Therapeutic agent delivery device with advanceable cannula and needle

Abstract

An apparatus (410) for delivering a therapeutic agent to an eye includes a body (440), a cannula (420), a hollow needle (430), a cannula actuation assembly (500), and a needle actuation assembly (550). The cannula extends distally from the body and is sized and configured to be insertable between the choroid and the sclera of a patient's eye. The cannula actuation assembly is operable to actuate the cannula relative to the body. The needle actuation assembly is operable to actuate the needle relative to the cannula. The cannula is insertable through a sclerotomy to position a distal end of the cannula at a posterior region of the eye between the choroid and the sclera. The needle can be advanced through the choroid to deliver the therapeutic agent to a potential space adjacent to a neural retinal and retinal pigment epithelial cell layer, adjacent to a geographic atrophy region.

Description

[0001] This application is a divisional application of international application PCT / US2015 / 049432 entitled “Therapeutic agent delivery device with a propellable cannula and needle”, which entered the Chinese national phase on March 13, 2017, with Chinese application number 201580049287.X and international application date of September 10, 2015.

[0002] priority

[0003] This patent application claims priority to U.S. Provisional Patent Application 62 / 049,135, filed September 11, 2014, entitled “Suprachoroidal Cannula Advancement Injector,” the disclosure of which is incorporated herein by reference.

[0004] Joint Research Statement

[0005] The subject matter disclosed in this patent application was developed or represented by one or more parties to a joint research contract, and the invention protected by the claims was performed or represented by one or more parties to the joint research contract, which was valid on or before the effective filing date of the invention protected by the claims. The invention protected by the claims originates from activities performed within the scope of the joint research contract. The parties to the joint research contract include Ethicon Endo-Surgery, Inc. and Janssen Research & Development, LLC. Background Technology

[0006] The human eye consists of several layers. The white outer layer is the sclera, which surrounds the choroid. The retina lies inside the choroid. The sclera contains collagen and elastic fibers that protect the choroid and retina. The choroid contains the vascular system that supplies oxygen and nutrients to the retina. The retina contains photosensitive tissue, which includes rods and cones. The macula is located at the center of the retina at the back of the eye, normally centered on the axis (i.e., the visual axis) that runs through the center of the lens and cornea. The macula provides central vision, specifically through cone cells.

[0007] Age-related macular degeneration (AMD) is a medical condition that affects the macula, causing people with AMD to experience loss or decline in central vision while retaining some degree of peripheral vision. AMD can be caused by a variety of factors, such as age (also known as "AMD") and genetics. AMD can occur in a "dry" (non-exudative) form, where cellular debris called drusen accumulates between the retina and choroid, leading to the formation of map-like atrophic areas. AMD can also occur in a "wet" (exudative) form, where blood vessels grow from the choroid behind the retina. Although people with AMD may retain some degree of peripheral vision, the loss of central vision can have a significant negative impact on their quality of life. Furthermore, the quality of retained peripheral vision can decline and, in some cases, may even disappear. Therefore, treatment for AMD is desired to prevent or eliminate vision loss caused by it. In some cases, it is desirable to provide such treatment in a highly focused manner, such as by delivering therapeutic substances to the subretinal layer (below the sensory nerve layer of the retina and above the retinal pigment epithelium) immediately adjacent to the map-like atrophic area near the macula. However, because the macula is located at the back of the eye and below the sensitive layer of the retina, it is difficult to access by practical means.

[0008] Although various surgical methods and instruments for treating the eye have been developed and used, it is believed that no one had developed or used the invention described in the appended claims before the inventors. Attached Figure Description

[0009] Although this specification provides specific and explicit claims to such technology, it is believed that such technology will be better understood from certain examples described below in conjunction with the accompanying drawings, wherein similar reference numerals indicate the same elements, and wherein:

[0010] Figure 1 A perspective view of an exemplary device for subretinal administration of a therapeutic agent via a suprachoroidal route is shown.

[0011] Figure 2 It shows Figure 1 A side front view of the instrument;

[0012] Figure 3 It shows Figure 1 Another side view of the device, showing the locking component removed;

[0013] Figure 4 It shows Figure 1 Another side view of the instrument, in which the actuating member is advanced distally to extend the needle distally from the cannula;

[0014] Figure 5 It shows that it can be combined with Figure 1A perspective view of the distal end of an exemplary cannula in an instrument;

[0015] Figure 6 It shows Figure 5 A cross-sectional view of the cannula, wherein the cross-section is along... Figure 5 The line 6-6 was cut off;

[0016] Figure 7 A perspective view of another exemplary alternative device for subretinal administration of a therapeutic agent via a suprachoroidal route is shown;

[0017] Figure 8 A perspective view of an exemplary suture measurement template is shown, which is used in an exemplary method of administering a therapeutic agent via an over-choroidal route;

[0018] Figure 9A A top plan view of the patient's eye is shown, in which the surrounding structures of the eye are fixed and a chandelier is installed;

[0019] Figure 9B It shows Figure 9A Top plan view of the eye, in which Figure 8 The template is set on the eye;

[0020] Figure 9C It shows Figure 9A A top plan view of the eye, with multiple markers set on the eye;

[0021] Figure 9D It shows Figure 9A Top plan view of the eye, with the suture loop attached to the eye;

[0022] Figure 9E It shows Figure 9A A top view of the eye, in which a sclerotomy is being performed;

[0023] Figure 9F It shows Figure 9A Top plan view of the eye, in which Figure 1 The instruments are being inserted between the sclera and choroid of the eye through the scleral incision.

[0024] Figure 9G It shows Figure 9A Top plan view of the eye, in which Figure 1 The instruments are positioned between the sclera and choroid under direct visualization at the back of the eye;

[0025] Figure 9H It shows Figure 9A Top plan view of the eye, in which Figure 1The needle of the instrument is advanced under direct visualization at the back of the eye, thereby pressing against the outer surface of the choroid to make the choroid 'tent-shaped';

[0026] Figure 9I It shows Figure 9A A top view of the eye, in which a needle distributes a leader vacuole under direct visualization at the posterior part of the eye, the needle being located between the sclera and the choroid, and the leader vacuole being located in the subretinal space between the choroid and the retina;

[0027] Figure 9J It shows Figure 9A A top plan view of the eye, in which a needle dispenses the treatment agent into the eye at the back, between the sclera and the choroid;

[0028] Figure 10A It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9A The line was cut from 10A to 10A;

[0029] Figure 10B It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9E The line 10B-10B was cut off;

[0030] Figure 10C It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9F The line was cut at 10C-10C.

[0031] Figure 10D It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9G The line was cut from 10D to 10D;

[0032] Figure 10E It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9H The line was cut from 10E to 10E;

[0033] Figure 10F It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9I The line was cut from 10F to 10F.

[0034] Figure 10G It shows Figure 9A A cross-sectional view of the eye, wherein the cross-section is around... Figure 9J The line was cut from 10G to 10G;

[0035] Figure 11A It shows Figure 9A A detailed cross-sectional view of the eye, which is shown as being in the position of Figure 10E The state shown;

[0036] Figure 11B It shows Figure 9A A detailed cross-sectional view of the eye, which is shown as being in the position of Figure 10F The state shown;

[0037] Figure 11C It shows Figure 9A A detailed cross-sectional view of the eye, which is shown as being in the position of Figure 10G The state shown;

[0038] Figure 12 A perspective view of an exemplary alternative device for subretinal administration of a therapeutic agent via a suprachoroidal route is shown;

[0039] Figure 13 It shows Figure 12 Another perspective view of the instrument, in which part of the main body has been removed;

[0040] Figure 14 It shows Figure 12 An exploded perspective view of the instrument;

[0041] Figure 15 It shows Figure 12 A perspective view of the cannulation sliding component of the instrument;

[0042] Figure 16 It shows Figure 12 A side cross-sectional view of the cannulation slide of the instrument, wherein the cross-section is along... Figure 15 The line was cut from 16-16;

[0043] Figure 17 It shows Figure 12 A front view of the cross-section of the cannulation slide of the instrument, wherein the cross-section is along... Figure 15 The line was cut at 17-17;

[0044] Figure 18 It shows Figure 12 A perspective view of the needle propulsion component of the instrument;

[0045] Figure 19 It shows Figure 18 Another perspective view of the needle-propelling component;

[0046] Figure 20 It shows Figure 12 A perspective view of the cam lock of the instrument;

[0047] Figure 21 It shows Figure 20 Front view of the cam lock;

[0048] Figure 22 Showing around Figure 15 The sliding part of the cannula is set Figure 20 A front cross-sectional view of the cam lock;

[0049] Figure 23A It shows Figure 12 Another perspective view of the instrument, with the cannula and needle in the retracted position;

[0050] Figure 23B It shows Figure 12 Another perspective view of the instrument, in which the cannula is partially advanced and the needle is locked and retracted;

[0051] Figure 23C It shows Figure 12 Another perspective view of the instrument, in which the cannula is fully advanced and the needle is locked and retracted;

[0052] Figure 23D It shows Figure 12 Another perspective view of the instrument, in which the cannula is fully advanced and the needle is unlocked but still retracted;

[0053] Figure 23E It shows Figure 12 Another perspective view of the instrument, with the cannula and needle in the advanced position;

[0054] Figure 24A It shows Figure 12 Another perspective view of the instrument, in which the instrument housing has been removed and the cannula and needle are in the retracted position;

[0055] Figure 24B It shows Figure 12 Another perspective view of the instrument, in which the instrument housing has been removed and the cannula has been partially advanced and the needle has been locked and retracted;

[0056] Figure 24C It shows Figure 12 Another perspective view of the instrument, in which the instrument housing has been removed and the cannula has been fully advanced and the needle has been locked and retracted;

[0057] Figure 24D It shows Figure 12 Another perspective view of the instrument, in which the instrument housing has been removed and the cannula has been fully advanced and the needle has been unlocked but still retracted;

[0058] Figure 24E It shows Figure 12 Another perspective view of the instrument, in which the instrument housing has been removed and the cannula and needle are in the advanced position;

[0059] Figure 25A It shows Figure 12 A front cross-sectional view of the instrument, with the cam lock in the locked position;

[0060] Figure 25B It shows Figure 12 Another front cross-sectional view of the device, in which the needle advance member is in the unlocked position;

[0061] Figure 26A A partial bottom plan view of the cannula slider and needle advance member is shown, with the needle advance member in the locked and retracted position;

[0062] Figure 26B Another portion of the bottom plan view of the cannula slider and needle advance member is shown, with the needle advance member in the unlocked and retracted position;

[0063] Figure 26C A further bottom plan view of the cannula slide and needle advance member is shown, with the needle advance member in the unlocked and advanced positions;

[0064] Figure 27 A perspective view of another exemplary alternative device for subretinal administration of a therapeutic agent via a suprachoroidal route is shown;

[0065] Figure 28 It shows Figure 27 Another perspective view of the instrument, in which part of the main body has been removed;

[0066] Figure 29 It shows Figure 27 An exploded perspective view of the instrument;

[0067] Figure 30 It shows Figure 27 A cross-sectional view of the instrument, wherein the cross-section is along... Figure 27 The line was cut at 30-30mm.

[0068] Figure 31A It shows Figure 27 A side view of the instrument, in which part of the main body has been removed and the cannula and needle are in the retracted position;

[0069] Figure 31B It shows Figure 27 The other side front view of the instrument, with the cannula in the partially advanced position and the needle in the retracted position;

[0070] Figure 31C It shows Figure 27 Another frontal view of the instrument, with the cannula in the fully advanced position and the needle in the retracted position;

[0071] Figure 31D It shows Figure 27The instrument is shown from the side with the cannula fully advanced and the needle in the advanced position.

[0072] Figure 32A A perspective view of another exemplary alternative device for subretinal administration of a therapeutic agent via a suprachoroidal route is shown;

[0073] Figure 32B It shows Figure 32A Another perspective view of the instrument, with the cannula in the advanced position and the needle in the retracted and locked position; and

[0074] Figure 32C It shows Figure 32A Another perspective view of the instrument, with the cannula in the advanced position and the needle in the unlocked and advanced position.

[0075] The accompanying drawings are not intended to be limiting in any way, and various embodiments of the present technology can be implemented in a variety of other ways, including those not necessarily shown in the drawings. The drawings, which are incorporated in and form a part of this specification, illustrate several aspects of the present technology and, together with the specification, serve to explain the principles of the present technology; however, it should be understood that this technology is not limited to the precise arrangements shown. Detailed Implementation

[0076] The examples of the present technology described below should not be construed as limiting the scope of the present technology. Other examples, features, aspects, embodiments, and advantages of the present technology will become apparent to those skilled in the art from the following description, which is given by way of example and is one of the best modes contemplated for implementing the present technology. As will be appreciated, the technology described herein can include other different and obvious aspects without departing from the present invention. Therefore, the drawings and description should be considered substantially illustrative and not restrictive.

[0077] It should also be understood that any one or more of the teachings, expressions, embodiments, examples, etc., described herein may be combined with any one or more of the other teachings, expressions, embodiments, examples, etc., described herein. Therefore, the following teachings, expressions, embodiments, examples, etc., should not be considered in isolation from each other. Various suitable ways in which the teachings herein can be combined will be apparent to those skilled in the art, referring to the teachings herein. Such modifications and variations are intended to be included within the scope of the claims.

[0078] For clarity of this disclosure, the terms “proximal” and “distal” are defined herein with respect to a surgeon or other operator holding a surgical instrument with a distal surgical end effector. The term “proximal” refers to a position where the element is closer to the surgeon or other operator, and the term “distal” refers to a position where the element is closer to the surgical end effector of the surgical instrument and further away from the surgeon or other operator.

[0079] I. An exemplary device having a slider joint motion feature structure

[0080] Figure 1-4 An exemplary device 10 is shown, configured for use in the subretinal administration of a therapeutic agent to a patient's eye via a suprachoroidal route. Device 10 includes a flexible cannula 20, a body 40, and a slidable actuation assembly 60. The cannula 20 extends distally from the body 40 and has a substantially rectangular cross-section. The cannula 20 is generally configured to support a needle 30 that slides within the cannula 20, as will be described in more detail below.

[0081] In this example, the cannula 20 comprises a flexible material, such as polyether block amide (PEBA), which can be manufactured under the trade name PEBAX. Of course, any other suitable material or combination of materials can be used. Additionally, in this example, the cannula 20 has a cross-sectional profile of approximately 2.0 mm × 0.8 mm and a length of approximately 80 mm. Alternatively, any other suitable dimensions can be used.

[0082] As will be described in more detail below, the cannula 20 is sufficiently flexible to conform to the specific structure and contour of the patient's eye, yet possesses sufficient column strength to allow it to advance between the sclera and choroid of the patient's eye without buckling. Several factors can contribute to the appropriate flexibility of the cannula 20. For example, the hardness of the material used to construct the cannula 20 at least partially characterizes its flexibility. By way of example only, the material used to form the cannula 20 may have a Shore hardness of about 27D, about 33D, about 42D, about 46D, or any other suitable Shore hardness. It should be understood that the Shore hardness may be in the range of about 27D to about 46D; or more specifically, in the range of about 33D to about 46D; or more specifically, in the range of about 40D to about 45D. The specific cross-sectional shape of the cannula 20 can also at least partially characterize its flexibility. Additionally, the stiffness of the needle 30 disposed within the cannula 20 can at least partially characterize its flexibility.

[0083] In this example, the flexibility of the cannula 20 can be quantified by calculating its bending stiffness. Bending stiffness is calculated as the product of the elastic modulus and the area moment of inertia. By way of example only, one exemplary material that could be used to form the cannula 20 could have a Shore hardness of D27 and a strength of 1.2 × 10⁻⁶. 7 N / m2 The elastic modulus (E) and 5.52 × 10 -14 m 4 The area moment of inertia (I) x This provides 0.7 × 10 -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may have a Shore hardness of D33 and a strength of 2.1 × 10⁻⁶. 7 N / m 2 The elastic modulus (E) and 5.52 × 10 -14 m 4 The area moment of inertia (I) x This provides 1.2 × 10 -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may have a Shore hardness of D42 and a strength of 7.7 × 10⁻⁶. 7 N / m 2 The elastic modulus (E) and 5.52 × 10 -14 m 4 The area moment of inertia (I) x This provides 4.3 × 10 -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may have a Shore hardness of D46 and a strength of 17.0 × 10⁻⁶. 7 N / m 2 The elastic modulus (E) and 5.52 × 10 -14 m 4 The area moment of inertia (I) x This provides 9.4 × 10 -6 Nm 2 The calculated bending stiffness around the x-axis. Therefore, by way of example only, the bending stiffness of the tube 20 can be located at approximately 0.7 × 10⁻⁶. -6 Nm 2 From approximately 9.4 × 10 -6 Nm 2 Within that range; or more specifically, approximately 1.2 × 10⁻⁶. -6 Nm 2 From approximately 9.4 × 10 -6 Nm 2 Within the range; or more specifically, approximately 2.0 × 10⁻⁶. -6 Nm 2 To approximately 7.5 × 10 -6 Nm 2 Within that range; or more specifically, approximately 2.0 × 10⁻⁶. -6 Nm 2 From approximately 6.0 × 10-6 Nm 2 Within that range; or more specifically, approximately 3.0 × 10⁻⁶. - 6 Nm 2 To approximately 5.0 × 10 -6 Nm 2 Within that range; or more specifically, approximately 4.0 × 10⁻⁶. -6 Nm 2 To approximately 5.0 × 10 -6 Nm 2 Within the range.

[0084] In this example, the flexibility of the cannula 20 can also be quantified by the following formula:

[0085] (1) δ=(FL^3) / 48EI

[0086] In the above equation, the bending stiffness (EI) is experimentally calculated by deflecting the cannula 20 with a fixed span (L) by a predetermined distance to produce a predetermined amount of deflection (δ). The amount of force (F) required for such deflection can then be recorded. For example, when using this method, the cannula 20 may have a span of 0.06 m and be deflected by a given distance. By way of example only, an exemplary material that can be used to form the cannula 20 may require a force of 0.0188 N to achieve a deflection of 0.0155 m, thereby providing 5.5 × 10⁻⁶ N. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0205 N to achieve a deflection of 0.0135 m, thereby providing 6.8 × 10⁻⁶. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0199 N to achieve a deflection of 0.0099 m, thus providing 9.1 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0241 N to achieve a deflection of 0.0061 m, thereby providing 1.8 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0190 N to achieve a deflection of 0.0081 m, thereby providing 1.0 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0215 N to achieve a deflection of 0.0114 m, thereby providing 8.4 × 10⁻⁶ m. -6Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0193 N to achieve a deflection of 0.0170 m, thereby providing 5.1 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0224 N to achieve a deflection of 0.0152 m, thereby providing 6.6 × 10⁻⁶. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0183 N to achieve a deflection of 0.0119 m, thereby providing 6.9 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0233 N to achieve a deflection of 0.0147 m, thereby providing 7.1 × 10⁻⁶ m. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0192 N to achieve a deflection of 0.0122, thereby providing 7.1 × 10⁻⁶. -6 Nm 2 The calculated bending stiffness around the x-axis. Another exemplary material that can be used to form the cannula 20 may require a force of 0.0201 N to achieve a flexural stiffness of 0.0201 N, thereby providing 4.5 × 10⁻⁶ N. -6 Nm 2 The calculated bending stiffness about the x-axis. Therefore, by way of example only, the bending stiffness of the tube 20 can be approximately 1.0 × 10⁻⁶. -6 Nm 2 From approximately 9.1 × 10 -6 Nm 2 Within this range. It should be understood that in other examples, the bending stiffness of the cannula can be approximately 0.7 × 10⁻⁶. -6 Nm 2 From approximately 11.1 × 10 -6 Nm 2 Within that range; or more specifically, approximately 2.0 × 10⁻⁶. -6 Nm 2 From approximately 6.0 × 10 -6 Nm 2 Within the range.

[0087] The needle 30 may have a different bending stiffness than the cannula 20. By way of example only, the needle 30 may be formed of a nitinol material having a bending stiffness of 7.9 × 10⁻⁶. 10 N / m 2The elastic modulus (E) and 2.12 × 10 -17 m 4 The area moment of inertia (I) x This provides 1.7 × 10 -6 Nm 2 The calculated bending stiffness around the x-axis. To further illustrate, the bending stiffness of needle 30 can be approximately 0.5 × 10⁻⁶. -6 Nm 2 To approximately 2.5 × 10 -6 Nm 2 Within the range; or more specifically, within approximately 0.75 × 10⁻⁶. -6 Nm 2 To approximately 2.0 × 10 -6 Nm 2 Within that range; or more specifically, within approximately 1.25 × 10⁻⁶. -6 Nm 2 From approximately 1.75 × 10 -6 Nm 2 Within the range.

[0088] As in Figure 5 and Figure 6 As can be seen, the cannula 20 includes two side lumens 22 extending longitudinally through the cannula 20 and terminating at a distal end 26 of an abductive bevel and a single central lumen 24. Lateral openings 28 of the bevel are located proximal to the distal end 26 of the bevel. The side lumens 22 contribute to the flexibility of the cannula 20. Although lumens 22, 24 are shown as openings at the distal end 26 of the bevel, it should be understood that in some examples, the side lumens 22, 24 may optionally be closed at the distal end 26 of the bevel. As will be described in more detail below, the central lumen 24 is configured to receive the needle 30 and the needle guide 80. In some configurations, an optical fiber (not shown) is also disposed transversely to the needle 30 within the central lumen 24. Such optical fibers may be used to provide illumination and / or optical feedback.

[0089] The distal end 26 of the bevel is generally inclined to provide separation between the sclera and choroidal layers, allowing the cannula 20 to be advanced between these layers without trauma to the sclera or choroid. In this example, the distal end 26 of the bevel is inclined at an angle of about 15° relative to the longitudinal axis of the cannula 20 in this example. In other examples, the bevel angle of the distal end 26 may range from about 5° to about 50°; or more specifically from about 5° to about 40°; or more specifically from about 10° to about 30°; or more specifically from about 10° to about 20°. Of course, the distal end 26 may have any other suitable configuration. By way of example only, the distal end 26 may be a rounded end rather than a beveled end.

[0090] A needle guide 80 is disposed within the lumen 24 such that its distal end abuts a beveled lateral opening 28. The needle guide 80 is generally configured to guide the needle 30 upward through the beveled opening 28 of the cannula 20 along an outlet axis (EA) oriented obliquely relative to the longitudinal axis (LA) of the cannula 20. The needle guide 80 may be formed of plastic, stainless steel, and / or any other suitable biocompatible material. The needle guide 80 is shaped to be insertable into the central lumen 24. In this example, the needle guide 80 is secured within the central lumen 24 by pressure or interference fit; however, in other examples, adhesives and / or mechanical locking mechanisms may be used to secure the needle guide 80.

[0091] As in Figure 6 As best seen, the needle guide 80 defines an internal lumen 84 configured to slidably receive the needle 30. Specifically, the internal lumen 84 includes a generally straight proximal portion 86 and a curved distal portion 88. The straight proximal portion 86 corresponds to the longitudinal axis (LA) of the cannula 20, while the curved distal portion 88 curves upward away from the longitudinal axis of the cannula 20. In this example, the curved distal portion 88 is curved to guide the needle 30 along an exit axis (EA) that extends distally from the cannula 20 at an angle of about 7° to about 9° relative to the longitudinal axis (LA) of the cannula 20. It should be understood that such an angle can facilitate flexing of the needle 30 in a certain direction to ensure that the needle penetrates into the choroid 306 and minimize the possibility that the needle 30 passes through the suprachoroidal space below the choroid 306 (in contrast to penetrating the choroid 306) and the possibility of retinal perforation. By way of further example only, bending the distal portion 88 can force the needle 30 away from the cannula 20 along the exit axis (EA), which is oriented at an angle of about 5° to about 30° relative to the longitudinal axis (LA) of the cannula 20; or more specifically, at an angle of about 5° to about 20° relative to the longitudinal axis (LA) of the cannula 20; or more specifically, at an angle of about 5° to about 10° relative to the longitudinal axis (LA) of the cannula 20.

[0092] The needle 30 is in the form of an internal cannula having a pointed distal end 32 and defining an internal lumen 34. In this example, the distal end 32 has a lancet configuration. In some other forms, the distal end 32 has a tri-bevel configuration or any other configuration, as described in U.S. Patent Application 14 / 619,256, filed February 11, 2015, entitled “Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent,” the disclosure of which is incorporated herein by reference. Other suitable forms of the distal end 32 will be apparent to those skilled in the art from the teachings herein. The needle 30 of this example comprises a stainless steel hypodermal injection needle sized to deliver a therapeutic agent while being small enough to minimize collateral wounds as the needle 30 penetrates the tissue structures of the patient's eye, as will be described in more detail below. By way of example only, the needle 30 may be a 35 gauge with an inner diameter of 100 μm, but other suitable sizes may be used. For example, the outer diameter of needle 30 may be in the range of 27 to 45; or more specifically, in the range of 30 to 42; or more specifically, in the range of 32 to 39. As another example only, the inner diameter of needle 30 may be in the range of about 50 μm to about 200 μm; or more specifically, in the range of about 50 μm to about 150 μm; or more specifically, in the range of about 75 μm to about 125 μm.

[0093] Re-reference Figure 1 and Figure 2 The body 40 is typically shaped as an elongated rectangle with a curved distal end. The specific shape of the body 40 shown is configured to be grasped by an operator. Alternatively, the body 40 may be mounted on a support device or robotic arm to facilitate positioning of the device 10, as described in U.S. Patent Application 14 / 619,256, filed February 11, 2015, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent," the disclosure of which is incorporated herein by reference.

[0094] The actuation assembly 60 includes an actuating member 62 and a locking member 66. The locking member 66 is removably attached to the body engagement portion 50 between the body 40 and the actuating member 62. As will be described in more detail below, the locking member 66 fills the space between the body 40 and the actuating member 62 to prevent the actuating member 62 from advancing distally relative to the body 40. However, the locking member 66 can be removed to selectively allow the actuating member 62 to advance distally relative to the body 40.

[0095] Figures 2-4 An exemplary actuation of the device 10 is shown. Specifically, as in Figure 2 As can be seen, the needle 30 initially retracts into the cannula 20, and the locking member 66 is positioned between the body 40 and the actuating member 62, thereby preventing the actuating member 62 from advancing. With the instrument 10 in this configuration, the cannula 20 can be positioned inside the patient's eye, as will be described in more detail below.

[0096] Once the cannula 20 is positioned within the patient's eye, the operator can expect to advance the needle 30 relative to the cannula 20. To advance the needle 30, the operator can first remove the locking member 66 by pulling it away from the instrument 10, as in Figure 3 As can be seen in the image. Once the locking member 66 is removed, the actuating member 62 can move or translate relative to the body 40 to advance the needle 30 relative to the cannula 20, as described in U.S. Patent Application 14 / 619,256, filed February 11, 2015, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent," the disclosure of which is incorporated herein by reference. The actuating member 62 of this example is configured only to translate the needle 30 and not to rotate it. In other examples, rotation of the needle 30 is expected. Therefore, alternative examples may include feature structures in the actuating member 62 for rotating and translating the needle 30.

[0097] In this example, such as Figure 4As shown, advancing the actuating member 62 to contact the body 40 corresponds to advancing the needle 30 to a predetermined penetration distance relative to the cannula 20 to reach the patient's eye. In other words, the device 10 is configured such that the operator only needs to advance the actuating member 62 to contact the body 40 to properly position the needle 30 within the patient's eye. In some examples, the predetermined advance distance of the needle 30 relative to the cannula 20 is between about 0.25 mm and about 10 mm; or more specifically, in the range of about 0.1 mm to about 10 mm; or more specifically, in the range of about 2 mm to about 6 mm; or more specifically, about 4 mm. In other examples, the contact between the actuating member 62 and the body 40 may not be particularly significant except for the maximum advance of the needle 30 relative to the cannula 20. Instead, the device 10 may be equipped with certain tactile feedback features to indicate to the operator when the needle 30 has advanced to certain predetermined distances relative to the cannula 20. Therefore, the operator can determine the desired depth of needle 30 penetration into the patient's eye based on direct visualization of markings on the instrument and / or on tactile feedback from instrument 10. Of course, such tactile feedback features can be combined with this example, as will be apparent to those skilled in the art from the teachings herein.

[0098] (II) Exemplary alternative instruments and features

[0099] In some examples, it may be desirable to modify certain components or features of the instruments described herein. For example, it may be desirable to use an instrument similar to instrument 10 with an alternative mechanism for actuating the needle 30. However, in other examples, it may be desirable to use an instrument similar to instrument 10 equipped with different geometries for the cannula 20 or needle 30. Instruments having the variations described above may be advantageous for use in different surgical procedures or surgical procedures similar to those discussed above, to engage tissue structures with different physical properties. Although variations of certain examples have been described herein, it should be understood that the instruments described herein may include any other alternative features that will be apparent to those skilled in the art from the teachings herein.

[0100] Figure 7An exemplary alternative device 2010 similar to device 10 described above is shown. Although certain structural features and operability of device 2010 are described below, it should be understood that, in addition to or instead of what is described below, device 2010 may be constructed and / or operated according to any teachings of U.S. Patent Application 14 / 619,256, filed February 11, 2015, entitled “Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent,” the disclosure of which is incorporated herein by reference. Like device 10, the device 2010 of this example can generally be used in the procedures described herein to deliver therapeutic fluid across the choroid to a patient's eye. Therefore, it should be understood that device 2010 can be readily used in place of device 10 to perform the medical procedures described herein. Like device 10, the device 2010 of this example includes a cannula 2020, a body 2040, and an actuation assembly 2100. The cannula 2020 includes a nitinol needle extending through it and is substantially the same as the cannula 20 described above. In this example, the cannula 2020 and the needle are substantially the same as the cannula 20 and needle 30 described above.

[0101] The main difference between instrument 10 and instrument 2010 is that the actuation assembly 2100 of instrument 2010 is rotatable rather than slidable. Additionally, instrument 2010 includes a valve assembly (not shown) operable to change the fluid state of the needle. The actuation assembly 2100 is generally operable to longitudinally translate the valve assembly by rotation of the knob member 2110, thereby longitudinally translating the needle relative to the cannula 2020.

[0102] When the actuation assembly 2100 is in the proximal position, the operator can rotate the knob member 2110 in either a counterclockwise or clockwise direction. If the knob member 2110 is rotated counterclockwise, the rotating member 2110 will only rotate freely. To initiate the advance of the actuation assembly 2100, valve assembly, and needle, the operator can rotate the knob member 2110 clockwise. Clockwise rotation of the knob member 2110 will be used to translate the knob member 2110 distally and will also be used to translate the valve assembly and needle distally. The operator can continue clockwise rotation of the knob member 2110 to drive the needle away from the distal end of the cannula 2020. Once the needle has been advanced to its distalst position relative to the distal end of the cannula 2020, further clockwise rotation of the knob member 2110 will only result in free rotation of the knob member 2110 due to slippage of the clutch feature integrated into the actuation assembly 2100. With the needle in the distal position, the operator can actuate the valve assembly to allow delivery of the therapeutic agent via the needle, as described in more detail below.

[0103] After delivery of the therapeutic agent, the operator may subsequently wish to retract the needle. Counterclockwise rotation of the knob member 2110 will cause the actuation assembly 2100, valve assembly, and needle to translate proximally relative to the body 2040. It should be understood that when the actuation assembly 2100 is rotated to actuate the valve assembly and needle, the valve assembly and needle remain substantially rotationally fixed relative to the body 2040. It should also be understood that although the rotating member 2110 in this example is described as manually rotated, the rotating member 2110 may be rotated via a motor and / or some other power source. Therefore, it should be understood that the translation of the needle may be mechanically / electrically driven via a servo motor. The actuation of the servo motor may be controlled by a servo controller, as will be described in more detail below. Such a servo controller may be manually operated. In addition or alternatively, such a servo controller may be operated via a computer that takes action based on feedback from the device 2010 or any other component described herein.

[0104] (III) Exemplary suture measurement template

[0105] Figure 8 An exemplary suture measurement template 210 is shown for use in a subretinal delivery process of a therapeutic agent via a suprachoroidal route, as will be described in more detail below. Generally, template 210 is configured to press against a patient's eye to imprint a specific pigment pattern onto the patient's eye. It should be understood that references to pressing template 210 against a patient's eye herein may include, but are not limited to, pressing template 210 directly against the surface of sclera 304 (e.g., after the conjunctiva has been removed or otherwise displaced). Template 210 includes a rigid body 220 and a rigid axis 240. As will be described in more detail below, body 220 is generally contoured to correspond to the curvature of the patient's eye, such that body 220 can be pressed or placed onto at least a portion of the patient's eye. Body 220 includes an upper guide portion 222 and a plurality of projections 230 extending distally from the ocular surface 224 of body 220.

[0106] The upper guide portion 222 is generally semi-circular in shape and is located at the top of the main body 220. The semi-circular shape of the upper guide portion 222 has a radius corresponding to the curvature of the limbus of the patient's eye. In other words, the upper guide portion 222 bends proximally along a first radius corresponding to the radius of curvature of the patient's eyeball; and bends downward (towards the longitudinal axis of axis 240) along a second radius corresponding to the radius of curvature of the limbus of the patient's eye. As will be described in more detail below, the upper guide portion 222 can be used to correctly position the template 210 relative to the limbus of the patient's eye. Therefore, any pigment that can be deposited onto the patient's eye by the template can be positioned relative to the limbus of the patient's eye.

[0107] The protrusions 230 are spaced apart from the upper guide portion 222 by a predetermined distance. Specifically, the protrusions 230 form a pattern that corresponds to relevant markings used during the method described below. The protrusions 230 in this example include four suture loop protrusions 230a-230h and two sclerotomy protrusions 230i, 230j. The suture loop protrusions 230a-320h and the sclerotomy protrusions 230i, 230j extend outward from the body 220 by an equal distance, such that the protrusions 230 collectively maintain the curvature defined by the body 220. In other words, the ends of the protrusions 230a-230j are all positioned along a curved plane defined by a radius of curvature complementary to the radius of curvature of the patient's eyeball. The ends of the protrusions 230a-230j are rounded and non-invasive, allowing them to press against the eye without damaging the sclera or other parts of the patient's eye.

[0108] A shaft 240 extends proximally from the body 220. The shaft 240 is configured to allow an operator to grasp the template 210 and manipulate the body 220. In this example, the shaft 240 is integral with the body 220. In other examples, the shaft 240 may be selectively attached to the body via a mechanical fastening device, such as a threaded connection or mechanical snap-fit. In some configurations, a kit comprising the shaft 240 and multiple bodies 220 may be provided to the operator. The bodies 220 may have different curvatures to correspond to different eyeballs with different radii of curvature. The operator can thus select an appropriate body 220 from the kit based on the anatomy of a specific patient in front of them; and the operator can then secure the selected body 220 to the shaft 240. Although not shown, it should be understood that the proximal end of the shaft 240 may be fitted with a T-grip, knob, or other gripping features to allow the operator to more easily grasp the shaft 240.

[0109] In exemplary use, the suture loop protrusion 232 and the sclerotomy protrusion 234 each correspond to a specific portion of the method described below. Specifically, before or during the method described below, the operator may coat the protrusion 230 with a biocompatible pigment or ink by pressing the protrusion 230 onto the pigment or ink pad 250, brushing the pigment or ink onto the protrusion 230, or otherwise applying the pigment or ink to the protrusion 230. Of course, some types provide protrusions 230 pre-coated with ink, eliminating the need for the operator to perform the step of applying ink to the protrusion 230 during the procedure described herein. Once the protrusion 230 has received the pigment or ink, the operator may mark the patient eye by pressing the protrusion 230 of the template 210 onto the patient eye, as described in more detail below. Once the template 210 is removed from the patient eye, the pigment from the protrusion remains attached to the eye to mark specific points of interest, as described in more detail below.

[0110] IV. Exemplary method for subretinal delivery of therapeutic agents via a suprachoroidal route

[0111] Figure 9A-11C An exemplary procedure for subretinal delivery of a therapeutic agent via a suprachoroidal route using the device 10 described above is illustrated. However, it should be understood that device 2010 can be readily incorporated into or replaced by device 10 in the procedures described below. The methods described herein, by way of example only, can be used to treat macular degeneration and / or other eye conditions. Although the procedures described herein are discussed in the context of the treatment of age-related macular degeneration, it should be understood that such limitations are not intended or implied. For example, the same techniques described herein can be used to treat retinitis pigmentosa, diabetic retinopathy, and / or other eye conditions in some alternative procedures, which are merely exemplary. Furthermore, it should be understood that the procedures described herein can be used to treat dry or wet age-related macular degeneration.

[0112] As in Figure 9A As can be seen, the procedure begins with the operator using a speculum 312 and / or any other suitable instrument for fixation to secure the tissue surrounding the patient's eye 301 (e.g., the eyelid). Although fixation is described herein with reference to the tissue surrounding the eye 301, it should be understood that the eye 301 itself remains free to move. Once the tissue surrounding the eye 301 has been secured, an eye-light port 314 is inserted into the eye 301 to provide intraocular illumination when viewing the interior of the eye 301 through the pupil. In this example, the eye-light port 314 is positioned in the inferior medial quadrant to allow for superior temporal quadrant sclerotomy. Figure 10A As can be seen, the eye chandelier port 314 is positioned to direct light into the interior of the eye 314 to illuminate at least a portion of the retina (e.g., including at least a portion of the macula). It should be understood that this illumination corresponds to the area of ​​the eye 301 intended for delivery of a therapeutic agent. In this example, only the chandelier port 314 is inserted at this stage, without inserting the optical fiber 315 into the port 314. In some other embodiments, the optical fiber 315 may be inserted into the chandelier port 314 at this stage. In either case, a microscope may be optionally used to visually examine the eye to confirm the correct positioning of the eye chandelier port 314 relative to the target area. In some examples, the target area may be identified by the relative inadequacy of retinal staining. Although Figure 9A A specific location of the eye chandelier port 314 is shown, but it should be understood that the eye chandelier port 314 may have any other location, which will be apparent to those skilled in the art in light of the teachings herein.

[0113] Once the eye chandelier port 314 has been positioned, the conjunctiva can be dissected by cutting into a flap within the conjunctiva and pulling the flap posteriorly, thereby accessing the sclera 304. After this dissection is complete, the exposed surface 305 of the sclera 304 can optionally be bleached using a cauterization tool to minimize bleeding. Once conjunctival dissection is complete, the exposed surface 305 of the sclera 304 can optionally be dried using a WECK-CEL or other suitable absorption device. The eye 301 can then be marked using the template 210 described above. Figure 9B As can be seen, template 210 is positioned to align with the limbus of the eye 301. The operator can apply light force to template 210 to apply pigment to the eye 301. Template 210 is then removed, leaving pigment attached to the exposed surface 305 of the sclera 304, thus providing the operator with visual guidance 320, as shown in [the image / image / description]. Figure 9C As can be seen in the image. The operator can then use the visual guide 320 to attach the suture loop assembly 330 and perform sclerotomy. The visual guide 320 includes a set of suture loop markers 321, 322, 323, 324, 325, 326, 327 and a pair of sclerotomy markers 329.

[0114] Figure 9D The completed suture loop assembly 330 is shown. As will be described in more detail below, the suture loop assembly 330 is generally configured to guide the cannula 20 of the instrument 10 through a sclerotomy and into the eye 301. It can be used to produce Figure 9D The exemplary procedure for the suture loop assembly 330 shown is described in U.S. Patent Application 14 / 619,256, filed February 11, 2015, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent," the disclosure of which is incorporated herein by reference. Once the suture loop assembly 330 has been attached to the eye 301, a sclerotomy can be performed on the eye 301. Figure 9E As can be seen, the eye 301 is incised between sclerotomy markers 329 using a conventional surgical scalpel 313 or other suitable cutting instrument. Although the sclerotomy markers 329 are shown as comprising two separate dots, it should be understood that in other examples, markers 329 may include any other type of marker, such as solid lines, dotted lines, or dashed lines. The sclerotomy procedure creates a small incision 316 through the sclera 304 of the eye 301. Figure 10BIn the best possible view, the scleral incision is performed with particular care to avoid penetration of the choroid 306. Therefore, the scleral incision procedure provides an entry point to the space between the sclera 304 and the choroid 306. Once an incision 316 is prepared in the eye 301, blunt dissection can optionally be performed to locally separate the sclera 304 from the choroid 306. Such dissection can be performed using small, blunt, slender instruments, as will be apparent to those skilled in the art from the teachings herein.

[0115] With the sclerotomy procedure already performed, the operator can insert the cannula 20 of instrument 10 through the incision 316 into the space between the sclera 304 and the choroid 306. For example, in Figure 9F As can be seen, the guiding cannula 20 passes through the guide ring 336 of the suture loop assembly 330 and enters the incision 316. As described above, the guide ring 336 stabilizes the cannula 20. Additionally, the guide ring 336 maintains the cannula 20 in a generally tangential orientation relative to the incision 316. This tangential orientation reduces trauma as the cannula 20 is guided through the incision 316, stabilizing the cannula 20 and preventing damage to surrounding tissue. Once the cannula 20 is inserted into the incision 316 through the guide ring 336, the operator may use clamps or other instruments to further guide the cannula 20 along the non-invasive path. Of course, the use of clamps or other instruments is optional and may be omitted in some examples. Although not shown, it should be understood that in some examples, the cannula 20 may include one or more markers located on its surface to indicate various insertion depths. Although optional, such markers may be advantageous to help identify the correct insertion depth when guiding the cannula 20 along the non-invasive path. For example, the operator can visually observe the position of such markers relative to the guide ring 336 and / or relative to the incision 316 as an indication of the depth at which the cannula 20 is inserted into the eye 301. By way of example only, one such marker may correspond to an insertion depth of approximately 6 mm for the cannula 20.

[0116] Once the cannula 20 is at least partially inserted into the eye 301, the operator can insert the optical fiber 315 into the eye chandelier port 314, but the optical fiber 315 is not yet inserted at this stage. With the eye chandelier port 314 in place and the optical fiber 315 fitted, the operator can activate the eye chandelier port 314 by guiding light through the optical fiber 315 to provide illumination to the eye 301 and thereby visualize the interior of the eye 301. The positioning of the cannula 20 can optionally be further adjusted at this time to ensure correct positioning relative to the map-like atrophic area of ​​the retina 308. In some cases, the operator may wish to rotate the eye 301, for example by pulling on the sutures 334, 339, to guide the pupil of the eye 301 toward the operator in order to optimize visualization of the interior of the eye 301 through the pupil.

[0117] Figure 9G and Figure 10C-10D A cannula 20 is shown guided between the sclera 304 and the choroid 306 to a delivery site for the therapeutic agent. In this example, the delivery site corresponds to the gross posterior region of the eye 301 near a map-like atrophic area of ​​the retina 308. Specifically, in this example, the delivery site is located superior to the macula, in the potential space between the sensory retina and the retinal pigment epithelium. Figure 9G The image shows the eye 301 under direct visualization via a microscope guided through the pupil, with illumination provided by fiber optic cable 315 and port 314. As can be seen, the cannula 20 is at least partially visible through the retina 308 and choroid 306 of the eye 301. Therefore, the operator can access the eye through the cannula 20 from... Figure 10C The indicated position is advanced through eye 301 to Figure 10D The location shown indicates the position for tracking the cannula. This tracking is enhanced in a configuration where visible light is emitted through the distal end of the cannula 20 using optical fiber 34.

[0118] Once intubation 20 has been advanced to the point where... Figure 10D As shown in the delivery section, the operator can advance the needle 30 of the instrument 10, as described above relative to... Figure 3 and Figure 4 As described. (As in...) Figure 9H-9I As seen in 10E and 11A, the needle 30 is advanced relative to the cannula 20, causing the needle 30 to pierce the choroid 306 without penetrating the retina 308. Just before penetrating the choroid 306, the needle 30 can be visualized in direct vision as making the surface of the choroid 306 “tent-like,” as in… Figure 9H As can be seen. In other words, the needle 30 can deform the choroid 306 by pushing it upwards, thereby providing an appearance similar to that of a tent pole deforming the top of a tent. The operator can use this visual phenomenon to identify whether the choroid 306 is about to be punctured and the location of any eventual puncture. The specific amount by which the needle 30 advances sufficient to induce the "tent-like coverage" and subsequently puncture the choroid 306 can be any suitable amount, which can be determined by a variety of factors, such as, but not limited to, general patient anatomy, local patient anatomy, operator preference, and / or other factors. As mentioned above, the exemplary range of needle 30 advancement may be between about 0.25 mm and about 10 mm; or more specifically, between about 2 mm and about 6 mm.

[0119] In this example, after the operator has confirmed that the needle 30 has been correctly advanced by observing the tent-like effect described above, the operator injects a balanced salt solution (BSS) or other similar solution as the needle 30 is advanced relative to the cannula 20. This BSS solution can form a pilot bubble 340 before the needle 30 as it is advanced through the choroid 306. The pilot bubble 340 can be advantageous for two reasons. First, as... Figure 9I , 10F As shown in 11B, the leader bubble 340 provides the operator with another visual indicator to show when the needle 30 is correctly positioned at the delivery site. Secondly, the leader bubble 340 can provide a barrier between the needle 30 and the retina 308 once the needle 30 has penetrated the choroid 306. This barrier can push the retinal wall outward (as shown in...). Figure 10F and 11B (Best viewed from the center), thereby minimizing the risk of retinal perforation as the needle 30 is advanced to the delivery site. In some models, a foot switch is actuated to drive the pilot bubble 340 from the needle 30. Alternatively, other suitable features for driving the pilot bubble 340 from the needle 30 will be apparent to those skilled in the art, taking into account the teachings herein.

[0120] Once the operator observes pilot bubble 340, the operator can stop BSS injection, thus leaving the fluid bag, as in Figure 9I , 10F As can be seen in 11B. Next, the therapeutic agent 341 can be injected via an actuated syringe or other fluid delivery device, as described above with respect to device 10. The specific therapeutic agent 341 delivered can be any suitable therapeutic agent configured to treat an eye condition. Some suitable therapeutic agents, which are merely exemplary, may include, but are not limited to, drugs having small or large molecules, therapeutic cell solutions, certain gene therapy solutions, and / or any other suitable therapeutic agents, as will be apparent to those skilled in the art from the teachings herein. By way of example only, the therapeutic agent 341 may be provided based on at least some of the teachings of U.S. Patent 7,413,734, filed August 19, 2008, entitled “Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells,” the disclosure of which is incorporated herein by reference.

[0121] In this example, the final amount of therapeutic agent 341 delivered to the delivery site is approximately 50 μL, but any other suitable amount may be delivered. In some models, a foot switch is actuated to drive the agent 341 out of the needle 30. Alternatively, other suitable features for driving the agent 341 out of the needle 30 will be apparent to those skilled in the art, referring to the teachings herein. The delivery of the therapeutic agent can be visualized by the expansion of the fluid bag, as in... Figure 9J , 10G As can be seen in 11C. As shown in the figure, when the therapeutic agent 341 is injected into the suprachoroidal space, the therapeutic agent 341 is substantially mixed with the fluid of the lead blister 340.

[0122] Once delivery is complete, the needle 20 can be retracted by sliding the actuation assembly 60 proximally relative to the body 40; and the cannula 30 can then be withdrawn from the eye 301. It should be understood that, due to the size of the needle 20, the site where the needle 20 penetrates the choroid 306 is self-sealing, eliminating the need for additional steps to seal the delivery site through the choroid 306. The suture loop assembly 330 and the chandelier 314 are removable, and the incision 316 in the sclera 304 can be closed using any suitable conventional technique.

[0123] As described above, the process described above can be performed to treat patients with macular degeneration. In some such cases, the therapeutic agent 341 delivered via needle 20 may include cells derived from the postpartum umbilicus and placenta. As described above, and by way of example only, the therapeutic agent 341 may be provided based on at least some of the teachings of U.S. Patent 7,413,734, filed August 19, 2008, entitled “Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells,” the disclosure of which is incorporated herein by reference. Alternatively, needle 20 may be used to deliver any other suitable substance, in addition to or replacing the substances described in or elsewhere in U.S. Patent 7,413,734 and / or herein. By way of example only, the therapeutic agent 341 may include a variety of pharmaceuticals, including but not limited to small molecules, macromolecules, cells, and / or gene therapies. It should also be understood that macular degeneration is only one exemplary example of a condition that can be treated by the process described herein. Other biological conditions that can be addressed using the apparatus and process described herein will be apparent to those skilled in the art.

[0124] V. Exemplary alternative device for subretinal administration of therapeutic agents via the suprachoroidal route

[0125] In some examples, modifications to certain components or features of the instruments described herein may be desired. For example, it may be desirable to use an instrument similar to instrument 10 with an alternative mechanism for actuating the needle 30. Additionally or alternatively, it may be desirable to use an instrument similar to instrument 10 with an additional mechanism for actuating the cannula 20. Instruments having the variations described above may be advantageous for use in different surgical procedures or surgical procedures similar to those discussed above, for engaging tissue structures with different physical properties. Although variations of certain examples have been described herein, it should be understood that the instruments described herein may include any other alternative features that will be apparent to those skilled in the art from the teachings herein.

[0126] A. An exemplary alternative device with a lever actuator

[0127] Figure 12-26C An exemplary alternative device 410 similar to the device 10 described above is shown. It should be understood that device 410 can be readily used in place of device 10 to perform the medical procedures described above. It should also be understood that, unless otherwise stated herein, the device 410 of this example is substantially the same as the device 10 described above. Device 410 includes a cannula 420, a body 440, a cannula guide 442 extending distally from the body 440, a cannula actuation assembly 500, and a needle actuation assembly 550. Unlike the device 10 described above, device 410 is generally configured to selectively advance the cannula 420 and the needle 430 relative to the body 440. The cannula 420 and the needle 430 are substantially the same as the cannula 20 and the needle 30 described above, and therefore will not be described in detail here.

[0128] The body 440 is typically shaped to be grasped by an operator's hand and to enclose multiple components of the cannula actuation assembly 500 and the needle actuation assembly 550. To enable operation of the cannula actuation assembly 500, the body 440 includes two lever channels 444 and two actuation pin channels 445. Similarly, to enable operation of the needle actuation assembly 550, the body 440 includes a single actuator opening 446 defined proximal to the body 440. As will be described in more detail below, channels 444, 445 and opening 446 allow movement of the various components of the cannula actuation assembly 500 and the needle actuation assembly 550, enabling the operator to actuate such components to advance the cannula 420 and / or the needle 430.

[0129] As described above, the intubation guide 442 extends distally from the body 440. Specifically, the intubation guide 442 includes a relatively straight proximal portion 441 and a generally curved distal portion 443. The proximal portion 441 extends distally from the body 440 at an angle relative to the longitudinal axis of the body 440. The distal portion 443 is shown curved away from the longitudinal axis of the body 440 at an increasingly larger angle. It should be understood that the combination of the proximal portion 441 and the distal portion 443 is configured to allow the intubation guide 442 to be oriented at or near the sclerotomy incision 316 or the suture loop assembly 330 described above. Therefore, as will be described in more detail below, the intubation guide 442 is operable to feed the cannula 420 into the appropriate position when the cannula 420 is advanced distally relative to the body 440. Although the cannulation guide 442 shown and described herein has a specific shape, it should be understood that in other examples the cannulation guide 442 may have any other suitable shape, which will be apparent to those skilled in the art in light of the teachings herein.

[0130] The cannula guide 442 typically has a cross-sectional shape corresponding to that of the cannula 420. For example, as described above, the cross-sectional shape of the cannula 420 is generally rectangular. Therefore, the cannula guide 442 may also have a corresponding rectangular cross-sectional shape. The cannula guide 442 is typically hollow, or includes a lumen (not shown) such that the cannula guide 442 is configured to receive the cannula 420 in a slidable manner. In addition to having a shape corresponding to that of the cannula 420, the cannula guide 442 also includes rounded edges such that the cannula guide 420 will not substantially cause external injury.

[0131] In this example, the cannulation guide 442 is constructed of a substantially rigid or semi-rigid material, such that the cannulation guide 442 retains its shape as the cannula 420 is advanced through it. Because the cannulation guide 442 is a non-invasive, rigid or semi-rigid guide, it should be understood that when the instrument is used in the method described above for choroidal delivery of therapeutic agents, the cannulation guide 442 may optionally be placed against the patient's eye or gently pressed to create leverage and help ensure tangential advancement of the cannula 420.

[0132] Figure 13-21 Specifically, the cannulation actuation assembly 500 and the needle actuation assembly 550 are shown. More specifically, Figure 13 The cannulation actuation assembly 500 and needle actuation assembly 550 are fully assembled, with one half of the main body 440 removed. As can be seen, the cannulation actuation assembly 500 includes a cannulation slider 510, a pinion 530, and a cannulation advance lever 540 (in...). Figure 13(The middle portion is removed). Similarly, the needle actuation assembly 550 includes a needle advance member 560 and a cam lock 570 disposed within the cannula slide 510. As will be described in more detail below, the cannula actuation assembly 500 is actuated as follows: the operator presses the cannula advance lever 540 forward, thereby causing the cannula 420 and needle 430 to move distally forward relative to the body 440. The needle 430 is then advanced independently of the cannula 420 as follows: the operator first rotates the needle advance member 560, and then advances the needle advance member 560 distally relative to the body 440.

[0133] Figure 14-17 The various components of the cannula actuation assembly 500 and their relationship to the rest of the instrument 410 are shown in detail. As will be described in more detail below, the cannula actuation assembly 500 is actuated by a cannula advance lever 540, which rotatably drives a pinion 530. The pinion 530 then engages a cannula slider 510 to translate the cannula slider 510 relative to the body 440.

[0134] Figure 15-17 A detailed view of the cannula slider 510 is shown. (See attached image.) Figure 15 As can be seen, the cannula slide 510 includes a cannula channel 512, a rack portion 514, a locking portion 516, and a needle advance member receiving portion 526. The cannula channel 512 is configured to receive the cannula 420 and is disposed within at least a portion of the rack portion 514. Figure 16 As can be seen, the cannula channel 512 terminates in the needle lumen 519, which extends through the cannula slide 510. The cannula 420 can be securely held within the cannula channel 512 by any suitable means, such as adhesive bonding, welding, mechanical fastening, and / or using any other suitable structure or technique. Additionally, it should be understood that the cannula channel 512 may include additional structural features configured to receive the cannula 420. By way of example only, in some examples, the proximal end of the cannula 420 may include a flange or other similar structure, and the cannula channel 512 may include a corresponding groove to further secure the cannula 420 within the cannula channel 512. Other suitable methods for securing the cannula 420 within the cannula channel 512 will be apparent to those skilled in the art based on the teachings herein.

[0135] The rack portion 514 includes a plurality of teeth 515 spaced apart from each other along a longitudinally extending linear path. The distal regions of the teeth 515 are separated into two laterally spaced regions by a cannula channel 512. The specific dimensions and spacing of the teeth 515 correspond to the teeth 532 of the pinion 530. Therefore, the teeth 515 of the rack portion 514 are configured to mesh with the teeth 532 of the pinion 530 to form a rack and gear mechanism. As will be described in more detail below, this mechanism drives the cannula slider 510 to translate, thereby actuating the cannula 420.

[0136] The locking portion 516 of the cannula slide 510 includes a generally cylindrical body 518 having two longitudinally extending members 520, 522 integrally formed therein. (As in...) Figure 17 As best seen in the image, each longitudinal extension member 520, 522 includes a corresponding internal cam surface 521, 523. As will be described in more detail below, the cam surfaces 521, 523 are configured to selectively engage the cam lock 570 of the needle actuation assembly 550 to lock the cannula slide 510 in a specific longitudinal position relative to the body 440 of the instrument 410.

[0137] The needle actuation member receiving portion 526 is positioned proximal to the longitudinally extending members 520, 522. The needle actuation member receiving portion 526 includes a circular upper receiving channel 528 (preferably seen in…). Figure 15 (in the middle) and rectangular lower receiving channel 529 (best seen in) Figure 16 (Middle). As will be described in more detail below, the upper receiving channel 528 is configured to receive a corresponding elongated cylindrical portion 566 of the needle actuation member 560. Similarly, the lower receiving channel 529 is configured to receive a corresponding locking tab 569 of the needle actuation member 560. Although the receiving channels 528 and 529 are shown to have a specific shape, it should be understood that in other examples, the shape of the receiving channels 528 and 529 may be changed according to the specific geometry of the needle actuation member 560.

[0138] Back Figure 14 The pinion 530, as shown, includes a basic cylindrical body having a plurality of teeth 532 extending outwardly therefrom. The body of the pinion 530 also includes a drilled hole extending through it. This drilled hole is configured to receive a pinion pin 538. As will be described in more detail below, the pinion pin 538 is received within the drilled hole to rotatably connect the pinion 530 to a cannula advance lever 540.

[0139] Intubation propulsion lever 540 is also in Figure 14As shown in the figure. As can be seen, lever 540 includes a gripping portion 542 and two arms 544, 546 remote from the gripping portion 542. Each arm 544, 546 includes a corresponding pin groove 545, 547 configured to receive a pinion pin 538. The pin grooves 545, 547 are elongated, allowing the pinion pin 538 to travel vertically to some extent within each pin groove 545, 547. Each arm 544, 546 also includes a corresponding attachment opening 548, 549 rotatably fixed within the lever channel 444 of the body 440 (see figure). Figure 12 ).

[0140] Figure 14 and Figure 18-22 The needle actuation assembly 550 and its relationship to the rest of the instrument 410 are shown in detail. As will be described in more detail below, the needle actuation assembly 550 is generally configured to translate together with the cannula actuation assembly 500 until the cannula actuation assembly 500 is locked in place by the needle actuation assembly 550, thereby allowing the needle 430 to be advanced relative to the cannula 420.

[0141] As described above, the needle actuation assembly 550 includes a needle advance member 560 and a cam lock 570. A detailed view of the needle advance member 560 is provided below. Figure 18 and Figure 19 As shown in the diagram, the needle propulsion member 560 includes an actuating tab 562 and an elongated cylindrical portion 566 extending therefrom. The actuating tab 562 is tab-shaped and configured for gripping by an operator. Although the actuating tab 562 in this example is shown as tab-shaped, it should be understood that in other examples, the actuating tab 562 may be in any other shape suitable for gripping. The actuating tab 562 also includes a locking tab 569. The locking tab 569 is substantially rectangular and is disposed at the interface between the actuating tab 562 and the elongated cylindrical portion 566. As will be described in more detail below, the locking tab 569 is configured to prevent translation of the needle 430 relative to the cannula 420 when the needle actuation assembly 550 is positioned in the locked position.

[0142] As in Figure 19As best seen in the image, the elongated cylindrical portion 566 includes a pair of elongated protrusions 568, which are in the form of fins, extending outward from the elongated cylindrical portion 566. As will be described in more detail below, the elongated protrusions 568 are configured to slidably engage a corresponding pair of elongated channels 574 defined within the cam lock 570, allowing the elongated cylindrical portion 566 to operate to rotate the cam lock 570 while still translating relative to the cam lock 570. Although the elongated cylindrical portion 566 is shown as a basic cylinder with the elongated protrusions 568 projecting outward from it, similar functionality of the elongated cylindrical portion 566 can be achieved in other embodiments through other configurations. For example, in other embodiments, the elongated protrusions 568 may be omitted. Instead of the elongated protrusions 568, the elongated cylindrical portion 566 may include irregular cross-sectional shapes, such as hexagonal, oval, triangular, etc. Of course, in this configuration, the shape of the cam lock 570 can also be modified accordingly to correspond to the cross-sectional shape of the elongated cylindrical portion 566.

[0143] The elongated cylindrical portion 566 also includes a lumen 567 extending therethrough. The lumen 567 is configured to receive the needle 430. It should be understood that the lumen 567 may extend through the proximal end of the needle actuation member 560, thereby allowing the lumen 567 to receive one or more supply tubes. Therefore, it should be understood that the needle actuation member 560 is configured to function as a needle coupling device, thereby coupling the needle 430 to the needle actuation member 560 and / or one or more supply tubes. In some examples, the needle 430 may be securely fixed to the needle actuation member 560 such that any rotational or translational movement of the needle actuation member 560 can be transmitted to the needle 430. In other examples, the needle 430 may be fixed relative to the needle actuation member 560 solely by translation, such that only the translational movement of the needle actuation member 560 is transmitted to the needle 430, while the needle 430 remains rotated independently of the needle actuation member 560. Referring to the teachings herein, various suitable configurations for attaching the needle 430 to the needle actuation member 560 to achieve the desired functions described herein will be apparent to those skilled in the art.

[0144] Cam lock 570 Figure 20 and Figure 21 As best seen in the image. As can be seen, the cam lock 570 includes an elongated structure with a generally elliptical cross-section. The cam lock 570 also defines a lumen 572 extending through it. The lumen 570 is generally circular and has a pair of elongated channels 574 defined by the cam lock 570 on opposite sides of the lumen 572. Figure 22As can be seen and described above, the lumen 572 and channel 574 are configured to slidably receive the elongated cylindrical portion 566 and the elongated protrusion 568 of the needle advance member 560. Therefore, it should be understood that when the operator rotates the needle advance member 560 via the actuating tab 562, the cam lock 570 will correspondingly rotate with the elongated cylindrical portion 566. However, when the needle advance member 560 translates relative to the instrument 410, the cam lock 570 can remain stationary relative to the needle advance member 560.

[0145] Figure 23A-26C An exemplary operating mode using device 410 is shown. Specifically, device 410 is used in... Figure 23A and Figure 24A The state shown begins. As can be seen, both the cannula actuation member 500 and the needle actuation assembly 550 can initially be in a retracted proximal position relative to the body 440. In this position, the cannula advance lever 540 retracts proximally relative to the body 440. Correspondingly, the cannula slider 510 and the pinion 530 are positioned proximally within the body 440. Because the cannula 420 is securely fixed to the cannula slider 510, the cannula 420 is similarly positioned proximally relative to the body 440, such that the cannula 420 is positioned within the cannula guide 442. In this position, the needle 430 is also in a proximal position, such that the distal end of the needle 430 is positioned within the cannula 442.

[0146] To initiate the advancement of the cannula 420, the operator can apply force to the cannula advancement lever 540 to cause the cannula advancement lever 540 to pivot distally relative to the body 440, such as... Figure 23B and Figure 24B As can be seen, because the pinion 530 is rotatably attached to the cannula advance lever 540 via the pinion pin 538, the advancement of the cannula advance lever 540 will cause the pinion 530 to advance accordingly along a linear path. When the pinion 530 moves linearly forward, the teeth 532 of the pinion 530 will engage the teeth 515 of the cannula slide member 510. In addition, the teeth 532 of the pinion 530 will also engage the corresponding teeth 449 that are integral with the main body 440. Therefore, the linear movement of the pinion 530 will cause the pinion 530 to rotate clockwise through the engagement between the teeth 532 of the pinion 530 and the teeth 449 of the main body 440. Then the clockwise rotation of the pinion 530 will cause the cannula slide member 510 to translate distally through the engagement between the teeth 532 of the pinion 530 and the teeth 515 of the main body 510. Because the cannula 420 is securely fixed to the cannula slider 510, the advancement of the cannula slider 510 will cause a corresponding advancement of the cannula 420. When the cannula slider 510 is advanced, due to the friction between the multiple parts of the needle advancement assembly 550 and the cannula slider 510, the needle advancement assembly 550 may also be accidentally advanced together with the cannula slider 510.

[0147] Figure 24C and Figure 25B An instrument 410 with a cannula 420 in the fully advanced position is shown. As can be seen, in the fully advanced position, the cannula slide 510 has been fully advanced relative to the body 440 by the operator's fully distal pivoting of the cannula advance lever 540 via the pinion 530. Although the cannula 420 has been fully advanced distally, it should be understood that the needle 430 remains within the cannula 420 in this position. Specifically, the needle 430 is held within the cannula 420 by the locking tab 569 of the needle advance member 560. As will be described in more detail below, the locking tab 569 of the needle advance member 560 prevents the needle advance member 560 from advancing relative to the cannula slide 510 until the operator rotates the needle advance member 560 so that the locking tab 569 can engage with the lower receiving channel 529 of the cannula slide 510.

[0148] Once the cannula 420 has been fully advanced distally, the operator can initiate the process of advancing the needle 430. (As...) Figure 23C , Figure 24C , Figure 25A and Figure 26A As can be seen, the needle advance component 560 is initially positioned relative to the main body 440 by a rotational angle. To initiate the advance of the needle 430, the operator can rotate component 560 counterclockwise to advance the needle. Figure 23D , Figure 24D , Figure 25B and Figure 26B The vertical position. When the needle advance member 560 rotates to the vertical position, the cannula slide 510 locks in position relative to the body 440. Specifically, as Figure 25B As is best seen, when the rotating needle advance member 560, the cam lock 570 rotates. As the cam lock 570 rotates, its elliptical configuration engages the cam surfaces 521, 523 of the cannula slide 510, maintaining the position of the cannula slide 510 relative to the cam lock 570. The cam lock 570 further engages a pair of locking protrusions 447, 448 that are integral with the interior of the body 440. The locking protrusions 447, 448 engage the cam lock 570, fixing the position of the cam lock 570 longitudinally relative to the body 440, thereby locking the cannula slide 510.

[0149] Rotating the needle advance member 560 relative to the vertical position also aligns the locking tab 569 of the needle advance member 560 with the lower receiving channel 529 of the cannula slide member 510, such as Figure 26B The best visibility is achieved in the middle. After the locking tab 569 and the lower receiving channel 529 are aligned, the operator can then move the needle advance member 560 distally to the center. Figure 23E , Figure 24E and Figure 25BThe distal position is shown. When the needle advance member 560 is advanced distally, the needle 430 moves forward accordingly. Because the cannula slide 510 is now fixed relative to the needle advance member 560, advancement of the needle advance member 560 will cause the needle 430 to move forward relative to the cannula 420, so that the distal end of the needle 430 extends outward from the cannula 420. The therapeutic agent can then be delivered as described above with reference to the method for delivering therapeutic agents on the choroid. It should be understood that when the needle advance member 560 is in the distal position... Figure 26A When in the angular position shown, the locking tab 569 can engage the proximal end of the needle pusher receiving portion 526, thereby preventing the needle pusher 560 from moving distally forward relative to the locking portion 516.

[0150] B. An exemplary alternative device with a pulley actuator

[0151] Figure 27-31D An exemplary alternative device 610 similar to the devices 10,410 described above is shown. It should be understood that device 610 can be readily used in place of device 10,410 to perform the medical procedures described herein. It should be understood that, unless otherwise stated herein, the device 610 of this example is substantially the same as the devices 10,410 described above. Device 610 includes a cannula 620, a body 640, a cannula guide 642 extending distally from the body 640, a cannula actuation assembly 700, and a needle actuation assembly 750. Unlike device 10 described above, device 610 is generally configured to selectively advance the cannula 620 and needle 630 relative to the body 640. The cannula 620 and needle 630 are substantially the same as the cannula 20 and needle 30 described above, and therefore will not be described in detail here.

[0152] The body 640 is typically shaped to be held by an operator's hand and to enclose multiple components of the cannula actuation assembly 700 and the needle actuation assembly 750. To enable operation of the cannula actuation assembly 700, the body 640 includes two wheel supports 644 positioned near the distal end of the body 640. Similarly, to enable operation of the needle actuation assembly 750, the body 640 includes a single actuator opening 646 defined proximally to the body 640. As will be described in more detail below, the supports 644 and the opening 646 allow movement of the various components of the cannula actuation assembly 700 and the needle actuation assembly 750, enabling the operator to actuate such components to advance the cannula 620 and / or the needle 630.

[0153] As described above, the intubation guide 642 extends distally from the body 640. Specifically, the intubation guide 642 includes a relatively straight proximal portion 641 and a generally curved distal portion 643. The proximal portion 641 extends distally from the body 640 at an angle relative to the longitudinal axis of the body 640. The distal portion 643 is shown curved away from the longitudinal axis of the body 640 at an increasingly larger angle. It should be understood that the combination of the proximal portion 641 and the distal portion 643 is configured to allow the intubation guide 642 to be oriented at or near the sclerotomy incision 316 or the suture loop assembly 330 described above. Therefore, as will be described in more detail below, the intubation guide 642 is operable to feed the cannula 620 into the appropriate position when the cannula 620 is advanced distally relative to the instrument. Although the cannulation guide 642 shown and described herein has a specific shape, it should be understood that in other examples the cannulation guide 642 may have any other suitable shape, which will be apparent to those skilled in the art in light of the teachings herein.

[0154] The cannula guide 642 typically has a cross-sectional shape corresponding to that of the cannula 620. For example, as described above, the cannula 620 has a substantially rectangular cross-section. Therefore, the cannula guide 642 may also have a corresponding rectangular cross-sectional shape. The cannula guide 642 is typically hollow, or includes a lumen (not shown) such that the cannula guide 642 is configured to receive the cannula 620 in a slidable manner. In addition to having a shape corresponding to that of the cannula 620, the cannula guide 642 also includes rounded edges such that the cannula guide 620 is substantially free from external injury.

[0155] In this example, the cannulation guide 642 is constructed of a substantially rigid or semi-rigid material, such that the cannulation guide 642 retains its shape as the cannula 620 is advanced through it. Because the cannulation guide 642 is a non-invasive, rigid or semi-rigid guide, it should be understood that when the instrument is used in the method described above for choroidal delivery of therapeutic agents, the cannulation guide 642 may optionally be placed against the patient's eye or gently pressed to create leverage and help ensure tangential advancement of the cannula 620.

[0156] Figures 28-30 Specifically, the cannulation actuation assembly 700 and the needle actuation assembly 750 are shown. Specifically, Figure 28The cannula actuation assembly 700 and needle actuation assembly 750 are fully assembled, with half of the main body 740 removed. As can be seen, the cannula actuation assembly 700 includes a cannula slide 710, a pair of pinions 730, and a cannula advance wheel 740. The needle actuation assembly 750 includes a needle advance member 760 at least partially disposed within the cannula slide 710. As will be described in more detail below, the cannula actuation assembly 700 is actuated as follows: the operator rotates the cannula advance wheel 740 forward (e.g., counterclockwise), causing the cannula 620 and needle 630 to move distally forward relative to the main body 640. The needle 630 is then advanced distally relative to the main body 640, independently of the cannula 620.

[0157] Figure 29 The intubation actuation assembly 700 and its relationship to the rest of the instrument 610 are shown in detail. As will be described in more detail below, the intubation actuation assembly 700 is actuated by an intubation push wheel 740, which rotates to drive a pinion 730. The pinion 730 then engages the intubation slide 710 to translate the intubation slide 710 relative to the body 640.

[0158] Figure 29 and Figure 30 A detailed view of the cannula slider 710 is shown. As can be seen, the cannula slider 710 includes a cannula channel 712, a rack portion 714, an elongated portion 716, and a needle advance member receiving portion 726. The cannula channel 712 is configured to receive a cannula 620 and is disposed within at least a portion of the rack portion 714. Figure 30 As best seen, the cannula channel 712 terminates in the needle lumen 719, which extends through the cannula slide 710. The cannula 620 can be securely held within the cannula channel 712 by any suitable means, such as adhesive bonding, welding, mechanical fastening, etc. Additionally, it should be understood that the cannula channel 712 may include other structural features configured to receive the cannula 620. By way of example only, in some examples, the proximal end of the cannula 620 may include a flange or other similar structure, and the cannula channel 712 may include a corresponding channel to further secure the cannula 620 within the cannula channel 712. Of course, other ways of securing the cannula 620 within the cannula channel 712 will be apparent to those skilled in the art in light of the teachings herein.

[0159] The rack portion 714 includes a plurality of teeth 715 spaced apart from each other along a longitudinally extending linear path. The distal regions of the teeth 715 are separated into two laterally spaced regions by a cannula channel 712. The specific dimensions and spacing of the teeth 715 correspond to the teeth 732 of the pinion 730. Therefore, the teeth 715 of the rack portion 714 are configured to engage with the teeth 732 of each pinion 730 to form a rack and pinion mechanism. As will be described in more detail below, this mechanism drives the cannula slider 710 to translate, thereby actuating the cannula 620.

[0160] The elongated portion 716 of the cannula slide 710 is substantially cylindrical and extends between the rack portion 714 and the needle advance member receiving portion 726. For example... Figure 30 As best seen in the image, the elongated portion 716 defines a borehole 720 extending through the elongated portion 716 and the needle advance member receiving portion 726. The borehole 720 is configured to slidably receive the needle advance member 760, such that the needle advance member 760 can be selectively translated relative to the cannula slider 710. The distal end of the borehole 720 communicates with the needle lumen 719, allowing the needle 630 to extend from the needle advance member 760 through the needle lumen 719.

[0161] The needle propulsion member receiving portion 726 is positioned proximal to the elongated portion 716. The needle propulsion member receiving portion 726 is typically cylindrical, with a radius larger than that of the elongated portion 716. As described above, a bore 720 in the elongated portion 716 extends through the needle propulsion member receiving portion 726. Figure 30 As best seen in the image, the interior of the needle advance member receiving portion 726 includes an upper receiving channel 728. As will be described in more detail below, the upper receiving channel 728 is configured to receive a corresponding tab 769 of the needle advance member 760. The longitudinal length of the upper receiving channel 728 corresponds to the travel distance of the needle advance member 760. As will be understood, when the needle advance member 760 is translated relative to the cannula slide 710 to advance the needle 630, the tab 769 of the needle advance member 760 translates within the upper receiving channel 728. The needle advance member 760 can translate until the tab 769 of the needle advance member 760 reaches the distal end of the upper receiving channel 728. Therefore, it should be understood that the upper receiving channel 728 can act as a brake on the needle advance member 760, preventing the needle 630 from being advanced beyond a certain distance.

[0162] Back Figure 29Each pinion 730, as shown, includes a basic cylindrical body 734 having a plurality of teeth 732 extending outwardly therefrom. The body 734 of each pinion 730 also includes a drilled hole 736 extending through it. The drilled hole 736 is configured to receive a pinion pin 738. As will be described in more detail below, the pinion pin 738 is received within the drilled hole 736 to rotatably connect the pinion 730 to the body 640 of the instrument 610.

[0163] The insertion tube propulsion wheel 740 is also present. Figure 29 As shown in the diagram, wheel 740 includes a gripping portion 742 and two drive portions 744, 746 extending outward from the gripping portion 742. Each drive portion 744, 746 is circular and includes a corresponding set of teeth 745, 747. The teeth 745, 747 are configured to engage with the teeth 732 of each pinion 730, such that the teeth 745, 747 can drive each pinion 730 to rotate together. The cannulation advance wheel 740 also includes a drilled hole 748 extending through it. The drilled hole 748 is configured to receive a wheel pin 749 to rotatably connect wheel 740 to the body 640 of instrument 610.

[0164] Figures 28-30 The needle actuation assembly 750 and its relationship to the rest of the instrument 610 are shown in detail. As will be described in more detail below, the needle actuation assembly 750 is generally configured to translate together with the cannula actuation assembly 700 until the cannula actuation assembly 700 is locked in place by the needle actuation assembly 750, thereby allowing the needle 630 to advance relative to the cannula 620. As described above, the needle actuation assembly 750 includes a needle advance member 760 and two supply tubes 790 extending proximally from the proximal end of the needle advance member 760. As can be seen, the needle advance member 760 includes an actuation portion 762 and an elongated cylindrical portion 766 extending therefrom. The actuation portion 762 is generally cylindrical and configured for operator gripping. Although the actuation portion 762 is shown as cylindrical in this example, it should be understood that in other examples, the actuation portion 762 may be in any other shape suitable for gripping. As will be described in more detail above, the actuating member 762 receives the supply tube 790 so that the supply tube 790 can communicate with the needle 730.

[0165] As in Figure 29As best seen in the image, the elongated cylindrical portion 766 includes a tab 769 extending outwardly from the elongated cylindrical portion 766. As described above, the tab 769 is configured to fit within the upper receiving channel 728 of the cannula slide 710, thereby allowing the needle advance member 760 to slide limitedly relative to the cannula slide 710. It should be understood that "limited sliding" in this context means restricting the movement of the tab 769 in the longitudinal direction by the upper receiving channel 728, allowing the needle advance member 760 to translate a predetermined distance relative to the cannula slide 710. In the lateral or rotational direction, the tab 769 is fixed relative to the upper receiving channel 728, minimizing the lateral or rotational movement of the tab 769 relative to the upper receiving channel 728. In other words, the tab 769 and the upper receiving channel 728 work together to allow the needle advance member 760 to translate a predetermined distance relative to the cannula slide 710; while preventing the needle advance member 760 from rotating relative to the cannula slide 710.

[0166] The elongated cylindrical portion 766 also includes a lumen 770 extending from and at least partially through the distal end of the elongated cylindrical portion 766. The lumen 770 is configured to receive the needle 430, and it should be understood that in some examples, the lumen 770 may include needle retention features such as channels, adhesive ports, etc. Figure 30 As best seen, the lumen 770 extends proximally through the elongated cylindrical portion 766 until it intersects with the conical mixing chamber 772. Specifically, in this example, the needle propulsion member 760 is configured to receive two supply tubes 790. Therefore, the conical mixing chamber 772 is positioned between the supply tubes 790 and the lumen 770 to ensure that fluids exiting from the supply tubes 790 can flow properly and / or be mixed. It should be understood that the mixing chamber 772 is entirely optional and can be omitted in some examples. For example, in some examples, the needle propulsion member 760 may be equipped with a single supply tube 790, thereby reducing the need for the mixing chamber 772. It should also be understood that two or more fluid components do not need to be mixed in the mixing chamber 772, allowing the chamber 772 to simply function as a multi-input manifold for the needle 630. For example, in the medical procedure described above, the chamber 772 may selectively receive a pilot bubble 340 before the therapeutic agent 341.

[0167] The supply tube 790 is connected to the mixing chamber 772 via two lumens 774 and 775 extending proximally from the mixing chamber 772. The lumens 774 and 775 are configured to securely hold the supply tube 790 within the elongated cylindrical portion 766. In some examples, this is achieved through an interference fit between the lumens 774 and 775 and the supply tube 790. In other examples, the supply tube 790 can be securely held by any other suitable means, such as adhesive bonding, mechanical percussion, etc. The lumens 774 and 775 extend proximally within the elongated cylindrical portion 766 until they intersect with the tube bore 776. The tube bore 776 extends through the elongated cylindrical portion 766 and the actuating portion 762 to the proximal end of the needle advance member 760, allowing the supply tube 790 to move freely about the tube bore 776. Although lumens 774 and 775 are shown to extend only partially through the elongated cylindrical portion 766, it should be understood that in other examples, lumens 774 and 775 may extend through the elongated cylindrical portion 766 at the borehole 776.

[0168] Figures 31A-31D An exemplary operating mode using device 610 is shown. Specifically, device 610 is used in... Figure 31A The state shown begins. As can be seen, both the cannula actuation member 700 and the needle actuation assembly 750 can initially be in a retracted proximal position relative to the body 640. In this position, the cannula advance wheel 740 rotates to its farthest counterclockwise position. Correspondingly, the cannula slider 710 has been driven to its nearest position within the body 640. Because the cannula 620 is securely fixed to the cannula slider 710, the cannula 620 is similarly positioned proximal relative to the body 640, such that the cannula 620 is positioned within the cannula guide 642. In this position, the needle 630 is also in a proximal position, such that the distal end of the needle 630 is positioned within the cannula 642.

[0169] To initiate the advancement of the cannula 620, the operator can apply force to the cannula advancement wheel 740, causing the cannula advancement wheel 740 to rotate counterclockwise relative to the main body 640, such as... Figure 31BAs can be seen, because the teeth 732 of the pinion 730 engage with the teeth 745 and 747 of the cannula advance wheel 740, the rotation of the cannula advance wheel 740 will cause the pinion 730 to rotate clockwise accordingly. When the pinion 730 rotates clockwise, the teeth 732 of the pinion 730 will engage the teeth 715 of the cannula slider 710 to translate the cannula slider 710 distally. Therefore, the counterclockwise rotation of the cannula advance wheel 740 will cause the cannula slider 710 to translate distally via the pinion 730. Because the cannula 620 is firmly fixed to the cannula slider 710, the advancement of the cannula slider 710 will cause the cannula 620 to advance accordingly. When the cannula slide 710 is advanced, the needle push assembly 750 is also advanced accordingly due to the engagement between the protrusion 769 of the needle push member 760 and the upper receiving channel 728 of the cannula slide 710.

[0170] Figure 31C An instrument 610 is shown with a cannula 620 in the fully advanced position. As can be seen, in the fully advanced position, the cannula slide 710 has been fully advanced relative to the body 640 by the operator fully rotating the cannula advance wheel 740 via the pinion 730. Although the cannula 620 has been fully advanced distally, it should be understood that in this position, the needle 630 remains within the cannula 620 until the operator applies a force distally to the needle advance member 760 to translate the needle advance member 760 relative to the cannula slide 710.

[0171] Once the cannula 620 has been fully advanced distally, the operator can initiate the process of advancing the needle 630. (As...) Figure 31C As can be seen, the needle advance member 760 is initially positioned such that there is at least some gap between the needle advance member receiving portion 726 of the cannula slide 710 and the actuating portion 762 of the needle advance member 760. Although not shown, it should be understood that in some examples, such gaps can be maintained by a removable member disposed between the needle advance member receiving portion 726 of the cannula slide 710 and the actuating portion 762 of the needle advance member 760. When the instrument 610 is equipped with such a removable member, it is removed before initiating the advance of the needle 630. To initiate the advance of the needle 630 in this example, the operator may grasp the needle advance member 760 and translate the needle advance member 760 relative to the cannula slide until the needle 630 is positioned in the desired position relative to the cannula 620. Alternatively, the operator may translate the needle advance member 760 until the tab 769 of the needle advance member 760 contacts the distal end of the upper receiving channel 728 of the cannula slide 710, thereby preventing further translation of the needle advance member 760 relative to the cannula slide 710. The therapeutic agent can then be delivered as described above with reference to the method for delivering therapeutic agents on the choroid.

[0172] C. Exemplary alternative device with locking clamp.

[0173] Figures 32A-32C An exemplary alternative device 810 similar to the devices 410, 610 described above is shown. It should be understood that device 810 can readily replace devices 10, 410, 610 for use in performing the medical procedures described herein. It should be understood that, unless otherwise stated herein, the device 810 of this example is substantially the same as the devices 10, 410, 610 described above. Device 810 includes a cannula 820 (… Figure 32B The device 810 comprises a main body 840, an insertion guide 842 extending distally from the main body 840, an insertion actuation assembly 900, and a needle actuation assembly 950. Unlike the device 10 described above, the device 810 is generally configured to selectively advance the insertion cannula 820 and the needle 830 relative to the main body 840. Figure 32C The cannula 820 and needle 830 are essentially the same as the cannula 20 and needle 30 described above, so their specific details will not be described here.

[0174] The body 840 is typically shaped to be held by an operator's hand and enclose multiple components of the cannula actuation assembly 900 and the needle actuation assembly 950. To enable operation of the cannula actuation assembly 900, the body 840 includes two wheel supports 844 positioned near the distal end of the body 840. Similarly, to enable operation of the needle actuation assembly 950, the body 840 includes a single actuator opening 846 defined proximally to the body 840. As will be described in more detail below, the supports 844 and the opening 846 allow movement of the various components of the cannula actuation assembly 900 and the needle actuation assembly 850, enabling the operator to actuate such components to advance the cannula 820 and / or the needle 830.

[0175] As described above, the intubation guide 842 extends distally from the body 840. Specifically, the intubation guide 842 includes a relatively straight proximal portion 841 and a generally curved distal portion 843. The proximal portion 841 extends distally from the body 840 at an angle relative to the longitudinal axis of the body 840. The distal portion 843 is shown curved away from the longitudinal axis of the body 840 at an increasingly larger angle. It should be understood that the combination of the proximal portion 841 and the distal portion 843 is configured to allow the intubation guide 842 to be oriented at or near the sclerotomy incision 316 or the suture loop assembly 330 described above. Therefore, as will be described in more detail below, the intubation guide 842 is operable to feed the cannula 820 into the appropriate position when the cannula 820 is advanced distally relative to the instrument. Although the cannulation guide 842 shown and described herein has a specific shape, it should be understood that in other examples the cannulation guide 842 may have any other suitable shape, which will be apparent to those skilled in the art in light of the teachings herein.

[0176] The cannula guide 842 typically has a cross-sectional shape corresponding to that of the cannula 820. For example, as described above, the cannula 820 has a substantially rectangular cross-section. Therefore, the cannula guide 842 may also have a corresponding rectangular cross-sectional shape. The cannula guide 842 is typically hollow, or includes a lumen (not shown) such that the cannula guide 842 is configured to receive the cannula 820 in a slidable manner. In addition to having a shape corresponding to that of the cannula 820, the cannula guide 842 also includes rounded edges such that the cannula guide 820 will not substantially cause external injury.

[0177] In this example, the cannulation guide 842 is constructed of a substantially rigid or semi-rigid material, such that the cannulation guide 842 retains its shape as the cannula 820 is advanced through it. Because the cannulation guide 842 is a non-invasive, rigid or semi-rigid guide, it should be understood that when the instrument is used in the method described above for choroidal delivery of therapeutic agents, the cannulation guide 842 may optionally be placed against the patient's eye or gently pressed to create leverage and help ensure tangential advancement of the cannula 820.

[0178] The cannula actuation assembly 900 in this example is substantially the same as the cannula actuation assembly 700 described above. For example, the cannula actuation assembly 900 includes a cannula slider 910, a pair of pinions (not shown), and a cannula advance wheel 940. The cannula actuation assembly 900 in this example operates in a similar manner to the cannula actuation assembly 700 with wheel 940, which can rotate to drive the pinions (not shown), which in turn drives the cannula slider 910, thereby advancing the cannula 820 relative to the body 840.

[0179] The needle actuation assembly 950 is similar to the needle actuation assembly 550 described above, except that the needle actuation assembly 950 of this example includes a different locking mechanism. As can be seen, the needle actuation assembly 950 includes a needle advance member 960 at least partially disposed within the cannula slide 910. The needle advance member 960 is substantially the same as the needle advance member 560 described above. For example, like the needle advance member 560, the needle advance member 960 of this example includes an actuation tab 962, which is substantially the same as the actuation tab 562 described above. As will be described in more detail below, in some examples, the actuation tab 962 can be used to rotate the needle advance member 960 to a vertical position, thereby unlocking the translation of the needle advance member 960 relative to the cannula slide 910.

[0180] Unlike the needle actuation assembly 550 described above, the needle actuation assembly 950 of this example lacks a component similar to the cam lock 570 described above. Instead, the needle actuation assembly 950 includes a locking collet 970 disposed around the body 840. The locking collet 970 is configured to engage the cannula slide 910 of the cannula actuation assembly 900 to selectively lock and unlock the translational movement of the cannula slide 910. As will be described in more detail below, the locking collet 970 is configured such that rotation of the locking collet 970 relative to the body 840 causes the locking collet 970 to switch between a locked state and an unlocked state.

[0181] Figures 32A-31C An exemplary operating mode using device 810 is shown. Specifically, device 810 is used in... Figure 32A The state shown begins. As can be seen, both the cannula actuation member 900 and the needle actuation assembly 950 can initially be in a retracted proximal position relative to the body 840. In this position, the cannula advance wheel 940 rotates to its farthest counterclockwise position. Correspondingly, the cannula slider 910 has been driven proximally to its nearest position within the body 840. Because the cannula 820 is securely fixed to the cannula slider 910, the cannula 820 is similarly positioned proximally relative to the body 840, such that the cannula 820 is positioned within the cannula guide 842. In this position, the needle 830 is also in a proximal position, such that the distal end of the needle 830 is positioned within the cannula 842.

[0182] To initiate the advancement of the cannula 820, if the locking head 970 is in the locked position, the operator can first rotate the locking head 970 of the needle actuation assembly 950. If the locking head 970 is in the unlocked position, the operator can optionally begin advancing the cannula 820 immediately without first moving the locking head 970 to the unlocked position. The operator can advance the cannula 820 by applying force to the cannula advance wheel 940 to rotate it counterclockwise relative to the body 840, such as... Figure 32BAs can be seen, because the teeth of the pinion (not shown) engage with the teeth of the cannula advance wheel 940 (not shown), the rotation of the cannula advance wheel 940 will cause the pinion to rotate clockwise accordingly. When the pinion rotates clockwise, the teeth of the pinion will engage with the teeth of the cannula slide 910 to translate the cannula slide 910 distally. Therefore, the counterclockwise rotation of the cannula advance wheel 940 will cause the cannula slide 910 to translate distally via the pinion. Because the cannula 820 is securely fixed to the cannula slide 910, the advancement of the cannula slide 910 will cause the cannula 820 to advance accordingly. When the cannula slide 910 is advanced, the needle advance assembly 950 can also move forward correspondingly due to the accidental friction between the multiple parts of the needle advance assembly 960 and the cannula slide 910.

[0183] Figure 32B An instrument 810 is shown with a cannula 820 in the fully advanced position. In the fully advanced position, the cannula slide 910 has been fully advanced relative to the body 840 by the operator fully rotating the cannula advance wheel 940 via a pinion. Although the cannula 820 has been fully advanced distally, it should be understood that at this stage, the needle 830 remains within the cannula 820 until the operator applies force distally to the needle advance member 960 to translate the needle advance member 960 relative to the cannula slide 910.

[0184] Once the cannula 820 has been fully advanced distally, the operator can initiate the process of advancing the needle 830. (As...) Figure 32C As can be seen, the needle advance member 960 is initially positioned such that there is at least some gap between the cannula slide 910 and the needle advance member 960. Although not shown, it should be understood that in some examples, such gaps can be maintained by a removable member disposed between the cannula slide 910 and the needle advance member 960. When the instrument 810 is equipped with such a removable member, such a removable member is removed before the advance of the needle 830 is initiated. Alternatively, the needle advance member 960 and the cannula slide 910 may include characteristic structures such as locking tabs and corresponding channels of locking tabs 569 similar to those of the needle advance member 560, and a lower receiving channel 529 of the cannula slide 510 described above with respect to the instrument 410. As described above, if the needle advance member 960 is equipped with such characteristic structures, the advance of the needle 830 (e.g., Figure 32CBefore proceeding (as shown), the needle advance member 960 is rotated to a vertical position. Once the operator has completed any unlocking steps, the operator can then lock the cannula slide 910 by rotating the locking clamp 970. Next, the needle 830 can be advanced as follows: the operator grasps the needle advance member 960 and translates it relative to the cannula slide 910 until the needle 830 is positioned in the desired position relative to the cannula 820. The therapeutic agent can then be delivered as described above, referring to the method for choroidal delivery of therapeutic agents.

[0185] VI. Exemplary Combinations

[0186] The following embodiments relate to various non-exhaustive ways in which the teachings herein can be combined or applied. It should be understood that the following embodiments are not intended to limit the scope of any claims that may be provided at any time in this patent application or a subsequent filing thereof. No disclaimer is intended. The following embodiments are provided for illustrative purposes only. It is contemplated that the various teachings herein may be arranged and applied in many other ways. It is also contemplated that certain variations may omit certain features mentioned in the following embodiments. Therefore, none of the aspects or features mentioned below should be considered definitive unless otherwise expressly indicated, for example, by the inventor or a successor of the inventor of interest, at a later date. If any claim provided in this patent application or a subsequent filing related to this patent application includes additional features beyond those mentioned below, such additional features should not be presumed to have been added for any reason related to patentability.

[0187] Example 1

[0188] A device for delivering a therapeutic agent to an eye, wherein the device includes: (a) a body; (b) a cannula movable relative to the body, wherein the cannula is sized and configured to be inserted between the choroid and sclera of a patient's eye, wherein the cannula defines a longitudinal axis; (c) a hollow needle slidable relative to the cannula; (d) a cannula actuation assembly operable to actuate the cannula relative to the body; and (e) a needle actuation assembly operable to actuate the needle relative to the cannula.

[0189] Example 2

[0190] According to the device of Embodiment 1, the cannulation actuation assembly and the needle actuation assembly are capable of operating independently of each other.

[0191] Example 3

[0192] According to the devices of Embodiments 1 and 2, the needle actuation assembly is responsive to actuation of the cannula relative to the body.

[0193] Example 4

[0194] According to the device of embodiment 3, the needle actuation component is configured to actuate the needle relative to the body when the cannula actuation component actuates the cannula relative to the body.

[0195] Example 5

[0196] The device according to any one or more of embodiments 1 to 4 further includes a locking feature structure, wherein the locking feature structure is operable to transition between a first state and a second state, wherein the locking feature structure is operable to lock the cannula actuation component, thereby preventing actuation of the cannula relative to the body when the locking feature structure is in the second state.

[0197] Example 6

[0198] According to the device of embodiment 5, the locking feature structure is operable to lock the needle actuation component, thereby preventing actuation of the needle relative to the cannula when the locking feature structure is in a first state.

[0199] Example 7

[0200] According to the device of embodiment 6, the locking feature structure includes a cam feature structure having an elliptical cross-section, and the cam feature structure is rotatable to cause the locking feature structure to transition between a first state and a second state.

[0201] Example 8

[0202] According to any one or more of embodiments 1 to 7, the cannulation actuation assembly includes a cannulation member, wherein the cannulation member is configured to translate relative to the body to actuate the cannulation relative to the body.

[0203] Example 9

[0204] According to the device of embodiment 8, the cannulation actuation assembly further includes a rack and gear assembly, wherein the rack and gear assembly is in communication with the cannulation member, and wherein the rack and gear assembly is configured to drive the translation of the cannulation member.

[0205] Example 10

[0206] According to any one or both of Embodiments 8 and 9, the cannulation member includes a lumen extending from a distal end of the cannulation member to a proximal end of the cannulation member, wherein the lumen is configured to slidably receive a needle.

[0207] Example 11

[0208] According to any one or more of embodiments 8 to 10, the needle actuation assembly includes a needle member, wherein at least a portion of the needle member is capable of being inserted into the cannula member.

[0209] Example 12

[0210] According to the device of embodiment 11, the needle member is configured to selectively translate relative to the cannulation member.

[0211] Example 13

[0212] According to the device of embodiment 12, the needle actuation assembly further includes an actuation selector, wherein the actuation selector responds to rotation of the needle member to simultaneously unlock translation of the needle member relative to the cannula member and lock translation of the cannula member relative to the body.

[0213] Example 14

[0214] The device according to any one or more of embodiments 1 to 13 further includes an intubation guide, wherein the intubation guide extends distally from the body, and wherein the intubation guide is configured to guide the intubation along a predetermined path.

[0215] Example 15

[0216] According to the device of embodiment 14, the cannulation guide includes a lumen extending from a proximal end of the cannulation guide to a distal end, wherein the lumen is configured to receive the cannula and guide the cannula along a predetermined path.

[0217] Example 16

[0218] A device for delivering a therapeutic solution to an eye, wherein the device includes: (a) a body; (b) a cannula, wherein the cannula is sized and configured to be inserted between the choroid and sclera of a patient's eye, wherein the cannula includes a needle lumen extending therethrough; (c) a hollow needle, wherein the needle is configured to slidably engage the needle lumen of the cannula; and (d) an actuation assembly, wherein the actuation assembly includes: (i) a cannula actuator and (ii) a needle actuator.

[0219] Example 17

[0220] The device according to embodiment 16 further includes an actuation mechanism configured to drive the cannula actuator distally relative to the body.

[0221] Example 18

[0222] According to the device of embodiment 17, the actuation mechanism includes a wheel and a gear, wherein the wheel has a plurality of teeth, wherein the teeth are configured to engage with a plurality of corresponding teeth of the gear, wherein the cannula actuator is in communication with the gear.

[0223] Example 19

[0224] A method of applying a therapeutic solution to a patient's eye, the method comprising the steps of: (a) passing a suture through the patient's eye to form at least one loop defined by the suture; (b) making an incision in at least a portion of the eye to provide access to the choroid of the eye; (c) positioning a cannula guide of an instrument near the eye such that a distal end of the cannula guide is positioned adjacent to the at least one loop defined by the suture; (d) advancing a cannula through the at least one loop defined by the suture and into an incision formed by an actuator of the advancing instrument that has made an incision in at least a portion of the eye; and (e) advancing a needle through the cannula to penetrate the choroid and applying the therapeutic solution by a second actuator that advances the instrument.

[0225] Example 20

[0226] According to the method of embodiment 19, the method further includes locking the cannula relative to the instrument before the locking feature structure of the instrument advances the needle through the cannula.

[0227] VII. Other aspects

[0228] Although the processes and apparatus described herein are discussed in the context of the treatment of age-related macular degeneration, it should be understood that such limitations are not intended or implied. The processes and apparatus described herein can be used to treat a variety of other types of medical conditions. By way of example only, the processes and apparatus (and variations thereof) described herein can be used to treat retinitis pigmentosa, diabetic retinopathy, wet age-related macular degeneration, and / or other medical conditions. Various suitable medical contexts in which the processes and apparatus described herein can be used will be apparent to those skilled in the art.

[0229] It should be understood that any type of device described herein may also include various other features in addition to or as alternatives to those described above. By way of example only, any device herein may also include one or more of the various features disclosed in any of the various references incorporated herein by reference.

[0230] It should be understood that any one or more of the teachings, expressions, embodiments, examples, etc., described herein may be combined with any one or more of the other teachings, expressions, embodiments, examples, etc., described herein. Therefore, the aforementioned teachings, expressions, embodiments, examples, etc., should not be considered independent of each other. Various suitable ways in which the teachings herein can be combined will be apparent to those skilled in the art upon reference to the teachings herein. Such modifications and variations are intended to be included within the scope of the claims.

[0231] It should be understood that any patent, publication, or other public material allegedly incorporated herein by reference, whether in whole or in part, is incorporated only to the extent that the incorporated material does not conflict with the definitions, statements, or other public materials set forth in this disclosure. Therefore, and to the extent necessary, the disclosure expressly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or part thereof, allegedly incorporated herein by reference that conflicts with existing definitions, statements, or other public materials set forth herein is incorporated only to the extent that it does not conflict with existing public materials.

[0232] The aforementioned types may be designed to be discarded after a single use, or they may be designed to be used multiple times. In either or both cases, the repairable type is designed for reuse after at least one use. Refitting may include any combination of the following steps: disassembling the device, then cleaning or replacing specific parts, and subsequently reassembling. Specifically, some types of the device may be disassembled, and any number of specific parts or portions of the device may be replaced or removed selectively in any combination. Some types of the device may be reassembled at a repair facility or by an operator just before surgery for subsequent use while cleaning and / or replacing specific parts. Those skilled in the art will appreciate that device repair can utilize a variety of techniques for disassembly, cleaning / replacement, and reassembly. The use of these techniques and the resulting repaired devices are all within the scope of this application.

[0233] By way of example only, the forms described herein can be sterilized before and / or after the procedure. In one sterilization technique, the device is placed in a closed and sealed container, such as a plastic bag or a TYVEK bag. The container and device can then be placed in a radiation field that can penetrate the container, such as gamma radiation, X-rays, or high-energy electrons. The radiation kills bacteria on the device and in the container. The sterilized device can then be stored in a sterile container for later use. Any other techniques known in the art can also be used to sterilize the device, including but not limited to beta or gamma radiation, ethylene oxide, or vapor.

[0234] Various embodiments of the invention have been shown and described, and further improvements to the methods and systems described herein can be achieved by suitable modifications made by those skilled in the art without departing from the scope of the invention. Several such potential modifications have been mentioned, and other modifications will be apparent to those skilled in the art. For example, the examples, embodiments, geometries, materials, dimensions, ratios, steps, etc., discussed above are illustrative and not essential. Therefore, the scope of the invention should be considered in accordance with the following claims and should be understood as not being limited to the details of the structures and operations shown and described in the specification and drawings.

Claims

1. A device for delivering a therapeutic agent to an eye, wherein the device for delivering the therapeutic agent to the eye comprises: (a) The main body; (b) A flexible cannula, the flexible cannula being movable relative to the main body, wherein the flexible cannula is sized and constructed to be inserted between the choroid and sclera of the patient's eye and conforms to the curvature of the patient's eye as the flexible cannula slides along the choroidal space between the choroid and sclera of the patient's eye, wherein the flexible cannula defines a longitudinal axis, wherein the flexible cannula has an opening, wherein the flexible cannula includes a trauma-resistant distal end, wherein the flexible cannula has a rectangular cross-sectional shape; (c) A hollow needle, wherein the hollow needle has a sharp distal end and is capable of sliding relative to the flexible cannula within the flexible cannula; (d) A cannula actuation assembly, wherein the cannula actuation assembly is operable to actuate the flexible cannula relative to the body; as well as (e) A needle actuation assembly, wherein the needle actuation assembly is operable to advance the hollow needle through the opening of the flexible cannula, thereby passing through the choroid and delivering a therapeutic agent; The needle actuation assembly includes a needle member, and the cannula actuation assembly includes a cannula member, wherein the needle member is configured to selectively translate relative to the cannula member, and wherein the needle actuation assembly further includes an actuation selector, wherein the actuation selector responds to rotation of the needle member to simultaneously unlock translation of the needle member relative to the cannula member and lock translation of the cannula member relative to the body.

2. The device for delivering a therapeutic agent to the eye according to claim 1, wherein the cannulation actuation assembly and the needle actuation assembly are operable independently of each other.

3. The device for delivering a therapeutic agent to the eye according to claim 1, wherein the needle actuation component is responsive to actuation of the flexible cannula relative to the body.

4. The device for delivering a therapeutic agent to the eye according to claim 3, wherein the needle actuation component is configured to actuate the hollow needle relative to the body when the cannula actuation component actuates the flexible cannula relative to the body.

5. The device for delivering a therapeutic agent to the eye according to claim 1, further comprising a locking feature structure, wherein the locking feature structure is operable to transition between a first state and a second state, wherein the locking feature structure is operable to lock the cannula actuation assembly, thereby preventing actuation of the flexible cannula relative to the body when the locking feature structure is in the second state.

6. The device for delivering a therapeutic agent to the eye according to claim 5, wherein the locking feature is operable to lock the needle actuation assembly, thereby preventing actuation of the hollow needle relative to the flexible cannula when the locking feature is in the first state.

7. The device for delivering a therapeutic agent to the eye according to claim 6, wherein the locking feature structure includes a cam feature structure having an elliptical cross-section, wherein the cam feature structure is rotatable to cause the locking feature structure to transition between the first state and the second state.

8. The device for delivering a therapeutic agent to the eye according to claim 1, wherein the cannulation member is configured to translate relative to the body to actuate the flexible cannula relative to the body.

9. The device for delivering a therapeutic agent to the eye according to claim 8, wherein the cannulation actuation assembly further comprises a rack and gear assembly, wherein the rack and gear assembly is in communication with the cannulation member, wherein the rack and gear assembly is configured to drive translation of the cannulation member.

10. The device for delivering a therapeutic agent to the eye according to claim 8, wherein the cannulation member includes a lumen extending from a distal end of the cannulation member to a proximal end of the cannulation member, wherein the lumen is configured to slidably receive the hollow needle.

11. The device for delivering a therapeutic agent to the eye according to claim 8, wherein at least a portion of the hollow needle is insertable into the cannulation member.

12. The device for delivering a therapeutic agent to the eye according to claim 1, further comprising a cannulation guide, wherein the cannulation guide extends distally from the body, wherein the cannulation guide is configured to guide the flexible cannula along a predetermined path.

13. The device for delivering a therapeutic agent to the eye according to claim 12, wherein the cannulation guide includes a lumen extending from a proximal end to a distal end of the cannulation guide, wherein the lumen is configured to receive the flexible cannula and guide the flexible cannula along the predetermined path.

14. A device for delivering a therapeutic agent to an eye, wherein the device for delivering the therapeutic agent to the eye comprises: (a) The main body; (b) A flexible cannula, wherein the flexible cannula is sized and configured to be inserted between the choroid and sclera of a patient's eye and conforms to the curvature of the patient's eye as the flexible cannula slides along the choroidal space between the choroid and sclera of the patient's eye, wherein the flexible cannula includes a needle lumen extending therethrough, wherein the flexible cannula includes a trauma-resistant distal end, wherein the flexible cannula has a rectangular cross-sectional shape; (c) An intubation guide, wherein the intubation guide extends distally from the body, wherein the intubation guide includes: (i) an inner lumen configured to receive the flexible cannula; and (ii) A curved distal portion, the distal portion being curved from the longitudinal axis of the body, wherein the cannula guide is operable to feed the flexible cannula into place as it is advanced distally relative to the body. (d) A hollow needle having a sharp distal end, wherein the hollow needle is configured to slidably engage the lumen of the flexible cannula; and (e) An actuation assembly, wherein the actuation assembly includes: (i) Intubation actuator, and (ii) Needle actuator; The needle actuator includes a needle member, and the cannula actuator includes a cannula member, wherein the needle member is configured to selectively translate relative to the cannula member, and wherein the needle actuator further includes an actuation selector, wherein the actuation selector responds to rotation of the needle member to simultaneously unlock translation of the needle member relative to the cannula member and lock translation of the cannula member relative to the body.

15. The device for delivering a therapeutic agent to the eye according to claim 14, further comprising an actuation mechanism, wherein the actuation mechanism is configured to drive the cannulation actuator distally relative to the body.

16. The device for delivering a therapeutic agent to the eye according to claim 15, wherein the actuation mechanism includes a pinion and a rack portion, wherein the pinion has a plurality of teeth, wherein the teeth are configured to engage the teeth of the rack portion, wherein the cannulation member communicates with the rack portion.

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