Patent Application
20240407946
The present disclosure relates generally to apparatuses and methods for treating ocular hypertension. More specifically, the disclosure relates to apparatuses and methods for treating hypertension within an eye via a suprachoroidal implant.
Aqueous humor is a fluid that fills the anterior chamber of the eye and contributes to an intraocular pressure (IOP) or fluid pressure inside the eye. Ocular hypertension is a condition in the eye where the intraocular pressure or fluid pressure inside the eye is elevated. Untreated ocular hypertension can lead to disease, including glaucoma, which can result in a gradual and permanent loss of vision in the afflicted eye. Glaucoma affects more than 3 million people in the United States and is a group of diseases that damages the eye's optic nerve which, if left untreated, can result in vision loss and blindness. Raised IOP is the only modifiable risk factor for glaucoma. Thus, treatment of glaucoma is focused on lowering IOP to reduce the risk of disease progression and vision loss.
Many attempts have been made to treat ocular hypertension, and glaucoma in particular. Such attempts include surgical procedures that involve implantation of drainage devices designed to lower the TOP of the afflicted eye, as well as medicament administration. The goal of these treatments is to improve quality of life and to preserve visual function through a reduction of the IOP. Such treatment procedures vary in their surgical risk, invasiveness and ultimately the effectiveness in lowering IOP.
For example, implantable stents such as the CyPass® stent (Alcon Inc.), the iStent Supra® stent (Glaukos Corp.), the MINIject® stent (iSTAR Medical), and the BioStent® (Iantrek, Inc.) are some of the types of minimally invasive ab-interno suprachoroidal stents that have been used in the past, as summarized in Ianchulev et al. (2024), “Biotissue stent for supraciliary outflow in open-angle glaucoma patients: surgical procedure and first clinical results of an aqueous drainage biostent.” British Journal of Ophthalmology. 2024 Jan. 29; 108 (2): 217-222. doi: 10.1136/bjo-2022-322536. PMID: 36593090; PMCID: PMC10850681 (hereinafter referred to as “Ianchulev et al.”). As explained in Ianchulev et al., the CyPass® and iStent Supra® stents are rigid, non-conforming, non-permeable, and non-hydrophilic, while the MINIject® stent and the BioStent® are porous, hydrophilic, and permeable.
Initial glaucoma treatments are generally focused on enhancing existing aqueous outflow pathways including both the conventional (trabecular) and unconventional (uveoscleral) pathways. As these treatments fail, or the patient's glaucoma becomes un-responsive to treatment, the glaucoma is termed refractive and glaucoma drainage implants are often used.
Disclosed herein are suprachoroidal implantable devices and methods of controlling fluid pressure within an eye. Advantages of such devices and methods include controlling tissue ingrowth with respect to the outer surface of the implantable devices. In some examples, the advantages include adjustability of the internal volume of the implantable device in situ such that the internal volume can be controlled without removing the device from the location of implant. In some examples, the devices and methods disclosed herein provide the benefit of minimizing or inhibiting the development of fibrosis in the tissue surrounding the implant, and inhibiting the ingrowth from surrounding tissue through the device, particularly through the internal surface of the device. In various examples, the reservoir or inner volume of the device remains free of tissue ingrowth. In some examples, the external surface allows for tissue ingrowth in order to anchor the device to the location in which it may be implanted and/or supporting the surrounding tissue. The devices can be flexible and cause little or no discomfort to the patient after implant. In various implementations, the devices are capable of exerting outward forces on the external tissue of the eye in a location in which the device is implanted. Such outward forces may help maintain a secondary drainage pathway for aqueous humor to flow from the anterior chamber of the eye. This maintained flow can, in turn, help reduce the intraocular pressure (IOP) within the eye when the primary drainage pathway is obstructed, for example.
According to one example (“Example 1”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with a fixed volume. The external surface has a surface feature that is minimally present on the internal surface when the external and internal surfaces are each viewed at a magnification selected from a range of 50× to 1000×. Or, in some related examples, the external surface is characterized by a surface feature that is minimally present on the internal surface, and further wherein the surface feature is less visible at the internal surface than the external surface, and optionally wherein the surface feature is visible on the external surface at a magnification of 50× and generally not visible on the internal surface at a magnification of 50×, and optionally wherein the surface feature is visible on the external surface at a magnification of 100× and generally not visible on the internal surface at a magnification of 100×, and optionally wherein the surface feature is visible on the external surface at a magnification of 500× and generally not visible on the internal surface at a magnification of 500×, and optionally wherein the surface feature is visible on the external surface at a magnification of 1000× and generally not visible on the internal surface at a magnification of 1000×.
According to another example (“Example 2”) further to Example 1, the surface feature of the external surface includes a plurality of solid portions and a plurality of pore portions. The pore portions include pores of 5 μm to 100 μm in size, the pores being evenly distributed between the solid portions.
According to another example (“Example 3”) further to Example 2, the pore portions are flexible such that the pore are expandable, for example under physiologic conditions.
According to another example (“Example 4”) further to Example 1, the surface feature includes a surface roughness, and the surface roughness of the external surface is greater than the surface roughness of the internal surface.
According to another example (“Example 5”) further to Example 1, the surface feature includes a maximum depth, and the maximum depth of the surface feature at the external surface is greater than the maximum depth of the surface feature at the internal surface.
According to another example (“Example 6”) further to Example 1, the surface feature is defined by a microstructure defined by a plurality of fibrils extending between a plurality of nodes, and further wherein the microstructure is more visible at the external surface than the internal surface.
According to another example (“Example 7”) further to Example 1, the body portion is formed of a material having a microstructure defined by a plurality of fibers.
According to another example (“Example 8”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with a fixed volume. The external surface has a plurality of openings of up to 100 μm in size that are visually unobservable in the internal surface at a magnification, such as a magnification selected from a range of from 50× to 1000×. Or, in some related examples, the external surface has a plurality of openings of up to 100 μm in size that are visually unobservable at 50×, and optionally 100×, and optionally 500×, and optionally 1000×.
According to another example (“Example 9”) further to Example 8, the openings are defined by a plurality of fibrils extending between a plurality of nodes.
According to another example (“Example 10”) further to Example 8, the openings are defined by a plurality of fibers.
According to another example (“Example 11”) further to Example 10, the plurality of fibers include spunbond polymers.
According to another example (“Example 12”) further to any one of Examples 1-11, the internal surface inhibits tissue ingrowth therethrough.
According to another example (“Example 13”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with a fixed volume. The body portion has a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface. The first porosity facilitates tissue ingrowth more than the second porosity. Optionally, the first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface.
According to another example (“Example 14”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with a fixed volume. The external surface has a first porosity and the internal surface having a second porosity less than the first porosity. The first porosity facilitates tissue ingrowth more than the second porosity. Optionally, the first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface.
According to another example (“Example 15”) further to Example 13 or 14, 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.
According to another example (“Example 16”) further to any one of Examples 1-15, the external surface is a tissue engagement surface.
According to another example (“Example 17”) further to Example 16, the tissue engagement surface has a porosity extending into the engagement surface at an engagement depth to which an external tissue engages in order to secure or anchor the body portion at a suprachoroidal location in an eye at which the device is implanted.
According to another example (“Example 18”) further to Example 17, the porosity is selected such that the external tissue is observable to engage the engagement surface at the engagement depth after 30 days.
According to another example (“Example 19”) further to Example 17 or 18, the engaging of the tissue engagement surface with the external tissue inhibits migration of the device from the suprachoroidal location.
According to another example (“Example 20”) further to any one of Examples 17-19, the ingrowth of the external tissue on the tissue engagement surface does not significantly inhibit fluid flow through the body portion.
According to another example (“Example 21”) further to any one of Examples 1-20, the body portion is pre-sealed to maintain the fixed volume of the internal reservoir.
According to another example (“Example 22”) further to any one of Examples 1-21, the compliant material includes expanded polytetrafluoroethylene (ePTFE).
According to another example (“Example 23”) further to any one of Examples 1-22, the internal reservoir includes a filler material encapsulated therein.
According to another example (“Example 24”) further to Example 23, the filler material includes ePTFE or hydrogel.
According to another example (“Example 25”) further to Example 23, the filler material includes a medicament, and optionally a medicament selected to pass through the compliant material from the internal surface to the external surface over a period of 30 days.
According to another example (“Example 26”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with an internal volume that is adjustable in situ. The external surface is less uniform than the internal surface when the external and internal surfaces are each viewed at a magnification, such as a magnification selected from a range of from 50× to 1000×. Or, in some related examples, when the external and internal surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the external surface can be observed as being less uniform than the internal surface.
According to another example (“Example 27”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with an internal volume that is adjustable in situ. The body portion has a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface. The first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface.
According to another example (“Example 28”), a suprachoroidal implantable device includes a body portion formed of a compliant material having an external surface and an internal surface defining an internal reservoir of the body portion with an internal volume that is adjustable in situ. The external surface has a first porosity and the internal surface having a second porosity less than the first porosity. The first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface.
According to another example (“Example 29”) further to Example 27 or 28, 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.
According to another example (“Example 30”) further to any one of Examples 26-29, the external surface is a tissue engagement surface.
According to another example (“Example 31”) further to Example 30, the tissue engagement surface has a porosity extending into the engagement surface at an engagement depth to which an external tissue engages in order to secure or anchor the body portion at a suprachoroidal location in an eye at which the device is implanted.
According to another example (“Example 32”) further to Example 31, the porosity is selected such that the external tissue is observable to engage the engagement surface at the engagement depth after 30 days.
According to another example (“Example 33”) further to Example 31 or 32, the engaging of the tissue engagement surface with the external tissue inhibits migration of the device from the suprachoroidal location under physiologic conditions.
According to another example (“Example 34”) further to any one of Examples 31-33, the ingrowth of the external tissue on the tissue engagement surface does not significantly inhibit fluid flow through the body portion.
According to another example (“Example 35”) further to any one of Examples 26-34, the body portion is pre-sealed prior to implanting of the device.
According to another example (“Example 36”) further to any one of Examples 26-35, the body portion comprises ePTFE.
According to another example (“Example 37”) further to any one of Examples 26-36, the body portion has a maximum internal capacity and is partially pre-filled to less than the internal maximum capacity to define the internal volume.
According to another example (“Example 38”) further to Example 37, the body portion is partially pre-filled with a filler material to fill at least 10% of a maximum capacity of the internal volume of the internal reservoir.
According to another example (“Example 39”) further to Example 38, the filler material includes ePTFE, hydrogel, or combinations thereof.
According to another example (“Example 40”) further to Example 38, the filler material includes a medicament, and optionally a medicament selected to, or that otherwise passes through the compliant material from the internal surface to the external surface over a period of 30 days.
According to another example (“Example 41”) further to any one of Examples 26-40, the device further includes a sealable conduit having a first end and a second end fluidly coupled with the internal reservoir to facilitate in situ adjustment to the internal volume of the internal reservoir.
According to another example (“Example 42”) further to Example 41, the body portion and the sealable conduit comprise ePTFE.
According to another example (“Example 43”) further to Example 41 or 42, the first end of the sealable conduit is disposable in a subconjunctival location of an eye, and the first end is sealable after the in situ adjustment of the internal volume.
According to another example (“Example 44”) further to Example 43, the subconjunctival location is located between a conjunctival tissue and a scleral tissue of the eye.
According to another example (“Example 45”) further to Example 41, the first end of the sealable conduit is disposable in an anterior chamber (AC) of an eye.
According to another example (“Example 46”) further to Example 45, the first end is sealable after the in situ adjustment of the internal volume.
According to another example (“Example 47”) further to Example 45, the first end of the sealable conduit remains open to facilitate the in situ adjustment of the internal volume of the internal reservoir.
According to another example (“Example 48”), a suprachoroidal implantable device includes a body portion having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an eye. The body portion includes a first surface and a second surface opposite the first surface, and that is less uniform than the first surface when the first and second surfaces are each viewed at a magnification, for example a magnification selected from a range of from 50× to 1000×. Or, in some related examples, when the first and second surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the second surface can be observed as being less uniform than the first surface.
According to another example (“Example 49”), a suprachoroidal implantable device includes a body portion having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an eye. The body portion includes a first surface and a second surface, the body portion having a variable porosity that transitions from a first porosity located proximate the first surface to a second porosity less than the first porosity and located proximate the second surface. The first porosity facilitates tissue ingrowth at the first surface and the second porosity inhibits tissue ingrowth through the second surface.
According to another example (“Example 50”), a suprachoroidal implantable device includes a body portion having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an 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 less than the first porosity. The first porosity facilitates tissue ingrowth at the first surface and the second porosity inhibits tissue ingrowth through the second surface.
According to another example (“Example 51”) further to Example 49 or 50, 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.
According to another example (“Example 52”) further to any one of Examples 48-51, the external surface is a tissue engagement surface.
According to another example (“Example 53”) further to Example 52, the tissue engagement surface has a porosity at a depth with which an external tissue engages in order to secure or anchor the body portion at a suprachoroidal location in an eye at which the device is implanted.
According to another example (“Example 54”) further to Example 53, the engaging of the tissue engagement surface with the external tissue is observable after 30 days.
According to another example (“Example 55”) further to Example 53 or 54, the engaging of the tissue engagement surface with the external tissue inhibits migration of the device from the suprachoroidal location.
According to another example (“Example 56”) further to any of Examples 53-55, the ingrowth of the external tissue on the tissue engagement surface does not significantly inhibit fluid flow through the body portion.
According to another example (“Example 57”) further to any of Examples 48-56, the body portion comprises ePTFE.
According to another example (“Example 58”) further to any of Examples 48-57, the body portion is substantially hollow.
According to another example (“Example 59”) further to any of Examples 48-58, the body portion facilitates fluid communication therethrough from the second surface to the first surface in response to a fluid pressure applied from the AC.
According to another example (“Example 60”) further to Example 59, fluid from the AC is dispersible via the first surface to an external location within the eye.
According to another example (“Example 61”) further to Example 60, the external location is between a conjunctival tissue and a scleral tissue of the eye.
According to another example (“Example 62”) further to any of Examples 48-61, the body portion is a tubular construct having a first end and a second end, wherein the first end is closed to form the closed end of the body portion and the second end is retained in an open configuration to form the open end of the body portion.
According to another example (“Example 63”) further to Example 62, the first end is closed by pinching the first end of the tubular construct.
According to another example (“Example 64”) further to any of Examples 48-63, the body portion defines an internal region and an external region configured to directly contact an external tissue within an eye, the second surface covers an entirety of the internal region and a portion of the external region, and the first surface covers the remaining portion of the external region.
According to another example (“Example 65”) further to any one of Examples 48-64, the body portion has a substantially circular cross-section.
According to another example (“Example 66”) further to any one of Examples 48-64, the body portion has a substantially ovular or rounded rectangular cross-section.
According to another example (“Example 67”) further to Example 66, in an absence of external forces, the body portion assumes a first configuration that has a first height and a first width, and in response to the external forces being applied to the body portion, the body portion assumes a second configuration that has a second height and a second width, wherein the second height is less than the first height, and the second width is greater than the first width.
According to another example (“Example 68”) further to Example 67, the body portion reversibly transitions between the first configuration and the second configuration in the presence or absence of the external forces being applied to the body portion.
According to another example (“Example 69”) further to any of Examples 48-67, the 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 further wherein the internal elastic support structure has a third porosity.
According to another example (“Example 70”) further to Example 69, the third porosity is greater than the first porosity and the second porosity to facilitate fluid communication between the internal space and the second surface.
According to another example (“Example 71”), a method of controlling fluid pressure within an eye is disclosed. The method includes providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with a fixed volume and disposing the device in a subconjunctival location of the eye. The external surface is less uniform than the internal surface when the external and internal surfaces are each viewed at a magnification, for example a magnification selected from a range of from 50× to 1000×. Or, in some related examples, when the external and internal surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the external surface can be observed as being less uniform than the internal surface. The method also includes controlling fluid pressure in the eye by directing a fluid through the compliant material.
According to another example (“Example 72”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with a fixed volume, the body portion having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface; disposing the device in a subconjunctival location of the eye; and controlling fluid pressure in the eye by directing a fluid through the compliant material. The first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits, and optionally prevents, tissue ingrowth through the internal surface.
According to another example (“Example 73”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with a fixed volume, the external surface having a first porosity, the internal surface having a second porosity less than the first porosity; disposing the device in a subconjunctival location of the eye; and controlling fluid pressure in the eye by directing a fluid through the compliant material. The first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits, and optionally prevents, tissue ingrowth through the internal surface.
According to another example (“Example 74”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with an internal volume; disposing the device in a subconjunctival location of the eye, wherein the external surface is less uniform than the internal surface when the external and internal surfaces are each viewed at a magnification selected from a range of 50× to 1000× (or, in some related examples, when the external and internal surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the external surface can be observed as being less uniform than the internal surface); adjusting in situ the internal volume of the internal reservoir; and controlling fluid pressure in the eye by directing a fluid through the compliant material.
According to another example (“Example 75”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with an internal volume, the body portion having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface; disposing the device in a subconjunctival location of the eye, wherein the first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface; adjusting in situ the internal volume of the internal reservoir; and controlling fluid pressure in the eye by directing a fluid through the compliant material.
According to another example (“Example 76”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion formed of a compliant material and having an external surface and an opposing internal surface defining an internal reservoir with an internal volume, the external surface having a first porosity, the internal surface having a second porosity less than the first porosity; disposing the device in a subconjunctival location of the eye, wherein the first porosity facilitates tissue ingrowth at the external surface and the second porosity inhibits tissue ingrowth through the internal surface; adjusting in situ the internal volume of the internal reservoir; and controlling fluid pressure in the eye by directing a fluid through the compliant material.
According to another example (“Example 77”) further to any one of Examples 74-76, the method further includes: providing a sealable conduit having a first end and a second end; fluidly coupling the second end of the sealable conduit with the internal reservoir of the device, wherein the sealable conduit facilitates the adjusting in situ of the internal volume of the internal reservoir; and disposing the first end of the sealable conduit between a conjunctival tissue and a scleral tissue of the eye or in an anterior chamber (AC) of the eye.
According to another example (“Example 78”) further to Example 77, the disposing the first end of the sealable conduit between a conjunctival tissue and a scleral tissue of the eye or in an anterior chamber (AC) of the eye further includes: sealing the first end of the conduit to inhibit fluid communication therethrough.
According to another example (“Example 79”) further to Example 78, the disposing the first end of the sealable conduit in an AC of the eye further includes: fluidly coupling the AC and the first end of the conduit to facilitate fluid communication therethrough from the internal surface to the external surface in response to a fluid pressure applied from the AC.
According to another example (“Example 80”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion having a closed end and an open end, the body portion comprising a first surface and an opposing second surface; disposing the device in a subconjunctival location of the eye such that the open end of the device is fluidly coupled with an anterior chamber (AC) of the eye; and controlling fluid pressure in the eye by directing a fluid through the first and second surfaces. The first surface is less uniform than the second surface when the first and second surfaces are each viewed at a magnification selected from a range of 50× to 1000×. Or, in some related examples, when the first and second surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the first surface can be observed as being less uniform than the second surface.
According to another example (“Example 81”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion having a closed end and an open end, the body portion having a first surface and an opposing second surface, the body portion having a variable porosity that transitions from a first porosity located proximate the first surface to a second porosity less than the first porosity and located proximate the second surface; disposing the device in a subconjunctival location of the eye such that the open end of the device is fluidly coupled with an anterior chamber (AC) of the eye; and controlling fluid pressure in the eye by directing a fluid through the first and second porosities. The first porosity facilitates tissue ingrowth at the first surface and the second porosity inhibits tissue ingrowth through the second surface.
According to another example (“Example 82”), another method of controlling fluid pressure within an eye is disclosed. The method includes: providing a suprachoroidal implantable device having a body portion having a closed end and an open end, the body portion having a first surface and an opposing second surface, the first surface having a first porosity, and the second surface having a second porosity less than the first porosity; disposing the device in a subconjunctival location of the eye such that the open end of the device is fluidly coupled with an anterior chamber (AC) of the eye; and controlling fluid pressure in the eye by directing a fluid through the first and second porosities. The first porosity facilitates tissue ingrowth at the first surface and the second porosity inhibits, tissue ingrowth through the second surface.
According to another example (“Example 83”), a method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material; forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the external surface being less uniform than the internal surface at a magnification of from about 50× to about 1000× magnification to facilitate tissue ingrowth (or, in some related examples, when the external and internal surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the external surface can be observed as being less uniform than the internal surface); and providing the body portion with a filler material therein to define an internal reservoir with a fixed volume.
According to another example (“Example 84”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material; forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the body portion having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface; and providing the body portion with a filler material therein to define an internal reservoir with a fixed volume.
According to another example (“Example 85”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material with a first porosity on a first surface and a second porosity that is less than the first porosity on a second surface; forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the external surface having the first porosity to facilitate tissue ingrowth at the external surface, and the internal surface having the second porosity to inhibit tissue ingrowth through the internal surface; and providing the body portion with a filler material therein to define an internal reservoir with a fixed volume.
According to another example (“Example 86”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material; and forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the external surface being less uniform than the internal surface at a magnification of from about 50× to about 1000× magnification to facilitate tissue ingrowth (or, in some related examples, when the external and internal surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the external surface can be observed as being less uniform than the internal surface), wherein the internal surface defines an internal reservoir with an internal volume that is adjustable in situ.
According to another example (“Example 87”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material with a first porosity on a first surface and a second porosity that is less than the first porosity on a second surface; and forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the body portion having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface, wherein the internal surface defines an internal reservoir with an internal volume that is adjustable in situ.
According to another example (“Example 88”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: providing a compliant material with a first porosity on a first surface and a second porosity that is less than the first porosity on a second surface; and forming a body portion using the compliant material such that the body portion comprises an external surface and an internal surface, the external surface having the first porosity that facilitates tissue ingrowth at the external surface, and the internal surface having the second porosity that inhibits tissue ingrowth through the internal surface, wherein the internal surface defines an internal reservoir with an internal volume that is adjustable in situ.
According to another example (“Example 89”) further to any one of Examples 86-88, the method further includes: providing a sealable conduit having a first end and a second end fluidly coupled with the internal reservoir to facilitate in situ adjustment to the internal volume of the internal reservoir.
According to another example (“Example 90”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: wrapping around a mandrel a compliant material; and applying heat treatment to the compliant material to form a body portion having a closed end and an open end configured to be fluidly coupled with an anterior chamber (AC) of an eye, the body portion comprising a first surface and a second surface, the first surface being less uniform than the second surface at a magnification of from about 50× to about 1000× magnification to facilitate tissue ingrowth. Or, in some related examples, when the first and second surfaces are each viewed at a magnification of 50×, and optionally 100×, and optionally 500×, and optionally 1000×, the first surface can be observed as being less uniform than the second surface.
According to another example (“Example 91”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: wrapping around a mandrel a compliant material; and applying heat treatment to the compliant material to form a body portion having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an eye, the body portion comprising a first surface and a second surface, the body portion comprising a first surface and a second surface, the body portion having a variable porosity that transitions from a first porosity located proximate the first surface to a second porosity less than the first porosity and located proximate the second surface, the first surface having the first porosity to facilitate tissue ingrowth at the first surface of the body portion, and the second surface having the second porosity to inhibit tissue ingrowth through the second surface of the body portion.
According to another example (“Example 92”), another method of manufacturing a suprachoroidal implantable device is disclosed. The method includes: wrapping around a mandrel a compliant material with a first porosity on a first surface and a second porosity that is less than the first porosity on a second surface; and applying heat treatment to the compliant material to form a body portion having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an eye, the body portion comprising a first surface and a second surface, the first surface having the first porosity to facilitate tissue ingrowth at the first surface of the body portion, and the second surface having the second porosity to inhibit tissue ingrowth through the second surface of the body portion.
According to another example (“Example 93”) further to any one of Examples 90-92, the method further includes: prior to wrapping a compliant material around a mandrel, wrapping around the mandrel a secondary compliant material. Wrapping a compliant material around a mandrel includes wrapping the compliant material around the secondary compliant material. Furthermore, applying the heat treatment to the compliant material includes: applying the heat treatment to the compliant material to form an external microporous layer, wherein the external microporous layer defines both the first surface and the second surface of the body portion; and applying the heat treatment to the secondary compliant material to form an internal elastic support structure disposed within the external microporous layer and defining an internal space, wherein the internal elastic support structure has a third porosity greater than the first porosity and the second porosity to facilitate fluid communication between the internal space and the second surface.
According to another example (“Example 94”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir of the device having a fixed volume, wherein the external surface is less uniform than the internal surface when both the external and internal surfaces are each viewed at a magnification selected from a range of 50× to 1000×; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 95”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir of the device having a fixed volume, the compliant material having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface, wherein the first porosity facilitates tissue ingrowth into the external surface and the second porosity inhibits tissue ingrowth into the internal surface; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 96”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir of the device having a fixed volume, the external surface having a first porosity and the internal surface having a second porosity less than the first porosity, wherein the first porosity facilitates tissue ingrowth into the external surface and the second porosity inhibits tissue ingrowth into the internal surface; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 97”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir of the device having an internal volume, wherein the external surface is less uniform than the internal surface when both the external and internal surfaces are each viewed at a magnification selected from a range of 50× to 1000×; adjusting in situ the internal volume of the internal reservoir; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 98”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir of the device having an internal volume, the compliant material having a variable porosity that transitions from a first porosity located proximate the external surface to a second porosity less than the first porosity and located proximate the internal surface, wherein the first porosity facilitates tissue ingrowth into the external surface and the second porosity inhibits tissue ingrowth into the internal surface; adjusting in situ the internal volume of the internal reservoir; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 99”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion formed of a compliant material with an external surface and an opposing internal surface defining an internal reservoir with an internal volume, the external surface having a first porosity and the internal surface having a second porosity less than the first porosity, wherein the first porosity facilitates tissue ingrowth into the external surface and the second porosity inhibits tissue ingrowth into the internal surface; adjusting in situ the internal volume of the internal reservoir; and reducing the fluid pressure by conveying the fluid though the compliant material from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 100”) further to any one of Examples 97-99, the method further includes: disposing a first end of a sealable conduit between a conjunctival tissue and at least one of scleral tissue of the eye and an anterior chamber (AC) of the eye, the sealable conduit having a second end opposing the first end; and fluidly coupling the second end of the sealable conduit with the internal reservoir of the device, wherein the sealable conduit facilitates the adjusting in situ of the internal volume of the internal reservoir.
According to another example (“Example 101”) further to Example 100, the disposing of the first end of the sealable conduit further includes sealing the first end of the conduit to inhibit fluid communication therethrough.
According to another example (“Example 102”) further to Example 101, the disposing the first end of the sealable conduit in an AC of the eye further includes fluidly coupling the AC and the first end of the conduit to facilitate fluid communication therethrough from the internal surface to the external surface in response to a fluid pressure applied from the AC.
According to another example (“Example 103”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion defining a closed end and an open end, the body portion further comprising a first surface and an opposing second surface, wherein the open end is fluidly coupled with an anterior chamber (AC) of the eye, and wherein the first surface is less uniform than the second surface when the first and second surfaces are each viewed at a magnification selected from a range of 50× to 1000×; and reducing the fluid pressure by conveying the fluid though the first and second surfaces from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 104”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion defining a closed end and an open end, the body portion further comprising a first surface and an opposing second surface, the body portion having a variable porosity that transitions from a first porosity located proximate the first surface to a second porosity less than the first porosity and located proximate the second surface, wherein the open end of the device is fluidly coupled with an anterior chamber (AC) of the eye, and wherein the first porosity facilitates tissue ingrowth into the first surface and the second porosity inhibits tissue ingrowth into the second surface; and reducing the fluid pressure by conveying the fluid though the first and second surfaces from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 105”), a method of reducing a fluid pressure of a fluid within an eye includes: disposing a suprachoroidal implantable device in a subconjunctival location of the eye, the device having a body portion defining a closed end and an open end, the body portion further comprising a first surface and an opposing second surface, the first surface having a first porosity and the second surface having a second porosity less than the first porosity, wherein the open end of the device is fluidly coupled with an anterior chamber (AC) of the eye, and wherein the first porosity facilitates tissue ingrowth into the first surface and the second porosity inhibits tissue ingrowth into the second surface; and reducing the fluid pressure by conveying the fluid though the first and second surfaces from a high-pressure location of the eye to a low-pressure location.
According to another example (“Example 106”), a suprachoroidal implantable device may include a body having an external surface and an internal surface, the body being formed of a compliant material having a thickness defining an ingrowth portion that facilitates tissue ingrowth and a boundary portion that inhibits tissue ingrowth, the ingrowth portion corresponding to the external surface and the boundary portion defining an internal reservoir within the body, the ingrowth portion being characterized by visible microporous surface features at a first magnification and the boundary portion being characterized by an absence of visible microporous surface features at the first magnification.
According to another example (“Example 107”) further to Example 106, the first magnification is 50×, optionally 100×, optionally 500×, or optionally 1000×.
According to another example (“Example 108”) further to Example 106 or 107, the microporous surface features are defined by a node-and-fibril microstructure or a fiber microstructure.
According to another example (“Example 109”) further to any one of Examples 106-108, the internal reservoir has a fixed internal volume.
According to another example (“Example 110”), a suprachoroidal implantable device includes a body having a closed end and an open end fluidly couplable with an anterior chamber (AC) of an eye, a body having an external surface and an internal surface, the body being formed of a material having a thickness defining an ingrowth portion that facilitates tissue ingrowth and a boundary portion that inhibits tissue ingrowth, the ingrowth portion defining at least a portion of the external surface and the boundary portion defining at least a portion of the internal surface of the body, such that the portion of the external surface defined by the ingrowth portion appears less uniform when inspected at a first magnification than the portion of the internal surface defined by the boundary portion.
According to another example (“Example 111”) further to Example 110, the boundary portion also defines a portion of the external surface of the body.
The foregoing Examples are just that, and should not be read to limit or otherwise narrow the scope of any of the inventive concepts otherwise provided by the instant disclosure. While multiple examples are disclosed, still other embodiments will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative examples. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature rather than restrictive in nature.
The accompanying drawings are included to provide a further understanding of the embodiments of the disclosure and are incorporated in and constitute a part of this specification, illustrate examples, and together with the description serve to explain the principles of the disclosure.
It should be understood that some of the drawings and replicas of the photographs may not necessarily be shown to scale. In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted. It should be understood, of course, that the disclosure is not necessarily limited to the particular examples or embodiments illustrated or depicted herein.
This disclosure is not meant to be read in a restrictive manner. For example, the terminology used in the application should be read broadly in the context of the meaning those in the field would attribute such terminology. Persons skilled in the art will readily appreciate that the various embodiments of the inventive concepts provided in the present disclosure can be realized by any number of methods and apparatuses configured to perform the intended functions. It should also be noted that the accompanying figures referred to herein are not necessarily drawn to scale, but may be exaggerated to illustrate various aspects of the present disclosure, and in that regard, the figures should not be construed as limiting. Some figures do, however, represent anatomy and the positioning of embodiments relative to that anatomy and such representations should be understood to be scaled and positioned accurately, with some deviation permitted as the anatomical structures depicted will vary in size and position from person to person.
With respect to terminology of inexactitude, the terms “about” and “approximately” may be used, interchangeably, to refer to a measurement that includes the stated measurement and that also includes any measurements that are reasonably close to the stated measurement. Measurements that are reasonably close to the stated measurement deviate from the stated measurement by a reasonably small amount as understood and readily ascertained by individuals having ordinary skill in the relevant arts. Such deviations may be attributable to measurement error, differences in measurement and/or manufacturing equipment calibration, human error in reading and/or setting measurements, minor adjustments made to optimize performance and/or structural parameters in view of differences in measurements associated with other components, particular implementation scenarios, imprecise adjustment and/or manipulation of objects by a person or machine, and/or the like, for example. In the event it is determined that individuals having ordinary skill in the relevant arts would not readily ascertain values for such reasonably small differences, the terms “about” and “approximately” can be understood to mean plus or minus 10% of the stated value.
The phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “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” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together. When each one of A, B, and C in the above expressions refers to an element, such as X, Y, and Z, or class of elements, such as X1-Xn, Y1-Ym, and Z1-Zo, the phrase is intended to 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) as well as a combination of elements selected from two or more classes (e.g., Y1 and Zo).
As used herein, the terms or phrases “prevent tissue ingrowth” and “substantially inhibit tissue ingrowth” or “substantially inhibit tissue ingrowth” are meant to be inclusive of not only complete prevention, but also minor, inconsequential ingrowth that does not substantially impact device performance in the context described.
It should be understood that every maximum numerical limitation given throughout this disclosure is deemed to include each and every lower numerical limitation as an alternative, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this disclosure is deemed to include each and every higher numerical limitation as an alternative, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this disclosure is deemed to include each and every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.
Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
The term “fibril” as used herein describes an elongated piece of material such as a polymer, where the length and width are substantially different from each other. For example, a fibril may resemble a piece of string or fiber, where the width (or thickness) is much shorter or smaller than the length. In some examples, a fibril may be smaller (microscopic) in width or thickness than a piece of fiber.
The term “node” as used herein describes a connection point of at least two fibrils, where the connection may be defined as a location where the two fibrils come into contact with each other, permanently or temporarily. In some examples, a node may also be used to describe a larger volume of polymer than a fibril and where a fibril originates or terminates with no clear continuation of the same fibril through the node. In some examples, a node has a greater width but a smaller length than the fibril.
As used herein, “nodes” and “fibrils” may be used to describe objects that are usually, but not necessarily, connected or interconnected, and have a microscopic size, for example. A “microscopic” object may be defined as an object with at least one dimension (width, length, or height) that is substantially small such that the object or the detail of the object is not visible to the naked eye or difficult, if not impossible, to observe without the aid of a microscope (including but not limited to a scanning electron microscope or SEM, for example) or any suitable type of magnification device.
The present disclosure relates to systems, devices, and methods for lowering an intraocular pressure (IOP) or fluid pressure within an eye of a patient to treat glaucoma. In various embodiments, the treatment device or method is configured to treat, for example, ocular hypertension and/or glaucoma, by causing the IOP to decrease from undesirably high levels that may lead to a gradual and sometimes permanent loss of vision in the afflicted eye. In various embodiments, the suprachoroidal implantable devices according to the instant disclosure are configured to facilitate tissue ingrowth at an external surface, or tissue ingrowth portion of the thickness, of the implantable devices. In some examples, the implantable devices may be configured to deliver suitable ocular medicaments including but not limited to therapeutic agents, such as prostaglandin analogs (PGAs) (e.g., latanoprost), or therapeutic agents from other medicament classes, including beta-blockers such as timolol, alpha-2-agonists such as brimonidine tartrate, or carbonic anhydrase inhibitors such as dorzolamide, compounds of carbonic anhydrase inhibitors and beta-blockers, and compounds of alpha-agonists and beta-blockers which may be administered in combination with PGAs, for example.
In some embodiments, such implantable devices are configured to be implanted and have an internal volume that is adjustable one or more times, for example minimally invasively in situ without requiring removal of the device from an implantation site. Given the size and the subconjunctival and suprachoroidal target implantation locations, implantation procedures can be performed outside of the operating room, where needle puncture and small incisions are commonly performed. Such adjustment to the internal volume (e.g., increase or decrease in the volume) may help release the pressure within the eye as suitable if the initial volume of the implantable device applies too much pressure to the surrounding tissue, for example.
In some examples, the ability for a surface to prevent or inhibit tissue ingrowth at a surface of the body portion as explained above may be observed via scanning electron microscopy (SEM). In some examples, a bubble point test may be performed to test the ability to prevent or inhibit tissue ingrowth. An example of such bubble point test method is disclosed in ASTM Testing Method F316-03 (“Standard Test Methods for Pore Size Characteristics of Membrane Filters by Bubble Point and Mean Flow Pore Test”). The bubble point test is based on the principle that a wetting liquid is held in these capillary pores by capillary attraction and surface tension, and the minimum pressure required to force liquid from these pores is a function of pore diameter. The pressure at which a steady stream of bubbles appears in this test is the bubble point pressure. For example, Table 1 of the aforementioned ASTM Testing Method F316-03 shows a general correlation between pore size and bubble point pressure with respect to the different fluids used. In some examples, a pore size of less than about 1 μm may be capable of preventing such tissue ingrowth.
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In some embodiments, one or more of the surfaces (e.g., the first or external surface 202 and/or the second or internal surface 204) may include a microporous microstructure. For example, one or more of the surfaces may include biocompatible materials such as ePTFE. Additionally, one or more of the surfaces may be formed of other biocompatible materials including biocompatible polymers, which may or may not be microporous, including, but not limited to, polyurethane, silicone, polysulfone, polyvinylidene fluorine (PVDF), polyhexafluoropropylene (PHFP), perfluoroalkoxy polymer (PFA), polyolefin, fluorinated ethylene propylene (FEP), acrylic copolymers, and polytetrafluoroethylene (PTFE).
One or more of the aforementioned surfaces may be in the form of one or more sheets or films, and they may include knitted, woven, and/or non-woven forms including individual or multi-fiber strands. In some embodiments, the surface(s) may be formed from a plurality of sheets or films of polymer material. In some embodiments, the sheets or films may be laminated or otherwise mechanically coupled together to form the surface(s) as well as to form the body portion of the implantable device, such as the body portion 200. Coupling of the sheets or films may be accomplished by a variety of mechanisms, including heat treatment, high pressure compression, bonding agents such as one or more adhesives, lamination, or other suitable methods known to one of skill in the art.
In some embodiments, adjacently-situated surfaces (e.g., the surfaces 202 and 204) and/or the layers of material forming such surfaces, may be partially or completely bonded or adhered in any of a variety of manners. For example, in some examples the layers are bonded via thermal methods where each of the polymers forming the materials are brought to or above their melting temperatures. In some embodiments, such thermal processes facilitate adhesive or cohesive bond formation between the materials or layers of material. In some embodiments, adjacently situated surfaces and/or the layers of material forming such surfaces, may be partially bonded via thermal methods where at least one of the materials is brought to or above its melting temperature. Such thermal processes may facilitate adhesive or cohesive bond formation between the materials or layers of material. In some embodiments, one or more suitable adhesives are utilized and provide a sufficiently bonded interface. Adjacently situated surfaces and/or the layers of material forming such surfaces, may be coupled together at one or more discrete locations such as the periphery (e.g., periphery 210) to form stabilizing structures that extend through the resulting structure.
In some examples, the tube or conduit (e.g., the sealable conduit 300) and/or the filler material 208 may comprise material(s) including but not limited to: PTFE, ePTFE, urethanes, polyurethane, silicones (organopolysiloxanes), 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, among others. In some embodiments, the materials may include other biocompatible polymers suitable for use in forming any one or more of the tube or conduit including, but not limited to, copolymers of silicon-urethane, styrene/isobutylene copolymers, polyisobutylene, polyethylene-co-poly(vinyl acetate), polyester copolymers, nylon copolymers, fluorinated hydrocarbon polymers and copolymers or mixtures of any of the foregoing may be used. In various embodiments, the elastomer or elastomeric material may include perfluoromethyl vinyl ether and tetrafluoroethylene, (per) fluoroalkylvinylethers (PAVE), a copolymer of tetrafluoroethylene and perfluoromethyl vinyl ether, silicone, a fluoroelastomer, a urethane, butyl rubber, styrene-butadiene, isobutylene-isoprene, or a TFE/PMVE copolymer.
In some examples, the device 100 may include one or more portions that are configured to promote or permit cellular infiltration and/or tissue attachment. The device may also deliver medicament which may include a single therapeutic agent (e.g., a medication), or may include multiple therapeutic agents. The medicament may include additional materials (e.g., bioabsorbable polymers, pharmaceutically acceptable carrier) to affect the elution of the therapeutic agents (e.g., bioabsorbable polymers) from the delivery device. Throughout the description herein, the medicament may also be referred to as a drug or a pharmaceutical composition or combination as is may be composed of both a therapeutic agent and/or additional materials for effective elution of the therapeutic agent. For example, the medicament may include bioabsorbable microparticles having a size ranging between approximately 0.1 microns to 50 microns, or from approximately 1 micron to 50 microns, or from approximately 5 microns to 50 microns, or from approximately 15 microns to 50 microns, or from approximately 10 microns to 40 microns, or approximately from 15 microns to 25 microns, or approximately 18 microns to 23 microns. In some embodiments, the bioabsorbable microparticles have an average size of approximately 20 microns. In further embodiments, the therapeutic agent retained in the bioabsorbable microparticles may be latanoprost. The bioabsorbable microparticles may be retained within the device 100 during use, while the medicament may be released from the bioabsorbable microparticles, and as such, the device 100.
In some examples, the medicament may include anti-inflammatory medicaments which are typically used in post-operation, including but not limited to: dexamethasone, prednisolone, ketorolac, nepafenac, bromofenac, diclofenac, cyclosporine, or lifitegrast. In some examples, the medicament may include antibiotics typically used in post-operation, including but not limited to moxifloxacin or gatifloxacin. In some examples, when the medicament delivery system is so arranged to treat glaucoma, API classes can include prostaglandins such as latanoprost, bimatoprost, and latanoprost (e.g., XALATAN®). In certain instances, active pharmaceutical ingredient (API) classes can include beta blockers such as timolol (e.g., Betimol®); alpha agonist such as brimonidine or Alphagan®; or carbonic anhydrase inhibitors such as dorzolamide, brinzolamide (e.g., Azopt®); or miotics such as pilocarpine. API classes can include monoclonal antibodies including but not limited to: bevacizumab (e.g., Avastin®), ranibizumab (e.g., Lucentis®), or aflibercept (e.g., Eylea®).
In another definition, a volumetric porosity can be defined as a percentage of the microporous material volume that is occupied by non-structural or transient elements such as air or other fluids. For example, a microporous material with an overall volume of 100 mm3 and with 30 mm3 of that volume comprising chambers holding air or a fluid would have a volumetric porosity value of 0.3 because 30% of the volume of the microporous material is empty or transient space that is filled with air or other fluids.
As can be appreciated, two microporous materials can have the same volumetric porosity but differ in the pore sizes presented to the incoming or exiting air or fluid. For example, a first material can a have a small number of large pores distributed over a fixed overall volume and a second material can have a relatively large number of relatively smaller pores distributed over the same fixed volume, and both microporous materials could have the same volumetric porosity if the air/fluid volume of the two materials are the same.
As can be further appreciated, the properties of the microporous materials used in the device can also be defined by the size of the passages passing through the microporous material or similarly defined as a pore size measured where a passage terminates at a surface of the microporous material or measured along a length of a passage within the material. Microporous materials with small pores or passages can impede flow through the material and comparatively large pores or passages can provide an increased pass through of the air or fluid into, out of, or within the microporous material.
As can be still further appreciated, the properties of the microporous material can also be defined by a tortuosity of the passages entering into and passing through the material, with relatively small or large passages presenting impeded fluid pathways due the frequency of turns in the passages or by the placement of obstructions in the fluid pathways. The air/fluid passthrough rates of a microporous material can be managed by controlling or defining any of the above-described characteristics of the material to provide a suitable material for use to facilitate pressure control in the eye for the treatment of a disease.
For simplicity, the aforementioned characteristics and variables of the microporous material used in the various embodiments and examples described herein can be presented simply as a porosity which can be based on a volumetric porosity, a pore or passage size, and/or a tortuosity metric. Again, with reference to
At any of these portions of a body portion 200 or 400, the porosity can comparatively range in degree from 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 may range from about 0.01% to 2%, MP may range from about 2% to 20%, and MLP may range from about 20% to 80% that of the size of LP. The size of SP may range from about 0.01 μm to about 1 μm in pore size (as measured as pore diameter or pore average dimension). In some examples, the pore diameter may be a maximum diameter measured across a pore or a maximum cross-sectional length of a pore, and the pore average dimension may be the calculated average of different dimensional lengths as measured across the pore. In some examples, the porosity may increase by about 5 to 10 times as the pore size increases from one category to the next category (for example, from SP to MSP or from MSP to MP, etc.). Assuming, for discussion purposes here, that delivery travels along a relatively straight path through a microporous material so as to sequentially engage porosities of the internal surface 204 or second surface 404, a uniform internal portion, and the external surface 202 or first surface 402, the combined flow resistance can be represented by likewise concatenating their respective porosities. For instance, the internal surface 204 or second surface 404 typically has a low porosity throughout (e.g., to resist tissue ingrowth into the reservoir 206), and portions of the interior portions and the external surface 202 or first surface 402 can have any of the aforementioned degrees of porosity. Under these circumstances when the internal portion has a medium porosity and, for example, the internal portions have a medium porosity and the external surface 202 or first surface 402 has a high porosity, fluid may be delivered through the microporous material from the reservoir 206, for example, to tissue surrounding the device can be represented as SP-MP-LP. More examples are discussed here below.
Various delivery paths can be present within the microporous material. Relatively linear flow paths may comprise regions SP1-SP4-SP5, for example or SP3-MLP1-MP1-MSP1. Although some flow paths may be relatively straight, there are also flow paths that are nonlinear. For instance, under certain conditions, at least some flow may proceed to flow through areas of increasingly less resistance such as SP1-LP1-LP2 or SP3-MLP1-LP1-LP2. As will be appreciated, the microstructure of the microporous materials may undergo modification processes to obtain certain types of flow through the microstructure. For instance, the microstructure may have relatively uniform layers across layered within the microstructure, or as shown here, have variable portions throughout the thickness of the microporous material.
In some examples, the body portion 200 or 400 defines a wall portion thickness extending between the internal surface 204 or second surface 404 (also referred to as a boundary portion) and the external surface 202 or first surface 402 (also referred to as an ingrowth portion). The wall portion thickness can define an intermediate or transition portion 606 of the body portion 200 or 400 located between the boundary portion and the ingrowth portion, the transition portion 606 having a transition porosity that is between a porosity of the low porosity surface (e.g., having smaller pore sizes) of the internal surface 204 or second surface 404 (boundary portion of the thickness) and a porosity of the high porosity surface (e.g., having larger pore sizes) of the external surface 202 or first surface 402 (tissue ingrowth portion of the thickness). In addition, or in alternative, the transition portion 606 can have a transition portion porosity that is equal to porosities of the low porosity surfaces of the internal surface 204 or second surface 404 and the external surface 202 or first surface 402. In addition, or in alternative, the transition portion 606 can have a transition portion porosity that is equal to a porosity of the low porosity surface of the internal surface 204 or second surface 404. In addition, or in alternative, the transition portion 606 can have a transition portion porosity that is equal to a porosity of the high porosity surface of the external surface 202 or first surface 402.
In some examples, the body portion 200, 400 includes a plurality of nodes 600 and fibrils 602. A node may be any section of the external surface 202 or first surface 402 which has a “clump” or larger volume of polymer than a fibril. The node, in some examples, includes sections of the body portion 200, 400 with the small pore size (SP) as explained above with regard to
In at least one of the aforementioned magnifications, any one or more of the features mentioned below in the surfaces, hereinafter referred to as “surface features”, may be observed, when each of the surfaces that are being compared is viewed at the same magnification. In some examples, such features are observed more in the SEM images of the external surface 202 or first surface 402 (
In some examples, the surface features may include a series of pores and/or interstitial spaces adjacent to each other, such as the openings or spaces 604 formed on the surface. For example, the number of pores in the surface 202 or 402 may be greater in number than the surface 204 or 404.
In some examples, the surface features may include roughness as defined by the texture and/or pore sizes on the surface. For example, a roughness (which may be an average roughness) of the surface 202 or 402 may be greater than a roughness of the surface 204 or 404. Definition and determination of surface roughness will be explained in greater detail in view of
In some examples, the surface features may include a difference in depths or a maximum depth as measured with respect to the surface. For example, the surface 202 or 402 may define a greater depth into the body portion from the surface than does the surface 204 or 404. For example, the thickness or depth of the surface 204, 404 may be approximately 10% or less, 20% or less, 30% or less, 40% or less, 50% or less, or any other suitable value or range therebetween with respect to the thickness or depth of the surface 202, 402. The difference in thicknesses or depths may facilitate tissue ingrowth deep into the material and may allow the material to have a relatively thin layer to arrest further tissue ingrowth into the inner surface. Definition and determination of surface depths will be explained in greater detail in view of
The body 200 may be formed of a compliant material having a thickness defining an ingrowth portion such as the first surface 402 that facilitates tissue ingrowth and a boundary portion such as the second surface 404 that prevents or inhibits tissue ingrowth. The ingrowth portion may correspond to the external surface 202, and the boundary portion may define the internal reservoir 206, which may have a fixed internal volume, within the body 200. The ingrowth portion may be characterized by visible microporous surface features at a first magnification, and the boundary portion may be characterized by an absence of visible microporous surface features at the first magnification. As described in association with other embodiments, the first magnification may be 50×, optionally 100×, optionally 500×, or optionally 1000×, or any range or value therebetween.
In some examples, the surface features may be defined by a plurality of fibrils extending between a plurality nodes that present a visually perceptible presence of the fibrils extending between the nodes in the external surface at a predetermined magnification, such as a microstructure defined by a plurality of fibrils extending between a plurality of nodes in which the microstructure is more visible at the external surface than the internal surface, or a fiber microstructure. For example, in the magnifications of
In some examples, the surface features may include a plurality of fibers 1100 forming a microstructure defining a structure of the body portion 200 as shown in
In some examples, the surface feature is less present or minimally present at the surface 204 or 404 than at the other surface 202 or 402 such that the surface feature of the surface 204 or 404 is less visually observable or perceptible at the aforementioned magnification as compared to the other surface 202 or 402. In some examples, the feature may be not observable at all or entirely absent (e.g., the features are not able to be reliably discerned visually) at the surface 204 or 404 at the aforementioned magnification. As a non-limiting, illustrative example,
Referring to the external surface 202 or the first surface 402, the first porosity may be defined by a first average pore size. Such surface may be referred to as a tissue engagement surface. In some examples, the tissue engagement surface has a porosity extending into the engagement surface at an engagement depth to which an external tissue engages, in order to secure or anchor the body portion 200 or 400 at a suprachoroidal location in an eye at which the device 100 is implanted. In some examples, the engaging of the tissue engagement surface with the external tissue is observable after 10 days, 30 days, 50 days, 100 days, or longer. In some examples, sufficient tissue engagement may be defined by having enough cells (or sufficient number of cells) being integrated to affix or secure the implanted device at its location, or to minimize movement of the implanted device from its implanted location. In some examples, the engaging of the tissue engagement surface with the external tissue prevents or inhibits migration of the device 100 from the suprachoroidal location. In some examples, the ingrowth of the external tissue on the tissue engagement surface does not significantly inhibit fluid flow through the body portion 200 or 400. Referring to the internal 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.
The roughness of the surface, therefore, may be defined by the difference between the maximum height and the minimum height as determined using such surface profilometry, in which case the greater the difference, the greater the roughness. For example, the surface roughness of the surface 202, 402 may be defined as having a maximum-to-minimum height difference 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 therein or range therebetween. In comparison, the surface roughness of the surface 204, 404 may be defined as having a maximum-to-minimum height difference of no greater than 10 μm, no greater than 7 μm, no greater than 5 μm, no greater than 4 μm, no greater than 3 μm, no greater than 2 μm, no greater than 1 μm, or any other suitable value therein or range therebetween. In some examples, the total thickness (that is, the distance measured between the maximum height of the external surface 202 or first surface 402 and the maximum height of the internal surface 204 or second surface 404, as appropriate) of the body portion 200 or 400 may be about 100 μm, about 120 μm, about 150 μm, about 170 μm, about 200 μm, or any other suitable value therein or range therebetween. In some examples, the maximum-to-minimum height difference may be defined as a percentage of the total thickness of the body portion 200, 400. For example, the surface 202, 402 may 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 therein or range therebetween, with respect to the total thickness of the body portion 200, 400. In comparison, the surface 204, 404 may have a height difference of no greater than 10%, no greater than 7%, no greater than 5%, no greater than 4%, no greater than 3%, no greater than 2%, no greater than 1%, or any other suitable value therein or range therebetween, with respect to the total thickness of the body portion 200, 400. The surface roughness of the external surface 202 or first surface 402 is greater than the surface roughness of the internal surface 204 or second surface 404.
Also, the depth of a surface may be defined as the maximum depth (or the minimum height, as measured by in
In
In
In some examples, the first and second portions 1500 and 1502 have different porosities with respect to each other. For example, the second portion 1502 may be more porous than the first portion 1500 to allow fluid to more readily enter the body portion 400 through the second (or internal) portion 1502. In some examples, the first and second portions 1500 and 1502 are made of different materials or different components that are combined together. In some examples, the first and second portions 1500 and 1502 are made of a single or unitary piece of material that is treated to form regions of different porosities. In some examples, the first and second portions 1500 and 1502 may include a transitional portion therebetween, such that the porosity changes gradually between the first and second portions 1500 and 1502, in which case the transitional portion may have one or more porosities that are greater than a porosity of the first portion 1500 and less than a porosity of the second portion 1502. Porosity may be measured using any suitable measurement, including but not limited to calculating average pore sizes, measuring the time it takes for a predetermined amount of fluid (such as water) to pass through the portions, and/or measuring the time it takes for a predetermined amount of gas (such as air) to pass through the portions at a predetermined pressure, for example.
The aforementioned configurations differ from the examples shown in lanchulev T, et al., such as CyPass®, iStent Supra®, MINIject®, and BioStent®. For example, CyPass® and iStent Supra® are described as rigid and non-conforming, whereas BioStent® is made using biotissue such as the decellularised scleral allograft tissue, which may lose the effect of maintaining a drainage pathway for aqueous humor to flow from the anterior chamber of the eye over time as the biotissue is absorbed into the tissue surrounding the device. The MINIject®, on the other hand, is manufactured such that the sizes of the connections between pores are controlled with high uniformity throughout the entire volume of the device, thereby having a uniform internal pore size of 27 μm, as explained in Grierson 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. Beneficially, in some examples, having variable pore sizes or porosities throughout the device 100 may beneficial in providing a plurality of different drainage pathways for the fluid to pass through the device 100 as explained above, in order to better reduce the IOP.
Various methods of controlling fluid pressure within an eye may be contemplated using the suprachoroidal implantable device 100 as disclosed herein. For example, the device 100 may be provided by the practitioner or surgeon and the disposed in a subconjunctival location of the eye as shown in any one of
In view of
In some examples, the sealable conduit 300 described in association with
The device 100 described in association with
Various methods of manufacturing the suprachoroidal implantable device 100 may be contemplated as disclosed herein. For example, a suitable compliant material is provided, and the body portion 200 or 400 of the body portion is formed using the compliant material, such that the body portion 200 or 400 has the external surface 202 or first surface 402 as well as the internal surface 204 or second surface 404 as described above.
In some examples, such as the devices 100 shown in
In some examples, such as the devices 100 shown in
In some examples, referring to
Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present disclosure. For example, while the embodiments described above refer to particular features, the scope of this disclosure also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present disclosure is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.
The present application claims the benefit of U.S. Provisional App. No. 63/471,916 filed Jun. 8, 2023, and U.S. Provisional App. No. 63/657,028 filed Jun. 6, 2024, which are incorporated herein by reference in their entireties for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63471916 | Jun 2023 | US | |
| 63657028 | Jun 2024 | US |
