Related Applications

[0001] The present application claims benefit under 35 U.S.C. § 119 of U.S. Patent Application No. 16/893,372, filed June 4, 2020, entitled OPHTHALMIC IMPLANT SYSTEM FOR DRUG DELIVERY”, which is incorporated herein by reference in its entirety.

Field of the Invention

[0002] The inventions described below relate to the field of ophthalmic implants such as intraocular lenses.

Background of the Invention

[0003] Intraocular lenses (lOL’s) are artificial lenses for the eye that can be implanted to replace the natural lens of a patient’s eye after the natural lens is removed. The natural lens might be removed because it is affected by cataracts, and the IOL can be implanted to provide clear vision and some degree of focusing to the patient. Intraocular lens may also be implanted in a patient without removing the natural lens (a phakic intraocular lens or PIOL), to correct extreme near-sightedness or far-sightedness. It is advantageous to administer some therapeutic agents to the eye, coincident with implantation of the IOL, to alleviate various side effects of the IOL or treat other conditions of the eye that might coexist with the conditions that lead to cataracts. Side-effects such as infection and inflammation, and conditions such as glaucoma, can be treated with therapeutic agents that may be incorporated into additional devices that may be secured to the IOL. In addition to lOL’s, ocular implants not including lenses may be implanted to address various other conditions. Kahook, et al., Ophthalmic Device For Drug Delivery, U.S. Pub. 20200022840 (January 23, 2020) (the disclosure of which is hereby incorporated in its entirety) discloses various ophthalmic implant systems, including IOL systems including IOL assemblies combined with drug delivery devices.

Summary

[0004] The devices and methods described below provide for easier placement of therapeutic agents along with ocular implants, including lOL’s. This is accomplished with an ophthalmic implant system including a first or primary device, which may be an intraocular lens assembly or other intraocular implant, and a secondary device comprising a drug delivery device. The drug delivery device is configured for attachment to the intraocular lens assembly or other intraocular implant. Attachment of the drug delivery device to the intraocular lens assembly or other intraocular implant is accomplished through releasable or non-releasable means, and may be accomplished upon manufacture of the IOL assembly, peri-operatively immediately before or after implantation, or intra-operatively, in the same procedure in the IOL assembly is implanted. The drug delivery device may be configured to allow for placement of a second drug delivery component into the first drug delivery device, and placement may be may be accomplished upon manufacture of the IOL assembly, peri- operatively immediately before or after implantation, intra-operatively, in the same procedure in the IOL assembly is implanted. The first and/or second drug delivery device may be subject to depletion, and upon deletion may be removed and replaced, in an operation that may be accomplished long after the surgery in which the IOL assembly is first inserted.

Brief Description of the Drawings

[0005] Figures 1 and 2 illustrate the environment of use of an ophthalmic implant system for drug delivery.

[0006] Figures 3A through 3D illustrate an ophthalmic implant system including an IOL assembly and a drug delivery device.

[0007] Figures 4A through 4E illustrate an ophthalmic implant system including an IOL assembly, a first drug delivery device and a second drug delivery device.

Detailed Description of the Invention

[0008] Figures 1 and 2 illustrate placement and use of an ophthalmic implant system in the eye of a patient. The eye 1 includes a lens 2 (the natural lens of the eye) and lens capsular bag 3, and the anterior chamber 4 which includes the cornea 5 and iris 6 and aqueous humour filling the space between the cornea and the iris, and a posterior chamber 7 between the iris and the capsular bag. The posterior cavity/vitreous body 8 is the large space between the lens and the retina 9. The natural lens 2 of the eye is characterized by an optical axis 10. (In the following description of the ophthalmic implant and or intraocular lens system, the terms posterior and anterior will be used in relation to the anatomy of the eye, in which the cornea is anterior and the retina is posterior.)

[0009] Figure 2 illustrates a placement of the ophthalmic implant system or intraocular lens system 11 in the eye including the intraocular lens assembly 12 and drug delivery device 30 which is implanted in the capsular bag in conjunction with an intraocular lens assembly 12. As shown in Figure 2, the drug delivery device is disposed anteriorly to the intraocular lens assembly 12, and is fitted over the intraocular lens assembly. The drug delivery device may also be placed below the iris and above the capsular bag. The capsular bag may contain the native lens, an artificial lens or no lens at all.

[0010] As shown in Figures 3A through 3D, a primary device is an ophthalmic implant system 20 which may include the IOL assembly 22, which includes a lens 24, one or more tabs 26 and one or more haptics 28, and one or more secondary devices 30. The ophthalmic implant 20 includes an anterior surface 20A and a posterior surface 20P. In other embodiments the ophthalmic implant 20 may comprise other devices such as a capsular tension ring, or a capsular scaffold for holding the secondary device in place.

[0011] The secondary device 30 is a drug delivery device configured for attachment (preferably releasable attachment) to a tab 26 which is part of the IOL assembly 22 and extends radially outwardly from the circumference of the lens portion 24 of the IOL 22. The tab 26 extends outwardly along a plane of the IOL lens 24, or a parallel plane, and preferably also extends in the radially outward direction to a distance that is less that the distance that the haptic 28 extends in its plane, which is also preferably in a plane of the IOL lens, or a parallel plane. The outward extent of the haptic 28 is long enough to impinge on the capsular bag when the system is implanted, while the radially outward extent of the drug delivery device 30, when installed on the implanted IOL, is preferably shorter than that of the haptic, so as to avoid impingement of the drug delivery device on the capsular bag in the equatorial region of the capsular bag. The tab 26 shown in Figure 3A includes a first radial portion 60, extending radially outwardly from a radially inward location (in this case, the circumferential edge of the IOL) which spans a first, small arc 61 along the circumferential edge of the IOL and also includes a second radial portion 62, extending from the first radial portion further radially outwardly and spanning a second arc 63 relative to the circumferential edge of the IOL lens 22L which is larger than the first, small arc 61 of the first radial portion.

[0012] The corresponding drug delivery device shown in Figure 3B includes a fixation portion 64 with an opening 65, e.g., a slot, apperature or compartment, extending from its radially inner surface 66, radially outwardly into the device and trough to the radially outer surface 67 (opposite the inner surface 66). The opening 65 is configured relative to the tab to receive the tab, such that the second radial portion 62 may be resiliently compressed to a first configuration for passage through the opening 65, until the second radial portion 62 of the tab extends outwardly from the opening, and resiliently returns toward the second configuration which is larger or wider than the opening, so that the tab, in conjunction with the opening, functions to secure the drug delivery device to the IOL assembly. (Conversely, the fixation portion (64) of the drug delivery device (30) may configured for resilient expansion to a first configuration to stretch over the second radial portion (62) of the tab (26) resilient return to return to a second configuration which is narrower than the second radial portion (62) of the tab (26).) The fixation portion may be configured as shown, or as a retaining ring extending posteriorly from drug delivery device, or as another form of anchor, fastener, or catch configured relative to the tab, to permit releasable attachment and detachment of the drug delivery device from the tab, without use of additional fastening elements or use of tools other than commonly used graspers and/or manipulating hooks.

The system with a drug delivery device secured to the IOL assembly is shown Figure 3C. Figure 3D illustrates the system with first drug delivery devices disposed on each of two tabs.

[0013] The drug delivery device also comprises a therapeutic agent, which may comprise the entirety of the drug delivery device, or an anterior portion 68 of the drug delivery device (such as a pad) anterior to the fixation portion 64, or may be embedded within a drug eluting matrix which may also comprise the entirety of the drug delivery device, or an anterior portion of the drug delivery device (such as a pad).

[0014] The ocular implant system may be introduced into the eye of a patient, through a small incision at the edge of the cornea, and into the capsular bag of the patient. For initial installation of the drug delivery device, the drug delivery device may be fixed to the IOL assembly prior to insertion of both into the eye, and the assembled system may be folded and passed through the incision and then released in the capsular bag. For initial installation of the drug delivery device, the drug delivery device may be fixed to the IOL assembly after insertion of the IOL into the eye, by first inserting the IOL through the incision and releasing it in the capsular bag, and then inserting the drug delivery device through the incision and manipulating the drug delivery device to slip the fixation portion over the tab and thereby fix the drug delivery device to the tab and IOL assembly. When an originally implanted first drug delivery device is depleted, either by elution or bio-erosion, a subsequent surgical procedure may be performed in which a surgeon removes the original first drug delivery device, making another incision at the border of the cornea to insert and fix a new first drug delivery device to the tab and IOL assembly using a grasping tool. The removal of the original first drug delivery device and replacement with a new first drug delivery device may be performed, for example, after the original first drug delivery device is exhausted or depleted, or whenever it is desired to replace the original first drug delivery device with a new first drug delivery device which contains a different therapeutic agent, and may be performed after the incision made to implant the first drug delivery device has healed, and thus requires making a new incision. During the surgical procedure, if necessary, the surgeon may insert a grasping tool to remove the first drug delivery device from the tab and IOL assembly, and remove it from the eye, and insert a new drug delivery device and use the grasping tool to manipulate the new drug delivery device to slip it over the tab and thereby secure it to the IOL assembly.

[0015] In the embodiment shown in the Figures 4A through 4E, the ophthalmic implant 20 includes the IOL assembly, which includes a lens 24, a tab 26 and a haptic 28, and a secondary device 30. The ophthalmic implant 20 includes an anterior surface 20A and a posterior surface 20P. In other embodiments the ophthalmic implant 20 may comprise other devices such as a capsular tension ring, or a capsular scaffold for holding the secondary device in place.

[0016] The secondary device 30 is a drug delivery device configured, as in Figures 3A through 3D, for attachment (preferably releasable attachment) to a tab 26 which is part of the IOL assembly 22 extends radially outwardly from the circumference of the lens portion 24 of the IOL 22. The tab extends outwardly along a plane of the IOL lens 24, or a parallel plane, and preferably also extends in the anterior direction to a distance that is less that the distance that the haptic 28 extends in it plane, which is also preferably in a plane of the IOL lens 24, or a parallel plane. The outward extent of the haptic is long enough to impinge on the capsular bag when the system is implanted, while the radially outward extent of the drug delivery device, when installed on the implanted IOL, is shorter than that of the haptic, so as to avoid impingement of the drug delivery device on the capsular bag in the equatorial region of the capsular bag. The tab 26 shown in Figure 4A includes a first radial portion 60, extending radially outwardly from a radially inward location (in this case, the circumferential edge of the IOL) which spans a first, small arc 61 along the circumferential edge of the IOL and also includes a second radial portion 62, extending from the first radial portion further radially outwardly and spanning a second arc 63 relative to the circumferential edge of the IOL which is larger than the first, small arc 61 of the first radial portion.

[0017] The corresponding drug delivery device shown in Figure 4B includes a fixation portion 64 with opening 65, e.g., a slot, apperature or compartment, extending from its radially inner surface 66, radially outwardly into the device, and, preferably, through to the radially outer surface 67. The opening is configured relative to the tab to receive the tab, such that the second radial portion 62 may be compressed to a first configuration for passage through the opening, until the second radial portion 62 of the tab extends outwardly from the opening, and resiliently returns toward the second configuration which is larger or wider than the opening, so that the tab, in conjunction with the opening, functions to secure the drug delivery device to the IOL assembly. (Conversely, the fixation portion (64) of the drug delivery device (71) may configured for resilient expansion to a first configuration to stretch over the second radial portion (62) of the tab (26) and resiliently return to return to a second configuration which is narrower than the second radial portion (62) of the tab (26).) The fixation portion may be configured as shown, or as a retaining ring extending posteriorly from drug delivery device, or as another form of anchor, fastener, or catch configured relative to the tab, to permit releasable attachment and detachment of the drug delivery device from the tab, without use of additional fastening elements or use of tools other than commonly used graspers and/or manipulating hooks. The system with a drug delivery device secured to the IOL assembly is shown Figure 4D. Figure 4E illustrates the system with first drug delivery devices disposed on each of two tabs.

[0018] The drug delivery device 71 of Figure 4B also comprises a compartment 72, with an opening or aperature on the radial inner surface (preferably), configured to fit a third device 73 shown in Figure 4C. The third device is a second drug delivery device, and comprises a therapeutic agent, which may comprise the entirety of the second drug delivery device. The second drug delivery device may also comprise a drug eluting matrix with the therapeutic agent embedded within a drug eluting matrix which may also comprise the entirety of the second drug delivery device.

[0019] Figure 4C illustrates a second drug delivery device 73 suitable for use with the first drug delivery device shown in Figure 4B. As shown, the second drug delivery device may be formed as a drug pad configured, relative to the compartment 72 of the first drug delivery device, for a friction fit in the compartment, or other releasable attachment means (slight detents on one component and detent recesses on the other, for example) suitable for intraocular use. In the example shown in Figures 4A through 4E, the second drug delivery device may have an inner edge 74 subtending a first arc 75 and an outer edge 76 subtending a second arc 77 smaller than the first arc, and the compartment 72 has a corresponding opening or aperature approximating the first arc which narrows to the spacing approximating the second arc, to provide a friction fit for the second drug delivery device while allowing easy insertion of the second drug delivery device into the compartment. The second drug delivery device is provide with a pin-hole 78 proximate its inner edge, which is sized to accommodate a tool suitable for engagement with the pinhole (an ophthalmic hook may be used), with which the second drug delivery device can be manipulated for extraction of a second drug delivery device from the compartment, and insertion of a second drug delivery device into the compartment. With this arrangement, the second drug delivery device may be inserted into the compartment before implantation of the IOL, immediately after insertion of the IOL in an intra-operative time frame (that is, during the course of a same surgical operation in which the IOL is inserted), inserting the second drug delivery device into the eye after the IOL and first drug delivery device are implanted and then inserting the second drug delivery device into the compartment. Also, long after the surgical operation in which the IOL is inserted, the second drug delivery device may be removed in a second surgical operation and, optionally, replaced with a new second drug delivery device, for example, when a drug eluting second drug delivery device has eluted much of the therapeutic agent which was initially embedded in the second drug delivery device. The assembled ophthalmic implant, including the IOL assembly, first drug delivery device and second drug delivery device, is illustrated in Figure 4D. Figure 4E illustrates the system with first and second drug delivery devices disposed on each of two tabs.

[0020] The ocular implant system of Figures 4A through 4E may be introduced into the eye of a patient, through a small incision at the edge of the cornea, and into the capsular bag of the patient. For initial installation of the drug delivery device, the drug delivery device may be fixed to the IOL assembly prior to insertion of both into the eye, and the assembled system may be folded and passed through the incision and then released in the capsular bag. Likewise, the second drug delivery device (the drug pad) can be secured within the first drug delivery device before or after prior to insertion of both into the eye. For initial installation of the drug delivery device, the second drug delivery device may be fixed to the first drug delivery device after insertion of the first drug delivery device into the eye, by first inserting the first drug delivery device through the incision and releasing it in the capsular bag, and then inserting the second drug delivery device through the incision and manipulating the second drug delivery device to insert it into the compartment 72 of the first drug delivery device. When a second drug delivery device is depleted, either by elution or bio-erosion, a subsequent surgical procedure may be performed in which a surgeon removed the original second drug delivery device, making another incision at the border of the cornea to insert and fix a new second drug delivery device within the compartment 72 using a grasping tool. If necessary, the surgeon may insert a grasping tool to remove the original second drug delivery device from the compartment of the first drug delivery device, and remove it from the eye, and insert a new second drug delivery device and use the grasping tool to manipulate the new second drug delivery device to slip it into the compartment and thereby secure it to the first drug delivery device.

[0021] The in vivo removal and placement (or replacement) of the second drug device may be accomplished without applying posteriorly or anteriorly directed force, and without applying a rotational force on the lens, first drug delivery device or second drug delivery device on the lens or the first drug delivery device. To remove a second drug delivery device from an implanted lens and first drug delivery device assembly, the surgeon may insert a single tool (a Sinsky hook or grasper) through the incision between the cornea and sclera on the side of the cornea opposite the first and second drug delivery device, fix the tool to the second drug delivery device, and apply radially inward pulling force to the second drug delivery device to gently pull the second drug delivery device from the compartment, and then continuing pulling the released second drug delivery device through the incision and out of the eye. The surgeon may insert a second tool into the eye, through the same incision or a second incision, to hold the lens and/or first drug delivery device in place, to avoid moving, or tensioning or compressing the lens and/or first drug delivery device relative to any adhered portion of the capsular bag.

[0022] To place a second drug delivery device in an empty compartment of an an implanted lens and first drug delivery device assembly, the surgeon may insert a second drug delivery device through the incision, the surgeon may insert a single tool (a Sinsky hook or grasper) through the incision between the cornea and sclera on the side of the cornea opposite the first drug delivery device and empty compartment, and push a second drug delivery device into the empty compartment, applying radially outward force on the second drug delivery device to gently pushd the second drug delivery device into the compartment. The surgeon may insert a second tool into the eye, through the same incision or a second incision, to hold the lens and/or first drug delivery device in place, to avoid moving, or tensioning or compressing the lens and/or first drug delivery device relative to any adhered portion of the capsular bag.

[0023] In both removal and placement of a second drug delivery device into the compartment, the surgeon may do so without moving or tensioning or compressing any component of the system relative to any adhered portion of the remnant anterior capsulr or the posterior capsule.

[0024] Because the posterior surface of the lens, and the posterior and anterior surface of the first drug delivery device become adhered to the capsular bag, which has already been weakened by the capsulorhexis, this approach has the advantage of avoiding pushing, pulling or rotating the adhered lens or first drug delivery device and risking further disruption of the capsule bag, or damaging the delicate zonules (suspensory ligaments of the lens) which attaches the capsular bag to the muscles of the ciliary body, or disrupting a well- formed PCO edge to allow passage of lens epithelial cells past the edge to cause posterior capsule opacifiction (secondary cataract). [0025] Likewise, in vivo removal and placement (or replacement) of the first drug device may be accomplished without applying posteriorly or anteriorly directed force, and without applying a rotational force on the lens or the first drug delivery device. Depending on the state of adhesion of the remnant anterior capsule (the ring of the portion of the anterior portion of the capsular bag remaining after creation of the capsule-rexis (the hole) to anterior surfaces of the lens or first drug delivery device, the surgeon may have to inject viscoelastic gel vial a canula to loosen the remant anterior capsule, while leaving any adhesion of the posterior capsule to the lens undisturbed. With the first drug delivery device un-attached from the remnant anterior capsule (whether because adhesion has not occurred, or becaue the surgeon has loosened the remnant anterior capsule), the surgeon may insert a tool (a grasper, forceps, etc.) through an incision between the cornea and sclera on the side of the cornea opposite the first drug delivery device, push the first drug delivery device radially outwardly to slip it off the tab, and fix the tool to the now detached first drug delivery device, and apply radially inward pulling force to the first drug delivery device to gently pull the first drug delivery device toward the center of the capsular bag, and continue pulling the now detached first drug delivery device through the incision and out of the eye. Removal of the first drug delivery device from a tab may be facilitated, and the necessary radially directed force may be reduced, by first inserting a cutter tool in to eye, through the incision, to cut the side elements of the fixation portion 64, or cut the anterior portion 68, either completely or partially, to loosen the fixation between the first drug delivery device and the tab.

[0026] To place a first drug delivery device in an unoccupied tab of an an implanted lens, the surgeon may insert a first drug delivery device through the incision, inserting a single tool (a grasper, forceps, etc.) through the incision between the cornea and sclera on the side of the cornea opposite the unoccupied tab, and push a first drug delivery device radially outward of the unoccupied tab, and then pull the first drug delivery device backward, radially inwardly, to slip it over the unoccupied tab, applying radially inward force on the first drug delivery device to gently pull the first drug delivery device into the unoccupied tab. The surgeon may insert a second tool into the eye, through the same incision or a second incision, to hold the lens in place, to avoid moving, or tensioning or compressing the lens to any adhered portion of the capsular bag.

[0027] Given the advantages of removal and replacement by applying radial forces only, the advantage of a first drug delivery device with a compartment configured to hold a second drug delivery device, where the compartment opens on a radially inward surface of the first drug delivery device, may be obtained with or without a fixation portion configured with an opening that opens on a radially inward surface of the first drug delivery device. Thus, the first drug delivery device may comprise any means for attachment to the lens (and may even be permanently attached to or integrally formed with the lens), and a compartment disposed anterior to the lens (when implanted) configured to accept a second drug delivery device, with an aperture that opens on a radially inward surface of the first drug delivery device.

[0028] In each embodiment described above, the drug delivery device of Figures 3A through 3D or the second drug delivery device (the drug pad) of Figures 4A through 4E can be configured to deliver various therapeutic agents to treat various conditions. Brimonidine, latanoprost, timolol, pilocarpine, brinzolamide and other drugs in the general categories of beta blockers, alpha agonists, ROCK Inhibitors, adenosine receptor agonists, carbonic anhydrase inhibitors, adrenergic and cholinergic receptor activating agents, and prostaglandin analogues may be incorporated into the drug delivery devices to treat glaucoma. Aflibercept, bevacizumab, pegaptanib, ranibizumab, steroids, and aptamers may be incorporated into the drug delivery devices to treat wet macular degeneration. Complement factors, anti-oxidants and anti-inflammatory agents may be incorporated into the drug delivery devices to treat dry macular degeneration. Methotrexate, antibodies, dexamethasone, triamcinolone, and other steroid agents may be incorporated into the drug delivery devices to treat uveitis. Anti-proliferative agents, anti-mitotic agents, antiinflammatory agents, and other medications that would inhibit the spread of lens epithelial cells may be incorporated into the drug delivery devices to treat posterior capsular opacification. Antibiotics such as fluoroquinolones, non-steroidal agents such as ketorolacs, and steroids such as prednisolones may be incorporated into the drug delivery devices for post-op management after cataract surgery include.

[0029] While the preferred embodiments of the devices and methods have been described in reference to the environment in which they were developed, they are merely illustrative of the principles of the inventions. The elements of the various embodiments may be incorporated into each of the other species to obtain the benefits of those elements in combination with such other species, and the various beneficial features may be employed in embodiments alone or in combination with each other. Other embodiments and configurations may be devised without departing from the spirit of the inventions and the scope of the appended claims.