Systems and methods for drug delivery to ocular tissue

Abstract

To provide an improved apparatus for delivering medicament to a suprachoroidal space of an eye.SOLUTION: According to one aspect of the disclosure, an apparatus for manipulating a sclera to facilitate delivery of a medicament to a suprachoroidal space of an eye may include a needle with a sharp distalmost tip, a needle hub connected to a proximal end of the needle, a housing surrounding the needle hub and extending from a proximal end of the needle hub, and an adaptor surrounding a portion of the needle.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] Various aspects of the present disclosure relate generally to the delivery of drugs to ocular tissues. More particularly, the present disclosure relates to devices and related methods for delivering drugs to the suprachoroidal space of the eye. [Background technology]

[0002] Eye disorders and diseases lead to optic nerve damage and visual field loss.Medical, laser surgery, and / or open surgery are therapeutic interventions that can be used to reduce intraocular pressure, preserve the existing vision of the subject, and help slow the further progression of disorders and / or diseases.With regard to open surgery, instruments for performing surgical procedures, devices for delivering drug treatments, and methods enabled by such instruments are highly sought after to provide improved results to users and subjects. Summary of the Invention

[0003] According to one aspect of the present disclosure, a system for delivering a drug to the suprachoroidal space of an eye includes a needle having a passageway and a sharp distal-most tip, and a device configured to manipulate the sclera to enable delivery of the drug to the suprachoroidal space of the eye.

[0004] Various embodiments of the system may include one or more of the following aspects: the needle may be configured to deliver an agent to the suprachoroidal space of the eye; the sharp distal-most tip may include a plurality of openings, which may include a circular structure or a slot, or the plurality of openings are present around at least a portion of the circumference and length of the sharp distal-most tip; the device may be configured to deliver an agent to the suprachoroidal space of the eye; the device may be disposed within the needle passageway and be longitudinally translatable relative to the needle; the device may include a tubular shaft having a distal end, which tubular shaft comprises a rigid, semi-rigid, or flexible material; the distal end may include an atraumatic distal tip, which may include a plurality of openings, which may include a circular structure or a slot, or the plurality of openings are present around at least a portion of the circumference and length of the atraumatic distal tip. the distal end may include an expandable member, which may include a stent; the tubular shaft may include an expandable portion, which may include a pair of curved arms located proximal to the atraumatic distal tip; the tubular shaft may include a cross-sectional dimension smaller than a cross-sectional dimension of the passageway; the outer surface of the tubular shaft may include one or more channels; the distal end of the tubular shaft includes at least two legs configured to selectively diverge when the distal end of the tubular shaft is deployed from the needle passageway; the needle may be curved; the needle may be U-shaped; the needle may include a bend located proximal to the pointed distal-most tip; the needle may include an outer surface having a plurality of geometric features configured to provide tactile feedback to the user; or the distal end may include an anchor, which may have a curved, flat, or atraumatic shape.

[0005] In another embodiment, the system of the present disclosure can include a flat surface with protrusions for deforming one or more of the sclera or choroid, and the protrusions can be rounded. In another embodiment, the system of the present disclosure can include a chamber configured to retract a portion of the sclera, and the device can be configured to apply suction to the sclera; the needle can be disposed in the chamber; the chamber can include a stop configured to limit proximal advancement of the sclera into the chamber; the stop can be configured to surround the needle; the stop can include multiple extensions extending from the sidewall of the chamber toward the center of the chamber; the stop can include multiple openings configured to allow application of suction to the sclera; the chamber can include a circular cross-sectional structure; or the chamber can include a semicircular cross-sectional structure.

[0006] The present disclosure includes a device for treating the sclera to enable delivery of a drug to the suprachoroidal space of an eye, the device comprising a tubular shaft having a distal end, the tubular shaft comprising a rigid, semi-rigid, or flexible material, and a needle having a passageway and a sharp, distal-most tip, the device being disposed within the needle. Various embodiments of the device may include one or more of the following aspects: the needle may be configured to deliver a drug to the suprachoroidal space of the eye; the sharp, distal-most tip may include multiple openings, the openings may include a circular structure or slots, or the multiple openings are present around at least a portion of the circumference and length of the sharp, distal-most tip; the device may be configured to deliver a drug to the suprachoroidal space of the eye; the device may be longitudinally translatable relative to the needle; the distal end may include an atraumatic distal tip, the atraumatic distal tip may include multiple openings, the openings may include a circular structure or slots, or the multiple openings are present around the atraumatic distal tip. the distal end may include an expandable member, which may comprise a stent; the tubular shaft may include an expandable portion, which may comprise a pair of curved arms located proximal to the distal end; the tubular shaft may include a cross-sectional dimension smaller than the cross-sectional dimension of the passage; the outer surface of the tubular shaft may include one or more channels; the distal end of the tubular shaft includes at least two legs configured to selectively diverge when the distal end of the tubular shaft is deployed from the needle passage; the needle may be curved; or the distal end may include an anchor, which has a curved, flat, or atraumatic shape.

[0007] In another aspect, the present disclosure includes a device for manipulating the sclera to enable delivery of an agent to the suprachoroidal space of the eye, the device comprising a flat surface with protrusions for deforming one or more of the sclera or choroid, the protrusions may be rounded surfaces.

[0008] In another aspect, the present disclosure includes a device for treating the sclera to enable delivery of a drug to the suprachoroidal space of the eye, the device comprising a chamber configured to retract a portion of the sclera. Various embodiments of the device may include one or more of the following aspects: the device may be configured to apply suction to the sclera; the needle may be disposed within the chamber; the chamber may include a stop configured to prevent proximal advancement of the sclera into the chamber; the stop may be configured to surround the needle; the stop may include multiple extensions extending from the sidewall of the chamber toward the center of the chamber; the stop may include multiple openings configured to allow application of suction to the sclera; the chamber may include a circular cross-sectional structure; or the chamber may include a semicircular cross-sectional structure.

[0009] In another aspect, the present disclosure includes an apparatus for treating the sclera to enable delivery of an agent to the suprachoroidal space of the eye, the apparatus comprising a needle tube having a cylindrical shape and a serrated needle tip, the serrated needle capable of vibrating to cut open a portion of the sclera.

[0010] In another aspect, the present disclosure includes a device for treating the sclera to enable delivery of a medicament to the suprachoroidal space of an eye, the device comprising: a needle having a sharp distal-most tip; a needle hub connected to the proximal end of the needle; and a housing surrounding the needle hub and extending from the proximal end of the needle hub. Various embodiments of the device may include one or more of the following aspects: the housing may be cylindrical; the housing may include additional components selected from a syringe, a spring, a piston, a plunger rod, an indicator, a feedback mechanism, or combinations thereof; or a shaft surrounding a portion of the needle and extending from the distal end of the needle hub, the distal end of the shaft being angled to allow for angled insertion of the needle.

[0011] In another aspect, the present disclosure is directed to a method for delivering a drug to the suprachoroidal space of an eye, the method comprising treating one of the sclera and choroid layers of the eye to increase the size of the suprachoroidal space, advancing a distal end of a drug delivery device to the suprachoroidal space, positioning a distal-most tip of the drug delivery device within the suprachoroidal space, and delivering a quantity of drug to the suprachoroidal space. Various embodiments of the method may include one or more of the following aspects: advancing the distal end of the drug delivery device to the suprachoroidal space may include penetrating the sclera; positioning the distal-most tip of the drug delivery device may include disposing the distal-most tip in the suprachoroidal space without contacting the choroid; positioning the distal-most tip of the drug delivery device may include disposing the distal-most tip in the suprachoroidal space without perforating the outermost surface of the choroid; positioning the distal-most tip of the drug may include disposing the distal-most tip in the suprachoroidal space without penetrating a thickness of the choroid; The amount of drug delivered to the suprachoroidal space can be about 50 μL to 500 μL; delivery of the amount of drug to the suprachoroidal space can be pressure-controlled; manipulating one of the sclera and choroidal layers can include rotating the drug delivery device; manipulating one of the sclera and choroidal layers can include stretching the scleral layer to increase the size of the suprachoroidal space; delivering the amount of drug solution to the suprachoroidal space can include delivering the amount from the distal-most tip of the drug solution delivery device; or delivering the amount of drug to the suprachoroidal space can include delivering the drug from a location proximal to the distal-most tip of the drug delivery device.

[0012] In another aspect, the present disclosure includes a device for enabling directed delivery of a medicament into a human organ of a patient, the device comprising: a container for the medicament fluidly connected to a needle, the needle comprising a needle shaft and a sharpened distal-most tip having a bevel, the needle connected to a distal end of the container; and an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharpened distal-most tip of the needle, the adapter including an outermost beveled surface configured to guide the trajectory of the sharpened distal-most tip to a predetermined depth and location within the human organ, the outermost beveled surface facing in the same direction as the bevel of the sharpened distal-most tip, the angle of the outermost beveled surface dictating the needle trajectory, and the length of the needle extending from the outermost beveled surface determining the depth and location of medicament delivery. Various embodiments of this device may include one or more of the following aspects: the sharp distal-most tip may be a portion of a needle extending from the distal end of the adapter; a needle hub / shaft connected to the proximal end of the needle, such as a needle; a hub disposed between the container and the needle; the needle is removably connected to the hub; the needle is a first needle and the device further comprises a second needle; the first and second needles are interchangeable; the needles are interchangeable; the angle is in the range of about 25 degrees to about 75 degrees; the angle is in the range of about 40 degrees to about 60 degrees; the angle is about 45 degrees; the adapter is connected to a portion of the needle shaft via a fastener or screw; the adapter is translatable relative to the axial path of the needle shaft; the adapter is attached to the needle shaft via an adhesive; The adapter can include a proximal end having a surface extending in a first plane perpendicular to the needle, an angled distal side, an intermediate surface extending between the proximal end and the angled distal side, the intermediate surface extending in a second plane perpendicular to the first plane, and a distal end, the distal end including a substantially flat surface extending in a third plane parallel to the first plane; at least a portion of the adapter includes a substantially cylindrical cross-section; the outermost beveled surface is angled with respect to the longitudinal axis of the adapter; a portion of the sharpened distal-most tip of the needle extends beyond the distal end of the adapter; the sharpened distal-most tip of the needle has a length in the range of about 600 μm to about 800 μm; the outermost beveled surface is a flat surface; and the outermost beveled surface is a convex surface configured to mate with the outer surface of the eye.

[0013] In another aspect, the disclosure includes a system for delivering a medication to a patient's ocular cavity, which may include a syringe having a nominal maximum fill volume of between about 0.5 mL and about 1.0 mL, a needle having a needle shaft and a sharpened distal-most tip with a bevel, and an adapter surrounding a portion of the needle shaft along its longitudinal axis, the adapter including an outermost beveled surface angled relative to the longitudinal axis of the adapter and configured to guide the trajectory of the sharpened distal-most tip to a predetermined depth and location in the eye, wherein the syringe, needle, and adapter are sterilized and contained within a blister pack. Various embodiments of the system may further include one or more of the following aspects: the adapter is configured to limit advancement of the distal-most tip into the suprachoroidal space of the eye; the sharp distal-most tip is a portion of the needle extending from an outermost bevel; the angle of the outermost bevel is in the range of about 25 degrees to about 75 degrees; the angle of the outermost bevel is in the range of about 40 degrees to about 60 degrees; the angle of the outermost bevel is about 45 degrees; and the sharp distal-most tip of the needle has a length in the range of about 600 μm to about 800 μm.

[0014] In another aspect, the disclosure includes a kit for treating a patient with an ocular disease, which may include a syringe having a nominal maximum fill volume of between about 0.5 mL and about 1.0 mL, a needle having a needle shaft and a sharp distal-most tip, an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharp distal-most tip, the adapter including an outermost beveled surface configured to guide the trajectory of the sharp distal-most tip to a predetermined depth and position in the eye, and an ophthalmic medication.

[0015] In another aspect, the present disclosure includes a kit for treating a patient with an ocular disease, which may include a syringe prefilled with an ophthalmic medication, the syringe having an amount of the ophthalmic medication in a range between about 0.5 mL and about 1.0 mL, a needle having a needle shaft, a passageway, and a sharp distal-most tip, and an adapter surrounding a portion of the needle shaft along a longitudinal axis of the needle shaft, excluding the sharp distal-most tip, the adapter including an outermost beveled surface configured to guide the trajectory of the sharp distal-most tip to a predetermined depth and position in the eye.

[0016] In another aspect, the present disclosure includes a method of delivering a medication to a patient's eye, which can include positioning a distal-most tip of a medication delivery device within the suprachoroidal space of the eye at a predetermined ocular depth and location, the medication delivery device can include a container for the medication fluidly connected to a needle, the needle including a needle shaft and a sharp distal-most tip having a bevel, the needle connected to a distal end of the container, and an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharp distal-most tip, the adapter including an outermost bevel configured to guide the trajectory of the sharp distal-most tip to the predetermined ocular depth and location, the method can further include delivering a quantity of the medication to the suprachoroidal space.

[0017] In another aspect, the present disclosure includes a method for delivering a drug to the suprachoroidal space of an eye using a drug device. The drug device may include a drug reservoir fluidly connected to a needle, the needle including a needle shaft and a sharp, distal-most tip having a beveled surface, and an adapter surrounding a portion of the needle shaft along its longitudinal axis, the adapter including an outermost beveled surface angled relative to the longitudinal axis. The method may include penetrating the sharp, distal-most tip into the sclera of the eye, inserting the needle through the sclera into the suprachoroidal space until the outermost beveled surface contacts the sclera, and delivering a quantity of drug to the suprachoroidal space when the outermost beveled surface contacts the sclera.

[0018] In another aspect, the present disclosure includes a method of delivering a drug to the suprachoroidal space of an eye, which may include treating one of the sclera or choroid layers of the eye to increase the size of the suprachoroidal space, advancing a distal end of a drug delivery device to the suprachoroidal space, positioning a distal-most tip of the drug delivery device within the suprachoroidal space, and delivering a quantity of drug to the suprachoroidal space. Various embodiments of this method may further include one or more of the following aspects: advancing the distal end of the drug delivery device to the suprachoroidal space may include penetrating the sclera; positioning the distal-most tip of the drug delivery device may include disposing the distal-most tip in the suprachoroidal space without contacting the choroid; positioning the distal-most tip of the drug delivery device may include disposing the distal-most tip in the suprachoroidal space without perforating the outermost surface of the choroid; positioning the distal-most tip of the drug may include disposing the distal-most tip in the suprachoroidal space without penetrating a thickness of the choroid; the amount of drug delivered to the suprachoroidal space is approximately 50 μL to 500 μL.

[0019] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate various examples and, together with the general description, serve to explain the principles of the disclosed examples and embodiments. Aspects of the present disclosure may be implemented in conjunction with the embodiments illustrated in the accompanying drawings. These drawings depict different aspects of the disclosure and, where appropriate, are similarly labeled with reference numerals that illustrate like structures, components, materials, and / or elements in the different figures. It is understood that various combinations of structures, components, and / or elements other than those specifically shown are contemplated and within the scope of the present disclosure.

[0020] Moreover, there are many embodiments described and illustrated herein. The present disclosure is not limited to any single aspect or embodiment, nor is it limited to any combination and / or permutation of such aspects and / or embodiments. Moreover, each aspect of the present disclosure and / or its embodiment may be used alone or in combination with one or more of the other aspects and / or embodiments of the present disclosure. For the sake of brevity, specific permutations and combinations are not separately described and / or illustrated herein. In particular, any embodiment or implementation described herein as "exemplary" should not be construed as, for example, preferred or advantageous over other embodiments or implementations, but rather as reflecting or indicating that one or more embodiments are one or more "exemplary" embodiments. [Brief explanation of the drawings]

[0021] [Figure 1A-1B] 1 is a cross-sectional view of an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 2] 1 is a cross-sectional view of an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 3A] 1 is a cross-sectional view of an exemplary instrument according to an embodiment of the present disclosure. [Figure 3B] 1 is a cross-sectional view of an exemplary instrument according to an embodiment of the present disclosure. [Figure 4A-4B] 1 is a cross-sectional view of an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 5A-5B] 1 is a cross-sectional view of an exemplary instrument according to an embodiment of the present disclosure. [Figures 6A-6B] 6A is a cross-sectional view of an exemplary device according to an embodiment of the present disclosure, and FIG. 6B is a top view of the device of FIG. 6A according to an embodiment of the present disclosure. [Figures 7A-7B] 1 depicts an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 7C] 1 depicts an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 8A-8B]10 depicts another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 8C] 10 depicts another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 8D-8F] 10 depicts another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 9] 10 depicts another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure. [Figure 10] 10A-10C depict further exemplary instruments treating ocular tissue, according to embodiments of the present disclosure; [Figures 11A-11B] FIG. 10 depicts another exemplary instrument according to an embodiment of the present disclosure. [Figures 12A-12B] 1 is a cross-sectional view of an exemplary tubular shaft of an exemplary instrument, in accordance with an embodiment of the present disclosure. [Figure 13] FIG. 10 is a side view of another exemplary instrument according to an embodiment of the present disclosure. [Figure 14] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 15] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 16] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 17] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 18] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 19] 10 is a cross-sectional view of yet another exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figure 20] 1 is a top view of an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; [Figures 21A-21B] FIG. 10 is a perspective view of another exemplary instrument according to an embodiment of the present disclosure. [Figures 22A-22B]10 is a perspective view of a further exemplary instrument according to an embodiment of the present disclosure; [Figures 23A-23C] FIG. 23A is a cross-sectional view of yet another exemplary instrument according to an embodiment of the present disclosure, FIG. 23B is a cross-sectional view showing the exemplary instrument of FIGS. 23A and 23C treating ocular tissue according to an embodiment of the present disclosure, and FIG. 23C is a cross-sectional view of yet another exemplary instrument according to an embodiment of the present disclosure. [Figure 24] 1 is a partial perspective view of an exemplary instrument according to an embodiment of the present disclosure. [Figure 25] FIG. 10 is a partial perspective view of another exemplary instrument according to an embodiment of the present disclosure. [Figures 26A-26B] 1 is a partial perspective view of an exemplary instrument according to an embodiment of the present disclosure. [Figures 27A-27B] 10A-10C are cross-sectional views illustrating further embodiments of an apparatus being used to deliver a drug to ocular tissue, according to embodiments of the present disclosure. [Figure 28] 1 is a perspective view of an exemplary instrument according to an embodiment of the present disclosure. [Figure 29] 1 is a cross-sectional view of an exemplary instrument according to an embodiment of the present disclosure. [Figure 30] 1 depicts an exemplary instrument treating ocular tissue in accordance with an embodiment of the present disclosure; DETAILED DESCRIPTION OF THE INVENTION

[0022] As used herein, the terms "comprise," "comprising," "include," "including," or any other variant thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements does not include only those elements, but may include other elements not expressly listed or inherent in such process, method, article, or apparatus. The term "exemplary" is used in the sense of "example," not "ideal." Additionally, the terms "first," "second," etc., are used herein not to denote any order, quantity, or importance, but rather to distinguish one element or structure from another. Furthermore, the terms "a" and "an" as used herein do not denote a limitation of quantity, but rather, to denote the presence of one or more of the referenced items.

[0023] In particular, for simplicity and clarity of illustration, certain aspects of the figures depict the general structure and / or manner of construction of various embodiments. Descriptions and details of well-known features and techniques may be omitted to avoid unnecessarily obscuring other features. Elements in the figures are not necessarily drawn to scale, and the dimensions of some features may be exaggerated relative to other elements to improve understanding of the illustrative embodiments. For example, those skilled in the art will understand that side views are not drawn to scale and should not be viewed as depicting proportional relationships between separate components. The side views are provided to help illustrate the various components of the depicted assembly and to show their relative placement to one another.

[0024] Reference will now be made in detail to examples of the present disclosure, which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. The term "distal" refers to the portion of the device that is furthest from the user when introducing the device into a subject. In contrast, the term "proximal" refers to the portion of the device that is closest to the user when entering the subject. In the following description, relative terms such as "about," "substantially," and "approximately" are used to indicate a ±10% variation of the stated numerical value.

[0025] Aspects of the present disclosure relate, inter alia, to devices and methods for delivering drugs to ocular tissues. Each of the aspects disclosed herein may include one or more of the features described in connection with any of the other disclosed aspects. It should be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any claimed invention.

[0026] The suprachoroidal space (SCS) is the potential space between the sclera and the choroid that circumscribes the posterior segment of the eye. The SCS is a useful site for drug delivery because it targets the highly bioavailable choroid, retinal pigment epithelium, and retina while maintaining low levels elsewhere in the eye. Under physiological conditions, the SCS is naturally compressed, primarily due to intraocular pressure (IOP). The SCS maintains IOP through the uveoscleral pathway, which is an alternative drainage route for aqueous humor and the natural flow path from the anterior to the posterior part of the eye. Due to its role in maintaining IOP, the SCS has the potential to expand and contract in response to the presence of fluid. The SCS can expand to accommodate different volumes, e.g., up to approximately 3.0 mm, depending on the injection volume. Injecting large volumes of medication can have adverse effects, such as localized serous retinal elevation, choroidal hemorrhage away from the needle entrance, and IOP elevation, which can cause choroidal edema and potential choroidal detachment, reflux from the needle entrance, and backflow of fluid, which can cause subconjunctival hemorrhage. Additionally, large volumes of fluid cannot be injected into the eye until the needle of the injection device has completely penetrated the sclera.

[0027] For example, to expand the SCS by mechanically separating the sclera and choroid and breaking the fibers holding them together, an instrument can be inserted through the sclera and positioned to allow an optimal amount of fluid (e.g., a drug) to be injected into the SCS at the correct depth between the scleral and choroidal layers. Any drug inserted into the SCS may enable direct drug delivery to the posterior section of the eye, for example, to specifically target the retina and / or macula. The instrument and method for insertion and injection into the eye may only allow for expansion to a specific depth of the ocular layers. For example, the scleral layer may range from about 500 μm to about 1100 μm, the SCS may have a thickness of about 35 μm, and the choroidal layer may range from about 50 μm to about 300 μm. The insertion depth of the instrument for drug delivery to the ocular layers may range from about 1 mm to about 10 mm. However, such depths of insertion may penetrate and / or affect additional layers of ocular tissue, such as the choroid, retinal pigment epithelium (RPE), and retina. Penetration of such layers should be minimized as much as possible so that the desired drug can be delivered to the target area of ​​the eye through a minimally invasive procedure. For example, the injection procedure may be performed as an outpatient procedure. The devices and methods described in the present disclosure address the above-mentioned shortcomings and can increase the ability of the SCS to hold and distribute optimal volumes of drug, e.g., 50 μL to 500 μL.

[0028] The exemplary embodiments described herein may be used in the treatment of various conditions, including ocular conditions. For example, embodiments of the present disclosure may be used in the treatment of refractive errors, macular degeneration, cataracts, retinopathy, retinal detachment, glaucoma, amblyopia, strabismus, any other ocular disease, or any other condition suitable for treatment via ocular tissue.

[0029] The above description and examples are illustrative, not limiting. Numerous modifications and / or variations may be made by those skilled in the art without departing from the general scope of the invention. For example, as noted, aspects of the above-described embodiments may be used in any suitable combination with each other. In addition, portions of the above-described embodiments may be removed without departing from the scope of the invention. In addition, modifications may be made to adapt a particular situation or aspect to the teachings of the various embodiments without departing from the scope of those teachings. Many other embodiments will also be apparent to those skilled in the art upon reviewing the above description.

[0030] 1A and 1B, different tissues and layers of the eye are depicted, such as the sclera 2, the SCS 4, and the choroid 6. FIGS. 1A-4B show various views of an instrument 10 for manipulating layers of ocular tissue to enable delivery of an agent to the suprachoroidal space of the eye. The instrument 10 may include a needle 12 and a tubular shaft 14. The needle 12 may have a passageway 16 and a distal-most tip 18. The tubular shaft 14 may be disposed within the needle 12 and may be longitudinally translatable relative to the needle 12, such that the instrument 10 can be inserted into a patient's eye to create separation between different tissues of the eye (e.g., by moving the tissues away from each other and breaking fibers and / or bonds within the different tissues) and / or remove tissue within the eye, while at least a portion of the instrument 10 can remain outside the eye where it can be held by a user. A medication, i.e., a drug, may be contained within the needle 12 or the tubular shaft 14, or both the needle 12 and the tubular shaft 14. In instances where the device 10 is inserted into a subject's eye and the tubular shaft 14 may be positioned to create and / or augment the SCS4 (FIG. 1B), the medication may flow more readily from the device insertion site 24 and spread over an area of ​​tissue and / or an expanded area 26 of the SCS4, helping to prevent adverse reactions associated with drug injection. Spreading the medication over the tissue area may also prevent backflow of the drug from the device insertion site 24 and improve bioavailability in the posterior section of the eye.

[0031] The distal-most tip 18 may be a sharp tip or needle configured to penetrate a tissue layer of the eye, such as the sclera 2. The distal end 20 may have a substantially atraumatic or blunt tip 22 that resists penetration into the choroid 6 (FIG. 1A). When the device 10 is inserted into the subject's eye, the tubular shaft 14 may be pushed longitudinally through the passageway 16 to separate the sclera 2 and choroid 6 (e.g., by pushing against and / or otherwise deforming the sclera 2 and / or choroid 6), thereby forming an extension portion 26 (FIG. 1B) of the SCS 4. The device 10 may include a plurality of openings 150 that allow a drug to flow from the device 10 into the SCS 4. For example, the openings 150 may be circular, slotted, or a combination thereof (FIGS. 11A and 11B). The openings 150 may be arranged in the needle 12 or the tubular shaft 14, or in both the needle 12 and the tubular shaft 14, in any suitable configuration that allows the drug to flow from the device 10. For example, the openings 150 may be disposed radially along the length and / or around the needle 12 (e.g., in the sidewall of the needle 12) or the tubular shaft 14, or both the needle 12 and the tubular shaft 14. In some examples, the device 10 may include 2 to 30 openings, or more than 30 openings. Referring to FIGS. 11A and 11B, the device 10 can be inserted into the patient's eye parallel to the plane of the SCS 4 so that the drug flows out of the device 10 across a region of the SCS 4, helping to prevent adverse reactions associated with the drug entering the SCS 4.

[0032] The tubular shaft 14 may be solid, i.e., not include any openings, so that the drug can flow out of the needle 12 and around the tubular shaft 14. In such an example, the tubular shaft 14 may include a cross-sectional dimension that is smaller than the cross-sectional dimension of the passageway 16, thereby allowing the drug to flow around the tubular shaft 14. The tubular shaft 14 may have various configurations to allow drug flow around the tubular shaft 14 and from the insertion site 24 (FIG. 1B). FIGS. 12A and 12B show exemplary geometries of the tubular shaft 14. For example, the tubular shaft 14 may have a star shape (FIG. 12A) with multiple arms 160 extending from and connected to a radial center 162, allowing the tubular shaft 14 to gently separate the sclera 2 and choroid 6, containing channels 164. The channels 164 may allow the drug to exit the needle 12, flow around the tubular shaft 14, and away from the injection site 24. Drug flow 166 around the arms 160 of the tubular shaft 14 is shown in FIG. 12A . In another example, the tubular shaft 14 may include at least one pair of channels 164 ( FIG. 12B ) so that the needle 12 can be inserted in a specific orientation, with the channels 164 oriented within the plane of the SCS 4. When a drug is injected through the needle 12, the drug can flow through the channels 164 and be pushed outward / away from the tubular shaft 14. This configuration of the tubular shaft 14 may be beneficial during the manufacturing process of the device 10, as the channels 164 may be formed on the exterior surface of the tubular shaft 14, as opposed to the interior region of the tubular shaft 14. Drug flow 166 through the channels 164 of the tubular shaft 14 is shown in FIG. 12B . This configuration of the tubular shaft 14 may be further useful for injecting substances of different viscosities into the SCS 4. For example, a low-viscosity fluid may be injected through channel 164, which advantageously spreads the low-viscosity fluid throughout SCS 4. Tubular shaft 14 may then be removed from needle 12, effectively increasing the size of the flow path. In this case, a viscous fluid, such as a gel, may be injected through needle 12. Thus, tubular shaft 14 can also facilitate the diffusion of the low-viscosity fluid without permanently obstructing the flow path of the high-viscosity fluid.

[0033] In yet another example, different substances can be caused to flow through each of the channels 164 of the tubular shaft 14. For example, one drug can be caused to flow through one of the channels 164, and another substance can be caused to flow through another of the channels 164. These substances can be caused to flow through the channels 164 and injected sequentially or in parallel into the patient's eye. Such a configuration can be useful, for example, in situations where the drug is in pellet form and requires hydration for release from the pellet into the tissue. The drug pellet can be injected through one of the channels 164, and a hydrating fluid can be caused to flow through another of the channels 164. Upon exiting the flow path 164, the pellet and hydrating fluid can mix, allowing the drug to be released from the pellet into the tissue. As another example, substances of different viscosities can be injected into the eye through separate channels 164. As yet another example, substances that polymerize when mixed can be injected into the eye through separate channels 164. By injecting these substances through separate channels 164, the substances can be kept separate and polymerization can be prevented until the substances enter the target space in the eye.

[0034] In some embodiments, the tubular shaft 14 may be formed, in whole or in part, of an absorbent material, such as, for example, a sponge. In such a configuration, the tubular shaft 14 may be used to absorb fluid that accumulates within the SCS 4 or elsewhere in the patient's eye. Fluid accumulation may occur due to insertion of the instrument 10 into the patient's eye, excessive bleeding, bleeding, or general buildup. Upon insertion of the instrument 10 into the SCS 4, the tubular shaft 14 may be selectively translated toward the SCS 4 relative to the needle 12 to absorb fluid proximate its distal-most tip 18 within the SCS 4. In embodiments in which the tubular shaft 14 is formed, in part, of an absorbent material, the blunt tip 22 (shown in FIGS. 1A and 1B ) of the tubular shaft 14 may be formed, in whole or in part, of an absorbent material. The blunt tip 22 itself may similarly be formed, in whole or in part, of an absorbent material.

[0035] In some embodiments, the tubular shaft 14 may alternatively be formed of a drug or agent. For example, the tubular shaft 14 may be formed of a solidified drug, such as a lyophilized drug. Once the instrument 10 is inserted into the SCS 4, the tubular shaft 14 may be translated toward the SCS 4 relative to the needle 12. Once the tubular shaft 14 is extended into the SCS 4, the tubular shaft 14, or a portion thereof, may break or otherwise separate from the instrument 10, thereby allowing application of the drug into the SCS 4.

[0036] The distal end 20 may include an expandable member 28 ( FIG. 2 ). The expandable member 28 may be any suitable component, such as a stent or a balloon. The expandable member 28 may be expandable vertically to separate the sclera 2 and the choroid 6, to increase the SCS 4 and / or its horizontal thickness, or to expand across a region of the SCS 4. For example, the expandable member 28 may expand the sclera 2 upward, i.e., away from the choroid 6, to increase the SCS 4. In other words, the expandable member 28 may expand to allow an increased amount of drug to flow more easily from the device 10 into the SCS 4. Referring to FIG. 3A , the tubular shaft 14 may include an expandable portion 30. The expandable portion 30 may be expandable vertically and / or horizontally to expand across a region of the SCS 4. For example, the expandable portion 30 can include a pair of curved arms located proximal to the distal tip 20 (FIG. 3A) so that the drug can flow from the injection site 24 out of the expandable portion 30 and into the expansion region 26 of the SCS 4. In some examples, the drug can flow out of multiple openings 150 in the tubular shaft 14 and / or the expandable portion 30. In other examples, the expandable portion 30 can include multiple threads 32 (FIG. 3B). The threads 32 can capture the sclera 2 as the expandable portion 30 expands vertically and / or horizontally.

[0037] The components of instrument 10 may be made of any suitable metal, polymer, and / or combination of metal and / or polymer. Exemplary metallic materials may include stainless steel, nitinol, titanium, and / or alloys of these metals. Exemplary polymeric materials may include polyetheretherketone (PEEK), polyimide, and polyethersulfone (PES). In some examples, tubular shaft 14 may be made of a rigid, semi-rigid, or flexible material, which may be expandable and / or capable of the various configurations described herein. The material of instrument 10 may be any biocompatible material that can be sterilized.

[0038] 4A and 4B, the instrument 10 may have a curved or fishhook shape. The curvature of the instrument 10 may allow the user to insert the instrument 10 to a desired depth between the sclera 2 and the choroid 6, rotating and / or lifting the instrument 10 to separate a portion of the sclera 2 from the SCS 4, creating an expanded portion 26. As shown in FIG. 4B, the SCS 4 may expand outward, i.e., away from the choroid 6, rather than inward, which may help avoid adverse effects when injecting drugs into ocular tissue. The tubular shaft 14 may be advanced to further separate the sclera 2 and the choroid 6 (FIG. 4B), which may allow the injected drug to spread more evenly between the sclera 2 and the choroid 6. The bevel or opening of the needle 12 may be positioned in any direction relative to the curvature of the instrument 10, including toward the center of the curvature, away from the center of the curvature, or any direction in between. Additionally, instrument 10 can include a magnetic element or can be formed in whole or in part from a magnetic material. A magnet external to the patient's eye can be used to act on the magnetic element or material to guide instrument 10 as it is inserted into the SCS 4 and while it is positioned between the sclera 2 and the choroid 6. For example, the external magnet can be positioned outside the patient's eye near the outer surface of the sclera 2. The external magnet can exert a magnetic force on needle 12, thereby moving needle 12 toward the sclera 2 and maintaining the portion of needle 12 within the SCS 4 in an orientation parallel or nearly parallel to the sclera 2 so as not to inadvertently penetrate the choroid 6.

[0039] Various configurations of, and components of, instrument 10 are described herein. Figures 5A and 5B depict an alternative embodiment in which instrument 50 may include a needle 52 and a shaft 54 ​​(e.g., a tubular shaft). Needle 52 may include a passageway 56 and a distal end 57, and tubular shaft 54 ​​may include a distal-most tip 58. Distal-most tip 58 may be a pointed or sharp tip configured to penetrate tissue layers of the eye. Distal end 57 may have a substantially atraumatic or blunt tip 59. As shown in Figures 5A and 5B, distal-most tip 58 may include multiple angled / curved surfaces to allow tubular shaft 54 ​​to be pulled back in passageway 56 once needle 52 is inserted into the sclera. While the tubular shaft 54 ​​is being pulled through the passageway 56, the angled / curved surface of the distal-most tip 58 forces a portion of the distal end 57 to spread apart ( FIG. 5B ), which may separate the scleral and choroidal layers and allow the drug to flow more easily from the injection site. The tubular shaft 54 ​​can also be pushed back into its original orientation in 56, as shown in FIG. 5A . The drug can be delivered through one or more openings in the distal tip 58, as depicted by the arrows in FIG. 5B . The device 50 may include a lock / unlock mechanism to prevent the tubular shaft 54 ​​from being pushed back into the passageway 56 while the device 50 is inserted into the sclera. In other examples, a portion of the needle 52 may be shaped or curved to resemble the shape or curvature of the eye.

[0040] 6A and 6B depict an alternative embodiment in which an instrument 60 may include a needle 61 and a tubular shaft 62. The needle 61 may include a passageway 63 and a distal-most tip 64, and the tubular shaft 62 may include a distal end 65. The distal-most tip 64 may be a sharp tip or a needle configured to penetrate the tissue layers of the eye. The distal end 65 may have a substantially atraumatic or blunt tip 66. As shown in FIG. 6A, the tubular shaft 62 may be configured such that when the instrument 60 is inserted into the sclera of the eye, a wedge 67 of the instrument 60 engages the tubular shaft 62, forcing a portion of the tubular shaft 62 to spread apart in the plane of the SCS (FIG. 6B), separating the scleral and choroidal layers and allowing the drug to more easily flow and spread from the injection site. For example, the tubular shaft 62 may include a split 68 that allows a portion of the tubular shaft to spread apart, as shown in FIG. 6B. 6B is a top view of instrument 60 showing expanded distal end 65 of tubular shaft 62. Wedge 67 may be any suitable shape configured to engage and force apart portions of tubular shaft 62. In some embodiments, wedge 67 may be omitted and distal end 65 may be configured to self-expand to form a division 68 as soon as distal end 65 is advanced out of passageway 63.

[0041] 7A-7C show exemplary components of the distal end of a tubular shaft 76 extending from a needle 70. The needle 70 may include at least one opening 74. The distal end of the tubular shaft 76 may include an anchor 72. The anchor 72 may have a concave curvature. A user can insert the needle 70 into the sclera 2 and choroid 6 (FIG. 7A) and then retract the needle 70 toward the user and away from the choroid 6 of the eye. As the needle 70 retracts, the anchor 72 activates and engages the inner surface of the sclera 2 (FIG. 7B), thereby anchoring the needle 70 at a desired depth within the SCS 4. The anchor 72 can anchor when it hits the sclera 2 due to the difference in mechanical properties between the sclera 2 and other soft layers of ocular tissue. The anchor 72 can also pull the sclera 2 away from the choroid 6, thereby increasing the portion of the SCS 4. In some embodiments, the anchor 72 may be formed in whole or in part from a magnetic material so that a magnet external to the patient's eye can be used to pull the sclera 2 away from the choroid 6. This embodiment may require penetration of the choroid 6, but may allow the user to easily reach the proper insertion depth without precise device geometry. In another embodiment, as shown in FIG. 7C , the anchor 72 can be configured to prevent penetration of the choroid 6. For example, the anchor 72 may have a flat or other atraumatic shape or configuration to abut against the choroid 6 without penetrating the tissue layer. The anchor 72 can be manually pushed out of the needle 70, or the anchor 72 can automatically extend from the needle 70 when the penetration force decreases. In some examples, the anchor 72 may be formed from a flexible or semi-flexible material so that a portion of the anchor 72 can bend. For example, once the injection is complete, a portion of the anchor 72 may bend toward the choroid 6 as the needle 70 is retracted / removed from the tissue layer.

[0042] In some embodiments, the anchor 72 can be configured to engage the inner surface of the choroid 6. In such embodiments, the user can insert the needle 70 through the sclera 2 and choroid 6 ( FIG. 7A ) and then retract the needle 70 toward the user. As the needle 70 retracts, the anchor 72 is actuated and engages the inner surface of the choroid 6, thereby separating the choroid 6 from the underlying retina. Because the choroid 6 is formed of soft tissue, the anchor 72 can be configured to separate the choroid 6 from the retina without tearing or rupturing the choroid 6. Such a configuration can be particularly useful for administering treatments, such as gene therapy, in the subretinal space to address various abnormalities, such as retinal detachment.

[0043] 8A-8F illustrate exemplary embodiments of an instrument 10 and a method for delivering a drug to the SCS 4 of the eye. The instrument 10 may include all or some of the features described above. As shown in FIG. 8A, the instrument 10 may have a curved or fishhook shape. The curvature of the instrument 10 may allow a user to insert the instrument 10 to a desired depth between the sclera 2 and the choroid 6 so that the user can rotate and / or lift the instrument 10 to pull a portion of the sclera 2 away from the SCS 4, thereby creating an extension 26. As shown in FIG. 8B, the SCS 4 may be extended outward rather than inward, i.e., away from the choroid 6, which may help avoid adverse effects when injecting drugs into ocular tissue. In some instances, a needle 80 may be inserted into the extension 26. Using the instrument 10 in combination with the needle 80 requires less precision from the user because the distance between the sclera 2 and the choroid 6, i.e., the extension 26, is increased. However, use of device 10 in combination with needle 80 may need to be precisely controlled as this method utilizes two insertion sites, one for device 10 and a second for needle 80.

[0044] FIG. 8C illustrates an alternative second device, stabilizing leg 82, for use in combination with device 10. Stabilizing leg 82 can be attached to device 10 such that a user can control how deeply device 10 is inserted through sclera 2 and SCS 4 by using both components. Compared to the system and method shown in FIG. 8B, use of stabilizing leg 82 utilizes a single insertion site, which may reduce the risk of patient infection, discomfort, and / or trauma. Stabilizing leg 82 also provides an additional means of user control.

[0045] 8D and 8E show an alternative embodiment of the instrument 10 including a bend 84 located proximal to the distal-most tip 18. The bend 84 can control how deeply the instrument 10 can be inserted through the sclera 2 and SCS 4. Once the instrument 10 is inserted, the user can rotate the instrument 10 to inject a quantity of drug into the expansion portion 26 while simultaneously pulling a portion of the sclera 2 away from the choroid 6. FIG. 8F shows an alternative embodiment of the instrument 10 configured in a substantially U-shape. Because the instrument 10 is U-shaped, the user can control how deeply the instrument 10 can be inserted through the sclera 2, SCS 4, and choroid 6. Once the instrument 10 is inserted, the user can push / rotate the instrument 10 so that the distal-most tip 18 points upward toward the sclera 2, preventing a second insertion into the sclera 2. The difference in mechanical properties between the sclera and other soft layers can provide the user with tactile feedback indicating that the user may need to stop the advancement of the needle before it re-penetrates the scleral layer from the inside. The U-shape can allow the user to find the proper injection depth without requiring a very precise device geometry, although utilizing a U-shaped instrument will penetrate the choroid 6 in some embodiments.

[0046] In some examples, the needle 12 may include two or more distal-most tips 18. Referring to FIG. 9 , one or more distal-most tips 18 of the needle 12 may form a Y-shape, which may allow the needle 12 to have two infusion sets entering the sclera 2. The one or more distal-most tips 18 may span an area of ​​the sclera 2, allowing the drug to spread to a wider area of ​​the SCS 4. The openings of the one or more distal-most tips 18 may be oriented in various directions, including outward from the main shaft of the needle 12, inward toward the main shaft, or various directions in between. The openings can be oriented to maximize the flow of the drug from the needle 12 and the surface area over which the drug flows. Additionally, while the one or more distal-most tips 18 are shown in FIG. 9 as extending straight from the needle 12, they may also generally form a semicircular shape that resembles the shape of the outer surface of a patient's eye. Such a configuration may allow one or more distal-most tips 18 to be inserted near the limbus of the eye and for the drug to flow toward the back of the eye when injected through needle 12.

[0047] Using the device or system disclosed herein, the differences in mechanical and / or chemical properties between the vitreous, choroid, and sclera may allow a user to feel tactile feedback when the device, system, or component thereof reaches the inner surface of the sclera. In other words, based on the properties of the tissue layers, a user may know once the device, system, or component thereof has been inserted to the correct depth. For example, the sclera may be approximately 10 times stiffer than the choroid. While standard needles are inserted into the eye at an angle to follow the curvature of the eye, and the user may use tactile feedback as described above, such methods may increase the risk of ocular trauma. Referring to FIG. 13, the needle 12 may include a geometric feature 170 configured to provide tactile feedback to the user. The geometric feature 170 may be a notch or a rib and may be positioned at set intervals, for example, every 100 μm (represented by A in FIG. 13). In addition to providing tactile feedback to the user, the geometric feature 170 may also provide audible feedback to the user. For example, geometric feature 170 may produce a clicking sound upon insertion into one or more depths into the eye or into one or more cavities of the eye. In some embodiments, geometric feature 170 may include one or more sensors configured to detect the depth of insertion of needle 12. Based on signals generated by the one or more sensors indicating insertion into one or more depths into the eye, a sound may be generated to alert the user to the depth of insertion. The sound can be generated by any sound-generating device, such as a small electronic speaker, on needle 12, on the needle hub, on the syringe housing, or located near but separate from needle 12. Thus, geometric feature 170 may enable a user to use needle 12 for injection into any of several cavities of the eye, such as the suprachoroidal space, the vitreous humor, or other cavities.

[0048] Differences in the properties of tissue layers can also help control the flow of drug. For example, needle 12 can have multiple openings 150, as shown in FIGS. 11A and 11B. In some examples, openings 150 can be configured around and / or along the length of needle 12. When needle 12 is inserted into a tissue layer, the different chemical and / or mechanical properties of the tissue layers can block openings 150, preventing a quantity of drug from flowing out of needle 12 and into areas of the tissue layer other than the SCS.

[0049] Referring to FIG. 10 , an external portion 100 can be utilized with a needle 12. The external portion 100 can have a flat surface with protrusions for deforming one or both of the sclera 2 and choroid 4. For example, the protrusions can be rounded. The external portion 100 can be applied to the exterior surface of the eye to cause deformation in one or both of the sclera 2 and choroid 4. As shown in FIG. 10 , once the external portion 100 is applied to the exterior surface of the eye, the needle 12 can be inserted at an appropriate angle and / or distance from the deformed region of the sclera 2 and / or choroid 4 so that the needle 12 can be wedged between the sclera 2 and choroid 4. While use of the external portion 100 can assist in inserting the needle 12 at the proper depth, the external portion 100 does not necessarily increase the area of ​​the SCS 4 for drug delivery.

[0050] 14-17 illustrate exemplary embodiments of the present disclosure utilizing a chamber 110 in conjunction with a needle 12. The chamber 110 can be configured to pull, grasp, or pinch a portion of the sclera 2. For example, the chamber 110 can have a circular shape and / or components that can grasp a portion of the sclera 2 and pull that portion of the sclera 2 into the chamber 110. Referring to FIG. 14, the chamber 110 can include a portion 110a and a shield 110b extending from a distal surface of the portion 110a. The portion 110a can be a stationary table, a tray, or a front cradle. The needle 12 can be connected to the chamber 110 by any suitable means, such as a needle hub 112. The chamber 110 can be automatically or manually actuated by a user such that the chamber 110 pinches and pulls a portion of the sclera 2 into the chamber 110, i.e., away from the choroid 6 (as shown in FIG. 15). In some examples, the chamber 110 can be configured to apply suction to the sclera 2. For example, the chamber 110 can include a vacuum, such as a dynamic or static vacuum. With reference to FIG. 15 , the chamber 110 can include a vacuum to apply suction to a portion of the sclera 2. Once the portion of the sclera 2 is pulled into the chamber 110 and away from the choroid 6, the needle 12 can be inserted into that portion of the sclera 2. FIG. 16 shows another embodiment in which the chamber 110 can be applied to a portion of the sclera 2. The chamber 110 can include a vacuum that pulls the portion of the sclera 2 upward into the chamber 110. The needle 12 can be inserted at the base of the chamber 110, for example, at a location distal to the shield 110b.

[0051] In another embodiment, the chamber 110 can include a stop component 114 configured to limit proximal advancement of the sclera 2 into the chamber 110 ( FIG. 17 ). For example, the stop component 114 can surround a portion of the needle 12. The stop component 114 can include multiple extensions 116 extending from the sidewall of the chamber 110 toward the center of the chamber 110. The stop component 114 can also include multiple openings 117 configured to allow application of suction to the sclera 2, for example, from a vacuum. The stop component 114 can be further configured to allow a user to adjust the angle of injection. For example, rotating the stop component 114 and / or the chamber 110 about the longitudinal axis of the needle 12 can adjust the angle of penetration of the needle 12 into the sclera 2. In some embodiments, by rotating the stop component 114 and / or the chamber 110, a user can adjust the angle of penetration from about 90° to about 45° (as shown in FIG. 17 ) relative to the surface of the sclera 2. The stop component 114 can, for example, deflect the needle 12 if the needle 12 has a flexible structure or is formed of a flexible material, thereby adjusting the angle of penetration.

[0052] As described above, the shield 110b of the chamber 110 may include a circular cross-sectional structure. Referring to FIG. 20 , instead of applying suction to the entire circular cross-section of the sclera 142 surrounded by the shield 110b, suction can be applied in a horseshoe or semicircular shape 140. In such a case, the shield 110b of the chamber 110 may include a semicircular cross-sectional structure. Applying suction to the horseshoe shape 140 can pull a portion of the sclera 142 upward into section 144. Next, the user can insert the needle 12 horizontally (into the sclera 142 and tangent to the natural ocular surface) between the center and two sides of the horseshoe shape 140. Further insertion of the needle 12 can wedge the needle 12 between the sclera layer and the choroid layer. The systems and methods of use disclosed herein, for example, in Figures 14-17 and 20, can be minimally invasive to the patient while creating an additional cavity within the SCS 4 without disturbing the choroid 6. Precision of needle insertion is less critical due to the increased area of ​​the SCS 4 caused by the use of vacuum.

[0053] The systems and methods described herein, which may include a chamber 110, may be utilized to prevent a drug from being withdrawn from a needle or device. For example, referring to FIG. 15 , a needle 12 can be partially inserted into a portion of the eye. The chamber 110 can suction a portion of the sclera 2, pulling that portion of the sclera 2 up and covering the distal-most tip 18. In another example, a delivery system and / or device according to the present disclosure may have a greater frictional force than the chamber 110, such that the chamber 110 can pull up a portion of the sclera 2 while allowing the drug to flow out of the needle 12 and into the SCS 4. In another example, a valve, such as a shut-off valve, may be present in the needle 12, needle hub 112, or any component of a device or apparatus according to the present disclosure. The valve can be used to shut off or unblock the flow of drug from the needle 12. For example, after the chamber 110 is applied to the sclera 2 and a portion of the sclera 2 is aspirated and drawn up into the chamber 110, the needle 12 is inserted and the valve is utilized to unblock the flow of drug from the needle 12 to the SCS 4 and then blocked to stop the flow of drug from the needle 12.

[0054] In some embodiments, the chamber 110 can rest against the exterior surface of the eye to act as a guide for the user (FIG. 19). The user can rest the shield 110b of the chamber 110 against the exterior surface of the eye and then advance the needle 12 from the needle hub 112 into the sclera 2. As shown in FIG. 19, the chamber 110 can include a dial or crank 220 for advancing the needle 12. The devices and methods disclosed herein, for example, in FIG. 19, allow for precise control of needle insertion depth.

[0055] In another example shown in FIG. 18 , a needle hub 112 can house a portion of the needle 12, and the needle hub 112 can be attached to a holder 210. The holder 210 can be attached to a table, tray, or front cradle, which can be secured to a stable external surface to assist the user. The holder 210 can include a dial or crank 220 for advancing the needle 12. The needle hub 112 can include a feedback mechanism, such as a force sensor, to stop the needle 12 from extending from the holder 210 upon detecting a decrease in penetration resistance. As explained above, penetration resistance can refer to the mechanical and / or chemical properties of ocular tissue layers. The dial 220 can be used to insert the needle 12 into the eye in a controlled manner until the feedback mechanism notifies the user to stop due to a decrease in force and / or penetration resistance. The feedback mechanism can be a feedback loop so that the insertion of the needle 12 can automatically stop.

[0056] 21A and 21B, the systems and methods described herein may include a microneedle hub 180. The microneedle hub 180 may be substantially rectangular and include multiple curved surfaces. The microneedle hub 180 may include multiple microneedles 182. As shown in FIGS. 21A and 21B, the microneedles 182 may vary in length and thickness. In another example, the microneedles 182 may vary in angle, i.e., the microneedles 182 may vary in angle relative to the surface of the microneedle hub 180. In some embodiments, the microneedles 182 may be angled by approximately 45° relative to the microneedle hub 180. In some embodiments, each of the microneedles 182 may be angled in the same direction. In some embodiments, one or more of the microneedles 182 may be angled in different directions. The microneedle hub 180 can provide gradual firing of different microneedle settings, similar to a tattoo needle. This gradual firing can spread the drug over a wide range of ocular tissue. The variable lengths of the microneedles 182 (FIG. 21B) can provide user flexibility when addressing the various thicknesses of ocular tissue layers (e.g., the sclera). In some embodiments, the microneedles 182 can include openings (not shown) at the distal end of each microneedle 182. The openings of the microneedles 182 can be oriented in multiple directions to allow drug to flow in multiple directions relative to the microneedle hub 180. In some embodiments, the microneedles 182 can be formed with a lyophilized drug so that the microneedles 182 dissolve upon insertion into a patient, thereby releasing the drug. The microneedle hub 180 can be utilized alone or in combination with any of the devices, systems, and methods disclosed herein.

[0057] In some embodiments, the microneedle hub 180 and / or the microneedles 182 may include a spring-loaded mechanism. When the microneedles 182 are pressed against the eye, the spring-loaded mechanism may cause the microneedles 182 to angularly deflect relative to the microneedle hub 180. In some embodiments, the microneedles 182 may be arranged in a circular or semicircular formation and may deflect outward relative to this formation. Deflecting the microneedles 182 may allow the microneedles 182 to penetrate the eye at a sufficiently shallow angle to separate the sclera 2 and choroid 6 layers to allow for better and increased drug flow and further maximize the area over which the drug is dispersed.

[0058] Another embodiment shown in FIGS. 22A and 22B includes a needle tube 190 having a needle tip 192. The needle tube 190 may have a cylindrical shape, and the needle tip 192 may be a serrated needle tip. The needle tip 192 vibrates on the outer surface of the eye, and this vibration may allow the needle tip 192 to cut open the sclera 2 without penetrating the choroid 6. In some examples, the needle tube 190 having the needle tip 192 may be surrounded by a chamber 194, as described above, which may contain a vacuum. The chamber 194 may be applied in a circular shape around the needle tube 190 to pinch and grasp the sclera 2 and lift a portion of the sclera 2 upward. The vacuum in the chamber 194 may create a seal on the outer surface of the sclera 2, allowing the chamber 194 to grasp a portion of the sclera 2.

[0059] 23A-23C depict another embodiment in which the needle 12 can be connected to the needle hub 112. The tubular shaft 14 can include a lever 200 and a stop 202. The lever 200 and stop 202 can be disposed at the proximal end of the tubular shaft 14. The distal end of the tubular shaft 14 can include a pair of arms 204. The distal-most tip 18 of the needle 12 can be pointed to penetrate the sclera 2. FIG. 23A shows the device prior to injection. During injection ( FIG. 23B ), the lever 200 can be actuated to push the tubular shaft 14 through the needle 12 and into the SCS 4. The lever 200 can push the tubular shaft until the stop 202 is flush with the needle hub 112 to seal the device during delivery. Once inserted, the arms 204 can mechanically separate the sclera 2 and choroid 6, guiding the drug outward from the injection site into the SCS 4. Once injection is complete (FIG. 23C), the lever 200 can be pulled upward to remove the arm 204 from the ocular tissue layer. In some examples, the arm 204 can be formed of a hydrogel thread and configured to detach from the tubular shaft 14 when positioned within the SCS 4. The arm 204 can be loaded with a drug that is released upon hydration. The arm 204 can be hydrated by injecting a hydrating solution near the arm 204, or can be naturally hydrated over time by exposure to naturally occurring fluids in the eye.

[0060] 24-27 depict an embodiment of the present disclosure in which a needle 12 may be connected to a needle hub 112. The device includes a housing 240. The housing 240 has a cylindrical shape and may house the needle hub 112 and any additional components that may be connected to the needle hub 112, such as a syringe, a connector 260 (e.g., a luer lock adapter on a syringe), or a spring 250. Referring to FIG. 24 , the housing 240 may house a piston 252, a plunger rod 242 at the proximal end of the housing 240, an indicator 246, and a feedback mechanism 248. The spring 250 may be aligned with the needle 12 so that it provides resistance as the user inserts the needle 12 through the sclera. Once the needle 12 is inserted through the sclera, the spring force decreases, providing a signal to the user indicating that the user should stop inserting the needle 12. The signal may be the indicator 246 or any suitable signal. For example, the indicator 246 may be an LED light source or an audible noise. The feedback mechanism 248 may be a stop or brake that prevents the spring 250 from pushing the needle hub 112 past a preset limit of the housing 240. In some examples, the needle hub 112 may be configured to simply return toward the proximal end of the housing 240 without moving toward the distal-most tip of the housing 240. The device may also include an outer shaft 280 ( FIGS. 26A and 26B ) that can snap onto the needle hub 112. Alternatively, the outer shaft 280 may be attached directly to the needle 12. The outer shaft 280 may have a cylindrical shape that surrounds at least a portion of the needle 12. In some embodiments, the outer shaft 280 may be formed of a transparent material, allowing the user to view the needle 12 through the outer shaft 280. This may allow the user to more easily confirm the placement of the needle 12 during injection. The distance between the distal end of the outer shaft 280 and the distal-most tip of the needle 12 (denoted by B in FIG. 26A) can be used to control the depth of needle insertion. Distance B can be adjustable.For example, the outer shaft 280 can have a threaded component that defines the distance B, can include a mechanism that makes the distance B adjustable, can have markings, e.g., color coding, that indicate to the user the length of the distance B, or can be a disposable component. In some examples, several outer shafts 280 may be provided to the user, each providing a different distance B so that the user can select the appropriate shaft component based on an estimate of the patient's scleral thickness. In another example, the outer shaft 280 can have an angled edge ( FIG. 26B ) to allow needle insertion at a desired angle. In another example, the device can operate automatically, such that the needle 12 is inserted into the eye until a feedback mechanism 248 (shown in FIG. 24 ) prevents further insertion of the needle 12. Such automatic operation can improve control of the needle 12 and provide greater control over the overall injection rate. In yet another example, the outer shaft 280 may be formed similarly to the adapter 290 (shown in FIGS. 28-30 and described in further detail below) to include a surface that may be applied to and mate with the sclera of the patient's eye. In yet another example, the outer shaft 280 may translate relative to the needle hub 112 and needle 12 to provide audible feedback to the user. For example, translation of the outer shaft 280 may produce an audible click to the user when the translation reaches a predetermined limit. The predetermined limit may be, for example, the point at which the needle hub 112 approaches the distal end of the outer shaft 280. In yet another example, the embodiment shown in FIGS. 24-27 may be combined with any of the feedback features previously described herein to provide the user with an indication of whether the needle 12 has been inserted into the target location.

[0061] Various methods for delivering a drug to the SCS of a patient's eye are disclosed throughout the description of the devices and systems herein. An example of using an instrument 10 to deliver a drug to the suprachoroidal space of a patient's eye is shown in FIGS. 27A and 27B . The instrument 10 can be inserted from an injection site 24 so that the distal-most tip 18 of the needle 12 can cut a portion of the sclera 2. Once the instrument 10 is within the SCS 4, the tubular shaft 14 can be inserted into the SCS 4 until it reaches a certain distance from the insertion site 24 and expands a portion of the sclera 2 and / or choroid 6, thereby increasing the area of ​​the SCS 4 ( FIG. 27A ). Once the tubular shaft 14 is inserted into the SCS 4, a quantity of drug can be injected into the area of ​​the SCS 4. The tubular shaft 14 can be retractable, as shown in FIG. 27B . As the tubular shaft 14 is retracted, a quantity of drug can be simultaneously injected through the tubular shaft 14 into the region of the SCS 4 such that the drug resides within the lumen left by the tubular shaft 14. The instrument 10, needle 12, and tubular shaft 14 can include any of the components described above.

[0062] The methods disclosed herein can be pressure-controlled. For example, the infusion or pouring rate can be based on pressure feedback. The pressure within the SCS can be limited to prevent an increase in pressure level that could cause damage to ocular tissue in the eye. Pressure-controlled infusion can also allow for a longer duration of drug delivery from an infusion site within the SCS. In other examples, the apparatus and / or devices described herein can be connected to a pump / electromechanical device that can monitor the pressure of the entire system. Pressure-controlled infusion can also control the flow rate of the drug into the SCS so that the pressure of the flow does not exceed a certain pressure (e.g., intraocular lens pressure).

[0063] 28-30 , the systems and methods described herein may include an adapter 290. The adapter 290 may be a component configured to surround the shaft of the needle 12. The adapter 290 may be positioned toward the distal-most tip 18 relative to the needle hub 112 to which the needle 12 may be connected. In another configuration, the needle 12 is connected to a container (not shown) for a medication, such as a syringe. In some examples, the needle 12 may be a staked needle. In other examples, the needle hub 112 may be positioned between the container (not shown) and the needle 12. The adapter 290 may include an intermediate surface 292 that defines a substantially cylindrical portion of the adapter 290. When the adapter 290 is positioned to surround a portion of the needle 12, the longitudinal axis of the substantially cylindrical portion of the adapter 290 may extend parallel to the longitudinal axis of the needle 12. For purposes of this disclosure, the longitudinal axis of the substantially cylindrical portion shall be understood to be the longitudinal axis of the adapter 290.

[0064] Adjacent the mid-surface 292, the adapter 290 can include an angled distal surface 294 disposed relative to the mid-surface 292 toward the distal end of the adapter 290. The angled distal surface 294 can define a substantially frusto-conical portion or a partially frusto-conical portion of the adapter 290. The angled distal surface 294 can be oriented, for example, at an angle ranging from about 30 degrees to about 60 degrees relative to the longitudinal axis of the adapter 290, at an angle ranging from about 40 degrees to about 50 degrees relative to the longitudinal axis of the adapter 290, or at an angle of about 45 degrees relative to the longitudinal axis of the adapter 290.

[0065] The adapter 290 may further include an outermost beveled surface 298. The outermost beveled surface 298 may be a flat surface adjacent to the intermediate surface 292 and / or the angled distal surface 294. Alternatively, the outermost beveled surface 298 may be a convex surface configured to rest against and mate with the sclera of the patient's eye. As shown in FIG. 29 , the outermost beveled surface 298 may be oriented at an angle θ relative to the longitudinal axis of the adapter 290. The angle θ may range from about 25 degrees to about 75 degrees relative to the longitudinal axis of the adapter 290, from about 40 degrees to about 65 degrees relative to the longitudinal axis of the adapter 290, or from about 30 degrees to about 60 degrees relative to the longitudinal axis of the adapter 290. In an exemplary embodiment, the angle θ may be about 45 degrees relative to the longitudinal axis of the adapter 290.

[0066] The outermost beveled surface 298 can be configured in various ways to achieve contact with the sclera of the patient's eye. For example, the outermost beveled surface 298 can be smooth or polished to minimize abrasion on the sclera. Alternatively, the outermost beveled surface 298 can be roughened to minimize movement of the adapter 290 relative to the sclera. In some embodiments, the outermost beveled surface 298 can include geometric features such as protruding indentations, recessed indentations, undulations, other geometric features, or any combination thereof. Additionally, a coating can be applied to the outermost beveled surface 298. The coating can be therapeutic, antibacterial, and / or sterilizing. As another example, the outermost beveled surface 298 can be formed by overmolding a material onto the adapter 290. The overmolded material can be selected, for example, based on its surface characteristics (e.g., rough, smooth, etc.) or its compatibility with surface finishes such as polishing. The outermost beveled surface 298 may further incorporate various combinations of the aforementioned features, such as a polished surface with geometric features, a roughened surface with geometric features, an overmolded material with a coating, etc. While exemplary combinations of features are described herein, these combinations are not limiting and other combinations are contemplated.

[0067] The adapter 290 may include a visual indication of the position of the adapter 290 and / or the outermost beveled surface 298. For example, the outermost beveled surface 298 may be colored differently from other surfaces of the adapter 290 to distinguish the outermost beveled surface 298 from the other surfaces. The adapter 290 may also include visible markings to indicate the position of the adapter 290 and / or the outermost beveled surface 298. Such visible markings may include contrasting color markings, texture markings, etc. on the outermost beveled surface 298 and / or on other surfaces of the adapter 290. The visible markings may be applied to the adapter 290 using silkscreening, overmolding, etching, or a variety of other suitable techniques. The visible markings may be any geometric shape, including a circle, an ellipse, a polygon, an irregular shape, or any combination thereof.

[0068] The adapter 290 can include a proximal surface 295 and a distal surface 296. The proximal surface 295 can be a substantially circular surface that is adjacent to the mid-surface 292 and lies in a plane perpendicular to the longitudinal axis of the adapter 290. The distal surface 296 can also be a substantially circular surface. The distal surface 296 can be adjacent to the angled distal surface 294 and lies in another plane perpendicular to the longitudinal axis of the adapter 290. Thus, the proximal surface 295 can be parallel to the distal surface 296.

[0069] The adapter 290 may include a needle bore 302 in which the needle 12 can be disposed. The needle bore 302 may extend parallel or substantially parallel to the longitudinal axis of the adapter 290. When disposed within the needle bore 302, the needle 12 may intersect with each of the proximal and distal faces 295 and 296. When disposed within the needle bore, the distal-most tip 18 of the needle 12 may extend a distance C from the distal face 296. The length of the distance C may be such that the bevel 18a of the distal-most tip 18 can extend from the distal face 296. The length of the distance C may also be such that a portion of the shaft of the needle 12 proximal to the distal-most tip 18 can extend from the distal face 296. Distance C can be, for example, between 200 μm and 1200 μm, between 400 μm and 1000 μm, between 600 μm and 800 μm, or about 700 μm. In some embodiments, beveled surface 18 a and outermost beveled surface 298 can be oriented at the same angle relative to the longitudinal axis of adapter 290.

[0070] The adapter 290 may be selectively translatable relative to the needle 12 along the longitudinal axis of the needle 12. Translation of the adapter 290 may be desirable, for example, to adjust the distance C. For use, the adapter 290 may be secured to the needle 12. The adapter 290 may be connected to the needle 12 by any suitable means, including screws, fasteners, nuts, bolts, or adhesives. By way of example and as shown in FIGS. 28-30 , the adapter 290 may be secured to the needle 12 using a screw 288. The screw 288 may be inserted into a threaded bore 304 within the adapter 290. When tightened, the screw 288 may exert a force on the needle 12 perpendicular to the longitudinal axis of the needle 12. This force may create longitudinal friction between the needle 12 and the screw 288, as well as between the needle 12 and the needle bore 302, thereby preventing the adapter 290 from translating relative to the needle 12. If a user wishes to adjust the distance C, for example, to extend the distance of the distal-most tip 18 from the distal surface 296, the user can loosen the bolt to allow the adapter 290 to translate relative to the needle 12. As shown in FIG. 30 , the adapter 290 can be used to guide the trajectory of the distal-most tip 18 of the needle 12 through the sclera 2 and into the SCS 4. To inject a medication into the SCS 4, the user can, for example, penetrate the sclera 2 with the distal-most tip 18 and insert the needle 12 through the sclera 2. The user can angle the needle 12 so that the outermost beveled surface 298 is oriented parallel to a plane tangent to the outer surface of the sclera 2. In this case, the user can continue to insert the needle 12 until the outermost beveled surface 298 contacts the surface of the sclera 2. In an exemplary method in which the outermost beveled surface 298 is a flat surface, the user can insert the needle 12 until the outermost beveled surface 298 contacts the surface of the sclera 2. In an exemplary method in which the outermost beveled surface 298 is convex, the user can insert the needle 12 until the outermost beveled surface 298 interfaces with the surface of the sclera 2. When the outermost beveled surface 298 contacts the sclera 2, the needle 12 is prevented from being inserted further and may possibly be prevented from penetrating the choroid 6.

[0071] In some embodiments, the user can adjust the distance C to a desired length by translating the adapter 290 along the needle 12. When the user has adjusted the distance C and / or the angle θ as desired, the user can use the adapter 290 to guide the trajectory of the needle 12 into the SCS 4 so that the needle 12 penetrates the sclera 2 to a substantially predetermined depth. This may allow the user to inject the medication into the suprachoroidal space 4 with some precision without penetrating the choroid 6.

[0072] As shown in FIGS. 28-30 , the adapter 290 may be positioned near the needle 12. Alternatively, the adapter 290 may be attached to either or both the hub 112 and a medication container (e.g., a syringe) connected to the needle 12. For example, the adapter 290 may be attached to the hub 112 in a manner similar to the outer shaft 280 shown in FIGS. 26A and 26B . Additionally, the adapter 290 may be spring-loaded such that the spring urges the adapter 290 toward the distal-most tip 18. In use, a user places the adapter 290 against the patient's sclera and exerts sufficient force to depress the spring, thereby exposing the needle 12. The spring can be configured to control the depth of penetration of the needle 12 into the patient's eye.

[0073] The adapter 290 may be made of any suitable metal, polymer, and / or combination of metal and / or polymer. Exemplary metal materials may include stainless steel, nitinol, titanium, and / or alloys of these metals. Exemplary polymer materials may include polyetheretherketone (PEEK), polyimide, and polyethersulfone (PES). In some examples, the adapter 290 may be made of a rigid material, a semi-rigid material, or a flexible material. The adapter 290 may also be formed of any biocompatible material that can be sterilized. In some examples, the adapter 290 may be made of a transparent material to allow easier identification of and / or navigation of the blood vessels in the patient's eye.

[0074] It should be understood that the dimensions of the adapter 290 are not limited and may, in fact, vary. For example, the length of the adapter 290 (i.e., the distance between the proximal and distal faces 295 and 296) may vary to accommodate needles of different lengths. The diameter of the needle bore 302 may also vary to accommodate needles having different diameters. Furthermore, the diameter of the proximal and / or distal faces 295 and 296 may also vary.

[0075] As described herein, the adapter 290 can be useful for reducing human error in ocular injection procedures. In addition to being useful for injection into the suprachoroidal space, the adapter 290 can also be useful for injection into other cavities of the eye, such as the subretinal space. Current methods for subretinal drug delivery can be invasive and require additional surgery. Surgical procedures for subretinal drug delivery may require creating a breach in the retinal surface and / or a complete vitrectomy to allow a cannula to access the subretinal space. Alternatively, the adapter 290 can allow access to the subretinal space through the sclera, thereby reducing the invasiveness of the procedure. Using ocular imaging techniques such as optical coherence tomography (OCT) and / or ultrasound, the precise distance between the surface of the sclera and the subretinal space can be calculated. The distance between the distal-most tip 18 of the needle 12 and the distal surface 296 or outermost bevel 298 of the adapter 290 can be configured to match the distance between the sclera and the subretinal space. In such a configuration, the adapter 290 can prevent the needle 12 from extending beyond the subretinal space into the vitreous. The outermost beveled surface 298 can also control the angle at which the subretinal injection is made.

[0076] The adapter 290 can be formed by any suitable manufacturing process, including, but not limited to, milling, CNC machining, polymer casting, rotational molding, vacuum forming, injection molding, extrusion molding, blow molding, or any combination thereof.

[0077] The various devices and components described herein can be provided as kits for practicing one or more methods described herein. For example, a syringe, a needle, an adapter, and a quantity of ophthalmic medication can be provided in a blister pack. Each of the syringe, needle, adapter, and ophthalmic medication can be sterilized and then sealed in a blister pack. In some embodiments, the kit can include multiple adapters. The multiple adapters can have various dimensions to allow a user to select an adapter that best fits the patient's anatomy and / or to control the needle penetration angle or depth. The multiple adapters can also be formed from various materials to allow a user to select an adapter with the appropriate material for a particular procedure and / or patient. In some embodiments, a syringe can contain an ophthalmic medication. The nominal maximum fill volume of the syringe can be between about 0.5 mL and about 1.0 mL. In various methods described herein, the amount of medication (e.g., ophthalmic medication) delivered to a patient can range from about 50 μL to about 500 μL.

[0078] Various drugs and drug formulations may be used with the embodiments of the present disclosure. As one example, the embodiments described herein may be used to inject a drug in the form of a delayed-release pellet. The drug can be released from the pellet when the pellet is hydrated, and this release may be achieved by exposing the pellet to ocular fluid, by injecting a separate hydration fluid, or a combination of the foregoing. A separate hydration fluid, such as saline, may be injected before, after, or simultaneously with the pellet. As another example, the embodiments described herein may be used to inject multiple substances sequentially. A first substance may be injected to expand a target ocular cavity, such as the suprachoroidal space, and then a second substance may be injected into the expanded suprachoroidal space. The first substance may be, for example, saline, and the second substance may be, for example, a drug in the form of a viscous gel. As yet another example, a sponge-like material may be first injected or inserted into the target ocular cavity. The sponge-like material may be configured to release the drug over a period of time. The sponge-like material can be further recharged or resoaked with drug by subsequent injections of the drug.

[0079] Embodiments of the present disclosure may further include additional features to improve injection accuracy. As one example, embodiments described herein may include a light source, such as an LED light source, configured to illuminate the injection site. As another example, embodiments described herein may include a needle formed in whole or in part from a magnetic material or that otherwise includes a magnetic element. A magnet positioned outside the patient's eye, e.g., held by the user, may be used to guide the needle to the target injection site. The magnet may also be used to pull, i.e., apply a magnetic force to, the needle to prevent it from penetrating beyond a desired depth. As yet another example, embodiments described herein may include a mechanism configured to sense the angle of the needle relative to the eye. This mechanism may include a sensor that can be calibrated according to the patient's scleral thickness. Scleral thickness may be measured using optical coherence topography (OCT), ultrasound, or any other suitable technique. This mechanism may be configured to provide feedback to the user, such that the user can be alerted to continue advancing the needle if it is oriented at the appropriate angle relative to the eye. If the needle is not oriented at the proper angle relative to the eye, the user may be warned to stop advancing the needle and adjust the needle orientation.

[0080] In embodiments of the present disclosure, needle 12 can be a first needle, and the devices, apparatus, and / or kits disclosed herein can include a second needle. The first and second needles can be interchangeable. Thus, needle 12 can be interchangeable.

[0081] Listed below are further illustrative embodiments according to the present disclosure. (1) A system for delivering a drug to the suprachoroidal space of an eye, the system comprising a needle having a passageway and a sharp distal-most tip, and a device configured to manipulate the sclera to enable delivery of the drug to the suprachoroidal space of the eye.

[0082] (2) The system of (1), wherein the needle is configured to deliver the drug to the suprachoroidal space of the eye. (3) A system according to (1), wherein the pointed distal-most tip includes multiple openings.

[0083] (4) A system according to (3), wherein the opening comprises a circular structure. (5) The system of (3), wherein the opening comprises a slot. (6) The system of (3), wherein the plurality of openings are present around and along at least a portion of the entire length of the pointed, most distal tip.

[0084] (7) The system of (1), wherein the device is configured to deliver the drug to the suprachoroidal space of the eye. (8) The system of (1), wherein the device is positioned within the needle passageway and is longitudinally translatable relative to the needle.

[0085] (9) The system of (8), wherein the device includes a tubular shaft having a distal end, the tubular shaft comprising a rigid, semi-rigid, or flexible material. (10) The system of (9), wherein the distal end includes an atraumatic distal tip.

[0086] (11) The system of (10), wherein the atraumatic distal tip includes multiple openings. (12) The system of (11), wherein the opening includes a circular structure. (13) The system of (11), wherein the opening comprises a slot.

[0087] The system of (11), wherein a plurality of openings are present around the circumference and at least a portion of the entire length of the atraumatic distal tip. (15) The system of (9), wherein the distal end includes an expandable member.

[0088] (16) The system of (15), wherein the expandable member comprises a stent. (17) The system of (10), wherein the tubular shaft includes an expandable portion. (18) The system of (17), wherein the expandable portion includes a pair of curved arms located proximal to the atraumatic distal tip.

[0089] (19) The system of (9), wherein the tubular shaft includes a cross-sectional dimension that is smaller than the cross-sectional dimension of the passageway. (20) The system of (9), wherein the outer surface of the tubular shaft includes one or more channels.

[0090] (21) The system of (9), wherein the distal end of the tubular shaft includes at least two legs configured to selectively diverge when the distal end of the tubular shaft is deployed from the needle passageway. (22) A system of (1) in which the needle is curved.

[0091] (23) The system of (1), wherein the needle is U-shaped. (24) The system of (1), wherein the device comprises a flat surface having protrusions for deforming one or more of the sclera or choroid.

[0092] (25) A system of (24) in which the protrusion is a rounded surface. (26) The system of (1), wherein the device includes a chamber configured to retract a portion of the sclera.

[0093] (27) The system of (26), wherein the device is configured to apply suction force to the sclera. (28) The system of (27), wherein the needle is disposed within the chamber.

[0094] (29) The system of (27), wherein the chamber includes a stop configured to limit proximal advancement of the sclera into the chamber. (30) The system of (29), wherein the stopper is configured to surround the needle.

[0095] (31) The system of (29), wherein the stopper includes a plurality of extensions extending from the sidewall of the chamber toward the center of the chamber. (32) The system of (29), wherein the stop includes a plurality of openings configured to allow application of suction force to the sclera.

[0096] (33) The system of (26), wherein the chamber comprises a circular cross-sectional structure. (34) The system of (26), wherein the chamber comprises a semicircular cross-sectional structure. (35) The system of (1), wherein the needle includes a bent portion located proximal to the sharp, distal-most tip.

[0097] (36) The system of (1), wherein the needle includes an outer surface having a plurality of geometric features configured to provide tactile feedback to the user. (37) The system of (9), wherein the distal end includes an anchor.

[0098] (38) The system of (37), wherein the anchor has a curved, flat, or atraumatic shape. (39) A device for manipulating the sclera to enable delivery of a drug to the suprachoroidal space of the eye, the device comprising: a tubular shaft having a distal end, the tubular shaft comprising a rigid, semi-rigid, or flexible material; and a needle having a passageway and a sharp, distal-most tip, the device being disposed within the needle.

[0099] (40) The device of (39), wherein the needle is configured to deliver the drug to the suprachoroidal space of the eye. (41) The device described in (39), wherein the pointed distal-most tip includes multiple openings.

[0100] (42) The device of (41), wherein the opening comprises a circular structure. (43) The device of (41), wherein the opening includes a slot. (44) The device of (41), wherein the plurality of openings are present around and along at least a portion of the entire length of the pointed, most distal tip.

[0101] (45) The device of (39), wherein the device is configured to deliver the drug to the suprachoroidal space of the eye. (46) The device of (39), wherein the device is longitudinally translatable relative to the needle.

[0102] (47) The device of (39), wherein the distal end includes an atraumatic distal tip. (48) The device of (47), wherein the atraumatic distal tip includes multiple openings. (49) The device of (48), wherein the opening comprises a circular structure.

[0103] (50) The device of (48), wherein the opening includes a slot. (51) The device of (48), wherein a plurality of openings are present around and along at least a portion of the length of the atraumatic distal tip.

[0104] (52) The device of (39), wherein the distal end includes an expandable member. (53) The device of (52), wherein the expandable member comprises a stent. (54) The device of (39), wherein the tubular shaft includes an expandable portion.

[0105] (55) The device of (54), wherein the expandable portion includes a pair of curved arms located proximal to the distal end. (56) The apparatus of (39), wherein the tubular shaft includes a cross-sectional dimension that is smaller than the cross-sectional dimension of the passageway.

[0106] (57) The device of (39), wherein the outer surface of the tubular shaft includes one or more channels. (58) The device of (39), wherein the distal end of the tubular shaft includes at least two legs configured to selectively diverge when the distal end of the tubular shaft is deployed from the needle passageway.

[0107] (59) A device as in (39) in which the needle is curved. (60) The device of (39), wherein the distal end includes an anchor. (61) The device of (60), wherein the anchor has a curved, flat, or atraumatic shape.

[0108] (62) A device for manipulating the sclera to enable delivery of a drug to the suprachoroidal space of the eye, the device comprising a flat surface having protrusions for deforming one or more of the sclera or choroid.

[0109] (63) The device of (62), wherein the protrusion has a rounded surface. (64) A device for treating the sclera to enable delivery of a drug to the suprachoroidal space of the eye, the device comprising a chamber configured to retract a portion of the sclera.

[0110] (65) The device of (64), wherein the device is configured to apply a suction force to the sclera. (66) The device of (64), wherein the needle is disposed within the chamber.

[0111] (67) The device of (66), wherein the chamber includes a stop configured against proximal advancement of the sclera into the chamber. (68) The device of (67), wherein the stopper is configured to surround the needle.

[0112] (69) The device of (67), wherein the stopper includes a plurality of extensions extending from the sidewall of the chamber toward the center of the chamber. (70) The device of (67), wherein the stop includes a plurality of openings configured to allow application of suction force to the sclera.

[0113] (71) The apparatus of (67), wherein the chamber comprises a circular cross-sectional structure. (72) The apparatus of (67), wherein the chamber comprises a semicircular cross-sectional structure. (73) A device for preparing the sclera to allow delivery of a drug to the suprachoroidal space of the eye, the device comprising a needle tube having a cylindrical shape and a serrated needle tip.

[0114] (74) A device as described in (73) in which the tip of a serrated needle vibrates to cut open a portion of the sclera. (75) A device for treating the sclera to enable delivery of a drug to the suprachoroidal space of the eye, the device comprising: a needle having a sharp distal-most tip; a needle hub connected to the proximal end of the needle; and a housing surrounding the needle hub and extending from the proximal end of the needle hub.

[0115] (76) The device of (75), wherein the housing is cylindrical. (77) The device of (75), wherein the housing includes an additional component selected from a syringe, a spring, a piston, a plunger rod, an indicator, a feedback mechanism, or a combination thereof.

[0116] (78) The device of (75), further comprising a shaft surrounding a portion of the needle and extending from the distal end of the needle hub. (79) The device of (78), wherein the distal end of the shaft is angled to allow for oblique needle insertion.

[0117] (80) A method for delivering a drug to the suprachoroidal space of an eye, comprising: treating one of the sclera and choroid layers of the eye to increase the size of the suprachoroidal space; advancing a distal end of a drug delivery device to the suprachoroidal space; positioning a distal-most tip of the drug delivery device within the suprachoroidal space; and delivering a quantity of drug to the suprachoroidal space.

[0118] (81) The method of (80), wherein the step of advancing the distal end of the drug delivery device to the suprachoroidal space includes penetrating the sclera. (82) The method of (80), wherein the step of positioning the distal-most tip of the drug delivery device includes placing the distal-most tip in the suprachoroidal space without contacting the choroid.

[0119] (83) The method of (80), wherein the step of positioning the distal-most tip of the drug delivery device includes the step of placing the distal-most tip in the suprachoroidal space without perforating the outermost surface of the choroid. (84) The method of (80), wherein the step of positioning the distal-most tip of the agent includes the step of placing the distal-most tip within the suprachoroidal space without penetrating a thickness of the choroid.

[0120] (85) The method of (80), wherein the amount of the drug delivered to the suprachoroidal space is about 50 μL to 500 μL. (86) The method of (80), wherein the delivery of the amount of drug to the suprachoroidal space is pressure controlled.

[0121] (87) The method of (80), wherein treating one of the sclera and choroid layers comprises rotating the drug delivery device. (88) The method of (80), wherein the step of treating one of the sclera and choroid layers includes the step of tensioning the sclera layer to increase the size of the suprachoroidal space.

[0122] (89) The method of (80), wherein the step of delivering the amount of medicinal solution to the suprachoroidal space includes the step of delivering the amount from the most distal tip of the medicinal solution delivery device. (90) The method of (80), wherein the step of delivering the amount of drug to the suprachoroidal space comprises delivering the drug from a location proximal to the distal-most tip of the drug delivery device.

[0123] (91) A device for enabling directed delivery of a drug into a human organ of a patient, the device comprising: a container for the drug fluidly connected to a needle, the needle having a needle shaft and a sharp distal-most tip having a bevel, the needle connected to a distal end of the container; and an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharp distal-most tip of the needle, the adapter including an outermost beveled surface configured to guide the trajectory of the sharp distal-most tip to a predetermined depth and location within the human organ, the outermost beveled surface facing in the same direction as the bevel of the sharp distal-most tip, the angle of the outermost beveled surface dictating the trajectory of the needle, and the length of the needle extending from the outermost beveled surface determining the depth and location of drug delivery.

[0124] (92) The device of (91), wherein the sharp distal-most tip is a portion of a needle extending from the distal end of the adapter. (93) The device of (91), further comprising a needle hub shaft connected to the proximal end of a needle, such as a needle needle.

[0125] (94) The device of (91), further comprising a hub disposed between the container and the needle. (95) The device of (94), wherein the needle is removably connected to the hub. (96) The device of (95), wherein the needle is a first needle and the device further comprises a second needle.

[0126] (97) The device of (96), wherein the first needle and the second needle are interchangeable. (98) The device of (91), wherein the needle is replaceable. (99) The device of (91), wherein the angle is in the range of about 25 degrees to about 75 degrees.

[0127] (100) The device of (91), wherein the angle is in the range of about 40 degrees to about 60 degrees. (101) The apparatus of (91) wherein the angle is about 45 degrees. (102) The device of (91), wherein the adapter is connected to a portion of the needle shaft via a fastener or screw.

[0128] (103) The device of (102), wherein the adapter is translatable relative to the axial path of the needle shaft. (104) The device of (91), wherein the adapter is attached to the needle shaft via adhesive.

[0129] (105) The device of (91), wherein the adapter includes a proximal end having a surface extending in a first plane perpendicular to the needle, an angled distal side, an intermediate surface extending between the proximal end and the angled distal side, the intermediate surface extending in a second plane perpendicular to the first plane, and a distal end, the distal end including a substantially flat surface extending in a third plane parallel to the first plane.

[0130] (106) The apparatus of (91), wherein at least a portion of the adapter comprises a substantially cylindrical cross section. (107) The device of (91), wherein the outermost inclined surface is angled relative to the longitudinal axis of the adapter.

[0131] (108) The device of (91), wherein the sharp distal-most tip of the needle has a length in the range of about 600 μm to about 800 μm. (109) The device of (91), wherein the outermost inclined surface is a flat surface.

[0132] (110) The device of (91), wherein the outermost inclined surface is a convex surface configured to mate with the outer surface of the eye. (111) A system for delivering a medication to a patient's ocular cavity, comprising: a syringe having a nominal maximum fill volume of between about 0.5 mL and about 1.0 mL; a needle having a needle shaft and a sharpened distal-most tip having a bevel; and an adapter surrounding a portion of the needle shaft along its longitudinal axis, the adapter including an outermost bevel that is angled relative to the longitudinal axis of the adapter and configured to guide the trajectory of the sharpened distal-most tip to a predetermined ocular depth and location, wherein the syringe, needle, and adapter are sterilized and contained within a blister pack.

[0133] (112) The system of (111), wherein the adapter is configured to limit advancement of the sharp distal-most tip into the suprachoroidal space of the eye. (113) The system of (111), wherein the sharp distal-most tip is a portion of the needle extending from the outermost bevel.

[0134] (114) The system of (111), wherein the angle of the outermost inclined surface is in the range of about 25 degrees to about 75 degrees. (115) The system of (111), wherein the angle of the outermost inclined surface is in the range of about 40 degrees to about 60 degrees.

[0135] (116) The system of (111) in which the angle of the outermost inclined surface is about 45 degrees. (117) The system of (111), wherein the sharp distal-most tip of the needle has a length in the range of about 600 μm to about 800 μm.

[0136] (118) A kit for treating a patient with an ophthalmic disease, comprising: a syringe having a nominal maximum fill volume of between about 0.5 mL and about 1.0 mL; a needle having a needle shaft and a sharp distal-most tip; an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharp distal-most tip of the needle, the adapter including an outermost beveled surface configured to guide the trajectory of the sharp distal-most tip to a predetermined depth and position in the eye; and an ophthalmic medication.

[0137] (119) A kit for treating a patient with an ophthalmic disease, comprising: a syringe prefilled with an ophthalmic medication, the syringe containing an amount of the ophthalmic medication in a range between about 0.5 mL and about 1.0 mL; a needle having a needle shaft, a passageway, and a sharp distal-most tip; and an adapter surrounding a portion of the needle shaft along a longitudinal axis of the needle shaft, excluding the sharp distal-most tip, the adapter including an outermost beveled surface configured to guide the trajectory of the sharp distal-most tip to a predetermined depth and position in the eye.

[0138] (120) A method of delivering a medication to a patient's eye, comprising positioning a distal-most tip of a medication delivery device within the suprachoroidal space of the eye at a predetermined ocular depth and location, the medication delivery device comprising: a container for the medication fluidly connected to a needle, the needle comprising a needle shaft and a sharp distal-most tip having a bevel, the needle connected to a distal end of the container; and an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the sharp distal-most tip of the needle, the adapter including an outermost bevel configured to guide the trajectory of the sharp distal-most tip to the predetermined ocular depth and location, the method further comprising delivering a quantity of medication to the suprachoroidal space.

[0139] (121) A method of delivering a drug to the suprachoroidal space of an eye using a drug device, the drug device comprising: a container for the drug fluidly connected to a needle, the needle comprising a needle shaft and a sharp, distal-most tip having a bevel; and an adapter surrounding a portion of the needle shaft along its longitudinal axis, the adapter including an outermost beveled surface angled relative to the longitudinal axis, the method comprising penetrating the sharp, distal-most tip into the sclera of the eye; inserting the needle through the sclera into the suprachoroidal space until the outermost beveled surface contacts the sclera; and delivering a quantity of the drug to the suprachoroidal space when the outermost beveled surface contacts the sclera.

[0140] (122) A method for delivering a drug to the suprachoroidal space of an eye, comprising: treating one of the sclera or choroid layers of the eye to increase the size of the suprachoroidal space; advancing a distal end of a drug delivery device to the suprachoroidal space; positioning a distal-most tip of the drug delivery device within the suprachoroidal space; and delivering a quantity of drug to the suprachoroidal space.

[0141] (123) The method of (122), wherein the step of advancing the distal end of the drug delivery device to the suprachoroidal space includes penetrating the sclera. (124) The method of (122), wherein the step of positioning the distal-most tip of the drug delivery device includes placing the distal-most tip in the suprachoroidal space without contacting the choroid.

[0142] (125) The method of (122), wherein the step of positioning the distal-most tip of the drug delivery device includes the step of placing the distal-most tip in the suprachoroidal space without perforating the outermost surface of the choroid. (126) The method of (122), wherein the step of positioning the distal-most tip of the agent includes the step of placing the distal-most tip within the suprachoroidal space without penetrating a certain thickness of the choroid.

[0143] (127) The method of (122), wherein the amount of the drug delivered to the suprachoroidal space is about 50 μL to 500 μL. It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed devices and methods without departing from the scope of the disclosure. Other aspects of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the features disclosed herein. The specification and examples should be considered as illustrative only.

Claims

1. 1. A device for delivering a drug into a human organism, comprising: a container configured to contain a medicament and connected to a needle, the needle including a needle shaft and a distal tip, the needle connected to a distal end of the container; an adapter surrounding a portion of the needle shaft along its longitudinal axis but not including the distal tip, the adapter including a beveled surface configured to guide the trajectory of the distal tip to a predetermined depth within a human organ; The device, wherein the beveled surface is angled relative to a longitudinal axis of the needle.

2. The device of claim 1 , wherein the needle shaft extends through a distal face of the adapter, the distal face of the adapter being perpendicular to the longitudinal axis.

3. The device of claim 1 , wherein the needle shaft extends through the beveled surface.

4. The device of claim 1 , wherein the angle between the angled surface and the longitudinal axis ranges from about 25 degrees to about 75 degrees.

5. The device of claim 1 , wherein the angle between the angled surface and the longitudinal axis is in the range of about 40 degrees to about 60 degrees.

6. The device of claim 1 , wherein the adapter is selectively translatable to a plurality of positions along the longitudinal axis.

7. the adapter is connected to a portion of the needle shaft via a fastener or thread; The device of claim 1 , wherein the adapter is translatable to a plurality of positions along the longitudinal axis when the fastener or screw is in a loose configuration.

8. The adapter is a proximal surface perpendicular to the longitudinal axis; a distal surface parallel to the proximal surface; The device of claim 1 , further comprising an intermediate surface extending between the proximal surface and the distal surface.

9. The adapter is a proximal surface perpendicular to the longitudinal axis; a distal surface parallel to the proximal surface; an intermediate surface extending between the proximal surface and the distal surface; The device of claim 1 , wherein the intermediate surface extends circumferentially around the longitudinal axis.

10. The device of claim 1 , wherein the angled surface is configured to interface with an outer surface of the eye.

11. 10. The device of claim 1, wherein the distal tip is located a first distance from the adapter, the first distance defining a penetration depth of the distal tip into a human organ.

12. The device of claim 1 , wherein the medication is contained within the container, the medication comprising an ophthalmic medication.

13. further comprising a needle hub connected to the proximal end of the needle; The device of claim 1 , wherein the adapter is connected to the needle hub.

14. The device of claim 1 , wherein the adapter is directly connected to the needle shaft.

15. The device of claim 1 , further comprising a spring configured to bias the adapter toward the distal tip.

16. 1. A kit for treating a patient suffering from an eye disease, comprising: The device of claim 1; an ophthalmic medication in an amount ranging from about 0.5 mL to about 1.0 mL.

17. 1. A kit for treating a patient suffering from an eye disease, comprising: The device of claim 1; a second adapter configured to direct the trajectory of the distal tip to a second predetermined depth, the second predetermined depth being different from the predetermined depth.

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