New treatment options for noninfectious uveitis

Developments in Ophthalmology

Volumn 51, Issue , 2012, Pages 134-161

  Gomes Bittencourt, Millena ^a   Sepah, Yasir Jamal ^a   Do, Diana V ^a   Agbedia, Owhofasa ^a   Akhtar, Abeer ^a   Liu, Hongting ^a   Akhlaq, Anam ^a   Annam, Rachel ^a   Ibrahim, Mohamed ^a   Nguyen, Quan Dong ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; IMMUNOLOGIC FACTOR; IMMUNOSUPPRESSIVE AGENT;

ANIMAL; ARTICLE; DRUG ADMINISTRATION ROUTE; DRUG IMPLANT; HUMAN; IONTOPHORESIS; METHODOLOGY; PRACTICE GUIDELINE; STANDARD; UVEITIS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; DRUG ADMINISTRATION ROUTES; DRUG IMPLANTS; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSIVE AGENTS; IONTOPHORESIS; PRACTICE GUIDELINES AS TOPIC; UVEITIS;

EID: 84860847076     PISSN: 02503751     EISSN: 16622790     Source Type: Book Series    
DOI: 10.1159/000336338     Document Type: Article

References (116)

1. Jabs DA, Nussenblatt RB, Rosenbaum JT: Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509-516.
2. Whitcup S: Uveitis 2003: Diagnosis and Management of Ocular Inflammation in the 21st Century: The uveitic syndromes -autoimmune and posterior uveitis: sarcoidosis. Uveitis Subspecialty Day Program and abstracts of the American Academy of Ophthalmology 2 Annual Meeting, Anaheim, November 2003.
3. Loh AR, Acharya NR: Incidence rates and risk factors for ocular complications and vision loss in HLA-B27-associated uveitis. Am J Ophthalmol 2010; 150:534e2-542e2.
4. Gritz DC, Wong IG: Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;17:491-500. (Pubitemid 38293104)
5. Nussenblatt RB: The natural history of uveitis. Int Ophthalmol 1990;14:303-308. (Pubitemid 20350862)
6. Darrell RW, Wagener HP, Kurland LT: Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol 1962;68:502-514.
7. Suttorp-Schulten MS, Rothova A: The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol 1996;80:844-848. (Pubitemid 26345317)
8. Suhler EB, Lloyd MJ, Choi D, Rosenbaum JT, Austin DF: Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest. Am J Ophthalmol 2008;146:890e8-896e8.
9. Durrani OM, Tehrani NN, Marr JE, Moradi P, Stavrou P, Murray PI: Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol 2004;88: 1159-1162. (Pubitemid 39141376)
10. Beraud E, Kotake S, Caspi RR, et al.: Control of experimental autoimmune uveoretinitis by low dose T cell vaccination. Cell Immunol 1992;140:112-122.
11. Pennesi G, Caspi RR: Genetic control of susceptibility in clinical and experimental uveitis. Int Rev Immunol 2002;21:67-88. (Pubitemid 34791934)
12. Heiligenhaus A, Thurau S, Hennig M, Grajewski RS, Wildner G: Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease. Graefes Arch Clin Exp Ophthalmol 2010;248:1531-1551.
13. Hoekzema R, Murray PI, van Haren MA, Helle M, Kijlstra A: Analysis of interleukin-in endotoxininduced uveitis. Invest Ophthalmol Vis Sci 1991; 32:88-95.
14. Ohta K, Yamagami S, Taylor AW, Streilein JW: IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2000;41:2591-2599. (Pubitemid 30624387)
15. Caspi R: Autoimmunity in the immune privileged eye: pathogenic and regulatory T cells. Immunol Res 2008;42:41-50.
16. von Toerne C, Sieg C, Kaufmann U, Diedrichs-Mohring M, Nelson PJ, Wildner G: Effector T cells driving monophasic vs. relapsing/remitting experimental autoimmune uveitis show unique pathway signatures. Mol Immunol 2010;48:272-280.
17. Horai R, Caspi RR: Cytokines in autoimmune uveitis. J Interferon Cytokine Res 2011;31:733-744.
18. Barton K, McLauchlan MT, Calder VL, Lightman S: The kinetics of cytokine mRNA expression in the retina during experimental autoimmune uveoretinitis. Cell Immunol 1995;164:133-140.
19. Haruta H, Ohguro N, Fujimoto M, et al.: Blockade of interleukin-signaling suppresses not only th but also interphotoreceptor retinoid binding proteinspecific Th by promoting regulatory T cells in experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2011;52:3264-3271.
20. Ishida W, Fukuda K, Higuchi T, Kajisako M, Sakamoto S, Fukushima A: Dynamic changes of microRNAs in the eye during the development of experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2011;52:611-617.
21. Jha P, Sohn JH, Xu Q, et al.: The complement system plays a critical role in the development of experimental autoimmune anterior uveitis. Invest Ophthalmol Vis Sci 2006;47:1030-1038. (Pubitemid 46768336)
22. Charteris DG, Barton K, McCartney AC, Lightman SL: CD4+ lymphocyte involvement in ocular Behcet's disease. Autoimmunity 1992;12:201-206.
23. George RK, Chan CC, Whitcup SM, Nussenblatt RB: Ocular immunopathology of Behcet's disease. Surv Ophthalmol 1997;42:157-162. (Pubitemid 27441291)
24. Whitcup SM, Chan CC, Li Q, Nussenblatt RB: Expression of cell adhesion molecules in posterior uveitis. Arch Ophthalmol 1992;110:662-666.
25. Durrani OM, Meads CA, Murray PI: Uveitis: a potentially blinding disease. Ophthalmologica 2004; 218:223-236. (Pubitemid 38969828)
26. Pato E, Munoz-Fernandez S, Francisco F, et al.: Systematic review on the effectiveness of immunosuppressants and biological therapies in the treatment of autoimmune posterior uveitis. Semin Arthritis Rheum 2011;40:314-323.
27. Jabs DA, Rosenbaum JT, Foster CS, et al.: Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2000; 130:492-513.
28. Larson T, Nussenblatt RB, Sen HN: Emerging drugs for uveitis. Expert Opin Emerg Drugs 2011;16:309-322.
29. Jaffe GJ, Martin D, Callanan D, Pearson PA, Levy B, Comstock T: Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirtyfour-week results of a multicenter randomized clinical study. Ophthalmology 2006;113:1020-1027. (Pubitemid 43795240)
30. Callanan DG, Jaffe GJ, Martin DF, Pearson PA, Comstock TL: Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results. Arch Ophthalmol 2008;126:1191-1201.
31. Anglade E, Yatscoff R, Foster R, Grau U: Nextgeneration calcineurin inhibitors for ophthalmic indications. Expert Opin Investig Drugs 2007;16: 1525-1540.
32. Lee RW, Schewitz LP, Nicholson LB, Dayan CM, Dick AD: Steroid refractory CD4+ T cells in patients with sight-threatening uveitis. Invest Ophthalmol Vis Sci 2009;50:4273-4278.
33. Pujari SS, Kempen JH, Newcomb CW, et al.: Cyclophosphamide for ocular inflammatory diseases. Ophthalmology 2010;117:356-365.
34. Nguyen QD, Hatef E, Kayen B, et al.: A cross-sectional study of the current treatment patterns in noninfectious uveitis among specialists in the United States. Ophthalmology 2011;118:184-190.
35. Ikeda E, Hikita N, Eto K, Mochizuki M: Tacrolimusrapamycin combination therapy for experimental autoimmune uveoretinitis. Jpn J Ophthalmol 1997; 41:396-402. (Pubitemid 28097390)
36. Kilmartin DJ, Forrester JV, Dick AD: Tacrolimus (FK506) in failed cyclosporin A therapy in endogenous posterior uveitis. Ocul Immunol Inflamm 1998;6:101-109. (Pubitemid 28380074)
37. Sloper CM, Powell RJ, Dua HS: Tacrolimus (FK506) in the treatment of posterior uveitis refractory to cyclosporine. Ophthalmology 1999;106:723-728. (Pubitemid 30194312)
38. Kempen JH, Daniel E, Gangaputra S, et al.: Methods for identifying long-term adverse effects of treatment in patients with eye diseases: the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Ophthalmic Epidemiol 2008; 15:47-55. (Pubitemid 351311499)
39. Okada AA: The dream of biologics in uveitis. Arch Ophthalmol 2010;128:632-635.
40. Okada AA: Immunomodulatory therapy for ocular inflammatory disease: a basic manual and review of the literature. Ocul Immunol Inflamm 2005;13: 335-351. (Pubitemid 41702757)
41. Dumont F: Cyclosporine A and tacrolimus (FK-506) immunosuppression through immunophilindependent inhibition of calcineurin function. In: Lieberman RMA, ed. Principles of Drug Development in Transplantation and Autoimmunity. New York: Chapman and Hall 1996;175-205.
42. Ho S, Clipstone N, Timmermann L, et al.: The mechanism of action of cyclosporin A and FK506. Clin Immunol Immunopathol 1996;80:S40-S45.
43. Cho ML, Cho CS, Min SY, et al.: Cyclosporine inhibition of vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Arthritis Rheum 2002;46:1202-1209.
44. Schreiber SL, Crabtree GR: The mechanism of action of cyclosporin A and FK506. Immunol Today 1992;13:136-142.
45. Stalder M, Birsan T, Hubble RW, Paniagua RT, Morris RE: In vivo evaluation of the novel calcineurin inhibitor ISATX in non-human primates. J Heart Lung Transplant 2003;22:1343-1352. (Pubitemid 37522038)
46. Kuglstatter A, Mueller F, Kusznir E, et al.: Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA (voclosporin). Acta Crystallogr D Biol Crystallogr 2011; 67:119-123.
47. Sepah YJ ME, Metcalf B, Khwaja A, Channa R, Ibrahim M, Hatef E, Heo J, Hee JL, Rentiya ZS DD, Nguyen QD: Voclosporin: a potentially promising therapeutic agent for noninfectious uveitis. Expert Rev Ophthalmol 2011;6:281-286.
48. Anglade E, Aspeslet LJ, Weiss SL: A new agent for the treatment of noninfectious uveitis: rationale and design of three LUMINATE (Lux Uveitis Multicenter Investigation of a New Approach to Treatment) trials of steroid-sparing voclosporin. Clin Ophthalmol 2008;2:693-702.
49. Kahan BD, Podbielski J, Napoli KL, Katz SM, Meier-Kriesche HU, Van Buren CT: Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation. Transplantation 1998;66:1040-1046. (Pubitemid 28513384)
50. Longoria J, Roberts RF, Marboe CC, Stouch BC, Starnes VA, Barr ML: Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection. J Thorac Cardiovasc Surg 1999;117:714-718. (Pubitemid 29163075)
51. Sehgal SN: Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc 2003;35:7S-14S. (Pubitemid 36547910)
52. Kim DH, Sarbassov DD, Ali SM, et al.: mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002;110:163-175. (Pubitemid 34876545)
53. Kim DH, Sarbassov DD, Ali SM, et al.: GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 2003;11:895-904. (Pubitemid 36566312)
54. Sehgal SN: Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998;31:335-340. (Pubitemid 28385231)
55. Shoshani T, Faerman A, Mett I, et al.: Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol Cell Biol 2002;22:2283-2293. (Pubitemid 34224633)
56. Attur MG, Patel R, Thakker G, Vyas P, et al.: Differential anti-inflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-and PGE production. Inflamm Res 2000;49:20-26. (Pubitemid 30073182)
57. Kwon YS, Hong HS, Kim JC, Shin JS, Son Y: Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo. Invest Ophthalmol Vis Sci 2005;46:454-460. (Pubitemid 40270322)
58. Gregory CR, Huie P, Billingham ME, Morris RE: Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels. Transplantation 1993;55: 1409-1418. (Pubitemid 23183261)
59. Guba M, von Breitenbuch P, Steinbauer M, et al.: Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8:128-135. (Pubitemid 34155123)
60. Shuchman M: Trading restenosis for thrombosis? New questions about drug-eluting stents. N Engl J Med 2006;355:1949-1952. (Pubitemid 44708012)
61. Rapamune (package insert). Philadelphia, Wyeth Pharmaceuticals, 2008.
62. Shanmuganathan VA, Casely EM, Raj D, et al.: The efficacy of sirolimus in the treatment of patients with refractory uveitis. Br J Ophthalmol 2005;89: 666-669. (Pubitemid 40780569)
63. Nida H, Sen TAL, Meleth AD, Smith WM, Nussenblatt RB: Subconjunctival sirolimus for the treatment of active anterior uveitis: results of a pilot trial, in press.
64. NCT00908466. Cgi. http://clinicaltrialsgov/ct2/show/NCT00908466.
65. Mohamed A, Ibrahim AW, Rentiya Z, Sepah YJ, Leder HA, Hatef E, Naor J, Shams NK, Dunn JP, Nguyen QD: Sirolimus as Therapeutic Approach to Uveitis: A Randomized Study to Assess the Safety and Bioactivity of Intravitreal and Subconjunctival Injections of Sirolimus in Patients with Non-Infectious Uveitis (The Save Study). ARVO, Fort Lauderdale, April 2011, abstract 4295.
66. Lee FF, Foster CS: Pharmacotherapy of uveitis. Expert Opin Pharmacother 2010;11:1135-1146.
67. Rodriguez-Martinez S, Cancino-Diaz ME, Jimenez-Zamudio L, Garcia-Latorre E, Cancino-Diaz JC: TLRs and NODs mRNA expression pattern in healthy mouse eye. Br J Ophthalmol 2005;89:904-910. (Pubitemid 40904819)
68. Gupta D, Agarwal R, Aggarwal AN, Jindal SK: Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. Eur Res J 2007;30:508-516. (Pubitemid 351182075)
69. Yanagihori H, Oyama N, Nakamura K, Mizuki N, Oguma K, Kaneko F: Role of IL-12B promoter polymorphism in Adamantiades-Behcet's disease susceptibility: an involvement of Th immunoreactivity against Streptococcus sanguinis antigen. J Invest Dermatol 2006;126:1534-1540.
70. Saari KM, Vilppula A, Lassus A, Leirisalo M, Saari R: Ocular inflammation in Reiter's disease after Salmonella enteritis. Am J Ophthalmol 1980;90:63-68. (Pubitemid 10033932)
71. Taurog JD, Richardson JA, Croft JT, et al.: The germfree state prevents development of gut and joint inflammatory disease in HLA-B transgenic rats. J Exp Med 1994;180:2359-2364. (Pubitemid 24351619)
72. Chang JH, McCluskey PJ, Wakefield D: Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease. Br J Ophthalmol 2006;90:103-108. (Pubitemid 43029907)
73. Rosenbaum JT, Rosenzweig HL, Smith JR, Martin TM, Planck SR: Uveitis secondary to bacterial products. Ophthalmic Res 2008;40:165-168. (Pubitemid 351562897)
74. McGonagle D, Savic S, McDermott MF: The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. Semin Immunopathol 2007;29: 303-313. (Pubitemid 47416222)
75. Stojanov S, Kastner DL: Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 2005;17:586-599. (Pubitemid 41527820)
76. Rosenzweig HL, Galster KT, Planck SR, Rosenbaum JT: NOD expression in the eye and functional contribution to IL-1beta-dependent ocular inflammation in mice. Invest Ophthalmol Vis Sci 2009;50: 1746-1753.
77. Rosenzweig HL, Planck SR, Rosenbaum JT: NLRs in immune privileged sites. Curr Opin Pharmacol 2011;11:423-428.
78. Zhang H: Anti-IL-1beta therapies. Recent Pat DNA Gene Seq 2011;5:126-135.
79. Hoffman HM, Amar NJ, Cartwright RC, et al.: Durability of response to rilonacept (IL-Trap) in a phase study of patients with cryopyrin-associated periodic syndromes: Familial cold auto-inflammatory syndrome and Muckle-Wells syndrome; in Am Acad Allergy Asthma Immunol Meet, Philadelphia, March 2008.
80. Arcalyst Resource Center Patient Information Brochure. Tarrytown, Regeneron Pharmaceuticals, 2008.
81. Ilaris (canakinumab) package insert. East Hanover, Novartis Pharmaceutical Corp.
82. Kineret (anakinra) package insert. Thousand Oaks, Amgen.
83. Geiler J, McDermott MF: Gevokizumab, an anti-IL-1beta mAb for the potential treatment of type and diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther 2010;12:755-769.
84. Gül A, Artim Esen B, Solinger A, Giustino L, Tugal Tutkun I: Safe, rapid-onset, and sustained biological activity of il-beta regulating antibody XOMA 052 in resistant uveitis of Behçet's disease: preliminary results of a pilot trial. Ann Rheum Dis 2010; 69(Suppl 3):178.
85. Yoshimura T, Sonoda KH, Ohguro N, et al.: Involvement of Th cells and the effect of anti-IL-6 therapy in autoimmune uveitis. Rheumatology (Oxford) 2009;48:347-354.
86. Haruta H, Ohguro N, Fujimoto M, et al.: Blockade of interleukin-signaling suppresses not only th but also interphotoreceptor retinoid binding proteinspecific Th by promoting regulatory T cells in experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2011;52:3264-3271.
87. Hohki S, Ohguro N, Haruta H, et al.: Blockade of interleukin-signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th responses. Exp Eye Res 2010;91: 162-170.
88. RoACTEMRA® (tocilizumab) summary of product characteristics. Roche, 2011.
89. Jones G, Sebba A, Gu J, et al.: Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010;69:88-96.
90. Smolen JS, Beaulieu A, Rubbert-Roth A, et al.: Effect of interleukin-receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987-997. (Pubitemid 351392039)
91. Nishimoto N, Yoshizaki K, Maeda K, et al.: Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 2003;30:1426-1435. (Pubitemid 36835435)
92. Nishimoto N, Yoshizaki K, Miyasaka N, et al.: Treatment of rheumatoid arthritis with humanized anti-interleukin-receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50:1761-1769. (Pubitemid 38725087)
93. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J: Long-term safety and efficacy of tocilizumab, an anti-IL-receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 2009;68:1580-1584.
94. Genovese MC, McKay JD, Nasonov EL, et al.: Interleukin-receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008;58:2968-2980.
95. Choy E: RADIATE: more treatment options for patients with an inadequate response to tumor necrosis factor antagonists. Nat Clin Pract Rheumatol 2009;5:66-67.
96. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R: Ophthalmic drug delivery systems -recent advances. Prog Retin Eye Res 1998;17:33-58. (Pubitemid 28040752)
97. Gurny R, Kaltsatos V, Deshpande AA, Zignani M, Percicot C, Baeyens V: Ocular drug delivery in veterinary medicine. Adv Drug Deliv Rev 1997;28: 335-361. (Pubitemid 28033907)
98. Diepold RW KJ, Himber J, Gurny R, Lee VHL, Robinson JR, et al.: Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops as a novel depot formulation (nanoparticles). Graefes Arch Clin Exp Ophthalmol 1989;227:188-193. (Pubitemid 19066688)
99. Zimmer AK CP, Saettone MF, Zerbe H, Kreuter J: Evaluation of pilocarpine-loaded albumin particles as controlled drug delivery systems for the eye. 2. Coadministration with Bioadhesive and Viscous Polymer. J Control Release 1995;33:31-46.
100. Vandervoort J, Ludwig A: Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use. Eur J Pharm Biopharm 2004;57: 251-261. (Pubitemid 38283701)
101. Marchal-Heussler L FH, Devissaguet JP, Hoffman M, Maincent P: Colloidal drug delivery systems for the eye. A comparison of the efficacy of three different polymers: poly-isobutylcyanoacrylate, polylactic-coglycolic acid, poly-epsilon-caprolactone. Pharm Sci 1992;2:98-104.
102. Bourges J-L, Gautier SE, Delie F, et al.: Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci 2003;44:3562-3569. (Pubitemid 36909796)
103. Eljarrat-Binstock E, Pe'er J, Domb AJ: New techniques for drug delivery to the posterior eye segment. Pharm Res 2010;27:530-543.
104. Moritera T, Ogura Y, Yoshimura N, et al.: Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 1992;33:3125-130.
105. Guidetti B, Azema J, Malet-Martino M, Martino R: Delivery systems for the treatment of proliferative vitreoretinopathy: materials, devices and colloidal carriers. Curr Drug Deliv 2008;5:7-19. (Pubitemid 351225629)
106. Saishin Y, Silva RL, Saishin Y, et al.: Periocular injection of microspheres containing PKC inhibits choroidal neovascularization in a porcine model. Invest Ophthalmol Vis Sci 2003;44:4989-4993. (Pubitemid 37315317)
107. Carrasquillo KG, Ricker JA, Rigas IK, Miller JW, Gragoudas ES, Adamis AP: Controlled delivery of the anti-VEGF aptamer EYE with poly(lacticco-glycolic) acid microspheres. Invest Ophthalmol Vis Sci 2003;44:290-299. (Pubitemid 36134287)
108. Eljarrat-Binstock E, Domb AJ: A non-invasive ocular drug delivery. J Control Release 2006;110:479-489.
109. Kasting GB: Theoretical models for iontophoretic delivery. Adv Drug Deliv Rev 1992;9:177-199.
110. Pikal MJ: The role of electroosmotic flow in transdermal iontophoresis. Adv Drug Deliv Rev 2001;46: 281-305.
111. Molokhia SA, Jeong EK, Higuchi WI, Li SK: Examination of barriers and barrier alteration in transscleral iontophoresis. J Pharm Sci 2008;97: 831-844. (Pubitemid 351293884)
112. Behar-Cohen FF, Aouni A EI, Gautier S, et al.: Transscleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels. Exp Eye Res 2002;74:51-59. (Pubitemid 34948265)
113. Sarraf D, Equi RA, Holland GN, Yoshizumi MO, Lee DA: Transscleral iontophoresis of foscarnet. Am J Ophthalmol 1993;115:748-754. (Pubitemid 23171601)
114. Chauvaud D, Behar-Cohen FF, Parel JM, Renard G: Transscleral Iontophoresis of cortcicosteoids: phase II clinical trial. Invest Ophthalmol Vis Sci 2000; 41:S79-S80.
115. Behar-Cohen F, Halhal M, Renard G, Bejjani RA: Corneal graft rejection and corticoid iontophoresis: case reports. J Fr Ophtalmol 2003;26:391-395. (Pubitemid 36576029)
116. Behar-Cohen FF, Halhal M, BenEzra D, Chauvaud D, Renard G: Reversal of corneal graft rejection by iontophoresis of methylprednisolone. Invest Ophthalmol Vis Sci 2002;43:U504-U504.