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(12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al

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US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig. 2 Y-6 10 Fig. 1 8 2 2 (S10 Fig. 4 10 Fig. 3 Patent Application Publication May 25, 2006 Sheet 2 of 22 US 2006/0110428A1 Patent Application Publication May 25, 2006 Sheet 3 of 22 US 2006/0110428A1 1. 50 5421 52 -56 -d |-- Fig. 6 1.70 78 80 76 77 O O-N-72 79 74 Fig. 7 1.70 78 8O 76 77 79 72 74 Fig. 7A Patent Application Publication May 25, 2006 Sheet 4 of 22 US 2006/01 10428A1 -90 190 192 92 93 I 95 94 98 96 1 90 100 102 1N 1N 93- / \ As-92 \ , / N95 94 98 96 --- Patent Application Publication May 25, 2006 Sheet 5 of 22 US 2006/0110428A1 \f 22 120 124 Fig. 9 \|-in 1130 Fig.ig 10 Patent Application Publication May 25, 2006 Sheet 6 of 22 US 2006/0110428A1 140 145 M 143 142 144 Fig. 11 140 145 A1 143 147 149 N46 142 149 Patent Application Publication May 25, 2006 Sheet 7 of 22 US 2006/0110428A1 FORM RETNAL DETACHMENT 200 INSTILL BOACTIVE AGENT(S) IN SUBRETINAL SPACE Fig. 14 INSERT INSTRUMENT(S) LOCALIZE TO TARGET SITE 304 FORMRETINAL DETACHMENT 306 INSTILLBOACTIVE AGENT(S) IN SUBRETINAL SPACE REMOVE INSTRUMENT(S) 310 OPTIONALLY INUECT BIOACTIVE AGENT(S) 312 INTO VITREOUS HUMOR Fig. 15 Patent Application Publication May 25, 2006 Sheet 8 of 22 US 2006/0110428A1 ) Patent Application Publication May 25, 2006 Sheet 9 of 22 US 2006/0110428A1 Patent Application Publication May 25, 2006 Sheet 10 of 22 US 2006/0110428A1 INSTRUMENT(S)-352INSERT LOCALIZE TO 354 TARGET SITE FORM OPENING IN RETNA 356 INSTAGENT(S) BOACTIVE-38 SUBRETINALLY REMOVE 360 INSTRUMENT(S) OPTIONALLY, INJECT ONEAGENTSNTOVRGOUS-362 ORMORE BOACTIVE HUMOR Fig. 19 Patent Application Publication May 25, 2006 Sheet 11 of 22 US 2006/0110428A1 400 402 406 u1 404 A1 u1 ' ' -403 409 401 -o- 405 4O7 403 401 405 4O7 l A1 4.08 410 A1 409 407 M 4O7 411 407 Fig. 20 Patent Application Publication May 25, 2006 Sheet 12 of 22 US 2006/0110428A1 Patent Application Publication May 25, 2006 Sheet 13 of 22 (ur) Sseudou. Leue (ur) SSeuxolul euple 00700900Z00||0 Patent Application Publication May 25, 2006 Sheet 14 of 22 US 2006/0110428A1 -0-210 unn diameter -H210 un diameter Total drug load: -A-250 um diameter 210pm diameter - 1.29 ug (s.d. n/a) -%-250 um diameter 250pm diameter - 1.80 ug (s.d. inla) --360 um diameter 360pm diameter - 4.35 pig (s.d. inla) : 1.5 0.5 10 15 20 25 30 Time (Days) Fig. 24 -0-150 unm diameter -H 150 um diameter Total drug load: -A-320 unn diameter 150pm diameter - 1.50 ug (s.d. 0.06) -%-320 unm diameter 320pm diameter - 5.33 ug (s.d. 0.15) 10 15 2O 25 30 Time (Days) Fig. 25 Patent Application Publication May 25, 2006 Sheet 15 of 22 US 2006/0110428A1 -0-150 un diameter -H 150 um diameter Total drug load: -A-320 um diameter 150pum diameter - 1.96 ug (s.d. 0.86) ->e-320 um diameter 320pum diameter - 11.62 ug (s.d. 0.77) 1 2 O 5 10 15 20 25 30 Time (Days) Fig. 26 Patent Application Publication May 25, 2006 Sheet 16 of 22 US 2006/0110428A1 50pm Patent Application Publication May 25, 2006 Sheet 17 of 22 US 2006/0110428A1 Patent Application Publication May 25, 2006 Sheet 19 of 22 US 2006/0110428A1 Patent Application Publication May 25, 2006 Sheet 20 of 22 US 2006/01 10428A1 Patent Application Publication May 25, 2006 Sheet 21 of 22 US 2006/01 10428A1 s RETINAL THICKNESS Video Image RS:5 Bhate |012002 Patent Application Publication May 25, 2006 Sheet 22 of 22 US 2006/0110428A1 US 2006/01 10428 A1 May 25, 2006 METHODS AND DEVICES FOR THE TREATMENT example, is known to be a powerful angiostatic agent. Its OF OCULAR CONDITIONS systemic side effects, however, include peripheral neuropa 0001) This application claims the benefit of U.S. Provi thy, central nervous system depression, and embryotoxicity. sional Application Ser. No. 60/585,236, filed Jul. 2, 2004, In addition, these systemic side effects have limited the entitled “METHODS, DEVICES AND SYSTEMS FOR dosage administered to patients for the treatment of Subreti TREATMENT OF OCULAR DISEASES AND CONDI nal neovascularization. Systemic inhibition of angiogenesis TIONS,” and U.S. Provisional Application Ser. No. 60/669, in older patients can also interfere with the development of 701, filed Apr. 8, 2005, entitled “SUSTAINED DELIVERY collateral circulation, which has a role in the prevention of DEVICES FOR THE CHOROID AND RETINA AND central nervous system as well as cardiac ischemic events. METHODS FOR SUBRETINAL ADMINISTRATION OF 0007. A number of techniques or methodologies have BIOACTIVE AGENTS TO TREAT AND/OR PREVENT been developed to deliver drugs to the various tissues or RETINAL DISEASES,” which applications are incorpo structure that make up the mammalian eye, as described rated herein by reference in their entirety. hereinafter, to treat a wide range of disorders or diseases of the eye. However, delivery of drugs, proteins and the like to FIELD the eye(s) of mammals in order to achieve the desired therapeutic or medical effect, especially to the retina and/or 0002 The invention relates to methods and devices for the choroid, has proved to be challenging, owing in large the treatment of ocular conditions. part to the geometry, delicacy and/or behavior of the eye and its components. A brief description of various conventional BACKGROUND methods or techniques for delivering drugs to the tissues of 0003. There are a number of vision-threatening disorders the eye and the shortcomings thereof is Summarized. or diseases of the eye of a mammal including, but not limited 0008 Oral ingestion of a drug or injection of a drug at a to diseases of the retina, retinal pigment epithelium (RPE) site other than the eye can provide a drug systemically, and choroid. Such vision threatening diseases include ocular however Such a systemic administration does not provide neovascularization, ocular inflammation and retinal degen effective levels of the drug specifically to the eye. In many erations. Examples of these disease states include diabetic ophthalmic disorders involving the retina, posterior tract, retinopathy, chronic glaucoma, retinal detachment, sickle and optic nerve, adequate levels of the drug cannot be cell retinopathy, age-related macular degeneration, retinal achieved or maintained by oral or parenteral routes of neovascularization, Subretinal neovascularization; rubeosis administration. Thus, further and repeated administration of iritis inflammatory diseases, chronic posterior and pan uvei the drug would be necessary to achieve the desired or tis, neoplasms, retinoblastoma, pseudoglioma, neovascular adequate levels of concentration of the drug. Such further glaucoma; neovascularization resulting following a com and repeated administrations of Such drugs may produce bined vitrectomy-2 and lensectomy, vascular diseases, reti undesired systemic toxicity. nal ischemia, choroidal vascular insufficiency, choroidal thrombosis, neovascularization of the optic nerve, diabetic 0009 Ophthalmic conditions have also been treated macular edema, cystoid macular edema, macular edema, using drugs applied directly to the eye in either liquid or retinitis pigmentosa, retinal vein occlusion, proliferative ointment form. This route of administration (i.e., topical vitreoretinopathy, angioid streak, and retinal artery occlu administration) is only effective in treating problems involv Sion, and neovascularization due to penetration of the eye or ing the Superficial Surface of the eye and diseases that ocular injury. involve the cornea and anterior segment of the eye. Such as conjunctivitis. Topical administration of drugs is not effec 0004 Age-related macular degeneration (AMD) is the tive in achieving adequate concentrations of a drug(s) in the leading cause of irreversible severe central vision loss in Sclera, vitreous, or posterior segment of the eye. In addition, Caucasians fifty years old and older in the United States. topical eye drops may drain from the eye through the According to the 1990 U.S. census, approximately 750,000 nasolacrimal duct and into the systemic circulation, further people over 65 years of age were estimated as severe visual diluting the medication and risking unwanted Systemic side impairment in one or both eyes from AMD.
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