Means and method for suprachoroidal drug delivery to a back of an eye

Abstract

The present invention relates to means and methods for delivering treatment to the back of the eye and, more particularly, but not exclusively, to means and methods for suprachoroidal delivery of treatment to the back of the eye.

Description

[0001] MEANS AND METHOD FOR SUPRACHOROID AL DRUG DELIVERY

[0002] TO A BACK OF AN EYE

[0003] RELATED APPLICATIONS

[0004] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 690,815 filed on 5 September 2024, the contents of which are incorporated herein by reference in their entirety.

[0005] FIELD AND BACKGROUND OF THE INVENTION

[0006] The present invention, in some embodiments thereof, relates to means and methods for delivering treatment to the back of the eye and, more particularly, but not exclusively, to means and methods for suprachoroidal delivery of treatment to the back of the eye.

[0007] It has been a challenge and a need to deliver treatment to the back of the eye in a successful and comprehensive manner while trying to avoid as much as possible adverse events and discomfort to the patient. Successful treatment of ocular diseases depends not only on the development of new therapeutic agents but also on the method of delivering these drugs. Although over the years, retinal drug delivery methods have undergone significant advancements, traditional drug delivery methods have many limitations and complications. Periocular injections, a traditional approach for delivering corticosteroids, have exhibited variable drug diffusion across the sclera, leading to lower effectiveness. Intravitreal (IVT) injections may result in widespread dispersion of drugs throughout the eye, raising concerns about off-target effects and / or possible side effects due to the drug affecting non-target tissues. Additionally, an intact blood-retinal barrier can hinder the movement of drugs from the vitreous to the choroid and retinal pigment epithelium. Moreover, IVT injections are associated with several severe complications, such as elevated intraocular pressure, subconjunctival or vitreous hemorrhage, vitreous incarceration, endophthalmitis, and retinal detachment. Treatment via IVT injections can be expensive due to often need for monthly or bi-monthly dosing. Subretinal injections, while offering targeted drug delivery compared to periocular and IVT injections, require vitrectomy in an operating room setting, followed by retinotomy, and limited retinal detachment to administer therapeutic agents directly into the subretinal space.

[0008] Delivering therapeutics into the suprachoroidal space (SCS) may address key limitations of periocular, intravitreal, and subretinal injections, providing additional targeting and compartmentalization benefits. This delivery route represents a promising route of drug administration for posterior segment diseases of eye. The suprachoroidal space, located between the sclera and the choroid, is an attractive target for pharmacotherapy due to its proximity to the choroid, retinal pigment epithelium, and retina. This space is often referred to as a “virtual space” as it remains “closed” due to intraocular pressure (IOP) and the presence of attaching fibers. However, the introduction of fluid into the space, and / or mechanical cannulation can atraumatically separate the tissues, creating a true space between them referred to as the suprachoroidal space.

[0009] Additional background art includes an article by Rotenstreich Y. et al, titled “A Novel Device for Suprachoroidal Drug Delivery to Retina: Evaluation in Nonhuman Primates” (Translational Vision Science & Technology June 2023, Vol.12, 3. doi:www(dot): / / doi(dot)org / 10.1167 / tvst.12.6.3), disclosing a study for the evaluation of distribution and tolerance of suprachoroidal injection of indocyanine green (ICG) in nonhuman primates (NHPs) using a novel suprachoroidal (SC) delivery technology.

[0010] International Patent Publication N. W02019202603A1 disclosing a device for injection into an interlayer of an organ of a subject. The device includes a needle having a size transitional portion terminating in a sharp needle distal tip. The device also includes an elongated tissue separator that is shiftable in the needle lumen. An actuator shifts the tissue separator in the needle lumen between a first position, in which the separator distal tip is fixedly positioned proximally to the needle distal tip, and a second position in which the separator distal tip is fixedly positioned a predetermined distance distally from the needle distal tip.

[0011] International Patent Publication No. WO2015015467A1 disclosing a device suitable for delivery of a fluid composition to an eye, especially therapeutic compositions, comprising: a hollow needle with a bore having a proximal end and a distal end, said distal end configured to pass into a passage in a sclera of an eye, said bore configured to function as a conduit for a fluid from said proximal end to said distal end, and a solid separator having a distal tip, configured to move inside said bore of said hollow needle allowing said distal tip of said separator to protrude from said distal end of said needle.

[0012] U.S. Patent No. US10285852B2 disclosing methods of subretinal delivery of therapeutic compositions to the eye of a mammal. Also disclosed are devices useful for the subretinal delivery of therapeutic compositions to the eye of a mammal.

[0013] U.S. Patent No. US11752101B2 disclosing an ocular medical injector for drug delivery. A method includes inserting a puncture member of the medical injector into the eye until the puncture member reaches the SCS. The puncture member defines a lumen therethrough. With the puncture member disposed within the SCS, a flexible cannula is advanced distally through the lumen of the puncture member, beyond the distal end portion of the puncture member and along the SCS towards a posterior region of the eye. The flexible cannula has an atraumatic distal tip and defines a lumen therethrough. With the distal tip of the flexible cannula disposed within the SCS beyond a distal end portion of the puncture member, a therapeutic substance is administered to the SCS.

[0014] U.S. Patent Publication No. US20170273827A1 disclosing a microneedle having a proximal end portion and a distal end portion and defines a lumen. The proximal end portion is configured to be coupled to a cartridge to place the lumen in fluid communication with the cartridge. The proximal end portion includes a base surface that is configured to be placed in contact with a surface of a target tissue. The distal end portion of the microneedle includes a beveled surface. The beveled surface defines a tip angle of less than about 20 degrees and a ratio of a bevel height to a bevel width of less than about 2.5.

[0015] SUMMARY OF THE INVENTION

[0016] Following is a non-exclusive list including some examples of embodiments of the invention. The invention also includes embodiments which include fewer than all the features in an example and embodiments using features from multiple examples, also if not expressly listed below.

[0017] Example 1. A method of delivering at least one material to a back of an eye, comprising: a. injecting tangentially said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec; b. maintaining a level of intra-ocular pressure (IOP) of said eye within a normal range during and / or after said injecting.

[0018] Example 2. The method according to example 1, further comprising inserting tangentially a needle cannula of no more than 2mm into an ocular layer in said eye before said injecting.

[0019] Example 3. The method according to example 1 or example 2, further comprising inserting tangentially a needle cannula a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

[0020] Example 4. The method according to any one of examples 1-3, further comprising extending a tissue separator from within said needle cannula into said ocular layer a distance of from 0.3mm to 10mm before said injecting.

[0021] Example 5. The method according to any one of examples 1-4, further comprising requesting from said patient to look in a certain direction before said inserting.

[0022] Example 6. The method according to any one of examples 1-5, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction. Example 7. The method according to any one of examples 1-6, wherein said certain direction is up in relation to said patient.

[0023] Example 8. The method according to any one of examples 1-7, wherein said normal range of IOP is from 1 ImmHg to 21 mmHg.

[0024] Example 9. The method according to any one of examples 1-8, wherein said injecting is painless or almost painless.

[0025] Example 10. The method according to any one of examples 1-9, further comprising assessing a correct position of said needle cannula after said inserting.

[0026] Example 11. The method according to any one of examples 1-10, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

[0027] Example 12. The method according to any one of examples 1-11, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

[0028] Example 13. The method according to any one of examples 1-12, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

[0029] Example 14. A method of painlessly or almost painlessly delivering at least one material to a back of an eye, comprising: a. inserting tangentially a needle cannula of no more than 2mm into an ocular layer in said eye; b. extending a tissue separator from within said sharp tip into said ocular layer a distance of from 0.3mm to 10mm ; c. injecting said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec.

[0030] Example 15. The method according to example 14, wherein said inserting tangentially a needle cannula is to a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

[0031] Example 16. The method according to example 14 or example 15, further comprising maintaining a level of intra-ocular pressure (IOP) of said eye within a normal range during and / or after said injecting.

[0032] Example 17. The method according to any one of examples 14-16, wherein said normal range of IOP is from 1 ImmHg to 2 ImmHg.

[0033] Example 18. The method according to any one of examples 14-17, further comprising requesting from said patient to look to a certain direction before said inserting. Example 19. The method according to any one of examples 14-18, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction.

[0034] Example 20. The method according to any one of examples 14-19, wherein said certain direction is up in relation to said patient.

[0035] Example 21. The method according to any one of examples 14-20, further comprising assessing a correct position of said needle cannula after said inserting.

[0036] Example 22. The method according to any one of examples 14-21, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

[0037] Example 23. The method according to any one of examples 14-22, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

[0038] Example 24. The method according to any one of examples 14-23, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

[0039] Example 25. A method of delivering at least one material to a back of an eye of a patient, comprising: a. requesting from said patient to look to a certain direction; b. inserting tangentially a needle cannula to the sclera of the patient; c. injecting tangentially said at least one material into an ocular layer in said eye.

[0040] Example 26. The method according to example 25, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction.

[0041] Example 27. The method according to example 25 or example 26, wherein said certain direction is up in relation to said patient.

[0042] Example 28. The method according to any one of examples 25-27, wherein said injecting tangentially said at least one material into said ocular layer is characterized by injecting at a flow of from lOpl / sec to lOOpl / sec.

[0043] Example 29. The method according to any one of examples 25-28, further comprising maintaining a level of intra-ocular pressure (IOP) of said eye within a normal range during and / or after said injecting.

[0044] Example 30. The method according to any one of examples 25-29, wherein said normal range of IOP is from 1 ImmHg to 21 mmHg.

[0045] Example 31. The method according to any one of examples 25-30, wherein said inserting tangentially comprises inserting said needle cannula no more than 2mm into said sclera. Example 32. The method according to any one of examples 25-31, wherein said inserting tangentially comprises inserting tangentially said needle cannula a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

[0046] Example 33. The method according to any one of examples 25-32, further comprising extending a tissue separator from within said needle cannula into said sclera a distance of from 0.3mm to 10mm before said injecting.

[0047] Example 34. The method according to any one of examples 25-33, wherein said injecting is painless or almost painless.

[0048] Example 35. The method according to any one of examples 25-34, further comprising assessing a correct position of said needle cannula after said inserting.

[0049] Example 36. The method according to any one of examples 25-35, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

[0050] Example 37. The method according to any one of examples 25-36, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

[0051] Example 38. The method according to any one of examples 25-37, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

[0052] Example 39. A method for ensuring correct positioning of an injector for suprachoroidal delivery of materials, comprising: a. tangentially inserting into an eye a needle cannula having a length of no more than 2mm; b. extending a tissue separator a distance of from 1mm to 5mm from a distal end of said needle canula.

[0053] Example 40. The method according to example 39, further comprising providing a suprachoroidal delivery system comprising said needle cannula having a length of no more than 2mm.

[0054] Example 41. The method according to example 39 or example 40, wherein said needle cannula comprises a length of from 1.5mm to 2mm.

[0055] Example 42. The method according to any one of examples 39-41, wherein said tangentially inserting comprises tangentially inserting until reaching a sleeve stopper.

[0056] Example 43. The method according to any one of examples 39-42, wherein said suprachoroidal delivery system comprises a sleeve stopper.

[0057] Example 44. The method according to any one of examples 39-43, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye. Example 45. The method according to any one of examples 39-44, wherein said tissue separator is flexible.

[0058] Example 46. The method according to any one of examples 39-45, wherein said inserting comprises reaching a sclera layer.

[0059] Example 47. The method according to any one of examples 39-46, wherein said inserting comprises not reaching a choroid layer.

[0060] Example 48. The method according to any one of examples 39-47, wherein said extending comprises reaching a choroid layer.

[0061] Example 49. The method according to any one of examples 39-48, wherein said extending comprises not reaching a retina layer.

[0062] Example 50. The method according to any one of examples 39-49, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye. Example 51. A method of providing a rapid posterior flow suprachoroidal delivery of at least one material, comprising: a. tangentially inserting into an eye a needle cannula having a length of no more than 2mm; b. extending a tissue separator a distance of from 1mm to 5mm from a distal end of said needle canula; c. injecting said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec.

[0063] Example 52. The method according to example 51, further comprising providing a suprachoroidal delivery system comprising said needle cannula having a length of no more than 2mm.

[0064] Example 53. The method according to example 51 or example 52, wherein said needle cannula comprises a length of from 1.5mm to 2mm.

[0065] Example 54. The method according to any one of examples 51-53, wherein said tangentially inserting comprises tangentially inserting until reaching a sleeve stopper.

[0066] Example 55. The method according to any one of examples 51-54, wherein said suprachoroidal delivery system comprises a sleeve stopper.

[0067] Example 56. The method according to any one of examples 51-55, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

[0068] Example 57. The method according to any one of examples 51-56, wherein said tissue separator is flexible. Example 58. The method according to any one of examples 51-57, wherein said inserting comprises reaching a sclera layer.

[0069] Example 59. The method according to any one of examples 51-58, wherein said inserting comprises not reaching a choroid layer.

[0070] Example 60. The method according to any one of examples 51-59, wherein said extending comprises reaching a choroid layer.

[0071] Example 61. The method according to any one of examples 51-60, wherein said extending comprises not reaching a retina layer.

[0072] Example 62. The method according to any one of examples 51-61, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

[0073] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0074] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0075] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings and images. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0076] In the drawings:

[0077] Figures la-c are schematic representations of an exemplary suprachoroidal delivery system, according to some embodiments of the invention;

[0078] Figures 2a-j are schematic illustrations of an exemplary method of delivery using the exemplary suprachoroidal delivery system, according to some embodiments of the invention;

[0079] Figure 3 is a flowchart of an exemplary method of delivery using the exemplary suprachoroidal delivery system, according to some embodiments of the invention; Figure 4 is a flowchart of an exemplary method of ensuring correct suprachoroidal delivery of materials, according to some embodiments of the invention;

[0080] Figure 5 is a flowchart of an exemplary method of providing a rapid posterior flow suprachoroidal delivery of materials, according to some embodiments of the invention; and

[0081] Figures 6a-b are thermal photographs taken during the delivery of materials using the exemplary suprachoroidal delivery system.

[0082] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0083] The present invention, in some embodiments thereof, relates to means and methods for delivering treatment to the back of the eye and, more particularly, but not exclusively, to means and methods for suprachoroidal delivery of treatment to the back of the eye.

[0084] Overview

[0085] An aspect of some embodiments of the invention relates to delivering therapeutic agents (referred just as “materials”) to the back of the eye by tangentially injecting therapeutic agents into the suprachoroidal space. In some embodiments, tangentially injecting therapeutic agents into the suprachoroidal space allows the successful delivery of therapeutic agents to the back of eye. In some embodiments, delivery of materials is done at a first attempt without the need of replacing needle sizes across variation in scleral thickness. In some embodiments, tangentially injecting therapeutic agents into the suprachoroidal space allows for a rapid flow of materials towards the back of the eye, allowing a broad distribution of the materials to the back of the eye, including for example the macula. In some embodiments, delivering therapeutic agents to the back of the eye by tangentially injecting (or substantially tangential) therapeutic agents into the suprachoroidal space does not cause adverse effects, like discomfort to the patient. In some embodiments, tangentially injecting therapeutic agents into the suprachoroidal space does not increase the intraocular pressure (IOP) in the patients and / or maintains a normal level of IOP during and / or after the injection. In some embodiments, maintaining the IOP comprises either keeping the level of IOP that was found in the eye before the injection, or keeping a normal level of IOP during and / or after the injection. In some embodiments, insertion of foreign objects, for example the tissue separator, into the interlayers of the eye contributes to the maintenance of the IOP due to constriction of the blood vessels in the zone of entry.

[0086] An aspect of some embodiments of the invention relates to suprachoroidal delivery for treating posterior segment ocular pathologies. In some embodiments, the delivery is performed in a safe, efficient and consistent access to the suprachoroidal space (SCS). In some embodiments, the suprachoroidal delivery system provides a non-surgical device utilizing a non-sharp tissue separator which, via tangential blunt dissection, opens a channel from the sclera to the choroid to access the SCS. In some embodiments, the delivery is characterized by being rapid delivery to the posterior segment and macula. In some embodiments, the delivery, using the suprachoroidal delivery, is characterized by being safe and having an efficient performance when delivering therapeutic materials, for example, triamcinolone acetonide (TA) in, for example, diabetic patients with macular edema (DME).

[0087] An aspect of some embodiments of the invention relates to the results of a clinical trial in human where patients with DME who did not respond to standard intravitreal (IVT) treatments and met the inclusion and exclusion criteria, were screened and enrolled after providing signed informed consent. In some embodiments, the study eyes were determined according to predefined eligibility criteria, including ETDRS BCVA letter score worse than 35 (Snellen equivalent of 20 / 200 imperial or 6 / 60 metric). Each patient received a single injection into the SCS of 4 mg of TA (Intracinol, Farmigea Ophthalmics Ltd.) in a volume of 100 pl, using the exemplary delivery system. All injections were performed under topical anesthesia without the need for an assistant to perform the injection. Thermal imaging was used to confirm injection into the SCS during the procedure. Following the injection, study eyes were assessed by indirect ophthalmoscopy and imaged with EDLOCT. Intraocular pressure (IOP) was evaluated 30+10 minutes post-injection. Post-injection adverse events (AEs) were assessed. Within 1-hour post-injection, ophthalmic examinations were performed including: ETDRS BCVA, SD-OCT, fundus photography and slitlamp biomicroscopy. Following the injection visit, subjects underwent four follow-up visits on Days 3, 14, 28, and 42.

[0088] Successful suprachoroidal delivery of TA was achieved in all patients, confirmed by realtime thermal imaging which showed a rapid posterior flow of the drug. The injection was well tolerated in all patients; none of the patients reported experiencing pain. No serious adverse events (SAEs) were observed. IOP was assessed at screening, baseline (pre-injection), post-injection and at all on-site follow up visits. In all patients IOP was stable and remained within normal range throughout the study. Central macular thickness (CMT) and BCVA remained stable for all patients over the course of the study.

[0089] This first-in-human study demonstrated the safety, feasibility and tolerability of the suprachoroidal delivery system for the delivery of TA into the SCS in patients with DME in an office setting and with topical anesthesia alone. Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0090] Exemplary suprachoroidal delivery system

[0091] Referring now to Figures la-c, showing schematic representations of an exemplary suprachoroidal delivery system, according to some embodiments of the invention.

[0092] Referring now to Figure la, showing a schematic representation of a general view of an exemplary suprachoroidal delivery system, according to some embodiments of the invention. In some embodiments, an exemplary suprachoroidal delivery system 100 comprises a body 102 comprising a sharp needle 104 at a distal end 106 of the body 102. In some embodiments, the body 102 is sized and shaped to receive a syringe 108 to be inserted at a proximal end 110 of the body 102. In some embodiments, the body 102 optionally comprises a window 112 configured to allow a user to assess the velocity of injection and / or the quantity of materials that have been injected. In some embodiments, the system 100 comprises an actuator 114 located on a top surface of the body 102 in close proximity of the distal end 106 of the body 102. In some embodiments, the actuator 114 is configured to allow extension or retraction of a tissue separator 116 (shown for example in Figure 1c). In some embodiments, the sharp needle 104 comprises three main elements: a sleeve stopper 118, a needle cannula 120 and the tissue separator 116.

[0093] Referring now to Figures lb and 1c, showing a schematic representation of a zoom-in view of a sharp needle of an exemplary suprachoroidal delivery system, according to some embodiments of the invention.

[0094] Figure lb shows the sleeve stopper 118, the needle cannula 120 and the sharp tip 122. In some embodiments, the sleeve stopper 118 is configured to stop the further insertion of the needle cannula 120 beyond the length of the needle cannula 120. In some embodiments, the needle cannula 120 comprises a length calculated to reach a specific interlayer region within the eye, for example to reach the sclera or the area between the sclera and the choroid. In some embodiments, the needle cannula 120 comprises a length of no more than 2mm, for example a length of from about 1.5mm to about 2mm.

[0095] Figure 1c shows the sleeve stopper 118, the needle cannula 120 and the tissue separator 116 in an extended position. In some embodiments, the tissue separator 116 is configured to be extended or retracted from within the needle cannula 120 of the sharp needle 104. Figure lb actually shows the retracted configuration of the tissue separator 116, which is not seen since it is completely inserted (and therefore hid) within the needle cannula 120 of the sharp needle 104. In some embodiments, the most distal end (the tip) of the tissue separator is blunt and / or comprises a blunt geometry, for example comprises non-sharp angles. In some embodiments, the tissue separator is made of a single wire having a diameter of about 0.2mm. The device is configured to allow the separator to protrude from the distal end of the needle to an extent suitable for implementing an embodiment of the teachings herein. In some embodiments, the separator extends from the distal end of the needle from about 0.3 mm to about 10mm, optionally not less than 0.3mm, optionally no more than 10mm. In some embodiments, the separator extends from the sleeve stopper from about 4mm to no more than 5mm. In some embodiments, the artificial passage generated by the extension of the tissue separator is configured for effectively containing, channeling and dispersing fluids therefrom to distant and / or large areas throughout the interlayer region of the eye.

[0096] Further explanations regarding the exemplary suprachoroidal delivery system 100, can be found in International Patent Publication N. W02019202603A1, which are incorporated herein by reference.

[0097] In some embodiments, the system 100 is configured for facilitating low to high- volume fluid dispersions in an interlayer region of the eye, by creating, prior to injection, a directional spaced passage (see Figures 2e-2h) into and through the outer most or anterior organ layer, for example, the sclera optionally with the conjunctiva, and an interlayer region, for example, within choroid layer or / and between choroid and retina of the eye, in an accurate anatomical location, chosen alignment, and predefined dimensions.

[0098] In some embodiments, this artificial passage is configured for effectively containing, channeling and dispersing fluids therefrom to distant and / or large areas throughout the interlayer region of the eye.

[0099] In some embodiments, the passage is oriented at a shallow angle (for example from about 0° to about 30°, or substantially tangential, to the target tissue portion and / or to the interlayer region adjacent to point of entry of the needle into the target tissue portion.

[0100] Exemplary method of delivery of materials using the exemplary suprachoroidal delivery system

[0101] Referring now to Figures 2a-2j and Figure 3, showing schematic illustrations of an exemplary method of delivery using the exemplary suprachoroidal delivery system and a flowchart of exemplary actions done during the method, respectively, according to some embodiments of the invention. Without being bound to theory, performing a tangential injection to eye applies forces to the eye that causes the eye to move inwards (in the direction the user is inserting the needle). On one side, the exemplary suprachoroidal delivery system comprises a sleeve stopper 118 that is compressed against the eye during the delivery procedure, which pushes the eye inwards; on the other side, the flow of materials injected within the layers of the eye might also cause movement of the eye inwards. In some embodiments, a potential advantage of requesting the patient to look towards a certain direction is that the patient actively uses the muscles of the eye during the injection procedure, which provides a counter force to the inwards force applied by the operator. Therefore, requesting from the patient to look at a certain direction will help counteracting the forces applied by the operator of the delivery system. In some embodiments, a potential advantage of requesting the patient to look towards a certain direction is that the counterforces reduce the risk of inadvertent withdrawal of the needle cannula from the insertion point prior to injection. In some embodiments, a potential advantage of requesting the patient to look towards a certain direction is that the counterforces reduce the risk of a backflow (reflux) of material out of the needle insertion point by improving the sealing around the needle cannula.

[0102] In some embodiments, optionally, the direction requested to the patient is upwards, thereby injecting in the exposed quadrant, for example, the inferior quadrant. Without being bound to theory, it has been demonstrated that, due to the palpebral oculogyric reflex, or Bell's reflex, patients tend to deviate the eyes upwards and laterally, while pressure is being applied to the eye. It has been proved that the role of this phenomenon is to protect the cornea. In some embodiments, the direction requested to the patient is upwards, thereby injecting in the inferior quadrant in order to take advantage of the palpebral oculogyric reflex during the procedure and reduce the chances of unwanted eye movements during the delivery procedure.

[0103] In some embodiments, the procedure optionally begins by requesting the patient to look at a certain direction, for example to a direction opposite to the desired injection site (in some embodiments, inferior or superior quadrants) thereby facilitating the access to the injection site (302). In some embodiments, optionally, the direction is upwards, thereby allowing for an injection in the inferior quadrant. Contrary to known prior art techniques that are complex and painful, the process performed with the exemplary suprachoroidal delivery system is easy and without experiencing pain. The operator can ask the patient to look at a certain direction, for example to an opposite direction to the desired quadrant of injection, and continue to perform the injection with less concern that the user will perform sudden moves due to the injection itself, since the procedure is painless or at least without causing any adverse effects. In some embodiments, one or more of the following reasons allow for a painless delivery of materials into the interlayers of the eye:

[0104] The exemplary suprachoroidal delivery system 100 comprises a needle cannula 120 having a length of from about 1.5mm to about 2mm, optionally of no more than 2mm, which allows the delivery system to enter just the right distance into the eye to allow for a successful delivery of materials.

[0105] The exemplary suprachoroidal delivery system 100 comprises a sleeve stopper 118 that stops the insertion of the needle cannula 120, which allows the delivery system to prevent over insertion of the needle cannula 120.

[0106] The exemplary suprachoroidal delivery system 100 comprises a tissue separator that generates a directional passage (see below and Figure 2e), which provides for an initial space for the material to enter and disperse as a thin layer throughout the SCS without generating a significant increase of pressure or a bleb (spatial concentrated area of injected material) and without significantly distancing the adjacent tissue layers from each other (which occurs in perpendicular injections).

[0107] In some embodiments, another potential advantage of the overall delivery system and methods thereof, is that it allows to deliver materials while maintaining the intra-ocular pressure (or while not increasing the intra-ocular pressure). In some embodiments, as explained above, the tissue separator generates a directional passage, which provides for an initial space for the material to enter and disperse as a thin layer throughout the SCS without generating a significant increase of pressure or a spatial concentrated area of injected material (which occurs in perpendicular injections), which then allows to maintain the intra-ocular pressure and / or not increase the intraocular pressure.

[0108] In some embodiments, as mentioned above, the user inserts (304) the exemplary suprachoroidal delivery system 100 into the sclera 206 at a shallow angle (from example from about 0° to about 30°, or substantially tangential), to the target tissue portion and / or to the interlayer region adjacent to point of entry of the needle into the target tissue portion, as shown for example in Figure 2a.

[0109] In some embodiments, optionally, after the needle has been inserted up to the stopper, the user gently lifts the injector parallel to its longitudinal axis and away from the eye globe (as if the eye is hanging from the needle), in order to assess if the tip of the needle is under the sclera or under the conjunctiva. In some embodiments, a potential advantage of doing this is to potentially avoid sub-conjunctival injection. In some embodiments, the user actuates (306) the actuator 114, as schematically shown in Figure 2b.

[0110] In some embodiments, actuation of the actuator 114 causes the tissue separator 116 to extend from the needle, as schematically shown for example in Figures 2c and 2d, thereby generating a directional spaced passage 204. In some embodiments, retraction (308) of the tissue separator provides access to the recently generated directional space passage 204, as schematically shown for example in Figure 2e.

[0111] In some embodiments, as can be seen in Figures 2c-2e, the directional space passage 204 is generated, for example, between the sclera 206 and the choroid 208.

[0112] In some embodiments, the user injects (310) the material 210 by pressing the plunger of the syringe 108, thereby releasing the material within the generated directional space passage 204, as schematically shown in Figures 2f-2g.

[0113] In some embodiments, the volume of material injected is from about 50pl to about 500pl. In some embodiments, the time of injection is from about Isec to about 5sec. In some embodiments, the volumetric flow rate of injection is of from about lOpl / sec to about lOOpl / sec, preferably the volumetric flow rate of injection is of 20pl / sec.

[0114] In some embodiments, the material is then allowed to be absorbed and flow (312) within the tissue, or within an interlayer of an organ of a subject, or within the extra vascular space of the choroid, as schematically shown in Figures 2g and 2h.

[0115] Figures 2i show the material flowing into the interlayer of an organ of a subject, while Figure 2j schematically shows that the injected materials reach all areas of the sphere of the back of the eye, or at least 90% of the areas of the sphere of the back of the eye, (for example, the peripheral and posterior choroid, the macula, etc.).

[0116] In some embodiments, the whole process is performed in a time frame of from about 5 minutes to about 10 minutes, optionally form about 2 minutes to about 15 minutes, optionally from about 1 minute to about 20 minutes - where the time required for the injecting action is from about 10 seconds to about 30 seconds, optionally from about 5 seconds to about 45 seconds, optionally from about 1 second to about 1 minute - preferably the time required for the injecting action is 5 seconds.

[0117] In some embodiments, the exemplary suprachoroidal delivery system allows for a distribution of materials in the back of the eye of from about 75% to 90%, optionally from about 70% to about 95%, optionally form about 65% to about 100%. In some embodiments, the exemplary suprachoroidal delivery system allows for a distribution of materials that covers the back of the eye, including one or more of the peripheral choroid and the macula. In some embodiments, a potential advantage of the exemplary suprachoroidal delivery system and the method thereof, is that it provided a way to deliver materials into the eye more easily and quickly than known techniques in the art. In some embodiments, this is enabled because of the particular configuration of the system and the particular method of use - the use of a needle with a tissue separator that is injected substantially tangential to the tissue that first generates a directional space that provides an easy delivery of the materials with less resistance from the space between the layers to receive the delivered materials, which allows the material flow to the back of the eye more quickly, and in some embodiments to be injected more quickly. In some embodiments, on top of all this, the abovementioned allows for a better and wider distribution of the injected material.

[0118] In some embodiments, another potential advantage of the exemplary system is that it allows flexibility in the process of injecting the materials. In some embodiments, due to the flexible tissue separator, the user is not required to access the tissue at a specific and perfect angle. In some embodiments, as mentioned above, the injection is performed at a substantial tangential angle, for example between 0 degrees and 30 degrees. In some embodiments, a potential advantage of this, is that it allows for higher percentages of success when compared to known prior art techniques with less susceptibility to variation in scleral thickness.

[0119] In some embodiments, another potential advantage of the exemplary system is that it allows the delivery of materials to eye, and more specifically to the back of the eye, without increasing the intraocular pressure (IOP) in the patients and / or maintains a normal level of IOP during and / or after the injection. In some embodiments, normal levels of IOP are from about l lmmHg to about 21mmHg. This allows to inject more materials (for example higher volumes), and allows to inject at higher injection speeds.

[0120] Exemplary method for ensuring correct positioning of an injector for suprachoroidal delivery of materials

[0121] Referring now to Figure 4, showing a flowchart of an exemplary method of ensuring correct positioning of an injector for suprachoroidal delivery of materials, according to some embodiments of the invention.

[0122] In some embodiments, an exemplary method of ensuring correct positioning of an injector for suprachoroidal delivery of materials comprises one or more of the following actions:

[0123] 1. Providing a suprachoroidal delivery system comprising a needle cannula having a length that, once inserted into an eye tangentially, the distal end of the needle cannula will stay within the sclera layer (402). For example, the needle cannula comprises a length of no more than 2mm, optionally from about 1.5mm to about 2mm. In some embodiments, a needle cannula having a length of no more than 2mm enables the needle cannula to enter the sclera without passing to next layer, the choroid. In some embodiments, optionally, the suprachoroidal delivery system comprises a sleeve stopper at the most proximal end of the needle cannula, configured to stop the insertion of the needle cannula once reached the sleeve stopper - thereby restricting an overinsertion of the needle cannula.

[0124] 2. Inserting the needle cannula tangentially to the eye surface (404). In some embodiments, the insertion of the needle cannula tangentially, or essentially tangentially or at an angle of from about 0° to about 30° in relation to the surface of eye, having a length as mentioned above, ensures that the needle cannula reaches the sclera without reaching the next layer, the choroid.

[0125] 3. Extending a tissue separator from within the needle cannula (406) a certain distance. In some embodiments, the needle separator is flexible. In some embodiments, the extension is from about 1mm to about 5mm. In some embodiments, extending the tissue separator a distance as disclosed above ensures that the tissue separator reaches the choroid without reaching beyond the choroid, meaning without reaching the retina.

[0126] At this point, it is ensured that the injector opens a channel to the right location within the eye in order to achieve suprachoroidal delivery of materials.

[0127] In some embodiments, the method provides low susceptibility to variations in scleral thickness, thus enable successful suprachoroidal delivery with first attempt, without replacing needle sizes across variation in scleral thickness.

[0128] Exemplary method of providing a rapid posterior flow suprachoroidal delivery of materials

[0129] Referring now to Figure 5, showing a flowchart of an exemplary method of providing a rapid posterior flow suprachoroidal delivery of materials, according to some embodiments of the invention.

[0130] In some embodiments, an exemplary method of providing a rapid posterior flow suprachoroidal delivery of materials comprises one or more of the following actions:

[0131] 1. Providing a suprachoroidal delivery system comprising a needle cannula having a length that, once inserted into an eye tangentially, the distal end of the needle cannula will stay within the sclera layer (502). For example, the needle cannula comprises a length of no more than 2mm, optionally from about 1.5mm to about 2mm. In some embodiments, a needle cannula having a length of no more than 2mm enables the needle cannula to enter the sclera without passing to the next layer, the choroid. In some embodiments, optionally, the suprachoroidal delivery system comprises a sleeve stopper at the most proximal end of the needle cannula, configured to stop the insertion of the needle cannula once reached the sleeve stopper - thereby restricting an overinsertion of the needle cannula.

[0132] 2. Inserting the needle cannula tangentially to the eye surface (504). In some embodiments, the insertion of the needle cannula tangentially, or essentially tangentially or at an angle of from about 0° to about 30° in relation to the surface of eye, having a length as mentioned above, ensures that the needle cannula reaches the sclera without reaching the next layer, the choroid.

[0133] 3. Extending a tissue separator from within the needle cannula (506) a certain distance. In some embodiments, the needle separator is flexible. In some embodiments, the extension is from about 1mm to about 5mm. In some embodiments, extending the tissue separator a distance as disclosed above ensures that the tissue separator reaches the choroid without reaching beyond the choroid, meaning without reaching the retina.

[0134] 4. Injecting the materials at a flow of from about lOpl / sec to about lOOpl / sec (508). In some embodiments, at this flow the materials are allowed to enter the suprachoroidal space and get absorbed / distributed. In some embodiments, the method allows for the materials to get absorbed / distributed, and optionally reaching the posterior part of the eye, within a period of time of from about 5 seconds to about 5 minutes. Optionally within a period of time of from about 3 seconds to about 10 minutes. Optionally within a period of time of from about 1 second to about 15 minutes.

[0135] At this point, rapid posterior flow is achieved.

[0136] Exemplary results of suprachoroidal delivery in human using the exemplary suprachoroidal delivery system

[0137] The following are the results of a study in humans to evaluate safety and performance of the exemplary suprachoroidal delivery system when delivering triamcinolone acetonide (TA) in patients with Diabetic Macular Edema (DME).

[0138] Introduction to the human trial (ClinicalTrials.gov ID NCT06314217)

[0139] Brief Summary

[0140] This was an open-label pilot device study. The aim of the study was to evaluate the safety and performance of the exemplary suprachoroidal delivery system following single injection of suspension approved for ocular use into the suprachoroidal space.

[0141] The study population was patients diagnosed with diabetic macular edema (DME) that were previously treated. Adult subjects were expected to be enrolled based on the inclusionexclusion criteria. The study will involve 6 visits during a period of 6 weeks.

[0142] Detailed description of the study

[0143] The study involved 6 visits: Screening Visit: Visit 1 (Day -6 to 0); Baseline and Injection Visit: Visit 2 (Day 1); Follow up visits: Visit 3 (Day 3 + 1 Days), Visit 4 (Day 14 + 3 Days), Visit 5 (Day 28 + 3 Days); End of Trial: Visit 6 (Day 42 + 3 Days).

[0144] Patient eligibility was assessed at screening, and the study eye was determined.

[0145] Baseline / Inj ection Visit included a pre-injection examination, injection of TA and postinjection examination. The study eye received the suprachoroidal injection of TA injectable suspension approved for ocular use. The exemplary suprachoroidal delivery system was used for a single administration of 100 pl (4 mg) of TA into the suprachoroidal space in the treatment eye.

[0146] Injections using the exemplary suprachoroidal delivery system were performed by trained and qualified investigators after training.

[0147] Study assessments included: physical examination, vital signs, medical and ocular history, AE and concomitant medication assessment.

[0148] Ophthalmological examination included: Best-corrected visual acuity (BCVA) using the Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity Chart. Intraocular Pressure. Optical coherence tomography (OCT). Fundus photography. Fluorescein angiography. ICG angiography. Slit-lamp biomicroscopy. Dilated indirect ophthalmoscopy. Subjects were be followed for 42 days following injection

[0149] Key Inclusion Criteria: Males and females > 18 years of age with a diagnosis of type 1 or type 2 diabetes mellitus. Diagnosis of DME with confirmed central involvement of > 320 pm for males and > 305 pm for females on Spectralis (Heidelberg) or > 305 pm for males and > 290 pm for females with Cirrus

[0150] (Zeiss) by spectral domain optical coherence tomography (SD-OCT), verified at the screening visit. First three patients: ETDRS BCVA letter score of worse than 35 (Snellen equivalent of 20 / 200 imperial or 6 / 60 metric) in the study eye, and ETDRS BCVA of 60 (Snellen equivalent of 20 / 63 imperial or 6 / 19 metric) or better in the fellow eye. Remaining patients: ETDRS BCVA letter score of worse than 50 (Snellen equivalent of 20 / 100 imperial or 6 / 30 metric) in the study eye, and ETDRS BCVA of 60 (Snellen equivalent of 20 / 63 imperial or 6 / 19 metric) or better in the fellow eye. Have shown no response to three previous Intravitreal (IVT) treatments with anti-vascular endothelial growth factor (VEGF) agents.

[0151] Key Exclusion Criteria: Evidence of macular edema of any cause other than diabetic retinopathy in the study eye. Prior treatment with pan-retinal photocoagulation or focal laser photocoagulation in the study eye within 90 days of screening visit. Intraocular pressure > 21 mmHg or uncontrolled glaucoma (open-angle or angle-closure) in the study eye. History of any prior ophthalmic surgeries in the study eye within 90 days of the screening visit. Previous treatment for DME in the study eye with any intravitreal injection in the 30 days prior to the screening visit. Any previous treatment with Ozurdex® implant in past 6 months. Any previous treatment with Iluvien® or Retisert.™ Current iris neovascularization, vitreous hemorrhage, tractional retinal detachment or epiretinal membrane that contributes to macular edema in the study eye, per PI discretion. Uncontrolled blood pressure. HbAlc >12%.

[0152] Study plan Arms and Interventions Primary Outcome Measures

[0153] Secondary Outcome Measures

[0154] Methods and Performance

[0155] Patients were screened and enrolled after providing signed informed consent forms. Exemplary patients’ demographic details of 3 patients are presented in Table 1 below, just as a non-limiting example. Study eyes were determined based on eligibility criteria. The patients received a single injection of 4 mg of TA (100 pl) using a suprachoroidal delivery system into the suprachoroidal space (SCS). The study eyes were prepared for injection according to the standard of care for IVT injections at the study site, including topical anesthesia administration. All injections were performed under topical anesthesia. Following the injection, study eyes were assessed by indirect ophthalmoscopy and imaged with EDI-OCT. IOP was evaluated 30+10 minutes post-injection. An assessment of post-injection AEs was made. Up to 1-hour post-injection, an ophthalmological examination was performed, including: ETDRS BCVA, SD-OCT, fundus photography and slitlamp biomicroscopy. Thermal imaging was used to assess injection into the suprachoroidal space during injection of exemplary patients 101002 and 101003, as shown for example in Figures 6a and 6b; thermal imaging could not be captured in the first patient due to technical challenges of the imaging.

[0156] Table 1. Demographic Table

[0157] Data includes data from visits 1 to 6 of all the patients (the “Reporting Period”). The data was monitored by an external CRO. No major and no critical protocol deviations were reported.

[0158] Results

[0159] Safety

[0160] Mild subconjunctival hemorrhage in the study eye following the injection was found. The events were resolved spontaneously without any treatment and did not lead to any complications. There were no serious adverse events (SAEs) throughout the Reporting Period.

[0161] Intraocular Pressure (IOP)

[0162] IOP was measured by Goldmann applanation tonometry. The results were recorded in mmHg. IOP was assessed at screening, baseline (pre-inj ection), post-injection and at all on-site follow up visits. In all patients IOP was stable and remained within the normal range in all measurements as presented in Table 2. Table 2. IOP (mmHg)

[0163] Central Macular Thickness (CMT)

[0164] CMT change from baseline was measured by OCT. In all patients, reduction in CMT was observed on OCT up to 14 days following injection as presented in Table 3.

[0165] Table 3. Central Macular Thickness (CMT) in pm

[0166] Best-Corrected Visual Acuity (BCVA) BCVA was measured using the Early Treatment of Diabetic Retinopathy Study (ETDRS)

[0167] Visual Acuity Chart. ETRDS BCVA was assessed at each on-site study visit, in all patients, improvement trend was noted as presented in Table 4.

[0168] Table 4. ETRDS BCVA Suprachoroidal Delivery

[0169] Delivery into the SCS was assessed by imaging and ocular examination performed following the injection. Table 5. Delivery into the SCS, determined by imaging and ocular examination during and post injection.

[0170] In patients 101001 and 101002 thermal camera was used during injection, see Figures 6a-6b. In both patients the TA distribution as seen on the thermal camera was consistent with the expected SCS injection pattern.

[0171] Conclusion of results of the trial

[0172] According to the results presented herein, following enrollment and treatment of the patients, a single injection of 4 mg of TA in 100 pl using a suprachoroidal delivery system as described herein into suprachoroidal space was well-tolerated by the patients throughout the study period (42 days following the injection). In all patients IOP was stable and remained within the normal range. Some mild subconjunctival hemorrhage in the study eye was seen, which resolved spontaneously without any treatment, did not lead to any complications, and did not affect the successful delivery of the drug through the SCS and / or treatment effectiveness. There were no serious adverse events (SAEs) throughout the study period.

[0173] TA was successfully injected into the SCS. In addition, the injection of TA using the suprachoroidal delivery system provided indication of the effectiveness of the treatment. This was observed in reduction in DME 14 days post injection as measured by CMT on OCT in all patients, and improvement trend in visual acuity as measured by ETRDS BCVA in all patients.

[0174] In summary, the trial showed a successful suprachoroidal delivery which was confirmed with thermal imaging and post-injection examinations.

[0175] As used herein with reference to quantity or value, the term “about” means “within ± 10 % of’.

[0176] The terms “comprises”, “comprising”, “includes”, “including”, “has”, “having” and their conjugates mean “including but not limited to”.

[0177] The term “consisting of’ means “including and limited to”.

[0178] The term “consisting essentially of’ means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0179] As used herein, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.

[0180] Throughout this application, embodiments of this invention may be presented with reference to a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as “from 1 to 6” should be considered to have specifically disclosed subranges such as “from 1 to 3”, “from 1 to 4”, “from 1 to 5”, “from 2 to 4”, “from 2 to 6”, “from 3 to 6”, etc.; as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0181] Whenever a numerical range is indicated herein (for example “10-15”, “10 to 15”, or any pair of numbers linked by these another such range indication), it is meant to include any number (fractional or integral) within the indicated range limits, including the range limits, unless the context clearly dictates otherwise. The phrases “range / ranging / ranges between” a first indicate number and a second indicate number and “range / ranging / ranges from” a first indicate number “to”, “up to”, “until” or “through” (or another such range-indicating term) a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numbers therebetween.

[0182] Unless otherwise indicated, numbers used herein and any number ranges based thereon are approximations within the accuracy of reasonable measurement and rounding errors as understood by persons skilled in the art.

[0183] As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0184] As used herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

[0185] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0186] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0187] It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A method of delivering at least one material to a back of an eye, comprising: a. injecting tangentially said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec; b. maintaining a level of intra-ocular pressure (IOP) of said eye within a normal range during and / or after said injecting.

2. The method according to claim 1, further comprising inserting tangentially a needle cannula of no more than 2mm into an ocular layer in said eye before said injecting.

3. The method according to claim 1, further comprising inserting tangentially a needle cannula a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

4. The method according to claim 1, further comprising extending a tissue separator from within said needle cannula into said ocular layer a distance of from 0.3mm to 10mm before said injecting.

5. The method according to claim 2, further comprising requesting from said patient to look in a certain direction before said inserting.

6. The method according to claim 5, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction.

7. The method according to claim 5, wherein said certain direction is up in relation to said patient.

8. The method according to claim 1, wherein said normal range of IOP is from 1 ImmHg to 21 mmHg.

9. The method according to claim 1, wherein said injecting is painless or almost painless.

10. The method according to claim 2, further comprising assessing a correct position of said needle cannula after said inserting.

11. The method according to claim 10, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

12. The method according to claim 1, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

13. The method according to claim 4, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

14. A method of painlessly or almost painlessly delivering at least one material to a back of an eye, comprising: a. inserting tangentially a needle cannula of no more than 2mm into an ocular layer in said eye; b. extending a tissue separator from within said sharp tip into said ocular layer a distance of from 0.3mm to 10mm; c. injecting said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec.

15. The method according to claim 14, wherein said inserting tangentially a needle cannula is to a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

16. The method according to claim 14, further comprising maintaining a level of intraocular pressure (TOP) of said eye within a normal range during and / or after said injecting.

17. The method according to claim 16, wherein said normal range of IOP is from 1 ImmHg to 21 mmHg.

18. The method according to claim 14, further comprising requesting from said patient to look to a certain direction before said inserting.

19. The method according to claim 18, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction.

20. The method according to claim 18, wherein said certain direction is up in relation to said patient.

21. The method according to claim 14, further comprising assessing a correct position of said needle cannula after said inserting.

22. The method according to claim 21, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

23. The method according to claim 14, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

24. The method according to claim 14, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

25. A method of delivering at least one material to a back of an eye of a patient, comprising: a. requesting from said patient to look to a certain direction; b. inserting tangentially a needle cannula to the sclera of the patient; c. injecting tangentially said at least one material into an ocular layer in said eye.

26. The method according to claim 25, wherein said inserting is performed at a quadrant of the eye exposed by said patient looking at said certain direction.

27. The method according to claim 25, wherein said certain direction is up in relation to said patient.

28. The method according to claim 25, wherein said injecting tangentially said at least one material into said ocular layer is characterized by injecting at a flow of from lOpl / sec to lOOpl / sec.

29. The method according to claim 25, further comprising maintaining a level of intraocular pressure (IOP) of said eye within a normal range during and / or after said injecting.

30. The method according to claim 29, wherein said normal range of IOP is from 1 ImmHg to 21 mmHg.

31. The method according to claim 25, wherein said inserting tangentially comprises inserting said needle cannula no more than 2mm into said sclera.

32. The method according to claim 25, wherein said inserting tangentially comprises inserting tangentially said needle cannula a length of from about 1.5mm to about 2mm into an ocular layer in said eye before said injecting.

33. The method according to claim 25, further comprising extending a tissue separator from within said needle cannula into said sclera a distance of from 0.3mm to 10mm before said injecting.

34. The method according to claim 25, wherein said injecting is painless or almost painless.

35. The method according to claim 25, further comprising assessing a correct position of said needle cannula after said inserting.

36. The method according to claim 35, wherein said assessing comprises lifting said needle cannula parallel to a longitudinal axis of said needle cannula and away from said eye.

37. The method according to claim 25, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

38. The method according to claim 33, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

39. A method for ensuring correct positioning of an injector for suprachoroidal delivery of materials, comprising: a. tangentially inserting into an eye a needle cannula having a length of no more than 2mm; b. extending a tissue separator a distance of from 1mm to 5mm from a distal end of said needle canula.

40. The method according to claim 39, further comprising providing a suprachoroidal delivery system comprising said needle cannula having a length of no more than 2mm.

41. The method according to claim 39, wherein said needle cannula comprises a length of from 1.5mm to 2mm.

42. The method according to claim 39, wherein said tangentially inserting comprises tangentially inserting until reaching a sleeve stopper.

43. The method according to claim 40, wherein said suprachoroidal delivery system comprises a sleeve stopper.

44. The method according to claim 39, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

45. The method according to claim 39, wherein said tissue separator is flexible.

46. The method according to claim 39, wherein said inserting comprises reaching a sclera layer.

47. The method according to claim 39, wherein said inserting comprises not reaching a choroid layer.

48. The method according to claim 39, wherein said extending comprises reaching a choroid layer.

49. The method according to claim 39, wherein said extending comprises not reaching a retina layer.

50. The method according to claim 39, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

51. A method of providing a rapid posterior flow suprachoroidal delivery of at least one material, comprising: a. tangentially inserting into an eye a needle cannula having a length of no more than 2mm; b. extending a tissue separator a distance of from 1mm to 5mm from a distal end of said needle canula; c. injecting said at least one material into an ocular layer in said eye at a flow of from lOpl / sec to lOOpl / sec.

52. The method according to claim 51, further comprising providing a suprachoroidal delivery system comprising said needle cannula having a length of no more than 2mm.

53. The method according to claim 51, wherein said needle cannula comprises a length of from 1.5mm to 2mm.

54. The method according to claim 51, wherein said tangentially inserting comprises tangentially inserting until reaching a sleeve stopper.

55. The method according to claim 52, wherein said suprachoroidal delivery system comprises a sleeve stopper.

56. The method according to claim 51, wherein said inserting is performed at an angle from 0° to 30° in relation to the surface of the eye.

57. The method according to claim 51, wherein said tissue separator is flexible.

58. The method according to claim 51, wherein said inserting comprises reaching a sclera layer.

59. The method according to claim 51, wherein said inserting comprises not reaching a choroid layer.

60. The method according to claim 51, wherein said extending comprises reaching a choroid layer.

61. The method according to claim 51, wherein said extending comprises not reaching a retina layer.

62. The method according to claim 51, wherein said extending generates an artificial passage configured for containing, channeling and dispersing said at least one material therefrom to distant and / or large areas throughout the interlayer region of said eye.

Images