Drug delivery implants as intraocular drug depots

Abstract

Disclosed herein are drug delivery implants configured to be implanted into the eye of a subject and serve as intraocular drug depots. The implants reside in an intraocular target site until activation, at which time the implants release the drug (or drugs) housed within the implant in a controlled release fashion. The internal components of the implants can be arranged to control the rate of elution of a drug within an internal reservoir, and can be retained within the implant through the use of various embodiments of retaining elements.

Description

PCT / US25 / 43600 26 August 2025 (26.08.2025)GLAUKO.281WO PATENTDRUG DELIVERY IMPLANTS AS INTRAOCULAR DRUG DEPOTS AND METHODS OF USING SAMEFIELD

[0001] Embodiments of the inventions generally relate to an implantable drug delivery device (e.g., an intraocular implant within the eye) and various methods of assembling and / or using the same.BACKGROUND

[0002] The mammalian eye is a specialized sensory organ capable of light reception and is able to receive visual images. The retina of the eye consists of photoreceptors that are sensitive to various levels of light, interneurons that relay signals from the photoreceptors to the retinal ganglion cells, which transmit the light-induced signals to the brain. The iris is an intraocular membrane that is involved in controlling the amount of light reaching the retina. The iris consists of two layers (arranged from anterior to posterior), the pigmented fibrovascular tissue known as a stroma and pigmented epithelial cells. The stroma connects a sphincter muscle (sphincter pupillae), which contracts the pupil, and a set of dilator muscles (dilator pupillae) which open it. The pigmented epithelial cells block light from passing through the iris and thereby restrict light passage to the pupil.

[0003] Numerous pathologies can compromise or entirely eliminate an individual’s ability to perceive visual images, including trauma to the eye, infection, degeneration, vascular irregularities, and inflammatory problems. The central portion of the retina is known as the macula. The macula, which is responsible for central vision, fine visualization and color differentiation, may be affected by age related macular degeneration (wet or dry), diabetic macular edema, idiopathic choroidal neovascularization, or high myopia macular degeneration, among other pathologies.

[0004] Other pathologies, such as abnormalities in intraocular pressure, can affect vision as well. Aqueous humor is a transparent liquid that fills at least the region between the cornea, at the front of the eye, and the lens and is responsible for producing a pressure within the ocular cavity. Normal intraocular pressure is maintained by drainage of aqueous humor from the anterior chamber by way of a trabecular meshwork which is located in an anterior chamber angle, lying between the iris and the cornea or by way of the “uveoscleral outflow pathway.” The “uveoscleral outflow pathway” is the space orPCT / US25 / 43600 26 August 2025 (26.08.2025) passageway whereby aqueous exits the eye by passing through the ciliary muscle bundles located in the angle of the anterior chamber and into the tissue planes between the choroid and the sclera, which extend posteriorly to the optic nerve. About two percent of people in the United States have glaucoma, which is a group of eye diseases encompassing a broad spectrum of clinical presentations and etiologies but unified by increased intraocular pressure. Glaucoma causes pathological changes in the optic nerve, visible on the optic disk, and it causes corresponding visual field loss, which can result in blindness if untreated. Increased intraocular pressure is a risk factor associated with glaucoma that can be treated. Thus lowering intraocular pressure is a major treatment goal for glaucoma, and can be achieved by drug therapy, surgical therapy, or combinations thereof.

[0005] Many pathologies of the eye progress due to the difficulty in administering therapeutic agents to the eye in sufficient quantities and / or duration necessary to ameliorate symptoms of the pathology. Often, uptake and processing of the active drug component of the therapeutic agent occurs prior to the drug reaching an ocular target site. Due to this metabolism, systemic administration may require undesirably high concentrations of the drug to reach therapeutic levels at an ocular target site. This can not only be impractical or expensive, but may also result in a higher incidence of side effects. Topical administration is potentially limited by limited diffusion across the cornea, or dilution of a topically applied drug by tear-action. Even those drugs that cross the cornea may be unacceptably depleted from the eye by the flow of ocular fluids and transfer into the general circulation.SUMMARY

[0006] Intraocular implants can be implanted within the eye to a target ocular tissue to provide time-released treatment fluids, powders, tablets, gels, drugs, agents, compounds, compositions, mixtures) to the eye as part of a proscribed treatment plan. Typical methods of implantation require relatively invasive surgical procedures, pose a risk of excessive trauma to the eye, and require excessive handling of the implant. For example, in a typical method of implantation, an incision would be made into the eye, and a surgical tool would either be inserted into the incision or the incision would be widened to accommodate the implant end of the tool, which could cause further trauma to the eye. Advantageously, a surgical procedure and tool as outlined herein could avoid some or all of these issues. A means for ocular administration of a therapeutic agent in a controlled and targeted fashion would address the limitations of other delivery routes.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0007] Various embodiments disclosed herein can relate to a drug delivery ocular implant. The drug delivery ocular implant can include an outer shell or body. The outer shell can have a proximal end and a distal end. The outer shell can be shaped to define an interior chamber. The proximal end of the outer shell can be configured to reversibly interact with an implantation device. The ocular implant can include a drug positioned within the interior chamber. The ocular implant can include a drug release element, such as a permeable membrane, which can be configured to release the drug from the interior chamber upon exposure to a stimulus. This drug release element can be positioned within the interior chamber by positioning elements. The positioning elements can selectively deform a portion of the drug release element to more precisely control a drug elution rate from the implant. The drug release element and the positioning elements can be retained within the interior chamber by a retaining member. The retaining member can interface with features, notches, or openings in the main body proximal to the opening. These features can either interface with the retaining member immediately after the retaining member is installed, or can be deformed to interface with the retaining member. Alternatively or in addition to this, the retaining member can partially deform to connect with the interface members. The ocular implant can include an anchor. The anchor can be configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

[0008] According to some embodiments, the techniques or aspects described herein relate to an implant configured to be implanted in an eye to treat an ocular disorder, the implant including: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of crimping portions; a drug (e.g., travoprost) positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate; one or more positioning elements configured to position the drug release element, and a retaining element with one or more openings; wherein, when the drug is positioned within the internal reservoir, the one or more positioning elements are inserted into the opening in the proximal end with the drug release element; wherein, when the one or more positioning elements and the drug release element are arranged within the main body, the retaining element is inserted into the opening in the proximal end to form an assembly within the main body; wherein the assembly is compressed such that the plurality of crimping portions impede movement of the assembly from the main body; wherein the drug elutes from thePCT / US25 / 43600 26 August 2025 (26.08.2025) implant by passing through the drug release element and the one or more openings in the retaining element.

[0009] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the main body further includes an interface feature, wherein the implant is configured to be positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

[0010] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the distal end of the main body includes an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue (e.g., trabecular meshwork, sclera, conjunctiva, scleral spur, choroid, etc.) and stably retain the implant at the target ocular tissue.

[0011] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the main body.

[0012] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the retaining element.

[0013] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the drug release element includes an undeformed portion and a deformed portion (e.g., compressed portion), the deformed portion being compressed by the one or more positioning elements, wherein the drug elutes from the implant by passing through the undeformed portion of the drug release element.

[0014] According to some embodiments, the techniques or aspects described herein relate to an implant configured to be implanted in an eye to treat an ocular disorder, the implant including: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of crimping portions; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate, and a retaining element with one or more openings; wherein, when the drug, the drug release element, and the retaining element are inserted into the opening in the main body, the plurality of crimping portions are configured to be selectively deformed to impede movement of the drug release element and the retaining element from the main body.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0015] According to some embodiments, the techniques or aspects described herein relate to an implant, further including one or more positioning elements configured to position the drug release element within the opening in the main body.

[0016] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the main body.

[0017] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the retaining element.

[0018] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the main body further includes an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

[0019] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the distal end of the main body includes an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

[0020] According to some embodiments, the techniques or aspects described herein relate to an implant configured to be implanted in an eye to treat an ocular disorder, the implant including: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retention reliefs (e.g., openings, grooves, ridges, holes, apertures); a drug (e.g., travoprost) positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate; one or more positioning elements configured to position the drug release element, and a retaining element, the retaining element including one or more flexible retention features and one or more fluid passages, the one or more fluid passages allowing fluid flow around the retaining element; wherein, when the drug is positioned within the internal reservoir, the one or more positioning elements are inserted into the opening in the proximal end with the drug release element; wherein, when the one or more positioning elements and the drug release element are arranged within the main body, the retaining element is installed into the main body; wherein installation of the retaining element includes: inserting a first portion of the retaining element into a first opening of the plurality of retention reliefs (e.g., retention openings); selectively deforming the retaining element to have a cross-sectional profilePCT / US25 / 43600 26 August 2025 (26.08.2025) smaller than the cross-sectional profile of the opening; aligning a second portion of the retaining element with a second opening of the plurality of retention reliefs (e.g., retention openings), and allowing the retaining element to return to an undeformed state by releasing compression on the retaining element, wherein allowing the retaining element to return to an undeformed state inserts the second portion of the retaining element into the second opening of the plurality of retention reliefs (e.g., retention openings); wherein the drug elutes, or is configured to elute, from the implant by passing through the drug release element and around the retaining element.

[0021] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the plurality of retention reliefs (e.g., retention openings) include holes passing through the proximal end of the main body. In some configurations, the retaining element has a cross-sectional profile larger than a cross- sectional profile of the opening to the internal reservoir.

[0022] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the one or more flexible retention features deform as the retaining element is installed, the one or more flexible retention features configured to assist in aligning the retaining element within the main body.

[0023] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the main body further includes an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

[0024] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the distal end of the main body includes an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

[0025] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the main body.

[0026] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the retaining element.

[0027] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the drug release element includes an uncompressed portion and a compressed portion, the compressed portion being compressed by the one orPCT / US25 / 43600 26 August 2025 (26.08.2025) more positioning elements, wherein the drug elutes from the implant by passing through the uncompressed portion of the drug release element.

[0028] In accordance with several embodiments, an implant configured to be implanted in an eye to treat an ocular disorder includes a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retention reliefs. The implant further includes a drug (e.g., travoprost) positioned within the internal reservoir. The implant further includes a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid (e.g., aqueous humor) at a release rate or elution rate. The implant further includes one or more positioning elements configured to position the drug release element and a retaining element, the retaining element comprising one or more flexible retention features and one or more fluid passages (e.g., pores, openings, apertures), the one or more fluid passages allowing fluid flow around the retaining element.

[0029] When the drug is positioned within the internal reservoir (e.g., upon manufacturing or assembly), the one or more positioning elements may be inserted into the opening in the proximal end with the drug release element. When the one or more positioning elements and the drug release element are arranged within the main body (e.g., upon manufacturing or assembly), the retaining element may be installed into the main body.

[0030] The retaining element may comprise a first portion of the retaining element aligned with a first opening of the plurality of retention reliefs and a a selectively flexible retaining element (e.g., retaining element portion) having a cross-sectional profile smaller than the cross-sectional profile of the opening in the proximal end. A second portion of the retaining element may be aligned with a second opening of the plurality of retention reliefs. The retaining element can be configured to return to an unflexed or less flexed state by releasing compression on at least a portion of the retaining element. The drug may be configured to elute from the implant by passing through the drug release element and around at least a portion of the retaining element.

[0031] In some configurations, allowing the retaining element to return to an unflexed or less flexed state allows the second portion of the retaining element to be inserted into the second opening of the plurality of retention reliefs.

[0032] In some configurations, the plurality of retention reliefs comprise holes passing through the proximal end of the main body. The retention reliefs may comprise one or more of openings, grooves, or ridges.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0033] In some configurations, the one or more flexible retention features deform as the retaining element is installed, the one or more flexible retention features configured to assist in aligning the retaining element within the main body.

[0034] In some configurations, the main body further includes an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

[0035] In some configurations, the distal end of the main body includes an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

[0036] In some configurations, at least one of the one or more positioning elements are integrally formed with the main body.

[0037] In some configurations, at least one of the one or more positioning elements are integrally formed with the retaining element.

[0038] In some configurations, the retaining element comprises a cross- sectional profile larger than a cross-sectional profile of the opening to the internal reservoir.

[0039] In some configurations, the drug release element comprises an uncompressed portion and a compressed portion, the compressed portion being compressed by the one or more positioning elements, wherein the drug elutes, or is configured to elute, from the implant by passing through the uncompressed portion of the drug release element.

[0040] In some configurations, the internal reservoir has a volume between 100 nL to 500 nL (e.g., between 100 nL to 300 nL, between 150 nL and 450 nL, between 200 nL and 400 nL, between 250 nL and 500 nL, overlapping ranges thereof, or any value within the recited ranges).

[0041] In some configurations, the drug has a release rate or elution rate between 25 ng / day to 250 ng / day (e.g., between 25 ng / day to 100 ng / day, between 50 ng / day to 150 ng / day, between 100 ng / day to 250 ng / day, between 25 ng / day to 150 ng / day, overlapping ranges thereof, or any value within the recited ranges).

[0042] According to some embodiments, the techniques or aspects described herein relate to an implant configured to be implanted in an eye to treat an ocular disorder, the implant including: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retaining features; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate, and a flexible retaining element with one or more fluid passages; wherein, when the drug, the drug releasePCT / US25 / 43600 26 August 2025 (26.08.2025) element, and the flexible retaining element are inserted into the opening in the main body, the flexible retaining element is configured to deform and interface with the plurality of retaining features in the main body to impede movement of the drug release element and the flexible retaining element from the main body.

[0043] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein installation of the flexible retaining element includes: inserting a first portion of the flexible retaining element into a first opening of the plurality of retaining features; selectively deforming the flexible retaining element to have a cross- sectional profile smaller than the cross-sectional profile of the opening; aligning a second portion of the flexible retaining element with a second opening of the plurality of retaining features; and allowing the flexible retaining element to return to an undeformed state by releasing compression on the flexible retaining element, wherein allowing the flexible retaining element to return to an undeformed state inserts the second portion of the flexible retaining element into the second opening of the plurality of retaining features.

[0044] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the drug elutes from the implant by passing through the drug release element and around the flexible retaining element. The drug may be eluted from a proximal end of the implant, a distal end of the implant, and / or along any portion of the main body of the implant.

[0045] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the plurality of retaining features include holes passing through the proximal end of the main body.

[0046] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the flexible retaining element further includes one or more flexible retention features, wherein the one or more flexible retention features deform as the flexible retaining element is installed, the one or more flexible retention features configured to assist in aligning the flexible retaining element within the main body.

[0047] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the main body further includes an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

[0048] According to some embodiments, the techniques or aspects described herein relate to an implant, further including one or more positioning elements configured to position the drug release element within the opening in the main body.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0049] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the main body.

[0050] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein one of the one or more positioning elements is integrally formed with the flexible retaining element.

[0051] According to some embodiments, the techniques or aspects described herein relate to an implant, wherein the distal end of the main body includes an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

[0052] According to some embodiments, the techniques or aspects described herein relate to a method of assembling an implant configured to treat an ocular disorder, the method including: obtaining a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retention elements, the distal end having an implant connection end; providing a drug to the internal reservoir; positioning one or more positioning elements in the opening in the proximal end with a drug release element, such that the one or more positioning elements are contacting the drug release element; positioning a retaining element in the opening in the proximal end adjacent a positioning element; compressing the one or more positioning elements, the drug release element, and the retaining element such that a proximal most surface of the retaining element is below a distal most surface of the plurality of retention elements; and retaining the one or more positioning elements, the drug release element, and the retaining element to the main body.

[0053] According to some embodiments, the techniques or aspects described herein relate to a method, wherein retaining the one or more positioning elements, the drug release element, and the retaining element to the main body includes deforming the proximal end adjacent the plurality of retention elements to reduce a size of the opening such that the retaining element cannot exit the opening.

[0054] According to some embodiments, the techniques or aspects described herein relate to a method, wherein retaining the one or more positioning elements, the drug release element, and the retaining element to the main body includes: inserting a first portion of the retaining element into a first portion of the plurality of retention elements; selectively deforming the retaining element to have a cross-sectional profile smaller than a cross-sectional profile of the opening; aligning a second portion of the retaining elementPCT / US25 / 43600 26 August 2025 (26.08.2025) with a second portion of the plurality of retention elements; and allowing the retaining element to return to an undeformed state by releasing compression on the retaining element, wherein allowing the retaining element to return to the undeformed state inserts the second portion of the retaining element into the second portion of the plurality of retention elements.PCT / US25 / 43600 26 August 2025 (26.08.2025)BRIEF DESCRIPTION OF THE DRAWINGS

[0055] These and other features, aspects, and advantages of the present disclosure will now be described with reference to the drawings of embodiments or examples of the invention, which embodiments or examples are intended to illustrate and not to limit the scope of the disclosure.

[0056] Figure 1 A is a schematic cross-sectional view of an eye.

[0057] Figure IB is an enlarged cross-sectional view of an anterior chamber angle of the eye of Figure 1A.

[0058] Figure 2A is a right side perspective view of an implant according to one embodiment or example of the present application.

[0059] Figure 2B is a side view illustrating the implant of Figure 2A.

[0060] Figure 2C is a side cross-sectional view illustrating the implant of Figure2A.

[0061] Figure 2D is a side view illustrating the implant of Figure 2A.

[0062] Figure 2E is a right side perspective deconstructed view illustrating the implant of Figure 2 A.

[0063] Figure 3A is a right side perspective view of an implant according to one embodiment of the present application.

[0064] Figure 3B is a right side perspective deconstructed view of the implant of Figure 3 A.

[0065] Figure 3C is a side cross-sectional view illustrating the implant of Figure 3A.

[0066] Figure 3D is a side cross-sectional view illustrating the proximal end of the implant of Figure 3A.

[0067] Figure 3E is a side cross-sectional view illustrating a proximal portion of a main body of an implant according to one embodiment or example of the present application.

[0068] Figure 3F is a side cross-sectional view illustrating a proximal portion of a main body of an implant according to one embodiment or example of the present application.

[0069] Figure 3G is a right side perspective view of an implant according to one embodiment or example of the present application.

[0070] Figure 4A is a right side perspective view of an implant according to one embodiment or example of the present application.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0071] Figure 4B is a right side perspective deconstructed view of the implant of Figure 4 A.

[0072] Figure 4C is a side cross-sectional view illustrating the implant of Figure 4A.

[0073] Figure 4D is a top view of an implant according to one embodiment or example of the present application.

[0074] Figure 4E is a perspective view of an implant during its assembly process according to one embodiment or example of the present application.

[0075] Figure 4F is a perspective view of an implant according to one embodiment or example of the present application.

[0076] Figure 5A is a right side perspective view of an implant according to one embodiment or example of the present application.

[0077] Figure 5B is a side cross-sectional view illustrating the implant of Figure 5A.

[0078] Figure 5C is a side cross-sectional view illustrating the implant of Figure 5A.

[0079] Figure 5D is a top cross-sectional view illustrating the implant of Figure 5A.

[0080] Figure 6A is a right side perspective view of an implant according to one embodiment or example of the present application.

[0081] Figure 6B is a side cross-sectional view illustrating the implant of Figure 6A.

[0082] Figure 6C is a side cross-sectional view illustrating the implant of Figure 6A.

[0083] Figure 6D is a top cross-sectional view illustrating the implant of Figure 6A.

[0084] Figure 7A is a right side perspective view of an implant according to one embodiment or example of the present application.

[0085] Figure 7B is a side cross-sectional view illustrating the implant of Figure 7A.

[0086] Figure 7C is a bottom perspective view illustrating the implant of Figure 7A.

[0087] Figure 7D is a perspective view illustrating the implant of Figure 7A.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0088] Figure 8A is a right side perspective view of an implant according to one embodiment or example of the present application.

[0089] Figure 8B is a side cross-sectional view illustrating the implant of Figure8A.

[0090] Figure 8C is a side cross-sectional view illustrating an implant according to one embodiment or example of the present application.

[0091] Figure 9A a right side perspective view of an implant according to one embodiment or example of the present application.

[0092] Figure 9B is a right side perspective deconstructed view illustrating the implant of Figure 9A.

[0093] Figure 10A a right side perspective view of an implant according to one embodiment or example of the present application.

[0094] Figure 10B is a right side perspective deconstructed view illustrating the implant of Figure 10 A.

[0095] Figure 11A illustrates a unitary combined retainer spacer according to various embodiments or examples of the present application.

[0096] Figure 1 IB is a perspective view of a retainer spacer in accordance with an embodiment or example of the present application.

[0097] Figure 12 illustrates another drug delivery implant incorporating inflow and outflow pathways to facilitate shunting or drainage of aqueous humor through the implant, which feature may be incorporated with any of the figures or examples disclosed herein.PCT / US25 / 43600 26 August 2025 (26.08.2025)DETAILED DESCRIPTIONIntroduction

[0098] Achieving local ocular administration of a drug may require direct injection or application, but could also include the use of a drug eluting implant or other drug delivery device, a portion of which, could be positioned in close proximity to the target site of action within the eye or within the chamber of the eye where the target site is located (e.g., anterior chamber, posterior chamber, or both simultaneously). Use of a drug eluting implant or other drug delivery device could also allow the targeted delivery of a drug to a specific ocular tissue, such as, for example, the macula, the retina, the ciliary body, the optic nerve, or the vascular supply to certain regions of the eye. Use of a drug eluting implant or other drug delivery device could also provide the opportunity to administer a controlled amount of drug for a desired amount of time, depending on the pathology. For instance, some pathologies may require drugs to be released at a constant rate for just a few days, others may require drug release at a constant rate for up to several days, weeks, or months, still others may need periodic or varied release rates over time, and even others may require periods of no release (e.g., a “drug holiday”). Further, implants may serve additional functions once the delivery of the drug is complete. Implants may maintain the patency of a fluid flow passageway within an ocular cavity (e.g., function as a stent), they may function as a reservoir for future administration of the same or a different therapeutic agent, or may also function to maintain the patency of a fluid flow pathway or passageway from a first location to a second location (e.g., between a chamber of the eye and a physiologic outflow pathway, such as Schl emm’s canal or a uveoscleral outflow pathway), so as to function as a shunt or conduit. Conversely, should a drug be required only acutely, an implant may also be made completely biodegradable.

[0099] Implants according to several embodiments disclosed herein advantageously do not require an osmotic or ionic gradient to release the drug(s), are implanted with a device that minimizes trauma to the healthy tissues of the eye which thereby reduces ocular morbidity, and / or may be used to deliver one or more drugs in a targeted and controlled release fashion to treat multiple ocular pathologies or a single pathology and its symptoms. However, in certain embodiments, an osmotic or ionic gradient is used to initiate, control (in whole or in part), or adjust the release of a drug (or drugs) from an implant. In some embodiments, osmotic pressure is balanced between the interior portion(s) of the implant and the ocular fluid, resulting in no appreciable gradientPCT / US25 / 43600 26 August 2025 (26.08.2025)(either osmotic or ionic). In such embodiments, variable amounts of solute are added to the drug within the device in order to balance the pressures.

[0100] As used herein, “drug” refers generally to one or more drugs that may be administered alone, in combination and / or compounded with one or more pharmaceutically acceptable excipients (e.g. binders, disintegrants, fillers, diluents, lubricants, drug release control polymers or other agents, etc.), auxiliary agents or compounds as may be housed within the implants as described herein. The term “drug” is a broad term that may be used interchangeably with “therapeutic agent” and “pharmaceutical” or “pharmacological agent” or “active pharmaceutical ingredient” and includes not only so-called small molecule drugs, but also macromolecular drugs, and biologies, including but not limited to peptides, proteins, nucleic acids, antibodies, DARPins, and the like including their derivatives, regardless of whether such drug is natural, synthetic, or recombinant. Drug may refer to the drug alone or in combination with the excipients described above. “Drug” may also refer to an active drug itself or a prodrug or salt of an active drug.

[0101] In some embodiments, the drug can include one or more glaucoma drugs. The glaucoma drug can be an intraocular pressure lowering drug and include one or more of a prostaglandin analog (e.g., latanoprost, travoprost, bimatoprost, unoprostone), a prostaglandin (e.g., prostaglandin F2 alpha), a prostaglandin precursors, a beta-blocker agent (e.g. atenolol propranolol, metipranolol, betaxolol, carteolol, levobetaxolol, levobunolol, timolol), a carbonic anhydrase inhibitors (e.g., dorzolamide, bnnzolamide), an alpha-adrenergic agonists (e.g., brimonidine, apraclonidine), a Rho-kinase (ROCK) inhibitor (e.g., netarsudil, ripasudil), an acetylcholinesterase inhibitor (e.g., donepezil, physostigmine, rivastigmine), an E-prostanoid subtype 2 (EP2) agonist (e.g., taprenepag isopropyl, aganepag isopropyl, omidenepag isopropyl), or a miotic (e.g., pilocarpine). In some embodiments, the drug includes more than one glaucoma drugs where each glaucoma drug has a different mode of action. For example, one of the drugs may reduce intraocular pressure by reducing aqueous humor production and another one of the drugs may lower intraocular pressure by increasing aqueous humor outflow through one or both of uveoscleral or trabecular meshwork pathways).

[0102] In some embodiments, the drug can include one or more drugs for treating retinal disease. The retinal disease drug can include an anti-vascular endothelial growth factor (anti-VEGF) drug (e.g. ranibizumab, bevacizumab, aflibercept,PCT / US25 / 43600 26 August 2025 (26.08.2025) brolucizumab, faricimab-svoa), DARPin engineered to target vascular endothelial growth factor (VEGF), another biologic that inhibits Angiopoietin-2, an IL-6 inhibitor (e.g., tocilizumab, sarilumab, pacibekitug), and IL- 17 inhibitor (e.g., secukinumab, ixekizumab, bimekizumab, sonellamab), aTie-2 activator (e.g., AKB-9778, AXT107), atyrosine kinase inhibitor (e.g., axitinib, cediranib, fruquintinib, lenvatinib, nintedanib, pazopanib, regorafenib, semaxanib, sorafenib, sunitinib, tivozanib, toceranib, vandetanib), a complement cascade inhibitors (pegcetacoplan, avacincaptad pegol), or a glucocorticoid or corticosteroid (e.g., betamethasone, cortisone, dexamethasone, dexamethasone 21- phosphate, methylprednisolone, prednisolone 21 -phosphate, prednisolone acetate, prednisolone, fluroometholone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, triamcinolone acetonide, beclomethasone, budesonide, flunisolide, fluoromethoIone, fluticasone, hydrocortisone, hydrocortisone acetate, loteprednol, rimexolone). It is to be understood that, in some embodiments, these drugs may be used for treating disorders in non-retinal tissue. In some embodiments, the drug includes more than one retinal disease drugs where each retinal disease drug has a different mode of action. For example, the drug may include a tyrosine kinase inhibitor and an anti-VEGF drug.

[0103] In some embodiments, the drug can include one or more drugs for treating comeal tissue. The comeal tissue drug can include a cholinergic agonist (e.g., pilocarpine), an acetylcholinesterase inhibitor (e.g., donepezil, physostigmine, rivastigmine), an anti-infective or antimicrobial agent (e.g., bacitracin, tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxy tetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodium propionate), an aminoglycosides (e.g., gentamicin and tobramycin) a fluoroquinolone (e.g., ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin), an antifungal (e.g., amphotericin B and miconazole) antivirals (e.g., idoxuridine trifluorothymidine, acyclovir, ganciclovir), an interferon, antimicotics, an anti-inflammatory (e.g., a corticosteroid, ketorolac, diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, ketorolac, salicylate, indomethacin, naxopren, piroxicam and nabum. etone). It is to be understood that, in some embodiments, these drugs may be used for treating disorders in non-comeal tissue.

[0104] In some embodiments, the drug can include one or more of a mydriatic- cycloplegic agent (e.g., atropine, cyclopentolate, succinylcholine, homatropine,PCT / US25 / 43600 26 August 2025 (26.08.2025) phenylephrine, scopolamine, tropicamide), an anti-histamine (e.g., ketotifen, olopatadine, cetirizine, lastacraft, elastine, emedastine and levocabastine),

[0105] In some embodiments, the drug may include one or more of immune- modulating agents such as antiallergenics, including, for example, sodium cromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine, pyrilamine, prophenpyridamine; anti-histamine agents such as azelastine, emedastine and levocabastine; immunological drugs (such as vaccines, immune stimulants, and / or immunosuppressants); MAST cell stabilizer agents such as cromolyn sodium, ketotifen, lodoxamide, nedocrimil, olopatadine and pemirolastciliary body ablative agents, such as gentimicin and cidofovir; and other ophthalmic agents such as verteporfin, proparacaine, tetracaine, cyclosporine and pilocarpine; inhibitors of cell-surface glycoprotein receptors; decongestants such as phenylephrine, naphazoline, tetrahydrazoline; lipids or hypotensive lipids; dopaminergic agonists and / or antagonists such as quinpirole, fenoldopam, and ibopamine; vasospasm inhibitors; vasodilators; antihypertensive agents; angiotensin converting enzyme (ACE) inhibitors; angiotensin-1 receptor antagonists such as olmesartan; microtubule inhibitors; molecular motor (dynein and / or kinesin) inhibitors; actin cytoskeleton regulatory agents such as cyctchalasin, latnmculin, swinholide A, ethacrynic acid, H-7, and Rho-kinase (ROCK) inhibitors; remodeling inhibitors; modulators of the extracellular matrix such as tert-butylhydro-quinolone and AL-3037A; adenosine receptor agonists and / or antagonists such as N-6-cylclophexyladenosine and (R)-phenylisopropyladenosine; serotonin agonists; hormonal agents such as estrogens, estradiol, progestational hormones, progesterone, insulin, calcitonin, parathyroid hormone, peptide and vasopressin hypothalamus releasing factor; growth factor antagonists or growth factors, including, for example, epidermal growth factor, fibroblast growth factor, platelet derived growth factor or antagonists thereof, transforming growth factor beta, somatotrapin, fibronectin, connective tissue growth factor, bone morphogenic proteins (BMPs); cytokines such as interleukins, CD44, cochlin, and serum amyloids, such as serum amyloid A.

[0106] In some embodiments, the drug can include one or more drugs targeting one or more diseases or anatomies. In some embodiments, the drug can include a first drug for treating retinal disease and a second drug for treating comeal disease. In some embodiments, the drug can include a first drug for lower intraocular pressure and a second drug to treat age-related macular degeneration. In some embodiments, the drug includes two or more types of drugs that are homogenously distributed in the implants described below; in such embodiments, the tw o or more drugs may elute together over the lifetime ofPCT / US25 / 43600 26 August 2025 (26.08.2025) the implant. In some embodiments, the drug includes a core of a first drug surrounded by second drug; in such embodiments, the second drug may begin to elute before the first drug when the implant is implanted in the eye. In some embodiments, drugs may be located in separate chambers as described below with reference to implants having multiple chambers (e.g., those shown in Figures 5A-6D). In some embodiments, the drug can include a first drug and a second drug, where the implant, when implanted at a target tissue, elutes the first drug for a first period of time (e.g., three or more months, three months to 12 months, more than 12 months, or up to 36 months) and the second drug elutes for a second period of time (e.g., less than one month, less than one week, less than three days, less than one day) that is substantially shorter than the first period of time.

[0107] In several embodiments, the drug release element can comprise a membrane that seals the interior chamber off from the intraocular environment until the drug release element is exposed to the stimulus. In several embodiments, the membrane comprises one or more of gold foil, silver foil, titanium foil, platinum foil, rhodium foil, tungsten foil, stainless steel foil, steel foil, nitinol foil, pary lene, and nylon foil.

[0108] As used herein, “patient” shall be given its ordinary meaning and shall also refer to mammals generally. The term “mammal”, in turn, includes, but is not limited to, humans, horses, dogs, cats, rabbits, rodents, swine, ovine, and primates, among others. Additionally, throughout the specification ranges of values are given along with lists of values for a particular parameter. In these instances, it should be noted that such disclosure includes not only the values listed, but also ranges of values that include whole and fractional values between any two of the listed values.

[0109] Embodiments of systems, devices and methods for delivering or eluting a treatment therapeutic (e.g., treatment fluid, treatment agent, powder, tablet, solid / liquid mixture, gel, drug, compound, composition) in the eye of a patient of various shapes and sizes are described herein. In the following description, numerous specific details are set forth to provide a thorough understanding of the embodiments; however, one skilled in the relevant art will recognize, based upon the disclosure herein, that the techniques described herein can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring certain aspects.

[0110] Reference throughout this description to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment, or example,PCT / US25 / 43600 26 August 2025 (26.08.2025) described herein. Thus, the appearances of the phrases “in one embodiment” or “in certain embodiments” in various places throughout this description are not necessarily all referring to the same embodiments or inventions. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Embodiments may mean an example or aspect or implementation and not necessarily a separate invention.

[0111] In several embodiments, a biocompatible drug delivery ocular implant is provided that comprises an outer shell that is shaped to define at least one interior lumen that houses a drug for release into an ocular space. The outer shell is polymeric in some embodiments, and in certain embodiments is substantially uniform in thickness, with the exception of areas of reduced thickness, through which the drug more readily passes from the interior lumen to the target tissue. In other words, a region of drug release may be created by virtue of the reduced thickness. In several other embodiments, the shell of the implant comprises one or more regions of increased drug permeability (e.g., based on the differential characteristics of portions of the shell such as materials, orifices, etc.), thereby creating defined regions from which the drug is preferentially released. In other embodiments, if the material of the outer shell is substantially permeable to a drug, the entire outer shell can be a region of drug release. In yet another embodiment, portions of the outer shell that surround where the drug is placed in the interior lumen or void of the device may be considered a region of drug release. For example, if the drug is loaded toward the distal end or in the distal portion of the device (e.g. the distal half or distal 2 / 3 of the device), the distal portion of the device will be a region of drug release as the drug will likely elute preferentially through those portions of the outer shell that are proximate to the drug. Therefore, as used herein, the term “region of drug release” shall be given its ordinary meaning and shall include the embodiments disclosed in this paragraph, including a region of drug permeability or increased drug permeability based on the characteristics of a material and / or the thickness of the material, one or more orifices or other passageways through the implant (also as described below), regions of the device proximate to the drug and / or any of these features in conjunction with one or more added layers of material that are used to control release of the drug from the implant. Regions of drug release may be at or near a proximal end of the implant, at or near a distal end of the implant, and / or along any portion of a main body of the implant. Depending on the context, these terms and phrases may be used interchangeably or explicitly throughout the present disclosure.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0112] In some embodiments, the implant body comprises a fluid flow pathway (e.g., with one or more inlets or inflow openings and one or more outlets or outflow openings). In some embodiments, the implant optionally comprises a retention feature. In some embodiments, the drug is encapsulated, coated, or otherwise covered with a biodegradable coating, such that the timing of initial release of the drug is controlled by the rate of biodegradation of the coating. In some embodiments, such implants are advantageous because they allow a variable amount of drug to be introduced (e.g., not constrained by dimensions of an implant shell) depending on the type and duration of therapy to be administered. In some embodiments having a shunt feature, the shunt feature works in conjunction with the drug to treat one or more symptoms of the disease or condition affecting the patient. For example, in some embodiments, the shunt removes fluid from the anterior chamber while the drug simultaneously reduces the production of ocular fluid. In other embodiments, as discussed herein, the shunt counteracts one or more side effects of administration of a particular drug (e.g., the shunt drains ocular fluid that was produced by the actions of the drug).

[0113] Following implantation at the desired site within the eye, drug is released from the implant in a targeted and controlled fashion, based on the design of the various aspects of the implant, preferably for an extended period of time. The implant and associated methods disclosed herein may be used in the treatment of pathologies requiring drug administration to the posterior chamber of the eye, the anterior chamber of the eye, or to specific tissues within the eye, such as the macula, the ciliary body, or other ocular target tissues.

[0114] Several embodiments of the systems and devices disclosed herein are particularly advantageous because they include one, several or all of the following benefits: (i) passively eluting a drug from an internal reservoir with minimal moving parts can reduce complications for a patient and reduce manufacturing costs; (ii) a simplified manufacturing process allows for an increase in manufacturing speed; (iii) compressing or deforming the eluting membrane, along with other factors that effect elution rate, can carefully limit and / or otherwise control an elution rate of a drug from the implant; (iv) a simplified retaining feature reduces complexify for retaining the implant components; (v) a selfflexing retaining feature that further reduces manufacturing steps for loading the implant with required components; (vi) a simplified design that improves delivery to target tissue; and / or (vii) a combination of body features (e.g., wall thickness(es), internal volume) andPCT / US25 / 43600 26 August 2025 (26.08.2025) proximal end features (e.g., retainer and membrane design) that facilitates generally zeroorder elution of therapeutics over a longer period of time.

[0115] Figure 1A is a cross-sectional view of an eye 100. Figure IB is an enlarged sectional view of the eye showing the relative anatomical locations of a trabecular meshwork 121, an anterior chamber 120, and Schlemm’s canal 122. With reference to Figures 1A and IB, the sclera 111 is a thick collagenous tissue that covers the entire eye 100 except a portion that is covered by a cornea 112. The cornea 112 is a thin transparent tissue that focuses and transmits light into the eye and through a pupil 114, which is a circular hole in the center of an iris 113 (colored portion of the eye). The cornea 112 merges into the sclera 111 at a juncture referred to as a limbus 115. A ciliary body 116 is vascular tissue that extends along the interior of the sclera 111 from the outer edges of the iris in the limbal region to a choroid 117. The ciliary body 116 is comprised of ciliary processes and ciliary muscle. Ciliary zonules extend from the ciliary processes to a lens 126. The choroid 117 is a vascular layer of the eye 100, located between the sclera 111 and a retina 118. An optic nerve 119 transmits visual information to the brain and is the anatomic structure that is progressively destroyed by glaucoma.

[0116] With continued reference to Figures 1A and IB, the anterior chamber 120 of the eye 100, which is bound anteriorly by the cornea 112 and posteriorly by the iris 113 and the lens 126, is filled with aqueous humor. Aqueous humor is produced primarily by the ciliary processes of the ciliary body 116 and flows into the posterior chamber, bounded posteriorly by the lens 126 and ciliary zonules and anteriorly by the iris 113. The aqueous humor then flows anteriorly through the pupil 114 and into the anterior chamber 120 until it reaches an anterior chamber angle 125, formed between the iris 113 and the cornea 112.

[0117] As best illustrated by the drawing of Figure IB, in a normal eye, at least some of the aqueous humor drains from the anterior chamber 120 through the trabecular meshwork 121 via the canalicular route. Aqueous humor passes through the trabecular meshwork 121 into Schlemm’s canal 122 and thereafter through a plurality of collector ducts and aqueous veins 123, which merge with blood-carrying veins, and into systemic venous circulation. Intraocular pressure is maintained by an intricate balance between secretion and outflow of aqueous humor in the manner described above. Glaucoma is, in most cases, characterized by an increased outflow resistance of aqueous humor from the anterior chamber 120, which leads to an increase in intraocular pressure. Fluids arePCT / US25 / 43600 26 August 2025 (26.08.2025) relatively incompressible, and thus intraocular pressure is distributed relatively uniformly throughout the eye 100.

[0118] As shown in Figure IB, the trabecular meshwork 121 lies adjacent a small portion of the sclera 111. Exterior to the sclera 111 is a conjunctiva 124. Traditional procedures that create a hole or opening for implanting a device through the tissues of the conjunctiva 124 and sclera 111 involve extensive surgery, as compared to surgery for implanting a device, such as described herein, which ultimately resides entirely within the confines of the sclera 111 and cornea 112.General

[0119] In some embodiments functioning as a drug delivery device alone, the implant is configured to deliver one or more drugs to anterior region of the eye in a controlled fashion while in other embodiments the implant is configured to deliver one or more drugs to the posterior region of the eye in a controlled fashion. In still other embodiments, the implant is configured to simultaneously deliver drugs (e.g., drugs described elsewhere herein) to both the anterior and posterior region of the eye in a controlled fashion (e.g., intraocular pressure-lowering drug that elutes over a longer duration of time, such as 1-3 years, and / or a steroid / antibiotic that elutes over a shorter duration of time, such as a few days). In yet other embodiments, the configuration of the implant is such that drug is released in a targeted fashion to a particular intraocular tissue, for example, the macula or the ciliary body. In certain embodiments, the implant delivers drug to the ciliary processes and / or the posterior chamber. In certain other embodiments, the implant delivers drug to one or more of the ciliary muscles and / or tendons (or the fibrous band). In some embodiments, implants deliver drug to one or more of Schl emm’s canal, the trabecular meshwork, the episcleral veins, the lens cortex, the lens epithelium, the lens capsule, the sclera, the scleral spur, the choroid, the suprachoroidal space, the supraciliary space, the subconjunctival space, retinal arteries and veins, the optic disc, the central retinal vein, the optic nerve, the macula, the fovea, and / or the retina. In still other embodiments, the delivery of drug from the implant is directed to an ocular chamber generally. It will be appreciated that each of the embodiments described herein may target one or more of these regions, and may also optionally be combined with a shunt or drainage feature.

[0120] In several embodiments, the implant comprises an outer shell or body. In some embodiments, the outer shell is tubular and / or elongate, while in other embodiments, other shapes (e.g., round, oval, cylindrical, etc.) are used. In certain embodiments, the outer shell is not biodegradable, while in others, the shell is optionallyPCT / US25 / 43600 26 August 2025 (26.08.2025) biodegradable. In several embodiments, the shell is formed to have at least a first interior lumen. In certain embodiments, the first interior lumen is positioned at or near the distal end of the device. In other embodiments, a lumen may run the entire length of the outer shell. In some embodiments, the lumen is subdivided. In certain embodiments, the first interior lumen is positioned at or near the proximal end of the device. In those embodiments additionally functioning as a shunt or drainage device, the shell may have one or more additional lumens and / or outlets within the portion of the device functioning as a shunt or drainage device.

[0121] In several embodiments, the drug (or drugs) is positioned within the interior lumen (or lumens) of the implant shell. In several embodiments, the drug is preferentially positioned within the more distal portion of the lumen. In some embodiments, the distal -most portion (e.g., distal-most 15 mm) of the implant lumen (or lumens) house the drug (or drugs) to be released. In some embodiments, the distal-most 1 - 10mm, including 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 mm, of the interior lumen(s) house the drug to be released. In several embodiments, the drug is preferentially positioned within the more proximal portion of the lumen.

[0122] In some embodiments, the drug diffuses through the shell or body and into the intraocular environment. In several embodiments, the outer shell material is permeable or semi-permeable to the drug (or drugs) positioned within the interior lumen, and therefore, at least some portion of the total elution of the drug occurs through the shell itself, in addition to that occurring through any regions of increased permeability, reduced thickness, orifices etc. In some embodiments, the drug diffuses through only a portion of the shell, and cannot diffuse through other portions of the shell. In some embodiments, the shell is not permeable but the implant includes a permeable lid or membrane through which the drug can elute at a predicted rate. The term “permeable” and related terms (e.g. “impermeable” or “semi permeable”) are used herein to refer to a material being permeable to some degree (or not permeable) to one or more drugs or therapeutic agents and / or ocular fluids. The term “impermeable” does not necessarily mean that there is no elution or transmission of a drug through a material, instead such elution or other transmission is negligible or very slight, e.g. less than about 3% of the total amount, including less than about 2% and less than about 1%.

[0123] In some embodiments, the implant is dimensioned such that, following implantation, the distal end of the implant is located sufficiently close to the macula that the drug delivered by the implant reaches the macula. In some embodiments incorporatingPCT / US25 / 43600 26 August 2025 (26.08.2025) a shunt feature, the implant is dimensioned such that when the distal end of the implant is positioned sufficiently near the macula, the proximal end of the implant extends into the anterior chamber of the eye. In those embodiments, outflow ports in the implant, described in more detail below, are positioned such that the aqueous humor will be drained into the uveoscleral outflow pathway or other physiological outflow pathway, such as Schl emm’s canal.

[0124] In some embodiments, the shunt feature works in conjunction with the drug delivery function to potentiate the therapeutic effects of the delivered agent. In other embodiments, the therapeutic effects of the delivered agent may be associated with unwanted side effects, such as fluid accumulation or swelling. In some embodiments, the shunt feature functions ameliorate the side effects of the delivered agent. It shall be appreciated that the dimensions and features of the implants disclosed herein may be tailored to attain targeted and / or controlled delivery to various regions of the eye while still allowing communication with a physiological outflow pathway.

[0125] For example, in some embodiments, the implant is dimensioned such that following implantation the distal end of the implant is located in the suprachoroidal space and the proximal end of the implant is located in the anterior chamber of the eye. In several embodiments, the drug eluted from the implant elutes or is otherwise released or delivered from the proximal end of the implant into the anterior chamber. In some embodiments incorporating a shunt feature, one or more outflow ports in the implant are positioned such that aqueous humor will drain into the uveoscleral pathway. In several embodiments, aqueous humor will drain from the anterior chamber to the suprachoroidal space or supraciliary space.

[0126] Delivery instruments may be used to facilitate delivery and / or implantation of the drug delivery implant to the desired location of the eye. The delivery instrument may be used to place the implant into a desired position, such as the inferior portion of the iris, the suprachoroidal space near the macula, in a position extending from the anterior chamber to Schlemm’s canal or to the suprachoroidal space, or other intraocular region, The design of the delivery instruments may take into account, for example, the angle of implantation and the location of the implant relative to an incision. For example, in some embodiments, the delivery instrument may have a fixed geometry, be shape-set, or actuated. In some embodiments, the delivery instrument may have adjunctive or ancillary functions, such as for example, injection of dye and / or viscoelastic fluid, dissection, or use as a guidewire. As used herein, the term “incision” shall be given its ordinary meaning andPCT / US25 / 43600 26 August 2025 (26.08.2025) may also refer to a cut, opening, slit, notch, puncture or the like. The incision may be a self-sealing incision.

[0127] In certain embodiments, the drug delivery implant may comprise or contain one or more drugs which may or may not be compounded with a bioerodible polymer or a bioerodible polymer and at least one additional agent. In still other embodiments, the drug delivery implant is used to sequentially deliver multiple drugs. Additionally, certain embodiments are constructed using different outer shell materials, and / or materials of varied permeability to generate a tailored drug elution profile. Certain embodiments are constructed using different numbers, dimensions and / or locations of orifices in the implant shell to generate a tailored drug elution profile. Certain embodiments are constructed using different polymer coatings and different coating locations on the implant to generate a tailored drug elution profile. Some embodiments elute drug at a constant rate, others yield a zero-order release profile. Yet other embodiments yield variable elution profiles. Still other embodiments are designed to stop elution completely or nearly completely for a predetermined period of time (e.g., a “drug holiday”) and later resume elution at the same or a different elution rate or elution concentration. Some such embodiments elute the same therapeutic agent before and after the drug holiday while other embodiments elute different therapeutic agents before and after the drug holiday.Drug Delivery Implants

[0128] The present disclosure relates to ophthalmic drug delivery implants which, following implantation at an implantation site, provide controlled release of one or more drugs to a desired target region within the eye, the controlled release being for an extended period of time. Depending on the embodiment, the implants may or may not elute or otherwise release a drug from the implant upon insertion. For example, implants according to certain embodiments disclosed herein do not elute or otherwise release or deliver a drug until a certain period of time has elapsed since implantation or until an external stimulus is applied to the implant in vivo. Implants according to certain embodiments disclosed herein can alternatively or in addition to above elute or otherwise release or deliver a drug to an ocular fluid within the eye upon being implanted at a target ocular tissue.

[0129] Figures 2A through 2E depict an implant embodiment employing materials with varied permeability to control the rate of drug release from the implant 210. The implant 210 can generally have a main body 211 portion comprising or consistingPCT / US25 / 43600 26 August 2025 (26.08.2025) essentially of a distal end 212 and a proximal end 214, a reservoir lid 228, and a cap 224 configured to retain or contain a treatment therapeutic (e.g., treatment fluid, drug, etc.) within the implant 210.

[0130] The distal end 212 of the implant 210 can comprise an implant connection end 216 configured to penetrate a tissue (e.g., a tissue within the eye). Further, the distal end of the implant 210, the proximal end of the implant 210, and / or any one or more portions or sections of a main body of the implant 210, may include one or more features (e.g. membranes, retainers, films, openings, pores) allowing treatment therapeutic release from within the reservoir 226 of the implant 210. The implant connection end 216 can have a sharpened end 218 with a material and design consistent with penetrating the ocular tissue at an implant location. In some embodiments, the implant connection end 216 can include a plurality of surfaces joined together to form sharp features to penetrate the ocular tissue. In some embodiments, the implant connection end 216 can include a conical shape to form a sharp tip to penetrate the ocular tissue. The implant connection end 216 can further comprise a retaining portion 219 or other feature designed to maintain the position of the implant 210 once implanted at the target ocular tissue.

[0131] In some embodiments, the implants have a generally sharpened forward, or distal, end and are self-trephinating (e.g., self-penetrating), so as to pass through tissue without pre-forming an incision, hole or aperture. The sharpened forward, or distal, end can be, for example, conical or tapered. A distal end of the implant can include a tissuepiercing end (e.g., tip). In some embodiments the tip is a conically shaped tip. In other embodiments, the tip can have a tapered angle . The tip can be sufficiently sharp to pierce eye tissue near the scleral spur of the eye, for example. The tip can also be sufficiently blunt so as not to substantially penetrate scleral tissue of the eye in some examples. In some embodiments, a conically shaped tip facilitates delivery of the shunt to the desired location. In embodiments comprising a shunting or aqueous humor drainage function, the distal end cap or tip may have one or more outlet openings to allow fluid flow (e.g., into Schlemm’s canal, a suprachoroidal or supraciliary space, or other physiological outflow pathway), such as shown, for example, in Figure 12. Each of the one or more outlet openings can communicate with at least one of the one or more lumens. The tip can be sufficiently sharp to pierce eye tissue. The tip also can be sufficiently blunt so as not to substantially penetrate eye tissue. The taper angle of the sharpened end can be, for example, about 20°±15° in some embodiments. The radius of the tip can be about 70 to about 200 microns. Where an outlet opening is formed at the distal end of the implant, the distalPCT / US25 / 43600 26 August 2025 (26.08.2025) portion can gradually increase in cross-sectional size in the proximal direction, preferably at a generally constant taper or radius or in a parabolic manner.

[0132] In some embodiments, the sharpened distal end 218 of the implant 210 can operate as a trocar to puncture or create an incision in the tissue. The sharpened distal end of the implant may be, for example, three-sided, four-sided, five-sided, or six-sided. Following advancement of the distal end of the implant, the tapered portion can be advanced through the puncture or incision. The tapered portion can operate to stretch or expand the tissue around the puncture or incision to accommodate the increasing size of the tapered portion as it is advanced through the tissue. The structural and / or functional features and aspects of the distal tips described in connection with Figures 2A-2D may be implemented with any of the examples illustrated in the other figures of the present application.

[0133] In some embodiments, the implant 210 can include a collet interface portion 222 designed to position the implant 210 within an implant applicator. In some embodiments, the collet interface portion 222 can include two wall members that circumscribe the implant 210 at a set distance apart, the distance being compatible an implant applicator. In some embodiments, the radial height of the walls forming the collet interface portion 222 can be of a height sufficient to prevent or substantially prevent premature disconnection of the implant 210 from the implant applicator. In some embodiments, the implant 210 does not comprise a collet interface portion 222.

[0134] In some embodiments, the reservoir lid 228 (e.g., drug release element, drug release membrane, reservoir membrane, porous membrane, drug membrane, etc.) can assist with retaining the treatment therapeutic (e.g., treatment fluid) within the reservoir 226 of the implant 210. In some embodiments, the reservoir lid 228 can be made of an impermeable material to prevent or substantially prevent the treatment therapeutic (e.g., treatment fluid) from prematurely exiting the implant 210. In some embodiments, portions of the reservoir lid 228 can be made of a permeable material to facilitate timed release of treatment therapeutic (e.g., treatment fluid) from the implant 210. In some embodiments, all or substantially all of the reservoir lid 228 can be made of a permeable material such that the drug can passively elute into the aqueous (e.g., ocular fluid, the fluid in the eye, etc.) to facilitate timed release of treatment therapeutic (e.g., treatment fluid) from the implant 210. In some embodiments, the reservoir lid 228 can be maintained against the proximal end 214 of the implant 210 by the cap 224.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0135] The release rate (e.g., flow rate, elution rate, etc.) of the drug (e.g., treatment therapeutic (e.g., treatment fluid)), treatment contents, medication, medicament, etc.) provided by or otherwise contained within the implant 210 can vary in part based on the characteristics of the reservoir lid 228. In some embodiments, the method of manufacturing the reservoir lid 228 affects the porosity, surface finish, and other characteristics relating to release rate of the drug through the reservoir lid 228. The release rate of the drug through the implant 210 is described further herein.

[0136] In some embodiments, the proximal end 214 can comprise or consist essentially of a ridge or other member to assist with connecting the cap 224 to the implant 210. In some embodiments, the cap 224 can be connected to the main body 211 by crimping, bending, or otherwise deforming a portion 225 of the cap 224 over the ridge or other member such that proximal movement of the cap 224 from the main body 211 is substantially prevented, as shown in Figure 2D. In some embodiments, the cap 224 can be connected to the implant 210 after the treatment therapeutic (e.g., treatment fluid) has been loaded into the reservoir 226 of the implant 210 by other methods. In some embodiments, the cap 224 can have a cap opening 229 in its proximal end to allow for treatment therapeutic (e.g., treatment fluid) to exit the implant 210. In some embodiments, the cap 224 can have a permeable membrane on its distal end to facilitate timed release of treatment therapeutic (e.g., treatment fluid) from the implant 210.

[0137] In some embodiments, treatment therapeutic (e.g., treatment fluid) can exit the implant 210 or elute to the eye by one or more of several treatment therapeutic (e.g., treatment fluid) pathways 220 that connect the reservoir 226 with the aqueous of the eye and / or the implant location. In some embodiments, the treatment therapeutic (e.g., treatment fluid) pathways 220 can be channels cut within the body of the implant 210.

[0138] In some embodiments, the treatment therapeutic (e.g., treatment fluid) pathway 220 can elute through the reservoir lid 228 and exit the implant 210 by an opening 229 in the cap 224.

[0139] In some embodiments, the treatment therapeutic (e.g., treatment fluid) pathway 220 can pass through a side wall in the main body 211 of the implant 210.

[0140] In some embodiments, the treatment therapeutic (e.g., treatment fluid) pathway 220 can pass through the distal end 212 of the implant 210 and exit the implant 210 in the implant connection end 216.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0141] In some embodiments, the reservoir 226 of the implant 210 can be multichambered to allow for different treatment therapeutics (e.g., treatment fluids) to flow to different portions of the eye.

[0142] The release rate of the treatment therapeutic (e.g., treatment fluid) from the reservoir 226 to the ocular fluid in the eye can depend on various factors, including but not limited to the following: the volume of the reservoir 226, the density of the reservoir lid 228, the geometry of the reservoir lid 228, the method of manufacture of the reservoir lid 228, the amount of compressive force exerted on the reservoir lid 228 by the cap 224, the size of the cap opening 229, and / or the composition of the drug provided by the implant 210.

[0143] In several embodiments, the treatment therapeutic has a release rate of 25 ng / day to 250 ng / day: (e.g., 25 ng / day to 50 ng / day, 50 ng / day to 75 ng / day, 75 ng / day to 100 ng / day, 100 ng / day to 125 ng / day, 125 ng / day to 150 ng / day, 150 ng / day to 175 ng / day, 175 ng / day to 200 ng / day, 200 ng / day to 225 ng / day, 225 ng / day to 250 ng / day, overlapping ranges thereof or any release rate within the recited ranges). In several embodiments, the treatment therapeutic has a release rate greater than 250 ng / day.

[0144] In several embodiments, the reservoir has a volume of InL to 500 nL (e.g., 1 nL to 10 nL, 10 nL to 100 nL, 50 nL to 150 nL, 150 nL to 250 nL, 250 nL to 500 nL, overlapping ranges thereof or any volume within the recited ranges). In some embodiments, the reservoir has a volume of at least 100 nL. In some embodiments, the reservoir has a volume of at least 120 nL. In some embodiments, the reservoir has a volume of at least 150 nL. In some embodiments, the reservoir has a volume of at least 200 nL. In several embodiments, the reservoir has a volume greater than 500 nL. In some embodiments, the reservoir is filled with a drug having a drug volume within 10% of the reservoir volume. In some embodiments, the reservoir is filled with a drug volume having a volume within 5% of the reservoir volume. In some embodiments, the reservoir is filled with a drug having a drug volume substantially equal to the reservoir volume.

[0145] Figures 3A through 3G depict various embodiments of an implant and various components, configured for substantially similar use of other implants as disclosed herein. Figure 3A depicts an implant 310 that can have structural and / or functional features substantially similar to other implants disclosed herein. In some embodiments, the implant 310 can generally have a main body 311 portion comprising a distal end 312 and a proximal end 314, a membrane 328, and a retainer 324 configured to retain or contain a treatment therapeutic (e.g., treatment fluid, liquid, drug, powder, tablet, sohd / liquid mixture,PCT / US25 / 43600 26 August 2025 (26.08.2025) compound, composition, gel) within the implant 310. In some embodiments, the main body 311 portion is formed as a unitary component, and the proximal end 314 of the main body 311 portion defines the proximal end of the implant 310. The implant 310 can have an implant connection end 316, a sharpened end 318, and a retaining portion 320 that function substantially similarly to the implant connection end 216, sharpened end 218, and retaining portion 219 as described herein.

[0146] In some embodiments, the implant 310 can include an interface feature 322 (e.g. groove, divot, bend, recess, protrusion, ridge, applicator interface, collet portion, collet interface portion, interfacing feature etc.) designed to position the implant 310 within an implant applicator or implant deliver}' instrument (e.g., to be grasped or carried by or otherwise interface with a portion of an implant applicator or implant delivery instrument). In some embodiments, the interface feature 322 can be a divot formed in the main body 311 of the implant 310. The divot can reduce the profile of the main body 311 such that an engagement or interface portion of an implant applicator or delivery instrument can circumscribe or partially surround a portion of the implant 310. The interface feature 322 can include an angled recess such that the implant 310 can self-align with the engagement or interface portion of the implant applicator as the implant applicator connects with the implant 310. In some embodiments, the depth and angle of the interface feature 322 can be of size and shape sufficient to prevent or substantially prevent premature disconnection of the implant 310 from the implant applicator. In some embodiments, the implant 310 does not include an interface feature 322.

[0147] In some embodiments, such as shown in Figures 9A and 9B, the implant 310 (labeled as 910 in Figures 9A and 9B) does not include an interface feature. In such embodiments, the implant 310, 910 has a substantially smooth wall and engages with an implant applicator by frictional forces. Such a design may allow for simplified manufacturing and design of the implant and implant applicator.

[0148] In some embodiments, such as shown in Figures 10A and 10B, the implant 310 ((labeled as 1010 in Figures 10A and 10B) has a main body that has a thicker wall at the proximal region than the distal region. A thicker proximal main body wall may provide structural support for a sealing structure (e.g., spacers 329 and retainer 324). In such embodiments, the main body 311 may have an outer diameter at the proximal end that is greater than at the distal end.

[0149] In some embodiments, the reservoir 326 of the implant 310 can be loaded with a treatment therapeutic (e.g., drug, fluid, medicine, medicament, drugPCT / US25 / 43600 26 August 2025 (26.08.2025) treatment, treatment drug, etc.). In some embodiments, the treatment therapeutic (e.g., fluid) can elute through a permeable membrane 328 (e.g., drug release element, drug release membrane, reservoir lid, reservoir membrane, porous membrane, drug membrane, etc.) of the implant 310 to distribute the treatment therapeutic (e.g., fluid) at a predetermined rate. In some embodiments, the main body 311 or portions of the main body 311 may be selectively permeable to allow treatment therapeutic (e.g., fluid) to exit the reservoir 326 via the main body 311. The membrane 328 can passively elute the drug into the aqueous (e.g., ocular fluid, the fluid in the eye, etc.) once the implant 310 is implanted at the target ocular tissue.

[0150] In some embodiments, once the treatment therapeutic (e.g., fluid) is loaded into the reservoir 326, the proximal end 314 of the implant 310 can be fitted with one or more spacers 329, a permeable membrane 328, and a retainer 324. In some embodiments, the order or quantity of components inserted into the implant 310 can be modified as desired or required. Figure 3B displays an exploded view of the components in the order they can be arranged within the proximal end 314 of the implant 310, according to one embodiment. Figure 3C depicts a cross-sectional view of the implant 310 to show the arrangement of the interior components once installed in the implant 310, according to one embodiment.

[0151] In some embodiments, the membrane 328 can be configured to passively elute the treatment therapeutic (e.g., treatment fluid) stored within the reservoir 326 at a predetermined rate, as desired or required. The membrane 328 can be manufactured by extrusion, molding, or by other methods as desired or required to achieve the desired elution rate. In some embodiments, the thickness, porosity, and consistency of the membrane 328 can be modified or controlled during the manufacturing process. In some embodiments, the surface finish of the eluting sides of the membrane 328 can be modified or controlled during the manufacturing process.

[0152] The release rate of the drug provided by the implant 310 can vary in part based on the characteristics of the membrane 328. In some embodiments, the method of manufacturing the membrane 328 affects the porosity, surface finish, and other characteristics relating to release rate of the drug through the membrane 328.

[0153] The release rate of the treatment therapeutic (e.g., treatment fluid) from the reservoir 326 to the ocular fluid in the eye can depend on various factors, including but not limited to the following: the volume of the reservoir 326, the density of the membrane 328, the geometry of the membrane 328, the method of manufacture of the membrane 328,PCT / US25 / 43600 26 August 2025 (26.08.2025) the amount of compressive force exerted on the membrane 328 by the retaining element (either the retainer 324 or the spring retainer 440, as described herein), the size of the openings in the retaining element, and / or the composition of the drug provided by the implant 210.

[0154] In some embodiments, the membrane 328 can be configured to prevent or substantially prevent entry into the reservoir 326 of aqueous fluids or other fluids, as desired or required.

[0155] In some embodiments, the membrane 328 can be configured to be compressed, deformed, or otherwise manipulated during installation. Deformation of the membrane 328 can assist in controlling the release rate of the drug from the implant 310. In some embodiments, the membrane 328 may not be compressed within the implant 310.

[0156] In some embodiments, the membrane 328 can comprise an ethylene vinyl acetate terpolymer (EVA), polypropylene, polyimide, glass, nitinol, polyvinyl alcohol, polyvinyl pyrolidone, collagen, chemically-treated collagen, polyethersulfone (PES), poly(styrene-isobutyl-styrene), polyurethane, ethyl vinyl acetate (EVA), polyetherether ketone (PEEK), Kynar (Polyvinylidene Fluoride; PVDF), Polytetrafluoroethylene (PTFE), Polymethylmethacrylate (PMMA), Pebax, acrylic, polyolefin, polydimethylsiloxane and other silicone elastomers, polypropylene, hydroxyapetite, titanium, gold, silver, platinum, other metals and alloys, ceramics, plastics and mixtures or combinations thereof, or other suitable biocompatible permeable materials. In some embodiments, the deformation of the membrane 328 during assembly may affect the permeability of one or more portions of the membrane 328.

[0157] In some embodiments, deformation of the membrane 328 (e.g., at a surface in contact with one or more spacers 329) may prevent or substantially prevent elution of treatment therapeutic (e.g., treatment fluid) in one or more portions of the membrane 328. In some embodiments, elution of treatment therapeutic (e.g., treatment fluid) through a compressed portion 328A (e.g., sealed portion, deformed portion, compacted portion, deformed region, deformed zone, etc.) of the membrane 328 compressed or deformed by the one or more spacers 329 (e.g., positioning elements, compressing elements, membrane aligners, membrane compressors, etc.) may be substantially or entirely prevented. In some embodiments, the compressed portion 328A of the membrane 328 may prevent elution of treatment therapeutic (e.g., treatment fluid) from the reservoir 326 between the membrane 328 and the main body 311 of the implant 310. In some embodiments, the compressed portion 328A can form a seal along sealingPCT / US25 / 43600 26 August 2025 (26.08.2025) surface 332 where it contacts portions of the implant 310, including but not limited to the main body 311, the proximal end 314, and any spacer 329 the compressed portion 328 A contacts. Along these sealing surfaces 332, elution of the contents of the implant 310 may be prevented or substantially prevented. In some embodiments, the uncompressed portion 328B (i.e., the portion or portions of the membrane 328 that are not compressed by one or more spacers 329) may deform or expand around openings in the spacer 329. In some embodiments, the uncompressed portion 328B may elute fluid at an expected rate. The opening in the spacers 329, the original thickness of the membrane 328, and the thickness of the spacers 329 can affect the elution rate of the treatment therapeutic (e.g., treatment fluid) from the implant 310. The uncompressed portion 328B or portions of the membrane 328 that are not in contact with the one or more spacers 329 may also bulge, expand, or deform but may not be mechanically compressed or deformed by the one or more spacers or other elements themselves.

[0158] In some embodiments, the membrane 328 can be compressed to be a certain percentage of its original thickness. In some embodiments, the membrane 328 can be compressed approximately 40%. In some embodiments, the membrane 328 can be compressed less than 40% (e.g., 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, less than 30%, 0%, and any intervening values). In some embodiments, the membrane 328 can be compressed more than 40% (e.g., 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, more than 50%, 99%, almost 100%, and any intervening values). In some embodiments, strain along the course of the membrane 328 can vary due to the compressive forces exerted onto the membrane 328 by, for example, contacting portions of any spacer 329, proximal end 314, or implant 310. In some embodiments, the maximum stress within a membrane 328 is more than 4.5 megapascal (MPa). In some embodiments, the maximum stress within a membrane 328 is less than 5 megapascal (MPa).

[0159] In some embodiments, the membrane 328 can be compressed with a certain compressive force by, for example, contacting portions of any spacer 329, proximal end 314, or implant 310. In some embodiments, the membrane 328 can be compressed along the proximal-distal axis to be deformed by a certain thickness in a compressed portion 328 A. In some embodiments, the membrane 328 can be deformed by 50 microns (50 pm). In some embodiments, the membrane 328 can be deformed by less than 50 microns (e.g., 49 pm, 48 pm, 47 pm, 46 pm, 45 pm, 44 pm, 43 pm, 42 pm, 41 pm, 40 pm, less than 40 pm, and any intervening values). In some embodiments, the membrane 328 can bePCT / US25 / 43600 26 August 2025 (26.08.2025) deformed by more than 50 microns (e.g., 51 m, 52 pm, 53 pm, 54 pm, 55 pm, 56 pm, 57 pm, 58 pm, 59 pm, 60 pm, more than 60 pm, and any intervening values).

[0160] In some embodiments, the membrane 328 can expand radially outward from the proximal-distal axis when compressed within an implant 310. In some embodiments, the membrane 328 can have an original radius of 125 pm. In some embodiments, the membrane 328 can have an original radius more than 125 pm. In some embodiments, the membrane 328 can have an original radius less than 125 pm. In some embodiments, the membrane 328 can expand by approximately 70% radially outward when compressed or otherwise deformed in the proximal-distal direction. In some embodiments, the membrane 328 can expand by more than 70% (e.g., 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, more than 80%, and any intervening values). In some embodiments, the membrane 328 can expand by less than 70% (e.g., 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61%, 60%, less than 60%, and any intervening values). In some embodiments, the membrane 328 can expand radially upon longitudinal compression to conform to the internal radial dimensions of the main body 311.

[0161] In some embodiments, the force required to compress the membrane 328 can be minimized to reduce strain imposed on components of the implant 310. In some embodiments, the force required to compress the membrane 328 can be approximately 0.2 pound-force (Ibf). In some embodiments, the force required to compress the membrane 328 is less than 0.2 pound-force (0.19 Ibf, 0.18 Ibf, 0.17 Ibf, 0.16 Ibf, 0.15 Ibf, 0.14 Ibf, 0.13 Ibf, 0.12 Ibf, 0.11 Ibf, 0.10 Ibf, less than 0.10 Ibf, and any intervening values). In some embodiments, the force required to compress the membrane 328 is more than 0.2 poundforce (0.21 Ibf, 0.22 Ibf, 0.23 Ibf, 0.24 Ibf, 0.25 Ibf, 0.26 Ibf, 0.27 Ibf, 0.28 Ibf, 0.29 Ibf, 0.30 Ibf, more than 0.30 Ibf, and any intervening values).

[0162] In some embodiments, the membrane 328 can be compressed along the proximal-distal axis to be deformed by a certain thickness in a compressed portion. In some embodiments, the membrane 828 can be deformed by 50 microns (50 pm). In some embodiments, the membrane 828 can be deformed by less than 50 microns (e.g., 49 pm, 48 pm, 47 pm, 46 pm, 45 pm, 44 pm, 43 pm, 42 pm, 41 pm, 40 pm, less than 40 pm, and any intervening values). In some embodiments, the membrane 1028 can be deformed by more than 50 microns (e.g., 51 pm, 52 pm, 53 pm, 54 pm, 55 pm, 56 pm, 57 pm, 58 pm, 59 pm, 60 pm, more than 60 pm, and any intervening values). In some embodiments, the membrane 328 is configured to be deformed by between 35 and 75 pm (e.g., 35 to 50 pm,PCT / US25 / 43600 26 August 2025 (26.08.2025)45 to 55 pm, 40 to 60 pm, 50 to 75 pm, overlapping ranges, or any value within the recited ranges).

[0163] In some embodiments, one or more spacers 329 (e.g., washers, seals, etc.) may be used to position the membrane 328 or modify its elution rate. In some embodiments, the one or more spacers 329 can be of the same material as main body 311 of the implant 310. In some embodiments, the one or more spacers 329 may deform a portion of the membrane 328 to form a compressed portion 328A (as shown in Figure 3D, described herein). In some embodiments, the sealing surfaces 332 formed at the points the compressed portion 328A of the membrane 328 contacts other components of the implant 310 can prevent or substantially prevent elution through those sealing surfaces 332. Therefore, in some embodiments, the sealing surfaces 332 of the membrane 328 can direct the elution of a treatment therapeutic (e.g., treatment fluid) through the uncompressed portion 328B of the membrane 328, out the proximal end 314 of the implant 310. In some embodiments, even if the entire membrane is deformed, the area(s) in compression may lead to material flow into the uncompressed areas, which cause the uncompressed areas to become larger and more variable or permeable.

[0164] In some embodiments, the spacer 329 or retainer 324 can reduce or mitigate at least some of the stress or strain exerted on the membrane 328 during compression. In some embodiments, the retainer 324 can reduce stress exerted on the membrane 328 that results from the use of the implant 310. In some embodiments, these stresses can result from compression of the membrane 328, expansion of one or more components of the implant 310 (such as the treatment therapeutic (e.g., treatment fluid) within the reservoir 326), formation of a vacuum within the implant 310 as the treatment therapeutic (e.g., treatment fluid) exits the implant 310, and any other factors. In some embodiments, the retainer 324 can include a central portion to prevent or substantially prevent severe deformation of a membrane 328 during use of the implant 310.

[0165] In some embodiments, a portion of the main body 311 of the implant 310 can function as the spacer such that no sealing member may be needed between the membrane 328 and the main body 311. In some embodiments, the spacer 329 can be integrally formed or combined with the retainer 324 to form a retainer spacer 330 such that no sealing member may be needed between the membrane 328 and the retainer 324. In some embodiments, the spacers can be integrally formed or incorporated into both the main body and the retainer 324 such that no spacer 329 is needed. Figures 3E and 3F demonstrate example configurations of such embodiments. The embodiment of the retainerPCT / US25 / 43600 26 August 2025 (26.08.2025) spacer 330 depicted in Figure 3F can specifically deform during insertion into the proximal end 314 of the implant 310. The retainer spacer 330 can return to an uncompressed state (e.g., undeformed state, rest state, original state, etc.) after being fully inserted and be prevented from moving proximally by contacting an interface portion 334 on the proximal end 314 of the implant 310. In some embodiments, the retainer spacer 330 does not require the proximal end 314 of the implant 310 to be crimped, bent, or otherwise deformed to prevent or substantially prevent proximal movement of the components of the implant 310 from the main body 311.

[0166] In some embodiments, the spacer 329 can be combined with the retainer 324 to form a retainer spacer 330. The retainer spacer 330 can be configured to deform or expand to accommodate its insertion into a proximal end 314 of an implant 310. In some embodiments, the retainer spacer 330 can resist proximal movement relative to the main body 311 similar to other retainers 324 as disclosed herein. In some embodiments, the retainer spacer 330 can be made of one or more of multiple materials, such as, for example, one or more of polypropylene, polyimide, glass, polyvinyl alcohol, polyethersulfone (PES), poly(styrene-isobutyl-styrene), polyurethane, polyetherether ketone (PEEK), Polytetrafluoroethylene (PTFE), Polymethylmethacrylate (PMMA), acrylic, polyolefin, polydimethylsiloxane and other silicone elastomers, polypropylene, titanium, gold, other metals and alloys, ceramics, plastics and mixtures or combinations thereof. In embodiments in which multiple different materials are used, one portion of the retainer spacer 330 may have a different durometer or ductility compared to another portion of the retainer spacer 330.

[0167] In some embodiments, the retainer 324 can be configured to interface with a portion of the main body 311 of the implant 310 to substantially prevent proximal movement of the components of the implant 310 once the retainer 324 is installed. Once the reservoir 326 has been filled with the desired quantity of treatment therapeutic (e.g., treatment fluid) and the membrane 328 and one or more spacers 329 have been positioned (if a particular embodiment requires any spacers 329), the retainer 324 can be installed in the implant 310 to substantially prevent proximal movement of the components of the implant 310.

[0168] In some embodiments, the proximal end 314 can be configured such that, after all components (e.g., the main body 311, the membrane 328, one or more spacers 329 if required, the retainer 324, etc.) of the implant 310 have been assembled, the retainer 324 can be inserted into the proximal end 314 of the main body 311. In some embodiments,PCT / US25 / 43600 26 August 2025 (26.08.2025) the proximal most surface of the retainer 324 may be more distal than the distal-most surface of the relief 313, in which case no compression is required. If, however, the proximal-most surface of the retainer 324 is not more distal than the distal-most surface of the relief 313, the internal components of the implant 310 may be compressed until the proximal-most surface of the retainer 324 is more distal than the distal-most surface of the relief 313. In some embodiments, the retainer 324 may not be necessary, and the components inserted into the proximal end 314 (e.g., the membrane 328, one or more spacers 329, etc.) can be compressed or deformed, if required, such that the proximal-most surface of a spacer 329 proximal the membrane 328 is more distal than the distal-most surface of the relief 313.

[0169] Once appropriately positioned, the one or more reliefs 313 in the proximal end 314 of the main body 311 may be crimped, bent, or otherw ise deformed to prevent or substantially prevent proximal movement of the components of the implant 310 from the mam body 311. The crimped portions 315 of the implant 310 can impede proximal movement of the retainer 324 or, in some embodiments, a spacer 329 proximal the membrane 328, and thus the other internal components, by contacting the proximal most surface of the retainer 324 or spacer 329 w ith the distal most surface of the relief 313. In some embodiments, this crimping portion 315 can be along a proximal end 314 of the implant 310 proximal to the reliefs 313 cut in the main body 311.

[0170] In some embodiments, two reliefs 313 are cut into the proximal end 314. In some embodiments, one, three, four, or more than four reliefs 313 can be cut into the proximal end 314. The reliefs 313 can assist in carefully deforming the proximal end 314 of the implant 310 around the retainer 324 once the implant 310 is filled with the treatment therapeutic (e.g., treatment fluid) and the various components are arranged. In some embodiments, the reliefs 313 are cut completely through the proximal end 314 of the main body 311. In some embodiments, the reliefs 313 are partial cuts into the surface of the proximal end 314, to facilitate bending of the components along a score line.

[0171] Figure 3G depicts an isometric perspective view of an embodiment of an implant 310 with portions 315 of its proximal end 314 crimped around a retainer 324. In some embodiments, more or less reliefs 313, and accordingly more or less crimping portions 315, can be utilized to limit the proximal movement of the retainer 324 relative to the main body 311. The number of reliefs 313 and crimped portions 315 can vary as desired or required. In the embodiment depicted in Figure 3G, two reliefs 313, and thus two crimped portions 315, are depicted.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0172] In some embodiments, the retainer 324 can have one or more openings 325 configured to allow the treatment therapeutic (e.g., treatment fluid) to passively elute from the permeable membrane 328 to the ocular fluid in the eye. In some embodiments, one or more openings 325 can be present in the retainer 324. In some embodiments, more or less openings 325 can be present in the retainer 324. In some embodiments, the size of the openings 325 can be changed. The size and quantity of openings 325 in the retainer 324 can affect the rate of treatment therapeutic (e.g., treatment fluid) elution in an implant 310. In some embodiments, it is beneficial to minimize the area of the openings 325 to limit the elution rate of the treatment therapeutic (e.g., treatment fluid) from the implant 310. In some embodiments, the openings 325 have a cross-section area of about 0 to 10 pm2. In some embodiments, the openings 325 have cross-section area of about 10 to 50 pm2. In some embodiments, the openings 325 have a cross-section area of about 50 to 100 pm2. In some embodiments, the openings 325 have a cross-section area of about 100 to 150 pm2. In some embodiments, the openings 325 have a cross-section area of about 150 to 200 pm2. In some embodiments, the openings 325 have a cross-section area of about 200 to 250 pm2. In some embodiments, the openings 325 have a cross-section area of about 250 to 300 pm2. In some embodiments, the openings 325 have a cross-section area of about 300 to 350 pm2. In some embodiments, the openings 325 have a cross-section area of about 350 to 400 pm2. In some embodiments, the openings 325 have a cross-section area of greater than 400 pm2. In some embodiments, the openings 325 have a cross-section area between 10 - 400 pm2(e.g., 10 to 100 pm2, 50 to 200 pm2, 100 to 300 pm2, 150 to 350 pm2, 200 to 400 pm2, overlapping ranges thereof, or any value within the recited ranges).

[0173] Figures 4A through 4E depict an alternative embodiment or example of an implant, configured for substantially similar use as other implants disclosed herein. Figure 4A depicts an implant 410 that can have structural and / or functional features substantially similar to other implants disclosed herein (e.g., implants 310, 510, 610, 710, 810, 910, 1010). For example, elements labeled with similar numbering as in Figures 3A- 3G but with a leading “4” may include similar structural and / or functional features even if not specifically described in connection with Figures 4A - 4E. In some embodiments, the implant 410 can generally have a main body 411 portion comprising or consisting essentially of a distal end 412 and a proximal end 414, a membrane 428, and a spring retainer 440 configured to retain or contain a treatment therapeutic (e.g., treatment fluid) within the implant 410. The implant 410 can have an implant connection end 416, a sharpened end 418, and a retaining portion 420 that function substantially similarly to thePCT / US25 / 43600 26 August 2025 (26.08.2025) implant connection end 216, sharpened end 218, and retaining portion 219 as described herein.

[0174] In some embodiments, the implant 410 can include an interface feature 422 (e.g. groove, divot, bend, recess, protrusion, ridge, applicator interface, collet portion, collet interface portion, interfacing feature etc.) designed to position the implant 410 within an implant applicator or implant delivery instrument. In some embodiments, the interface feature 422 can be a divot formed in the main body 411 of the implant 410. The divot can reduce the profile of the main body 411 such that an engagement or interface portion of an implant applicator can circumscribe or partially surround a portion of the implant 410. The interface feature 422 can include an angled recess such that the implant 410 can self-align with the engagement or interface portion of the implant applicator as the implant applicator connects with the implant 410. In some embodiments, the depth and angle of the interface feature 422 can be of a size and shape sufficient to prevent or substantially prevent premature disconnection of the implant 410 from the implant applicator.

[0175] In some embodiments, the reservoir 426 of the implant 410 can be loaded with a treatment therapeutic (e.g., drug, medicine, medicament, drug treatment, treatment drug, etc.). In some embodiments, the treatment therapeutic (e.g., treatment fluid) can passively elute through a permeable membrane 428 of the implant 410 to distribute the treatment therapeutic (e.g., treatment fluid) at a predetermined rate. In some embodiments, the main body 411 or portions of the main body 411 may be selectively permeable to allow treatment therapeutic (e.g., treatment fluid) to exit the reservoir 426 via the main body 411.

[0176] In some embodiments, once the treatment therapeutic (e.g., treatment fluid) is loaded into the reservoir 426, the proximal end 414 of the implant 410 can be fitted with one or more spacers 429, a permeable membrane 428, and a retainer 424. In some embodiments, the order or quantity of components inserted into the implant 410 can be modified as desired or required. Figure 4B displays an exploded view of the components in the order they can be arranged within the proximal end 414 of the implant 410, according to one embodiment of assembly or manufacture. Figure 4C depicts a cross-sectional view of the implant 410 to show the arrangement of the interior components once installed or assembled in the implant 410, according to one embodiment.

[0177] In some embodiments, the membrane 428 can be configured to passively elute the treatment therapeutic (e.g., treatment fluid) stored within the reservoir 426 at a predetermined rate, as desired or required. The membrane 428 can be manufactured by extrusion, molding, or by other methods as desired or required to achieve the desired elutionPCT / US25 / 43600 26 August 2025 (26.08.2025) rate. In some embodiments, the thickness, porosity, and consistency of the membrane 428 can be modified or controlled during the manufacturing process. In some embodiments, the surface finish of the eluting sides of the membrane 428 can be modified or controlled during the manufacturing process.

[0178] The release rate of the drug provided by the implant 410 can vary in part based on the characteristics of the membrane 428. In some embodiments, the method of manufacturing the membrane 428 affects the porosity, surface finish, and other characteristics relating to release rate of the drug through the membrane 428.

[0179] The release rate of the treatment therapeutic (e.g., treatment fluid) from the reservoir 426 to the ocular fluid in the eye can depend on various factors, including but not limited to the following: the volume of the reservoir 426, the density of the membrane 428, the geometry of the membrane 428, the method of manufacture of the membrane 428, the amount of compressive force exerted on the membrane 428 by the retaining element (either the retainer 424 or the spring retainer 440, as described herein), the size of the openings in the retaining element, the size(s) of the opening(s) in the spacer(s) 329, and / or the composition of the drug provided by the implant 410. In some embodiments, an area of an opening of a spacer 329 is less than a combined area of openings of the retaining element. The volume of the reservoir 426 may have the same ranges of volume described above in connection with prior figures.

[0180] In some embodiments, the membrane 428 can be configured to prevent or substantially prevent entry into the reservoir 426 of aqueous fluids or other fluids, as desired or required.

[0181] In some embodiments, the membrane 428 can be configured to be compressed (e.g., deformed, manipulated, constrained, etc.) during installation or manufacture. Compression or deformation of the membrane 428 can assist in controlling the release rate of the drug from the implant 410. In some embodiments, the membrane 428 may not be compressed or deformed within the implant 410.

[0182] In some embodiments, the membrane 428 can comprise an ethylene vinyl acetate terpolymer (EVA), or other suitable biocompatible permeable materials. In some embodiments, the compression or deformation of the membrane 428 during assembly may affect the permeability of one or more portions of the membrane 428.

[0183] In some embodiments, compression or deformation of the membrane 428 may prevent or substantially prevent elution of treatment therapeutic (e.g., treatment fluid) in one or more portions of the membrane 428, similarly to how membrane 328 ofPCT / US25 / 43600 26 August 2025 (26.08.2025)Figures 3A-3G has been described to be compressed, deformed, or otherwise manipulated herein. In some embodiments, elution of treatment therapeutic (e.g., treatment fluid) through a compressed portion of the membrane 428 compressed by the one or more spacers 429 (e.g., positioning elements, compressing elements, membrane aligners, membrane compressors, etc.) may be substantially or entirely prevented. In some embodiments, the compressed or deformed portion of the membrane 428 may prevent elution of treatment therapeutic (e.g., treatment fluid) from the reservoir 426 between the membrane 428 and the main body 411 of the implant 410. In some embodiments, the uncompressed portion (e.g., natural portion, original portion, resting portion, undeformed portion, etc.) may deform or expand around openings in the spacer 429. In some embodiments, the uncompressed portion may elute fluid at an expected rate. The opening in the spacers 429, the original thickness of the membrane 428, and the thickness of the spacers 429 can affect the elution rate of the treatment therapeutic (e.g., treatment fluid) from the implant 410. In some embodiments, the openings in the spacer 429 have cross-section area of about 0 to 10 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of about 10 to 50 pm2. In some embodiments, the openings in the spacer 429 have a crosssection area of about 50 to 100 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of about 100 to 150 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of about 150 to 200 pm2. In some embodiments, the openings in the spacer 429 have cross-section area of about 200 to 250 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of about 250 to 300 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of about 300 to 350 pm2. In some embodiments, the openings in the spacer 329 have a crosssection area of about 350 to 400 pm2. In some embodiments, the openings in the spacer 429 have a cross-section area of greater than 400 pm2. In some embodiments, the openings in the spacer 329 have a cross-section area of between 10 and 400 pm2(e.g., between 10 and 100 pm2, between 50 and 150 pm2, between 100 and 250 pm2, between 150 and 300 pm2, between 200 and 400 pm2, betw een 100 and 400 pm2, overlapping ranges thereof, or any value within the recited ranges).

[0184] In some embodiments, the membrane 428 can be compressed to be a certain percentage of its original thickness. In some embodiments, the membrane 428 can be compressed approximately 40%. In some embodiments, the membrane 428 can be compressed less than 40% (e.g., 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, less than 30%, 0%, and any intervening values). In some embodiments, the membrane 428PCT / US25 / 43600 26 August 2025 (26.08.2025) can be compressed more than 40% (e.g., 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, more than 50%, 99%, almost 100%, and any intervening values). In some embodiments, strain along the course of the membrane 428 can vary due to the compressive forces exerted onto the membrane 428 by, for example, contacting portions of any spring retainer 440, proximal end 414, or implant 410. In some embodiments, the maximum stress within a membrane 428 is more than 4.5 megapascal (MPa). In some embodiments, the maximum stress within a membrane 428 is less than 5 megapascal (MPa).

[0185] In some embodiments, the membrane 428 can be compressed with a certain compressive force by, for example, contacting portions of any spring retainer 440, proximal end 414, or implant 410. In some embodiments, the membrane 428 can be compressed along the proximal -distal axis to be deformed by a certain thickness in a compressed portion. In some embodiments, the membrane 428 can be deformed by 50 microns (50 pm). In some embodiments, the membrane 428 can be deformed by less than 50 microns (e.g., 49 pm, 48 pm, 47 pm, 46 pm, 45 pm, 44 pm, 43 pm, 42 pm, 41 pm, 40 pm, less than 40 pm, and any intervening values). In some embodiments, the membrane 428 can be deformed by more than 50 microns (e.g., 51 pm, 52 pm, 53 pm, 54 pm, 55 pm, 56 pm, 57 pm, 58 pm, 59 pm, 60 pm, more than 60 pm, and any intervening values).

[0186] In some embodiments, the membrane 428 can expand radially outward from the proximal-distal axis when compressed within an implant 410. In some embodiments, the membrane 428 can have an original radius of 125 pm. In some embodiments, the membrane 428 can have an original radius more than 125 pm. In some embodiments, the membrane 428 can have an original radius less than 125 pm. In some embodiments, the membrane 428 can expand by approximately 70% radially outward when compressed or otherwise deformed in the proximal-distal direction. In some embodiments, the membrane 428 can expand by more than 70% (e.g., 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, more than 80%, and any intervening values). In some embodiments, the membrane 428 can expand by less than 70% (e.g., 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61%, 60%, less than 60%, and any intervening values).

[0187] In some embodiments, the force required to compress the membrane 428 can be minimized to reduce strain imposed on components of the implant 410. In some embodiments, the force required to compress the membrane 428 can be approximately 0.2 pound-force (Ibf). In some embodiments, the force required to compress the membrane 428 is less than 0.2 pound-force (0.19 Ibf, 0.18 Ibf, 0.17 Ibf, 0.16 Ibf, 0.15 Ibf, 0.14 Ibf, 0.13 Ibf, 0.12 Ibf, 0.11 Ibf, 0.10 Ibf, less than 0.10 Ibf, and any intervening values). In somePCT / US25 / 43600 26 August 2025 (26.08.2025) embodiments, the force required to compress the membrane 428 is more than 0.2 poundforce (0.21 Ibf, 0.22 Ibf, 0.23 Ibf, 0.24 Ibf, 0.25 Ibf, 0.26 Ibf, 0.27 Ibf, 0.28 Ibf, 0.29 Ibf, 0.30 Ibf, more than 0.30 Ibf, and any intervening values).

[0188] In some embodiments, one or more spacers 429 (e.g., washer, seals, etc.) may be used to position the membrane 428 or modify its elution rate. In some embodiments, the spacers 429 can be of the same material as main body 411 of the implant 410. In some embodiments, the one or more spacers 429 may deform a portion of the membrane 428 to form a compressed portion . In some embodiments, the sealing surfaces formed at the points the compressed portion of the membrane 428 contacts other components of the implant 410 can prevent or substantially prevent elution through those sealing surfaces. Therefore, in some embodiments, the sealing surfaces of the membrane 428 can direct the elution of a treatment therapeutic (e.g., treatment fluid) through the uncompressed portion of the membrane 428, out the proximal end 414 of the implant 410.

[0189] In some embodiments, the spring retainer 440 or spring retainer 440 can reduce or mitigate at least some of the stress or strain exerted on the membrane 428 during compression. In some embodiments, the spring retainer 440 can reduce stress exerted on the membrane 428 that results from the use of the implant 410. In some embodiments, these stresses can result from compression of the membrane 428, expansion of one or more components of the implant 410 (such as the treatment therapeutic (e.g., treatment fluid) within the reservoir 426), formation of a vacuum within the implant 410 as the treatment therapeutic (e.g., treatment fluid) exits the implant 410, and any other factors. In some embodiments, the spring retainer 440 can include a central portion to prevent or substantially prevent severe deformation of a membrane 428 during use of the implant 410. In some embodiments, the spring retainer 440 can be made of polypropylene, polyimide, polyvinyl alcohol, polyethersulfone (PES), poly(styrene-isobutyl-styrene), polyurethane, polyetherether ketone (PEEK), Polytetrafluoroethylene (PTFE), Polymethylmethacrylate (PMMA), acrylic, polyolefin, polydimethylsiloxane and other silicone elastomers, polypropylene, titanium, gold, titanium alloys, stainless steel, cobalt-based alloys, titanium-based alloys, nickel-titanium alloy, tungsten, nickel-chromium-molybdenum alloys, other metals and alloys, ceramics, plastics, polymers, and mixtures or combinations thereof. In some embodiments, the spring retainer 440 is constructed such that one portion of the spring retainer 440 has a different durometer or ductility or elastic modulus or Young’s modulus compared to another portion of the spring retainer 440.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0190] In some embodiments, one or more spacers 429 (e.g., washer, seals, etc.) may be used to position the membrane 428 or modify its elution rate. In some embodiments, the spacers 429 can be of the same material as main body 411 of the implant 410. In some embodiments, the one or more spacers 429 may compress or deform a portion of the membrane 428 to form a compressed portion, similar to how the one or more spacers 429 can deform the membrane 328 to form a compressed portion 328A in some embodiments, as described in connection with Figures 3A-3G.

[0191] In some embodiments, a portion of the main body 411 of the implant 410 can function as the spacer such that no sealing member may be needed between the membrane 428 and the main body 411. In some embodiments, the spacer 429 can be combined with the spring retainer 440 to form a retainer spacer such that no sealing member may be needed between the membrane 428 and the retainer. In some embodiments, the spacers can be incorporated into both the main body and the spring retainer 440 such that no spacer 429 is needed.

[0192] In some embodiments, such as shown in Figures 11A and 11B, the spacer 329, 429 can be combined with the spring retainer 440 to form a retainer spacer 380. The retainer spacer 380 can be configured to deform or expand to accommodate its insertion into a proximal end 414 of an implant 410. In some embodiments, the retainer spacer 380 can resist proximal movement relative to the main body 411 similar to other retainers as disclosed herein. In some embodiments, the retainer spacer 380 can be made of multiple materials such that one portion of the retainer spacer has a different durometer or ductility or elastic modulus or Young’s modulus compared to another portion of the retainer spacer.

[0193] In some embodiments, the spacer portion (e.g., one or more spacers 329, 429) has a greater stiffness as compared to the retainer portion (324, 440). Most simply, it could be the same material but have a greater thickness at the spacer portion. The materials or combinations of materials may be the same as the materials provided above. The spacer portion can be one metal or metal alloy with higher stiffness and the retainer portion can be a metal or metal alloy with less stiffness. Non-limiting examples of stiffer materials include tungsten, cobalt chromium alloys, stainless steel (e.g., 302, 304, 316 stainless steel), nickel-chromium-molybdenum alloy (e.g., Hastelloy, Inconel), cobalt-based alloys (e.g., 35N LT, MP35N alloys). Non-limiting examples of less stiff materials include nickel- chromium-molybdenum alloy (e.g., Hastelloy, Inconel), cobalt-based alloys (i.e. 35N LT,PCT / US25 / 43600 26 August 2025 (26.08.2025)MP35N alloys), titanium Alloys (such as 6AL4V alloy), titanium, and nitinol. Any metal may be a stiff material used with a non-metal less stiff material.

[0194] In some embodiments, the spnng retainer 440 can be configured to interface with a portion of the main body 411 of the implant 410 to substantially prevent proximal movement of the components of the implant 410 once the retainer is installed. Once the reservoir 426 has been filled with the desired quantity of treatment therapeutic (e.g., treatment fluid) and the membrane 428 and one or more spacers 429 have been positioned (if a particular embodiment requires any spacers 429), the spring retainer 440 can be installed in the implant 410 to substantially prevent proximal movement of the components of the implant 410.

[0195] In some embodiments, the spring retainer 440 can comprise one or more features designed to interface with reliefs 413 (e.g., cuts, openings, passageways, retention openings, retention features, grooves, ridges, ribs, lip, etc.) in the proximal end 414 of the main body 411. These features can function as clips that slot into the reliefs 413. In some embodiments, the spring retainer 440 can be configured to partially or substantially deform to allow for assembly or interface of the protrusions with the reliefs 413.

[0196] In some embodiments, the proximal end 414 can be configured such that, after all components (e.g., the main body 411, the membrane 428, one or more spacers 429 if required, etc.) of the implant 410 have been assembled, the spring retainer 440 can be inserted into the proximal end 414 of the main body 411 to prevent proximal movement of the internal components from the main body 411.

[0197] In some embodiments, two reliefs 413 are cut into the proximal end 414. In some embodiments, one, three, four, or more than four reliefs 413 can be cut into the proximal end 414. The reliefs 413 can be part of a coupling structure between the main body 411 and spring retainer 440 and assist in the installation of the spring retainer 440 once the implant 410 is filled with the treatment therapeutic (e.g., treatment fluid) and the various components are arranged. In some embodiments, the reliefs 413 are cut completely through the proximal end 414 of the main body 411. In some embodiments, the reliefs 413 are partial cuts into the surface of the proximal end 414.

[0198] In some embodiments, the outer profile of a retainer can be sized and dimensioned to have a cross-sectional profile that is larger (e.g., wider, longer, etc.) than the cross-sectional profile of the opening to the internal reservoir 426 on the proximal end 414 of the implant 410. For example, the opening to the internal reservoir 426 may have an internal diameter dl and the retainer may have width wl, where wl > dl. In somePCT / US25 / 43600 26 August 2025 (26.08.2025) embodiments, a spring retainer 440 can be made of a flexible material such that, when flexed, can fit within the proximal end 414. The spring retainer 440 can then, when positioned appropriately, return to a less flexed state or an unflexed (e.g., substantially undeformed, un-flexed, substantially un-stressed, etc.) state to properly seat the internal components of the implant 410 within the main body 411.

[0199] The spring retainer 440 can comprise a first portion 442, one or more retention arms 444 (e.g. flexible retention feature, retention feature, flexible retainers, retaining features, retainers, etc.), and a second portion 446. In some embodiments, the spring retainer 440 can have its first portion 442 and second portion 446 sized and dimensioned to, at least partially, fit within and be aligned with the one or more reliefs 413 at the proximal end 414. The spring retainer 440 can have passages or openings to allow treatment therapeutic (e.g., treatment fluid) to elute from the implant 410 once the internal components and the proximal end 414 are installed in the implant 410. The retention arms 444 can assist in aligning the spring retainer 440 with the reliefs 413. In some embodiments, the retention arms 444, when the spring retainer 440 is installed in the implant, exert an outward force (e.g., against an internal wall of the implant 410) to prevent or substantially prevent unintentional disassembly of the implant 410.

[0200] In some embodiments, the spring retainer 440 can reduce or mitigate at least some of the stress or strain exerted on the membrane 428 during compression. In some embodiments, the spring retainer 440 can reduce stress exerted on the membrane 428 that results from the use of the implant 410. In some embodiments, these stresses can result from compression of the membrane 428, expansion of one or more components of the implant 410 (such as the treatment therapeutic (e.g., treatment fluid) within the reservoir 426), formation of a vacuum within the implant 410 as the treatment therapeutic (e.g., treatment fluid) exits the implant 410, and any other factors. In some embodiments, the spring retainer 440 can include a central portion to prevent or substantially prevent severe deformation of a membrane 428 during use of the implant 410.

[0201] In some embodiments, a proximal end of the spring retainer 440 and / or a distal end of the spring retainer 440 can tend from the body of the implant 410. In some embodiments, the proximal end of the spring retainer 440 and / or the distal end of the spring retainer 440 can be flush with the external surface of the body of the spring retainer 440. In some embodiments, the proximal end of the spring retainer 440 and / or the distal end of the spring retainer 440 can be positioned inward relative to the external surface of the body of the spring retainer 440.PCT / US25 / 43600 26 August 2025 (26.08.2025)

[0202] Figures 5A to 5D and Figures 6A to 6D illustrate examples of implants 510, 610 that may include the same or similar structural and functional features as shown and described in connection with the implants of Figures 3 A to 3G and / or Figures 4A to 4F but the reservoir 326 / 426 may include multiple chambers. The multiple chambers may store different therapeutics (e.g., drugs) or the same therapeutic (e.g., drug). In some embodiments, a first drug and a second drug may both be eluted proximally (e.g., form a proximal portion or end of the implant 510). The implants 510, 610 can generally have a main body 311 portion comprising or consisting essentially of a distal end 312 and a proximal end 314, and a retainer 324 portion configured to retain or contain one or more treatment therapeutics within the implant 510, 610. The main body 311 comprises a multichambered reservoir. In one embodiment (as shown in Figures 5A to 5D), the multichambered reservoir may comprise an inner chamber 326A and an outer chamber 326B (e.g., concentric chambers), wherein the inner chamber 326A stores a first drug configured to be eluted proximally and the outer chamber 326B stores a second drug configured to be eluted proximally . In one embodiment (as shown in Figures 6A to 6D), the multichambered reservoir may comprise side-by-side chambers comprising a first chamber 326C and a second chamber 326D, wherein the first chamber 326C stores a first drug configured to be eluted proximally and the second chamber 326D stores a second drug configured to be eluted proximally.

[0203] In some embodiments, a first drug may be eluted proximally and a second drug may be eluted distally either in addition to be eluted proximally or as an alternative. As shown in Figures 7A to 7D and in Figures 8A to 8C, the reservoir 326 may comprise a multi-chambered reservoir. Further, the multi-chambered reservoir may comprise a proximal chamber at a proximal end 314 of the implant 710 and a distal chamber 356 at a distal end 312 of the implant 510, wherein the proximal chamber stores a first drug configured to be eluted proximally and the distal chamber 548 stores a second portion of the first drug or a different, second drug that is configured to be eluted distally. The distal end 312 of the implant 710 includes one or more outlets, apertures, or openings or other elution elements 352 and a membrane 354. The membrane 354 may incorporate any of the structural and / or functional features or aspects of the membranes described herein (e.g., membranes 328, 428) and may facilitate controlled elution over time. The proximal end 314 of the implant 710 may also include a proximal membrane 358 and optionally one or more spacers such as illustrated in the previous figures (e.g., to facilitate controlled drug elution). The implant 810 of Figures 8A to 8C illustrates that the elution elements 352 mayPCT / US25 / 43600 26 August 2025 (26.08.2025) alternatively be positioned along a distal tip extending from a main body of the implant 810. The elution elements 352 may be designed to be in fluid communication with one or more lumens extending from the distal chamber 356. The membrane 354 may have one of a variety of shapes (e.g., a disc shape as shown if Figure 8B or a spherical shape as shown in Figure 8C). The proximal end 314 of the implant 810 may also include a proximal membrane 358 and optionally one or more spacers such as illustrated in the previous figures (e.g., to facilitate controlled drug elution). The unique features (e.g., elution elements 352, distal membrane 354 or chambers) of Figures 7 A to 7D or Figures 8A to 8C may be incorporated in any of the other figures or examples described herein.

[0204] In some embodiments, the reservoir 326 can be a single chamber that elutes a drug or drugs proximally (e.g., through a drug elution element at the proximal end 314) and distally (e.g., through a drug elution element at the distal end 312). Embodiments of drug delivery implants that elute drug or drugs from different regions of the implant may be useful for delivering the drug or drugs to different target locations (e.g., proximally eluting drug into anterior chamber and distally eluting drug through the implant anchor to anchored tissue).

[0205] The implants described herein may include one or more elution elements (e.g., holes, openings, outlets, apertures, or pores) at a proximal end of the implant, at a distal end of the implant, and / or along the main body of the implant. The elution elements may be on a side surface of a reservoir and / or on an end surface of the reservoir. Alternatively, the elution elements may be on an anchor or other distal feature extending from the reservoir (such as shown in Figures 8A and 8B).

[0206] Several embodiments of the implant may also comprise a shunt in addition to functioning as a drug delivery device. The term “shunt” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and it is not to be limited to a special or customized meaning), and refers without limitation to the portion of the implant defining one or more fluid passages for transport of fluid from a first, often undesired location, to one or more other locations. In some embodiments, the shunt can be configured to provide a fluid flow path for draining aqueous humor from the anterior chamber of an eye to an outflow pathway to reduce intraocular pressure, such as is depicted generally in Figure 12. In other embodiments the shunt can be configured to provide a fluid flow path for draining aqueous humor to an outflow pathway. Still other embodiments can be configured to drain ocular fluid or interstitial fluid from the area in and around the eye to a remote location. Yet otherPCT / US25 / 43600 26 August 2025 (26.08.2025) combination drug delivery -shunt implants may be configured to drain physiological fluid from a first physiologic site to a second site (which may be physiologic or external to a patient). In still additional embodiments, the shunt additionally (or alternatively) functions to provide a bulk fluid environment to facilitate the dilution and / or elution of the drug.

[0207] The shunt portion of the implant 1210 can have an inflow portion 390 and one or more outflow portions 392. As described above, the outflow portion 392 may be disposed at or near the proximal end 1152 of the implant. In some embodiments, a shunt outflow portion may be disposed at or near the distal end of the implant with the inflow portion residing a different location (or locations) on the implant. In some embodiments, when the implant is deployed, the inflow portion may be sized and configured to reside in the anterior chamber of the eye and the outflow portion may be sized and configured to reside in the supraciliary or suprachoroidal space. In some embodiments, the outflow portion may be sized and configured to reside in the supraciliary region of the uveoscleral outflow pathway, the suprachoroidal space, other part of the eye, or within other physiological spaces amenable to fluid deposition.

[0208] In some embodiments, at least one lumen extends through the shunt portion of the implant. In some embodiments, there is at least one lumen that operates to conduct the fluid through the shunt portion of the implant. In certain embodiments, each lumen extends from an inflow end to an outflow end along a lumen axis. In some embodiments the lumen extends substantially through the longitudinal center of the shunt. In other embodiments, the lumen can be offset from the longitudinal center of the shunt.

[0209] In implants additionally comprising a shunt in the proximal portion of the device, the first (most proximal) outflow orifice on the implant is positioned between 1 and 10 mm from the anterior chamber of the subject. In some embodiments additionally comprising a shunt in the proximal portion of the device, the first (most proximal) outflow orifice on the implant is positioned preferably between 2 and 5 mm from the anterior chamber of the subject. Additional outflow orifices may be positioned in more distal locations, up to or beyond the point where the interior lumen housing the drug or therapeutic agent begins.

[0210] In some embodiments comprising a shunt, a shunt inflow portion is disposed at or near a proximal end of the implant and a shunt outflow portion is disposed at or near a distal end of the shunt. However, as shown in Figure 12, the shunt inflow portion and the shunt outflow portion may be at or near a distal end of the implant. When implanted, in several embodiments, the shunt inflow portion is sized and configured toPCT / US25 / 43600 26 August 2025 (26.08.2025) reside in the anterior chamber of the eye and the shunt outflow portion is sized and configured to reside in the uveoscleral outflow pathway. In some embodiments, the shunt outflow portion is sized and configured to reside in the supraciliary region of the uveoscleral outflow pathway or in the suprachoroidal space. Multiple outflow points may be used in a single device, depending on the embodiment.Method of Assembly

[0211] In some embodiments, the spring retainer 440 can be inserted into the proximal end 414 of the implant 410 to retain the internal components of the implant 410 according to the following assembly steps:

[0212] First, the first portion 442 can be inserted into the proximal end 414 of an implant 410 at an angle by passing the first portion 442 through a relief 413 cut in the proximal end 414. Figure 4E depicts one embodiment of the present disclosure at this step of installation. Passing the first portion 442 through the relief 413 may deform the one or more retention arms 444 of the spring retainer 440. Deforming the retention arms 444 of the spring retainer 440 generates a spring force to return the spring retainer 440 to its undeformed state (e.g., to move the first portion 442 into the opening on the proximal end 414 and away from the first relief 413). The first portion 442 can be inserted sufficiently into and / or through the first relief 413 such that the second portion 446 can enter the opening in the proximal end 414.

[0213] Once the first portion 442 passes sufficiently through the relief 413, the second portion 446 of the spring retainer 440 can be angled down to be adjacent or in contact with the proximal-most internal component. The second portion 446 would then be within the smaller cross-sectional profile of the proximal end 414. The second portion 446 can in some embodiments compress the internal components of the implant 410 to he flat and align with a second relief 413 on a substantially opposite end of the first relief 413. The reliefs 413 can be spaced equally around the proximal end 414, or not spaced equally around the proximal end 414, depending on the configuration of the spring retainer 440 used in certain embodiments.

[0214] Once the second portion 446 is aligned with the second relief 413, the spring retainer 440 can be released. The stored energy of the deformed retention arms 444 can return the spring retainer 440 to an undeformed or less-deformed state. This movement forces the second portion 446 into the second relief 413, as shown in Figure 4F. Positioning of the spring retainer 440 in such a way thus locks the internal components of the implantPCT / US25 / 43600 26 August 2025 (26.08.2025)410 from accidentally becoming dislodged during an implanting process. The retention arms 444 can bias the first portion 442 and the second portion 446 such that both portions remain substantially engaged with the reliefs 413 in the proximal end 414 of the implant 410.

[0215] The spring retainer 440 can thus limit the proximal movement of the components within the implant 410 in a manner similar to how the retainer 324 limited the proximal movement of components in other implants disclosed herein.

[0216] The spring retainer 440 can impact the elution rate of treatment fluid from the reservoir 426 similarly to the retainer 424 as described herein. In some embodiments, the spring retainer 440 can be dimensioned such that the elution rate of treatment therapeutic (e.g., treatment fluid) is within expected ranges. In some embodiments, the thickness of the membrane 428, the opening size of the one or more spacers 429, or other factors as described herein can be modified to configure the desired release rate for an implant 410 that utilizes a spnng retainer 440 in assembly of the components on the proximal end 414, using methods or teachings similar to how the retainer 324 can be modified to change an elution rate or release rate of a drug or treatment material can be modified. The drug supplied by the implant 410 can passively elute from the implant by passing through the membrane 428 and around the spring retainer 440. The spring retainer 440 can have passages or other openings to allow the treatment therapeutic (e.g., treatment fluid) to exit the proximal end 414 of the implant 410.

[0217] In some embodiments, the implant comprises various features that are present as single features (as opposed to multiple features). For example, in one embodiment, the implant includes a single treatment therapeutic (e.g., treatment fluid) pathway, a single sharpened end, a single lumen, a single retention element, and a single spacer. These features may also be present as multiple features instead of single features.

[0218] In some embodiments, the system comprises one or more of the following: means for providing an implant to the eye of a patient (e.g., an implant insertion apparatus or other type of catheter or delivery device), means for assembling the implant (e.g., an implant assembly apparatus or device), and various other related systems for manufacturing the implants or components of the implants, such as the drug provided or an internal part of the implant.PCT / US25 / 43600 26 August 2025 (26.08.2025)Additional Language

[0219] While certain embodiments of the disclosure have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the disclosure. Indeed, the novel methods, systems, and devices described herein may be embodied in a variety of other forms. For example, embodiments of one illustrated or described implant can be combined with embodiments of another illustrated or described implant. Moreover, the implants described above can be utilized for other purposes. For example, the implants can be used to drain fluid from the anterior chamber to other locations of the eye or outside the eye. In some embodiments, the systems comprise various features that are present as single features (as opposed to multiple features). Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Multiple features or components are provided in some embodiments. Some embodiments have been described in connection with the accompanying drawings. However, it should be understood that the figures are not necessarily drawn to scale. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and / or rearranged. Furthermore, various omissions, substitutions and changes in the form of the methods, systems, and devices described herein may be made without departing from the spirit of the disclosure.

[0220] While drug delivery implants described herein may have been described in the context of primarily treating ocular disorders, the implants may be used for prolonged delivery of therapeutics to treat a variety of indications, including those affecting nonocular tissue. For example, the implants may be anchored to tissue of the cardiovascular system (e.g., heart, arteries, veins, other blood vessels), gastrointestinal system (e.g., stomach, intestines, colon), respiratory system (e.g., nasal cavity, nasal passage, respiratory tract, lungs), lymphatic system, and / or nervous system.

[0221] Conditional language, for example, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and / or steps. Thus, such conditional language is not generally intended to imply that features, elements and / or steps are in any way required for one or more embodiments or that one or more embodiments necessarily include logic for deciding, with or without user input or prompting, whetherPCT / US25 / 43600 26 August 2025 (26.08.2025) these features, elements and / or steps are included or are to be performed in any particular embodiment. The section headings used herein are merely provided to enhance readability and are not intended to limit the scope of the embodiments disclosed in a particular section to the features or elements disclosed in that section. The terms “comprising;’ “including,”, “having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term “or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term “or” means one, some, or all of the elements in the list.

[0222] Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “advancing a delivery apparatus” include “instructing advancing a delivery apparatus.” The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers or an amount that is within less than or equal to 10% of the stated amount. For example, “about 1 millimeter” includes “1 millimeter.” Terms or phrases preceded by a term such as “substantially” or “generally” include the recited term or phrase. The term “generally” as used herein represents a value, amount, or characteristic that predominantly includes or tends toward a particular value, amount, or characteristic. For example, “substantially all of the length” includes “all of the length” and “generally relaxed” includes “relaxed.”

[0223] For purposes of this disclosure, certain aspects, advantages, and novel features are described herein. Not necessarily all such advantages may be achieved in accordance with any particular embodiment. Thus, for example, those skilled in the art will recognize that the disclosure may be embodied or carried out in a manner that achieves one advantage or a group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.

Claims

PCT / US25 / 43600 26 August 2025 (26.08.2025)WHAT IS CLAIMED IS:

1. An implant configured to be implanted in an eye to treat an ocular disorder, the implant comprising: a mam body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of crimping portions; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate; one or more positioning elements configured to position the drug release element; and a retaining element with one or more openings, wherein, when the drug is positioned within the internal reservoir, the one or more positioning elements are inserted into the opening in the proximal end with the drug release element, wherein, when the one or more positioning elements and the drug release element are arranged within the main body, the retaining element is inserted into the opening in the proximal end to form an assembly within the main body, wherein the assembly is compressed such that the plurality of crimping portions impede movement of the assembly from the main body, wherein the drug elutes from the implant by passing through the drug release element and the one or more openings in the retaining element.

2. The implant of Claim 1, wherein the main body further comprises an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

3. The implant of Claim 1 or 2, wherein the distal end of the main body comprises an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

4. The implant of any of Claims 1 to 3, wherein one of the one or more positioning elements is integrally formed with the main body.

5. The implant of any of Claims 1 to 4, wherein one of the one or more positioning elements is integrally formed with the retaining element.

6. The implant of any of Claims 1 to 5, wherein the drug release element comprises an undeformed portion and a deformed portion, the deformed portion being compressed byPCT / US25 / 43600 26 August 2025 (26.08.2025) the one or more positioning elements, wherein the drug elutes from the implant by passing through the undeformed portion of the drug release element.

7. An implant configured to be implanted in an eye to treat an ocular disorder, the implant comprising: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of crimping portions; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate, and a retaining element with one or more openings; wherein, when the drug, the drug release element, and the retaining element are inserted into the opening in the main body, the plurality of crimping portions are configured to be selectively deformed to impede movement of the drug release element and the retaining element from the main body.

8. The implant of Claim 7, further comprising one or more positioning elements configured to position the drug release element within the opening in the main body.

9. The implant of Claim 8, wherein one of the one or more positioning elements is integrally formed with the main body.

10. The implant of Claim 8, wherein one of the one or more positioning elements is integrally formed with the retaining element.

11. The implant of any of Claims 7 to 10, wherein the main body further comprises an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

12. The implant of any of Claims 7 to 11, wherein the distal end of the main body comprises an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

13. An implant configured to be implanted in an eye to treat an ocular disorder, the implant comprising: a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retention reliefs; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate;PCT / US25 / 43600 26 August 2025 (26.08.2025) one or more positioning elements configured to position the drug release element, and a retaining element, the retaining element comprising one or more flexible retention features and one or more fluid passages, the one or more fluid passages allowing fluid flow around the retaining element; wherein, when the drug is positioned within the internal reservoir, the one or more positioning elements are inserted into the opening in the proximal end with the drug release element; wherein, when the one or more positioning elements and the drug release element are arranged within the main body, the retaining element is installed into the main body; wherein the retaining element comprises: a first portion of the retaining element aligned with a first opening of the plurality of retention reliefs; a selectively flexible retaining element having a cross-sectional profile smaller than the cross-sectional profile of the opening; and a second portion of the retaining element aligned with a second opening of the plurality of retention reliefs, wherein the retaining element can return to an unflexed or less flexed state by releasing compression on the retaining element, and wherein the drug is configured to elute from the implant by passing through the drug release element and around the retaining element.

14. The implant of claim 13, wherein allowing the retaining element to return to an unflexed or less flexed state inserts the second portion of the retaining element into the second opening of the plurality of retention reliefs.

15. The implant of Claim 13, wherein the plurality of retention reliefs comprise holes passing through the proximal end of the main body.

16. The implant of Claim 13 to 15, wherein the one or more flexible retention features deform as the retaining element is installed, the one or more flexible retention features configured to assist in aligning the retaining element within the main body.

17. The implant of any of Claims 13 to 16, wherein the main body further comprises an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.PCT / US25 / 43600 26 August 2025 (26.08.2025)18. The implant of any of Claims 13 to 17, wherein the distal end of the main body comprises an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

19. The implant of any of Claims 13 to 18, wherein one of the one or more positioning elements is integrally formed with the main body.

20. The implant of any of Claims 13 to 19, wherein one of the one or more positioning elements is integrally formed with the retaining element.

21. The implant of Claim 13, wherein the plurality of retention reliefs comprise one or more of openings, grooves, or ridges.

22. The implant of any of Claims 13 to 21, wherein the retaining element comprises a cross-sectional profile larger than a cross-sectional profile of the opening to the internal reservoir.

23. The implant of any of Claims 13 to 20, wherein the drug release element comprises an uncompressed portion and a compressed portion, the compressed portion being compressed by the one or more positioning elements, wherein the drug elutes from the implant by passing through the uncompressed portion of the drug release element.

24. The implant of any of Claims 13 to 23, wherein the internal reservoir has a volume between 100 nL to 500 nL.

25. The implant of any of Claims 13 to 24, wherein has a release rate between 25 ng / day to 250 ng / day.

26. The implant of any of Claims 13 to 25, wherein the drug is travoprost.

27. An implant configured to be implanted in an eye to treat an ocular disorder, the implant comprising: a mam body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retaining features; a drug positioned within the internal reservoir; a drug release element configured to passively release the drug from the internal reservoir to an ocular fluid at a release rate, and a flexible retaining element with one or more fluid passages; wherein, when the drug, the drug release element, and the flexible retaining element are inserted into the opening in the main body, the flexible retaining element is configured to deform and interface with the plurality of retaining featuresPCT / US25 / 43600 26 August 2025 (26.08.2025) in the main body to impede movement of the drug release element and the flexible retaining element from the main body.

28. The implant of Claim 27, wherein installation of the flexible retaining element comprises: inserting a first portion of the flexible retaining element into a first opening of the plurality of retaining features; selectively deforming the flexible retaining element to have a cross- sectional profile smaller than the cross-sectional profile of the opening; aligning a second portion of the flexible retaining element with a second opening of the plurality of retaining features; and allowing the flexible retaining element to return to an undeformed state by releasing compression on the flexible retaining element, wherein allowing the flexible retaining element to return to an undeformed state inserts the second portion of the flexible retaining element into the second opening of the plurality of retaining features.

29. The implant of Claim 27 or 28, wherein the drug elutes from the implant by passing through the drug release element and around the flexible retaining element.

30. The implant of any of Claims 27 to 29, wherein the plurality of retaining features comprise holes passing through the proximal end of the main body.

31. The implant of any of Claims 27 to 30, wherein the flexible retaining element further comprises one or more flexible retention features, wherein the one or more flexible retention features deform as the flexible retaining element is installed, the one or more flexible retention features configured to assist in aligning the flexible retaining element within the main body.

32. The implant of any of Claims 27 to 31, wherein the main body further comprises an interface feature, wherein the implant is positioned within the eye with an implant applicator removably connected to the interface feature of the implant.

33. The implant of any of Claims 27 to 32, further comprising one or more positioning elements configured to position the drug release element within the opening in the main body.

34. The implant of Claim 33, wherein one of the one or more positioning elements is integrally formed with the main body.

35. The implant of any of Claims 33 to 34, wherein one of the one or more positioning elements is integrally formed with the flexible retaining element.PCT / US25 / 43600 26 August 2025 (26.08.2025)36. The implant of any of Claims 27 to 35, wherein the distal end of the main body comprises an implant connection end, the implant connection end configured to pass at least partially through a target ocular tissue and stably retain the implant at the target ocular tissue.

37. A method of assembling an implant configured to treat an ocular disorder, the method comprising: obtaining a main body having a proximal end and a distal end, the proximal end having an opening to an internal reservoir and a plurality of retention elements, the distal end having an implant connection end; providing a drug to the internal reservoir; positioning one or more positioning elements in the opening in the proximal end with a drug release element, such that the one or more positioning elements are contacting the drug release element; positioning a retaining element in the opening in the proximal end adjacent a positioning element; compressing the one or more positioning elements, the drug release element, and the retaining element such that a proximal most surface of the retaining element is below a distal most surface of the plurality of retention elements; and retaining the one or more positioning elements, the drug release element, and the retaining element to the main body.

38. The method of Claim 37, wherein retaining the one or more positioning elements, the drug release element, and the retaining element to the main body comprises deforming the proximal end adjacent the plurality of retention elements to reduce a size of the opening such that the retaining element cannot exit the opening.

39. The method of Claim 37, wherein retaining the one or more positioning elements, the drug release element, and the retaining element to the main body comprises: inserting a first portion of the retaining element into a first portion of the plurality of retention elements; selectively deforming the retaining element to have a cross-sectional profile smaller than a cross-sectional profile of the opening; aligning a second portion of the retaining element with a second portion of the plurality of retention elements; and allowing the retaining element to return to an undeformed state by releasing compression on the retaining element, wherein allowing the retaining element toPCT / US25 / 43600 26 August 2025 (26.08.2025) return to the undeformed state inserts the second portion of the retaining element into the second portion of the plurality of retention elements.

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