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Corticosteroids and Anti-Complement Therapy in Retinal Diseases

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Pharmacologic Therapy of Ocular Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 242))

Abstract

Corticosteroids are unique in that they are the one class of agents that acts upon most of the multiple processes in the pathophysiology of macular edema. Corticosteroids are capable of inhibiting prostaglandin and leukotriene synthesis as well as interfering with intercellular adhesion molecule-1 (ICAM-1), interleukin-6, VEGF-A, and stromal cell derived factor-1 pathways. Triamcinolone, dexamethasone, and fluocinolone have been extensively used in the treatment of retinal and choroidal vascular diseases. Sustained release implants of steroids have reduced the burden of repeated intravitreal injections necessary in most of the retinal diseases. Complement factors play an important role in the pathogenesis of age-related macular degeneration (AMD). Inhibitors of complement could provide a breakthrough in the treatment of dry AMD. Complement factor inhibitors, such as POT-4, lampalizumab, and eculizumab, have been tested in clinical trials for dry AMD with promising results. However, results of phase 3 trials are awaited.

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References

  • Antonetti DA, Wolpert EB, DeMaio L, Harhaj NS, Scaduto RC Jr (2002) Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80(4):667–677

    Article  CAS  PubMed  Google Scholar 

  • Boyer DS, Faber D, Gupta S, Patel SS, Tabandeh H, Li XY et al (2011) Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 31(5):915–923

    Article  CAS  PubMed  Google Scholar 

  • Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ et al (2014) Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121(10):1904–1914

    Article  PubMed  Google Scholar 

  • Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J et al (2012) Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 119(10):2125–2132

    Article  PubMed  Google Scholar 

  • Chang-Lin JE, Burke JA, Peng Q, Lin T, Orilla WC, Ghosn CR et al (2011) Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes. Invest Ophthalmol Vis Sci 52(7):4605–4609

    Article  CAS  PubMed  Google Scholar 

  • Diabetic Retinopathy Clinical Research Network (2008) A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115(9):1447–9, 1449.e1–10

    Google Scholar 

  • Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB et al (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117(6):1064–1077.e35

    Google Scholar 

  • Ding X, Patel M, Chan CC (2009) Molecular pathology of age-related macular degeneration. Prog Retin Eye Res 28(1):1–18

    Article  CAS  PubMed  Google Scholar 

  • Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM et al (2011) Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 118(4):609–614

    Article  PubMed  PubMed Central  Google Scholar 

  • Felinski EA, Antonetti DA (2005) Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy. Curr Eye Res 30(11):949–957

    Article  CAS  PubMed  Google Scholar 

  • Garcia Filho CA, Yehoshua Z, Gregori G, Nunes RP, Penha FM, Moshfeghi AA et al (2014) Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina 45(1):18–31

    PubMed  Google Scholar 

  • Gillies MC, Lim LL, Campain A, Quin GJ, Salem W, Li J et al (2014) A randomized clinical trial of intravitreal bevacizumab versus intravitreal dexamethasone for diabetic macular edema: the BEVORDEX study. Ophthalmology 121(12):2473–2481

    Article  PubMed  Google Scholar 

  • Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 20(6):705–732

    Article  CAS  PubMed  Google Scholar 

  • Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J et al (2010) Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 117(6):1134–1146.e3

    Article  PubMed  Google Scholar 

  • Hashizume K, Hirasawa M, Imamura Y, Noda S, Shimizu T, Shinoda K et al (2008) Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. Am J Pathol 172(5):1325–1331

    Article  PubMed  PubMed Central  Google Scholar 

  • http://www.ophthotech.com/product-candidates/. Accessed 18 April 2016

  • http://www.roche.com/investors/updates/inv-update-2013-08-27.htm. Accessed 18 April 2016

  • Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M et al (2009) A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch Ophthalmol 127(9):1101–1114

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuppermann BD, Goldstein M, Maturi RK, Pollack A, Singer M, Tufail A et al (2015) Dexamethasone intravitreal implant as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration: a multicenter randomized controlled trial. Ophthalmologica 234(1):40–54

    Article  CAS  PubMed  Google Scholar 

  • Lee WJ, Kang MH, Seong M, Cho HY (2012) Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion. Br J Ophthalmol 96(11):1426–1430

    Article  PubMed  Google Scholar 

  • Maturi RK, Bleau L, Saunders J, Mubasher M, Stewart MW (2015) A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the efficacy of the dexamethasone-delayed delivery system as an adjunct to bevacizumab compared with continued bevacizumab monotherapy. Retina 35(8):1604–1614

    Article  CAS  PubMed  Google Scholar 

  • Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T et al (2005) Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol 140(2):256–261

    Article  CAS  PubMed  Google Scholar 

  • Ozaki E, Campbell M, Kiang AS, Humphries M, Doyle SL, Humphries P (2014) Inflammation in age-related macular degeneration. Adv Exp Med Biol 801:229–235

    Article  PubMed  Google Scholar 

  • Ranchod TM, Ray SK, Daniels SA, Leong CJ, Ting TD, Verne AZ (2013) LuceDex: a prospective study comparing ranibizumab plus dexamethasone combination therapy versus ranibizumab monotherapy for neovascular age-related macular degeneration. Retina 33(8):1600–1604

    Article  CAS  PubMed  Google Scholar 

  • Scott IU, Ip MS, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M et al (2009) A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol 127(9):1115–1128

    Article  PubMed  PubMed Central  Google Scholar 

  • Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F et al (2005) Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci 46(4):1440–1444

    Article  PubMed  Google Scholar 

  • Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitcup SM, Sodhi A, Atkinson JP, Holers VM, Sinha D, Rohrer B et al (2013a) The role of the immune response in age-related macular degeneration. Int J Inflamm 2013:348092

    Google Scholar 

  • Whitcup SM, Nussenblatt RB, Lightman SL, Hollander DA (2013b) Inflammation in retinal disease. Int J Inflamm 2013:724648

    Google Scholar 

  • Xu H, Chen M, Forrester JV (2009) Para-inflammation in the aging retina. Prog Retin Eye Res 28(5):348–368

    Article  PubMed  Google Scholar 

  • Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, Gregori G, Penha FM, Moshfeghi AA et al (2014) Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology 121(3):693–701

    Article  PubMed  Google Scholar 

  • Zhao Z, Chen Y, Wang J, Sternberg P, Freeman ML, Grossniklaus HE et al (2011) Age-related retinopathy in NRF2-deficient mice. PLoS One 6(4):e19456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhioua I, Semoun O, Lalloum F, Souied EH (2015) Intravitreal dexamethasone implant in patients with ranibizumab persistent diabetic macular edema. Retina 35(7):1429–1435

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Baruch D. Kuppermann .

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Narayanan, R., Kuppermann, B.D. (2016). Corticosteroids and Anti-Complement Therapy in Retinal Diseases. In: Whitcup, S., Azar, D. (eds) Pharmacologic Therapy of Ocular Disease. Handbook of Experimental Pharmacology, vol 242. Springer, Cham. https://doi.org/10.1007/164_2016_22

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