Superior choroidal implantable device and method for treating intraocular hypertension

Abstract

A suprachoroidal implantable device formed from a compatible material has an outer surface and an inner surface on the opposite side, and exhibits an outer and inner surface with variable porosity extending through the compatible material, or with different porosity. The surface of the compatible material either promotes or inhibits the internal growth of tissue into the material. The device and the method of using the device reduce intraocular pressure by directing a fluid through the compatible material.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 471,916, filed on June 8, 2023, and U.S. Provisional Application No. 63 / 657,028, filed on June 6, 2024, and the entire contents of these applications are incorporated herein by reference for all purposes.

[0002] Field The present disclosure generally relates to devices and methods for treating ocular hypertension. More specifically, the present disclosure relates to devices and methods for treating ocular hypertension via suprachoroidal implants.

Background Art

[0003] Background ​​​​​​​​For example, implantable stents such as CyPass® stent (Alcon Inc.), iStent Supra® stent (Glaukos Corp.), MINIject® stent (iSTAR Medical), and BioStent® (Iantrek, Inc.) are part of the types of minimally invasive ab-interno choroidal stents that have been used in the past. See Ianchulev et al. (2024) "Biotissue stents for the superior ciliary outflow tract in patients with open-angle glaucoma: Surgical procedure and initial clinical results of aqueous humor drainage biostents" British Journal of Ophthalmology, January 29, 2024, 108(2), 217-222 doi: 10.1136 / bjo-2022-322536. PMID: 36593090; PMCID: This is summarized in PMC10850681 (hereinafter referred to as "Ianchulev et al."). As Ianchulev et al. explain, CyPass® stents and iStent Supra® stents are rigid, non-conforming, impermeable, and non-hydrophilic, while MINIject® stents and BioStent® stents are porous, hydrophilic, and permeable.

[0006] Initial treatment for glaucoma generally focuses on improving existing aqueous humor outflow pathways, including both conventional (tracheal) and non-conventional (uveoscleral) pathways. When these treatments are ineffective, or when a patient's glaucoma becomes unresponsive to treatment, the condition is called refractive glaucoma, and glaucoma drainage implants are often used. [Overview of the Initiative]

[0007] summary This specification discloses suprachoroidal implantable devices and methods for controlling intraocular fluid pressure. Advantages of such devices and methods include controlling internal tissue growth relative to the outer surface of the implantable device. In some examples, the internal volume of the implantable device is adjustable in situ, and the internal volume can be controlled without removing the device from the implantation site. In some examples, the devices and methods disclosed herein offer the advantage of minimizing or inhibiting the progression of fibrosis in the tissue surrounding the implant, thereby inhibiting internal growth from the surrounding tissue through the device, particularly the inner surface of the device. In various examples, the device's reservoir or internal volume remains free from internal tissue growth. In some examples, the outer surface allows for internal tissue growth, securing the device at the implantation site and / or supporting the surrounding tissue. These devices are flexible and can cause little to no discomfort to the patient after the implantation procedure. In various embodiments, the device can exert an outward force on the external tissue of the eye at the site of implantation. Such an outward force can help maintain a secondary drainage pathway for aqueous humor to flow out of the anterior chamber of the eye. This sustained flow can help lower intraocular pressure (IOP) when, for example, the primary drainage pathway is blocked.

[0008] According to one example ("Example 1"), the suprachoroidally implantable device includes a body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of a body portion having a fixed volume. When the outer and inner surfaces are observed at a magnification selected from 50x to 1000x, the outer surface has surface features minimally present on the inner surface. Alternatively, in several related examples, the outer surface is characterized by surface features present minimally on the inner surface, and furthermore, the surface features are less visible on the inner surface than on the outer surface, and in some cases, the surface features are visible on the outer surface at 50x magnification but are not visible on the inner surface at 50x magnification; in some cases, the surface features are visible on the outer surface at 100x magnification but are not visible on the inner surface at 100x magnification; in some cases, the surface features are visible on the outer surface at 500x magnification but are not visible on the inner surface at 500x magnification; and in some cases, the surface features are visible on the outer surface at 1000x magnification but are not visible on the inner surface at 1000x magnification.

[0009] In addition to Example 1, according to another example ("Example 2"), the surface features of the outer surface include a plurality of solid portions and a plurality of porous portions. The porous portions include pores ranging in size from 5 μm to 100 μm, and these pores are uniformly distributed among the solid portions.

[0010] In addition to Example 2, according to another example ("Example 3"), the pore portion is flexible so that the pores can be expanded, for example, under physiological conditions.

[0011] In addition to Example 1, according to another example ("Example 4"), the surface features include surface roughness, and the surface roughness of the outer surface is greater than the surface roughness of the inner surface.

[0012] In addition to Example 1, according to another example ("Example 5"), the surface features include a maximum depth, and the maximum depth of the surface features on the outer surface is greater than the maximum depth of the surface features on the inner surface.

[0013] In addition to Example 1, according to another example ("Example 6"), the surface features are defined by a microstructure defined by a plurality of fibrils extending between a plurality of nodes, and furthermore, the microstructure is more visible on the outer surface than on the inner surface.

[0014] In addition to Example 1, according to another example ("Example 7"), the main body portion is formed from a material having a microstructure defined by multiple fibers.

[0015] In another example ("Example 8"), the suprachoroidally implantable device includes a body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of a body portion having a fixed volume. The outer surface has a plurality of openings no larger than 100 μm in size that are not visually observable on the inner surface at magnifications such as 50x to 1000x selected from a range of 50x to 1000x. Alternatively, in some related examples, the outer surface has a plurality of openings no larger than 100 μm in size that are not visually observable at 50x, optionally 100x, optionally 500x, and optionally 1000x.

[0016] In addition to Example 8, according to another example ("Example 9"), the opening is defined by multiple fibrils extending between multiple nodes.

[0017] In addition to Example 8, according to another example ("Example 10"), the opening is defined by multiple fibers.

[0018] In addition to Example 10, according to another example ("Example 11"), the plurality of fibers include a spunbond polymer.

[0019] In addition to any one of Examples 1-11, another example ("Example 12") states that the inner surface inhibits internal growth of the tissue through it.

[0020] According to another example ("Example 13"), the suprachoroidal implantable device includes a body portion formed from a conformable material having an outer surface and an inner surface that defines an internal reservoir of the body portion having a fixed volume. The body portion has a variable porosity that transitions from a first porosity located near the outer surface to a second porosity smaller than the first porosity and located near the inner surface. The first porosity promotes the internal growth of tissue more than the second porosity. Optionally, the first porosity promotes the internal growth of tissue at the outer surface, and the second porosity inhibits the internal growth of tissue through the inner surface.

[0021] According to another example ("Example 14"), the suprachoroidal implantable device includes a body portion formed from a conformable material having an outer surface and an inner surface that defines an internal reservoir of the body portion having a fixed volume. The outer surface has a first porosity, and the inner surface has a second porosity smaller than the first porosity. The first porosity promotes the internal growth of tissue more than the second porosity. Optionally, the first porosity promotes the internal growth of tissue at the outer surface, and the second porosity inhibits the internal growth of tissue through the inner surface.

[0022] In addition to Example 13 or 14, according to another example ("Example 15"), the first porosity is defined by a first average pore size, and the second porosity is defined by a second average pore size smaller than the first average pore size.

[0023] In addition to any one of Examples 1 to 15, according to another example ("Example 16"), the outer surface is a tissue engagement surface.

[0024] In addition to Example 16, according to another example ("Example 17"), the tissue engagement surface has porosity that extends into the engagement surface at an engagement depth at which external tissue engages to fix or anchor the body portion to the suprachoroidal region of the eye where the device was implanted.

[0025] In addition to Example 17, according to another example ("Example 18"), the porosity is selected such that after 30 days, external tissue is observed to engage the engagement surface at the engagement depth.

[0026] In addition to Example 17 or 18, according to another example ("Example 19"), engagement between the tissue engagement surface and the external tissue inhibits migration of the device from the suprachoroidal site.

[0027] In addition to any one of Examples 17 - 19, according to another example ("Example 20"), ingrowth of external tissue at the tissue engagement surface does not significantly inhibit fluid flow through the body portion.

[0028] In addition to any one of Examples 1 - 20, according to another example ("Example 21"), the body portion is pre - sealed to maintain a fixed volume of the internal reservoir.

[0029] In addition to any one of Examples 1 - 21, according to another example ("Example 22"), the conformable material includes expanded polytetrafluoroethylene (ePTFE).

[0030] In addition to any one of Examples 1 - 22, according to another example ("Example 23"), the internal reservoir includes a filling material encapsulated therein.

[0031] In addition to Example 23, according to another example ("Example 24"), the filling material includes ePTFE or a hydrogel.

[0032] In addition to Example 23, according to another example ("Example 25"), the filling material includes a drug, optionally a drug selected to pass through the conformable material from the inner surface to the outer surface over 30 days.

[0033] In another example ("Example 26"), the suprachoroidally implantable device includes a body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the body portion, the internal reservoir having an internal volume that can be adjusted in situ. When the outer surface and the inner surface are observed at a magnification such as, for example, a magnification selected from the range of 50x to 1000x, the outer surface is less uniform than the inner surface. Alternatively, in some related examples, when the outer surface and the inner surface are observed at a magnification of 50x, possibly 100x, possibly 500x, and possibly 1000x, the outer surface may be observed to be less uniform than the inner surface.

[0034] In another example ("Example 27"), a suprachoroidally implantable device includes a body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the body portion, the internal reservoir having an internal volume that is adjustable in situ. The body portion has variable porosity, transitioning from a first porosity located near the outer surface to a second porosity smaller than the first porosity and located near the inner surface. The first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits internal tissue growth through the inner surface.

[0035] According to another example ("Example 28"), a suprachoroidally implantable device includes a body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the body portion, the internal reservoir having an internal volume that can be adjusted in situ. The outer surface has a first degree of porosity, and the inner surface has a second degree of porosity that is smaller than the first degree of porosity. The first degree of porosity promotes internal tissue growth on the outer surface, and the second degree of porosity inhibits internal tissue growth through the inner surface.

[0036] In addition to Examples 27 or 28, according to another example ("Example 29"), the first porosity is defined by a first average pore size, and the second porosity is defined by a second average pore size that is smaller than the first average pore size.

[0037] In addition to any one of Examples 26-29, according to another example ("Example 30"), the outer surface is a tissue engagement surface.

[0038] In addition to Example 30, according to another example ("Example 31"), the tissue engagement surface has porosity extending within the engagement surface to an engagement depth in which external tissue engages in order to fix or anchor the main body portion to the suprachoroidal region of the eye in which the device is implanted.

[0039] In addition to Example 31, according to another example ("Example 32"), the porosity is selected so that after 30 days, it can be observed that the external tissue is engaged with the engagement surface at the engagement depth.

[0040] In addition to Example 31 or 32, according to another example ("Example 33"), the engagement of the tissue engagement surface with the external tissue prevents the device from migrating away from the suprachoroidal region under physiological conditions.

[0041] In addition to any one of Examples 31-33, another example ("Example 34") states that the internal growth of external tissue on the tissue engagement surface does not significantly obstruct the fluid flow through the main body portion.

[0042] In addition to any one of Examples 26-34, according to another example ("Example 35"), the main body is sealed in advance before the implantation procedure of the device.

[0043] In addition to any one of Examples 26-35, according to another example ("Example 36"), the main body portion includes ePTFE.

[0044] In addition to any one of Examples 26-36, according to another example ("Example 37"), the main body portion has a maximum internal capacity and is partially pre-filled to less than the maximum internal capacity to define the internal volume.

[0045] In addition to Example 37, according to another example ("Example 38"), the main body portion is partially pre-filled with filler material to fill at least 10% of the maximum internal volume of the internal reservoir.

[0046] In addition to Example 38, according to another example ("Example 39"), the filler material includes ePTFE, hydrogel, or a combination thereof.

[0047] In addition to Example 38, according to another example ("Example 40"), the filler material comprises a drug, optionally selected to pass through the compatible material from the inner surface to the outer surface over a period of 30 days, or in another manner.

[0048] In addition to any one of Examples 26–40, according to another example ("Example 41"), the device further includes a sealable conduit having a first end and a second end fluidly coupled to the internal reservoir in order to facilitate in-situ adjustment of the internal volume of the internal reservoir.

[0049] In addition to Example 41, according to another example ("Example 42"), the main body portion and the sealable conduit include ePTFE.

[0050] In addition to Examples 41 or 42, according to another example ("Example 43"), the first end of the sealable conduit can be positioned in the subconjunctival region of the eye, and the first end can be sealed after in-situ adjustment of the internal volume.

[0051] In addition to Example 43, another example ("Example 44") shows that the subconjunctival region is located between the conjunctival tissue and the scleral tissue of the eye.

[0052] In addition to Example 41, according to another example ("Example 45"), the first end of the sealable conduit can be positioned within the anterior chamber (AC) of the eye.

[0053] In addition to Example 45, according to another example ("Example 46"), the first end can be sealed after field adjustment of the internal volume.

[0054] In addition to Example 45, according to another example ("Example 47"), the first end of the sealable conduit is left open to facilitate on-site adjustment of the internal volume of the internal reservoir.

[0055] In another example ("Example 48"), the suprachoroidally implantable device includes a body portion having a closed end and an open end that can be fluidly coupled to the anterior chamber (AC) of the eye. The body portion includes a first surface and a second surface located opposite the first surface, and when the first surface and the second surface are observed at a magnification such as, for example, a magnification selected from the range of 50x to 1000x, the second surface is less uniform than the first surface. Alternatively, in several related examples, when the first surface and the second surface are observed at a magnification of 50x, possibly 100x, possibly 500x, and possibly 1000x, the second surface is observed to be less uniform than the first surface.

[0056] According to another example ("Example 49"), a suprachoroidal implantable device includes a body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye. The body portion includes a first surface and a second surface, and the body portion has variable porosity that transitions from a first porosity located near the first surface to a second porosity located near the second surface and smaller than the first porosity. The first porosity promotes internal tissue growth on the first surface, and the second porosity inhibits internal tissue growth through the second surface.

[0057] In another example ("Example 50"), a suprachoroidally implantable device includes a body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye. The body portion includes a first surface and a second surface, the first surface having a first porosity and the second surface having a second porosity smaller than the first porosity. The first porosity promotes internal tissue growth on the first surface, and the second porosity inhibits internal tissue growth through the second surface.

[0058] In addition to Examples 49 or 50, according to another example ("Example 51"), the first porosity is defined by a first average pore size, and the second porosity is defined by a second average pore size smaller than the first average pore size.

[0059] In addition to any one of Examples 48-51, according to another example ("Example 52"), the outer surface is a tissue engagement surface.

[0060] In addition to Example 52, according to another example ("Example 53"), the tissue engagement surface is porous to a depth that allows external tissue to engage in order to fix or anchor the main body portion to the suprachoroidal region of the eye in which the device is implanted.

[0061] In addition to Example 53, according to another example ("Example 54"), the engagement between the tissue engagement surface and the external tissue is observable after 30 days.

[0062] In addition to Examples 53 or 54, according to another example ("Example 55"), the engagement between the tissue engagement surface and the external tissue inhibits migration of the device from the upper choroidal portion.

[0063] In addition to any one of Examples 53-55, another example ("Example 56") states that the internal growth of the external tissue on the tissue engagement surface does not significantly obstruct the fluid flow through the main body portion.

[0064] In addition to any one of Examples 48-56, according to another example ("Example 57"), the main body portion includes ePTFE.

[0065] In addition to any one of Examples 48-57, according to another example ("Example 58"), the main body portion is substantially hollow.

[0066] In addition to any one of Examples 48-58, according to another example ("Example 59"), the main body portion facilitates fluid communication from the second surface to the first surface in response to the fluid pressure applied from the AC.

[0067] In addition to Example 59, according to another example ("Example 60"), the fluid from AC can be dispersed to external parts of the eye via the first surface.

[0068] In addition to Example 60, according to another example ("Example 61"), the external region is between the conjunctival and scleral tissues of the eye.

[0069] In addition to any one of Examples 48 to 61, according to another example ("Example 62"), the main body portion is a tubular structure having a first end and a second end, wherein the first end is closed to form the closed end of the main body portion, and the second end is held in an open configuration to form the open end of the main body portion.

[0070] In addition to Example 62, according to another example ("Example 63"), the first end of the tubular structure is closed by clamping it.

[0071] In addition to any one of Examples 48-63, according to another example ("Example 64"), the main body comprises an internal region and an external region configured to be in direct contact with the external tissues within the eye, wherein the second surface covers the entire internal region and a portion of the external region, and the first surface covers the remaining portion of the external region.

[0072] In addition to any one of Examples 48-64, according to another example ("Example 65"), the main body portion has a substantially circular cross-section.

[0073] In addition to any one of Examples 48-64, according to another example ("Example 66"), the main body portion has a substantially oval or rounded rectangular cross-section.

[0074] In addition to Example 66, according to another example ("Example 67"), when no external force is acting, the main body portion has a first configuration having a first height and a first width, and in response to an external force applied to the main body portion, the main body portion has a second configuration having a second height and a second width, the second height being lower than the first height and the second width being greater than the first width.

[0075] In addition to Example 67, according to another example ("Example 68"), the main body portion reversibly transitions between the first configuration and the second configuration depending on whether or not an external force is applied to the main body portion.

[0076] In addition to any one of Examples 48-67, according to another example ("Example 69"), the main body portion includes an external microporous layer and an internal elastic support structure disposed within the external microporous layer and defining an internal space. The external microporous layer defines both the first surface and the second surface, and furthermore, the internal elastic support structure has a third degree of porosity.

[0077] In addition to Example 69, according to another example ("Example 70"), the third porosity is greater than the first and second porosity, promoting fluid communication between the internal space and the second surface.

[0078] Another example ("Example 71") discloses a method for controlling intraocular fluid pressure. This method includes providing a suprachoroidal implantable device having a body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir having a fixed volume, and positioning the device in the subconjunctival region of the eye. When the outer surface and the inner surface are observed at a magnification such as, for example, a magnification selected from the range of 50x to 1000x, the outer surface is less uniform than the inner surface. Alternatively, in some related examples, when the outer surface and the inner surface are observed at a magnification of 50x, optionally 100x, optionally 500x, and optionally 1000x, respectively, the outer surface is observed to be less uniform than the inner surface. This method also includes controlling intraocular fluid pressure by directing a fluid through the compatible material.

[0079] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 72"). This method includes providing a suprachoroidal implantable device having a body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir having a fixed volume, wherein the body portion has variable porosity transitioning from a first porosity located near the outer surface to a second porosity smaller than the first porosity and located near the inner surface, positioning the device in the subconjunctival region of the eye, and controlling intraocular fluid pressure by directing fluid through the compatible material. The first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits, and possibly prevents, internal tissue growth through the inner surface.

[0080] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 73"). This method includes providing a suprachoroidal implantable device having a main body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir of a fixed volume, wherein the outer surface has a first porosity and the inner surface has a second porosity smaller than the first porosity, positioning the device in the subconjunctival region of the eye, and controlling intraocular fluid pressure by directing fluid through the compatible material. The first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits, and possibly prevents, internal tissue growth through the inner surface.

[0081] Another example ("Example 74") discloses another method for controlling intraocular fluid pressure. This method includes providing a suprachoroidal implantable device having a main body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir having an internal volume; positioning the device in the subconjunctival portion of the eye, wherein the outer surface is less uniform than the inner surface when the outer and inner surfaces are observed at a magnification selected from 50x to 1000x (or, in some related examples, the outer surface may be observed to be less uniform than the inner surface when the outer and inner surfaces are observed at magnifications of 50x, optionally 100x, optionally 500x, and optionally 1000x, respectively); adjusting the internal volume of the internal reservoir in situ; and controlling intraocular fluid pressure by directing fluid through the compatible material.

[0082] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 75"). This method includes providing a suprachoroidal implantable device having a body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir having an internal volume, wherein the body portion has variable porosity transitioning from a first porosity located near the outer surface to a second porosity located near the inner surface and smaller than the first porosity, wherein the internal volume of the internal reservoir is adjusted in situ, and controlling intraocular fluid pressure by directing fluid through the compatible material.

[0083] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 76"). This method includes providing a suprachoroidal implantable device having a main body portion formed from a compatible material and having an outer surface and an opposite inner surface defining an internal reservoir having an internal volume, wherein the outer surface has a first porosity and the inner surface has a second porosity smaller than the first porosity, positioning the device in the subconjunctival portion of the eye, wherein the first porosity promotes internal tissue growth on the outer surface and the second porosity inhibits internal tissue growth through the inner surface, adjusting the internal volume of the internal reservoir in situ, and controlling intraocular fluid pressure by directing fluid through the compatible material.

[0084] In addition to any one of Examples 74-76, according to another example ("Example 77"), the method includes providing a sealable conduit having a first end and a second end, fluidly connecting the second end of the sealable conduit to an internal reservoir of the device, wherein the sealable conduit facilitates in-situ adjustment of the internal volume of the internal reservoir, and positioning the first end of the sealable conduit between the conjunctival and scleral tissues of the eye, or within the anterior chamber (AC) of the eye.

[0085] In addition to Example 77, according to another example ("Example 78"), positioning the first end of the sealable conduit between the conjunctival and scleral tissues of the eye, or within the anterior chamber (AC) of the eye, further includes sealing the first end of the conduit and obstructing fluid communication through it.

[0086] In addition to Example 78, according to another example ("Example 79"), positioning the first end of the sealable conduit in the eye's AC further includes fluidically coupling the AC with the first end of the conduit, thereby facilitating fluid communication from the inner surface to the outer surface in response to the fluid pressure applied from the AC.

[0087] Another example ("Example 80") discloses another method for controlling intraocular fluid pressure. This method includes providing a suprachoroidal implantable device having a body portion having a closed end and an open end, wherein the body portion includes a first surface and a second surface on the opposite side, positioning the device in the subconjunctival region of the eye such that the open end of the device is fluidically coupled to the anterior chamber (AC) of the eye, and controlling intraocular fluid pressure by directing fluid through the first and second surfaces. The first surface is less uniform than the second surface when the first and second surfaces are observed at magnifications selected from 50x to 1000x, respectively. Or, in some related examples, the first surface may be observed to be less uniform than the second surface when the first and second surfaces are observed at magnifications of 50x, optionally 100x, optionally 500x, and optionally 1000x, respectively.

[0088] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 81"). This method includes providing a suprachoroidal implantable device having a body portion having a closed end and an open end, wherein the body portion has a first surface and a second surface on the opposite side, and the body portion has variable porosity transitioning from a first porosity located near the first surface to a second porosity smaller than the first porosity located near the second surface, positioning the device in the subconjunctival region of the eye such that the open end of the device is fluidically coupled to the anterior chamber (AC) of the eye, and controlling intraocular fluid pressure by directing fluid through the first and second porosities. The first porosity promotes internal tissue growth on the first surface, and the second porosity inhibits internal tissue growth through the second surface.

[0089] Another method for controlling intraocular fluid pressure is disclosed in another example ("Example 82"). This method includes providing a suprachoroidal implantable device having a body portion having a closed end and an open end, wherein the body portion has a first surface and a second surface on the opposite side, the first surface having a first porosity and the second surface having a second porosity smaller than the first porosity, positioning the device in the subconjunctival region of the eye such that the open end of the device is fluidically coupled to the anterior chamber (AC) of the eye, and controlling intraocular fluid pressure by directing fluid through the first and second porosities. The first porosity promotes internal tissue growth on the first surface, and the second porosity inhibits internal tissue growth through the second surface.

[0090] Another example ("Example 83") discloses a method for manufacturing an implantable suprachoroidal device. This method includes providing a compatible material, forming a body portion using the compatible material such that the body portion includes an outer surface and an inner surface, wherein the outer surface is less uniform than the inner surface at magnifications of about 50 to 1000 times to promote internal tissue growth (or, in some related examples, the outer surface may be observed to be less uniform than the inner surface when the outer surface and the inner surface are observed at magnifications of 50, optionally 100, optionally 500, and optionally 1000 times, respectively), and providing a filler material in the body portion to define an internal reservoir of fixed volume.

[0091] Another example ("Example 84") discloses another method for manufacturing a suprachoroidally implantable device. This method includes providing a compatible material, forming a body portion using the compatible material such that the body portion includes an outer surface and an inner surface, wherein the body portion has variable porosity transitioning from a first porosity located near the outer surface to a second porosity located near the inner surface that is smaller than the first porosity, and providing a filler material in the body portion to define an internal reservoir of a fixed volume.

[0092] Another example ("Example 85") discloses another method for manufacturing a suprachoroidal implantable device. This method includes: preparing a compatible material having a first surface having a first porosity and a second surface having a second porosity smaller than the first porosity; forming a body portion using the compatible material such that the body portion includes an outer surface and an inner surface, wherein the outer surface has a first porosity that promotes internal tissue growth on the outer surface and the inner surface has a second porosity that inhibits internal tissue growth through the inner surface; and providing a filler material in the body portion so as to define an internal reservoir having a fixed volume.

[0093] Another example ("Example 86") discloses another method for manufacturing a suprachoroidal implantable device. This method comprises preparing a compatible material and forming a body portion using the compatible material, including an outer surface and an inner surface, wherein the outer surface is less uniform than the inner surface at magnifications of about 50x to about 1000x to promote internal tissue growth (or, in some related examples, when the outer surface and the inner surface are observed at magnifications of 50x, optionally 100x, optionally 500x, and optionally 1000x, respectively, the outer surface may be observed to be less uniform than the inner surface). The inner surface defines an internal reservoir having an internal volume that can be adjusted in situ.

[0094] Another example ("Example 87") discloses another method for manufacturing a suprachoroidally implantable device. This method includes: preparing a compatible material having a first surface having a first porosity and a second surface having a second porosity smaller than the first porosity; forming a body portion using the compatible material such that the body portion includes an outer surface and an inner surface, wherein the body portion has variable porosity transitioning from a first porosity located near the outer surface to a second porosity located near the inner surface that is smaller than the first porosity, and the inner surface defines an internal reservoir having an internal volume that can be adjusted in situ.

[0095] Another example ("Example 88") discloses another method for manufacturing a suprachoroidal implantable device. This method includes preparing a compatible material having a first surface having a first porosity and a second surface having a second porosity lower than the first porosity, and forming a body portion using the compatible material such that the body portion includes an outer surface and an inner surface. The outer surface has a first porosity that promotes internal tissue growth on the outer surface, the inner surface has a second porosity that inhibits internal tissue growth through the inner surface, and the inner surface defines an internal reservoir having an internal volume that can be adjusted in situ.

[0096] In addition to any one of Examples 86-88, according to another example ("Example 89"), this method involves providing a sealable conduit having a first end and a second end fluidly coupled to an internal reservoir, thereby facilitating the adjustment of the internal volume of the internal reservoir in situ.

[0097] Another example ("Example 90") discloses another method for manufacturing a suprachoroidal implantable device. This method includes winding a conforming material around a mandrel and heat-treating the conforming material to form a body portion having a closed end and an open end configured to fluidly couple with the anterior chamber (AC) of the eye. The body portion includes a first surface and a second surface, the first surface being less uniform than the second surface at magnifications of about 50x to about 1000x to promote internal tissue growth. Alternatively, in some related examples, when the first surface and the second surface are observed at magnifications of 50x, optionally 100x, optionally 500x, and optionally 1000x, respectively, the first surface may be observed to be less uniform than the second surface.

[0098] Another example ("Example 91") discloses another method for manufacturing a suprachoroidally implantable device. This method includes winding a conforming material around a mandrel and heat-treating the conforming material to form a body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye. The body portion includes a first surface and a second surface, the body portion having variable porosity that transitions from a first porosity located near the first surface to a second porosity located near the second surface and smaller than the first porosity, the first surface having a first porosity that promotes internal tissue growth on the first surface of the body portion, and the second surface having a second porosity that inhibits internal tissue growth through the second surface of the body portion.

[0099] Another example ("Example 92") discloses another method for manufacturing a suprachoroidal implantable device. This method includes winding a compatible material having a first surface having a first porosity and a second surface having a second porosity smaller than the first porosity around a mandrel, and heat-treating the compatible material to form a body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye, wherein the body portion includes a first surface and a second surface, the first surface having a first porosity that promotes internal tissue growth on the first surface of the body portion, and the second surface having a second porosity that inhibits internal tissue growth on the second surface of the body portion.

[0100] In addition to any one of Examples 90-92, according to another example ("Example 93"), the method further includes winding a secondary compatible material around the mandrel before winding the compatible material around the mandrel. Winding the compatible material around the mandrel includes winding the compatible material around the secondary compatible material. Furthermore, heat treatment of the compatible material includes heat treatment of the compatible material to form an outer microporous layer, wherein the outer microporous layer defines both the first surface and the second surface of the body portion, and heat treatment of the secondary compatible material to form an internal elastic support structure that is located within the outer microporous layer and defines an internal space, wherein the internal elastic support structure has a third porosity higher than the first and second porosities, and facilitates fluid communication between the internal space and the second surface.

[0101] In another example ("Example 94"), a method for reducing the fluid pressure of an intraocular fluid includes placing a suprachoroidally implantable device in the subconjunctival region of the eye, wherein the device has a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir of the device having a fixed volume, and when both the outer and inner surfaces are observed at a magnification selected from 50 to 1000 times, the outer surface is less uniform than the inner surface, and the fluid pressure is reduced by transporting the fluid from a high-pressure position to a low-pressure position of the eye through the compatible material.

[0102] In another example ("Example 95"), a method for reducing the fluid pressure of an intraocular fluid includes placing a suprachoroidal implantable device in the subconjunctival region of the eye, wherein the device has a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir of the device having a fixed volume, the compatible material having variable porosity transitioning from a first porosity located near the outer surface to a second porosity located near the inner surface and smaller than the first porosity, the first porosity promoting internal tissue growth toward the outer surface and the second porosity inhibiting internal tissue growth toward the inner surface, and reducing the fluid pressure by transporting the fluid through the compatible material from a high-pressure position to a low-pressure position of the eye.

[0103] In another example ("Example 96"), a method for reducing the fluid pressure of an intraocular fluid includes placing an upper choroidal implantable device in the subconjunctival region of the eye, wherein the device has a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir of the device having a fixed volume, the outer surface having a first degree of porosity, and the inner surface having a second degree of porosity less than the first degree of porosity, the first degree of porosity promoting internal tissue growth into the outer surface, and the second degree of porosity inhibiting internal tissue growth into the inner surface, and reducing the fluid pressure by transporting the fluid through the compatible material from a high-pressure position to a low-pressure position of the eye.

[0104] In another example ("Example 97"), a method for reducing the fluid pressure of an intraocular fluid includes placing a suprachoroidally implantable device in the subconjunctival region of the eye, wherein the device has a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir of the device having an internal volume, the outer surface being less uniform than the inner surface when both the outer and inner surfaces are observed at a magnification selected from 50 to 1000 times, respectively, adjusting the internal volume of the internal reservoir in situ, and reducing the fluid pressure by transporting the fluid from a high-pressure position to a low-pressure position of the eye through the compatible material.

[0105] In another example ("Example 98"), a method for reducing the fluid pressure of an intraocular fluid includes placing an upper choroidal implantable device in the subconjunctival region of the eye, the device having a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir of the device having an internal volume, the compatible material having variable porosity ranging from a first porosity located near the outer surface to a second porosity located near the inner surface and smaller than the first porosity, the first porosity promoting internal tissue growth toward the outer surface and the second porosity inhibiting internal tissue growth toward the inner surface, adjusting the internal volume of the internal reservoir in situ, and reducing the fluid pressure by transporting the fluid through the compatible material from a high-pressure position to a low-pressure position in the eye.

[0106] In another example ("Example 99"), a method for reducing the fluid pressure of an intraocular fluid includes placing a suprachoroidal implantable device in the subconjunctival region of the eye, wherein the device has a body portion formed of a compatible material having an outer surface and an opposite inner surface defining an internal reservoir having an internal volume, the outer surface having a first degree of porosity and the inner surface having a second degree of porosity smaller than the first degree of porosity, the first degree of porosity promoting internal tissue growth into the outer surface and the second degree of porosity inhibiting internal tissue growth into the inner surface, adjusting the internal volume of the internal reservoir in situ, and reducing the fluid pressure by transporting the fluid through the compatible material from a high-pressure position to a low-pressure position in the eye.

[0107] In addition to any one of Examples 97–99, according to another example ("Example 100"), the method further comprises positioning the first end of a sealable conduit between the conjunctival tissue and at least one of the scleral tissue and the anterior chamber (AC) of the eye, wherein the sealable conduit has a second end opposite to the first end, and fluidly connecting the second end of the sealable conduit to an internal reservoir of the device, the sealable conduit facilitating the in-situ adjustment of the internal volume of the internal reservoir.

[0108] In addition to Example 100, according to another example ("Example 101"), arranging a first end of a sealable conduit further includes sealing the first end of the conduit to prevent fluid communication through it.

[0109] In addition to Example 101, according to another example ("Example 102"), positioning the first end of the sealable conduit in the eye's AC further includes fluidically coupling the AC and the first end of the conduit in response to the fluid pressure applied from the AC, thereby facilitating fluid communication from the inner surface to the outer surface.

[0110] In another example ("Example 103"), a method for reducing the fluid pressure of intraocular fluid includes placing a suprachoroidally implantable device in the subconjunctival portion of the eye, wherein the device has a body portion defining a closed end and an open end, the body portion further including a first surface and a second surface on the opposite side, the open end being fluidically coupled to the anterior chamber (AC) of the eye, the first surface being less uniform than the second surface when the first surface and the second surface are observed at a magnification selected from 50 to 1000 times, and reducing the fluid pressure by transporting fluid through the first surface and the second surface from a high-pressure position to a low-pressure position of the eye.

[0111] According to another example ("Example 104"), a method for reducing the fluid pressure of intraocular fluid includes placing a suprachoroidally implantable device in the subconjunctival region of the eye, wherein the device has a body portion defining a closed end and an open end, the body portion further including a first surface and a second surface on the opposite side, the body portion having variable porosity transitioning from a first porosity located near the first surface to a second porosity located near the second surface and smaller than the first porosity, the open end of the device being fluidically coupled to the anterior chamber (AC) of the eye, the first porosity promoting internal tissue growth into the first surface and the second porosity inhibiting internal tissue growth into the second surface, and reducing fluid pressure by transporting the fluid from a high-pressure position to a low-pressure position of the eye through the first surface and the second surface.

[0112] According to another example ("Example 105"), a method for reducing the fluid pressure of intraocular fluid includes placing a suprachoroidally implantable device in the subconjunctival region of the eye, wherein the device has a body portion defining a closed end and an open end, the body portion including a first surface and a second surface on the opposite side, the first surface having a first porosity, the second surface having a second porosity smaller than the first porosity, the open end of the device being fluidically coupled to the anterior chamber (AC) of the eye, the first porosity promoting internal tissue growth into the first surface, and the second porosity inhibiting internal tissue growth into the second surface, and reducing the fluid pressure by transporting the fluid from a high-pressure position to a low-pressure position of the eye through the first surface and the second surface.

[0113] In another example ("Example 106"), a suprachoroidal implantable device may include a body having an outer surface and an inner surface, the body being formed from a conformable material having a thickness that defines an internal growth portion that promotes internal tissue growth and a boundary portion that inhibits internal tissue growth, wherein the internal growth portion corresponds to the outer surface, the boundary portion defines an internal reservoir within the body, the internal growth portion is characterized by microporous surface features visible at a first magnification, and the boundary portion is characterized by the absence of microporous surface features visible at the first magnification.

[0114] In addition to Example 106, according to another example ("Example 107"), the first magnification is 50 times, sometimes 100 times, sometimes 500 times, or sometimes 1000 times.

[0115] In addition to Examples 106 or 107, according to another example ("Example 108"), the microporous surface features are defined by node and fibril microstructure or fibrous microstructure.

[0116] In addition to any one of Examples 106-108, according to another example ("Example 109"), the internal reservoir has a fixed internal volume.

[0117] In another example ("Example 110"), a suprachoroidally implantable device is a body having an outer surface and an inner surface, the body having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye, wherein the body is formed of a material having a thickness that defines an internal growth portion that promotes internal growth of tissue and a boundary portion that inhibits internal growth of tissue, the internal growth portion defining at least a portion of the outer surface, and the boundary portion defining at least a portion of the inner surface of the body, so that when examined at a first magnification, the portion of the outer surface defined by the internal growth portion appears less uniform than the portion of the inner surface defined by the boundary portion.

[0118] In addition to Example 110, according to another example ("Example 111"), the boundary portion also defines a part of the outer surface of the main body.

[0119] The above examples are merely illustrative and should not be construed as limiting or narrowing the scope of the inventive concept provided otherwise by this disclosure. Although several embodiments are disclosed, further embodiments will become apparent to those skilled in the art from the following detailed description, which illustrates and describes exemplary embodiments. Therefore, the drawings and detailed description should be construed as illustrative and not limiting in nature. [Brief explanation of the drawing]

[0120] Brief explanation of the drawing The accompanying drawings are included to provide a further understanding of embodiments of the present disclosure, are incorporated herein, constitute part thereof, illustrate examples, and help to illustrate the principles of the present disclosure together with the description.

[0121] [Figure 1] Figure 1 is a schematic cross-sectional view of an eye including a therapeutic device implanted to facilitate the treatment of intraocular hypertension according to an embodiment disclosed herein.

[0122] [Figure 2A]Figure 2A is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0123] [Figure 2B] Figure 2B is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0124] [Figure 2C] Figure 2C is a cross-sectional view of an eye including an implantable device of Figure 2A or 2B, implanted to facilitate a reduction in intraocular pressure (IOP) or intraocular fluid pressure, according to embodiments disclosed herein.

[0125] [Figure 3A] Figure 3A is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0126] [Figure 3B] Figure 3B is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0127] [Figure 3C] Figure 3C is a cross-sectional view of an eye including the implantable device of Figure 3A or 3B, implanted to facilitate the reduction of intraocular IOP, according to an embodiment disclosed herein.

[0128] [Figure 3D] Figure 3D is a cross-sectional view of an eye including an implantable device of Figure 3A or 3B, implanted to facilitate a reduction in intraocular IOP, according to an embodiment disclosed herein.

[0129] [Figure 3E]Figure 3E is a cross-sectional view of an eye including an implantable device of Figure 3A or 3B, implanted to facilitate the reduction of intraocular IOP, according to an embodiment disclosed herein.

[0130] [Figure 4A] Figure 4A is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0131] [Figure 4B] Figure 4B is a schematic view of the front of the implantable device shown in Figure 4A, as seen from the direction indicated by line 4B-4B, according to an embodiment disclosed herein.

[0132] [Figure 4C] Figure 4C is a schematic cross-section of an implantable device according to an embodiment disclosed herein, cut along the line 4C-4C shown in Figure 4A.

[0133] [Figure 4D] Figure 4D is a cross-sectional view of an eye including an implantable device of Figure 4A, 4B, or 4C, implanted to facilitate the reduction of intraocular IOP, according to embodiments disclosed herein.

[0134] [Figure 4E] Figure 4E is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0135] [Figure 4F] Figure 4F is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0136] [Figure 5A] Figure 5A is a schematic cross-sectional view of an upper choroidal implantable device according to an embodiment disclosed herein.

[0137] [Figure 5B] Figure 5B is a schematic view of the front of the implantable device shown in Figure 5A, as seen from the direction indicated by line 5B-5B, according to an embodiment disclosed herein.

[0138] [Figure 5C] Figure 5C is a schematic cross-section of an implantable device according to an embodiment disclosed herein, when cut across the line 5C-5C shown in Figure 5A.

[0139] [Figure 5D] Figure 5D is a cross-sectional view of an eye including an implantable device of Figure 5A, 5B, or 5C, implanted to facilitate the reduction of intraocular IOP, according to embodiments disclosed herein.

[0140] [Figure 6] Figure 6 is a scanning electron microscope (SEM) image of a cross-section of the main body of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0141] [Figure 7A] Figure 7A is a 50x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image. [Figure 7B] Figure 7B is a 50x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0142] [Figure 8A] Figure 8A is a 100-fold magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image. [Figure 8B]Figure 8B is a 100-fold magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0143] [Figure 9A] Figure 9A is a 500x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image. [Figure 9B] Figure 9B is a 500x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0144] [Figure 10A] Figure 10A is a 1000x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image. [Figure 10B] Figure 10B is a 1000x magnified SEM image of the surface of the main body portion of an implantable device according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0145] [Figure 11] Figure 11 is a SEM image of the fibrous network microstructure on the outer surface of the main body portion of an implantable device according to an embodiment disclosed herein.

[0146] [Figure 12A] Figure 12A is a color-coded surface shape measurement image of the first surface or outer surface of a body portion according to an embodiment disclosed herein, and is shown to the scale included in the image.

[0147] [Figure 12B] Figure 12B is a monochrome surface shape measurement image of the surface shown in Figure 12A, and is shown to the same scale as included in the image.

[0148] [Figure 12C] Figure 12C is an angled, color-coded surface shape measurement image of the surface shown in Figure 12A, and is shown to the scale included in the image.

[0149] [Figure 12D] Figure 12D is the software legend window showing the surface properties shown in Figure 12A.

[0150] [Figure 13A] Figure 13A is a cross-sectional view of an egg-shaped implantable device according to an embodiment disclosed herein, before and after the application of a directional force as shown. [Figure 13B] Figure 13B is a cross-sectional view of an egg-shaped implantable device according to an embodiment disclosed herein, before and after the application of a directional force as shown.

[0151] [Figure 14A] Figure 14A is a cross-sectional view of an implantable device having a rounded rectangular shape before and after the application of a directional force as shown, according to an embodiment disclosed herein. [Figure 14B] Figure 14B is a cross-sectional view of an implantable device having a rounded rectangular shape before and after the application of a directional force as shown, according to an embodiment disclosed herein.

[0152] [Figure 15A] Figure 15A is a cross-sectional view of an egg-shaped, filled, implantable device according to an embodiment disclosed herein, before and after the application of a directional force as shown. [Figure 15B] Figure 15B is a cross-sectional view of an egg-shaped, filled, implantable device before and after applying a directional force as shown, according to an embodiment disclosed herein.

[0153] [Figure 16A] Figure 16A is a cross-sectional view of a filled, implantable device having a rounded rectangular shape, before and after the application of a directional force as shown, according to an embodiment disclosed herein. [Figure 16B] Figure 16B is a cross-sectional view of a filled, implantable device having a rounded rectangular shape, before and after the application of a directional force as shown, according to an embodiment disclosed herein.

[0154] [Figure 17] Figure 17 is a cross-sectional view of an eye including an implantable device of Figure 15A, 15B, 16A, or 16B, implanted to reduce intraocular IOP, according to embodiments disclosed herein.

[0155] Please understand that some reproductions of drawings and photographs may not necessarily be shown to the actual scale. In certain cases, details that are not necessary for understanding this disclosure, or details that would make it difficult to recognize other details, may be omitted. Of course, please understand that this disclosure is not necessarily limited to the specific examples or embodiments illustrated or depicted herein. [Modes for carrying out the invention]

[0156] Detailed explanation Definitions and Terms This disclosure is not intended to be confined to any extent. For example, terms used in this application should be interpreted broadly in the context of the meaning that a person skilled in the art would assign to such terms. A person skilled in the art will readily understand that various embodiments of the inventive concepts provided herein can be realized by any number of methods and apparatus configured to perform the intended function. Furthermore, the accompanying drawings referenced herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of this disclosure, and in this respect, the drawings should not be construed as limiting. However, some drawings depict anatomical structures and the arrangement of embodiments to such anatomical structures, and such representations should be understood as being accurately scaled and arranged, with some deviation being permissible as the size and position of depicted anatomical structures may vary from person to person.

[0157] With regard to terms relating to inaccuracy, the terms “about” and “approximately” may be used interchangeably to refer to measurements including the stated measurement and measurements that are reasonably close to the stated measurement. A measurement that is reasonably close to the stated measurement deviates by a reasonably small amount from the stated measurement to the extent that it can be understood and readily verified by a person skilled in the art in the relevant technology. Such deviations may result, for example, from measurement errors, differences in the calibration of measuring instruments and / or manufacturing equipment, human error in reading and / or setting of measurements, fine-tuning made to optimize performance and / or structural parameters to account for differences in measurements related to other components, specific implementation scenarios, improper adjustment and / or handling of an object by a person or machine, and / or similar. If it is determined that a person skilled in the art in the relevant technology cannot readily verify the value of such a reasonably small difference, the terms “about” and “approximately” shall be understood to mean plus or minus 10% of the stated value.

[0158] The phrases "at least one," "one or more," and "and / or" are open expressions that function as both conjunctions and separators. For example, expressions such as "at least one of A, B, and C," "at least one of A, B, or C," "one or more of A, B, and C," "one or more of A, B, or C," and "A, B, and / or C" mean A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C. In the above expressions, each of A, B, and C may be an element such as X, Y, and Z, or X1-X n Y1-Y m and Z1-Z o When referring to classes of elements such as X, Y, and Z, the phrase can refer to a single element selected from X, Y, and Z, a combination of elements selected from the same class (e.g., X1 and X2), and a combination of elements selected from two or more classes (e.g., Y1 and Z). o This refers to ( ).

[0159] When used herein, the terms or phrases “preventing internal growth of the organization” and “substantially inhibiting internal growth of the organization” include not only complete prevention but also minor and insignificant internal growth that does not substantially affect the performance of the device in the context described herein.

[0160] It should be understood that all maximum numerical limits shown throughout this disclosure are deemed to include all lower numerical limits as alternatives, as if such lower numerical limits were expressly specified herein. All minimum numerical limits shown throughout this disclosure are deemed to include all higher numerical limits as alternatives, as if such higher numerical limits were expressly specified herein. All numerical ranges shown throughout this disclosure are deemed to include all narrower numerical ranges that fall within such wider numerical ranges, as if such narrower numerical ranges were all expressly specified herein.

[0161] Before describing in detail any embodiment of this disclosure, it should be understood that this disclosure is not limited to the details of the arrangement of structures and components described in the following description or shown in the following drawings. Other embodiments of this disclosure are possible and can be implemented or performed in various ways. It should also be understood that the expressions and terms used herein are for illustrative purposes only and should not be considered limiting. The terms “includes,” “equipment,” “has,” and their variations herein are intended to encompass the items listed thereafter and their equivalents, as well as additional items.

[0162] As used herein, the term “fibril” refers to a long piece of material, such as a polymer, whose length and width are substantially different from each other. For example, a fibril may be similar to a string or fiber, and its width (or thickness) may be much shorter or smaller than its length. In some examples, the width or thickness of a fibril may be smaller (microscopic) than that of a fiber piece.

[0163] As used herein, the term “node” refers to a connection point between at least two fibrils, where connection can be defined as a place where two fibrils come into permanent or temporary contact with each other. In some examples, a node also refers to a polymer larger in volume than a fibril, where a fibril begins or ends at a node without a clear continuity of the same fibril. In some examples, a node is wider than a fibril but shorter in length.

[0164] As used herein, “node” and “fibril” are usually connected or interconnected, but not necessarily so, and can be used to represent, for example, objects having a microscopic size. A “microscopic” object can be defined as an object whose at least one dimension (width, length, or height) is substantially small, and whose object or details are not visible to the naked eye, or are difficult, if not impossible, to observe without the help of a microscope (including, but not limited to, a scanning electron microscope (SEM)) or any suitable type of magnifying device.

[0165] Description of various embodiments This disclosure relates to systems, devices, and methods for reducing intraocular pressure (IOP) or intraocular fluid pressure in a patient to treat glaucoma. In various embodiments, the therapeutic device or method is configured to treat ocular hypertension and / or glaucoma, for example, by reducing IOP from undesirable high levels that could lead to progressive and sometimes permanent loss of vision in the affected eye. In various embodiments, the suprachoroidal implantable device according to this disclosure is configured to promote internal tissue growth in the external surface of the implantable device or in the internal tissue growth portion in the thickness direction of the tissue. In some examples, the implantable device may be configured to deliver appropriate ophthalmic agents, including, but not limited to, therapeutic agents such as prostaglandin analogs (PGAs) (e.g., latanoprost), or other classes of therapeutic agents, including beta-blockers such as timolol, alpha-2 agonists such as brimonidine tartrate, carbonic anhydrase inhibitors such as dorzolamide, compounds of carbonic anhydrase inhibitors and beta-blockers, and compounds of alpha-agonists and beta-blockers that can be administered in combination with PGAs.

[0166] In some embodiments, such implantable devices are configured to have an internal volume that can be minimally invasively adjusted in situ one or more times without the need to remove the device from the implantation site, for example. Considering the size and target implantation sites in the subconjunctival and suprachoroidal regions, implantation can be performed outside the operating room where needle puncture and small incisions are commonly performed. Such adjustment of internal volume (e.g., increasing or decreasing the volume) can help to adequately relieve intraocular pressure, for example, if the initial volume of the implantable device is putting excessive pressure on the surrounding tissue.

[0167] Figure 1 shows an example of a method for implanting the suprachoroidal implantable device 100 disclosed herein into the subconjunctival and choroidal regions of the eye, such as between the sclera and choroid. The anterior chamber (AC), posterior chamber (PC), choroid, retina, lens, and vitreous humor (VB) associated with the implant are also shown.

[0168] Figures 2A and 2B show examples of suprachoroidal implantable devices 100 according to embodiments disclosed herein. The device 100 includes a body or body portion 200 formed from a compatible material. The body portion 200 has an outer surface 202, also called the internal growth portion of the body thickness, and an opposite inner surface 204, also called the boundary portion of the body thickness, the inner surface 204 defining an internal reservoir 206 of the body portion 200. The internal reservoir 206 may have a fixed volume before and after the implantation procedure, or it may have an adjustable internal volume such that the surgeon or practitioner can adjust the volume after the implantation of the device 100 by, for example, inserting a needle into the body portion 200 to remove some of the internal fluid, or by filling the reservoir 206 with additional fluid. In some examples, the body portion 200 is self-sealing, thereby sealing the puncture site immediately after the needle is withdrawn. In some examples, at certain magnifications, such as 100x, 200x, 500x, 1000x, or any appropriate magnification or range between them, the outer surface 202 is visually observed to be less uniform than the inner surface 204. This difference in appearance can be the result of differences or variations in microstructure, including porosity. For example, the main body portion 200 may have variable porosity, transitioning from a first porosity to a second porosity that is lower than the first porosity. The first porosity is located near the outer surface 202, and the second porosity is located near the inner surface 204. Thus, in some examples, the outer surface 202 may have a first porosity, and the inner surface 204 may have a second porosity, where the second porosity is smaller than the first porosity. The first porosity may promote internal tissue growth on the outer surface 202, while the second porosity may prevent or inhibit internal tissue growth through the inner surface 204. The main body 200 can be pre-sealed before the implant procedure in order to maintain the fixed volume of the reservoir 206.

[0169] In some cases, the ability of a surface to prevent or inhibit internal tissue growth on the surface of the main body, as described above, can be observed by scanning electron microscopy (SEM). In some cases, a bubble point test can be performed to test the ability to prevent or inhibit internal tissue growth. An example of such a bubble point test method is disclosed in ASTM Test Method F316-03 ("Standard Test Method for Pore Size Characteristics of Membrane Filters by Bubble Point Test and Mean Flow Test"). The bubble point test is based on the principle that a wetted liquid is held in these capillary pores by capillary attraction and surface tension, and the minimum pressure required to push the liquid out of these pores is a function of the pore diameter. The pressure at which a stable bubble flow appears in this test is the bubble point pressure. For example, Table 1 of the aforementioned ASTM Test Method F316-03 shows the general correlation between pore size and bubble point pressure for various fluids used. In some cases, pore sizes of less than approximately 1 μm may be able to prevent such internal tissue growth.

[0170] In Figure 2A, the main body portion 200 is manufactured from a single component, whereas in Figure 2B, the main body portion 200 is manufactured from two components 200A and 200B, which are bonded or joined at a location such as the peripheral edge 210 of the device 100. In some examples, the main body portion 200, as shown in Figure 2B, can be implemented as a single component. The main body portion 200 can be formed or manufactured by winding, coiling or folding a single component into a suitable shape, and then melting or sintering it, thereby reducing or eliminating seams in the main body portion 200 that occur when winding, coiling or folding a single component, for example. Also shown are filler materials 208 that can be contained or sealed within the reservoir 206 to maintain the internal volume of the device 100. In some examples, the main body portion 200 is partially pre-filled with filler material 208 to fill at least 10% of the maximum internal volume of the internal reservoir 206. In some examples, the filler material 208 may be pre-filled in an amount of approximately 10% to approximately 20%, approximately 20% to approximately 30%, approximately 30% to approximately 40%, approximately 40% to approximately 50%, approximately 50% to approximately 60%, approximately 60% to approximately 70%, approximately 70% to approximately 80%, or any suitable value / range between these, or a combination of these ranges, relative to the maximum capacity of the internal reservoir 206. For example, the filler material 208 may be any suitable fluid, such as a hydrogel, a saline solution, or any suitable drug, as further described herein, which may be selected to gradually pass through the compatible material from the inner surface 204 to the outer surface 202 over a period of 3, 5, 7, 10, 15, 20, 25, 30 days, or any suitable number of days or range between these, so that it is dispersed from the reservoir 206 into the surrounding intraocular environment, as desired. In some examples, the filler material 208 may be a flexible polymer material, including, but is not limited to, stretched polytetrafluoroethylene (ePTFE).In some examples, the filler material may include, but is not limited to, acrylamide, N-isopropylacrylamide, poly(methacrylic-grafted-ethylene glycol), cellulose, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (PEO-PPO-PEO) (also known as poloxamer or Pluronic®), or polyacrylate. In some examples, the filler material may be, but is not limited to, a biodegradable tissue filler containing collagen. In some examples, the filler material may be, but is not limited to, a biocompatible tissue filler containing a silicone gel and / or a biocompatible gel such as calcium hydroxyapatite gel.

[0171] Figure 2C shows how the device 100 of Figure 2A or 2B can be implanted according to the disclosed embodiment. The entire device 100 can be implanted subconjunctivally in the superior choroidal space within the eye, for example, the space between the sclera and choroid of the eye, more specifically the space below the sclera and above the choroid. In some examples, the implanted device 100 maintains its fixed volume and continues to apply a predetermined amount of outward pressure to surrounding tissues such as the sclera and / or choroidal tissue, thereby maintaining the space in an open configuration and allowing fluid to flow into the formed space. The fluid is aqueous humor, which under normal conditions flows freely through the AC and is drained through the intraocular drainage system, such as the trabecular meshwork. However, if a patient suffers from a condition that obstructs the ocular drainage system, the fluid can no longer flow freely, causing an increase in IOP. Thus, the space formed by the device 100 as shown in the figures is utilized as a secondary drainage pathway for fluid (aqueous humor) to flow out from the AC in order to reduce the intraocular IOP. Figures 3C, 3D, 3E, 4D, 5D and 17 similarly show the device 100 in various configurations as further disclosed herein, and by providing the space as described above, facilitate the formation of such a secondary drainage pathway for fluid and reduce the IOP. Possible directions of such fluid flow from the inside of the device 100 to the surrounding outside are indicated by arrows.

[0172] Figures 3A and 3B show examples of suprachoroidally implantable devices 100 according to various embodiments. In addition to the main body portion 200, surfaces 202 and 204, and reservoir 206 as described above, the device 100 further includes a sealable conduit 300 having a first end 302 and a second end 304 opposite the first end 302, the second end 304 being fluid-coupled to the internal reservoir 206 of the device 100, thereby facilitating the in-situ adjustment of the internal volume of the internal reservoir 206 by facilitating the inflow and outflow of fluid into and from the internal reservoir 206. The conduit 300 has a channel 306 that penetrates from the first end 302 to the second end 304 to facilitate such adjustment.

[0173] In Figure 3A, the conduit 300 is received (e.g., inserted) through the main body portion 200. In Figure 3B, the conduit 300 is sandwiched between two components 200A and 200B of the main body portion 200. In both cases, an adhesive component or other material is further placed between the outer surface of the conduit 300 and the main body portion 200 so that the conduit 300 can remain in place and not move from its position.

[0174] Figure 3C shows how the device 100 of Figure 3A or 3B can be implanted according to the disclosed embodiment. The main body portion 200 of the device 100 can be implanted subconjunctivally in the suprachoroidal space of the eye as shown, and the conduit 300 can be positioned to extend through the scleral tissue. The first end 302 of the conduit 300 can be left open to fluidly connect the AC and the first end of the conduit 300 when the device 100 is implanted, and can facilitate fluid communication from the inner surface 204 to the outer surface 202 in response to the fluid pressure applied from the AC. After the device 100 is implanted and the operator adjusts the internal volume of the device 100 in situ to restrict fluid communication through it, it is sealed as shown in Figure 3C to maintain the adjusted internal volume. This sealing can be done by any suitable means, including, but not limited to, closing at least the first end 302 of the conduit 300 by melting or sintering. As disclosed herein, the conduit 300 may be formed from any suitable material, such as a polymer having a predetermined melting point, to facilitate such means of sealing the first end 302. The possible directions of such fluid flow from inside the device 100 to the external environment and into the conduit 300 are indicated by arrows.

[0175] Figures 3D and 3E show a configuration in which the device 100 can be implanted such that the conduit 300 extends toward the AC rather than penetrating the scleral tissue. In Figure 3D, the first end 302 of the conduit 300 is sealed as described above, and the possible directions of such fluid flow from inside the device 100 to the external environment and into the conduit 300 are indicated by arrows. On the other hand, in Figure 3E, the first end 302 remains open, allowing fluid from the AC (e.g., aqueous humor) to flow from the first end 302 through the conduit 300 (or, more specifically, the channel 306 of the conduit 300). The fluid flow can be bidirectional, as indicated by the bidirectional arrows in Figure 3E. That is, the fluid can at any time flow into the conduit 300 from outside the device 100, or out of the device 100 from the reservoir 206 into the surrounding intraocular tissue. Therefore, device 100 can self-adjust its internal volume based at least partially on changes in the surrounding environment, more specifically, on changes in the fluid pressure surrounding device 100.

[0176] In some embodiments, one or more surfaces (e.g., a first surface or outer surface 202 and / or a second surface or inner surface 204) may include a microporous microstructure. For example, one or more surfaces may include a biocompatible material such as ePTFE. Furthermore, one or more surfaces may be formed from other biocompatible materials, including, but not limited to, polyurethane, silicone, polysulfone, polyvinylidene fluoride (PVDF), polyhexafluoropropylene (PHFP), perfluoroalkoxy polymer (PFA), polyolefin, fluorinated ethylene propylene (FEP), acrylic copolymer, and polytetrafluoroethylene (PTFE), which may be microporous or non-microporous.

[0177] One or more of the aforementioned surfaces may be in the form of one or more sheets or films and may include knitted, woven, and / or nonwoven fabric forms containing individual fibers or multiple fiber strands. In some embodiments, the surface may be formed from multiple sheets or films of polymer material. In some embodiments, the sheets or films may be mechanically bonded by lamination or other means to form the surface and to form the body portion of an implantable device such as the body portion 200. Bonding of the sheets or films may be achieved by a variety of mechanisms, including heat treatment, high-pressure compression, binders such as one or more adhesives, lamination, or other suitable methods known to those skilled in the art.

[0178] In some embodiments, adjacent surfaces (e.g., surfaces 202 and 204) and / or layers of material forming such surfaces may be partially or completely bonded or adhered by any of the following methods. For example, in some examples, the layers are joined by a thermal method in which each of the polymers forming the material is heated above its melting point. In some embodiments, such heat treatment promotes the formation of adhesion or cohesive bonds between the materials or material layers. In some embodiments, adjacent surfaces and / or layers of material forming such surfaces may be partially joined by a thermal method in which at least one material is heated above its melting point. Such heat treatment promotes the formation of adhesion or cohesive bonds between the materials or material layers. In some embodiments, one or more suitable adhesives are used to provide a well-bonded interface. Adjacent surfaces and / or layers of material forming such surfaces may be bonded to each other at one or more distinct locations, such as periphery (e.g., periphery 210), to form a stabilizing structure that extends throughout the resulting structure.

[0179] In some examples, the tube or conduit (e.g., a sealable conduit 300) and / or filling material 208 may include, but are not limited to, materials comprising PTFE, ePTFE, urethane, polyurethane, silicone (organopolysiloxane), polysulfone, PVDF, PHFP, PFA, polyolefin, FEP, ethylene fluorinated ethylene propylene (EFEP), ethylene tetrafluoroethylene (ETFE), 3'-(2-aminopyrimidyl)-2,2':5',2''-terthiophene (PATT) and acrylic copolymers. In some embodiments, the material may include other biocompatible polymers suitable for forming one or more tubes or conduits, and may include, but are not limited to, silicone-urethane copolymers, styrene / isobutylene copolymers, polyisobutylene, polyethylene-co-poly(vinyl acetate), polyester copolymers, nylon copolymers, fluorinated hydrocarbon polymers, and any of the aforementioned copolymers or mixtures. In various embodiments, elastomers or elastomer materials can include perfluoromethyl vinyl ether and tetrafluoroethylene, (per)fluoroalkyl vinyl ether (PAVE), copolymers of tetrafluoroethylene and perfluoromethyl vinyl ether, silicone, fluoroelastomers, urethane, butyl rubber, styrene-butadiene, isobutylene-isoprene, or TFE / PMVE copolymers.

[0180] In some examples, device 100 may include one or more portions configured to promote or allow cell invasion and / or tissue adhesion. The device may also deliver a drug that may include a single therapeutic agent (e.g., a pharmaceutical) or a drug that may include multiple therapeutic agents. The drug may include additional materials (e.g., bioabsorbable polymers, pharmaceutically acceptable carriers) to influence the elution of the therapeutic agent (e.g., bioabsorbable polymers) from the delivery device. Throughout this specification, a drug may be said to be a pharmaceutical, or a pharmaceutical composition or combination, as it may consist of both a therapeutic agent and / or additional materials for the effective elution of the therapeutic agent. For example, the drug may include bioabsorbable microparticles having sizes in the range of about 0.1 to 50 microns, about 1 to 50 microns, about 5 to 50 microns, about 15 to 50 microns, about 10 to 40 microns, about 15 to 25 microns, and about 18 to 23 microns. In some embodiments, the bioabsorbable microparticles have an average size of about 20 microns. In further embodiments, the therapeutic agent retained in the bioabsorbable microparticles may be latanoprost. The bioabsorbable microparticles are retained within the device 100 during use, while the drug is released from the bioabsorbable microparticles and therefore may be released from the device 100.

[0181] In some cases, the drugs may include, but are not limited to, anti-inflammatory agents typically used after surgery, such as dexamethasone, prednisolone, ketorolac, nepafenac, bromofenac, diclofenac, cyclosporine, or lifitegrast. In some cases, the drugs may include, but are not limited to, antibiotics typically used after surgery, such as moxifloxacin or gatifloxacin. In some cases, when a drug delivery system is configured to treat glaucoma, the API class may include latanoprost, bimatoprost, and prostaglandins such as latanoprost (e.g., XALATAN®). In certain cases, the API class may include beta-blockers such as timolol (e.g., Betimol®), alpha-agonists such as brimonidine or Alphagan®, carbonic anhydrase inhibitors such as dorzolamide or brinzolamide (e.g., Azopt®), or miotics such as pilocarpine. The API class may also include, but is not limited to, monoclonal antibodies such as bevacizumab (e.g., Avastin®), ranibizumab (e.g., Lucentis®), or aflibercept (e.g., Eylea®).

[0182] Figures 4A–4C show examples of suprachoroidal implantable devices 100 according to embodiments disclosed herein. The device 100 includes a body or body portion 400, which includes a closed end 406 and an open end 408 that is fluidly coupled to the AC of the eye when implanted. By example, the device 100 or its body 400 may have a substantially circular or round cross-section. The body portion 400 includes a first surface 402, also called the internal growth portion of the body thickness, and a second surface 404, also called the boundary portion of the body thickness, which may be similar in material, physical structure, or properties to the aforementioned outer surface 202 and inner surface 204, respectively. That is, in some examples, when observed at a particular magnification, such as 50x, 100x, 200x, 500x, 1000x, or any appropriate magnification value or range between them, the second surface 404 may be less uniform than the first surface 402. The main body portion 400 is pre-formed as a cup-shaped structure, that is, a substantially cylindrical structure, with the bottom closed to form a closed end 406 and the other end open to form an open end 408. In some examples, the main body portion 400 may have variable porosity, transitioning from a first porosity to a second porosity smaller than the first porosity. The first porosity is located near the first surface 402, and the second porosity is located near the second surface 404. In some examples, the first surface 402 has the first porosity, and the second surface 404 has the second porosity smaller than the first porosity. The first porosity can promote internal growth of tissue on the first surface 402, while the second porosity can prevent or inhibit internal growth of tissue through the second surface 404.

[0183] Figure 4D shows an example in which the device 100 of Figures 4A-4C is implanted such that the open end 408 of the main body portion 400 is in fluid communication with the AC, thereby facilitating unidirectional fluid flow, for example, from the AC to the internal volume of the device 100, and from the internal volume of the device 100 to the external environment, such as the suprachoroidal space. The main body portion 400 may be substantially cylindrical or tubular in shape or structure, and this substantially cylindrical or tubular structure can define the internal volume or internal space 414 of the main body portion 400. The internal volume or internal space 414 can be an open space, i.e., a volume not sealed from the surrounding environment. This structure can be self-supporting in order to maintain an open volume, whether its volume is empty or (partially or completely) filled with a fluid such as aqueous humor. The possible directions of such fluid flow from inside the device 100 to the external environment are indicated by arrows, and due to the pressure difference in the AC of the eye, there is little to no outflow through the open end 408. This unidirectional fluid flow can be facilitated when the intraocular pressure in the eye's AC is above a threshold pressure level (e.g., 20 mmHg, 30 mmHg, 40 mmHg, 50 mmHg, or any other appropriate value or range in between).

[0184] Figure 4E shows a schematic diagram of an example of device 100, where the closed end 406 of the main body portion 400 is formed by clamping and closing one end of a material originally formed as a tubular structure. After clamping one end of the tubular structure, the closed end 406 can be formed by melting or sintering the clamped end so that it remains permanently closed.

[0185] Figure 4F shows an example of a device 100 in which the main body portion 400 includes an external microporous layer 410 and an internal elastic support structure 412. The microporous layer 410 defines a first surface 402 and a second surface 404 as described above, and the support structure 412 is positioned within the microporous layer 410 and defines an internal volume or space 414. The support structure 412 may have a third porosity different from the first and second porosities as described above. For example, the third porosity may be greater than the first and second porosities, which can facilitate fluid communication between the internal volume or space 414 and the second surface 404. This allows fluid flowing into the internal volume or space 414 of the main body portion 400 to flow outward through the first surface 402 and into the surrounding environment. In some examples, the open end 408 receives fluid into the internal volume or space 414, and the closed end 406 allows the received fluid to flow outward and exit the internal volume or space 414. In some examples, the outer surface of the body portion 400 is defined by a first surface 402, and the inner surface of the body portion 400 is defined by a second surface 404.

[0186] Figures 5A to 5C show examples of suprachoroidal implantable devices 100 according to embodiments disclosed herein. The device 100 includes a body or body portion 400 formed from a material having a thickness that defines an internal growth portion that promotes internal tissue growth and a boundary portion that prevents or inhibits internal tissue growth. The internal growth portion defines at least a portion of the outer surface or external area of ​​the body 400 that is in direct contact with external tissue in the eye, and the boundary portion defines at least a portion of the inner surface or internal area of ​​the body 400. The boundary portion (or second surface 404) has two sections, namely, a first portion 404A that covers the entire inner surface of the body portion 400 and a second portion 404B that covers a portion of the outer surface of the body portion 400 up to, for example, the “threshold” labeled in Figure 5A. Therefore, a portion of the outer surface of the main body portion 400 may be covered or defined by the internal growth portion (or the first surface 402), and the remaining portion of the outer surface of the main body portion 400 may be covered or defined by the boundary portion (or the second section 404B of the second surface 404). The inner surface of the main body portion 400 is defined only by the boundary portion (or the first section 404A of the second surface 404). The second section 404B of the second surface 404 defines approximately 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or any other appropriate range or number in between the outer surface of the main body portion 400, and the remaining proportion of the outer surface is defined by the first surface 402. When inspected at first magnification, the portion of the outer surface defined by the internal growth portion (or the first surface 402) may appear less uniform than the portion of the inner surface defined by the boundary portion (or the second surface 404). The first magnification can be 50x, 100x in some cases, 500x in some cases, or 1000x in some cases.

[0187] Figure 5D shows an example of implanting the device 100 shown in Figures 5A-5C such that the second section 404B of the second surface 404 can extend into the AC. This ensures that only the portion of the outer surface of the device 100 defined by the first surface 402 is located within the suprachoroidal space, i.e., between the choroid and sclera. The first surface 402 promotes internal tissue growth from the scleral and choroidal tissues, while the second section 404B of the second surface 404 prevents or inhibits such internal tissue growth. The device 100 can facilitate unidirectional fluid flow from the AC to the internal volume of the device 100 and from the internal volume of the device 100 to the external environment (e.g., within the suprachoroidal space). Possible directions of fluid flow from the inside of the device 100 to the external environment are indicated by arrows, and due to the pressure difference within the AC of the eye, there is little to no outflow from the open end 408. Unidirectional fluid flow can be facilitated when intraocular pressure in the AC of the eye is above a threshold pressure level, such as 20 mmHg, 30 mmHg, 40 mmHg, 50 mmHg, or any other suitable value or range in between.

[0188] Figure 6 shows micrographs of microporous material of the main body portion 200 or 400 of the suprachoroidal implantable device 100 according to several embodiments. The bottom of Figure 6 is labeled "5.00kV 4.2mm x500 SE 1 / 23 / 2018," indicating that the distance between the two consecutive lines shown in the lower right corner is 10 μm. For example, the microporous material in Figure 6 may be referred to throughout this specification in relation to implantable devices or systems. As those skilled in the art will understand by referring to Figure 6, the microporous aspects and parameters of the microporous material can be defined in various ways. In the application of microporous materials in ophthalmic devices, such as the implantable device 100 described herein, which are configured to be placed in situ within eye tissue to control the internal fluid pressure of the eye, the microporous properties of such microporous materials can generally be characterized by a volumetric porosity value, which can be defined as the ratio of the volume of air or fluid contained within the microporous material to the total volume (or gross volume) of the microporous material.

[0189] In other definitions, volumetric porosity may be defined as the percentage of the volume of a microporous material occupied by non-structural or transient elements such as air or other fluids. For example, if the total volume is 100 mm². 3 And of those, 30mm 3 In the case of a microporous material containing chambers that hold air or fluid, the volumetric porosity is 0.3. This is because 30% of the volume of the microporous material is empty or a temporary space filled with air or other fluid.

[0190] To understand this, two microporous materials can have the same volumetric porosity, but the pore sizes presented to incoming or outgoing air or fluid can differ. For example, the first material may have a small number of large pores distributed over a certain total volume, while the second material may have a relatively large number of relatively small pores distributed over the same certain volume. If the air / fluid volume of the two materials is the same, both microporous materials can have the same volumetric porosity.

[0191] To further understand this, the properties of a microporous material used in a device can also be defined by the size of the passages through the microporous material, or similarly, by the pore size measured at the point where the passage terminates on the surface of the microporous material, or by the pore size measured along the length of the passage within the material. Microporous materials with small pores or passages may hinder flow within the material, while relatively large pores or passages may increase the passage of air or fluid into, out of, or within the microporous material.

[0192] To further understand this, the properties of microporous materials can also be defined by the degree of curvature of the passages through which fluids enter and pass. Relatively small or large passages can obstruct the fluid path due to the frequency of passage curvature or the placement of obstacles in the fluid path. The air / fluid passage rate of microporous materials can be controlled or defined by controlling or defining any of the above properties of the material, providing materials suitable for promoting intraocular pressure control for the treatment of diseases.

[0193] For brevity, the aforementioned properties and variables of the microporous materials used in the various embodiments and examples described herein can simply be expressed as porosity, which can be based on a criterion of volumetric porosity, pore or passage size, and / or flexibility. Referring again to Figure 6, the internal portion of the microporous material can have various porosities or void ratios (or volumetric porosity, pore size, and / or flexibility). The internal portion can extend between the inner surface 204 (or second surface 404) and the outer surface 202 (or first surface 402).

[0194] In either of these parts of the main body section 200 or 400, the porosity can range from relatively small pore size (SP), medium-small pore size (MSP), medium pore size (MP), medium-large pore size (MLP), and large pore size (LP), where LP is larger than MLP, MLP is larger than MP, MP is larger than MSP, and MSP is larger than SP. In some examples, the size of SP can range from approximately 0.01% to 2% of the size of LP, the size of MP can range from approximately 2% to 20% of the size of LP, and the size of MLP can range from approximately 20% to 80% of the size of LP. The size of SP can range from approximately 0.01 μm to approximately 1 μm in pore size (measured as pore diameter or average pore dimension). In some examples, pore diameter can be the maximum diameter measured across the pore or the maximum cross-sectional length of the pore, and average pore dimension can be the calculated average of different dimensional lengths measured across the pore. In some cases, as pore size increases from one category to the next (e.g., SP to MSP, or MSP to MP), porosity can increase by approximately 5 to 10 times. For the purposes of this discussion, assuming that the delivery passes through the microporous material along a relatively linear pathway, sequentially passing through the porosity of the inner surface 204 or second surface 404, the uniform internal portion, and the outer surface 202 or first surface 402, the combined flow resistance can be expressed by similarly linking each porosity. For example, the inner surface 204 or second surface 404 typically has low porosity throughout (e.g., to resist internal growth of tissue into the reservoir 206), while the internal portion and the outer surface 202 or first surface 402 portion may have porosity of any of the aforementioned degrees. Under these circumstances, for example, when the internal portion has moderate porosity and the outer surface 202 or first surface 402 has high porosity, the fluid is delivered from the reservoir 206 through the microporous material to, for example, the surrounding tissue of the device, and can be represented as SP-MP-LP. More examples are given below.

[0195] Various delivery channels can exist within a microporous material. Relatively linear channels can include, for example, the SP1-SP4-SP5 region or the SP3-MLP1-MP1-MSP1 region. While some channels are relatively linear, non-linear channels also exist. For example, under certain conditions, at least some flows can pass through regions where the resistance decreases, such as the SP1-LP1-LP2 region or the SP3-MLP1-LP1-LP2 region. As can be understood, the microstructure of a microporous material can undergo modification processes to obtain a specific type of flow passing through the microstructure. For example, the microstructure can have relatively uniform layers running transversely in layers within the microstructure, or it can have variable portions throughout the entire thickness of the microporous material, as shown here.

[0196] In some examples, the main body portion 200 or 400 defines the thickness of a wall portion extending between the inner surface 204 or second surface 404 (also called the boundary portion) and the outer surface 202 or first surface 402 (also called the internal growth portion). The thickness of the wall portion can define an intermediate portion or transitional portion 606 of the main body portion 200 or 400 located between the boundary portion and the internal growth portion, the transitional portion 606 having transitional porosity between the porosity of the low-porosity surface (e.g., having smaller pore sizes) of the inner surface 204 or second surface 404 (thickness boundary portion) and the porosity of the high-porosity surface (e.g., having larger pore sizes) of the outer surface 202 or first surface 402 (internal growth portion of the thickness structure). Additionally or alternatively, the transition portion 606 may have a transition portion porosity equal to the porosity of the low-porosity surface of the inner surface 204 or the second surface 404 and the porosity of the outer surface 202 or the first surface 402. Additionally or alternatively, the transition portion 606 may have a transition portion porosity equal to the porosity of the low-porosity surface of the inner surface 204 or the second surface 404. Additionally or alternatively, the transition portion 606 may have a transition portion porosity equal to the porosity of the high-porosity surface of the outer surface 202 or the first surface 402.

[0197] In some examples, the main body portions 200, 400 include a plurality of nodes 600 and fibrils 602. The nodes can be optionally present portions of the outer surface 202 or the first surface 402 and have a “clump” or larger volume of polymer than the fibrils. In some examples, the nodes include portions of the main body portions 200, 400 having a small pore size (SP), e.g., SP4 and SP5 enclosed in circles, as described above with respect to Figure 6. Thus, the main body portions 200, 400 are formed from a plurality of nodes and fibrils that are appropriately interconnected, intertwined, or interwoven with each other. In some examples, the nodes have different sizes and porosities, and the fibrils define spaces or openings 604 having a larger pore size (LP), thereby the pore size of the portions defined by the fibrils is larger than the pore size of the nodes. In some examples, the outer surface 202 or first surface 402 may have spaces or openings 604 (e.g., circles surrounding LP1 and LP2) formed between adjacent nodes 600 and defined by a plurality of fibrils 602. In some examples, the size of the openings or spaces 604 may be defined by the distance between adjacent nodes 600 (e.g., the internode distance). In some examples, the surface features of surfaces 202, 402 include solid portions (e.g., nodes 600 and fibrils 602, as well as other solid materials or objects defining the structure of the body portions 200, 400) and porous portions (e.g., internode regions defining the size of openings or spaces 604 that may be defined by solid materials or objects defining the structure of the body portions 200, 400). The porous portions may include pores uniformly dispersed between the solid portions, ranging in size from 5 μm to 100 μm. In some examples, the size of such pores can be approximately 1 μm to 5 μm, 5 μm to 10 μm, 10 μm to 15 μm, 15 μm to 20 μm, 20 μm to 30 μm, 30 μm to 40 μm, 40 μm to 50 μm, 50 μm to 60 μm, 60 μm to 70 μm, 70 μm to 80 μm, 80 μm to 90 μm, 90 μm to 100 μm, or any other suitable value / range between them, or a combination of those ranges.In some cases, the pore portions are flexible (for example, the solid portions are made of flexible material), and the pores can be expanded, so that the size of the pores can change, for example, under physiological conditions.

[0198] Figures 7A and 7B show a comparison of SEM images of surfaces taken at the same 50x magnification. The bottom of Figure 7A is labeled "5.00kV 15.4mm x50 SE 4 / 20 / 2023," and the distance between the two consecutive lines shown in the lower right corner represents 0.1mm. The bottom of Figure 7B is labeled "10.0kV 4.2mm x50 SE 5 / 3 / 2023," and the distance between the two consecutive lines shown in the lower right corner represents 0.1mm. Figure 7A shows surfaces 202 and 402. Figure 7B shows surfaces 202 and 402. Figure 7B shows surfaces 204 and 404. Other possible magnifications may be 100x, 200x, 500x, 1000x, or any other suitable magnification value or range between them, as shown in additional figures described herein.

[0199] Figures 8A and 8B show a comparison of SEM images of surfaces taken at the same 100x magnification. At the bottom of Figure 8A, it is labeled "5.00kV 4.1mm x100 SE 4 / 20 / 2023," and the distance between the two consecutive lines shown in the lower right corner represents 50 μm. At the bottom of Figure 8B, it is labeled "5.00kV 4.1mm x100 SE 4 / 20 / 2023," and the distance between the two consecutive lines shown in the lower right corner represents 50 μm. Figure 8A shows surfaces 202 and 402. Figure 8B shows surfaces 204 and 404.

[0200] Figures 9A and 9B show a comparison of SEM images of surfaces taken at the same 500x magnification. Figure 9A is labeled "5.00kV 4.1mm x500 SE 4 / 20 / 2023", and the distance between the two consecutive lines shown in the lower right corner represents 10 μm. The bottom of Figure 9B is labeled "10.0kV 4.1mm x500 SE 4 / 20 / 2023", and the distance between the two consecutive lines shown in the lower right corner also represents 10 μm. Figure 9A shows surfaces 202 and 402. Figure 9B shows surfaces 204 and 404.

[0201] Figures 10A and 10B show a comparison of SEM images of surfaces taken at the same 1000x magnification. At the bottom of Figure 10A, it is labeled "5.00kV 4.1mm x1.00k SE 4 / 20 / 2023," and the distance between the two consecutive lines in the lower right corner represents 5 μm. At the bottom of Figure 10B, it is labeled "10.0kV 4.1mm x1.00k SE 4 / 20 / 2023," and the distance between the two consecutive lines in the lower right corner also represents 5 μm. Figure 10A shows surfaces 202 and 402. Figure 10B shows surfaces 204 and 404.

[0202] When each of the surfaces being compared is observed at the same magnification, at least one of the following surface features, hereafter referred to as "surface features," may be observed at at least one of the aforementioned magnifications. In some cases, such features are observed more frequently in the SEM images of the outer surface 202 or the first surface 402 (Figures 7A, 8A, 9A, and / or 10A) than in the inner surface 204 or the second surface 404 (Figures 7B, 8B, 9B, and / or 10B). In some cases, such features are observed only in the SEM images of surface 202 or 402, and are substantially absent or not visually observable on surface 204 or 404.

[0203] In some examples, surface features may include a series of adjacent pores and / or gaps, such as openings or spaces 604 formed on the surface. For example, the number of pores on surface 202 or 402 may be greater than the number on surface 204 or 404.

[0204] In some examples, surface features may include roughness defined by the surface texture and / or pore size. For example, the roughness (which may be the average roughness) of surface 202 or 402 may be greater than that of surface 204 or 404. The definition and determination of surface roughness will be explained in more detail with reference to Figures 12A-12D.

[0205] In some examples, surface features may have a difference in depth or maximum depth measured relative to the surface. For example, surface 202 or 402 may define a deeper depth from the surface to the body than surface 204 or 404. For example, the thickness or depth of surfaces 204, 404 may be about 10% or less, 20% or less, 30% or less, 40% or less, 50% or less, or any other appropriate value or range in between, relative to the thickness or depth of surfaces 202, 402. The difference in thickness or depth promotes internal growth of tissue into the deeper parts of the material, while the material having a relatively thin layer prevents further internal growth of tissue into the interior. The definition and determination of surface depth will be explained in more detail with reference to Figures 12A-12D.

[0206] The body 200 may be formed from a conforming material having a thickness that defines an internal growth portion, such as a first surface 402 that promotes internal growth of tissue, and a boundary portion, such as a second surface 404 that prevents or inhibits internal growth of tissue. The internal growth portion corresponds to the outer surface 202, and the boundary portion can define an internal reservoir 206 within the body 200, which may have a fixed internal volume. The internal growth portion may be characterized by microporous surface features visible at a first magnification, and the boundary portion may be characterized by the absence of microporous surface features visible at a first magnification. As described in relation to other embodiments, the first magnification can be 50x, optionally 100x, optionally 500x, optionally 1000x, or any range or value in between.

[0207] In some cases, surface features can be defined by multiple fibrils extending between multiple nodes, and the presence of multiple fibrils extending between nodes on the outer surface is visually recognizable at a given magnification. Examples include microstructures defined by multiple fibrils extending between multiple nodes (these microstructures are more visible on the outer surface than on the inner surface), or fibrous microstructures. For example, in the magnified views of Figures 9A and 9B, and Figures 10A and 10B, the presence of nodes 600 and fibrils 602 extending between them (and openings or spaces 604 defined by fibrils 602) is visually recognizable or observable in SEM images taken of surfaces 202 and 402 (Figures 9A and 10A). However, such nodes and fibrils are difficult to observe in SEM images of surfaces 204 and 404 (Figures 9B and 10B), or in some cases, impossible to observe. Therefore, when the two surfaces are observed at the same magnification, they can be distinguished by differences in their surface features. In the examples above, nodes and fibrils are observable at 500x and 1000x magnification, but it should be understood that in some cases, surface features can be observed at lower magnifications such as 50x and 100x.

[0208] In some examples, the surface features may include a plurality of fibers 1100 that form a microstructure defining the structure of the main body portion 200, as shown in Figure 11. In some examples, the fibers may be nonwovens such as spunbond, meltblown, direct-spun, solution-spun, gel-spun, or electro-spun materials. For example, the fibers may be spunbond polymers, including, but not limited to, spunbond PTFE and spunbond polypropylene. As defined herein, the fibers differ from fibrils in that they are generally arranged between two or more nodes that are generally formed on the main body portion 200, while the fibers may form structures / microstructures such as, for example, fiber matrices, fiber webs, fiber networks, or interconnected fiber microstructures. As shown in Figure 11, the fibers 1100 are interconnected, entangled, or woven together so that the fibers can adhere to or bond with other fibers, and the adhesion and / or weaving promote the structural support of the fibers. In some examples, the fibers 1100 are arranged in an overlapping manner and then pressurized together when some of the fibers are heated to their melting point, so that at least some of the fibers melt or deform and are at least partially bonded together, as shown in the figure. In some examples, the fibers 1100 can define a number of openings or spaces 604 between them, these openings or spaces are interstitial spaces within the structure and can be large enough to allow internal growth of tissue through surfaces 202, 402.

[0209] In some cases, surface features are fewer or minimal on surface 204 or 404 than on other surfaces 202 or 402, so that the surface features of surface 204 or 404 are less visually observable or perceptible at the aforementioned magnification compared to other surfaces 202 or 402. In some cases, at the aforementioned magnification, features are not observable at all or may not be present at all on surface 204 or 404 (e.g., features cannot be reliably identified visually). As an exemplary example, without limitation, surfaces 204, 404 shown in Figures 9B and 10B may lack fibrils 602 connecting the individual nodes 600 present or observable on surfaces 202, 402 in Figures 9A and 10A. As described herein, Figures 9A and 9B show a magnification of 500x, and Figures 10A and 10B show a magnification of 1000x.

[0210] Referring to the outer surface 202 or the first surface 402, the first porosity may be defined by the first average pore size. Such a surface may be called a tissue engagement surface. In some examples, the tissue engagement surface has porosity extending within the engagement surface to an engagement depth that allows external tissue to engage in order to fix or anchor the main body portion 200 or 400 to the suprachoroidal region of the eye where the device 100 is implanted. In some examples, engagement between the tissue engagement surface and external tissue is observable after 10, 30, 50, 100 days or more. In some examples, sufficient tissue engagement may be defined by the accumulation of enough cells (or a sufficient number of cells) to attach or fix the implantable device in place, or by the accumulation of enough cells (or a sufficient number of cells) to minimize migration of the implantable device from the implantation site. In some examples, engagement between the tissue engagement surface and external tissue prevents or inhibits migration of the device 100 from the suprachoroidal region. In some cases, internal growth of external tissue at the tissue engagement surface does not significantly obstruct the fluid flow through the main body portion 200 or 400. Referring to the inner surface 204 or the second surface 404, the second porosity may be defined by a second average pore size that is smaller than the first average pore size.

[0211] Figures 12A to 12C show different surface topographic measurement images of the outer surface 202 or the first surface 402. In Figures 12A and 12B, a line representing 50 μm is shown in the lower corner of each figure. In the color-coded surface topographic measurement image of Figure 12A, node 600 is shown in red, indicating the highest elevation. Fibril 602 is shown in yellow or green, indicating a lower elevation than node 600. On the other hand, space or opening 604 is shown in blue or black, indicating the lowest elevation (depression). As shown in the legend in the upper left corner of Figure 12C, the red area indicates a maximum elevation of 5.614 μm, the black area indicates a minimum elevation of less than approximately -6 μm, and the yellow area indicates an elevation of approximately 0 μm. As shown in the grid scale, the distance between two consecutive lines on the grid in Figure 12C is 20 μm. Please note that these depth and height values ​​may vary depending on the calibration method of the profiler. For example, as shown in the yellow areas of Figures 12A and 12C, the profiler is calibrated so that a height of 0 μm approximately corresponds to fibril 602, with areas lower than fibril 602 defined as space or aperture 604, and areas higher than fibril 602 defined as node 600. In Figure 12B, the monochrome image shows the "cliff" or edge of node 600 as it descends from the highest elevation point (such as the top surface of node 600) to a lower elevation point (such as fibril 602), and the darkest areas show the space or aperture 604 defined between the fibrils.

[0212] Figure 12D shows a pop-up window that can be generated using any suitable surface geometry software capable of calculating surface features and properties based on the generated geometry image. In the example shown, the image was generated using a 3D optical profiler (e.g., VK-X3000 series) or a 3D optical profiler (e.g., VR-6000 series) developed by Keyence Corporation (Osaka, Japan), but other suitable optical profilers can also be used. Analysis performed by the software shows that the maximum height (or elevation) of the outer surface 202 or first surface 402 is 5.614 μm, the minimum height (or depth) is -23.577 μm, and the difference is 29.191 μm, or approximately 30 μm.

[0213] Therefore, surface roughness can be defined by the difference between the maximum and minimum heights determined using such surface morphometry methods, where a larger difference results in greater roughness. For example, the surface roughness of surfaces 202 and 402 can be defined as a difference between the maximum and minimum heights of at least 10 μm, at least 15 μm, at least 20 μm, at least 25 μm, at least 30 μm, at least 35 μm, at least 40 μm, or any other suitable value within this range. In comparison, the surface roughness of surfaces 204 and 404 can be defined as a difference between the maximum and minimum heights of 10 μm or less, 7 μm or less, 5 μm or less, 4 μm or less, 3 μm or less, 2 μm or less, 1 μm or less, or any other suitable value within this range. In some examples, the total thickness of the main body portion 200 or 400 (i.e., the distance measured between the maximum height of the outer surface 202 or the first surface 402 and the maximum height of the inner surface 204 or the second surface 404) can be approximately 100 μm, approximately 120 μm, approximately 150 μm, approximately 170 μm, approximately 200 μm, or any other suitable value within this range. In some examples, the difference between the maximum and minimum heights can be defined as a percentage of the total thickness of the main body portions 200, 400. For example, surfaces 202, 402 can have a height difference of at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, or any other suitable value within this range, relative to the total thickness of the main body portions 200, 400. In comparison, surfaces 204 and 404 can have a height difference of 10% or less, 7% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, or any other appropriate value within these ranges, relative to the total thickness of the main body portions 200 and 400. The surface roughness of the outer surface 202 or the first surface 402 is greater than the surface roughness of the inner surface 204 or the second surface 404.

[0214] Furthermore, the surface depth can be defined as the maximum surface depth (or minimum height measured in Figure 12D). Surfaces 202 and 402 may have a maximum or minimum depth measured relative to fibril 602, as shown in Figures 12A and 12C. Here, fibril 602 generally occupies the center of the range and serves as the reference point for other features such as node 600 and space or opening 604. Thus, the maximum depth of surfaces 202 and 402 may be at least 10 μm, at least 15 μm, at least 20 μm, at least 25 μm, at least 30 μm, at least 35 μm, at least 40 μm, or any other suitable value within this range. In comparison, the maximum depth of surfaces 204 and 404 may be 10 μm or less, 7 μm or less, 5 μm or less, 4 μm or less, 3 μm or less, 2 μm or less, 1 μm or less, or any other suitable value within this range. Alternatively, the maximum depth of surfaces 202, 402 may be at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, or any other suitable value within this range, relative to the total thickness of body portions 200, 400. By comparison, the maximum depth of surfaces 204, 404 may be 10% or less, 7% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, or any other suitable value within this range, relative to the total thickness of body portions 200, 400. The maximum depth of the outer surface 202 or the first surface 402 is greater than the maximum depth of the inner surface 204 or the second surface 404.

[0215] Figures 13A and 13B, 14A and 14B, 15A and 15B, and 16A and 16B illustrate examples of device 100 according to various embodiments disclosed herein, and how the dimensions of device 100 can change or transition from a first configuration to a second configuration in response to one or more directional forces (e.g., forces indicated by black arrows with white "F"s). The directional or external force can be any force acting on device 100 from the surrounding environment in which device 100 may be placed, for example, a force from the tissue surrounding device 100 after device 100 has been implanted. The flexibility to respond to forces acting on device 100 allows device 100 to adapt to various environmental conditions after implantation, for example, improving user comfort. Figures 13A, 13B, 15A, and 15B show a device 100 having a substantially oval cross-section, while Figures 14A, 14B, 16A, and 16B show a device having a rounded rectangular cross-section.

[0216] In Figures 13A, 13B and 14A, 14B, the main body portion 400 includes an internal space 414 into which fluid flows from AC as described above, as indicated by the arrows in Figure 17. The fluid passes from AC through the device 100 and flows out of the device 100 at various locations toward the external environment, such as the suprachoroidal lumen. In some examples, the main body portion 400 may have open ends at both ends of the device 100. When no external force is acting, the main body portion 400 takes on a first configuration having a first height H1 and a first width W1, as shown in Figures 13A and 14A. The height is smaller than the width, which allows for the formation of a relatively flat cross-section. When an external force is acting as indicated by the arrows in Figures 13B and 14B, the main body portion 400 takes on a second configuration having a second height H2 and a second width W2. Here, H2<H1かつW2> It is W1.

[0217] In Figures 15A, 15B and 16A, 16B, the main body portion 400 includes a first portion 1500 into which fluid flows from AC and a second portion 1502, as indicated by the arrows in Figure 17. The second portion 1502 (which may also be called the internal portion) is located inside the main body portion 400, below the first portion 1500 (which may also be called the external portion). When no external force is acting, the main body portion 400 has a first height H1 and a first width W1, as shown in Figures 15A and 16A. When an external force is acting as indicated by the arrows in Figures 15B and 16B, the main body portion 400 has a second height H2 and a second width W2, where the second height is lower than the first height and the second width is greater than the first width.<H1かつW2> This is W1. In Figures 13A-13B, 14A-14B, 15A-15B, and 16A-16B, the main body portion 400 can reversibly transition between the first configuration (H1 and W1) and the second configuration (H2 and W2) depending on whether an external force (F) is applied to the main body portion 400 from the surrounding tissues, etc., at the implant site (for example, transitioning back and forth with minimal or no permanent or irreversible defects). This transition allows the device 100 to fill any extra space around it at the implant site, such as the superior choroidal space. The transition from the first configuration to the second configuration allows the main body 400 to exert an expanding force on its surroundings and widen.

[0218] In some examples, the first portion 1500 and the second portion 1502 have different porosities. For example, the second portion 1502 has a higher porosity than the first portion 1500, allowing fluid to easily enter the main body portion 400 through the second portion (or internal portion) 1502. In some examples, the first portion 1500 and the second portion 1502 are made from different materials or different components combined with each other. In some examples, the first portion 1500 and the second portion 1502 are made from a single or integrated piece of material that has been processed to form regions of different porosities. In some examples, there may be a transition portion between the first portion 1500 and the second portion 1502, resulting in a gradual change in porosity between the first portion 1500 and the second portion 1502. In this case, the transition portion may have one or more porosities that are greater than the porosity of the first portion 1500 and less than the porosity of the second portion 1502. Porosity can be measured using any suitable measurement method, including, but not limited to, calculating the average pore size, measuring the time it takes for a given amount of fluid (such as water) to pass through the part, and / or measuring the time it takes for a given amount of gas (such as air) to pass through the part at a given pressure.

[0219] The aforementioned configuration differs from the examples shown by Ianchulev T et al., such as CyPass®, iStent Supra®, MINIject®, and BioStent®. For example, CyPass® and iStent Supra® are considered rigid and incompatible, while BioStent® is manufactured using biological tissue such as decellularized scleral allograft tissue. As the biological tissue is absorbed into the tissue surrounding the device, the effect of maintaining the drainage pathway for aqueous humor from the anterior chamber of the eye may be lost over time. On the other hand, MINIject® is manufactured so that the size of the connections between pores is highly uniformly controlled throughout the entire volume of the device, resulting in a uniform internal pore size of 27 μm, as described in Griason et al. (2020) "A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration" BMC Biomedical Engineering. (2020) 2:10. doi: 10.1186 / s42490-020-00045-1 :PMID: 33073174; PMCID: PMC7556975. Advantageously, in some examples, the device 100 may have varying pore sizes or porosity throughout, which, as described above, can have the advantage of more effectively reducing IOP by providing multiple different discharge paths for the fluid to pass through the device 100.

[0220] Various methods for controlling intraocular fluid pressure can be considered using the suprachoroidal implantable device 100 disclosed herein. For example, the device 100 may be provided by a practitioner or surgeon and positioned in the subconjunctival region of the eye as shown in any of Figures 1, 2C, 3C-3E, 4D, 5D, or 17, suitable for configuration of the device 100 used in treatment. Intraocular fluid pressure is controlled using the device 100 by directing the fluid through the compatible material of the device 100. Various methods for reducing intraocular fluid pressure are also disclosed herein. For example, the device 100 may be positioned in the subconjunctival region of the eye as shown in any of Figures 1, 2C, 3C-3E, 4D, 5D, or 17, suitable for configuration of the device 100 used in treatment. Fluid pressure is reduced by transporting the fluid from high-pressure areas to low-pressure areas of the eye through the compatible material of the device 100. The high-pressure area is located at AC, and the low-pressure area may be located in the subconjunctival area or in the surrounding space or region near the site where the device 100 is placed. After the completion of the implant procedure, internal tissue growth occurs, and it is permissible for tissue to partially grow within the device 100 over a period of time after the implant procedure. Generally, as described above, the first porosity promotes internal tissue growth on the outer surface 202 or the first surface 402, while the second porosity prevents or substantially inhibits internal tissue growth through the inner surface 204 or the second surface 404.

[0221] Referring to Figures 2A to 2C, in some examples, the device 100 may have a fixed volume, while in some examples, the device 100 may have an adjustable internal volume, allowing the practitioner or surgeon to place the device 100 in the subconjunctival region of the eye and then adjust the internal volume of the internal reservoir 206 in situ in response to the placement of the device 100 in the subconjunctival region of the eye. This adjustment can be performed, for example, using a hypodermic needle. Other mechanisms for adjusting the internal volume (e.g., shape memory materials, chemical or electrochemical reactions, or other mechanisms) are also conceivable.

[0222] In some examples, the sealable conduit 300, as described in relation to Figures 3A-3E, can be provided by the practitioner or surgeon, with the second end 304 of the conduit 300 being fluidically coupled to the reservoir 206, while the first end 302 is positioned, for example, between the conjunctival and scleral tissues of the eye, or within the AC of the eye. In some examples, the practitioner or surgeon seals the first end 302 of the conduit 300, thereby obstructing fluid communication through it. The sealing of the first end 302 can be performed after the device 100 has been implanted in the intended location in the eye, as described above. In some examples, if the first end 302 is positioned within the AC of the eye, the practitioner or surgeon can fluidically couple the AC with the first end 302 of the conduit 300, thereby facilitating fluid communication from the inner surface 204 to the outer surface 202 in response to fluid pressure applied from the AC.

[0223] The device 100, described in relation to Figures 4A-4F and 5A-5D, can be provided by the practitioner or surgeon, and the device 100 may be positioned in the subconjunctival region of the eye such that the open end 408 of the device 100 is fluidly coupled to the AC of the eye. After the implantation procedure, the first surface 402 can promote internal tissue growth within it, and the second surface 404 can prevent or inhibit internal tissue growth through its interior. As described above, internal tissue growth may take any appropriate number of days after the implantation procedure.

[0224] As disclosed herein, various methods can be considered for manufacturing the suprachoroidal implantable device 100. For example, a suitable compatible material is provided, and a body portion 200 or 400 is formed using that compatible material. Thus, the body portion 200 or 400 has an outer surface 202 or first surface 402 and an inner surface 204 or second surface 404, as described above.

[0225] In some examples, such as the device 100 shown in Figures 2A and 2B, the main body portion 200 is formed from a conformable material and is provided with a filler material 208 to define an internal reservoir 206 having a fixed volume. In some examples, the main body portion 200 is formed from a conformable material such that the internal reservoir 206 has an internal volume that can be adjusted in the field. In such examples, such as the device 100 shown in Figures 3A and 3B, a sealable conduit 300 is provided such that a second end 304 is fluidly coupled to the internal reservoir 206, allowing for easy field adjustment to the internal volume of the internal reservoir 206.

[0226] In some examples, such as the device 100 shown in Figures 4A-4C, 4E, and 5A-5C, the manufacturing method or process may include winding a compatible material around a mandrel, followed by heat treatment of the compatible material to form a body portion 400 having a closed end 406 and an open end 408 that fluidly connects to the AC of the eye when implanted. After heat treatment, the body portion 400 has a first surface 402 and a second surface 404 according to any of the embodiments described above, the first surface 402 promoting internal tissue growth when the device 100 is implanted. For example, at a certain magnification, the first surface 402 may be less uniform than the second surface 404. In some examples, the body portion 400 may have variable porosity, transitioning from a first porosity located near the first surface 402 to a second porosity located near the second surface 404 and lower than the first porosity. In some examples, the first surface 402 has a first porosity to promote internal growth of tissue into / through the first surface 402 to a desired depth, and the second surface 404 has a second porosity that can prevent or substantially inhibit internal growth of tissue through the second surface 404.

[0227] Referring to Figure 4F, in some examples, the manufacturing method or process may include wrapping a secondary compatible material around the mandrel before wrapping a compatible material (or primary compatible material) around the mandrel, and the primary compatible material being wrapped around the secondary compatible material. Heat treatment may be applied to both compatible materials, and the resulting body portion 400 includes both an outer layer 410 (formed by the primary compatible material) and an internal elastic support structure 412 (formed by the secondary compatible material). Specifically, heat treatment of the compatible material forms an outer microporous layer 410 defining both the first surface 402 and the second surface 404 of the body portion 400, and heat treatment of the secondary compatible material forms an internal elastic support structure 412 located within the outer microporous layer 410. The internal elastic support structure 412 defines the internal space of the device 100, and the internal elastic support structure 412 has a third porosity that is higher than the first and second porosities, thereby facilitating fluid communication between the internal volume or space 414 and the second surface 404, as described above.

[0228] Various modifications and additions can be made to the exemplary embodiments described without departing from the scope of this disclosure. For example, while the embodiments described above refer to certain features, the scope of this disclosure also includes embodiments having different combinations of features, and embodiments that do not include all of the features described. Accordingly, the scope of this disclosure is intended to encompass all alternative forms, modifications and variations included in the claims, as well as all equivalent forms thereof.

Claims

1. An upper choroidal implantable device comprising a main body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the main body portion having a fixed volume, The main body portion has variable porosity that transitions from a first porosity located near the outer surface to a second porosity located near the inner surface and smaller than the first porosity. A device wherein the first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits internal tissue growth through the inner surface.

2. The device according to claim 1, wherein the first porosity is defined by a first average pore size, and the second porosity is defined by a second average pore size smaller than the first average pore size.

3. The device according to claim 1 or 2, wherein the outer surface is a tissue engagement surface, the tissue engagement surface has porosity extending to the engagement surface at an engagement depth in which external tissue engages to fix or anchor the main body portion to the suprachoroidal portion of the eye implanted with the device, and the porosity is selected so that it can be observed after 30 days that the external tissue is engaged with the engagement surface at the engagement depth.

4. The device according to any one of claims 1 to 3, wherein the internal reservoir includes a filling material sealed inside, the filling material includes a drug, and optionally includes a drug selected to pass from the inner surface to the outer surface of the compatible material over a period of 30 days.

5. An upper choroidal implantable device comprising a main body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the main body portion having a fixed volume, The outer surface has a first degree of porosity, and the inner surface has a second degree of porosity that is smaller than the first degree of porosity. A device wherein the first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits internal tissue growth through the inner surface.

6. The device according to claim 5, wherein the first porosity is defined by a first average pore size, and the second porosity is defined by a second average pore size smaller than the first average pore size.

7. The device according to claim 5 or 6, wherein the outer surface is a tissue engagement surface, the tissue engagement surface has porosity extending to the engagement surface at an engagement depth in which external tissue engages to fix or anchor the main body portion to the suprachoroidal portion of the eye implanted with the device, and the porosity is selected so that it can be observed after 30 days that the external tissue is engaged with the engagement surface at the engagement depth.

8. The device according to any one of claims 5 to 7, wherein the internal reservoir includes a filling material sealed inside, the filling material includes a drug, and optionally includes a drug selected to pass through the compatible material from the inner surface to the outer surface over a period of 30 days.

9. A suprachoroidal implantable device comprising a main body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the main body portion having an internal volume adjustable in situ, wherein the main body portion has variable porosity that transitions from a first porosity located near the outer surface to a second porosity located near the inner surface and smaller than the first porosity, A device wherein the first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits internal tissue growth through the inner surface.

10. A suprachoroidal implantable device comprising a main body portion formed from a compatible material having an outer surface and an inner surface defining an internal reservoir of the main body portion having an internal volume that can be adjusted in situ, The outer surface has a first degree of porosity, and the inner surface has a second degree of porosity that is smaller than the first degree of porosity. A device wherein the first porosity promotes internal tissue growth on the outer surface, and the second porosity inhibits internal tissue growth through the inner surface.

11. A suprachoroidal implantable device comprising a main body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye, The main body portion includes a first surface and a second surface, and the main body portion has variable porosity that transitions from a first porosity located near the first surface to a second porosity located near the second surface and smaller than the first porosity. A device wherein the first porosity promotes internal growth of tissue on the first surface, and the second porosity inhibits internal growth of tissue through the second surface.

12. The device according to claim 11, wherein the main body portion is a tube structure having a first end and a second end, the first end is closed to form a closed end of the main body portion, and the second end is held in an open configuration to form an open end of the main body portion.

13. The device according to claim 11 or 12, wherein the main body portion has a substantially circular cross-section.

14. The device according to claim 11 or 12, wherein the main body portion has a substantially oval or rounded rectangular cross-section.

15. The device according to claim 14, wherein, when no external force is acting, the main body portion has a first configuration having a first height and a first width, and in response to an external force applied to the main body portion, the main body portion has a second configuration having a second height and a second width, wherein the second height is smaller than the first height and the second width is larger than the first width.

16. The device according to claim 15, wherein the main body portion reversibly transitions between the first configuration and the second configuration depending on whether or not an external force is applied to the main body portion.

17. The main body portion is, Outer microporous layer, and, An internal elastic support structure is disposed within the aforementioned external microporous layer and defines the internal space. Includes, The device according to any one of claims 11 to 16, wherein the external microporous layer defines both the first surface and the second surface, and the internal elastic support structure has a third degree of porosity.

18. The device according to claim 17, wherein the third porosity is greater than the first porosity and the second porosity, thereby promoting fluid communication between the internal space and the second surface.

19. A suprachoroidal implantable device comprising a main body portion having a closed end and an open end that can fluidly connect to the anterior chamber (AC) of the eye, The main body portion includes a first surface and a second surface, the first surface having a first porosity, and the second surface having a second porosity smaller than the first porosity. A device wherein the first porosity promotes internal growth of tissue on the first surface, and the second porosity inhibits internal growth of tissue through the second surface.

20. The device according to claim 19, wherein the main body portion is a tubular structure having a first end and a second end, the first end is closed to form a closed end of the main body portion, and the second end is held in an open configuration to form an open end of the main body portion.

21. The device according to claim 19 or 20, wherein the main body portion has a substantially circular cross-section.

22. The device according to claim 19 or 20, wherein the main body portion has a substantially oval or rounded rectangular cross-section.

23. The device according to claim 22, wherein, when no external force is acting, the main body portion has a first configuration having a first height and a first width, and in response to an external force applied to the main body portion, the main body portion has a second configuration having a second height and a second width, wherein the second height is lower than the first height and the second width is greater than the first width.

24. The device according to claim 23, wherein the main body portion reversibly transitions between the first configuration and the second configuration depending on whether or not an external force is applied to the main body portion.

25. The main body portion is, Outer microporous layer, and, An internal elastic support structure is disposed within the aforementioned external microporous layer and defines the internal space. Includes, The device according to any one of claims 19 to 24, wherein the external microporous layer defines both the first surface and the second surface, and the internal elastic support structure has a third degree of porosity.

26. The device according to claim 25, wherein the third porosity is greater than the first porosity and the second porosity, thereby promoting fluid communication between the internal space and the second surface.

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