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Noninfectious Uveitis: Emerging Therapies

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Posterior Uveitis

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Abstract

This chapter provides an overview of the up-and-coming therapies for the treatment of uveitis. The current era is by far the most exciting time to be a uveitis specialist in terms of our understanding of disease mechanisms as well as the expanding array of therapy options we have for our patients. There are multiple novel therapeutic agents, from small molecules to peptides to biologics that have shown promise in preclinical or early clinical studies. Additionally, there are biologic therapies that have been newly developed for systemic immune-mediated inflammatory diseases that have been unevaluated for uveitis. New methods of drug delivery are also reviewed, as targeted drug delivery to the eye promises to be one of the most effective methods of treating uveitis. This includes novel drug delivery devices as well as nanotechnology, dissolvable polymers, and liposomal drug delivery.

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References

  1. Tugal-Tutkun I, Pavesio C, De Cordoue A, Bernard-Poenaru O, Gul A. Use of Gevokizumab in patients with Behcet’s disease uveitis: an international, randomized, double-masked, placebo-controlled study and open-label extension study. Ocul Immunol Inflamm. 2018;26(7):1023–33.

    Google Scholar 

  2. Dick AD, Tugal-Tutkun I, Foster S, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013;120(4):777–87.

    PubMed  Google Scholar 

  3. Buggage RR, Levy-Clarke G, Sen HN, et al. A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behcet’s disease. Ocul Immunol Inflamm. 2007;15(2):63–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175–87.

    CAS  PubMed  Google Scholar 

  5. Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83(5):991–1001.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–51.

    CAS  PubMed  Google Scholar 

  7. Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61(12):1693–700.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Nirula A, Nilsen J, Klekotka P, et al. Effect of IL-17 receptor a blockade with brodalumab in inflammatory diseases. Rheumatology (Oxford). 2016;55(suppl 2):ii43–55.

    Google Scholar 

  9. Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol. 2015;42(6):912–9.

    CAS  PubMed  Google Scholar 

  10. Mugheddu C, Atzori L, Del Piano M, et al. Successful ustekinumab treatment of noninfectious uveitis and concomitant severe psoriatic arthritis and plaque psoriasis. Dermatol Ther. 2017;30(5):e12527.

    Google Scholar 

  11. Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol. 2017;76(1):60–9. e69

    CAS  PubMed  Google Scholar 

  12. Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol. 2014;32:513–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Khamashta M, Merrill JT, Werth VP, et al. Sifalimumab, an anti-interferon-alpha monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(11):1909–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Kalunian KC, Merrill JT, Maciuca R, et al. A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. 2016;75(1):196–202.

    PubMed  Google Scholar 

  15. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheum (Hoboken, NJ). 2017;69(2):376–86.

    CAS  Google Scholar 

  16. Bernard R. Lauwerys, Eric Hachulla, François Spertini, Estibaliz Lazaro, Christian Jorgensen, Xavier Mariette, Edwige Haelterman, Géraldine Grouard-Vogel, Bernard Fanget, Olivier Dhellin, Pierre Vandepapelière, Frédéric A. Houssiau, (2013) Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid. Arthritis & Rheumatism 65 (2):447–56

    Google Scholar 

  17. Guerreiro Castro S, Isenberg DA. Belimumab in systemic lupus erythematosus (SLE): evidence-to-date and clinical usefulness. Ther Adv Musculoskelet Dis. 2017;9(3):75–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Merrill JT, van Vollenhoven RF, Buyon JP, et al. Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(2):332–40.

    CAS  PubMed  Google Scholar 

  19. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon Beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34.

    CAS  PubMed  Google Scholar 

  20. Hartemann A, Bensimon G, Payan CA, et al. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013;1(4):295–305.

    CAS  PubMed  Google Scholar 

  21. Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365(22):2055–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407–15.

    Google Scholar 

  23. Goodyear M. Learning from the TGN1412 trial. BMJ (Clinical research ed). 2006;332(7543):677–8.

    Google Scholar 

  24. Tyrsin D, Chuvpilo S, Matskevich A, et al. From TGN1412 to TAB08: the return of CD28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(4 Suppl 98):45–8.

    PubMed  Google Scholar 

  25. Konig M, Rharbaoui F, Aigner S, Dalken B, Schuttrumpf J. Tregalizumab – a monoclonal antibody to target regulatory T cells. Front Immunol. 2016;7:11.

    PubMed  PubMed Central  Google Scholar 

  26. De Groot AS, Moise L, McMurry JA, et al. Activation of natural regulatory T cells by IgG fc-derived peptide “Tregitopes”. Blood. 2008;112(8):3303–11.

    PubMed  PubMed Central  Google Scholar 

  27. Dhillon S. Tofacitinib: a review in rheumatoid arthritis. Drugs. 2017;77(18):1987–2001.

    CAS  PubMed  Google Scholar 

  28. Healio. https://www.healio.com/ophthalmology/retina-vitreous/news/online/%7B7acf5955-5299-42c0-bcde-56687839e439%7D/santens-intravitreal-sirolimus-for-noninfectious-posterior-segment-uveitis-not-approved. Accessed 10 Jan 2018.

  29. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Ophthalmology. 2017;124(1):53–60.

    PubMed  Google Scholar 

  30. Sheppard JD, Torkildsen GL, Lonsdale JD, et al. Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. Ophthalmology. 2014;121(2):475–83.

    PubMed  Google Scholar 

  31. Tauber J, Karpecki P, Latkany R, et al. Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study. Ophthalmology. 2015;122(12):2423–31.

    PubMed  Google Scholar 

  32. Madri JA, Graesser D, Haas T. The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration. Biochem Cell Biol. 1996;74(6):749–57.

    CAS  PubMed  Google Scholar 

  33. Martin AP, de Moraes LV, Tadokoro CE, et al. Administration of a peptide inhibitor of alpha4-integrin inhibits the development of experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2005;46(6):2056–63.

    PubMed  Google Scholar 

  34. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.

    CAS  PubMed  Google Scholar 

  35. Kurose S, Ikeda E, Tokiwa M, Hikita N, Mochizuki M. Effects of FTY720, a novel immunosuppressant, on experimental autoimmune uveoretinitis in rats. Exp Eye Res. 2000;70(1):7–15.

    CAS  PubMed  Google Scholar 

  36. Commodaro AG, Peron JP, Lopes CT, et al. Evaluation of experimental autoimmune uveitis in mice treated with FTY720. Invest Ophthalmol Vis Sci. 2010;51(5):2568–74.

    PubMed  Google Scholar 

  37. Zarbin MA, Jampol LM, Jager RD, et al. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013;120(7):1432–9.

    PubMed  Google Scholar 

  38. Egwuagu CE, Larkin IJ. Therapeutic targeting of STAT pathways in CNS autoimmune diseases. JAK-STAT. 2013;2(1):e24134.

    PubMed  PubMed Central  Google Scholar 

  39. Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370(25):2377–86.

    PubMed  Google Scholar 

  40. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652–62.

    CAS  PubMed  Google Scholar 

  41. Huang J-F, Zhang Y, Hirakawa B. Evaluation of JAK inhibition with topical tofacitinib in an experimental autoimmune uveitis model (EAU). Association for Research in Vision and Ophthalmology Annual Meeting; 2013; Ft. Lauderdale.

    Google Scholar 

  42. Harris TJ, Grosso JF, Yen HR, et al. Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol. 2007;179(7):4313–7.

    CAS  PubMed  Google Scholar 

  43. Liu X, Lee YS, Yu CR, Egwuagu CE. Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J Immunol. 2008;180(9):6070–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Yu CR, Lee YS, Mahdi RM, Surendran N, Egwuagu CE. Therapeutic targeting of STAT3 (signal transducers and activators of transcription 3) pathway inhibits experimental autoimmune uveitis. PLoS One. 2012;7(1):e29742.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bae SC, Lee YH. Comparative efficacy and tolerability of monotherapy with leflunomide or tacrolimus for the treatment of rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials. Clin Rheumatol. 2018;37(2):323–30.

    PubMed  Google Scholar 

  46. Molina C, Modesto C, Martin-Begue N, Arnal C. Leflunomide, a valid and safe drug for the treatment of chronic anterior uveitis associated with juvenile idiopathic arthritis. Clin Rheumatol. 2013;32(11):1673–5.

    PubMed  Google Scholar 

  47. Bichler J, Benseler SM, Krumrey-Langkammerer M, Haas JP, Hugle B. Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis. Scand J Rheumatol. 2015;44(4):280–3.

    CAS  PubMed  Google Scholar 

  48. Fang CB, Zhou DX, Zhan SX, et al. Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats. PLoS One. 2013;8(4):e62071.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Diedrichs-Mohring M, Leban J, Strobl S, Obermayr F, Wildner G. A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2014;56(2):1147–57.

    PubMed  Google Scholar 

  50. Kumar N, Goldminz AM, Kim N, Gottlieb AB. Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med. 2013;11:96.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Xu H, Strassmann G, Chan CC, et al. Protective effect of the type IV phosphodiesterase inhibitor rolipram in EAU: protection is independent of IL-10-inducing activity. Invest Ophthalmol Vis Sci. 1999;40(5):942–50.

    CAS  PubMed  Google Scholar 

  52. Gooderham M, Papp K. Apremilast in the treatment of psoriasis and psoriatic arthritis. Skin Therapy Lett. 2015;20(5):1–6.

    CAS  PubMed  Google Scholar 

  53. Yadav UC, Kalariya NM, Ramana KV. Emerging role of antioxidants in the protection of uveitis complications. Curr Med Chem. 2011;18(6):931–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Nguyen AM, Rao NA. Oxidative photoreceptor cell damage in autoimmune uveitis. J Ophthalmic Inflamm Infect. 2010;1(1):7–13.

    PubMed  PubMed Central  Google Scholar 

  55. Saraswathy S, Rao NA. Photoreceptor mitochondrial oxidative stress in experimental autoimmune uveitis. Ophthalmic Res. 2008;40(3–4):160–4.

    CAS  PubMed  Google Scholar 

  56. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.

    PubMed  PubMed Central  Google Scholar 

  57. Wright JG, Christman JW. The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy. Am J Respir Med. 2003;2(3):211–9.

    CAS  PubMed  Google Scholar 

  58. Yadav UC, Shoeb M, Srivastava SK, Ramana KV. Amelioration of experimental autoimmune uveoretinitis by aldose reductase inhibition in Lewis rats. Invest Ophthalmol Vis Sci. 2011;52(11):8033–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Yadav UC, Srivastava SK, Ramana KV. Aldose reductase inhibition prevents endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2007;48(10):4634–42.

    PubMed  PubMed Central  Google Scholar 

  60. Di Filippo C, Zippo MV, Maisto R, et al. Inhibition of ocular aldose reductase by a new benzofuroxane derivative ameliorates rat endotoxic uveitis. Mediat Inflamm. 2014;2014:857958.

    Google Scholar 

  61. Suzuki J, Yoshimura T, Simeonova M, et al. Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2012;53(7):4158–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Nguyen QD, Merrill PT, Clark WL, et al. Intravitreal sirolimus for noninfectious uveitis: a phase III sirolimus study assessing double-masKed Uveitis TReAtment (SAKURA). Ophthalmology. 2016;123(11):2413–23.

    PubMed  Google Scholar 

  63. Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol. 2010;4:1201–6.

    PubMed  PubMed Central  Google Scholar 

  64. Shirinsky IV, Biryukova AA, Shirinsky VS. Simvastatin as an adjunct to conventional therapy of non-infectious uveitis: a randomized, open-label pilot study. Curr Eye Res. 2017;42(12):1713–8.

    CAS  PubMed  Google Scholar 

  65. Shalaby U. Diltiazem co treatment with cyclosporine for induction of disease remission in sight-threatening non-infectious intraocular inflammation. Jpn J Ophthalmol. 2017;61(2):169–78.

    CAS  PubMed  Google Scholar 

  66. Driot JY, Novack GD, Rittenhouse KD, Milazzo C, Pearson PA. Ocular pharmacokinetics of fluocinolone acetonide after Retisert intravitreal implantation in rabbits over a 1-year period. J Ocul Pharmacol Ther. 2004;20(3):269–75.

    CAS  PubMed  Google Scholar 

  67. Holbrook JT, Sugar EA, Burke AE, et al. Dissociations of the fluocinolone acetonide implant: the multicenter uveitis steroid treatment (MUST) trial and follow-up study. Am J Ophthalmol. 2016;164:29–36.

    CAS  PubMed  Google Scholar 

  68. Campochiaro PA, Hafiz G, Shah SM, et al. Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert. Ophthalmology. 2010;117(7):1393–9. e1393

    PubMed  Google Scholar 

  69. Reddy AK, Burkholder BM, Khan IR, Thorne JE. Iluvien implantation for uveitis and uveitic macular Edema. Ocul Immunol Inflamm. 2018;26(2):315–16.

    Google Scholar 

  70. Jaffe GJ, Lin P, Keenan RT, Ashton P, Skalak C, Stinnett SS. Injectable fluocinolone acetonide long-acting implant for noninfectious intermediate uveitis, posterior uveitis, and panuveitis: two-year results. Ophthalmology. 2016;123(9):1940–8.

    PubMed  Google Scholar 

  71. Humayun M, Santos A, Altamirano JC, et al. Implantable MicroPump for drug delivery in patients with diabetic macular Edema. Transl Vis Sci Technol. 2014;3(6):5.

    PubMed  PubMed Central  Google Scholar 

  72. clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02510794. Accessed 5 Nov 2017.

  73. Rawas-Qalaji M, Williams CA. Advances in ocular drug delivery. Curr Eye Res. 2012;37(5):345–56.

    CAS  PubMed  Google Scholar 

  74. Liu YC, Peng Y, Lwin NC, Wong TT, Venkatraman SS, Mehta JS. Optimization of subconjunctival biodegradable microfilms for sustained drug delivery to the anterior segment in a small animal model. Invest Ophthalmol Vis Sci. 2013;54(4):2607–15.

    CAS  PubMed  Google Scholar 

  75. Thackaberry EA, Farman C, Zhong F, et al. Evaluation of the toxicity of intravitreally injected PLGA microspheres and rods in monkeys and rabbits: effects of depot size on inflammatory response. Invest Ophthalmol Vis Sci. 2017;58(10):4274–85.

    CAS  PubMed  Google Scholar 

  76. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011;52(1):80–6.

    CAS  PubMed  Google Scholar 

  77. Whitcup SM, Robinson MR. Development of a dexamethasone intravitreal implant for the treatment of noninfectious posterior segment uveitis. Ann N Y Acad Sci. 2015;1358:1–12.

    CAS  PubMed  Google Scholar 

  78. Souza MC, Fialho SL, Souza PA, Fulgencio GO, Da Silva GR, Silva-Cunha A. Tacrolimus-loaded PLGA implants: in vivo release and ocular toxicity. Curr Eye Res. 2014;39(1):99–102.

    CAS  PubMed  Google Scholar 

  79. Sakurai E, Nozaki M, Okabe K, Kunou N, Kimura H, Ogura Y. Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis. Invest Ophthalmol Vis Sci. 2003;44(11):4845–52.

    PubMed  Google Scholar 

  80. Jaffe GJ, Yang CS, Wang XC, Cousins SW, Gallemore RP, Ashton P. Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis. Ophthalmology. 1998;105(1):46–56.

    CAS  PubMed  Google Scholar 

  81. Dong X, Shi W, Yuan G, Xie L, Wang S, Lin P. Intravitreal implantation of the biodegradable cyclosporin a drug delivery system for experimental chronic uveitis. Graefes Arch Clin Exp Ophthalmol. 2006;244(4):492–7.

    CAS  PubMed  Google Scholar 

  82. Shi W, Chen M, Xie L, et al. A novel cyclosporine a drug-delivery system for prevention of human corneal rejection after high-risk keratoplasty: a clinical study. Ophthalmology. 2013;120(4):695–702.

    PubMed  Google Scholar 

  83. Lee SS, Kim H, Wang NS, et al. A pharmacokinetic and safety evaluation of an episcleral cyclosporine implant for potential use in high-risk keratoplasty rejection. Invest Ophthalmol Vis Sci. 2007;48(5):2023–9.

    PubMed  Google Scholar 

  84. Bock F, Matthaei M, Reinhard T, et al. High-dose subconjunctival cyclosporine a implants do not affect corneal neovascularization after high-risk keratoplasty. Ophthalmology. 2014;121(9):1677–82.

    PubMed  Google Scholar 

  85. Liu YC, Peng Y, Lwin NC, Venkatraman SS, Wong TT, Mehta JS. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model. PLoS One. 2013;8(8):e70419.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Liu YC, Ng XW, Teo EPW, et al. A biodegradable, sustained-released, tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model. Invest Ophthalmol Vis Sci. 2018;59(2):675–84.

    CAS  PubMed  Google Scholar 

  87. Manna S, Augsburger JJ, Correa ZM, Landero JA, Banerjee RK. Development of chitosan and polylactic acid based methotrexate intravitreal micro-implants to treat primary intraocular lymphoma: an in vitro study. J Biomech Eng. 2014;136(2):021018.

    PubMed  Google Scholar 

  88. Manna S, Banerjee RK, Augsburger JJ, Al-Rjoub MF, Donnell A, Correa ZM. Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes. Graefes Arch Clin Exp Ophthalmol. 2015;253(8):1297–305.

    CAS  PubMed  Google Scholar 

  89. Bioscience I. http://iconbioscience.com/verisome-drug-delivery-technology/. Accessed 13 Nov 2017.

  90. Janagam DR, Wu L, Lowe TL. Nanoparticles for drug delivery to the anterior segment of the eye. Adv Drug Deliv Rev. 2017;122:31–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Gan L, Han S, Shen J, et al. Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: improving preocular retention and ocular bioavailability. Int J Pharm. 2010;396(1–2):179–87.

    CAS  PubMed  Google Scholar 

  92. Han S, Shen JQ, Gan Y, et al. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability. Acta Pharmacol Sin. 2010;31(8):990–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Adibkia K, Javadzadeh Y, Dastmalchi S, Mohammadi G, Niri FK, Alaei-Beirami M. Naproxen-eudragit RS100 nanoparticles: preparation and physicochemical characterization. Colloids Surf B Biointerfaces. 2011;83(1):155–9.

    CAS  PubMed  Google Scholar 

  94. Katara R, Majumdar DK. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf B Biointerfaces. 2013;103:455–62.

    CAS  PubMed  Google Scholar 

  95. Adibkia K, Siahi Shadbad MR, Nokhodchi A, et al. Piroxicam nanoparticles for ocular delivery: physicochemical characterization and implementation in endotoxin-induced uveitis. J Drug Target. 2007;15(6):407–16.

    CAS  PubMed  Google Scholar 

  96. Adibkia K, Omidi Y, Siahi MR, et al. Inhibition of endotoxin-induced uveitis by methylprednisolone acetate nanosuspension in rabbits. J Ocul Pharmacol Ther. 2007;23(5):421–32.

    CAS  PubMed  Google Scholar 

  97. De Campos AM, Sanchez A, Alonso MJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin a. Int J Pharm. 2001;224(1–2):159–68.

    PubMed  Google Scholar 

  98. Badawi AA, El-Laithy HM, El Qidra RK, El Mofty H, El dally M. Chitosan based nanocarriers for indomethacin ocular delivery. Arch Pharm Res. 2008;31(8):1040–9.

    CAS  PubMed  Google Scholar 

  99. Yamaguchi M, Ueda K, Isowaki A, et al. Mucoadhesive properties of chitosan-coated ophthalmic lipid emulsion containing indomethacin in tear fluid. Biol Pharm Bull. 2009;32(7):1266–71.

    CAS  PubMed  Google Scholar 

  100. Alonso MJ, Sanchez A. The potential of chitosan in ocular drug delivery. J Pharm Pharmacol. 2003;55(11):1451–63.

    CAS  PubMed  Google Scholar 

  101. Granata G, Paterniti I, Geraci C, et al. Potential eye drop based on a calix[4]arene nanoassembly for curcumin delivery: enhanced drug solubility, stability, and anti-inflammatory effect. Mol Pharm. 2017;14(5):1610–22.

    CAS  PubMed  Google Scholar 

  102. Bochot A, Fattal E. Liposomes for intravitreal drug delivery: a state of the art. J Control Release. 2012;161(2):628–34.

    CAS  PubMed  Google Scholar 

  103. Kuppermann BD, Assil KK, Vuong C, et al. Liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for long-acting therapy of viral retinitis. J Infect Dis. 1996;173(1):18–23.

    CAS  PubMed  Google Scholar 

  104. Diaz-Llopis M, Martos MJ, Espana E, et al. Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients. Experimental toxicity and pharmacokinetics, and clinical trial. Doc Ophthalmol. 1992;82(4):297–305.

    CAS  PubMed  Google Scholar 

  105. Akula SK, Ma PE, Peyman GA, et al. Treatment of cytomegalovirus retinitis with intravitreal injection of liposome encapsulated ganciclovir in a patient with AIDS. Br J Ophthalmol. 1994;78(9):677–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Bochot A, Couvreur P, Fattal E. Intravitreal administration of antisense oligonucleotides: potential of liposomal delivery. Prog Retin Eye Res. 2000;19(2):131–47.

    CAS  PubMed  Google Scholar 

  107. Zhang R, Qian J, Li X, Yuan Y. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes. Br J Ophthalmol. 2017;101(12):1731–8.

    PubMed  Google Scholar 

  108. Lajavardi L, Camelo S, Agnely F, et al. New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis. J Control Release. 2009;139(1):22–30.

    CAS  PubMed  Google Scholar 

  109. Lajavardi L, Bochot A, Camelo S, et al. Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal peptide encapsulated in liposomes. Invest Ophthalmol Vis Sci. 2007;48(7):3230–8.

    PubMed  Google Scholar 

  110. Masuda I, Matsuo T, Yasuda T, Matsuo N. Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci. 1996;37(9):1914–20.

    CAS  PubMed  Google Scholar 

  111. Patane MA, Schubert W, Sanford T, et al. Evaluation of ocular and general safety following repeated dosing of dexamethasone phosphate delivered by transscleral iontophoresis in rabbits. J Ocul Pharmacol Ther. 2013;29(8):760–9.

    CAS  PubMed  Google Scholar 

  112. Olsen TW, Feng X, Wabner K, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142(5):777–87.

    CAS  PubMed  Google Scholar 

  113. Goldstein DA, Do D, Noronha G, Kissner JM, Srivastava SK, Nguyen QD. Suprachoroidal corticosteroid administration: a novel route for local treatment of noninfectious uveitis. Transl Vis Sci Technol. 2016;5(6):14.

    PubMed  PubMed Central  Google Scholar 

  114. Chen M, Li X, Liu J, Han Y, Cheng L. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release. 2015;203:109–17.

    CAS  PubMed  Google Scholar 

  115. Yeh S. Suprachoroidally injected CLS-TA improves visual acuity and macular Edema in noninfectious uveitis: results of the phase 3 PEACHTREE study. Paper presented at American Society of Retina Specialists; 2018 July 25; Vancouver, B.C.

    Google Scholar 

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Julie Schallhorn declares she does not have any conflict of interest. No human studies were carried out by the authors of this book. No animal studies were carried out by the authors of this book.

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Schallhorn, J. (2019). Noninfectious Uveitis: Emerging Therapies. In: Rao, N., Schallhorn, J., Rodger, D. (eds) Posterior Uveitis. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-030-03140-4_12

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