Method and apparatus for sensing position between layers of an eye

Abstract

The present invention discloses a device (10) for delivering a therapeutic agent to an eye, the device comprising a body (40), a cannula (20), a hollow needle (30), an actuation assembly (60) and a detection / visualization system. The cannula extends distally from the body and is sized and configured to be inserted between the choroid and sclera of a patient's eye. The actuation assembly is operable to actuate the needle relative to the cannula, thereby driving the distal portion of the needle along an exit axis. The cannula can be inserted through a scleral incision and advanced through the choroid to deliver the therapeutic agent to the vicinity of a potential space between a neurosensory retina and a retinal pigment epithelial cell layer. The detection / visualization system is operable to detect or visualize penetration of the choroid of a patient's eye and provide feedback to an operator and / or automatic control of the device based on the penetration of the choroid.

Description

[0001] This application is a divisional application of international application PCT / US2015 / 049425, which entered the Chinese national phase on May 10, 2017 and is entitled “Method and apparatus for sensing position between layers of the eye” and has Chinese application number 2015800611845 and international application date September 10, 2015.

[0002] priority

[0003] This application claims priority to U.S. Provisional Patent Application No. 62 / 049,079, filed on September 11, 2014, entitled “Suprachoroidal Sensing Technology,” the disclosure of which is incorporated herein by reference.

[0004] Joint Research Statement

[0005] The subject matter disclosed in this patent application was developed by or on behalf of one or more parties to a joint research contract, and the claimed invention was made by or on behalf of one or more parties to a joint research contract, which was in effect on or before the effective filing date of the claimed invention. The claimed invention resulted 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 Art

[0006] The human eye comprises several layers. The white outer layer is the sclera, which surrounds the choroid layer. The retina is located inside the choroid layer. The sclera contains collagen fibers and elastic fibers that provide protection for the choroid and retina. The choroid layer includes a vascular system that provides oxygen and nutrition to the retina. The retina includes light-sensitive tissue, which includes rods and cones. The macula is located at the center of the retina at the back of the eye, usually centered on the axis (i.e., the visual axis) that passes through the center of the lens and cornea of ​​the eye. The macula provides central vision, specifically provided by cones.

[0007] Macular degeneration is a medical condition that affects the macula, so that people with macular degeneration can retain a certain degree of peripheral vision while experiencing a loss of or a decline in central vision. Macular degeneration can be caused by a variety of factors, such as age (also known as "AMD") and genetics. Macular degeneration can occur in a "dry" (non-exudative) form, in which cell debris called drusen accumulates between the retina and the choroid, resulting in a map atrophy area. Macular degeneration can also occur in a "wet" (exudative) form, in which blood vessels grow out of the choroid behind the retina. Although people with macular degeneration can retain a certain degree of peripheral vision, the loss of central vision can have a significant negative impact on the quality of life. In addition, the quality of the peripheral vision retained may decline and may also disappear in some cases. Therefore, it is desirable to provide a treatment for macular degeneration in order to prevent or eliminate the vision loss caused by macular degeneration. In some cases, it is desirable to provide such treatment in a highly concentrated manner, such as by delivering a therapeutic substance to the subretinal layer (above the sensory nerve layer of the retina and below the retinal pigment epithelium) of the map atrophy area immediately adjacent to the macula. However, because the macula is located at the back of the eye and beneath the sensitive layer of the retina, it can be difficult to physically reach the macula.

[0008] While a variety of surgical methods and instruments for treating the eye have been developed and used, it is believed that no one prior to the inventors has developed or used the invention described in the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] While the specification concludes with claims that particularly point out and distinctly claim the technology, it is believed that the technology will be better understood from the following description of certain examples read in conjunction with the accompanying drawings in which like reference numerals identify similar elements, and wherein:

[0010] Figure 1 shows a perspective view of an exemplary apparatus for subretinal administration of a therapeutic agent from a suprachoroidal route;

[0011] Figure 2 Shows Figure 1 A side elevation view of the device;

[0012] Figure 3 Shows Figure 1 another side elevation view of the instrument with the locking member removed;

[0013] Figure 4 Shows Figure 1 another side elevation view of the device of claim 1, wherein the actuation member is advanced distally to extend the needle distally from the cannula;

[0014] Figure 5 Shows that it can be combined with Figure 1A perspective view of a distal end of an exemplary cannula in an apparatus of

[0015] Figure 6 Shows Figure 5 A cross-sectional view of a cannula, wherein the cross section is along Figure 5 The line 6-6 intercepts;

[0016] Figure 7 shows a perspective view of another exemplary alternative apparatus for subretinal administration of a therapeutic agent from a suprachoroidal route;

[0017] Figure 8 A perspective view of an exemplary suture measurement template for an exemplary method of subretinal administration of a therapeutic agent from a suprachoroidal approach is shown;

[0018] Fig. 9A A top plan view of a patient's eye is shown with the surrounding structures of the eye secured and the chandelier mounted;

[0019] Fig. 9B Shows Fig. 9A The top plan view of the eye, where Figure 8 The template is set on the eye;

[0020] Fig. 9C Shows Fig. 9A A top plan view of an eye, wherein a plurality of markers are disposed on the eye;

[0021] Fig.9D Shows Fig. 9A A top plan view of an eye with a suture loop attached to the eye;

[0022] Fig.9E Shows Fig. 9A Top plan view of the eye where a sclerotomy is being performed;

[0023] Fig.9F Shows Fig. 9A The top plan view of the eye, where Figure 1 The instrument is being inserted through the sclerotomy opening between the sclera and choroid of the eye;

[0024] Figure 9G Shows Fig. 9A The top plan view of the eye, where Figure 1 The device is placed between the sclera and choroid under direct visualization at the back of the eye;

[0025] Figure 9H Shows Fig. 9A The top plan view of the eye, where Figure 1The needle of the device is advanced under direct visualization at the back of the eye, thereby pressing against the outer surface of the choroid so that the choroid 'tents';

[0026] Fig.9I Shows Fig. 9A a top plan view of an eye with a needle dispensing a lead bleb under direct visualization at the back of the eye, the needle being located between the sclera and the choroid, and the lead bleb being located in the subretinal space between the choroid and the retina;

[0027] Figure 9J Shows Fig. 9A A top plan view of an eye with a needle dispensing a therapeutic agent into the eye at the back of the eye between the sclera and the choroid;

[0028] Fig. 10A Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Fig. 9A The line 10A-10A is intercepted;

[0029] Fig. 10B Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Fig.9E The line 10B-10B is intercepted;

[0030] Fig. 10C Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Fig.9F The line 10C-10C is intercepted;

[0031] Fig. 10D Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Figure 9G The line 10D-10D is intercepted;

[0032] Fig. 10E Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Figure 9H The line 10E-10E is intercepted;

[0033] Fig.10F Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Fig.9I The line 10F-10F is intercepted;

[0034] Figure 10G Shows Fig. 9A A cross-sectional view of an eye, wherein the cross section is around Figure 9J The line 10G-10G is intercepted;

[0035] Fig.11A Shows Fig. 9A Detailed cross-sectional view of an eye shown in Fig. 10E The status shown;

[0036] Fig. 11B Shows Fig. 9A Detailed cross-sectional view of an eye shown in Fig.10F The status shown;

[0037] Fig. 11C Shows Fig. 9A Detailed cross-sectional view of an eye shown in Figure 10G The status shown;

[0038] Fig.12 A schematic diagram of an exemplary system for subretinal administration of a therapeutic agent from a suprachoroidal route is shown;

[0039] Fig.13 Shows Fig.12 A schematic diagram of an exemplary interferometer subsystem of a system of;

[0040] Fig.14 Shows Fig.13 A detailed schematic diagram of an exemplary power supply for an interferometer system;

[0041] Fig.15 Shows Fig.13 A detailed schematic diagram of an exemplary light source of an interferometer system;

[0042] Fig.16 Shows Fig.13 A detailed schematic diagram of an exemplary position tracking system of an interferometer system;

[0043] Fig.17 Shows Fig.13 A detailed schematic diagram of an exemplary interferometer of an interferometer system of FIG.

[0044] Fig.18 Shows Fig.13 A detailed schematic diagram of an exemplary spectrometer of an interferometer system;

[0045] Fig.19 Shows Fig.13 A detailed schematic diagram of an exemplary optical probe of an interferometer system;

[0046] Fig. 20 Shows Figure 1 The distal end of the needle of the device and Fig.19 A perspective view of the optical probe;

[0047] Fig.21 Shows Fig. 20 A top view of the distal end of the needle in combination with the probe;

[0048] Fig. 22 Shows Fig.19 A side cross-sectional view of an optical probe;

[0049] Fig.23A Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 5 The cannula is placed between the sclera and the choroid under direct visualization at the back of the eye, and wherein Fig.19 The optical probe transmits and receives light through the choroid and retina;

[0050] Fig. 23B Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 5 The cannula is advanced between the sclera and choroid under direct visualization at the back of the eye, and wherein Fig.19 The optical probe transmits and receives light through the choroid and retina;

[0051] Fig.24A Shown by Fig.19 The optical probe is Fig.23A A graph of an optical coherence tomography (OCT) scan performed at the indicated location;

[0052] Fig. 24B Shown by Fig.19 The optical probe is Fig. 23B A graph of an optical coherence tomography scan performed at the indicated location;

[0053] Fig.25 A schematic diagram of another exemplary system for subretinal administration of a therapeutic agent from a suprachoroidal route is shown;

[0054] Fig.26A Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 5 The cannula is placed between the sclera and the choroid under direct visualization at the back of the eye, and wherein Fig.25 The light source of the system emits light into the choroid of the eye;

[0055] Fig.26B Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 5 The cannula is advanced between the sclera and choroid under direct visualization at the back of the eye, and wherein Fig.26A The light source emits light into the choroid of the eye;

[0056] Fig.26C Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 1The needle of the device is further advanced between the sclera and the choroid under direct visualization at the back of the eye, and wherein Fig.26A The light source transmits light through the retina and vitreous body of the eye;

[0057] Fig.27A Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 5 The cannula is placed between the sclera and the choroid under direct visualization at the back of the eye, and wherein Fig.26A A light source emits light into the choroid of the eye; and

[0058] Fig.27B Shows Fig. 9A Detailed cross-sectional view of the eye, where Figure 1 The needle of the device is advanced between the sclera and the choroid under direct visualization at the back of the eye, and wherein Fig.26A The light source transmits light through the retinal pigment epithelium and vitreous body of the eye.

[0059] The drawings are not intended to be limiting in any way, and it is contemplated that various embodiments of the technology may be performed in a variety of other ways, including those not necessarily shown in the drawings. The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several aspects of the technology and, together with the description, serve to explain the principles of the technology; however, it should be understood that the technology is not limited to the precise arrangements shown. DETAILED DESCRIPTION

[0060] The following description of certain examples of the present technology should not be used to limit its scope. Other examples, features, aspects, embodiments and advantages of the present technology will be apparent to those skilled in the art from the following description, which is by way of example, one of the best ways contemplated for implementing the present technology. As will be appreciated, the technology described herein can include other different and obvious aspects, all without departing from the present technology. Therefore, the drawings and specific embodiments should be regarded as illustrative in nature and not restrictive.

[0061] 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. The following teachings, expressions, embodiments, examples, etc. should therefore not be considered isolated from each other. With reference to the teachings herein, various suitable ways in which the teachings herein may be combined will be apparent to those of ordinary skill in the art. Such modifications and variations are intended to be included within the scope of the claims.

[0062] For clarity of disclosure, the terms "proximal" and "distal" are defined herein relative to a surgeon or other operator holding a surgical instrument having a distal surgical end effector. The term "proximal" refers to a position of an element closer to the surgeon or other operator, and the term "distal" refers to a position of an element closer to the surgical end effector of the surgical instrument and further away from the surgeon or other operator.

[0063] I. Exemplary Instruments with Slider Articulation Features

[0064] Figure 1-Figure 4 An exemplary apparatus (10) is shown that is configured to be used in a process of subretinal administration of a therapeutic agent to a patient's eye from a suprachoroidal approach. The apparatus (10) includes a flexible cannula (20), a body (40), and a slider (60). The cannula (20) extends distally from the body (40) and has a generally rectangular cross-section. The cannula (20) is generally configured to support a needle (30) that can slide within the cannula (20), as will be described in more detail below.

[0065] In the present example, cannula (20) comprises a flexible material, such as polyether block amide (PEBA), which may be manufactured under the trade name PEBAX. Of course, any other suitable material or combination of materials may be used. Also in the present example, cannula (20) has a cross-sectional profile dimension of approximately 2.0 mm x 0.8 mm and a length of approximately 80 mm. Alternatively, any other suitable dimensions may be used.

[0066] As will be described in more detail below, the cannula (20) is sufficiently flexible to conform to the specific structure and contours of the patient's eye, yet the cannula (20) has sufficient column strength to allow the cannula (20) to be advanced between the sclera and choroid of the patient's eye without buckling. Several factors may contribute to the suitable flexibility of the cannula (20). For example, the durometer of the material used to configure the cannula (20) at least partially characterizes the flexibility of the cannula (20). 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 fall within the range of about 27D to about 46D; or more specifically, within the range of about 33D to about 46D; or more specifically, within the range of about 40D to about 45D. The specific cross-sectional shape of the cannula (20) may also at least partially characterize the flexibility of the cannula (20). Additionally, the stiffness of needle (30) disposed within cannula (20) may at least partially characterize the flexibility of cannula (20).

[0067] In the present example, the flexibility of cannula (20) may be quantified by calculating the bending stiffness of cannula (20). Bending stiffness is calculated by multiplying the elastic modulus and the area moment of inertia. By way of example only, an exemplary material that may be used to form cannula (20) may have a Shore hardness of D27, a hardness of 1.2×10 7 N / m 2 The elastic modulus (E) and 5.52×10 -14 m 4 Area moment of inertia (I x ), thus providing 0.7×10 -6 Nm 2 Another exemplary material that can be used to form the cannula (20) can have a Shore hardness of D33, a hardness of 2.1×10 7 N / m 2 The elastic modulus (E) and 5.52×10 -14 m 4 Area moment of inertia (I x ), thus providing 1.2×10 -6 Nm 2 Another exemplary material that can be used to form the cannula (20) can have a Shore hardness of D42, a hardness of 7.7×10 7 N / m 2 The elastic modulus (E) and 5.52×10 -14 m 4 Area moment of inertia (I x ), thus providing 4.3×10 -6 Nm 2 Another exemplary material that can be used to form the cannula (20) can have a Shore hardness of D46, a hardness of 17.0×10 7 N / m 2 The elastic modulus (E) and 5.52×10 -14 m 4 Area moment of inertia (I x ), thus providing 9.4×10 -6 Nm 2 The calculated bending stiffness about the x-axis is . Thus, by way of example only, the bending stiffness of the cannula (20) may fall within the range of about 0.7×10 -6 Nm 2 to about 9.4×10 -6 Nm 2 or more specifically about 1.2×10 -6 Nm 2 to about 9.4×10 -6 Nm 2or more specifically about 2.0×10 -6 Nm 2 About 7.5×10 -6 Nm 2 or more specifically about 2.0×10 -6 Nm 2 About 6.0×10 -6 Nm 2 or more specifically about 3.0×10 -6 Nm 2 to about 5.0×10 -6 Nm 2 or more specifically about 4.0×10 -6 Nm 2 to about 5.0×10 -6 Nm 2 within the range.

[0068] In this example, the flexibility of the cannula (20) can also be quantified by the following formula:

[0069] (1)

[0070] In the above equation, the bending stiffness (EI) is calculated experimentally by deflecting a cannula (20) having a fixed span (L) a set 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 may be deflected 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 a 5.5×10 -6 Nm 2 In another exemplary material that can be used to form the cannula (20), a force of 0.0205 N may be required to achieve a deflection of 0.0135 m, thereby providing a 6.8×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0199 N may be required to achieve a deflection of 0.0099 m, thereby providing a 9.1×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0241 N may be required to achieve a deflection of 0.0061 m, thereby providing a 1.8×10 -6 Nm 2In yet another exemplary material that may be used to form cannula (20), a force of 0.0190 N may be required to achieve a deflection of 0.0081 m, thereby providing a 1.0×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0215 N may be required to achieve a deflection of 0.0114 m, thereby providing a bending stiffness of 8.4×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0193 N may be required to achieve a deflection of 0.0170 m, thereby providing a 5.1×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0224 N may be required to achieve a deflection of 0.0152 m, thereby providing a 6.6×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0183 N may be required to achieve a deflection of 0.0119 m, thereby providing a 6.9×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0233 N may be required to achieve a deflection of 0.0147 m, thereby providing a 7.1×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0192 N may be required to achieve a deflection of 0.0122, thereby providing a 7.1×10 -6 Nm 2 In yet another exemplary material that may be used to form cannula (20), a force of 0.0201 N may be required to achieve a deflection of 0.0201, thereby providing a 4.5×10 -6 Nm 2 The calculated bending stiffness about the x-axis is . Thus, by way of example only, the bending stiffness of the cannula (20) may fall within the range of about 1.0×10 -6 Nm 2 About 9.1×10 -6 Nm 2 It should be understood that in other examples, the bending stiffness of the cannula may fall within the range of about 0.7×10 -6 Nm 2to about 11.1×10 -6 Nm 2 or more specifically about 2.0×10 -6 Nm 2 About 6.0×10 -6 Nm 2 within the range.

[0071] The needle (30) may have a bending stiffness that is different from the bending stiffness of the cannula (20). By way of example only, the needle (30) may be made of a cannula having a bending stiffness of 7.9×10 10 N / m 2 The elastic modulus (E) and 2.12×10 -17 m 4 Area moment of inertia (I x ) of Nitinol material, thereby providing 1.7×10 -6 Nm 2 By way of further example only, the bending stiffness of the needle (30) may fall within the range of about 0.5×10 -6 Nm 2 About 2.5×10 -6 Nm 2 or more specifically about 0.75×10 - 6 Nm 2 About 2.0×10 -6 Nm 2 or more specifically about 1.25×10 -6 Nm 2 About 1.75×10 -6 Nm 2 within the range.

[0072] As in Figure 5 and Figure 6 As can be seen in the figure, the cannula (20) includes two side lumens (22) and a single central lumen (24) extending longitudinally through the cannula (20) and terminating at an atraumatic beveled distal end (26). The beveled lateral opening (28) is located proximal to the beveled distal end (26). The side lumens (22) contribute to the flexibility of the cannula (20). Although the lumens (22) and lumens (24) are shown as opening at the beveled distal end (26), it should be understood that in some examples, the side lumens (22) and lumens (24) may optionally be closed at the beveled distal end (26). As will be described in more detail below, the central lumen (24) is configured to receive a needle (30) and a needle guide (80). In some versions, an optical fiber (not shown) is also disposed in the central lumen (24) near the needle (30). Such optical fibers can be used to provide illumination and / or optical feedback, as will be described in more detail below.

[0073] The beveled distal end (26) is generally angled to provide separation between the sclera and choroid layers, thereby enabling the cannula (20) to be advanced between these layers without trauma to the sclera or choroid layers. In this example, the beveled distal end (26) is angled about 15° relative to the longitudinal axis of the cannula (20) in this example. ° In other examples, the bevel angle of the beveled distal end (26) may be about 5 ° to about 50 ° or more specifically about 5 ° to about 40 ° or more specifically about 10 ° to about 30 ° or more specifically about 10 ° to about 20 ° within the range.

[0074] The needle guide (80) is disposed within the lumen (24) such that the distal end of the needle guide (80) abuts the beveled lateral opening (28). The needle guide (80) is typically configured to guide the needle (30) upwardly through the beveled opening (28) of the cannula (20) along an exit axis (EA) that is obliquely oriented 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 or materials. The shape of the needle guide (80) is configured to be inserted into the central lumen (24). In this example, the needle guide (80) is secured within the central lumen (24) by a pressure or interference fit, but in other examples, an adhesive and / or a mechanical locking mechanism may be used to secure the needle guide (80).

[0075] As in Figure 6 As best seen in the drawings, 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 upwardly away from the longitudinal axis of the cannula (20). The curved distal portion (88) of the present example is curved to guide the needle (30) along an exit axis (EA) that is approximately 7 degrees relative to the longitudinal axis (LA) of the cannula (20). ° to about 9 °The curved distal portion (88) extends distally from the cannula (20) at an angle of about 5°. It will be appreciated that this angle may be advantageous for flexing the needle (30) in a direction to ensure that the needle penetrates into the choroid (306) and minimizes the likelihood that the needle (30) will always pass through the suprachoroidal space below the choroid (306) (as opposed to penetrating the choroid (306)) and the likelihood of retinal perforation. By way of another example only, the curved distal portion (88) may force the needle (30) to exit the cannula (20) along an exit axis (EA) that is about 5° relative to the longitudinal axis (LA) of the cannula (20). ° to about 30 ° Or more specifically, at an angle of about 5 relative to the longitudinal axis (LA) of the cannula (20); ° to about 20 ° Or more specifically, at an angle of about 5 relative to the longitudinal axis (LA) of the cannula (20); ° to about 10 ° angular orientation within the range of .

[0076] The needle (30) is in the form of an internal cannula having a sharp distal end (32) and defining an internal lumen (34). The distal end (32) of this example has a lancet configuration. In some other versions, the distal end (32) has a three-bevel configuration or any other configuration, as described in U.S. patent application 14 / 619,256, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agent" filed on February 11, 2015, the disclosure of which is incorporated herein by reference. With reference to the teachings of this article, other suitable forms that the distal end (32) can take will be apparent to those of ordinary skill in the art. The needle (30) of this example includes a stainless steel hypodermic needle, which is designed to deliver a therapeutic agent while being small enough to minimize the collateral trauma when the needle (30) penetrates the patient's ocular tissue structure, as will be described in more detail below. Although stainless steel is used in this example, it should be understood that any other suitable material may also be used, including but not limited to nitinol and the like.

[0077] By way of example only, needle (30) may be 35 gauge with an inner diameter of 100 μm, although other suitable sizes may be used. For example, the outer diameter of needle (30) may fall within the range of 27 gauge to 45 gauge; or more specifically, within the range of 30 gauge to 42 gauge; or more specifically, within the range of 32 gauge to 39 gauge. As another merely illustrative example, the inner diameter of needle (30) may fall within the range of about 50 μm to about 200 μm; or more specifically, within the range of about 50 μm to about 150 μm; or more specifically, within the range of about 75 μm to about 125 μm.

[0078] Re-reference Figure 1-Figure 2 , the body (40) is generally shaped as an elongated rectangle with a curved distal end. The particular 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 a robotic arm to facilitate positioning of the instrument (10), as described in U.S. Patent Application No. 14 / 619,256, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agents," filed on February 11, 2015, the disclosure of which is incorporated herein by reference.

[0079] The actuation assembly (60) includes an actuation member (62) and a locking member (66). The locking member (66) is removably attachable to the body engagement portion (50) between the body (40) and the actuation member (62). As will be described in more detail below, the locking member (66) fills the space between the body (40) and the actuation member (62) to prevent the actuation member (62) from being advanced distally relative to the body (40). However, the locking member (66) is removable to selectively allow the actuation member (62) to be advanced distally relative to the body (40).

[0080] Figure 2-Figure 4 An exemplary actuation of the device (10) is shown. Specifically, as shown in Figure 2 As can be seen in the figure, needle (30) is initially retracted into cannula (20) and locking member (66) is positioned between body (40) and actuation member (62), thereby preventing advancement of actuation member (62). With instrument (10) in this configuration, cannula (20) may be positioned within an eye of a patient, as will be described in greater detail below.

[0081] Once cannula (20) is positioned within the patient's eye, the operator may wish to advance needle (30) relative to cannula (20). To advance needle (30), the operator may first remove locking member (66) by pulling locking member (66) away from instrument (10), as in Figure 3. 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, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agents," filed on February 11, 2015, the disclosure of which is incorporated herein by reference. The actuating member (62) of this example is only configured to translate the needle (30) and cannot rotate the needle (30). In other examples, it may be desirable to rotate the needle (30). Therefore, an alternative example may cause the actuating member (62) to include a feature structure for rotating and translating the needle (30).

[0082] In this example, if Figure 4 As shown, advancing the actuation member (62) into contact with the body (40) corresponds to advancing the needle (30) to a position relative to the cannula (20) to achieve a predetermined penetration amount in the patient's eye. In other words, the device (10) is configured so that the operator only needs to advance the actuation member (62) into contact with the body (40) to properly position the needle (30) in the patient's eye. In some examples, the predetermined advancement amount 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 actuation member (62) and the body (40) may not have a particular meaning other than the maximum advancement of the needle (30) relative to the cannula (20). Instead, the instrument (10) may be equipped with certain tactile feedback features to indicate to the operator when the needle (30) has been advanced to a certain predetermined distance relative to the cannula (20). Thus, the operator may determine the desired depth of penetration of the needle (30) into the patient's eye based on direct visualization of the markings on the instrument and / or based on tactile feedback from the instrument (10). Of course, such tactile feedback features may be combined with the present example, as will be apparent to one of ordinary skill in the art in view of the teachings herein.

[0083] II. Exemplary Alternative Devices and Features

[0084] In some examples, it may be desirable to change certain components or features of the apparatus described herein. For example, it may be desirable to use an apparatus similar to apparatus (10) having an alternative mechanism for actuating needle (30). However, in other examples, it may be desirable to use an apparatus similar to apparatus (10) equipped with a different cannula (20) or needle (30) geometry. An apparatus 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 having different physical properties. Although variations of certain examples are described herein, it should be understood that the apparatus described herein may include any other alternative features, which will be apparent to those of ordinary skill in the art in light of the teachings herein.

[0085] Figure 7 An exemplary alternative apparatus (2010) similar to the apparatus (10) described above is shown. Although certain features and operability of the apparatus (2010) are described below, it should be understood that the apparatus (2010) may be used in accordance with the description in U.S. Patent Application 14 / 619,256, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agents," filed on February 11, 2015, the disclosure of which is incorporated herein by reference. Similar to the apparatus (10), the apparatus (2010) of this example may generally be used in the procedures described herein to deliver therapeutic fluids to the patient's eye subretinaly from a suprachoroidal approach. It should therefore be understood that the apparatus (2010) may be readily used in place of the apparatus (10) to perform the medical procedures described herein. Similar to the apparatus (10), the apparatus (2010) of this example includes a cannula (20), a body (2040), and an actuation assembly (2100). Cannula (20) includes a nitinol needle (2030) extending therethrough (shown in Figure 20 to Figure 21 , Fig. 23B , FIG. 26B to FIG. 26C and Fig.27B In the present example, cannula (20) and needle (2030) are substantially the same as cannula (20) and needle (30) described above.

[0086] The primary difference between instrument (10) and instrument (2010) is that 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 needle (2030). Actuation assembly (2100) is generally operable to longitudinally translate the valve assembly via rotation of knob member (2110), thereby longitudinally translating needle (2030) relative to cannula (20).

[0087] When the actuation assembly (2100) is in the proximal position, the operator may rotate the knob member (2110) in a counterclockwise or clockwise direction. If the knob member (2110) is rotated in a counterclockwise direction, the rotation member (2110) will only rotate freely. To begin advancement of the actuation assembly (2100), the valve assembly, and the needle (2030), the operator may rotate the knob member (2110) in a clockwise direction. The clockwise rotation of the knob member (2110) will act to translate the knob member (2110) distally and will also act to translate the valve assembly and the needle (2030) distally. The operator may continue to rotate the knob member (2110) clockwise to drive the needle (2030) away from the distal end of the cannula (20) such that the distal end (2032) of the needle (2030) is located distal to the distal end of the cannula (20).

[0088] Once needle (2030) has been advanced to its most distal position relative to the distal end of cannula (20), further clockwise rotation of knob member (2110) will simply result in free rotation of knob member (2110) due to slippage of the clutch feature incorporated into actuation assembly (2100). When needle (2030) is in the distal position, the operator can actuate the valve assembly to enable delivery of a therapeutic agent via lumen (2034) of needle (2030), as described in detail below.

[0089] After delivering the therapeutic agent, the operator may then wish to retract the needle (2030). Counterclockwise rotation of the knob member (2110) will cause the actuation assembly (2100), the valve assembly, and the needle (2030) 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 the needle (2030), the valve assembly and the needle (2030) remain substantially rotationally fixed relative to the body (2040). It should also be understood that although the rotating member (2110) of the present example is described as being 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 (2030) 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. Additionally or alternatively, such servo controllers may be operated via a computer that takes action based on feedback from the instrument (2010) or any other component described herein.

[0090] III. Exemplary Suture Measurement Template

[0091] Figure 8 An exemplary suture measurement template (210) is shown that can be used in a process of providing subretinal delivery of a therapeutic agent from a suprachoroidal approach, as will be described in more detail below. In general, the template (210) is configured to be pressed against a patient's eye to imprint a specific pigment pattern onto the patient's eye. It should be understood that references herein to pressing the template (210) against the patient's eye may include, but are not necessarily limited to pressing the template (210) directly against the surface of the sclera (304) (e.g., after the conjunctiva has been removed or otherwise displaced). The template (210) includes a rigid body (220) and a rigid shaft (240). As will be described in more detail below, the body (220) is generally contoured to correspond to the curvature of the patient's eye so that the body (220) can be pressed or placed onto at least a portion of the patient's eye. The body (220) includes an upper guide portion (222) and a plurality of protrusions (230) extending distally from an ocular surface (224) of the body (220).

[0092] The upper guide portion (222) is generally semicircular in shape and is disposed at the top of the body (220). The semicircular shape of the upper guide portion (222) has a radius corresponding to the curvature of the corneoscleral limbus of the patient's eye. In other words, the upper guide portion (222) curves proximally along a first radius corresponding to the radius of curvature of the patient's eyeball; and curves downward (toward the longitudinal axis of the shaft (240)) along a second radius corresponding to the radius of curvature of the corneoscleral 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 corneoscleral limbus of the patient's eye. Therefore, any coloring that can be deposited onto the patient's eye via the template can be positioned relative to the corneoscleral limbus of the patient's eye.

[0093] The protrusion (230) is spaced apart from the upper guide portion (222) by a predetermined distance. Specifically, the protrusion (230) forms a pattern that may correspond to a relevant mark used during the method described below. The protrusion (230) of this example includes 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 outwardly from the body (220) by an equal distance, so that the protrusions (230) jointly maintain the curvature defined by the body (220). In other words, the ends of the protrusions (230a-230j) are all located on a curved plane defined by the following radius of curvature, which is complementary to the radius of curvature of the patient's eyeball. The tips of the protrusions (230a-230j) are rounded and atraumatic so that the protrusions (230a-230j) can be pressed against the eye without damaging the sclera or other parts of the patient's eye.

[0094] The 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 the present example, the shaft (240) is integral with the body (220). In other examples, the shaft (240) may be selectively attached to the body by a mechanical fastening device (such as a threaded connector or a mechanical fastener, etc.). In some versions, a kit including a shaft (240) and a plurality of bodies (220) may be presented to the operator. The body (220) may have different curvatures to correspond to different eyeballs having different radii of curvature. The operator may therefore select an appropriate body (220) from the kit based on the anatomy of the particular patient in front of the operator; and the operator may then secure the selected body (220) to the shaft (240). Although not shown, it should be appreciated that the proximal end of shaft (240) may additionally include a t-grip, knob, or other gripping feature to allow an operator to more easily grip shaft (240).

[0095] In an 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 can 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). Once the protrusion (230) has received the pigment or ink, the operator can mark the patient's eye by pressing the protrusion (230) of the template (210) onto the patient's eye, as will be described in more detail below. Once the template (210) is removed from the patient's eye, the pigment from the protrusion can remain attached to the eye to mark a specific point of interest, as will be described in more detail below.

[0096] IV. Exemplary Methods for Subretinal Delivery of Therapeutic Agents via the Suprachoroidal Route .

[0097] Figures 9A-11C An exemplary process for subretinal delivery of a therapeutic agent from a suprachoroidal approach utilizing the apparatus (10) described above is shown. However, it should be understood that the apparatus (2010) may be readily combined with or substituted for the apparatus (10) for use in the processes described below. By way of example only, the methods described herein may be used to treat macular degeneration and / or other ocular conditions. Although the processes described herein are discussed in the context of treatment of age-related macular degeneration, it should be understood that such limitations are not intended or implied. For example, in some merely exemplary alternative processes, the same techniques described herein may be used to treat retinitis pigmentosa, diabetic retinopathy, and / or other ocular conditions. In addition, it should be understood that the processes described herein may be used to treat dry or wet age-related macular degeneration.

[0098] As in Fig. 9A As can be seen in , the procedure begins with the operator securing tissue (e.g., eyelid) surrounding the patient's eye (301) using a speculum (312) and / or any other instrument suitable for securing. Although securement is described herein with reference to tissue surrounding the eye (301), it should be understood that the eye (301) itself may remain free to move. Once the tissue surrounding the eye (301) has been secured, an eye chandelier port (314) is inserted into the eye (301) to provide intraocular illumination while observing the interior of the eye (301) through the pupil. In this example, the eye chandelier port (314) is positioned in the inferior medial quadrant so that a superior temporal quadrant sclerotomy can be performed. As shown in Fig. 10AAs can be seen in FIG, 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 such illumination corresponds to the area of ​​the eye (301) to which the therapeutic agent is intended to be delivered. In the present example, only the chandelier port (314) is inserted at this stage, without inserting the optical fiber (315) into the port (314). In some other versions, the optical fiber (315) may be inserted into the chandelier port (314) at this stage. In either case, a microscope may optionally be used to visually inspect the eye to confirm the proper positioning of the eye chandelier port (314) relative to the target site. Although Fig. 9A A particular positioning of eye chandelier port (314) is shown, but it should be understood that eye chandelier port (314) may have any other positioning, as would be apparent to one of ordinary skill in the art in view of the teachings herein.

[0099] Once the eye chandelier port (314) has been positioned, the conjunctiva may be peeled off by cutting a flap in the conjunctiva and pulling the flap posteriorly, thereby accessing the sclera (304). After such peeling is completed, the exposed surface (305) of the sclera (304) may optionally be bleached using a cautery tool to minimize bleeding. Once the conjunctival peeling is completed, the exposed surface (305) of the sclera (304) may optionally be dried using a WECK-CEL or other suitable absorbent device. The eye (301) may then be marked using the template (210) described above. As in Fig. 9B As can be seen in FIG. 1 , the template (210) is positioned to align with the corneoscleral limbus of the eye (301). The operator may apply light force to the template (210) to apply the pigment to the eye (301). The template (210) is then removed, thereby leaving the pigment attached to the exposed surface (305) of the sclera (304), thereby providing a visual guide (320) for the operator, as shown in FIG. Fig. 9C The operator can then use the visual guide (320) to attach the suture loop assembly (330) and perform a 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).

[0100] Fig.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 the sclerotomy and into the eye (301). Fig.9DAn exemplary process of the suture loop assembly (330) shown is described in U.S. Patent Application No. 14 / 619,256, filed on 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). As in Fig.9E As can be seen in FIG, the eye (301) is cut between the sclerotomy markers (329) using a conventional surgical scalpel (313) or other suitable cutting instrument. Although the sclerotomy markers (329) are shown as comprising two discrete dots, it should be understood that in other examples, the markers (329) may include any other type of marker, such as a solid line, a dotted line, or a dashed line. The sclerotomy procedure forms a small incision (316) through the sclera (304) of the eye (301). As shown in FIG. Fig. 10B As best seen in the eye (301), the sclerotomy is performed with particular care to avoid penetration of the choroid (306). Thus, the sclerotomy procedure provides access to the space between the sclera (304) and the choroid (306). Once the incision (316) is made in the eye (301), a blunt dissection may optionally be performed to locally separate the sclera (304) from the choroid (306). Such dissection may be performed using a small, blunt, elongated instrument, as will be apparent to one of ordinary skill in the art in view of the teachings herein.

[0101] In the event that a sclerotomy procedure has been performed, the operator may insert the cannula (20) of the instrument (10) through the incision (316) into the space between the sclera (304) and the choroid (306). Fig.9FAs can be seen in the figure, the guide cannula (20) passes through the guide collar (336) of the suture loop assembly (330) and enters the incision (316). As described above, the guide collar (336) can stabilize the cannula (20). In addition, the guide collar (336) keeps the cannula (20) in a generally tangential orientation relative to the incision (316). Such a tangential orientation can reduce trauma when the cannula (20) is guided through the incision (316) to stabilize the cannula (20) and avoid damaging surrounding tissue. When the cannula (20) is inserted into the incision (316) through the guide collar (336), the operator can 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 only optional and can 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 the surface of the cannula (20) to indicate various insertion depths. Although merely optional, such markers may be advantageous to help identify the correct insertion depth when guiding cannula (20) along an atraumatic path. For example, an operator may visually observe the position of such markers relative to guide collar (336) and / or relative to incision (316) as an indication of the depth of insertion of cannula (20) into eye (301). By way of example only, one such marker may correspond to an insertion depth of approximately 6 mm for cannula (20).

[0102] Once the cannula (20) is at least partially inserted into the eye (301), the operator may 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) held in place and fitted with the optical fiber (315), the operator may activate the eye chandelier port (314) by directing light through the optical fiber (315) to provide illumination of the eye (301) and thereby visualize the interior of the eye (301). Further adjustments may optionally be made to the positioning of the cannula (20) at this time to ensure proper positioning of the geographic atrophy region relative to the retina (308). In some cases, the operator may wish to rotate the eye (301), such as by pulling on the sutures (334, 339), to direct the pupil of the eye (301) toward the operator in order to optimize visualization of the interior of the eye (301) through the pupil.

[0103] Figure 9G and Figures 10C-10D A cannula (20) is shown being guided between the sclera (304) and the choroid (306) to a delivery site for a therapeutic agent. In this example, the delivery site corresponds to a generally posterior region of the eye (301) near an area of ​​geographic atrophy of the retina (308). Specifically, the delivery site of this example is located superior to the macula, in the potential space between the neurosensory retina and the retinal pigment epithelial cell layer. Figure 9G The eye (301) is shown under direct visualization by a microscope directed through the pupil of the eye (301), with illumination provided by optical fiber (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). Thus, the operator can move the cannula (20) from Fig. 10C The position shown is advanced through the eye (301) to Fig. 10D In versions where optical fiber (34) is used to transmit visible light through the distal end of cannula (20), such tracking may be enhanced.

[0104] Once the cannula (20) has been advanced to Fig. 10D The operator may then advance the needle (30) of the device (10) as described above with respect to the delivery site shown. Figure 3-Figure 4 As stated in FIG. 9H to FIG. 9I , Fig. 10E and Fig.11A As can be seen in FIG, needle (30) is advanced relative to cannula (20) such that needle (30) punctures choroid (306) without penetrating retina (308). Just prior to penetrating choroid (306), needle (30) may appear under direct visualization to "tent over" the surface of choroid (306), as shown in FIG. Figure 9H . In other words, the needle (30) may deform the choroid (306) by pushing upward on the choroid, thereby providing an appearance that is similar to a tent pole deforming the top of a tent. An operator may use such visual phenomena to identify whether the choroid (306) is about to be punctured and the location of any eventual puncture. The specific amount of needle (30) advancement sufficient to induce "tent-like covering" of the choroid (306) and subsequent puncture may be any suitable amount that may be determined by a variety of factors, such as, but not limited to, general patient anatomy, local patient anatomy, operator preference, and / or other factors. As described above, a merely 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.

[0105] In this example, after the operator has confirmed that needle (30) has been properly advanced by observing the tenting effect described above, the operator injects a balanced salt solution (BSS) or other similar solution as needle (30) is advanced relative to cannula (20). Such a BSS solution may form a pilot bubble (340) ahead of needle (30) as needle (30) is advanced through choroid (306). Pilot bubble (340) may be advantageous for two reasons. First, as Fig.9I , Fig.10F and Fig. 11BAs shown, the pilot bubble (340) can provide an additional visual indicator to the operator to indicate when the needle (30) is properly positioned at the delivery site. Second, the pilot bubble (340) can provide a barrier between the needle (30) and the retina (308) once the needle (30) has penetrated the choroid (306). Such a barrier can push the retinal wall outward (e.g., Fig.10F and 11B 30), thereby minimizing the risk of retinal perforation when needle (30) is advanced to the delivery site. In some versions, a foot switch is actuated to drive pilot bubble (340) out of needle (30). Alternatively, other suitable features that may be used to drive pilot bubble (340) out of needle (30) will be apparent to one of ordinary skill in the art in view of the teachings herein.

[0106] Once the operator observes the pilot bubble (340), the operator can stop injecting the BSS, leaving the Fig.9I , Fig.10F and Fig. 11B . Next, the therapeutic agent (341) may be injected by actuating a syringe or other fluid delivery device, as described above with respect to the apparatus (10). The specific therapeutic agent (341) delivered may be any suitable therapeutic agent configured to treat an ocular condition. Some merely exemplary suitable therapeutic agents may include, but are not necessarily limited to, drugs having smaller or larger molecules, therapeutic cell solutions, certain gene therapy solutions, and / or any other suitable therapeutic agent, which will be apparent to one of ordinary skill in the art with reference to the teachings herein. By way of example only, the therapeutic agent (341) may be provided in accordance with at least some of the teachings of the following patent: U.S. Patent No. 7,413,734, entitled “Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells,” filed on August 19, 2008, the disclosure of which is incorporated herein by reference.

[0107] In this example, the amount of therapeutic agent (341) ultimately delivered to the delivery site is approximately 50 μL, but any other suitable amount may be delivered. In some versions, a foot switch is actuated to drive agent (341) out of needle (30). Alternatively, other suitable features that may be used to drive agent (341) out of needle (30) will be apparent to one of ordinary skill in the art in view of the teachings herein. Delivery of the therapeutic agent may be visualized by inflation of the fluid bag, such as in FIG. Figure 9J , Figure 10G and Fig. 11CAs shown, when the therapeutic agent (341) is injected into the suprachoroidal space, the therapeutic agent (341) is substantially mixed with the fluid of the pilot bleb (340).

[0108] 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 appreciated that due to the size of the needle (20), the site where the needle (20) penetrates the choroid (306) is self-sealing, such that no additional steps need to be taken to seal the delivery site through the choroid (306). The suture loop assembly (330) and chandelier (314) can be removed, and the incision (316) in the sclera (304) can be closed using any suitable conventional technique.

[0109] 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 by the 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) can be provided according to at least some of the teachings of the following patent: U.S. Patent No. 7,413,734, entitled "Treatment of Retinitis Pigmentosa with Human Umbilical Cord Cells", filed on August 19, 2008, the disclosure of which is incorporated herein by reference. Alternatively, in addition to or in place of the substances described in U.S. Patent No. 7,413,734 and / or elsewhere herein, the needle (20) can be used to deliver any other suitable substance or substances. By way of example only, the therapeutic agent (341) can include various drugs, including but not limited to small molecules, macromolecules, cells, and / or gene therapies. It should also be understood that macular degeneration is only one merely illustrative example of a condition that can be treated by the process described herein. Other biological conditions that can be addressed using the devices and processes described herein will be apparent to those of ordinary skill in the art.

[0110] It should also be understood that the process described above can be in accordance with U.S. Patent Application No. 14 / 619,256, entitled "Method and Apparatus for Suprachoroidal Administration of Therapeutic Agents," filed on February 11, 2015, the disclosure of which is incorporated herein by reference. Similarly, the apparatus (10), apparatus (2010) can be configured in accordance with at least some of the teachings of U.S. Patent Application No. 14 / 619,256. Various suitable ways in which the teachings herein can be combined with the teachings of U.S. Patent Application No. 14 / 619,256 will be apparent to one of ordinary skill in the art.

[0111] V. Exemplary Suprachoroidal Sensing Systems

[0112] In some examples, it may be desirable to provide the device (10), device (2010) with features operable to indicate when the needle (30), needle (2030) has fully penetrated the choroid (306) so as to minimize the risk of the needle (30), needle (2030) puncturing the retina (308). Specifically, it may be desirable to provide features that provide an operator with real-time feedback indicating when the distal end (32) of the needle (30), needle (2030) has passed through Bruch's membrane (i.e., the innermost layer of the choroid (306)) and entered the subretinal space. As will be described in greater detail below, the device (10), device (2010) may include subsurface imaging technology operable to provide an operator with an image of tissue layers in the eye. Additionally or alternatively, the device (10), device (2010) may include a light-emitting feature operable to direct light through the retina (308) after penetrating the choroid (306). Instruments with 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 certain example variations are described herein, it should be understood that the instruments described herein may include any other alternative features that will be apparent to those of ordinary skill in the art in light of the teachings herein.

[0113] A. Exemplary Surgical System with Interferometer

[0114] Figures 12 to 24BAn exemplary surgical system (500) operable to perform the therapeutic agent delivery process described above is shown. The system (500) of this example includes an instrument (2010), an interferometer system (510), and a display (520). Although the system (500) will be described below as including the instrument (2010), it should be understood that the instrument (10) or other variations of the instrument (2010) may be readily used in place of the instrument (2010). In addition, although the system (500) of this example includes a display (520), it should be understood that the display (520) is merely optional and the instrument (2010) may be configured to provide visual and / or tactile feedback to the operator in addition to or in place of the display (520). For example, the instrument (2010) may be configured to provide visual and / or tactile feedback to the operator once the needle (2030) has penetrated the choroid (306) but before penetrating the retina (308).

[0115] As will be appreciated by one of ordinary skill in the art, and as will be described in greater detail below, the interferometer system (510) can be operated to obtain images of tissue layers within the eye. Specifically, the interferometer system (510) can be operated to provide an operator with an optical coherence tomography (OCT) scan showing sub-surface layers of the eye. The interferometer system (510) of the present example comprises a dispersive white light interferometer (D-WLI), but it will be appreciated that any other suitable interferometer may also be used, as will be apparent to one of ordinary skill in the art in view of the teachings herein. Fig.13 It shows how the interferometer system (510) is formed from several subsystems, each with its own set of components. Specifically, Fig.13 The interferometer system (510) of this example is shown to include a power source (530), a light source system (540), a position tracking system (550), a fiber optic assembly (560), a spectrometer (570), and an optical probe system (580). Although the interferometer system (510) is shown as being separate from and coupled to the instrument (2010), it should be understood that all or part of the interferometer system (510) may be incorporated into the instrument (2010). For example, in some variations, the power source (530) is separate from but coupled to the instrument (2010); while the remainder of the interferometer system (510) is directly incorporated into the instrument (2010).

[0116] The power supply (530) is operable to provide power to the interferometer system (510). Fig.14As shown, the power supply (530) of this example includes an AC / DC power supply (532) connected to an AC power grid (534) (e.g., via a conventional cable and wall outlet). The AC / DC power supply (532) is also connected to a connection and power distribution / adapter board (536) via a power connector (538). A power cable (710) extends from the power distribution / adapter board (536) to a light source system (540), as will be described in more detail below. The power supply (530) also includes a data acquisition board (537) and a line sensor board (539), both of which can be connected to external devices via corresponding USB connectors (533, 535). Of course, in addition to or in lieu of those described above, the power supply (530) may alternatively include any other suitable components or features.

[0117] like Fig.15 As shown, the light source system (540) of this example includes a driver (542). The driver (542) is connected to the connection of the power supply (530) via a cable (710) and a power distribution / adapter board (536), so that the power supply (530) can be operated to deliver power to the driver (542) via the cable (710). The driver (542) is electrically connected to the light source system (540) so that the driver (542) regulates the delivery of power to the power supply (544). In this example, the power supply (544) is operable to generate light in the near infrared (NIR) spectrum, but it should be understood that the power supply (544) can alternatively be configured to generate light at other locations along the spectrum. The power supply (544) is optically connected to an optical isolator (546) via an optical cable. The optical isolator (546) includes a conventional optical isolator that is operable to provide a one-way transmission of light from the power supply (544) to prevent light from being transmitted back to the power supply (544). The optical isolator (544) is also coupled to the fiber optic assembly (560) via an optical cable (720). Of course, the light source system (540) may alternatively include any other suitable components or features in addition to or in lieu of those described above.

[0118] The position tracking system (550) is also coupled to the cable (710) such that the position tracking system (550) also receives power from the power source (530) via the cable (710). Fig.16As shown, the position tracking system (550) also includes a driver (552). The driver (552) is connected to the power supply (530) and the power distribution / adapter board (536) via a cable (710). The position tracking system (550) also includes a tracking light source (554), which is connected to the driver (552) and powered by the driver (552). The tracking light source (554) is operable to generate light in the visible spectrum. However, it should be understood that the tracking light source (554) may alternatively be configured to generate light elsewhere along the spectrum. The tracking light source (554) is also connected to the fiber optic assembly (560) via an optical cable (730). Of course, in addition to or in lieu of those described above, the position tracking system (550) may alternatively include any other suitable components or features.

[0119] like Fig.17 As shown, the fiber assembly (560) includes a pair of optical connectors (561, 562). The optical connector (561) is connected to the cable (720) from the optical isolator (546) of the light source system (540). The optical connector (562) is connected to the cable (730) from the tracking light source (554) of the position tracking system (550). The optical connector (561) is also connected to the optical circulator (563). The optical output cable (740) is also connected to the optical circulator (563) to lead to the spectrometer (570), as will be described in more detail below. The optical connector (562) and the optical circulator (563) are connected to the fiber coupler (564).

[0120] The fiber coupler (564) is also connected to a beam collimator (565) and an optical cable (750) leading to an optical probe system (580), as will be described in more detail below. The beam collimator (565) is operable to project light toward an adjustable optical delay line (566). In this example, a portion of the adjustable optical delay line (566) can be manually moved toward and away from the beam collimator (565) to selectively adjust the delay. Specifically, the delay line (556) is adjusted to scan the interferometer path length in order to tune the signal. In some versions, the fiber assembly (560) has two optical rays (one used as a reference and the other for measurement). Optimal quality or strength can be achieved when these two lines have the same (precise) optical path length. However, when there are several interfaces on the measurement line side, it may not be guaranteed that any of these interfaces are exactly at a position equal to the reference line path. Thus, in this example, the operator can change the reference line (which is provided by the optical delay line (566)) to adjust the reference line length so that it will be exactly the sample length of the target interface. In this way, the operator can tune precisely on the desired interface rather than having a general field of view. Of course, the fiber optic assembly (560) may alternatively include any other suitable components or features in addition to or in lieu of those described above.

[0121] like Fig.18 As shown, the spectrometer (570) also includes a beam collimator (572) connected to the cable (740) from the circulator (563) of the fiber optic assembly (560). The beam collimator (572) is operable to project light toward a grating (574), which in turn splits (or diffracts) the light toward a lens (576). The light passes through the lens (576) toward an optical sensor (578). By way of example only, the optical sensor (578) may include a CCD sensor, a CMOS sensor, and / or any other suitable type of optical sensor. The optical sensor (578) is connected to the line sensor board (539) of the power supply (530) via the power cable (760), so that the optical sensor (578) receives power from the power supply (530) via the cable (760). The cable (760) is also configured to transmit data from the optical sensor (578) to the power supply (530) so that the data can be received and processed by the data acquisition board (537) as described below. Of course, the spectrometer (570) may alternatively include any other suitable components or features in addition to or in lieu of those described above.

[0122] like Fig.19As shown, the optical probe system (580) includes an optical connector (586) coupled to the optical fiber (750) of the optical fiber assembly (560). The optical connector (586) is also coupled to the optical probe (582) via an optical fiber (584). By way of example only, the optical fiber (584) may include a light-conducting flexible fused silica capillary having a core of approximately 150 μm, a cladding of approximately 165 μm, and a buffer layer of approximately 195 μm. Alternatively, the optical fiber (584) may have any other suitable configuration.

[0123] like Fig. 20 and Fig.21 As shown, the optical probe (582) is coupled to the distal end (2032) of the needle (2030) via an adhesive layer (583), such that the optical probe (582) is configured to translate simultaneously with and further with the needle (2030) in the interior lumen (84) of the needle guide (80) as the needle (2030) is guided out of the cannula (20) along the exit axis (Ea) as the needle (2030) penetrates the choroid (306). It should be understood that any suitable structure or technique may be used to secure the optical probe (582) to the needle (2030), including but not limited to epoxy, clamps, etc. The optical probe (582) of this example is oriented substantially parallel to the needle (2030) and is positioned adjacent to the outer surface of the needle (2030). Alternatively, the optical probe (582) may be positioned adjacent to the outer surface of the needle (2030) at any other suitable location. For example, optical probe (582) may be positioned adjacent to an outer top or outer bottom surface of needle (2030).

[0124] As yet another merely illustrative example, the optical probe (582) may be positioned within the lumen (2034) of the needle (2030), wherein the distal end of the optical probe (582) is longitudinally positioned to coincide with the longitudinal position of the distal end (2032) of the needle (2030). In some such configurations, the inner diameter of the lumen (2034) is substantially greater than the outer diameter of the optical probe (582) such that when the optical probe (582) is positioned within the lumen (2034), the pilot bubble (340) and the therapeutic agent (341) may flow through the optical probe (582) and exit the distal end (2032). The lumen (2034) may thus be coupled to a fluid-optical interface that enables both fluid (e.g., fluid for the pilot bubble (340) and the therapeutic agent (341)) and the optical probe (582) to be communicated through the lumen (2034). Various suitable forms that such a fluid-optical interface may take will be apparent to those of ordinary skill in the art in view of the teachings herein.In some other versions, optical probe (582) is removed from lumen (2034) prior to delivering pilot bubble (340) and therapeutic agent (341) through lumen (2034).

[0125] As in Fig.21 As best seen in FIG. 1 , in this example, optical probe (582) is laterally offset from needle (2030) such that there is a gap between the outer surface of optical probe (582) and the outer surface of needle (2030) into which adhesive layer (583) may be positioned. Such gap may have a thickness between 5-50 microns. Alternatively, optical probe (582) and needle (2030) may abut one another. Furthermore, optical probe (582) of this example is positioned relative to needle (2030) such that the distal end of optical probe (582) is positioned proximal to the distal end of needle (2030). However, optical probe (582) may be positioned at any suitable location along the length of needle (2030).

[0126] like Fig. 22 As shown, the optical probe (582) includes a gradient refractive index (GRIN) lens (590), a ferrule (594), and a protective ferrule (596). The optical fiber (584) passes through the ferrule (594) and projects the light beam (592) through the GRIN lens (590). The protective ferrule (596) is positioned around the GRIN lens (590) and the ferrule (594) to prevent damage to the optical probe (582). In some versions, the length of the optical probe (582) may be in the range of about 1.2 mm to 2.0 mm and the diameter may be about 250 μm. The length of the GRIN lens (590) may be in the range of about 0.6 mm to 1.0 mm and the diameter may be about 250 μm. The length of the ferrule (594) may be in the range of about 0.6 mm to 1.0 mm and the diameter may be about 250 μm. In some versions, the thickness of adhesive layer (583) may be in the range of about 5 μm and 50 μm, thereby producing an effective diameter around optical probe (582) in the range of about 260 μm to 350 μm. Of course, any other suitable dimensions may be used for any of these components. For example, some versions of optical probe (582) may have an effective diameter less than or equal to about 250 μm. Such smaller diameters may be preferred in versions in which optical probe (582) is inserted into lumen (2034) of needle (2030).

[0127] From the above, it should be understood that the optical probe (582) can be used to project light from the power source (544), the light source (554) and receive light backscattered and reflected from the tissue layer in front of the optical probe (582). The backscattered and reflected light can be collected by the optical sensor (578) of the spectrometer (570). The corresponding data from the optical sensor (578) can then be transmitted to the data acquisition board (537). It should be understood that different layers of the eye can provide different corresponding opacities. These different opacities can provide a series of corresponding peaks in a graph that plots the brightness change (ΔL) of the backscattered or reflected light along the line of sight of the optical probe (582). In other words, the peaks of brightness change (ΔL) can represent different tissue layers in the eye. The data acquisition board (537) can provide data from the optical sensor (578) to various components that process the data to present an optical coherence tomography (OCT) image in real time via the display (520) as described below. Various suitable hardware components and software algorithms that may be used to convert data from interferometer system (510) into optical coherence tomography (OCT) images in real time via display (520) will be apparent to those of ordinary skill in the art in view of the teachings herein. It should also be understood that display (520) may be provided by a piece of custom capital equipment, a conventional video monitor, a conventional tablet computer, and / or any other suitable device.

[0128] like Fig.23A As shown, when the cannula (20) is positioned at the delivery site between the sclera (304) and the choroid (306), the needle (2030) and the optical probe (582) are disposed within the distal end of the cannula (20) so that the optical probe (582) projects a light beam (592) through the choroid (306), the retina (308), and into the vitreous region (310) of the eye to produce a Fig.24A 520 . From this image, the operator can conclude that choroid ( 306 ) has not been punctured because choroid ( 306 ) is still visible on display ( 520 ). In other words, choroid ( 306 ) is still distal to the distal end of needle ( 2030 ) and optical probe ( 582 ). Fig. 23BAs shown, the needle (2030) and the optical probe (582) are advanced relative to the cannula (20) so that the needle (2030) and the optical probe (582) puncture the choroid (306) without penetrating the retina (308). From this image, the operator can visually observe through the display (520) that the choroid (306) has been punctured because the choroid (306) has almost disappeared from the display (520). As described above, the optical probe (582) of this example is positioned relative to the needle (2030) so that the distal end of the optical probe (582) is positioned proximally relative to the distal end of the needle (2030). The interferometer system (510) can be configured to account for this offset of the optical probe (582) relative to the distal end of the needle (2030) in order to provide an accurate determination of when the distal end of the needle (2030) has penetrated the choroid (306) and reached the subretinal space directly below the choroid (306).

[0129] In some versions, the instrument (2010) may be configured to provide visual, auditory, and / or tactile feedback to the operator to alert the operator that the choroid (306) has been punctured. For example, in some versions of the instrument (2010), a computer system (not shown) may receive and process data from the interferometer system (510). Such a computer system may be present as an external component relative to the instrument (2010), or may be an internal component of the instrument (2010). Such a computer system may be configured to alert the user in response to a change in brightness caused by the penetration of the choroid (306), thereby alerting the user that the needle (2030) has reached the subretinal space directly below the choroid (306). Such an alert may be auditory (e.g., a single beep or a series of beeps), tactile (e.g., a slight vibration of the instrument (2010)), or visual. For example, the instrument (2010) may include a single light or a series of lights that are configured to illuminate or change color in response to a change in brightness as described above. Additionally or alternatively, such a light may change color (e.g., from green to red) or change intensity (e.g., from dark to light) when the needle (2030) penetrates the choroid (306). Additionally or alternatively, the optical probe (582) may be configured to illuminate or change color in response to changes in brightness as described above. Additionally or alternatively, the optical probe (582) may change color (e.g., from green to red) or change intensity (e.g., from dark to light) when the needle (2030) penetrates the choroid (306). In some cases, the operator may prefer to receive notifications from the instrument (2010) in an auditory and / or tactile / tactile form. This may enable the operator to maintain observation through a microscope or other instrument used to provide observation of the retina (308), etc., without requiring the operator to divert their observation from the microscope or other observation instrument in order to receive notifications from the instrument (2010).

[0130] Once the operator has been notified that the choroid (306) has been punctured, such that the distal end of the needle (2030) has passed through Bruch's membrane and entered the subretinal space, the operator can immediately stop advancement of the needle (2030) and subsequently administer the pilot blister (340) and therapeutic agent (341) in accordance with the teachings herein. Other suitable ways in which the interferometer system (510) and display (520) may be used in conjunction with the apparatus (2010) will be apparent to those of ordinary skill in the art in view of the teachings herein.

[0131] B. Exemplary Surgical System with Microscope Imaging Detector

[0132] Figures 25 to 27B Another exemplary surgical system (600) that can be used to perform the therapeutic agent delivery process described above is shown. The system (600) of this example includes an instrument (2010), a microscope (610), a computer (620), a servo controller (630), a modulator (640), and a light source (650). Although the system (600) will be described below as including the instrument (2010), it should be understood that the instrument (10) or other variations of the instrument (2010) can be easily used in place of the instrument (2010).

[0133] like Fig.25 As shown, the instrument (2010) is connected to a light source (650) and a servo controller (630). As will be described in more detail below, the light source (650) includes a fiber optic cable (652) that is coupled to the needle (2030) such that the fiber optic cable (652) is operable to translate simultaneously with the needle (2030). As will also be described in more detail below, the light source (650) is operable to project light from the distal end of the needle (2030) into the eye via the fiber optic cable (652). The light source (650) of the present example is operable to generate visible light (i.e., having a wavelength between about 430 nm and 700 nm, or more specifically, having a wavelength between about 500 nm and 600 nm), infrared light (i.e., having a wavelength greater than about 700 nm), and / or near infrared light. In some versions, the light source (650) provides light having a wavelength of about 635 nm. The light source (650) is coupled to a modulator (640) configured to modulate the light provided by the light source (650). In some variations, the light source (650) comprises a laser. Other suitable forms that the light source (650) may take will be apparent to one of ordinary skill in the art in view of the teachings herein.

[0134] Servo controller (630) can be operable to control a servomotor (not shown). As described above, such a servomotor can be operable to supplement or replace the translation of the rotation member (2110) to drive the needle (2030). Various suitable components and features that can be used to provide actuation of the needle (2030) under the control of the servo controller (630) will be apparent to one of ordinary skill in the art in view of the teachings herein. It should also be understood that the needle (2030) can be manually driven instead (e.g., via a slider, via screw advancement, etc.), such that the servomotor (630) and servomotor can be omitted if desired.

[0135] The servo controller (630) and the modulator (640) are connected to the computer (620) so that the computer (620) is operable to execute a control algorithm to drive both the servo controller (630) and the modulator (640). The computer (620) is connected to a camera (613), which is coupled to the microscope (610). As will be described in more detail below, the computer (620) is operable to control the servo controller (630), the servo motor, the modulator (640), and the light source (650) based on feedback from the camera (613). Also as will be described in more detail below, the microscope (610) is operable to detect light emitted from the light source (650) through the vitreous region (310), thereby indicating when the needle (2030) has completely penetrated the choroid (306).

[0136] like Fig.25 As shown, a microscope (610) is positioned adjacent to the cornea (350) of an eye so that the microscope (610) is operable to detect light projected from the vitreous region (310) and through the pupil (352) of the eye. The light projected from the vitreous region (310) and through the pupil (352) of the eye is configured to pass through an aspheric lens (604) so ​​as to reduce or eliminate optical aberrations within the light. A light source (602) is configured to project visible light to provide illumination of the vitreous region (310) of the eye. Visible light from the light source (602) passes through a beam splitter (606) that redirects the light to be projected through the pupil (352) into the vitreous region (310) of the eye. The beam splitter (606) further allows light projected back from the eye to pass through the beam splitter (606) to reach the microscope (610).

[0137] The microscope (610) of this example includes a series of lenses (611) operable to provide magnification. The microscope (610) also includes a dichroic beam splitter (612) operable to separate light. Specifically, the dichroic beam splitter (612) is operable to separate light in the visible spectrum (VIS) from light in the infrared spectrum (IR). Once separated, this VIS light passes through one or more lenses (611) within the microscope (610) and then through a filter (614) to enable visualization by the user's naked eye at a port (615); while the IR light passes through a camera (613). The camera (613) includes one or more lenses (617) through which the IR light passes, so as to focus the IR light from the dichroic beam splitter (612). The focused IR light is then passed to an IR image sensor (616) of the camera (613). The image sensor (616) of this example may be a charge coupled device (CCD) image sensor, a complementary metal oxide semiconductor (CMOS) image sensor, or any other suitable type of image sensor. In some versions, image sensor (616) is operatively configured to capture images at a rate of 300 frames per second. This may provide a spatial resolution of approximately 1 μm when needle (2030) is advanced at a penetration speed of approximately 300 μm / s. Alternatively, any other suitable frame rate may be used for image sensor (616); and any other suitable penetration speed may be used for needle (2030).

[0138] like Fig.26A and Fig.27A As shown, the cannula (20) is positioned between the sclera (304) and the choroid (306). In this position, the needle (2030) and the fiber optic cable (652) are disposed within the distal end of the cannula (20) so that the fiber optic cable (652) projects light (654) into the choroid (306). Due to the relatively opaque nature of the choroid (306), the light (654) from the fiber optic cable (652) does not pass through the choroid (306) into the retina (308) and vitreous region (310). Therefore, at this point, the light (654) from the fiber optic cable (652) is not visible or detectable via the image sensor (616); or it may be partially detectable but weak.

[0139] like Fig.26BAs shown, the needle (2030) and fiber optic cable (652) are advanced relative to the cannula (20) such that the needle (2030) and fiber optic cable (652) partially puncture the choroid (306). In this position, the distal end (2032) of the needle (2030) and the fiber optic cable (652) are partially exposed relative to the distal end of the cannula (20), such that the fiber optic cable (652) projects light (654) into the choroid (306). Again, due to the relatively opaque nature of the choroid (306), the light (654) from the fiber optic cable (652) does not completely pass through the choroid (306) into the retina (308) and vitreous region (310). Thus, at this point, while some light (654) from the fiber optic cable (652) is visible or detectable via the image sensor (616) of the camera (613), the light is not intense enough to exceed the threshold associated with the fiber optic cable (652) reaching the subretinal space beyond the choroid (306).

[0140] like Fig.26C and Fig.27B As shown, the needle (2030) and fiber optic cable (652) are further advanced relative to the cannula (20) such that the needle (2030) and fiber optic cable (652) completely puncture the choroid (306) without penetrating the retina (308). At this position, the fiber optic cable (652) projects light (654) into the retina (308). Due to the relatively opaque nature of the choroid (308), the light (654) from the fiber optic cable (652) passes through the retina (308) and enters the vitreous region (310). Therefore, at this point, the light (654) from the fiber optic cable (652) is visible and / or detectable via the image sensor (616) at an intensity associated with the distal end (2032) of the needle (2030) and the fiber optic cable (652) reaching the subretinal space above the choroid (306).

[0141] Once the image sensor (616) detects light (654) exceeding a threshold intensity associated with the distal end (2032) of the needle (2030) and the fiber optic cable (652) reaching the subretinal space above the choroid (306), the computer (620) may stop the servo motor to prevent further translation of the needle (2030) and the fiber optic cable (652). Additionally or alternatively, once the image sensor (616) detects light (654) exceeding a threshold intensity associated with the distal end (2032) of the needle (2030) and the fiber optic cable (652) reaching the subretinal space above the choroid (306), the instrument (2010) may provide an audible, tactile, and / or visual signal to the operator to indicate that the subretinal space has been reached. As described above, the operator may prefer to receive notifications from the instrument (2010) in the form of audible and / or tactile / tactile sensations. This may enable the operator to maintain observation through a microscope or other instrument used to provide observation of the retina (308), etc., without requiring the operator to divert their observation from the microscope or other viewing instrument in order to receive notification from the instrument (2010). In versions where needle (2030) is advanced manually rather than via a servo motor, the operator may stop advancement of needle (2030) in response to an audible, tactile, and / or visual signal indicating that the subretinal space has been reached.

[0142] Regardless of how the operator is notified that the subretinal space has been reached, and regardless of how advancement of needle (2030) is actuated and stopped, the operator can then administer pilot bubble (340) and therapeutic agent (341) in the subretinal space in accordance with the teachings herein. Other suitable ways in which system (600) may be used in conjunction with apparatus (2010) will be apparent to those of ordinary skill in the art in view of the teachings herein.

[0143] It should be understood that as the distal end (2032) of the needle (2030) is advanced through the choroid (306), the intensity of the light received by the image sensor (616) increases. By way of example only, the highest jump in light intensity may occur once the distal end (2032) of the needle (2030) and the fiber optic cable (652) pass from below the retinal pigment epithelium (RPE) to above the RPE. In some cases, once the distal end (2032) of the needle (2030) and the fiber optic cable (652) penetrate the RPE, the light intensity may suddenly increase by about 20% to about 40%. The intensity of light received by the image sensor (616) may also vary based on the position of the distal end (2032) of the needle (2030) and the fiber optic cable (652) in the eye according to the teachings of Gao et al., “Measuring Retinal Contributions to the Optical Stiles-Crawford Effect with Optical Coherence Tomography,” published in OPTICS EXPRESS, 16.9 (2008): pp. 6486-6501, the disclosure of which is incorporated herein by reference.

[0144] VI. Exemplary Combinations

[0145] The following embodiments relate to various non-exhaustive ways in which the teachings of this article can be combined or applied. It should be understood that the following embodiments are not intended to limit the coverage of any claims that may be provided at any time in this patent application or in the subsequent submissions of this patent application. It is not intended to make a disclaimer. The following embodiments are provided for exemplary purposes only. It is conceivable that the various teachings of this article can be arranged and applied in a variety of other ways. It is also conceivable that some variations may omit some of the characteristic structures mentioned in the following embodiments. Therefore, any of the aspects or characteristic structures mentioned below should not be considered decisive, unless otherwise, for example, by the inventor or the successor of the inventor concerned clearly indicated at a later date. If any claim provided in this patent application or in the subsequent submissions related to this patent application includes additional characteristic structures other than those characteristic structures mentioned below, these additional characteristic structures should not be assumed to be added for any reason related to patentability.

[0146] Example 1

[0147] A system for delivering a therapeutic agent to an eye, wherein the system comprises: (a) a surgical instrument, wherein the surgical instrument comprises: (i) a body; (ii) a cannula extending distally from the body, wherein the cannula is sized and configured to be insertable between the choroid and the sclera of an eye of a patient, wherein the cannula defines a longitudinal axis; (iii) a hollow needle, wherein the needle is slidable relative to the cannula; and (iv) an actuation assembly, wherein the actuation assembly is operable to actuate the needle relative to the cannula to drive a distal portion of the needle along an exit axis; and (b) an interferometer system, wherein the interferometer system comprises an optical probe coupled to a distal end of the hollow needle such that the optical probe is operable to slide within the cannula simultaneously with the hollow needle, wherein the interferometer system is operable to provide data indicative of a position of the distal end of the hollow needle within the patient's eye.

[0148] Example 2

[0149] A system as described in embodiment 1, wherein the optical probe comprises a gradient refractive index (GRIN) lens.

[0150] Example 3

[0151] A system according to any one or more of embodiments 1-2, wherein the outlet axis is oriented obliquely relative to the longitudinal axis of the cannula.

[0152] Example 4

[0153] A system as described in any one or more of embodiments 1 to 3, wherein the interferometer system includes a spectrometer.

[0154] Example 5

[0155] A system according to any one or more of embodiments 1 to 4, wherein the interferometer system is operable to provide an operator with an optical coherence tomography (OCT) scan showing sub-surface layers of the eye.

[0156] Example 6

[0157]

[00136] The system of Example 5, wherein the system further comprises a display operable to display the OCT scan of the interferometer.

[0158] Example 7

[0159] A system as described in any one or more of embodiments 1 to 6, wherein the interferometer system includes a dispersive white light interferometer (D-WLI).

[0160] Example 8

[0161] A system according to any one or more of embodiments 1 to 7, wherein the interferometer system includes a display operable to show the choroid and retina of the patient's eye.

[0162] Example 9

[0163] A system according to any one or more of embodiments 1 to 8, wherein the optical probe of the interferometer system is coupled to the distal end of the hollow needle via an adhesive layer.

[0164] Example 10

[0165] The system of any one or more of embodiments 1-9, wherein the interferometer system is operable to provide visual feedback, auditory feedback, and / or tactile feedback to an operator.

[0166] Embodiment 11

[0167]

[00136] The system of Example 10, wherein the interferometer system is operable to provide visual feedback, auditory feedback, and / or tactile feedback to an operator in response to the hollow needle puncturing the choroid.

[0168] Example 12

[0169] The system of any one or more of embodiments 1-11, wherein the interferometer system comprises a position tracking system.

[0170] Example 13

[0171] A system according to any one or more of embodiments 1 to 12, wherein the optical probe is positioned proximally relative to the distal end of the needle.

[0172] Embodiment 14

[0173] A system according to any one or more of embodiments 1 to 13, wherein the optical probe is oriented substantially parallel to the needle.

[0174] Embodiment 15

[0175] A system according to any one or more of embodiments 1 to 14, wherein the optical probe is laterally offset from the needle.

[0176] Example 16

[0177] A system for delivering a therapeutic agent to an eye, wherein the system comprises: (a) a surgical instrument, wherein the surgical instrument comprises: (i) a body; (ii) a cannula extending distally from the body, wherein the cannula is sized and configured to be insertable between the choroid and the sclera of a patient's eye, wherein the cannula defines a longitudinal axis; (iii) a hollow needle, wherein the needle is slidable relative to the cannula; (iv) a light-emitting fiber optic cable, wherein the fiber optic cable is operable to emit light through the patient's eye; and (v) an actuation assembly, wherein the actuation assembly is operable to actuate the needle relative to the cannula to drive a distal portion of the needle along an exit axis; and (b) a microscopic imaging detector, wherein the microscopic imaging detector is operable to detect light emitted from the fiber optic cable through the patient's eye.

[0178] Embodiment 17

[0179] A system as in Example 16, wherein the fiber optic cable is coupled to a distal end of the needle such that the fiber optic cable is operable to slide within the cannula simultaneously with the needle.

[0180] Embodiment 18

[0181] A system according to any one or more of Examples 16 to 17, wherein one or both of the instrument or the microscope imaging detector includes a feedback feature structure operable to provide auditory feedback, tactile feedback, or visual feedback in response to the distal end of the needle reaching the space between the retina and choroid of the patient's eye based on light detected by the microscope imaging detector.

[0182] Embodiment 19

[0183] A system according to any one or more of Examples 16 to 18, wherein the actuation assembly includes a servo motor, wherein the servo motor is operable to actuate the needle relative to the cannula, wherein the actuation assembly further includes a servo controller in communication with the microscope imaging detector, wherein the servo controller is operable to control the servo motor based on light detected by the microscope imaging detector.

[0184] Embodiment 20

[0185] A system for delivering a therapeutic agent to an eye, wherein the system comprises: (a) a surgical instrument, wherein the surgical instrument comprises: (i) a body; (ii) a cannula extending distally from the body, wherein the cannula is sized and configured to be insertable between the choroid and the sclera of a patient's eye, wherein the cannula defines a longitudinal axis; (iii) a hollow needle, wherein the needle is slidable relative to the cannula; and (iv) an actuation assembly, wherein the actuation assembly is operable to actuate the needle relative to the cannula to drive a distal portion of the needle along an exit axis; and (b) a detection or visualization system, wherein a portion of the detection or visualization system is coupled to the distal end of the needle such that the detection or visualization system is operable to slide within the cannula simultaneously with the needle, wherein the detection or visualization system is operable to detect or visualize penetration of the choroid of the patient's eye.

[0186] VII. Miscellaneous

[0187] It should be understood that any type of apparatus described herein may also include various other features in addition to or as an alternative to those features described above. By way of example only, any device herein may also include one or more of the various features disclosed in any of the various references incorporated herein by reference.

[0188] It should be understood that any one or more of the teachings, expressions, implementations, examples, etc. described herein may be combined with any one or more of the other teachings, expressions, implementations, examples, etc. described herein. Therefore, the above teachings, expressions, implementations, examples, etc. should not be considered independent of each other. With reference to the teachings herein, various suitable ways in which the teachings herein can be combined will be apparent to those of ordinary skill in the art. Such modifications and variations are intended to be included within the scope of the claims.

[0189] It should be understood that any patent, publication or other public material, whether in whole or in part, allegedly incorporated herein by reference is incorporated herein only to the extent that the incorporated material does not conflict with the definitions, statements or other public materials given in the present disclosure. Likewise and to the extent necessary, the disclosure explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material or portion thereof allegedly incorporated herein but conflicting with existing definitions, statements or other public materials described herein is incorporated herein only to the extent that no conflict arises between the incorporated material and the existing public materials.

[0190] The above-described types can be designed to be discarded after a single use, or they can be designed to be used multiple times. In either case or both, the repairable type can be reused after at least one use. Repair may include any combination of the following steps: disassembling the device, then cleaning or replacing specific parts and subsequently reassembling. Specifically, some types of devices can be disassembled, and any number of specific parts or components of the device can be selectively replaced or removed in any combination. When cleaning and / or replacing specific parts, some types of the device can be reassembled at a repair facility or reassembled by the operator before surgery is about to be performed for subsequent use. Those skilled in the art will appreciate that the repair of the device can utilize a variety of techniques for disassembly, cleaning / replacement and reassembly. The use of these technologies and the resulting repair device are all within the scope of the present application.

[0191] By way of example only, the types described herein can be sterilized before and / or after surgery. In one sterilization technique, the device is placed in a closed and sealed container, such as a plastic bag or a TYVEK bag. The container and device can then be placed in a field of radiation that can penetrate the container, such as gamma radiation, X-rays, or high-energy electrons. The radiation can kill bacteria on the device and in the container. The sterilized device can then be stored in a sterile container for later use. The device can also be sterilized using any other technique known in the art, including but not limited to beta or gamma radiation, ethylene oxide, or steam.

[0192] Various embodiments of the present invention have been shown and described, and further improvements of the methods and systems described herein may be achieved by appropriate modifications by those of ordinary skill in the art without departing from the scope of the present invention. Several such potential modifications have been mentioned, and other modifications will be apparent to those of skill in the art. For example, the examples, embodiments, geometries, materials, dimensions, ratios, steps, etc. described above are exemplary and not required. Therefore, the scope of the present invention should be considered in light of the following claims, and should be understood not to be limited to the details of the structure and operation shown and described in the specification and drawings.

Claims

1. A system for delivering a therapeutic agent to an eye, wherein the system comprises: (a) A surgical instrument (10, 2010), wherein the surgical instrument comprises: (i) the subject (40, 2040), (ii) a flexible cannula (20, 2020) extending distally from the body, wherein the cannula is sized and configured to be insertable between the choroid and sclera of an eye of a patient, wherein the cannula defines a longitudinal axis, (iii) a hollow needle (30), wherein the needle is slidable relative to the cannula, and (iv) an actuation assembly, wherein the actuation assembly is operable to actuate the needle relative to the cannula to drive a distal portion of the needle along an exit axis that is oriented obliquely relative to a longitudinal axis of the cannula; and (b) a detection system, a portion of which is coupled to the distal end of the needle such that the detection system is operable to slide with the needle within the cannula, wherein the detection system is operable to detect penetration of the choroid of the patient's eye.

2. A system according to claim 1, wherein the detection system is an interferometer system (510), the interferometer system comprising an optical probe (582), wherein the optical probe is connected to the distal end of the hollow needle so that the optical probe is operable to slide simultaneously with the hollow needle within the cannula, and wherein the interferometer system is operable to provide data indicating the position of the distal end of the hollow needle within the patient's eye.

3. The system of claim 2, wherein the optical probe comprises a gradient refractive index (GRIN) lens.

4. The system of claim 2, wherein the interferometer system comprises a spectrometer.

5. The system of claim 2, wherein the interferometer system is operable to provide an operator with an optical coherence tomography (OCT) scan showing sub-surface layers of the eye.

6. The system of claim 5, wherein the system further comprises a display operable to show the OCT scan of the interferometer.

7. The system of claim 2, wherein the interferometer system comprises a dispersive white light interferometer (D-WLI).

8. The system of claim 2, wherein the interferometer system includes a display operable to show the choroid and retina of the patient's eye.

9. The system of claim 2, wherein the optical probe of the interferometer system is coupled to the distal end of the hollow needle via an adhesive layer.

10. The system of claim 2, wherein the interferometer system is operable to provide visual feedback, auditory feedback, and / or tactile feedback to an operator.

11. The system of claim 10, wherein the interferometer system is operable to provide visual feedback, auditory feedback, and / or tactile feedback to an operator in response to the hollow needle puncturing the choroid.

12. The system of claim 2, wherein the interferometer system comprises a position tracking system.

13. The system of claim 2, wherein the optical probe is positioned proximally relative to the distal end of the needle.

14. The system of claim 2, wherein the optical probe is oriented substantially parallel to the needle.

15. The system of claim 2, wherein the optical probe is laterally offset from the needle.

16. The system of claim 1, wherein the surgical instrument further comprises: a light emitting fiber optic cable (652), wherein the fiber optic cable is operable to transmit light through an eye of a patient, and Wherein the detection system is a microscopic imaging detector, wherein the microscopic imaging detector is operable to detect light emitted from the fiber optic cable through an eye of a patient.

17. The system of claim 16, wherein the fiber optic cable is coupled to a distal end of the needle such that the fiber optic cable is operable to slide within the cannula simultaneously with the needle.

18. A system according to claim 16, wherein one or both of the instrument or the microscope imaging detector includes a feedback feature structure that is operable to provide auditory feedback, tactile feedback, or visual feedback in response to the distal end of the needle reaching the space between the retina and choroid of the patient's eye based on light detected by the microscope imaging detector.

19. A system according to claim 16, wherein the actuation assembly includes a servo motor, wherein the servo motor is operable to actuate the needle relative to the cannula, wherein the actuation assembly further includes a servo controller in communication with the microscope imaging detector, wherein the servo controller is operable to control the servo motor based on light detected by the microscope imaging detector.

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