Elastomeric matrices comprising polyvinyl alcohol

Abstract

The present invention relates to shaped polyvinyl alcohol (PVOH) based elastomeric matrixes for ophthalmic uses and, more particularly, but not exclusively, to such matrixes that are degradable.

Description

[0001] ELASTOMERIC MATRICES

[0002] RELATED APPLICATION / S

[0003] This application claims the benefit of priority of U.S. Provisional Patent Application Nos. 63 / 462,269 filed on April 27, 2023 and 63 / 463,034, filed on April 30, 2023, the contents of which are incorporated herein by reference in their entirety.

[0004] FIELD AND BACKGROUND OF THE INVENTION

[0005] The present invention, in some embodiments thereof, relates to shaped polyvinyl alcohol (PVOH) based elastomeric matrixes for ophthalmic uses and, more particularly, but not exclusively, to such matrixes that are biodegradable or bioerodible.

[0006] Polyvinyl alcohol (PVOH) is water-soluble synthetic polymer represented by the formula (C2H4O)n. It is prepared by hydrolysis of polyvinyl acetates, which replaces the acetate groups with hydroxyl groups. PVOH has numerous applications, including biomedical and pharmaceutical applications such as artificial heart linings, artificial cartilages, catheters, skin and pancreas membranes. PVOH may be chemically or physically (i.e., not by covalent bonds) crosslinked.

[0007] During physical crosslinking, hydroxyl groups interact to form intra- and intermolecular hydrogen bonds resulting in formation of crystallites. Physical crosslinking is typically carried out by freeze-thaw with or without addition of solvents, resulting in the well-known cryo gels. Alternatively, solutions of polyvinyl alcohol can be dried (Otsuka, E., & Suzuki, A., Journal of Applied Polymer Science, 2009, 114(1), 10-16, doi: 10.1002 / app.30546]. Various plasticizers can be added to improve flexibility, and the amount added is commonly less than 30 %, often less than 10 % [Mohsin, M., et al., Journal of Applied Polymer Science, 2011, 122(5), 3102-3109. doi: 10.1002 / app.34229; Lim, L. Y. et al., Drug Development and Industrial Pharmacy, 1994, 20(6), 1007-1020. doi: 10.3109 / 03639049409038347; and Wu, W. et al., Journal of Polymers and the Environment, 2011, 20(1), 63-69. doi:10.1007 / sl0924-011-0364-7],

[0008] Zhang, B. et al., [Ceramics International, 2020, doi: 10.1016 / j.ceramint.2020.03.286] teach about the instructive role of mechanical properties of polyvinyl alcohol film in the process of YSZ tape calendaring.

[0009] U.S. Patent No. US4874562 discloses a method of molding a polyvinyl alcohol contact lens.

[0010] U.S. Patent No. US4663358 discloses a porous and transparent hydrated gel that is prepared from a poly(vinyl alcohol) solution in a mixed solvent consisting of water and a water-miscible organic solvent. U.S. Patent No. US 10513588 discloses water-soluble polyvinyl alcohol film with plasticizer blend.

[0011] U.S. Patent No. US9724230 discloses a dry eye treatment apparatus and methods which generally includes a patch or strip affixed to the skin of the upper and / or lower eyelids.

[0012] U.S. Patent No. US5137728 discloses an ocular insert for use behind an eyelid, comprising a substantially circular disc having a concave posterior surface and a convex anterior surface.

[0013] U.S. Patent No. US6217896 disclosing a conjunctival insert for topical delivery of medication or lubrication into the conjunctival spaces and upon the ocular surface of human eye.

[0014] U.S. Patent No. US8679078 disclosing an ocular device for insertion into an eye and includes a body having an anterior surface and a posterior surface for placement on one of superior sclera and inferior sclera of the eye.

[0015] U.S Patent No. US3416530 disclosing a medication dispensing tablet for a human eye ball, the tablet comprising a cross-sectionally concavo-convex body of flexible material for insertion into the cul-de-sac of the conjunctiva.

[0016] U.S. Patent No. US3828777 disclosing an ocular device for the controlled and continuous administration of drug to the eye comprising a body of microporous drug release rate controlling material which is insoluble in tear fluid.

[0017] U.S. Patent No. US4014335 disclosing an ocular drug dispensing device for administering a drug at a controlled and continuous dosage unit rate to the eye to produce a local or systemic physiological or pharmacological effect.

[0018] U.S. Patent No. US5773021 disclosing a bioadhesive ophthalmic insert, which is intended for the prolonged and controlled release of a medicinal substance. The insert comprises a composite polymeric material matrix in which the medicinal substance is incorporated.

[0019] U.S. Patent No. US 10010502 disclosing a non-degradable topical ocular drug delivery device includes about 0.001% to about 10% w / w of at least one myopia-suppressing agent complexed with an immobile acid within a crosslinked polymer matrix.

[0020] International Patent Application No. WO2022 / 016268 disclosing biocompatible polyvinyl alcohol (PVA) matrices, composed of blends of differently hydrolyzed PVAs.

[0021] U.S. Patent Application Publication No. US20220168142A1 disclosing implantable bioerodible inserts for delivering an active pharmaceutical ingredient to the eye.

[0022] U.S. Patent Application Publication No. US20170226298A1 disclosing water-soluble films including a polyvinyl alcohol (PVOH) resin blend and optionally one or more additional components such as plasticizers, fillers, surfactants, and other additives. SUMMARY OF THE INVENTION

[0023] Following is a non-exclusive list including some examples of embodiments of the invention. The invention also includes embodiments which include fewer than all the features in an example and embodiments using features from multiple examples, also if not expressly listed below.

[0024] Example 1. An ophthalmic device having an elastomeric matrix, said elastomeric matrix comprising: a. poly(vinyl alcohol) (PVOH); b. one or more organic plasticizers; where a combined mass ratio of said one or more organic plasticizers to said PVOH is at least 2:1; and c. water; wherein said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length.

[0025] Example 2. The ophthalmic device according to example 1, wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

[0026] Example 3. The ophthalmic device according to example 1 or example 2, wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0027] Example 4. The ophthalmic device according to any one of examples 1-3, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0028] Example 5. The ophthalmic device according to any one of examples 1-4, wherein said PVOH comprises PVOH of two or more types that differ from one another in hydrolysis degree (HD).

[0029] Example 6. The ophthalmic device according to any one of examples 1-5, wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

[0030] Example 7. The ophthalmic device according to any one of examples 1-6, wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %. Example 8. The ophthalmic device according to any one of examples 1-7, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0031] Example 9. The ophthalmic device according to any one of examples 1-8, wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0032] Example 10. The ophthalmic device according to any one of examples 1-9, wherein a first type of said two or more types has chains with more than 2500 units.

[0033] Example 11. The ophthalmic device according to any one of examples 1-10, wherein a second type of said two or more types has chains with less than 1500 units.

[0034] Example 12. The ophthalmic device according to any one of examples 1-11, wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3.

[0035] Example 13. The ophthalmic device according to any one of examples 1-12, wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0036] Example 14. The ophthalmic device according to any one of examples 1-13, wherein said second type of PVOH makes more than 50% of said PVOH.

[0037] Example 15. The ophthalmic device according to any one of examples 1-14, wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0038] Example 16. The ophthalmic device according to any one of examples 1-15, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

[0039] Example 17. The ophthalmic device according to any one of examples 1-16, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0040] Example 18. The ophthalmic device according to any one of examples 1-17, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0041] Example 19. The ophthalmic device according to any one of examples 1-18, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

[0042] Example 20. The ophthalmic device according to any one of examples 1-19, wherein said water constitute less than 50 %wt of the total mass content of the matrix. Example 21. The ophthalmic device according to any one of examples 1-20, essentially devoid of covalent crosslinking.

[0043] Example 22. The ophthalmic device according to any one of examples 1-21, further comprising an active pharmaceutically agent.

[0044] Example 23. The ophthalmic device according to any one of examples 1-22, wherein the elastomeric matrix comprises the active pharmaceutically agent.

[0045] Example 24. The ophthalmic device according to any one of examples 1-23, wherein said ophthalmic device consists of ophthalmic acceptable ingredients.

[0046] Example 25. The ophthalmic device according to any one of examples 1-24, wherein at least 90% of said plasticizers (w / w) are ophthalmic demulcents.

[0047] Example 26. The ophthalmic device according to any one of examples 1-25, wherein said device weights between 1 mg and 50 mg or between Img and 30 mg.

[0048] Example 27. The ophthalmic device according to any one of examples 1-28, wherein said ophthalmic device is configured to be positioned on a surface of an eye.

[0049] Example 28. The ophthalmic device according to any one of examples 1-27, wherein said surface of the eye is outside a cornea of the eye, and at least partially underneath only one of the upper eyelid or the lower eyelid.

[0050] Example 29. The ophthalmic device according to any one of examples 1-28, wherein said device is configured for wearing away from the fornix.

[0051] Example 30. The ophthalmic device according to any one of examples 1-29, configured to deliver at least one pharmaceutically active agent to a surface an eye for between 5 minutes and 24 hours.

[0052] Example 31. The ophthalmic device according to any one of examples 1-30, configured to reside between an eyeball and an eyelid, and to move with the eyelid when the eyelid moves in respect to the eyeball.

[0053] Example 32. The ophthalmic device of any one of examples 1-31, configured to reside between an eyeball and an eyelid, and to stay with the eyelid when the eyeball moves in respect to the eyelid.

[0054] Example 33. The ophthalmic device according to any one of examples 1-32, having: a. a posterior surface, which in use is adjacent to an eye surface; and b. an anterior surface, which defines heights above said posterior surface; wherein two of said heights, distanced from each other by a distance of at most 1mm, differ from one another by a height difference of at least 1mm.

[0055] Example 34. The ophthalmic device according to any one of examples 1-32, having: a. a posterior surface; and b. an anterior surface that when the ophthalmic device is disposed in a relaxed configuration on a planar surface with the posterior surface adjacent to the planar surface defines heights above the planar surface, wherein two of said heights, distanced from each other by a distance of at most 1mm, differ from one another by a height difference of at least 1mm.

[0056] Example 35. An ophthalmic device according to any of examples 1 to 32, having: a. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; b. an anterior surface defining heights above said posterior surface; wherein each of two points on said anterior surface, distanced from one another along said anterior surface by at least 1 mm, has a respective slope of at least 45° with respect to said eye surface.

[0057] Example 36. An ophthalmic device according to any of examples 1 to 32, having: a. a posterior surface; and b. an anterior surface that when the ophthalmic device is disposed in a relaxed configuration on a planar surface with the posterior surface adjacent to the planar surface defines heights above the planar surface, wherein two points on said anterior surface are distanced from one another along said anterior surface by at least 1 mm, and each has a respective slope of at least 45° with respect to said planar surface.

[0058] Example 37. An ophthalmic device, configured to reside between an eye surface and an eyelid, comprising: a. a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers, said body characterized by: i. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; ii. an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein said retention portion has an edge structured to cause the ophthalmic device to move with the eyelid when the eyelid moves in respect to the eyeball. Example 38. The ophthalmic device according to example 37, wherein said edge is structured with a slope of said anterior surface extending from said posterior surface, said slope is characterized by an angle larger than 45° between said posterior surface and said anterior surface.

[0059] Example 39. The ophthalmic device according to example 37 or example 38, configured to completely reside between the eye surface and the eyelid.

[0060] Example 40. The ophthalmic device according to example any one of example 37-39, wherein said slope of more than 45 degrees is for at least of a length of 1mm.

[0061] Example 41. The ophthalmic device according to any one of examples 37-40, wherein said angle of a slope of said anterior surface extending from said posterior surface is from 45 degrees to 90 degrees.

[0062] Example 42. The ophthalmic device according to any one of examples 37-41, wherein said retention portion comprises a maximal height of from 0.5mm to 5mm.

[0063] Example 43. The ophthalmic device according to any one of examples 37-42, wherein said ophthalmic device has a length from about 3mm to about 10mm.

[0064] Example 44. The ophthalmic device according to any one of examples 37-43, wherein said ophthalmic device has a width from about 3mm to about 10mm.

[0065] Example 45. The ophthalmic device according to any one of examples 37-44, wherein a relation between a width and a length of said ophthalmic device is from about 1:1 to about 1:3.

[0066] Example 46. The ophthalmic device according to any one of examples 37-45, wherein a combined mass ratio of said one or more organic plasticizers to said one or more types of PVOH is at least 2:1.

[0067] Example 47. The ophthalmic device according to any one of examples 37-46, wherein said body swells isotropically when exposed to wet conditions.

[0068] Example 48. The ophthalmic device according to any one of examples 37-47, wherein said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length.

[0069] Example 49. The ophthalmic device according to any one of examples 37-48, wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0070] Example 50. The ophthalmic device according to any one of examples 37-49, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0071] Example 51. The ophthalmic device according to any one of examples 37-50, wherein said PVOH comprises PVOH of two or more types that differ from one another in hydrolysis degree (HD).

[0072] Example 52. The ophthalmic device according to any one of examples 37-51, wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

[0073] Example 53. The ophthalmic device according to any one of examples 37-52, wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %.

[0074] Example 54. The ophthalmic device according to any one of examples 37-53, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0075] Example 55. The ophthalmic device according to any one of examples 37-54, wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0076] Example 56. The ophthalmic device according to any one of examples 37-55, wherein a first type of said two or more types has chains with more than 2500 units.

[0077] Example 57. The ophthalmic device according to any one of examples 37-56, wherein a second type of said two or more types has chains with less than 1500 units.

[0078] Example 58. The ophthalmic device according to any one of examples 37-57, wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3.

[0079] Example 59. The ophthalmic device according to any one of examples 37-58, wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0080] Example 60. The ophthalmic device according to any one of examples 37-59, wherein said second type of PVOH makes more than 50% of said PVOH.

[0081] Example 61. The ophthalmic device according to any one of examples 37-60, wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0082] Example 62. The ophthalmic device according to any one of examples 37-61, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF). Example 63. The ophthalmic device according to any one of examples 37-62, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0083] Example 64. The ophthalmic device according to any one of examples 37-63, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0084] Example 65. The ophthalmic device according to any one of examples 37-64, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

[0085] Example 66. The ophthalmic device according to any one of examples 37-65, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

[0086] Example 67. The ophthalmic device according to any one of examples 37-66, essentially devoid of covalent crosslinking.

[0087] Example 68. The ophthalmic device according to any one of examples 37-67, further comprising at least one ophthalmically acceptable pharmaceutically active ingredient.

[0088] Example 69. The ophthalmic device according to any one of examples 37-68, wherein said at least one ophthalmic acceptable pharmaceutically active ingredient is carried by said elastomeric matrix.

[0089] Example 70. The ophthalmic device according to any one of examples 37-69, wherein said at least one ophthalmic acceptable pharmaceutically active ingredient is dispersed within said elastomeric matrix.

[0090] Example 71. The ophthalmic device according to any one of examples 37-70, wherein said at least one ophthalmic acceptable pharmaceutically active ingredient is encapsulated and then carried by said elastomeric matrix.

[0091] Example 72. The ophthalmic device according to any one of examples 37-71, wherein said water makes between 5 wt% and 50 wt% of said elastomeric matrix.

[0092] Example 73. The ophthalmic device according to any one of examples 37-72, wherein said ophthalmic device is configured to gain no more than 50% weight when immersed in simulated tear fluid for 5 minutes.

[0093] Example 74. The ophthalmic device according to any one of examples 37-73, wherein said ophthalmic device is obtainable from a liquid solution comprising water, a pharmaceutically active ingredient, the PVOH, and the organic plasticizers, without freezing. Example 75. The ophthalmic device according to any one of examples 37-74, wherein said ophthalmic device is obtained from a liquid solution comprising water, a pharmaceutically active ingredient, the PVOH, and the water-soluble organic liquids, without freezing.

[0094] Example 76. The ophthalmic device according to any one of examples 37-75, wherein said ophthalmic device is characterized by having a Young modulus of between 0.05 MPa and lOMPa.

[0095] Example 77. The ophthalmic device according to any one of examples 37-76, wherein said ophthalmic device is stable under 25°C±2°C and relative humidity of 60%±5% for at least three months.

[0096] Example 78. The ophthalmic device according to any one of examples 37-77, comprising two or more types of PVOH that differ from each other in a degree of hydrolysis.

[0097] Example 79. The ophthalmic device according to any one of examples 37-78, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device degrades at least 50% of a weight of said ophthalmic device under wet conditions within 24 hours.

[0098] Example 80. The ophthalmic device according to any one of examples 37-79, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device remains intact under wet conditions during the first 10 minutes.

[0099] Example 81. The ophthalmic device according to any one of examples 37-80, wherein said ophthalmic device is visible to naked eye on a background of bulbar conjunctiva.

[0100] Example 82. The ophthalmic device according to any one of examples 37-81, wherein said retention portion is defined by heights between said posterior surface and said anterior surface; and wherein a first height of said heights measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height of said heights measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0101] Example 83. The ophthalmic device according to any one of examples 37-82, wherein said device is configured for wearing away from the fornix.

[0102] Example 84. An ophthalmic device, configured to reside between an eye surface and an eyelid, comprising a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers, said body characterized by: i. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; ii. an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein a combined mass ratio of said one or more organic plasticizers to said one or more types of PVOH is at least 2:1.

[0103] Example 85. An ophthalmic device, configured to reside between an eye surface and an eyelid, comprising a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers, said body characterized by: i. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; ii. an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein ratios between said one or more organic plasticizers to said one or more types of PVOH is such that upon staying still in simulated tear fluid for a period of 15 minutes at room temperature, the device swells by less than 50% (v / v).

[0104] Example 86. The ophthalmic device according to example 84 or example 85, wherein said retention portion is configured to cause the ophthalmic device to move with the eyelid when the eyelid moves in respect to the eyeball.

[0105] Example 87. The ophthalmic device according to any one of examples 84-86, wherein an angle of a slope of said anterior surface extending from said posterior surface is larger than 45 degrees.

[0106] Example 88. The ophthalmic device according to any one of examples 84-87, wherein said angle of a slope of said anterior surface extending from said posterior surface is from 45 degrees to 90 degrees.

[0107] Example 89. The ophthalmic device according to any one of examples 84-88, wherein said retention portion comprises a maximal height of from 0.5mm to 5mm.

[0108] Example 90. The ophthalmic device according to any one of examples 84-89, wherein said ophthalmic device comprises a length from about 3mm to about 10mm.

[0109] Example 91. The ophthalmic device according to any one of examples 84-90, wherein said ophthalmic device comprises a width from about 3mm to about 10mm.

[0110] Example 92. The ophthalmic device according to any one of examples 84-91, wherein a relation between a width and a length of said ophthalmic device is from about 1:1 to about 1:3. Example 93. The ophthalmic device according to any one of examples 84-92, wherein said body is characterized by having an elliptical form.

[0111] Example 94. The ophthalmic device according to any one of examples 84-93, wherein said body is characterized by having a round form.

[0112] Example 95. The ophthalmic device according to any one of examples 84-94, wherein said body is characterized by having a dome-like form.

[0113] Example 96. The ophthalmic device according to any one of examples 84-95, wherein said body is characterized by having a half-elliptical sphere form.

[0114] Example 97. The ophthalmic device according to any one of examples 84-96, wherein said body swells isotropically when exposed to wet conditions.

[0115] Example 98. The ophthalmic device according to any one of examples 84-97, wherein said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length.

[0116] Example 99. The ophthalmic device according to any one of examples 84-98, wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

[0117] Example 100. The ophthalmic device according to any one of examples 84-99, wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0118] Example 101. The ophthalmic device according to any one of examples 84-100, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0119] Example 102. The ophthalmic device according to any one of examples 84-101, wherein said PVOH comprises PVOH of two or more types that differ from one another in hydrolysis degree (HD).

[0120] Example 103. The ophthalmic device according to any one of examples 84-102, wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%. Example 104. The ophthalmic device according to any one of examples 84-103, wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %.

[0121] Example 105. The ophthalmic device according to any one of examples 84-104, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0122] Example 106. The ophthalmic device according to any one of examples 84-105, wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0123] Example 107. The ophthalmic device according to any one of examples 84-106, wherein a first type of said two or more types has chains with more than 2500 units.

[0124] Example 108. The ophthalmic device according to any one of examples 84-107, wherein a second type of said two or more types has chains with less than 1500 units.

[0125] Example 109. The ophthalmic device according to any one of examples 84-108, wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3.

[0126] Example 110. The ophthalmic device according to any one of examples 84-109, wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0127] Example 111. The ophthalmic device according to any one of examples 84-110, wherein said second type of PVOH makes more than 50% of said PVOH.

[0128] Example 112. The ophthalmic device according to any one of examples 84-111, wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0129] Example 113. The ophthalmic device according to any one of examples 84-112, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

[0130] Example 114. The ophthalmic device according to any one of examples 84-113, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0131] Example 115. The ophthalmic device according to any one of examples 84-114, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0132] Example 116. The ophthalmic device according to any one of examples 84-115, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature. Example 117. The ophthalmic device according to any one of examples 84-116, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

[0133] Example 118. The ophthalmic device according to any one of examples 84-117, essentially devoid of covalent crosslinking.

[0134] Example 119. The ophthalmic device according to any one of examples 84-118, further comprising at least one ophthalmic acceptable pharmaceutically active ingredient.

[0135] Example 120. The ophthalmic device according to any one of examples 84-119, wherein said at least one ophthalmic acceptable pharmaceutically active ingredient is carried by said elastomeric matrix.

[0136] Example 121. The ophthalmic device according to any one of examples 84-120, wherein said at least one ophthalmically acceptable pharmaceutically active ingredient is dispersed within said elastomeric matrix.

[0137] Example 122. The ophthalmic device according to any one of examples 84-121, wherein said at least one ophthalmically acceptable pharmaceutically active ingredient is encapsulated and then carried by said elastomeric matrix.

[0138] Example 123. The ophthalmic device according to any one of examples 84-122, wherein said water makes between 5 wt% and 50 wt% of said elastomeric matrix.

[0139] Example 124. The ophthalmic device according to any one of examples 84-123, wherein said ophthalmic device is configured to gain no more than 50% weight when exposed to wet conditions.

[0140] Example 125. The ophthalmic device according to any one of examples 84-124, wherein said ophthalmic device is obtainable from a liquid solution comprising water, the active ingredient, the PVOH, and the water-soluble organic liquids, without freezing.

[0141] Example 126. The ophthalmic device according to any one of examples 84-125, wherein said ophthalmic device is obtained from a liquid solution comprising water, the active ingredient, the PVOH, and the water-soluble organic liquids, without freezing.

[0142] Example 127. The ophthalmic device according to any one of examples 84-126, wherein said ophthalmic device is characterized by having a Young modulus of between 0.05 MPa and lOMPa.

[0143] Example 128. The ophthalmic device according to any one of examples 84-127, wherein said ophthalmic device is stable under dry conditions for at least three months.

[0144] Example 129. The ophthalmic device according to any one of examples 84-128, comprising two or more types of PVOH that differ from each other in a degree of hydrolysis. Example 130. The ophthalmic device according to any one of examples 84-129, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device disintegrates under wet conditions within 24 hours.

[0145] Example 131. The ophthalmic device according to any one of examples 84-130, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device remains intact under wet conditions during the first 10 minutes.

[0146] Example 132. The ophthalmic device according to any one of examples 84-131, wherein said ophthalmic device is visible to naked eye on a background of bulbar conjunctiva.

[0147] Example 133. The ophthalmic device according to any one of examples 84-132, wherein said ophthalmic device is elongated and symmetrical, so that all orientations of the device are equivalent as long as an elongated side of the device lies at a given direction.

[0148] Example 134. The ophthalmic device according to any one of examples 84-133, wherein said retention portion is defined by heights between said posterior surface and said anterior surface; and wherein a first height of said heights measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height of said heights measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0149] Example 135. The ophthalmic device according to any one of examples 84-134, wherein said device is configured for wearing away from the fornix.

[0150] Example 136. An ophthalmic device, comprising: a. a body comprising an elastomeric matrix; said elastomeric matrix comprising between 5 %wt and 50 %wt water, and at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); said body characterized by: i. a posterior surface, configured to conform to a surface of an eye under an eyelid; and ii. an anterior surface defining a height of said body above said eye surface; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein an angle of a slope of said anterior surface extending from said posterior surface is larger than 45 degrees; and b. an active pharmaceutical ingredient (API) for treating an eye condition, said API is carried by said elastomeric matrix, and released from the matrix under wet conditions. wherein said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length. Example 137. The ophthalmic device according to example 136, wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

[0151] Example 138. The ophthalmic device according to example 136 or example 137, wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0152] Example 139. The ophthalmic device according to any one of examples 136-138, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0153] Example 140. The ophthalmic device according to any one of examples 136-139, wherein said PVOH comprises PVOH of two or more types that differ from one another in hydrolysis degree (HD).

[0154] Example 141. The ophthalmic device according to any one of examples 136-140, wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

[0155] Example 142. The ophthalmic device according to any one of examples 136-141, wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %.

[0156] Example 143. The ophthalmic device according to any one of examples 136-142, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0157] Example 144. The ophthalmic device according to any one of examples 136-143, wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0158] Example 145. The ophthalmic device according to any one of examples 136-144, wherein a first type of said two or more types has chains with more than 2500 units.

[0159] Example 146. The ophthalmic device according to any one of examples 136-145, wherein a second type of said two or more types has chains with less than 1500 units.

[0160] Example 147. The ophthalmic device according to any one of examples 136-146, wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3.

[0161] Example 148. The ophthalmic device according to any one of examples 136-147, wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0162] Example 149. The ophthalmic device according to any one of examples 136-148, wherein said second type of PVOH makes more than 50% of said PVOH.

[0163] Example 150. The ophthalmic device according to any one of examples 136-149, wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0164] Example 151. The ophthalmic device according to any one of examples 136-150, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

[0165] Example 152. The ophthalmic device according to any one of examples 136-151, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0166] Example 153. The ophthalmic device according to any one of examples 136-152, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0167] Example 154. The ophthalmic device according to any one of examples 136-153, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

[0168] Example 155. The ophthalmic device according to any one of examples 136-154, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

[0169] Example 156. The ophthalmic device according to any one of examples 136-155, essentially devoid of covalent crosslinking.

[0170] Example 157. The ophthalmic device according to any one of examples 136-156, wherein each of said plurality of ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, a polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0171] Example 158. The ophthalmic device according to any one of examples 136-157, wherein said ophthalmic lubricants comprise polyethylene glycol (PEG), and the mass content of the PEG in the elastomeric matrix is about equal that of the PVOH.

[0172] Example 159. The ophthalmic device according to any one of examples 136-158, wherein at least 35% of said ophthalmic acceptable lubricants consist of glycerol and propylene glycol. Example 160. The ophthalmic device according to any one of examples 136-159, wherein said elastomeric matrix is impregnated with said API.

[0173] Example 161. The ophthalmic device according to any one of examples 136-160, obtainable by mixing the API with water and ophthalmic demulcents to obtain a mother solution; and drying the mother solution at room temperature.

[0174] Example 162. The ophthalmic device according to any one of examples 136-161, obtainable without heating the mother solution.

[0175] Example 163. The ophthalmic device according to any one of examples 136-162, obtainable without heating the API.

[0176] Example 164. The ophthalmic device according to any one of examples 136-163, wherein said ophthalmic device is characterized, when under dry conditions, by at least one of the following mechanical properties: a. tensile strength of between 0.01 MPa and 10 MPa; b. Young modulus of between 0.05 MPa and 10 MPa; and c. elongation at break of between 50% and 1000%.

[0177] Example 165. The ophthalmic device according to any one of examples 136-164, wherein said ophthalmic device is configured to degrade in the eye and to lose at least 50% of its weight within 2 hours in an eye.

[0178] Example 166. The ophthalmic device according to any one of examples 136-165, wherein said retention portion is configured to keep said ophthalmic device in place when the device is worn, and the eye is rolled.

[0179] Example 167. The ophthalmic device according to any one of examples 136-166, wherein a first height perpendicular to a reference surface and measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height perpendicular to the reference surface and measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0180] Example 168. The ophthalmic device according to any one of examples 136-167, sized and shaped to be fully covered by the eyelid when worn under a lower eyelid.

[0181] Example 169. The ophthalmic device according to any one of examples 136-168, wherein said ophthalmic device is configured for self-administration.

[0182] Example 170. The ophthalmic device according to any one of examples 136-169, comprising an active ingredient for treating presbyopia. Example 171. The ophthalmic device according to any one of examples 136-170, for use in the treating of presbyopia.

[0183] Example 172. The ophthalmic device according to any one of examples 136-171, wherein said body is configured to minimize disturbance to the eyelid when the posterior surface resides on said surface of said eye under said eyelid

[0184] Example 173. The ophthalmic device according to any one of examples 136-172, wherein said device is configured for wearing away from the fornix.

[0185] Example 174. An ophthalmic drug product for use in the treatment of presbyopia, comprising: a. an elastomeric matrix comprising i. at most 45 %wt water, and ii. at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); and b. a pharmacological agent for treating presbyopia.

[0186] Example 175. The ophthalmic drug product according to example 174, wherein said ophthalmic drug product is an ophthalmic device according to any one of examples 1 to 173.

[0187] Example 176. An ophthalmic drug product consisting essentially of one or more pharmaceutically active ingredients (APIs), ophthalmic demulcents, and water, wherein the water is no more than 50% wt of the drug product.

[0188] Example 177. The ophthalmic drug product according to example 176, wherein 95% wt of said ophthalmic drug product consists only of API, ophthalmic demulcents, and water.

[0189] Example 178. The ophthalmic drug product according to example 176 or example 177, wherein said ophthalmic drug product is characterized by at least one of the following mechanical properties: tensile strength between 0.01 MPa and 10 MPa; elastic module between 0.05 MPa and 10 MPa; and elongation at break between 50% and 1000%.

[0190] Example 179. The ophthalmic drug product according to any one of examples 176-178, wherein no less than 3% wt and no more than 33% wt of said ophthalmic demulcents consist of PVOH.

[0191] Example 180. The ophthalmic drug product according to any one of examples 176-179, wherein said PVOH comprises two types of PVOH, which differ from one another in their degree of hydrolysis. Example 181. The ophthalmic drug product according to any one of examples 176-180, wherein said two types of PVOH, differ from one another in their chain length.

[0192] Example 182. The ophthalmic drug product according to any one of examples 176-181, comprising PVOH having a degree of hydrolysis of 97% or larger and PVOH having a degree of hydrolysis of 93% or lower.

[0193] Example 183. The ophthalmic drug product according to any one of examples 176-182, wherein a majority of said PVOH has a degree of hydrolysis of 93% or lower.

[0194] Example 184. The ophthalmic drug product according to any one of examples 176-183, wherein at least two thirds of said PVOH have a degree of hydrolysis of 93% or lower.

[0195] Example 185. The ophthalmic drug product according to any one of examples 176-184, wherein at least one of said one or more APIs is for treating presbyopia.

[0196] Example 186. The ophthalmic drug product according to any one of examples 176-185, wherein at least one of said one or more APIs is pilocarpine, phentolamine mesylate, oxymetazoline, carbachol, phospholine Iodine, brimonidine, aceclidine, and lipoic acid choline ester.

[0197] Example 187. The ophthalmic drug product according to any one of examples 176-186, wherein said ophthalmic drug product is configured to reside between a bulbar conjunctiva and an eyelid covering an eyeball, the device having a retention portion, sized and shaped so that when between the bulbar conjunctiva and the eyelid, the retention portion is pressed against the eyelid at a force hard enough so that movement of the eyelid in respect to the eyeball forces the ophthalmic device to move with the eyelid across the eyeball.

[0198] Example 188. The ophthalmic drug product according to any one of examples 176-186, wherein said ophthalmic drug product comprises: a posterior surface configured to be adjacent to an eye surface when said ophthalmic drug product is in the eye; an anterior surface defining heights above said eye surface; and a retention portion defined between a portion of said posterior surface and a corresponding portion of said anterior surface, wherein two of said heights, defined by said corresponding portion of the anterior surface and distanced from each other by at most 1mm, differ from one another by a height difference of at least 1mm.

[0199] Example 189. The ophthalmic drug product according to any one of examples 176-188, wherein said ophthalmic drug product comprises: a posterior surface configured to be adjacent to an eye surface when said ophthalmic drug product is in the eye; an anterior surface defining heights above said eye surface; and a retention portion defined between a portion of said posterior surface and a corresponding portion of said anterior surface, wherein two points on said portion of said anterior surface are distanced from one another along the anterior surface by at least 1 mm, and each having a respective slope of at least 45° with respect to said eye surface.

[0200] Example 190. The ophthalmic drug product according to any one of examples 176-189, wherein said ophthalmic drug product is an ophthalmic device according to at least one of examples 1, 37, 84, 85 and 136.

[0201] Example 191. A method of treating presbyopia, comprising continuously eluting a presbyopia treating drug for at least 5 minutes from a drug product according to any one of examples 174 to 189 to a surface of an eye diagnosed with presbyopia.

[0202] Example 192. An ophthalmic device according to any one of examples 1 to 173, configured to elute on an eye surface ophthalmic demulcents, said ophthalmic demulcents having a mass content that is at least half the mass content of the ophthalmic device.

[0203] Example 193. An ophthalmic device having a mass content, and being configured to elute on an eye surface ophthalmic demulcents having a mass content that is at least half the mass content of the ophthalmic device.

[0204] Example 194. A method of treating dry eye disease, comprising administering to a patient in need of said treatment an ophthalmic device according to example 192 or 193.

[0205] Example 195. An ophthalmic device, comprising: a. a body comprising an elastomeric matrix; said elastomeric matrix comprising between 5 %wt and 45 %wt water, and at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); said body characterized by: i. a posterior surface, configured to conform to a surface of an eye under an eyelid; ii. an anterior surface defining a height of said body above said eye surface; and iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein an angle of a slope of said anterior surface extending from said posterior surface is larger than 45 degrees; b. an active pharmaceutical ingredients (API) for treating an eye condition, said API is carried by said elastomeric matrix, and released from the matrix under wet conditions.

[0206] Example 196. The ophthalmic device according to example 195, wherein said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length. Example 197. The ophthalmic device according to example 195 or example 196, wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

[0207] Example 198. The ophthalmic device according to any one of examples 195-197, wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0208] Example 199. The ophthalmic device according to any one of examples 195-198, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0209] Example 200. The ophthalmic device according to any one of examples 195-199, wherein said PVOH comprises PVOH of two or more types that differ from one another in hydrolysis degree (HD).

[0210] Example 201. The ophthalmic device according to any one of examples 195-200, wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

[0211] Example 202. The ophthalmic device according to any one of examples 195-201, wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %.

[0212] Example 203. The ophthalmic device according to any one of examples 195-202, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0213] Example 204. The ophthalmic device according to any one of examples 195-203, wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0214] Example 205. The ophthalmic device according to any one of examples 195-204, wherein a first type of said two or more types has chains with more than 2500 units.

[0215] Example 206. The ophthalmic device according to any one of examples 195-205, wherein a second type of said two or more types has chains with less than 1500 units.

[0216] Example 207. The ophthalmic device according to any one of examples 195-206, wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3. Example 208. The ophthalmic device according to any one of examples 195-207, wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0217] Example 209. The ophthalmic device according to any one of examples 195-208, wherein said second type of PVOH makes more than 50% of said PVOH.

[0218] Example 210. The ophthalmic device according to any one of examples 195-209, wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0219] Example 211. The ophthalmic device according to any one of examples 195-210, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

[0220] Example 212. The ophthalmic device according to any one of examples 195-211, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0221] Example 213. The ophthalmic device according to any one of examples 195-212, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0222] Example 214. The ophthalmic device according to any one of examples 195-213, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

[0223] Example 215. The ophthalmic device according to any one of examples 195-214, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

[0224] Example 216. The ophthalmic device according to any one of examples 195-215, essentially devoid of covalent crosslinking.

[0225] Example 217. The ophthalmic device according to any one of examples 195-216, wherein each of said plurality of ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, a polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0226] Example 218. The ophthalmic device according to any one of examples 195-217, wherein said ophthalmic acceptable lubricants or demulcents comprise polyethylene glycol (PEG), and the mass content of the PEG in the elastomeric matrix is about equal that of the PVOH. Example 219. The ophthalmic device according to any one of examples 195-218, wherein at least 35% of said ophthalmic acceptable lubricants or demulcents consist of glycerol and propylene glycol.

[0227] Example 220. The ophthalmic device according to any one of examples 195-219, wherein said elastomeric matrix is impregnated with an ophthalmically acceptable active pharmaceutical ingredient.

[0228] Example 221. The ophthalmic device according to any one of examples 195-220, obtainable by mixing the API with water and ophthalmic demulcents to obtain a mother solution; and drying the mother solution at room temperature.

[0229] Example 222. The ophthalmic device according to any one of examples 195-221, obtainable without heating the mother solution.

[0230] Example 223. The ophthalmic device according to any one of examples 195-222, wherein said ophthalmic device is characterized by at least one of the following mechanical properties: a. tensile strength of between 0.01 MPa and 10 MPa; b. Young modulus of between 0.05 MPa and 10 MPa; and c. elongation at break of between 50% and 1000%.

[0231] Example 224. The ophthalmic device according to any one of examples 195-223, wherein said ophthalmic device is configured to degrade in the eye and to lose at least 50% of its weight within 2 hours in the eye.

[0232] Example 225. The ophthalmic device according to any one of examples 195-224, wherein said retention portion is configured to keep said ophthalmic device in place when the device is worn, and the eye is rolled.

[0233] Example 226. The ophthalmic device according to any one of examples 195-225, wherein a first height perpendicular to a reference surface and measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height perpendicular to the reference surface and measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0234] Example 227. The ophthalmic device according to any one of examples 195-226, sized and shaped to be fully covered by the eyelid when worn under a lower eyelid.

[0235] Example 228. The ophthalmic device according to any one of examples 195-227, wherein said ophthalmic device is configured for self-administration.

[0236] Example 229. The ophthalmic device according to any one of examples 195-228, wherein said device is configured for wearing away from the fornix. Example 230. An ophthalmic drug product for treating presbyopia, comprising: a. an elastomeric matrix comprising i. between 5 %wt and 45 %wt water, and ii. at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); and b. an active pharmaceutical ingredient (API) usable in treating presbyopia.

[0237] Example 231. The ophthalmic drug product according to example 230, wherein said ophthalmic drug product is an ophthalmic device according to any one of examples 1 to 229.

[0238] Example 232. A method of treating presbyopia, comprising continuously eluting an active pharmacological ingredient usable in treating presbyopia for at least 5 minutes from a drug product according to any one of examples 174 to 189 to a conjunctiva of an eye diagnosed with presbyopia.

[0239] Example 233. A method of treating an eye inflicted with dry eye syndrome, the method comprising topically administering to the eye an ophthalmic device comprising an elastomeric matrix having a mass content that elutes on a surface of the eye ophthalmic demulcents, said eluted ophthalmic demulcents making 50% or more of the mass content of the matrix.

[0240] Example 234. A method of treating an eye inflicted with dry eye syndrome, the method comprising topically administering to the eye an ophthalmic device according to any one of examples 36 to 64, and 160 to 204

[0241] Example 235. The method according to example 234, wherein the ophthalmic device comprises no API other than polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0242] Example 236. The method according to example 234 or example 235, wherein the ophthalmic device is according to the ophthalmic device according to anyone of the preceding claims.

[0243] Example 237. An ophthalmic drug product for use in the treatment of presbyopia, comprising: a. an elastomeric matrix comprising i. between 5 %wt and 45 %wt water, and ii. at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); and b. an active pharmaceutical ingredient (API) usable in treating presbyopia. Example 238. The ophthalmic drug product according to example 237, wherein said ophthalmic drug product is an ophthalmic device according to any one of the preceding claims.

[0244] Example 239. A method of treating dry eye disease, the method comprising administering to a patient in need of such treatment an ophthalmic device according to any one of the preceding claims.

[0245] Example 240. The method according to example 238, wherein the ophthalmic device comprises no API other than one or more of polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0246] Example 241. An ophthalmic drug product for use in the treatment of presbyopia, comprising: a. an elastomeric matrix comprising i. between 5 %wt and 45 %wt water, and ii. at least 50 %wt ophthalmic lubricants, of which between 5 %wt and 33 %wt is polyvinyl alcohol (PVOH); and b. an active pharmaceutical ingredient (API) usable in treating presbyopia.

[0247] Example 242. The ophthalmic drug product according to example 241, wherein said ophthalmic drug product is an ophthalmic device according to any one of the preceding claims.

[0248] Example 243. A method of treating dry eye disease, the method comprising administering to a patient in need of such treatment an ophthalmic device according to any one of the preceding claims.

[0249] Example 244. The method according to example 243, wherein the ophthalmic device comprises no API other than one or more of polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0250] Example 245. An ophthalmic device, configured to reside between an eye surface of an eyeball and an eyelid, comprising: a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers, said body characterized by: i. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; ii. an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein a combined mass ratio of said one or more organic plasticizers to said one or more types of PVOH is at least 2:1.

[0251] Example 246. The ophthalmic device according to example 245, wherein said retention portion is configured to cause the ophthalmic device to move with the eyelid when the eyelid moves in respect to the eyeball.

[0252] Example 247. The ophthalmic device according to example 245 or example 246, wherein an angle of a slope of said anterior surface extending from said posterior surface is larger than 45 degrees.

[0253] Example 248. The ophthalmic device according to any one of examples 245-247, wherein a relation between a width and a length of said ophthalmic device is from about 1:1 to about 1:3.

[0254] Example 249. The ophthalmic device according to any one of examples 245-248, wherein said body swells isotropically when immersed in simulated tear fluid for 15 minutes or less.

[0255] Example 250. The ophthalmic device according to any one of examples 245-249, further comprising at least one ophthalmic acceptable active pharmaceutical ingredients (API).

[0256] Example 251. The ophthalmic device according to any one of examples 245-250, wherein said water makes between 5 wt% and 50 wt% of said elastomeric matrix.

[0257] Example 252. The ophthalmic device according to any one of examples 245-251, wherein said ophthalmic device is configured to gain no more than 50% weight when immersed in simulated tear fluid for 15 minutes or less.

[0258] Example 253. The ophthalmic device according to any one of examples 245-252, wherein said ophthalmic device is obtainable from a liquid solution comprising water, the ophthalmically acceptable active pharmaceutical ingredient (API), the PVOH, and the water-soluble organic liquids, without freezing.

[0259] Example 254. The ophthalmic device according to any one of examples 245-253, comprising two or more types of PVOH.

[0260] Example 255. The ophthalmic device according to any one of examples 245-254, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device disintegrates under simulated tear fluid (STF) within 24 hours. Example 256. The ophthalmic device according to any one of examples 245-255, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device remains intact in simulated tear fluid (STF) during the first 10 minutes.

[0261] Example 257. The ophthalmic device according to any one of examples 245-256, wherein said ophthalmic device is visible to naked eye on a background of bulbar conjunctiva.

[0262] Example 258. The ophthalmic device according to any one of examples 245-257, wherein said ophthalmic device is elongated and symmetrical, so that all orientations of the device are equivalent as long as an elongated side of the device lies at a given direction.

[0263] Example 259. The ophthalmic device according to any one of examples 245-258, wherein said retention portion is defined by heights between said posterior surface and said anterior surface; and wherein a first height of said heights measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height of said heights measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0264] Example 260. The ophthalmic device, according to any one of examples 245-259, wherein said body includes a plurality of ophthalmic lubricants.

[0265] Example 261. The ophthalmic device, according to any one of examples 245-260, wherein each of said plurality of ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, a polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

[0266] Example 262. The ophthalmic device according to any one of examples 245-261, wherein said PVOH comprises PVOH of two or more types that differ from each other by chain length, degree of hydrolysis, or both.

[0267] Example 263. The ophthalmic device according to any one of examples 245-262, wherein at least 35 %wt of said two or more types of PVOH has a degree of hydrolysis lower than 90%.

[0268] Example 264. The ophthalmic device according to any one of examples 245-263, wherein said ophthalmic lubricants comprise polyethylene glycol (PEG), and the mass content of the PEG in the elastomeric matrix is about equal that of the PVOH.

[0269] Example 265. The ophthalmic device according to any one of examples 245-264, wherein at least 35% of said ophthalmic lubricants consist of glycerol and propylene glycol. Example 266. The ophthalmic device according to any one of examples 245-265, wherein said elastomeric matrix is impregnated with an ophthalmically acceptable active pharmaceutical ingredient.

[0270] Example 267. The ophthalmic device according to any one of examples 245-266, obtainable by mixing the API with water and ophthalmic demulcents to obtain a mother solution; and drying the mother solution at room temperature.

[0271] Example 268. The ophthalmic device according to any one of examples 245-267, obtainable without heating the mother solution.

[0272] Example 269. The ophthalmic device according to any one of examples 245-268, obtainable without heating the API.

[0273] Example 270. The ophthalmic device according to any one of examples 245-269, wherein said ophthalmic device is characterized by at least one of the following mechanical properties: a. tensile strength of between 0.05 MPa and 10 MPa; b. Young modulus of between 0.05 MPa and 10 MPa; and c. elongation at break of between 50% and 1000%.

[0274] Example 271. The ophthalmic device according to any one of examples 245-270, wherein said ophthalmic device is configured to lose at least 50% of its weight within 2 hours in an eye.

[0275] Example 272. The ophthalmic device according to any one of examples 245-271, wherein said retention portion is configured to keep said ophthalmic device in place when the device is worn, and the eye is rolled.

[0276] Example 273. The ophthalmic device according to any one of examples 245-272, wherein a first height perpendicular to a reference surface and measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height perpendicular to the reference surface and measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

[0277] Example 274. The ophthalmic device according to any one of examples 245-273, sized and shaped to be fully covered by the lower eyelid when worn under a lower eyelid.

[0278] Example 275. The ophthalmic device according to any one of examples 245-274, wherein said ophthalmic device is configured for self-administration.

[0279] Example 276. The ophthalmic device according to any one of examples 245-275, wherein said device is configured for wearing away from a fornix’ eye. Example 277. The ophthalmic device according to any one of examples 245-276, comprising two or more types of PVOH and wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

[0280] Example 278. The ophthalmic device according to any one of examples 245-277, comprising two or more types of PVOH and wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

[0281] Example 279. The ophthalmic device according to any one of examples 245-278, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

[0282] Example 280. The ophthalmic device according to any one of examples 245-279, comprising two or more types of PVOH and wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

[0283] Example 281. The ophthalmic device according to any one of examples 245-280, comprising two or more types of PVOH and wherein a first type of said two or more types has a hydrolysis degree from 97 % to 100 %.

[0284] Example 282. The ophthalmic device according to any one of examples 245-281, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

[0285] Example 283. The ophthalmic device according to any one of examples 245-282, comprising two or more types of PVOH and wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

[0286] Example 284. The ophthalmic device according to any one of examples 245-283, comprising two or more types of PVOH and wherein a first type of said two or more types has chains with more than 2500 units.

[0287] Example 285. The ophthalmic device according to any one of examples 245-284, comprising two or more types of PVOH and wherein a second type of said two or more types has chains with less than 1500 units.

[0288] Example 286. The ophthalmic device according to any one of examples 245-285, comprising two or more types of PVOH and wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3. Example 287. The ophthalmic device according to any one of examples 245-286, comprising two or more types of PVOH and wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

[0289] Example 288. The ophthalmic device according to any one of examples 245-287, comprising two or more types of PVOH and wherein said second type of PVOH makes more than 50% of said PVOH.

[0290] Example 289. The ophthalmic device according to any one of examples 245-288, comprising two or more types of PVOH and wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

[0291] Example 290. The ophthalmic device according to any one of examples 245-289, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

[0292] Example 291. The ophthalmic device according to any one of examples 245-290, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

[0293] Example 292. The ophthalmic device according to any one of examples 245-291, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

[0294] Example 293. The ophthalmic device according to any one of examples 245-292, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

[0295] Example 294. The ophthalmic device according to any one of examples 245-293, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

[0296] Example 295. The ophthalmic device according to any one of examples 245-294, essentially devoid of covalent crosslinking.

[0297] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0298] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0299] In the drawings:

[0300] Figure 1 is a method of use of an ophthalmic device, according to some embodiments of the invention;

[0301] Figure 2 is a method of treatment using an ophthalmic device, according to some embodiment of the invention;

[0302] Figure 3A is a simplified schematic cross sectional view of an eye;

[0303] Figure 3B is a simplified schematic cross sectional view of an ophthalmic device in position on an eye surface, when the eye is closed, according to some embodiments of the invention;

[0304] Figure 3C is a simplified schematic cross sectional view of an ophthalmic device in position on an eye surface, when the eye is open, according to some embodiments of the invention;

[0305] Figure 3D is a simplified schematic top view of an ophthalmic device in position on an eye surface, according to some embodiments of the invention;

[0306] Figure 4A is a simplified schematic top view of an ophthalmic device in position on an eye surface, according to some embodiments of the invention;

[0307] Figure 4B is a simplified schematic cross sectional view of an ophthalmic device in position on an eye surface, when the eye is closed, according to some embodiments of the invention;

[0308] Figure 5 is a method of use of an ophthalmic device, according to some embodiments of the invention;

[0309] Figure 6A is a simplified schematic top view of an ophthalmic device 600 in position on an eye surface underneath an eyelid, according to some embodiments of the invention;

[0310] Figure 6B is a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention;

[0311] Figure 7 is a simplified schematic illustrating cross sections of portions of devices, according to some embodiments of the invention;

[0312] Figures 8, 9, 10, 11 and 12 are simplified schematic top views of devices, according to some embodiments of the invention;

[0313] Figure 13 A is a simplified schematic view of an ophthalmic device, according to some embodiments of the invention; Figure 13B is a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention;

[0314] Figure 13C is a simplified schematic top view of an ophthalmic device, according to some embodiments of the invention;

[0315] Figure 14 is a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention;

[0316] Figure 15A is a simplified schematic top view of an ophthalmic device, according to some embodiments of the invention;

[0317] Figure 15B is a simplified schematic view of an ophthalmic device, according to some embodiments of the invention;

[0318] Figure 15C is a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention;

[0319] Figure 15D is a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention;

[0320] Figures 16, 17, 18, 19 and 20 are simplified schematic top views of devices, according to some embodiments of the invention;

[0321] Figures 21, 22, 23 and 24 are simplified schematic cross sections of devices, according to some embodiments of the invention;

[0322] Figure 25A is a simplified schematic cross sectional view of a device positioned on an eye surface, according to some embodiments of the invention;

[0323] Figure 25B is a simplified schematic cross sectional view of a device, according to some embodiments of the invention;

[0324] Figure 26 is a simplified schematic cross sectional view of a device, according to some embodiments of the invention;

[0325] Figure 27 A is a simplified schematic top view of an ophthalmic device, according to some embodiments of the invention;

[0326] Figure 27B is a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention;

[0327] Figure 27C is a simplified schematic cross sectional view of a device 2700, according to some embodiments of the invention;

[0328] Figure 28 is a process of ophthalmic device degradation, according to some embodiments of the invention;

[0329] Figure 29 is a simplified schematic cross sectional view of a device, according to some embodiments of the invention; Figures 30A-B are simplified schematic cross sectional views of a device, according to some embodiments of the invention;

[0330] Figure 31A is a simplified schematic cross section view of an ophthalmic device on an eye surface, according to some embodiments of the invention;

[0331] Figure 3 IB is a simplified schematic view of an ophthalmic device, according to some embodiments of the invention;

[0332] Figure 31C is a simplified schematic to view of an ophthalmic device, according to some embodiments of the invention;

[0333] Figures 32, 33, 34, 35, 36 and 37 are simplified schematic cross section views of portions of ophthalmic devices, according to some embodiments of the invention;

[0334] Figures 38, 39, 40, 41, 42, 43 and 44 are simplified schematic cross sectional views of devices, according to some embodiments of the invention;

[0335] Figures 45, 46, 47, 48, 49 and 50 are simplified schematic cross sectional views of double layer devices according to some embodiments of the invention;

[0336] Figures 51, 52, 53, 54, 55, 56, 57 and 58 are simplified schematic cross sectional views of multi-layer devices, according to some embodiments of the invention;

[0337] Figure 59A is a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention;

[0338] Figure 59B is a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention;

[0339] Figure 60 is a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention;

[0340] Figure 61 is a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention;

[0341] Figure 62A is a simplified schematic cross sectional view of a portion of an eye surface, according to some embodiments of the invention;

[0342] Figure 62B is a simplified schematic cross section view of an ophthalmic device on an eye surface, according to some embodiments of the invention;

[0343] Figure 62C is a simplified schematic cross section view of an ophthalmic device on an eye surface, according to some embodiments of the invention;

[0344] Figures 63A-C are simplified schematic cross sectional views of a portion of a device on an eye surface, according to some embodiments of the invention;

[0345] Figures 64, 65 and 66 are simplified schematic cross sectional views of multi-layer devices, according to some embodiments of the invention; Figures 67A-F are simplified schematic cross sections of a portion of a device as residence time of the device progresses, according to some embodiments of the invention;

[0346] Figure 68 is a flowchart of a disintegration progression of a device, according to some embodiments of the invention;

[0347] Figures 69A-C are simplified schematic cross sections of a device as residence time of the device progresses, according to some embodiments of the invention;

[0348] Figures 70A-D are simplified schematic cross sections of a device as residence time of the device progresses, according to some embodiments of the invention;

[0349] Figure 71 is a simplified schematic cross section of a device, according to some embodiments of the invention;

[0350] Figure 72 is a simplified schematic cross section of a device, according to some embodiments of the invention;

[0351] Figures 73A-B are simplified schematic cross sectional views of a device on an eye surface 7304, according to some embodiments of the invention;

[0352] Figures 74A-D are simplified schematic cross sectional views of a film, according to some embodiments of the invention

[0353] Figure 75 is a method of manufacture, according to some embodiments of the invention;

[0354] Figures 76A-C are simplified schematic cross sectional views of a device, according to some embodiments of the invention;

[0355] Figure 77 is a graph illustrating exemplary degradation characteristics of three different elastomeric matrix compositions, as they evolve in time under wet conditions, according to some embodiments of the invention;

[0356] Figure 78 is a graph illustrating degradation of some matrices during wetting and drying cycle, according to some embodiments of the invention;

[0357] Figure 79 is a graph plotting clinical results obtained according to embodiments of the present invention in comparison with published data related to eye-drops; and

[0358] Figure 80 is a graph showing the effect of an ophthalmic device according to embodiments of the present invention on near visual acuity (NV A) of two patients.

[0359] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0360] The present invention, in some embodiments thereof, relates to shaped polyvinyl alcohol (PVOH) based elastomeric matrixes for ophthalmic uses and, more particularly, but not exclusively, to such matrixes that are biodegradable or bioerodible. The terms “biodegradable” and “bioerodible” (as well as their inflictions, such as biodegradability and bioerodibility) are used herein interchangeably. For example, a matrix may be considered biodegradable if it erodes mechanically in the body.

[0361] Overview

[0362] The present invention, in some embodiments thereof, provides an ophthalmic drug product, uses thereof, and methods of its manufacturing. The ophthalmic drug product is preferably an ophthalmic device. All the features of the drug products described herein may also be found in any ophthalmic device described herein, and vice versa. In some embodiments, the ophthalmic device is configured to remain between a bulbar conjunctiva (ocular conjunctiva) and an eyelid, more particularly, between the ocular conjunctiva covering the sclera and the palpebral conjunctiva (tarsal conjunctiva), covering the eyelid. The tarsal and ocular conjunctivae meet at the fornix conjunctiva, and, in some embodiments, the device is configured for wearing away from the fornix, closer to the opening of the eyelid. In some embodiments, the ophthalmic device extends under either the lower eyelid or the upper eyelid. A potential advantage of having a device positioned under either and not both is that it potentially provides a smaller and more comfortable device, which in some embodiments may be inserted, and optionally taken out, by the patient himself. In some embodiments, the ophthalmic device is configured to reside between an eyeball and an eyelid, and to move with the eyelid when the eyelid moves in respect to the eyeball. In some embodiments, the ophthalmic device is configured to reside between an eyeball and an eyelid, and to stay with the eyelid when the eyeball moves in respect to the eyelid. In some embodiments, the ophthalmic device is configured to reside between an eye surface and an eyelid, and it comprises a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers. In some embodiments, the body characterized by: a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; where the retention portion has an edge structured to cause the ophthalmic device to move with the eyelid when the eyelid moves in respect to the eyeball.

[0363] In some embodiments, the ophthalmic device is configured to remain between the ocular and tarsal conjunctivae even when the eyelid or eyeball moves one in respect to the other. In some embodiments, during movement between the eyelid and the eyeball, the device moves with the eyelid across the eyeball, and in other embodiments, the device moves with the eyeball.

[0364] The embodiments in which the device moves with the eyeball or with the eyelid differ from one another in the balance between a grabbing force and an attaching force. The grabbing force acts between the edge of the eyelid and the edge of the device adjacent to the eyelid; and the attaching force acts on the posterior surface of the device (facing the eye surface). The attaching force may include, for example, adhesive friction force (traction force), and / or suction force.

[0365] In some embodiments, the grabbing force is larger than the attaching force, and the ophthalmic device moves with the eyelid across the eyeball. In some embodiments, the attaching force is larger than the grabbing force, and the ophthalmic device moves (or stays) with the eyeball.

[0366] In some embodiments, the ophthalmic device is configured to have enlarged grabbing force by including a retention portion with a steep leading edge. In some embodiments, the leading edge is the edge adjacent to the opening of the eyelid. In some embodiments, the retention portion is a portion of the ophthalmic device, defined between a portion of the posterior surface and a corresponding portion of the anterior surface, which is the surface of the device facing the eyelid. In some embodiments, the anterior surface defines heights above the eye surface. In some embodiments, to have enlarged grabbing force, the retention portion is optionally structured with two of the heights, defined by the corresponding portion of the anterior surface, being both close to each other, and having between them a large height difference, so as to create an angle of 45 degrees or more between the anterior surface and the eye surface. For example, the two heights may be distanced from each other by at most 1mm, while differ from one another by a height difference of at least 1mm.

[0367] In some embodiments, the ophthalmic device is configured to have enlarged attaching force, for example, by including one or more cavities, configured to receive therein a portion of the ocular conjunctiva, so as to enlarge the friction between the device and the eyeball. Similarly, in some embodiments, the ophthalmic device is configured to have enlarged grabbing force, for example, by including one or more cavities, configured to receive therein a portion of the tarsal conjunctiva, so as to enlarge the friction between the device and the eyelid.

[0368] In some embodiments, an ophthalmic device may be configured to move with the eyelid across the eyeball by having a steep retention portion, with no cavities at the posterior surface.

[0369] In some embodiments, an ophthalmic device may be configured to move with the eyeball by having a retention portion which is not steep, and having cavities at the posterior surface.

[0370] In some embodiments, the ophthalmic device has both a posterior surface with one or more cavities and a steep retention portion, and the device behavior when the eyeball moves in respect of the eyelid is determined by the relative effects of the cavities and steepness of the retention portion.

[0371] In some embodiments with steep retention portion, the retention portion is pressed hard against the eyelid, optionally, at a force hard enough to overcome friction between the posterior surface and the eye surface. Such hard press between the eyelid and the retention portion may cause significant discomfort to the wearer of the device. In some embodiments, to prevent such discomfort, the retention portion is made of a material soft enough not to irritate the eye when pressed against the eyelid even at the hard force required to drag the device with the eyelid.

[0372] In some embodiments, the required softness may be achieved with an elastomeric matrix formulated with water, PVOH, and a large amount plasticizers. The amount of the plasticizers may be considered large if it is larger than, or, preferably, at least double (in mass) than the mass amount of the PVOH. In some such embodiments, the mass of the PVOH and the plasticizers together is 70% or more of the total mass of the matrix excluding the water. In some embodiments, said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length. In some embodiments, each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix. In some embodiments, the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: short chains and is partially hydrolyzed; long chains and is partially hydrolyzed; short chains and is fully hydrolyzed. In some embodiments, short chains are of 200 to 2000 monomeric units; long chains are of 2200 to 5000 monomeric units; fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and partially hydrolyzed is of hydrolysis degree of 95% or less.

[0373] In some embodiments, the required softness may be achieved with an elastomeric matrix, having at least one of the following mechanical characteristics:

[0374] Tensile strength of between 0.01 MPa and 10 MPa, optionally 0.05 MPa to 10 MPa. Optionally, the tensile strength is smaller than lOMPa, smaller than 4MPa, smaller than 3MPa or smaller than 2 MPa;

[0375] Elastic modulus of between 0.01 MPa and 2.5 MPa, optionally between 0.05 MPa and 10 MPa. Optionally, the elastic modulus is smaller than lOMPa, smaller than 4MPa, smaller than 3MPa or smaller than 2 MPa;

[0376] Elongation at breakage of between 50% and 1000%, or larger. See also Mechanical Properties shown in Example 8, below.

[0377] In some embodiments, after the ophthalmic device is in the eye for some time (e.g., 5 or 10 minutes, 30 minutes, 1 hour, or four hours, or intermediate durations), the properties of the elastomeric matrix change. In some embodiments, this process, generally referred to herein as “degradation”, may change the balance of forces between the device and the tarsal conjunctiva on the one hand, and the device and the ocular conjunctiva on the other hand. In some embodiments, the degradation improves the fit to the anatomical locale at which the device seats. For example, the device may loosen its attachment to the eye surface (ocular conjunctiva), e.g., due to change in shape, and strengthen its attachment to the eyelid surface (tarsal conjunctiva), e.g., due to development of mucoadhesive properties of the matrix or better fitting to the conjunctiva. Thus, in some embodiments, after staying for some time in the eye, the degradation of the device may have an effect of releasing the device from the eye surface, while adhering the device to the eyelid and preventing the device from arriving (e.g., by floating on tear fluid) to the cornea, from which it might be quickly expelled by natural expulsion mechanisms.

[0378] In some embodiments, the ophthalmic device is configured for residing in the eye, e.g., in contact with an outer surface of an eyeball and / or with an inner surface of an eyelid, for long periods, for example, of up to 24 hours without activating mechanisms that naturally expel foreign bodies from the eye, such as, eyeball movements, blinking, and increased tendency to rub the eye. In some embodiments, while such mechanisms may be activated for a short period immediately after administering the ophthalmic device, they are soon lessened to an extent that the eye is not irritated, and the ophthalmic device remains in the eye without expulsion.

[0379] In some embodiments, this fast calming of the eye is achieved, inter alia, by the matrix being soft and supple even before being inserted to the eye, and particularly in its dry form. In some embodiments, the suppleness of the matrix may be expressed in being readily adaptable to new environments, and capable of being bent and / or folded without creases, cracks, or breaks. In some embodiments, the softness, in combination with the pliability (or suppleness) allows the matrix to flex and adapt in shape to the space available in the anatomical space at which it is inserted, e.g., in the lid wiper space between the lower eyelid and bulbar conjunctiva. In some embodiments, flexing and shape adaptation improves the fit between the ophthalmic device and the space in the eye over time, thus potentially lessen discomfort and allowing long residence of the ophthalmic device on the eye.

[0380] In some embodiments, the ophthalmic device is configured to be stored for long periods under dry conditions without losing its shape, softness and / or elasticity, and thus enjoys particularly long shelf life.

[0381] In some embodiments, the ophthalmic device is configured to shrink and swell, when taken out from the dry conditions and into inserted into water (or wet conditions).

[0382] In some embodiments, shrinking and swelling is characterized by being substantially isotropical. As used herein, shrinking or swelling substantially isotropically means going through size change along each dimension by the same amount ± about 20%. For example, in ophthalmic devices having rectangular shape, the length, width, and thickness (as may be measured, e.g., by a caliber) change by the same amount ± about 20%. In ophthalmic devices having cylindrical shape, the diameter and the height change by the same amount ± about 20%. In some embodiments, the total swelling, in addition to being isotropic, is not larger than 50% by volume, that is, each dimension (e.g., length, width, and depth) may be enlarged by not more than about 15% in the first minute or two after being immersed in water. In some embodiments, after the first minute or two, the drug product does not continue to swell, but may get smaller, e.g., due to degradation. In some embodiments, the requirement for isotropic swelling of 50% or less means that the enlargement along each direction (e.g., as measured by a caliber) is of 18% (15±3)% or less. In some embodiments, the ophthalmic device, and / or the elastomeric matrix comprised in it, is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5, 10, or 15 minutes. In some embodiments, the ophthalmic device, or the elastomeric matrix, swells by less than 50 % by volume when immersed in simulated tear fluid for 5, 10, or 15 minutes at room temperature.

[0383] In some embodiments, the isotropic swelling and shrinking cause the ophthalmic device to have substantially the same shape (even if not the same volume) under dry and wet conditions (at least for the first minutes under wet conditions). As used herein, dry conditions are conditions in which the drug product is kept under ambient humidity, but with no direct contact with liquids, including water and aqueous liquids. Wet conditions are conditions in which the drug product is kept in contact with aqueous liquids, such as water, tear fluid, tear simulation fluid, or the like.

[0384] In some embodiments, the ability to stay in the eye with only limited and short irritation may also benefit from the shape of the ophthalmic device. For example, in some embodiments, the soft and pliable matrix is shaped to include a retention portion, adapted to hold the drug product in its place, e.g., in a space between the bulbar conjunctiva and the eyelid. In some embodiments, the retention portion is adapted to hold the drug product in a space between the bulbar conjunctiva and the eyelid when the device is worn, and the eye is rolled. In some embodiments, the retention portion may prevent the ophthalmic device from escaping to other portions of the eye, for example, to under the upper eyelid, where the ophthalmic device might cause more discomfort, despite its high level of softness and pliability. In some embodiments, the softness, pliability, and suppleness of drug product allows making it relatively large (e.g., having an area of between 15 mm2and 35 mm2parallel to the eye surface and up to 5 mm thickness) without disturbing the eye.

[0385] In some embodiments, mechanical properties associated with the softness and elasticity of the ophthalmic device usually include at least one of the following: (i) a tensile strength of between 0.01 MPa and 2 MPa, optionally between 0.05 MPa and 1 MPa; (ii) elastic modulus (also known as Young modulus under tension) of between 0.01 MPa and 2.5 MPa, optionally between 0.05 MPa and 2 MPa; (iii) elongation at break of from about 50% up to about 1000%, optionally from about 100% to about 900%, optionally between 200% and 600%; and (iv) compression module (also known as Young’s modulus under compression) of between 0.05 MPa and 2.5 MPa, optionally between 0.1 MPa and 2.0 MPa.

[0386] An aspect of some embodiments of the invention relates to elastomeric matrices (referred hereinafter just as “matrix” or “matrices / matrixes”), which comprise one or more types of PVOH in order to achieve a matrix having determined and / or desired mechanical properties. In some embodiments, the elastomeric matrices are PVOH-based, in the sense that PVOH is the sole or main film forming polymer in the matrix.

[0387] In some embodiments, a matrix is designed to dissolve and / or degrade under wet conditions according to predetermined timeline requirements. In some embodiments, the timeline of degradation is controlled by choosing a composition of the one more types of PVOH in the matrix. In some embodiments, the composition is optionally characterized by the various types of PVOH included in the composition and their relative masses, or the mass portion of the total PVOH provided by each of the types.

[0388] In some embodiments, when referring to “wet conditions”, it should be understood to relate to conditions wherein a matrix of the invention is in direct contact with liquid (immersed in the liquid or after immersion in the liquid and before the liquid evaporated or wiped away). In some embodiments, the liquid is a naturally occurring bodily fluid, including but not limited to blood, saliva, tears, excreta, body tissue, tissue fluids), an aqueous solution (e.g., of one or more organic plasticizers), a buffer solution, and any combinations thereof. In some embodiments, the liquid is naturally occurring or simulating a naturally occurring fluid, such as artificial tear fluid. In some embodiments, artificial tear fluid is based on an aqueous solution containing about 0.67 % sodium chloride, about 0.2 % sodium bicarbonate and about 0.008 % calcium chloride. In some embodiments, “wet conditions” refer to the conditions when the matrix is positioned on mucous tissue of a human, for example, on buccal tissue or an eye surface.

[0389] In some embodiments, the term degradation of a matrix is defined as the change in properties of the matrix over time under wet conditions, and “degradability” as the tendency to degrade or the rate of degradation.

[0390] In some embodiments, the change in properties may include, for example, a change or loss in mass of one or more of the matrix components or of the matrix as a whole. For example, while plasticizers that leave the ophthalmic device may be replaced by water, in some embodiments, PVOH itself leaves the ophthalmic device, and thus, the device loses weight. Alternatively, or additionally, the change may include change in mechanical properties, shape, and / or size of the matrix. Alternatively, or additionally, the degradation may be expressed as dissolution, breakage, tear, and / or crumbling of the matrix. In general, the degradation may be due to breakage of bonds between the different constituents of the matrix (e.g., PVOH, plasticizers, and water) while each of the constituents stays intact. In some embodiments, the degradation allows clearing the ophthalmic device, or the elastomeric matrix it comprises, from the eye, for example, by tears, that may wash the matrix constituents, crumbs, and / or remains out of the eye.

[0391] In some embodiments, the kind of degradation, e.g., the change from soft solid to slime, dissolution, mass loss, or change in tearability, may depend on the types of PVOH included in the matrix. For example, the inventors found that some matrices that include long chain fully hydrolyzed (LCFH) PVOH and short chain partially hydrolyzed (SCPH) PVOH tend to become “slimy” when immersed in simulated tear fluid (STF). In such embodiments, the increased sliminess may be accompanied by a decrease in compression modulus with time under STF. In some embodiments, some matrices that include LCFH PVOH and long chain partially hydrolyzed (LCPH) PVOH tend to become more easily dissolvable in STF, in the sense that they may dissolve to clear solution in cold water. In some embodiments, some matrices that include LCFH PVOH and short chain fully hydrolyzed (SCFH) PVOH tend to be torn more easily the longer they are immersed in STF. In some embodiments, increased susceptibility to tearing of such matrices may be accompanied by decrease in compression strength with time under STF.

[0392] See also Exemplary Mechanical Properties in Example 8 below.

[0393] In some embodiments, the degradation may obviate the need to take the matrix out of the body. For example, the products of the degradation may be expelled from the body naturally, e.g., by tear fluid (if the matrix is used in the eye) by urea (if the matrix is used in the bladder), etc. In case of ophthalmic devices, after some time in the eye, an ophthalmic device made of a degradable matrix may leave the eye naturally, with no need to take it out actively from the eye. For example, the device may fully dissolve and leave the eye with tear fluid, or disintegrate to such small parts that may be expelled from the eye as any other foreign object.

[0394] In some embodiments, slightly pressing a degradable matrix (e.g., used as ophthalmic device) may bring to immediate change in the form or integrity of the matrix, so an ophthalmic device may be naturally expelled shortly after being pressed.

[0395] In some embodiments, the degradation causes the matrix to acquire a shape and / or consistency that are comfortable to the anatomic locale at which it is used, so it may remain there. For example, an ophthalmic device may acquire a shape conforming to the space between the ocular and tarsal conjunctivae, where it may rest without discomforting the patient until it is degraded and expelled from the eye. In some embodiments, on the way out from the eye a degraded device might come across the cornea and cause temporary discomfort. In some embodiments, the terms “dissolve” and “degrade” are interchangeable and refer to the process by which the elastomeric matrices change, e.g., under wet conditions. The change may be, for example, from a solid state to a completely degraded state. The change may be, for example, loss in mass. In some embodiments, a completely degraded state can be defined, for example, as a degradation state of the matrix when the matrix cannot be seen by the naked eye, for example because the matrix has disintegrated to particles of very small size, and / or, for example, a state of the matrix when the matrix elastically changes shape and / or does not hold a defined form under certain external pressures, for example, in matrices used in or applied to any tissue, for example on the eye, pressure from the eyelid on the matrix. The terms “shape” and “geometry” are interchangeable and refer to the form of the matrix.

[0396] In some embodiments, the matrixes comprise a mixture of two or more types of PVOH. In some embodiments, the differences in the types of PVOH are in one or more of hydrolysis degree and length of PVOH chains. In some embodiments, the higher the quantity of highly hydrolyzed PVOH in the matrix, the longer the time that will take for the matrix to fully degrade. In some embodiments, said PVOH comprises PVOH of two or more types that differ from one another in one or both of hydrolysis degree (HD) and chain length. In some embodiments, each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix. In some embodiments, the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of: short chains and is partially hydrolyzed; long chains and is partially hydrolyzed; short chains and is fully hydrolyzed. In some embodiments, short chains are of 200 to 2000 monomeric units; long chains are of 2200 to 5000 monomeric units; fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and partially hydrolyzed is of hydrolysis degree of 95% or less.

[0397] In some embodiments, the number of PVOH types is three or more.

[0398] In some embodiments, two of the types of PVOH differ in chain length, e.g., by at least 1000 or 1500 units. In some such embodiments, the two of the types of PVOH have similar degrees of hydrolysis, e.g., between 97% and 100%.

[0399] In some embodiments, two of the types of PVOH differ in degree of hydrolysis, e.g., one has D.H of 97% or more, and the other of 93%, 90%, or less. In some such embodiments, the two types of PVOH differ also in chain length, e.g., by at least 1000 or 1500 units. For example, the PVOH type with the higher degree of hydrolysis may have longer chains. In another example, the PVOH type with the higher degree of hydrolysis may have shorter chains. In some embodiments, in which two of the types of PVOH differ in degree of hydrolysis, the two types of PVOH have similar lengths, differing from each other by, e.g., less than 500 units. In some embodiments, the PVOH with short chains has an average chain length of between about 200 and about 2000, monomeric units; and the PVOH with long chains has average chain length between about 2200 and about 5000 monomeric units. In some embodiments, the fully hydrolyzed PVOH has a hydrolysis degree of 97% or more; and the partially hydrolyzed PVOH has hydrolysis degree of 94% or less. In some embodiments, short chains have a molecular weight lower than about 50 Kg / Mol to about 80Kg / Mol, while long chains have a molecular weight higher than about 50 Kg / Mol to about 80Kg / Mol.

[0400] In some embodiments, the matrices are specifically designed to keep their geometry / shape under wet conditions, before the initiation of the degradation process. The degradation process may begin, in some embodiments, after 1 minute under wet conditions and in other embodiments after several hours under wet conditions, or within intermediate times. A matrix that keeps its geometry may be shaped outside the body (e.g., the eye), knowing that the same shape will be retained at least for some period after contacting the body.

[0401] In some embodiments, the elastomeric matrix comprises PVOH, one or more organic plasticizers, and optionally water. In some embodiments, the elastomeric matrix is characterized by a ratio between the combined mass of the one or more plasticizers to a combined mass of the PVOH of the various types that is at least 2:1.

[0402] . total mass of plasticizer (s) 2

[0403] That is, - > total mass of PVOH 1

[0404] This ratio is referred to herein as “combined mass ratio”.

[0405] In some embodiments, the elastomeric matrix comprises more than one type of plasticizer.

[0406] In some embodiments, the matrix is characterized by keeping a geometry when coming in contact with a wet environment, for example when put in contact with the eye or other body tissue. In some embodiments, in addition to keeping its geometry when coming in contact with a wet environment, optionally, the matrix increases its volume. In some embodiments, the volume increase is by no more than 50%. In some embodiments, the swelling is the same in all directions, so that the volume changes, but the geometry is kept. In some embodiments, the elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5, 10, or 15 minutes. In some embodiments, the elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5, 10, or 15 minutes at room temperature.

[0407] In some embodiments, the mechanical properties and / or the degradability of the elastomeric matrix depends on the types of PVOH used to form the matrix, and their respective masses. For example, when the PVOH includes mainly long chain fully hydrolyzed (hereinafter LCFH) PVOH and a minority of short chain partially hydrolyzed (hereinafter SCPH) PVOH the matrix degrades more slowly than when the LCFH PVOH is the minority of the PVOH in the matrix and SCPH PVOH is the majority thereof.

[0408] The following table (Table 1) provides examples of some commercially available types of PVOH. The list is taken from the brand Mowiol™, but similar materials are available from other sources. The PVOH type named “30k” in the table below (Table 1) is not of the Mowiol brand. All PVOH types used in the examples and measurements recited herein were carried out with PVOH sold under the brand of Emprove™ or with the 30k PVOH (which is Sigma Aldrich 8.21039).

[0409] TABLE 1

[0410] In some embodiments, the elastomeric matrix is used as an ophthalmic device or make part of an ophthalmic device. In some embodiments, the ophthalmic device may be configured to be positioned on the surface of the eye, preferably on the sclera. In some embodiments, options of positioning the ophthalmic device include one or more of: topical (sclera, cornea), subconjunctiva, conjunctiva, suprachoroidal, intraviteral, intra cameral, subretinal, or any other way to provide to the eye or onto or into other body parts. E.g., body caivities, (bladder, stomach) joints, etc. by intramuscular injection. In some embodiments, a potential advantage of positioning on the sclera is that the sclera is potentially less sensitive (to pain, irritation, etc.) than the cornea, so designing the matrix to contact only the sclera potentially results in a matrix that is more convenient for the user. In some embodiments, depending on the composition of the PVOH types included in the elastomeric matrix, complete degradation occurs, for example, between 0.5 hours and 12 hours from contacting the eye. Optionally from between 0.5 hours and 24 hours. Optionally between 0.5 hours and 48 hours. Optionally within longer than 48 hours. In some embodiments, a potential advantage of controlling the degradation time is that it allows a user to use the ophthalmic device during convenient and / or chosen hours (for example: while the user is sleeping, or for example to allow the device to act at a desired time window).

[0411] In some embodiments, the elastomeric matrix is characterized under dry conditions by a tensile strength below 10, 4, 3, MPa, preferably below 2 MPa. Additionally or alternatively, the elastomeric matrix is characterized under dry conditions by elasticity (aka Young Module) of 0.01 MPa to 10, 4, or 3 MPa, preferably O.OIMPa to 2MPa. Additionally or alternatively, the elastomeric matrix is characterized under dry conditions by an elongation at breakage of at least 50%, for example, 50% to 900% or 50% to 1000%. In some embodiments, a potential advantage to have a matrix characterized the above-mentioned mechanical properties is that it potentially reduces discomfort in the user, thereby potentially increasing compliance.

[0412] A broad aspect of some embodiments relates to an ophthalmic device, made with the elastomeric matrices as disclosed herein, for treatment and / or protection of the eye which, when positioned on an eye remains within the eye, e.g., between an eyelid and an eye surface. In some embodiments, the device stays on the eye for at least 15 minutes. In some embodiments, the device remains in the eye. For example, without moving from a region of the eye to which it has been positioned and / or without being expelled from the eye during a treatment time period. Where, in some embodiments, the device is positioned underneath the eyelid and / or on a portion of the eyeball. Whilst, in some embodiments, the device remains comfortable for a user to wear.

[0413] Preferably, the device does not cover even a portion of the cornea. Not touching the cornea may have an effect of reducing irritation (in comparison to devices that do touch the cornea), because the cornea is very sensitive to foreign bodies. In some embodiments, the device is configured to be put on the bulbar conjunctiva, which is relatively insensitive to irritation. A device configured to be worn on the bulbar conjunctiva may also be effective as it is relatively easy to wear and take off, in comparison to devices in other parts of the eye. In some embodiments, the device is in residence on the eye and / or remains in position (e.g. underneath an eyelid) during regular activities of a user / patient, for example, one or more of, blinking, tearing, crying, sweating, washing (e.g. showering), walking, exercising, sleeping. In some embodiments, the device is in residence on the eye and / or remains in position while the eyes are mainly closed e.g. during sleeping and / or for a semi-conscious or unconscious patient. In some embodiments, the ophthalmic device includes one or more active pharmaceutical ingredient (API) and / or other compound / s which are released (e.g. eluted from the device) while the device resides in the eye.

[0414] An aspect of some embodiments relates to an ophthalmic device, made with the elastomeric matrices as disclosed herein, which is configured to remain in position, underneath an eyelid of an eye. In some embodiments, optionally, part of the ophthalmic device remains in position underneath an eyelid of an eye while another part of the ophthalmic device extends outside the eyelid, optionally without reaching the cornea. In some embodiments, the ophthalmic device is configured to completely reside and remain between the surface of the eye and the eyelid. In some embodiments, the ophthalmic device does not comprise any part that extends outside the eyelid. In some embodiments, the device is configured to reside on a bulbar conjunctiva and underneath the eyelid, optionally, even during opening and closing of the eye (e.g. blinking).

[0415] In some embodiments, the ophthalmic device includes a retention portion which is sized and / or shaped to maintain the device underneath the eyelid. In some embodiments, the retention portion is the whole ophthalmic device. In some embodiments, the device have parts additional to the retention portion. In some embodiments, a device may include more than one retention portion. Where, in some embodiments, the retention portion is sufficiently thick and / or presents a sufficient height and / or a sufficiently steep slope to eye tissue that the device remains in position underneath the eyelid. For example, an anterior surface of the device presents a sufficient height and / or slope to eye tissue e.g. to an edge of the eyelid and / or to the tarsal plate.

[0416] In some embodiments, the thickness and / or height extends sufficiently in one or more directions. In some embodiments, the retention portion includes an anterior surface which presents a sufficient slope to eye tissue. In some embodiments, properties of the retention portion are dependent on one or more of a shape of the anterior surface at the retention portion, a thickness of the device (e.g. as defined between the anterior and posterior surfaces), a shape of the posterior surface. In some embodiments, when on an eye surface, the properties of the retention portion additionally depend on material properties (e.g. flexibility) of the device, for example as disclosed in relation to the exemplary elastomeric matrices disclosed herein, and the forces which the device experiences when in position on an eye surface and / or underneath an eyelid. In some embodiments, if the anterior surface of the retention portion is planar, the height of the retention portion is the same as a thickness of the device at the retention portion. In some embodiments, heights and / or slopes of the retention portion, in relation to the anterior surface, when in a dry configuration and / or a hydrated configuration, for example, are defined as for the device in a relaxed configuration and in relation to a plane on which the device rests, and / or on a plane connecting a majority of an edge circumference of the device. In some embodiments, heights and / or slopes of the retention portion, when in a dry configuration and / or a hydrated configuration, for example, are defined as for the device when in a relaxed configuration on a surface with radius of curvature (in one or more directions e.g. a sphere with the radius of curvature) of that expected of the eyeball onto which the device is to be positioned e.g. a radius of curvature of an adult human sclera, e.g. in both directions, e.g. radius of curvature of about 12mm. In some embodiments, heights and / or slopes of the retention portion, when in a dry configuration and / or a hydrated configuration, for example, are defined as for the device when on an eye surface where, in some embodiments, the device is deformed (e.g. flattened) by suction between the device and the eye surface and / or pressure onto the device (e.g. by the eyelid).

[0417] In some embodiments, height of portion / s of the device is affected by curvature of the posterior surface, the higher the curvature the higher the height, for a same thickness device. In some embodiments, the retention portion has a part with a sufficiently steep slope followed by a part with a sufficient thickness having a sufficient length, and / or area to allow retention of the device under the eyelid. Where, for example, the retention portion has heights with distance from the leading edge (or edge of the retention portion) as described herein and may also include a portion having a height higher than a holding height, where the portion has a sufficient extent to allow retention of the device under the eyelid. For example, the portion with the holding height may have an area of at least 1mm2, or 0.5-3mm2, or 0.5-2mm2. Where the holding height is 0.5- 5mm, or l-3mm. In some embodiments, a maximum height of the device is less than 3 times, or less than 2 times, or less than 1.5 times the holding height. In some embodiments, the device retention portion has a height of at least 1mm at 1mm inwards from an edge (e.g. leading edge) of the device and / or from an edge of the retention portion. In some embodiments, the device retention portion has a height of 50-2500 micrometers or 500-1000 micrometers at 0.5mm, or at 1mm, or 2mm from a leading edge of the device.

[0418] In some embodiments, the ophthalmic device comprises a body having a posterior surface, and an anterior surface. In some embodiments, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0419] A retention portion may be defined in between corresponding portions of the posterior and anterior surfaces. When the device is properly put in an eye, the posterior surface is adjacent the surface of the eye and the anterior surface is adjacent to an eyelid of the eye, defining heights above the eye surface.

[0420] Before being put in the eye, the device may be disposed in a relaxed configuration on a planar reference surface, with the posterior surface facing the planar reference surface. In such a position, the anterior surface defines heights above the planar reference surface. In some embodiments, the reference surface is defined as a surface (either real or imaginary) facing the posterior surface of a device in a relaxed configuration.

[0421] In some embodiments, two of said heights, measured from the eye surface and distanced from each other by a distance of at most 1mm, differ from one another by a height difference of at least 1mm. Alternatively or additionally, two of said heights, measured from the planar reference surface and distanced from each other by a distance of at most 1mm, differ from one another by a height difference of at least 1mm. In some embodiments, the reference surface is defined as a surface (either real or imaginary) facing the posterior surface of a device in a relaxed configuration.

[0422] In some embodiments, a first height measured from a first point on the posterior surface to a corresponding point on the anterior surface differs by at least 1mm, from a second height measured from a second point on the posterior surface to a corresponding point on the anterior surface, where the second point is distanced at most 1mm from the first point.

[0423] In some embodiments, the ophthalmic device comprises a body that comprises a posterior surface which is adjacent to an eye surface when the ophthalmic device is worn, an anterior surface which is adjacent to an eyelid when the ophthalmic device is worn. A retention portion may be defined by heights between the posterior surface and the anterior surface. In some embodiments, at least some of the heights between the posterior surface and the anterior surface differ from each other by at least 1mm when measured from two points on the posterior surface distanced from each other by at most 1 mm.

[0424] In some embodiments, the device retention portion is formed, at least partially, once the device is in the eye. For example, in some embodiments, the device crumples and / or squashes and / or folds to provide a retention portion. In some embodiments, under movement of the eyelid. In some embodiments, the retention portion of the ophthalmic device allows the ophthalmic device to remain between an eyelid and an eye surface. In some embodiments, when the ophthalmic device is positioned under the lower eyelid, the retention portion prevents the ophthalmic device from exiting the lower eyelid. In some embodiments, when the ophthalmic device is positioned under the upper eyelid, the retention portion prevents the ophthalmic device from exiting the upper eyelid.

[0425] In some embodiments, the retention portion is configured to prevent the ophthalmic device from sliding under an upper eyelid when the ophthalmic device is positioned (advertently or not) on the surface of the eye but not under either the lower eyelid or the upper eyelid (for example positioned in a location on the surface of the eye that is visible). Optionally, such retention portion allows the ophthalmic device to slide under the lower eyelid when a user closes his eyes. Thus, in some embodiments, a device residing on a visible portion of the eye may find its way to the bulbar conjunctiva and stay there, thanks to the retention portion.

[0426] In some embodiments, the device is thick, for example having a maximal and / or average thickness between the anterior and posterior surface of 400-2500microns, or of at least about 1mm. A potential advantage of such thicknesses (optionally, in combination with an extent of the retention portion and / or of the device) is a corresponding volume of the device which, in some embodiments, enables loading the device with therapeutic material. In some embodiments, the device has a volume of 1-500 microliters, or 1-100 microliters, or l-50microliters, or 10- 50microliters, or 20-100 microliters. Additionally, another potential advantage is that such thickness of the device, especially in a device made of a soft elastomeric matrix as described herein, potentially does not disturb the user, which potentially increases the compliance for the use of the device. In some embodiments, the device has a mass of l-500mg, or l-100mg, or l-50mg, or 10- 50mg, or 10-30mg, or 15-20mg, or 20-100mg. In some embodiments, the ophthalmic device includes l-500mg, or 20-500mg or 20-150mg, or 20-120mg of active pharmaceutical ingredient / s (API). In some embodiments, the ophthalmic device is formed of 1% to 50%, or 1-20% of active pharmaceutical ingredient / s (API). In some embodiments, an entirety or majority of the ophthalmic device is active pharmaceutical ingredient / s (API), for example, the device being at least 80%, or at least 90%, or at least 95%, or at least 99% active pharmaceutical ingredient (API), by weight and / or volume. In some embodiments, the ophthalmic device includes large amounts of active pharmaceutical ingredient / s (API) (e.g. about Img to about 20mg or more than Img, or more than 20mg, or 0.2-lmg, or l-4mg, or 4-10mg, or 10-20mg, or 20-50mg) and / or is able to elute such ingredient / s to a surface of the eye.

[0427] A potential advantage of the ophthalmic device is the ability to dispense active pharmaceutical ingredient (API), (e.g. a larger amount than that dispensed by topically applied preparation / s), to the surface of the eye and / or into the eyeball (potentially replacing eyeball injections). Where for example, a topically applied preparation having up to 1% concentration of active pharmaceutical ingredients (API) applied as eye drops, for example, 30 microliter is, 0.3mg where a significant portion of the active pharmaceutical ingredient (API) is expected to be flushed naturally out of the eye within a few minutes. A potential benefit of an ophthalmic device which elutes large amount of medication while residing on an eye surface is the ability to provide and / or maintain adequate concentration of drugs in intranasal regions and / or to the brain and / or to the head and / or to another target organ and / or the ability to provide systemic drug delivery (for example for dosing e.g. "micro dosing" of cannabinoids and / or opioids).

[0428] In some embodiments the device is used for recreational drug use.

[0429] In some embodiments, the retention portion of the device is a portion of the device adjacent to and, in some embodiments, including a leading edge of the device. Where, in some embodiments, the leading edge of a device is defined as a portion of a circumferential edge of the device which, when the device is underneath the eyelid, is nearest to an edge and / or opening of the eyelid. Without being bound by theory, in some embodiments, it is theorized that interaction between the tarsal plate of the eyelid with the slope of the device (and / or the retention portion of the device) acts to retain the device within the eyelid, behind the tarsal plate. In some embodiments, interaction between the tarsal plate and the device is associated with deformation of tissue of the eyelid around the device. In some embodiments, alternatively or additionally to force of the tarsal plate, reactive force of the tissue from deformation of the eyelid acts on the device to prevent movement of the device e.g. out of the eyelid and / or deeper into the cul-de-sac of the eye. Alternatively or additionally, in some embodiments, force between the eyeball and a posterior surface of the device acts to prevent movement of the device, where, in some embodiments, the force includes reactive force of pressure of the eyelid onto the device and then to the eyeball and / or suction forces between the device and eyeball. In some embodiments, the retention portion extends around the ophthalmic device, for example, 20-100% of a perimeter of the ophthalmic device. A potential advantage of a device having a retention portion which extends around a large proportion (e.g. more than 50%) of the device is increased retention forces on the device (e.g. of the tarsal plate) and / or in the event of device rotation, increased likelihood that the edge of the eyelid continues to interact with the retention portion.

[0430] In some embodiments, the ophthalmic device is symmetrical, for example, having rotational symmetry about one or more axes. For example, the ophthalmic device may be symmetrical about an axis perpendicular to an eye surface on which the device is disposed. Additionally or alternatively, the ophthalmic device may be symmetrical about a central axis e.g. a central axis defined as an axis connecting centers of the anterior and posterior surfaces. In some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.). A potential advantage of rotational symmetry being maintaining of retention portion interaction with the edge of the eyelid and / or tarsal plate if the ophthalmic device rotates while being worn within the eye.

[0431] In some embodiments, the ophthalmic device includes more than one retention portion. A potential advantage of multiple retention portion may be increased area of retention portion / eyelid interaction to hold the device in position. A potential advantage of such increased area may be that if a first retention portion fails and the device escapes from underneath the eyelid and / or the first retention portion escapes from underneath the tarsal plate, the ophthalmic device is potentially retained at least partially underneath the eyelid by a second retention portion. A potential advantage of having more than one raised portion of the device (e.g. as provided by retention portions) is that raised surfaces ease pinch-removal. Pinch-removal being, in some embodiments, where two opposing forces are applied on different portions of the device to break suction between the device and the eye surface and / or push portion / s (e.g. between the portions to which the forces are applied) of device away from the eye surface. Where, in some embodiments, the opposing forces are applied manually by a user e.g. by a thumb and other finger e.g. index finger.

[0432] In some embodiments, an ophthalmic device including a plurality of retention portions includes one or more cavities on a posterior surface of the device e.g. a cavity for each retention portion.

[0433] In some embodiments, for example, where the device is symmetrical, the retention portion is formed by entire edge of the device or a large proportion e.g. at least 50%, or at least 80% or at least 90% of the perimeter of the device. A potential benefit of all or a large proportion of edges of the device being increased likelihood of retention of the device underneath the eyelid in the circumstance of rotation of the device.

[0434] In some embodiments, the ophthalmic device is configured to adhere to an eye surface onto which it is positioned. In some embodiments, if the device escapes from underneath the eyelid, partially or fully, adhesion forces of the device to the eye surface (e.g. sclera) are sufficient to maintain the device on the eye, e.g. for at least a short period of time e.g. during blinking (in some embodiments, during a few blinks e.g. 1-10). Where, in some embodiments, upon escape and / or emergence of the device from underneath the eyelid, the device is returned (e.g. manually) to underneath the eyelid. In some embodiments, adherence of the ophthalmic device to an eye surface is sufficient to prevent rotation of the device. For example, for devices which are not rotationally symmetrical and / or for devices which have a localized retention portion and / or a retention portion disposed asymmetrically on the device. In some embodiments, adherence of the ophthalmic device to an eye surface (e.g. sclera) is associated with suction forces between the device and the eye surface. For example, in some embodiments, a posterior surface of the ophthalmic device adjacent to the eye surface is curved, e.g. is concave, in one or more directions. The curve potentially increasing suction forces between the device and the eye surface. In some embodiments, a curvature of the posterior surface is 0.1-1 that of the sclera, in one or more directions. In some embodiments, a radius of curvature of the posterior surface, in one or more directions, is l-15mm, or l-10mm, and / or has a ratio to that of the sclera being 0.1-2, or 0.5-1.

[0435] In some embodiments, a lower curvature of the posterior surface is associated with reduced suction forces between the eye surface and the posterior surface, potentially enabling re-positioning and / or increasing comfort to a user. In some embodiments, a radius of curvature of the posterior surface, in one or more directions, is lower than that of the sclera, for example a ratio of the radius of curvature of the posterior surface to that of the sclera being greater than 0.8, for 3exmaple between 0.8 and 1. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0436] In some embodiments, different portions of the posterior surface have different radii of curvature, but, in some embodiments, each of these have a curvature lower than that of the sclera. In some embodiments, dimensions and / or ratios thereof (e.g. curvatures) as described in this document relate to average adult human eye curvatures. Where, for example, in some embodiments a radius of curvature of the sclera, RS is about 12mm. In some embodiments, dimensions and / or curvatures are selected for different anatomies, for example for a child’s eye, for example for an animal eye, for example for a different surface (e.g. mucosal surface). Where, for example, when the device is used in an eye having different dimensions and / or curvatures (e.g. animal eye, child's eye) size / s and / or curvature / s of the device are scaled for use in the eye type and / or in a specific eye (e.g. personally tailored devices). For example, where one or more dimension of the device e.g. length and / or width of the device footprint and / or retention region height and / or slope (e.g. as described within this document) is scaled, for example, using one or more measurement parameter of the eye in question e.g. a radius and / or diameter and / or largest extent of the eye.

[0437] In some embodiments, for example, where the surface includes cavity / ies and / or protrusion / s and / or has a surface texture, radius of curvature of a surface (and / or edge and / or corner) is defined as a radius of a circle which matches curvature of at least 60%, or 80% or 90% of the surface (and / or edge and / or comer). In some embodiments, the ophthalmic device includes multiple layers and / or portions with different material properties. In some embodiments, the device includes one or more of a lubricous layer, a mucoadhesive layer and an additional layer. In some embodiments, one or more layer includes therapeutic material. In some embodiments, a body of an ophthalmic device has a concave posterior surface. In some embodiments, concavity of a posterior surface in contact with the eye surface (e.g. sclera), increases adhesion of the device to the eye surface. The concavity, for example, providing suction force between the device and eye surface, adhering the device to the eye surface.

[0438] Optionally, in some embodiments, a radius of curvature of one or more portions of the posterior surface of the device is smaller than that of the portion of the eye to which the device is to be adhered to. For example, the sclera. In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made of a continuous material, meaning it does not comprise macroscopic gaps and / or empty areas within it. In some embodiments, a gap or empty area is defined as macroscopic if it is larger than 0.2mm. In some embodiments, the body of the ophthalmic device has an oval or round form. In some embodiments, the body of the ophthalmic device is symmetrical relative both to its longitudinal axis and relative to its transversal axis. For example, when looking at the ophthalmic device from the anterior surface, the device is symmetrical relative to its longitudinal axis and relative to its transversal axis.

[0439] In some embodiments, the device has an elliptical and / or oval cross-sectional shape. For example, the posterior surface may be elliptical and / or oval.

[0440] In some embodiments the posterior surface is smooth for example, potentially reducing irritation associated with contact between the eye surface and the device. In some embodiments, the posterior surface includes rough portion / s and or anchor / s potentially increasing adhesion by friction between the posterior surface and the eye surface. In some embodiments, edge regions (e.g. and optionally, in some embodiments, not a central region which is smooth) of the posterior surface are rough and / or include anchor / s and / or protrusions and / or cavities. In some embodiments, the posterior surface is smoother than the anterior surface. In some embodiments, both the posterior surface and the anterior surface are similarly smooth. In some embodiments, a device includes one or more feature to increase adherence between the device and the sclera. For example, roughness and / or anchors (e.g. cavity / ies, protrusion / s and / or hook / s) for example, located at a posterior surface and / or at edges of the device.

[0441] An aspect of some embodiments relates to an ophthalmic device, made of elastomeric matrices as disclosed herein, configured to remain underneath an eyelid (for example, having a retention portion) but that has mobility and / or allows fluid flow between the device and an eyeball surface. A potential advantage of mobility or fluid flow between the device and the eyeball being increased user comfort and / or reduced risk of bacterial growth underneath the device (e.g. associated with tear fluid exchange). In some embodiments, mobility of the device on the eye surface is associated with low suction between and / or an easily breakable suction seal between a posterior surface of the device and the eyeball surface. For example, in some embodiments, the posterior surface includes one or more portions which is has low concavity (e.g. with radius of curvature as described above), or is not concave, or is convex, potentially reducing the ability of the device to seal with the eyeball surface. In some embodiments, the device is able to form a seal with the eyeball surface, for example, having convex posterior surface and / or flexible edges where the seal is easily broken e.g. to allow the device to move on the eye surface (e.g. periodically). For example, in some embodiments, the device includes a sealing edge (e.g. flexible) only on a portion of the device. For example, in some embodiments, the device is elongate, potentially easing breaking of suction forces between the device and the eye surface. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0442] An aspect of some embodiments of the invention relates to an ophthalmic device, made of elastomeric matrices as disclosed herein, which maintains size and / or shape both in storage and in use where, in some embodiments, the device is provided in a dry form and optionally hydrates during residency on an eye surface. A potential benefit being reduced distortion of the device during hydration and / or use and / or maintained shape and / or maintained mechanical characteristics of the device during use. For example, while being able to store the device in a dry form where active pharmaceutical ingredient / s (API) are less likely to be degraded and / or degrade less rapidly e.g. potentially increasing shelf life of the device. In some embodiments, as the device hydrates (e.g. on an eye surface) the device increases in volume by less than 20%, or less than 15%, or less than 10%, or less than 5%. In some embodiments, one or more maximal cross sectional dimension as the device hydrates increases by less than 20%, or less than 15%, or less than 10%, or less than 5%.

[0443] An aspect of some embodiments of the invention relates to an ophthalmic device, made of elastomeric matrices as disclosed herein, which, when dry and when hydrated is soft. Where, in some embodiments, the device is provided in a dry form and optionally hydrates during residency on an eye surface. A potential advantage of a soft device in dry form, is enabling application of the device to the eye without prior hydration and / or softening. A potential benefit of a soft ophthalmic device is reduced irritation to the eye e.g. reducing tearing associated with presence of the device which, in some cases, flushes therapeutic material and / or nutrients.

[0444] In some embodiments, as further disclosed below in relation to the elastomeric matrices of the ophthalmic device, at least a portion of the ophthalmic device degrades and / or disintegrates within the eye. In some embodiments, degradation is by loss of mass. In some embodiments, the ophthalmic device is a biocompatible device which is designed to be partially or completely biodegradable and / or bioerodible. The term biodegradable is to be understood as going degradation in the living body, for example, by change of mechanical properties, mass loss, and / or change of shape. Chemical decomposition of the polymers in the matrix is not necessary in order to achieve degradation. Optionally, the PVOH itself remains in its original length, and bonds (e.g. hydrogen bonds) between PVOH, plasticizers, and water break. In some embodiments, the degradation allows clearing the ophthalmic device, or the elastomeric matrix it comprises, from the eye, for example, by tears, that may wash the matrix constituents, crumbs, and / or remains out of the eye. For example, in some embodiments, a portion of a device degrades e.g. once the device is adhered to the eye surface. The degrading one or more portions may include, for example one or more mucoadhesive portions and / or one or more lubricous portions. For example, in some embodiments, one or more portions of the device is selected to degrade within the eye, in about 1 minute to 30 minutes or 15 minutes to 1 hour or about 0.5 hour to 8 hours, or 4 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.

[0445] In some embodiments, one or more portions of the ophthalmic device degrade to enable eluting of therapeutic material. For example, in some embodiments, as a portion comprising therapeutic material degrades, it elutes the therapeutic material into eye tissue and / or eye fluid. For example, in some embodiments, a portion degrades to reveal a portion comprising therapeutic material. Where, in some embodiments, the degrading portion initially covers at least a portion of the portion comprising therapeutic material. In some embodiments, at least a portion of the device is degraded and / or its properties are deteriorated when exposed to a biological environment, for example, a biological system e.g. the eye, and / or to a similar in vitro environment simulating conditions of a biological system.

[0446] In some embodiments, degradation and / or deterioration of the device is manifested by change (e.g. reduction) in one or more of device's physical properties, for example one or more of device integrity, tensile strength, elastic module, elongation at breakage, etc.

[0447] In some embodiments, degradation occurs from the posterior surface towards the anterior surface, for example, the device maintaining a shape of the anterior surface, for a portion of time during which the device is degrading. In some embodiments, degradation from the posterior surface is more rapid than that of the anterior surface. In some embodiments, the device includes different portions which degrade at different rates. In some embodiments, lower speed degrading and / or non-degrading portions acting to maintain a shape (e.g. retention portion shape) for a time period. In some embodiments, the device is designed to break into portions, for example, upon application of manual pressure. Where, in some embodiments, a size and / or shape and / or brittleness of the device is selected to provide this feature. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0448] An aspect of some embodiments of the invention relates to an ophthalmic device, made of elastomeric matrices as disclosed herein, having one or more retention portions, and including a thin and / or conforming edge portion. In some embodiments, for example, where the device includes a thin edge portion and / or portion extending from a body of the device, the retention portion is defined as a region of the device fulfilling the requirements of height and / or slope e.g. as described above. In some embodiments, the device (e.g. curvature of one or more portions of the device e.g. to generate sufficient suction to hold the device in position) conforms to an eye. Where, for example, in some embodiments, an edge portion is sufficiently thin and / or flexible to conform to a surface of the eye. In some embodiments, the device has thin edges and / or edges of the device recessed into a surface of the eye. In some embodiments, moving from a leading edge of the device, the device includes a thin edge followed by a retention portion. In some embodiments, a step formed between an edge of the device and the eye surface, for example, by the thin edge next to the retention portion, is l-100microns, or 10-50microns. In some embodiments, edge characteristics (e.g. shape and / or thickness) as described in this document are for all of or a portion of an edge region of the device. For example, a portion of a circumferential edge of the device. For example, for 20-99%, or 80-90%, of a circumference of the device. In some embodiments, different portions of a circumferential edge of a device have different properties e.g. shape and / or thickness.

[0449] In some embodiments, adherence to the sclera is associated with adherence of edges of the device to the sclera, for example influenced by an extent of conforming of the device to the sclera and / or of the sclera to the device. In some embodiments, flexibility and / or elasticity of the device increases sealing between the device edge and the eye surface. In some embodiments, the device includes one or more edge portion which is flexible and / or elastic e.g. sufficiently thin to be flexible. In some embodiments, the device has an edge designed for user comfort and / or to increase adherence to the eyeball. In some embodiments, the ophthalmic device has a thin edge. In some embodiments, an edge (e.g. circumferential edge) of the device has 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 a thin edge 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. In some embodiments, for example, alternatively to having a thin edge. Or where, a device, in some embodiments, has an edge circumference where only a portion of the circumference is thin, in some embodiments, the edge of the device is blunt and / or curved and / or rounded for example, increasing comfort of wear for a user. In some embodiments, the edge of the device is sharp e.g. chisel shaped and / or knife edged. In some embodiments, the edge of the ophthalmic device is defined as a 0.1-lmm edge region, or 0.1-0.5mm edge region of the device. In some embodiments, an edge thickness is measured at 0.1mm, or 0.5 mm, from a circumference of the device. In some embodiments, a thin edged device provides improved sealing between edges of the device and the eye surface. A potential advantage of sealing between the device edges and the eye surface is increased suction between the device and the eye surface.

[0450] A potential advantage of sealing between the device edges and the eye surface is reduced accumulation of debris (e.g. one or more protein, mucus, oil, and skin cells) of between the device and the eye surface potentially minimizing risk of infection associated with use of the ophthalmic device.

[0451] In some embodiments, a thin edged device conforms to a shape of the eye surface at the device edges. In some embodiments, an edges of the device provide anchoring of the device into the eye surface e.g. soft tissue of the conjunctiva e.g. the soft and thick scleral conjunctiva which is apparently, about 25-40 microns thick and is apparently even thicker in the fornix. In some embodiments, the device recesses into the eye surface at edges of the device and / or makes an indentation in the eye surface, for example, the recessing associated with one or more of pressure between edges of the device and / or softness of the eye surface. In some embodiments, portion / s of the eye are deformed in depth (e.g. by the device), for example at edges of the device (and / or at region / s adjacent to protrusions and / or cavities of the device) e.g. by 50 microns to 500 microns.

[0452] In some embodiments, tissue local to edges of the device deforms, for example, a region of tissue at most 0.5mm, or 1mm. In some embodiments, edges (and / or edge region / s) of a device conform to a shape of the eye surface. For example, in some embodiments, edge region / s are flexible and / or elastic and / or sufficiently thin to conform to the eye surface. In some embodiments, a device body is flexible and / or elastic e.g. sufficiently flexible and / or elastic to conform to the eye surface, at least partially. Potentially, device body and / or edges conforming to the eye surface improves user comfort and / or reduces risk of dislodgement of the device.

[0453] In some embodiments, the posterior surface includes one or more cavities or protrusion, for example, on the posterior surface of the device. Without being limited by theory, it is hypothesized that, in some embodiments, a cavity increases suction between the device and the eye surface e.g. localized suction at the cavity. In some embodiments, eye tissue enters the cavity (e.g. under suction forces of the cavity), potentially increasing adherence between the device and the eye. A potential advantage of cavity / ies on the posterior surface is extended residence time of the device on the eye.

[0454] In some embodiments, the device has a plurality of cavities, where in some embodiments, two or more of the cavities are about the same size and / or shape. Where, in some embodiments, two or more of the cavities are different from each other, for example, in size and / or shape. In some embodiments, an opening size of a cavity, is between 0.005mm and 20 mm, or 0.005-2mm, or 0.005-lmm, or 0.005-0.5mm, or l-2mm, l-4mm, or 2-6mm 3-8mm, or 4-10 mm, or 5-20mm. In some embodiments, a cavity has a large opening, for example, extending over at least half of an area of the surface (e.g. posterior surface) and / or having an extent of l-10mm, or l-8mm, or 1- 5mm, or 5-20mm. In some embodiments, an aperture of a cavity is macroscopic or microscopic in size. In some embodiments, a depth of a cavity is 5 microns-2 mm, or 5 microns -1 mm, or 5-400 microns, or 5-200 microns, 200-600 microns 400-800 microns 600-1500 microns 800-2000 microns. In an exemplary embodiment, a depth of a cavity is 400-1200microns. In some embodiments, a cavity extends through a proportion of a thickness of the device, for example, through at 10-20% 20-30% 30-50% 50-90%, or 80-99%, or 90-99%, 50-70%, 60-90%, of a thickness of the device in a region of the cavity.

[0455] In some embodiments, the ophthalmic device includes one or more protrusions from one or both surfaces of the device. In some embodiments, protrusion / s have a rounded and / or blunt shape. In some embodiments, the device has a plurality of protrusions, where in some embodiments, two or more of the protrusions are about the same size and / or shape. Where, in some embodiments, two or more of the protrusions are different from each other, for example, in size and / or shape. In some embodiments, a size of a protrusion, above a surface (e.g. posterior and / or anterior) of the device is 5-400 microns, or 20-200 microns, or 200-800 microns or 400-1200 microns or 600-1500 microns lower or higher or intermediate ranges or sizes. In some embodiments, an extent of a footprint of a protrusion on the surface of the device is 5microns to 3mm, or 5 microns to 1mm, or 5-700microns, or 5-400microns or 3-6mm, or 4-8mm, or 4- 10mm, or 6- 12mm.

[0456] A potential benefit of protrusion / s is increased adherence of the ophthalmic device to the eye surface. In some embodiments, protrusion / s increase friction between the eye surface and the eye surface. In some embodiments, protrusion / s increase (e.g. between the protrusions) increase the suction force between the device and the eye surface. In some embodiments, the ophthalmic device includes mucoadhesive material e.g. on the posterior surface of the device which potentially increases adhesion between the device and the eye surface on which the device is positioned.

[0457] Optionally, in some embodiments, the posterior surface includes one or more mucoadhesive part. Where mucoadhesive material / s in some embodiments, increase adhesion of the device to the eye surface. In some embodiments, the posterior surface includes a mucoadhesive layer. Where, in some embodiments, the layer covers the posterior surface. Alternatively, in some embodiments, the mucoadhesive layer is a non-continuous surface, where hole / s, for example, allow water penetration and / or drug transportation e.g. to a layer underneath the mucoadhesive layer. In some embodiments, the mucoadhesive layer has a ring-shape including an aperture in the center e.g. enabling water penetration and / or drug transportation. The mucoadhesive layer in the device, in some embodiments, is provided dry and / or semi-hydrated. Where, in some embodiments, upon application of the device to the eyeball, the mucoadhesive layer hydrates and becomes sticky, for example, in less than 10 seconds, or in less than 30 seconds, or in less than 1 minute. In some embodiments, the material / compound / polymer in a mucoadhesive layer has an adherence force of 80-200%, or of 100-200%, or of over 100%. Where, for example, pectin is defined as having an adherance force of 100%. In some embodiments, mucoadhesive portions include at least one mucoadhesive compound, which in some embodiments, is selected from the group consisting of gelatin, alginates, chitosan, amylose, collagen, sodium poly-acrylate, modified starch, elastin, polyacrylic acid and combinations thereof. In some embodiments, the device presents a low friction surface to the eyelid (e.g. is smooth). A potential advantage of which is reduced likelihood of dislodgement of the device. In some embodiments, the device presents a low friction surface to the eye surface (e.g. is smooth). A potential advantage of which is reduced likelihood of discomfort to the user. In some embodiments, the device presents a same low level of friction to the eyelid and to the eye surface.

[0458] Optionally, in some embodiments, one or more of portion of an anterior surface of the device is smooth and / or includes lubricious material. Where the anterior surface of the device is a surface which is in contact with the inner surface of the eyelid, at least part of the time. Potentially, in some embodiments, smooth and / or lubricous material reduces friction between the eyelid and the surface. Potentially, in some embodiments, the smooth and / or lubricous material minimizes irritation of the eye, e.g. the eyelid, e.g. associated with the ophthalmic device.

[0459] In some embodiments, the posterior surface is smoother than the anterior surface. In some embodiments, both the posterior surface and the anterior surface are smooth. In some embodiments, a lubricious material layer covers the anterior surface where, in some embodiments, the layer is continuous. In some embodiments, the lubricious layer is a non-continuous surface, (e.g. including one or more hole) for example to allowing water penetration and / or drug transportation. For example, in some embodiments, a lubricious material layer includes holes. In some embodiments, the anterior surface hosts one or more lubricious material portion where, in some embodiments, one or more of the portions is connected to other portion / s and / or one or more of the portions is not connected to other portions. Optionally, in some embodiments, the lubricous surface is temporary, where, in some embodiments, one or more portions of lubricous material degrades and / or disappears (e.g. is absorbed and / or expelled by the eye), for example, before other portion / s of the device degrade. In some embodiments, a material layer has variable thickness and / or variable material properties e.g. a lubricious layer and / or a mucoadhesive layer. Where, for example, upon attachment to the eye, a material has a larger extent on the anterior surface than after a time period of residence on the eye, where, in some embodiments, more rapidly degraded portion / s (e.g. thinner portions and / or portions having more a rapidly degraded composition) of the layer dissolve prior to other portion / s e.g. to reveal lower layers which in some embodiments comprise active pharmaceutical ingredient / s (API). While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0460] An aspect of some embodiments of the invention relates to a kit comprising an ophthalmic device (e.g. as described in this document and made with elastomeric matrices as disclosed herein) and instructions for use thereof. In some embodiments, the kit comprises means for delivering the device into the eye of a patient. For example, an applicator. In some embodiments, the ophthalmic device is packaged together with the applicator. Optionally, in some embodiments, the kit includes a degradation formulation which, when contacted with the device when the device is on an eye surface of a patient, structurally degrades the device and / or accelerates degradation of the device. In some embodiments, devices are provided in multi-device packs. Where, in some embodiments, two or more devices are interconnected to one another, or separated.

[0461] In some embodiments, the ophthalmic device is one or more of flexible, elastic, and supple e.g. to conform to a shape of the eyeball. In some embodiments, the ophthalmic device elasticity and / or softness is similar to the elasticity and / or softness of soft contact lenses. In some embodiments, the ophthalmic device has elasticity or softness, in one or more directions, with a Young’s modulus of 0.01-1.5MPa or 0.05-0.15-1.5MPa, or 0.25-0.35MPa. In some embodiments, as mentioned before, the required softness may be achieved with an elastomeric matrix formulated with water, PVOH, and a large amount plasticizers. The amount of the plasticizers may be considered large if it is larger than, or, preferably, at least double (in mass) than the mass amount of the PVOH. In some such embodiments, the mass of the PVOH and the plasticizers together is 70% or more of the total mass of the matrix excluding the water. In some embodiments, the ophthalmic device has elasticity, in one or more directions, with a Young’s modulus of 0.01- 2.00MPa. In some embodiments, the ophthalmic device has elasticity, in one or more directions, (e.g. Young’s modulus 0.01-200MPa, or 0.05-0.15MPa or 0.15-0.35 MPa) in a dry form. In some embodiments, the ophthalmic device has elasticity, in one or more directions, (e.g. Young’s modulus 0.01-200MPa, or 0.05-0.15MPa, or 0.01-0.35MPa) in a wet form while in the eye. In some embodiments, the ophthalmic device has elasticity allowing elongation of 10% to 800% or more (in dry form and / or in wet form). In some embodiments, the ophthalmic device is one or more of rigid, and shaped e.g. shaped to conform to a shape of the eyeball. In some embodiments, the ophthalmic device elasticity and / or hardness, in one or more directions, similar to the elasticity and / or hardness of hard or rigid contact lenses. In some embodiments, the ophthalmic device has elasticity, in one or more directions, with a Young’s modulus of 0.1-200MPa. In some embodiments, the ophthalmic device has this elasticity, in one or more directions, when in a dry form. In some embodiments, the ophthalmic device has this elasticity in the wet form e.g. while in the eye. In some embodiments, the ophthalmic device has layers with different material properties e.g. elasticity and / or flexibility (see below regarding exemplary elastomeric matrices of the ophthalmic device). In some embodiments, the ophthalmic device has regions having different material properties e.g. elasticity and / or flexibility. In some embodiments, the device is flexible, potentially enabling the device to shape to a surface of the eye e.g. potentially increasing user comfort (e.g. allowing the eyelid to move smoothly above the device with little or no interference and / or discomfort) and / or reducing dislodgement forces experienced by the device. In some embodiments, a flexible device has a concave posterior surface, where suction (e.g. associated with interaction between concavity of the posterior surface and the eye surface) between the device and the eye surface then flattens the device onto the eye surface. In some embodiments, elasticity of the device increases suction force between the device and the eye surface to adhere the device to the eye. Where, for example, in some embodiments, elasticity compensates for low concavity curvature of the posterior surface of the device. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0462] In some embodiments, flexibility and / or elasticity of the device increases sealing between the device edge and the eye surface. In some embodiments, one or more portions is configured to fit an eye surface and / or a portion of an eye surface and / or an orifice. In some embodiments, the device is selected to be compatible with size of the inferior or superior conjunctival sac where the device deforms the sac only slightly, for example, by at most 2mm for example, by only an amount which is comfortable for a user and / or does not cause harm to the eye surface and / or eyelid and / or other tissue / s. For example, in some embodiments, only the retention portion deforms the sac. It has been found that devices with a height of 2mm can be comfortable and, in some embodiments, up to a height of 4-6mm. It has been found that, in some embodiments, a device width of 5- 10mm is comfortable. In some embodiments, the ophthalmic device has a thickness of less than 3mm, or less than 2.5mm, or less than 2mm, or less than 1.5mm, or less than 1mm, or less than 0.8mm, or less than 0.6mm, or less than 0.5mm, or less than 0.4mm, or less than 0.3mm. In some embodiments, the ophthalmic device has a thickness of greater than 3mm, or greater than 2.5mm, or greater than 2mm, or greater than 1.5mm, or greater than 1mm, or greater than 0.8mm, or greater than 0.6mm, or greater than 0.5mm, or greater than 0.4mm, or greater than 0.3mm.

[0463] In some embodiments, pressure between the eye and the device is increased by increasing the thickness of the device and / or the thickness of an edge region of the device. Where, increased pressure (and / or sealing between the eye and the device e.g. associated with pressure and / or contouring of the eye to the device or the device to the eye) in some embodiments, reduces tear fluid penetrations between the device and the eye surface.

[0464] In some embodiments, the device is small e.g. sufficiently small that it fits within a space underneath an eyelid (e.g. entirely). In some embodiments, a maximum and / or average extent of a device is about 4- 12mm, or 4- 10mm, or 4-8mm, or 3-8mm, l-8mm, or 4-6mm. In some embodiments, the ophthalmic device has a size (e.g. maximum and / or average extent) of about 4mm. In other embodiments, the device has dimensions of between about 0.5 to about 20 mm in maximum size. A potential advantage a small dimensioned device is increased user comfort and / or lower likelihood of dislodgement of the device during movement of an eyelid over the device.

[0465] In some embodiments, an ophthalmic device is elongated. Where, for example, in some embodiments, a dimension of the device measured along an axis of the elongation is about 0.5- 20mm. In some embodiments, the ophthalmic device is designed to be put in and out of the eye by the patient wearing it. In some such embodiments, the device is at least 3mm long along its shorter side, to allow the user to see it and manipulate it conveniently when putting the device under the eyelid. In some such embodiments, the dimension of the device measured along an axis of the elongation is larger than 3mm, for example, at least 4mm or at least 5mm. On the other hand, the device is preferably not too large, so as not to bother the wearer, so a maximum extent may be in some embodiments, about 8mm. Where, in some embodiments, an extent of the device is measured as a maximum dimension of a smallest cuboid shape into which the device fits. In some embodiments, for example, associated with low curvatures of the device surfaces, the cuboid bounding shape is thinner in one dimension, (e.g. associated with a direction into the eye when the device is on the eye) than in the other two dimensions.

[0466] In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made of a continuous material, meaning it does not comprise macroscopic gaps and / or empty areas within it. In some embodiments, a gap or empty area is defined as macroscopic if it is larger than 0.2mm. In some embodiments, as shown for example in Figure 6A, the body of the ophthalmic device is symmetrical relative to its longitudinal axis (schematically shown by line AA) and relative to its transversal axis (schematically shown by line BB). For example, when looking at the ophthalmic device 600 from the anterior surface, the device is symmetrical relative to its longitudinal axis (AA) and relative to its transversal axis (BB). In some embodiments, for example, in the embodiment schematically illustrated in Figure 6A, the symmetries in relation to both axes are mirror reflection symmetry. In some embodiments, the device comprises an elliptical and / or oval cross-sectional shape. A potential advantage of the symmetry of the ophthalmic device is convenience of use where, in some embodiments, the device is applied by the user himself, and having no “wrong” orientation may increase convenience of use.

[0467] In some embodiments, an ophthalmic device as described herein may be used once to deliver active pharmaceutical ingredients (API) and / or to provide active pharmaceutical ingredient (API) availability for a time period longer than that of topically applied preparations such as eyedrops, which are typically available for less than a minute. Some embodiments provide drug delivery for a time period of about 5 minutes or longer, or longer than 10 minutes, or longer than an hour, or longer than a day. Where, in some embodiments, the device serves as controlled release vehicle for one or more active pharmaceutical ingredients (API).

[0468] A potential benefit of an ophthalmic device configured to reside on an eye surface is potentially increased residence time of a treatment drug in the eye. For example, as compared to periodically applied topical compositions (e.g. eye drops, ointment). A potential benefit of an ophthalmic device which elutes medication while residing on an eye surface is the ability to provide and / or maintain adequate concentration of drugs in the pre-comeal / pre- scleral tear film e.g. for extended periods of time, for example, of from 5 minutes to 24 hours or more. A potential benefit of an ophthalmic device which elutes medication while residing on an eye surface e.g. maintaining a position on the eye surface is the potential ability for medication to diffuse through eye tissue. For example, penetrating into the sclera and / or into the cornea and / or into the eyeball, and / or reaching more internal portion / s of the eye. Potentially enabling, in some embodiments, topical medication of those areas which are usually treated by injection e.g. into the eyeball. A potential benefit of an ophthalmic device (e.g. with extended residence and / or elution times) is the ability to provide and / or maintaining adequate concentration of drugs to intranasal region / s (e.g. as delivered by tear fluid) and / or to the brain and / or to the head and / or to another target organ and / or as systemic drug delivery.

[0469] In some embodiments, the ophthalmic device being in residence enables steady elution of treatment materials into the eye potentially reducing effects of periodic dosing of eyedrops or ointments such as, for example, a transient period of systemic and / or local overdose (potentially associated with high risk of side effects) followed by an extended period of sub-therapeutic levels before the administration of next dose. Where the rate of tissue drug uptake is high at early times after dosing, but declines rapidly. A long residence time, for example, as compared to, eye drops applied to the eye e.g. the surface of the eyeball, where blinking and natural tear flow combine to limit time that liquid medicament will remain effective e.g. to a few minutes. Potentially, less active pharmaceutical ingredient (API) per treatment is used in treatment of a subject using an ophthalmic device e.g. as opposed to topical preparations where active pharmaceutical ingredients (API) may be washed out before they are effective requiring higher quantities of active pharmaceutical ingredients (API) and / or where high patient compliance is more likely to be lower as application is frequent potentially resulting in more discarded un-used active pharmaceutical ingredients (API). In some embodiments, the ophthalmic device protects a portion of the eye. For example, from external impact / s and / or chemical changes. For example, to ameliorate and / or reduce ocular damage upon orbisculation (citrus fruit squirting juice into the eye). In some embodiments, the ophthalmic device protects a portion of the eye, enabling 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. Where, suction forces in between the eye surface and the device, potentially assisting in closing and / or maintaining closure of the incision and / or wound potentially hastening healing.

[0470] In some embodiments, a device is tailored to an individual subject, where, for example, in some embodiments, one or more of size, shape, curvature of surface / s, type of therapeutics, release time, residence time are selected for the individual and / or according to an individual treatment plan. Although throughout this document, ophthalmic use of the device is described, it should be understood that one or more embodiments and / or combinations of embodiments of the device as described within this document, in some embodiments, are used in treatment of other portions of a human or animal body. For example, for portions of the eye other than the sclera, e.g. the cornea, the cul-de-sac of the eye. For example, other mucosal surface / s e.g. the inner mouth e.g. the intranasal surface. For example, other tissue types and / or organs. Although throughout this document, ophthalmic use of the device is described, it should be understood that one or more embodiments and / or combinations of embodiments of the device as described within this document, in some embodiments, are used for other applications such as: to host e.g. contain, have attached to and / or provide a support for one or more type of electronics e.g. on the eye. For example, one or more active electronic element and / or passive modules and / or components e.g. an antenna, RFID. For example, one or more capacitor and / or resistor and / or, shape memory element, or may act as a support for other element or elements in the ocular region etc.) Where, for example, in some embodiments, electronics include on or more of sensor / s (e.g. temperature sensitive element, pressure sensitive element, humidity sensitive element), imager / s (e.g. camera), a user interface, a processor, transmitter, receiver, illumination element, led screen, power source. In some embodiments, electronics (e.g. using sensor / s) are used for therapeutics (e.g. Electroconvulsive therapy (ECT) treatment) and / or diagnostics. In some embodiments, one or more electronic part is used for entertainment (e.g. VR) and / or aesthetic enhancement. In some embodiments, the device is used for entertainment and / or for aesthetic enhancement. In some embodiments, more than one device as described in this document is used to treat a subject, for example, where multiple devices are in situ on an eye surface at the same time, for example, each device providing a particular dose. Where, in some embodiments, to provide a higher dose more than one device is applied. In some embodiments, multiple devices as described in this document are provided packaged together and / or where the multiple devices are provided connected. In some embodiments, the device includes and / or is constructed from non-toxic and / or biocompatible materials. In some embodiments, where therapeutic material is toxic in high concentrations, the entire device, in some embodiments, contains less than a toxic dose and / or the device elutes the therapeutic material at sub-toxic levels. In some embodiments one or more portions of the device include dye and / or pigment e.g. for ease of identification while in the eye, and / or during insertion and / or extraction, and / or during production. In some embodiments, dye and / or color is printed into one or more identifying shape and / or letter and / or numeral and / or barcode. In some embodiments, one or more identifier is embossed or stamped on the device. In some embodiments, the device includes one or more electronic identifier e.g. RFID on or within a body of the device. In some embodiments, device dye and / or pigment includes one or more of blue, red, fluorescent yellow, and / or any other color. In some embodiments, the ophthalmic device is manufactured from a film, for example, a multi-layer film. Where, in some embodiments, the film is cut into shape to form individual devices. In some embodiments, the film and / or individual devices are shaped for example, to form desired curvatures of surfaces. Where, in some embodiments, shaping is by casting of a solution onto a shaped support surface e.g. a mold. Where, in some embodiments, shaping is by application of mechanical and / or chemical treatment e.g. pressure and / or heat. Thus, in some embodiments, the ophthalmic device is obtainable by mixing the API with water and ophthalmic demulcents to obtain a mother solution; and drying the mother solution at room temperature, optionally in a mold shaped according to the desired shape of the device. In some such embodiments, the ophthalmic device is obtainable without heating the mother solution. In some embodiments, the ophthalmic device is obtainable without heating the API. In some embodiments, active pharmaceutical ingredient / s (API) are incorporated into one or more solution each of which is successively cast onto a support surface to provide a multi-layer film. In some embodiments, separately cast layers have one or more different properties (e.g. thickness, mucoadhesive, lubricious, containing active pharmaceutical ingredient / s (API)). In some embodiments, one or more surface is treated to provide it with different properties e.g. a surface is treated to become more adhesive and / or more lubricious.

[0471] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0472] Table of contents

[0473] 1. Introduction to the disclosure

[0474] 2. Exemplary forms / geo metrics 2.1 Exemplary methods of use

[0475] 2.2 Exemplary detailed method

[0476] 2.3 Exemplary ophthalmic devices

[0477] 2.4 Exemplary degradation

[0478] 2.5 Exemplary methods of treatment 2.6 Exemplary materials

[0479] 2.6.1 Exemplary lubricant material 2.6.2 Exemplary mucoadhesive material

[0480] 2.6.3 Exemplary therapeutic materials

[0481] 2.6.4 Exemplary nanoparticle and / or microparticle active pharmaceutical ingredient / s (API)

[0482] 2.7 Summary of Exemplary forms / geometries

[0483] 3. Exemplary elastomeric matrix comprising PVOH

[0484] 3.1 Exemplary elastomeric matrix

[0485] 3.2 Exemplary mechanical properties

[0486] 3.3 Exemplary plasticizers

[0487] 3.4 Exemplary compositions of elastomeric matrices

[0488] 3.5 Exemplary composite elastomeric matrix

[0489] 3.6 Exemplary Medic al / Ophthalmic device

[0490] 3.7 Exemplary method of treatment

[0491] 3.8 Exemplary method of preparation

[0492] 3.9 Summary of exemplary elastomeric matrix comprising PVOH

[0493] 4. Exemplary elastomeric matrix comprising two or more types of PVOH

[0494] 4.1 Exemplary basic composition of an exemplary elastomeric matrix

[0495] 4.2 Exemplary degrees of hydrolysis (D.H.), degrees of polymerization (D.P.), degradation time and combinations thereof

[0496] 4.3 Exemplary amounts of components within an exemplary elastomeric matrix composition

[0497] 4.4 Exemplary mechanical properties

[0498] 4.5 Exemplary plasticizers

[0499] 4.6 Exemplary composite elastomeric matrix

[0500] 4.7 Exemplary Medic al / Ophthalmic device

[0501] 4.8 Exemplary method of treatment

[0502] 4.9 Exemplary method of preparation

[0503] 5. Additional exemplary information about exemplary ophthalmic devices

[0504] 5.1 Exemplary compositions of an exemplary ophthalmic device

[0505] 5.2 Exemplary process for manufacturing an exemplary ophthalmic device

[0506] 5.3 Exemplary shape of exemplary ophthalmic device

[0507] 6. Exemplary use of the exemplary ophthalmic device in the treatment for Presbyopia

[0508] 6.1 Introduction

[0509] 6.2 Exemplary pharmaceutical active ingredients (API) for treating Presbyopia 6.3 Exemplary method of preparation of the ophthalmic device with the pharmaceutical active ingredient (API) for the treatment for Presbyopia

[0510] 6.4 Exemplary potential advantages of using the exemplary ophthalmic device for the delivery of pharmaceutical active ingredients (API)

[0511] 6.5 Exemplary general mechanism of action of the ophthalmic device in the treatment for Presbyopia

[0512] 6.6 Exemplary preliminary clinical results

[0513] 7. Exemplary use of the exemplary ophthalmic device in the treatment for Dry Eye

[0514] 7.1 Introduction

[0515] 7.2 Exemplary general mechanism of action of the ophthalmic device in the treatment for dry eye

[0516] 7.3 Exemplary potential advantages of using the exemplary ophthalmic device for the treatment for dry eyes

[0517] 7.4 Exemplary demulcent content comparison between the exemplary ophthalmic device and a typical OTC eye-drop

[0518] 1. Introduction to the disclosure

[0519] In some embodiments, the invention relates to an ophthalmic device made of an elastomeric matrix having specified compositions and forms (or geometries).

[0520] In the following chapters, exemplary embodiments of forms (geometries) will be described in chapter 2, followed by exemplary embodiments of elastomeric matrices and their compositions in chapters 3 and 4. Some exemplary ophthalmic devices shaped as described in chapter 2 and comprising elastomeric matrix composed as described in chapters 3 or 4 are described in chapter 5, but every form or geometry described in chapter 2 may be made of an elastomeric matrix composed as described in chapters 3 and 4, even if not explicitly recited in chapter 5.

[0521] Chapters 6 and 7 describe exemplary uses of ophthalmic devices described in chapters 2 through 5. Chapter 6 describes the use of such device for treating presbyopia, and chapter 7 describes the use of such device for treating dry eye disease (aka dry eye syndrome).

[0522] 2. Exemplary geometries / shapes of exemplary ophthalmic devices

[0523] In the following paragraphs exemplary geometric al / shape characteristics of an exemplary ophthalmic device will be disclosed. 2.1. Exemplary methods of use

[0524] Referring now to Figure 1 showing a method of use of an ophthalmic device, according to some embodiments of the invention. The ophthalmic device described in the chapter 2 may be composed as described in chapter 3 or 4, for example, as described in chapter 5.

[0525] At 100, in some embodiments, the ophthalmic device is positioned within an eye. For example, placed on an eye surface, for example, on the bulbar conjunctiva and / or onto a portion of the sclera.

[0526] At 102, in some embodiments, the ophthalmic device elutes medication into the eye.

[0527] At 104, in some embodiments, the ophthalmic device exits the eye. Where, in some embodiments, the device exit is manual (e.g., by the user or a caregiver) and / or the device is expelled by the eye. Where, in some embodiments, prior to exit of the ophthalmic device, the device disintegrates / degrades, at least partially. In some embodiments, exiting the eye includes one or more feature of one or more of steps 514-524 in Figure 5.

[0528] Referring now to Figure 2 showing a method of treatment using an ophthalmic device, according to some embodiment of the invention.

[0529] At 200, in some embodiments, the ophthalmic device is positioned on the bulbar conjunctiva and at least partially underneath an eyelid of the eye e.g. fully underneath the eyelid. Where, in some embodiments, a retention portion of the ophthalmic device is positioned adjacent to an opening of the eyelid and deeper into the conjunctival sac than a tarsal plate of the eyelid e.g. when the eyelid is open and closed.

[0530] At 202, in some embodiments, interaction between the retention portion, the eyelid and / or eyeball, prevents escape of the ophthalmic device from underneath the eyelid. In some embodiments, interaction between the tarsal plate of the eyelid with the slope and / or height of the device acts to retain the device within the eyelid, behind the tarsal plate. In some embodiments, interaction between the tarsal plate and the device is associated with deformation of tissue of the eyelid around the device. In some embodiments, alternatively or additionally to force of the tarsal plate, reactive force of the tissue from deformation of the eyelid acts on the device to prevent movement of the device e.g. out of the eyelid and / or deeper into the cul-de-sac of the eye. Alternatively or additionally, in some embodiments, force between the eyeball and a posterior surface of the device acts to prevent movement of the device, where, in some embodiments, the force includes reactive force of pressure of the eyelid onto the device and then to the eyeball and / or suction forces between the device and eyeball.

[0531] Referring now to Figure 3A showing a simplified schematic cross sectional view of an eye. Referring also to Figure 3B showing a simplified schematic cross sectional view of an ophthalmic device 300 in position on an eye surface, when the eye is closed, according to some embodiments of the invention.

[0532] Referring also to Figure 3C showing a simplified schematic cross sectional view of an ophthalmic device 300 in position on an eye surface, when the eye is open, according to some embodiments of the invention.

[0533] In some embodiments, cross sections of Figures 3A-C are cross sections taken in a superiorinferior direction e.g. are sagittal cross sections of the eye.

[0534] In some embodiments, device 300 is covered by a lower eyelid 346 when the eye is closed (Figure 3B) and when the eye is naturally open (Figure 3C). In some embodiments, device 300 is positioned close enough to the eyelid opening e.g. on the bulbar conjunctiva and not deep into the cul-del-sac direction that manual movement, of the eyelid (e.g. without causing the user discomfort) is sufficient to reveal the device, at least partially.

[0535] In some embodiments, device 300 is positioned on an eye surface which is a portion of a surface of conjunctiva around an eyeball 308. In some embodiments, ophthalmic device 300 resides on a bulbar conjunctiva portion of a sclera, a region of conjunctiva adjacent to the cornea and in between the fornix conjunctiva 340 and cornea 302.

[0536] In some embodiments, device 300 has a body including a posterior surface 316, and an anterior surface 318. In some embodiments, device 300 has a retention portion 336 which is, in some embodiments, a portion of device 300 adjacent to an opening 350 of eyelid 346. In some embodiments, retention portion 336 is sufficiently thick at a short distance from a leading edge 366 of device 300 and / or presents a sufficiently steep slope to eyelid 346 that device 300 is retained underneath eyelid 346, for example, by a tarsal 348 plate. In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made of a continuous material, meaning it does not comprise macroscopic gaps and / or empty areas within it. In some embodiments, a gap or empty area is defined as macroscopic if it is larger than 0.2mm. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0537] In some embodiments, retention portion 336 includes one or more feature of one or more of retention portions 636 Figures 6A-B, 736 Figure 7, 1336 Figure 13A-C, 1436 Figure 14, 1536 Figure 15A-D and / or other retention portion / s as described elsewhere in this document. In some embodiments, reactive force associated with deformation of eyelid 346 and / or conjunctiva 308 around device 300 and / or interaction between tarsal plate 348 and retention portion 336 act to hold device 300 in position on the eye surface and / or underneath eyelid 346.

[0538] Referring now to Figure 3D showing a simplified schematic top view of an ophthalmic device 300 in position on an eye surface, according to some embodiments of the invention.

[0539] In some embodiments, as shown for example in Figure 3D, the ophthalmic device 300 is positioned on an eye surface (e.g. a sclera), for example, on an inferior portion of the bulbar conjunctiva underneath the lower eyelid 346 e.g. entirely underneath the lower eyelid 346.

[0540] Referring now to Figure 4A showing a simplified schematic top view of an ophthalmic device 400 in position on an eye surface 404, according to some embodiments of the invention.

[0541] In some embodiments, as shown for example in Figure 4A, the ophthalmic device 400 is positioned an eye surface 404 (e.g. a sclera), for example, on a superior portion of the bulbar conjunctiva underneath the upper eyelid 444 e.g. entirely underneath the upper eyelid 444. In some embodiments, when device 400 is positioned on a superior portion of the eye, positioning is deeper within the fornix (e.g. in comparison to position where the device is positioned on an inferior portion of the eye e.g. underneath the lower eyelid).

[0542] Referring now to Figure 4B showing a simplified schematic cross sectional view of an ophthalmic device 400 in position on an eye surface 404, when the eye is closed, according to some embodiments of the invention.

[0543] Where, in some embodiments, eye surface 404 is a superior portion of the sclera. Where, in some embodiments, device is held underneath upper eyelid 344, for example, when the eye is open and closed.

[0544] In some embodiments, a depth to which device 400 is inserted and / or a length of the device extending underneath the upper eyelid is deeper than that of a device for use under the inferior eyelid. In some embodiments, increasing likelihood of the device remaining underneath the superior eyelid where, generally, the eyelid and tarsal plate have larger extent.

[0545] In some embodiments, reactive force associated with deformation of eyelid 444 and / or conjunctiva 408 around device 400 and / or interaction between superior tarsal plate 462 and retention portion 436 act to hold device 400 in position on the eye surface and / or underneath upper eyelid 444.

[0546] Referring now to both Figure 3D and Figure 4A, arrows 360, 460 illustrate ranges of exemplary positions for device / s 300, 400 e.g. with respect to visible portions of an eye. Where, in some embodiments, ophthalmic device 300 is positioned underneath a central portion of lower eyelid 346. Where, in some embodiments, ophthalmic device 400 is positioned underneath a central portion of upper eyelid 444.

[0547] For example, a central 2- 10mm, or 2-7mm, e.g. as measured along a contour of a junction between the eyelid and an eye surface (e.g. sclera 304, 404).

[0548] For example, at least 1mm, or 2mm, or 5mm, from the inner and / or outer eye corners e.g. as measured along a contour of a junction between the eyelid and the eye surface (sclera 304, 404 and / or cornea 302, 402).

[0549] For example, a central 30-80%, or 40-70%. Where, in some embodiments, the portion is measured as a length along a contour of the eyelid (e.g. at a junction between the eyelid and the eye surface) with respect to a total length measured along the contour of the eyelid between corners of the eye, when the eye is closed and / or open.

[0550] In some embodiments, device / s 300, 400 are symmetrical in shape, e.g. in one or more dimension. In some embodiments, device / s 300, 400 have a circular footprint e.g. when residing on an eye surface (e.g. sclera 304, 404).

[0551] 2.2. Exemplary detailed method

[0552] Referring now to Figure 5 showing a method of use of an ophthalmic device, according to some embodiments of the invention.

[0553] At 500, in some embodiments, optionally, a substance is applied to an eye and / or to the ophthalmic device.

[0554] For example, in some embodiments, the device is stored in a dry or partially hydrated form and is hydrated before use (e.g. insertion into the eye). For example, by applying water and / or a hydrating solution to the device prior to positioning the device on an eye surface. In some embodiments, the device is soaked in a hydrating solution before applying to the eye e.g. for 5 seconds - 20 mins. In some embodiments, the device is humidified by exposing to humid air and / or gas before applying to the eye e.g. for 1 minute - 2 hours.

[0555] In some embodiments, one or more therapeutic material is applied to the device. In some embodiments, mucoadhesive material and / or lubricious material is applied to the device e.g. one or more portions of the device.

[0556] At 502, in some embodiments, the ophthalmic device is applied to an eye surface. In some embodiments, applying includes bringing the device into contact with the eye surface e.g. the sclera e.g. bulbar conjunctiva. In some embodiments, applying includes retracting the eyelid under which the device is to be positioned and placing the device on an eye surface usually underneath the eyelid.

[0557] In some embodiments, the device is directly and / or manually applied to the eye surface. For example, by the patient themselves. In some embodiments, a caregiver applies the device. Optionally, in some embodiments, the device is applied using an applicator.

[0558] In some embodiments, for example, when the device is not rotationally symmetrical, the device is orientated prior to and / or during positioning on the eye surface. In some embodiments, an applicator is sized and / or shaped and / or has one or more indicator to aid positioning the device at a desired orientation within the eye. Orientations, for example, as described elsewhere in this document e.g. orientation with respect to a leading edge and / or shape (e.g. elongation) of the device.

[0559] At 504, optionally, in some embodiments, after application to the eye surface, the ophthalmic device is repositioned. For example, by manipulation of the eye and / or ophthalmic device and / or eyelid. For example, in some embodiments, the ophthalmic device is positioned protruding at least partially from underneath an eyelid and, in some embodiments, the ophthalmic device is repositioned (e.g. to be fully underneath the eyelid) by directly moving the ophthalmic device and / or by manipulating the eye (e.g. eyelid) to move the ophthalmic device. For example, in some embodiments, the ophthalmic device is placed on the sclera above the eyelid and then is manipulated in an inferior direction e.g. until it is covered by the eyelid and / or held in position by the tarsal plate. In some embodiments, suction forces between the device and the eye surface (e.g. the posterior surface of the device) are sufficiently low, at least initially, to enable repositioning of the device. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0560] At 506, in some embodiments, the ophthalmic device is held in place by eye anatomy when the device is worn, and the eye is rolled. For example, held underneath the eyelid e.g. by interaction between the tarsal plate and a retention portion of the device e.g. including one or more feature as illustrated in and / or described regarding device 300, tarsal plate 348 Figures 3B-C and / or device 400, tarsal plate 462 Figure 4B.

[0561] At 508, in some embodiments, optionally, the device hydrates within the eye, for example, absorbing tear fluid.

[0562] At 510, optionally, in some embodiments, the ophthalmic device adheres to the eye surface. Where, in some embodiments, adherence is associated with pressure between the ophthalmic device and the eye surface (e.g. posterior surface of the device). In some embodiments, curvature of the ophthalmic device posterior surface aids adherence of the device to the eye surface. In some embodiments, this adherence is amplified by pressure of the eyelid onto the device. In some embodiments, one or more sharp edge of the device aids adherence of the device to the eye surface. In some embodiments, one or more concavity and / or protrusion e.g. on a posterior surface of the device aids adhesion.

[0563] In some embodiments, when the device is applied to the eye surface (i.e. is in situ), material properties of a mucoadhesive layer of the device upon application and / or after the mucoadhesive layer properties change in situ (e.g. hydrate) adhere the device to the eye surface.

[0564] In an exemplary embodiment, adhesion of the ophthalmic device to the eye surface is sufficient to maintain the device on the eye surface (e.g. sclera) in event of escape of the device from underneath the eyelid. For example, for a short period of time for example, less than 10 minutes, for example, 1 minute - 1 hour, for example, during blinking e.g. during a few blinks e.g. 1-10 blinks, or 1-100 blinks. In which time, in some embodiments, a user returns the device to underneath the eyelid e.g. according to one or more feature as described regarding step 504.

[0565] At 512, in some embodiments, the device remains on the eyeball for a time period. For example, remaining underneath the eyelid.

[0566] In some embodiments, the device is maintained in situ (in the eye) for a period of at least 1 minute, or for 1-10 minutes, or for at least 0.5 hours, or for 0.1 - 2 hours, or for 2-8 hours, or for over 8 hours, or for 8-24 hours, or 1-7 days, or 7 days - 1 month, or 1-3 months, or 3 months -1 year, or 1-30 days, or 1 month-1 year.

[0567] In some embodiments, the device remains and / or is maintained in situ (residence time) and is expelled and / or removed from the eye after less than about 24 hours from administration. Where expelling and / or removal, in some embodiments, leaves the eye clean from the device (e.g. without leaving behind debris), for example, the eye being ready for an additional administration e.g. of an additional device.

[0568] At 514, optionally, in some embodiments, one or more portions of the device degrades and / or disintegrates.

[0569] In some embodiments, degradation of the device occurs by one or more of mechanical degradation (such as eyeball or eyelid movement), chemical degradation (such as tear fluid) or biological degradation (such as enzymatic activity).

[0570] In some embodiments, speed of degradation is increased by a user, for example, where, in some embodiments, pressure is applied to the device (e.g. manually) to break the device into more than one part and / or hasten such breakage. In some embodiments, upon breaking into more than one part, one or more of the parts are sized and / or shaped (e.g. having retention portion / s) to remain underneath the eyelid.

[0571] In some embodiments, the device includes portions which degrade at different rates. For example, including one or more features as illustrated in and / or described regarding Figure 28 and / or Figure 29 and / or Figures 30A-B.

[0572] At 516, in some embodiments, the device performs treatment, for example, eluting medication into the eye. In some embodiments, elution is associated with degradation of eluting portion / s of the device.

[0573] At 518, optionally, in some embodiments, one or more portions of the device disintegrates. For example, a portion of the device disintegrating to reveal therapeutic material and / or to reveal additional therapeutic material. In some embodiments, portion / s of the device associated with device adhesion disintegrate. For example, a mucoadhesive layer. For example, portions which contribute to mechanical adhesion e.g. portion / s of a device edge and / or portion / s to change curvature of one or more surface of the device.

[0574] At 520, optionally, in some embodiments, the device disintegrates. For example, where disintegration of the device mechanically reduces adhesion of the device to the eye and / or reduces size of the device and / or breaks the device into pieces. In some embodiments, the entire device degrades after residence on the eye surface for a time period of between about 0.1 hours to 1 year, or less than 0.1 hours (e.g. immediately e.g. within a minute after placement on the eye).

[0575] At 522, in some embodiments, the device ophthalmic and / or portion / s of the ophthalmic device expelled from the eye naturally e.g. expelled by movement of the eyelid and / or eyeball and / or by blinking and / or tearing. In some embodiments, the device is expelled using manipulation of the eyelids. In some embodiments, portions of the device are expelled (e.g. when step 520 has occurred). In some embodiments, the device e.g. where the device remains in one portion, is expelled naturally. For example, upon degradation of adhesive related portion / s of the device.

[0576] At 524, optionally, in some embodiments, the ophthalmic device and / or portion / s of the device are removed e.g. manually. For example, by application of mechanical force e.g. pinching and / or applying suction and / or during use of a removal device (e.g. suction cup, tweezers) and / or by flushing of the eye.

[0577] In some embodiments, the ophthalmic device is removed by a combination of manual and natural processes. For example, in some embodiments, pressure is applied to the device to break it into more than one piece or to hasten such breakage. Where, in some embodiments, one or more of the pieces are then expelled naturally and / or dissolved. In some embodiments, concurrent to one or more step and / or in between steps of the method described steps 500-524, one or more additional treatment method is administered concomitantly, sequentially or simultaneously. For example, in some embodiments, topical medication is applied e.g. during residence time of the device on the eye surface.

[0578] 2.3. Exemplary ophthalmic devices

[0579] Referring now to Figure 6A showing a simplified schematic top view of an ophthalmic device 600 in position on an eye surface 604 underneath an eyelid 646, according to some embodiments of the invention.

[0580] In some embodiments, device 600 includes a retention portion 636 which is formed, when the device is in position on an eye surface, by a portion of device 600 adjacent to an opening of eyelid 646 (where, in some embodiments, eyelid 646 is a lower eyelid).

[0581] In some embodiments, retention portion 636 is a portion of device 600 extending from a leading edge 666 of the device inwards (e.g. towards a center of device 600).

[0582] In some embodiments, retention portion 636 extends inwards from leading edge 666 by at least a portion 630 of a depth 620 of device 600. In some embodiments, retention portion 636 extends laterally e.g. along leading edge 666 by at least a portion of a lateral length 622 of device 600.

[0583] Referring now to Figure 6B showing a simplified schematic cross section of an ophthalmic device 600, according to some embodiments of the invention.

[0584] Figure 6B illustrates a cross section of device 600 of Figure 6A where the cross section is taken along line BB of Figure 6A. Figure 6B illustrates a range of cross sections of device 600 parallel to line BB of Figure 6A e.g. for all of lateral extent 628 of retention portion 636. Figure 6B illustrates each of a range of cross sections of device 600 of Figure 6A where the cross sections are along line BB of Figure 6A or parallel to line BB of Figure 6A.

[0585] In some embodiments, the body of the ophthalmic device 600 is symmetrical relative to its longitudinal axis (schematically shown by line AA) and relative to its transversal axis (schematically shown by line BB). For example, when looking at the ophthalmic device 600 (or other ophthalmic devices for example 300, 400, 800, 900, 1300, 1400, 1500, 1600, 1700, 1900, 2000, 2500, 2600, 2700, 2900, 3000, 3100) from the anterior surface, the device is symmetrical relative to its longitudinal axis (AA) and relative to its transversal axis (BB). In some embodiments device 600 has an anterior surface 618 and a posterior surface 616. In some embodiments, device 600 is a volume between the surfaces 616, 618, e.g. one or both of the surfaces curving to meet the other surface. For example, as illustrated in Figure 6B where anterior surface 618 curves to meet posterior surface 616. In some embodiments, when resident on an eye surface, posterior surface 616 is adjacent to the eye surface (e.g. a sclera). In some embodiments, when resident on an eye surface, anterior surface 618 is adjacent conjunctiva of an eyelid (e.g. of a lower eyelid). In some embodiments, anterior surface 618 is convex and / or has a convex portion. In some embodiments, posterior surface 616 is convex and / or has a convex portion, as schematically shown by dotted line 616a in Figure 6B. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0586] In some embodiments, retention portion 636 has a holding height 662 at a holding distance 664 from leading edge 666. Where, in some embodiments, the holding height 662 is maintained (or exceeded) for a length 632 extending from leading edge towards trailing edge 634.

[0587] In some embodiments, retention portion 636 has concave and / or sufficiently steep slope 614 (e.g. as defined by slope of anterior surface 618) from leading edge 666 towards holding height 662. Where, in some embodiments, at a first distance 652 from leading edge 666, device 600 has a first height 654 and / or at a second distance 656 from leading edge 666, device 600 has a second height 658. In some embodiments, second distance 656 is at most 1mm and first distance 652 is at least 1mm.

[0588] Where distances from leading edge 666 are measured along anterior surface and / or from the leading edge along a surface as described regarding measurements of heights (e.g. elsewhere in this document).

[0589] In some embodiments, an angle 0 of a slope of anterior surface 618 at leading edge 666 (e.g. of a tangent to the surface at the leading edge) or at an edge of the retention portion, is at least 35°, or at least 46°, or is 46-90°, or is 46-86°, or is 46-70°, or is lower or higher or intermediate angles or ranges. Where, in some embodiments, the angle is measured with respect to a planar surface on which the device is resting in a relaxed configuration. Where, in some embodiments, the angle is measured with respect to an eye surface, for example, an angle of the eye surface at the leading edge 666 and / or at an edge of the retention portion.

[0590] In some embodiments, anterior surface 618 has a radius of curvature 624 extending from leading edge 666 to holding height 662. Where, in some embodiments, radius of curvature 624 is equal to a peak height of the device e.g. as measured between posterior 616 and anterior 618 surfaces of device 600. In some embodiments, e.g. as illustrated in Figure 6B the device cross section (for one or more cross section) is symmetrical, e.g., has mirror symmetry. In some embodiments, the device is symmetrical in at least one direction, for example, about line BB and / or line AA as illustrated in Figure 6A.

[0591] In some embodiments, ophthalmic device 600 is elongate. Where, in some embodiments, a length 622 of device 600 is larger than a width 620 of device 600. In some embodiments length 622 is 1.5-10 times.

[0592] A potential advantage of an elongate device is that long sides 666, 634 of the device provide an increased surface for interaction with the eyelid / s e.g. for retention of the device within the eyelid and / or when removing the device using pinch removal.

[0593] In some embodiments, device 600 is positioned underneath eyelid 646 where a direction of elongation of device 600 is along a direction of an eyelid contour e.g. a contour of the opening to eyelid 646 and / or along a contour of a tarsal plate 648 of eyelid 646. A potential advantage of elongation of device 600, is an increased length of interaction of the device and the eyelid e.g. the tarsal plate (e.g. in comparison to the length of interaction of a device of the same volume and / or footprint size but less elongated). A potential advantage of elongation of the device, in some embodiments, is reduced likelihood of rotation of the device when in situ. In some embodiments, length 622 is larger than a depth of a cul-de-sac of the eye e.g. potentially preventing device 600 from rotating so that a direction of elongation is aligned in a direction extending from the eyelid opening to the bottom of the cul-de-sac.

[0594] In some embodiments, width 620 and / or length 622 of device 600 is 2- 10mm. For example, in some embodiments, length 622 is 5- 10mm and / or width 620 is 3-5mm and / or height 662 and / or height 624 is 2-2.5mm.In some embodiments, holding height 662 is at least 2mm at a distance 664 from leading edge 666 of 2mm. Alternatively or additionally, in so some embodiments, at distance 652 of 0.5mm height 654 is at least 1.3mm. Alternatively or additionally, in some embodiments, at distance 656 of 1mm height 658 is at least 1.7mm.

[0595] In some embodiments, where distance 664 is 2mm, height 662 is larger than 0.5-5mm, or 0.5-2mm, or l-2mm, or lower or intermediate or higher heights or ranges.

[0596] In some embodiments, holding height 662 is maintained for a region of the cross section e.g. length 632 being at least 1mm.

[0597] In some embodiments, peak height 624 is at most 5mm, or 4mm, or about 3mm or about 2mm.

[0598] In some embodiments, for example, as described elsewhere in this document, anterior surface 616 is curved, e.g. concave. For example, including one or more feature of one or more of device 1300 Figures 13A-C, device 1400 Figure 14 and / or other device / s elsewhere in this document.

[0599] In some embodiments, device 600 is sufficiently rigid and / or resistance to forces (e.g. suction forces) when on an eye that the device does not deform significantly when in an eye so that, in some embodiments, heights as described above are heights above a one or more of:

[0600] - a plane on which the relaxed device rests,

[0601] - a plane connecting circumferential edges of the device or a majority (e.g. at least 80%, or at least 90%, or at least 95%, or at least 99%) of a circumference of the device,

[0602] - a curved surface on which the relaxed device rests e.g. a surface with curvature in one or more directions of an eyeball, e.g. a sphere with radius of curvature of the eyeball.

[0603] In some embodiments, distances measured from leading edge 666 are measured along the plane used for measurement of height and / or along the posterior surface and / or along the anterior surface and / or a plane equidistant between the surfaces.

[0604] In some embodiments, heights e.g. as described regarding one or more of 654, 658, 662, 624 are heights of the device in situ above an eye surface. Where, in some embodiments, anterior surface 616 is curved (e.g. concave or convex). In some embodiments, forces (e.g. suction between the device and eyeball and / or pressure of the eyelid onto the device via the anterior surface) on the device act to flatten the device when the device is in situ on the eye surface.

[0605] Alternatively, the heights described are for a relaxed device, where, in some embodiments, flattening of the device reduces one or more height of the device by at most 30%, or at most 5- 50%, or at most 5-30%, or at most 5-20%, from their original height / s. For example, height reducing by at most 30% corresponding to, in some embodiments, upon flattening the maximum height being at least 70% of an original (prior to flattening) maximum height.

[0606] Referring now to Figure 7 showing a simplified schematic illustrating cross sections of portions of devices, according to some embodiments of the invention.

[0607] Figure 7 illustrates exemplary anterior surfaces 714, 714b, 714c of exemplary devices. Where, each of the device anterior surface contours, has a holding thickness 762 at a holding distance 764 from a leading edge 766 of the device. Convex anterior surface 714 (e.g. as described regarding anterior surface 618 of device 600 Figure 6B) is illustrated for comparison purposes to, for example, an embodiment, where contour 714c extending from leading edge 766 to holding thickness 762 has a constant slope (e.g. within 10% of constant) and an embodiment where contour 714b is concave.

[0608] Referring now to Figures 8-12 showing simplified schematic top views of devices 800, 900, 1000, 1100, 1200, according to some embodiments of the invention. Dashed lines are contour lines of an anterior surface of the device indicating, for the anterior surface, same distances above a height defined by a plane of footprints of the device as indicated in Figures 8-12 by solid lines.

[0609] In some embodiments, as shown for example in Figure 8, device 800 has the same slope and / or edge contour extending around a perimeter (or extending around at least 50%, or 70%, or 90%) of the device (e.g. as indicated by contour lines).

[0610] Where, for example, a slope 814 of the anterior surface adjacent to a leading edge 866 and a slope 874 adjacent to a trailing edge 834 are the same. In some embodiments, slopes 876, 878 on lateral sides of the device are the same e.g. the same as each other and / or the same as slope / s 814, 874. A potential benefit being that holding forces on the device (e.g. of the eyelid on the device) of the device are maintained (or changed less) upon rotation of the device (e.g. while the device is in position e.g. underneath an eyelid). In some embodiments, slopes 876, 878, of lateral sides of device 800 are different, for example, to configure device 800 to changing eye anatomy e.g. in a direction along a contour of an eyelid.

[0611] In some embodiments, as shown for example in Figure 9 and Figure 11, different edges of the device have different slopes. For example, in some embodiments, a slope 914, 1114 of a retention portion is located in a central region of device 900, 1100 leading edge 966, 1166 where, in some embodiments, one or both of lateral edges of the device have lower gradient slopes 976, 978, 1176, 1178.

[0612] In some embodiments, as shown for example in Figure 10, a slope 1074 of the anterior surface of the device extending to a trailing edge 1034 is higher than that of a retention portion slope 1014 adjacent to a leading edge 1066 of device 1000.

[0613] In some embodiments, as shown for example in Figure 11 and Figure 12, a region of the device adjacent to a leading edge 1166, 1266 hosts the retention portion and a slope of the device 1174, 1274 extending towards a trailing edge has lower gradient slope. A potential benefit being increased comfort as the device tapers in thickness as it extends further underneath the eyelid towards the apex of the conjunctival fornix. In some embodiments, one or both lateral sides of the device also have lower gradient slope 1176, 1178 than retention portion slope 1114.

[0614] Referring now to Figure 13 A showing a simplified schematic view of an ophthalmic device 1300, according to some embodiments of the invention. Figure 13 A shows an isometric view of ophthalmic device 1300. In some embodiments, the form of the ophthalmic device 1300 is a domelike form or half a sphere. Also referring to Figure 13B showing a simplified schematic cross sectional view of an ophthalmic device 1300, according to some embodiments of the invention. And also referring to Figure 13C showing a simplified schematic top view of an ophthalmic device 1300, according to some embodiments of the invention.

[0615] In some embodiments, ophthalmic device 1300 has an anterior surface 1316 and a posterior surface 1318. Where, in some embodiments, anterior surface 1318 curves to meet posterior surface 1316 at an edge 1366 of device 1300.

[0616] In some embodiments, ophthalmic device 1300 is symmetric, for example about one or more axis of symmetry. In some embodiments, as shown for example in Figure 13C, ophthalmic device 1300 is symmetric about line AA and / or line BB.

[0617] In some embodiments, device 1300 has rotational symmetry, for example about a central axis 1370 which extends through a center 1372 of device top view. Where axis 1370 is perpendicular to one or both of anterior 1318 and posterior 1316 surfaces.

[0618] In some embodiments, device 1300 footprint (e.g. as illustrated in Figure 13C) has a diameter of 2-10mm, or 3-8mm, or 4-7mm, or 5-6mm. Where, in some embodiments, device 1300 has a height of 2-2.5 mm.

[0619] In some embodiments, posterior surface 1316 is curved, for example, in one or more directions. For example, in some embodiments, Figure 13B illustrates a cross section taken of device along line AA and / or line BB of Figure 13C.

[0620] A potential benefit of a symmetrical (e.g. rotationally symmetrical device) is that device characteristics e.g. regarding eye anatomy, are maintained if the device rotates in situ.

[0621] In some embodiments, not shown in Figures 13A, 13B or 13C, anterior surface 1318, has higher radius of curvature (RA - Radius Anterior) than a radius of curvature of posterior surface 1316 (RP - Radius Posterior). For example, where, in some embodiments, RA is 1.2-10 or 1.2-5 times RP.

[0622] In an exemplary embodiment, a radius of curvature of anterior surface 1318 is equal (or about equal, for example, within 20%, or within 10%, or within 5%) of a maximum thickness 1324 of device 1300. For example device 1300 anterior surface 1318 having a hemisphere shape.

[0623] In an exemplary embodiment, a radius (e.g. half of width 1320) of the device footprint (Figure 13C) and / or edges 1366 is 0.5-10mm, or l-10mm, or l-5mm, or 2-4mm, or 2.5-3mm.

[0624] Hemisphere- shaped devices e.g. as described regarding Figures 13A-C, and having diameter 1320 of 5.5mm, having a concave posterior surface 1316 and having height 1324a (as measured when the device is in a relaxed configuration on a planar surface) 2mm were placed on the sclera under the lower eyelid of human volunteers and stayed there comfortably for several hours. Elongated-Hemisphere-shaped devices or also defined as having an elongated elliptical half-sphere form e.g. as described regarding Figures 15A-D, having a concave posterior surface and having length 1522 of 6 mm, width 1520 of 4 mm, and height 1524 of 2 mm were placed on the sclera under the lower eyelid of human volunteer’s eyes and stayed there comfortably for several hours.

[0625] Figure 14 is a simplified schematic cross sectional view of an ophthalmic device 1400, according to some embodiments of the invention.

[0626] In some embodiments, curvature and / or slope of a surface 1418 of device 1400 changes along a cross section of the device. For example, in some embodiments, curvature of anterior surface 1418 changes moving from a leading edge 1466 towards a trailing edge 1434. Where leading edge 1466 and / or trailing edge 1434 include one or more feature as described regarding leading edge 666 and / or trailing edge 634 Figure 6A, Figure 6B respectively. For example, device 1400 having a retention portion 1436 with a slope 1414 and / or having a holding thickness 1424 where a curvature of anterior surface 1418 then reduces (e.g. from a maximal thickness portion of the device) towards trailing edge. Where, in some embodiments, slope 1414 and / or holding thickness 1424 have one or more feature of slope 614 and / or thickness 624 Figure 6 A and / or Figure 6B. In some embodiments, such a cross section positions the retention portion non-centrally with respect to the top view and / or footprint of the device e.g. off center and towards a side of the device proximal to an opening of the eyelid when the device is in situ.

[0627] In some embodiments, (e.g. where anterior surface 1418 has changing curvature) posterior surface 1416 has constant curvature 1416. Alternatively, in some embodiments, posterior surface curvature 1416 also changes moving across one or more cross section of the device. For example, thinning of the device in a direction moving away from the leading edge, in some embodiments, being due to decrease in curvature of anterior surface combined with increase in curvature of the posterior surface. In some embodiments, (e.g. where anterior surface 1418 has constant curvature) thinning of the device in a direction moving away from the leading edge is due to increase in curvature of the posterior surface.

[0628] Referring now to Figure 15A showing a simplified schematic top view of an ophthalmic device 1500, according to some embodiments of the invention. Also referring to Figure 15B showing a simplified schematic view of an ophthalmic device 1500, according to some embodiments of the invention. Figure 15B shows an isometric view of ophthalmic device 1500. And also referring to Figure 15C showing a simplified schematic cross sectional view of an ophthalmic device, according to some embodiments of the invention. Eastly, also referring to Figure 15D showing a simplified schematic cross sectional view of an ophthalmic device 1500, according to some embodiments of the invention.

[0629] In some embodiments, device 1500 is elongate. In some embodiments, device 1500 is defined as having an elongated-Hemisphere- shaped form or also defined as having an elongated elliptical half-sphere form. Where, in some embodiments, elongation of device 1500 includes one or more feature as described regarding device 600 Figure 6A. In an exemplary embodiment, a device width 1520 is 1.1-10 times, or 1.1-5 times, or 1.2-3 times, or 1.2-2.5 times, or about 1.5-2 times a device length 1522.

[0630] In some embodiments, a leading edge 1566 of device 1500 is straight and / or a trailing edge 1534 is straight. In some embodiments, leading edge 1566 and trailing edge 1534 are parallel (or within 1, or 3, or 5, or 10 degrees of parallel). In some embodiments, leading edge 1566 and / or trailing edge 1534 are straight where compared to, for example, lateral edges 1580 and 1582. In other words, leading edge 1566 and / or trailing edge 1534 may comprise straight portions, whereas lateral edges 1580 and 1582 are curved, and therefore do not comprise straight portions.

[0631] In some embodiments, one or both of lateral edges 1580 and 1582 are curved. A potential benefit being increased comfort for a user wearing the device. In some embodiments, one or both of edges 1580 has a radius of curvature 1584. In an exemplary embodiment, radius of curvature 1584 is half (or about half) of a device footprint width 1520.

[0632] Figure 15C illustrates a cross section of device 1500 taken laterally across the device e.g. along a direction of elongation e.g. along line CC (in Figure 15A). In some embodiments, device cross section has a radius of curvature 1588 of an anterior surface 1518 extending from a first lateral edge 1580. In some embodiments, the cross section has the same radius of curvature 1588 for anterior surface 1518 extending from second lateral edge 1582 to a central region and / or a maximal thickness 1524 of the cross section. In some embodiments, a radius of curvature 1518 of the posterior surface, in one or more directions, is l-15mm, or l-10mm, and / or has a ratio to that of the sclera being 0.1-2, or 0.5-1.

[0633] Figure 15D illustrates a cross section of device 1500 taken in a direction of leading edge 1566 towards trailing edge 1534 e.g. along line DD (in Figure 15A). In some embodiments, Figure 15D illustrates cross sections of device 1500 extending along a central region 1590 of device 1500 e.g. as illustrated by arrow 1586. In some embodiments, the cross section of Figure 15D includes one or more feature of the cross section of Figure 6B. In some embodiments, a radius of curvature 1590 of anterior surface 1518 is the same as a maximal thickness 1590 of the cross section. In some embodiments, the form of the ophthalmic device 1500 is a dome-like form or a half sphere. In some embodiments, one or more of radii of curvature 1584, 1588, 1590 are related. In some embodiments, one or more of radii of curvature 1584, 1588, 1590 with respect to one or more of each other, are the same, or are about the same, or are within 5%, or 10%, or 20%, or 30%, of each other.

[0634] In some embodiments, lateral sides of device 1500 have the same curvature towards lateral edges 1580, 1582, in directions extending from a central region 1590 of device 1500, in some embodiments, lateral edge portions of device anterior surface having a quarter hemisphere shape.

[0635] Figure 15C also illustrates (e.g. alternatively to Figure 15D) a cross section of device 1500 taken along line DD (in Figure 15A), the device, in some embodiments, having a planar central region of the anterior surface as defined by a base region 1502 of anterior surface 1518 in Figure 15C.

[0636] In some embodiments, device 1500 has a maximal thickness, extending along a lateral central line CC of device 1500 footprint (Figure 15A). In some embodiments, the maximal thickness extends along a central contour e.g. as illustrated by arrow 1586.

[0637] In an exemplary embodiment, width 1520 is 4.5mm and length 1522 is 10mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2.25mm.

[0638] In an exemplary embodiment, width 1520 is about 5mm and length 1522 is about 6.5mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2.25mm.

[0639] In an exemplary embodiment, width 1520 is about 4.5mm and length 1522 is about 8.5mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2.25mm.

[0640] In an exemplary embodiment, width 1520 is about 5.5mm and length 1522 is about 10mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2.75mm.

[0641] In an exemplary embodiment, width 1520 is about 4mm and length 1522 is about 6mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2mm.

[0642] In an exemplary embodiment, width 1520 is about 5.5mm and length 1522 is about 8.5mm. Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2.25mm.

[0643] In an exemplary embodiment, width 1520 is about 4.5mm and length 1522 is about 6.5mm.

[0644] Where, in some embodiments, thickness 1524 and / or one or more of radii of curvatures 1584, 1588, 1590 are about 2mm. Where, in some embodiments, a weight of the device is 18 mg. In some embodiments, the minimum weight of the device is 8 mg.

[0645] Referring now to both Figure 15C and Figure 15D, posterior surface 1516 is curved, at least for a portion of the posterior surface 1516, in at least one direction. For example, as illustrated by dashed lines in Figure 15C and Figure 15D which illustrate alternative posterior surface / s. In some embodiments, the posterior surface of device 1500 is concave, in at least one direction.

[0646] A potential advantage of a concave posterior surface is increased adhesion of the device to an eye surface on which the device rests. In some embodiments, not shown in Figures 15A-D, portion / s of an anterior surface 1518, have higher radius of curvature RA than the posterior surface RP. For example, where, in some embodiments, RA is 1.2-10 times RP, or 1.2-5 times RP. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0647] Referring now to a cross section taken along line DD. In an exemplary embodiment, at 0.5mm from leading edge 1566, height (and / or thickness) of the device is 1.32mm, and at a distance of 1mm from leading edge 1566, height (and / or thickness) of the device is 1.73mm, and at a distance of 2mm from leading edge 1566 height (and / or thickness) of the device is 2mm. For example, in some embodiments, a radius of curvature 1588 and / or 1590 is 2mm.

[0648] Referring now to Figures 16-20 showing simplified schematic top views of devices 1600, 1700, 1800, 1900, 2000, according to some embodiments of the invention.

[0649] In some embodiments, as shown for example in Figure 16, device 1600 is truncated at one or more side. In some embodiments, device 1600 has a curved edge 1666 and a low curvature edge 1634 (e.g. where, in some embodiments, low curvature edge 1634 is straight). In some embodiments, a region of a low curvature edge 1634 has a high curvature in a direction perpendicular to a plane of the footprint (and / or of Figure 16). For example, in some embodiments, edge 1634 hosting a retention portion e.g. having feature / s as described regarding retention portions elsewhere in this document (e.g. retention portion 636 Figure 6B).

[0650] In some embodiments, as shown for example in Figure 17, device 1700 has a top view shape which is tapered in one or more directions. For example, where, a maximum width 1730 of the device tapers towards one or more edge 1766, 1734 of device, for example, tapering more towards a first edge 1734 than towards a second edge 1766. In some embodiments, maximum width 1730 is located closer to one edge than the other e.g. towards the less tapered side of the device between maximum width 1730 and edge 1766. In some embodiments, second edge 1766 is a device leading edge and first edge 1734 is a trailing edge, leading and trailing edges including feature / s as described elsewhere in this document.

[0651] In some embodiments, as shown for example in Figure 18, an ophthalmic device 1800 has a shape having a narrow portion 1848 and / or indentation in the external form.

[0652] In some embodiments, device 1800 shape facilitates removal e.g. by pinching (e.g. manually and / or using a removal implement). Where, for example, in some embodiments, a portion configured to fold which is optionally in a central region (in one or more dimension) of the device (e.g. fold region; 1848 Figure 18) is thinner and / or has a smaller footprint extent, e.g. facilitating folding after applying pinching force at one or both of larger extent regions on either side of the smaller footprint portion. In some embodiments, device 1800 includes two retention portions, for example, one at each side of fold region 1848.

[0653] In some embodiments, as shown for example in Figure 19, a device shape 1900 e.g. device footprint is selected for anatomical fit. For example, in some embodiments, device 1900 is shaped to position the device in contact with a portion of patient anatomy. For example, in some embodiments, an elongated device is curved and / or describes a curved shape. In some embodiments, ophthalmic device 1900 includes a curved shape top view and / or footprint. In some embodiments, a central longitudinal axis 1930 of the curved shape is l-40mm long, or 5-20mm, long. In some embodiments, a radius of curvature of device 1900 is selected for the device to follow a curvature of an eyelid and / or portion of a cul-de-sac of an eyelid. Where, in some embodiments, a radius of curvature of 1928 is 20- 100mm, or 20-50mm,.

[0654] In some embodiments, the curve of device 1900 is sized and / or shaped to fit the eye e.g. a curve of an eyeball underneath an eyelid. In some embodiments, a retention portion is hosted adjacent to edge 1966. Alternatively or additionally, in some embodiments, a retention portion is hosted adjacent to edge 1934.

[0655] In some embodiments, as shown for example in Figure 20, device 2000 has one or more corners e.g. three corners for device 2000, for example, connected by sides. In some embodiments, corners of device 2000 facilitate removal of the device by pinching, for example providing the same potential distance (e.g. associated with extent) over which to apply pinch force (e.g. as a circular footprint device) but with reduced device footprint area. In some embodiments, a retention portion is hosted in a central region of device 2000 footprint. In some embodiments, retention portion / s are hosted adjacent to one or more edge of the multi-edged device.

[0656] Referring now to Figures 21-24 showing simplified schematic cross sections of devices 2100, 2200, 2300, 2400 according to some embodiments of the invention. In some embodiments, as shown for example in Figure 21, a posterior surface 2118 of device 1300 includes one or more concavity 2138.

[0657] In some embodiments, as shown for example in Figure 22, device 2200 includes both a curved posterior surface 2216 surface and one or more concavity 2238 on posterior surface 2218.

[0658] In some embodiments, as shown for example in Figure 23, device 2300 includes a concavity 2338 located on a posterior surface 2316. In some embodiments, concavity 2338 is located at a region of a retention portion 2336. For example, the concavity being adjacent to a leading edge 2366 of device, for example, within l-5mm of leading edge 2366. For example, located on a same portion (e.g. half) of the device as the retention portion 2336. Optionally, in some embodiments, curvature of an anterior surface 2318 reduces in a direction moving from a maximum thickness 2330 of device 2300 towards a trailing edge 2334 of the device.

[0659] In some embodiments, as shown for example in Figure 24, device 2400 has a highly concave posterior surface 2416, when compared for example, with the device 2300 shown in Figure 23. In some embodiments, curvature of posterior surface 2416 changes along a length of the surface e.g. from first edge 2466 (which, in some embodiments is a leading edge) to second edge 2434 (which, in some embodiments, is a trailing edge). Posterior surface 2416, in some embodiments, having a higher curvature at a region adjacent to first edge 2466. In some embodiments, height (or thickness of the retention portion e.g. as defined within the overview section and / or with respect to Figures 6A-B) is measured between the dashed line illustrated in Figure 24 and anterior surface 2418. Where, in some embodiments, the dashed line illustrates a planar surface.

[0660] Referring now to Figure 25A showing a simplified schematic cross sectional view of a device 2500 positioned on an eye surface, according to some embodiments of the invention. Referring also to Figure 25B is a simplified schematic cross sectional view of a device 2500, according to some embodiments of the invention. In some embodiments, Figure 25A and Figure 25B illustrate the same device and a same cross sectional view of the same device 2500.

[0661] In some embodiments, device 2500 includes an extending portion 2598 which is not covered by eyelid 2546 e.g. when the eye is open e.g. as illustrated in Figure 25A. Where, in some embodiments, a body 2501 of device 2500 is located underneath eyelid 2546 (e.g. when the eye is open e.g. as illustrated in Figure 25A).

[0662] In some embodiments, extending portion 2598 extends from body 2501 of device 2500 which includes a retention portion 2536.

[0663] In some embodiments, extending portion 2598 is thin and / or has a thin edge. In some embodiments, a step formed between a leading edge 2566 of device 2500 and the eye surface (or a planar surface contacting the device edges) is l-500microns, or l-100microns, or 10-50microns. Thinness and / or the small step potentially presenting less surface area to interact with the eyelid as is moves over the area of the extending portion, e.g. during blinking and / or eyeball movement.

[0664] In some embodiments, extending portion 2598 has a length 2596 of 0.5-6mm. In some embodiments, body 2501 has one or more feature of devices e.g. as described elsewhere in this document. For example, one or more of the devices as described elsewhere in this document having an extending portion 2598 extending from the device leading edge.

[0665] In some embodiments, body 2501 of the device is held in position underneath the eyelid. For example, in some embodiments, body 2501 having a retention portion 2536 which includes one or more feature as described regarding and / or illustrated for retention portion 636 Figures 6A- B and / or elsewhere in this document.

[0666] In some embodiments, slope and / or thickness of retention portion 2536 is measured with respect to an edge 2594 of the retention portion with respect to extending portion 2598 and, for example, not by a leading edge 2566 of the device.

[0667] In some embodiments, extending portion 2598 is used to load a meniscus (the valley between the eyelid edge and the eyeball where the lacrimal / tear fluid accumulates and creates a reservoir of fluid) with one or more material and / or active pharmaceutical ingredient (API).

[0668] Referring now to Figure 26 showing a simplified schematic cross sectional view of a device 2600, according to some embodiments of the invention.

[0669] In some embodiments, a device 2600 has extending portions 2698, 2699 extending from a device body 2601 in more than one direction. In some embodiments, a single extending portion surrounds a device body 2601 footprint. Where device body 2601 includes one or more feature as illustrated in and / or described regarding device body 2501 Figures 25A-B. Where one or both of extending portions 2698, 2699 have one or more feature as illustrated in and / or described regarding extending portion 2598 Figures 25A-B.

[0670] Referring now to Figure 27 A showing a simplified schematic top view of an ophthalmic device 2700, according to some embodiments of the invention. Referring also to Figure 27B is a simplified schematic cross sectional view of an ophthalmic device 2700, according to some embodiments of the invention. Figure 27B illustrates a cross sectional view of device 2700 of Figure 27A, for example, taken along line EE of Figure 27A. In Figure 27A, dotted lines are contour lines of an anterior surface 2716 of device indicating, for the anterior surface, same distances above a height defined by a plane a device footprint as indicated in Figure 27A by a solid line.

[0671] In some embodiments, device 2700 includes more than one retention portion 2736, 2737. Where, in some embodiments, retention portions 2736, 2737 are connected by a connecting portion 2706 which, in some embodiments, has a thickness which is below that required by a retention portion.

[0672] A potential advantage of multiple retention portions is potential retention of the device underneath an eyelid if a retention portion escapes from underneath the eyelid. A potential advantage of having more than one raised portion of the device (e.g. as provided by retention portions) is protruding surfaces easing pinch-removal e.g. as described elsewhere in this document. A potential advantage of having a connecting portion 2706, for example, instead of a single large retention portion is the ability to have a long device with reduced device volume.

[0673] Referring now back to Figure 27A, which, in some embodiments, illustrates another embodiment having (instead of edge 2766), edge 2766a illustrated as a dashed line, which edge 2766a, in some embodiments, has an inlet, for example, extending towards central region 2706 where the central region 2706 has a smaller extent and / or footprint than central region 2706. In some embodiments, a device has a corresponding shape on an opposing edge 2734a illustrated as a dashed line (instead of edge 2734a).

[0674] In some embodiments, cross sections of device 2700 of Figure 27A including edge inlet / s has the same cross sections as described for device 2700 of Figure 27A without inlets.

[0675] Referring now to Figure 27C showing a simplified schematic cross sectional view of a device 2700, according to some embodiments of the invention.

[0676] Figure 27C illustrates an embodiment of one or both devices as illustrated by Figure 27A, where, in some embodiments, each retention portion has a corresponding concave curve 2718a, 2718b, in posterior surface 2718a. Where concave surfaces include one or more feature as described regarding devices with a single retention portion e.g. elsewhere in this document. For example, including one or more feature of posterior surface 616 Figure 6B and / or posterior surface 1516 Figures 15C-D and / or posterior surface 1316 Figure 13B and / or Figure 14. In some embodiments, the surfaces are concave in more than one direction, for example cross section taken along line FF and / or line GG having concave posterior surface, for example the cross section / s having one or more feature as described and / or illustrated regarding the cross section of Figure 13B and / or Figure 14.

[0677] 2.4. Exemplary degradation

[0678] Referring now to Figure 28 showing a process of ophthalmic device degradation, according to some embodiments of the invention. Additionally see Chapter 4 below, regarding degradation according to specific elastomeric matrices, according to some embodiments of the invention. At 2800, in some embodiments, a device positioned within an eye (e.g. underneath an eyelid of the eye) degrades while maintaining structural feature / s of a retention portion. The retention portion acting to maintain the device underneath the eyelid. Where, during degrading, in some embodiments, the device elutes one or more active pharmaceutical ingredients (API). In some embodiments, degradation comprises the loss of mass.

[0679] At 2802, in some embodiments, for example, after degradation and / or disintegration of other portion / s of the device, the retention portion degrades.

[0680] At 2804, in some embodiments, upon degradation of the retention portion, the device exits the eye, for example, upon exiting from underneath the eyelid.

[0681] Figure 29 is a simplified schematic cross sectional view of a device 2900, according to some embodiments of the invention.

[0682] In some embodiments, contours 2910, 2912, 2916, 2926, illustrate an anterior surface of device 2900 over time, e.g. as device 2900 degrades during residence on an eye. In some embodiments, a slope and / or thickness of a retention portion is maintained e.g. through transition of device anterior surface from 2910 to 2912 and 2916 and only afterwards, in some embodiments do thickness (e.g. as illustrated) and / or slope of the retention portion reduce.

[0683] In some embodiments, device 2900 includes different portions with different degradation speeds. Where, in some embodiments, portion 2971 includes material which is less rapidly degraded (or is not degraded within the eye) than other portions of the device. In some embodiments, a less rapidly degraded portion of the device (e.g. portion 2971) is sized and / or shaped and / or positioned with respect to other portions of the device to maintain a retention portion e.g. during degradation of other portion / s of the device.

[0684] Referring now to Figures 30A-B showing simplified schematic cross sectional views of a device 3000, according to some embodiments of the invention.

[0685] In some embodiments, device 3000 includes different portions 3032, 3030 with different degradation times. In some embodiments, a posterior portion 3030 adjacent to a posterior surface 3016 of device 3000 is more rapidly degraded, than an anterior portion 3032 adjacent to an anterior surface 3018 of device 3000. For example as illustrated in transition in the device cross section illustrated in transition between Figure 30A to Figure 30B. In some embodiments, degradation of an anterior surface of device 3000, for example, combined, in some embodiments, with resistance of the device to collapse on the eye surface, maintains a slope and / or height of the device above the eye surface e.g. maintains a retention portion property / ies. 2.5. Exemplary ophthalmic devices

[0686] Referring now to Figure 31A showing a simplified schematic cross section view of an ophthalmic device 3100 on an eye surface 3104, according to some embodiments of the invention. Also referring to Figure 3 IB showing a simplified schematic view of an ophthalmic device 3100, according to some embodiments of the invention. Also referring to Figure 31C showing a simplified schematic view of an ophthalmic device 3100, according to some embodiments of the invention.

[0687] In some embodiments, device 3100 includes a posterior surface 3116 and an anterior surface 3118.

[0688] In some embodiments, device 3100 includes a plurality of layers 3110, 3112. Where, in some embodiments, layers generally follow surfaces of the device.

[0689] In some embodiments, a first layer 3110 is adjacent to and / or in contact with eye surface 3104 and / or forms at least a part of posterior surface 3116. In some embodiments, first layer 3110 includes mucoadhesive material. While explanations were provided in relation to an eye surface, it should be understood that, in some embodiments, as mentioned above, the posterior and anterior surfaces are distinct from each other irrespective of being inside the eye or outside of it. In some embodiments, the posterior and anterior surfaces are shaped differently (e.g., one is convex and the other concave, one curved and the other flat, etc.).

[0690] In some embodiments, a second layer 3112 contacts, at least periodically, an inner surface of an eyelid, and / or forms at least part of anterior surface 3114. In some embodiments, second layer has a smooth outer surface and / or includes lubricious material. In some embodiments, one or both of first and second layers 3110, 3112, include and / or elute therapeutic material / s.

[0691] Figure 3 IB, illustrates determining of an extent of device 3100 where, extent is, one or more dimension and / or average of two or more dimensions of a bounding box 3164 which is a smallest cuboid shape into which device 3100 fits.

[0692] In some embodiments, device 3100 includes one or more additional layer (e.g. as described elsewhere in this document).

[0693] In some embodiments, the ophthalmic device has a thickness 3128 (e.g. a maximum thickness and / or average thickness of a central 50% of the device) of less than 100 microns. In some embodiments, the ophthalmic device has a thickness of between about 1 to about 200 microns. In some embodiments, the device has a thickness of about 1, or about 2, or about 3, or about 4, or about 5, or about 6, or about 7, or about 8, or about 9, or about 10, or about 15, or about 20, or about 25, or about 30, or about 35, or about 40, or about 45, or about 50, or about 55, or about 60, or about 70, or about 80, or about 90, or about 100, or about 110, or about 120, or about 130, or about 140, or about 150, or about 160, or about 170, or about 180, or about 190, or about 200 microns. In some embodiments, the device has a thickness of between about 10 to about 100 microns.

[0694] In some embodiments, a first (e.g. mucoadhesive) layer 3166 and / or a second (e.g. lubricous) layer 3164 and / or an optional additional intermediate layer or layers (e.g. as described elsewhere in this document) has a thickness (e.g. a maximum thickness and / or average thickness at a central 50% of the device) of less than 100 microns. In further embodiments, one or more layer has a thickness of between about 1 to about 200 microns. In some embodiments, lubricious layer and / or a mucoadhesive layer and / or an intermediate layer has a thickness of about 1 microns, 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, 200 microns. In some embodiments, one or more layer has a thickness of between about 1 to about 10 microns.

[0695] In some embodiments, one or more layer has about the same thickness as one or more other layer. In some embodiments, one or more layer has a different thickness than one or more other layer. In some embodiments, one or more layer has non-uniform thickness. For example, thinning from a central region of the device outward towards edge region / s of the device. For example, a layer having cavities and / or holes and / or protrusion / s.

[0696] Referring now to Figures 32-37 showing simplified schematic cross section views of portions of ophthalmic devices, according to some embodiments of the invention. In Figures 32- 37, shaded areas indicate presence of active pharmaceutical ingredient / s (API).

[0697] Referring now to Figure 32 and Figure 35, in some embodiments, a second layer 3212, 3512 (e.g. including one or more feature as described regarding second layer 3112 Figures 31A-C) comprises active pharmaceutical ingredient / s (API). For example, dispersed within second layer 3112 and / or located within one or more region 3514 of second layer 3512.

[0698] Referring now to Figure 33 and Figure 36, in some embodiments, a first layer 3310, 3610 (e.g. including one or more feature as described regarding first layer 3110 Figures 31A-C) comprises active pharmaceutical ingredient / s (API). For example, dispersed within first layer 3110 and / or located within one or more region 3614 of second layer 3610.

[0699] Referring now to Figure 34 and Figure 37, in some embodiments, both a first layer 3410, 3710 (e.g. including one or more feature as described regarding first layer 3110 Figures 31A-C) and a second layer 3412, 3712 (e.g. including one or more feature as described regarding second layer 3112 Figures 31A-C) comprises active pharmaceutical ingredient / s (API). For example, dispersed within first layer 3410 and / or second layer 3412 and / or located within one or more region 3714 of second layer 3712 and / or first layer 3710. Where, in some embodiments, (not illustrated) one of the layers hosts a portion which has therapeutic material and the other layer has therapeutic material dispersed within it. In some embodiments, discrete region / s including therapeutic material include different therapeutic material than those layers which have therapeutic material dispersed within them. In some embodiments, discrete region / s are encapsulated by other material, the material for example, in some embodiments, eroding before the therapeutic material starts to elute into the eye.

[0700] Referring now to Figures 38-44 showing simplified schematic cross sectional views of devices 3800, 3900, 4000, 4100, 4200, 4300, 4400, according to some embodiments of the invention.

[0701] In some embodiments, a device has a posterior surface which is flat or high radius of curvature e.g. posterior surface 3816 of device 3800 Figure 38, e.g. posterior surface 3916 of device 3900 Figure 39, e.g. posterior surface 3406 of device 4000 Figure 40, e.g. posterior surface 4116 of device 4100 Figure 41. Where, in some embodiments, a high radius of curvature is more than 5mm, or more than 10mm, or more than 9.6mm or 8- 12mm, or 9-11mm.

[0702] In some embodiments, a device has a posterior surface which is concave, e.g. posterior surface 4216 of device 4200, e.g. posterior surface 4316 of device 4300, e.g. posterior surface 4416 of device 4400. Where, in some embodiments, concave posterior surface 4216, 4316, 4416, includes one or more feature as illustrated in and / or described regarding concave and / or curved posterior / s elsewhere in this document.

[0703] In some embodiments, a device and / or a cross section of a device includes a single cavity e.g. where, in some embodiments, element 3830, 3930, 4030 of Figures 38-40 respectively is a cavity. Where, in some embodiments, the cavity 3830, 3930, 4030, is disposed on a posterior surface 3816, 3916, 4016, of the device.

[0704] In some embodiments, a device and / or a cross section of a device includes a single portion with different material, for example, mucoadhesive material e.g. where, in some embodiments, element 3830, 3930, 4030 of Figures 38-40 respectively is a cavity. Where, in some embodiments, the mucoadhesive portion 3830, 3930, 4030, is disposed on a posterior surface 3816, 3916, 4016, respectively of the device.

[0705] Referring now to Figure 41 and Figure 42. In some embodiments, a device and / or a cross section of a device has a single portion with different material 4130, 4230 e.g. mucoadhesive material and has a single cavity 4132, 4232. Where, in some embodiments, cavity 4130, 4230 and different material portion 4132, 4232 are disposed on a posterior surface 4116, 4216 of device 4100, 4200 respective.

[0706] In some embodiments, a device and / or a cross section of a device has two portions of different material / s where portions 4130, 4132, of device 4100 and / or portions 4230, 4232 of device 4200 have the same material or different materials.

[0707] In some embodiments, a device 4100, 4200 and / or a cross section of the device has two cavities 4130, 4132, and 4230, 4232 respectively.

[0708] Referring now to Figure 43 and Figure 44, in some embodiments, a device 4300, 4400, has both more than one concavity 4330, 4432 and more than one different material portion 4332, 4432 all of which, in some embodiments, are disposed on posterior surfaces 4316, 4416 of device 4300, 4400 respectively. In some embodiments, one or more of the cavities and / or one or more of the different material portions are located within a body of the device and / or on a different device surface, for example, an anterior surface 4318, 4418 of the device.

[0709] Referring now to Figure 43, in some embodiments, cavity / ies 4330 are disposed on posterior surface 4316 more centrally with respect to surface 4316 and / or device body 4300 than different material (e.g. mucoadhesive) portion / s 4332.

[0710] Referring now to Figure 44, in some embodiments, different material (e.g. mucoadhesive) portion / s 4432 are disposed on posterior surface 4416 more centrally with respect to surface 4416 and / or device body 4400 than cavity / ies 4430.

[0711] Referring now to Figures 45-50 showing simplified schematic cross sectional views of double layer devices 4500, 4600, 4700, 4800, 4900, 5000, according to some embodiments of the invention.

[0712] In some embodiments, device 4500, 4600, 4700, 4800, 4900, 5000, has a posterior surface 4516, 4616, 4716, 4816, 4916, 5016 respectively and an anterior surface 4518, 4618, 4718, 4818, 4918, 5018 respectively.

[0713] In some embodiments, device 4500, 4600, 4700, 4800, 4900, 5000 includes a first layer 4510, 4610, 4710, 4810, 4910, 5010, and a second layer 4512, 4612, 4712, 4812, 4912, 5012. Where, in some embodiments, first layer has one or more feature as described regarding and / or illustrated regarding first layer 3110 Figures 31A-C and / or one or more of first layer 3210, 3210, 3310, 3410, 3510, 3610, 3710, Figures 31A-37 respectively. Where, in some embodiments, second layer has one or more feature as described regarding and / or illustrated regarding second layer 3112 Figures 31A-C and / or one or more of second layer 3212, 3212, 3312, 3412, 3512, 3612, 3712, Figures 31A-37 respectively. In some embodiments, a device has a posterior surface which is flat or has low curvature (e.g. as defined elsewhere in this document) in dry and / or hydrated form. For example, posterior surface 4516 Figure 45, posterior surface 4616 Figure 46, posterior surface 4716 Figure 47, posterior surface 4916 Figure 49.

[0714] Referring now to Figure 45 and Figure 47, in some embodiments, a second layer 4512, 4712 (e.g. containing lubricous material) extends around a body of the device, for example, covering edge / s 4568 of the device and / or forming a part / s (e.g. at edge / s) of a proximal surface of the device 4516, 4716.

[0715] Referring now to Figures 45-47, in some embodiments, a first and / or second layer has about uniform thickness across an area of a device and / or along one or more cross section of the device. For example, layers 4510, 4512 Figure 45, layers 4610, 4612, layer 4712 Figure 47.

[0716] Referring now to Figures 47-50. In some embodiments, one or more layer has one or more of a maximal thickness at a center and / or central region of the device and a reducing thickness moving towards edge / s of the device from the central region. For example, layer 4710 Figure 47, layers 4810, 4812 Figure 48, layers 4910, 4912 Figure 49, layer 5012 Figure 50.

[0717] Figure 45, illustrates a device 4500 with flat and / or low curvature posterior 4516 and anterior surfaces 4518, where second layer 4512 extends around edges of device 4500 to form a portion of anterior surface 4518. Where the layers are individually of about uniform thickness.

[0718] Figure 46, illustrates a device with flat and / or low curvature posterior 4616 and anterior surfaces 4618 and where the layers are individually of about uniform thickness.

[0719] Figure 47, illustrates a device 4700 with flat and / or lower curvature posterior surface 4716 and a convex anterior surface 4718 and where second layer 4712 extends around edges of device 4700 to form a portion of anterior surface 4718. In some embodiments, second layer 4712 is about uniform thickness. In some embodiments, first layer 4710 has a maximal thickness at a center and / or central region of the device and reducing thickness moving towards edge / s of device 4700 from the central region.

[0720] Figure 48, illustrates a device 4800 with both a concave posterior surface 4816 and a convex anterior surface 4818. Where, in some embodiments, both first layer 4810 and second layer 4812, have a maximal thickness at a center and / or central region of the device and reducing thickness moving towards edge / s of device 4800 from the central region.

[0721] Figure 49, illustrates a device 4900 where posterior surface 4916 is flat or has low curvature and where anterior surface 4918 is convex. Where, in some embodiments, both first layer 4910 and second layer 4912, have a maximal thickness at a center and / or central region of the device and reducing thickness moving towards edge / s of device 490 0 from the central region. Figure 50, illustrates a device 5000 where, in some embodiments, posterior surface has a bounding plane which is convex. In some embodiments, posterior has one or more protrusions 5034 and / or one or more cavities 5030. For example, a cross section with two protrusions 5034 defining between them a cavity 5030. In some embodiments, thickness of one or both layers is irregular. In some embodiments, posterior surface 5016 has an irregular shape, a convex shape, or a shape having multiple concavities.

[0722] Referring now to Figures 51-58 showing simplified schematic cross sectional views of multi-layer devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 according to some embodiments of the invention.

[0723] In some embodiments, device 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, has a posterior surface 5116, 5216, 5316, 5416, 5516, 5616, 5716, 5816 respectively and an anterior surface 5118, 5218, 5318, 5418, 5518, 5618, 5718, 5818 respectively.

[0724] In some embodiments, device 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 includes a first (e.g. mucoadhesive) layer 5110, 5210, 5310, 5410, 5510, 5610, 5710, 5810, and a second (e.g. lubricous) layer 5112, 5212, 5312, 5412, 5512, 5612, 5712, 5812. Where, in some embodiments, the first layer has one or more feature as described regarding and / or illustrated regarding first layer 3110 Figures 31 A-C and / or one or more of first layer 3210, 3210, 3310, 3410, 3510, 3610, 3710, Figures 31A-37 respectively. Where, in some embodiments, the second layer has one or more feature as described regarding and / or illustrated regarding second layer 3112 Figures 31 A-C and / or one or more of second layer 3212, 3212, 3312, 3412, 3512, 3612, 3712, Figures 31A-37 respectively.

[0725] In some embodiments, device 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 includes an intermediate layer 5136, 5236, 5336, 5436, 5536, 5636, 5736, 5836, respectively. In some embodiments, the intermediate layer is disposed between the first and second layers. Where, in some embodiments, the intermediate layer is covered by other layers e.g. as illustrated in Figures 51-55 and Figures 57-58. In some embodiments, the intermediate layer includes therapeutic material (e.g. dispersed within the layer and / or in portion / s of the layer).

[0726] Figure 51 illustrates a device 5100 having flat and / or low curvature posterior and anterior surfaces (5116 and 5118, respectively). Where, in some embodiments, second surface extends to cover edges of device 5100 e.g. to enclose sides of intermediate surface 5136. In some embodiments, one or more (e.g. all) of first layer 5110, second layer 5112 and third layer 5136 have about uniform thickness. In some embodiments, a thickness of intermediate layer 5136 is thicker than one or more of the other layers, for example, 1.5-10 times thicker.

[0727] Figure 52 illustrates a device 5200 where a posterior surface 5216 is convex. In some embodiments, thicknesses of a first 5210 and second layer 5212 are about the same and, in some embodiments about uniform. In some embodiments, an intermediate layer 5236 has a thicker central region, reducing in thickness towards edges of device 5200. In some embodiments, an average and / or maximal thickness of intermediate layer 5236 is at 1.5-10 times thicker than thickness of one or both of the first 5210 and second 5212 layers.

[0728] In some embodiments, a convex posterior surface, reduces suction between the eyeball and the device, potentially increasing comfort of the device for a user and / or easing removal of the device. In some embodiments, a device includes shape of anterior 5216 and posterior surfaces 5218 of device 5200 of Figure 52 but has a different layer structure and / or interior composition as described in the previous paragraph.

[0729] Figure 53 illustrates a device 5300 where each of a first layer 5310, an intermediate layer 5336, and a second layer 5312 have a thicker central region, the layers reducing in thickness towards edges of device 5300. In some embodiments, second layer 5312 is disposed around device 5300 to form part of posterior surface 5316. In some embodiments, posterior surface 5316 has higher radius of curvature than anterior surface 5318 (e.g. radius of curvatures including one or more feature as described elsewhere in this document e.g. in the overview section)

[0730] Figure 54 illustrates a device 5400 where each of a first layer 5410, an intermediate layer 5436, and a second layer 5412 have a thicker central region, the layers reducing in thickness towards edges of device 5400. In some embodiments, thicknesses of the layers are about the same at a central region of the device and / or throughout one or more cross section of the device.

[0731] In some embodiments, device 5500 of Figure 55 has the same features as device 5100 of Figure 51 except intermediate layer 5536 is, in some embodiments, about the same thickness as one or both of a first layer 5510 and a second layer 5512.

[0732] Figure 56, illustrates a device 5600 where each layer 5610, 5612, 5636, have constant thickness along the illustrated cross section. In some embodiments, intermediate layer 5636 includes therapeutic material. In some embodiments, intermediate layer 5636 is thicker than one or both of the other layers 5612, 5610. For example, a thickness of 1.5-10 times that of the mucoadhesive 5610 and / or lubricious 5612 layers. In some embodiments, intermediate layer 5636 includes a plurality of layers.

[0733] Figure 57 illustrates a device 5700 which has a convex anterior surface 5718, and a flat or low curvature posterior surface 5716. In some embodiments, mucoadhesive layer 5716 has uniform thickness across one or more cross section of the device. In some embodiments, lubricous layer 5712 has uniform thickness on its path around a circumference of intermediate layer 5736. In some embodiments, intermediate layer 5736 is thicker in a central region of one or more cross section of device 5700 and, in some embodiments, has reducing thickness towards edge / s of the device. In some embodiments, lubricous layer 5712 does not form part of posterior surface 5716.

[0734] Figure 58 illustrates a device 5800 which has a convex anterior surface 5818, and a concave posterior surface 5816. In some embodiments, mucoadhesive layer 5816 has uniform thickness across one or more cross section of the device. In some embodiments, lubricous layer 5812 has uniform thickness on its path around a circumference of intermediate layer 5836. In some embodiments, intermediate layer 5836 is thicker in a central region of one or more cross section of device 5800 and, in some embodiments, has reducing thickness towards edge / s of the device. In some embodiments, lubricous layer 5812 does not form part of posterior surface 5816.

[0735] Referring now to Figure 59A showing a simplified schematic cross section of an ophthalmic device 5900, according to some embodiments of the invention.

[0736] In some embodiments, device 5900 includes both a retention portion 5936 (e.g. including one or more feature as described regarding retention portions elsewhere in this document) and a thin edge 5971.

[0737] In some embodiments, an edge (e.g. circumferential edge) of the device has average thickness 5969, at distance 5967, as defined as a shortest distance between a posterior surface 5916 and an anterior surface 5918 of the device, of about 15 microns, or about 20 microns, or about 30 microns or about 50 microns. In some embodiments, the ophthalmic device has a thin edge 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.

[0738] In some embodiments, distance 5967 is 0.1- 1mm, or 0.1-0.5mm of the device. In some embodiments, distance 5967 is about 0.1mm, or about 0.5 mm.

[0739] In some embodiments, thin edge 5971 extends for a region of device 5900. For example, a portion of a circumferential edge of the device. For example, for 20-99%, or 80-90%, of a circumference of the device. For example, for a side of a device e.g. for the trailing edge only or the leading edge only. For example, for more than one side of the device e.g. leading edge and trailing edge, e.g. two opposing sides.

[0740] Figure 59A illustrates device 5900 in a relaxed state.

[0741] Figure 59B is a simplified schematic cross section of an ophthalmic device 5900, according to some embodiments of the invention.

[0742] Figure 59B illustrates the device of Figure 59A when in position of an eye surface (e.g. underneath an eyelid). In some embodiments, thin edge 5971 is flexible and conforms to an eye surface 5904, when device 5900 is on the eye surface. Referring now to Figure 60 showing a simplified schematic cross section of an ophthalmic device, according to some embodiments of the invention.

[0743] Figure 60 illustrates the device of Figure 59A when in position on an eye surface, where the thin edge recesses into the eye surface, for example, as described in the overview section of this document.

[0744] Referring now to Figure 61 showing a simplified schematic cross section of an ophthalmic device 6100, according to some embodiments of the invention.

[0745] In some embodiments, device 6100 has a convex posterior surface 6116. In some embodiments, device 6100 has a retention portion 6136 which includes one or more feature of retention portions as described elsewhere in this document (e.g. retention portion 636 Figure 6B) where, in some embodiments, heights are measured from an eye surface 6104 e.g. as illustrated by vertical arrows in in Figure 61.

[0746] Alternatively, in some embodiments, heights are measured from a planar surface on which the device rests. Alternatively, in some embodiments, heights are measured from a plane 6199 connecting edges (or a majority of a circumferential edge) of the device or from a plane which delineates a largest area cross section of the device, the plane being located between anterior 6118 and posterior surfaces 6116.

[0747] Referring now to Figure 62A showing a simplified schematic cross sectional view of a portion of an eye surface, according to some embodiments of the invention.

[0748] Referring now to Figure 62B showing a simplified schematic cross section view of an ophthalmic device 6200 on an eye surface, according to some embodiments of the invention.

[0749] Referring now to Figure 62C showing a simplified schematic cross section view of an ophthalmic device 6200 on an eye surface, according to some embodiments of the invention.

[0750] In some embodiments, above a stroma 6260 is an eye epithelial layer 6258 over which resides an aqueous tear film layer 6256, above which resides a lipid layer 6254.

[0751] Figure 62A illustrates a cross section of eye anatomy, for example prior to application of device 6200 on the eye.

[0752] Figure 62B illustrates device 6200 and eye anatomy immediately and / or soon after application of device 6200.

[0753] Figure 62C illustrates device 6200 and eye anatomy a time period after application of device where, in some embodiments, the time period is about 1 minute to 1 hour after application.

[0754] In some embodiments, as shown for example in Figure 62B, device body 6200 includes a posterior surface 6216 and an anterior surface 6218. In some embodiments, body 6200 tapers in thickness towards edges of the body. In some embodiments, device 6200 includes cavities 6230, 6232 which, in some embodiments, are disposed on posterior surface 6216.

[0755] In some embodiments, after application of the device tear fluid fills cavities 6232, 6234 epithelial 6258 as before application of the device. In some embodiments, tear fluid e.g. an aqueous and / or a lipid covers the device (not illustrated).

[0756] In some embodiments, as shown for example in Figure 62C, after a time period, in eye tissue conforms to a shape of device 6200. For example, epithelial tissue 6258 locally protrudes 6260 towards cavities 6230 / 6232 e.g. under suction at the cavity entrances. Potentially epithelial protrusion / s 6260 anchor device 6200 in position e.g. reducing likelihood of movement and / or expelling of the device.

[0757] Referring now to Figures 63A-C are simplified schematic cross sectional views of a portion of a device 6300 on an eye surface 6358, according to some embodiments of the invention.

[0758] Figure 63A shows device 6300 and eye anatomy 6358 immediately and / or soon after application of device 6300.

[0759] Figure 63B illustrates device 6300 and eye anatomy 6358 a first time period after application of device. Where, in some embodiments, a first time period is 1 minute to 1 hour.

[0760] Figure 63C illustrates device 6300 and eye anatomy 6358 a second time period after the cross section illustrated in Figure 63B, for example, a further 1 minute to 1 hour after illustration of device 6300 and eye anatomy 6358 in Figure 63B.

[0761] In some embodiments, as shown for example in Figure 63A, device body 6300 includes a posterior surface 6316 which includes a cavity 6330 and a protrusion 6334.

[0762] In some embodiments, after application of the device, tear fluid fills cavity 6330, and epithelial 6358 is as before application of the device.

[0763] In some embodiments, as shown for example in 63B, after a first time period, eye tissue conforms to a shape of device 6300. For example, epithelial tissue 6358 locally protrudes to form protrusion 6360 towards cavity 6330 and / or recesses to form a recession 6362 in pliable epithelia tissue at a region adjacent to protrusion 6334. Where recessed material, in come embodiments, potentially anchors device 6300, potentially reducing likelihood of movement and / or expelling of device 6300.

[0764] In some embodiments, as shown for example in Figure 63C, biodegrading and / or bioerosion and / or mechanically erosion of device 6300 has occurred. Where, in some embodiments, protrusion 6334 has reduced in size (e.g. in one or more dimension) and / or comer / s of protrusion 6334 have rounded. Where, in some embodiments, cavity 6330 corners have been rounded. In some embodiments, (not illustrated) the cavity becomes broader in one or more dimension and / or changes depth e.g. becomes shallower or deeper.

[0765] In some embodiments, proximal surface 6316 of Figure 63C illustrates exemplary proximal surface shape, for example, including protrusion / s 6334 and / or cavity / ies 6330.

[0766] Referring now to Figures 64-66 showing simplified schematic cross sectional views of multi-layer devices 6400, 6500, 6600, according to some embodiments of the invention.

[0767] Figures 64-66, illustrate active pharmaceutical ingredient (API) elution as illustrated in the figures by arrows.

[0768] In some embodiments, as shown for example in Figure 64, an intermediate layer 6436 includes therapeutic material and is not covered by other layer / s (6412, 6410) at edges of device 6400. The layer, in some embodiments, eluting active pharmaceutical ingredient / s (API) through edges e.g. as illustrated by arrows (and optionally not via surfaces 6418, 6419).

[0769] In some embodiments, as shown for example in Figure 65, (e.g. alternatively or additionally to eluting through edges of the device) an intermediate layer 6536 includes therapeutic material and is not fully covered by a second lubricous layer 6512, active pharmaceutical ingredient / s (API) eluting through the second layer. For example, through channel / s and / or holes 6530 in the layer 6512 e.g. as illustrated by arrows on Figure 65. In some embodiments, alternatively or additionally to having channel / s and / or holes, second layer 6512 includes material which allows diffusion through the material of active pharmaceutical ingredient / s (API). In some embodiments, active pharmaceutical ingredient / s (API) eluting is not performed via surfaces 6518 of layer 6512 or 6516 of 6510.

[0770] In some embodiments, as shown for example in Figure 66, (e.g. alternatively or additionally to eluting through edges and / or through a second lubricious surface 6612 of the device) an intermediate layer 6636 includes therapeutic material and is not fully covered by a first mucoadhesive layer 6610, active pharmaceutical ingredient / s (API) eluting through the first layer. For example, through channel / s and / or holes 6630 in the layer 6610 e.g. as illustrated by arrows on Figure 66. In some embodiments, alternatively or additionally to having channel / s and / or holes, first layer 6610 includes material which allows diffusion through the material of active pharmaceutical ingredient / s (API).

[0771] Referring now to Figures 67A-F showing simplified schematic cross sections of a portion of a device as residence time of the device progresses, according to some embodiments of the invention.

[0772] Referring now to Figure 68 showing a flowchart of a disintegration progression of a device, according to some embodiments of the invention. Figure 67 A, illustrates the device layer structure before the device is placed on an eye surface. The device including a first mucoadhesive layer 6710, an intermediate layer 6736 and a second lubricous layer 6712.

[0773] At 6800, in some embodiments, device 6700 is positioned on an eye surface 6758.

[0774] At 6802, in some embodiments, lubricous layer 6712 degrades and / or dissolves and / or erodes, for example, transitioning device 6700 from the configuration illustrated in Figure 67B to that illustrated in Figure 67C.

[0775] At 6804, in some embodiments, intermediate layer 6736 partially degrades and / or dissolves and / or erodes, for example, transitioning device 6700 from the configuration illustrated in Figure 67C to that illustrated in Figure 67D and then to that illustrated in Figure 67E.

[0776] At 6806, in some embodiments, mucoadhesive layer 6710 dissolves, and / or degrades and / or erodes, for example, transitioning the eye from the configuration illustrated in Figure 67E to that illustrated in Figure 67F.

[0777] Referring now to Figures 69A-C showing simplified schematic cross sections of a device 6900 as residence time of the device progresses, according to some embodiments of the invention.

[0778] In some embodiments, Figures 69A-C illustrate a portion of a device (e.g. a central portion, where edges are not illustrated).

[0779] In Figures 69A-C, in some embodiments, like shading indicates portions with the same material characteristics (e.g. lubricious, mucoadhesive, containing therapeutic material).

[0780] In some embodiments, device 6900 includes a posterior surface 6916 and an anterior surface 6918, where one or both of surfaces 6916, 6918 have one or more feature (e.g. curvature, thickness) as illustrated and / or described elsewhere in this document.

[0781] In some embodiments, device 6900 includes a first mucoadhesive layer 6910, and a second lubricious layer 6912.

[0782] Where, in some embodiments, mucoadhesive layer 6910 covers most (e.g. over 55-99%, or 60-90%) or all of posterior surface 6916. A potential benefit of a mucoadhesive layer with a large surface area is increased stability, for example, associated with increased adhesion to the eye surface.

[0783] Where, in some embodiments, lubricious layer 6912 covers a portion of anterior surface 6918 e.g. edge region / s.

[0784] In some embodiments, device 6900 includes a third layer 6970. Where, in some embodiments, third layer 6970 includes rapidly dissolving and / or degrading and / or abrading material. Where, in some embodiments, the third layer disintegrates more rapidly than other layer / s of the device 6900. For example, as illustrated in transition between Figure 69A and Figure 69B where third layer 6970 has reduced in thickness.

[0785] In some embodiments, mucoadhesive layer 6910 is also more readily eroded (e.g. associated with proximity to the eye surface which is not illustrated and / or associated with material characteristics of the layer) and / or dissolved and / or degraded (e.g. associated with material characteristics) than one or more other layer of the device. For example, as illustrated in transition between Figure 69A and Figure 69B where mucoadhesive layer 6910 has reduced in thickness.

[0786] In some embodiments, intermediate layer 6936 includes therapeutic material, where upon being revealed by disappearance of third layer 6970, intermediate layer 6936 begins to dissolve and / or degrade and / or erode, e.g. eluting medication. In some embodiments, intermediate layer is more readily dissolved and / or degraded and / or eroded than one other layer e.g. lubricious layer 6912 and / or mucoadhesive layer 6916 e.g. as illustrated by cavities 6930 having formed in intermediate layer 6936.

[0787] Referring now to Figures 70A-D showing simplified schematic cross sections of a device as residence time of the device progresses, according to some embodiments of the invention.

[0788] Figures 70A-C illustrate a portion of a device (e.g. a central portion, where edges are not illustrated).

[0789] In Figures 70A-C, in some embodiments, like shading indicates portions with the same material characteristics (e.g. lubricious, mucoadhesive, containing therapeutic material).

[0790] In some embodiments, device 7000 has a posterior surface 7016 and an anterior surface 7018, where one or both of surfaces 7016, 7018 have one or more feature (e.g. curvature, thickness) as illustrated and / or described elsewhere in this document.

[0791] In some embodiments, device 7000 includes a first mucoadhesive layer 7010, and a second lubricious layer 7012. In some embodiments, device 7000 includes an intermediate therapeutic material 7036 layer.

[0792] Where, in some embodiments, one or more than one of (e.g. all of) lubricious layer 7012, mucoadhesive layer 7016, are disposed at edge region / s of device 7000, for example, not being present in a central region of device 7000.

[0793] In some embodiments, device 7000 includes a third layer 7070. Where, in some embodiments, third layer 7070 includes rapidly dissolving and / or degrading and / or abrading material. Where, in some embodiments, the third layer disintegrates more rapidly than other layer / s of the device 7000. For example, as illustrated in progression from Figure 70A, to Figure 70B, to Figure 70C where third layer 7070 reduces in thickness and then in transition between Figure 70C to Figure 70D where third layer 7070 disappears. In some embodiments, e.g. illustrated in transition between Figure 70A to Figure 70B, mucoadhesive layer 7010 disappears first, e.g. exposing intermediate therapeutic material layer 7036. In some embodiments, third layer 7070 disappears leaving one or more remaining layer / s at edges of device e.g. as illustrated in Figure 70D. In some embodiments, device 7000 is placed over a region of the eye e.g. covering a cornea, where disappearance of third layer 7070 creates a hole in the device e.g. to position device 7000 on sclera surrounding cornea.

[0794] Referring now to Figure 71 is a simplified schematic cross section of a device 7100, according to some embodiments of the invention.

[0795] Figure 71 illustrates a portion of a device (e.g. a central portion, where edges are not illustrated).

[0796] In Figure 71, like shading indicates portions with the same material characteristics (e.g. lubricious, mucoadhesive, containing therapeutic material).

[0797] In some embodiments, device 7100 has a posterior surface 7116 and an anterior surface 7118, where one or both of surfaces 7116, 7118 have one or more feature (e.g. curvature, thickness) as illustrated and / or described elsewhere in this document.

[0798] In some embodiments, device 7100 includes a first mucoadhesive layer 7110, and a second lubricious layer 7112. In some embodiments, device 7100 includes an intermediate therapeutic material 7136 layer. In some embodiment, mucoadhesive layer 7110 covers most or all of device posterior surface 7116.

[0799] Where, in some embodiments, one or more than one of lubricious layer 7112, and intermediate therapeutic material layer 7136, are disposed at edge region / s of device 7100, for example, not being present in a central region of device 7100.

[0800] In some embodiments, device 7100 includes a third layer 7170. Where, in some embodiments, third layer 7170 includes rapidly dissolving and / or degrading and / or abrading material. Where, in some embodiments, the third layer disintegrates more rapidly than other layer / s of the device 7100.

[0801] In some embodiments, device 7100 includes a degradable layer 7172, which, in some embodiments, degrades more rapidly than one or more of mucoadhesive layer 7110, lubricious layer 7112 and therapeutic layer 7136. Where, in some embodiments, degradable layer 7172 degrades and / or dissolves and / or erodes less rapidly than third layer 7170.

[0802] Where, in some embodiments, third layer 7170 is first to disappear, for example, revealing portion / s of therapeutic layer 7136 to initiate and / or increase therapeutic material elution. Where, in some embodiments, degrading layer 7172 then erodes e.g. to further reveal the therapeutic material layer and / or to disintegrate the device. Referring now to Figure 72 showing a simplified schematic cross section of a device 7200, according to some embodiments of the invention.

[0803] In some embodiments, device 7200 has a posterior surface 7216 and an anterior surface 7218, where one or both of surfaces 7216, 7218 have one or more feature (e.g. curvature, thickness) as illustrated and / or described elsewhere in this document.

[0804] In some embodiments, anterior surface 7218 includes a low curvature (or flat) region disposed at a central region of device 7200. In some embodiments, curves towards posterior surface 7216.

[0805] In some embodiments, device 7200 includes a first mucoadhesive layer 7210, and a second lubricious layer 7212. In some embodiments, device 7200 includes an intermediate therapeutic material 7236 layer. In some embodiments, second surface 7212 curves around edge / s of device 7200, for example, in some embodiments, forming an edge portion of posterior surface 7216.

[0806] In some embodiment, mucoadhesive layer 7210 occupies edge regions of device 7200 and / or posterior surface 7216.

[0807] A potential advantage mucoadhesive being disposed locally at edges of device 7200 e.g. as recessions in intermediate therapeutic material 7236 layer is adhesive advantages of mucoadhesive material while maintaining more of a volume of the device for therapeutic material. In some embodiments, intermediate therapeutic material layer 7236 forms at least a part of posterior surface 7216. A potential benefit being ingredient elution rapidly after attachment of device 7200 to an eye surface.

[0808] Referring now to Figures 73A-B showing simplified schematic cross sectional views of a device 7300 on an eye surface 7304, according to some embodiments of the invention.

[0809] For simplicity, device 7300 is illustrated as having a rectangular cross section, however device 7300, in some embodiments, has a shape (shape e.g. including curvature of a posterior and / or anterior surface of the device) having one or more feature of device / s described elsewhere within this document.

[0810] In some embodiments, device 7300 includes a layer 7312 which includes therapeutic material particles 7336. Where material particles 7336, in some embodiments, include one or more feature of microparticles and / or nanoparticles e.g. as described elsewhere in this document.

[0811] In some embodiments, material particles 7336 are devices having retention portions, for example, as described elsewhere in this document. Where, in some embodiments, device 7300 includes 1-10 particles 7336 e.g. each having a retention portion.

[0812] Where, in some embodiments, other material of layer 7312 is rapidly dissolvable and / or degradable and / or erodible. Erosion, in some embodiments, revealing and allowing dispersion of particles 7336, for example, as shown in transition between Figure 73 A to Figure 73B. In some embodiments, e.g. alternatively to what is illustrated in Figure 73B, particles are dispersed within the eyelid and remain underneath the eyelid, for example, retention portions meaning that eye tissue retains the particles 7336 underneath the eyelid.

[0813] In some embodiments, particles 7336 include therapeutic material. Optionally, in some embodiments particles 7336 include mucoadhesive material. Potentially, once a particle is released from layer 7312 if it contacts eye surface 7304 (e.g. under movement / s of one or more of the eyelid, eyeball, and tear fluid) it adheres to the eye surface. In some embodiments, particles adhere to one or more mucosal surface e.g. including 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) to release therapeutic material to eye tissue.

[0814] Optionally, in some embodiments, device includes one or more additional layer (e.g. than layer 7312). For example, in some embodiments, device 7300 includes a mucoadhesive layer 7310.

[0815] In some embodiments, therapeutic material layer 7312 including particles is incorporated into one or more of the device embodiments as described within this document. Including, for example, covering and / or access features to therapeutic material layer 7312.

[0816] Referring now to Figures 74A-D showing simplified schematic cross sectional views of a film, according to some embodiments of the invention.

[0817] Figures 74A-D illustrate cross sections views of a portion of a device. Figures 74A-D show different, portions, for example, sequential portions, of a manufacture process, according to some embodiments of the invention.

[0818] Referring now to Figure 75 showing a method of manufacture, according to some embodiments of the invention.

[0819] In some embodiments, as shown for example in Figure 74A, a substrate 7474 is a film e.g. including one or more feature of films as described elsewhere in this document. For example, in some embodiments, the film includes a single layer. For example, in some embodiments, the film includes a plurality of layers e.g. each layer with different composition and / or material characteristics.

[0820] At step 7500, and, for example, referring to Figure 74B: In some embodiments, cavity / ies are made in substrate 7474. For example, by and / or using one or more of; Jigs, Press, Punch, Laser engraving, drilling, Molecularly imprinted polymer (MIP), 3D printing.

[0821] At step 7502, and, for example, referring to Figure 74C: In some embodiments, cavity / ies are filled e.g. with a different material 7478 to that of substrate 7474. At step 7504, and, for example, referring to Figure 74D: In some embodiments, one or more additional layer 7480 is applied on top of the substrate layer 7474. In some embodiments, additional layer 7480 has different characteristics (e.g. different material characteristics) than other portion / s 7474, 7478.

[0822] In some embodiments, substrate 7474 includes mucoadhesive material, filling material 7478 includes therapeutic material, and additional layer 7480 includes lubricous material.

[0823] Referring now to Figures 76A-C showing simplified schematic cross sectional views of a device 7600, according to some embodiments of the invention.

[0824] In some embodiments, device 7600 includes a first layer 7610 and a second layer 7612. In some embodiments, a device posterior surface 7616 is concave. In some embodiments, the concavity is filled with an additional material 7636. For example, during manufacture and / or by a user, for example just prior to use. Where, in some embodiments, additional material 7636 includes active pharmaceutical ingredient / s (API). Where, in some embodiments, additional material 7636 includes mucoadhesive. Where, in some embodiments, device 7600 is used to extend residence time of a topical application in contact with the eye. For example, where device 7600 seals to an eye surface 7604 holding additional material 7637 in contact with the eye surface e.g. for a time period which is, in some embodiments, longer than residence time of eye drops and / or ointment for example. Where, in some embodiments, the time period is 10 minutes to 12 hours, or 10 minutes to 2 hours.

[0825] In some embodiments, device 7600 includes lubricous material 7612 and / or mucoadhesive material 7610.

[0826] 2.5. Exemplary methods of treatment

[0827] In some embodiments, an exemplary method of treating an eye, comprises inserting an ophthalmic device according to any one of the embodiments as disclosed herein, between an eyelid and a surface of said eye; and allowing the release or releasing at least one medication into said eye. In some embodiments, inserting comprises inserting under an inferior eyelid. In some embodiments, inserting comprises inserting under a superior eyelid. In some embodiments, inserting comprises inserting behind a tarsal plate in said eye. In some embodiments, inserting comprises positioning said device on a bulbar conjunctiva and at least partially underneath said eyelid. 2.6. Exemplary materials

[0828] In some embodiments, one or more portions of an ophthalmic device includes one or more of; film forming agent / s, plasticizer / s, binder / s, and excipient / s.

[0829] In some embodiments the device contains one or more of anti-infective and antiinflammatory pharmacotherapies (including: Glucocorticoids, NTHEs, and biological agents or combination of them) and other technologies and means, such as: silver, gold, zinc oxide, titanium dioxide, selenium, copper, polyammonium salts, signaling inhibiting and antimicrobial peptides, cytokines, enzymes.

[0830] In some embodiments, the device comprises Thermosensitive and / or PH-sensitive and / or Ion sensitive compounds.

[0831] Without being bound by theory, the molecular weight of the compounds and / or a degree of cross-linking within materials of the device contribute to device consistency (e.g. hardness and / or rigidity) and / or contribute to the device rheological properties (e.g. viscosity). Where, in some embodiments, molecular weight and / or cross-linking and / or consistency and / or rheological properties define the device residence time and / or active pharmaceutical ingredient (API) release rate.

[0832] In some embodiments the device composition comprises at least one charged compound. In some embodiments the device composition comprises at least one charged compound and at least one compound having an opposite charge, constructing a PEC (Poly Electrolyte Complex) formation upon liquid adsorption.

[0833] Non-limiting exemplary material / s for:

[0834] A non-degradable portion one or more degradable portion e.g. including one or more fast degrading portion one or more slower degrading portion a lubricious portion (e.g. a lubricious layer and / or film) and / or a mucoadhesive portion (e.g. a mucoadhesive layer and / or film) and / or other portion / s of the ophthalmic device include one or more of (and / or similar compound / s and / or material / s and / or polymer / s and / or combinations thereof) are herein listed:

[0835] Polyethylene-Phthalate polymer film; e.g. purchased as film (MYLAR- A®; DuPont, USA).

[0836] Polyvinyl Alcohol 4-88; e.g. purchased as powder (Merck, Germany).

[0837] Methocel LV-50; e.g. purchased as powder (DOW, USA).

[0838] Poly-Vinyl- Alcohol; e.g. purchased as powder (Merck, Germany). Poly-Vinyl-Alcohol[PVA]:Poly-Ethylene-Glycol[PEG] graft-copolymer; e.g. e.g. purchased as powder (Kollicoat-IR®; BASF, Germany).

[0839] Hydroxy-Propyl-Cellulose polymer; e.g. purchased as powder (Klucel-LF®; Ashland, USA) Povidone (Kollidone 25; BASF, Germany).

[0840] Carbomer, Carbopol, Carbopol 971, Carbopol 974, Carbopol 934, Carbopol 2020.

[0841] Cross-linked Poly-Acrylic-Acid; e.g. purchased as powder (Carbopol 974; Eubrizol, USA).

[0842] Cross-linked Sodium Polyacrylic-Acid; e.g. purchased as powder (FavorPac®; Evonik, Germany).

[0843] Cross-linked Sodium Polyacrylic-Acid; e.g. purchased as powder (Euquasorb®; BASF, USA).

[0844] CMC Sodium, Polycarbophil, Tragacanth, Poly acrylic acid polymers, Sodium alginate, (Poly) Hydroxy Ethyl Cellulose, HPMC, Gum Karaya, Gelatin, Guar Gum, Starch, Modified starch, Pectin, Psyllium, Amberlite -Resin, Hydroxy Propyl cellulose.

[0845] Chitosan; e.g. purchased as powder (KiOnutrime-CsG; kitozyme, Belgium).

[0846] Chitosan; e.g. purchased as powder (Chitoclear; Premix, Iceland or 90 / 200 / A1; Kraeber, Germany or Protasan UP CE 114, 113, 213, 214; Novamatrix, Norway).

[0847] Alginate, Gellan gum, Eudragit.

[0848] Polyethylene oxide, Carboxymethyl cellulose (CMC), Poly(methyl vinyl ether), Poly(methyl vinyl ether) co maleic anhydride, Hydroxy Propyl methyl cellulose, Methyl Ethyl cellulose, poly hydroxyethyl methacrylate.

[0849] Methylcellulose or hypromellose or Povidone (Kollidone 25; BASF, Germany), or polyvinyl pyrrolidone (PVP).

[0850] Cross-linked Poly Glutamic-Acid; e.g. purchased as powder (PGA; hayashibira, Japan).

[0851] Cross-linked Dextrane gel; e.g. purchased as powder (Sephadex G-100; GE Medical).

[0852] Lactose monohydrate; e.g. purchased as powder (Pharmatose 200, Fonterra, New Zealand).

[0853] Cellulose acetate, Ethyl cellulose, Methyl cellulose...

Claims

WHAT IS CLAIMED IS:

1. An ophthalmic device, configured to reside between an eye surface of an eyeball and an eyelid, comprising: a body made of an elastomeric matrix, wherein said elastomeric matrix comprises: water, one or more types of PVOH, and one or more organic plasticizers, said body characterized by: i. a posterior surface which is adjacent to an eye surface when said ophthalmic device is worn; ii. an anterior surface, which is adjacent to said eyelid covering said eye surface when said ophthalmic device is worn; iii. a retention portion, defined between a portion of said anterior surface and a portion of said posterior surface; wherein a combined mass ratio of said one or more organic plasticizers to said one or more types of PVOH is at least 2:1.

2. The ophthalmic device according to claim 1, wherein said retention portion is configured to cause the ophthalmic device to move with the eyelid when the eyelid moves in respect to the eyeball.

3. The ophthalmic device according to claim 1 or claim 2, wherein an angle of a slope of said anterior surface extending from said posterior surface is larger than 45 degrees.

4. The ophthalmic device according to any one of claims 1-3, wherein a relation between a width and a length of said ophthalmic device is from about 1:1 to about 1:3.

5. The ophthalmic device according to any one of claims 1-4, wherein said body swells isotropically when immersed in simulated tear fluid for 15 minutes or less.

6. The ophthalmic device according to any one of claims 1-5, further comprising at least one ophthalmic acceptable active pharmaceutical ingredients (API).

7. The ophthalmic device according to any one of claims 1-6, wherein said water makes between 5 wt% and 50 wt% of said elastomeric matrix.

8. The ophthalmic device according to any one of claims 1-7, wherein said ophthalmic device is configured to gain no more than 50% weight when immersed in simulated tear fluid for 15 minutes or less.

9. The ophthalmic device according to any one of claims 1-8, wherein said ophthalmic device is obtainable from a liquid solution comprising water, the ophthalmically acceptable active pharmaceutical ingredient (API), the PVOH, and the water-soluble organic liquids, without freezing.

10. The ophthalmic device according to any one of claims 1-9, comprising two or more types of PVOH.

11. The ophthalmic device according to claim 10, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device disintegrates under simulated tear fluid (STF) within 24 hours.

12. The ophthalmic device according to claim 10, wherein a ratio between said two or more types of PVOH is such that said ophthalmic device remains intact in simulated tear fluid (STF) during the first 10 minutes.

13. The ophthalmic device according to any one of claims 1-12, wherein said ophthalmic device is visible to naked eye on a background of bulbar conjunctiva.

14. The ophthalmic device according to any one of claims 1-13, wherein said ophthalmic device is elongated and symmetrical, so that all orientations of the device are equivalent as long as an elongated side of the device lies at a given direction.

15. The ophthalmic device according to any one of claims 1-14, wherein said retention portion is defined by heights between said posterior surface and said anterior surface; and wherein a first height of said heights measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height of said heights measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

16. The ophthalmic device, according to any one of claims 1-15, wherein said body includes a plurality of ophthalmic lubricants.

17. The ophthalmic device, according to claim 16, wherein each of said plurality of ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, a polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or pharmaceutically acceptable salt thereof, cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropyl methylcellulose, and povidone.

18. The ophthalmic device according to any one of claims 1-17, wherein said PVOH comprises PVOH of two or more types that differ from each other by chain length, degree of hydrolysis, or both.

19. The ophthalmic device according to claim 18, wherein at least 35 %wt of said two or more types of PVOH has a degree of hydrolysis lower than 90%.

20. The ophthalmic device according to claim 16, wherein said ophthalmic lubricants comprise polyethylene glycol (PEG), and the mass content of the PEG in the elastomeric matrix is about equal that of the PVOH.

21. The ophthalmic device according to claim 16, wherein at least 35% of said ophthalmic lubricants consist of glycerol and propylene glycol.

22. The ophthalmic device according to any one of claims 1-21, wherein said elastomeric matrix is impregnated with an ophthalmically acceptable active pharmaceutical ingredient.

23. The ophthalmic device according to any one of claims 1-22, obtainable by mixing the API with water and ophthalmic demulcents to obtain a mother solution; and drying the mother solution at room temperature.

24. The ophthalmic device according to claim 23, obtainable without heating the mother solution.

25. The ophthalmic device according to any one of claims 22-24 obtainable without heating the API.

26. The ophthalmic device according to any one of claims 1-25, wherein said ophthalmic device is characterized by at least one of the following mechanical properties: a. tensile strength of between 0.05 MPa and 10 MPa; b. Young modulus of between 0.05 MPa and 10 MPa; and c. elongation at break of between 50% and 1000%.

27. The ophthalmic device according to any one of claims 1-26, wherein said ophthalmic device is configured to lose at least 50% of its weight within 2 hours in an eye.

28. The ophthalmic device according to any one of claims 1-27, wherein said retention portion is configured to keep said ophthalmic device in place when the device is worn, and the eye is rolled.

29. The ophthalmic device according to any one of claims 1-28, wherein a first height perpendicular to a reference surface and measured from a first point on said posterior surface to a corresponding point on said anterior surface differs by at least 1mm, from a second height perpendicular to the reference surface and measured from a second point on said posterior surface to a corresponding point on said anterior surface, said second point being distanced at most 1mm from said first point.

30. The ophthalmic device according to any one of claims 1-29, sized and shaped to be fully covered by the lower eyelid when worn under a lower eyelid.

31. The ophthalmic device according to any one of claims 1-30, wherein said ophthalmic device is configured for self-administration.

32. The ophthalmic device according to any one of claims 1-31, wherein said device is configured for wearing away from a fornix’ eye.

33. The ophthalmic device according to any one of claims 1-32, comprising two or more types of PVOH and wherein each of said two or more types of PVOH constitutes at least 10% of the total amount of PVOH in the matrix.

34. The ophthalmic device according to any one of claims 1-33, comprising two or more types of PVOH and wherein the two or more types of PVOH include one type that has long chains and is fully hydrolyzed, and one type that has at least one of:a. short chains and is partially hydrolyzed; b. long chains and is partially hydrolyzed; c. short chains and is fully hydrolyzed.

35. The ophthalmic device according to claim 34, wherein: a. short chains are of 200 to 2000 monomeric units; b. long chains are of 2200 to 5000 monomeric units; c. fully hydrolyzed PVOH is of hydrolysis degree of 97% or more; and d. partially hydrolyzed is of hydrolysis degree of 95% or less.

36. The ophthalmic device according to any one of claims 1-35, comprising two or more types of PVOH and wherein two types of the PVOH differ in chain length by at least 1000, and have similar degrees of hydrolysis, both between 97% and 100%.

37. The ophthalmic device according to any one of claims 1-36, comprising two or more types of PVOH and wherein a first type of said two or more types has a hydrolysis degree from 97% to 100%.

38. The ophthalmic device according to claim 37, wherein a second type of said two or more types has a hydrolysis degree is lower than 93%.

39. The ophthalmic device according to any one of claims 1-38, comprising two or more types of PVOH and wherein a second type of said two or more types has a hydrolysis degree from 80 % to 93%.

40. The ophthalmic device according to any one of claims 1-39, comprising two or more types of PVOH and wherein a first type of said two or more types has chains with more than 2500 units.

41. The ophthalmic device according to any one of claims 1-40, comprising two or more types of PVOH and wherein a second type of said two or more types has chains with less than 1500 units.

42. The ophthalmic device according to any one of claims 1-41, comprising two or more types of PVOH and wherein a relation between a first type of PVOH and a second type of PVOH of said two or more types is from about 3:1 to about 1:3.

43. The ophthalmic device according to any one of claims 1-42, comprising two or more types of PVOH and wherein a first type of said two or more types has chains with more than 2500 units and hydrolysis degree of 97% to 100%, and a second type of said two or more types has chains with less than 1000 units and hydrolysis degree of 80% to 93%.

44. The ophthalmic device according to any one of claims 1-43, comprising two or more types of PVOH and wherein said second type of PVOH makes more than 50% of said PVOH.

45. The ophthalmic device according to any one of claims 1-44, comprising two or more types of PVOH and wherein said at least two types of PVOH determine rate of degradation of said ophthalmic device.

46. The ophthalmic device according to claim 45, wherein said rate of degradation comprises a rate by which a predetermined change in a predetermined mechanical property takes place in simulated tear fluid (STF).

47. The ophthalmic device according to any one of claims 1-46, wherein a combined mass content of said PVOH and said one or more organic plasticizers is at least 70 %wt of the total weight of the matrix excluding said water.

48. The ophthalmic device according to any one of claims 1-47, wherein said elastomeric matrix is characterized by substantially isotropic swelling when being immersed in simulated tear fluid and at room temperature for 5 minutes.

49. The ophthalmic device according to any one of claims 1-48, wherein said elastomeric matrix swells by less than 50 % by volume when immersed in simulated tear fluid for 5 minutes at room temperature.

50. The ophthalmic device according to any one of claims 1-49, wherein said water constitute less than 50 %wt of the total mass content of the matrix.

51. The ophthalmic device according to any one of claims 1-50, essentially devoid of covalent crosslinking.

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