Hybrid punctal plugs and methods of use thereof

Abstract

The disclosure provides punctal plugs and their method of use for treating ocular diseases or conditions, or symptoms thereof. The punctal plug described here comprises a polymer portion and a composite portion, where the polymer portion is configured to be inserted into a punctum of the eye. An exemplary composite portion of a punctal plug described here comprises at least one active agent, where the active agent is released towards the punctal opening of the eye.

Description

HYBRID PUNCTAL PLUGS AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 579,363, filed August 29, 2024, which is incorporated by reference herein in its entirety.FIELD OF THE DISCLOSURE

[0002] The present disclosure is generally directed to ophthalmologic occlusion devices and their methods of use, where the devices can be punctal plugs.BACKGROUND

[0003] Punctal plugs are commonly used for temporary and more permanent occlusion of the puncta in ophthalmological diseases or conditions, such as but not limited to, dry eyes. Although there are various commercially available punctal plug designs and materials that can successfully treat ophthalmological diseases or conditions, punctal plugs present several complications. For example, punctal plugs can get “lost” or migrate from the puncta openings into the lacrimal drainage system, irritate and damage the cornea, cause inflammation and infections, or result in discomfort for the wearer. Some solutions to minimize or address such complications include: permanent punctal cauterization, suturing punctal plugs at the desired location, dissolvable punctal plugs, surgery, and the like. Unfortunately, complications from available punctal plugs or even some solutions can lead to scarring and damage to the lacrimal drainage system. Other treatments of ophthalmological diseases or conditions include topical medications (such as antibiotic eye drops), which result in inefficient delivery of medication or the need for increased dosages or concentration of medication. Accordingly, there is a long felt need for a safe, non-toxic, and non-migratory ophthalmologic occlusion device and methods of treating ophthalmologic diseases or conditions, or symptoms thereof.SUMMARY

[0004] The present disclosure is directed to overcoming or ameliorating one or more of the complications or problems described here. At least one aspect of the disclosure provides a safe, nontoxic, and non-migratory ophthalmologic occlusion device, that can release active agents as needed, where the device is useful for treating ophthalmologic or ocular diseases or conditions, or symptoms thereof. In some aspects, the ophthalmologic occlusion device comprises a punctal plug, comprising, consisting essentially of, or consisting of: (a) a polymer portion (A), wherein the polymer portion comprises a dome (Al), wherein the dome (Al) comprises a cavity (A2), wherein the cavity comprises a cylindrical tunnel (A3) and a base opening at a distal end (A4), wherein the base opening has a diameter greater than a diameter of the cylindrical tunnel; and (b) a composite portion (B), wherein the composite portion comprises a head (Bl) connected to a shaft (B2) connected to a base at a distal end(B3), wherein the composite portion (b) is connected to the polymer portion (a), wherein the base (B3) and a portion of the shaft (B2) of the composite portion (b) are configured to insert into the cavity (A2) of the polymer portion (a), wherein the dimensions of the cavity (A2) is less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2).

[0005] In certain aspects, a method, comprises, consists essentially of, or consists of: inserting the punctal plug of the disclosure into a punctum of a subject in need thereof, wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, thereby treating the subject in need thereof suffering from the ocular disease or condition.

[0006] Other aspects provide a method, comprising, consisting essentially of, or consisting of: inserting the punctal plug of the disclosure into a punctum of a subject in need thereof, wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, wherein the polymer portion (A) comprises an impermeable material (or an essentially impermeable material); releasing the active agent from an exposed portion of the composite portion (B) towards the punctal opening, thereby treating the subject in need thereof suffering from the ocular disease or condition.

[0007] Further aspects and further embodiments of the disclosure described in the preceding paragraphs will become apparent from the following description, given by way of example and with reference to the accompanying drawings.BRIEF DESCRIPTION OF FIGURES

[0008] The foregoing and other features and advantages of the disclosure will be apparent from the following, more particular description of various embodiments of the disclosure, as illustrated in the accompanying figures.

[0009] FIGs. 1A-1C are illustrations of an exemplary polymer portion (A) or dome (Al) of the disclosure, where the polymer portion 100 comprises a cavity (A2), where the cavity comprises a cylindrical tunnel (A3) and a base opening (A4) at a distal end of the cylindrical tunnel. FIG. 1A shows the polymer portion (Al) and cavity (A2). FIG. IB provides an illustration of a cross-section of an exemplary polymer portion along the A-axis, exposing the cylindrical tunnel (A3) and base opening (A4). FIG. 1C provides an exemplary cross-section of the polymer portion.

[0010] FIGs. 2A-2C are illustrations of an exemplary composite portion 200 (B1-B3) of the disclosure, where the composite portion comprises a head (Bl) connected to a shaft (B2), which is connected to a base (B3) at a distal end of the shaft. FIG. 2A shows a side view of the exemplary composite portion comprising the head (Bl), shaft (B2), and base (B3). FIG. 2B provides an illustration of another view of an exemplary composite portion 200 with a tilted head (Bl) rotated 90 degrees around the Z-axis relative to FIG. 2A. FIG. 2C provides an exemplary cross-section of a composite portion 200 with a tilted head (Bl).

[0011] FIGs. 3A-3D are illustrations of an exemplary punctal plug 300 of the disclosure (hybrid punctal plug), where the punctal plug comprises a polymer portion (Al) and a composite portion (BIBS). FIG. 3A shows a side view of the exemplary punctal plug, where the composite portion comprising the head (Bl), shaft (B2), and base (B3) is inserted into the polymer portion (Al) via the cavity (A2), where a portion of the shaft (B2) is inserted in the cylindrical tunnel (A3) and the base (B3) is inserted in the base opening (A4). FIG. 3B provides an illustration of another view of the exemplary punctal plug rotated 90 degrees around the Z-axis relative to FIG. 3A with a Z-axis through the composite portion (B1-B2, shown) and polymer dome portion (Al). FIG. 3C provides a view of an exemplary cross-section of the punctal plug with a tilted head (Bl). FIG. 3D shows a view of the punctal plug with a tilted head (B 1).

[0012] FIGs. 4A-4E are illustrations of an exemplary punctal plug 400 of the disclosure, where the composite portion is inserted and / or connectively attached to the polymer portion, and the straight head (Bl) is ovoid in shape having a diameter that is less than that of the polymer portion (Al). FIG. 4A shows a top view the exemplary punctal plug, where the polymer portion or dome (Al) (e.g., 1.3 mm) is wider than the head (Bl) of the composite portion. FIGs. 4B-4C provide illustrations of different side views of the exemplary punctal plug rotated 90 degrees around the Z-axis relative to each other showing the composite portion with a non-tilted, straight head (Bl), where a portion of the shaft (B2) and base (B3) are inserted and / or connectively attached to the polymer portion (Al) via the cylindrical tunnel (A3) and base opening (A4, not shown). FIGs. 4D-4E show different views of the exemplary punctal plug 400 (FIG. 4A) of the disclosure.

[0013] FIGs. 5A-5E are illustrations of an exemplary punctal plug 500 of the disclosure, where the composite portion is inserted and / or connectively attached to the polymer portion, and the straight head (Bl) is ovoid in shape and has a diameter that is greater than that of the polymer portion (Al), at least in one direction. FIG. 5A shows a top view the exemplary punctal plug, where the non-tilted, straight head (Bl) of the composite portion (B) extends over the polymer portion (Al) in one direction, where, for example, the dome (Al) has a diameter of 1.1 mm. FIGs. 5B-5C provide illustrations of different side views of the exemplary punctal plug showing the composite portion (Bl), where a portion of the shaft (B2) and base (B3) are inserted and / or connectively attached to the polymer portion (Al) via the cylindrical tunnel (A3) and base opening (A4, not shown). FIGs. 5D-5E show different views of the exemplary punctal plug 500 (FIG. 5A) of the disclosure.

[0014] FIGs. 6A-6D provide different views of an exemplary punctal plug 600 of the disclosure.

[0015] FIGs. 7A-7D provide different views of an exemplary punctal plug 700 of the disclosure.DETAILED DESCRIPTION

[0016] Detailed embodiments of the present disclosure are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the disclosure that can beembodied in various forms. In addition, each of the examples given in connection with the various embodiments of the disclosure is intended to be illustrative, and not restrictive.

[0017] The punctal plugs of the disclosure address continuing challenges, specifically, retention of the punctal plug in the punctum of an eye. Furthermore, the punctal plugs of the disclosure address a common complaint of other commonly used punctal plugs, namely discomfort or irritation. Another challenge that the punctal plugs of the disclosure address is directed or inefficient delivery of an active agent, for example, to the punctal openings instead of the lacrimal canaliculi, lacrimal sacs, or nasolacrimal ducts (or tear ducts).Punctal Plugs

[0018] In some embodiments, the design of the punctal plug described here enables better and longer retention within a punctum of a subject in need thereof, as compared to punctal plugs having a different design or structure as described here, z.e., 2 weeks or longer (e.g., 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30); 24 weeks (6 months) or less (e.g., 23, 21, 19, 17, 15, 13, 11, 9, 7, 5, 3, 1); 2 weeks - 24 weeks (e.g., 3 weeks - 23 weeks; 4 weeks - 22 weeks; 5 weeks - 21 weeks; 6 weeks - 20 weeks; 7 weeks - 19 weeks; 8 weeks - 18 weeks; 9 weeks - 17 weeks; 10 weeks - 16 weeks; 11 weeks - 15 weeks; 12 weeks - 14 weeks), as well as, when comprising, consisting essentially of, or consisting of at least one active agent, efficient active agent release. The active agent optionally incorporated in the composite portion (B) of the punctal plug allows for an improved release profile compared to the same active agent released from a different punctal plug without the design or materials used for the disclosed punctal plug. Without wishing to be bound by theory, the impermeable polymer portion (A) prevents any or most active agent from the inserted composite portion (B) from being released from or through the polymer portion (A) or dome (Al). Instead, the active agent is directed towards the head (Bl) of the permeable composite portion (B), which is made of a different material than the impermeable polymer portion (A), such that there is less or minimal active agent loss and a reduction of any adverse burst effect of active agent. In other embodiments, the punctal plug of the disclosure comprises a coating, where the coating covers a portion or an outer surface of the punctal plug. The coating can be on the outer surface of the polymer portion (A) or dome (Al) and / or the outer surface of the composite portion (B). The optional coating can be on the entire or partial outer surface of the punctal plug, where the coating is complete, continuous, or perforated. In some aspects, the coating, if used, can be composed of a chemically inert, conformable, flaking resistant, physiologically acceptable material. For example, the coating can comprise butvar and / or parylene. An exemplary butvar or parylene coating can have a thickness measuring 2 micrometers (pm) or greater (e.g., 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.05, 5.1, 5.15, 5.2, 5.25, 5.3, 5.35, 5.4, 5.45, 5.5); 5 micrometers or less (e.g., 4.95, 4.85, 4.75, 4.65, 4.55, 4.45, 4.35, 4.25, 4.15, 4.05, 3.95, 3.85, 3.75, 3.65, 3.55, 3.45, 3.35, 3.25, 3.15, 3.05, 2.95, 2.85, 2.75, 2.65, 2.55, 2.45, 2.35, 2.25, 2.15, 2.05, 1.95, 1.85, 1.75, 1.65, 1.55, 1.45, 1.35, 1.25, 1.15, 1.05); or arange of 2 gm - 5 gm (e.g., 2.05 gm - 4.95 gm; 2.1 gm - 4.9 gm; 2.15 gm - 4.85 gm; 2.2 gm - 4.8 gm;2.25 gm - 4.75 gm; 2.3 gm - 4.7 gm; 2.35 gm - 4.65 gm; 2.4 gm - 4.6 gm; 2.45 gm - 4.55 gm; 2.5 gm - 4.5 gm; 2.55 gm - 4.45 gm; 2.6 gm - 4.4 gm; 2.65 gm - 4.35 gm; 2.7 gm - 4.3 gm; 2.75 gm -4.25 gm; 2.8 gm - 4.2 gm; 2.85 gm - 4.15 gm; 2.9 gm - 4.1 gm; 2.95 gm - 4.05 gm; 3 gm - 4 gm; 3.05 gm - 3.95 gm; 3.1 gm - 3.9 gm; 3.15 gm - 3.85 gm; 3.2 - 3.8 gm; 3.25 gm - 3.75 gm; 3.3 gm - 3.7 gm; 3.35 gm - 3.65 gm; 3.4 gm - 3.6 gm; 3.45 gm -3.55 gm). Various details of these optional features are described in U.S. Pat. No. 10,471,090 and U.S. Pub. No. 2020 / 0147055, which are incorporated by reference herein in their entirety for all purposes, including but not limited to coatings and materials for use with the punctal plugs of the disclosure. Some embodiments provide for a punctal plug that enables a constant, linear, controlled release of active agent, which has a duration of months, and allows for the punctal plug to remain comfortably in the punctum of a subject in need thereof for months. Various aspects of the punctal plug described here allows for any size or dimensions, with the only limitation being anatomical. The punctal plug of the disclosure can be formulated to have dimensions appropriate for a wide or a narrow punctal opening of a subject in need. Moreover, the flexible, chemically inert material of the polymer portion (A) enables conformity to the punctum and reduces any adverse tissue response, which can stimulate tissue edema or fluid buildup, thereby exerting a force such that the plug is displaced from the punctum. In some embodiments, the punctal plug of the disclosure does not comprise or lacks a reservoir or a chamber for holding tears or active agents. Some subjects in need of a punctal plug can require a wide or a narrow diameter of the polymer portion (A) or dome (Al), a longer or shorter height or length of the shaft (B2) of the composite portion (B), and diameter or angle of the head (B 1) in order to have a comfortable fit, without irritation, and retention in the punctum. An angled or tilted head (Bl) compared to a vertical shaft (B2) allows the punctal plug to conform to an eyelid’s natural slope, such that the head is flush to the punctum opening and is anatomically determined. The head (Bl) can be any shape that is conducive for a proper fit and comfort, such as but not limited to a circle, an oval, an ellipse, an oblong, or an egg shape, where the head can be straight or flat (z.e., at a 90° angle compared to the vertical shaft (B2)) or tilted at an angle greater than or less than 90° compared to the vertical shaft. Additional aspects provide for the straight or tilted head punctal plugs described here having the same diameter ratio of head to dome. For example, if the straight head punctal plug has a 1 : 1 diameter ratio of head to dome, then the tilted head punctal plug can have the same 1: 1 diameter ratio of head to dome. Non-limiting examples of diameter ratios of head to dome (head:dome) include 1:50 or greater (e.g., 1:40, 1:30, 1:20, 1: 10, 2: 19, 1:9, 2: 17, 1:8, 2: 15, 1:7, 2: 13, 1:6, 2: 11, 1:5, 2:9, 1:4, 2:7, 1:3, 2:5, 1:2, 2:3, 1: 1, 3:2, 2: 1, 5:2, 3: 1, 7:2, 4: 1, 9:2, 5: 1, 11:2, 6: 1, 13:2, 7: 1, 15:2, 8: 1, 17:2, 9: 1, 19:2, 10: 1, 11: 1, 12: 1, 13: 1, 14: 1, 15: 1, 25: 1, 35: 1, 45: 1, 55: 1); 50: 1 or less (e.g., 45: 1, 35: 1, 25: 1, 15: 1, 14: 1, 13: 1, 12: 1, 11: 1, 10: 1, 19:2, 9: 1; 17:2, 8: 1, 15:2, 7: 1, 13:2, 6: 1, 11:2, 5: 1, 9:2, 4: 1, 7:2, 3: 1, 5:2, 2: 1, 3:2, 1: 1, 2:3, 1:2, 2:5, 1:3, 2:7, 1:4, 2:9, 1:5, 2: 11, 1:6, 2: 13, 1:7, 2: 15, 1:8, 2: 17, 1:9, 2: 19, 1: 10, 1:20, 1:50, 1:60); or 1:50 to 55: 1 (e.g., 1:40 to 45: 1, 1:30 to 35: 1, 1:20 to 25: 1, 1: 10 to 15: 1, 2: 19 to 14: 1, 1:9 to 13: 1, 2: 17 to 12: 1, 1:8 to 11: 1, 2: 15 to 10: 1, 1:7 to 19:2, 2: 13to 9: 1, l:6 to 17:2, 2: 11 to 8: 1, 1:5 to 15:2, 2:9 to 7: 1, 1:4 to 13:2, 2:7 to 6: 1, 1:3 to 11:2, 2:5 to 5: 1, 1:2 to 9:2, 2:3 to 4: 1, 1: 1 to 7:2, 3:2 to 3: 1, 2: 1 to 5:2). Some aspects of the punctal plug disclosed here incorporate a dome (Al) that has a flat bottom or a rounded shape, which can aid in the insertion, retention, or comfort of the punctal plug in the punctum of a subject. Moreover, the materials used in the punctal plug of the disclosure are soft and flexible, where the dual or hybrid punctal plug provides different specific materials for the polymer portion (A) or dome (Al) and the composite portion (B).

[0019] Additional embodiments of the disclosure provide a punctal plug or a hybrid punctal plug, where the punctal plug comprises a polymer portion (A: A1-A4) and a composite portion (B: B1-B3), where the composite portion is inserted and / or connectively attached to the polymer portion. The polymer portion comprises a soft, flexible polymer, where the polymer portion (A) comprises a dome (Al) for insertion into a punctum of an eye of a subject. The dome (Al) of the polymer portion (A) can in some embodiments have a flat bottom or a rounded bottom, where in some instances, the rounded bottom can provide easier insertion into the punctum of the eye of a subject than with the flat bottom dome (Al). The soft, flexible polymer of the polymer portion (A) of the punctal plug of the disclosure is configured for superior retention in the punctum, where the polymer comprises a chemically inert, physiologically acceptable material, such as but not limited to, silicone, silicone-based polymer, polyacrylate, polyurethane, and combinations / blends thereof (e.g., liquid silicone rubber, such as NUSIL MED-4840 / -4850 / -4860 / -4870 / -4880; polyurethane rubber such as POLYTEK PT Flex 50 / 60 / 70 / 85; polyacrylate acrylic rubber; where the material has a hardness range of Shore A 40-90, such as Robinson Rubber Products). Additional aspects provide the polymer portion comprising a medical grade silicone or medical grand silicone-based polymer. In some aspects, the polymer portion (A) comprises an impermeable material or an essentially impermeable material, where, for example, an active agent or other small molecule cannot permeate or essentially cannot permeate through the impermeable material of the polymer portion (A) or dome (Al). The polymer portion (A) or dome (Al) is of a material that does not comprise an active agent.

[0020] Further embodiments provide the polymer portion (A) of the punctal plug of the disclosure, where the polymer portion comprising a dome (Al) further comprises a cavity (A2) (or elongated cavity). The cavity comprises a cylindrical tunnel (A3) and a base opening (A4) at a distal end of the cylindrical tunnel. The base opening comprises a diameter that is greater than a diameter of the cylindrical tunnel. In some aspects, the dimensions of the cavity (A2) are less than the dimensions of the composite portion (B), for example, the cylindrical tunnel (A3) initially has a diameter that is less than the shaft (B2) and the base opening (A4) initially has a diameter than is less than the base (B3). However, during, for example, manufacture or when the composite portion (B) is inserted or connectively attached to the polymer portion (A), the flexible material of the polymer portion (e.g., silicone, silicone -based polymer, polyacrylate, polyurethane, and combinations / blends thereof) allows for the cylindrical tunnel (A3) and the base opening (A4) to expand, thereby accommodating thedimensions of the shaft (B2) and base (B3), respectively, when the composite portion (B) is inserted in the polymer portion (A), such that the polymer portion (A) or dome (Al) and the composite portion (B) are tightly fitted.

[0021] In some embodiments, the composite portion (B) and the polymer portion (A) or dome (Al) that form the punctal plug or hybrid punctal plug of the disclosure are secured together, where the composite portion is inserted into the polymer portion or dome, with or without the use of a biocompatible glue. Non-limiting examples of biocompatible glues include fibrin glue, an epoxy resin or adhesive (e.g., EPO-TEK® MED-301 (Epoxy Technology; Billerica, Massachusetts, USA)), medical grade cyanoacrylate (e.g., DERMABOND® (2 -octylcyanoacrylate); Ethicon, Inc.; Raritan, New Jersey, USA), medical grade silicone adhesive (e.g., MED-2000; Avantor® Inc.; Radnor, Pennsylvania, USA), or combinations thereof, in an amount sufficient to secure the composite portion (B) and the polymer portion (A) or dome (Al), specifically the composite portion (B) into the polymer portion (A) or dome (Al). Other aspects for securing the composite portion (B) and the polymer portion (A) or dome (Al) include using a small quantity of the biocompatible glue that is either injected into the polymer cavity (A2) or the dome (Al) using a syringe with, for example, a 27G needle, and / or applying the biocompatible glue on the distal portion of the composite shaft (B2) and / or on the composite base (B3), where application can be by any means, such as but not limited to, spreading, dipping, or both. In further aspects, after the composite portion and the polymer portion or dome are secured, the biocompatible adhesive is allowed to dry for several hours (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) sufficient for completely drying the adhesive and securing the composite and polymer portions to form the punctal plug of the disclosure. Some aspects include an amount of biocompatible glue that is 20 micrograms (pg) or greater (e.g., 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150); 100 micrograms (pg) or less (e.g., 99, 97, 95, 93, 91, 89, 87, 85, 83, 81, 75, 65, 55, 45, 35, 25, 15, 5); or 20 micrograms (pg) - 100 micrograms (pg) (e.g., 21 pg - 99 pg; 22 pg - 98 pg; 23 pg - 97 pg; 24 pg - 96 pg; 25 pg - 95 pg; 26 pg - 94 pg; 27 pg - 93 pg; 28 pg - 92 pg; 29 pg - 91 pg; 30 pg - 90 pg; 31 pg - 89 pg; 32 pg - 88 pg; 33 pg - 87 pg; 34 pg - 86 pg; 35 pg - 85 pg;36 pg - 84 pg; 37 pg - 83 pg; 38 pg - 82 pg; 39 pg - 81 pg; 40 pg - 80 pg; 41 pg - 79 pg; 42 pg - 78 pg; 43 pg - 77 pg; 44 pg - 76 pg; 45 pg - 75 pg; 46 pg - 74 pg; 47 pg - 73 pg; 48 pg - 72 pg; 49 pg -71 pg; 50 pg - 70 pg; 51 pg - 69 pg; 52 pg - 68 pg; 53 pg - 67 pg; 54 pg - 66 pg; 55 pg - 65 pg; 56 pg - 64 pg; 57 pg - 63 pg; 58 pg - 62 pg; 59 pg - 61 pg).

[0022] To illustrate these concepts with greater specificity, the figures are presented and meant to be instructive, but not exhaustive of the possible structure and materials of the exemplary embodiments of the present disclosure, where in some instances, similar reference numerals refer to similar structures.

[0023] An exemplary polymer portion (A) of a punctal plug or a hybrid punctal plug described here is shown in FIG. 1. Shown is a polymer portion 100 having a flat-bottom dome (Al) (FIGs. 1A-1B) configured for insertion, retention, and / or comfort of the device or punctal plug into a punctum of asubject. In instances where the polymer portion (A) or dome (Al) comprises a flat bottom dome shape, the flat bottom comprises a diameter or a length 140 of 0.1 mm or greater (e.g., 0.3; 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.1 mm - 2 mm (e.g., 0.2 mm - 1.9 mm; 0.3 mm - 1.8 mm; 0.4 mm - 1.7 mm; 0.5 mm - 1.6 mm; 0.6 mm - 1.5 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm). The polymer portion 100 of the punctal plug has a cavity (A2) for housing a composite portion (B) of the punctal plug. FIGs. 1B-1C show the cylindrical tunnel (A3) and the base opening (A4) at the distal end of the cylindrical tunnel. The diameter of the dome (Al) 105 is configured to fit a subject’s punctum and can vary in length depending on the size of the subject’s punctum. In some embodiments, the diameter of the polymer portion (A) or dome (Al) at its widest point, typically at the opening of the cavity (A2), is 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm). Other aspects provide a diameter 105 of the polymer portion (A) or dome (Al) in a range of 0.9 mm - 1.35 mm, where a punctal plug of the disclosure comprises a polymer portion having a diameter that appropriately fits a narrow nose or a wider nose. FIGs. 1B-1C illustrate that the base opening (A4) has a diameter 110 that is wider than the cylindrical tunnel (A3) diameter 115. Some embodiments provide for a base opening (A4) having a diameter 110 of 0.3 mm or greater (e.g., 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9; 2.1; 2.3; 2.5); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.3 mm - 2 mm (e.g., 0.4 mm - 1.9 mm; 0.5 mm - 1.8 mm; 0.6 mm - 1.7 mm; 0.7 mm - 1.6 mm; 0.8 mm - 1.5 mm; 0.9 mm - 1.4 mm; 1 mm - 1.3 mm; 1.1 mm - 1.2 mm). In other embodiments, the cylindrical tunnel (A3) has a smaller diameter 115 than that of the base opening (A4), where the cylindrical tunnel (A3) comprises a diameter 115 of 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.1 mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm - 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm).

[0024] Further embodiments provide a polymer portion (A) of the disclosure, comprising various heights of the dome (Al), cylindrical tunnel (A3), and base opening (A4), where the height of the polymer portion (A) or dome (Al) is typically greater than the height of the cylindrical tunnel (A3),which is greater than the height of the base opening (A4). FIG. 1C shows the height 120 of the cylindrical tunnel (A3), which can be 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); oe.g. l mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm - 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm). The height 125 of the base opening (A4) comprises 0.05 mm or greater (e.g., 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5); 2 mm or less (e.g., 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.05 mm - 2 mm (e.g., 0.1 mm - 1.95 mm; 0.15 mm - 1.9 mm; 0.2 mm - 1.85 mm; 0.25 mm - 1.8 mm; 0.3 mm - 1.75 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm). While, in some embodiments, the height 130 of the dome (Al) is greater than both the height 120 of the cylindrical tunnel (A3) and the height 125 of the base opening (A4), where the polymer portion (A) or dome (Al) comprises a height 130 of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm -2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm).

[0025] In some embodiments, a polymer portion (A) or dome (Al) of a punctal plug of the disclosure can comprise a flat bottom having a length 140 of 0.1 mm or greater (e.g., 0.3; 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.1 mm - 2 mm (e.g., 0.2 mm - 1.9 mm; 0.3 mm - 1.8 mm; 0.4 mm - 1.7 mm; 0.5 mm - 1.6 mm; 0.6 mm - 1.5 mm; 0.7 mm -1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm), where the length 140 is typically less than the diameter 115 of the cylindrical tunnel (A3), which is typically less than a diameter 110 of the base opening (A4), which is typically less than a diameter 105 of the polymer portion (A) or dome (Al).

[0026] FIG. 1C also shows 150, which is the radius, for example, 0.05 mm, of the base opening (A4); 160, which is the radius, for example, 0.4 mm - 0.5 mm, of a curvature of the dome (Al) where indicated; and 170, which is the radius, for example, 1 mm, of a curvature of the dome (Al) where indicated.

[0027] In some embodiments of the disclosure, where the composite portion (B), which is inserted and / or connectively attached to the polymer portion (A), together form a punctal plug of the disclosure.The composite portion (B) comprises a head (Bl) connectively attached to a shaft (B2), which is connectively attached to a base (B3). The head (Bl) of the composite portion (B) of the disclosed punctal plug or hybrid punctal plug can be essentially perpendicular or perpendicular to the shaft (B2). Other aspects provide for a head (Bl) that is positioned at an angle as compared to the shaft (B2), where the straight portion of the head (Bl) is compared to a vertical axis through the shaft (B2) to form the angle. In one aspect, the composite portion (B) of the punctal plug or hybrid punctal plug disclosed here comprises a binder; an absorbent material; and optionally, an active agent or a combination of active agents. Some aspects provide a composite portion (B) of the punctal plug or hybrid punctal plug described here that does not contain an active agent or combination of active agents. In some instances, the binder comprises epoxy; the absorbent material comprises fumed silica, hydroxypropyl methylcellulose (HPMC)-based polymer, or any combinations or blends thereof; and the active agent or combinations thereof is an ophthalmological active agent, which includes those that are used to treat an ocular disease or condition in a subject in need thereof, where treatment includes administration of an active agent to the surface of the eye or via tissues surrounding the eye and / or administration of a punctal plug for blocking tear drainage from the eye. The punctal plug of the disclosure can be administered or inserted into the puncta (upper and / or lower) of a subject suffering from an ocular disease or condition. Non-limiting active agents for use in the punctal plug or hybrid punctal plug of the disclosure include: prostaglandin analogs (e.g., bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod); antibiotics (e.g., fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline); macrolides (e.g., 12-membered (e.g., methymycin); 14-membered (e.g., clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin); 15-membered (e.g., azithromycin); 16-membered (e.g., miokamycin, rokitamycin, tilmicosin); ketolides (e.g., telithromycin, cethromycin, solithromycin)); immunosupressants (e.g., tacrolimus, pimecrolimus, sirolimus, cyclosporine), corticosteroids (e.g., dexamethasone; ceftazidime)); beta-blockers (e.g., timolol, levobunolol, metipranolol, carteolol); antifungals (e.g. polyenes, azoles, allylamines, echinocandins); antihistamines (e.g., cetirizine, desloratadine, diphenhydramine, epinastine, fexofenadine, ketotifen, levocetirizine, olopatadine); antiinflammatory agents (e.g., ketorolac, loteprednol); tear lubricants (e.g., hydroxypropyl cellulose); and tear producers (e.g., cholinergics (e.g., pilocarpine, cevimeline)); or any combinations thereof. In some aspects of the disclosure, the composite portion (B) comprises an active agent selected from the group consisting of: bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod; fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline; methymycin; clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin; azithromycin; miokamycin, rokitamycin, tilmicosin; telithromycin, cethromycin, solithromycin; tacrolimus, pimecrolimus, sirolimus, cyclosporine; dexamethasone; ceftazidime; hydroxypropyl cellulose; pilocarpine, cevimeline; tacrolimus; and any combinations thereof. The concentration of an active agent in the composite portion (B) of the disclosure can bepresent in varying concentrations depending on the desired release of active agent. For example, the active agent can have a concentration of 0.05 mg / ml or more (e.g., 0.15; 0.25; 0.35; 0.45; 0.55; 0.65; 0.75; 0.85; 0.95; 1.05; 1.15; 1.25; 1.35; 1.45; 1.55; 1.65; 1.75; 1.85; 1.95; 2.05; 2.15; 2.25; 2.35; 2.45;2.55; 2.65; 2.75; 2.85; 2.95; 3.05; 3.15; 3.25; 3.35; 3.45; 3.55; 3.65; 3.75; 3.85; 3.95; 4.05; 4.15; 4.25;4.35; 4.45; 4.55; 4.65; 4.75; 4.85; 4.95; 5.05; 5.15; 5.25; 5.35; 5.45; 5.55; 5.65; 5.75; 5.85; 5.95; 6.05;6.15; 6.25; 6.35; 6.45; 6.55; 6.65; 6.75; 6.85; 6.95; 7.05; 7.15; 7.25; 7.35; 7.45; 7.55; 7.65; 7.75; 7.85;7.95; 8.05; 8.15; 8.25; 8.35; 8.45; 8.55; 8.65; 8.75; 8.85; 8.95; 9.05; 9.15; 9.25; 9.35; 9.45; 9.55; 9.65;9.75; 9.85; 9.95; 10.05; 10.15; 10.25; 10.35; 10.45; 10.55; 10.65; 10.75; 10.85; 10.95; 11.05; 11.15; 11.25; 11.35; 11.45; 11.55; 11.65; 11.75; 11.85; 11.95; 12.05; 12.15; 12.25; 12.35; 12.45; 12.55; 12.65; 12.75; 12.85; 12.95; 13.05; 13.15; 13.25; 13.35; 13.45; 13.55; 13.65; 13.75; 13.85; 13.95; 14.05; 14.15; 14.25; 14.35; 14.45; 14.55; 14.65; 14.75; 14.85; 14.95; 15.05; 15.15; 15.25; 15.35; 15.45; 15.55); 15 mg / ml or less (e.g., 14.9; 14.8; 14.7; 14.6; 14.5; 14.4; 14.3; 14.2; 14.1; 14; 13.9; 13.8; 13.7; 13.6; 13.5; 13.4; 13.3; 13.2; 13.1; 13; 12.9; 12.8; 12.7; 12.6; 12.5; 12.4; 12.3; 12.2; 12.1; 12; 11.9; 11.8; 11.7; 11.6; 11.5; 11.4; 11.3; 11.2; 11.1; 11; 10.9; 10.8; 10.7; 10.6; 10.5; 10.4; 10.3; 10.2; 10.1; 10; 9.9; 9.8; 9.7;9.6; 9.5; 9.4; 9.3; 9.2; 9.1; 9; 8.9; 8.8; 8.7; 8.6; 8.5; 8.4; 8.3; 8.2; 8.1; 8; 7.9; 7.8; 7.7; 7.6; 7.5; 7.4; 7.3;7.2; 7.1; 7; 6.9; 6.8; 6.7; 6.6; 6.5; 6.4; 6.3; 6.2; 6.1; 6; 5.9; 5.8; 5.7; 5.6; 5.5; 5.4; 5.3; 5.2; 5.1; 5; 4.9; 4.8; 4.7; 4.6; 4.5; 4.4; 4.3; 4.2; 4.1; 4; 3.9; 3.8; 3.7; 3.6; 3.5; 3.4; 3.3; 3.2; 3.1; 3; 2.9; 2.8; 2.7; 2.6; 2.5;2.4; 2.3; 2.2; 2.1; 2; 1.9; 1.8; 1.7; 1.6; 1.5; 1.4; 1.3; 1.2; 1.1; 1; 0.9; 0.8; 0.7; 0.6; 0.5; 0.4; 0.3; 0.2; 0.1;0.09; 0.08; 0.07; 0.06; 0.05; 0.04; 0.03; 0.02; 0.01; 0.009; 0.008; 0.007; 0.006; 0.005; 0.004; 0.003; 0.002; 0.001); 0.05 mg / ml - 15 mg / ml (e.g., 0.06 mg / ml - 14.95 mg / ml; 0.07 mg / ml - 14.9 mg / ml; 0.08 mg / ml - 14.85; 0.09 mg / ml - 14.8 mg / ml; 0.1 mg / ml - 14.75 mg / ml; 0.15 mg / ml - 14.7 mg / ml; 0.2 mg / ml - 14.65 mg / ml; 0.25 mg / ml - 14.6 mg / ml; 0.3 mg / ml - 14.55 mg / ml; 0.35 mg / ml - 14.5 mg / ml; 0.4 mg / ml - 14.45 mg / ml; 0.45 mg / ml - 14.4 mg / ml; 0.5 mg / ml - 14.35 mg / ml; 0.55 mg / ml - 14.3 mg / ml; 0.6 mg / ml - 14.25 mg / ml; 0.65 mg / ml - 14.2 mg / ml; 0.7 mg / ml - 14.15 mg / ml; 0.75 mg / ml - 14.1 mg / ml; 0.8 mg / ml - 14.05 mg / ml; 0.85 mg / ml - 14 mg / ml; 0.9 mg / ml - 13.95 mg / ml; 0.95 mg / ml- 13.9 mg / ml; I mg / ml - 13.85 mg / ml; 1.05 mg / ml - 13.8 mg / ml; l. l mg / ml - 13.75 mg / ml; 1.15 mg / ml- 13.7 mg / ml; 1.2 mg / ml - 13.65 mg / ml; 1.25 mg / ml - 13.6 mg / ml; 1.3 mg / ml - 13.55 mg / ml; 1.35 mg / ml - 13.5 mg / ml; 1.4 mg / ml - 13.45 mg / ml; 1.45 mg / ml - 13.4 mg / ml; 1.5 mg / ml - 13.35 mg / ml;I.55 mg / ml - 13.3 mg / ml; 1.6 mg / ml - 13.25 mg / ml; 1.65 mg / ml - 13.2 mg / ml; 1.7 mg / ml - 13.15 mg / ml; 1.75 mg / ml - 13.1 mg / ml; 1.8 mg / ml - 13.05 mg / ml; 1.85 mg / ml - 13 mg / ml; 1.9 mg / ml - 12.95 mg / ml; 1.95 mg / ml - 12.9 mg / ml; 2 mg / ml - 12.85 mg / ml; 2.05 mg / ml - 12.8 mg / ml; 2.1 mg / ml- 12.75 mg / ml; 2.15 mg / ml - 12.7 mg / ml; 2.2 mg / ml - 12.65 mg / ml; 2.25 mg / ml - 12.6 mg / ml; 2.3 mg / ml - 12.55 mg / ml; 2.35 mg / ml - 12.5 mg / ml; 2.4 mg / ml - 12.45 mg / ml; 2.45 mg / ml - 12.4 mg / ml; 2.5 mg / ml - 12.35 mg / ml; 2.55 mg / ml - 12.3 mg / ml; 2.6 mg / ml - 12.25 mg / ml; 2.65 mg / ml - 12.2 mg / ml; 2.7 mg / ml - 12.15 mg / ml; 2.75 mg / ml - 12.1 mg / ml; 2.8 mg / ml - 12.05 mg / ml; 2.85 mg / ml - 12 mg / ml; 2.9 mg / ml - 11.95 mg / ml; 2.95 mg / ml - 11.9 mg / ml; 3 mg / ml - 11.85 mg / ml; 3.05 mg / ml -I I.8 mg / ml; 3.1 mg / ml - 11.75 mg / ml; 3.15 mg / ml - 11.7 mg / ml; 3.2 mg / ml - 11.65 mg / ml; 3.25 mg / ml- 11.6 mg / ml; 3.3 mg / ml - 11.55 mg / ml; 3.35 mg / ml - 11.5 mg / ml; 3.4 mg / ml - 11.45 mg / ml; 3.45 mg / ml - 11.4 mg / ml; 3.5 mg / ml - 11.35 mg / ml; 3.55 mg / ml - 11.3 mg / ml; 3.6 mg / ml - 11.25 mg / ml;3.65 mg / ml - 11.2 mg / ml; 3.7 mg / ml - 11.15 mg / ml; 3.75 mg / ml - 11.1 mg / ml; 3.8 mg / ml - 11.05 mg / ml; 3.85 mg / ml - 11 mg / ml; 3.9 mg / ml - 10.95 mg / ml; 3.95 mg / ml - 10.9 mg / ml; 4 mg / ml - 10.85 mg / ml; 4.05 mg / ml - 10.8 mg / ml; 4.1 mg / ml - 10.75 mg / ml; 4.15 mg / ml - 10.7 mg / ml; 4.2 mg / ml -10.65 mg / ml; 4.25 mg / ml - 10.6 mg / ml; 4.3 mg / ml - 10.55 mg / ml; 4.35 mg / ml - 10.5 mg / ml; 4.4 mg / ml- 10.45 mg / ml; 4.45 mg / ml - 10.4 mg / ml; 4.5 mg / ml - 10.35 mg / ml; 4.55 mg / ml - 10.3 mg / ml; 4.6 mg / ml - 10.25 mg / ml; 4.65 mg / ml - 10.2 mg / ml; 4.7 mg / ml - 10.15 mg / ml; 4.75 mg / ml - 10.1 mg / ml; 4.8 mg / ml - 10.05 mg / ml; 4.85 mg / ml - 10 mg / ml; 4.9 mg / ml - 9.95 mg / ml; 4.95 mg / ml - 9.9 mg / ml; 5 mg / ml - 9.85 mg / ml; 5.05 mg / ml - 9.8 mg / ml; 5.1 mg / ml - 9.75 mg / ml; 5.15 mg / ml - 9.7 mg / ml; 5.2 mg / ml - 9.65 mg / ml; 5.25 mg / ml - 9.6 mg / ml; 5.3 mg / ml - 9.55 mg / ml; 5.35 mg / ml - 9.5 mg / ml; 5.4 mg / ml - 9.45 mg / ml; 5.45 mg / ml - 9.4 mg / ml; 5.5 mg / ml - 9.35 mg / ml; 5.55 mg / ml - 9.3 mg / ml; 5.6 mg / ml - 9.25 mg / ml; 5.65 mg / ml - 9.2 mg / ml; 5.7 mg / ml - 9.15 mg / ml; 5.75 mg / ml - 9.1 mg / ml; 5.8 mg / ml - 9.05 mg / ml; 5.85 mg / ml - 9 mg / ml; 5.9 mg / ml - 8.95 mg / ml; 5.95 mg / ml - 8.9 mg / ml; 6 mg / ml - 8.85 mg / ml; 6.05 mg / ml - 8.8 mg / ml; 6.1 mg / ml - 8.75 mg / ml; 6.15 mg / ml - 8.7 mg / ml; 6.2 mg / ml - 8.65 mg / ml; 6.25 mg / ml - 8.6 mg / ml; 6.3 mg / ml - 8.55 mg / ml; 6.35 mg / ml - 8.5 mg / ml; 6.4 mg / ml - 8.45 mg / ml; 6.45 mg / ml - 8.4 mg / ml; 6.5 mg / ml - 8.35 mg / ml; 6.55 mg / ml - 8.3 mg / ml; 6.6 mg / ml - 8.25 mg / ml; 6.65 mg / ml - 8.2 mg / ml; 6.7 mg / ml - 8.15 mg / ml; 6.75 mg / ml - 8.1 mg / ml; 6.8 mg / ml - 8.05 mg / ml; 6.85 mg / ml - 8 mg / ml; 6.9 mg / ml - 7.95 mg / ml; 6.95 mg / ml - 7.9 mg / ml; 7 mg / ml - 7.85 mg / ml; 7.05 mg / ml - 7.8 mg / ml; 7.1 mg / ml - 7.75 mg / ml; 7.15 mg / ml - 7.7 mg / ml; 7.2 mg / ml - 7.65 mg / ml; 7.25 mg / ml - 7.6 mg / ml; 7.3 mg / ml - 7.55 mg / ml; 7.35 mg / ml - 7.5 mg / ml; 7.4 mg / ml - 7.45 mg / ml), although smaller or greater concentrations may potentially be used, up to the limit of solubility of the active agent. A person of ordinary skill in the art would understand how to design the punctal plug, more specifically, the composite portion (B), of the disclosure to release a desired amount or concentration of active agent to the subject in need thereof. Moreover, the administration of an ophthalmological active agent in the punctal plug of the disclosure can be determined as a function of the subject’s age, weight, gender, eye surface area, or other factors, active agent release profile, or combinations thereof, as determined by a medical practitioner, formulator, or device engineer.

[0028] An exemplary composite portion (B) of a punctal plug or a hybrid punctal plug described here is shown in FIGs. 2A-2C. In some embodiments, the head (Bl) can be tilted or essentially perpendicular compared to the shaft (B2). A tilted head (Bl) can provide a better position in the punctum as well as with respect to a subject’s eyelid, allowing for the head of the punctal plug to be flush with the natural slope of the eyelid when inserted in the punctum and for comfort. Shown is a composite portion (B) having a head (Bl), which is tilted as compared to the shaft (B2), where the head (Bl) is positioned at an angle 240 comprising 90° or greater (e.g., 91; 92; 93; 94; 95; 96; 97; 98; 99;100; 101; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125); 120.5° or less (e.g., 119.5; 118.5; 117.5; 116.5; 115.5; 114.5; 113.5; 112.5; 111.5; 110.5; 109.5; 108.5; 107.5; 106.5; 105.5; 104.5; 103.5; 102.5; 101.5; 100.5; 99.5; 98.5; 97.5; 96.5; 95.5; 94.5; 93.5; 92.5; 91.5; 90.5; 89.5; 88.5; 87.5; 86.5; 85.5); or 90° - 120.5° (e.g., 90.5°- 120°; 91° - 119.5°; 91.5° - 119°; 92° - 118.5°; 92.5° - 118°; 93° - 117.5°; 93.5° - 117°; 94° - 116.5°; 94.5° - 116°; 95° - 115.5°; 95.5° - 115°; 96° - 114.5°; 96.5° - 114°; 97° - 113.5°; 97.5° - 113°; 98° - 112.5°; 98.5° - 112°; 99° - 111.5°; 99.5° - 111°; 100° - 110.5°; 101.5° - 110°; 102° - 109.5°; 102.5°- 109°; 103° - 108.5°; 103.5° - 108°; 104° - 107.5°; 104.5° - 107°; 105° - 106.5°; 105.5° - 106°).

[0029] FIGs. 2A-2C show a composite portion (B) 200 comprising a tilted head (Bl) connectively attached to a shaft (B2), which is connectively attached to a base (B3). FIG. 2C shows the diameter 205 of the head (Bl), which can be 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4); 2.5 or less (e.g., 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15); or 0.5 mm- 2.5 mm (e.g., 0.55 mm - 2.45 mm; 0.6 mm - 2.4 mm; 0.65 mm - 2.35 mm; 0.7 mm - 2.3 mm; 0.75 mm - 2.25 mm; 0.8 mm - 2.2 mm; 0.85 mm - 2.15 mm; 0.9 mm - 2.1 mm; 0.95 mm - 2.05 mm; 1 mm- 2 mm; 1.05 mm - 1.95 mm; 1.1 mm - 1.9 mm; 1.15 mm - 1.85 mm; 1.2 mm - 1.8 mm; 1.25 mm - 1.75 mm; 1.3 mm - 1.7 mm; 1.35 mm - 1.65 mm; 1.4 mm - 1.6 mm; 1.45 mm - 1.55 mm). Other embodiments of the disclosure provide a composite portion (B), where the shaft (B2) has a diameter 210 of 0.3 mm or greater (e.g., 0.32; 0.34; 0.36; 0.38; 0.4; 0.42; 0.44; 0.46; 0.48; 0.5; 0.52; 0.54; 0.56; 0.58; 0.6; 0.62; 0.64; 0.66; 0.68; 0.7; 0.72; 0.74; 0.76; 0.78; 0.8; 0.82; 0.84; 0.86; 0.88; 0.9; 0.92; 0.94; 0.96; 0.98; 1; 1.02; 1.04; 1.06); 1 mm or less (e.g., 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87; 0.85; 0.83; 0.81; 0.79; 0.77; 0.75; 0.73; 0.71; 0.69; 0.67; 0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51; 0.49; 0.47; 0.45; 0.43; 0.41; 0.39; 0.37; 0.35; 0.33; 0.31; 0.29; 0.27; 0.25); or 0.3 mm - 1 mm (e.g., 0.31 - 0.99 mm; 0.32 mm - 0.98 mm; 0.33 mm - 0.97 mm; 0.34 - 0.96 mm; 0.35 mm - 0.95 mm; 0.36 mm - 0.94 mm; 0.37 - 0.93 mm; 0.38 mm - 0.92 mm; 0.39 mm - 0.91 mm; 0.4 - 0.9 mm; 0.41 mm - 0.89 mm; 0.42 mm - 0.88 mm; 0.43 mm - 0.87 mm; 0.44 - 0.86 mm; 0.45 mm - 0.85 mm; 0.46 mm - 0.84 mm; 0.47 - 0.83 mm; 0.48 mm - 0.82 mm; 0.49 mm - 0.81 mm; 0.5 - 0.8 mm; 0.51 mm - 0.79 mm; 0.52 mm - 0.78 mm; 0.53 mm - 0.77 mm; 0.54 - 0.76 mm; 0.55 mm - 0.75 mm; 0.56 mm - 0.74 mm; 0.57- 0.73 mm; 0.58 mm - 0.72 mm; 0.59 mm - 0.71 mm; 0.6 - 0.7 mm; 0.61 mm - 0.69 mm; 0.62 mm -0.68 mm; 0.63 mm - 0.67 mm; 0.64 - 0.66 mm). The base (B3) of the composite portion (B) of a punctal plug or hybrid punctal plug of the disclosure provides a diameter 215 of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35;0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71;0.73; 0.75; 0.77; 0.79; 0.81; 0.83; 0.85; 0.87; 0.89; 0.91; 0.93; 0.95; 0.97; 0.99; 1.01; 1.03; 1.05; 1.07;1.09; 1.11; 1.13; 1.15; 1.17; 1.19; 1.21; 1.23; 1.25; 1.27; 1.29; 1.31); 1 mm or less (e.g., 0.98; 0.96;0.94; 0.92; 0.9; 0.88; 0.86; 0.84; 0.82; 0.8; 0.78; 0.76; 0.74; 0.72; 0.7; 0.68; 0.66; 0.64; 0.62; 0.6; 0.58;0.56; 0.54; 0.52; 0.5; 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 1 mm (e.g., 0.02 mm - 0.99 mm; 0.03 mm - 0.98 mm; 0.04 mm - 0.97 mm; 0.05 mm - 0.96 mm; 0.06 mm - 0.95 mm; 0.07 mm - 0.94 mm; 0.08 mm - 0.93 mm; 0.09 mm - 0.92 mm; 0.1 mm - 0.91 mm; 0.11 mm - 0.9 mm; 0.12 mm - 0.89 mm; 0.13 mm - 0.88 mm; 0.14 mm - 0.87 mm; 0.15 mm - 0.86 mm; 0.16 mm - 0.85 mm; 0.17 mm - 0.84 mm; 0.18 mm - 0.83 mm; 0.19 mm - 0.82 mm; 0.2 mm - 0.81 mm; 0.21 mm - 0.8 mm; 0.22 mm- 0.79 mm; 0.23 mm - 0.78 mm; 0.24 mm - 0.77 mm; 0.25 mm - 0.76 mm; 0.26 mm - 0.75 mm; 0.27 mm - 0.74 mm; 0.28 mm - 0.73 mm; 0.29 mm - 0.72 mm; 0.3 mm - 0.71 mm; 0.31 mm - 0.7 mm; 0.32 mm - 0.69 mm; 0.33 mm - 0.68 mm; 0.34 mm - 0.67 mm; 0.35 mm - 0.66 mm; 0.36 mm - 0.65 mm; 0.37 mm - 0.64 mm; 0.38 mm - 0.63 mm; 0.39 mm - 0.62 mm; 0.4 mm - 0.61 mm; 0.41 mm - 0.6 mm; 0.42 mm - 0.59 mm; 0.43 mm - 0.58 mm; 0.44 mm - 0.57 mm; 0.45 mm - 0.56 mm; 0.46 mm - 0.55 mm; 0.47 mm - 0.54 mm; 0.48 mm - 0.53 mm; 0.49 mm - 0.52 mm; 0.5 mm - 0.51 mm). In some embodiments, the diameter 205 of the head (Bl) is greater than the diameter 215 of the base (B3), which has a diameter that is greater than the diameter 210 of the shaft (B2).

[0030] Some embodiments are directed to a composite portion (B), where the shaft (B2) typically has a height 225 greater than the height 220 of the head (Bl) or the height 230 of the base (B3). For example, the height 220 of the head (Bl) comprises 0.1 mm or greater (e.g., 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39); 0.3 mm or less (e.g., 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04); or 0.1 mm - 0.3 mm (e.g., 0.11 mm - 0.29 mm; 0.12 mm - 0.28 mm; 0.13 mm - 0.27 mm; 0.14 mm - 0.26 mm; 0.15 mm - 0.25 mm; 0.16 mm - 0.24 mm; 0.17 mm - 0.23 mm; 0.18 mm - 0.22 mm; 0.19 mm - 0.21 mm). Other aspects provide a height 225 of the base (B3) comprising 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79); 0.5 mm or less (e.g., 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 0.5 mm (e.g., 0.02 mm - 0.49 mm; 0.03 mm - 0.48 mm; 0.04 mm- 0.47 mm; 0.05 mm - 0.46 mm; 0.06 mm - 0.45 mm; 0.07 mm - 0.44 mm; 0.08 mm - 0.43 mm; 0.09 mm - 0.42 mm; 0.1 mm - 0.41 mm; 0.11 mm - 0.4 mm; 0.12 mm - 0.39 mm; 0.13 mm - 0.38 mm; 0.14 mm - 0.37 mm; 0.15 mm - 0.36 mm; 0.16 mm - 0.35 mm; 0.17 mm - 0.34 mm; 0.18 mm - 0.33 mm; 0.19 mm - 0.32 mm; 0.2 mm - 0.31 mm; 0.21 mm - 0.3 mm; 0.22 mm - 0.29 mm; 0.23 mm - 0.28 mm; 0.24 mm - 0.27 mm; 0.25 mm - 0.26 mm). The length or height 225 of the shaft (B2) is designed to fit safely and comfortably in a punctum of a subject, and is only limited anatomically. The height 225 of the shaft (B2) from a center point at the bottom of the head (Bl) or the top of the shaft (B2), along a vertical axis through the center of the shaft (B2) to the bottom of the shaft (B2) or top of the base (B3) comprises 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5; 2.6; 2.7; 2.8; 2.9; 3; 3.1; 3.2; 3.3; 3.4; 3.5); 3 mm or less (e.g., 2.95;2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 0.95 mm - 2.55 mm; 1 mm - 2.5 mm; 1.05 mm - 2.45 mm; 1.1 mm - 2.4 mm; 1.15 mm - 2.35 mm; 1.2 mm - 2.3 mm; 1.25 mm - 2.25 mm; 1.3 mm - 2.2 mm; 1.35 mm - 2.15 mm; 1.4 mm - 2.1 mm; 1.45 mm - 2.05 mm; 1.5 mm - 2 mm; 1.55 mm - 1.95 mm; 1.6 mm - 1.9 mm; 1.65 mm - 1.85 mm; 1.7 mm - 1.8 mm). While, in some embodiments, the height 230 of the base (B3) comprises a height of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79); 0.5 mm or less (e.g., 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 0.5 mm (e.g., 0.02 mm - 0.49 mm; 0.03 mm - 0.48 mm; 0.04 mm - 0.47 mm; 0.05 mm - 0.46 mm; 0.06 mm - 0.45 mm; 0.07 mm - 0.44 mm; 0.08 mm - 0.43 mm; 0.09 mm - 0.42 mm; 0.1 mm - 0.41 mm; 0.11 mm - 0.4 mm; 0.12 mm - 0.39 mm; 0.13 mm - 0.38 mm; 0.14 mm - 0.37 mm; 0.15 mm - 0.36 mm; 0.16 mm - 0.35 mm; 0.17 mm - 0.34 mm; 0.18 mm - 0.33 mm; 0.19 mm - 0.32 mm; 0.2 mm - 0.31 mm; 0.21 mm - 0.3 mm; 0.22 mm - 0.29 mm; 0.23 mm - 0.28 mm; 0.24 mm - 0.27 mm; 0.25 mm - 0.26 mm). Other aspects are directed to the combined heights of the shaft (B2) and the base (B3) of the composite portion of a punctal plug of the disclosure comprises a total height 235 of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm).

[0031] FIG. 2C also shows the radii of rounded surfaces of the composite portion (B) that indicate the curvatures, 250, which is the radius, for example, 0.09 mm - 0.11 mm, of the edge of the base (B3); 260, which is the radius, for example, 0.04 mm - 0.06 mm, of the edge of the head (Bl); and 270, which is the radius, for example, 0. 19 mm - 0.21 mm, of the head (Bl).

[0032] FIGs. 3A-3C show an exemplary punctal plug or hybrid punctal plug 300 with a composite portion (B) having a tilted head (Bl) connectively attached to a shaft (B2), which is connectively attached to a base (B3), where the composite portion (B) is inserted and / or connectively attached to a polymer portion (A) or dome (Al) through a cavity (A2) via a cylindrical tunnel (A3) and base opening (A4). A portion of the shaft (B2) and the base (B3) are inserted and / or connectively attached to thepolymer portion (A) or dome (Al), where the base (B3) fits in the base opening (A4), while a portion of the shaft (B2) fits in the cylindrical tunnel (A3). In some aspects, the soft, flexible material of the polymer portion (A) or dome (Al) enables the cylindrical tunnel (A3) and the base opening (A4), both of which have dimensions, including diameters, smaller than the dimensions, including diameters, of the shaft (B2) and the base (B3), respectively, to sufficiently expand to accommodate the shaft and base that are inserted therein, where inserting the composite portion into the polymer portion forms the punctal plug or hybrid punctal plug of the disclosure with or without the use of a biocompatible glue, such as but not limited to fibrin glue, epoxy resin or adhesive, medical grade cyanoacrylate, medical grade silicone adhesive, or combinations thereof, in an amount sufficient to secure the composite portion (B) into the polymer portion (A). FIG. 3A illustrates an exemplary punctal plug 300, where a base (B3) is in the base opening (A4), while a portion of the shaft (B2) is in the cylindrical tunnel (A3) showing a portion of the composite portion (B) inserted in and / or connectively attached to the polymer portion (A). The diameter 305 of the polymer portion (A) or dome (Al) at the widest point is shown in FIG. 3A as being less than the height 330 from the bottom of the head (B 1) to the bottom of the dome (Al) via the central axis (A -axis) going through the center of the punctal plug (FIGs. 3A-3B). The total height 330 from the bottom of the head (Bl) to the bottom of the dome (Al) comprises 1 mm or greater (e.g., 1.02; 1.04; 1.06; 1.08; 1.1; 1.12; 1.14; 1.16; 1.18; 1.2; 1.22; 1.24; 1.26; 1.28; 1.3; 1.32; 1.34; 1.36; 1.38; 1.4; 1.42; 1.44; 1.46; 1.48; 1.5; 1.52; 1.54; 1.56; 1.58; 1.6; 1.62; 1.64; 1.66; 1.68; 1.7; 1.72; 1.74; 1.76; 1.78; 1.8; 1.82; 1.84; 1.86; 1.88; 1.9; 1.92; 1.94; 1.96; 1.98; 2; 2.02; 2.04; 2.06; 2.08; 2.1; 2.12; 2.14; 2.16; 2.18; 2.2; 2.22; 2.24; 2.26; 2.28; 2.3; 2.32; 2.34; 2.36; 2.38; 2.4; 2.42; 2.44; 2.46; 2.48; 2.5; 2.52; 2.54; 2.56; 2.58; 2.6; 2.62; 2.64; 2.66; 2.68; 2.7; 2.72; 2.74; 2.76; 2.78; 2.8; 2.82; 2.84; 2.86; 8.88; 2.9; 2.92; 2.94; 2.96; 2.98; 3; 3.02; 3.04; 3.06; 3.08; 3.1; 3.12; 3.14; 3.16; 3.18; 3.2; 3.22; 3.24; 3.26; 3.28; 3.3; 3.32; 3.34; 3.36; 3.38; 3.4; 3.42; 3.44; 3.46; 3.48; 3.5); 3 mm or less (e.g., 2.99; 2.97; 2.95; 2.93; 2.91; 2.89; 2.87; 2.85; 2.83; 2.81; 2.79; 2.77; 2.75; 2.73; 2.71; 2.69; 2.67; 2.65; 2.63; 2.61; 2.59;2.57; 2.55; 2.53; 2.51; 2.49; 2.47; 2.45; 2.43; 2.41; 2.39; 2.37; 2.35; 2.33; 2.31; 2.29; 2.27; 2.25; 2.23;2.21; 2.19; 2.17; 2.15; 2.13; 2.11; 2.09; 2.07; 2.05; 2.03; 2.01; 1.99; 1.97; 1.95; 1.93; 1.91; 1.89; 1.87;1.85; 1.83; 1.81; 1.79; 1.77; 1.75; 1.73; 1.71; 1.69; 1.67; 1.65; 1.63; 1.61; 1.59; 1.57; 1.55; 1.53; 1.51;1.49; 1.47; 1.45; 1.43; 1.41; 1.39; 1.37; 1.35; 1.33; 1.31; 1.29; 1.27; 1.25; 1.23; 1.21; 1.19; 1.17; 1.15;1.13; 1.11; 1.09; 1.07; 1.05; 1.03; 1.01; 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87; 0.85; 0.83; 0.81; 0.79;0.77; 0.75; 0.73; 0.71; 0.69; 0.67; 0.0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51); or 1 mm - 3 mm (e.g., 1.01 mm - 2.99 mm; 1.02 mm - 2.98 mm; 1.03 mm - 2.97 mm; 1.04 mm - 2.96 mm; 1.05 mm - 2.95 mm; 1.06 mm - 2.94 mm; 1.07 mm - 2.93 mm; 1.08 mm - 2.92 mm; 1.09 mm - 2.91 mm; 1.1 mm - 2.9 mm; 1.11 mm - 2.89 mm; 1.12 mm - 2.88 mm; 1.13 mm - 2.87 mm; 1.14 mm - 2.86 mm; 1.15 mm - 2.85 mm; 1.16 mm - 2.84 mm; 1.17 mm - 2.83 mm; 1.18 mm - 2.82 mm; 1.19 mm - 2.81 mm; 1.2 mm - 2.8 mm; 1.21 mm - 2.79 mm; 1.22 mm - 2.78 mm; 1.23 mm - 2.77 mm; 1.24 mm - 2.76 mm; 1.25 mm - 2.75 mm; 1.26 mm - 2.74 mm; 1.27 mm - 2.73 mm; 1.28 mm - 2.72 mm; 1.29 mm - 2.71 mm; 1.3 mm - 2.7 mm; 1.31 mm - 2.69 mm; 1.32 mm - 2.68 mm; 1.33 mm - 2.67 mm;1.34 mm - 2.66 mm; 1.35 mm - 2.65 mm; 1.36 mm - 2.64 mm; 1.37 mm - 2.63 mm; 1.38 mm - 2.62 mm; 1.39 mm - 2.61 mm; 1.4 mm - 2.6 mm; 1.41 mm - 2.59 mm; 1.42 mm - 2.58 mm; 1.43 mm - 2.57 mm; 1.44 mm - 2.56 mm; 1.45 mm - 2.55 mm; 1.46 mm - 2.54 mm; 1.47 mm - 2.53 mm; 1.48 mm - 2.52 mm; 1.49 mm - 2.51 mm; 1.5 mm - 2.5 mm; 1.51 mm - 2.49 mm; 1.52 mm - 2.48 mm; 1.53 mm - 2.47 mm; 1.54 mm - 2.46 mm; 1.55 mm - 2.45 mm; 1.56 mm - 2.44 mm; 1.57 mm - 2.43 mm; 1.58 mm - 2.42 mm; 1.59 mm - 2.41 mm; 1.6 mm - 2.4 mm; 1.61 mm - 2.39 mm; 1.62 mm - 2.38 mm; 1.63 mm - 2.37 mm; 1.64 mm - 2.36 mm; 1.65 mm - 2.35 mm; 1.66 mm - 2.34 mm; 1.67 mm - 2.33 mm; 1.68 mm - 2.32 mm; 1.69 mm - 2.31 mm; 1.7 mm - 2.3 mm; 1.71 mm - 2.29 mm; 1.72 mm - 2.28 mm; 1.73 mm - 2.27 mm; 1.74 mm - 2.26 mm; 1.75 mm - 2.25 mm; 1.76 mm - 2.24 mm; 1.77 mm - 2.23 mm; 1.78 mm - 2.22 mm; 1.79 mm - 2.21 mm; 1.8 mm - 2.2 mm; 1.81 mm - 2.19 mm; 1.82 mm - 2.18 mm; 1.83 mm - 2.17 mm; 1.84 mm - 2.16 mm; 1.85 mm - 2.15 mm; 1.86 mm - 2.14 mm; 1.87 mm - 2.13 mm; 1.88 mm - 2.12 mm; 1.89 mm - 2.11 mm; 1.9 mm - 2.1 mm; 1.91 mm - 2.09 mm; 1.92 mm - 2.08 mm; 1.93 mm - 2.07 mm; 1.94 mm - 2.06 mm; 1.95 mm - 2.05 mm; 1.96 mm - 2.04 mm; 1.97 mm - 2.03 mm; 1.98 mm - 2.02 mm; 1.99 mm - 2.01 mm). FIG. 3C illustrates a cross sectional view of an exemplary embodiment of the punctal plug 300 containing a tilted head (Bl), where the polymer portion (A) or dome (Al) is depicted by 310 and 320 as the composite portion (B). FIG. 3C also shows the initial dimensions of the cylindrical tunnel (A3) and the base opening (A4), which are expanded to accommodate the dimensions of the shaft (B2) and the base (B3). FIG. 3D provides an illustrative example of a punctal plug 300 and its exterior components comprising the polymer portion (A) or dome (Al) and the head (Bl) and shaft (B2) of the composite portion (B).

[0033] FIGs. 4A-4E show various views of another exemplary punctal plug 400. FIG. 4A provides a top view of the exemplary plug 400, where the oval shaped head (Bl) has dimensions that are smaller than that of the dome (Al), where in some embodiments, the diameter of the dome (Al) is altered to be wider or narrower than the diameter of the head (Bl), at least in one direction, or alternatively, the diameter of the head (B 1) is altered to be wider or narrower than the diameter of the dome (Al). FIGs. 4B-4C illustrate side views of a cross section of the punctal plug 400 comprising a straight head (Bl) that is perpendicular to a shaft (B2). Also shown are the original dimensions of the cylindrical tunnel (A3) and the base opening (A4), where a portion of the shaft (B2) and the base (B3) are inserted, respectively. FIGs. 4D-4E show alternative views of the punctal plug 400, where FIG. 4E shows the underside of the dome (Al), which is a flat bottom dome, and underneath the head (Bl).

[0034] A top view of another exemplary punctal plug 500 embodied here is illustrated in FIG. 5A, where the oval shaped head (Bl) has dimensions that extend over or are larger than that of the dome (Al). FIGs. 5B-5C illustrate side views of a cross section of the punctal plug 500 comprising a straight head (Bl) that is perpendicular to a shaft (B2), where the oval shaped head (Bl) is at its wide diameter (FIG. 5B) and narrow diameter (FIG. 5C). Also shown are the original dimensions of the cylindricaltunnel (A3) and the base opening (A4), where a portion of the shaft (B2) and the base (B3) are inserted, respectively. FIGs. 5D-5E show alternative views of the punctal plug 500, where FIG. 5E shows the underside of the dome (Al), which is a flat bottom dome, and underneath the head (Bl).

[0035] FIGs. 6A-6D show various views of an exemplary punctal plug 600 having a composite portion (B) comprising an ovoid shaped head (Bl) connectively attached to a shaft (B2), which is connective ly attached to a polymer portion (A) or dome (Al).

[0036] FIGs. 7A-7D show multiple views of an exemplary embodiment of a punctal plug 700 having a composite portion (B) comprising a straight head (Bl) which is perpendicular to and connectively attached to the shaft (B2), which is connectively attached to a polymer portion (A) or a flat-bottom dome (Al).Methods of Use

[0037] In various embodiments described here, a method, comprising administering or inserting the punctal plugs of the disclosure (comprising (a) a polymer portion (A), where the polymer portion comprises a dome (Al), where the dome (Al) comprises a cavity (A2), where the cavity comprises a cylindrical tunnel (A3) and a base opening at a distal end (A4), where the base opening has a diameter greater than a diameter of the cylindrical tunnel; and (b) a composite portion (B), where the composite portion comprises a head (Bl) connected to a shaft (B2) connected to a base at a distal end (B3), where the composite portion (b) is connected to the polymer portion (a), where the base (B3) and a portion of the shaft (B2) of the composite portion (b) are configured to insert into the cavity (A2) of the polymer portion (a), where the dimensions of the cavity (A2) is less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2)), into a punctum of a subject in need thereof, where the subject suffers from an ocular disease or condition, or symptoms thereof, and where use of the punctal plugs described here treats the ocular disease or condition, or symptoms thereof, in the subject. The method disclosed here can include a head (Bl) portion of a punctal plug, where the punctal plug is configured such that the majority or all of the active agent described here is released through the head (Bl) of the composite portion. The ocular disease or condition, or symptom useful in the various embodiments describe here is selected from the group consisting of: dry eye disease (Keratoconjunctivitis sicca (KCS)); Stevens-Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; increased or high intraocular pressure; punctal stenosis; ocular hypertension; and any combinations thereof.

[0038] Other embodiments are directed to a method, comprising: administering or inserting a punctal plug of the disclosure (comprising (a) a polymer portion (A), where the polymer portion comprises a dome (Al), where the dome (Al) comprises a cavity (A2), where the cavity comprises a cylindrical tunnel (A3) and a base opening at a distal end (A4), where the base opening has a diameter greater than a diameter of the cylindrical tunnel; and (b) a composite portion (B), where the composite portioncomprises a head (Bl) connected to a shaft (B2) connected to a base at a distal end (B3), where the composite portion (b) is connected to the polymer portion (a), where the base (B3) and a portion of the shaft (B2) of the composite portion (b) are configured to insert into the cavity (A2) of the polymer portion (a), where the dimensions of the cavity (A2) is less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2), where the composite portion comprises: a binder; an absorbent material; and optionally, an active agent or combinations of active agents), into a punctum of a subject in need thereof, where the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, where the punctal plug the polymer portion (A) comprises an impermeable material (or an essentially impermeable material); releasing the active agent from an exposed portion (z.e., not inside or covered by the polymer portion; exposed shaft (B2) and / or head (Bl)) of the composite portion (B) towards the punctal opening of the subject, thereby treating the subject in need thereof suffering from the ocular disease or condition (e.g., dry eye disease; Stevens- Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; punctal stenosis; ocular hypertension; and any combinations thereof). Some aspects provide for a method where releasing the active agent can occur primarily or essentially from the head (Bl) of the composite portion (B) of the punctal plug of the disclosure, providing an effective amount of active agent to treat the ocular disease or condition. The active agent useful in the punctal plugs of the disclosure can be any active agent known to treat an ocular disease or condition, or symptoms thereof. Without being bound by theory, the active agent is essentially released from the unexposed composite portion (B), z.e., the composite portion that is not surrounded by the polymer portion (A) or dome (Al), where the majority of active agent is released from the head (Bl) of the composite portion (B), where some active agent can also be released from the shaft (B2). In some aspects of the disclosure, the punctal plugs described here provide an efficient active agent delivery system, such that the majority of active agent is delivered to the surface of the eye and less if any to the surrounding tissues z.e., active agent essentially does not get released in the canaliculus, lacrimal sac, or tear duct, with the majority of active agent released through the head (Bl) to the surface of the eye. Non-limiting active agents for use in the punctal plug or hybrid punctal plug of the disclosure for treating ophthalmological diseases or conditions include: prostaglandin analogs (e.g., bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod); antibiotics (e.g., fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline); macrolides (e.g., 12-membered (e.g., methymycin); 14-membered (e.g., clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin); 15-membered (e.g., azithromycin); 16-membered (e.g., miokamycin, rokitamycin, tilmicosin); ketolides (e.g., telithromycin, cethromycin, solithromycin)); immunosupressants (e.g., tacrolimus, pimecrolimus, sirolimus, cyclosporine, cyclosporine corticosteroids (e.g., dexamethasone; ceftazidime)); beta-blockers (e.g., timolol, levobunolol, metipranolol, carteolol); antifungals (e.g. polyenes, azoles, allylamines, echinocandins); antihistamines (e.g., cetirizine, desloratadine, diphenhydramine, epinastine, fexofenadine, ketotifen, levocetirizine,olopatadine); anti-inflammatory agents (e.g., ketorolac, loteprednol); tear lubricants (e.g., hydroxypropyl cellulose); and tear producers (e.g., cholinergics (e.g., pilocarpine, cevimeline)); or any combinations thereof. In some aspects of the disclosure, the composite portion (B) comprises an active agent selected from the group consisting of: bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod; fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline; methymycin; clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin; azithromycin; miokamycin, rokitamycin, tilmicosin; telithromycin, cethromycin, solithromycin; tacrolimus, pimecrolimus, sirolimus, cyclosporine; dexamethasone; ceftazidime; hydroxypropyl cellulose; pilocarpine, cevimeline; tacrolimus; and any combinations thereof.

[0039] Use of a punctal plug or hybrid punctal plug of various embodiments of the disclosure, for the treatment of ocular diseases or conditions, or symptoms thereof, in a subject in need thereof. In some embodiments, the ocular disease or condition, or symptom thereof is selected from the group consisting of: dry eye disease (Keratoconjunctivitis sicca (KCS)); Stevens-Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; increased or high intraocular pressure; punctal stenosis; ocular hypertension; and any combinations thereof.DEFINITIONS

[0040] All terms used herein are intended to have their ordinary meaning in the art unless otherwise provided. All concentrations are in terms of percentage by weight of the specified component relative to the entire weight of the topical composition, unless otherwise defined.

[0041] As used herein, “a” or “an” shall mean one or more. As used herein when used in conjunction with the word “comprising,” the words “a” or “an” mean one or more than one. As used herein “another” means at least a second or more.

[0042] As used herein, all ranges of numeric values include the endpoints and all possible values disclosed between the disclosed values. The exact values of all half integral numeric values are also contemplated as specifically disclosed and as limits for all subsets of the disclosed range. For example, a range of from 0.1% to 3% specifically discloses a percentage of 0.1%, 1%, 1.5%, 2.0%, 2.5%, and 3%. Additionally, a range of 0.1 to 3% includes subsets of the original range including from 0.5% to 2.5%, from 1% to 3%, from 0.1% to 2.5%, etc. It will be understood that the sum of all weight % of individual components will not exceed 100%.

[0043] By "consist essentially" it is meant that the ingredients include only the listed components along with the normal impurities present in commercial materials and with any other additives present at levels which do not affect the operation of the disclosure, for instance at levels less than 5% by weight or less than 1% or even 0.5% by weight.

[0044] The term “effective amount” or “therapeutically effective amount” of an active agent (e.g for treating an ocular disease or condition described here), as used herein, is that amount sufficient to effect beneficial or desired results, such as clinical results, and, as such, an “effective amount” depends upon the context in which it is being applied. In some embodiments, the active agents are administered in an effective amount for the treatment or prophylaxis of a disease disorder or condition, such as an ocular disease or condition. In another embodiment, in the context of administering to a subject in need thereof, an active agent that is an anti -ocular disease or condition, an effective amount of an active agent is, for example, an amount sufficient to achieve alleviation or amelioration or prevention or prophylaxis of one or more symptoms or conditions; diminishment of extent of disease, disorder, or condition; stabilized (i.e., not worsening) state of disease, disorder, or condition; preventing the disease, disorder, or condition; delaying or slowing the progress of the disease, disorder, or condition; amelioration or palliation of the disease, disorder, or condition (e.g., ocular disease or condition: dry eye disease; Stevens-Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; punctal stenosis; ocular hypertension; and any combinations thereof); and remission (whether partial or total), whether detectable or undetectable, as compared to the response obtained without administration of the active agent.

[0045] Determining an effective amount of an active agent to be delivered can depend upon a number of factors including, for example, the active agent and biological activity of the substance, the age and weight of the subject, the precise condition requiring treatment and its severity, and the route of administration. The frequency of treatments depends upon a number of factors, such as the amount of the therapeutic active agent released from the punctal plug of the disclosure, as well as the health and history of the subject. The sizing of the punctal plug of the disclosure, precise amount of active, and length of insertion time will depend on the severity of the ocular disease or condition, or symptoms thereof, in a subject in need thereof, and be determined by the attending physician or practitioner. The punctal plugs of the present disclosure can be administered to any “subject”. Typical “subjects” include any animal, such as mammals. Non -limiting examples of mammals include humans, dogs, cats, cattle, horses, and the like, where the mammal is in need of treatment of an ocular disease or condition.SPECIFIC EMBODIMENTS

[0046] Non-limiting specific embodiments are described below each of which is considered to be within the scope of the present disclosure.

[0047] Embodiment 1. A punctal plug, comprising:(a) a polymer portion (A), wherein the polymer portion comprises a dome (Al), wherein the dome (Al) comprises a cavity (A2),wherein the cavity comprises a cylindrical tunnel (A3) and a base opening at a distal end (A4), wherein the base opening has a diameter greater than a diameter of the cylindrical tunnel; and(b) a composite portion (B), wherein the composite portion comprises a head (B 1) connected to a shaft (B2) connected to a base at a distal end (B3), wherein the composite portion (b) is connected to the polymer portion (a), wherein the base (B3) and a portion of the shaft (B2) of the composite portion (b) are configured to insert into the cavity (A2) of the polymer portion (a), wherein the dimensions of the cavity (A2) are less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2).

[0048] Embodiment 2. The punctal plug of embodiment 1, wherein the polymer portion (A) comprises a flexible, chemically inert polymer.

[0049] Embodiment 3. The punctal plug of embodiment 2, wherein the polymer is selected from the group consisting of: silicone, silicone -based polymer, polyacrylate, polyurethane, and combinations / blends thereof (e.g., liquid silicone rubber, such as NUSIL MED-4840 / -4850 / -4860 / - 4870 / -4880; polyurethane rubber such as POLYTEK PT Flex 50 / 60 / 70 / 85; polyacrylate acrylic rubber such as Robinson Rubber Products ; where the material has a hardness range of Shore A 40-90.

[0050] Embodiment 4. The punctal plug of any one of embodiments 1-3, wherein the polymer portion (A) comprises an impermeable material (or an essentially impermeable material).

[0051] Embodiment 5. The punctal plug of any one of embodiments 1-4, wherein the dome (Al) comprises a flat-bottom or a rounded dome shape, wherein the flat bottom comprises a length of 0.1 mm or greater (e.g., 0.3; 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.1 mm - 2 mm (e.g., 0.2 mm - 1.9 mm; 0.3 mm - 1.8 mm; 0.4 mm - 1.7 mm; 0.5 mm - 1.6 mm; 0.6 mm - 1.5 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm).

[0052] Embodiment 6. The punctal plug of any one of embodiments 1-5, wherein the polymer portion (A) comprises a diameter (e.g., at its widest point) of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65;1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm- 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm- 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm).

[0053] Embodiment 7. The punctal plug of any one of embodiments 1-6, wherein the polymer portion (A) comprises a height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm- 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm).

[0054] Embodiment 8. The punctal plug of any one of embodiments 1-7, wherein the cylindrical tunnel (A3) comprises a diameter of 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.1 mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm - 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm).

[0055] Embodiment 9. The punctal plug of any one of embodiments 1-8, wherein the cylindrical tunnel (A3) comprises a height of 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.1 mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm - 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm).

[0056] Embodiment 10. The punctal plug of any one of embodiments 1-9, wherein the base opening (A4) comprises a diameter of 0.3 mm or greater (e.g., 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9; 2.1; 2.3; 2.5); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.3 mm - 2 mm (e.g., 0.4 mm - 1.9 mm; 0.5 mm - 1.8 mm; 0.6 mm - 1.7 mm; 0.7 mm - 1.6 mm; 0.8 mm - 1.5 mm; 0.9 mm - 1.4 mm; 1 mm - 1.3 mm; 1.1 mm - 1.2 mm).

[0057] Embodiment 11. The punctal plug of any one of embodiments 1-10, wherein the base opening (A4) comprises a height of 0.05 mm or greater (e.g., 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5); 2 mm or less (e.g., 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.05 mm - 2 mm (e.g., 0.1 mm - 1.95 mm; 0.15 mm - 1.9 mm; 0.2 mm - 1.85 mm; 0.25 mm - 1.8 mm; 0.3 mm - 1.75 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm).

[0058] Embodiment 12. The punctal plug of any one of embodiments 1-11, wherein the head (Bl) of the composite portion (B) is essentially perpendicular to the shaft (B2).

[0059] Embodiment 13. The punctal plug of any one of embodiments 1-11, wherein the head (Bl) of the composite portion (B) is positioned at an angle as compared to the shaft (B2).

[0060] Embodiment 14. The punctal plug of embodiment 13, wherein the angle comprises 90° or greater (e.g., 91; 92; 93; 94; 95; 96; 97; 98; 99; 100; 101; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125); 120.5° or less (e.g., 119.5; 118.5; 117.5; 116.5; 115.5; 114.5; 113.5; 112.5; 111.5; 110.5; 109.5; 108.5; 107.5; 106.5; 105.5; 104.5; 103.5; 102.5; 101.5; 100.5; 99.5; 98.5; 97.5; 96.5; 95.5; 94.5; 93.5; 92.5; 91.5; 90.5; 89.5; 88.5; 87.5; 86.5; 85.5); or 90° - 120.5° (e.g., 90.5° - 120°; 91° - 119.5°; 91.5° - 119°; 92° - 118.5°; 92.5° - 118°; 93° - 117.5°; 93.5° - 117°; 94° - 116.5°; 94.5° - 116°; 95° - 115.5°; 95.5° - 115°; 96° - 114.5°; 96.5° - 114°; 97° - 113.5°; 97.5° - 113°; 98° - 112.5°; 98.5° - 112°; 99° - 111.5°; 99.5° - 111°; 100° - 110.5°; 101.5° - 110°; 102° - 109.5°; 102.5° - 109°; 103° - 108.5°; 103.5° - 108°; 104° - 107.5°; 104.5° - 107°; 105° - 106.5°; 105.5° - 106°).

[0061] Embodiment 15. The punctal plug of any one of embodiments 1-14, wherein the composite portion comprises: a binder; an absorbent material; and optionally, an active agent or combinations thereof.

[0062] Embodiment 16. The punctal plug of embodiment 15, wherein the binder comprises epoxy.

[0063] Embodiment 17. The punctal plug of any one of embodiments 15-16, wherein the absorbent material comprises fumed silica, hydroxypropyl methylcellulose (HPMC)-based polymer, or any combinations or blends thereof.

[0064] Embodiment 18. The punctal plug of any one of embodiments 15-17, wherein the active agent comprises an active agent for treating an ocular disease or condition or combinations thereof.

[0065] Embodiment 19. The punctal plug of embodiment 18, wherein the active agent is selected from the group consisting of: prostaglandin analogs (e.g., bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod); antibiotics (e.g., fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline); macrolides (e.g., 12-membered (e.g., methymycin); 14-membered (e.g., clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin); 15-membered (e.g., azithromycin); 16-membered (e.g., miokamycin, rokitamycin, tilmicosin); ketolides (e.g., telithromycin, cethromycin, solithromycin)); immunosupressants (e.g., tacrolimus, pimecrolimus, sirolimus, cyclosporine), corticosteroids (e.g., dexamethasone; ceftazidime)); beta-blockers (e.g., timolol, levobunolol, metipranolol, carteolol); antifungals (e.g. polyenes, azoles, allylamines, echinocandins); antihistamines (e.g., cetirizine, desloratadine, diphenhydramine, epinastine, fexofenadine, ketotifen, levocetirizine, olopatadine); antiinflammatory agents (e.g., ketorolac, loteprednol); tear lubricants (e.g., hydroxypropyl cellulose); and tear producers (e.g., cholinergics (e.g., pilocarpine, cevimeline)); or any combinations thereof.

[0066] Embodiment 20. The punctal plug of embodiment 18, wherein the active agent is selected from the group consisting of: bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod; fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline; methymycin; clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin; azithromycin; miokamycin, rokitamycin, tilmicosin; telithromycin, cethromycin, solithromycin; tacrolimus, pimecrolimus, sirolimus, cyclosporine; dexamethasone; ceftazidime; hydroxypropyl cellulose; pilocarpine, cevimeline; tacrolimus; and any combinations thereof.

[0067] Embodiment 21. The punctal plug of any one of embodiments 1-20, wherein the head(Bl) comprises a diameter of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4); 2.5 or less (e.g., 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15); or 0.5 mm - 2.5 mm (e.g., 0.55 mm - 2.45 mm; 0.6 mm - 2.4 mm; 0.65 mm - 2.35 mm; 0.7 mm - 2.3 mm; 0.75 mm - 2.25 mm; 0.8 mm - 2.2 mm; 0.85 mm - 2.15 mm; 0.9 mm - 2.1 mm; 0.95 mm - 2.05 mm; 1 mm - 2 mm; 1.05 mm - 1.95 mm; 1.1 mm - 1.9 mm; 1.15 mm - 1.85 mm; 1.2 mm - 1.8 mm; 1.25 mm - 1.75 mm; 1.3 mm - 1.7 mm; 1.35 mm - 1.65 mm; 1.4 mm - 1.6 mm; 1.45 mm - 1.55 mm).

[0068] Embodiment 22. The punctal plug of any one of embodiments 1-21, wherein the head (Bl) comprises a height of 0.1 mm or greater (e.g., 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39); 0.3 mm or less (e.g., 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04); or 0.1 mm - 0.3 mm (e.g., 0.11 mm - 0.29 mm; 0.12 mm - 0.28 mm; 0.13 mm - 0.27 mm; 0.14 mm - 0.26 mm; 0.15 mm - 0.25 mm; 0.16 mm - 0.24 mm; 0.17 mm - 0.23 mm; 0.18 mm - 0.22 mm; 0.19 mm - 0.21 mm).

[0069] Embodiment 23. The punctal plug of any one of embodiments 1-22, wherein the shaft (B2) comprises a diameter of 0.3 mm or greater (e.g., 0.32; 0.34; 0.36; 0.38; 0.4; 0.42; 0.44; 0.46; 0.48; 0.5; 0.52; 0.54; 0.56; 0.58; 0.6; 0.62; 0.64; 0.66; 0.68; 0.7; 0.72; 0.74; 0.76; 0.78; 0.8; 0.82; 0.84; 0.86; 0.88; 0.9; 0.92; 0.94; 0.96; 0.98; 1; 1.02; 1.04; 1.06); 1 mm or less (e.g., 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87; 0.85; 0.83; 0.81; 0.79; 0.77; 0.75; 0.73; 0.71; 0.69; 0.67; 0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51; 0.49; 0.47; 0.45; 0.43; 0.41; 0.39; 0.37; 0.35; 0.33; 0.31; 0.29; 0.27; 0.25); or 0.3 mm - 1 mm (e.g., 0.31 - 0.99 mm; 0.32 mm - 0.98 mm; 0.33 mm - 0.97 mm; 0.34 - 0.96 mm; 0.35 mm - 0.95 mm; 0.36 mm - 0.94 mm; 0.37 - 0.93 mm; 0.38 mm - 0.92 mm; 0.39 mm - 0.91 mm; 0.4 - 0.9 mm; 0.41 mm - 0.89 mm; 0.42 mm - 0.88 mm; 0.43 mm - 0.87 mm; 0.44 - 0.86 mm; 0.45 mm - 0.85 mm; 0.46 mm - 0.84 mm; 0.47 - 0.83 mm; 0.48 mm - 0.82 mm; 0.49 mm - 0.81 mm; 0.5 - 0.8 mm; 0.51 mm - 0.79 mm; 0.52 mm - 0.78 mm; 0.53 mm - 0.77 mm; 0.54 - 0.76 mm; 0.55 mm - 0.75 mm; 0.56 mm - 0.74 mm; 0.57 - 0.73 mm; 0.58 mm - 0.72 mm; 0.59 mm - 0.71 mm; 0.6 - 0.7 mm; 0.61 mm - 0.69 mm; 0.62 mm - 0.68 mm; 0.63 mm - 0.67 mm; 0.64 - 0.66 mm).

[0070] Embodiment 24. The punctal plug of any one of embodiments 1-23, wherein the shaft (B2) comprises a height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5; 2.6; 2.7; 2.8; 2.9; 3; 3.1; 3.2; 3.3; 3.4; 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 0.95 mm - 2.55 mm; 1 mm - 2.5 mm; 1.05 mm - 2.45 mm; 1.1 mm - 2.4 mm; 1.15 mm - 2.35 mm; 1.2 mm - 2.3 mm; 1.25 mm - 2.25 mm; 1.3 mm - 2.2 mm; 1.35 mm - 2.15 mm; 1.4 mm - 2.1 mm; 1.45 mm - 2.05 mm; 1.5 mm - 2 mm; 1.55 mm - 1.95 mm; 1.6 mm - 1.9 mm; 1.65 mm - 1.85 mm; 1.7 mm - 1.8 mm).

[0071] Embodiment 25. The punctal plug of any one of embodiments 1-24, wherein the base (B3) comprises a diameter of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17;0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53;0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79; 0.81; 0.83; 0.85; 0.87; 0.89;0.91; 0.93; 0.95; 0.97; 0.99; 1.01; 1.03; 1.05; 1.07; 1.09; 1.11; 1.13; 1.15; 1.17; 1.19; 1.21; 1.23; 1.25;1.27; 1.29; 1.31); 1 mm or less (e.g., 0.98; 0.96; 0.94; 0.92; 0.9; 0.88; 0.86; 0.84; 0.82; 0.8; 0.78; 0.76; 0.74; 0.72; 0.7; 0.68; 0.66; 0.64; 0.62; 0.6; 0.58; 0.56; 0.54; 0.52; 0.5; 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 1 mm (e.g., 0.02 mm - 0.99 mm; 0.03 mm - 0.98 mm; 0.04 mm - 0.97 mm; 0.05 mm - 0.96 mm; 0.06 mm - 0.95 mm; 0.07 mm - 0.94 mm; 0.08 mm - 0.93 mm; 0.09 mm - 0.92 mm; 0.1 mm - 0.91 mm; 0.11 mm - 0.9 mm; 0.12 mm - 0.89 mm; 0.13 mm - 0.88 mm; 0.14 mm - 0.87 mm; 0.15 mm - 0.86 mm; 0.16 mm - 0.85 mm; 0.17 mm - 0.84 mm; 0.18 mm - 0.83 mm; 0.19 mm - 0.82 mm; 0.2 mm - 0.81 mm; 0.21 mm - 0.8 mm; 0.22 mm - 0.79 mm; 0.23 mm - 0.78 mm; 0.24 mm - 0.77mm; 0.25 mm - 0.76 mm; 0.26 mm - 0.75 mm; 0.27 mm - 0.74 mm; 0.28 mm - 0.73 mm; 0.29 mm - 0.72 mm; 0.3 mm - 0.71 mm; 0.31 mm - 0.7 mm; 0.32 mm - 0.69 mm; 0.33 mm - 0.68 mm; 0.34 mm - 0.67 mm; 0.35 mm - 0.66 mm; 0.36 mm - 0.65 mm; 0.37 mm - 0.64 mm; 0.38 mm - 0.63 mm; 0.39 mm - 0.62 mm; 0.4 mm - 0.61 mm; 0.41 mm - 0.6 mm; 0.42 mm - 0.59 mm; 0.43 mm - 0.58 mm; 0.44 mm - 0.57 mm; 0.45 mm - 0.56 mm; 0.46 mm - 0.55 mm; 0.47 mm - 0.54 mm; 0.48 mm - 0.53 mm; 0.49 mm - 0.52 mm; 0.5 mm - 0.51 mm).

[0072] Embodiment 26. The punctal plug of any one of embodiments 1-25, wherein the base (B3) comprises a height of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79); 0.5 mm or less (e.g., 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 0.5 mm (e.g., 0.02 mm - 0.49 mm; 0.03 mm - 0.48 mm; 0.04 mm - 0.47 mm; 0.05 mm - 0.46 mm; 0.06 mm - 0.45 mm; 0.07 mm - 0.44 mm; 0.08 mm - 0.43 mm; 0.09 mm - 0.42 mm; 0.1 mm - 0.41 mm; 0.11 mm - 0.4 mm; 0.12 mm - 0.39 mm; 0.13 mm - 0.38 mm; 0.14 mm - 0.37 mm; 0.15 mm - 0.36 mm; 0.16 mm - 0.35 mm; 0.17 mm - 0.34 mm; 0.18 mm - 0.33 mm; 0.19 mm - 0.32 mm; 0.2 mm - 0.31 mm; 0.21 mm - 0.3 mm; 0.22 mm - 0.29 mm; 0.23 mm - 0.28 mm; 0.24 mm - 0.27 mm; 0.25 mm - 0.26 mm).

[0073] Embodiment 27. The punctal plug of any one of embodiments 1-26, wherein the shaft (B2) and the base (B3) comprise a total height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm).

[0074] Embodiment 28. The punctal plug of any one of embodiments 1 -27, wherein the bottom of the head (Bl) to the bottom of the dome (Al) comprises a total height of 1 mm or greater (e.g., 1.02; 1.04; 1.06; 1.08; 1.1; 1.12; 1.14; 1.16; 1.18; 1.2; 1.22; 1.24; 1.26; 1.28; 1.3; 1.32; 1.34; 1.36; 1.38; 1.4; 1.42; 1.44; 1.46; 1.48; 1.5; 1.52; 1.54; 1.56; 1.58; 1.6; 1.62; 1.64; 1.66; 1.68; 1.7; 1.72; 1.74; 1.76; 1.78; 1.8; 1.82; 1.84; 1.86; 1.88; 1.9; 1.92; 1.94; 1.96; 1.98; 2; 2.02; 2.04; 2.06; 2.08; 2.1; 2.12; 2.14; 2.16; 2.18; 2.2; 2.22; 2.24; 2.26; 2.28; 2.3; 2.32; 2.34; 2.36; 2.38; 2.4; 2.42; 2.44; 2.46; 2.48; 2.5; 2.52; 2.54; 2.56; 2.58; 2.6; 2.62; 2.64; 2.66; 2.68; 2.7; 2.72; 2.74; 2.76; 2.78; 2.8; 2.82; 2.84; 2.86; 8.88; 2.9; 2.92; 2.94; 2.96; 2.98; 3; 3.02; 3.04; 3.06; 3.08; 3.1; 3.12; 3.14; 3.16; 3.18; 3.2; 3.22; 3.24; 3.26; 3.28; 3.3; 3.32; 3.34; 3.36; 3.38; 3.4; 3.42; 3.44; 3.46; 3.48; 3.5); 3 mm or less (e.g., 2.99 2.97; 2.95; 2.93; 2.91;2.89; 2.87; 2.85; 2.83; 2.81; 2.79; 2.77; 2.75; 2.73; 2.71; 2.69; 2.67; 2.65; 2.63; 2.61; 2.59; 2.57; 2.55;2.53; 2.51; 2.49; 2.47; 2.45; 2.43; 2.41; 2.39; 2.37; 2.35; 2.33; 2.31; 2.29; 2.27; 2.25; 2.23; 2.21; 2.19;2.17; 2.15; 2.13; 2.11; 2.09; 2.07; 2.05; 2.03; 2.01; 1.99; 1.97; 1.95; 1.93; 1.91; 1.89; 1.87; 1.85; 1.83;1.81; 1.79; 1.77; 1.75; 1.73; 1.71; 1.69; 1.67; 1.65; 1.63; 1.61; 1.59; 1.57; 1.55; 1.53; 1.51; 1.49; 1.47;1.45; 1.43; 1.41; 1.39; 1.37; 1.35; 1.33; 1.31; 1.29; 1.27; 1.25; 1.23; 1.21; 1.19; 1.17; 1.15; 1.13; 1.11;1.09; 1.07; 1.05; 1.03; 1.01; 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87; 0.85; 0.83; 0.81; 0.79; 0.77; 0.75;0.73; 0.71; 0.69; 0.67; 0.0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51); or 1 mm - 3 mm (e.g., 1.01 mm- 2.99 mm; 1.02 mm - 2.98 mm; 1.03 mm - 2.97 mm; 1.04 mm - 2.96 mm; 1.05 mm - 2.95 mm; 1.06 mm - 2.94 mm; 1.07 mm - 2.93 mm; 1.08 mm - 2.92 mm; 1.09 mm - 2.91 mm; 1.1 mm - 2.9 mm; 1.11 mm - 2.89 mm; 1.12 mm - 2.88 mm; 1.13 mm - 2.87 mm; 1.14 mm - 2.86 mm; 1.15 mm - 2.85 mm; 1.16 mm - 2.84 mm; 1.17 mm - 2.83 mm; 1.18 mm - 2.82 mm; 1.19 mm - 2.81 mm; 1.2 mm - 2.8 mm; 1.21 mm - 2.79 mm; 1.22 mm - 2.78 mm; 1.23 mm - 2.77 mm; 1.24 mm - 2.76 mm; 1.25 mm - 2.75 mm; 1.26 mm - 2.74 mm; 1.27 mm - 2.73 mm; 1.28 mm - 2.72 mm; 1.29 mm - 2.71 mm; 1.3 mm - 2.7 mm; 1.31 mm - 2.69 mm; 1.32 mm - 2.68 mm; 1.33 mm - 2.67 mm; 1.34 mm - 2.66 mm; 1.35 mm - 2.65 mm; 1.36 mm - 2.64 mm; 1.37 mm - 2.63 mm; 1.38 mm - 2.62 mm; 1.39 mm - 2.61 mm; 1.4 mm - 2.6 mm; 1.41 mm - 2.59 mm; 1.42 mm - 2.58 mm; 1.43 mm - 2.57 mm; 1.44 mm- 2.56 mm; 1.45 mm - 2.55 mm; 1.46 mm - 2.54 mm; 1.47 mm - 2.53 mm; 1.48 mm - 2.52 mm; 1.49 mm - 2.51 mm; 1.5 mm - 2.5 mm; 1.51 mm - 2.49 mm; 1.52 mm - 2.48 mm; 1.53 mm - 2.47 mm; 1.54 mm - 2.46 mm; 1.55 mm - 2.45 mm; 1.56 mm - 2.44 mm; 1.57 mm - 2.43 mm; 1.58 mm - 2.42 mm; 1.59 mm - 2.41 mm; 1.6 mm - 2.4 mm; 1.61 mm - 2.39 mm; 1.62 mm - 2.38 mm; 1.63 mm - 2.37 mm; 1.64 mm - 2.36 mm; 1.65 mm - 2.35 mm; 1.66 mm - 2.34 mm; 1.67 mm - 2.33 mm; 1.68 mm - 2.32 mm; 1.69 mm - 2.31 mm; 1.7 mm - 2.3 mm; 1.71 mm - 2.29 mm; 1.72 mm - 2.28 mm; 1.73 mm - 2.27 mm; 1.74 mm - 2.26 mm; 1.75 mm - 2.25 mm; 1.76 mm - 2.24 mm; 1.77 mm - 2.23 mm; 1.78 mm - 2.22 mm; 1.79 mm - 2.21 mm; 1.8 mm - 2.2 mm; 1.81 mm - 2.19 mm; 1.82 mm - 2.18 mm; 1.83 mm - 2.17 mm; 1.84 mm - 2.16 mm; 1.85 mm - 2.15 mm; 1.86 mm - 2.14 mm; 1.87 mm - 2.13 mm; 1.88 mm - 2.12 mm; 1.89 mm - 2.11 mm; 1.9 mm - 2.1 mm; 1.91 mm - 2.09 mm; 1.92 mm - 2.08 mm; 1.93 mm - 2.07 mm; 1.94 mm - 2.06 mm; 1.95 mm - 2.05 mm; 1.96 mm - 2.04 mm; 1.97 mm - 2.03 mm; 1.98 mm - 2.02 mm; 1.99 mm - 2.01 mm).

[0075] Embodiment 29. The punctal plug of any one of embodiments 1-28, wherein the dimensions of the cylindrical tunnel (A3) and the base opening (A4) are less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2).

[0076] Embodiment 30. The punctal plug of any one of embodiments 1-29, wherein an outer surface of the punctal plug or portion thereof comprises a coating.

[0077] Embodiment 31. The punctal plug of embodiment 30, wherein the coating comprises butvar and / or parylene.

[0078] Embodiment 32. The punctal plug of any one of embodiments 1-31, wherein the insertion occurs to insert the composite portion into the polymer portion.

[0079] Embodiment 33. The punctal plug of any one of embodiments 1-32, wherein the insertion occurs to insert the composite portion into the polymer portion, wherein the composite portion and the polymer portion are secured together with a biocompatible glue.

[0080] Embodiment 34. The punctal plug of embodiment 33, wherein the biocompatible glue comprises fibrin glue, epoxy resin or adhesive, medical grade cyanoacrylate, medical grade silicone adhesive, or combinations thereof.

[0081] Embodiment 35. The punctal plug of any one of embodiments 1-34, wherein the punctal plug does not comprise a reservoir.

[0082] Embodiment 36. The punctal plug of embodiment 35, wherein the reservoir is a tear reservoir or an active agent reservoir.

[0083] Embodiment 37. A method, comprising: inserting the punctal plug of any one of embodiments 1-36 into a punctum of a subject in need thereof, wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, thereby treating the subject in need thereof suffering from the ocular disease or condition.

[0084] Embodiment 38. A method, comprising: inserting the punctal plug of any one of embodiments 15-36 into a punctum of a subject in need thereof, wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, wherein the polymer portion (A) comprises an impermeable material (or an essentially impermeable material); releasing the active agent from an exposed portion of the composite portion (B) towards the punctal opening, thereby treating the subject in need thereof suffering from the ocular disease or condition.

[0085] Embodiment 39. The method of embodiment 38, wherein the releasing of active agent occurs through the head (Bl) of the composite portion.

[0086] Embodiment 40. The method of any one of embodiments 37-39, wherein the ocular disease or condition, or symptom thereof, is selected from the group consisting of: dry eye disease (Keratoconjunctivitis sicca (KCS); Stevens-Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; increased or high intraocular pressure; punctal stenosis; ocular hypertension; and any combinations thereof.

[0087] As various changes can be made in the above -de scribed subject matter without departing from the scope and spirit of the present disclosure, it is intended that all subject matter contained in the above description, or defined in the appended claims, be interpreted as descriptive and illustrative of the present disclosure. Many modifications and variations of the present disclosure are possible in light of the above teachings. Accordingly, the present description is intended to embrace all such alternatives, modifications and variances which fall within the scope of the appended claims.

[0088] All documents cited or referenced herein and all documents cited or referenced in the herein cited documents, together with any manufacturer's instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated by reference, and may be employed in the practice of the disclosure.

Claims

CLAIMSWhat is claimed is:

1. A punctal plug, comprising:(a) a polymer portion (A), wherein the polymer portion comprises a dome (Al), wherein the dome (Al) comprises a cavity (A2), wherein the cavity comprises a cylindrical tunnel (A3) and a base opening at a distal end (A4), wherein the base opening has a diameter greater than a diameter of the cylindrical tunnel; and(b) a composite portion (B), wherein the composite portion comprises a head (B 1) connected to a shaft (B2) connected to a base at a distal end (B3), wherein the composite portion (b) is connected to the polymer portion (a), wherein the base (B3) and a portion of the shaft (B2) of the composite portion (b) are configured to insert into the cavity (A2) of the polymer portion (a), wherein the dimensions of the cavity (A2) is less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2).

2. The punctal plug of claim 1, wherein the polymer portion (A) comprises a flexible, chemically inert polymer.

3. The punctal plug of claim 2, wherein the polymer is selected from the group consisting of: silicone, silicone -based polymer, polyacrylate, polyurethane, and combinations / blends thereof.

4. The punctal plug of any one of claims 1-3, wherein the polymer portion (A) comprises an impermeable material (or an essentially impermeable material).

5. The punctal plug of any one of claims 1-4, wherein the dome (Al) comprises a flat-bottom or a rounded dome shape; wherein the head (Bl) of the composite portion (B) is essentially perpendicular to the shaft (B2); or wherein the head (B 1) of the composite portion (B) is positioned at an angle as compared to the shaft (B2).

6. The punctal plug of any one of claims 1-5,wherein the flat bottom comprises a length of 0.1 mm or greater (e.g., 0.3; 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.1 mm - 2 mm (e.g., 0.2 mm - 1.9 mm; 0.3 mm - 1.8 mm; 0.4 mm - 1.7 mm; 0.5 mm - 1.6 mm; 0.6 mm - 1.5 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm); wherein the polymer portion (A) comprises a diameter (e.g., at its widest point) of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm- 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1. 1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm); wherein the polymer portion (A) comprises a height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm - 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm); wherein the cylindrical tunnel (A3) comprises a diameter of 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.1 mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm - 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm); wherein the cylindrical tunnel (A3) comprises a height of 0.1 mm or greater (e.g., 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5); 1.55 mm or less (e.g., 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.1 mm - 1.55 mm (e.g., 0.15 mm - 1.5 mm; 0.2 mm - 1.45 mm; 0.25 mm - 1.4 mm; 0.3 mm - 1.35 mm; 0.35 mm - 1.3 mm; 0.4 mm - 1.25 mm; 0.45 mm - 1.2 mm; 0.5 mm - 1.15 mm; 0.55 mm - 1.1 mm; 0.6 mm - 1.05 mm; 0.65 mm - 1 mm; 0.7 mm- 0.95 mm; 0.75 mm - 0.9 mm; 0.8 mm - 0.85 mm);wherein the base opening (A4) comprises a diameter of 0.3 mm or greater (e.g., 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9; 2.1; 2.3; 2.5); 2 mm or less (e.g., 1.8; 1.6; 1.4; 1.2; 1; 0.8; 0.6; 0.4; 0.2); or 0.3 mm - 2 mm (e.g., 0.4 mm - 1.9 mm; 0.5 mm - 1.8 mm; 0.6 mm - 1.7 mm; 0.7 mm - 1.6 mm; 0.8 mm - 1.5 mm; 0.9 mm - 1.4 mm; 1 mm - 1.3 mm; 1.1 mm - 1.2 mm); wherein the base opening (A4) comprises a height of 0.05 mm or greater (e.g., 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5); 2 mm or less (e.g., 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.05 mm - 2 mm (e.g., 0.1 mm - 1.95 mm; 0.15 mm - 1.9 mm; 0.2 mm - 1.85 mm; 0.25 mm - 1.8 mm; 0.3 mm - 1.75 mm; 0.7 mm - 1.4 mm; 0.8 mm - 1.3 mm; 0.9 mm - 1.2 mm; 1 mm - 1.1 mm); or any combinations thereof; wherein the angle comprises 90° or greater (e.g., 91; 92; 93; 94; 95; 96; 97; 98; 99; 100; 101; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125); 120.5° or less (e.g., 119.5; 118.5; 117.5; 116.5; 115.5; 114.5; 113.5; 112.5; 111.5; 110.5; 109.5; 108.5; 107.5; 106.5; 105.5; 104.5; 103.5; 102.5; 101.5; 100.5; 99.5; 98.5; 97.5; 96.5; 95.5; 94.5; 93.5; 92.5; 91.5; 90.5; 89.5; 88.5; 87.5; 86.5; 85.5); or 90° - 120.5° (e.g., 90.5° - 120°; 91° - 119.5°; 91.5° - 119°; 92° - 118.5°; 92.5° - 118°; 93° - 117.5°; 93.5° - 117°; 94° - 116.5°; 94.5° - 116°; 95° - 115.5°; 95.5° - 115°; 96° - 114.5°; 96.5° - 114°; 97° - 113.5°; 97.5° - 113°; 98° - 112.5°; 98.5° - 112°; 99° - 111.5°; 99.5° - 111°; 100° - 110.5°; 101.5° - 110°; 102° - 109.5°; 102.5° - 109°; 103° - 108.5°; 103.5° - 108°; 104° - 107.5°; 104.5° - 107°; 105° - 106.5°; 105.5° - 106°); or any combination thereof.

7. The punctal plug of any one of claims 1-6, wherein the composite portion comprises: a binder; an absorbent material; and optionally, an active agent or combinations thereof.

8. The punctal plug of claim 7, wherein the binder comprises epoxy; wherein the absorbent material comprises fumed silica, hydroxypropyl methylcellulose (HPMC)-based polymer, or any combinations or blends thereof; or wherein the active agent comprises an active agent for treating an ocular disease or condition or combinations thereof.

9. The punctal plug of claim 8, wherein the active agent is selected from the group consisting of: prostaglandin analogs (e.g., bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod); antibiotics (e.g., fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline); macrolides (e.g., 12-membered (e.g., methymycin); 14- membered (e.g., clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin); 15 -membered (e.g., azithromycin); 16-membered (e.g., miokamycin,rokitamycin, tilmicosin); ketolides (e.g., telithromycin, cethromycin, solithromycin)); immunosupressants (e.g., tacrolimus, pimecrolimus, sirolimus, cyclosporine); corticosteroids (e.g., dexamethasone; ceftazidime)); beta-blockers (e.g., timolol, levobunolol, metipranolol, carteolol); antifungals (e.g. polyenes, azoles, allylamines, echinocandins); antihistamines (e.g., cetirizine, desloratadine, diphenhydramine, epinastine, fexofenadine, ketotifen, levocetirizine, olopatadine); antiinflammatory agents (e.g., ketorolac, loteprednol); tear lubricants (e.g., hydroxypropyl cellulose); tear producers (e.g., cholinergics (e.g., pilocarpine, cevimeline)); and any combinations thereof; or wherein the active agent is selected from the group consisting of: bimatoprost, latanoprost, tafluprost, travoprost, travaprost / timolol, netarsudil / latanoprost, latanoprostene bunod; fidaxoamicin, roxithromycin, tetracycline, doxycycline, minocycline; methymycin; clarithromycin, dirithromycin, erythromycin, flurithromycin, lankamycin, oleandomycin, pikromycin; azithromycin; miokamycin, rokitamycin, tilmicosin; telithromycin, cethromycin, solithromycin; tacrolimus, pimecrolimus, sirolimus, cyclosporine; dexamethasone; ceftazidime; hydroxypropyl cellulose; pilocarpine, cevimeline; tacrolimus; and any combinations thereof.

10. The punctal plug of any one of claims 1-9, wherein the head (Bl) comprises a diameter of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4); 2.5 or less (e.g., 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15); or 0.5 mm - 2.5 mm (e.g., 0.55 mm - 2.45 mm; 0.6 mm - 2.4 mm; 0.65 mm - 2.35 mm; 0.7 mm- 2.3 mm; 0.75 mm - 2.25 mm; 0.8 mm - 2.2 mm; 0.85 mm - 2.15 mm; 0.9 mm - 2.1 mm; 0.95 mm - 2.05 mm; 1 mm - 2 mm; 1.05 mm - 1.95 mm; 1.1 mm - 1.9 mm; 1.15 mm - 1.85 mm; 1.2 mm - 1.8 mm; 1.25 mm - 1.75 mm; 1.3 mm - 1.7 mm; 1.35 mm - 1.65 mm; 1.4 mm - 1.6 mm; 1.45 mm - 1.55 mm); wherein the head (Bl) comprises a height of 0.1 mm or greater (e.g., 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39); 0.3 mm or less (e.g., 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04); or 0.1 mm - 0.3 mm (e.g., 0.11 mm - 0.29 mm; 0.12 mm - 0.28 mm; 0.13 mm - 0.27 mm; 0.14 mm - 0.26 mm; 0.15 mm - 0.25 mm; 0.16 mm - 0.24 mm; 0.17 mm - 0.23 mm; 0.18 mm - 0.22 mm; 0.19 mm - 0.21 mm); wherein the shaft (B2) comprises a diameter of 0.3 mm or greater (e.g., 0.32; 0.34; 0.36; 0.38; 0.4; 0.42; 0.44; 0.46; 0.48; 0.5; 0.52; 0.54; 0.56; 0.58; 0.6; 0.62; 0.64; 0.66; 0.68; 0.7; 0.72; 0.74; 0.76; 0.78; 0.8; 0.82; 0.84; 0.86; 0.88; 0.9; 0.92; 0.94; 0.96; 0.98; 1; 1.02; 1.04; 1.06); 1 mm or less (e.g., 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87; 0.85; 0.83; 0.81; 0.79; 0.77; 0.75; 0.73; 0.71; 0.69; 0.67; 0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51; 0.49; 0.47; 0.45; 0.43; 0.41; 0.39; 0.37; 0.35; 0.33; 0.31; 0.29; 0.27; 0.25); or 0.3 mm - 1 mm (e.g., 0.31 - 0.99 mm; 0.32 mm - 0.98 mm; 0.33 mm - 0.97 mm; 0.34- 0.96 mm; 0.35 mm - 0.95 mm; 0.36 mm - 0.94 mm; 0.37 - 0.93 mm; 0.38 mm - 0.92 mm; 0.39 mm- 0.91 mm; 0.4 - 0.9 mm; 0.41 mm - 0.89 mm; 0.42 mm - 0.88 mm; 0.43 mm - 0.87 mm; 0.44 - 0.86 mm; 0.45 mm - 0.85 mm; 0.46 mm - 0.84 mm; 0.47 - 0.83 mm; 0.48 mm - 0.82 mm; 0.49 mm - 0.81mm; 0.5 - 0.8 mm; 0.51 mm - 0.79 mm; 0.52 mm - 0.78 mm; 0.53 mm - 0.77 mm; 0.54 - 0.76 mm; 0.55 mm - 0.75 mm; 0.56 mm - 0.74 mm; 0.57 - 0.73 mm; 0.58 mm - 0.72 mm; 0.59 mm - 0.71 mm; 0.6 - 0.7 mm; 0.61 mm - 0.69 mm; 0.62 mm - 0.68 mm; 0.63 mm - 0.67 mm; 0.64 - 0.66 mm); wherein the shaft (B2) comprises a height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2; 2.1; 2.2; 2.3; 2.4; 2.5; 2.6; 2.7; 2.8; 2.9; 3; 3.1; 3.2; 3.3; 3.4; 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35; 0.25; 0.15; 0.05); or 0.5 mm - 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 0.95 mm - 2.55 mm; 1 mm - 2.5 mm; 1.05 mm - 2.45 mm; 1.1 mm - 2.4 mm; 1.15 mm - 2.35 mm; 1.2 mm - 2.3 mm; 1.25 mm - 2.25 mm; 1.3 mm - 2.2 mm; 1.35 mm - 2.15 mm; 1.4 mm - 2.1 mm; 1.45 mm - 2.05 mm; 1.5 mm - 2 mm; 1.55 mm - 1.95 mm; 1.6 mm - 1.9 mm; 1.65 mm - 1.85 mm; 1.7 mm - 1.8 mm); wherein the base (B3) comprises a diameter of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45;0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79; 0.81;0.83; 0.85; 0.87; 0.89; 0.91; 0.93; 0.95; 0.97; 0.99; 1.01; 1.03; 1.05; 1.07; 1.09; 1.11; 1.13; 1.15; 1.17;1.19; 1.21; 1.23; 1.25; 1.27; 1.29; 1.31); 1 mm or less (e.g., 0.98; 0.96; 0.94; 0.92; 0.9; 0.88; 0.86; 0.84;0.82; 0.8; 0.78; 0.76; 0.74; 0.72; 0.7; 0.68; 0.66; 0.64; 0.62; 0.6; 0.58; 0.56; 0.54; 0.52; 0.5; 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 1 mm (e.g., 0.02 mm - 0.99 mm; 0.03 mm - 0.98 mm; 0.04 mm - 0.97 mm; 0.05 mm - 0.96 mm; 0.06 mm - 0.95 mm; 0.07 mm - 0.94 mm; 0.08 mm - 0.93 mm; 0.09 mm - 0.92 mm; 0.1 mm - 0.91 mm; 0.11 mm - 0.9 mm; 0.12 mm - 0.89 mm; 0.13 mm - 0.88 mm; 0.14 mm- 0.87 mm; 0.15 mm - 0.86 mm; 0.16 mm - 0.85 mm; 0.17 mm - 0.84 mm; 0.18 mm - 0.83 mm; 0.19 mm - 0.82 mm; 0.2 mm - 0.81 mm; 0.21 mm - 0.8 mm; 0.22 mm - 0.79 mm; 0.23 mm - 0.78 mm; 0.24 mm - 0.77 mm; 0.25 mm - 0.76 mm; 0.26 mm - 0.75 mm; 0.27 mm - 0.74 mm; 0.28 mm - 0.73 mm; 0.29 mm - 0.72 mm; 0.3 mm - 0.71 mm; 0.31 mm - 0.7 mm; 0.32 mm - 0.69 mm; 0.33 mm - 0.68 mm; 0.34 mm - 0.67 mm; 0.35 mm - 0.66 mm; 0.36 mm - 0.65 mm; 0.37 mm - 0.64 mm; 0.38 mm - 0.63 mm; 0.39 mm - 0.62 mm; 0.4 mm - 0.61 mm; 0.41 mm - 0.6 mm; 0.42 mm - 0.59 mm; 0.43 mm - 0.58 mm; 0.44 mm - 0.57 mm; 0.45 mm - 0.56 mm; 0.46 mm - 0.55 mm; 0.47 mm - 0.54 mm; 0.48 mm - 0.53 mm; 0.49 mm - 0.52 mm; 0.5 mm - 0.51 mm); wherein the base (B3) comprises a height of 0.01 mm or greater (e.g., 0.03; 0.05; 0.07; 0.09; 0.11; 0.13; 0.15; 0.17; 0.19; 0.21; 0.23; 0.25; 0.27; 0.29; 0.31; 0.33; 0.35; 0.37; 0.39; 0.41; 0.43; 0.45; 0.47; 0.49; 0.51; 0.53; 0.55; 0.57; 0.59; 0.61; 0.63; 0.65; 0.67; 0.69; 0.71; 0.73; 0.75; 0.77; 0.79); 0.5 mm or less (e.g., 0.48; 0.46; 0.44; 0.42; 0.4; 0.38; 0.36; 0.34; 0.32; 0.3; 0.28; 0.26; 0.24; 0.22; 0.2; 0.18; 0.16; 0.14; 0.12; 0.1; 0.08; 0.06; 0.04; 0.02); or 0.01 mm - 0.5 mm (e.g., 0.02 mm - 0.49 mm; 0.03 mm- 0.48 mm; 0.04 mm - 0.47 mm; 0.05 mm - 0.46 mm; 0.06 mm - 0.45 mm; 0.07 mm - 0.44 mm; 0.08 mm - 0.43 mm; 0.09 mm - 0.42 mm; 0.1 mm - 0.41 mm; 0.11 mm - 0.4 mm; 0.12 mm - 0.39 mm;0.13 mm - 0.38 mm; 0.14 mm - 0.37 mm; 0.15 mm - 0.36 mm; 0.16 mm - 0.35 mm; 0.17 mm - 0.34 mm; 0.18 mm - 0.33 mm; 0.19 mm - 0.32 mm; 0.2 mm - 0.31 mm; 0.21 mm - 0.3 mm; 0.22 mm - 0.29 mm; 0.23 mm - 0.28 mm; 0.24 mm - 0.27 mm; 0.25 mm - 0.26 mm); wherein the shaft (B2) and the base (B3) comprise a total height of 0.5 mm or greater (e.g., 0.6; 0.7; 0.8; 0.9; 1; 1.1; 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5); 3 mm or less (e.g., 2.95; 2.85; 2.75; 2.65; 2.55; 2.45; 2.35; 2.25; 2.15; 2.05; 1.95; 1.85; 1.75; 1.65; 1.55; 1.45; 1.35; 1.25; 1.15; 1.05; 0.95; 0.85; 0.75; 0.65; 0.55; 0.45; 0.35); or 0.5 mm- 3 mm (e.g., 0.55 mm - 2.95 mm; 0.6 mm - 2.9 mm; 0.65 mm - 2.85 mm; 0.7 mm - 2.8 mm; 0.75 mm - 2.75 mm; 0.8 mm - 2.7 mm; 0.85 mm - 2.65 mm; 0.9 mm - 2.6 mm; 1 mm - 2.55 mm; 1.05 mm- 2.5 mm; 1.1 mm - 2.45 mm; 1.15 mm - 2.4 mm; 1.2 mm - 2.35 mm; 1.25 mm - 2.3 mm; 1.3 mm - 2.25 mm; 1.35 mm - 2.2 mm; 1.4 mm - 2.15 mm; 1.45 mm - 2.1 mm; 1.5 mm - 2.05 mm; 1.55 mm - 2 mm; 1.6 mm - 1.95 mm; 1.65 mm - 1.9 mm; 1.7 mm - 1.85 mm; 1.75 mm - 1.8 mm); wherein the bottom of the head (Bl) to the bottom of the dome (Al) comprises a total height of 1 mm or greater (e.g., 1.02; 1.04; 1.06; 1.08; 1.1; 1.12; 1.14; 1.16; 1.18; 1.2; 1.22; 1.24; 1.26; 1.28;1.3; 1.32; 1.34; 1.36; 1.38; 1.4; 1.42; 1.44; 1.46; 1.48; 1.5; 1.52; 1.54; 1.56; 1.58; 1.6; 1.62; 1.64; 1.66;1.68; 1.7; 1.72; 1.74; 1.76; 1.78; 1.8; 1.82; 1.84; 1.86; 1.88; 1.9; 1.92; 1.94; 1.96; 1.98; 2; 2.02; 2.04; 2.06; 2.08; 2.1; 2.12; 2.14; 2.16; 2.18; 2.2; 2.22; 2.24; 2.26; 2.28; 2.3; 2.32; 2.34; 2.36; 2.38; 2.4; 2.42;2.44; 2.46; 2.48; 2.5; 2.52; 2.54; 2.56; 2.58; 2.6; 2.62; 2.64; 2.66; 2.68; 2.7; 2.72; 2.74; 2.76; 2.78; 2.8;2.82; 2.84; 2.86; 8.88; 2.9; 2.92; 2.94; 2.96; 2.98; 3; 3.02; 3.04; 3.06; 3.08; 3.1; 3.12; 3.14; 3.16; 3.18; 3.2; 3.22; 3.24; 3.26; 3.28; 3.3; 3.32; 3.34; 3.36; 3.38; 3.4; 3.42; 3.44; 3.46; 3.48; 3.5); 3 mm or less (e.g., 2.99; 2.97; 2.95; 2.93; 2.91; 2.89; 2.87; 2.85; 2.83; 2.81; 2.79; 2.77; 2.75; 2.73; 2.71; 2.69; 2.67;2.65; 2.63; 2.61; 2.59; 2.57; 2.55; 2.53; 2.51; 2.49; 2.47; 2.45; 2.43; 2.41; 2.39; 2.37; 2.35; 2.33; 2.31;2.29; 2.27; 2.25; 2.23; 2.21; 2.19; 2.17; 2.15; 2.13; 2.11; 2.09; 2.07; 2.05; 2.03; 2.01; 1.99; 1.97; 1.95;1.93; 1.91; 1.89; 1.87; 1.85; 1.83; 1.81; 1.79; 1.77; 1.75; 1.73; 1.71; 1.69; 1.67; 1.65; 1.63; 1.61; 1.59;1.57; 1.55; 1.53; 1.51; 1.49; 1.47; 1.45; 1.43; 1.41; 1.39; 1.37; 1.35; 1.33; 1.31; 1.29; 1.27; 1.25; 1.23;1.21; 1.19; 1.17; 1.15; 1.13; 1.11; 1.09; 1.07; 1.05; 1.03; 1.01; 0.99; 0.97; 0.95; 0.93; 0.91; 0.89; 0.87;0.85; 0.83; 0.81; 0.79; 0.77; 0.75; 0.73; 0.71; 0.69; 0.67; 0.0.65; 0.63; 0.61; 0.59; 0.57; 0.55; 0.53; 0.51); or 1 mm - 3 mm (e.g., 1.01 mm - 2.99 mm; 1.02 mm - 2.98 mm; 1.03 mm - 2.97 mm; 1.04 mm - 2.96 mm; 1.05 mm - 2.95 mm; 1.06 mm - 2.94 mm; 1.07 mm - 2.93 mm; 1.08 mm - 2.92 mm; 1.09 mm - 2.91 mm; 1.1 mm - 2.9 mm; 1.11 mm - 2.89 mm; 1.12 mm - 2.88 mm; 1.13 mm - 2.87 mm; 1.14 mm- 2.86 mm; 1.15 mm - 2.85 mm; 1.16 mm - 2.84 mm; 1.17 mm - 2.83 mm; 1.18 mm - 2.82 mm; 1.19 mm - 2.81 mm; 1.2 mm - 2.8 mm; 1.21 mm - 2.79 mm; 1.22 mm - 2.78 mm; 1.23 mm - 2.77 mm; 1.24 mm - 2.76 mm; 1.25 mm - 2.75 mm; 1.26 mm - 2.74 mm; 1.27 mm - 2.73 mm; 1.28 mm - 2.72 mm; 1.29 mm - 2.71 mm; 1.3 mm - 2.7 mm; 1.31 mm - 2.69 mm; 1.32 mm - 2.68 mm; 1.33 mm - 2.67 mm; 1.34 mm - 2.66 mm; 1.35 mm - 2.65 mm; 1.36 mm - 2.64 mm; 1.37 mm - 2.63 mm; 1.38 mm - 2.62 mm; 1.39 mm - 2.61 mm; 1.4 mm - 2.6 mm; 1.41 mm - 2.59 mm; 1.42 mm - 2.58 mm; 1.43 mm - 2.57 mm; 1.44 mm - 2.56 mm; 1.45 mm - 2.55 mm; 1.46 mm - 2.54 mm; 1.47 mm - 2.53mm; 1.48 mm - 2.52 mm; 1.49 mm - 2.51 mm; 1.5 mm - 2.5 mm; 1.51 mm - 2.49 mm; 1.52 mm - 2.48 mm; 1.53 mm - 2.47 mm; 1.54 mm - 2.46 mm; 1.55 mm - 2.45 mm; 1.56 mm - 2.44 mm; 1.57 mm - 2.43 mm; 1.58 mm - 2.42 mm; 1.59 mm - 2.41 mm; 1.6 mm - 2.4 mm; 1.61 mm - 2.39 mm; 1.62 mm - 2.38 mm; 1.63 mm - 2.37 mm; 1.64 mm - 2.36 mm;1.65 mm - 2.35 mm; 1.66 mm - 2.34 mm; 1.67 mm - 2.33 mm; 1.68 mm - 2.32 mm; 1.69 mm - 2.31 mm; 1.7 mm - 2.3 mm; 1.71 mm - 2.29 mm; 1.72 mm - 2.28 mm; 1.73 mm - 2.27 mm; 1.74 mm - 2.26 mm; 1.75 mm - 2.25 mm; 1.76 mm - 2.24 mm; 1.77 mm - 2.23 mm; 1.78 mm - 2.22 mm; 1.79 mm - 2.21 mm; 1.8 mm - 2.2 mm;I.81 mm - 2.19 mm; 1.82 mm - 2.18 mm; 1.83 mm - 2.17 mm; 1.84 mm - 2.16 mm; 1.85 mm - 2.15 mm; 1.86 mm - 2.14 mm; 1.87 mm - 2.13 mm; 1.88 mm - 2.12 mm; 1.89 mm - 2.11 mm; 1.9 mm - 2.1 mm; 1.91 mm - 2.09 mm; 1.92 mm - 2.08 mm; 1.93 mm - 2.07 mm; 1.94 mm - 2.06 mm; 1.95 mm - 2.05 mm; 1.96 mm - 2.04 mm; 1.97 mm - 2.03 mm; 1.98 mm - 2.02 mm; 1.99 mm - 2.01 mm); or any combinations thereof.I I. The punctal plug of any one of claims 1-10, wherein the dimensions of the cylindrical tunnel (A3) and the base opening (A4) are less than the dimensions of the base (B3) and the portion of the shaft (B2) inserted into the cavity (A2).

12. The punctal plug of any one of claims 1-11, wherein an outer surface of the punctal plug or portion thereof comprises a coating, wherein the coating comprises butvar and / or parylene.

13. The punctal plug of any one of claims 1-12, wherein the insertion occurs to insert the composite portion into the polymer portion.

14. The punctal plug of claim 13, wherein the composite portion and the polymer portion are secured together with a biocompatible glue.

15. The punctal plug of claim 14, wherein the biocompatible glue comprises fibrin glue, epoxy resin or adhesive, medical grade cyanoacrylate, medical grade silicone adhesive, or combinations thereof.

16. The punctal plug of any one of claims 1-15, wherein the punctal plug does not comprise a reservoir, wherein the reservoir is a tear reservoir or an active agent reservoir.

17. A method, comprising: inserting the punctal plug of any one of claims 1-16 into a punctum of a subject in need thereof, wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, thereby treating the subject in need thereof suffering from the ocular disease or condition.

18. A method, comprising: inserting the punctal plug of any one of claims 7-16 into a punctum of a subject in need thereof,wherein the subject in need thereof suffers from an ocular disease or condition, or symptom thereof, wherein the polymer portion (A) comprises an impermeable material (or an essentially impermeable material); releasing the active agent from an exposed portion of the composite portion (B) towards the punctal opening, thereby treating the subject in need thereof suffering from the ocular disease or condition.

19. The method of claim 18, wherein the releasing of active agent occurs through the head (Bl) of the composite portion.

20. The method of any one of claims 17-19, wherein the ocular disease or condition, or symptom thereof, is selected from the group consisting of: dry eye disease (Keratoconjunctivitis sicca (KCS)); Stevens-Johnson syndrome; keratoconjunctivitis sicca; contact lens wear; superior limbic keratoconjunctivitis; glaucoma; increased or high intraocular pressure; punctal stenosis; ocular hypertension; and any combinations thereof.

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