The eye is probably the most attractive site of the body for treatment using locally delivered therapeutic agents. An ideal indication for such an approach is noninfectious posterior uveitis. Since intraocular structures of the posterior segment are difficult to reach and are otherwise accessible only by systemic treatment, current interest is focused on the pros and cons of intravitreal drug delivery. Because of its chronic and recurrent nature, the long-term release of anti-inflammatory agents is a major treatment goal. Intravitreal injections, intravitreal implants and biodegradable devices are the most commonly used and approved approaches to deliver various agents to the vitreous. Because of their broad and potent effects, corticosteroids (CS) have been the first-line candidates for intraocular delivery. An increasing spectrum of CS preparations including nondegradable and biodegradable devices is currently available. Since repeated and long-term applications bear the risk of steroid-related complications such as increased intraocular pressure and cataract, alternative agents are currently being tested. Intravitreal injection of methotrexate, anti-VEGF (vascular endothelial growth factor), anti-TNFα (tumor necrosis factor α) and sirolimus have also been applied in patients with conflicting results. Intravitreal treatment has significantly reduced the incidence of adverse effects compared to systemic application, but due to greater ocular side effects there are still some limitations.

1.
Gregerson DS, Heuss ND, Lehmann U, McPherson SW: Evidence for extrathymic generation of regulatory T cells specific for a retinal antigen. Ophthalmic Res 2008;40:154–159.
2.
Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA, Thorne JE: Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the Multicenter Uveitis Steroid Treatment trial. Ophthalmology 2011;118:1916–1926.
3.
Pavesio C, Zierhut M, Bairi K, Comstock TL, Usner DW: Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis. Ophthalmology 2010;117:567–575.
4.
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.
5.
Razeghinejad MR, Katz LJ: Steroid-induced iatrogenic glaucoma. Ophthalmic Res 2012;47:66–80.
6.
Menezo V, Lau C, Comer M, Lightman S: Clinical outcome of chronic immunosuppression in patients with non-infectious uveitis. Clin Exp Ophthalmol 2005;33:16–21.
7.
Sallam A, Taylor SRJ, Lightman S: Review and update of intraocular therapy in noninfectious uveitis. Curr Opin Ophthalmol 2011;22:517–522.
8.
Roesel M, Gutfleisch M, Heinz C, Heimes B, Zurek-Imhoff B, Heiligenhaus A: Intravitreal and orbital floor triamcinolone acetonide injections in noninfectious uveitis: a comparative study. Ophthalmic Res 2009;42:81–86.
9.
Maca SM, Abela-Formanek C, Kiss CG, Sacu SG, Benesch T, Barisani-Asenbauer T: Intravitreal triamcinolone for persistent cystoid macular oedema in eyes with quiescent uveitis. Clin Exp Ophthalmol 2009;37:389–396.
10.
Sallam A, Taylor SR, Habot-Wilner Z, Elgohary M, Do HH, McCluskey P, Lightman S: Repeat intravitreal triamcinolone acetonide injections in uveitic macular oedema. Acta Ophthalmol 2012;90:e323–e325.
11.
Tuncer S, Yilmaz S, Urgancioglu M, Tugal-Tutkun I: Results of intravitreal triamcinolone acetonide (IVTA) injection for the treatment of panuveitis attacks in patients with Behçet disease. J Ocul Pharmacol Ther 2007;23:395–401.
12.
Chan WM, Lim E, Liu DT, Law RW, Lam DS: Intravitreal triamcinolone acetonide for choroidal granuloma in sarcoidosis. Am J Ophthalmol 2005;139:1116–1118.
13.
Moreker MR, Lodhi SA, Pathengay A: Role of intravitreal triamcinolone as an adjuvant in the management of Vogt-Koyanagi-Harada disease. Indian J Ophthalmol 2007;55:479–80.
14.
Ozdemir H, Karacorlu M, Karacorlu S: Intravitreal triamcinolone acetonide in sympathetic ophthalmia. Graefes Arch Clin Exp Ophthalmol 2005;243:734–736.
15.
Jonas JB: Intravitreal triamcinolone acetonide: a change in a paradigm. Ophthalmic Res 2006;38:218–245.
16.
Rush R, Sheth S: Fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone administration. Indian J Ophthalmol 2012;60:141–143.
17.
Vertes D, Snyers B, De Potter P: Cytomegalovirus retinitis after low-dose intravitreous triamcinolone acetonide in an immunocompetent patient: a warning for the widespread use of intravitreous corticosteroids. Int Ophthalmol 2010;30:595–597.
18.
Nguyen QD, Callanan D, Dugel P, Godfrey DG, Goldstein DA,Wilensky JT: Treating chronic noninfectious posterior segment uveitis: the impact of cumulative damage. Proceedings of an expert panel roundtable discussion. Retina 2006;(suppl):1–16.
19.
Arndt C, Meunier I, Rebollo O, Martinenq C, Hamel C, Hattenbach LO: Electrophysiological retinal pigment epithelium changes observed with indocyanine green, trypan blue and triamcinolone. Ophthalmic Res 2010;44:17–23.
20.
Morse LS, Ashton P, Levy B, Mann ES, Eliott D: Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3- year multicenter, randomized, controlled clinical trial. Ophthalmology 2011;118:1580–1586.
21.
Jain N, Stinnett SS, Jaffe GJ: Prospective study of a fluocinolone acetonide implant for chronic macular edema from central retinal vein occlusion thirty-six-month results. Ophthalmology 2012;119:132–137.
22.
Williams GA, Haller JA, Kuppermann BD, Blumenkranz MS, Weinberg DV, Chou C, Whitcup SM, Dexamethasone DDS Phase II Study Group: Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol 2009;147:1048–1054, 1054.e1–e2.
23.
Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, Li XY, Cui H, Whitcup SM, Ozurdex HURON Study Group: Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545–553.
24.
Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL: Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology 2009;116:797–801.
25.
Bae JH, Lee SC: Effect of intravitreal methotrexate and aqueous humor cytokine levels in refractory retinal vasculitis in Behcet disease. Retina 2012;32:1395–402.
26.
Campochiaro PA, Hafiz G, Shah SM, Bloom S, Brown DM, Busquets M, Ciulla T, Feiner L, Sabates N, Billman K, Kapik B, Green K, Kane F, Famous Study Group: Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert. Ophthalmology 2010;117:1393–1399.e3.
27.
Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon Y- H, Jacques M- L, Jiao J, Li X- Y, Whitcup SM: Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–1146, e1133.
28.
Boyer DS, Faber DJ, Gupta SK, Patel SS, Tabandeh H, Li XY, Liu CC, Lou J, Whitcup SM, the Ozurdex Champlain Study Group: Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 2011;31:915–923.
29.
Pleyer U, Klamann M, Winterhalter S, Thurau S: Ozurdex: a new therapeutic option in uveitis – clinical outcome from two German uveitis centers. Abstract ARVO Annual Meeting, Fort Lauderdale, May 2012.
30.
Dueckers G, Guellac N, Arbogast M, Dannecker G, Foeldvari I, Frosch M, Ganser G, Heiligenhaus A, Horneff G, Illhardt A, Kopp I, Krauspe R, Markus B, Michels H, Schneider M, Singendonk W, Sitter H, Spamer M, Wagner N, Niehues T: Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis. Clin Immunol 2012;142:176–193.
31.
Wickremasinghe SS, Ojaimi E, Lim L, Stawell R, McKelvie P, Zamir E: Intravitreal methotrexate as adjunctive, palliative therapy in intraocular T-cell lymphoma. Ocul Immunol Inflamm 2010;18:184–186.
32.
Hardwig PW, Pulido JS, Erie JC, Baratz KH, Buettner H: Intraocular methotrexate in ocular diseases other than primary central nervous system lymphoma. Am J Ophthalmol 2006;142:883–885.
33.
Palakurthi NK, Correa ZM, Augsburger JJ, Banerjee RK:Toxicity of a biodegradable microneedle implant loaded with methotrexate as a sustained release device in normal rabbit eye: a pilot study. J Ocul Pharmacol Th 2011;27:151–156.
34.
Patel RD, Momi RS, Hariprasad SM: Review of ranibizumab trials for neovascular age- related macular degeneration. Semin Ophthalmol 2011;26:372–379.
35.
El- Mollayess GM, Noureddine BN, Bashshur ZF: Bevacizumab and neovascular age related macular degeneration: pathogenesis and treatment. Semin Ophthalmol 2011;26:69– 76.
36.
Arevalo JF, Adan A, Berrocal MH, Espinoza JV, Maia M, Wu L, Roca JA, Quiroz- Mercado H, Ruiz-Moreno JM, Serrano MA: Intravitreal bevacizumab for inflammatory choroidal neovascularization: results from the Pan-American Collaborative Retina Study Group at 24 months. Retina 2011;31:353–363.
37.
Julián K, Terrada C, Fardeau C, Cassoux N, Français C, LeHoang P, Bodaghi B: Intravitreal bevacizumab as first local treatment for uveitis-related choroidal neovascularization: long-term results. Acta Ophthalmol 2011;89:179–184.
38.
Rouvas A, Petrou P, Douvali M, Ntouraki A, Vergados I, Georgalas I, Markomichelakis N: Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularization. Retina 2011;31:871–879.
39.
Acharya NR, Hong KC, Lee SM: Ranibizumab for refractory uveitis-related macular edema. Am J Ophthalmol 2009;148:303–309.
40.
Lasave AF, Zeballos DG, El- Haig WM, Díaz- Llopis M, Salom D, Arevalo JF: Short-term results of a single intravitreal bevacizumab (Avastin) injection versus a single intravitreal triamcinolone acetonide (Kenacort) injection for the management of refractory noninfectious uveitic cystoid macular edema. Ocul Immunol Inflamm 2009;17:423–430.
41.
Hazirolan D, Stübiger N, Pleyer U: Light on the Horizon: biologicals in Behçet uveitis. Acta Ophthalmol 2012, E-pub ahead of print.
42.
Melo GB, Moraes Filho MN, Rodrigues EB, Regatieri CV, Dreyfuss JL, Penha FM, Pinheiro MM, Coimbra RC, Haapalainen EF, Farah ME: Toxicity and retinal penetration of infliximab in primates. Retina 2012;32:606–612.
43.
Farvardin M, Afarid M, Mehryar M, Hosseini H: Intravitreal infliximab for the treatment of sight-threatening chronic noninfectious uveitis. Retina 2010;30:1530–1535.
44.
Giganti M, Beer PM, Lemanski N, Hartman C, Schartman J, Falk N: Adverse events after intravitreal infliximab (Remicade). Retina 2010;30:71–80.
45.
Shanmuganathan VA, Casely EM, Raj D, Powell RJ, Joseph A, Amoaku WM, Dua HS: The efficacy of sirolimus in the treatment of patients with refractory uveitis. Br J Ophthalmol 2005;89:666–669.
46.
Manzano RP, Peyman GA, Khan P, Kivilcim M, Chevez-Barrios P, Takahashi W: Testing intravitreal toxicity of rapamycin in rabbit eyes. Arq Bras Oftalmol 2009;72:18–22.
47.
Nguyen QD, Ibrahim M, Watters A: Primary endpoint results of the SAVE study – 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. Abstract ARVO Annual Meeting, Fort Lauderdale, May 2012.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.