Ciliary groove implants and methods for using ciliary groove implants

Abstract

This disclosure provides an ophthalmic implant, such as a ciliary sulcus implant, which may include one or more drug delivery devices. [Solution] The ophthalmic implant comprises a ring or partial ring comprising a first material and configured for implantation in the target eye, characterized by an outer surface, an inner wall, and a central opening, and a haptic comprising a second material and attached to the ring or partial ring at a first haptic end. The first and second materials have different chemical compositions, and one of the ring or partial ring and the haptic is more rigid than the other. The ophthalmic implant further comprises at least one drug delivery structure disposed within the ring or partial ring and containing a polymer matrix and a therapeutic agent disposed therein.

Description

Technical Field

[0001] The present invention relates to a ciliary sulcus implant and a method of using a ciliary sulcus implant.

Background Art

[0002] Conventional intraocular implants may have limitations in terms of their manufacturability and their ability to provide a therapeutic effect without damaging eye tissue when implanted. Thus, there are unmet requirements for intraocular implants that provide improved safety during use and reduced tissue damage, as well as improved manufacturability.

Summary of the Invention

Problems to be Solved by the Invention

[0003] This specification provides an intraocular implant that can be implanted into a subject's eye. In some cases, this specification provides an intraocular implant for implantation into the ciliary sulcus or capsular bag of a subject's eye.

Means for Solving the Problems

[0004] In various embodiments, the ophthalmic implant comprises a ring or partial ring 15 that includes a first material and is configured for implantation into a subject's eye, characterized by an outer peripheral surface, an inner wall, and a central opening 17, and a closed-loop haptic 16, 16C, 16L, 43, 46 that includes a second material and is attached to the ring or partial ring at a first haptic end 16d, 41, 45 and a second haptic end 16d, 42, 44. The first material and the second material have different chemical compositions, and the ring or partial ring is more rigid than the closed-loop haptic.

[0005] In some embodiments, under conditions present in the eye after implantation, the ring or partial ring retains its shape, while the closed-loop haptic deforms. In other embodiments, with an applied force of 100 mN, the ring or partial ring retains its shape, while the closed-loop haptic deforms. In yet another embodiment, with an applied force of 10 mN, the ring or partial ring retains its shape, while the closed-loop haptic deforms.

[0006] In certain embodiments, the ophthalmic implant comprises multiple closed-loop haptics. In some embodiments, the first haptic end is flexibly connected to the ring at the first haptic end such that the closed-loop haptic is deformable by forces applied by the tissue in which the implant is embedded.

[0007] In another embodiment, a portion of the closed-loop haptic passes through the holes 18, 49, 50, 84 of the ring and enters the central opening to form the gripping features 21, 85. In some embodiments, the second haptic end is flexibly connected to the ring at the second haptic end so that the closed-loop haptic can be deformed by forces applied by the tissue in which the implant is embedded.

[0008] In some embodiments, the closed-loop haptic is configured such that a first haptic end, a second haptic end, or a combination thereof is positioned within a recess of the ring 15.

[0009] In other embodiments, the first haptic end is attached to the ring by mechanically fixing the first haptic end to the ring, overmolding the first haptic end to the ring, fusing the first haptic end to the ring, attaching the first haptic end to the ring by heat shrink attachment, attaching the first haptic end to the ring with adhesive, or a combination thereof.

[0010] In certain embodiments, the second haptic end is attached to the ring by mechanically fixing the second haptic end to the ring, overmolding the second haptic end to the ring, fusing the second haptic end to the ring, attaching the second haptic end to the ring by heat shrink attachment, attaching the second haptic end to the ring with adhesive, or a combination thereof.

[0011] In some embodiments, the first material is a biocompatible material, and the second material is a biocompatible material. In other embodiments, the first material is a first polymer, and the second material is a second polymer. In certain embodiments, the first material is selected from the group consisting of silicone, acrylic resin, hydroxyethyl methacrylate (HEMA), polyethyl methacrylate (PEMA), and polyethyl acrylate (PEA), or any combination thereof.

[0012] In some embodiments, the second material is an elastomer. In other embodiments, the second material is selected from the group consisting of polymethyl methacrylate (PMMA), polyvinylidene fluoride (PVDF), polypropylene (PP), and polyethersulfone (PES), or any combination thereof.

[0013] In various embodiments, an ophthalmic implant comprises a ring or partial ring 15 configured for implantation in a patient's eye, characterized by an outer surface, an inner wall, and a central opening 17, and haptics 16, 16L, 43, 46 connected to the ring at first haptic ends 16d, 41, 43 and second haptic ends 16d, 42, 44. The haptics are flexibly connected to the ring at the first haptic ends so that they are deformable by forces applied by the tissue in which the implant is embedded.

[0014] In some embodiments, the haptic is flexibly connected to a ring at a second haptic end so that the haptic can be deformed by forces applied by the tissue in which the implant is embedded.

[0015] In another embodiment, the haptic is configured such that a first haptic end, a second haptic end, or a combination thereof is positioned within the recesses 37, 52, 53 of the ring 15.

[0016] In certain embodiments, the ring includes holes 18, 36, 47, 48, 49, 50, 52, and 53 that extend from openings 19, 51, 56, and 57 on its outer surface toward the inner wall. In some embodiments, second haptic ends 16d, 42, and 44 are slidably positioned within the holes 18, 36, 48, 50, and 52.

[0017] In various embodiments, ocular implants are configured to be implanted in the posterior chamber and ciliary sulcus of the eye in question. In some embodiments, the second haptic end is flexibly connected to the ring at the second haptic end so that the haptic can be deformed by forces applied by the tissue in which the implant is embedded.

[0018] In certain embodiments, the second haptic end is attached to the ring by mechanically fixing the second haptic end to the ring, overmolding the second haptic end to the ring, fusing the second haptic end to the ring, attaching the second haptic end to the ring by heat shrink attachment, attaching the second haptic end to the ring with adhesive, or a combination thereof.

[0019] In various embodiments, the Disclosure provides an ophthalmic implant configured for implantation in a target eye. The ophthalmic implant comprises a ring 15 configured for implantation in a target eye, characterized by an outer surface, an inner wall, and a central opening 17, and haptics 16, 16L, 43, 46 connected to the ring by first haptic ends 16d, 41, 45 and second haptic ends 16d, 42, 44. The ring comprises holes 18, 49, 50 extending from openings 19, 51 on the outer surface toward the inner wall. The second haptic ends 16d, 42, 44 are positioned within and slidably within the holes 18, 48, 50, 52, so that the haptics are deformable by forces applied by the tissue into which the implant is embedded, which can act to push the second haptic ends into the holes 18, 48, 50, 52.

[0020] In various embodiments, the Disclosure provides an ophthalmic implant configured for implantation in the posterior chamber and ciliary sulcus of a target eye. The ophthalmic implant comprises a ring 15 configured for implantation in the posterior chamber of a target eye, characterized by an outer surface, an inner wall, and a central opening 17, and haptics 16, 16L, 43, 46 connected to the ring by first haptic ends 16d, 41, 45 and second haptic ends 16d, 42, 44, the ring having holes 18, 49, 50 extending from openings 19, 51 on the outer surface toward the inner wall, the second haptic ends 16d, 42, 44 being positioned within and slidably within the holes 18, 48, 50, 52, the haptics being deformable by forces applied by the tissue into which the implant is implanted, which can act to push the second haptic ends into the holes 18, 48, 50, 52.

[0021] In some embodiments, the second haptic ends 16d, 42, 44 include a haptic distal tip 16T having a larger cross-section than the remainder of the second haptic ends 16d, 42, 44.

[0022] In other embodiments, the second haptic ends 16d, 42, 44 include a haptic distal tip 16T having a cross-section larger than the remainder of the second haptic ends 16d, 42, 44, and the through-holes 18, 36, 48, 50 have lumens with cross-sections smaller than that of the haptic distal tip 16T, whereby the second haptic ends are prevented or blocked from passing through the through-holes.

[0023] In some embodiments, the ophthalmic implant further includes a gripping feature 21 disposed on the second haptic ends 16d, 42, 44, and the gripping feature is configured for engagement with a gripping instrument.

[0024] In other embodiments, the holes 18, 50 that communicate from an opening 19, 51 in the outer peripheral surface towards the inner wall are through-holes that communicate with openings 20, 56 in the inner wall of the ring, and the second haptic ends 16d, 42, 44 include a haptic distal tip 16T having a cross-section larger than the remainder of the second haptic ends 16d, 42, 44, and the haptic distal tip 16T is disposed in the central opening 17.

[0025] In a further embodiment, the first haptic ends 16d, 41, 45 include a haptic distal tip 16T having a cross-section larger than the remainder of the first haptic ends 16d, 41, 45.

[0026] In some embodiments, the first haptic ends 16d, 41, 45 include a haptic distal tip 16T having a cross-section larger than the remainder of the first haptic ends, and the through-holes 18, 47, 49 have lumens with cross-sections smaller than that of the haptic distal tip 16T, whereby the first haptic ends are prevented or blocked from passing through the through-holes.

[0027] In other embodiments, the ophthalmic implant further includes a gripping feature 21 disposed on the first haptic ends 16d, 41, 45, and the gripping feature is configured for engagement with a gripping instrument.

[0028] In certain embodiments, the holes 18, 49 that lead from the openings 19, 51 on the outer peripheral surface towards the inner wall are through holes that communicate with the openings 20, 57 on the inner wall of the ring, and the first haptic ends 16d, 41, 45 include a haptic distal tip 16T having a cross-section larger than the remainder of the first haptic end, and the haptic distal tip 16T is disposed in the central opening 17.

[0029] In some embodiments, the holes 18, 52, 53, 49, 50 are radially oriented within the ring. In other embodiments, the holes 18, 52, 53, 49, 50 are chordally oriented within the ring. In further embodiments, the holes 18, 49, 50 are through holes that communicate with an opening on the inner wall or the front face of the ring. In additional elements, the holes 18, 52, 53 are blind holes that terminate at the ring.

[0030] In some aspects, the first haptic end is flexibly connected to the ring at the second haptic end such that the haptic can be deformed by a force applied by the tissue into which the implant is implanted.

[0031] In certain embodiments, the first haptic end is attached to the ring by mechanically fixing the first haptic end to the ring, overmolding the first haptic end with the ring, fusing the first haptic end to the ring, attaching the first haptic end to the ring by heat shrink fitting, attaching the first haptic end to the ring by an adhesive, or a combination thereof.

[0032] In other aspects, the ring includes a first biocompatible material and the haptic includes a second biocompatible material. In some embodiments, the first biocompatible material and the second biocompatible material have different chemical compositions, and the ring or partial ring is more rigid than the haptic.

[0033] In some embodiments, under conditions present in the eye after implantation, the ring or partial ring retains its shape, while the closed-loop haptic deforms. In some embodiments, with an applied force of 100 mN, the ring or partial ring retains its shape, while the closed-loop haptic deforms. In other embodiments, with an applied force of 10 mN, the ring or partial ring retains its shape, while the closed-loop haptic deforms.

[0034] In certain embodiments, the first biocompatible material is a first polymer, and the second biocompatible material is a second polymer. In some embodiments, the first biocompatible material is selected from the group consisting of silicone, acrylic resin, hydroxyethyl methacrylate (HEMA), polyethyl methacrylate (PEMA), and polyethyl acrylate (PEA), or any combination thereof.

[0035] In some embodiments, the second biocompatible material is an elastomer. In certain embodiments, the second biocompatible material is selected from the group consisting of polymethyl methacrylate (PMMA), polyvinylidene fluoride (PVDF), polypropylene (PP), and polyethersulfone (PES), or any combination thereof.

[0036] In some embodiments, the ophthalmic implant further comprises a drug delivery structure. In certain embodiments, the ophthalmic implant further comprises a lens 34 positioned within a central opening 17.

[0037] In various embodiments, the ophthalmic implant comprises a first arch-shaped drug delivery structure and a second arch-shaped drug delivery structure 70 configured for implantation in the target eye, having an outer contour 70C configured for placement in the ciliary sulcus, and containing a therapeutic agent configured to treat a condition or disease of the target eye; and a first biasing member and a second biasing member 71 connecting the first arch-shaped drug delivery structure and the second arch-shaped drug delivery structure, configured to be elastically expandable and compressible so as to bias the first drug delivery structure and the second drug delivery structure away from each other to form a large-diameter ciliary sulcus implant, and so as to allow compression of the ciliary sulcus implant to a small-diameter form.

[0038] In various embodiments, an ophthalmic implant comprises an arch-shaped drug delivery structure 70 configured for implantation in the ciliary sulcus of a target eye, having an outer contour 70C configured for placement in the ciliary sulcus, and containing a therapeutic agent configured to treat a condition or disease of the target eye; and a biasing member 71 connected to the arch-shaped drug delivery structure, configured for implantation in the ciliary sulcus of a target eye, and configured to be elastically expandable and compressible to bias the arch-shaped drug delivery structure away from one end of the biasing member to configure the ciliary sulcus implant into a large-diameter shape, and to allow compression of the ciliary sulcus implant into a small-diameter shape.

[0039] In various embodiments, the ophthalmic implant comprises a drug delivery structure having an elastically expandable and compressible wire frame 80 and panels 81, 82 connected by a support column 83, wherein the panels and support column define an opening, and a portion of the compressible wire frame is positioned within the opening.

[0040] In some embodiments, the ophthalmic implant is configured to elastically expand until its outer contour contacts the ciliary sulcus of the eye. In some embodiments, the arc-shaped drug delivery structure 70 contains a therapeutic agent.

[0041] In certain embodiments, the drug delivery structures 27, 81, 82 contain a therapeutic agent. In certain embodiments, the drug delivery structure is selected from the group consisting of a therapeutic agent, a therapeutic agent disposed in a matrix, an erodible therapeutic agent, and a therapeutic agent in a matrix forming a drug-eluting structure, or a combination thereof. In some embodiments, the drug delivery structure 27 is disposed on the rear surface 15P of the ring 15. In certain embodiments, the therapeutic agent is disposed in a matrix forming a drug-eluting structure. In some embodiments, the drug delivery structure is disposed within the ring or partial ring 15 or within the arc-shaped drug delivery structure 70. In some embodiments, the drug delivery structure or the arc-shaped drug delivery structure 70 includes a polymer matrix containing the therapeutic agent. In certain embodiments, the polymer matrix is ​​bioerodible. In further embodiments, the therapeutic agent comprises one or more of the following: prostaglandin analogs, alpha agonists, Rho-kinase (ROCK) inhibitors, adenosine receptor agonists, carbonic anhydrase inhibitors, adrenergic and / or cholinergic receptor activators, steroids, aptamers, complement factors, antioxidants, anti-inflammatory agents, antibodies, antiproliferative agents, antimitotic agents, or anti-inflammatory agents. In certain embodiments, the prostaglandin analog comprises bimatoprost.

[0042] In various embodiments, this disclosure provides a method for treating an ocular condition or disease in a subject requiring treatment. The method includes preparing an ocular implant as described herein and treating an ocular condition or disease in the subject by implanting the ocular implant into the eye of the subject.

[0043] In some embodiments, the method includes compressing an ophthalmic implant into an injector, inserting a portion of the injector into the target eye, and releasing the ophthalmic implant into the target eye. In other embodiments, the method includes implanting the ophthalmic implant into the posterior chamber and ciliary sulcus of the target eye. In other embodiments, the method includes implanting the ophthalmic implant into the lens capsule of the target eye.

[0044] In other embodiments, the method further includes delivering a therapeutic agent from an ophthalmic implant to the target eye tissue. In certain embodiments, the therapeutic agent is delivered by eluting the therapeutic agent from a matrix containing the therapeutic agent. In further embodiments, the therapeutic agent is a prostaglandin analog. In additional embodiments, the therapeutic agent is bimatoprost.

[0045] In some embodiments, the eye condition or disease is selected from the group consisting of age-related macular degeneration, amblyopia (lazy eye), cataracts, color blindness, diabetic retinopathy, dry eye, floaters, glaucoma, conjunctivitis, refractive errors, and retinal detachment, or a combination thereof. In a particular embodiment, the eye condition or disease is glaucoma.

[0046] In certain embodiments, the subject had previously received an intraocular device implanted in the lens capsule of the subject's eye. In another embodiment, the method further includes manipulating the device in the eye using the gripping features 21,85.

[0047] In some embodiments, the disclosure provides an ophthalmic implant comprising a ring configured for implantation in a patient's eye and a passage 18 communicating from an opening 19 adjacent to the circumferential surface of the ring to an opening 19 adjacent to the inner wall of the ring.

[0048] In other embodiments, the Disclosure provides an ophthalmic implant comprising a ring configured for implantation in the posterior chamber of a patient's eye and a passage 18 communicating from an opening 19 near the circumferential surface of the ring to an opening 19 near the inner wall of the ring. In various embodiments, the Speculation provides a method for treating a condition of the eye in question. The method includes preparing an ophthalmic implant comprising a ring configured for implantation in the lens capsule of the eye in question and a passage 18 communicating from an opening 19 near the circumferential surface of the ring to an opening 19 near the inner wall of the ring, and implanting the ring in the lens capsule of the eye such that the passage allows aqueous humor to flow from the inner wall of the ring to the opening 19 near the circumferential surface of the ring, so that a therapeutic agent can flow from the central opening to the equator of the lens capsule. In some cases, such a method may further include a drug delivery structure fixed to the ring, the drug delivery structure containing bimatoprost, and the method involves implanting the ophthalmic implant to treat glaucoma. In some cases, such a method may further include a drug delivery structure fixed to a ring, the drug delivery structure containing a therapeutic agent capable of functioning to inhibit the proliferation and activity of lens endothelial cells in the equatorial and posterior capsules of the lens capsule, and the method involves implanting an ophthalmic implant to inhibit the proliferation and activity of lens endothelial cells in the equatorial and posterior capsules of the lens capsule.

[0049] All publications, patents, and patent applications cited herein are incorporated herein by reference to the same extent as when each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference.

[0050] Novel features of the present invention are specifically described in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description and accompanying drawings illustrating exemplary embodiments in which the principles of the present invention are utilized. [Brief explanation of the drawing]

[0051] [Figure 1]A diagram illustrating the operating environment of an intraocular drug delivery system. [Figure 2] A diagram illustrating the operating environment of an intraocular drug delivery system. [Figure 3] Figure 2 shows a drug delivery platform configured for use in the ciliary sulcus of the eye. [Figure 4] Side view of Figure 3. [Figure 5] Figures 2 and 3 show forward perspective views of the drug delivery platform. [Figure 6] This shows a drug delivery system configured to allow posterior access to the haptic tip. [Figure 7] This shows a drug delivery system configured to allow posterior access to the haptic tip. [Figure 8] A diagram showing the ciliary groove (sulcus) IOL, which is constructed with the characteristics of a captured haptic tip. [Figure 9] Side views showing the front opening of the through-hole of the device in Figures 6-8. [Figure 10] Figures 2-7 show modified examples that may be applied to the devices. [Figure 11] A diagram showing a drug delivery platform combined with an implant configured for use in the ciliary sulcus of the eye, which has one or more aqueous humor flow holes. [Figure 12] Figure 11 shows a forward perspective view of the drug delivery platform. [Figure 13] Figure 11 shows a forward perspective view of the drug delivery platform. [Figure 14] A diagram showing the ciliary sulcus lens modified by the aqueous humor opening. [Figure 15] A figure showing a drug delivery ciliary sulcus implant configured for use in the ciliary sulcus of the eye, according to an embodiment of the present disclosure. [Figure 16] Figure 15 shows a drug delivery ciliary groove implant in a compressed form according to an embodiment of the present disclosure. [Figure 17] A diagram showing a drug delivery platform in which a biasing member is integrally formed with a drug delivery structure according to an embodiment of the present disclosure. [Figure 18] Figure 17 shows a compressed form of a drug delivery platform in which a biasing member is integrally formed with a drug delivery structure according to an embodiment of the present disclosure. [Figure 19] A diagram showing a drug delivery platform having a single arc-shaped drug delivery structure according to an embodiment of the present disclosure. [Figure 20] A diagram illustrating a drug delivery platform comprising a drug delivery device having an elastically expandable and compressible wireframe according to an embodiment of the present disclosure. [Figure 21] A diagram illustrating a drug delivery platform comprising a drug delivery device having an elastically expandable and compressible ring according to an embodiment of the present disclosure. [Figure 22] This diagram shows a drug delivery platform comprising a drug delivery device having an elastically expandable and compressible ring according to an embodiment of the present disclosure, with the device shown in Figure 21 in a compressed state. [Figure 23] A diagram illustrating a drug delivery platform comprising closed-loop haptics and A-shaped haptics according to an embodiment of the present disclosure. [Figure 24] A diagram illustrating a drug delivery platform comprising closed-loop haptics and retention features according to an embodiment of the present disclosure. [Figure 25] A diagram illustrating a drug delivery platform comprising closed-loop haptics and A-shaped haptics according to an embodiment of the present disclosure. [Figure 26] A diagram illustrating a drug delivery platform comprising multiple closed-loop haptics attached to a compressible partial ring according to an embodiment of the present disclosure. [Figure 27] A diagram showing a drug delivery platform in which a biasing member is integrally formed with a drug delivery structure according to an embodiment of the present disclosure. [Modes for carrying out the invention]

[0052] This disclosure provides intraocular devices for implantation in a target eye. The devices provided herein can be implanted in various regions of the target eye. In various embodiments, this specification provides intraocular devices for implantation in the ciliary sulcus of a target eye, as described herein.

[0053] As used herein, unless otherwise defined, terms such as “ophthalmic device,” “ophthalmic implant,” and “intraocular device” may be used interchangeably and generally refer to a device that can be implanted in one or more specific locations in the eye of a subject (e.g., a human eye).

[0054] Figures 1 and 2 show the arrangement and use of an intraocular drug delivery system or other ocular implant in the eye in question. Eye 1 comprises the lens 2 and lens capsule 3, an anterior chamber 4 containing the cornea 5 and iris 6, and aqueous humor filling the space between the cornea and iris, and a posterior chamber 7 between the iris and lens capsule. The posterior space / vitreous humor 8 is the large space between the lens and the retina 9. The natural lens 2 of the eye is characterized by the optical axis 10. The ciliary sulcus 11 is an annular space surrounding the posterior chamber, located between the posterior surface of the iris 6 and the anterior surface of the ciliary body 12. (In the following description of the intraocular implant, the terms posterior and anterior are used in reference to the anatomical structure of the eye, where the cornea is anterior and the retina is posterior). The aqueous humor nourishes the lens and cornea and maintains intraocular pressure. The aqueous humor flows inward in the ciliary sulcus between the lens capsule / lens and the iris, then forward through the opening of the iris into the anterior chamber (the open space between the iris and lens and the cornea), and then radially outward between the iris and the cornea, where it is drained through structures within the sclera (specifically, Schlemm's canal and veins within the sclera (not shown)).

[0055] Figure 2 shows the placement of the ciliary sulcus implant / drug delivery platform 13 in the eye. In many cases in which the ciliary sulcus implant / drug delivery platform is implanted, the subject may already have an intraocular lens 14 placed in the lens capsule after the removal of the natural lens. In this example, the ciliary sulcus implant / drug delivery platform is provided in the form of a ring 15 and is implanted in the posterior chamber 7 and ciliary sulcus 11, either alone or in conjunction with another implant. As shown in Figure 2, the ciliary sulcus implant / drug delivery platform 13 is positioned in the ciliary sulcus of the posterior chamber 7, posterior to the iris 6 and anterior to the ciliary body 12, or more generally, anterior to the anterior lens capsule. The ciliary sulcus implant / drug delivery platform 13 is held in place by a haptic 16 fixed to the ciliary sulcus implant / drug delivery platform 13, which engages with the tissue of the ciliary sulcus and is configured to keep the ciliary sulcus implant / drug delivery platform 13 centered with respect to the optical axis 10 of the eye. The haptic adapts to various diameters of the ciliary sulcus and is elastically biased outward to expand after implantation until it contacts the tissue on the margin of the ciliary sulcus. The ciliary sulcus can have the following dimensions: 11.55 ± 0.38 mm at 45 degrees, 11.99 ± 0.36 mm at 90 degrees, 11.54 ± 0.36 mm at 135 degrees, and 11.32 ± 0.40 mm at 180 degrees, with the vertical diameter being greater than the horizontal diameter, having an average difference of approximately 0.67 ± 0.26 mm (range, 0.36 to 1.13 mm) between the vertical and horizontal diameters.

[0056] I. Intraocular Implants This specification provides intraocular implants that may comprise one or more U-loop haptics as described herein. In some embodiments, such an intraocular implant is a ciliary sulcus implant (for implantation in, for example, the ciliary sulcus of the eye of interest) comprising one or more U-loop haptics. In an embodiment, Figure 3 is a front view of the ciliary sulcus implant / drug delivery platform of Figure 2. The drug delivery platform comprises a planar front surface 15A and a rear surface 15P (for example, as shown in Figure 4), a drug delivery structure 27, and a ring 15 which may be flat as a washer and has a central opening 17. In other embodiments, each of the front surface 15A and the rear surface 15P may not be independently planar and may have a rounded apex instead of an acute radius at the ends. The ring 15 preferably (for example in this embodiment) has a radially oriented through-hole 18 between the front and rear surfaces of the ring, communicating from an opening 19 on the outer circumference of the ring to the inner surface of the ring and an opening 20 on the inner wall of the ring, without communicating with either the front or rear surface of the ring. In some embodiments, the radially oriented through-hole 18 may be replaced by an opening (without a rear surface) having only a front cover. In this embodiment, the rear surface is located in close contact with the front surface of the lens capsule and forms a through-hole that holds the distal tip of the haptic.

[0057] The base portion 16B ("first end") of the haptic is fixed to the ring by any suitable method, including mechanically fixing the haptic to the ring, overmolding the haptic with the ring, fusing the haptic to the ring, attaching the haptic to the ring by heat shrink attachment, attaching the haptic to the ring by adhesive, or by any other suitable attachment such that it cannot move relative to the ring. The haptic 16 has a loop portion 16L and a "free end" or tip portion 16T ("second end" or "end portion") away from the haptic base portion 16B. The loop portion extends radially from the joint of the haptic base portion 16B with the ring, curves back to the ring, where the haptic tip portion 16T enters a through hole 18, preferably passing through the through hole so that the tip portion is exposed within the central opening 17. U-loop haptics or horseshoe haptics differ from typical C-loop and J-loop haptics in that the haptic arcs from the base so that the loop portion extends along an arc sufficient to return to the ring and enter the through-hole (and preferably extend through the through-hole into the central opening), and differ from plate haptics or loop haptics in that the tip is not fixed to the ring in a way that prevents movement.

[0058] The tip may preferably be configured to facilitate engagement with a Sinskey hook, micro-gripping forceps, or other instruments. As shown, the tip consists of a gripping feature 21 such as an eyelet, but other forms may be used, such as a pinhole (formed to accommodate a Sinskey hook), any serrations, flanges, hooks, wrench flats, or other planes that can be gripped by micro-gripping forceps. If other suitable gripping instruments are available, or if the operations described below are not anticipated, the tip may be terminated at a blunt end without any gripping features.

[0059] The distal end 16d of the haptic, including the tip 16T and a short portion proximal to the tip, is configured to be loosely positioned within the radial through-hole 18, and accordingly, the radial through-hole is configured to loosely receive the distal end 16d of the haptic, including the tip 16T. The distal end of the haptic, particularly the portion positioned within the radial through-hole, has dimensions corresponding to the anterior-posterior dimension (arrow 22 in Figure 4), the periphery of a ring formed to a size related to the anterior-posterior dimension of the radial through-hole (arrow 24 in Figure 4) (arrow 23 in Figure 4), and the circumferential width of the through-hole (arrow 25 in Figure 3), allowing the distal end 16d to slide within the through-hole, and the distal end 16d can move radially (or longitudinally) within the through-hole. The gripping feature 21 can be made larger in one or the other dimension (arrow 26 in Figure 4) than the corresponding dimension of the radial through-hole to prevent the distal tip from slipping out of the radial through-hole and becoming detached from the ring (preferably the gripping feature acts as a mechanical stopper to prevent the haptic from slipping radially out of the through-hole). The illustrated eyelet has a diameter larger than, for example, the circumferential width identified by arrow 25 of the through-hole. This configuration results in a reduction of the radially inward force applied to the haptic loop by the edge of the ciliary groove. These forces act to push the tip 16T and distal end 16d of the haptic into the through-hole and toward / into the central opening, avoiding the transfer of radially inward forces to the ring, which could otherwise deform the ring. The result of the radially inward force on the haptic is shown in Figure 3 by dashed lines, where the distal end 16d and the gripping feature 21 are radially displaced. Furthermore, because the distal tip is confined within the through-hole, the tip is not pressed into the iris or ciliary body by forces applied by anatomical structures or manipulations during implantation or removal, as is the case with C-loop or J-loop haptic devices. This minimizes or eliminates the risk of trauma caused by the tip.Furthermore, as described below, the gripping feature can be used to pull the haptic out of the ciliary groove and detach the haptic from the iris and ciliary body, eliminating the need to insert the instrument into the ciliary groove and pass the tip of the instrument over these structures.

[0060] Therefore, there is no need to insert the instrument into the ciliary sulcus or posterior chamber, and the haptic can be dislodged from the ciliary sulcus position without engaging with the iris or surrounding tissue, lifted above the mounting plane for easier removal, and thus minimizes trauma to associated tissue. These haptic loops can also assist in positioning the device during initial implantation, so that the haptic can be drawn (towards the geometric center of the entire device) and then released (allowed to open into the ciliary sulcus) when the ring is properly positioned. The constrained nature of the haptic will also make it easier to fold the device for insertion into the eye, and its reproducibility will be higher. This is because the haptic is constrained in a known space and axis, and therefore it will be easier to compress the device in the injector and then inject or place it into the eye.

[0061] Figure 4 is a side view of the drug delivery platform of Figures 2 and 3, showing the height of the through-hole and the front-to-back dimensions of the haptic, which may closely match. The outer circumferential surface 15C is also shown. The haptic tip and gripping feature may have a front-to-back dimension greater than the front-to-back dimension of the through-hole. In this side view, the drug delivery structure 27 is shown on the rear surface 15P of the ring 15. The front surface 15A is substantially flat in this illustration, which is preferred to minimize iris irritation. The front surface may be smoothly curved but may not have protrusions such as drug delivery devices and / or compartments shown in other figures. Figure 5 is a front perspective view of the device of Figure 4. The drug delivery structure may also be positioned in a recess on the front surface of the ring and consist of a surface that follows a flat or smoothly curved front surface, and may be configured such that the front surface of the drug delivery structure fits within the recess without extending forward beyond the front surface of the ring. The angle α of the haptic's inclination angle or vault angle relative to the plane of the ring is preferably about 0° to about 20°, about 0° to about 10°, or 0° to about 5° from the base of the haptic forward.

[0062] The drug delivery structure may be arranged as shown in Figure 3, but may also be arranged around the ring, for example, radially aligned, or close to the haptic base and haptic opening, or around the entire circumference of the rear surface of the ring (Figure 10). The drug delivery structure can also function as a structural element that enhances the stability / rigidity of the very thin silicone, and may be arranged to enhance the ability of the silicone ring to maintain an open state (i.e., to minimize deformation from its unconstrained circular form and avoid or minimize "ellipsification" after implantation). The haptic base may also extend further into the silicone body to further enhance the stability of the ring. The haptic base shown in Figure 3 can extend into the ring and circumferentially into the ring to stabilize the ring. If the haptic is made of a material that is more rigid than the ring, which may preferably be formed from silicone, extending it into the ring helps to increase the rigidity of the assembled haptic and ring.

[0063] On the rear surface 15P, the drug delivery platform may include one or more drug delivery structures 27. The drug delivery structures may be directly fixed to the rear surface, or they may be placed in compartments.

[0064] A drug delivery structure configured for placement on a ring may be provided as a drug depot or drug mass in the form of a block, plate, wafer, or the like, containing a therapeutic agent or a therapeutic agent placed in a matrix, and may contain an erosive therapeutic agent or a therapeutic agent in a matrix forming a drug-eluting structure.

[0065] Figure 6 shows a drug delivery system configured to allow posterior access to the haptic tip. Figures 7 and 8 show drug delivery systems configured to allow access to the haptic tip. If it is desired that the central opening be closed with, for example, a lens or other component, the haptic tip and through-hole can be configured according to Figures 6 and 7, which have the advantage of minimizing the transfer of radial compressive forces applied to the haptic by the surrounding tissues of the eye and eliminating the possibility of trauma to the iris by the haptic tip during implantation and removal, while retaining the functionality of grasping the haptic tip to release the haptic from the ciliary sulcus. In Figure 6, the through-hole communicates from an opening 19 on the front surface 15A of the ring to a posterior opening 32P on the rear surface 15A of the ring. The ring may include a drug delivery structure 27 disposed within the ring. The ring includes a hole 32 to which the haptic tip 16T (at the distal end 16d of the haptic) can extend. The gripping feature portion 21 may extend rearward and radially inward beyond the rear opening 32P, as shown in Figure 6, or the gripping feature portion 21 may be positioned completely below the front surface of the ring in the recess of the front opening 32A, as shown in Figure 7. In Figure 7, the haptic tip portion 16T and the gripping feature portion 21 are positioned completely within the recess and completely behind the front surface (i.e., they do not protrude forward from the front surface of the ring (the bottom of the recess is not considered part of the front surface of the ring)). The haptic can be in the form of a loop 16L. As shown in Figure 7, the central opening may be equipped with a lens component 33 to form a lens for implantation in the ciliary sulcus, such as an implantable collamer lens (ICL), or an IOL for implantation in the target lens capsule.

[0066] Figure 8 illustrates the features of an embodiment of a drug delivery platform having an implantable haptic tip in an IOL, comprising a lens 34 and an optional minimal ring 15 used to support the IOL lens. In this figure, the distal haptic end 16d and haptic tip 16T of the haptic 16, as well as the haptic base 16B, may be located in a through-hole 36 that communicates radially inward with the rear opening from the rear surface of the lens near the periphery of the lens or frame to the opening and recess 37 of the front surface 38 of the lens, and the haptic tip is located entirely within the recess 37 and entirely behind the front surface (i.e., it does not protrude forward of the front optical surface of the lens (the bottom of the recess is not considered part of the front optical surface of the lens)), so that the haptic tip does not come into contact with the iris but is still accessible for grasping with a hook or grasping forceps and is still slidable within the through-hole to relieve compressive forces applied to the haptic by surrounding tissue. Figure 9 is a side view of a drug delivery platform or ciliary sulcus IOL showing a through-hole terminating at an opening on the front surface of the ring or lens, as described with respect to Figures 6, 7, and 8. Similar to the device in Figure 8, this device comprises an IOL that can be implanted in the ciliary sulcus or lens capsule of the target.

[0067] Figure 10 shows a modified example that may be applied to the devices in Figures 2 to 9 above. Two different forms of through holes are shown in Figure 10. Each end 41, 42 of haptic 43 and each end 44, 45 of haptic 46 are slidably positioned within holes 47, 48, 49, 50 that are chord-oriented (i.e., along the secant lines of the inner or outer circle of the ring) and communicate with or lead toward the inner surface of the ring from the opening 51 on the outer circumference of the ring. For haptic 43 (the upper haptic in the illustration), holes 52, 53 are blind holes that communicate with elongated cavities 54, 55 in the body of the ring between the front and rear surfaces of the ring, without communicating with either the front or rear surface of the ring, or terminating in a recess on the rear surface of the ring as in Figure 7. The elongated cavities are formed to be of a size and size that allows the haptic distal tip 16T to move parallel within the elongated cavities, while each distal tip and entry point is configured so that the tip cannot be withdrawn from the cavities. For the haptic 46 (the lower haptic in the diagram), the holes 49 and 50 are through holes that communicate with the openings 56 and 57 in the inner wall of the ring, and the lumen of each hole is preferably (in this embodiment) located between the front and rear surfaces of the ring without communicating with either the front or rear surface of the ring.

[0068] In this configuration, both ends 44,45 of the haptic can be pushed inward by the surrounding tissue, as in the previous figure, so that the haptic is less likely to damage the surrounding tissue of the ciliary groove. Also, the chordal-oriented hole, in which the tip moves parallel internally, provides a longer stroke relative to the distal tip. In the configuration in which the distal tip extends into the central opening, the stroke of the distal tip is limited to the vicinity of the inner wall of the ring and does not protrude as far into the central opening (compared to the radially oriented through hole in Figure 3).

[0069] Figure 10 also shows a configuration of a drug delivery structure 58 extending around the entire circumference of the rear surface of the ring 15, which can also be applied to the devices shown in Figures 3-9, 11-14 and 21-27. In other embodiments, the drug delivery structure 58 extends around the entire circumference of the front surface of the ring 15, which can also be applied to the devices shown in Figures 3-9, 11-14 and 21-27.

[0070] Each of the devices described above can obtain the advantage of trapping the distal haptic end within the through-hole, with or without the advantage of an exposed gripping feature that facilitates implant removal. The distal haptic tip 16T, having a larger cross-section than the remainder of the haptic ends 16d, 41, 42, 44, 45, can function as a locking means to prevent or deter the second haptic end from being fully withdrawn during implantation. The holes 18, 49, 50, 52, 53 have lumens with a smaller cross-section than the distal haptic tip 16T, so that the distal tip and distal end can slide inward or spread outward to adapt to the forces applied by the ciliary groove tissue, but remain confined within the hole so as not to escape from it.

[0071] Furthermore, this specification provides intraocular implants that may have one or more aqueous humor drainage holes as described herein. In some embodiments, such devices are ciliary sulcus implants. Figures 11 and 12 are front views of a ciliary sulcus implant / drug delivery platform. The implant may have one or more aqueous humor drainage holes 18 and may be configured for use in the ciliary sulcus of the eye. The ciliary sulcus implant / drug delivery platform comprises a preferably washer-flat ring 15 having a planar front surface 15A and a rear surface 15P and a central opening 17. A drug delivery structure is shown positioned within the ring 27. Any suitable form of haptic may be fixed to the outer edge of the drug delivery platform. The ring 15 is provided with several aqueous humor through-holes 18, which communicate between openings 20 located near the outer circumference or outer wall of the ring, or openings 19 on the outer circumference or outer wall of the ring, between the inner surface or inner wall of the ring, and near the inner wall of the ring, or near the front surface of the ring near the inner edge if the inner peripheral edge zone of the front surface is not closed by the iris after placement. If the implant is equipped with a ciliary sulcus lens or ICL, the inner openings 20 may also open to the front surface of the lens in the outer peripheral region of the lens (outside the line of sight). The ring may have a rectangular radial cross-section (square or rectangular toroid) due to its flat outer wall, flat inner wall, and flat front and rear surfaces, but one or more surfaces may be rounded, or the ring may have a circular or elliptical cross-section (torus).

[0072] Figure 12 is a front perspective view of the drug delivery platform of Figure 11, showing through-holes 18 between the outer and inner sides. Although the through-holes are shown as radially oriented, they do not need to be strictly radially oriented as long as they communicate from the ciliary sulcus to the opening of the iris, allowing for the flow of aqueous humor from the ciliary sulcus and into the anterior chamber. The through-holes may be aligned chord-wise along the secants of the ring, and they do not need to be linear. They may provide any form of fluid passages communicating from the outer side of the ring and the ciliary sulcus (when implanted) to the inner side of the ring and the pupil (when implanted). The fluid passages may comprise a mesh-like open-cell foam configured to form a reticular structure of connected open pores, in which case the ring is partially or entirely composed of the mesh-like open-cell foam. The fluid passages may also be provided by a wicking material such as wicking silicone, mesh material or fibrous material, or a hydrophilic polymer (hydrogel), which constitutes all or part of the ring.

[0073] For an implant intended as a drug delivery platform, the drug delivery structure 27 may be positioned on the rear surface of a ring, as shown in Figures 12 and 13. The ring shown in Figure 12 may instead be described, in relation to Figure 13, as a rear ring 15P and a front ring 15A connected by a plurality of web members or walls 60. The plurality of web members or walls 60 separate a plurality of channels 61, which are surrounded by webbing on both sides of the channel and a front ring and a rear ring on the front and rear boundaries of the channel.

[0074] Figure 14 shows a ciliary groove lens 62 modified by aqueous humor through-holes 18 that extend from the outer circumferential surface or wall of the lens. The through-holes communicate from an opening 19 on the outer edge or circumferential surface of the lens to a front opening 20 on the front surface of the lens itself. The front opening 20 is preferably located in the inner surface region 63 of the front surface that is not covered by the iris when the iris expands and contracts after implantation, as opposed to the outer region 64 of the front surface that is expected to be covered by the iris, but preferably well outside the optical axis and field of view 65 that is perceptible to the object. As in the previous figures, the fluid passage may consist of through-holes as shown, or it may consist of a network of open-cell foam, wicking material, mesh material or fibrous material or hydrophilic polymer (hydrogel) that constitutes all or part of the inner surface region 63.

[0075] The aqueous humor flow features described in Figures 11-14 may be incorporated into other ophthalmic implants, such as a simple ring or scaffold for supporting a drug depot, an artificial iris, a ring with an occluder paddle, an intraocular pressure sensor ring, an optical mask, or an IOL configured for implantation in the posterior chamber and ciliary sulcus or lens capsule, as shown in Figure 14.

[0076] The use of a through-hole with an exit on the front surface of the lens can be applied to other ciliary sulcus implants where the central region of the implant is occupied by a device such as an occluder or optical mask.

[0077] The drug delivery structure may be arranged as shown in Figure 11, but may also be arranged around the ring, for example, radially aligned, or close to the haptic base and haptic opening, or around the entire circumference of the rear surface of the ring. The drug delivery structure can also function as a structural element to increase the stability / rigidity of the very thin silicone, and may be arranged to enhance the silicone ring's ability to maintain its circular shape (i.e., to minimize deformation from its unconstrained circular form and avoid or minimize "ellipsification" after implantation).

[0078] Figure 15 is a front view of a ciliary sulcus implant / drug delivery platform as generally illustrated in Figure 2. Such embodiments of the ciliary sulcus implant and / or drug delivery platform may comprise at least one, preferably two or more, drug delivery structures 70, each preferably arched, having a planar front surface 70A and a rear surface (not shown in Figure 15). The drug delivery structures 70 are connected by a biasing member 71, leaving a central opening 17 defined by the inner surfaces of the drug delivery structures and the biasing member. The outer contour 70C of the drug delivery structure is preferably arched, more preferably circular, and is sized to conform to the inner curvature / circumference of the ciliary sulcus of the eye, where it is positioned when biased against the inner circumferential region of the ciliary sulcus, such as the ciliary body and ciliary projection. The biasing member is configured to fit under the iris outside the optical field of view.

[0079] Figure 16 shows the drug delivery platform of Figure 15 in a compressed form. The device can be compressed toward the compressed small-diameter form shown in Figure 16, or expand toward the open, larger, unconstrained large-diameter form of Figure 15. The device can be compressed and folded within the injector for intraocular delivery, released within the eye, and allowed to elastically expand until its outer contour contacts the ciliary sulcus, or (depending on the initial state of the device) compressed to fit the drug delivery structure 70 within the ciliary sulcus.

[0080] The biasing member can be provided in various forms. In one example, as shown in Figures 15 and 16, each biasing member includes a separate compression spring connecting the two drug delivery structures shown. Figure 17 shows a drug delivery platform 72 in which a biasing member is integrally formed with the drug delivery structure. The biasing member in this device comprises an outward expansion region 73 of the device positioned between drug depot regions 74 (however, the entire device may comprise a drug depot configured to elute or otherwise deliver a therapeutic agent). A central opening 17 is formed within the device. The expansion region is configured as a living hinge joint defined by a notch 75 and is elastically biased to open the device into the large-diameter, unconstrained form shown in Figure 17. In this form, the hinge joint is elastically open to bias the drug depot regions apart from each other, but is elastically compressible into the closed, small-diameter, constrained form shown in Figure 18. The device may be compressed and folded into an injector for intraocular delivery, released into the eye, and allowed to elastically expand until its outer contour contacts the ciliary sulcus, or (depending on the initial state of the device) compressed to fit the drug depot regions 74 into the ciliary sulcus.

[0081] Figure 18 shows the drug delivery platform of Figure 17 in a compressed form. The device can be compressed toward the compressed small-diameter form shown in Figure 18, or expand toward the open, larger, unconstrained large-diameter form of Figure 17. The device can be compressed and folded within the injector for intraocular delivery, released within the eye, and allowed to elastically expand until the outer contour contacts the ciliary sulcus, or (depending on the initial state of the device) compressed to fit the drug depot area 74 into the ciliary sulcus.

[0082] In some embodiments, the arc-shaped drug delivery structures 70 shown in Figures 15–18 are configured to engage with the equator or lateral edge of the ciliary sulcus, while the biasing members 71 are configured to bias the arc-shaped drug delivery structures 70 and maintain the ciliary sulcus implant / drug delivery platform centered with respect to the optical axis 10 of the eye (as shown in Figure 2). The arc-shaped drug delivery structures 70 may have a limited circumferential range so that they do not substantially obstruct the aqueous humor flow path. The biasing members are preferably thin in the anterior-posterior direction so that they do not substantially obstruct the aqueous humor flow path, but so that the aqueous humor can flow from the ciliary sulcus through the biasing members into the anterior chamber.

[0083] The devices of this disclosure, for example those shown in Figures 15 to 18, may be symmetrical in configuration with two drug delivery structures or drug depot areas, but these devices may be configured with asymmetrically distributed drug delivery structures or drug depot areas, and the devices may consist of one or more drug delivery structures or drug depot areas.

[0084] Several embodiments provided herein (such as those shown in Figures 15–18) are drug delivery intraocular implants comprising one or more outwardly biased drug depots. In some cases, such drug delivery intraocular implants are drug delivery ciliary sulcus implants for implantation in the ciliary sulcus or lens capsule of a target (e.g., human) eye.

[0085] Figure 19 shows a drug delivery platform having only a single arc-shaped drug delivery structure 70 with an arc-shaped outer contour 70C, similar to the drug delivery structure in Figure 15, for example. A biasing member 71, connected by an arc-shaped connector 76 (which itself is elastic and may function as part of a biasing member), is operable to elastically bias the single arc-shaped drug delivery structure 70 away from the arc-shaped connector 76. The arc-shaped drug delivery structure 70, coupled with the biasing member 71 and the arc-shaped connector 76, forms an inner opening 17. The device may also be embedded in a lens capsule, in which case the drug delivery platform in the figure is inserted into the lens capsule and allowed to elastically expand within the lens capsule until the drug delivery structure and, where applicable, the biasing member 71 or the arc-shaped connector 76 abut against the inside of the lens capsule.

[0086] Figure 20 shows a drug delivery platform comprising a drug delivery device having an elastically expandable and compressible wire frame 80, where a single drug delivery device comprises panels 81, 82 connected by columns 83, with an opening between the panels and columns, within which a portion of the compressible wire frame is positioned. The wire frame may include any suitable flexible material, such as a compressible polymer or a compressible metal.

[0087] Figures 21 and 22 show a drug delivery platform comprising a drug delivery device having an elastically expandable and compressible ring 84, to which the drug delivery structure 27 is fixed. Similar to the device in the previous figure, the device may be compressed and folded into an injector for intraocular delivery, released into the eye, and allowed to elastically expand until its outer contour contacts the ciliary sulcus, or (depending on the initial state of the device) compressed to fit the drug delivery structure 27 (e.g., a delivery depot) into the ciliary sulcus. The compressible ring 84 may be formed as a drug delivery depot, but in certain embodiments, its purpose is to bias the drug delivery structure 27 (e.g., a drug depot) outward. Figure 22 shows the compression of the device shown in Figure 21 such that the device takes on an oval shape.

[0088] Figures 23–26 show additional forms of drug delivery platforms having a flexible shape that allows for optimal device fitting within the ciliary sulcus or lens capsule while minimizing or eliminating undesirable interactions with other tissues of the eye. The individual features in Figures 23–25 may also be applied to any of Figures 3–22, 26, and 27. The drug delivery platform may comprise a ring (as shown in Figures 23–25) or partial ring (as shown in Figure 26) 15, which may be flat as a washer, having a planar front surface 15A and a planar rear surface (not shown in Figures 23–26) and a central opening 17. In other embodiments, the front surface 15A or rear surface may not be planar and may have a rounded apex or other suitable shape. In Figure 23, a closed-loop haptic 16C is attached to a haptic base 16B. In Figure 26, two closed-loop haptics 16C are attached to a haptic base 16B.

[0089] The closed-loop haptic 16C may have an hourglass shape (similar to the upper haptic in Figures 23, 24, and 25) or other suitable shapes to facilitate stabilization of the drug delivery structure and protection from damage to ocular tissue when implanted in the target eye. The drug delivery device may have a single closed-loop haptic or multiple closed-loop haptics. In other embodiments, additional haptics may also be attached to the ring. As shown in Figures 23 and 24, a second set of haptics (reference numeral 16A in Figure 23 and reference numeral 16U in Figure 24) can be attached to the ring 15 at the haptic base 16B. These additional haptics may take various forms, including a U-shape (similar to the lower haptic in Figure 24), an A-shape (similar to the lower haptic in Figure 23), or other suitable shapes as shown in Figures 3 to 10. Each of the closed-loop haptic and the other haptics 16A, 16U may be attached at the haptic base 16B by any suitable method including mechanically fixing the haptic to the ring, overmolding the haptic with the ring, fusing the haptic to the ring, attaching the haptic to the ring by heat shrink attachment, attaching the haptic to the ring by adhesive, or by any other suitable attachment. Alternatively, the closed-loop haptic 16C and / or the other haptics 16A, 16U may also be flexibly connected to the ring 15 in any of the methods described with respect to Figures 3 to 10.

[0090] As shown in Figure 24, the haptic 16U can also pass through a through-hole or channel 84 of the ring 15 so that it extends into the central opening 17 of the device and forms a gripping feature portion 85.

[0091] As shown in Figure 25, the drug delivery device may include an extension of the ring 15 to form one or more retention feature portions 15D. The retention feature portions may be made of the same or different material as the ring. The retention feature portions 15D may be continuous with the ring or may be attached to the ring by any suitable method.

[0092] The partial ring 15 in Figure 26 is compressible under applied force. The result of such compression on the device is shown by dashed lines in Figure 26. Like other devices in this disclosure, the devices in Figures 23–26 may include a drug delivery structure, which may be located on the front 15A or rear surface, incorporated into a ring, or located in a separate compartment within the device.

[0093] The device in Figure 27 comprises a flexible and compressible ring structure 86 that forms a central opening 17. The device also includes one or more drug delivery structures 27 (attached to the ring structure at the base 87 of the ring structure), a loop 71a that facilitates the stabilization of the ring structure, and a biasing member 71 positioned between the drug delivery structures 27. The ring structure may be made of the same material as that found in any of the haptics described herein.

[0094] In various embodiments of this disclosure, the haptics 16L, 16, 16C, 16A, 16U are connected to the ring or partial ring 15, 83, 86 by mechanically fixing the haptics to the ring or partial ring, overmolding the haptics with the ring or partial ring, fusing the haptics to the ring or partial ring, attaching the haptics to the ring or partial ring by heat shrink attachment, attaching the haptics to the ring or partial ring by adhesive, or by any other suitable attachment. Such attachments include those shown in Figures 3 to 9 and Figures 23 to 26.

[0095] Suitable materials for the haptics 16L, 16, 16C, 16A, 16U, 43, and 46 of this disclosure include biocompatible materials, such as polymer materials including polymethyl methacrylate (PMMA), polyvinylidene fluoride (PVDF), polypropylene (PP), and polyethersulfone (PES), or any combination thereof. Suitable materials for the rings or partial rings 15, 83, and 86 of this disclosure include biocompatible materials, such as polymer materials including silicone, acrylic resin, hydroxyethyl methacrylate (HEMA), polyethyl methacrylate (PEMA), polyethyl acrylate (PEA), and combinations thereof.

[0096] In various embodiments, the ophthalmic implant of the present disclosure comprises a ring or partial ring 15 comprising a first material and configured for implantation in a target eye, characterized by an outer surface, an inner wall, and a central opening 17; and closed-loop haptics 16, 16C, 16L, 43, 46 comprising a second material and attached to the ring or partial ring at first haptic ends 16d, 41, 45 and second haptic ends 16d, 42, 44. The first and second materials have different chemical compositions, and the ring or partial ring is more rigid than the closed-loop haptics.

[0097] In various embodiments, the forces applied to the ophthalmic implants of this disclosure (e.g., those shown in Figures 3-10 and 23-26) are sufficient to deform the haptics (e.g., closed-loop haptics 16, 16C, 16L, 43, 46), but not the rings or partial rings. Generally, under the conditions present in the eye after implantation, the rings or partial rings retain their shape, while the closed-loop haptics deform. In some embodiments, with an applied force of 100 mN, the rings or partial rings retain their shape, and the closed-loop haptics deform. In other embodiments, with an applied force of 80 mN, the rings or partial rings retain their shape, and the closed-loop haptics deform. In yet another embodiment, with an applied force of 60 mN, the rings or partial rings retain their shape, and the closed-loop haptics deform. In yet another embodiment, with an applied force of 50 mN, the rings or partial rings retain their shape, and the closed-loop haptics deform. In some embodiments, with an applied force of 40 mN, the ring or partial ring maintains its shape, while the closed-loop haptic deforms. In yet another embodiment, with an applied force of 30 mN, the ring or partial ring maintains its shape, while the closed-loop haptic deforms. In yet another embodiment, with an applied force of 20 mN, the ring or partial ring maintains its shape, while the closed-loop haptic deforms. In yet another embodiment, with an applied force of 10 mN, the ring or partial ring maintains its shape, while the closed-loop haptic deforms. In some embodiments, with an applied force of 5 mN, the ring or partial ring maintains its shape, while the closed-loop haptic deforms.

[0098] The drug delivery devices shown in Figures 3 to 27 may be configured in various ways to facilitate the delivery of therapeutic drugs to ocular tissues. Generally, as further described herein, one or more drug delivery structures 27, 58, 70, 81 may be provided as drug depots or drug masses in the form of blocks, plates, wafers, etc., containing a therapeutic drug or a therapeutic drug placed in a matrix, or they may contain an erosive therapeutic drug or a therapeutic drug in a matrix forming a drug-eluting structure. Each of the devices described herein for implantation in the posterior chamber and ciliary sulcus is also suitable for implantation in the lens capsule. The devices of this disclosure are configured to deliver a therapeutic drug to the lens capsule at the equator of the lens capsule or to the posterior chamber and ciliary sulcus. For example, the therapeutic drug may function to suppress the proliferation and activity of lens endothelial cells and the development of posterior capsular opacification (e.g., cytoskeletal drugs, latruncrine, anti-VEGF, etc.).

[0099] For each of the devices described herein and shown in Figures 3 to 27, the drug delivery structures 27, 58, 70, 81 may be located on or within the rear surface 15P, on or within the front surface 15A, or in combination thereof. The drug delivery structures may be fixed directly to the rear and / or front surface, located in a compartment fixed to the rear surface, or incorporated into the device in other ways. The rings or partial rings 15, 83, 86 themselves may include drug delivery structures 27, 58, 70, 81 composed of, for example, a therapeutic agent in a silicone matrix.

[0100] II. Methods for implanting and manipulating ophthalmic implants The intraocular implants of this disclosure, as shown in Figures 3 to 27, can be used for a variety of purposes in the target eye. In some embodiments, the drug delivery platform of such devices described herein can be used to deliver a therapeutic agent intraocularly into the ciliary sulcus of the target eye. In various embodiments, the drug delivery devices of this disclosure comprise a closed-loop haptic, or more specifically, a U-loop haptic. Using various embodiments of this disclosure, a surgeon can insert the drug delivery device of this disclosure into the target eye, position the haptic under the iris, and center the ring relative to the lens capsule and lens.

[0101] In some embodiments, the devices of the present disclosure include an IOL. For example, such a device with an IOL is shown in Figures 7 and 8, or for the devices shown in Figures 3–6, 10–14, and 23–25, and is shown as an IOL located within a central opening 17 of the present disclosure and surrounded by an optional ring 15. In various embodiments, the devices of the present disclosure can be implanted in an eye of a subject in which the IOL device has been previously implanted (for example, as a device implanted in the lens capsule), or in an eye of a subject that still contains a natural lens and has an intact lens capsule.

[0102] The devices of this disclosure, as shown in Figures 3 to 27, can be implanted such that the device is centered on or not centered on the optical axis of the eye. Subsequently, either during surgery or considerably after implantation, the surgeon may remove the drug delivery platform by inserting a tip-grasping instrument into the eye through the incision (at the base of the cornea, the “clear cornea” or “limbic entry point” along the limbus, or even the “scleral entry point”), for example, a Sinskey hook or micro-grasping forceps, under the cornea from a point opposite the tip to be grasped, or from an entry point circumferentially displaced from the tip to be grasped (around the edge of the cornea), thereby the instrument pulls the tip radially inward, then grasps the tip, and gently pulls the tip radially inward across the opening, disengaging the haptic from the ciliary sulcus and moving it to a position anterior to the iris, and repeating this process from the other side of the cornea (the other side of the limbus (the boundary between the cornea and the sclera) or the other side of the anterior chamber) to release a second haptic tip, thereby removing the drug delivery platform through the incision under the cornea. This removal procedure can be performed without inserting an instrument into the ciliary groove, or grasping and directly manipulating the loop portion of the haptic, or exposing the iris to the tip of the haptic, or exposing the tip of the haptic into the ciliary groove.

[0103] While drug delivery platforms are described, the modified haptic structures shown in Figures 3-10 and 23-26 above may be incorporated into other ophthalmic implants, including simple rings or scaffolds for supporting drug depots, artificial irises, rings with occluder paddles, intraocular pressure sensing rings, optical masks, etc., or IOLs configured for implantation in the posterior chamber and ciliary sulcus, as shown in Figures 7 and 8. Furthermore, devices described for implantation in the posterior chamber and ciliary sulcus may also be implanted in the lens capsule to obtain, in combination or alone, the advantages of a captured haptic, or a form of stress relief by capturing the haptic in a hole, or the advantages of grasping the haptic tip for adjustment and removal.

[0104] In various embodiments of this disclosure, the haptic tip 16T may preferably be configured to facilitate engagement with a Sinski hook, micro-gripping forceps, or other instrument. In addition to the haptic tip 16T incorporating a gripping feature 21, additional devices of this disclosure incorporate a gripping feature 85. As shown in Figures 3, 5, 6, 10, and 24, the haptic tip 16T may be composed of gripping features 21, 85 such as eyelets, or other forms such as pinholes (formed to accommodate a Sinski hook), arbitrary serrations, flanges, hooks, wrench flats, or other planes that can be gripped by micro-gripping forceps. For the devices shown in Figures 3 to 10, if other suitable gripping instruments are available, or if the operations described below are not anticipated, the tip may be terminated at a blunt end without a gripping feature. Without requiring insertion of the instrument into the ciliary sulcus or posterior chamber, the haptic can be detached from the ciliary sulcus position without engaging with the iris or surrounding tissue, lifted above the mounting plane for easier removal, and thus minimize trauma to associated tissue. These haptics 16L, 16, 16C, 16A, 16U, 43, 46 (including haptic loops 16L, 16, 16C, 43, 46) can also assist in positioning the device during initial implantation, such that the haptic can be brought together (towards the geometric center of the entire device) and then released (allowed to open into the ciliary sulcus) when the ring is properly positioned. In various embodiments, the constrained nature of the haptic (closed-loop haptic of this disclosure) will also make it easier to fold the device for insertion into the eye, and its reproducibility will also be increased. This is because the haptic is constrained in a known space and axis, and therefore it will be easier to compress the device into the injector and then inject or place it into the eye.

[0105] III. Methods of treating the subject using ophthalmic implants The drug delivery devices of the present disclosure, as shown in Figures 3 to 27, may be used to deliver therapeutic drugs intraocularly to a target eye, including the ciliary sulcus or lens capsule. For example, for the treatment of glaucoma, the therapeutic drug in the drug delivery structure 27, 58, 81 may be a therapeutic drug effective in reducing intraocular pressure, such as bimatoprost. In some embodiments, a surgeon inserts one of the devices of the present disclosure (e.g., as shown in Figures 3 to 27) into the posterior chamber located between the iris and the lens capsule, with the anterior surface facing the iris and the posterior surface facing the lens capsule, and any haptic used extending into the ciliary sulcus.

[0106] In each of the embodiments described herein, including those shown in Figures 3 to 27, the drug delivery device may be configured to deliver a variety of therapeutic drugs for treating a condition or disease of a subject requiring treatment. Treatment includes any recovery of the condition or disease, or any improvement (subjective or objective) of any of these symptoms. The devices of this disclosure can be used to treat age-related macular degeneration, amblyopia, cataracts, color blindness, diabetic retinopathy, dry eye, floaters, glaucoma, conjunctivitis, refractive errors, retinal detachment, and any combination thereof. In some embodiments, therapeutic drugs may include bimatoprost, brimonidine, latanoprost, timolol, pilocarpine, brinzolamide, as well as other drugs in the general category of beta-blockers, alpha-agonists, Rho-kinase (ROCK) inhibitors, adenosine receptor agonists, carbonic anhydrase inhibitors, adrenergic and cholinergic receptor activators, and prostaglandin analogs, which may be incorporated into the drug delivery device to treat glaucoma. Aflibercept, bevacizumab, pegaptanib, ranibizumab, steroids, and aptamers can be incorporated into drug delivery devices to treat exudative macular degeneration. Complement factors, antioxidants, and anti-inflammatory drugs can be incorporated into drug delivery devices to treat atrophic macular degeneration. Methotrexate, antibodies, dexamethasone, triamcinolone, and other steroids can be incorporated into drug delivery devices to treat uveitis. Antiproliferative agents, antimitotic agents, anti-inflammatory drugs, and other agents that inhibit the diffusion of lens epithelial cells can be incorporated into drug delivery devices to treat posterior capsule opacity. Antibiotics such as fluoroquinolones, nonsteroidal drugs such as ketorolac, and steroids such as prednisolones can be incorporated into drug delivery devices to treat infection and inflammation for postoperative management after cataract surgery.

[0107] This specification further provides a method of treating a subject using a drug delivery intraocular implant comprising an outwardly biased drug depot, as shown, for example, in Figures 21, 22, and 27. Further embodiments of this disclosure (e.g., any of Figures 3–20 and 23–26) can be modified to comprise one or more outwardly biased drug depots. As disclosed herein, such a drug delivery intraocular implant is a drug delivery ciliary sulcus implant for implantation in the ciliary sulcus or lens capsule of the subject eye. In various embodiments, when in use, a ciliary sulcus implant and / or drug delivery platform (or other embodiments modified to incorporate a drug depot), such as those shown in Figures 21, 22, and 27 herein, comprising an outwardly biased drug depot, can be used to deliver a therapeutic agent intraocularly to the subject eye by inserting the drug delivery structure into the ciliary sulcus, inserting the device into the anterior chamber, and elastically expanding the device. When released into the anterior chamber, the biasing member elastically expands circumferentially, pushing the drug delivery structures outward within the ciliary sulcus until they abut against anatomical structures at the ciliary sulcus angle.

[0108] This specification provides a method for using an intraocular implant that includes one or more aqueous humor flow holes (e.g., as shown in Figures 11-14, or as incorporated in any of Figures 3-10 and 15-17). In various cases, such an implant is a ciliary sulcus implant for implantation in the ciliary sulcus or lens capsule of the eye in question. After implantation, the fluid passage allows aqueous humor to pass through the ring and prevents fluid from accumulating in the ciliary sulcus and posterior chamber. When implanted in the lens capsule such that the passage allows fluid flow from the inner wall of the ring to an opening 19 adjacent to the circumferential surface of the ring, the therapeutic agent can be delivered from the central opening to the equator of the lens capsule.

[0109] Preferred embodiments of the devices and methods are described in relation to the environment in which they were developed, but these embodiments are merely illustrative of the principles of the present invention. Elements of various embodiments can be incorporated into each of other types to obtain the advantages of these elements combined with such other types, and various beneficial features can be utilized individually or in combination with each other in embodiments. Other embodiments and forms can be devised without departing from the spirit of the present invention and the scope of the appended claims.

Claims

1. It is an ophthalmic implant, A ring or partial ring (15) comprising a first material and configured for implantation in the target eye, characterized by an outer surface, an inner wall, and a central opening (17), A haptic (16, 16C, 16L, 43, 46) comprising a second material and attached to the ring or partial ring at the first haptic ends (16d, 41, 45), The first material and the second material have different chemical compositions, and one of the ring or partial ring and the haptic is more rigid than the other. An ophthalmic implant further comprising at least one drug delivery structure (70) disposed within the ring or partial ring (15) and containing a polymer matrix and a therapeutic agent disposed therein.

2. The ophthalmic implant according to claim 1, wherein, under conditions present in the eye after implantation, the ring or partial ring maintains its shape, and the haptic deforms.

3. An ophthalmic implant according to claim 1 or 2, wherein, upon application of a force of 100 mN, the ring or partial ring maintains its shape and the haptic deforms.

4. An ophthalmic implant according to claim 1 or 2, wherein with an applied force of 10 mN, the ring or partial ring maintains its shape and the haptic deforms.

5. An ophthalmic implant according to any one of claims 1 to 4, comprising multiple haptics.

6. The ophthalmic implant according to any one of claims 1 to 5, wherein the first haptic end is flexibly connected to the ring at the first haptic end such that the haptic can be deformed by a force applied by the tissue in which the implant is embedded.

7. An ophthalmic implant according to any one of claims 1 to 6, wherein a portion of the haptic passes through the holes (18, 49, 50, 84) of the ring and enters the central opening to form a gripping feature portion (21, 85).

8. The haptic is a closed-loop haptic and has a second haptic end, The ophthalmic implant according to any one of claims 1 to 7, wherein the second haptic end is flexibly connected to the ring at the second haptic end such that the closed-loop haptic is deformable by a force applied by the tissue in which the implant is embedded.

9. The ophthalmic implant according to claim 8, wherein the closed-loop haptic is configured such that the first haptic end, the second haptic end, or a combination thereof is positioned within the recess of the ring (15).

10. The ophthalmic implant according to any one of claims 1 to 5 or 7 to 9, wherein the first haptic end is attached to the ring by mechanically fixing the first haptic end to the ring, overmolding the first haptic end with the ring, fusing the first haptic end to the ring, attaching the first haptic end to the ring by heat shrink attachment, attaching the first haptic end to the ring with adhesive, or a combination thereof.

11. The ophthalmic implant according to claim 8 or 9, wherein the second haptic end is attached to the ring by mechanically fixing the second haptic end to the ring, overmolding the second haptic end with the ring, fusing the second haptic end to the ring, attaching the second haptic end to the ring by heat shrink attachment, attaching the second haptic end to the ring with adhesive, or a combination thereof.

12. The ophthalmic implant according to any one of claims 1 to 11, wherein the first material is a biocompatible material and the second material is a biocompatible material.

13. An ophthalmic implant according to any one of claims 1 to 12, wherein the first material is a first polymer and the second material is a second polymer.

14. The ophthalmic implant according to any one of claims 1 to 13, wherein the first material is selected from the group consisting of silicone, acrylic resin, hydroxyethyl methacrylate (HEMA), polyethyl methacrylate (PEMA), and polyethyl acrylate (PEA), or any combination thereof.

15. The ophthalmic implant according to any one of claims 1 to 14, wherein the second material is an elastomer.

16. The ophthalmic implant according to any one of claims 1 to 15, wherein the second material is selected from the group consisting of polymethyl methacrylate (PMMA), polyvinylidene fluoride (PVDF), polypropylene (PP), and polyethersulfone (PES), or any combination thereof.

17. The ophthalmic implant according to any one of claims 1 to 16, further comprising a lens (34) disposed within the central opening (17).

18. The ophthalmic implant according to any one of claims 1 to 17, wherein the polymer matrix is ​​bioerosive.

19. The ophthalmic implant according to any one of claims 1 to 18, wherein the therapeutic agent comprises one or more of the following: a prostaglandin analog, an alpha agonist, a Rho-kinase (ROCK) inhibitor, an adenosine receptor agonist, a carbonic anhydrase inhibitor, an adrenergic and / or cholinergic receptor activator, a steroid, an aptamer, a complement factor, an antioxidant, an anti-inflammatory agent, an antibody, an antiproliferative agent, an antimitotic agent, or an anti-inflammatory agent.

20. The ophthalmic implant according to claim 19, wherein the prostaglandin analog comprises bimatoprost.

21. The ophthalmic implant according to claim 1, wherein the ring or partial ring has higher rigidity than the haptic.

22. The ophthalmic implant according to claim 1, wherein the haptic has higher rigidity than the ring or partial ring.

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