System and method for separating layers of ocular tissue

Abstract

An intraocular injection device and methods for making and using the same, whereby the intraocular injection device comprises an annular member including an annular first wall; and a needle guide channel extending through the first wall, whereby the needle guide channel includes a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit, and whereby the needle guide channel axis can be off-set from an annular member central longitudinal axis which vertically extends through the annular member such that the needle guide channel axis does not intersect with the annular member central longitudinal axis. As to particular embodiments, the intraocular injection device can further include an annular second wall disposed in spaced-apart relation to the first wall to define a chamber therebetween.

Description

[0001] 1148P01T

[0002] SYSTEM AND METHOD FOR SEPARATING LAYERS OF OCULAR TISSUE

[0003] I. SUMMARY OF THE INVENTION

[0004] Disclosed herein are embodiments of an intraocular injection device and methods for making and using the same, the intraocular injection device comprising an annular member including an annular first wall; and a needle guide channel extending through the first wall, whereby the needle guide channel includes a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit, and whereby the needle guide channel axis can be off-set from an annular member central longitudinal axis which vertically extends through the annular member such that the needle guide channel axis does not intersect with the annular member central longitudinal axis.

[0005] As to particular embodiments, the intraocular injection device can further include an annular second wall disposed in spaced-apart relation to the first wall to define a chamber therebetween.

[0006] Naturally, further objects of the invention are disclosed throughout other areas of the specification, drawings, photographs, and claims.

[0007] II. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 shows a particular embodiment of an inventive system for separating layers of ocular tissue, including an intraocular injection device engaged with an eye, a pressure regulator, and an injector.

[0009] Figure 2 is an illustration of an eye including a cornea as well as layers of the cornea.

[0010] Figure 3A is a first perspective view of a particular embodiment of an intraocular injection device.

[0011] Figure 3B is a second perspective view of the intraocular injection device shown in Figure 3A.1148P01T

[0012] Figure 3C is a front view of the intraocular injection device shown in Figure 3A.

[0013] Figure 3D is a rear view of the intraocular injection device shown in Figure 3 A.

[0014] Figure 3E is a first side view of the intraocular injection device shown in Figure 3 A.

[0015] Figure 3F is a second side view of the intraocular injection device shown in Figure 3 A.

[0016] Figure 3G is a top view of the intraocular injection device shown in Figure 3A.

[0017] Figure 3H is a bottom view of the intraocular injection device shown in Figure 3 A.

[0018] Figure 4A is a cross-sectional view of the intraocular injection device shown in Figure 3E.

[0019] Figure 4B is a cross-sectional view of the intraocular injection device shown in Figure 3F.

[0020] Figure 5A is the top view of the intraocular injection device shown in Figure 3G, but whereby the needle of an injector is received within the needle guide channel.

[0021] Figure 5B is the cross-sectional view of the intraocular injection device shown in Figure 4A, but whereby the needle of an injector is received within the needle guide channel.

[0022] Figure 6 is the cross-sectional view of the intraocular injection device shown in Figure 4A, but whereby the intraocular injection device is engaged with an eye and the needle of an injector is received within the needle guide channel.

[0023] Figure 7A is an illustration of the central and peripheral portions of a cornea.

[0024] Figure 7B is the illustration of the central and peripheral portions of the cornea shown in Figure 7 A, whereby a cornea periphery entry location and a cornea periphery target injection location are also shown.1148P01T

[0025] Figure 7C is the illustration of the central and peripheral portions of the cornea shown in Figure 7 A, whereby a cornea center entry location and a cornea periphery target injection location are also shown.

[0026] Figure 7D is the illustration of the central and peripheral portions of the cornea shown in Figure 7 A, whereby a cornea peripheral entry location and a cornea center target injection location are also shown.

[0027] Figure 8A is a first perspective view of a particular embodiment of an intraocular injection device.

[0028] Figure 8B is a second perspective view of the intraocular injection device shown in Figure 8A.

[0029] Figure 8C is a front view of the intraocular injection device shown in Figure 8 A.

[0030] Figure 8D is a rear view of the intraocular injection device shown in Figure 8 A.

[0031] Figure 8E is a first side view of the intraocular injection device shown in Figure 8 A.

[0032] Figure 8F is a second side view of the intraocular injection device shown in Figure 8 A.

[0033] Figure 8G is a top view of the intraocular injection device shown in Figure 8 A.

[0034] Figure 8H is a bottom view of the intraocular injection device shown in Figure 8 A.

[0035] Figure 9A is a cross-sectional view of the intraocular injection device shown in Figure 8E.

[0036] Figure 9B is a cross-sectional view of the intraocular injection device shown in Figure 8F.

[0037] Figure 10A is an illustration of the generation of a type 1 bubble in the cornea.1148P01T

[0038] Figure 10B is an illustration of the generation of a type 2 bubble in the cornea.

[0039] Figure 10C is an illustration of the generation of a type 3 bubble in the cornea.

[0040] Figure 11A is an illustration of the positioning of a needle tip within the cornea to generate a type 1 bubble.

[0041] Figure 11B is an illustration of the positioning of a needle tip within the cornea to generate a type 2 bubble.

[0042] Figure 12 shows a type 1 bubble post procedure using the intraocular injection device.

[0043] Figure 13A is a microscopic image of a needle tip being inserted into a cornea via the intraocular injection device.

[0044] Figure 13B is an optical coherence topography (OCT) image of a cornea following insertion of a needle tip using the intraocular injection device.

[0045] III. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] Now referring primarily to Figure 1 which illustrates a novel system for separating layers of ocular (or eye) tissue, the system can include an intraocular injection device (1) that may assist with an injection into the eye (E), a pressure regulator (2), and an injector (3) for performing the injection into the eye (E). As to particular embodiments, the system can be useful for separating layers of the cornea (4).

[0047] Now referring primarily to Figure 2, the cornea (4) includes six layers presented anterior to posterior: the epithelium (5), Bowman’s layer (6), the stroma (7), the pre-Descemet’ s membrane (8 A) (not shown in Figure 2), the Descemet’s membrane (8B), and the endothelium (9). The epithelium (5) is the outermost layer of the surface of the eye (ocular surface), contains about 5 to about 7 layers of cells, measures about 50 microns thick, regenerates quickly, and acts as a barrier to the outside world. Bowman’ s layer (6) is a tough, acellular transition layer between the epithelium (5) and the stroma (7), and is largely involved in providing structural support to maintain the proper shape of the cornea (4); this layer measures only about 8 to about 14 microns1148P01T

[0048] thick. The stroma (7) is the bulk of the cornea (4), comprising about 90% thereof, and measures about 500 microns thick. This layer is comprised of keratocytes and collagen fibers that are extremely regular in arrangement and constant in shape; the complex, interwoven structural organization of these fibers allows for the cornea (4) to remain transparent. The pre-Descemet’s membrane (8 A) (also known as the Dua’s layer) is a thin but strong layer, only about 10 microns thick, which was discovered in 2005. The Descemet’s membrane (8B) is a thin layer that is secreted by the endothelium (9), acts as a bed for the endothelial cells to rest on, and is only about 5 to about 10 microns thick. The endothelium (9) is a singular layer of cells and only about 5 microns thick; this layer helps to maintain fluid equilibrium from inside the stroma (7). The main functions of the endothelium (9) are to pump out fluid so that the stroma (7) remains optically clear, and to allow nutrients to enter the cornea (4) from the aqueous humor in the anterior chamber.

[0049] As to particular embodiments, the system can be useful for separating layers of the cornea (4), for example the Descemet’s membrane (8B) and the stroma (7), such as for Deep Anterior Lamellar Keratoplasty (DALK) which is a surgical procedure used to treat corneal diseases, especially those affecting the anterior layers of the cornea (4), specifically the epithelium (5), Bowman’s layer (6), and the stroma (7). A DALK procedure removes only the diseased layers of the cornea (4) in a live patient’s eye and replaces said layers with healthy donor epithelium (5), Bowman’s layer (6), and stroma (7). Correspondingly, the posterior, non-diseased Descemet’s membrane (8B) and endothelium (9) can be preserved. DALK may be preferred over full-thickness corneal transplantation (penetrating keratoplasty) because this procedure leaves the patient's Descemet’s membrane (8B) and endothelium (9) intact, which can reduce the risk of rejection and other complications associated with full-thickness corneal transplants as well as improve the overall outcome of the surgery.

[0050] As to particular embodiments, the system can be useful for separating layers of the cornea (4), for example the Descemet’s membrane (8B) and the stroma (7), such as for Descemet’s Membrane Endothelial Keratoplasty (DMEK), Descemet’s Membrane Anterior Keratoplasty (DMAK), and BrightMEM Anterior Keratoplasty (BMAK).

[0051] As to particular embodiments, the system can be useful for separating layers of the cornea (4), for example the pre-Descemet’s membrane (8 A) and the stroma (7), such as for DALK and Pre-Descemet’s Endothelial Keratoplasty (PDEK).1148P01T

[0052] As to particular embodiments, the system can be useful for separating layers of the cornea (4), for example the stroma (7) and the Bowman’s layer (6), such as for Bowman’s layer transplantation.

[0053] As to particular embodiments, the system can be useful for separating layers of the cornea (4) using hydrodelineation for manual dissection, whereby fluid injection may create space between the cells of the stroma (7) to facilitate dissection.

[0054] As to particular embodiments, the system can be useful for delivery of fluids to specific layers of or locations within the cornea (4), including antibiotic agents, antifungal agents, crosslinking agents, cell therapies, gene therapies, dyes, corneal stromal fillers (such as gels), corneal implants, prophylactic agents, diagnostic agents, therapeutic agents, or the like.

[0055] As to particular embodiments, the system can be useful for separating layers of the cornea, for example the Descemet’s membrane (8B) and the stroma (7), via generation (or formation or creation or production) of a bubble therebetween, whereby the bubble may create a space between the layers, making it easier for the user (such as a surgeon) to visualize, access, and remove the diseased layers of the cornea (4). Additionally, by creating a space between the Descemet’s membrane (8B) and the stroma (7), the risk of damaging the underlying layers can be lessened.

[0056] Notably, whilst bubble generation can significantly aid in surgical procedures, the technique to generate an effective bubble between layers of the cornea (4) may be challenging; in particular, inserting the injector (3) into the correct plane to generate an effective bubble can be difficult. Further, in DALK procedures, there can be a significant risk of perforating the patient’s Descemet’s membrane (8B) when the injector (3) is inserted into the incorrect plane. Beneficially, the present novel system and method effectively address these as well as other challenges, such as by providing relatively standardized devices and methods for optimal positioning of the injector (3) within the cornea (4) for effective bubble generation to separate layers of corneal tissue.

[0057] Now referring primarily to Figures 3A through 4B and 8A through 9B, the present intraocular injection device (1) includes an annular member (10) having an annular first wall1148P01T

[0058] (11) disposed about (such as radially disposed about) or surrounding (such as radially surrounding) or enclosing (such as radially enclosing) an annular member interior space (12) located in the middle of the annular member (10). A first wall bottom end (13) can provide an annular member bottom end (14) as well as the bottom end of the intraocular injection device (1); as a point of reference for the below description, the first wall bottom end (13) may include a first wall bottom surface (15) which can define a generally horizontal reference plane (16) (as shown in Figures 3A and 8A). When the intraocular injection device (1) is in use, the generally horizontal reference plane (16) can dispose in generally parallel relation to the ocular surface and specifically, to a plane tangent to the middle of the portion of the ocular surface over which the intraocular injection device (1) is centered.

[0059] Now referring primarily to Figures 4A and 9A, an annular member central longitudinal axis (17) can extend vertically through the center of the annular member interior space (12), passing through an annular member top end (18) and the annular member bottom end (14). Additionally, the annular member central longitudinal axis (17) can dispose in generally perpendicular relation to the generally horizontal reference plane (16). Conveniently, the annular member interior space (12) can allow a user to view the ocular surface including the cornea (4) firstly to effectively position the intraocular injection device (1) thereon, and secondly during the surgical procedure.

[0060] Dimensionally, the first wall (11) can include a first wall height (19) disposed between a first wall top end (20) and the first wall bottom end (13), whereby the first wall height (19) may be about 5 millimeters (mm) to about 50 mm, depending upon the embodiment. As to particular embodiments, the first wall height (19) can be about 10 mm to about 20 mm. As but one illustrative example, the first wall height (19) can be about 15 mm (such as in Figures 3 A through 4B). As but a second illustrative example, the first wall height (19) can be about 22 mm (such as in Figures 8A through 9B).

[0061] The first wall (11) can include a first wall thickness (21) disposed between a first wall exterior surface (22) and a first wall interior surface (23), whereby the first wall thickness (21) may be generally constant along the first wall height (19) or vary along the first wall height (19), depending upon the embodiment. The first wall thickness (21) can be about 0.5 mm to about 3 mm, depending upon the embodiment. As but one illustrative example, the first wall thickness (21) can be about 1.5 mm and generally constant along the first wall height (19) (such as in1148P01T

[0062] Figures 3A through 4B). As but a second illustrative example, the first wall thickness (21) can vary between about 0.75 mm and about 2.5 mm along the first wall height (19) (such as in Figures 8A through 9B).

[0063] As to particular embodiments, the first wall (11) can but need not necessarily have a tubelike, generally cylindrical shape with a generally circular cross-section. Regarding such embodiments, the first wall (11) can include a first wall outer diameter of about 4 mm to about 20 mm; as but one illustrative example, the first wall outer diameter may be about 13 mm. Also, the first wall (11) can include a first wall inner diameter of about 3.5 mm to about 17.5 mm. As but one illustrative example, the first wall inner diameter can be about 11.5 mm (such as in Figures 3 A through 4B). As but a second illustrative example, the first wall inner diameter can be about 8 mm (such as in Figures 8A through 9B).

[0064] Now referring primarily to Figures 4A, 4B, 9A, and 9B, the annular member (10) can further include an annular second wall (24) disposed in spaced-apart relation to the annular first wall (11) to define an annular chamber (25) therebetween. The second wall (24) can be disposed within the first wall (11) in spaced-apart relation, such as concentrically disposed within the first wall (11) in radially spaced-apart relation; thus, the first wall (11) may be disposed about (or around or radially outward from) the second wall (24) to surround (such as radially surround) or enclose (such as radially enclose) the second wall (24); correspondingly, the first wall (11) can be an outer wall and the second wall (24) can be an inner wall.

[0065] Again referring primarily to Figures 4A, 4B, 9A, and 9B, the second wall (24) can be disposed about (or around or radially outward from) the annular member interior space (12) to surround (such as radially surround) or enclose (such as radially enclose) the annular member interior space (12) located in the middle of the annular member (10), whereby a second wall interior surface (26) may define a generally hollow annular member interior space (12). As to particular embodiments, the second wall (24) can but need not necessarily have a tube-like, generally cylindrical shape with a generally circular cross-section.

[0066] Again referring primarily to Figures 4A, 4B, 9A, and 9B, in particular, a first wall interior surface (23) and a second wall exterior surface (27) can define the chamber (25). As to particular embodiments having a generally cylindrical first wall (11) and second wall (24), the chamber (25) can span 360°.1148P01T

[0067] Now referring primarily to Figure 3B and 3H through 4B, the first wall bottom end (13) can include the first wall bottom surface (15) and likewise, a second wall bottom end (28) may include a second wall bottom surface (29); when the intraocular injection device (1) is in use, both the first wall bottom surface (15) and the second wall bottom surface (29) can contactingly engage with the eye and in particular, with the ocular surface, such as the anterior surface of the eye proximate the cornea (4). As the eye globe is roughly spherical and thus, has a generally convex surface, a second wall height (30), which disposes between a second wall top end (31) and the second wall bottom end (28), can be less than the first wall height (19) to define a generally concave cavity which follows the convex curvature of the eye globe to facilitate effective contacting engagement of the first wall bottom surface (15) and the second wall bottom surface (29) with the ocular surface.

[0068] Further, both the first wall bottom surface (15) and the second wall bottom surface (29) can each include a chamfer (32) which slopes upwardly from the periphery of the annular member (10) toward the center of the annular member (10), whereby the chamfers (32) may also follow the convex curvature of the eye globe to facilitate effective contacting engagement of the first wall bottom surface (15) and the second wall bottom surface (29) with the ocular surface.

[0069] The first wall top end (20) and the second wall top end (31) can be coupled or connected, such as by a top wall extending therebetween, to provide a closed chamber top end (33). Conversely, the chamber (25) can include an open chamber bottom end (34) disposed between the first wall bottom surface (15) and the second wall bottom surface (29). Accordingly, when the intraocular injection device (1) is in use, and the first wall bottom surface (15) and the second wall bottom surface (29) contactingly engage with the ocular surface, the chamber (25) can be communicatively coupled to the ocular surface via the open chamber bottom end (34). Following, the ocular surface can be fluidically coupled to fluid within the chamber (25), for example gas, such that the ocular surface may be subjected or exposed to the pressure within the chamber (25). Said another way, the pressure within the chamber (25) can be applied to the ocular surface.

[0070] Dimensionally, the chamber (25) can have a chamber thickness (35) disposed between the first wall interior surface (23) and the second wall exterior surface (27), whereby the chamber1148P01T

[0071] thickness (35) may be about 0.25 mm to about 2.5 mm, depending upon the embodiment; as but one illustrative example, the chamber thickness (35) can be about 1.6 mm.

[0072] Further, the chamber (25) can have a height dictated, at least in part, by the first wall height (19) and / or the second wall height (30). Regarding the latter, which can be less than the first wall height (19) as detailed above, the second wall height (30) can be about 2 mm to about 50 mm, depending upon the embodiment.

[0073] Now referring primarily to Figures 3A through 4B, as to particular embodiments, the second wall height (30) can be relatively similar to the first wall height (19); thus, the height of the chamber (25) may be relatively similar to the height of the first wall interior surface (23) and the height of the second wall exterior surface (27) such that the chamber (25) can extend upwardly from the open chamber bottom end (34) along a majority of the height of the annular member (10). As to particular embodiments, the second wall height (30) can be about 10 mm to about 20 mm; as but one illustrative example, the second wall height (30) may be about 13.8 mm.

[0074] Now referring primarily to Figures 8A through 9B, as to particular embodiments, the second wall height (30) can be relatively dissimilar to, and in particular shorter than, the first wall height (19); thus, the height of the chamber (25) may be relatively dissimilar to, and in particular shorter than, the height of the first wall (11) and the first wall interior surface (23) such that the chamber (25) can extend upwardly from the open chamber bottom end (34) along only a minority of the height of the annular member (10) proximate the annular member bottom end (14). As to particular embodiments, the second wall height (30) can be about 0.5 mm to about 20 mm; as but one illustrative example, the second wall height (30) may be about 2.3 mm.

[0075] Dimensionally, the second wall (24) can include a second wall thickness (36) disposed between the second wall exterior surface (27) and the second wall interior surface (26), whereby the second wall thickness (36) may be generally constant along the second wall height (30) or vary along the second wall height (30), depending upon the embodiment. The second wall thickness (36) can be about 0.2 mm to about 3 mm, depending upon the embodiment. As but one illustrative example, the second wall thickness (36) can be generally constant along the second wall height (30) and may be about 1 mm (such as in Figures 3A through 4B); regarding such embodiments, the second wall (24) can include a second wall outer diameter of about 2 mm to1148P01T

[0076] about 18 mm; for example, the second wall outer diameter may be about 9 mm. Also, the second wall (24) can include a second wall inner diameter of about 6 mm to about 12 mm; for example, the second wall inner diameter may be about 8 mm. As but a second illustrative example, the second wall thickness (36) can vary along the second wall height (30) (such as in Figures 8A through 9B).

[0077] Now referring primarily to Figure 1, the present system for separating layers of ocular tissue can include a pressure regulator (2) operably coupled to the chamber (25), whereby the pressure regulator (2) may regulate the pressure within the chamber (25). For example, the pressure regulator (2) can be configured as a vacuum generator capable of generating sub-atmospheric pressure within the chamber (25). When the intraocular injection device (1) is in use, and the first wall bottom surface (15) and the second wall bottom surface (29) contactingly engage with the ocular surface, this portion of the ocular surface can be subjected to sub-atmospheric pressure or a vacuum which may apply suction to the ocular surface. Consequently, such a mechanical force can facilitate secure contacting engagement of the intraocular injection device (1) with the eye (for example by “locking” the device to the eye) as well as stabilization and movement minimization of the cornea (4) for the subsequent injection detailed below. Pressures which may be useful to effectively apply suction to the ocular surface can be lesser than atmospheric pressure, such as about -1.5 psi to about -7 psi, depending upon the embodiment; as but one illustrative example, a useful pressure may be about -5 psi. Following use, the pressure within the chamber (25) can be increased to atmospheric pressure or greater to facilitate disengagement of the intraocular injection device (1) from the eye.

[0078] A discrete pressure regulator (2) can be removably coupled or removably connected to the intraocular injection device (1) and in particular, to the annular member (10), via one or more ports (37) passing through the first wall (11) and in fluidic communication with the chamber (25) for pressure regulation thereof. The port (37) can include a port axis (38) extending therethrough, whereby as to particular embodiments, the port axis (38) may be generally parallel to the generally horizontal reference plane (16).

[0079] Now referring primarily to Figures 3 A through 4B, as to particular embodiments, the port (37) can be disposed proximate the first wall top end (20), whereby such a location may facilitate a more even application of sub-atmospheric pressure to the ocular surface relative to a port (37) disposed proximate the first wall bottom end (13).1148P01T

[0080] Now referring primarily to Figures 8A through 9B, as to other particular embodiments, the port (37) can be disposed proximate the first wall bottom end (13).

[0081] As to particular embodiments, the port (37) can be defined by the portion of the first wall (11) through which it passes and by the internal surface of a first elongate member (39), for example a tube-like member, which outwardly extends from the first wall exterior surface (22). As the port axis (38) can be generally parallel to the generally horizontal reference plane (16), the first elongate member (39) may also be generally parallel to the generally horizontal reference plane (16).

[0082] The pressure regulator (2) can have a numerous and wide variety of suitable configurations, depending upon the embodiment. As but one illustrative example, the pressure regulator (2) can include a syringe (40) configured to move fluid between a syringe barrel (41) and the distal end of a conduit (42), whereby the distal end of the conduit (42) may be fluidically coupled to the chamber (25) via the port (37). As to particular embodiments, the diameter of the conduit (42) can be about 0.5 mm to about 10 mm, depending upon the embodiment; as but one illustrative example, the diameter of the conduit (42) may be about 2 mm.

[0083] As would be known to one of ordinary skill in the art, the syringe (40) can include an actuator (43), such as a piston or a plunger, upon which force may be exerted to slidingly move the actuator (43) within the syringe barrel (41) to correspondingly move the fluid between the syringe barrel (41), the conduit (42), and the chamber (25). Again as would be known to one of ordinary skill in the art, a depressed actuator (43) can be pulled to move fluid, such as a gas (for example air), from the chamber (25) into the syringe barrel (41) to generate a vacuum within the chamber (25). The syringe (40) can be manually operated, or it may be partly or completely automated, depending upon the embodiment. Regarding the latter, the syringe (40) can be operably connected to a pump or other machine-powered actuator device, and it may be controlled by a controller containing a processor configured to operate the actuator (43).

[0084] The intraocular injection device (1) can further include a needle guide channel (44) passing (i) through the first wall (11) (as shown in Figures 8A through 9B) or (ii) through the first wall (11) and the second wall (24) (as shown in Figures 3 A through 4B), whereby the needle guide channel (44) may be configured to receive a needle of an injector (3), and guide its needle1148P01T

[0085] tip (45) to a predetermined location within the annular member interior space (12). As to particular embodiments, when the intraocular injection device (1) is in use, the needle guide channel (44) can be configured to guide the needle tip (45) to a predetermined target injection location (IL) within the cornea (4), specifically to a predetermined target injection location (IL) between layers of the cornea (4), and more specifically to a predetermined target injection location (IL) between the Descemet’s membrane (8B) and the stroma (7).

[0086] As to particular embodiments, the needle guide channel (44) and the port (37) can dispose on opposing or diametrically opposing sides of the annular member (11), whereby such disposition may facilitate ease of use of the intraocular injection device (1).

[0087] As to particular embodiments, the needle guide channel (44) can be defined by the internal surface of a second elongate member (46), for example a tube-like member, which passes (i) through the first wall (11) (as shown in Figures 8A through 9B) or (ii) through the first wall (11) and the second wall (24) (as shown in Figures 3 A through 4B). Regarding the latter, the second elongate member (46) can additionally pass through the chamber (25); correspondingly, the needle guide channel (44) may be fluidically isolated from the chamber (25) by the second elongate member (46) such that there is no fluid communication therebetween.

[0088] The needle guide channel (44) can include a needle guide channel length (47) disposed between a needle guide channel entry (48) and a needle guide channel exit (49), whereby a central needle guide channel axis (50) may pass therethrough. The needle guide channel exit (49) can be located proximate the annular member interior space (12) such that the needle tip (45) of a needle received within the needle guide channel (44) may be positioned within the annular member interior space (12).

[0089] The second elongate member (46) and the needle guide channel (44) can outwardly extend from the first wall exterior surface (22) to dispose the channel entry (48) distal from the first wall exterior surface (22). The needle guide channel length (47) can be configured to accommodate a particular needle having a specific needle length, which may be a standard needle length, to position the needle tip (45) (i) at the predetermined location within the annular member interior space (12) and (ii) at the predetermined target injection location (IL) within the cornea (4) when the intraocular injection device (1) is in use. The needle guide channel length1148P01T

[0090] (47) can be about 3 mm to about 50 mm, depending upon the embodiment; as but one illustrative example, the needle guide channel length (47) may be about 19.3 mm, which may accommodate a needle having a needle length of about 1 inch (25.4 mm). To accommodate a needle having a needle length of about % inch to about i inch, the needle guide channel length (47) can be about 4.5 mm to about 6.8 mm. To accommodate a needle having a needle length of about 1*4 inch to about P inch, the needle guide channel length (47) can be about 25.75 mm to about 32 mm.

[0091] Akin to the needle guide channel length (47), the needle guide channel (44) can have a needle guide channel diameter (51) configured to closely accommodate a particular needle having a specific needle diameter, which may be a standard needle diameter, such that radial movement of the needle within the needle guide channel (44) can be minimized to facilitate positioning of the needle tip (45) (i) at the predetermined location within the annular member interior space (12) and (ii) at the predetermined target injection location (IL) within the cornea (4) when the intraocular injection device (1) is in use. The needle guide channel diameter (51) can be about 0.5 mm to about 1.5 mm, depending upon the embodiment; as but one illustrative example, the needle guide channel diameter (51) may be about 0.61 mm, which can accommodate a 26 gauge needle. As to particular embodiments, the needle guide channel diameter (51) can be dimensioned to accommodate a needle in the range of between about 25 gauge to about 30 gauge. As to particular embodiments, the needle guide channel diameter (51) can be dimensioned to accommodate a needle with an outer diameter of about 0.3 mm to about 0.55 mm. As to particular embodiments, the difference between the needle guide channel diameter (51) and the outer diameter of the needle can be not greater than about 0.2 mm or not greater than about 0.15 mm.

[0092] To further facilitate positioning of the needle tip (45) (i) at the predetermined location within the annular member interior space (12) and (ii) at the predetermined target injection location (IL) within the cornea (4) when the intraocular injection device (1) is in use, the second elongate member (46) can include one or more stop elements (52) configured to stop lengthwise travel of the needle through the needle guide channel (44) and correspondingly dictate the injection depth of the needle tip (45). As to particular embodiments, the injection depth of the needle tip (45) can be between about 70% to about 90% of the corneal thickness.

[0093] The stop element (52) can have a numerous and wide variety of suitable configurations, depending upon the embodiment. As but one illustrative example, the stop element (52) can be1148P01T

[0094] configured to contact a hub (53) of the needle to stop lengthwise travel thereof through the needle guide channel (44). As to particular embodiments, the surface of the second elongate member (46) proximate the needle guide channel entry (48) can provide the stop element (52) which may contact a shoulder, edge, or surface of the hub (53) at the juncture of the needle and the hub (53), whereby such contact stops lengthwise travel of the needle through the needle guide channel (44) to position the needle tip (45) (i) at the predetermined location within the annular member interior space (12) and (ii) at the predetermined target injection location (IL) within the cornea (4) when the intraocular injection device (1) is in use.

[0095] Now referring primarily to Figures 4A, 5A, 5B, and 9A, the needle guide channel (44) and the needle guide channel axis (50) can be off-set (such as radially or laterally off-set) from the annular member central longitudinal axis (17) which extends vertically through the center of the annular member interior space (12) and passes through the annular member top end (18) and the annular member bottom end (14). As a result of such off-set positioning, the needle guide channel axis (50) does not intersect with the annular member central longitudinal axis (17); this can be in stark contrast to needle guide axes of known intraocular injection devices which typically pass through the center of the device and thus, intersect with the central longitudinal axis thereof.

[0096] Now referring primarily to Figures 3G, 3H, 8G, and 8H, when viewing the intraocular injection device (1) from the top or bottom, the needle guide channel axis (50) can be non-diametrically disposed within the annular member interior space (12), whereby as used herein, the term “non-diametrically” may mean not along a diameter of a circle resulting from crosssectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26). Conversely, the term “diametrically” can mean along said diameter.

[0097] Again referring primarily to Figures 3G, 3H, 8G, and 8H, said another way, when viewing the intraocular injection device (1) from the top or bottom, the needle guide channel axis (50) can be secantally disposed within the annular member interior space (12) along any secant other than a secant which passes through the center of a circle resulting from crosssectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) and hence, other than a diameter of a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26). As used herein, the term “secant” can mean a line that intersects a circle at two distinct points.1148P01T

[0098] Whereas a diameter of a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) cuts the area of said circle into two equal halves, the present needle guide channel axis (50) can cut said area into two unequal portions, whereby the greater the difference between the two unequal portions, the more peripheral the needle guide channel axis (50) may dispose within the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from crosssectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 40% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 35% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 30% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 25% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 20% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 15% of the area of the circle. As to particular embodiments, the needle guide channel axis (50) can cut through a circle resulting from cross-sectioning the cylinder defined by the first wall interior surface (23) or by the second wall interior surface (26) to provide a portion which comprises not greater than about 10% of the area of the circle.

[0099] Off-setting the needle guide channel axis (50) from the annular member central longitudinal axis (17) results in a peripheral needle guide channel axis (50) which can position the needle tip (45) proximate the peripheral portion (54) of the cornea (4) (or cornea periphery) as opposed to the central portion (55) of the cornea (4) (or cornea center).1148P01T

[0100] As to particular embodiments, the peripheral portion (54) of the cornea (4) can generally include the outer about 85% of the cornea (4) whereas the central portion (55) of the cornea (4) may generally include the inner about 15% of the cornea (4).

[0101] As to particular embodiments, the peripheral portion (54) of the cornea (4) can generally include the outer about 75% of the cornea (4) whereas the central portion (55) of the cornea (4) may generally include the inner about 25% of the cornea (4).

[0102] As to particular embodiments, the peripheral portion (54) of the cornea (4) can generally include the outer about 66% of the cornea (4) whereas the central portion (55) of the cornea (4) may generally include the inner about 33% of the cornea (4), as shown in Figure 7A.

[0103] As to particular embodiments, the peripheral portion (54) of the cornea (4) can generally include the outer about 50% of the cornea (4) whereas the central portion (55) of the cornea (4) may generally include the inner about 50% of the cornea (4).

[0104] As to particular embodiments, the peripheral portion (54) of the cornea (4) can generally include the outer about 33% of the cornea (4) whereas the central portion (55) of the cornea (4) may generally include the inner about 66% of the cornea (4), as shown in Figure 7.

[0105] Of note, the thickness of the peripheral portion (54) of the cornea (4) can have less interpatient variability than the central portion (55) of the cornea (4). Following, it can be advantageous to target the peripheral portion (55) of the cornea (4) when employing a relatively standardized intraocular injection device (1) to achieve an injection depth which effectively positions a needle tip (45) between the Descemet’s membrane (8B) and the stroma (7) in a wide variety of patients.

[0106] Now referring primarily to Figures 4A and 9A, the needle guide channel axis (50) can be angled in relation to the generally horizontal reference plane (16) such that the needle guide channel axis (50) downwardly extends from the needle guide channel entry (48) to the needle guide channel exit (49), thus disposing the needle guide channel exit (49) below the needle guide channel entry (48). The needle guide channel axis (50) can be disposed at an angle (56) of less than about 90° relative to the generally horizontal reference plane (16) which may be considered1148P01T

[0107] to dispose at an angle of 0°. Depending upon the embodiment, the needle guide channel axis (50) can be disposed at an angle (56) of about 15° to about 30° relative to the generally horizontal reference plane (16); as but one illustrative example, the needle guide channel axis (50) may be disposed at an angle (56) of about 20° relative to the generally horizontal reference plane (16). Of course, the angle (56) of the needle guide channel axis (50) relative to the generally horizontal reference plane (16) directly dictates the angle at which the needle tip (45) enters the cornea (4) for an injection therein. As to particular embodiments, the angle (56) can be generally tangential to the peripheral cornea (4). As to particular embodiments, the angle (56) can be generally tangential to the Descemet’s membrane (8B).

[0108] For said injection, the present system for separating layers of ocular tissue can include a discrete injector (3) which includes a needle comprising a relatively long and slender needle shaft (57) (typically but not necessarily made from stainless steel) that may be beveled at one end to form a point. The bevel can be the ground surface of the needle tip (45) or cannula, in practice the cutting edge of the needle. The hollow bore of the needle shaft (57) is termed the needle lumen. Opposite the needle tip (45) can be the hub (53) which attaches the needle shaft (57) to a syringe (40).

[0109] The needle can also include a connector for attaching to the syringe barrel (41) of a cooperating syringe (40) by means of a press-fit or twist-on fitting, such as a Luer taper type of connector, for example locking (“Luer-Lok”) fittings that may be securely joined by means of a tabbed hub on the female fitting which screws into threads in a sleeve on the male fitting, or slipping (“Luer-Slip”) fittings that simply conform to Luer taper dimensions and can be pressed together and held by friction.

[0110] The needle size can be designated by needle length and needle gauge. The length of a needle can be measured from the juncture of the hub (53) and the needle shaft (57) to the needle tip (45). The gauge of a needle can be used to designate the outer radius of the needle. As to particular embodiments, needles gauges which may be useful with the present intraocular injection device (1) can include about 25 gauge to about 30 gauge.

[0111] The needle tip (45) can have a variety of configurations, depending upon the embodiment, including pencil point, lancet, asymmetrical, long bevel, regular bevel, short bevel, 5-bevel, blunt tip, or the like.1148P01T

[0112] As to particular embodiments, an injector (3) which may be useful with the present intraocular injection device (1) can be configured as a hypodermic needle.

[0113] The syringe (40) used in conjunction with the needle can be structurally the same as or similar to the syringe (40) detailed above, and may include an actuator (43) upon which force can be exerted for sliding movement thereof within the syringe barrel (41) to correspondingly move fluid from the syringe barrel (41) through the needle lumen to the needle tip (45) for injection into the cornea (4). As to particular embodiments, syringe volumes which may be useful with the present intraocular injection device (1) can include about 300 microliters (pL) to about 5 milliliters (mL).

[0114] The intraocular injection device (1) can further include one or more handles (58) coupled to the annular member (10) and outwardly extending therefrom, whereby the handle (58) may provide a secure way to hold and manipulate the intraocular injection device (1). As to particular embodiments, the handle (58) can be coupled to the annular member (10) proximate the annular member top end (18). As to particular embodiments, the handle (58) can be offset from the needle guide channel (44) and the port (37), which may facilitate ease of use. The handle (58) can have any suitable size and any suitable shape, such as cylindrical, cuboidal, trapezoidal, etc., depending upon the embodiment. As to particular embodiments, a pair of handles (58) can be coupled to the annular member top end (18) in opposed relation to outwardly extend from the annular member (10) in opposite directions.

[0115] The intraocular injection device (1) or components of the intraocular injection device (1) can be produced from any of a numerous and wide variety of suitable processes depending upon the application, such as press molding, injection molding, fabrication, machining, printing, three-dimensional printing, or the like, or combinations thereof. Also, the intraocular injection device (1) or components of the intraocular injection device (1) can be made from any of a numerous and wide variety of suitable materials depending upon the application, for example semi-rigid or rigid materials, such as plastics or metals. As to particular embodiments, the material can be transparent or translucent, which may allow visualization therethrough.

[0116] As to particular embodiments, the intraocular injection device (1) can be provided as an integral, one-piece construct comprising, consisting essentially of, or consisting of the annular1148P01T

[0117] member (10), the first elongate member (39), its associated port (37), the second elongate member (46), its associated needle guide channel (44), and the handle (58).

[0118] As to other particular embodiments, the intraocular injection device (1) can be provided as a plurality of components for assembly into an embodiment of the intraocular injection device (1).

[0119] For the present novel method of separating layers of ocular tissue, the fluid injected into the cornea (4) via the injector (3) can generate a bubble therein, whereby the bubble may create a space between the layers of corneal tissue. As to particular embodiments, the injected fluid can generate a bubble between the Descemet’s membrane (8B) and the stroma (7) which may aid a user in removing the epithelium (5), Bowman’s layer (6), and the stroma (7) (one or more of which may be diseased) while preserving the non-diseased Descemet’s membrane (8B) and endothelium (9). As to particular embodiments, the injected fluid can generate a bubble between the pre-Descemet’s membrane (8 A) and the stroma (7) or between the pre-Descemet’s membrane (8 A) and the Descemet’s membrane (8B).

[0120] As to particular embodiments, the fluid injected into the cornea (4) for bubble generation can comprise, consist essentially of, or consist of gas, such as air, which correspondingly may generate an air bubble between the Descemet’s membrane (8B) and the stroma (7). Such an air bubble can typically be translucent or opaque, which may preclude effective visualization of the cornea (4). As to other particular embodiments, the gas injected into the cornea (4) for bubble generation can comprise sulfur hexafluoride (SFe), perfluoroethane (C2F6), perfluoropropane (CsFs), or the like.

[0121] As to other particular embodiments, the fluid injected into the cornea (4) for bubble generation can comprise, consist essentially of, or consist of liquid which correspondingly may generate a liquid bubble, whereby such a fluid injection technique may be referred to as hydrodissection. As opposed to an air bubble, a liquid bubble generated between the Descemet’s membrane (8B) and the stroma (7) can be translucent or transparent, which may allow effective visualization of the cornea (4).

[0122] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can have a sufficient viscosity to facilitate mechanical separation of layers of corneal1148P01T

[0123] tissue. As to particular embodiments, the viscosity of the fluid can be about 0.7 centipoise (cP) to about 4,000,000 cP at about 37° Celsius (C). As to particular embodiments, the viscosity of the fluid can be about 0.7 cP to about 25,000 cP at about 37° C. As to particular embodiments, the viscosity of the fluid can be about 0.7 cP to about 100 cP at about 37° C. Of note, fluids with a relatively lower viscosity can penetrate the small spaces between the lamellae of the cornea and correspondingly, may facilitate a smooth hydrodissection. Conversely, fluids with a relatively higher viscosity can cause excessive pressure and resultant tissue damage.

[0124] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can have a sufficient osmolarity (or osmotic concentration) to facilitate mechanical separation of layers of corneal tissue, whereby hypotonic, isotonic, or hypertonic fluids may be useful, depending upon the embodiment. As to particular embodiments, the osmolarity of the fluid can be about 200 milliosmoles per kilogram (mOsm / kg) to about 400 mOsm / kg. As to particular embodiments, the osmolarity of the fluid can be about 250 mOsm / kg to about 400 mOsm / kg. As to particular embodiments, a fluid which has an osmolarity that is similar to or the same as that of aqueous humor can be useful and may minimize or prevent osmotic imbalances which can cause detrimental corneal dehydration or swelling.

[0125] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can have a sufficient pH to facilitate mechanical separation of layers of corneal tissue. As to particular embodiments, the pH of the fluid can be about 6.5 to about 8.5. As to particular embodiments, the pH of the fluid can be about 7.0 to about 7.9. As to particular embodiments, a fluid which has a pH that is similar to or the same as a physiological pH of about 7.4 can be useful and may minimize tissue irritation, damage, and cytotoxicity. As to particular embodiments, a fluid which has a pH that is substantially neutral or neutral can be useful and may preserve corneal cell function and viability.

[0126] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can have a sufficient surface tension to facilitate mechanical separation of layers of corneal tissue. As to particular embodiments, the surface tension of the fluid can be about 20 milliNewtons per meter (mN / m) to about 80 mN / m. As to particular embodiments, the surface tension of the fluid can be about 40 mN / m to about 75 mN / m. Of note, fluids with a surface tension that is lower than that of water can penetrate the small spaces between the lamellae of the cornea and correspondingly, may facilitate a smooth hydrodissection.1148P01T

[0127] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can have a sufficient working temperature to facilitate mechanical separation of layers of corneal tissue. As to particular embodiments, the working temperature of the fluid can be about 20° C to about 40° C. As to particular embodiments, the working temperature of the fluid can be about 31° C to about 37° C. As to particular embodiments, a fluid which has a working temperature that is similar to or the same as body temperature can be useful for maintaining cellular metabolism and may reduce patient discomfort and minimize or prevent thermal shock or cellular impairment.

[0128] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can be optically clear and / or have a refractive index that is similar to or the same as that of the cornea, which may enable the user (such as a surgeon) to visualize the layers of corneal tissue and / or monitor the hydrodissection in real-time. As to particular embodiments, the optically clear fluid can be colored to facilitate effective visualization, reproducibility, and ease of the hydrodissection; as illustrative examples, the optically clear fluid can be colored purple, blue, green, cyan, orange, or the like.

[0129] As a first illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise a balanced salt solution. As to particular embodiments, the balanced salt solution can have one or more of (i) a viscosity of about 0.7 cP to about 0.9 cP at about 37° C, (ii) an osmolarity of about 300 mOsm / kg to about 305 mOsm / kg, (iii) a pH of about 7.4, and (iv) a surface tension of about 55 mN / m to about 60 mN / m. As to particular embodiments, the balanced salt solution can comprise one or more of (i) sodium chloride (NaCl), (ii) potassium chloride (KC1), (iii) calcium chloride dihydrate (CaCh 2H2O), (iv) magnesium chloride hexahydrate (MgCh 6H2O), (v) sodium acetate trihydrate (C2HsNaO2 3H2O), and (vi) sodium citrate dihydrate (CeHsNasO? 2H2O). As to particular embodiments, the balanced salt solution can comprise Balanced Salt Solution (BSS).

[0130] As to particular embodiments, the balanced salt solution can additionally comprise one or more of (i) glucose, (ii) glutathione disulfide, and (iii) sodium bicarbonate (NaHCCh). As to particular embodiments, the balanced salt solution can comprise Balanced Salt Solution Plus (BSS Plus).1148P01T

[0131] As a second illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise a viscoelastic fluid. As to particular embodiments, the viscoelastic fluid can comprise sodium hyaluronate and have one or more of (i) a viscosity of about 400,000 cP at about 37° C, (ii) an osmolarity of about 300 mOsm / kg, (iii) a pH of about 7.0 to about 7.5, and (iv) a surface tension which is less than that of water; as to particular embodiments, the viscoelastic fluid can comprise an ophthalmic viscosurgical device (OVD) such as HEALON® or HEALON® PRO, both of which are available from Johnson & Johnson. As to particular embodiments, the viscoelastic fluid can comprise sodium hyaluronate and have one or more of (i) a viscosity of about 2,000,000 cP at about 37° C, (ii) an osmolarity of about 300 mOsm / kg, (iii) a pH of about 7.0 to about 7.5, and (iv) a surface tension which is less than that of water; as to particular embodiments, the viscoelastic fluid can comprise a OVD such as HEALON GV® or HEALON GV® PRO, both of which are available from Johnson & Johnson.

[0132] As to other particular embodiments, the viscoelastic fluid can comprise hydroxypropyl methylcellulose and have one or more of (i) a viscosity of about 4,000 cP at about 37° C, (ii) an osmolarity of about 300 mOsm / kg, (iii) a pH of about 7.2 to about 7.4, and (iv) a surface tension which is less than that of water; as to particular embodiments, the viscoelastic fluid can comprise (i) OCUCOAT® Dispersive Viscoelastic which is available from Bausch + Lomb or (ii) CELLUGEL® OVD which is available from Alcon.

[0133] As a third illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise saline. As to particular embodiments, the saline can include about 0.9% sodium chloride (NaCl) and have one or more of (i) a viscosity of about 0.7 cP to about 0.9 cP at about 37° C, (ii) an osmolarity of about 308 mOsm / kg, (iii) a pH of about 5.5, and (iv) a surface tension of about 72 mN / m.

[0134] As a fourth illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise Ringer's lactate solution. As to particular embodiments, the Ringer's lactate solution can have one or more of (i) a viscosity of about 0.7 cP to about 0.9 cP at about 37° C, (ii) an osmolarity of about 273 mOsm / kg, (iii) a pH of about 6.5, and (iv) a surface tension of about 65 mN / m. As to particular embodiments, the Ringer's lactate solution can comprise one or more of (i) sodium chloride (NaCl), (ii) potassium chloride (KC1), (iii) calcium chloride (CaCL), and (iv) sodium lactate (NaCsHsCh).1148P01T

[0135] As a fifth illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise a perfluorocarbon liquid, such as perfluorodecalin, perfluorobutylpentene, perfluoro-n-octane, or perfluorohexyloctane.

[0136] As a sixth illustrative example, a liquid which may be useful with the present system and method for separating layers of ocular tissue can comprise a corneal storage medium, such as Optisol-GS, Comisol, Life 4°C, Eusol-C, or McCarey-Kaufman medium. These mediums can have a viscosity of about 1.9 cP to about 9.0 cP at about 37° C, an osmolarity of about 255 mOsm / kg to about 390 mOsm / kg, and a pH of about 7.0 to about 7.5.

[0137] As to particular embodiments, solutions including dyes may be useful with the present system and method for separating layers of ocular tissue, such as trypan blue (for example VISIONBLUE® or MEMBRANEBLUE®, both available from DORC), indocyanine green, brilliant blue G, fluorescein sodium, patent blue V, rose bengal, or lissamine green.

[0138] As to particular embodiments, antibacterial solutions and / or antifungal solutions may be useful with the present system and method for separating layers of ocular tissue, such as neomycin, fluoroquinolones, chlorhexidine, amphotericin B, natamycin, or voriconazole.

[0139] As to particular embodiments, for effective hydrodissection and / or bubble generation, the fluid can be one or more of biocompatible, non-toxic, non-immunogenic, preservative-free, pyrogen-free, and / or sterile. Additionally, the fluid should not cause an adverse reaction(s), such as inflammation.

[0140] As to particular embodiments, for effective hydrodissection and / or bubble generation, the amount of fluid injected into the cornea (4) can be about 50 pL to about 250 pL. As to particular embodiments, the amount of fluid injected into the cornea (4) can be about 100 pL to about 200 pL.

[0141] As to particular embodiments, for effective hydrodissection and / or bubble generation, the rate of the fluid injection into the cornea (4) can be relatively slow to facilitate a gradual increase in intrastromal pressure and preclude perforation. As to particular embodiments, the fluid can be injected into the cornea (4) over a period of time which can range from about 01148P01T

[0142] seconds to about 60 seconds. As to particular embodiments, the fluid can be injected into the cornea (4) over a period of time which can range from about 2 seconds to about 20 seconds.

[0143] Now referring primarily to Figures 10A and 11 A, as to particular embodiments, a type 1 bubble, which can form in the center of the cornea (4) (such as the central about 6 mm to about 7.5 mm of the cornea (4)), may be useful for separating the stroma (7) and the pre-Descemet’s membrane (8A). Figure 12 shows a type 1 bubble post procedure using the intraocular injection device (1).

[0144] Now referring primarily to Figures 10B and 1 IB, as to particular embodiments, a type 2 bubble, which can form in the periphery of the cornea (4), may be useful for separating the pre-Descemet’s membrane (8 A) and the Descemet’s membrane (8B).

[0145] Now referring primarily to Figure 10C, as to particular embodiments, a type 3 bubble may not be optimal for separating (i) the stroma (7) and the pre-Descemet’s membrane (8 A) or (ii) the pre-Descemet’s membrane (8 A) and the Descemet’s membrane (8B).

[0146] Now regarding methodology, the present novel method of separating layers of ocular tissue can include positioning the intraocular injection device (1) on the ocular surface to dispose the cornea (4) within the annular member interior space (12), engaging the intraocular injection device (1) with the ocular surface by applying suction to the chamber (25) via a pressure regulator (2), guiding the needle tip (45) of an injector (3) through an off-set needle guide channel (44) to a predetermined target injection location (IL) within a peripheral portion (54) of the cornea (4), and injecting fluid at the predetermined target injection location (IL) via the injector (3) to generate a bubble.

[0147] As to particular embodiments, the predetermined target injection location (IL) within the peripheral portion (54) of the cornea (4) can be between the Descemet’s membrane (8B) and the stroma (7); correspondingly, a bubble can be generated therebetween to assist with separation thereof.

[0148] Notably, for effective positioning of the needle tip (45) at the predetermined target injection location (IL) within the peripheral portion (54) of the cornea (4), the bevel of the needle1148P01T

[0149] tip (45) can be disposed downwardly or towards the Descemet’s membrane (8B) prior to injection.

[0150] As to particular embodiments, if an effective bubble is not generated, the intraocular ocular injection device (1) can be repositioned on the ocular surface and the procedure can be repeated.

[0151] As a result of the needle guide channel (44) and the needle guide channel axis (50) being off-set from the annular member central longitudinal axis (17), the needle tip (45) of a needle received within the needle guide channel (44) can enter the peripheral portion (54) of the cornea (4) (as opposed to the central portion (55) of the cornea (4)). Also as a result of the needle guide channel (44) and the needle guide channel axis (50) being off-set from the annular member central longitudinal axis (17), the needle tip (45) can further travel through the peripheral portion (54) of the cornea (4) to reach a predetermined target injection location (IL) also within the peripheral portion (54) of the cornea (4) (as shown in Figure 7B). Such a cornea periphery entry location (EL) and a cornea periphery target injection location (IL) can be in contrast to (i) a cornea center entry location (EL) and a cornea periphery target injection location (IL) (as shown in Figure 7C) and (ii) a cornea periphery entry location (EL) and a cornea center target injection location (IL) (as shown in Figure 7D). Figure 13A is a microscopic view of a needle tip (45) being inserted into a cornea (4) via the intraocular injection device (1).

[0152] In addition, as a result of the needle guide channel (44) and the needle guide channel axis (50) being off-set from the annular member central longitudinal axis (17), the likelihood of locating the needle tip (45) in the peripheral portion (54) of the cornea (4) and correspondingly reaching a cornea periphery target injection location (IL) can be increased. Consequently, the likelihood of generating a type 2 bubble can be increased.

[0153] The present method of separating layers of ocular tissue can further include monitoring the bubble generation. Indicators of effective bubble generation can include (i) the appearance of a central, dome-shaped elevation, (ii) a clear demarcation between separated layers, and (iii) the movement of an anterior chamber air bubble to the periphery. Conversely, indicators of a complication(s) with effective bubble generation can include the sudden loss of resistance (which may indicate perforation of the Descemet’s membrane). The absence of bubble formation1148P01T

[0154] can indicate failure to reach the predetermined target injection location (IL) due to incorrect placement of the needle tip (45).

[0155] As to particular embodiments, after the bubble is generated, the method can further include trephination of the cornea (4), dissection and removal of the anterior stroma (7), paracentesis into the bubble, and removal of the remaining stroma (7) by elongating the paracentesis into an X shape and cutting, such as with scissors.

[0156] As to particular embodiments, the present method of separating layers of ocular tissue can further include mechanically stabilizing the intraocular injection device (1) using a structure within the eye (E) or a device which may be stably coupled to the eye (E), such as a speculum. Correspondingly, as to particular embodiments, a connector (for example but not limited to a clip, a pressure fit element, or the like) can be coupled to the intraocular injection device (1), whereby the connector may be configured to additionally couple to a speculum to connect the intraocular injection device (1) thereto.

[0157] As to particular embodiments, the present method of separating layers of ocular tissue can further include assessing the thickness and / or curvature of the cornea (4) prior to use of the intraocular injection device (1) to facilitate optimal placement of the annular member (10). As but one illustrative example, an optical coherence topography (OCT) device can be used to determine the thickness of the cornea (4). Such a determination can be useful for positioning the annular member (10) and correspondingly the second elongate member (46) such that the predetermined target injection location (IL) will dispose proximate a peripheral portion (54) of the cornea (4) which may be sufficiently thick to receive the needle tip (45) (as shown in Figure 13B); for example, with about 2.18 millimeters of the needle tip (45) inserted, the distance between (i) the epithelium (5) and (ii) the Descemet’s membrane (8B) and the endothelium (9) is about 651 microns, the distance between the epithelium (5) and the needle tip (45) is about 542 microns, and the distance between the needle tip (45) and the Descemet’s membrane (8B) and endothelium (9) is about 79 microns.

[0158] As can be easily understood from the foregoing, the basic concepts of the present invention may be embodied in a variety of ways. The invention involves numerous and varied embodiments of a system and method for separating layers of ocular tissue.1148P01T

[0159] As such, the particular embodiments or elements of the invention disclosed by the description or shown in the figures or tables accompanying this application are not intended to be limiting, but rather exemplary of the numerous and varied embodiments generically encompassed by the invention or equivalents encompassed with respect to any particular element thereof. In addition, the specific description of a single embodiment or element of the invention may not explicitly describe all embodiments or elements possible; many alternatives are implicitly disclosed by the description and figures.

[0160] It should be understood that each element of an apparatus or each step of a method may be described by an apparatus term or method term. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. As but one example, it should be understood that all steps of a method may be disclosed as an action, a means for taking that action, or as an element which causes that action. Similarly, each element of an apparatus may be disclosed as the physical element or the action which that physical element facilitates. As but one example, the disclosure of an “injector” should be understood to encompass disclosure of the act of “injecting” — whether explicitly discussed or not — and, conversely, were there effectively disclosure of the act of “injecting,” such a disclosure should be understood to encompass disclosure of a “injector” and even a “means for injecting.” Such alternative terms for each element or step are to be understood to be explicitly included in the description.

[0161] In addition, as to each term used it should be understood that unless its utilization in this application is inconsistent with such interpretation, common dictionary definitions should be understood to be included in the description for each term as contained in the Random House Webster’s Unabridged Dictionary, second edition, each definition hereby incorporated by reference.

[0162] All numeric values herein are assumed to be modified by the term “about”, whether or not explicitly indicated. For the purposes of the present invention, ranges may be expressed as from “about” one particular value to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value to the other particular value. The recitation of numerical ranges by endpoints includes all the numeric values subsumed within that range. A numerical range of one to five includes for example the numeric values 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, and so forth. It will be further understood that the endpoints of each of1148P01T

[0163] the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. When a value is expressed as an approximation by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” generally refers to a range of numeric values that one of skill in the art would consider equivalent to the recited numeric value or having the same function or result. Similarly, the antecedent “generally” means largely, but not wholly, the same form, manner or degree and the particular element will have a range of configurations as a person of ordinary skill in the art would consider as having the same function or result. When a particular element is expressed as an approximation by use of the antecedent “generally,” it will be understood that the particular element forms another embodiment.

[0164] Moreover, for the purposes of the present invention, the term “a” or “an” entity refers to one or more of that entity unless otherwise limited. As such, the terms “a” or “an”, “one or more” and “at least one” can be used interchangeably herein.

[0165] Thus, the applicant(s) should be understood to claim at least: i) each of the systems and methods for separating layers of ocular tissue herein disclosed and described, ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative embodiments which accomplish each of the functions shown, disclosed, or described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, ix) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, x) the various combinations and permutations of each of the previous elements disclosed.

[0166] The background section of this patent application, if any, provides a statement of the field of endeavor to which the invention pertains. This section may also incorporate or contain paraphrasing of certain United States patents, patent applications, publications, or subject matter of the claimed invention useful in relating information, problems, or concerns about the state of technology to which the invention is drawn toward. It is not intended that any United States patent, patent application, publication, statement or other information cited or incorporated1148P01T

[0167] herein be interpreted, construed or deemed to be admitted as prior art with respect to the invention.

[0168] The claims set forth in this specification, if any, are hereby incorporated by reference as part of this description of the invention, and the applicant expressly reserves the right to use all of or a portion of such incorporated content of such claims as additional description to support any of or all of the claims or any element or component thereof, and the applicant further expressly reserves the right to move any portion of or all of the incorporated content of such claims or any element or component thereof from the description into the claims or vice-versa as necessary to define the matter for which protection is sought by this application or by any subsequent application or continuation, division, or continuation-in-part application thereof, or to obtain any benefit of, reduction in fees pursuant to, or to comply with the patent laws, rules, or regulations of any country or treaty, and such content incorporated by reference shall survive during the entire pendency of this application including any subsequent continuation, division, or continuation-in-part application thereof or any reissue or extension thereon.

[0169] Additionally, the claims set forth in this specification, if any, are further intended to describe the metes and bounds of a limited number of the preferred embodiments of the invention and are not to be construed as the broadest embodiment of the invention or a complete listing of embodiments of the invention that may be claimed. The applicant does not waive any right to develop further claims based upon the description set forth above as a part of any continuation, division, or continuation-in-part, or similar application.

Claims

1148P01TIV. CLAIMS1. A system for separating layers of ocular tissue, comprising:an intraocular injection device comprising:an annular member comprising an annular first wall; anda needle guide channel extending through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit;wherein said needle guide channel axis is off-set from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis.

2. The system of claim 1, said first wall disposed about an annular member interior space.

3. The system of claim 2, wherein said annular member central longitudinal axis vertically extends through the center of said annular member interior space.

4. The system of claim 1, said first wall comprising a tube-like, generally cylindrical shape with a generally circular cross-section.

5. The system of claim 1, further comprising an annular second wall disposed in spacedapart relation to said first wall to define a chamber therebetween.

6. The system of claim 5, said second wall disposed within said first wall.

7. The system of claim 5, said second wall concentrically disposed within said first wall.

8. The system of claim 5, said first wall disposed about said second wall.

9. The system of claim 5, said second wall disposed about an annular member interior space.

10. The system of claim 9, wherein a second wall interior surface defines said annular member interior space.1148P01T11. The system of claim 5, said second wall comprising a tube-like, generally cylindrical shape with a generally circular cross-section.

12. The system of claim 5, wherein a first wall interior surface and a second wall exterior surface define said chamber.

13. The system of claim 5, wherein said chamber spans 360°.

14. The system of claim 5, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an eye when said intraocular injection device is in use.

15. The system of claim 5, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an ocular surface of an eye when said intraocular injection device is in use.

16. The system of claim 5, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an anterior surface of an eye proximate a cornea when said intraocular injection device is in use.

17. The system of claim 5, wherein a second wall height which disposes between a second wall top end and a second wall bottom end is lesser than a first wall height which disposes between a first wall top end and a first wall bottom end.

18. The system of claim 5, wherein a first wall bottom surface and a second wall bottom surface each comprise a chamfer which slopes upwardly from the periphery of said annular member toward the center of said annular member.

19. The system of claim 5, wherein said chamber comprises a closed chamber top end and an opposing open chamber bottom end.

20. The system of claim 19, wherein said chamber is communicatively coupled to an ocular surface of an eye via said open chamber bottom end when said intraocular injection device is in use.1148P01T21. The system of claim 20, wherein said ocular surface is fluidically coupled to fluid within said chamber when said intraocular injection device is in use.

22. The system of claim 21, wherein said ocular surface is subjected to the pressure within said chamber when said intraocular injection device is in use.

23. The system of claim 5, further comprising a pressure regulator couplable to said chamber to regulate the pressure therein.

24. The system of claim 23, said pressure regulator configured as a vacuum generator capable of generating sub-atmospheric pressure within said chamber.

25. The system of claim 24, wherein said vacuum generator applies suction to an ocular surface of an eye when said intraocular injection device is in use.

26. The system of claim 23, wherein said pressure regulator couples to said chamber via a port which passes through said first wall.

27. The system of claim 26, wherein said port disposes proximate a first wall top end.

28. The system of claim 23, said pressure regulator configured as a syringe.

29. The system of claim 5, wherein said needle guide channel extends through said second wall.

30. The system of claim 1, said needle guide channel configured to receive a needle of an injector.

31. The system of claim 30, said needle guide channel configured to guide a needle tip of said needle to a predetermined location within an annular member interior space.1148P01T32. The system of claim 30, said needle guide channel configured to guide a needle tip of said needle to a predetermined target injection location within a cornea when said intraocular injection device is in use.

33. The system of claim 30, said needle guide channel configured to guide a needle tip of said needle to a predetermined target injection location between layers of a cornea when said intraocular injection device is in use.

34. The system of claim 30, said needle guide channel comprising a needle guide channel length configured to accommodate a particular said needle having a specific needle length.

35. The system of claim 30, said needle guide channel comprising a needle guide channel diameter configured to accommodate a particular said needle having a specific needle diameter.

36. The system of claim 30, further comprising a stop element configured to stop lengthwise travel of said needle through said needle guide channel.

37. The system of claim 36, said stop element configured to contact a hub of said needle to stop said lengthwise travel of said needle through said needle guide channel.

38. The system of claim 1, said needle guide channel axis non-diametrically disposed within an annular member interior space.

39. The system of claim 1, wherein off-setting said needle guide channel axis from said annular member central longitudinal axis positions a needle tip of a needle received within said needle guide channel proximate a peripheral portion of a cornea when said intraocular injection device is in use.

40. The system of claim 1, wherein said needle guide channel axis downwardly extends from said needle guide channel entry to said needle guide channel exit.

41. The system of claim 1, further comprising an injector couplable to said needle guide channel, said injector configured to inject a fluid.1148P01T42. The system of claim 41, wherein said injector comprises a needle.

43. The system of claim 42, further comprising a syringe couplable to said needle.

44. The system of claim 1, further comprising a handle outwardly extending from said annular member.

45. A system for separating layers of ocular tissue, consisting essentially of:an annular member comprising an annular first wall and an annular second wall disposed in spaced-apart relation to define a chamber therebetween;wherein said chamber comprises a closed chamber top end and an opposing open chamber bottom end;a needle guide channel extending through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit;wherein said needle guide channel axis is off-set from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis;a pressure regulator couplable to said chamber to regulate the pressure therein; and an injector couplable to said needle guide channel, said injector configured to inject a fluid.

46. A system for separating layers of ocular tissue, consisting of:an annular member comprising an annular first wall and an annular second wall disposed in spaced-apart relation to define a chamber therebetween;wherein said chamber comprises a closed chamber top end and an opposing open chamber bottom end;a needle guide channel extending through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit;wherein said needle guide channel axis is off-set from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis;a pressure regulator couplable to said chamber to regulate the pressure therein; and1148P01Tan injector couplable to said needle guide channel, said injector configured to inject a fluid.

47. A system for separating layers of ocular tissue, comprising:an annular member comprising an annular first wall and an annular second wall disposed in spaced-apart relation to define a chamber therebetween;wherein said chamber comprises a closed chamber top end and an opposing open chamber bottom end;a needle guide channel extending through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit;wherein said needle guide channel axis is off-set from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis;a pressure regulator couplable to said chamber to regulate the pressure therein; and an injector couplable to said needle guide channel, said injector configured to inject a fluid.

48. A method of making a system for separating layers of ocular tissue, comprising:providing an intraocular injection device by:providing an annular member comprising an annular first wall;extending a needle guide channel through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit; andoff-setting said needle guide channel axis from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis.

49. The method of claim 48, further comprising disposing said first wall about an annular member interior space.

50. The method of claim 49, wherein said annular member central longitudinal axis vertically extends through the center of said annular member interior space.1148P01T51. The method of claim 48, further comprising configuring said first wall to have a tubelike, generally cylindrical shape with a generally circular cross-section.

52. The method of claim 48, further comprising disposing an annular second wall in spacedapart relation to said first wall to define a chamber therebetween.

53. The method of claim 52, further comprising disposing said second wall within said first wall.

54. The method of claim 52, further comprising concentrically disposing said second wall within said first wall.

55. The method of claim 52, further comprising disposing said first wall about said second wall.

56. The method of claim 52, further comprising disposing said second wall about an annular member interior space.

57. The method of claim 56, wherein a second wall interior surface defines said annular member interior space.

58. The method of claim 52, further comprising configuring said second wall to have a tubelike, generally cylindrical shape with a generally circular cross-section.

59. The method of claim 52, wherein a first wall interior surface and a second wall exterior surface define said chamber.

60. The method of claim 52, wherein said chamber spans 360°.

61. The method of claim 52, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an eye when said intraocular injection device is in use.1148P01T62. The method of claim 52, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an ocular surface of an eye when said intraocular injection device is in use.

63. The method of claim 52, wherein a first wall bottom surface and a second wall bottom surface contactingly engage with an anterior surface of an eye proximate a cornea when said intraocular injection device is in use.

64. The method of claim 52, further comprising configuring a second wall height which disposes between a second wall top end and a second wall bottom end to be lesser than a first wall height which disposes between a first wall top end and a first wall bottom end.

65. The method of claim 52, further comprising configuring a first wall bottom surface and a second wall bottom surface to each comprise a chamfer which slopes upwardly from the periphery of said annular member toward the center of said annular member.

66. The method of claim 52, further comprising configuring said chamber to have a closed chamber top end and an opposing open chamber bottom end.

67. The method of claim 66, wherein said chamber is communicatively coupled to an ocular surface of an eye via said open chamber bottom end when said intraocular injection device is in use.

68. The method of claim 67, wherein said ocular surface is fluidically coupled to fluid within said chamber when said intraocular injection device is in use.

69. The method of claim 68, wherein said ocular surface is subjected to the pressure within said chamber when said intraocular injection device is in use.

70. The method of claim 52, further comprising providing a pressure regulator couplable to said chamber to regulate the pressure therein.

71. The method of claim 70, said pressure regulator configured as a vacuum generator capable of generating sub-atmospheric pressure within said chamber.1148P01T72. The method of claim 71, wherein said vacuum generator applies suction to an ocular surface of an eye when said intraocular injection device is in use.

73. The method of claim 70, wherein said pressure regulator couples to said chamber via a port which passes through said first wall.

74. The method of claim 73, further comprising disposing said port proximate a first wall top end.

75. The method of claim 70, further comprising configuring said pressure regulator as a syringe.

76. The method of claim 52, further comprising extending said needle guide channel through said second wall.

77. The method of claim 48, further comprising configuring said needle guide channel to receive a needle of an injector.

78. The method of claim 77, further comprising configuring said needle guide channel to guide a needle tip of said needle to a predetermined location within an annular member interior space.

79. The method of claim 77, further comprising configuring said needle guide channel to guide a needle tip of said needle to a predetermined target injection location within a cornea when said intraocular injection device is in use.

80. The method of claim 77, further comprising configuring said needle guide channel to guide a needle tip of said needle to a predetermined target injection location between layers of a cornea when said intraocular injection device is in use.

81. The method of claim 77, further comprising configuring said needle guide channel to have a needle guide channel length configured to accommodate a particular said needle having a specific needle length.1148P01T82. The method of claim 77, further comprising configuring said needle guide channel to have a needle guide channel diameter configured to accommodate a particular said needle having a specific needle diameter.

83. The method of claim 77, further comprising providing a stop element configured to stop lengthwise travel of said needle through said needle guide channel.

84. The method of claim 83, further comprising configuring said stop element to contact a hub of said needle to stop said lengthwise travel of said needle through said needle guide channel.

85. The method of claim 48, further comprising non-diametrically disposing said needle guide channel axis within an annular member interior space.

86. The method of claim 48, wherein off-setting said needle guide channel axis from said annular member central longitudinal axis positions a needle tip of a needle received within said needle guide channel proximate a peripheral portion of a cornea when said intraocular injection device is in use.

87. The method of claim 48, further comprising downwardly extending said needle guide channel axis from said needle guide channel entry to said needle guide channel exit.

88. The method of claim 48, further comprising providing an injector couplable to said needle guide channel, said injector configured to inject a fluid.

89. The method of claim 88, wherein said injector comprises a needle.

90. The method of claim 89, further comprising providing a syringe couplable to said needle.

91. The method of claim 48, further comprising outwardly extending a handle from said annular member.

92. A method for separating layers of ocular tissue, comprising:1148P01Tpositioning an intraocular injection device comprising an annular member on an ocular surface to dispose a cornea within an annular member interior space;engaging said intraocular injection device with said ocular surface by applying suction to a chamber disposed within said annular member via a pressure regulator;guiding a needle tip of an injector through an off-set needle guide channel to a predetermined target injection location within a peripheral portion of said cornea; and injecting fluid at said predetermined target injection location via said injector to generate a bubble.

93. The method of claim 92, wherein said cornea is in a live patient, whether human or animal, or in a donor eye.

94. The method of claim 92, wherein said annular member comprises an annular first wall.

95. The method of claim 94, wherein said needle guide channel extends through said first wall, said needle guide channel comprising a central needle guide channel axis which passes through a needle guide channel entry and a needle guide channel exit.

96. The method of claim 95, wherein said needle guide channel axis is off-set from an annular member central longitudinal axis which vertically extends through said annular member such that said needle guide channel axis does not intersect with said annular member central longitudinal axis.

97. The method of claim 92, further comprising separating layers of said cornea.

98. The method of claim 97, further comprising performing Deep Anterior Lamellar Keratoplasty (DALK).

99. The method of claim 97, further comprising performing Descemet’s Membrane Endothelial Keratoplasty (DMEK).

100. The method of claim 97, further comprising performing Descemef s Membrane Anterior Keratoplasty (DMAK).1148P01T101. The method of claim 97, further comprising performing BrightMEM Anterior Keratoplasty (BMAK).

102. The method of claim 97, further comprising performing Pre-Descemet’s Endothelial Keratoplasty (PDEK).

103. The method of claim 97, further comprising performing Bowman’s layer transplantation.

104. The method of claim 97, further comprising separating the Descemet’s membrane and the stroma.

105. The method of claim 104, further comprising removing the epithelium, the Bowman’s layer, and said stroma.

106. The method of claim 104, further comprising preserving said Descemet’s membrane and the endothelium.

107. The method of claim 97, further comprising separating the pre-Descemet’s membrane and the stroma.

108. The method of claim 97, further comprising separating the stroma and the Bowman’s layer.

109. The method of claim 97, further comprising separating said layers of said cornea using hydrodelineation.

110. The method of claim 97, wherein said bubble creates a space between said layers of said cornea.

111. The method of claim 97, further comprising visualizing said cornea via said annular member interior space.

112. The method of claim 92, further comprising coupling said intraocular injection device and said pressure regulator.1148P01T113. The method of claim 92, further comprising generating sub-atmospheric pressure within said chamber via said pressure regulator.

114. The method of claim 92, further comprising guiding said needle tip to a predetermined location within said annular member interior space.

115. The method of claim 92, further comprising coupling said intraocular injection device and said injector.

116. The method of claim 92, further comprising generating said bubble between the Descemet’s membrane and the stroma.

117. The method of claim 92, further comprising generating said bubble between the pre-Descemet’ s membrane and the stroma.

118. The method of claim 92, further comprising generating said bubble between the pre-Descemet’s membrane and the Descemet’s membrane.

119. The method of claim 92, wherein said fluid comprises gas.

120. The method of claim 92, wherein said fluid consists essentially of gas.

121. The method of claim 92, wherein said fluid consists of gas.

122. The method of claim 119, wherein said gas comprises air.

123. The method of claim 119, wherein said gas comprises sulfur hexafluoride (SFe).

124. The method of claim 119, wherein said gas comprises perfluoroethane (C2F6).

125. The method of claim 119, wherein said gas comprises perfluoropropane (CsFs).

126. The method of claim 92, wherein said fluid comprises liquid.1148P01T127. The method of claim 92, wherein said fluid consists essentially of liquid.

128. The method of claim 92, wherein said fluid consists of liquid.

129. The method of claim 126, further comprising performing hydrodissection.

130. The method of claim 126, wherein the viscosity of said liquid is about 0.7 centipoise to about 4,000,000 centipoise at about 37° Celsius.

131. The method of claim 126, wherein the osmolarity of said liquid is about 200 milliosmoles per kilogram to about 400 milliosmoles per kilogram.

132. The method of claim 126, wherein the pH of said liquid is about 6.5 to about 8.5.

133. The method of claim 126, wherein the surface tension of said liquid is about 20 milliNewtons per meter to about 80 milliNewtons per meter.

134. The method of claim 126, wherein the working temperature of said liquid is about 20° Celsius to about 40° Celsius.

135. The method of claim 126, wherein said liquid is optically clear.

136. The method of claim 126, wherein said liquid has a refractive index that is similar to said cornea.

137. The method of claim 126, wherein said liquid has a refractive index that is the same as said cornea.

138. The method of claim 135, wherein said liquid is colored.

139. The method of claim 126, wherein said liquid comprises a balanced salt solution.

140. The method of claim 126, wherein said liquid comprises a viscoelastic fluid.1148P01T141. The method of claim 126, wherein said liquid comprises saline.

142. The method of claim 126, wherein said liquid comprises Ringer’s lactate solution.

143. The method of claim 126, wherein said liquid comprises a perfluorocarbon liquid.

144. The method of claim 126, wherein said liquid comprises a corneal storage medium.

145. The method of claim 92, further comprising generating a type 1 bubble.

146. The method of claim 92, further comprising generating a type 2 bubble.

147. The method of claim 92, further comprising generating a type 3 bubble.

148. The method of claim 92, further comprising disposing a bevel of said needle tip downwardly for injection.

149. The method of claim 92, further comprising monitoring generation of said bubble.

150. The method of claim 92, further comprising trephination of said cornea.

151. The method of claim 92, further comprising dissection and removal of the anterior stroma.

152. The method of claim 92, further comprising paracentesis into said bubble.

153. The method of claim 92, further comprising removal of the remaining stroma.

154. The method of claim 92, further comprising assessing the thickness and / or curvature of said cornea prior to use of said intraocular injection device to facilitate optimal placement of said annular member.1148P01T155. The method of claim 92, further comprising increasing the pressure within said chamber to atmospheric pressure or greater to facilitate disengagement of said intraocular injection device from an eye.

156. The method of claim 155, further comprisinguncoupling saidintraocularinjection device and said eye.

Images