US 2005O244462A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0244462 A1 Farooq (43) Pub. Date: Nov. 3, 2005 (54) DEVICES AND METHODS FOR TREATING A (57) ABSTRACT MAMMALIAN EYE (75) Inventor: Sidiq Farooq, Newark, CA (US) Devices and methods for delivering a therapeutically active ocular implant into an eye are provided. Such a device Correspondence Address: generally includes a hollow sleeve having an open proximal STOUT, UXA, BUYAN & MULLINS LLP end, a distal end, a Substantially uniform inner diameter and 4 VENTURE, SUITE 300 a Substantially uniform outer diameter extending between IRVINE, CA 92618 (US) the proximal end and the open distal end. In addition, the device includes a plunger element having an angled con (73) ASSignee: Allergan, Inc., Irvine, CA figuration and sized to be slidably received within the sleeve for urging an implant from the distal end of the sleeve and (21) Appl. No.: 10/836,908 into an eye. Systems for performing ocular research are (22) Filed: Apr. 30, 2004 provided which include a plurality of such hollow sleeves cut from a Single flouroplastic tube, and a plurality of Publication Classification plunger elements cut from a Single wire. The devices, Systems and methods are especially useful for facilitating (51) Int. Cl. ................................................... A61F 2/00 implantation of relatively fragile, for example brittle, ocular (52) ... 424/427 implants in an intact condition. Patent Application Publication Nov. 3, 2005 Sheet 1 of 2 US 2005/0244462 A1 FIG. 1 1OO 112 112 ". 114 S. T 114 142 116 116 142 142 FIG. 2 Patent Application Publication Nov. 3, 2005 Sheet 2 of 2 US 2005/0244462 A1 3OO 530 346 28 326 334 FIG. 3 US 2005/0244462 A1 Nov. 3, 2005 DEVICES AND METHODS FOR TREATING A and describes implanting microcapsules comprising hydro MAMMALIAN EYE cortisone Succinate into the posterior Segment of the eye. 0009 Wong, U.S. Pat. No. 5,164,188 discloses encapsu BACKGROUND lated agents for introduction into the Suprachoroid of the 0001. The present invention generally relates to systems eye, and describes placing microcapsules and plaques com and methods for treating eyes and more Specifically relates prising hydrocortisone into the pars plana. to Systems and methods for delivering drug delivery 0010 Wong et al., U.S. Pat. Nos. 5,443,505 and 5,766, implants into eyes, for example, mammalian eyes. 242 disclose implants comprising active agents for intro 0002 Solid pharmaceutically active implants that pro duction into a Suprachoroidal Space or an avascular region of vide controlled release, for example, Sustained release, of an the eye, and describes placing microcapsules and plaques active ingredient are able to provide a relatively uniform comprising hydrocortisone into the parS plana. concentration of active ingredients in the body. Implants are 0011 Wong et al., U.S. Pat. No. 5,869,079 discloses particularly useful for providing a high local concentration combinations of hydrophilic and hydrophobic entities in a at a particular target Site for extended periods of time. biodegradable Sustained release implant, and describes a Additionally, Sustained release forms may reduce the num polylactic acid polyglycolic acid (PLGA) copolymer ber of doses of the drug required to be effective in treatment implant comprising dexamethasone. of a condition, and often reduce the occurrence of Side 0012 Wong, U.S. Pat. No. 5,824,072 discloses implants effects and/or inconsistency in drug concentration found for introduction into a Suprachoroidal Space or an avascular with traditional drug therapies. region of the eye, and describes a methylcellulose (i.e. 0.003 Various sites exist in the eye for implantation of a non-biodegradable) implant comprising dexamethasone. drug delivery device or implant, Such as the Vitreous of the 0013 Zhou et al. disclose a multiple-drug implant com eye, anterior or posterior chambers of the eye, or other areas prising 5-fluorouridine, triamcinolone, and human recombi of the eye including intraretinal, Subretinal, intrachoroidal, nant tissue plasminogen activator for intraocular manage Suprachoroidal, intrascleral, episcleral, Subconjunctival, ment of proliferative vitreoretinopathy. Zhou, T., et al. intracorneal or epicorneal Spaces. Wherever the desired “Development of a multiple-drug delivery implant for location of implantation, typical methods of implantation all require relatively invasive Surgical procedures, pose a risk of intraocular management of proliferative vitreoretinopathy', excessive trauma to the eye, and require excessive handling Journal of Controlled Release 55: pp. 281-295. of the implant. For example, in a typical method for place 0014 Heller, “Biodegradable Polymers in Controlled ment in the Vitreous, an incision is made through the Sclera, Drug Delivery”, in: CRC Critical Reviews in Therapeutic and the implant is inserted into and deposited at the desired Drug Carrier Systems, Vol. 1, (CRC Press, Boca Raton, Fla., location in the Vitreous, using forceps or other like manual 1987), pp.39-90, describes encapsulation for controlled drug grasping device. Once deposited, the forceps (or grasping delivery. Heller, in: Hydrogels in Medicine and Pharmacy, device) is removed, and the incision is Sutured closed. N. A. Peppes ed., Vol. III, (CRC Press, Boca Raton, Fla., 1987), pp 137-149, describes bioerodible polymers. 0004. There are many drawbacks of such techniques for intraocular implant delivery. Extensive handling of the 0.015 Anderson et al., Contraception 13:375, (1976), and implant is necessitated in these techniques, creating a risk Miller et al., J. Biomed. Materials Res. 11:711, (1977) that the implant will be damaged in the process. Many Such describe various properties of poly(dL-lactic acid). implants, particularly bioerodible implants, are polymer 0016 Brine, U.S. Pat. No. 5,075,115 discloses controlled based and are relatively fragile. If portions of Such implants release formulations with lactic acid polymers and co are damaged and broken-off, the effective therapeutic dose polymers. delivered by the implant once placed will be significantly altered. In addition, it becomes inherently difficult using 0017 Di Colo, Biomaterials 13:850-856 (1992) these methods to achieve reproducible placement from describes controlled drug release from hydrophobic poly patient to patient. CS. 0005 There thus remains a need for a more convenient, 0018 Olejnik, et al. U.S. Pat. No. 6,074,661 discloses an leSS invasive, and leSS traumatic means for delivering implantable device for treatment of an eye, wherein the implants into the eye, for example, into the Vitreous of the device incorporates a retinoid for improving the biocompat eye. There also remains a need for a more controlled means ability of the device in eye tissue. of delivering implants into the eye. 0019 Wong, U.S. Pat. No. 6,699,493 discloses a method for reducing or preventing transplant rejection in the eye and 0006 The following patents and additional publications intraocular implants for use therefor. include disclosure which is relevant to and/or helpful in understanding the present invention. 0020. Other documents that are also relevant or otherwise helpful in understanding the present invention are U.S. 0007 Weber et al., U.S. patent application Ser. No. patent application Ser. No. 09/693,008, filed on Jul. 5, 2000; 10/246,884, filed on Sep. 18, 2002, having Pub. No. U.S. Ser. No. 10/327,018, filed on Dec. 20, 2002 and Ser. No. 2004/00543.74 A1, describes apparatus and methods for 10/340,237, filed on Jan. 9, 2003. delivering ocular implants into an eye of a patient. 0021. The entire disclosure of each of the documents 0008 Wong, U.S. Pat. No. 4,997,652 discloses biode cited hereinabove is incorporated herein in its entirety by gradable ocular implants, including encapsulated agents, this reference. US 2005/0244462 A1 Nov. 3, 2005 SUMMARY 0028 Preferably, the step of introducing the implant into 0022. The present invention provides new devices, sys the eye includes advancing a plunger element, for example tems and methods for placing a drug delivery implant into an a relatively thin, elongated filament or wire, into the open eye, for example, to achieve one or more desired therapeutic proximal end of the hollow sleeve and passing the plunger effects. The present apparatus and methods are useful for element through the hollow sleeve in a distal direction in placing drug delivery implants, for example, Substantially order to pass or urge the implant out of the distal end of the biodegradeable drug delivery implants, into an eye, Such that hollow sleeve. For example, the plunger element may be the implant remains Substantially intact during the place held in a relatively fixed position while the hollow sleeve is ment procedure, for example, without causing any Substan gently drawn in a proximal direction out of the eye. Thus, tial breakage or other damage to the implant. For example, the plunger element functions to hold the implant in place the devices, Systems and methods of the invention are while the hollow sleeve is withdrawn. The plunger element Suitable for use in implanting drug delivery implants that are is then gently withdrawn from the eye, thereby leaving the relatively non-flexible, rigid, fragile, and/or otherwise prone implant in place within the eye. to damage or breakage. For example, the present methods 0029. Typically, the present invention is directed toward, and Systems are highly effective in delivering an implant in but not limited to, treatment of a mammalian eye, for an intact condition into an eye wherein the implant has a example an animal or a human eye. In other aspects of the degree of brittleness that would typically contribute to invention, ocular research Systems and methods are pro breakage thereof in the event the same implant had been Vided that can be incorporated into research and testing of Subjected to a conventional Surgical implantation procedure. drug delivery implants in animal Studies.