264 changes linearly along the longitudinal length of the transition portion 2264. In certain embodiments, the vertical dimension T1 of the transition portion 2264 changes nonlinearly along the longitudinal length of the transition portion 2264, and therefore the transition portion 2264 may have curvature along its longitudinal length. The changing vertical dimension T1 of the transition portion 2264 results in a more gradual increase in vertical thickness between the spatula portion 2260 and the body portion 2262, thereby providing a more gradual increase in stress on the choroid and sclera as the distal tip 2211 moves through the suprachoroidal space, thereby reducing damage to such tissues.

[0178] Now, returning to Figure 22B, both the first side 2270 and the second side 2272 of the distal tip 2211 have stepped, inclined, tapered, or other varying cross-sectional side profiles (for example, along the longitudinal length of the distal tip 2211) as a result of the different shapes and thicknesses of the spatula portion 2260, the transition portion 2264, and the body portion 2262. In certain embodiments, the cross-sectional side profiles of the first side 2270 and the second side 2272 are identical. In certain other embodiments, the cross-sectional side profiles of the first side 2270 and the second side 2272 are different. For example, as shown in the embodiment of Figure 22B, the transition portion 2264 may have a steeper incline between the spatula portion 2160 and the body portion 2262 of the first side 2270, and a gentler incline between the spatula portion 2160 and the body portion 2262 of the second side 2272. By utilizing the differences in the profiles of the first side 2270 and the second side 2272, the different vulnerabilities of the choroid and sclera can be explained. For example, when the distal tip 2211 is inserted and moves through the suprachoroidal space, the distal tip 2211 is oriented such that the first side 2270 faces the sclera (away from the choroid) and the second side 2272 faces the choroid. Since the choroid is more delicate than the sclera and the sclera is more robust than the choroid, the first side 2270 may have a steeper transition between the spatula portion 2260 and the body portion 2262, while the second side 2272 may have a gentler transition between the spatula portion 2260 and the body portion 2262.

[0179] As further shown in Figure 22B, similar to the distal tip 2111 described above, the internal lumen 2274 of the distal tip 2211 may also have an inclined surface 2280 whose distance from the first side surface 2270 increases distally. This inclined surface 2280 can act as a slope to facilitate the extension of the injection needle 2212 from the distal tip 2211 in a tangential direction with respect to the main longitudinal axis A of the injection cannula 2210. Thus, when the extendable injection needle 2212 positioned within the injection cannula 2210 is extended through the distal tip 2211, the inclined surface 2280 bends the injection needle 2212 upward away from the first side surface 2270 and causes the injection needle 2212 to slide along the inclined surface 2280 until it passes through the port 2266. In certain embodiments, to facilitate the upward bending of the needle 2212, the needle may contain a flexible material such as nitinol, polyimide, or other suitable flexible surgical-grade material.

[0180] Figures 23A and 23B show a cross-sectional side view of an exemplary internal bevel assembly 2300 for the distal tip of an injection cannula for a subretinal delivery device, according to a particular embodiment of the present disclosure. The bevel assembly 2300 is used in combination with any of the distal tips described herein, including the distal tips 2111 and 2211 described above, to facilitate extension of the injection needle from the distal tip in a tangential or non-parallel direction with respect to the main longitudinal axis of the corresponding injection cannula.

[0181] As shown in Figures 23A and 23B, the internal lumen 2374 of the distal tip 2311 may include an inclined surface 2380 that terminates distally at the port 2366 of the distal tip 2311. In other embodiments described herein, such an inclined surface 2380 may be used to guide a more conventional injection needle upward directly out of the port 2366 and to "bend" it. However, in this embodiment, the injection needle 2312 is instead coupled proximal to a sliding block 2382 that interfacially contacts the inclined surface 2380 of the distal tip 2311 and facilitates the extension and / or retraction of the injection needle 2312 through the port 2366. In certain embodiments, the sliding block 2382 is fabricated from a material that facilitates the easy sliding of the injection needle 2312 with reduced frictional resistance, such as steel, titanium, PEEK (polyether ether ketone), polyoxymethylene (POM), polytetrafluoroethylene (PTFE), or a combination or equivalent thereof.

[0182] The sliding block 2382 is coupled proximal to an internal fluid shaft 2386, which may extend through the injection cannula of the delivery device to its handle. The internal fluid shaft 2386 fluidly couples the sliding block 2382 and the injection needle 2312 directly or indirectly to a fluid source or a fluid conduit connected to the fluid source. Thus, in certain embodiments, the sliding block 2382 includes a fluid channel that facilitates the flow of injection fluid from the internal fluid shaft 2386 to the injection needle 2312, which is fluidly coupled to the sliding block 2382 for delivery to the target subretinal injection site. The internal fluid shaft 2386 may be further coupled to an actuator or other control mechanism located within the handle of the delivery device, which may allow manual operation of the internal fluid shaft 2386 by the user in a proximal or distal direction through the injection cannula of the delivery device.

[0183] In certain embodiments, the sliding block 2382 itself includes a distal inclined surface 2384 that corresponds to (e.g., coincides with or fits) the inclined surface 2380. In certain embodiments, the inclined surface 2384 may be positioned at the same or substantially similar angle as the inclined surface 2380 with respect to the distal tip 2311 or the main longitudinal axis of the injection cannula coupled to the distal tip 2311. When a distal force (pushing force) is applied to the sliding block 2382 from the proximal internal fluid shaft 2386, the inclined surface 2384 interacts with the inclined surface 2380 so that the sliding block 2382 translates upward along the inclined surface 2380 (e.g., slides), thereby extending the injection needle 2312 through the port 2366. Figure 23B shows the inclined surface assembly 2300 in the “extended” position. Similarly, when proximal (tension) force is applied to the sliding block 2382 by the internal fluid shaft 2386, the inclined surface 2384 can interact with the inclined surface 2380 so that the sliding block 2382 translates (e.g., slides) downward along the inclined surface 2380, thereby retracting the injection needle 2312 through the port 2366. Figure 23A shows the inclined surface assembly 2300 in the “retracted” position. Note that although the distal inclined surfaces 2384 and 2380 are shown as planar “inclined” surfaces, other forms of such surfaces, including non-planar and / or curved surfaces, are also conceivable. Furthermore, the inclined surface 2384 may have a different form compared to the inclined surface 2380; for example, the inclined surface 2384 may be round or curved, while the inclined surface 2380 may be planar.

[0184] The described mechanism facilitates the extension and retraction of the injection needle 2312 through the port 2366 without requiring the injection needle 2312 to bend. Therefore, in addition to flexible materials such as polyimide and nitinol, more rigid materials can be used for the injection needle 2312. For example, in certain embodiments, the injection needle 2312 may include metallic materials such as aluminum, stainless steel, nitinol, and other metal alloys. In further embodiments, the injection needle 2312 may include thermoplastic polymer materials such as polyimide, polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0185] In general, the injection needle 2312 can be coupled to the sliding block 2382 at any desired angle or orientation. In the example shown in Figures 23A and 23B, the injection needle 2312 is coupled to the sliding block 2382 at an angle substantially matching the angles of the inclined surfaces 2380 and 2384.

[0186] Figures 24A and 24B show schematic perspective views of another exemplary distal tip 2411 of an injection cannula 2410 for a delivery device according to a particular embodiment of the present disclosure. The distal tip 2411 may be another exemplary distal tip for delivery devices 1800 and 1801 in Figures 18A–18B or other delivery devices and / or injection cannulas for subretinal injection as described herein. Thus, embodiments of the distal tip 2411 may be combined with other delivery devices and / or components described herein, but are not limited.

[0187] Returning to Figure 24A, the distal tip 2411 includes a slotted port 2466 positioned through the side wall 2468 of the distal tip 2411. The slotted port 2466 may be oriented such that the length of the slotted port 2466 along the circumference of the distal tip 2411 is greater than the width of the slotted port 2466 in the longitudinal direction (for example, parallel to the main longitudinal axis A of the injection cannula 2410).

[0188] The injection needle 2412 is located within and extends through the distal tip 2411 and the injection cannula 2410. As shown in Figure 24B, the injection needle 2412 includes a first extension portion 2480 that extends proximally through the entire length of the injection cannula 2410 and can be coupled to an actuator or other suitable control mechanism located on the handle of a delivery device coupled to the injection cannula 2410. The injection needle 2412 further includes a second corkscrew portion 2482 located at the distal end of the injection needle 2412. The corkscrew portion 2482 has a portion of the injection needle 2412 that is preformed to bend or curl along a plane perpendicular to the main longitudinal axis of the extension portion 2480, and as a result, the corkscrew portion 2482 resembles the shape of a corkscrew or spiral. The corkscrew portion 2482 is configured to extend from the slotted port 2466 and retract into it when the extension portion 2480 is rotated, for example, by an actuator or other control mechanism on the delivery device handle. For example, in certain embodiments, the control mechanism may include a rotary knob or dial on the delivery device handle, and rotation of the knob or dial by the user causes rotation of the extension portion 2482, thereby rotating the corkscrew portion 2482 around its axis and extending from the slotted port 2466.

[0189] Similar to the examples in Figures 24A and 24B, the described mechanism facilitates the efficient extension and retraction of the injection needle 2412 through the slotted port 2466 at a tangential angle to the injection cannula 2410 without requiring active bending of the injection needle 2412. Thus, in addition to flexible materials such as polyimide and nitinol, more rigid materials can be used for the injection needle 2412. For example, in certain embodiments, the injection needle 2412 may include metallic materials such as aluminum, stainless steel, and other metal alloys. In further embodiments, the injection needle 2312 may include thermoplastic polymer materials such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0190] Figure 25 shows a schematic perspective view of an exemplary distal tip 2511 of an injection cannula 2510 for a delivery device according to a particular embodiment of the present disclosure. The distal tip 2511 is another exemplary distal tip for delivery devices 1800 and 1801 in Figures 18A–18B or other delivery devices and / or injection cannulas for subretinal injection as described herein. Thus, embodiments of the distal tip 2511 may be combined with other delivery devices and / or components described herein, but are not limited.

[0191] As shown, the distal tip 2511 includes a port 2566 in its side wall 2568 to allow the extension of the extendable injection needle 2512 to enter and exit. In certain embodiments, the distal tip 2511 includes, within its lumen, an inclined or sloped surface that distally terminates at the port 2566 and facilitates the extension of the injection needle 2512 from the port 2566 at a tangential angle with respect to the main longitudinal axis A of the distal tip 2511 and / or the injection cannula 2510.

[0192] In addition to the port 2566 passing through the side wall 2568, the distal tip 2511 further includes a fluid port 2570 located through the distal surface 2572 of the distal tip 2511. The fluid port 2570 may be fluid-coupled to a fluid line or fluid channel extending through the distal tip 2511, the injection cannula 2510, and / or a handle coupled to the injection cannula 2510. The fluid line or channel may include, for example, a flexible fluid conduit, such as a fluid conduit described elsewhere herein for supplying the injection fluid to an injection needle, such as the injection needle 2512. Generally, the fluid line or channel coupled to the fluid port 2570 may be further fluid-coupled to a fluid source for providing a hydrodesection fluid, such as an equilibrium salt solution (BSS) or other suitable fluid. During use, the hydrodissection fluid may flow out of the fluid port 2570 through the fluid line or channel, while the distal tip 2511 moves through the suprachoroidal space to detach or separate the choroid from the sclera, making it easier for the user to position the distal tip 2511 at the target injection site. Therefore, in certain embodiments, the fluid port 2570 is positioned through the distal surface 2572 of the distal tip 2511 so that the hydrodissection fluid flows out from the distal surface 2572 in a direction 2580 parallel or substantially parallel to the main longitudinal axis A of the distal tip 2511 and / or the injection cannula 2510.

[0193] Returning to Figures 26A and 26B, another exemplary subretinal delivery device 2600 according to a particular embodiment of the present disclosure is shown in various perspective views. The delivery device 2600 is substantially similar to the delivery device 1800 and may be used, for example, as the delivery device 414 of the surgical system 400 in Figure 4. Embodiments of the delivery device 2600 may be combined with other delivery devices and / or components described herein, but are not limited. A particular embodiment of the delivery device 2600 is particularly useful for performing subretinal injection (and other related procedures) via a suprachoroidal approach, as described above with reference to Figure 3.

[0194] As shown, the delivery device 2600 includes a handle 2602 and a tubular injection cannula 2610 having a proximal end 2616 coupled to the distal end 2604 of the handle 2602 and extending distally therefrom. The distal end 2614 of the injection cannula 2610 includes a distal tip 2611 that may be tapered or inclined with respect to the main longitudinal axis of the injection cannula 2610 to facilitate the separation of the choroid from the sclera as the injection cannula 2610 moves through the suprachoroidal space. In certain embodiments, the distal tip 2611 may have an elliptical, broadened, or flat cross-section to facilitate easier translation through the suprachoroidal space. Exemplary distal tips are discussed in more detail elsewhere in this specification. The injection cannula 2610 and / or distal tip 2611 are generally formed from any suitable flexible surgical-grade material, such as flexible metal or thermoplastic polymer material. Examples of flexible metallic materials include nitinol and other metal alloys. An example of a suitable thermoplastic polymer material is polyimide. In certain embodiments, the distal tip 2611 is formed from a rigid material, and the remainder of the injection cannula 2610 is formed from a flexible material.

[0195] As further shown in Figures 26A and 26B, a curved or straight injection needle 2612 is positioned within the injection cannula 2610 to deliver fluid to the subretinal space by perforating the desired ocular tissue (here, the choroid and RPE) at an angle to the main longitudinal axis of the injection cannula 2610. In exemplary embodiments, 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, injection cannulas and injection needles of other sizes / gauges may be used. In certain embodiments, as described elsewhere in this specification, the injection needle 2612 is formed from a flexible material such as nitinol or polyimide. In certain embodiments, the injection needle 2612 is formed from a metallic material such as stainless steel or a rigid material including a thermoplastic polymer such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0196] In certain embodiments, the injection needle 2612 is configured to slidably extend from the distal end 2614 of the injection cannula 2610 and retract into it, thereby facilitating the prevention of damage to the injection needle 2612 during insertion and / or movement of the injection cannula 2610 within the patient's eye. Such operation of the injection needle 2612 can be controlled by any suitable control mechanism. In Figure 26A, the operation of the injection needle 2612 is controlled by a first toggle 2640 on the handle 2602. In certain embodiments, the toggle 2640 includes a sliding button or switch, wherein sliding the toggle 2640 distally 2642 by the user (e.g., a surgeon) extends the injection needle 2612 from the injection cannula 2610, and sliding the toggle 2640 proximal 2644 retracts the injection needle 2612 into the injection cannula 2610. In certain embodiments, the injection needle 2612 is coupled to an internal fluid shaft, at least partially located within the cannula 2610, for fluid coupling of the injection needle 2612 to a fluid conduit or for coupling the injection needle 2612 to a toggle 2640. In such embodiments, the internal fluid shaft may be slidably located within the cannula 2610 to facilitate extension and retraction of the injection needle 2612 when the toggle 2640 is operated.

[0197] In certain embodiments, the sliding toggle 2640 may also be lockable, thereby allowing the injection needle 2612 to be fixed in either the extended or retracted position. Locking the injection needle 2612 prevents unintended movement of the injection needle 2612 during retinal procedures, such as subretinal injections, thereby reducing the risk of undesirable tissue damage and improving the overall safety of such procedures. In one example, to unlock / release the sliding toggle 2640 for adjustment, the toggle 2640 may be continuously pushed down by the user, 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 only be movable while being pushed down by the user (e.g., activated). Correspondingly, when the toggle 2640 is released, the toggle 2640 rises and locks in place, thereby locking the injection needle 2612 in place. Such a push-button locking mechanism may be facilitated in part by one or more tracks, including grooves or notches, along which a spring lever and a toggle 2640 can slide, arranged together with the handle 2602.

[0198] As further shown in Figure 26A, in certain embodiments, a flexible fluid conduit 2620 for supplying an injection fluid (e.g., a non-therapeutic solution and / or therapeutic solution) to the delivery device 2600 is located through the proximal end 2606 of the handle 2602 and may be fluid-coupled to an injection needle 2612 within the handle 2602. In certain 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 in this specification). Generally, the fluid conduit 2620 includes a supply line that can provide the injection fluid (non-therapeutic solution and / or therapeutic solution) from a fluid source (not shown in Figure 26A) to the delivery device 2600 for delivery to the eye. In certain embodiments, the fluid source includes a fluid system that may be coupled to the fluid conduit 2620 via a connection 2622 such as a Luer lock or other male-female coupling. In certain other embodiments, the handle 2602 may be fluid-coupled to the injection cannula 2610 and include an operable internal chamber (not shown in Figure 26A) for containing the injection fluid. In such embodiments, the subretinal delivery device 2600 does not need to be coupled to any external fluid conduit.

[0199] In further embodiments, to simplify the fluid preparation and / or the injection itself for subretinal injection, the therapeutic agent may be supplied to the delivery device 2600 from a pre-filled cartridge that can be coupled to a fluid system connected to the delivery device 2600 either directly to the delivery device 2600 or via a fluid conduit 2620. Cartridges for therapeutic agents are described in more detail elsewhere in this specification.

[0200] The delivery device 2600 further includes a reinforcing sleeve 2670. The reinforcing sleeve 2670 is slidably coupled to the infusion cannula 2610 and, in the embodiments of Figures 26A and 26B, substantially surrounds at least a portion of the infusion cannula 2610. However, in certain other embodiments, a reinforcing sleeve 2700 may be located within the infusion cannula 2610 and function substantially similarly.

[0201] The reinforcing sleeve 2670 is adjustable relative to the infusion 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 (shown in Figure 26B) of the infusion cannula 2610 outside the handle 2602. Thus, the user can selectively adjust (e.g., increase or decrease) a certain level of stiffness of the infusion cannula 2610 by adjusting the position of the reinforcing sleeve 2670 relative to the distal end 2614 of the infusion cannula 2610, and thus manipulating the amount of support provided to the infusion cannula 2610, thereby stabilizing the infusion cannula 2610 during its use. Therefore, the reinforcing sleeve 2670 allows for the option of increasing the stiffness of the infusion cannula 2610 for easier entry and access to the suprachoroidal space, while also allowing for the option of decreasing the stiffness of the infusion cannula 2610 once it enters the suprachoroidal space to facilitate the adaptation of the infusion cannula 2610 to the curvature of the patient's eye, thereby reducing stress on the choroid and sclera. For example, the reinforcing sleeve 2670 can be fully extended to increase the stiffness of the infusion cannula 2610 before / during its entry into the suprachoroidal space, thereby facilitating its better control and / or operability and improving overall safety and ease of use. Once inserted into the suprachoroidal space, the reinforcing sleeve 2670 can be retracted to decrease the stiffness of the infusion cannula 2610. For example, the reinforcing sleeve 2670 can be retracted as the infusion cannula 2610 is further pushed into the suprachoroidal space to promote the flexibility of the infusion cannula 2610 within the suprachoroidal space, thereby reducing stress and damage to the choroid, including the risk of choroidal hemorrhage.

[0202] The reinforcing sleeve 2670 is generally a cylindrical hollow tube that substantially surrounds the proximal end 2616 of the infusion cannula 2610 or a portion near it. In certain embodiments, the reinforcing sleeve 2670 has uniform transverse dimensions along its longitudinal or axial length, thereby resembling a simple cylinder. In certain embodiments, the reinforcing sleeve 2670 may have non-uniform transverse dimensions along its longitudinal or axial length, resembling a tapered cylinder. The reinforcing sleeve 2670 is generally formed from a suitable surgical-grade material having adequate stiffness to provide increased rigidity or support to the infusion cannula 2610. In certain embodiments, the reinforcing sleeve 2670 is formed from a metallic material such as stainless steel, aluminum, or titanium. In certain embodiments, the reinforcing sleeve 2670 is formed from a composite material such as a thermoplastic polymer composite or a ceramic composite. For example, the reinforcing sleeve 2670 may include polyether ether ketone (PEEK), polyether ketone (PEK), and / or polytetrafluoroethylene (PTFE). In certain embodiments, the reinforcing sleeve 2670 includes polycarbonate (PC).

[0203] Together with the infusion cannula 2610, the reinforcing sleeve 2670 is movably positioned through an opening 2672 at the distal end 2604 of the handle 2602. The proximal end of the reinforcing sleeve 2670 is positioned within the internal chamber or lumen of the handle 2602. The reinforcing sleeve 2670 is sized to have a sufficient longitudinal (i.e., axial) length to provide the infusion cannula 2610 with the desired rigidity and stability, while a portion of the reinforcing sleeve 2670 remains inside the handle 2602 when it is fully extended or stretched.

[0204] As described above, the reinforcing sleeve 2670 is configured to slidably extend from the opening 2672 of the handle 2602 and retract into it. Such operation of the reinforcing sleeve 2670 can be controlled by any suitable control mechanism. In Figure 26A, the operation of the reinforcing sleeve 2670 is shown as being controlled by a second toggle 2674 on the handle 2602. In certain embodiments, the toggle 2674 includes a sliding button or switch similar to the toggle 2640, where sliding the toggle 2674 distally 2642 by the user extends the reinforcing sleeve 2670 from the opening 2672, and sliding the toggle 2674 proximal 2644 retracts the reinforcing sleeve 2670 into the opening 2672. Alternatively, if the toggle 2674 includes a push button, the extension and / or retraction of the reinforcing sleeve 2670 can be controlled via pressing or releasing the toggle 2674.

[0205] In certain embodiments, the toggle 2674 may also be lockable so that the reinforcing sleeve 2670 can be fixed in place along length L during user adjustment. In certain examples, the toggle 2674 may be lockable to one or more preset positions corresponding to incremental preset positions of the reinforcing sleeve 2670 along length L of the injection cannula 2610, such preset positions of the reinforcing sleeve 2670 further corresponding to predetermined levels of stiffness of the injection cannula 2610. Locking the reinforcing sleeve 2670 prevents unintended movement of the reinforcing sleeve 2670 during surgical procedures, such as subretinal injections, thereby reducing the risk of accidentally over-stiffening or under-stiffening the injection cannula 2610 while positioning it in the patient's eye. In a particular example where the toggle 2674 is a sliding button, the toggle 2674 may be continuously pressed down by the user to unlock / release the toggle 2674 for adjustment, allowing the user to freely slide the toggle 2674 and thus freely extend or retract the reinforcing sleeve 2670. In this example, the toggle 2674 may only be movable while being pressed down (e.g., activated) by the user. Correspondingly, by releasing the toggle 2674, the toggle 2674 can be raised and locked in place, thereby locking the reinforcing sleeve 2670 in place. Such a locking mechanism may be facilitated in part by the use of a spring lever located with the handle 2602 and one or more tracks including grooves or notches along which the toggle 2674 can slide.

[0206] Figures 27A and 27B show various perspective views of another exemplary subretinal delivery device 2700 according to a particular embodiment of the present disclosure. The delivery device 2600 is substantially similar to the delivery devices 1800 and 2600 and may be used, for example, as the delivery device 414 of the surgical system 400 in Figure 4. Embodiments of the delivery device 2700 may be combined with other delivery devices and / or components described herein, but are not limited to them. Similar to the earlier delivery device 2600, a particular embodiment of the delivery device 2700 is particularly useful for performing subretinal injections (and other related procedures) via a suprachoroidal approach, as described above with reference to Figure 3. More specifically, the embodiment of the delivery device 2700 facilitates improved ergonomics for the user, as the delivery device 2700 may be held horizontally rather than vertically during the execution of such injections during suprachoroidal subretinal injections.

[0207] As shown in Figure 27A, the delivery device 2700 includes a handle 2702 for holding by the user. In certain embodiments, a flexible fluid conduit 2720 for supplying the injection fluid to the delivery device 2700 may be located through the proximal end 2706 of the handle 2702 and fluid-coupled to a tubular injection cannula 2710 within the handle 2702. In certain embodiments, the fluid conduit 2720 may be coupled to the proximal end 2706 of the handle 2702 or to another fluid conduit (described elsewhere in this specification) within the handle 2602. In certain other embodiments, the handle 2702 may include an operable internal chamber (not shown in Figure 27A) fluid-coupled to the injection cannula 2710 and containing the injection fluid. In such embodiments, the subretinal delivery device 2700 does not need to be coupled to any external fluid conduit. In further embodiments, to simplify the fluid preparation and / or the injection itself for subretinal injection, the therapeutic agent or other injection fluid may be supplied to the delivery device 2700 from a pre-filled cartridge that can 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 a fluid conduit 2720. Cartridges for therapeutic agents are described in more detail elsewhere in this specification.

[0208] The proximal end 2776 of the curved shaft adapter 2770 connects to the distal end 2704 of the handle 2702 and extends from there. The curved shaft adapter 2770 allows the user to hold the delivery device 2700 horizontally rather than vertically during subretinal injection or other procedures, thereby facilitating improved stability, control, and overall safety when using the delivery device 2700. Furthermore, when the delivery device 2700 is held horizontally by the user, it does not interfere with the optics of any visualization system being used, such as a microscope. Thus, the curved shaft adapter 2770 facilitates improved ergonomics for the user when using the delivery device 2700. In certain embodiments, the curved shaft adapter 2770 includes a curved, curled, or bent hollow tube.

[0209] The shaft adapter 2770 can be defined by any suitable curvature for performing subretinal injection via the suprachoroidal method. For example, in certain embodiments, the shaft adapter 2770 has a radius of curvature R of 1 mm to about 20 mm, for example, about 5 mm to about 15 mm, for example, about 10 mm. In certain embodiments, due to the curvature of the shaft adapter 2770, the distal end 2774 of the shaft adapter 2770 has a principal axis S positioned at an angle of 0 to 90 degrees with respect to the principal longitudinal axis A of the handle 2702. For example, in certain embodiments, the principal axis S (and the principal longitudinal axis of the cannula 2710) is positioned at an angle of 30 to 60 degrees with respect to the principal axis A, such as an angle of 45 degrees with respect to the principal axis A. In certain embodiments, the principal axis S (and the principal longitudinal axis of the cannula 2710) is positioned at an angle of 45 to 90 degrees with respect to the principal axis A, such as an angle of about 60 to 75 degrees with respect to the principal axis A. Generally, the curvature of the shaft adapter 2770 is such that any conduits and / or fluids within the shaft adapter 2770 are not adversely affected by the curvature (for example, the curvature does not cause them to twist or slide), and 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.

[0210] In certain embodiments, the curved shaft adapter 2770 may be formed from a rigid material, such as a rigid metal or polymer material. Examples of rigid metal materials include stainless steel, aluminum, and titanium.

[0211] The proximal end 2716 of the extendable infusion cannula 2710 is coupled to the distal end 2774 of the shaft adapter 2770. The extendable infusion cannula 2710 is configured to slidably extend from the distal end 2774 of the shaft adapter 2770 and retract into it, thereby allowing the infusion cannula 2710 to extend through the superior choroidal space to the target injection site after it has been inserted into the patient's eye. Such operation of the infusion cannula 2710 can be controlled by any appropriate control mechanism. In Figure 27A, the operation of the infusion cannula 2710 is controlled by a toggle 2740 on the handle 2702. In certain embodiments, the toggle 2740 includes a sliding button or switch, wherein user sliding of the toggle 2740 distally 2742 extends the infusion cannula 2710 from the shaft adapter 2770, and sliding of the toggle 2740 proximally 2744 retracts the infusion cannula 2710 into the shaft adapter 2770.

[0212] The injection cannula 2710 further includes a distal tip 2711 located at its distal end 2714. In certain embodiments, the distal tip 2711 may have a tapered or inclined (e.g., slanted) profile to facilitate movement through the suprachoroidal lumen. In certain embodiments, the distal tip 2711 may have an elliptical, broadened, or flat cross-section to facilitate easier translation through the suprachoroidal lumen. Exemplary distal tips are discussed in more detail elsewhere in this specification. The injection cannula 2710 and / or distal tip 2711 are generally formed from any suitable flexible surgical-grade material, such as flexible metal or thermoplastic polymer material. Examples of flexible metallic materials include nitinol and other metal alloys. Examples of suitable thermoplastic polymer materials include polyimide. In certain embodiments, the distal tip 2711 is formed from a rigid material, and the remainder of the injection cannula 2710 is formed from a flexible material.

[0213] Now, returning to Figure 27B, the curved or straight injection needle 2712 is coupled to the distal tip 2711. In certain embodiments, the injection needle 2712 is configured to slidably extend from the distal tip 2711 and retract inward, which facilitates the prevention of injury to the injection needle 2712 and / or the patient's eye during the movement of the injection cannula 2710 through the suprachoroidal space. Such extension / retraction of the injection needle 2712 can be controlled by any suitable control mechanism, such as a toggle on a 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, injection cannulas and injection needles of other sizes / gauges may be used.

[0214] In certain embodiments, the injection needle 2712 is formed of a flexible material such as nitinol or polyimide, as described elsewhere in this specification. In certain embodiments, the injection needle 2712 is formed of a metallic material such as stainless steel or a rigid material including a thermoplastic polymer such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE).

[0215] Figures 28A to 28D show various illustrations of exemplary induction cannulas 2800 according to specific embodiments of the present disclosure. Induction cannulas 2800 can be used in combination with other delivery devices described herein, for example, delivery devices 1800 and 1801 in Figures 18A to 18B. Thus, embodiments of induction cannulas 2800 can be combined with other delivery devices and / or components described herein without limitation.

[0216] Generally, a guide cannula 2800 includes an expandable, flexible cannula configured to provide a predetermined channel through which an injection cannula of a delivery device can be inserted to be guided and translated to the target injection site via the suprachoroidal space. For example, the guide cannula may be initially inserted into the patient's eye and advanced through the suprachoroidal space until its distal end is positioned adjacent to the target injection site. The guide cannula may then be expanded, and the injection cannula may be inserted into and advanced through the expanded guide cannula until the distal end of the injection cannula reaches the target injection site (for example, until the distal end of the injection cannula passes the distal end of the guide cannula). Thus, the guide cannula facilitates easier handling and positioning of the injection cannula during its entry and positioning within the suprachoroidal space. Furthermore, since the guide cannula does not require an injection needle or any fluid dynamics, the guide cannula may have a smaller lateral dimension compared to the injection cannula of the delivery device. Therefore, the guide cannula can reduce the strain on the choroid during its insertion, thereby reducing overall damage to the choroid during suprachoroidal subretinal injection.

[0217] Returning to Figure 28A, a cross-sectional side view of the induction cannula 2800 is shown. As shown, the induction cannula 2800 includes a hub 2870 and a tube 2880. The tube 2880 is coupled to the bottom (e.g., distal) surface 2872 of the hub 2870 and extends distally therefrom. The tube 2880 is configured to be inserted into and pass through the suprachoroidal space of the patient's eye, and further configured to facilitate the insertion and advancement of the infusion cannula into it. Thus, in certain embodiments, the tube 2880 may be substantially tubular with a circular, elliptical, or tablet-shaped upper cross-sectional profile (e.g., when viewed along the longitudinal length of the tube 2880). However, other apical cross-sectional morphologies for the tube 2880 are also conceivable, as will be described below. Furthermore, the tube 2880 includes a centrally located guide channel 2882 that extends from an opening 2851 at its proximal end 2853 to an opening 2855 at its distal end 2857. The guide channel 2882, as well as the openings 2851 and 2855, allow the injection cannula to pass through both ends of the tube 2880.

[0218] On the other hand, the hub 2870 may be substantially cylindrical or ring-shaped in certain embodiments, but other forms are also conceivable. The hub 2870 includes a central channel 2878 which is fluidly coupled to the opening 2851 of the guide channel 2882 and further surrounded and partially defined by the inner wall 2897 of the hub 2870. In certain embodiments, the hub 2870 may function as a stopper or retaining device to prevent the tube 2880 from entering too deeply into the suprachoroidal space during insertion. Thus, the bottom surface 2872 of the hub 2870 may be configured to be coplanar 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. In addition, the hub 2870 may act as an adapter to facilitate easier insertion of the infusion cannula into the tube 2880. Therefore, the upper (e.g., proximal) surface 2874 and / or inner wall 2897 may have an inclined, sloped and / or conical shape to mechanically guide the injection cannula into the guidance channel 2882 of the tube 2880.

[0219] In certain embodiments, the hub 2870 and the tube 2880 are formed monolithically so that they contain the same material. For example, both the hub 2870 and the tube 2880 may be formed from flexible and expandable materials such as silicone, polyurethane (PUR), polyether block amide (PEBA), polyolefins, combinations thereof, and equivalents. In certain other embodiments, the hub 2870 and the tube 2880 may contain different materials. For example, the hub 2870 may be formed from a rigid or non-expandable material such as a metallic material such as stainless steel, aluminum, titanium, or other metal alloys, or the hub 2870 may be formed from a thermoplastic polymer such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE), while the tube 2880 may be formed from a flexible / elastic and expandable material such as plastic, metal, polymer, nitinol, or combinations thereof.

[0220] As further shown in Figure 28A, in certain embodiments, the hub 2870 and / or tube 2880 include an expansion channel 2890. The expansion channel 2890 may be located within the wall 2876 of the hub 2870 and / or the wall 2886 of the tube 2880. In certain embodiments, the expansion channel 2890 surrounds at least a portion of a guide channel 2882 formed in the center of the tube 2880. In certain embodiments, the expansion channel 2890 surrounds the entire or substantially entire longitudinal length of the guide channel 2882 formed in the center of the tube 2880. In certain embodiments, the channel 2890 is fluid-coupled to a closable port 2892 formed in the hub 2870 and / or tube 2880. The closable port 2892 allows entry into and exit from the channel 2890 from outside the guide cannula 2800. Therefore, channel 2890 may be filled with a fluid to expand tube 2880 (or hub 28170 in certain embodiments), thereby increasing at least the lateral dimension (e.g., diameter) of tube 2880, and consequently the lateral dimension (e.g., diameter) of the induction channel 2882, thereby facilitating the entry and passage of the injection cannula of the delivery device through tube 2880. In certain embodiments, channel 2890 may be filled with a gas such as air, oxygen, nitrogen (N2), or other gases. In certain embodiments, channel 2890 may be filled with a liquid such as perfluorocarbon solution (PFCL), BSS, saline solution, or other liquids. In certain embodiments, channel 2890 may be filled with a combination of liquid and gas.

[0221] However, in certain embodiments, the tube 2880 may be expanded by other means, including mechanical means. For example, in certain embodiments, the tube 2880 may be expanded by utilizing the inherent spring-like action of the braided wire when the braided wire is twisted by the user. The braided wire may be placed in an expansion channel 2890 within the wall 2886 of the tube 2880, or the braided wire may be placed in a guide channel 2882 and circumferentially lined. Furthermore, other mechanical means for expanding the tube 2880 are also conceivable.

[0222] In certain embodiments, the induction cannula 2800 may not include a separate expansion mechanism or device other than being formed of a flexible material. For example, in such embodiments, the tube 2880 may have an outer diameter larger than the lateral dimension (e.g., diameter) of the induction channel 2882 and may be potentially expanded by the insertion of an injection cannula through it. Thus, the tube 2880 may expand as the injection cannula advances through the tube 2880.

[0223] In certain embodiments, the expandability of tube 2880 can be optimized based on its cross-sectional profile. For example, in certain embodiments, tube 2880 may have a star-shaped cross-sectional profile or other appropriately shaped profile such that the expansion of tube 2880 is not caused by stretching of wall 2886, or in addition, by the "unfolding" of wall 2886. An exemplary cross-sectional top view of a star-shaped cross-sectional profile of tube 2880 is shown for reference in Figure 28B. The unfolding 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 in use.

[0224] Figures 28C and 28D show schematic cross-sectional side views of an exemplary guide cannula 2800 in use. In Figure 28C, the guide cannula 2800 is first 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 tube 2880 is positioned adjacent to the target injection site 2808. Subsequently, in Figure 28D, the guide cannula 2800 may be expanded by flowing fluid into the expansion channel 2890 (and sealing the closable port 2892), etc. The injection cannula 2810 of the delivery device 2802 can then be inserted into the expanded guide cannula 2800 until the distal end of the injection cannula 2810 passes the distal end 2857 adjacent to the target injection site 2808, and advanced through it, more specifically, through the tube 2880. At this point, the injection needle of the injection cannula 2810 can be extended to puncture the choroid in order to inject fluid into the subretinal space.

[0225] Figures 29A–29C show various illustrations of exemplary entry cannula 2900 according to a particular embodiment of the present disclosure. Entry cannula 2900 is an exemplary entry cannula that can be used to facilitate the entry of an injection cannula of a delivery device into the suprachoroidal space through the sclera of the eye, as described above with reference to Figure 3. Thus, entry cannula 2900 can be used in combination, for example, with delivery devices 1800 and 1801 in Figures 18A–18B, delivery device 2600 in Figure 26, and other delivery devices for subretinal injection described herein. However, embodiments of entry cannula 2900 may be combined with other delivery devices and / or components described herein, without limitation.

[0226] Returning to Figure 29A, the entry cannula 2900 includes a tubular body 2902 having a central channel 2908 extending from the proximal end 2904 of the body 2902 to the distal end 2906 of the body 2902. After the entry cannula 2900 is inserted through the sclera of the patient's eye, the central channel 2908 functions as an entry point or port for the subsequent insertion of the infusion cannula of the delivery device. Thus, the central channel 2908 may have a transverse dimension (e.g., diameter) along its longitudinal length that is substantially the same as or greater than that of the infusion cannula inserted through it. In certain embodiments, the central channel 2908 has a uniform dimension from the proximal end 2904 to the distal end 2906. In certain embodiments, the central channel 2908 has non-uniform transverse dimensions from the proximal end 2904 to the distal end 2906, for example, the central channel 2908 may have a larger transverse dimension at or near the proximal end 2904 compared to the distal end 2906.

[0227] In certain embodiments, the body 2902 may have a substantially circular cross-sectional profile. In certain other embodiments, as shown in Figure 29A, the body 2902 may have a “flattened” cross-sectional profile that may resemble an ellipse or oblong or a pill or rounded rectangle.

[0228] In certain embodiments, the body 2902 includes a distal spatula portion 2960 including a distal end 2906 and a proximal entry portion 2962 including a proximal end 2904. Generally, the spatula portion 2960 may have a beveled or wedge-shaped form such that the vertical dimension S1 of the spatula portion 2960 at the distal end 2906 gradually transitions proximal to the vertical dimension S2 of the spatula portion 2960. The beveled or wedge-shaped form facilitates choroidal dissection (i.e., separation) as the distal end 2906 of the entry cannula 2900 advances into the suprachoroidal space after passing through the sclera of the patient's eye. In certain embodiments, the spatula portion 2960 includes a notch 2963 formed in the side wall of the body 2902 that fluidly couples with a central channel 2908 and improves the efficiency of interlaminar dissection.

[0229] In certain embodiments, the spatula portion 2960 is formed from a rigid material including a metallic material such as aluminum, stainless steel, and other metal alloys, or a thermoplastic polymer material such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE). In certain other embodiments, the spatula portion 2960 is formed from a flexible material including a metallic material such as nitinol and a thermoplastic polymer material such as polyimide. By utilizing a flexible material for the spatula portion 2960, distortion of the choroid, retina, and / or sclera during insertion of the entry cannula 2900 can be reduced, thereby reducing damage to the choroid, retina, and / or sclera caused by the entry cannula 2900 during use.

[0230] On the other hand, the entry portion 2962 may be tubular and may generally be configured to facilitate the entry and advancement of the injection cannula into the entry cannula 2900. In certain embodiments, the entry portion 2962 is formed from a rigid material including metallic materials such as aluminum, stainless steel, and other metal alloys, or thermoplastic polymer materials such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE). In certain other embodiments, the entry portion 2962 is formed from a flexible material including metallic materials such as nitinol and thermoplastic polymer materials such as polyimide. In certain embodiments, the entry portion 2962 and the spatula portion 2960 may be formed from the same material, and therefore the body 2902 may consist of a single monolithic component. However, in certain other embodiments, the entry portion 2962 and the spatula portion 2960 may be formed from different materials.

[0231] In certain embodiments, the entry portion 2962 optionally includes one or more fixing arms 2970 attached thereto (two fixing arms 2970 are shown in Figure 29A, extending laterally from both sides of the entry portion 2962). One or more fixing arms 2970 may be configured to function as “stops” for fixing the entry cannula 2900 in place after it has been inserted through the sclera and advanced to a desired depth in the suprachoroidal space. Thus, once the entry cannula 2900 has advanced to the desired depth, the fixing arms 2970 may be configured to contact the outer surface of the sclera located outside the incision into which the spatula portion 2960 and part of the entry portion 2962 are inserted, thereby preventing the entry cannula 2900 from advancing any further into the patient’s eye. Therefore, one or more fixing arms 2970 can prevent unintended movement of the entry cannula 2900 after final positioning, thereby reducing the risk of damage to the choroid, retina and / or sclera, and facilitating improved control of the positioning of the injection cannula during subretinal injection. In certain embodiments, one or more fixing arms 2970 may be fixedly coupled to the entry portion 2962. In certain other embodiments, one or more fixing arms 2970 may be extendably coupled to the entry portion 2962, thereby allowing one or more fixing arms 2970 to be actively extended by the user laterally outward from the entry portion 2962 or perpendicular to the main longitudinal axis of the entry cannula 2900 during use. In general, the fixing arms 2970 may have any suitable dimensions and form. In the example of Figure 29A, the fixing arms 2970 are shown as curved or bent wires resembling a "horn" that can extend laterally from the entry portion 2962.

[0232] Figures 29B and 29C show perspective views of the entry cannula 2900 in use. In Figure 29B, the entry cannula 2900 is first inserted through an incision 2994 in the sclera 2992 of the patient's eye 2990. In embodiments including a fixing arm 2970, the entry cannula 2900 is inserted through the incision until one or more fixing arms 2970 contact the sclera 2992. In certain embodiments, the sclera 2992 may be incised using a trocar in combination with the entry cannula 2900. For example, the trocar may be positioned through the distal end of the central channel 2908 of the entry cannula 2900 and extend from there. The portion of the trocar extending from the central channel 2908 is then inserted into the eye 2990, thereby forming an incision until the bottom surfaces of one or more fixing arms 2970 contact the sclera 2992. Subsequently, the trocar can be removed from the eye 2990, leaving the entry cannula 2900 in place.

[0233] Subsequently, as shown in Figure 29C, the injection cannula 2910 of the delivery device can be inserted into and advanced through the entry cannula 2900 until its distal end is positioned adjacent to the target subretinal injection site for injection. By utilizing the entry cannula 2900, the user can microscopically observe the advancement of the injection cannula 2910 through the suprachoroidal space without having to concentrate on its sliding through the scleral incision. This ultimately promotes better control and more efficient placement of the injection cannula 2910, while also reducing the risk of damage to ocular tissue.

[0234] Figures 30A and 30B show perspective views of another exemplary entry cannula 3000 according to a particular embodiment of the present disclosure. Similar to entry cannula 2900, entry cannula 3000 is an exemplary entry cannula that can be used to facilitate the entry of an injection cannula of a delivery device into the suprachoroidal space through the sclera of the eye, as described above with reference to Figure 3. Thus, entry cannula 3000 can be used in combination with, for example, delivery devices 1800 and 1801 in Figures 18A-18B, delivery device 2600 in Figure 26, and other delivery devices for subretinal injection described herein. However, embodiments of entry cannula 3000 can be combined with other delivery devices and / or components described herein, without limitation.

[0235] As shown in the figure, the entry cannula 3000 includes a tubular body 3002 having a central channel 3008 extending from the proximal end 3004 of the body 3002 to the distal end 3006 of the body 3002. After the entry cannula 3000 is inserted through the sclera of the patient's eye, the central channel 3008 functions as an entry point or port for the subsequent insertion of the injection cannula of the delivery device. Therefore, the central channel 3008 may have a transverse dimension along its longitudinal length that is substantially the same as or greater than that of the injection cannula inserted through it.

[0236] In certain embodiments, the main body 3002 includes a distal tubular portion 3060 including a distal end 3006 and a proximal funnel portion 3062 including a proximal end 3004. The distal tubular portion 3060 is substantially tubular and may have an upper cross-section similar to a circular or elliptical shape. As shown in Figures 30A and 30B, the end face 3068 of the tubular portion 3060 may be positioned at a non-perpendicular angle with respect to the main longitudinal axis of the tubular portion 3060, thereby forming a bevel or wedge shape at the distal end 3006. This bevel or wedge shape facilitates choroidal dissection (i.e., separation) as the distal end 3006 of the entry cannula 3000 advances into the suprachoroidal space after passing through the sclera of the patient's eye. In certain embodiments, the tubular portion 3060 is formed from a rigid material including a metallic material such as aluminum, stainless steel, and other metal alloys, or a thermoplastic polymer material such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE). In certain other embodiments, the tubular portion 3060 is formed from a flexible material including a metallic material such as nitinol and a thermoplastic polymer material such as polyimide. By utilizing a flexible material for the tubular portion 3060, the strain on the choroid, retina, and / or sclera during insertion of the entry cannula 3000 can be reduced, thereby reducing damage to the choroid, retina, and / or sclera caused by the entry cannula 3000 during use.

[0237] On the other hand, the funnel portion 3062 can generally be configured and shaped to facilitate the entry and advancement of the infusion cannula into the entry cannula 3000. In certain 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 infusion cannula into the central channel 3008 during use. For example, in the embodiments of Figures 30A and 30B, the funnel portion 3062 includes a semi-funnel-shaped form including a hyperbolic wall 3064 coupled to a planar wall 3066. In such embodiments, the hyperbolic wall 3064 can mechanically direct the infusion cannula into the central channel 3008 as the hyperbolic wall 3064 tapers conically proximal to the central channel 3008. At the same time, the planar wall 3066 can facilitate the positioning of the funnel portion 3062 relative to the outer surface of the sclera of the patient's eye. In other words, the planar wall 3066 is configured to be flat with respect to the outer surface of the eye, thereby improving the stability of the entry cannula 3000 in use and reducing its undesirable movement. In certain embodiments, the planar wall 3066 may also indicate the orientation of the end face 3068 of the tube portion 3060, thereby facilitating easier positioning and orientation of the entry cannula 3000 after it has already been inserted through the sclera. For example, the planar wall 3066 may be positioned on the same or opposing side of the entry cannula 3000 that the end face 3068 faces, so that the user can know the orientation of the end face 3068 simply by looking at the orientation of the planar wall 3066.

[0238] In certain embodiments, the funnel portion 3062 is formed from a rigid material including a metallic material such as aluminum, stainless steel, and other metal alloys, or a thermoplastic polymer material such as polyether ether ketone (PEEK), polyether ketone (PEK), and polytetrafluoroethylene (PTFE). In certain other embodiments, the funnel portion 3062 is formed from a flexible material including a metallic material such as nitinol and a thermoplastic polymer material such as polyimide. In certain embodiments, the funnel portion 3062 and the tube portion 3060 may be formed from the same material, and therefore the body 3002 may consist of a single monolithic component. However, in certain other embodiments, the funnel portion 3062 and the tube portion 3060 may be formed from different materials.

[0239] Figures 31A to 31C show schematic cross-sectional views of exemplary subretinal delivery devices 3100a, 3100b, and 3100c, respectively, according to a particular embodiment of the present disclosure. Delivery devices 3100a to c include a handle having an integrated fluid drive system, which facilitates easier handling of the delivery devices 3100a to c during subretinal injection procedures and reduces the number of components required for such procedures. Delivery devices 3100a to c may be used, for example, as delivery device 414 in the surgical system 400 of Figure 4, and their embodiments may be combined with other delivery devices and / or components described herein, without limitation.

[0240] Now, returning to Figure 31A, the delivery device 3100a includes a handle 3102 and an injection cannula 3110 having a proximal end 3116 coupled to the distal end 3104 of the handle 3102 and extending distally therefrom. The injection cannula 3110 may include any suitable type of injection cannula, including those described elsewhere in this specification. A curved or substantially straight injection needle 3112 is positioned within the injection cannula 3110 to puncture the desired ocular tissue (e.g., the retina or choroid) and deliver fluid into the subretinal space. Similar to the injection cannula 3110, the injection needle 3112 may include any suitable type of injection needle, including those described elsewhere in this specification. In certain embodiments, the injection needle 3112 is configured to slidably extend from the distal end 3114 of the injection cannula 3110 via manual control of a toggle 3140 on the handle 3102 and retract into it. In certain embodiments, the injection needle 3112 is coupled to an internal fluid shaft 3120 that is at least partially located within the cannula 3110. In such embodiments, the internal fluid shaft 3120 may be slidably located within the cannula 3110 to facilitate extension and retraction of the injection needle 3112 when the toggle 3140 is operated.

[0241] To simplify the preparation and delivery of fluids for subretinal injection, a fluid drive system 3160a is integrated into 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 fluid pump) no longer needs to be connected to the delivery device 3100a. Thus, the surgeon can concentrate more attention on the procedure and the delivery device 3100a being used during the procedure without being involved in the setup and operation of the external fluid drive system. This, in turn, improves the efficiency and safety of the subretinal injection procedure. Furthermore, the absence of an external fluid drive system significantly reduces the risk of fluid leakage or other malfunctions during the subretinal injection procedure.

[0242] In Figure 31A, 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 cartridge 3166 configured to be operably coupled to the pistons 3164.

[0243] The drive unit 3162a is configured to generate and apply force or power to the piston 3164, thereby causing the piston 3164 to translate and act on the cartridge 3166, distributing / delivering the injection fluid 3168 contained therein. The drive unit 3162a may generally include any suitable type of electromechanical and / or electromagnetic actuator for axially translating one or more pistons 3164 within the handle 3102. For example, in certain embodiments, the drive unit 3162a includes one or more electromechanical linear or rotary stepper motors. In certain embodiments, the drive unit 3162a includes a rotary feed screw motor, and the piston 3164 includes a threaded slider configured to mesh with the rotary feed screw. When the drive unit 3162a receives a control signal, the drive unit 3162a generates a mechanical rotational or linear force in one or more pistons 3164 operably coupled to it, causing the piston 3164 to axially translate within the handle 3102. In certain embodiments, control signals are provided from a foot controller (e.g., foot pedal 410), a surgical console (e.g., surgical console 402), or other components of the surgical system in the operating environment, which communicate with the delivery device 3100a via wired or wireless communication. To facilitate wireless control of the drive unit 3162a, the delivery device 3100a may further include a wireless communication module 3150, which may include wireless transmitter and receiver circuits for relaying signals (e.g., commands) to and from the delivery device 3100a, in particular the drive unit 3162a. In certain embodiments, the wireless communication module 3150 may communicate wirelessly with the foot controller or surgical console to enable remote control of the drive unit 3162a.

[0244] Cartridge 3166 includes any suitable fluid cartridge having one or more lumens 3170 that at least partially define a volume (e.g., a reservoir) for storing the injection fluid 3168. In certain embodiments, cartridge 3166 includes a replaceable and disposable cartridge pre-filled with the injection fluid 3168 before being inserted into the handle 1802. In such embodiments, cartridge 3166 may include a single lumen 3170 pre-filled with a pre-mixed solution of both a therapeutic solution and a non-therapeutic solution, as described above with reference to Figure 16D. For example, a single lumen 3170 may contain a pre-mixed solution having a desired concentration / ratio of the therapeutic solution (e.g., therapeutic agent) and the non-therapeutic solution. However, in other examples, cartridge 3166 may include two or more lumens 3170 pre-filled with unmixed solutions of the therapeutic solution and / or non-therapeutic solution. In such examples, the therapeutic solution and the non-therapeutic solution can be mixed in cartridge 3166 to a desired concentration / ratio after insertion of cartridge 3166 into the handle and / or during injection.

[0245] The use of pre-filled, replaceable / disposable cartridges 3166 offers surgeons several advantages when performing subretinal injection procedures using the delivery device 3100a. For example, since cartridges 3166 are pre-filled with all the necessary injection fluids, no additional fluid preparation is required before performing a subretinal injection procedure, and the precise concentration / ratio of the components of the delivered injection fluid is guaranteed. Furthermore, such pre-filled cartridges 3166 allow surgeons to immediately determine which therapeutic substance to use for subretinal injection based on the patient's current condition. In addition, since therapeutic substances typically have a shorter shelf life than the delivery device, the separation of cartridges 3166 from the delivery device 3100a allows surgeons to store the delivery device 3100a for longer periods without concern about having to discard the delivery device 3100a due to the expiration of the therapeutic substance.

[0246] However, in yet another embodiment, the cartridge 3166 includes a container fixedly integrated with the handle 3102. In such embodiment, the cartridge 3166 and the handle 3102 may include one or more ports for filling the cartridge 3166 with a therapeutic solution and a non-therapeutic solution before injection.

[0247] As further shown in Figure 31A, in certain embodiments, a movable seal or stopper 3172 is located at the proximal end 3174 of each lumen 3170 of the cartridge 3166 and is operably coupled to one of one or more pistons 3164. Meanwhile, the cartridge 3166 includes a valved port 3178 at the distal end 3176 of each lumen 3170, which is configured to communicate fluidly with the injection cannula 3110, injection needle 3112, and / or internal fluid shaft 3120. During use, the distal axial translation of the piston 3164, driven by the drive unit 3162a, causes the piston 3164 to mechanically engage with the seal 3172, pushing it distally through the lumen 3170, thereby discharging the injection fluid 3168 through the valved port 3178 into the cannula 3110 (and / or internal fluid shaft 3120) and injection needle 3112. In certain embodiments, the force of the injected fluid 3168 against the valved port 3178 causes the valved port 3178 to open, facilitating the flow of the injected fluid 3168 through it. In certain embodiments, the engagement of the cartridge 3166 and the handle 3102 during insertion creates a puncture or opening in the valved port 3178, facilitating the flow of the injected fluid 3168 through it.

[0248] During operation of the delivery device 3100a, the user can activate and control the drive unit 3162a by operating the foot controller, and thus control the movement of the piston 3164. For example, the user can activate the drive unit 3162a by pressing down the foot pedal 410 shown in Figure 4, causing the piston 3164 to translate axially in a forward (e.g., distal) "injection" motion, thereby pushing the injection fluid 3168 out of the cartridge 3166. In certain embodiments, the injection rate (e.g., output flow rate) of the injection fluid 3168 is predetermined and controlled by the drive unit 3162a. In certain embodiments, the user can increase the injection rate by pressing down the foot pedal 410 further to increase the movement of the piston 3164. Alternatively, reducing the pressure on the foot pedal 410 can slow down the movement of the piston 3164 in the injection direction, thereby reducing the injection rate. By not applying pressure to the foot pedal 410, the foot pedal 410 can be moved to a state where it is not fully depressed, thereby completely stopping the movement of the piston 3164 and therefore stopping the injection. In certain embodiments, the speed of movement of the piston 3164, and therefore the injection speed, may correspond linearly to the position of the foot pedal 410.

[0249] In certain embodiments, the user can also control the piston 3164 to move in the reverse direction (e.g., proximal direction), thus enabling the delivery device 3100a to draw fluid into the injection needle 3112 and cannula 3110 (and / or internal fluid shaft 3120). For example, the user may press down a switch on the foot pedal 410 to activate the reverse mode of the delivery device 3100a, and a subsequent press of the foot pedal 410 causes the piston 3164 to actuate in the proximal direction opposite to the injection direction. The reverse mode may include the same mechanism as described above, and the reverse movement speed of the piston 3164 corresponds linearly to the position of the foot pedal 410.

[0250] Now, returning to Figure 31B, the delivery device 3100b is substantially similar to the delivery device 3100a, except for certain aspects of its fluid drive system 3160b. For clarity, only the distinguishing aspects will be described below.

[0251] Instead of drive unit 3162a, the fluid drive system 3160b includes drive unit 3162b. Similar to drive unit 3162a, drive unit 3162b is configured to generate and impart force or power to piston 3164, thereby translating piston 3164 and acting on cartridge 3166 to distribute / deliver the injection fluid 3168 contained therein. However, unlike drive unit 3162a, drive unit 3162b includes an electro-pneumatic driver for axially translating one or more pistons 3164 within handle 3102. Thus, drive unit 3162b can be described as an electro-pneumatic drive unit.

[0252] In the exemplary embodiment shown in Figure 31B, the drive unit 3162b includes an electric actuator 3180, one or more fluid canisters 3184 for storing pressurized fluid, and a valve 3182 positioned above and sealing the opening 3186 of each fluid canister 3184, and operably connected to the electric actuator 3180. Suitable pressurized fluids include, but are not limited to, carbon dioxide, nitrogen, and argon.

[0253] When the drive unit 3162b receives a control signal while the delivery device 3100b is in use, the electric actuator 3180 can open and / or close valves 3182 to control the flow rate of pressurized fluid into pressurized pockets 3188 located between each fluid canister 3184 and the corresponding piston 3164 through openings 3186. In the closed state, each valve 3182 blocks the flow of fluid into the corresponding pressurized pocket 3188. When a valve 3182 is open, pressurized fluid can flow into the pressurized pocket 3188 at a flow rate controlled according to the position of the valve 3182. The accumulation of pressurized gas in the pressurized pocket 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 distribute the injected fluid 3168 from the cartridge 3166. The valves 3182 may include any suitable type of flow control valve operated by an electromechanical, electromagnetic, or electropneumatic actuator 3180. Suitable valves include, but are not limited to, solenoid valves, proportional valves, plug valves, piston valves, and knife valves.

[0254] Now, returning to Figure 31C, the delivery device 3100c is substantially similar to the delivery devices 3100a and 3100b, with the exception of a specific aspect of its fluid drive system 3160c. For clarity, only the distinguishing aspects will be described below.

[0255] 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 and impart force or power to a piston 3164, which in turn causes the piston 3164 to translate and act upon a cartridge 3166, distributing / delivering the injection fluid 3168 contained therein. However, in Figure 31C, the drive unit 3162c includes a spring-actuated mechanism for axially translating one or more pistons 3164 within the handle 3102. Thus, the drive unit 3162c can be described as a spring-actuated drive unit.

[0256] In the exemplary embodiment shown in FIG. 31C, drive unit 3162c includes springs or similar devices 3190 and stop mechanisms or brakes 3192 operably coupled to each of one or more pistons 3164. Each spring 3190 is disposed proximal to the corresponding piston 3164 and provides a constant biasing force in the distal direction with respect to piston 3164. However, simultaneously, stop mechanism 3192 provides a stopping force to piston 3164 to prevent the translation of piston 3164 biased by spring 3190. The stopping force can be provided to piston 3164 as a lateral inward frictional force perpendicular to the major longitudinal axis of handle 3102 (as in FIG. 31C), or the stopping force can be provided in the proximal direction with respect to piston 3164.

[0257] When drive unit 3162c receives a control signal during use of delivery device 3100c, stop mechanism 3192 can controllably release the corresponding piston 3164, thereby allowing spring 3190 to actuate piston 3164 in the distal direction and act on cartridge 3166 to dispense infusion fluid 3168. In certain embodiments, the infusion rate can be controlled by inversely adjusting the amount of stopping force provided to piston 3164 by stop mechanism 3192. For example, by decreasing the amount of stopping force, the flow rate of infusion fluid 3168 from cartridge 3166 can be increased, and by increasing the amount of stopping force, the flow rate of infusion fluid 3168 from cartridge 3166 can be decreased.

[0258] FIGS. 32A - 32D show side schematic views of exemplary support arms 3200a and 3200b for supporting a delivery device during a subretinal infusion procedure, according to certain embodiments described herein. Support arms 3200a and 3200b can be utilized with any of a delivery device and / or delivery system as described herein, without limitation.

[0259] Generally, support arms 3200a and 3200b are configured to support or hold a delivery device during a subretinal injection procedure such that the delivery device need not be held by a surgeon or other surgical staff throughout the procedure. This facilitates improved positioning of the injection needle within the patient's eye and reduces unwanted movement that would occur if the delivery device were held by the user.

[0260] As shown in FIG. 32A, a first support arm 3200a is shown supporting a delivery device 3210 inserted into an eye 3216 of a patient 3212. The first support arm 3200a includes a serial arm having a plurality of articulatable links 3202 coupled by a rotatable joint 3204 that can be locked in a rotational position. The links 3202 can generally include any suitable elongate rigid member, and the rotatable joint 3204 can generally include any suitable type of lockable rotatable joint, including a lockable pin or knuckle joint.

[0261] In the illustrated example, the support arm 3200a includes three links 3202a - 3202c, where link 3202a includes the proximal-most link, link 3202b includes the intermediate link, and link 3202c includes the distal-most link. However, the use of more or fewer links 3202 is further envisioned. For example, the use of more links 3202 (and thus more rotatable joints 3204) can facilitate more articulation points for the support arm 3200a.

[0262] Links 3202a to 3202c are sequentially connected to each other by two rotary joints 3204b and 3204c, with rotary joint 3204b movably connecting the most proximal link 3202a to the intermediate link 3202b, and rotary joint 3204c connecting the intermediate link 3202b to the most distal link 3202c. The most proximal link 3202a is further movably connected to the base 3206 via rotary joint 3204a, while the most distal link 3202c is movably connected to the delivery device adapter 3208 via rotary joint 3204d. Each of the rotary joints 3204a to 3204d is oriented to facilitate the rotation of link 3202 and / or delivery device adapter 3208 about a horizontal axis parallel to the horizontal axis X in Figure 32A. On the other hand, the base 3206 may include a lockable rotary bearing, thereby facilitating rotation of the base 3206 about a vertical axis parallel to the vertical axis Y in Figure 32A. Thus, when the link 3202, rotary joint 3204, and base 3206 are coupled to the delivery device adapter 3208, they fully facilitate at least three degrees of freedom for the delivery device 3210.

[0263] Figure 32B shows an enlarged side schematic view of the delivery device adapter 3208 coupled to the rotary joint 3204d. As shown, the delivery device adapter 3208 includes a holder 3230 movably coupled to the rail 3232. The holder 3230 includes any suitable type of gripping device configured to securely and detachably grip the delivery device 3210 (shown by a dashed line in Figure 32B). In certain examples, the holder 3230 includes a tubular or ring-shaped body through which the delivery device 3210 can be inserted and secured via friction or other locking mechanism. In other examples, the holder 3230 includes a clamp. In yet another example, the holder 3230 includes a clip.

[0264] The holder 3230 is configured to translate (e.g., slide) linearly along the rail 3232 in two opposite directions (represented by arrows 3218a and 3218b), which facilitates the longitudinal movement of the delivery device 3210 parallel to the main longitudinal axis A of the delivery device when the delivery device 3210 is coupled thereto. This one-dimensional translational movement of the holder 3230 can be controlled independently of the rest of the support arm 3200a, thus allowing for fine adjustment of the longitudinal position of the delivery device 3210 when inserted into the eye 3216 of the patient 3212. For example, such translational movement of the holder 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 holder 3230 can be controlled by any suitable mechanism, such as a rotary knob or similar device. In certain embodiments, the holder 3230 can be locked in place after being adjusted to a desired position along the rail 3232 by any suitable releasable locking means.

[0265] Now, returning to Figure 32A, during use, the base 3206 of the support arm 3200a may be rotatably coupled to the operating table 3220 (or other support structure) on which the patient 3212 lies to perform the subretinal injection procedure, around a vertical rotation axis parallel to the Y-axis. Fixing the support arm 3200a to the operating table 3220 facilitates improved stability of the support arm 3200a during the performance of the subretinal injection procedure, thereby minimizing any unintended movement transmitted to (i.e., causing) the delivery device 3210. Thus, the risk of injury to the patient's eye 3216 caused by unintended movement of the delivery device 3210 is reduced, and the skill level required to perform the procedure is eased.

[0266] In certain embodiments, the support arm 3200a is further configured to be movable and stationary on the patient's head 3214 during the subretinal injection procedure. This can provide at least partial inherent compensation for head movement by the patient 3214 during the procedure, as the support arm 3200a will move with the patient's head 3214 and transmit such movement to a delivery device 3210 to which it is detachably coupled. For example, any involuntary movement of the patient's head 3214 caused by the patient's breathing can be essentially transmitted to the support arm 3200a, which then transmits that movement to the delivery device 3210. In Figure 32A, the nearest-position link 3202a is shown stationary on the patient's head 3214. In such an example, the rotational joint 3204a does not have to be locked in place during the subretinal injection procedure, allowing free movement of the link 3202a relative to a base 3206 which can be locked in place around its own axis of rotation. In yet another embodiment, the support arm 3200a may be used when it is not resting on the patient's head 3214. In such an embodiment, the rotary joint 3204a may be locked in a position such that the link 3202a does not come into contact with the patient's head 3214.

[0267] In certain embodiments, each of the links 3202 can be manually adjusted by the surgeon before performing a subretinal injection using the delivery device 3210 in order to manipulate the support arm 3200a to a desired position / orientation. In certain 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, in order to adjust the links 3202, the rotary joint 3204 must first be unlocked, thereby allowing free movement of each of the links 3202. In certain examples, each of the rotary joints 3204 can be released individually to allow movement of only adjacent links 3202. However, in certain other examples, all rotary joints 3204 are released simultaneously via a single mechanism or action to allow movement of all links 3202. The rotary joints 3204 can be released via any suitable mechanical or electronic mechanism. For example, in certain embodiments, the rotary joint 3204 may be mechanically released via a push-push mechanism, push button, locking screw, or other mechanical means located on the support arm 3200a. In certain other embodiments, the rotary joint 3204 may be released via an electromechanical locking mechanism upon user input from a button or switch on the support arm 3200a, a foot pedal, or other user input device. In certain other embodiments, the rotary joint 3204 may be locked in place via the same or similar mechanisms described above for releasing the rotary joint 3204.

[0268] In general, the operation of link 3202 can be achieved before or after inserting the delivery device 3210 into the delivery device adapter 3208 and / or before or after inserting the delivery device 3210 into the patient's eye 3216. For example, in a particular embodiment, 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 link 3202 is operated to maneuver the mounted delivery device 3210 toward the patient's eye 3216 into it. At this point, the rotary joint 3204 is locked in place, and the holder 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 space. The holder 3230 can then be locked in place, and the injection fluid can then be delivered into the subretinal space via the delivery device 3210.

[0269] In certain other embodiments, the delivery device 3210 is first inserted into the patient's eye 3216. The rotary joint 3204 of the support arm 3200a is then released, and the link 3202 is operated to maneuver the delivery device adapter 3208 relative to 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 link 3202 may then be optionally finalized before the rotary joint 3204 is locked. The holder 3230 of the delivery device adapter 3208 is then finely adjusted and locked in place, and the injection fluid is delivered to the subretinal space via the delivery device 3210.

[0270] In certain embodiments, the links 3202 are configured to be freely adjusted manually by the surgeon. In certain embodiments, the links 3202 are configured to be adjusted via one or more knobs 3240 on each link 3202 or rotary joint 3204. In such embodiments, the knobs 3240 may include any suitable mechanical control mechanism for operating the corresponding links 3202, such as push buttons, switches, or rotary knobs. In certain embodiments, the knobs 3240 are operably connected to, for example, one or more gears to control the angle and / or movement of each link 3202 in one or more directions. In further embodiments, instead of physical knobs 3240, the links 3202 may be controlled by digital knobs driven by an electronic controller, such as a controller that communicates with other devices including a surgical console or a computer. For example, the digital knobs may include digital control, such as provided by a computer software interface, which, when adjusted by the surgeon, sends a signal to the electronic controller to drive the operation of the link 3202 (for example, via the rotation of the rotary joint 3204). In such embodiments, the support arm 3200a may be a fully or partially robotic arm. In this embodiment, the support arm 3200 may be controlled via a joystick rather than via a software interface.

[0271] As described above, Figures 32C and 32D show schematic side views of another exemplary support arm 3200b. Support arm 3200b is substantially similar to support arm 3200a in terms of structure and function, but differs in several aspects as described below.

[0272] As shown in Figures 32C and 32D, the support arm 3200b is movably coupled to the patient 3212's head 3214 via a band 3260 configured to be worn by the patient 3212. The fixation of the support arm 3200b to the patient 3212's head 3214 provides complete compensation for any head movement by the patient 3212 during the procedure, as the support arm 3200b moves / rotates with the patient's head 3214 and transmits such movement to a delivery device 3210 to which it is detachably coupled. Thus, any involuntary movement of the patient's head 3214 caused by the patient's breathing can be transmitted directly to the support arm 3200b, which then transmits that movement to the delivery device 3210. In Figure 32C, the band 3260 includes a headband configured to be fixed around the forehead and crown of the patient 3212's head 3214. In Figure 32D, the band 3260 is configured to be secured around the chin and upper part of the head 3214 of the patient 3212.

[0273] In Figures 32C and 32D, the support arm 3200ba is coupled to the band 3260 via a base 3206 rotatably attached to the band 3260. Furthermore, the support arm 3200b includes only two links 3202, namely the most proximal link 3202d and the most distal link 3202e, which are movably coupled together via a rotary joint 3204e. In these two examples, the support arm 3200b may not require as many links 3202 as an independent support arm such as the support arm 3200a, which is configured to support the patient 3212 away from the head 3214. However, even with fewer links 3202, the support arm 3200b may function substantially the same as the support arm 3200a. Furthermore, the use of more or fewer links 3202 for the support arm 3200b is further conceivable.

[0274] Figure 33A shows an exemplary operating environment 3300, such as an ophthalmic operating environment during the performance of a subretinal injection procedure according to a particular embodiment of the present disclosure. As described above, subretinal injection procedures are typically very delicate procedures because they require the puncture and / or manipulation of one or more tissues / membranes of the eye to access the subretinal space. Thus, such procedures require considerable skill from the surgeon 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 and volume of fluid delivered into the subretinal space. Delivery of too much fluid and / or too quickly can cause undesirable trauma to the tissues on both sides of the subretinal space (e.g., the retina and RPE). On the other hand, delivery of too little fluid (e.g., too little therapeutic agent) can reduce the effectiveness of the procedure. Thus, control of the volume and flow of fluid delivered is crucial to the success of a subretinal injection procedure. The following description provides systems and methods for improving the control of the volume and flow of fluid delivered during subretinal injection. Such systems and methods may be used in combination with delivery systems and delivery devices described in any part of this specification, but are not limited to these.

[0275] As shown in Figure 33A, the operating environment 3300 includes a surgical system 3302 which may represent a surgeon 3310, a patient 3312, and the surgical system 400 described above with reference to Figure 4. Thus, the surgical system 3302 includes various systems and tools such as a surgical console 3320, a display device 3322, a microscope system 3324, a foot pedal 3326, and a delivery device 3328 which may include any of the delivery devices and / or delivery systems described herein. In certain embodiments, the surgical system 3302 further includes a fluid drive system 3330 which is configured to drive the flow of the injection fluid into the subretinal injection fluid and may be located, for example, within the 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.

[0276] The surgical console 3320 also includes a controller 3304 (shown by a dashed line), and in certain embodiments, includes a receiver 3306 that communicates with the controller 3304. The controller 3304 is configured to cause the surgical console 3320 to perform (e.g., control) one or more tasks for driving a subretinal injection procedure, such as driving the flow of injection fluid via the fluid drive system 3330, according to input from the surgeon 3310 and / or the type of procedure, and stored settings and parameters related to the surgeon 3310 and / or the patient 3312. In certain 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.

[0277] The receiver 3306 may include any suitable interface for communication (e.g., one-way or two-way signals) between the controller 3304 and, for example, the foot pedal 3326 and / or the delivery device 3328. For example, the receiver 3306 may include a wireless or wired connection between the controller 3304 and the foot pedal 3326 and / or the delivery device 3328. In certain embodiments, the receiver 3306 also communicates with a microphone 3332 configured to receive voice commands from the surgeon 3310 and / or other surgical staff and convert them into signals that are processed and utilized by the controller 3304 to perform one or more tasks for driving a subretinal injection procedure. Although shown on the surgical console 3320, the microphone 3332 may be located at any suitable location within the operating environment 3300.

[0278] In the embodiment of Figure 33A, the controller 3304 and receiver 3306 are integrated into the surgical console 3320, in which case the controller 3304 includes or refers to one or more processors and / or memory devices integrated into the surgical console. In certain other embodiments, the controller 3304 and / or receiver 3306 are, for example, standalone devices or modules that communicate wirelessly or via wired connections with the surgical console 3320 and other devices in the operating environment 3300. In certain embodiments, the controller 3304 means a set of software instructions configured to be executed by the processor associated with the surgical console 3320. In certain aspects, the operation of the controller 3304 may be partially performed in a public or private cloud by the processor associated with the controller 3304 and / or the surgical console 3320.

[0279] During subretinal injection procedures, the controller 3304 interfaces (for example, wirelessly or wired) with a foot pedal 3326, a delivery device 3328, and / or a fluid drive system 3330 to control various parameters related to 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 related to the flow of the injected fluid into and out of the patient's eye 3312 during subretinal injection procedures. The fluid flow parameters may be measured directly by the fluid drive system 3330 or a fluid flow sensor or other type of sensor separate from the fluid drive system and then provided to the controller 3304. For example, in embodiments in which 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 traveled in translation with respect to time or the position of the plunger in time, and such information can be processed by the controller 3304 to determine various fluid flow parameters.

[0280] In certain embodiments, the controller 3304 controls fluid flow parameters according to stored settings associated with the treatment type, surgeon 3310, and / or patient 3312. For example, in some embodiments, prior to a subretinal injection procedure, the surgeon 3310 can program the controller 3304 with one or more injection sequences for the particular subretinal injection procedure to be performed and / or for the particular patient 3312. Such an injection sequence can be initiated during the subretinal injection procedure and can include a temporal sequence of desired fluid flow parameters. Generally, the injection sequence can include static settings of fluid flow parameters such as a constant flow rate and / or a constant fluid pressure, or dynamic settings of fluid flow parameters such as a flow rate that changes in relation to time and / or a fluid pressure that changes. The use of a programmed injection sequence having a predetermined temporal sequence of desired fluid flow parameters facilitates accurate and precise (i.e., repeatable) performance of the subretinal injection procedure by the surgeon 3310. Each subretinal injection procedure can also be performed according to the particular needs of the surgeon 3310 and / or patient 3312, thereby improving the efficiency and effectiveness of each procedure. Further, such an injection sequence improves volume and pressure control when injecting fluid into the subretinal space, thereby reducing the risk of damage to the retina and RPE.

[0281] In certain embodiments, the programmed injection sequence defines various settings related to the fluid flow parameters. Such settings include maximum and / or minimum injection fluid flow rates, maximum and / or minimum injection fluid volumes, maximum and / or minimum injection times, maximum and / or minimum injection fluid pressures, maximum and / or minimum rates of change between fluid flow rate, injection fluid volume, and injection fluid pressure, number of injection phases, time and / or order, and the like.

[0282] In certain 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 staff) via inputs received from the surgeon 3310 (and / or other surgical staff) via the foot pedal 3326, delivery device 3328, and / or microphone 3332. For example, in such embodiments, inputs may include manual control operations by the surgeon 3310, such as buttons or other toggles on the delivery device 3328, and / or foot-operated control operations, such as pedals on the foot pedal 3326. In certain examples, inputs may include voice commands received from the surgeon 3310 via the microphone 3332. The use of voice commands for fluid flow control may facilitate easier handling of the delivery device 3328 and / or other surgical tools during subretinal procedures, as it does not require additional motor coordination by the surgeon 3310 to adjust or control fluid flow parameters. Therefore, the surgeon 3310 can concentrate all their attention on keeping the delivery device 3328 stationary during injection.

[0283] Signals corresponding to inputs on the delivery device 3328, foot pedal 3326, and / or microphone 3332 are received by the receiver 3306 and communicated to the controller 3304, which then takes one or more actions to control the fluid drive by the fluid drive system 3330 according to inputs from the surgeon 3310 (and / or other surgical staff) and programmed injection sequences. In certain embodiments, inputs from the surgeon 3310 are mapped by the controller 3304 to corresponding injection sequences, fluid flow parameters, and / or operations to be performed by the fluid drive system 3330 and / or surgical console 3320, and the controller 3304 then configures and drives the fluid drive system 3330 and / or surgical console 3320 to perform such injection sequences, fluid flow parameters, and / or operations. In certain embodiments, the injection sequences, fluid flow parameters, and / or actions being performed or to be performed are displayed on the display device 3322 for the surgeon 3310.

[0284] In certain embodiments, the programmed injection sequence includes a user-programmed (e.g., surgeon-programmed) injection sequence programmed before the subretinal injection procedure is performed. In certain embodiments, in addition to or as an alternative to the injection sequence programmed by surgeon 3310, the controller may include one or more pre-programmed general-purpose injection sequences and / or other settings associated with the subretinal injection procedure. Such pre-programmed general-purpose 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 the surgical system 3302 during manufacturing or assembly. In such embodiments, input from surgeon 3310 during the procedure is mapped by controller 3304 to a corresponding pre-programmed general-purpose injection sequence and / or other settings to be performed by the fluid-driven system 3330 and / or surgical console 3320, and the controller 3304 then configures and drives the fluid-driven system 3330 and / or surgical console 3320 to perform according to such pre-programmed general-purpose injection sequences and / or other settings.

[0285] In certain embodiments utilizing programmed or pre-programmed infusion sequences, the controller 3304 includes a safety device for stopping the flow of infusion fluid driven by the fluid drive system 3330 during the initiated infusion sequence. For example, in certain embodiments, the controller 3304 may be programmed to require continuous manual input from the surgeon 3310 to continue or perform the initiated infusion sequence. In other words, the controller 3304 may include a “dead man switch” that stops the performance of the infusion procedure if there is no input from the surgeon 3310. Continuous manual input may include continuous operation of one or more foot-operated controls on the foot pedal 3326 and / or continuous operation of one or more hand-operated controls on the delivery device 3328. For example, in order for the infusion sequence to be started and performed to completion, the surgeon 3310 may be required to press down the pedal on the foot pedal 3326 throughout the entire infusion sequence. Thus, if any problem occurs during the infusion sequence, the surgeon 3310 can release the pedal to immediately stop the infusion sequence. In such an example, by using the foot pedal 3326 as a dead man's switch rather than another device within the operating environment 3300, unnecessary visual distraction of the surgeon 3310 during the injection procedure can be reduced, allowing the surgeon 3310 to concentrate more visual attention on the patient's 3312 eye and the operation of the delivery device 3328 within it.

[0286] In further embodiments, the controller 3304 can control fluid flow parameters entirely or partially based on real-time input from the surgeon 3310 (and / or other surgical staff), thus enabling complete manual control of the subretinal injection procedure. Similarly, as described above, the input may include the operation of a hand-operated control on the delivery device 3328 and / or a foot-operated control on the foot pedal 3326 by the surgeon 3310. In such an example, the degree or level of operation of the hand or foot-operated control (e.g., the degree or amount of pressing down) may correspond to the magnitude of the fluid flow parameters. For example, further pressing down on the hand or foot-operated control may result in an increase in fluid flow rate, fluid pressure and / or fluid delivery volume, while reducing (or releasing) the pressing of the hand or foot-operated control may result in a decrease in fluid flow rate, fluid pressure and / or fluid delivery volume. In certain examples, the input may include voice commands received from the surgeon 3310 via the microphone 3332.

[0287] Signals corresponding to inputs on the delivery device 3328, foot pedal 3326, and / or microphone 3332 are received by the receiver 3306 and communicated to the controller 3304, which then takes one or more actions to drive the fluid drive system 3330 according to input from the surgeon 3310 (and / or other surgical staff).

[0288] In certain embodiments, during the execution of a subretinal injection procedure, the surgical system 3302 may provide visual and / or auditory feedback to the surgeon 3310 and / or other surgical staff regarding fluid flow parameters and the progress of the procedure. For example, in certain embodiments, measured values ​​of fluid flow parameters (as volume units (e.g., μL (microliters)) or as a percentage of volume (e.g., %)) and / or the status or progress of the injection sequence may be continuously or periodically displayed on the screen of the display device 3322 and / or on the screen or eyepiece of the microscope system 3324. In certain embodiments, the surgical system 3302 may include a speaker 3334 for providing the surgeon 3310 with periodic audible indicators regarding fluid flow parameters and / or the progress of the procedure. In such embodiments, the audible indicators may facilitate easier handling of the delivery device 3328 and / or other surgical tools during the subretinal procedure, as the number of visual distractions during the procedure is reduced or limited. Therefore, the surgeon 3310 can concentrate their full visual attention on keeping the delivery device 3328 stationary during injection. Examples of suitable audible indicators include both verbal and non-verbal sounds. Where non-verbal sounds are used, the type, frequency, amount, or tone of the non-verbal sound can indicate different parameters and / or status of the subretinal injection procedure. In certain embodiments, the audible indicator may be provided periodically at predetermined intervals based on the time or volume of the fluid being injected. Such an audible indicator may indicate a measurement of the fluid flow parameter as a volume unit (e.g., μL) or as a percentage of volume (e.g., %).

[0289] Figure 33B shows an exemplary diagram illustrating how the various components of the operating environment 3300 shown in Figure 33A operate, communicate, and work together. As illustrated, the surgical console 3320 of the surgical system 3302 includes, but is not limited to, a controller 3304 and a receiver 3306 that enables the controller 3304 to be connected 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, memory 3368, and storage 3370. The CPU 3366 can retrieve application data and store it in memory 3368, and can retrieve and execute instructions stored in 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, network interface 3362, memory 3368, storage 3370, delivery device 3328, and fluid drive system 3330. The CPU 3366 can represent a single CPU, multiple CPUs, a single CPU with multiple processing cores, etc. The memory 3368 represents random access memory.

[0290] Storage 3370 may be a disk drive. Although shown as a single unit, storage 3370 may be a combination of fixed or removable storage devices, such as a fixed disk drive, removable memory card or optical storage, network-attached storage (NAS) or storage area network (SAN). Storage 3370 may include user-programmed subretinal injection procedure parameters / settings 3372, such as a user-programmed injection sequence 3374. Storage 3370 may further include pre-programmed subretinal injection procedure parameters / settings 3376, such as a pre-programmed general-purpose injection sequence 3378. Each of the user-programmed injection sequence 3374 and the pre-programmed general-purpose injection sequence 3378 may include pre-set instructions for controlling fluid flow parameters driven by the fluid drive system 3330.

[0291] On the other hand, memory 3368 includes an operating system 3380 and / or one or more applications, which, when executed by CPU 3366, allow controller 3304 to configure and operate the surgical console 3320 (including, for example, a fluid drive system 3330 based on acquired subretinal injection procedure parameters / settings).

[0292] Figures 34A–34D show partial cross-sectional views of an eye 3400 in different steps of performing an exemplary subretinal injection procedure with post-injection sealing according to a particular embodiment of the present disclosure. During and after the injection of fluid into the subretinal space at the target injection site, some leakage or outflow of non-therapeutic and / or therapeutic solutions through the target injection site may occur. This is typically undesirable because leakage of any therapeutic material can reduce the effectiveness of the procedure and also increase the risk of undesirable complications arising from contact between the therapeutic material and non-target ocular tissue. Therefore, as described elsewhere in this specification, once the fluid has been 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 from the subretinal space. The following description includes an example of performing such sealing after subretinal delivery of the fluid using a transvitreous method. A suprachoroidal method is described, but embodiments of the following method may be applied using the suprachoroidal method.

[0293] Returning to Figure 34A, transvitreous subretinal injection is performed using any suitable delivery device and / or system described herein. For example, the injection cannula 3510 of a delivery device may be inserted through a valved insertion cannula (or other entry cannula) positioned through a scleral incision in the eye 3400 and 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 adjacent to the target injection site 3406 on the surface of the retina 3404. Once in position, the injection needle 3512 of the delivery device may be extended and / or inserted through the target injection site 3406 into the subretinal space 3424, for example, between the outermost nerve layer of the retina 3404 and the retinal pigment epithelium (RPE) 3408, and the fluid 3418 may be injected into the subretinal space 3424. Subsequently, the injection needle 3512 can be retracted into the cannula 3510, and the cannula 3510 can be removed from the eye 3400 through the valved insertion cannula.

[0294] At this point, the target injection site 3406 can be sealed using one of several sealing modalities. Figures 34B to 34D show various sealing modalities that can be used in combination with subretinal injection procedures.

[0295] As shown in Figure 34B, in certain embodiments, the graft 3440 is applied to cover the target injection site 3406 using a suitable applicator device such as forceps 3442. For example, the graft 3440 can be grasped and inserted into the eye 3400 using forceps 3442 (e.g., through a valved cannula or another intrascleral entry cannula), and then positioned and flattened over the target injection site 3406 so that the graft 3440 seals the target injection site 3406.

[0296] In certain embodiments, the graft 3440 includes a biological graft or scaffold, such as a cell graft. In certain embodiments, the graft 3440 includes a human amniotic membrane (hAM) graft. The amniotic membrane or amnion is the innermost layer of the placenta and consists of a non-adhesive basement membrane, a thick intermediate collagen layer, and an adhesive avascular stromal matrix. For sealing purposes, the adhesive stromal matrix of the amnion may be placed "face down" on the surface of the retina 3404 so as to adhere to the retina 3404 and seal the target injection site 3406. Other examples of biological scaffolds or cell grafts that can be used include scaffolds or grafts containing retinal cells, such as iPSC-derived retinal cells.

[0297] In certain embodiments, the graft 3440 includes a polymer-based scaffold, such as a polymer nanofiber scaffold.

[0298] Now, returning to Figure 34C, as an alternative to a graft, the sealing solution 3450 may be applied to cover the target injection site 3406 using a suitable applicator device such as an injector 3452. In certain embodiments, the sealing solution 3450 may contain one or more human proteins and / or cell adhesion factors in a solution that can be injected into the target injection site 3406 to seal the target injection site 3406. Examples of proteins and adhesion factors that may be utilized 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 may be spontaneously degraded in vivo by the patient's own catabolic pathways / processes.

[0299] In certain embodiments, the encapsulation solution 3450 contains polymers that can be spontaneously degraded in vivo by the patient's own catabolic pathways / processes. For example, in certain embodiments, the encapsulation solution 3450 may contain polymer hydrogels such as biopolymers. Examples of biopolymers that can be used include chitosan, hyaluronic acid, gelatin, alginate, methylcellulose, and collagen.

[0300] Figure 34D shows yet another alternative sealing modality. In Figure 34D, the target injection site 3406 within the retina 3404 is sealed via photocoagulation by a laser probe 3460. Thus, the laser probe 3460 may include any suitable type of retinal treatment laser probe operably coupled to a laser source for generating and propagating a laser beam having a wavelength of approximately 400 to approximately 850 nm. For example, the laser probe 3460 can be operably coupled to an Nd-YAG laser source. Thus, using the laser probe 3460, a laser beam 3462 can be directed to the target injection site 3406, which can cauterize and seal the retina 3404 at the target injection site 3406, thereby preventing the previously delivered therapeutic material from escaping.

[0301] In summary, embodiments of the present disclosure improve the efficacy, efficiency, and safety of subretinal injections for the treatment of ocular conditions.

[0302] As used herein, the phrase “at least one of” a list of items refers to any combination of those items that include a single member. For example, “at least one of a, b or c” includes a, b, c, ab, ac, bc and abc and any combination of multiple identical elements (e.g., aa, aaa, aab, aac, abb, acc, bb, bbb, bbc, cc and ccc or any other order of a, b and c).

[0303] The above description is provided to enable those skilled in the art to implement the various embodiments described herein. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments. Accordingly, the claims are not intended to be limited to the embodiments shown herein, but rather should be given the entire scope consistent with the language of the claims.

[0304] In the claims, references to singular elements mean "one or more" and not "one and only" unless explicitly stated otherwise. Unless otherwise stated, the term "several" refers to one or more. All structural and functional equivalents of the various embodiments of the elements described throughout this disclosure, known to those skilled in the art or to be known thereafter, are expressly incorporated herein by reference and are encompassed by the claims. Furthermore, nothing disclosed herein is intended to be made public, whether such disclosure is expressly stated in the claims or not. No element of a claim should be construed under Section 112(f) of the United States Patent Act unless it is expressly described using the phrase "means for" or, in the case of a method claim, using the phrase "step for". The word "exemplary" is used herein to mean "to serve as an example, case, or illustration." No embodiment described herein as "exemplary" should be construed as necessarily preferable or advantageous to any other embodiment.

[0305] Exemplary Embodiments Embodiment 1: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and an operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough; and a needle movably disposed within the second lumen and coupled to an operable toggle, configured to extend from the second lumen at the distal end of the cannula and retract into the second lumen when the toggle is activated.

[0306] Embodiment 2: The surgical instrument according to Embodiment 1, wherein the needle comprises a curved needle, the curvature of the needle increases as it is extended from the second lumen, and the curvature of the needle decreases as it is retracted into the second lumen.

[0307] Embodiment 3: The surgical instrument according to Embodiment 2, wherein the needle is formed of an elastic material.

[0308] Embodiment 4: The surgical instrument according to Embodiment 1, further comprising an annular insert positioned in a second lumen at the distal end of a cannula, the annular insert surrounding at least a portion of a needle in the second lumen, wherein extension of the needle from and through the second lumen increases the flexibility of the needle, and retraction of the needle into and through the annular insert increases the rigidity of the needle.

[0309] Embodiment 5: The surgical instrument according to Embodiment 1, wherein the needle comprises a first proximal portion having a first outer diameter and a second distal portion having a second outer diameter.

[0310] Embodiment 6: The surgical instrument according to Embodiment 5, wherein the first proximal portion has a gauge of 38 or less, and the second distal portion has a gauge of 37 or more.

[0311] Embodiment 7: The surgical instrument according to Embodiment 5, wherein the first proximal portion has a gauge of 41 or less, and the second distal portion has a gauge of 40 or more.

[0312] Embodiment 8: The surgical instrument according to Embodiment 1, wherein the needle includes an inclined distal tip, the inclined distal tip including a distal end face positioned at a non-perpendicular and non-zero angle with respect to the principal longitudinal axis of the needle.

[0313] Embodiment 9: The surgical instrument according to Embodiment 8, wherein the needle further includes a port located on its side wall and adjacent to its inclined distal tip.

[0314] Embodiment 10: The surgical instrument according to Embodiment 1, wherein the needle includes an annular sealing element that surrounds a portion of the needle at its distal end.

[0315] Embodiment 11: The surgical instrument according to Embodiment 1, wherein the needle includes a polymer coating formed on its inner wall to reduce fluid resistance through the cannula.

[0316] Embodiment 12: The surgical instrument according to Embodiment 11, wherein the polymer coating is further disposed on the inner wall of the cannula.

[0317] Embodiment 13: The surgical instrument according to Embodiment 11, wherein the polymer coating comprises at least one of poly(ethylene oxide) (PEO), poly(methyl methacrylate) (PMMA), poly(hydroxyethyl methacrylate) (PHEMA), polytetrafluoroethylene (PTFE), ethylenetetrafluoroethylene (ETFE), perfluoroalkoxy (PFA), chlorotrifluoroethylene (E-CTFE), or polyether ether ketone (PEEK).

[0318] Embodiment 14: The surgical instrument according to Embodiment 1, wherein the operable toggle is lockable so that the needle can be fixed in either the extended or retracted position.

[0319] Embodiment 15: The surgical instrument according to Embodiment 1, further comprising a first flexible conduit, the distal end of which is fluid-coupled to an operable toggle or needle in a first lumen, the first flexible conduit being further fluid-coupled to a connector located at the proximal end of a handpiece, the proximal end of which is further configured to fluid-couple to a second flexible conduit outside the first lumen.

[0320] Embodiment 16: The surgical instrument according to Embodiment 15, further comprising a second flexible conduit fluidly coupled to an external connector of the first lumen.

[0321] Embodiment 17: The surgical instrument according to Embodiment 1, wherein an operable toggle is positioned around the handpiece.

[0322] Embodiment 18: The surgical instrument according to Embodiment 1, wherein the operable toggle includes a plurality of toggles surrounding a portion of the handpiece.

[0323] Embodiment 19: The surgical instrument according to Embodiment 1, wherein the handpiece is configured to removably house a cartridge pre-filled with an injection fluid, the cartridge fluidly coupling with a cannula or needle for the injection of the injection fluid.

[0324] Embodiment 20: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and an operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough; and a needle movably disposed within the second lumen and coupled to an operable toggle, configured to extend from the second lumen at the distal end of the cannula and retract into the second lumen when the toggle is activated.

[0325] Embodiment 21: The surgical instrument according to Embodiment 20, wherein at least a portion of the cannula is formed from a flexible metal or thermoplastic material.

[0326] Embodiment 22: The surgical instrument according to Embodiment 21, wherein another portion of the cannula is formed from a rigid material.

[0327] Embodiment 23: The surgical instrument according to Embodiment 20, wherein the cannula includes an elliptical, tablet-shaped, or crescent-shaped cross-sectional profile.

[0328] Embodiment 24: The surgical instrument according to Embodiment 20, wherein the cannula includes a pre-formed curve along the length of the cannula.

[0329] Embodiment 25: The surgical instrument according to Embodiment 20, wherein the cannula further includes a distal tip, the distal tip having a semicircular and disc-shaped distal portion for dissecting tissue when inserted into the eye.

[0330] Embodiment 26: The surgical instrument according to Embodiment 25, wherein the distal tip further includes a proximal portion having a port, and through the port, the needle can be extended from and retracted into a second lumen.

[0331] Embodiment 27: The surgical instrument according to Embodiment 26, wherein the proximal portion of the distal tip further includes an inclined surface positioned adjacent to the port, and the needle is configured to slide along the inclined surface as it is extended and retracted through the port.

[0332] Embodiment 28: The surgical instrument according to Embodiment 20, wherein the cannula further comprises a distal tip formed of a photoluminescent material.

[0333] Embodiment 29: The surgical instrument according to Embodiment 28, wherein the cannula further comprises a distal tip formed of a phosphorescent material.

[0334] Embodiment 30: The surgical instrument according to Embodiment 20, wherein the cannula further includes a distal tip comprising a spatula portion and a body portion, the thickness of the distal tip increasing between the spatula portion and the body portion to form a bevel for dissecting tissue when inserted into the eye.

[0335] Embodiment 31: The surgical instrument according to Embodiment 30, wherein the main body portion includes a port through which a needle can be extended from and retracted into a second lumen.

[0336] Embodiment 32: The surgical instrument according to Embodiment 31, wherein the distal tip body portion further includes an inclined surface positioned adjacent to the port, and the needle is configured to slide along the inclined surface as it extends and retracts through the port.

[0337] Embodiment 33: The surgical instrument according to Embodiment 20, further comprising an optical fiber extending along a cannula and having a terminal portion at or near the distal end of the cannula, wherein the optical fiber is configured to emit light from its terminal portion.

[0338] Embodiment 34: The surgical instrument according to Embodiment 33, wherein the optical propagation fiber includes a single-core or multi-core optical fiber configured to propagate white light.

[0339] Embodiment 35: The surgical instrument according to Embodiment 20, wherein the cannula further includes a distal tip, the distal tip including a port into which a needle can extend from and retract into a second lumen, the port being positioned adjacent to an inclined surface for guiding the needle through the port when the needle extends from and retracts into the second lumen.

[0340] Embodiment 36: The surgical instrument according to Embodiment 35, wherein the proximal end of the needle is coupled to a sliding block, and the sliding block is configured to slide along an inclined surface as the needle extends and retracts through the port.

[0341] Embodiment 37: The surgical instrument according to Embodiment 36, wherein at least one of the sliding block and the inclined surface is formed from a material comprising at least one of steel, titanium, PEEK (polyetheretherketone), polyoxymethylene (POM), and polytetrafluoroethylene (PTFE).

[0342] Embodiment 38: The surgical instrument according to Embodiment 20, wherein the cannula further includes a port, the needle being able to extend from and retract into the second lumen through the port, the port being located within the side wall of the cannula, and the distal portion of the needle having a corkscrew shape to allow extension and retraction of the needle through the port in response to rotation of the needle.

[0343] Embodiment 39: The surgical instrument according to Embodiment 38, wherein the needle is curled along a plane perpendicular to the main longitudinal axis of the needle to form a corkscrew shape.

[0344] Embodiment 40: The surgical instrument according to Embodiment 20, wherein the cannula further includes a distal tip, the distal tip having a first port located on the side wall of the distal tip, the needle being able to extend from and retract into the second lumen through the first port, the port being located adjacent to an inclined surface for guiding the needle through the port when the needle extends from and retracts into the second lumen, and the port being located on the distal surface for injecting fluid along a flow path parallel or substantially parallel to the main longitudinal axis of the distal tip.

[0345] Embodiment 41: The surgical instrument according to Embodiment 40, wherein the second port is fluidly coupled to a fluid conduit located within the cannula.

[0346] Embodiment 42: The surgical instrument according to Embodiment 20, wherein the cannula further comprises 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 located at the distal end of the cannula or on the side wall of the cannula.

[0347] Embodiment 43: The surgical instrument according to Embodiment 42, wherein the wire is configured to increase the rigidity of the cannula for insertion into the eye.

[0348] Embodiment 44: The surgical instrument according to Embodiment 42, wherein the wire is configured to facilitate the guidance of the cannula to the target injection site when inserted into the eye.

[0349] Embodiment 45: A support system for a fluid injection device, comprising a support arm, the support arm comprising a base configured to rotate about its axis, a plurality of articulated links movably coupled to the base, a device adapter movably coupled to at least one link of the plurality of articulated links and configured to fix a fluid injection device, and a plurality of rotary joints movably coupled at least one link of the plurality of articulated links to the device adapter, and adjacent links of the plurality of articulated links and at least one other link of the plurality of articulated links to the base.

[0350] Embodiment 46: The surgical instrument according to Embodiment 45, wherein the base is rotatably coupled to a band configured to be positioned around the patient's head.

[0351] Embodiment 47: The surgical instrument according to Embodiment 45, wherein the base is rotatably coupled to an operating table or other support structure configured to support the head of a patient.

[0352] Embodiment 48: The surgical instrument according to Embodiment 47, wherein the base is configured to rotate about a vertical axis, and at least one of the multiple rotary joints is configured to rotate about a horizontal axis perpendicular to the vertical axis.

[0353] Embodiment 49: The surgical instrument according to Embodiment 47, wherein at least one link of a plurality of articulated links is configured to be positioned relative to the patient's head during use.

[0354] Embodiment 50: The surgical instrument according to Embodiment 45, wherein the multiple articulated links include a series of articulated links.

[0355] Embodiment 51: The surgical instrument according to Embodiment 45, wherein the support arm provides at least three degrees of freedom to the fluid injection device.

[0356] Embodiment 52: The surgical instrument according to Embodiment 45, wherein at least one of the multiple rotary joints is lockable in the rotational direction.

[0357] Embodiment 53: The surgical instrument according to Embodiment 45, wherein the base is lockable in the rotational direction.

[0358] Embodiment 54: The surgical instrument according to Embodiment 45, wherein the device adapter includes a fluid injection device holder movably coupled to a rail.

[0359] Embodiment 55: The surgical instrument according to Embodiment 54, wherein the fluid injection device holder includes a clamp or clip for securing the fluid injection device.

[0360] Embodiment 56: The surgical instrument according to Embodiment 54, wherein the fluid injection device holder includes a tubular or ring-shaped body for securing the fluid injection device.

[0361] Embodiment 57: The surgical instrument according to Embodiment 54, wherein the fluid injection device holder includes a tubular or ring-shaped body for securing the fluid injection device.

[0362] Embodiment 58: The surgical instrument according to Embodiment 54, wherein the fluid injection device holder is configured to translate linearly along a rail, thereby facilitating both rotational and translational motion of the fluid injection device when coupled to a device adapter.

[0363] Embodiment 59: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and at least one operable toggle movably coupled to a handle; an articulated cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough, and configured to articulate when at least one operable toggle is activated; and a needle movably disposed within the second lumen and coupled to at least one operable toggle, configured to extend from the second lumen at the distal end of the cannula and retract into the second lumen when at least one operable toggle is activated.

[0364] Embodiment 60: The surgical instrument according to Embodiment 59, wherein the articulated cannula includes one or more features etched or cut into the outer surface of the articulated cannula to facilitate articulation.

[0365] Embodiment 61: The surgical instrument according to Embodiment 60, wherein the articulated cannula is formed of at least one of aluminum, stainless steel, polyether ether ketone (PEEK), polyether ketone (PEK), or polytetrafluoroethylene (PTFE).

[0366] Embodiment 62: The surgical instrument according to Embodiment 59, further comprising one or more wires coupled at one end to at least one operable toggle and at the other end to one or more points along the length of an articulated cannula in a second lumen, wherein the operation of at least one operable toggle causes the wires to act on the articulated cannula and manipulate the curvature of the articulated cannula.

[0367] Embodiment 63: The surgical instrument according to Embodiment 59, wherein at least one operable toggle includes a first toggle for extending and retracting a needle from a second lumen and a second toggle for operating an articulated cannula.

[0368] Embodiment 64: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and at least one operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough; a reinforcing sleeve disposed around the cannula and configured to translate along the length of the cannula when at least one operable toggle is activated, wherein distal translation of the reinforcing sleeve increases the rigidity of the cannula and proximal translation of the reinforcing sleeve decreases the rigidity of the cannula; and a needle movably disposed within the second lumen and coupled to at least one operable toggle, wherein when at least one operable toggle is activated, the needle extends from the second lumen at the distal end of the cannula and retracts into the second lumen.

[0369] Embodiment 65: The surgical instrument according to Embodiment 64, wherein the reinforcing sleeve includes a hollow tubular body.

[0370] Embodiment 66: The surgical instrument according to Embodiment 65, wherein the reinforcing sleeve is formed of a metallic material including at least one of stainless steel, aluminum, or titanium.

[0371] Embodiment 67: The surgical instrument according to Embodiment 65, wherein the reinforcing sleeve is formed of a composite material comprising at least one of polyetheretherketone (PEEK), polyetherketone (PEK), polytetrafluoroethylene (PTFE), or polycarbonate (PC).

[0372] Embodiment 68: The surgical instrument according to Embodiment 64, wherein the position of the reinforcing sleeve along the length of the cannula is releasably lockable.

[0373] Embodiment 69: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and at least one operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough; a reinforcing sleeve disposed within the cannula and configured to translate along the length of the cannula when at least one operable toggle is activated, wherein distal translation of the reinforcing sleeve increases the rigidity of the cannula and proximal translation of the reinforcing sleeve decreases the rigidity of the cannula; and a needle movably disposed within the second lumen and coupled to at least one operable toggle, wherein when at least one operable toggle is activated, the needle extends from the second lumen at the distal end of the cannula and retracts into the second lumen.

[0374] Embodiment 70: The surgical instrument according to Embodiment 69, wherein the reinforcing sleeve includes a hollow tubular body.

[0375] Embodiment 71: The surgical instrument according to Embodiment 70, wherein the reinforcing sleeve is formed of a metallic material including at least one of stainless steel, aluminum, or titanium.

[0376] Embodiment 72: The surgical instrument according to Embodiment 70, wherein the reinforcing sleeve is formed of a composite material comprising at least one of polyetheretherketone (PEEK), polyetherketone (PEK), polytetrafluoroethylene (PTFE), or polycarbonate (PC).

[0377] Embodiment 73: The surgical instrument according to Embodiment 69, wherein the position of the reinforcing sleeve along the length of the cannula is releasably lockable.

[0378] Embodiment 74: A surgical instrument for fluid injection, comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and at least one operable toggle movably coupled to a handle; a cannula indirectly coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough; a needle movably disposed within the second lumen and coupled to at least one operable toggle, configured to extend from the second lumen at the distal end of the cannula and retract into the second lumen when the operable toggle is activated; and a shaft adapter for coupling the cannula to the handpiece, wherein the shaft adapter has a curvature such that the longitudinal axis of at least a portion of the cannula is non-parallel to the longitudinal axis of the handpiece.

[0379] Embodiment 75: The surgical instrument according to Embodiment 74, wherein the shaft adapter includes a curved, hollow tubular body.

[0380] Embodiment 76: The surgical instrument according to Embodiment 74, wherein the cannula is configured to extend from the distal end of the shaft adapter and retract into it when at least one operable toggle is activated.

[0381] Embodiment 77: The surgical instrument according to Embodiment 74, wherein the shaft adapter is formed of a metallic material including at least one of stainless steel, aluminum, or titanium.

[0382] Embodiment 78: The surgical instrument according to Embodiment 74, wherein the shaft adapter has a radius of curvature of approximately 1 mm to approximately 20 mm.

[0383] Embodiment 79: An entry cannula for inserting a surgical instrument into the eye, comprising a hollow body having a distal end, a proximal end, and a central channel extending from the distal end to the proximal end, the hollow body having a non-circular cross-sectional profile, a distal portion located at the distal end of the hollow body having a wedge-shaped form, and a proximal portion located at the proximal end of the hollow tubular body having a tubular form.

[0384] Embodiment 80: The entry cannula according to Embodiment 79, wherein the hollow body includes a flat cross-sectional profile having an elliptical, oblong, or tablet-like shape.

[0385] Embodiment 81: The entry cannula according to Embodiment 79, wherein the distal portion includes a notch formed in the side wall of the hollow body.

[0386] Embodiment 82: An entry cannula according to Embodiment 79, wherein the distal and proximal portions are formed from the same material.

[0387] Embodiment 83: The entry cannula according to Embodiment 79, wherein the distal and proximal portions are formed of different materials.

[0388] Embodiment 84: The entry cannula according to Embodiment 79, further comprising one or more fixing arms coupled to the proximal portion and extending laterally from the proximal portion, the one or more fixing arms for securing the entry cannula when inserted into the eye.

[0389] Embodiment 85: An entry cannula according to Embodiment 84, wherein one or more fixing arms are firmly coupled to the proximal portion.

[0390] Embodiment 86: An entry cannula according to Embodiment 84, wherein one or more fixing arms are extended to the proximal portion so as to be able to extend laterally outward from the proximal portion and retract laterally inward toward the proximal portion.

[0391] Embodiment 87: An entry cannula for inserting a surgical instrument into the eye, comprising a tubular portion having a distal end, a proximal end, and a central channel extending from the distal end to the proximal end, further comprising an end face located at the distal end and oriented at an angle not perpendicular to the longitudinal principal axis of the tubular portion to form a wedge shape, and a funnel portion coupled to the proximal end of the tubular portion having a funnel shape for facilitating the insertion of a surgical instrument into the tubular portion.

[0392] Embodiment 88: The entry cannula according to Embodiment 87, wherein the funnel portion includes a semi-funnel shape formed by a hyperbolic wall bonded to a flat wall.

[0393] Embodiment 89: An entry cannula according to Embodiment 88, wherein the position of the planar wall of the funnel portion corresponds to the orientation of the end face of the tube portion.

[0394] Embodiment 90: A surgical instrument for fluid injection, comprising a handpiece configured for user gripping, formed of a lightweight thermoplastic material and including a first lumen disposed therein and an operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, including a second lumen extending therethrough; a needle movably disposed within the second lumen and coupled to the operable toggle, configured to extend from the second lumen at the distal end of the cannula and retract into the second lumen when the operable toggle is activated, the surgical instrument being configured to hang freely without damaging the eye when inserted into the eye.

[0395] Embodiment 91: The surgical instrument according to Embodiment 90, wherein the lightweight thermoplastic material comprises at least one of polyetheretherketone (PEEK), polyetherketone (PEK), or polytetrafluoroethylene (PTFE).

[0396] Embodiment 92: The surgical instrument according to Embodiment 90, wherein the operable toggle includes a sliding button.

[0397] Embodiment 93: The surgical instrument according to Embodiment 90, wherein the handpiece includes a fastening device disposed on its outer surface, the fastening device being for securing the surgical instrument to a patient.

[0398] Embodiment 94: The fastening device is a surgical instrument according to Embodiment 93, comprising a Velcro® strip.

[0399] Embodiment 95: A system for performing an injection into the subretinal space of an eye, comprising: an expandable guide cannula for passing through the suprachoroidal space of the eye, the expandable guide cannula configured to expand laterally; and a first channel extending from the proximal to the distal end of a flexible tubular member, wherein the lateral expansion of the flexible tubular member increases the lateral dimension of the first channel, facilitating the entry of an injection cannula through the expandable guide cannula; the injection cannula is configured to extend into the first channel, and the injection cannula comprises the first channel including a lumen that extends at least partially, and a needle movably positioned within the lumen, wherein the needle is configured to extend out of the lumen at the distal end of the injection cannula and retract into the lumen.

[0400] Embodiment 96: The system according to Embodiment 95, wherein the flexible tubular member further includes a second channel located within its side wall, and the flexible tubular member is expanded by filling the second channel with a working fluid.

[0401] Embodiment 97: The system according to Embodiment 95, wherein the expandable guide cannula further includes a hub configured to contact the surface of the eye and secure the expandable guide cannula.

[0402] Embodiment 98: The system according to Embodiment 97, wherein the hub includes a port for filling a portion of the flexible tubular member with a working fluid to expand the flexible tubular member.

[0403] Embodiment 99: The system according to Embodiment 97, wherein the hub includes an inclined inner surface for mechanically guiding the infusion cannula during insertion of the infusion cannula into the expandable guidance cannula.

[0404] Embodiment 100: The system according to Embodiment 95, wherein the flexible tubular body is formed of at least one of silicone, polyurethane (PUR), polyether block amide (PEBA), or polyolefin.

[0405] Embodiment 101: The system according to Embodiment 100, wherein the hub is formed of the same material as the flexible tubular body.

[0406] Embodiment 102: The system according to Embodiment 100, wherein the hub is formed of a rigid or non-expandable material.

[0407] Embodiment 103: The system according to Embodiment 95, wherein a flexible tubular member is coupled to a braided wire, and the flexible tubular member is expanded by twisting the braided wire.

[0408] Embodiment 104: A surgical system for fluid injection, comprising an injection device, the injection device comprising: a handpiece configured for user gripping, comprising a first lumen disposed therein and an operable toggle movably coupled to a handle; a cannula coupled to the handpiece and configured to be introduced into the eye, comprising a second lumen extending therethrough and a distal tip at the distal end of the cannula; a needle movably disposed within the second lumen and coupled to the operable toggle, configured to extend from the second lumen and retract into the second lumen at the distal tip of the cannula when the operable toggle is activated, and at least one of the distal tip or the needle being formed of a magnetic material; and one or more electromagnetic coils, the one or more electromagnetic coils configured to generate a one-dimensional, two-dimensional or three-dimensional magnetic f...

Claims

1. A device for performing subretinal injection into the subretinal space of the eye, wherein the device is An injection needle having a proximal end and a distal end, wherein the distal end is configured to be insertable into the subretinal space at a position on the surface of the retina, An inserter device detachably coupled to the injection needle, A conduit having a distal end connected to the proximal end of the injection needle and a proximal end connected to a fluid source, the conduit having a first lumen and a second lumen, and being positioned through the inserter device, The injection needle includes a stabilizer configured to fix the injection needle to the position on the surface of the retina, The fluid source comprises a first fluid reservoir for containing a non-treatment solution and a second fluid reservoir for containing a treatment solution, the fluid source is configured to provide the non-treatment solution from the first fluid reservoir to the subretinal space via the first lumen, and the fluid source is configured to provide the treatment solution from the second fluid reservoir to the subretinal space via the second lumen.

2. The apparatus according to claim 1, wherein the injection needle further includes a connector piece, and the stabilizer is movably coupled to the connector piece.

3. The apparatus according to claim 2, wherein the stabilizer is configured to translate along the connector piece between an inactive position and an active position to fix the injection needle to the position on the surface of the retina, and the stabilizer is located outside the connector piece in both the inactive and active positions.

4. The apparatus according to claim 3, wherein the stabilizer includes a plurality of bendable legs, the plurality of bendable legs are configured to be extended in the inactive position and bent in the active position.

5. The apparatus according to claim 4, wherein the plurality of bendable legs are connected to an extension ring at the proximal end of each of the plurality of bendable legs, the extension ring is configured to surround the connector piece and to translate along the connector piece, and distal movement of the extension ring causes the plurality of bendable legs to bend.

6. The apparatus according to claim 1, wherein the conduit further includes a third lumen, the stabilizer is movably coupled to the distal end of the third lumen, and pressure or fluid applied through the third lumen is configured to extend the stabilizer beyond the distal end of the third lumen.

7. The apparatus according to claim 6, wherein the fluid source further includes a third fluid reservoir, and the fluid source is configured to provide a working fluid from the third fluid reservoir through the third lumen to extend the stabilizer.

8. The apparatus according to claim 1, wherein the stabilizer includes an elastic balloon.

9. The apparatus according to claim 8, wherein the balloon is extended beyond the distal end of the third lumen of the conduit by filling it with a working fluid comprising at least one of perfluorocarbon solution (PFCL), BSS, physiological saline, air, or N2.

10. The apparatus according to claim 1, wherein the inlet device is configured to be separated from the conduit outside the eye after being separated from the injection needle.

11. A method for performing subretinal injection into the subretinal space of the eye, wherein the method is: The method of insertion involves inserting the distal end of an injection needle into the subretinal space at a target site on the surface of the retina, wherein the injection needle has a proximal end connected to the distal end of a conduit, the conduit has a proximal end connected to a fluid source, and the proximal end of the injection needle is further detachably connected to the distal end of an injector device. The injection needle is fixed to the target site on the surface of the retina by applying pressure or fluid through the first lumen of the conduit to extend the stabilizer beyond the distal end of the first lumen so that it contacts the surface of the retina, Separating the inserter device from the injection needle, To provide a non-therapeutic solution from the fluid source to the subretinal space via the second lumen of the conduit, A method comprising using the fluid source to deliver a therapeutic solution to the subretinal space through the third lumen of the conduit.

12. The method according to claim 11, wherein providing each of the non-therapeutic solution and the therapeutic solution is performed hands-free.

13. The method according to claim 11, wherein the non-therapeutic solution and the therapeutic solution are provided simultaneously.

14. The method according to claim 11, wherein each of the non-therapeutic solution and the therapeutic solution is carried out sequentially.

15. The method according to claim 11, wherein the stabilizer is coupled to the distal end of the first lumen, and applying the pressure or fluid through the first lumen includes providing a working fluid to the first lumen from the fluid source.

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