Method and apparatus for subretinal injection

Abstract

In some embodiments, a device is provided for performing a subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of an eye. The device includes a needle (110) having a proximal end (112) and a distal end (114), the distal end (114) configured to be insertable into the subretinal space at a location on the surface of the retina. The device includes a multi-lumen tube (120) having a distal end (122) coupled to the proximal end (112) of the needle (110) and a proximal end coupled to a fluid control unit. The device includes a stabilizer (130) configured to immobilize the needle (110) at its location on the surface of the retina. The fluid control unit has multiple fluid reservoirs containing a non-therapeutic solution, a therapeutic solution, and a working fluid that are injectable into the eye via separate lumens (128a, 128b, 128c) of the multi-lumen tube (120).

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 141,051, filed on January 25, 2021, entitled "METHOD AND APPARATUS FOR SUBRETINAL INJECTION", inventors Niels Alexander Abt and Reto Grueebler, and incorporates this in its entirety by reference herein as if fully and completely set forth herein.

[0002] Embodiments of the present disclosure generally relate to devices for ophthalmic treatment, and more particularly, to devices and methods for performing subretinal injection. Subretinal injection generally refers to the injection of fluid or other therapeutic substances or stem cells into the subretinal space between the retina of the eye and the retinal pigment epithelium (RPE).

Background Art

[0003] For example, several diseases of the eye, including age - related macular degeneration (AMD), retinal degenerative diseases, and genetic defects, are treatable by injection into the subretinal space. In a typical implementation, at least two people are required to perform a subretinal injection. For example, a surgeon in command can guide an injection instrument, such as a syringe / needle, and visually monitor the injection site, while a skilled surgical assistant can push the fluid out of the syringe and monitor the injection volume. Thus, generally, a first syringe is prepared with a small - gauge needle and contains a non - therapeutic fluid, such as 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 handles the first syringe and visually monitors the injection site, the assistant manually injects the non - therapeutic fluid and monitors the injection volume. Then, the first syringe is removed from the eye.

[0004] A second syringe is prepared, equipped with a small-gauge needle and containing a therapeutic fluid, such as a therapeutic agent. In the second step of the procedure, the second syringe is inserted through the retina into the subretinal space, at approximately the same location as the first syringe. While the surgeon handles the second syringe and visually monitors the injection site, an assistant manually injects the therapeutic fluid and monitors the injection volume. Therefore, there are many disadvantages to using a handheld injection device when manually controlling the injection in a two-step process. Some of these disadvantages are described below.

[0005] Firstly, as mentioned above, administering fluids with a handheld infusion device can lead to retinal tears. In particular, retinal tears can result from inadequate movement of the syringe / needle due to external forces from outside the eye while the needle is being inserted through the retina. These external forces may include inadequate movements by the surgeon handling the syringe or by an assistant manually controlling the fluid injection.

[0006] Furthermore, manual control of fluid injection as described above can have several additional drawbacks. Generally, manual control of fluid injection requires manually pushing down the plunger. For example, manual control of fluid injection can lead to inaccurate injection volume, which can result in over- or under-dosing, or excessive retinal stretching. In another example, manual control of fluid injection can lead to high flow velocity into the subretinal space, which can damage the retina or RPE, causing retinal detachment such as rupture, accompanied by changes in retinal morphology or RPE atrophy. In yet another example, manual control of fluid injection can lead to high shear force on the needle, which can impair the biological activity of various therapeutic agents carried by the injected fluid, such as drugs, stem cells, or viral vectors.

[0007] Furthermore, as mentioned above, removing the first needle and inserting the second needle through the retina may have additional drawbacks. For example, multiple insertions through the retina may contribute to retinal tearing. In another example, creating two different holes in the retina, one with each injection step, increases the likelihood of fluid leakage from the subretinal space. [Overview of the project] [Problems that the invention aims to solve]

[0008] Each of the aforementioned problems can adversely affect and / or increase safety risks in ophthalmic treatments being performed. Therefore, there is a need in the industry for improved ophthalmic treatment equipment, including improved devices and methods for subretinal injection. [Means for solving the problem]

[0009] This disclosure relates, in general terms, to devices for ophthalmic treatment, and more particularly to devices and methods for subretinal injection.

[0010] In some embodiments, a device is provided for performing subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of the eye. The device includes a needle having a proximal end and a distal end, the distal end being configured to be insertable into the subretinal space at a certain position on the surface of the retina. The device includes a multi-lumen tube having a distal end coupled to the proximal end of the needle and a proximal end coupled to a fluid control unit, the multi-lumen tube having a first lumen and a second lumen. The device includes a stabilizer configured to immobilize the needle at a certain position on the surface of the retina. The fluid control unit has a first fluid reservoir containing a non-therapeutic solution and a second fluid reservoir containing a therapeutic solution. The fluid control unit is configured to inject the non-therapeutic solution from the first fluid reservoir into the subretinal space via the first lumen, and to inject the therapeutic solution from the second fluid reservoir into the subretinal space via the second lumen.

[0011] In some embodiments, methods are disclosed for subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of the eye. The method includes inserting the distal end of a needle into the subretinal space at a location on the surface of the retina, wherein the needle has a proximal end coupled to the distal end of a multilumen tube, and the multilumen tube has a proximal end coupled to a fluid control unit. The method includes immobilizing the needle at a location on the surface of the retina by applying pressure or fluid through a first lumen of the multilumen tube, thereby expanding a stabilizer beyond the distal end of the first lumen and bringing it into contact with the surface of the retina. The method includes injecting a non-therapeutic solution from the fluid control unit into the subretinal space via a second lumen of the multilumen tube. The method includes injecting a therapeutic solution into the subretinal space via a third lumen of the multilumen tube using the fluid control unit.

[0012] To enable a more detailed understanding of the features of this disclosure described above, a more detailed description of this disclosure, which is briefly summarized above, is given with reference to embodiments, some of which are shown in the accompanying drawings. However, it should be noted that the accompanying drawings are only illustrative embodiments and should not be considered limiting in scope, and other equally effective embodiments may be recognized. [Brief explanation of the drawing]

[0013] [Figure 1A] This is a schematic diagram of an exemplary injection device for subretinal injection according to several embodiments. [Figure 1B] This is a transverse cross-section of a portion of the eye, showing the retina and retinal pigment epithelium. [Figure 1C] This is an enlarged cross-sectional view taken along the cross-sectional line of Figure 1A, showing an exemplary multi-lumen tube according to several embodiments. [Figure 1D] Figure 1A is an isometric view of the upper part of a portion of the injection device. [Figure 2A] This is a schematic diagram of an exemplary inserter device that may be used with the injection device described herein, according to several embodiments. [Figure 2B] This is a schematic diagram of another exemplary inserter device that may be used with the injection device described herein, according to several embodiments. [Figure 2C] Figure 1A is a schematic diagram of an injection apparatus showing a combined exemplary inserter device according to several embodiments. [Figure 2D] Figure 2C is an enlarged longitudinal section of a portion of the diagram showing an exemplary injection needle used in conjunction with the injection device described herein, according to several embodiments. [Figure 3] This is an isometric view of an exemplary injection device for performing subretinal injection, used in operation according to several embodiments. [Figure 4] This figure illustrates a method for performing subretinal injection according to several embodiments. [Figure 5A] This is a cross-sectional view of the eye in different operations of the method shown in Figure 4, according to several embodiments. [Figure 5B] This is a cross-sectional view taken along the cross-sectional line of 5A according to several embodiments. [Figure 6A] This is a cross-sectional view of the eye in different operations of the method shown in Figure 4, according to several embodiments. [Figure 6B] This is a cross-sectional view taken along the cross-sectional line of 6A according to several embodiments. [Figure 7A] This is a cross-sectional view of the eye in different operations of the method shown in Figure 4, according to several embodiments. [Figure 7B] This is a cross-sectional view taken along the cross-sectional line of 7A according to several embodiments. [Figure 7C] This is an enlarged cross-sectional view of a portion of Figure 7A, showing an exemplary stabilizer that may be used with the injection apparatus described herein, according to several embodiments. [Figure 8A] This is a cross-sectional view of the eye in different operations of the method shown in Figure 4, according to several embodiments. [Figure 8B] This is a cross-sectional view taken along the cross-sectional line of 8A according to several embodiments. [Figure 9A] Cross-sectional views of the eye in different operations of the method of FIG. 4, according to some embodiments. [Figure 9B] Cross-sectional view taken along section line 9A, according to some embodiments. [Figure 9C] Enlarged cross-sectional view of a portion of FIG. 9A showing the formation of a bleb in the subretinal space, according to some embodiments. [Figure 10A] Cross-sectional views of the eye in different operations of the method of FIG. 4, according to some embodiments. [Figure 10B] Cross-sectional view taken along section line 10A, according to some embodiments. [Figure 11A] Cross-sectional views of the eye in different operations of the method of FIG. 4, according to some embodiments. [Figure 11B] Cross-sectional view taken along section line 11A, according to some embodiments. [Figure 12A] Cross-sectional views of the eye in different operations of the method of FIG. 4, according to some embodiments. [Figure 12B] Cross-sectional view taken along section line 12A, according to some embodiments. [Figure 13A] Isometric view of another exemplary injection needle that can be used with the injection device described herein, according to some embodiments. [Figure 13B] Vertical cross-sectional view of the injection needle of FIG. 13A showing the injection needle inserted into the subretinal space, according to some embodiments. [Figure 14A] Isometric view of yet another exemplary injection needle that can be used with the injection device described herein, according to some embodiments. [Figure 14B] Vertical cross-sectional view of the injection needle of FIG. 14A showing the injection needle inserted into the subretinal space, according to some embodiments. [Figure 15] Isometric view of the upper portion of another exemplary stabilizer that can be used with the injection device described herein, according to some embodiments. [Figure 16]This is an isometric view of the top of yet another exemplary stabilizer, which may be used in conjunction with the injection device described herein, according to some embodiments. [Figure 17] This is an isometric view of the top of yet another exemplary stabilizer, which may be used in conjunction with the injection device described herein, according to some embodiments. [Figure 18] This is a schematic diagram of an exemplary guidewire that may be used with an injection device described herein, according to several embodiments. [Modes for carrying out the invention]

[0014] For ease of understanding, the same reference numerals are used to specify identical elements common to multiple drawings, where possible. Elements and features of one embodiment may be usefully incorporated into other embodiments without further description.

[0015] This disclosure relates, in general terms, to devices for ophthalmic treatment, and more particularly to devices and methods for subretinal injection.

[0016] Embodiments of this disclosure describe a device for performing subretinal injection. Generally, the device includes a needle attached to a tube, which may be fixed in the eye using a stabilizer, so that the injection device does not need to be held throughout the entire procedure. This provides detachment of the needle from undesirable movements that would otherwise occur when the injection device is handheld. Furthermore, the device's tube is coupled to a fluid pump located outside the eye to automate the actual fluid injection process. Automated control of fluid injection can improve control over the injection volume, as well as control over important flow parameters of the injected fluid, compared to manual control of fluid injection. Furthermore, the device's tube is a multi-lumen tube, which provides multiple parallel flow paths from separate fluid reservoirs to the injection needle, so that the injection can be performed using only one needle. The need to insert only one needle through the retina can reduce retinal damage that could otherwise occur from repeated punctures of the retina.

[0017] Figure 1A is a schematic diagram of an exemplary injection device 100 for performing subretinal injection. Figure 1B is a cross-sectional view of a portion of an eye 10. Therefore, Figures 1A and 1B are described together in this specification for clarity. In particular, the injection device 100 is configured to perform subretinal injection into the subretinal space 50 between the retina 20 and the retinal pigment epithelium (RPE) 30 of the eye 10 (Figure 1B). As shown in Figure 1A, the injection device 100 generally includes a needle 110, a multi-lumen tube 120, a stabilizer 130, and a fluid control unit 140.

[0018] Referring to Figure 1A, the injection needle 110 has a proximal end 112 and a distal end 114. The distal end 114 of the injection needle 110 is configured to be inserted into the subretinal space 50 at a target position on the surface 22 of the retina 20 (Figure 1B). The injection needle 110 includes a connector piece 116 (described in more detail below) at its proximal end 112 that connects the injection needle 110 to a multi-lumen tube 120. The multi-lumen tube 120 has a distal end 122 attached to the proximal end 112 of the injection needle 110 by the connector piece 116, and a proximal end 124 attached to a fluid control unit 140.

[0019] Figure 1C is an enlarged cross-sectional view taken along the section line of Figure 1A, showing an exemplary multi-lumen tube 120. The multi-lumen tube 120 includes an outer wall 126o surrounding three lumens 128a, 128b, and 128c. Although Figure 1C shows three lumens, more or fewer lumens may be used (e.g., two or more lumens, two to four lumens, two lumens, or four lumens). Lumens 128a-c are divided by an inner wall 126i connected to the outer wall 126o. Lumens 128a-c radially surround the central longitudinal axis 120x of the multi-lumen tube 120. In the embodiment of Figure 1C, one or more of the lumens 128a-c have different sizes. For example, each of lumens 128a and 128b extends circumferentially to a quarter of the multi-lumen tube 120. On the other hand, lumen 128c extends circumferentially to half of the multi-lumen tube 120. Therefore, in the embodiment of Figure 1C, the volume of lumen 128c may be twice the volume of lumens 128a and 128b, respectively. In some other embodiments, each of lumens 128a-c has the same size. In some embodiments, the multi-lumen tube 120 is formed from polymers such as silicone, polyurethane (PUR), polyamide (PA) (e.g., nylon), polyethylene (PE), polyether block amide (PEBA), polytetrafluoroethylene (PTFE), polyimide (PI), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), polyether ether ketone (PEEK), liquid crystal polymer (LCP), ethylene tetrafluoroethylene (ETFE), tetrafluoroethylene and hexafluoropropylene and vinylidene fluoride terpolymer (THV), thermoplastic elastomer (TPE), or combinations thereof. In some embodiments, the injection needle 110 and the multi-lumen tube 120 are formed from the same or different materials.

[0020] The fluid control unit 140 includes a fluid pump 142 that drives the flow through a multi-lumen tube 120. Figure 1A shows a syringe pump, but the fluid pump 142 may include a Vernier Flow Control (VFC) pump, or at least one of other types of pressure-controlled pumps, volume-controlled pumps, variable-volume-controlled pumps, peristaltic pumps, lever-actuated pumps, valve-actuated pumps, or venturi pumps. The fluid control unit 140 also includes three fluid reservoirs 144a, 144b, and 144c for storing multiple fluids 145a-c. Figure 1A shows three fluid reservoirs, but more or fewer fluid reservoirs may be used. Referring to Figure 1A, each of the fluid reservoirs 144a-c is a syringe configured to be actuated by a syringe pump. In some embodiments, the multiple fluids 145a-c include a non-therapeutic solution 145a, a therapeutic solution 145b, and a working fluid 145c.

[0021] During operation, the fluid pump 142 is configured to drive the flow of multiple fluids 145a-c from each of the fluid reservoirs 144a-c through each of the lumens 128a-c of the multi-lumen tube 120 (Figure 1C). As will be further described below, when the injection needle 110 is first inserted into the retina 20, the working fluid 145c is initially configured to flow through port 118c of connector piece 116 (Figure 1D) to expand the stabilizer 130 and stabilize the injection needle 110. Subsequently, the non-therapeutic solution 145a and therapeutic solution 145b are configured to flow through ports 118a and 118b of connector piece 116 (Figure 1D) respectively to inject the fluids 145a and 145b into the subretinal space 50 (Figure 1B) separately. Note that Figure 1A shows the stabilizer 130 in the expanded state. Additional details regarding the operation of the stabilizer 130 are provided with reference to Figure 1D.

[0022] In some embodiments, the non-therapeutic solution 145a comprises an ophthalmic irrigation solution (e.g., BSS) having a physiological pH and osmotic pressure. In some embodiments, the therapeutic solution 145b comprises a therapeutic substance for treating the eye 10 (e.g., anti-VEGF, tissue plasminogen activator (tPA), stem cells, viral vectors for gene therapy, other drugs, or a combination thereof). In some embodiments, the working fluid 145c comprises a fluid for expanding the stabilizer 130 (e.g., perfluorocarbon solution (PFCL), BSS, saline solution, air, N2, other liquids or gases, or a combination thereof).

[0023] The fluid control unit 140 includes a controller 146 for controlling the operation of the fluid pump 142. In some embodiments, the controller 146 includes a wireless receiver 147a having an antenna 147b for receiving commands wirelessly from a control console. The fluid control unit 140 includes a power supply 148 for powering the fluid pump 142 and the controller 146. In some embodiments, the power supply 148 includes at least one of a battery, one or more springs, or a gas container. In some other embodiments, power is provided by gravity or at least one of manual operation. In some other embodiments, the fluid control unit 140 also includes a plurality of valves for regulating the fluid flow from fluid reservoirs 144a-c.

[0024] Figure 1D is an isometric view of the upper part of a portion of the injection device 100 shown in Figure 1A. Referring to Figure 1D, the connector piece 116 has three ports 118a, 118b, and 118c located inside, corresponding to the distal ends of lumens 128a to c of the multi-lumen tube 120. The two separate ports 118a and 118b of the connector piece 116 merge into one toward the distal end 114 of the injection needle 110. On the other hand, port 118c is separate from and fluidly isolated from ports 118a and 118b. Port 118c is fluidly coupled to the stabilizer 130 as shown.

[0025] Referring to Figures 1A and 1D, the stabilizer 130 is shown in an extended or operational position, where it extends from the port 118c of the connector piece 116. In the extended position, the stabilizer 130 helps to stabilize the injection needle 110 and control the location of the injection of the non-therapeutic solution 145a, thereby forcing the location of the bleb, which will be described in more detail below with reference to Figures 4 and 9A-9C. In the embodiments of Figures 1A and 1D, the stabilizer 130 is a balloon 132 or bag having a pair of wings 132a, 132b. In some other embodiments, the balloon 132 may have any preferred shape, including, but not limited to, round, oval, or polygonal. The balloon 132 may be formed from plastic, metal, polymer, nitinol, or a combination thereof.

[0026] Before the stabilizer 130 reaches the extended position shown in Figures 1A and 1D, it is positioned within the port 118c of the connector piece 116, as shown in Figure 2D and described in detail below. In some embodiments, to actuate the stabilizer 130 to the extended position, working fluid 145c (e.g., PFCL) is injected from the fluid reservoir 144c (Figure 1A) of the fluid control unit 140 through the lumen 128c, filling the balloon 132 with PFCL. In the extended position, the wings 132a and 132b of the balloon 132 extend substantially along an axis perpendicular to the central longitudinal axis 120x of the multi-lumen tube 120. In some embodiments, in the extended position, the balloon 132 has a flattened profile. For example, in some embodiments, the width of the balloon 132 measured parallel to the surface 22 of the retina 20 is greater than the height of the balloon 132 measured perpendicular to the surface 22 (e.g., at least twice as large, at least five times as large, or at least ten times as large). A flattened profile is beneficial because it increases the contact surface area between the balloon 132 and the surface 22. In some embodiments, the balloon 132 is held in place primarily by the weight of the working fluid 145c inside the balloon 132. Note that Figures 1A and 1D show only examples of stabilizers. Additional examples that may operate differently are further described with respect to Figures 15-17.

[0027] In the expanded position, the stabilizer 130 is configured to immobilize the injection needle 110 at the target position on the surface 22 of the retina 20, thereby reducing the possibility of the injection needle 110 being removed from the subretinal space 50 during treatment due to accidental light force. Immobilizing the injection needle 110 as used herein generally refers to restricting the movement of the injection needle 110 relative to the retina 20 in order to maintain the injection needle 110 at the target position on the surface 22 of the retina 20 throughout the treatment. That is, immobilizing the injection needle 110 does not mean restricting the injection needle 110 to zero or no movement at all. Instead, the injection needle 110 should still retain some limited degrees of freedom while maintained at the target position so that light and / or accidental forces can be safely applied without tearing the retina 20. Furthermore, the injection needle 110 should still be removable from the retina 20 if sufficient force is applied to it, even in the expanded position. Enabling the removal of the injection needle 110 in response to a sufficiently large tensile force prevents injury to the eye 10, i.e., serious laceration. Additional details regarding the stabilizer 130 and its operation are provided with reference to Figures 5-12.

[0028] Figure 2A is a schematic diagram of an exemplary inserter device 250 that may be used with the injection device 100 described herein. Generally, the inserter device 250 is configured to be releasably coupled to the injection needle 110 to provide a rigid structure for inserting the injection needle 110 into the eye 10 and further into the subretinal space 50. The inserter device 250 includes a cannula 254, which is the portion of the inserter device 250 that directly engages with the injection needle 110 and is insertable into the eye 10. The cannula 254 has a bore for surrounding the multi-lumen tube 120. In the embodiment of Figure 2A, the cannula 254 has an enclosed bore that extends longitudinally from its proximal end 254a to its distal end 254b.

[0029] The cannula 254 extends from a body 256, which is part of an inserter device 250 configured to be grasped and handled by a surgeon or surgical assistant. The body 256 has a needle release knob 258 for releasing the needle 110 from the cannula 254 once the needle 110 is properly positioned and immobilized within the eye 10. The release knob 258 may function in several different ways. For example, the release knob 258 may be a slide that moves a release mechanism to disengage the cannula 254 from the connector piece 116, allowing the cannula 254 to be retracted away from the needle 110. In some embodiments, the release mechanism includes a pair of inner and outer tubes surrounding the connector piece 116, each having an opening, and the inner tube is rotated to align these openings and release the needle 110. In some other embodiments, the release mechanism includes a conical tube that moves inside a ring surrounding and holding the connector piece 116, and by inserting the conical tube, the inner diameter of the ring is increased to release the injection needle 110. In some other embodiments, the release mechanism includes two hemishells that surround the connector piece 116 and are held together by the ring, and by moving the ring, the injection needle 110 is released. Alternatively, the cannula 254 may be spring-loaded, and by pressing the release knob 258, the cannula 254 is retracted away from the injection needle 110. Alternatively, by using a U-shaped cannula 264 (described in more detail below), the release knob 258 pushes the cannula 264 to one side, thereby disengaging the cannula 264 from the connector piece 116 through a slit 265 formed along the length of the cannula 264. In the embodiment shown in Figure 2A, the inserter device 250 is configured to remain connected to the multi-lumen tube 120 located outside the eye 10, so that the enclosed bore prevents the cannula 254 from being removed from around the multi-lumen tube 120. Note that Figure 2A shows only one example of an inserter device. Additional examples that may operate differently are further described in Figure 2B.

[0030] Figure 2B is a schematic diagram of another exemplary inserter device 260 that may be used with the infusion device 100 described herein. Referring to Figure 2B, the inserter device 260 is constructed and arranged similarly to the inserter device 250 of Figure 2A, except as noted, and its corresponding description may be incorporated herein, but is not limiting. In one or more embodiments, the cannula 264 has a slit 265 that extends longitudinally from its proximal end 264a to its distal end 264b. In some embodiments, the cross-section of the cannula 264 is U-shaped. In some embodiments, the minimum width of the slit 265 is greater than the outer diameter of the multi-lumen tube 120. In such embodiments, the inserter device 260 is configured to detach the multi-lumen tube 120 from the multi-lumen tube 120 outside the eye 10 by sliding the multi-lumen tube 120 through the slit 265.

[0031] Figure 2C is a schematic diagram of the infusion apparatus 100 of Figure 1A, showing an exemplary inserter device 250 in combination. Figure 2D is an enlarged longitudinal section of a portion of Figure 2C, showing an exemplary injection needle 110 used in conjunction with the infusion apparatus 100 described herein. Therefore, Figures 2C-2D are described together herein for clarity. The infusion apparatus 100 is shown in a configuration ready to begin a subretinal injection procedure. For example, the inserter device 250 is coupled to the injection needle 110, and the cannula 254 of the inserter device 250 surrounds the multi-lumen tube 120. Furthermore, the stabilizer 130 is in a retracted position, located inside the port 118c of the connector piece 116, which is positioned within the distal end 254b of the cannula 254. Figure 2D shows the straight injection needle 110. In other words, the injection needle 110 extends from its proximal end 112 to its distal end 114 at a constant angle substantially parallel to the central longitudinal axis 120x of the multi-lumen tube 120. In some embodiments, as shown in Figure 2D, the cannula 254 of the inserter device 250 extends beyond the distal end 122 of the multi-lumen tube 120 and surrounds the connector piece 116 of the injection needle 110. In some embodiments of Figure 2D, the inner diameter of the cannula 254 corresponds to the outer diameter of the connector piece 116.

[0032] Figure 3 is an isometric view of an exemplary injection device 300 for performing subretinal injection. Referring to Figure 3, the injection device 300 is used in conjunction with a surgical microscope 302 and an operating table 304. In some optional embodiments shown in Figure 3, the fluid control unit 140 is mounted on the surgical microscope 302. In some other optional embodiments shown in Figure 3, the fluid control unit 140 is mounted and / or placed on the forehead 62 of a patient 60 lying on the operating table 304. Several advantages are associated with the positioning of the fluid control unit 140 on the surgical microscope 302 or on the forehead 62, as described below and shown in Figure 3.

[0033] The first advantage is that attaching the fluid control unit 140 to a stationary object reduces the likelihood of external forces being applied to the multi-lumen tube 120, thereby reducing the likelihood of the injection needle 110 protruding or tearing the retina 20. In other words, attaching the fluid control unit 140 to a stationary object helps to achieve isolation of the fluid control unit 140 from a moving object, thereby reducing the influence of external forces.

[0034] Another advantage is that by positioning the fluid control unit 140 very close to the eye 10 (e.g., on the surgical microscope 302 or forehead 62), the relative overall length of the multi-lumen tube 120 is shortened compared to some other embodiments where the fluid control unit 140 is positioned further away from the eye 10. This reduces the dead volume of each of the multiple fluids 145a-c in the multi-lumen tube 120 between the fluid reservoirs 144a-c and the eye 10. Since the cost of therapeutic treatment fluids is often very high, reducing fluid waste due to dead volume, for example in the multi-lumen tube 120, can lead to considerable cost savings. It is also conceivable that shortening the distance between the fluid control unit 140 and the eye 10 reduces the elasticity of the system, providing tighter fluid control.

[0035] In some other embodiments, the dead volume within the multi-lumen tube 120 can be reduced by using a microlumen tube having a smaller outer diameter and smaller flow cross-sectional area compared to a standard tube. For example, the outer diameter of a microlumen tube may be about 0.3 mm or less, while the outer diameter of a standard tube is considered to be about 0.4 mm.

[0036] In some other embodiments, the dead volume within the multi-lumen tube 120 can be reduced by introducing each of the multiple fluids 145a-c into the multi-lumen tube 120 from the front. In such embodiments, the injection needle 110 is configured to be removed from the distal end 122 (Figure 2D) of the multi-lumen tube 120 so that each of the multiple fluids 145a-c can be introduced directly into the distal end 122 of one of the lumens 128a-c. In other words, the multiple fluids 145a-c are stored within a portion of the multi-lumen tube 120 instead of in a fluid reservoir 144a-c. In such embodiments, the dead volume in the multi-lumen tube 120 upstream of the multiple fluids 145a-c (i.e., between the fluid reservoirs 144a-c and each of the multiple fluids 145a-c) can be filled with a relatively low-cost chaser fluid (e.g., air, N2, BSS, saline solution, other liquids or gases, or a combination thereof). In such embodiments, the chaser fluid is pressurized by a fluid pump 142, which then pressurizes the fluids stored in the multi-lumen tube 120. In some embodiments, lumen 128b is fed from the front with the relatively more expensive therapeutic solution 145b, while lumens 128a and 128c receive the non-therapeutic solution 145a and working fluid 145c from the fluid reservoirs 144a and 144c, respectively.

[0037] Figure 4 illustrates a method 400 for performing subretinal injection using the injection device 100 described herein. In preparation for subretinal injection, the sclera 12 is incised using a trocar cannula consisting of a valved cannula 152 (Figure 5A) and a trocar. Generally, a pre-packaged trocar cannula, having a hub at its proximal end, is inserted into the eye 10 until the bottom surface of the hub contacts the sclera 12. The trocar is then removed from the eye 10, and the valved cannula 152 is placed as shown in Figure 5A. Although not shown, in Figures 5A-12A, the bottom surface of the hub of the valved cannula 152 may be parallel to or coplanar with the surface of the eye 10. In operation 402, the cannula 254 of the inserter device 250 is inserted into the eye 10 through the valved cannula 152 (Figures 5A-5B).

[0038] In operation 404, the distal end 114 of the injection needle 110 is inserted into the subretinal space 50 at a target position on the surface 22 of the retina 20 (Figures 6A-6B). In some embodiments, the depth of the injection needle 110 is visually controlled. For example, in some embodiments, optical coherence tomography (OCT) image data may be used during surgery to visualize that the distal end 114 of the injection needle 110 is positioned within the appropriate layer of the eye 10, i.e., within the subretinal space 50. In some embodiments, a connector piece 116 acts as an end stopper to prevent the injection needle 110 from being inserted too far into the eye 10 (e.g., through the RPE 30 or Bruch's membrane 40), which could damage the eye 10 if inserted too far. In some embodiments, the length of the injection needle 110, measured from the connector piece 116 to its distal end 114, is selected so that the distal end 114 is correctly positioned between the retina 20 and the RPE 30 when the connector piece 116 contacts the surface 22 of the retina 20. In some embodiments, the length of the injection needle 110 may be selected based on a preoperative determination of the thickness of the retina 20.

[0039] In some other embodiments shown in Figures 13A-13B, the depth of the injection needle 1310 is controlled by using an end stopper 1300. In some other embodiments shown in Figures 14A-14B, the depth of the injection needle 1410 is controlled by using a curved injection needle 1410. Additional details regarding these embodiments are provided below.

[0040] In operation 406, the injection needle 110 is immobilized at a target position on the surface 22 of the retina 20 using a stabilizer 130. In some embodiments shown in Figures 7A-7C, pressure or fluid is applied through the lumen 128c of the multi-lumen tube 120 to expand the stabilizer 130 beyond the distal end 122 of the lumen 128c, positioning the stabilizer 130 in contact with the surface 22 of the retina 20. The stabilizer 130 is configured to make firm contact with the retina 20 so that the injection needle 110 is immobilized at a target position on the surface 22 of the retina 20. In some embodiments, the stabilizer 130 is formed from a material that matches the surface 22 of the retina 20 to increase the contact area between them.

[0041] In operation 408, after the stabilizer 130 has made contact with the surface 22 of the retina 20, the cannula 254 of the inserter device 250 is retracted from the eye 10 (Figures 8A-8B). After the cannula 254 is retracted, the injection needle 110 and the multi-lumen tube 120 are disconnected from external forces. As used herein, external forces generally include any force applied to the injection needle 110 or the multi-lumen tube 120 from outside the eye 10. For example, external forces generally include light and / or careless movements of any part of the infusion device 100 by a surgeon or surgical assistant. In some embodiments, disconnection limits the effect of external forces associated with the infusion of a non-therapeutic solution 145a (operation 410) or a therapeutic solution 145b (operation 412). As previously stated, in some other embodiments using a handheld infusion instrument to manually control the infusion in a two-step process, disconnection limits the effect of external forces associated with the movement of the handheld instrument.

[0042] In some embodiments shown in Figures 8A-8B, the excess length of the multi-lumen tube 120 is provided in an unrestrained state within the eye 10 to facilitate detachment. When an external force is applied to the multi-lumen tube 120, the excess length is recognized to allow the multi-lumen tube 120 to move within the eye 10 without transmitting force to the injection needle 110. In some embodiments using the inserter device 260 of Figure 2B, the inserter device 260 retracts the multi-lumen tube 120 by sliding it through the slit 265 and then detaches it from the multi-lumen tube 120.

[0043] In operation 410, the non-treatment solution 145a is injected from the fluid control unit 140 into the subretinal space 50 via the lumen 128a of the multi-lumen tube 120 (Figures 9A-9C). In some embodiments, for example, a fluid pump 142 drives the flow of the non-treatment solution 145a through the lumen 128a, injecting the non-treatment solution 145a from the fluid reservoir 144a into the subretinal space 50. In some embodiments, the injection of the non-treatment solution 145a forms a bleb in the subretinal space 50 between the retina 20 and the RPE 30 (Figure 9C). In some embodiments, the bleb is a localized hemispherical lifting of the retina 20, which is visible through a surgical microscope. Thus, the formation of a bleb by the non-treatment solution 145a provides visibility that the distal end 114 of the injection needle 110 is positioned in the appropriate layer of the eye 10, in the subretinal space 50.

[0044] In operation 412, the therapeutic solution 145b is injected from the fluid control unit 140 into the subretinal space 50 via the lumen 128b of the multi-lumen tube 120 (Figures 10A-10B). In some embodiments, a fluid pump 142 drives the flow of the therapeutic solution 145b through the lumen 128b, injecting the therapeutic solution 145b from the fluid reservoir 144b into the subretinal space 50. In some embodiments, the injection of the non-therapeutic solution 145a and the therapeutic solution 145b is performed hands-free. In some embodiments, the fluid pump 142 drives the flows of the non-therapeutic solution 145a, the therapeutic solution 145b, and the working fluid 145c without manually operating the multiple fluid reservoirs 144a-c. In some embodiments, the fluid pump 142 operates according to commands received from the controller 146. In some embodiments, the controller 146 receives control signals via a wireless receiver 147a. In some embodiments, a surgeon or surgical assistant may control the pressure or volume of each injection of several fluids 145a-c using a foot pedal that wirelessly communicates with a controller 146 via a wireless receiver 147a and an antenna 147b.

[0045] In operation 414, the injection needle 110 is remobilized by retracting the stabilizer 130 into the distal end 122 of the lumen 128c. Thus, the stabilizer 130 is removed from contact with the surface 22 of the retina 20. In some embodiments, the working fluid 145c is removed from the lumen 128c using vacuum pressure to retract the stabilizer 130 therein. In some embodiments, the stabilizer 130 is removed from contact with the surface 22 of the retina 20 without being retracted into the distal end 122 of the lumen 128c.

[0046] In operation 416, the multi-lumen tube 120 and the injection needle 110 coupled thereto are removed from the eye 10 (Figures 12A-12B). Without the stabilizer 130 coming into contact with the retina 20, the injection needle 110 can be removed from within the subretinal space 50 by a slight tensile force applied to the multi-lumen tube 120. In some embodiments, the retinal port formed by inserting the injection needle 110 through the retina 20 may be relatively small compared to a typical procedure, thanks to the various benefits of the apparatus and method disclosed herein. In such embodiments, the retinal port may be left unpatched without issue. In some other embodiments, the retinal port may be filled with a sealant (e.g., fibrin glue, collagen, cyanoacrylate, cellular attachment factors, fibronectin, laminin, extracellular matrix-based hydrogel, polyacrylic acid, zinc polycarboxylate cement, silicone adhesive, or ophthalmic viscosurgical device (OVD), or viscoelastic plug). In some other embodiments, the viscosity of the treatment solution 145b may be suitable for sealing the retinal port.

[0047] Various alternative embodiments are described in detail below. The following embodiments are recognized as being able to be combined with the injection device 100 and method 400, but are not limiting. Figure 13A is an isometric view of another exemplary injection needle 1310 that may be used with the injection device 100 described herein. Referring to Figure 13A, the end stopper 1300 is positioned around the injection needle 1310 between the proximal end 1312 and the distal end 1314. In the embodiment of Figure 13A, the end stopper 1300 is an annular disc having a central bore 1302 for receiving the injection needle 1310. The end stopper 1300 has first and second opposing faces 1304, 1306, which face each other parallel to the longitudinal axis of the central bore 1302. In some other embodiments, the end stopper 1300 may have a non-circular profile (e.g., polygonal or oval profile). In some embodiments, the inner diameter of the end stopper 1300 corresponds to the outer diameter of the injection needle 1310, forming an interlocking fit between them. In some other embodiments, the end stopper 1300 may be integral with the injection needle 1310, or it may be attached to the injection needle 1310 by adhesive or fasteners.

[0048] Figure 13B is a vertical cross-sectional view of the needle 1310 in Figure 13A, showing the needle 1310 being inserted into the subretinal space 50. When the distal end 1314 of the needle 1310 is inserted into the subretinal space 50, the second surface 1306 is in contact with the surface 22 of the retina 20. The distance between the distal end 1314 and the second surface 1306 is selected so that the distal end 1314 is properly positioned between the retina 20 and the RPE 30 when the second surface 1306 is in contact with the surface 22 of the retina 20. Therefore, the end stopper 1300 prevents the needle 1310 from being inserted too far into the eye 10 (e.g., through the RPE 30 or Bruch's membrane 40), which could damage the eye 10. In some other embodiments, the second surface 1306 is tapered to facilitate the insertion of the end stopper 1300 through the sclera.

[0049] Figure 14A is an isometric view of yet another exemplary injection needle 1410 that may be used with the injection device 100 described herein. Referring to Figure 14A, the injection needle 1410 is curved. For example, in some embodiments, the injection needle 1410 has a first portion 1417 that extends substantially parallel to the central longitudinal axis 120x of the multi-lumen tube 120, and a second portion 1418 that extends at an angle α1, unlike the first portion 1417. In some embodiments, the angle α1 of the second portion 1418 may be about 45 degrees or less (e.g., about 30 degrees or less or about 10 degrees to about 30 degrees).

[0050] Figure 14B is a vertical cross-sectional view of the injection needle 1410 in Figure 14A, showing the injection needle 1410 being inserted into the subretinal space 50. Referring to Figure 14B, the angle α2 between the second portion 1418 of the injection needle 1410 and the surface 32 of the RPE 30 is less than the angle (α1 + α2) between the first portion 1417 and the surface 32. Because of the angle α2 of the second portion 1418, the injection needle 1410 enters the subretinal space 50 at a shallower angle than the angle (α1 + α2) between the first portion 1417 and the surface 32. For example, compare the lower entry angle α2 of the curved injection needle 1410 (Figure 14B) with the relatively higher entry angle of the straight injection needle 1310 (Figure 13B). The curvature of the injection needle 1410 is beneficial because it helps to correctly position the distal end 1414 between the retina 20 and the RPE 30, thereby preventing the injection needle 1410 from being inserted too far into the eye 10 (for example, through the RPE 30 or Bruch's membrane 40).

[0051] Figure 15 is an isometric view of the top of another exemplary stabilizer 1530 that may be used with the injection device 100 described herein. In the embodiment of Figure 15, the stabilizer 1530 is shown in the extended position. In the retracted position, the stabilizer 1530 may be located within the port 118c of the connector piece 116 and / or within the lumen 128c of the multi-lumen tube 120. Referring to Figure 15, the stabilizer 1530 is a wire 1532 formed from a shape memory alloy or a material having high elasticity (e.g., Nitinol). The wire 1532 is coupled to the connector piece 116 of the injection needle 110. In some embodiments shown in Figure 15, the wire 1532 is formed into a pair of wings 1532a, 1532b. In some other embodiments, the wire 1532 may be formed into any preferred shape, including, but not limited to, round, oval, or polygonal. In the retracted position, the wire 1532 may be positioned within the port 118c of the connector piece 116 and / or within the lumen 128c, such that the wings 1532a, 1532b fold substantially parallel to the central longitudinal axis 120x of the multi-lumen tube 120. In some embodiments, a working fluid 145c (e.g., PFCL) is injected from the fluid reservoir 144c (Figure 1A) of the fluid control unit 140 through the lumen 128c to apply pressure and extend the wire 1532 from the lumen 128c. In the extended position, the wings 1532a, 1532b may extend substantially along an axis perpendicular to the central longitudinal axis 120x of the multi-lumen tube 120. In some embodiments, the wire 1532 is held in place primarily by frictional force between the wire 1532 and the surface 22 of the retina 20. In some embodiments, in the extended position, the wire 1532 has a flattened profile. For example, in some embodiments, the width of the wire 1532 measured parallel to the surface 22 of the retina 20 is greater than the height of the wire 1532 measured perpendicular to the surface 22 (e.g., at least twice as much, at least five times as much, or at least ten times as much).

[0052] Figure 16 is an isometric view of the top of yet another exemplary stabilizer 1630 that may be used with the infusion device 100 described herein. In the embodiment of Figure 16, the stabilizer 1630 is shown in the extended position. In the retracted position, the stabilizer 1630 may be located within the port 118c of the connector piece 116 and / or within the lumen 128c of the multi-lumen tube 120. In some embodiments shown in Figure 16, which may be combined with other embodiments disclosed herein but are not limited thereto, the stabilizer 1630 includes a barb 1634 arranged on a structure 1632 (e.g., a balloon, wire, plate, or a combination thereof). The structure 1632 is shown by dashed lines to more clearly illustrate the barb 1634 arranged on its back surface. The barb 1634 is configured to increase friction between the stabilizer 1630 and the surface 22 of the retina 20. In some other embodiments, other friction-inducing elements may be incorporated onto the structure 1632 in addition to or instead of the multiple barbs 1634 (e.g., rough texture, teeth, thorns, or a combination thereof). In some embodiments shown in Figure 16, the structure 1632 includes a pair of wings 1632a, 1632b. In some other embodiments, the structure 1632 may have any preferred shape, including, but not limited to, round, oval, or polygonal. In some embodiments, in the extended position, the structure 1632 has a flattened profile. For example, in some embodiments, the width of the structure 1632 measured parallel to the surface 22 of the retina 20 is greater than the height of the structure 1632 measured perpendicular to the surface 22 (e.g., at least twice as much, at least five times as much, or at least ten times as much).

[0053] Figure 17 is an isometric view of the top of yet another exemplary stabilizer 1730 that may be used with the injection device 100 described herein. In the embodiment of Figure 17, the stabilizer 1730 is shown in the extended position. In the retracted position, the stabilizer 1730 may be located within the port 118c of the connector piece 116 and / or within the lumen 128c of the multi-lumen tube 120. Referring to Figure 17, the stabilizer 1730 includes a plate 1732 and an adhesive 1734. The plate 1732 may be formed from plastic, metal, polymer, nitinol, or a combination thereof. The adhesive 1734 may include an adhesive material based on at least one of fibrin, cyanoacrylate, gelatin, thrombin, polyethylene glycol, albumin, or glutaraldehyde. In some other embodiments, a non-adhesive material, such as a viscoelastic material, may be used for temporary physical bonding. In some other embodiments, the plate 1732 may have a profile that matches the surface 22 of the retina 20 and behave like an adhesive cup, holding the plate 1732 in place. In some other embodiments, a vacuum pressure (e.g., about 1 mmHg (millimeters of mercury) to about 650 mmHg) may be applied to the volume between the plate 1732 and the surface 22 of the retina 20.

[0054] In some embodiments, the adhesive 1734 is pre-applied to the plate 1732 when the plate 1732 is folded inside the connector piece 116 (for example, on the back surface of the plate 1732 facing the surface 22 of the retina 20). In some embodiments shown in Figure 17, when the back surface of the plate 1732 is in contact with the surface 22 of the retina 20, the adhesive 1734 is configured to at least lightly adhere the plate 1732 to the surface 22 of the retina 20. In some embodiments, the adhesive 1734 may increase friction between the plate 1732 and the surface 22 of the retina 20 without fixing the surfaces together. In some other embodiments, the adhesive 1734 is applied via the lumen 128c in combination with the expansion of the plate 1732. In some embodiments shown in Figure 17, the plate 1732 includes a pair of wings 1732a, 1732b. In some other embodiments, the plate 1732 may have any preferred shape, including, but not limited to, round, oval, or polygonal. In some embodiments, in the extended position, the plate 1732 has a flattened profile. For example, in some embodiments, the width of the plate 1732 measured parallel to the surface 22 of the retina 20 is greater than the height of the plate 1732 measured perpendicular to the surface 22 (e.g., at least twice as much, at least five times as much, or at least ten times as much).

[0055] Figure 18 is a schematic diagram of an exemplary guidewire 1800 that may be used with the injection device 100 described herein. In some embodiments, the guidewire 1800 replaces the inserter device 250. The guidewire 1800 is positioned along the outer wall 126o of the multi-lumen tube 120 substantially parallel to the central longitudinal axis 120x. In some embodiments shown in Figure 18, the guidewire 1800 extends to the distal end 122 of the multi-lumen tube 120. In some embodiments, the guidewire 1800 extends at least partially along the length portion of the multi-lumen tube 120, including extending along the portion of the multi-lumen tube 120 that is inserted into the eye 10. In some embodiments, the guidewire 1800 extends from the proximal end 124 to the distal end 122 of the multi-lumen tube 120. The guidewire 1800 is stiffer than the multi-lumen tube 120. The guidewire 1800 is configured to provide axial stiffness in the direction of the central longitudinal axis 120x in order to apply sufficient axial pressure to the injection needle 110 in order to insert the distal end 114 of the injection needle 110 into the subretinal space 50 at a target position on the surface 22 of the retina 20 without using an inserter device 250. The guidewire 1800 has bending stiffness that is less than its axial stiffness to limit the transmission of undesirable bending forces from the outside of the eye 10 to the injection needle 110.

[0056] In some other embodiments where the inserter device 250 is not used, other mechanisms may be used to provide variable stiffness to the multi-lumen tube 120. In some embodiments, for example, the multi-lumen tube 120 may have high stiffness while the distal end 114 of the injection needle 110 is being inserted into the subretinal space 50 (action 404), and low stiffness to detach the injection needle 110 from external forces after the injection needle 110 has been immobilized at a target position on the surface 22 of the retina 20 (action 406) (for example, during at least one of the following: retraction of the cannula 254 (action 408), injection of non-therapeutic solution 145a (action 410), or injection of therapeutic solution 145b (action 412)). In some embodiments, only the portion of the multi-lumen tube 120 inserted into the eye 10 has variable stiffness. In some other embodiments, the entire length of the multi-lumen tube 120 has variable stiffness.

[0057] In some other embodiments, the stiffness of the multi-lumen tube 120 is changed by applying a voltage to it. For example, at least a portion of the multi-lumen tube 120 has lower stiffness when no voltage is applied and higher stiffness when a voltage is applied. In such embodiments, at least a portion of the multi-lumen tube 120 may be formed from a material that undergoes a voltage-induced chemical or physical change in order to impart higher stiffness to the multi-lumen tube 120.

[0058] In some other embodiments, the stiffness of the multi-lumen tube 120 is changed by applying air pressure to it. For example, at least a portion of the multi-lumen tube 120 has lower stiffness when no air pressure is applied and higher stiffness when air pressure is applied. In such embodiments, one or more lumens of the multi-lumen tube 120 may be filled with air pressure to increase their stiffness.

[0059] In some other embodiments, the multi-lumen tube 120 may include multiple structural segments that impart higher rigidity under compression and lower rigidity under tension. Therefore, the multi-lumen tube 120 may have relatively high rigidity when positioned under compression while the distal end 114 of the injection needle 110 is being inserted into the subretinal space 50 (action 404). After the injection needle 110 is immobilized at the target position on the surface 22 of the retina 20 (action 406), the multi-lumen tube 120 may be positioned under tension to induce lower rigidity in order to detach the injection needle 110 from the external force.

[0060] In summary, embodiments of the present disclosure improve the efficacy and safety of subretinal injections for the treatment of eye conditions. In particular, embodiments of the present disclosure provide hands-free and precisely controlled fluid injection to ensure the correct injection volume and dosage, appropriate flow rate into the subretinal space without damaging the retina or RPE, and appropriate needle shear force to help maintain the bioactivity of the various therapeutic agents carried by the injection fluid. Furthermore, embodiments of the present disclosure detach the injection needle from external forces to prevent inadvertent movement of the injection needle that could cause retinal tears. Moreover, embodiments of the present disclosure provide two injection steps, namely the injection of a non-therapeutic solution and a therapeutic solution, without removing the injection needle from the subretinal space, thereby reducing retinal damage caused by reinserting the injection needle.

[0061] The foregoing relates to embodiments of the present disclosure, but other and further embodiments of the present disclosure may be conceived without departing from its basic scope, and the scope thereof is determined by the following claims.

[0062] Exemplary Embodiments Embodiment 1: The apparatus according to claim 1, wherein the injection needle and the multi-lumen tube are configured to be disconnected from external forces after the injection needle is immobilized at a position on the surface of the retina.

[0063] Embodiment 2: The apparatus according to claim 9, wherein the stabilizer includes a nitinol wire, which is extended by applying pressure or fluid thereto, and in the extended position, the nitinol wire has first and second wings that extend substantially along an axis perpendicular to the longitudinal axis of the distal end of the multi-lumen tube.

[0064] Embodiment 3: The apparatus according to claim 9, wherein the stabilizer includes barbs configured to increase friction between the stabilizer and the surface of the retina.

[0065] Embodiment 4: The apparatus according to claim 9, wherein the stabilizer comprises an adhesive and a plate, the adhesive being placed on the surface of the plate, and the adhesive being configured to increase friction between the surface of the plate and the surface of the retina when the surface of the plate is in contact with the surface of the retina.

[0066] Embodiment 5: The method according to claim 15, further comprising detaching the inserter device from the multi-lumen tube after retraction. Furthermore, this disclosure includes the following inventions. The first aspect is, A device for subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of the eye: 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 certain position on the surface of the retina; A multi-lumen tube having a distal end connected to the proximal end of the injection needle and a proximal end connected to a fluid control unit, wherein the multi-lumen tube has a first lumen and a second lumen; A stabilizer configured to prevent the injection needle from moving at a certain position on the surface of the retina; and A fluid control unit comprising a first fluid reservoir containing a non-treatment solution and a second fluid reservoir containing a treatment solution, wherein the fluid control unit is configured to inject the non-treatment solution from the first fluid reservoir into the subretinal space via a first lumen, and the fluid control unit is configured to inject the treatment solution from the second fluid reservoir into the subretinal space via a second lumen. It is a device that includes [this]. The second aspect is, The multi-lumen tube further includes a third lumen, the stabilizer is coupled to the distal end of the third lumen, and the pressure or fluid applied through the third lumen is configured to cause the stabilizer to expand beyond the distal end of the third lumen, thereby positioning the stabilizer on the surface of the retina, in the first embodiment of the apparatus. The third aspect is, The fluid control unit further includes a third fluid reservoir, and the fluid control unit is configured to inject working fluid from the third fluid reservoir through the third lumen to expand the stabilizer, in a second embodiment of the apparatus. The fourth aspect is, The apparatus in the first embodiment further includes an inserter device, wherein the multi-lumen tube is positioned through the inserter device. The fifth aspect is, The inserter device includes a slit extending longitudinally from its proximal end to its distal end, and the inserter device is configured to detach the multi-lumen tube from the multi-lumen tube outside the eye by sliding the multi-lumen tube through the slit, in a fourth embodiment of the apparatus. The sixth aspect is, The inserter device comprises an enclosed bore extending longitudinally from its proximal end to its distal end, and the inserter device is configured to remain coupled to the multi-lumen tube outside the eye, in a fourth embodiment of the apparatus. The seventh aspect is, The fluid control unit further includes a pump configured to drive the flows of the non-treatment solution and the treatment solution, respectively, wherein the pump is at least one of a variable displacement control pump, a syringe pump, a peristaltic pump, a venturi pump, a lever-operated pump, a valve-operated pump, or a combination thereof, according to the first embodiment of the apparatus. The eighth aspect is, The fluid control unit is a device in a first embodiment that can be attached to at least one of a surgical microscope or the patient's forehead. The ninth aspect is, The stabilizer is an apparatus according to the first embodiment, comprising at least one of a balloon, a nitinol wire, a barb, glue, or a combination thereof. The tenth aspect is, The stabilizer includes a balloon, which is expanded by filling it with a perfluorocarbon liquid, and in the expanded position, the balloon has first and second wings that extend substantially along an axis perpendicular to the longitudinal axis of the distal end of the multi-lumen tube, in the apparatus of the ninth embodiment. The eleventh aspect is, A method of subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of the eye: Inserting the distal end of a needle into the subretinal space at a certain position on the surface of the retina, wherein the needle has a proximal end connected to the distal end of a multi-lumen tube, and the multi-lumen tube has a proximal end connected to a fluid control unit; Applying pressure or fluid through the first lumen of the multi-lumen tube to extend the stabilizer beyond the distal end of the first lumen and bring it into contact with the surface of the retina, thereby immobilizing the injection needle at a certain position on the surface of the retina; Injecting a non-therapeutic solution from the fluid control unit to the subretinal space via the second lumen of the multi-lumen tube; and Using the fluid control unit, the therapeutic solution is injected into the subretinal space via the third lumen of the multi-lumen tube. This method includes [something]. The twelfth aspect is, The injection needle and the multi-lumen tube are configured such that the stabilizer is separated from external forces after contacting the surface of the retina, in an eleventh embodiment of the method. The 13th aspect is, The injection of the non-treatment solution and the treatment solution, respectively, is performed hands-free, according to the eleventh embodiment of the method. The 14th aspect is, The stabilizer is coupled to the distal end of the first lumen, and applying the pressure or fluid through the first lumen is a method in an eleventh embodiment, which includes injecting a working fluid from the fluid control unit into the first lumen. The 15th aspect is, The method in the eleventh embodiment further includes the placement of the multi-lumen tube through an inserter device, and the retraction of the inserter device from the eye after the stabilizer has made contact with the surface of the retina, wherein the injection needle and the multi-lumen tube are disconnected from external forces when the inserter device is retracted from the eye.

Claims

1. A device for subretinal injection into the subretinal space between the retina and the retinal pigment epithelium of the eye: 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 certain position on the surface of the retina; A multi-lumen tube having a distal end connected to the proximal end of the injection needle and a proximal end connected to a fluid control unit, the multi-lumen tube having a first lumen and a second lumen; A stabilizer configured to prevent the injection needle from moving at a certain position on the surface of the retina; and A fluid control unit comprising a first fluid reservoir containing a non-treatment solution and a second fluid reservoir containing a treatment solution, wherein the fluid control unit is configured to inject the non-treatment solution from the first fluid reservoir into the subretinal space via a first lumen, and the fluid control unit is configured to inject the treatment solution from the second fluid reservoir into the subretinal space via a second lumen, The stabilizer includes a balloon, which is expanded by filling it with liquid, and in the expanded position, the balloon has first and second wings that extend substantially along an axis perpendicular to the longitudinal axis of the distal end of the multi-lumen tube. The balloon has a flattened profile such that the width of the balloon, measured parallel to the surface of the retina, is at least twice as large as the height of the balloon, measured perpendicular to the surface of the retina. The multi-lumen tube further includes a third lumen, the stabilizer is coupled to the distal end of the third lumen, and a fluid applied through the third lumen is configured to extend the stabilizer beyond the distal end of the third lumen, thereby positioning the stabilizer on the surface of the retina.

2. The apparatus according to claim 1, wherein the fluid control unit further includes a third fluid reservoir, and the fluid control unit is configured to inject working fluid from the third fluid reservoir through the third lumen to expand the stabilizer.

3. The apparatus according to claim 1, wherein the fluid control unit further includes a pump configured to drive the flow of the non-treatment solution and the treatment solution, the pump being at least one of a variable displacement control pump, a syringe pump, a peristaltic pump, a venturi pump, a lever-operated pump, a valve-operated pump, or a combination thereof.

4. The apparatus according to claim 1, wherein the fluid control unit is attachable to at least one of a surgical microscope or the patient's forehead.

5. The apparatus according to claim 1, further comprising an inserter device, wherein the multi-lumen tube is positioned through the inserter device.

6. The apparatus according to claim 5, wherein the inserter device includes a slit extending longitudinally from its proximal end to its distal end, and the inserter device is configured to detach the multi-lumen tube from the multi-lumen tube outside the eye by sliding the multi-lumen tube through the slit.

7. The apparatus according to claim 5, wherein the inserter device includes an enclosed bore extending longitudinally from its proximal end to its distal end, and the inserter device is configured to remain coupled to the multi-lumen tube outside the eye.

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