Ophthalmic Devices

Abstract

Disclosed herein is a drug-eluting ophthalmic device comprising a body having a posterior surface and an anterior surface, the size of the body, the shape of the posterior surface, and the shape of the anterior surface configuring the device to reside on the bulbar conjunctiva of the eye.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 012,388, filed April 20, 2020, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] The present invention, in some embodiments thereof, relates to ophthalmic devices, and more particularly, but not exclusively, to drug-eluting ophthalmic devices.

[0003] Lang, JC, "Ocular Drug Delivery: Conventional Ocular Formulations," Adv. Drug Delivery, 1995, 16:39-43, states: "Only about 5% of a drug administered intravenously penetrates the cornea and reaches the ocular tissues, while the remainder is lost through tear drainage. Upon instillation, the drug mixes with the fluid present in the tear film, and its residence time in the film is short, approximately 2 to 5 minutes. Approximately 5% of the drug is absorbed, and the remainder flows through the superior and inferior canaliculi into the lacrimal sac. The drug, along with the tears, is transported from the lacrimal sac to the nasolacrimal duct, where it is absorbed and reaches the bloodstream. This absorption leads to drug wastage, and the presence of certain drugs in the bloodstream can cause undesirable side effects." For example, the prescribing information for TIMPOTIC® from Merck states, "Beta-receptor blockers, such as timolol, used to treat wide-angle glaucoma, can have adverse cardiac effects."

[0004] Furthermore, for example, Segal, M., "Patches, pumps and timed release," FDA Consumers magazine, October 1991, states that "administration of eye medications via intravenous drops causes rapid changes in the rate of drug delivery to the cornea that limit the effectiveness of the therapeutic system."

[0005] Benjamin J Hearne's "Eye care in the intensive care unit," Journal of the Intensive Care Society 2018, states: "Ocular surface disease is common in the intensive care population, with 20-42% of patients suffering from corneal epithelial defects. Despite the scale of the problem, eye care protocols are not commonly implemented, and eye care documentation is often inadequate. The majority of corneal problems encountered in the intensive care unit can be prevented by adhering to precise eye care practices. For example, management of conjunctivitis requires application of chloramphenicol ointment to the eyes four times daily for five to seven days."

[0006] The use of intraocular inserts of various shapes to treat eye disorders is clearly known.

[0007] Katz, US Patent No. 4,343,787, describes "the fabrication of a device for insertion under the lower eyelid to treat dry eye syndrome using a water-soluble polymer."

[0008] Ness, US Patent No. 3,618,604, describes a "small, generally crescent-shaped product that fits under the lower eyelid and is used to distribute medication in the eye."

[0009] Bawa's US Patent No. 5,137,728 specifies "an insert having a base curve that is steeper than the radius of curvature of the eye, more precisely a radius of curvature that is less than 0.8 times the radius of the eye."

[0010] Tapolsky's U.S. Patent No. 7,579,019 states: "An insert having a mucoadhesive layer. The mucoadhesive layer aids in attachment of the device. Apparently, in the described design, the mucoadhesive layer tends to erode quickly, obviously affecting the residence time of the device."

[0011] Further background art includes: U.S. Patent No. 3,995,635, U.S. Patent No. 3,867,519, U.S. Patent No. 3,828,777, U.S. Patent No. 3,854,480, U.S. Patent No. 4,571,039, U.S. Patent No. 4,484,922, U.S. Patent No. 4,592,752, Bourlais, CL, Acar, L., Zia H., Sado, PA, Needham, T., Leverge, R., “Ophthalmic drug delivery systems”, Progress in retinal and eye research, 1998, 17, 1:33-58, Richard T Addo et al. “Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery”, J Pharm Sci.2015 May;104(5):1677-90, “Development of Water-Compatible Molecularly Imprinted Polymers Based on Functionalized β-Cyclodextrin for Controlled Release of Atropine” by Yahui He et al., Polymers 2020, 12(1), 130. Sunil A Agnihotri 1, Tejraj M Aminabhavi, “Chitosan nanoparticles for prolonged delivery of timolol maleate”, Drug Dev Ind Pharm. 2007 Nov;33(11):1254-62, and James P Bertram 1, Sandeep S Saluja, Jodi McKain, Erin B Lavik, “Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid) / poly(lactic acid) microspheres for over 3 months”, J Microencapsul.2009 Feb;26(1):26. Summary of the Invention [Means for solving the problem]

[0012] Below is a non-exhaustive list including some example embodiments of the present invention. The present invention also includes embodiments including fewer than all of the features in the examples and embodiments that use features from more than one example, even if not explicitly listed below.

[0013] Example 1. An ophthalmic device comprising a body having a posterior surface and an anterior surface, wherein the size of the body, the shape of the posterior surface, and the shape of the anterior surface configure the device to remain on the bulbar conjunctiva of the eye.

[0014] Example 2. The device of Example 1, wherein when resting on the bulbar conjunctiva, the posterior surface is adjacent to the bulbar conjunctiva and the anterior surface is at least periodically adjacent to the inner surface of the eyelid.

[0015] Example 3. A device described in any one of Examples 1 to 2, wherein the body has a therapeutic substance and is configured to elute the therapeutic substance into the eye when the body is in contact with the bulbar conjunctiva.

[0016] Example 4. The device of any one of Examples 1 to 3, wherein the body has a size of 2 to 8 mm.

[0017] Example 5. The device of any one of Examples 1-4, wherein the body has a thickness of less than 400 microns.

[0018] Example 6. A device according to any one of Examples 1 to 5, wherein an edge region of the body less than 0.5 mm from the edge of the body has a thickness of less than 50 microns.

[0019] Example 7. The device of any one of Examples 1-6, wherein the posterior surface is concave.

[0020] Example 8. The device of any one of Examples 1-7, wherein the ratio of the radius of curvature of the posterior surface to the radius of curvature of the sclera of the eye is greater than 0.8.

[0021] Example 9. The device of any one of Examples 1 to 8, wherein the radius of curvature of the posterior surface is 9 to 11 mm.

[0022] Example 10. The device of any one of Examples 1 to 9, wherein the flexibility of the device is 0.3 to 1.5 MPa.

[0023] Example 11. The device of any one of Examples 1 to 10, wherein the front surface is convex.

[0024] Example 12. The device of any one of Examples 1 to 11, wherein the radius of curvature of the anterior surface is smaller than the radius of curvature of the posterior surface.

[0025] Example 13. The device of any one of Examples 1 to 12, wherein the device is configured to remain on the ocular surface for at least 15 minutes.

[0026] Example 14. The device of any one of Examples 1 to 13, wherein the bulbar conjunctiva is a portion of the conjunctiva between the cornea and the forniceal conjunctiva.

[0027] Example 15. A device according to any one of Examples 1 to 14, wherein the bulbar conjunctiva is a portion of the conjunctiva coinciding with the tear meniscus.

[0028] Example 16. The device of any one of Examples 1-15, wherein the posterior surface comprises a mucoadhesive material.

[0029] Example 17. The device of any one of Examples 1 to 16, wherein the front surface has a smooth surface and / or comprises a lubricating material.

[0030] Example 18. A device described in any one of Examples 1 to 17, wherein the body comprises a material that disintegrates in the eye.

[0031] Example 19. A device described in any one of Examples 1 to 18, wherein the body comprises one or both of a biodegradable material and a bioerodible material.

[0032] Example 20. The device of any one of Examples 1 to 19, wherein the rear surface has one or more cavities.

[0033] Example 21. The device of any one of Examples 1 to 20, wherein the rear surface has one or more protrusions.

[0034] Example 22. The device of any one of Examples 1 to 21, wherein the device comprises one or more electronic elements.

[0035] Example 23. The device of any one of Examples 1 to 22, wherein the device is provided in a dry or semi-hydrated state.

[0036] Example 24. The device of any one of Examples 1 to 23, wherein the device is hydrated on the ocular surface.

[0037] Example 25. A device described in any one of Examples 1 to 24, wherein the body has two or more layers having different material properties.

[0038] Example 26. The device of any one of Examples 1 to 25, wherein the body comprises one or more of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinyl alcohol (PVOH), polyethylene glycol (PEG), cellulose acetate (CA), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat), polyacrylic acid (e.g., Carbopol or Carbomer), hyaluronic acid, ethyl cellulose, triethyl citrate (TEC), glycerol, dextran, and combinations thereof.

[0039] Example 27. A device described in any one of Examples 1 to 26, wherein the device has one or more anchors configured to hold the device on the bulbar conjunctiva.

[0040] Example 28. The device described in Example 27, wherein the anchor has a sharp edge on the body.

[0041] Example 29. The device of Example 28, wherein the radius of curvature of the edge is less than 100 microns.

[0042] Example 30. The device of any one of Examples 1 to 29, wherein the rear surface is rough.

[0043] Example 31. An ophthalmic device having a body configured to remain on the bulbar conjunctiva, the body having a concave posterior surface, the ratio of the radius of curvature of the posterior surface to the radius of curvature of the sclera of the eye being greater than 0.8.

[0044] Example 32. An ophthalmic device having a body configured to remain on the bulbar conjunctiva, the body having a size of 2 to 8 mm and an edge region less than 0.5 mm from the edge of the body, the edge region having a thickness of less than 50 microns.

[0045] Example 33. A method comprising: attaching an ophthalmic device to the bulbar conjunctiva of an eye; and performing a diurnal activity during a period in which the ophthalmic device remains in place on the bulbar conjunctiva of the eye.

[0046] Example 34 The method of Example 33, wherein the performing does not cause discomfort to the eyes.

[0047] Example 35. The method of any one of Examples 33-34, wherein the device remains in place during blinking and tearing.

[0048] Example 36. The method of any one of Examples 33-35, wherein during blinking, the step between the edge of the device and the bulbar conjunctiva deflects the eyelid outward up to 400 microns from the bulbar conjunctival surface.

[0049] Example 37. The method of any one of Examples 33 to 36, wherein the device moves a maximum of 0.5 mm from its resting position on the bulbar conjunctiva.

[0050] Example 38. The method of any one of Examples 33 to 37, wherein the applying comprises applying pressure to the device when the device is in contact with the bulbar conjunctiva.

[0051] Example 39. The method of any one of Examples 33-38, comprising removing the device from the eye after the dwell period.

[0052] Example 40. The method of any one of Examples 33 to 39, comprising ejecting the device.

[0053] Example 41. The method of any one of Examples 33-40, comprising attaching an additional ophthalmic device.

[0054] Example 42. The method of Example 41, wherein the applying is during or after the residence time.

[0055] Example 43. A method of treatment comprising covering a portion of the bulbar conjunctiva with an ophthalmic device for a dwell period.

[0056] Example 44. The method of Example 43, wherein the residence time is from 1 hour to 1 week.

[0057] Example 45. The method of any one of Examples 43-44, comprising eluting a drug from the body of the ophthalmic device into one or both of the tear fluid and the ocular tissue.

[0058] Example 46. The method of any one of Examples 43-45, comprising adhering the ophthalmic device to the bulbar conjunctiva.

[0059] Example 47 The method of Example 46, wherein the adhering comprises mucoadhesion of the posterior surface of the device to the bulbar conjunctiva.

[0060] Example 48. The method of any one of Examples 46-47, wherein the attaching comprises suction caused by surface tension resulting from the difference in curvature between the posterior surface of the device and the bulbar conjunctiva.

[0061] Example 49. The method of any one of Examples 46 to 48, wherein the attaching step includes securing the device by digging the edge of the device into the bulbar conjunctiva.

[0062] Example 50. The method of any one of Examples 46 to 49, wherein the adhering comprises sucking one or more portions of the bulbar conjunctiva under surface tension toward and / or into one or more cavities on the posterior surface of the device.

[0063] Example 51. A method described in any one of Examples 46 to 50, wherein the attaching includes fixing the device by digging one or more protrusions located on the posterior surface of the device into one or more portions of the bulbar conjunctiva.

[0064] Example 52. The method of any one of Examples 43 to 51, comprising exposing the device to tear fluid and movement of the eyeball and eyelid, thereby causing the device to degrade during the dwell period.

[0065] Example 53 The method of Example 52, wherein the degradation reduces adhesion of the device to the bulbar conjunctiva.

[0066] Example 54. The method of any one of Examples 52-53, wherein the degrading comprises the device breaking down into parts smaller than the initial size of the device.

[0067] Example 55. A method comprising applying a dry or partially hydrated ophthalmic device to the surface of an eye and hydrating the device within the eye.

[0068] Example 56 The method of Example 55, wherein the hydrating is performed by one or more of the following: tears in the eye and applying a hydrating fluid to the eye.

[0069] Example A. An ocular device having a rear surface and a front surface, with one or more cavities opening to the rear surface.

[0070] Example B. An ocular device as described in Example A, for protective or therapeutic purposes.

[0071] Example C. An ocular device of any one of Examples A-B containing a therapeutic agent or other compound.

[0072] Example D. An ocular device according to any one of Examples A-C, having a posterior mucoadhesive surface.

[0073] Example E. An ocular device according to any one of Examples A-D, having a smooth front surface.

[0074] Example F. An ocular device according to any one of Examples A-E, having a comfort or tight edge design.

[0075] Example G. An ocular device according to any one of Examples A-F, having one or more protrusions on the rear surface.

[0076] Example H. An ocular device according to any one of Examples A-G, intended for insertion into the eye.

[0077] Example I. An ocular device according to any one of Examples A-H that is biodegradable or bioerodible.

[0078] Example J. The ocular device of any one of Examples A-I, having a thickness of 200 microns or less.

[0079] Example K. The ocular device of any one of Examples A-J, in a dry state.

[0080] Example L. An ocular device according to any one of Examples A-K configured to release a drug while in the eye / on the cornea without interfering with the patient's vision.

[0081] Example M. An ocular device of any one of Examples A-L designed to adhere to the sclera, cornea, limbus, or conjunctiva.

[0082] 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 this invention belongs. Although in some embodiments, methods and materials similar or equivalent to those described herein are used in the practice or testing of the present invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. Furthermore, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0083] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. Referring now specifically to the drawings, it is emphasized that the details shown are by way of example and for purposes of illustrating embodiments of the invention. In this regard, the description using the drawings will make apparent to those skilled in the art how embodiments of the invention may be practiced. [Brief explanation of the drawings]

[0084] [Figure 1A] 1 is a simplified schematic cross-sectional view of an ophthalmic device in place on an eye according to some embodiments of the present invention. [Figure 1B] 1A-1C are simplified schematic top views of an ophthalmic device in place on an eye according to some embodiments of the present invention. [Figure 1C] 1 is a simplified diagram of an ophthalmic device in place on an eye, according to some embodiments of the present invention. [Figure 1D] 1 is a simplified diagram of an ophthalmic device in place on an eye, according to some embodiments of the present invention. [Figure 2] 1 is a method of using an ophthalmic device according to some embodiments of the present invention. [Figure 3] 1 is a method of using an ophthalmic device according to some embodiments of the present invention. [Figure 4] 1 is a simplified schematic cross-sectional view of an ophthalmic device on the surface of the eye according to some embodiments of the present invention. [Figure 5A] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 5B] 1 is a simplified schematic side view of an ophthalmic device according to some embodiments of the present invention. [Figure 5C] 1 is a simplified schematic cross-sectional view of an ophthalmic device according to some embodiments of the present invention. [Figure 5D] 1 is a simplified schematic diagram of an ophthalmic device according to some embodiments of the present invention. [Figure 6]1A-1C are simplified schematic cross-sectional views of edge portions of ophthalmic devices according to some embodiments of the present invention. [Figure 7] 1A-1C are simplified schematic cross-sectional views of edge portions of ophthalmic devices according to some embodiments of the present invention. [Figure 8] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 9] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 10] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 11] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 12] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 13] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 14] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 15] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 16] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 17] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 18A] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 18B] 1 is a simplified schematic diagram of an ophthalmic device according to some embodiments of the present invention. [Figure 18C] 1 is a simplified schematic cross-sectional view of an ophthalmic device according to some embodiments of the present invention. [Figure 19]1 is a simplified schematic cross-sectional view of an ophthalmic device according to some embodiments of the present invention. [Figure 20] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 21] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 22] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 23] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 24] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 25] 1 is a simplified schematic bottom view of an ophthalmic device according to some embodiments of the present invention. [Figure 26] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 27] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 28] 1A-1C are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention. [Figure 29A] 1 is a simplified schematic cross-sectional view of a portion of the surface of an eye, according to some embodiments of the present invention. [Figure 29B] 1 is a simplified schematic cross-sectional view of an ophthalmic device on the surface of the eye according to some embodiments of the present invention. [Figure 29C] 1 is a simplified schematic cross-sectional view of an ophthalmic device on the surface of the eye according to some embodiments of the present invention. [Figure 30] 1A-C are simplified schematic cross-sectional views of a portion of a device on the surface of the eye, according to some embodiments of the present invention. [Figure 31A] 1 is a simplified schematic cross-sectional view of an ophthalmic device on the surface of the eye according to some embodiments of the present invention. [Figure 31B] 1 is a simplified schematic diagram of an ophthalmic device according to some embodiments of the present invention. [Figure 31C] 1A-1C are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention. [Figure 32] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 33] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 34] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 35] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 36] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 37] 1A-1C are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention. [Figure 38] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 39] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 40] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 41] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 42] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 43] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 44] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 45]1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 46] 1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 47] 1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 48] 1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 49] 1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 50] 1 is a simplified schematic cross-sectional view of a dual layer device according to some embodiments of the present invention. [Figure 51] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 52] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 53] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 54] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 55] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 56] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 57] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 58] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 59] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 60]1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 61] 1 is a simplified schematic cross-sectional view of a multi-layer device according to some embodiments of the present invention. [Figure 62] 1A-F are simplified schematic cross-sectional views of a portion of a device over time as the device dwells, according to some embodiments of the present invention. [Figure 63] 10 is a flowchart of the decay progression of a device, according to some embodiments of the present invention. [Figure 64] 1A-C are simplified schematic cross-sectional views of a device over time according to some embodiments of the present invention. [Figure 65] 5A-D are simplified schematic cross-sectional views of a device according to some embodiments of the present invention over a period of residence time for the device. [Figure 66] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 67] 1 is a simplified schematic cross-sectional view of a device according to some embodiments of the present invention. [Figure 68] 8A-B are simplified schematic cross-sectional views of a device on the surface of the eye according to some embodiments of the present invention. [Figure 69] 1 is a method of manufacturing an ophthalmic device according to some embodiments of the present invention. [Figure 70] 1 is a method of manufacturing a film according to some embodiments of the present invention. [Figure 71] 5A-D are simplified schematic cross-sectional views of portions of devices according to some embodiments of the present invention. [Figure 72] 1 is a method of manufacture according to some embodiments of the present invention. [Figure 73] 1A-1D are simplified schematic cross-sectional views of films according to some embodiments of the present invention, and 1E-1F are simplified schematic cross-sectional views of devices according to some embodiments of the present invention. [Figure 74]1A-C are simplified schematic cross-sectional views of devices according to some embodiments of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0085] The present invention, in some embodiments thereof, relates to ophthalmic devices, and more particularly, but not exclusively, to drug-eluting ophthalmic devices.

[0086] overview A broad aspect of some embodiments relates to an ophthalmic device for treating and / or protecting the eye, where the ophthalmic device remains on the eye when attached to the surface of the eye (e.g., the sclera). For example, the ophthalmic device does not move from the area of ​​attachment on the surface of the eye and / or is not expelled from the eye during the treatment period. At the same time, in some embodiments, the device remains comfortable for the user to wear.

[0087] In some embodiments, the ocular device remains in place after initial implantation, e.g., during a dwell time, moving, e.g., up to 0.5 mm to 5 mm, or 0.5 mm to 1 mm, or a shorter, longer, or intermediate range or distance, on the surface of the eye from the attachment and / or dwell position.

[0088] In some embodiments, the device remains on and / or in place over the eye during normal activities of the subject, such as one or more of blinking, tearing, crying, sweating, washing (e.g., showering), walking, exercising, sleeping, etc. In some embodiments, the device remains on and / or in place over the eye while the eye is primarily closed, e.g., during sleep, and / or when the patient is semi-conscious or unconscious.

[0089] An aspect of some embodiments of the present invention relates to an ophthalmic device provided in a dry state, the device comprising one or more therapeutic agents. In some embodiments, the device is provided in a semi-hydrated state (including, for example, a partially hydrated state and / or a humidified state).

[0090] A potential advantage of an anhydrous and / or hypohydrated device is reduced degradation of the therapeutic agent(s) during storage of the ophthalmic device, e.g., after manufacture and before use, e.g., in some embodiments, extended shelf life. In some embodiments, the device is flexible in its dry state, and in some embodiments, the flexibility allows the device to be placed on the eye without prior hydration and / or softening.

[0091] In some embodiments, when the device is hydrated it increases in size and / or changes shape.

[0092] In some embodiments, the ophthalmic device comprises one or more therapeutic agents and / or other compound(s) that are released during the device's residence on the eye. In some embodiments, the therapeutic agent(s) elute from the device when the device is on the surface of the eye. In some embodiments, upon installation, the device adheres to the upper ocular mucosal surface of the eye, providing protection and / or localized drug delivery to the eye. In some embodiments, the ophthalmic device comprises one or more therapeutic agents in a modified release form.

[0093] In some embodiments, the ophthalmic device is placed on the sclera above or below the cornea. In some embodiments, the ophthalmic device is placed on the bulbar conjunctival portion of the sclera, which is the surface of the eye located between the cornea and the conjunctival fornix. In some embodiments, the device is placed outside the conjunctival sac of the eye, or at most partially within the conjunctival sac of the eye. In some embodiments, the device is placed sufficiently close to the cornea to receive eyelid movement during blinking or eye movement. In some embodiments, the device is visible when the eye is in a relaxed, open position. In some embodiments, the device adheres sufficiently to the surface of the eye to be placed in an area that is not within the conjunctival sac of the eye and / or is not entirely within the conjunctival sac.

[0094] In some embodiments, the device is positioned in the region of the tear meniscus of the eye and / or in the region where the meniscus is present most of the time, e.g., at least 50% of the time, where in some embodiments the position of the meniscus is defined by the position of the lower eyelid, and in some embodiments, such that the eyelid does not cover the device, e.g., not even partially, when the eye is wide open.

[0095] In some embodiments, the device is placed outside of the region(s) described in the above two paragraphs and moves into the region(s), e.g., in less than 1 minute to 1 hour, after which, in some embodiments, the device continues to move in vivo, e.g., up to 0.5-5 mm, or 0.5-1 mm, during the device's dwell time.

[0096] A potential advantage of placement of the device is contact with high fluid volume (e.g., tears) and / or high fluid movement, e.g., shortening the therapeutic substance delivery time and / or optionally the disintegration time and / or optionally the residence time of the device.

[0097] A potential advantage of placing a device on the bulbar conjunctiva is that the bulbar conjunctiva has a firmer surface, compared to, for example, the wrinkled and / or slippery fornix conjunctiva. Potentially, the smooth and / or firm surface of the bulbar conjunctiva requires less force to hold the device firmly in place on the sclera, compared to, for example, the fornix conjunctiva and / or the conjunctiva in the conjunctival sac of the eye. Potentially, this allows for the use of a flatter device (e.g., the ratio of the radius of curvature of the posterior surface of the device to the conjunctiva is less than 0.8 in some embodiments). A potential advantage of placing a device on the bulbar conjunctiva, rather than, for example, the conjunctival sac of the eye, is easier application of the device. For example, the device may be applied without one or more of tilting the eye and / or retracting the eyelid and / or using an applicator.

[0098] In some embodiments, the device (e.g., the curvature of one or more portions of the device that creates sufficient suction to hold the device in place) conforms to a sufficiently firm and / or smooth ocular surface, e.g., the bulbar conjunctiva rather than the forniceal conjunctiva.

[0099] A potential advantage of the described device placement is that the device causes limited or no visual obstruction to the patient.

[0100] Generally, the sclera in the bulbar conjunctival region and the cornea have different radii of curvature, with the curvature change occurring in the limbal region. A device with a thin edge (e.g., including one or more features described herein) can be attached to the sclera, potentially preventing the device from lifting from the sclera and / or limbus onto the cornea, potentially securing the device in place and / or preventing the device from obstructing the patient's vision.

[0101] In some embodiments, thin devices having a size (e.g., diameter) of 2-8 mm, adhere to the sclera (e.g., as described herein), and / or have a low profile around the surface of the eye (e.g., at the device edge) are potentially less likely to be expelled from the eye. In this regard, in some embodiments, the device profile on the surface of the eye (e.g., at the device edge) involves one or both of a thin edge of the device and / or an edge that is embedded into the surface of the eye. In some embodiments, the step formed between the edge of the device and the surface of the eye is 1-100 microns, or 10-50 microns, or smaller, larger, or an intermediate range or step. In some embodiments, this step causes the eyelid (or both eyelids, e.g., in the case of annular and / or partially annular devices that cover the bulbar conjunctiva) to deflect when the patient blinks.

[0102] In some embodiments, the edge characteristics (e.g., shape and / or thickness) described herein cover all or a portion of the edge region of the device. For example, they cover a portion of the peripheral edge of the device. For example, they cover 20-99%, or 80-90%, or a lower, higher, or intermediate range or percentage around the device. In some embodiments, different portions of the peripheral edge of the device have different characteristics, e.g., shape and / or thickness.

[0103] In some embodiments, adhesion to the sclera involves adhesion of the edges of the device to the sclera, and is influenced, for example, by the degree to which the device conforms to the sclera and / or the degree to which the sclera conforms to the device. In some embodiments, the device includes one or more features that enhance adhesion between the device and the sclera, for example, by including, for example, roughness and / or fasteners (e.g., cavities, protrusions, and / or hooks) located on the posterior surface and / or edges of the device.

[0104] For example, the edge of the eyelid may not be able to grasp the ocular device and / or push the ocular device and / or move the ocular device to the edge of the eye (eyelid commissure) and / or manipulate the device to eject it.

[0105] One aspect of some embodiments relates to an ophthalmic device that adheres to the surface of the eye. In some embodiments, the device includes one or more features that enhance adhesion of the device to the surface of the eye. Additionally or alternatively, in some embodiments, the device includes one or more features that reduce removal forces experienced by the device, such as those associated with a subject blinking, tearing, and / or rubbing the eye.

[0106] A potential advantage of ophthalmic device attachment is the reduction and / or elimination of device mobility, for example, allowing the device to select a fixed location to reside and / or allow the device to treat selected portions of the eye.

[0107] A potential benefit of adhesion of an ophthalmic device is that it increases the residence time of the device on the surface of the eye. Without wishing to be bound by theory, it is hypothesized that increased adhesion of the device to the surface of the eye reduces fluid flow between the device and the eye. Potentially, reduced fluid flow increases the residence time of the device.

[0108] In some embodiments, the body of the ophthalmic device has a concave posterior surface. In some embodiments, the body has a convex anterior surface.

[0109] In some embodiments, the concave surface of the posterior surface that contacts the surface of the eye (e.g., the sclera) enhances adhesion of the device to the surface of the eye. The concave surface, for example, creates an attractive force between the device and the surface of the eye, adhering the device to the surface of the eye. Optionally, in some embodiments, the radius of curvature of one or more portions of the posterior surface of the device is smaller than the radius of curvature of the portion of the eye to which the device adheres, for example, smaller than the radius of curvature of the sclera.

[0110] In some embodiments, for example, the posterior surface is smooth, potentially reducing irritation associated with contact of the device with the ocular surface. In some embodiments, the posterior surface includes roughened portion(s) and / or retainer(s), potentially enhancing adhesion due to friction between the posterior surface and the ocular surface. In some embodiments, the edge region of the posterior surface (e.g., optionally, but not in some embodiments, the smooth central region) is roughened and / or includes retainer(s) and / or protrusions and / or cavities.

[0111] In some embodiments, the device remains in place despite having a posterior surface with a small radius of curvature, e.g., the ratio of the radius of curvature of the posterior surface to the radius of curvature of the eye is 0.6 to 0.95, or 0.8 to 0.95, or 0.8 to 1, or greater than about 0.8, or less than, or greater than, or any intermediate range or ratio. For example, the radius of curvature of the posterior surface is the same as or greater than the radius of curvature of the portion of the eye to which the device adheres, e.g., the radius of curvature of the sclera. For example, in some embodiments, the device remains in place despite having a flat or convex posterior surface, e.g., by one or more of the mucoadhesive property(ies) and / or anchoring feature(s) that allow the device to adhere to the surface of the eye.

[0112] In some embodiments, the device flips from having a flat or concave anterior surface and a flat or convex posterior surface to the opposite state, e.g., when the device is placed on the eye. For example, in some embodiments, a user places the device on their finger and / or an applicator (and / or the device is provided on the applicator) so that the posterior surface is convex and the anterior surface is concave. Upon attachment, e.g., before and / or while the device is in contact with the surface of the eye, a force is applied (e.g., by the user and / or the applicator), causing the device to flip to a configuration with a concave posterior surface and a convex anterior surface. In some embodiments, the device is provided pre-formed to a desired shape (e.g., including a desired curvature) for the intended insertion location. In some embodiments, the device has a curvature (e.g., is provided with a curvature) for the intended insertion location (e.g., the posterior surface of the device has a curvature for the intended insertion location). In some embodiments, the device changes shape (e.g., curvature(s)) during and / or after placement on the surface of the eye. For example, in some embodiments, the device changes shape during hydration and / or attachment, eg, to the surface of the eye.

[0113] In some embodiments, the ophthalmic device has one or more of flexibility, resilience, and flexibility, e.g., to conform to the shape of the eye. In some embodiments, the resilience and / or flexibility of the ophthalmic device is similar to that of a soft contact lens. In some embodiments, the ophthalmic device has a resilience or flexibility in one or more directions with a Young's modulus of 0.3-1.5 MPa, or 0.3-1.5 MPa, or a lower, higher, or intermediate resilience / flexibility or range. In some embodiments, the ophthalmic device has a resilience in one or more directions with a Young's modulus of 0.1-200 MPa. In some embodiments, the ophthalmic device has a resilience in one or more directions in a dry state (e.g., a Young's modulus of 0.1-200 MPa, or 0.4-1.4 MPa, or 0.3-1.5 MPa, or a lower, higher, or intermediate resilience or range). In some embodiments, the ophthalmic device has a resilience in one or more directions (e.g., a Young's modulus of 0.1-200 MPa, or 0.3-1.5 MPa, or 0.4-1.4 MPa, or a lower, higher, or intermediate resilience or range) in a wet state while in the eye. In some embodiments, the ophthalmic device has a resilience that allows for elongation (dry and / or wet) of 10% to 500% or more.

[0114] In some embodiments, the ophthalmic device has one or more of a rigidity and a fixed shape, e.g., shaped to conform to the shape of the eye. In some embodiments, the elasticity and / or stiffness of the ophthalmic device in one or more directions is similar to the elasticity and / or stiffness of a hard or rigid contact lens. In some embodiments, the ophthalmic device has an elasticity in one or more directions with a Young's modulus of 100-5000 MPa, or lower, or higher, or an intermediate range or elasticity. In some embodiments, the ophthalmic device has this elasticity in one or more directions when in a dry state. In some embodiments, the ophthalmic device has this elasticity in a wet state, e.g., while residing within the eye.

[0115] In some embodiments, an ophthalmic device comprises layers having different material properties, e.g., elasticity and / or flexibility. In some embodiments, an ophthalmic device comprises regions having different material properties, e.g., elasticity and / or flexibility.

[0116] In some embodiments, the device is flexible, potentially allowing the device to conform to the surface of the eye, for example, potentially increasing user comfort (e.g., allowing the eyelid to move smoothly over the device with little or no hindrance and / or discomfort) and / or reducing removal forces experienced by the device. In some embodiments, the flexible device has a concave posterior surface, and suction forces between the device and the surface of the eye (e.g., associated with the interaction of the concave posterior surface with the surface of the eye) cause the device to adhere to the surface of the eye. Potential advantages of a flatter (e.g., lower profile) device include, for example, reduced likelihood of dislodging with blinking and / or eye movement and / or increased wearing comfort for the subject.

[0117] In some embodiments, the resilience of the device increases the suction between the device and the surface of the eye, adhering the device to the eye, for example, in some embodiments, the resilience compensates for the low concave curvature of the posterior surface of the device.

[0118] In some embodiments, the flexibility and / or resilience of the device improves the seal between the edges of the device and the surface of the eye.

[0119] In some embodiments, the posterior surface comprises one or more mucoadhesive portions, where the mucoadhesive material(s) in some embodiments enhance adhesion of the device to the ocular surface.

[0120] Optionally, in some embodiments, the rear surface includes a mucoadhesive layer, which in some embodiments covers the rear surface. Alternatively, in some embodiments, the mucoadhesive layer is a discontinuous surface, e.g., with hole(s) that allow for water penetration and / or drug delivery, e.g., to layers below the mucoadhesive layer. In some embodiments, the mucoadhesive layer is annular with a central opening, which allows for water penetration and / or drug delivery, e.g., to layers below the mucoadhesive layer.

[0121] The mucoadhesive layer in the device is, in some embodiments, provided in a dry and / or semi-hydrated state, such that, in some embodiments, upon application of the device to the eye, the mucoadhesive layer hydrates and becomes tacky, e.g., in less than 10 seconds, or less than 30 seconds, or less than 1 minute.

[0122] In some embodiments, the mucoadhesive layer material / compound / polymer has an adhesive strength of 80-200%, or 100-200%, or greater than 100%, where pectin, for example, is defined as having 100% adhesive strength.

[0123] In some embodiments, the mucoadhesive portion comprises at least one mucoadhesive compound, which in some embodiments is selected from the group consisting of gelatin, alginate, chitosan, amylose, collagen, sodium polyacrylate, modified starch, elastin, polyacrylic acid, and combinations thereof.

[0124] In some embodiments, the rear surface of the device includes, for example, one or more cavities or protrusions.

[0125] Without wishing to be limited by theory, it is hypothesized that in some embodiments, the cavity increases suction between the device and the surface of the eye, e.g., localized suction at the cavity. In some embodiments, ocular tissue enters the cavity (e.g., under the suction of the cavity), potentially increasing adhesion between the device and the eye. A potential advantage of the cavity(ies) on the posterior surface is increased residence time of the device on the eye.

[0126] In some embodiments, the device has multiple cavities, and in some embodiments, two or more of the cavities are substantially the same size and / or shape, while in some embodiments, two or more of the cavities differ from one another, e.g., in size and / or shape.

[0127] In some embodiments, the cavity opening size is 0.005 mm to 20 mm, or 0.005 to 2 mm, or 0.005 to 1 mm, or 0.005 to 0.5 mm, or 1 to 2 mm, or smaller, or larger, or an intermediate range or dimension. In some embodiments, the cavity has a large opening, e.g., extending across at least half of the area of ​​the surface (e.g., the rear surface) and / or having a size of 1 to 10 mm, or 1 to 8 mm, or 1 to 5 mm. In some embodiments, the cavity opening is macroscopic or microscopic in size. In some embodiments, the cavity depth is 5 microns to 1 mm, or 5 to 400 microns, or 5 to 200 microns, or shallower, or deeper, or an intermediate depth or range. In some embodiments, the cavity extends through most of the thickness of the device, for example, at least 50-90%, or 80-99%, or 90-99%, or lower, or higher, or intermediate ranges or percentages of the thickness of the device in the cavity region.

[0128] In some embodiments, the protrusion(s) have a rounded and / or blunt shape.

[0129] In some embodiments, the device has multiple protrusions, and in some embodiments, two or more of the protrusions are substantially the same size and / or shape, while in some embodiments, two or more of the protrusions differ from one another, for example, in size and / or shape.

[0130] In some embodiments, the size of the protrusions above the surface of the device is 5 to 400 microns, or 20 to 200 microns, or smaller, or larger, or an intermediate range or size. In some embodiments, the footprint size of the protrusions on the surface of the device is 5 microns to 3 mm, or 5 microns to 1 mm, or 5 to 700 microns, or 5 to 400 microns, or smaller, or larger, or an intermediate size or range.

[0131] A potential benefit of the protrusion(s) is increased adhesion of the ocular device to the ocular surface. In some embodiments, the protrusion(s) increase friction between the ocular surface and the posterior surface of the device. In some embodiments, increased protrusion(s) increases the suction force between the device and the ocular surface (e.g., between the protrusions).

[0132] In some embodiments, the device presents a low friction surface against the eyelid (e.g., is smooth), the potential advantage of which is that it reduces the likelihood of the device becoming dislodged.

[0133] Optionally, in some embodiments, one or more portions of the front surface of the device are lubricious and / or comprise a lubricious material, where the front surface of the device is the surface that contacts the inner surface of the eyelid at least part of the time. Potentially, in some embodiments, the lubricity and / or lubricity reduces friction between the eyelid and the front surface. Potentially, in some embodiments, the lubricity and / or lubricity minimizes irritation to the eye, e.g., eyelid, associated with ophthalmic devices.

[0134] In some embodiments, a lubricious material layer covers the front surface, and in some embodiments, the layer is continuous. In some embodiments, the lubricious layer is a discontinuous surface (e.g., contains one or more holes), which allows, for example, water penetration and / or drug delivery. For example, in some embodiments, the lubricious material layer contains holes. In some embodiments, the front surface carries one or more lubricious material portions, and in some embodiments, one or more of the portions are connected to other portion(s) and / or one or more of the portions are not connected to other portions. Optionally, in some embodiments, the lubricious surface is temporary, and in some embodiments, one or more portions of the lubricious material degrade and / or disappear (e.g., are absorbed and / or excreted by the eye), e.g., before other portion(s) of the device degrade.

[0135] In some embodiments, the material layer has variable thickness and / or variable material properties, such as, for example, a lubricious layer and / or a mucoadhesive layer, such that, for example, the material has a greater extent at its front surface when attached to the eye than after a period of residence on the eye, and in some embodiments, the more rapidly degrading portion(s) of the layer (e.g., thinner portions and / or portions having a more rapidly degrading composition) dissolve before other portion(s), e.g., in some embodiments, exposing an underlying layer containing the therapeutic agent(s).

[0136] In some embodiments, the device has edges designed for user comfort and / or to enhance adhesion to the eye. In some embodiments, the ophthalmic device has thin edges. In some embodiments, the edges (e.g., peripheral edges) of the device have an average thickness of about 15 microns, or about 20 microns, or about 30 microns, or about 50 microns. In some embodiments, the ophthalmic device has thin edges of about 15 microns or about 20 microns. In some embodiments, the ophthalmic device has an edge thickness of about 5-200 microns, or 5-200 microns, or thinner, or thicker, or an intermediate thickness or range. In some embodiments, the edges of the device are, for example, blunt and / or curved and / or rounded, which improves user wearing comfort. In some embodiments, the edges of the device are sharp, for example, chisel-shaped and / or knife-edge-shaped. In some embodiments, the edges of the ophthalmic device are defined by an edge region of the device of 0.1-1 mm, or 0.5-1 mm. In some embodiments, the edge thickness is measured 0.5 mm or 1 mm from the perimeter of the device.

[0137] In some embodiments, thin edges potentially reduce the likelihood of the device becoming dislodged, for example, during blinking and / or eye movement, because a device with a thin edge has a smaller surface area that interacts with the eyelid as the eyelid moves over the area of ​​the ocular device.

[0138] In some embodiments, devices with thin edges provide an improved seal between the edge of the device and the surface of the eye. A potential benefit of a seal between the edge of the device and the surface of the eye is increased suction between the device and the surface of the eye. A potential benefit of a seal between the edge of the device and the surface of the eye is reduced accumulation of debris (e.g., accumulation of one or more of proteins, mucus, oils, and skin cells) between the device and the surface of the eye, potentially minimizing the risk of infection associated with the use of ophthalmic devices.

[0139] In some embodiments, the thin edge of the device conforms to the shape of the surface of the eye at the edge of the device.

[0140] In some embodiments, the edges of the device secure the device to the surface of the eye, e.g., the soft tissue of the conjunctiva, e.g., the soft, thick scleral conjunctiva, which has an appearance of about 25-40 microns thick and an appearance of greater thickness at the fornix. In some embodiments, the device digs into the surface of the eye with the edges of the device and / or creates a depression in the surface of the eye, e.g., digging occurs due to one or more of pressure between the edges of the device and / or softness of the surface of the eye.

[0141] In some embodiments, the edge (and / or edge region(s)) of the device conforms to the shape of the surface of the eye. For example, in some embodiments, the edge region(s) are flexible and / or resilient and / or sufficiently thin to conform to the surface of the eye. Potentially, the conforming edge to the surface of the eye reduces the risk of the device becoming dislodged. In some embodiments, the ophthalmic device is thin and / or low profile, e.g., the maximum thickness of the device and / or the thickness of the device is 40-200 microns, or 120-300 microns, or 200-1000 microns, or 300-500 microns, or about 400 microns, or up to 400 microns, or up to 300 microns, or about 200 microns, or up to 200 microns, or up to 150 microns, or up to 100 microns, or up to 80 microns, or up to 60 microns, or thinner, or thicker, or an intermediate range or thickness. Potential advantages of a thinner device include one or more of: increased flexibility of the device, less irritation to the eye, less likelihood of migration, and / or less likelihood of excretion from the eye.

[0142] In some embodiments, the thickness of the ophthalmic device is less than 100 microns, or 200 microns or less, or 60 microns or less, or 40 microns or less, or 80-100 microns, or 60-80 microns, or 40-60 microns, or 20-40 microns, or 10-20 microns, or 5-10 microns, or 10 microns or less, or 5 microns or less.

[0143] In some embodiments, the pressure between the eye and the device is increased by increasing the thickness of the device and / or the thickness of the edge regions of the device, and the increased pressure (and / or the resulting seal between the eye and the device, e.g., and / or contouring of the eye to the device or contouring of the device to the eye) in some embodiments reduces tear penetration between the device and the surface of the eye.

[0144] In some embodiments, the device is small. In some embodiments, the maximum dimension and / or average dimension of the device is about 1-8 mm, or 4-6 mm, or smaller, or larger, or any intermediate range or size. In some embodiments, the ophthalmic device is 4 mm in size (e.g., maximum dimension and / or average dimension). In other embodiments, the device has a dimension of about 0.5 to about 20 mm at its maximum dimension. A potential advantage of a device with small dimensions is that it is less likely to fall off while the eyelid moves over the device.

[0145] In some embodiments, the ophthalmic device is elongated, for example, in some embodiments, the dimension of the device measured along the axis of elongation is about 0.5 mm, or about 1 mm, or about 2 mm, or about 3 mm, or about 4 mm, or about 5 mm, or about 6 mm, or about 7 mm, or about 8 mm, or about 9 mm, or about 10 mm, or about 11 mm, or about 12 mm, or about 13 mm, or about 14 mm, or about 15 mm, or about 16 mm, or about 17 mm, or about 18 mm, or about 19 mm, or about 20 mm.

[0146] In this regard, in some embodiments, the size of the device is measured by the largest dimension of the smallest rectangular shape the device can fit into. In some embodiments, for example, because the device surface has a low curvature, the rectangular bounding shape is thinner in one dimension (e.g., the dimension associated with the direction toward the eye when the device is on the eye) than in the other two dimensions.

[0147] An aspect of some embodiments of the present invention relates to ophthalmic devices that degrade and / or disintegrate in the eye.

[0148] In some embodiments, the ophthalmic device is a biocompatible device designed to be partially or completely biodegradable and / or bioerodible.

[0149] For example, in some embodiments, a portion of the device degrades, e.g., upon attachment of the device to the ocular surface. For example, one or more mucoadhesive portions and / or one or more lubricious portions degrade. For example, in some embodiments, one or more portions of the device are selected to degrade in the eye within about 1 minute to 30 minutes, or 15 minutes to 1 hour, or about 0.5 hours to 8 hours, or 4 hours to 24 hours, or 12 hours to 3 days, or 1 day to 7 days, or 3 days to 2 weeks, or 1 week to 1 month. In some embodiments, degradation of one or more portions allows for elution of a therapeutic substance. For example, in some embodiments, degradation of a portion containing a therapeutic substance allows elution of the therapeutic substance into ocular tissues and / or ocular fluids. For example, in some embodiments, degradation of a portion reveals a portion containing a therapeutic substance. At this time, in some embodiments, the degraded portion initially covers at least a portion of the portion containing a therapeutic substance.

[0150] In some embodiments, the device includes a biodegradable and / or bioerodible material and / or the device body is biodegradable and / or bioerodible. For example, in some embodiments, the material and / or device degrades and / or its properties deteriorate when exposed to a biological environment, such as a biological system, e.g., an eye, and / or when exposed to a similar ex vivo environment that simulates the conditions of a biological system. In some embodiments, the degradation and / or deterioration of the device is manifested by a change (e.g., a decrease) in one or more of the physical properties of the device, such as the integrity of the device, the tensile strength, and / or elasticity of the device body (e.g., a film on the device body).

[0151] One aspect of some embodiments of the present invention relates to a multi-layered ophthalmic device. In some embodiments, the device comprises one or more of a lubricating layer, a mucoadhesive layer, and an additional layer. In some embodiments, one or more layers comprise a therapeutic substance. In some embodiments, the additional layer is disposed between the mucoadhesive layer and the lubricating layer, forming an intermediate layer. In some embodiments, the device comprises three or more layers, or four or more layers, e.g., 1 to 10 layers, or fewer, more, or an intermediate number or range of layers. In some embodiments, one or more layers extend over the surface of the device. In some embodiments, one or more layers do not cover the surface of the device, e.g., cover a portion of the area of ​​the device surface, e.g., have holes. In some embodiments, the intermediate layer covers a portion (e.g., half) of the device, and in some embodiments, the portion of the device including the intermediate layer is positioned below the surface of the eye.

[0152] In some embodiments of the invention, the device is made of a film comprising at least two layers. In some embodiments, the film is made of a combination of biodegradable materials and / or materials that form the raw material of the device of the invention; e.g., in some embodiments, the film is manufactured into a device by one or more processing steps.

[0153] In some embodiments, the therapeutic agent(s) are released from the device (e.g., from an interior surface and / or portion of the device) through pores, holes, apertures, and / or channels. In some embodiments, the therapeutic agent(s) are released from the device through one or more of the rear surface (or portion thereof), the front surface (or portion thereof), the periphery and / or edge (or portion thereof) of the device. For example, through one or more of the pores, holes, apertures, and channels. In this regard, in some embodiments, the pores and / or holes and / or apertures and / or channels are millimeter, submillimeter, or nanometer in size.

[0154] A potential advantage of ophthalmic devices is their convenience of use, and in some embodiments, the devices, once applied by the user, accommodate longer periods of time than topical formulations, e.g., greater than 10 minutes, or greater than 1 hour, or greater than 1 day, where in some embodiments the device acts as a means for controlled release of one or more therapeutic components.

[0155] A potential advantage of ophthalmic devices configured to remain on the surface of the eye is the potentially longer residence time of the therapeutic agent within the eye, for example, compared to topical therapeutic agents (e.g., eye drops, ointments) that are administered periodically.

[0156] A potential advantage of ophthalmic devices that release drugs while remaining on the ocular surface is that they may provide and / or maintain adequate concentrations of drug in the precorneal / prescleral tear film, for example, for a longer period of time.

[0157] A potential advantage of ophthalmic devices that elute a drug while remaining at the surface of the eye, for example, while maintaining a position on the surface of the eye, is that they potentially allow diffusion of the drug through ocular tissues, for example, potentially into the sclera, and / or cornea, and / or into the eyeball, and / or to reach more internal portions of the eye(s), potentially allowing in some embodiments localized drug delivery to those areas that are typically treated by injection, such as, for example, into the eyeball.

[0158] A potential advantage of an ophthalmic device (e.g., an ophthalmic device with increased residence time and / or elution time) is the ability to provide and / or maintain appropriate concentrations of drug to the intranasal region(s) (e.g., tear delivery), and / or to the brain, and / or to the head, and / or to another target organ, and / or for systemic drug delivery.

[0159] In some embodiments, the ophthalmic device's dwell time allows for a steady release of the therapeutic substance into the eye, potentially reducing the impact of periodic administration, e.g., after a temporary period of systemic and / or local overdosing (which may have a high risk of side effects), allowing for an extended period of subtherapeutic levels before administering the next dose. In this case, the tissue drug uptake rate is initially high after administration but rapidly declines. The longer dwell time is compared to eye drops administered to the eye, e.g., the surface of the eye, where blinking and natural tearing combine to limit the duration of time the liquid medication remains effective, e.g., to a few minutes. Potentially, when treating a subject using an ophthalmic device, less therapeutic component is used per treatment, as opposed to, e.g., topical formulations, which require larger amounts of the therapeutic component because the therapeutic component may be washed away before it becomes effective, and / or more frequent administration, potentially resulting in less patient compliance and potentially more waste of unused therapeutic component.

[0160] In some embodiments, the ophthalmic device contains a large amount of therapeutic component(s) (e.g., about 1 mg to about 20 mg, or greater than 1 mg, or greater than 20 mg, or smaller amounts, or larger amounts, or intermediate doses or ranges) and / or is capable of dissolving such component(s) onto the surface of the eye. A potential advantage of the ophthalmic device is that it can deliver therapeutic components (e.g., larger amounts than topical formulation(s)) to the surface of the eye and / or into the eye (potentially replacing intraocular injections). Whereas, for example, topical formulations deliver therapeutic components at concentrations up to 1% of the eye drop, e.g., 0.3 mg of therapeutic component in a 30 microliter eye drop, it is expected that the majority of the therapeutic component will be naturally washed away from the eye within minutes.

[0161] A potential advantage of an ophthalmic device that releases a large amount of drug while remaining on the surface of the eye is that it can provide and / or maintain adequate concentrations of drug in the intranasal region and / or to the brain and / or to the head and / or to another target organ, and / or provide systemic drug delivery (e.g., for medications such as "microdosing" of cannabinoids and / or opioids). In some embodiments, the device is used for recreational drug use.

[0162] An aspect of some embodiments of the present invention relates to a kit including an ophthalmic device (e.g., an ophthalmic device described herein) and instructions for use thereof. In some embodiments, the kit includes a means for delivering the device into a patient's eye, such as an applicator. In some embodiments, the ophthalmic device is packaged with the applicator.

[0163] Optionally, in some embodiments, the kit includes a degradation formulation that structurally degrades and / or accelerates degradation of the device upon contact with the device when the device is present on the surface of a patient's eye.

[0164] In some embodiments, the devices are provided in a multi-device pack, where in some embodiments, two or more devices are interconnected or separate.

[0165] In some embodiments, the ophthalmic device protects a portion of the eye. For example, it protects the portion of the eye from external impact(s) and / or chemical changes. For example, it ameliorates and / or reduces eye damage during orbiscultation (when juice from citrus fruits squirts into the eye). In some embodiments, the ophthalmic device protects a portion of the eye and allows the portion to heal. For example, in some embodiments, an incision and / or wound in the eye is closed and / or covered by placing the ophthalmic device over the incision. Suction between the surface of the eye and the device then potentially assists in and / or maintains closure of the incision and / or wound, thereby potentially speeding healing.

[0166] In some embodiments, the device is designed to provide one or more therapeutic treatment requirements, for example, in some embodiments, the biodegradability characteristic(s), residence time, and drug release time are selected to meet the therapeutic treatment requirement(s) for one or more planned locations on the surface of the eye.

[0167] In some embodiments, the device is tailored to an individual subject, e.g., in some embodiments, one or more of the size, shape, curvature of the surface(s), treatment type, release time, and residence time are selected for the individual and / or according to an individual treatment plan.

[0168] Although ophthalmic uses of the devices are described throughout this specification, it should be understood that one or more embodiments and / or combinations of embodiments of the devices described herein may, in some embodiments, be used to treat other parts of the human or animal body, such as parts of the eye other than the sclera, e.g., the cornea, the conjunctival sac of the eye, other mucosal surface(s), e.g., the interior of the mouth, e.g., the interior of the nasal cavity, or other tissue types and / or organs.

[0169] Although ophthalmic uses of devices are described throughout this specification, it should be understood that one or more embodiments and / or combinations of embodiments of the devices described herein may, in some embodiments, be used in other applications, such as to host, e.g., contain, mount, and / or provide support for, one or more types of electronic devices on the eye. For example, one or more active electronic elements, passive modules, antennas, RFID tags, and other components may be used. For example, one or more capacitors, resistors, and / or shape memory elements may function as support for other element(s), such as in the ocular region. In this regard, for example, in some embodiments, the electronic devices include one or more of the following: sensor(s) (e.g., temperature-sensitive, pressure-sensitive, moisture-sensitive), imager(s) (e.g., camera), user interface, processor, transmitter, receiver, lighting element, LED screen, and power source. In some embodiments, the electronic devices (e.g., using sensor(s)) are used for therapy (e.g., electroconvulsive therapy (ECT) treatment) and / or diagnosis. In some embodiments, one or more electronic components are used for entertainment (e.g., VR) and / or aesthetic enhancement. In some embodiments, the device is used for entertainment and / or aesthetic enhancement.

[0170] In some embodiments, multiple devices are used to treat a subject as described herein, e.g., multiple devices are present on the surface of the eye in vivo simultaneously, e.g., each device provides a specific dose, providing a greater dose than would be provided by a single attached device, and in some embodiments, multiple devices described herein are provided packaged together and / or are provided in conjunction with one another.

[0171] In some embodiments, the device comprises and / or is constructed of non-toxic and / or biocompatible materials, where in some embodiments the therapeutic agent is toxic at high concentrations, and in some embodiments the device contains less than a toxic dose overall and / or the device elutes the therapeutic agent at sub-toxic levels.

[0172] In some embodiments, one or more portions of the device include a dye and / or pigment for easy identification, for example, while in the eye, and / or during insertion and / or extraction, and / or manufacturing. In some embodiments, the dye and / or pigment is printed with one or more identifying shapes, letters, numbers, and / or bar codes. In some embodiments, one or more identifiers are embossed or engraved on the device. In some embodiments, the device includes one or more electronic identifiers, such as RFID, on or within the body of the device. In some embodiments, the dye and / or pigment of the device includes blue, red, fluorescent yellow, and / or any other color.

[0173] One aspect of some embodiments of the present invention relates to the manufacture of ophthalmic devices. In some embodiments, the devices are fabricated from a film, e.g., a multilayer film. In some embodiments, the film is cut into shapes to form individual devices. In some embodiments, the film and / or individual devices are shaped, e.g., to form a surface of a desired curvature. In some embodiments, shaping is achieved by casting a solution onto a shaped support surface. In some embodiments, shaping is achieved by mechanical and / or chemical processes, e.g., by applying pressure and / or heat. In some embodiments, the therapeutic components are contained in one or more solutions, and each of the solutions is cast sequentially onto the support surface to form a multilayer film. In some embodiments, the separately cast layers have one or more different properties (e.g., thickness, mucoadhesion, lubricity, therapeutic agent(s) contained therein). In some embodiments, one or more surfaces are treated to have different properties, e.g., one surface is treated to have more adhesive properties and / or more lubricity.

[0174] Before describing at least one embodiment of the present 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 components and / or methods set forth in the following description and / or illustrated in the drawings and / or examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0175] Exemplary Ophthalmic Devices FIG. 1A is a simplified schematic cross-sectional view of an ophthalmic device 100 in place on an eye surface 104, according to some embodiments of the present invention.

[0176] In this regard, in some embodiments, the ocular surface 104 is part of the conjunctival surface around the eyeball 108 .

[0177] In some embodiments, the ophthalmic device 100 resides in the bulbar conjunctiva 104 portion of the sclera, the area of ​​the conjunctiva proximal to the cornea, and between the forniceal conjunctiva 140 and the cornea 102 .

[0178] In some embodiments, at least a portion of the device 100 resides on the limbus 142 .

[0179] In some embodiments, at least a portion of device 100 is positioned adjacent to the meniscus 105 (the groove between the eyelid edge and the eyeball where tears / tear fluid accumulate and form a reservoir).

[0180] In some embodiments, at least a portion of device 100 or all of device 100 resides in another portion of the conjunctiva, which includes, for example, one or more features described in and / or with respect to step 302 of FIG. 3 and / or in the "Overview" section of this specification.

[0181] In some embodiments, Figure 1A shows the device 100 on the lower eyelid 106. In some embodiments, Figure 1A shows the device 100 on the upper eyelid 106.

[0182] In some embodiments, device 100 has a body including a rear surface 116 and a front surface 118. In some embodiments, rear surface 116 is concave and / or front surface 118 is convex. In some embodiments, rear surface 116 and / or front surface 118 include one or more features described and / or illustrated with respect to one or more of surfaces 416, 417, 418, 419 in FIG. 4 and / or with respect to one or more of the rear and / or front surfaces illustrated and / or described in one or more of FIGS. 5, 18-31C, 38-58, and / or other exemplary devices described elsewhere herein.

[0183] FIG. 1B is a simplified schematic top view of an ophthalmic device 100 in place on an eye surface 104, according to some embodiments of the present invention.

[0184] In some embodiments, device 100 is symmetrical in shape. In some embodiments, device 100 has a circular footprint, for example, when resting on the surface 104 of the eye. In some embodiments, the size 103 of device 100 is the diameter 103 of device 100. In some embodiments, device 100 has an alternative shape and / or footprint, including, for example, one or more features described and / or illustrated with respect to one or more of devices 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 of Figures 8-17.

[0185] 1C-1D are simplified diagrams of an ophthalmic device 100 in place on an eye, according to some embodiments of the present invention.

[0186] Figure 1C shows that in some embodiments, when device 100 is in place on the scleral surface of the eye, in some embodiments, the device is partially and / or fully exposed by the eyelid when the eye is in a relaxed, open position. Figure 1D shows that in some embodiments, the lower eyelid is manually pulled down to expose device 100.

[0187] Although Figures 1C-1D show device 100 in place below the sclera, it should be understood that in some embodiments, device 100 is placed above and / or resides above the sclera.

[0188] Exemplary Methods FIG. 2 illustrates a method of use of an ophthalmic device according to some embodiments of the present invention.

[0189] At 200, in some embodiments, the ophthalmic device is placed in the eye, for example, on the surface of the eye, for example, on a portion of the sclera.

[0190] At 202, in some embodiments, the ophthalmic device elutes a drug into the eye.

[0191] At 204, in some embodiments, the ocular device is removed from the eye.

[0192] FIG. 3 illustrates a method of use of an ophthalmic device according to some embodiments of the present invention.

[0193] At 300, in some embodiments, a substance is optionally added to the eye and / or the ophthalmic device.

[0194] For example, in some embodiments, the device is stored dry or partially hydrated and hydrated prior to use (e.g., prior to insertion into the eye). For example, hydration is achieved by adding water and / or a hydration solution to the device prior to placement on the surface of the eye. In some embodiments, the device is immersed in a hydration solution, e.g., for 5 seconds to 20 minutes, prior to placement on the eye. In some embodiments, the device is humidified by exposure to humid air and / or gas, e.g., for 1 minute to 2 hours, prior to placement on the eye.

[0195] In some embodiments, one or more therapeutic substances are applied to the device, which may include, for example, one or more of the features shown in and / or described with respect to Figures 74A-74C.

[0196] In some embodiments, mucoadhesive and / or lubricious materials are added to the device, eg, to one or more portions of the device.

[0197] At 302, in some embodiments, an ocular device is applied to the surface of the eye. Prior to application, the device is in some embodiments dry, wet, or partially hydrated (humidified). In some embodiments, applying includes contacting the device with the surface of the eye, for example, the sclera.

[0198] In some embodiments, the ophthalmic device is applied to a surface of the eye, e.g., the sclera, e.g., the bulbar conjunctiva, by contacting the device with the surface. In some embodiments, pressure is applied to the device during attachment, e.g., sufficient pressure to deform one or both of the conjunctiva and the device. For example, in some embodiments, the applied pressure deforms the conjunctiva in contact with the edges of the device and / or deforms the central region of the device, e.g., changing the curvature of one or more surfaces in the central region of the device.

[0199] In some embodiments, the ocular device is placed in a position where it will remain for a period of time (the period described in step 307). In some embodiments, the ocular device is placed on the surface of the eye and then moved to a position where it will remain for a period of time, where the movement time is shorter than the dwell time, for example, from less than 1 second to 1 minute, or less than 30 minutes, or shorter, or longer, or any intermediate range or duration.

[0200] In some embodiments, the shape and / or curvature of the surface(s) of the device (e.g., relative to the eye) guides the device to move to a desired location. For example, when the device is placed outside a desired area of ​​the eye, the device moves to the desired location and / or the device moves to the most stable position on the surface of the eye. For example, the curvature of the posterior surface of the device guides the movement of the device.

[0201] The device, in some embodiments, is inserted into the eye, and in some embodiments, the device is placed on the cornea, and / or partially on the cornea, and / or partially on the sclera, and / or on the sclera, and / or at least partially under the upper eyelid, and / or at least partially under the lower eyelid, and / or on the limbus, and / or on the fornix (e.g., in the conjunctival sac), and / or at the edge(s) of the eye, and / or on the conjunctiva.

[0202] In some embodiments, the device is applied directly and / or manually to the surface of the eye, for example, by the patient themselves. In some embodiments, the device is applied by a caregiver. Optionally, in some embodiments, the device is applied using an applicator.

[0203] In some embodiments, the ophthalmic device flips from a convex configuration to a concave configuration when applied to the surface of the eye, for example, as described elsewhere herein.

[0204] At 304, optionally, in some embodiments, the device is hydrated within the eye.

[0205] In some embodiments, the device is applied in a dry (or semi-hydrated) state, and over a period of time the device hydrates, e.g., changing its shape and / or its interaction with the ocular surface (e.g., increasing the suction force between the device and the ocular surface).

[0206] In some embodiments, the device is stored in a dry (or semi-hydrated) state and, upon insertion into the eye, the device becomes wetted by tears and / or adheres to the surface of the eye.

[0207] In some embodiments, upon hydration of the device as described with respect to steps 300 and / or 304, e.g., upon hydration by, e.g., in vivo tear fluid on the surface of the eye in step 304, the device expands and / or swells in one or more dimensions from its dry (and / or semi-hydrated) dimensions, e.g., by 10% to 50%, or more than 50% (e.g., from 100% to more than 150% of its pre-hydrated dimensions), or by lower, higher, or intermediate ranges and percentages.

[0208] In some embodiments, one or more of the layers of a multi-layer device have different swelling properties when wetted, such that hydration, in some embodiments, changes the curvature and / or thickness profile of one or more layers and / or the device body.

[0209] At 306, in some embodiments, the device adheres to the eye, e.g., the device is now sufficiently firmly attached so that during the dwell time (e.g., the dwell time described in step 307), the device does not move significantly (e.g., move by a maximum of 0.01-5 mm, or 0.1-0.2 mm, or 0.2-1 mm) and / or is not expelled from the eye.

[0210] In this regard, in some embodiments, when the device is applied to the surface of the eye (i.e., when present in vivo), the device adheres to the surface of the eye due to the material properties of the mucoadhesive layer of the device upon application and / or after the properties of the mucoadhesive layer change in vivo (e.g., hydration).

[0211] At 307, in some embodiments, the device remains on the eye for a period of time.

[0212] In some embodiments, the device is maintained in vivo (in the eye) for a period of at least 0.5 hours. In other embodiments, the device is maintained in vivo for a period of 0.1 to 2 hours, or 2 to 8 hours. In further embodiments, the device is maintained in vivo for a period of over 8 hours. In further embodiments, the device is maintained in vivo for a period of 8 to 24 hours, 1 to 7 days, 7 days to 1 month, 1 to 3 months, or 3 months to 1 year. In some embodiments, the device is maintained in vivo for about 1 day to about 30 days, or 1 month to 1 year.

[0213] In some embodiments, the device remains and / or remains in vivo (residence time) and is drained and / or removed from the eye in less than about 24 hours from administration, at which time drainage and / or removal, in some embodiments, leaves the eye clean and free of devices (e.g., debris), e.g., the eye is ready for administration of additional devices, etc.

[0214] At 308, optionally, in some embodiments, one or more portions of the device degrade and / or disintegrate, for example, where the degrade and / or disintegrate comprises one or more features shown in and / or with respect to one or more of Figures 62A-62E, 63, 64A-64C, 65A-65D, and 66.

[0215] In some embodiments, the device has one or more regions and / or portions that dissolve rapidly (e.g., in less than 1 minute, or less than 10 minutes, or less than 1 hour) after insertion. These region(s) in some embodiments facilitate insertion or placement of the device into the eye. For example, handles and / or protrusions are used to manipulate the eye during attachment and / or insertion. These region(s) in some embodiments cover the pupil area (e.g., the region(s) cover the patient's line of sight).

[0216] In some embodiments, degradation of the device occurs through one or more of mechanical degradation (such as eyeball or eyelid movement), chemical degradation (such as tears), or biological degradation (such as enzymatic activity).

[0217] At 310, in some embodiments, the device performs a therapy, such as eluting a drug into the eye. In some embodiments, elution involves the degradation of an eluting portion of the device.

[0218] At 312, optionally, in some embodiments, one or more portions of the device collapse. For example, a portion of the device collapses to reveal the therapeutic substance and / or additional therapeutic substance. In some embodiments, a portion(s) of the device participate in the adhesive collapse of the device, including, for example, a mucoadhesive layer, or portions that contribute to mechanical adhesion, such as portion(s) at the edge of the device and / or portion(s) that alter the curvature of one or more surfaces of the device.

[0219] At 314, optionally, in some embodiments, the device disintegrates, e.g., by mechanically reducing the device's adherence to the eye and / or reducing the size of the device and / or breaking the device apart. In some embodiments, the entire device disintegrates after a residence time on the surface of the eye ranging from about 0.1 hours to 1 year.

[0220] At 316, in some embodiments, the device is naturally expelled from the eye, e.g., by eyelid and / or eyeball movement and / or blinking and / or tearing. In some embodiments, expulsion occurs, e.g., by rubbing the eyelid with a finger. In some embodiments, portions of the device are expelled (e.g., when step 314 occurs). In some embodiments, the device is naturally expelled, e.g., if portions of the device remain. For example, the device is naturally expelled when adhesion to portion(s) of the device deteriorates, as described in step 312.

[0221] At 318, optionally, in some embodiments, the portion(s) of the device are removed, for example, manually, by applying mechanical force, such as pinching and / or applying suction and / or using a removal device (e.g., suction cup, tweezers), and / or by flushing the eye. For example, removing the device is accomplished using one or more features of the device, such as, for example, slits, protrusions, etc.

[0222] In some embodiments, one or more additional treatment modalities are administered concomitantly, sequentially, or simultaneously with and / or during one or more of the described method steps 300-318. For example, in some embodiments, a topical agent is administered, e.g., during the dwell time of the device on the surface of the eye.

[0223] Exemplary Ophthalmic Device Characteristics FIG. 4 is a simplified schematic cross-sectional view of ophthalmic devices 400, 401 on the surface of an eye 404, according to some embodiments of the present invention.

[0224] In some embodiments, the ocular surface 404 is the sclera of the eye (including, for example, the conjunctiva).

[0225] In FIG. 4, the radius of curvature RS of the sclera 404 and the radius of curvature RC of the cornea 402 are shown.

[0226] In some embodiments, devices 400, 401 are not shown to scale with respect to the anatomy of the eye, whereby in some embodiments device 400 has an anterior surface 418 and a posterior surface 416. Whereby in some embodiments device 401 has an anterior surface 419 and a posterior surface 417.

[0227] In some embodiments, device 400 is the device immediately after application of the device to the sclera 404. In some embodiments, device 401 is the same device as device 400, but after a period of time has passed since application of the device to the ocular surface 404.

[0228] In some embodiments, device 400 represents the device before application, and device 401 represents the same device after application, where applying the device includes applying pressure to the device, e.g., sufficient pressure to deform the device and / or ocular tissue.

[0229] In some embodiments, after application pressure initially deforms one or both of the tissue and the device, the device, in some embodiments, reaches equilibrium between the elasticity of the device and the elasticity of the ocular surface without, for example, at least partially, deforming, at which point deformation of the device and / or tissue surface, in some embodiments, is further influenced by surface tension.

[0230] In some embodiments, deformation of the device after attachment (e.g., due to pressure during attachment or in a state where there is not enough pressure to deform the device or tissue) is caused by surface tension(s) (e.g., solely caused by surface tension(s)).

[0231] In some embodiments, due to the pressure at the edge(s) of the devices 400, 401, the edge of the device penetrates into the tissue of the eye 420 and / or a depression is created in the tissue 420. At this time, in some embodiments, the pressure at the device edge(s) is accompanied by one or more of the suction force between the device 401 and the sclera 404 and the force of eyelid movement at the front surface 419.

[0232] In some embodiments, the device 400 shows the shape of the device before contacting the eyeball (e.g., including the radii of curvature of the front and rear surfaces of the device). In some embodiments, the device 401 shows the shape of the device after contacting the eyeball.

[0233] In some embodiments, due to the force(s) (e.g., suction and / or force(s) externally applied by the user and / or applicator) between the device 400 and the sclera 404 (and / or the applied force), the device becomes flat, for example, a transition between the device 400 and the device 401 occurs. At this time, in some embodiments, due to the force, one or more of the following occur: an increase in the radius of curvature of the rear surface (e.g., radius RP < RP1), an increase in the radius of curvature of the front surface (e.g., RA < RA1), and an increase in the size of the device.

[0234] In some embodiments, the front surface 418 has a radius of curvature RA that is smaller than the radius of curvature RP of the rear surface. At this time, for example, in some embodiments, RP is 1.2 to 5 times, or smaller, or larger, or an intermediate multiple or range of RA.

[0235] In some embodiments, these dimensions and / or ratios (e.g., curvatures) described herein relate to the curvature of an average adult eye, where, for example, in some embodiments, RS is about 12 mm and RC is about 8 mm. In some embodiments, dimensions are selected for different anatomical structures, such as a child's eye, an animal's eye, or for other surfaces (e.g., mucosal surfaces).

[0236] In some embodiments, flattening the device increases the size of the device. In this regard, in some embodiments, the size of the device is defined as the maximum and / or average dimension of the smallest rectangular shape that contains the device. In some embodiments, for devices with a circular footprint, the size of the device is the diameter of the device. In this regard, in some embodiments, the footprint is defined by the shape of the edges of the portion of the device that contacts the surface when placed on a surface (e.g., a flat surface such as the surface of an eye).

[0237] In some embodiments, flattening the device reduces the thickness of device thicknesses 424, 425. For example, in some embodiments, thickness 424 > thickness 425.

[0238] In some embodiments, the device is flattened without breaking. In some embodiments, the device has one or more of flexibility, elasticity, and ductility.

[0239] In some embodiments, the elongation at break of the device in a wet state (eg, a hydrated device and / or a semi-hydrated device) is from about 10% to about 400% elongation.

[0240] In some embodiments, the portion(s) of the eye are deformed (e.g., by the device) in depth, e.g., at the edges of the device (and / or in the areas(s) adjacent to the protrusions and / or cavities of the device described elsewhere herein, e.g., with respect to Figures 30A-30C), by 50 microns to 500 microns, or smaller, or larger, or intermediate dimensions or ranges.

[0241] In some embodiments, the deformation of the eye is localized, e.g., up to 3 mm of the surface area of ​​the eye. 2 or 1mm 2 spanning.

[0242] In some embodiments, the central region of device 400, 401 deforms upon and / or during application of the device to the eye. For example, the central 50-95% of the volume and / or area of ​​one or more surfaces deforms. In some embodiments, the deformation of the central region of the device occurs due to a change in curvature of one or more surfaces, e.g., this includes one or more of the features described with respect to the change in surface curvature from device 400 to device 401.

[0243] In this regard, in some embodiments, the variation in radius of curvature of the central region of the device on the posterior and / or anterior surface varies from 0.5 to 3 mm, or shorter, or longer, or any intermediate range or length.

[0244] In some embodiments, the local tissue at the edge of the device deforms, for example, an area of ​​tissue at the edge of the device by up to 0.5 mm, or 1 mm, or a shorter, longer, or intermediate tissue width.

[0245] In some embodiments, the maximum space 498, 499 between the device 400, 401 and the ocular surface depends on one or more of the size and / or curvature of the proximal surface of the device 400, 401 and / or the curvature of the ocular surface adjacent to the proximal surface. In some embodiments, the dimension(s) of the space depend on the flexibility of the device and / or the suction force between the device and the ocular surface.

[0246] In some embodiments, exemplary maximum space dimensions for different device sizes, before the device is placed on and / or attached to the ocular surface 404, as shown, for example, by device 400, are shown in the table below. These dimensions, in some embodiments, correspond to a posterior radius of curvature of about 9.6 mm and an ocular surface radius of curvature of about 12 mm. For example, in some embodiments, a device having a size (e.g., diameter) of 2-8 mm has a maximum space of 10-190 microns, e.g., about 50 microns. [Table 1]

[0247] In some embodiments, for example, upon transition of device 400 to device 401, the space between the posterior surface and the surface of the eye is reduced, for example, by 10-90%, or by a lower, higher, or intermediate range or percentage.

[0248] In some embodiments, the radius of curvature of a surface (and / or edge and / or corner) is defined as the radius of a circle (e.g., as shown by the dashed circle in FIG. 4 ), which corresponds to at least 60%, 80%, or 90% of the curvature of the surface (and / or edge and / or corner). In some embodiments, the device has different radii of curvature for different cross-sections of the device. In some embodiments, the device has different curvatures for different cross-sections, but one or more or all of the curvatures are described in the context described herein. In some embodiments, the posterior surface, for example, has different radii of curvature for different cross-sections, and the ratio of each of these radii to the radius of curvature of the sclera is greater than 0.8. In some other embodiments, the device has a volume of about 1 nanoliter to about 20 microliters.In some embodiments, the volume of the device is about 1 nanoliter, or about 2 nanoliters, or about 3 nanoliters, or about 4 nanoliters, or about 5 nanoliters, or about 6 nanoliters, or about 7 nanoliters, or about 8 nanoliters, or about 9 nanoliters, or about 10 nanoliters, or about 11 nanoliters, or about 12 nanoliters, or about 13 nanoliters, or about 14 nanoliters, or about 15 nanoliters, or about 20 nanoliters, or about 30 nanoliters, or about 40 nanoliters, or about 50 nanoliters, or about 60 nanoliters, or about 70 nanoliters, or about 80 nanoliters, or about 90 nanoliters, or about 100 nanoliters, or about 200 nanoliters, or about 300 nanoliters, or about 400 nanoliters, or about 500 nanoliters, or about 600 nanoliters, or about 700 nanoliters, or about 800 nanoliters, or about 900 nanoliters, or about 1 microliter, or about 2 microliters, or about 3 microliters, or about 4 microliters, or about 5 microliters, or about 6 microliters, or about 7 microliters, or about 8 microliters, or about 9 microliters, or about 10 microliters, or about 12 microliters, or about 14 microliters, or about 16 microliters, or about 18 microliters, or about 20 microliters.

[0249] In some embodiments, the device has a mass of about 1 microgram to about 20 milligrams, hi some embodiments, the mass of the device is about 1 nanogram, or about 2 nanograms, or about 3 nanograms, or about 4 nanograms, or about 5 nanograms, or about 6 nanograms, or about 7 nanograms, or about 8 nanograms, or about 9 nanograms, or about 10 nanograms, or about 11 nanograms, or about 12 nanograms, or about 13 nanograms, or about 14 nanograms, or about 15 nanograms, or about 20 nanograms, or about 30 nanograms, or about 40 nanograms, or about 50 nanograms, or about 60 nanograms, or about 70 nanograms, or about 80 nanograms, or about 90 nanograms, or about 100 nanograms, or is about 200 nanograms, or about 300 nanograms, or about 400 nanograms, or about 500 nanograms, or about 600 nanograms, or about 700 nanograms, or about 800 nanograms, or about 900 nanograms, or about 1 milligram, or about 2 milligrams, or about 3 milligrams, or about 4 milligrams, or about 5 milligrams, or about 6 milligrams, or about 7 milligrams, or about 8 milligrams, or about 9 milligrams, or about 10 milligrams, or about 12 milligrams, or about 14 milligrams, or about 16 milligrams, or about 18 milligrams, or about 20 milligrams, or about 40 milligrams, or about 100 milligrams.

[0250] Exemplary Ophthalmic Device Shapes FIG. 5A is a simplified schematic top view of an ophthalmic device 500, according to some embodiments of the present invention.

[0251] FIG. 5B is a simplified schematic side view of an ophthalmic device 500, according to some embodiments of the present invention.

[0252] FIG. 5C is a simplified schematic cross-sectional view of an ophthalmic device 500, according to some embodiments of the present invention.

[0253] FIG. 5D is a simplified schematic diagram of an ophthalmic device 500, according to some embodiments of the present invention.

[0254] In some embodiments, device 500 includes one or more features shown in and / or described with respect to device 100 of FIGS. 1A-1D and / or device(s) 400, 401 of FIG.

[0255] In some embodiments, device 500 includes a front surface 518 and a rear surface 516. In some embodiments, device 500 has a thickness 542 such that a central region of device 500 is higher than an edge region(s) of device 500. In this regard, in some embodiments, the thickness tapers from a maximum dimension at an interior (e.g., center) point and / or region of the device. In this regard, thickness 542 shown in FIG. 5C is, in some embodiments, the maximum thickness of device 500. In some embodiments, the thickness of device 500 is rotationally symmetric. In this regard, for example, the cross-section shown in FIG. 5C represents the entire cross-section of the device. Alternatively, in some embodiments, the thickness profile varies across the device.

[0256] 5A , in some embodiments, the size 526 of the device 500 is the diameter of the device's circular footprint. In some embodiments, the size includes one or more features described elsewhere herein with respect to sizes. In exemplary embodiments, the size 526 is 2-8 mm, or 3-8 mm, or smaller, or larger, or an intermediate range or size.

[0257] In some embodiments, the size 526 of the device 500 is much smaller, for example, 0.1-1 mm, or 1-3 mm, or smaller, or larger, or any intermediate size or range.

[0258] FIG. 6 is a simplified schematic cross-sectional view of an edge portion 644 of an ophthalmic device, according to some embodiments of the present invention.

[0259] FIG. 7 is a simplified schematic cross-sectional view of an edge portion 744 of an ophthalmic device, according to some embodiments of the present invention.

[0260] In this regard, in some embodiments, the edge region 644, 744 of the device is 1-20% of the edge of the device body 600, 700 and / or 0.1-1 mm of the edge of the device body 600, 700.

[0261] In some embodiments, the device body 600, 700 tapers (e.g., as described elsewhere) toward the device edge region 644, 744. For example, the taper is associated with curvature of the rear surface 616, 716 and / or the front surface 618, 718 of the device.

[0262] 6 , in some embodiments, edge region 644 is “chisel” shaped. In some embodiments, at least the edge region of the device includes two edge surfaces: a first edge surface 644 and a second edge surface 646. Here, in some embodiments, first edge surface 644 slopes away from the front surface 618 of the device, e.g., toward the rear. In some embodiments, second edge surface 646 slopes away from the rear surface 616 of the device, e.g., toward the front. In some embodiments, first edge surface 644 and second edge surface 646 meet at corner 645. In some embodiments, one or both of edge surfaces 644, 646 are planar and / or have a smaller radius of curvature than front surface 618 and / or rear surface 616. In some embodiments, the angle 645 is an acute angle, e.g., having a radius of curvature less than 500 microns, or less than 1 mm, or less than 100 microns, or smaller, or larger, or intermediate, such that in some embodiments, the acute angle 645 digs into and / or creates a depression in the surface of the eye when the device is present on the surface of the eye in vivo.

[0263] 7, in some embodiments, moving along edge region 744 toward edge 746 of the device, device body 700 continues to taper toward edge 746 (e.g., the curvature of rear surface 716 and / or front surface 718 remains approximately the same at the edge portion(s) as in other portion(s) of device 700). For example, a "knife" edge is formed having a radius of curvature of less than 0.5 mm, or less than 500 microns, or less than 1 mm, or less than 100 microns, or smaller, or larger, or intermediate, etc.

[0264] In some embodiments, a single taper is created by tapering the device 700 toward the edge(s) of the device, for example, with a curvature of the front surface 718 and / or rear surface 716. Here, the taper is with the curvature of the front surface 718, as shown, for example, in FIG. 7. Alternatively, in some embodiments, the knife edge device has a double tapered edge. In some embodiments, alternatively or additionally, the taper is with the curvature of the rear surface.

[0265] The device, in some embodiments, has a polygonal three-dimensional shape (e.g., footprint shape), such as a disk, ring, oval, elongated oval, curved oval, curved elongated oval, rod, octet, triangle, square, pentagon, or hexagon.

[0266] 8-17 are simplified schematic top views of ophthalmic devices according to some embodiments of the present invention.

[0267] In some embodiments, one or more of Figures 8-17 show a footprint of a device (eg, a footprint as defined above).

[0268] In some embodiments, the ophthalmic devices of Figures 8-17 include a film that is thin relative to the dimension(s) of the device when viewed in top view and / or footprint(s) of the device, e.g., as shown in Figures 8-17, where in some embodiments, the size of the device in one or more dimensions in top view is 20-100 times, 2-50 times, 5-20 times, 10-20 times, 10-15 times, or smaller, or larger, or any intermediate range or multiple.

[0269] 8 and 16, in some embodiments, an ophthalmic device 800, 1600 includes one or more holes 822. For example, in some embodiments, the body of the device outlining the holes 822, 1622 has a closed shape (at least when viewed in top view as shown in FIGS. 8 and 16) that is defined by a ribbon of material, and in some embodiments, the shape is annular (e.g., in top view), such as the elongated annular shape shown in FIG. 8 or the circular shape shown in FIG. 16.

[0270] 9 and 10, in some embodiments, the ophthalmic devices 900, 1000 have an irregular shape.

[0271] In some embodiments, the shape of the device facilitates removal of the device, e.g., by pinching (e.g., manually and / or using a removal tool), where, for example, in some embodiments, the portion configured to fold, optionally a central region of the device (in one or more dimensions) (e.g., folding region 948 in FIG. 9 , 1048 in FIG. 10 ), is thinner and / or has a smaller footprint size, thereby facilitating folding after applying a pinching force to one or both of the larger regions on either side of the smaller footprint portion.

[0272] 11, 12 and 13, in some embodiments, the ophthalmic devices 1100, 1200, 1300 have an elongated shape in top view.

[0273] In some embodiments, the elongated shape is a rectangle 1100, 1200. In some embodiments, the corners of the rectangular device 1100, 1200 are rounded and / or blunt (e.g., the radius of curvature of the corners is less than 1 mm), potentially preventing damage to the surface of the eye.

[0274] In some embodiments, the elongated shape 1300 is oval.

[0275] In some embodiments, the elongated shape of the devices 1100, 1200, 1300 facilitates pinching and removal of the devices, with the pinching force being applied, for example, to the outer region(s) along the axis of elongation of the device.

[0276] 14-16, in some embodiments, the device shape, e.g., the device footprint, is selected for anatomical compatibility. For example, in some embodiments, devices 1400, 1500, 1600 have a shape that positions the device in contact with a portion of a patient's anatomy. For example, in some embodiments, the elongated device is curved (e.g., including one or more features of device 1400 of FIG. 14 and / or device 1500 of FIG. 15) and / or describes a curved shape (e.g., device 1600 of FIG. 16) (e.g., in some embodiments, device 1600 covers the entire limbus) to contact and / or cover at least a portion of the conjunctiva, e.g., the limbus. In some embodiments, ophthalmic devices 1400, 1500 include a curved shape in top view and / or footprint, e.g., a central longitudinal axis 1528 of the curved shape is 1-40 mm in length, or 5-20 mm in length, or shorter, longer, or any intermediate range or length.

[0277] In some embodiments, devices with dimensions greater than 5-40 mm, or 5-20 mm, or 10-20 mm, and / or curved shapes are placed under the upper eyelid, for example, because there is generally more space under the upper eyelid than under the lower eyelid.

[0278] In some embodiments, the top view shape and / or footprint of a device, such as device 1600 of FIG. 16 and device 1700 of FIG. 17, is rotationally symmetric.

[0279] 17, in some embodiments, the device has one or more corners, for example, device 1700 has three corners. In some embodiments, the corners of device 1700 (and / or the elongated shapes of FIGS. 11-15) facilitate pinching and removing the device, for example, by reducing the footprint area of ​​the device compared to a circular device, for the same potential distance to apply a pinching force.

[0280] FIG. 18A is a simplified schematic top view of an ophthalmic device 1800, according to some embodiments of the present invention.

[0281] FIG. 18B is a simplified schematic diagram of an ophthalmic device 1800, according to some embodiments of the present invention.

[0282] FIG. 18C is a simplified schematic cross-sectional view of an ophthalmic device 1800 residing on the surface of an eye 1804, according to some embodiments of the present invention.

[0283] In some embodiments, device body 1800 has a rear surface 1816 and a front surface 1818, and one or more of body 1800 and / or surfaces include one or more features shown and / or described with respect to device 100 of Figures 1A-1D and / or device 400 of Figure 4 (and / or one or more other devices described and / or shown herein).

[0284] In some embodiments, the device body 1800 includes one or more cavities 1830, 1832. In this regard, in some embodiments, the cavity(ies) 1830, 1832 are positioned on the posterior surface 1818 of the device, e.g., proximal to the surface 1804 of the eye.

[0285] In some embodiments, device 1800 includes 1-50 cavities, or 1-10 cavities, or fewer, more, or an intermediate number of cavities. In some embodiments, device 1800 has four cavities 1830, as shown, for example, in Figures 18A-18B.

[0286] In some embodiments, one or more cavities are connected and / or linked.

[0287] In some embodiments, one or more of the cavities are isolated, for example, all of the cavities are isolated from one another, as shown in Figures 18A-18B.

[0288] Exemplary cavity shapes include, for example, ball, dome, cylinder, pyramid, rectangle, triangle, circle, oval, elongated, round, ring, partial ring, radial, circumferential, and any other shape.

[0289] In some embodiments, the cavity has one or more sharp edges at the opening of the cavity, hi some embodiments, the cavity has one or more blunt and / or rounded edges at the opening of the cavity.

[0290] In some embodiments, the device comprises multiple cavities, wherein one or more of the multiple cavities has a different property(ies) than one or more other cavities.

[0291] In some embodiments, one or more cavities 1830 are open to the front surface, e.g., provided with a hole(s) through the device, hi some embodiments, one or more cavities 1830 have an erodible and / or biodegradable and / or bioerodible cover.

[0292] In some embodiments, cavity 1830 is located on an outer and / or edge portion of the device, e.g., the portion of the device proximate the outer edge of the device, forming, for example, 5-50% of the device area (e.g., the top view and / or footprint and / or area of ​​one or both of front surface 1818 and back surface 1816).

[0293] In some embodiments, the cavities 1830 are arranged symmetrically on the device 1800, eg, rotationally symmetrically, eg, as shown in Figures 18A and 18B.

[0294] FIG. 19 is a simplified schematic cross-sectional view of an ophthalmic device 1900, according to some embodiments of the present invention.

[0295] In some embodiments, device 1900 includes a body having a posterior surface 1916 and a front surface 1918. In some embodiments, the device includes one or more cavities 1930. In some embodiments, the device includes both cavity(ies) 1930 and protrusion(s) 1934. In some embodiments, device 1900 includes one or more protrusions 1934. In this regard, in some embodiments, protrusion(s) 1934 are located on the posterior surface 1916 of the device, e.g., adjacent to the surface of the eye when the device is placed on the eye.

[0296] In some embodiments, the protrusion(s) 1934 include and / or are formed from a biocompatible material.

[0297] In some embodiments, device 1900 includes between 1 and 50 protrusions, or between 1 and 10 protrusions, or fewer, or more, or an intermediate number of protrusions.

[0298] In some embodiments, one or more of the protrusions are connected and / or linked.

[0299] In some embodiments, one or more of the protrusions are separated, for example, all of the protrusions are separated from one another, as shown in Figures 18A-18B.

[0300] Exemplary protrusion shapes include, for example, balls, domes, cylinders, pyramidal shapes, rectangles, triangles, circles, ellipses, elongated shapes, rounded shapes, rings, partial rings, radial shapes, circumferential shapes, and any other shape.

[0301] In some embodiments, the protrusions have one or more sharp edges and / or acute angles, hi some embodiments, the protrusions have one or more blunt and / or rounded edges and / or corners.

[0302] In some embodiments, the device comprises a plurality of protrusions, wherein one or more of the plurality of protrusions has a different property(ies) than one or more other cavities.

[0303] The protrusions, in some embodiments, are located anywhere on the posterior and / or anterior surfaces. In some embodiments, the protrusion distance 1952 from the surface 1916 of the device to the protrusions 1934 is between about 0.005 mm and about 20 mm. In some embodiments, the size 1950 (e.g., maximum and / or average size) of the protrusions 1934 is between about 0.005 mm and about 20 mm in one or more dimensions perpendicular to the direction of protrusion of the protrusion from the surface 1916 of the device.

[0304] In some embodiments, one or more of the protrusions are erodible.

[0305] In some embodiments, the cavity and / or protrusion is used for insertion and / or removal of the device. For example, in some embodiments, when a finger and / or device is pressed against the cavity or protrusion, suction is released and / or a portion of the device (e.g., an edge) is lifted and / or the device is inverted.

[0306] In some embodiments, the cavities and / or protrusions are used to increase the adhesion of the device, for example, pressure applied to the cavities or protrusions acts to increase the suction force between the device and the surface of the eye.

[0307] In some embodiments, the cavity facilitates inverting the device, eg, from a convex to a concave surface, eg, during insertion.

[0308] In some embodiments, one or more protrusions function as handles, for example, to facilitate application of a pinching force, such as during the removal process, or to facilitate application of pressure and / or stabilization of the device in position, such as when applying it to the sclera.

[0309] 20-28 are simplified schematic bottom views of ophthalmic devices according to some embodiments of the present invention.

[0310] In some embodiments, Figures 20-28 show the rear of the device.

[0311] In some embodiments, the device has a single protrusion and / or a single cavity, such as device 2100 of Figure 21 and / or device 2400 of Figure 24, which in some embodiments include a single cavity 2130, 2430 and in some embodiments include a single protrusion 2130, 2430.

[0312] In some embodiments, the device comprises multiple cavities and / or protrusions, see, for example, Figures 20, 22, 23, 25-28.

[0313] For example, FIG. 20 includes only a plurality of protrusions 2030 in some embodiments, and only a plurality of cavities 2030 in some embodiments.

[0314] In some embodiments, such as in Figures 20, 26, and 28, the cavity(ies) and / or protrusion(s) are arranged radially, eg, radially symmetrically on the device surface.

[0315] In some embodiments, the cavity(ies) and / or protrusion(s) are irregularly distributed on the device surface. In some embodiments, the cavity(ies) and / or protrusion(s) have different sizes and / or shapes, such as in Figures 23, 25, and 27. In some embodiments, the cavities and / or protrusions are disposed in a central region of the surface, such as in cavity and / or protrusion 2734 in Figure 27 and cavity and / or protrusion 2834 in Figure 28.

[0316] In some embodiments, one or more cavities and / or protrusions are elongated, as shown, for example, in Figures 22, 23, and 27.

[0317] 21, in some embodiments, the protrusions and / or cavities 2130 describe a closed shape on the surface of the device, for example, a ring shape 2130.

[0318] In some embodiments, the arrangement of the protrusion(s) and / or cavities is asymmetric and / or irregular, for example as shown in one or more of Figures 24, 25, and 27.

[0319] 26, in some embodiments, the protrusions 2634 and cavities 2630 alternate along the contour of the device. For example, in some embodiments, both the protrusions 2634 and the cavities 2630 are radially disposed, optionally at approximately the same distance from the center and / or edge of the device. In this regard, in some embodiments, the protrusions 2634 and the cavities 2630 alternate along the contour.

[0320] 28, in some embodiments, the cavity(ies) 2834 occupy a central region of the surface of the device, and the protrusions 2030 are positioned at radial distances (e.g., rotationally symmetric) from the central region. In some embodiments, the elements 2834, 2030 are reversed, and the device has protrusion(s) 2834 and cavity(ies) 2030.

[0321] FIG. 29A is a simplified schematic cross-sectional view of a portion of the surface of an eye, according to some embodiments of the present invention.

[0322] FIG. 29B is a simplified schematic cross-sectional view of an ophthalmic device 2900 on the surface of the eye, according to some embodiments of the present invention.

[0323] FIG. 29C is a simplified schematic cross-sectional view of an ophthalmic device 2900 on the surface of the eye, according to some embodiments of the present invention.

[0324] In some embodiments, stroma 2960 is overlain by ocular epithelial layer 2958 , over which resides aqueous tear film layer 2956 , over which resides lipid layer 2954 .

[0325] In some embodiments, FIG. 29A shows a cross section of the anatomy of the eye, for example, before placing the device 2900 on the eye.

[0326] In some embodiments, FIG. 29B shows the device 2900 and the anatomy of the eye immediately and / or shortly after application of the device 2900.

[0327] In some embodiments, FIG. 29C shows the device 2900 and the ocular anatomy after a period of time has passed since the device was worn, which in some embodiments is about 1 minute to 1 hour after wear.

[0328] 29B, in some embodiments, the device body 2900 includes a rear surface 2916 and a front surface 2918. In some embodiments, the body 2900 tapers in thickness towards the edges of the body.

[0329] In some embodiments, device 2900 includes cavities 2930 , 2932 , which in some embodiments are located on posterior surface 2916 .

[0330] In some embodiments, after application of the device, tear fluid fills the cavities 2930, 2932 and the epithelium 2958 remains the same as it was before application of the device. In some embodiments, tear fluid, e.g., aqueous and / or lipid, coats the device (not shown).

[0331] 29C, in some embodiments, after a period of time, the ocular tissue conforms to the shape of device 2900. For example, epithelial tissue 2958 locally protrudes 2960 toward cavities 2930 and 2932, e.g., due to suction at the entrances to the cavities. Potentially, epithelial protrusion(s) 2960 secure device 2900 in place, e.g., reducing the likelihood of device migration and / or expulsion.

[0332] 30A-30C are simplified schematic cross-sectional views of a portion of a device 3000 on the surface of an eye 3058, according to some embodiments of the present invention.

[0333] In some embodiments, FIG. 30A shows the device 3000 and the ocular anatomy 3058 immediately and / or shortly after application of the device 3000.

[0334] In some embodiments, Figure 30B shows the device 3000 and ocular anatomy 3058 after a first period of time has passed since the device was worn, which in some embodiments is between 1 minute and 1 hour.

[0335] In some embodiments, FIG. 30C shows the device 3000 and ocular anatomy 3058 a second time period after the cross-sectional view shown in FIG. 30B, for example, another minute to an hour after the illustration of the device 3000 and ocular anatomy 3058 in FIG. 30B.

[0336] 30A, in some embodiments, the device body 3000 includes a rear surface 3016, which includes a cavity 3030 and a protrusion 3034.

[0337] In some embodiments, after application of the device, tear fluid fills the cavity 3030 and the epithelium 3058 remains the same as it was before application of the device.

[0338] 30B , in some embodiments, after a first period of time, the ocular tissue conforms to the shape of the device 3000. For example, the epithelial tissue 3058 locally protrudes 3060 toward the cavity 3030 and / or indents the pliable epithelial tissue in areas adjacent to the protrusions 3034, forming depressions 3062. At this time, in some embodiments, the indented material potentially anchors the device 3000, thereby potentially reducing the likelihood of device 3000 migration and / or expulsion.

[0339] 30C, in some embodiments, biodegradation and / or bioerosion and / or mechanical erosion of device 3000 occurs. At this time, in some embodiments, protrusions 3034 decrease in size (e.g., in one or more dimensions) and / or the corner(s) of protrusions 3034 become rounded. At this time, in some embodiments, the corners of cavity 3030 become rounded. In some embodiments, the cavity becomes wider in one or more dimensions and / or changes depth, e.g., becomes shallower or deeper (not shown).

[0340] In some embodiments, the proximal surface 3016 in FIG. 30C shows an exemplary proximal surface shape including, for example, protrusion(s) 3034 and / or cavity(ies) 3030.

[0341] FIG. 31A is a simplified schematic cross-sectional view of an ophthalmic device 3100 residing on the surface of an eye 3104, according to some embodiments of the present invention.

[0342] FIG. 31B is a simplified schematic diagram of an ophthalmic device 3100, according to some embodiments of the present invention.

[0343] FIG. 31C is a simplified schematic top view of an ophthalmic device 3100, according to some embodiments of the present invention.

[0344] In some embodiments, the device 3100 includes a rear surface 3116 and a front surface 3118 .

[0345] In some embodiments, the device 3100 includes multiple layers 3110, 3112, where in some embodiments the layers generally conform to the surface of the device.

[0346] In some embodiments, the first layer 3110 is adjacent to and / or in contact with the ocular surface 3104 and / or forms at least a portion of the posterior surface 3116. In some embodiments, the first layer 3110 comprises a mucoadhesive material.

[0347] In some embodiments, the second layer 3112 at least periodically contacts the inner surface of the eyelid and / or forms at least a portion of the anterior surface 3114. In some embodiments, the second layer has a smooth outer surface and / or comprises a lubricating material. In some embodiments, one or both of the first layer 3110 and the second layer 3112 comprise and / or elute a therapeutic substance(s).

[0348] 31B illustrates, in some embodiments, determining the size of the device 3100, where the size is one or more dimensions and / or the average of two or more dimensions of the smallest rectangular shaped bounding box 3164 into which the device 3100 can fit.

[0349] In some embodiments, device 3100 includes one or more additional layers (eg, as described elsewhere herein).

[0350] In some embodiments, the thickness 3128 of the ophthalmic device (e.g., maximum thickness in the central 50% of the device and / or average thickness) is less than 100 microns. In some embodiments, the thickness of the ophthalmic device is from about 1 to about 200 microns. In some embodiments, the device has a thickness of about 1 micron, or about 2 microns, or about 3 microns, or about 4 microns, or about 5 microns, or about 6 microns, or about 7 microns, or about 8 microns, or about 9 microns, or about 10 microns, or about 15 microns, or about 20 microns, or about 25 microns, or about 30 microns, or about 35 microns, or about 40 microns, or about 45 microns, or about 50 microns, or about 55 microns, or about 60 microns, or about 70 microns, or about 80 microns, or about 90 microns, or about 100 microns, or about 110 microns, or about 120 microns, or about 130 microns, or about 140 microns, or about 150 microns, or about 160 microns, or about 170 microns, or about 180 microns, or about 190 microns, or about 200 microns. In some embodiments, the device has a thickness of about 10 to about 100 microns.

[0351] In some embodiments, the first layer (e.g., mucoadhesive layer) 3166, and / or the second layer (e.g., lubricious layer) 3164, and / or any additional intermediate layer(s) (e.g., as described elsewhere herein) have a thickness (e.g., maximum thickness and / or average thickness in the central 50% of the device) of less than 100 microns. In further embodiments, the thickness of one or more layers is from about 1 to about 200 microns. In some embodiments, the lubricating layer and / or mucoadhesive layer and / or intermediate layer have a thickness of about 1 micron, 2 microns, 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, 15 microns, 20 microns, 25 microns, 30 microns, 35 microns, 40 microns, 45 microns, 50 microns, 55 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns, 150 microns, 160 microns, 170 microns, 180 microns, 190 microns, or 200 microns. In some embodiments, the thickness of one or more layers is from about 1 to about 10 microns.

[0352] In some embodiments, one or more layers have approximately the same thickness as one or more other layers. In some embodiments, one or more layers have a different thickness than one or more other layers. In some embodiments, one or more layers have a non-uniform thickness, e.g., thinning outward from the central region of the device toward the edge region(s) of the device. For example, a layer has cavities and / or holes and / or protrusion(s).

[0353] 32-37 are simplified schematic cross-sectional views of portions of ophthalmic devices according to some embodiments of the present invention.

[0354] In some embodiments, the shaded areas in Figures 32-37 indicate the presence of the therapeutic component(s).

[0355] 32 and 35, in some embodiments, the second layer 3212, 3512 (e.g., including one or more features described with respect to the second layer 3112 of FIGS. 31A-31C ) includes a therapeutic component(s). For example, the therapeutic component(s) are dispersed within the second layer 3112 and / or disposed within one or more regions 3514 of the second layer 3512.

[0356] 33 and 36, in some embodiments, the first layer 3310, 3610 (e.g., including one or more features described with respect to the first layer 3110 of FIGS. 31A-31C ) includes a therapeutic component(s). For example, the therapeutic component(s) are dispersed within the first layer 3110 and / or disposed within one or more regions 3614 of the first layer 3610.

[0357] 34 and 37, in some embodiments, both the first layer 3410, 3710 (e.g., including one or more features described with respect to the first layer 3110 of FIGS. 31A-31C ) and the second layer 3412, 3712 (e.g., including one or more features described with respect to the second layer 3112 of FIGS. 31A-31C ) include a therapeutic component(s). For example, the therapeutic component(s) are dispersed within the first layer 3410 and / or the second layer 3412 and / or disposed within one or more regions 3714 of the second layer 3712 and / or the first layer 3710. Alternatively, in some embodiments, one of the layers has a portion with a therapeutic substance, while the other layer has the therapeutic substance dispersed therein (not shown). In some embodiments, the distinct region(s) containing the therapeutic substance include a different therapeutic substance than the layer in which the therapeutic substance is dispersed. In some embodiments, the distinct region(s) are encapsulated with other materials, for example, in some embodiments, after the material erodes, the therapeutic substance begins to elute into the eye.

[0358] 38-44 are simplified schematic cross-sectional views of devices 3800, 3900, 4000, 4100, 4200, 4300, 4400 according to some embodiments of the present invention.

[0359] In some embodiments, the device has a flat or high radius of curvature posterior surface, such as posterior surface 3816 of device 3800 in Figure 38, such as posterior surface 3916 of device 3900 in Figure 39, such as posterior surface 4016 of device 4000 in Figure 40, or posterior surface 4116 of device 4100 in Figure 41. Here, in some embodiments, the high radius of curvature is greater than 5 mm, or greater than 10 mm, or greater than 9.6 mm, or between 8 and 12 mm, or between 9 and 11 mm, or smaller, or larger, or intermediate radii or ranges.

[0360] In some embodiments, a device has a concave rear surface, such as rear surface 4216 of device 4200, such as rear surface 4316 of device 4300, or such as rear surface 4416 of device 4400. Here, in some embodiments, concave rear surface 4216, 4316, 4416 includes one or more features shown and / or described with respect to concave and / or curved rear surface(s) elsewhere herein.

[0361] In some embodiments, the device and / or cross-section of the device comprises a single cavity, for example, in some embodiments, elements 3830, 3930, 4030 of Figures 38-40 are each cavities, and in some embodiments, cavities 3830, 3930, 4030 are located on rear surfaces 3816, 3916, 4016 of the device.

[0362] In some embodiments, the device and / or cross-section of the device may comprise a single portion having a different material, e.g., a mucoadhesive material, e.g., in some embodiments, elements 3830, 3930, 4030 of Figures 38-40 are each mucoadhesive portions, such that in some embodiments, mucoadhesive portions 3830, 3930, 4030 are located on the rear surface 3816, 3916, 4016 of the device, respectively.

[0363] 41 and 42. In some embodiments, the device and / or cross-section of the device includes a single portion 4130, 4230 having a different material, for example a mucoadhesive material, and includes a single cavity 4132, 4232. In some embodiments, the cavity 4130, 4230 and the different material portion 4132, 4232 are disposed on the rear surface 4116, 4216 of the device 4100, 4200, respectively.

[0364] In some embodiments, the device and / or a cross section of the device has two portions of different material(s), with portions 4130, 4132 of device 4100 and / or portions 4230, 4232 of device 4200 having the same material or different materials.

[0365] In some embodiments, the device 4100, 4200 and / or a cross section of the device has two cavities 4130, 4132 and two cavities 4230, 4232, respectively.

[0366] 43 and 44, in some embodiments, a device 4300, 4400 has both a plurality of concave surfaces 4330, 4430 and a plurality of distinct material portions 4332, 4432, all of which in some embodiments are located on the rear surface 4316, 4416, respectively, of the device 4300, 4400. In some embodiments, one or more of the cavities and / or one or more of the distinct material portions are located within the body of the device and / or on a distinct device surface, for example, on the front surface 4318, 4418 of the device.

[0367] Referring now to FIG. 43, in some embodiments, the cavity(ies) 4330 are positioned more centrally with respect to the surface 4316 and / or device body 4300 on the rear surface 4316 compared to the different material portion (e.g., adhesive portion)(ies) 4332.

[0368] Referring now to FIG. 44, in some embodiments, the different material portion (e.g., adhesive portion)(s) 4432 are positioned more centrally with respect to the surface 4416 and / or device body 4400 on the rear surface 4416 compared to the cavity(ies) 4430.

[0369] 45-50 are simplified schematic cross-sectional views of dual layer devices 4500, 4600, 4700, 4800, 4900, 5000, according to some embodiments of the present invention.

[0370] In some embodiments, devices 4500, 4600, 4700, 4800, 4900, 5000 have rear surfaces 4516, 4616, 4716, 4816, 4916, 5016, respectively, and front surfaces 4518, 4618, 4718, 4818, 4918, 5018, respectively.

[0371] In some embodiments, devices 4500, 4600, 4700, 4800, 4900, 5000 include a first layer 4510, 4610, 4710, 4810, 4910, 5010 and a second layer 4512, 4612, 4712, 4812, 4912, 5012, where in some embodiments the first layer has one or more features described and / or illustrated with respect to first layer 3110 of Figures 31A-31C and / or one or more of first layers 3210, 3310, 3410, 3510, 3610, 3710 of Figures 32-37, respectively. In this regard, in some embodiments, the second layer has one or more features described and / or illustrated with respect to second layer 3112 of Figures 31A-31C and / or one or more of second layers 3212, 3312, 3412, 3512, 3612, 3712 of Figures 32-37, respectively.

[0372] In some embodiments, the device has a flat posterior surface or a posterior surface of low curvature (e.g., as defined elsewhere herein) in a dry and / or hydrated state, such as posterior surface 4516 in Figure 45, posterior surface 4616 in Figure 46, posterior surface 4716 in Figure 47, or posterior surface 4916 in Figure 49.

[0373] 45 and 47, in some embodiments, the second layer 4512, 4712 (e.g., comprising a lubricating material) extends around the body of the device, for example, covering the edge(s) 4568 and / or forming portion(s) of the proximal surface 4516, 4716 of the device (e.g., portion(s) at the edge(s)).

[0374] 45-47, in some embodiments, the first layer and / or the second layer have a substantially uniform thickness across the area of ​​the device and / or along one or more cross sections of the device, such as layers 4510, 4512 in FIG. 45, layers 4610, 4612 in FIG. 46, and 4710, 4712 in FIG. 47.

[0375] 47-50. In some embodiments, one or more layers have one or more maximum thicknesses in the center and / or central region of the device and decrease in thickness moving from the central region toward the edge(s) of the device, such as layer 4710 in FIG. 47, layers 4810, 4812 in FIG. 48, layers 4910, 4912 in FIG. 49, and layer 5012 in FIG. 50.

[0376] 45 shows a device 4500 having a flat and / or low curvature posterior surface 4516 and an anterior surface 4518, in some embodiments, where the second layer 4512 extends around the edges of the device 4500 and forms part of the anterior surface 4518, where the layers individually have a substantially uniform thickness.

[0377] FIG. 46 shows a device having a posterior surface 4616 and an anterior surface 4618 that are flat and / or have low curvature, with the layers individually having approximately uniform thickness, in some embodiments.

[0378] 47 shows a device 4700 having a flat and / or low curvature posterior surface 4716 and a convex anterior surface 4718 in some embodiments, where the second layer 4712 extends around the edges of the device 4700 and forms part of the anterior surface 4718. In some embodiments, the second layer 4712 has a substantially uniform thickness. In some embodiments, the first layer 4710 has a maximum thickness in the center and / or central region of the device and decreases in thickness moving from the central region toward the edge(s) of the device 4700.

[0379] 48 shows a device 4800 having, in some embodiments, both a concave posterior surface 4816 and a convex anterior surface 4818. Here, in some embodiments, both the first layer 4810 and the second layer 4812 have one or more maximum thicknesses in the center and / or central region of the device, decreasing in thickness as one moves from the central region toward the edge(s) of the device 4800.

[0380] 49 shows a device 4900 in some embodiments where the posterior surface 4916 is flat or has a low curvature and the anterior surface 4918 is convex, such that in some embodiments, both the first layer 4910 and the second layer 4912 have one or more maximum thicknesses in the center and / or central region of the device, decreasing in thickness as you move from the central region toward the edge(s) of the device 4900.

[0381] 50 illustrates a device 5000 in some embodiments, where the rear surface has a convex boundary plane. In some embodiments, the rear surface has one or more protrusions 5034 and / or one or more cavities 5030. For example, a cross section may have two protrusions 5034 defining a cavity 5030 therebetween. In some embodiments, the thickness of one or both layers is irregular. In some embodiments, the rear surface 5016 has an irregular shape.

[0382] 51-58 are simplified schematic cross-sectional views of multi-layer devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, according to some embodiments of the present invention.

[0383] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 have rear surfaces 5116, 5216, 5316, 5416, 5516, 5616, 5716, 5816, respectively, and front surfaces 5118, 5218, 5318, 5418, 5518, 5618, 5718, 5818, respectively.

[0384] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 include a first layer (e.g., mucoadhesive layer) 5110, 5210, 5310, 5410, 5510, 5610, 5710, 5810 and a second layer (e.g., lubricious layer) 5112, 5212, 5312, 5412, 5512, 5612, 5712, 5812, where in some embodiments, the first layer has one or more features described and / or illustrated with respect to first layer 3110 of Figures 31A-31C and / or one or more of first layers 3210, 3310, 3410, 3510, 3610, 3710 of Figures 32-37, respectively. In this regard, in some embodiments, the second layer has one or more features described and / or illustrated with respect to second layer 3112 of Figures 31A-31C and / or one or more of second layers 3212, 3312, 3412, 3512, 3612, 3712 of Figures 32-37, respectively.

[0385] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 include intermediate layers 5136, 5236, 5336, 5436, 5536, 5636, 5736, 5836, respectively. In some embodiments, the intermediate layer is disposed between the first layer and the second layer. In this regard, in some embodiments, the intermediate layer is covered by another layer, as shown, for example, in Figures 51-55 and 57-58. In some embodiments, the intermediate layer includes a therapeutic substance (e.g., dispersed within and / or in portion(s) of the layer).

[0386] FIG. 51 illustrates a device 5100 having a posterior surface 5116 and an anterior surface 5118 that are flat and / or have low curvature, in some embodiments. Here, in some embodiments, the second surface extends to cover the edges of the device 5100, for example, to wrap around the sides of the intermediate surface 5136. In some embodiments, one or more (e.g., all) of the first layer 5110, second layer 5112, and third layer 5136 have a substantially uniform thickness. In some embodiments, the thickness of the intermediate layer 5136 is thicker than one or more of the other layers, for example, by 1.5 to 10 times, or by a smaller, larger, or intermediate multiple or range of thickness.

[0387] 52 shows some embodiments of device 5200, where posterior surface 5216 is convex. In some embodiments, first layer 5210 and second layer 5212 have approximately the same thickness, and in some embodiments, approximately uniform thickness. In some embodiments, middle layer 5236 is thicker in a central region and decreases in thickness toward the edges of device 5200. In some embodiments, the average and / or maximum thickness of middle layer 5236 is 1.5 to 10 times the thickness of one or both of first layer 5210 and second layer 5212.

[0388] 53 shows a device 5300 in some embodiments, where each of the first layer 5310, middle layer 5336, and second layer 5312 is thicker in a central region and decreases in thickness toward the edges of the device 5300. In some embodiments, the second layer 5312 is disposed around the periphery of the device 5300 and forms part of the posterior surface 5316. In some embodiments, the posterior surface 5316 has a larger radius of curvature than the anterior surface 5318 (e.g., has a radius of curvature that includes one or more features described elsewhere herein, for example, in the Overview section).

[0389] 54 shows a device 5400 in some embodiments in which the first layer 5410, the middle layer 5436, and the second layer 5412 are each thicker in a central region and decrease in thickness toward the edges of the device 5400. In some embodiments, the thicknesses of the layers are approximately the same in the central region of the device and / or across one or more cross sections of the device.

[0390] In some embodiments, the device 5500 of FIG. 55 has the same features as the device 5100 of FIG. 51, except that the intermediate layer 5536, in some embodiments, is approximately the same thickness as one or both of the first layer 5510 and the second layer 5512.

[0391] 56 illustrates a device 5600 in some embodiments, where each layer 5610, 5612, 5636 has a constant thickness along the cross section shown. In some embodiments, the intermediate layer 5636 includes a therapeutic substance. In some embodiments, the intermediate layer 5636 is thicker than one or both of the other layers 5612, 5610. For example, the intermediate layer 5636 may be 1.5 to 10 times thicker than the mucoadhesive layer 5610 and / or the lubricious layer 5612. In some embodiments, the intermediate layer 5636 includes multiple layers.

[0392] 57 shows a device 5700 having a convex anterior surface 5718 and a flat or low-curvature posterior surface 5716 in some embodiments. In some embodiments, the mucoadhesive layer 5716 has a uniform thickness across one or more cross sections of the device. In some embodiments, the lubricious layer 5712 has a uniform thickness in a path surrounding the periphery of the intermediate layer 5736. In some embodiments, the intermediate layer 5736 is thicker in a central region of one or more cross sections of the device 5700 and, in some embodiments, decreases in thickness toward the edge(s) of the device. In some embodiments, the lubricious layer 5712 does not form part of the posterior surface 5716.

[0393] 58 shows a device 5800 having a convex anterior surface 5818 and a concave posterior surface 5816 in some embodiments. In some embodiments, the mucoadhesive layer 5816 has a uniform thickness across one or more cross sections of the device. In some embodiments, the lubricious layer 5812 has a uniform thickness along a path around the periphery of the intermediate layer 5836. In some embodiments, the intermediate layer 5836 is thicker in a central region of one or more cross sections of the device 5800 and, in some embodiments, decreases in thickness toward the edge(s) of the device. In some embodiments, the lubricious layer 5812 does not form part of the posterior surface 5816.

[0394] 59-61 are simplified schematic cross-sectional views of multi-layer devices 5900, 6000, 6100, according to some embodiments of the present invention.

[0395] Figures 59-61 show the elution of therapeutic components in some embodiments, indicated by arrows in the figures.

[0396] 59, in some embodiments, the middle layer 5936 includes a therapeutic substance and is not covered by other layer(s) at the edges of the device 5900. This layer, in some embodiments, elutes the therapeutic component(s) through the edges, for example, as indicated by the arrows.

[0397] 60, in some embodiments (e.g., instead of or in addition to eluting through the edge of the device), the middle layer 6036 includes a therapeutic substance and is not completely covered by the second lubricious layer 6012, with the therapeutic component(s) eluting through the second layer, for example, through the channel(s) and / or holes 6030 in layer 6012, as indicated by the arrows in FIG. 60. In some embodiments, instead of or in addition to having channel(s) and / or holes, the second layer 6012 includes a material that allows the therapeutic component(s) to diffuse through the material.

[0398] 61 , in some embodiments (e.g., instead of or in addition to eluting through the edge of the device and / or through the second lubricious surface 6112), the intermediate layer 6136 comprises a therapeutic substance and is not completely covered by the first mucoadhesive layer 6110, with the therapeutic component(s) eluting through the first layer, for example, through the channel(s) and / or holes 6130 in the layer 6110, as indicated by the arrows in FIG. 61 . In some embodiments, instead of or in addition to having channel(s) and / or holes, the first layer 6110 comprises a material that allows the therapeutic component(s) to diffuse through the material.

[0399] Exemplary Collapse of Exemplary Ophthalmic Devices 62A-62F are simplified schematic cross-sectional views of a portion of a device over the course of the device's dwell time, according to some embodiments of the present invention.

[0400] FIG. 63 is a flowchart of the device's decay progression, according to some embodiments of the present invention.

[0401] FIG. 62A shows the device layer structure before the device is placed on the surface of the eye in some embodiments. The device comprises a first mucoadhesive layer 6210 , an intermediate layer 6236 , and a second lubricious layer 6212 .

[0402] At 6300, in some embodiments, the device 6200 is placed on the surface 6258 of the eye.

[0403] At 6302, in some embodiments, the mucoadhesive layer 6210 degrades and / or dissolves and / or erodes, for example, causing the device 6200 to transition from the configuration shown in FIG. 62B to the configuration shown in FIG. 62C.

[0404] At 6304, in some embodiments, the intermediate layer 6236 partially decomposes and / or dissolves and / or erodes, for example, causing the device 6200 to transition from the configuration shown in FIG. 62C to the configuration shown in FIG. 62D and then to the configuration shown in FIG. 62E.

[0405] At 6306, in some embodiments, the lubricious layer 6212 dissolves and / or decomposes and / or erodes, for example, causing the device 6200 to transition from the structure shown in FIG. 62E to the structure shown in FIG. 62F.

[0406] 64A-64C are simplified cross-sectional schematic illustrations of a device 6400 over the course of the device's residence time, according to some embodiments of the present invention.

[0407] In some embodiments, Figures 64A-64C show only a portion of the device (eg, the center portion is shown, the edges are not shown).

[0408] In Figures 64A-64C, in some embodiments, like shading indicates portions having the same material properties (eg, lubricious, mucoadhesive, containing a therapeutic substance, etc.).

[0409] In some embodiments, device 6400 includes a rear surface 6416 and a front surface 6418, one or both of surfaces 6416, 6418 having one or more characteristics (e.g., curvature, thickness) shown and / or described elsewhere herein.

[0410] In some embodiments, the device 6400 comprises a first mucoadhesive layer 6410 and a second lubricious layer 6412 .

[0411] In some embodiments, the mucoadhesive layer 6410 then covers most (e.g., 55-99%, or 60-90%, or lower, higher, or intermediate ranges or percentages) or all of the posterior surface 6416. A potential advantage of a mucoadhesive layer over a larger surface is increased stability, for example, with improved adhesion to the ocular surface.

[0412] At this time, in some embodiments, the lubricating layer 6412 covers a portion of the front surface 6418, for example, the edge region(s).

[0413] In some embodiments, device 6400 includes a third layer 6470, where in some embodiments, third layer 6470 includes a material that dissolves and / or decomposes and / or wears away rapidly, where in some embodiments, the third layer disintegrates more rapidly than the other layer(s) of device 6400. For example, as shown in the transitions of FIGS. 64A-64B, the thickness of third layer 6470 decreases.

[0414] In some embodiments, the mucoadhesive layer 6410 also erodes (e.g., with proximity to the ocular surface, not shown, and / or with the material properties of the layer) and / or dissolves and / or degrades (e.g., with the material properties) more readily than one or more other layers of the device. For example, as shown in the transitions of Figures 64A-64B, the thickness of the mucoadhesive layer 6410 decreases.

[0415] In some embodiments, the intermediate layer 6436 includes a therapeutic substance and, upon exposure due to the disappearance of the third layer 6470, the intermediate layer 6436 begins to dissolve and / or degrade and / or erode, e.g., eluting the drug. In some embodiments, the intermediate layer dissolves and / or degrades and / or erodes more readily than other layers, e.g., the lubricious layer 6412 and / or the mucoadhesive layer 6416, as indicated, e.g., by the cavities 6430 formed in the intermediate layer 6436.

[0416] 65A-65D are simplified cross-sectional schematic illustrations of a device over time as the device dwells, according to some embodiments of the present invention.

[0417] In some embodiments, Figures 65A-65D show only a portion of the device (eg, the center portion is shown, the edges are not shown).

[0418] In Figures 65A-65D, in some embodiments, like shading indicates portions having the same material properties (eg, lubricious, mucoadhesive, containing a therapeutic substance, etc.).

[0419] In some embodiments, the device 6500 has a rear surface 6516 and a front surface 6518, one or both of the surfaces 6516, 6518 having one or more characteristics (e.g., curvature, thickness) shown and / or described elsewhere herein.

[0420] In some embodiments, the device 6500 comprises a first mucoadhesive layer 6510 and a second lubricious layer 6512. In some embodiments, the device 6500 comprises an intermediate therapeutic substance layer 6536.

[0421] In this regard, in some embodiments, one or more (e.g., all) of the lubricating layer 6512 and the mucoadhesive layer 6510 are disposed in an edge region(s) of the device 6500, and are not present, for example, in the central region of the device 6500.

[0422] In some embodiments, the device 6500 includes a third layer 6570. Here, in some embodiments, the third layer 6570 comprises a material that dissolves and / or decomposes and / or wears away rapidly. Here, in some embodiments, the third layer disintegrates more rapidly than the other layer(s) of the device 6500. For example, as shown in the progression of FIGS. 65A-65B-65C, the third layer 6570 decreases in thickness, and then, in the transition of FIGS. 65C-65D, the third layer 6570 disappears. In some embodiments, for example, as shown in the transition of FIGS. 65A-65B, the mucoadhesive layer 6510 disappears first, exposing, for example, the intermediate therapeutic substance layer 6536. In some embodiments, for example, as shown in FIG. 65D, the third layer 6570 disappears, leaving one or more remaining layer(s) at the edge of the device. In some embodiments, the device 6500 is placed over an area of ​​the eye, for example over the cornea, and the disappearance of the third layer 6570 creates a hole in the device, and the device 6500 is placed over, for example, the sclera surrounding the cornea.

[0423] FIG. 66 is a simplified schematic cross-sectional view of a device 6600, according to some embodiments of the present invention.

[0424] In some embodiments, FIG. 66 shows only a portion of the device (eg, the center portion is shown, the edges are not shown).

[0425] In Figure 66, in some embodiments, like shading indicates portions having the same material properties (eg, lubricious, mucoadhesive, containing a therapeutic substance, etc.).

[0426] In some embodiments, the device 6600 has a rear surface 6616 and a front surface 6618, one or both of the surfaces 6616, 6618 having one or more characteristics (e.g., curvature, thickness) shown and / or described elsewhere herein.

[0427] In some embodiments, the device 6600 comprises a first mucoadhesive layer 6610 and a second lubricious layer 6612 . In some embodiments, the device 6600 includes an intermediate therapeutic substance layer 6636. In some embodiments, the mucoadhesive layer 6610 covers most or all of the posterior surface 6616 of the device.

[0428] At this time, in some embodiments, one or more of the lubricating layer 6612 and the intermediate therapeutic substance layer 6636 are disposed in an edge region(s) of the device 6600 and are not present in the central region of the device 6600, for example.

[0429] In some embodiments, device 6600 includes a third layer 6670, wherein in some embodiments, third layer 6670 includes a material that dissolves and / or decomposes and / or wears away rapidly, wherein in some embodiments, the third layer disintegrates more rapidly than the other layer(s) of device 6600.

[0430] In some embodiments, the device 6600 includes a degrading layer 6672, which in some embodiments degrades more rapidly than one or more of the mucoadhesive layer 6610, the lubricious layer 6612, and the therapeutic layer 6636. At this time, in some embodiments, the degrading layer 6672 degrades and / or dissolves and / or erodes more slowly than the third layer 6670.

[0431] At this time, in some embodiments, the third layer 6670 disappears first, e.g., exposing a portion(s) of the therapeutic layer 6636, and elution of the therapeutic substance begins and / or increases. At this time, in some embodiments, the degradation layer 6672 erodes next, e.g., exposing more of the therapeutic substance layer and / or causing the device to degrade.

[0432] FIG. 67 is a simplified schematic cross-sectional view of a device 6700, according to some embodiments of the present invention.

[0433] In some embodiments, the device 6700 has a rear surface 6716 and a front surface 6718, one or both of the surfaces 6716, 6718 having one or more characteristics (e.g., curvature, thickness) shown and / or described elsewhere herein.

[0434] In some embodiments, the anterior surface 6718 includes a region of low curvature (or flat region) located in a central region of the device 6700. In some embodiments, the anterior surface 6718 curves toward the posterior surface 6716.

[0435] In some embodiments, the device 6700 includes a first mucoadhesive layer 6710 and a second lubricious layer 6712. In some embodiments, the device 6700 includes an intermediate therapeutic substance layer 6736. In some embodiments, the second surface 6712 curves around an edge(s) of the device 6700, for example, in some embodiments, forming an edge portion of the rear surface 6716.

[0436] In some embodiments, the mucoadhesive layer 6710 occupies a marginal region of the device 6700 and / or the rear surface 6716 .

[0437] A potential advantage of placing the mucoadhesive locally at the edges of the device 6700, for example as recesses in the intermediate therapeutic substance layer 6736, is that it provides the adhesive benefits of a mucoadhesive material while preserving more device volume for the therapeutic substance. In some embodiments, the intermediate therapeutic substance layer 6736 forms at least a portion of the posterior surface 6716. A potential advantage is that the components elute rapidly after the device 6700 is attached to the surface of the eye.

[0438] Exemplary Materials In some embodiments, one or more portions of the ophthalmic device include one or more of a film former(s), a plasticizer(s), a binder(s), and an excipient(s).

[0439] In some embodiments, the device comprises one or more of anti-infective and anti-inflammatory medications (including glucocorticoids, NTHE, and biologics, or combinations thereof), as well as other technologies and procedures such as silver, gold, zinc oxide, titanium oxide, selenium, copper, polyammonium salts, signal transduction inhibitory and antimicrobial peptides, cytokines, enzymes, and the like.

[0440] In some embodiments, the device comprises a heat sensitive compound and / or a pH sensitive compound and / or an ion sensitive compound.

[0441] Without being bound by theory, the molecular weight and / or degree of crosslinking of compounds within the material of the device contribute to the consistency (e.g., hardness and / or rigidity) of the device and / or contribute to the rheological properties (e.g., viscosity) of the device, where in some embodiments, the molecular weight and / or crosslinking and / or consistency and / or rheological properties define the residence time of the device and / or release rate of the therapeutic agent.

[0442] In some embodiments, the device composition includes at least one charged compound, hi some embodiments, the device composition includes at least one charged compound and at least one compound with an opposite charge, which assembles into a PEC (polyelectrolyte complex) structure upon liquid adsorption.

[0443] The lubricious portion (e.g., lubricious layer and / or lubricious film), and / or the mucoadhesive portion (e.g., mucoadhesive layer and / or mucoadhesive film), and / or other portion(s) of the ophthalmic device may comprise one or more of those (and / or similar compound(s) and / or material(s) and / or polymer(s) and / or combinations thereof) listed herein as non-limiting exemplary material(s). Polyethylene phthalate polymer film; for example, purchased in film form (MYLAR-A®; DuPont, USA). Polyvinyl alcohol 4-88; purchased e.g. as powder (Merck, Germany). Methocel LV-50; purchased as a powder (DOW, USA). Polyvinyl alcohol; purchased e.g. as a powder (Merck, Germany). Polyvinyl alcohol [PVA]: polyethylene glycol [PEG] graft copolymer; purchased, for example, as a powder (Kollicoat-IR®; BASF, Germany). Hydroxypropyl cellulose polymers; purchased as powders, for example (Klucel-LF®; Ashland, USA) povidone (Kollidone 25; BASF, Germany). Carbomer, Carbopol, Carbopol 971, Carbopol 974, Carbopol 934, Carbopol 2020. Cross-linked polyacrylic acid; purchased, for example, as a powder (Carbopol 974; Lubrizol, USA). Cross-linked sodium polyacrylate; purchased e.g. as a powder (FavorPac®; Evonik, Germany). Cross-linked sodium polyacrylate; purchased, for example, as a powder (Luquasorb®; BASF, USA). Sodium CMC, polycarbophil, tragacanth, polyacrylic acid polymer, sodium alginate, (poly)hydroxyethylcellulose, HPMC, karaya gum, gelatin, guar gum, starch, modified starch, pectin, psyllium, amberlite resin, hydroxypropyl cellulose. Chitosan; purchased e.g. as a powder (KiOnutrime-CsG; Kitozyme, Belgium). Chitosan; purchased, for example, as a powder (Chitoclear, Premix, Iceland, or 90 / 200 / A1; Kraeber, Germany, or Protasan UP CL 114, 113, 213, 214; Novamatrix, Norway). Alginate, gellan gum, Eudragit. Polyethylene oxide, carboxymethyl cellulose (CMC), poly(methyl vinyl ether), poly(methyl vinyl ether)-co-maleic anhydride, hydroxypropyl methylcellulose, methyl ethyl cellulose, polyhydroxyethyl methacrylate. methylcellulose or hypromellose or povidone (Kollidone 25; BASF, Germany), or polyvinylpyrrolidone (PVP). Cross-linked polyglutamic acid; purchased as a powder, e.g., (PGA; Hayashibara, Japan). Cross-linked dextran gel; e.g., purchased as a powder (Sephadex G-100; GE Medical). Lactose monohydrate; purchased e.g. as a powder (Pharmatose 200, Fonterra, New Zealand). Cellulose acetate, ethyl cellulose, methyl cellulose, modified cellulose. Silicones, acrylates, polyethylene (including ultra-high molecular weight polyethylene terephthalate), polyesters. Polypropylene, polytetrafluoroethylene (PTFE, ePTFE), polyetheretherketone (PEEK), nylon. Biocompatible metal alloy. Polymer foam. Polymethyl methacrylate (PMMA), polyhydroxyethyl methacrylate (pHEMA). Cellulose acetate butyrate, siloxane acrylate, t-butylstyrene, fluorosiloxane acrylate, perfluoroether. Silicone Hydrogel, Lotrafilcon A, Lotrafilcon B, Galifilcon A, Senofilcon A, Senofilcon C, Sifilcon A, Confilcon A, Enfilcon A, Balafilcon A, Derefilcon A, Narafilcon B, Narafilcon A, Stenfilcon A, Somofilcon A, Famfilcon A, Samfilcon A, Elastofilcon. Tefilcon, Tetrafilcon A, Clofilcon, Herfilcon A / B, Mafilcon, Polymacon, Hyoxifilcon B. Sarfilcon A, Lidofilcon A, Lidofilcon B, Netrafilcon A, Hefilcon B, Alfafilcon A, Mafilcon A, Omafilcon B, Basulfilcon A, Hyoxifilcon A, Hyoxifilcon D, Nelfilcon A, Hilafilcon A, Hilafilcon B, Acofilcon A, Nesofilcon A. Bufilcon A, Deltafilcon A, Femfilcon. Bufilcon A, Perfilcon A, Etafilcon A, Focofilcon A, Ocfilcon B, Ocfilcon C, Ocfilcon D, Ocfilcon E, Ocfilcon F, Femfilcon A, Metafilcon A, Metafilcon B, Bilfilcon A. Lotrafilcon A, balafilcon A, senofilcon A, galyfilcon A, samfilcon A, comfilcon A, enfilcon A, etc. PHEMA (Polyhydroxyethyl methacrylate), MA (Methacrylic acid), MMA (Methyl methacrylate), GMA (Glyceryl methacrylate), DAA (Diacetone acrylamide), PVOH (Polyvinyl alcohol), PVA (Polyvinyl acetate). Silicone rubber, acrylic resin, polyurethane, polypropylene, and polymethyl methacrylate, polycarbonate urethane, polyimide. Polyglycolide, polylactide, polyhydroxobutyrate, hyaluronic acid, and the hydrogel, poly(2-hydroxyethyl methacrylate). Polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid (PLGA), and poly(caprolactone). Polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymer, polyorthoesters, polyhydroxybutyrate, polyanhydrides, polyphosphate esters, poly(alpha hydroxy acids). Polycaprolactone (PCL), polyesteramide (PEA). Proteins, fatty acids, amino acids, carbohydrates, collagen. Poloxamer, Synperonic, Pluronic®, Corifol, Pluronic® F127 (BASF), Synperonic PE / F127 (Croda), Poloxamer 188 (Pluronic® F-68), Poloxamer 407 (Pluronic® F-127), Polypropylene Glycol, Polyoxyethylene, Poly(propylene oxide), Carboxylated Polystyrene, PEGylated Polystyrene, Dendrimer, Poly(amidoamine) (PAMAM). Polyethylene glycol (Sigma, USA). Triethyl citrate [TEC] and acetyl tributyl citrate [ATBC]; purchased, for example, as liquids (Merck, Germany). Tris(hydroxymethyl)aminomethane. DEP [diethyl phthalate]; purchased e.g. as a liquid (Spectrum, USA). Glycerol monostearate [GMS]; purchased e.g., in liquid form (Cognis, Germany). Ethanol, methanol, isopropyl alcohol [IPA], ethyl acetate, acetic acid, and acetone (BioLab, Israel); organic solvents used to dissolve the polymer. Hypromellose phthalate [HP-55] and hypromellose acetate succinate [AQOAT AS-LF]; for example, purchased as a powder (Shin-Etsu, Korea), CAP [cellulose acetate phthalate] and CA [cellulose acetate]; for example, purchased as a powder (Eastman, USA). Polysaccharides (beta-cyclodextrin, dextran, inulin, etc.), sugars (glucose, lactose, leucrose, maltose, raffinose, sucrose, trehalose, etc.), polyols (maltitol, mannitol, sorbitol, xylitol, etc.), oligosaccharides, carbohydrates. Heat sensitive compounds, or pH sensitive compounds, or ion sensitive compounds, or pressure sensitive compounds, or polarization sensitive compounds. Excipients, including: anti-adherents, binders and adhesives (including mucoadhesives), coating agents, colorants, disintegrants, flavors, glidants, lubricants, preservatives, adsorbents, sweeteners, vehicle. One or more solvents, such as one or more of ethanol, methanol, isopropanol, methylene chloride, ethyl acetate, acetone, water, ethanol, polyols (glycerol, propylene glycol, polyethylene glycol, etc.).

[0444] Exemplary Lubrication Layers In some embodiments, the lubricating portion (e.g., lubricating layer) comprises one or more of cellulose acetate, ethyl cellulose, PVA (polyvinyl alcohol), polyvinyl alcohol [PVA]:polyethylene glycol [PEG] graft copolymer, or PVA (polyvinyl acetate), or PVA (polyvinyl acetate) or methyl cellulose.

[0445] Exemplary Mucoadhesive Layers In some embodiments, the term "mucoadhesive" encompasses any compound capable of adhering to biological tissue. In some embodiments, the mucoadhesive is a polymer. In some embodiments, the mucoadhesive is charged or neutral.

[0446] In some embodiments, the mucoadhesive portion (eg, mucoadhesive layer) comprises one or more components configured to provide mucoadhesive properties.

[0447] In some embodiments, the mucoadhesive portion (e.g., mucoadhesive layer) comprises one or more of polyvinyl alcohol (also referred to as PVA or PVOH), hydroxypropyl cellulose (Klucel), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat-IR), methylcellulose, hypromellose methylcellulose, hydroxypropyl methylcellulose (Methocel), povidone (polyvinylpyrrolidone).

[0448] Exemplary Therapeutic Agents In some embodiments, the therapeutic substance portion or layer of a device according to embodiments described herein comprises one or more therapeutic agents, such as one or more drugs and / or natural or synthetic compounds.

[0449] In some embodiments, the one or more therapeutic agents are in one or more of a solid form, a powder, an ointment, a liquid, beads (e.g., polymeric beads), a dispersion, a solution, pellets, microparticles, microspheres, and microcapsules.

[0450] In some embodiments, the therapeutic agent comprises one or more therapeutic agents as microparticles in the size range of 1-1000 μm.

[0451] In some embodiments, the therapeutic agent comprises an active pharmaceutical ingredient (API) and / or an excipient and / or a combination thereof.

[0452] In some embodiments, an ophthalmic device (e.g., according to one or more embodiments described herein) comprises one or more therapeutic agents at a dose in the range of about 1 μg to about 10,000 μg, or greater than 10,000 μg, or 0 to 1 μg, or 1 μg to 5 μg, or 5 μg to 10 μg, or 10 μg to 50 μg, or 50 μg to 100 μg, or 100 μg to 500 μg, or 500 μg to 1000 μg, or 1000 μg to 5000 μg, or 5000 μg to 10000 μg, or 10000 μg to 30000 μg.

[0453] In some other embodiments, an ophthalmic device (e.g., according to one or more embodiments described herein) comprises a therapeutic agent in a mass of about 1 microgram to about 20 milligrams. In some embodiments, the mass of the therapeutic agent is about 1 nanogram, or about 2 nanograms, or about 3 nanograms, or about 4 nanograms, or about 5 nanograms, or about 6 nanograms, or about 7 nanograms, or about 8 nanograms, or about 9 nanograms, or about 10 nanograms, or about 11 nanograms, or about 12 nanograms, or about 13 nanograms, or about 14 nanograms, or about 15 nanograms, or about 20 nanograms, or about 30 nanograms, or about 40 nanograms, or about 50 nanograms, or about 60 nanograms, or about 70 nanograms, or about 80 nanograms, or about 90 nanograms, or About 100 nanograms, or about 200 nanograms, or about 300 nanograms, or about 400 nanograms, or about 500 nanograms, or about 600 nanograms, or about 700 nanograms, or about 800 nanograms, or about 900 nanograms, or about 1 milligram, or about 2 milligrams, or about 3 milligrams, or about 4 milligrams, or about 5 milligrams, or about 6 milligrams, or about 7 milligrams, or about 8 milligrams, or about 9 milligrams, or about 10 milligrams, or about 12 milligrams, or about 14 milligrams, or about 16 milligrams, or about 18 milligrams, or about 20 milligrams.

[0454] In some embodiments, the device is about 0.1% to about 99.5%, or about 0.5% to about 90%, drug-releasing material, which is combined with, for example, a pharmaceutically acceptable carrier material(s).

[0455] In some embodiments, the therapeutic agent concentration in the device is less than 0.01%, or between 0.01% and 0.1%, or between 0.1% and 1%, or between 1% and 5%, or between 5% and 10%, or between 10% and 30%, or between 30% and 60%, or between 60% and 90%, or between 90% and 100%.

[0456] In some embodiments, the ophthalmic device (e.g., therapeutic substance layer and / or therapeutic substance region) comprises one or more of the following therapeutic agents (also referred to herein as "therapeutic components"): Aflibercept, atropine, bevacizumab, brimonidine / timolol, cyclosporine, ciprofloxacin, cyclopentolate, diisopropyl fluorophosphate, diquafosol, dorzolamide / timolol, echothiophate, latanoprost / timolol, latanoprost enox, lifitegrast Loteprednol, fluocinolone, fluorometholone, difluprednate, prednisolone, triamcinolone, rimexolone Mydriatics and cycloplegics, nandrolone sulfate, naphazoline / Pheniramine, nedocromil, netarsudil, ofloxacin, pegaptanib, pilocarpine, pirenoxine, ranibizumab, ripasudil, tauroursodeoxycholic acid, tabilermide, tropicamide / hydroxyamphetamine, verteporfin Axar, bevacizumab, cefazolin, ceftazidime, cocaine, EDTA, gatifloxacin, gentamicin, idoxuridine, Iluvien®, indocyanine green, infliximab, interferon, intravitreal injection, iohexol, ipamidol, iopamidol-M, lissamine green, membrane blue, mitomycin, moxifloxacin, rituximab, serum eye drops, disposable povidone, subconjunctival injection, tetracaine PF, tobramycin, TPA, vancomycin Cyclopentolate, phenylephrine, proparacaine, steroids, tropicamide Amikacin, amphotericin B, dexamethasone, mitomycin Small molecules, biologics, autoimmune drugs, anti-cancer and / or anti-cancer drugs, anti-inflammatory drugs, anti-infective drugs, antibiotics, cannabidiol ·Synthetic compounds ·Natural compounds Drug: In some embodiments, hydrophilic or hydrophobic. Formulation: In some embodiments, hydrophilic or hydrophobic. Excipients, including: anti-adherents, binders, coating agents, colorants, disintegrants, flavorings, glidants, lubricants, preservatives, adsorbents, sweeteners, and colorants.

[0457] In some embodiments, the therapeutic agent includes an enhancer agent, for example, for penetration enhancement and / or membrane pore opening.

[0458] In some embodiments, the therapeutic agent includes an agent that enhances solubility in human body fluids (including serum and / or blood).

[0459] In some embodiments, therapeutic agents include agents that activate and / or inhibit processes in the body.

[0460] In some embodiments, the therapeutic agent includes a prodrug form of another drug.

[0461] In some embodiments, the therapeutic agent includes a biosimilar form of another drug.

[0462] The therapeutic agent, in some embodiments, is administered in any dosage form, including modified release dosage forms, including immediate release dosages, delayed release dosages, extended release dosages, sustained release dosages, stimulus-triggered release dosages, and / or targeted release dosages.

[0463] Modified release dosing techniques, in some embodiments, use any of the following release techniques: diffusion, dissolution, osmosis, ion exchange resins, suspension, bioadhesion, matrix, and the like.

[0464] Processes for modified release formulations include microencapsulation, molecularly imprinted polymers (MIPs), and 3D drug printing.

[0465] The therapeutic agent, in some embodiments, is any formulation containing optional excipients and other available compounds.

[0466] Exemplary Nanoparticle and / or Microparticle Therapeutic Agent(s) In some embodiments, the therapeutic agent portion or layer of the device (e.g., according to one or more embodiments described herein) comprises one or more therapeutic agents in the form of nanoparticles and / or microparticles. In some embodiments, the nanoparticle and / or microparticle therapeutic agent(s) are coated with and / or include mucoadhesive compounds and / or polymer(s). In some embodiments, coating the particle(s) increases the residence time of the particle(s) and / or the duration of drug elution of the particle(s).

[0467] For example, atropine microparticles can be mentioned.

[0468] For example, atropine sulfate in albumin-chitosan microparticles may include one or more features described, for example, in "Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery" by Richard T Addo et al, J Pharm Sci. 2015 May;104(5):1677-90, the entirety of which is incorporated herein by reference.

[0469] In some embodiments, the microparticles have an average size of about 2 microns, a 10% atropine concentration, and a release time of about 50 hours. These particles, in some embodiments, are surface coated with an additional polymer(s) having one or more different properties, and in some embodiments, achieve a cumulative, prolonged release pattern over 7 days or more.

[0470] For example, the microparticles may include one or more features described in "Development of Water-Compatible Molecularly Imprinted Polymers Based on Functionalized β-Cyclodextrin for Controlled Release of Atropine" by Yahui He et al., Polymers 2020, 12(1), 130, the entirety of which is incorporated herein by reference.

[0471] For example, timolol nanoparticles can be mentioned.

[0472] For example, the particles may include one or more features described in "Chitosan nanoparticles for prolonged delivery of timolol maleate" by Sunil A Agnihotri 1, Tejraj M Aminabhavi, Drug Dev Ind Pharm. 2007 Nov;33(11):1254-62, the entirety of which is incorporated herein by reference.

[0473] In some embodiments, the particles have an average particle size ranging from 118 to 203 nm, while in some embodiments, the zeta potential ranges from +17 to +22 mV. In some embodiments, the encapsulation efficiency of the nanoparticles ranges from 47.6 to 63.0%. In some embodiments, based on the results of in vivo release studies conducted, for example, in phosphate buffered saline at pH 7.4, the release of timolol maleate is slow, lasting, for example, up to 24 hours. In some embodiments, the particles are surface coated, for example, with additional polymer(s) having different properties, to achieve a cumulative, prolonged release pattern over 7 days or more.

[0474] For example, the timolol microparticles may comprise one or more of the features described in "Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid) / poly(lactic acid) microspheres for over 3 months" by James P Bertram 1, Sandeep S Saluja, Jodi McKain, Erin B Lavik, J Microencapsul. 2009 Feb;26(1):26, the entirety of which is incorporated herein by reference.

[0475] In some embodiments, the microspheres are manufactured using a 50:50 blend of PLGA 502H and PLA. In some embodiments, the microspheres deliver timolol maleate for 50-200 days, or 50-150 days, or 90-120 days, or about 107 days.

[0476] 68A-68B are simplified schematic cross-sectional illustrations of a device 6800 on the surface of an eye 6804, according to some embodiments of the present invention.

[0477] For simplicity, device 6800 is shown as having a rectangular cross-section, however, in some embodiments, device 6800 has a shape having one or more features of the device(s) described elsewhere herein (e.g., a shape including a curved rear device surface and / or a curved front device surface).

[0478] In some embodiments, device 6800 includes layer 6812 containing therapeutic agent particles 6836, which in some embodiments include one or more characteristics of microparticles and / or nanoparticles, for example, as described elsewhere herein. In some embodiments, other materials in layer 6812 are rapidly dissolvable and / or degradable and / or erodible. Erosion, in some embodiments, exposes particles 6836 and allows dispersion of particles 6836, as shown, for example, in the transitions in FIGS. 68A-68B.

[0479] In some embodiments, particles 6836 comprise a therapeutic substance. Optionally, in some embodiments, particles 6836 comprise a mucoadhesive material. Potentially, once the particles are released from layer 6812 and contact the ocular surface 6804 (e.g., due to movement(s) of one or more of the eyelid, eyeball, and tear fluid), the particles adhere to the ocular surface. In some embodiments, the particles adhere to one or more mucosal surfaces, including, for example, the eyeball and / or eyelid. In some embodiments, the particles then degrade (e.g., over about 10 minutes, or about 1 hour, or about 12 hours, or about 1 day, or about 3 days, or over a shorter, longer, or intermediate duration) and release the therapeutic substance to the ocular tissue.

[0480] Optionally, in some embodiments, the device includes one or more additional layers (e.g., layers other than layer 6812). For example, in some embodiments, device 6800 includes mucoadhesive layer 6810.

[0481] In some embodiments, the particle-containing therapeutic substance layer 6812 is incorporated into one or more of the device embodiments described within this document, including, for example, covering and / or access features for the therapeutic substance layer 6812.

[0482] Exemplary Fabrication of Exemplary Devices In some embodiments, the device manufacturing process and / or film manufacturing process comprises a multilayer casting process and / or one or more industrial processes, such as, for example, spraying, dipping, coating, brushing, extruding, injecting, electrospinning, pressing, cutting, drilling, 3D printing, 3D engraving, laser cutting, heating, laser heating, chemical etching, chemical bonding, adhesive bonding, and the like.

[0483] In some embodiments, the device and / or portion(s) of the device are formed by one or more of adhesive bonding, blowing, casting, extruding, coating, laminating, welding, pressing, spinning, chemical reaction, spraying, dipping, coating, brushing, extruding, injecting, electrospinning, pressing, cutting, 3D printing, 3D engraving, laser cutting, heating, laser heating, chemical etching, chemical bonding, adhesive bonding, and any combination thereof.

[0484] FIG. 69 illustrates an ophthalmic device manufacturing method according to some embodiments of the present invention.

[0485] At 6900, in some embodiments, a film is received. For example, a multilayer film is received. In some embodiments, the film is manufactured, for example, according to one or more features shown in and / or described with respect to FIG. 70 and / or according to one or more features described with respect to Film Examples 1-55.

[0486] At 6902, in some embodiments, the film is formed, for example, using one or more methods.

[0487] At this time, when the film is in a dry or wet state, in some embodiments, the film is engineered to have a selected thickness profile and / or curvature, and / or to add one or more features, such as one or more protrusions, cavities, apertures, holes, slices, etc. For example, in some embodiments, the device has at least one aperture that is mechanically and / or chemically formed.

[0488] In some embodiments, forming includes one or more treatments, such as applying mechanical force (e.g., pressing), heating and / or heat treatment, exposure to one or more chemicals, or treatment with one or more electrical processes. In some embodiments, multiple treatments are applied sequentially, while in some embodiments, multiple treatments are applied simultaneously (e.g., simultaneous application of heat and mechanical force). In some embodiments, one or more types of treatments include the use of a jig.

[0489] In some embodiments, the film is shaped, for example, by cutting by one or more of mechanical and chemical means, for example, by using one or more of a cutting tool (e.g., scissors, knife), stamping, or a laser.

[0490] At 6904, optionally, in some embodiments, one or more additional materials and / or layers are added to the film.

[0491] At 6906, optionally, in some embodiments, the film is cut to create one or more individual ophthalmic devices. For example, a single film portion may be used to provide multiple ophthalmic devices. In some embodiments, cutting is accomplished by one or more of mechanical and chemical means. For example, cutting may be accomplished by one or more of a cutting instrument (e.g., scissors, knife), stamping, or a laser.

[0492] At 6908, in some embodiments, the device is molded, for example, according to one or more of the features described with respect to step 6902.

[0493] At 6910, in some embodiments, optionally, in some embodiments, one or more additional materials and / or additional layers are added to the device and / or portions of the device, for example, in some embodiments, material is added to the periphery and / or edge region(s) of the device.

[0494] At 6912, in some embodiments, the device is optionally shaped, for example, shaped according to one or more of the features described with respect to step 6902.

[0495] At 6914, in some embodiments, the device (and / or the completed device) is packaged, for example, in a single-device package and / or a multi-device package. In some embodiments, the device is packaged in a kit, which in some embodiments includes one or more devices and one or more of an insertion tool for administering the device and / or to the subject's eye, additional agent(s), and / or additional formulation(s).

[0496] The device, in some embodiments, is packaged attached to an insertion tool, potentially increasing one or more of the safety and ease of applying the device to a subject's eye.

[0497] In some embodiments, the insertion tool has a cup shape (e.g., a thimble shape) and includes a surface for the device, e.g., in some embodiments, the device is placed into the opening of the cup shape. At this time, in some embodiments, the cup shape is flexible, and squeezing the cup shape urges the device toward the surface to which it is desired to attach. In some embodiments, the insertion tool is an elongated thimble shape with any other portion(s).

[0498] In some embodiments, the device is kept wet at the end of the manufacturing process, e.g., packaged in a hydrated state. Alternatively, in some embodiments, the device may be dried. In some embodiments, the device is packaged (e.g., after drying) in a dry and / or semi-hydrated state.

[0499] At 6916, in some embodiments, the device is sterilized, for example, using one or more of gamma radiation, ETO, and steam.

[0500] In some embodiments, the order of steps 6914 and 6916 is reversed.

[0501] Device Fabrication Example 1 In some embodiments, the film (e.g., according to one or more features described and / or shown with respect to the film elsewhere herein) is cut into a desired shape (e.g., a shape that includes one or more features of one or more of the shapes of the drawings), for example, using a punch. In some embodiments, the film is then cut into a disk shape.

[0502] In some embodiments, a shape (e.g., a disk) is inserted into a mold and pressed so that the front and / or back surfaces of the disk conform to the desired curvature, which, for example, in some embodiments includes molding the edges of the device to the desired edge shape.

[0503] In some embodiments, excess material is removed (eg, by laser cutting) and / or the edge(s) of the device are smoothed.

[0504] In some embodiments, the device is then packaged and / or sent for sterilization.

[0505] Device Fabrication Example 2 In some embodiments, the film (e.g., according to one or more features described and / or illustrated with respect to the film elsewhere herein) is shaped, e.g., formed using a mold, in some embodiments, by applying pressure and / or heat to the film to cause it to conform to the mold, e.g., to form the inner and outer curvature and / or desired edge shape of the device.

[0506] In some embodiments, the formed film is laser cut, for example into an oval shape.

[0507] In some embodiments, excess material is removed (eg, by laser cutting) and / or the edge(s) of the device are smoothed.

[0508] In some embodiments, the device is then packaged and / or sent for sterilization.

[0509] Device Fabrication Example 3 Using the final device of "Device Fabrication Example 2," additional material is added to the periphery (eg, edge region) of the device, eg, to provide desired edge characteristics, eg, shape and / or material composition.

[0510] In some embodiments, the device is then packaged and / or sent for sterilization.

[0511] Device Fabrication Example 4 In some embodiments, a film (e.g., according to one or more of the features described and / or illustrated with respect to films elsewhere herein) is provided, in some embodiments, a tunnel(s) is cut through and / or a cavity(ies) and / or a hole(s) is / are cut and / or created and / or drilled in the lubricating film layer.

[0512] In some embodiments, the film is then cut into disk shapes, for example, using a punch.

[0513] In some embodiments, the film is shaped, e.g., formed using a mold, in which, in some embodiments, pressure and / or heat is applied to the film to cause it to conform to the mold, forming, e.g., the inner and outer curvatures and / or desired edge shapes of the device on the film.

[0514] In some embodiments, excess material is removed (eg, by laser cutting) and / or the edge(s) of the device are smoothed.

[0515] In some embodiments, the device is then packaged and / or sent for sterilization.

[0516] Device Fabrication Example 5 In some embodiments, a film (e.g., according to one or more of the features described and / or illustrated with respect to films elsewhere herein) is provided, in some embodiments, a tunnel(s) is cut through and / or a cavity(ies) and / or a hole(s) is / are cut and / or created and / or punched in the mucoadhesive film layer.

[0517] In some embodiments, the film is then cut into disk shapes, for example, using a punch.

[0518] In some embodiments, the film is shaped, e.g., formed using a mold, in which, in some embodiments, pressure and / or heat is applied to the film to cause it to conform to the mold, forming, e.g., the inner and outer curvatures and / or desired edge shapes of the device on the film.

[0519] In some embodiments, excess material is removed (eg, by laser cutting) and / or the edge(s) of the device are smoothed.

[0520] In some embodiments, the device is then packaged and / or sent for sterilization.

[0521] Device Fabrication Example 6 The fabrication of the device is based on pre-fabricated films according to the above description, followed by additional processing.

[0522] In some embodiments, the film is cut into a disc shape, for example using laser cutting.

[0523] In some embodiments, the disc-shaped film portion is formed, e.g., using a mold, in which, in some embodiments, pressure and / or heat is applied to the film to cause the film to conform to the mold, e.g., to form the inner and outer curvatures and / or desired edge shapes of the device on the film.

[0524] In some embodiments, the device is coupled to a dispensing tool and / or an insertion tool.

[0525] In some embodiments, the device is then packaged and / or sent for sterilization.

[0526] In some embodiments, one or more additional processes, such as adding layer(s) and / or adding therapeutic agent(s) and / or adding compounds, are performed on one or more of the devices of Device Manufacturing Examples 1-5, for example, prior to packaging and / or sterilization.

[0527] FIG. 70 illustrates a method of manufacturing a film, according to some embodiments of the present invention.

[0528] At 7000, in some embodiments, a first solution is cast onto a support sheet.

[0529] In some embodiments, the first solution comprises a mucoadhesive material, e.g., after casting, the mucoadhesive material forms a mucoadhesive first layer. Optionally, in some embodiments, the mucoadhesive solution (and / or mucoadhesive layer) comprises a therapeutic agent(s). Alternatively or additionally, in some embodiments, after casting of the first solution, the therapeutic agent(s) are applied to the cast surface (before and / or after the surface has dried).

[0530] In some embodiments, the first solution includes a lubricious material, e.g., after casting, the lubricious material forms a lubricious first layer. Optionally, in some embodiments, the lubricious solution (and / or lubricious layer) includes a therapeutic agent(s). Alternatively or additionally, in some embodiments, after casting the first solution, a therapeutic agent(s) is / are applied to the cast surface (before and / or after the surface has dried).

[0531] In some embodiments, the first solution does not include a lubricating material or a mucoadhesive material. In some embodiments, the first solution includes a therapeutic substance and / or a therapeutic agent(s) is / are applied to the surface of the first layer formed by casting the first solution.

[0532] At 7002, optionally, in some embodiments, the first layer is treated.

[0533] For example, if the first layer has mucoadhesive properties, the surface of the first layer is imparted with lubricious material properties, where the treatment may include, for example, one or more chemical processes and / or material deposition.

[0534] For example, if the first layer has lubricious properties, the surface of the first layer may be imparted with mucoadhesive material properties, where the treatment may include, for example, one or more chemical processes (e.g., plasma treatment) and / or material deposition (e.g., addition of an adhesive agent).

[0535] In some embodiments, the first layer is treated to impart both lubricious properties (e.g., on one side) and mucoadhesive properties (e.g., on the opposite side), e.g., when the first layer has neither a mucoadhesive nor a lubricious material.

[0536] At 7004, optionally, in some embodiments, an additional material (e.g., a film) is applied to the first surface. For example, the first surface is coated. For example, portions of the first surface are coated, e.g., with a pattern, e.g., to provide portion(s) of the ultimately manufactured device with a multilayer film having portion(s) of additional material at specific location(s). In some embodiments, the additional material is applied before the first layer is completely dry. Alternatively, in some embodiments, the additional material is applied to the dried first layer.

[0537] At 7006, optionally, in some embodiments, additives are attached to the first layer, for example, by adhesive and / or adhesive welding, and / or by chemical and / or physical means.

[0538] At 7008, optionally, in some embodiments, the film is engineered, for example, to shape the film. For example, this may include one or more features of step 6902 of FIG. 69.

[0539] At 7010, optionally, in some embodiments, a second solution is cast onto the film surface to form a second layer, where in some embodiments, if the first layer comprises a mucoadhesive material, the second layer comprises intermediate layer feature(s) and / or material(s) (e.g., as described elsewhere herein) and / or lubricious layer material (e.g., as described elsewhere herein).

[0540] At 7012, optionally, in some embodiments, the second layer may be dried.

[0541] At 7014, optionally, in some embodiments, the film is engineered, for example, to shape the film. For example, this may include one or more features of step 6902 of FIG. 69.

[0542] In some embodiments, additional layers are cast onto the film, for example, after one or more of the method steps.

[0543] 71A-71D are simplified schematic cross-sectional views of films according to some embodiments of the present invention.

[0544] In some embodiments, Figures 71A-71D show cross-sectional views of a portion of a device.

[0545] In some embodiments, Figures 71A-71D illustrate different, eg, successive, portions of a manufacturing process according to some embodiments of the present invention.

[0546] FIG. 72 illustrates a method of manufacture according to some embodiments of the present invention.

[0547] 71A, in some embodiments, the substrate layer 7174 is a film, which may include one or more features of a film, e.g., as described elsewhere herein. For example, in some embodiments, the film includes a single layer. For example, in some embodiments, the film includes multiple layers, e.g., each layer having a different composition and / or material properties.

[0548] 71B, in some embodiments, cavity(ies) are created in the base layer 7174. For example, the cavity(ies) may be created by and / or using one or more of a jig, a press, a punch, laser engraving, drilling, molecularly imprinted polymer (MIP), or 3D printing.

[0549] In step 7202 of FIG. 72, for example, referring to FIG. 71C, in some embodiments, the cavity(ies) are filled with a material 7178 that is different from the material of the base layer 7174, for example.

[0550] 72D, in some embodiments, one or more additional layers 7180 are added on top of the base layer 7174. In some embodiments, the additional layer 7180 has different properties (e.g., different material properties) than the other portion(s) 7174, 7178.

[0551] In some embodiments, the base layer 7174 comprises a mucoadhesive material, the filler material 7178 comprises a therapeutic substance, and the additional layer 7180 comprises a lubricious material.

[0552] 73A-73D are simplified schematic cross-sectional views of films according to some embodiments of the present invention.

[0553] 73E-73F are simplified schematic cross-sectional views of devices according to some embodiments of the present invention.

[0554] In some embodiments, Figures 71A-71D illustrate different portions of a manufacturing process according to some embodiments of the present invention, such as a sequence of portions transitioning in time from Figures 71A-71B-71C-71D.

[0555] Referring to FIG. 73A, in some embodiments, a film 7374 is provided, which may be a film including one or more features described with respect to films and / or layers (e.g., in some embodiments, film 7374 is a first layer of one or more exemplary film manufacturing examples).

[0556] In some embodiments, the film 7374 is formed into the configuration shown in Figure 73B, where the forming includes, for example, one or more features of step 6902 of Figure 69.

[0557] Referring to FIG. 73C, in some embodiments, additional material 7378 is added to the formed film 7374, e.g., cast onto the formed film, which may include, for example, one or more of the features described with respect to step 6904 of FIG. 69.

[0558] Referring to FIG. 73D, in some embodiments, a film including two layers 7374, 7378 is formed, where the forming includes, for example, one or more features of step 6902 of FIG.

[0559] 73D, in some embodiments, the film is cut into individual devices 7300, for example, along the dotted lines shown in FIG. 73D. In some embodiments, the cutting includes one or more features of step 6906 of FIG.

[0560] 73F, in some embodiments, device 7300 is molded, e.g., additional features 7382 are formed in device 7300. For example, this may include one or more of the features described in step 6902 of FIG. 69. For example, one or more cavities 7382 are formed. At this time, in some embodiments, the cavity(ies) are then filled with additional material (e.g., this may include one or more of the features shown in and / or described in connection with FIGS. 71B-71D).

[0561] 74A-74C are simplified schematic cross-sectional views of a device 7400, according to some embodiments of the present invention.

[0562] In some embodiments, the device 7400 includes a first layer 7410 and a second layer 7412. In some embodiments, the device rear surface 7416 is concave. In some embodiments, the concave surface is filled with an additional material 7436, e.g., at the time of manufacture and / or by a user, e.g., immediately prior to use. In some embodiments, the additional material 7436 includes a therapeutic ingredient(s). In some embodiments, the additional material 7436 includes a mucoadhesive. In some embodiments, the device 7400 is used to extend the residence time of a topical application in contact with the eye, e.g., the device 7400 sealingly adheres to the ocular surface 7404 and the additional material 7436 remains in contact with the ocular surface for a period of time, e.g., in some embodiments, longer than the residence time of, e.g., eye drops and / or ointments. In some embodiments, the period is from 10 minutes to 12 hours, or from 10 minutes to 2 hours, or shorter, or longer, or any intermediate duration or range.

[0563] In some embodiments, the device 7400 comprises a lubricious material 7412 and / or a mucoadhesive material 7410 .

[0564] Exemplary Manufacturing of Exemplary Films In some embodiments, the film is produced by casting two or three layers, for example, by coating solutions of each layer sequentially, for example, onto a support surface (e.g., a support sheet).

[0565] The support sheet, in some embodiments, is flat or curved in shape and / or includes pattern(s), such as, for example, cavity(ies) and / or bulge(s).

[0566] The support sheet, in some embodiments, is a film and / or substrate. Exemplary support sheet materials include Teflon film, Teflon-coated substrate, silicone film, silicone substrate and / or silicone-coated substrate, PET (polyethylene terephthalate) film, BoPET film, Melinex, MYLAR-A, Hostaphan, Kapton (polyimide) film, and combinations thereof. In some embodiments, the support sheet material is selected to allow the first layer to be cast onto the substrate without the need for lubricating and / or adhesive materials.

[0567] In some embodiments, the first layer of the device (e.g., a lubricious layer) is cast onto a substrate surface, optionally followed by one or more intermediate layers, which in some embodiments is followed by a mucoadhesive layer.

[0568] In some embodiments, one or more portions of a separately manufactured (eg, pre-made) film are added, eg, to form a layer.

[0569] In some embodiments, the order in which the layers are cast is reversed, e.g., the mucoadhesive layer is cast first, followed by the optional intermediate layer(s), and then, in some embodiments, the lubricious layer.

[0570] In some embodiments, for example, instead of casting, one or more of the layers are applied to the previous layer(s) and / or support by one or more of extrusion, injection, injection molding, plating, vapor deposition, Langmuir-Blodgett techniques, spin coating, and dip coating.

[0571] In some embodiments, one or more prefabricated film and / or partial (e.g., particle, such as microparticle and / or nanoparticle) parts are incorporated into the device, e.g., as part of the casting of the solution and / or formulation and / or between the cast layers.

[0572] In some embodiments, one or more layers (eg, each layer) may be dried before casting the next layer.

[0573] Exemplary Solution In some embodiments, the CA:TEC solution comprises cellulose acetate:TEC, TEC, acetone, and optionally dye(s) and / or colorant(s).

[0574] In some embodiments, the CA:TEC solution is made by first dissolving cellulose acetate in acetone, followed by the addition of the TEC solution and, optionally, the dye(s) and / or colorant(s).

[0575] In some embodiments, the Klucel solution comprises Klucel, water, ethanol, and optionally dye(s) and / or colorant(s).

[0576] In some embodiments, a Klucel solution is made by dissolving Klucel powder in water and ethanol, and then optionally adding dye(s) and / or colorant(s).

[0577] In some embodiments, the Kollicoat solution comprises Kollicoat and ethanol.

[0578] In some embodiments, the Kollicoat solution is made by dissolving Kollicoat in ethanol.

[0579] In some embodiments, the Klucel / 974 / loteprednol solution comprises Klucel, Carbomer 974, loteprednol, and ethanol.

[0580] In some embodiments, the Klucel / 974 / loteprednol solution is made by dissolving Klucel powder in ethanol, then adding Carbomer 974 to the solution, and then adding loteprednol to the solution.

[0581] In some embodiments, the Klucel / diclofenac solution comprises Klucel, diclofenac, and ethanol.

[0582] In some embodiments, the Klucel / diclofenac solution is made by dissolving Klucel powder in ethanol and then adding diclofenac to the solution.

[0583] In some embodiments, the ethylcellulose:PEG solution comprises ethylcellulose, acetone / ethanol, and a PEG solution.

[0584] In some embodiments, the ethylcellulose:PEG solution is made by dissolving ethylcellulose in acetone / ethanol, followed by adding the PEG solution.

[0585] The materials in the above examples may be substituted for any of the other materials mentioned elsewhere in this specification.

[0586] In some embodiments, for example, the materials used in device fabrication are biocompatible and / or become biocompatible upon drying and / or processing.

[0587] In some embodiments, for example, the materials used in the device are selected from the following: Hydroxypropyl cellulose (HPC) Hydroxypropyl methylcellulose (HPMC) Carboxymethyl cellulose (CMC) Polyvinyl alcohol (PVOH) Polyethylene glycol (PEG) Cellulose acetate (CA) Polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat) Polyacrylic acid (e.g., Carbopol or Carbomer) Polyacrylic acid (e.g., Carbopol or Carbomer) hyaluronic acid Ethyl cellulose (EC) Triethyl citrate (TEC) glycerol Dextran A combination of these

[0588] In some embodiments, the device is constructed from a single material, such as from the previous list, whereby different layers and / or different material properties are created, in some embodiments, by utilizing grades of material and / or by processing the material in one or more ways, such as chemically and / or mechanically, and / or by heating and / or cooling.

[0589] Other examples of solutions include PVOH:PEG:glycerol, or PVOH:PEG:HPMC, or PVOH:HPC, or PVOH:Kollicoat:glycerol, or PVOH:Kollicoat:glycerol:CMC.

[0590] In some embodiments, the materials include any form, structure, formulation, derivative, combination, and / or variation and / or salt of the described material(s).

[0591] In some embodiments, additional materials are used to adjust and / or modify the property(ies) of the materials used and / or to obtain a device with selected properties (e.g., properties described herein).

[0592] Exemplary Therapeutic Agent(s) In some embodiments, the therapeutic agent(s) are added to the solution and / or placed on top of the dry layer, in some embodiments, the therapeutic agent is in the form of one or more solids (flat sheets, curved sheets, circular sheets, oval sheets, ring shapes, spheres, rods, bars), powders, ointments, liquids, beads, dispersions, solutions, pellets, microparticles, nanoparticles, microspheres, and microcapsules, liposomes, lysosomes, micelles, and reverse micelles.

[0593] Film Example 1 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0594] A Klucel solution can be cast as a second layer onto the dried CA:TEC first layer and then dried.

[0595] Film Example 2 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0596] A therapeutic agent is added to the Klucel solution, and the resulting Klucel solution can be cast onto the dried CA:TEC first layer film to form a second layer, which can then be dried.

[0597] Film Example 3 One or more therapeutic agents are added to the CA:TEC solution, and the resulting solution can be cast as a first layer onto a support sheet and allowed to dry.

[0598] A therapeutic agent is added to the Klucel solution, and the resulting solution is cast onto the dried CA:TEC first layer film to form a second layer and allowed to dry.

[0599] Film Example 4 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0600] A therapeutic agent is added to the dried layer in some embodiments.

[0601] In some embodiments, the therapeutic agent is attached to the layer by an adhesive, by adhesive welding, and / or by chemical and / or physical means.

[0602] In some embodiments, the film is shaped to hold the therapeutic agent, for example, by molding one or more cavities and / or protrusions. The cavity(ies) and / or protrusion(s) are created in some embodiments by one or more of a jig, a press, a punch, laser engraving, drilling, molecularly imprinted polymers (MIPs), and 3D printing.

[0603] One or more therapeutic agents are added to the Klucel solution.

[0604] The Klucel solution can be cast as a second layer onto the dried CA:TEC (first layer) film and allowed to dry.

[0605] Film Example 5 One or more therapeutic agents are added to the CA:TEC solution, and the resulting solution can be cast as a first layer onto a support sheet and allowed to dry.

[0606] One or more therapeutic agents are added to the Klucel solution, and the resulting solution can be cast as a second layer onto the dried CA:TEC layer and then dried.

[0607] Optionally, the bilayer film is then molded, for example, to have one or more cavities and / or protrusions, for example, by jigs, presses, punches, laser engraving, drilling, molecularly imprinted polymers (MIPs), or 3D printing.

[0608] One or more therapeutic agents are added to the dried Klucel layer, at which point the shape of the film (e.g., the shape of the film imparted by a previous molding) configures the film to retain the therapeutic agent(s). For example, in some embodiments, the cavity(ies) retain the therapeutic agent(s).

[0609] Optionally, a therapeutic agent is attached, for example, by chemical attachment method(s) and / or physical (eg, welding) attachment method(s).

[0610] The Klucel solution can then be cast to form the third layer and then dried.

[0611] Film Example 6 The Kollicoat solution can be cast as a first layer onto a support sheet and allowed to dry.

[0612] The CA:TEC solution can be cast as a second layer onto the first layer of dried Kollicoat and then dried.

[0613] The Klucel solution can be cast as a third layer onto the dried second layer of CA:TEC and then dried.

[0614] Film Example 7 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0615] In some embodiments, the resulting CA:TEC film is shaped, for example, to define a selected thickness profile and / or curvature and / or other features, such as protrusions, cavities, apertures, holes, slices.

[0616] The Klucel solution can be cast as a second layer onto the dried CA:TEC first layer and then dried.

[0617] In some embodiments, the film shape is engineered, for example, to have a selected thickness profile and / or curvature, and / or to introduce feature(s), such as one or more protrusion(s), cavity(ies), aperture(s), hole(s), slice(s), etc.

[0618] Film Example 8 The CA:TEC solution is cast as a first layer onto a support sheet.

[0619] In some embodiments, after and / or before the first layer has dried, a layer of pre-made film and / or portions of the first layer are applied (e.g., in a pattern) to an area(s) of the first layer.

[0620] In some embodiments, the film is subjected to one or more procedures to adhere it to the first layer of CA:TEC, such as one or more of gluing, heating, and pressing.

[0621] A solution of Klucel can then be cast onto the film and then dried.

[0622] Film Example 9 The surface of the support sheet and / or parts of the surface of the support sheet are covered with a pre-formed film or parts of a film (eg, in a particular pattern).

[0623] Optionally, in some embodiments, the surface is then treated to adhere the pre-formed film, for example, using one or more of adhesive, heat, and pressing.

[0624] The CA:TEC solution can be cast onto the support sheet and pre-made film layer and allowed to dry.

[0625] Optionally, in some embodiments, the surface is then treated to adhere the pre-formed film, for example, using one or more of adhesive, heat, and pressing.

[0626] The Klucel solution can be cast onto the dried CA:TEC (first layer) film and allowed to dry.

[0627] Film Example 10 The production of the film is based on the preparation of a solution, followed by two casting processes.

[0628] The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0629] The Klucel / 974 / loteprednol solution can be cast as a second layer onto the dried CA:TEC (first layer) film and allowed to dry.

[0630] Film Example 11 The production of the film is based on the preparation of a solution, followed by two casting processes.

[0631] The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0632] Ciprofloxacin dissolved in acetic acid is added to the Klucel / 974 / ciprofloxacin solution.

[0633] The Klucel / 974 / ciprofloxacin solution can be cast as a second layer onto the dried CA:TEC (first layer) film and allowed to dry.

[0634] Film Example 12 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0635] The Klucel / diclofenac solution can be cast as a second layer onto the dried CA:TEC (first layer) film and allowed to dry.

[0636] Film Example 13 The ethylcellulose:PEG solution can be cast as a first layer onto a support sheet and allowed to dry.

[0637] The Klucel solution can be cast as a second layer onto the dried ethylcellulose:PEG (first layer) film and allowed to dry.

[0638] Film Example 14 An ethylcellulose:PEG / ibuprofen solution is made by dissolving ethylcellulose (EC) in acetone / ethanol, then adding the PEG solution, followed by the ibuprofen.

[0639] In EC:PEG / ibuprofen casting, the EC:PEG / ibuprofen solution is cast as a first layer onto a support sheet and allowed to dry.

[0640] The Klucel solution can be cast as a second layer onto the dried EC:PEG / ibuprofen (first layer) film and allowed to dry.

[0641] Film Example 15 The CA:TEC solution can be cast as a first layer onto a support sheet and allowed to dry.

[0642] Carboxymethylcellulose (CMC) solution is made by dissolving CMC powder in water, optionally with the addition of dyes and / or colorants.

[0643] The CMC solution can be cast as a second layer onto the dried CA:TEC (first layer) film and dried.

[0644] In some embodiments, an additional CMC layer is cast on top of the dried CMC layer.

[0645] General It is expected that numerous related ophthalmic treatments and / or ophthalmic devices and / or therapeutic compositions will be developed between the filing of this application and the expiration of the patent term, and the scope of the terms ophthalmic treatments and / or ophthalmic devices and / or therapeutic compositions is intended, a priori, to include all such new technologies.

[0646] The term "about" as used herein means ±20%.

[0647] The words "comprises," "comprising," "includes," "including," "having," and their conjugations mean "including, but not limited to."

[0648] The phrase "consisting of" means "including and limited to."

[0649] The phrase "consisting essentially of" means that the composition, method, or structure may include additional ingredients, steps, and / or components, but only if the additional ingredients, steps, and / or components do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0650] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the phrase "a compound" or "at least one compound" includes a plurality of compounds, including mixtures thereof.

[0651] Throughout this application, various embodiments of the invention are presented, in some embodiments, in 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 not only each individual numerical value within that range, but also all possible subranges. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed not only each individual numerical value within that range, e.g., 1, 2, 3, 4, 5, and 6, but also subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc. This is true regardless of the breadth of the range.

[0652] Whenever a numerical range is given herein, it is meant to include any recited number (fractional or integer) within the range given. The phrases "range(s) between" a first designated number and a second designated number and "range(s) from" a first designated number to a second designated number are used interchangeably herein and are meant to include the first designated number and the second designated number, and all fractional and integer numbers therebetween.

[0653] The term "method," as used herein, refers to ways, means, techniques, and procedures for accomplishing a given task, including, but not limited to, ways, means, techniques, and procedures that are known to or that can be readily developed from known ways, means, techniques, and procedures by those skilled in the art of chemistry, pharmacology, biology, biochemistry, and medicine.

[0654] The term "treating" as used herein includes arresting, substantially arresting, slowing, or reversing the progression of a condition, substantially ameliorating the clinical or cosmetic symptoms of a condition, or substantially preventing the appearance of clinical or cosmetic symptoms of a condition.

[0655] It will be understood 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 in any other described embodiment of the invention, as appropriate. Certain features described in the context of various embodiments should not be considered essential features of those embodiments, except to the extent that the embodiment is inoperable without those elements.

[0656] While the present 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.

[0657] It is intended by the applicant(s) that all publications, patents, and patent applications mentioned herein be incorporated by reference in their entireties, as if each individual publication, patent, and patent application was specifically and individually noted to be incorporated by reference herein. Furthermore, citation or identification of any reference in this application should 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. Additionally, any priority document(s) of this application are also incorporated by reference herein in their entireties.

Claims

1. The rear and The front and 1. An ophthalmic device comprising a body having: the size of the body, the shape of the posterior surface, and the shape of the anterior surface configure the device to reside on the bulbar conjunctiva of the eye; the device is configured to be hydrated in situ on the surface of the eye, the hydration of the device causing the device to expand 10% to 50% from its dry state dimensions; the rear surface has a concave surface, the radius of curvature of the concave surface being smaller than the radius of curvature of the bulbar conjunctiva, thereby causing suction to adhere the device to the bulbar conjunctiva; The device.

2. The device of claim 1 , wherein when resting on the bulbar conjunctiva, the posterior surface is adjacent to the bulbar conjunctiva and the anterior surface is at least periodically adjacent to the inner surface of the eyelid.

3. The device of claim 1 , wherein the body has a therapeutic substance and is configured to elute the therapeutic substance into the eye when the body resides on the bulbar conjunctiva.

4. The device of claim 3, wherein the body has a size of 2 to 8 mm.

5. The device of claim 4 , wherein the body has a thickness of less than 400 microns.

6. 6. The device of claim 5, wherein an edge region of the body less than 0.5 mm from the edge of the body has a thickness of less than 50 microns.

7. The device of claim 6 , wherein the rear surface is concave.

8. 8. The device of claim 7, wherein the ratio of the radius of curvature of the posterior surface to the radius of curvature of the sclera of the eye is greater than 0.

8.

9. The device of claim 7, wherein the radius of curvature of the posterior surface is between 9 and 11 mm.

10. The device of claim 7, wherein the elastic modulus of the device is 0.3 to 1.5 MPa.

11. The device of claim 7 , wherein the front surface is convex.

12. The device of claim 11 , wherein the radius of curvature of the anterior surface is less than the radius of curvature of the posterior surface.

13. 8. The device of claim 7, wherein the device is configured to remain on the ocular surface for at least 15 minutes.

14. 14. The device of claim 13, wherein the device is configured to rest on a portion of the bulbar conjunctiva, the portion residing between the cornea and the forniceal conjunctiva.

15. The device of claim 13 , wherein the device is configured to rest on a portion of the bulbar conjunctiva, the portion coinciding with a tear meniscus.

16. The device of claim 6 , wherein the posterior surface comprises a mucoadhesive material.

17. 17. The device of claim 16, wherein the front surface has a smooth surface and / or includes a lubricating material.

18. The device of claim 7 , wherein the body comprises a material that disintegrates in the eye.

19. The device of claim 7 , wherein the body comprises one or both of a biodegradable material and a bioerodible material.

20. The device of claim 6 , wherein the rear surface has one or more cavities.

21. The device of claim 6 , wherein the rear surface has one or more protrusions.

22. The device of claim 7 , wherein the device comprises one or more electronic elements.

23. The device of claim 7 , wherein the device is provided in a dry or semi-hydrated state.

24. The device of claim 7 , wherein the device is hydrated on the ocular surface.

25. The device of claim 7 , wherein the body has two or more layers with different material properties.

26. The body includes: Hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinyl alcohol (PVOH), polyethylene glycol (PEG), cellulose acetate (CA), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat), polyacrylic acid (e.g., Carbopol or Carbomer), hyaluronic acid, ethyl cellulose, triethyl citrate (TEC), glycerol, dextran, and combinations thereof; The device of claim 1 , comprising one or more of:

27. The device of claim 1 , wherein the device has one or more anchors configured to hold the device on the bulbar conjunctiva.

28. 28. The device of claim 27, wherein the anchor has a sharp edge on the body.

29. 30. The device of claim 28, wherein the edge has a radius of curvature of less than 100 microns.

30. 28. The device of claim 27, wherein the rear surface is roughened.

31. 1. An ophthalmic device comprising: a body configured to reside on a bulbar conjunctiva, the body comprising: The size is 2 to 8 mm, an edge region less than 0.5 mm from an edge of the body, the edge region having a thickness of less than 50 microns; and the device is configured to be hydrated in situ on the surface of the eye, the hydration of the device causing the device to expand 10% to 50% from its dry state dimensions; the rear surface of the body has a concave surface, and the radius of curvature of the concave surface is smaller than the radius of curvature of the bulbar conjunctiva, thereby causing suction to occur and attaching the device to the bulbar conjunctiva; The ophthalmic device.

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